Jamonneau, V. | Search bioRxiv

bioRxiv2018

Ebola outbreak brings to light an unforeseen impact of tsetse control on sleeping sickness transmission in Guinea.

In addition to the thousands of deaths due the unprecedented ebola outbreak that stroke West Africa (2014-2016), national health systems in affected countries were deeply challenged impacting a number of diseases control programs. Here we describe the case of Human African Trypanosomiasis (HAT), a deadly neglected tropical disease due to a trypanosome transmitted by tsetse flies for which no vaccine nor chemoprophylaxis exists. Data are presented for the disease focus of Boffa in Guinea where a pilot elimination project combining medical screening and vector control was launched in 2012. During ebola, HAT active screening activities were postponed and passive surveillance also was progressively impaired. However, tsetse control using small insecticide impregnated targets could be maintained. The over two years disruption of screening activities led to a dramatic increase of HAT prevalence, from 0.7% in 2013 (21/2885) to 2% (69/3448) in 2016, reaching epidemic levels (>5%) in some villages. In deep contrast, control levels reached in 2013 (0.1%; 7/6564) were maintained in areas covered with impregnated targets as no cases were found in 2016 (0/799). In Boffa, ebola has thus incidentally provided a unique framework to assess the impact of current HAT control strategies. A first lesson is that the \"screen and treat\" strategy is fragile as rapid bursts of the disease may occur in case of disruption. A second lesson is that vector control reducing human-tsetse contacts, even implemented alone, is effective in providing a good level of protection against infection. This advocates for a greater attention being paid to the combination of tsetse control together with medical activities in aiming to reach the HAT elimination objective in Africa.

epidemiology↗

bioRxiv2017

T cell activation and the HLA locus associate with latent infections of human African trypanosomiasis

Infections by many pathogens can result in a wide range of phenotypes, from severe to mild, or even asymptomatic. Understanding the genetic basis of these phenotypes can lead to better tools to treat patients or detect reservoirs. To identify human genetic factors that contribute to symptoms diversity, we examined the range of disease severities caused by the parasite T. b. gambiense, the primary cause of human African trypanosomiasis (HAT). We analyzed the transcriptomes of immune cells from both symptomatic HAT cases and individuals with latent infections. Our analysis identified several genes and pathways that associated with the latent phenotype, primarily suggesting increased T and B cell activation in HAT patients relative to latent infections. We also used these transcriptome data to conduct an exome-wide single nucleotide polymorphism (SNP) association study. This suggested that SNPs in the human major histocompatibility locus (HLA) associate with severity, supporting the transcription data and suggesting that T cell activation is a determining factor in outcome. Finally, to establish if T cell activation controls disease severity, we blocked co-stimulatory dependent T cell activation in an animal model for HAT. This showed that reducing T cell activation during trypanosome infection improves symptoms and reduces parasitemia. Our data has used a combination of transcriptome-wide analysis and an in vivo model to reveal that T cell activation and the HLA locus associate with the development of symptoms during HAT. This may open new avenues for the development of new therapeutics and prognostics.

genetics↗