Mark Eisler
University of Bristol, Veterinary Sciences, Faculty Member
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Pharmacokinetics of the prophylactic and therapeutic trypanocidal drug isometamidium chloride were examined comprehensively for the first time in cattle using a recently described, highly sensitive ELISA. Cattle were administered single... more
Pharmacokinetics of the prophylactic and therapeutic trypanocidal drug isometamidium chloride were examined comprehensively for the first time in cattle using a recently described, highly sensitive ELISA. Cattle were administered single intravenous (N = 4) or intramuscular (N = 5) doses of isometamidium at a rate of 1.0 mg x kg(-1) body weight. Concentration data were analyzed over at least 14 days (intravenous treatment) or 30 days (intramuscular treatment) using compartmental and noncompartmental methods. After intravenous administration, apparent volumes of the central compartment (mean = 0.695 liter x kg(-1); range = 0.59-0.95) were large, and volumes of distribution at steady-state (mean = 24.5 liter x kg(-1): range = 18.5-39.3) were particularly large. After intramuscular administration, there was considerable individual variability in Cmax (mean = 111 ng x ml(-1); range = 37-197) and other pharmacokinetic parameters. Absorption kinetics seemed to be multifunctional, with fast and slow components; the mean t(max) was only 36 min (range = 20-60), although the mean absorption time was 282 hr, and the mean terminal elimination phase half-life after intramuscular administration (286 hr; range = 215-463) was over twice that after intravenous administration (mean = 135 hr; range = 123-165). The overall absolute bioavailability of intramuscular-administered isometamidium was 65.7%. These findings were consistent with extensive tissue binding at the intramuscular injection site to form a primary depot responsible for most of the prolonged chemoprophylactic effect of isometamidium, and an additional role for significant secondary drug depots formed by tissue binding elsewhere, particularly after intravenous administration.
Research Interests: Pharmacology, Biology, Pharmacokinetics, Medicine, Quality Control, and 15 moreLivestock, HPLC, Pubmed, Animals, Male, Bioavailability, Cattle, Prophylaxis, Route of Administration, Bovine Serum Albumin, Biological Availability, Enzyme Linked Immunosorbent Assay, Area Under Curve, Pharmacology and pharmaceutical sciences, and Cmax
Two enzyme‐linked immunosorbent assays (ELISA) for the determination of homidium in serum of treated cattle have been developed and evaluated. One is a direct competition (Assay 1) and the other an indirect competition assay (Assay 2).... more
Two enzyme‐linked immunosorbent assays (ELISA) for the determination of homidium in serum of treated cattle have been developed and evaluated. One is a direct competition (Assay 1) and the other an indirect competition assay (Assay 2). Both assays are highly sensitive with a limit of detection of 0.1 ng homidium per mL serum. Homidium levels were measurable in serum of cattle for over 2 months following administration of a single intramuscular (i.m.) dose at 1 mg/kg bodyweight. The level of sensitivity afforded by these assays makes them potentially useful tools in the pharmacokinetic evaluation of homidium and for invetigating drug resistance or causes of drug failure. Assay 2 was chosen as being most suitable for further studies.
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The Fulani pastoralists are the custodians of 90% of the Nigerian cattle population and represent a significant component of the Nigerian economy. Participatory epidemiology involves the systematic use of participatory approaches and... more
The Fulani pastoralists are the custodians of 90% of the Nigerian cattle population and represent a significant component of the Nigerian economy. Participatory epidemiology involves the systematic use of participatory approaches and methods to improve the understanding of diseases and provide options for control. We used focus group meeting, disease impact scoring, seasonal calendar and triangulation as participatory epidemiology methods to identify the most important cattle diseases that Fulani pastoralists encounter in Kwara state, North-central Nigeria. Eight diseases/symptoms were collectively identified by the Fulani pastoralists during the focus group meeting and disease impact scoring exercise as most important affecting their cattle. These are: leptospirosis ( Gabi-Gabi), FMD (Chabo), fasciolosis (Hanta), trypanosomiasis (Samore), haematuria (Taki), tick infestation (Duce), brucellosis (Kwanejie) and ear infection (Kune); local names in parentheses. The seasonal calendar cr...
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The clinical, parasitological and molecular diagnosis of bovine trypanosomosis were compared using samples from 250 zebu cattle exposed to natural trypanosome challenge in Uganda. Clinical examination, molecular and parasitological... more
The clinical, parasitological and molecular diagnosis of bovine trypanosomosis were compared using samples from 250 zebu cattle exposed to natural trypanosome challenge in Uganda. Clinical examination, molecular and parasitological diagnoses detected 184 (73.6%), 96 (38.4%) and 36 (14.4%) as diseased, respectively. The sensitivity and specificity of clinical examination were 87.5% and 35%, and 78 % and 27 % based on molecular and parasitological diagnoses, as gold standards, respectively. Of the 33, 3, 13 and 12 parasitological-positive cattle that had Trypanosoma brucei, Trypanosoma congolense, Trypanosoma vivax or mixed infections, 78 %, 33 %, 84 % and 100 % respectively manifested clinical signs. Of the 24, 89, 12, 3, 6 and 27 cattle detected by molecular diagnosis to have mixed infections, T. brucei, T. vivax, T. congolense forest-, Savannah- and Tsavo-type, 100%, 83%, 91%, 100%, 67% and 81 % had clinical signs, respectively. In conclusion, treatment of cattle based on clinical ...
Research Interests: Biology, Kenya, Medicine, Pubmed, Animals, and 15 moreBlood, Diagnosis, ELISA, Polymerase Chain Reaction, Differential Diagnosis, Cattle, Prevalence, Trypanosoma, Trypanosoma brucei brucei, Physical examination, Trypanosomiasis, Sensitivity and Specificity, Clinical Diagnosis, DNA probes, and Trypanosoma vivax
Research Interests: Epidemiology and Medicine
<p>In (a), <b>M</b><b><i><sub>v </sub></i></b>, proportions of each participant diagnosis are shown for each DST diagnosis in columns summating to 1. In (b),... more
<p>In (a), <b>M</b><b><i><sub>v </sub></i></b>, proportions of each participant diagnosis are shown for each DST diagnosis in columns summating to 1. In (b), <b>M</b><b><i><sub>c </sub></i></b>, proportions of each DST diagnosis are shown for each participant diagnosis in columns summating to 1.</p><p>Leading diagonal indicating agreement, other cells indicating disagreement.</p><p><sup>1</sup>NA: not applicable. [Other abbreviations as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0040687#pone-0040687-t004" target="_blank">Table 4</a>.].</p
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<p>NB the DST was available to participants during Phase-2 but not Phase-1.</p><p><sup>1</sup>As <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0040687#pone-0040687-t003"... more
<p>NB the DST was available to participants during Phase-2 but not Phase-1.</p><p><sup>1</sup>As <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0040687#pone-0040687-t003" target="_blank">table 3</a>.</p
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Map and evaluate the effectiveness of food loss and waste reduction interventions in low- and middle-income countries, determine the reduction pathways related to waste prevention, re-use or recycling, and identify social, economic,... more
Map and evaluate the effectiveness of food loss and waste reduction interventions in low- and middle-income countries, determine the reduction pathways related to waste prevention, re-use or recycling, and identify social, economic, environmental and nutritional co-benefits as they relate to the intervention. This will be done by: (i) systematically reviewing scientific and grey literature sources and (ii) conducting meta-analyses by food group where appropriate.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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The Luangwa Valley is recognised as a focus of endemic infection with human sleeping sickness caused by Trypanosoma bruceirhodesiense. Extensive infection of the wildlife population with many species of trypanosome has been identified and... more
The Luangwa Valley is recognised as a focus of endemic infection with human sleeping sickness caused by Trypanosoma bruceirhodesiense. Extensive infection of the wildlife population with many species of trypanosome has been identified and livestock keeping is almost non-existent due to losses from trypanosomiasis and predation by wild animals. The aim of this study was to investigate the ecology of trypanosomiasis in this mult-host wildlife community, relatively free from anthropogenic influences. Particular focus was to be applied to the role of common warthog, phacocoerus aethipicus, within the reservoir community. The thesis initially reviews the history of protected area management in the Luangwa Valley. Remotely sensed imagery is then used in a study of the vegetation units of Luambe National Park. A supervised classification algorithm utilising fuzzy logic is used to generate a land cover classification of the part with an overall accuracy of 71%. Surveys of the tsetse and wild mammal population in Luambe national park are then presented. Data collected from the tsetse survey are analysed using generalised linear models with mixed effects to investigate factors influencing the trypanosome prevalence in tsetse, as well as the distribution and apparent density of tsetse. The density of tyhe host mammal population is assessed using distance sampling techniques and the distribution of warthog burrows mapped. Finally, a cross-sectional survey of trypanosome prevalence in the wild animal population of the Luangwa Valley is described, using novel molecular techniques for diagnosis. Risk factors for infection are analysed using logistic regression analysis and the host distribution for each trypanosome species described
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<p>κ-values for each DST diagnosis in columns are indicated for each participant diagnosis in rows. Main diagonal (mostly boldface numbers) indicating agreement between like diagnoses, other cells indicating possible cross-agreement... more
<p>κ-values for each DST diagnosis in columns are indicated for each participant diagnosis in rows. Main diagonal (mostly boldface numbers) indicating agreement between like diagnoses, other cells indicating possible cross-agreement between differing diagnoses. Boldface numbers indicate at least ‘fair’ agreement (κ ≥0.2); non-bold, positive numbers indicate slight agreement (0.2> κ >0); negative numbers indicate no cross-agreement, i.e. less than that expected by chance.</p><p><sup>1</sup>Other: any participant’s diagnosis other than the eight conditions listed on the DST; a DST diagnosis of ‘other’ resulted when none of its 16 signs was recorded for a case.</p>2<p>SCH: schistosomosis. [Further abbreviations as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0040687#pone-0040687-t003" target="_blank">Table 3</a>.].</p
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Pharmacokinetic studies on the trypanocidal drug homidium bromide using a competitive enzyme immunoassay (detection limit 0.1 ng/mL) are reported for non-infected Friesian and Boran steers following treatment with homidium bromide at a... more
Pharmacokinetic studies on the trypanocidal drug homidium bromide using a competitive enzyme immunoassay (detection limit 0.1 ng/mL) are reported for non-infected Friesian and Boran steers following treatment with homidium bromide at a dose of 1.0 mg/kg b.w. Following intravenous (i.v.) treatment of Friesian steers (n = 5), the mean serum drug concentrations were 31.9 +/- 2.1 and 3.9 +/- 0.4 ng/mL at 1 and 24 h, respectively. The decline in serum drug concentration was tri-exponential with half-lives of 0.064 +/- 0.037 h for t1/2 alpha, 7.17 +/- 1.87 h for t1/2 beta and 106.3 +/- 6.6 h for t1/2 gamma for distribution and elimination phases 1 and 2, respectively. Drug was detectable in serum for 17 days following treatment. The mean residence time (MRT) was 63.4 +/- 7.5 h. Following intramuscular (i.m.) treatment of Friesian steers (n = 5), the drug concentration at 1 h after treatment was 72.5 +/- 2.2 ng/mL. This declined to 9.8 +/- 1.8 ng/mL at 24 h. Low concentrations of between 0.1 and 0.3 ng/mL remained in circulation for up to 90 days post-treatment. Following intramuscular treatment of Boran steers (n = 5), the mean serum drug concentration at 1 h after treatment was 112.1 +/- 40.3 ng/mL. By 24 h after treatment, the concentration had fallen to 13.0 +/- 3.3 ng/mL. Thereafter, the serum drug concentration-versus-time profile and the pharmacokinetic parameters obtained following non-compartmental analysis were similar to those obtained following intramuscular treatment of Friesian steers.
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Research Interests: Microbiology, Quality Control, Animals, Diagnosis, ELISA, and 15 moreFisheries Sciences, Experimental Infection, Goats, Cattle, Trypanosoma brucei, Study design, Immunodiagnosis, Monoclonal Antibody, Sensitivity and Specificity, High Sensitivity, Enzyme Linked Immunosorbent Assay, Antigens, Cohort Studies, Insect Vectors, and Trypanosoma vivax
Research Interests: Microbiology, Geography, Biology, Drug Use, Mice, and 15 moreAnimals, Drug Resistance, Livestock Production, Standardisation, Fisheries Sciences, Domestic Animals, Cattle, Trypanosoma, Trypanosoma brucei brucei, Sub Saharan Africa, Trypanocidal Agents, Enzyme Linked Immunosorbent Assay, Random Allocation, cattle diseases, and disease transmission
Research Interests: Geography, Kenya, Medicine, Animal Husbandry, Seasonality, and 15 moreLivestock, Animals, Animal health, Livestock Production, Data Collection, Participatory Rural Appraisal, Questionnaires, Longitudinal Studies, Longitudinal Study, Chi Square Distribution, Rural Livelihood, Production System, Seasonal change, Rural Population, and Dry Season
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Research Interests: Pharmacokinetics, Kenya, Biological Sciences, Drugs, Animals, and 15 moreDrug Resistance, Male, ELISA, Microbial genetic and drug resistance, Dose rate, Cattle, Bromide, Bos Indicus, Parameters, Sera, Area Under the Curve, Enzyme Linked Immunosorbent Assay, cattle diseases, Medical and Health Sciences, and Peripheral blood
The relationship between serum concentrations of the prophylactic trypanocidal drug isometamidium chloride and protection against tsetse challenge with two populations of Trypanosoma congolense was investigated in Boran (Bos indicus)... more
The relationship between serum concentrations of the prophylactic trypanocidal drug isometamidium chloride and protection against tsetse challenge with two populations of Trypanosoma congolense was investigated in Boran (Bos indicus) cattle, using an isometamidium-ELISA. Isometamidium chloride (Samorin) was administered to cattle at a dose rate of 1.0 mg/kg body weight by deep intramuscular injection. Thereafter, the animals were challenged at monthly intervals with either a drug-sensitive clone (T. congolense IL 1180) or a clone expressing a moderate level of resistance to isometamidium (T. congolense IL 3343). Untreated control cattle were used to confirm the infectivity of each challenge. Of ten drug-treated cattle that were challenged with T. congolense IL 3343, all were refractory to infection at the first challenge. 1 month after drug administration. However, all ten animals succumbed to infection at either the second (seven cattle) or third (three cattle) monthly challenges. By contrast, all five drug-treated cattle challenged with T. congolense IL 1180 resisted four monthly challenges. The mean isometamidium concentration at the time of the first, 1 month, challenge was 5.6 +/- 2.8 ng/ml. At the time of the second monthly challenge the mean concentration was 2.0 +/- 0.86 ng/ml: at this time, concentrations were not significantly different between those cattle refractory to challenge with T. congolense IL 3343 and those cattle that were not. Thus, differences in susceptibility to challenge at this time would appear to be due to differences in the drug sensitivity of the parasite challenge. Finally, the mean isometamidium concentration in uninfected cattle at the time of the fourth monthly challenge was 0.4 +/- 0.18 ng/ml. These results indicate that when T. congolense infection occurs in cattle under isometamidium prophylaxis, the parasites may be considered at least moderately drug resistant if the concentration of isometamidium in serum is 2.0 ng/ml. At concentrations between 0.4 and 2.0 ng/ml a low level of drug resistance may be inferred. Below 0.4 ng/ml, however, no inference regarding drug resistance should be made.
Research Interests: Biology, Medicine, Biological Sciences, Drugs, Animals, and 15 moreDrug Resistance, Microbial genetic and drug resistance, Dose rate, Cattle, Trypanosoma, Body Weight, Trypanosomiasis, Bos Indicus, Trypanocidal Agents, Eliza, Enzyme Linked Immunosorbent Assay, Insect Vectors, Tsetse Flies, blood serum, and Medical and Health Sciences
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Research Interests: Animal Behavior, Zambia, Multidisciplinary, Movement, Female, and 5 moreAnimals, Male, Accelerometry, PLoS one, and Cattle
Endemic zoonoses are found throughout the developing world, wherever people live in close proximity to their animals, affecting not only the health of poor people but often also their livelihoods through the health of their livestock.... more
Endemic zoonoses are found throughout the developing world, wherever people live in close proximity to their animals, affecting not only the health of poor people but often also their livelihoods through the health of their livestock. Unlike newly emerging zoonoses that attract the attention of the developed world, these endemic zoonoses are by comparison neglected. This is, in part, a consequence of under-reporting, resulting in underestimation of their global burden, which in turn artificially downgrades their importance in the eyes of administrators and funding agencies. The development of cheap and effective vaccines is no guarantee that these endemic diseases will be eliminated in the near future. However, simply increasing awareness about their causes and how they may be prevented—often with very simple technologies—could reduce the incidence of many endemic zoonoses. Sustainable control of zoonoses is reliant on surveillance, but, as with other public-sector animal health ser...
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Diagnosis and treatment of endemic infectious disease is crucial for productivity of cattle in rural sub-Saharan Africa, but shortages of trained veterinary professionals necessitate support for less well-trained cadres of animal health... more
Diagnosis and treatment of endemic infectious disease is crucial for productivity of cattle in rural sub-Saharan Africa, but shortages of trained veterinary professionals necessitate support for less well-trained cadres of animal health worker. A Delphi survey of veterinary experts provided quantitative information on key clinical signs associated with eight endemic bovine diseases, then heuristics and dendrogram analysis identified a reduced sign set to be incorporated in a diagnostic decision support tool implemented as a simple colour-banded card. One hundred and seventy disease-sign questionnaire returns were obtained from 32 veterinary research scientists and 14 veterinary practitioners. Preliminary validation of the decision support tool for 16 prototypical cases resulted in ‘correct’ diagnosis over 90% of the time. The card potentially serves as a training aid and aide-mémoire, and could improve the diagnostic competence of animal healthcare providers.
Research Interests: Veterinary Education, Medicine, Animal Husbandry, Infectious Disease, Animals, and 14 moreLivestock Production, Endemic Diseases, Decision support tool, Risk factors, Cattle, Questionnaires, Public health systems and services research, QL, Cambridge University, Sub Saharan Africa, Risk Factors, Severity of Illness Index, Decision Support Techniques, and cattle diseases
Field studies were conducted to assess the occurrence of resistance to isometamidium chloride and diminazene aceturate in trypanosomes infecting cattle in Kénédougou Province of Burkina Faso. Forty-five of the 166 villages in Kénédougou... more
Field studies were conducted to assess the occurrence of resistance to isometamidium chloride and diminazene aceturate in trypanosomes infecting cattle in Kénédougou Province of Burkina Faso. Forty-five of the 166 villages in Kénédougou were randomly sampled and visited to assess livestock numbers, trypanosomosis risk, and tsetse challenge. The proportion of cattle infections associated with drug-resistant trypanosomes was assessed in the nine villages with the highest trypanosome infection prevalence and one village with a confirmed history of drug-resistant infections. These studies showed that resistance to both isometamidium and diminazene was widespread. However, there was considerable variation between villages in drug-resistance parameters, with the proportion of treated cattle with trypanosome infections 3 months after isometamidium prophylaxis varying from 6.9 to 63.8% and the proportion of cattle having infections 2 weeks after treatment with diminazene varying from 0 to 36.8%. The demonstration of widespread resistance to both isometamidium and diminazene has important implications, as administration of trypanocides is the most commonly employed method to control trypanosomosis in this area.
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Univariate analysis of trematode infections in cattle based on household and cattle data in Edu, Kwara State, Nigeria. (XLSX 16 kb)
General characterisitics of households surveyed in Edu LGA, Kwara State. (XLSX 10 kb)
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This unblinding protocol and associated results provide an overview of a blinded randomised controlled trial with open cohort stepped-wedge design conducted at the BBSRC Rothamsted Research North Wyke Farm Platform National Capability... more
This unblinding protocol and associated results provide an overview of a blinded randomised controlled trial with open cohort stepped-wedge design conducted at the BBSRC Rothamsted Research North Wyke Farm Platform National Capability commencing at the start of winter housing of cattle 2016. They are published here in the University of Bristol Data Repository to provide evidence of our study design, objectives, conduct, sample collection and processing, and data analysis prior to unblinding of the study. The unblinding protocol and data are subject to 'Controlled Data Access' and may be accessed upon reasonable request.
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Ruminant livestock are raised under diverse cultural and environmental production systems around the globe. Ruminant livestock can play a critical role in food security by supplying high-quality, nutrient-dense food with little or no... more
Ruminant livestock are raised under diverse cultural and environmental production systems around the globe. Ruminant livestock can play a critical role in food security by supplying high-quality, nutrient-dense food with little or no competition for arable land while simultaneously improving soil health through vital returns of organic matter. However, in the context of climate change and limited land resources, the role of ruminant-based systems is uncertain because of their reputed low efficiency of feed conversion (kilogram of feed required per kilogram of product) and the production of methane as a by-product of enteric fermentation. A growing human population will demand more animal protein, which will put greater pressure on the Earth’s planetary boundaries and contribute further to climate change. Therefore, livestock production globally faces the dual challenges of mitigating emissions and adapting to a changing climate. This requires research-led animal and plant breeding a...
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Cattle are broadly deemed a source of Coxiella burnetii; however, evidence reinforcing their role in human infection is scarce. Most published human Q fever outbreaks relate to exposure to small ruminants, notably goats. Anti-phase II C.... more
Cattle are broadly deemed a source of Coxiella burnetii; however, evidence reinforcing their role in human infection is scarce. Most published human Q fever outbreaks relate to exposure to small ruminants, notably goats. Anti-phase II C. burnetii IgG and IgM were measured by indirect fluorescent antibody tests in 27 farm and veterinary diagnostic laboratory workers to ascertain whether occupational exposure to cattle aborting due to C. burnetii was the probable source of exposure. Four serological profiles were identified on the basis of anti-phase II IgG and IgM titres. Profile 1, characterised by high IgM levels and concurrent, lower IgG titres (3/27; 11.1%); Profile 2, with both isotypes with IgG titres higher than IgM (2/27; 7.4%); Profile 3 with only IgG phase II (5/27; 18.5%); and Profile 4, in which neither IgM nor IgG were detected (17/27; 63.0%). Profiles 1 and 2 are suggestive of recent C. burnetii exposure, most likely 2.5–4.5 months before testing and, hence, during the ...
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This study was conducted to identify risk factors associated with AIV infections in live bird retail stalls (LBRS) in Lahore District, Pakistan. A cross-sectional survey of LBRS was conducted from December 2009-February 2010 using... more
This study was conducted to identify risk factors associated with AIV infections in live bird retail stalls (LBRS) in Lahore District, Pakistan. A cross-sectional survey of LBRS was conducted from December 2009-February 2010 using two-stage cluster sampling based on probability proportional to size. A total of 280 oropharyngeal swab sample pools were collected from 1400 birds in 8 clusters and tested by qRT-PCR for the matrix (M) gene of type A influenza virus and HA gene subtypes H9, H5 and H7. Thirty-four (34) samples were positive for the M gene, of which 28 were also positive for H9. No sample was found positive for H5 or H7. Data for 36 potential risk factors, collected by questionnaire, were analyzed by survey-weighted logistic regression and prevalence odds ratios (OR) for associated risk factors were calculated. A final multivariable model identified three risk factors for H9 infection in LRBS, namely obtaining birds from mixed sources (OR 2.28, CI: 1.4-3.7), keeping birds o...