Causes and incidence of community-acquired serious infections among young children in south Asia (ANISA): an observational cohort study.

BACKGROUND: More 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. METHODS: From 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. FINDINGS: 6022 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. INTERPRETATION: Non-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. FUNDING: Bill & Melinda Gates Foundation.

Impact of involvement of non-formal health providers on TB case notification among migrant slum-dwelling populations in Odisha, India.

BACKGROUND: Migrant labourers living in the slums of urban and industrial patches across India make up a key sub-population so far controlling Tuberculosis (TB) in the country is concerned. This is because many TB patients from these communities- remain under reached by the Revised National Tuberculosis Control Programme (RNTCP) of India. This marginalized community usually seeks early-stage healthcare from "friendly neighbourhood" non-formal health providers (NFHPs). Because, RNTCP has limited capacity to involve the NFHPs, an implementation research project was conceived, whereby an external partner would engage with the NFHPs to enable them to identify early TB symptomatics from this key sub-population who would be then tested using Xpert MTB/RIF technology. Diagnosed TB cases among them would be referred promptly to RNTCP for treatment. This paper aimed to describe the project and its impact. METHODS: Adopting a quasi-experimental before-after design, four RNTCP units from two major urban-industrial areas of Odisha were selected for intervention, which spanned five quarters and covered 151,400 people, of which 30% were slum-dwelling migrants. Two similar units comprised the control population. The hypothesis was, reaching the under reached in the intervention area through NFHPs would increase TB notification from these traditionally under-notifying units. RNTCP notification data during intervention was compared with pre-intervention era, adjusted for contemporaneous changes in control population. RESULTS: The project detected 488 Xpert+ TB cases, of whom 466 were administered RNTCP treatment. This translated into notification of additional 198 new bacteriologically positive cases to RNTCP, a 30% notification surge, after adjustment for 2% decline in control. This meant an average quarterly increase in notification of 41.20(20.08, 62.31; p<0.001) cases. The increase was immediate, evident from the rise in level in the time series analysis by 50.42(10.28, 90.55; p = 0.02) cases. CONCLUSION: Engagement with NFHPs contributed to an increase in TB notification to RNTCP from key under reached, slum-dwelling migrant populations.

Challenges in Implementation of the ANISA Protocol at the Odisha Site in India.

BACKGROUND: The Aetiology of Neonatal Infection in South Asia (ANISA) study is being carried out at 5 sites across Bangladesh, India and Pakistan, generating in-depth information on etiologic agents in the community setting. Pregnancies are identified, births are registered and young infants are followed up to 59 days old with regular assessments for possible serious bacterial infection following a generic protocol. Specimens are collected from suspected cases. This article describes the challenges in implementing the generic ANISA protocol and modifications made to accommodate the Odisha site, India. CHALLENGES: Primary challenges in implementing the protocol are the large geographic area, with a population of over 350,000, to be covered; assessing young infants at home and arranging timely transport of sick young infants to study hospitals for physician confirmation of illness; and specimen collection and treatment. A large workforce is deployed in a 3-tier system in the field, while clinical, microbiology, laboratory and data management teams collaborate dynamically. Mobile phones with text message capability, integration with the Odisha State government's health system, involvement of local communities and strict monitoring at different levels have been critical in addressing these challenges. CONCLUSION: This article describes the challenges and modalities adopted to collect complex and accurate data on etiology, timing of disease and associated factors for community-acquired neonatal infections. Attention to local culture and customs, training and employing community level workers and supervisors, involving existing government machinery, using technology (cell phones), and uninterrupted systematic monitoring are critical for implementing such complex protocols that aim to collect population-based data to drive policy.

Infection Surveillance Protocol for a Multicountry Population-based Study in South Asia to Determine the Incidence, Etiology and Risk Factors for Infections Among Young Infants of 0 to 59 Days Old.

BACKGROUND: Insufficient knowledge of the etiology and risk factors for community-acquired neonatal infection in low-income countries is a barrier to designing appropriate intervention strategies for these settings to reduce the burden and treatment of young infant infection. To address these gaps, we are conducting the Aetiology of Neonatal Infection in South Asia (ANISA) study among young infants in Bangladesh, India and Pakistan. The objectives of ANISA are to establish a comprehensive surveillance system for registering newborns in study catchment areas and collecting data on bacterial and viral etiology and associated risk factors for infections among young infants aged 0-59 days. METHODS: We are conducting active surveillance in 1 peri-urban and 4 rural communities. During 2 years of surveillance, we expect to enroll an estimated 66,000 newborns within 7 days of their birth and to follow-up them until 59 days of age. Community health workers visit each young infant in the study area 3 times in the first week of life and once a week thereafter. During these visits, community health workers assess the newborns using a clinical algorithm and refer young infants with signs of suspected infection to health care facilities where study physicians reassess them and provide care if needed. On physician confirmation of suspected infection, blood and respiratory specimens are collected and tested to identify the etiologic agent. CONCLUSIONS: ANISA is one of the largest initiatives ever undertaken to understand the etiology of young infant infection in low-income countries. The data generated from this surveillance will help guide evidence-based decision making to improve health care in similar settings.