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BackgroundHealthcare-associated infections pose a major, yet often preventable risk to patient safety. Poor hand hygiene among healthcare personnel and unsanitary hospital environments may contribute to this risk in low-income settings. We aimed to describe hand hygiene behaviour and environmental contamination by season in a rural, sub-Saharan African hospital setting.MethodsWe conducted a concurrent triangulation mixed-methods study combining three types of data at a hospital in Madarounfa, Niger. Hand hygiene observations among healthcare personnel during two seasons contributed quantitative data describing hand hygiene frequency and its variability in relation to seasonal changes in caseload. Semistructured interviews with healthcare personnel contributed qualitative data on knowledge, attitudes and barriers to hand hygiene. Biweekly environmental samples evaluated microbial contamination from October 2016 to December 2017. Triangulation identified convergences, complements and contradictions across results.ResultsHand hygiene compliance, or the proportion of actions (handrubbing or handwashing) performed out of all actions required, was low (11% during non-peak and 36% during peak caseload seasons). Interviews with healthcare personnel suggesting good general knowledge of hand hygiene contradicted the low hand hygiene compliance. However, compliance by healthcare activity was convergent with poor knowledge of precise hand hygiene steps and the motivation to prevent personal acquisition of infection identified during interviews. Contamination of environmental samples with gram-negative bacilli was high (45%), with the highest rates of contamination observed during the peak caseload season.ConclusionLow hand hygiene compliance coupled with high contamination rates of hospital environments may increase the risk of hospital-acquired infections in sub-Saharan African settings.

Background The World Health Organization recommends the use of a weight-for-height Z-score (WHZ) and/or mid-upper arm circumference (MUAC) as anthropometric criteria for the admission and discharge of young children for the community-based management of severe acute malnutrition. However, using MUAC as a single anthropometric criterion for admission and discharge in therapeutic nutritional programs may offer operational advantages to simplify admission processes at therapeutic nutritional centers and improve program coverage. Methods This pragmatic, non-randomized, intervention study compared a standard outpatient nutritional program (n = 824) for the treatment of uncomplicated severe acute malnutrition using WHZ n = 1019) using MUAC as the sole anthropometric criterion for admission (MUAC Results Compared to the standard program, the MUAC-only program discharged more children as recovered (70.1% vs. 51.6%; aOR 2.31, 95%CI 1.79–2.98) and fewer children as non-respondent or defaulters, based on respective program definitions. The risk of non-response was high in both programs. Three months post-discharge, children who were discharged after recovery in the MUAC-only program had lower WHZ and MUAC measures. Sixty-three children ineligible for the MUAC-only program but eligible for a standard program (MUAC ≥120 mm and WHZ Conclusions The results from this study share the first operational experience of using MUAC as sole anthropometric criterion for admission and discharge in Niger and overall support the consideration for MUAC-only programming: the MUAC-only model of care was associated with a higher recovery and a lower defaulter rate than the standard program with very few children found to be excluded from treatment with an admission criterion of MUAC

Background During a measles epidemic, the Ministry of Public Health (MOH) of the Democratic Republic of the Congo conducted supplementary immunization activities (2016-SIA) from August 28-September 3, 2016 throughout Maniema Province. From October 29-November 4, 2016, Medecins Sans Frontieres and the MOH conducted a reactive measles vaccination campaign (2016-RVC) targeting children six months to 14 years old in seven health areas with heavy ongoing transmission despite inclusion in the 2016-SIA, and a post-vaccination survey. We report the measles vaccine coverage (VC) and effectiveness (VE) of the 2016-SIA and VC of the 2016-RVC. Methods A cross-sectional VC cluster survey stratified by semi-urban/rural health area and age was conducted. A retrospective cohort analysis of measles reported by the parent/guardian allowed calculation of the cumulative measles incidence according to vaccination status after the 2016-SIA for an estimation of crude and adjusted VE. Results In November 2016, 1145 children (6–59 months old) in the semi-urban and 1158 in the rural areas were surveyed. Post-2016-SIA VC (documentation/declaration) was 81.6% (95%CI: 76.5–85.7) in the semi-urban and 91.0% (95%CI: 84.9–94.7) in the rural areas. The reported measles incidence in October among children less than 5 years old was 5.0% for 2016-SIA-vaccinated and 11.2% for 2016-SIA-non-vaccinated in the semi-urban area, and 0.7% for 2016-SIA-vaccinated and 4.0% for 2016-SIA-non-vaccinated in the rural area. Post-2016-SIA VE (adjusted for age, sex) was 53.9% (95%CI: 2.9–78.8) in the semi-urban and 78.7% (95%CI: 0–97.1) in the rural areas. Post 2016-RVC VC (documentation/declaration) was 99.1% (95%CI: 98.2–99.6) in the semi-urban and 98.8% (95%CI: 96.5–99.6) in the rural areas. Conclusions Although our VE estimates could be underestimated due to misclassification of measles status, the VC and VE point estimates of the 2016-SIA in the semi-urban area appear suboptimal, and in combination, could not limit the epidemic. Further research is needed on vaccination strategies adapted to urban contexts.

Many factors can contribute to low coverage of treatment for severe acute malnutrition (SAM), and a limited number of health facilities and trained personnel can constrain the number of children that receive treatment. Alternative models of care that shift the responsibility for routine clinical and anthropometric surveillance from the health facility to the household could reduce the burden of care associated with frequent facility‐based visits for both healthcare providers and caregivers. To assess the feasibility of shifting clinical surveillance to caregivers in the outpatient management of SAM, we conducted a pilot study to assess caregivers' understanding and retention of key concepts related to the surveillance of clinical danger signs and anthropometric measurement over a 28‐day period. At the time of a child's admission to nutritional treatment, a study nurse provided a short training to groups of caregivers on two topics: (a) clinical danger signs in children with SAM that warrant facility‐based care and (b) methods to measure and monitor their child's mid‐upper arm circumference. Caregiver understanding was assessed using standardized questionnaires before training, immediately after training, and 28 days after training. Knowledge of most clinical danger signs (e.g., convulsions, edema, poor appetite, respiratory distress, and lethargy) was low (0–45%) before training but increased immediately after and was retained 28 days after training. Agreement between nurse–caregiver mid‐upper arm circumference colour classifications was 77% (98/128) immediately after training and 80% after 28 days. These findings lend preliminary support to pursue further study of alternative models of care that allow for greater engagement of caregivers in the clinical and anthropometric surveillance of children with SAM.

Background In low-resource settings, the lack of mental health professionals and cross-culturally validated screening instruments complicates mental health care delivery. This is especially the case for very young children. Here, we aimed to develop and cross-culturally validate a simple and rapid tool, the PSYCa 6–36, that can be administered by non-professionals to screen for psychological difficulties among children aged six to 36 months. Methods A primary validation of the PSYCa 6–36 was conducted in Kenya (n = 319 children aged 6 to 36 months; 2014), followed by additional validations in Kenya (n = 215; 2014) Cambodia (n = 189; 2015) and Uganda (n = 182; 2016). After informed consent, trained interviewers administered the PSYCa 6–36 to caregivers participating in the study. We assessed the psychometric properties of the PSYCa 6–36 and external validity was assessed by comparing the results of the PSYCa 6–36 against a clinical global impression severity [CGIS] score rated by an independent psychologist after a structured clinical interview with each participant. Results The PSYCa 6–36 showed satisfactory psychometric properties (Cronbach’s alpha > 0.60 in Uganda and > 0.70 in Kenya and Cambodia), temporal stability (intra-class correlation coefficient [ICC] > 0.8), and inter-rater reliability (ICC from 0.6 in Uganda to 0.8 in Kenya). Psychologists identified psychological difficulties (CGIS score > 1) in 11 children (5.1%) in Kenya, 13 children (8.7%) in Cambodia and 15 (10.5%) in Uganda, with an area under the receiver operating characteristic curve of 0.65 in Uganda and 0.80 in Kenya and Cambodia. Conclusions The PSYCa 6–36 allowed for rapid screening of psychological difficulties among children aged 6 to 36 months among the populations studied. Use of the tool also increased awareness of children’s psychological difficulties and the importance of early recognition to prevent long-term consequences. The PSYCa 6–36 would benefit from further use and validation studies in popula`tions with higher prevalence of psychological difficulties. Electronic supplementary material The online version of this article (10.1186/s12887-019-1461-3) contains supplementary material, which is available to authorized users.

Oral cholera vaccine (OCV) has increasingly been used as an outbreak control measure, but vaccine shortages limit its application. A two-dose OCV campaign targeting residents aged over 1 year was launched in three rural Communes of Southern Haiti during an outbreak following Hurricane Matthew in October 2016. Door-to-door and fixed-site strategies were employed and mobile teams delivered vaccines to hard-to-reach communities. This was the first campaign to use the recently pre-qualified OCV, Euvichol. The study objective was to estimate post-campaign vaccination coverage in order to evaluate the campaign and guide future outbreak control strategies. We conducted a cluster survey with sampling based on random GPS points. We identified clusters of five households and included all members eligible for vaccination. Local residents collected data through face-to-face interviews. Coverage was estimated, accounting for the clustered sampling, and 95% confidence intervals calculated. 435 clusters, 2,100 households and 9,086 people were included (99% response rate). Across the three communes respectively, coverage by recall was: 80.7% (95% CI:76.8–84.1), 82.6% (78.1–86.4), and 82.3% (79.0–85.2) for two doses and 94.2% (90.8–96.4), 91.8% (87–94.9), and 93.8% (90.8–95.9) for at least one dose. Coverage varied by less than 9% across age groups and was similar among males and females. Participants obtained vaccines from door-to-door vaccinators (53%) and fixed sites (47%). Most participants heard about the campaign through community ‘criers’ (58%). Despite hard-to-reach communities, high coverage was achieved in all areas through combining different vaccine delivery strategies and extensive community mobilisation. Emergency OCV campaigns are a viable option for outbreak control and where possible multiple strategies should be used in combination. Euvichol will help alleviate the OCV shortage but effectiveness studies in outbreaks should be done., Author summary After Hurricane Matthew hit Southern Haiti on October 4, 2016, there was an outbreak of Cholera. The Government launched a campaign to vaccinate residents using an oral vaccine, which has been proven to protect people against the disease. MSF supported the campaign in three rural areas, offering the vaccine in local clinics and going from door to door. We didn’t know how many people were living there at the time so we couldn’t say for sure if we had vaccinated enough people. To find out how many people were vaccinated we did a survey, choosing households at random and asking them if and where they received the vaccine. This showed that on average around 90% of people were vaccinated, which is a very high proportion. We can take encouragement from this that mass vaccination campaigns like this can work well, even in rural settings. Our survey showed that about half of people got their vaccine from a clinic and the other half from door-to-door vaccinators, so it’s probably important to use both approaches. Most people heard about the campaign through members of the local community called ‘criers’. This shows how important it is to engage with the local community during a vaccination campaign.

Background Quantification of human interactions relevant to infectious disease transmission through social contact is central to predict disease dynamics, yet data from low-resource settings remain scarce. Methods We undertook a social contact survey in rural Uganda, whereby participants were asked to recall details about the frequency, type, and socio-demographic characteristics of any conversational encounter that lasted for ≥5 min (henceforth defined as ‘contacts’) during the previous day. An estimate of the number of ‘casual contacts’ (i.e.

Infections of the central nervous system (CNS) are severe conditions, leading to neurological sequelae or death. Knowledge of the causative agents is essential to develop guidelines for case management in resource-limited settings. Between August 2009 and October 2012, we conducted a prospective descriptive study of the aetiology of suspected CNS infections in children two months to 12 years old, with fever and at least one sign of CNS involvement in Mbarara Hospital, Uganda. Children were clinically evaluated on admission and discharge, and followed-up for 6 months for neurological sequelae. Pathogens were identified from cerebrospinal fluid (CSF) and blood using microbiological and molecular methods. We enrolled 459 children. Plasmodium falciparum (36.2%) and bacteria in CSF (13.3%) or blood (3.3%) were the most detected pathogens. Viruses were found in 27 (5.9%) children. No pathogen was isolated in 207 (45.1%) children. Patterns varied by age and HIV status. Eighty-three (18.1%) children died during hospitalisation, and 23 (5.0%) during follow-up. Forty-one (13.5%) children had neurological sequelae at the last visit. While malaria remains the main aetiology in children with suspected CNS infections, no pathogen was isolated in many children. The high mortality and high rate of neurological sequelae highlight the need for efficient diagnosis.

Background: Information on Streptococcus pneumoniae nasopharyngeal (NP) carriage before the pneumococcal conjugate vaccine (PCV) introduction is essential to monitor impact. The 10-valent PCV (PCV10) was officially introduced throughout Ugandan national childhood immunization programs in 2013 and rolled-out countrywide during 2014. We aimed to measure the age-specific Streptococcus pneumoniae carriage and serotype distribution across all population age groups in the pre-PCV10 era in South Western Uganda. Methods: We conducted a two-stage cluster, age-stratified, cross-sectional community-based study in Sheema North sub-district between January and March 2014. One NP swab was collected and analyzed for each participant in accordance with World Health Organization guidelines. Results: NP carriage of any pneumococcal serotype was higher among children < 2years old (77%; n=387) than among participants aged ≥15years (8.5%; n=325) (chi 2 p < 0.001).Of the 623 positive cultures, we identified 49 serotypes among 610 (97.9%) isolates; thirteen (2.1%) isolates were non-typeable. Among < 2. years old, serotypes 6A, 6B, 14, 15B, 19F and 23F accounted for half of all carriers. Carriage prevalence with PCV10 serotypes was 29.4% among individuals aged < 2. years (n = 387), 23.4% in children aged 2-4. years (n = 217), 11.4% in 5-14. years (n = 417), and 0.4% among individuals ≥15. years of age (n = 325). The proportion of carried pneumococci serotypes contained in PCV10 was 38.1% (n = 291), 32.8% (n = 154), 29.4% (n = 156), and 4.4% (n = 22) among carriers aged < 2. years, 2-4. years, 5-14. years and ≥15. years, respectively. Discussion: In Sheema district, the proportion of PCV10 serotypes was low ( < 40%), across all age groups, especially among individuals aged 15. years or older ( < 5%). PCV10 introduction is likely to impact transmission among children and to older individuals, but less likely to substantially modify pneumococcal NP ecology among individuals aged 15. years or older.

Background: Community-based management of severe acute malnutrition (SAM) has been shown to be safe and cost-effective, but program coverage remains low. Treatment models that maintain high levels of clinical effectiveness but allow for increased coverage are still needed. A reduced schedule of follow-up, in which children receive clinical follow-up and therapeutic foods on a monthly rather than weekly basis, may be one alternative.Objective: We aimed to describe the safety and feasibility of a monthly distribution of ready-to-use therapeutic food (RUTF) in the treatment of uncomplicated SAM, in terms of clinical response to treatment and household RUTF use.Design: We conducted a nonrandomized pilot intervention study in which 115 children eligible for outpatient treatment of SAM were provided a monthly ration of RUTF. Anthropometric measurements were taken weekly for 4 wk to monitor treatment response. Unannounced household spot checks were conducted over 4 wk to assess household use of RUTF and storage practices.Results: Adequate weight and midupper arm circumference (MUAC) gain were found throughout the 4-wk follow-up period. Observed mean ± SD weight gain from admission was 9.8 ± 6.8 g · kg-1 · d-1 in week 1 and 4.2 ± 2.1 g · kg-1 · d-1 by week 4. Unplanned household spot checks found an average surplus of RUTF sachets compared with the number expected based on the date of distribution and recommended dosing throughout the 4 wk of follow-up. The frequency at which more than the recommended dose was used (i.e., deviance of >2 sachets between available and expected stocks) was 4% and 22% of households visited in week 1 and week 4, respectively.Conclusion: Adequate treatment response and RUTF use in the outpatient treatment of SAM was maintained over 4 wk of follow-up with a monthly schedule of RUTF distribution. This study was registered at clinicaltrials.gov as NCT02994212.

Acute central nervous system (CNS) infections in children in sub-Saharan Africa are often fatal. Potential contributors include late presentation, limited diagnostic capacity and inadequate treatment. A more nuanced understanding of treatment practices with a goal of optimizing such practices is critical to prevent avoidable case fatality. We describe empiric antimicrobial treatment, antibiotic resistance and treatment adequacy in a prospective cohort of 459 children aged two months to 12 years hospitalised for suspected acute CNS infections in Mbarara, Uganda, from 2009 to 2012. Among these 459 children, 155 had a laboratory-confirmed diagnosis of malaria (case-fatality rate [CFR] 14%), 58 had bacterial infections (CFR 24%) and 6 children had mixed malaria and bacterial infections (CFR 17%). Overall case fatality was 18.1% (n = 83). Of 219 children with laboratory-confirmed malaria and/or bacterial infections, 182 (83.1%) received an adequate antimalarial and/or antibiotic on the day of admission and 211 (96.3%) within 48 hours of admission. The proportion of those receiving adequate treatment was similar among survivors and non-survivors. All bacterial isolates were sensitive to ceftriaxone except one Escherichia coli isolate with extended-spectrum beta-lactamase (ESBL). The observed high mortality was not a result of inadequate initial antimicrobial treatment at the hospital. The epidemiology of CNS infection in this setting justifies empirical use of a third-generation cephalosporin, however antibiotic resistance should be monitored closely.

Background Improving knowledge on local determinants of visceral leishmaniasis (VL) is crucial to guide the development of relevant control strategies. This study aimed to identify individual and household level determinants of primary VL in 24 highly endemic villages of Tabarak Allah hospital’s catchment area, Gedaref State, Sudan. Methods From September 2012 to July 2013, in an unmatched case-control design, 198 patients with primary VL were compared to 801 controls free of VL symptoms and with a negative VL rapid test. Using random spatial sampling, controls were selected with a distribution of age, sex and village of residence proportionate to the distribution of the target population. Data were collected using a structured questionnaire. Results Children and men were at higher risk of VL. Reporting VL patient(s) in the household in the previous year was the strongest VL risk factor. In a multivariate analysis, VL risk increased with household size, sleep location (outside the yard, not in the farm), evening outdoor activities in the rainy season (playing, watching TV, radio listening), use of ground nut oil as animal repellent and of smoke of Acacia seyal as indoor repellent, presence of dogs in the yard at night, Acacia nilotica in the yard’s immediate surroundings and of a forest at eye range. VL risk appeared to decrease with the use of drinking water sources other than the village water tank, a buffer distance from the adjacent house yard, and with the presence of animals other than dogs in the yard at night. In contrast with previous studies, housing factors, mosquito-net use, black cotton soil, ethnicity, socioeconomic index, presence of Balanites aegyptica and Azadirachta indica in the yard were not independent VL determinants. Discussion and conclusion Although these results do not provide evidence of causality, they provide useful suggestions for guiding further intervention studies on VL preventive measures., Author Summary Visceral leishmaniasis (VL), a fatal disease without treatment, is caused by a parasite (Leishmania) transmitted to humans through sandflies. Its epidemiology and the vectors involved in its transmission differ importantly between endemic zones. Preventive measures aim at reducing the parasite reservoirs and at limiting human exposure to sandflies. In Sudan, there is a lack of knowledge on VL risk and protective factors, limiting the possibility of development of control strategies. We conducted a study in a VL endemic area, Gedaref State (Sudan), to identify individual and household level determinants of clinical VL. We compared several characteristics of VL patients and inhabitants free of VL. We found that having a household member sick with VL in the previous year was the strongest VL risk factor. VL risk also seemed to be influenced by the household size, sleep location, evening outdoor activities, use of some repellents, and proximity to dogs at night. VL risk also appeared to decrease with a buffer distance between adjacent house yard and with the proximity to animals other than dogs at night. Our findings provide useful suggestions for guiding further intervention studies on VL preventive measures.

Background: Difficulty to obtain sputum in children complicates diagnosis of intrathoracic tuberculosis (TB). The intragastric string test (ST) used for retrieval of enteric pathogens might be an alternative specimen collection method but requires further evaluation of its utility in TB diagnosis. We conducted a cross-sectional study comparing the TB detection yield and the tolerability of ST and sputum induction (SI) in children. Methods: Two ST and SI procedures were performed in children (3-14 years of age) who were clinically suspected of having TB. The string was removed after a 2-hour gastric downtime, and SI was done after a maximum of 20 minutes nebulization with 5% saline solution. LED-fluorescence microscopy and mycobacterial cultures were performed on all specimens, and XpertMTB/RIF assay was performed on stored specimen sediments. Tolerability questionnaires were administered to parents of children. Results: Of 137 included children (median age: 8.1 years; 33.3% with HIV infection), 14 (10.2%) were diagnosed with TB, 10 (71.4%) by ST and 12 (85.7%) by SI. Among 105 children with both ST and SI performed, 5 (4.8%) versus 4 (3.8%) were smear positive using ST and SI, respectively (McNemar P = 1.00). Nine (8.6%) in each group had positive cultures (P = 1.00). Of 64 children tested with XpertMTB/RIF, 3 (4.7%) of the ST group versus 4 (6.3%) of the SI group were TB positive (P = 1.00). No adverse serious events were reported. ST could not be performed in 22 of 137 (16.1%) children because they were unable to swallow the capsule. Conclusions: TB detection yield was comparable between ST and SI. The tolerability of ST in young children might be improved by the reduction of the size of the capsule.

Risk factors for Buruli ulcer (BU) are poorly understood. We conducted a case-control study in southern Benin to investigate the association between haemoglobin variants S or C and BU, and particularly the association between haemoglobinopathies HbSS/SC and BU osteomyelitis. We compared the haemoglobin genotype of 179 patients with BU and 44 with BU osteomyelitis to that of 242 community controls. We found no evidence of an increased risk of BU according to the presence of haemoglobin variants S and/or C [odds ratio adjusted for sex, age, region of residence and ethnicity: 1.24 (95% CI: 0.80-1.93), P = 0.34]. Haemoglobin variants S and C are unlikely to play a role in the BU burden. However, haemoglobinopathies HbSS/SC were more frequent among BU osteomyelitis patients than among controls (6.8% vs. 1.0%, Fisher's exact P-value = 0.045), which may suggest that those disorders facilitate growth of Mycobacterium ulcerans in the bone matrix.

BCG remains the only possible prophylactic intervention against Buruli ulcer (BU). Estimating its public health impact on BU control is an important issue. We conducted a case-control study to investigate the vaccine effectiveness of routine BCG vaccine against BU in southern Benin. From August 2002 to August 2003, BCG vaccination status was obtained for 279 clinically diagnosed BU cases and 988 age- and sex-matched neighborhood controls. BCG coverage, which was estimated by the presence of a scar or a vaccination record, was 64.5% in cases and 67.2% in controls. There was no evidence of a protective effect of routine BCG vaccination against BU in southern Benin (vaccine effectiveness adjusted for socioeconomic status = 12%, 95% confidence interval = -24% to 37%).

The skin disease Buruli ulcer, caused by Mycobacterium ulcerans, is the third most common mycobacterial disease after tuberculosis and leprosy and mainly affects remote rural African communities. Although the disease is known to be linked to contaminated water, the mode of transmission is not yet understood, which makes it difficult to propose control interventions. The disease is usually detected in its later stages, when it has caused substantial damage and disability. Surgery remains the treatment of choice. Although easy and effective in the early stages of the disease, treatment requires extended excisions and long hospitalisation for the advanced forms of the disease. Currently, no antibiotic treatment has proven effective for all forms of M ulcerans infection and research into a new vaccine is urgently needed. While the scientific community works on developing non-invasive and rapid diagnostic tools, the governments of endemic countries should implement active case finding and health education strategies in their affected communities to detect the disease in its early stages. We review the diagnosis, treatment, and control of Buruli ulcer and list priorities for research and development.

Background Typhoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare. Methods A typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff's spatial scan statistic. Principal Findings We analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff's spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic. Conclusions This study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range.

Background: Intensified efforts are urgently needed to contain and eliminate artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion. Medecins Sans Frontieres plans to support the Ministry of Health in eliminating P. falciparum in an area with artemisinin resistance in the north-east of Cambodia. As a first step, the prevalence of Plasmodium spp. and the presence of mutations associated with artemisinin resistance were evaluated in two districts of Preah Vihear Province. Methods: A cross-sectional population-based study using a two-stage cluster sampling was conducted in the rural districts of Chhaeb and Chey Saen, from September to October 2013. In each district, 30 clusters of 10 households were randomly selected. In total, blood samples were collected for 1,275 participants in Chhaeb and 1,224 in Chey Saen. Prevalence of Plasmodium spp. was assessed by PCR on dried blood spots. Plasmodium falciparum positive samples were screened for mutations in the K13-propeller domain gene (PF3D7_1343700). Result: The prevalence of Plasmodium spp. was estimated at 1.49% (95% CI 0.71–3.11%) in Chhaeb and 2.61% (95% CI 1.45–4.66%) in Chey Saen. Twenty-seven samples were positive for P. falciparum, giving a prevalence of 0.16% (95% CI 0.04–0.65) in Chhaeb and 2.04% (95% CI 1.04–3.99%) in Chey Saen. Only 4.0% of the participants testing positive presented with fever or history of fever. K13-propeller domain mutant type alleles (C580Y and Y493H) were found, only in Chey Saen district, in seven out of 11 P. falciparum positive samples with enough genetic material to allow testing. Conclusion: The overall prevalence of P. falciparum was low in both districts but parasites presenting mutations in the K13-propeller domain gene, strongly associated with artemisinin-resistance, are circulating in Chey Saen.The prevalence might be underestimated because of the absentees – mainly forest workers - and the workers of private companies who were not included in the study. These results confirm the need to urgently develop and implement targeted interventions to contain and eliminate P. falciparum malaria in this district before it spreads to other areas.

OBJECTIVE: To investigate the possible association between the body burden of dioxin-like compounds and endometriotic disease. DESIGN: Case-control study. SETTING: Gynecology ward in a university hospital. PATIENT(S): Seventy-one women with peritoneal endometriosis (n = 25) or deep endometriotic (adenomyotic) nodules (n = 25) and controls (n = 21). INTERVENTION(S): Collection of 200 mL of blood (fasted) and face-to-face interview. MAIN OUTCOME MEASURE(S): Assessment of dioxin (PCDD), furan (PCDF), and dioxin-like PCB serum concentrations (picograms toxic equivalent [TEQ]/g lipids). RESULT(S): Age and body mass index were traced by linear multiple regression as determinants of total TEQ levels. After standardization for these variables (30 years and 22.5 kg/m2), the mean TEQ levels were 24.21 (controls), 30.62 (peritoneal endometriosis), and 37.60 (deep endometriotic [adenomyotic] nodules) pg TEQ/g lipids. Logistic regression analysis indicated a significantly increased risk of deep endometriotic (adenomyotic) nodules (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.4-7.6) for an increment of 10 pg in total TEQ levels/g lipids. An increased risk was also found for peritoneal endometriosis (OR, 1.9; 95% CI, 0.9-3.8) for total TEQ levels and for dioxins alone (OR, 3.2; 95% CI, 1.0-9.9). CONCLUSION(S): The results provide the first epidemiological evidence of an association between increased PCDD/PCDF and PCB body burden and endometriosis.

OBJECTIVE: A lack of global cardiovascular (CV) risk approach is often observed in the clinical practice. Having conceived a clinical strategy aimed at helping general practitioners (GPs) to assess and manage global CV risk in the daily practice, we wanted to evaluate the impact of a training promoting this strategy. METHODS: Randomised controlled trial involving GPs registered in a continual medical education (CME) group. The intervention and control arms included 7 (123 GPs) and 13 (220 GPs) groups, respectively. The intervention was a training in CV prevention provided during a CME meeting. GPs answered a questionnaire four months after the training. The main outcome was the use of a global CV risk assessment tool. Secondary outcomes were the GPs' awareness of the CV diseases burden, knowledge of the CV risk factors, and CV therapeutic attitudes. RESULTS: More trained GPs (76% vs. 52%) used a global CV risk assessment tool (p = 0.003). Significant differences were also observed for secondary outcomes: (a) awareness of CV diseases burden: more trained GPs were aware of the lethality from myocardial infarction (37% vs. 21%, p = 0.047) and considered it as the main cause of sudden death in adults (78% vs. 59%, p = 0.018); (b) knowledge of risk factors: more trained GPs considered familial CV history (89% vs. 73%, p = 0.021) and HDL-cholesterol (82% vs. 62%, p = 0.013) as important CV risk factors; (c) therapeutic attitudes: fewer trained GPs used to prescribe a lipid-lowering drug based on a total cholesterol value without considering the other risk factors (44% vs. 65%, p = 0.013). CONCLUSIONS: The global CV risk approach in the general practice was favourably influenced by this training provided during a CME meeting. The impact of the training on patients' outcomes should be addressed in a prospective trial.

OBJECTIVES: To investigate the virological outcome of chronic hepatitis B (CH-B) in children who received interferon alpha (IFN) compared with no treatment. METHODS: Seventy-four children with CH-B (median age, 6.1 years; 44 boys) selected from a cohort of 158 cases were included and divided into two groups: IFN-treated (n = 37) and control (n = 37). The controls were matched with the treated children by baseline alanine aminotransferase (ALT) levels, sex and age. The Kaplan-Meier method was performed to estimate the time to clearance of hepatitis B e antigen (HbeAg) and hepatitis B surface antigen (HbsAg). RESULTS: Mean duration of follow-up was comparable in two groups (5.2 +/- 3.8 years in treatment group versus 5.2 +/- 3.7 years in control group, NS). HBeAg and HBsAg loss occurred in 20 (54.1%) and three treated children versus 13 (35.1%) and one untreated children (NS), respectively. The 7-year cumulative HBeAg and HBsAg clearance rates were 47.5% and 8.9% after the first visit in the treatment group versus 33.5% and 4.0% in untreated children (NS), respectively. Elevated baseline ALT (two times upper limit of normal) had a significant effect on the long-term cumulative rate of HBeAg seroconversion in treated patients (P = 0.01) but not in the untreated group. CONCLUSIONS: These findings show that the overall long-term virological outcome does not differ significantly between IFN-treated and untreated children but that a significant benefit of treatment on the long term rate of HBeAg seroconversion is obtained in children with higher baseline ALT levels.

Environmental chemicals with oestrogen-like activity are suspected aetiological factors of endometriosis. In animal experiments, cadmium was recently shown to possess oestrogen-like properties. In the frame of a case-control study designed to investigate environmental risk factors for endometriosis, we compared cadmium urinary excretion (CdU) and blood concentration in 59 patients with peritoneal endometriosis, deep endometriotic (adenomyotic) nodules of the recto-vaginal septum and controls. After standardisation for age (30 years) and smoking status, the mean levels of cadmium in urine were (geometric mean [geometric S.D.]) 0.25 [1.50], 0.29 [1.76] and 0.26 [1.46] microg/g creatinine, respectively. Cadmium concentrations in blood did not differ among the three groups. These data, therefore, do not support a role for cadmium in the onset or the growth of endometriosis or deep endometriotic (adenomyotic) nodules of the recto-vaginal septum.

Background: In 2009, a large meningitis A epidemic affected a broad region of northern Nigeria and southern Niger, resulting in more than 75 000 cases and 4000 deaths. In collaboration with state and federal agencies, Medecins Sans Frontieres (MSF) intervened with a large-scale vaccination campaign using polysaccharide vaccine. Here the authors analyze the impact (cases averted) of the vaccination response as a function of the timing and coverage achieved. Methods: Phenomenological epidemic models were fitted to replicate meningitis surveillance data from the Nigerian Ministry of Health/WHO surveillance system and from reinforced surveillance conducted by MSF in both vaccinated and unvaccinated areas using a dynamic, state-space framework to account for under-report- ing of cases. Results: The overall impact of the vaccination campaigns (reduction in meningitis cases) in Katsina State, northern Nigeria, ranged from 4% to 12%. At the local level, vaccination reduced cases by as much as 50% when campaigns were conducted early in the epidemic. Conclusions: Reactive vaccination with polysaccharide vaccine during meningitis outbreaks can significantly reduce the case burden when conducted early and comprehensively. Introduction of the conjugate MenAfriVac vaccine has reduced rates of disease caused by serogroup A Neisseria meningitidis in the region. Despite this, reactive campaigns with polysaccharide vaccine remain a necessary and important tool for meningitis outbreak response.

The sum of bulk polychlorobiphenyl levels was significantly higher in women with rectovaginal adenomyosis than in women with endometriosis and controls.

Background Since December 2009, Médecins Sans Frontières has diagnosed and treated patients with visceral leishmaniasis (VL) in Tabarak Allah Hospital, eastern Gedaref State, one of the main endemic foci of VL in Sudan. A survey was conducted to estimate the VL incidence in villages around Tabarak Allah. Methods Between the 5th of May and the 17th of June 2011, we conducted an exhaustive door-to-door survey in 45 villages of Al-Gureisha locality. Deaths were investigated by verbal autopsies. All individuals with (i) fever of at least two weeks, (ii) VL diagnosed and treated in the previous year, and (iii) clinical suspicion of post-kala-azar dermal leishmaniasis (PKDL) were referred to medical teams for case ascertainment. A new case of VL was a clinical suspect with a positive rk39 rapid test or direct agglutination test (DAT). Results In the 45 villages screened, 17,702 households were interviewed, for a population of 94,369 inhabitants. The crude mortality rate over the mean recall period of 409 days was 0.13/10'000 people per day. VL was a possible or probable cause for 19% of all deaths. The VL-specific mortality rate was estimated at 0.9/1000 per year. The medical teams examined 551 individuals referred for a history of fever of at least two weeks. Out of these, 16 were diagnosed with primary VL. The overall incidence of VL over the past year was 7.0/1000 persons per year, or 7.9/1000 per year when deaths possibly or probably due to VL were included. Overall, 12.5% (11,943/95,609) of the population reported a past VL treatment episode. Discussion and Conclusion VL represents a significant health burden in eastern Gedaref State. Active VL case detection had a very low yield in this specific setting with adequate access to care and may not be the priority intervention to enhance control in similar contexts., Author Summary Visceral leishmaniasis (VL) is a life-threatening parasitic disease, transmitted by a sandfly. A survey was conducted to estimate the VL incidence in 45 villages located in the eastern part of Gedaref State, the main endemic focus of VL in Sudan. Between the 5th of May and the 17th of June 2011, we interviewed 17,702 households for a population of 94,369. Sixteen individuals were diagnosed with primary VL through active case-detection, and 725 reported VL treatment over the past year. The overall incidence rate of VL over the past year was 7.0/1000 persons per year. The crude mortality rate over the mean recall period of 409 days was 0.13/10'000 persons per day. VL was a possible or probable cause for 19% of all deaths. Taking also into account the VL-specific mortality of 0.9/1000 per year, the incidence was estimated at 7.9/1000 per year. Overall, 12.5% of the population reported having been treated for VL in the past. VL is a major public health issue in Gedaref. Active VL case detection had a very low yield in a context of adequate access to care. Such strategy seems redundant if patients already have access to care.

We investigated the association between Buruli ulcer and HIV by comparing the HIV-1/2 seroprevalence in a series of 426 Buruli ulcer patients and a sample of 613 residents of southern Benin. The overall HIV prevalence was 2.6% (11/426) among patients and 0.3% among controls (2/613), giving an odds ratio for the association between HIV and Buruli ulcer of 8.1 (95% confidence interval = 1.8-75; P = 0.003).

We conducted a case-control study to investigate the association between Buruli ulcer (BU) and environmental- and health-related behaviors in southern Benin. Hospital BU cases (N = 324) and sex- and age-matched neighborhood controls (N = 1,173) answered a questionnaire. Regular use of soap for washing, treating injuries with soap or antibiotic powder, and frequent contact with flowing water appeared protective against BU.

Peritoneal endometriosis (PE) and deep endometriotic nodules (DEN) are gynecological diseases recently shown to be associated with elevated serum concentrations of organochlorines. The objective of the present study was to compare risk factors associated with both forms of the disease, with a particular attention to potential sources of organochlorine exposure. This matched case-control study with prospective recruitment included 88 triads (PE-DEN-control). All women were face-to-face interviewed with a standardized questionnaire, and serum dioxin and polychlorinated biphenyl measurements were available for 58 of them. Alcohol consumption (odds ratio (OR): 5.82 [confidence interval at 95% (95%CI) 1.20-28.3]) in DEN and low physical activity at work for DEN (OR: 4.58 [95%CI 1.80-11.62]) and PE (OR: 5.61 [95%CI 1.90-16.60]) were traced as significant risk factors. Organochlorine-related factors (use of tampons, occupational or environmental exposure) were not related to the disease. The current consumption of foodstuffs that were more likely to contribute to organochlorine body burden did not differ among the groups. Only some of these fatty foodstuffs (marine fish, pig meat) were traced by multiple regression analysis as significant determinants of organochlorine body burden, explaining only a small fraction (20%) of the interindividual variation of organochlorine body burden. We conclude that PE and DEN share similar patterns of risk or protective factors.

Objectives: Cadmium (Cd) and lead (Pb) have been demonstrated to exert endocrine disrupting activities. Their possible role in endometriosis, an oestrogen-dependent disease, is unknown. Methods: We compared cadmium urinary excretion (CdU) and blood concentration of cadmium (CdB) and lead (PbB) in 119 patients with peritoneal endometriosis and/or deep endometriotic (adenomyotic) nodules of the rectovaginal septum and 25 controls. Results: The mean levels of cadmium in urine and blood did not differ among the groups. Women suffering from endometriotic diseases showed lower levels of PbB than controls. Conclusions: These data do not support a role for cadmium in the onset or the growth of endometriotic diseases but suggest a possible relationship with lead.

OBJECTIVE: In spite of a wide diffusion of the European guidelines for prevention of cardiovascular (CV) diseases, failures in both primary and secondary CV prevention are currently acknowledged. We wanted to uncover obstacles to CV prevention related to the general practitioner's (GP) knowledge and attitudes. METHODS AND RESULTS: A postal questionnaire was sent to a random sample of GPs from two Belgian provinces. 282 GPs (32%) answered the questionnaire. The proportion of adequate answers was calculated for each item. The main obstacles related to three domains. Regarding awareness of CV burden, 83% of the GPs underestimated the lethality of myocardial infarction and 41% underestimated the prevalence of high CV risk in the adult population. Regarding CV risk assessment, 80% thought that total cholesterol (TC) adequately reflected the individual CV risk; only 55% systematically registered the patient's CV risk factors in the medical record. A tool for global CV risk assessment was never used by 53% of the GPs. Regarding CV therapeutic attitudes, 66% systematically prescribed a lipid-lowering drug to patients with high TC while 62% did not take into account the evidence-based therapeutic targets in type 2 diabetic patients. CONCLUSIONS: This survey showed that these GPs underestimated the CV burden, lacked a systematic approach to global risk assessment and used to focus on cholesterol treatment rather than on global CV risk management.

Background Estimation of vaccination coverage at the local level is essential to identify communities that may require additional support. Cluster surveys can be used in resource-poor settings, when population figures are inaccurate. To be feasible, cluster samples need to be small, without losing robustness of results. The clustered LQAS (CLQAS) approach has been proposed as an alternative, as smaller sample sizes are required. Methods We explored (i) the efficiency of cluster surveys of decreasing sample size through bootstrapping analysis and (ii) the performance of CLQAS under three alternative sampling plans to classify local VC, using data from a survey carried out in Mali after mass vaccination against meningococcal meningitis group A. Results VC estimates provided by a 10 × 15 cluster survey design were reasonably robust. We used them to classify health areas in three categories and guide mop-up activities: i) health areas not requiring supplemental activities; ii) health areas requiring additional vaccination; iii) health areas requiring further evaluation. As sample size decreased (from 10 × 15 to 10 × 3), standard error of VC and ICC estimates were increasingly unstable. Results of CLQAS simulations were not accurate for most health areas, with an overall risk of misclassification greater than 0.25 in one health area out of three. It was greater than 0.50 in one health area out of two under two of the three sampling plans. Conclusions Small sample cluster surveys (10 × 15) are acceptably robust for classification of VC at local level. We do not recommend the CLQAS method as currently formulated for evaluating vaccination programmes.

Background Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Medecins sans Frontieres introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools. Methods We conducted a cross-sectional survey amongst a series of new TB patients receiving 6 months of standard TB chemotherapy with FDC under SAT. Adherence was assessed at home with urine testing for Isoniazid (INH), pill count, interviewer-administered questionnaire and visual analogue scale (VAS). Results In November 2008 and in June 2009, 212 of 279 eligible patients were assessed for adherence. Overall, 95.2% [95%CI: 91.3–97.7] of the patients reported not having missed a tablet in the last 4 days. On the VAS, complete adherence was estimated at 92.5% [95%CI: 88.0–95.6]. INH urine test was positive for 97.6% [95%CI: 94.6–99.2] of the patients. Pill count could be assessed among only 70% of the interviewed patients. Among them, it was complete for 82.3% [95%CI: 75.1–88.1]. Among the 212 surveyed patients, 193 (91.0%) were successfully treated (cured or treatment completed). The data suggest a fair agreement between the questionnaire and the INH urine test (k = 0.43) and between the questionnaire and the VAS (k = 0.40). Agreement was poor between the other adherence tools. Conclusion These results suggest that SAT, together with the FDC, allows achieving appropriate adherence to antituberculosis treatment in a high TB and HIV burden area. The use of a combination of a VAS and a questionnaire can be an adequate approach to monitor adherence to TB treatment in routine program conditions.

Background Access to laboratory diagnosis can be a challenge for individuals suspected of Buruli Ulcer (BU). Our objective was to develop a clinical score to assist clinicians working in resource-limited settings for BU diagnosis. Methododology/Principal Findings Between 2011 and 2013, individuals presenting at Akonolinga District Hospital, Cameroon, were enrolled consecutively. Clinical data were collected prospectively. Based on a latent class model using laboratory test results (ZN, PCR, culture), patients were categorized into high, or low BU likelihood. Variables associated with a high BU likelihood in a multivariate logistic model were included in the Buruli score. Score cut-offs were chosen based on calculated predictive values. Of 325 patients with an ulcerative lesion, 51 (15.7%) had a high BU likelihood. The variables identified for the Buruli score were: characteristic smell (+3 points), yellow color (+2), female gender (+2), undermining (+1), green color (+1), lesion hyposensitivity (+1), pain at rest (-1), size >5cm (-1), locoregional adenopathy (-2), age above 20 up to 40 years (-3), or above 40 (-5). This score had AUC of 0.86 (95%CI 0.82–0.89), indicating good discrimination between infected and non-infected individuals. The cut-off to reasonably exclude BU was set at scores, Author Summary In most Buruli ulcer (BU) endemic areas, laboratory diagnosis is hard to access and comes at a high cost. Clinicians are in need of new tools to assist them in identifying which patients truly require additional work-up and which can be treated directly. We analyzed the clinical data of all patients with ulcerative skin lesions that presented to Akonolinga District Hospital in Cameroon and identified which parameters were associated with BU diagnosis. We attributed a certain number of points to each parameter to build a “Buruli score”. Based on score results, clinicians can be advised either to directly treat BU (score ≥4), to look for another diagnosis (score