SEARCH

SEARCH BY CITATION

Keywords:

  • hookworm;
  • Ascaris lumbricoides;
  • Schistosoma mansoni;
  • epidemiology;
  • polyparasitism;
  • Brazil
  • ankylostome;
  • Ascaris lumbricoides;
  • Schistosoma mansoni;
  • épidémiologie;
  • polyparasitisme;
  • Brésil
  • Uncinarias;
  • Ascaris lumbricoides;
  • Schistosoma mansoni;
  • epidemiología;
  • poli-parasitismo;
  • Brasil

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

Objective  To identify possible synergistic associations of hookworm and other helminths.

Method  Cross-sectional survey of all households within 10 km2 of Americaninhas, a rural community in Minas Gerais, Brazil. We determined the prevalence and intensity of single and multiple helminth species infection in an age-stratified sample of 1332 individuals from 335 households.

Results  Hookworm was the most prevalent helminth infection (68.2%), followed by Ascaris lumbricoides (48.8%) and Schistosoma mansoni (45.3%). Overall, 60.6% of individuals harboured mixed helminth infections. Multivariate analysis indicated significant positive associations for co-infection with hookworm and S. mansoni and for co-infection with hookworm and A. lumbricoides. Co-infections with hookworm and A. lumbricoides resulted in higher egg counts for both, suggesting a synergistic relationship between these species, although, we found important age differences in this relationship. However, the intensity of S. mansoni or A. lumbricoides co-infection did not differ from that of mono-infection.

Conclusion  These results have implications for the epidemiology, immunology and control of multiple helminth infections. More research is needed to examine the rates of re-infection and immune responses after chemotherapy, and to what extent the effects of polyparasitism are altered by chemotherapy.

Objectif  Identifier les associations synergétiques possibles entre l'ankylostome et les autres helminthes.

Méthode  Une étude transversale incluant toutes les habitations sur 100 km2 autour de Americaninhas, une communauté rurale à Minas Gerais au Brésil. Nous avons déterminé la prévalence et l'intensité de l'infection à une ou plusieurs espèces d'helminthes dans un échantillon d’âge stratifié comportant 1332 individus provenant de 335 habitations.

Résultats  L'ankylostome était l'helminthe le plus prévalant dans les infections (73.3%), suivi du Schistosoma mansoni (45.3%) et Ascaris lumbricoides (48.8%). Au total, 60.6% des individus étaient porteurs d'infections mixtes à helminthes. Une analyse multivariée a indiqué des associations significatives pour la coinfection ankylostome et S. mansoni et pour la coinfection ankylostome et A. lumbricoides. Les coinfections à ankylostome et A. lumbricoides résultaient en un nombre élevé des œufs des deux espèces, quoique nous avons trouvé une différence dans les ages pour cette relation. Cependant, l'intensité de la coinfection avec S. mansoni ou A. lumbricoides ne différait pas de celle de la monoinfection.

Conclusion  Ces résultats ont des implications dans l’épidèmiologie, l'immunologie et le contrôle des infections mixtes aux helminthes. Des recherches plus poussées sont nécessaires pour examiner le taux de réinfection et les réponses immunitaires suite au traitement, et à quel point les effets de polyparasitisme sont altérés par la chemothérapie.

Objetivo  Identificar posibles asociaciones sinergísticas entre uncinarias y otros elmintos.

Método  Estudio de corte transversal de todas las casas dentro de 100 km2 de Americaninhas, una comunidad rural de Minas Gerais, Brasil. Determinamos la prevalencia y la intensidad de infecciones únicas o múltiples en una muestra estratificada por edad de 1332 individuos provenientes de 335 hogares.

Resultados  Las uncinarias fueron la infección helmíntica más prevalente (73.3%), seguidas por Schistosoma mansoni (45.3%) y Ascaris lumbricoides (48.8%). En total, 60.6% de los individuos portaban infeciones helminticas mixtas. El análisis multivariado indica una asociación positiva para la co-infección con uncinarias y S. mansoni así como para la co-infección con uncinarias y A. lumbricoides. Co-infecciones con uncinarias y A. lumbricoides resultaban con conteos de huevos más altos para ambos, sugiriendo una relación sinergística entre estas dos especies, aunque encontramos diferencias en edad importantes en esta relación. Sin embargo, la intensidad de co-infección de S. mansoni o A. lumbricoides no se diferenciaba de la de la mono-infección.

Conclusión  Estos resultados tienen implicaciones en la epidemiología, inmunología y el control de infecciones helmínticas múltiples. Es necesario realizar más estudios para determinar las tasas de re-infección y respuesta inmune después de recibir quimioterapia, así como para averiguar hasta que punto los efectos del poli-parasitismo son alterados por la quimioterapia.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

In 1978, Buck and colleagues published a landmark study of polyparasitism in rural communities in Chad, Peru, Afghanistan and Zaire, which indicated the frequent occurrence of concomitant parasitic infections (Buck et al. 1978). An increasing number of studies of helminth epidemiology have since shown that multiple helminth infections are extremely widespread (Booth et al. 1998; Needham et al. 1998; Petney & Andrews 1998; Brooker et al. 2000; Howard et al. 2002; Tchuem Tchuentéet al. 2003; Raso et al. 2004). Evidence from laboratory model systems suggests that infection with one helminth may influence the outcome of infection with others (Cox 2001), with evidence suggestive of both synergism and antagonism in concurrent intestinal nematode and schistosome infections (Pritchard et al. 1991; Webster et al. 1997; Corrêa-Oliveira et al. 1988,2002; Cox 2001). A number of epidemiological studies have indicated that individuals with multiple helminth infections often harbour heavier infections than individuals with single species infections (Booth et al. 1998; Needham et al. 1998; Brooker et al. 2000; Tchuem Tchuentéet al. 2003). Other studies have reported that hookworm infection is positively associated with Schistosoma mansoni infection (Chamone et al. 1990; Keiser et al. 2002a,b; Raso et al. 2004) and with filarial nematode infection (Faulkner et al. 2005). It has also been speculated that helminth infections may adversely influence host immune responses to other parasites, especially to intracellular pathogens such as malaria (Nacher 2004). To date, most studies of polyparasitism have been undertaken among populations of school-aged children. To our knowledge, there have been only three epidemiological studies, which have investigated multiple helminth infections, both in terms of prevalence and intensity, within an entire community (Buck et al. 1978; Keiser et al. 2002b; Raso et al. 2004). Here, we present age-stratified data from an ongoing longitudinal study of the epidemiology and immunology of intestinal nematode and schistosome infections in Brazil. The present analysis describes the epidemiology of single and multiple helminth infection. Emphasis is placed on age-related changes in polyparasitism and with associations that occur between the species.

Materials and methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

The study was reviewed and approved by the ethical committee of the Centro de Pesquisas René Rachou-FIOCRUZ and the National Committee for Ethics in Research (Brazil), and the ethical review boards of George Washington University (USA) and London School of Hygiene and Tropical Medicine (UK).

Study area and population

The study was conducted in Americaninhas in Minas Gerais State of southeastern Brazil. It is located in the northeast of the state, lying between 17°02′12.310′′– 17°13′13.857′′ S and 41°20′18.334′′– 41°07′39.737′′ W and is divided into five rural sectors and a central municipality. The Fundação National de Saude (the National Health Foundation) estimates 1000 people living in the urban municipal centre and another 1000 in the surrounding rural areas. The area is hilly and characterized by a tropical altitude climate, with an average temperature of 24 °C, and experiences a long rainy season between November and March; annual rainfall is 1300–2000 mm. The majority of inhabitants are involved in rural subsistence farming, growing mainly coffee, manioc and beans. Cattle ranching is another important source of income. Houses are predominantly made from concrete or from a combination of wood and mud and have either tiles or iron sheets for roofing. Only approximately 50% of these homes have a latrine and people commonly collect their water from local springs. There is only one health post in the area with two auxiliary health workers who are paid by the municipality.

Recruitment

The study area of Americaninhas is located in the municipality of Nova Oriente, NE, Minas Gerais State, Brazil. The household was the main sampling unit, with the research team visiting all houses within 10 km2 of the study site to obtain informed consent using a written and verbal consent form approved by the National Ethics Committee of Brazil, the Internal Review Board, Centro de Pesqusias René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil, and the Internal Review Board, George Washington University Medical Center, Washington DC, USA. A series of meetings were held with community members to explain the purpose and method of the study, that participation was voluntary, and that they were able to withdraw from the study at any time. Written consent was obtained from all adult subjects and from parents or guardians of minors. Each house was assigned a unique household identification number (HHID), and each resident a unique personal identity number (PID). Only individuals meeting the following inclusion criteria were included into the study: (1) resident in the study area over the last 24 months; (2) reporting not to have received anthelmintic treatment within the last 24 months; and (3) willing and able to give informed consent to study protocol. Individuals were not included if they: (1) attended school outside the study area; (2) worked full-time outside the study area; or (3) tested positive on a pregnancy test. Females found to be pregnant during the test were excluded from treatment during their pregnancy and received treatment for all helminth infections later. The results of these tests were made available to the individual only upon request and not to family members.

Parasitology

Participating household members were informed 24 h in advance about the start of the stool sample collection and plastic containers were provided. Containers were labeled with the participant's full name, age, PID, HHID, and day of distribution. Participants were instructed to deposit one faecal sample per day into each container and return the container immediately to one of several collection points, where the sample was stored at 4 °C. Faecal samples returned later than 48 h after date of distribution were not accepted, and new containers were issued. Presence of infection was determined by using the formalin-ether sedimentation technique. Individuals positive for any helminth in the formalin-ether sedimentation technique were asked to contribute two more samples over the course of two more days to be analyzed by Kato-Katz technique for assessment of eggs per gram of faeces (infection intensity). Two slides were taken from each day's faecal sample for a total of four slides from each individual. Slides were examined within 45 min of slide preparation to avoid clearing of hookworm eggs. The arithmetic means of the fours slides was calculated and then transformed according to the Kato-Katz method (Katz et al. 1972). Three methods were used to ensure standardization in the preparation and reading of slides: (i) the same technicians prepared and read all slides; (ii) both technicians read every tenth set of slides, with the results compared (r = 0.89; P < 0.001); (iii) the coefficient of variation for egg counts was assessed over the 2 days. A coefficient of variation above 20% was considered unacceptable (n = 14 individuals), and the participants asked to volunteer two more faecal samples until the coefficient of variation over 2 days was below 20%. While evidence indicated the predominance of Necator americanus over Ancylostoma duodenale in Brazil (Goncalves et al. 1990; Kobayashi et al. 1995; Geiger et al. 2004), we examined faeces for expelled worms on three consecutive days from patients who had been treated with albendazole. The worms were washed in phosphate-buffered saline (PBS) and stored in 70% ethanol. For determination of the species, the worms were rinsed in a phenol solution (70%) and the mouthparts were examined under the microscope (400× magnification). A total number of 120 male and female worms were determined to be exclusively of the species N. americanus.

Data analysis

Intensity of helminth infection was expressed as arithmetic means. This is justified biologically since intensity of infection is assumed to proportional to clinical outcomes and no saturation occurs at high intensities. For example, intensity of hookworm infection is proportional to faecal blood loss (Stoltzfus et al. 1996) and intensity of S. mansoni is proportional to periportal fibrosis. This is also justified statistically since geometric means, despite reducing the skewness of a distribution, can be biased estimators of the true population mean and give misleading indicators of the differences between groups (Fulford 1994). Definitions of heavy infection were based on thresholds of egg counts proposed by WHO: hookworm 4000 eggs/gram faeces; A. lumbricoides 50,000 eggs/gram faeces; and S. mansoni 400 eggs/gram faeces (WHO 2002). The prevalence of multiple species infection was stratified by four age classes: 0–9, 10–24, 25–39 and 40+ years. These categories were chosen to reflect the age intensity profiles (Figure 1). Expected prevalences of multiple species infections were estimated based on a simple probabilistic model, which uses overall prevalence data (Booth & Bundy 1995), and differences tested using a Chi-square test. Associations between different helminth species were investigated using a random effects logistic regression modelling. A full model was developed, forcing age group, sex and sector, as well as presence of other infections, into the model. Separate models were developed for any infection and for heavy infections. Interactions between individual species and sex and age group were tested for first and removed if non-significant (P > 0.05). Models were adjusted to account for non-independence of observations within households. Due to the marked skewness of egg counts, Kruskal–Wallis tests were used to assess the variation of egg counts by multiple species infection, stratified by age group. Analysis was undertaken using Stata 8.2 (College Station, TX, USA).

image

Figure 1. Age-prevalence and-intensity curves for helminth infection among 1332 individuals in Americaninhas, Minas Gerais, Brazil 2004. (a) A. lumbricoides, (b) S. mansoni and (c) hookworm. Solid line indicates prevalence and dashed line indicates intensity of infection.

Download figure to PowerPoint

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

A total of 1332 individuals from 335 households were included in the study, of these individuals 82.7% were infected with at least one species of helminth. The overall prevalence of hookworm infection was 68.2%, the prevalence of S. mansoni was 45.3%, the prevalence of A. lumbricoides was 48.8%, the prevalence of Trichuris trichiura was 1.1% and the prevalence of infection of Enterobius vermicularis, Hymenolepis nana and Taenia spp. were respectively, 0.8%, 0.2% and 0.2%. The prevalence of heavy hookworm infection was 8.3%, the prevalence of heavy S. mansoni infection was 8.1%, and the prevalence of heavy A. lumbricoides infection was 18.2%.

Prevalence and intensity of A. lumbricoides rose to a peak in the 5–10 years age group and declined thereafter (Figure 1a). Prevalence of hookworm infection rose with age until the 15–20 years age group and stayed constant thereafter. Prevalence of S. mansoni infection also rose with age until the 10–15 years age group where it remained constant until peaking in the 40–45 years age group. Intensity of S. mansoni infection peaked in the 10–15 years age group and again in the 20–25 years age group and declined thereafter, whereas intensity of hookworm infection rose with increasing age (Figure 1b, c).

The prevalence of single and multiple species infection overall and by age group is shown in Table 1. Overall, of those infected with a helminth, 73.3% of individuals harboured mixed infections. The most common combinations were infection with hookworm and A. lumbricoides and with hookworm and S. mansoni. Only 4.6% of infected individuals were concurrently infected with A. lumbricoides and S. mansoni, which was significantly lower than would be expected by chance alone (6.5%) (χ2 = 9.9, P = 0.001). The observed percentage of individuals with all three species of infection was 19%, significantly higher than the expected value of 13.8% (χ2 = 13.0, P = 0.0003), and the prevalence of dual infection with hookworm and A. lumbricoides was also significantly higher than expected by chance (19.9%vs. 16.7%, χ2 = 4.6, P = 0.03). The prevalences of different species combinations are shown to vary by age. Table 2 presents the results of the logistic regression analysis and shows that, while controlling for age-group, sex and sector, hookworm was significantly positively associated with A. lumbricoides and with S. mansoni. This was true both for infections per se and for heavy infections. In contrast, no significant associations were observed between co-infections A. lumbricoides and S. mansoni.

Table 1.  Observed and expected prevalence of single and multiple helminth infection among 1332 individuals in Americaninhas, Minas Gerais, Brazil in 2004.
Species combinationNumber positivePercentage of infectionsPercentage of populationχ2P valueObserved by age groups (years)
ObservedExpected0–910–2425–3940+
Any single infection29426.722.1   24.819.818.724.2
Hookworm only15213.811.420.641.6<0.00018.810.711.615.2
A. lumbricoides only817.46.17.83.10.08012.44.31.53.9
S. mansoni only615.54.68.013.4<0.00013.64.85.65.1
Any double infection55450.341.6   37.648.939.338.9
Hookworm and A. lumbricoides26524.119.916.74.60.0326.222.712.113.8
Hookworm and S. mansoni23821.617.917.10.30.6106.021.424.223.9
A. lumbricoides and S. mansoni514.63.86.59.90.0015.44.83.01.2
Triple infection25323.019.013.813.00.000316.122.119.717.9
Any mixed infection80773.360.6   53.771.059.056.8
Table 2.  Associations between helminth species among 1332 individuals in Americaninhas, southeastern Brazil in 2004.
ParasiteAssociationAdjusted OR (95% CI)*P-value
  1. * OR = Odds ratio for infection adjusted by age group, sex and presence of other infections, and clustering by household; CI = Confidence Interval.

HookwormA. lumbricoides3.59 (2.67, 4.82)<0.001
S. mansoni2.95 (2.19, 3.98)<0.001
Heavy hookwormHeavy A. lumbricoides2.29 (1.35, 3.90) 0.002
Heavy S. mansoni4.13 (2.43, 6.99)<0.001
A. lumbricoidesHookworm3.65 (2.71, 4.91)<0.001
S. mansoni0.99 (0.75, 1.29) 0.917
Heavy A. lumbricoidesHeavy hookworm2.29 (1.34, 3.92) 0.002
Heavy S. mansoni0.59 (0.32, 1.11) 0.105
S. mansoniHookworm3.01 (2.22, 4.06)<0.001
A. lumbricoides0.98 (0.75, 1.28) 0.881
Heavy S. mansoniHeavy hookworm4.19 (2.45, 7.14)<0.001
Heavy A. lumbricoides0.59 (0.32, 1.09) 0.091

Overall, the mean intensity of hookworm infection significantly increased according to the multiplicity of species infection: hookworm only = 1220 epg; hookworm and A. lumbricoides = 1827 epg; hookworm and S. mansoni = 1888 epg; all three species = 2023 epg (P = 0.0002). Intensity of A. lumbricoides also significantly differed by multiple species infections, with individuals infected with A. lumbricoides and S. mansoni harbouring the lightest infections: A. lumbricoides only = 6323 epg; A. lumbricoides and hookworm and = 6551 epg; A. lumbricoides and S. mansoni = 4304 epg; all three species = 5330 epg (P = 0.003). Individuals infected with A. lumbricoides and S. mansoni also had the lowest intensities of S. mansoni, although group differences had only borderline significance: S. mansoni only = 208 epg; S. mansoni and hookworm = 338 epg; S. mansoni and A. lumbricoides = 163 epg; all three species = 266 epg (P = 0.07). When investigating these patterns by age group important differences were revealed. Although, mono-infected individuals had lower hookworm intensities in each age group, hookworm intensity differed significantly by species combinations only in the age categories 10–24 and 25–39 years (Kruskall–Wallis test of equality of populations: P = 0.027 and P = 0.015) (Figure 2c). Similarly, although individuals infected with S. mansoni and A. lumbricoides had the lowest intensity of A. lumbricoides infection, intensity only differed by species combinations among 25–39 years old (P = 0.009) (Figure 2b). For A. lumbricoides there were no significant differences in intensity by species combinations between the age groups, although individuals infected with S. mansoni and A. lumbricoides consistently had the lowest intensities (Figure 2a).

image

Figure 2. Mean intensity of infection among 1332 individuals in Americaninhas, Minas Gerais, Brazil, stratified by multiplicity of infection and age group. (a) A. lumbricoides, (b) S. mansoni and (c) hookworm. Columns indicate arithmetic mean intensity of infection and vertical bars indicate standard error of the mean.

Download figure to PowerPoint

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

In the tropics it is common for a single individual to be infected with several parasite species at the same time (Brooker et al. 2000; Tchuem Tchuentéet al. 2003; Raso et al. 2004; Faulkner et al. 2005). Here, we show that, among all age groups, co-infection with schistosomes and intestinal nematodes is extremely common in rural Brazil. This finding confirms those studies conducted among school-aged children (Booth et al. 1998; Needham et al. 1998; Brooker et al. 2000; Tchuem Tchuentéet al. 2003; Faulkner et al. 2005).

Our analysis showed that there was a significant positive association between co-infection with hookworm and S. mansoni and with hookworm and A. lumbricoides. The positive association for co-infection with hookworm and S. mansoni is in keeping with previous studies in Brazil (Chamone et al. 1990) and Côte d'Ivoire (Keiser et al. 2002a,b; Raso et al. 2004). We further show that intensity of hookworm infection typically increased with the multiplicity of infection. Taken together, these results suggest a synergistic relationship between hookworm and other helminths, as has been observed elsewhere (Chamone et al. 1990). This observation is also compatible with immunological data from hookworm patients showing that antibodies reacting with crude antigen extracts from hookworms cross-react with egg and adult worm antigen extracts from S. mansoni (Pritchard et al. 1991; Corrêa-Oliveira et al. 1988, 2002). Similar antibody cross-reactivity between N. americanus and S. mansoni has been observed in murine models (Timothy et al. 1992). However, even though antigenic cross-reactivity was reported in this experimental model, no protective immunity was achieved by heterologous challenge infection (Timothy et al. 1992). Corrêa-Oliveira et al. (1988,2002) found that individuals from areas co-endemic for S. mansoni and hookworm had significantly lower proliferative responses to crude hookworm antigen extracts than individuals from hookworm mono-endemic areas.

Immunological mechanisms, such as the differential activation of T helper cell subsets by parasitic stages, may explain the synergisms and antagonisms observed during helminth co-infections in this study. Mice with an underlying S. mansoni infection were found to have a T helper 2-dominant immune response that could alter the disease outcome of different intestinal nematode species, e.g., Strongyloides venezuelensis (Yoshida et al. 1999) and T. muris (Curry et al. 1995). Protective effects might vary between different parasitic species, acting at different sites (skin, lung and gut) and different developmental stages such as third stage infective larvae (L3) (Yoshida et al. 1999) or adult worms (Curry et al. 1995). In N. americanus infection, increased levels of interleukin (IL)-5 secreted by peripheral blood mononuclear cells upon stimulation with crude adult hookworm antigen extract correlated with resistance to reinfection, indicating a role for Th2 cytokine responses in protection against hookworm reinfection (Quinnell et al. 2004a).

Interestingly, individuals in our study co-infected with hookworm and other strong Th2 cytokine (including IL-5) inducing helminth such as A. lumbricoides or S. mansoni had higher intensities of infection than individuals mono-infected with hookworm, pointing to a possible synergistic effect on the immune response to these helminths during hookworm co-infection. As such, it is possible that co-infection with hookworm, with a reduced cellular reactivity (Corrêa-Oliveira et al. 2002) and the secretion of immunomodulatory molecules (Chow et al. 2000; Loukas & Prociv 2001; Hsieh et al. 2004), subverts or overrides the mechanisms which would enable an age-acquired decline in infection intensity seen in other helminth infections. In this context, it is important to mention the possible role of recently described T-regulatory cells (Tr1), and their secretion of downmodulatory cytokines, e.g. IL-10 or TGF-β, which seem to participate in the regulation of the host's immune response (Maizels et al. 2004). For experimental schistosomiasis, these T-regulatory cells were found to be the major source of IL-10 (Hesse et al. 2004). Whether the observed production of IL-10 is stimulated directly by the presence of the parasites and/or their products, or represents a natural cross-regulatory mechanism initiated by the host remains to be established.

Here we also show that that individuals co-infected with A. lumbricoides and S. mansoni have lower infection intensities for each species than individuals mono-infected with each species, suggestive of antagonism between A. lumbricoides and S. mansoni infection. Previous studies of A. lumbricoides infections in humans have shown that Th-2-type immune responses were associated with reduced worm burden and age-related protective immune responses (Turner et al. 2003). A similarly strong induction of Th-2 responses has been observed with the start of S. mansoni egg deposition in intestinal tissues in experimental animal models (Grzych et al. 1991; Pearce et al. 1992). As such, this markedly similar immune modulation may account for the decrease in intensity of infection observed in individuals co-infected with S. mansoni and A. lumbricoides compared to individuals mono-infected with each helminth. This has also been proposed for experimental infections with A. suum (Frontera et al. 2003). However, many other factors may also contribute to these parasite interactions as well, and we plan to further investigate the immune responses of individuals who are mono- and co-infected for hookworm, A. lumbricoides, and S. mansoni in future studies.

An alternative explanation for the observed associations is the similar and different transmission routes of the different helminth species. Transmission of hookworm and A. lumbricoides occurs through exposure to soil contaminated with free-living infective stages and is influenced by several factors, including micro-climatic suitability, sanitation and hygiene, and environmental contamination with human excreta (Olsen et al. 2001; Keiser et al. 2002a; Traub et al. 2004). Schistosomiasis, in contrast, is a water-borne infection and transmission is based on infective water bodies and human water contact. Information on individual and household specific risk factors was not collected and this hypothesis remains to be further investigated.

In the tropics polyparasitism is extremely common. Our results show that infection with one helminth can profoundly affect the intensity of infection with another helminth, e.g., heavy hookworm infection results in heavy infection with S. mansoni and vice versa. It may be that the powerful immunomodulatory mechanisms of helminths have important effects on susceptibility not only to other helminth infections but to other infectious diseases in general, including implication for the response to vaccination: e.g., the response to Bacillus Calmette-Guerin (BCG) vaccination in the tropics (Elias et al. 2001; Brooker et al. 2004; Quinnell et al. 2004b) and the live oral cholera vaccine CVD 103-HgR (Cooper et al. 2001). Our cross-sectional study provides an indication of the presumably cumulative effect of single and multiple species infection. Longitudinal studies are now underway in the study area to examine the rates of re-infection and immune responses following chemotherapy, and thus will provide information on how much of the effects of polyparasitism is altered by chemotherapy.

Acknowledgement

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

We are very grateful to inhabitants of Americaninhas who kindly participated in the study. We are also most appreciative of the hard work of all of the field staff, which made this analysis possible, and deserve many thanks. Fieldwork was financially supported by the Human Hookworm Vaccine Initiative (HHVI) of the Sabin Vaccine Institute, and the Bill and Melinda Gates Foundation. SB is supported by a Wellcome Trust Advanced Training Fellowship (073656), JB is supported by an International Research Scientist Development Award (IRSDA) (K01 TW00009) from the John E. Fogarty International Center, NIH, and FF was supported by a Chadwick Trust travel award.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References
  • Booth M & Bundy DAP (1995) Estimating the number of multiple-species geohelminth infections in human communities. Parasitology 111, 645653.
  • Booth M, Bundy DAP, Albonico M, Chwaya H & Alawi K (1998) Associations among multiple geohelminth infections in schoolchildren from Pemba Island. Parasitology 116, 8593.
  • Brooker S, Miguel E, Moulin S, Luoba A, Bundy D & Kremer M (2000) Epidemiology of single and multiple species of helminth infections among school children in Busia District, Kenya. East African Medical Journal 77, 157161.
  • Brooker S, Bethony J & Hotez PJ (2004) Human hookworm infection in the 21st century. Advances in Parasitology 58, 197288.
  • Buck AA, Anderson RI & MacRae AA (1978) Epidemiology of poly-parasitism: I. Occurrence, frequency, and distribution of multiple infections in rural communities in Chad, Peru, Afghanistan, and Zaire. Annals of Tropical Medicine and Parasiology 29, 6170.
  • Chamone M, Marques CA, Atuncar GS, Pereira AL & Pereira LH (1990) Are there interactions between schistosomes and intestinal nematodes? Transactions of the Royal Society of Tropical Medicine and Hygiene 84, 557558.
  • Chow SC, Brown A & Pritchard D (2000) The human hookworm pathogen N. americanus induces apoptosis in T lymphocytes. Parasite Immunology 22, 2129.
  • Cooper PJ, Chico M, Sandoval C et al. (2001) Human infection with Ascaris lumbricoides is associated with suppression of the interleukin-2 response to recombinant cholera toxin B subunit following vaccination with the live oral cholera vaccine CVD 103-HgR. Infection and Immunity 69, 15741580.
  • Corrêa-Oliveira R, Dusse LM, Viana IR, Colley DG, Santos Carvalho O & Gazzinelli G (1988) Human antibody responses against schistosomal antigens. I. Antibodies from patients with Ancylostoma, Ascaris lumbricoides or Schistosoma mansoni infections react with schistosome antigens. American Journal of Tropical Medicine and Hygiene 38, 348355.
  • Corrêa-Oliveira R, Golgher DB, Oliveira GC et al. (2002) Infection with Schistosoma mansoni correlates with altered immune responses to Ascaris lumbricoides and hookworm. Acta Tropica 83, 123132.
  • Cox FEG (2001) Concomitant infections, parasites and immune responses. Parasitology 122, S23S38.
  • Curry AJ, Else KJ, Jones F, Bancroft A, Grencis RK & Dunne DW (1995) Evidence that cytokine-mediated immune interactions induced by Schistosoma mansoni alter disease outcome in mice concurrently infected with Trichuris muris. The Journal of Experimental Medicine 181, 769774.
  • Elias D, Wolday D, Akuffo H, Petros B, Bronner U & Britton S (2001) Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guerin (BCG) vaccination. Clinical & Experimental Immunology 123, 219225.
  • Faulkner H, Turner J, Behnke J et al. (2005) Associations between filarial and gastrointestinal nematodes. Transactions of the Royal Society of Tropical Medicine and Hygiene 99, 301312.
  • Frontera A, Carron A, Serrano FJ, Roepstorff A, Reina D & Navarrete I (2003) Specific systemic IgG1, IgG2 and IgM responses in pigs immunized with infective eggs or selected antigens of Ascaris suum. Parasitology 127, 291298.
  • Fulford AJ (1994) Dispersion and bias: can we trust geometric means? Parasitology Today 10, 446448.
  • Geiger SM, Massara CL, Bethony J, Soboslay PT & Correa-Oliveira R (2004) Cellular responses and cytokine production in post-treatment hookworm patients from an endemic area in Brazil. Clinical and Experimental Immunology 136, 334340.
  • Goncalves JF, Tanabe M, Medeiros F de P et al. (1990) Parasitological and serological studies on amoebiasis and other intestinal parasitic infections in the rural sector around Recife, northeast Brazil. Revista do Instituto de Medicina Tropical de Sao Paulo 32, 428435.
  • Grzych JM, Pearce EJ, Cheever A et al. (1991) Egg deposition is the major stimulus for the production of Th 2 cytokines in murine schistosomiasis mansoni. Journal of Immunology 146, 13221327.
  • Hesse M, Piccirillo CA, Belkaid Y et al. (2004) The pathogenesis of schistosomiasis is controlled by cooperating IL-10-producing innate effector and regulatory T cells. Journal of Immunology 172, 31573166.
  • Howard SC, Donnelly CA, Kabatereine NB, Ratard RC & Brooker S (2002) Spatial and intensity-dependent variations in associations between multiple species helminth infections. Acta Tropica 83, 141149.
  • Hsieh GC-F, Loukas A, Wahl AM et al. (2004) A secreted protein from the human hookworm N. americanus binds selectively to NK cells and induces IFN-γ production. Journal of Immunology 173, 26992704.
  • Katz N, Chaves A & Pelligrino J (1972) A simple device for quantitative stool thick-smear technique in schistosomiasis mansoni. Revue Instituto Medicina Tropical 14, 817820.
  • Keiser J, N'Goran EK, Singer BH, Lengeler C, Tanner M & Utzinger J (2002a) Association between Schistosoma mansoni and hookworm infections among schoolchildren in Cote d'Ivoire. Acta Tropica 84, 3141.
  • Keiser J, N'Goran EK, Traore M et al. (2002b) Polyparasitism with Schistosoma mansoni, geohelminths, and intestinal protozoa in rural Cote d'Ivoire. Journal of Parasitology 88, 461466.
  • Kobayashi J, Hasegwa H, Forli AA et al. (1995) Prevalence of intestinal parasitic infection in five farms in Holambra, São Paulo. Revista do Instituto de Medicina Tropical de Sao Paulo 37, 1318.
  • Loukas A & Prociv P (2001) Immune responses in hookworm infections. Clinical Microbiology Review 14, 689703.
  • Maizels RM, Balic A, Gomez-Escobar N, Nair M, Taylor MD & Allen JE (2004) Helminth parasites-masters of regulation. Immunology Reviews 201, 89116.
  • Nacher M (2004) Interactions between worm infections and malaria. Clinical Reviews in Allergy Immunology 26, 8592.
  • Needham C, Kim HT, Hoa NV et al. (1998) Epidemiology of soil-transmitted nematode infections in Ha Nam Province, Vietnam. Tropical Medicine and International Health. 3, 904912.
  • Olsen A, Samuelsen H & Onyango-Ouma W (2001) A study of risk factors for intestinal helminth infections using epidemiological and anthropological approaches. Journal of Biosocial Science 38, 569584.
  • Petney TN & Andrews RH (1998) Multiparasite communities in animals and humans: frequency, structure and pathogenic significance. International Journal of Parasitology 28, 377393.
  • Pearce EJ, Caspar P, Grzych JM, Lewis FA & Sher A (1992). Downregulation of Th 1 cytokine production accompanies induction of Th 2 responses by a parasitic helminth Schistosoma mansoni. The Journal of Experimental Medicine 173, 159162.
  • Pritchard DI, Quinnell RJ, McKean PG et al. (1991) Antigenic cross-reactivity between N. americanus and Ascaris lumbricoides in a community in Papua New Guinea infected predominantly with hookworm. Transactions of the Royal Society of Tropical Medicine and Hygiene 85, 511514.
  • Quinnell RJ, Pritchard DI, Raiko A, Brown AP & Shaw MA (2004a) Immune responses in human necatoriasis: association between interleukin-5 responses and resistance to reinfection. Journal of Infectious Diseases 190, 430438.
  • Quinnell RJ, Bethony J & Pritchard DI (2004b) The immunoepidemiology of human hookworm infection. Parasite Immunology 26, 443454.
  • Raso G, Luginbuhl A, Adjoua CA et al. (2004) Multiple parasite infections and their relationship to self-reported morbidity in a community of rural Cote d'Ivoire. The International Journal of Epidemiology 33, 10921102.
  • Stoltzfus RJ, Albonico M, Chwaya HM et al. (1996) Hemoquant determination of hookworm-related blood loss and its role in iron deficiency in African children. American Journal of Tropical Medicine and Hygiene 55, 399404.
  • Tchuem Tchuenté LA, Behnke JM, Gilbert FS, Southgate VR & Vercruysse J (2003) Polyparasitism with Schistosoma haematobium and soil-transmitted helminth infections among school children in Loum, Cameroon. Tropical Medicine and Internationl Health 8, 975986.
  • Timothy LM, Coulson PS, Behnke JM & Wilson RA (1992). Cross-reactivity between N. americanus and Schistosoma mansoni in mice. International Journal of Parasitology 22, 11431149.
  • Traub RJ, Robertson ID, Irwin P, Mencke N & Andrew Thompson RC (2004) The prevalence, intensity and risk factors associated with geohelminth infection in tea-growing communities of Assam, India. Tropical Medicine and International Health 9, 688701.
  • Turner JD, Faulkner H, Kamgno J et al. (2003) Th 2 cytokines are associated with reduced worm burdens in a human intestinal helminth infection. Journal of Infectious Diseases 188, 17681775.
  • Webster M, Correa-Oliveira R, Gazzinelli G et al. (1997) Factors affecting high and low human IgE responses to schistosome worm antigens in an area of Brazil endemic for Schistosoma mansoni and hookworm. American Journal of Tropical Medicine and Hygiene 57, 487494.
  • World Health Organization (2002) Prevention and Control of Schistosomiasis and Soil-Transmitted Helminthiasis. WHO Technical Report Series 912, Geneva.
  • Yoshida A, Maruyama H, Yabu Y, Amano T, Kobayakawa T & Ohta N (1999) Immune response against protozoal and nematodal infection in mice with underlying Schistosoma mansoni infection. Parasitology International 48, 7379.