SPEGFIC BACTERIAL PATHOGENS THEIR UMPORTANCE AND CONTROL
It is gratifying that, after a very long delay in publicstion, the article by Millar and Francis (1974) should have attracted such a prompt response from? i i r Hughes. The main purpose of his letter appexs to be to contest the view of Millar and Francis fhat a mare carryiqg a certain number of potentially pathogenic organisms (particularly haemolytic streptococci) in the reproductive tract, is less likely to produce a foal than an animal free of such organisms, or at least to assert that this proposition is unproven. A general knowledge of bacteriology and infectious diseases would, of course, lead one t o accept our view and it should be necessary for those who disagree to prove that the presence of these potential pathogens is not harmful. Hughes refers to a Thesis of 1956 but it is made clear that the paper is not based solely on the Thesis. He does not quote accurately in his second paragraph. Actually, we said: “In this study the results were decisive in that 80% of mares that were clinically normal and free from infection produced foals, whereas only 52% of clinically normal mares with infection produced foals, although the mean ages of these two groups were almost identical. Only 19% of mares with infection and injury produced foals.” And I again assert that the difference between 80% and 52% is a decisive difference: it is significant at the 1% level. With modern techniques, streptococci would doubtless have been isolated from a higher proportion of mares although it should be noted that ow percentage incidence was 15.6% compared to 9.3% in a large survey in England. However, the sensitivity of the method does not affect the general validity of the results. The method of examination used would, on the average, detect a certain level of infection and what the paper shows is that, on the average, mares with that level of infection are less likely to produce a foal than mares that do not have this population of potentially pathogenic bacteria. If, as Hughes states, a proportion of the mares classified as free from infection (Groups 1 and 2) were, in fact, infected it could be argued that this would have tended to reduce the difference in fertility observed between the groups classified as infected or uninfected. Hughes also disputes the significance of certain results obtained by Bain (1960) but Bain’s overall findings showed that beta-haemolytic streptococci were the most serious pathogens encountered and only 40% of mares infected with these organisms produced a live foal in the first year after examination. Within a 3-year period only 65% had completed a successful pregnancy. On the other hand his Table 4 shows that, of mares from which no bacteria were isolated, 65% became pregnant in the same year and 90% became pregnant within 3 years. With groups of 175 and 185 mares respectively, the possibility of these differences being due to chance is about 1 in 10,000. Many of the current attitudes to haemolytic streptococci in the reproductive tract are largely influenced by the fact that, at present, there are no clear ideas on how to control these infections. However, in the past people had even less knowledge of how to control other infections and have been very confused about the causal relationship between certain bacteria and disease although with many diseases, these things are now regarded as simple and obvious. Some account of how this knowledge and understanding, and thus methods of control, developed will therefore be useful in this discussion. One may cite the opposition to the view that Vibrio cholerae was the cause of cholera long after Koch’s Australian Veterinary Journal, Vol. 51, May, 1975
anouncement of this in 1884. The account of the Seventh International Sanitary Conference in 1892 (Howard-Jones 1974) describes how Sir John BurdonSanderson, Professor of Physiology and then Regius Professor of Medicine at Oxford, affirmed that “the theory of Dr Koch” was “not supported by any adequate evidence” and was “an unfortunate fiasco”. All sorts of epidemic influences were dismssed and Pettenkofer dismissed the report of the German Commission on the grounds that it consisted of “outspoken contagionists” and “drinking water theoreticians”: this was 33 years after Snow’s definitive publication in England showing the connection between drinking water and cholera. Aristotle did believe in the infectivity of tuberculosis but commenting on Koch’s discovery of the tubercle bacillus announced in 1882, Dr (later Sir Clifford) Allbutt, Regius Professor of Physic in the University of Cambridge, said that “although his attention had been given for many years to this question, he had never observed a case of even probable transmision of phthisis from one person to another.” (Cobbett 1917). Thus, in opposing the evidence that a certain disease, or condition, is caused by a specific bacterial pathogen, Hughes is in good company even if, like his distinguished predecessors, he is, as I believe, wrong. The epidemiology of haemolytic (Group C ) streptococci in the horse is very similar to that of haemolytic (Group A) streptococci in man. We were graphically told in the C r y and the Covenant, by M. Thompson, how Semmelveiss was able to reduce the mortality from puerperal sepsis from about 20% to 0.85% if those attending women in the lying-in hospitals washed their hands in chloride of lime: but the medical profession continued to believe that the disease was due to overcrowding, the onset of lactation, or a “miasma”. Poor Semmelveiss became mentally deranged because of the opposition to his simple and successful methods. He died in 1865 and it was many years before effective measures for the control of this disease were taken, Hughes suggests that our analogy with Str. agalacliae is invalid because “Str. agalactiae has been shown to be solely an inhabitant of the mammary gland and teat canal of cattle, whereas Str. zooepidernicus can be isolated from a wide range of sites in normal horses, especially lymph nodes, skin and vulva1 labiae”. In this he is largely correct although Str. ugulcrctiue does colonise the skin. But it is not long ago that a Report ( 1944) from the Agricultural Research Council reflected the then general view that Str. agalactiae could be isolated from many sites in the infected herd and cowshed. It was stated that “The results of the tests on the individual cattle within these herds varied so widely from one weekly test to another, that no one test would have given a correct picture of the distribution of the milk or teat infections.” (Here we have the bogey of “infection status” raised by Hughes). The Report concluded that “the picture which emerged was a disturbing one” and that it was unlikely that there would be any practicable means for eliminating Str. ugalacliae infection from a large number of herds. In Australia Munch-Petersen et a1 ( 1940) had expressed similar pessimistic views and around this time there was much discussion concerning latent infection “infection status” and various predisposing causes, These were discussed by Francis (1941a) who drew attention to the possible influence of hormones on susceptibility and Berger and Francis ( 1951) did report the relatively high incidence of mastitis during the first month after calving, and the 283
equally high incidence during the preceding 3 months of the dry period, as striking observations. They also found that the total incidence of mastitis was much greater during the third quarter of the year than in any other quarter and that, in England, all forms of mastitis were much less common during May and June than in other months. Despite the above complications successful work on eradication of Sir. agalactiae, with the aid of chemotherapy, was reported by Francis (1949) and in Australia by Frast and Sanderson (1965). At this time however, there was still much scepticism concerning the possibility of effective measures for the control of mastitis caused by staphyloccoci. Francis (1941b) isolated staphylococci, and most other organisms that cause mastitis from the tonsils and vaginas of cattle but has been unable to isolate Str. agalactiae and it is now accepted that the udder is virtually the only habitat of Str. agalactiae but that staphylococci, like haemolytic streptococci in man (Group A ) and horses (Group C), can be isolated from many different sites. Nevertheless work on control has continued and Neave and Jackson (1971) concluded that there is no immediate prospect of preventing new intramainmary infections with Str. agaloctiae by immunisation or by breeding resistant cows but that this organism can be eradicated from herds and, although more difficult, it is also possible to eradicate Staph. aureus. Some may question the last statement but it is certainly true that the prevalence of staphylococcal infection can be much reduced by teatdipping. So once again we see that sensible and practical measures to control an apparently ubiquitous bacterial pathogen can be successful in preventing disease and one may perhaps conclude by returning to tuberculosis. In 1901 a certain Mr Goodall had maintained that the tubercle bacillus had little importance in itself and that predisposing causes were the all-important factors in the incidence and severity of the disease. M’Fadyean, like most leading veterinarians since about 1860 had a clear concept of infectious diseases and in two editorial articles (Anon 1901 a, b), that would well repay study by anyone interested in scientific debate, M’Fadyean rebutted the views of $+i Goodall and concluded the first article by saying: ‘“he man whose sense of proportion is not hopelessly defective will attach only minor importance to such considerations (sound constitution and perfect mucous membranes) and will concentrate his efforts against the one great cause of the disease - the operation of contagion. When that has been successfully grappled with predisposition becomes of no account, and as long as it is neglected the endeavour to stay the progress of the disease by any other method is as hopeless as the search for the philosopher’s stone.” Hughes seems to believe that because group C s t r e p tococci are “ubiquitous” in horses they are unlikely to be the cause of a certain disease condition (lowered fertility) but they are not more ubiquitous than group A streptococci in man or staphylococci in cattle and he would hardly deny that the latter organism may be the cause of chronic, or sometimes acute, mastitis, even if we do not understand the predisposing factors.
284
Of the 225 mares reported on by Millar and Francis (1974) 50% became pregnant and the consequences of infection may be clearer if injury is disregarded. We then find that, with the techniques used, of 92 mares free from infection 70% produced a viable foal; of 98 infected with organisms other than haemolytic streptococci 39% produced a viable foal; of 35 mares infected with haemolytic streptococci 20% produced a viable foal. Most people would accept these figures as indicating that bacterial infection is harmful and that haemolytic streptococci are particularly disadvantageous. It is not easy to carry out a planned clinical study of this type, combined with bacteriological examinations, and we are indebted to Mr Millar for being the first person to make such observations. Doubtless a number of things could have been better done but it is my considered opinion that another trial, carried out with the techniques now available, would give essentially similar results. When once these results are accepted, and their importance in relation to infertility understood by the profession, means will be found to “concentrate efforts against the one great cause of infertility - “the operation of contagion”: it is only when this has been grappled with that there will be a decisive improvement in equine fertilitv as there has been in the control of cholera, tuberculosis, puerperal sepsis and mastitis caused by Str. agalactiae as well as the more ubiquitous staphylococci. It should be noted that in our study 80% of clinically sound mares that were free from infection, as judged by methods then available, produced a foal. J.
FRANCIS, D.Sc. (Lond.), MSc. (Vet. Sc.), F.R.C.V.S., F.R.S.M. (Lond.), Hon. Dip. Am. Vet. Epid. SOC. Professor of Preventive Medicine, Veterinary School, University of Queensland, St. Lucia, Queensland, 4067. 7 January 1975
References Anon (1901a)-I. comp. Path. 14: 285. Anon (1901b&I. comp. Path. 14: 354. Bain, A. M. (1966bVet. Rec. 78: 168. Berger, J . and Francis, J. ( 1 9 5 l h V e t . Rec. 63: 283. Cobbett, L. ( 1 9 1 7 b T h e Causes of Tuberculosis, Cambridge. p 707. Francis, J. (1941ahVet. Rec. 53: 395. Francis, J. (1941bhVet. I. 97: 243. Francis, J. (1949b.l. comp. Path. 59: 225. Frost, A. J. and Sanderson, C. I. (1965)-Ausr. vet. I. 41: 97. Howard-Jones, N. ( 1 9 7 4 b W H O Chron. 28: 414. Millar, R. and Francis, J. (1974)-Aust. vet. I. 50: 351. Munch-Peterson, E., Murnane, D. and Bull, L. B. (1940) -Bull. Counc. scient. ind. Res., Aust., No. 134, p 107. Neave, F. K. and Jackson, E. R. (1971)-in The Control of Bovine Mastilis, Eds. Dodd, F. H. and Jackson, E. R., Reading, England. p 15. Report (1944bModes of Spread of Str. agalactiae Infection in Dairy Herds, Imp. Bur. Anim. Hlth, New Haw, England. p 27.
Australian Veterinary Journal, Vol. 51, May, 1975
It is gratifying that, after a very long delay in publicstion, the article by Millar and Francis (1974) should have attracted such a prompt response from? i i r Hughes. The main purpose of his letter appexs to be to contest the view of Millar and Francis fhat a mare carryiqg a certain number of potentially pathogenic organisms (particularly haemolytic streptococci) in the reproductive tract, is less likely to produce a foal than an animal free of such organisms, or at least to assert that this proposition is unproven. A general knowledge of bacteriology and infectious diseases would, of course, lead one t o accept our view and it should be necessary for those who disagree to prove that the presence of these potential pathogens is not harmful. Hughes refers to a Thesis of 1956 but it is made clear that the paper is not based solely on the Thesis. He does not quote accurately in his second paragraph. Actually, we said: “In this study the results were decisive in that 80% of mares that were clinically normal and free from infection produced foals, whereas only 52% of clinically normal mares with infection produced foals, although the mean ages of these two groups were almost identical. Only 19% of mares with infection and injury produced foals.” And I again assert that the difference between 80% and 52% is a decisive difference: it is significant at the 1% level. With modern techniques, streptococci would doubtless have been isolated from a higher proportion of mares although it should be noted that ow percentage incidence was 15.6% compared to 9.3% in a large survey in England. However, the sensitivity of the method does not affect the general validity of the results. The method of examination used would, on the average, detect a certain level of infection and what the paper shows is that, on the average, mares with that level of infection are less likely to produce a foal than mares that do not have this population of potentially pathogenic bacteria. If, as Hughes states, a proportion of the mares classified as free from infection (Groups 1 and 2) were, in fact, infected it could be argued that this would have tended to reduce the difference in fertility observed between the groups classified as infected or uninfected. Hughes also disputes the significance of certain results obtained by Bain (1960) but Bain’s overall findings showed that beta-haemolytic streptococci were the most serious pathogens encountered and only 40% of mares infected with these organisms produced a live foal in the first year after examination. Within a 3-year period only 65% had completed a successful pregnancy. On the other hand his Table 4 shows that, of mares from which no bacteria were isolated, 65% became pregnant in the same year and 90% became pregnant within 3 years. With groups of 175 and 185 mares respectively, the possibility of these differences being due to chance is about 1 in 10,000. Many of the current attitudes to haemolytic streptococci in the reproductive tract are largely influenced by the fact that, at present, there are no clear ideas on how to control these infections. However, in the past people had even less knowledge of how to control other infections and have been very confused about the causal relationship between certain bacteria and disease although with many diseases, these things are now regarded as simple and obvious. Some account of how this knowledge and understanding, and thus methods of control, developed will therefore be useful in this discussion. One may cite the opposition to the view that Vibrio cholerae was the cause of cholera long after Koch’s Australian Veterinary Journal, Vol. 51, May, 1975
anouncement of this in 1884. The account of the Seventh International Sanitary Conference in 1892 (Howard-Jones 1974) describes how Sir John BurdonSanderson, Professor of Physiology and then Regius Professor of Medicine at Oxford, affirmed that “the theory of Dr Koch” was “not supported by any adequate evidence” and was “an unfortunate fiasco”. All sorts of epidemic influences were dismssed and Pettenkofer dismissed the report of the German Commission on the grounds that it consisted of “outspoken contagionists” and “drinking water theoreticians”: this was 33 years after Snow’s definitive publication in England showing the connection between drinking water and cholera. Aristotle did believe in the infectivity of tuberculosis but commenting on Koch’s discovery of the tubercle bacillus announced in 1882, Dr (later Sir Clifford) Allbutt, Regius Professor of Physic in the University of Cambridge, said that “although his attention had been given for many years to this question, he had never observed a case of even probable transmision of phthisis from one person to another.” (Cobbett 1917). Thus, in opposing the evidence that a certain disease, or condition, is caused by a specific bacterial pathogen, Hughes is in good company even if, like his distinguished predecessors, he is, as I believe, wrong. The epidemiology of haemolytic (Group C ) streptococci in the horse is very similar to that of haemolytic (Group A) streptococci in man. We were graphically told in the C r y and the Covenant, by M. Thompson, how Semmelveiss was able to reduce the mortality from puerperal sepsis from about 20% to 0.85% if those attending women in the lying-in hospitals washed their hands in chloride of lime: but the medical profession continued to believe that the disease was due to overcrowding, the onset of lactation, or a “miasma”. Poor Semmelveiss became mentally deranged because of the opposition to his simple and successful methods. He died in 1865 and it was many years before effective measures for the control of this disease were taken, Hughes suggests that our analogy with Str. agalacliae is invalid because “Str. agalactiae has been shown to be solely an inhabitant of the mammary gland and teat canal of cattle, whereas Str. zooepidernicus can be isolated from a wide range of sites in normal horses, especially lymph nodes, skin and vulva1 labiae”. In this he is largely correct although Str. ugulcrctiue does colonise the skin. But it is not long ago that a Report ( 1944) from the Agricultural Research Council reflected the then general view that Str. agalactiae could be isolated from many sites in the infected herd and cowshed. It was stated that “The results of the tests on the individual cattle within these herds varied so widely from one weekly test to another, that no one test would have given a correct picture of the distribution of the milk or teat infections.” (Here we have the bogey of “infection status” raised by Hughes). The Report concluded that “the picture which emerged was a disturbing one” and that it was unlikely that there would be any practicable means for eliminating Str. ugalacliae infection from a large number of herds. In Australia Munch-Petersen et a1 ( 1940) had expressed similar pessimistic views and around this time there was much discussion concerning latent infection “infection status” and various predisposing causes, These were discussed by Francis (1941a) who drew attention to the possible influence of hormones on susceptibility and Berger and Francis ( 1951) did report the relatively high incidence of mastitis during the first month after calving, and the 283
equally high incidence during the preceding 3 months of the dry period, as striking observations. They also found that the total incidence of mastitis was much greater during the third quarter of the year than in any other quarter and that, in England, all forms of mastitis were much less common during May and June than in other months. Despite the above complications successful work on eradication of Sir. agalactiae, with the aid of chemotherapy, was reported by Francis (1949) and in Australia by Frast and Sanderson (1965). At this time however, there was still much scepticism concerning the possibility of effective measures for the control of mastitis caused by staphyloccoci. Francis (1941b) isolated staphylococci, and most other organisms that cause mastitis from the tonsils and vaginas of cattle but has been unable to isolate Str. agalactiae and it is now accepted that the udder is virtually the only habitat of Str. agalactiae but that staphylococci, like haemolytic streptococci in man (Group A ) and horses (Group C), can be isolated from many different sites. Nevertheless work on control has continued and Neave and Jackson (1971) concluded that there is no immediate prospect of preventing new intramainmary infections with Str. agaloctiae by immunisation or by breeding resistant cows but that this organism can be eradicated from herds and, although more difficult, it is also possible to eradicate Staph. aureus. Some may question the last statement but it is certainly true that the prevalence of staphylococcal infection can be much reduced by teatdipping. So once again we see that sensible and practical measures to control an apparently ubiquitous bacterial pathogen can be successful in preventing disease and one may perhaps conclude by returning to tuberculosis. In 1901 a certain Mr Goodall had maintained that the tubercle bacillus had little importance in itself and that predisposing causes were the all-important factors in the incidence and severity of the disease. M’Fadyean, like most leading veterinarians since about 1860 had a clear concept of infectious diseases and in two editorial articles (Anon 1901 a, b), that would well repay study by anyone interested in scientific debate, M’Fadyean rebutted the views of $+i Goodall and concluded the first article by saying: ‘“he man whose sense of proportion is not hopelessly defective will attach only minor importance to such considerations (sound constitution and perfect mucous membranes) and will concentrate his efforts against the one great cause of the disease - the operation of contagion. When that has been successfully grappled with predisposition becomes of no account, and as long as it is neglected the endeavour to stay the progress of the disease by any other method is as hopeless as the search for the philosopher’s stone.” Hughes seems to believe that because group C s t r e p tococci are “ubiquitous” in horses they are unlikely to be the cause of a certain disease condition (lowered fertility) but they are not more ubiquitous than group A streptococci in man or staphylococci in cattle and he would hardly deny that the latter organism may be the cause of chronic, or sometimes acute, mastitis, even if we do not understand the predisposing factors.
284
Of the 225 mares reported on by Millar and Francis (1974) 50% became pregnant and the consequences of infection may be clearer if injury is disregarded. We then find that, with the techniques used, of 92 mares free from infection 70% produced a viable foal; of 98 infected with organisms other than haemolytic streptococci 39% produced a viable foal; of 35 mares infected with haemolytic streptococci 20% produced a viable foal. Most people would accept these figures as indicating that bacterial infection is harmful and that haemolytic streptococci are particularly disadvantageous. It is not easy to carry out a planned clinical study of this type, combined with bacteriological examinations, and we are indebted to Mr Millar for being the first person to make such observations. Doubtless a number of things could have been better done but it is my considered opinion that another trial, carried out with the techniques now available, would give essentially similar results. When once these results are accepted, and their importance in relation to infertility understood by the profession, means will be found to “concentrate efforts against the one great cause of infertility - “the operation of contagion”: it is only when this has been grappled with that there will be a decisive improvement in equine fertilitv as there has been in the control of cholera, tuberculosis, puerperal sepsis and mastitis caused by Str. agalactiae as well as the more ubiquitous staphylococci. It should be noted that in our study 80% of clinically sound mares that were free from infection, as judged by methods then available, produced a foal. J.
FRANCIS, D.Sc. (Lond.), MSc. (Vet. Sc.), F.R.C.V.S., F.R.S.M. (Lond.), Hon. Dip. Am. Vet. Epid. SOC. Professor of Preventive Medicine, Veterinary School, University of Queensland, St. Lucia, Queensland, 4067. 7 January 1975
References Anon (1901a)-I. comp. Path. 14: 285. Anon (1901b&I. comp. Path. 14: 354. Bain, A. M. (1966bVet. Rec. 78: 168. Berger, J . and Francis, J. ( 1 9 5 l h V e t . Rec. 63: 283. Cobbett, L. ( 1 9 1 7 b T h e Causes of Tuberculosis, Cambridge. p 707. Francis, J. (1941ahVet. Rec. 53: 395. Francis, J. (1941bhVet. I. 97: 243. Francis, J. (1949b.l. comp. Path. 59: 225. Frost, A. J. and Sanderson, C. I. (1965)-Ausr. vet. I. 41: 97. Howard-Jones, N. ( 1 9 7 4 b W H O Chron. 28: 414. Millar, R. and Francis, J. (1974)-Aust. vet. I. 50: 351. Munch-Peterson, E., Murnane, D. and Bull, L. B. (1940) -Bull. Counc. scient. ind. Res., Aust., No. 134, p 107. Neave, F. K. and Jackson, E. R. (1971)-in The Control of Bovine Mastilis, Eds. Dodd, F. H. and Jackson, E. R., Reading, England. p 15. Report (1944bModes of Spread of Str. agalactiae Infection in Dairy Herds, Imp. Bur. Anim. Hlth, New Haw, England. p 27.
Australian Veterinary Journal, Vol. 51, May, 1975
