The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes

Abstract

The role of mammalian skin in harbouring and transmitting arthropod-borne protozoan parasites has been overlooked for decades as these pathogens have been regarded primarily as blood-dwelling organisms. Intriguingly, infections with low or undetected blood parasites are common, particularly in the case of Human African Trypanosomiasis caused by Trypanosoma brucei gambiense. We hypothesise, therefore, the skin represents an anatomic reservoir of infection. Here we definitively show that substantial quantities of trypanosomes exist within the skin following experimental infection, which can be transmitted to the tsetse vector, even in the absence of detectable parasitaemia. Importantly, we demonstrate the presence of extravascular parasites in human skin biopsies from undiagnosed individuals. The identification of this novel reservoir requires a re-evaluation of current diagnostic methods and control policies. More broadly, our results indicate that transmission is a key evolutionary force driving parasite extravasation that could further result in tissue invasion-dependent pathology.DOI: http://dx.doi.org/10.7554/eLife.17716.001

Adipose Tissue: A Safe Haven for Parasites?

“…When parasites penetrate the brain, they cause neuropsychiatric and sleep abnormalities [16–20]. Tropism has recently been described to the skin and testis, which is important for transmission by the tsetse and sexually, respectively [17–19,21]. T. brucei parasites were also found in the skin of 0.5% patients screened for Onchocerca microfilaria at the Democratic Republic of Congo, suggesting that undiagnosed individuals may be a previously unknown source of transmission [17].…”

“…recently showed by quantitative PCR that the AT harbors around 10-fold more parasites than the average number found in the blood in chronic stages of the disease [20]. Interestingly, in the two studies describing tropism for the skin, many parasites were found in the vicinity of subcutaneous adipocytes [17,18]. Although it remains to be compared the relative number of parasites in skin, visceral adipose tissue and testis from the same mouse, there is no doubt that the adipose tissue is one of the major parasite reservoirs.…”

“…Replicating parasites have been found both in the AT and in the skin, suggesting these tissue environments provide enough nutrients to support parasite growth [17,18,20]. A large number of non-dividing transmissible forms have also been found in the two tissues [15], suggesting that transmission can happen from extra-vascular sites [17,20]. …”

“…T. brucei displays waveforms that seem best adapted to move in confined viscous environments such as [17,20] tissue spaces [24]. Live imaging revealed that indeed some T. brucei slender parasites present a fast persistent movement, while others are less mobile [17].…”

Evolving anti-disease strategies from biochemical pathogenesis of african trypanosomiasis

“…Trypanosomes in infected hosts migrate to privileged extravascular sites which may be adipose tissues, dermis and subcutis of the skin, where they localize and serve as sources for subsequent recrudescence of active patent infection. [100][101][102] Therapeutic agents need to be capable of reaching tissues with sequestered parasites which are shielded from drug effects and in the event of failure to do so, the infected hosts has to recruit endogenous anti-disease strategies to control the infection or be supported exogenously with anti-disease interventions. Even in untreated cases, an argument is tenable for strategies investing in disease mitigation of the infected hosts.…”