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1. Rapid decrease in IL-1Ra and IP-10 plasma levels following tuberculosis treatment initiation

Author: Polidy Pean, Roseline Affi, Corine Chazalon, Ben Cheick Soumahoro, Delphine Gabillard, Bunnet Dim, Laurence Borand, Raoul Moh, Xavier Anglaret, François-Xavier Blanc, Pierre-Marie Girard, Guislaine Carcelain, Didier Laureillard, and Laurence Weiss
Subjects: Tuberculosis, HIV, Biomarkers, Treatment response, Infectious and parasitic diseases, RC109-216
Abstract: Objectives: Monitoring tools that could provide quick predictions of tuberculosis (TB) treatment outcomes are urgently needed. Here, we assessed whether the evolution of selected biomarkers of innate immunity may help monitoring TB treatment response within 2 weeks of treatment initiation. Methods: ANRS12394-LILAC-TB was a proof-of-concept prospective study: adults with a rifampicin-susceptible TB who are HIV-negative and HIV-infected documented by a positive Xpert MTB/RIF test were enrolled in Cambodia and Côte d'Ivoire. Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interferon-γ–induced protein-10 and clusters of differentiation (CD) (scavenging CD163) were measured by commercial enzyme-linked immunosorbent assay kits. A Wilcoxon test for paired data was used for longitudinal comparisons. Results: A total of 55 patients were enrolled (women: 31%, median age: 37 years; median CD4 count in the 10 of 13 participants with HIV: 53 cells/mm3). Overall, 83% were considered in TB treatment success. Compared with baseline, the IL-1Ra plasma levels significantly decreased as soon as week (W) 1, independent of HIV status (−71% in HIV-positive vs −33% in HIV-negative; P
Published: 2024
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2. Inappropriate antibiotic prescribing and its determinants among outpatient children in 3 low- and middle-income countries: A multicentric community-based cohort study.

Author: Antoine Ardillon, Lison Ramblière, Elsa Kermorvant-Duchemin, Touch Sok, Andrianirina Zafitsara Zo, Jean-Baptiste Diouf, Pring Long, Siyin Lach, Fatoumata Diene Sarr, Laurence Borand, Felix Cheysson, Jean-Marc Collard, Perlinot Herindrainy, Agathe de Lauzanne, Muriel Vray, Elisabeth Delarocque-Astagneau, Didier Guillemot, Bich-Tram Huynh, and BIRDY study group
Subjects: Medicine
Abstract: BackgroundAntibiotic resistance is a global public health issue, particularly in low- and middle-income countries (LMICs), where antibiotics required to treat resistant infections are not affordable. LMICs also bear a disproportionately high burden of bacterial diseases, particularly among children, and resistance jeopardizes progress made in these areas. Although outpatient antibiotic use is a major driver of antibiotic resistance, data on inappropriate antibiotic prescribing in LMICs are scarce at the community level, where the majority of prescribing occurs. Here, we aimed to characterize inappropriate antibiotic prescribing among young outpatient children and to identify its determinants in 3 LMICs.Methods and findingsWe used data from a prospective, community-based mother-and-child cohort (BIRDY, 2012 to 2018) conducted across urban and rural sites in Madagascar, Senegal, and Cambodia. Children were included at birth and followed-up for 3 to 24 months. Data from all outpatient consultations and antibiotics prescriptions were recorded. We defined inappropriate prescriptions as antibiotics prescribed for a health event determined not to require antibiotic therapy (antibiotic duration, dosage, and formulation were not considered). Antibiotic appropriateness was determined a posteriori using a classification algorithm developed according to international clinical guidelines. We used mixed logistic analyses to investigate risk factors for antibiotic prescription during consultations in which children were determined not to require antibiotics. Among the 2,719 children included in this analysis, there were 11,762 outpatient consultations over the follow-up period, of which 3,448 resulted in antibiotic prescription. Overall, 76.5% of consultations resulting in antibiotic prescription were determined not to require antibiotics, ranging from 71.5% in Madagascar to 83.3% in Cambodia. Among the 10,416 consultations (88.6%) determined not to require antibiotic therapy, 25.3% (n = 2,639) nonetheless resulted in antibiotic prescription. This proportion was much lower in Madagascar (15.6%) than in Cambodia (57.0%) or Senegal (57.2%) (p < 0.001). Among the consultations determined not to require antibiotics, in both Cambodia and Madagascar the diagnoses accounting for the greatest absolute share of inappropriate prescribing were rhinopharyngitis (59.0% of associated consultations in Cambodia, 7.9% in Madagascar) and gastroenteritis without evidence of blood in the stool (61.6% and 24.6%, respectively). In Senegal, uncomplicated bronchiolitis accounted for the greatest number of inappropriate prescriptions (84.4% of associated consultations). Across all inappropriate prescriptions, the most frequently prescribed antibiotic was amoxicillin in Cambodia and Madagascar (42.1% and 29.2%, respectively) and cefixime in Senegal (31.2%). Covariates associated with an increased risk of inappropriate prescription include patient age greater than 3 months (adjusted odds ratios (aOR) with 95% confidence interval (95% CI) ranged across countries from 1.91 [1.63, 2.25] to 5.25 [3.85, 7.15], p < 0.001) and living in rural as opposed to urban settings (aOR ranged across countries from 1.83 [1.57, 2.14] to 4.40 [2.34, 8.28], p < 0.001). Diagnosis with a higher severity score was also associated with an increased risk of inappropriate prescription (aOR = 2.00 [1.75, 2.30] for moderately severe, 3.10 [2.47, 3.91] for most severe, p < 0.001), as was consultation during the rainy season (aOR = 1.32 [1.19, 1.47], p < 0.001). The main limitation of our study is the lack of bacteriological documentation, which may have resulted in some diagnosis misclassification and possible overestimation of inappropriate antibiotic prescription.ConclusionIn this study, we observed extensive inappropriate antibiotic prescribing among pediatric outpatients in Madagascar, Senegal, and Cambodia. Despite great intercountry heterogeneity in prescribing practices, we identified common risk factors for inappropriate prescription. This underscores the importance of implementing local programs to optimize antibiotic prescribing at the community level in LMICs.
Published: 2023
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3. Simplified Criteria to Assess Long-Term Antiviral Treatment Indication in Chronic HBV-Infected Pregnant Women in Cambodia

Author: Jee-Seon Yang, Saren Sovann, Yusuke Shimakawa, Sovann Nhoueng, Bunnet Dim, Chanlina Vong, Channa Sann, Julia Guillebaud, Darapolin Vann, Bunrith Touch, Hyna Chea, Wathanak Pisey Choupoan Phirum, Eric Rosenthal, Christelle Paul, Leangchhun Khun, Chantana Yay, Denis Laurent, Samsorphea Chhun, Laurence Borand, and Olivier Segeral
Subjects: hepatitis B, pregnancy, postpartum, long-term treatment, public health, international guidelines, Microbiology, QR1-502
Abstract: Pregnant women identified to carry hepatitis B surface antigen (HBsAg) should be linked to care for the determination of the need for long-term antiviral therapy (LTT). We assessed the performance of simplified criteria, free from HBV DNA quantification, to select women eligible for LTT using different international guidelines as a reference. A retrospective analysis of HBV-infected pregnant women enrolled in the phase 4 ANRS TA-PROHM study was conducted in Cambodia. Sensitivity, specificity, and AUROC were computed to compare three simplified criteria (TREAT-B, HBcrAg/ALT, and TA-PROHM) with the American (AASLD) and European (EASL) guidelines as a reference. An additional assessment was performed at 6 months postpartum. Of 651 HBsAg-positive women, 209 (32%) received peripartum antiviral prophylaxis using tenofovir disoproxil fumarate (TDF). During pregnancy, 9% and 12% of women were eligible for LTT according to AASLD and EASL guidelines, respectively; 21% and 24% of women were eligible for prophylactic TDF and 2% and 5% in those ineligible (p < 0.001). Using the AASLD guidelines, the AUROC of TREAT-B, HBcrAg/ALT, and TA-PROHM scores were 0.88 (95%CI, 0.85–0.90), 0.90 (95%CI, 0.87–0.92), and 0.76 (95%CI, 0.73–0.80), respectively. Using the EASL guidelines, the AUROCs were lower: 0.73 (95%CI, 0.69–0.76), 0.76 (95%CI, 0.73–0.80), and 0.71 (95%CI, 0.67–0.74), respectively. Among those ineligible for prophylactic TDF, only 2% to 6% present an indication for LTT at 24 weeks postpartum. Few pregnant women are eligible for LTT, and the use of simplified criteria could represent an efficient triage option in decentralized areas to identify those negative for whom there is no urgent indication for LTT and focus on those positive for whom other exams must be conducted to confirm LTT indication.
Published: 2024
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4. Natural Killer Repertoire Restoration in TB/HIV Co-Infected Individuals Experienced an Immune Reconstitution Syndrome (CAMELIA Trial, ANRS 12153)

Author: Polidy Pean, Yoann Madec, Eric Nerrienet, Laurence Borand, Didier Laureillard, Marcelo Fernandez, Olivier Marcy, and Daniel Scott-Algara
Subjects: HIV, tuberculosis, NK cells, antiretroviral treatment, immune reconstitution, immune reconstitution inflammatory syndrome, Medicine
Abstract: IRIS is a common complication in HIV-infected patients treated for tuberculosis (TB) and cART. Our aim was to evaluate NK cell reconstitution in HIV-infected patients with TB-IRIS compared to those without IRIS. 147 HIV-infected patients with TB from the CAMELIA trial were enrolled. HIV+TB+ patients were followed for 32 weeks. The NK cell repertoire was assessed in whole blood at different time points. As CAMELIA has two arms (early and late cART initiation), we analysed them separately. At enrolment, individuals had low CD4 cell counts (27 cells/mm3) and high plasma viral loads (5.76 and 5.50 log/mL for IRIS and non-IRIS individuals, respectively). Thirty-seven people developed IRIS (in the early and late arms). In the early and late arms, we observed similar proportions of total NK and NK cell subsets in TB-IRIS and non-IRIS individuals during follow-up, except for the CD56dimCD16pos (both arms) and CD56dimCD16neg (late arm only) subsets, which were higher in TB-IRIS and non-IRIS individuals, respectively, after cART. Regarding the repertoire and markers of NK cells, significant differences (lower expression of NKp30, NKG2A (CD159a), NKG2D (CD314) were observed in TB-IRIS compared to non-IRIS individuals after the start of cART. In the late arm, some changes (increased expression of CD69, NKG2C, CD158i) were observed in TB-IRIS compared to non-IRIS individuals, but only before cART initiation (during TB treatment). KIR expression by NK cells (CD158a and CD158i) was similar in both groups. CD69 expression by NK cells decreased in all groups. Expression of the NCR repertoire (NKp30, NKp44, NKp46) has similar kinetics in TB-IRIS subjects compared to non-IRIS subjects regardless of the arm analysed. NK cell reconstitution appeared to be better in TB-IRIS subjects. Although NK cell reconstitution is impaired in HIV infection after cART, as previously reported, it does not appear to be affected by the development of IRIS in HIV and TB-infected individuals.
Published: 2023
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5. Acceptability of decentralizing childhood tuberculosis diagnosis in low-income countries with high tuberculosis incidence: Experiences and perceptions from health care workers in Sub-Saharan Africa and South-East Asia.

Author: Basant Joshi, Yara Voss De Lima, Douglas Mbang Massom, Sanary Kaing, Marie-France Banga, Egerton Tamba Kamara, Sheriff Sesay, Laurence Borand, Jean-Voisin Taguebue, Raoul Moh, Celso Khosa, Guillaume Breton, Juliet Mwanga-Amumpaire, Maryline Bonnet, Eric Wobudeya, Olivier Marcy, Joanna Orne-Gliemann, and TB-Speed Decentralization study group
Subjects: Public aspects of medicine, RA1-1270
Abstract: Decentralizing childhood tuberculosis services, including diagnosis, is now recommended by the WHO and could contribute to increasing tuberculosis detection in high burden countries. However, implementing microbiological tests and clinical evaluation could be challenging for health care workers (HCWs) in Primary Health Centers (PHCs) and even District Hospitals (DHs). We sought to assess the acceptability of decentralizing a comprehensive childhood tuberculosis diagnosis package from HCWs' perspective. We conducted implementation research nested within the TB-Speed Decentralization study. HCWs from two health districts of Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone, and Uganda implemented systematic screening, nasopharyngeal aspirates (NPA) and stool sample collection with molecular testing, clinical evaluation and chest X-ray (CXR) interpretation. We investigated their experiences and perceptions in delivering the diagnostic package components in 2020-21 using individual semi-structured interviews. We conducted thematic analysis, supported by the Theoretical Framework of Acceptability. HCWs (n = 130, 55% female, median age 36 years, 53% nurses, 72% PHC-based) perceived that systematic screening, although increasing workload, was beneficial as it improved childhood tuberculosis awareness. Most HCWs shared satisfaction and confidence in performing NPA, despite procedure duration, need to involve parents/colleagues and discomfort for children. HCWs shared positive attitudes towards stool sample-collection but were frustrated by delayed stool collection associated with cultural practices, transport and distance challenges. Molecular testing, conducted by nurses or laboratory technicians, was perceived as providing quality results, contributing to diagnosis. Clinical evaluation and diagnosis raised self-efficacy issues and need for continuous training and clinical mentoring. HCWs valued CXR, however complained that technical and logistical problems limited access to digital reports. Referral from PHC to DH was experienced as burdensome. HCWs at DH and PHC-levels perceived and experienced decentralized childhood tuberculosis diagnosis as acceptable. Implementation however could be hampered by feasibility issues, and calls for innovative referral mechanisms for patients, samples and CXR.
Published: 2023
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6. Circulation of Bordetella pertussis in vaccinated Cambodian children: A transversal serological study

Author: Gaelle Noel, Laurence Borand, Chanthy Leng, Chanthy Keang, Chhunly Botr, Bunnet Dim, Alexandra Kerleguer, Yik S. Peng, Navin Sreng, Vichit Ork, Mohand Ait-Ahmed, Nicole Guiso, and Fabien Taieb
Subjects: Pertussis, Cambodia, Whole-cell vaccine, Sero-prevalence, Timeliness, Infectious and parasitic diseases, RC109-216
Abstract: Background: The Cambodia pertussis immunization schedule includes three doses given at age 6, 10 and 14 weeks using a whole-pertussis vaccine. No booster doses are included. Pertussis biological diagnosis is unavailable in Cambodia and its burden remains unclear. This study aimed to provide accurate data on pertussis serological status of Cambodian children and adolescents, and to evaluate vaccination timeliness. Methods: Fully vaccinated children aged 3–15 years were recruited at the Rabies Prevention Center, Institut Pasteur in Cambodia, Phnom Penh. Capillary blood samples and information on pertussis vaccination history were collected. Anti-pertussis toxin (PT) IgG titers were quantified by ELISA. Results: Compliance with the national immunization schedule was 95.1%. Initiation of vaccination after 8 weeks of age was observed for 29.0% of the children, but was less frequent in the youngest children (13.0%) compared with the oldest ones (46.4%). Rate of children exhibiting anti-PT IgG varied across age groups, and increased from 35.7% to 55.0% in 3–5 and 12–15 years age groups, respectively. Conclusion: Pertussis circulates among vaccinated Cambodian children and adolescents. These data support the need for public health authorities to strengthen pertussis surveillance and use local epidemiological data to make evidence-based decision for the establishment of an optimal vaccination strategy.
Published: 2021
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7. Impact of systematic early tuberculosis detection using Xpert MTB/RIF Ultra in children with severe pneumonia in high tuberculosis burden countries (TB-Speed pneumonia): a stepped wedge cluster randomized trial

Author: Aurélia Vessière, Hélène Font, Delphine Gabillard, Laurence Adonis-Koffi, Laurence Borand, Chishala Chabala, Celso Khosa, Sandra Mavale, Raoul Moh, Veronica Mulenga, Juliet Mwanga-Amumpere, Jean-Voisin Taguebue, Mao Tan Eang, Christophe Delacourt, James A. Seddon, Manon Lounnas, Sylvain Godreuil, Eric Wobudeya, Maryline Bonnet, and Olivier Marcy
Subjects: Children, Pneumonia, Tuberculosis, Nasopharyngeal aspirate, Stool, Xpert MTB/RIF ultra, Pediatrics, RJ1-570
Abstract: Abstract Background In high tuberculosis (TB) burden settings, there is growing evidence that TB is common in children with pneumonia, the leading cause of death in children under 5 years worldwide. The current WHO standard of care (SOC) for young children with pneumonia considers a diagnosis of TB only if the child has a history of prolonged symptoms or fails to respond to antibiotic treatments. As a result, many children with TB-associated severe pneumonia are currently missed or diagnosed too late. We therefore propose a diagnostic trial to assess the impact on mortality of adding the systematic early detection of TB using Xpert MTB/RIF Ultra (Ultra) performed on nasopharyngeal aspirates (NPA) and stool samples to the WHO SOC for children with severe pneumonia, followed by immediate initiation of anti-TB treatment in children testing positive on any of the samples. Methods TB-Speed Pneumonia is a pragmatic stepped-wedge cluster randomized controlled trial conducted in six countries with high TB incidence rate (Côte d’Ivoire, Cameroon, Uganda, Mozambique, Zambia and Cambodia). We will enrol 3780 children under 5 years presenting with WHO-defined severe pneumonia across 15 hospitals over 18 months. All hospitals will start managing children using the WHO SOC for severe pneumonia; one hospital will be randomly selected to switch to the intervention every 5 weeks. The intervention consists of the WHO SOC plus rapid TB detection on the day of admission using Ultra performed on 1 nasopharyngeal aspirate and 1 stool sample. All children will be followed for 3 months, with systematic trial visits at day 3, discharge, 2 weeks post-discharge, and week 12. The primary endpoint is all-cause mortality 12 weeks after inclusion. Qualitative and health economic evaluations are embedded in the trial. Discussion In addition to testing the main hypothesis that molecular detection and early treatment will reduce TB mortality in children, the strength of such pragmatic research is that it provides some evidence regarding the feasibility of the intervention as part of routine care. Should this intervention be successful, safe and well tolerated, it could be systematically implemented at district hospital level where children with severe pneumonia are referred. Trial registration ClinicalTrials.gov, NCT03831906 . Registered 6 February 2019.
Published: 2021
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8. Klebsiella pneumoniae carriage in low-income countries: antimicrobial resistance, genomic diversity and risk factors

Author: Bich-Tram Huynh, Virginie Passet, Andriniaina Rakotondrasoa, Thierno Diallo, Alexandra Kerleguer, Melanie Hennart, Agathe De Lauzanne, Perlinot Herindrainy, Abdoulaye Seck, Raymond Bercion, Laurence Borand, Maria Pardos de la Gandara, Elisabeth Delarocque-Astagneau, Didier Guillemot, Muriel Vray, Benoit Garin, Jean-Marc Collard, Carla Rodrigues, and Sylvain Brisse
Subjects: klebsiella pneumoniae, carriage, antibiotic resistance, genomic diversity, community, low-income countries, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background: Klebsiella pneumoniae (hereafter, Kp) is a major public health threat responsible for high levels of multidrug resistant (MDR) human infections. Besides, Kp also causes severe infections in the community, especially in Asia and Africa. Although most Kp infections are caused by endogenous intestinal carriage, little is known about the prevalence and microbiological characteristics of Kp in asymptomatic human carriage, and attached risk factors including environmental sources exposure. Methods: Here, 911 pregnant women from communities in Madagascar, Cambodia, and Senegal were screened for gut colonization by Kp. Characteristics of Kp strains (antimicrobial susceptibility, genomic diversity, virulence, and resistance genes) were defined, and associated risk factors were investigated. Results: Kp carriage rate was 55.9%, and Kp populations were highly heterogeneous (6 phylogroups, 325 sequence types, Simpson index 99.6%). One third of Kp isolates had acquired antimicrobial resistance genes. MDR-Kp (11.7% to 39.7%) and extended spectrum beta-lactamase (ESBL)-producing Kp (0.7% to 14.7%) varied among countries. Isolates with virulence genes were detected (14.5%). Environmental exposure factors including food, animal contacts, or hospitalization of household members were associated with carriage of Kp, antimicrobial resistance and hypervirulence. However, risk factors were country-specific and Kp subpopulation-specific. Conclusion: This large-scale multicenter study uncovers the huge diversity of Kp in human gut carriage, demonstrates that antimicrobial resistance is widespread in communities of three low-income countries, and underlines the challenges posed by Kp colonization to the control of antimicrobial resistance.
Published: 2020
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9. Severe bacterial neonatal infections in Madagascar, Senegal, and Cambodia: A multicentric community-based cohort study.

Author: Bich-Tram Huynh, Elsa Kermorvant-Duchemin, Rattanak Chheang, Frederique Randrianirina, Abdoulaye Seck, Elisoa Hariniaina Ratsima, Zafitsara Zo Andrianirina, Jean-Baptiste Diouf, Armya Youssouf Abdou, Sophie Goyet, Véronique Ngo, Siyin Lach, Long Pring, Touch Sok, Michael Padget, Fatoumata Diene Sarr, Laurence Borand, Benoit Garin, Jean-Marc Collard, Perlinot Herindrainy, Agathe de Lauzanne, Muriel Vray, Elisabeth Delarocque-Astagneau, Didier Guillemot, and BIRDY study group
Subjects: Medicine
Abstract: BackgroundSevere bacterial infections (SBIs) are a leading cause of neonatal deaths in low- and middle-income countries (LMICs). However, most data came from hospitals, which do not include neonates who did not seek care or were treated outside the hospital. Studies from the community are scarce, and few among those available were conducted with high-quality microbiological techniques. The burden of SBI at the community level is therefore largely unknown. We aimed here to describe the incidence, etiology, risk factors, and antibiotic resistance profiles of community-acquired neonatal SBI in 3 LMICs.Methods and findingsThe BIRDY study is a prospective multicentric community-based mother and child cohort study and was conducted in both urban and rural areas in Madagascar (2012 to 2018), Cambodia (2014 to 2018), and Senegal (2014 to 2018). All pregnant women within a geographically defined population were identified and enrolled. Their neonates were actively followed from birth to 28 days to document all episodes of SBI. A total of 3,858 pregnant women (2,273 (58.9%) in Madagascar, 814 (21.1%) in Cambodia, and 771 (20.0%) in Senegal) were enrolled in the study, and, of these, 31.2% were primigravidae. Women enrolled in the urban sites represented 39.6% (900/2,273), 45.5% (370/814), and 61.9% (477/771), and those enrolled in the rural sites represented 60.4% (1,373/2,273), 54.5% (444/814), and 38.1% (294/771) of the total in Madagascar, Cambodia, and Senegal, respectively. Among the 3,688 recruited newborns, 49.6% were male and 8.7% were low birth weight (LBW). The incidence of possible severe bacterial infection (pSBI; clinical diagnosis based on WHO guidelines of the Integrated Management of Childhood Illness) was 196.3 [95% confidence interval (CI) 176.5 to 218.2], 110.1 [88.3 to 137.3], and 78.3 [59.5 to 103] per 1,000 live births in Madagascar, Cambodia, and Senegal, respectively. The incidence of pSBI differed between urban and rural sites in all study countries. In Madagascar, we estimated an incidence of 161.0 pSBI per 1,000 live births [133.5 to 194] in the urban site and 219.0 [192.6 to 249.1] pSBI per 1,000 live births in the rural site (p = 0.008). In Cambodia, estimated incidences were 141.1 [105.4 to 189.0] and 85.3 [61.0 to 119.4] pSBI per 1,000 live births in urban and rural sites, respectively (p = 0.025), while in Senegal, we estimated 103.6 [76.0 to 141.2] pSBI and 41.5 [23.0 to 75.0] pSBI per 1,000 live births in urban and rural sites, respectively (p = 0.006). The incidences of culture-confirmed SBI were 15.2 [10.6 to 21.8], 6.5 [2.7 to 15.6], and 10.2 [4.8 to 21.3] per 1,000 live births in Madagascar, Cambodia, and Senegal, respectively, with no difference between urban and rural sites in each country. The great majority of early-onset infections occurred during the first 3 days of life (72.7%). The 3 main pathogens isolated were Klebsiella spp. (11/45, 24.4%), Escherichia coli (10/45, 22.2%), and Staphylococcus spp. (11/45, 24.4%). Among the 13 gram-positive isolates, 5 were resistant to gentamicin, and, among the 29 gram-negative isolates, 13 were resistant to gentamicin, with only 1 E. coli out of 10 sensitive to ampicillin. Almost one-third of the isolates were resistant to both first-line drugs recommended for the management of neonatal sepsis (ampicillin and gentamicin). Overall, 38 deaths occurred among neonates with SBI (possible and culture-confirmed SBI together). LBW and foul-smelling amniotic fluid at delivery were common risk factors for early pSBI in all 3 countries. A main limitation of the study was the lack of samples from a significant proportion of infants with pBSI including 35 neonatal deaths. Without these samples, bacterial infection and resistance profiles could not be confirmed.ConclusionsIn this study, we observed a high incidence of neonatal SBI, particularly in the first 3 days of life, in the community of 3 LMICs. The current treatment for the management of neonatal infection is hindered by antimicrobial resistance. Our findings suggest that microbiological diagnosis of SBI remains a challenge in these settings and support more research on causes of neonatal death and the implementation of early interventions (e.g., follow-up of at-risk newborns during the first days of life) to decrease the burden of neonatal SBI and associated mortality and help achieve Sustainable Development Goal 3.
Published: 2021
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10. Diagnosis and management of latent tuberculosis infection in Asia: Review of current status and challenges

Author: Nicholas I. Paton, Laurence Borand, Jubert Benedicto, Mar Mar Kyi, Asif Mujtaba Mahmud, Mohd Nor Norazmi, Nandini Sharma, Charoen Chuchottaworn, Yi-Wen Huang, Nastiti Kaswandani, Hoi Le Van, Grace C.Y. Lui, and Tan Eang Mao
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Asia has the highest burden of tuberculosis (TB) and latent TB infection (LTBI) in the world. Optimizing the diagnosis and treatment of LTBI is one of the key strategies for achieving the WHO ‘End TB’ targets. We report the discussions from the Asia Latent TubERculosis (ALTER) expert panel meeting held in 2018 in Singapore. In this meeting, a group of 13 TB experts from Bangladesh, Cambodia, Hong Kong, India, Indonesia, Malaysia, Myanmar, the Philippines, Singapore, Taiwan, Thailand and Vietnam convened to review the literature, discuss the barriers and propose strategies to improve the management of LTBI in Asia. Strategies for the optimization of risk group prioritization, diagnosis, treatment, and research of LTBI are reported. The perspectives presented herein, may help national programs and professional societies of the respective countries enhance the adoption of the WHO guidelines, scale-up the implementation of national guidelines based on the regional needs, and provide optimal guidance to clinicians for the programmatic management of LTBI. Keywords: Latent tuberculosis infection, Asia, Awareness, Optimization
Published: 2019
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11. Meat and Fish as Sources of Extended-Spectrum β-Lactamase–Producing Escherichia coli, Cambodia

Author: Maya Nadimpalli, Yith Vuthy, Agathe de Lauzanne, Laetitia Fabre, Alexis Criscuolo, Malika Gouali, Bich-Tram Huynh, Thierry Naas, Thong Phe, Laurence Borand, Jan Jacobs, Alexandra Kerléguer, Patrice Piola, Didier Guillemot, Simon Le Hello, and Elisabeth Delarocque-Astagneau
Subjects: ESBL, antibiotic resistance, food safety, lower- and middle-income countries, Southeast Asia, Escherichia coli, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: We compared extended-spectrum β-lactamase–producing Escherichia coli isolates from meat and fish, gut-colonized women, and infected patients in Cambodia. Nearly half of isolates from women were phylogenetically related to food-origin isolates; a subset had identical multilocus sequence types, extended-spectrum β-lactamase types, and antimicrobial resistance patterns. Eating sun-dried poultry may be an exposure route.
Published: 2019
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12. High Activation of γδ T Cells and the γδ2pos T-Cell Subset Is Associated With the Onset of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome, ANRS 12153 CAPRI NK

Author: Polidy Pean, Janin Nouhin, Meng Ratana, Yoann Madec, Laurence Borand, Olivier Marcy, Didier Laureillard, Marcelo Fernandez, Françoise Barré-Sinoussi, Laurence Weiss, and Daniel Scott-Algara
Subjects: HIV, tuberculosis, immune reconstitution inflammatory syndrome, gamma delta T cells, invariant NKT cells, Immunologic diseases. Allergy, RC581-607
Abstract: Background: Human Immunodeficiency Virus 1 (HIV-1) and Mycobacterium Tuberculosis (Mtb) co-infected patients are commonly at risk of immune reconstitution inflammatory syndrome (IRIS) when initiating antiretroviral treatment (ART). Evidence indicates that innate immunity plays a role in TB-IRIS. Here, we evaluate the phenotype of Gamma-delta (γδ) T cells and invariant Natural Killer (iNK) T cells in tuberculosis-associated IRIS.Methods: Forty-eight HIV+/TB+ patients (21 IRIS) and three control groups: HIV–/TB– (HD, n = 11), HIV+/TB– (n = 26), and HIV–/TB+ (n = 22) were studied. Samples were taken at ART initiation (week 2 of anti-tuberculosis treatment) and at the diagnosis of IRIS for HIV+/TB+; before ART for HIV+/TB-, and at week 2 of anti-tuberculosis treatment for HIV–/TB+ patients. γδ T cells and Invariant natural killer T (iNKT) cells were analyzed by flow cytometry.Results: Before ART, IRIS, and non-IRIS patients showed a similar proportion of γδpos T and iNKT cells. HLA-DR on γδpos T cells and δ2posγδpos T cells was significantly higher in TB-IRIS vs. non-IRIS patients and controls (p < 0.0001). NKG2D expression on γδpos T cells and the δ2posγδpos T cell subset was lower in HIV+/TB+ patients than controls. CD158a expression on γδpos T cells was higher in TB-IRIS than non-IRIS (p = 0.02), HIV+/TB–, and HIV–/TB- patients.Conclusion: The higher activation of γδposT cells and the γδ2posγδpos T cell subset suggests that γδ T cells may play a role in the pathogenesis of TB-IRIS.
Published: 2019
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13. Plasma concentrations, efficacy and safety of efavirenz in HIV-infected adults treated for tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA trial).

Author: Laurence Borand, Yoann Madec, Didier Laureillard, Monidarin Chou, Olivier Marcy, Phearavin Pheng, Narom Prak, Chindamony Kim, Khemarin Kim Lak, Chanroeun Hak, Bunnet Dim, Eric Nerrienet, Arnaud Fontanet, Thim Sok, Anne E Goldfeld, François-Xavier Blanc, and Anne-Marie Taburet
Subjects: Medicine, Science
Abstract: ObjectiveTo assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients.MethodsHIV-infected adults with CD4+ T cell count ≤ 200/mm(3) received standard 6-month tuberculosis treatment and antiretroviral therapy including a daily-dose of 600 mg of efavirenz, irrespective of their body weight. Mid-dose blood samples were drawn both on tuberculosis treatment (week +2 and week +6 after antiretroviral therapy initiation, and week 22 of follow-up) and off tuberculosis treatment (week 50 of follow-up). Considered therapeutic range was 1,000 to 4,000 ng/mL. Multivariate analysis was performed to evaluate the association between efavirenz concentration below 1,000 ng/mL and virological failure. Linear regression was used to test the association between efavirenz exposure and CD4+ T cell gain. Severe side effects potentially related to efavirenz were described and their association with efavirenz exposure was tested by multivariate analysis.ResultsEfavirenz plasma concentrations were available in 540 patients. Median [interquartile range] efavirenz concentrations were 2,674 ng/mL [1,690-4,533], 2,667 ng/mL [1,753-4,494] and 2,799 ng/mL [1,804-4,744] at week +2, week +6, week 22, respectively, and 2,766 ng/mL [1,941-3,976] at week 50. Efavirenz concentrations were lower at week 50 (off rifampicin) compared to week 22 (on rifampicin) (pConclusionBody weight and tuberculosis treatment were not associated with low efavirenz concentrations or treatment failure, supporting the 600 mg daily-dose of efavirenz in HIV-tuberculosis co-infected patients. High efavirenz concentrations were related to a higher risk of central nervous system side effects and hepatotoxicity.Trial registrationClinicalTrials.gov NCT01300481.
Published: 2014
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14. Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam.

Author: Nguyen Thi Ngoc Lan, Nguyen Thi Nguyet Thu, Aurélie Barrail-Tran, Nguyen Hong Duc, Nguyen Ngoc Lan, Didier Laureillard, Truong Thi Xuan Lien, Laurence Borand, Catherine Quillet, Catherine Connolly, Dominique Lagarde, Alexander Pym, Christian Lienhardt, Nguyen Huy Dung, Anne-Marie Taburet, and Anthony D Harries
Subjects: Medicine, Science
Abstract: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured.This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir.Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 - 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations.Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis.ClinicalTrials.gov NCT00651066.
Published: 2014
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15. Effect of decentralising childhood tuberculosis diagnosis to primary health centre versus district hospital levels on disease detection in children from six high tuberculosis incidence countries: an operational research, pre-post intervention study

Author: Laurence, Borand, Agathe, de Lauzanne, Bunnet, Dim, Seyla, Heang, Sanary, Kaing, Chanty, Keang, Socheat, L.Y., Pichpiseth, Meas, Sovann, Nhoueng, Long, Pring, Vouchleang, Sreng, Song, Yin, Saren, Sovan, Chanvirak, Phan, Chanra, Chreng, Ratha, Khoun, Monicando, Rin, Sophea, Pal, Boraneath, Nang, Rathakrun, Pom, Tan Eang, Mao, Simoy, Chhim, Huot, Touch, Kosal, Suon, Saronn, Chum, Kimhong, Tok, Kimchorn, Pring, Satya, Krouch, Chean, Chok, Sunleng, Seun, Savtey, Phon, Mai, Nang, Kimda, Hun, Vanny, Hong, Dara, Sok, Kosal, Chea, Bunthoeun, Chheang, Rino, Sem, Lam, Lay, Haysan, Say, Pholly, Kem, Sreyphal, Meng, Sokheng, Phorn, Sreyvann, Him, Peakdey, Pheach, Dalai, Kive, Moeur, Sar, Sreydy, Kong, Seyha, Kong, Sreytouch, Yorn, Soam, Tes, Sophal, Kep, Seroeung HENG Thy, Leng, Savorn, Neak, Sim, Seng, Pheakna, Pay, Sithan, Suon, Sophanna, Chan, Dyna, Um, Savuth, Sin, Sam, Phan, Sarim, Kum, Sokheng, Khath, Pong, Phem, Seyha, Sok, Chanty, Ny, Van, Leim, Sereyvuth, Pich, Sengkry, Chheang, Nhin, Eang, Vannareth, Sao, Vannak, Sim, Sopheak, Som, Ney, Pong, Sokha, Van, Sreyleap, Seng, Vanna, Yoeurng, Kakada, Toem, Thida, Keo, Vuochny, Sem, Sophal, Veng, Chanthol, Rin, Vanny, Seang, Kiri, Lok, Khemra, Mao, Keovanna, Ouk, Maiya, Min, Suomun, Morm, Rattana, Koy, Sreypov, Chhann, Sreytouch, Set, Audrey, Amboua Schouame, Clifford, Babey, Masama, Eden Ngu, Etienne, Guenou, Sylvie, Kwedi Nolna, Douglas, Mbang Massom, Bernard Fortune, Melingui, Nadia, Nga Elomo, Moïse, Mvetumbo, Angeline, Nkembe, Krystel, Ebo, Albert, Kuate Kuate, Michelline, Choupa, Maggi, Mbede, Valerie, Donkeng, Nelly, Kamgaing, Jean-Voisin, Taguebue, Achille, Touha Yannick, Estelle, Abomo Zang, Rosette, Bakoa, Esperance, Mimbouombela Leger, Sabine, Eleme, Gabrielle, Eteme Marie, Thierry, Elouna Nkoa, Dieudonné, Ndzana, Christophe, Bitti, Olivier, Fotsing, Charlotte, Lani Boko, Mathieu, Mbonga, Ghislain Ulrich, Njakou Sagang, Innocent, Onomo, Charlotte, Essaga Hortense, Daniel Desiré, Mboudi Kouang, Léon, Eloundou, Helene, Kengne, Felix, Mbassi, Juliette, Bidjeme, Hortense, Toua Eteme, Nadege, Essama, Roger, Belinga Balla, Norbert, Tassi, Roline, Nguiko Elsa, Leonard, Mekongo, Fabien, Eyebe Ayissi, Francine Christelle, Biloa Anaba, Philomène, Nsom, Celestin Géraud, Yam Essola, Edwige Léa, Mame Moo, Noé, Makon, Arllette Rita, Nounkep Yanghu, Frank, Ebanga, Antoinette, Assiga Ntsama, Carlyle Sorelle, Kamguia Djuimsop, Diane, Mbabou, Marie, Maguip Abanda, Rosine Berthe, Nguemafouo Doummene, Amos, Mekone, Ngwankfu, Konfor Blessing, Jérome, Mimboe, Virginie, Tiona, Roland, Beleck, Sairou, Zam, Nicole, Adibone, Claude, Biaback Jean, Denis, Bessong, Gilbert, Aminou, Jeremie Pagnol, Bille Bonga, Aubin, Fotso Monkap, Epse NGON Annie, Hitekelek, Vitrice, Sebe, Leo, Makon, Marie, Ennah, Mpie, Paul Boyolo, Diane Viviane, Metchoum, Celin, Nzambe, Arnaud, Dado, Milobert, Mbengang, Marceline, Eyebi, Vanessa, Ngah, Alice, Mballa Batonga, Solange, Ayouba, Pierrette, Ebode, Majino, Mamou, Marguerite, Botomogne Bomba, Salametou, Ngnet, Augustine Florence, Essengue Ngono, Rolland, Odionoloba Charles, Bernice, Bisso, Suzy, Balemaken Ingrid, Marie Louise, Mandoki a Bilong, Gertrude, Ndeng Ayouba, Josue, Ngon, Roger, Aka Bony, Kacou Michel, Bah, Dro, Bakayoko, Rolande, Baki Aimee, Marie-France Larissa, Banga, Olivier, Bouzié, Kan, Brou, Pan, Coulibaly, Serge, Danho, Flavien, Deli, Alphonse, Dion, Bi, Do, Armand, Dohoun, William, Edjeme, Cathérine, Falé, Melissa, Gogoua Saulé, Constant, Kesse, Eric, Komena Auguste, Christian, Kouadio, Arkason, Kouame Abel, Raoul, Moh, Sandrine, Nguessan Marcelle, Bertine, Siloué, Nina, Soua, Cyrille Prisca, Yao Yapi, Timothée, Ouassa, Jacquemin, Kouakou, Eric, Balestre, Aurélie, Beuscart, Aurélie, Charpin, Marc, D'elbee, Hélène, Font, Basant, Joshi, Nicolas, Koskas, Olivier, Marcy, Estelle, Occelli, Joanna, Orne-Gliemann, Julien, Poublan, Elodie, Vernoux, Maryline, Bonnet, Savine, Chauvet, Manon, Lounnas, Guillaume, Breton, Pierre-Yves, Norval, Sheyla, Cassy, Verna, Chambal, Valter, Chiúle, Supinho, Chimbanje, Saniata, Cumbe, Mércia, Matsinhe, Celso, Khosa, Nairo, Mabote, Salvador, Machava, Emelva, Machonisse, Verónica, Macuácua, Denise, Milice, Jorge, Ribeiro, Elcídio, Tivane, Dorlim, Uetela, Yara, Voss de Lima, Américo, Zandamela, Alcina, Zita, Ivan, Manhiça, Benedita, José, Dalila, Rego, Chris, Buck W., Kapoli, Kasembe, Atália, Massangaie, Assa, Sitoe, Ambostique, Argola, Césio, Miambo, Presequila, Nhatsave, Gilda, Sitoe, Charifito, Vesta, Salvador, Dimande, Lázaro, Mazembe, Nilza, Amade, Manuela, Chavela, Nomsa, Macheque, Salomão, Comé, Eulália, Machava, Narciso, Mucavele, Jacinto, Nhabanga, Marlene, Nicolau, Natércia, Simbine, Lina, Uendela, Micaela, Juaio, Abiba, Saíde, Naira, Macie, Fernando, Mondlane, Stélio, Simango, Prince, Beyan, Benjamin M, Flomo, Abubakarr, Jalloh Joseph, Ishmael, Kamara, Monica G, Koroma, Mohamed, Lamin, Lena, Matata, Ross, Mugisha Jacob, Christiana M, Senesie, Sheriff, S.E.S.A.Y., Egerton, Tamba Kamara, Ayeshatu, Mustapha, Lynda, Foray, Sandra, Agondeze, Agnes, Kobusingye, Mastula, Nanfuka, Faith, Namulinda, Eric, Wobudeya, Rinah, Arinaitwe, Rodney, Kaitano, Martin, Kasujja, Juliet, Mwanga-Amumpaire, Evans, Mwesigwa, Naome, Natukunda, Simpson, Nuwamanya, Miria, Nyangoma, Patrick, Orikiriza, Johnbosco, Tumwijukye, Esther, Turyashemererwa, Nyehangane, Dan, Mugisha, Ivan, Winnie, Biryeri, George, Naika, Robert, Ongwara O., Allen, Najjuko, Augustine, Kayiira, Samuel, Yairo, Immaculate, Tumwebaze, Goreth, Nalwoga, Paul, Nsiyaleta, Annet, Agaba, Martin, Mpimbaza M., Norbert, Akampurira, Agatha, Tugumisirize, Evans, Ariyo, Julius, Agaba, Yovita, Natukunda, Nelson, Musazi, Edmund, Musinguzi, Brown, Baluku Julius, Moorine, Sekadde, Stavia, Turyahabwe, Chishala, Chabala, Luis, Cuevas, Christophe, Delacourt, Steve, Graham, Malgorzata, Grzemska, Sabine, Verkuijl, Anneke, Hesseling, Elizabeth, Maleche-Obimbo, Mark, Nicol, Wobudeya, Eric, Nanfuka, Mastula, Ton Nu Nguyet, Minh Huyen, Taguebue, Jean-Voisin, Moh, Raoul, Breton, Guillaume, Khosa, Celso, Borand, Laurence, Mwanga-Amumpaire, Juliet, Mustapha, Ayeshatu, Nolna, Sylvie Kwedi, Komena, Eric, Mugisha, Jacob Ross, Natukunda, Naome, Dim, Bunnet, de Lauzanne, Agathe, Cumbe, Saniata, Balestre, Eric, Poublan, Julien, Lounnas, Manon, Ngu, Eden, Joshi, Basant, Norval, Pierre-Yves, Terquiem, Etienne Leroy, Turyahabwe, Stavia, Foray, Lynda, Sidibé, Souleymane, Manhiça, Ivan, Sekadde, Moorine, Detjen, Anne, Verkuijl, Sabine, Mao, Tan Eang, Orne-Gliemann, Joanna, Bonnet, Maryline, and Marcy, Olivier
Published: 2024
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16. Effect of systematic tuberculosis detection on mortality in young children with severe pneumonia in countries with high incidence of tuberculosis: a stepped-wedge cluster-randomised trial

Author: Olivier Marcy, Eric Wobudeya, Hélène Font, Aurélia Vessière, Chishala Chabala, Celso Khosa, Jean-Voisin Taguebue, Raoul Moh, Juliet Mwanga-Amumpaire, Manon Lounnas, Veronica Mulenga, Sandra Mavale, Josina Chilundo, Dalila Rego, Bwendo Nduna, Perfect Shankalala, Uzima Chirwa, Agathe De Lauzanne, Bunnet Dim, Emeline Tiogouo Ngouana, Madeleine Folquet Amorrissani, Lassina Cisse, Flore Amon Tanoh Dick, Eric A Komena, Sylvie Kwedi Nolna, Gerald Businge, Naome Natukunda, Saniata Cumbe, Prossy Mbekeka, Ang Kim, Chanrithea Kheang, Sokha Pol, Elizabeth Maleche-Obimbo, James A Seddon, Tan Eang Mao, Stephen M Graham, Christophe Delacourt, Laurence Borand, Maryline Bonnet, Angeline Serre, Anne Badrichani, Manoa Razafimanantsoa, Julien Poublan, Clémentine Roucher, Estelle Occelli, Aurélie Beuscart, Aurélie Charpin, Gemma Habiyambere, Salomé Mesnier, Eric Balestre, Bandana Bhatta, Anne-Laure Maillard, Joanna Orne-Gliemann, Emmanuelle Baillet, Nicolas Koskas, Marc D'Elbée, Delphine Gabillard, Minh Huyen, Hélène Espérou, Sandrine Couffin-Cadiergues, Alexis Kuppers, Benjamin Hamze, Laurence BORAND, Agathe de LAUZANNE, Bunnet DIM, Chanthy Keang, Long PRING, Song YIN, Channimol SARITH, Chanvirak PHAN, Sovann NHEUONG, Socheat LY, Sanary KAING, Vouchleang SRENG, Elen LUN, Leakhena SAY, Sophea SUOM, Romyka FERHY, Dina SO, Sorunna BORN, Sophea PAL, Boraneath NANG, Tan Eang MAO, Ang KIM, Viso Srey, Piseth Kan, leakhena Hout, Samnang Ith, Sophany Oum, Sokunvadhana Sau, Kim Heang Ho, Daronic Kith, Nathara Nuch, Chhun Leang Horm, Cheameas Sophon, Bosba Roeungdeth, Chhay MENG, Ravin RITH, Samnang PHY, Chanchetra SOR, Voleak SAO, Sophea KHAT, Bunthoeun MAK, Angkeaborin UY, Sreyny KHAY, Kimsan SOM, rongvirak HACH, Hay SOK, Sotheavy KUON, Synatt HENG, Amara SENG, Sopheak NIM, Reach PAN, Srean KIM, Keo SREY LEAP, Bormey NET, Viccheka NOUN, Daven LAY, Chhaing MANY, Socheata Seng, Vuthy Ly, Saran So, Sovutthik Oun, Sopheap CHEY, Rattany CHHEA, Lydeth BAONG, Vanna THOUNG, Chanrithea KHEANG, Borady BY, Vathanak Nguon, Eksophea MEACH, Sopheak Tek, Sina Ngeav, Tetra Lun, Deth HEM, Nayreang CHUT, Setha SARIK, Hgekkoung NANG, Mengnean MEACH, Sopal SRENG, Dara SAR, Rathana KIN, Phoran ROS, Chenda DORN, Chansy KAK, Srey Leak Sambath, Leakhena Son, Linda Bin, Eangnay Pengong, Samnang Khutsorn, Sorsophea Seang, Virak Soun, Vuthy Vong, Chandara Khoeung, Panha Um, Sokunthea Bou, Sarin Song Pich, Puthy Nim, Sopheak Khat, Nuon Ban Si, Sovannodom Ream, Sim Ing, Phanith Chann, Samrith Ngeth, Marina Sun, Sokea Chhoeung, Soeun Sean, Ratanak Prak, Audrey Amboua Schouame Onambele, Numfor Hycenth, Bernard Melingui, Angeline Nkembe Medounmga, Luciole Hougnang Tatmi, Nathalie Etemgoua, Vanessa Kouesso, Jean Bugin, Celestine Nzedjom, Roger Ngoya, Jules Eyike, Elyse Loudjom, Roger Lonsti, Ladi Dang, Edward Bintar, Chantal Njayong, Cinthia Ngonsoa O, Isabelle Ndzeukap, Pascaline Dzoyem, Clémentine Dzokou, Berthe Dindo, Eric Auguste Komena, Roger Aka Bony, Christian Kouadio, Serge Danho, Melissa Goli, Madeleine Folquet, Max Valère Itchy, Abdel Sidibé, Lancina Cissé, Joseph Ouattara, Mamadou Konaté, Flore Amon-Tanoh Dick, Melissa Cardena, Laurence Adonis-Koffi, Djabia Eugenie, Ferdinand Kouamé, Hervé Menan, André Inwoley, Timothée Ouassa, Marcelle Sandrine Nguessan, Emelva Manhiça, Alcina Zitha, Valter Chiúle, Eva Muxanga, Irene Gune, Yara Lima, Jorge Ribeiro, Felismina Maxanguana, Natália Morais, Julieta Manhiça, Josefina Give, Jafito Atumane, Gelson Lucas, Arsénio Thai, Adélio Chave, Lúcia Guambe, Faiaz Issa, Rosa Carneiro, Neusa Pene, Natércia Florindo, Dália Machel, Cecília Cumbane, Helena Mendes, Mule Kitungwa, Valdo Muianga, Humberto Tamele, Adelino Sulude, Roda Mabota, Herquéria Comandante, Abelardo Massangaie, Gerald Bright Businge, Faith Namulinda, Robert Sserunjogi, Rashidah Nassozi, Charlotte Barungi, Hellen Aanyu, Doreen Muwonge, Eva Kagoya, Serene Aciparu, Sophia Chemutai, Samuel Ntambi, Amir Wasswa, Juliet Nangozi, Abner Tagoola, Sajja Kenneth, John Paul Lubega, Aidah Nassali, Jessica Tagobera, Christine Agwang, Florence Kalembe, Annet Ajambo, Elizabeth Aguti, Samuel Kasibante, Henry Matende, Israel Owen Odongo, Juliet Mwanga Amumpaire, Gertrude Ngabirano, Paul Kakwenza, Simpson Nuwamanya, Miria Nyangoma, Jane Nabbuto, Florence Abok, Rinah Arinaitwe, Diana Birungi, Evans Mwesigwa, Daniel Atwine, Hassan Mbega, Patrick Orikiriza, Ivan Taremwa, Esther Turyashemererwa, Hope Derrick, Dan Nyehangane, Rodney Kaitano, Susan Logoose, Steven Businge, Charles Ntambi, Jerome Mugabi, John Mzee, Julius Besigye, Saul Kanzira, Phionah Turyatemba, Florence Twebaze, Chimuka Hambulo, Vincent Kapotwe, Marjory Ngambi, Kunda Kasakwa, Chifunda Kapula, Susan Zulu, Grace Nawakwi, Teddy Siasulingana, Jessy Chilonga, Maria Chimbini, Mutinta Chilanga, Muleya Inambao, Mwate Mwambazi, Barbra Halende, Wyclef Mumba, Endreen Mankunshe, Maureen Silavwe, Moses Chakopo, and Roy Moono
Subjects: Infectious Diseases
Abstract: Tuberculosis diagnosis might be delayed or missed in children with severe pneumonia because this diagnosis is usually only considered in cases of prolonged symptoms or antibiotic failure. Systematic tuberculosis detection at hospital admission could increase case detection and reduce mortality.We did a stepped-wedge cluster-randomised trial in 16 hospitals from six countries (Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Uganda, and Zambia) with high incidence of tuberculosis. Children younger than 5 years with WHO-defined severe pneumonia received either the standard of care (control group) or standard of care plus Xpert MTB/RIF Ultra (Xpert Ultra; Cepheid, Sunnyvale, CA, USA) on nasopharyngeal aspirate and stool samples (intervention group). Clusters (hospitals) were progressively switched from control to intervention at 5-week intervals, using a computer-generated random sequence, stratified on incidence rate of tuberculosis at country level, and masked to teams until 5 weeks before switch. We assessed the effect of the intervention on primary (12-week all-cause mortality) and secondary (including tuberculosis diagnosis) outcomes, using generalised linear mixed models. The primary analysis was by intention to treat. We described outcomes in children with severe acute malnutrition in a post hoc analysis. This study is registered with ClinicalTrials.gov (NCT03831906) and the Pan African Clinical Trial Registry (PACTR202101615120643).From March 21, 2019, to March 30, 2021, we enrolled 1401 children in the control group and 1169 children in the intervention group. In the intervention group, 1140 (97·5%) children had nasopharyngeal aspirates and 942 (80·6%) had their stool collected; 24 (2·1%) had positive Xpert Ultra. At 12 weeks, 110 (7·9%) children in the control group and 91 (7·8%) children in the intervention group had died (adjusted odds ratio [OR] 0·986, 95% CI 0·597-1·630, p=0·957), and 74 (5·3%) children in the control group and 88 (7·5%) children in the intervention group had tuberculosis diagnosed (adjusted OR 1·238, 95% CI 0·696-2·202, p=0·467). In children with severe acute malnutrition, 57 (23·8%) of 240 children in the control group and 53 (17·8%) of 297 children in the intervention group died, and 36 (15·0%) of 240 children in the control group and 56 (18·9%) of 297 children in the intervention group were diagnosed with tuberculosis. The main adverse events associated with nasopharyngeal aspirates were samples with blood in 312 (27·3%) of 1147 children with nasopharyngeal aspirates attempted, dyspnoea or SpOSystematic molecular tuberculosis detection at hospital admission did not reduce mortality in children with severe pneumonia. High treatment and microbiological confirmation rates support more systematic use of Xpert Ultra in this group, notably in children with severe acute malnutrition.Unitaid and L'Initiative.For the French translation of the abstract see Supplementary Materials section.
Published: 2023

17. Tuberculosis Diagnosis in HIV-Infected Children: Comparison of the 2012 and 2015 Clinical Case Definitions for Classification of Intrathoracic Tuberculosis Disease

Author: Olivier Marcy, Sophie Goyet, Laurence Borand, Philippe Msellati, Vibol Ung, Mathurin Tejiokem, Giang Do Chau, Francis Ateba-Ndongo, Abdoul Salam Ouedraogo, Bunnet Dim, Paul Perez, Julien Asselineau, Guislaine Carcelain, Stéphane Blanche, Christophe Delacourt, and Sylvain Godreuil
Subjects: Infectious Diseases, Vietnam, Burkina Faso, Pediatrics, Perinatology and Child Health, Humans, Tuberculosis, HIV Infections, General Medicine, Child
Abstract: Background There is no gold standard for tuberculosis diagnosis in children. Clinical Case Definitions for Classification of Intrathoracic Tuberculosis in Children were proposed by international experts in 2012 and updated in 2015. We aimed to compare the 2012 and 2015 Clinical Case Definitions in HIV-infected children with suspected tuberculosis. Methods We enrolled HIV-infected children with suspected tuberculosis in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS [Agence Nationale de Recherches sur le SIDA et les hépatites virales] 12229 PAANTHER [Pediatric Asian African Network for Tuberculosis and HIV Research] 01 Study). We classified children using the 2012 and 2015 Case Definitions considering as tuberculosis cases those with confirmed tuberculosis and those with probable and unconfirmed tuberculosis in the 2012 and the 2015 classifications, respectively. We assessed agreement between both classifications. Results Of 438 children enrolled, 197 (45.0%) children were classified as tuberculosis (45 confirmed, 152 probable) using the 2012 Case Definition and 251 (57.3%) were classified as tuberculosis (55 confirmed, 196 unconfirmed) using the 2015 classification. Inter-classification agreement for tuberculosis diagnosis was 364/438, 83.1%, with a kappa statistic of 0.667 (95% confidence interval 0.598-0.736). Of 152 children with probable tuberculosis (2012), 142 (93.4%) were considered as tuberculosis by the 2015 version and 10 (6.6%) as unlikely tuberculosis including 9 with spontaneous clinical improvement. Of 132 possible tuberculosis (2012), 58 (43.9%) were reclassified as tuberculosis (2015). Conclusions Agreement between the 2 versions of the Case Definition was substantial but more children were considered as tuberculosis using the 2015 version. Spontaneous symptom resolution reinforces both confidence in the “unlikely” category as being children without tuberculosis and the importance of the clinician’s treatment decision in the study.
Published: 2021

18. Hepatitis B e Antigen (HBeAg) Rapid Test and Alanine Aminotransferase Level–Based Algorithm to Identify Pregnant Women at Risk of HBV Mother-to-Child Transmission: The ANRS 12345 TA PROHM Study

Author: Bunthoeun Nem, Laurence Borand, Chanlina Vong, Kearena Chhim, Sothy Pech, Olivier Segeral, Say Tiv, Bunnet Dim, Kay Hout, Samsorphea Chhun, Christine Durier, Janin Nouhin, and Sophearot Prak
Subjects: Adult, Microbiology (medical), Hepatitis b e antigen, Hepatitis B virus, HBsAg, Mothers, medicine.disease_cause, Major Articles, 03 medical and health sciences, Hepatitis B, Chronic, 0302 clinical medicine, Pregnancy, medicine, Humans, Hepatitis B e Antigens, 030212 general & internal medicine, Pregnancy Complications, Infectious, Alanine aminotransferase, Child, Online Only Articles, Hepatitis B Surface Antigens, biology, business.industry, public health, mother-to-child transmission, virus diseases, Alanine Transaminase, Hepatitis B, medicine.disease, Infectious Disease Transmission, Vertical, digestive system diseases, AcademicSubjects/MED00290, Infectious Diseases, Alanine transaminase, HBeAg, DNA, Viral, biology.protein, Female, 030211 gastroenterology & hepatology, Pregnant Women, hepatitis B, HBeAg rapid test, business, Algorithm, Algorithms, Western-Pacific area
Abstract: Background The paucity of hepatitis B virus (HBV) DNA measurement in low-/middle-income countries hinders the identification of HBV-infected pregnant women at risk of perinatal transmission. This study evaluates the validity of an algorithm selecting HBeAg-positive women and HBeAg-negative women with alanine aminotransferase (ALT) ≥40 IU/L as a predictor of high HBV DNA level. Methods All women with reactive samples for hepatitis B surface antigen (HBsAg) were assessed with an SD BIOLINE HBeAg rapid test and HBV DNA quantification was performed. Validities of HBeAg and of the algorithm to identify HBV DNA >2 thresholds (5.3 and 7.3 log10 IU/mL) were evaluated. Results For the 515 HBsAg-positive women, median age was 29 years, 92 (17.9%) were HBeAg positive, 47 (9.1%) were HBeAg negative with ALT ≥40 IU/L, and 144 (28.0%) had an HBV DNA >5.3 log10 IU/mL. Sensitivity and specificity of HBeAg were 61.8% and 99.2% for HBV DNA >5.3 log10 IU/mL and 81.3% and 96.7% for HBV DNA >7.3 log10 IU/mL. For the algorithm, sensitivity and specificity were 79.2% and 93.3% for HBV DNA level >5.3 log10 IU/mL and 92.7% and 88.1% for HBV DNA >7.3 log10 IU/mL. The AUCs for the algorithm (0.92 and 0.94 for HBV DNA >5.3 and 7.3, respectively) were significantly greater (P < .001) than the AUCs for HBeAg (0.81 and 0.89 for HBV DNA >5.3 and 7.3, respectively). Conclusions An algorithm using HBeAg and ALT level could be an effective strategy to identify HBV-infected pregnant women at risk of perinatal transmission in countries where HBV DNA quantification is not routinely available., An algorithm selecting Hepatitis B e Antigen (HBeAG)-positive and HBeAg-negative women with ALT ≥40 IU/L could be an effective strategy to identify pregnant women with hepatitis B virus (HBV) eligible for antiviral preventive treatment in countries where HBV DNA quantification is not routinely available.
Published: 2020

19. Prevalence and factors associated with faecal carriage of extended-spectrum β-lactamase-producing Enterobacterales among peripartum women in the community in Cambodia

Author: Agathe, de Lauzanne, Navin, Sreng, Elsa, Foucaud, Touch, Sok, Thida, Chon, Chhaily, Yem, Veasna, Hak, Sothada, Heng, Meng, Soda, Malika, Gouali, Maya, Nadimpalli, Malin, Inghammar, Mamitina Alain Noah, Rabenandrasana, Jean Marc, Collard, Muriel, Vray, Simon Le, Hello, Alexandra, Kerleguer, Patrice, Piola, Elisabeth, Delarocque-Astagneau, Didier, Guillemot, Bich Tram, Huynh, Laurence, Borand, Armya Abdou, Youssouf, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cambodian Communicable Disease Control Department, Institut Pasteur [Paris] (IP), Tufts University [Medford], Lund University [Lund], Institut Pasteur de Madagascar, Institut Pasteur de Dakar, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, Hôpital Raymond Poincaré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), This work was supported by MSDAVENIR and Institut Pasteur., The authors thank Philippe Dussart and Sivuth Ong (Virology Unit, Institut Pasteur du Cambodge) for assistance with PCR and their availability, all BIRDY field monitors for questionnaire administration and sampling management, and Siyin Lach and Long Pring for their involvement in the BIRDY program. We are grateful to all women participating in the BIRDY program. We thank all collaborators of the BIRDY study group., Members of the BIRDY study group: Andrianirina Zafitsara Zo, Marguerite Diatta, Jean Baptiste Diouf, Fatoumata Diene Sarr, Joseph Faye, Sophie Goyet, Perlinot Herindrainy, Elsa Kermorvant-Duchemin, Siyin Lach, Veronique Ngo, Michael Padget, Feno Manitra Jacob Rakotoarimanana, Bodonirina Tanjona Raheliarivao, Frédérique Randrianirina, Abdoulaye Seck, Arnaud Tarantola and Armya Abdou Youssouf., and Bich-Tram, Huynh
Subjects: Pharmacology, Microbiology (medical), Infant, Newborn, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, beta-Lactamases, Anti-Bacterial Agents, Feces, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Escherichia coli, Peripartum Period, Prevalence, Humans, Pharmacology (medical), [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cambodia, Escherichia coli Infections
Abstract: Background In Southeast-Asia, where many conditions associated with dissemination of ESBL-producing Enterobacterales (ESBL-E) in the community are met, data from the community are scarce but show high ESBL-E carriage prevalence. Maternal ESBL-E colonization is considered a risk factor for neonatal colonization, which is the first step towards developing neonatal sepsis. Despite this, ESBL-E carriage prevalence and its risk factors during pregnancy or postpartum remain undefined in Southeast-Asia. Objectives To estimate the prevalence of ESBL-E faecal colonization among peripartum women in the community of an urban and a rural area in Cambodia, to investigate ESBL-E genomic characteristics and to identify associated risk factors. Methods Epidemiological data and faecal samples from 423 peripartum women were collected in an urban and rural areas in Cambodia (2015–16). Bacterial cultures, antibiotic susceptibility tests and ESBL gene sequencing were performed. Risk factor analysis was conducted using logistic regression. Results The prevalence of ESBL-E faecal carriage was 79.2% (95% CI 75.0%–82.8%) among which Escherichia coli (n = 315/335, 94.0%) were most frequent. All isolates were multidrug resistant. Among 318 ESBL-E, the genes most frequently detected were blaCTX-M-15 (41.5%), blaCTX-M-55 (24.8%), and blaCTX-M-27 (15.1%). Low income, undernutrition, multiparity, regular consumption of pork, dried meat, and raw vegetables, were associated with ESBL-E faecal carriage. Conclusions The high prevalence of ESBL-E carriage observed among peripartum women in Southeast-Asia and the identified associated factors underline the urgent need for public health measures to address antimicrobial resistance, including a ‘One Health’ approach.
Published: 2022

20. CTX-M-55-type ESBL-producingSalmonella entericaare emerging among retail meats in Phnom Penh, Cambodia

Author: Laurence Watier, Bouya Ndao, Didier Guillemot, Vuthy Yith, Thida Chon, Patrice Piola, Maud Seguy, Balla Sy, Perlinot Herindrainy, Muriel Vray, Alexandra Kerleguer, Marguerite Diatta, Jean Baptiste Diouf, Zafitsara Zo Andrianirina, Siyin Lach, Laetitia Fabre, Malika Gouali, Benoit Garin, Nita Sem, Bich-Tram Huynh, Raymond Bercion, Bodonirina Tanjona Raheliarivao, Abdou Armya Youssouf, Vincent Richard, Frédérique Randrianirina, Navin Sreng, Elisabeth Delarocque-Astagneau, Agathe de Lauzanne, Feno Manitra Jacob Rakotoarimanana, Veronique Ngo, Laurence Borand, Sophie Goyet, Joseph Faye, Michael Padget, Sok Touch, Jean-Marc Collard, Pape Samba Dieye, Arnaud Tarantola, Abibatou Ndiaye, Abdoulaye Seck, Amy Gassama Sow, Maya Nadimpalli, Simon Le Hello, Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bactéries pathogènes entériques (BPE), Institut Pasteur [Paris] (IP), Laboratory of Environment and Food Safety [Phnom Penh, Cambodia], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Hôpital Raymond Poincaré [AP-HP], This work was supported by the Dennis and Mireille Gillings Foundation, Pasteur Foundation US, MSD AVENIR, Monaco Department of International Cooperation and Institut Pasteur., Members of the BIRDY study group : Bodonirina Tanjona Raheliarivao, Frédérique Randrianirina, Perlinot Herindrainy, Zafitsara Zo Andrianirina, Feno Manitra Jacob Rakotoarimanana, Benoit Garin, Jean-Marc Collard, Agathe de Lauzanne, Laurence Borand, Patrice Piola, Alexandra Kerléguer, Thida Chon, Sok Touch, Arnaud Tarantola, Sophie Goyet, Siyin Lach, Veronique Ngo, Muriel Vray, Marguerite Diatta, Joseph Faye, Abibatou Ndiaye, Vincent Richard, Abdoulaye Seck, Raymond Bercion, Amy Gassama Sow, Jean Baptiste Diouf, Pape Samba Dieye, Balla Sy, Bouya Ndao, Didier Guillemot, Bich-tram Huynh, Maud Seguy, Laurence Watier, Abdou Armya Youssouf and Michael Padget., RANDRIAMANANTSOA, Volatiana Manohisoa, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Microbiology (medical), Serotype, Salmonella, Veterinary medicine, Meat, Cefotaxime, Gene Transfer, Horizontal, medicine.drug_class, 030106 microbiology, Antibiotics, Biology, medicine.disease_cause, Poultry, beta-Lactamases, 03 medical and health sciences, 0302 clinical medicine, Plasmid, Bacterial Proteins, Drug Resistance, Multiple, Bacterial, Prevalence, medicine, Animals, Pharmacology (medical), 030212 general & internal medicine, 2. Zero hunger, Pharmacology, Salmonella Infections, Animal, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, business.industry, Fishes, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Salmonella enterica, biology.organism_classification, Food safety, Anti-Bacterial Agents, 3. Good health, Phnom penh, Infectious Diseases, Food Microbiology, Cambodia, business, Chickens, Genome, Bacterial, Plasmids, medicine.drug
Abstract: Members of the BIRDY study group : Bodonirina Tanjona Raheliarivao, Frédérique Randrianirina, Perlinot Herindrainy, Zafitsara Zo Andrianirina, Feno Manitra Jacob Rakotoarimanana, Benoit Garin, Jean-Marc Collard, Agathe de Lauzanne, Laurence Borand, Patrice Piola, Alexandra Kerléguer, Thida Chon, Sok Touch, Arnaud Tarantola, Sophie Goyet, Siyin Lach, Veronique Ngo, Muriel Vray, Marguerite Diatta, Joseph Faye, Abibatou Ndiaye, Vincent Richard, Abdoulaye Seck, Raymond Bercion, Amy Gassama Sow, Jean Baptiste Diouf, Pape Samba Dieye, Balla Sy, Bouya Ndao, Didier Guillemot, Bich-tram Huynh, Maud Seguy, Laurence Watier, Abdou Armya Youssouf and Michael Padget.; International audience; BACKGROUND:Salmonella enterica is a leading cause of human gastroenteritis. S. enterica strains that produce ESBLs (ESBL-Salm) remain rare in Europe and North America, but less is known about their prevalence among animal-derived foods in countries with weaker food safety practices and unregulated veterinary antibiotic use.OBJECTIVES:To examine the prevalence and characteristics of ESBL-Salm from retail meats in Phnom Penh, Cambodia.METHODS:We tested fish, pork and chicken from two markets for ESBL- and carbapenemase-producing Salmonella from September-December 2016, using cefotaxime- and ertapenem-supplemented media, respectively. ESBL-Salm were sequenced and their genomes characterized. We performed plasmid conjugation experiments to assess the co-transferability of ESBL-encoding genes and MDR phenotypes.RESULTS:Twenty-six of 150 fish and meat samples (17%) were positive for ESBL-Salm, including 10/60 fish (17%), 15/60 pork (25%) and 1/30 chicken (3%). Carbapenemase-producing Salmonella strains were not detected. Pork-origin ESBL-Salm were primarily serotypes Rissen (10/15) or a monophasic variant of Typhimurium 4,5,12:i:- (3/15), whereas Saintpaul (3/10) and Newport (4/10) were more common among fish. Most ESBL enzymes were encoded by blaCTX-M-55 genes (24/26) harboured on conjugative IncA/C2 (n = 14) or IncHI2 (n = 10) plasmids. Resistance to up to six additional drug classes was co-transferred by each plasmid type. ESBL-Salm were resistant to almost every antibiotic recommended for severe salmonellosis treatment.CONCLUSIONS:CTX-M-55-type S. enterica are highly prevalent among pork and fish from Phnom Penh markets and their spread appears to be mediated by MDR IncA/C2 and IncHI2 plasmids. Food safety must be improved and veterinary antibiotic use should be regulated to protect public health.
Published: 2018

21. Excess risk of subsequent infection in hospitalized children from a community cohort study in Cambodia and Madagascar

Author: Lison Rambliere, Elsa Kermorvant-Duchemin, Agathe de Lauzanne, Jean-Marc Collard, Perlinot Herindrainy, Muriel Vray, Benoit Garin, Andrianirina Zafitsara Zo, Fanjalalaina Rasoanaivo, Jacob Rakotoarimanana Feno Manitra, Tanjona Bodonirina Raheliarivao, Jean-Baptiste Niokhhor Diouf, Véronique Ngo, Siyin Lach, Pring Long, Laurence Borand, Touch Sok, Armiya Youssouf Abdou, Michael Padget, Yoann Madec, Didier Guillemot, Elisabeth Delarocque-Astagneau, Bich-Tram Huynh, Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Madagascar, Institut Pasteur de Dakar, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre Hospitalier de Soavinandriana (CENHOSOA), Centre Hospitalier Roi Baudouin, Ministry of Health [Hanoi], Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), This work was supported by internal resources from University Paris-Sud. The research project BIRDY was implemented with the financial support of the Monegasque co-operation for development, the Total Foundation and MSDAVENIR., and We are grateful to the BIRDY study group (Supplementary Text S2, available as Supplementary data at IJE online), all mothers and their newborns, physicians, laboratory staff, field investigators, community workers and collaborators for their participation in this project and David R.M. Smith for his proofreading in English.
Subjects: Epidemiology, global health, Infant, General Medicine, cohort, infection, diarrhoea, post-hospital syndrome, sepsis, Cohort Studies, Hospitalization, Madagascar, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, low- and middle-income countries, lower-respiratory infection, Prospective Studies, hospital, Cambodia, Child, Children, Child, Hospitalized, Respiratory Tract Infections, care pathway
Abstract: Background Children in low- and middle-income countries are particularly vulnerable in the months following an initial health event (IHE), with increased risk of mortality caused mostly by infectious diseases. Due to exposure to a wide range of environmental stressors, hospitalization in itself might increase child vulnerability at discharge. The goal of this study was to disentangle the role of hospitalization on the risk of subsequent infection. Methods Data from a prospective, longitudinal, international, multicenter mother-and-child cohort were analysed. The main outcome assessed was the risk of subsequent infection within 3 months of initial care at hospital or primary healthcare facilities. First, risk factors for being hospitalized for the IHE (Step 1) and for having a subsequent infection (Step 2) were identified. Then, inpatients were matched with outpatients using propensity scores, considering the risk factors identified in Step 1. Finally, adjusted on the risk factors identified in Step 2, Cox regression models were performed on the matched data set to estimate the effect of hospitalization at the IHE on the risk of subsequent infection. Results Among the 1312 children presenting an IHE, 210 (16%) had a subsequent infection, mainly lower-respiratory infections. Although hospitalization did not increase the risk of subsequent diarrhoea or unspecified sepsis, inpatients were 1.7 (95% Confidence Intervals [1.0–2.8]) times more likely to develop a subsequent lower-respiratory infection than comparable outpatients. Conclusion For the first time, our findings suggest that hospitalization might increase the risk of subsequent lower-respiratory infection adjusted on severity and symptoms at IHE. This highlights the need for robust longitudinal follow-up of at-risk children and the importance of investigating underlying mechanisms driving vulnerability to infection.
Published: 2021

22. Diagnosis and management of latent tuberculosis infection in Asia: Review of current status and challenges

Author: Yi-Wen Huang, Nicholas I. Paton, Nastiti Kaswandani, Nandini Sharma, Charoen Chuchottaworn, Grace Lui, Laurence Borand, Asif Mujtaba Mahmud, Jubert Benedicto, Mohd Nor Norazmi, Tan Eang Mao, Mar Mar Kyi, and Hoi Le Van
Subjects: 0301 basic medicine, Microbiology (medical), Prioritization, medicine.medical_specialty, Asia, Tuberculosis, 030106 microbiology, Antitubercular Agents, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Risk groups, Latent Tuberculosis, Political science, medicine, Humans, lcsh:RC109-216, 030212 general & internal medicine, Latent tuberculosis, General Medicine, bacterial infections and mycoses, medicine.disease, Infectious Diseases, Who guidelines, Family medicine, Professional association
Abstract: Asia has the highest burden of tuberculosis (TB) and latent TB infection (LTBI) in the world. Optimizing the diagnosis and treatment of LTBI is one of the key strategies for achieving the WHO ‘End TB’ targets. We report the discussions from the Asia Latent TubERculosis (ALTER) expert panel meeting held in 2018 in Singapore. In this meeting, a group of 13 TB experts from Bangladesh, Cambodia, Hong Kong, India, Indonesia, Malaysia, Myanmar, the Philippines, Singapore, Taiwan, Thailand and Vietnam convened to review the literature, discuss the barriers and propose strategies to improve the management of LTBI in Asia. Strategies for the optimization of risk group prioritization, diagnosis, treatment, and research of LTBI are reported. The perspectives presented herein, may help national programs and professional societies of the respective countries enhance the adoption of the WHO guidelines, scale-up the implementation of national guidelines based on the regional needs, and provide optimal guidance to clinicians for the programmatic management of LTBI. Keywords: Latent tuberculosis infection, Asia, Awareness, Optimization
Published: 2019

23. Usefulness of a serial algorithm of HBsAg and HBeAg rapid diagnosis tests to detect pregnant women at risk of HBV mother-to-child transmission in Cambodia, the ANRS 12328 pilot study

Author: Laurence Borand, Wootichai Khamduang, Samsorphea Chhun, Nicole Ngo-Giang-Huong, Janin Nouhin, Patrice Piola, Kenrena Chim, Anne-Marie Roque-Afonso, Dieynaba S N'Diaye, François Rouet, Olivier Segeral, and Sophearot Prak
Subjects: Hepatitis B virus, Perinatal transmission, HBsAg, Mother to child transmission, Pilot Projects, Hepatitis b surface antigen, medicine.disease_cause, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Virology, parasitic diseases, medicine, Humans, Hepatitis B e Antigens, Viremia, 030212 general & internal medicine, Pregnancy Complications, Infectious, Hepatitis B Surface Antigens, Plasma samples, Diagnostic Tests, Routine, business.industry, virus diseases, Elisa assay, Hepatitis B, Infectious Disease Transmission, Vertical, digestive system diseases, Infectious Diseases, HBeAg, DNA, Viral, Female, 030211 gastroenterology & hepatology, Pregnant Women, Cambodia, business, Algorithm, Algorithms
Abstract: Background In Cambodia, access to hepatitis B surface antigen (HBsAg) screening is low for pregnant women and Hepatitis B Virus (HBV) DNA quantification is poorly accessible. Objectives To evaluate the performance of a serial algorithm using two HBV rapid diagnostic tests (RDTs), in which samples positive for HBsAg were further tested for HBeAg as a surrogate marker for HBV DNA quantification. Study design In 2015, we prospectively collected plasma samples from 250 pregnant women consulting for antenatal care in one hospital in Phnom Penh including 128 with a known positive HBsAg status. All specimens were tested with the SD BIOLINE HBsAg RDT and HBsAg ELISA assay. In ELISA-positive samples, HBeAg status was determined using the SD BIOLINE HBeAg RDT and HBV DNA quantification was assessed. Results Sensitivity and specificity of HBsAg RDT were 99.2% (97.7–99.9) and 100% (97.0–100), respectively. Among the 128 ELISA-positive samples, 29 (23%) tested HBeAg positive and 34 (26.5%) had HBV DNA > 5.3 Log10 IU/mL. Sensitivity and specificity of HBeAg RDT in identifying viremic samples were 76.5% (62.2.0–90.7) and 96.8% (93.3–100) for HBV DNA > 5.3 Log10 IU/mL and 89.3% (77.8–100) and 96.0% (92.2–99.8) for HBV DNA > 7.3 Log10IU/mL. Among the 99 negative HBeAg RDT women, 8 had HBV DNA > 5.3 Log10 IU/mL and 7 of them harbored BCP/PC HBV mutants. Conclusions A combination of HBsAg and HBeAg RDTs could be a low-cost strategy to identify HBV-infected pregnant women at risk of perinatal transmission in a country were HBV DNA quantification is not routinely available.
Published: 2018

24. Impact of systematic early tuberculosis detection using Xpert MTB/RIF Ultra in children with severe pneumonia in high tuberculosis burden countries (TB-Speed pneumonia): a stepped wedge cluster randomized trial

Author: Mao Tan Eang, Laurence Borand, Maryline Bonnet, Sylvain Godreuil, Olivier Marcy, Raoul Moh, Jean-Voisin Taguebue, Sandra Mavale, Juliet Mwanga-Amumpere, Manon Lounnas, James A Seddon, Veronica Mulenga, Celso Khosa, Eric Wobudeya, Hélène Font, Aurélia Vessière, Chishala Chabala, Laurence Adonis-Koffi, Delphine Gabillard, Christophe Delacourt, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Zambia [Lusaka] (UNZA), Maputo Central Hospital, Ministry of Health [Mozambique], Centre Hospitalier Universitaire [Treichville] (CHU), Epicentre Ouganda [Mbarara] [Médecins Sans Frontières], Epicentre [Paris] [Médecins Sans Frontières], National Center for Tuberculosis and Leprosy Control [Phnom Penh, Cambodia] (CENAT), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Stellenbosch University, Imperial College London, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Bugema University [Kampala], Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), and Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Pediatrics, Nasopharyngeal aspirate, Aftercare, 030204 cardiovascular system & hematology, law.invention, Study Protocol, 0302 clinical medicine, Randomized controlled trial, law, Clinical endpoint, Uganda, 030212 general & internal medicine, Cluster randomised controlled trial, Cameroon, Child, Children, Mozambique, Cause of death, lcsh:RJ1-570, Diagnostic Trial, Patient Discharge, 3. Good health, Stool, Child, Preschool, Cambodia, Life Sciences & Biomedicine, medicine.medical_specialty, Tuberculosis, Zambia, Disease cluster, Xpert MTB, Sensitivity and Specificity, 03 medical and health sciences, RIF ultra, medicine, Humans, Xpert, Science & Technology, business.industry, lcsh:Pediatrics, Mycobacterium tuberculosis, Pneumonia, medicine.disease, Xpert MTB/RIF ultra, Pediatrics, Perinatology and Child Health, MTB, 1114 Paediatrics and Reproductive Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Background In high tuberculosis (TB) burden settings, there is growing evidence that TB is common in children with pneumonia, the leading cause of death in children under 5 years worldwide. The current WHO standard of care (SOC) for young children with pneumonia considers a diagnosis of TB only if the child has a history of prolonged symptoms or fails to respond to antibiotic treatments. As a result, many children with TB-associated severe pneumonia are currently missed or diagnosed too late. We therefore propose a diagnostic trial to assess the impact on mortality of adding the systematic early detection of TB using Xpert MTB/RIF Ultra (Ultra) performed on nasopharyngeal aspirates (NPA) and stool samples to the WHO SOC for children with severe pneumonia, followed by immediate initiation of anti-TB treatment in children testing positive on any of the samples. Methods TB-Speed Pneumonia is a pragmatic stepped-wedge cluster randomized controlled trial conducted in six countries with high TB incidence rate (Côte d’Ivoire, Cameroon, Uganda, Mozambique, Zambia and Cambodia). We will enrol 3780 children under 5 years presenting with WHO-defined severe pneumonia across 15 hospitals over 18 months. All hospitals will start managing children using the WHO SOC for severe pneumonia; one hospital will be randomly selected to switch to the intervention every 5 weeks. The intervention consists of the WHO SOC plus rapid TB detection on the day of admission using Ultra performed on 1 nasopharyngeal aspirate and 1 stool sample. All children will be followed for 3 months, with systematic trial visits at day 3, discharge, 2 weeks post-discharge, and week 12. The primary endpoint is all-cause mortality 12 weeks after inclusion. Qualitative and health economic evaluations are embedded in the trial. Discussion In addition to testing the main hypothesis that molecular detection and early treatment will reduce TB mortality in children, the strength of such pragmatic research is that it provides some evidence regarding the feasibility of the intervention as part of routine care. Should this intervention be successful, safe and well tolerated, it could be systematically implemented at district hospital level where children with severe pneumonia are referred. Trial registration ClinicalTrials.gov, NCT03831906. Registered 6 February 2019.
Published: 2021

25. Leakiness at the human-animal interface in Southeast Asia and implications for the spread of antibiotic resistance

Author: Søren Overballe-Petersen, Sem N, Bich-Tram Huynh, Yith, Lance B. Price, Thong Phe, Victor O. Leshyk, Roberto Viau, Timothy J. Johnson, Amy J. Pickering, Gravey F, Sylvain Brisse, Jan Jacobs, Bruce A. Hungate, de Lauzanne A, Malika Gouali, Maliha Aziz, Marc Stegger, Laurence Borand, Maya Nadimpalli, Simon Le Hello, Cindy M. Liu, and Passet
Subjects: Human animal, Antibiotic resistance, Sanitation, Resistance (ecology), Hygiene, Environmental health, media_common.quotation_subject, Biosecurity, Antibiotic use, Biology, Southeast asia, media_common
Abstract: International efforts to curb antimicrobial resistance have focused on drug development and limiting unnecessary use. However, in areas where water, sanitation, and hygiene infrastructure is lacking, and where biosecurity in food-animal production is poor, pathogen-flow between humans and animals could exacerbate the emergence and spread of resistant pathogens. Here, we compared mobile resistance elements among Escherichia coli recovered from humans and meat in Cambodia, a country with substantial connectivity between humans and animals, unregulated antibiotic use, and poor environmental controls. We identified multiple resistance-encoding plasmids and a novel, blaCTX-M and qnrS1-encoding transposon that were widely dispersed in both humans and animals, a phenomenon rarely observed in high-income settings. Our findings indicate that plugging leaks at human-animal interfaces should be a critical part of addressing antimicrobial resistance in low and middle-income countries.
Published: 2021

26. Excess Risk of Subsequent Infection in Hospitalized Children: Evidence from a Community Cohort Study in Cambodia and Madagascar

Author: Lison Rambliere, Elsa Kermorvant-Duchemin, Agathe De Lauzanne, Jean-Marc Collard, Perlinot Herindrainy, Muriel Vray, Benoit Garin, Andrianirina Zafitsara Zo, Fanjalalaina Rasoanaivo, Feno Manitra Jacob Rakotoarimanana, Tanjona Bodonirina Raheliarivao, Jean Baptiste Niokhhor Diouf, Véronique Ngo, Siyin Lach, Pring Long, Laurence Borand, Touch Sok, Armiya Youssouf Abdou, Michael Padget, Yoann Madec, Didier Guillemot, Elisabeth Delarocque-Astagneau, and Bich-Tram Huynh
Published: 2021

27. Systematic or Test-Guided Treatment for Tuberculosis in HIV-Infected Adults

Author: François-Xavier, Blanc, Anani D, Badje, Maryline, Bonnet, Delphine, Gabillard, Eugène, Messou, Conrad, Muzoora, Sovannarith, Samreth, Bang D, Nguyen, Laurence, Borand, Anaïs, Domergue, Delphine, Rapoud, Naome, Natukunda, Sopheak, Thai, Sylvain, Juchet, Serge P, Eholié, Stephen D, Lawn, Serge K, Domoua, Xavier, Anglaret, Didier, Laureillard, Thi Hai Ly, Tran, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Department of Medicine, Harvard Medical School [Boston] (HMS), emlyon business school, Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Réseau International des Instituts Pasteur (RIIP), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Programme PAC-CI, Centre Hospitalier Universitaire [Treichville] (CHU), The Desmond Tutu HIV Centre Institute of Infectious Disease and Molecular Medicine, University of Cape Town, ANRS France Recherche Nord & sud Sida-hiv hépatites, and Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)
Subjects: Adult, Male, medicine.medical_specialty, Tuberculosis, [SDV]Life Sciences [q-bio], Antitubercular Agents, HIV Infections, 030204 cardiovascular system & hematology, law.invention, IDLIC, Immunocompromised Host, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Tuberculosis diagnosis, law, Internal medicine, medicine, Humans, 030212 general & internal medicine, Adverse effect, Ethambutol, ComputingMilieux_MISCELLANEOUS, Bacterial disease, AIDS-Related Opportunistic Infections, business.industry, Hazard ratio, HIV, Bacterial Infections, General Medicine, Viral Load, Pyrazinamide, medicine.disease, CD4 Lymphocyte Count, 3. Good health, Anti-Retroviral Agents, Female, business, medicine.drug
Abstract: Background In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death. Methods We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization. Results A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment. Conclusions Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events. (Funded by the Agence Nationale de Recherches sur le Sida et les Hepatites Virales; STATIS ANRS 12290 ClinicalTrials.gov number, NCT02057796.).
Published: 2020

28. Klebsiella pneumoniae carriage in low-income countries: antimicrobial resistance, genomic diversity and risk factors

Author: Jean-Marc Collard, Perlinot Herindrainy, Raymond Bercion, Didier Guillemot, Maria Pardos de la Gandara, Andriniaina Rakotondrasoa, Benoit Garin, Elisabeth Delarocque-Astagneau, Agathe de Lauzanne, Melanie Hennart, Sylvain Brisse, Carla Rodrigues, Virginie Passet, Thierno Abdoulaye Diallo, Muriel Vray, Bich-Tram Huynh, Alexandra Kerleguer, Laurence Borand, Abdoulaye Seck, Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris], Unité de Bactériologie Expérimentale [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur du Cambodge, Institut Pasteur de Bangui, Centre National de Référence - National Reference Center Escherichia coli, Shigella et Salmonella (CNR-ESS), This work was supported by the Institut Pasteur programme Action Concertee Inter-Pasteurienne (Grant A-14-2014) and by the French government’s Investissement d’Avenir program Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant ANR-10-LABX-62-IBEID). Support to the BIRDY project was provided by the Total Foundation, MSDAVENIR and the Monaco Department of International Cooperation. CR was supported financially by the MedVetKlebs project, a component of European Joint Programme One Health EJP, which has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 773830. The funders had no role in study design, data collection and analysis, interpretation, or writing of the manuscript., We thank all collaborators of the BIRDY program: Rasoanaivo Fanjalalaina Vololonirina, Andrianonimiadana Lova Maminirina, Rabearitiana Lydos, Rasoloson Dimitri, Randrianirina Frédérique, Ratsima Hariniaina Elisoa, Volahasina Antsa Tanjona, Volahasina Antso Fenitra, Randriamamonjiarison Aina Nirina, Andrianirina Zafitsara Zo, Andriatahina Todisoa, Vincent Richard, Awa Ndir, Amy Gassama Sow, Balla Sy, Marguerite Diatta, Pape Samba Dieye, Jean Baptiste Diouf, Joseph Faye, Abibatou Ndiaye, Bouya Ndao, Thida Chon, Veronique Ngo, Arnaud Tarantola, Sok Touch, Patrice Piola, Sophie Goyet, Siyin Lach, Elsa Kermorvant-Duchemin, Michael Padget, Laurence Watier, and Abdou Armya Youssouf. We thank all physicians, laboratory staff, field interviewers, and community workers involved in the project. We thank Leonardo Panunzi for assistance with genomic analyses of resistance genes, and the 'Plateforme de Microbiologie Mutualisée' of Institut Pasteur for genomic sequencing. We are grateful to all women participating in the BIRDY program., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health EJP)(2018), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health)(2018), Moulherat, Isabelle, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Klebsiella pneumoniae: from ecology to source attribution and transmission control - MedVetKlebs (a component of European Joint Programme One Health) - - H2020-SFS-2017-12018-01-01 - 2019-12-31 - 773830 - VALID
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, antibiotic resistance, Klebsiella pneumoniae, media_common.quotation_subject, Developing country, RC799-869, Biology, Microbiology, genomic diversity, 03 medical and health sciences, 0302 clinical medicine, Antibiotic resistance, low-income countries, medicine, media_common, carriage, 2. Zero hunger, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Public health, Gastroenterology, Diseases of the digestive system. Gastroenterology, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Multiple drug resistance, 030104 developmental biology, Infectious Diseases, Carriage, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Research Paper/Report, community, 030211 gastroenterology & hepatology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Diversity (politics), Research Article
Abstract: The genomic sequencing data were deposited in the NCBI/ENA/DDBJ databases and are accessible via the BioProject PRJEB29143; International audience; Klebsiella pneumoniae (hereafter, Kp) is a major public health threat responsible for high levels of multidrug resistant (MDR) human infections. Besides, Kp also causes severe infections in the community, especially in Asia and Africa. Although most Kp infections are caused by endogenous intestinal carriage, little is known about the prevalence and microbiological characteristics of Kp in asymptomatic human carriage, and attached risk factors including environmental sources exposure. Here, 911 pregnant women from communities in Madagascar, Cambodia, and Senegal were screened for gut colonization by Kp. Characteristics of Kp strains (antimicrobial susceptibility, genomic diversity, virulence, and resistance genes) were defined, and associated risk factors were investigated.Kp carriage rate was 55.9%, and Kp populations were highly heterogeneous (6 phylogroups, 325 sequence types, Simpson index 99.6%). One third of Kp isolates had acquired antimicrobial resistance genes. MDR-Kp (11.7% to 39.7%) and extended spectrum beta-lactamase (ESBL)-producing Kp (0.7% to 14.7%) varied among countries. Isolates with virulence genes were detected (14.5%). Environmental exposure factors including food, animal contacts, or hospitalization of household members were associated with carriage of Kp, antimicrobial resistance and hypervirulence. However, risk factors were country-specific and Kp subpopulation-specific.This large-scale multicenter study uncovers the huge diversity of Kp in human gut carriage, demonstrates that antimicrobial resistance is widespread in communities of three low-income countries, and underlines the challenges posed by Kp colonization to the control of antimicrobial
Published: 2020

29. A 1-week intradermal dose-sparing regimen for rabies post-exposure prophylaxis (RESIST-2): an observational cohort study

Author: Yiksing Peng, Arnaud Tarantola, Chun Navy Taing, Chandara Phoeun, Sotheary In, Tineke Cantaert, Chanthy Hing, Rithy Choeung, Sivlin Ung, Channa Mey, Lauriane Kergoat, Manil Saman, Philippe Dussart, Sowath Ly, Laurence Borand, Chanthy Leng, Hervé Bourhy, Sivuth Ong, Immunologie [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Centre collaborateur de l'OMS - Rage / World Health Organization Collaboration Centres - Rabies (CC-OMS / WHO-CC), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Unité de Virologie / Virology Unit [Phnom Penh], The study was done with support and funding from Institut Pasteur (for the serological analysis), Direction Internationale of Institut Pasteur (for the Rabies Elimination Support through Integrative Science and Therapy programme through an Action Concertées InterPasteuriennes grant), and Institut Pasteur du Cambodge., We thank all patients and participants for their involvement in the study. We thank Erik Karlsson for his help in determining the nutrition status of children., and Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)
Subjects: 0301 basic medicine, Male, Pediatrics, medicine.medical_treatment, MESH: Rabies virus / immunology, medicine.disease_cause, Antibodies, Viral, Cohort Studies, MESH: Dogs, MESH: Rabies / prevention & control, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, MESH: Immunization Schedule, MESH: Post-Exposure Prophylaxis* / methods, MESH: Animals, 030212 general & internal medicine, Young adult, Child, MESH: Rabies Vaccines / administration & dosage, MESH: Cohort Studies, 2. Zero hunger, biology, Vaccination, MESH: Neutralization Tests, Age Factors, 3. Good health, Infectious Diseases, MESH: Young Adult, Female, Antibody, Post-Exposure Prophylaxis, Cohort study, Adult, medicine.medical_specialty, Adolescent, Injections, Intradermal, Rabies, MESH: Antibodies, Viral / immunology, 03 medical and health sciences, Young Adult, Dogs, Neutralization Tests, medicine, Animals, Humans, Post-exposure prophylaxis, MESH: Antibodies, Neutralizing / immunology, Immunization Schedule, MESH: Adolescent, MESH: Age Factors, MESH: Injections, Intradermal, MESH: Humans, business.industry, Rabies virus, MESH: Adult, MESH: Vaccination, medicine.disease, Antibodies, Neutralizing, MESH: Male, Regimen, 030104 developmental biology, Rabies Vaccines, biology.protein, business, MESH: Female
Abstract: Comment in : Improving human rabies post-exposure prophylaxis. / Blumberg L, Rupprecht CE. Lancet Infect Dis. 2019 Dec;19(12):1273-1274. doi: 10.1016/S1473-3099(19)30525-0. Epub 2019 Sep 27. PMID: 31570310; International audience; Background: The international health authorities are backing an effort to eliminate canine-mediated rabies in humans by 2030. This effort will require improving access to adequate and timely rabies post-exposure prophylaxis as compliance is low with WHO-recommended regimens (given in four to five visits over 1 month). Access could be substantially improved by an abridged regimen to reduce doses, direct and indirect costs, and improve vaccine equity by better sharing of available vaccine. We aimed to compare rabies virus neutralising antibody titres before and after the fourth visit to determine whether that session was needed or the current regimen could be abridged.Methods: In this observational cohort study, we measured rabies virus neutralising antibody titres using rapid fluorescent focus inhibition tests in 116 people bitten by dogs with laboratory-confirmed rabies and 20 control individuals. Percentages of circulating plasmablasts were determined by flow cytometry. All individuals had been referred to the rabies prevention clinic at Institut Pasteur in Cambodia and received two intradermal injections of post-exposure prophylaxis on days 0, 3, 7, and 28 (Thai Red Cross regimen) with or without equine rabies immunoglobulin, as per 2010 WHO recommendations.Findings: All individuals had rabies virus neutralising antibody titres considered protective (≥0·5 IU/mL) and plasmablast activation on day 28 before the last injection. The median rabies virus neutralising antibody concentration in the group of individuals bitten by rabies virus-positive dogs was 1·08 IU/mL (IQR 0·37-3·09) on day 7, 26·86 (22·68-49·50) on day 28, and 26·74 (11·78-49·06) on day 42. No significant differences were observed in titres between days 28 and 42, after titres reached a plateau. These titres were reached notwithstanding equine rabies immunoglobulin use, age, sex, nutrition status as indicated by upper-arm circumference in children or BMI in adults, or dog infection status. Titres or plasmablast percentages did not increase between the day of the last injection and 2 weeks later. All patients were alive 1 year after post-exposure prophylaxis.Interpretation: The fourth vaccine session on day 28 provides no additional benefit. Rabies post-exposure prophylaxis can be abridged to a two-dose, three-session, 1 week regimen to improve post-exposure prophylaxis coverage and equity at no risk to patients.
Published: 2019

30. In-field Evaluation of SD Bioline HBsAg Whole Blood Rapid Test in Pregnant Women in Cambodia: the ANRS 12345 TA PROHM Study

Author: Olivier Segeral, Song Yin, Kearena Chhim, Samsorphea Chhun, Wathanakpiseychoupoan Phirum, Sovann Nhoeung, Saren Sovann, Laurence Borand, Hyna Chea, Chantana Yay, Denis Laurent, Ousa Khan, and Bunnet Dim
Subjects: Microbiology (medical), Hepatitis B virus, medicine.medical_specialty, HBsAg, Mother to child transmission, Obstetrics, business.industry, virus diseases, General Medicine, Gold standard (test), equipment and supplies, medicine.disease_cause, digestive system diseases, Phnom penh, Infectious Diseases, parasitic diseases, medicine, business, Whole blood
Abstract: The objective is to assess the in-field performance of HBsAg whole blood rapid diagnosis test (RDT) as compared to plasmatic HBsAg RDT to diagnose HBV infection among pregnant women in Cambodia. Blood was collected on EDTA tubes from pregnant woman screened for the TA PROHM - ANRS 12345 study. Whole blood HBsAg RDT results were crossed compared with the plasmatic HBsAg RDT results, which was defined for this study as the gold standard. From December 2018 to May 2019, 4997 pregnant women were screened. The median age was 27.2 years old, 14% were screened in Phnom Penh and 86% in Siem Reap. Whole blood HBsAg RDT perform excellently with a sensitivity of 100% (95% CI, 98.7 – 100) and specificity of 100% (95% CI, 99.9 – 100). Whole blood HBs Ag RDT is as accurate as plasmatic one and could be used in remote areas.
Published: 2021

31. Escherichia coli ST410 among humans and the environment in Southeast Asia

Author: Laetitia Fabre, Marc Stegger, Agathe de Lauzanne, Maya Nadimpalli, Simon Le Hello, Jan Jacobs, Thierry Naas, Thong Phe, Laurence Borand, Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Sihanouk Hospital Center of HOPE [Phnom Penh], Institute of Tropical Medicine [Antwerp] (ITM), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre National de Référence - National Reference Center Escherichia coli, Shigella et Salmonella (CNR-ESS), Institut Pasteur [Paris], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Statens Serum Institut [Copenhagen], This work was supported by the Dennis and Mireille Gillings Foundation, Pasteur Foundation US and Institut Pasteur. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN)
Subjects: Male, 0301 basic medicine, medicine.disease_cause, Antimicrobial resistance, Genome, ST410, Cohort Studies, 0302 clinical medicine, Plasmid, Drug Resistance, Multiple, Bacterial, Environmental Microbiology, Pharmacology (medical), 030212 general & internal medicine, Replicon, Clade, Asia, Southeastern, Escherichia coli Infections, Phylogeny, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Genetics, Molecular Epidemiology, Phylogenetic tree, General Medicine, Middle Aged, Southeast Asia, 3. Good health, Infectious Diseases, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Adult, Microbiology (medical), clone (Java method), Genotype, 030106 microbiology, Biology, Polymorphism, Single Nucleotide, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Young Adult, 03 medical and health sciences, Antibiotic resistance, High-risk clone, medicine, Escherichia coli, Humans, Infant, Newborn, Infant, Sequence Analysis, DNA, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; Escherichia coli ST410 (Ec-ST410) is an emerging, multidrug-resistant clone. Recent investigations of its global epidemiology and evolution have been based almost exclusively on isolates from Europe and North America. It is unclear whether Southeast Asian-origin Ec-ST410 (SEA-Ec-ST410) belong to these same clones or represent regionally disseminated variants. Antimicrobial resistance mechanisms among SEA-Ec-ST410 were characterised, and whether they belonged to regional variants was investigated by contextualising them within a global collection. Seven Ec-ST410 were identified among a recent collection of expanded-spectrum cephalosporin-resistant E. coli recovered from 91 healthy women (stool) and 26 infected patients (blood and urine) living in Phnom Penh, Cambodia. Nine additional Ec-ST410 genomes were identified from Thailand (n = 7) and Vietnam (n = 2) through EnteroBase and PubMed searches. The assembled genomes were characterised and a SNP-based phylogenetic tree was created comparing these 16 SEA-Ec-ST410 with a previously published Ec-ST410 collection, primarily sourced from Europe (97/128) and North America (24/128). SEA-Ec-ST410 belonged to several distinct branches within previously described clonal clades. SEA-Ec-ST410 within the B3/H24Rx sublineage encoded blaCTX-M-55 (8/12) and F18:A-:B1 plasmid replicons (6/12), neither of which were detected among other Ec-ST410 belonging to this clade. Three of four SEA-Ec-ST410 within the B4/H24RxC sublineage lacked both blaOXA-181 and an IncX3 plasmid replicon that were harboured by 97% and 100% of all other Ec-ST410 in this sublineage (n = 64), respectively. In conclusion, Ec-ST410 are present in Southeast Asia following multiple introductions. The unique pattern of antimicrobial resistance elements harboured by SEA-Ec-ST410 suggests independent circulation in the region.
Published: 2019

32. Isolation of Nontuberculous Mycobacteria in Southeast Asian and African Human Immunodeficiency Virus-infected Children With Suspected Tuberculosis

Author: Christophe Delacourt, Ngoc Lan Nguyen, Sokleaph Cheng, Laurence Borand, Agathe de Lauzanne, Boubacar Nacro, Sylvain Godreuil, Philippe Msellati, Thu Hang Pham, Malin Inghammar, Abdoul-Salam Ouédraogo, Sara Eyangoh, Stéphane Blanche, Olivier Marcy, Vibol Ung, Bunnet Dim, Mathurin Cyrille Tejiokem, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), and Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: 0301 basic medicine, Microbiology (medical), nontuberculous mycobacteria, Tuberculosis, Isolation (health care), [SDV]Life Sciences [q-bio], 030106 microbiology, Human immunodeficiency virus (HIV), Mycobacterium Infections, Nontuberculous, HIV Infections, medicine.disease_cause, Southeast asian, 03 medical and health sciences, 0302 clinical medicine, children, parasitic diseases, medicine, Humans, Mycobacterium avium complex, 030212 general & internal medicine, Prospective Studies, Child, Immunodeficiency, Asia, Southeastern, biology, business.industry, Clinical Laboratory Techniques, Immunologic Deficiency Syndromes, virus diseases, HIV, biology.organism_classification, medicine.disease, Mycobacterium avium Complex, Virology, 3. Good health, Infectious Diseases, tuberculosis, Child, Preschool, Africa, Nontuberculous mycobacteria, Brief Reports, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: We enrolled 427 human immunodeficiency virus–infected children (median age, 7.3 years), 59.2% severely immunodeficient, with suspected tuberculosis in Southeast Asian and African settings. Nontuberculous mycobacteria were isolated in 46 children (10.8%); 45.7% of isolates were Mycobacterium avium complex. Southeast Asian origin, age 5–9 years, and severe immunodeficiency were independently associated with nontuberculous mycobacteria isolation. Clinical Trials Registration NCT01331811.
Published: 2019

33. A treatment-decision score for HIV-infected children with suspected tuberculosis

Author: Francis Ateba-Ndongo, Mathurin Cyrille Tejiokem, Bunnet Dim, Philippe Msellati, Duong Ngoc Tran, Laureline Berteloot, Bintou Sanogo, Isabelle Fournier, Stéphane Blanche, Catherine Quillet, Guislaine Carcelain, Laurence Borand, Sylvain Godreuil, Vibol Ung, Viet Do Chau, Khanh Truong Huu, Polidy Pean, Leakhena Neou, Suzie Tetang-Ndiang, Olivier Marcy, Christophe Delacourt, Boubacar Nacro, Sophie Goyet, Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Health Sciences [Phnom-Penh, Cambodia] (UHS), Tuberculosis and HIV Department [Phnom Penh, Cambodia], National pediatric hospital [Phnom Penh, Cambodge] (NPH), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Laboratoire d'Epidémiologie et de Santé Publique, Centre Pasteur du Cameroun, Benh Vien Nhi Dong 1 Children's Hospital [Vietnam], Pham Ngoc Thach Hospital, Centre Mère et Enfant de la Fondation Chantal Biya, Centre international de référence Chantal Biya pour la recherche sur la prévention et la prise en charge du VIH/SIDA (CIRCB), Fondation Chantal Biya (FCB)-Fondation Chantal Biya (FCB), Centre Hospitalier Essos [Yaoundé, Cameroun], Centre Hospitalier Universitaire Souro Sanou [Bobo-Dioulasso] (CHUSS), Unité d'Immunologie Hématologie et Rhumatologie Pédiatrique [Necker, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Angkor Hospital for Children (AHC), Immunologie [Phnom Penh], ANRS Research Site [Ho Chi Minh City, Vietnam], Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de radiologie pédiatrique [CHU Necker], Service Immunologie Biologique [Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Bactériologie-Virologie [Montpellier], Hôpital Arnaud de Villeneuve-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1), Service de Pneumologie et d'Allergologie Pédiatriques, Funded by the ANRS (ANRS 12229) and Fondation Total., and We thank all children and their parents and caregivers for their participation in the study, national tuberculosis and HIV programs from participating countries for their support, Françoise Barré-Sinoussi and Jean-François Delfraissy for their continuous support, Xavier Anglaret for general guidance, Julien Asselineau and Paul Perez for methodologic advice, and Corine Chazallon and Vincent Bouteloup for statistical support.
Subjects: Male, Pediatrics, medicine.medical_specialty, Miliary tuberculosis, Tuberculosis, Antitubercular Agents, Infectious Disease, HIV Infections, Sensitivity and Specificity, QuantiFERON, 03 medical and health sciences, 0302 clinical medicine, Tuberculosis diagnosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030225 pediatrics, Clinical Decision Rules, Abdomen, medicine, Humans, 030212 general & internal medicine, Child, Lung, Receptors, Interferon, Ultrasonography, Bacteriological Techniques, Microscopy, medicine.diagnostic_test, Receiver operating characteristic, AIDS-Related Opportunistic Infections, business.industry, Reproducibility of Results, medicine.disease, 3. Good health, Radiography, Abdominal ultrasonography, Child, Preschool, Pediatrics, Perinatology and Child Health, Commentary, HIV/AIDS, Female, Sample collection, business, Chest radiograph
Abstract: BACKGROUND: Diagnosis of tuberculosis should be improved in children infected with HIV to reduce mortality. We developed prediction scores to guide antituberculosis treatment decision in HIV-infected children with suspected tuberculosis. METHODS: HIV-infected children with suspected tuberculosis enrolled in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS 12229 PAANTHER 01 Study), underwent clinical assessment, chest radiography, Quantiferon Gold In-Tube (QFT), abdominal ultrasonography, and sample collection for microbiology, including Xpert MTB/RIF (Xpert). We developed 4 tuberculosis diagnostic models using logistic regression: (1) all predictors included, (2) QFT excluded, (3) ultrasonography excluded, and (4) QFT and ultrasonography excluded. We internally validated the models using resampling. We built a score on the basis of the model with the best area under the receiver operating characteristic curve and parsimony. RESULTS: A total of 438 children were enrolled in the study; 251 (57.3%) had tuberculosis, including 55 (12.6%) with culture- or Xpert-confirmed tuberculosis. The final 4 models included Xpert, fever lasting >2 weeks, unremitting cough, hemoptysis and weight loss in the past 4 weeks, contact with a patient with smear-positive tuberculosis, tachycardia, miliary tuberculosis, alveolar opacities, and lymph nodes on the chest radiograph, together with abdominal lymph nodes on the ultrasound and QFT results. The areas under the receiver operating characteristic curves were 0.866, 0.861, 0.850, and 0.846, for models 1, 2, 3, and 4, respectively. The score developed on model 2 had a sensitivity of 88.6% and a specificity of 61.2% for a tuberculosis diagnosis. CONCLUSIONS: Our score had a good diagnostic performance. Used in an algorithm, it should enable prompt treatment decision in children with suspected tuberculosis and a high mortality risk, thus contributing to significant public health benefits.
Published: 2019

34. Performance of Xpert MTB/RIF and Alternative Specimen Collection Methods for the Diagnosis of Tuberculosis in HIV-Infected Children

Author: Sara Eyangoh, Sophie Goyet, Arnaud Tarantola, Christophe Delacourt, Mathurin Cyrille Tejiokem, Abdoul-Salam Ouedraogo, Sokleaph Cheng, Laurence Borand, Boubacar Nacro, Sylvain Godreuil, Stéphane Blanche, Thu Hang Pham, Vibol Ung, Olivier Marcy, Philippe Msellati, Ngoc Lan Nguyen Thi, Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Pediatric Hospital, University of Health Sciences – Cambodia, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Pham Ngoc Thach Hospital, Centre Hospitalier Universitaire Souro Sanou [Bobo-Dioulasso] (CHUSS), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], and This work was supported by the French National Institute for Health and Medical Research (Inserm)–ANRS (ANRS 12194, ANRS 12229) and Fondation Total.
Subjects: Male, Bodily Secretions, MESH: Mycobacterium tuberculosis, diagnosis, HIV Infections, MESH: Bodily Secretions, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Nasopharyngeal aspirate, MESH: Child, Xpert MTBRIF, Medicine, MESH: Tuberculosis, Cameroon, 030212 general & internal medicine, Child, education.field_of_study, biology, Coinfection, MESH: Infant, Newborn, MESH: HIV Infections, MESH: Infant, 3. Good health, Infectious Diseases, tuberculosis, Vietnam, Specimen collection, Child, Preschool, Female, medicine.symptom, Cambodia, Nucleic Acid Amplification Techniques, DNA, Bacterial, Microbiology (medical), medicine.medical_specialty, Tuberculosis, Adolescent, Xpert MTB/RIF, Population, Sensitivity and Specificity, Specimen Handling, MESH: Nucleic Acid Amplification Techniques, Mycobacterium tuberculosis, 03 medical and health sciences, children, Tuberculosis diagnosis, 030225 pediatrics, Internal medicine, Burkina Faso, parasitic diseases, Humans, MESH: Burkina Faso, MESH: Specimen Handling, education, MESH: Adolescent, MESH: Humans, business.industry, MESH: Cambodia, MESH: Child, Preschool, Infant, Newborn, Infant, Nucleic acid amplification technique, MESH: Cameroon, HIV infection, biology.organism_classification, medicine.disease, MESH: DNA, Bacterial, MESH: Male, MESH: Sensitivity and Specificity, MESH: Coinfection, Surgery, Sputum, MESH: Vietnam, business, MESH: Female
Abstract: International audience; BACKGROUND:The diagnosis of tuberculosis in human immunodeficiency virus (HIV)-infected children is challenging. We assessed the performance of alternative specimen collection methods for tuberculosis diagnosis in HIV-infected children using Xpert MTB/RIF (Xpert).METHODS:HIV-infected children aged ≤13 years with suspected intrathoracic tuberculosis were enrolled in 8 hospitals in Burkina Faso, Cambodia, Cameroon, and Vietnam. Gastric aspirates were taken for children aged
Published: 2016

35. Serotype Distribution of Clinical Streptococcus pneumoniae Isolates before the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Cambodia

Author: Matthew R. Kasper, Vonthanak Saphonn, Arnaud Tarantola, Blandine Rammaert, Gavin W. Ford, Florence Komurian-Pradel, Paul Turner, Chadwick Y. Yasuda, Sok Touch, Alexandra Kerleguer, Christina Farris, Youlet By, Bertrand Guillard, Sirenda Vong, Laurence Borand, Buth Sokhal, Malin Inghammar, Jan Jacobs, Melina Messaoudi, Chanleakhena Phoeung, Thong Phe, Charles Mayaud, Ung Sam An, Sophie Goyet, Steven Newell, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Skane University Hospital [Lund], Fondation Mérieux, University of Health Science, US Naval Medical Research Unit n°2, Shihanouk Hospital Centre of HOPE, Médecine Interne et Maladies Infectieuses, CHU de Poitiers, Poitiers, France, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Cambodian National Laboratory of Public Health, Communicable Disease Department [Phnom Penh] (CDC MOH), Ministry of Health [Mozambique], Cambodia Oxford Medical Research, Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Institute of Tropical Medicine [Antwerp] (ITM), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nuffield Department of Clinical Medicine [Oxford], University of Oxford, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Tarantola, Arnaud
Subjects: Male, 0301 basic medicine, Serotype, [SDV]Life Sciences [q-bio], Drug resistance, medicine.disease_cause, Pneumococcal conjugate vaccine, Pneumococcal Vaccines, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Resistance, Multiple, Bacterial, Medicine, 030212 general & internal medicine, Child, Aged, 80 and over, Articles, Middle Aged, Anti-Bacterial Agents, Bacterial Typing Techniques, 3. Good health, [SDV] Life Sciences [q-bio], Streptococcus pneumoniae, Infectious Diseases, Child, Preschool, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, medicine.symptom, Cambodia, Bronchoalveolar Lavage Fluid, medicine.drug, Adult, Adolescent, 030106 microbiology, Serogroup, Mass Vaccination, 03 medical and health sciences, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Antibiotic resistance, Virology, Multiplex polymerase chain reaction, Humans, Aged, Vaccines, Conjugate, business.industry, Sputum, Infant, Pneumonia, Pneumococcal, Laboratories, Hospital, medicine.disease, Pneumonia, Parasitology, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business
Abstract: International audience; Childhood vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in Cambodia in January 2015. Baseline data regarding circulating serotypes are scarce. All microbiology laboratories in Cambodia were contacted for identification of stored isolates ofStreptococcus pneumoniaefrom clinical specimens taken before the introduction of PCV13. Available isolates were serotyped using a multiplex polymerase chain reaction method. Among 166 identified isolates available for serotyping from patients with pneumococcal disease, 4% were isolated from upper respiratory samples and 80% were from lower respiratory samples, and 16% were invasive isolates. PCV13 serotypes accounted for 60% (95% confidence interval [CI] 52-67) of all isolates; 56% (95% CI 48-64) of noninvasive and 77% (95% CI 57-89) of invasive isolates. Antibiotic resistance was more common among PCV13 serotypes. This study of clinicalS. pneumoniaeisolates supports the potential for high reduction in pneumococcal disease burden and may serve as baseline data for future monitoring ofS. pneumoniaeserotypes circulation after implementation of PCV13 childhood vaccination in Cambodia.
Published: 2018

36. Complete Genome Sequence of

Author: Amar, Bouam, Anthony, Levasseur, Maryline, Bonnet, Laurence, Borand, Charles, Van Goethem, Michel, Drancourt, and Sylvain, Godreuil
Subjects: Prokaryotes
Abstract: Mycobacterium sp. strain 4858 is a nontuberculous mycobacterium isolated from sputum in a Cambodian patient with a pulmonary infection. We report the first complete 5.6-Mbp-long genome sequence of Mycobacterium strain 4858, with 68.24% GC content, carrying 5,255 protein-coding genes, 47 tRNAs, and 3 rRNA genes.
Published: 2018

37. Community-acquired pneumonia and Gram-negative bacilli in Cambodia—incidence, risk factors and clinical characteristics

Author: Sirenda Vong, Laurence Borand, Blandine Rammaert, Philippe Buchy, Vantha Te, Charles Mayaud, Bertrand Guillard, Sophie Goyet, Arnaud Tarantola, Eap Tek Chheng, Malin Inghammar, Philippe Cavailler, Patrich Lorn Try, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Lund University [Lund], Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Takeo Provincial Hospital, Kampong Cham Provincial hospital, Kampong Cham Provincial hospital [Cambodia], GlaxoSmithKline, Glaxo Smith Kline, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This study was part of the Surveillance and Investigation of epidemic situations in South-East Asia (SISEA) project, which was funded by the French Agency for Development and the US Department of Human and Health Services. Malin Inghammar received grants from the Swedish Society of Medicine and Swedish governmental funds., and The datasets generated and/or analysed during the current study are not publicly available but are available from the corresponding author on reasonable request.
Subjects: Male, Gram-negative bacilli, Epidemiology, Drug resistance, Logistic regression, 0302 clinical medicine, Community-acquired pneumonia, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Prospective Studies, 030212 general & internal medicine, Community acquired, Prospective cohort study, education.field_of_study, Incidence, Incidence (epidemiology), General Medicine, Middle Aged, Anti-Bacterial Agents, 3. Good health, Community-Acquired Infections, Treatment Outcome, Infectious Diseases, Female, Cambodia, Adult, medicine.medical_specialty, Population, Young Adult, 03 medical and health sciences, Internal medicine, Pseudomonas, Drug Resistance, Bacterial, Gram-Negative Bacteria, Pneumonia, Bacterial, medicine, Humans, education, Aged, business.industry, Public Health, Environmental and Occupational Health, Original Articles, Pneumonia, medicine.disease, 030228 respiratory system, Parasitology, Gram-Negative Bacterial Infections, business
Abstract: International audience; Background:In Western settings, community-acquired pneumonia (CAP) due to Gram-negative bacilli (GNB) is relatively rare. Previous studies from Asia, however, indicate a higher prevalence of GNB in CAP, but data, particularly from Southeast Asia, are limited.Methods:This is a prospective observational study of 1451 patients ≥15 y of age with CAP from two hospitals in Cambodia between 2007 and 2010. The proportion of GNB was estimated. Risk factors and clinical characteristics of CAP due to GNB were assessed using logistic regression models.Results:The prevalence of GNB was 8.6% in all CAP patients and 15.8% among those with a valid respiratory sample. GNB infection was independently associated with diabetes, higher leucocyte count and CAP severity. Mortality was higher in patients with CAP due to GNB.Conclusions:We found a high proportion of GNB in a population hospitalized for CAP in Cambodia. Given the complex antimicrobial sensitivity patterns of certain GNBs and the rapid emergence of multidrug-resistant GNB, microbiological laboratory capacity should be strengthened and prospective clinical trials comparing empiric treatment algorithms according to the severity of CAP are needed
Published: 2018

38. Mortality and its determinants in antiretroviral treatment-naive HIV-infected children with suspected tuberculosis: an observational cohort study

Author: Olivier Marcy, Mathurin Tejiokem, Philippe Msellati, Khanh Truong Huu, Viet Do Chau, Duong Tran Ngoc, Boubacar Nacro, Francis Ateba-Ndongo, Suzie Tetang-Ndiang, Vibol Ung, Bunnet Dim, Leakhena Neou, Laureline Berteloot, Laurence Borand, Christophe Delacourt, Stéphane Blanche, Sao Sarady Ay, Malen Chan, Phalla Chea, Sophie Goyet, Nimul Roat Men, Phearavin Pheng, Susan Ramsay, Sophea Suom, Arnaud Tarantola, Naisim Te, Sreymom Than, Sovannary Ung, Chorn Chhuk, Chantheany Huot, Sang Han Kath, Sokoeun Khin, Peou Kim, Kim Eng Lim, Phary Lim, Vannareth Lim, Yany Nav, Boren Pich, Sotharin Tuy, Phal Chea, Sengtray Chhraing, Bophal Chuop, Ramy Hem, Phanoeurn Heng, Seng Hap Huon, Sokhorn Khum, Thear Liv, Vichea Ly, Makara Moch, Leakheana Neou, Phanith Rey, Vina Sath, Nopheavann Sun, Pheron Chat, Viso Srey, Sitha Chheang, Putchhat Hor, Manory Oum, Monorea Keo, Sokchea Kou, Sokleaph Cheng, Alexandra Kerleguer, Michel Gomgnimbou, Antoinette Kabore, Anselme Millogo, Zakari Nikiema, Abdul Salam Ouedraogo, Sawadogo Saidou, Moumini Nouctara, Diane Ursule Sangare/Ouattara, Bintou Sanogo, Edgard Sib Sié, Dézémon Zingué, Roger Ngoya Abiguide, Patrice Assene Ngo'o, Francis Ateba Ndongo, Suzanne Balla, Verlaine Bolyse Mbouchong, Jean Marie Ehongo Amanya, Sara Eyangoh, Afi Leslie Kaiyven, Paul Koki Ndombo, Samuel Walter Kokola Bayanak, Marie Josée Mapah Kampaing, Elizabeth Mangoya, Minkala Mvogo, Jean Pierre Ndongo, Laurence Ngassam, Francine Nanda, Sylviane Ndjantou, Jean Audrey Ndongo, Marcelle Njind Nkoum, Anne Esther Njom Lend, Angeline Nkembe, Marie Flore Oyanche, Jean-Voisin Taguebue, Suzy Tetang-Moyo, Sylvie Georgette Zebaze, Thi Oanh Nguyen, Thi Ngoc Lan Nguyen, Catherine Quillet, Khanh Lê Quoc, My Huong To, Thi Kim Phung Tran, Chau Giang Do, Duc Bang Nguyen, Ngo Vi Vi Nguyen, Thi Hieu Nguyen, Thi Thanh Thanh Nguyen, Ngoc Duong Tran, Duy An Vo, Thi Xuan Lan Dang, Thi Kim Phuong Do, Thi Thanh Tuyen Dang, Hoang Chau Nguyen, Ngoc Tuong Vy Pham, Huu Khanh Truong, Chau Viet Do, Bich Ngoc Huynh, Thi Thanh Thuy Le, Thi Thu Hiep Nguyen, Ngoc Luu Tran, Thien An Vu, Huu Loc Tran, Manh Hoang Nguyen, Ngoc Lan Nguyen, Thi Cao Van Nguyen, Thu Hang Pham, Dinh Quyen Phan, Thi Ha Vo, Xuan Lien Truong, Xuan Thinh Vu, Guislaine Carcelain, Sylvain Godreuil, Isabelle Fournier-Nicolle, Institut Pasteur du Cambodge, Institut Pasteur du Cambodge-Réseau International des Instituts Pasteur ( RIIP ), Bordeaux population health ( BPH ), Université de Bordeaux ( UB ) -Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Pasteur du Cameroun, Centre Pasteur du Cameroun-Réseau International des Instituts Pasteur ( RIIP ), Recherches Translationnelles sur le VIH et les maladies infectieuses ( TransVIHMI ), Université Montpellier 1 ( UM1 ) -Université Cheikh Anta Diop ( UCAD ) -Universtié Yaoundé 1 (Cameroun)-Université de Montpellier ( UM ), Service de radiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Pneumologie Allergologie [CHU Necker], Service d'immunologie, hématologie et rhumatologie pédiatriques [CHU Necker], Réseau International des Instituts Pasteur (RIIP), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Service d'immuno-hématologie pédiatrique [CHU Necker]
Subjects: Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Tuberculosis, Adolescent, Anti-HIV Agents, Epidemiology, 030106 microbiology, Immunology, Antitubercular Agents, HIV Infections, Kaplan-Meier Estimate, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Hiv infected, Burkina Faso, medicine, Antiretroviral treatment, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Cameroon, 030212 general & internal medicine, Mortality, Child, Coinfection, business.industry, medicine.disease, 3. Good health, Clinical trial, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Vietnam, Child, Preschool, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Observational study, Cambodia, business, Cohort study
Abstract: International audience; BACKGROUND:Tuberculosis is a major cause of morbidity and mortality in HIV-infected children, but is difficult to diagnose. We studied mortality and its determinants in antiretroviral treatment (ART)-naive HIV-infected children presenting with suspected tuberculosis.METHODS:In this observational cohort study, HIV-infected children aged 13 years or younger with suspected tuberculosis were followed up for 6 months as part of the ANRS 12229 PAANTHER 01 cohort in eight hospitals in four countries (Burkina Faso, Cambodia, Cameroon, and Vietnam). Children started ART and antituberculosis treatment at the clinician's discretion and were retrospectively classified into one of three groups by tuberculosis documentation: confirmed by culture or Xpert MTB/RIF, unconfirmed, and unlikely. We assessed mortality and associated factors using Kaplan-Meier methods and Cox proportional hazard models. The ANRS 12229 PAANTHER 01 study is registered at ClinicalTrials.gov, number NCT01331811.FINDINGS:266 (61%) of 438 children enrolled in the study between April 27, 2011, and May 31, 2014, were ART-naive and included in the analysis (40 had confirmed tuberculosis, 119 unconfirmed tuberculosis, and 107 unlikely tuberculosis). 112·5 person-years of follow-up were available. 154 children (58%) started antituberculosis treatment and 212 (80%) started ART. 50 children (19%) died. Mortality by 6 months was higher in children with confirmed tuberculosis (14 deaths; 2 month survival probability 65·0% [95% CI 50·2-79·8]) compared with unconfirmed tuberculosis (19 deaths; 83·5% [76·8-90·3]) and unlikely tuberculosis (17 deaths; 83·5% [76·3-90·7]; log-rank p=0·0141) and was lower in children with confirmed or unconfirmed tuberculosis who started antituberculosis treatment (p
Published: 2018

39. Extended Spectrum β-Lactamase-Producing Enterobacteriaceae among Meat, Fish, and Healthy Mothers in Phnom Penh, Cambodia

Author: Maya Nadimpalli, Malika Gouali, Simon Le Hello, Laurence Borand, Kruy Sun Lay, Yith Vuthy, Laetitia Fabre, Elisabeth Delarocque-Astagneau, Agathe de Lauzanne, and Bich-Tram Huynh
Subjects: Phnom penh, Veterinary medicine, General Earth and Planetary Sciences, %22">Fish , Biology, biology.organism_classification, Enterobacteriaceae, General Environmental Science
Published: 2018

40. Complete genome sequence of Mycobacterium sp. Strain 4858

Author: Amar Bouam, Anthony Levasseur, Maryline Bonnet, Laurence Borand, Charles Van Goethem, Michel Drancourt, Sylvain Godreuil, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: 0303 health sciences, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 0206 medical engineering, education, Genetics, 02 engineering and technology, Molecular Biology, 020602 bioinformatics, 030304 developmental biology
Abstract: Mycobacterium sp. strain 4858 is a nontuberculous mycobacterium isolated from sputum in a Cambodian patient with a pulmonary infection. We report the first complete 5.6-Mbp-long genome sequence of Mycobacterium strain 4858, with 68.24% GC content, carrying 5,255 protein-coding genes, 47 tRNAs, and 3 rRNA genes.
Published: 2018

41. Necrotic Tuberculin Skin (Mantoux) Test Reaction

Author: Alexandra Kerleguer, Laurence Borand, Viseth Phuong, Yiksing Peng, Peou Kim, Polidy Pean, Dim Bunnet, Nayyim Heng, and Arnaud Tarantola
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Necrosis, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Tuberculin, Mantoux test, Critical Care and Intensive Care Medicine, Dermatology, 3. Good health, Surgery, Vaccination, Lesion, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Active tb, medicine, 030212 general & internal medicine, Necrotic Lesion, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: Tuberculin skin testing was performed on a 5-year-old girl in Phnom Penh, Cambodia. She had been immunized by Bacille de Calmette et Guerin. She was tested because of a palpable cervical node and a slightly elevated temperature. Within 48 h, a deep necrotic lesion appeared on the volar aspect of the left arm. The lesion was treated locally, and the child was not treated for suspected TB. To our knowledge, this is the first instance of necrosis in 11,392 people who received Tubersol doses since 1996 to date at our International Vaccination Center, for an estimated incidence of 0.18 per 1,000 (95% Poisson 0.04-0.70 per 1,000 doses used). At a follow-up consultation after 77 days, the lesion had scarred and the child showed no signs suggestive of active TB. Although latent TB infection remains the most likely diagnosis, other types of mycobacterial infection may be considered in the tropical setting and in the absence of signs suggestive of active TB.
Published: 2015

42. Interleukin-1 receptor antagonist, a biomarker of response to anti-TB treatment in HIV/TB co-infected patients

Author: Daniel Scott-Algara, Yoann Madec, Didier Laureillard, Polidy Pean, François-Xavier Blanc, Janin Nouhin, Céline Didier, Mathieu F. Chevalier, Laurence Weiss, Laurence Borand, VIH/Hépatites, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université Paris Diderot - Paris 7 (UPD7), Immunologie [Phnom Penh], Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Régulation des Infections Rétrovirales, Institut Pasteur [Paris], Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Centre hospitalier universitaire de Nantes (CHU Nantes), Service des maladies infectieuses et tropicales, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Sorbonne Paris Cité (USPC), This work was supported by ARI (Association pour la Recherche en Immunopathologie)., We thank all the patients who participated in the study. We also thank the ANRS for authorizing us to use the biobank of CAMELIA and CAPRI-NK for this work., Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, Male, Multivariate analysis, MESH: Immune Reconstitution Inflammatory Syndrome*/complications, MESH: Immune Reconstitution Inflammatory Syndrome*/blood, MESH: Biomarkers/blood, [SDV]Life Sciences [q-bio], MESH: Tuberculosis*/complications, Antitubercular Agents, HIV Infections, urologic and male genital diseases, MESH: Tuberculosis*/blood, 0302 clinical medicine, Immune Reconstitution Inflammatory Syndrome, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Macrophage, 030212 general & internal medicine, Randomized Controlled Trials as Topic, MESH: Case-Control Studies, female genital diseases and pregnancy complications, 3. Good health, TB-IRIS, Infectious Diseases, medicine.anatomical_structure, MESH: Tuberculosis*/drug therapy, Biomarker (medicine), Female, Fresh frozen plasma, Cambodia, MESH: Immune Reconstitution Inflammatory Syndrome*/diagnosis, Microbiology (medical), Adult, IL-1 receptor antagonist, MESH: Tuberculosis*/diagnosis, 03 medical and health sciences, Immune reconstitution inflammatory syndrome, medicine, Humans, Tuberculosis, Anti-tuberculosis treatment, cardiovascular diseases, HIV/tuberculosis co-infection, MESH: Humans, MESH: HIV Infections/complications, business.industry, urogenital system, Monocyte, fungi, MESH: Adult, medicine.disease, MESH: Antitubercular Agents/therapeutic use, MESH: Male, Interleukin 1 Receptor Antagonist Protein, 030104 developmental biology, Interleukin 1 receptor antagonist, MESH: Randomized Controlled Trials as Topic, Case-Control Studies, Immunology, MESH: Interleukin 1 Receptor Antagonist Protein/blood, business, Tb treatment, MESH: Female, Biomarkers
Abstract: International audience; OBJECTIVES: Despite the high frequency of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in human immunodeficiency virus (HIV)/TB co-infected patients, no diagnostic test is available. Here, we investigated whether monocyte/macrophage activation markers can predict TB-IRIS occurrence and if they are modulated by anti-TB treatment.METHODS: Frozen plasma was obtained from 127 HIV/TB co-infected adults naïve for antiretroviral therapy, enrolled in the CAMELIA trial, 36 of whom developed TB-IRIS. Concentrations of IL-1Ra, sCD14, and sCD163 were measured at anti-TB treatment onset (baseline), after 8 weeks of anti-TB treatment and at TB-IRIS time.RESULTS: At baseline, IL-1Ra and sCD14 concentrations were similar in TB-IRIS and non-IRIS patients. sCD163 concentrations, although significantly higher in TB-IRIS patients, did not remain associated with TB-IRIS occurrence in multivariate analysis. At the time of TB-IRIS, patients displayed higher concentrations of IL-1Ra (p = 0.002) and sCD14 (p < 0.001). The most striking result was the significant decrease in IL-1Ra after 8 weeks of anti-TB treatment (median reduction: -63% (p < 0.0001)).CONCLUSIONS: None of the biomarkers tested was associated with TB-IRIS occurrence. However, repeated measurement of IL-1Ra could help for the diagnosis of TB-IRIS. The substantial reduction of IL-1Ra under treatment suggests that IL-1Ra could be a surrogate biomarker of anti-TB treatment response in HIV-infected patients.
Published: 2017

43. Causes and Determinants of Mortality in HIV-Infected Adults With Tuberculosis: An Analysis From the CAMELIA ANRS 1295-CIPRA KH001 Randomized Trial

Author: Anne E. Goldfeld, Thim Sok, Chindamony Kim, Laurence Borand, Charles Mayaud, Bunnet Dim, Yoann Madec, François-Xavier Blanc, Didier Laureillard, Olivier Marcy, Jean-François Delfraissy, Kim Khemarin Lak, Narom Prak, Sarin Chan, Chanroeurn Hak, Boutin, Marion, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Cambodian Health Committee, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Khmero-Sovietic Friendship Hospital, Donkeo Provincial Hospital, Calmette Hospital [Phnom Penh], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Harvard Medical School [Boston] (HMS), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), This work was supported by the French NationalAgency for Research on AIDS and Viral Hepatitis (ANRS 1295) and theUS National Institutes of Health (NIH), Division of AIDS (CIPRAKH001/DAID-ES ID 10425)., Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX)
Subjects: Male, Microbiology (medical), Pediatrics, medicine.medical_specialty, Tuberculosis, Anti-HIV Agents, medicine.medical_treatment, Antitubercular Agents, HIV Infections, law.invention, Cohort Studies, Immunocompromised Host, cause of death, Anti-Infective Agents, Randomized controlled trial, Tuberculosis diagnosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Antiretroviral Therapy, Highly Active, Trimethoprim, Sulfamethoxazole Drug Combination, medicine, Humans, Cause of death, business.industry, adult, Mortality rate, HIV, Immunosuppression, medicine.disease, mortality, CD4 Lymphocyte Count, 3. Good health, Infectious Diseases, tuberculosis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Etiology, HIV/AIDS, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Follow-Up Studies, Cohort study
Abstract: Despite advances in tuberculosis diagnosis and access to treatment for human immunodeficiency virus (HIV) infection, tuberculosis remains a major cause of death in HIV-infected patients [1, 2]. In 2012, it was estimated that 1.0–1.2 million new tuberculosis cases and 0.32 million tuberculosis-related deaths occurred in HIV-infected persons, accounting for 13% of the global tuberculosis burden and 25% of tuberculosis mortality [1]. Several randomized clinical trials showed the positive impact upon mortality of shortening the delay between tuberculosis treatment onset and initiation of antiretroviral therapy (ART) [3–7]. The level of immunosuppression [3, 4] and the location or severity of tuberculosis disease [6] have been reported to impact the survival benefit gained from earlier ART initiation [3–7]. Notably, in general, data are scarce on tuberculosis-related factors associated with mortality in HIV-infected adults treated for tuberculosis. Observational and autopsy studies showed that tuberculosis itself constitutes the principal cause of death [8–10], but other HIV-related opportunistic infections are frequently reported as the etiology of death. Thus, a deeper understanding of the causes and factors associated with death is needed to develop strategies aiming to further reduce mortality in HIV-infected patients treated for tuberculosis. Here, we assessed mortality rates, causes, and risk factors of death in HIV-infected patients enrolled in the CAMELIA (Cambodian Early vs Late Introduction of Antiretroviral Therapy) randomized clinical trial. We specifically analyzed (1) early deaths before 26 weeks of follow-up (W26), where mortality is thought to be mainly linked to the severity of initial presentation and expected to be related to HIV and tuberculosis; and (2) late deaths after 50 weeks of follow-up (W50), at a time when most patients would be expected to have been cured from their tuberculosis and to have recovered a level of protective immunity in general [11, 12].
Published: 2014

44. Bacterial neonatal sepsis and antibiotic resistance in low-income countries

Author: Bich-Tram Huynh, Michael Padget, Benoit Garin, Elisabeth Delarocque-Astagneau, Didier Guillemot, Laurence Borand, Thida Chon, Agathe de Lauzanne, Sophie Goyet, Sopheak Hem, Alexandra Kerleguer, Siyin Lach, Veronique Ngo, Arnaud Tarantola, Sok Touch, Jean-Marc Collard, Perlinot Herindrainy, Patrice Piola, Bodonirina Tanjona Raheliarivao, Frédérique Randrianirina, Awa Ndir, Vincent Richard, Abdoulaye Seck, Raymond Bercion, Amy Gassama Sow, Jean Baptiste Diouf, Pape Samba Dieye, Balla Sy, Bouya Ndao, Maud Seguy, Elsa Kermorvant-Duchemin, Laurence Watier, Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Prévention et Thérapie Moléculaires des Maladies Infectieuses Humaines, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hôpital Raymond Poincaré [AP-HP], BIRDY study group : Cambodia : Laurence Borand, PharmD PhD, Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Thida Chon, midwife, Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Agathe de Lauzanne, MD MPH, Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Sophie Goyet, midwife PhD, Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Sopheak Hem, Medical Biologist (Medical Laboratory– Institut Pasteur du Cambodge, Phnom Penh, Cambodia), Alexandra Kerleguer, MD Medical Biologist (Head of Medical Laboratory – Institut Pasteur du Cambodge, Phnom Penh, Cambodia), Siyin Lach, Midwife, Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Veronique Ngo, midwife, Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Arnaud Tarantola, MD PhD, Head of Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Sok Touch, MD MPH (retired) Director of CDC (Communicable Disease Department) Department at Ministry of Health Cambodia. Madagascar : Jean-Marc Collard, PhD, Experimental bacteriology unit, Institut Pasteur Madagascar, Perlinot HERINDRAINY, MD MPH, Epidemiology & Public Health Unit, Institut Pasteur Madagascar, Patrice Piola, MD PhD, Epidemiology & Public Health Unit, Institut Pasteur Madagascar Bodonirina Tanjona RAHELIARIVAO, MD, Epidemiology & Public Health Unit, Institut Pasteur Madagascar, Frédérique RANDRIANIRINA, MD, Centre de Biologie Clinique, Institut Pasteur Madagascar. Senegal : Awa Ndir, PhD, Institut Pasteur de Dakar, Vincent Richard, MD MPH, Institut Pasteur de Dakar, Abdoulaye Seck, PharmD, Institut Pasteur de Dakar, Raymond Bercion, MD, Institut Pasteur de Dakar, Amy GASSAMA SOW, PhD, Institut Pasteur de Dakar, Jean Baptiste DIOUF, MD, Hôpital Roi Baudoin, Pape Samba DIEYE, MD, District Sanitaire de Guédiawaye, Balla SY, MD, District Sanitaire de Sokone Bouya NDAO, MD, District Sanitaire de Sokone, France Maud Seguy, PhD, Department of International Affairs, Institut Pasteur Paris, Elsa Kermorvant-Duchemin, MD PhD, AP-AP, Hôpital Universitaire Necker-Enfants malades, Department of Neonatology, Paris 75015, France-Université Paris Descartes, Faculté de médecine, Paris 75006, Laurence Watier, PhD, Inserm UMR 1181 « Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases » (B2PHI), F-75015 Paris, France-Institut Pasteur, UMR 1181, B2PHI, 75015 Paris., Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, medicine.medical_specialty, MESH: Drug Resistance, Microbial, MESH: Poverty, MEDLINE, Developing country, Drug resistance, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Antibiotic resistance, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Medicine, 030212 general & internal medicine, Intensive care medicine, Poverty, MESH: Sepsis, ComputingMilieux_MISCELLANEOUS, MESH: Humans, Neonatal sepsis, business.industry, MESH: Infant, Newborn, Infant, Newborn, Drug Resistance, Microbial, General Medicine, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Infant newborn, 030104 developmental biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience
Published: 2016

45. Co-infection tuberculose et VIH

Author: Manil Saman, Olivier Marcy, Sophea Suom, Phalla Chea, Nimul Roat Men, Eric Nerrienet, Phearavin Pheng, Chanthy Leng, Sao Sarady Ay, and Laurence Borand
Subjects: medicine.medical_specialty, Pediatrics, Tuberculosis, business.industry, Public health, Human immunodeficiency virus (HIV), MEDLINE, virus diseases, General Medicine, medicine.disease, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, law.invention, Randomized controlled trial, law, parasitic diseases, medicine, Coinfection, business, Cause of death
Abstract: Tuberculosis is a major cause of death among adults infected by HIV. The CAMELIA (ANRS 1295/CIPRA KH001) randomized clinical trial aimed to determine the optimal timing of ARV initiation after tuberculosis treatment onset to reduce mortality. Here, we describe the trial implementation in five hospitals in Cambodia under the coordination of the Institut Pasteur in Cambodia, its conduct, the challenges and public health benefits in Cambodia and beyond.
Published: 2013

46. The ethics of a clinical trial when the protocol clashes with international guidelines [Unresolved issues]

Author: Christian Lienhardt, Alexander S. Pym, Truong Xuan Lien, N. H. Dung, C. Quillet, Catherine Connolly, A-M. Taburet, Anthony D. Harries, N. H. Duc, N. T. N. Lan, D. Lagarde, Laurence Borand, C. Rekacewicz, N. N. Lan, N. T. N. Thu, and D. Laureillard
Subjects: Protocol (science), medicine.medical_specialty, Operations research, business.industry, Health Policy, Best practice, education, Public Health, Environmental and Occupational Health, Human immunodeficiency virus (HIV), Alternative medicine, medicine.disease_cause, Antiretroviral therapy, Scientific evidence, Clinical trial, Regimen, Family medicine, medicine, business
Abstract: Due to their nature and complexity, clinical trials often take some time to launch after the protocol has been designed and ethics approval obtained. During this time, there may be changes in international treatment guidelines and recommendations that result in a conflict between study protocol and recommended international best practice. Here, we describe the situation that arose in a pharmacokinetic study on the use of two different doses of rifabutin in patients with human immunodeficiency virus-associated tuberculosis who initiated antiretroviral therapy (ART) with a lopinavir-ritonavir-based regimen in South Africa and Viet Nam. The study protocol specified that ART should be started 10 weeks after the start of anti-tuberculosis treatment. The study in South Africa was approved in June 2008, went ahead as scheduled and was completed in August 2010. The study in Viet Nam was approved in October 2008 and was started in June 2010. A few weeks later, the World Health Organization released their 2010 guidelines for adult ART; one of its strong recommendations (with moderate quality of evidence) was that ART should be started 2-8 weeks after the start of anti-tuberculosis treatment. Emerging scientific evidence also supported this recommendation. The investigators felt that the Viet Nam study protocol was in conflict with recommended international best practice, and the trial was stopped in October 2010. An amended study protocol in which ART was started at 2 weeks was developed and implemented. The ethics issues around this decision and the need to change the study protocol are discussed in this article.
Published: 2013

47. A Study of the Genetic Variability of Human Respiratory Syncytial Virus (HRSV) in Cambodia Reveals the Existence of a New HRSV Group B Genotype

Author: Sirenda Vong, Laurence Borand, Sareth Rith, Vincent Deubel, Roger Frutos, Philippe Buchy, Alicia Arnott, Nima Asgari, Sok Touch, Ly Sovann, Bertrand Guillard, Sek Mardy, Monica Naughtin, Julien Beauté, Simon Chu, and Carole Buecher
Subjects: Adult, Male, Microbiology (medical), Adolescent, Genotype, Epidemiology, Molecular Sequence Data, Population, Respiratory Syncytial Virus Infections, Biology, Group B, Virus, Young Adult, medicine, Cluster Analysis, Humans, Genetic variability, Child, education, Phylogeny, Aged, Aged, 80 and over, Molecular Epidemiology, education.field_of_study, Molecular epidemiology, Age Factors, Infant, Newborn, Genetic Variation, Infant, Sequence Analysis, DNA, Middle Aged, medicine.disease, Virology, Pneumonia, Bronchiolitis, Child, Preschool, Respiratory Syncytial Virus, Human, Immunology, RNA, Viral, Female, Seasons, Cambodia
Abstract: Human respiratory syncytial virus (HRSV) is the leading cause of hospitalization of children aged
Published: 2011

48. Fluoroquinolone resistance and Mycobacterium tuberculosis: CAP guidelines play an important role

Author: Laurence Borand, Kruy Lim, Johan van Griensven, Arnaud Tarantola, Phe Thong, Olivier Marcy, Erika Vlieghe, Sophie Goyet, and Blandine Rammaert
Subjects: Pulmonary and Respiratory Medicine, Tuberculosis, biology, business.industry, medicine.drug_class, Antibiotics, Drug resistance, biology.organism_classification, medicine.disease, Virology, Fluoroquinolone resistance, Microbiology, Penicillin, Mycobacterium tuberculosis, Pneumonia, Infectious Diseases, Medicine, Medical prescription, business, medicine.drug
Published: 2014

49. TB-IRIS, T-cell activation, and remodeling of the T-cell compartment in highly immunosuppressed HIV-infected patients with TB

Author: Viraga Haridas, Yoann Madec, Thim Sok, Anne E. Goldfeld, Didier Laureillard, Laurence Borand, Olivier Marcy, Sun Sath, Jean-François Delfraissy, Polidy Pean, François-Xavier Blanc, Sarin Chan, Erdyni N. Tsitsikov, Luke D. Jasenosky, Harvard Medical School [Boston] (HMS), Boston Children's Hospital, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Cambodian Health Committee, Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), This work was supported by grants from the ANRS (12164), the NIH (R21AI076023), the Annenberg Foundation, AERAS, and AmFAR, with support from NIAID/NIH-IeDEA (U01AI069907–07), and a gift from John Moores., Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Boutin, Marion
Subjects: Male, T-Lymphocytes, medicine.medical_treatment, Antitubercular Agents, HIV Infections, MESH: Flow Cytometry, MESH: Tuberculosis/drug therapy, Immune Reconstitution Inflammatory Syndrome, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunopathology, Immunology and Allergy, Cytotoxic T cell, Prospective Studies, MESH: Anti-Retroviral Agents/therapeutic use, MESH: Treatment Outcome, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: HIV Infections/drug therapy, Interleukin, MESH: T-Lymphocytes/immunology, Flow Cytometry, 3. Good health, Treatment Outcome, Infectious Diseases, Cytokine, medicine.anatomical_structure, Anti-Retroviral Agents, MESH: Tuberculosis/pathology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cytokines, Female, MESH: Tuberculosis/immunology, Cambodia, Viral load, Adult, MESH: Immunophenotyping, T cell, Immunology, Biology, Article, Immunophenotyping, Immune system, Immune reconstitution inflammatory syndrome, MESH: Immune Reconstitution Inflammatory Syndrome/immunology, medicine, Humans, Tuberculosis, MESH: Immune Reconstitution Inflammatory Syndrome/pathology, MESH: Humans, MESH: HIV Infections/complications, MESH: Cambodia, MESH: Adult, medicine.disease, MESH: Antitubercular Agents/therapeutic use, MESH: Male, MESH: Prospective Studies, MESH: HIV Infections/immunology, MESH: Cytokines/metabolism, MESH: Female
Abstract: The authors are indebted to Wallis Annenberg whose generosity made this study possible, and to John Moores for his generous gift. We are grateful to Francoise Barré-Sinoussi for her help, advice, and support over the years. We thank Eric Nerrienet, Claire Rekacewicz, Daniel Scott, Gianfranco Pancino, Jean-Louis Sarthou, and Charles Mayaud for helpful discussions and advice as we began the study, and Jean-Louis Sarthou for his long time support of the Harvard team’s collaboration with the Institut Pasteur du Cambodge. We thank the CAMELIA study team, including the site nurses, doctors, and health workers, and Vincent Deubel and the staff at the Institut Pasteur du Cambodge. We thank Larry Fox, Rod Hoff, Jane Bupp, and Brigitte Bazin for their support and helpful discussions from the beginning of CAMELIA onward and the staff of the Cambodian Health Committee, especially Sam Sophan, for his contributions to and support of the work. We thank Leslie Kalish of Children’s Hospital Boston and the Harvard Catalyst Biostatistical Consulting program (NIH UL1 TR001102) for expert statistical advice and help as we started the analysis. We also thank Jerry Sadoff for his early support and Judy Lieberman for helpful comments on the manuscript. Finally, we are deeply indebted to the patients who took part in this study, who generously offered their participation to help the scientific community find solutions to AIDS and TB; International audience; OBJECTIVE: To investigate the impact of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) upon immunological recovery and the T-cell compartment after initiation of TB and antiretroviral therapy (ART).DESIGN AND METHODS: We prospectively evaluated T-cell immunophenotypes by flow cytometry and cytokines by Luminex assays in a subset (n = 154) of highly immunosuppressed HIV-infected patients with TB from the Cambodian Early versus Late Introduction of Antiretrovirals randomized clinical trial. We compared findings from patients who developed TB-IRIS with findings from patients who did not develop TB-IRIS. Data were evaluated with mixed-effect linear regression, Kaplan-Meier estimates, and Wilcoxon rank-sum tests, and q-values were calculated to control for multiple comparisons.RESULTS: Development of TB-IRIS was associated with significantly greater pre-ART frequencies of HLA-DRCD45ROCD4, CCR5CD4, OX40CD4, and Fas effector memory CD8 T cells, and significantly elevated levels of plasma interleukin (IL)-6, IL-1β, IL-8, and IL-10, and viral load. Post-ART initiation, effector memory CD4 and Fas effector memory CD4 T-cell frequencies significantly expanded, and central memory CD4 T-cell frequencies significantly contracted in patients who experienced TB-IRIS. By week 34 post-TB treatment initiation, effector memory/central memory CD4 T-cell ratios were markedly higher in TB-IRIS versus non-TB-IRIS patients.CONCLUSIONS: A distinct pattern of pre-ART T-cell and cytokine markers appear to poise the immune response of certain patients to develop TB-IRIS. Experience of TB-IRIS is then associated with long-term remodeling of the CD4 T-cell memory compartment towards an effector memory-dominated phenotype. We speculate that these pre and post-ART TB-IRIS-associated immune parameters may contribute to superior immune control of TB/HIV co-infection and better clinical outcome.
Published: 2015

50. Fluoroquinolone resistance and Mycobacterium tuberculosis: CAP guidelines play an important role

Author: Sophie, Goyet, Erika, Vlieghe, Kruy, Lim, Johan, van Griensven, Laurence, Borand, Phe, Thong, Blandine, Rammaert, Olivier, Marcy, and Arnaud, Tarantola
Subjects: Drug Resistance, Multiple, Bacterial, Tuberculosis, Multidrug-Resistant, Humans, Mycobacterium tuberculosis, Antibiotics, Antitubercular, Fluoroquinolones
Published: 2014

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