Trypanosoma brucei gambiense Infections in Mice Lead to Tropism to the Reproductive Organs, and Horizontal and Vertical Transmission

Abstract

Trypanosoma brucei gambiense, transmitted by the tsetse fly, is the main causative agent of Human African trypanosomosis in West Africa and poses a significant health risk to 70 million people. Disease progression varies depending on host immunity, but usually begins with a haemo-lymphatic phase, followed by parasite invasion of the central nervous system.In the current study, the tropism of T. b. gambiense 1135, causing a low level chronic ‘silent’ infection, was monitored in a murine model using bioluminescence imaging and PCR. A tropism to the reproductive organs, in addition to the central nervous system, after 12–18 months of infection was observed. Bioluminescent analysis of healthy females crossed with infected males showed that 50%, 62.5% and 37.5% of the female mice were subsequently positive for parasites in their ovaries, uteri and brain respectively. Although PCR confirmed the presence of parasites in the uterus of one of these mice, the blood of all mice was negative by PCR and LAMP. Subsequently, bioluminescent imaging of the offspring of infected female mice crossed with healthy males indicated parasites were present in the reproductive organs of both male (80%) and female (60%) offspring.These findings imply that transmission of T. b. gambiense 1135 occurs horizontally, most probably via sexual contact, and vertically in a murine model, which raises the possibility of a similar transmission in humans. This has wide reaching implications. Firstly, the observations made in this study are likely to be valid for wild animals acting as a reservoir for T. b. gambiense. Also, the reproductive organs may act as a refuge for parasites during drug treatment in a similar manner to the central nervous system. This could leave patients at risk of a relapse, ultimately allowing them to act as a reservoir for subsequent transmission by tsetse and possibly, horizontally and vertically.

Do Cryptic Reservoirs Threaten Gambiense-Sleeping Sickness Elimination?

“…This observation is in line with the fact that trypanosomes can survive in the extravascular spaces of diverse organs such as the heart, the central nervous system, and the skin 15 , 16 , 17 . Experimental infections in animals confirmed that parasites may be undetectable in the blood but hidden in different organs and tissues 18 , 19 , 20 , 21 , including the skin, from where they can be ingested by tsetse flies 22 , 23 . It was only recently that researchers began to investigate the underlying host–parasite interaction mechanisms responsible for those latent infections.…”

The animal trypanosomiases and their chemotherapy: a review

“…Instead, this parasite is transmitted among horses and other equids during mating (Claes et al 2005). Of note, vertical or perinatal transmission of trypanosomes other than T. b. equiperdum in the reproductive tissues has been reported (Griffin, 1983; Melendez et al 1993; Lindner and Priotto, 2010; Biteau et al 2016), although the role and relative importance of this mode of transmission in the field is not clear.…”

Salivarian Trypanosomosis: A Review of Parasites Involved, Their Global Distribution and Their Interaction With the Innate and Adaptive Mammalian Host Immune System

“…One striking example is T. equiperdum, which is hardly studied in comparison to other infections due to the fact that it causes a disease characterized by sexual transmission in horses, a feature so far not reported in mice. In fact, only a single report is available on experimental sexual transmission of trypanosomosis in mice, and this report is dealing with T. b. gambiense ( 86 ). However, whether sexual transmission of T. brucei gambiense is a real issue in human trypanosomosis, remains a matter of debate ( 87 ) and more species-specific research is needed to resolve these issues.…”