SUNScholar - Browsing by Author "Miller, Michele Ann"

Browsing by Author "Miller, Michele Ann"

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Animal-adapted members of the Mycobacterium tuberculosis complex endemic to the southern African subregion
(AOSIS Publishing, 2016-04) Clarke, Charlene; Van Helden, Paul; Miller, Michele Ann; Parsons, Sven
Members of the Mycobacterium tuberculosis complex (MTC) cause tuberculosis (TB) in both animals and humans. In this article, three animal-adapted MTC strains that are endemic to the southern African subregion – that is, Mycobacterium suricattae, Mycobacterium mungi, and the dassie bacillus – are reviewed with a focus on clinical and pathological presentations, geographic distribution, genotyping methods, diagnostic tools and evolution. Moreover, factors influencing the transmission and establishment of TB pathogens in novel host populations, including ecological, immunological and genetic factors of both the host and pathogen, are discussed. The risks associated with these infections are currently unknown and further studies will be required for greater understanding of this disease in the context of the southern African ecosystem.
Butorphanol with oxygen insufflation corrects etorphine-induced hypoxaemia in chemically immobilized white rhinoceros (Ceratotherium simum)
(BioMed Central, 2014) Haw, Anna; Hofmeyr, Markus; Fuller, Andrea; Buss, Peter E.; Miller, Michele Ann; Fleming, Gregory; Meyer, Leith
Background: Opioid-induced immobilization is associated with severe respiratory depression in the white rhinoceros. We evaluated the efficacy of butorphanol and oxygen insufflation in alleviating opioid-induced respiratory depression in eight boma-managed rhinoceros. Results: Chemical immobilization with etorphine, azaperone and hyaluronidase, as per standard procedure for the white rhinoceros, caused severe respiratory depression with hypoxaemia (PaO2 = 27 ± 7 mmHg [mean ± SD]), hypercapnia (PaCO2 = 82 ± 6 mmHg) and acidosis (pH =7.26 ± 0.02) in the control trial at 5 min. Compared to pre-intervention values, butorphanol administration (without oxygen) improved the PaO2 (60 ± 3 mmHg, F(3,21) =151.9, p <0.001), PaCO2 (67 ± 4 mmHg, F(3,21) =22.57, p <0.001) and pH (7.31 ± 0.06, F(3,21) =27.60, p <0.001), while oxygen insufflation alone exacerbated the hypercapnia (123 ± 20 mmHg, F(3,21) =50.13, p <0.001) and acidosis (7.12 ± 0.07, F(3,21) =110.6, p <0.001). Surprisingly, butorphanol combined with oxygen fully corrected the opioid-induced hypoxaemia (PaO2 = 155 ± 53 mmHg) and reduced the hypercapnia over the whole immobilization period (p <0.05, areas under the curves) compared to the control trial. However, this intervention (butorphanol + oxygen) did not have any effect on the arterial pH. Conclusions: Oxygen insufflation combined with a single intravenous dose of butorphanol improved the immobilization quality of boma-managed white rhinoceros by correcting the opioid-induced hypoxaemia, but did not completely reverse all components of respiratory depression. The efficacy of this intervention in reducing respiratory depression in field-captured animals remains to be determined.
Butorphanol with oxygen insufflation improves cardiorespiratory function in field-immobilised white rhinoceros (Ceratotherium simum)
(AOSIS Publishing, 2015-08-12) Haw, Anna; Hofmeyr, Markus; Fuller, Andrea; Buss, Peter E.; Miller, Michele Ann; Fleming, Gregory; Meyer, Leith
Opioid-induced immobilisation results in severe respiratory compromise in the white rhinoceros (Ceratotherium simum). The effectiveness of oxygen insufflation combined with butorphanol in alleviating respiratory depression in free-ranging chemically immobilised white rhinoceroses was investigated. In this prospective intervention study 14 freeranging white rhinoceroses were immobilised with a combination of etorphine, azaperone and hyaluronidase. Six minutes (min) after the animals became recumbent, intravenous butorphanol was administered and oxygen insufflation was initiated. Previous boma trial results were used for comparison, using repeated measures two-way analysis of variance. The initial immobilisation-induced hypoxaemia in free-ranging rhinoceroses (arterial partial pressure of oxygen [PaO2] 35.4 mmHg ± 6.6 mmHg) was similar to that observed in bomaconfined rhinoceroses (PaO2 31 mmHg ± 6 mmHg, n = 8). Although the initial hypercapnia (PaCO2 63.0 mmHg ± 7.5 mmHg) was not as severe as that in animals in the boma trial (79 mmHg ± 7 mmHg), the field-immobilised rhinoceroses were more acidaemic (pH 7.10 ± 0.14) at the beginning of the immobilisation compared with boma-immobilised rhinoceroses (pH 7.28 ± 0.04). Compared with pre-intervention values, butorphanol with oxygen insufflation improved the PaO2 (81.2 mmHg ± 23.7 mmHg, p < 0.001, 5 min vs 20 min), arterial partial pressure of carbon dioxide (55.3 mmHg ± 5.2 mmHg, p < 0.01, 5 min vs 20 min), pH (7.17 ± 0.11, p < 0.001, 5 min vs 20 min), heart rate (78 breaths/min ± 20 breaths/min, p < 0.001, 5 min vs 20 min) and mean arterial blood pressure (105 mmHg ± 14 mmHg, p < 0.01, 5 min vs 20 min). Oxygen insufflation combined with a single intravenous dose of butorphanol improved oxygenation and reduced hypercapnia and acidaemia in immobilised free-ranging white rhinoceroses.
Development and evaluation of a diagnostic cytokine-release assay for mycobacterium suricattae infection in meerkats (Suricata suricatta)
(BioMed Central, 2017-01-04) Clarke, Charlene; Patterson, Stuart James; Drewe, Julian Ashley; Van Helden, Paul David; Miller, Michele Ann; Parsons, Sven David Charles
Background: Sensitive diagnostic tools are necessary for the detection of Mycobacterium suricattae infection in meerkats (Suricata suricatta) in order to more clearly understand the epidemiology of tuberculosis and the ecological consequences of the disease in this species. We therefore aimed to develop a cytokine release assay to measure antigen-specific cell-mediated immune responses of meerkats. Results: Enzyme-linked immunosorbent assays (ELISAs) were evaluated for the detection of interferon-gamma (IFN-γ) and IFN-γ inducible protein 10 (IP-10) in meerkat plasma. An IP-10 ELISA was selected to measure the release of this cytokine in whole blood in response to Bovigam® PC-HP Stimulating Antigen, a commercial peptide pool of M. bovis antigens. Using this protocol, captive meerkats with no known M. suricattae exposure (n = 10) were tested and results were used to define a diagnostic cut off value (mean plus 2 standard deviations). This IP-10 release assay (IPRA) was then evaluated in free-living meerkats with known M. suricattae exposure, categorized as having either a low, moderate or high risk of infection with this pathogen. In each category, respectively, 24.7%, 27.3% and 82.4% of animals tested IPRA-positive. The odds of an animal testing positive was 14.0 times greater for animals with a high risk of M. suricattae infection compared to animals with a low risk. Conclusion: These results support the use of this assay as a measure of M. suricattae exposure in meerkat populations. Ongoing longitudinal studies aim to evaluate the value of the IPRA as a diagnostic test of M. suricattae infection in individual animals.
Epidemiology of tuberculosis in multi-host wildlife systems : implications for black (diceros bicornis) and white (ceratotherium simum) rhinoceros
(Frontiers Media, 2020) Dwyer, Rebecca A.; Witte, Carmel; Buss, Peter E.; Goosen, Wynand J.; Miller, Michele Ann
Cases of tuberculosis (TB) resulting from infection with Mycobacterium tuberculosis complex (MTBC) have been recorded in captive white (Ceratotherium simum) and black (Diceros bicornis) rhinoceros. More recently, cases have been documented in free-ranging populations of both species in bovine tuberculosis (bTB) endemic areas of South Africa. There is limited information on risk factors and transmission patterns for MTBC infections in African rhinoceros, however, extrapolation from literature on MTBC infections in other species and multi-host systems provides a foundation for understanding TB epidemiology in rhinoceros species. Current diagnostic tests include blood-based immunoassays but distinguishing between subclinical and active infections remains challenging due to the lack of diagnostic techniques. In other species, demographic risk factors for MTBC infection include sex and age, where males and adults are generally at higher risk than females and younger individuals. Limited available historical information reflects similar age- and sex-associated patterns for TB in captive black and white rhinoceros, with more reports of MTBC-associated disease in black rhinoceros than in white rhinoceros. The degree of MTBC exposure in susceptible wildlife depends on their level of interaction, either directly with other infected individuals or indirectly through MTBC contaminated environments, which is dependent on the presence and abundance of infected reservoir hosts and the amount of MTBC shed in their excreta. Captive African rhinoceros have shown evidence of MTBC shedding, and although infection levels are low in free-ranging rhinoceros, there is a risk for intraspecies transmission. Free-ranging rhinoceros in bTB endemic areas may be exposed to MTBC from other infected host species, such as the African buffalo (Syncerus caffer) and greater kudu (Tragelaphus strepsiceros), through shared environmental niches, and resource co-utilization. This review describes current knowledge and information gaps regarding the epidemiology of TB in African rhinoceros.
Experimental Mycobacterium bovis infection in three white rhinoceroses (Ceratotherium simum) : Susceptibility, clinical and anatomical pathology
(Public Library of Science, 2017) Michel, Anita L.; Lane, Emily P.; De Klerk-Lorist, Lin-Mari; Hofmeyr, Markus; Van Der Heijden, Elisabeth M. D. L.; Botha, Louise; Van Helden, Paul; Miller, Michele Ann; Buss, Peter E.
Tuberculosis caused by Mycobacterium bovis is endemic in the African buffalo (Syncerus caffer) population in the Kruger National Park and other conservation areas in South Africa. The disease has been diagnosed in a total of 21 free ranging or semi-free ranging wildlife species in the country with highly variable presentations in terms of clinical signs as well as severity and distribution of tuberculous lesions. Most species are spillover or dead-end hosts without significant role in the epidemiology of the disease. White rhinoceroses (Ceratotherium simum) are translocated from the Kruger National Park in substantial numbers every year and a clear understanding of their risk to manifest overt tuberculosis disease and to serve as source of infection to other species is required. We report the findings of experimental infection of three white rhinoceroses with a moderately low dose of a virulent field isolate of Mycobacterium bovis. None of the animals developed clinical signs or disseminated disease. The susceptibility of the white rhinoceros to bovine tuberculosis was confirmed by successful experimental infection based on the ante mortem isolation of M. bovis from the respiratory tract of one rhinoceros, the presence of acid-fast organisms and necrotizing granulomatous lesions in the tracheobronchial lymph nodes and the detection of M. bovis genetic material by PCR in the lungs of two animals.
Housing and demographic risk factors impacting foot and musculoskeletal health in African Elephants [loxodonta Africana] and Asian elephants [elephas maximus] in North American zoos
(Public Library of Science, 2016) Miller, Michele Ann; Hogan, Jennifer N.; Meehan, Cheryl L.
For more than three decades, foot and musculoskeletal conditions have been documented among both Asian [Elephas maximus] and African [Loxodonta africana] elephants in zoos. Although environmental factors have been hypothesized to play a contributing role in the development of foot and musculoskeletal pathology, there is a paucity of evidence-based research assessing risk. We investigated the associations between foot and musculoskeletal health conditions with demographic characteristics, space, flooring, exercise, enrichment, and body condition for elephants housed in North American zoos during 2012. Clinical examinations and medical records were used to assess health indicators and provide scores to quantitate conditions. Using multivariable regression models, associations were found between foot health and age [P value = 0.076; Odds Ratio = 1.018], time spent on hard substrates [P value = 0.022; Odds Ratio = 1.014], space experienced during the night [P value = 0.041; Odds Ratio = 1.008], and percent of time spent in indoor/outdoor exhibits during the day [P value < 0.001; Odds Ratio = 1.003]. Similarly, the main risk factors for musculoskeletal disorders included time on hard substrate [P value = 0.002; Odds Ratio = 1.050] and space experienced in indoor/outdoor exhibits [P value = 0.039; Odds Ratio = 1.037]. These results suggest that facility and management changes that decrease time spent on hard substrates will improve elephant welfare through better foot and musculoskeletal health.
The kinetics of the humoral and interferon-gamma immune responses to experimental Mycobacterium bovis infection in the white rhinoceros (Ceratotherium simum)
(Frontiers, 2017-12) Parsons, Sven D. C.; Morar-Leather, Darshana; Buss, Peter E.; Hofmeyr, Jennifer; McFadyen, Ross; Rutten, Victor P. M. G.; Van Helden, Paul D.; Miller, Michele Ann; Michel, Anita Luise
ENGLISH ABSTRACT: Mycobacterium bovis is the cause of tuberculosis (TB) in a wide range of species, including white rhinoceroses (Ceratotherium simum). Control of the disease relies on the indirect detection of infection by measuring pathogen-specific responses of the host. These are poorly described in the white rhinoceros and this study aimed to characterize the kinetics of immune responses to M. bovis infection in this species. Three white rhinoceroses were infected with M. bovis and their immune sensitization to this pathogen was measured monthly for 20 months. Cell-mediated immunity was characterized in whole blood samples as the differential release of interferon-gamma in response to bovine purified protein derivative (PPDb) and avian PPD (PPDa) as well as the release of this cytokine in response to the M. bovis proteins 6 kDa early secretory antigenic target (ESAT-6)/10 kDa culture filtrate protein (CFP-10). Humoral immunity was quantified as the occurrence or the magnitude of antibody responses to the proteins ESAT-6/CFP-10, MPB83, MPB83/MPB70, and PPDb. The magnitude and duration of immune reactivity varied between individuals; however, peak responses to these antigens were detected in all animals circa 5–9 months postinfection. Hereafter, they gradually declined to low or undetectable levels. This pattern was associated with limited TB-like pathology at postmortem examination and appeared to reflect the control of M. bovis infection following the development of the adaptive immune response. Measurement of these markers could prove useful for assessing the disease status or treatment of naturally infected animals. Moreover, immune responses identified in this study might be used to detect infection; however, further studies are required to confirm their diagnostic utility.
Measuring antigen-specific responses in Mycobacterium bovis-infected warthogs (Phacochoerus africanus) using the intradermal tuberculin test
(BMC (part of Springer Nature), 2018) Roos, Eduard O.; Olea-Popelka, Francisco; Buss, Peter E.; Hausler, Guy; Warren, Robin M.; Van Helden, Paul D.; Parsons, Sven D. C.; De Klerk-Lorist, Lin-Mari; Miller, Michele Ann
Background: Bovine tuberculosis (bTB) caused by Mycobacterium bovis has previously been diagnosed in warthogs and infection can be highly prevalent (> 30%) in endemic areas. Thus, warthogs could potentially be an important species to consider as sentinels for disease surveillance. However, disease surveillance is dependent on availability of accurate diagnostic assays and only a few diagnostic tests have been investigated for warthogs. Furthermore, the tests that have been used in this species require laboratory equipment and trained personnel to obtain results. Therefore, this study investigated the use of the intradermal tuberculin test (ITT) to screen warthogs for bTB, which can be done with minimal equipment and under field conditions by most veterinarians and other qualified professionals. Changes in skin fold thickness measurements at the bovine purified protein derivative (PPD) administration site, between 0 and 72 h, were compared with differential changes between the bovine and avian PPD sites, for 34 warthogs, to evaluate the performance when different interpretation criteria for the ITT was used. Results: Using an increase of 1.8 mm or more at the bovine PPD site as a cut-off for positive responders, 69% of 16 M. bovis culture-positive warthogs had a positive test result, with 100% of the 18 culture-negative warthogs considered as test negative. When a differential of 1.2 mm or more in skin fold thickness at the bovine PPD compared to the avian PPD site was used as a cut-off for the comparative ITT, 81% of culture-positive warthogs were considered as test positive, with 100% of culture-negative warthogs considered as test negative. Conclusion: The findings in this study suggest that the ITT is a promising tool to use when screening warthogs for M. bovis infection.
Mycobacterium bovis in a free-ranging black rhinoceros, Kruger National Park, South Africa, 2016
(Centers for Disease Control and Prevention, 2017) Miller, Michele Ann; Buss, Peter E.; Van Helden, Paul D.; Parsons, Sven D. C.
In 2016, an emaciated black rhinoceros (Diceros bicornis) was found in Kruger National Park, South Africa. An interferon-γ response was detected against mycobacterial antigens, and lung tissue was positive for Mycobacterium bovis. This case highlights the risk that tuberculosis presents to rhinoceros in M. bovis–endemic areas.
Paratuberculosis in a domestic dog in South Africa
(AOSIS Publishing, 2017) Miller, Michele Ann; Davey, Sewellyn C.; Van Helden, Lesley S.; Kettner, Frank; Weltan, Sandy M.; Last, Rick; Grewar, John D.; Botha, Louise; Van Helden, Paul D.
This case report shows that Mycobacterium avium subsp. paratuberculosis (MAP) infection can cause clinical disease in domestic dogs, and should be considered as a differential diagnosis for gastrointestinal inflammatory conditions. A male dachshund presented with lethargy and pain. Enlarged mesenteric lymph nodes were found on abdominal ultrasound examination. Cytological examination of lymph node aspirates was consistent with granulomatous inflammation, which was culture-confirmed as MAP. Although we were unable to confirm the source of infection, the dog’s history included exposure to sheep in the Western Cape.
A pilot study evaluating the utility of commercially available antibodies for flow cytometric analysis of Panthera species lymphocytes
(BMC (part of Springer Nature), 2018-12-19) Sylvester, Tashnica Taime; Parsons, Sven David Charles; Van Helden, Paul D.; Miller, Michele Ann; Loxton, Andre Gareth
Background: The immune response against tuberculosis in lions is still poorly defined and our understanding is hampered by the lack of lion specific reagents. The process for producing antibodies against a specific antigen is laborious and not available to many research laboratories. As the search for antibody cross-reactivity is an important strategy for immunological studies in veterinary medicine, we have investigated the use of commercially available antibodies to characterize T cell subsets in African lions (Panthera leo). Results: Commercially available antibodies were screened and investigated the influence of two different sample processing methods, as well as the effect of time delay on cell surface marker expression on lion lymphocytes. Using commercially available antibodies, we were able to identify CD4+, CD5+, CD8+, CD14+, CD25+, CD44+ and CD45+ T lymphocytes in samples obtained by density gradient centrifugation as well as red cell lysis of lion whole blood. Two distinct lymphocyte populations, which differed in size and phenotype, were observed in the samples processed by density gradient centrifugation. Conclusion: Commercially available antibodies are able to differentiate between T lymphocyte subsets including immune effector cells in African lion whole blood, and possibly give insight into unique specie phenotypes.
Use of butorphanol and diprenorphine to counter respiratory impairment in the immobilised white rhinoceros (Ceratotherium simum)
(AOSIS, 2018) Meyer, Leith C. R.; Fuller, Andrea; Hofmeyr, Markus; Buss, Peter E.; Miller, Michele Ann; Haw, Anna
Opioid-induced immobilisation results in severe respiratory impairment in the white rhinoceros. It has therefore been attempted in the field to reverse this impairment with the use of opioid agonist-antagonists, such as nalorphine, nalbuphine, butorphanol and diprenorphine; however, the efficacy of some of these treatments has yet to be determined. The efficacy of butorphanol, either alone or in combination with diprenorphine both with and without oxygen insufflation, in alleviating opioid-induced respiratory impairment was evaluated. The study was performed in two parts: a boma trial and a field trial. Rhinoceroses were immobilised specifically for the study, according to a strict protocol to minimise confounding variables. A two-way analysis of variance was used to compare the physiological responses of the rhinoceroses to the different treatments and their effects over time. The intravenous administration of butorphanol (at 3.3 mg per mg etorphine) plus diprenorphine (at 0.4 mg per mg etorphine) did not offer any advantage over butorphanol (at 15 mg per mg etorphine) alone with regard to improving PaO2, PaCO2 and respiratory rates in etorphine-immobilised white rhinoceroses. Both butorphanol + diprenorphine + oxygen and butorphanol + oxygen, at the doses used, significantly improved the etorphine-induced hypoxaemia in both boma- and field-immobilised white rhinoceroses. Clinically acceptable oxygenation in field-immobilised white rhinoceroses can be achieved by using either treatment regimen, provided that it is combined with oxygen insufflation.
The VetMAX™ M. tuberculosis complex PCR kit detects MTBC DNA in antemortem and postmortem samples from white rhinoceros (Ceratotherium simum), African elephants (Loxodonta africana) and African buffaloes (Syncerus caffer)
(BMC (part of Springer Nature), 2020) Goosen, Wynand J.; Kerr, Tanya J.; Kleynhans, Leanie; Buss, Peter E.; Cooper, David; Warren, Robin M.; Van Helden, Paul D.; Schroder, Bjorn; Parsons, Sven D. C.; Miller, Michele Ann
Background: Bovine tuberculosis and tuberculosis are chronic infectious diseases caused by the Mycobacterium tuberculosis complex members, Mycobacterium bovis and Mycobacterium tuberculosis, respectively. Infection with M. bovis and M. tuberculosis have significant implications for wildlife species management, public health, veterinary disease control, and conservation endeavours. Results: Here we describe the first use of the VetMAX™ Mycobacterium tuberculosis complex (MTBC) DNA quantitative real-time polymerase chain reaction (qPCR) detection kit for African wildlife samples. DNA was extracted from tissues harvested from 48 African buffaloes and MTBC DNA was detected (test-positive) in all 26 M. bovis culture-confirmed animals with an additional 12 PCR-positive results in culture-negative buffaloes (originating from an exposed population). Of six MTBC-infected African rhinoceros tested, MTBC DNA was detected in antemortem and postmortem samples from five animals. The PCR was also able to detect MTBC DNA in samples from two African elephants confirmed to have M. bovis and M. tuberculosis infections (one each). Culture-confirmed uninfected rhinoceros and elephants’ samples tested negative in the PCR assay. Conclusions: These results suggest this new detection kit is a sensitive screening test for the detection of MTBCinfected African buffaloes, African elephants and white rhinoceros.

Browsing by Author "Miller, Michele Ann"

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