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Hookworm antigens: the potential for vaccination.

Hookworms rank with Ascaris as the most prevalent soil-transmitted helminths of man. Up to 1000 million people may be infected. Not all suffer the life-threatening anaemia that reflects heavy burdens of hookworms, but even mild iron-deficiency anaemia due to hookworms can lead to intellectual and growth retardation - especially among infected children. Health education, mass chemotherapy and the sanitary disposal of faeces have been the traditional mainstays of hookworm control, but more recently chemotherapy targeted only to heavily infected individuals who appear predisposed to hookworm anaemia has emerged as a realistic alternative. Ultimately, however, knowledge of the molecular immunology of hookworm infection may provide the basis for rational vaccine development. Although the evidence for acquired immunity to hookworms in man is not strong, work is now underway to identify and to characterize antigens from third and fourth larval stages and adults of Necator americanus and species of Ancylostoma (Table 1). As this article shows, the work provides real promise for improved immunodiagnosis and possible vaccination.

Journal Article↗

A new approach to morbidity risk assessment in hookworm endemic communities.

The relationship between paired hookworm prevalence and mean intensity of infection data from geographically defined communities was examined. The results show that, in spite of major socio-economic and environmental differences between communities, the relationship is consistent and non-linear. A generalized value of k (the exponent of the negative binomial distribution) for hookworms was estimated to be 0.34, which is consonant with previous estimates from cross-sectional data. Maximum likelihood analysis indicates that the severity of hookworm aggregation in humans has an inverse relationship to mean worm burden which is less marked than for Ascaris lumbricoides. A simple model, based on published estimates of hookworm burdens associated with hookworm anaemia, was used to predict prevalence of morbidity from prevalence of infection data for Tanzania, Kenya and Zambia. Predictions correspond to the observation that hookworm anaemia is highly focal, and largely coastal, in distribution. These analyses suggest that locality-targeting of chemotherapy is particularly appropriate for the control of hookworm morbidity.

Ancylostomiasis↗

Molecular characterization of Ancylostoma inhibitors of coagulation factor Xa. Hookworm anticoagulant activity in vitro predicts parasite bloodfeeding in vivo.

Bloodfeeding hookworms, which currently infect over a billion people in the developing world, are a leading cause of gastrointestinal hemorrhage and iron deficiency anemia. The major anticoagulant inhibitor of coagulation factor Xa has been identified from the hookworm parasite Ancylostoma ceylanicum using reverse transcription PCR and 3'-rapid amplification of cDNA ends. This is the first anticoagulant cloned from a hookworm species for which humans are recognized permissive hosts. Despite approximately 50% amino acid similarity, A. ceylanicum anticoagulant peptide 1 (AceAP1) is both immunologically and mechanistically distinct from AcAP5, its homologue isolated from the dog hookworm Ancylostoma caninum. Studies using plasma clotting times and single stage chromogenic assays of factor Xa activity have demonstrated that the recombinant AceAP1 protein is substantially less potent than AcAP5 and that soluble whole worm protein extracts of adult A. ceylanicum possess less anticoagulant activity than extracts of A. caninum. These values correlate with previously reported differences in bloodfeeding capabilities between these two species of hookworm, suggesting that factor Xa inhibitory activity is predictive of hookworm bloodfeeding capabilities in vivo. These fundamental differences in the mechanism of action and immunoreactivity of the major anticoagulant virulence factors from related Ancylostoma hookworm species may have significant implications for human vaccine development.

Amino Acid Sequence↗

Hookworm disease: host-pathogen biology.

The hallmark of hookworm infection, a common helminthic disease, is iron deficiency anemia. The development of anemia is dependent on the intensity of infection, the species of hookworm, and the ability of the host to resist infection and to maintain adequate stores of iron. When conditions are appropriate, the incidence of anemia caused by hookworm is high and has a significant economic impact since it results in a reduction of worker productivity. Loss of blood is caused by direct ingestion of red cells and by tissue trauma produced by worm attachment and feeding. This focal trauma may involve multiple villi and is characterized by local hemorrhage, tissue cytolysis, and neutrophilic response. Although focal intestinal lesions are apparent, their significance is questionable since diffuse mucosal changes are absent in intestinal biopsies of patients with heavy hookworm infection. Short-range control measures protecting against hookworm infection have not succeeded. Development of a vaccine against hookworm infection in humans is problematic since functional protective immunity in humans has not yet been demonstrated and no suitable animal model of hookworm infection in humans is available. At present, the most effective method of intervention appears to be supplementation of food staples with iron.

Ancylostomiasis↗

Hookworm control as a strategy to prevent iron deficiency.

The hookworms Necator americanus and Ancylostoma duodenale infect approximately 1 billion people worldwide. The prevalence of hookworm infection increases with age in children, typically reaching a plateau in late adolescence, whereas the intensity of infection may continue to increase throughout adulthood. Hookworms cause intestinal blood loss in amounts proportional to the number of adult worms in the gut. The relationship between hookworm infection intensity and hemoglobin concentration is evident in epidemiologic studies, but may be apparent only above a threshold worm burden that is related to the iron stores of the population. Current hookworm control efforts are focused on reducing infection load and transmission potential through periodic anthelminthic chemotherapy. Several controlled trials have demonstrated a positive impact of anthelminthic treatment on hemoglobin levels, with best results obtained in settings where iron intakes were also increased. Evidence suggests that anthelminthic programs will have modest impacts on iron deficiency anemia in the short term, with greater impacts on more severe anemia. Hookworms are an important cause of anemia in women, who are often overlooked by current helminth control programs. Current WHO recommendations for use of anthelminthics in schoolchildren and women are reviewed. There is a need to clarify whether hookworms are an important etiology of iron deficiency anemia in preschool children.

Adolescent↗

Epidemiology of Necator americanus hookworm infections in Xiulongkan Village, Hainan Province, China: high prevalence and intensity among middle-aged and elderly residents.

Hookworm is highly endemic to Hainan Province, an island located in the South China Sea. To investigate the prevalence and intensity of infection in the area, the village of Xiulongkan was surveyed between April and July 1998. A cross-sectional study was conducted in which fecal samples of 80% of the village residents (631 individuals) were tested for the presence of helminth eggs. Hookworm was the predominant intestinal helminth in Xiulongkan, where it was determined that 60% of those tested were infected. Necator americanus was the predominant species of hookworm in this population. The prevalence of hookworm increased with age, and then leveled to a plateau for ages 41 yr and up. This observation was in contrast to infections with Ascaris lumbricoides, where the highest prevalences occurred among school-aged children. Women had a significantly higher prevalence of hookworm than men and this difference emerged in early adulthood. The intensity of hookworm infection also significantly increased with age, with the highest intensity infections occurring among middle-aged and elderly residents. Females were more likely to have moderate or heavy infections, whereas males were more likely to have light infections. The rates of hookworm transmission are particularly high among the middle-aged and elderly residents of Xiulongkan.

Adolescent↗

[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↗

Infection with Schistosoma mansoni correlates with altered immune responses to Ascaris lumbricoides and hookworm.

Studies were performed on humoral and cellular immune responses of patients from areas in Brazil endemic for hookworm and Ascaris lumbricoides, and either endemic or non-endemic for Schistosoma mansoni. Humoral and cellular responses were evaluated by enzyme-linked immunosorbant assay (ELISA) and peripheral blood mononuclear cell (PBMC) proliferation assays against larval hookworm antigens, A. lumbricoides egg antigens, and soluble egg antigens (SEA) or soluble whole adult antigenic preparation (SWAP) from S. mansoni. Patients from S. mansoni-endemic areas, who currently had only hookworm or Ascaris infections, expressed lower humoral and cellular responses to hookworm or Ascaris antigens, respectively, than did their counterparts from areas not endemic for S. mansoni. Individuals from S. mansoni endemic area, although without detectable S. mansoni infection, do mount humoral and cellular responses to SEA and SWAP. This group of individuals has been probably in contact with S. mansoni antigens, since the groups harboring A. lumbricoides or hookworm infections from non-S. mansoni endemic areas do not have detectable anti-S. mansoni responses. PBMC proliferative responses discriminated well between patients with active hookworm infections versus ascariasis, if they were from areas not endemic for S. mansoni.

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↗

The epidemiology of hookworm infection and its contribution to anaemia among pre-school children on the Kenyan coast.

Intestinal nematode infections are recognized as a major public health problem, and helminth control is currently being directed towards school-aged children who are known to harbour the heaviest infections and are most likely to suffer from associated morbidity. However, few data are available for the epidemiology of intestinal nematodes in pre-school children in Africa, and the contribution of hookworm infection to the aetiology and severity of anaemia among pre-school children remains poorly understood. This paper investigates the epidemiology of parasitic infections in 460 pre-school children who were part of a larger case-control study of severe malaria in Kilifi on the Kenyan coast. Almost one-third (28.7%) were infected with hookworm, 20.2% with Ascaris lumbricoides and 15.0% with Trichuris trichiura. Infection prevalence of each species rose with age, and the prevalence of heavy infection with hookworm and mean intensity of hookworm were markedly age-dependent. One-third (34.3%) of children had malaria. Overall, 76.3% of children were anaemic (haemoglobin < 110 g/L), with the prevalence decreasing with age. Anaemia was significantly worst in children with heavy hookworm infection (> 200 eggs per gram). This relationship held for all ages, both sexes, and was independent of socioeconomic factors. The application of attributable morbidity methods confirmed the contribution of hookworm infection to anaemia.

Anemia↗

Public health policy paradoxes: science and politics in the Rockefeller Foundation's hookworm campaign in Mexico in the 1920s.

The origins of US international health endeavors are intertwined with the Progressive Era's faith in science as arbiter of humankind's secular problems. No agency better exemplifies the period's confidence in science than the Rockefeller Foundation's International Health Board (IHB), which set out to export the new public health theory and practice around the world. An examination of the IHB's hookworm program in Mexico in the 1920s demonstrates that, notwithstanding the Rockefeller Foundation's (RF) self-conscious commitment to scientific neutrality, its programs continuously engaged political criteria, exhibiting the competition, coexistence, and inseparability of the worlds of science, politics, and international health policy. Analysis of the program's quotidian decisions and larger strategies further reveals the protean quality of RF science-politics, which enabled responses to parochial and broadly-conceived needs at multiple levels. In the focus on hookworm, the selection of campaign sites, hookworm diagnosis methods, treatment procedures, definition of cure, and the assignment of responsibility for prevention, scientific and political considerations were inextricably bound. The science-politics paradox was molded by the hookworm program's constituencies in Mexico, including political leaders, health bureaucrats, physicians, business interests, public health workers, peasants, and Rockefeller officers. The multiple, often contradictory, roles of the RF's hookworm campaign are characteristic of the policy paradoxes that emerge when science is summoned to drive policy. In Mexico the campaign served as a policy cauldron through which new knowledge could be demonstrated applicable to social and political problems on many levels. The repeated pledge of scientific neutrality belied the hookworm program's inherent aim of persuading government officials, the medical community, business interests, and the populace of the value of investing in public health as a means to improve social conditions, further a medical model of health and sickness, increase economic productivity, and promote good relations between the US and Mexico.

Culture↗

The effect of soil type and climate on hookworm (Necator americanus) distribution in KwaZulu-Natal, South Africa.

We investigated environmental factors influencing the distribution of hookworm infection in KwaZulu-Natal, South Africa. Prevalence data were sourced from previous studies and additional surveys carried out to supplement the database. When geo-referenced the data revealed that higher prevalences are limited to areas below 150 m above sea level, and low prevalences to areas above this altitude. Using univariate analysis we investigated the differences in environmental factors in the two areas. The relationship between hookworm prevalence, altitude and climate-derived variables was assessed using Pearson correlation coefficient, and that of soil type using the t-test. Multivariate analysis was used to determine environmental factors that combine best to provide favourable conditions for hookworm distribution. The results revealed that areas 150 m above sea level, i.e. inland, supported low mean hookworm prevalences (x = 6, n = 21), and were characterized by soils with a clay content of more than 45%, variable temperatures and moderate rainfall. Hookworm prevalence also decreased southwards as temperatures became slightly cooler, rainfall remained more-or-less constant and the coastal plain narrowed. In the multivariate model prevalence was most significantly correlated with the mean daily minimum temperature for January followed by the mean number of rainy days for January. This indicates the importance of summer conditions in the transmission of hookworm infection in KwaZulu-Natal and suggests that transmission may be seasonal.

Adolescent↗

Experimental approaches to the development of a recombinant hookworm vaccine.

Hookworm infection is a major parasitic cause of morbidity in the developing nations of the tropics. Development of a genetically engineered vaccine would be a useful tool in the control of this infection in highly endemic areas. Recombinant polypeptides belonging to the Ancylostoma secreted protein (ASP)-1 family have shown promise for reducing hookworm burdens after larval challenge infections in mice. Typically, these polypeptides are expressed in Escherichia coli and administered as an alum precipitate. Vaccine protection is antibody dependent. It is anticipated that a cocktail of different recombinant hookworm antigens may be required in order to effectively prevent heavy hookworm infections and disease. The progress of this work has been hampered by the absence of both a convenient laboratory animal with which to study hookworm infections resembling human infection, as well as the lack of easy availability of native hookworm antigens. In addition, useful human serologic correlates of antihookworm immunity are still poorly defined.

Ancylostoma↗

Evaluation of the skin test for hookworm as an epidemiological tool.

The usefulness of a skin test with larval Necator americanus antigen for assessment of hookworm prevalence was evaluated in an endemic area of Costa Rica. In comparison with standard coprologic techniques employed to survey the population, the skin test detected 83% of infections, showing a fairly satisfactory sensitivity. The overall specificity of the test was 50%, i.e., random. No correlation was found between skin reactivity and hookworm burden. The sensitivity of the test increased moderately with age, but its specificity decreased significantly at the same time. False positive reactions were more numerous among persons formerly infected with hookworm who had been negative for as long as 5 years. There was an indication of cross reactivity with intestinal nematodes other than hookworm. The test was used to detect hookworm infected persons in the community for selective treatment, in comparison with mass treatment of all the people in another village. The selective administration of an anthelminthic drug to only skin test positive persons did not achieve the same drop in community hookworm prevalence as did the indiscriminate treatment of the whole population.

Adolescent↗

The detection of antibodies to hookworm larva in patients by immunofluorescence: a preliminary report.

Using the fluorescent antibody technique 84% of patients with severe hookworm infection and 74% of Nigerian blood donors have detecable antibodies that react with surface antigen of hookworm larvae. On the other hand only 24% of Nigerian medical students and 20% of Caucasians (Canadians) have such antibodies in their sera. It is suggested that while the results of tests on students may be due to the relatively infrequent contact with hookworm the antibody positivity in the Caucasians may be due to cross reaction with other related helminths. The titre of antibody produced in the hookworm infected patients was similar to that of the blood donors but differed from other groups. Lower positivity rates were observed with further dilution of sera in the hookworm infected patients. This may be due to their relative incapacity to produce potent hookworm antibody. Further work on this aspect is required as well as improvement of the specificity of the technique.

Antibodies↗

Hookworm infection among the Melka Sedi banana plantation residents, middle Awash Valley, Ethiopia.

A study of intestinal parasites was done among the people who lived within the banana plantation zone of the Melka Sedi Agricultural Enterprise, Awash Valley, Ethiopia in April 1987. The methods of parasite detection were the Ritchie formal ether and the charcoal culture method for hookworm larvae species identification. From the total 633 population, 311 were examined at random of whom 60.8% were positive for one or more intestinal parasites. Eight parasites were encountered, Ascaris lumbricoides in 1.3%, Trichuris trichiura in 6.4%, Strongyloides stercoralis in 3.9%, hookworm in 53.1%, Taenia sp. in 3.5%, Schistosoma mansoni in 1.9%, Entamoeba histolytica in 0.6% and Hymenolepis sp. in 0.6%. Prevalence of hookworm infection was significantly higher than that of any of the other parasites (p less than 0.001). In the hookworm infected individuals there were more males than females, and the 25 to 34 year age group had significantly higher infection rates (p less than 0.05). The majority of those with hookworm were banana plantation workers. This communication emphasizes the basic guidelines for control and prevention of hookworm and other related faecal/soil-borne infections in this and similar agricultural settings.

Adolescent↗

[Hookworm disease. A differential diagnosis in iron deficiency anemia].

Hookworms are among the most widespread of human parasites and occur all over the tropics and subtropics. They are bloodsucking roundworms that inhabit the duodenum and jejunum. Usually the infection is mild (hookworm carrier state), but sometimes the infection is heavy and results in anaemia and/or hypoproteinemia (hookworm disease). Hookworms are occasionally imported to Norway by immigrants. This paper describes two cases of severe and life-threatening hookworm disease treated in our hospital. The first patient was a Pakistani woman born in 1929 who on admission was hypovolemic with severe hypochromic anaemia (haemoglobin 3.6 g/100 ml). The second patient was a Bolivian refugee born in 1946 with a similar clinical picture (haemoglobin 3.3 g/100 ml). Both patients were treated with blood transfusions followed by mebendazol and iron substitution. The article also reviews the current literature on the epidemiology, pathogenesis and therapy of hookworm infection.

Aged↗

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↗