Antimicrobial resistance in neonatal sepsis is rising, yet mechanisms of resistance that often spread between species via mobile genetic elements, ultimately limiting treatments in low- and middle-income countries (LMICs), are poorly characterized. The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network was initiated to characterize the cause and burden of antimicrobial resistance in neonatal sepsis for seven LMICs in Africa and South Asia. A total of 36,285 neonates were enrolled in the BARNARDS study between November 2015 and December 2017, of whom 2,483 were diagnosed with culture-confirmed sepsis. Klebsiella pneumoniae (n = 258) was the main cause of neonatal sepsis, with Serratia marcescens (n = 151), Klebsiella michiganensis (n = 117), Escherichia coli (n = 75) and Enterobacter cloacae complex (n = 57) also detected. We present whole-genome sequencing, antimicrobial susceptibility and clinical data for 916 out of 1,038 neonatal sepsis isolates (97 isolates were not recovered from initial isolation at local sites). Enterobacterales (K. pneumoniae, E. coli and E. cloacae) harboured multiple cephalosporin and carbapenem resistance genes. All isolated pathogens were resistant to multiple antibiotic classes, including those used to treat neonatal sepsis. Intraspecies diversity of K. pneumoniae and E. coli indicated that multiple antibiotic-resistant lineages cause neonatal sepsis. Our results will underpin research towards better treatments for neonatal sepsis in LMICs.
Summary
Background
Podoconiosis is a type of tropical lymphoedema that causes massive swelling of the lower limbs. The disease is associated with both economic insecurity, due to long-term morbidity-related loss of productivity, and intense social stigma. Reliable and detailed data on the prevalence and distribution of podoconiosis are scarce. We aimed to fill this data gap by doing a nationwide community-based study to estimate the number of cases throughout Rwanda.
Methods
We did a population-based cross-sectional survey to determine the national prevalence of podoconiosis. A podoconiosis case was defined as a person with bilateral, asymmetrical lymphoedema of the lower limb present for more than 1 year, who tested negative for
Wuchereria bancrofti
antigen (determined by Filariasis Test Strip) and specific IgG4 (determined by Wb123 test), and had a history of any of the associated clinical signs and symptoms. All adults (aged ≥15 years) who resided in any of the 30 districts of Rwanda for 10 or more years were invited at the household level to participate. Participants were interviewed and given a physical examination before Filariasis Test Strip and Wb123 testing. We fitted a binomial mixed model combining the site-level podoconiosis prevalence with continuous environmental covariates to estimate prevalence at unsampled locations. We report estimates of cases by district combining our mean predicted prevalence and a contemporary gridded map of estimated population density.
Findings
Between June 12, and July 28, 2017, 1 360 612 individuals—719 730 (53%) women and 640 882 (47%) men—were screened from 80 clusters in 30 districts across Rwanda. 1143 individuals with lymphoedema were identified, of whom 914 (80%) had confirmed podoconiosis, based on the standardised diagnostic algorithm. The overall prevalence of podoconiosis was 68·5 per 100 000 people (95% CI 41·0–109·7). Podoconiosis was found to be widespread in Rwanda. District-level prevalence ranged from 28·3 per 100 000 people (16·8–45·5, Nyarugenge, Kigali province) to 119·2 per 100 000 people (59·9–216·2, Nyamasheke, West province). Prevalence was highest in districts in the North and West provinces: Nyamasheke, Rusizi, Musanze, Nyabihu, Nyaruguru, Burera, and Rubavu. We estimate that 6429 (95% CI 3938–10 088) people live with podoconiosis across Rwanda.
Interpretation
Despite relatively low prevalence, podoconiosis is widely distributed geographically throughout Rwanda. Many patients are likely to be undiagnosed and morbidity management is scarce. Targeted interventions through a well coordinated health system response are needed to manage those affected. Our findings should inform national level planning, monitoring, and implementation of interventions.
Funding
Wellcome Trust.
Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin-gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis.Methods In BARNARDS, consenting mother-neonates aged 0-60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in
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