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At least 19 recordsLinked to original sources
PubMed2003

Progress in the development of a recombinant vaccine for human hookworm disease: the Human Hookworm Vaccine Initiative.

Hookworm infection is one of the most important parasitic infections of humans, possibly outranked only by malaria as a cause of misery and suffering. An estimated 1.2 billion people are infected with hookworm in areas of rural poverty in the tropics and subtropics. Epidemiological data collected in China, Southeast Asia and Brazil indicate that, unlike other soil-transmitted helminth infections, the highest hookworm burdens typically occur in adult populations, including the elderly. Emerging data on the host cellular immune responses of chronically infected populations suggest that hookworms induce a state of host anergy and immune hyporesponsiveness. These features account for the high rates of hookworm reinfection following treatment with anthelminthic drugs and therefore, the failure of anthelminthics to control hookworm. Despite the inability of the human host to develop naturally acquired immune responses to hookworm, there is evidence for the feasibility of developing a vaccine based on the successes of immunising laboratory animals with either attenuated larval vaccines or antigens extracted from the alimentary canal of adult blood-feeding stages. The major antigens associated with each of these larval and adult hookworm vaccines have been cloned and expressed in prokaryotic and eukaryotic systems. However, only eukaryotic expression systems (e.g., yeast, baculovirus, and insect cells) produce recombinant proteins that immunologically resemble the corresponding native antigens. A challenge for vaccinologists is to formulate selected eukaryotic antigens with appropriate adjuvants in order to elicit high antibody titres. In some cases, antigen-specific IgE responses are required to mediate protection. Another challenge will be to produce anti-hookworm vaccine antigens at high yield low cost suitable for immunising large impoverished populations living in the developing nations of the tropics.

Adolescent↗
PubMed2005

Antibodies against a secreted protein from hookworm larvae reduce the intensity of hookworm infection in humans and vaccinated laboratory animals.

The development of a vaccine would provide an important new tool for the control of human hookworm infection. On the basis of successful vaccination of laboratory animals with living irradiated, third-stage hookworm larvae (L3), we examined the antibody responses of individuals from hookworm endemic areas of Brazil and China against the most abundant L3 secreted antigens, the ancylostoma secreted proteins, ASP-1 and ASP-2. Logistic regression was used to investigate the effects of antibody isotype responses to ASPs on the risk of an individual harboring heavy hookworm infection. A significant protective association was observed between increasing anti-ASP-2 IgE levels and the risk of heavy hookworm infection. To confirm that ASP-2 is a protective antigen, laboratory dogs were immunized with recombinant ASP-2 formulated with the GlaxoSmithKline Adjuvant, AS03. Sera obtained from the immunized dogs exhibited high geometric mean antibody titers, immunoprecipitated native ASP-2 from L3 extracts and localized the site of ASP-2 expression to the glandular esophagus and body channels exiting to the cuticle. The sera also exhibited an increased ability to inhibit migration of L3 through tissue in vitro relative to sera from AS03-injected controls. Upon L3 challenge, the ASP-2 vaccinated dogs exhibited significant reductions in fecal egg counts and intestinal hookworm burden. These findings provide strong support for the development of an effective recombinant vaccine against hookworm infection in humans.

Adolescent↗
PubMed2006

Age-related changes in hookworm infection, anaemia and iron deficiency in an area of high Necator americanus hookworm transmission in south-eastern Brazil.

Surprisingly few detailed age-stratified data exist on the epidemiology of hookworm and iron status, especially in Latin America. We present data from a cross-sectional survey examining 1332 individuals aged 0-86 years from a community in south-east Brazil for hookworm, anaemia and iron deficiency. Sixty-eight percent of individuals were infected with the human hookworm Necator americanus. The force of infection (lambda=0.354) was similar to estimates from other areas of high hookworm transmission. Individuals from poorer households had significantly higher prevalence and intensity of infection than individuals from better-off households. The prevalence of anaemia, iron deficiency and iron-deficiency anaemia was 11.8%, 12.7% and 4.3%, respectively. Anaemia was most prevalent among young children and the elderly. Univariate analysis showed that haemoglobin and serum ferritin were both significantly negatively associated with hookworm intensity among both school-aged children and adults. Multivariate analysis showed that, after controlling for socio-economic status, iron indicators were significantly associated with heavy hookworm infection. Our results indicate that, even in areas where there is a low overall prevalence of anaemia, hookworm can still have an important impact on host iron status, especially in school-aged children and the elderly.

Adolescent↗
PubMed2005

The impact of concurrent and treated Ancylostoma ceylanicum hookworm infections on the immunogenicity of a recombinant hookworm vaccine in hamsters.

BACKGROUND: The effect of concurrent (active) and treated hookworm infections on the immunogenicity of vaccination with the recombinant fusion protein Ay-Ancylostoma-secreted protein 2 was analyzed in the Golden Syrian hamster. METHODS: Hamsters were infected with the hookworm Ancylostoma ceylanicum and vaccinated with the recombinant protein, with Quil A used as adjuvant. As controls, hookworm-infected hamsters were treated with the anthelmintic drug pyrantel pamoate before vaccination. Naive hamsters (i.e., those with neither previous hookworm infections nor treatment) were also vaccinated. RESULTS: The proliferation capacities of carboxyfluorescein diacetate succinimidyl ester-positive lymphocytes from the hookworm-infected vaccinated group were reduced by 50% relative to the capacities of lymphocytes from uninfected or treated vaccinated hamsters; capacities were comparable to the rates observed in lymphocytes from the hamsters vaccinated with the adjuvant alone. Immunoglobulin G1 antibody responses were also reduced in the actively infected, untreated hamsters, and interferon- gamma and interleukin-4 cytokine mRNAs were down-regulated. Conversely, interleukin-10 and tumor necrosis factor- alpha mRNAs were up-regulated in those hamsters. CONCLUSIONS: These results suggest that hookworm infections have an immunomodulatory effect by impairing the immune response to an exogenous antigen during infection. The hookworm-associated immunodepression may have important implications for design of clinical trials of human vaccines and vaccination strategies.

Adjuvants, Immunologic↗
PubMed1994

Detection of hookworm and hookworm-like larvae in human fecocultures in Suriname.

Estimation of the prevalence of hookworm infection is usually based on finding eggs of the parasite in the stool. Eggs of the different hookworm species are difficult to distinguish and can be confused with those of hookworm-like species. Proper identification can be made after hatching the eggs and cultivating larvae to the infective stage. We have used the Harada-Mori method to study the stools of Bushnegroes in Suriname and have identified the emerged larvae. Of the 804 individuals examined, 53.6% had positive fecal cultures. The identification of emerged larvae revealed that 75% of the positive cultures contained Necator americanus and Strongyloides stercoralis was detected in 19.7%. Oesophagostomum and Ternidens species were also found. Ancylostoma duodenale larvae were not found. Six percent of fecal cultures in which larvae emerged contained only hookworm-like larvae hatching from eggs that resembled hookworm eggs. The diagnosis of hookworm infection, based solely on the microscopic detection of eggs in the stool, must be considered with special caution.

Ancylostomatoidea↗
PubMed1978

Population biology of hookworms in children in rural West Bengal. II. Acquisition and loss of hookworms.

From changes in hookworm egg counts in feces of children in Gangetic West Bengal we estimate that, on the average, each child lost about 11.1 female hookworms during the 1969 post-monsoon dry period and gained about 10.3 females during the subsequent premonsoon and monsoon seasons, resulting in a net loss of worms over the 22-month study period. However, the mean fecal egg count for each 1-year age group of children from 3-11 years suggests an average net gain of 2.7 female worms/year. From seasonal changes in the relative abundance of larvae recovered from fecal cultures, it is estimated that at least 82% of the yearly gain in Ancylostoma duodenale females is a result of the maturation of hypobiotic (latent) larvae acquired during the previous wet season. A duodenale was present about equally with Necator americanus but it was significantly more common among males than among females, and more common among Muslims than among Hindus. Using damp gauze pads, we sampled the soil surface around freshly-passed feces for infective hookworm larvae and estimated that 252 larvae were contacted by each child durint the transmission season. Efficiency of penetration and maturation of each hookworm species was calculated from estimated larval densities on the soil surface, from seasonal changes in fecal egg counts, and from variations in the number of larvae recovered from fecal cultures by season and age of the host; it is estimated that N. americanus is 17.5% efficient and A. duodenale 5.3%. Children negative for hookworm became positive at all times of the year and at a significantly higher rate in 1970 than in 1969; incidence averaged 4.2% per 2-month period and mean initial fecal egg count suggested infection with about 2.0 female worms. The average life span for N. americanus is calculated to be 3-4 years and that of A. duodenale about 1 year under the conditions of reinfection found in the study area.

Ancylostoma↗
PubMed1980

Pathogenicity of hookworms. The significance of population regression for the pathogenicity of hookworms.

A method is described to estimate the reduction of the hookworm population in the host during the infection period (population regression). A formula is proposed to estimate the average worm population during the infection period, on the assumption that a decreasing hookworm population causes a decrease in daily blood loss. Daily blood loss per worm was calculated for Ancylostoma caninum: 43 microliters; for A. ceylanicum: 14 microliters for A. braziliense: 5 microliters. Accordingly hookworms cause blood loss one half to two thirds smaller than formerly assumed.

Ancylostoma↗
PubMed1977

Skin penetration of infective hookworm larvae. III. Comparative studies on the path of migration of the hookworms Ancylostoma braziliense, Ancylostoma ceylanicum, and Ancylostoma caninum.

The lateral skin areas of nine hookworm-free puppies were exposed to infective larvae of Ancylostoma braziliense, Ancylostoma ceylanicum and Ancylostoma caninum. Serial sections, stained with Harris' haematoxylin and eosin, showed that many similarities exist in the migration patterns of the hookworm species used. However, striking differences were observed between Ancylostoma braziliense on the one hand and Ancylostoma ceylanicum and Ancylostoma caninum on the other hand with regard to the speed with which the penetration occurred. Larvae of Ancylostoma braziliense may travel directly from the epidermis into the dermis--apart from migration via hair follicle systems--a path of migration we did not observe in infections with the other species used. Larvae of Ancylostoma braziliense seem to pass the skin more rapidly than those of Ancylostoma ceylanicum and Ancylostoma caninum. Many larvae of Ancylostoma ceylanicum managed to penetrate the skin 2--6 h after the onset of the exposure.

Ancylostoma↗
PubMed2004

Comparison of mitochondrial cytochrome oxidase 1 DNA sequences from Necator americanus hookworms maintained for 100 generations in golden hamsters (Mesocricetus auratus) and hookworms from natural human infections.

The human hookworm Necator americanus was maintained through one hundred generations in the golden hamsters. The strain is now routinely maintained in laboratory hamsters through serial passage, and is the laboratory strain of choice for vaccine studies. Comparison of the mitochondrial cytochrome oxidase 1 (cox-1) sequences was shown previously to be useful for comparing the genetic structure of populations of N. americanus in China. Cytochrome oxidase 1 genes were amplified by the polymerase chain reaction, and the sequences compared to those of N. americanus recovered from infected humans from several regions in China. Sequence comparison revealed little difference between the laboratory strain and the field isolates at the cox-1 locus, but also indicated that the laboratory strain is represented by a single cox-1 haplotype. These results suggest that the laboratory strain of N. americanus has undergone a severe genetic bottleneck, and that the genetic diversity in other genes, including potential vaccine antigens, could be similarly limited.

Animals↗
PubMed1999

Epidemiology of human hookworm infections among adult villagers in Hejiang and Santai Counties, Sichuan Province, China.

Hookworm infection as well as other intestinal nematodiases are endemic to Sichuan Province in China. In order to research the prevalence and intensity of these infections we visited two villages in Hejiang County (southern Sichuan Province) and Santai County (northwestern Sichuan Province) between July and October of 1997. Fecal examinations were performed on adult villagers over the age of 15 years (currently children under this age are dewormed annually with anthelmintic drugs). Among 310 residents of Lugao Village (Hejiang County), 87, 63 and 60% were infected with hookworm, Ascaris or Trichuris, respectively. The prevalence of hookworm determined to rise linearly with age (r = 0.97). High intensity infections with hookworm still occur in this region as 22% of the residents have over 3000 eggs per gram (PEG) of feces as determined by quantitative egg counts. The majority of these individuals harbored mixed infection with Necator americanus and Ancylostoma duodenale, although the former predominated when adult hookworms were collected from 30 village residents treated with pyrantel pamoate. In contrast, among the 334 Xinjian villagers examined (Santai County) the majority harbored predominantly light hookworm infections--66.1% of the residents has less than 400 EPG by quantitative fecal examination and only 3.7% exhibited greater than 3000 EPG. Again, N. americanus was the predominant hookworm seen after worm expulsion. We have round that despite economic development which is occurring in some parts of China, significant hookworm infections and clinical hookworm anemia still exist in areas of Sichuan Province. In Hejiang County we found that the intensity of hookworm infection has actually risen within the last 10 years. Hookworm is a medical problem among the elderly in Sichuan.

Adolescent↗
PubMed2006

Hookworm infestation as a risk factor for Mooren's ulcer in South India.

OBJECTIVE: To investigate the association between Mooren's ulcer and intestinal hookworm infestation in South India. DESIGN: Prospective observational case-control study. PARTICIPANTS: Fifteen patients with Mooren's ulcer and 30 age- and gender-matched controls seen at Aravind Eye Hospital. METHODS: Stool samples from the Mooren's ulcer patients and controls were collected and analyzed for presence of hookworm infestation. MAIN OUTCOME MEASURE: Prevalence of hookworm infestation in Mooren's ulcer patients and controls. RESULTS: There was a statistically significant correlation between intestinal hookworm infestation and the occurrence of Mooren's ulcer (P = 0.009). Retrospective exploratory subgroup analyses suggested that the correlation between intestinal hookworm infestation and the occurrence of Mooren's ulcer in men (P<0.0001) was stronger than the correlation in women, with no statistically significant difference being observed in the prevalence of hookworm infestation between women with Mooren's ulcer and female control subjects (P>0.99). Similarly, when both the Mooren's ulcer and the control subject groups were analyzed retrospectively by age > 50 years or age < 50, subjects with an age over 50 demonstrated a stronger correlation between hookworm infestation and Mooren's ulcer than controls (P = 0.017), whereas there was no statistically significant difference in the prevalence of hookworm infection between Mooren's ulcer subjects and control subjects < or = 50 (P = 0.31). CONCLUSION: Intestinal hookworm infestation appears to be associated with the development of Mooren's ulcer in South India. Although the power of our retrospective exploratory subgroup analyses was limited by multiple testing and small sample sizes, these data suggest further that the correlation between intestinal hookworm infestation and the development of Mooren's ulcer may be greatest in male patients with more advanced age.

Adolescent↗
PubMed2004

Human hookworm infection in the 21st century.

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

Ancylostomatoidea↗
PubMed2001

Current prevalence of adult Uncinaria spp. in northern fur seal (Callorhinus ursinus) and California sea lion (Zalophus californianus) pups on San Miguel Island, California, with notes on the biology of these hookworms.

A prevalence survey for hookworms (Uncinaria spp.) was done in northern fur seal (Callorhinus ursinus) and California sea lion (Zalophus californianus) pups on San Miguel Island, CA, in 2000. Intestines of dead pups were examined for adult hookworms in July. These parasites were found in 95% of 20 fur seal pups and 100% of 31 sea lion pups. The number of hookworms varied from 4 to 2142 (mean = 760) in fur seal pups and from 20 to 2634 (mean = 612) in sea lion pups. A direct relationship was evident between body condition and number of hookworms in the pups; that is, pups in poor condition had fewer hookworms than those in good condition. There was a decline in the number of hookworms in sea lion pups in 2000 compared to collections in 1996. Eggs of Uncinaria spp. were found in rectal feces (collected in late September and early October) of none of 35 (0%) live fur seal pups and 41 of 48 (85%) live sea lion pups. Packed cell volume values, determined for most of the same live pups, were essentially normal for C. ursinus but were much lower than normal for most Z. californianus. Hookworm larvae were not found in blubber of fur seal and sea lion pups or in rookery sand in July. Rookery sand, positive for live hookworm larvae when put in a refrigerator, was negative at removal 2.5 years later. The average number of eggs in utero of female hookworms was 285 for three specimens from a fur seal pup and 281 from three specimens from a sea lion pup. One hookworm larva was recovered from milk stripped from the teats of a stranded Z. californianus female at The Marine Mammal Center, Sausalito, CA.

Ancylostomatoidea↗
PubMed2000

Secretory IgA and complement levels in patients with hookworm infection in Zaria.

As a continuing investigation into the immunological reactions involved in hookworm infection the levels of secretory IgA (sIgA). IgM, IgA, complement C3 and C4 were studied in 57 Nigerians with hookworm infection and compared with those of 28 healthy, normal controls. The hookworm patients were divided into three groups based on the degree of anaemia (Hb1-7 and hypochromia +++). Group II had moderate anaemia (Hb8-11, hypochromia ++ and Group III had no signs of anaemia despite the underlying hookworm infection. The patients also comprised those in whom hookworm was the sole infection and those with hookworm associated with other parasites. Significant differences in the results between each patient subgroup and the controls were analysed using the student t-test. IgA was significantly elevated in patients with anaemia of mild to moderate severity and in patients with hookworm only (P < 0.05) while sIgA was significantly elevated in all subgroups compared to controls (P < 0.05). IgM was significantly elevated in-patients with marked anaemia, in-patients without anaemia and in those with hookworm infection associated with other parasites (P < 0.05). The difference in IgG levels between patients and controls was not significant (P 0.1). C4 was significantly elevated in patients with marked moderate anaemia and those with hookworm only (P < 0.05) while C3 levels were not significantly different in the subgroups compared with controls. These results suggest the possibility of polyclonal B-cell activation by T-independent antigens such as the polysaccharide cuticular antigens of the hookworms and the stimulation of the classical pathway of the complement system.

Adolescent↗
PubMed1997

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

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

Adolescent↗