Bovine tuberculosis in African buffalo (Syncerus caffer): Progression of pathology during infection.

BackgroundBovine tuberculosis (BTB) is a zoonotic disease of global importance endemic in African buffalo (Syncerus caffer) in sub-Saharan Africa. Zoonotic tuberculosis is a disease of global importance, accounting for over 12,000 deaths annually. Cattle affected with BTB have been proposed as a model for the study of human tuberculosis, more closely resembling the localization and progression of lesions in controlled studies than murine models. If disease in African buffalo progresses similarly to experimentally infected cattle, they may serve as a model, both for human tuberculosis and cattle BTB, in a natural environment.Methodology/Principal findingsWe utilized a herd of African buffalo that were captured, fitted with radio collars, and tested for BTB twice annually during a 4-year-cohort study. At the end of the project, BTB positive buffalo were culled, and necropsies performed. Here we describe the pathologic progression of BTB over time in African buffalo, utilizing gross and histological methods. We found that BTB in buffalo follows a pattern of infection like that seen in experimental studies of cattle. BTB localizes to the lymph nodes of the respiratory tract first, beginning with the retropharyngeal and tracheobronchial lymph nodes, gradually increasing in lymph nodes affected over time. At 36 months, rate of spread to additional lymph nodes sharply increases. The lung lesions follow a similar pattern, progressing slowly, then accelerating their progression at 36 months post infection. Lastly, a genetic marker that correlated to risk of M. bovis infection in previous studies was marginally associated with BTB progression. Buffalo with at least one risk allele at this locus tended to progress faster, with more lung necrosis.Conclusions/SignificanceThe progression of disease in the African buffalo mirrors the progression found in experimental cattle models, offering insight into BTB and the interaction with its host in the context of naturally varying environments, host, and pathogen populations.

During a five year period (2000–2004), the incidence of bovine and human tuberculosis in cattle and other animals from six Central European countries was evaluated: Croatia (HRV), the Czech Republic (CZE), Hungary (HUN), Poland (POL), Slovakia (SVK), and Slovenia (SVN). These countries, lying between the Baltic and the Adriatic seas, cover an area of 610 402 km<sup>2</sup> and had more than 68 million inhabitants and 9 330 264 cattle in 2003. Successful national control programmes against bovine tuberculosis in cattle were carried out up until 1980: HRV (1953–1966), CZE (1959–1968), HUN (1962–1980), POL (1959–1975) SVK (1959–1968), and SVN (1962–1973). During the entire monitored period skin testing with bovine tuberculin in all cattle older than two years was carried out regularly either once a year or every second year. Five of these countries (CZE, HUN, POL, SVK, and SVN) joined the EC on May 1<sup>st</sup>, 2004. CZE and SVK were officially declared free of bovine tuberculosis in cattle on March 31<sup>st</sup>, 2004 (Commission Decision No. 2004/320/EC) and March 4<sup>th</sup>, 2005 (Commission Decision No. 2005/179/EC), respectively. Bovine tuberculosis was diagnosed in a total of 188 cattle herds in the study area: 145 (77.1%) outbreaks in small herds (< 10 cows) and 43 (22.9%) outbreaks in large herds (≥ 10 cows). The last cases of bovine tuberculosis in cattle in SVK and in the CZE were diagnosed in 1993 and 1995, respectively. During the monitored period, bovine tuberculosis was diagnosed in animal species other than cattle found in zoological gardens: in two Bactrian camels (Camelus ferus) in the CZK, in one Siberian tiger (Panthera tigris f. altaica) in HUN, in one bison (Bison bison) and one eland (Taurotragus oryx) in POL, and in one dromedary camel (Camelus dromedarius) and two bison in SVN. In wild animals, bovine tuberculosis was diagnosed in wild boar (Sus scrofa) in HUN (n = 14) and HRV (n = 1), in six red deer (Cervus elaphus) in HUN, in 14 European bison (Bison bonasus f. bonasus) and two roe deer (Capreolus capreolus f. capreolus) in POL. Infections caused by Mycobacterium tuberculosis were also diagnosed in four cattle and two pigs in POL, in one cattle in SVN, in one dog (Canis lupus f. familiaris) in the CZE and in one dog in HUN. M. africanum was diagnosed in one hyrax (Procaria habessinica) in a zoological garden in HRV.

International audience

Sadly, despite a previous warning of a cattle tuberculosis (TB) crisis (Hancox 1998a,b), there has been a steady worsening of the situation with a very real risk to public health. Bovine TB is now back to 1960s levels in Britain, from a low point in the mid‐1970s of 89 herds and 600 cases to 872 new herds and 7000 cases in 1999. TB has spread from tiny south‐west ‘hot spots’ to an area from Cornwall up to Cheshire/Derbyshire (distribution maps in Krebs 1997). Irish incidence has gone back to 1970s levels with over 45 000 cases last year. Over the last 30 years attention has focused to such an extent on badgers (Meles meles L.) as the ‘main source’ of further herd outbreaks, that amidst the confused debate over this ‘highly complex and emotive issue’, it is quite extraordinary that the importance of cattle‐to‐cattle transmission is seriously questioned (Griffin and Dolan 1995; O'Reilly and Daborn 1995; Gardner 1999; Anonymous 2000; Bourne 2000; Morrison et al. 2000), and this despite a century's experience of cattle TB schemes in over a hundred countries to the contrary! Out of five main schemes the widespread success of ‘area eradication’ rests on a robust scientific base as the most cost‐effective and sustainable means of minimizing or preventing transmission within the cattle population. But whereas early on, most test reactors are lesioned and infectious, late on most ‘reactors’ do not have ‘tubercle’ lesions and are not infectious because they do not have TB, hence the confusion (Francis 1947).

Although the first diagnosis of tuberculosis in wildlife in Africa was made during the mid-1920s, it was only during the mid to late 1900s that the importance of the disease in wildlife became evident following its diagnosis in African buffaloes (Syncerus caffer) and Kafue lechwe (Kobus leche kafuensis) that are now both known to be maintenance hosts of the disease. In addition to these two species, greater kudus (Tragelaphus strepsiceros), warthogs (Phacochoerus aethiopicus), and lions (Panthera leo) appear to possibly be able to sustain the infection. This turn of events has serious implications not only for wildlife itself but also for the control and eradication of bovine tuberculosis (BTB) in cattle and other livestock. It is now known to be notoriously difficult to control BTB in countries in which wildlife maintenance hosts occur, and this situation will add to the difficulty of dealing with the disease on a continent where limited resources restrict the extent to which this serious zoonotic disease can be dealt with, both in livestock and in humans. The role of wildlife in the epidemiology of BTB in cattle, and in humans, is unknown and will have to be assessed should Africa as a continent wish to participate in the international drive to eliminate tuberculosis in humans during the course of the next number of decades. This chapter provides some information about bovine tuberculosis in wildlife in Africa with emphasis on those wildlife species that have been identified as maintenance hosts.

Distribution of Lesions in Red and Fallow Deer Naturally Infected with Mycobacterium bovis

Tuberculosis pathology was studied on 19 African buffalo (Syncerus caffer) from a herd in the Hluhluwe-iMfolozi Park in South Africa. The animals tested positive with the comparative intradermal tuberculin test and were euthanized during a test-and-cull operation to decrease prevalence of bovine tuberculosis (bTB) in the park. The lymph nodes and lungs were examined grossly for presence of tuberculous lesions, which were scored on a 0-5 scale for macroscopic changes. The gross lesions were examined histologically and classified into grade I, II, III, or IV according to a grading system used for bTB lesions in domestic cattle. Macroscopic lesions were limited to the retropharyngeal, bronchial, and mediastinal lymph nodes and the lungs. The most frequently affected lymph nodes were the bronchial (in 16 animals) and mediastinal (in 11 animals). All four grades of microscopic lesions were observed, grade II lesions were the most frequent. Mycobacterium bovis was detected by PCR in 8 out of 19 animals, and acid-fast bacilli were seen in 7 out of 19 animals, together both techniques identified mycobacteria in 5 out of 19 animals. Lesions were paucibacillary, as acid-fast bacilli were only rarely observed. The absence of lesions in the mesenteric lymph nodes and the high frequency of lesions in respiratory tract associated lymph nodes suggest that the main route of M. bovis infection in African buffalo is by inhalation.

Toll-like receptor (TLR) diversity influences mycobacterial growth in African buffalo

The European settlers with the importation of infected cattle, introduced bovine tuberculosis (BTB) into South Africa. The first case of BTB in cattle was detected in 1880 and in wildlife during the 1920s. As early as 1906, legislation was promulgated to control and attempt to eradicate BTB from the country, but without success. Intensive application of the test-and-slaughter policy to control BTB in the late 1960s reduced the prevalence in commercial dairy herds to 0.04%. Following the democratic elections in the country in 1994, because of the fragmentation of services caused by the provincialization of veterinary services, and the lack of funding and human resources, the prevalence increased substantially. Currently, bovine tuberculosis (BTB) is spread throughout the country, and it also occurs in more than 20 wildlife species of which African buffaloes (Syncerus caffer), and perhaps greater kudus (Tragelaphus strepsiceros), are maintenance hosts. This situation creates major challenges for the regulatory authorities to control and attempt to eradicate the disease, particularly because of the presence of maintenance hosts other than cattle throughout the country, which are sustained by the rapidly expanding game ranching industry.

BackgroundThe aim of the current study was to assess the prevalence of bovine tuberculosis (BTB) in cattle, goats, and camels, and its zoonotic potential within the traditional livestock raising communities in four regions of Eritrea. The Single Intradermal Comparative Tuberculin Test (SICTT) as indicator of M. bovis infection was conducted on 1077 cattle, 876 goats, and 195 camels. To elucidate possible risk factors for BTB transmission between animals and its potential zoonotic implication, questionnaire based face-to-face interviews were conducted in households of which 232 raised cattle, 128 goats, and 29 camels.ResultsThe results of the SCITT were interpreted using the OIE standard (> 4 mm cut-off) for positive responses. In cattle, individual animal (n = 1077) and herd (n = 413) prevalences were 1.2% (n = 13) [Confidence Interval (CI) 95% CI, 1.0–1.3%] and 3.2% (n = 13) (95% CI, 3.0–3.4%), respectively. In goats (n = 876), none of the animals was positive. In camels, individual animal (n = 195) and herd (n = 70), BTB prevalences were 1.5% (n = 3) (95% CI,1.4–1.6%) and 2.9(n = 2) (95% CI, 0.9–4.6%), respectively. Overall, male animals were more at risk (OR = 2.6; 95% CI:1.0–8.7) when compared to females. Sharing of water points, introduction of new animals into herds and migration of animals over large distances were common events that may contribute to intra and inter-species transmission of BTB. Consumption of raw milk, lack of BTB transmission awareness, and low levels of education were common in the farming communities.ConclusionThe current study highlighted a low prevalence of M. bovis in cattle, goats and camels in extensive traditional livestock in Eritrea. Despite this, the spatial distribution of affected animals across most of the sampled regions and consumption of unpasteurized milk warrants surveillance, cautious and timely control measures for the disease.

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.

Risk factors of tuberculosis in human and its association with cattle TB in Nepal: A one health approach

Field application of immunoassays for the detection of Mycobacterium bovis infection in the African buffalo (Syncerus caffer)

A survey on Mycobacterium bovis and M. tuberculosis in humans has been performed in four Central European countries (Croatia, the Czech Republic, Slovak Republic and Slovenia) during the years 1990 to 1999. These countries cover an area of 204 688 km<sup>2</sup> with 22 135 million population. During the period, new cases of tuberculosis were bacteriologically diagnosed in 47 516 patients. M. tuberculosis was detected in 47 461 (99.88%) cases, whereas M. bovis was found only in 55 (0.12%) patients. The rate of infection due to M. bovis in humans did not exceed 0.29% in the study countries. The annual incidence of bacteriological confirmed M. bovis cases did not exceed 0.1 per 100 000 inhabitants. In the Czech Republic out of 44 tuberculosis patients due to M. bovis, 32 (72.7%) were older than 61 years and originated from rural areas, where they lived during childhood and worked in agricultural occupations. These patients may have suffered a reactivation of persistent (long-standing) M. bovis infection as they got older. Bovine tuberculosis in cattle was eliminated from these countries during the second half of the 1960s (Croatia in 1966, Czech Republic and Slovak Republic – former Czechoslovakia in 1968, Slovenia in 1973) and the incidence of outbreaks of bovine tuberculosis in cattle were very low, thus the disease in humans was unexpected.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. bovis), is a globally prevalent zoonotic infectious disease. World Organization for Animal Health (WOAH) estimates indicate that up to 10% of the total human TB cases in developing countries are attributed to M. bovis. Pakistan ranks 4th in global milk production with a livestock population of over 212 million animals. Over 8 million families are involved in raising these animals as a means of livelihood. To date, there is an absence of national-level data on the prevalence of bTB and an effective control program is still lacking. The multifaceted impacts and substantial economic losses render addressing bTB a daunting, but highly important challenge. In this review, we summarise all the freely available literature on M. bovis infection from Pakistan using Google scholar and PubMed databases. A total of 40 animal studies were identified using search terms: “bovine tuberculosis in Pakistan, bTB, Pakistan, Mycobacterium bovis in Pakistan, M. bovis in Pakistan”; while seven human studies were identified using the terms: zoonotic tuberculosis in Pakistan’, ‘M. bovis in humans Pakistan’, ‘zTB in TB patients in Pakistan”. We have summarized all these studies to identify critical risk factors involved in transmission of bTB among animals and humans. Despite lack of comprehensive and geographically representative studies, the literature suggests a varying prevalence of bTB in animals, ranging from as low as 2% to as high as 19%. Regarding zTB prevalence in humans, estimates range from 1.5% to 13% in high-risk group of farm and abattoir workers, with notably higher percentages in extra-pulmonary TB cases. The review also addresses the challenges that Pakistan faces in formulating an effective policy for the control and eradication of bTB. We conclude with one-health based recommendations as a way forward for controlling TB caused by M. bovis in cattle and humans.