Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengi adult worms in African cattle

BACKGROUND: Ivermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi. METHODS: Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin (Ivomec(®), Merck and Co. Inc.) at 500 μg/kg or doramectin (Dectamax(®), Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity. RESULTS: There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels. CONCLUSION: These results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds

Diagnostic challenges of brucellosis in humans and livestock in Tanzania: A thematic review

This research article was published by CABI One Health, in 2023Brucellosis is an endemic bacterial zoonosis in Tanzania, and is among the most prioritized zoonotic diseases in the country. Brucellosis affects public health and livestock production in developing countries. Most human and livestock cases are not detected by the existing surveillance systems resulting in significant underestimation of the disease burden, and poor management of human cases by using nonspecific antibiotics may potentially contribute to antimicrobial resistance. To quantify the factors related to underreporting and those associated with the challenges in the diagnosis of brucellosis in Tanzania, search terms including “Brucella” “diagnosis” and “challenges” were used to query in Google search engine and publisher databases such as MEDLINE, PUBMED, NCBI, Springer, Hindawi, and Elsevier. The search parameters were limited to publications between 1995 and 2020. The searches returned 319 publications and grey articles which were screened and 57 were eligible for inclusion in this study. Four main areas were identified that cause underreporting of brucellosis and hinder brucellosis diagnosis: (1) inadequate knowledge of brucellosis among stakeholders in the livestock value chain, (2) limited diagnostic capacity for brucellosis due to unawareness of diagnostic tests and lack of epidemiological background of brucellosis among human and livestock health service workers (3) challenges associated with diagnostic tests, which include unreliable availability of diagnostic tests and unskilled workers, and (4) the uneven distribution of brucellosis surveillance studies in the country. This study suggests that there is a need for (1) training on public health education and brucellosis awareness among stakeholders in the livestock value chain; (2) providing scheduled continuing professional education with regard to brucellosis and other zoonotic diseases to health and livestock workers; (3) future brucellosis surveillance studies must focus on unrepresented regions; and (4) lastly, we recommend that the rose Bengal plate test (RBPT) and competitive enzyme-linked immunosorbent assay (cELISA) should be considered in brucellosis diagnostic schemes as a complementary tool to hasten the implementation of an ongoing national strategy for the prevention and control of brucellosis in humans and livestock in Tanzania. We suggest that these recommendations be considered for inclusion in the national strategy for brucellosis control in Tanzania. One Health Impact Statement Brucellosis is a disease caused by bacteria of genus Brucella and is transmitted from animals to humans. Humans get infected through ingestion of infected animal products but also through contact with bacteria via broken skin or inhalation of aerosolized bacteria particles during culture in the laboratory. Humans working with animals or animal products and laboratory personnel are at higher risk of infection. Tanzania has recently established a One-Health desk in the Prime Minister’s Office to address all matters related to One Health. However, the desk is in the infancy stage, more studies must be done to fill knowledge gaps so that working instruments became realistic. This review provides a synthesis of information that could be used by the One Health desk and other One Health stakeholders in the country on how to improve the existing brucellosis surveillance structures for improvement of One-Health service delivery in the country

Serological Patterns of Brucellosis, Leptospirosis and Q Fever in Bos indicus Cattle in Cameroon

Brucellosis, leptospirosis and Q fever are important infections of livestock causing a range of clinical conditions including abortions and reduced fertility. In addition, they are all important zoonotic infections infecting those who work with livestock and those who consume livestock related products such as milk, producing non-specific symptoms including fever, that are often misdiagnosed and that can lead to severe chronic disease. This study used banked sera from the Adamawa Region of Cameroon to investigate the seroprevalences and distributions of seropositive animals and herds. A classical statistical and a multi-level prevalence modelling approach were compared. The unbiased estimates were 20% of herds were seropositive for Brucella spp. compared to 95% for Leptospira spp. and 68% for Q fever. The within-herd seroprevalences were 16%, 35% and 39% respectively. There was statistical evidence of clustering of seropositive brucellosis and Q fever herds. The modelling approach has the major advantage that estimates of seroprevalence can be adjusted for the sensitivity and specificity of the diagnostic test used and the multi-level structure of the sampling. The study found a low seroprevalence of brucellosis in the Adamawa Region compared to a high proportion of leptospirosis and Q fever seropositive herds. This represents a high risk to the human population as well as potentially having a major impact on animal health and productivity in the region

UMF-078: A modified flubendazole with potent macrofilaricidal activity against Onchocerca ochengi in African cattle

<p>Abstract</p> <p>Background</p> <p>Human onchocerciasis or river blindness, caused by the filarial nematode <it>Onchocerca volvulus</it>, is currently controlled using the microfilaricidal drug, ivermectin. However, ivermectin does not kill adult <it>O. volvulus</it>, and in areas with less than 65% ivermectin coverage of the population, there is no effect on transmission. Therefore, there is still a need for a macrofilaricidal drug. Using the bovine filarial nematode <it>O. ochengi </it>(found naturally in African cattle), the macrofilaricidal efficacy of the modified flubendazole, UMF-078, was investigated.</p> <p>Methods</p> <p>Groups of 3 cows were treated with one of the following regimens: (a) a single dose of UMF-078 at 150 mg/kg intramuscularly (im), (b) 50 mg/kg im, (c) 150 mg/kg intraabomasally (ia), (d) 50 mg/kg ia, or (e) not treated (controls).</p> <p>Results</p> <p>After treatment at 150 mg/kg im, nodule diameter, worm motility and worm viability (as measured by metabolic reduction of tetrazolium to formazan) declined significantly compared with pre-treatment values and concurrent controls. There was abrogation of embryogenesis and death of all adult worms by 24 weeks post-treatment (pt). Animals treated at 50 mg/kg im showed a decline in nodule diameter together with abrogated reproduction, reduced motility, and lower metabolic activity in isolated worms, culminating in approximately 50% worm mortality by 52 weeks pt. Worms removed from animals treated ia were not killed, but exhibited a temporary embryotoxic effect which had waned by 12 weeks pt in the 50 mg/kg ia group and by 24 weeks pt in the 150 mg/kg ia group. These differences could be explained by the different absorption rates and elimination half-lives for each dose and route of administration.</p> <p>Conclusion</p> <p>Although we did not observe any signs of mammalian toxicity in this trial with a single dose, other studies have raised concerns regarding neuro- and genotoxicity. Consequently, further evaluation of this compound has been suspended. Nonetheless, these results validate the molecular target of the benzimidazoles as a promising lead for rational design of macrofilaricidal drugs.</p

A rabies lesson improves rabies knowledge amongst primary school children in Zomba, Malawi

<div><p>Rabies is an important neglected disease, which kills around 59,000 people a year. Over a third of these deaths are in children less than 15 years of age. Almost all human rabies deaths in Africa and Asia are due to bites from infected dogs. Despite the high efficacy of current rabies vaccines, awareness about rabies preventive healthcare is often low in endemic areas. It is therefore common for educational initiatives to be conducted in conjunction with other rabies control activities such as mass dog vaccination, however there are few examples where the efficacy of education activities has been assessed. Here, primary school children in Zomba, Malawi, were given a lesson on rabies biology and preventive healthcare. Subsequently, a mass dog vaccination programme was delivered in the same region. Knowledge and attitudes towards rabies were assessed by a questionnaire before the lesson, immediately after the lesson and 9 weeks later to assess the impact the lesson had on school children’s knowledge and attitudes. This assessment was also undertaken in children who were exposed to the mass dog vaccination programme but did not receive the lesson. Knowledge of rabies and how to be safe around dogs increased following the lesson (both p<0.001), and knowledge remained higher than baseline 9 weeks after the lesson (both p<0.001). Knowledge of rabies and how to be safe around dogs was greater amongst school children who had received the lesson compared to school children who had not received the lesson, but had been exposed to a rabies vaccination campaign in their community (both p<0.001) indicating that the lesson itself was critical in improving knowledge. In summary, we have shown that a short, focused classroom-based lesson on rabies can improve short and medium-term rabies knowledge and attitudes of Malawian schoolchildren.</p></div

Evaluation of three 3ABC ELISAs for foot-and-mouth disease non-structural antibodies using latent class analysis

BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious viral disease of even-toed ungulates. Serological diagnosis/surveillance of FMD presents several problems as there are seven serotypes worldwide and in the event of vaccination it may be necessary to be able to identify FMD infected/exposed animals irrespective of their vaccination status. The recent development of non-structural 3ABC protein (NSP) ELISA tests has greatly advanced sero-diagnosis/surveillance as these tests detect exposure to live virus for any of the seven serotypes of FMD, even in vaccinated populations. This paper analyses the performance of three NSP tests using a Bayesian formulation of the Hui-Walter latent class model to estimate test sensitivity and specificity in the absence of a "gold-standard" test, using sera from a well described cattle population in Cameroon with endemic FMD. RESULTS: The analysis found a high sensitivity and specificity for both the Danish C-ELISA and the World Organisation for Animal Health (O.I.E.) recommended South American I-ELISA. However, the commercial CHEKIT kit, though having high specificity, has very low sensitivity. The results of the study suggests that for NSP ELISAs, latent class models are a useful alternative to the traditional approach of evaluating diagnostic tests against a known "gold-standard" test as imperfections in the "gold-standard" may give biased test characteristics. CONCLUSION: This study demonstrates that when applied to naturally infected zebu cattle managed under extensive rangeland conditions, the FMD ELISAs may not give the same parameter estimates as those generated from experimental studies. The Bayesian approach allows for full posterior probabilities and capture of the uncertainty in the estimates. The implications of an imperfect specificity are important for the design and interpretation of sero-surveillance data and may result in excessive numbers of false positives in low prevalence situations unless a follow-up confirmatory test such as the enzyme linked immunoelectrotransfer blot (EITB) is used

Genetic diversity of Cameroon cattle and a putative genomic map for resistance to bovine tuberculosis

Bovine Tuberculosis (bTB) caused by Mycobacterium bovis is a livestock disease of global economic and public health importance. There are currently no effective vaccines available for livestock and so control relies on animal level surveillance and pasteurization of dairy products. A new alternative control approach is to exploit the genetic variability of the host; recent studies have demonstrated that breeding European taurine cattle, such as Holsteins for increased resistance to bTB is feasible. The utility of such an approach is still unknown for African cattle populations. This study aims to assess genetic variation in bTB resistance and the underlying genomic architecture of cattle in Cameroon. We conducted a cross-sectional study of 2,346 slaughter cattle in Cameroon. Retropharyngeal lymph node samples were collected and cultured on Lowenstein Jensen media and the BACTEC MGIT 960 system, and M. bovis was identified using the Hain® Genotype kits. A total of 153 cattle were positive for M. bovis and were archived along with a random selection of negative samples. In this study, we genotyped archived samples from 212 cattle. Their genomic diversity was characterized using PCA, hierarchical clustering and admixture analysis. We assessed genetic variation in bTB resistance using heritability analysis and compared quantitative trait loci. Previous research on this study population have shown that Fulani cattle are more susceptible to bTB than mixed breeds. However, here we show that these apparent phenotypic differences in breeds are not reflected by clear genomic differences. At the genetic level, both the Fulani and mixed cattle show similar patterns of admixture with evidence of both taurine and indicine ancestry. There was little European taurine introgression within the studied population. Hierarchical clustering showed clusters of cattle that differed in their susceptibility to bTB. Our findings allude to bTB resistance being polygenic in nature. This study highlights the potential for genetic control of bTB in Africa and the need for further research into the genetics of bTB resistance within African cattle populations

Evidence of exposure to C. burnetii among slaughterhouse workers in western Kenya

Q fever, caused by C. burnetii, has been reported in slaughterhouse workers worldwide. The most reported risk factor for seropositivity is the workers' role in the slaughterhouse. This study examined the seroprevalence and risk factors for antibodies to C. burnetii in slaughterhouse workers in western Kenya to fill a data gap relating to this emerging disease in East Africa. Individuals were recruited from all consenting slaughterhouses in the study area between February and November 2012. Information was collected from participating workers regarding demographic data, animals slaughtered and role in the slaughterhouse. Sera samples were screened for antibodies to C. burnetii using a commercial ELISA and risk factors associated with seropositivity were identified using multi-level logistic regression analysis. Slaughterhouse workers (n = 566) were recruited from 84 ruminant slaughterhouses in western Kenya. The seroprevalence of antibodies to C. burnetii was 37.1% (95% Confidence Interval (CI) 33.2–41.2%). The risk factors identified for C. burnetii seropositivity included: male workers compared to female workers, odds ratio (OR) 5.40 (95% CI 1.38–21.22); slaughtering cattle and small ruminants compared to those who only slaughtered cattle, OR 1.52 (95% CI 1.06–2.19). In addition, specific roles in the slaughterhouse were associated with increased odds of being seropositive, including cleaning the slaughterhouse, OR 3.98 (95% CI 1.39–11.43); cleaning the intestines, OR 3.24 (95% CI 1.36–7.73); and flaying the carcass OR 2.63 (95% CI 1.46–4.75) compared to being the slaughterman or foreman. We identified that slaughterhouse workers have a higher seroprevalence of antibodies to C. burnetii compared to published values in the general population from the same area. Slaughterhouse workers therefore represent an occupational risk group in this East African setting. Workers with increased contact with the viscera and fluids are at higher risk for exposure to C. burnetii. Education of workers may reduce transmission, but an alternative approach may be to consider the benefits of vaccination in high-risk groups