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PubMed2006

Comparative immunology of human and animal models of hookworm infection.

Hookworm infection is a major cause of disease burden for animals and humans. Over the past years, the use of animal models in hookworm infections has been driven by the search of new anthelminthic therapies and, especially, vaccine development. These studies also contributed to the advance of knowledge on immunity to hookworms, offering new insights to understand the nature of this parasitic infection. In this article, we will summarize the essential features of the immune response in the two major animal models of hookworm infections (dog and hamster) and then consider its implication for the human immune response.

Ancylostoma↗

PubMed2001

Immune responses in hookworm infections.

Hookworms infect perhaps one-fifth of the entire human population, yet little is known about their interaction with our immune system. The two major species are Necator americanus, which is adapted to tropical conditions, and Ancylostoma duodenale, which predominates in more temperate zones. While having many common features, they also differ in several key aspects of their biology. Host immune responses are triggered by larval invasion of the skin, larval migration through the circulation and lungs, and worm establishment in the intestine, where adult worms feed on blood and mucosa while injecting various molecules that facilitate feeding and modulate host protective responses. Despite repeated exposure, protective immunity does not seem to develop in humans, so that infections occur in all age groups (depending on exposure patterns) and tend to be prolonged. Responses to both larval and adult worms have a characteristic T-helper type 2 profile, with activated mast cells in the gut mucosa, elevated levels of circulating immunoglobulin E, and eosinophilia in the peripheral blood and local tissues, features also characteristic of type I hypersensitivity reactions. The longevity of adult hookworms is determined probably more by parasite genetics than by host immunity. However, many of the proteins released by the parasites seem to have immunomodulatory activity, presumably for self-protection. Advances in molecular biotechnology enable the identification and characterization of increasing numbers of these parasite molecules and should enhance our detailed understanding of the protective and pathogenetic mechanisms in hookworm infections.

Ancylostomatoidea↗

PubMed2005

Immunobiology of hookworm infection.

Hookworms infect almost one billion people and are a major cause of iron-deficiency anaemia in developing countries of the tropics. Despite their prevalence and the morbidity they cause, little is known about the immune response to this complex eukaryotic parasite. Recent publications have shed light on the human cellular immune responses to hookworms, as well as mechanisms that hookworms utilize to skew the immune response in its favour. Unlike most other human helminth infections, neither age- nor exposure-related immunity develops in the majority of infected people. A vaccine is therefore a highly desirable goal. To this end, gene sequencing efforts have resulted in the deposition of more than 10,000 hookworm cDNA sequences in the public domain, providing a molecular snapshot of this intriguing parasite and providing novel tools for the development of new control strategies. Significant progress has been made in the development of anti-hookworm recombinant vaccines, and clinical trials are expected to begin in the near future.

Ancylostoma↗

PubMed2005

X-ray structure of Na-ASP-2, a pathogenesis-related-1 protein from the nematode parasite, Necator americanus, and a vaccine antigen for human hookworm infection.

Human hookworm infection is a major cause of anemia and malnutrition of adults and children in the developing world. As part of on-going efforts to control hookworm infection, The Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective L3 larval stages of the parasite, including a family of pathogenesis-related (PR) proteins known as the Ancylostoma-secreted proteins (ASPs). A novel crystal structure of Na-ASP-2, a PR-1 protein secreted by infective larvae of the human hookworm Necator americanus, has been solved to resolution limits of 1.68 A and to an R-factor of 17% using the recombinant protein expressed in and secreted by Pichia pastoris. The overall fold of Na-ASP-2 is a three-layer alphabetaalpha sandwich flanked by an N-terminal loop and a short, cysteine-rich C terminus. Our structure reveals a large central cavity that is flanked by His129 and Glu106, two residues that are well conserved in all parasitic nematode L3 ASPs. Na-ASP-2 has structural and charge similarities to chemokines, which suggests that Na-ASP-2 may be an extra-cellular ligand of an unknown receptor. Na-ASP-2 is a useful homology model for NIF, a natural antagonistic ligand of CR3 receptor. From these modeling studies, possible binding modes were predicted. In addition, this first structure of a PR-1 protein from parasitic helminths may shed light on the molecular basis of host-parasite interactions.

Amino Acid Sequence↗

PubMed1999

Evidence for an association between hookworm infection and cognitive function in Indonesian school children.

The association between helminth infection and cognitive and motor function was investigated in school-age children in Java, Indonesia. 432 children from 42 primary schools participated in the study. Children were stratified by age and sex into two age groups, 8-9 years and 11-13 years. Children infected with hookworm performed significantly worse than children without hookworm infection in 6 of the 14 cognitive or motor tests. After controlling for school (as a random effect) plus age, socio-economic status and parental education, sex, stunting (height-for-age < - 2sd), body mass index, haemoglobin concentration and the presence of A. lumbricoides and T. trichiura infections, infection with hookworm explained significantly lower scores on tests of Fluency (P < 0.01), Digit-Span Forwards (P < 0.01), Number Choice (P < 0.01), Picture Search (P < 0.03), Stroop Colour Word (P < 0.02) and Mazes (P < 0.001). In 4 of the 6-tests (Fluency, Number Choice, Picture Search and Mazes), there was a significant interaction between hookworm infection and age (P < 0.03), indicating that the association between hookworm and lower test scores increased with age. No associations were observed between hookworm infection and scores in tests of Digit-Span Backwards, Corsi-Block, Stroop Colour, Stroop Interference, Free Recall, Verbal Analogies, Bead Threading or the Pegboard (P > 0.05). Tests associated with helminths represented various functions of working memory. No significant associations between helminth infection and motor function were observed that could not be explained by chance. The results suggest that hookworm infection can have a significant adverse effect on children's working memory which may have consequences for a child's reasoning ability and reading comprehension. Although the results are only associational, the fact that differences in cognition were observed at baseline imply that preventing infection with helminths in school-age children could be of benefit.

Adolescent↗

PubMed1999

Geographic distribution and epidemiology of Oesophagostomum bifurcum and hookworm infections in humans in Togo.

In contrast to the rest of the world, infections with Oesophagostomum bifurcum are commonly found in humans in northern Togo and Ghana. In addition, infections with hookworm are endemic in this region. In the present study, a detailed map of the geographic distribution of O. bifurcum and hookworm infections in northern Togo was made. There were a number of foci with high prevalence of infection with O. bifurcum. All the villages examined were infected with hookworm, and the distribution was quite patchy. Women were infected with O. bifurcum more often than men, while infections with hookworm were more prevalent in men than in women. The prevalence and intensity of infection with both parasites were clearly age-dependent. We estimate that more than a 100,000 people in Togo are infected with O. bifurcum and more than 230,000 are infected with hookworm.

Adolescent↗

PubMed2005

The impact of concurrent and treated Ancylostoma ceylanicum hookworm infections on the immunogenicity of a recombinant hookworm vaccine in hamsters.

BACKGROUND: The effect of concurrent (active) and treated hookworm infections on the immunogenicity of vaccination with the recombinant fusion protein Ay-Ancylostoma-secreted protein 2 was analyzed in the Golden Syrian hamster. METHODS: Hamsters were infected with the hookworm Ancylostoma ceylanicum and vaccinated with the recombinant protein, with Quil A used as adjuvant. As controls, hookworm-infected hamsters were treated with the anthelmintic drug pyrantel pamoate before vaccination. Naive hamsters (i.e., those with neither previous hookworm infections nor treatment) were also vaccinated. RESULTS: The proliferation capacities of carboxyfluorescein diacetate succinimidyl ester-positive lymphocytes from the hookworm-infected vaccinated group were reduced by 50% relative to the capacities of lymphocytes from uninfected or treated vaccinated hamsters; capacities were comparable to the rates observed in lymphocytes from the hamsters vaccinated with the adjuvant alone. Immunoglobulin G1 antibody responses were also reduced in the actively infected, untreated hamsters, and interferon- gamma and interleukin-4 cytokine mRNAs were down-regulated. Conversely, interleukin-10 and tumor necrosis factor- alpha mRNAs were up-regulated in those hamsters. CONCLUSIONS: These results suggest that hookworm infections have an immunomodulatory effect by impairing the immune response to an exogenous antigen during infection. The hookworm-associated immunodepression may have important implications for design of clinical trials of human vaccines and vaccination strategies.

Adjuvants, Immunologic↗

PubMedDate not supplied

The immunoepidemiology of human hookworm infection.

Advances in hookworm immunoepidemiology are reviewed. Recent studies demonstrate a mixed Th1/Th2 response in human hookworm infection, with immunosuppression of specific and nonspecific IFN-gamma responses. There is increasing evidence for protective immunity in human hookworm infection, including anti-larval IL-5- and IgE-dependent mechanisms, and for immunological interactions between hookworm infection and other diseases.

Ancylostoma↗

PubMed2005

High risk of hookworm infection among wastewater farmers in Pakistan.

The health risks of wastewater use in agriculture were investigated in the city of Faisalabad, Pakistan, by means of a cross-sectional study. The study showed an increased risk of intestinal nematode infection and hookworm infection, in particular, in wastewater farmers (OR = 31.4, 95% CI 4.1-243) and their children (OR = 5.7, 95% CI 2.1-16) when compared with farming households using regular (non-wastewater) irrigation water. Textile labourers living in the same village as the wastewater farmers showed a lower risk of hookworm infection than wastewater farmers but an increased risk compared with farming households using regular irrigation water. Many urban and peri-urban farmers make a living by using untreated wastewater in the production of fresh produce for the urban market. Banning the use of untreated wastewater would deprive these farmers of their livelihood and affect food supply for the urban population. If treatment of wastewater is not a feasible option, the promotion of footwear and improved hygiene, the construction of toilets, in combination with regular anthelminthic treatment, would be suitable alternatives to safeguard the health of wastewater farmers and their children.

Adolescent↗

PubMed1981

The relationship of hookworm infection, anaemia and iron status in a Papua New Guinea highland population and the response to treatment with iron and mebendazole.

In 345 apparently healthy Papua New Guinea male subjects, predominantly highlanders, 89% of whom were infected with hookworm (Necator americanus), there was a statistically significant inverse correlation of hookworm egg count with haemoglobin and serum ferritin level, but no significant correlation with serum albumin, folate or B12 values. A sub-group of 128 was chosen for a six-month study on the effect of treatment with the anthelmintic mebendazole and/or parenteral iron on haemoglobin and serum ferritin levels. Mebendazole-treated subjects remained worm-free and the hookworm egg counts of the controls decreased during the study period. Parenteral iron treatment had the expected effect of raising haemoglobin to a normal level. There was a statistically significant improvement in haemoglobin level in all treated groups but not in the control. Serum ferritin levels decreased significantly in all groups, but more in the control than in the treated groups, although treatment groups were not significantly different. Although probable inadequate uptake of iron by the subjects and blood donation by some subjects was apparently more detrimental to iron status than hookworm infection, the results of this study support the view that hookworm infection in this country contributes to lowered haemoglobin levels and iron status.

Anemia, Hypochromic↗

PubMed1986

Changes in the structural and functional properties of human eosinophils during experimental hookworm infection.

Normal volunteers were infected with hookworm larvae Necator americanus. Peripheral blood counts showed a mean of 524 +/- 29 eosinophils/mm3 of blood before infection and a mean of 3,008 +/- 456 eosinophils/mm3 of blood during infection (P less than .01). Absolute numbers of neutrophils did not change. Eosinophils and neutrophils from the infected period were compared with the noninfected state in each subject. The percentage of hypodense eosinophils increased from a mean of 34% +/- 13% to 80% +/- 7% during infection (P less than .05). Superoxide production of eosinophils increased from a mean of 56 +/- 9 to 97 +/- 12 nmol of O2-./10(6) cells per 60 min (P less than .05) during infection. Chemotaxis of eosinophils to Escherichia coli endotoxin-activated serum increased from a mean average distance migrated of 19 +/- 2 micron (P less than .05), whereas neutrophil responsiveness did not change. This is the first report of changes in eosinophil density and stimulation of eosinophil function in normal hosts experimentally infected with hookworm. The data indicate that hookworm infection preferentially increases eosinophil production and activity with little effect on neutrophils.

Chemotaxis, Leukocyte↗

PubMed1992

[Differential diagnostic value of occult blood in stool in hookworm infection in the Third World. Study from Papua New Guinea].

In 633 persons of the Madang province in Papua-New Guinea hookworm-infection, blood hemoglobin and the presence of blood in stools were studied. 60% of the subjects were infected with hookworm (Necator americanus). There was a significant linear correlation between the intensity of hookworm infection and blood haemoglobin level. The Colo-Rectal test gave positive results in 17% of the cases without worm-infection. In infected persons, the Colo-Rectal test gave an increasing rate of positive results as the parasite infection increased: 24% for subjects with low levels of infection, and 57% and 67% for moderate and high levels, respectively. The mean blood-haemoglobin level was lower in persons with positive Colo-Rectal-Test and hookworm infection (11.8 g%) than among those with negative Colo-Rectal-Test and hookworm infection (15.0 g%, p < 0.01). In young populations with a known high prevalence of hookworm infection, Colo-Rectal test is therefore suitable for the detection of moderate or severe hookworm infections. It may serve as a simple and useful method to work up anaemia is such populations.

Adolescent↗

PubMed2002

Association between Schistosoma mansoni and hookworm infections among schoolchildren in Côte d'Ivoire.

Infections with Schistosoma mansoni and hookworms are widespread in sub-Saharan Africa and the burden of disease associated with both parasites is enormous. Although there is a large overlap in their geographic distribution, little is known about the association between S. mansoni and hookworm infections and the underlying mechanisms. We explored this association among 325 schoolchildren from Côte d'Ivoire, by screening multiple stool specimens over consecutive days. We found a highly significant positive association between S. mansoni and hookworm infections with an adjusted odds ratio of 2.25 (95% confidence interval: 1.31-3.85; P=0.003). Increasing infection intensity of S. mansoni was significantly correlated with an increased likelihood of concomitant hookworm infections (chi(2)=20.72; P<0.001). Egg counts in stool specimens derived from a single day did not consistently reveal the positive association between the two parasites, which underlines the importance of repeated stool examinations. Several self-reported water contact patterns were significantly associated either with S. mansoni, hookworm or concomitant infections. Our findings are of considerable importance for tailoring effective health education messages that are readily adapted to the local epidemiological setting. Complemented with other control interventions, these measures might significantly reduce the burden caused by S. mansoni and hookworm infections.

Adolescent↗

PubMed1997

Hookworm infection and disease: advances for control.

Advances in epidemiology and in control strategies of hookworm infection and associated disease were reviewed. Recent estimates indicate that hookworms infect approximately 1.3 billion people worldwide, and 96 million suffer from associated morbidity, including also insidious effects on nutritional status and on physical and intellectual development. Recent research studies on iron loss and iron-deficiency anaemia associated to hookworm infection were irondeficiency anemia associated to hookworm infection were reviewed. Recommendations for planning strategies for the control of hookworm infection were addressed and epidemiology, targets, chemotherapy, health education, sanitation, monitoring and evaluation in helminth control programmes were discussed. Special relevance was given to chemotherapy with new, single dose broad spectrum, safe anthelminthic drugs as the mainstay of control strategy to reduce intensity of infection, iron-deficiency anaemia and other morbidity indicators associated with hookworm infections. For the control of transmission of hookworm infection, periodic chemotherapy should be implemented in the context of ongoing improvement of sanitation and promotion of health education. These elements should be integrated into the prevailing system of primary health care and must be based on multisectoral collaboration to ensure sustainability of control programmes.

Ancylostoma↗

PubMed1993

Hookworm infection and iron stores: a survey in a rural community in Bali, Indonesia.

A study of the rural population of the village of Belumbang, Province of Bali, Indonesia, has been conducted to assess the relationship between intensity of hookworm infection (hookworm egg count) and iron stores, hemoglobin level or hematocrit. There was a significant negative correlation between serum ferritin level and hookworm egg count. However no correlation was found between hookworm egg count and hemoglobin level or hematocrit. In a separate analysis the above correlation could be shown in male hosts but not in female hosts. It is concluded that hookworm infection, even in light infection, can interfere with iron stores, but in female hosts this effect might be masked by other factors.

Anemia, Hypochromic↗

PubMed1978

[Epidemiological Study On The Hookworm Infections In Korea]

This study was undertaken to evaluate the present status of hookworm infections in Korea from October 1976 through September 1978. The stool specimens of 5,632 persons(male 3,689: female 1,943) collected from primary and middle schools, foundling asylums, and the general populations of various parts in Korea were examined The methods employed were brine floatation technique for the prevalence rate of hookworm infections, Kato's cellophane thick smear technique for the other helminthic infections, and Stoll's dilution egg counting technique for the intensity of hookworm infections. Ancylostoma duodenale and Necator americanus infections were classified by polyethylene tube coproculture method and by the evacuated adult worms after administration of anthelmintics against the patients infected with hookworms. The following results were obtained in this study. 1. The prevalence rate of hookworm infections in rural area was higher than in urban area in the ratio of 2.4:1. And in the age group of over 20, the prevalence rate in significantly higher than that in urban area in the ratio of 5.8:1. 2. In the urban area, difference in the prevalence rate of hookworm infections between the age group of over 20 and that of under 19 was not observed. But in the rural area, the ratio of the prevalence rate between the age group of over 20 to that of under 19 was 8:1. 3. The prevalence rate of hookworm infections in female was higher than that in male in all age group except the age group of under 9 and 20~29. The ratio of the prevalence rate between female to male was 1.5:1 in total population. 4. The area which showed the mean E.P.G. of over 1,000 was not found and almost all of the patients who were infected with hookworms gave the mean E.P.G. between l~999. 5. Necator americanus was newly found in Dangjin Gun, Boseong Gun, Habcheon Gun and Weonseong Gun. In these 4 newly found areas, Dangjin Gun and Boseong Gun showed the composition rate of 25.5% and 83.4% respectively.

Journal Article↗

PubMed2005

Risk factors and spatial patterns of hookworm infection among schoolchildren in a rural area of western Côte d'Ivoire.

This study is aimed at investigating the risk factors for hookworm infection among schoolchildren in a rural area of western Côte d'Ivoire and predicting and mapping the spatial distribution of infection. We used demographic and socio-economic data from a cross-sectional survey of 6-16-year-old schoolchildren from 56 schools. Infection with hookworm was determined by microscopic examination of stool samples employing the Kato-Katz technique and an ether-concentration method. Environmental data were derived from satellite images and digitised maps. Bayesian variogram models were applied to investigate the variation of hookworm infection in relation to demographic, socio-economic and environmental factors. The overall hookworm infection prevalence, based on the pooled microscopic diagnoses, was 43.3% and ranged from 5.4 to 79.1% in the schools surveyed. Bivariate analyses showed that sex, age, socio-economic status, elevation, rainfall and land cover were significantly associated with the spatial distribution of hookworm infection. The final multivariate spatial model consisted of the covariates age, sex, socio-economic status, elevation and land cover. When assuming non-stationary underlying spatial dependency, the results of the model suggested that spatial correlation depended on the location only marginally. We conclude that, at the current resolution, it seems more reasonable to target interventions based on well-established epidemiologic risk factors, rather than on spatial factors.

Adolescent↗

PubMed1999

Epidemiology of human hookworm infections among adult villagers in Hejiang and Santai Counties, Sichuan Province, China.

Hookworm infection as well as other intestinal nematodiases are endemic to Sichuan Province in China. In order to research the prevalence and intensity of these infections we visited two villages in Hejiang County (southern Sichuan Province) and Santai County (northwestern Sichuan Province) between July and October of 1997. Fecal examinations were performed on adult villagers over the age of 15 years (currently children under this age are dewormed annually with anthelmintic drugs). Among 310 residents of Lugao Village (Hejiang County), 87, 63 and 60% were infected with hookworm, Ascaris or Trichuris, respectively. The prevalence of hookworm determined to rise linearly with age (r = 0.97). High intensity infections with hookworm still occur in this region as 22% of the residents have over 3000 eggs per gram (PEG) of feces as determined by quantitative egg counts. The majority of these individuals harbored mixed infection with Necator americanus and Ancylostoma duodenale, although the former predominated when adult hookworms were collected from 30 village residents treated with pyrantel pamoate. In contrast, among the 334 Xinjian villagers examined (Santai County) the majority harbored predominantly light hookworm infections--66.1% of the residents has less than 400 EPG by quantitative fecal examination and only 3.7% exhibited greater than 3000 EPG. Again, N. americanus was the predominant hookworm seen after worm expulsion. We have round that despite economic development which is occurring in some parts of China, significant hookworm infections and clinical hookworm anemia still exist in areas of Sichuan Province. In Hejiang County we found that the intensity of hookworm infection has actually risen within the last 10 years. Hookworm is a medical problem among the elderly in Sichuan.

Adolescent↗