Monitoring the pleomorphism of Trypanosoma brucei gambiense isolates in mouse: Impact on its transmissibility to Glossina palpalis gambiensis
Introduction
Human African trypanosomiasis (HAT) is caused by trypanosomes belonging to Trypanosoma brucei species, transmitted to humans by tsetse flies. Trypanosoma brucei gambiense (T. b. gambiense) is responsible for the chronic form of HAT in West and Central Africa where the main vectors are Glossina species of the palpalis group (Hoare, 1972). The ability to transmit T. b. gambiense requires the completion of a complex life cycle by the parasite in the tsetse fly: establishment of the procyclic forms of the parasite in the midgut (immature infections) followed by the maturation of the parasites into metacyclic forms in the salivary gland (mature infections) (Vickerman, 1985, Welburn and Maudlin, 1999). The epidemiology of HAT is therefore determined to a large extent by the number of tsetse flies with mature infections in a specific area.
Previous study of the cyclical transmission of T. b. gambiense in Glossina palpalis gambiensis (G. p. gambiensis), showed substantial differences between different field isolates originated from the same sleeping sickness focus (Ravel et al., 2006). Whereas some isolates displayed only immature infections, one isolate gave both immature and mature infections and one led only to mature infections. Because such differences could have important implications for the epidemiology of the transmission of HAT, it is essential to determine the reasons for these differences. The trypanosome stock can play a role (Maudlin and Welburn, 1994) as can numerous factors such as the pleomorphism of the parasites. In the mammalian bloodstream, the parasite population is described as pleomorphic with slender and stumpy forms as well as transitional forms between the slender and stumpy forms defined as intermediate forms (Vickerman, 1965, Matthews et al., 2004). Trypanosomes first divide as long-slender bloodstream forms. At a certain threshold density, the trypanosomes differentiate to cell cycle-arrested short stumpy blood forms (Reuner et al., 1997, Vassella et al., 1997). This differentiation and the distinct biology of the slender and stumpy forms enable the trypanosome to fulfil its dual objectives in the mammalian host: to proliferate and to ensure transmission to tsetse fly (Matthews, 1999). The slender form parasites are adapted to exploiting the rich glucose environment of the blood (Bakker et al., 1995) and they undergo rapid multiplication, allowing them to establish the parasitaemia in the mammalian host. In contrast, the stumpy forms do not divide and there are changes in their enzyme and mitochondrial functions (Tyler et al., 1997) as they prepare for survival in the glucose-poor, poorly oxygenated environment of the tsetse gut. Stumpy forms thus appeared to be vector-transmissible (Seed and Wenck, 2003).
The aim of the present study was first to monitor the pleomorphism of different isolates of T. b. gambiense during their development in mice and then to study the impact of this pleomorphism on the parasite transmissibility to G. p. gambiensis.
Section snippets
Trypanosomes
The three T. b. gambiense isolates used here (S1/1/6, S7/2/2 and S12/9/5) were isolated in 2002 by rodent inoculation from three HAT patients detected in the sleeping sickness focus of Bonon, Côte d’Ivoire. They all belong to T. b. gambiense group 1. One cryostabilate of each isolate, resulting from five previous passages in mice, was reactivated in two BALB/c mice. Then one more passage for multiplication was done before inoculation of six mice. Finally, each isolate was passaged only seven
Monitoring the parasitaemia and the pleomorphism of the three T. b. gambiense isolates
Each batch of six mice injected with the same isolate showed quite similar development of trypanosomes (Fig. 2). To compare the three isolates, the median parasitaemia was calculated for each isolate and is shown in Fig. 3. The gaps in the lines result from the parasitaemia not being determined on exactly the same days for all three isolates.
S1/1/6 displayed a first parasitaemia peak on day 5, followed by a short falling phase, then reached a parasitaemia plateau on day 16 with fluctuations
Discussion
The three T. b. gambiense isolates used here induced different infection patterns in mouse. While S1.1.6 and S12.9.5 maintained a parasitaemia plateau until the mice died, S7.2.2 rapidly showed disappearance of the parasites followed by a second parasitaemia plateau. A recent work from Holzmuller et al. (2008) also indicated different infection patterns in mouse for S7/2/2 and S1/1/6. On the other hand, this report did not mention the falling phase we observed for S7.2.2. Differences in the
Acknowledgement
We wish to thank Dr. Paul Chuchana for helpful comments on the manuscript.
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