Effects of geographic and economic heterogeneity on the burden of rotavirus diarrhea and the impact and cost-effectiveness of vaccination in Nigeria.

Child mortality from rotavirus gastroenteritis remains high in Nigeria, representing 14% of all rotavirus deaths worldwide. Here, we examine the potential impact and cost-effectiveness of national rotavirus vaccine introduction in geographic and economic subpopulations of Nigeria. We projected the health and economic outcomes of rotavirus vaccination in children over the first five years of life using a spreadsheet-based model. We modeled child populations using national survey data on rotavirus mortality risk factors and vaccination coverage to predict burden and impact across regional and wealth quintile subpopulations within Nigeria. Our base case considered introduction of a general rotavirus vaccine, modeled to encompass characteristics of existing vaccines, versus no vaccine. Base case costs were estimated from the government perspective, assuming Gavi subsidies, over the first five years. We also present estimates from the cost of vaccination from the perspective of Gavi. We explored uncertainty in model parameters through probabilistic uncertainty, one-way sensitivity, and scenario analyses. According to our estimates, rotavirus enteritis was responsible for 47,898 [95% Uncertainty Limits: 35,361; 63,703] child deaths per year, with approximately 80% of the national burden concentrated in the three northern regions of Nigeria. Rotavirus vaccination was estimated to prevent 6,454 [3,960; 9,721] deaths, 13% [9%; 18%] of the national annual RV burden. National ICERs for rotavirus vaccination from the Nigerian government and Gavi perspectives were US$47 [$18; $105] and $62 [$29; $130] per DALY averted, respectively. General rotavirus vaccination was projected to reduce rotavirus mortality by only 6% [4%; 9%] in the North West region compared to 35% [24%; 47%] in the South East region. Base case ICERs ranged from US$25 [10; 56] per DALY averted in North West to US$64 [18; 157] per DALY averted in South South. Gavi perspective ICERs ranged from US$33 [$15; $68] in North West to US$88 [35; 191] per DALY averted in South South. According to one-way sensitivity analyses, ICERs were most sensitive to vaccine efficacy, followed by estimated administrative costs and rotavirus mortality. Disparities in mortality reduction were largely driven by inequality in vaccination coverage across regions and between socioeconomic subpopulations. Due to high, persistent, and inequitable burden of rotavirus in Nigeria, routine vaccination with any of these rotavirus vaccines would be an high impact and cost-effective strategy in reducing child mortality.

Heterogeneity in enterotoxigenic Escherichia coli and shigella infections in children under 5 years of age from 11 African countries: a subnational approach quantifying risk, mortality, morbidity, and stunting.

BACKGROUND: Diarrhoea, a global cause of child mortality and morbidity, is linked to adverse consequences including childhood stunting and death from other diseases. Few studies explore how diarrhoeal mortality varies subnationally, especially by cause, which is important for targeting investments. Even fewer examine indirect effects of diarrhoeal morbidity on child mortality. We estimated the subnational distribution of mortality, morbidity, and childhood stunting attributable to enterotoxigenic Escherichia coli (ETEC) and shigella infection in children younger than 5 years from 11 eastern and central African countries. These pathogens are leading causes of diarrhoea in young children and have been linked to increased childhood stunting. METHODS: We combined proxy indicators of morbidity and mortality risk from the most recent Demographic and Health Surveys with published relative risks to estimate the potential distribution of diarrhoeal disease risk. To estimate subnational burden, we used country-specific or WHO region-specific morbidity and mortality estimates and distributed them subnationally by three indices that integrate relevant individual characteristics (ie, underweight, probability of receiving oral rehydration treatment of diarrhoea, and receiving vitamin A supplementation) and household characteristics (ie, type of drinking water and sanitation facilities). FINDINGS: Characterising ETEC and shigella subnational estimates of indirect morbidity (infection-attributable stunting) and indirect mortality (stunting-related deaths from other infectious diseases) identified high-risk areas that could be missed by traditional metrics. Burundi and Democratic Republic of the Congo had the highest ETEC-associated and shigella-associated mortality and stunting rates. Mozambique, Democratic Republic of the Congo, and Zimbabwe had the greatest subnational heterogeneity in most ETEC and shigella mortality measures. Inclusion of indirect ETEC and shigella mortality in burden estimates resulted in a 20-30% increase in total ETEC and shigella mortality rates in some subnational areas. INTERPRETATION: Understanding the indirect mortality and morbidity of diarrhoeal pathogens on a subnational level will strengthen disease control strategies and could have important implications for the relative impact and cost-effectiveness of new enteric vaccines. Because our methods rely on publicly available data, they could be employed for national planning. FUNDING: Bill & Melinda Gates Foundation.

Heterogeneity in potential impact and cost-effectiveness of ETEC and Shigella vaccination in four sub-Saharan African countries.

Diarrheal disease burden has become more heterogenous in low- and lower middle-income countries as access to clean water, sanitation and health care has increased in wealthier urban populations. Enterotoxigenic Escherichia coli (ETEC) and Shigella are among the top five causes of diarrheal mortality in children living in sub-Saharan Africa. Here, we explored how accounting for subnational and economic heterogeneity in ETEC and Shigella disease burden affects projected vaccine impact and cost-effectiveness of standalone ETEC and Shigella vaccines during the first decade after introduction in four sub-Saharan African countries. We developed dynamic models for provincial areas and socioeconomic subpopulations of children in the Democratic Republic of Congo (DRC), Kenya, Zambia, and Zimbabwe. We estimated deaths and morbidity due to ETEC and Shigella diarrhea plus additional deaths from other infectious diseases attributable to ETEC- and Shigella-induced stunting. We analyzed cost-effectiveness using Incremental Cost-Effectiveness Ratios (ICERs) with Disability-Adjusted Life Years (DALYs) and Moderate-and-Severe Diarrheal episodes (MSD) averted as denominators. Other infectious disease deaths due to induced stunting accounted for 9-28% and 9-32% of the total provincial level ETEC and Shigella disease burden, respectively, across these four countries from years 2025 to 2034. Our results indicated that the lowest and most cost-effective provincial DALYs averted ICERs were below $600 and $500/DALY averted for ETEC and Shigella vaccination, respectively in Zimbabwe. ICERs were the highest in Zambia and Kenya, where all provincial ICERs where above $2000/DALY. The highest national and provincial MSD averted ICERs were in DRC, while the lowest were in Kenya and Zimbabwe. Vaccinations were most cost-effective in averting DALYs in lower wealth subpopulations living in the highest burden provincial areas. Our approach focused on subnational heterogeneity in ETEC and Shigella burden and vaccination access found that impact and cost-effectiveness were more favorable if vaccinations reach the most vulnerable children in underserved provinces.

Potential impact and cost-effectiveness of future ETEC and Shigella vaccines in 79 low- and lower middle-income countries.

While diarrhea mortality in children has declined over the last two decades, there has been a slower decline in diarrheal episodes. Repeated diarrheal episodes are associated with childhood stunting, which leads to increased mortality risk from infectious diseases. Vaccine candidates are under development for enterotoxigenic Escherichia coli [ETEC] and Shigella, important enteric pathogens in children in low income countries. These future vaccines could significantly reduce diarrheal burden, prevent ETEC- and Shigella-induced stunting, and stunting-associated mortality. We developed a cost-effectiveness model for two putative standalone ETEC and Shigella vaccine candidates to evaluate vaccine impact on mortality, morbidity, stunting, and stunting-associated deaths from other infectious diseases. We modeled impact over the first ten years after vaccine introduction in children under five years old living in 79 low and low-middle income countries. ETEC and Shigella diarrhea would cause an estimated 239,300 [95% UL: 179,700-309,800] and 340,300 [256,500-440,800] child deaths, respectively, from years 2025 to 2034. Most of these deaths would occur in AFRO countries. ETEC and Shigella moderate-to-severe diarrheal episodes would result in over 13.7 [8.4-19.0] and 21.4 [13.1-29.8] million stunted children, respectively. Introducing ETEC or Shigella vaccine each with 60% efficacy could prevent 92,000 [61,000-129,000] ETEC and 126,600 [84,000-179,000] Shigella direct deaths and 21,400 [11,300-34,800] ETEC- and 34,200 [18,000-56,000] Shigella-induced stunting deaths. ETEC ICERs ranged from $2172/DALY [1457-4369] in AFRO to $19,172/DALY [12,665-39,503] in EURO. Shigella ICERs ranged from $952/DALY [632-2001] in EMRO to $640,316/DALY [434,311-1,297,192] in EURO. Limitations of this analysis include uncertainty of vaccine efficacy, duration of protection, and vaccine price. Inclusion of other infectious disease mortality due to stunting provides a more accurate assessment of total ETEC and Shigella disease burden and increased the projected impact and cost-effectiveness of vaccination. Introducing vaccines only in high burden countries and regions could substantially reduce cost without substantially reducing impact.

Household Costs of Diarrhea by Etiology in 7 Countries, The Global Enterics Mulitcenter Study (GEMS).

BACKGROUND: Although there are many overlapping features, pediatric diarrheal diseases can vary in severity, duration, clinical manifestations, and sequelae according to the causal pathogen, which in turn can impact the economic burden on patients and their families. We aimed to evaluate the household costs of diarrheal disease by pathogen in 7 countries. METHODS: We analyzed data from the Global Enteric Multicenter Study (GEMS), a prospective, age-stratified, matched case-control study of moderate to severe diarrheal disease among children aged 0-59 months in 7 low-income countries; 4 in Africa (Kenya, Mali, Mozambique, The Gambia) and 3 in Asia (Bangladesh, India, Pakistan). Demographic, epidemiological, economic, and clinical data were collected, and a stool sample was obtained for microbiological analysis at enrollment. We used a multivariate generalized linear model to assess the effect of rotavirus, Cryptosporidium, heat-stable toxin (ST)-producing enterotoxigenic Escherichia coli (ETEC [ST only or LT plus ST]), Shigella, Campylobacter jejuni, norovirus GII, Vibrio cholerae O1, age, gender, in/outpatient, and country on total costs to the patient/family. RESULTS: Household out-of-pocket costs were higher in Mali than any other country. Within countries, household cost differences between pathogens were minimal and not statistically significantly different. CONCLUSIONS: We found no significant differences in household costs by pathogen. Despite data limitations, understanding pathogen-specific household costs (or lack thereof) is useful, as decision-makers could consider broader illness cost information and its relevance to a particular pathogen's economic burden and contribution to poverty when deciding which pathogens to target for interventions.

Burden of enterotoxigenic Escherichia coli and shigella non-fatal diarrhoeal infections in 79 low-income and lower middle-income countries: a modelling analysis.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) and shigella are two major pathogens that cause moderate-to-severe diarrhoea in children younger than 5 years. Diarrhoea is associated with an increased risk of stunting, which puts children at risk of death due to other infectious diseases. METHODS: We modelled ETEC-related and shigella-related mortality and the effect of moderate-to-severe diarrhoea episodes to determine the number of children with stunting due to these infections in 79 low-income and lower middle-income countries. We applied population attributable risk for increased number of deaths due to other infectious diseases in children who are stunted. We calculated 95% uncertainty intervals (UIs) for the point estimates. FINDINGS: In children younger than 5 years, we estimate 196 million (95% UI 135-269) episodes of ETEC and shigella diarrhoea occur annually, resulting in 3·5 million (0·8-5·4) cases of moderate-to-severe stunting and 44 400 (29 400-59 800) total ETEC deaths and 63 100 (44 000-81 900) total shigella deaths in 2015. Additional infectious disease mortality due to stunting resulted in increases of 24% (8-34; for ETEC) and 28% (10-39; for shigella) over direct deaths due to diarrhoeal episodes. The distribution of mortality and morbidity varied geographically, with African Region and Eastern Mediterranean Region countries bearing the greatest burden. INTERPRETATION: The expanded effects of non-fatal ETEC and shigella-related diarrhoeal episodes can have lasting consequences. Prevention of these infections could reduce the risk of direct death and stunting and deaths due to other infectious diseases. Understanding the countries and populations with the highest disease risk helps to target interventions for the most vulnerable populations. FUNDING: The Bill & Melinda Gates Foundation.

Effects of geographic and economic heterogeneity on the burden of rotavirus diarrhea and the impact and cost-effectiveness of vaccination in Pakistan.

Globally, rotavirus is a leading cause of childhood diarrhea and related mortality. Although rotavirus vaccination has been introduced in many countries worldwide, there are numerous low- to middle-income countries that have not yet introduced. Pakistan is one of the countries with the highest number of rotavirus deaths in children under five years. Although rotavirus infection is almost universal among children, mortality is often a result of poor nutrition and lack of access to health care and other aspects of poverty. We assess the impact and cost-effectiveness of introducing childhood rotavirus vaccination in Pakistan. We use household data from the 2012-2013 Demographic Health survey in Pakistan to estimate heterogeneity in rotavirus mortality risk, vaccination benefits, and cost-effectiveness across geographic and economic groups. We estimate two-dose rotavirus vaccination coverage that would be distributed through a routine vaccination program. In addition, we estimate rotavirus mortality (burden), and other measures of vaccine cost-effectiveness and impact by subpopulations of children aggregated by region and economic status. Results indicate that the highest estimated regional rotavirus burden is in Sindh (3.3 rotavirus deaths/1000 births) and Balochistan (3.1 rotavirus deaths/1000 births), which also have the lowest estimated vaccination coverage, particularly for children living in the poorest households. In Pakistan, introduction could prevent 3061 deaths per year with current routine immunization patterns at an estimated $279/DALY averted. Increases in coverage to match the region with highest coverage (Islamabad) could prevent an additional 1648 deaths per year. Vaccination of children in the highest risk regions could result in a fourfold mortality reduction as compared to low risk children, and children in the poorest households have a three to four times greater mortality reduction benefit than the richest. Based on the analysis presented here, the benefits and cost-effectiveness of rotavirus vaccination can be maximized by reaching economically and geographically vulnerable children.

Effects of geographic and economic heterogeneity on rotavirus diarrhea burden and vaccination impact and cost-effectiveness in the Lao People's Democratic Republic.

Rotavirus enteritis is responsible for nearly 200,000 child deaths worldwide in 2015. Globally, many low- and middle-income countries have introduced rotavirus vaccine, resulting in documented reductions in hospitalizations and child mortality. We examined the potential impact and cost-effectiveness of introducing rotavirus vaccination in Lao People's Democratic Republic using an Excel-based spreadsheet model. We estimated mortality risk factors, patterns of care seeking, and vaccination access to predict outcomes for regional, provincial, and socioeconomic subpopulations for one birth cohort through their first five years of life and life course in Disability-Adjusted Life Years estimates. Socioeconomic status was defined by categorizing households into regional wealth quintiles based on a national asset index. We modeled a two-dose ROTARIX vaccine under current Gavi pricing and efficacy estimates from Bangladesh and Vietnam. DPT1 and DPT2 coverages were used to estimate rotavirus vaccination coverage. Probabilistic sensitivity analysis was used to assess the impact of uncertainty on model parameters on predicted incremental cost-effectiveness ratios (ICERs), including scenarios of increases in vaccination coverage. Rotavirus vaccination would prevent 143 child deaths/year, or 28% of annual rotavirus burden. The estimated national level ICER for rotavirus vaccination was $140/DALY, with regional socioeconomic subpopulation estimates ranging from $72/DALY for the poorest in the Central region to $353/DALY for the richest in the North region, indicating high cost-effectiveness. Within regions, ICERs are most favorable for children in the poorer and poorest quintiles. However, the full benefits of rotavirus vaccination will only be realized by reducing disparities in vaccination coverage, access to treatment, and environmental health. Improving vaccination coverage to equitable levels alone would prevent 87 additional child deaths per year.

The effect of costs on Kenyan households' demand for medical care: why time and distance matter.

In an environment of constrained resources, policymakers must identify solutions for financing and delivering health services that are efficient and sustainable. However, such solutions require that policymakers understand the complex interaction between household utilization patterns, factors influencing household medical decisions, and provider performance. This study examined whether and under what conditions out-of-pocket, transportation, and time costs influenced Kenyan households' choice of medical provider for childhood diarrhoeal illnesses. It compared these decisions with the actual cost and quality of those providers to assess strategies for increasing the utilization of high quality, low-cost primary care. This study analyzed nationally-representative survey data through several multinomial nested logit models. On average, time costs accounted for the greatest share of total costs. Households spent the most time and transportation costs utilizing public care, yet were more likely to incur catastrophic time and out-of-pocket costs seeking private care for their child's diarrhoeal illness. Out-of-pocket, transportation, and time costs influenced households' choice of provider, though demand was cost inelastic and households were most responsive to transportation costs. Poorer households were the most responsive to changes in all cost types and most likely to self-treat or utilize informal care. Many households utilized informal care that, relative to formal care, cost the same but was of worse quality-suggesting that such households were making poor medical decisions for their children. To achieve public policy objectives, such as financial risk protection for childhood illnesses and equitable access to primary care, policymakers could focus on three areas: (1) refine financing strategies for further reducing household out-of-pocket costs; (2) reduce or subsidize time and transportation costs for households seeking public and private care; and (3) increase transparency of costs and quality to improve household decisions.

Cost-effectiveness of maternal influenza immunization in Bamako, Mali: A decision analysis.

BACKGROUND: Maternal influenza immunization has gained traction as a strategy to diminish maternal and neonatal mortality. However, efforts to vaccinate pregnant women against influenza in developing countries will require substantial investment. We present cost-effectiveness estimates of maternal influenza immunization based on clinical trial data from Bamako, Mali. METHODS: We parameterized a decision-tree model using prospectively collected trial data on influenza incidence, vaccine efficacy, and direct and indirect influenza-related healthcare expenditures. Since clinical trial participants likely had better access to care than the general Malian population, we also simulated scenarios with poor access to care, including decreased healthcare resource utilization and worse influenza-related outcomes. RESULTS: Under base-case assumptions, a maternal influenza immunization program in Mali would cost $857 (95% UI: $188-$2358) per disability-adjusted life year (DALY) saved. Adjusting for poor access to care yielded a cost-effectiveness ratio of $486 (95% UI: $105-$1425) per DALY saved. Cost-effectiveness ratios were most sensitive to changes in the cost of a maternal vaccination program and to the proportion of laboratory-confirmed influenza among infants warranting hospitalization. Mean cost-effectiveness estimates fell below Mali's GDP per capita when the cost per pregnant woman vaccinated was $1.00 or less with no adjustment for access to care or $1.67 for those with poor access to care. Healthcare expenditures for lab-confirmed influenza were not significantly different than the cost of influenza-like illness. CONCLUSIONS: Maternal influenza immunization in Mali would be cost-effective in most settings if vaccine can be obtained, managed, and administered for ≤$1.00 per pregnant woman.

Determinants of quality of shared sanitation facilities in informal settlements: case study of Kisumu, Kenya.

BACKGROUND: Shared facilities are not recognised as improved sanitation due to challenges of maintenance as they easily can be avenues for the spread of diseases. Thus there is need to evaluate the quality of shared facilities, especially in informal settlements, where they are commonly used. A shared facility can be equated to a common good whose management depends on the users. If users do not work collectively towards keeping the facility clean, it is likely that the quality may depreciate due to lack of maintenance. This study examined the quality of shared sanitation facilities and used the common pool resource (CPR) management principles to examine the determinants of shared sanitation quality in the informal settlements of Kisumu, Kenya. METHODS: Using a multiple case study design, the study employed both quantitative and qualitative methods. In both phases, users of shared sanitation facilities were interviewed, while shared sanitation facilities were inspected. Shared sanitation quality was a score which was the dependent variable in a regression analysis. Interviews during the qualitative stage were aimed at understanding management practices of shared sanitation users. Qualitative data was analysed thematically by following the CPR principles. RESULTS: Shared facilities, most of which were dirty, were shared by an average of eight households, and their quality decreased with an increase in the number of households sharing. The effect of numbers on quality is explained by behaviour reflected in the CPR principles, as it was easier to define boundaries of shared facilities when there were fewer users who cooperated towards improving their shared sanitation facility. Other factors, such as defined management systems, cooperation, collective decision making, and social norms, also played a role in influencing the behaviour of users towards keeping shared facilities clean and functional. CONCLUSION: Apart from hardware factors, quality of shared sanitation is largely due to group behaviour of users. The CPR principles form a crucial lens through which the dynamics of shared sanitation facilities in informal settlements can be understood. Development and policy efforts should incorporate group behaviour as they determine the quality of shared sanitation facilities.

Estimating the Cost and Payment for Sanitation in the Informal Settlements of Kisumu, Kenya: A Cross Sectional Study.

Lack of sanitation facilities is a common occurrence in informal settlements that are common in most developing countries. One challenge with sanitation provision in these settlements is the cost and financing of sanitation. This study aimed at estimating the cost of sanitation, and investigating the social and economic dynamics within Kisumu's informal settlements that hinder provision and uptake of sanitation facilities. Primary data was collected from residents of the settlements, and using logistic and hedonic regression analysis, we identify characteristics of residents with sanitation facilities, and estimate the cost of sanitation as revealed in rental prices. Our study finds that sanitation constitutes approximately 54% of the rent paid in the settlements; and dynamics such as landlords and tenants preferences, and sharing of sanitation facilities influence provision and payment for sanitation. This study contributes to general development by estimating the cost of sanitation, and further identifies barriers and opportunities for improvement including the interplay between landlords and tenants. Provision of sanitation in informal settlements is intertwined in social and economic dynamics, and development approaches should target both landlords and tenants, while also engaging various stakeholders to work together to identify affordable and appropriate sanitation technologies.

Correction: High-Resolution Spatial Distribution and Estimation of Access to Improved Sanitation in Kenya.

[This corrects the article DOI: 10.1371/journal.pone.0158490.].

Correction: High-Resolution Spatial Distribution and Estimation of Access to Improved Sanitation in Kenya.

[This corrects the article DOI: 10.1371/journal.pone.0158490.].

High-Resolution Spatial Distribution and Estimation of Access to Improved Sanitation in Kenya.

BACKGROUND: Access to sanitation facilities is imperative in reducing the risk of multiple adverse health outcomes. A distinct disparity in sanitation exists among different wealth levels in many low-income countries, which may hinder the progress across each of the Millennium Development Goals. METHODS: The surveyed households in 397 clusters from 2008-2009 Kenya Demographic and Health Surveys were divided into five wealth quintiles based on their national asset scores. A series of spatial analysis methods including excess risk, local spatial autocorrelation, and spatial interpolation were applied to observe disparities in coverage of improved sanitation among different wealth categories. The total number of the population with improved sanitation was estimated by interpolating, time-adjusting, and multiplying the surveyed coverage rates by high-resolution population grids. A comparison was then made with the annual estimates from United Nations Population Division and World Health Organization /United Nations Children's Fund Joint Monitoring Program for Water Supply and Sanitation. RESULTS: The Empirical Bayesian Kriging interpolation produced minimal root mean squared error for all clusters and five quintiles while predicting the raw and spatial coverage rates of improved sanitation. The coverage in southern regions was generally higher than in the north and east, and the coverage in the south decreased from Nairobi in all directions, while Nyanza and North Eastern Province had relatively poor coverage. The general clustering trend of high and low sanitation improvement among surveyed clusters was confirmed after spatial smoothing. CONCLUSIONS: There exists an apparent disparity in sanitation among different wealth categories across Kenya and spatially smoothed coverage rates resulted in a closer estimation of the available statistics than raw coverage rates. Future intervention activities need to be tailored for both different wealth categories and nationally where there are areas of greater needs when resources are limited.

A controlled, before-and-after trial of an urban sanitation intervention to reduce enteric infections in children: research protocol for the Maputo Sanitation (MapSan) study, Mozambique.

INTRODUCTION: Access to safe sanitation in low-income, informal settlements of Sub-Saharan Africa has not significantly improved since 1990. The combination of a high faecal-related disease burden and inadequate infrastructure suggests that investment in expanding sanitation access in densely populated urban slums can yield important public health gains. No rigorous, controlled intervention studies have evaluated the health effects of decentralised (non-sewerage) sanitation in an informal urban setting, despite the role that such technologies will likely play in scaling up access. METHODS AND ANALYSIS: We have designed a controlled, before-and-after (CBA) trial to estimate the health impacts of an urban sanitation intervention in informal neighbourhoods of Maputo, Mozambique, including an assessment of whether exposures and health outcomes vary by localised population density. The intervention consists of private pour-flush latrines (to septic tank) shared by multiple households in compounds or household clusters. We will measure objective health outcomes in approximately 760 children (380 children with household access to interventions, 380 matched controls using existing shared private latrines in poor sanitary conditions), at 2 time points: immediately before the intervention and at follow-up after 12 months. The primary outcome is combined prevalence of selected enteric infections among children under 5 years of age. Secondary outcome measures include soil-transmitted helminth (STH) reinfection in children following baseline deworming and prevalence of reported diarrhoeal disease. We will use exposure assessment, faecal source tracking, and microbial transmission modelling to examine whether and how routes of exposure for diarrhoeagenic pathogens and STHs change following introduction of effective sanitation. ETHICS: Study protocols have been reviewed and approved by human subjects review boards at the London School of Hygiene and Tropical Medicine, the Georgia Institute of Technology, the University of North Carolina at Chapel Hill, and the Ministry of Health, Republic of Mozambique. TRIAL REGISTRATION NUMBER: NCT02362932.

Shamba Maisha: Pilot agricultural intervention for food security and HIV health outcomes in Kenya: design, methods, baseline results and process evaluation of a cluster-randomized controlled trial.

BACKGROUND: Despite advances in treatment of people living with HIV, morbidity and mortality remains unacceptably high in sub-Saharan Africa, largely due to parallel epidemics of poverty and food insecurity. METHODS/DESIGN: We conducted a pilot cluster randomized controlled trial (RCT) of a multisectoral agricultural and microfinance intervention (entitled Shamba Maisha) designed to improve food security, household wealth, HIV clinical outcomes and women's empowerment. The intervention was carried out at two HIV clinics in Kenya, one randomized to the intervention arm and one to the control arm. HIV-infected patients >18 years, on antiretroviral therapy, with moderate/severe food insecurity and/or body mass index (BMI) <18.5, and access to land and surface water were eligible for enrollment. The intervention included: 1) a microfinance loan (~$150) to purchase the farming commodities, 2) a micro-irrigation pump, seeds, and fertilizer, and 3) trainings in sustainable agricultural practices and financial literacy. Enrollment of 140 participants took four months, and the screening-to-enrollment ratio was similar between arms. We followed participants for 12 months and conducted structured questionnaires. We also conducted a process evaluation with participants and stakeholders 3-5 months after study start and at study end. DISCUSSION: Baseline results revealed that participants at the two sites were similar in age, gender and marital status. A greater proportion of participants at the intervention site had a low BMI in comparison to participants at the control site (18% vs. 7%, p = 0.054). While median CD4 count was similar between arms, a greater proportion of participants enrolled at the intervention arm had a detectable HIV viral load compared with control participants (49% vs. 28%, respectively, p < 0.010). Process evaluation findings suggested that Shamba Maisha had high acceptability in recruitment, delivered strong agricultural and financial training, and led to labor saving due to use of the water pump. Implementation challenges included participant concerns about repaying loans, agricultural challenges due to weather patterns, and a challenging partnership with the microfinance institution. We expect the results from this pilot study to provide useful data on the impacts of livelihood interventions and will help in the design of a definitive cluster RCT. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT01548599.

Factors associated with pupil toilet use in kenyan primary schools.

The purpose of this study was to quantify how school sanitation conditions are associated with pupils' use of sanitation facilities. We conducted a longitudinal assessment in 60 primary schools in Nyanza Province, Kenya, using structured observations to measure facility conditions and pupils' use at specific facilities. We used multivariable mixed regression models to characterize how pupil to toilet ratio was associated with toilet use at the school-level and also how facility conditions were associated with pupils' use at specific facilities. We found a piecewise linear relationship between decreasing pupil to toilet ratio and increasing pupil toilet use (p < 0.01). Our data also revealed significant associations between toilet use and newer facility age (p < 0.01), facility type (p < 0.01), and the number of toilets in a facility (p < 0.01). We found some evidence suggesting facility dirtiness may deter girls from use (p = 0.06), but not boys (p = 0.98). Our study is the first to rigorously quantify many of these relationships, and provides insight into the complexity of factors affecting pupil toilet use patterns, potentially leading to a better allocation of resources for school sanitation, and to improved health and educational outcomes for children.

Estimated impact and cost-effectiveness of rotavirus vaccination in India: effects of geographic and economic disparities.

India accounts for 23% of global rotavirus mortality in under-five children, with more than 100,000 deaths from rotavirus annually. Introduction of a vaccine in India is considered to be the most effective intervention for preventing rotavirus mortality. Recent research suggests that there is considerable variation in rotavirus mortality burden across regional, gender and socio-economic subpopulations within India. In addition, there is potential variability in who would likely receive rotavirus vaccine if introduced. We use available household data to estimate heterogeneity in rotavirus mortality risk, vaccination benefits, and cost-effectiveness across geographic and socio-economic groups within India. We account for heterogeneity by modeling estimated three-dose routine vaccinations as a proxy for a generalized rotavirus vaccine, and mortality for subpopulations of children aggregated by region and state, socio-economic status and sex, separately. Results are presented for six geographic regions and for Bihar, Uttar Pradesh, and Madhya Pradesh, three high mortality states accounting for 56% of national mortality estimates. Impact estimates accounting for disparities predict rotavirus vaccine introduction will prevent 35,000 deaths at an average cost of $118/DALY averted (7292 INR/DALY averted). Rotavirus vaccines are most cost-effective for the poor living in high mortality regions and states. Reductions in geographic and socio-economic disparities based on regional estimates could prevent an additional 9400 deaths annually, while reductions in socio-economic disparities in the three highest morality states alone could prevent an additional 10,600 deaths annually. Understanding the impact of heterogeneity can help improve strategies to maximize the benefits of rotavirus vaccination introduction, leading to fewer lives lost as a result of rotavirus disease.

Assessing the impact of a school-based latrine cleaning and handwashing program on pupil absence in Nyanza Province, Kenya: a cluster-randomized trial.

OBJECTIVES: Improving school water, sanitation and hygiene (WASH) conditions reduces pupil absence and illness. However, these benefits may depend on the conditions of the latrines and availability of consumables. We sought to determine whether a low-cost, policy-relevant, environmental-level latrine cleaning intervention could improve latrine cleanliness, increase its use and reduce absenteeism. METHODS: In a three-arm, cluster-randomized trial we assessed absence via periodical roll-call among 17 564 pupils in 60 schools that had previously received WASH improvements as part of the SWASH+ project. Latrine conditions and use were also assessed using structured observation. Latrine cleanliness increased significantly during the post-intervention period among schools receiving the latrine cleaning package compared to controls, as did handwashing with soap. We found no difference in latrine use and absence across arms. CONCLUSIONS: The additive impact of cleaning may not have been strong enough to impact absence above and beyond reductions attributable to the original WASH infrastructure improvements and basic hygiene education the schools previously received. Improving latrine conditions is important for the dignity and well-being of pupils, and investments and strategies are necessary to ensure that school toilets are clean and pupil-friendly.