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An integrated approach for risk profiling and spatial prediction of Schistosoma mansoni-hookworm coinfection.

Multiple-species parasitic infections are pervasive in the developing world, yet resources for their control are scarce. We present an integrated approach for risk profiling and spatial prediction of coinfection with Schistosoma mansoni and hookworm for western Côte d'Ivoire. Our approach combines demographic, environmental, and socioeconomic data; incorporates them into a geographic information system; and employs spatial statistics. Demographic and socioeconomic data were obtained from education registries and from a questionnaire administered to schoolchildren. Environmental data were derived from remotely sensed satellite images and digitized ground maps. Parasitologic data, obtained from fecal examination by using two different diagnostic approaches, served as the outcome measure. Bayesian variogram models were used to assess risk factors and spatial variation of S. mansoni-hookworm coinfection in relation to demographic, environmental, and socioeconomic variables. Coinfections were found in 680 of 3,578 schoolchildren (19.0%) with complete data records. The prevalence of monoinfections with either hookworm or S. mansoni was 24.3% and 24.1%, respectively. Multinomial Bayesian spatial models showed that age, sex, socioeconomic status, and elevation were good predictors for the spatial distribution of S. mansoni-hookworm coinfection. We conclude that our integrated approach, employing a diversity of data sources, geographic information system and remote sensing technologies, and Bayesian spatial statistics, is a powerful tool for risk profiling and spatial prediction of S. mansoni-hookworm coinfection. More generally, this approach facilitates risk mapping and prediction of other parasite combinations and multiparasitism, and hence can guide integrated disease control programs in resource-constrained settings.

Adolescent↗

Hookworm: not a pre-Columbian pathogen.

It has been asserted that evidence of pre-Columbian hookworm has been found in the Americas, specifically in Peru, Brazil, and Tennessee. However, based on an analysis of the life cycle and morphology of hookworm, the paleopathologic indications for the presence of hookworm infestation in the Americas prior to 1492 are suspect. It is concluded that the material found in the Peruvian mummy is probably pinworms, that the Brazilian and Tennessee materials are probably not hookworm, and, therefore, that hookworm was one of many pathogens brought to the Americas after contact in 1492.

Ancylostomatoidea↗

Epidemiology of iron deficiency anemia in Zanzibari schoolchildren: the importance of hookworms.

Anemia is estimated to affect one-half of school-age children in developing countries. The school years are an opportune time to intervene, and interventions must be based on sound epidemiologic understanding of the problem in this age group. We report on the distribution of iron deficiency and anemia across age, sex, anthropometric indexes, and parasitic infections in a representative sample of 3595 schoolchildren from Pemba Island, Zanzibar. Iron status was assessed by hemoglobin, erythrocyte protoporphyrin (EP), and serum ferritin concentrations from a venous blood sample. Overall, 62.3% of children were anemic (hemoglobin < 110 g/L), and 82.7% of anemia was associated with iron deficiency. The overall prevalence of iron-deficient erythropoiesis (EP > 90 mumol/mol heme) was 48.5%, and the prevalence of exhausted iron stores (serum ferritin < 12 micrograms/L) was 41.3%. In bivariate analyses, iron status was slightly better in girls than in boys, and was better in children aged 7-11 y than in those older or younger. Hemoglobin but not EP or serum ferritin concentrations were lower in stunted children. Infection with malaria, Trichuris trichiura, Ascaris lumbricoides, and hookworms were all associated with worse iron status; the association with hookworms was strongest by far. In multivariate analyses, hookworm infection intensity was the strongest explanatory variable for hemoglobin, EP, and serum ferritin. Sex, malarial parasitemia, A. lumbricoides infection, and stunting were also retained in the multivariate model for hemoglobin. Twenty-five percent of all anemia, 35% of iron deficiency anemia, and 73% of severe anemia were attributable to hookworm infection; < 10% of anemia was attributable to A. lumbricoides, malaria infection, or stunting. We conclude that anthelminthic therapy is an essential component of anemia control in schoolchildren in whom hookworms are endemic, and should be complemented with school-based iron supplementation.

Adolescent↗

Hookworms, malaria and vitamin A deficiency contribute to anemia and iron deficiency among pregnant women in the plains of Nepal.

Anemia and iron deficiency during pregnancy are prevalent in developing countries, but their causes are not always known. We assessed the prevalence and severity of anemia and iron deficiency and their association with helminths, malaria and vitamin A deficiency in a community-based sample of 336 pregnant women in the plains of Nepal. Hemoglobin, erythrocyte protoporphyrin (EP) and serum ferritin were assessed in venous blood samples. Overall, 72.6% of women were anemic (hemoglobin < 110 g/L), 19.9% had moderate to severe anemia (hemoglobin < 90 g/L) and 80.6% had iron deficiency (EP > 70 micromol/mol heme or serum ferritin < 10 microg/L). Eighty-eight percent of cases of anemia were associated with iron deficiency. More than half of the women (54.2%) had a low serum retinol concentration (<1.05 micromol/L), 74.2% were infected with hookworms and 19.8% had Plasmodium vivax malaria parasitemia. Hemoglobin, EP and serum ferritin concentrations were significantly worse and the prevalence of anemia, elevated EP and low serum ferritin was increased with increasing intensity of hookworm infection. Hookworm infection intensity was the strongest predictor of iron status, especially of depleted iron stores. Low serum retinol was most strongly associated with mild anemia, whereas P. vivax malaria and hookworm infection intensity were stronger predictors of moderate to severe anemia. These findings reinforce the need for programs to consider reducing the prevalence of hookworm, malaria infection and vitamin A deficiency where indicated, in addition to providing iron supplements to effectively control anemia.

Adolescent↗

Synergistic associations between hookworm and other helminth species in a rural community in Brazil.

OBJECTIVE: To identify possible synergistic associations of hookworm and other helminths. METHOD: Cross-sectional survey of all households within 10 km2 of Americaninhas, a rural community in Minas Gerais, Brazil. We determined the prevalence and intensity of single and multiple helminth species infection in an age-stratified sample of 1332 individuals from 335 households. RESULTS: Hookworm was the most prevalent helminth infection (68.2%), followed by Ascaris lumbricoides (48.8%) and Schistosoma mansoni (45.3%). Overall, 60.6% of individuals harboured mixed helminth infections. Multivariate analysis indicated significant positive associations for co-infection with hookworm and S. mansoni and for co-infection with hookworm and A. lumbricoides. Co-infections with hookworm and A. lumbricoides resulted in higher egg counts for both, suggesting a synergistic relationship between these species, although, we found important age differences in this relationship. However, the intensity of S. mansoni or A. lumbricoides co-infection did not differ from that of mono-infection. CONCLUSION: These results have implications for the epidemiology, immunology and control of multiple helminth infections. More research is needed to examine the rates of re-infection and immune responses after chemotherapy, and to what extent the effects of polyparasitism are altered by chemotherapy.

Adolescent↗

The short-term impact of albendazole treatment on Oesophagostomum bifurcum and hookworm infections in northern Ghana.

In November-December 2002, stool samples from a random sample of the human population (N = 190) in the Garu area of northern Ghana were checked for intestinal helminths, using a single Kato smear and duplicate coprocultures for each subject. All 190 subjects were subsequently treated with a single, 400-mg dose of albendazole and 146 of them were successfully re-examined 21-28 days post-treatment. Prior to treatment, 75.5% of the Kato smears were found to contain 'hookworm-like' eggs (with a geometric mean egg count among the positives of 578 eggs/g faeces), and the third-stage larvae of Oesophagostomum bifurcum and hookworm were found in the cultures of stools from 34.2% and 77.4% of the subjects, respectively. Among the subjects who had positive Kato smears before treatment, albendazole treatment led to a cure 'rate' of 79.0% and an egg-reduction 'rate' of 73.5%. The results from the coprocultures indicated cure 'rates' of 98.0% for O. bifurcum but only 51.3% for hookworm. Only one subject was still positive for O. bifurcum after treatment. Among those still positive for hookworm after treatment, the larva-reduction 'rate' was 79.8%. The egg-/larva-reduction 'rates' among those with heavy infections prior to treatment were >90%, whether the data analysed came from the Kato smears or the coprocultures. It may be concluded that a single dose of albendazole is very likely to cure an O. bifurcum infection and to reduce greatly the intensity (but not the prevalence) of any hookworm infections.

Albendazole↗

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↗

Relationships of Schistosoma hematobium, hookworm and malarial infections and metrifonate treatment to hemoglobin level in Kenyan school children.

Relationships between hemoglobin level and S. hematobium, hookworm, and malarial infection before and six months after metrifonate treatment were studied in Kenyan primary school children in an area where anemia, S. hematobium and hookworm are common (prevalences 61%, 46%, and 95%, respectively) and malaria is holoendemic. The mean hemoglobin level in children from one school, both with and without S. hematobium infection (n = 250), was significantly lower in children with higher S. hematobium egg counts, heavier hookworm infections, positive Plasmodium slides, and larger spleens. All children with light-moderate S. hematobium infection (1-500 eggs/10 ml adj) in four schools were examined (Exam 1), allocated at random to either placebo (MIP, n = 198) or metrifonate treatment (MIT, n = 202) groups, treated, and examined again six months later (Exam 2). Hemoglobin levels rose significantly in both groups between exams, but the rise in the MIT group was 30% higher than in the MIP group (1.3 vs. 1.0 g/dl, P less than 0.014). The increase in hemoglobin level in the MIT group was significantly and positively correlated with decreases between exams in S. hematobium and hookworm egg counts and with higher malarial parasite counts at Exam 1 (Pearson r's 0.21, 0.20, 0.20, respectively, P less than 0.01). A stepwise multiple regression equation using hemoglobin rise between exams as the dependent variable showed that decreases in S. hematobium and hookworm egg counts were equally important determinants of hemoglobin rise and that malarial parasite count was almost as important as the changes in intensities of the helminth infections. These results show that treatment for S. hematobium with metrifonate can increase hemoglobin levels in children in an area where S. hematobium and anemia are common. They also emphasize the importance of measuring multiple parasitic infections and using multivariate statistical techniques such as multiple regression analysis in order to define the relationships between parasitic infections and morbidity.

Adolescent↗

Hookworm infestation in a 3-month old female.

BACKGROUND: Intestinal helminthiasis is a major cause of morbidity and mortality in infants and children particularly in the tropics and subtropics. This report highlights the possibility of hookworm infestation in infancy. METHOD: A case report of hookworm infestation in a three-month old infant who was managed in the University of Port Harcourt Teaching Hospital, Port Harcourt in May 2001 for failure to thrive and recurrent severe anaemia. RESULT: The patient was admitted in the children's emergency ward with passage of dark watery stools, fever, excessive crying and severe anemia and was transfused twice. Stool microscopy revealed numerous ova of hookworm and she was treated with albendazole. Three days after administration of anti-helminthic, stools became formed with normal colour and temperature was normal. She gained weight before discharge home. CONCLUSION: Hookworm infestation should be suspected as a cause of severe anaemia in infants in communities with a high risk of infestation such as fishing port communities. To the best of my knowledge, symptomatic hookworm infestation in the first year of life has not been previously documented in Nigeria.

Anemia↗

Prevalence of hookworm species in Pondicherry, India.

A study was carried out to find out the hookworm species prevalent in Pondicherry, India, based on the identification of filariform larvae recovered from coproculture of hookworm positive stools. A total of 184 hookworm positive stools were cultured using the Harada-Mori coproculture method. The results of the study for the first time showed both hookworm species, Ancylostoma duodenale (60 cases) and Necator americanus (49 cases) to be present in Pondicherry. The former species was relatively more common than the latter. Three cases were infected with both species of hookworm.

Feces↗

The prevalence of hookworm and of S. haematobium in rural Zambia.

The prevalence of hookworm and of S. haematobium in a representative sample of the rural population of seven provinces of Zambia was assessed during a National Nutrition Status Survey. A total of 7212 people of all age and sex groups were examined for hookworm, of whom 4920 (68%) provided a stool sample and of these 48.6% were positive. Regional figures ranged between 11.4% and 77.1%. No differentiation between species of hookworm was attempted nor was it possible to assess the worm load of the individuals surveyed. Hookworm is highly endemic within the rural areas and this is discussed in relation to its known effects on the general health of the population studied during the survey, and the impact of hookworm infestation on morbidity.

Adolescent↗

Human neonatal infections with hookworms in an endemic area of Southern Nigeria. A possible transmammary route.

Examination of faecal smears of 316 neonates (4-5 weeks old) in a human hookworm endemic area of southern Nigeria showed that 33 (10%) of them were hookworm infected. The majority of the neonatal infections (88%) were due to Ancylostoma duodenale although Necator americanus was the more prevalent hookworm species in the area. The incidence of neonatal infections was pronounced (64%) for mothers who were A. duodenale-positive 5-6 weeks postpartum. A thorough screening of 12.4 litres of colostral milk from all the 316 nursing mothers failed to show the presence of infective hookworm larvae. These results indicate a possibility of a transmammary infection route for the human hookworm A. duodenale.

Ancylostomiasis↗

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↗

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↗

Development and characterization of microsatellite markers for the canine hookworm, Ancylostoma caninum.

Microsatellites are repetitive genomic elements that show high levels of variation and therefore provide excellent tools to study the genetics of eukaryotic organisms. Hookworms are extremely common and important nematode parasites of humans and animals, causing potentially serious disease morbidity. Control of hookworms in dogs is achieved by frequent treatment with anthelmintics, and in humans, anthelmintics are frequently administered in a mass-treatment community-wide approach. Understanding the population genetics of hookworms has important implications for studies on the development and spread of drug resistance. We investigated the genome of Ancylostoma caninum for microsatellites by developing and then screening an enriched genomic library as well as by data mining published sequences of a whole genome shotgun library. Investigations revealed a high abundance of trinucleotide repeats. Dinucleotide repeats were characterized by a high number of AT, GA, and GT repeats. After testing and optimization of 68 markers, a panel of 34 polymorphic microsatellite markers were selected. Microsatellite analysis of hookworm isolates revealed a high degree of polymorphism, which was not influenced by the length of the repeats. This panel of microsatellite markers makes it possible to pursue investigations on the population genetics of A. caninum. Furthermore, a number of the markers demonstrated suitability for analysis of the human hookworm species Necator americanus and A. duodenale.

Ancylostoma↗

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↗

Identification of a DAF-7 ortholog from the hookworm Ancylostoma caninum.

Infective hookworm L3 encounter a host specific signal during invasion that re-activates suspended developmental pathways. Response to this cue is critical for the successful infection and completion of the life cycle in the host. In the free-living nematode Caenorhabditis elegans, recovery from the developmentally arrested dauer stage in response to environmental cues is analogous to the resumption of development in invading hookworm L3. Transforming growth factor beta (TGF-beta) and insulin-like signalling pathways mediate dauer formation and recovery. An insulin-like signalling pathway mediates L3 activation in hookworms. To determine the role of TGF-beta signalling in hookworm infection, an ortholog of the C. elegans TGF-beta signalling molecule daf-7 was cloned and characterised. Sequence from a hookworm expressed sequence tag was used to design specific primers for PCR amplification of Ac-daf-7 from Ancylostoma caninum infective L3 cDNA. Amplicons from the 5' and 3' ends were cloned, sequenced, and combined to create a full-length composite Ac-daf-7 cDNA sequence. The 1,634 nucleotide cDNA encoded a 355 amino acid open reading frame with significant homology to Ce-DAF-7 and other TGF-beta signalling molecules. The deduced amino acid sequence contained seven conserved cysteines characteristic of TGF-beta family members, as well as two additional conserved cysteines found in members of the TGF-beta/activin subfamily. Ac-DAF-7 contains a characteristic C-terminal ligand domain that is predicted to be released from a propeptide by proteolytic cleavage at a tetrabasic cleavage site. Ac-daf-7 mRNA was strongly detected by reverse transcriptase PCR in L3 and serum stimulated L3 cDNA, and weakly in cDNA from L1 and adult life cycle stages. Antiserum against Escherichia coli expressed recombinant Ac-DAF-7 detected the mature protein in L3 and adult soluble extracts, but not in excretory/secretory products from serum stimulated L3 or adults. Increased expression in arrested L3 stages suggests that Ac-daf-7 is important for developmental arrest.

Amino Acid Sequence↗

Failure of pyrantel in treatment of human hookworm infections (Ancylostoma duodenale) in the Kimberley region of north west Australia.

A survey of 108 individuals from a coastal Aboriginal community in north Western Australia revealed that two species of gastrointestinal protozoan parasites (Giardia duodenalis--39.8%, Entamoeba coli--40.7%) and five gastrointestinal helminths (Hymenolepis nana--54.6%, Hookworm [Ancylostoma duodenale]--30.6%, Enterobius vermicularis--6.5%, Trichuris trichiura--2.8%, Strongyloides stercoralis 1.9%) were present. A total of 29 individuals infected with hookworm were offered treatment with either pyrantel pamoate at a single dose rate of 10 mg/kg body weight or albendazole (single 400 mg dose). Seven days after treatment stool samples were examined. Pyrantel had no significant effect against hookworm. In contrast, albendazole cleared hookworm infections completely and reduced the prevalence of Giardia. The former result suggests that locally A. duodenale is resistant to pyrantel and despite its relatively low cost and wide availability, should not be considered a drug of choice at this dose rate in the treatment of hookworm infections (A. duodenale) in endemic regions.

Adolescent↗