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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↗

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↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗

[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↗

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↗

A comparative study on the efficacy of albendazole and mebendazole in the treatment of ascariasis, hookworm infection and trichuriasis.

A comparative study of the efficacy of albendazole and mebendazole was carried out in Pattani Province in the southern part of Thailand. One hundred and ninety-six patients with single or multiple infections with Ascaris, hookworm, and Trichuris were randomized into 4 groups for different treatments. Stool examination by Kato-Katz technique were done before and on day 14 after treatment. Results of the study showed that (1) a single dose of 300 mg mebendazole (locally produced) resulted in cure rates of 50%, 0% and 0% and egg reduction rates of 87.3%, -15.3%, and 28.3%, for ascariasis, hookworm infection and Trichuris respectively; (2) a single dose of 300 mg mebendazole (original) resulted in cure rates of 100.0%, 9.1%, and 43.3%, and egg reduction rates of 100.0%, 72.0%, and 77.9%, for Ascaris, hookworm, and Trichuris respectively; (3) a single dose 500 mg mebendazole (original) resulted in cure rates of 100.0%, 30.2%, and 70.3%, and egg reduction rates of 100.0%, 70.4% and 89.9%, for Ascaris, hookworm, and Trichuris respectively and (4) a single dose of 400 mg albendazole (original) resulted in cure rates of 100.0%, 84.3%, and 67.4%, and egg reduction rates of 100.0%, 96.0% and 87.0%, for Ascaris, hookworm, and Trichuris respectively. Both mebendazole and albendazole are safe and no side effects were observed. The results of this study suggested that albendazole is the preferred benzimidazole derivative for mass treatment of multiple infections with Ascaris, hookworm, and Trichuris.

Adolescent↗

A randomized controlled trial comparing mebendazole and albendazole against Ascaris, Trichuris and hookworm infections.

The efficacies and side effects of single dose treatments with 500 mg mebendazole (Janssen Pharmaceutica) and 400 mg albendazole (SmithKline Beecham) against intestinal nematodes were compared in a single-blind, randomized controlled trial among 2294 children aged 6 to 12 years on Pemba Island, Zanzibar, among whom infections with Ascaris, hookworms and Trichuris were highly prevalent. Both drugs were highly effective against Ascaris, with cure rates of over 97%. The cure rates for Trichuris were low, but mebendazole was significantly better than albendazole and produced a greater reduction in the geometric mean egg count. Mebendazole was inferior to albendazole in curing hookworm infections and in reducing the geometric mean egg count. There was no difference in the frequency of side effects reported by heavily infected children treated with either drug. In a trial on 402 children, 500 mg mebendazole (Janssen) was compared with a generic version of the drug, 500 mg mebendazole (Pharmamed). No difference was apparent in the efficacies of the 2 treatments against any of the 3 parasites studied.

Albendazole↗

Response of dogs to challenge with Ancylostoma ceylanicum during the tenure of a primary hookworm infection.

A model of human hookworm infection has been developed which shows that dogs currently infected with small numbers of hookworms are considerably resistant to a challenge infection with a large inoculum of infective larvae. Two groups of dogs were infected with 500 larvae and four weeks after infection one group together with a previously uninfected control group were infected with 5,000 larvae and followed for six weeks. When compared with the secondary infection control dogs, faecal egg excretion and adult worm burdens were reduced by an average of 83 and 78% respectively. Infections had no significant effect on total white cell counts, platelet levels or spontaneous, phytohaemagglutinin- and antigen-induced lymphocyte transformation among the three groups of dogs. Dogs previously uninfected with hookworm developed a marked anaemia when infected with 5,000 larvae but this was not observed in the superinfected group. An eosinophilia developed in all groups and there were no significant differences among the three groups of animals. Specific IgM antibodies developed transiently in all groups of dogs two weeks after infection. IgG antibody levels were significantly greater in the superinfected animals one, two and three weeks after challenge infection compared with the secondary infection control animals; by four weeks there was no significant difference between the two groups of animals. Both groups given the large inoculum of larvae developed specific IgA antibodies one week after the challenge infection and these continued to rise in the superinfected group until termination of the experiment. It is concluded that dogs currently infected with the hookworm, Ancylostoma ceylanicum, demonstrate the development of functional protective immunity.

Ancylostomiasis↗

Prevalence of hookworm infection, anaemia and faecal blood loss among the Yupno people of Papua New Guinea.

The present report describes a study of hookworm infection, anaemia and the presence of blood in stool among the inhabitants of the Yupno area in Madang Province, Papua New Guinea. The study group comprised 588 persons of all age groups. A second group of 45 patients attending the Madang General Hospital, in the provincial capital on the coast, was used for comparison. In the Yupno area, 59% of the subjects were infected with hookworm; in the coastal group the infection rate was 82%, which was significantly higher. There is therefore a moderate prevalence of hookworm infection in the Yupno area, which does not impair the health of the population to any great extent. In both places there was a clear increase in the infection rate between the group of children 1-5 years old and the older groups. The mean blood haemoglobin level was 15.1 g/dl among the Yupno, which was significantly higher than that of the second group (10.7 g/dl). There was a significant negative linear correlation between the intensity of hookworm infection and blood haemoglobin level. The Colo-Rectal-Test for blood in stool was used on samples from 145 persons in the Yupno and from 43 in the coastal group. The 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 burden increased: 24% for subjects with low levels of infection, and 57% and 67% for moderate and high levels, respectively. The Colo-Rectal-Test is therefore a simple method for the detection of faecal blood loss in populations with a high prevalence of hookworm infection. However, it is not useful as an instrument for general screening for hookworm infections.

Adolescent↗

Secretory IgA and complement levels in patients with hookworm infection in Zaria.

As a continuing investigation into the immunological reactions involved in hookworm infection the levels of secretory IgA (sIgA). IgM, IgA, complement C3 and C4 were studied in 57 Nigerians with hookworm infection and compared with those of 28 healthy, normal controls. The hookworm patients were divided into three groups based on the degree of anaemia (Hb1-7 and hypochromia +++). Group II had moderate anaemia (Hb8-11, hypochromia ++ and Group III had no signs of anaemia despite the underlying hookworm infection. The patients also comprised those in whom hookworm was the sole infection and those with hookworm associated with other parasites. Significant differences in the results between each patient subgroup and the controls were analysed using the student t-test. IgA was significantly elevated in patients with anaemia of mild to moderate severity and in patients with hookworm only (P < 0.05) while sIgA was significantly elevated in all subgroups compared to controls (P < 0.05). IgM was significantly elevated in-patients with marked anaemia, in-patients without anaemia and in those with hookworm infection associated with other parasites (P < 0.05). The difference in IgG levels between patients and controls was not significant (P 0.1). C4 was significantly elevated in patients with marked moderate anaemia and those with hookworm only (P < 0.05) while C3 levels were not significantly different in the subgroups compared with controls. These results suggest the possibility of polyclonal B-cell activation by T-independent antigens such as the polysaccharide cuticular antigens of the hookworms and the stimulation of the classical pathway of the complement system.

Adolescent↗

Distribution of hookworm infection in Cameroon.

Prevalence of hookworm infection was measured in Cameroon during a national survey carried out for a schistosomiasis research project. The survey provided a representative sample of the 10-19 year age group for each one of the 49 administrative divisions. Prevalences were low in the Extreme North province with a sahelian climate. Prevalences were high in the provinces with an equatorial climate except for the Centre province which is more developed. Regions with tropical Cameroonian climate, which receive a very heavy rainfall, showed the highest prevalences. Urbanized areas had lower infection rates than rural areas. It should not be assumed that hookworm prevalence is uniformly high throughout a tropical country. Since hookworm distribution shows wide variations, large control programmes should start with a thorough evaluation of the situation.

Adolescent↗

Parasitological, hematologic, and immunologic responses in acute and chronic infections of dogs with Ancylostoma ceylanicum: a model of human hookworm infection.

A model of human hookworm infection has been defined with a strain of Ancylostoma ceylanicum that is known to be infective for humans. In the first experiment, dogs were infected with between 150 and 12,150 filariform larvae and followed up for six weeks. A direct relation was found between the size of infecting dose, fecal egg excretion, intestinal adult worm burden, and worm distribution in the bowel. Dogs with heavy infection developed bloody diarrhea and iron-deficient anemia. In the second experiment, dogs infected with 2,000 larvae excreted ova until autopsy 36 weeks after infection. Normocytic anemia and blood eosinophilia coincided with maximal egg excretion. Transitory lymphocyte stimulation was seen with adult worm antigen. The specific IgM antibody response was transient, but IgG antibodies persisted indefinitely. Marked skin immediate hypersensitivity and Arthus (but no delayed) hypersensitivity reactions were seen to injected larval and adult antigens. Thus, dogs develop both hookworm disease and chronic infections similar to those seen in humans.

Acute Disease↗