title: Epidemiological studies into the impact of trypanocidal drug resistance on the control of trypanosomiasis in coastal Kenya
Creators: name: Mdachi, Raymond Ellie
Publisher: name: University of Glasgow
Year: 1999

description: This thesis describes epidemiological studies into the impact of trypanocidal drug resistance on the control of trypanosomiasis in coastal Kenya. General introduction into the objectives and location of the studies are described in Chapter 1. Previously published work with emphasis on the use of chemotherapy and chemoprophylaxis in the control of trypanosomiasis, factors associated with development of trypanocidal resistance including existing methods available for determination of drug resistance are reviewed in Chapter 2. Chapter 3 describes the General Material and Methods that were common to all laboratory and field studies reported in the later chapters of this thesis. Chapter 4 describes longitudinal studies into the influence of trypanocidal drug resistance on the efficacy of chemoprophylaxis and chemotherapy in control bovine trypanosomiasis on Galana Ranch in the Coast province of Kenya. Isometamidium prophylaxis studies were conducted over a three-year period between December 1994 and March 1997. In each year, Boran cattle were divided into two groups, isometamidium-treated and sentinel group. There was significant variation of trypanosome challenge over the three-year period. There was evidence that early breakthrough infections particularly T. vivax had some degree of resistance to isometamidium. However, isometamidium prophylaxis was efficacious during the year with relatively low trypanosome challenge. In addition isometamidium prophylaxis was cost effective in spite of drug resistance. Observational studies on trypanosomiasis control using chemoprophylaxis in small holder's dairy cattle are described in Chapter 5. A study covering three-prophylactic periods of three months each was carried out from November 1995 to August 1996 in the Kenyan coast north and south of Mombasa on zero grazing dairy cattle. There was evidence of isometamidium prophylaxis failure, which was attributed to drug resistance, genetic susceptibility or resistance of cattle breed, nutritional status and individual animal variations. Chapter 6 describes longitudinal studies carried out in four different sites in Kwale District from February 1997 to October 1998 to assess the influence of trypanocidal drug resistance on efficacy of chemoprophylaxis and the factors contributing to the efficacy of trypanocidal drugs. In each study site cattle were grouped into two groups, isometamidium-treated and sentinel. There were no significant differences in trypanosome challenge between sites. There was evidence of under dosing and incorrect administration by farmers and trained veterinary personnel. This was associated with trypanocidal drug failure and development of resistance observed in the District. In vivo drug sensitivity tests in mice of T. congolense and in cattle of T. vivax are described in Chapter 7. Factors associated with the viability of stabilates and their infectivity were investigated. The stabilates had been obtained during the studies described in Chapters 4, 5 and 6. Isometamidium treatment had no significant effect on viability and infectivity for mice of trypanosome stabilates. In cattle the route of inoculation of T. vivax had a significant effect on the infectivity of stabilates. Sensitivity tests in mice demonstrated that 87.2 % of T. congolense stabilates from Kwale District expressed multiple resistance to isometamidium chloride and diminazene aceturate. Evidence of T. congolense populations in Kwale District that expressed multiple drug resistance corresponded to trypanocidal drug failure observed in the longitudinal and observational studies reported in early chapters. Finally, Chapter 8 discusses the overall findings of the studies described in this thesis with an emphasis on course of action necessary to minimise the spread and further development of drug resistance. Isometamidium prophylaxis was more efficacious against T. congolense than T. vivax infections. Factors associated with isometamidium prophylaxis failure observed included trypanosome challenge, trypanosome species drug resistance genetic susceptibility or resistance of cattle breed, drug administration, drug dose used and nutrition status.