Modelling Multi-Drug Resistance During Chemotherapy Of Animal African Trypanosomiasis In Kwale, Kenya.

Abstract

Multi-drug resistance (MDR) has complicated treatment and control of numerous infectious diseases. The extent and rate of increase of MDR varies widely with different drug-pathogen combinations. Each year, animal African trypanosomiasis (AAT), contributes to high cattle mortality rates throughout sub-Saharan Africa (SSA). Treatment of AAT in SSA is complicated by increasing MDR in trypanosomes. Over reliance on trypanocides and poor treatment practices has ultimately led to the serious negative effects of non-susceptibility to multiple trypanocides. Mathematical models can effectively predict the most judicious trypanocide use, and thereby help to restrict widespread MDR. This study aimed to predict the most effective use of trypanocides in Kwale County, Kenya. This was performed among farming communities of Shimba Hills, an area with high AAT incidence and in close proximity to the Shimba Hills National Reserve that has high vector densities. This involved designing, validating and implementing a compartmental susceptible, exposed, infectious and recovered (SEIR) epidemiological model for simulating trypanosomes transmission in tsetse flies and cattle. A smart mobile phone Health App was developed to collect field data on trypanocide non-susceptibility. Data was collated on a central database and analyzed to determine the mathematical model parameters. This information was coupled with that from laboratory analyses of trypanocide induced gene mutations, and used to develop mathematical models that predict increasing MDR. It demonstrates how trypanocide treatment in cattle influences the tsetse infectivity and transmissibility of drug non-susceptible trypanosome strains. The results show that treatment of all cattle with a combination of two trypanocides was the most optimal treatment strategy to restrict development of MDR to AAT. Furthermore, starting the treatment with the least effective trypanocide and ending with the most effective trypanocide, was an ideal trypanocide prescribing practice. The optimal threshold for mass treatment of infected cattle populations was 80%. This study highlights best practices for communal use of multiple drugs to restrict widespread trypanocide non-susceptibility.