Environmental characteristics around the household and their association with hookworm infection in rural communities from Bahir Dar,Amhara Region,Ethiopia

Soil-Transmitted Helminths (STH) are highly prevalent Neglected Tropical Disease in Ethiopia, an estimated 26 million are infected. Geographic Information Systems and Remote Sensing (RS) technologies assist data mapping and analysis, and the prediction of the spatial distribution of infection in relation to environmental variables. The influence of socioeconomic, environmental and soil characteristics on hookworm infection at the individual and household level is explored in order to identify spatial patterns of infection in rural villages from Zenzelema (Amhara region). Inhabitants greater than 5 years old were recruited in order to assess the presence of STH. Socioeconomic and hookworm infection variables at the household level and environmental variables and soil characteristics using RS were obtained. The dominant STH found was hookworm. Individuals which practiced open defecation and those without electricity had a significant higher number of hookworm eggs in their stool. Additionally, adults showed statistically higher hookworm egg counts than children. Nonetheless, the probability of hookworm infection was not determined by socioeconomic conditions but by environmental characteristics surrounding the households, including a combination of vigorous vegetation and bare soil, high temperatures, and compacted soils (high bulk density) with more acidic pH, given a pH of 6.0 is optimal for hatching of hookworm eggs. The identification of high-risk environmental areas provides a useful tool for planning, targeting and monitoring of control measures, including not only children but also adults when hookworm is concerned.     

Efficacy of different chemotherapeutic schemes for hookworm-infected villagers in China

A comparative analysis has been made of the efficacy of different chemotherapeutic schemes against hookworm infections in China. Hookworm eggs were detected by the improved Kato's thick smear method. Benzimidazole was offered to residents in the tested villages, while NaHCO3 was used as placebo in control villages. Data were analysed by negative binomial distribution with statistic software R2.2.1. In the tested village as a result of the application of selective chemotherapy, hookworm infection rate decreased from 58.79% to 1.08%, while the average of eggs per gram (EPG) reduced from 526.29 to 56.91. The infection rates in the target chemotherapy village and in the mass chemotherapy village declined from 6.90% to 1.92% and 10.10% to 0.65% respectively. It was concluded that the consecutive selective chemotherapy could rapidly decrease the infection rate and EPG of hookworm and maintain the infection rate at low level. The curative effect of the target chemotherapy was similar to that of the mass chemotherapy in the low hookworm endemic area.     

Risk Profiling of Hookworm Infection and Intensity in Southern Lao People’s Democratic Republic Using Bayesian Models

BackgroundAmong the common soil-transmitted helminth infections, hookworm causes the highest burden. Previous research in the southern part of Lao People’s Democratic Republic (Lao PDR) revealed high prevalence rates of hookworm infection. The purpose of this study was to predict the spatial distribution of hookworm infection and intensity, and to investigate risk factors in the Champasack province, southern Lao PDR.MethodologyA cross-sectional parasitological and questionnaire survey was conducted in 51 villages. Data on demography, socioeconomic status, water, sanitation, and behavior were combined with remotely sensed environmental data. Bayesian mixed effects logistic and negative binomial models were utilized to investigate risk factors and spatial distribution of hookworm infection and intensity, and to make predictions for non-surveyed locations.Conclusions/SignificanceHookworm transmission seems to occur within, rather than between villages in Champasack province. We present spatial risk maps of hookworm infection and intensity, which suggest that control efforts should be intensified in the Champasack province, particularly in mountainous areas.     

Ancylostoma ceylanicum infections in humans in Vietnam

Ancylostoma ceylanicum is recognized as the only zoonotic hookworm species that is able to mature into adult stage in the human intestine. While human infections caused by this hookworm species have been reported from neighboring countries and this hookworm is prevalent in dogs in Vietnam, human infection has never been reported in Vietnam. The present study, therefore, aimed to identify human infections with A. ceylanicum in Vietnam. A total of 526 fecal samples from the residents in Long An Province were collected and the presence of hookworm eggs was detected by the Kato-Katz method. The results indicated that the overall prevalence of human hookworm infection was 85/526 (16.2%). After filter paper culture, 3rd stage larvae were successfully obtained from 48 egg-positive samples. The larvae were identified for their species using semi-nested PCR-RLFP on the cox1 gene. As a result, two hookworm species were confirmed; single species infections with Necator americanus or A. ceylanicum, and mixed infections with both species were found in 47.9%, 31.3%, and 20.8% of the samples, respectively.     

The immune response of male DSN hamsters to a primary infection with Ancylostoma ceylanicum

The immune response of hamsters to a chronic hookworm infection has been investigated. Ancylostoma ceylanicum caused long term infections in hamsters which were associated with prominent changes in secondary lymphoid organs. The mesenteric lymph nodes and spleens increased rapidly in size stabilizing at approximately 3-4 times the weight in control animals by weeks 3-7. Cells from both the mesenteric lymph node and spleen, after an initial period of increased blast cell activity, became less reactive in the latter stages of infection. Serum antibody responses were marked, commencing in weeks 3-4 and increasing in intensity throughout the 10 week period of measurement. The results are discussed in relation to their contribution to the understanding of human hookworm infection.     

Epidemiology of hookworm infection in Itagua, Paraguay: a cross sectional study.

A cross-sectional study in Itagua, Paraguay tested 192 people for the presence, intensity and species of hookworm infection. Fifty-nine percent of these individuals were found to be infected. Intensity of infection was determined on 92% of infected individuals by quantitative egg counts. The high intensity hookworm infections, which cause the greatest morbidity, were clustered between the ages of five and 14 years. No differences were seen between genders. The species of hookworm was determined for parasites reared from 72% of infected individuals. Both Necator americanus and Ancylostoma duodenale were identified, although the former species predominated. We conclude that hookworm infection continues to be a public health problem in Paraguay, particularly among children and adolescents who suffer from high intensity infections. A. duodenale continues to persist in the Western Hemisphere and has not been completely displaced by N. americanus.     

'Intervening is representing': medical campaigns that helped identify the prevalence of hookworm

This paper compares anti-hookworm campaigns conducted in the early twentieth century in France, Germany, Brazil and West India. The populations that suffer from hookworm are not identical in the North and in the South. In tropical and semi-tropical regions hookworm is mainly found among poor peasants and is related to lack of hygiene, while in temperate climates hookworm was a professional disease of miners, a highly organized professional segment. Nevertheless, major disparities in the pattern of hookworm control did not reflect the North-South divide, but a difference between campaigns. These aimed at the eradication of hookworm infection (Germany and West-India) and at alleviating the effects of this infection on populations (France and Brazil). Maps that represented the prevalence of hookworm mirrored the aims of the sanitary campaign in which they were used: eradication of parasitic worms versus the reduction of the handicap induced by these worms. In public health as well, representing is intervening. And vice versa: patterns of intervention shape representations.     

Contrasting patterns in the small-scale heterogeneity of human helminth infections in urban and rural environments in Brazil

Marked heterogeneity exists in the patterns of parasitic infection between individuals, households and communities. Analysis of parasite distributions within populations is complicated by the fact that parasite distributions are highly aggregated and few studies have explicitly incorporated this distribution when investigating small-scale spatial heterogeneities. This study aimed to quantify the small-scale (within- and between-household) heterogeneity of helminth infection in an area of Minas Gerais State, Brazil, with rural and urban sectors. Parasitological data from a cross-sectional survey of 1,249 individuals aged 0-86 years from 242 households were analysed. Within-household clustering of infection was assessed using random effect logistic regression models and between-household spatial heterogeneity was assessed using a Bayesian negative binomial spatial model. The overall prevalence of hookworm (Necator americanus) was 66.9%, the prevalence of Schistosoma mansoni was 44.9% and the prevalence of Ascaris lumbricoides was 48.8%. Statistical analysis indicated significant (within) household and (between household) spatial clustering of hookworm in both rural and urban areas and of S. mansoni in rural areas. There was no evidence of either household or spatial clustering of S. mansoni in urban areas. The spatial correlation of S. mansoni was estimated to reduce by half over a distance of 700 m in the rural area. Rural hookworm had a much smaller half-distance (28 m) and urban hookworm showed an even smaller half-distance (12 m). We suggest that such species-specific differences in patterns of infection by environment are primarily due to variation in exposure and parasite life cycle, although host genetic factors cannot be ruled out.     

Spatial heterogeneity of parasite co-infection: Determinants and geostatistical prediction at regional scales

Multiple parasite infections are widespread in the developing world and understanding their geographical distribution is important for spatial targeting of differing intervention packages. We investigated the spatial epidemiology of mono- and co-infection with helminth parasites in East Africa and developed a geostatistical model to predict infection risk. The data used for the analysis were taken from standardised school surveys of Schistosoma mansoni and hookworm (Ancylostoma duodenale/Necator americanus) carried out between 1999 and 2005 in East Africa. Prevalence of mono- and co-infection was modelled using satellite-derived environmental and demographic variables as potential predictors. A Bayesian multi-nominal geostatistical model was developed for each infection category for producing maps of predicted co-infection risk. We show that heterogeneities in co-infection with S. mansoni and hookworm are influenced primarily by the distribution of S. mansoni, rather than the distribution of hookworm, and that temperature, elevation and distance to large water bodies are reliable predictors of the spatial large-scale distribution of co-infection. On the basis of these results, we developed a validated geostatistical model of the distribution of co-infection at a scale that is relevant for planning regional disease control efforts that simultaneously target multiple parasite species.     

An imported human case of hookworm infection with worms in the rectum]

An imported case of rectal hookworm infection was diagnosed by stool examination and recovery of adult worms from the rectal mucosa by sigmoidoscopy. The chief complaints of a patient were diarrhea, abdominal pain and weight loss for about 1 month after returning from his travel abroad to the Southeast Asia. Leukocytosis(16,750/microliters) and peripheral eosinophilia(33.7%) were noticed without anemia. Typical hookworm eggs were detected by stool examination, and 3 worms were collected by sigmoidoscopy from rectal mucosa of this patient. Those worms were confirmed as adult worms of Ancylostoma duodenale(male:1, female:2) based on their morphological characteristics. The symptoms were relieved after treatment with anthelmintics. This case was considered as one of the imported parasitic infections in Korea, and a rare case of hookworm infection on human rectal mucosa.     

Risk factors and spatial patterns of hookworm infection among schoolchildren in a rural area of western Côte d'Ivoire

This study is aimed at investigating the risk factors for hookworm infection among schoolchildren in a rural area of western C?te d'Ivoire and predicting and mapping the spatial distribution of infection. We used demographic and socio-economic data from a cross-sectional survey of 6-16-year-old schoolchildren from 56 schools. Infection with hookworm was determined by microscopic examination of stool samples employing the Kato-Katz technique and an ether-concentration method. Environmental data were derived from satellite images and digitised maps. Bayesian variogram models were applied to investigate the variation of hookworm infection in relation to demographic, socio-economic and environmental factors. The overall hookworm infection prevalence, based on the pooled microscopic diagnoses, was 43.3% and ranged from 5.4 to 79.1% in the schools surveyed. Bivariate analyses showed that sex, age, socio-economic status, elevation, rainfall and land cover were significantly associated with the spatial distribution of hookworm infection. The final multivariate spatial model consisted of the covariates age, sex, socio-economic status, elevation and land cover. When assuming non-stationary underlying spatial dependency, the results of the model suggested that spatial correlation depended on the location only marginally. We conclude that, at the current resolution, it seems more reasonable to target interventions based on well-established epidemiologic risk factors, rather than on spatial factors.     

X-ray structure of Na-ASP-2, a pathogenesis-related-1 protein from the nematode parasite, Necator americanus, and a vaccine antigen for human hookworm infection

Human hookworm infection is a major cause of anemia and malnutrition of adults and children in the developing world. As part of on-going efforts to control hookworm infection, The Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective L3 larval stages of the parasite, including a family of pathogenesis-related (PR) proteins known as the Ancylostoma-secreted proteins (ASPs). A novel crystal structure of Na-ASP-2, a PR-1 protein secreted by infective larvae of the human hookworm Necator americanus, has been solved to resolution limits of 1.68 A and to an R-factor of 17% using the recombinant protein expressed in and secreted by Pichia pastoris. The overall fold of Na-ASP-2 is a three-layer alphabetaalpha sandwich flanked by an N-terminal loop and a short, cysteine-rich C terminus. Our structure reveals a large central cavity that is flanked by His129 and Glu106, two residues that are well conserved in all parasitic nematode L3 ASPs. Na-ASP-2 has structural and charge similarities to chemokines, which suggests that Na-ASP-2 may be an extra-cellular ligand of an unknown receptor. Na-ASP-2 is a useful homology model for NIF, a natural antagonistic ligand of CR3 receptor. From these modeling studies, possible binding modes were predicted. In addition, this first structure of a PR-1 protein from parasitic helminths may shed light on the molecular basis of host-parasite interactions.     

Do hookworms elicit protective immunity in man?

The two main species of human hookworm, Ancylostoma duodenale and Necator americanus (Table 1), are together believed to infect about 900 million people - mainly in tropical countries where adequate sanitary facilities may be lacking. But interactions between the two species, and their relative contributions to observed age-related infection patterns and seasonal cycles of transmission, continue to engender controversy. People tend to remain susceptible to infection through-out life, even with constant exposure to the infective stages. So what role does human immunity or resistance play in the epidemiology and control of infection? In this article, Jerzy Behnke reviews the epidemiology of hookworm infection in the light of current understanding of mechanisms involved in host responses to infection and hookworm evasion of those responses. As he stresses, much further work is required.     

Rates and intensity of re-infection with human helminths after treatment and the influence of individual, household, and environmental factors in a Brazilian community

This study quantifies the rate and intensity of re-infection with human hookworm and Schistosoma mansoni infection 12 months following successful treatment, and investigates the influence of socio-economic, geographical and environmental factors. A longitudinal study of 642 individuals aged over 5 years was conducted in Minas Gerais State, Brazil from June 2004 to March 2006. Risk factors were assessed using interval censored regression for the rate and negative binomial regression for intensity. The crude rate and intensity of hookworm re-infection was 0·21 per year (95% confidence interval (CI) 0·15-0·29) and 70·9 epg (95% CI 47·2-106·6). For S. mansoni the rate was 0·06 per year (95% CI 0·03-0·10) and intensity 6·51 epg (95% CI 3·82-11·11). Rate and intensity of re-infection with hookworm were highest among males and positively associated with previous infection status, absence of a toilet and house structure. Rate and intensity of S. mansoni re-infection were associated with previous infection status as well as geographical, environmental and socio-economic factors. The implications of findings for the design of anti-helminth vaccine trials are discussed.     

Characterising the Mucosal and Systemic Immune Responses to Experimental Human Hookworm Infection

The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-β) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17) response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases.     

Epidemiology of Necator americanus hookworm infections in Xiulongkan Village, Hainan Province, China: high prevalence and intensity among middle-aged and elderly residents

Hookworm is highly endemic to Hainan Province, an island located in the South China Sea. To investigate the prevalence and intensity of infection in the area, the village of Xiulongkan was surveyed between April and July 1998. A cross-sectional study was conducted in which fecal samples of 80% of the village residents (631 individuals) were tested for the presence of helminth eggs. Hookworm was the predominant intestinal helminth in Xiulongkan, where it was determined that 60% of those tested were infected. Necator americanus was the predominant species of hookworm in this population. The prevalence of hookworm increased with age, and then leveled to a plateau for ages 41 yr and up. This observation was in contrast to infections with Ascaris lumbricoides, where the highest prevalences occurred among school-aged children. Women had a significantly higher prevalence of hookworm than men and this difference emerged in early adulthood. The intensity of hookworm infection also significantly increased with age, with the highest intensity infections occurring among middle-aged and elderly residents. Females were more likely to have moderate or heavy infections, whereas males were more likely to have light infections. The rates of hookworm transmission are particularly high among the middle-aged and elderly residents of Xiulongkan.     

Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection

We present immunological data from two clinical trials where the effect of experimental human hookworm (Necator americanus) infection on the pathology of celiac disease was evaluated. We found that basal production of Interferon- (IFN-)γ and Interleukin- (IL-)17A from duodenal biopsy culture was suppressed in hookworm-infected participants compared to uninfected controls. Increased levels of CD4+CD25+Foxp3+ cells in the circulation and mucosa are associated with active celiac disease. We show that this accumulation also occurs during a short-term (1 week) oral gluten challenge, and that hookworm infection suppressed the increase of circulating CD4+CD25+Foxp3+ cells during this challenge period. When duodenal biopsies from hookworm-infected participants were restimulated with the immunodominant gliadin peptide QE65, robust production of IL-2, IFN-γ and IL-17A was detected, even prior to gluten challenge while participants were strictly adhering to a gluten-free diet. Intriguingly, IL-5 was produced only after hookworm infection in response to QE65. Thus we hypothesise that hookworm-induced TH2 and IL-10 cross-regulation of the TH1/TH17 inflammatory response may be responsible for the suppression of these responses during experimental hookworm infection.     

Arthrostoma miyazakiense (Nematoda: Ancylostomatidae) infection in raccoon dogs of Korea and experimental transmission to dogs

Arthrostoma miyazakiense (Nematoda: Ancylostomatidae) is a hookworm species reported from the small intestines of raccoon dogs (Nyctereutes procyonoides) in Japan. Five Korean raccoon dogs (N. procyonoides koreensis) caught from 2002 to 2005 in Jeollanam-do (Province), a southeastern area of South Korea, contained helminth eggs belonging to 4 genera (roundworm, hookworm, whipworm, and Capillaria spp.) and cysts of Giardia sp. in their feces. Necropsy findings of 1 raccoon dog revealed a large number of adult hookworms in the duodenum. These hookworms were identified as Arthrostoma miyazakiense based on the 10 articulated plates observed in the buccal capsule and the presence of right-sided prevulval papillae. Eggs of A. miyazakiense were 60-65 x 35-40 micrometer (av. 62.5 x 35 micrometer), and were morphologically indistinguishable from those of Ancylostoma caninum. The eggs were cultured to infective 2nd stage larvae via charcoal culture, and 100 infective larvae were used to experimentally infect each of 3 mixed-bred puppies. All puppies harbored hookworm eggs in their feces on the 12th day after infection. This is the first report thus far concerning A. miyazakiense infections in raccoon dogs in Korea, and the first such report outside of Japan.     

Hookworm antigens: the potential for vaccination

Hookworms rank with Ascaris as the most prevalent soil-transmitted helminths of man. Up to 1000 million people may be infected. Not all suffer the life-threatening anaemia that reflects heavy burdens of hookworms, but even mild iron-deficiency anaemia due to hookworms can lead to intellectual and growth retardation - especially among infected children. Health education, mass chemotherapy and the sanitary disposal of faeces have been the traditional mainstays of hookworm control, but more recently chemotherapy targeted only to heavily infected individuals who appear predisposed to hookworm anaemia has emerged as a realistic alternative. Ultimately, however, knowledge of the molecular immunology of hookworm infection may provide the basis for rational vaccine development. Although the evidence for acquired immunity to hookworms in man is not strong, work is now underway to identify and to characterize antigens from third and fourth larval stages and adults of Necator americanus and species of Ancylostoma (Table 1). As this article shows, the work provides real promise for improved immunodiagnosis and possible vaccination.