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      Human Intestinal Parasites

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          Abstract

          Parasitic infections, caused by intestinal helminths and protozoan parasites, are among the most prevalent infections in humans in developing countries. In developed countries, protozoan parasites more commonly cause gastrointestinal infections compared to helminths. Intestinal parasites cause a significant morbidity and mortality in endemic countries. Helminths are worms with many cells. Nematodes (roundworms), cestodes (tapeworms), and trematodes (flatworms) are among the most common helminths that inhabit the human gut. Usually, helminths cannot multiply in the human body. Protozoan parasites that have only one cell can multiply inside the human body. There are four species of intestinal helminthic parasites, also known as geohelminths and soil-transmitted helminths: Ascaris lumbricoides (roundworm), Trichiuris trichiuria (whipworm), Ancylostoma duodenale, and Necator americanicus (hookworms). These infections are most prevalent in tropical and subtropical regions of the developing world where adequate water and sanitation facilities are lacking (1,2). Recent estimates suggest that A. lumbricoides can infect over a billion, T. trichiura 795 million, and hookworms 740 million people (3). Other species of intestinal helminths are not widely prevalent. Intestinal helminths rarely cause death. Instead, the burden of disease is related to less mortality than to the chronic and insidious effects on health and nutritional status of the host (4,5). In addition to their health effects, intestinal helminth infections also impair physical and mental growth of children, thwart educational achievement, and hinder economic development (6,7). The most common intestinal protozoan parasites are: Giardia intestinalis, Entamoeba histolytica, Cyclospora cayetanenensis, and Cryptosporidium spp. The diseases caused by these intestinal protozoan parasites are known as giardiasis, amoebiasis, cyclosporiasis, and cryptosporidiosis respectively, and they are associated with diarrhoea (8). G. intestinalis is the most prevalent parasitic cause of diarrhoea in the developed world, and this infection is also very common in developing countries. Amoebiasis is the third leading cause of death from parasitic diseases worldwide, with its greatest impact on the people of developing countries. The World Health Organization (WHO) estimates that approximately 50 million people worldwide suffer from invasive amoebic infection each year, resulting in 40-100 thousand deaths annually (9,10). Cryptosporidiosis is becoming most prevalent in both developed and developing countries among patients with AIDS and among children aged less than five years. Several outbreaks of diarrhoeal disease caused by C. cayetanensis have been reported during the last decade (11). Spread of these protozoan parasites in developing countries mostly occurs through faecal contamination as a result of poor sewage and poor quality of water. Food and water-borne outbreaks of these protozoan parasites have occurred, and the infectious cyst form of the parasites is relatively resistant to chlorine (12). Other species of protozoan parasites can also be found in the human gut, but they are not pathogenic, except Microsporidia sp. In an article published in this issue of the Journal, Jacobsen et al. looked at the prevalence of intestinal parasites in young Quichua children in the highland or rural Ecuador (13). They have found a high prevalence of intestinal parasites, especially the intestinal protozoan parasites. They have used the traditional microscopic technique to diagnose intestinal parasitic infections. In total, 203 stool samples were examined from children aged 12-60 months and found that 85.7% of them had at least on parasite. The overall prevalence of intestinal protozoan parasites were: E. histolytica/E. dispar 57.1%, Escherichia coli 34.0%, G. intestinalis 21.1%, C. parvum 8.9%, and C. mesnili 1.7%, while the prevalence of intestinal helminthic parasites in this study were: A. lumbricoides 35.5%, T. trichiura 0.5 %, H. diminuta 1.0%, and S. stercoralis 0.7%. A recent study in Nicaragua in asymptomatic individuals found that 12.1% (58/480) were positive for E. histolytica/E. dispar by microscopy, but E. histolytica and E. disapr were positive by polymerase chain reaction (PCR) only in three and four stool samples respectively among the microscopic positive samples (Unpublished data). This study proves again that the diagnosis of E. histolytica/E. dispar is neither sensitive nor specific when it is done by microscopy. To understand the real prevalence of E. histolytica-associated infection, a molecular method must be used for its diagnosis. Over the last several years, we have seen new approaches to the diagnosis, treatment, and prevention of intestinal protozoan parasites. However, the diagnosis and treatment of intestinal helminth infections have not been changed much, and the traditional microscopic method can be used for their diagnosis. Antigen-detection tests are now commercially available for the diagnosis of all three major intestinal protozoan parasites. Diagnosis of E. histolytica cannot be done any longer by microscopy, since this parasite is morphologically similar to the non-pathogenic parasite E. dispar. E. histolytica-specific antigen-detection test is now commercially available from TechLab, Blacksburg, Virginia, for the detection of E. histolytica antigen in stool specimens (14,15). In several studies, this E. histolytica-specific antigen-detection test has been used for the specific detection of E. histolytica (16,17). These studies have found that this antigen-detection test is sensitive and specific for the detection of E. histolytica. In a study in Bangladesh, E. histolytica-specific antigen-detection test identified E. histolytica in 50 of 1,164 asymptomatic preschool children aged 2-5 years (18). In a study in Nicaragua among patients with diarrhoea, where E. histolytica-specific test has been used, found that the prevalence of E. histolytica was 0.5% (19). In a study conducted in a cohort of Bangladeshi children found that the prevalence of E. histolytica in diarrhoeal stool samples was 8.0% (20). No studies that have been carried till date using E. histolytica-specific diagnostic test reported the prevalence of E. histolytica more than 10%. In addition to the antigen-detection test, several PCR-based tests specific for E. histolytica have been developed and used for specific detection of E. histolytica (21,22). Rapid diagnostic test for the detection of E. histolytica antigen in stool specimens has also been reported (23). Diagnosis of giardiasis is best accomplished by detection of Giardia antigen in stool, since the classic microscopic examination is less sensitive and specific. A recent comparison of nine different antigen-detection tests demonstrated that all had high sensitivity and specificity, except one (24). Giardia-specific antigen-detection tests are now also commercially available from several diagnostic companies, and their performance is quite good, except a few. In addition to antigen-detection tests, PCR-based test for the detection of G. intestinalis has also been reported (25). The population genetics of Giardia are complex. However, a recent genetic linkage study has confirmed the distinct grouping of Giardia in two major types (26). These two main genotypes/assemblages of G. intestinals are commonly known as: assemblage A and assemblage B of G. intestinalis. Differentiation of these two assemblages of G. intestinalis can only be done by PCR-based tests. Findings of the largest case-control study conducted to date on the relationship between genotypes of G. intestinalis and symptoms of patients have been published (27). This study has shown that the Giardia assemblage A infection is associated with diarrhoea. In contrast, Giardia assemblage B infection is significantly associated with asymptomatic Giardia-associated infection, which was found to occur at a significantly higher rate (18.0%) as detected by the antigen-detection test (27). The PCR-based approach allowed resolution of infection to the genotype level and brought some clarity to the findings of asymptomatic giardiasis. Similar large-scale case-control studies need to be carried out in other continents to understand more on the association of Giardia assemblages with diarrhoea/dysentery. Diagnosis of cryptosporidiosis is also best accomplished by detection of Cryptosporidium spp. antigen in stool samples, since classic microscopic examination is less sensitive, and modified acid-fast staining is required. Cryptosporidium spp.-specific antigen-detection test has been used in several studies and has been found to be sensitive and specific compared to classic microscopic examination and PCR-based test (28,29). There are two main species of Cryptosporidium that infect humans: C. hominis (genotype I) and C. parvum (genotype II). The PCR-based test is required for differentiation of these two species of Cryptosporidium spp. (30). Both C. hominis and C. parvum have been found in humans. There are a few other species of Cryptosporidium that also can be found in humans (31–33). Rapid diagnostic tests for the detection of G. lamblia and Cryptosporidium spp. have also been reported (34,35). Multiplex PCR-based test for the detection of E. histolytica, G. intestinalis, and Cryptosporidium spp. has already been reported, and the development of multiplex antigen-detection test for these three common and pathogenic intestinal protozoan parasites is underway at TechLab, Blacksburg, Virginia (36, Herbain J. Personal communication, 2007). These modern antigen-detection tests and PCR-based tests need to be used for understanding the actual prevalence and epidemiology of these protozoan parasites. Soil-transmitted helminth infections are invariably more prevalent in the poorest sections of the populations in endemic areas of developing countries. The goal is to reduce morbidity from soil-transmitted helminth infections to such levels that these infections are no longer of public-health importance. An additional goal is to improve the developmental, functional and intellectual capacity of affected children (37). Highly-effective, safe single-dose drugs, such as albendazole, now available, can be dispensed through healthcare services, school health programmes, and community interventions directed at vulnerable groups (38). As these infections are endemic in poor communities, more permanent control will only be feasible where chemotherapy is supplemented by improved water supplies and sanitation, strengthened by sanitation education. In the long term, this type of permanent transmission control will only be possible with improved living conditions through economic development. Intestinal protozoa multiply rapidly in their hosts, and as there is a lack of effective vaccines, chemotherapy has been the only practised way to treat individuals and reduce transmission. The current treatment modalities for intestinal protozoan parasites include metronidazole, iodoquinol, diloxanide furoate, paromomycin, chloroquine, and trimethoprim-sulphamethoxazole (39). Nitazoxanide, a broad-spectrum anti-parasitic agent, was reported to be better than placebo for the treatment of cryptosporidiosis in a double-blind study performed in Mexico (40). Genomes of these three important protozoan parasites have already been published (41–43), and studies are underway to understand protective immunity to these protozoan parasites to develop vaccines for them.

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          Most cited references43

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          Amoebiasis.

          Amoebiasis is the second leading cause of death from parasitic disease worldwide. The causative protozoan parasite, Entamoeba histolytica, is a potent pathogen. Secreting proteinases that dissolve host tissues, killing host cells on contact, and engulfing red blood cells, E histolytica trophozoites invade the intestinal mucosa, causing amoebic colitis. In some cases amoebas breach the mucosal barrier and travel through the portal circulation to the liver, where they cause abscesses consisting of a few E histolytica trophozoites surrounding dead and dying hepatocytes and liquefied cellular debris. Amoebic liver abscesses grow inexorably and, at one time, were almost always fatal, but now even large abscesses can be cured by one dose of antibiotic. Evidence that what we thought was a single species based on morphology is, in fact, two genetically distinct species--now termed Entamoeba histolytica (the pathogen) and Entamoeba dispar (a commensal)--has turned conventional wisdom about the epidemiology and diagnosis of amoebiasis upside down. New models of disease have linked E histolytica induction of intestinal inflammation and hepatocyte programmed cell death to the pathogenesis of amoebic colitis and amoebic liver abscess.
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            Genomic minimalism in the early diverging intestinal parasite Giardia lamblia.

            The genome of the eukaryotic protist Giardia lamblia, an important human intestinal parasite, is compact in structure and content, contains few introns or mitochondrial relics, and has simplified machinery for DNA replication, transcription, RNA processing, and most metabolic pathways. Protein kinases comprise the single largest protein class and reflect Giardia's requirement for a complex signal transduction network for coordinating differentiation. Lateral gene transfer from bacterial and archaeal donors has shaped Giardia's genome, and previously unknown gene families, for example, cysteine-rich structural proteins, have been discovered. Unexpectedly, the genome shows little evidence of heterozygosity, supporting recent speculations that this organism is sexual. This genome sequence will not only be valuable for investigating the evolution of eukaryotes, but will also be applied to the search for new therapeutics for this parasite.
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              The genome of the protist parasite Entamoeba histolytica.

              Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries. Here we present the genome of E. histolytica, which reveals a variety of metabolic adaptations shared with two other amitochondrial protist pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include reduction or elimination of most mitochondrial metabolic pathways and the use of oxidative stress enzymes generally associated with anaerobic prokaryotes. Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial genes into the E. histolytica genome, the effects of which centre on expanding aspects of E. histolytica's metabolic repertoire. The presence of these genes and the potential for novel metabolic pathways in E. histolytica may allow for the development of new chemotherapeutic agents. The genome encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence. Additional genome features include an abundance of tandemly repeated transfer-RNA-containing arrays, which may have a structural function in the genome. Analysis of the genome provides new insights into the workings and genome evolution of a major human pathogen.
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                Author and article information

                Contributors
                Role: Scientist and Head of Parasitology Laboratory
                Journal
                J Health Popul Nutr
                JHPN
                Journal of Health, Population, and Nutrition
                International Centre for Diarrhoeal Disease Research, Bangladesh
                1606-0997
                December 2007
                : 25
                : 4
                : 387-391
                Affiliations
                Laboratory Sciences Division, ICDDR,B, GPO Box 128, Dhaka 1000, Bangladesh Email: rhaque@ 123456icddrb.org
                Author notes

                Correspondence and reprint requests should be addressed to: Dr. Rashidul Haque, Scientist and Head of Parasitology Laboratory, Laboratory Sciences Division, ICDDR,B, GPO Box 128, Dhaka 1000, Bangladesh, Email: rhaque@ 123456icddrb.org

                Article
                jhpn0025-0387
                2754014
                18402180
                c6da151b-00a1-481d-b185-df7d5524bd65
                © INTERNATIONAL CENTRE FOR DIARRHOEAL DISEASE RESEARCH, BANGLADESH

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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