A Combined Dietary and Cognitive Intervention in 3⁻5-Year-Old Children in Indonesia: A Randomized Controlled Trial.

Early childhood nutritional interventions typically combine nutritional and psychosocial stimulation. Such combined interventions result in long-lasting improvements of cognitive abilities in children who are malnourished. Here, we investigated potential cognitive abilities in normally developing children in Indonesia who were, however, at risk for suboptimal cognitive development due to little psychosocial stimulation in their home environment. In a randomized controlled intervention, children of the experimental group received nutritional supplementation combined with cognitive stimulation. Pre- and post-intervention measurements included cognitive development and functioning, behavior, and mother⁻child interaction. The experimental and control group received nutritional supplementation in the form of a fortified or unfortified milk powder, respectively. Additionally, the children and parents of the experimental group jointly engaged in daily learning activities at home and performed iPad-based tasks designed to foster cognitive abilities. The experimental group compared to the control group displayed a significantly higher increase in intelligence quotient as well as a significantly larger reduction in attentional problems after the intervention. These results indicate that low-level cognitive stimulation in combination with nutritional supplementation during early childhood can be an effective intervention that improves global cognitive functioning in healthy developing children. ClinicalTrials.gov Identifier: NCT02359669.

Improvement of cardiometabolic markers after fish oil intervention in young Mexican adults and the role of PPARα L162V and PPARγ2 P12A.

Polyunsaturated fatty acids (PUFA) contained in fish oil (FO) are ligands for peroxisome proliferator-activated receptors (PPAR) that may induce changes in cardiometabolic markers. Variation in PPAR genes may influence the beneficial responses linked to FO supplementation in young adults. The study aimed to analyze the effect of FO supplementation on glucose metabolism, circulating lipids and inflammation according to PPARα L162V and PPARγ2 P12A genotypes in young Mexican adults. 191 young, non-smoking subjects between 18 and 40 years were included in a one-arm study. Participants were supplemented with 2.7 g/day of EPA+DHA, during six weeks. Dietary analysis, body composition measurements and indicators for glucose metabolism, circulating lipids, and markers for inflammation were analyzed before and after intervention. An overall decrease in triglycerides (TG) and an increase in HS-ω3 index were observed in all subjects [-4.1 mg/dL, (SD:±51.7), P=.02 and 2.6%, (SD:±1.2), P<.001 respectively]. Mean fasting insulin and glycated hemoglobin (HbA1c%) were significantly decreased in all subjects [-0.547mlU/L, (SD:±10.29), P=.034 and-0.07%, (SD:±0.3), P<.001 respectively], whereas there was no change in body composition, fasting glucose, adiponectin and inflammatory markers. Subjects carrying the minor alleles of PPARα L162V and PPARγ2 P12A had higher responses in reduction of TG and fasting insulin respectively. Interestingly, doses below 2.7 g/day (1.8 g/day) were sufficient to induce a significant reduction in fasting insulin and HbA1c% from baseline (P=.019 and P<.001). The observed responses in triglycerides and fasting insulin in the Mexican population give further evidence of the importance of FO supplementation in young people as an early step towards the prevention of cardiometabolic disease.

Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity: A Randomized Multicenter Trial.

OBJECTIVES: The aim of the study was to evaluate the effects of infant formula supplemented with 2 human milk oligosaccharides (HMOs) on infant growth, tolerance, and morbidity. METHODS: Healthy infants, 0 to 14 days old, were randomized to an intact-protein, cow's milk-based infant formula (control, n = 87) or the same formula with 1.0 g/L 2'fucosyllactose (2'FL) and 0.5 g/L lacto-N-neotetraose (LNnT) (test, n = 88) from enrollment to 6 months; all infants received standard follow-up formula without HMOs from 6 to 12 months. Primary endpoint was weight gain through 4 months. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, behavioral patterns, and morbidity through age 12 months. RESULTS: Weight gain was similar in both groups (mean difference [95% confidence interval] test vs control: -0.30 [-1.94, 1.34] g/day; lower bound of 95% confidence interval was above noninferiority margin [-3 g/day]). Digestive symptoms and behavioral patterns were similar between groups; exceptions included softer stool (P = 0.021) and fewer nighttime wake-ups (P = 0.036) in the test group at 2 months. Infants receiving test (vs control) had significantly fewer parental reports (P = 0.004-0.047) of bronchitis through 4 (2.3% vs 12.6%), 6 (6.8% vs 21.8%), and 12 months (10.2% vs 27.6%); lower respiratory tract infection (adverse event cluster) through 12 months (19.3% vs 34.5%); antipyretics use through 4 months (15.9% vs 29.9%); and antibiotics use through 6 (34.1% vs 49.4%) and 12 months (42.0% vs 60.9%). CONCLUSIONS: Infant formula with 2'FL and LNnT is safe, well-tolerated, and supports age-appropriate growth. Secondary outcome findings showing associations between consuming HMO-supplemented formula and lower parent-reported morbidity (particularly bronchitis) and medication use (antipyretics and antibiotics) warrant confirmation in future studies.

Predictive risk mapping of schistosomiasis in Brazil using Bayesian geostatistical models.

Schistosomiasis is one of the most common parasitic diseases in tropical and subtropical areas, including Brazil. A national control programme was initiated in Brazil in the mid-1970s and proved successful in terms of morbidity control, as the number of cases with hepato-splenic involvement was reduced significantly. To consolidate control and move towards elimination, there is a need for reliable maps on the spatial distribution of schistosomiasis, so that interventions can target communities at highest risk. The purpose of this study was to map the distribution of Schistosoma mansoni in Brazil. We utilized readily available prevalence data from the national schistosomiasis control programme for the years 2005-2009, derived remotely sensed climatic and environmental data and obtained socioeconomic data from various sources. Data were collated into a geographical information system and Bayesian geostatistical models were developed. Model-based maps identified important risk factors related to the transmission of S. mansoni and confirmed that environmental variables are closely associated with indices of poverty. Our smoothed predictive risk map, including uncertainty, highlights priority areas for intervention, namely the northern parts of North and Southeast regions and the eastern part of Northeast region. Our predictive risk map provides a useful tool for to strengthen existing surveillance-response mechanisms.

Spatio-temporal malaria transmission patterns in Navrongo demographic surveillance site, northern Ghana.

BACKGROUND: The relationship between entomological measures of malaria transmission intensity and mortality remains uncertain. This is partly because transmission is heterogeneous even within small geographical areas. Studying this relationship requires high resolution, spatially structured, longitudinal entomological data. Geostatistical models that have been used to analyse the spatio-temporal heterogeneity have not considered the uncertainty in both sporozoite rate (SR) and mosquito density data. This study analysed data from Kassena-Nankana districts in northern Ghana to obtain small area estimates of malaria transmission rates allowing for this uncertainty. METHODS: Independent Bayesian geostatistical models for sporozoite rate and mosquito density were fitted to produce explicit entomological inoculation rate (EIR) estimates for small areas and short time periods, controlling for environmental factors. RESULTS: Mosquitoes were trapped from 2,803 unique locations for three years using mainly CDC light traps. Anopheles gambiae constituted 52%, the rest were Anopheles funestus. Mean biting rates for An. funestus and An. gambiae were 32 and 33 respectively. Most bites occurred in September, the wettest month. The sporozoite rates were higher in the dry periods of the last two years compared with the wet period. The annual EIR varied from 1,132 to 157 infective bites. Monthly EIR varied between zero and 388 infective bites. Spatial correlation for SR was lower than that of mosquito densities. CONCLUSION: This study confirms the presence of spatio-temporal heterogeneity in malaria transmission within a small geographical area. Spatial variance was stronger than temporal especially in the SR. The estimated EIR will be used in mortality analysis for the area.

Micro-scale investigation of intestinal schistosomiasis transmission on Ngamba and Kimi islands, Lake Victoria, Uganda.

A study to investigate the effect of environmental predictors on abundance of Biomphalaria, the intermediate host snails of Schistosoma mansoni, was carried out on two small islands in Lake Victoria, Uganda. Malacological surveys were performed at 40 shoreline sites on Kimi and Ngamba islands documenting occurrence of Biomphalaria; other environmental and limnological conditions were also recorded, including gastropod community diversity. Snails were examined for shedding of schistosomes and emerging cercariae were DNA 'barcoded'. For population genetics analysis of Biomphalaria, snails from four populations from each island were also sequenced. Aquatic phosphate concentrations were higher on Kimi island, confirming greater anthropogenic influence, although, snail species diversity and community assemblages were not significantly different between islands. Bayesian geostatistical models were fitted to assess the effect of environmental factors on Biomphalaria abundance and snails' risk of shedding schistosome or non-schistosome cercariae. No factors were found to be significant in the spatial model. The local population genetics of S. mansoni and Biomphalaria on each island followed similar patterns as that seen in previous studies on a lake-wide basis. These findings suggest that smaller scale studies may prove useful as proxies for regional level investigations, with reduced logistical and resource output required. However, further research should also include surveys of terminal host parasite burden, as these will affect even micro-scale dynamics of parasite-intermediate host interactions, as well as be important from a public health perspective in their own right.

Spatially explicit burden estimates of malaria in Tanzania: bayesian geostatistical modeling of the malaria indicator survey data.

A national HIV/AIDS and malaria parasitological survey was carried out in Tanzania in 2007-2008. In this study the parasitological data were analyzed: i) to identify climatic/environmental, socio-economic and interventions factors associated with child malaria risk and ii) to produce a contemporary, high spatial resolution parasitaemia risk map of the country. Bayesian geostatistical models were fitted to assess the association between parasitaemia risk and its determinants. bayesian kriging was employed to predict malaria risk at unsampled locations across Tanzania and to obtain the uncertainty associated with the predictions. Markov chain Monte Carlo (MCMC) simulation methods were employed for model fit and prediction. Parasitaemia risk estimates were linked to population data and the number of infected children at province level was calculated. Model validation indicated a high predictive ability of the geostatistical model, with 60.00% of the test locations within the 95% credible interval. The results indicate that older children are significantly more likely to test positive for malaria compared with younger children and living in urban areas and better-off households reduces the risk of infection. However, none of the environmental and climatic proxies or the intervention measures were significantly associated with the risk of parasitaemia. Low levels of malaria prevalence were estimated for Zanzibar island. The population-adjusted prevalence ranges from 0.29% in Kaskazini province (Zanzibar island) to 18.65% in Mtwara region. The pattern of predicted malaria risk is similar with the previous maps based on historical data, although the estimates are lower. The predicted maps could be used by decision-makers to allocate resources and target interventions in the regions with highest burden of malaria in order to reduce the disease transmission in the country.

Estimating the burden of malaria in Senegal: Bayesian zero-inflated binomial geostatistical modeling of the MIS 2008 data.

The Research Center for Human Development in Dakar (CRDH) with the technical assistance of ICF Macro and the National Malaria Control Programme (NMCP) conducted in 2008/2009 the Senegal Malaria Indicator Survey (SMIS), the first nationally representative household survey collecting parasitological data and malaria-related indicators. In this paper, we present spatially explicit parasitaemia risk estimates and number of infected children below 5 years. Geostatistical Zero-Inflated Binomial models (ZIB) were developed to take into account the large number of zero-prevalence survey locations (70%) in the data. Bayesian variable selection methods were incorporated within a geostatistical framework in order to choose the best set of environmental and climatic covariates associated with the parasitaemia risk. Model validation confirmed that the ZIB model had a better predictive ability than the standard Binomial analogue. Markov chain Monte Carlo (MCMC) methods were used for inference. Several insecticide treated nets (ITN) coverage indicators were calculated to assess the effectiveness of interventions. After adjusting for climatic and socio-economic factors, the presence of at least one ITN per every two household members and living in urban areas reduced the odds of parasitaemia by 86% and 81% respectively. Posterior estimates of the ORs related to the wealth index show a decreasing trend with the quintiles. Infection odds appear to be increasing with age. The population-adjusted prevalence ranges from 0.12% in Thillé-Boubacar to 13.1% in Dabo. Tambacounda has the highest population-adjusted predicted prevalence (8.08%) whereas the region with the highest estimated number of infected children under the age of 5 years is Kolda (13940). The contemporary map and estimates of malaria burden identify the priority areas for future control interventions and provide baseline information for monitoring and evaluation. Zero-Inflated formulations are more appropriate in modeling sparse geostatistical survey data, expected to arise more frequently as malaria research is focused on elimination.

Bayesian geostatistical modeling of Malaria Indicator Survey data in Angola.

The 2006-2007 Angola Malaria Indicator Survey (AMIS) is the first nationally representative household survey in the country assessing coverage of the key malaria control interventions and measuring malaria-related burden among children under 5 years of age. In this paper, the Angolan MIS data were analyzed to produce the first smooth map of parasitaemia prevalence based on contemporary nationwide empirical data in the country. Bayesian geostatistical models were fitted to assess the effect of interventions after adjusting for environmental, climatic and socio-economic factors. Non-linear relationships between parasitaemia risk and environmental predictors were modeled by categorizing the covariates and by employing two non-parametric approaches, the B-splines and the P-splines. The results of the model validation showed that the categorical model was able to better capture the relationship between parasitaemia prevalence and the environmental factors. Model fit and prediction were handled within a Bayesian framework using Markov chain Monte Carlo (MCMC) simulations. Combining estimates of parasitaemia prevalence with the number of children under we obtained estimates of the number of infected children in the country. The population-adjusted prevalence ranges from in Namibe province to in Malanje province. The odds of parasitaemia in children living in a household with at least ITNs per person was by 41% lower (CI: 14%, 60%) than in those with fewer ITNs. The estimates of the number of parasitaemic children produced in this paper are important for planning and implementing malaria control interventions and for monitoring the impact of prevention and control activities.

Geographical patterns and predictors of malaria risk in Zambia: Bayesian geostatistical modelling of the 2006 Zambia national malaria indicator survey (ZMIS).

BACKGROUND: The Zambia Malaria Indicator Survey (ZMIS) of 2006 was the first nation-wide malaria survey, which combined parasitological data with other malaria indicators such as net use, indoor residual spraying and household related aspects. The survey was carried out by the Zambian Ministry of Health and partners with the objective of estimating the coverage of interventions and malaria related burden in children less than five years. In this study, the ZMIS data were analysed in order (i) to estimate an empirical high-resolution parasitological risk map in the country and (ii) to assess the relation between malaria interventions and parasitaemia risk after adjusting for environmental and socio-economic confounders. METHODS: The parasitological risk was predicted from Bayesian geostatistical and spatially independent models relating parasitaemia risk and environmental/climatic predictors of malaria. A number of models were fitted to capture the (potential) non-linearity in the malaria-environment relation and to identify the elapsing time between environmental effects and parasitaemia risk. These models included covariates (a) in categorical scales and (b) in penalized and basis splines terms. Different model validation methods were used to identify the best fitting model. Model-based risk predictions at unobserved locations were obtained via Bayesian predictive distributions for the best fitting model. RESULTS: Model validation indicated that linear environmental predictors were able to fit the data as well as or even better than more complex non-linear terms and that the data do not support spatial dependence. Overall the averaged population-adjusted parasitaemia risk was 20.0% in children less than five years with the highest risk predicted in the northern (38.3%) province. The odds of parasitaemia in children living in a household with at least one bed net decreases by 40% (CI: 12%, 61%) compared to those without bed nets. CONCLUSIONS: The map of parasitaemia risk together with the prediction error and the population at risk give an important overview of the malaria situation in Zambia. These maps can assist to achieve better resource allocation, health management and to target additional interventions to reduce the burden of malaria in Zambia significantly. Repeated surveys will enable the evaluation of the effectiveness of on-going interventions.

Urban agriculture and Anopheles habitats in Dar es Salaam, Tanzania.

A cross-sectional survey of agricultural areas, combined with routinely monitored mosquito larval information, was conducted in urban Dar es Salaam, Tanzania, to investigate how agricultural and geographical features may influence the presence of Anopheles larvae. Data were integrated into a geographical information systems framework, and predictors of the presence of Anopheles larvae in farming areas were assessed using multivariate logistic regression with independent random effects. It was found that more than 5% of the study area (total size 16.8 km2) was used for farming in backyard gardens and larger open spaces. The proportion of habitats containing Anopheles larvae was 1.7 times higher in agricultural areas compared to other areas (95% confidence interval = 1.56-1.92). Significant geographic predictors of the presence of Anopheles larvae in gardens included location in lowland areas, proximity to river, and relatively impermeable soils. Agriculture-related predictors comprised specific seedbed types, mid-sized gardens, irrigation by wells, as well as cultivation of sugar cane or leafy vegetables. Negative predictors included small garden size, irrigation by tap water, rainfed production and cultivation of leguminous crops or fruit trees. Although there was an increased chance of finding Anopheles larvae in agricultural sites, it was found that breeding sites originated by urban agriculture account for less than a fifth of all breeding sites of malaria vectors in Dar es Salaam. It is suggested that strategies comprising an integrated malaria control effort in malaria-endemic African cities include participatory involvement of farmers by planting shade trees near larval habitats.

Spatial distribution of the chromosomal forms of anopheles gambiae in Mali.

BACKGROUND: Maps of the distribution of malaria vectors are useful tools for stratification of malaria risk and for selective vector control strategies. Although the distribution of members of the Anopheles gambiae complex is well documented in Africa, a continuous map of the spatial distribution of the chromosomal forms of An. gambiae s.s. is not yet available at country level to support control efforts. METHODS: Bayesian geostatistical methods were used to produce continuous maps of the spatial distribution of the chromosomal forms of An. gambiae s.s. (Mopti, Bamako, Savanna and their hybrids/recombinants) based on their relative frequencies in relation to climatic and environmental factors in Mali. RESULTS: The maps clearly show that each chromosomal form favours a particular defined eco-climatic zone. The Mopti form prefers the dryer northern Savanna and Sahel and the flooded/irrigated areas of the inner delta of the Niger River. The Savanna form favours the Sudan savanna areas, particularly the South and South-Eastern parts of the country (Kayes and Sikasso regions). The Bamako form has a strong preference for specific environmental conditions and it is confined to the Sudan savanna areas around urban Bamako and the Western part of Sikasso region. The hybrids/recombinants favour the Western part of the country (Kayes region) bordering the Republic of Guinea Conakry. CONCLUSION: The maps provide valuable information for selective vector control in Mali (insecticide resistance management) and may serve as a decision support tool for the basis for future malaria control strategies including genetically manipulated mosquitoes.

Spatial effects of mosquito bednets on child mortality.

BACKGROUND: Insecticide treated nets (ITN) have been proven to be an effective tool in reducing the burden of malaria. Few randomized clinical trials examined the spatial effect of ITNs on child mortality at a high coverage level, hence it is essential to better understand these effects in real-life situation with varying levels of coverage. We analyzed for the first time data from a large follow-up study in an area of high perennial malaria transmission in southern Tanzania to describe the spatial effects of bednets on all-cause child mortality. METHODS: The study was carried out between October 2001 and September 2003 in 25 villages in Kilombero Valley, southern Tanzania. Bayesian geostatistical models were fitted to assess the effect of different bednet density measures on child mortality adjusting for possible confounders. RESULTS: In the multivariate model addressing potential confounding, the only measure significantly associated with child mortality was the bed net density at household level; we failed to observe additional community effect benefit from bed net coverage in the community. CONCLUSION: In this multiyear, 25 village assessment, despite substantial known inadequate insecticide-treatment for bed nets, the density of household bed net ownership was significantly associated with all cause child mortality reduction. The absence of community effect of bednets in our study area might be explained by (1) the small proportion of nets which are treated with insecticide, and (2) the relative homogeneity of coverage with nets in the area. To reduce malaria transmission for both users and non-users it is important to increase the ITNs and long-lasting nets coverage to at least the present untreated nets coverage.

Risk factors for Schistosoma mansoni and hookworm in urban farming communities in western Côte d'Ivoire.

OBJECTIVES: To identify risk factors for Schistosoma mansoni and hookworm infections in urban farming communities, and to investigate small-scale spatial patterns of infection prevalence. METHODS: A cross-sectional survey was carried out in 113 farming households (586 individuals) and 21 non-farming households (130 individuals) from six agricultural zones in the town of Man, western Côte d'Ivoire. Heads of households were interviewed on common agricultural activities, land and water use, education attainment, socioeconomic status and sanitation facilities. Household members provided stool specimens that were processed by the Kato-Katz technique and a formol-ether concentration method and diagnosed for S. mansoni, hookworms and other soil-transmitted helminths and intestinal protozoa. Bayesian statistics were employed for spatial analyses. RESULTS: The prevalences of S. mansoni and hookworm in farming households were 51.4% and 24.7%, respectively. Risk factors for a S. mansoni infection comprised living in close proximity to the Kô River, water contact with irrigation wells and ponds and low education attainment. Living in zones of smallholder irrigated rice plots or large rice perimeters, using water from domestic wells, and low socioeconomic status were risk factors for a hookworm infection. We found significant spatial heterogeneity between agricultural zones, with the highest infection prevalences of S. mansoni and hookworm in the zone where there was a large rice perimeter. CONCLUSIONS: In this urban setting, both S. mansoni and hookworm infections were related to specific agricultural activities. Health education and active participation of urban farmers for the control of schistosomiasis and soil-transmitted helminthiasis is recommended.

Urban farming and malaria risk factors in a medium-sized town in Cote d'Ivoire.

Urbanization occurs at a rapid pace across Africa and Asia and affects people's health and well-being. A typical feature in urban settings of Africa is the maintenance of traditional livelihoods, including agriculture. The purpose of this study was to investigate malaria risk factors in urban farming communities in a medium-sized town in Côte d'Ivoire. Two cross-sectional surveys were carried out among 112 households from six agricultural zones. First, the heads of households were interviewed on agricultural land use, farming practices, water storage, sanitation facilities, and socioeconomic status. Second, a finger prick blood sample was taken from all household members and examined for the occurrence and density of Plasmodia. Geographic coordinates of houses, farming plots, and potential mosquito breeding sites were recorded and integrated into a geographic information system. Predictors of Plasmodium falciparum parasitemia were assessed using non-random and random effects Bayesian regression models. The overall prevalence of P. falciparum was 32.1%. In children < 15 years of age, risk factors for a P. falciparum infection included living in a specific agricultural zone, close proximity to permanent ponds and fish ponds, periodic stays overnight in temporary farm huts, and low socioeconomic status. Our findings indicate that specific crop systems and specific agricultural practices may increase the risk of malaria in urban settings of tropical Africa.

Risk factors and spatial patterns of hookworm infection among schoolchildren in a rural area of western Côte d'Ivoire.

This study is aimed at investigating the risk factors for hookworm infection among schoolchildren in a rural area of western Côte d'Ivoire and predicting and mapping the spatial distribution of infection. We used demographic and socio-economic data from a cross-sectional survey of 6-16-year-old schoolchildren from 56 schools. Infection with hookworm was determined by microscopic examination of stool samples employing the Kato-Katz technique and an ether-concentration method. Environmental data were derived from satellite images and digitised maps. Bayesian variogram models were applied to investigate the variation of hookworm infection in relation to demographic, socio-economic and environmental factors. The overall hookworm infection prevalence, based on the pooled microscopic diagnoses, was 43.3% and ranged from 5.4 to 79.1% in the schools surveyed. Bivariate analyses showed that sex, age, socio-economic status, elevation, rainfall and land cover were significantly associated with the spatial distribution of hookworm infection. The final multivariate spatial model consisted of the covariates age, sex, socio-economic status, elevation and land cover. When assuming non-stationary underlying spatial dependency, the results of the model suggested that spatial correlation depended on the location only marginally. We conclude that, at the current resolution, it seems more reasonable to target interventions based on well-established epidemiologic risk factors, rather than on spatial factors.