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Prenatal multiple micronutrient supplementation (MMS) and lipid-based nutrient supplementation (LNS) can improve birth outcomes relative to iron-folic acid supplementation (IFA); however, effects on child postnatal growth remain unclear.The aim was to compare the effect of prenatal MMS, medium-quantity LNS (MQ-LNS), and IFA on child growth up to 2 y of age.We conducted a cluster randomized controlled trial of prenatal nutritional supplementation in Madarounfa, Niger. Villages were randomly assigned for pregnant women to receive IFA (17 villages, 1105 women), MMS (18 villages, 1083 women) or MQ-LNS (18 villages, 1144 women). Pregnant women received nutritional supplements weekly until delivery, and children were followed up monthly from 6-8 wk to 24 mo of age. We assessed the effect of prenatal MMS and MQ-LNS compared with IFA and the effect of prenatal MMS compared with MQ-LNS on child length-for-age z scores (LAZ), weight-for-age z scores (WAZ), and weight-for-length z scores (WLZ) at 24 mo of age using generalized linear models. In secondary analyses, we used mixed-effects models to assess the trajectories of anthropometric z scores longitudinally from 6-8 wk to 24 mo.Compared with IFA, MMS and MQ-LNS had no effect on child LAZ, WAZ, or WLZ at 24 mo of age (P0.05). Children in the MQ-LNS arm had significantly higher mid-upper arm circumference at 24 mo than children in the MMS arm: mean difference 0.50 cm (95% CI 0.10, 0.91 cm). WAZ and WLZ trajectories were more negative in the MQ-LNS arm compared with IFA and MMS, with lower z scores from 14 to 20 mo of age. However, WAZ and WLZ trajectories converged after 20 mo of age, and there were no differences by 24 mo of age.Prenatal MMS and MQ-LNS had limited effect on anthropometric measures of child growth up to 24 mo of age as compared with IFA in rural Niger.

Background Malaria transmission is highly seasonal in Niger. Despite the introduction of seasonal malaria chemoprevention (SMC) in the Magaria District, malaria incidence remains high, and the epidemiology of malaria in the community is not well-understood. Methods Four cross-sectional, household-based malaria prevalence surveys were performed in the Magaria District of Niger between October 2016 and February 2018. Two occurred during the peak malaria season and two during the low malaria season. Individuals in each of three age strata (3–59 months, 5–9 years, and 10 years and above) were sampled in randomly-selected households. Capillary blood was collected by fingerprick, thick and thin blood films were examined. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 396 households during the high-season surveys and 266 households during the low-season surveys. Results Prevalence of parasitaemia was highest in children aged 5–9 years during all four surveys, ranging between 53.6% (95%CI 48.8–63.6) in February 2018 and 73.2% (66.2–79.2) in September 2017. Prevalence of parasitaemia among children aged 3–59 months ranged between 39.6% (33.2–46.4) in February 2018 and 51.9% (45.1–58.6) in October 2016. Parasite density was highest in children aged 3–59 months during all four surveys, and was higher in high season surveys than in low season surveys among all participants. The prevalence of gametocytaemia in children aged 3–59 months ranged between 9.9% (6.5–14.8) in February 2018 and 19.3% (14.6–25.2) in October 2016. The prevalence of gametocytaemia in children aged 5–9 years ranged between 6.3% (3.5–11.1) in February 2018 and 18.5% (12.7–26.1) in October 2016. Conclusions Asymptomatic malaria infection is highly prevalent in this area, even during the season with low incidence of clinical malaria. The high prevalence of parasitaemia in children aged 5–9 years warrants considering their inclusion in SMC programmes in this context.

SummaryObjectiveWhole genome sequencing (WGS) of extended-spectrum β-lactamase-producingEscherichia coli(ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. colifaecal isolates in rural Southern Niger.MethodsStools of 383 healthy participants were collected among which 92.4% were ESBL-E. colicarriers; 90 of these ESBL-E. colicontaining stools (109 ESBL-E. coliisolates) were further analysed by WGS, using short- and long-reads.ResultsMost isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. TheblaCTX-M-15gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne,blaCTX-M-15was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis ofblaCTX-M-15in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome.ConclusionsMassive prevalence of community faecal carriage of CTX-M-15-producingE. coliwas observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration ofblaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.

Background Nutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine. Methods and findings We nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron–folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6–8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear. Conclusions This study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings. Trial registration ClinicalTrials.gov NCT02145000., Sheila Isanaka and co-workers study nutrient supplementation and infants’ immune responses to rotavirus vaccination., Author summary Why was this study done? The World Health Organization recommends that all children be vaccinated against rotavirus, the most common cause of severe childhood diarrhea and a major cause of morbidity and mortality worldwide. Two oral rotavirus vaccines have been shown to be highly efficacious against childhood diarrhea in high- and middle-income countries (85%–98%), but, virtually, all trials in sub-Saharan Africa and South Asia have shown lower immune response and much lower efficacy (40%–64%), leaving many children unprotected. As the development of the immune cells that support vaccine response specifically depend on an adequate supply of micronutrients, nutritional supplementation has been considered as a potential adjunctive intervention to improve oral vaccine performance. What did the researchers do and find? We nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron–folic acid [IFA]) on infant immune response. This study found no effect of the type of prenatal nutrient supplementation on immune response in this setting; however, the immune response appeared to vary by previous exposure to rotavirus. What do these findings mean? To improve the oral vaccine immunogenicity gap between low- and high-income countries, a more complete understanding of the factors influencing immunogenicity and a reliable correlate of protection are needed. Without improvement in oral vaccine performance, alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings.

Background Direct detection of SARS-CoV-2 viral proteins in nasopharyngeal swabs using lateral flow immunoassays is a simple, fast and cheap approach to diagnose the infection. Aims and Methods The performance of 6 SARS-CoV-2 antigen rapid diagnostic tests has been assessed in 634 hospitalized patients or outpatients including 297 patients found to be positive for SARS-CoV-2 RNA by means of RT-PCR and 337 patients presumed to be SARS-CoV-2 RNA-negative. Results The specificity of SARS-CoV-2 RDTs was generally high (398.5%). One assay had a lower specificity of 93.2%. The overall sensitivity of the 6 RDTs was variable, from 32.3% to 61.7%. Sensitivity correlated with the delay of sampling after the onset of symptoms and the viral load estimated by the Ct value in RT-PCR. Four out of 6 RDTs tested achieved sensitivities 380% when clinical specimens were collected during the first 3 days following symptom onset or with a Ct value ≤25. Conclusions The present study shows that SARS-CoV-2 antigen can be easily and reliably detected by RDTs. These tests are easy and rapid to perform. However, the specificity and sensitivity of COVID-19 antigen RDTs may widely vary across different tests and must therefore be carefully evaluated before releasing these assays for realworld applications.

S U M M A R Y: Background: The risk of healthcare-associated infections is exacerbated by poor hygiene practices in health care facilities and can contribute to increased patient morbidity and mortality. In low-income settings, caregivers play a key role in maintaining proper hygiene during inpatient stays. We aimed to explore caregivers' knowledge, perceptions and practices related to hospital hygiene in a rural, sub-Saharan African setting. Methods: We conducted an exploratory qualitative study among caregivers of children admitted to an inpatient therapeutic feeding center in Madarounfa, Niger. Individual interviews with 28 caregivers of hospitalized children were conducted to explore their knowledge, perceptions and practices of hygiene in the health facility. Findings: Caregivers described a broad understanding of hygiene and reported knowledge of its importance in the hospital, particularly to prevent disease transmission and protect child health. Hygiene was perceived as a collective rather than individual responsibility. Caregivers reported on the poor hygiene practice of others and cited a lack of space and hygiene materials as barriers to correct hygiene practice. Caregivers described educational sessions and informal sharing with other caregivers as tools to gain knowledge and improve practice. Conclusion: This exploratory study is unique in describing the perspective of caregivers in a low-resource hospital setting, a group often underrepresented when designing health interventions to improve hospital hygiene. Our findings suggest a strong knowledge of hospital hygiene among caregivers in this setting, with positive perception of its importance in health promotion. Poor individual practice was reported but may be improved through additional education and provision of hygiene materials.

Poor adherence to seasonal malaria chemoprevention (SMC) might affect the protective effectiveness of SMC. Here, we evaluated the population pharmacokinetic properties of amodiaquine and its active metabolite, desethylamodiaquine, in children receiving SMC under directly observed ideal conditions (n = 136), and the adherence of SMC at an implementation phase in children participating in a case-control study to evaluate SMC effectiveness (n = 869). Amodiaquine and desethylamodiaquine concentration-time profiles were described simultaneously by two-compartment and three-compartment disposition models, respectively. The developed methodology to evaluate adherence showed a sensitivity of 65-71% when the first dose of SMC was directly observed and 71-73% when no doses were observed in a routine programmatic setting. Adherence simulations and measured desethylamodiaquine concentrations in the case-control children showed complete adherence (all doses taken) in < 20% of children. This result suggests that more efforts are needed urgently to improve the adherence to SMC among children in this area.

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 War-wounded civilians in Middle East countries are at risk of post-traumatic osteomyelitis (PTO). We aimed to describe and compare the bacterial etiology and proportion of first-line antibiotics resistant bacteria (FLAR) among PTO cases in civilians from Syria, Iraq and Yemen admitted to the reconstructive surgical program of Médecins Sans Frontières (MSF) in Amman, Jordan, and to identify risk factors for developing PTO with FLAR bacteria. Methods We retrospectively analyzed the laboratory database of the MSF program. Inclusion criteria were: patients from Iraq, Yemen or Syria, admitted to the Amman MSF program between October 2006 and December 2016, with at least one bone biopsy sample culture result. Only bone samples taken during first orthopedic surgery were included in the analysis. To assess factors associated with FLAR infection, logistic regression was used to estimate odds ratio (ORs) and 95% confidence intervals (CI). Results 558 (76.7%) among 727 patients included had ≥1 positive culture results. 318 were from Iraq, 140 from Syria and 100 from Yemen. Median time since injury was 19 months [IQR 8–40]. Among the 732 different bacterial isolates, we identified 228 Enterobacteriaceae (31.5%), 193 Staphylococcus aureus (26.3%), 99 Pseudomonas aeruginosa (13.5%), and 21 Acinetobacter baumanii (2.8%). Three hundred and sixty four isolates were FLAR: 86.2% of Enterobacteriaceae, 53.4% of Pseudomonas aeruginosa, 60.5% of S. aureus and 45% of Acinetobacter baumannii. There was no difference in bacterial etiology or proportion of FLAR according to the country of origin. In multivariate analysis, a FLAR infection was associated with an infection of the lower extremity, with a time since the injury ≤12 months compared with time > 30 months and with more than 3 previous surgeries. Conclusions Enterobacteriaceae were frequently involved in PTO in war wounded civilians from Iraq, Yemen and Syria between 2006 and 2016. Proportion of FLAR was high, particularly among Enterobacteriaceae, regardless of country of origin. Electronic supplementary material The online version of this article (10.1186/s12879-019-3741-9) contains supplementary material, which is available to authorized users.

Using quantitative PCR diagnostics in a phase 3 clinical trial of Rotasiil in Niger, we identified Shigella, Cryptosporidium, rotavirus, and heat-stabile toxin-producing Escherichia coli to be the top 4 leading etiologies of moderate-to-severe diarrhea in children 0-2 years of age., Background High-resolution data on the etiology of childhood diarrhea in countries with the highest burden and mortality remain sparse and are needed to inform burden estimates and prioritize interventions. Methods We tested stool specimens collected between October 2014 and December 2017 from children under 2 years of age from the per-protocol population of a placebo-controlled clinical trial of a bovine rotavirus pentavalent vaccine (Rotasiil) in Niger. We tested 1729 episodes of moderate-to-severe diarrhea (Vesikari score ≥ 7) using quantitative PCR and estimated pathogen-specific burdens by age, season, severity, and trial intervention arm. Results The 4 pathogens with the highest attributable incidence of diarrhea were Shigella (7.2 attributable episodes per 100 child-years; 95% confidence interval: 5.2, 9.7), Cryptosporidium (6.5; 5.8, 7.2), rotavirus (6.4; 5.9, 6.7), and heat-stabile toxin-producing enterotoxigenic Escherichia coli (ST-ETEC) (6.2; 3.1, 7.7). Cryptosporidium was the leading etiology of severe diarrhea (Vesikari score ≥ 11) and diarrhea requiring hospitalization. Shigella was the leading etiology of diarrhea in children 12-23 months of age but also had a substantial burden in the first year of life, with 60.5% of episodes of severe shigellosis occurring in infants. Shigella, Cryptosporidium, and ST-ETEC incidence peaked during the warmer and wetter period and coincided with peak all-cause diarrhea incidence. Conclusions In this high-burden setting, the leading diarrheal pathogens were Shigella, Cryptosporidium, rotavirus, and ST-ETEC, and each was disproportionately seen in infants. Vaccine development should target these pathogens, and the impact of vaccine schedule on diarrhea burden in the youngest children will need to be considered.

Summary Background Real-time PCR is recommended to detect SARS-CoV-2 infection. However, PCR availability is restricted in most countries. Rapid diagnostic tests are considered acceptable alternatives, but data are lacking on their performance. We assessed the performance of four antibody-based rapid diagnostic tests and one antigen-based rapid diagnostic test for detecting SARS-CoV-2 infection in the community in Cameroon. Methods In this clinical, prospective, diagnostic accuracy study, we enrolled individuals aged at least 21 years who were either symptomatic and suspected of having COVID-19 or asymptomatic and presented for screening. We tested peripheral blood for SARS-CoV-2 antibodies using the Innovita (Biological Technology; Beijing, China), Wondfo (Guangzhou Wondfo Biotech; Guangzhou, China), SD Biosensor (SD Biosensor; Gyeonggi-do, South Korea), and Runkun tests (Runkun Pharmaceutical; Hunan, China), and nasopharyngeal swabs for SARS-CoV-2 antigen using the SD Biosensor test. Antigen rapid diagnostic tests were compared with Abbott PCR testing (Abbott; Abbott Park, IL, USA), and antibody rapid diagnostic tests were compared with Biomerieux immunoassays (Biomerieux; Marcy l'Etoile, France). We retrospectively tested two diagnostic algorithms that incorporated rapid diagnostic tests for symptomatic and asymptomatic patients using simulation modelling. Findings 1195 participants were enrolled in the study. 347 (29%) tested SARS-CoV-2 PCR-positive, 223 (19%) rapid diagnostic test antigen-positive, and 478 (40%) rapid diagnostic test antibody-positive. Antigen-based rapid diagnostic test sensitivity was 80·0% (95% CI 71·0–88·0) in the first 7 days after symptom onset, but antibody-based rapid diagnostic tests had only 26·8% sensitivity (18·3–36·8). Antibody rapid diagnostic test sensitivity increased to 76·4% (70·1–82·0) 14 days after symptom onset. Among asymptomatic participants, the sensitivity of antigen-based and antibody-based rapid diagnostic tests were 37·0% (27·0–48·0) and 50·7% (42·2–59·1), respectively. Cohen's κ showed substantial agreement between Wondfo antibody rapid diagnostic test and gold-standard ELISA (κ=0·76; sensitivity 0·98) and between Biosensor and ELISA (κ=0·60; sensitivity 0·94). Innovita (κ=0·47; sensitivity 0·93) and Runkun (κ=0·43; sensitivity 0·76) showed moderate agreement. An antigen-based retrospective algorithm applied to symptomatic patients showed 94·0% sensitivity and 91·0% specificity in the first 7 days after symptom onset. For asymptomatic participants, the algorithm showed a sensitivity of 34% (95% CI 23·0–44·0) and a specificity of 92·0% (88·0–96·0). Interpretation Rapid diagnostic tests had good overall sensitivity for diagnosing SARS-CoV-2 infection. Rapid diagnostic tests could be incorporated into efficient testing algorithms as an alternative to PCR to decrease diagnostic delays and onward viral transmission. Funding Medecins Sans Frontieres WACA and Medecins Sans Frontieres OCG. Translations For the French and Spanish translations of the abstract see Supplementary Materials section.

Background Rotavirus vaccination is recommended in all countries to reduce the burden of diarrhea-related morbidity and mortality in children. In resource-limited settings, rotavirus vaccination in the national immunization program has important cost implications, and evidence for protection beyond the first year of life and against the evolving variety of rotavirus strains is important. We assessed the extended and strain-specific vaccine efficacy of a heat-stable, affordable oral rotavirus vaccine (Rotasiil, Serum Institute of India, Pune, India) against severe rotavirus gastroenteritis (SRVGE) among healthy infants in Niger. Methods and findings From August 2014 to November 2015, infants were randomized in a 1:1 ratio to receive 3 doses of Rotasiil or placebo at approximately 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and graded using the Vesikari score. The primary endpoint was vaccine efficacy of 3 doses of vaccine versus placebo against a first episode of laboratory-confirmed SRVGE (Vesikari score ≥ 11) from 28 days after dose 3, as previously reported. At the time of the primary analysis, median age was 9.8 months. In the present paper, analyses of extended efficacy were undertaken for 3 periods (28 days after dose 3 to 1 year of age, 1 to 2 years of age, and the combined period 28 days after dose 3 to 2 years of age) and by individual rotavirus G type. Among the 3,508 infants included in the per-protocol efficacy analysis (mean age at first dose 6.5 weeks; 49% male), the vaccine provided significant protection against SRVGE through the first year of life (3.96 and 9.98 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 60.3%, 95% CI 43.6% to 72.1%) and over the entire efficacy follow-up period up to 2 years of age (2.13 and 4.69 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 54.7%, 95% CI 38.1% to 66.8%), but the difference was not statistically significant in the second year of life. Up to 2 years of age, rotavirus vaccination prevented 2.56 episodes of SRVGE per 100 child-years. Estimates of efficacy against SRVGE by individual rotavirus genotype were consistent with the overall protective efficacy. Study limitations include limited generalizability to settings with administration of oral polio virus due to low concomitant administration, limited power to assess vaccine efficacy in the second year of life owing to a low number of events among older children, potential bias due to censoring of placebo children at the time of study vaccine receipt, and suboptimal adapted severity scoring based on the Vesikari score, which was designed for use in settings with high parental literacy. Conclusions Rotasiil provided protection against SRVGE in infants through an extended follow-up period of approximately 2 years. Protection was significant in the first year of life, when the disease burden and risk of death are highest, and against a changing pattern of rotavirus strains during the 2-year efficacy period. Rotavirus vaccines that are safe, effective, and protective against multiple strains represent the best hope for preventing the severe consequences of rotavirus infection, especially in resource-limited settings, where access to care may be limited. Studies such as this provide valuable information for the planning of national immunization programs and future vaccine development. Trial registration ClinicalTrials.gov NCT02145000., Sheila Isanaka and co-workers report extended follow-up of a rotavirus vaccine trial in Niger., Author summary Why was this study done? The World Health Organization (WHO) recommends rotavirus vaccine use in all countries, but several questions remain for countries that have not yet implemented rotavirus vaccination or are weighing different vaccine options. In resource-limited settings, where rotavirus vaccine delivery has important cost implications, evidence for protection beyond the first year of life and against the evolving variety of rotavirus strains is important. We previously reported on the efficacy and safety of Rotasiil (Serum Institute of India, Pune, India), a heat-stable, affordable oral rotavirus vaccine that was WHO prequalified in 2018, against severe rotavirus gastroenteritis (SRVGE) among healthy infants in Niger. What did the researchers do and find? In the present analysis, we assessed the extended and strain-specific vaccine efficacy of Rotasiil in children up to 24 months of age. Rotasiil provided protection against SRVGE in infants through an extended follow-up period and against a changing pattern of rotavirus strains during the 2-year efficacy period. What do these findings mean? Vaccines that are safe, effective, and protective against multiple strains represent the best hope for preventing the severe consequences of rotavirus infection, and can be expected to greatly reduce the burden of rotavirus disease.

Numerous SARS-CoV-2 rapid serological tests have been developed, but their accuracy has usually been assessed using very few samples, and rigorous comparisons between these tests are scarce. In this study, we evaluated and compared 10 commercially-available SARS-CoV2 rapid serological tests using the STARD methodology (Standards for Reporting of Diagnostic Accuracy Studies). 250 sera from 159 PCR-confirmed SARS-CoV-2 patients (collected from 0 to 32 days after onset of symptoms) were tested with rapid serological tests. Control sera (N=254) were retrieved from pre-COVID periods from patients with other coronavirus infections (N=11), positive rheumatoid factors (N=3), IgG/IgM hyperglobulinemia (N=9), malaria (n=5), or no documented viral infection (N=226). All samples were tested using rapid lateral flow immunoassays (LFIA) from ten manufacturers. Only four tests achieved ≥98% specificity, with other tests ranging from 75.7%-99.2%. Sensitivities varied by the day of sample collection, from 31.7%-55.4% (Days 0-9), 65.9%92.9% (Days 10-14), and 81.0%-95.2% (>14 days) after the onset of symptoms, respectively. Only three tests evaluated met French Health Authorities’ thresholds for SARS-CoV-2 serological tests (≥90% sensitivity + ≥98% specificity). Overall, the performances between tests varied greatly, with only a third meeting acceptable specificity and sensitivity thresholds. Knowing the analytical performance of these tests will allow clinicians to use them with more confidence, could help determine the general population’s immunological status, and may diagnose some patients with false-negative RT-PCR results.

Numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid serological tests have been developed, but their accuracy has usually been assessed using very few samples, and rigorous comparisons between these tests are scarce. In this study, we evaluated and compared 10 commercially available SARS-CoV-2 rapid serological tests using the STARD (Standards for Reporting of Diagnostic Accuracy Studies) methodology., Numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid serological tests have been developed, but their accuracy has usually been assessed using very few samples, and rigorous comparisons between these tests are scarce. In this study, we evaluated and compared 10 commercially available SARS-CoV-2 rapid serological tests using the STARD (Standards for Reporting of Diagnostic Accuracy Studies) methodology. Two hundred fifty serum samples from 159 PCR-confirmed SARS-CoV-2 patients (collected 0 to 32 days after the onset of symptoms) were tested with rapid serological tests. Control serum samples (n = 254) were retrieved from pre-coronavirus disease (COVID) periods from patients with other coronavirus infections (n = 11), positivity for rheumatoid factors (n = 3), IgG/IgM hyperglobulinemia (n = 9), malaria (n = 5), or no documented viral infection (n = 226). All samples were tested using rapid lateral flow immunoassays (LFIAs) from 10 manufacturers. Only four tests achieved ≥98% specificity, with the specificities ranging from 75.7% to 99.2%. The sensitivities varied by the day of sample collection after the onset of symptoms, from 31.7% to 55.4% (days 0 to 9), 65.9% to 92.9% (days 10 to 14), and 81.0% to 95.2% (>14 days). Only three of the tests evaluated met French health authorities’ thresholds for SARS-CoV-2 serological tests (≥90% sensitivity and ≥98% specificity). Overall, the performances varied greatly between tests, with only one-third meeting acceptable specificity and sensitivity thresholds. Knowledge of the analytical performances of these tests will allow clinicians and, most importantly, laboratorians to use them with more confidence; could help determine the general population’s immunological status; and may help diagnose some patients with false-negative real-time reverse transcription-PCR (RT-PCR) results.

Background In East Africa, fishing communities are considered most-at-risk populations for the acquisition of HIV. We estimated HIV prevalence and assessed progress towards the UNAIDS 90–90-90 targets along the HIV treatment cascade in 12 fishing communities surrounding Lakes Edward and George, Uganda. Methods We conducted a cross-sectional household-based survey between September and November 2016. All adults between 15 and 69 years old were eligible to participate. Children below 15 years old were eligible for HIV testing if either parent was HIV-positive. Viral load testing was done for all HIV-infected individuals. Logistic regression models adjusted for sociodemographic-behavioral variables were used to assess the association between occupation and HIV positivity. Results Overall, 1738 adults (959 women, 779 men) and 148 children were included. Adult inclusion rate was 96.0%. Of the men, 58% reported to be fishermen. The HIV-prevalence among adults was 17.5% (95%CI: 15.8–19.4) and 6.1% (95%CI: 3.1–11.4) among HIV-exposed children. HIV prevalence was higher among women than among men (20.9% vs. 13.5%, p p p Conclusions HIV prevalence was high in these fishing communities, particularly among women and fishermen. Important progress has been made along the HIV treatment cascade, and the UNAIDS goal for viral suppression in population was achieved. However, gaps remain and HIV care strategies focusing on young people are urgently needed. HIV preventive interventions should target particularly women, young people and fishermen though HIV preventive and care services should remain available to the whole fishing communities.

SCOPUS: no.j, info:eu-repo/semantics/published

Low-resource settings are disproportionately burdened by infectious diseases and antimicrobial resistance. Good quality clinical bacteriology through a well functioning reference laboratory network is necessary for effective resistance control, but low-resource settings face infrastructural, technical, and behavioural challenges in the implementation of clinical bacteriology. In this Personal View, we explore what constitutes successful implementation of clinical bacteriology in low-resource settings and describe a framework for implementation that is suitable for general referral hospitals in low-income and middle-income countries with a moderate infrastructure. Most microbiological techniques and equipment are not developed for the specific needs of such settings. Pending the arrival of a new generation diagnostics for these settings, we suggest focus on improving, adapting, and implementing conventional, culture-based techniques. Priorities in low-resource settings include harmonised, quality assured, and tropicalised equipment, consumables, and techniques, and rationalised bacterial identification and testing for antimicrobial resistance. Diagnostics should be integrated into clinical care and patient management; clinically relevant specimens must be appropriately selected and prioritised. Open-access training materials and information management tools should be developed. Also important is the need for onsite validation and field adoption of diagnostics in low-resource settings, with considerable shortening of the time between development and implementation of diagnostics. We argue that the implementation of clinical bacteriology in low-resource settings improves patient management, provides valuable surveillance for local antibiotic treatment guidelines and national policies, and supports containment of antimicrobial resistance and the prevention and control of hospital-acquired infections.

Growing data suggest that antimicrobial-resistant bacterial infections are common in low- and middle-income countries. This review summarises the microbiology of key bacterial syndromes encountered in West Africa and estimates the prevalence of antimicrobial resistance (AMR) that could compromise first-line empirical treatment. We systematically searched for studies reporting on the epidemiology of bacterial infection and prevalence of AMR in West Africa within key clinical syndromes. Within each syndrome, the pooled proportion and 95% confidence interval were calculated for each pathogen-antibiotic pair using random-effects models. Among 281 full-text articles reviewed, 120 met the eligibility criteria. The majority of studies originated from Nigeria (70; 58.3%), Ghana (15; 12.5%) and Senegal (15; 12.5%). Overall, 43 studies (35.8%) focused on urinary tract infections (UTI), 38 (31.7%) on bloodstream infections (BSI), 27 (22.5%) on meningitis, 7 (5.8%) on diarrhoea and 5 (4.2%) on pneumonia. Children comprised the majority of subjects. Studies of UTI reported moderate to high rates of AMR to commonly used antibiotics including evidence of the emergence of cephalosporin resistance. We found moderate rates of AMR among common bloodstream pathogens to typical first-line antibiotics including ampicillin, cotrimoxazole, gentamicin and amoxicillin/clavulanate. Among S. pneumoniae strains isolated in patients with meningitis, levels of penicillin resistance were low to moderate with no significant resistance noted to ceftriaxone or cefotaxime. AMR was common in this region, particularly in hospitalized patients with BSI and both outpatient and hospitalized patients with UTI. This raises concern given the limited diagnostic capability and second-line treatment options in the public sector in West Africa.

Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa.We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3.Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception.Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000 .).

ObjectivesIn resource-limited settings, screening pregnant women for syphilis using rapid diagnostic tests (RDTs) is a key tool in the prevention of congenital syphilis. However, most syphilis RDTs detect only treponemal antibodies (T-RDT), meaning antibiotics may be provided unnecessarily to previously treated pregnant women, particularly in non-venereal treponematoses endemic regions. We estimated the potential reduction in overtreatment when comparing T-RDT (SD Bioline) to a newer rapid test (Dual Path Platform (DPP) Screen and Confirm Assay, Chembio) detecting both treponemal and non-treponemal antibodies.MethodsPregnant women in Déou, Burkina Faso, screened for syphilis during antenatal care (ANC) visits were prospectively enrolled in the study after providing consent. DPP and T-RDT tests were performed on whole blood specimens. Plasma was tested in an international reference laboratory by Treponema pallidum passive particle agglutination (TPPA) and quantitative rapid plasma reagin (RPR). Presumptive active syphilis was defined as a result that was both TPPA and RPR reactive.ResultsOf the 242 pregnant women included in the study, 91 (37.6%) had presumptive active syphilis and 19.0% had RPR titres ≥8. DPP testing did not reduce the number of pregnant women who would have been overtreated compared with T-RDT (0.0% vs 2.5%; p=0.218) and had a higher proportion of underdiagnosis (48.4% vs 2.2%; pConclusionIn the first evaluation comparing DPP with traditional screening methods in pregnant women, we saw no reduction in unnecessarily treated syphilis and an underestimation of those needing treatment. High seroprevalence in the population may indicate the presence of other treponemal infections in the area, and further study of DPP in a variety of Sahelian and other contexts is warranted.

Background Rapid diagnostic tests (RDT) for malaria are common, but their performance varies. Tests using histidine-rich protein 2 (HRP2) antigen are most common, and many have high sensitivity. HRP2 tests can remain positive for weeks after treatment, limiting their specificity and usefulness in high-transmission settings. Tests using Plasmodium lactate dehydrogenase (pLDH) have been less widely used but have higher specificity, mostly due to a much shorter time to become negative. Methods A prospective, health centre-based, diagnostic evaluation of two malaria RDTs was performed in rural Niger during the high malaria transmission season (3–28 October, 2017) and during the low transmission season (28 January–31 March, 2018). All children under 5 years of age presenting with fever (axillary temperature > 37.5 °C) or history of fever in the previous 24 h were eligible. Capillary blood was collected by finger prick. The SD Bioline HRP2 (catalog: 05FK50) and the CareStart pLDH(pan) (catalog: RMNM-02571) were performed in parallel, and thick and thin smears were prepared. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 279 children with microscopy-confirmed malaria during each transmission season. Results In the high season, the sensitivity of both tests was estimated at > 99%, but the specificity of both tests was lower: 58.0% (95% CI 52.1–63.8) for the pLDH test and 57.4% (95% CI 51.5–63.1) for the HRP2 test. The positive predictive value was 66.3% (95% CI 61.1–71.2) for both tests. In the low season, the sensitivity of both tests dropped: 91.0% (95% CI 85.3–95.0) for the pLDH test and 85.8% (95% CI 79.3–90.9) for the HRP2 test. The positive predictive value remained low for both tests in the low season: 60.5% (95% CI 53.9–66.8) for the pLDH test and 61.9% (55.0–68.4) for the HRP2 test. Performance was similar across different production lots, gender, age of the children, and, during the high season, time since the most recent distribution of seasonal malaria chemoprevention. Conclusions The low specificity of the pLDH RDT in this setting was unexpected and is not easily explained. As the pLDH test continues to be introduced into new settings, the questions raised by this study will need to be addressed.

Xpert MTB/RIF (Xpert) and culture are the most reliable methods for tuberculosis diagnosis but are still poorly accessible in many low-resource countries. We aimed to assess the effects of OMNIgene Sputum (OM-S) and ethanol in preserving sputum for Xpert and OM-S for mycobacterial growth indicator tube (MGIT) testing over periods of 15 and 8 days, respectively. Sputum samples were collected from newly diagnosed smear-positive patients. For Xpert, pooled samples were split into 5 aliquots: 3 for Xpert on days 0, 7, and 15 without additive and 2 with either OM-S or ethanol at day 15. For MGIT, 2 aliquots were tested without preservative and 2 with OM-S at 0 and 8 days. Totals of 48 and 47 samples were included in the analysis for Xpert and culture. With Xpert, using day 0 as a reference, untreated samples stored for 7 and 15 days showed concordances of 45/46 (97.8%) and 46/48 (95.8%). For samples preserved with OM-S or ethanol for 15 days compared with untreated samples processed at day 0 or after 15 days, OM-S concordances were 46/48 (95.8%) and 47/48 (97.9%), while those of ethanol were 44/48 (91.7%) and 45/48 (93.8%). With MGIT, concordances between untreated and OM-S-treated samples were 21/41 (51.2%) at day 0 and 21/44 (47.7%) at day 8. In conclusion, Xpert equally detected tuberculosis in OM-S-treated and untreated samples up to 15 days but showed slightly lower detection in ethanol-treated samples. Among OM-S-treated samples, MGIT positivity was significantly lower than in untreated samples at both time points.

ObjectivesRoutine amoxicillin for children with uncomplicated severe acute malnutrition raises concerns of increasing antibiotic resistance. We performed an ancillary study nested within a double-blind, placebo-controlled trial in Niger testing the role of routine 7 day amoxicillin therapy in nutritional recovery of children 6 to 59 months of age with uncomplicated severe acute malnutrition.MethodsWe screened 472 children for rectal carriage of ESBL-producing Enterobacteriaceae (ESBL-E) as well as their household siblings under 5 years old, at baseline and Week 1 (W1) and Week 4 (W4) after start of therapy, and characterized strains by WGS. ClinicalTrials.gov: NCT01613547.ResultsCarriage in index children at baseline was similar in the amoxicillin and the placebo groups (33.8% versus 27.9%, P = 0.17). However, acquisition of ESBL-E in index children at W1 was higher in the amoxicillin group than in the placebo group (53.7% versus 32.2%, adjusted risk ratio = 2.29, P = 0.001). Among 209 index and sibling households possibly exposed to ESBL-E transmission, 16 (7.7%) had paired strains differing by ≤10 SNPs, suggesting a high probability of transmission. This was more frequent in households from the amoxicillin group than from the placebo group [11.5% (12/104) versus 3.8% (4/105), P = 0.04].ConclusionsAmong children exposed to amoxicillin, ESBL-E colonization was more frequent and the risk of transmission to siblings higher. Routine amoxicillin should be carefully balanced with the risks associated with ESBL-E colonization.

High-quality evidence supporting a community-based treatment protocol for children with severe acute malnutrition, including routine antibiotic use at admission to a nutritional treatment program, remains limited. In view of the costs and consequences of emerging resistance associated with routine antibiotic use, more evidence is required to support this practice.In a double-blind, placebo-controlled trial in Niger, we randomly assigned children who were 6 to 59 months of age and had uncomplicated severe acute malnutrition to receive amoxicillin or placebo for 7 days. The primary outcome was nutritional recovery at or before week 8.A total of 2412 children underwent randomization, and 2399 children were included in the analysis. Nutritional recovery occurred in 65.9% of children in the amoxicillin group (790 of 1199) and in 62.7% of children in the placebo group (752 of 1200). There was no significant difference in the likelihood of nutritional recovery (risk ratio for amoxicillin vs. placebo, 1.05; 95% confidence interval [CI], 0.99 to 1.12; P=0.10). In secondary analyses, amoxicillin decreased the risk of transfer to inpatient care by 14% (26.4% in the amoxicillin group vs. 30.7% in the placebo group; risk ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02).We found no benefit of routine antibiotic use with respect to nutritional recovery from uncomplicated severe acute malnutrition in Niger. In regions with adequate infrastructure for surveillance and management of complications, health care facilities could consider eliminating the routine use of antibiotics in protocols for the treatment of uncomplicated severe acute malnutrition. (Funded by Médecins sans Frontières Operational Center Paris; ClinicalTrials.gov number, NCT01613547.).

Background In Niger, malaria transmission is markedly seasonal with most of the disease burden occurring in children during the rainy season. Seasonal malaria chemoprevention (SMC) with amodiaquine plus sulfadoxine– pyrimethamine (AQ + SP) is recommended in the country to be administered monthly just before and during the rainy season. Moreover, clinical decisions on use of SP for intermittent preventive treatment in pregnancy (IPTp) now depend upon the validated molecular markers for SP resistance in Plasmodium falciparum observed in the local parasite population. However, little is known about molecular markers of resistance for either SP or AQ in the south of Niger. To address this question, clinical samples which met clinical and biological criteria, were collected in Gabi, Madarounfa district, Maradi region, Niger in 2011–2012 (before SMC implementation). Molecular markers of resistance to pyrimethamine (pfdhfr), sulfadoxine (pfdhps) and amodiaquine (pfmdr1) were assessed by DNA sequencing. Results Prior to SMC implementation, the samples showed a high proportion of clinical samples that carried the pfdhfr 51I/59R/108N haplotype associated with resistance to pyrimethamine and pfdhps 436A/F/H and 437G mutations associated with reduced susceptibility to sulfadoxine. In contrast mutations in codons 581G, and 613S in the pfdhps gene, and in pfmdr1, 86Y, 184Y, 1042D and 1246Y associated with resistance to amodiaquine, were less frequently observed. Importantly, pfdhfr I164L and pfdhps K540E mutations shown to be the most clinically relevant markers for high level clinical resistance to SP were not detected in Gabi. Conclusion Although parasites with genotypes associated with the highest levels of resistance to AQ + SP are not yet common in this setting, their importance for deployment of SMC and IPTp dictates that monitoring of these markers of resistance should accompany these interventions. This study also highlights the parasite heterogeneity within a small spatial area and the need to use caution when extrapolating results from surveys of molecular markers of resistance in a single site to inform regional policy decisions.