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Epidemiol. Inifect. (1992), 109, 23-33 Printed in Great Britain
Mycobacterium bovis in England and Wales: past, present and future R. M. HARDIE AND J. M. WATSON Respiratory Diseases Section, PHLS Communicable Disease Surveillance Centre, 61, Colindale Avenue, London NIW9 5EQ (Accepted 30 March 1990) SITMMARY
This report reviews the literature concerning tuberculosis resulting from infection with liycobacterium bovis in man and cattle and summarises data derived from surveillance of M. bovis in England and Wales from 1986 to 1990. Of the 228 isolates of 11. bovis examined in this period, 122 (53 %) were from patients aged over 60 years and are largely the result of reactivation of infection acquired prior to the institution of control measures. However, eight isolates (3 5 %) were from patients aged less than 30 years. The potential sources for these presumed primary infections include the few remaining cattle infected with MlI. bovis or infectious human cases in the United Kingdom. However, infections acquired abroad, especially in immigrants, may account for some of these cases. Outbreaks of tuberculosis due to M. bovis continue to occur in cattle. Wild animals, particularly badgers, have been implicated as reservoirs of the infection. However, man may also prove to be an important reservoir of M1. bovis for cattle as well as humans. TNTRODUCTION
The continuing importance of ,M1ycobacterium bovis as a cause of tuberculosis in man was highlighted in a recently published report of an outbreak of M11. bovis infection which originated in a herd of deer [1, 2]. Tuberculosis in man can result from infection with M. tuberculosis, M. bovis and M. africanum, all members of the tubercle bacilli group [3]. The tubercle bacilli group should be distinguished from species of environmental mycobacteria. some of which cause opportunist disease in man. This report discusses the reasons for the change in the relative importance of M. bovis as a cause of tuberculosis in man and the mechanisms through which infection and disease due to iM. bovis continue to occur in man and cattle. HISTORICAL PERSPECTIVE
Today, lkl. bovis aceounts for only about 1 % of all mycobacterial isolates reported in England and Wales. In the first half of the twentieth century. however, it was difficult to assess the considerable proportion of mortality and morbidity due to this infection as disease resulting from infection with
24
R. M. HARDIE AND J. M. WATSON
Table 1. Deaths* due to all forms of tuberculosis in England and Wales in 1931, 1937 and 1944, and estimnatedt number (percentage) of deaths due to M. bovis infection Year... Number of deaths due to tuberculosis (A) Number of deaths due to 1M. bovis (% of A) * OPCS mortality data (1944 t See text.
1931 34959
1937 26926
1944 26434
2 147 (6 1)
1603 (56)
1 638 (62)
figure is average for years 1940-4).
M. tuberculosis, and M1. bovis is clinically indistinguishable [4, 5]. Although the two species can be identified in the laboratory, prior to 1970 the separate species were not routinely reported. In man, the risk of infection with M1. bovis appears to have reduced considerably during this century. Studies from Sweden and the USSR [6, 7] have demonstrated that the prevalence of disease due to M. bovis in cattle correlated with the risk of infection by M. bovis in man. In the 1930s, 40 % of slaughtered cattle in England and Wales had obvious tuberculosis [8] and in 1949 it was estimated that 35 % of dairy cows were infected [9]. In 1950, 18% of herds had at least one infected animal [10], but by 1961 this figure had reduced to 3 5 % [8] and to 0 15 % by 1990
[1 1]. In order to estimate the extent of morbidity and mortality due to M. bovis infection in man prior to 1970, it is necessary to use proxy measures. These are
presented below. (1) In studies in the south of England in 1931 and 1937 it was estimated that about 6% of all forms of tuberculosis were due to M. bovis infection. These proportions were applied to the total number of deaths due to tuberculosis in those years, producing estimates of 2147 and 1603 deaths respectively (Table 1) [12]. Similar methods were used to estimate the number of M. bovis related deaths from respiratory and non-respiratory disease separately: in 1939, 1t4 % of cases of respiratory tuberculosis was estimated to be due to M. bovis [4], and in 1944 a total of 1331 deaths due to non-respiratory tuberculosis was estimated to be due to M. bovis [13]. If the estimate of the proportion of respiratory disease due to M. bovis in 1939 is added to the estimated number of deaths due to non-respiratory disease in 1944, a total of 1638 deaths due to M. bovis infection is estimated for 1944 (Table 1) - 6 2 % of the total, which is consistent with the estimate for the earlier years. (2) In 1955, Lethem used deaths from abdominal tuberculosis in children under 5 years as an index for M. bovis infection [14]. In this age-group this form of tuberculosis was thought to be almost entirely due to ingestion of milk contaminated with M. bovi s. The fall from 1107 deaths in 1921 to 12 deaths in 1953 was much more marked than the equivalent reduction in deaths from other nonpulmonary forms of tuberculosis. This was attributed to the development of 'safe' milk in the intervening years, due to a combination of pasteurization and control of M. bovis infection in cattle. (3) If a high proportion of non-respiratory tuberculosis was formerly due to
M. bovis in England and Wales
25
0
90 70 80 60 50 Year Fig. 1. Tuberculosis notifications in England and XV\ales: non-respiratory notifications as ratio of all tuberculosis notifications. 1920
30
40
M. boriis (estimates varied from 25 to 35 %), then a decline in the proportion of all tuberculosis notifications due to non-respiratory disease might be expected during the period of eradication of bovine tuberculosis. Such a decline is observed from the 1930s to the 1950s (Fig. 1). The subsequent rise in the proportion of nonrespiratory cases may be due to the increasing proportion of notifications in the population of Indian subcontinent (ISC) ethnic origin in whom non-respiratory disease. usually due to M1. tuberculosis, is more common [15]. MODES OF TRANSAISSION ANI) (CONTROL, MI1EASURES Main control measures Two control measures first implemented in the 1930s have resulted in a marked decline in the risk of exposure to Mi. bovis in England and Wales. (1) The Attested Herd Scheme for cattle was implemented as a voluntary control measure in 1935, became compulsory in 1950, and by 1960 all herds were attested. For a dairy or beef herd to maintain attested status, cattle must undergo regular tuberculin tests. Avian and bovine tuberculin are injected at separate sites in the neck skin of the animal and the reactions compared. This reduces the number of false positive reactions which can occur due to cross-sensitization of cattle by Mi. avium-intracellulare, a relatively common infection in cattle which does not result in disease. Most herds are now tuberculin tested 3-yearly. Herds in areas with an increased incidence of bovine tuberculosis are tested annually or biennially. These include areas of Gloucester. Avon, Devon, Cornwall and East Sussex [11]. (2) The process of pasteurization was first described in the middle of the nineteenth century. It was not widely used for milk in the UK until the 1930s when the amount of milk pasteurized under licence inereased considerably. In 1939, 50 % of the population of England and Wales were estimated to be supplied with heat-treated milk [12]. Small dairies in rural districts continued to supply raw milk from non-attested herds until 1960. Although pasteurization is still not a legal requirement in England and Wales, only a very small proportion of milk is not pasteurized and all herds are attested. The last outbreak of tuberculosis due
26
R. M. HARDIE AND J. M. WATSON
to M. bovis was attributed to contaminated milk and occurred in 1959 - three school-children in Yorkshire developed cervical adenitis. The herd responsible was attested but the milk was not pasteurized - the cattle responsible had become infected after the herd was last tuberculin tested [16]. Following the marked reduction in tuberculosis in cattle, cattle in areas with a higher incidence of infection are believed to acquire M. bovis from two major sources: infected badgers, or infected cattle from another farm in the UK or the Republic of Ireland (where there is a higher incidence of bovine tuberculosis). In areas where only sporadic cases occur, the origin of infection is often difficult to establish. Modes of transmission Cattle to cattle A reactor is defined as an animal with a positive comparative reaction to the tuberculin test. All reactors are removed from the herd and slaughtered. Movement restrictions prohibit the transport of cattle onto or off the affected farm until a series of tuberculin tests have been performed with negative results. Approximately one third of reactors are subsequently confirmed to be infected with M. bovis [11]. There are now very few reactors found to have 'open' disease (udder or pulmonary infections) after death. Transmission of infection from cattle with 'open' disease can occur as a result of inhalation or ingestion of infected material. Primary pulmonary infections rarely heal spontaneously in cattle and often result in a highly infectious case. Udder infections only account for 1-2 % of the reactors with 'open' disease [8]. Cattle with 'open' disease may occur in areas where only sporadic cases are found, as the herds are tested 3-yearly and any new infection acquired soon after the last tuberculin test may remain undetected for up to 3 years. Herds in areas with a high incidence of disease are tested annually, so cases are more likely to be detected prior to becoming infectious. To control the spread of disease and identify potential sources of infection, all cattle which have moved into or out of an infected herd are traced and tested where appropriate.
Cattle to human Humans can acquire infection from cattle by consumption of contaminated raw milk or by inhalation of a contaminated aerosol from live infected cattle or infected carcases [17]. Infection could also be acquired by ingestion of infected lymph nodes, but all carcases are inspected at abattoirs and any with involved lymph nodes are condemned. Any positive reactors in a herd which are subsequently confirmed to be infected with M. bovis are notified to the local authority proper officer, usually the Consultant in Communicable Disease Control (CCDC), and human contacts of the herd, particularly farm workers and those with a history of ingestion of raw milk products, are traced. If a dairy herd is involved and unpasteurized milk is being sold from that farm, a pasteurization order may be implemented. A recent report has indicated that transmission to humans, even in large cattle herd outbreaks, is rare [18]. An outbreak of bovine tuberculosis in a beef herd began in April 1990 in South Cumbria, an area previously tested 3-yearly. Among the cattle tuberculin tested in the seven herds ultimately found to be infected, 75
M. bovis in England and Wales
27
positive reactors were subsequently found to have active disease. Twenty human contacts were identified and follow up of these contacts has shown no evidence of infection to date (N. Gent, personal communication). Human to cattle Transmission ofM. tuberculosis from man to cattle has rarely been documented. Evidence for the potential pathogenicity of M. tuberculosis in cattle comes from two sources: first, cattle vaccinated with an 'attenuated' strain of M. tuberculosis in 1913, in the belief that it would protect the cattle from infection with M. bovis, were subsequently found to excrete viable M. tuberculosis, although they were symptomless [19]. Secondly, routine tuberculin testing of herds in the 1950s resulted in the detection of 17 cattle with Mll. tuberculosis infection, although the worst affected animals had only small lesions. suggesting limited pathogenicity. In each case, a history of an infected person working with the cattle was obtained, and no further reactors were detected in any of the herds after removal of the human source [20]. The evidence to date seems to show that. if it occurs, natural infection in cattle with M. tuberculosis does not generally produce progressive disease. By contrast, transmission of Mi. bovis from farm-workers to cattle, with subsequent disease development, is well described [17, 20, 21]. Infection is reported to have been transmitted via the respiratory and genito-urinary tracts. Renal disease is known to occur in a high proportion of human cases (see below) and some farm-workers are reported to urinate habitually in the cowshed. Cattle then acquire the infection by eating the contaminated hay [10].
Human to human Pulmonary disease occurs in only 40-50 % of human cases of tuberculosis due to M. bovis. Of these, some will be sputum smear positive and have the potential to infect others. Indirect evidence for human-to-human transmission of M. bovis comes from two sources: (i) a case series of pulmonary tuberculosis due to M. bovis reported in the 1930s concluded that there was 'bacteriological' evidence of human-to-human transmission [4]; (ii) case reports of disease due to Mi. bovis where all other sources of infection have been excluded [21-23]. However, it remains difficult to determine with certainty the source of human infection due to the lag period of years or decades before clinically evident disease develops. In the future. developments in mycobacterial typing techniques [24] may enable confirmation of suspected episodes of human-to-human transmission.
W'ild animals to cattle or mian Among the wild animal population, badgers are the most important reservoir of
11. bovis infection. There is thought to be a low background level of infection in the badger population, particularly in those areas of the country where spread of infection to cattle is felt to occur more frequently. When infected, badgers may develop outwards signs of disease in the form of infected bite wounds and a high proportion of them develop renal disease. Badgers have a latrine system in which all members of a particular sett use the same well defined areas for urination and defecation. If these areas happen to be on cattle grazing land, the cattle may be exposed to a high concentration of infectious material.
28
R. M. HARDIE AND J. M. WATSON
In the past the main method of controlling this source of infection has been a policy of removing the badgers. Each farm with infected cattle is reviewed separately and, if deemed appropriate, all badgers may be removed from the farm and killed. In 1990, 93 badger removal operations were carried out in the South West, and three elsewhere in England and W"ales. This led to 811 badger carcases being examined, of which 156 (19 %) were infected with M. bovis [11]. This policy does have disadvantages - inevitably some healthy animals are killed and it does not prevent the initial infection of cattle. Prospective action may become possible using a recently developed enzyme-linked immunosorbent assay (ELISA) to detect Mi. bovis infection in badgers [25]. Wild deer also act as a potential reservoir of M. bovis infection. However, they are thought to have a much lower level of infection and their behaviour pattern is very different from that of badgers; in particularly, they have no latrine system. There is felt to be no evidence for wild deer acting as a source of infection for cattle. However, if used for intensive farming, infection in deer could become more prevalent and present more of a risk, not only to cattle but also to humans. This is illustrated by the outbreak of M. bovis infection in Canada which originated in domesticated deer in April 1990 [1]. Of 446 human contacts identified, there was one case of active M. bovis infection in a veterinary surgeon, diagnosed by sputum culture, and 42 people were offered chemoprophylaxis on the basis of tuberculin sensitivity. At present in the UK there is a voluntary Deer Health Scheme for farmed deer in which they undergo regular tuberculin testing. If a positive reactor is found it then becomes compulsory to notify the infected animal to the veterinary authorities.
RECENT DATA SOURCES AND EPIDEMIOLOGY
The PHLS Communicable Disease Surveillance Centre (CDSC) receives reports of isolates of all mycobacteria, including M. bovis, from the 52 Public Health Laboratories and approximately 350 other hospital microbiology laboratories in England and Wales. From January 1986 to October 1991, CDSC received reports of 9687 isolates of mycobacteria. Of these, 8503 (88%) were reported as M. tuberculo8i.s, and 117 (1.2 %) as M. bovis. Data are also available from the six PHLS Regional Tuberculosis Centres (RTCs) and the PHLS Mycobacterium Reference Unit (MRU) to which nearly all mycobacterial isolates are forwarded for further identification and sensitivity testing. Under-reporting of mycobacterial isolates to CDSC from source laboratories is known to occur and the figures from the RTCs and MRU give a more representative picture of the total number of M. bovis isolates examined each year (Fig. 2). Over the last 15 years there has been a reduction in both the number of isolates of M. bovis reported to CDSC and those examined by the MRU and RTCs. The trend observed was more consistent using the data from the MRU and RTCs where a decrease in the number of isolates examined was observed from 127 in 1978 to 31 in 1990. The four regions reporting 20 isolates or more of M. bovis in the period 1986-90 were Northern, Yorkshire. North Western and West Midlands (Fig. 3). As most
M. bovis in England and Wales
29
150-
100 'a C
C._
.0
z
50-
011 1975 76
77 78
79 80
81
82 83
84 85
86
87
88
89
90
Year Fig. 2. M1. bovis isolates. Reports to CDSC (U) and isolates examined by the PHLS RTCs and MRU (s).
Fig. 3. Isolates of M. bovis examined by the six RTCs and the MRU from regions in England and Wales, 1986-90. cases of tuberculosis due to M. bovis are believed to be due to reactivation, and as the prevalence of M. bovis infection in cattle in the past correlated with the risk of infection withM. bovis in man [21, 22], then the regions with the greatest incidence of bovine tuberculosis prior to 1960 would be anticipated to report the greatest number of M. bovis infections in humans. In 1955, six rural districts in Trent, four in West Midlands and one each in Northern, Yorkshire, North West Thames, South Western and Oxford regions were the only remaining rural districts in England and Wales with less than 50 %
R. M. HARDIE AND J. M. WATSON of cattle attested [26]. Thus, three of the four regions with the greatest number of 30
isolates examined over the last 5 years included rural areas which in 1955 had high proportions of unattested herds. Of the isolates examined by the MRU and RTCs from 1986 to 1990, 122/228 (53 %) were from patients aged over 60, 57/228 (25 %) from patients aged 30-60 and 8/228 (3 5 %) from patients aged less than 30 years (Table 2). The remaining isolates were from patients of unknown age. Most cases of tuberculosis due to Mil. bovis occur in the older population and are due to reactivation of primary infection acquired before 1960 (the year when the Attested Herds Scheme became compulsory). Cases in patients aged under 30 years, and an unknown proportion of the others, may be due to primary infections acquired in the UK as a result of contact with infectious disease in a human or from one of the few remaining herds with infected cattle [5. 21, 22]. However, it is likely that at least some of these cases occurred in immigrants from countries with a high risk of M. bovis infection. The data from the RTCs concerning 11. bovis isolates from 1986-90 does not include information about ethnic origin of the patient which is an important determinant of the risk of M. tuberculosis infection in this country. However, in a recent analysis of isolates of M1. bovis from patients in the south-east of England for the years 1977-90 [27] it was reported that, using surnames as an index of nationality, 191/232 (820%) were British, 12/232 (5%) were southern European and 24/232 (10%) were of ISC ethnic origin. The age distribution within these groups differed: the mean age of those with British surnames was 62 years, compared with a mean age of 34 and 29 respectively in the southern European and ISC groups. The sites of disease due to M. bovis infection are shown in Table 3. Disease of the respiratory tract was reported for 78/228 (34%) of isolates. Non-respiratory disease accounted for 123/228 (54%) of the isolates, and the remaining isolates were from cases where the site of disease was unknown, 25/228 (11 %), or from cases of disseminated disease (2/228). Fifty out of 228 isolates (220%) were from the genito-urinary tract. which was the non-respiratory site most frequently associated with isolation of the organism. Lymph node disease, abscesses and cysts accounted for the second largest number of non-respiratory isolates, 41/228 (18 %) Of particular interest are the eight isolates from patients aged less than 30 years. These patients were born in the 1950s or later and their disease is most likely to be due to a primary infection. Of the eight isolates. four (50%) are from a respiratory site, suggesting that the primary infection with 11. bovis in those four patients may have been acquired by inhalation. It has been estimated that, in many rural districts, most tuberculin reactors born prior to 1950 were sensitized byvM. boviis rather thanlM. tuberculosis [26]. This suggests considerable human exposure to M. bovis which is supported by the fact that in the 1930s. 0.5 % of all dairy cows produced milk containing tubercle bacilli [8]. The practice of bulking milk before distribution then increased the risk of exposure to infection in the community. If such a large proportion of the population were infected with M. bovis in their youth, it, might be anticipated that a larger number of infections would now be reported as a result of reactivation than are currently observed. Reasons for the relatively low number of reported infections may include the following.
31
M. bovis in England and Wales
Table 2. Age and sex distribution of patients with isolates of M. bovis examined by the MURU and RTCs in England and Wales in 1986-90 Age (years) < 30 30-60 > 60 Unknown Total
MIale 4 35 57 20 116
Female 4 22 63 18 107
Sex unknown 0 0 2 3 5
Total 8 57 122 41 228
Table 3. Site of disease, and age group. in patients with isolates of M. bovis exarnined by the MRUJ and RTCs in England and Wales in 1986-90 Age (years) Site of isolate
Respiratory Genitio-urinary Gastro-intestinal .Meningeal Abscess/lymph node/cyst Bone/joint Skin/wound Bone marrow Disseminated Unknown Total
< 30 4 0 0 0 2
) 30 60
2 0 0 0 0 8
13 3 1 2 17 179
41
3
L nknown 14 9 1 1
Total
3 0 0 0 8 41
18 3 1 2 25 228
34
78 50
4 6 41
(a) A low reactivation rate of previous infection [5, 28] possibly related to age at infection or route of infection, i.e. infection with M. bovis at an early age, or via the gastrointestinal tract, may result in a reduced rate of reactivation compared with M. tuberculosis infection. (b) A less virulent form of Mll. bovis may now exist, rendered so by previous inadequate pasteurization processes, and resulting in a low incidence of disease in those it infects [26]. (c) Disease caused by Mll. bovis may yield a small proportion of isolates compared with disease caused by Mll. tuberculosis. (d) Failure to identify M. bovis and incomplete reporting of isolates to CDSC [8]. A factor further complicating the available data source is that until the late 1970s M. africanum was frequently mistakenly reported as M. bovis because of their close laboratory resemblance and were sometimes referred to as the 'bovine variants' of M. tuberculosis. However, the epidemiology and characteristics of disease caused by these two mycobacteria differ markedly: M. africanum is not associated with cattle, occurs in the younger immigrant mainly from Africa, and usually results in pulmonary disease [29]. llM. bovis tends to occur in an older age group, in people of white ethnic origin and usually results in extrapulmonary disease [30]. The extent to which national data on M. bovis were affected by mistaken reports is not known. Two studies, one in Liverpool and one in the South East, have attempted to quantify it for those areas [5, 22]. In Liverpool, a very Hy(; 19
R. M. HARDIE
32
AND
J. M. WATSON
low proportion of 'bovine variant' isolates (4/54) were found to be M. africanum. By contrast, the study in the south-east of England found M. africanum ('AfroAsian' bovine strain) not M. bovis ('classical' bovine strain) to account for the majority (74/137) of 'bovine variant' isolates. The reasons for the higher proportion of true M. bovis isolates in Mersey may include the previously high incidence of bovine tuberculosis and the relatively small immigrant population in Mersey compared with the South East. CONCLUSION
Between 20 and 40 isolates of M. boris in humans are currently confirmed each year in England and Wales and this figure has continued to fall over the last 30 years. Reactivated disease is likely to account for most isolates, but some isolates are from patients born after control measures were implemented and may represent a primary infection acquired from cattle or humans, either in the UK or
abroad. The reservoir of potential infection for cattle and deer in the wild animal and human populations means that control measures in cattle and deer herds should be continued indefinitely and outbreaks fully investigated. To this end, it is essential that identification and reporting of M. bovis should continue so that local investigations and control measures can be instituted for each case as necessary. As the age group in the human population with a high incidence of previous infection decreases in size, the number of reports of Mll. bovis isolates is likely to continue to fall. However, if control measures are not strictly adhered to, an increased number of primary infections may occur. ACKNOWLEDGEMIENTS We would like to thank Dr P. A. Jenkins of the Mycobacterium Reference Unit and Mr M. D. Yates of the Regional Tuberculosis Centre at Dulwich for their data and comments. We are indebted to Dr J. M. Grange at the National Heart and Lung Institute for his comments. We gratefully acknowledge data received from Liverpool and Newcastle Regional Tuberculosis Centres. We would also like to thank Mr A. J. Fleetwood and Mr P. Philip, Senior Veterinary Officers at the Ministry of Agriculture, Fisheries and Food and Dr N. Barrett, Principal Scientist at CDSC for their help. REFERENCES 1. Fanning A, Edwards S. Mycobacteriurn bovis infection in human beings in contact with elk (Cervus elaphus) in Alberta, (Canada. Lancet 1991; 338: 1253-55. 2. Editorial. TB and deer farming: return of the king's evil. Lancet 1991; 338: 1243-4. 3. Collins CH, Yates MD, Grange JM. Subdivision of _Mycobacterium tuberculosis into five variants for epidemiological purposes: methods and nomenclature. J Hyg 1982; 89: 235-42. 4. Griffiths AS. Bovine tuberculosis in man. Tubercle 1941; 22: :33-9.
5. XVilkins EGL, Griffiths RJ, Roberts C. Bovine variants of Mycobacteriurn tuberculosis isolates in Liverpool during the period 1969 to 1983: an epidemiological survey. Q J Med 1986; 59: 627-35. 6. Sjogren I, Sutherland I. Studies of tuberculosis in man in relation to infection in cattle. Tubercle 1974; 56: 113-27.
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7. Kovalvov U(K. On human tuberculosis due to AI. botris: a review. J Hyg Epidemiol AMicrobiol linmuniol 1989: 33: 199-206. 8. Collins CH, Grange JMl. The bovine tubercle bacillus. J Appl Bacteriol 1983: 55: 13-29. 9. Savage \V. Milk-borne infections in Great Britain. Brit J Social Med 1949; 3: 45-55. 10. Grange J.M. Collins CH. Bovine tubercle bacilli and disease in animals and main. Epidemiol Infect 1987: 92: 221-34. 11. Animal Health 1990 (The Report of the Chief Veterinary Officer). London: HMlSO. 1991. 12. Wilson US. Pasteurisatioin of milk. Lond)don: Edward Arnold. 1943. 13. Wilson (S. Blacklock .1W. Reillk LV. Non-pulmonary tuberculosis of bovine origini in (great Britain and Northern Irelanid. 1st edition London NAI'T. 1952. 14. Lethem W'A. Milk-borne tuberculosis. 1921 to 1953. Month Bull Mmin Health 1955; 14: 144-5. 1 5j. Medical Research Council Tuberculosis and Chest Diseases tJnit. National survev of notificationis of tuberculosis in Englanid and XV\ales in 1983. Br MNed J 1985: 291: 658-61. 16. George JTA, Payne l)JH. Tuberculosis from T.T. milk, with a note on the frequency of Briucella aborths in consumer milk. Mlonth Bull Mmin Health 1961 ; 20: 99-102. 17. Cutbill L.J. Ly-nn A. 'ulmoonarv tuberculosis of bovine origin. Br Med J 1944: (i): 283-9. 18. Yoxheimer R, Tavris D. Biovine tuberculosis - Pennsylvania. MMZINWR 1990: 39: 201-3. 19. (Griffith AS. Human tubercle bacilli in the milk of a vaccinated cowA. .J Path Bact 1913; 17: 323-8. 20. Lesslie 1W. Cross infections A-ith inmcobacteria betweeni animals and mani. Bull Int UnlioIn Tuberc 1968; 41: 285-8. 21. WNTigle WI). Ashley MLJ, Killough EM. Cosens M. Boviine tuberculosis in humans in Ontario. Am Rev Respir Dis 1972: 106: 5328-34. 22. Collins CH. Yates MI). Grange JAM. A study of bov-ine strains of M1lycobacterium tuberculosis isolated from humnans in South-East Enigland(. 1977-79. Tubercle 1981; 62: 113-16. 23. Kubinl AM. Heralt Z, Alorongova T, Ruzhova R. V'iznerova A. Two cases of probable manto-man transmissioni of Mycobacteriutn bovis. Z Erkr Atmungsorgane 1984; 163: 285-91. 24. Sauniders NA. Analvsis of restriction fragment length polymorphisms in the studv of bacteria. In: (G'range .JM. Fox A. Morgan NL, eds. Genetic manipulation. techniques and applications. Society for Applied Bacteriology Technical Series, No 28. Oxford: Blackwell, 1991:227-44. 25. Mahmood KH, Rook GAW, Staniford JL, Stuart FA, Pritchard DG. The immunological consequences of challenige with bovine tubercle bacilli in badgers (Meles meles). Epidemiol Infect 1987: 98: 155-63. 26. Lesslie I1NW. Mag;nus K, Stewart C.J. The prevalence of bovine type tuberculosis infection in man in the Elnglish rural population. Tubercle 1972: 53: 198-204. 27. Grange JM. Yates MIl). Zoonotic aspects of Mycobaterium boiis infection. Vret Microbiol. in press.
28. Mlagnus K. Mloibidity of respiratory tuberculosis among persons inf'ected from bovine and humani sources. Bull Int Unlionl Tuberc 1964; 35: 349-54. 29. Grange JMl. Yates MD). Incidence and nature of human tuberculosis due to Mycobacteriurm african,uni in South-East England: 1977-1987. Epidemiol Tnfect 1989; 103: 127-32. 30. Yates All). Grange JMl. Incidence and nature of human tuberculosis due to bovine tubercle bacilli in South-East England: 1977-1987. Epidemiol Infect 1988; 101: 225-9.
Epidemiol. Inifect. (1992), 109, 23-33 Printed in Great Britain
Mycobacterium bovis in England and Wales: past, present and future R. M. HARDIE AND J. M. WATSON Respiratory Diseases Section, PHLS Communicable Disease Surveillance Centre, 61, Colindale Avenue, London NIW9 5EQ (Accepted 30 March 1990) SITMMARY
This report reviews the literature concerning tuberculosis resulting from infection with liycobacterium bovis in man and cattle and summarises data derived from surveillance of M. bovis in England and Wales from 1986 to 1990. Of the 228 isolates of 11. bovis examined in this period, 122 (53 %) were from patients aged over 60 years and are largely the result of reactivation of infection acquired prior to the institution of control measures. However, eight isolates (3 5 %) were from patients aged less than 30 years. The potential sources for these presumed primary infections include the few remaining cattle infected with MlI. bovis or infectious human cases in the United Kingdom. However, infections acquired abroad, especially in immigrants, may account for some of these cases. Outbreaks of tuberculosis due to M. bovis continue to occur in cattle. Wild animals, particularly badgers, have been implicated as reservoirs of the infection. However, man may also prove to be an important reservoir of M1. bovis for cattle as well as humans. TNTRODUCTION
The continuing importance of ,M1ycobacterium bovis as a cause of tuberculosis in man was highlighted in a recently published report of an outbreak of M11. bovis infection which originated in a herd of deer [1, 2]. Tuberculosis in man can result from infection with M. tuberculosis, M. bovis and M. africanum, all members of the tubercle bacilli group [3]. The tubercle bacilli group should be distinguished from species of environmental mycobacteria. some of which cause opportunist disease in man. This report discusses the reasons for the change in the relative importance of M. bovis as a cause of tuberculosis in man and the mechanisms through which infection and disease due to iM. bovis continue to occur in man and cattle. HISTORICAL PERSPECTIVE
Today, lkl. bovis aceounts for only about 1 % of all mycobacterial isolates reported in England and Wales. In the first half of the twentieth century. however, it was difficult to assess the considerable proportion of mortality and morbidity due to this infection as disease resulting from infection with
24
R. M. HARDIE AND J. M. WATSON
Table 1. Deaths* due to all forms of tuberculosis in England and Wales in 1931, 1937 and 1944, and estimnatedt number (percentage) of deaths due to M. bovis infection Year... Number of deaths due to tuberculosis (A) Number of deaths due to 1M. bovis (% of A) * OPCS mortality data (1944 t See text.
1931 34959
1937 26926
1944 26434
2 147 (6 1)
1603 (56)
1 638 (62)
figure is average for years 1940-4).
M. tuberculosis, and M1. bovis is clinically indistinguishable [4, 5]. Although the two species can be identified in the laboratory, prior to 1970 the separate species were not routinely reported. In man, the risk of infection with M1. bovis appears to have reduced considerably during this century. Studies from Sweden and the USSR [6, 7] have demonstrated that the prevalence of disease due to M. bovis in cattle correlated with the risk of infection by M. bovis in man. In the 1930s, 40 % of slaughtered cattle in England and Wales had obvious tuberculosis [8] and in 1949 it was estimated that 35 % of dairy cows were infected [9]. In 1950, 18% of herds had at least one infected animal [10], but by 1961 this figure had reduced to 3 5 % [8] and to 0 15 % by 1990
[1 1]. In order to estimate the extent of morbidity and mortality due to M. bovis infection in man prior to 1970, it is necessary to use proxy measures. These are
presented below. (1) In studies in the south of England in 1931 and 1937 it was estimated that about 6% of all forms of tuberculosis were due to M. bovis infection. These proportions were applied to the total number of deaths due to tuberculosis in those years, producing estimates of 2147 and 1603 deaths respectively (Table 1) [12]. Similar methods were used to estimate the number of M. bovis related deaths from respiratory and non-respiratory disease separately: in 1939, 1t4 % of cases of respiratory tuberculosis was estimated to be due to M. bovis [4], and in 1944 a total of 1331 deaths due to non-respiratory tuberculosis was estimated to be due to M. bovis [13]. If the estimate of the proportion of respiratory disease due to M. bovis in 1939 is added to the estimated number of deaths due to non-respiratory disease in 1944, a total of 1638 deaths due to M. bovis infection is estimated for 1944 (Table 1) - 6 2 % of the total, which is consistent with the estimate for the earlier years. (2) In 1955, Lethem used deaths from abdominal tuberculosis in children under 5 years as an index for M. bovis infection [14]. In this age-group this form of tuberculosis was thought to be almost entirely due to ingestion of milk contaminated with M. bovi s. The fall from 1107 deaths in 1921 to 12 deaths in 1953 was much more marked than the equivalent reduction in deaths from other nonpulmonary forms of tuberculosis. This was attributed to the development of 'safe' milk in the intervening years, due to a combination of pasteurization and control of M. bovis infection in cattle. (3) If a high proportion of non-respiratory tuberculosis was formerly due to
M. bovis in England and Wales
25
0
90 70 80 60 50 Year Fig. 1. Tuberculosis notifications in England and XV\ales: non-respiratory notifications as ratio of all tuberculosis notifications. 1920
30
40
M. boriis (estimates varied from 25 to 35 %), then a decline in the proportion of all tuberculosis notifications due to non-respiratory disease might be expected during the period of eradication of bovine tuberculosis. Such a decline is observed from the 1930s to the 1950s (Fig. 1). The subsequent rise in the proportion of nonrespiratory cases may be due to the increasing proportion of notifications in the population of Indian subcontinent (ISC) ethnic origin in whom non-respiratory disease. usually due to M1. tuberculosis, is more common [15]. MODES OF TRANSAISSION ANI) (CONTROL, MI1EASURES Main control measures Two control measures first implemented in the 1930s have resulted in a marked decline in the risk of exposure to Mi. bovis in England and Wales. (1) The Attested Herd Scheme for cattle was implemented as a voluntary control measure in 1935, became compulsory in 1950, and by 1960 all herds were attested. For a dairy or beef herd to maintain attested status, cattle must undergo regular tuberculin tests. Avian and bovine tuberculin are injected at separate sites in the neck skin of the animal and the reactions compared. This reduces the number of false positive reactions which can occur due to cross-sensitization of cattle by Mi. avium-intracellulare, a relatively common infection in cattle which does not result in disease. Most herds are now tuberculin tested 3-yearly. Herds in areas with an increased incidence of bovine tuberculosis are tested annually or biennially. These include areas of Gloucester. Avon, Devon, Cornwall and East Sussex [11]. (2) The process of pasteurization was first described in the middle of the nineteenth century. It was not widely used for milk in the UK until the 1930s when the amount of milk pasteurized under licence inereased considerably. In 1939, 50 % of the population of England and Wales were estimated to be supplied with heat-treated milk [12]. Small dairies in rural districts continued to supply raw milk from non-attested herds until 1960. Although pasteurization is still not a legal requirement in England and Wales, only a very small proportion of milk is not pasteurized and all herds are attested. The last outbreak of tuberculosis due
26
R. M. HARDIE AND J. M. WATSON
to M. bovis was attributed to contaminated milk and occurred in 1959 - three school-children in Yorkshire developed cervical adenitis. The herd responsible was attested but the milk was not pasteurized - the cattle responsible had become infected after the herd was last tuberculin tested [16]. Following the marked reduction in tuberculosis in cattle, cattle in areas with a higher incidence of infection are believed to acquire M. bovis from two major sources: infected badgers, or infected cattle from another farm in the UK or the Republic of Ireland (where there is a higher incidence of bovine tuberculosis). In areas where only sporadic cases occur, the origin of infection is often difficult to establish. Modes of transmission Cattle to cattle A reactor is defined as an animal with a positive comparative reaction to the tuberculin test. All reactors are removed from the herd and slaughtered. Movement restrictions prohibit the transport of cattle onto or off the affected farm until a series of tuberculin tests have been performed with negative results. Approximately one third of reactors are subsequently confirmed to be infected with M. bovis [11]. There are now very few reactors found to have 'open' disease (udder or pulmonary infections) after death. Transmission of infection from cattle with 'open' disease can occur as a result of inhalation or ingestion of infected material. Primary pulmonary infections rarely heal spontaneously in cattle and often result in a highly infectious case. Udder infections only account for 1-2 % of the reactors with 'open' disease [8]. Cattle with 'open' disease may occur in areas where only sporadic cases are found, as the herds are tested 3-yearly and any new infection acquired soon after the last tuberculin test may remain undetected for up to 3 years. Herds in areas with a high incidence of disease are tested annually, so cases are more likely to be detected prior to becoming infectious. To control the spread of disease and identify potential sources of infection, all cattle which have moved into or out of an infected herd are traced and tested where appropriate.
Cattle to human Humans can acquire infection from cattle by consumption of contaminated raw milk or by inhalation of a contaminated aerosol from live infected cattle or infected carcases [17]. Infection could also be acquired by ingestion of infected lymph nodes, but all carcases are inspected at abattoirs and any with involved lymph nodes are condemned. Any positive reactors in a herd which are subsequently confirmed to be infected with M. bovis are notified to the local authority proper officer, usually the Consultant in Communicable Disease Control (CCDC), and human contacts of the herd, particularly farm workers and those with a history of ingestion of raw milk products, are traced. If a dairy herd is involved and unpasteurized milk is being sold from that farm, a pasteurization order may be implemented. A recent report has indicated that transmission to humans, even in large cattle herd outbreaks, is rare [18]. An outbreak of bovine tuberculosis in a beef herd began in April 1990 in South Cumbria, an area previously tested 3-yearly. Among the cattle tuberculin tested in the seven herds ultimately found to be infected, 75
M. bovis in England and Wales
27
positive reactors were subsequently found to have active disease. Twenty human contacts were identified and follow up of these contacts has shown no evidence of infection to date (N. Gent, personal communication). Human to cattle Transmission ofM. tuberculosis from man to cattle has rarely been documented. Evidence for the potential pathogenicity of M. tuberculosis in cattle comes from two sources: first, cattle vaccinated with an 'attenuated' strain of M. tuberculosis in 1913, in the belief that it would protect the cattle from infection with M. bovis, were subsequently found to excrete viable M. tuberculosis, although they were symptomless [19]. Secondly, routine tuberculin testing of herds in the 1950s resulted in the detection of 17 cattle with Mll. tuberculosis infection, although the worst affected animals had only small lesions. suggesting limited pathogenicity. In each case, a history of an infected person working with the cattle was obtained, and no further reactors were detected in any of the herds after removal of the human source [20]. The evidence to date seems to show that. if it occurs, natural infection in cattle with M. tuberculosis does not generally produce progressive disease. By contrast, transmission of Mi. bovis from farm-workers to cattle, with subsequent disease development, is well described [17, 20, 21]. Infection is reported to have been transmitted via the respiratory and genito-urinary tracts. Renal disease is known to occur in a high proportion of human cases (see below) and some farm-workers are reported to urinate habitually in the cowshed. Cattle then acquire the infection by eating the contaminated hay [10].
Human to human Pulmonary disease occurs in only 40-50 % of human cases of tuberculosis due to M. bovis. Of these, some will be sputum smear positive and have the potential to infect others. Indirect evidence for human-to-human transmission of M. bovis comes from two sources: (i) a case series of pulmonary tuberculosis due to M. bovis reported in the 1930s concluded that there was 'bacteriological' evidence of human-to-human transmission [4]; (ii) case reports of disease due to Mi. bovis where all other sources of infection have been excluded [21-23]. However, it remains difficult to determine with certainty the source of human infection due to the lag period of years or decades before clinically evident disease develops. In the future. developments in mycobacterial typing techniques [24] may enable confirmation of suspected episodes of human-to-human transmission.
W'ild animals to cattle or mian Among the wild animal population, badgers are the most important reservoir of
11. bovis infection. There is thought to be a low background level of infection in the badger population, particularly in those areas of the country where spread of infection to cattle is felt to occur more frequently. When infected, badgers may develop outwards signs of disease in the form of infected bite wounds and a high proportion of them develop renal disease. Badgers have a latrine system in which all members of a particular sett use the same well defined areas for urination and defecation. If these areas happen to be on cattle grazing land, the cattle may be exposed to a high concentration of infectious material.
28
R. M. HARDIE AND J. M. WATSON
In the past the main method of controlling this source of infection has been a policy of removing the badgers. Each farm with infected cattle is reviewed separately and, if deemed appropriate, all badgers may be removed from the farm and killed. In 1990, 93 badger removal operations were carried out in the South West, and three elsewhere in England and W"ales. This led to 811 badger carcases being examined, of which 156 (19 %) were infected with M. bovis [11]. This policy does have disadvantages - inevitably some healthy animals are killed and it does not prevent the initial infection of cattle. Prospective action may become possible using a recently developed enzyme-linked immunosorbent assay (ELISA) to detect Mi. bovis infection in badgers [25]. Wild deer also act as a potential reservoir of M. bovis infection. However, they are thought to have a much lower level of infection and their behaviour pattern is very different from that of badgers; in particularly, they have no latrine system. There is felt to be no evidence for wild deer acting as a source of infection for cattle. However, if used for intensive farming, infection in deer could become more prevalent and present more of a risk, not only to cattle but also to humans. This is illustrated by the outbreak of M. bovis infection in Canada which originated in domesticated deer in April 1990 [1]. Of 446 human contacts identified, there was one case of active M. bovis infection in a veterinary surgeon, diagnosed by sputum culture, and 42 people were offered chemoprophylaxis on the basis of tuberculin sensitivity. At present in the UK there is a voluntary Deer Health Scheme for farmed deer in which they undergo regular tuberculin testing. If a positive reactor is found it then becomes compulsory to notify the infected animal to the veterinary authorities.
RECENT DATA SOURCES AND EPIDEMIOLOGY
The PHLS Communicable Disease Surveillance Centre (CDSC) receives reports of isolates of all mycobacteria, including M. bovis, from the 52 Public Health Laboratories and approximately 350 other hospital microbiology laboratories in England and Wales. From January 1986 to October 1991, CDSC received reports of 9687 isolates of mycobacteria. Of these, 8503 (88%) were reported as M. tuberculo8i.s, and 117 (1.2 %) as M. bovis. Data are also available from the six PHLS Regional Tuberculosis Centres (RTCs) and the PHLS Mycobacterium Reference Unit (MRU) to which nearly all mycobacterial isolates are forwarded for further identification and sensitivity testing. Under-reporting of mycobacterial isolates to CDSC from source laboratories is known to occur and the figures from the RTCs and MRU give a more representative picture of the total number of M. bovis isolates examined each year (Fig. 2). Over the last 15 years there has been a reduction in both the number of isolates of M. bovis reported to CDSC and those examined by the MRU and RTCs. The trend observed was more consistent using the data from the MRU and RTCs where a decrease in the number of isolates examined was observed from 127 in 1978 to 31 in 1990. The four regions reporting 20 isolates or more of M. bovis in the period 1986-90 were Northern, Yorkshire. North Western and West Midlands (Fig. 3). As most
M. bovis in England and Wales
29
150-
100 'a C
C._
.0
z
50-
011 1975 76
77 78
79 80
81
82 83
84 85
86
87
88
89
90
Year Fig. 2. M1. bovis isolates. Reports to CDSC (U) and isolates examined by the PHLS RTCs and MRU (s).
Fig. 3. Isolates of M. bovis examined by the six RTCs and the MRU from regions in England and Wales, 1986-90. cases of tuberculosis due to M. bovis are believed to be due to reactivation, and as the prevalence of M. bovis infection in cattle in the past correlated with the risk of infection withM. bovis in man [21, 22], then the regions with the greatest incidence of bovine tuberculosis prior to 1960 would be anticipated to report the greatest number of M. bovis infections in humans. In 1955, six rural districts in Trent, four in West Midlands and one each in Northern, Yorkshire, North West Thames, South Western and Oxford regions were the only remaining rural districts in England and Wales with less than 50 %
R. M. HARDIE AND J. M. WATSON of cattle attested [26]. Thus, three of the four regions with the greatest number of 30
isolates examined over the last 5 years included rural areas which in 1955 had high proportions of unattested herds. Of the isolates examined by the MRU and RTCs from 1986 to 1990, 122/228 (53 %) were from patients aged over 60, 57/228 (25 %) from patients aged 30-60 and 8/228 (3 5 %) from patients aged less than 30 years (Table 2). The remaining isolates were from patients of unknown age. Most cases of tuberculosis due to Mil. bovis occur in the older population and are due to reactivation of primary infection acquired before 1960 (the year when the Attested Herds Scheme became compulsory). Cases in patients aged under 30 years, and an unknown proportion of the others, may be due to primary infections acquired in the UK as a result of contact with infectious disease in a human or from one of the few remaining herds with infected cattle [5. 21, 22]. However, it is likely that at least some of these cases occurred in immigrants from countries with a high risk of M. bovis infection. The data from the RTCs concerning 11. bovis isolates from 1986-90 does not include information about ethnic origin of the patient which is an important determinant of the risk of M. tuberculosis infection in this country. However, in a recent analysis of isolates of M1. bovis from patients in the south-east of England for the years 1977-90 [27] it was reported that, using surnames as an index of nationality, 191/232 (820%) were British, 12/232 (5%) were southern European and 24/232 (10%) were of ISC ethnic origin. The age distribution within these groups differed: the mean age of those with British surnames was 62 years, compared with a mean age of 34 and 29 respectively in the southern European and ISC groups. The sites of disease due to M. bovis infection are shown in Table 3. Disease of the respiratory tract was reported for 78/228 (34%) of isolates. Non-respiratory disease accounted for 123/228 (54%) of the isolates, and the remaining isolates were from cases where the site of disease was unknown, 25/228 (11 %), or from cases of disseminated disease (2/228). Fifty out of 228 isolates (220%) were from the genito-urinary tract. which was the non-respiratory site most frequently associated with isolation of the organism. Lymph node disease, abscesses and cysts accounted for the second largest number of non-respiratory isolates, 41/228 (18 %) Of particular interest are the eight isolates from patients aged less than 30 years. These patients were born in the 1950s or later and their disease is most likely to be due to a primary infection. Of the eight isolates. four (50%) are from a respiratory site, suggesting that the primary infection with 11. bovis in those four patients may have been acquired by inhalation. It has been estimated that, in many rural districts, most tuberculin reactors born prior to 1950 were sensitized byvM. boviis rather thanlM. tuberculosis [26]. This suggests considerable human exposure to M. bovis which is supported by the fact that in the 1930s. 0.5 % of all dairy cows produced milk containing tubercle bacilli [8]. The practice of bulking milk before distribution then increased the risk of exposure to infection in the community. If such a large proportion of the population were infected with M. bovis in their youth, it, might be anticipated that a larger number of infections would now be reported as a result of reactivation than are currently observed. Reasons for the relatively low number of reported infections may include the following.
31
M. bovis in England and Wales
Table 2. Age and sex distribution of patients with isolates of M. bovis examined by the MURU and RTCs in England and Wales in 1986-90 Age (years) < 30 30-60 > 60 Unknown Total
MIale 4 35 57 20 116
Female 4 22 63 18 107
Sex unknown 0 0 2 3 5
Total 8 57 122 41 228
Table 3. Site of disease, and age group. in patients with isolates of M. bovis exarnined by the MRUJ and RTCs in England and Wales in 1986-90 Age (years) Site of isolate
Respiratory Genitio-urinary Gastro-intestinal .Meningeal Abscess/lymph node/cyst Bone/joint Skin/wound Bone marrow Disseminated Unknown Total
< 30 4 0 0 0 2
) 30 60
2 0 0 0 0 8
13 3 1 2 17 179
41
3
L nknown 14 9 1 1
Total
3 0 0 0 8 41
18 3 1 2 25 228
34
78 50
4 6 41
(a) A low reactivation rate of previous infection [5, 28] possibly related to age at infection or route of infection, i.e. infection with M. bovis at an early age, or via the gastrointestinal tract, may result in a reduced rate of reactivation compared with M. tuberculosis infection. (b) A less virulent form of Mll. bovis may now exist, rendered so by previous inadequate pasteurization processes, and resulting in a low incidence of disease in those it infects [26]. (c) Disease caused by Mll. bovis may yield a small proportion of isolates compared with disease caused by Mll. tuberculosis. (d) Failure to identify M. bovis and incomplete reporting of isolates to CDSC [8]. A factor further complicating the available data source is that until the late 1970s M. africanum was frequently mistakenly reported as M. bovis because of their close laboratory resemblance and were sometimes referred to as the 'bovine variants' of M. tuberculosis. However, the epidemiology and characteristics of disease caused by these two mycobacteria differ markedly: M. africanum is not associated with cattle, occurs in the younger immigrant mainly from Africa, and usually results in pulmonary disease [29]. llM. bovis tends to occur in an older age group, in people of white ethnic origin and usually results in extrapulmonary disease [30]. The extent to which national data on M. bovis were affected by mistaken reports is not known. Two studies, one in Liverpool and one in the South East, have attempted to quantify it for those areas [5, 22]. In Liverpool, a very Hy(; 19
R. M. HARDIE
32
AND
J. M. WATSON
low proportion of 'bovine variant' isolates (4/54) were found to be M. africanum. By contrast, the study in the south-east of England found M. africanum ('AfroAsian' bovine strain) not M. bovis ('classical' bovine strain) to account for the majority (74/137) of 'bovine variant' isolates. The reasons for the higher proportion of true M. bovis isolates in Mersey may include the previously high incidence of bovine tuberculosis and the relatively small immigrant population in Mersey compared with the South East. CONCLUSION
Between 20 and 40 isolates of M. boris in humans are currently confirmed each year in England and Wales and this figure has continued to fall over the last 30 years. Reactivated disease is likely to account for most isolates, but some isolates are from patients born after control measures were implemented and may represent a primary infection acquired from cattle or humans, either in the UK or
abroad. The reservoir of potential infection for cattle and deer in the wild animal and human populations means that control measures in cattle and deer herds should be continued indefinitely and outbreaks fully investigated. To this end, it is essential that identification and reporting of M. bovis should continue so that local investigations and control measures can be instituted for each case as necessary. As the age group in the human population with a high incidence of previous infection decreases in size, the number of reports of Mll. bovis isolates is likely to continue to fall. However, if control measures are not strictly adhered to, an increased number of primary infections may occur. ACKNOWLEDGEMIENTS We would like to thank Dr P. A. Jenkins of the Mycobacterium Reference Unit and Mr M. D. Yates of the Regional Tuberculosis Centre at Dulwich for their data and comments. We are indebted to Dr J. M. Grange at the National Heart and Lung Institute for his comments. We gratefully acknowledge data received from Liverpool and Newcastle Regional Tuberculosis Centres. We would also like to thank Mr A. J. Fleetwood and Mr P. Philip, Senior Veterinary Officers at the Ministry of Agriculture, Fisheries and Food and Dr N. Barrett, Principal Scientist at CDSC for their help. REFERENCES 1. Fanning A, Edwards S. Mycobacteriurn bovis infection in human beings in contact with elk (Cervus elaphus) in Alberta, (Canada. Lancet 1991; 338: 1253-55. 2. Editorial. TB and deer farming: return of the king's evil. Lancet 1991; 338: 1243-4. 3. Collins CH, Yates MD, Grange JM. Subdivision of _Mycobacterium tuberculosis into five variants for epidemiological purposes: methods and nomenclature. J Hyg 1982; 89: 235-42. 4. Griffiths AS. Bovine tuberculosis in man. Tubercle 1941; 22: :33-9.
5. XVilkins EGL, Griffiths RJ, Roberts C. Bovine variants of Mycobacteriurn tuberculosis isolates in Liverpool during the period 1969 to 1983: an epidemiological survey. Q J Med 1986; 59: 627-35. 6. Sjogren I, Sutherland I. Studies of tuberculosis in man in relation to infection in cattle. Tubercle 1974; 56: 113-27.
M. bovis in England and Wales
33
7. Kovalvov U(K. On human tuberculosis due to AI. botris: a review. J Hyg Epidemiol AMicrobiol linmuniol 1989: 33: 199-206. 8. Collins CH, Grange JMl. The bovine tubercle bacillus. J Appl Bacteriol 1983: 55: 13-29. 9. Savage \V. Milk-borne infections in Great Britain. Brit J Social Med 1949; 3: 45-55. 10. Grange J.M. Collins CH. Bovine tubercle bacilli and disease in animals and main. Epidemiol Infect 1987: 92: 221-34. 11. Animal Health 1990 (The Report of the Chief Veterinary Officer). London: HMlSO. 1991. 12. Wilson US. Pasteurisatioin of milk. Lond)don: Edward Arnold. 1943. 13. Wilson (S. Blacklock .1W. Reillk LV. Non-pulmonary tuberculosis of bovine origini in (great Britain and Northern Irelanid. 1st edition London NAI'T. 1952. 14. Lethem W'A. Milk-borne tuberculosis. 1921 to 1953. Month Bull Mmin Health 1955; 14: 144-5. 1 5j. Medical Research Council Tuberculosis and Chest Diseases tJnit. National survev of notificationis of tuberculosis in Englanid and XV\ales in 1983. Br MNed J 1985: 291: 658-61. 16. George JTA, Payne l)JH. Tuberculosis from T.T. milk, with a note on the frequency of Briucella aborths in consumer milk. Mlonth Bull Mmin Health 1961 ; 20: 99-102. 17. Cutbill L.J. Ly-nn A. 'ulmoonarv tuberculosis of bovine origin. Br Med J 1944: (i): 283-9. 18. Yoxheimer R, Tavris D. Biovine tuberculosis - Pennsylvania. MMZINWR 1990: 39: 201-3. 19. (Griffith AS. Human tubercle bacilli in the milk of a vaccinated cowA. .J Path Bact 1913; 17: 323-8. 20. Lesslie 1W. Cross infections A-ith inmcobacteria betweeni animals and mani. Bull Int UnlioIn Tuberc 1968; 41: 285-8. 21. WNTigle WI). Ashley MLJ, Killough EM. Cosens M. Boviine tuberculosis in humans in Ontario. Am Rev Respir Dis 1972: 106: 5328-34. 22. Collins CH. Yates MI). Grange JAM. A study of bov-ine strains of M1lycobacterium tuberculosis isolated from humnans in South-East Enigland(. 1977-79. Tubercle 1981; 62: 113-16. 23. Kubinl AM. Heralt Z, Alorongova T, Ruzhova R. V'iznerova A. Two cases of probable manto-man transmissioni of Mycobacteriutn bovis. Z Erkr Atmungsorgane 1984; 163: 285-91. 24. Sauniders NA. Analvsis of restriction fragment length polymorphisms in the studv of bacteria. In: (G'range .JM. Fox A. Morgan NL, eds. Genetic manipulation. techniques and applications. Society for Applied Bacteriology Technical Series, No 28. Oxford: Blackwell, 1991:227-44. 25. Mahmood KH, Rook GAW, Staniford JL, Stuart FA, Pritchard DG. The immunological consequences of challenige with bovine tubercle bacilli in badgers (Meles meles). Epidemiol Infect 1987: 98: 155-63. 26. Lesslie I1NW. Mag;nus K, Stewart C.J. The prevalence of bovine type tuberculosis infection in man in the Elnglish rural population. Tubercle 1972: 53: 198-204. 27. Grange JM. Yates MIl). Zoonotic aspects of Mycobaterium boiis infection. Vret Microbiol. in press.
28. Mlagnus K. Mloibidity of respiratory tuberculosis among persons inf'ected from bovine and humani sources. Bull Int Unlionl Tuberc 1964; 35: 349-54. 29. Grange JMl. Yates MD). Incidence and nature of human tuberculosis due to Mycobacteriurm african,uni in South-East England: 1977-1987. Epidemiol Tnfect 1989; 103: 127-32. 30. Yates All). Grange JMl. Incidence and nature of human tuberculosis due to bovine tubercle bacilli in South-East England: 1977-1987. Epidemiol Infect 1988; 101: 225-9.
