Darren J. Gray

Schistosomiasis elimination: lessons from the past guide the future

Schistosomiasis is a major neglected tropical disease, with more than 200 million people infected and close to 800 million at risk. The disease burden is estimated to exceed 70 million disability-adjusted life-years. The anthelmintic drug praziquantel is highly effective in killing adult schistosome worms, but it is unable to kill developing schistosomes and so does not prevent reinfection. As a result, current praziquantel-based control programmes in Asia and sub-Saharan Africa are not effective or sustainable in the long term. The control of neglected tropical diseases, including schistosomiasis, is a funding priority for several donor agencies, with over US

Diagnosis and management of schistosomiasis

350 million committed until 2013. Here we put forward an argument that donor funds would be more effectively spent on the development of a multi-faceted, integrated control programme, which would have a greater and longer lasting effect on disease transmission than the current chemotherapy-based programmes. The development of a transmission-blocking vaccine is also of great importance. A multi-faceted integrated control programme that incorporates a vaccine, even if only partly effective, has the potential to eliminate schistosomiasis. This integrated-approach model has the potential to improve the health of a billion of the worlds poorest people and its effect cannot be underestimated.

Diagnosis, treatment, and management of echinococcosis

The authors’ studies on schistosomiasis have received financial support from various sources including: the UNICEF/UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases; the National Health and Medical Research Council of Australia; the Wellcome Trust (UK); the Sandler Foundation (USA); the Dana Foundation (USA); and the National Institute of Allergy and Infectious Diseases.

Transmission dynamics of Schistosoma japonicum in the lakes and marshlands of China.

#### Summary points Echinococcosis (hydatid disease) is caused by the larvae of dog and fox tapeworms (cestodes) of the genus Echinococcus (family Taeniidae).1 2 3 This zoonosis is characterised by long term growth of metacestode (hydatid) cysts in humans and mammalian intermediate hosts. The two major species that infect humans are E granulosus and E multilocularis , which cause cystic echinococcosis (CE) and alveolar echinococcosis (AE). A few reported cases of polycystic echinococcosis in Central and South America are caused by E vogeli and E oligarthrus .2 w1 w2 The clinical potential of two other Echinococcus species ( E shiquicus and E felidis ) is unknown.1 2 #### Sources and selection criteria We obtained information from personal reference archives, personal experience, and extensive literature searches of the PubMed and Cochrane databases. We sourced English language papers that were fully published mainly between 2000 and March 2012 using appropriate index terms. …

Application of a Multiplex Quantitative PCR to Assess Prevalence and Intensity Of Intestinal Parasite Infections in a Controlled Clinical Trial

Background Schistosoma japonicum is a major public health concern in China, with over one million people infected and another 40 million living in areas at risk of infection. Unlike the disease caused by S. mansoni and S. haematobium, schistosomiasis japonica is a zoonosis, involving a number of different mammalian species as reservoir hosts. As a result of a number of published reports from China, it has long been considered that bovines, particularly water buffaloes, play a major role in human S. japonicum transmission there, and a drug-based intervention study (1998–2003) around the Poyang Lake in Jiangxi Province provided proof of concept that water buffaloes are, indeed, major reservoirs of human infection in this setting. Methods and Findings In this study we incorporated recently obtained epidemiological information to model the steady-state S. japonicum transmission as well as the impact of the removal of S. japonicum transmission attributable to water buffaloes on human infection rates across six different endemic scenarios within three villages in the Dongting (Hunan) and Poyang (Jiangxi) lakes of southern China. Similar results were obtained for all scenarios. Steady-state S. japonicum infection rates remained constant and human prevalence and incidence were predicted to fall considerably over time. The model showed that the contribution of S. japonicum water buffalo transmission to human infection ranged from 39.1% to 99.1% and predicted that the removal of water buffalo transmission would reduce parasite reproductive rates below 1. This indicates that without the contribution of water buffaloes, S. japonicum transmission is interrupted and unsustainable. These scenarios are generalizable to other endemic villages in the lake and marshland areas of China where a similar cycle of snail infection and infection/reinfection of humans and bovines occurs. Conclusions Along with previous epidemiological data, our findings strongly support water buffaloes as an important component of the transmission cycle that affects humans in the lake and marshlands region of China, a feature which appears to differ from the situation prevalent in the Philippines where their contribution is less pronounced. Our conclusions underscore the rationale for removal, replacement or treatment of water buffaloes, and for the development and deployment of a transmission blocking buffalo vaccine against S. japonicum for this setting to achieve the goal of transmission control. The Chinese Government has recently commenced a new integrated national strategy to improve on existing approaches to control schistosomiasis in the lake and marshlands region by reducing bovines and humans as a source of S. japonicum infection to Oncomelania snails.

A cluster-randomised intervention trial against Schistosoma japonicum in the Peoples' Republic of China: bovine and human transmission.

Background Accurate quantitative assessment of infection with soil transmitted helminths and protozoa is key to the interpretation of epidemiologic studies of these parasites, as well as for monitoring large scale treatment efficacy and effectiveness studies. As morbidity and transmission of helminth infections are directly related to both the prevalence and intensity of infection, there is particular need for improved techniques for assessment of infection intensity for both purposes. The current study aimed to evaluate two multiplex PCR assays to determine prevalence and intensity of intestinal parasite infections, and compare them to standard microscopy. Methodology/Principal Findings Faecal samples were collected from a total of 680 people, originating from rural communities in Timor-Leste (467 samples) and Cambodia (213 samples). DNA was extracted from stool samples and subject to two multiplex real-time PCR reactions the first targeting: Necator americanus, Ancylostoma spp., Ascaris spp., and Trichuris trichiura; and the second Entamoeba histolytica, Cryptosporidium spp., Giardia. duodenalis, and Strongyloides stercoralis. Samples were also subject to sodium nitrate flotation for identification and quantification of STH eggs, and zinc sulphate centrifugal flotation for detection of protozoan parasites. Higher parasite prevalence was detected by multiplex PCR (hookworms 2.9 times higher, Ascaris 1.2, Giardia 1.6, along with superior polyparasitism detection with this effect magnified as the number of parasites present increased (one: 40.2% vs. 38.1%, two: 30.9% vs. 12.9%, three: 7.6% vs. 0.4%, four: 0.4% vs. 0%). Although, all STH positive samples were low intensity infections by microscopy as defined by WHO guidelines the DNA-load detected by multiplex PCR suggested higher intensity infections. Conclusions/Significance Multiplex PCR, in addition to superior sensitivity, enabled more accurate determination of infection intensity for Ascaris, hookworms and Giardia compared to microscopy, especially in samples exhibiting polyparasitism. The superior performance of multiplex PCR to detect polyparasitism and more accurately determine infection intensity suggests that it is a more appropriate technique for use in epidemiologic studies and for monitoring large-scale intervention trials.

Water, Sanitation, and Hygiene (WASH): A Critical Component for Sustainable Soil-Transmitted Helminth and Schistosomiasis Control

Background Zoonotic schistosomiasis japonica is a major public health problem in China. Bovines, particularly water buffaloes, are thought to play a major role in the transmission of schistosomiasis to humans in China. Preliminary results (1998–2003) of a praziquantel (PZQ)-based pilot intervention study we undertook provided proof of principle that water buffaloes are major reservoir hosts for S. japonicum in the Poyang Lake region, Jiangxi Province. Methods and Findings Here we present the results of a cluster-randomised intervention trial (2004–2007) undertaken in Hunan and Jiangxi Provinces, with increased power and more general applicability to the lake and marshlands regions of southern China. The trial involved four matched pairs of villages with one village within each pair randomly selected as a control (human PZQ treatment only), leaving the other as the intervention (human and bovine PZQ treatment). A sentinel cohort of people to be monitored for new infections for the duration of the study was selected from each village. Results showed that combined human and bovine chemotherapy with PZQ had a greater effect on human incidence than human PZQ treatment alone. Conclusions The results from this study, supported by previous experimental evidence, confirms that bovines are the major reservoir host of human schistosomiasis in the lake and marshland regions of southern China, and reinforce the rationale for the development and deployment of a transmission blocking anti-S. japonicum vaccine targeting bovines. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000263291

High prevalence of Schistosoma japonicum infection in Carabao from Samar Province, the Philippines: implications for transmission and control

SJC is funded by an Australian Postgraduate Award and a University of Queensland Advantage Scholarship, ACAC is an Australian National Health and Medical Research Council (NHMRC) Career Development Fellow (631619), RJSM is funded by a Post-doctoral Research Fellowship from the University of Queensland (41795457), JSM is an Australian National Health and Medical Research Council Practitioner Fellow, and DJG is an Australian Research Council (DECRA) Fellow. This work is funded by an NHMRC Partnership project in collaboration with WaterAid Australia.

Conquering 'snail fever': Schistosomiasis and its control in China

Schistosoma japonicum is endemic in the Philippines, China and Indonesia, and infects more than 40 mammalian host species, all of which can act as reservoirs of infection. In China, water buffaloes have been shown to be major reservoirs of human infection. However, in the Philippines, carabao have not been considered important reservoir hosts for S. japonicum due to the low prevalence and infection intensities reported, the only exception being a qPCR-based study indicating 51% of carabao were S. japonicum-positive. However, the low prevalence found for the same animals when using conventional copro-parasitological techniques means that there is still confusion about the role of carabao in the transmission of schistosomiasis japonicum. To address this inconsistency, and to shed light on the potential role of carabao in the transmission of S. japonicum in the Philippines, we undertook a pilot survey, collecting fecal samples from animals in Western Samar Province and we used a combination of molecular and copro-parasitological techniques to determine the prevalence and intensity of S. japonicum. We found a high prevalence of S. japonicum in the carabao using a validated real-time PCR (qPCR) and a copro-parasitological tool, the formalin-ethyl acetate sedimentation (FEA-SD) technique. A much lower prevalence of S. japonicum was recorded for the same fecal samples using conventional PCR, the Kato-Katz technique and miracidial hatching. These results suggest that, due to their low diagnostic sensitivity, traditional copro-parasitological techniques underestimate infection in carabao. The use of FEA-SD and qPCR provides a more accurate diagnosis. Based on these findings, the role of bovines in the transmission of S. japonicum appears to be more important in the Philippines than previously recognized, and this may have significant implications for the future control of schistosomiasis there, particularly as, in contrast with previous surveys, we found an unprecedented high prevalence of S. japonicum in humans.

Schistosomiasis research in the Dongting Lake Region and its impact on local and national treatment and control in China

Schistosomiasis japonica is a serious parasitic disease and a major health risk for more than 60 million people living in the tropical and subtropical zones of south China. The disease is a zoonosis and its cause, the parasitic trematode Schistosoma japonicum, has a range of mammalian reservoirs, making control efforts difficult. Current control programs are heavily based on community chemotherapy with a single dose of the highly effective drug praziquantel. However, vaccines (for use in bovines and in humans) in combination with other control strategies are needed to eliminate the disease. In this review, we provide an overview of the transmission, clinical features, pathogenesis, diagnosis, treatment, genetics and susceptibility, epidemiology, and prospects for control of schistosomiasis japonica in China. The threat posed by the Three Gorges Dam may undermine control efforts because it will change the local ecology and associated schistosomiasis transmission risks over the next decade and beyond.