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We evaluated the effects of the Zanzibar school-based deworming program on the iron status of primary school children. Parasitologic and nutritional assessments were carried out at baseline, 6 mo, and 12 mo in 4 nonprogram schools (n = 1002), 4 schools in which students received twice-yearly deworming (n = 952), and 4 schools in which students received thrice-yearly deworming (n = 970) with 500 mg generic mebendazole. Schools were randomly selected for evaluation and allocated to program groups. Relative to no treatment, thrice-yearly deworming caused significant decreases in protoporphyrin concentrations and both deworming regimens caused marginally significant increases in serum ferritin concentrations. The average annual changes in protoporphyrin concentrations were -5.9 and -23.5 micromol/mol heme in the control and thrice-yearly deworming groups, respectively (P < 0.001). The average changes in ferritin concentration were 2.8 and 4.5 microg/L, respectively (P = 0.07). Deworming had no effect on annual hemoglobin change or prevalence of anemia. However, the relative risk of severe anemia (hemoglobin < 70 g/L) was 0.77 (95% confidence limits: 0.39, 1.51) in the twice-yearly deworming group and 0.45 (0.19, 1.08) in the thrice-yearly deworming group. The effects on prevalence of high protoporphyrin values and incidence of moderate-to-severe anemia (hemoglobin < 90 g/L) were significantly greater in children with > 2000 hookworm eggs/g feces at baseline. We estimate that this deworming program prevented 1260 cases of moderate-to-severe anemia and 276 cases of severe anemia in a population of 30,000 schoolchildren in 1 y. Where hookworm is heavily endemic, deworming programs can improve iron status and prevent moderate and severe anemia, but deworming may be needed at least twice yearly.

To determine the inflammatory and immunological mechanisms associated with live third-stage (L3) hookworm larval vaccines, mice were immunized either subcutaneously or orally with three doses of 500 L3 of Ancylostoma caninum at 2-week intervals, and then challenged percutaneously (via abdominal skin) with 500 L3. Non-immunized mice served as negative controls. Skin was excised from post-challenge mice at intervals between 6 h and 28 days, and then examined by light microscopy. In non-immunized mice the L3 exhibited no structural damage and infiltrating inflammatory cells were absent from the surrounding tissues. There were no changes in the cutaneous architecture. In contrast, skin recovered from the immunized mice was edematous and exhibited marked inflammatory changes with resultant destruction of the challenge L3. At 6 h post-challenge the L3 exhibited cuticular swelling and damage; the surrounding tissue was infiltrated by polymorphonuclear inflammatory cells. By 24 h granulomata in the dermis, subcutaneous tissues and underlying abdominal muscles were first observed surrounding dead L3. The number of granulomata peaked at 72 h, with the majority distributed in the subcutaneous tissues. Plasma cells predominated in the early granulomata, but by 3-7 days post-challenge foreign body giant cells began to appear. In some cases, intact and presumably living L3 were noted in the abdominal muscles 14-28 days post-challenge, which suggested that protection against larval challenge was not absolute. Granuloma formation appears to be a major component of the post-vaccination murine host immune response against challenge larvae. The observation generates several hypotheses to investigate the mechanisms of protection afforded by living helminth vaccines.

Four experiments are described in which hamsters, initially exposed to primary infection with Ancylostoma ceylanicum, were given a homologous challenge and components of the secondary response were quantified and compared to relevant control groups. The initial establishment of the L3 larvae was not prevented in immunized hamsters but their growth was slowed and virtually all larvae were lost within a week of challenge, when the majority were still at the L4 stage of development. The loss of worms was associated with an accelerated mucosal mastocytosis and increased systemic antibody. Thus acquired immunity to hookworm larvae in this system acted on L3 and L4 stages, thereby preventing larvae from maturing in immunized animals. In contrast to primary infections, immunized hamsters responding to a challenge infection did not lose weight nor did they experience significant anaemia, because of the lack of adult worms. The secondary immune responses therefore prevented manifestation of hookworm disease among immunized-challenged animals.

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

The purpose of this study is to assess the impact of improvement measures for hygiene and water supply, installation of latrines and health education on the incidence of ascaridiasis and ankylostomiasis with 2 to 4 years old children in some villages of southern Côte d'Ivoire. The method used is the comparison of children carrying parasites before and after intervention. Initially in 1988, the stools of all children aged from 2 to 4 were collected and examined in order to look for the presence of parasites in the stools. Two identical inquiries were made in 1990 and 1992. The results show a reduction of the rate of incidence for ascaridiasis by 75% and ankylostomiasis by 82%. They demonstrate the importance of an appropriate evacuation of excreta, of an education of mothers and of domestic hygiene in the process of prevention of children parasitosis.

Ancylostoma-secreted protein 1 (ASP-1) is the major protein secreted by infective hookworm larvae (Ancylostoma caninum). The Escherichia coli-expressed recombinant protein was evaluated as a vaccine antigen in a mouse model of ancylostomiasis. A. caninum larvae migrate through mouse lungs, with maximal migration occurring 48-54 h after oral infection. Quantitative larval recovery from the lungs at this time was used as an end point for vaccine evaluation. All mice developed antibodies to recombinant ASP-1 (rASP-1) after immunization and boosting with the alum-precipitated protein. The immunized mice had their worm burden reduced 79% (P < .0001) compared with controls. Immunization with rASP-1 in the presence of Corynebacterium parvum adjuvant also showed a vaccine effect (63% protection; P < .0001). The possibility that this protective effect resulted from delayed larval lung entry was excluded. rASP-1 offers promise as a hookworm vaccine antigen.

Anthelminthic drug chemotherapy has failed as an acceptable approach to hookworm control in the less developed countries of the tropics. The development of a genetically engineered vaccine against hookworm infection would be a major advance in our efforts to control this parasitic disease. We have produced several lead recombinant hookworm vaccine antigens. Their development is based on scientific principles that were generated almost 70 years ago when investigators first began to attenuate living infective hookworm larvae. Those early studies on attenuated live vaccines highlighted the importance of secreted larval antigens for eliciting protective immunity in dogs challenged with Ancylostoma caninum. The two major secreted larval antigens have been recently identified as Ancylostoma secreted protein-1 (ASP-1) and ASP-2. The predicted amino acid sequences of the ASP cDNAs together with experimental immunogenicty data using the expressed recombinant protein suggest that the ASPs are promising vaccine antigens. Preliminary hookworm challenge data in mice immunized with recombinant ASP-1 helps to validate this assumption. Alternative vaccines based on either genetic immunization (DNA vaccines) or immunization with recombinant molecules expressed from adult hookworm cDNAs are also under evaluation. Optimization of vaccine route, delivery system, and adjuvant formulations will be required before future planned phase I testing in humans. Vaccine development for a target population living in rural areas of less developed countries will require innovative solutions to financing and manufacture.

Correlation between the degree of protection and induced serum antibody response in hamsters immunized with somatic and excretory-secretory (ES) antigens of adult. A. ceylanicum was investigated. Hamsters were immunized with non purified and Sephadex G-200 fractions (F1, F2 and F3) of somatic and ES antigens. The degree of protection was assessed in terms of percent worm reduction compared to controls against challenge infection. Induced humoral antibody response was determined by ELISA. Both somatic and ES antigens had shown moderate to significant protection but the latter was found more immunogenic as highest level of protection (67.02%) was achieved by these antigens. Humoral antibody was found highly elevated in animals immunized with protective doses of somatic and ES antigens. The maximum serum antibody titer i.e. 1:3200 was noticed in animals immunized with high protective dose (64.59% protection) of fraction F1 of ES antigens. Antibody titer correspond to the degree of protection and a positive correlation between induced humoral antibodies and protection level was established.

It retards growth and intellectual development in millions of children yet is largely ignored by researchers. New findings suggest excellent possibilities for a vaccine.

Forty 11- to 12-week-old helminth-naive Beagles were categorized by sex and weight and randomly assigned to 4 treatment groups (group 1, ivermectin/pyrantel pamoate; group 2, milbemycin oxime; group 3, untreated control; group 4, diethylcarbamazine/oxibendazole). Each pup was inoculated PO with approximately 100 infective Ancylostoma caninum larvae and 100 larvated Toxocara canis eggs on day 0, and repeatedly at 7-day intervals thereafter until day 56. Administration of anthelmintics also began on day 0, and subsequent treatments were administered according to label recommendations at 30-day intervals (groups 1 and 2) or daily (group 4) for a period of 90 consecutive days. Body weight and A caninum and T canis fecal egg counts were measured at weekly intervals, and clinical observations of health status were conducted twice daily. Pups were euthanatized on day 90, and total gastrointestinal worm burdens were determined. Compared with mean A caninum egg counts of group-3 control pups, egg counts in group-1 pups were significantly (P < or = 0.0001) lower on every sampling days 35, 42, 49, 63, 70, 77, and 84, and were consistently the highest of all treated groups, and egg counts of group-4 pups were significantly (P < or = 0.0001) lower on every sampling date from day 14 to day 90, and were consistently the lowest of all treated groups. Compared with mean A caninum egg counts of group-3 pups, egg counts in group-1 and group-2 pups were lower by 97.8 and 90.8%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To document the distribution of human hookworm infection in Australia., Design: A retrospective study of published data and accessible archival records., Methods: The core data were derived from the report of the Australian Hookworm Campaign, annual reports of various State health departments and the Queensland Institute of Medical Research, and unpublished files of the former Queensland Aboriginal Health Programme., Findings: Today, hookworm infection is endemic only among Aboriginal communities of northern Western Australia and the Northern Territory, where Ancylostoma duodenale may be the sole species. Early this century, infection was also established in Queensland and northern New South Wales, in both Aboriginal and white communities, and Necator americanus predominated. The origin of these parasites is obscure. Sustained control programs seem to have eradicated hookworms from Queensland., Conclusions: Improved sanitation, hygiene and chemotherapy have eliminated hookworms from white populations of Australia. Continued anthelminthic campaigns will also clear the parasites from Aboriginal communities, but unless living conditions improve significantly infection will recur.

Methyl [5-[[4-(2-pyridinyl-1-piperazinyl] carbonyl]-1H- benzimidazol-2-yl] carbamate (CDRI Compound 81-470) exhibits a long prophylactic action against experimental ancylostomiasis, when given parenterally but not orally. To find out an explanation for such a behaviour, metabolic disposition studies were performed in hamsters using [3H] compound 81-470. Following intramuscular administration, the compound was found to form a depot at the site of injection and to remain there in substantial amount for more than 7 weeks. The compound was fairly distributed in all the organs studied and the presence of radioactivity could be easily detected up to 7 weeks of observation period. The compound was very slowly eliminated from the body and only 38% of the radioactivity could be recovered in the urine and faeces during 14 days. The oral dose, to the contrary, was poorly absorbed and more than 62.8% was excreted in the faeces within 48 hr. Consequently, this dose yielded lesser area under plasma curve. More than 95% of the oral dose was eliminated within a week and hardly and radioactivity could be detected in the tissues after day 14. In accord with this pattern, in blood also the im dose was detected up to 7 weeks while the orally given compound reached undetectable level within 6 days only. The lower clearance and prolonged stay in the body of the im dose compared to quick elimination of the oral dose may be responsible for the long chemoprophylactic action of compound 81-470 when given through im route.

To delineate mechanisms involved in the prophylactic action of methyl [5-[[4-(2-pyridinyl)-1-piperazinyl]-carbonyl]-1H-benzimidazol-2 yl] carbamate (compound 81/470) in hamster against Ancylostoma ceylanicum infection, plasma level of the compound and status of reactive oxygen metabolites in jejunum at different periods of the drug treatment were examined. The compound was found to enhance the generation of both O2- and H2O2 by the jejunum possibly by activating xanthine oxidase. This stimulation was found to be both time and dose dependent. At 100 mg/kg dose the increase in O2- production could be recorded at least upto 50 days, whereas at 25 mg/kg the stimulation remained effective upto 20 days only, and at 5 mg/kg there was no change in the activity. This correlated well with the reported prophylactic pattern of the compound i.e. upto 45 and 7 days by 100 and 25 mg/kg doses, respectively. Plasma level of the compound also exhibited dose dependent variation. The compound given at 100 mg/kg dose could be detected in significant concentration upto at least 42 days while that given in 25 and 5 mg/kg doses was present in equivalent concentration upto 14 days and 1 day, respectively. It is concluded that the activation of respiratory burst in the jejunum induced by the persistent presence of compound 81/470 may represent one of the important mechanisms for the chemoprophylactic activity of this anthelmintic.

Fujian province has been known to be endemic for mixed hookworm infection with Ancylostoma duodenale as the predominant species. The infection rate was 50% before 1980. As a result of mass treatment starting from 1980, the infection rate was decreased in most areas. And, infection foci were changed from sweet potato fields to the banana, sweatcane and asparagus fields where the infection rate tended to increase. It is stressed that the current endemic characteristics of hookworm infection should be paid more attention in implementing the control programme of hookworm infection.

Three different control schemes including selective chemotherapy, a combination of selective chemotherapy and management of fecal disposal and mass treatment with mebendazole-medicated salt were implemented for the control of hookworm infection in Luwo Town and Taiping Village, Wuming County, Guangxi Zhuang Autonomous Region during 1971-1990. Through ten years of selective chemotherapy, the results showed that the hookworm infection rate dropped from 42.6% to 3.9% and the infection intensity from 425.6 eggs per gram faeces to 1.6 eggs per gram faeces. After seven years of selective chemotherapy combined with management of fecal, the hookworm infection rate dropped from 58.7% to 10.9% and the infection intensity from 111.5 eggs per gram faeces to 8.5 eggs per gram faeces. However, 3 years after the termination of the combined treatment, the hookworm infection rate increased to 14.5%. As for the implementation of the third scheme, mebendazole-medicated salt was given at 100 mg daily for 30 consecutive days or at 50 mg daily for 30 consecutive days. Stool examination was made one year after the treatment, the results showed that the infection rate of the inhabitants dropped from 36% and 36% to 2% and 1.3%, respectively, and the infection intensity dropped from 110.3 and 246 eggs per gram faeces to 1.3 and 0.24 eggs per gram faeces. After three years, the infection rate of inhabitants remained under 2% and the infection intensity under 1 egg per gram faeces. It was concluded that mass treatment with mebendazole-medicated salt might be the most practical scheme for the control of hookworm infection.

Infections with Ancylostoma caninum are transmitted orally or percutaneously. The transmission of infectious stages with the milk of particular importance for the distribution of the species. It occurs during the dissemination of larvae that follows every infection as well as after reactivation of resting somatic larvae in the bitch at the end of the pregnancy. The galactogenic transmission of larvae occurs even when, due to existing immunity, no patent infections develop in the bitch. Immunity does not or only to a low extent influence impatient infections or the migration of reactivated somatic larvae. It also allows a limited reestablishment of a deposit of larvae in the bitch. Following percutaneous infection dermatitis occurs in the area of larval penetration and the lung is affected by migrating larvae. Intestinal stages of Ancylostoma caninum damage the host by ingestion of the mucosa of the small intestine and withdrawal of blood. Main symptoms of ancylostomiasis are a mucous haemorrhagic diarrhoea and anaemia, that become visible 8 to 10 days post infection. The examination for impatient infections with Ancylostoma caninum can be done by immunofluorescence and ELISA. With both methods antibodies against third stage larvae can be detected from the first or second week post infection onward. Patent infections with Ancylostoma caninum can easily be detected by faecal examination for the presence of the characteristic oval, thin-walled eggs containing few blastomeres. Galactogenic infections with Ancylostoma caninum can be prevented or reduced by a regular treatment of the bitch with albendazole, fenbendazole or oxfendazole during the activation of larvae in the last third of the pregnancy or by repeated treatment with ivermectin shortly before and after birth. To prevent patent infections, galactogenic infected puppies have to be treated early and repeatedly.

A systematic, random sample of 450 small and mixed-animal practitioners was selected from the client list of a prominent veterinary pharmaceutical and animal health company. A telephone survey was conducted, using a standard questionnaire, to assess whether current veterinary practices concerning prophylaxis and treatment of canine roundworm (Toxocara canis) and hookworm (Ancylostoma spp) infections are adequate to prevent transmission to human beings. Analysis of results focused on 3 questions related to prevention: practitioner's frequency of client education regarding zoonotic potential of roundworms and hookworms, pup age at which veterinarian recommends first anthelmintic treatments, and proportion of veterinarians recommending prophylactic drug administration for pups and nursing bitches. Despite the proven association of household pet dogs and human toxocariasis, only a third (148/450) of veterinarian respondents routinely discussed the potential zoonotic hazards of canine roundworms with their clients. A total of 29% (130/450) of veterinarians surveyed either never discussed these potential hazards or discussed them only when asked by their clients. With regard to anthelmintic treatment practices, 31% (140/450) of veterinarians surveyed recommended that pups first be examined and treated for intestinal parasites within 4 weeks of age. Thirty-three percent (163/450) recommended first examination and deworming at 5 to 6 weeks of age, and 36% (163/450) suggested that it be done at or after 7 weeks of age. Less than half (208/450) of veterinarians administered anthelmintics prophylactically to at least some pups and dogs. Sixty-four percent (287/450) of respondents recommended routine testing and treatment of nursing bitches.(ABSTRACT TRUNCATED AT 250 WORDS)

When dogs were immunized with soluble extract of adult Ancylostoma ceylanicum antigen, they were partially resistant to challenge infection in this model of human hookworm infection. Two immunizing doses, each of 1 mg protein suspended in Freund's complete adjuvant, were administered to one group of animals 1 and 3 weeks prior to infection with 5000 larvae. When compared with control dogs given the same infective dose, fecal egg excretion and intestinal adult worm burden in the immunized animals were reduced by 59 and 74%, respectively. Infection had no significant effect on hemoglobin concentrations, mean red cell volumes, total white cell counts, platelet levels, or spontaneous and phytohemagglutinin-induced lymphocyte transformations in both control and immunized animals. Both groups developed an eosinophilia, and lymphocytes from the immunized dogs responded transiently to stimulation with both larval and adult worm antigens. Specific IgM antibodies were transitory in both groups of dogs following infection. IgG antibodies developed significantly 2 weeks after infection in the immunized group; however, they did not appear until 4 weeks after infection in the control group. Both groups developed IgA antibodies 1 week after infection. They were maintained in the control dogs, in contrast to the levels in immunized animals which subsided rapidly 4 weeks after infection. Therefore, when animals are injected with soluble adult worm antigen prior to infection, specific protective immunity is acquired.

Three types of vaccine (1) a sonicated extract of killed larvae, (2) 5-fluorouracil-treated larvae and (3) 40 krad. X-irradiated larvae have been evaluated. Pups aged 3-4 months, weighing 2 +/- 0.5 kg and free of natural hookworm infection were selected for experimental studies. The sonicated extract was given either in a single dose or as 2 doses at weekly intervals, whereas the 5-fluorouracil-treated and X-irradiated larvae were given in a single dose only. After completion of the vaccination schedule, the pups were challenged with filariform larvae and were sacrificed 3 weeks after challenge. Non-vaccinated pups and those vaccinated with a single dose of sonicated extract lost weight and had diarrhoea or dysentery after challenge. Furthermore, in non-vaccinated pups, haemoglobin levels fell and at autopsy the intestinal mucosa was found to be grossly congested and free blood was present in the lumen of the intestine. Such findings were not obtained in pups vaccinated with the other types of vaccines. The percentage of infective larvae which developed to the adult stage in non-vaccinated pups was 82.7 +/- 9.53 compared with 45.1 +/- 12.33, 30.1 +/- 10.05, 20.6 +/- 10.60 and 8.0 +/- 7.46%, respectively in pups vaccinated with a single dose of sonicated extract, double dose of sonicated extract, 5-fluorouracil-treated and 40 krad. X-irradiated larval vaccines. While the irradiated larval vaccine provided maximum protection against clinical ancylostomiasis, 2 doses of the sonicated larval vaccine could also afford almost equal protection to pups.

A vaccination trial in golden hamsters with UV-irradiated infective larvae of Ancylostoma ceylanicum was attempted. One oral vaccination of hamsters with 100 infective larvae irradiated by means of UV-tube (390 nm) at different time intervals induced the development of resistance. As the time exposure of irradiation was increased, there was a corresponding decrease in the subsequent worm establishment. A high level of protection afforded by larvae irradiated for 15 min UV-exposure was recorded giving 99.0% and 95.0% worm reduction against the challenge doses of 100 and 1000 normal larvae respectively. There was no marked difference in worm establishment in hamsters vaccinated either orally or subcutaneously, followed by oral challenge. In the vaccinated hamsters, the manifestations of resistance at 15 min UV-exposure were shown by marked reduction in worm establishment and highly reduced epg in pellets with significantly higher blood haemoglobin levels compared with those given normal larvae as vaccine and challenge controls.

Ninety-, 60-, and 40-percent population coverages with levamisole 2.5 mg/kg of body weight were compared for their effects on Ascaris lumbricoides, ancylostoma, Strongyloides stercoralis, and Trichuris trichiura infections. They were shown to be effective in maintaining a reduced prevalence of A. lumbricoides in the treated subjects for 9, 6, and 3 months, respectively. Nine months after treatment, the prevalence of ascariasis was still lower than before treatment both in the levamisole and in the control subjects, regardless of the population coverage. This was probably because the egg output had been reduced. It is concluded that mass treatment with single oral doses of levamisole repeated at 3-month intervals might help control ascariasis, and that population coverages between 60 and 90% might be appropriate. No clear-cut effects against hookworms could be shown, possibly because the first follow-up examinations were performed three months after treatment. No changes in the prevalence of S. stercoralis and T. trichiura could be demonstrated. There were no adverse exp

The prophylactic action of a substituted methylbenzimidazole carbamate was investigated against experimental nematode infections. The compound at the dose of 100 mg/kg x 1, i.m., protected hamsters against Ancylostoma ceylanicum for about 45 days and at 500 mg/kg x 1 protected rats against Nippostrongylus brasiliensis for 28 days. The uteri of female worms recovered from treated animals were devoid of ova so long the compound had considerable phophylactic action. In case of A. ceylanicum the compound exerted lethal action on L4 stage and in N. brasiliensis, mild action was noticed on L4 which became more pronounced on L5. The reference drugs, mebendazole and thiabendazole, had weaker prophylactic action.

Coprological examinations were made in 358 foreigners, 51 of which (14.2%) were positive from the point of view of hookworm eggs presence. On the basis of the discovered infection prevalence, which is still high in foreigners arriving to the CSSR from the tropics and subtropics and on the basis of the new information about the developmental cycle of Ancylostoma duodenale the author recommends to alter the so far valid antiepidemic measures in the following sense: Persons should be regarded as parasitologically negative to hookworm infection, if their coprological examination is permanently negative within 40 weeks of their stay in the CSSR.