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Necator americanus (Nematoda: Ancylostomatidae) from Africa and Malaysia have different ITS-2 rDNA sequences.

The nucleotide sequences of the second internal transcribed spacer of rDNA were determined for adult worms of Necator americanus originating from Togo (Africa) and Sarawak (Malaysia). The length of the sequences of specimens from Togo (325 bp) were shorter than those from Sarawak (327 bp). There were six fixed genetic differences in the aligned sequences of N. americanus from Sarawak and Togo, excluding one or two polymorphic sites within the sequence of N. americanus from each geographical region. These findings suggest that there is either population variation in the sequence of N. americanus, or that N. americanus from the two countries may represent genetically distinct but morphologically similar (i.e. cryptic) species, however, comparison of the sequence differences among other hookworm species supports the latter conclusion.

Africa↗

Assessment of the effectiveness of primary health care interventions in the control of three intestinal nematode infections in rural communities.

In a 30 months' longitudinal study, primary health care intervention was effective in reducing the prevalence of three common intestinal nematode infections (Ascaris lumbricoides, Trichuris trichiura and Necator americanus) in three communities. This was achieved by training school leavers and auxiliary aides as microscopists, health inspectors and field assistants and deploying them to provide screening, surveillance, environmental sanitation, and mass-expulsion chemotherapy (MEC). Post-control surveillance confirmed that the prevalence of these infections had been greatly reduced. The prevalence of Ascaris lumbricoides had declined from 49.3% (pre-intervention) to 10.5% (post-intervention). Hookworm had fallen from 31.4% (pre-intervention) to 4.1% (post-intervention) and whipworm from 40.7% (pre-intervention) to 6.5% (post-intervention). Overall percentage decreases of 78.7%, 86.9% and 84.0% were recorded for Ascaris lumbricoides, Necator americanus and Trichuris trichiura respectively. The initial decline in prevalence was due to the MEC campaign, but the improved sanitation and health education presumably reduced the reinfection rate. If the entire population participated, periodic repetition of the mass expulsion therapy campaign at appropriate intervals combined with continued attention to environmental hygiene and prolonged health education could bring these infections under control within a few years.

Animals↗

Predisposition to hookworm infection in Papua New Guinea.

Reinfection with hookworm (Necator americanus) following chemotherapy was studied over 8 years in a rural village in Madang Province, Papua New Guinea. Faecal egg counts were performed on up to 202 individuals in July 1988, August 1990 and November 1996; the study population was treated after sampling in 1988 and 1990. Reinfection burdens in 1996 did not differ significantly from pretreatment burdens (in 1988), and were significantly higher than burdens in 1990. However, the prevalence of hookworm infection was significantly lower in 1996 than in either 1988 or 1990. There was significant predisposition to high or low hookworm burden between 1990 and 1996; this predisposition was stronger in children than adults. However, there was no detectable predisposition between 1988 and 1996 in individuals who had been treated 2 or more times between surveys. The mean weight of adult hookworms in individual hosts was measured in 1988 and 1990 using worms expelled after chemotherapy. There was a significant positive correlation between mean male hookworm weight in the 2 years, suggesting that individual hosts are predisposed to infection with heavy or light hookworms. These data suggest that differences in host susceptibility are involved in generating predisposition, but that longer-term variation in either exposure or susceptibility limits the period over which significant predisposition can be detected.

Adolescent↗

Albendazole therapy and reduced decline in haemoglobin concentration during pregnancy (Sierra Leone).

WHO recommends that anthelmintic treatment be included in strategies to improve maternal nutrition in areas where hookworms are endemic and anaemia is prevalent. At present, few countries have adopted this recommendation, partly owing to the lack of data to support the adverse effects of hookworms on maternal health. A longitudinal study was conducted on 125 women in Sierra Leone (in 1995/96) to measure the impact of single-dose albendazole (400 mg) and daily iron-folate supplements (36 mg iron and 5 mg folate) on haemoglobin and serum ferritin concentration during pregnancy. Women who received both albendazole and iron-folate supplements experienced no significant change (P > 0.05) in the prevalence of anaemia and iron-deficiency anaemia between the first and third trimesters. These prevalence levels significantly increased (P < 0.05) in women who received either albendazole or iron-folate supplements or neither. After controlling for baseline haemoglobin concentration and season, the mean decline in haemoglobin concentration between the first and third trimester in women who received albendazole was 6.6 g/L less than in women who received the control (P = 0.0034). The corresponding value for iron-folate supplements was 13.7 g/L haemoglobin (P < 0.001). The effects of albendazole and iron-folate supplements were additive. These findings lend support to WHO's recommendation for anthelmintic treatment during pregnancy.

Adolescent↗

The use of human faeces for fertilizer is associated with increased intensity of hookworm infection in Vietnamese women.

To investigate different factors associated with hookworm infections we conducted 2 studies in a commune in northern Viet Nam. The first was part of a larger study on anaemia and covered 213 women (15-49 years of age) and their 92 children (6 months to 5 years of age) in one commune; 90% of the families reported using human faeces for fertilizer. Women who reported using fresh human faeces as fertilizer had significantly higher hookworm egg counts than women who either used treated human faeces or who did not use human faeces as fertilizer. The second study examined how human faeces were used for fertilizer in 30 selected families. Women participated in preparation and application of human faeces to crops in 81% of the families using human faeces for fertilizer. Two methods of preparing the faeces were described: 48% of the families mixed the faeces with ash before applying them to the field; 18% mixed the faeces with water; 33% used both methods.

Adolescent↗

Comparison of the efficacy of mebendazole, albendazole and pyrantel in treatment of human hookworm infections in the southern region of Mali, West Africa.

A randomized, placebo-controlled trial of the efficacy of pyrantel (single dose 12.5 mg/kg bodyweight), mebendazole (single 500 mg dose) and albendazole (single 400 mg dose) in the treatment of hookworm infections (Necator americanus) was carried out in January 1998 in the Southern Region of Mali, West Africa, during the period of Ramadan (Islamic fast). Statistical analysis of the pre-intervention faecal egg counts showed that there was a significant pre-treatment chance bias, despite randomization of subjects into treatment groups, arising from the main effect of sex (heavier infections among males) and a sex x treatment interaction (the sex bias was not evident in the pyrantel-treatment group). The participants were re-examined 10 days after treatment, and after controlling for the drift in faecal egg counts in the placebo-treated subset, age, sex, fasting and intensity of infection, albendazole was clearly the most effective drug showing consistently efficacies in the range 92.1 to 99.7%, depending on the method of evaluation and the particular subset of the treatment group. Neither mebendazole nor pyrantel was as effective, with efficacies ranging from 60.9 to 89.8% and 4.8 to 89.7%, respectively. Fasting made no difference to drug efficacy. On the basis of our results the single 400 mg dose of albendazole is the treatment of choice for hookworm infections in this region of Mali. We emphasize the need for standardization of the methods used for trial designs, for calculation of summary data relating to drug efficacies and the accompanying statistical tests.

Adolescent↗

Patterns of concurrent hookworm infection and schistosomiasis in schoolchildren in Tanzania.

A cross-sectional study of 6897 schoolchildren in 59 out of the 155 primary schools in Magu District on the shores of Lake Victoria, Tanzania, was undertaken in 1997 to determine the prevalence of single- and multiple-species helminth infection. Schistosoma haematobium, hookworm (primarily Necator americanus) and S. mansoni were the most common helminth species infecting schoolchildren in the district. The prevalences of Ascaris lumbricoides and Trichuris trichiura were negligible (< 1%). Anaemia and stunting were highly prevalent and widespread. Hookworm and S. mansoni occurred more frequently in multiple infections with other helminths than as single-species infections, but triple-species infection was rare. Analysis of the frequency distribution of infection amongst schools showed that prevalences of S. haematobium and hookworm tended to be normally distributed, with medians 75% and 45%, respectively, while the distribution of S. mansoni was markedly skewed such that only 17% schools had a prevalence greater than 20%. An inverse association between S. mansoni and S. haematobium was observed. Geographical information system (GIS) analysis indicated that S. mansoni infection was highly prevalent only along the shore of Lake Victoria, whilst S. haematobium was homogeneously prevalent everywhere except the lakeshore. This pattern appears to reflect the distribution of schistosome species-specific snail intermediate hosts. The results imply that joint treatment for hookworm infection and schistosomiasis would be beneficial throughout the district.

Age Distribution↗

Is Necator americanus approaching a mutualistic symbiotic relationship with humans?

The hookworm Necator americanus establishes infections of impressive longevity in the immunologically hostile environment of its human host. In the process, it promotes pronounced T-helper 2 (Th2) cell activity, which in turn seemingly affords the host at least a degree of protection. Given the relatively asymptomatic nature of infection, we argue here that Necator americanus might be approaching a mutualistic symbiotic relationship with humans. In our view, infection is controlled by the immune system while being supported by a subtle immune-evasion strategy that is tolerated and possibly beneficial to the host in certain immunological circumstances, such as in counterbalancing potentially damaging Th1 responses.

Amino Acid Sequence↗

Necator americanus in infant rabbits: complete development, humoral antibody, leukocyte response and serum protein changes following infection.

Necator americanus, originally isolated from man, developed completely in infant rabbits (RSG-1). This infection was serially passed in infant rabbits up to the 6th generation without using any immunosuppressant. Two day old infant rabbits demonstrated a high degree of susceptibility to N. americanus. Studies revealed the retention of worms in the intestine for more than 150 days during which egg production was high. In this experimental model the leukocyte, antibody and serum protein responses due to N. americanus infection were monitored. Results showed that eosinophil numbers rose significantly from day 28 to 170. A maximum was observed on day 80 (41%) in rabbits of the fourth generation. Antibodies to N. americanus were detectable in infected rabbits by counterimmunoelectrophoresis using third stage larval antigen (Rabbit strain). Generally, total globulins increased with decrease in albumin. Serum protein increase was associated with alpha-2, beta and gamma globulin components.

Animals↗

Density-dependent effects on establishment of Necator americanus and Ancylostoma ceylanicum.

The relationships between the number of infective larvae (L3s) to which animals were exposed and the establishment of A. ceylanicum and N. americanus in hamsters were examined. There was no evidence of density-dependent constraints on the establishment of A. ceylanicum in the range 10-1000 larvae, but an experiment in which the range was extended to 1500 L3s gave a significant negative correlation between the magnitude of the infecting dose and percentage establishment. Even so the percentage reduction was relatively small, approximating to 0.89% per 100 larvae administered, and in practice density-dependent constrains on establishment are unlikely to affect experiments with this species in which much lower doses (< 250 L3) are generally employed. The range of doses for N. americanus L3s was smaller (10-400). Of the four experiments reported, two gave a significant reduction of establishment with increasing dose and two did not. When the data was split into low doses (< 100 L3s) and high doses (> 100 L3s), falling establishment with increasing dose was only detected in the lower dose range. There was no difference in the establishment when doses of 100 L3s were compared with 250 or 400 L3s. On balance, it was concluded that density-dependent constraints on establishment of N. americanus in hamsters were not marked and would have little significant effect on experiments utilizing fewer than 200 L3s (approximately 7.6% reduction between 10 and 200 L3s). These results are discussed in relation to host regulation of hookworm burdens.

Ancylostoma↗

Epidemiology and immunology of Necator americanus infection in a community in Papua New Guinea: humoral responses to excretory-secretory and cuticular collagen antigens.

Baseline data from an immuno-epidemiological study of hookworm infection in a rural village in Madang Province, Papua New Guinea are reported. Necator americanus was found to be the commonest helminth infection, with a prevalence of near 100% and intensity of 40 worms per host in adults. Enterobius vermicularis, Ascaris lumbricoides and Trichuris trichiura were also present, at prevalences of 53, 10 and 3% respectively; Ancylostoma duodenale was absent. The frequency distribution of N. americanus was highly over-dispersed, and was well described by a negative binomial distribution with aggregation parameter, k, of 0.370. Intensity of infection was significantly related to host age, but did not differ between the sexes. Haemoglobin levels and haematocrit values were indicative of anaemia in the community, but were unrelated to hookworm infection. Levels of antibodies (IgG, IgA and IgM combined) against adult Necator cuticular collagen and excretory-secretory (ES) products were determined. Serum concentrations of the two types of antibody were significantly correlated with each other. Significant positive correlations were found between anti-ES antibody levels and hookworm egg production, and between anti-collagen antibody levels and host age. It is suggested that the level of anti-collagen antibodies may reflect cumulative exposure to infection, whereas levels of anti-ES antibodies may be more dependent on current worm burden. No evidence was found to suggest that either antibody response is important in regulating parasite population growth. Similarly, the presence of a positive correlation between eosinophil concentration and infection intensity in adults indicates that eosinophilia reflects, rather than determines, the host's worm burden.

Adolescent↗

Reinfection with hookworm after chemotherapy in Papua New Guinea.

Reinfection with hookworm (Necator americanus) following chemotherapy was studied over 2 years in a rural village in Madang Province, Papua New Guinea. The prevalence of hookworm infection had returned to pre-treatment levels after 2 years, and the geometric mean hookworm burden had returned to 58% of the pre-treatment value. The rate of acquisition of adult worms was independent of host age, and was estimated as a geometric mean of 2.9-3.3 worms/host/year (arithmetic mean 7.9-8.9 worms/host/year). There was significant predisposition to hookworm infection; the strength of this predisposition did not vary significantly between age or sex classes.

Age Factors↗

Necator americanus in inbred mice: a re-evaluation of primary infection kinetics.

The course of a primary Necator americanus infection was studied in the lungs and small intestines of syngeneic mice. Following percutaneous infection no difference in initial larval establishment in the lungs was found between male BALB/c, NIH or B10.G mice. However, significant differences in the subsequent kinetics of infection were demonstrated between the BALB/c and NIH strains. Lung worm burdens declined more slowly in NIH mice than in BALB/c strain. Surprisingly, however, a greater proportion of larvae remaining in the lungs of BALB/c mice, 9 days p.i., were trapped than in NIH mice. Nevertheless, establishment in the small intestines of the BALB/c strain was consistently greater than in NIH mice. Host immunosuppression resulted in increased larval retention in the lungs of both the BALB/c and NIH strains as well as in the small intestines of BALB/c mice. Treatment with hydrocortisone acetate did not increase intestinal worm burdens in NIH mice. The data presented suggest that, in this complex, dynamic model system, designation of 'susceptible' and 'resistant' strains is inappropriate. The factors underlying the observed strain differences in resistance to infection are discussed.

Animals↗

Observations on the feeding behaviour of parasitic third-stage hookworm larvae.

The feeding behaviour of parasitic 3rd-stage larvae (L3) of the hookworms Ancylostoma caninum, A. ceylanicum and Necator americanus was examined. Less than 11% of A. caninum L3 recovered from the small intestines of dogs infected orally were feeding at 4-48 h post-infection (p.i.), and none of the A. ceylanicum L3 recovered from the intestines of orally infected hamsters had resumed feeding. All L4 of both species recovered at 36 and 48 h p.i. had resumed feeding. On the other hand, approximately 16% of the A. ceylanicum L3 recovered from the skin of percutaneously infected hamsters at 18 h were feeding, and the percentage feeding increased to nearly 58% at 44 h p.i. Necator americanus L3 recovered from the skin of percutaneously infected neonatal hamsters resumed feeding at 6-12 h p.i. and reached 90-94% by 18 h. Feeding began to decline at 66 h, and reached 29% at 120 h p.i. This decrease was associated with the migration of larvae from the skin to the lungs. By 192 h p.i. over 95% of the larvae had reached the small intestine, and all had moulted to the L4. The results indicate that parasitic L3 resume feeding in the skin during percutaneous infections, and suggest that feeding by hookworm L3 correlates with the resumption of development.

Ancylostoma↗