Browsing by Author "MacLeod, Ewan Thomas"
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Item Molecular Epidemiology of Anaplasmosis in Small Ruminants along a Human-Livestock-Wildlife Interface in Uganda(Heliyon, 2021) Kasozi, Keneth Iceland; Welburn, Susan Christina; Nalumenya, David Paul; Namayanja, Monica; Matama, Kevin; Zalwango, Kelly Katenta; Matovu, Wycliff; Zirintunda, Gerald; Ekou, Justine; Kembabazi, Stellamaris; Mugasa, Claire Mack; Kitibwa, Annah; Tayebwa, Dickson Stuart; Musinguzi, Simon Peter; Mahero, Michael; Ssengendo, Ibrahim; Nanteza, Anne; Matovu, Enock; MacLeod, Ewan ThomasInformation as regards the epidemiology of the Anaplasmataceae in small ruminants in several low- and middle-income countries is scarce. In this study a total of 712 DNA samples collected from small ruminants were analyzed for Anaplasmataceae and Anaplasma ovis using the 16S rRNA and MSP4 genes respectively. Infection risk was assessed by location, sex and age of the animals and qGIS® was used to construct spatial maps. The prevalence of Anaplasmataceae spp was 89.1% (95% CI: 77.5–95.9) and 79.1% (95% CI: 75.9–82.1) in ovines and caprines respectively (RR = 1.1, 95% CI: 1.0–1.3); higher than those previously reported in other eastern African countries. The prevalence of A. ovis was 26.1% and 25.4% for both ovines and caprines respectively with ovines showing significantly higher levels of infection than caprines (P < 0.05). The risk of Anaplasma ovis infections was not affected by age (OR = 1.2, 95% CI: 0.9–1.7) or sex (OR = 1.1, 95% CI: 0.6–2.0). Small ruminants located at the forest edge (<0.3 km) showed higher A. ovis prevalence than those found inland with infections present in the midland regions associated with increased agricultural activity. Anaplasma ovis remains a major challenge for small ruminant husbandry in Uganda and infections are under-reported. Policy efforts to prioritize management of Anaplasmataceae for small ruminant health would promote livestock productivity in vulnerable communities, improving livelihoods and ecosystem health.Item Systematic Review and Meta-Analysis on Knowledge Attitude and Practices on African Animal Trypanocide Resistance(Tropical Medicine and Infectious Disease, 2022) Kasozi, Keneth Iceland; MacLeod, Ewan Thomas; Waiswa, Charles; Mahero, Michael; Ntulume, Ibrahim; Welburn, Susan ChristinaAfrican trypanocide resistance is an emerging public health emergency whose control requires a revisit on farmer’s knowledge, attitudes, and practices in developing countries. African animal trypanocide resistance (AATr) is rife in an environment where drug use and policy decisions are disjointed. The objective of the study was to identify community factors responsible for the development of AATr. This was important since diminazene aceturate (DA), isometamidium chloride (ISM), and homidium bromide (HB) have existed for over 30 years and no new drugs have been provided to farmers. Methods: An electronic keyword search across 12 databases was conducted using a search criterion from 1806 to June 2022. This generated a total of 24 publications, but after removing duplicates, review articles, and nonrelated articles, a total of eight papers were included in the analysis by following the PRISMA checklist. A meta-analysis was conducted on the data extracted and the risk ratio and inverse variance at 95% confidence interval were calculated using RevMan®. Results: All the eight articles in the study showed that DA was the most preferred trypanocide in both West and Eastern Africa. Poor farmer knowledge of AATr and limited drug options were major drivers for trypanocide resistance. In addition, farmer treatments, use of untrained personnel, poor administration, poor dosing, and preparation of trypanocides were major drivers for the development of AATr and similarities were identified in DA and ISM practices (P = 0.13). Conclusions: AATr is spread in developing countries due to a lack of community knowledge, attitudes, and drug-use practices. This situation could be reversed through interdisciplinary collaborations in endemic communities by promoting effective treatments and responsible drug handling.Item An Update on African Trypanocide Pharmaceutics and Resistance(Frontiers in Veterinary Science, 2022) Kasozi, Keneth Iceland; MacLeod, Ewan Thomas; Ntulume, Ibrahim; Welburn, Susan ChristinaAfrican trypanosomiasis is associated with Trypanosoma evansi, T. vivax, T. congolense, and T. brucei pathogens in African animal trypanosomiasis (AAT) while T. b gambiense and T. b rhodesiense are responsible for chronic and acute human African trypanosomiasis (HAT), respectively. Suramin sodium suppresses ATP generation during the glycolytic pathway and is ineffective against T. vivax and T. congolense infections. Resistance to suramin is associated with pathogen altered transport proteins. Melarsoprol binds irreversibly with pyruvate kinase protein sulfhydryl groups and neutralizes enzymes which interrupts the trypanosome ATP generation. Melarsoprol resistance is associated with the adenine-adenosine transporter, P2, due to point mutations within this transporter. Eflornithine is used in combination with nifurtimox. Resistance to eflornithine is caused by the deletion or mutation of TbAAT6 gene which encodes the transmembrane amino acid transporter that delivers eflornithine into the cell, thus loss of transporter protein results in eflornithine resistance. Nifurtimox alone is regarded as a poor trypanocide, however, it is effective in melarsoprol-resistant gHAT patients. Resistance is associated with loss of a single copy of the genes encoding for nitroreductase enzymes. Fexinidazole is recommended for first-stage and non-severe second-stage illnesses in gHAT and resistance is associated with trypanosome bacterial nitroreductases which reduce fexinidazole. In AAT, quinapyramine sulfate interferes with DNA synthesis and suppression of cytoplasmic ribosomal activity in the mitochondria. Quinapyramine sulfate resistance is due to variations in the potential of the parasite's mitochondrial membrane. Pentamidines create cross-links between two adenines at 4–5 pairs apart in adenine-thymine-rich portions of Trypanosoma DNA. It also suppresses type II topoisomerase in the mitochondria of Trypanosoma parasites. Pentamidine resistance is due to loss of mitochondria transport proteins P2 and HAPT1. Diamidines are most effective against Trypanosome brucei group and act via the P2/TbAT1 transporters. Diminazene aceturate resistance is due to mutations that alter the activity of P2, TeDR40 (T. b. evansi). Isometamidium chloride is primarily employed in the early stages of trypanosomiasis and resistance is associated with diminazene resistance. Phenanthridine (homidium bromide, also known as ethidium bromide) acts by a breakdown of the kinetoplast network and homidium resistance is comparable to isometamidium. In humans, the development of resistance and adverse side effects against monotherapies has led to the adoption of nifurtimox-eflornithine combination therapy. Current efforts to develop new prodrug combinations of nifurtimox and eflornithine and nitroimidazole fexinidazole as well as benzoxaborole SCYX-7158 (AN5568) for HAT are in progress while little comparable progress has been done for the development of novel therapies to address trypanocide resistance in AAT.