Intestinal giardiasis. Mini-review

Giardia intestinalis is a common parasite in our country and the rest of the world and is responsible for several clinical disturbances that include dysentery type diarrheas, recurrent abdominal pain, duodenitis, jejunitis, cholecystitis and in some cases toxemias and convulsions. In this paper we review recent concepts of intestinal giardiasis, considering the basic aspects of the biology and physiology of Giardia intestinalis, its morphology and its relationship the parasite pathogenicity. We detail the physiopathological mechanisms responsible for the different clinic manifestations of giardiasis, the specific laboratory and endoscopic methods of diagnosis and the most recent advances in the treatment and prophylaxis of this disease.     

Quantitative histology in giardiasis.

The Weibel graticule was used to assess quantitatively histological changes in proximal jejunal mucosal biopsies from patients with Giardia lamblia infections. Most had malabsorption. A group of patients who had mild abdominal symptoms but no intestinal infection and normal absorption were the controls. There were significant differences in mean surface area (SA) measurements between patients with giardiasis and severe malabsorption and controls (P less than 0.001) and infected patients with normal absorption (P less than 0.05). SA measurements correlated significantly with D-xylose excretion results (r = 0.55; P less than 0.01) and daily facal fat output (r = -0.61; P less than 0.001). Significant correlations between duration of symptoms and SA measurements (r = 0.43; P less than 0.05) and D-xylose excretion (r = 0.43; P less than 0.05) in giardiasis suggest that histological and functional impairment are maximal soon after infection and resolve in time. Treatment with metronidazole or mepacrine was associated with a significant increase in SA (P less than 0.05) in patients with severe malabsorption but there was little change in SA in a similar group of patients who received tetracycline. The Weibel graticule was found to be useful in assessing the severity of histological changes and in following changes after treatment.     

Chronic giardiasis of the stomach.

Two cases of chronic giardiasis of the stomach diagnosed from gastric mucosal biopsy specimens are reported. The first case was associated with an acute-on-chronic gastritis and Helicobacter-like organisms, and the second with an adenocarcinoma of the stomach. In both cases the trophozoites had been missed in earlier biopsy specimens. As far as is known this is the first report of giardiasis of the stomach.     

Antibodies to cysts of Giardia lamblia in primary giardiasis and in the absence of giardiasis.

The significance of serum antibodies binding to cysts of Giardia lamblia was evaluated by indirect immunofluorescence. Titers of 10 or higher were found in 85.6% of adults, who had probably never had giardiasis. Titers in 118 adults (geometric mean, 29.9) were higher than in 35 children (16.4), and titers in women (42.3) were higher than in men (20.0). Titers in 150 patients with primary giardiasis (80.4) were higher than in control adults, but overlapping precluded serological diagnosis. Titers increased with the duration of infection. Female patients had higher titers (100.5) than did males (66.1), but men who had been infected longer than 45 days had high titers (132). Titers in second serum samples taken from 26 patients 2 weeks to 3 months after successful nitroimidazole treatment (58.1) were lower than before treatment (151.7) but higher than in 118 controls. We conclude that most people have antibodies which cross-react with G. lamblia but which are induced by other immunogens and that primary giardiasis induces protracted systemic antibody responses.     

Immunopathology of giardiasis

Conclusions G. lamblia continues to be the most common human intestinal protozoan parasite worldwide and still poses a major health problem to infants and young children particularly those in the developing world, to travellers in endemic areas, to immunodeficient individuals and communities exposed to waterborne outbreaks. Despite the availability of effective anti-giardial drugs, it is unlikely that these will eradicate the parasite from the environment particularly as there is increasing evidence that there are domestic and wild animal reservoirs of human infection and that giardiasis is likely to be a zoonosis. Understanding the interaction between Giardia and the host immune system may have important implications not only for the biological control of this parasite in the environment but for improving our understanding of the mechanism(s) by which it causes intestinal disease. Despite the fact that Giardia is essentially a luminal pathogen in the gut it does evoke both systemic and local immune responses. Current evidence emphasises the importance of secretory antibody for clearance of the pathogen, although other cell-mediated effector mechanisms are also likely to be involved. The relationship between serum and secretory antibody responses is not clear, particularly as to whether the presence of anti-Giardia antibodies in serum is in any way indicative of the development of protective immunity. The possibility that cell-mediated immune responses in the mucosa could account for the structural and functional abnormalities sometimes observed in human and experimental giardiasis in animals is an intriguing possibility and awaits further experimental verification. The apparent delay in the development of protective immunity despite continuing exposure to the parasite represents a major challenge for clinicians and biologists. It may relate to there being many antigenically diverse strains of the parasite, possibly due to the ability of a single strain to vary its surface antigens. Passage of the parasite through other mammalian hosts and exposure to bacterial endosymbionts and RNA viruses may also result in phenotypic changes sufficient to nullify a previous immune response to the parasite. These challenging questions await further investigation.     

Treatment of giardiasis

Giardia lamblia is both the most common intestinal parasite in the United States and a frequent cause of diarrheal illness throughout the world. In spite of its recognition as an important human pathogen, there have been relatively few agents used in therapy. This paper discusses each class of drugs used in treatment, along with their mechanism of action, in vitro and clinical efficacy, and side effects and contraindications. Recommendations are made for the preferred treatment in different clinical situations. The greatest clinical experience is with the nitroimidazole drugs, i.e., metronidazole, tinidazole, and ornidazole, which are highly effective. A 5- to 7-day course of metronidazole can be expected to cure over 90% of individuals, and a single dose of tinidazole or ornidazole will cure a similar number. Quinacrine, which is no longer produced in the United States, has excellent efficacy but may be poorly tolerated, especially in children. Furazolidone is an effective alternative but must be administered four times a day for 7 to 10 days. Paromomycin may be used during early pregnancy, because it is not systematically absorbed, but it is not always effective. Patients who have resistant infection can usually be cured by a prolonged course of treatment with a combination of a nitroimidazole with quinacrine.     

Epidemiology of giardiasis

Prevalence analysis in the Gard; fluctuations according to seasons, age and sex. Statement a excystation method after passage in a induction solution; observations and excystation rate. Cysts resistance study in exterior middle at various temperature: at dry from -5 degrees C to 40 degrees C, in fresh water from -5 degrees C to 20 degrees C and in sea water at 10 degrees and 20 degrees C. Epidemiologic consequences.     

Molecular epidemiology of giardiasis

Giardia duodenalis is a widespread parasite of mammalian species, including humans. Due to its invariant morphology, investigation on aspects such as host specificity and transmission patterns requires a direct genetic characterization of cysts/trophozoites from host samples. A number of molecular assays have been developed to help unravel the complex epidemiology of this infection. A coherent picture has emerged from those studies, indicating the existence of seven genetic groups (or assemblages), two of which (A and B) are found in both humans and animals, whereas the remaining five (C-G) are host-specific. Sequence-based surveys have identified a number of genotypes within assemblages A and B in animal species, some of which may have zoonotic potential. Recently, however, molecular approaches have been complicated by the recognition of intra-isolate sequence heterogeneity (i.e., "mixed templates", that affects identification of subtypes within each assemblage), and by the unreliable assignment of isolates to G. duodenalis assemblages generated by different genetic markers. This raises concerns about previous interpretation of genotyping data, especially when single genetic markers have been used. The mechanisms that may be responsible for these findings, including allelic sequence heterozygosity and meiotic recombination, are discussed.     

Chronic giardiasis in B-cell-deficient mice expressing the xid gene.

The role of antibody in immunity to Giardia muris infection was investigated by studying B-cell-deficient CBA/N mice expressing the xid gene. After gastric administration of infective G. muris cysts, CBA/N male and female mice developed prolonged G. muris infection, whereas BALB/c mice eliminated their infection in 6 to 8 weeks. Male F1 progeny obtained from matings between female CBA/N mice and male BALB/c mice expressed the xid gene and developed prolonged infections. In contrast, all other F1 progeny of CBA/N and BALB/c matings, which did express the xid gene, eliminated G. muris. The link between the xid gene and prolonged infection was confirmed by studies of C57BL/6 mice congenic for the xid gene. When compared with BALB/c or F1 mice, CBA/N mice produced large quantities of immunoglobulin A (IgA) anti-G. muris antibody in serum and gut secretions during prolonged infection. Serum IgG anti-G. muris antibody levels were reduced in CBA/N and F1 male mice that expressed the xid gene. The inability of xid mice to eliminate G. muris is consistent with the importance of antibody in the development of immunity to G. muris. We hypothesize that mice bearing the xid gene fail to produce IgA antibody of appropriate specificity to an antigen or antigens whose recognition by antibody is critical for successful elimination of the parasite.     

Serum IgE levels in giardiasis

Raised levels of serum immunoglobulin E are found in many parasitic diseases. In order to determine the influence of Giardia lamblia on IgE levels of clinically symptomatic patients, a controlled study was performed. There was no difference between the serum IgE values from Brazilian patients with giardiasis and those from normal Brazilian controls, although in both groups there were many individuals with values higher than the normal range reported from the northern hemisphere.     

Serum antibodies and jejunal histology in giardiasis associated with malabsorption.

An immunofluorescent test, using Giardia lamblia cysts as antigen, gave positive results in 32/36 cases of giardiasis with malabsorption, 0/2 cases of giardiasis without malabsorption, and 0/17 control patients without giardiasis or malabsorption. The test was positive in 10/34 patients with malabsorption in whom G. lamblia could not be detected by stool examination or biopsy; some of these cases were presumed to be cryptic giardiasis. There was a crude correlation between antibody titre and the severity of the histological lesion in the jejunum. The finding of a reliable source of antigen remains a problem.     

Electron microscopy in the diagnosis of giardiasis

Biopsy specimens of intestinal mucosa from two patients with malabsorption syndrome were examined with routine light and electron microscopy. Both showed intact intestinal mucosa, but by electron microscopy, the presence of Giardia lamblia in the intervillar spaces was identified. Electron microscopy is useful for the identification of this parasite, since the stool examinations in up to 50% may be negative. The parasites appear in light microscopy as cellular debris and can be easily overlooked, while by electron microscopy the typical morphologic features of the parasite are diagnostic.     

A family cluster of giardiasis with variable treatment responses: refractory giardiasis in a family after a trip to India

Persistence of giardiasis after some of the recommended drugs is occurring with increasing frequency. We describe the follow-up of four members of a family with giardiasis through microscopic observation, immunochromatography and PCRs of tpi and β-giardin genes. Three patients did not respond to tinidazole but they were cured after quinacrine. However, PCR became negative at 2 months after negativization of stools in two patients and after 1 year in one patient. In all cases Giardia assemblage B was characterized with high homology between all isolates. Further studies are needed to determine the value of PCR in the diagnosis of Giardia infections.     

Immune response to Giardia lamblia in a water-borne outbreak of giardiasis in Sweden.

In one of the largest outbreaks of waterborne giardiasis reported from Europe, more than 3000 persons were exposed to contaminated water and over 1400 cases of giardiasis were diagnosed by microscopy. The outbreak resulted from an overflow of sewage water into the drinking water system of a Swedish ski resort. The period of contamination was about 1 week. Sweden is a non-endemic area for Giardia lamblia infection and, for most individuals affected, this was their first contact with the parasite. Few other enteropathogens were isolated from the patients involved. Therefore, an immune response to Giardia was unlikely to be biased by other concomitant infections. Serum samples from 352 exposed persons were collected and analysed for specific IgG and IgA antibodies to G. lamblia by indirect immunofluorescence and the results were related to the microscopic examination of faeces and the occurrence of diarrhoea. As controls, sera from 428 healthy persons were analysed at the same time by identical methods. IgG or IgA antibodies, or both, were found in 68% of patients whose diagnosis was made by microscopy, and in 22% of exposed by microscopically Giardia-negative persons, but in only 10% of healthy controls. The findings show that patients reported as negative for parasites might be infected. The time between infection and blood sampling influenced the result of the antibody test. The results suggest that stool examination should be the primary means of diagnosis of G. lamblia infection and that serological analysis performed at least 3 weeks after infection could contribute to diagnosis in a non-endemic region, when giardiasis is suspected but the parasite has not been detected.