Challenges of assessing community mortality due to respiratory viruses in children aged less than 5 years

Background: Estimating the real impact of respiratory syncytial virus (RSV) disease is key for the development of vaccines and treatments. Ascertaining the burden of community mortality due to RSV is challenging due to the lack of primary data. Therefore, conducting observational studies to determine the factors associated with community mortality due to the virus in developing countries is important.Objective: Our aim in this study was to describe the obstacles, gaps, and challenges that investigators face in low-income, vulnerable regions in 4 developing countries on 3 continents.Results: The main obstacles and challenges of ascertaining community mortality due to RSV were defining strategies to consent families for testing before burial, sampling individuals at the household level, supporting bereaved parents with different cultural and religious backgrounds, establishing tailored strategies for studies in challenging settings, and integrating RSV mortality data from nasopharyngeal samples.Conclusion: Detailed logistical planning based on population sociodemographic information, grief counseling, staff training, and a multidisciplinary approach with adequate laboratory infrastructure is critical to successful observational community-based RSV studies

Metagenomics reveals impact of geography and acute diarrheal disease on the Central Indian human gut microbiome

© 2020, © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. Background: The Central Indian gut microbiome remains grossly understudied. Herein, we sought to investigate the burden of antimicrobial resistance and diarrheal diseases, particularly Clostridioides difficile, in rural-agricultural and urban populations in Central India, where there is widespread unregulated antibiotic use. We utilized shotgun metagenomics to comprehensively characterize the bacterial and viral fractions of the gut microbiome and their encoded functions in 105 participants. Results: We observed distinct rural-urban differences in bacterial and viral populations, with geography exhibiting a greater influence than diarrheal status. Clostridioides difficile disease was more commonly observed in urban subjects, and their microbiomes were enriched in metabolic pathways relating to the metabolism of industrial compounds and genes encoding resistance to 3rd generation cephalosporins and carbapenems. By linking phages present in the microbiome to their bacterial hosts through CRISPR spacers, phage variation could be directly related to shifts in bacterial populations, with the auxiliary metabolic potential of rural-associated phages enriched for carbon and amino acid energy metabolism. Conclusions: We report distinct differences in antimicrobial resistance gene profiles, enrichment of metabolic pathways and phage composition between rural and urban populations, as well as a higher burden of Clostridioides difficile disease in the urban population. Our results reveal that geography is the key driver of variation in urban and rural Indian microbiomes, with acute diarrheal disease, including C. difficile disease exerting a lesser impact. Future studies will be required to understand the potential role of dietary, cultural, and genetic factors in contributing to microbiome differences between rural and urban populations

Mapping national information and communication technology (ICT) infrastructure to the requirements of potential digital health interventions in low- and middle-income countries

Background Digital health can support health care in low- and middle-income countries (LMICs) by overcoming problems of distance, poor infrastructure and the need to provide community practitioners with specialist support. We used five RESPIRE countries as exemplars (Bangladesh, India, Indonesia, Malaysia, Pakistan) to identify the digital health solutions that are valuable in their local setting, worked together with local clinicians and researchers to explore digital health policy, electricity/ICT infrastructure, and socio-cultural factors influencing users’ ability to access, adopt and utilise digital health. Methods We adopted the Joanna Briggs Institute’s scoping review protocol and followed the Cochrane Rapid Review method to accelerate the review process, using the Implementation and Operation of Mobile Health projects framework and The Extended Technology Acceptance Model of Mobile Telephony to categorise the results. We conducted the review in four stages: (1) establishing value, (2) identifying digital health policy, (3) searching for evidence of infrastructure, design, and end-user adoption, (4) local input to interpret relevance and adoption factors. We used open-source national/international statistics such as the World Health Organization, International Telecommunication Union, Groupe Speciale Mobile, and local news/articles/government statistics to scope the current status, and systematically searched five databases for locally relevant exemplars. Results We found 118 studies (2015-2021) and 114 supplementary online news articles and national statistics. Digital health policy was available in all countries, but scarce skilled labour, lack of legislation/interoperability support, and interrupted electricity and internet services were limitations. Older patients, women and those living in rural areas were least likely to have access to ICT infrastructure. Renewable energy has potential in enabling digital health care. Low usage mobile data and voice service packages are relatively affordable options for mHealth in the five countries. Conclusions Effective implementation of digital health technologies requires a supportive policy, stable electricity infrastructures, affordable mobile internet service, and good understanding of the socio-economic context in order to tailor the intervention such that it functional, accessible, feasible, user-friendly and trusted by the target users. We suggest a checklist of contextual factors that developers of digital health initiatives in LMICs should consider at an early stage in the development process

Metagenomics Reveals Impact of Geography and Acute Diarrhoeal Disease on the Central Indian Human Gut Microbiome

Background: The Central Indian gut microbiome remains grossly understudied. Herein, we sought to investigate the burden of antimicrobial resistance and diarrhoeal diseases, particularly Clostridioides difficile, in rural-agricultural and urban populations in Central India, where there is widespread unregulated antibiotic use. We utilised shotgun metagenomics to comprehensively characterise the bacterial and viral fractions of the gut microbiome and their encoded functions in 105 participants. Results: We observed distinct rural-urban differences in bacterial and viral populations, with geography exhibiting a greater influence than diarrhoeal status. Clostridioides difficile disease was more commonly observed in urban subjects, and their microbiomes were enriched in metabolic pathways relating to the metabolism of industrial compounds and genes encoding resistance to 3rd generation cephalosporins and carbapenems. By linking phages present in the microbiome to their bacterial hosts through CRISPR spacers, phage variation could be directly related to shifts in bacterial populations, with the auxiliary metabolic potential of rural-associated phages enriched for carbon and amino acid energy metabolism.Conclusions: We report distinct differences in antimicrobial resistance gene profiles, enrichment of metabolic pathways and phage composition between rural and urban populations, as well as a higher burden of Clostridioides difficile disease in the urban population. Our results reveal that geography is the key driver of variation in urban and rural Indian microbiomes, with acute diarrhoeal disease, including C. difficile disease exerting a lesser impact. Future studies will be required to understand the potential role of dietary, cultural and genetic factors in contributing to microbiome differences between rural and urban populations

Global respiratory syncytial virus–related infant community deaths

BACKGROUND : Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. METHODS : The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. RESULTS : We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). CONCLUSIONS : We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines.The Bill & Melinda Gates Foundation.am2023Medical Virolog

Global Respiratory Syncytial Virus-Related Infant Community Deaths.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. METHODS: The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. RESULTS: We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8-3.3) was lower than in-hospital (2.4 months; IQR: 1.5-4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). CONCLUSIONS: We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines

Global respiratory syncytial virus–related infant community deaths

Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines

Mapping of Local Therapeutic Foods (LTF) and Micronutrients (MN); their logistics in community-based management of Severe Malnutrition (SAM, SUW) as a benchmark in tribal Melghat, Maharashtra

Background/Introduction: WHO recommended &lsquo;ready to use therapeutic food&rsquo; (RUTF) for community-based management (CMAM) of severely malnourished children (SMC). This is often rejected by children. The objective is to identify and map the locally produced and socio-culturally acceptable food items to treat SMC.&nbsp;Methods: Through community participation, eight varieties of MAHAN Local therapeutic foods (LTFs) were prepared by tribal females at our center as per WHO norms with a shelf life of 4 weeks. LTFs with micronutrients were given at the feeding centers in the villages under supervision 3 - 4 times a day.&nbsp;Results: Multiple, palatable, culturally acceptable, safe, feasible with local womanpower, and cost-effective recipes were developed. Hence, our LTFs are qualitatively superior to other therapeutic foods. This mapping exercise provides a ready reference to other government or non-government organizations for CMAM.&nbsp;Conclusion: MAHAN-LTF is a multiple, palatable, generalizable, and sustainable therapeutic food and are being used in other tribal blocks of India

Verbal autopsy to assess causes of mortality among the economically productive age group in the tribal region of Melghat, central India

Background & Objectives: Verbal autopsy (VA) is the systematic and retrospective inquiry (from relatives) about the symptoms of an illness prior to death. In tribal India, 67-75 per cent of deaths occur at home with an unknown cause of death (CoD). Hence, the aim of this study was to determine the CoD in the 16-60 yr age group utilizing VA. Methods: A prospective, community based longitudinal study was conducted in 32 tribal villages in the Melghat region of Maharashtra, between 2004 and 2020. Number of deaths and VAs in 16-60 yr age group were collected by village health workers (VHWs) and supervisors, verified by five different persons (internal-external) and cross-checked by three VA interpretation trained physicians. A modified version of WHO VA was used. Cause-specific mortality fractions were calculated. Results: Of the 1011 deaths recorded, mortality in males was significantly higher than females (P<0.001). A total of 763 VAs were conducted which revealed that tuberculosis was the leading CoD, followed by jaundice, heart diseases, diarrhoea, central nervous system infections and suicide. Suicides were significantly more common among males than in females (P=0.046). Significantly, more deaths occurred during the monsoon (P=0.002), especially diarrhoeal deaths (P=0.024). Interpretation & conclusions: The findings of this study suggest that, in Indian tribal areas, infectious diseases are the leading causes of morbidity and one of the major causes of deaths in economically productive age group. Intensified VHW-mediated interventions are required to reduce the premature deaths

Effect of home-based childcare on childhood mortality in rural Maharashtra, India: a cluster randomised controlled trial

Background Melghat, an impoverished rural area in Maharashtra state, India; has scarce hospital services and low health-seeking behaviour. At baseline (2004) the under-five mortality rate (U5MR) (number of deaths in children aged 0–5 years/1000 live births) was 147.21 and infant mortality rate (IMR) (number of deaths of infants aged under 1 year/1000 live births) was 106.6 per 1000 live births. We aimed at reducing mortality rates through home-based child care (HBCC) using village health workers (VHWs).Methods A cluster-randomised control trial was conducted in 34 randomly assigned clusters/villages of Melghat, Maharashtra state, between 2004 and 2009. Participants included all under-five children and their parents. Interventions delivered through VHWs were patient–public involvement, newborn care, disease management and behaviour change communications. Primary outcome indicators were U5MR and IMR. Secondary outcome indicators were neonatal mortality rate (NMR) (number of neonatal deaths aged 0–28 days/1000 live births) and perinatal mortality rate (PMR) (number of stillbirths and early neonatal deaths/1000 total births). Analysis was by intention-to-treat at the individual level. This trial was extended to a service phase (2010–2015) in both arms and a government replication phase (2016–2019) only for the intervention clusters/areas (IA).Findings There were 18 control areas/clusters (CA) allocated and analysed with 4426 individuals, and 16 of 18 allocated IA, analysed with 3230 individuals. The IMR and U5MR in IA were reduced from 106.60 and 147.21 to 32.75 and 50.38 (reduction by 69.28% and 65.78%, respectively) compared with increases in CA from 67.67 and 105.3 to 86.83 and 122.8, respectively, from baseline to end of intervention. NMR and PMR in IA showed reductions from 50.76 to 22.67 (by 55.34%) and from 75.06 to 24.94 (by 66.77%) respectively. These gains extended to villages in the service and replication phases.Interpretation This socio-culturally contextualised model for HBCC through VHWs backed up with institutional support is effective for significant reduction of U5MR, IMR and NMR in impoverished rural areas. This reduction was maintained in the study area during the service phase, indicating feasibility of implementation in large-scale public health programmes. Replicability of the model was demonstrated by a linear decline in all the mortality rates in 20 new villages during the government phase.Trial registration number NCT02473796