479

tetracycline. These three tetracyclines have similar

pharmacological and antibacterial properties, dosage,and complications. Indeed, their close chemical similarityrobs them partly of therapeutic distinctiveness. A recentaddition to the tetracycline family is demethylchlortetra-cycline, produced by a mutant strain of Streptomycesaureofaciens.6 Owing to its slower renal excretion 7 itprovides higher and more sustained antibacterial activityin the serum than its analogues. 11 Judged by in-vitrosusceptibility of 861 strains of 15 different species ofhuman pathogenic bacteria, demethylchlortetracyclinewas the most active tetracycline analogue, or as active asany other, against two-thirds of all strains; whereaschlortetracycline was more active against some gram-positive organisms, and tetracycline was more active

against some resistant strains of staphylococci.1oChemical manipulations are also changing the face of

erythromycin, first isolated in 1952 11 from Streptomyceserythreus and now a well-established alternative to peni-cillin, notably in the treatment of staphylococcal infections,and also indicated, in conjunction with antitoxin, in themanagement of diphtheria.. Higher blood levels, pro-longed tissue concentrations, satisfactory clinical res-

ponses, and absence of toxicity are now claimed for

propionyl erythromycin lauryl sulphate.12 13The clinician endeavouring to keep abreast finds

difficulty in deciphering new names, official and otherwise,which may relate to new antibiotics, to combinations ofthem, or to fresh analogues. Bewildered also by newdosage schedules, he is likely to retreat to the safety ofhis older, well-tried favourite. Commercial firms evidentlyrecognise his dilemma; for, despite the advantages of thelatest, they continue to produce its predecessors indeference to continuing demand. This is quite unlikeconsumer demand in other industries. Few men would

prefer a 1950 to a 1960 motor-car, and fewer housewiveswould willingly choose a mark-1 washing-machine whenits mark 4 is already on the market.

If the increasing chaos is to be abated, the medicalprofession and the pharmaceutical industry will have towork still more closely together. Controlled clinical trialswill define the relative merits of some agents. Last week,for instance, Dr. Fairbrother and Dr. Taylor 14 describeda comparative trial of penicillins G and B.

ANTISTREPTOLYSIN AND RHEUMATIC FEVER

ACCEPTANCE of the causal association between haemo-lytic streptococcal upper-respiratory infections and acuterheumatism rests largely on serological evidence; butLawy 15 declares that this evidence is being differentlyinterpreted by different workers.

In the past thirty years reports from many parts of theworld have shown with cumulative force that during anacute attack of rheumatic fever antibodies against one ormore of the known antigens of group-A p-hasmolyticstreptococci appear in the patient’s serum in high or6. McCormick, J. R. D., Sjolander, N. O., Hirsch, U., Jensen, E. R.,

Doerschuk, A. P. ibid. 1957, 79, 4561.7. Kunin, C. M., Dornbush, A. C., Finland, M. J. clin. Invest. 1959,

38, 1950.8. Kunin, C. M., Finland, M. New Engl. J. Med. 1958, 259, 999.9. Hirsch, H. A., Finland, M. ibid. 1959, 260, 1099.

10. Hirsch, H. A., Finland, M. Amer. J. med. Sci. 1960, 239, 288.11. McGuire, J. M., Bunch, R. L., Anderson, R. C., Boaz, H. E., Flynn,

E. H., Powell, H. M., Smith, J. W. Antibiot. Chemother. 1952, 2, 281.12. Reichelderfer, T. E., Baird, R. L., Ossofsky, H. J. Antibiotics Annual

1959-60; p. 899.13. Anderson, R. C., Lee, C. C., Worth, H. M., Harris, P. N. J. Amer.

pharm. Ass. scientific edition, 1959, 48, 623.14. Fairbrother, R. W., Taylor, G. Lancet, Aug. 20, 1960, p. 400.15. Lawy, H. S. Ann. rheum. Dis. 1960, 19, 42.

rising titre. This response is specific, and denotes recentinfection with these organisms. The antibody which hasreceived most attention is that directed against streptolysin0-a soluble haemolysin produced by streptococci of thisgroup. Determination of antistreptolysin 0 (A.S.o.) hasbecome a yardstick of streptococcal infection since Todd’soriginal work 16 with this antigen-antibody system. Findingstreptolysin 0 antigenic, he devised a method for titratingA.s.o. which in convenience and reproducibility hasnot been superseded by methods introduced later fordetecting antibodies to other streptococcal antigens.Todd, having shown that A.s.o. responses were

specifically related to haemolytic streptococcal infections,went on to study A.s.o. in rheumatic fever, whose associa-tion with streptococcal infection had been stressed byCoburn. 17 He found that, whether or not a bacterio-logically proved haemolytic streptococcal infection wasobserved before the onset, the sera from patients withrheumatic fever showed raised or rising A.S.O. titres asoften as the sera of patients recovering from uncomplicatedstreptococcal infections. Lawy draws attention once againto the frequency of rise in A.s.o. titre after streptococcalinfections-namely, about 80%. If antibodies to otherstreptococcal antigens (streptokinase, hyaluronidase) areincluded, the figure for serological response approaches100%.The pattern of the A.s.o. response in rheumatic fever has

also been extensively studied. Some of the featuresbelieved by earlier workers to represent a responsecharacteristic of rheumatic fever have not been sub-stantiated. Magnitude of response, for example, is notrelated to severity of attack, nor persistence of titre tochronicity.18 It has been repeatedly confirmed, however,that the antibody response is usually somewhat higher inrheumatic fever than in non-rheumatic streptococcalinfection.1o This corresponds to Stetson’s finding 20 thatthe attack-rate of rheumatic fever after streptococcalinfection is higher in individuals showing a greaterantibody response. This effect may be associated with

repeated streptococcal infection, which, as Rantz 21 hasshown, leads to the early development of an enhancedantistreptococcal response in childhood. But, although inrheumatic fever additional enhancement usually seems tooccur, this is- not an invariable, or even a diagnosticallyuseful, feature. For example, Holborow and Isdale 22found that in very young children with acute rheumatismthe A.s.o. titre may be significantly less raised, and lessoften raised, than in children 8-10 years old.22

In general, the test is clinically useful mainly in detect-ing the imprint of recent streptococcal infection, especiallywhen bacteriological evidence is lacking. In initial attacksand recurrences of rheumatic fever positive serologicalfindings are useful, and in the long-term management ofcases negative tests at intervals provide a check on theefficacy of antibiotic prophylaxis against streptococcalinfections. As Lawy has found, the A.s.o. test may alsobe useful in another non-suppurative complication ofstreptococcal infection-acute nephritis.16. Todd, E. W. Brit. J. exp. Path. 1932, 13, 248; J. Path. Bact. 1938, 47,

423.17. Coburn, A. F. The Factor of Infection in the Rheumatic State. Balti-

more, 1931.18. Stollerman, G. H., Lewis, A. J., Schultz, I., Taranta, A. Amer. J. Med.

1956, 20, 163.19. Anderson, H. C., Kunkel, H. G., McCarty, M. J. clin. Invest. 1948,

27, 425.20. Stetson, C. A. Streptococcal Infections (edited by M. MeCarty); p. 208.

New York, 1954.21. Rantz, L. A., Maroney, M., di Caprio, J. M. Arch. intern. Med. 1951,

87, 360.22. Holborow, E. J., Isdale, I. C. Lancet, 1956, i, 649.