Title Longitudinal Observational (single cohort) Study on the Causes of Trypanocide Failure in cases of African Animal Trypanosomosis in Cattle Near Wildlife Protected Areas of Northern Tanzania

Abstract

African animal trypanosomosis (AAT) in cattle is primarily managed through trypanocide administration and insecticide application. Trypanocides can be used for both treatment and prophylaxis, but failure is often reported; this may occur due to resistance, substandard drugs, or inappropriate administration. This study in Tanzania aims to quantify reasons for trypanocide failure. An observational year-long longitudinal study was conducted in high-risk AAT areas in Serengeti District from December 2019-October 2022. Purposive sampling targeted herds with high utilization of the prophylactic trypanocide isometamidium chloride (ISM). When a farmer administered a trypanocide (ISM, diminazine aceturate, homidium), the project veterinarian assessed administration and treatment outcomes were determined based on PCR results from blood samples. A multivariable mixed model was utilized to evaluate risk factors for prophylaxis failure. Quality analysis was performed on trypanocide samples using High Performance Liquid Chromatography. A total of 630 cattle from 21 farms were monitored for a year-long period. A total of 295 trypanocide administrations were reported, predominantly being ISM (56%) used for prophylaxis (87%). One-third of trypanocide administrations were not given adequately, and many trypanocides were given to animals that tested negative for trypanosome infections by PCR. Failures occurred in 7% (95% CI 3.0-14%) of curative treatments, and 44% (95% CI 35-42%) of prophylactic administrations. The brand of ISM was significantly associated with odds of prophylaxis failure (p = 0.011). On quality analysis, two ISM samples had no detectable ISM isomers, but the remainder of ISM and DA samples (n=46) fell within the range of acceptable levels. Drug counterfeiting, inadequate use of trypanocides, and resistance are all contributing to trypanocide failure, limiting effective AAT control and with implications for human disease risk. In order to curb trypanocide failure a multi-modal approach to managing the use of trypanocides is required to address all contributing factors. Author SummaryAfrican animal trypanosomosis (AAT) in cattle is commonly controlled through the use of medications called trypanocides. However, these interventions often fail to control AAT due to reasons such as drug resistance, poor-quality medicines, or incorrect administration. This study, conducted in Tanzania between December 2019 and October 2022, aimed to understand why trypanocides fail. Researchers focused particularly on cattle herds that used a preventive drug called isometamidium chloride (ISM). During the study, a veterinarian monitored how farmers administered trypanocides like ISM, diminazine aceturate (DA), or homidium, ensuring proper dosage and storage. Blood samples from cattle were tested to check if treatments were effective. The study found that one-third of trypanocide treatments were not given correctly, and many cattle treated with trypanocides were not actually infected. It was determined that 7% of treatments and 44% of preventive doses failed. The type of ISM brand used played a significant role in failure rates, with some brands performing worse than others. Additionally, tests revealed that some ISM samples lacked the active ingredients necessary for effectiveness. The study highlights that counterfeit drugs, improper use, and drug resistance all contribute to the problem, and a more comprehensive strategy is needed to tackle these issues.