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BackgroundIn low- and middle-income countries, the prevalence of antimicrobial resistance (AMR) is increasing. To control AMR, WHO recommends monitoring antibiotic use, in particular Watch antibiotics. These are critically important antibiotics, with restricted use because at risk of becoming ineffective due to increasing AMR. We investigated pre-hospital antibiotic use in rural Burkina Faso.MethodsDuring 2016–2017, we collected data from patients aged > 3 months presenting with severe acute fever to the rural hospital of Nanoro Health District, Burkina Faso, including antibiotic use in the two weeks prior to consultation or hospitalization. We analysed reported antibiotic use by applying the WHO Access, Watch, Reserve classification.ResultsOf 920 febrile participants (63.0% ≤ 14 years), pre-hospital antibiotic use was reported by 363 (39.5%). Among these 363, microbiological diagnoses were available for 275 (75.8%) patients, of whom 162 (58.9%) were non-bacterial infections. Use of more than one antibiotic was reported by 58/363 (16.0%) participants. Of 491 self-referred patients who did not previously visit a primary health care center, 131 (26.7%) reported antibiotic use. Of 424 antibiotics reported, 265 (62.5%) were Access and 159 (37.5%) Watch antibiotics. Watch antibiotic use was more frequent among patients > 14 year olds (51.1%) compared to those 0–14 year old (30.7%,p p = 0.004). Most frequently reported Watch antibiotics were ceftriaxone (114, 71.7%) and ciprofloxacin (32, 20.1%).ConclusionThe reported frequent use of Watch group antibiotics among febrile patients prior to presentation to the hospital in rural Burkina Faso highlights the need to develop targeted interventions to improve antibiotic use in community settings as part of strengthening antibiotic stewardship in low- and middle-income countries. This should include facilitating referral, access to qualified prescribers and diagnostic tools in rural primary health care centers.Trial registrationClinicalTrials.gov identifier: NCT02669823. Registration date was February 1, 2016.

Background Nasopharyngeal colonisation with clinically relevant bacterial pathogens is a risk factor for severe infections, such as pneumonia and bacteraemia. In this study, we investigated the determinants of nasopharyngeal carriage in febrile patients in rural Burkina Faso. Methods From March 2016 to June 2017, we recruited 924 paediatric and adult patients presenting with fever, hypothermia or suspicion of severe infection to the Centre Medical avec Antenne Chirurgicale Saint Camille de Nanoro, Burkina Faso. We recorded a broad range of clinical data, collected nasopharyngeal swabs and tested them for the presence of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Klebsiella pneumoniae by quantitative polymerase chain reaction. Using logistic regression, we investigated the determinants of carriage and aimed to find correlations with clinical outcome. Results Nasopharyngeal colonisation with S. pneumoniae, H. influenzae and M. catarrhalis was highly prevalent and strongly dependent on age and season. Females were less likely to be colonised with S. pneumoniae (OR 0.71, p = 0.022, 95% CI 0.53–0.95) and M. catarrhalis (OR 0.73, p = 0.044, 95% CI 0.54–0.99) than males. Colonisation rates were highest in the age groups K. pneumoniae prevalence was low and not significantly correlated with age or season. For S. pneumoniae and H. influenzae, we found a positive association between nasopharyngeal carriage and clinical pneumonia [OR 1.75, p = 0.008, 95% CI 1.16–2.63 (S. pneumoniae) and OR 1.90, p = 0.004, 95% CI 1.23–2.92 (H. influenzae)]. S. aureus carriage was correlated with mortality (OR 4.01, p Conclusions Age, sex and season are important determinants of nasopharyngeal colonisation with S. pneumoniae, H. influenzae and M. catarrhalis in patients with fever in Burkina Faso. S. pneumoniae and H. influenzae carriage is associated with clinical pneumonia and S. aureus carriage is associated with mortality in patients with fever. These findings may help to understand the dynamics of colonisation and the associated transmission of these pathogens. Furthermore, understanding the determinants of nasopharyngeal colonisation and the association with disease could potentially improve the diagnosis of febrile patients.

BackgroundIn low- and middle-income countries (LMIC), the prevalence of antimicrobial resistance (AMR) is increasing. WHO recommends monitoring antibiotic use, in particular Watch antibiotics, clinical important but at risk of becoming ineffective due to increasing AMR. We investigated antibiotic use at primary care or community-level in rural Burkina Faso.MethodsDuring 2016-2017, patients aged >3 months admitted with severe acute fever to the rural hospital of Nanoro Health District, Burkina Faso, reported antibiotic use in the two weeks prior to consultation or hospitalization, which we analysed using the WHO Access, Watch, Reserve (AWaRe) classification. Most Watch antibiotics, e.g. ceftriaxone, are not recommended at primary health center level, as is also the case for ciprofloxacin in children.ResultsOf 920 participants (63.0% ≤14 years), pre-admission antibiotic use was reported by 363 (39.5%) of whom 58 (16.0%) reported more than one antibiotic. Use was more frequent among health center referrals (231, 54.0%) than among self-referred patients (131, 26.7%, p14 year olds (72, 51.1%) than 0-14 year olds (87, 30.7%) and among referrals (41, 28.1%) compared to self-referred patients (117, 42.2%). Most frequently used Watch antibiotics were ceftriaxone (114, 26.9%) and ciprofloxacin (32, 7.5%). Among antibiotics reported by referral patients, ceftriaxone and ciprofloxacin were respectively recorded 100 (36.1%) and 12 times (4.3%).ConclusionThe frequent use of Watch group antibiotics prior to presentation to the hospital in rural Burkina Faso highlights the need to address primary care, over-the-counter and informal community-level antibiotic use as part of antibiotic stewardship in LMIC, facilitating referral, access to qualified prescribers, or improving diagnostic tools in health centers.

OBJECTIVES: Areas with declining malaria transmission in sub-Saharan Africa have recently witnessed important changes in the aetiology of childhood acute febrile illness (AFI). We describe the aetiology of AFI in a high malaria transmission area in rural Burkina Faso. METHODS: In a prospective hospital-based diagnostic study, children aged 3 months to 15 years with AFI were recruited and assessed using a systematic diagnostic protocol, including blood cultures, whole blood PCR on a selection of bacterial pathogens, malaria diagnostics and a multiplex PCR on nasopharyngeal swabs targeting 21 viral and 4 bacterial respiratory pathogens. RESULTS: A total of 589 children with AFI were enrolled from whom an infectious disease was considered in 575 cases. Acute respiratory tract infections, malaria and invasive bacterial infections (IBI) accounted for 179 (31.1%), 175 (30.4%) and 75 (13%) of AFI cases respectively; 16 (21.3%) of IBI cases also had malarial parasitaemia. A viral pathogen was demonstrated from the nasopharynx in 157 children (90.7%) with respiratory tract symptoms. Of all children with viral respiratory tract infections, 154 (92.4% received antibiotics, whereas no antibiotic was provided in 13 (17%) of IBI cases. CONCLUSIONS: Viral respiratory infections are a common cause of childhood AFI in high malaria transmission areas, next to malaria and IBI. These findings highlight the importance of interventions to improve targeted treatment with antimicrobials. Most patients with viral infections received antibiotics unnecessarily, while a considerable number with IBI did not receive antibiotics. ispartof: CLINICAL MICROBIOLOGY AND INFECTION vol:27 issue:4 pages:590-596 ispartof: location:England status: published

Detection of Salmonella Paratyphi A stool carriers by conventional stool culture media is hindered by the absence of hydrogen sulphide production compared to most other Salmonella serovars. This study evaluated the detection of Salmonella Paratyphi A in stool samples using Salmonella chromogenic media compared to a conventional medium. Four chromogenic media, COMPASS Salmonella agar (Biokar Diagnostics, Beauvais, France), BBL™ CHROMagar™ Salmonella (BD Diagnostics, Erembodegem-Aalst, Belgium), Brilliance™ Salmonella agar (Oxoid Ltd., Basingstoke, UK) and Salmonella PLUS CHROMagar™ (CHROMagar, Paris, France), were compared to conventional Salmonella-Shigella agar (Oxoid Ltd.). The colony morphology of 29 freshly grown stock isolates (Salmonella and competing organisms) was assessed. The limit of detection (LOD) was also determined using saline and stool suspensions. Finally, recognizability of Salmonella Paratyphi A isolates was assessed using 20 human stool samples spiked with different concentrations of Salmonella Paratyphi A. All Salmonella Paratyphi A isolates demonstrated detectable growth with typical purple-coloured colonies that could be clearly differentiated from competing organisms on all four chromogenic media. The LOD for Salmonella Paratyphi A was 103 colony-forming units (CFU)/ml for all media, except for Brilliance agar (105 CFU/ml of stool). Salmonella Paratyphi A was easy to differentiate from competing organisms in the spiked stool samples. Colony yields improved when an enrichment step (Selenite-F broth (BD Diagnostics, Erembodegem-Aalst, Belgium)) and prolonged incubation for 48 h were performed. Chromogenic media demonstrated good specificity and a low LOD for the detection of Salmonella Paratyphi A in stool samples.

Background: Accurate and timely diagnosis of malaria is essential for disease management and surveillance. Microscopy and malaria rapid diagnostic tests (RDTs) are standard malaria diagnostics, but both methods have significant limitations. The novel automated haematology analyser XN-30 provides standard complete blood counts (CBC) as well as quantification of malaria parasitaemia at the price of an RDT. This study assessed the accuracy of XN-30 for malaria detection in a Controlled Human Malaria Infection (CHMI) study and subsequently in a phase-3 diagnostic accuracy study in Burkina Faso. Methods: Sixteen healthy malaria-naive CHMI participants were challenged according to standardized protocols by exposure to five laboratory reared Plasmodium falciparum-infected mosquitoes and sampled daily for XN-30, blood smear microscopy, RDT and qPCR analyses (NCT02836002). The blinded diagnostic accuracy study included 908 patients aged >3 months, presenting with acute febrile illness (NCT02669823). XN-30, microscopy and RDTs (HRP-2/pLDH) were performed on site, qPCR was done in retrospect. Microscopy was used as reference standard, results were corrected for qPCR confirmed submicroscopic cases. RDT results were compared to XN-30 for both microscopic and qPCR confirmed cases. Findings: All CHMI participants became parasitaemic by qPCR and XN-30 with a strong correlation for parasite density (R2=0·91). In the field study, the sensitivity and specificity of XN-30 compared to microscopy were 98.7% and 99.4% respectively (PPV 98·7%, NPV 99·4%, AUC=0·99). Three microscopy confirmed cases were not detected by XN-30. However, XN-30 detected 24 of 119 (20.2%) qPCR confirmed submicroscopic cases. The sensitivity and specificity of XN-30 to diagnose microscopic cases were higher than that of HRP-2 and pLDH RDTs. Interpretation: XN-30 is a novel rapid automated malaria diagnostic outperforming standard microscopy and RDT's at a similar price. Since it simultaneously provides haemocytometric data and allows high-throughput testing, XN-30 is an attractive diagnostic tool for malaria management and control. Funding Statement: The CHMI study was funded by PATH MVI. Sysmex Corporation provided the analyzer and reagents. The diagnostic accuracy study was funded by Sysmex Corporation. The funding sources were involved in the study design, but not in data collection, analysis and interpretation, or the preparation of the report. Declaration of Interests: AvV and QdM have a non-restricted research grant from SYSMEX, which funded the current study. None of the other authors had any conflict of interest. Ethics Approval Statement: The studies were performed in accordance with the declaration of Helsinki and GCLP guidelines. The CHMI study was approved by the central committee for research involving human subjects (CCMO) of the Netherlands (NL56659.091.16), and the Western Institutional Review Board (WIRB) in the USA. The diagnostic study was approved by the national ethical committee of Burkina Faso (ref 2015-01-006), the internal review board of IRSS (ref A03-2016/CEIRES) the ethical committee of the university hospital of Antwerp (ref 15/47/492) and the institutional review board of the Institute of Tropical Medicine Antwerp (ref 1029/15).

Background Bloodstream infections (BSI) caused by Salmonella Typhi and invasive non-Typhoidal Salmonella (iNTS) frequently affect children living in rural sub-Saharan Africa but data about incidence and serotype distribution are rare. Objective The present study assessed the population-based incidence of Salmonella BSI and severe malaria in a Health and Demographic Surveillance System in a rural area with seasonal malaria transmission in Nanoro, Burkina Faso. Methods Children between 2 months—15 years old with severe febrile illness were enrolled during a one-year surveillance period (May 2013—May 2014). Thick blood films and blood cultures were sampled and processed upon admission. Population-based incidences were corrected for non-referral, health seeking behavior, non-inclusion and blood culture sensitivity. Adjusted incidence rates were expressed per 100,000 person-years of observations (PYO). Results Among children < 5 years old, incidence rates for iNTS, Salmonella Typhi and severe malaria per 100,000 PYO were 4,138 (95% Confidence Interval (CI): 3,740–4,572), 224 (95% CI: 138–340) and 2,866 (95% CI: 2,538–3,233) respectively. Among those aged 5–15 years, corresponding incidence rates were 25 (95% CI: 8–60), 273 (95% CI: 203–355) and 135 (95% CI: 87–195) respectively. Most iNTS occurred during the peak of the rainy season and in parallel with the increase of Plasmodium falciparum malaria; for Salmonella Typhi no clear seasonal pattern was observed. Salmonella Typhi and iNTS accounted for 13.3% and 55.8% of all 118 BSI episodes; 71.6% of iNTS (48/67) isolates were Salmonella enterica serovar Typhimurium and 25.4% (17/67) Salmonella enterica serovar Enteritidis; there was no apparent geographical clustering. Conclusion The present findings from rural West-Africa confirm high incidences of Salmonella Typhi and iNTS, the latter with a seasonal and Plasmodium falciparum-related pattern. It urges prioritization of the development and implementation of Salmonella Typhi as well as iNTS vaccines in this setting.