The epidemiology of morbidity of schistosomiasis

The epidemiology of schistosomiasis is changing because treatment of chronically infected individuals is often followed by reinfection. As a major goal of schistosomiasis control is the reduction of morbidity, direct assessment of disease is essential because infection status is a relatively poor indication of morbidity. Introduction of ultrasonography to the study of schistosomiasis and the increased appreciation of the effects of schistosomiasis on growth and development in children have greatly enhanced our understanding of schistosome-induced morbidity in endemic communities. Peter Wiest here reviews the changes in the assessment of schistosomiasis-induced morbidity.     

Urogenital schistosomiasis infection prevalence targets to determine elimination as a public health problem based on microhematuria prevalence in school-age children

BackgroundRecent research suggests that schistosomiasis targets for morbidity control and elimination as a public health problem could benefit from a reanalysis. These analyses would define evidence-based targets that control programs could use to confidently assert that they had controlled or eliminated schistosomiasis as a public health problem. We estimated how low Schistosoma haematobium infection levels diagnosed by urine filtration in school-age children should be decreased so that microhematuria prevalence was at, or below, a “background” level of morbidity.MethodologyData obtained from school-age children in Burkina Faso, Mali, Niger, Tanzania, and Zambia who participated in schistosomiasis monitoring and evaluation cohorts were reanalyzed before and after initiation of preventive chemotherapy. Bayesian models estimated the infection level prevalence probabilities associated with microhematuria thresholds ≤10%, 13%, or 15%.Principal findingsAn infection prevalence of 5% could be a sensible target for urogenital schistosomiasis morbidity control in children as microhematuria prevalence was highly likely to be below 10% in all surveys. Targets of 8% and 11% infection prevalence were highly likely to result in microhematuria levels less than 13% and 15%, respectively. By contrast, measuring heavy-intensity infections only achieves these thresholds at impractically low prevalence levels.Conclusions/significanceA target of 5%, 8%, or 11% urogenital schistosomiasis infection prevalence in school-age children could be used to determine whether a geographic area has controlled or eliminated schistosomiasis as a public health problem depending on the local background threshold of microhematuria.     

Achievements of schistosomiasis control in China

The control of schistosomiasis has been spectacularly successful in terms of controlling endemicity and severity of the disease during the last 50 years. It can be categorized into two stages. From 1955 through 1980, the transmission-control strategy had been widely and successfully carried out. By the end of 1980, the epidemic of schistosomiasis was successfully circumscribed in certain core regions including areas at the middle and low reaches of the Yangtze River and some mountainous areas in Sichuan and Yunnan provinces, where control of schistosomiasis had been demonstrated to be very difficult to be sustained. Therefore, since 1980, schistosomiasis control in China has been modified to employ a stepwise strategy, based on which morbidity control has been given priorities and if possible transmission control has been pursued. However, since snail-ridden areas remain unchanged so far, reinfections occur frequently. This necessitates a maintenance phase to consolidate the achievements in the control of schistosomiasis. In the mean time, we are challenged with some environmental, social and economical changes in terms of controlling schistosomiasis. Successfully controlling schistosomiasis in China is still a long-term task but will be achieved without doubt along with the economic development and the promotion of living and cultural standard of people.     

Immunoregulation and World Health Assembly resolution 54.19: why does treatment control morbidity?

World Health Assembly resolution 54.19, passed in May, 2001, declares the intent of the World Health Organization member States to implement a combined strategy for the control of morbidity caused by schistosomiasis and soil-transmitted helminths. Among other things, the resolution urges ministries to treat all clinical cases and groups at high risk of morbidity such as children, women and those exposed occupationally. The policy is predicated on the evidence that morbidity due to these infections can be controlled by periodic treatment with appropriate chemotherapeutic, anti-helminthic drugs. While it is true that annual or biannual praziquantel treatment for schistosomiasis decreases morbidity, we now question how treatment leads to this beneficial effect. It is clear that treatment kills worms, but we propose that this is only a part of how it leads to reduced morbidity in areas of ongoing transmission and reinfection. By killing worms, we postulate that treatment also effects immunologic changes to the normal host/parasite relationship, and the resulting immune responses lead to both increased resistance (protection against reinfection), and increased immunoregulatory mechanisms that control morbidity upon subsequent reinfections. If the effects of treatment contribute to morbidity control in these ways, a better understanding of how this occurs may allow optimization of these effects of treatment through appropriate periodic treatment regimens, resulting in less reinfection and better morbidity control when reinfection does occur.     

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.     

Biotechnological advances in the diagnosis,species differentiation and phylogenetic analysis of Schistosoma spp.

Schistosomiasis is a serious parasitic disease caused by blood-dwelling flukes of the genus Schistosoma. Throughout the world, schistosomiasis is associated with high rates of morbidity and mortality, with close to 800 million people at risk of infection. Precise methods for identification of Schistosoma species and diagnosis of schistosomiasis are crucial for an enhanced understanding of parasite epidemiology that informs effective antiparasitic treatment and preventive measures. Traditional approaches for the diagnosis of schistosomiasis include etiological, immunological and imaging techniques. Diagnosis of schistosomiasis has been revolutionized by the advent of new molecular technologies to amplify parasite nucleic acids. Among these, polymerase chain reaction-based methods have been useful in the analysis of genetic variation among Schistosoma spp. Mass spectrometry is now extending the range of biological molecules that can be detected. In this review, we summarize traditional, non-DNA-based diagnostic methods and then describe and discuss the current and developing molecular techniques for the diagnosis, species differentiation and phylogenetic analysis of Schistosoma spp. These exciting techniques provide foundations for further development of more effective and precise approaches to differentiate schistosomes and diagnose schistosomiasis in the clinic, and also have important implication for exploring novel measures to control schistosomiasis in the near future.     

Schistosoma mansoni-Related Hepatosplenic Morbidity in Adult Population on Kome Island,Sengerema District,Tanzania

Schistosomiasis is one of the important neglected tropical diseases (NTDs) in Tanzania, particularly in Lake Victoria zone. This baseline survey was a part of the main study of integrated control of schistosomiasis and soil-transmitted helminths (STHs) aimed at describing morbidity patterns due to intestinal schistosomiasis among adults living on Kome Island, Sengerema District, Tanzania. Total 388 adults from Kome Islands (about 50 people from each village) aged between 12 and 85 years, were examined by abdominal ultrasound according to the Niamey protocol. Liver image patterns (LIPs) A and B were considered normal, and C-F as distinct periportal fibrosis (PPF). The overall prevalence of PPF was 42.2%; much higher in males than in females (47.0% in male vs 34.4% in females, P=0.007). Abnormal increase of segmental branch wall thickness (SBWT) and dilated portal vein diameter (PVD) were also more common in males than in females. Hepatosplenomegaly was frequently encountered; 68.1% had left liver lobe hepatomegaly and 55.2% had splenomegaly. Schistosoma mansoni-related morbidity is quite high among adults in this community justifying the implementation of integrated control strategies through mass drug administration, improved water supply (pumped wells), and health education that had already started in the study area.     

Screening for schistosomiasis with questionnaires

New schistosomiasis control initiatives have been launched to reduce significantly the current global burden of this disease, mainly through regular administration of praziquantel to schoolchildren living in endemic areas. Because schistosomiasis is distributed focally, epidemiological tools for rapid and inexpensive identification of communities at highest risk of morbidity are required to target praziquantel most efficiently. This article outlines the development and validation of simple questionnaires for screening of Schistosoma haematobium and Schistosoma mansoni in sub-Saharan Africa.     

Progress in the prevention and control of schistosomiasis and soil-transmitted helminthiasis

In the last two decades important progress has been made in the understanding the epidemiology and the disease burden of schistosomiasis and soil-transmitted nematodes infection. In addition, practical tools for disease control have been developed and a strategy for the prevention and control of morbidy of schistosomaisis and soil-transmitted nematodes infection has been endorsed by the World Health Organization. This paper presents the recent progress in the prevention and control of these infections: the estimates of chronic and subtle morbidity in high risk groups and the evidence that these chronic and severe sequelae of infections can be reversed by appropriate treatment; the use of anthelminthic drugs during pregnancy and lactation; the relevance to control morbidity due to these infections also in pre-school children; the efficacy of anthelminthic drugs and the possible threat of drug resistance; price, quality and accessibility of treatment by delivering drugs through the school system and ways of reaching also non-enrolled school-age children. Finally, the strategy, targets and recommendations of the World Health Organization for the control of schistosomiasis and soil-transmitted nematodes infection are described.     

Schistosomiasis mekongi: from discovery to control

In the Mekong River basin, the first case of schistosomiasis was reported in 1957. In the 1960s, endemic areas of the infection, of which profiles were similar to those of schistosomiasis japonica, were discovered in Khong Island, Laos, to Kratie province, Cambodia. A new intermediate snail host; Neotricula aperta was identified and the Mekong strain of schistosome was elevated to a new species: Schistosoma mekongi in 1978. Baseline epidemiological surveillance was performed and schistosomiasis mekongi was described as a public health implication in the middle Mekong River basin. Because of political and economical confusion, endemic situation had become worse, and no control program had been implemented until mass treatment program with praziquantel on Khong Island in 1983. Since then, the prevalence of S. mekongi infection has rapidly decreased in each endemic area. Serological diagnosis has been useful to detect new but low endemic foci. Clinical manifestations of S. mekongi infection are similar to those of S. mansoni and S. japonicum infections. As the reduction of prevalence and intensity of S. mekongi infection, morbidity due to the disease has changed, and ultrasonographic examination is now useful to evaluate morbidity due to schistosomiasis mekongi. Transmission of the disease occurs in a couple of months during low water season. Control of N. aperta is difficult and long-lasting effective control measurements have, so far, not been available. In the next step for controling S. mekongi infection, mass treatment should be continued, and it is needed to combine other appropriate control activities.     

Drugs for the control of parasitic diseases: current status and development in schistosomiasis

The morbidity caused by schistosomiasis has been controlled in China, Egypt and the Philippines mainly by the widespread use of the safe and efficacious drug praziquantel (PZQ), and by oxamniquin and PZQ in Brazil. To date, there is no evidence of development of clinically relevant resistance. Thanks to the commitment of national governments at the World Health Assembly in 2001, and the emergence of significant funding for control, it is predicted that there will soon be more widespread use of PZQ in sub-Saharan Africa, where morbidity due to schistosomiasis is most prevalent. There are currently no available alternative drugs to PZQ (with the possible exception of oxamniquin), although perhaps PZQ analogues could be developed. Artemether, used to control malaria, is effective against immature schistosomes, but is less effective against adult worms. The efficacy of myrrh, recently marketed as an antischistosomacide in Egypt, has not been independently confirmed.     

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.     

Morbidity of Schistosomiasis mansoni in the state of Minas Gerais, Brazil

From 2002 to 2005, a program of active search for patients with hepatosplenic schistosomiasis and schistosomal myeloradiculopathy has been implemented in the state of Minas Gerais by the local Health Department. The state was divided in 28 regional health centers and the local representatives have been trained to identify and direct patients with hepatosplenic schistosomiasis and neuroschistosomiasis to a reference center in Belo Horizonte, the capital of the state of Minas Gerais. Seventy five patients with hepatosplenic schistosomiasis and 54 with schistosomal myeloradiculopathy have been referred and examined in the reference center in a period of time of 3 years. Schistosomal myeloradiculopathy should be emphasized because the number of cases reported is increasing rapidly and when timely diagnosed and treated, they respond promptly to treatment. Left untreated, they die or become invalid for life. In our view, the time has come for more active investigation of the different aspects of morbidity caused by schistosomiasis mansoni in Brazil.     

Immunological and parasitological parameters after treatment with dexamethasone in murine Schistosoma mansoni

This work aimed to evaluate the effect of diphenyl dimethyl bicarboxylate (DDB) and dexamethasone alone and in combination with praziquantel on various parasitological, immunological and pathological parameters reflecting disease severity and morbidity in murine schistosomiasis. DDB and dexamethasone had no effect on worm burden but altered tissue egg distribution. This indicates that, under the schedule used, neither drug interfered with the development of adult worms or oviposition, but both can modulate liver pathology. Dexamethasone resulted in a greater reduction in granuloma size than did DDB. Dexamethasone-treated mice also showed lower levels of serum gamma interferon (IFN-γ), interleukin-12 (IL-12) and IL-4, together with higher IL-10 levels, than infected untreated control animals. These data suggest that dexamethasone is a convenient and promising coadjuvant agent that results in decreased morbidity in murine schistosomiasis.     

Low Levels of Awareness Despite High Prevalence of Schistosomiasis among Communities in Nyalenda Informal Settlement,Kisumu City,Western Kenya

Introduction

Intestinal schistosomiasis is widely distributed around Lake Victoria in Kenya where about 16 million people in 56 districts are at risk of the infection with over 9.1 million infected. Its existence in rural settings has been extensively studied compared to urban settings where there is limited information about the disease coupled with low level of awareness. This study therefore assessed community awareness on existence, signs and symptoms, causes, transmission, control and risk factors for contracting schistosomiasis as well as attitudes, health seeking behaviour and environmental antecedents that affect its control so as to identify knowledge gaps that need to be addressed in order to strengthen schistosomiasis control interventions in informal urban settings.

Methods

The study was carried out in an informal urban settlement where the prevalence of intestinal schistosomiasis was previously reported to be the highest (36%) among the eight informal settlements of Kisumu city. The study adopted cross-sectional design and purposive sampling technique. Eight focus group discussions were conducted with adult community members and eight key informant interviews with opinion leaders. Data was audio recorded transcribed, coded and thematically analyzed using ATLAS.ti version 6 software.

Results

Most respondents stated having heard about schistosomiasis but very few had the correct knowledge of signs and symptoms, causes, transmission and control of schistosomiasis. However, there was moderate knowledge of risk factors and at high risk groups. Their attitudes towards schistosomiasis and its control were generally indifferent with a general belief that they had no control over their environmental circumstances to reduce transmission.

Discussion/Conclusion

Although schistosomiasis was prevalent in the study area, majority of the people in the community had low awareness. This study, therefore, stresses the need for health education to raise community''s awareness on schistosomiasis in such settings in order to augment prevention, control and elimination efforts.     

Epidemiology of malaria, schistosomiasis, geohelminths, anemia and malnutrition in the context of a demographic surveillance system in northern Angola

Background

Malaria, schistosomiasis and geohelminth infection are linked to maternal and child morbidity and mortality in sub-Saharan Africa. Knowing the prevalence levels of these infections is vital to guide governments towards the implementation of successful and cost-effective disease control initiatives.

Methodology/Principal Findings

A cross-sectional study of 1,237 preschool children (0–5 year olds), 1,142 school-aged children (6–15 year olds) and 960 women (>15 year olds) was conducted to understand the distribution of malnutrition, anemia, malaria, schistosomiasis (intestinal and urinary) and geohelminths in a north-western province of Angola. We used a recent demographic surveillance system (DSS) database to select and recruit suitable households. Malnutrition was common among children (23.3% under-weight, 9.9% wasting and 32.2% stunting), and anemia was found to be a severe public health problem (i.e., >40%). Malaria prevalence was highest among preschool children reaching 20.2%. Micro-hematuria prevalence levels reached 10.0% of preschool children, 16.6% of school-aged children and 21.7% of mothers. Geohelminth infections were common, affecting 22.3% of preschool children, 31.6% of school-aged children and 28.0% of mothers.

Conclusions

Here we report prevalence levels of malaria, schistosomiasis and geohelminths; all endemic in this poorly described area where a DSS has been recently established. Furthermore we found evidence that the studied infections are associated with the observed levels of anemia and malnutrition, which can justify the implementation of integrated interventions for the control of these diseases and morbidities.     

A Bayesian-based approach for spatio-temporal modeling of county level prevalence of Schistosoma japonicum infection in Jiangsu province, China

Spatio-temporal variations of Schistosoma japonicum infection risk in Jiangsu province, China, were examined and the relationships between key climatic factors and infection prevalence at the county level were determined. The parasitological data were collected annually by means of cross-sectional surveys carried out in 47 counties from 1990 to 1998. Climatic factors, namely land surface temperature (LST) and normalized difference vegetation index (NDVI), were obtained from remote sensing satellite sensors. Bayesian spatio-temporal models were employed to analyze the data. The best fitting model showed that spatial autocorrelation in Jiangsu province decreased dramatically from 1990 to 1992 and increased gradually thereafter. A likely explanation of this finding arises from the large-scale administration of praziquantel for morbidity control of schistosomiasis. Our analysis suggested a negative association between NDVI and risk of S. japonicum infection. On the other hand, an increase in LST contributed to a significant increase in S. japonicum infection prevalence. We conclude that combining geographic information system, remote sensing and Bayesian-based statistical approaches facilitate integrated risk modeling of S. japonicum, which in turn is of relevance for allocation of scarce resources for control of schistosomiasis japonica in Jiangsu province and elsewhere in China, where the disease remains of public health and economic significance.     

Establishing and Applying a Schistosomiasis Early Warning Index (SEWI) in the Lower Yangtze River Region of Jiangsu Province,China

Background

China has made remarkable progress in schistosomiasis control over the past decades. Transmission control has replaced morbidity control as the country moves towards the goal of elimination and the current challenge is to find a sensitive measure capable of gauging transmission risk in low-prevalence areas. The study aims to develop a Schistosomiasis Early Warning Index (SEWI) and demonstrate its use in Jiangsu Province along the lower Yangtze River.

Methodology/Principal Findings

The Delphi approach, a structured communication technique, was used to develop the SEWI. Two rounds of interviews with 30 public health experts specialized in schistosomiasis control were conducted using 40 indicators that reflected different aspects of schistosomiasis transmission and control. The necessity, feasibility, and sensitivity of each indicator were assessed and the weight value of each indicator determined based on these experts'' judgment. The system included 3 first-order indicators, 7 second-order indicators, and 30 third-order indicators. The 3 first-order indicators were endemic status, control measures, social and environmental factors, with the weight values 0.366, 0.343 and 0.291, respectively. For the 7 second-order indicators, the highest weight value was for control measures for snails (0.175) and the lowest for transmission route (0.110). We estimated and mapped the SEWI for endemic areas at the county scale in Jiangsu Province finding that the majority of the endemic areas were characterized as medium transmission risk (SEWI risk values between 0.3 and 0.6), while areas where transmission interruption had been officially declared showed SEWI values <0.30. A few isolated areas (e.g. endemic islands in the Yangtze River) produced SEWI values >0.60. These estimates are largely in agreement with the endemicity levels based on recent epidemiological surveys.

Conclusions/Significance

The SEWI should be useful for estimation of schistosomiasis transmission surveillance, particularly with reference to the elimination of the disease in China.     

The Schistosoma japonicum self-cure phenomenon in water buffaloes: potential impact on the control and elimination of schistosomiasis in China

Schistosomiasis japonica, caused by Schistosoma japonicum, is an important zoonotic disease in China, the Philippines and small pockets of Indonesia. In addition to infecting people, S. japonicum can infect over 40 species of wild and domestic animals which have varying impacts on human infection. It is now generally accepted that bovines, particularly water buffaloes, are the major reservoir for human infection in China as they are naturally infected with schistosomes and deposit more eggs into the environment than humans or any other animal host. This complicates control efforts and the economic burden associated with schistosomiasis morbidity and mortality has taken its toll on both human and livestock populations. Over the last 50 years, the schistosomiasis control program in China has made great strides in reducing prevalence and morbidity, and the Chinese authorities now aim to eliminate the disease nationwide in the next decade. Current Chinese control strategies place particular importance on interventions targeting bovines including: praziquantel treatment, barrier farming to prevent grazing in transmission areas, their replacement with mechanized tractors and possible bovine vaccination. A number of studies have shown that in the period following S. japonicum infection, the worm burden drops sharply in water buffaloes and some other animal hosts such as pigs. This is due to a self-cure phenomenon whereby there is parasite clearance by both immune and non-immune factors. Here we review studies investigating the self-cure effect, paying particular attention to S. japonicum infection in water buffaloes, and discuss its potential impact on the future schistosomiasis control and elimination efforts in China. Further understanding of the mechanism of self-cure in water buffaloes could be important for future schistosome vaccine design and delivery.     

Insights into the mode of action of 1,2,6,7-tetraoxaspiro [7.11] nonadecane (N-89) against adult Schistosoma mansoni worms

Control of morbidity associated with schistosomiasis via chemotherapy largely relies on the drug praziquantel. Repeated therapy with praziquantel has created concerns about the possible selection of resistant worms and necessitated the search for novel drugs to treat schistosomiasis. Here, a murine model was infected with Schistosoma mansoni and treated with oral 1,2,6,7-tetraoxaspiro [7.11] nonadecane (N-89), which caused a significant reduction in fecundity and egg burden and reduced morbidity when administered at 5-weeks post-infection.The analysis showed that the mode of action occurred through the ingestion of activated N-89 by the worms, and that there was no direct external effect on the S. mansoni worms. Ultrastructural analysis of the treated worms showed disruptions in the gut lumen and the presence of large volumes of material, suggestive of undigested blood meals or red blood cells. In addition, there were reduced vitelline cells in female worms and damage to sub-tegmental musculature in male worms. Eggs recovered from the treated mice showed both damage to the eggs and the production of immature eggs. Expression of mRNA responsible for gut and digestive function and egg production was also significantly affected by N-89 treatment, whereas control genes for musculature showed no significant changes.Thus, N-89 drastically affected the total digestive function and egg production of S. mansoni worms. Physiological processes requiring heme uptake such as egg production and eggshell formation were subsequently affected, suggesting that the compound could be a possible therapeutic drug candidate for schistosomiasis control.