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Murine Models for Trypanosoma brucei gambiense Disease Progression—From Silent to Chronic Infections and Early Brain Tropism

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In vitro and in vivo growth characteristics of T. b. gambiense field isolates.

A. In vitro culture of Tbg1122, Tbg1166 and Tbg1135 isolates after adaptation to axenic culture conditions. Cultures were seeded with adapted trypanosomes (5.104/ml) in supplemented MEM medium and enumerated every 24 h. The mean trypanosome densities±standard error of the mean of 4 independent cultures is presented. Similar doubling times were obtained with the three isolates (15.9 h, 15.8 h and 14.6 h respectively). B–D. Parasitaemia levels in immunocompetent (BALB/c), immunodeficient (NOD/SCID and cyclophosphamide-treated BALB/c) mice infected with the different field isolates. Parasitaemia was measured from tail-blood either by direct observation of the wet films under the microscope or by using a haemacytometer. The limit of detection was estimated at about 104 parasites/ml. B. Represents the results of one representative BALB/c mouse (n = 6) infected i.p. with 106 of the Tbg945 blood isolate. All infected mice showed successive waves of parasitaemia and died within 6–8 months PI. C. Represents the mean parasitaemia in NOD/SCID mice infected with 103 Tbg1122c (n = 4), Tbg1166c (n = 6), Tbg1135c (n = 9) or Tbg1135b (n = 10) isolates. D. Represents the results of one representative BALB/c mouse infected with 1–5×106 Tbg1122b, Tbg1166b (n = 10) or Tbg1135b blood (n = 6) isolates with (+cyclo) or without (−cyclo) prior administration (24 h before infection) of cyclophosphamide (200 mg/kg). Solid symbols indicate culture isolates, open symbols indicate blood isolates of Tbg1166 (▴ , ▵), Tbg1122 (▪ , □) and Tbg1135 (• , ○).

Figure 1

doi: https://doi.org/10.1371/journal.pntd.0000509.g001