Helmintosis

Manager: Santiago Más-Coma DPUV

In tropical medicine, parasitic diseases are crucial and a cause of underdevelopment in the world. Prominent among these diseases are the helminthiases, due to their frequency, global distribution and devastating repercussions, both on childhood and on impoverished communities in developing countries. In November 2004, the World Health Organisation (WHO) Head Office held the Third Global Meeting of the Partners for Parasite Control (PPC), highlighting the enormous impact of these diseases on human underdevelopment. Furthermore, in addition to the traditional diseases of schistosomiasis, filariasis, ascariasis, trichuriasis and ancylostomiasis-necatoriasis, the decision was taken to include foodborne trematodiases, essentially fascioliasis, cysticercosis and strongyloidiasis on the list of priorities. This unanimous acknowledgement goes to underscore the enormous worldwide problem caused by these helminthiases.

Among the trematodiases, schistosomiasis, with some 250 million persons affected, is currently showing evidence of expanding in certain areas, while resistance to the leading antihelminthic (Praziquantel) is starting to be detected. This disease is followed in importance by fascioliasis, which has around 17 million sufferers infected across Europe, America, Africa and Asia, and is currently in clear process of emerging in many countries and posing a far greater pathological problem than was previously thought. In general, all trematodiases are posing emerging problems, due to the great capacity shown by the gastropod hosts to adapt to climatic and global change, coupled with these molluscs' heightened capacity for spreading geographically.

Cestodes in general, and taeniae in particular, continue to cause serious problems, in terms of public health and economic development, for countries where they are endemic. Apart from the intestinal disorders and malaise caused by adult vermes, the diseases associated with the development of larvae in the intermediate host are those that cause the greatest harm. In this regard, mention might be made of cystic or alveolar hydatidosis and cysticercosis. In view of their clinical and veterinary impact and ensuing financial losses, control methods have been implemented which include improvements in health and hygiene, and changes in behaviour patterns and even in diet. These changes have proved difficult to put in place, with the consequent lack of effectiveness of the programmes designed. Other approaches that would complement the control measures used until now might include the development of vaccines and establishment of new diagnostic methods specific to and sensitive for the taeniasis/cysticercosis duo.

Among the nematodiases, vector-borne filariases continue to pose problems everywhere, which is why they are the focus of attention of major worldwide projects. Among the directly transmitted diseases, ascariasis and trichuriasis rank second, by virtue of the enormous number of sufferers -essentially children- in the world (1,300 and 500 million approximately), and display frequent instances of co-parasitism, not only vis-á-vis each another, but also with fascioliasis. Ancylostomiasis and necatoriasis have an enormous impact on 700 million sufferers, albeit in specific areas in the world. These two are followed by strongyloidiasis, which is noteworthy for the problems it causes among immunodepressed subjects (link with AIDS) and for being endemic in a sizeable area of Spain's Levante region (the Mediterranean coastal belt around the city of Valencia).

Molecular diagnosis of schistosomiasis: Application in the field and follow-up of patients treated with praziquantel.

Head Researcher Teresa Gárate, National Microbiology Centre, Carlos III Institute of Health (ISCIII-B)

Schistosomiasis is a helminthiasis of great public heath importance. It is estimated that there are over 200 million persons infected, with the number of those at risk of acquiring the infection being estimated at 500-600 million. Moroever, it is the second most frequent cause of helminthiasis among newly arrived immigrants in Spain. From a diagnostic standpoint, classic parasitological methods have little sensitivity, principally in the acute phase of the disease. Serology suffers from the drawback of evincing cross-reactivity with other helminthiases. This factor serves as a reminder of an earlier RICET project, aimed at refining a genus-specific PCR using CF1/CR2, and a species-specific S. mansoni using SmF2/SmR, in urine specimens taken from patients with schistosomiasis (Sandoval et al, 2006 Exp Parasitol). Furthermore, this technique has been assessed in an experimental murine model, and proved the most useful of those used (Kato Katz, serology and PCR in stool) (Sandoval et al, 2006 Parasitology). Accordingly, it would be advisable if this new methodology were to be applied on a large scale and its performance as a post-treatment follow-up marker evaluated.

Goals

1.- To study samples of immigrants and travellers from endemic areas for the purpose of accurately defining this technique's sensitivity and specificity in this group.

2.- To apply PCR to urine specimens drawn from persons living in endemic areas, in order to assess the technique's diagnostic performance in such areas. Specimens from endemic areas in Venezuela, Brazil and Guinea will be used.

3.- To assess the usefulness of PCR as a marker after application of drug treatment. To this end, a follow-up will be conducted, covering both the experimental model of infection and patients treated with praziquantel.

Advances in serological diagnosis of strongyloidiasis

Head Researcher Rogelio López-Vélez, Ramón y Cajal Hospital (HRC) 

Strongyloidiasis is a frequent helminthiasis, with the number of persons infested being estimated at anywhere from eighty to one hundred million. Although it has a worldwide distribution and is particularly prevalent in tropical regions, it is also of importance as an endemic parasitic disease (12% prevalence in the Valencian Region). Along with other geohelminths, it is the leading cause of helminthic infection among sub-Saharan immigrants.

Owing to the parasite's autoreplicative cycle in Man, the disease may persist in the body for many years. The severest manifestation of the disease is the hyperinfestation syndrome, which affects parasite-infested individuals subjected to immunodepression, and can prove lethal. Consequently, it is regarded as being one of the main imported parasitoses.

Diagnosis of this entity currently suffers from major limitations, since parasitological diagnosis is somewhat insensitive and serology is still subject to problems of specificity. In addition, these methods do not enable cryptic strongyloidiasis to be detected. In this respect, it would be desirable for diagnostic methods to be developed which enhanced accurate, real detection of this parasitosis.

Goals

1. Diagnosis of strongyloidiasis in immigrants and travellers with suspected parasite infestation (abdominal pathology and/or eosinophilia), for correct treatment and prevention of the hyperinfestation syndrome.

2. To obtain heterologous antigens of different phases of the biological cycle of Strongyloides venezuelensis and characterise immunodominant molecules.

3. To develop an ELISA with S. venezuelensis-specific antigens, in order to enhance diagnostic performance with respect to this helminthiasis versus conventional techniques.

Subprogram: Diagnosis of Helminthiasis and relationship with other pathogens

Manager: Santiago Más-Coma DPUV

Despite their frequency, the importance of co-infections caused by different types of pathogenic organisms (helminths, protozoa, bacteria, viruses) had not been sufficiently highlighted until recently. In mixed infections, the burden of one or both infectious agents may be increased or suppressed, or alternatively, one may be increased and the other suppressed. These interactions are explained in terms of the effects had by the parasites on the immune system, particularly parasite-induced immunodepression, and the effects of cytokines that control the polarisation of the Th1 and Th2 responses of the immune system. The use of models suited to the study of the different facets of concomitant infections is highly advisable. The great impact and ensuing problems of control of multiple helminthic infections in children have been particularly stressed. An excellent model for such studies is fascioliasis, due to the enormous frequency with which it is associated with other concomitant infections, especially in children. These co-infections underlie extremely high childhood mortality (50%) and morbidity.

There is ample evidence of the great epidemiological, clinical, pathological, immunological and diagnostic problem posed in endemic areas, not only in Andean countries (Bolivia, Peru, Ecuador, Colombia and Venezuela) but also in North Africa (Egypt, Morocco) and Asia (Iran, Vietnam, etc.). Of these, the Andean and North African countries are the source of a great proportion of the immigration currently flowing into Spain. Furthermore, fascioliasis is also a problem in south-west Europe, with the highest case rate in France (over 25,000 cases in the period 1950-2000), Portugal (with over 2,000 cases diagnosed near Oporto in 1999) and Spain (with 400 native cases diagnosed in recent years). Added to all the above is the problem of resistance to triclabendazole, the only existing active ingredient for the treatment of humans, which has already appeared in Australia, The Netherlands, Scotland and Ireland and, recently, in Spain.

Goal

The intention is to gain in-depth knowledge of these situations of co-infection, with special stress on molecular epidemiology, pathology, diagnosis, treatment and control. To this end, appropriate studies will be targeted: at endemic areas of endemic countries in America (particularly Bolivia, Peru, Ecuador, Argentina and Venezuela), Africa (Egypt) and Asia (Iran), using the activities pertaining to the WHO worldwide and International Atomic Energy Agency (IAEA) regional initiatives and led without exception by S. Mas-Coma, as the fundamental basis for studying a statistically sufficient number of cases; and at all patients diagnosed in Spanish hospitals that are included in or associated with the Network.

Subprogram: Control

Manager: Teresa Gárate Ormaechea ISCIII-B

Antigens of the secretions and surface (tegument) of helminthic parasites are viewed as key elements in parasitism becoming successfully established. Hence, these have been linked to: (i) molecular events surrounding invasion of the host; (ii) mechanisms that guide the parasite to its final niche; (iii) feeding; (iv) immune response evasion; (v) growth; and, (vi) other processes. In the case of platyhelminths, better knowledge of these components, about which there is limited information, would help in-depth study of the molecular bases of their biology and, in addition, any knowledge so acquired would then be used to improve control of these diseases through the development of vaccines.

Goal

Characterising Schistosoma sp and Taenia saginata/T. solium secretion/tegument antigens by genomics, biocomputer analysis, production in prokaryotic and eukaryotic systems, and performing functional expression in Caenorhabditis elegans and conducting other tests of its possible activity. Further areas targeted for study are the immune response triggered by chosen molecules in established experimentation models and their use as possible candidate vaccines.