Elsevier

Acta Tropica

Volume 117, Issue 3, March 2011, Pages 189-195
Acta Tropica

Co-infection with Ascaris lumbricoides modulates protective immune responses against Giardia duodenalis in school Venezuelan rural children

https://doi.org/10.1016/j.actatropica.2010.12.001Get rights and content

Abstract

We evaluated the effect of Ascaris lumbricoides on Giardia duodenalis infection and TH1/TH2 type immune mechanisms toward this parasite in 251 rural parasitized and 70 urban non-parasitized school children. The children were classified according to light (0–5000 eggs/g faeces) or moderate (>5001–50,000 eggs/g faeces) A. lumbricoides infection. Anti G. duodenalis skin hyper-reactivity, IgE, IgG, IL-13, IFN γ, IL6 and IL-10 levels were compared among G. duodenalis infected and non-infected children according to light or moderate A. lumbricoides infection. It was found that 62% of the A. lumbricoides moderately infected children were co-infected by G. duodenalis compared to 45% of the lightly infected group. After treatment, 42% of the A. lumbricoides moderately group were infected with G. duodenalis compared to 11% of their lightly counterparts, being A. lumbricoides IL-10 levels higher (p < 0.0001) in the moderately infected group. In the A. lumbricoides lightly parasitized children, G. duodenalis infection was associated to a significant increase (p < 0.005) of the levels of G. duodenalis IL-13, IFN-γ, IL-6, IgE, IgG and skin test hyper reactivity. In contrast, there was no effect of G. duodenalis infection in the elevation of these parameters among the A. lumbricoides moderately parasitized group, being those levels similarly lower as those observed in the control group. Inverse correlations were found between the levels of anti G duodenalis antibodies, skin test hyper-reactivity and cytokines with the intensity of A. lumbricoides infection (p > 0.0001) and A. lumbricoides IL-10 levels (p > 0.0001), suggesting that co-infection with A. lumbricoides may affect both TH1 and TH2 type immunity against G. duodenalis that may play an important role in the susceptibility to the infection after chemotherapy in children from endemic areas.

Graphical abstract

Giardia duodenalis stimulates protective immune responses in rural children. However, co-infection of Ascaris lumbricoides may modulate these responses affecting the resistance against G. duodenalis in rural Venezuelan children.

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Research highlights

▶ We studied the effect of A. lumbricoides co- infection on the course of giardiasis. ▶ A group of 251 rural and 70 urban school children was evaluated. ▶ Moderate A. lumbricoides intensities correlated with a high prevalence of giardiasis. ▶ G. duodenalis stimulated TH2/TH1 immunity only in Ascaris lightly infected children. ▶ Moderate worm burdens decreased G. duodenalis immunity favoring recurrent infection.

Introduction

Giardia is a ubiquitous enteric protozoan that infects humans, domestic animals and wildlife worldwide. Due to its importance in world health, Giardia has been included in the WHO Neglected Diseases Initiative (Savioli et al., 2006). In Venezuela, 45% of rural and 26% of urban children may be infected with Giardia duodenalis (Devera et al., 1998, Simoes et al., 2000).

Studies performed in animal models have indicated that components of both innate and acquired immunity are stimulated during giardiasis although the participation of these mechanisms in the elimination of the parasite has been controversial. For example, it has been demonstrated that IL-6 deficient mice are unable to control the infection compared to their wild type counterparts (Bienz et al., 2003, Zhou et al., 2003). In addition, mast cells which are an important source of IL-6 in animal experiments are crucial for controlling acute mice infections (Li et al., 2004). Mast cell degranulation leads to increases in smooth muscle contractility promoting intestinal transit and parasite elimination in mice infected with Giardia (Li et al., 2007). In contrast, it has been also reported that a previous and acute co-infection with Trichinella spiralis that induces strong TH2 type intestinal inflammation including mast cell reactivity, promotes the growth of G. lamblia in mice (Von Allmen et al., 2006). On the other hand, there is evidence that T cell deficient mice also fail to eliminate Giardia infection (Heyworth et al., 1987) and that murine macrophages treated with recombinant IFN-γ and bacterial lipopolysaccharide (LPS) ingested a significantly higher number of in vitro-grown trophozoites than untreated macrophages, indicating a possible role of IFN-γ in the clearance of the parasite (Belosevic and Daniels, 1992). Furthermore, treatment of wild-type or B-cell-deficient mice with antibodies to CD4+ T cells prevents elimination of G. lamblia and Giardia muris (Singer and Nash, 2000). Nevertheless, this study showed that the production of IFN-γ or IL-4 is not required for the protection from G. lamblia. Other experiments have indicated that IgA-deficient mice as well as B-cell deficient mice are not able to eradicate late infections of either G. muris or G. lamblia, suggesting that both B cells and IgA are required for the control of chronic infections (Langford et al., 2002). More recent studies showed that cyst elimination from experimental infected gerbils is associated to the presence of secretory IgA but not to serum IgG1 or IgG2 antibodies (Amorim et al., 2010). Other studies have reported that oral administration of G. duodenalis excretory secretory antigens in Balb/c mice is followed by an increase in the production of total and specific serum IgE (Jiménez et al., 2004) accompanied by eosinophylic infiltration, hyper-cellularity and enterocytic desquamation in the small and large intestine of the mice. These results may suggest the participation of TH2 type responses in the immunity against Giardia (Jiménez et al., 2004).

It has been proposed that in humans, a fully developed immune system may resolve the acute phase of the infection spontaneously emphasizing the effectiveness of innate host defenses in the control of the infection (Eckmann, 2003). Also, it has been demonstrated that human infection with Giardia results in increased levels of anti-Giardia secretory and serum IgA antibodies (Faubert, 2000, Rodríguez et al., 2004, Jiménez et al., 2009) In addition, impaired IgA responses to Giardia heat shock antigen have been observed in Gambian children with persistent diarrhoea and giardiasis (Char et al., 1993). Moreover, Anti-Giardia secretory IgA detected in human breast milk can protect lactating children against giardiasis early in life (Tellez et al., 2003). However, the participation of other possible protective mechanisms such as TH1/TH2 type cytokines and IgE or IgG antibodies in human giardiasis has been poorly studied.

On the other hand, giardiasis in tropical environments rarely occurs alone and children from endemic areas are usually co-infected with intestinal nematodes (Pennycook et al., 2000). It has been reported that chronic helminth infections may negatively influence immunity against tuberculosis and other diseases of public health importance (Markus and Finchman, 2007). Also, intestinal helminthic infections can suppress immune responses toward non-relate antigens in tropical areas where these infections are endemic (Van Riet et al., 2007). The mechanisms by which these parasites modulate other immune responses are still not clear and may vary according to the intensity of the infection (Cooper, 2009). In this work we evaluated the possible influence of Ascaris lumbricoides co-infection on the development of TH1 and TH2 immune responses against G. duodenalis as well as on the susceptibility to giardiasis in a group of Venezuelan school children chronically exposed to both parasites.

Section snippets

Study population

We carried out a longitudinal study of the school population (6–12 years) of the Madre Nueva community, formed by a small group of rural farmers (235 families) working in cacao plantations located at the coastline of San Jose de Rio Chico (10.18N; 65.59W), Miranda State, Venezuela. The community lacked adequate sanitary conditions that resulted in a high prevalence of intestinal parasitic infections (Hagel et al., 2008). A control group of healthy non-parasitized children from a private urban

Socioeconomic and environmental factors

We evaluated a group of 251 sex-balanced school children (6–12 years) living in a rural farmer community. They all attended the same primary school and had received three meals per day at the school during the last 2 years before the evaluation. Therefore, they were well nourished and we did not find noticeable differences of the anthropometric parameters, when compared with the urban healthy control group (Table 1). All the rural children shared the same high risk from environmental factors

Discussion

Giardia is a worldwide parasitic infection that causes intestinal symptoms ranging from diarrhoea to constipation, nausea, headache and flatulence (Flanagan, 1992), affecting the quality of life of many children living at conditions of poverty which place them more susceptible to intestinal infections (Savioli et al., 2006). The understanding of the mechanisms involved in the immunity against G. duodenalis may contribute to the design of strategies to control or eliminate this parasitic

Acknowledgements

We appreciate the collaboration of Mrs. Lennys Urbina and Mrs. Loana Gutierrez for logistic and administrative support. We appreciate very much the collaboration of the laboratory from Rio Chico Hospital for the performance of stool examinations. We are grateful to Professor Maria Eugenia Pinardi for the revision of the manuscript. This work was financed by FONACIT: Project: G-2005000371 and CDCH: Project: 0966012006.

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