Public engagement for the conduct of a controlled human infection study testing vaccines against Necator americanus (hookworm) in areas of active hookworm transmission in Brazil.

Controlled Human Infection Models (CHIS) involve administering human pathogens to healthy participants in controlled medical settings, which can elicit complex bioethical issues. Understanding how the community perceives such studies can significantly increase the participant's sense of cooperation and increases the researcher's and the participant's transparency. The current study describes the development of an educational intervention to achieve these ends as it aims to (1) analyze perceptions of the Controlled Human Infection Studies (CHIS), and (2) evaluate the participants' comprehension of the CHIS. METHODS: This is a qualitative action research that includes the development of an educational intervention with residents of a rural area in Minas Gerais, Brazil, where there is continuous natural transmission of the human pathogen Necator americanus ("hookworm"). In this area, it is intended to carry out a proposed phase 3 vaccine clinical trial in the future to test the efficacy of hookworm vaccines using controlled human infection. Two data collection strategies were used: an educational intervention and a focus group. RESULTS: The participants' perceptions showed distinct perspectives on CHIS. On one side, they recognized that the investigation is essential for the community, but on the other side, they thought that there would be resistance to its conduct by fear of infection. The idea that the study would generate a benefit for the greater good, contributing to the prevention of hookworm infection, was clearly stated. The participants perceived that the study offered concrete risks that could be reduced by constant monitoring by the researchers. They also mentioned the importance of access to information and the positive influence those who express interest in participating in the study can exert in the community. In relation to comprehension the participants memorized the information, mobilized it to explain everyday situations and created strategies to disseminate the study and engage the community in its development. By repeating and making sense of the information, the participant not only assimilates the knowledge transmitted, but also creates new knowledge. CONCLUSION: We concluded that an educational process of discussion and dialogue around participants' perceptions about the CHIS, promotes understanding and allows ways to disseminate information about the research to be collectively created.

Risk factors for infection with soil-transmitted helminths during an integrated community level water, sanitation, and hygiene and deworming intervention in Timor-Leste.

Water, sanitation and hygiene interventions have been advocated as important complements to deworming programs to improve soil-transmitted helminth control. Evidence for the impact of water, sanitation and hygiene on soil-transmitted helminth infections is mixed, and based mainly on cross-sectional studies. In this study, we assessed associations between individual- and household-level water, sanitation and hygiene variables and soil-transmitted helminth infections, using data collected during the 2 year follow-up study period of the WASH for WORMS randomised controlled trial in Timor-Leste. Data were collected across four surveys, conducted at 6 monthly intervals in 23 communities. We analysed water, sanitation and hygiene and sociodemographic variables as risk factors for infection with Necator americanus, Ascaris spp., and undifferentiated soil-transmitted helminth infection, using generalised linear mixed models to account for clustering at community, household and participant levels. Water, sanitation and hygiene risk factors were examined both concurrently and with a 6 month lag period that coincided with the most recent deworming. The analysis included 2333 participants. Factors associated with N. americanus infection included age group, male sex (adjusted odds ratio (aOR) 3.1, 95% confidence interval (CI) 2.4-4.2), working as a farmer (aOR 1.7, 95% CI 1.2-2.4), and completing secondary school or higher (aOR 0.29, 95% CI 0.16-0.53). Risk factors for Ascaris spp. infection included age group, living in a dwelling with more than six people (aOR 1.6, 95% CI 1.1-2.3), having a tube well or borehole as the household water source (aOR 3.7, 95% CI 1.3-10.8), and using a latrine shared between households 6 months previously (aOR 2.3, 95% CI 1.2-4.3). Handwashing before eating was protective against infection with any soil-transmitted helminth (aOR 0.79, 95% CI 0.65-0.95). In the context of regular deworming, few water, sanitation and hygiene-related factors were associated with soil-transmitted helminth infections. Future research examining the role of water, sanitation and hygiene in soil-transmitted helminth transmission is required, particularly in low transmission settings after cessation of deworming. Identifying improved indicators for measuring water, sanitation and hygiene behaviours is also a key priority.

Restoration of hookworm egg development after prolonged storage in stool suspension.

Hookworm infection is still prevalent in southern Thailand despite control measures. Hookworm eggs submerged for an extended period under water from rainfall or in latrines may not survive, but they may recover their ability to develop into infective larvae when exposed to atmospheric air. This study examined the survival of the hookworm eggs in stool suspension and the restoration of development capability after prolonged storage. In stool mass, eggs developed normally and yielded infective filariform larvae (FL) in 7 days. On the contrary, in 1:10 stool suspension, hookworm eggs were found to remain at the 4-8 cell stage; degenerated eggs were observed after 15 days of storage, and the number of degenerated eggs reached 80 % on day 30. Aeration of the suspension, or transferring to a Petri dish or agar plate, restored the capacity of eggs stored for up to 15 days to develop into FL; thereafter, the capacity declined sharply. Retardation of egg development under water or in stool suspension may be due to a lack of atmospheric air. Use of "night soil" from latrines as fertilizer may be one factor in maintaining hookworm transmission, as worm eggs can undergo normal development upon exposure to atmospheric air.

Integrated school-based surveillance for soil-transmitted helminth infections and lymphatic filariasis in Gampaha district, Sri Lanka.

We explored the practicality of integrating surveillance for soil-transmitted helminthiasis (STH, assessed by Kato-Katz) with transmission assessment surveys for lymphatic filariasis (LF) in two evaluation units (EUs) in Gampaha district, Sri Lanka (population 2.3 million). The surveys were performed 6 years after five annual rounds of mass drug administration with diethylcarbamazine and albendazole. Each transmission assessment survey tested children (N = 1,462 inland EU; 1,642 coastal EU) sampled from 30 primary schools. Low filarial antigenemia rates (0% and 0.1% for the inland and coastal EUs) suggest that LF transmission is very low in this district. The STH rates and stool sample participation rates were 0.8% and 61% (inland) and 2.8% and 58% (coastal). Most STH detected were low or moderate intensity Trichuris trichiura infections. The added cost of including STH testing was ∼$5,000 per EU. These results suggest that it is feasible to integrate school-based surveillance for STH and LF.

Modelling the ecological niche of hookworm in Brazil based on climate.

The distribution of hookworm in schistosomiasis-endemic areas in Brazil was mapped based on climate suitability. Known biological requirements of hookworm were fitted to data in a monthly long-term normal climate grid (18 x 18 km) using geographical information systems. Hookworm risk models were produced using the growing degree day (GDD) water budget (WB) concept. A moisture-adjusted model (MA-GDD) was developed based on accumulation of monthly temperatures above a base temperature of 15 °C (below which there is no lifecycle progression of Necator americanus) conditional on concurrent monthly values (rain/potential, evapotranspiration) of over 0.4. A second model, designated the gradient index, was calculated based on the monthly accumulation of the product of GDD and monthly WB values (GDD x WB). Both parameters had a significant positive correlation to hookworm prevalence. In the northeastern part of Brazil (the Caatinga), low hookworm prevalence was due to low soil moisture content, while the low prevalence in southern Brazil was related to low mean monthly temperatures. Both environmental temperature and soil moisture content were found to be important parameters for predicting the prevalence of N. americanus.

Effects of climatic, socio-economic and behavioural factors on the transmission of hookworm (Necator americanus) on two low-country plantations in Sri Lanka.

The climatic, socio-economic and behavioural factors influencing hookworm (Necator americanus) infection in Sri Lanka were explored between February 2000 and June 2001. In February 2000, a single stool sample was collected from each of the 477 subjects investigated, who were aged 2-74 years (median = 13 years) and lived on the 'lowcountry' Maliboda and Ayr plantations. The 'baseline' prevalence (28.5%) and intensity of hookworm infection (0- 4828.5 eggs/g faeces, with a mean of 128.4 eggs/g) were then determined by examining these initial samples, as Kato-Katz smears. Subsequently, each participant was treated with a single, 500-mg dose of mebendazole and then followed-up, at monthly intervals, for the next 15 months. Whenever a subject was found smear-positive for hookworm eggs at one of the monthly follow-ups, he or she was treated again with mebendazole. This approach allowed the monthly incidence of hookworm infection to be determined for each subject, assuming that subjects became smear-positive approximately 6 weeks post-infection. During the study period, rainfall and mean temperature were recorded daily and then converted to monthly values so that the relationship between the incidence of infection over each month and the rainfall and mean temperature over the same period could be explored. In addition, potentially relevant data on the socio-economic status and behaviour of each subject were collected, in questionnaire-based interviews with the adult subjects and the caregivers of the children investigated. Odds ratios (OR) and their 95% confidence intervals (CI) were then calculated for each factor that might increase the risk of hookworm infection. The monthly incidence of hookworm infection showed three peaks -- in September 2000 (21.3%), January 2001 (20.8%) and May 2001 (17.5%) -- at Maliboda, and two peaks -- in September 2000 (25.0%) and February 2001 (29.2%) -- at Ayr. With the data for all subjects combined, incidence showed a statistically significant correlation with mean temperature (r = -0.468; P = 0.018). The results of a multivariate analysis also revealed that mean temperature was significant (beta = -5.296; P = 0.01) in hookworm incidence. Bathing and washing with water from rock-pools formed by waterfalls (OR = 1.33; CI = 1.35-4.01), the use of wells (OR = 2.35; CI = 1.29-4.30), and a lack of toilets (OR = 1.60; CI = 1.01-2.53) each appeared to increase the risk of hookworm infection significantly. Those living on the two study plantations, and perhaps many other similar plantations in Sri Lanka, would clearly benefit from improved access to the public water supply (especially to pipe-borne water) and toilets.

Hookworm (Necator americanus) transmission in inland areas of sandy soils in KwaZulu-Natal, South Africa.

This study extended the association between hookworm transmission in KwaZulu-Natal and the sandy coastal plain by investigating the parasite's occurrence in isolated areas of sandy soils further inland. A school-based prevalence survey was carried out in selected inland sandy areas and in surrounding areas dominated by clay soils within a narrow altitudinal range of between 500 and 700 m to reduce the effect of altitude on climate-related factors (rainfall and temperature). Sandy areas situated on the coastal plain were included in the analysis for comparative purposes. Soil samples (0-50 mm depth) were collected from each locality to assess their nematode loadings and to analyse selected physical and chemical properties. Significant differences were found between the moderate prevalence of hookworm infection among children living in inland areas with sandy soils (17.3%) and the low prevalence in surrounding non-sandy areas (5.3%, P < 0.001), and between infection among children living in all inland areas (9.3%) and the high prevalence on the coastal plain (62.5%, P < 0.001). Amounts of fine and medium sand were highest in both the coastal plain soils and in inland sandy areas and these fractions showed a significant positive correlation with hookworm prevalence and nematode loadings. Clay, coarse sand and organic matter contents were highest in surrounding non-sandy soils and showed a significant negative correlation with the nematode variables. No statistically significant correlations were found with soil pH at study localities. We conclude that properties of inland sandy soils, particularly particle size distribution, correlate well with hookworm prevalence and nematode loadings and therefore provide a more suitable habitat for nematodes than surrounding non-sandy areas. These results suggest that particle size distribution of sand fractions, organic matter and clay content in the soil influence the survival of hookworm larvae and hence the parasite's transmission.

The role of pigs as transport hosts of the human helminths Oesophagostomum bifurcum and Necator americanus.

We conducted a study in an endemic area of both Oesophagostomum bifurcum and Necator americanus in northern Ghana to examine the possibility of pigs acting as transport hosts for these two human helminth species, due to the commonly observed coprophagic habits of pigs. Under controlled conditions four parasite-free pigs consumed fresh faeces from people heavily infected with both helminths, and faeces were subsequently collected from the rectum of the pigs from 5 to 50 h post-feeding. Four to five per cent of the O. bifurcum and N. americanus eggs fed to the pigs were viable and retrieved as third-stage larvae after coproculture of the pigs' faeces. We discuss the possible impact of the coprophagic habits of pigs as potential parasite transport hosts during different seasons in this area of West Africa.

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.

Transmission patterns and the epidemiology of hookworm infection.

BACKGROUND: This paper presents a suite of models of hookworm transmission dynamics which vary the mixing patterns and rates of contamination and infection between children and adults. In this context mixing refers to the degree of epidemiological communication between children and adults, for example, whether adults are likely to get infected from infective material passed by children. METHODS: Three models are described which represent random mixing, no mixing and restricted mixing respectively. Child, adult and population targeted chemotherapy programmes are examined and compared between these models. Data from a hookworm control programme in Zimbabwe were analysed with respect to their fit to the various models. RESULTS: The analysis suggests that some mixing does occur and that in this study location, the sites where adults deposit faeces are more likely to lead to subsequent contamination than the sites children use. CONCLUSIONS: Mixing patterns may have a profound effect on transmission dynamics and should be considered in relation to design of control programmes.

Gastrointestinal nematodes: the Karkar experience.

This paper reviews our research on the hookworm Necator americanus over several years. Our field site for the research was on Karkar Island, Papua New Guinea, where we found a prevalence of N. americanus infection among adults of nearly 100%. The intensity of infection was related to host age and to the development of iron deficiency anaemia, which occurred at a much lower infection intensity than had been previously reported. We studied the immune response to infection and our results initially suggested that antibody responses and eosinophilia do not protect the host against infection. However, we have more recently found a negative correlation of both IgE and eosinophilia with the weight and fecundity of N. americanus which suggests that the immune response does have some effect on N. americanus and that this immunity is dependent on the Th2 subset of T lymphocytes. Following treatment for hookworm, the prevalence of N. americanus returned almost to pretreatment levels within 2 years, with the rate of acquisition of adult worms independent of host age. A significant predisposition to hookworm infection was demonstrated by individuals. Prevention will result from measures to reduce the transmission and intensity of infection, and can be achieved through improved sanitation or by vaccination. However, vaccination is not yet a viable option because of our limited knowledge about protective immunity.

PIP: Findings are reported from the author's research into the hookworm Necator americanus in the village of Kabasob, Karkar Island, Papua New Guinea, beginning in 1988. N. americanus was determined to be the most prevalent of the identified gastrointestinal nematodes, infesting almost all of the adults with an intensity of 40 worms/host. The intensity of infection was related to host age and to the development of iron deficiency anemia, which occurred at a much lower infection intensity than had been previously reported. Results of an assessment of the immune response to infection initially suggested that antibody responses and eosinophilia do not protect the host against infection. However, the authors have since found a negative correlation of IgE and eosinophilia with the weight and fecundity of N. americanus and that immunity is dependent upon thymus-derived helper 2 lymphocytes. Patients were treated with single 10 mg/kg doses of pyrantel pamoate. However, after 2 years, the prevalence of N. americanus infection had returned almost to pretreatment levels, with the rate of acquisition of adult worms being independent of host age. A highly significant correlation was observed between individuals' pretreatment egg counts and worm burden and those acquired after reinfection. The prevention of infection with N. americanus will come from measures to reduce the transmission and intensity of infection, and can be achieved through improved sanitation or by vaccination. For now, vaccination is not an option because too little is known about protective immunity.

The effect of the availability of latrines on soil-transmitted nematode infections in the plantation sector in Sri Lanka.

The relationship of soil-transmitted nematode infections to the availability of latrines was studied among 1,614 children 3-12 years of age living on plantations in Sri Lanka. The majority (89.7%) of the children had at least one type of soil-transmitted nematode. There was a significantly lower mean count of hookworm eggs for children coming from plantations with good sanitary facilities. For Ascaris and Trichuris, a similar association was observed between the mean egg count and the availability of latrines for children from the low-country plantations, where people live in more scattered settlements, but not in the up-country area, where worker settlements are larger and more crowded. Congested living conditions in themselves consequently seem to be a major determinant for ascariasis and trichuriasis, and the provision of latrines and safe water does not substantially change that situation. However, improvements of sanitary facilities will probably have a more immediate effect on the prevalence of hookworm infection.

Soil-transmitted helminthiases among inhabitants of an oil-palm plantation in West Malaysia.

A total of 819 Indian inhabitants (from 6 months to over 60 years of age) in an oil-palm plantation in West Malaysia was examined for soil-transmitted helminthiases using the brine flotation and Kato thick smear techniques. Half (51.0%) of the inhabitants were found to be infected (33.9% had Ascaris lumbricoides; 36.4% had Trichuris trichiura and 15.6% had Necator americanus). Soil-transmitted helminthiases (both single and mixed infections) were significantly more common among children and young adults from 6 months to 20 years of age where 67.1% (range: 64.7-70.3%) of this age group were infected. The infection rate declined to about 25% or less among elderly people over 50 years of age. Trichuris trichiura was the commonest helminth observed--both as single and mixed infections--and Trichuris mixed with Ascaris was the commonest type of double infection reported. However, there were no significant differences in the distribution of the types of single and double infections among inhabitants of different age groups, nor were there any significant differences in the distribution of soil-transmitted helminthiases among male and female inhabitants. The socioeconomic, environmental and cultural factors contributing to persistently high rates of infection with soil-transmitted helminths among plantation inhabitants are discussed.

Experimental and field studies on the viability of eggs, and the infectivity of third-stage larvae of the human hookworm Necator americanus recovered from the creek waters of the Niger Delta, Nigeria, and their epidemiological significance.

In a combined field and laboratory study, the eggs and 3rd-stage infective larvae of the human hookworm Necator americanus were recovered from the creek waters of the Niger Delta, Nigeria. They were tested for viability and infectivity. Eggs recovered from fresh water creeks showed a viability or hatching index of between 17.5 and 23.7%. Eggs recovered from brackish water showed a viability index of 18.8-21.4% in 'normal' cultures, and a maximum index of 6.3% when cultured in brackish water. The differences in the viability indices of these eggs were not significant (P greater than 0.05). Infective 3rd-stage larvae were recovered from both fresh creek water (205-258 L3/litre of water), and brackish water (45 L3/litre of water). Larvae hatched from brackish water eggs that were cultured in the brackish water were 20% infective by 3 days, but lost all infective potential by 7 days post-hatching. Larvae from fresh water eggs, cultured in fresh water and 'normal' laboratory cultures reached 50% infectivity in 3-5 days, losing potential infectivity in 11-15 days post-hatching. The infectivity patterns of larvae recovered directly from fresh and brackish waters did not differ significantly (P greater than 0.05) from the infectivity patterns of larvae recovered from laboratory cultures of eggs from all the experimental sources. Although larvae recovered directly from fresh and brackish waters survived in these respective media under laboratory conditions, there was a significant difference (P less than 0.05) in their survival patterns. The survival and infectivity rates of field larvae were considerably reduced over time relative to control larvae.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hypotheses on the origin of certain parasites on the Latin American continent]. / Hypothèses sur l'origine de certains parasites du continent latino-américain.

The South American continent has been connected to Africa over millions of centuries. In prehistorical time, the filling of the Bering strait allowed passage on firm ground between Asia and North America. South American peopling has thus occurred from North America, through the Pacific sea and, from the 15th century A.C., through the Atlantic. Necator americanus was present in South America prior to the arrival of black slaves and its African origin is probably related to contacts between Africa and South America; the same applies to Leishmania donovani and Biom-Phalaria glabrata. Ankylostoma duodenale originates from Asia as well as Plasmodium falciparum which was brought by man at time of his migration. To the contrary, muco-cutaneous Leishmaniasis stem (or have a South American origin) from South America. Finally, it is difficult to understand for which reasons Loa loa has not established itself in South America as did Schistosoma mansoni.

Human neonatal infections with hookworms in an endemic area of Southern Nigeria. A possible transmammary route.

Examination of faecal smears of 316 neonates (4-5 weeks old) in a human hookworm endemic area of southern Nigeria showed that 33 (10%) of them were hookworm infected. The majority of the neonatal infections (88%) were due to Ancylostoma duodenale although Necator americanus was the more prevalent hookworm species in the area. The incidence of neonatal infections was pronounced (64%) for mothers who were A. duodenale-positive 5-6 weeks postpartum. A thorough screening of 12.4 litres of colostral milk from all the 316 nursing mothers failed to show the presence of infective hookworm larvae. These results indicate a possibility of a transmammary infection route for the human hookworm A. duodenale.

[Necator americanus uncinariasis in an infant born and residing in Mexico City]. / Uncinariasis por Necator americanus en un lactante originario y residente de la ciudad de México.

A six-month-old infant is reported with the unquestionable diagnosis diagnosis of Necator americanus uncinariasis. The mother was also infected with the same hookworm. The patient was born and has always dwelt in Mexico City, where helminthiasis is considered extremely rare. The epidemiologic studies determined that the dwelling conditions were inadequate for the transmittal of the agent through the soil. The authors emphasize the importance of the presumptive diagnosis in those cases suggesting the disease and to carry out studies to confirm the existence of other infectious means

Transmammary transmission of Necator americanus larva in the human host.

The prevalence of Necator americanus in the 128 nursing mothers at Saraburi hospital was 61%. The examination of milk from these mothers revealed the presence of N. americanus in one case. The finding suggested that milk could be a potential source of hookworm infection in man.