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Background: South Africa accounts for more than a sixth of the global population of people infected with HIV and TB, ranking her highest in HIV/TB co-infection worldwide. Remote areas often bear the greatest burden of morbidity and mortality, yet there are spatial differences within rural settings. Objectives: The primary aim was to investigate HIV/TB mortality determinants and their spatial distribution in the rural Agincourt sub-district for children aged 1-5 years in 2004. Our secondary aim was to model how the associated factors were interrelated as either underlying or proximate factors of child mortality using pathway analysis based on a Mosley-Chen conceptual framework. Methods: We conducted a secondary data analysis based on cross-sectional data collected in 2004 from the Agincourt sub-district in rural northeast South Africa. Child HIV/TB death was the outcome measure derived from physician assessed verbal autopsy. Modelling used multiple logit regression models with and without spatial household random effects. Structural equation models were used in modelling the complex relationships between multiple exposures and the outcome (child HIV/TB mortality) as relayed on a conceptual framework. Results: Fifty-four of 6,692 children aged 1-5 years died of HIV/TB, from a total of 5,084 households. Maternal death had the greatest effect on child HIV/TB mortality (adjusted odds ratio = 4.00; 95% confidence interval = 1.01-15.80). A protective effect was found in households with better socio-economic status and when the child was older. Spatial models disclosed that the areas which experienced the greatest child HIV/TB mortality were those without any health facility. Conclusion: Low socio-economic status and maternal deaths impacted indirectly and directly on child mortality, respectively. These factors are major concerns locally and should be used in formulating interventions to reduce child mortality. Spatial prediction maps can guide policy makers to target inte

Schistosomiasis prevalence data for Nigeria were extracted from peer-reviewed journals and reports, geo-referenced and collated in a nationwide geographical information system database for the generation of point prevalence maps. This exercise revealed that the disease is endemic in 35 of the country's 36 states, including the federal capital territory of Abuja, and found in 462 unique locations out of 833 different survey locations. Schistosoma haematobium, the predominant species in Nigeria, was found in 368 locations (79.8%) covering 31 states, S. mansoni in 78 (16.7%) locations in 22 states and S. intercalatum in 17 (3.7%) locations in two states. S. haematobium and S. mansoni were found to be co-endemic in 22 states, while co-occurrence of all three species was only seen in one state (Rivers). The average prevalence for each species at each survey location varied between 0.5% and 100% for S. haematobium, 0.2% to 87% for S. mansoni and 1% to 10% for S. intercalatum. The estimated prevalence of S. haematobium, based on Bayesian geospatial predictive modelling with a set of bioclimatic variables, ranged from 0.2% to 75% with a mean prevalence of 23% for the country as a whole (95% confidence interval (CI): 22.8-23.1%). The model suggests that the mean temperature, annual precipitation and soil acidity significantly influence the spatial distribution. Prevalence estimates, adjusted for school-aged children in 2010, showed that the prevalence is

The geographical ranges of most species, including many infectious disease agents and their vectors and intermediate hosts, are assumed to be constrained by climatic tolerances, mainly temperature. It has been suggested that global warming will cause an expansion of the areas potentially suitable for infectious disease transmission. However, the transmission of infectious diseases is governed by a myriad of ecological, economic, evolutionary and social factors. Hence, a deeper understanding of the total disease system (pathogens, vectors and hosts) and its drivers is important for predicting responses to climate change. Here, we combine a growing degree day model for Schistosoma mansoni with species distribution models for the intermediate host snail (Biomphalaria spp.) to investigate large-scale environmental determinants of the distribution of the African S. mansoni-Biomphalaria system and potential impacts of climatic changes. Snail species distribution models included several combinations of climatic and habitat-related predictors; the latter divided into "natural" and "human-impacted" habitat variables to measure anthropogenic influence. The predictive performance of the combined snail-parasite model was evaluated against a comprehensive compilation of historical S. mansoni parasitological survey records, and then examined for two climate change scenarios of increasing severity for 2080. Future projections indicate that while the potential S. mansoni transmission area expands, the snail ranges are more likely to contract and/or move into cooler areas in the south and east. Importantly, we also note that even though climate per se matters, the impact of humans on habitat play a crucial role in determining the distribution of the intermediate host snails in Africa. Thus, a future contraction in the geographical range size of the intermediate host snails caused by climatic changes does not necessarily translate into a decrease or zero-sum change in human schistoso

PRINCIPLES: Switzerland is divided into 26 cantons of variable population size and cultural characteristics. Although a federal law to protect against passive smoking and a national tobacco control programme exist, details of tobacco-related policies are canton-specific. This study aimed to project gender-specific tobacco-related cancer mortality in Switzerland at different geographical levels for the periods 2009-2013 and 2014-2018. METHODS: In this analysis, data on Swiss tobacco-related cancer mortality from 1984 until 2008 were used. Bayesian age-period-cohort models were formulated to assess past trends of gender-specific tobacco-related cancer mortality and to project them up to 2018 at cantonal and language region levels. Furthermore, estimates are provided on a national scale by age categories of 50-69 and ≥70 years. RESULTS: Model-based estimates at cantonal level identified regions with low and high tobacco-related cancer mortality rates for the observed and projected periods. Our analysis based on language regions showed the lowest mortality in the German-speaking part. Projections at national level, between younger (age 50-69) and older (age ≥70) males, indicated an ongoing decreasing trend for males but an upward trend for females. The gap in tobacco-related cancer mortality rates between younger and older males seems to be shrinking. In females, a stronger rise was obtained for the younger age group. CONCLUSION: Our findings indicate region-, sex- and age-related differences in tobacco-related cancer mortality in Switzerland and this could be useful for healthcare planning and for evaluating the impact of canton-specific tobacco-related policies and interventions.

Tobacco smoking is a main cause of disease in Switzerland; lung cancer being the most common cancer mortality in men and the second most common in women. Although disease-specific mortality is decreasing in men, it is steadily increasing in women. The four language regions in this country might play a role in this context as they are influenced in different ways by the cultural and social behaviour of neighbouring countries. Bayesian hierarchical spatio-temporal, negative binomial models were fitted on subgroup-specific death rates indirectly standardized by national references to explore age- and gender-specific spatio-temporal patterns of mortality due to lung cancer and other tobacco-related cancers in Switzerland for the time period 1969-2002. Differences influenced by linguistic region and life in rural or urban areas were also accounted for. Male lung cancer mortality was found to be rather homogeneous in space, whereas women were confirmed to be more affected in urban regions. Compared to the German-speaking part, female mortality was higher in the French-speaking part of the country, a result contradicting other reports of similar comparisons between France and Germany. The spatio-temporal patterns of mortality were similar for lung cancer and other tobacco-related cancers. The estimated mortality maps can support the planning in health care services and evaluation of a national tobacco control programme. Better understanding of spatial and temporal variation of cancer of the lung and other tobacco-related cancers may help in allocating resources for more effective screening, diagnosis and therapy. The methodology can be applied to similar studies in other settings.

Schistosomiasis remains one of the most prevalent parasitic diseases in the tropics and subtropics, but current statistics are outdated due to demographic and ecological transformations and ongoing control efforts. Reliable risk estimates are important to plan and evaluate interventions in a spatially explicit and cost-effective manner. We analysed a large ensemble of georeferenced survey data derived from an open-access neglected tropical diseases database to create smooth empirical prevalence maps for Schistosoma mansoni and Schistosoma haematobium for a total of 13 countries of eastern Africa. Bayesian geostatistical models based on climatic and other environmental data were used to account for potential spatial clustering in spatially structured exposures. Geostatistical variable selection was employed to reduce the set of covariates. Alignment factors were implemented to combine surveys on different age-groups and to acquire separate estimates for individuals aged ≤20 years and entire communities. Prevalence estimates were combined with population statistics to obtain country-specific numbers of Schistosoma infections. We estimate that 122 million individuals in eastern Africa are currently infected with either S. mansoni, or S. haematobium, or both species concurrently. Country-specific population-adjusted prevalence estimates range between 12.9% (Uganda) and 34.5% (Mozambique) for S. mansoni and between 11.9% (Djibouti) and 40.9% (Mozambique) for S. haematobium. Our models revealed that infection risk in Burundi, Eritrea, Ethiopia, Kenya, Rwanda, Somalia and Sudan might be considerably higher than previously reported, while in Mozambique and Tanzania, the risk might be lower than current estimates suggest. Our empirical, large-scale, high-resolution infection risk estimates for S. mansoni and S. haematobium in eastern Africa can guide future control interventions and provide a benchmark for subsequent monitoring and evaluation activities.

We assessed morbidity due to Opisthorchis viverrini and Schistosoma mekongi infections in 243 individuals in Lao People's Democratic Republic. Morbidity was associated with O. viverrini infection intensity. Coinfection with S. mekongi resulted in excess risk of liver fibrosis and left liver lobe enlargement. The high public health impact of opisthorchiasis warrants control.

BACKGROUND: Albendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth (STH) infections. We assessed the efficacy of single oral doses of albendazole (400 mg) and mebendazole (500 mg) for the treatment of hookworm infection in school-aged children in Lao PDR. Since Opisthorchis viverrini is co-endemic in our study setting, the effect of the two drugs could also be determined against this liver fluke. METHODOLOGY: We conducted a randomized, open-label, two-arm trial. In total, 200 children infected with hookworm (determined by quadruplicate Kato-Katz thick smears derived from two stool samples) were randomly assigned to albendazole (n=100) and mebendazole (n=100). Cure rate (CR; percentage of children who became egg-negative after treatment), and egg reduction rate (ERR; reduction in the geometric mean fecal egg count at treatment follow-up compared to baseline) at 21-23 days posttreatment were used as primary outcome measures. Adverse events were monitored 3 hours post treatment. PRINCIPAL FINDINGS: Single-dose albendazole and mebendazole resulted in CRs of 36.0% and 17.6% (odds ratio: 0.4; 95% confidence interval: 0.2-0.8; P=0.01), and ERRs of 86.7% and 76.3%, respectively. In children co-infected with O. viverrini, albendazole and mebendazole showed low CRs (33.3% and 24.2%, respectively) and moderate ERRs (82.1% and 78.2%, respectively). CONCLUSIONS/SIGNIFICANCE: Both albendazole and mebendazole showed disappointing CRs against hookworm, but albendazole cured infection and reduced intensity of infection with a higher efficacy than mebendazole. Single-dose administrations showed an effect against O. viverrini, and hence it will be interesting to monitor potential ancillary benefits of a preventive chemotherapy strategy that targets STHs in areas where opisthorchiasis is co-endemic. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ISRCTN29126001.

South Africa is experiencing a major burden of HIV/TB. We used longitudinal data from the Agincourt sub-district in rural northeast South Africa over the years 2000 to 2005. A total of 187 HIV/TB deaths were observed among 16,844 children aged 1-5. years coming from 8,863 households. In this paper we used Bayesian models to assess risk factors for child HIV/TB mortality taking into account the presence of spatial correlation. Bayesian zero inflated spatiotemporal models were able to detect hidden patterns within the data. Our main finding was that maternal orphans experienced a threefold greater risk of HIV/TB death compared to those with living mothers (AHR = 2.93, 95% CI[1.29;6.93]). Risk factor analyses which adjust for person, place and time provide evidence for policy makers that includes a spatial distribution of risk. Child survival is dependent on the mother's survival; hence programs that promote maternal survival are critical.

Targeting of health interventions to poor children at highest risk of mortality are promising approaches for enhancing equity. Methods have emerged to accurately quantify excess risk and identify space-time disparities. This provides useful and detailed information for guiding policy. A spatio-temporal analysis was performed to identify risk factors associated with child (1-4 years) mortality in the Agincourt sub-district, South Africa, to assess temporal changes in child mortality patterns within the study site between 1992 and 2007, and to produce all-cause and cause-specific mortality maps to identify high risk areas. Demographic, maternal, paternal and fertility-related factors, household mortality experience, distance to health care facility and socio-economic status were among the examined risk factors. The analysis was carried out by fitting a Bayesian discrete time Bernoulli survival geostatistical model using Markov chain Monte Carlo simulation. Bayesian kriging was used to produce mortality risk maps. Significant temporal increase in child mortality was observed due to the HIV epidemic. A distinct spatial risk pattern was observed with higher risk areas being concentrated in poorer settlements on the eastern part of the study area, largely inhabited by former Mozambican refugees. The major risk factors for childhood mortality, following multivariate adjustment, were mother's death (especially when due to HIV and tuberculosis), greater number of children under 5 years living in the same household and winter season. This study demonstrates the use of Bayesian geostatistical models for accurately quantifying risk factors and producing maps of child mortality risk in a health and demographic surveillance system. According to the space-time analysis, the southeast and upper central regions of the site appear to have the highest mortality risk. The results inform policies to address health inequalities in the Agincourt sub-district and to improve access to healt

After many years of general neglect, interest has grown and efforts came under way for the mapping, control, surveillance, and eventual elimination of neglected tropical diseases (NTDs). Disease risk estimates are a key feature to target control interventions, and serve as a benchmark for monitoring and evaluation. What is currently missing is a georeferenced global database for NTDs providing open-access to the available survey data that is constantly updated and can be utilized by researchers and disease control managers to support other relevant stakeholders. We describe the steps taken toward the development of such a database that can be employed for spatial disease risk modeling and control of NTDs.

Schistosomiasis is a water-based disease that is believed to affect over 200 million people with an estimated 97% of the infections concentrated in Africa. However, these statistics are largely based on population re-adjusted data originally published by Utroska and colleagues more than 20 years ago. Hence, these estimates are outdated due to large-scale preventive chemotherapy programs, improved sanitation, water resources development and management, among other reasons. For planning, coordination, and evaluation of control activities, it is essential to possess reliable schistosomiasis prevalence maps.

This study has highlighted distinct clusters of all-cause and cause-specific mortality within the Agincourt subdistrict. It is a first step in prioritizing areas for further, more detailed research as well as for future public health follow-on efforts such as targeting of vertical prevention of HIV/TB and antiretroviral rollout in significant child and adult mortality clusters; and assessment and provision of adequate water and sanitation in the child mortality clusters particularly in south-east where diarrheal mortality appears high. Underlying causative factors need to be identified and accurately quantified. Other questions for more detailed research are discussed., Supplement: 1

This study demonstrates the use of Bayesian geostatistical models in assessing risk factors and producing smooth maps of infant mortality risk in a health and socio-demographic surveillance system. Results showed marked geographical differences in mortality risk across a relatively small area. Prevention of vertical transmission of HIV and survival of mothers during the infants' first year in high prevalence villages needs to be urgently addressed, including expanded antenatal testing, prevention of mother-to-child transmission, and improved access to antiretroviral therapy. There is also need to assess and improve the capacity of district hospitals for emergency obstetric and newborn care. Persisting risk factors, including inadequate provision of clean water and sanitation, are yet to be fully addressed.

The rapidly growing field of three-dimensional software modeling of the Earth holds promise for applicationsin the geospatial health sciences. Easy-to-use, intuitive virtual globe technologies such as Google Earth™ enable scien-tists around the world to share their data and research results in a visually attractive and readily understandable fash-ion without the need for highly sophisticated geographical information systems (GIS) or much technical assistance. Thispaper discusses the utility of the rapid and simultaneous visualization of how the agents of parasitic diseases are dis-tributed, as well as that of their vectors and/or intermediate hosts together with other spatially-explicit information.The resulting better understanding of the epidemiology of infectious diseases, and the multidimensional environmentin which they occur, are highlighted. In particular, the value of Google Earth™, and its web-based pendant GoogleMaps™, are reviewed from a public health view point, combining results from literature searches and experiencesgained thus far from a multidisciplinary project aimed at optimizing schistosomiasis control and transmission surveil-lance in sub-Saharan Africa. Although the basic analytical capabilities of virtual globe applications are limited, we con-clude that they have considerable potential in the support and promotion of the geospatial health sciences as a user-friendly, straightforward GIS tool for the improvement of data collation, visualization and exploration. The potentialof these systems for data sharing and broad dissemination of scientific research and results is emphasized.