Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 10, Issue 5, 2010

Infections caused by food-borne parasites continue to be a serious public health problem, especially in the developing world. In the industrial countries, this kind of illnesses are not uncommon in the segment of population who adhere to fad diets containing raw flesh and in cultures where dishes made of raw fish or meat are a long-standing tradition. It is believed that the most effective solution to this problem lies in education of the populace about proper cooking procedures as well as in the improvements of sanitation and food testing technologies in the food industry. Be that as it may, food-borne infections are unlikely to disappear any time soon and effective treatments are absolutely necessary for effective management of the illnesses caused by parasites. The advances in medical science and pharmacology during the past few decades have brought us a variety of effective anti-parasitic drugs that are able to clear a patient of certain types of food-borne parasites almost completely within a few weeks. Nonetheless, many of these drugs have serious side effects and are only effective during one particular stage of the life cycle of a parasite. In some infections, such as angiostrongyliasis, the existing antihelminthic drugs are not effective or only marginally effective. In other words, there is plenty of room for improvement among the currently used antihelminthic treatments and we need new medicines that are safer and more effective. The great progress that has been made recently in the genetics of common parasites and in elucidating the function of various parasitic proteins and other macromolecules has made it possible to identify novel promising therapeutic targets in the parasitic infections of humans. This special issue of Infectious Disorders - Drug Targets is dedicated to the review of recent literature on precisely this topic: new drug targets for the treatment of helminth infections. We have eight interesting and thought-provoking articles, each dealing with a different species of food-borne parasites. These articles provide a state-ofscience review of parasite biology, life cycle, current guidelines for diagnosis and treatment, and, most importantly, future directions in the search for novel modalities for treatment and prevention of a relevant human illness. The readers will enjoy the thoroughness and clarity of presentation of the material. This up-to-date synthesis of research data will no doubt help the scientific community to develop new treatments and preventive interventions, and, ultimately, to reduce the burden of the parasite-related diseases worldwide.

The Taenia saginata taeniasis-cysticercosis complex is a cosmopolitan zoonosis of great medical, veterinary and economic importance where humans play an important role as the carrier of adult stage and cattle as carrier of the larval stage of the parasite. Here we reviewed aspects concerning diagnosis, vaccine development, biological control and treatment of the disease.

Eosinophilic meningitis caused by Angiostrongylus cantonensis is an emerging infectious disease. It is the most common form of human angiostrongyliasis. The diagnosis is made by clinical criteria including the presence of cerebrospinal fluid eosinophils and a history of exposure to A. cantonensis larvae, e.g., from raw freshwater snails or contaminated vegetables. Among various treatment options, corticosteroid is the only effective treatment.

Although giardiasis has been a threat to mankind for thousands of years, this protozoan infection was, until recently, relatively neglected. Giardia duodenalis is recognised as a major cause of parasite-induced diarrhoea in humans and animals, and is currently an important public health problem, placing a heavy burden on both diagnostic and treatment services at health care institutions, mostly in developing countries, but also in highly developed countries. Steady progress in recent years, using a combination of molecular, immunological, and clinical approaches, has substantially increased our understanding of Giardia and important aspects of the clinical manifestations that it causes. The purpose of this review is to provide an overview of the extent of Giardia infection, the implications of water and food in Giardia transmission, new aspects regarding clinical diagnosis and environmental detection, treatment, and some approaches towards prevention and control. A number of future research priorities are also presented.

A. lumbricoides is the largest of the common nematode parasites of man and has been associated with intestinal pathology, respiratory symptoms and malnutrition in children from endemic areas. Current anthelmintic treatments have proven to be safe. However, a reduced efficacy of single dose drugs has been reported. In veterinary practice, anthelmintic drug resistance is an irreversible problem. Thus, research and development of sensitive tools for early detection of drug resistance as well as new anthelmintic approaches are urgently needed. In this review, we summarized data providing information about current drug therapy against A. lumbricoides and other intestinal helminths, new drugs in experimental trials, future drugs perspectives and the identification of immunogenic parasite molecules that may be suitable vaccine targets. In addition to the WHO recommended drugs (albendazole, mebendazole, levamisole, and pyrantel pamoate), new anthelmintic alternatives such as tribendimidine and Nitazoxanide have proved to be safe and effective against A. lumbricoides and other soil-transmitted helminthiases in human trials. Also, some new drugs for veterinary use, monepantel and cyclooctadepsipeptides (e.g., PF1022A), will probably expand future drug spectrum for human treatments. The development of genomic technology has provided a great amount of available nematode DNA sequences, coupled with new gene function data that may lead to the identification of new drug targets through efficient mining of nematode genomic databases. On the other hand, the identification of nematode antigens involved in different parasite vital functions as well as immunomodulatory molecules in animals and humans may contribute to future studies of new therapeutic approaches.

Cyclosporiasis is a protracted, relapsing gastroenteritis and has a short recorded history. Cyclospora cayetanensis is an enigmatic parasite since its discovery highlights the need for isolation of cases of infection that could be part of widespread outbreaks. It is associated with diarrhoea among children in developing countries in the Americas, where C. cayetanensis is endemic; traveller's diarrhoea and/or food and waterborne outbreaks sometimes occur in the developed countries. In SubSaharan Africa and Egypt, cyclosporiasis has been reported to occur in both immunocompromised and immunocompetent patients. Zoonotic species of Cyclospora have also been identified worldwide in primates, indicating likely endemicity of this underreported disease. This can be attributed to the lack of awareness in the public and medical profession concerning the disease, which is, therefore, not routinely tested at the health centres. The correlation between the density of water contamination and the prevalence of cyclosporiasis among the individuals of each area is significant. No doubt, water is the main vehicle of transmission in the present community. Soil contact and poultry are significant risk factors. All literature on C. ayetanensis, cyclosporiasis worldwide, and endemic cyclosporiasis was searched from libraries, colleagues and internet. Although cyclosporiasis is considered an enigma worth unravelling, with many aspects of this disease and its transmission having been uncovered only recently, the situation has been rapidly changing since the disease first came to medical attention in the 1970s.

The nematode Trichinella spiralis and related species are zoonotic food-borne pathogens of humans. The muscle larval stage of this parasite establishes a chronic infection in skeletal muscle cells of humans who acquire trichinellosis. Muscle larvae also reside in skeletal muscles of animals, swine in particular, and other food animals, including game animals. These muscle larvae are the source of zoonotic transmission to humans. Once established, muscle larvae become less susceptible to anthelmintics that are effective against other stages of the parasite. Very little information exists to guide discovery of new drug targets and improved methods of eliminating muscle larvae established in muscle cells of humans or food animals. Here we discuss progress that has been made on sequencing the genome of T. spiralis. This informational resource should prove valuable for dissecting molecular characteristics of this parasite that warrant investigation as targets for chemotherapy. The availability of the T. spiralis genome has made possible the comparison of genomes from nematodes that span the evolutionary extremes of the phylum Nematoda. We describe a pan-phylum comparison of genomes that is underway. This comparative genomics approach is expected to identify molecular characteristics that are conserved among all nematodes, and hence applicable to nematode pathogens throughout the phylum, including species from the genus Trichinella. T. spiralis expression data for muscle larvae has been integrated with genome sequences to identify specific genes and proteins with relevance to control of this stage of the parasite. Examples are discussed in which genomic information may advance understanding of T. spiralis biology and new methods for treating infections by this parasite.

Opisthorchosis is a helminthiasis affecting mainly the hepatobiliary system and pancreas; its most dramatic complication is malignization of the organs infected by the parasites. The causative agents of opisthorchosis are two species of liver flukes, the trematodes belonging to the family Opisthorchiidae—Opisthorchis felineus and O. viverrini. The Chinese liver fluke, Clonorchis sinensis, also member of the family Opisthorchiidae, causes clonorchosis, a disease very close in symptomatology. According to different estimations, up to 40 million people are currently infected with these liver flukes and up to 600- 750 million people in Eurasian countries constitute the risk group. These parasites colonize ever-increasing new areas in Eurasia where this disease has never been previously reported. Opisthorchoses are gradually transforming from a local problem of individual geographic regions to a widespead problem; in particular, O. viverrini is now referred to as “an underestimated parasite.” As we see it, O. felineus has all the reasons to share this status. First and foremost, the observed expansion is likely to be connected with the ever-increasing intensity of traffic flows and migration of the infection carriers between cities, regions, and countries. This review briefs the characteristics of O. felineus and the other liver flukes persisting in various countries of Eurasia, clinical manifestations of opisthorchosis, the drugs for chemotherapy of trematodoses, and the strategy for discovery of new antihelminthic drugs.

The discovery history of opisthorchiid flukes dates back more than 200 years. The life cycle of these liver flukes includes prosobranch snails as the first and a big variety of freshwater fish as the second intermediate hosts. Opisthorchis felineus, O. viverrini and Clonorchis sinensis are species of major medical importance, while sporadic cases of human infection with other representatives of this family are also documented in the literature. There are estimations that 17 million people are infected and more than 350 million people are at risk, mainly in Asian countries. Although opisthorchiid flukes live in the bile ducts of the liver and in the gall bladder, they can affect surrounding liver tissue and even other organs. They are also known to induce the production of autoantibodies as well as allergic reactions. However, the main medical significance is their role in the formation of malignant tumors. Since the clinical symptoms are not specific, a diagnosis must be confirmed by parasitological examination or the detection of antibodies. Apart from coproscopical methods, there are more recent and highly specific assays available, like the detection of coproantigen or the detection of DNA. Praziquantel is the drug of choice for the treatment of opisthorchiidosis. In order to prevent infection, consumption of raw flesh of freshwater fish must be avoided.