Impaired immune responses to herpesviruses and microbial ligands in patients with MonoMAC.

MonoMAC is a complex primary immunodeficiency caused by mutations in the myeloid transcription factor GATA2, characterized by multilineage cytopenia with malignant complications and severe infections, including mycobacteria and herpesviruses. We describe the clinical presentation, genetics and antiviral inflammatory responses in a small case series. Two patients presented in childhood with mycobacterial infection and were diagnosed with MonoMAC germline GATA2 variants; their healthy fathers with the same mutations were also studied. Three patients were elderly individuals with acquired GATA2 mutations and malignant haematological conditions. Overall, this study demonstrates the heterogeneous clinical presentation and variation in immunodeficiency caused by GATA2 mutations.

Environmental DNA for improved detection and environmental surveillance of schistosomiasis.

Schistosomiasis is a water-based, infectious disease with high morbidity and significant economic burdens affecting >250 million people globally. Disease control has, with notable success, for decades focused on drug treatment of infected human populations, but a recent paradigm shift now entails moving from control to elimination. To achieve this ambitious goal, more sensitive diagnostic tools are needed to monitor progress toward transmission interruption in the environment, especially in low-intensity infection areas. We report on the development of an environmental DNA (eDNA)-based tool to efficiently detect DNA traces of the parasite Schistosoma mansoni directly in the aquatic environment, where the nonhuman part of the parasite life cycle occurs. This is a report of the successful detection of S. mansoni in freshwater samples by using aquatic eDNA. True eDNA was detected in as few as 10 cercariae per liter of water in laboratory experiments. The field applicability of the method was tested at known transmission sites in Kenya, where comparison of schistosome detection by conventional snail surveys (snail collection and cercariae shedding) with eDNA (water samples) showed 71% agreement between the methods. The eDNA method furthermore detected schistosome presence at two additional sites where snail shedding failed, demonstrating a higher sensitivity of eDNA sampling. We conclude that eDNA provides a promising tool to substantially improve the environmental surveillance of S. mansoni Given the proper method and guideline development, eDNA could become an essential future component of the schistosomiasis control tool box needed to achieve the goal of elimination.

Comparison of the spatial patterns of schistosomiasis in Zimbabwe at two points in time, spaced twenty-nine years apart: is climate variability of importance?

Temperature, precipitation and humidity are known to be important factors for the development of schistosome parasites as well as their intermediate snail hosts. Climate therefore plays an important role in determining the geographical distribution of schistosomiasis and it is expected that climate change will alter distribution and transmission patterns. Reliable predictions of distribution changes and likely transmission scenarios are key to efficient schistosomiasis intervention-planning. However, it is often difficult to assess the direction and magnitude of the impact on schistosomiasis induced by climate change, as well as the temporal transferability and predictive accuracy of the models, as prevalence data is often only available from one point in time. We evaluated potential climate-induced changes on the geographical distribution of schistosomiasis in Zimbabwe using prevalence data from two points in time, 29 years apart; to our knowledge, this is the first study investigating this over such a long time period. We applied historical weather data and matched prevalence data of two schistosome species (Schistosoma haematobium and S. mansoni). For each time period studied, a Bayesian geostatistical model was fitted to a range of climatic, environmental and other potential risk factors to identify significant predictors that could help us to obtain spatially explicit schistosomiasis risk estimates for Zimbabwe. The observed general downward trend in schistosomiasis prevalence for Zimbabwe from 1981 and the period preceding a survey and control campaign in 2010 parallels a shift towards a drier and warmer climate. However, a statistically significant relationship between climate change and the change in prevalence could not be established.

Ecological Drivers of Mansonella perstans Infection in Uganda and Patterns of Co-endemicity with Lymphatic Filariasis and Malaria.

BACKGROUND: Mansonella perstans is a widespread, but relatively unknown human filarial parasite transmitted by Culicoides biting midges. Although it is found in many parts of sub-Saharan Africa, only few studies have been carried out to deepen the understanding of its ecology, epidemiology, and health consequences. Hence, knowledge about ecological drivers of the vector and parasite distribution, integral to develop spatially explicit models for disease prevention, control, and elimination strategies, is limited. METHODOLOGY: We analyzed data from a comprehensive nationwide survey of M. perstans infection conducted in 76 schools across Uganda in 2000-2003, to identify environmental drivers. A suite of Bayesian geostatistical regression models was fitted, and the best fitting model based on the deviance information criterion was utilized to predict M. perstans infection risk for all of Uganda. Additionally, we investigated co-infection rates and co-distribution with Wuchereria bancrofti and Plasmodium spp. infections observed at the same survey by mapping geographically overlapping areas. PRINCIPAL FINDINGS: Several bioclimatic factors were significantly associated with M. perstans infection levels. A spatial Bayesian regression model showed the best fit, with diurnal temperature range, normalized difference vegetation index, and cattle densities identified as significant covariates. This model was employed to predict M. perstans infection risk at non-sampled locations. The level of co-infection with W. bancrofti was low (0.3%), due to limited geographic overlap. However, where the two infections did overlap geographically, a positive association was found. CONCLUSIONS/SIGNIFICANCE: This study presents the first geostatistical risk map for M. perstans in Uganda. We confirmed a widespread distribution of M. perstans, and identified important potential drivers of risk. The results provide new insight about the ecologic preferences of this otherwise poorly known filarial parasite and its Culicoides vector species in Uganda, which might be relevant for other settings in sub-Saharan Africa.

Multidisciplinary Management of Mastocytosis: Nordic Expert Group Consensus.

Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.

Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology.

Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma.

Modelling climate change impact on the spatial distribution of fresh water snails hosting trematodes in Zimbabwe.

BACKGROUND: Freshwater snails are intermediate hosts for a number of trematodes of which some are of medical and veterinary importance. The trematodes rely on specific species of snails to complete their life cycle; hence the ecology of the snails is a key element in transmission of the parasites. More than 200 million people are infected with schistosomes of which 95% live in sub-Saharan Africa and many more are living in areas where transmission is on-going. Human infection with the Fasciola parasite, usually considered more of veterinary concern, has recently been recognised as a human health problem. Many countries have implemented health programmes to reduce morbidity and prevalence of schistosomiasis, and control programmes to mitigate food-borne fascioliasis. As these programmes are resource demanding, baseline information on disease prevalence and distribution becomes of great importance. Such information can be made available and put into practice through maps depicting spatial distribution of the intermediate snail hosts. METHODS: A biology driven model for the freshwater snails Bulinus globosus, Biomphalaria pfeifferi and Lymnaea natalensis was used to make predictions of snail habitat suitability by including potential underlying environmental and climatic drivers. The snail observation data originated from a nationwide survey in Zimbabwe and the prediction model was parameterised with a high resolution Regional Climate Model. Georeferenced prevalence data on urinary and intestinal schistosomiasis and fascioliasis was used to calibrate the snail habitat suitability predictions to produce binary maps of snail presence and absence. RESULTS: Predicted snail habitat suitability across Zimbabwe, as well as the spatial distribution of snails, is reported for three time slices representative for present (1980-1999) and future climate (2046-2065 and 2080-2099). CONCLUSIONS: It is shown from the current study that snail habitat suitability is highly variable in Zimbabwe, with distinct high- and low- suitability areas and that temperature may be the main driving factor. It is concluded that future climate change in Zimbabwe may cause a reduced spatial distribution of suitable habitat of host snails with a probable exception of Bi. pfeifferi, the intermediate host for intestinal schistosomiasis that may increase around 2055 before declining towards 2100.

Modelling spatial distribution of snails transmitting parasitic worms with importance to human and animal health and analysis of distributional changes in relation to climate.

The environment, the on-going global climate change and the ecology of animal species determine the localisation of habitats and the geographical distribution of the various species in nature. The aim of this study was to explore the effects of such changes on snail species not only of interest to naturalists but also of importance to human and animal health. The spatial distribution of freshwater snail intermediate hosts involved in the transmission of schistosomiasis, fascioliasis and paramphistomiasis (i.e. Bulinus globosus, Biomphalaria pfeifferi and Lymnaea natalensis) were modelled by the use of a maximum entropy algorithm (Maxent). Two snail observation datasets from Zimbabwe, from 1988 and 2012, were compared in terms of geospatial distribution and potential distributional change over this 24-year period investigated. Climate data, from the two years were identified and used in a species distribution modelling framework to produce maps of predicted suitable snail habitats. Having both climate- and snail observation data spaced 24 years in time represent a unique opportunity to evaluate biological response of snails to changes in climate variables. The study shows that snail habitat suitability is highly variable in Zimbabwe with foci mainly in the central Highveld but also in areas to the South and West. It is further demonstrated that the spatial distribution of suitable habitats changes with variation in the climatic conditions, and that this parallels that of the predicted climate change.

Schistosomiasis research in Africa: how the CONTRAST alliance made it happen.

In May 2012, the World Health Assembly passed resolution WHA 65.21, calling upon member states to intensify schistosomiasis control and, wherever possible, to attempt transmission interruption and initiate interventions towards local elimination. It is now clear that CONTRAST--a multidisciplinary alliance to optimize schistosomiasis control and transmission surveillance in sub-Saharan Africa--was ahead of the game. Indeed, launched in October 2006, this 4-year project funded by the European Commission made important contributions for sustainable schistosomiasis control in the selected African countries through innovation, validation and application of new tools and locally adapted intervention strategies complementary to preventive chemotherapy. Moreover, CONTRAST articulated a research agenda for schistosomiasis elimination, framed by 10 key questions. Here, we provide a rationale for CONTRAST and discuss its overarching goal, the interrelated objectives, establishment and running of a research node network across Africa, partnership configuration and modus operandi of the project. A collection of 25 articles is presented that are grouped into five main themes: molecular, biological, spatial, social and cross-cutting issues pertaining to the epidemiology and control of schistosomiasis. We summarize key achievements made by CONTRAST, many of which are featured in this special issue of Acta Tropica. Together with an independent view put forth by an eminent schistosomiasis researcher, the current piece provides an umbrella for the 25-article collection, including current gaps and remaining research needs. Finally, post-CONTRAST initiatives are discussed and a speculative viewpoint is given on how schistosomiasis control/elimination will have evolved over the next several years.

Mapping and prediction of schistosomiasis in Nigeria using compiled survey data and Bayesian geospatial modelling.

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 <10% in most states with a few reaching as high as 50%. It was estimated that 11.3 million children require praziquantel annually (95% CI: 10.3-12.2 million).

Collection, verification, sharing and dissemination of data: the CONTRAST experience.

The scientific community is charged with growing demands regarding the management of project data and outputs and the dissemination of key results to various stakeholders. We discuss experiences and lessons from CONTRAST, a multidisciplinary alliance that had been funded by the European Commission over a 4-year period, in order to optimize schistosomiasis control and transmission surveillance in sub-Saharan Africa. From the start, project partners from Europe and Africa set out an ambitious goal: to sample data following standard protocols at all field sites and then sharing the data in a way that would enable all project partners to have access through a password-protected Internet-based data portal. This required anonymous agreement on several common standardized sample forms, ranging from the mundane but important issue of using the same units of measurement to more complex challenges, for instance agreeing on the same protocols for double-treatment of praziquantel in different settings. With the experiences gained by the CONTRAST project, this paper discusses issues of data management and sharing in research projects in the light of the current donor demand, and offers advice and specific suggestions for similar interdisciplinary research projects.

Compatibility of Ugandan Schistosoma mansoni isolates with Biomphalaria snail species from Lake Albert and Lake Victoria.

In order to investigate the capacity of being intermediate host for Schistosoma mansoni, the Ugandan F1 generation of Biomphalaria snail species that were laboratory-bred from parent populations originally collected from either Lake Victoria or Lake Albert was challenged with sympatric and non-sympatric S. mansoni isolates. After a prepatent period of 20 days, a daily 10-hourly snail shedding for cercariae was done to determine the infection rate, cercarial production per hour and survival period of infected snails. The study suggests that when parasite strains from a different geographical origin is used for infection, survival of infected snails increase, leading to an increased transmission potential. Although earlier literature had indicated that the Lake Victoria Biomphalaria sudanica is refractory to S. mansoni, we showed that all Ugandan Biomphalaria spp., including B. sudanica from all locations, were highly susceptible to the S. mansoni isolates. Thus if B. choanomphala, which is an efficient intermediate host in Lake Victoria, is given an opportunity to occupy Lake Albert, it will most likely be compatible with the Albertine S. mansoni parasites. Equally, if B. stanleyi, currently restricted to Lake Albert invades Lake Victoria, it is likely to act as an efficient intermediate host. Future work should concentrate on intraspecific population-level differences in compatibility.

Bulinus globosus (Planorbidae; Gastropoda) populations in the Lake Victoria basin and coastal Kenya show extreme nuclear genetic differentiation.

Bulinus globosus, a key intermediate host for Schistosoma haematobium that causes urinary schistosomiasis, is a hermaphroditic freshwater Planorbid snail species that inhabits patchy and transient water bodies prone to large seasonal variations in water availability. Although capable of self-fertilizing, this species has been reported to be preferentially out crossing. In this study, we characterized the population genetic structure of 19 B. globosus populations sampled across the Lake Victoria basin and coastal Kenya using four polymorphic microsatellite loci. Population genetic structure was characterized and quantified using FST statistics and Bayesian clustering algorithms. The four loci used in this study contained sufficient statistical power to detect low levels of population genetic differentiation and were highly polymorphic with the number of alleles per locus across populations ranging from 16 to 22. Average observed and expected heterozygosities across loci in each population ranged from 0.13 to 0.69 and from 0.39 to 0.79, respectively. Twenty-five of the seventy-six possible population-locus comparisons significantly deviated from Hardy-Weinberg equilibrium proportions after Bonferroni corrections, mostly due to the deficiency of heterozygotes. Significant genetic differentiation was observed between populations and Bayesian inferences identified 15 genetic clusters. The excess homozygosity, significant inbreeding and population genetic differentiation observed in B. globosus populations are likely to be due to the habitat patchiness, mating system and the proneness to cyclic extinction and recolonization in transient habitats.

Spatially explicit Schistosoma infection risk in eastern Africa using Bayesian geostatistical modelling.

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.

Large-scale determinants of intestinal schistosomiasis and intermediate host snail distribution across Africa: does climate matter?

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 schistosomiasis prevalence.

Urokinase-type plasminogen activator-like proteases in teleosts lack genuine receptor-binding epidermal growth factor-like domains.

Plasminogen activation catalyzed by urokinase-type plasminogen activator (uPA) plays an important role in normal and pathological tissue remodeling processes. Since its discovery in the mid-1980s, the cell membrane-anchored urokinase-type plasminogen activator receptor (uPAR) has been believed to be central to the functions of uPA, as uPA-catalyzed plasminogen activation activity appeared to be confined to cell surfaces through the binding of uPA to uPAR. However, a functional uPAR has so far only been identified in mammals. We have now cloned, recombinantly produced, and characterized two zebrafish proteases, zfuPA-a and zfuPA-b, which by several criteria are the fish orthologs of mammalian uPA. Thus, both proteases catalyze the activation of fish plasminogen efficiently and both proteases are inhibited rapidly by plasminogen activator inhibitor-1 (PAI-1). But zfuPA-a differs from mammalian uPA by lacking the exon encoding the uPAR-binding epidermal growth factor-like domain; zfuPA-b differs from mammalian uPA by lacking two cysteines of the epidermal growth factor-like domain and a uPAR-binding sequence comparable with that found in mammalian uPA. Accordingly, no zfuPA-b binding activity could be found in fish white blood cells or fish cell lines. We therefore propose that the current consensus of uPA-catalyzed plasminogen activation taking place on cell surfaces, derived from observations with mammals, is too narrow. Fish uPAs appear incapable of receptor binding in the manner known from mammals and uPA-catalyzed plasminogen activation in fish may occur mainly in solution. Studies with nonmammalian vertebrate species are needed to obtain a comprehensive understanding of the mechanism of plasminogen activation.

Toward an open-access global database for mapping, control, and surveillance of neglected tropical diseases.

BACKGROUND: 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. METHODOLOGY: With an emphasis on schistosomiasis in Africa, we systematically searched the literature (peer-reviewed journals and 'grey literature'), contacted Ministries of Health and research institutions in schistosomiasis-endemic countries for location-specific prevalence data and survey details (e.g., study population, year of survey and diagnostic techniques). The data were extracted, georeferenced, and stored in a MySQL database with a web interface allowing free database access and data management. PRINCIPAL FINDINGS: At the beginning of 2011, our database contained more than 12,000 georeferenced schistosomiasis survey locations from 35 African countries available under http://www.gntd.org. Currently, the database is expanded to a global repository, including a host of other NTDs, e.g. soil-transmitted helminthiasis and leishmaniasis. CONCLUSIONS: An open-access, spatially explicit NTD database offers unique opportunities for disease risk modeling, targeting control interventions, disease monitoring, and surveillance. Moreover, it allows for detailed geostatistical analyses of disease distribution in space and time. With an initial focus on schistosomiasis in Africa, we demonstrate the proof-of-concept that the establishment and running of a global NTD database is feasible and should be expanded without delay.

Bayesian geostatistical modelling of malaria and lymphatic filariasis infections in Uganda: predictors of risk and geographical patterns of co-endemicity.

BACKGROUND: In Uganda, malaria and lymphatic filariasis (causative agent Wuchereria bancrofti) are transmitted by the same vector species of Anopheles mosquitoes, and thus are likely to share common environmental risk factors and overlap in geographical space. In a comprehensive nationwide survey in 2000-2003 the geographical distribution of W. bancrofti was assessed by screening school-aged children for circulating filarial antigens (CFA). Concurrently, blood smears were examined for malaria parasites. In this study, the resultant malariological data are analysed for the first time and the CFA data re-analysed in order to identify risk factors, produce age-stratified prevalence maps for each infection, and to define the geographical patterns of Plasmodium sp. and W. bancrofti co-endemicity. METHODS: Logistic regression models were fitted separately for Plasmodium sp. and W. bancrofti within a Bayesian framework. Models contained covariates representing individual-level demographic effects, school-level environmental effects and location-based random effects. Several models were fitted assuming different random effects to allow for spatial structuring and to capture potential non-linearity in the malaria- and filariasis-environment relation. Model-based risk predictions at unobserved locations were obtained via Bayesian predictive distributions for the best fitting models. Maps of predicted hyper-endemic malaria and filariasis were furthermore overlaid in order to define areas of co-endemicity. RESULTS: Plasmodium sp. parasitaemia was found to be highly endemic in most of Uganda, with an overall population adjusted parasitaemia risk of 47.2% in the highest risk age-sex group (boys 5-9 years). High W. bancrofti prevalence was predicted for a much more confined area in northern Uganda, with an overall population adjusted infection risk of 7.2% in the highest risk age-group (14-19 year olds). Observed overall prevalence of individual co-infection was 1.1%, and the two infections overlap geographically with an estimated number of 212,975 children aged 5 - 9 years living in hyper-co-endemic transmission areas. CONCLUSIONS: The empirical map of malaria parasitaemia risk for Uganda presented in this paper is the first based on coherent, national survey data, and can serve as a baseline to guide and evaluate the continuous implementation of control activities. Furthermore, geographical areas of overlap with hyper-endemic W. bancrofti transmission have been identified to help provide a better informed platform for integrated control.

Geostatistical model-based estimates of Schistosomiasis prevalence among individuals aged ≤ 20 years in West Africa.

BACKGROUND: 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. METHODOLOGY: We analyzed survey data compiled on a newly established open-access global neglected tropical diseases database (i) to create smooth empirical prevalence maps for Schistosoma mansoni and S. haematobium for individuals aged ≤ 20 years in West Africa, including Cameroon, and (ii) to derive country-specific prevalence estimates. We used Bayesian geostatistical models based on environmental predictors to take into account potential clustering due to common spatially structured exposures. Prediction at unobserved locations was facilitated by joint kriging. PRINCIPAL FINDINGS: Our models revealed that 50.8 million individuals aged ≤ 20 years in West Africa are infected with either S. mansoni, or S. haematobium, or both species concurrently. The country prevalence estimates ranged between 0.5% (The Gambia) and 37.1% (Liberia) for S. mansoni, and between 17.6% (The Gambia) and 51.6% (Sierra Leone) for S. haematobium. We observed that the combined prevalence for both schistosome species is two-fold lower in Gambia than previously reported, while we found an almost two-fold higher estimate for Liberia (58.3%) than reported before (30.0%). Our predictions are likely to overestimate overall country prevalence, since modeling was based on children and adolescents up to the age of 20 years who are at highest risk of infection. CONCLUSION/SIGNIFICANCE: We present the first empirical estimates for S. mansoni and S. haematobium prevalence at high spatial resolution throughout West Africa. Our prediction maps allow prioritizing of interventions in a spatially explicit manner, and will be useful for monitoring and evaluation of schistosomiasis control programs.

Geospatial health: the first five years.

Geospatial Health is an international, peer-reviewed scientific journal produced by the Global Network for Geospatial Health (GnosisGIS). This network was founded in 2000 and the inaugural issue of its official journal was published in November 2006 with the aim to cover all aspects of geographical information system (GIS) applications, remote sensing and other spatial analytic tools focusing on human and veterinary health. The University of Naples Federico II is the publisher, producing two issues per year, both as hard copy and an open-access online version. The journal is referenced in major databases, including CABI, ISI Web of Knowledge and PubMed. In 2008, it was assigned its first impact factor (1.47), which has now reached 1.71. Geospatial Health is managed by an editor-in-chief and two associate editors, supported by five regional editors and a 23-member strong editorial board. This overview takes stock of the first five years of publishing: 133 contributions have been published so far, primarily original research (79.7%), followed by reviews (7.5%), announcements (6.0%), editorials and meeting reports (3.0% each) and a preface in the first issue. A content analysis of all the original research articles and reviews reveals that three quarters of the publications focus on human health with the remainder dealing with veterinary health. Two thirds of the papers come from Africa, Asia and Europe with similar numbers of contributions from each continent. Studies of more than 35 different diseases, injuries and risk factors have been presented. Malaria and schistosomiasis were identified as the two most important diseases (11.2% each). Almost half the contributions were based on GIS, one third on spatial analysis, often using advanced Bayesian geostatistics (13.8%), and one quarter on remote sensing. The 120 original research articles, reviews and editorials were produced by 505 authors based at institutions and universities in 52 countries. Importantly, a considerable proportion of the authors come from countries with a low or medium human development index (29.3%). In view of the increasing number of submissions, we are considering to publish more than two issues per year in the future. Finally, our vision is to open-up a new section predominantly based on visual presentations, including brief video clips, as discussed in a symposium at the 60th annual meeting of the American Society of Tropical Medicine and Hygiene in December 2011.