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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↗

Vaccination with recombinant aspartic hemoglobinase reduces parasite load and blood loss after hookworm infection in dogs.

BACKGROUND: Hookworms infect 730 million people in developing countries where they are a leading cause of intestinal blood loss and iron-deficiency anemia. At the site of attachment to the host, adult hookworms ingest blood and lyse the erythrocytes to release hemoglobin. The parasites subsequently digest hemoglobin in their intestines using a cascade of proteolysis that begins with the Ancylostoma caninum aspartic protease 1, APR-1. METHODS AND FINDINGS: We show that vaccination of dogs with recombinant Ac-APR-1 induced antibody and cellular responses and resulted in significantly reduced hookworm burdens (p = 0.056) and fecal egg counts (p = 0.018) in vaccinated dogs compared to control dogs after challenge with infective larvae of A. caninum. Most importantly, vaccinated dogs were protected against blood loss (p = 0.049) and most did not develop anemia, the major pathologic sequela of hookworm disease. IgG from vaccinated animals decreased the catalytic activity of the recombinant enzyme in vitro and the antibody bound in situ to the intestines of worms recovered from vaccinated dogs, implying that the vaccine interferes with the parasite's ability to digest blood. CONCLUSION: To the best of our knowledge, this is the first report of a recombinant vaccine from a hematophagous parasite that significantly reduces both parasite load and blood loss, and it supports the development of APR-1 as a human hookworm vaccine.

Amino Acid Sequence↗

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↗

Hookworm infection: new developments and prospects for control.

PURPOSE OF REVIEW: Hookworm infection remains a major health burden in developing countries. Successful control will likely be achieved through continued advances in our understanding of the epidemiology, molecular biology and immunopathogenesis of hookworm infection. This review summarizes recent advances in each of these fields, and discusses ongoing efforts to develop vaccines against hookworm anemia and growth delay. RECENT DEVELOPMENTS: Revised estimates indicate that hookworms afflict over 700 million persons in tropical and subtropical regions. Prevalence and intensity often vary considerably at both the regional and local levels, and may be influenced by climate, soil composition, education, and socioeconomic status. Immunoepidemiological studies suggest that hookworm infection likely induces a complex mixture of host-protective and pathological immune responses. There has been substantial progress in elucidating the molecular pathogenesis of hookworm disease, primarily through the identification of a number of parasite virulence factors. Mass chemotherapy remains a mainstay of hookworm control strategies although continued use of benzimidazole anthelminthics is perhaps contributing to the development of anthelminthic resistance. Consequently, there remains a need for innovative approaches, including the development of vaccines and new chemotherapeutic agents, in order to provide effective global control of hookworm disease. SUMMARY: Hookworm infection and disease is a significant threat to global health. Recent advances, particularly those at the molecular level, have provided a wealth of opportunities to better understand pathogenesis. This will likely allow for the development of novel measures such as vaccines to complement existing control methods.

Ancylostoma↗

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↗

Human hookworm infection in the 21st century.

The scientific study of human hookworm infection began at the dawn of the twentieth century. In recent years, there have been dramatic improvements in our understanding of many aspects of this globally widespread parasite. This chapter reviews recent advances in our understanding in the biology, immunology, epidemiology, public health significance and control of hookworm, and to look forward to the study of this important parasite in the 21st century. Advances in molecular biology has lead to the identification of a variety of new molecules from hookworms, which have importance either in the molecular pathogenesis of hookworm infection or in the host-parasite relationship; some are also promising vaccine targets. At present, relatively little is known about the immune responses to hookworm infection, although it has recently been speculated that hookworm and other helminths may modulate specific immune responses to other pathogens and vaccines. Our epidemiological understanding of hookworm has improved through the development of mathematical models of transmission dynamics, which coupled with decades of field research across multiple epidemiological settings, have shown that certain population characteristics can now be recognised as common to the epidemiology, population biology and control of hookworm and other helminth species. Recent recognition of the subtle, but significant, impact of hookworm on health and education, together with the simplicity, safety, low cost and efficacy of chemotherapy has spurred international efforts to control the morbidity due to infection. Large-scale treatment programmes are currently underway, ideally supported by health education and integrated with the provision of improved water and sanitation. There are also on-going efforts to develop novel anthelmintic drugs and anti-hookworm vaccines.

Ancylostomatoidea↗

Prevalence of hookworm infection and its association with low haematocrit among resettlers in Gambela, Ethiopia.

A cross-sectional survey of hookworm infection and haematocrit (HCT) levels was conducted in 7 resettled villages and 3 indigenous villages on sample populations selected by two-stage random sampling. Of 614 resettled persons and 187 indigenous persons, 65.5% and 60.4% respectively were infected with hookworm. Mean haematocrits for 664 resettled and 222 indigenous persons were 33.1% and 35.2%, respectively. A significant association (odds ratio = 2.65) was found between low haematocrit level (below the median for the sample population) and hookworm infection in the resettled population. Suggestions are made on the need for further studies and intervention programmes.

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↗

Hookworm infections in human and laboratory animals--differences and similarities in immune responses.

Hookworm infection is one of the most important parasitic infections of humans. About 740 million people are infected with Ancylostoma duodenale and Necator americanus in the tropics and subtropics. Unlike most other human helminth infections, neither age nor exposure-related immunity develops in the majority of infected people. This review presents the contemporary knowledge concerning the immune response to this complex eukaryotic parasite, recent findings on the human cellular immune responses to hookworms, as well as mechanisms used by the parasite to modulate the immune response in its favor. Also immunological responses in animal models of hookworm infection are presented. Animals in contrast to humans seem to easily deal with hookworm infections and gain protection during re-exposure.

Ancylostomatoidea↗

Efficacy of DEC against Ascaris and hookworm infections in schoolchildren.

Diethylcarbamazine (DEC) is an important drug for treatment and control of lymphatic filariasis. To assess its possible effect on Ascaris and hookworm infections, we conducted a double-blind two-armed study with children in Tanzania. Twenty six Ascaris-infected children were given a single dose of DEC (6 mg/kg body weight) and 25 were given a placebo. Twenty children in the treatment group and eighteen controls were also infected with hookworms. One month after treatment the geometric mean intensity (GMI) of Ascaris egg output was reduced by 60.2% in the treatment group; two children (7.7%) had stopped excreting Ascaris eggs, and some Ascaris worms were also expelled. In hookworm-infected children in the treatment group, the geometric mean intensity of hookworm egg output was reduced by 6.7% 1 month after treatment. Neither for Ascaris nor for hookworm, however, was the observed reduction in egg output at 1 month after treatment statistically significant. The treatment efficacy of a single dose of DEC (6 mg/kg) in these infections therefore was low.

Adolescent↗

Diagnosis of Strongyloides and hookworm infections: comparison of faecal and duodenal fluid microscopy.

Faecal microscopical diagnosis of Strongyloides and hookworm infections is insensitive. We have therefore compared duodenal fluid and faecal microscopy for detection of these parasites in a group of 292 patients being investigated for gastrointestinal symptoms who were examined by both techniques. Thirty-three of these patients (8%) were infected with Strongyloides stercoralis and 88 (30%) had hookworm infections. Microscopical examination of up to 3 faecal specimens detected only 33% and 65% of patients with Strongyloides and hookworm infections, respectively. Microscopical examination of a single specimen of duodenal fluid was more sensitive for detection of strongyloidiasis, identifying 76% of patients; the parasite was found exclusively in duodenal fluid (and not in faeces) in 67% of patients. For hookworm, the diagnostic sensitivity was similar with both techniques but duodenal fluid microscopy detected some patients (35%) who had not been identified by faecal microscopy. This study confirms previous work indicating the insensitivity of faecal microscopy in these infections and emphasizes the need to consider routine examination of duodenal fluid to exclude chronic strongyloidiasis. This may have particular relevance for south-east Asian war veterans and immunocompromised patients.

Ancylostomatoidea↗

Some epidemiological aspects of hookworm infection among the rural population of Bali, Indonesia.

Stool examination using direct smear method, Kato-Katz thick smear technique and modified Harada Mori test tube cultivation method were done on 2,331 people among the rural population of Bali. The serum ferritin was examined by ELISA technique and hemoglobin concentration by cyanmethemoglobin technique. Overall prevalence of hookworm infection was 24.02% with heterogeneity in local prevalences. The highest prevalence was found in wet highland area (46.3%), followed by wet lowland (27.7%), dry highland (14.2%) and dry lowland (10.9%). The majority of hookworm infection cases were associated with Ascaris and Trichuris infections. Most of the hookworm infections (73.3%) were light/very light in intensity with a mean EPG of 619. The prevalence and intensity of infection were increasing with age, and the age-prevalence and age-intensity curves were slightly convex. There was no significant difference of prevalence or intensity of infection between males and females. The condition and humidity of soil found to be an important determinant for prevalence of hook-worm infection. The frequency distribution of the intensity of hookworm infection showed an over-dispersed distribution pattern with 10% of people harboring more than 63% of parasite burden as measured by EPG. The prevalence of anemia was higher, but not statistically significant, in hookworm infected persons compared with people without infection. But this study failed to show a significant correlation between intensity of infection with hemoglobin level. There was a significant correlation between serum ferritin level with intensity of infection.

Age Factors↗

Hookworm infections of schoolchildren in southern Thailand.

A study of hookworm infections of schoolchildren was conducted in Nakhon Si Thammarat Province, southern Thailand. Of the 2,940 hookworms that were recovered from the children, almost all (99.9%), were Necator americanus, only three (0.1%) were identified as Ancylostoma duodenale, and all were female worms. An estimation of the worm burden of and the worm expulsion from the schoolchildren indicated there were 17 cases of light intensity hookworm infection. Fifteen cases (88.2%) expelled worms in numbers that corresponded with the worm burden that was estimated from the number of eggs per gram of feces. Two cases (11.8%) expelled more worms than predicted. In 16 moderate intensity cases, five (31.3%) expelled worms in a quantity that corresponding with the estimated worm burden. Eleven cases (68.7%) expelled fewer worms than predicted. All cases of heavy intensity infection expelled fewer worms than predicted.

Animals↗

The prevalence of hookworm infection, iron deficiency and anaemia in an aboriginal community in north-west Australia.

OBJECTIVE: To determine the prevalence of hookworm infections, iron deficiency and anaemia in an Aboriginal community in the north of Western Australia. DESIGN AND SETTING: A cross-sectional survey conducted in 1992, examining faecal specimens and blood samples from Aboriginals and non-Aboriginals in a remote coastal community in the north of Western Australia. PARTICIPANTS: All those living in the community at the time of the survey. MAIN OUTCOME MEASURES: Parasite status and haematological values for haemoglobin, serum iron, ferritin, transferrin and mean red cell volume. RESULTS: Infections with hookworm were present throughout the Aboriginal population (77%; n = 243), with the highest prevalence in children aged 5-14 years (93%; n = 74). Hookworm was not detected in non-Aboriginals (n = 24). Iron deficiency was common throughout the Aboriginal population, especially in children aged 5-14 years (79%; n = 68) and women aged over 14 years (72%; n = 65). Anaemia was highly prevalent among Aboriginal children aged 5-14 years (84% in hookworm-positive children, 75% in hookworm-negative) and women aged over 14 years (63% in hookworm-positive women, 31% in hookworm-negative). Aboriginals over 14 years of age who had hookworm (n = 82) had significantly lower levels of haemoglobin, serum iron and serum ferritin, a lower mean red cell volume and significantly higher transferrin levels than uninfected Aboriginals (n = 38) and non-Aboriginals (n = 19) in the same age group. Hookworm infections were associated with anaemia (P < 0.01) and iron deficiency (P < 0.01) in people over 14 years of age. The species of hookworm, determined after examining 13 larval cultures and two adult worms, was found to be Ancylostoma duodenale. CONCLUSION: Infections with A. duodenale are endemic in Aboriginals in this community, and are likely to contribute to the high prevalence of iron deficiency and anaemia observed in the Aboriginal population, particularly in children and women.

Adolescent↗