Differential virulence of Trypanosoma brucei rhodesiense isolates does not influence the outcome of treatment with anti-trypanosomal drugs in the mouse model.

Kariuki Ndung’U,Purity Kaari Gitonga,John Kibuthu Thuita,Raymond Ellie Mdachi,Richard Kiptum Kurgat,Geoffrey Njuguna Ngae,Grace Adira Murilla,Daniel Kahiga Thungu,Judith Kusimba Chemuliti,Joanna Eseri Auma,Martin Chtolongo Simuunza

doi:10.1371/journal.pone.0229060

Abstract

We assessed the virulence and anti-trypanosomal drug sensitivity patterns of Trypanosoma brucei rhodesiense (Tbr) isolates in the Kenya Agricultural and Livestock Research Organization-Biotechnology Research Institute (KALRO-BioRI) cryobank. Specifically, the study focused on Tbr clones originally isolated from the western Kenya/eastern Uganda focus of human African Trypanosomiasis (HAT). Twelve (12) Tbr clones were assessed for virulence using groups(n = 10) of Swiss White Mice monitored for 60 days post infection (dpi). Based on survival time, four classes of virulence were identified: (a) very-acute: 0-15, (b) acute: 16-30, (c) sub-acute: 31-45 and (d) chronic: 46-60 dpi. Other virulence biomarkers identified included: pre-patent period (pp), parasitaemia progression, packed cell volume (PCV) and body weight changes. The test Tbr clones together with KALRO-BioRi reference drug-resistant and drug sensitive isolates were then tested for sensitivity to melarsoprol (mel B), pentamidine, diminazene aceturate and suramin, using mice groups (n = 5) treated with single doses of each drug at 24 hours post infection. Our results showed that the clones were distributed among four classes of virulence as follows: 3/12 (very-acute), 3/12 (acute), 2/12 (sub-acute) and 4/12 (chronic) isolates. Differences in survivorship, parasitaemia progression and PCV were significant (P<0.001) and correlated. The isolate considered to be drug resistant at KALRO-BioRI, KETRI 2538, was confirmed to be resistant to melarsoprol, pentamidine and diminazene aceturate but it was not resistant to suramin. A cure rate of at least 80% was achieved for all test isolates with melarsoprol (1mg/Kg and 20 mg/kg), pentamidine (5 and 20 mg/kg), diminazene aceturate (5 mg/kg) and suramin (5 mg/kg) indicating that the isolates were not resistant to any of the drugs despite the differences in virulence. This study provides evidence of variations in virulence of Tbr clones from a single HAT focus and confirms that this variations is not a significant determinant of isolate sensitivity to anti-trypanosomal drugs.

Highlights

Human African trypanosomiasis (HAT), known as sleeping sickness, is a vector-borne parasitic disease
Our results showed that the clones were distributed among four classes of virulence as follows: 3/12, 3/12, 2/12 and 4/12 isolates
HAT is caused by two species of trypanosomes, namely Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense [1].They are transmitted to humans by tsetse fly (Glossina genus)[2]

Summary

Introduction

Human African trypanosomiasis (HAT), known as sleeping sickness, is a vector-borne parasitic disease. It is caused by infection of humans with protozoan parasites belonging to the genus Trypanosoma. HAT is caused by two species of trypanosomes, namely Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense [1].They are transmitted to humans by tsetse fly (Glossina genus)[2]. Trypanosoma brucei gambiense is found in countries in West and Central Africa and causes a chronic infection [3]. When more evident symptoms emerge, the patient is often already in an advanced disease stage where the central nervous system is affected. Trypanosoma brucei rhodesiense is found in countries in eastern and southern

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Results

Conclusion