The control of schistosomiasis and soil-transmitted helminths in East Africa

As a result of support from the Bill and Melinda Gates Foundation, schistosomiasis and intestinal or soil-transmitted helminth infections have been the subject of national control programmes in three Eastern and Southern African countries: Uganda, the United Republic of Tanzania and Zambia. Here, we review the significant progress made in their control efforts and highlight the different approaches being adopted to ensure programme effectiveness and sustainability. Although a positive start has been made to reduce morbidity resulting from schistosomiasis and soil-transmitted helminth infections in these countries, it is imperative that support is identified to sustain the programmes until these infections are no longer a public health problem and children can therefore be given a healthy start to life.     

Control of schistosomiasis--a global picture

The control of schistosomiasis has been a challenging task for most endemic countries. Thus, despite the concerted efforts to date, schistosomiasis remains a major public health concern, second only to malaria in the tropics and subtropics. In this review, Lorenzo Savioli and colleagues highlight changes in schistosomiasis prevalence and distribution over the past decades, discuss the success and limitations of the various control strategies, and present possible control initiatives for the future.     

Schistosomiasis in infants and pre-school-aged children in sub-Saharan Africa: implication for control

Until recently, the epidemiology and control of schistosomiasis in sub-Saharan Africa have focused primarily on infections in school-aged children and to a lesser extent on adults. Now there is growing evidence and reports of infection in infants and pre-school-aged children (≤ 6 years old) in Ghana, Kenya, Mali, Niger, Nigeria and Uganda, with reported prevalence from 14% to 86%. In this review, we provide available information on the epidemiology, transmission and control of schistosomiasis in this age group, generally not considered or included in national schistosomiasis control programmes that are being implemented in several sub-Saharan African countries. Contrary to previous assumptions, we show that schistosomiasis infection starts from early childhood in many endemic communities and factors associated with exposure of infants and pre-school-aged children to infection are yet to be determined. The development of morbidity early in childhood may contribute to long-term clinical impact and severity of schistosomiasis before they receive treatment. Consistently, these issues are overlooked in most schistosomiasis control programmes. It is, therefore, necessary to review current policy of schistosomiasis control programmes in sub-Saharan Africa to consider the treatment of infant and pre-school-aged children and the health education to mothers.     

Elimination of schistosomiasis in China: Current status and future prospects

Elimination of schistosomiasis as a public health problem among all disease-endemic countries in 2030 is an ambitious goal. Recent achievements resulting from mass drug administration (MDA) with praziquantel is promising but may need to be complemented with also other means. Schistosomiasis was highly prevalent in China before the initiation of the national schistosomiasis control program in the mid-1950s, and, at that time, the country bore the world’s highest burden of schistosomiasis. The concerted control efforts, upheld without interruption for more than a half century, have resulted in elimination of the disease as a public health problem in China as of 2015. Here, we describe the current status of schistosomiasis in China, analyze the potential challenges affecting schistosomiasis elimination, and propose the future research needs and priorities for the country, aiming to provide more universal insights into the structures needed for a global schistosomiasis elimination encompassing also other endemic regions.     

Multimedia materials for education, training, and advocacy in international health: experiences with the Schistosomiasis Control Initiative CD-ROM

We describe an innovative use of multimedia materials to support training and advocacy within a schistosomiasis control programme. The Schistosomiasis Control Initiative (SCI) at Imperial College London works with selected sub-Saharan African countries to develop schistosomiasis control programmes. Two elements of the SCI programme were supported by multimedia materials developed at the Wellcome Trust in collaboration with the SCI: (1) training of programme managers, district health officers, and those delivering practical elements of the programme; and (2) advocacy targeted at decision-makers and donors. Evaluation of the materials revealed high reported ratings for both user satisfaction and impact from use of the product. From this experience we draw out several general messages about development of multimedia materials and how these will play a growing future role in promoting training within international health.     

The economics of schistosomiasis chemotherapy

The optimal choice o f chemotherapy regime arises in the design o f every schistosomiasis control programme. This choice is o f particular contemporary interest for two reasons. At one extreme the development of effective single-dose oral drugs such as praziquantel and oxamniquine makes mass chemotherapy a practical option. At the other extreme there has been a revival o f advocacy for some form o f selective treatment. But all developing countries that contemplate schistosomiasis control face severe budget constraints, requiring careful analysis o f the economics o f chemotherapy. In this article, Nick Prescott presents a generalized framework For resource allocation in schistosomiasis chemotherapy, demonstrating that the optimal choice o f chemotherapy regime depends critically on the level of budget constraint, the unit costs o f screening and treatment, and rates o f compliance with screening and chemotherapy-all factors which are usually neglected in the choice o f control strategy.     

A systematic literature review of schistosomiasis in urban and peri-urban settings

BackgroundSchistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and belongs to the neglected tropical diseases. The disease has been reported in 78 countries, with around 290.8 million people in need of treatment in 2018. Schistosomiasis is predominantly considered a rural disease with a subsequent focus of research and control activities in rural settings. Over the past decades, occurrence and even expansion of schistosomiasis foci in peri-urban and urban settings have increasingly been observed. Rural–urban migration in low- and middle-income countries and subsequent rapid and unplanned urbanization are thought to explain these observations. Fifty-five percent (55%) of the world population is already estimated to live in urban areas, with a projected increase to 68% by 2050. In light of rapid urbanization and the efforts to control morbidity and ultimately achieve elimination of schistosomiasis, it is important to deepen our understanding of the occurrence, prevalence, and transmission of schistosomiasis in urban and peri-urban settings. A systematic literature review looking at urban and peri-urban schistosomiasis was therefore carried out as a first step to address the research and mapping gap.MethodologyFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic computer-aided literature review was carried out using PubMed, ScienceDirect, and the World Health Organization Database in November 2019, which was updated in March 2020. Only papers for which at least the abstract was available in English were used. Relevant publications were screened, duplicates were removed, guidelines for eligibility were applied, and eligible studies were reviewed. Studies looking at human Schistosoma infections, prevalence, and intensity of infection in urban and peri-urban settings were included as well as those focusing on the intermediate host snails.Principal findingsA total of 248 publications met the inclusion criteria. The selected studies confirm that schistosomiasis is prevalent in peri-urban and urban areas in the countries assessed. Earlier studies report higher prevalence levels in urban settings compared to data extracted from more recent publications, yet the challenge of migration, rapid uncontrolled urbanization, and resulting poor living conditions highlight the potential for continuous or even newly established transmission to take place.ConclusionsThe review indicates that schistosomiasis has long existed in urban and peri-urban areas and remains a public health problem. There is, however, a challenge of comparability of settings due to the lack of a clear definition of what constitutes urban and peri-urban. There is a pressing need for improved monitoring of schistosomiasis in urban communities and consideration of treatment strategies.     

Large-scale preventive chemotherapy for the control of helminth infection in Western Pacific countries: six years later

In 2001, Urbani and Palmer published a review of the epidemiological situation of helminthiases in the countries of the Western Pacific Region of the World Health Organization indicating the control needs in the region. Six years after this inspiring article, large-scale preventive chemotherapy for the control of helminthiasis has scaled up dramatically in the region. This paper analyzes the most recent published and unpublished country information on large-scale preventive chemotherapy and summarizes the progress made since 2000. Almost 39 million treatments were provided in 2006 in the region for the control of helminthiasis: nearly 14 million for the control of lymphatic filariasis, more than 22 million for the control of soil-transmitted helminthiasis, and over 2 million for the control of schistosomiasis. In general, control of these helminthiases is progressing well in the Mekong countries and Pacific Islands. In China, despite harboring the majority of the helminth infections of the region, the control activities have not reached the level of coverage of countries with much more limited financial resources. The control of food-borne trematodes is still limited, but pilot activities have been initiated in China, Lao People's Democratic Republic, and Vietnam.     

Determining Treatment Needs at Different Spatial Scales Using Geostatistical Model-Based Risk Estimates of Schistosomiasis

Background

After many years of neglect, schistosomiasis control is going to scale. The strategy of choice is preventive chemotherapy, that is the repeated large-scale administration of praziquantel (a safe and highly efficacious drug) to at-risk populations. The frequency of praziquantel administration is based on endemicity, which usually is defined by prevalence data summarized at an arbitrarily chosen administrative level.

Methodology

For an ensemble of 29 West and East African countries, we determined the annualized praziquantel treatment needs for the school-aged population, adhering to World Health Organization guidelines. Different administrative levels of prevalence aggregation were considered; country, province, district, and pixel level. Previously published results on spatially explicit schistosomiasis risk in the selected countries were employed to classify each area into distinct endemicity classes that govern the frequency of praziquantel administration.

Principal Findings

Estimates of infection prevalence adjusted for the school-aged population in 2010 revealed that most countries are classified as moderately endemic for schistosomiasis (prevalence 10–50%), while four countries (i.e., Ghana, Liberia, Mozambique, and Sierra Leone) are highly endemic (>50%). Overall, 72.7 million annualized praziquantel treatments (50% confidence interval (CI): 68.8–100.7 million) are required for the school-aged population if country-level schistosomiasis prevalence estimates are considered, and 81.5 million treatments (50% CI: 67.3–107.5 million) if estimation is based on a more refined spatial scale at the provincial level.

Conclusions/Significance

Praziquantel treatment needs may be over- or underestimated depending on the level of spatial aggregation. The distribution of schistosomiasis in Ethiopia, Liberia, Mauritania, Uganda, and Zambia is rather uniform, and hence country-level risk estimates are sufficient to calculate treatment needs. On the other hand, countries like Burkina Faso, Mali, Mozambique, Sudan, and Tanzania show large spatial heterogeneity in schistosomiasis risk, which should be taken into account for calculating treatment requirements.     

Developing vaccines to combat hookworm infection and intestinal schistosomiasis

Hookworm infection and schistosomiasis rank among the most important health problems in developing countries. Both cause anaemia and malnutrition, and schistosomiasis also results in substantial intestinal, liver and genitourinary pathology. In sub-Saharan Africa and Brazil, co-infections with the hookworm, Necator americanus, and the intestinal schistosome, Schistosoma mansoni, are common. The development of vaccines for these infections could substantially reduce the global disability associated with these helminthiases. New genomic, proteomic, immunological and X-ray crystallographic data have led to the discovery of several promising candidate vaccine antigens. Here, we describe recent progress in this field and the rationale for vaccine development.     

Protein tyrosine kinases as new potential targets against human schistosomiasis

In spite of the numerous efforts made to control their transmission, parasite schistosomes still represent a serious public health concern and a major economic problem in many developing countries. Praziquantel (PZQ) is the drug of choice for the treatment of schistosomiasis and the only one that is available for mass chemotherapy. However, its widespread use and its inefficacy on juvenile parasites raise fears that schistosomes will develop drug resistance, and make the development of alternative drugs highly desirable. Protein tyrosine kinases (PTKs) are key molecules that control cell differentiation and proliferation and they already represent important targets for molecular cancer therapy. The recent characterization in Schistosoma mansoni of several cytosolic and receptor PTKs, with properties similar but also divergent from their vertebrate counterparts, opens new perspectives for the development of novel strategies in chemotherapy of schistosomiasis, which could be based on the use of parasite-specific tyrosine phosphorylation inhibitors.     

How to (or Not to) Integrate Vertical Programmes for the Control of Major Neglected Tropical Diseases in Sub-Saharan Africa

Combining the delivery of multiple health interventions has the potential to minimize costs and expand intervention coverage. Integration of mass drug administration is therefore being encouraged for delivery of preventive chemotherapy (PCT) to control onchocerciasis, lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma in sub-Saharan Africa, as there is considerable geographical overlap of these neglected tropical diseases (NTDs). With only a handful of countries having embarked on integrated NTD control, experience on how to develop and implement an efficient integrated programme is limited. Historically, national and global programmes were focused on the control of only one disease, usually through a comprehensive approach that involved several interventions including PCT. Overcoming the resulting disease-specific structures and thinking, and ensuring that the integrated programme is embedded within the existing health structures, pose considerable challenges to policy makers and implementers wishing to embark on integrated NTD control. By sharing experiences from Uganda, Tanzania, Southern Sudan, and Mozambique, this symposium article aims to outlines key challenges and solutions to assist countries in establishing efficient integrated NTD programmes.     

Clinical features of cerebral schistosomiasis, especially in cerebral and hepatosplenomegalic type

Clinical features of cerebral schistosomiasis type (CST) and hepatosplenic schistosomiasis type (HST), and typical cases of each type were presented. Results of comparative study of clinical symptoms of both type among three countries in Japan, China and Philippines were discussed. CST in Japan and HST in the Philippines showed unique profiles when they were compared with those in other two countries. Although the reason for the difference is not clear, it might be determined by infection burden, pathogenicity of schistosome and/or immune response to the parasite antigen in human hosts.     

A vaccine against Asian schistosomiasis

There is continued transmission of schistosomiasis japonica in China and Philippines despite highly effective control programs that focus on the application of the highly effective drug praziquantel (PZQ). The massive Three Gorges Dam across the Yangtze River in Southern China, soon to be completed, is expected to significantly increase schistosomiasis transmission and introduce the disease into areas currently unaffected. After long-term experience it is generally accepted that PZQ chemotherapy, although the cornerstone of current control programs, does have significant limitations. Furthermore, efficient drug delivery requires a substantial infrastructure to regularly cover all parts of an endemic area. Although there is not yet clear-cut evidence for the existence of PZQ-resistant schistosome strains, decreased susceptibility to the drug has been observed in several countries. As a result, a protective vaccine represents an essential component for the long-term control of schistosomiasis. This article briefly reviews aspects of anti-schistosome protective immunity that are important in the context of vaccine development. The current status in the development of vaccines against Schistosoma japonicum will then be discussed as will new approaches that may improve on the efficacy of available vaccines, and aid in the identification of new targets for immune attack. With new and extensive data becoming available from the S. japonicum genome project, the prospects for developing an effective vaccine are encouraging. The challenges that remain are many but it is crucial that the momentum towards developing effective anti-schistosome vaccines is maintained.     

Historical view of schistosomiasis japonica in Japan: implementation and evaluation of disease-control strategies in Yamanashi Prefecture

We summarized historical aspects of disease control activities targeting schistosomiasis japonica in Kofu basin, Yamanashi Prefecture, Japan. Kofu Basin was one of the biggest endemic foci of schistosomiasis japonica in Japan, and the last place where transmission of Schistosoma japonicum was confirmed in Japan. Because of the most severe endemic situations in Yamanashi, intensive control measures had been implemented by the central as well as the local government. The last human case in Japan was in 1977, which is just before praziquantel being available. Therefore, the main efforts were focused on snail control. Mass examination and mass chemotherapy were implemented, however, the compliance was not so good because of the severe side effects due to the available therapeutics, Stibnal. Along with socioeconomic development after World War II, big changes in land use, life style, and farming led drastic reduction in the disease prevalence in Kofu Basin in the 1960s. A large amount of budget was also used for disease control. Cementing water canals covered more than 95% of paddy fields in Kofu Basin, and this resulted in ecological changes. After elimination of schistosomiasis, environmental repair is the urgent subject in Kofu Basin. Our experiences in Yamanashi contain both good influences and also a lot of reflection. It is important to evaluate each activity in our history before we give intensive cooperation with countries where endemic foci is still present.     

Haemostatic abnormalities in hepatosplenic schistosomiasis mansoni

Hepatosplenic schistosomiasis is a complex immuno-regulatory disease and is major health problem in endemic countries. Acute bleeding is one of its most serious complications and often life-threatening. Clinical studies have demonstrated that the patients with hepatosplenic schistosomiasis are prone to develop complex haemostatic abnormalities that may be linked to the potential risk of bleeding from ruptured esophageal varices in these patients. The deficit in haemostatic parameters is more pronounced with the advancement of the disease and is maximal in the patients with experience of haematomesis. Evidences of enhanced generation of thrombin and plasmin indicate the presence of low-grade DIC in advanced hepatosplenic schistosomiasis, which is considered as a principal cause of haemostatic abnormalities in this endemic disease. Demonstration of procoagulant expression in peripheral blood monocytes of the patients and in the livers, spleens and intestines of S. mansoni-infected mice suggest their possible implication in the causation of DIC in S. mansoni infections. Moreover, because in vitro analysis indicates a participation of immune mechanisms in the localized procoagulant expression, it seems likely that the immune responses to schstosomes play a major role in the pathogenic mechanisms of haemostatic abnormalities in hepatosplenic schistosomiasis.     

Unresolved issues in anthelmintic pharmacology for helminthiases of humans

Helminth infections are an important constraint on the health and development of poor children and adults. Anthelmintic treatment programmes provide a safe and effective response, and increasing numbers of people are benefitting from these public health initiatives. Despite decades of clinical experience with anthelmintics for the treatment of human infections, relatively little is known about their clinical pharmacology. All of the drugs were developed initially in response to the considerable market for veterinary anthelmintics in high- and middle-income countries. In contrast, the greatest burden caused by these infections in humans is in resource-poor settings and as a result there has been insufficient commercial incentive to support studies on how these drugs work in humans, and how they should best be used in control programmes. The advent of mass drug administration programmes for the control of schistosomiasis, lymphatic filariasis, onchocerciasis and soil-transmitted helminthiases in humans increases the urgency to better understand and better monitor drug resistance, and to broaden the currently very narrow range of available anthelmintics. This provides fresh impetus for developing a comprehensive research platform designed to improve our understanding of these important drugs, in order to bring the scientific knowledge base supporting their use to a standard equivalent to that of drugs commonly used in developed countries. Furthermore, a better understanding of their clinical pharmacology will enable improved therapy and could contribute to the discovery of new products.     

Schistosomiasis research in the dongting lake region and its impact on local and national treatment and control in China

Schistosomiasis is a chronic and debilitating parasitic disease that has often been neglected because it is a disease of poverty, affecting poor rural communities in the developing world. This is not the case in the People's Republic of China (PRC), where the disease, caused by Schistosoma japonicum, has long captured the attention of the Chinese authorities who have, over the past 50-60 years, undertaken remarkably successful control programs that have substantially reduced the schistosomiasis disease burden. The Dongting Lake region in Hunan province is one of the major schistosome-endemic areas in the PRC due to its vast marshland habitats for the Oncomelania snail intermediate hosts of S. japonicum. Along with social, demographic, and other environmental factors, the recent completion and closure of the Three Gorges dam will most likely increase the range of these snail habitats, with the potential for re-emergence of schistosomiasis and increased transmission in Hunan and other schistosome-endemic provinces being a particular concern. In this paper, we review the history and the current status of schistosomiasis control in the Dongting Lake region. We explore the epidemiological factors contributing to S. japonicum transmission there, and summarise some of the key research findings from studies undertaken on schistosomiasis in Hunan province over the past 10 years. The impact of this research on current and future approaches for sustainable integrated control of schistosomiasis in this and other endemic areas in the PRC is emphasised.     

A study of the environmental determinants of malaria and schistosomiasis in the Philippines using Remote Sensing and Geographic Information Systems

Malaria and schistosomiasis are two water-related parasitic diseases affecting millions of people worldwide particularly tropical and subtropical countries. In the Philippines, malaria is found in 72 out of 78 provinces while schistosomiasis is endemic in 24 provinces. The Anopheles mosquito and the Oncomelania snail involved in the transmission of these diseases depend on certain environmental determinants that support mosquito and snail populations. This study, done for the first time in the Philippines, successfully showed how Remote Sensing (RS) and Geographical Information Systems (GIS) can be effectively used in showing how these environmental factors affect the spatial distribution of these two diseases. The study sites, i.e. the municipalities of Asuncion and Kapalong, are known endemic sites for both malaria and schistosomiasis. Georeferenced data enabled visualization of prevalence data in relation to physical maps thus facilitating assessment of disease situation in the two municipalities. RS and GIS data proved that other factors aside from climate influence the epidemiology of the diseases in the two sites. Topography and slope as main physical factors influence the vegetation cover, land use and soil type prevailing in particular areas. In addition, water sources especially irrigation networks differed in various places in the study sites in turn affecting the magnitude and distribution of malaria and schistosomiasis. Significant correlations found between the diseases and the environmental variables formed the basis for development of models to predict the disease prevalence in the two municipalities. Proximity to snail breeding sites and irrigation networks and the highly agricultural nature of the barangays were identified as the most common factors that define the high prevalence areas for schistosomiasis confirming the fact that conditions that support the snail populations will in turn favor the presence of the disease. For malaria, the predictive models included temperature, humidity, soil type, predominance of reproduction brush, presence of cultivated areas, distance from deep wells and distance from conventional water source which are in turn influenced by the factor of elevation.