Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

Progress towards dog-mediated rabies elimination in PR China: a scoping review.

BACKGROUND: Rabies continues to be a serious threat to global public health endangering people's health and public health safety. In the People's Republic of China, multi-sectoral and comprehensive prevention and control strategies have aimed to extensively curb human rabies transmission. Here, we examine the current state of rabies infection in China, explore strategic interventions put in place in response to WHO's ambition of "Zero rabies deaths by 2030" and critically assess the constraints and feasibility of dog-mediated rabies elimination in China. METHODS: This study analyzed and evaluated the process towards dog-mediated rabies elimination in China from five perspectives: namely, human, dog, policy, challenge, and prospects. Evidence-based data on progress of dog-mediated rabies elimination in China was derived from a number of sources; a literature search was undertaken using PubMed, Web of Science and CNKI databases, distribution data for human rabies cases as derived from the Data-center of the China Public Health Science and policy and document data were obtained from official websites of the relevant China ministries and commissions. RESULTS: The incidence of human rabies cases in China have shown a downward trend year-on-year since 2007. Implementation of a government-led, multi-sectoral "One Health" approach to combating rabies has driven down the total number of rabies deaths nationwide to around 200 in 2020. The number of provincial-level administrative divisions (PLADs) reporting human cases of rabies has also decreased to 21 in 2020, 13 of which reported less than 10 cases. Furthermore, the number of outpatient visits seeking rabies post-exposure prophylaxis has risen dramatically over the past two decades, with demand being 15 times higher than it was initially. There remain however, significant gaps in rabies elimination outcomes across the different regions of China. To date the target of achieving a canine rabies vaccination rate of > 75% has not been met. The challenges of rabies immunization of dogs and dog management in underdeveloped cities and rural areas need to be addressed together with more effective animal surveillance and rabies risk from and too wildlife and livestock. CONCLUSIONS: The Chinese government-led, multi-sectoral "One Health" approach to combating rabies and has made significant progress over the past decade. Development and adoption of more cost-effective One Health strategies can achieve more nationally beneficial rabies elimination outcomes. The ambitious target of "Zero rabies deaths by 2030" can be met through establishment of long-lasting herd immunity in dogs by means of dog mass vaccination campaigns, dog population management, epidemiological surveillance and the application of large-scale oral rabies vaccine to eliminate rabies in wild animals coupled with deployment of cost-effective human post-exposure prophylaxis, and community education.

Trypanocide usage in the cattle belt of southwestern Uganda.

Background: Systematic infrastructure and regulatory weaknesses over many decades, in communities struggling with animal African trypanosomiasis (AAT) would be expected to create an environment that would promote drug misuse and risk development of drug resistance. Here, we explore rural community practices of livestock keepers, livestock extension officers and drug shop attendants to determine whether appropriate practice was being followed in administration of trypanocides and other drugs. Methods: A questionnaire-based survey was undertaken in southwestern Uganda in 2022 involving 451 farmers who kept cattle, sheep or goats and 79 "professionals" who were either livestock extension officers or drug shop attendants. Results: Respondents reported using one or more type of trypanocidal drug on 80.1% of the 451 farms in the last 30 days. Diminazene aceturate was used on around three-quarters of farms, while isometamidium chloride was used on around one-fifth. Homidium bromide was used on less than 1% of farms. Cattle were significantly more likely to be treated with trypanocides than sheep or goats. On around two-thirds of farms, trypanocides were prepared and injected by farmers, with extension officers administering these drugs on most of the other third, especially on cattle farms. Almost all drugs were obtained from privately-owned drug shops. For treatment of AAT with trypanocides, prescription-only medicines were routinely used by farmers without professional supervision and in the absence of a definitive diagnosis. While a far greater proportion of professionals had a better education and had received training on the use of trypanocides than farmers, there was relatively little difference in their ability to use these drugs correctly. Farmers were more likely than professionals to use only DA to treat trypanosomiasis and were more likely to use antibiotics as well as trypanocidal drugs to treat the animal. Furthermore, they estimated, on average, that twice the recommended dose of either diminazene aceturate or isometamidium chloride was needed to treat a hypothetical 400 kg bovine. A minority of both farmers and professionals reported that they observed the recommended withdrawal times following injection of trypanocidal drugs and very few of either group knew the recommended withdrawal times for milk or meat. Only one in six farmers reported using the sanative pair (alternating use of diminazene aceturate and isometamidium chloride), to reduce the risk of drug resistant trypanosome strains emerging, while this approach was more widely used by professionals. Farmers reported using antibiotics more commonly than the professionals, especially in sheep and goats, raising concerns as to overuse and misuse of this critical class of drugs. In addition to using trypanocides, most farmers also reported using a topical veterinary pesticide for the control of ticks and tsetse. On average, farmers spent 12.2% of their income from livestock sales on trypanocides. Conclusion: This study highlights the complexity of issues involved in the fight against AAT using drug treatment. A multistakeholder campaign to increase awareness among farmers, drug shop attendants, and extension workers of the importance of adherence to recommended drug dosing, using the sanative pair and following recommended drug withdrawal guidance would promote best practice, reduce the risk of emergence of resistant strains of trypanosomes, and support enhanced food safety.

Systematic Review and Meta-Analysis on Human African Trypanocide Resistance.

Background Human African trypanocide resistance (HATr) is a challenge for the eradication of Human African Trypansomiaisis (HAT) following the widespread emergence of increased monotherapy drug treatment failures against Trypanosoma brucei gambiense and T. b. rhodesiense that are associated with changes in pathogen receptors. Methods: Electronic searches of 12 databases and 3 Google search websites for human African trypanocide resistance were performed using a keyword search criterion applied to both laboratory and clinical studies. Fifty-one publications were identified and included in this study using the PRISMA checklist. Data were analyzed using RevMan and random effect sizes were computed for the statistics at the 95% confidence interval. Results: Pentamidine/melarsoprol/nifurtimox cross-resistance is associated with loss of the T. brucei adenosine transporter 1/purine 2 gene (TbAT1/P2), aquaglyceroporins (TbAQP) 2 and 3, followed by the high affinity pentamidine melarsoprol transporter (HAPT) 1. In addition, the loss of the amino acid transporter (AAT) 6 is associated with eflornithine resistance. Nifurtimox/eflornithine combination therapy resistance is associated with AAT6 and nitroreductase loss, and high resistance and parasite regrowth is responsible for treatment relapse. In clinical studies, the TbAT1 proportion of total random effects was 68% (95% CI: 38.0−91.6); I2 = 96.99% (95% CI: 94.6−98.3). Treatment failure rates were highest with melarsoprol followed by eflornithine at 41.49% (95% CI: 24.94−59.09) and 6.56% (3.06−11.25) respectively. HATr-resistant phenotypes used in most laboratory experiments demonstrated significantly higher pentamidine resistance than other trypanocides. Conclusion: The emergence of drug resistance across the spectrum of trypanocidal agents that are used to treat HAT is a major threat to the global WHO target to eliminate HAT by 2030. T. brucei strains were largely resistant to diamidines and the use of high trypanocide concentrations in clinical studies have proved fatal in humans. Studies to develop novel chemotherapeutical agents and identify alternative protein targets could help to reduce the emergence and spread of HATr.

Systematic Review and Meta-Analysis on Knowledge Attitude and Practices on African Animal Trypanocide Resistance.

BACKGROUND: African 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.

An Update on African Trypanocide Pharmaceutics and Resistance.

African 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.

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.

Anxiety, Anger and Depression Amongst Low-Income Earners in Southwestern Uganda During the COVID-19 Total Lockdown.

Background: Low-income earners are particularly vulnerable to mental health, consequence of the coronavirus disease 2019 (COVID-19) lockdown restrictions, due to a temporary or permanent loss of income and livelihood, coupled with government-enforced measures of social distancing. This study evaluates the mental health status among low-income earners in southwestern Uganda during the first total COVID-19 lockdown in Uganda. Methods: A cross-sectional descriptive study was undertaken amongst earners whose income falls below the poverty threshold. Two hundred and fifty-three (n = 253) male and female low-income earners between the ages of 18 and 60 years of age were recruited to the study. Modified generalized anxiety disorder (GAD-7), Spielberger's State-Trait Anger Expression Inventory-2 (STAXI-2), and Beck Depression Inventory (BDI) tools as appropriate were used to assess anxiety, anger, and depression respectively among our respondents. Results: Severe anxiety (68.8%) followed by moderate depression (60.5%) and moderate anger (56.9%) were the most common mental health challenges experienced by low-income earners in Bushenyi district. Awareness of mental healthcare increased with the age of respondents in both males and females. A linear relationship was observed with age and depression (r = 0.154, P = 0.014) while positive correlations were observed between anxiety and anger (r = 0.254, P < 0.001); anxiety and depression (r = 0.153, P = 0.015) and anger and depression (r = 0.153, P = 0.015). Conclusion: The study shows the importance of mental health awareness in low resource settings during the current COVID-19 pandemic. Females were identified as persons at risk to mental depression, while anger was highest amongst young males.

COVID-19-Related Mental Health Burdens: Impact of Educational Level and Relationship Status Among Low-Income Earners of Western Uganda.

Objective: The study aimed to investigate the relationship between mental health with the level of education, relationship status, and awareness on mental health among low-income earners in Western Uganda. Methods: This was a cross-sectional descriptive study carried out among 253 participants. Anxiety, anger, and depression were assessed using a modified generalized anxiety disorder (GAD-7), Spielberger's State-Trait Anger Expression Inventory-2, and Beck Depression Inventory item tools, respectively. Results: The majority of our respondents were male (n = 150/253, 59.3), had a secondary level of education (104/253, 41.1), and were single (137/253, 54.2). No formal education and primary education (r2 = 47.4% and 6.4%, respectively) had a negative correlation with awareness of mental health care. In addition, no formal education had a positive correlation with anger and depression (r2 = 1.9% and 0.3%, respectively). Singleness in this study had a negative correlation with awareness of mental health care, anger, and depression (r2 = 1.9, 0.8, and 0.3%, respectively), and a positive correlation with anxiety (r2 = 3.9%). Conclusion: It is evident that education and relationship status influenced awareness on mental health care and mental health state among low-income earners in Western Uganda during the first COVID-19 lockdown. Therefore, policymakers should strengthen social transformation through the proper engagement of low-income earners in this COVID-19 era.

Effects of ß-Blockers on the Sympathetic and Cytokines Storms in Covid-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative virus in the development of coronavirus disease 2019 (Covid-19) pandemic. Respiratory manifestations of SARS-CoV-2 infection such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) leads to hypoxia, oxidative stress, and sympatho-activation and in severe cases leads to sympathetic storm (SS). On the other hand, an exaggerated immune response to the SARS-CoV-2 invasion may lead to uncontrolled release of pro-inflammatory cytokine development of cytokine storm (CS). In Covid-19, there are interactive interactions between CS and SS in the development of multi-organ failure (MOF). Interestingly, cutting the bridge between CS and SS by anti-inflammatory and anti-adrenergic agents may mitigate complications that are induced by SARS-CoV-2 infection in severely affected Covid-19 patients. The potential mechanisms of SS in Covid-19 are through different pathways such as hypoxia, which activate the central sympathetic center through carotid bodies chemosensory input and induced pro-inflammatory cytokines, which cross the blood-brain barrier and activation of the sympathetic center. ß2-receptors signaling pathway play a crucial role in the production of pro-inflammatory cytokines, macrophage activation, and B-cells for the production of antibodies with inflammation exacerbation. ß-blockers have anti-inflammatory effects through reduction release of pro-inflammatory cytokines with inhibition of NF-κB. In conclusion, ß-blockers interrupt this interaction through inhibition of several mediators of CS and SS with prevention development of neural-cytokine loop in SARS-CoV-2 infection. Evidence from this study triggers an idea for future prospective studies to confirm the potential role of ß-blockers in the management of Covid-19.

Spatial analysis of G.f.fuscipes abundance in Uganda using Poisson and Zero-Inflated Poisson regression models.

BACKGROUND: Tsetse flies are the major vectors of human trypanosomiasis of the form Trypanosoma brucei rhodesiense and T.b.gambiense. They are widely spread across the sub-Saharan Africa and rendering a lot of challenges to both human and animal health. This stresses effective agricultural production and productivity in Africa. Delimiting the extent and magnitude of tsetse coverage has been a challenge over decades due to limited resources and unsatisfactory technology. In a bid to overcome these limitations, this study attempted to explore modelling skills that can be applied to spatially estimate tsetse abundance in the country using limited tsetse data and a set of remote-sensed environmental variables. METHODOLOGY: Entomological data for the period 2008-2018 as used in the model were obtained from various sources and systematically assembled using a structured protocol. Data harmonisation for the purposes of responsiveness and matching was carried out. The key tool for tsetse trapping was itemized as pyramidal trap in many instances and biconical trap in others. Based on the spatially explicit assembled data, we ran two regression models; standard Poisson and Zero-Inflated Poisson (ZIP), to explore the associations between tsetse abundance in Uganda and several environmental and climatic covariates. The covariate data were constituted largely by satellite sensor data in form of meteorological and vegetation surrogates in association with elevation and land cover data. We finally used the Zero-Inflated Poisson (ZIP) regression model to predict tsetse abundance due to its superiority over the standard Poisson after model fitting and testing using the Vuong Non-Nested statistic. RESULTS: A total of 1,187 tsetse sampling points were identified and considered as representative for the country. The model results indicated the significance and level of responsiveness of each covariate in influencing tsetse abundance across the study area. Woodland vegetation, elevation, temperature, rainfall, and dry season normalised difference vegetation index (NDVI) were important in determining tsetse abundance and spatial distribution at varied scales. The resultant prediction map shows scaled tsetse abundance with estimated fitted numbers ranging from 0 to 59 flies per trap per day (FTD). Tsetse abundance was found to be largest at low elevations, in areas of high vegetative activity, in game parks, forests and shrubs during the dry season. There was very limited responsiveness of selected predictors to tsetse abundance during the wet season, matching the known fact that tsetse disperse most significantly during wet season. CONCLUSIONS: A methodology was advanced to enable compilation of entomological data for 10 years, which supported the generation of tsetse abundance maps for Uganda through modelling. Our findings indicate the spatial distribution of the G. f. fuscipes as; low 0-5 FTD (48%), medium 5.1-35 FTD (18%) and high 35.1-60 FTD (34%) grounded on seasonality. This approach, amidst entomological data shortages due to limited resources and absence of expertise, can be adopted to enable mapping of the vector to provide better decision support towards designing and implementing targeted tsetse and tsetse-transmitted African trypanosomiasis control strategies.

The Contribution of Community Health Education to Sustainable Control of the Neglected Zoonotic Diseases.

Effective and sustainable control of the Neglected Zoonoses (NZDs) demands a One Health approach. NZDs largely impact on individuals in low- and middle-income countries, disproportionally affecting resource poor communities with poor access to veterinary and human health services and to clean water and which are intrinsically dependent on animals for their livelihoods. Many NZDs in humans can be treated, but treatment is often complex and expensive. Similarly, while tools for prevention of transmission may exist, they are complex and expensive to adopt at the scale required to be effective. The cost of intervention for NZDs is high when compared to the public health benefits alone, but costs are easily outweighed by full cross sector analysis and when monetary and non-monetary benefits to all stakeholders are considered. Education is a key tool, often overlooked in favor of more complex solutions for the control of NZDs. Successful education programs have been targeted to children of school age for Taenia solium in Kenya, schistosomiasis in Nigeria, and soil transmitted helminths in China. A Snakes and Ladders board game, designed to teach children about schistosomiasis and encourage compliance with mass deworming programs, deployed in Nigerian schools, showed a 67% increase in knowledge of praziquantel and 65% of children who had previously rejected treatment requested the drug at school. For soil transmitted helminths in China, presentation of health information in cartoon format rather than in poster format, showed post-assessment knowledge to be 90% higher. With the rise in affordable smart-phone technology, internet access and airtime in communities in low- and middle- income countries e-education is an increasingly attractive proposition as an intervention tool for the NZDs. The Vicious Worm, a computer based educational health tool that has been designed around the prevention of Taenia Solium has shown remarkable efficacy in affected communities in which it has been deployed with participants applying the principles learned in their communities. This review explores the successes and benefits of education as a control tool for the NZDs.

The Rise of SARS-CoV-2 Variants and the Role of Convalescent Plasma Therapy for Management of Infections.

Novel therapies for the treatment of COVID-19 are continuing to emerge as the SARS-Cov-2 pandemic progresses. PCR remains the standard benchmark for initial diagnosis of COVID-19 infection, while advances in immunological profiling are guiding clinical treatment. The SARS-Cov-2 virus has undergone multiple mutations since its emergence in 2019, resulting in changes in virulence that have impacted on disease severity globally. The emergence of more virulent variants of SARS-Cov-2 remains challenging for effective disease control during this pandemic. Major variants identified to date include B.1.1.7, B.1.351; P.1; B.1.617.2; B.1.427; P.2; P.3; B.1.525; and C.37. Globally, large unvaccinated populations increase the risk of more and more variants arising. With successive waves of COVID-19 emerging, strategies that mitigate against community transmission need to be implemented, including increased vaccination coverage. For treatment, convalescent plasma therapy, successfully deployed during recent Ebola outbreaks and for H1N1 influenza, can increase survival rates and improve host responses to viral challenge. Convalescent plasma is rich with cytokines (IL-1ß, IL-2, IL-6, IL-17, and IL-8), CCL2, and TNFα, neutralizing antibodies, and clotting factors essential for the management of SARS-CoV-2 infection. Clinical trials can inform and guide treatment policy, leading to mainstream adoption of convalescent therapy. This review examines the limited number of clinical trials published, to date that have deployed this therapy and explores clinical trials in progress for the treatment of COVID-19.

Epidemiology of Trypanosomiasis in Wildlife-Implications for Humans at the Wildlife Interface in Africa.

While both human and animal trypanosomiasis continue to present as major human and animal public health constraints globally, detailed analyses of trypanosome wildlife reservoir hosts remain sparse. African animal trypanosomiasis (AAT) affects both livestock and wildlife carrying a significant risk of spillover and cross-transmission of species and strains between populations. Increased human activity together with pressure on land resources is increasing wildlife-livestock-human infections. Increasing proximity between human settlements and grazing lands to wildlife reserves and game parks only serves to exacerbate zoonotic risk. Communities living and maintaining livestock on the fringes of wildlife-rich ecosystems require to have in place methods of vector control for prevention of AAT transmission and for the treatment of their livestock. Major Trypanosoma spp. include Trypanosoma brucei rhodesiense, Trypanosoma brucei gambiense, and Trypanosoma cruzi, pathogenic for humans, and Trypanosoma vivax, Trypanosoma congolense, Trypanosoma evansi, Trypanosoma brucei brucei, Trypanosoma dionisii, Trypanosoma thomasbancrofti, Trypanosma elephantis, Trypanosoma vegrandis, Trypanosoma copemani, Trypanosoma irwini, Trypanosoma copemani, Trypanosoma gilletti, Trypanosoma theileri, Trypanosoma godfreyi, Trypansoma simiae, and Trypanosoma (Megatrypanum) pestanai. Wildlife hosts for the trypansomatidae include subfamilies of Bovinae, Suidae, Pantherinae, Equidae, Alcephinae, Cercopithecinae, Crocodilinae, Pteropodidae, Peramelidae, Sigmodontidae, and Meliphagidae. Wildlife species are generally considered tolerant to trypanosome infection following centuries of coexistence of vectors and wildlife hosts. Tolerance is influenced by age, sex, species, and physiological condition and parasite challenge. Cyclic transmission through Glossina species occurs for T. congolense, T. simiae, T. vivax, T. brucei, and T. b. rhodesiense, T. b. gambiense, and within Reduviid bugs for T. cruzi. T. evansi is mechanically transmitted, and T. vixax is also commonly transmitted by biting flies including tsetse. Wildlife animal species serve as long-term reservoirs of infection, but the delicate acquired balance between trypanotolerance and trypanosome challenge can be disrupted by an increase in challenge and/or the introduction of new more virulent species into the ecosystem. There is a need to protect wildlife, animal, and human populations from the infectious consequences of encroachment to preserve and protect these populations. In this review, we explore the ecology and epidemiology of Trypanosoma spp. in wildlife.

Correction: Mathematical modelling and control of African animal trypanosomosis with interacting populations in West Africa-Could biting flies be important in maintaining the disease endemicity?

[This corrects the article DOI: 10.1371/journal.pone.0242435.].

Neurocysticercosis: Current Perspectives on Diagnosis and Management.

Porcine cysticercosis, human taeniasis, and (neuro)cysticercosis are endemic in many low- and middle-income countries (LMIC) where they present a significant health burden to affected communities. Neurocysticercosis (NCC) is one of the leading causes of human epilepsy in many hyperendemic regions in Latin America, Asia, and sub-Saharan Africa. The World Health Organization (WHO) reports an estimated 2.5-8.3 million cases of NCC annually with a disability-adjusted life year (DALY) burden of 2.8 million, but as for all neglected tropical diseases (NTDs), these values are likely to be underestimated. Diagnosis of NCC is complex and most accurately diagnosed using clinical neuroimaging that is unavailable in most hyperendemic regions in LMIC. On January 28, 2021, WHO will launch its road map for the NTDs' "Ending the neglect to attain the Sustainable Development Goals: a road map for neglected tropical diseases 2021-2030." Taeniasis/cysticercosis is targeted for control success considered as steady increase in the number of countries with intensified control in hyperendemic areas [increasing from 2 (3%) in 2020 to 4 (6%) in 2023, to 9 (14%) by 2025, and to 17 (27%) by 2030]. Cross-cutting targets that include 100% access to at least basic water supply, sanitation, and hygiene in areas endemic for NTDs and 75% integrated treatment coverage for preventative chemotherapy will additionally impact on the taeniasis/cysticercosis/NCC complex. With no vaccine available for humans, prevention of infection depends on communication to the public of the life cycle of a complex zoonosis to promote behavior change, underpinned by practical control measures including treatment of human taeniasis and (neuro)cysticercosis with albendazole and praziquantel [widely used as part of the mass drug administration (MDA) deworming programs], surgery where appropriate, and effective vaccination and deworming for pigs supported by meat inspection. Here, we review recent advances in tools and implementation for Taenia solium taeniasis/(neuro)cysticercosis (TSTC) control and milestones on the onward path to elimination.

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.

Molecular epidemiology of anaplasmosis in small ruminants along a human-livestock-wildlife interface in Uganda.

BACKGROUND: Information as regards the epidemiology of the Anaplasmataceae in small ruminants in several low- and middle-income countries is scarce. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Morphological, Molecular Identification and Distribution of Trypanosome-Transmitting Dipterans from Cattle Settlements in Southwest Nigeria.

INTRODUCTION: Glossina spp. (Glossinidae), Tabanus spp. (Tabanidae), Ancala spp. (Tabanidae), Atylotus spp. (Tabanidae) and Stomoxys spp. (Muscidae) are important transmitting vectors of African animal trypanosomosis in sub-Saharan Africa. There is paucity of information on the distribution and identification of these flies in cattle settlements in southwest Nigeria. METHODS: The distribution patterns, genetic variations and diversities of dipteran flies in southwest Nigeria were described and identified using morphological and molecular analysis of the 28S rDNA gene. RESULTS: Of the 13,895 flies examined morphologically between April 2016 and March 2017, tabanids were identified [Tabanus (0.34%), Ancala (0.03%), Atylotus (0.01%), Haematopota (0.014%) and Chrysops (0.11%)]. Two stomoxyine species were identified; Stomoxys niger niger Macquart (45.30%) and Stomoxys calcitrans Linnaeus (17.29%) and two Glossina spp. namely; Glossina p. gambiense Vanderplank, 1911 (0.46%) and Glossina tachinoides Westwood (0.51%) were identified. The identities were further confirmed in a BLAST search using their nucleotide sequences. The median-joining network of the 28S rDNA gene sequences indicated that fly species examined were genetically distinct. The apparent density of all the trapped flies was highest at a mean temperature of 26-28 â„ƒ, humidity > 80% and rainfall of 150-220 mm/month. The distribution of flies was observed to increase as vegetation increased in density and decreased in areas with relatively high human population density (> 100/km2). CONCLUSIONS: The population indices of the 28S rDNA gene of the flies suggest that analysis of nuclear DNA fragments may provide more information on the molecular ecology of these flies. Characterising fly species and assessing their impact are essential in distribution and monitoring AAT spread.