Control of schistosomiasis in sub-Saharan Africa: progress made, new opportunities and remaining challenges

Several other journal supplements have documented progress made in the control of schistosomiasis in Egypt, China and Brazil, however, with more than 97% of the schistosome infections now estimated to occur in Africa, the relevance of this special issue in Parasitology cannot be overemphasized. In total, 18 articles are presented, inclusive of a lead-editorial from the WHO highlighting a seminal resolution at the 54th World Health Assembly in 2001 that advocated de-worming. Facilitated by a US$ 30 million grant from the Bill and Melinda Gates Foundation in 2002, the Schistosomiasis Control Initiative subsequently fostered implementation of large-scale schistosomiasis (and soil-transmitted helminthiasis) control programmes in six selected African countries. From 2005, CONTRAST, a European union-funded consortium, was formed to conduct multi-disciplinary research pertaining to optimisation of schistosomiasis control. Progress made in schistosomiasis control across sub-Saharan Africa since the turn of the new millennium is reviewed, shedding light on the latest findings stemming from clinical, epidemiological, molecular and social sciences research, inclusive of public health interventions with monitoring and evaluation activities. New opportunities for integrating the control of schistosomiasis and other so-called neglected tropical diseases are highlighted, but more importantly, several opportune questions that arise from it frame the remaining challenges ahead for an enduring solutio

Differential spatial repositioning of activated genes in Biomphalaria glabrata snails infected with Schistosoma mansoni

Copyright @ 2014 Arican-Goktas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro that Biomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their nuclear location and becoming up-regulated. This also happens in vivo in live intact snails, where early exposure to miracidia also elicits non-random repositioning of genes. We reveal differences in the nuclear repositioning between the response of parasite susceptible snails as compared to resistant snails and with normal or live, attenuated parasites. Interestingly, the stress response gene heat shock protein (Hsp) 70 is only repositioned and then up-regulated in susceptible snails with the normal parasite. This movement and change in gene expression seems to be controlled by the parasite. Other differences in the behaviour of genes support the view that some genes are responding to tissue damage, for example the ferritin genes move and are up-regulated whether the snails are either susceptible or resistant and upon exposure to either normal or attenuated parasite. This is the first time host genome reorganisation has been seen in a parasitic host and only the second time for any pathogen. We believe that the parasite elicits a spatio-epigenetic reorganisation of the host genome to induce favourable gene expression for itself and this might represent a fundamental mechanism present in the human host infected with schistosome cercariae as well as in other host-pathogen relationships.NIH and Sandler Borroughs Wellcome Travel Fellowshi

SchistoDB: a Schistosoma mansoni genome resource

SchistoDB (http://schistoDB.net/) is a genomic database for the parasitic organism Schistosoma mansoni, one of the major causative agents of schistosomiasis worldwide. It currently incorporates sequences and annotation for S. mansoni in a single user-friendly database. Several genomic scale analyses are available as well as ESTs, oligonucleotides, metabolic pathways and drugs. In this article, we describe the data sets and its analyses, how to query the database and tools available in the website

A national survey of the prevalence of schistosomiasis and soil transmitted helminths in Malaŵi

BACKGROUND: Past estimates have put the prevalence of schistosomiasis between 40% and 50% in the Malawi population overall based on studies undertaken ten years or more ago. More recent surveys in known high risk areas find similar levels. However control measures, changing ecology and migration may have led to changes in the prevalence of schistosomiasis in different parts of Malawi. A national schistosomiasis and soil-transmitted helminth (STH) survey was undertaken to measure the distribution, prevalence and intensity of infection in November 2002. METHODS: A school was selected randomly from a random sample of 30 Traditional Authorities stratified by six distinct ecological zones, and 1,664 year 3 pupils (9–10 year olds) were questioned about recent illnesses and "red urine". Samples of urine and faeces were examined for the presence of eggs using the standard Kato-Katz technique for soil-transmitted helminths and intestinal schistosomiasis and urine samples using the filtration technique for Schistosoma haematobium. RESULTS: The prevalence of Schistosoma mansoni is 0.4% (95% CI 0–1.3%), S. haematobium 6.9% (95% CI 1.9 – 11.9%), hookworm 1.3% (95% CI 0.4–2.3%), Ascariasis 0.5% (95% CI 0.1–1.0%) and trichuriasis 0% in year 3 pupils (modal age 10 years of age). Intensity of infection is low for all infections except for 2.5% who have high intensity S. haematobium infection. The "red urine" question is 67% sensitive and 80% specific for positive S. haematobium microscopy. CONCLUSIONS: The reduction in prevalences may be real as a result of recent control measures, or false if historical results were based on surveys of high risk populations. Another explanation is that this survey used an unrepresentative sample of schools. Detailed analysis suggests this is unlikely. Recommendations include the use of a 30% positive threshold for the "red urine" screening question to be used in schoolchildren in high prevalence areas. This survey, based on a national probability sample excluding the northern region lakeside area, finds much lower overall prevalence and intensity of schistosomiasis and STHs than previous estimates based on selected surveys. Disease control featuring chemotherapy may be having a profound effect. The localised nature of the distribution of the infections means that control programmes may work best if undertaken at district level or below. "Red urine" questionnaire surveys may help identify hot spots

Triple Co-Administration of Ivermectin, Albendazole and Praziquantel in Zanzibar: A Safety Study

This paper describes how the use of three drugs which are used separately in mass drug distribution programmes when given together appear safe for use in large populations which have been previously treated with the same drugs separately (Mectizan [ivermectin], albendazole and praziquantel). The target diseases—lymphatic filariasis, soil-transmitted worms and schistosomiasis—were prevalent in Zanzibar up to 2000 but have been largely controlled by mass drug administration. The Ministry of Health and Social Welfare, with the support of WHO, initiated a small scale trial in a population of triple therapy in over 5,000 people initially in two sites, and having found there were no severe adverse events associated with the combined treatment then upscaled to treat the whole of the eligible population of over 700,000. Similarly, there were no severe adverse events. This is the first time the three drugs have been used together at the same time at scale in Africa and provide a basis for expansion of integrated preventive chemotherapy of helminths (worms). The next steps need to be initiated in populations which have heavier worm loads and such interventions need to be subject to close monitoring and ethical review

A Multicentre Randomized Controlled Trial of the Efficacy and Safety of Single-Dose Praziquantel at 40 mg/kg vs. 60 mg/kg for Treating Intestinal Schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil

Control of urinary and intestinal schistosomiasis is based on mass administration of praziquantel at the World Health Organization (WHO) recommended dose of 40 mg/kg, though some countries use 60 mg/kg. This multi-country randomized clinical trial compared the efficacy (cure and egg reduction rates three weeks post-treatment) and safety of these two doses for treating intestinal schistosomiasis in 856 patients in Brazil, Mauritania and Tanzania (Schistosoma mansoni), and The Philippines (S. japonicum). Transmission and infection intensities varied across the sites, but there was no bias or heterogeneity in efficacy outcomes. The two doses are equally effective in curing intestinal schistosomiasis; the higher dose may be less well tolerated, though effects are generally mild and transient. In endemic areas people can be re-infected; one year post-treatment patients on 60 mg/kg had fewer re-infections but this finding is difficult to explain. This study was conducted to respond to the demand for evidence about the dose of praziquantel when deployed in endemic countries. The results, along with those of systematic reviews, support the current WHO recommendation for using praziquantel at 40 mg/kg and should inform policy decisions in countries. The Philippines has already changed from 60 to 40 mg/kg after this study

The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

Predicting the Impact of Long-Term Temperature Changes on the Epidemiology and Control of Schistosomiasis: A Mechanistic Model

, the causative agent of schistosomiasis in humans.The model showed that the impact of temperature on disease prevalence and abundance is not straightforward; the mean infection burden in humans increases up to 30°C, but then crashes at 35°C, primarily due to increased mortalities of the snail intermediate host. In addition, increased temperatures changed the dynamics of disease from stable, endemic infection to unstable, epidemic cycles at 35°C. However, the prevalence of infection was largely unchanged by increasing temperatures. Temperature increases also affected the response of the model to changes in each parameter, indicating certain control strategies may become less effective with local temperature changes. At lower temperatures, the most effective single control strategy is to target the adult parasites through chemotherapy. However, as temperatures increase, targeting the snail intermediate hosts, for example through molluscicide use, becomes more effective. will not respond to increased temperatures in a linear fashion, and the optimal control strategy is likely to change as temperatures change. It is only through a mechanistic approach, incorporating the combined effects of temperature on all stages of the life-cycle, that we can begin to predict the consequences of climate change on the incidence and severity of such diseases