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(Eh) y metanólico (Em) de Pera distichophylla sobre un aislado de ...

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M. T. GALáN-PUCHADES and A. OSUNA<br />

in an increase of T. cruzi parasitaemia, precisely<br />

one of the risks favouring vertical transmission.<br />

Additionally, helminths can also contribute to a<br />

lower IFN-g production via a predominant Th-2<br />

response in pregnant women. Therefore, it would<br />

be interesting to evaluate the helminthological<br />

status of chagasic pregnant women and its possible<br />

influence on vertical transmission.<br />

10<br />

DISCUSSION<br />

In or<strong>de</strong>r to address the questions of whether<br />

helminth infection could affect the susceptibility to<br />

subsequent co-infection with T. cruzi, and whether<br />

a changing environment and cytokine profile<br />

induced by worms may influence the outcome of<br />

CD compared with hosts exclusively infected with<br />

T. cruzi, it was fo<strong>un</strong>d that the presence of helminths<br />

modifies both the susceptibility and, in most cases,<br />

the course of CD.<br />

Concerning susceptibility, in all the studied hosts<br />

(humans, mice, dogs and primates) the presence<br />

of worms increases the likelihood to acquire CD<br />

mainly in the helminth chronic phase. In addition,<br />

co-infection seems to lengthen survivorship of coinfected<br />

hosts compared with those only harboring<br />

T. cruzi. The presence of helminths also tends to<br />

increase T. cruzi parasitaemia and certain helminths<br />

may even improve the health status of chagasic<br />

hosts.<br />

One of the main implications of these findings<br />

is that helminth co-infections could potentially<br />

modify the course of CD among patients with the<br />

same T. cruzi DTU (discrete typing <strong>un</strong>its) (Monteiro<br />

et al., 2007).<br />

In the last two <strong>de</strong>ca<strong>de</strong>s, studies explaining<br />

severe forms of CD have mainly been based on<br />

imm<strong>un</strong>ological findings (Dutra et al., 2005, Rodrigues<br />

et al., 2010). Chagasic myocarditis is<br />

thought to be due to the presence of parasites in<br />

the lesions. However, an <strong>un</strong>balanced imm<strong>un</strong>e homeostasis<br />

can trigger parallel autoimm<strong>un</strong>e phenomena<br />

which increase the imm<strong>un</strong>e response,<br />

thus worsening the outcome of the disease (Gutierrez<br />

et al., 2009). Several results evi<strong>de</strong>nce that an<br />

exacerbated Th1-like specific imm<strong>un</strong>e response<br />

against T. cruzi with high levels of IFN-γ and low<br />

levels of the anti-inflamatory cytokine IL-10 is established<br />

in T. cruzi-infected individuals present-<br />

ing cardiac disease (Gomes et al., 2003). In addition,<br />

there is some limited evi<strong>de</strong>nce regarding the<br />

role of Th17-mediated responses to T. cruzi. The<br />

IL-17 produced during the acute phase of CD controls<br />

cardiac inflammation by modulating the Th1<br />

response, and this pro-inflammatory IL-17 is also<br />

required for the elimination of T. cruzi (Gue<strong>de</strong>s et<br />

al., 2010; Miyazaki et al., 2010). In contrast IL-<br />

27, which suppresses Th17 responses, is beneficial<br />

for the host during T. cruzi infection (Yoshida<br />

and Miyazaki, 2008).<br />

Surprisingly, there is no mention in the literature<br />

that evaluates the possible role of helminth<br />

infections in human CD when helminths are able<br />

to suppress all types (Th1, Th2, and Th17) of responses<br />

(see ref Osada and Kanazawa, 2010).<br />

Consi<strong>de</strong>ring the classical Th1/Th2 paradigm, it is<br />

reasonable to speculate that a helminth-induced<br />

Th2 response with production of IL-4, IL-5, IL-6<br />

and IL-10 skewing with downregulation of Th1<br />

imm<strong>un</strong>e responses could result in an amelioration<br />

of Th1 diseases, such as CD. As IL-4 is known to<br />

suppress Th17 <strong>de</strong>velopment (Romagnani, 2006), a<br />

Th17 response could also be suppressed as well as<br />

Th1 response in helminth-infected hosts. In fact,<br />

certain helminth infections reduce IL-17 mRNA<br />

by MLN cells and inhibit IL-17 production (Elliot<br />

et al., 2008). This is of relevance when consi<strong>de</strong>ring<br />

persistent parasites such as helminths which<br />

are wi<strong>de</strong>ly distributed in humans in <strong>de</strong>veloping<br />

co<strong>un</strong>tries (Maizels et al., 1993), where they coexist<br />

with T. cruzi. Wormy populations are exposed to<br />

two potential risks, namely an increased susceptibility<br />

to T. cruzi and a yet <strong>un</strong>researched course of<br />

the disease. All of this should prompt research on<br />

the possible epi<strong>de</strong>miological relevance of helminth<br />

infections and the impact when controlling them<br />

on the inci<strong>de</strong>nce or the pathogenesis of CD. The<br />

presence of helminth co-infections may represent<br />

a much more important challenge for public health<br />

than recognized <strong>un</strong>til now.<br />

In other co-infections of human parasites such<br />

as malaria and hookworms, it has been stated<br />

that it would be possible to <strong>de</strong>fine co-infection<br />

as a specific “disease”, separate from malaria by<br />

itself, or hookworm by itself (Payne et al., 2009),<br />

and this may also hold true for CD and helminths.<br />

Thus, gathering more reliable data on the true<br />

parasitological status of all chagasic patients would<br />

be <strong>de</strong>sirable.<br />

Rev. Ibero-Latinoam. Parasitol. (2012); 71 (1): 5-13

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