Unraveling Chagas disease transmission through the oral route: Gateways to Trypanosoma cruzi infection and target tissues

Abstract

Oral transmission of Trypanosoma cruzi, the causative agent of Chagas disease, is the most important route of infection in Brazilian Amazon and Venezuela. Other South American countries have also reported outbreaks associated with food consumption. A recent study showed the importance of parasite contact with oral cavity to induce a highly severe acute disease in mice. However, it remains uncertain the primary site of parasite entry and multiplication due to an oral infection. Here, we evaluated the presence of T. cruzi Dm28c luciferase (Dm28c-luc) parasites in orally infected mice, by bioluminescence and quantitative real-time PCR. In vivo bioluminescent images indicated the nasomaxillary region as the site of parasite invasion in the host, becoming consistently infected throughout the acute phase. At later moments, 7 and 21 days post-infection (dpi), luminescent signal is denser in the thorax, abdomen and genital region, because of parasite dissemination in different tissues. Ex vivo analysis demonstrated that the nasomaxillary region, heart, mandibular lymph nodes, liver, spleen, brain, epididymal fat associated to male sex organs, salivary glands, cheek muscle, mesenteric fat and lymph nodes, stomach, esophagus, small and large intestine are target tissues at latter moments of infection. In the same line, amastigote nests of Dm28c GFP T. cruzi were detected in the nasal cavity of 6 dpi mice. Parasite quantification by real-time qPCR at 7 and 21 dpi showed predominant T. cruzi detection and expansion in mouse nasal cavity. Moreover, T. cruzi DNA was also observed in the mandibular lymph nodes, pituitary gland, heart, liver, small intestine and spleen at 7 dpi, and further, disseminated to other tissues, such as the brain, stomach, esophagus and large intestine at 21 dpi. Our results clearly demonstrated that oral cavity and adjacent compartments is the main target region in oral T. cruzi infection leading to parasite multiplication at the nasal cavity.

WHF IASC Roadmap on Chagas Disease

“…Oral transmission: Oral transmission is now more frequently recognized, especially in the Amazon region and the subtropical Andes (Venezuela, Colombia and Ecuador) [17]. It is now the primary mechanism of acute cases in the Brazilian Amazon and Venezuela [18,19], and is characterized by higher mortality during the acute phase than the vector-mediated acute disease [20]. Underreporting: Most estimates of the burden of CD are based on official mortality figures.…”

Evolutionary ecology of Chagas disease; what do we know and what do we need?

“…The transmission and the epidemiology of T. cruzi are influenced by the long‐term dynamics of host infection that is associated with the very peculiar life history of this protozoan parasite. Although oral transmission has been reported in humans and nonhuman hosts (Henriques, Henriques‐Pons, Meuser‐Batista, Ribeiro, & de Souza, ; de Noya & González, ; Sánchez & Ramírez, ; Silva‐dos‐Santos et al., ), typical infection starts with an acute phase where the parasite enters the host through microlesions of the skin before multiplying in the bloodstream and spreading to other tissues. In humans, this infective stage lasts for 4–8 weeks and it is usually asymptomatic, although it might present as a febrile illness with local reaction at the site of infection (Rassi et al., ).…”

Noninvasive Biological Samples to Detect and Diagnose Infections due to Trypanosomatidae Parasites: A Systematic Review and Meta-Analysis

“…Chagas Disease. Because T. cruzi, originally named Schyzotrypanum cruzi, possesses the capacity to cross the epithelium and to infect via the oral route [29,327,329], the presence of this pathogen in the milk has been searched for. T. cruzi was found in the milk of experimentally infected mice [328,330,331], and several reports describe the presence of this pathogen in the milk from pregnant women [332][333][334][335], as reviewed by Norman and Lopez-Vélez [336].…”