Hepatitis E seroprevalence and risk factors in humans and pig in Ghana.

BACKGROUND: Although Hepatitis E virus (HEV) infection has significant negative impact on the health and wellbeing of underprivileged populations, the burden of HEV in Ghana is still unclear, despite widespread water, sanitation, and hygiene (WASH) related conditions that predispose people to the risk of infection. METHODS: A cross-sectional study was conducted to explore rates of HEV seroprevalence and HEV prevalence, as well as risk factors in humans and domestic pigs in Ghana. These were determined using ELISAs manufactured by Wantai Beijing Biopharmaceuticals, China. The study involved 1365 community members, 105 pig farmers and 474 domestic pigs from four administrative regions of Ghana. RESULTS: Results showed overall seroprevalence and prevalence of 12.4% and 0.7% in community members and 15.2% and 2.9% in pig farmers respectively. There was no significant difference in the seroprevalence between the two groups (Z = 0.851; p = 0.3953). However, the prevalence in pig farmers was significantly higher than in community members (Z = 2.412; p = 0.016). Age (OR = 1.369, CI = 1.243 - 1.508; p = 0.0000), gender (OR = 1.419, CI = 1.101 - 1.991; p = 0.043), and the region of residence (OR = 1.569, CI = 1.348 - 1.827; p = 0.0000) were significant risk factors for HEV seroprevalence in a multivariate regression model. In pigs, overall seroprevalence and prevalence of 62.4% and 5.5% were recorded respectively. A significant difference in seroprevalence was found between confined (6.7%) and free-range pigs (88.3%), (Z = 7.492; p < 0.00001) in the Volta Region. Multivariate logistic regression showed a significant association between seroprevalence and husbandry (OR = 7.051, CI = 3.558- 13.972; p = 0.0000) and region (OR = 4.602, CI = 2.300 - 9.205; p = 0.0000) in pigs in the Volta and Greater Accra Region. CONCLUSION: From this study, HEV is endemic in Ghana with high seroprevalence in humans and pig populations. This underscores the need for awareness creation and action for prevention and control.

Prevalence and control implications of bovine trypanosomes in endemic areas of northern Uganda.

African animal trypanosomiasis (AAT), a disease complex caused by tsetse fly-transmitted Trypanosoma brucei brucei, T. congolense savannah ITS, and T. vivax, continues to inflict heavy losses to the animal industry in terms of decreased livestock production and productivity. Live bait technology and chemotherapy have been used as a control strategy in northern Uganda since 2006 with minimal success. Here, we report the results of a cross-sectional study carried out in Lango subregion, Uganda, to assess the species prevalence of bovine trypanosome in cattle using the internal transcribed spacer (ITS) of trypanosome ribosomal DNA (rDNA). Blood samples were collected from 1090 cattle by ear vein puncture and screened using a single pair of primers designed to amplify ITS ribosomal DNA (rDNA). Our results indicate an overall prevalence of 40.18% (438/1090, 95% CI 30.82-54.51). T. vivax constituted 32.66% (356/1090), T. congolense 2.39% (26/1090), T. brucei 1.28% (14/1090), T. godfreyi 0.09%(1/1090), T. brucei and T. congolense 0.36% (4/1090), T. brucei and T. vivax 1.47% (16/1090), T. vivax and T. congolense 1.65% (18/1090), T. vivax and T. simiae 0.18% (2/1090), and T. vivax and T. godfreyi 0.09% (1/1090) of infections. Over 91.7% of infections involved single species, while 9.5% were mixed infections. Over 90.2% (37/41) of the mixed infections involved T. vivax as one of the species, while 53.7% (22/41) involved T. congolense. The high prevalence of AAT and the continued presence of T. brucei raise public health concerns because of the zoonotic implications. An integrated approach that involves mass treatment of cattle, vector, and animal movement control should be adopted to reduce the risk of both AAT and HAT.

Suspected resistance of Trypanosoma species to diminazene aceturate on a cattle farm in Nigeria.

African animal trypanosomiasis is a major cause of mortality and economic losses for the livestock industry in Nigeria. Chemotherapy has been the most reliable option for cattle herders, and the most commonly found drug on the market is diminazene aceturate. To ascertain the long-term efficacy of this compound, we sampled a cattle herd in Ogun State, Nigeria, 2 months after they were treated with diminazene aceturate. The ITS-PCR results revealed 19 positives for trypanosome DNA out of the 79 samples tested (24.1%, 95% CI 16.0-34.5). Seventeen out of the total 19 positives were Trypanosoma congolense (21.5%, 95% CI 13.9-31.8). Mixed infections were also observed. Therefore, the persistence of bovine trypanosomiasis at this Nigerian cattle farm despite treatment could be due to diminazene aceturate resistant trypanosomes being present in the herd.

Factors associated with persistence of African animal trypanosomiasis in Lango subregion, northern Uganda.

African animal trypanosomiasis (AAT) continues to inflict heavy losses on livestock production especially cattle in terms of decreased production and productivity in Uganda. AAT is a disease complex caused by tsetse fly-transmitted Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense, Trypanosoma congolense, and Trypanosoma vivax. The disease is most important in cattle but also known to cause serious losses in pigs, camels, goats, and sheep. Several control measures including live bait technology, mass treatment of cattle with trypanocidal drugs, and deployment of tsetse traps have been used in the past 10 years, but the problem still persists in some areas. This necessitated an exploration of the factors associated with continued trypanosome infections in cattle, which are also known reservoirs for the zoonotic trypanosomiasis. A structured questionnaire was administered to 286 animal owners from 20 villages purposively selected from Lira, Kole, and Alebtong districts of Lango subregion to obtain information on the factors associated with persistence of infection. Over 50% of the respondents reported trypanosomiasis as a major challenge to their livestock. Land ownership (P = 0.029), type of livestock kept (P = 0.000), disease control strategy employed (P = 0.000), source of drugs (P = 0.046), and drug preparation (P = 0.017) were associated with persistent AAT infection. We recommend continued farmer sensitization on the threat of AAT and the available prevention and control options. The use of isometamidium chloride for prophylaxis against trypanosomiasis is highly recommended. There is also a need to foster qualified private veterinary drug supply in the region.

Practices of cattle keepers of southwest Nigeria in relation to bovine trypanosomosis.

Significant increases in human and livestock populations coupled with agricultural practices have changed the socioeconomic perspectives of livestock diseases. Evaluating the socioeconomic impact of bovine trypanosomosis and its vectors (Glossina, Tabanus and Stomoxys) from the perspective of the livestock owners is of great significance. Participatory rural appraisal was conducted among 209 livestock owners (focus groups) to determine the behavioural practices of animal husbandary to bovine trypanosomosis. In Nigeria, common Trypanosoma species found in cattle are Trypanosoma vivax, Trypanosoma congolense and Trypanosoma brucei. Trypanosomosis peaks were reported by owners to be in the months of March-August. A total of 70.8% (95%CI 64.32-76.56%) cattle owners perceived trypanosomosis as a major disease in their herd, 13.4% (95%CI 9.43-18.68%) practiced transhumance in the wet season and 93.9% (95%CI 88.58-96.92%) make use of trypanocides, and approximately US$ 8.4 million is spent annually on trypanocides in southwest Nigeria livestock industry. About 60.5% (95%CI 51.84-68.48) make use of insecticides against transmitting vectors, and only 1.9% (95%CI 0.75-4.82%) have ever heard of any form of government intervention scheme. Estimated losses ≥ US$ 426 (80-100% loss) can be incurred on a single animal depending on the size and market value. There is significant increase (16.2%, 95%CI 11.15-23.00%, P < 0.05) in the mortality rate of bovine trypanosomosis when compared to other livestock diseases. It will therefore be useful to involve the livestock owners with devising new and integrated measures for reducing the impact of this trypanosomosis.

ZOONOTIC ENCOUNTERS AT THE SLAUGHTERHOUSE: PATHWAYS AND POSSIBILITIES FOR THE CONTROL OF CYSTIC ECHINOCOCCOSIS IN NORTHERN MOROCCO.

This study traces the biosocial dynamics of Echinococcus granulosus - a zoonotic tapeworm spread between dogs, livestock and people - at slaughterhouses in Morocco. One of the most important parasitic zoonoses worldwide, this neglected cestode is responsible for a debilitating, potentially life-threatening, human disease and significant livestock production losses. Transmission can be interrupted, among other ways, by restricting dogs from eating cyst-infected livestock viscera. Recent epidemiological studies in Sidi Kacem province, northern Morocco, found that government-operated slaughterhouses were 'hotspots' for hydatid cysts in livestock and infection in dogs. An ethnographic approach was used to compliment these studies, exploring 'how' and 'why' cysts were being openly discarded. All seven visited slaughterhouses had low levels of hygiene, oversight and infrastructure. This was described locally as perpetuating a sense of 'chaos' that normalized (un)hygienic practices and justified the ignoring of state rules and regulations. However deference to 'poor' infrastructure, both physically and symbolically, served to under-emphasize local institutional logics, which were mediated by prevailing risk perceptions, economic practices and local socio-political norms. These included inter-departmental government relationships, the motivation of veterinary technicians, the political lobbying of butchers and market-based mitigation strategies. The study shows the importance of understanding E. granulosus from a biosocial perspective, and the need for more long-term, participatory and integrated 'One Health' approaches for neglected zoonotic diseases.

Improved productivity and sustainable pastoral systems in an era of insecurity-Fulani herds of the southern Jos Plateau, North-Central Nigeria.

This study investigated the productivity and management of sheep and cattle kept by Fulani pastoralists of Bokkos local government area on the Jos Plateau, North-Central Nigeria. Despite the challenges related to insecurity and restricted access to natural resources, results show large breeding herds with above average productivity and reproductive performance. The management strategy was focused on providing both milk and increased cattle numbers for pastoralists and beef to satisfy the high market demand. High natural herd growth and moderate offtake rates allowed households to maintain herd sizes with a small net increase in cattle numbers. Sheep productivity in these herds was characterised by high births, high mortality and high offtake, leading to overall negative herd growth. The use of hired herders is on the rise in response to natural resource conflict, insecurity and reduced family labour availability due to alternative livelihood strategies. Disease and related mortality remain significant constraints to productivity which could be addressed by increased access to quality veterinary care. However, any further increases in livestock numbers would put additional strain on already inadequate natural resources.

Modelling the use of insecticide-treated cattle to control tsetse and Trypanosoma brucei rhodesiense in a multi-host population.

We present a mathematical model for the transmission of Trypanosoma brucei rhodesiense by tsetse vectors to a multi-host population. To control tsetse and T. b. rhodesiense, a proportion, ψ, of cattle (one of the hosts considered in the model) is taken to be kept on treatment with insecticides. Analytical expressions are obtained for the basic reproduction number, R0n in the absence, and R(0n)(T) in the presence of insecticide-treated cattle (ITC). Stability analysis of the disease-free equilibrium was carried out for the case when there is one vertebrate host untreated with insecticide. By considering three vertebrate hosts (cattle, humans and wildlife) the sensitivity analysis was carried out on the basic reproduction number (R(0n)(T)) in the absence and presence of ITC. The results show that R(03)(T) is more sensitive to changes in the tsetse mortality. The model is then used to study the control of tsetse and T. b. rhodesiense in humans through application insecticides to cattle either over the whole-body or to restricted areas of the body known to be favoured tsetse feeding sites. Numerical results show that while both ITC strategies result in decreases in tsetse density and in the incidence of T. b. rhodesiense in humans, the restricted application technique results in improved cost-effectiveness, providing a cheap, safe, environmentally friendly and farmer based strategy for the control of vectors and T. b. rhodesiense in humans.

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.

An exploratory GIS-based method to identify and characterise landscapes with an elevated epidemiological risk of Rhodesian human African trypanosomiasis.

BACKGROUND: Specific land cover types and activities have been correlated with Trypanosoma brucei rhodesiense distributions, indicating the importance of landscape for epidemiological risk. However, methods proposed to identify specific areas with elevated epidemiological risk (i.e. where transmission is more likely to occur) tend to be costly and time consuming. This paper proposes an exploratory spatial analysis using geo-referenced human African trypanosomiasis (HAT) cases and matched controls from Serere hospital, Uganda (December 1998 to November 2002) to identify areas with an elevated epidemiological risk of HAT. METHODS: Buffers 3 km from each case and control were used to represent areas in which village inhabitants would carry out their daily activities. It was hypothesised that the selection of areas where several case village buffers overlapped would enable the identification of locations with increased risk of HAT transmission, as these areas were more likely to be frequented by HAT cases in several surrounding villages. The landscape within these overlap areas should more closely relate to the environment in which transmission occurs as opposed to using the full buffer areas. The analysis was carried out for each of four annual periods, for both cases and controls, using a series of threshold values (number of overlapping buffers), including a threshold of one, which represented the benchmark (e.g. use of the full buffer area as opposed to the overlap areas). RESULTS: A greater proportion of the overlap areas for cases consisted of seasonally flooding grassland and lake fringe swamp, than the control overlap areas, correlating well with the preferred habitat of the predominant tsetse species within the study area (Glossina fuscipes fuscipes). The use of overlap areas also resulted in a greater difference between case and control landscapes, when compared with the benchmark (using the full buffer area). CONCLUSIONS: These results indicate that the overlap analysis has enabled the selection of areas more likely to represent epidemiological risk zones than similar analyses using full buffer areas. The identification of potential epidemiological risk zones using this method requires fewer data than other proposed methods and further development may provide vital information for the targeting of control measures.

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.

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.

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.

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.

Healthcare Management of Human African Trypanosomiasis Cases in the Eastern, Muchinga and Lusaka Provinces of Zambia.

Human African trypanosomiasis (HAT) is a neglected tropical disease that has not received much attention in Zambia and most of the countries in which it occurs. In this study, we assessed the adequacy of the healthcare delivery system in diagnosis and management of rHAT cases, the environmental factors associated with transmission, the population at risk and the geographical location of rHAT cases. Structured questionnaires, focus group discussions and key informant interviews were conducted among the affected communities and health workers. The study identified 64 cases of rHAT, of which 26 were identified through active surveillance and 38 through passive surveillance. We identified a significant association between knowledge of the vector for rHAT and knowledge of rHAT transmission (p < 0.028). In all four districts, late or poor diagnosis occurred due to a lack of qualified laboratory technicians and diagnostic equipment. This study reveals that the current Zambian healthcare system is not able to adequately handle rHAT cases. Targeted policies to improve staff training in rHAT disease detection and management are needed to ensure that sustainable elimination of this public health problem is achieved in line with global targets.

Herd prevalence of bovine brucellosis and analysis of risk factors in cattle in urban and peri-urban areas of the Kampala economic zone, Uganda.

BACKGROUND: Human brucellosis has been found to be prevalent in the urban areas of Kampala, the capital city of Uganda. A cross-sectional study was designed to generate precise information on the prevalence of brucellosis in cattle and risk factors for the disease in its urban and peri-urban dairy farming systems. RESULTS: The adjusted herd prevalence of brucellosis was 6.5% (11/177, 95% CI: 3.6%-10.0%) and the adjusted individual animal prevalence was 5.0% (21/423, 95% CI: 2.7%-9.3%) based on diagnosis using commercial kits of the competitive enzyme-linked immunosorbent assay (CELISA) for Brucella abortus antibodies. Mean within-herd prevalence was found to be 25.9% (95% CI: 9.7%-53.1%) and brucellosis prevalence in an infected herd ranged from 9.1% to 50%. A risk factor could not be identified at the animal level but two risk factors were identified at the herd level: large herd size and history of abortion. The mean number of milking cows in a free-grazing herd (5.0) was significantly larger than a herd with a movement restricted (1.7, p < 0.001). CONCLUSIONS: Vaccination should be targeted at commercial large-scale farms with free-grazing farming to control brucellosis in cattle in and around Kampala city.

Spatial epidemiology of hospital-diagnosed brucellosis in Kampala, Uganda.

BACKGROUND: A retrospective case-control study was undertaken to examine the spatial risk factors for human brucellosis in Kampala, Uganda. METHODS: Information on age, sex and month of diagnosis was derived from records from plate agglutination tests undertaken at Mulago Hospital, Kampala. Information on Parishes (LC2s) where patients reside was sourced from the outpatient registration book. In-patient fracture cases were selected for use as controls using 1:1 matching based on the age, sex and month of diagnosis. The locations of cases and controls were obtained by calculating Cartesian coordinates of the centroids of Parish level (LC2) polygons and a spatial scan statistic was applied to test for disease clustering. Parishes were classified according to the level of urbanization as urban, peri-urban or rural. RESULTS: Significantly more females than males were found to show sero-positivity for brucellosis when compared with the sex ratio of total outpatients, in addition female brucellosis patients were found to be significantly older than the male patients. Spatial clustering of brucellosis cases was observed including around Mulago Hospital (radius = 6.8 km, p = 0.001). The influence of proximity to the hospital that was observed for brucellosis cases was not significantly different from that observed in the controls. The disease cluster was confounded by the different catchment areas between cases and controls. The level of urbanization was not associated with the incidence of brucellosis but living in a slum area was a significant risk factor among urban dwellers (odds ratio 1.97, 95% CI: 1.10-3.61). CONCLUSIONS: Being female was observed to be a risk factor for brucellosis sero-positvity and among urban dwellers, living in slum areas was also a risk factor although the overall risk was not different among urban, peri-urban and rural areas of the Kampala economic zone.

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.