Showing papers in "Advances in Parasitology in 1998"
TL;DR: The chapter describes levels of heterozygosity revealed by allozymes and patterns of variation in a variety of different sequence types that are distributed in parasite populations, and the ways these patterns can be used to ask questions about the various aspects of nematode biology and epidemiology.
Abstract: Publisher Summary This chapter describes genetic approaches to answer a variety of questions in the population biology of parasitic helminths. It lays particular emphasis on nematode parasites. The chapter describes levels of heterozygosity revealed by allozymes and patterns of variation in a variety of different sequence types. It illustrates the ways this variation is distributed in parasite populations, and the ways these patterns can be used to ask questions about the various aspects of nematode biology and epidemiology. It also discusses the interspecific level and describes the way genetic approaches have clarified ideas on nematode speciation and revealed a wealth of sibling species. The chapter presents examples of the use of markers for clarifying life cycles and deals with genes responsible for drug resistance. It also discusses other miscellaneous uses of genetic markers. Much of this section is speculative and describes fields in which genetic markers should see a greater usage in the future.
TL;DR: Clinically, microsporidiosis most often presents with diarrhea and weight loss as a result of small intestinal injury and malabsorption, and may provoke symptoms related to their specific localization, but no antiparasitic therapy has documented efficacy in Ent.
Abstract: Microsporidia are ubiquitous in nature. Several clinical syndromes have been associated with microsporidiosis, especially in HIV-infected individuals, and include enteropathy, keratoconjunctivitis, sinusitis, tracheobronchitis, encephalitis, interstitial nephritis, hepatitis, cholecystitis, osteomyelitis, and myositis. Diarrhea and malabsorption are the most common clinical problems. Enterocytozoon bieneusi is the most common microsporidial cause of intestinal disease. A second species, Encephalitozoon intestinalis (originally named Septata intestinalis) is associated with disseminated as well as intestinal disease. Microsporidiosis has been seen worldwide, and is recognized as a frequent enteric infection in patients with AIDS. The pathogenesis of intestinal disease is related to excess death of enterocytes as a result of cellular infection. Clinically, microsporidiosis most often presents with diarrhea and weight loss as a result of small intestinal injury and malabsorption. However, microsporidia have been detected in virtually all organs, and may provoke symptoms related to their specific localization. The diagnosis of microsporidiosis is made histologically, either from tissue biopsies or secretions. While transmission electron microscopy was required for diagnosis in the past, special stains and light microscopy, as well as immunohistochemical and molecular techniques are capable of providing a firm diagnosis. Therapeutic options are limited. Enc. intestinalis responds well to albendazole, while no antiparasitic therapy has documented efficacy in Ent. bieneusi infections.
TL;DR: In this critical review, relatively unexplored details of transmission, the interaction with malnutrition and the development of chronic diarrhea, and the need for effective treatment are highlighted.
Abstract: Cryptosporidiosis is now recognized as one of the most common human enteric infections In this critical review, relatively unexplored details of transmission, the interaction with malnutrition and the development of chronic diarrhea, and the need for effective treatment are highlighted Our inability to detect small numbers of foodborne oocysts limits our understanding of this transmission route, and the possibility of respiratory transmission is yet to be rigorously studied The toll this disease imposes on children, especially the malnourished, has not been fully appreciated Indeed, the dynamics of the progression from acute cryptosporidiosis to chronic diarrhea and death of malnourished children is still enigmatic Our knowledge of the intestinal pathophysiology, while limited, is increasing The lack of effective drug therapy is both remarkable and sobering Overall, these unknown areas demonstrate how little we truly know about this parasite
TL;DR: The broad conclusion is that anticryptosporidial agents will have to enter the parasite via the multiple apical membranes that camouflage the parasite, or via the host cell, possibly transported by vesicles to the feeder organelle membrane, which may have major implications for rational drug discovery and design.
Abstract: The taxonomy of the genus Cryptosporidium remains ambiguous, because the current criteria for speciation are insufficient to validate the 6-8 named species. Cross-transmission experiments have shown varying and conflicting results, and the limited genetic data available do not necessarily support currently proposed species designations. The reasons for this ambiguity lie with the ubiquitous nature of Cryptosporidium, probably infecting all vertebrates and variety of tissues therein, and the absence of reference strains with defined virulence attributes that can be linked to genetic markers for comparative analysis. The inability to classify oocysts or confidently to identify their origin, implicate oocysts from all sources as hazardous to humans. Another major issue is the unusual degree of resistance that Cryptosporidium has shown to antiprotozoan and antimicrobial agents. The intracellular but extracytoplasmic domain the parasite occupies is in itself a significant barrier to drug entry. In support of this we outline how the intracellular niche of this parasite differs from the related Apicomplexans, Plasmodium and Toxoplasma, and delineate why the feeder organelle membrane, rather than, or in addition to, the parasitophorous membrane, is the major portal of nutrient entry for Cryptosporidium. The broad conclusion is that anticryptosporidial agents will have to enter the parasite via the multiple apical membranes that camouflage the parasite, or via the host cell, possibly transported by vesicles to the feeder organelle membrane. This may have major implications for rational drug discovery and design.
TL;DR: Phylogenetic analysis of the rRNA sequence from several of the microsporidia suggests that these organisms were early branches in the eukaryotic evolutionary line, androads have recently been made into the molecular biology of these organisms.
Abstract: The term 'microsporidia' is a nontaxonomic designation which is used to refer to a group of intracellular parasites belonging to the phylum Microspora. These eukaryotic obligate intracellular protozoans have been described infecting every major animal group, especially insects, fish and mammals. They are important agricultural parasites in commercially important insects, fish, laboratory rodents, rabbits, fur-bearing animals, and primates. There is now an increasing recognition of microsporidia as important opportunistic pathogens in persons infected with the human immunodeficiency virus (HIV). Microsporidia possess ribosomes with features resembling prokaryotes. Phylogenetic analysis of the rRNA sequence from several of the microsporidia suggests that these organisms were early branches in the eukaryotic evolutionary line. The data on these molecular phylogenetic relationships are reviewed in this paper. Inroads have recently been made into the molecular biology of these organisms and these data are also presented. Diagnosis of microsporidia infection from stool examination is possible and has replaced biopsy as the initial diagnostic procedure in many laboratories. These staining techniques can be difficult, however, due to the small size of the spores. The specific identification of microsporidian species has classically depended on ultrastructural examination. With the cloning of the rRNA genes from the human pathogenic microsporidia it has been possible to apply polymerase chain reaction (PCR) techniques for the diagnosis of microsporidial infection at the species level. Both staining and PCR techniques for the diagnosis of microsporidia are reviewed.
TL;DR: The morphology, life cycle, taxonomy, and host-parasite relationships of the species of microsporidia that infect mammals are described, which include early eukaryotes, prokaryote-like ribosomes, and mitochondria.
Abstract: Microsporidia (phylum Microspora) are obligate intracellular protozoan parasites that infect a wide range of vertebrate and invertebrate hosts. Over 1000 species have been classified into approximately 100 genera, and at least 13 species have been reported to infect mammals. Phylogenetically, the microsporidia are early eukaryotes because they have a true nucleus, possess prokaryote-like ribosomes, and lack mitochondria. The species that infect mammals are relatively small, measuring 2.0-7.0 microns long and 1.5-5.0 microns wide. The mature organism is the spore, which is enclosed by a chitinous coat, making it relatively resistant to the environment. Infections often occur by fecal-oral or urinary-oral transmission, although vertical transmission is quite common in the carnivores. Host cells become infected through a process of germination in which the spore propels its contents through the everting and unwinding polar filament into the host cell. The polar filament is unique to the microsporidia. With a few exceptions, microsporidiosis is typically chronic and subclinical in immunologically competent hosts. Young carnivores infected with microsporidia, however, develop severe and sometimes lethal renal disease, and immunodeficient laboratory animals (e.g. athymic and SCID mice) develop ascites and die from microsporidiosis. This review describes the morphology, life cycle, taxonomy, and host-parasite relationships of the species of microsporidia that infect mammals.
TL;DR: This chapter provides information and the rationale for work in progress in the laboratory that relates to the development of novel approaches for control of the disease, including the identification of molecular targets of parasite origin for drug design, and studies on the structure-activity relationships of partially effective drugs with a view to synthesize more effective derivatives.
Abstract: Much progress has been achieved in the last decade in terms of development of laboratory techniques, reagents and in vivo models. They have undoubtedly contributed to better and more accurate investigations. Despite a concerted effort by many investigators, however, breakthroughs have been minimal. The development of adequate in vitro and in vivo techniques for drug screening, and the intensified and systematic screening, has so far not resulted in the discovery of an effective therapy. The reason for the failure may well be due to the unique biological niche the parasite occupies (discussed at length in the first chapter in this volume). Its location beneath the cell membrane, but outside the cell cytoplasm, may prove a crucial element that needs to be considered when designing new therapeutic approaches. Laboratory investigations on two drugs currently used against chronic Cryptosporidium parvum in acquired immune deficiency syndrome (AIDS) are discussed. This chapter also provides information and the rationale for work in progress in our laboratory that relates to the development of novel approaches for control of the disease. This includes the identification of molecular targets of parasite origin for drug design, and studies on the structure-activity relationships of partially effective drugs with a view to synthesize more effective derivatives. Other investigations attempt to establish the role of secretory antibody, and the merit of repeated mucosal immunizations as a means of providing protection to individuals with AIDS who are at risk of developing chronic C. parvum infection.
TL;DR: Gaps in understanding of water-borne cryptosporidiosis are considered, new methods under investigation that could improve the ability to monitor water for the presence of this organism, and treatment and control strategies to limit the threat to water supplies are considered.
Abstract: Since the infamous outbreak in Milwaukee, WI, USA, of water-borne cryptosporidiosis affecting over 400,000 people, there have been at least 20 smaller outbreaks associated with this parasite in the UK and North America. These events have led to an explosion of interest in and research on the nature of cryptosporidiosis as a dangerous water-borne pathogen, particularly patients with acquired immune deficiency syndrome (AIDS). In addition, several major environmental laws and proposed regulations specifically address the control of this parasite. The possible ramifications of these laws include billions of dollars of modifications to water-treatment facilities in the USA. Unfortunately, the methods used to gather the information on which these laws are based have serious deficiencies that could lead to gross underestimation of the magnitude of this problem. The present review considers gaps in our understanding of water-borne cryptosporidiosis, new methods under investigation that could improve our ability to monitor water for the presence of this organism, and treatment and control strategies to limit the threat to our water supplies.
TL;DR: This chapter reviews the situation of antimalarial drug resistance as seen from the clinical point of view and examines the major developments made in experimental drug resistance in laboratory models.
Abstract: Publisher Summary This chapter defines drug resistance as “the ability of a parasite to survive in the presence of concentrations of a drug that normally destroy parasites of the same species or prevent their multiplication.” The current widespread use of cultures of Plasmodium falciparum in relatively inert erythrocytes for testing levels of parasite response to antimalarial drugs in vitro has opened the road to the development of lines that can have a very high level of drug resistance—far higher than would ever be encountered in falciparum malaria in humans. In this type of model, relative host drug toxicity can be assessed by parallel exposure of mammalian cells in tissue culture. This chapter reviews the situation of antimalarial drug resistance as seen from the clinical point of view. It then examines the major developments made in experimental drug resistance in laboratory models. It also discusses the relatively small number of novel drugs and drug combinations that have been introduced into the clinic in recent years or that are currently under development.
TL;DR: The further refinement of detection and genetic fingerprinting protocols will provide essential tools for indentifying environmental sources of oocysts and elucidating transmission cycles of C. parvum.
Abstract: Publisher Summary The identification of genetic markers for virulence and drug sensitivity is one of the common goals driving the study of Cryptosporidium parvum heterogeneity. A variety of methods have been applied to the study of genotypic and phenotypic polymorphism in C. parvum . Of particular interest are polymorphisms amenable to typing by polymerase chain reaction (PCR) as C. parvum cannot be expanded in vitro . Fingerprinting of isolates by the restriction of PCR fragments or allele-specific PCR has given promising results. As originally observed by isoenzyme analysis, genetic fingerprinting has confirmed the occurrence in humans of unique C. parvum genotypes that are not found among calf isolates. Although, PCR detection of C. parvum DNA from individual oocysts has been reported, the sensitivity of PCR detection when working with environmental or fecal samples is significantly reduced. Therefore, PCR is currently not used for routine diagnosis or environmental monitoring of C. parvum . The further refinement of the detection and genetic fingerprinting protocols can provide essential tools for indentifying the environmental sources of the oocysts of C. parvum and elucidating transmission cycles.
TL;DR: The view is that nematode parasites are the ancient adversaries of the immune system, which has evolved specific strategies for dealing with them that owe little to other infectious agents, such as bacteria and viruses.
Abstract: Publisher Summary Two emerging concepts in the study of intestinal nematode rejection include the view that there are multiple independent mechanisms of rejection and that the primary rodent species—mice and rats—may differ in their final effector mechanisms against individual parasite species. It is noted that immunoparasitology has gained independence and recognition as it is realized that helminthic infections can help explain the basic immunological paradigm then dominating research endeavor—the T h 1 and T h 2 model of CD4 cell function. This seemed an opportune point at which the strengths and weaknesses of past approaches can be examined to develop new and more direct means of investigating host responsiveness in the future. A key element of this view is that nematode parasites are the ancient adversaries of the immune system, which has evolved specific strategies for dealing with them that owe little to other infectious agents, such as bacteria and viruses. Moreover, there is little novelty in host adaptive mechanisms of defense and these have probably all been defined —antibody and activated cells of several lineages. The novelty is the way they are brought together for different parasitic organisms.
TL;DR: This chapter examines critically the scientific rationale and the evidence for PAI for cryptosporidiosis, including practical considerations and future approaches.
Abstract: Passive antibody immunotherapy (PAI) for cryptosporidiosis is a treatment strategy that has been actively pursued in laboratory studies and early-stage clinical studies for the last decade. Several experimental approaches have been initiated, including use of bovine colostrum and colostral antibodies (hyperimmune and natural), monoclonal antibodies, chicken egg yolk antibodies, and even orally administered human plasma antibodies. Most studies have employed oral administration to treat or prevent this intestinal infection. The interest in this treatment strategy has been sparked by the lack of an effective or approved therapy, increased awareness of the widespread nature of this parasite, epidemiological evidence that humoral immunity plays an important role in host resistance, and several early case reports of antibody therapy in which remarkable resolution of the disease was observed. Most studies using a variety of preparations of antibodies administered to animals and humans have shown some degree of efficacy, though the responses have been, for the most part, partial rather than complete resolution of the disease. This chapter examines critically the scientific rationale and the evidence for PAI for cryptosporidiosis, including practical considerations and future approaches.
TL;DR: This chapter provides an updated and comprehensive review on the main features of cattle schistosomiasis and indicates that suitable drugs are not available for mass treatment in domestic stock and are unlikely to be developed in the near future.
Abstract: Publisher Summary This chapter provides an updated and comprehensive review on the main features of cattle schistosomiasis. The adult worms are obligate parasites of the blood vascular system of vertebrates. They live in the perivesical, nasal or mesenteric, and hepatic veins of the host where they feed on blood and produce nonoperculated eggs with a characteristic terminal or lateral spine. As many as 10 different species of schistosomes have been reported to naturally infect cattle. The geographical distribution of schistosome species infecting cattle is mainly determined by the distribution of their respective intermediate host snails. It is noted that most infections in endemic areas occur at a subclinical level. However, it has been established that high rates of prevalence of subclinical infections cause significant losses due to long-term effects on animal growth and productivity and increased susceptibility to other parasitic or bacterial disease. Despite this, schistosomes of veterinary concern have received relatively little attention. In addition, suitable drugs are not available for mass treatment in domestic stock and are unlikely to be developed in the near future. However, recent progress in identifying potentially protective parasite antigens has opened new perspectives in the control strategy against schistosomiasis.
TL;DR: In this paper, the authors focus on the innate and cell-mediated immune mechanisms associated with resistance to and resolution of a C. parvum infection and discuss the role of interferon-gamma (IFN gamma) in mediating the initial resistance to infection.
Abstract: Cryptosporidium parvum has gained much attention as a major cause of diarrhea in the world. Knowledge of the host immune mechanisms responsible for the clearance of this parasite from the gastrointestinal tract may prove to be vital for successful therapeutic treatment of cryptosporidiosis, particularly in the immunodeficient host. This chapter focuses on the innate and cell-mediated immune mechanisms associated with resistance to and resolution of a C. parvum infection. Much of the work in these areas is still in its infancy. Despite this, general consensus supports a role for interferon-gamma (IFN gamma) in mediating the initial resistance to C. parvum, although the mechanism by which this cytokine imparts resistance is unclear. It is also generally agreed that CD4+ T lymphocytes are required for the resolution of both acute and chronic cryptosporidiosis. However, the effector mechanism is again unclear. Several studies suggest that IFN gamma may also be involved in the resolution of cryptosporidiosis. However, the extent to which this cytokine is involved in the actual resolution of infection has been debated. Less extensive studies investigating the participation of other cells and cytokines in the innate and cell-mediated immune responses to C. parvum are also discussed.
TL;DR: This chapter reviews the existing knowledge of the molecular basis of various host-parasite interactions and of specific molecules that may be involved in them, and identifies areas in which further investigation is necessary.
Abstract: Host-parasite interactions occur at a number of stages during the process of infection with Cryptosporidium. Until recently, very little was known about the molecular basis of these interactions or of specific parasite and host molecules involved in them. Within the past decade significant advances have been made in our understanding of Cryptosporidium host-parasite interactions and in identifying molecules involved in them. However, with most interactions the story is far from complete and a number of gaps remain to be filled. This chapter reviews the existing knowledge of the molecular basis of various host-parasite interactions and of specific molecules that may be involved in them, and identifies areas in which further investigation is necessary. Identification of these molecules and elucidation of molecular mechanisms underlying the host-parasite interaction are of vital importance in developing strategies to combat cryptosporidiosis by targeted chemo- and immunotherapy.
TL;DR: This chapter presents, for western parasitologists and public health workers, a general and concise description of the current state of ascariasis in China based on the most recent information.
Abstract: Publisher Summary Ascariasis is considered to present a significant public health problem to the population in China. Infection with Ascaris lumbricoides exists in all administrative regions and is most prevalent in the south–east of the country. This chapter presents, for western parasitologists and public health workers, a general and concise description of the current state of ascariasis in China based on the most recent information. The chapter discusses following points: (1) the scale of ascariasis in China (2) the distribution of ascariasis geographically and demographically (3) the pattern of ascariasis in China, and (4) whether it follows the pattern demonstrated in other countries. The discussion of these questions is important because it helps to form the basis for placing ascariasis in the order of health priorities for action in the People's Republic of China (P.R.C.). The discussion also raises issues likely to be important for planning, implementing, and sustaining control activities intended to reduce morbidity resulting from ascariasis in China.
TL;DR: The complexity of major surface glycoprotein (MSG) gene expression implies that antigenic polymorphism and variability play an important role in P. carinii pathobiology, and a site-specific endonuclease may be an important target for further investigation into the genetic control of MSG switching.
Abstract: Publisher Summary The clinical importance of Pneumocystis carinii is intensified by the fact that anti- P. carinii drugs have major problems of efficacy and toxicity. With the isolation of nucleic acids from this organism, there have been marked advances in the molecular biology of P. carinii , which led to a resurgence of pathobiological and clinical studies. It is noted that P. carinii is the only fungus that uses a genetic system to switch cell surface determinants. The complexity of major surface glycoprotein (MSG) gene expression implies that antigenic polymorphism and variability play an important role in P. carinii pathobiology. Antigenic variation may contribute to the prevalence of P. carinii pneumonia (PCP) in AIDS patients with a low number of CD4+ T cells, as compared with other microbes. Antigenic variability is used to maintain an opportunistic infection in a single animal host, rather than a series of relapses, because of the moderate alterations in the MSG structures. A site-specific endonuclease(s) may be an important target for further investigation into the genetic control of MSG switching.
TL;DR: This chapter reviews the basic biology of microsporidians that infect mammals, including their unique morphologic characteristics, life cycles, and taxonomy, and discusses the host–parasite relationships of mammalianmicrosporidia, including host specificity, adaptations that promote parasite survival, and host immune response.
Abstract: Publisher Summary The emergence of microsporidia as a clinical problem has coincided with advances in the field of molecular biology, the techniques of which promise greatly enhanced sensitivity and specificity. This chapter reviews the basic biology of microsporidians that infect mammals, including their unique morphologic characteristics, life cycles, and taxonomy. It also discusses the host–parasite relationships of mammalian microsporidia, including host specificity, adaptations that promote parasite survival, and host immune response. This is followed by a discussion of the clinical aspects of microsporidiosis, based mainly upon observations made in patients with AIDS. Particular emphasis is given to intestinal disease, which is the most common problem associated with microsporidiosis. The epidemiology of microsporidia is also discussed in the chapter, including an evaluation of the evidence for and against microsporidia as enteric pathogens. It also discusses the pathogenesis of intestinal and hepatobiliary disease, its clinical pathogical correlations, and its natural course. It presents the currently used diagnostic tests including light and electron microscopic examinations of clinical specimens and discusses the treatment of patients with microsporidiosis, including the studies of specific antiparasitic therapies.