Scientific meeting of The Malacological Society of London, held on Thursday 28th April 2005
Children holding red urine samples, a visual sign indicative of S. haematobium infection. (Courtesy of SCI)
Dr Russell Stothard (r.st...@nhm.ac.uk) warmly welcomed everyone to Burlington House for this afternoon scientific meeting held jointly with The Royal Society of Tropical Medicine and Hygiene and The Linnean Society of London to learn more about snail-borne diseases. By uniting aspects of their epidemiology and natural history, the meeting hoped to draw together common themes of these fascinating, yet devastating diseases. With a total of eight invited speakers, before tea and viewing posters, the first session, was devoted to clinical and parasitological aspects while more snail-related aspects were aired during the second session. Providing a suitable platform for discussion and debate, the meeting aimed to attract further focus upon medical malacology and an opportunity to acknowledge the significant contributions to this field by the late Drs David Brown, NHM and Georg Mandahl-Barth, DBL.
The first of the afternoon talks took a clinical tour through the commoner snail-borne diseases seen at The Hospital for Tropical Diseases (HTD), London. Prof. Peter Chiodini (pete...@uclh.org) showed that each year typically 500 in-patients, with a further 6, 500 out-patients, were seen and screened for parasitic and infectious diseases at HTD. Infections could have been contracted in any part of the globe and as a full and detailed diagnostic service is available at HTD, this patient database often provides an important window into many diseases throughout the world. Infections with the trematode worms Clonorchis (intestinal fluke), Fasciola (liver fluke) and Paragonimus (lung fluke) can be often seen in refugees, immigrants and tourists requiring medical attention within the UK but the majority of snail-borne infections are, however, attributable to Schistosoma (blood fluke) with 200 cases per annum of either urinary or intestinal schistosomiasis.
The infection processes of these snail-borne trematodes can be broadly divided into oral and(or) trans-dermal routes of the worms’ larval stages which have been previously released from infected (semi)aquatic snails. During development within the human body, clinical symptoms include urticaria and fevers. After maturation and, depending upon the species of infection, the resultant adult worms reside within the blood vasculature system or internal body cavities of the human host but unlike other parasitic infections, the worms do not directly replicate inside the body but rather produce copious amounts of eggs. It is these eggs which, depending upon the species concerned, may be voided to the environment via sputum, urine or faeces, facilitating the lifecycles of the parasites. Those eggs that fail to exit the body, often become trapped in host tissues and organs, and ultimately trigger the immuno-pathology associated with disease. For example, liver and(or) spleen enlargement can be often seen with Schistosoma mansoni infections while lesions within the uro-genital system are typical of S. haematobium infections. Typically sputum, urine and faecal samples are inspected for parasitological diagnosis using microscopy. However, making a clear and firm diagnosis can sometimes be difficult if eggs are not apparent in the specimen. In such instances a combination of clinical acumen, serology and antigen detection methods may be required although treatment of infections are relatively straightforward. In the vast majority of cases, oral treatment with anthelmintics such as praziquantel (PZQ) is administered on an out-patient basis unless, however, central nervous system complications are known where co-administration of corticosteroids may be necessary under hospital supervision. While PZQ is cheap and effective, Prof. Chiodini expressed his concerns that as no other anthelmintic drugs alternatives were presently available, should drug resistance ever occur, this could dramatically change future patient prognosis which is presently very good.
Oral praziquantel, a cheap effective treatment for schistomiasis (courtesy of SCI)
In stark contrast to the very good clinical prognosis of schistosome-infected cases in the UK, in regions of the world where schistosomiasis is endemic and access to PZQ is severely limited e.g. sub-Saharan Africa, patient prognosis is very poor. Some 200 million people are presently infected with schistosomes and the global disease burden attributable to schistosomiasis, especially within school age children is alarming. Prof. Alan Fenwick (a.fe...@imperial.ac.uk) clearly drew attention to recently revised estimates of the mortality associated with urinary and intestinal schistosomiasis of 150K and 130K per annum respectively. In fact for an infected child in Africa the picture is particularly bleak as the disease is known to play a significant role in enhancing the vicious circle of poverty by maintaining malnutrition & anemia, growth retardation, cognitive impairment and increased susceptibility to other infections. To break out of this vicious circle it is necessary to provide regular anthelmintic treatment and today, with the recent dramatic decline in the price of PZQ, the cost of drug needed for treatment of each child can be as little as US$ 0.07. Indeed the World Health Assembly and Global Millenium Development Goals have very strongly advocated mass use of PZQ in all countries of the world where schistosomiasis is endemic.
Cheap drugs alone are not sufficient to get national de-worming treatment campaigns moving and Prof. Fenwick highlighted the recent exciting progress of the Schistosomiasis Control Initiative (SCI) within Africa (see www.schisto.org). The SCI was initially funded with a start-up grant of US$ 30 million from the Bill & Melinda Gates Foundation to encourage several sub-Saharan countries to implement their nationwide de-worming programmes by providing both financial and technical assistance. This has directly resulted in over 3 million children in Niger, Burkina Faso, Mali, Uganda, Tanzania and Zambia having had a least one round of annual de-worming treatment. As the control programmes expand and annual retreatments are given out, the total number of children benefiting from continuing access to the drug will continue to increase. To better plan for sustainability, thinking beyond de-worming is necessary for improving the health of the world’s poorest people. To streamline the costs of PZQ delivery, attempts are being made to provide an essential package of drugs for control of trachoma, lymphatic filariasis, and intestinal worms and for the extended programme of vaccinations (measles and polio) as well as increased use of nutritional supplements such as vitamin A.
Still with increasing drug usage and higher treatment coverage, the potential threat of evolution of drug resistance to schistosomiasis remains. Drs Juerg Utzinger & Jennifer Keiser discussed the search for novel treatment options for schistosomiasis as well as for other trematode infections, the drug of first choice for the latter being triclabendazole. Both schistosomiasis and food borne trematodiasis will become ever increasingly important in Asia, in particular China, as the future expansion of irrigated areas continues and as the increase in aquaculture creates further conditions favourable for disease transmission. It is expected that some several tens of millions of people will become infected over the next decade. With this in mind there is a very clear remit for drug research, planning for these future needs. One way forward is in the use of existing plant Artemethers and chemical synthetics, which are very active anti-malarial compounds, in the newer context of anthelmintics. Should PZQ ever become ineffective, research has shown that Artemether holds much promise as a future alternative treatment for trematodiasis.
After breaking for tea and viewings selection of posters, Dr David Rollinson (d.ro...@nhm.ac.uk) showed the multi-disciplinary nature of contemporary medical malacology research and how molecular DNA methods have been providing new insight into old problems. For example, development of a precise taxonomy of Bulinus and Biomphalaria has been previously problematic as there are very few amenable anatomical characters for inspection and shell morphology is notoriously misleading. As a consequence the understanding of the phylogeny and evolution of these species has been limited, although demonstrating the roles of such nominal species in the transmission of Schistosoma spp. Detailed molecular investigation in Zanzibar and Senegal have revealed the importance of the snail in determining the epidemiology of the disease. On Zanzibar, the geographic distribution of urinary schistosomiasis in man is highly correlated with the distribution of populations of Bulinus globosus, and Bulinus nasutus is refractory to infection. This latter finding could find important application in biological control of schistosome infections in the environment through manipulation and displacement of B.globosus/nasutus populations. Similarly the low genetic diversity and high compatibility of Biomphalaria pfeifferi in Senegal has no doubt assisted in the local epidemic of schistosomiasis around Richard Toll.
Genomic-wide approaches using DNA chip (microarrays) methodologies are starting to grapple with the molecular determinants of snail-schistosome compatability by looking at the expression of genes within the snail following penetration of miracidia. Using selected breeding lines of Biomphalaria glabrata that are resistant or susceptible to infection, several novel genetic determinants have been isolated following their up- or down-regulation expression patterns. Dr Rollinson drew attention to a possible drawback, however, that with many of these novel genetic targets, the molecular functioning remains difficult to identify precisely using GenBank sequence homology searching. In contrast, to molecular research on insect vectors of disease, where for example there are many mosquito DNA accessions, molluscan data is presently under represented and there is room for improvement. Similarly, integration of laboratory and field studies is required to understand the interactions between snail and parasite populations and it is necessary to use this knowledge to bolster interventions based upon chemotherapy as well as to explore novel methods for improving schistosomiasis control in the environment.
Past experiences have shown that populations of intermediate snail hosts have often proven rather difficult to control. As snails have successfully colonised many areas of Africa and have evolved to meet the needs of these rather ephemeral habitats where population crash and boom is the norm, actions by man are often circumvented. Dr Bertrand Sellin (Bert...@wanadoo.fr) showed that their general adaptability and high reproductive rates have allowed Bulinus and Biomphalaria to endure within many varied environments as well as withstand chemical methods of snail control with aquatic molluscicides. Despite these frustrations field studies of molluscs remain an essential part of a multidisciplinary approach to control and to better understand the complex epidemiology of these diseases. Detailed documentation of the snail population dynamics provides important information for optimal timing of chemotherapy as well as better guiding water resource development and management. For example, such results can help to motivate local communities in showing the success of their attempts to clean canals, keeping snail populations at bay, and therefore minimising the opportunity for schistosome transmission. By reducing the opportunity and rate of reinfections, such actions help to build towards more sustainable control by maximising the benefit of chemotherapy.
Molecular approaches have also shed light on the epidemiology of Asian schistosomiasis, in particular Schistosoma japonicum in China and the Philippines. In contrast to African schistosomes, this asian schistosome utilizes the amphibious snail Oncomelania hupensis (within which molecular DNA work has revealed possible cryptic species) and uses a broader definitive host range of cattles, rodents, pigs and dogs as well as man. Dr Joanne Webster (Joan...@imperial.ac.uk) reviewed the progress made using microsatellite DNA markers to better describe the distribution of schistosome communities within both molluscan and mammalian hosts. Using PCR approaches it is possible to inspect variation of schistosome larval stages and better monitor any genetic heterogeneity. Genetic variation is apparent and as a direct consequence, it appears that the same strains of S. japonicum co-circulate within humans and cattle but remain separate to those within domestic animals, yet all schistosomes use the same species of snail. This raises interesting spatial evolutionary questions regarding potential for co-evolution and determinant of the temporal patterns of infection within the snail.
Shells typical of the snail species found in Lake Victoria (coutesy of Prof. Thomas Kristensen)
The importance of general levels of aquatic snail biodiversity was highlighted by Dr Thomas Kristensen (tkkr...@dblnet.dk). For example owing to their complex lifecycles, the geographic distribution of several snail borne diseases is mainly constrained by the presence of particular species of freshwater gastropod within which infections can successfully develop. Schistosomiasis is perhaps the best known, and in examples taken from Tanzania, Zimbabwe, Ghana and Uganda clear patterns between snails and schistosome can be seen. As often only a single snail species acts as a local intermediate host, it is important to identify snail populations precisely, differentiating between species that are intermediate host species and those that are not. On the other hand the parasite is often less discerning and may penetrate non-host snails and in so doing die. Indeed the presence and diversity of non-host snail species can curtail parasite transmission by blocking the development of larval stages of the parasite. At the same time changes in the environment associated with man’s activities can greatly influence the diversity and density of freshwater gastropods which may favour disease transmission. Indeed such changes have been seen after creation of water impoundment schemes (e.g. Ghana and Egypt) or as consequences of human pollution and over-fishing (e.g. Malawi and Kenya). The changes may manifest themselves rapidly with outbreaks of snail-borne diseases over a short time scale or can be more gradual and subtle where in the patterns of the parasitic faunae alter for example where S. haematobium is replaced by S. mansoni or vice versa.
After giving thanks to the speakers and to The Linnean Society for generously providing the hosting venue, Dr Russell Stothard invited Dr Vaughan Southgate (vrs...@nhm.ac.uk) to review the afternoon’s findings and guide an open questioning session from the floor. Great progress and in-roads have been made into combating morbidity control of snail-borne diseases with PZQ. Such treatment campaigns are having tangible impacts upon improving the health of children in the developing world, especially where previous health services have failed to provide access to anthelmintics. On the other hand, growing concerns are now being raised, and faced, when issues of the longer-term sustainability of chemotherapy-based programmes are discussed.
Piggy-backing de-worming drugs with other common tropical disease medicines to form an essential drug package is certainly the way forward. As with any drug, however, control focused upon one drug alone will eventually have a finite period of efficacy as the potential threat of evolution of drug resistance is realised. In fact, drug resistance is being taken very seriously and a concerted action group exists to monitor the tolerance and susceptibility of schistosomes to praziquantel. So far there is no clear evidence to suggest any erosion of drug efficacy but clearly this situation needs to be continuously monitored. There are strong ethical arguments too for maintaining drug delivery even if PZQ resistance was detected. For example, while the drug still exhibits some benefit in terms of reduction of suffering then why should such medicines be restricted in their use within the poorest communities who live in the greatest need of treatment? As with any other ‘vector-borne’ disease, snail-borne diseases are no exception; medical malacology is an essential component within disease surveillance. Are snail-borne diseases still a threat to global health? Simply put, as there are still hundred of millions of peoples on the globe living in impoverished conditions of poor sanitation and water-hygiene and in close proximity to susceptible snails, the future burden of snail-borne disease will still be devastating.
The meeting greatly benefited from the kind hospitality of staff of the Linnean Society in particular Mr Adrian Thomas. Financial support from the SCI, Imperial College was gratefully received to meet the travel costs of Drs Utzinger and Keiser.
Dr. J. Russell Stothard
Wolfson Wellcome Biomedical Laboratories
Biomedical Parasitology, Department of Zoology
Natural History Museum, London SW7 5BD