No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Tuberculosis in Nonhuman Primates with and Emphasis on Mycobacterium Bovis
Abstract
Early Investigation and Natural HistoryTuberculosis: Clinical SignsPathogenesisPathologyHistological NarrativeDiagnostic Testing and ConsiderationsPrevention and ControlAcknowledgment
... Outras formas de transmissão geralmente ocorrem através de brigas (mordidas), contato com fômites contaminados e através de procedimentos médicos com materiais contaminados (KING, 1993;KAUFMANN;ANDERSON 14 , 1978 gordoneae, pode resultar em reação falso-positiva (SOAVE et al., 1981;DUKELOW;PIERCE, 1987;MALAGA et al., 2004;FROST, 2006). (SUPPLY et al., 1997;SUPPLY et al., 2000;BARNES;CAVE, 2003 , 1978;KING, 1993;CAPUANO et al., 2003;ISAZA, 2003;KANEENE;THOEN, 2004;FLYNN, 2006;FROST, 2006 horas (KING, 1993;ISAZA, 2003;FROST, 2006 (KING, 1993;FROST, 2006). ...
... Outras formas de transmissão geralmente ocorrem através de brigas (mordidas), contato com fômites contaminados e através de procedimentos médicos com materiais contaminados (KING, 1993;KAUFMANN;ANDERSON 14 , 1978 gordoneae, pode resultar em reação falso-positiva (SOAVE et al., 1981;DUKELOW;PIERCE, 1987;MALAGA et al., 2004;FROST, 2006). (SUPPLY et al., 1997;SUPPLY et al., 2000;BARNES;CAVE, 2003 , 1978;KING, 1993;CAPUANO et al., 2003;ISAZA, 2003;KANEENE;THOEN, 2004;FLYNN, 2006;FROST, 2006 horas (KING, 1993;ISAZA, 2003;FROST, 2006 (KING, 1993;FROST, 2006). toda a equipe envolvida no processo (WARD et al., 1985;WOLF et al., 1988;JOHNSON-DELANEY, 1994;BUSHMITZ et al., 2009 (WARD et al., 1985;WOLF et al., 1988;JOHNSON-DELANEY, 1994;BUSHMITZ et al., 2009 • as paredes, tetos e chão devem ser resistentes à água para facilitar a higiene e a desinfecção, ...
... Outras formas de transmissão geralmente ocorrem através de brigas (mordidas), contato com fômites contaminados e através de procedimentos médicos com materiais contaminados (KING, 1993;KAUFMANN;ANDERSON 14 , 1978 gordoneae, pode resultar em reação falso-positiva (SOAVE et al., 1981;DUKELOW;PIERCE, 1987;MALAGA et al., 2004;FROST, 2006). (SUPPLY et al., 1997;SUPPLY et al., 2000;BARNES;CAVE, 2003 , 1978;KING, 1993;CAPUANO et al., 2003;ISAZA, 2003;KANEENE;THOEN, 2004;FLYNN, 2006;FROST, 2006 horas (KING, 1993;ISAZA, 2003;FROST, 2006 (KING, 1993;FROST, 2006). toda a equipe envolvida no processo (WARD et al., 1985;WOLF et al., 1988;JOHNSON-DELANEY, 1994;BUSHMITZ et al., 2009 (WARD et al., 1985;WOLF et al., 1988;JOHNSON-DELANEY, 1994;BUSHMITZ et al., 2009 • as paredes, tetos e chão devem ser resistentes à água para facilitar a higiene e a desinfecção, ...
A Tuberculose é um dos maiores problemas sanitários dos animais selvagens mantidos em cativeiro para os mais variados propósitos. Grande parte das ocorrências envolve a transmissão zoonótica e os primatas não humanos são os animais mais frequentemente afetados. Em função das complexidades para o seu controle, determina grandes perdas econômicas e a estigmatização da instituição que a reporta. Enquanto nos países da América do Norte e Europa é tratada como prioridade, havendo estratégias definidas por legislação, no Brasil, existe quase completa omissão em relação à doença, o que resulta em individualismo no trato do problema por parte das instituições mantenedoras de animais cativos. Assim, este livro trata desse assunto sob a ótica da medicina veterinária preventiva, com natural ênfase nas populações animais. Aborda desde aspectos históricos até sistemas de vigilância, passando por detalhes da etiologia, epidemiologia, patogenia, sinais clínicos, diagnóstico e legislação brasileira, visando chamar atenção para o tema e inspirar iniciativas para o bom encaminhamento da questão no nosso meio.
... In comparison, there is less knowledge about Mycobacterium bovis infection in Old World monkeys. Mycobacterium bovis infection and disease, as well as infection with other MTBC, such as Mycobacterium orygis and Mycobacterium caprae, has been sporadically reported in captive non-human primates (16)(17)(18)(19)(20)(21). However, studies of M. bovis infection in free-ranging African primates are more limited, although they have been focused on M. bovis endemic areas. ...
Animal tuberculosis (TB) has been reported in several wildlife species in the Greater Kruger Conservation Area (GKCA), South Africa. This report describes the discovery of clinical tuberculosis, caused by Mycobacterium bovis (M. bovis), in free-ranging vervet monkeys (Chlorocebus pygerythrus). The “One Health” concept is especially relevant to TB since this is a multi-host disease with zoonotic potential and is endemic in GKCA. Vervet monkeys have become habituated to humans in tourist areas and may be a source of infection through close contact. Indirect transmission of M. bovis through environmental sources has also been suspected to present a risk of spread between host species. Clinically diseased monkeys present in two tourist areas in the GKCA, that died (n = 1) or were euthanized (n = 5), were submitted for diagnostic necropsies. The presence of pathological lesions, Ziehl-Neelsen-stained impression smears, Xpert® MTB/RIF Ultra (GXU) assay, mycobacterial culture and speciation by genomic regions of difference PCR, were used to confirm the diagnosis of M. bovis infection in these monkeys. The finding of multiple cases necessitates further investigation of TB in monkey troops living within the GKCA tourist areas to determine the source of infection and assess the risk of transmission to other animals and humans.
... Tuberculosis (TB) is an emerging zoonotic disease of captive and free-ranging wildlife species with severe consequences in biodiversity and species conservation. Tuberculosis bacteria has a wide wild life host range which includes Elephants [1][2][3], Sloth Bears [4,5], Arabian Oryx [6], White tailed Deer [7], Reindeer [8], European Badgers [7,9,10], Cervids [8], Rhinoceros [11], Lion [12], Badgers [13] and non-humane primates [2,14]. So far 60 different wild mammal species were proven to be infected with TB [15,16]. ...
Tuberculosis is a significant problem globally for domestic animals as well as captive and free ranging wild life. Rapid point of care (POC) serology kits are well suited for the diagnosis of TB in wild animals. However, wild animals are invariably exposed to environmental non-pathogenic mycobacterium species with the development of cross reacting antibodies. In the present study, POC TB diagnosis kit was developed using a combination of pathogenic Mycobacteria specific recombinant antigens and purified protein derivatives of pathogenic and non-pathogenic Mycobacteria. To benchmark the TB antibody detection kit, particularly in respect to specificity which could not be determined in wildlife due to the lack of samples from confirmed uninfected animals, we first tested well-characterized sera from 100 M. bovis infected and 100 uninfected cattle. Then we investigated the kit’s performance using sera samples from wildlife, namely Sloth Bears (n = 74), Elephants (n = 9), Cervidae (n = 14), Felidae (n = 21), Cape buffalo (n = 2), Wild bear (n = 1) and Wild dog (n = 1).In cattle, a sensitivity of 81% and a specificity of 90% were obtained. The diagnostic sensitivity of the kit was 94% when the kit was tested using known TB positive sloth bear sera samples. 47.4% of the in-contact sloth bears turned seropositive using the rapid POC TB diagnostic kit. Seropositivity in other wild animals was 25% when the sera samples were tested using the kit. A point of care TB sero-diagnostic kit with the combination of proteins was developed and the kit was validated using the sera samples of wild animals.
Ten South American sea lions (Otaria flavescens) were presented for clinical evaluation and diagnosis of tuberculosis following known exposure to Mycobacterium pinnipedii. CT was used to determine whether foci of calcification in mediastinal lymph nodes, typically associated with pinniped tuberculosis, could be detected and whether CT was a useful diagnostic modality, in conjunction with other tests, for the diagnosis of tuberculosis in this species. Blood was collected from the caudal gluteal vein of each animal for serological testing using commercially available serological tests (ElephantTB STAT-PAK and DPP Vet; Chembio Diagnostic Systems) and a multiantigen print immunoassay (MAPIA), carried out at Chembio to verify the in-house kits. In four of nine animals that underwent CT scanning, lesions consistent with pinniped tuberculosis were apparent and these were confirmed at subsequent postmortem examination. The five remaining animals did not show any abnormalities on CT, with three being negative on serological tests, which were considered to be normal and potentially used as reference images for healthy sea lions. One animal could not be CT scanned due to its large size and weight (510 kg).
Tuberculosis continues to be an important disease both in humans and animals. It causes morbidity, mortality and economic loss worldwide. The occurrence of Mycobacterium bovis disease in humans, domesticated and wild animals confirms the relevance of this zoonosis. M. bovis in humans continues to be reported in industrialised countries and in immigrants from regions of the world where tuberculosis in cattle is endemic. The real incidence of M. bovis in humans in developing countries continues to be roughly under-estimated due to the scarcity of appropriate laboratory facilities to isolate and to differentiate M. bovis strains. In Latin America, less than 1% of tuberculosis cases are reported as being due to M. bovis. However, the economic relevance that meat and dairy industries play in these countries stimulates the promotion of bovine tuberculosis eradication programmes. Human-to-human airborne transmission of M. bovis does occur and it may be important where human immunodeficiency virus (HIV) infection in humans is prevalent, M. bovis infection in cattle is enzootic and pasteurisation of dairy products is not routinely practised. Eradication of M. bovis in cattle and pasteurisation of dairy products are the cornerstones of prevention of human disease. Measures should be developed to identify and control M. bovis infection in wild animals as these may be important reservoirs of infection for domesticated food-producing animals. There is a need for medical and veterinary professionals to cooperate on disease outbreaks. The information presented herein strongly supports the 'One World/One Health/One Medicine' concept.
The infection of a variety of free-ranging wildlife species with Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), can cause problems for biodiversity and species conservation. In some notable cases, particular species act as a reservoir of infection that can spill over into domestic livestock with economic and zoonotic consequences. Immunological methods for the detection of TB infection in wildlife are important for diagnostic and research purposes, especially where post-mortem examination is neither feasible nor desirable. In this review, the approaches taken to the immunological study of TB in wildlife species are summarized, with particular emphasis on their suitability for different applications and their applicability to different species. Different approaches to improving diagnostic sensitivity are discussed together with factors that can confound the use of tests in certain situations. Caution in the interpretation of test results for TB in wildlife is encouraged, especially where it has not been possible to confirm the accuracy of the test.
Although non-human primates (NHP) account for less than a fraction of one percent of all of the animals used for biomedical research, their many similarities to humans make them vital, and presently irreplaceable, models for humans for certain types of research (Hau et al., 2000). The most common areas of research in which NHP are used include microbiology (including HIV/AIDS), neuroscience and biochemistry/ chemistry. Several of the Old World monkeys (Chlorocebus aethiops, Macaca mulatta, M. fascicularis and Papio spp.) are the most commonly used species for research (Carlsson et al., 2004). Based on all articles published in 2001, it has recently been estimated that the global number of NHP used in research, including those participating in more than one protocol, is in the vicinity of 100,000-200,000 animals annually (Carlsson et al., 2004). The authors of the present paper were invited to give evidence to the joint Academy of Medical Sciences/Medical Research Council/Royal Society/Wellcome Trust study into the use of non-human primates in research, and this article is therefore addressed to the joint committee.
The gross findings in nonhuman primates with tuberculosis can vary from no detectable lesions to widely disseminated, 1.0–10.0mm, yellow-white, focal to confluent granulomas affecting all major organs (Fig. 153). On cut-section, the granulomas contain a central core of yellow-white caseous material. Organs most often affected include the lungs, hilar lymph nodes, spleen, liver, kidney, intestine, and mesenteric nodes, but any organ may be involved. Large granulomas in the lung may be cavitary as the result of expulsion of the caseous exudate into adjacent airways. Adhesions may also occur between the affected portions of the lung and the adjacent parietal pleura. Tuberculous lesions involving the vertebra and adjacent spinal cord, termed “Potts’ disease” in humans, have also been described in nonhuman primates (Innes 1963; Lapin and Yakovleva 1963; Martin et al. 1968; Fox et al. 1974; Tryphonas and Wong 1982).
This chapter presents a discussion on some bacterial and mycotic diseases of nonhuman primates. Bacteria are presented in the general order of gram-positive, gram-negative, and acid-fast organisms. Some of the genera of bacteria discussed in the chapter include Streptococcus, Staphylococcus, Corynebacterium, Listeria, Erysipelothrix, Clostridium, Neisseria, Branhamella, Escherichia, Salmonella, Shigella, Yersinia, Klebsiella, Bordetella, Pasteurella, Francisella, Pseudomonas, Aeromonas, and Campylobacter. Dermatophytosis or ringworm in nonhuman primates is caused by organisms of the genera Microsporum and Trichophyton. This condition occurs rarely in nonhuman primates. Dermatophytes invade the horny layer of the skin and hair and produce a mild inflammatory response and hyperkeratosis. Microsporum canis, Microsporum gypseum, and Trichophyton mentagrophytes produce arthrospores arranged on the outside of the hair shaft. Dermatophytes invade the anagen hairs and grow down the follicle toward the layer of mitotic activity. The chapter concludes with a discussion of several systemic yeast infections and systemic hyphal infections that are diagnosed in nonhuman primates.
VirulenceHost ResponseGranulomatous Lesion DevelopmentReferences
IntroductionBovine Tuberculosis in CattleTuberculous Lesions in Cattle Caused By Other Causal Agents than Mycobacterium Bovis or Mycobacterium CapraeCurrent Risk Factors for the Spread of Bovine TuberculosisBovine Tuberculosis and Tuberculous Lesions Caused By Other Causal Agents in Domestic PigsBovine Tuberculosis in Animal Species Other than Cattle and Domestic PigMolecular Epidemiology of Bovine TuberculosisBovine Tuberculosis in the Human PopulationInfection Caused By M. Tuberculosis in Domestic and Wild AnimalsConclusions
Despite the availability of effective control measures, simian tuberculosis continues to be a major colony management problem. In 1972, 909 cases of simian tuberculosis were reported to the Center for Disease Control. Most of the cases (838) were in rhesus monkeys (Macaca mulatta). The attack rate was higher for animals conditioned by commercial importers prior to sale (6.6%) than for animals received shortly after importation without conditioning (1.2%) . Failure to apply control measures effectively and consistently both in trade channels and at the user level is a significant factor in peptuation of the problem.
An enzyme immunoassay (EIA) was developed for detecting mycobacterial antibodies in the sera of 22 Macaca fascicularis following a natural outbreak of tuberculosis. EIAs were conducted using four antigens (lysozyme, triton, or deoxycholate extracts of Mycobacterium tuberculosis or a purified protein derivative) and two conjugates (protein A or antihuman). Mycobacterial antibodies were detected in two of two culture-positive monkeys, in nine of ten tuberculin test-suspect monkeys (culture-negative), and in five of ten tuberculin test-negative monkeys (culture-negative). Results indicate EIA may be of practical value in detecting monkeys exposed to M. tuberculosis.
Occurrence of tuberculosis caused by Mycobacterium bovis in a colony of rhesus monkeys allowed evaluation of a modern multidrug therapeutic regimen. Fifteen tuberculin positive rhesus monkeys with disseminated tuberculosis were evaluated for extent of disease by radiographic techniques, physical examination and laparotomy prior to treatment. Monkeys were divided into treatment groups of 3, 6 and 12 months duration and were treated once daily with isoniazid, rifampin and ethambutol. All animals survived their treatment course, had marked clinical improvement and rapid resolution of radiographically demonstrable lesions. Lesion regression evaluated by necropsy and histopathology correlated positively with length of treatment interval. Mycobacterium bovis was not isolated from any animal following treatment. Multidrug chemotherapy of tuberculosis was considered successful and practical in rhesus monkeys at the 12 month treatment interval. Chemotherapy may provide a reasonable alternative to destruction of valuable animals infected with tuberculosis.
Tuberculous spondylitis in an adult male rhesus monkey (Macaca mulatta) is described. Paraplegia with marked kyphosis of the upper lumbar spine characterized the clinical signs. Tuberculin skin tests were positive only after the onset of clinical signs. Radiographic and histologic interpretation of the vertebral lesions are discussed.
An enzyme-linked immunosorbent assay (ELISA) was developed, using protein A labeled with horseradish peroxidase for detecting antibodies in tuberculous exotic mammals (llamas, rhinoceroses, elephants). The modified ELISA provides a rapid procedure for screening several animal species simultaneously for tuberculosis without the production of specific anti-species conjugates. Heat-killed cells of Mycobacterium bovis and M avium and purifed protein-derivative tuberculin of M bovis were used as antigens for ELISA.
A nonhuman primate model of tuberculosis that closely resembles human disease is urgently needed. We have evaluated the Philippine cynomolgus monkey, Macaca fasicularis, as a model of TB. Cynomolgus monkeys challenged intratracheally with extremely high doses of Mycobacterium tuberculosis (10(5) or 10(4) CFU) developed an acute, rapidly progressive, highly fatal multilobar pneumonia. However, monkeys challenged with moderate or low doses of M. tuberculosis (</=10(3) CFU) developed a chronic, slowly progressive, localized form of pulmonary TB, akin to the disease in humans, that was frequently accompanied by such clinical syndromes as ocular tuberculosis, meningitis and tuberculous spondylitis. A significant proportion of monkeys challenged with 10(2) or 10(1) CFU contained the infection in a subclinical state. The Philippine cynomolgus monkey model is an excellent model of chronic TB and provides an opportunity to study subclinical and potentially latent disease in an animal model.
During the fall of 2001, a tuberculosis outbreak caused by Mycobacterium bovis occurred in a conditioned colony of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques at Stanford University School of Medicine. During this outbreak, we evaluated the diagnostic performance of a new in vitro tuberculosis screening test (PRIMAGAM). The PRIMAGAM test measures the interferon-gamma (IFNgamma) response to purified protein derivatives (PPDs) of M. bovis and M. avium. On the basis of the results of the last test administered before necropsy, the PRIMAGAM test had good sensitivity (68%) and excellent specificity (97%), compared with the disease status, as determined by the presence or absence of gross and/or histologic lesions indicative of tuberculosis. By contrast, sensitivity and specificity of the tuberculin skin test (TST) was 84 and 87%, respectively. Both tests suffered from intermittent positive and negative reactions on repeat testing. Overall, however, there was no significant difference (P = 0.09, McNemar's chi2-test) and moderate agreement (kappa = 0.52) between these two tests. Lastly, the IFNgamma response to bovine PPD was significantly lower in infected cynomolgus macaques. Moreover, each test failed to detect tuberculosis in three cynomolgus macaques. Fortunately, they were different animals; therefore, we recommend the parallel use of the TST and PRIMAGAM test for maximal overall sensitivity in a tuberculosis screening program, especially for cynomolgus macaques.
We describe a tuberculosis outbreak caused by Mycobacterium bovis in a conditioned colony of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques. Animals in five rooms were exposed, but most (16/27) infections were confined to the room that housed a mixed population of cynomolgus and rhesus macaques. In this room, rhesus (8/8) and cynomolgus (10/11) macaques naturally exposed to M. bovis were infected at nearly identical rates (Fisher exact test, 2-tailed P = 1). The clinical signs of disease and pathologic lesions in infected macaques, however, were moderately different between the two species. Rhesus macaques were more likely (5/8) to exhibit clinical signs of persistent coughing and inappetance, and had more severe pulmonary lesions. By contrast, clinical signs of disease were seen in only 1 of 19 cynomolgus macaques, and overall, the pulmonary lesions were often focal and less severe, although some still had severe involvement of the lungs similar to that seen in rhesus macaques. These differences should be taken into consideration when developing or evaluating a tuberculosis-screening program. On the basis of observations made during this outbreak, we recommend that alternative screening methods such as the PRIMAGAM test and the ESAT-6 ELISA, be incorporated into the screening program to aid in the identification of infected animals.
Tuberculosis is a term that encompasses various diseases caused by bacteria of the Mycobacterium tuberculosis complex, including M tuberculosis, M bovis, M africanum, and other mycobacterial species. Whereas M tuberculosis infection is largely spread from human to human, M bovis infection has been identified as a zoonotic disease with most cases of human infection attributable to animal sources. The mycobacteria other than tuberculosis complex (MOTT), which includes M avium subsp avium and M avium subsp intracellulare isolated from animals, has been isolated from immune-compromised humans (ie, those with human immunodeficiency virus [HIV] infection), but seldom from immunocompetent humans. Recently, there has been increased interest among public health officials in drug-resistant strains of M tuberculosis, M bovis, and M avium because several have been isolated from HIV-infected and nonimmuno-compromised humans.
Tuberculosis: Pathogenesis, Protection and Control
- C. O. Thoen
Mycobacterial Infections in Zoo Animals
- R. M. McLaughlin
- G. E. Marrs
Gamma interferon enzyme immunoassays and their use in the investigation of tuberculosis in a western lowland gorilla
- H. McCracken