African animal trypanocide resistance: A systematic review and meta-analysis.

Background: African animal trypanocide resistance (AATr) continues to undermine global efforts to eliminate the transmission of African trypanosomiasis in endemic communities. The continued lack of new trypanocides has precipitated drug misuse and overuse, thus contributing to the development of the AATr phenotype. In this study, we investigated the threat associated with AATr by using the major globally available chemotherapeutical agents. Methods: A total of seven electronic databases were screened for an article on trypanocide resistance in AATr by using keywords on preclinical and clinical trials with the number of animals with treatment relapse, days taken to relapse, and resistant gene markers using the PRISMA checklist. Data were cleaned using the SR deduplicator and covidence and analyzed using Cochrane RevMan®. Dichotomous outputs were presented using risk ratio (RR), while continuous data were presented using the standardized mean difference (SMD) at a 95% confidence interval. Results: A total of eight publications in which diminazene aceturate (DA), isometamidium chloride (ISM), and homidium chloride/bromide (HB) were identified as the major trypanocides were used. In all preclinical studies, the development of resistance was in the order of HB > ISM > DA. DA vs. ISM (SMD = 0.15, 95% CI: -0.54, 0.83; I 2 = 46%, P = 0.05), DA vs. HB (SMD = 0.96, 95% CI: 0.47, 1.45; I 2 = 0%, P = 0.86), and HB vs. ISM (SMD = -0.41, 95% CI: -0.96, 0.14; I 2 = 5%, P = 0.38) showed multiple cross-resistance. Clinical studies also showed evidence of multi-drug resistance on DA and ISM (RR = 1.01, 95% CI: 0.71-1.43; I 2 = 46%, P = 0.16). To address resistance, most preclinical studies increased the dosage and the treatment time, and this failed to improve the patient's prognosis. Major markers of resistance explored include TbAT1, P1/P2 transporters, folate transporters, such as F-I, F-II, F-III, and polyamine biosynthesis inhibitors. In addition, immunosuppressed hosts favor the development of AATr. Conclusion: AATr is a threat that requires a shift in the current disease control strategies in most developing nations due to inter-species transmission. Multi-drug cross-resistance against the only accessible trypanocides is a major public health risk, justifying the need to revise the policy in developing countries to promote control of African trypanosomiasis.

Molecular survey for tick-borne pathogens and associated risk factors in sheep and goats in Kano Metropolis, Nigeria.

Tick-borne pathogens (TBPs) pose an increased health and productivity risk to livestock in sub-Saharan Africa. Information regarding TBPs infecting small ruminants in Kano metropolis is scarce. Therefore, we investigated the molecular epidemiology of tick-borne pathogens of economic importance from sheep and goats in Kano, Nigeria using Polymerase chain reaction (PCR). A total of 346 blood DNA samples were collected from small ruminants and analyzed for TBPs using PCR and sequencing. Risk of infection was determined for age, sex, breed and animal species. Our results indicate the absence of piroplasmids (Babesia/Theileria) and Rickettsia spp. infections. The overall prevalence for Anaplasma spp. was 9.25% (32/346) with a higher prevalence in goats 13.59% (25/184) compared with sheep 4.32% (7/162). With respect to age of animals, goats >4 years had the highest prevalence of 32.45% (11/37) which differs significantly (P = 0.0059) compared with other age categories. Cross breed goats had a prevalence of 15.63% (5/32) compared with Kano brown breed 14.08 (20/142). Sex significant difference (P = 0.029) was observed in the goats with females having the highest prevalence 20.89% (14/67) compared with males 9.40% (11/117). Furthermore, with regards to sheep, no significant difference (P > 0.05) was observed with respect to age and breed. Finally, no significant difference (P > 0.05) was observed with the prevalence of Anaplasma spp. due to Body condition score (BCS) in both sheep and goats. Conclusively, the occurrence of TBPs in small ruminants is low. Continuous efforts in tick control must be sustained to ensure high productive yield and reduced disease burden associated with TBPs of sheep and goats in Kano metropolis.

A Descriptive-Multivariate Analysis of Community Knowledge, Confidence, and Trust in COVID-19 Clinical Trials among Healthcare Workers in Uganda.

Background-misinformation and mistrust often undermines community vaccine uptake, yet information in rural communities, especially of developing countries, is scarce. This study aimed to identify major challenges associated with coronavirus disease 2019 (COVID-19) vaccine clinical trials among healthcare workers and staff in Uganda. Methods-a rapid exploratory survey was conducted over 5 weeks among 260 respondents (66% male) from healthcare centers across the country using an online questionnaire. Twenty-seven questions assessed knowledge, confidence, and trust scores on COVID-19 vaccine clinical trials from participants in 46 districts in Uganda. Results-we found low levels of knowledge (i.e., confusing COVID-19 with Ebola) with males being more informed than females (OR = 1.5, 95% CI: 0.7-3.0), and mistrust associated with policy decisions to promote herbal treatments in Uganda and the rushed international clinical trials, highlighting challenges for the upcoming Oxford-AstraZeneca vaccinations. Knowledge, confidence and trust scores were higher among the least educated (certificate vs. bachelor degree holders). We also found a high level of skepticism and possible community resistance to DNA recombinant vaccines, such as the Oxford-AstraZeneca vaccine. Preference for herbal treatments (38/260; 14.6%, 95% CI: 10.7-19.3) currently being promoted by the Ugandan government raises major policy concerns. High fear and mistrust for COVID-19 vaccine clinical trials was more common among wealthier participants and more affluent regions of the country. Conclusion-our study found that knowledge, confidence, and trust in COVID-19 vaccines was low among healthcare workers in Uganda, especially those with higher wealth and educational status. There is a need to increase transparency and inclusive participation to address these issues before new trials of COVID-19 vaccines are initiated.