SummaryBackgroundMore than 500 000 neonatal deaths per year result from possible serious bacterial infections (pSBIs), but the causes are largely unknown. We investigated the incidence of community-acquired infections caused by specific organisms among neonates in south Asia.MethodsFrom 2011 to 2014, we identified babies through population-based pregnancy surveillance at five sites in Bangladesh, India, and Pakistan. Babies were visited at home by community health workers up to ten times from age 0 to 59 days. Illness meeting the WHO definition of pSBI and randomly selected healthy babies were referred to study physicians. The primary objective was to estimate proportions of specific infectious causes by blood culture and Custom TaqMan Array Cards molecular assay (Thermo Fisher, Bartlesville, OK, USA) of blood and respiratory samples.Findings6022 pSBI episodes were identified among 63 114 babies (95·4 per 1000 livebirths). Causes were attributed in 28% of episodes (16% bacterial and 12% viral). Mean incidence of bacterial infections was 13·2 (95% credible interval [CrI] 11·2–15·6) per 1000 livebirths and of viral infections was 10·1 (9·4–11·6) per 1000 livebirths. The leading pathogen was respiratory syncytial virus (5·4, 95% CrI 4·8–6·3 episodes per 1000 livebirths), followed by Ureaplasma spp (2·4, 1·6–3·2 episodes per 1000 livebirths). Among babies who died, causes were attributed to 46% of pSBI episodes, among which 92% were bacterial. 85 (83%) of 102 blood culture isolates were susceptible to penicillin, ampicillin, gentamicin, or a combination of these drugs.InterpretationNon-attribution of a cause in a high proportion of patients suggests that a substantial proportion of pSBI episodes might not have been due to infection. The predominance of bacterial causes among babies who died, however, indicates that appropriate prevention measures and management could substantially affect neonatal mortality. Susceptibility of bacterial isolates to first-line antibiotics emphasises the need for prudent and limited use of newer-generation antibiotics. Furthermore, the predominance of atypical bacteria we found and high incidence of respiratory syncytial virus indicated that changes in management strategies for treatment and prevention are needed. Given the burden of disease, prevention of respiratory syncytial virus would have a notable effect on the overall health system and achievement of Sustainable Development Goal.FundingBill & Melinda Gates Foundation

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NCT01533818.

Background Great disparities in immunization coverage exist in Pakistan between urban and rural areas. However, coverage estimates for large peri-urban slums in Sindh are largely unknown and implementation challenges remain unexplored. This study explores key supply- and demand-side immunization barriers in peri-urban slums, as well as strategies to address them. It also assesses immunization coverage in the target slums. Methods Conducted in four peri-urban slums in Karachi, this mixed-methods study consists of a baseline cross-sectional coverage survey of a representative sample of 840 caregivers of children aged 12–23 months, and 155 in-depth interviews (IDIs) through purposive sampling of respondents (caregivers, community influencers and immunization staff). After identifying the barriers, a further six IDIs were then conducted with immunization policy-makers and policy influencers to determine strategies to address these barriers, resulting in the development of an original validated implementation framework for immunization in peri-urban slums. A thematic analysis approach was applied to qualitative data. Results The survey revealed 49% of children were fully vaccinated, 43% were partially vaccinated and 8% were unvaccinated. Demand-side immunization barriers included household barriers, lack of knowledge and awareness, misconceptions and fears regarding vaccines and social and religious barriers. Supply-side barriers included underperformance of staff, inefficient utilization of funds, unreliable immunization and household data and interference of polio campaigns with immunization. The implementation framework’s policy recommendations to address these barriers include: (1) improved human resource management; (2) staff training on counselling; (3) re-allocation of funds towards incentives, outreach, salaries and infrastructure; (4) a digital platform integrating birth registry and vaccination tracking systems for monitoring and reporting by frontline staff; (5) use of digital platform for immunization targets and generating dose reminders; and (6) mutual sharing of resources and data between the immunization, Lady Health Worker and polio programmes for improved coverage. Conclusions The implementation framework is underpinned by the study of uncharted immunization barriers in complex peri-urban slums, and can be used by implementers in Pakistan and other developing countries to improve immunization programmes in limited-resource settings, with possible application at a larger scale. In particular, a digital platform integrating vaccination tracking and birth registry data can be expanded for nationwide use.

ANISA offers lessons for successful implementation of complex study protocols in areas of high child mortality and challenging social environments.