Individuals with African ancestry have extensive genomic diversity but have been underrepresented in genomic research. There is also extensive global diversity in the exposome  which should be considered for integrative genomic and environmental health research in Africa. To address current research gaps, we organized a workshop on environmental health research in Africa in conjunction with the H3Africa Consortium and the African Society of Human Genetics meetings in Kigali, Rwanda. The workshop was open to all researchers with an interest in environmental health in Africa and involved presentations from experts within and outside of the Consortium. This workshop highlighted innovative research occurring on the African continent related to environmental health and the interplay between the environment and the human genome. Stories of success, challenges, and collaborative opportunities were discussed through presentations, breakout sessions, poster presentations, and a panel discussion. The workshop informed participants about environmental risk factors that can be incorporated into current or future epidemiology studies and addressed research design considerations, biospecimen collection and storage, biomarkers for measuring chemical exposures, laboratory strategies, and statistical methodologies. Inclusion of environmental exposure measurements with genomic data, including but not limited to H3Africa projects, can offer a strong platform for building gene-environment (G x E) research in Africa. Opportunities to leverage existing resources and add environmental exposure data for ongoing and planned studies were discussed. Future directions include expanding the measurement of both genomic and exposomic risk factors and incorporating sophisticated statistical approaches for analyzing high dimensional G x E data. A better understanding of how environmental and genomic factors interact with nutrition and infection is also needed. Considering that the environment represents many modifiable risk factors, these research findings can inform intervention and prevention efforts towards improving global health. The work of this Consortium includes common diseases such as cardiovascular2, neurological3, respiratory4, kidney5, and other non-communicable diseases, as well as research in infectious diseases. Developments in pharmacogenomics6 and the human microbiome7 are underway, and many studies incorporate information about HIV, malaria, and tuberculosis. The Consortium also promotes opportunities for training in bioinformatics10, supports three biorepositories on the African continent, and facilitates policy development and guidelines with recommendations on ethical issues13.The Human Heredity and Health in Africa (H3Africa) initiative began as a joint effort of the National Institutes of Health (NIH) Common Fund Global Health Program and the Wellcome Trust, in partnership with the African Society of Human Genetics. H3Africa aims to support the establishment of a sustainable African research infrastructure for the study of the genetic and environmental contributors to disease and health16 within the H3Africa network. This enhancement would enable greater ability of ongoing H3Africa projects to evaluate both genomic, epigenomic, and environmental risk factors of disease in Africa. To support this effort, NIEHS facilitated a one-day workshop on environmental health entitled, “Environmental Health in Africa: Opportunities to Expand Research Capacity in the H3Africa Consortium.” The workshop was held one day prior to the 12th H3Africa Consortium meeting in Kigali, Rwanda, in September 2018. A total of seven speakers and five panelists were invited to lead the workshop, representing environmental health research expertise in the African setting. Scholarships enabled travel support for African-based pre- and post-doctoral trainees who presented posters. The workshop agenda, speaker biographies, poster abstracts, bibliography of recommended reading, and participant list can be found in theworkshop meeting book posted on themeeting website.Much of the work within the first phase of H3Africa (August 2012 – July 2017) focused on building genomic infrastructure, research networks, and training. Phase two of the program began in 2017 and involved co-funding from multiple NIH institutes, including the National Institute of Environmental Health Sciences (NIEHS), to include more coverage of environmental exposures in H3Africa projects. Several projects began to incorporate environmental exposures, but existing data, planned data, or suitable specimen collection around such exposures were limited in scope. A need was identified to incorporate more education, training, and research on environmental health or the exposomeThe workshop was opened by Dr. Gwen Collman, Director of the NIEHS Division of Extramural Research and Training. Dr. Collman described the long history of NIEHS-supported environmental health research in Africa and the unique exposures and health challenges. She described the commitment of NIEHS to global environmental health and involvement in the H3Africa consortium. Dr. Kim McAllister, Program Administrator at NIEHS, provided brief remarks on the charge of the workshop, on behalf of the NIEHS organizing team. She highlighted the opportunity for H3Africa projects to expand exploration for both genomic and environmental risk factors of complex diseases in Africa. The objectives of the workshop were to highlight current and innovative research occurring on the African continent related to the interplay between the environment and the human genome. The workshop was designed to enable face to face interactions between Consortium members and environmental health experts to facilitate collaborative opportunities and global networking. Sharing of expertise, research recommendations for study design, biospecimen collection and storage practices, and statistical methodologies were discussed, as well as the current research challenges and needs of existing H3Africa projects.To better understand the data and interests of existing H3Africa projects, a short survey including fifteen questions was sent to all H3Africa project PIs by the coordinating center, to collect information on environmental exposures in H3Africa projects. Data collected on questionnaires, biomarkers of environmental exposures, monitoring data, or related information was reported. Characteristics of the H3Africa project study populations were collected including life stage, location, important co-morbidities, key health outcomes, and current environmental data. The survey also asked about interests in collecting more environmental exposure data in existing study populations. Nine projects completed the survey prior to the workshop ;Table 1The study respondents reported needs for training in the areas of laboratory methods, bioinformatics, and statistical analysis of complex environmental exposures. The most common critical issues reported to enable more environmental health research were storage capacity and laboratory training. Improvements in the communication strategies with project sites, timing of specimen collection, better implementation of sample collection, and a better understanding of the relevance of additional exposures to measured outcomes were also noted. Overall, the surveys indicated substantial interest in learning more about environmental exposures and risk assessments in the H3Africa study populations, but limited data was currently in hand or planned for collection. Training and education for junior investigators and partnerships with expert laboratories outside of Africa were emphasized.The workshop presenters covered experimental design, exposures of interest, exposure measurements, biospecimen collection and storage, and laboratory and statistical methodologies. They also discussed training needs and other challenges, populations at risk, health outcomes of interest for represented populations, and collaborative opportunities. The scientific content of the presentations is organized here by exposure category.GEOHealth) Hub. He described the environmental exposures associated with informal e-waste recycling practices in West Africa . E-waste workers and neighboring communities are exposed to multiple toxic exposures related to recycling activities  of electronics in a highly concentrated area17. High levels of toxic metals  and persistent organic pollutants have been found in air, water, soil, and food samples on and near e-waste sites that far exceed United States Environmental Protection Agency (U.S. EPA) and World Health Organization (WHO) thresholds of safe exposure. The GEOHealth Hub project goals include: characterization of specific exposures derived from electronic waste recycling activities, assessment of biological markers of dose of exposure, and evaluation of health outcomes  associated with these exposures. Biological samples (blood and urine) were used to measure metals and flame retardants, polycyclic aromatic hydrocarbons (PAHs), and other organic compounds, and ambient and personal air monitoring were used to measure air pollution. Interactions between occupational exposures and other environmental exposures were also assessed through a detailed questionnaire. While the hub’s activities aim broadly to develop new methods for assessing exposure in the informal sector in the hope of developing effective and efficient interventions that reduce the exposures, ongoing analyses have been expanded to include investigation of associations between exposures in the e-waste dismantling industry and biologic effects as measured by the following molecular biology platforms: i) gene-expression profiling of epithelial cells from the oral cavity and nasal turbinate; ii) metabolomic profiling of plasma; and iii) methylation profiling of blood DNA. Preliminary results have found exceptionally high PM2.5 exposures for e-waste workers using personal air monitoring filters. Discussions following this presentation focused on the complexities of impacting better e-waste worker protections and informing government and city policies to improve workers’ lives. The investigators hope to explore pilot interventions to reduce exposures at the Agbogbloshie site in Ghana and scale-up studies in other West Africa countries in the future.The first presenter in the workshop was Dr. Julius Fobil from the University of Ghana, one of the principal investigators of the Michigan-West Africa Global Environmental and Occupational Health  attributed to household air pollution from solid particles and exposure to ambient particulate matter pollution ranking within the top 10 leading risk factors for DALY in 1990 and 201018. In the Eastern Africa GEOHealth Hub, air pollution exposure  was measured through air quality monitoring , questionnaires , and personal exposure monitoring  to assign household level exposures. Pictures and brief explanations of the technologies used for air pollution monitoring to measure PM2.5 were also shared . More details of the GEOHealth Hub study populations were described, including study sites, study protocols and staff training, and data was placed in context with the overall hub aims. Preliminary data such as descriptive statistics of the study populations were also shared. Overall, this presentation described the public health issue of air pollution in Eastern Africa, provided examples of measuring ambient air pollution in an African setting, and shared equipment and methodology recommendations with the workshop participants.Dr. Abera Kumie, from Addis Ababa University, presented recent findings from the Eastern Africa GEOHealth Hub studying ambient air pollution exposure and child respiratory health in Ethiopia, Uganda, Rwanda, and Kenya. Air pollution is an important global challenge resulting in 4.3 million deaths from indoor air pollution and 3.7 million deaths from outdoor/ambient air pollution each year . Air pollution poses a heavy burden in Eastern Africa, and Dr. Kumie noted exposure statistics for Ethiopia and sources of exposure, with a primary focus on PM2.5. Sources of air pollution were both mobile and stationary, with power generation, factories, and household biomass contributing significantly to substantial burdens of pollutants CO, NO19. These have included altering many postharvest processing practices for the groundnuts, including hand sorting of the nuts, sun drying nuts on natural fiber mats, storing food in natural fiber bags (rather than plastic or synthetic bags), and using insecticides in the storage facilities. Aflatoxin exposure is also associated with stunting (reduced growth in young children) and ongoing clinical trials  are exploring the seasonal effects of aflatoxin exposure on children’s growth and development.Dr. Joshua Smith, a post-doctoral fellow in Dr. John Groopman’s laboratory at Johns Hopkins University presented ongoing work associated with the translation of basic research to public health prevention related to mycotoxin exposures, which could serve as a model for other exposures. Mycotoxins, including aflatoxins, are secondary metabolites of fungi that are frequent contaminants of improperly stored food crops and are highly carcinogenic to the liver (and associated with increased liver cancer risk). Extensive mechanistic research over many years has enabled the identification of an aflatoxin B1-lysine adduct in serum using isotope-dilution liquid chromatography/tandem mass spectrometry as a highly effective biomarker for aflatoxin exposure. Multiple primary and secondary prevention mitigation strategies have been used to both reduce aflatoxin exposure with improved food storage methods and dietary changes and introduce chemopreventive interventions using broccoli sprouts, green tea, chlorophyllin, and other agents to induce hepatic detoxification and reduce aflatoxin absorption. Primary prevention strategies addressing the reduction of aflatoxin contamination of staple groundnut foods have been applied in Guinea, and these have successfully reduced aflatoxin exposure20. Although no cadmium or lead was found in water, these metals contaminated soils and house dust of women with elevated concentrations suggesting soil tracked indoors and part of house dust could represent an important source of cadmium and lead exposures. Concentrations of these metals were also higher on hand wipes of this geographic cluster, suggesting that inadvertent ingestion of contaminated house dust could be a potential route of exposure.Dr. Cathrine Hoyo from North Carolina State University presented on heavy metal exposure and cardiometabolic phenotypes. She shared results from her work in the Newborn Epigenetic Study (NEST) evaluating metals exposures and obesity in just over 310 children living in North Carolina, USA. Exposures discussed included cadmium and lead, which was found in the blood samples of pregnant women during the first trimester. Women with elevated cadmium and lead exposure were geographically clustered based on prenatal mailing addresses. This clustering in space of women with elevated levels of cadmium and lead was followed by sampling and measuring soil, house dust, and water to identify potential sources and routes of exposure and guide prevention effortsIARC) and Agency for Toxic Substances and Disease Registry (ATSDR), because: their industrial applications are numerous, they are poorly excreted , and they sizably contribute to cardiovascular and metabolic disease, which are diseases in the top ten global causes of mortality. While smoking is a major source of cadmium, it is estimated that non-smokers also ingest~1µg per day from diet as plants take up this compound from the air, contaminated soil, and water21. The European Union estimates that cadmium exposure will increase with the projected increase in the production of batteries for electric vehicles, for which cadmium is an important component21. The yet unexplained higher propensity for exposure among women will affect unborn children and their offspring for generations to come as observed with juvenile obesity22. In addition to key highlights to her research on the health effects of metals in children, Dr. Hoyo described considerations for biosample collection for investigators interested in studying metals. Notably, she described recent advances in Inductively Coupled Plasma-Mass Spectrometry that can be leveraged to identify multiple metals in limited specimens. She also described contamination issues that may arise when collecting samples, and methods to help obtain good data for these exposures.Cadmium and lead are in the top ten chemicals of concern by the International Agency for Research on Cancer , cyanogenic toxicants, and outbreaks of a motor system disease, known as konzo, in sub-Saharan Africa. The causes of konzo have largely remained unclear, and Dr. Tshala-Katumbay’s research is focusing on increasing the understanding of lifespan interactions between environmental stressors (toxicants), diet , and genetics in relation to motor system degeneration. These studies are exploring the biomarkers and toxicity mechanisms of cassava-associated motor/cognition deficits, testing a central hypothesis that genetic variations, along with epigenetics and microbiome variation, modulate risks for cassava-associated neurodegeneration. A key premise to these studies is that production of cyanate, a metabolite of cyanide , carbamylates lysine-enriched proteins to induce conformational changes and alters vital molecular functions including, possibly, transcription and cell signaling. Dr. Tshala-Katumbay’s project encompasses many scientific fields including plant-microbiota-host interactions, functional metagenomics, transgenerational epigenetics, and neuropathogenic patterns. He emphasized ongoing capacity building through the training and mentoring of young investigators in the Democratic Republic of the Congo through active participation in supervised field work, training in ethics and responsible conduct for research, field epidemiology, neurology, nutritional toxicology, and environmental health science.23. Chemicals used in IRS include DDT (dichlorodiphenyltrichloroethane) and pyrethroids, which may have endocrine disrupting effects in rodents and humans. Although IRS is effective in reducing mortality due to malaria, the potentially negative side effects of IRS have not been fully evaluated. Dr Chevrier described the interesting history of pyrethroids including their source and initial development in the early 1800s, the active structure identification in 1920, the generation of the synthetic product in 1960-70, and widespread generation for use in the insecticide market beginning in 1986. Pyrethroids are projected to represent a $6 billion industry by 2021. Distribution of pyrethroids use for IRS around the world was also described in detail, including the WHO-reported use of alpha-Cypermethrin, Deltamethrin, lambda-Cyhalothrin, and Cyfluthrin in 2015. The history of DDT was also briefly summarized, beginning with the initial discovery in 1939, recognition for Paul Müller’s DDT discovery in 1948 (Nobel Prize), the 1962 publication of the bookSilent Spring by Rachel Carson warning of harmful effects to DDT-exposed wildlife, the 1970s banning of DDT in Western Countries, the 2001 Stockholm Convention on Persistent Organic Pollutants, and the 2006 WHO recommendation of IRS upscaling to combat malaria. Persistence, distribution in the body, excretion, and related characteristics of DDT and pyrethroids and their metabolites and known toxicities were presented.Dr. Jonathan Chevrier, from McGill University, presented on Indoor Residual Spraying (IRS) for Malaria Control and Child Development in the South African Venda Health Examination of Mothers Babies and their Environment (VHEMBE) birth cohort study located in the Vhembe district of Limpopo, South Africa. According to the World Malaria Report in 2018, IRS is used in 84 countries around the world, exposing more than 100 million people, primarily those living in Africa25. Associations between maternal exposure to DDT and hypertensive disorders of pregnancy26, larger birth size27, and higher body composition measures, and marginally altered motor development were found among VHEMBE girls at age 1 and/or 2 years28. Prenatal exposure to pyrethroids was also associated with lower body composition measures among boys28 and altered motor development among girls aged 1 to 3.5 years30. Given these results and the widespread exposure to these insecticides in African populations, the VHEMBE study has also provided education and outreach to many of the participants to reduce exposure.Dr. Chevrier provided recommendations on starting points for studies interested in assessing exposure to pyrethroids and DDT/DDE (dichlorodiphenyldichloroethylene) and finally, provided an example of his and his colleague’s work in the VHEMBE cohort. He reported that IRS was associated with elevated serum DDT/DDE and urinary pyrethroid metabolite concentrations in peripartum samples collected from 751 VHEMBE women32 to measure 17 trace elements in whole blood samples using Inductively Coupled Plasma Mass Spectrometry as the gold standard method for trace element measurements. No severe deficiencies or toxic levels of trace elements were found. However, the preliminary results suggest a significant association between numerous altered trace element concentrations  with cerebral malaria and severe malarial anemia (unpublished study).Dr. Chandy John from Indiana University School of Medicine described the possible association of trace elements with risk of severe malaria and neurodevelopmental impairment in Kenyan children. Past research has suggested that trace element deficiencies have been associated with increased infection and may also affect cognition. Dr. John discussed the use of various biospecimens  and testing methods for exploring exposures in humans. Whole blood is recommended for providing best blood level measures and hair is useful for evaluation of long-term exposures. Dr. John measured trace metal levels in children during episodes of severe malaria , comparing them to levels for children without malaria to assess the relationship of trace metal levels to risk of severe malaria and cognitive impairment. Dr. John also mentioned the potential ethical, legal, and social issues involved in toxic levels or severe deficiencies of trace elements because of the obligation to report such findings to study participants and because of the political implications of tracing the sources of toxic exposures. The project utilized the NIEHS Children’s Health Exposure Analysis Resource (CHEAR)Participants gathered in smaller groups in the afternoon to discuss common and emerging environmental exposures of interest to H3Africa researchers. Breakout group discussions were focused on exposures of interest including: electronic waste, ambient and indoor air pollution (including tobacco smoke), metals and mycotoxins, pesticides and nutrition/toxicodietary exposures, and biomarkers of chemical exposures and infectious diseases. Each group was asked to comment on the important health outcomes associated with the exposure category, what could be done now to measure exposures of interest in existing studies, example research they may be involved in, training needs to build environmental health research capacity, critical issues for biorepositories storing/managing samples for environmental analysis, and ethical, legal, and social implications. General themes of interest across the breakout group discussions were: identifying what exposures should be measured when studying specific health outcomes, clinical training to recognize symptoms related to hazardous environmental exposures, access to existing data/records/biological samples to assess exposures, use of questionnaires to determine suitability of existing samples for biomarkers of environmental exposures, and biobanking of samples. Key points and discussion from select breakout sessions are provided below.Ambient air pollution was agreed to be a significant hazard in urban areas in Africa, whereas indoor pollution, including indoor cooking, constitutes a problematic exposure in rural areas and slums in large cities. Different cultures and practices across Africa can make comparisons complex and likely require a multidisciplinary approach. Measurements of exposures need to be affordable, robust, validated across different settings, and coordinated through a harmonized approach for data generation and storage. Some African countries monitor and document air pollution, albeit to different levels of complexity and geographic coverage, whereas others have no resources to do so. Despite rare pockets of expertise and activity, there was generally a sense that there was a lack of political will in most African countries to divert resources to monitoring air pollution. Despite the challenges, the group members recognized the importance of air pollution to health and the need to study its effects across the lifespan to further understand the cumulative effects of different pollutants. There was a specific call to action for the use of effective and affordable monitors at a macro (ambient air) and local (indoor cooking exposure and cooking over open fires) level. Such monitors could then be deployed widely for data collection. There are major gaps in infectious disease and environmental exposure research, which represent major opportunities for this field. The impact of chemical exposures on the immune system and susceptibility to infection or progression in infectious diseases has been minimally explored in primary research settings. Exposures considered relevant to infectious diseases included: air pollution , mining, naturally occurring food toxicants and contaminants, pesticides, insecticides, heavy metals, and high voltage power lines. There was also a general interest in the genetics of susceptibility to environmental exposures. Issues of temporality may impact our understanding of how environmental exposures impact infectious diseases. For example, exposures may impair the immune system and make the body more susceptible to infections. Infections may also lead to immunocompromised states and greater susceptibility to the harmful effects of environmental exposures. Disentangling the cause and effect of infection, immunity, environmental exposures, and disease susceptibility was noted as an important consideration for future research, particularly in the context of a well characterized genome.Panelists included Dr. Mark Nicol, from University of Cape Town, Dr. Michèle Ramsay from the University of the Witwatersrand, Dr. Kiros Berhane from University of Southern California, Dr. Brenda Eskenazi, University of California Berkeley, and Dr. Adrie Steyn from the Africa Health Research Institute and University of Alabama Birmingham.Some additional general considerations of study design, chemical properties of exposures , sample types available in study populations, timing of sample collection, variability in exposure levels across individuals, and the complexity of multiple exposures were mentioned in the panel discussion. There was a lengthy dialogue about whether an agnostic approach vs. hypothesis-driven approach was more useful for beginning to explore the impact of different environmental exposures on health outcomes in Africa. Some panelists and the audience felt that targeted hypothesis-directed research would be most effective. This would require further exploration of what might be feasible within existing H3Africa studies. Others felt that an exploratory hypothesis-free approach would be more useful, given that little is known about the range and diversity of exposures present in many African populations. Dr. Nicol advocated for a cross-H3Africa Consortium study of biomarkers of exposure by exploring the possibility of using existing archived specimens to generate an initial broad assessment of relevant exposures using key biomarkers. This might further inform research priorities and assist in developing hypotheses. One challenge with this approach is the selection of biomarkers and the accuracy they would offer as proxies for specific exposures, especially given that the protocols for sample collection varied across studies.PhenX) toolkit and other existing questionnaires were discussed. Dr. Eskenazi mentioned a short questionnaire developed by the International Fetal and Newborn Growth Consortium, which could be used as an example and potentially tailored to African populations. This questionnaire was shared with H3Africa environmental health working group members after the workshop and has been previously described33. There was additional discussion on leveraging prospective H3Africa studies and identifying opportunities for collection of biospecimens. Given that some H3Africa studies were planning for sample collection, there is potential to harmonize the collection, storage, and sampling to assess potential environmental exposures across studies. Investigators could potentially collaborate with other NIEHS-funded investigators and expand their work in existing study populations by collecting environmental data, analyzing stored biospecimens, planning the collection of new biospecimens, or integrating biomonitoring data (e.g. from air monitors or satellites) into their studies. A variety of potential collaborative opportunities or joint publications relating to common environmental exposures, life stages, and health outcomes across different H3Africa study populations might be possible. Some discussion focused on developing and distributing standardized environmental exposure questionnaires. Phenotypes and Exposures , was mentioned as a mechanism to measure more environmental exposures in existing H3Africa or related study populations. Current H3Africa investigators could use CHEAR/HHEAR to explore more environmental exposures in their populations and more broadly study gene-environment (G x E) of complex disease in African populations.The ability to leverage existing expertise to explore the measurement of environmental exposures in different samples was also a key focus of the panel discussion. The NIEHS CHEARPlesiomonas shigelloides in surface waters in Southwest Nigeria, traffic-related air pollution exposure and health outcomes in street vendors in Cape Coast, Ghana, PM2.5 concentrations in Kampala, Uganda, household air pollution and stroke in Ghana and Nigeria, inhaled air pollution and the microbiota of children in the Gambia, pesticide residues in fruits and vegetables in Kampala, Uganda, and characterization of PM2.5 in Addis Ababa. Abstracts for all posters are included in theworkshop meeting book posted on the workshop website.Fifteen poster presentations by trainees covered environmentally focused research efforts that emphasized some of the unique challenges for this field in Africa. Topics highlighted in the posters included: indoor and outdoor air pollution, coal mining exposures, respiratory microbiota, and pesticide exposures. Research presented by these trainees covered topics such as multidrug-resistantTo address the environmental research needs of the H3Africa Consortium, a new H3Africa working group was initiated in 2018, referred to as the H3Africa Environmental Health Working Group. In the coming years, this working group hopes to continue to build on the momentum from the workshop to explore ideas of individual and collaborative projects facilitating the incorporation of environmental risk factors into H3Africa studies. These may include identification of potential collaborative opportunities or joint publications relating to common environmental exposures across different H3Africa study populations. This group will investigate ways to strengthen capacity to measure environmental exposures and expand research in environmental epidemiology, including research on the epigenome and microbiome, and related G x E mechanisms. The group will also discuss ways investigators can expand their work in existing study populations by collecting environmental data through questionnaires, analyzing stored biospecimens for biomarkers of exposures, planning the collection of new biospecimens, or integrating data from air and personal monitors as well as satellite-based environmental data. Attention to the current issues of environmental health research such as mixtures, where multiple environmental/chemical exposures are measured in a sample/individual is also important. Education on the most appropriate statistical methodology for analyzing mixtures data, rather than traditional epidemiology models, has been discussed and ongoing training through webinars, other virtual methods, and in-person meetings is anticipated.34. Leadership by African researchers on studies evaluating multiple environmental exposures, gene-environment interactions, and comparative biology is important and timely. The H3Africa Consortium, with accomplishments in genomic research infrastructure, trained staff, research productivity, and extensive clinical and demographic data across African study populations, represents an ideal platform for advancing African-led environmental health science across the continent. Considering that the environment is a modifiable risk factor, this research has viable application to important intervention and prevention efforts.With developments in technologies to measure environmental exposures, there is opportunity for global progress in environmental health research. In Africa, important environmental research has enabled interventions to reduce harmful exposures . However, much more could be addressed. One of the most pressing concerns identified through this workshop was the underlying need for further characterization of key environmental exposures across varying geographies and populations in Africa. Against the backdrop of challenges of malnutrition, infectious diseases, and limited environmental regulations, the environmental exposure burden of Africans appears to be high, and likely contributes substantially to disease. Importantly, the prevalence of cardiovascular disease, obesity, and diabetes is increasing in African populations, particularly in some geographic regions such as southern Africa, impacting both children and adultsThe views expressed in this article are those of the authors and are not meant to be representative of the affiliated institutions. Publication in AAS Open Research does not imply endorsement by the AAS.Data relating to the survey completed by nine projects prior to the workshop is available in et al. The article discusses the outcome of a workshop on environmental health research in Africa that was organised by the NIEHS in conjunction with the H3Africa Consortium and African Society of Human Genetics. The authors highlight progress made by the H3Africa Consortium and provide justification for more education, training, and research on environmental health to be incorporated within the H3Africa network. Moreover, presentations during the workshop are summarized, the need to leverage on H3Africa network and integrate genomics and environmental health research is discussed. It was thoughtful that during the workshop, H3Africa Environmental Working Group was initiated to explore ways of incorporating environmental risk factors into studies conducted by the H3Africa going forward. Overall, this is an engaging manuscript that highlights the appreciable progress made by the H3Africa Consortium and emphasizes the need to integrate environmental health and genomics research in Africa within the H3Africa studies.This is a compelling letter by JoubertI confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. We thank the reviewer for these positive comments. Approval status – ‘Approved’: One minor change is required.Review:The rationale for this Open Letter was clearly motivated in sufficient detail. The factual statements are correct and adequately supported by citations. The paper also discusses differing views and opinions, where applicable.The Letter is well written in accessible language. The detailed recommendations and next steps provide valuable direction for others to follow.The inclusion of Student Posters in the Letter is highly recommended.This paper also provides a key summary of most published information on environmental data and interests in H3Africa projects. It will be a valuable reference for future use for researchers from Africa.Please check:Page 8 – The header uses “Pesticides” in terms of IRS and it should be “Insecticides”.I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Thank you for the careful review of this manuscript. We agree with the reviewer comments. We will clarify the term pesticides to insecticides when referring specifically to indoor residual spraying (IRS).


Aspergillusspecies widely distributed throughout the environment. These toxins have adverseeffects on humans and livestock at a few micrograms per kilogram (μg/kg)concentrations. Strict regulations on the concentrations of aflatoxins allowedin food and feed exist in many nations in the developing world. Loopholes inimplementing regulations result in the consumption of dangerous concentrationsof aflatoxins. In Kenya, where ‘farm-to-mouth’ crops becomeseverely contaminated, solutions to the aflatoxins problem are needed. Acrossthe decades, aflatoxins have repeatedly caused loss of human and animal life. Aprerequisite to developing viable solutions for managing aflatoxins isunderstanding the geographical distribution and severity of food and feedcontamination, and the impact on lives. This review discusses the scope of theaflatoxins problem and management efforts by various players in Kenya. Economicdrivers likely to influence the choice of aflatoxins management options includehistorical adverse health effects on humans and animals, cost of interventionfor mitigation of aflatoxins, knowledge about aflatoxins and their impact,incentives for aflatoxins safe food and intended scope of use of interventions.It also highlights knowledge gaps that can direct future management efforts.These include: sparse documented information on human exposure; few robust toolsto accurately measure economic impact in widely unstructured value chains; lackof long-term impact studies on benefits of aflatoxins mitigation; inadequatesampling mechanisms in smallholder farms and grain holding stores/containers;overlooking social learning networks in technology uptake and lack of in-depthstudies on an array of aflatoxins control measures followed in households. Thereview proposes improved linkages between agriculture, nutrition and healthsectors to address aflatoxins contamination better. Sustained public awarenessat all levels, capacity building and aflatoxins related policies are necessaryto support management initiatives.Aflatoxins are highly toxic metabolites of several  Aspergillus species.The aflatoxin producing species within section Flavi mostfrequently associated with crop commodities in Africa is the L-strain morphotype ofAspergillus flavus, with lesser occurrences ofAspergillus parasiticus, Aspergillus tamarii,and isolates of S-morphology  show varying contamination levels across the country, withhigh levels reported from eastern Kenya , 2012) and undetectable levels in some other areas. Such contamination has been attributed to growing maize inecologically predisposed regions of Kenya . Even though direct link between exposure and malnutrition was notinvestigated in the study, both counties had stunted and severely stuntedchildren above the national averages of 26% and 11%, respectively  and hasrepresentatives from the agriculture and livestock ministry, Kenya Agriculturaland Livestock Research Organization (KALRO), Ministry of Health, Kenya Bureau ofStandards (KEBS), Kenya Plant Health Inspectorate Services (KEPHIS) and publicuniversities. The task force has since generated reports documenting causativefactors for the 2004-2005 aflatoxicosis outbreak and attributed the outbreak todelayed harvesting, poor storage practices that led to excessive moisture in thegrain and low awareness about aflatoxins. The functions of the task force are,however, currently being replicated by its member institutions, as the awarenessabout the dangers of aflatoxins continues to amplify .The National Food Safety Coordinating Committee (NFSCC) was constituted inFebruary 2006 with broad consultations among stakeholders. The Secretariat isthe Ministry of Health, while the chairmanship lies with the State Department ofAgriculture – Ministry of Agriculture and Irrigation. Its membership isdrawn from ministries/state departments/Semi-Autonomous Government Agencies(SAGA) of health, agriculture, livestock, fisheries and trade; academia; and theCouncil of Governors of the government of Kenya. The Food and AgricultureOrganization of the United Nations (FAO), World Health Organization (WHO), WorldFood Program (WFP), Kenya Association of Manufacturers (KAM) and Cereal MillersAssociation (CMA) are also co-opted members. Its mission is to protectconsumers’ health by ensuring that food produced, distributed, marketed,and consumed meets required standards of food safety. Among its roles are tocoordinate formulation of food safety policies and supportive legal framework,harmonise and coordinate the implementation of food control activities includingfood and feed analysis, inspection, enforce and coordinate food safetyinformation, education and communication (IEC) and monitor and evaluate foodsafety programs.The committee is involved in annual testing for contamination by aflatoxins inmaize, during and after harvest. The exercise is led by the State Department ofAgriculture/NCPB/NFSCC Secretariat. Contaminated maize is subsequentlywithdrawn. Together with FAO, the NFSCC undertook a needs assessment to: (1)identify stakeholders in the maize value chain and their role and responsibilityin the prevention, management and control of aflatoxins contamination; (2)identify and assess the gaps and needs of various stakeholders in their role andresponsibility in prevention, management and control of aflatoxin contamination;and (3) identify and recommend opportunities for aflatoxin prevention andcontrol among various stakeholders. Many recommendations from the needsassessment are currently being implemented and include awareness raising,education for agricultural officers and public health officers  as well as developing capacity for low-cost testing foraflatoxins.In their individual capacity, member institutions of the NFSCC have their ownaflatoxins mitigation initiatives. For example, the government has initiated theWarehouse Receipting System, in collaboration with the NCPB, and committed todrying and storage of farmers’ grain at a fee. In addition, it hasinitiated efforts of purchasing mobile driers for installing at various pointsin the country. Education campaigns are an on-going process in the ministry,with extension officers carrying out education programs just before the maizeseason’s harvest. The ministry of health is tasked to coordinateaflatoxins analyses of samples of maize collected from various parts of thecountry, particularly from highly prone regions . In 2018, the Partnership for Aflatoxin Controlin Kenya (PACK) was conceived during the implementation of a TechnicalCooperation Program (TCP) between the Government of Kenya through the NFSCCmeeting (NFSCC – 2017) and FAO (FAO/NFSCC – TCP/KEN/3402) onprevention and management of aflatoxins along the maize value chain. PACK ismeant to serve as a knowledge and information management platform accessible toall stakeholders. As of this writing, the platform is yet to be formalised, butincountry stakeholder consultations are currently underway .1 in 2007 . The structuring of the relationshipbetween the Kenya government’s agriculture and public health departmentsand FAO presents notable lessons for future initiatives. These lessons includeallocation of resources within on-going government programs to ensure continuityof programs after project completion ; and alignment of its in-country activitieswith the Kenya government’s agricultural agenda, making implementationimpactful.Following the acute aflatoxicosis incidence in 2004 that resulted in numerousdeaths, FAO supported the Ministries of Agriculture and Health officers toidentify causative factors for the outbreak as well as introduce measures toarrest future occurrences. As part of the response, extensive awareness raisingabout aflatoxins was done mainly through public and private sector stakeholdersconsultations both at the national and county levels. The county officers whoparticipated in awareness raising were encouraged to disseminate the sameinformation through et al., The duo conducted epidemiologic investigations to assess exposure levels andresulting health effects, as well as identify modifiable risk and protectivefactors for consuming aflatoxins contaminated food. The US Centres for DiseaseControl and Prevention (CDC) evaluated the performance of rapid screening tests. Assessing the performance of a rapid screeningtool to detect aflatoxins in maize in Eastern Kenya) in rural village settingsand the feasibility and cost-effectiveness of sustaining local food screeningprograms in rural, vulnerable populations. In an intervention study, it wasdemonstrated that inclusion of calcium silicate 100 (ACCS100), a calciummontmorillonite clay in the human diet reduced the bioavailability ofaflatoxins. Although ACCS100 was effective, acceptable, and palatable, theauthors suggested further evaluation of ACCS100 among people in aflatoxins-proneareas and to determine if ACCS100 remains effective at the levels of aflatoxinsexposure that induce aflatoxins poisoning .IITA also partnered with the East African Community (EAC) states and the EACsecretariat to develop technical papers on various topics about aflatoxins. Someof the topics of these papers are pre- and post-harvest management, food andfeed standards, biological control as an aflatoxins management option,aflatoxins and human health, aflatoxins and hepatitis A and B, aflatoxins andthe first 1000 days , and communication. The papersserved as the foundation for the development of policy briefs to enhanceaflatoxins mitigation in the region  centreshave also been instrumental in building local capacity for aflatoxins mitigationthrough short term and long term formal trainings in partnership with local andinternational institutions of learning and within training facilities within theCGIAR centres. For example, IITA has partnered with KALRO to advance capacitybuilding efforts through the East Africa regional mycotoxin research facilitywithin KALRO, while the International Livestock Research Institute (ILRI) hasplayed a similar role through the Biosciences Eastern and Central Africa (BECA)platform, where a mycotoxin training and diagnostics platform exists. ILRI,together with national partners, has also played a significant role to elucidatethe role of aflatoxins in the livestock value chain. The International Maize andWheat Improvement Centre (CIMMYT) has partnered with the national programs toadvance breeding as a long-term measure for pre-harvest aflatoxins mitigation,while the International Food Policy Research Institute (IFPRI) has led effortsto test ready to scale technologies for mitigation of aflatoxins particularlyfor the smallholder farmer and generate human exposure information. TheInternational Crops Research Institute for the Semi-Arid Tropics (ICRISAT) inKenya has focused on establishing the prevalence of aflatoxins in peanuts at thehousehold and market levels, and education on pre-harvest and postharvestmitigation measures for contamination by aflatoxins in peanuts (Grace The Aflatoxin Proficiency Testing and Control in Africa (APTECA) program is beingpiloted in various African countries, including Kenya, where CMA, BECA platform,and several government departments have partnered to advance a quality systemsapproach for managing aflatoxins. The Cereal Growers Association (CGA)continuously partners with private and public-sector players to educate farmerson aflatoxins mitigation and test ready to scale technologies in their mandatemaize growing regions. The Mexican government recently partnered with the publicsector including KALRO and the local universities, as well as private sector toadvance nixtamalization  as a postharvest intervention tomanage aflatoxins in maize grain.etal., The ACDI-VOCA, an international not-for-profit, nong-overnmental organisation hasassisted commercial maize farmers in improving the quality of their grainthrough sound postharvest practices. ACDI-VOCA has also partnered with otherprivate sector players, government, and CGIAR centres to raise awareness aboutaflatoxins among farmers and extension officers through dissemination workshops.The recently concluded AflaSTOP project, a collaboration between ACDI-VOCA,Agribusiness Systems International, Meridian Institute and several public-sectorinstitutions, has generated important information on comparativecost-effectiveness of existing hermetic storage technologies  process set up by the WFP that ensures that the internationalhumanitarian organisation purchases safe and quality grain from farmers afterindependent testing (Meaux The Partnership for Aflatoxin Control in Africa (PACA) has played an importantrole in the mitigation of aflatoxins in Africa. Through the leadership of the AUand supported by a steering committee that has representation across sectors anddisciplines, it has provided a platform for engaging and deliberating solutionsto aflatoxins in the continent to safeguard consumer health and facilitate tradePACA, . Kenya hThe initiatives described above demonstrate the effectiveness of public-privatepartnerships that optimize on each partner’s complementary strengths suchas existing and trusted in-country mechanisms; infrastructure and regulationwithin the public sector to support information and technology dissemination;strong technical backstopping from private sector players; pooling of resourcesfrom partners; mainstreaming proposed initiatives within government structures;and utilizing public and privates sector platforms for informationdissemination.et al. , and test and/or develop mitigation measures. Many mycotoxins co-occur,as their causal agents grow on similar substrates and thrive in similarenvironmental and climatic conditions. On the contrary, sparse information isavailable on human exposure and associated factors, such as contamination levels,sex, age, dietary habits, occupation and immunity  in the reduction of aflatoxins by targeting moisture reduction has beenexplored , policydevelopment and implementation, emergency responses, research, planning and resourcesupport to encourage sustained efforts.The private sector is critical in complementing public sector efforts and providinghuman capacity and technologies through their open access fora. They contribute toinstitutionalising appropriate aflatoxins management systems to ensure thataflatoxins remain under control in the formal food and feed sectors. Joint effortsin advancing the management of aflatoxins must therefore be encouraged.Non-governmental public institutions such as the CGIAR centres have been useful inaugmenting government efforts particularly in technology development anddissemination, while development partners such as United States Agency forInternational Development (government), Bill and Melinda Gates Foundation (private),United Nations Food and Agriculture Organization , the EuropeanUnion , African Union , continue to supplementstate resources to support various interventions. Regional bodies such as COMESA,EAC, and the PACA platform serve a multifaceted role that includes influencingmember states to actively participate in the development and implementation ofaflatoxin interventions; developing aflatoxin related policy and capacity building.Such support notwithstanding, the State must take a lead in setting priorities inmitigation of aflatoxins to ensure sustainability. Efforts must, therefore, beentrenched in the government’s agricultural strategic agenda.et al.,To effectively implement management of aflatoxins, capacity development in the formof human resource base and infrastructure is necessary. The human capacity toaddress various facets of aflatoxins mitigation is still low. Up-to-date researchfacilities for mycotoxin research, for food commodities and human and animalexposure, is required particularly in public institutions. The relevance of sociallearning and networks in promoting aflatoxins mitigation efforts amongst smallholderfarmers need to be considered Ngotho, . Gender Diagnostic tools and testing equipment must be properly targeted. Their applicationneeds to ruminate on cost, availability, rapidity in decision-making process on thetesting outcome, the scale of use, whether the grain is for home or marketconsumption, as well as the capacity of the end user to competently andappropriately use the testing methods. Alongside, sustained public awareness isnecessary to develop a population that is conscious of the benefits of consumingsafe food and consequently demand for it.Finally, government and private sector can play a crucial role in strengtheningpolicies that impact on food safety, as well as support risk assessment initiativesto ensure that well thought out standards for mycotoxins are in place. Scarceresources available to advance management efforts must be utilised well by propertargeting and ensuring that duplication of efforts is minimised. Unlike in severalother countries where trade primarily drives the impacts of aflatoxins and attemptsto get solutions, Kenya has suffered immensely from health impacts to the extentthat the government declared it a national disaster. The incentive to find lastingsolutions to the problem in the country is, therefore, health and trade-based.


Serious infections account for 25% of global newborn deaths annually, most in low-resource settings where hospital-based treatment is not accessible or feasible. In Bangladesh, one-third of neonatal deaths are attributable to serious infection; in 2014, the government adopted new policy for outpatient management of danger signs indicating possible serious bacterial infections (PSBI) when referral was not possible. We conducted implementation research to understand what it takes for a district health team to implement quality outpatient PSBI management per national guidelines.PSBI management was introduced as part of the Comprehensive Newborn Care Package in 2015. The study piloted this package through government health systems with limited partner support to inform scale-up efforts. Data collection included facility register reviews for cases seen at primary level facilities; facility readiness and provider knowledge and skills assessments; household surveys capturing caregiver knowledge of newborn danger signs and care-seeking for newborn illness; and follow-up case tracking, capturing treatment adherence and outcomes. Analysis consisted of descriptive statistics.Over the 15-month implementation period, 1432 young infants received care, of which 649 (45%) were classified as PSBI. Estimated coverage of care-seeking increased from 22% to 42% during the implementation period. Although facility readiness and providers’ skills increased, providers’ adherence to guidelines was not optimal. Among locally managed PSBI cases, 75% completed the oral antibiotic course and 15% received the fourth day follow-up. Care-seeking remained high among private providers (95%), predominantly village health doctors (over 80%).Facility readiness, including health care provider knowledge and skills were strengthened; future efforts should focus on improving provider adherence to guidelines. Social and behavior change strategies targeting families and communities should explore shifting care-seeking from private, possibly less-qualified providers. Strategies to improve private sector management of PSBI cases and improved linkages between private and public sector providers could be explored. Possible serious bacterial Infections (PSBI) or syndromic sepsis is a global public health concern for newborns and young infants 0–59 days), with an estimated 30 million cases per year , 2. Seve9 days, wUp until 2015, the World Health Organization (WHO) recommended inpatient hospital care for all young infants with PSBI and treatment with multi-drug multi-dose injectable antibiotics (penicillin or ampicillin and gentamicin) for 7–10 days . Every cBangladesh is one of 25 Countdown countries that achieved the Millennium Development Goal 4 target , 21. DesIn 2013, the GoB, through its declaration of “A Promise Renewed: Child Survival Call to Action,” committed to the adoption and national scale-up of five new evidence-based newborn health interventions: 1) management of sick young infants with PSBI in primary level care facilities; 2) chlorhexidine application for prevention of cord infection ; 3) antenatal corticosteroids for prevention of complications from preterm labor; 4) kangaroo mother care for small babies; and 5) specialized newborn care units at the upazila (sub-district) and district level , 28. In PSBI in young infants has three sub-classifications: 1) critical illness (CI), 2) clinical severe infection (CSI), and 3) isolated fast breathing (IFB) . National treatment algorithms, referral, and follow-up of cases are detailed in Union Health and Family Welfare Centers (UH&FWCs), primary care facilities at the union level, were selected to serve as the delivery point for outpatient PSBI case management and Upazila Health Complexes (UHCs) as the referral facility. UH&FWCs serve populations of 25,000–35,000 and have a Sub-Assistant Community Medical Officer (SACMO), who has 3 years of clinical training and provides general curative care; most SACMOs have received training in Integrated Management of Childhood Illness.Management of young infants with PSBI at UH&FWCs is carried out by SACMOs, which includes conducting a telephone follow-up of the young infant on day four. Lay field supervisors, called Family Planning Inspectors (FPI), are tasked with conducting follow-up home visits on day eight for PSBI cases managed at the UH&FWC.The Ministry of Health and Family Welfare’s (MOHFW) Directorate General of Health Services (DGHS) and Directorate General of Family Planning (DGFP) selected Kushtia District as a demonstration and learning site to implement the CNCP (hereinafter referred to as a district learning lab), since the district was not receiving any external donor support for maternal and newborn health at the time and the need for newborn care services was high. The purpose of the district learning lab was to demonstrate, using limited external resources and technical support, how the CNCP, and specifically the new interventions, could be effectively and sustainably scaled-up at district level within the existing public health structure using local resources and budgets. While the aim of this work was to document and share learning to inform the national scale-up of the full CNCP, the focus of this paper is on the learning from the implementation research of management of young infants with PSBI.The CNCP was formally launched in Kushtia District in early 2015, covering the district’s six upazilas . SNL provided technical support to DGHS and DGFP for implementation start-up, with activities focused on: advocacy and policy support for improving national and district-level readiness for PSBI case management; building the capacity of the health care providers in PSBI case management; improving health facility readiness; monitoring and supervision of implementation to inform program adaptation; and promoting the use of newborn care services at UH&FWCs through community awareness and engagement. Implementation of PSBI case management in UH&FWCs began in October 2015.SNL provided advocacy and technical support to the MOHFW to facilitate necessary policy changes for implementation of the new guidelines for PSBI case management at UH&FWCs. This support included technical assistance in the development and dissemination of the national guideline on PSBI case management. SNL helped advocate for a policy change to allow SACMOs working under DGFP to administer injectable gentamicin. In addition, the DGFP drug list was updated to include injectable gentamicin, which previously was only available through the DGHS. PSBI commodity distribution guidelines were also developed for health care managers and providers.Capacity building focused on knowledge and skills development and retention. Formal training on the national guidelines for PSBI case management was provided as part of the CNCP training for different health care provider cadres. The SACMOs received a five-day CNCP training that included a half-day on identification and management of PSBI. In addition, SACMOs also received a one-day orientation on the sick newborn and young infant service register, reporting forms, and two jobs aids . Mini skills labs were set up with SNL support at UHCs to facilitate on-site practice of provider skills in PSBI recognition and management, with mock practice sessions conducted during monitoring visits and at monthly SACMO meetings. On-the-job mentoring was provided to SACMOs by upazila level managers, who served as mentors and provided advice and feedback during routine visits to facilities. FPIs received a four-day training covering counseling and awareness on newborn danger signs, community awareness and engagement responsibilities, and provision of follow-up care for young infants with PSBI who receive outpatient treatment.SNL provided support to the DGHS and DGFP to strengthen the readiness of the UH&FWCs, specifically to ensure availability of newborn medicines, equipment, supplies, and logistics. Given CNCP was introducing new interventions, drugs and commodities required for management of young infants with PSBI were not initially on the MOHFW procurement list. As an interim measure, SNL procured and distributed commodities  through existing government distribution structures to all the UH&FWCs in Kushtia. SNL also provided the district hospital, UHCs, and UH&FWCs with the necessary initial equipment  timers) for management of young infants with PSBI. An orientation and follow-up technical support was provided to district and upazila level storekeepers and pharmacists on newborn-related logistics management, including support to strengthen the reporting system on monthly consumption. The MOHFW, through the DGHS and DGFP, began procuring and distributing commodities for PSBI in June 2017.Several monitoring and supervision tools were developed with technical support from SNL. A sick newborn and young infant service register and reporting forms were developed to record and monitor PSBI case management and commodity stocks at the facility level. A PSBI surveillance reporting form was developed for the FPIs to use to track follow-up home visits on day eight. Additionally, a referral form was introduced to strengthen the linkage between the UH&FWCs and referral facilities (UHC) for PSBI case management, and a UH&FWC monitoring checklist was developed to guide supervisory visits . District and upazila level managers carried out routine facility visits to UH&FWCs, where they monitored PSBI case management activity, checked stock and equipment status, reviewed registers and reporting forms, and assessed provider knowledge retention. SNL staff accompanied upazila managers on supervisory visits to build capacity; and, after approximately a year of implementation, gradually shifted away from providing this support. These supervisory visits were guided by the UH&FWC monitoring checklist to ensure all components were addressed during visits. Observations from these supervisory visits were discussed in routine monthly upazila level staff meetings. Additionally, quarterly one-day review meetings were organized for SACMOs to review registers, analyze data on PSBI cases, and assess and address gaps in provider adherence to the national guidelines. Quarterly meetings also served as an opportunity to identify and address data reporting issues and errors.As part of CNCP, a social and behavior change (SBC) campaign was developed and implemented in Kushtia. For PSBI, the campaign focused on increasing awareness of newborn danger signs and promotion of early care-seeking at UH&FWCs. SBC approaches included:Education and awareness raising through routine contacts with government community health workers  and during visits to health facilities. As part of the CNCP training, health care providers at community, union, and upazila levels, were oriented on and provided with different SBC materials for counseling clients during antenatal, delivery, and postnatal care contacts .Community education to improve knowledge of newborn danger signs and early care-seeking at UH&FWCs. Community groups and community support groups received an orientation on the CNCP and were provided with educational materials (a flip sheet and a booklet) to use during group sessions.TV spots aired through local cable networks on essential newborn care and newborn danger signs, and posters on newborn danger signs were placed in the waiting areas of health facilities .A summary of the different implementation activities, inputs, and the timeline for the district learning lab in Kushtia can be found in the This study was implemented in Kushtia District, approximately 200 kilometers west of Dhaka, Bangladesh’s capital. At the time of the study, the neonatal mortality rate in Kushtia was 36 deaths per 1,000 live births, slightly higher than the national average of 32 deaths per 1,000 live births  . A secondary objective of the study was to assess changes in caregiver knowledge of newborn danger signs and in care-seeking for newborn illness.We employed the following quantitative methods of data collection: repeated rounds of health facility readiness assessment surveys; repeated rounds of health care provider knowledge and skill assessment surveys; continuous data extraction from the UH&FWC sick newborn and young infant service registers; follow-up interviews with caregivers of sick young infants who received care at UH&FWCs; and repeated rounds of household surveys in the selected unions. The study was implemented over a 15-month period (divided into 5 quarters), between December 2015 and February 2017; in addition, select pre and post-implementation assessments were conducted. The study population included young infants with signs of PSBI receiving care from the selected UH&FWCs and their primary caregivers, health care providers in the selected UH&FWCs responsible for identifying and treating PSBI, and women with a recent history of childbirth in the selected unions.For the health facility assessment surveys, all UH&FWCs in the selected unions were approached for assessment. Of the 36 UH&FWCs in the 30 unions, 29, 30, 34, 34, and 34 were assessed across the five rounds of surveys, respectively; not all 36 UH&FWCs could be assessed in every round due to non-availability of SACMOs.For the knowledge and skill assessments, three rounds of surveys were conducted of 30, 31, and 34 SACMOs, respectively. The rounds of knowledge and skill assessments were independent of the rounds of health facility assessments.Data extraction was conducted weekly from the newborn and young infant service registers from the selected UH&FWCs throughout the study implementation period (December 2015–February 2017). A total of 1440 records for young infants receiving care with signs of PSBI and other illness were extracted over the 15-month period, of which 1432 were less than 60 days of age on the day of their health facility visit.Follow-up visits and household interviews with primary caregivers were attempted between 7–14 days after the initial UH&FWC visit, for all sick young infants identified from the UH&FWC registers. A total of 1243 follow-up visits were completed, 1087 within the target 7–14 day window.For the household survey, a stratified sampling technique was used to ensure equal representation of all selected unions from the three upazilas. Villages were considered as the primary sampling unit. Probability proportional to size sampling was used to select 17 villages from each union. From the selected villages, all women with a recent history of childbirth (in the three months preceding the survey) were identified. A total of 4436 women were interviewed through four rounds of surveys during the study period.The health facility assessments were conducted by trained study physicians using a structured assessment tool that had specific sections on service availability and readiness for PSBI case management. The knowledge and skill assessment surveys were conducted on SACMOs by trained study physicians with a structured interview questionnaire and checklist. The tool had specific questions on knowledge regarding the PSBI classification and management guidelines, and a skills assessment section that presented different hypothetical case scenarios.The data extraction was conducted by trained data collectors using a structured extraction tool. All variables available in the sick newborn and young infant service registers , were extracted. The follow-up visits were conducted in the households of sick young infants by trained study nurses using a structured questionnaire. The study nurses conducted a clinical assessment to assess the condition of the young infants on the day of the visit and interviewed primary caregivers regarding care-seeking practices and adherence to treatment advice.The household survey was conducted by trained data collectors with an interviewer-administered structured questionnaire. The questionnaire included questions on background characteristics and sociodemographic information, caregiver knowledge of newborn danger signs, and care-seeking practices.Descriptive statistics were used to report readiness of UH&FWCs for PSBI case management, knowledge and skills of SACMOs, utilization of UH&FWCs by young infants, adherence to treatment protocol by SACMOs and treatment advice by caregivers, treatment failure rates, knowledge of caregivers regarding newborn danger signs, and care-seeking by caregivers for sick young infants. Changes in these indicators are presented by quarter.Health facility readiness was scored based on the availability of 10 essential items for managing PSBI according to the national guidelines. These items included oral amoxicillin, injectable gentamicin, insulin syringes, baby weighing machine, thermometer, ARI timer, sick newborn and young infant service registers, prescription with referral slip, and two job aids . The items were selected based on consultation with clinical experts and national health managers. Facility readiness was categorized as poor (0–4 items), moderate (5–7 items), and good (8–10 items) based on their availability. Information on functionality was collected for baby weighing machines, thermometers, and ARI timers in three of the five assessment rounds.Coverage at UH&FWCs of young infants with PSBI presenting for care was estimated, assuming a population incidence of 9.5 PSBI cases per 100 young infants , then diAdherence to treatment was calculated based on caregiver recall of receiving injectable and oral drugs at UH&FWCs and giving oral antibiotics at home, collected through the follow-up interviews with caregivers. Treatment failure was defined as the presence of any danger sign, including signs of CI, CSI, and IFB, as assessed by study nurses during the follow-up household visits conducted on days 7–14.Knowledge of caregivers regarding newborn danger signs was calculated based on 14 items (Annex 1). Any woman who could mention (unprompted) four or more danger signs was considered to have good knowledge.Data were analyzed using Stata 14.0 .The data collectors received extensive training by the study investigators before starting data collection. Biweekly refresher trainings were held to discuss data quality issues. Field supervisors conducted regular spot checks to assess the quality of data collection. Additionally, monthly supervisory visits and random spot checks were conducted by study investigators. Finally, all filled-in questionnaires were reviewed by field supervisors and field managers before data entry.Ethical approval for the study was obtained from the Institutional Review Board of icddr,b (Protocol Number: PR 15074) and the Save the Children Ethics Research Committee in the United States. Written informed consent was obtained from all participants before beginning interviews. Privacy, anonymity, and confidentiality of the participants were strictly maintained during data collection and analysis.UH&FWCs readiness for management of young infants with PSBI is presented in Overall, health care providers’ skills in PSBI assessment improved from the beginning of implementation (quarter 1) through the post implementation phase . The larBackground characteristics of women with a recent history of birth in the three months preceding the survey are presented in the Women’s knowledge of newborn danger signs improved gradually over the 15-month implementation period, from 28% in quarter 1 to 42% in quarter 5 . Across This study examined the feasibility of implementing the national guidelines for PSBI case management as part of the CNCP in Kushtia, with a focus on assessing the utilization and quality of PSBI case management in primary level UH&FWCs in the district. The study showed that UH&FWC readiness for PSBI case management gradually improved over the implementation period, with a substantial improvement observed between pre-implementation and the first quarter of implementation. Health system inputs provided to the UH&FWCs were targeted to ensure the essential elements required for PSBI case management were available. Initial equipment and commodity inputs were provided by the program at the beginning of implementation to help ensure health facility readiness and then gradually this role was transitioned to the GoB. The post-implementation results show all facilities with a higher score on the readiness index, indicating that health facility readiness for PSBI case management was sustained through the local health system structures. Similar improvements in the knowledge and skills of SACMOs in PSBI case management were observed across the three rounds of health care provider assessments, despite the low caseload managed by providers . These results suggest that the capacity building and skill retention strategies implemented in Kushtia helped to sustain provider theoretical knowledge and skills around assessment and treatment for PSBI.Quarterly data on sick young infant cases managed at UH&FWCs (from the data extraction records) showed a gradual increase in cases seen over the 15-month implementation period; however, most of the increase was for less severe infections (IFB and LBI) and for cases classified as other. The number of CI cases seen at UH&FWCs remained very low over the implementation period, and CSI cases only showed a small increase in the last two quarters. The household survey data similarly showed a small increase in care-seeking for sick young infants at UH&FWCs (from 1.5% in quarter 1 to 5% in quarter 5). Estimates of PSBI case incidence in young infants 0–59 days from the recent Aetiology of Neonatal Infection in South Asia (ANISA) study show incidence at 9.5% ; using tMultiple factors likely contributed to low utilization of UH&FWCs for care of sick young infants. The CNCP introduced in Kushtia included new interventions not historically offered in the UH&FWCs. While community awareness and demand generation strategies were included in the overall CNCP strategy as a means to improve awareness of newborn danger signs and care-seeking for newborn health services at UH&FWCs, they may have not been sufficient to build awareness and observe substantive changes in care-seeking. Data on the reach and quality of implementation of these strategies were not systematically collected in the study. However, programmatic documentation indicates that implementation of the community awareness activities may have lagged and not been implemented consistently in all sites, suggesting there likely was insufficient time and activities for greater changes in care-seeking to be observed. Data from the household surveys did show a modest increase in caregiver knowledge of newborn danger signs (from 28% in quarter 1 to 42% in quarter 5) and a small increase in care-seeking from UH&FWCs, indicating some improvement over the implementation period . While tHealth care provider adherence to the guidelines for managing PSBI cases, assessed through caregiver report, was not optimal. While the number of CI cases managed at the UH&FWCs was small, only six of the eight were referred and provided the proper pre-referral treatment. Among CSI cases managed by SACMOs at the UH&FWCs, only 69% of caregivers reported having received the first dose of injectable gentamicin and just 56%, the two required doses. For IFB cases, only 64% of caregivers reported receiving amoxicillin from the health care provider for treatment at home. Overall, health care provider adherence to the treatment protocol in Kushtia appears to have been lower than other study sites in sub-Saharan Africa  and South Asia  . ProjectThe caregiver interviews indicate that the majority of PSBI cases that were supposed to be referred per the national guideline were not . The majority of cases that reported having received a referral also reported not accepting the referral, instead choosing to have the infant treated at the UH&FWC. Reasons for the low adherence to the protocol by providers are not clear; given the results are based on the caregiver report, there is the possibility of recall or social desirability bias. The exception was the CI cases, where the majority (six of eight) reporting being referred and accepting referral.Provider adherence to the follow-up protocol in Kushtia was substantially lower than in other study sites, which reported follow-up adherence of 90% or higher ; it is pTreatment failure, measured as the presence of any PSBI signs or symptoms between 7 and 14 days, was minimal in the study. Among CI, CSI, and IFB cases managed locally, treatment failure was observed in 3.9% of cases, all among IFB cases. No deaths were reported in the 15-month implementation period among cases seen in UH&FWCs. Treatment failure in other study sites have ranged from less than 1% to 12% , 41, 42;Overall, the results suggest that while improvements and retention of SACMOs knowledge and skills in PSBI case management were measured, these are not necessarily translating into actual practice and adherence to the national guidelines by providers. This could be in part due to the logistical challenges noted, including caregiver inability to adhere to referral, drug stockouts, issues with functionality of equipment, and challenges in conducting follow-up visits. However, given the overall poor adherence observed, this should be further explored to better characterize the key barriers to improve provider adherence to PSBI guidelines and identify potential solutions. The study findings also showed care-seeking among private and informal providers, particularly from local village doctors, remained high throughout the implementation period. While modest changes were observed in care-seeking at public facilities, the findings suggest that the CNCP SBC strategy and its implementation should be revisited to influence care-seeking behavior. Moreover, future efforts should also explore possible engagement of the private sector to improve sick young infant treatment for PSBI.Completion of the community follow-up interviews with caregivers of sick young infant cases was challenging; only 87% (1243 of 1432 cases) of cases identified at the UH&FWCs were successfully followed-up after the initial visit at the UH&FWC, and only 76% (1087 of 1432 cases) of the cases received a follow-up visit within the desired 7–14 day timeframe. Given provider and caregiver adherence to the national guidelines, and treatment failure were assessed during the follow-up interviews with caregivers, it is possible that cases not followed-up were different from those that were followed-up, potentially biasing the results. Furthermore, provider adherence to PSBI guidelines was determined based on caregiver recall, and was therefore subject to recall error. While data extracted from facility registers could have provided additional insight on protocol adherence and treatment follow-up, problems with completeness and proper completion limited their usability. Given the low caseload of CI and CSI cases, results on health provider and caregiver adherence to the treatment protocol and treatment failure were presented only for the full 15-month implementation period rather than by quarter, limiting the study’s ability to assess possible changes in treatment adherence and treatment failure over time.This paper presents the key findings and lessons from the early implementation experience of managing young infants with PSBI at primary level health facilities in Kushtia District. Findings show some improvements over the implementation period in health facility readiness for PSBI case management and in provider skills to provide PSBI case management, as well as caregiver knowledge of newborn danger signs and relatively good adherence to treatment advice. However, despite the various inputs provided and approaches used to improve and sustain health care provider knowledge and skills for PSBI case management, provider adherence to the national guideline was below optimal. Future efforts to implement the guidelines need to explore factors influencing provider behaviors. Finally, for higher effective coverage of outpatient management of PSBI when referral is not feasible, SBC strategies targeting families and communities need to be fine-tuned to shift care-seeking from private, possibly less-qualified providers. Alternately, strategies to improve private sector management of PSBI cases and improved linkages between private and public sector providers may need to be explored.S1 Appendix(DOCX)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S5 Table(DOCX)Click here for additional data file.S1 Fig(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.S3 Fig(TIF)Click here for additional data file.S4 Fig(TIF)Click here for additional data file.S5 Fig(TIF)Click here for additional data file.S1 Dataset(DTA)Click here for additional data file.S2 Dataset(DTA)Click here for additional data file.S3 Dataset(DTA)Click here for additional data file.S4 Dataset(DTA)Click here for additional data file.S5 Dataset(DTA)Click here for additional data file.


Aging theories suggest that diversity of experiences relates to social integration, cognitive reserve, and more psychological resources, all of which are important for successful aging. However, age-related declines may contribute to a monotonous daily life. Emerging studies suggest that activity diversity and positive emotional diversity are associated with better health; yet, we still know little about how a variety of diverse lifestyle indicators are associated with health in adulthood. This symposium showcases contemporary endeavors towards understanding how multiple diversity indicators of adult lifestyle relate to health. Paper 1 examines activity diversity (breadth and evenness of daily activity participation) and tests its associations with overall and nightly sleep health. Paper 2 investigates the relationship between activity diversity and hippocampus volume. Paper 3 examines whether there are age-related differences in the extent to which positive emodiversity attenuates the association between stress and depressive symptoms. Paper 4 examines stressor diversity and how it is associated with blood pressure across age and SES. Paper 5 introduces a novel concept of happyversity (diversity in life satisfaction across different domains) and tests its association with terminal decline. These papers use different project datasets that include different populations of middle-aged and older adults, such as the Midlife in the United States Study, Intraindividual Study of Affect, Health and Interpersonal Behavior, Study of Health and Interactions in the Natural Environment, and German Socioeconomic Panel Study. At the end of these presentations, Dr. Almeida will discuss their theoretical and methodological contributions, and consider challenges and opportunities for future research.