Factors affecting transmission of trypanosomes through tsetse flies

The maintenance of human sleeping sickness and nagana across sub-Saharan Africa depends on cyclical transmission of trypanosomes through tsetse flies. Infection rates in tsetse are normally very low as most parasites ingested with a bloodmeal die in the fly gut. Infections which successfully establish in the fly midgut may subsequently mature into mammalian infective trypanosomes in the salivary glands. However, these processes are not automatic and involve tsetse, symbiont, trypanosome and environmental factors.Previous work showed that the symbiotic bacterium Sodalis glossinidius was involved in susceptibility to trypanosome infection. Streptozotocin (a toxic analogue of the bacterium's main food source) has been recently shown to decrease trypanosome infection rates in the offspring of treated tsetse. In the present work streptozotocin did remove S. glossinidius from the offspring of treated flies but it was not possible to generate a line of tsetse free from 5. glossinidius infection.Other potential factors involved in acquisition of trypanosome infection were then examined. A range of antioxidants or cyclic GMP were shown to prevent trypanosome death in the tsetse midgut. The process was shown to be independent of protein synthesis as D-cysteine (an unphysiological isomer of L-cysteine) also enhanced midgut infection rates. Further experiments showed that cGMP could significantly inhibit trypanosome death when fed up to 96 h post-infection, whereas antioxidants only functioned for 48 h post-infection. Moreover it was found that maturation of established midgut infections could be regulated by environmental stimuli as well as by antioxidants. Cold shock of infected flies as well as addition of L-cysteine but not D-cysteine to the bloodmeal resulted in significant increases in maturation rates, while nitric oxide synthase inhibitors reduced maturation rates.It is concluded that reactive oxygen species play a major role in killing trypanosomes entering the tsetse midgut and that cysteine containing proteins and/or nitric oxide are essential for differentiation of established midgut infections into mammalian infective salivary gland infections

Hard ticks (Acari: Ixodidae) and tick-borne diseases of sheep and goats in Africa: A Review

Ticks are leading vectors of economically important pathogens that affect small ruminants due to favourable climatic conditions across different regions of the African continent. They are responsible for both direct and indirect economic losses in the livestock industry. This review focuses on the species diversity of hard ticks, their biology, tick-borne diseases of sheep and goats including non-infectious disease, and risk factors to tick infestation in Africa. Furthermore, our review provides recent updates on distribution of ticks and tick-borne pathogens of small ruminants in Africa. It was observed that several species and subspecies of hard ticks belonging to the genera Hyalomma (Hy), Rhipicephalus (Rh), Ixodes (I) and Amblyomma (Am) were found infesting small ruminants across the different regions of the continent. Of these genera, Rhipicephalus ticks accounts for the majority of the registered species, with exactly 27 different species infesting small ruminant stocks comprising of different developmental instars and adults of the tick. Rhipicephalus decolaratus, Rh. e. evertsi and Rh. appendiculatus were the three most common Rhipicephalus species reported. Both protozoal (Babesia and Theileria) and bacterial (Anaplasma, Rickettsia, Ehrlichia, Coxiella and Mycoplasma) pathogens have being reported to be amplified in several hard tick species and/or small ruminant hosts. Furthermore, tick paralysis and lameness were non-infectious conditions attributed to tick infestations. Amblyomma hebraeum and Rh. glabroscutatum may cause lameness in goats, while Hy. rufipes is responsible for the same condition in Merino sheep. Host paralysis due to a neurotoxin released by female Rh. e. evertsi and I. rubicundus has been documented within the continent. We therefore advocate for the need of integrated control measures against tick-borne pathogens (TBPs) including their arthropod vectors, to be performed simultaneously to ease the burden of vector-borne diseases in small ruminant production.<br/

Effects of cyclic nucleotides on midgut infections and maturation of T. b. brucei in G. m. morsitans

Cyclic nucleotide signalling through cyclic adenosine monophosphate (cAMP) is thought to play an important role in the transformation of the long slender (dividing) form to the short-stumpy (arrested) form in the mammalian bloodstream but the role of cyclic nucleotides in the tsetse-based part of the trypanosome life cycle is unknown. In a series of in vivo experiments, it was found that cyclic guanosine monophosphate (cGMP) but not cAMP could induce significantly higher rates of midgut infection in tsetse. Continuous feeding of either cGMP or cAMP to tsetse had no effect on rates of maturation of established midgut infections suggesting that these two parts of the life cycle in tsetse are not linked

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

One Health policy for combatting African trypanocide resistance

The rise of African trypanocide resistance (ATr) is influenced by various factors such as evolutionary changes in the pathogen, the presence of resistance genes in the population, poor policy decisions, limited private-public partnerships to engage local communities, and insufficient funding for the development of new drugs over the past sixty years. These challenges have been exacerbated by the inadequate implementation of drug liberalization policies in the mid 20th century, leading to poor pharmacovigilance practices for veterinary drugs in low and middle income countries (LMICs). One health (OH), a disease management framework, provides practical solutions for addressing ATr, drawing on its success in managing previous epidemics like avian influenza in 2004 and the recent COVID-19 pandemic, where institutional collaborations were rapidly established. To combat ATr, OH initiatives involving both international and local partners at the policy and grassroots levels are crucial to generate community interest. The importance of political commitment, media involvement, and nongovernmental organizations cannot be overstated, as they are essential for resource mobilization and long-term sustainability in LMICs.</p

Real-time fully focused imaging with parameter estimation for in-process inspection and manufacturing control

Productivity, schedule, and environment sustainability considerations are driving research and development into in-process inspection and control during fusion welding applications. Ultrasonic inspection using the Total Focusing Method (TFM) has been shown to provide high quality imaging and adaptability to complex scenarios, making it a promising choice for these applications. However, its high computation requirements have thus far limited its use in inprocess inspection and weld control due to tight temporal requirements. Furthermore, in scenarios in which inspection geometry varies over time, as found during in-process weld inspection, focal law computation for each image adds additional delay.This work presents a novel GPU-Accelerated real-time approach for both estimating inspection setup parameters and focal law computation for fully focused imaging. This operates on the same Full Matrix Capture data required for TFM imaging, adding no acquisition latency. The implementation developed is capable of computation rates exceeding the capture rate of FMC, allowing it to operate within the temporal cycle window of welding control and in-process inspection applications

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 amongst 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

Molecular prevalence and distribution of tick-borne bacterial and protozoan pathogens of sheep and goats in Africa: A systematic review and meta-analysis

Tick-borne pathogens (TBPs) are a major impediment to the health, welfare, and production of small ruminants across the world, including Africa. Comprehensive information about the epidemiology of TBPs infecting sheep and goats across Africa is lacking. Therefore, this study was undertaken to determine the prevalence through a meta-analysis of selected TBPs in blood DNA from domestic sheep and goats in Africa obtained using molecular-based methods. The literature review was done according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using 5 English electronic databases (PubMed, Science Direct, Springer Link, Web of Science, and AJOL. The search was performed with no restriction in time through to 18th January 2023. Of the 63 full-text articles subjected to eligibility, only 30 articles met the eligibility criteria and were included in the review. The overall pooled prevalence of selected TBPs varied considerably between host species (sheep vs. goats), with Anaplasma ovis (44.50 vs. 48.40%), Ehrlichia ruminantium (5.50 vs. 2.00%), Coxiella burnetii (4.40 vs. 1.70%), Borrelia theileri in sheep (5.20%), Babesia ovis (1.70% vs. 1.90%), Theileria ovis (40.50% vs 10.00%), T. separata (1.00% vs 1.00%) and T. lestoquardi in sheep (8.40%). However, the prevalence of the selected TBPs was generally higher in sheep compared to goats. Several genetic loci were targeted in the characterization of tick-borne pathogens, such as 16S rDNA, groEL, and msp4 for Anaplasma ovis, pCS20 for Ehrlichia ruminantium, Insertion Sequence (IS1111) for Coxiella burnetii, flaB (flagellin) and 16S rRNA for Borrelia theileri, 5.8S rRNA and 18S rRNA for Babesia/Theileria, as well as the utilization of numerous PCR variants including conventional PCR, nested-PCR, qPCR, LAMP, and RLB. In conclusion, A. ovis was the most widely distributed and prevalent TBP affecting small ruminants within the continent. Hence, this warrants adequate attention towards early diagnosis and treatment of infected animals as well as the control of the tick vectors involved in their transmission

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