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Interleukin (IL) 5 levels and eosinophilia in patients with intestinal parasitic diseases.

AIM: Intestinal parasitic diseases are commonly accompanied with diarrhoeal symptoms and allergic reactions. Eosinophilia occurs as a result of IL-5 synthesized from Th2 cells during allergic reactions. IL-5 acts as a factor activating eosinophils. The aim of this study was to compare the IL-5 cytokine measurements in serum samples and cell cultures. And also to compare eosinophilia observed in helminth infections and protozoon infections accompanied with allergy. METHODS: Twenty-three patients who presented with diarrhoeal symptoms and allergic complaints were tested positive for intestinal parasites, as well as 21 controls with allergic complaints who did not have any intestinal parasites were included in this study. IL-5 production in in vitro cell cultures prepared by using phytohemaglutinin (PHA) to stimulate peripheral blood mononuclear cells (PBMC) obtained from the blood samples taken from these patients were compared with the IL-5 level in serum. Furthermore, the IL-5 production in protozoon and helminth infections was also compared. Absolute eosinophil values in 1 mm(3) of blood were calculated by means of peripheral smear in both groups within the scope of the study. RESULTS: Parasites such as helminth detected in 15 (65.2%) and protozoon in 8 (34.8%) of the patients were included in this study. As regards the values of the sera in both patients with parasite infection and controls, the IL-5 production was found to be higher in the cell culture supernatant (P<0.001 and P<0.05). When the IL-5 level of the patients with helminth parasites was compared with that of those with protozoon, it was determined that the IL-5 level in serum was more significant in the patients with protozoon than in those with helminth (P<0.05). In the study group, the patients were found to have parasites, the percentage of eosinophil was 7.0% compared to 6.5% in the control group. Thus, there was no significant difference between the eosinophil values (P>0.05). CONCLUSION: It was found that IL-5 cytokine levels in serum samples from the patients with helminth and protozoon displayed more measurable values as compared to the IL-5 levels after stimulation with mitogen. It is concluded that IL-5 acts as a triggering factor in the toxiallergic complaints commonly seen in helminth and protozoon infections.

Adult↗

Th2-mediated host protective immunity to intestinal nematode infections.

Despite many years of study, relatively little is known about the effector mechanisms that operate against intestine-dwelling nematodes. Most of the current understanding comes from studies of laboratory model systems in rodents. It is clear that when an intestinal helminth infection takes place the immune system generates a strong Th2-mediated response, which regulates a variety of responses characteristic of helminth infections such as eosinophilia, intestinal mastocytosis and elevated IgE production. The ability to modulate the host's immune response in vivo with cytokine-specific monoclonal antibodies and recombinant cytokines, together with the use of animals with disruption of key genes involved in the immune response, have provided powerful tools with which to dissect the potential effector mechanisms operating. In the absence of a T-cell compartment the host is unable to expel the parasite. If a Th1-dominated response is generated, protective immunity is almost universally compromised. Thus, it it would appear that some aspect of a Th2-mediated response controls effector mechanisms. Although it is clear that for some infections the mast cell appears to be involved in protection, probably through the generation of a non-specific inflammatory response, how these cells become activated remains unclear. Data from infections in transgenic animals suggest that activation is not through the high-affinity receptor for IgE. Such studies also call into doubt the importance of conventional interactions between effector leucocytes and antibody. There is little evidence to support a protective role for eosinophilia in any system. New data also imply that, although interleukin 4 (IL-4) is generally important (and can exert effects independent of an adaptive immune response), it is not always sufficient to mediate protection; other Th2 cytokines (e.g. IL-13) may warrant closer investigation. It is apparent that a number of potential Th2-controlled effector mechanisms (some of which may be particularly important at mucosal surfaces) remain to be explored. Overall, it is likely that worm expulsion is the result of a combination of multiple mechanisms, some of which are more critical to some species of parasite than to others.

Animals↗

Mebendazole and pyrantel pamoate as broad-spectrum anthelmintics.

The efficacy of mebendazole and pyrantel pamoate was studied in two groups of 59 and 58 cases, respectively, of patients with polyparasitosis. Mebendazole had a cure rate of 96%, 82.2%, 71.4% and 66.6% in A. lumbricoides, hookworm, T. trichiura and S. stercoralis, respectively, while the corresponding figures for pyrantel pamoate were 92.6%, 85.7%, 19.4% and 0%. Pyrantel pamoate is considered to have no significant effect on T. trichiura and S. stercoralis. None of the drugs had any effect on T. saginata. Both drugs have been found to be equally effective against enterobiasis by various authors. It is recommended that pyrantel pamoate be the drug of choice in cases of multiple parasitic infections excluding T. trichiura and S. stercoralis whereas those with one or both of these in addition to others should be treated with mebendazole. Mebendazole can be prescribed for patients with clinical evidence of helminthic infections even where stool examination is not possible as it covers almost the whole range of common helminthic infections. The only limitation for poorer patients however is its cost. Pyrantel pamoate has a wider applicability for the poorer patients in spite of the fact that it is ineffective against trichurids and S. stercoralis.

Adolescent↗

Correlations between intestinal parasitosis, physical growth, and psychomotor development among infants and children from rural Nicaragua.

The correlations between malnutrition, parasitosis (especially helminth infections), and child development are complex, and studies of these interrelationships will allow health agencies to maximize screening and intervention strategies for developing countries. We examined these correlations in a cross-sectional program in Carazo State, Nicaragua. Nine hundred sixty-one children in two age strata (ages 0-24 months and ages 2-10 years) from one urban and three rural communities were screened for intestinal parasites (direct smear and ZnSO4 flotation), malnutrition, and developmental delays. Nutritional status was determined as weight-for-age (WFA), weight-for-height (WFH), and height-for-age (HFA). Developmental status (normal, suspect) was determined for the four subtests of the Denver II Screening Test. The prevalence of malnutrition was 14.6% (WFA), 8.4% (WFH), and 36.3% (HFA). Parasitosis was more prevalent in children less than 24 months of age with low HFA, whereas in older children low WFA was more closely associated with parasitic infections. Ascaris and Trichuris were more prevalent in malnourished children. On the Denver II, suspect test results in all four categories (language, social, gross motor, and fine motor) were associated with low WFA, and suspect language tests were associated with both intestinal parasites (P = 0.0003) and Ascaris infection in particular (P = 0.044). Developmental disabilities are a significant and frequently undetected health problem in developing countries, and malnutrition associated with intestinal helminth infections may be an important contributory factor for these disabilities.

Body Height↗

Effect of exposure to malachite green solution on common carp fry with Dactylogyrus vastator (monogenea) infection.

In five experiments, common carp (Cyprinus carpio) fry with Dactylogyrus vastator (Monogenea) infection of different severity, as well as parasite-free fry, were placed into aquaria containing malachite green solution of 0.5-10 mg/l concentration. Most of the fish died within 6 hours. The correlation between the time of death and helminth infection was studied. The experiments demonstrated that in malachite green solution the carp with the heaviest helminth infection died first while the less severely infected specimens survived for the longest time.

Animals↗

Detection of IgG antibodies of Brugian filariasis with crude male and female antigens of Dirofilaria immitis.

Crude antigens from male and female Dirofilaria immitis were used to detect antibody to Brugian filariasis in humans by indirect ELISA. Both antigens were tested with 42 cases of Brugian filariasis, 131 cases of 20 heterologous infections and 35 healthy controls. The results--using male and female antigens--showed sensitivity of 88.1% and 88.1%, and specificities of 64.1% and 51.8%, respectively. Cross-reaction from other helminthic infections using crude male antigen gave false-positives with 48 sera from 13 heterologous diseases at the threshold value of 0.180, while the female antigen gave 63 sera from 15 diseases, at 0.309. Serum antibodies from patients with other helminthic infections--gnathostomiasis, strongyloidiasis, hookworm infections, trichinellosis, capillariasis, angiostrongyliasis, ascariasis, trichuriasis, toxocariasis, neurocysticercosis, cystic echinococcosis, taeniasis and opisthorchiasis--resulted in false-positives with both male and female antigens. One each of sparganosis and paragonimiasis heterotremus sera cross-reacted with only crude female antigen and their OD values were close to the threshold value. Although crude male antigen showed better specificity than crude female antigen, both female and male worms are sources of antigens needed for further purification. This study provides baseline data for further serodiagnosis of Brugian filariasis using dirofilaria antigen.

Animals↗

Atopy and helminths.

In this article, the authors review current and latest evidence linking helminth infections and the development of atopy. Although there is intense ongoing investigation and debate on this issue, the review of experimental, clinical and epidemiological data apparently shows that helminth infections can have beneficial aspects in regard to the pathogenesis of atopy and allergic diseases. Despite the fact that simplistic views are not recommended, it seems that polyclonal IgE production and mainly the stimulation of host immunoregulatory networks leading to synthesis of anti-inflammatory cytokines (IL-10, TGF-beta and others) can provide new insights into how mechanisms that helminths have developed throughout their evolution and that are useful for parasite evasion and persistence, could also be used in humans in order to provide new approaches in atopy prevention.

Animals↗

[The results of a control program carried out on school children for intestinal parasites in Sanliurfa province, Turkey between the years of 2001 and 2005].

This paper presents a school-based deworming program carried out from 2001-2005. It began with baseline studies in 2001 which indicated that intestinal helminth infection was endemic among schoolchildren with a prevalence of 80%in shantytown schools and 53% in apartment district schools. Ascaris lumbricoides was the most frequently detected helminth (45%), followed by Trichuris trichiura (25-30%) and Hymenolepsis nana (10-15%) and Taenia species (5%). Also school children were very much affected by nutritional deficiencies such as prevalence of stunting (24%), underweight (25%) and anemia (45%). The parasite control project was begun in 2002 in which 40.000 school children were treated with a single dose of 500 mg mebendazole. This was followed by delivery of 100.000 doses of mebendazole to the school children during the 2003-2004 school-years. During the 2004-2005 school-years, 120.000 primary schoolchildren, 20.000 high school children, 10.00 rural schoolchildren and 50.000 women and children (1-7 years old) were treated with mebendazole for helminth infections. In October-2005, stool examinations were carried out again in the shantytown and apartment district schools and it was found that the prevalence of infection had declined to 35% in shantytown schools and 6.4% in apartment district schools. The rate of Ascaris lumbricoides infection had fallen to 17%, with the rate of Trichuris trichiura to 1% and that of Taenia species to 0%. In contrast, the rate of Hymenolepsis nana had increased to 21%. These results indicated that parasite control program was successful and should be continued.

Adolescent↗

Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10.

BACKGROUND: Most of the effort directed at understanding the role infections have in preventing allergy has focused on bacteria and viruses and their ability to divert the immune system towards T-helper-1 responses and away from proallergic T-helper-2 responses. However, helminth infections, highly prevalent in large parts of the developing world, where allergy is uncommon, stimulate strong T-helper-2 responses. We investigated the influence of chronic helminth infections on the prevalence of atopy and aimed to understand the relation at a detailed immunological level. METHODS: 520 Gabonese schoolchildren were tested for skin reaction to house-dust mite and other allergens, for Schistosoma haematobium eggs in urine, and for microfilariae in blood samples. Total and mite-specific IgE antibodies were measured. A subsample selected on the basis of their skin test to house-dust mite received detailed immunological investigations. FINDINGS: Children with urinary schistosomiasis had a lower prevalence of a positive skin reaction to house-dust mite than those free of this infection (odds ratio 0.32 [95% CI 0.16-0.63]). The degree of sensitisation to house-dust mite could not explain this difference in skin-prick positivity. Schistosome-antigen-specific concentrations of interleukin-10 were significantly higher in infected children, and higher specific concentrations of this anti-inflammatory cytokine were negatively associated with the outcome of skin-test reactivity to mite (0.53 [0.30-0.96]). No association between polyclonal IgE antibodies and skin-test results was found. INTERPRETATION: The anti-inflammatory cytokine, interleukin-10, induced in chronic schistosomiasis, appears central to suppressing atopy in African children.

Adolescent↗

Gastrointestinal parasite and host interactions.

PURPOSE OF REVIEW: The mechanisms responsible for the Th2-mediated immune response to enteric nematode parasites are of interest for several reasons. First, intestinal parasites continue to be a major worldwide health issue. Second, the low incidence of parasite infection in industrial nations is cited as a factor in the increased prevalence of proinflammatory-based pathologies. Third, a seemingly paradoxical protection against Th2-mediated allergic reactions is afforded by helminth infection. This review focuses on studies that use enteral parasitic infections as a tool to investigate the functional consequences of upregulation of Th2-mediated immunity and that manipulate host-parasite interactions in an effort to identify mechanisms that can be exploited as potential therapeutic targets. RECENT FINDINGS: Enteric helminth infection improved indices of inflammatory bowel disease in humans and murine models and diminished the allergy-induced changes in pulmonary function. There are emerging or enlarged roles for interleukin-10, interleukin-18, interleukin-9, chemokines, activation of nuclear factor-kappabeta, and factors that alter host resistance in the development of host immunity, and for interleukin-13Ralpha2 receptor in downregulating Th2 responses. As part of the growing appreciation for the contribution of nonimmune cells to parasite-induced changes in intestinal function, studies show that Th2 cytokines exert Stat6-dependent effects that promote worm expulsion. SUMMARY: Further insight into the nature of host-parasite interactions, identification of the pathways and critical mediators that contribute to host resistance, identification of the factors that modulate susceptibility to infection, and the impact of enteric parasites on intestinal function hold much promise for development of novel therapeutic interventions.

Journal Article↗

Intestinal parasitism of children and mothers in rural Somalia.

A survey on intestinal parasitism was carried out by microscopic examination of stool specimens from 517 children (0 to 16 years old) or from mothers living in two rural towns in Somalia. Burao represented the hot and dry region in the north and Kismayo the more humid area in the south. The overall prevalances of intestinal parasitism were 48 and 88%, respectively. Protozoal infestation was found in 46% (potentially pathogenic protozoa in 20%) in Burao and 37% (potentially pathogenic protozoa in 17%) in Kismayo. In contrast a major difference between the two towns was observed with helminthic infection. In Burao only 6% of the specimens showed worm eggs or larvae, whereas in Kismayo the prevalence was 84% (P less than 0.001). The difference in helminthic infection rates might be explained by the different climatic factors, different population densities or habits of the people. Among 14 detected parasitoses the following five were found with an overall frequency of 10% or greater: trichuriasis (45%); entamebiasis coli (23%); ascariasis (17%); giardiasis (16%); and ancylostomiasis (15%).

Adolescent↗

A study of the efficacy and safety of albendazole (Zentel) in the treatment of intestinal helmenthiasis in Kenyan children less than 2 years of age.

One hundred children comprising of 57 males and 43 females aged between 8 and 24 months entered the study. 46 children had single and 54 children had multiple helminth infections. All children received albendazole 200 mg (10 ml) suspension as a single dose. Albendazole proved very effective and safe in the treatment of single and multiple helminth infections in children under 2 years of age, achieving cure rates of 100% in both Ascaris lumbricoides and Necator americanus respectively, 83% in Trichuris trichiura and 66% in Hymenolepis nana. Treatment of polyparasitism appears to be of benefit in improving nutritional status using haemoglobin concentrations as an index.

Albendazole↗

Drug treatment of tropical parasitic infections: recent achievements and developments.

Drug development offers potential solutions to a number of tropical health diseases, although the expense of pharmaceutical research and lack of return on investment has limited the production of new agents. The greatest successes have been through the development of single dose therapy and mass treatment control programmes for a number of diseases. We review some of the current treatment regimens for malaria, intestinal helminth infection, onchocerciasis, filariasis and schistosomiasis, and their use in clinical practice. Geographical spread and emergence of drug resistant parasites have hindered the control of malaria, the most important global parasitic infection. Artemisinin compounds have proved effective antimalarial agents producing rapid reduction of parasite load and can be used in combination treatment regimens to combat multidrug resistance. Intestinal helminth infections are widespread, giving rise to nutritional deficiencies and impaired childhood cognitive development. Pregnant women in developing countries are at increased risk of morbidity. Treatment with a single dose benzimidazole such as albendazole or mebendazole has beneficial effects on morbidity and rates of transmission. Diethylcarbamazine has been used in the treatment of onchocerciasis and human filariasis. A complicated escalating dose regimen over several weeks is associated with systemic and allergic reactions and may require corticosteroid cover. Simplified regimens for mass population treatment with ivermectin have proved useful and been used in combination with single dose albendazole and diethylcarbamazine. The African Programme for Onchocerciasis Control in West and Central Africa has been one of the most successful mass control programmes virtually eliminating new infections by a combination of chemotherapy, education and vector control. Schistosomiasis is of increasing importance as a result of the creation of new snail habitats by agricultural and economic development. Praziquantel has become the most widely available and effective chemotherapy for schistosomiasis. There have been a number of reports of persistent schistosome egg shedding after treatment posing concerns about the emergence of drug resistance. Eflornithine has been successfully used in patients with human trypanosomiasis failing melarsoprol therapy however expense and availability have limited its potential. Mass control treatment programmes have targeted schoolchildren, adolescents and pregnant women. The integration of schistosomiasis, onchocerciasis, filariasis and helminth control programmes has been considered as a cost-effective method of delivering treatment. It is likely that future control will be based on this optimisation and integration of existing regimens, rather than the development of new agents.

Anthelmintics↗

Diagnosis of human toxocariasis by antigen capture enzyme linked immunosorbent assay.

AIMS: To evaluate an antigen capture enzyme linked immunosorbent assay (ELISA) which detects a carbohydrate epitope on the excretory-secretory (ES) antigens of Toxocara canis in clinical practice. METHODS: Serum specimens from healthy adults, patients with acute visceral larva migrans, ocular and inactive toxocariasis, and with other helminth infections were examined by two site antigen capture ELISA. RESULTS: Over half of the patients (19/28) with acute toxocariasis had a positive result in contrast to a small proportion of those with inactive disease (1/10) or ocular infection (2/7). False positive reactions, however, were found in 25% of the patients with serologically confirmed schistosomiasis and filariasis. CONCLUSIONS: This assay is useful in confirming the diagnosis of acute visceral larva migrans but could not be used alone in diagnosis because of false positive reactions in patients with other helminth infections.

Adult↗

Use of delipidized antigens of Taenia solium metacestodes in IgG-ELISA for detection of neurocysticercosis.

The development of IgG-ELISA for detecting neurocysticercosis is aimed at the routine laboratory, and requires a particular antigen preparation, an acceptable number of serum samples to be tested (both homologous and heterologous) and patients with a diversity of helminthic infections to rule out cross-reactions. This study characterizes IgG-antibodies from cases of neurocysticercosis by assaying the sera against ether-delipidized antigens (5 microg/ml) prepared from metacestodes of Taenia solium. The test had a sensitivity of 90% and a specificity of 83%. IgG-antibodies from heterologous serum samples elicited a number of false positives (25/147) from six different helminthic infections, ie paragonimiasis, echinococcosis, opisthorchiasis, ascariasis, taeniasis and fascioliasis. In additional tests to detect antibody levels to these stage-related antigens, one of three serum samples from T. solium-infected cases gave negative at OD value of 0.187 while the others yielded 0.472 and 0.576. Conversely, assays of all serum samples from neurocysticercosis cases reacted against antigens from Echinococcus granulosus cystic fluid, Paragonimus heterotremus and Opisthorchis viverrini adult worms. In comparison, the antigens from these three species yielded higher mean OD values when assayed against the corresponding infected serum samples. Furthermore, neurocysticercosis cases yielded OD values that are separate and distinct from those of paragonimiasis cases.

Adult↗

Seasonal variation in the parasite burden and body condition of working donkeys in East Shewa and West Shewa regions of Ethiopia.

A survey of donkeys arriving at markets in three localities in East and West Shewa regions of central Ethiopia was carried out during 2002. Total faecal worm egg counts and body condition scores were measured for a total of 963 donkeys over a 12-month period. Total faecal worm egg counts did not differ significantly between localities but there was significant (p < 0.001) seasonal variation within localities. Levels of helminth infection closely followed rainfall patterns, being lowest (956 eggs per gram of faeces, e.p.g.) at the end of the long dry season (February) and highest (2022 e.p.g.) in the middle of the long wet season (August). Body condition score was associated closely with level of helminth infection (Goodman-Kruskal measure of association 0.60-0.80). Seasonal variation in body condition score reflected the temporal changes in worm burden and the availability of forage. It is suggested that a body condition score of 3 or less could be used as a simple means of identifying donkeys that require therapeutic treatment with anthelmintic. It is further proposed that economically viable strategic control of helminths in donkeys could be achieved by administering a single annual dose of avermectin-based anthelmintic at the start of the long rainy season (May-June). This may allow donkeys to recover body condition when available forage is most abundant and nutritious. It is also recommended that protein-rich feed supplementation be provided during the later part of the dry season (November-January). This may help maintain body condition when forage is scarce and the helminth challenge is at its lowest.

Animal Diseases↗

Human antibody responses against schistosomal antigens. I. Antibodies from patients with Ancylostoma, Ascaris lumbricoides or Schistosoma mansoni infections react with schistosome antigens.

Sera of patients with either hookworm infections or ascariasis, who are from areas nonendemic for Schistosoma mansoni, contain antibody reactivity against extracts of S. mansoni schistosomula. Such patients with hookworm, but not those with Ascaris lumbricoides, also express considerable antibody activity against intact schistosomula and schistosomular membrane preparations. Sera from patients with schistosomiasis mansoni also contain these activities. Because these three helminthic infections often occur in the same areas, and concomitantly in patients, anti-schistosomular reactivity should not be ascribed only to exposure to schistosomes. The demonstration and definition of these surface-specific cross-reactivities point out the problems of serodiagnosis, and the potential of interactive influences in the common occurrence of multiple helminthic infections in humans.

Adolescent↗

Exploiting natural immunity to helminth parasites for the development of veterinary vaccines.

The development of subunit vaccines against most parasitic helminth infections will require a better understanding of the different components of a natural rejection process including (1) recognition of parasite antigens; (2) induction of protective immune response phenotypes; and (3) activation of appropriate immune effector mechanisms. While novel technologies have allowed significant progress to be made in the identification of candidate vaccine antigens, the large scale production of these antigens and their presentation to the host with appropriate adjuvant systems remains a major problem in vaccine research. Identification of the molecular interactions involved in the innate immune response to helminth infections and the application of new genomic and proteomic technologies are likely to lead to major advances in these research fields. Gastrointestinal nematode parasites and liver fluke are the most important helminth parasites of production animals. In recent years, a lot of new knowledge has been gathered on the immunobiology of the host-parasite interactions in these two infection systems, which has allowed new vaccination strategies to be considered. Functional genomic technologies such as gene expression analysis by microarrays, promise to further advance our understanding of the molecular pathways leading to protection against parasite infections. This will not only have implications for vaccine research, but also provide novel targets for drug development and genetic selection.

Animals↗