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Helminth infection protects mice from anaphylaxis via IL-10-producing B cells.

Modulation of the immune system by infection with helminth parasites, including schistosomes, is proposed to reduce the levels of allergic responses in infected individuals. In this study we investigated whether experimental infection with Schistosoma mansoni could alter the susceptibility of mice to an extreme allergic response, anaphylaxis. We formally demonstrate that S. mansoni infection protects mice from an experimental model of systemic fatal anaphylaxis. The worm stage of infection is shown to mediate this protective effect. In vivo depletion studies demonstrated an imperative role for B cells and IL-10 in worm-mediated protection. Furthermore, worm infection of mice increases the frequency of IL-10-producing B cells compared with that in uninfected mice. However, transfer of B cells from worm-infected mice or in vitro worm-modulated B cells to sensitized recipients exacerbated anaphylaxis, which was attributed to the presence of elevated levels of IL-4-producing B cells. Worm-modulated, IL-10-producing B cells from IL-4-deficient, but not IL-5-, IL-9- or IL-13-deficient, mice conferred complete resistance to anaphylaxis when transferred to naive mice. Therefore, we have dissected a novel immunomodulatory mechanism induced by S. mansoni worms that is dependent on an IL-10-producing B cell population that can protect against allergic hypersensitivity. These data support a role for helminth immune modulation in the hygiene hypothesis and further illustrate the delicate balance between parasite induction of protective regulatory (IL-10) responses and detrimental (IL-4) allergic responses.

Adoptive Transfer↗

[Atopic dermatitis: The hygiene hypothesis: Prevention through helminth infections?].

The prevalence of atopic diseases has steadily increased over the past decades. While genetic predisposition remains an important risk factor, environmental conditions appear to be additional relevant trigger factors, leading to the development of the "hygiene hypothesis". Current data indicates that atopic respiratory diseases seem to occur less frequently following helminth infections. This effect may be due to the induction of anti-inflammatory cytokines during the helminth infection. In contrast, atopic dermatitis seems to represent a separate entity influenced by more than "allergic sensitization". Recent data demonstrate a reduced risk for the development of atopic dermatitis following helminth infections. Further studies are needed to more closely examine the connections between helminth infections and this chronic skin disease, as well as to identify immunologic pathways.

Adolescent↗

The prevalence of malnutrition and geo-helminth infections among primary schoolchildren in rural Kelantan.

A cross-sectional study of the nutritional status of schoolchildren aged 7-10 years from the Kuala Betis Resettlement Scheme in Gua Musang, Kelantan was done. A total of 291 schoolchildren were examined but only 183 (62.9%) fecal samples were returned for geo-helminth infection analysis. The prevalence of stunting was 40.4% and underweight was 28.4%. A total of 127 schoolchildren (69.4%) were positive for at least one of the 3 geo-helminth infections. The most common geo-helminth was Ascaris lumbricoides (62.8%), followed by Trichuris trichiura (38.9%), and hookworm infection was relatively low (12.6%). All the anthropometric indices measured were lower in the geo-helminth infected children compared to the uninfected childen, except for the weight-for-height z-score. However the differences were insignificant Geo-helminth infections may not be a significant factor in malnutrition of these schoolchildren. However, with the availability of safe, efficacious and cheap broad spectrum anthelmintics, regular mass treatment should be given in selected areas where the prevalence of geo-helminth infections is still high, so that these schoolchildren will be able to achieve their growth potential during their school years.

Ascariasis↗

Prevalence of soil transmitted helminthes infections among Bangladeshi males seeking job abroad.

This cross-sectional study was undertaken to identify the prevalence of soil transmitted helminthes infections and its relation to socio-demographic characteristics among Bangladeshi males seeking job abroad. The stool sample of each respondent coming for medical check up was collected by code number and examined under microscope to see the presence helminthic ova or larvae. Among 8140 respondents, 68.05% were from rural and 31.95% from urban area. As a whole, helminthic infection was found in 20.22% respondents. Off which rural and urban distribution were 27.58% and 5.22% respectively (p<0.001). Pattern of helminthes as per rural and urban basis were as follows: Ascaris lumbricoides in 12.45% & 2.61%, Trichuris trichurias in 2.61% & 2.50% samples respectively. As per age distribution was concerned, number of positive cases among rural population in all age groups was statistically higher (p<0.001) than that of urban population. Similarly, rate of combined infections among the rural population was also statistically higher (p<0.001). Higher positivity of helminthes was obtained in low-level educated respondents and in the farmers group. Since the study reflected a high proportion of helminthes infections in rural people, so it was recommended to launch regular deworming programme in rural community at national level. Health education activities on proper sanitary practice, safe disposal of excreta and taking safe food-drinks should be meaningful to eradicating helminthes infections. Further study is needed for monitoring the active status in the community.

Adult↗

Soil-transmitted helminthic infection and its effect on nutritional status of adolescent schoolgirls of low socioeconomic status in Sri Lanka.

The prevalence of soil-transmitted helminthic infection, living conditions, and practices relating to personal hygiene were studied in schoolgirls (age 14-18 years) in both an urban area (n = 383) and a rural area (n = 231) of Sri Lanka. The impact of helminthic infection on nutritional status was also studied. The prevalence of Ascaris and Trichuris infection was significantly higher (p < 0.00001) in the urban area than in the rural area and this was associated with poor living conditions and personal hygiene. In contrast, the prevalence of hookworm infection was similar in the two areas. Less than 3 per cent of subjects had moderate or heavy infection. Trichuriasis was the commonest helminthic infection and was associated with significantly lower serum vitamin A concentrations than in uninfected subjects. There was no significant difference in body mass index or haemoglobin concentration between infected and uninfected subjects. Our results show that even mild infection with Trichuris had adverse effects on vitamin A status.

Adolescent↗

Helminthic infection and anthropometric indicators in children from a tropical slum: Ascaris reinfection after anthelmintic treatment.

We evaluated helminthic infection and anthropometric indicators of nutritional status in a group of school-age children from a slum area of Caracas, Venezuela. The proportions of children at or below the 10th percentiles for height/age and weight/age were significantly higher in those presenting helminthiasis than in those uninfected. Although this could partially reflect a codependence of both helminthic infection and undernutrition or poverty, when the children were administered regular anthelmintic treatment for a year their anthropometric values improved significantly. When they were re-evaluated 8 months after the end of anthelmintic administration, the degree of reinfection by the most common helminth, Ascaris lumbricoides, was significantly higher in the growth-retarded children. These results confirm the relationship between helminthic infection and decreased growth rates in underprivileged populations, and indicate that children at nutritional risk are more susceptible to such infections, even after a prolonged parasite-free period.

Anthelmintics↗

Global epidemiology, ecology and control of soil-transmitted helminth infections.

Soil-transmitted helminth (STH) infections are among the most prevalent of chronic human infections worldwide. Based on the demonstrable impact on child development, there is a global commitment to finance and implement control strategies with a focus on school-based chemotherapy programmes. The major obstacle to the implementation of cost-effective control is the lack of accurate descriptions of the geographical distribution of infection. In recent years, considerable progress has been made in the use of geographical information systems (GIS) and remote sensing (RS) to better understand helminth ecology and epidemiology, and to develop low-cost ways to identify target populations for treatment. This review explores how this information has been used practically to guide large-scale control programmes. The use of satellite-derived environmental data has yielded new insights into the ecology of infection at a geographical scale that has proven impossible to address using more traditional approaches, and has in turn allowed spatial distributions of infection prevalence to be predicted robustly by statistical approaches. GIS/RS have increasingly been used in the context of large-scale helminth control programmes, including not only STH infections but also those focusing on schistosomiasis, filariasis and onchocerciasis. The experience indicates that GIS/RS provides a cost-effective approach to designing and monitoring programmes at realistic scales. Importantly, the use of this approach has begun to transition from being a specialist approach of international vertical programmes to becoming a routine tool in developing public sector control programmes. GIS/RS is used here to describe the global distribution of STH infections and to estimate the number of infections in school-age children in sub-Saharan Africa (89.9 million) and the annual cost of providing a single anthelmintic treatment using a school-based approach (US$5.0-7.6 million). These are the first estimates at a continental scale to explicitly include the fine spatial distribution of infection prevalence and population, and suggest that traditional methods have overestimated the situation. The results suggest that continent-wide control of parasites is, from a financial perspective, an attainable goal.

Africa South of the Sahara↗

Parallel regulation of IL-4 and IL-5 in human helminth infections.

To investigate the relationship between cytokine production and the increased levels of serum IgE and peripheral eosinophilia commonly accompanying human helminth infections, we studied the ability of PBMC of normal (N1) (n = 18) and eosinophilic individuals with helminth infections (H1) (n = 9) to produce IL-3, IL-4, IL-5, granulocyte-macrophage-CSF, and IFN-gamma in vitro after stimulation with PMA (50 ng/ml) and ionomycin (1 microgram/ml). The two groups differed in both the levels of serum IgE and eosinophilia. For mitogen-induced production of granulocyte-macrophage-CSF and IFN-gamma, there was no difference in cytokine production between the two groups. In marked contrast, supernatants from PBMC of infected individuals had significantly higher levels of IL-4 (mean = 213 pg/ml for N1 and 944 pg/ml for H1, p less than 0.02), IL-5 (mean = 180 pg/ml for N1 and 1118 pg/ml for HL, p less than 0.001), and IL-3 (mean = 13900 pg/ml for N1, 28029 pg/ml for H1, p less than 0.05). In addition, helminth-infected patients had approximately 5-fold greater numbers of T cells capable of producing IL-5 and 2.5-fold greater frequency of IL-4-secreting cells than did normal individuals; GM-CSF- and IFN-gamma-producing T cell numbers were not significantly different in the two groups. IL-3-producing cell frequencies could not be evaluated by this method. There was a direct correlation between IL-4 production and IL-5 production at the level of both protein production and frequency of T cells capable of producing these cytokines. These data indicate that individuals with reactive eosinophilia and elevated serum IgE have an expanded population of lymphocytes producing IL-4 and IL-5 and the association of the two suggests that the regulation of IL-4 and IL-5 may be linked.

CD4-Positive T-Lymphocytes↗

Factors influencing self-diagnosis and treatment of perceived helminthic infection in a rural Guatemalan community.

Changes in the diagnosis and treatment of helminthic infection were examined during a longitudinal study in a rural community in Guatemala. Self-diagnosis was predominant, with an increase in perceived helminthic infection during an economic crisis within the community. Allium sativum L. and Chenopodium ambrosoides L. were used as anthelmintics, often in conjunction with commercial drugs. During the economic crisis the use of plants as treatment for perceived infection increased whereas use of commercial helminthic medicine decreased. Dietary modifications were observed during periods of perceived infection, but were not consistent in the food items modified or the nature of the modification. Within the community individuals exhibited considerable heterogenity in their approaches to treatment.

Adolescent↗

Helminth infections are associated with protection from malaria-related acute renal failure and jaundice in Thailand.

Following studies showing an association between helminth infections and protection from cerebral malaria, we compared 22 patients with malaria-associated acute renal failure with 157 patients with moderately severe malaria. Helminths were associated with protection from renal failure (adjusted odds ratio [AOR], 0.16 [0.03-0.85], P = 0.03). Helminth-infected controls were less likely to have jaundice (AOR, 0.39 [0.16-0.96], P = 0.04) or to have peripheral mature schizonts (AOR, 0.2 [0.07-0.62], P = 0.005) than controls without helminths. This suggested that preexisting helminth infections may have been protective by influencing sequestration and obstructive jaundice, 2 possible determinants of acute tubular necrosis.

Acute Kidney Injury↗

Albendazole in the treatment of opisthorchiasis and concomitant intestinal helminthic infections.

A total of 52 adult patients with opisthorchiasis with or without concomitant intestinal helminthic infections were treated with albendazole at dosage regimens of 400 mg twice daily for 3 days (group I with 25 patients) and 7 days (group II 27 patients). By concentration method with four examinations from two faecal specimens of each patient the cure rates and percentage egg reduction on day 30 in group I and group II were 12% and 33%, 94 and 95 respectively; by Stoll method the cure rates and percentage egg reduction were 40% and 63%, 92 and 92 in group I and group II, respectively. There were no statistically significant differences between the results of the two regimens. Twenty six patients with hookworm and 9 patients with S. stercolaris infections were cured. Opisthorchis viverrini, N. americanus, A. duodenale, A. ceylanicum, E. malayanum, E. ilocanum, S. stercolaris, E. vermicularis, and T. saginata segments were expelled in stools, mostly on days 1 to 4. Most of the patients felt relieved from symptoms of pain in the right hypochondrium and epigastrium. The side effects were mild and transient. There were no evidence of toxic effects on the bone marrow, heart, liver or kidneys. Albendazole was shown to be effective against Opisthorchis viverrini infection as well as other concomitant intestinal helminthic infections; but the optimal dosage and duration of treatment have not yet been achieved.

Adolescent↗

Helminth infection is not associated with faster progression of HIV disease in coinfected adults in Uganda.

BACKGROUND: We studied a cohort of human immunodeficiency virus (HIV)-infected adults in Uganda who were not receiving antiretroviral therapy, to explore the impact of helminths on HIV progression in areas where antiretrovirals are not available. METHODS: A total of 663 patients were screened for helminths, treated presumptively with albendazole and selectively with praziquantel, and monitored for 6 months. Blood samples were analyzed for CD4+ cell count and HIV-1 RNA. RESULTS: Schistosoma mansoni, hookworm, Strongyloides stercoralis, and Mansonella perstans were the most prevalent helminths. Helminth infection was not associated with higher viral load, lower CD4+ cell count, or faster decrease in CD4+ cell count preceding antihelminthic therapy. The effect of coinfection on HIV disease progression varied with species. CD4+ cell counts were highest in subjects with hookworm and Mansonella perstans infection. For most helminths, effective treatment was associated with greater decrease in CD4+ cell count than in those in whom infection was still present at follow-up. A highly significant decrease in viral load at 6 months was seen in patients with persistent Mansonella perstans infection at follow-up. Mortality was lower in subjects with hookworm infection at enrollment. CONCLUSION: Helminth infection was not associated with more-advanced HIV disease or faster disease progression. Antihelminthic therapy may not be beneficial in slowing HIV progression in coinfected adults.

Adult↗

Recent patterns of intestinal helminth infections among the residents in Taegu City, Korea.

In order to estimate the recent pattens of intestinal helminth infections among the residents in Taege City, Korea, a survey based on discovery of helminth eggs by formalin-ether sedimentation and modified Graham's scotch-tape anal swab techniques, were performed during the period from March to September in 1983. A total of 1,697 fecal specimens were collected from 854 male and 843 female residents from 5 villages(Dong), each of whom were selected randomly to represent 1,000 persons referred to the census in 1982. Among the specimens examined, one or more species of helminth parasites were found in 473, revealing the overall positive rate of 27.9 pre cent. Of them, Trichuris trichiura was found most frequently, in 13.2 percent, followed by Enterobius vermicularis in 7.0 per cent. Hookworm was the least prevalent. The sex-specific rate of overall helminth infections was a little higher in females than in males, while in cases of Clonorchis sinensis, Metagonimus yokogawai and Taenia species, the infection rates in males was higher than in females. T.trichiura was most prevalent in the 20~29 age group and showed about the same prevalence in males and females of all age groups. C. sinensis infection rate increased with age while those of Ascaris lumbricoides decreased. Single infections were 82.5 per cent of all positive cases. Of cource, T. trichiura revealed the highest prevalence in 31.7 per cent followed by E. vermicularis in 20.1 per cent and A. lumbricoides in 14.8 per cent. Of the double infections, the percentage of T. trichiura in combination with other intestinal helminths was higher than that of A. lumbricoides. It was concluded that although the infection rates of intestinal helminths among the residents in Taegu City, Korea is still high, eradication of these parasitic diseases seems to be possible with twice-a-year administration of specific anthelmintics, in combination with extensive public health education and improvement of the dietary life.

Journal Article↗

Helminthic infection down-regulates type 1 immune responses in human T cell lymphotropic virus type 1 (HTLV-1) carriers and is more prevalent in HTLV-1 carriers than in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.

Human T cell lymphotropic virus type 1 (HTLV-1) infection is associated with an exacerbated type 1 immune response and secretion of high levels of proinflammatory cytokines. In contrast, helminthic infection induces a type 2 immune response. In the present study, the cytokine profile in HTLV-1 carriers coinfected with helminths (Strongyloides stercoralis and/or Schistosoma mansoni) was compared with that in HTLV-1 carriers not coinfected with helminths. Levels of interferon (IFN)- gamma were higher in HTLV-1 carriers not coinfected with helminths than in HTLV-1 carriers coinfected with helminths (P<.05). The overall frequency of IFN- gamma -expressing CD8+ and CD4+ cells was decreased in HTLV-1 carriers coinfected with helminths (P<.05). The percentage of interleukin (IL)-5- and IL-10-expressing T cells in HTLV-1 carriers coinfected with helminths was higher than that in HTLV-1 carriers not coinfected with helminths (P<.05). Moreover, we found that the prevalence of helminthic infection was 7-fold higher in HTLV-1 carriers than in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (P<.05). These data show that helminthic infection decreases activation of type 1 cells, which may influence the clinical outcome of HTLV-1 infection.

Adult↗

A theoretical framework for immune responses and predisposition to helminth infection.

Many field studies of human helminth infections have reported a positive correlation between parasite burdens and the rate of re-establishment of infection following chemotherapy, i.e., predisposition. Some studies have also reported the relationships between re-establishment and exposure and immune responses. The interpretation of these data is made difficult by the complexity of the underlying immunoepidemiological processes. In this paper, simple mathematical models are used to explore expected patterns, especially in relation to host age. These patterns are determined by rates of infection, parasite life expectancy, the level of immunological responsiveness, the duration of immunological memory, and may be greatly affected by the immunogenic roles of different parasite stages. In general, acquired immunity is predicted to reduce the degree of predisposition. This reduction is age-dependent and may generate 'negative predisposition' in some age classes. Age-dependent reductions in the correlation between re-establishment and exposure are also predicted. The correlation between re-establishment and protective immune responses is also predicted to be age-dependent, but may remain positive for all ages despite significant acquired immunity. The results suggest that great care is needed in the interpretation of immunoepidemiological data from treatment-reinfection studies.

Adolescent↗

Effect of low-level pathogenic helminth infection on energy metabolism in Gambian children.

The aim of the present study was to determine whether an increase in resting energy expenditure (REE) contributes to the impaired nutritional status of Gambian children infected by a low level of infection with pathogenic helminths. The REE of 24 children infected with hookworm, Ascaris, Strongyloides, or Trichuris (mean +/- SEM age = 11.9 +/- 0.1 years) and eight controls without infection (mean +/- SEM age = 11.8 +/- 0.1 years) were measured by indirect calorimetry with a hood system (test A). This measurement was repeated after treatment with 400 mg of albendazole (patients) or a placebo (controls) (test B). When normalized for fat free mass, REE in test A was not different in the patients (177 +/- 2 kJ/kg x day) and in the controls (164 +/- 7 kJ/kg x day); furthermore, REE did not change significantly after treatment in the patients (173 +/- 3 kJ/kg x day) or in the controls (160 +/- 8 kJ/kg x day). There was no significant difference in the respiratory quotient between patients and controls, nor between tests A and B. It is concluded that a low level of helminth infection does not affect significantly the energy metabolism of Gambian children.

Anthropometry↗

Low risk for helminth infection in wastewater-fed rice cultivation in Vietnam.

This study was done to assess the risk of helminth infection in association with wastewater-fed rice cultivation in an agricultural setting of Nam Dinh city, Vietnam. In a cross sectional survey data were collected for 202 households in a commune where wastewater was used for irrigation and for 201 households in a commune that used river water. Parasitological examination was conducted on single stool samples obtained from 1,088 individuals aged -15 years from the households. The irrigation water used in both communes was enumerated for helminth eggs and thermotolerant coliforms. The prevalence of infection with Ascaris spp., Trichuris spp., and hookworm was 42.2%, 19.9% and 10.5% respectively, with an overall prevalence of infection with any helminth of 53.4%. Surprisingly, the prevalence of infection with Ascaris and Trichuris was lower among people exposed to wastewater (containing 40-200 helminth eggs/l and 10(4) thermotolerant coliforms/100 ml) compared to people exposed to river water that contained lower worm egg and bacterial numbers. Poor sanitation and hygiene practices and not using protective measures were important independent risk factors for helminth infection. For hookworm infection, no significant difference was observed between the wastewater exposed and unexposed groups. Children living in the wastewater use area had a significantly better nutritional status than those in the area using river water. This suggests a generally higher welfare level of the wastewater use area. In conclusion, this study showed no evidence that rice cultivation with wastewater poses a risk for helminth infection. More detailed studies are needed on the reduction of fecal indicators and helminth eggs in peri-urban wastewater-irrigated rice culture systems and on the relative importance of wastewater irrigation compared to other risk factors for human helminth infection such as poor sanitation and poverty.

Animals↗

Innate and cognate mechanisms of pulmonary eosinophilia in helminth infection.

Passage of helminth larvae through the lungs can cause pulmonary eosinophilia that may have evolved as a means of parasite attrition. If allergic responses represent a misdirected activation of this arm of the immune system, then mechanisms governing eosinophil recruitment during infection would be expected to be closely related to those seen in allergy. We studied primary Necator americanus infection and compared this to multiply-infected or vaccinated mice. The arrival of larvae in the lungs triggered rapid eosinophil recruitment, which was greatly enhanced in previously sensitized mice. Interestingly, the presence of larvae in the lung was sufficient to trigger eosinophil chemoattractant production, including the chemokines eotaxin and MIP-1alpha, and was not enhanced by prior exposure to the parasites. Infection stimulated IL-5 production in all groups; however, this and IgE production were greatly enhanced in sensitized animals. Elevated IL-5 increased bone marrow production of eosinophils, and eosinophilia was abrogated by treatment with anti-IL-5 antibody. Therefore, trapping of larvae in the pulmonary vasculature is sufficient to trigger eosinophil recruitment, by induction of chemokines and IL-5. Primed cognate Th2 immunity does not increase local chemokine production, but does increase IL-5 production, which greatly enhances the availability of eosinophils for recruitment to the lung.

Animals↗