David Rollinson

Time to set the agenda for schistosomiasis elimination

It is time to raise global awareness to the possibility of schistosomiasis elimination and to support endemic countries in their quest to determine the most appropriate approaches to eliminate this persistent and debilitating disease. The main interventions for schistosomiasis control are reviewed, including preventive chemotherapy using praziquantel, snail control, sanitation, safe water supplies, and behaviour change strategies supported by information, education and communication (IEC) materials. Differences in the biology and transmission of the three main Schistosoma species (i.e. Schistosoma haematobium, S. mansoni and S. japonicum), which impact on control interventions, are considered. Sensitive diagnostic procedures to ensure adequate surveillance in areas attaining low endemicity are required. The importance of capacity building is highlighted. To achieve elimination, an intersectoral approach is necessary, with advocacy and action from local communities and the health community to foster cooperative ventures with engineers, the private sector, governments and non-governmental organizations specialized in water supply and sanitation. Examples of successful schistosomiasis control programmes are reviewed to highlight what has been learnt in terms of strategy for control and elimination. These include St. Lucia and other Caribbean islands, Brazil and Venezuela for S. mansoni; Saudi Arabia and Egypt for both S. mansoni and S. haematobium; Morocco, Tunisia, Algeria, Mauritius and the Islamic Republic of Iran for S. haematobium; Japan and the Peoples Republic of China for S. japonicum. Additional targets for elimination or even eradication could be the two minor human schistosome species S. guineenisis and S. intercalatum, which have a restricted distribution in West and Central Africa. The examples show that elimination of schistosomiasis is an achievable and desirable goal requiring full integration of preventive chemotherapy with the tools of transmission control. An agenda for the elimination of schistosomiasis would aim to identify the gaps in knowledge, and define the tools, strategies and guidelines that will help national control programmes move towards elimination, including an internationally accepted mechanism that allows verification/confirmation of elimination.

Whole-genome sequence of Schistosoma haematobium

Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide. No vaccines are available, and treatment relies on one drug, praziquantel. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer and as a predisposing factor for HIV/AIDS. The parasite is transmitted to humans from freshwater snails. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease and induce squamous cell carcinoma. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.

Diagnosis of Soil-Transmitted Helminths in the Era of Preventive Chemotherapy: Effect of Multiple Stool Sampling and Use of Different Diagnostic Techniques

Background Soil-transmitted helminth infections are common throughout the tropics and subtropics and they disproportionately affect the poorest of the poor. In view of a growing global commitment to control soil-transmitted helminthiasis, there is a need to elucidate the effect of repeated stool sampling and the use of different diagnostic methods in areas targeted for preventive chemotherapy that are characterized by low-infection intensities. In this study, we focused on schoolchildren on Unguja Island, Zanzibar, an area where anthelminthic drugs have been repeatedly administered over the past decade. Methodology/Principal Findings Three serial stool samples from each of 342 schoolchildren were examined using the Kato-Katz (K-K), Koga agar plate (KAP), and Baermann (BM) techniques. These methods were used individually or in combination for the diagnosis of Ascaris lumbricoides (K-K), Trichuris trichiura (K-K), hookworm (K-K and KAP), and Strongyloides stercoralis (KAP and BM). The examination of multiple stool samples instead of a single one resulted in an increase of the observed prevalence; e.g., an increase of 161% for hookworm using the K-K method. The diagnostic sensitivity of single stool sampling ranged between 20.7% for BM to detect S. stercoralis and 84.2% for K-K to diagnose A. lumbricoides. Highest sensitivities were observed when different diagnostic approaches were combined. The observed prevalences for T. trichiura, hookworm, A. lumbricoides, and S. stercoralis were 47.9%, 22.5%, 16.5%, and 10.8% after examining 3 stool samples. These values are close to the ‘true’ prevalences predicted by a mathematical model. Conclusion/Significance Rigorous epidemiologic surveillance of soil-transmitted helminthiasis in the era of preventive chemotherapy is facilitated by multiple stool sampling bolstered by different diagnostic techniques.

The phylogeny of the Schistosomatidae based on three genes with emphasis on the interrelationships of Schistosoma Weinland, 1858.

Schistosomes are digenean flukes, parasitic of birds, mammals and crocodiles. The family Schistosomatidae contains species of considerable medical and veterinary importance, which cause the disease schistosomiasis. Previous studies, both morphological and molecular, which have provided a good deal of information on the phylogenetics of this group, have been limited in the number of species investigated or the type or extent of molecular data used. This paper presents the most comprehensive phylogeny to date, based on the sequences of 3 genes, complete ribosomal small subunit rRNA and large ribosomal subunit rRNA, and mitochondrial cytochrome oxidase 1, sequenced from 30 taxa including at least 1 representative from 10 of the 13 known genera of the Schistosomatidae and 17 of the 20 recognized Schistosoma species. The phylogeny is examined using morphological characters, intermediate and definitive host associations and biogeography. Theories as to the origins and spread of Schistosoma are also explored. The principal findings are that Ornithobilharzia and Austrobilharzia form a sister group to the Schistosoma; mammalian schistosomes appear paraphyletic and 2 Trichobilharzia species, T. ocellata and T. szidati, seem to be synonymous. The position of Orientobilharzia within the Schistosoma is confirmed, as is an Asian origin for the Schistosoma, followed by subsequent dispersal through India and Africa.

Widespread vertical transmission and associated host sex ratio distortion within the eukaryotic phylum Microspora

Vertical transmission (VT) and associated manipulation of host reproduction are widely reported among prokaryotic endosymbionts. Here, we present evidence for widespread use of VT and associated sex–ratio distortion in a eukaryotic phylum. The Microspora are an unusual and diverse group of eukaryotic parasites that infect all animal phyla. Following our initial description of a microsporidian that feminizes its crustacean host, we survey the diversity and distribution of VT within the Microspora. We find that vertically transmitted microsporidia are ubiquitous in the amphipod hosts sampled and that they are also diverse, with 11 species of microsporidia detected within 16 host species. We found that infections were more common in females than males, suggesting that host sex–ratio distortion occurs in five out of eight parasite species tested. Phylogenetic reconstruction demonstrates that VT occurs in all major lineages of the phylum Microspora and that sex–ratio distorters are found on multiple branches of the phylogenetic tree. We propose that VT is either an ancestral trait or evolves with peculiar frequency in this phylum. If the association observed here between VT and host sex–ratio distortion holds true across other host taxa, these eukaryotic parasites may join the bacterial endosymbionts in their importance as sex–ratio distorters.

Implementation of Human Schistosomiasis Control: Challenges and Prospects

Schistosomiasis is a major disease of public health importance in humans occurring in over 70 countries of the tropics and sub-tropics. In this chapter, the history of the control of schistosomiasis is briefly discussed and current methods of control of schistosomiasis are reviewed; including mollusciciding, biological control of the intermediate snail hosts, the development of drugs to kill the adult worms, provision of clean water and health education, with a focus on the African situation. Since an effective vaccine against schistosomiasis is lacking, the emphasis today is placed on the drug praziquantel (PZQ). The marked reduction in the cost of PZQ together with the support of the Bill and Melinda Gates Foundation has enabled the drug to be used more widely in sub-Saharan Africa. Nevertheless, with the possibility of resistance to praziquantel emerging, the potential role of other drugs, such as artemether, in the control of schistosomiasis is examined. The World Health Organization (WHO) anticipates that at least 75% of all schoolchildren at risk of morbidity from schistosomiasis will be treated by 2010, with the aim of reversing morbidity. The importance of recent international initiatives such as the Schistosomiasis Control Initiative (SCI) working in Mali, Niger, Burkina Faso, Zambia, Tanzania and Uganda is recognised. There are benefits to integrating the control of schistosomiasis with other disease control programmes, such as gastrointestinal helminths and/or lymphatic filariasis (LF), since this markedly reduces the cost of delivery of the treatment. Countries that are situated on the perimeter of the distribution of schistosomiasis have either achieved or have made progress towards the elimination of the disease. For control programmes to be successful in areas such as sub-Saharan Africa, it is absolutely essential that these programmes are sustainable. Thus, it will be vital for Ministries of Health and Education to budget for the control of diseases of poverty in addition to school health, and to utilise funds from a range of sources, such as, government funds, pooled donor contributions, or bilateral and international agencies.

A wake up call for urinary schistosomiasis: reconciling research effort with public health importance

This review considers the current status of urinary schistosomiasis, caused by infection with Schistosoma haematobium, and argues that greater research effort and focus are needed to improve understanding of this neglected tropical disease (NTD). The inappropriateness of relying solely on data concerning the much more extensively studied intestinal form of schistosomiasis caused by S. mansoni is highlighted. The current lack of genome and transcriptome information for S. haematobium is directly hindering further targeted research and must be quickly rectified. Recent molecular phylogenies caution the expectation of similarities between schistosome species and highlight the close relationships of species within the S. haematobium group. Treatment, current and prospective drugs and vaccines, together with diagnosis are considered, highlighting the differences associated with urinary schistosomiasis. This infection has a significant and specific impact on the urino-genital system and has a strong association with bladder cancer, leading to severe and chronic morbidity. There is a clear need for new clinical initiatives in this area to better quantify the disease burden. Furthermore, emerging associations with HIV and other pathogens need to be closely monitored. Research is urgently needed to improve current knowledge in order to develop the next generation of control tools.

Bidirectional Introgressive Hybridization between a Cattle and Human Schistosome Species

Schistosomiasis is a disease of great medical and veterinary importance in tropical and subtropical regions, caused by parasitic flatworms of the genus Schistosoma (subclass Digenea). Following major water development schemes in the 1980s, schistosomiasis has become an important parasitic disease of children living in the Senegal River Basin (SRB). During molecular parasitological surveys, nuclear and mitochondrial markers revealed unexpected natural interactions between a bovine and human Schistosoma species: S. bovis and S. haematobium, respectively. Hybrid schistosomes recovered from the urine and faeces of children and the intermediate snail hosts of both parental species, Bulinus truncatus and B. globosus, presented a nuclear ITS rRNA sequence identical to S. haematobium, while the partial mitochondrial cox1 sequence was identified as S. bovis. Molecular data suggest that the hybrids are not 1st generation and are a result of parental and/or hybrid backcrosses, indicating a stable hybrid zone. Larval stages with the reverse genetic profile were also found and are suggested to be F1 progeny. The data provide indisputable evidence for the occurrence of bidirectional introgressive hybridization between a bovine and a human Schistosoma species. Hybrid species have been found infecting B. truncatus, a snail species that is now very abundant throughout the SRB. The recent increase in urinary schistosomiasis in the villages along the SRB could therefore be a direct effect of the increased transmission through B. truncatus. Hybridization between schistosomes under laboratory conditions has been shown to result in heterosis (higher fecundity, faster maturation time, wider intermediate host spectrum), having important implications on disease prevalence, pathology and treatment. If this new hybrid exhibits the same hybrid vigour, it could develop into an emerging pathogen, necessitating further control strategies in zones where both parental species overlap.

Comparative cost assessment of the Kato-Katz and FLOTAC techniques for soil-transmitted helminth diagnosis in epidemiological surveys.

BackgroundThe Kato-Katz technique is widely used for the diagnosis of soil-transmitted helminthiasis in epidemiological surveys and is believed to be an inexpensive method. The FLOTAC technique shows a higher sensitivity for the diagnosis of light-intensity soil-transmitted helminth infections but is reported to be more complex and expensive. We assessed the costs related to the collection, processing and microscopic examination of stool samples using the Kato-Katz and FLOTAC techniques in an epidemiological survey carried out in Zanzibar, Tanzania.MethodsWe measured the time for the collection of a single stool specimen in the field, transfer to a laboratory, preparation and microscopic examination using standard protocols for the Kato-Katz and FLOTAC techniques. Salaries of health workers, life expectancy and asset costs of materials, and infrastructure costs were determined. The average cost for a single or duplicate Kato-Katz thick smears and the FLOTAC dual or double technique were calculated.ResultsThe average time needed to collect a stool specimen and perform a single or duplicate Kato-Katz thick smears or the FLOTAC dual or double technique was 20 min and 34 sec (20:34 min), 27:21 min, 28:14 min and 36:44 min, respectively. The total costs for a single and duplicate Kato-Katz thick smears were US

Albendazole and Mebendazole Administered Alone or in Combination with Ivermectin against Trichuris trichiura: A Randomized Controlled Trial

1.73 and US