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

Background Long-term care facilities (LTCFs) are vulnerable to outbreaks of coronavirus disease 2019 (COVID-19). Timely epidemiological surveillance is essential for outbreak response, but is complicated by a high proportion of silent (non-symptomatic) infections and limited testing resources. Methods We used a stochastic, individual-based model to simulate transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along detailed inter-individual contact networks describing patient-staff interactions in a real LTCF setting. We simulated distribution of nasopharyngeal swabs and reverse transcriptase polymerase chain reaction (RT-PCR) tests using clinical and demographic indications and evaluated the efficacy and resource-efficiency of a range of surveillance strategies, including group testing (sample pooling) and testing cascades, which couple (i) testing for multiple indications (symptoms, admission) with (ii) random daily testing. Results In the baseline scenario, randomly introducing a silent SARS-CoV-2 infection into a 170-bed LTCF led to large outbreaks, with a cumulative 86 (95% uncertainty interval 6–224) infections after 3 weeks of unmitigated transmission. Efficacy of symptom-based screening was limited by lags to symptom onset and silent asymptomatic and pre-symptomatic transmission. Across scenarios, testing upon admission detected just 34–66% of patients infected upon LTCF entry, and also missed potential introductions from staff. Random daily testing was more effective when targeting patients than staff, but was overall an inefficient use of limited resources. At high testing capacity (> 10 tests/100 beds/day), cascades were most effective, with a 19–36% probability of detecting outbreaks prior to any nosocomial transmission, and 26–46% prior to first onset of COVID-19 symptoms. Conversely, at low capacity (< 2 tests/100 beds/day), group testing strategies detected outbreaks earliest. Pooling randomly selected patients in a daily group test was most likely to detect outbreaks prior to first symptom onset (16–27%), while pooling patients and staff expressing any COVID-like symptoms was the most efficient means to improve surveillance given resource limitations, compared to the reference requiring only 6–9 additional tests and 11–28 additional swabs to detect outbreaks 1–6 days earlier, prior to an additional 11–22 infections. Conclusions COVID-19 surveillance is challenged by delayed or absent clinical symptoms and imperfect diagnostic sensitivity of standard RT-PCR tests. In our analysis, group testing was the most effective and efficient COVID-19 surveillance strategy for resource-limited LTCFs. Testing cascades were even more effective given ample testing resources. Increasing testing capacity and updating surveillance protocols accordingly could facilitate earlier detection of emerging outbreaks, informing a need for urgent intervention in settings with ongoing nosocomial transmission.

According to the current World Health Organization guidelines, the drug prevention of malaria during pregnancy does not adequately cover the first trimester of gestation in high-transmission areas. Although the pathophysiological mechanisms of early infections are not completely understood yet, a review of the most recent studies on the topic suggests that their consequences are serious in terms of maternal anemia and low birth weight. Consequently, there is a need to focus on the awareness of women in a period hard to access, to develop safe drugs to be used in the first trimester, and to consider preconceptional interventions in teenage girls, such as a new malaria vaccine to be used in pregnancy.

Early neonatal infections caused by extended-spectrum-beta-lactamase-producing Enterobacterales (ESBL-PE) are prevalent in low- and middle-income countries, posing significant treatment challenges. This study investigates ESBL-PE colonization in 499 mother-neonate pairs from Madagascar and Cambodia, with stool samples collected at delivery and from neonates during the first three days of life. Using short- and long-read sequencing, identical isolates or plasmids are detected within each pair to assess neonatal acquisition from maternal source. Associated risk factors are identified through multinomial regression. Maternal gut carriage accounts for only 16.5% of neonatal ESBL-PE acquisition, suggesting that most cases originate from other sources. Primiparity and the wet season are associated with an increased risk of acquisition from the mother, while cesarean delivery, neonatal resuscitation, and wet season are associated with acquisition from other sources. These findings challenge the paradigm that maternal carriage is the primary source of early neonatal ESBL-PE colonization, highlighting the need for further research into alternative sources to inform targeted interventions. Among mother-neonate pairs in Madagascar and Cambodia, authors found maternal gut carriage explains only 16.5% of early neonatal extended-spectrum beta-lactamase Enterobacterales acquisition, questioning its role as the main source of colonization.

Background. Few studies have evaluated the effect of malaria on intrauterine growth restriction on the basis of the fetal growth rate, rather than just the small-for-gestational age z score. Here, we assessed the impact of malaria on IUGR, using data from a longitudinal, ultrasonography-based follow-up study of Beninese women. Methods. A total of 1016 women were followed up from gestational week 17 to delivery. Malaria was detected every month. Women underwent ultrasonography 4 times for gestational age determination and fetal biometry. We assessed the effect of malaria on birth weight-for-gestational age z score (n = 735 women) and fetal growth velocity (n = 664), defined as a change in fetal weight z score over time. Results. Malaria was detected in 43% of women. Fetal growth velocity was negative overall, decreasing further at the end of the third trimester. Women with ≥2 malarial parasite infections tended to have lower z scores than uninfected women. Malaria both in early and late pregnancy was associated with a reduction in fetal growth velocity, which occurred either immediately or with a delay after infection. Discussions. We confirmed the deleterious effect of malaria during both early and late pregnancy on fetal growth. This stresses the importance of starting preventive measures against malaria as early as possible during pregnancy.

Background Non-pharmaceutical measures such as lockdowns, curfews and place closures were implemented in France during 2020–2022 to reduce contacts in the population, to limit the spread of SARS-CoV-2 and reduce COVID-19 healthcare burden. Individuals also changed their behaviours as a response to the pandemic. Here, we present the results of the SocialCov survey that characterise the evolution of contacts in France between December 2020 and May 2022 to better understand the short and long term impact of these interventions on social mixing. Methods A questionnaire was advertised over six independent communication campaigns through the governmental application TousAntiCovid between December 2020 and June 2022. Participants were asked to detail social contacts in the previous day, including contact age, location, duration and type (physical/conversational). Results Over the six distinct campaigns, 44,396 individuals participated in the survey, declaring 300,735 contacts in total. The patterns of contacts strongly evolved over time, along with the progressive easing of national mitigation measures. The number of contacts in the French population increased from 5.3 contacts per day on average in December 2020 to 9.7 in May 2022. Mixing patterns were affected by age of participants, holidays and weekends. Healthcare workers declared 18.4 contacts on average during working days, roughly twice more than other workers. Reported risk perception changed throughout the two year period. Conclusions Results provide a detailed picture of contact evolution over the years 2020–2022 in France. In addition to a major evolution of contact density over time, this study highlights strong heterogeneities in contact patterns according to age, employment and weekend/vacation periods. The contact matrices provided here can be used to inform age-stratified transmission models of respiratory pathogens in the context of implementation of multiple non-pharmaceutical measures.

In low and middle income countries (LMICs), where the burden of neonatal sepsis is the highest, the spread of extended spectrum beta-lactamase-producing enterobacteriaceae (ESBL-PE) in the community, potentially contributing to the neonatal mortality, is a public health concern. Data regarding the acquisition of ESBL-PE during the neonatal period are scarce. The routes of transmission are not well defined and particularly the possible key role played by pregnant women. This study aimed to understand the neonatal acquisition of ESBL-PE in the community in Madagascar. The study was conducted in urban and semi-rural areas. Newborns were included at birth and followed-up during their first month of life. Maternal stool samples at delivery and six stool samples in each infant were collected to screen for ESBL-PE. A Cox proportional hazards model was performed to identify factors associated with the first ESBL-PE acquisition. The incidence rate of ESBL-PE acquisition was 10.4 cases/1000 newborn-days [95% CI: 8.0-13.4 cases per 1000 newborn-days]. Of the 83 ESBL-PE isolates identified, Escherichia coli was the most frequent species (n = 28, 34.1%), followed by Klebsiella pneumoniae (n = 20, 24.4%). Cox multivariate analysis showed that independent risk factors for ESBL-PE acquisition were low birth weight (adjusted Hazard-ratio (aHR) = 2.7, 95% CI [1.2; 5.9]), cesarean-section, (aHR = 3.4, 95% CI [1.7; 7.1]) and maternal use of antibiotics at delivery (aHR = 2.2, 95% CI [1.1; 4.5]). Our results confirm that mothers play a significant role in the neonatal acquisition of ESBL-PE. In LMICs, public health interventions during pregnancy should be reinforced to avoid unnecessary caesarean section, unnecessary antibiotic use at delivery and low birth weight newborns.

Background Bacterial vaginosis (BV) is associated with a higher risk of preterm delivery and spontaneous abortion. Yet little data on BV prevalence exist for sub-Saharan countries. The aim of this study was to estimate the prevalence of bacterial vaginosis and associated risk factors among pregnant women in Senegal. Methods From October 2013 to December 2018, pregnant women in their third trimester were recruited in two primary health centers (one suburban, one rural) in Senegal. Healthcare workers interviewed women and collected a lower vaginal swab and a blood sample. Vaginal flora were classified into four categories using vaginal smear microscopic examination and Gram’s coloration. In our study, BV was defined as vaginal flora with no Lactobacillus spp. Variables associated with BV were analyzed using STATA® through univariate and multivariate analysis. Results A total of 457 women provided a vaginal sample for analysis. Overall, BV prevalence was 18.6% (85/457) [95% CI 15.4–22.6]) and was similar in suburban and rural areas (18.9% versus 18.1%, p = 0.843). Multivariate analysis showed that primigravidity was the only factor independently associated with a lower risk of BV (aOR 0.35 [95% CI 0.17–0.72]). Conclusions Our study showed significant BV prevalence among pregnant women in Senegal. Although the literature has underscored the potential consequences of BV for obstetric outcomes, data are scarce on BV prevalence in sub-Saharan African countries. Before authorities consider systematic BV screening for pregnant women, a larger study would be useful in documenting prevalence, risk factors and the impact of BV on pregnancy outcomes.

Background Recent data on sexually transmitted infections (STIs) and bacterial vaginosis (BV) in the general population of Madagascar is scarce. Our objective is to estimate the Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), and BV prevalence among women and to determine associated risk factors. Methods We recruited women aged 18–45 years consulting at a hospital in Antananarivo in a cross-sectional study. We collected socio-demographic and behavioral data. Vaginal swabs were collected for each individual. STIs were detected by qPCR and BV using the Nugent score. We explored factors associated with having an STI using logistic regressions. Results Of the 501 recruited women, 242 (48%) were married. Only one woman in three ever used condoms. The prevalence of CT was 11.8% (95% Confidence Interval: 9.0, 14.6), NG: 4.2% (2.4, 5.9), TV: 14.8% (11.7, 17.9), MG: 8.2% (5.8, 10.6), and BV: 39.6% (35.3, 43.9). Factors associated with an STI were having sex in exchange for favors (adjusted Odds Ratio (aOR): 4.25, 95%CI: 1.27, 16.6), BV (aOR: 2.14, 95%CI: 1.34, 3.47) or intermediate vaginal microbiota (aOR: 2.10, 95%CI: 1.19, 3.72), and being in a non-marital relationship compared to married (aOR: 1.86, 95%CI: 1.16, 2.98). Conclusions To address the high prevalence of STIs, prevention programs should target women who are more likely to engage in sex in exchange for favors and empower them with negotiation skills on condom use. Given the elevated prevalence of dysbiosis and its association with STIs, it is crucial to prioritize research efforts toward a comprehensive understanding of this relationship.

The transmission risk of SARS-CoV-2 within hospitals can exceed that in the general community because of more frequent close proximity interactions (CPIs). However, epidemic risk across wards is still poorly described. We measured CPIs directly using wearable sensors given to all present in a clinical ward over a 36-h period, across 15 wards in three hospitals in April-June 2020. Data were collected from 2114 participants and combined with a simple transmission model describing the arrival of a single index case to the ward to estimate the risk of an outbreak. Estimated epidemic risk ranged four-fold, from 0.12 secondary infections per day in an adult emergency to 0.49 per day in general paediatrics. The risk presented by an index case in a patient varied 20-fold across wards. Using simulation, we assessed the potential impact on outbreak risk of targeting the most connected individuals for prevention. We found that targeting those with the highest cumulative contact hours was most impactful (20% reduction for 5% of the population targeted), and on average resources were better spent targeting patients. This study reveals patterns of interactions between individuals in hospital during a pandemic and opens new routes for research into airborne nosocomial risk.