Comparison of the infectivity of Trypanosoma cruzi insect-derived metacyclic trypomastigotes after mucosal and cutaneous contaminative challenges

Eickhoff, Christopher S.; Dunn, Brian Anthony; Sullivan, Nicole; Hoft, Daniel F.

doi:10.1590/s0074-02762013000400018

Cited by 14 publications

(16 citation statements)

References 11 publications

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“…route developed a higher brain parasitism and lower parasitemia than animals infected via the s.c. route, suggesting a preferential homing of the parasite to the brain after intranasal administration [ 34 ]. Interestingly, when mice are infected with the same strain simulating natural infection, by oral (oropharynx) or cutaneous (over a puncture wound) challenge, insect-derived trypomastigotes are more infective through oral inoculation [ 19 ]. Regardless of DTU (TcI or TcII strains), infection through gavage (intragastrically) presents less infectivity, parasitemia and mortality than intraperitoneal injection [ 35 ], as we have also observed with the Tulahuén strain (TcVI).…”

Section: Discussionmentioning

confidence: 99%

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Trypanosoma cruzi Infection through the Oral Route Promotes a Severe Infection in Mice: New Disease Form from an Old Infection?

et al. 2015

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Oral transmission of Chagas disease has been documented in Latin American countries. Nevertheless, significant studies on the pathophysiology of this form of infection are largely lacking. The few studies investigating oral route infection disregard that inoculation in the oral cavity (Oral infection, OI) or by gavage (Gastrointestinal infection, GI) represent different infection routes, yet both show clear-cut parasitemia and heart parasitism during the acute infection. Herein, BALB/c mice were subjected to acute OI or GI infection using 5x104 culture-derived Trypanosoma cruzi trypomastigotes. OI mice displayed higher parasitemia and mortality rates than their GI counterparts. Heart histopathology showed larger areas of infiltration in the GI mice, whereas liver lesions were more severe in the OI animals, accompanied by higher Alanine Transaminase and Aspartate Transaminase serum contents. A differential cytokine pattern was also observed because OI mice presented higher pro-inflammatory cytokine (IFN-γ, TNF) serum levels than GI animals. Real-time PCR confirmed a higher TNF, IFN-γ, as well as IL-10 expression in the cardiac tissue from the OI group compared with GI. Conversely, TGF-β and IL-17 serum levels were greater in the GI animals. Immunolabeling revealed macrophages as the main tissue source of TNF in infected mice. The high mortality rate observed in the OI mice paralleled the TNF serum rise, with its inhibition by an anti-TNF treatment. Moreover, differences in susceptibility between GI versus OI mice were more clearly related to the host response than to the effect of gastric pH on parasites, since infection in magnesium hydroxide-treated mice showed similar results. Overall, the present study provides conclusive evidence that the initial site of parasite entrance critically affects host immune response and disease outcome. In light of the occurrence of oral Chagas disease outbreaks, our results raise important implications in terms of the current view of the natural disease course and host-parasite relationship.

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Section: Discussionmentioning

confidence: 99%

“…Despite this, there are controversies about mortality rates, because oral transmission gained more attention after outbreaks over the years. Previous studies suggested that metacyclic trypomastigotes are more infective by oral than cutaneous challenge, emphasizing the higher severity of oral infection [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Trypanosoma cruzi Infection through the Oral Route Promotes a Severe Infection in Mice: New Disease Form from an Old Infection?

et al. 2015

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“…Previous studies have shown that pathogenicity in mice and dogs is relative to the quantity or parasite inoculated and to the route of inoculation [43][44][45]. Specifically, metacyclic trypomastigotes have been shown to be more efficient by oral than cutaneous routes in mice [46]. In humans, oral infection with T. cruzi is associated with a high mortality rate (8-35% compared to < 5-10% when transmitted by the vector) [47] and an attack rate of up to 100% [48].…”

Section: Discussionmentioning

confidence: 99%

Selected cardiac abnormalities in Trypanosoma cruzi serologically positive, discordant, and negative working dogs along the Texas-Mexico border

et al. 2020

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Background: Chagas disease is increasingly recognized in the southern U.S., where triatomine vectors transmit Trypanosoma cruzi among wildlife and domestic dogs with occasional vector spillover to humans. As in humans, clinical outcome in dogs is variable, ranging from acute death to asymptomatic infections or chronic heart disease. In order to characterize cardiac manifestations of T. cruzi infections, we tracked a cohort of naturally-infected dogs and a matched cohort of uninfected dogs. We hypothesized that selected measures of cardiac disease (abnormal rate, abnormal rhythm, and elevated cardiac troponin I (cTnI; a biomarker of cardiac injury)) would occur more commonly in infected than uninfected dogs matched by age, breed, sex and location. In addition to the clearly positive and negative dogs, we specifically tracked dogs with discordant test results across three independent serological assays to gather clinical data that might elucidate the infection status of these animals and inform the utility of the different testing approaches. Results: We placed an ambulatory ECG monitor (Holter) on 48 government working dogs and analyzed 39 successful recordings that met length and quality criteria from 17 T. cruzi-infected, 18 uninfected dogs and 4 dogs with discordant results. Overall, 76.5% of positive, 100.0% of discordant, and 11.1% of negative dogs showed > 1 ECG abnormality (p < 0.0001), and positive and discordant dogs had a higher mean number of different types of ECG abnormalities than negative dogs (p < 0.001-0.014). The most common cardiac abnormalities included supraventricular and ventricular arrhythmias and atrioventricular block. Positive dogs had higher serum concentrations of cTnI than both negative dogs (p = 0.044) and discordant dogs (p = 0.06). Based on dog handler reports, nearly all (4/5; 80%) dogs with reported performance decline or fatigue were T. cruzi-infected dogs.Conclusions: Further understanding cardiac manifestations in dogs naturally infected with T. cruzi is critical for prognostication, establishing a baseline for drug and vaccine studies, and better understanding of zoonotic risk.

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“…We, therefore, designed an additional experiment to evaluate transcutaneous transmission through contaminated bed bug feces using a protocol described previously 10. Briefly, we shaved portions of the backs of 10 2-month-old uninfected mice using an electric razor.…”

Section: Methodsmentioning

confidence: 99%

Bed Bugs (Cimex lectularius) as Vectors of Trypanosoma cruzi

Salazar¹,

Castillo-Neyra²,

Tustin³

et al. 2015

The American Journal of Tropical Medicine and Hygiene

138

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Populations of the common bed bug, Cimex lectularius, have recently undergone explosive growth. Bed bugs share many important traits with triatomine insects, but it remains unclear whether these similarities include the ability to transmit Trypanosoma cruzi, the etiologic agent of Chagas disease. Here, we show efficient and bidirectional transmission of T. cruzi between hosts and bed bugs in a laboratory environment. Most bed bugs that fed on experimentally infected mice acquired the parasite. A majority of previously uninfected mice became infected after a period of cohabitation with exposed bed bugs. T. cruzi was also transmitted to mice after the feces of infected bed bugs were applied directly to broken host skin. Quantitative bed bug defecation measures were similar to those of important triatomine vectors. Our findings suggest that the common bed bug may be a competent vector of T. cruzi and could pose a risk for vector-borne transmission of Chagas disease.

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Comparison of the infectivity of Trypanosoma cruzi insect-derived metacyclic trypomastigotes after mucosal and cutaneous contaminative challenges

Cited by 14 publications

References 11 publications

Trypanosoma cruzi Infection through the Oral Route Promotes a Severe Infection in Mice: New Disease Form from an Old Infection?

Trypanosoma cruzi Infection through the Oral Route Promotes a Severe Infection in Mice: New Disease Form from an Old Infection?

Selected cardiac abnormalities in Trypanosoma cruzi serologically positive, discordant, and negative working dogs along the Texas-Mexico border

Bed Bugs (Cimex lectularius) as Vectors of Trypanosoma cruzi

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