Enteric Permeability, Systemic Inflammation, and Post-Discharge Growth Among a Cohort of Hospitalized Children in Kenya and Pakistan.

OBJECTIVES: To determine whether gut permeability is associated with post-discharge growth and systemic inflammation among hospitalized children in low- and middle-income countries. METHODS: Children aged 2-23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose-rhamnose ratio (LRR) permeability testing and were compared to age-matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length-for-age (LAZ) and weight-for-age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation [C-reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin-6 (IL-6)], and enterocyte damage [Intestinal Fatty-Acid Binding protein (I-FABP)] differed between the hospitalized and community groups. RESULTS: One hundred thirty-seven hospitalized and 84 community participants were included. The hospitalized group had higher log-LRR [0.43, 95% confidence interval (CI): 0.15-0.71, P = 0.003] than the community children. Adjustment for weight-for-length z score at discharge attenuated this association (0.31, 95% CI: 0.00-0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post-discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα ( P = 0.017), CD14 ( P = 0.078), and IL-6 ( P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα ( P = 0.004) and approached significance with CD14 ( P = 0.078) and IL-6 ( P = 0.062) in community children, but there was no evidence of these associations among hospitalized children. CONCLUSIONS: Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children.

Strengthening the role of community health workers in supporting the recovery of ill, undernourished children post hospital discharge: qualitative insights from key stakeholders in Bangladesh and Kenya.

BACKGROUND: Undernourished children in low- and middle-income countries remain at elevated risk of death following hospital discharge, even when treated during hospitalisation using World Health Organisation recommended guidelines. The role of community health workers (CHWs) in supporting post-discharge recovery to improve outcomes has not been adequately explored. METHODS: This paper draws on qualitative research conducted as part of the Childhood Acute Illnesses and Nutrition (CHAIN) Network in Bangladesh and Kenya. We interviewed family members of 64 acutely ill children admitted across four hospitals (a rural and urban hospital in each country). 27 children had severe wasting or kwashiorkor on admission. Family members were interviewed in their homes soon after discharge, and up to three further times over the following six to fourteen months. These data were supplemented by observations in facilities and homes, key informant interviews with CHWs and policy makers, and a review of relevant guidelines. RESULTS: Guidelines suggest that CHWs could play a role in supporting recovery of undernourished children post-discharge, but the mechanisms to link CHWs into post-discharge support processes are not specified. Few families we interviewed reported any interactions with CHWs post-discharge, especially in Kenya, despite our data suggesting that opportunities for CHWs to assist families post-discharge include providing context sensitive information and education, identification of danger signs, and supporting linkages with community-based services and interventions. Although CHWs are generally present in communities, challenges they face in conducting their roles include unmanageable workloads, few incentives, lack of equipment and supplies and inadequate support from supervisors and some community members. CONCLUSION: A multi-pronged approach before or on discharge is needed to strengthen linkages between CHWs and children vulnerable to poor outcomes, supported by clear guidance. To encourage scale-ability and cost-effectiveness of interventions, the most vulnerable, high-risk children, should be targeted, including undernourished children. Intervention designs must also take into account existing health worker shortages and training levels, including for CHWs, and how any new tasks or personnel are incorporated into hospital and broader health system hierarchies and systems. Any such interventions will need to be evaluated in carefully designed studies, including tracking for unintended consequences.

Identifying opportunities to optimize mass drug administration for soil-transmitted helminths: A visualization and descriptive analysis using process mapping.

BACKGROUND: The control of soil-transmitted helminths (STH) is achieved through mass drug administration (MDA) with deworming medications targeting children and other high-risk groups. Recent evidence suggests that it may be possible to interrupt STH transmission by deworming individuals of all ages via community-wide MDA (cMDA). However, a change in delivery platforms will require altering implementation processes. METHODS: We used process mapping, an operational research methodology, to describe the activities required for effective implementation of school-based and cMDA in 18 heterogenous areas and over three years in Benin, India, and Malawi. Planned activities were identified during workshops prior to initiation of a large cMDA trial (the DeWorm3 trial). The process maps were updated annually post-implementation, including adding or removing activities (e.g., adaptations) and determining whether activities occurred according to plan. Descriptive analyses were performed to quantify differences and similarities at baseline and over three implementation years. Comparative analyses were also conducted between study sites and areas implementing school-based vs. cMDA. Digitized process maps were developed to provide a visualization of MDA processes and inspected to identify implementation bottlenecks and inefficient activity flows. RESULTS: Across three years and all clusters, implementation of cMDA required an average of 13 additional distinct activities and was adapted more often (5.2 adaptations per year) than school-based MDA. An average of 41% of activities across both MDA platforms did not occur according to planned timelines; however, deviations were often purposeful to improve implementation efficiency or effectiveness. Visualized process maps demonstrated that receipt of drugs at the local level may be an implementation bottleneck. Many activities rely on the effective setting of MDA dates and estimating quantity of drugs, suggesting that the timing of these activities is important to meet planned programmatic outcomes. CONCLUSION: Implementation processes were heterogenous across settings, suggesting that MDA is highly context and resource dependent and that there are many viable ways to implement MDA. Process mapping could be deployed to support a transition from a school-based control program to community-wide STH transmission interruption program and potentially to enable integration with other community-based campaigns. TRIAL REGISTRATION: NCT03014167.

Depressive symptoms among mothers with hospitalized children in South Asia and sub-Saharan Africa.

BACKGROUND: Poor maternal mental health during childhood hospitalization is associated with post-discharge child mortality. We aimed to establish if maternal PHQ-9 scores during hospitalization are associated with acute stressors or longer trends in mental health status. METHOD: Mothers of children admitted to nine hospitals in six countries completed a PHQ-9 assessment during hospitalization and 45-days post-discharge. Community participants were recruited from homes near the hospitalized children. The prevalence and correlates of high PHQ-9 scores among hospitalized and community mothers were compared. OUTCOMES: Among 2762 mothers of hospitalized children, 514 (19 %) had PHQ-9 scores ≥10, significantly more than the 116 (10 %, p < 0·001) of 1159 community participants. Recruitment site and food insecurity were PHQ-9 correlates in both groups. Correlates of higher mean PHQ-9 scores among the hospitalized cohort included maternal illness (mean difference [MD]: 1·27, 95%CI: 0·77, 1·77), pregnancy (MD: 0·77, 95%CI: 0·27, 1·28), child HIV-infection (MD: 2·51. 95%CI: 1·55, 3·52), and lower child weight-for-height (MD: 0·21, 95%CI: 0·32, 0·11). Marriage (MD -0·92, 95%CI: -1·36, -0·48) and a positive malaria test (MD: -0·63, 95%CI: -1·15, -0·10) were associated with lower PHQ-9 scores among mothers of hospitalized children. Among mothers with PHQ-9 ≥10 during admission, 410 had repeat assessments 45-days after their child's discharge, and 108 (26 %) continued to meet the high PHQ-9 criterion. INTERPRETATION: Among mothers of hospitalized children, there are subgroups with transient and persistent depressive symptoms. Interventions tailored to address acute stressors may improve post-discharge pediatric and maternal health outcomes. FUNDING: Bill & Melinda Gates Foundation OPP1131320.

Policy stakeholder perspectives on barriers and facilitators to launching a community-wide mass drug administration program for soil-transmitted helminths.

BACKGROUND: Recent evidence suggests that soil-transmitted helminth (STH) transmission interruption may be feasible through community-wide mass drug administration (cMDA) that deworms community members of all ages. A change from school-based deworming to cMDA will require reconfiguring of STH programs in endemic countries. We conducted formative qualitative research in Benin, India, and Malawi to identify barriers and facilitators to successfully launching a cMDA program from the policy-stakeholder perspective. METHODS: We conducted 40 key informant interviews with policy stakeholders identified as critical change agents at national, state/district, and sub-district levels. Participants included World Health Organization country office staff, implementing partners, and national and sub-national government officials. We used the Consolidated Framework for Implementation Research to guide data collection, coding, and analysis. Heat maps were used to organize coded data and differentiate perceived facilitators and barriers to launching cMDA by stakeholder. RESULTS: Key facilitators to launching a cMDA program included availability of high-quality, tailored sensitization materials, and human and material resources that could be leveraged from previous MDA campaigns. Key barriers included the potential to overburden existing health workers, uncertainty of external funding to sustain a cMDA program, and concerns about weak intragovernmental coordination to implement cMDA. Cross-cutting themes included the need for rigorous trial evidence on STH transmission interruption to gain confidence in cMDA, and implementation evidence to effectively operationalize cMDA. Importantly, if policy stakeholders anticipate a cMDA program cannot be sustained due to cost and human resource barriers in the long term they may be less likely to support the launch of a program in the short term. CONCLUSIONS: Overall, policy stakeholders were optimistic about implementing cMDA primarily because they believe that the tools necessary to successfully implement cMDA are already available. Policy stakeholders in this study were cautiously optimistic about launching cMDA to achieve STH transmission interruption and believe that it is feasible to implement. However, launching cMDA as an alternative policy to school-based deworming will require addressing key resource and evidence barriers. Trial registration This study was registered in the U.S. National Library of Medicine Clinical Trials registry (NCT03014167).

Community Drug Distributor Knowledge, Attitudes, and Motivation Surrounding Mass Drug Administration for Soil-Transmitted Helminths in India.

Background: DeWorm3 is an ongoing multi-country community-based cluster-randomized trial assessing the feasibility of interrupting transmission of soil-transmitted helminths (STH) with community-wide mass drug administration (cMDA). In Tamil Nadu, India, community drug distributors (CDDs) worked with DeWorm3 field staff to counsel community members and deliver door-to-door deworming treatment. As CDDs were likely to influence successful delivery of cMDA, we describe drivers of CDDs' knowledge, attitudes, and motivation toward delivery of cMDA. Methods: In this convergent mixed-methods study, a questionnaire on STH and cMDA was administered to 104 CDDs and 17 focus group discussions (FGDs) were conducted. Key outcomes in the quantitative and qualitative analyses included CDDs' knowledge about STH and cMDA and attitudes toward cMDA for STH. Univariate and multivariable logistic regression analyses were performed to determine the strength of associations between independent and outcome variables. The FGDs were analyzed using a priori thematic coding. Results: CDDs who completed at least secondary school education [adjusted odds ratio (aOR): 2.71, 95% CI: 1.16-6.33] and had prior experience in health programs (aOR: 2.72, 95% CI: 1.15-6.44) were more knowledgeable about STH and cMDA. CDDs belonging to the scheduled castes and scheduled tribes (aOR: 2.37, 95% CI: 1.04-5.39), and to households engaged in a skilled occupation (aOR: 2.77, 95% CI: 1.21-6.34) had a more positive attitude toward cMDA for STH. The FGDs showed that while there were myths and misconceptions about STH, many CDDs believed that the adult population in their communities were infected with STH, and that a door-to-door drug delivery strategy would be optimal to reach adults. Conclusions: Educational and socioeconomic backgrounds and experience in health programs should be considered while designing CDD trainings. Along with cMDA delivery for STH, as CDD do share community myths and misconceptions around STH, they should be proactively addressed during the CDD training to strengthen competency in counseling.

Structural readiness to implement community-wide mass drug administration programs for soil-transmitted helminth elimination: results from a three-country hybrid study.

BACKGROUND: Current soil-transmitted helminth (STH) control programs target pre-school and school-age children with mass drug administration (MDA) of deworming medications, reducing morbidity without interrupting ongoing transmission. However, evidence suggests that STH elimination may be possible if MDA is delivered to all community members. Such a change to the STH standard-of-care would require substantial systems redesign. We measured baseline structural readiness to launch community-wide MDA for STH in Benin, India, and Malawi. METHODS: After field piloting and adaptation, the structural readiness survey included two constructs: Organizational Readiness for Implementing Change and Organizational Capacity for Change. Sub-constructs of organizational readiness include change commitment and change efficacy. Sub-constructs of organizational capacity include flexibility, organizational structure, and demonstrated capacity. Survey items were also separately organized into seven implementation domains. Surveys were administered to policymakers, mid-level managers, and implementers in each country using a five-point Likert scale. Item, sub-construct, construct, and domain-level medians and interquartile ranges were calculated for each stakeholder level within each country. RESULTS: Median organizational readiness for change scores were highest in Malawi (5.0 for all stakeholder groups). In India, scores were 5.0, 4.0, and 5.0 while in Benin, scores were 4.0, 3.0, and 4.0 for policymakers, mid-level managers, and implementers, respectively. Median change commitment was equal to or higher than median change efficacy across all countries and stakeholder groups. Median organizational capacity for change was highest in India, with a median of 4.5 for policymakers and mid-level managers and 5.0 for implementers. In Malawi, the median capacity was 4.0 for policymakers and implementers, and 3.5 for mid-level managers. In Benin, the median capacity was 4.0 for policymakers and 3.0 for mid-level managers and implementers. Median sub-construct scores varied by stakeholder and country. Across countries, items reflective of the implementation domain 'policy environment' were highest while items reflective of the 'human resource' domain were consistently lower. CONCLUSION: Across all countries, stakeholders valued community-wide MDA for STH but had less confidence in their collective ability to effectively implement it. Perceived capacity varied by stakeholder group, highlighting the importance of accounting for multi-level stakeholder perspectives when determining organizational preparedness to launch new public health initiatives. TRIAL REGISTRATION: NCT03014167.

Challenges in Assessing Combined Interventions to Promote Linear Growth.

Despite the recognition of stunting as a public health priority, nutritional and nonnutritional interventions to reduce or prevent linear growth failure have demonstrated minimal impact. Investigators and policymakers face several challenges that limit their ability to assess the potential benefits of combining available interventions into a linear growth promotion package. We use two common but very different interventions, deworming and multiple micronutrient supplements, to illustrate barriers to recommending an optimal linear growth promotion package based on the currently available literature. These challenges suggest that combining individual- and population-based as well as model-based approaches would complement existing research using systematic review, meta-analysis, and factorial randomized trials, and help integrate existing fields of research to inform the development of optimal linear growth promotion packages for children living in resource-limited settings.

Management of diarrhea in HIV-affected infants and children.

Globally, diarrhea is the second leading cause of death in children less than 5 years of age. HIV-infected and HIV-exposed uninfected (HEU) children are at high risk of dying from diarrhea and may be more susceptible to the highest risk enteric pathogens. This increased risk associated with HIV infection and HIV exposure is likely multifactorial. Factors such as immunosuppression, proximity to individuals more likely to be shedding pathogens, and exposure to antimicrobial prophylaxis may alter the risk profile in these children. Current international guidelines do not differentiate management strategies on the basis of whether children are infected or affected by HIV, despite likely differences in etiologies and consequences. Reducing diarrhea mortality in high HIV prevalence settings will require strengthening of HIV testing and treatment programs; improvements in water, sanitation and hygiene interventions targeted at HIV-affected households; and reconsideration of the use of empiric antimicrobial treatment of pathogens known to infect HIV-infected and HEU children disproportionately.

Schistosomiasis elimination strategies and potential role of a vaccine in achieving global health goals.

In March 2013, the National Institute of Allergy and Infectious Diseases and the Bill and Melinda Gates Foundation co-sponsored a meeting entitled "Schistosomiasis Elimination Strategy and Potential Role of a Vaccine in Achieving Global Health Goals" to discuss the potential role of schistosomiasis vaccines and other tools in the context of schistosomiasis control and elimination strategies. It was concluded that although schistosomiasis elimination in some focal areas may be achievable through current mass drug administration programs, global control and elimination will face several significant scientific and operational challenges, and will require an integrated approach with other, additional interventions. These challenges include vector (snail) control; environmental modification; water, sanitation, and hygiene; and other future innovative tools such as vaccines. Defining a clear product development plan that reflects a vaccine strategy as complementary to the existing control programs to combat different forms of schistosomiasis will be important to develop a vaccine effectively.

Worms, wisdom, and wealth: why deworming can make economic sense.

For those of us who have had worms, getting rid of them seems a good idea, and multiple studies demonstrate the simplicity and benefit of deworming children. In the past decade or so, there has been a dramatic increase in efforts to provide inexpensive deworming medications, but at the same time there have been calls to re-evaluate the impact of deworming programs. In this review, we examine the history of deworming and explore the evidence for effects of deworming on health, on child development, and on economic returns. Important policy conclusions include that a paucity of randomized trial data suggesting benefit does not equate to a lack of benefit and that a greater emphasis on documenting such benefit should be pursued.