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Lead poisoning and hookworm infection as multiple factors in anaemia.

A retrospective study was carried out in a rural area of north-eastern Brazil, to search for interactions between biological and chemical agents present in the environment as causes of anaemia. A lead smelter situated in a hookworm endemic area provided the opportunity to look at the effect of this double exposure in relation to laboratory defined anaemia, by comparing the odds ratios in different subgroups of 109 "cases" and 107 "controls". The subgroup with both hookworm infection and chronic lead poisoning--measured by the concentration of delta-ALA excreted in urine--had an odds ratio of developing anaemia five times greater than individuals with neither. Although a synergistic effect could not be demonstrated, the additive effect of the two conditions placed this group in a higher risk category.

Anemia↗

Estimation of hookworm intensity by anthelmintic expulsion in primary schoolchildren in south India.

A study was carried out between March 1990 and February 1991 to determine the prevalence and intensity of hookworm infection in 151 primary schoolchildren, aged 6-12 years, in Jalaripet, a slum area in South India predominantly inhabited by fishermen. Pre-treatment stool samples were processed by a modified formalin-ethyl acetate sedimentation technique to determine ova counts. All children were treated with pyrantel pamoate and post-chemotherapy stools were collected over 48 h to recover expelled worms. The overall prevalence of hookworm infection was 45% and the mean egg count was 192 eggs/g. The mean worm burden was 1.25 worms/child. The influence of host factors such as age and sex, environmental factors and behavioural factors on the intensity of egg output and worm burden was investigated.

Age Factors↗

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↗

Development of the egg hatch assay for detection of anthelminthic resistance in human hookworms.

Evidence of development and rapid spread of anthelminthic resistance in veterinary nematodes raises concern that the increasingly frequent treatments used in chemotherapy-based programmes to control human soil-transmitted helminths may select resistant worms. The aim of this study was to adapt, refine, and evaluate the Egg Hatch Assay (EHA) test, which has been used for veterinary nematodes, for field testing of benzimidazole (BZ) susceptibility/resistance in human hookworms. A second objective was to use this EHA to assess whether a population of worms resistant to mebendazole (MBZ) has built up in a sub-population of frequently treated children in Pemba Island. Stools from 470 school children enrolled in the first (Standard 1) and in the fifth (Standard 5) class were examined at baseline and at 21 days after treatment with 500 mg MBZ or placebo tablets. Standard 1 children had never received any MBZ treatment whilst Standard 5 children had received a total of 13 rounds of treatment. The EHA, involving culture of purified eggs with increasing drug concentrations showed that, for thiabendazole (TBZ), the mean ED(50)s (concentrations required to prevent 50% of the viable eggs from hatching) for all children at baseline were 0.079 microg/ml at 48h and 0.120 microg/ml at 72h (P<0.001). For MBZ, the mean ED(50)s for all children at baseline were 0.895 microg/ml at 48h and 1.50 microg/ml at 72h (P<0.001). For TBZ and for MBZ the ED(50) from Standard 1 were similar to those from Standard 5 children both at 48 and at 72h. At the follow-up for TBZ and for MBZ, there was no significant difference between the ED(50) from children who had received MBZ and children treated with placebo. In Pemba, TBZ ED(50) values of children non-exposed (Standard 1) and of children exposed (Standard 5) to MBZ treatment, and data from children treated with MBZ and placebo indicate that a drug-resistant worm population has not built up within treated individuals, and that periodic treatment has not yet selected for widespread BZ resistance, at least at the threshold detectable by the EHA in this study. However, ED(50) values for strains isolated from Mafia island, an area never exposed to BZ treatment were lower than for Pemba, suggesting lowered sensitivity of hookworm eggs recovered from Pembian children towards BZ.

Ancylostomatoidea↗

High risk of hookworm infection among wastewater farmers in Pakistan.

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

Adolescent↗

The human environment, occupation, and possible water-borne transmission of the human hookworm, Necator americanus, in endemic coastal communities of the Niger Delta, Nigeria.

A 15-month longitudinal study was carried out in four riverine communities of the Niger Delta to ascertain the impact of the environment and occupation on the transmission and infection pattern of the human hookworm Necator americanus. A total of 925 (50.10%) individuals were found to be infected. Male and female infection rates were 54.26% and 47.96% respectively. The difference was statistically significant (P less than 0.05). The prevalence of infection, the egg counts, and the seasonal incidence were related to the occupations and mode of transmission. The highest occupation prevalence of 60.92% occurred among the fishermen through water-borne transmission, while prevalence rates of 52.96% and 52.4% were recorded respectively through soil transmission. The difference between fishermen's prevalence and farmers' prevalence was statistically significant (P less than 0.01). Farmers' egg counts varied from 1,500 eggs per gram (epg) in the dry season to 7,500 epg in the rainy season. Fishermen's egg counts ranged from 3,000 epg in the rainy season to 8,000 epg in the dry season. The difference was not significant (P greater than 0.05). Among farmers the highest monthly incidence of 25% occurred in June, while the highest incidence of 35% occurred in fishermen in April. Incidence of infection among fishermen remained significantly higher (P less than 0.05) than in other occupation groups during the dry season months. Water-borne transmission of hookworm probably increases the incidence and egg counts among fishermen during the dry season.

Adolescent↗

Case reports: acute hookworm infection: an unusual cause of profuse watery diarrhoea in returned travellers.

We describe 3 returned travellers who developed profuse watery diarrhoea associated with marked blood eosinophilia. Delayed appearance of ova in stool samples caused difficulty in establishing diagnoses of acute hookworm infection. Low activity of ivermectin against hookworm resulted in failure of empiric treatment with this agent prior to parasitological diagnosis.

Acute Disease↗

Towards the eradication of hookworm in an isolated Australian community.

Hookworm (Ancylostoma duodenale) and other enteric parasites such as Giardia and Hymenolepis are common in Aboriginal communities in northem Australia, and their presence is associated with iron deficiency, anaemia, and failure to thrive. We report the outcome of a sustained, community-based control programme that used regular albendazole in one isolated community. Whereas hookworm has been effectively controlled by the programme, no sustained effect on the prevalence of Giardia and Hymenolepis was seen; the control of these parasites will depend on improvements in health education. This programme might serve as a model for community-based or population-based drug treatment programmes elsewhere.

Adolescent↗

The effect of the hookworm Ancylostoma ceylanicum on the mucosal architecture of the small intestine in hamsters.

Hookworms are known to cause marked changes to the intestinal mucosa, especially in relation to erosion of the villi. However, since the development of enteropathy has not been examined thoroughly through quantitative experiments on infected animals, the results of experiments conducted in hamsters infected with Ancylostoma ceylanicum are reported. Changes to intestinal architecture were first apparent between 12 and 14 days after infection, and then increased in intensity for 3-4 weeks, persisting for as long as worms were present (>63 days). Following infection, the height of villi declined from a mean of 1002 micro m in naïve controls to less than 200 micro m and as low as 18 micro m in one case. The depth of the crypts of Lieberkuhn increased from a baseline value of 166 micro m in naïve controls to in excess of 600 micro m within 6 weeks of infection. Mitotic figures had a baseline value of 5.5 per villus-crypt unit, and this rose to in excess of 25 in some experiments. Changes were dependent on the intensity of the parasite burden on day 20, but by 30 days after infection changes in all three values were maximal and density-dependent relationships were no longer clearly apparent. Villus height and crypt depth returned to near normal values within a week of the removal of worms, although group means for both remained different from naïve controls for at least 3 weeks after treatment. Cellular division, as reflected in numbers of mitotic figures, stayed elevated for over 5 weeks after removal of worms. The results suggest that enteropathy in hookworm infections stems from a combination of intestinal immune responses and from the grazing activities of the adult worms on the mucosal surface, but is not sufficient per se for expulsion of this parasite.

Ancylostoma↗

The public health importance of hookworm disease.

The public health significance of hookworm disease is briefly reviewed. The latest evidence confirms that blood loss caused by the worms' feeding activity in the gut is a contributing factor in the development of poor iron status leading to iron-deficiency anaemia. The World Health Organization has identified adolescent girls and women of child-bearing age as high-risk groups regarding the impact of hookworm disease. The merits of treating pregnant women with anthelminthic drugs after the first trimester are discussed.

Adolescent↗

Diagnosis of Oesophagostomum bifurcum and hookworm infection in humans: day-to-day and within-specimen variation of larval counts.

Oesophagostomum bifurcum, as well as hookworm infections are hyperendemic among humans in northern Togo and Ghana. For parasite-specific diagnosis a coproculture is obligatory, because only the infective larvae, and not the eggs, can be distinguished morphologically. The sensitivity of duplicate coprocultures from a single stool sample was found to be above 90% in comparison to a gold standard of 10 coprocultures made from a single stool specimen. Prevalence of infection with O. bifurcum and hookworm further increased with the number of coprocultures made from each individual stool. Notwithstanding the high sensitivity, intensity of infection per individual varied considerably from day-to-day and the number of larvae found in different samples out of 1 stool also varied highly, both showing a heterogeneous distribution. Surprisingly, daily fluctuation and within-specimen variation could not be differentiated from each other, probably because of the variation created by the coproculture technique. To estimate the intensity of infection, it is sufficient to make repeated coprocultures from only 1 individual stool sample. Laborious collection of stool samples on subsequent days does not give better estimates of the individual infection status.

Adolescent↗

Effectiveness of single doses of Fenbendazole Hoe 88I against Ascaris, hookworm and Trichuris in man.

Fenbendazole (Hoe 881) 5-(phenylthio)-2-benzimidazolecarbaminicacidmethylester in doses of 1-0 g and 1-5 g per person were effective against Ascaris and gave substantial egg count reductions against hookworm (mainly Necator americanus). The 1-5 g dose gave good results against Trichuris. In a trial with a suspension of Hoe 881 with a high specific surface of 25 m2/g there was no advantage over tablets with a specific surface of approximately 8 m2/g. Two doses of 500 mg given with an interval of 24 hours were no more effective than one dose of 1-0 g. In a comparative trial using Hoe 881 1-5 g, Pyrantel 10 mg/kg and placebo respectively Hoe 881 showed equal potency against hookworms and Acsaris as Pyrantel and good effectiveness against Trichuris. Pyrantel showed only moderate activity against Trichuris in this trial.

Adolescent↗

Selective primary health care: strategies for control of disease in the developing world. XVII. Hookworm infection and anemia.

Approximately one-quarter of the world's population is infected with either Ancylostoma duodenale or Necator americanus. Humans transmit the hookworm by fecal contamination of the soil. The eggs hatch and the larvae may survive several months in warm, damp soil. Humans are infected when the larvae penetrate the skin and migrate through the body to the intestines, where the median survival time of the hookworm is one year. The loss of red blood cells into the gut is proportional to the worm load. Symptoms result from iron deficiency anemia and protein loss caused by a heavy worm burden. The peak age-specific prevalence of infection occurs in adult life, but only a small proportion of those infected ever become symptomatic. Possible control measures include chemotherapy to reduce the intensity of infection and the transmission potential and sanitation.

Anemia, Hypochromic↗

Weight gain of Kenyan school children infected with hookworm, Trichuris trichiura and Ascaris lumbricoides is improved following once- or twice-yearly treatment with albendazole.

We studied growth in infected children given one dose (600 mg) or two doses of albendazole per school year. Children were examined and allocated at random within sex by descending hookworm egg count to one of three groups: placebo (n = 93), one dose (1x, n = 96) or two doses (2x, n = 95). Each child was treated and then re-examined and treated 3.6 and 8.2 mo later (Exams 2 and 3). The 1x and 2x groups gained significantly more by Exam 3 than the placebo group in weight (1.1 and 0.9 kg more, respectively), percent weight-for-age (3.3 and 2.7 percentage points more), percent weight-for-height (3.1 and 2.9 percentage points more), percent arm circumference-for-age (2.3 and 2.0 percentage points more) and triceps and subscapular skinfolds but did not differ significantly from each other. The placebo group showed significant decreases between exams (P < 0.0002) in percent weight-for-age and percent arm circumference-for-age and no change in percent weight-for-height, whereas the 1x and 2x groups exhibited significant increases (P < 0.005). At Exam 3, arithmetic mean egg reduction rates for the 1x and 2x groups were 84 and 95% for hookworm, 42 and 32% for Trichuris and 55 and 87% for Ascaris, respectively. We conclude that one or two doses of albendazole per year resulted in similar growth improvements, despite reinfection, in school-age children in an area where these helminths and poor growth are prevalent.

Albendazole↗

Physical fitness, growth and appetite of Kenyan school boys with hookworm, Trichuris trichiura and Ascaris lumbricoides infections are improved four months after a single dose of albendazole.

We studied physical fitness with the Harvard Step Test, growth, and appetite in primary school boys infected with hookworm (96% baseline prevalence), Trichuris trichiura (98% prevalence) and Ascaris lumbricoides (41% prevalence) who received a single 600-mg dose of albendazole or an identical placebo. Boys were examined, allocated at random within pairs by descending hookworm egg count to placebo (n = 26) or albendazole (n = 27) groups, treated, and re-examined 4 mo later. Four months after treatment, the albendazole group showed highly significant improvements in fitness score, resting heart rate, and heart rates at 1, 2, 3 and 4 min after the Harvard Step Test, whereas the placebo group had not changed significantly. The albendazole group also exhibited significantly more rapid growth judged by weight gain (1.0 kg greater than the placebo group, P < 0.0002), height increment (0.6 cm more, P < 0.003), arm circumference (0.3 cm more, P < 0.0002), and triceps and subscapular skinfolds (1.0 mm more, P < 0.0002), and showed improved appetite with objective and subjective measures. We conclude that single-dose treatment with albendazole can allow improved physical fitness, growth, and appetite in school-age children in areas where these helminths and poor growth are highly prevalent.

Adolescent↗

Malaria, hookworms and recent fever are related to anemia and iron status indicators in 0- to 5-y old Zanzibari children and these relationships change with age.

In Zanzibar and other tropical regions, iron deficiency, malaria and multiple helminth infections coexist. We addressed the following questions: 1) What are the predictors of low hemoglobin in Zanzibari preschool children? 2) Are indicators of iron status informative in this population? 3) Does malaria modify the relation of iron indicators to hemoglobin? We used multivariate regression to analyze cross-sectional data from a community-based sample of rural Zanzibari children who were not ill (n = 490; 4-71 mo of age) in whom we assessed hemoglobin, serum ferritin (SF), erythrocyte protoporphyrin (EP), serum transferrin receptor (TfR), recent fever, malaria parasitemia and helminth fecal egg counts. Of hemoglobin values, 80% were <100 g/L and 15.5% were <70 g/L. In children <18 mo of age, 40.2% of hemoglobin values were <70 g/L. Our primary findings were as follows: 1) In children <30 mo old, hemoglobin was associated with malaria but not hookworms, whereas in children >/=30 mo, hemoglobin was related to hookworms but not malaria. In the younger age group, male sex and recent fever also predicted lower hemoglobin. 2) The three iron indicators were informative in this population but did not reflect only iron status. Malaria elevated SF in younger children and TfR and EP in both age groups. Fever elevated SF in older children and EP in both age groups, but not TfR. 3) Malaria modified the relation of all three indicators to hemoglobin. The relation of SF to hemoglobin was weak overall, and absent in malaria-infected children. EP and TfR were strongly related to hemoglobin, but this relation was attenuated by malaria.

Age Factors↗

Endoscopic diagnosis of hookworm disease of the duodenum.

Hookworm is one of the most common parasites in the world, but can be missed on stool examination. We report a 31-year-old man who was complaining of epigastric discomfort, with laboratory findings of iron-deficiency anemia and eosinophilia. He was found to be infected with hookworm (Ancylostoma duodenale), which was directly detected and retrieved from the duodenum with biopsy forceps during upper gastrointestinal endoscopy. We eliminated his infection successfully by the Damaso de Rivas-Kihara modified method and oral administration of pyrantel pamoate. This report indicates that it is important to check carefully even in the distal duodenum at routine upper gastrointestinal endoscopy whenever parasitic disease is suspected but is hard to diagnose because of a limited number of eggs in feces.

Adult↗

Investigating hookworm genomes by comparative analysis of two Ancylostoma species.

BACKGROUND: Hookworms, infecting over one billion people, are the mostly closely related major human parasites to the model nematode Caenorhabditis elegans. Applying genomics techniques to these species, we analyzed 3,840 and 3,149 genes from Ancylostoma caninum and A. ceylanicum. RESULTS: Transcripts originated from libraries representing infective L3 larva, stimulated L3, arrested L3, and adults. Most genes are represented in single stages including abundant transcripts like hsp-20 in infective L3 and vit-3 in adults. Over 80% of the genes have homologs in C. elegans, and nearly 30% of these were with observable RNA interference phenotypes. Homologies were identified to nematode-specific and clade V specific gene families. To study the evolution of hookworm genes, 574 A. caninum/A. ceylanicum orthologs were identified, all of which were found to be under purifying selection with distribution ratios of nonsynonymous to synonymous amino acid substitutions similar to that reported for C. elegans/C. briggsae orthologs. The phylogenetic distance between A. caninum and A. ceylanicum is almost identical to that for C. elegans/C. briggsae. CONCLUSION: The genes discovered should substantially accelerate research toward better understanding of the parasites' basic biology as well as new therapies including vaccines and novel anthelmintics.

Ancylostoma↗