Mathurin Koffi

Population genetics of Trypanosoma brucei gambiense, the agent of sleeping sickness in Western Africa

Human African trypanosomiasis, or sleeping sickness caused by Trypanosoma brucei gambiense, occurs in Western and Central Africa. T. brucei s.l. displays a huge diversity of adaptations and host specificities, and questions about its reproductive mode, dispersal abilities, and effective size remain under debate. We have investigated genetic variation at 8 microsatellite loci of T. b. gambiense strains isolated from human African trypanosomiasis patients in the Ivory Coast and Guinea, with the aim of knowing how genetic information was partitioned within and between individuals in both temporal and spatial scales. The results indicate that (i) migration of T. b. gambiense group 1 strains does not occur at the scale of West Africa, and that even at a finer scale (e.g., within Guinea) migration is restricted; (ii) effective population sizes of trypanosomes, as reflected by infected hosts, are probably higher than what the epidemiological surveys suggest; and (iii) T. b. gambiense group 1 is most likely a strictly clonally reproducing organism.

Untreated Human Infections by Trypanosoma brucei gambiense Are Not 100% Fatal

The final outcome of infection by Trypanosoma brucei gambiense, the main agent of sleeping sickness, has always been considered as invariably fatal. While scarce and old reports have mentioned cases of self-cure in untreated patients, these studies suffered from the lack of accurate diagnostic tools available at that time. Here, using the most specific and sensitive tools available to date, we report on a long-term follow-up (15 years) of a cohort of 50 human African trypanosomiasis (HAT) patients from the Ivory Coast among whom 11 refused treatment after their initial diagnosis. In 10 out of 11 subjects who continued to refuse treatment despite repeated visits, parasite clearance was observed using both microscopy and polymerase chain reaction (PCR). Most of these subjects (7/10) also displayed decreasing serological responses, becoming progressively negative to trypanosome variable antigens (LiTat 1.3, 1.5 and 1.6). Hence, in addition to the “classic” lethal outcome of HAT, we show that alternative natural progressions of HAT may occur: progression to an apparently aparasitaemic and asymptomatic infection associated with strong long-lasting serological responses and progression to an apparently spontaneous resolution of infection (with negative results in parasitological tests and PCR) associated with a progressive drop in antibody titres as observed in treated cases. While this study does not precisely estimate the frequency of the alternative courses for this infection, it is noteworthy that in the field national control programs encounter a significant proportion of subjects displaying positive serologic test results but negative results in parasitological testing. These findings demonstrate that a number of these subjects display such infection courses. From our point of view, recognising that trypanotolerance exists in humans, as is now widely accepted for animals, is a major step forward for future research in the field of HAT.

Molecular analysis of archived blood slides reveals an atypical human Trypanosoma infection.

In 2003, a 10-month-old Ghanaian boy recovered from a Trypanosoma brucei infection, although the patient was not treated with antitrypanosomal drugs. Only T. brucei gambiense and T. brucei rhodesiense are able to infect humans, causing human African trypanosomiasis. The disease is considered 100% fatal if left untreated. The identity of the trypanosome was determined by DNA extraction from the archived stained blood slides followed by sequential application of polymerase chain reactions (PCRs) that are specific for the order, subgenus, species and subspecies, followed by genotyping with microsatellite PCR. Molecular analysis indicated that the parasites observed in the patients blood in 2003 belong to the T. brucei subspecies brucei, which is normally not infectious to humans. Next to the clinical message, this article provides technical information to extract successfully DNA from archived blood slides for subsequent molecular analysis and to identify a trypanosome by taxon-specific PCRs and microsatellite genotyping.

Population genomics reveals the origin and asexual evolution of human infective trypanosomes

Evolutionary theory predicts that the lack of recombination and chromosomal re-assortment in strictly asexual organisms results in homologous chromosomes irreversibly accumulating mutations and thus evolving independently of each other, a phenomenon termed the Meselson effect. We apply a population genomics approach to examine this effect in an important human pathogen, Trypanosoma brucei gambiense. We determine that T.b. gambiense is evolving strictly asexually and is derived from a single progenitor, which emerged within the last 10,000 years. We demonstrate the Meselson effect for the first time at the genome-wide level in any organism and show large regions of loss of heterozygosity, which we hypothesise to be a short-term compensatory mechanism for counteracting deleterious mutations. Our study sheds new light on the genomic and evolutionary consequences of strict asexuality, which this pathogen uses as it exploits a new biological niche, the human population. DOI: http://dx.doi.org/10.7554/eLife.11473.001

Accuracy of Individual Rapid Tests for Serodiagnosis of Gambiense Sleeping Sickness in West Africa

Background Individual rapid tests for serodiagnosis (RDT) of human African trypanosomiasis (HAT) are particularly suited for passive screening and surveillance. However, so far, no large scale evaluation of RDTs has been performed for diagnosis of Trypanosoma brucei gambiense HAT in West Africa. The objective of this study was to assess the diagnostic accuracy of 2 commercial HAT-RDTs on stored plasma samples from West Africa. Methodology/Principal findings SD Bioline HAT and HAT Sero-K-Set were performed on 722 plasma samples originating from Guinea and Côte d’Ivoire, including 231 parasitologically confirmed HAT patients, 257 healthy controls, and 234 unconfirmed individuals whose blood tested antibody positive in the card agglutination test but negative by parasitological tests. Immune trypanolysis was performed as a reference test for trypanosome specific antibody presence. Sensitivities in HAT patients were respectively 99.6% for SD Bioline HAT, and 99.1% for HAT Sero-K-Set, specificities in healthy controls were respectively 87.9% and 88.3%. Considering combined positivity in both RDTs, increased the specificity significantly (p≤0.0003) to 93.4%, while 98.7% sensitivity was maintained. Specificities in controls were 98.7–99.6% for the combination of one or two RDTs with trypanolysis, maintaining a sensitivity of at least 98.1%. Conclusions/Significance The observed specificity of the single RDTs was relatively low. Serial application of SD Bioline HAT and HAT Sero-K-Set might offer superior specificity compared to a single RDT, maintaining high sensitivity. The combination of one or two RDTs with trypanolysis seems promising for HAT surveillance.

Comparison of cytokine plasma levels in human African trypanosomiasis

Background  Immunological studies suggest that human African trypanosomiasis (HAT) is associated with inflammatory responses. A better understanding of the complex cytokine interactions regulating HAT infections is essential to elucidate the mechanisms of generalized immunosuppression.

Population Genetics and Reproductive Strategies of African Trypanosomes: Revisiting Available Published Data

Trypanosomatidae are a dangerous family of Euglenobionta parasites that threaten the health and economy of millions of people around the world. More precisely describing the population biology and reproductive mode of such pests is not only a matter of pure science, but can also be useful for understanding parasite adaptation, as well as how parasitism, specialization (parasite specificity), and complex life cycles evolve over time. Studying this parasite’s reproductive strategies and population structure can also contribute key information to the understanding of the epidemiology of associated diseases; it can also provide clues for elaborating control programs and predicting the probability of success for control campaigns (such as vaccines and drug therapies), along with emergence or re-emergence risks. Population genetics tools, if appropriately used, can provide precise and useful information in these investigations. In this paper, we revisit recent data collected during population genetics surveys of different Trypanosoma species in sub-Saharan Africa. Reproductive modes and population structure depend not only on the taxon but also on the geographical location and data quality (absence or presence of DNA amplification failures). We conclude on issues regarding future directions of research, in particular vis-à-vis genotyping and sampling strategies, which are still relevant yet, too often, neglected issues.

Do Cryptic Reservoirs Threaten Gambiense-Sleeping Sickness Elimination?

Trypanosoma brucei gambiense causes human African trypanosomiasis (HAT). Between 1990 and 2015, almost 440 000 cases were reported. Large-scale screening of populations at risk, drug donations, and efforts by national and international stakeholders have brought the epidemic under control with <2200 cases in 2016. The World Health Organization (WHO) has set the goals of gambiense-HAT elimination as a public health problem for 2020, and of interruption of transmission to humans for 2030. Latent human infections and possible animal reservoirs may challenge these goals. It remains largely unknown whether, and to what extend, they have an impact on gambiense-HAT transmission. We argue that a better understanding of the contribution of human and putative animal reservoirs to gambiense-HAT epidemiology is mandatory to inform elimination strategies.

A targeted door-to-door strategy for sleeping sickness detection in low-prevalence settings in Côte d’Ivoire

Significant efforts to control human African trypanosomiasis (HAT) over the three past decades have resulted in drastic reductions of disease prevalence in Côte d’Ivoire. In this context, the costly and labor-intensive active mass screening strategy is no longer efficient. In addition to a more cost-effective passive surveillance system being implemented in this low-prevalence context, our aim was to develop an alternative targeted active screening strategy. In 2012, we carried out a targeted door-to-door (TDD) survey focused on the immediate vicinities of former HAT patients detected in the HAT focus of Bonon and compared the results to those obtained during classical active mass screening (AMS) surveys conducted from 2000 to 2012 in the same area. The TDD that provides a friendlier environment, inviting inhabitants to participate and gain awareness of the disease, detected significantly more HAT cases than the AMS. These results suggest that the TDD is an efficient and useful strategy in low-prevalence settings where very localized transmission cycles may persist and, in combination with passive surveillance, could help in eliminating HAT.

Introducing the TrypanoGEN biobank: A valuable resource for the elimination of human African trypanosomiasis

Hamidou Ilboudo, Harry Noyes, Julius Mulindwa, Magambo Phillip Kimuda, Mathurin Koffi, Justin Windingoudi Kaboré, Bernadin Ahouty, Dieudonné Mumba Ngoyi, Olivier Fataki, Gustave Simo, Elvis Ofon, John Enyaru, John Chisi, Kelita Kamoto, Martin Simuunza, Vincent P. Alibu, Veerle Lejon, Vincent Jamonneau, Annette Macleod, Mamadou Camara, Bruno Bucheton, Christiane Hertz-Fowler, Issa Sidibe, Enock Matovu*, for the TrypanoGEN Research Group as members of The H3Africa Consortium