255LEADING ARTICLES

Primary Atypical Pneumonia

THE LANCETLONDON 3 FEBRUARY 1962

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DURING research on virus infections of the respiratorytract there has been a continuous interaction between the

progress of the laboratory worker and the diagnosticprecision of the clinician. For example, when infectionswith influenza virus could be unequivocally recognisedby laboratory methods, it became clear that there was agroup of illnesses, usually called febrile catarrh, whichwere distinct from true influenza though resembling it ina general way. At the same time the clinical picture oftrue epidemic influenza was drawn more precisely bycollecting data from cases in which influenza was con-firmed by laboratory tests.!The concept of primary atypical pneumonia emerged,

and became widely accepted, largely because of Americanwork on epidemics in Servicemen during the secondworld war. Typically, there was a rather long incubationperiod and a prolonged course in which, after prodromalsymptoms, there developed fever, cough, sputum, andlocalised and often migratory signs in the chest. Thechest X-ray showed patchy consolidation, but no

bacterial pathogens were recovered by culture and therewas no response to treatment with sulphonamides orpenicillin. Occasional outbreaks were shown to be dueto the rickettsia of Q fever, but usually no non-bacterialinfection could be detected, though there were sometimesrises in cold-agglutinin titre and in agglutinins for thenon-pathogenic Streptococcus MG. Small outbreaks ofsuch a disease have been reported from time to time inBritain and rises of cold-agglutinins and Strep. MGagglutinins have been found.2 3

In 1944, EATON 4 inoculated chick embryos with

sputums from patients with atypical pneumonia. Therewas no evidence of infection, but in hamsters and cotton-rats inoculated with chick-embryo material lung lesionsdeveloped. The technique was very difficult, and fewworkers were able to repeat EATON’s results. Over ten

years later, however, LiU5 5 cut sections of the lungs ofembryos infected with the Eaton agent and stained themfor the presence of virus antigen with fluorescein-

conjugated antibody. The antigen was found in theepithelium of the lower respiratory tract. This tech-

nique made possible the detection of specific antibodyas well as of infected embryos, and Liu made numbers1. Stuart-Harris, C. H., Andrewes, C. H., Smith, W., Chalmers, D. K. M.,

Cowen, E. G. H., Hughes, D. L. Spec. Rep. Ser. med. Res. Coun.,Lond. 1938, no. 228.

2. Anderson, T. B. Lancet, 1960, i, 1375.3. Stuart-Harris, C. H. Brit. med. J. 1950, ii, 1457.4. Eaton, M.D., Meiklejohn, G., van Herick, W. J. exp. Med. 1944, 79, 649.5. Liu, C. ibid. 1957, 106, 455.

of isolations from patients with the disease. Though theagent has been propagated as though it were a virus, itnow seems that it is a pleuropneumonia-like organism(mycoplasma), but it has not so far been grown in theabsence of living cells. 6

Recently a large controlled epidemiological investiga-tion of respiratory illness in Parris Island, where U.S.Marines are trained, produced solid evidence that theagent causes primary atypical pneumonia and probablysome milder respiratory disease as well, and that cir-culating antibody protects against disease. 7

Meanwhile, it had been shown that infection of therespiratory tract with adenoviruses, which usuallyproduce pharyngitis, may present as the syndrome ofprimary atypical pneumonia, though in such cases therewas no rise in the cold-agglutinin or Strep. MG titre.8 8These new laboratory techniques have now been usedto define the clinical features of virus pneumonia due toknown aetiological agents and seen on Parris Island.9 9109 cases of Eaton-agent pneumonia and 23 cases ofadenovirus pneumonia were studied by repeated clinicalexamination, X-rays, and routine laboratory tests. Thegeneral pattern of illness was similar to that described inother studies. After a few days’ fever, headache, andother constitutional symptoms, cough developed. 84%of cases had rales in the chest, and X-ray examinationusually showed unilateral pulmonary infiltration. In

19% of cases it was bilateral. Symptoms and signssometimes progressed, but most patients were improvingin 3 to 10 days, though chest signs and symptoms per-sisted for 7 to 21 days. Cold agglutinins developed in45 % of cases, and these infections were more severe thanthe others. Though practically never fatal, this infectioncan clearly produce an unpleasant and protracted illness.Adenovirus pneumonia was similar, but coryza and

signs in the throat were commoner, the disease wasmilder and ended sooner, and there were no rises in

cold-agglutinins.These results are of practical importance, for it has

now been shown in a very careful inquiry by the sameworkers that a tetracycline antibiotic (demethylchlor-tetracycline) has a therapeutic effect on Eaton-agentpneumonia 10 (previous studies on this subject wereinconclusive). On the other hand, antibiotic treatmentwill not affect adenovirus pneumonia. There is at

the moment, however, no rapid diagnostic test forthese diseases, because virus isolation is a slowbusiness. Perhaps the new fluorescent-antibody tech-nique could be applied to cells in sputum and

provide an answer quickly enough to help in the treat-ment of this syndrome. Meanwhile, if it is possible, atthe beginning of an outbreak of such a disease, to deter-mine whether cold agglutinins or antibodies againstadenoviruses are appearing in the early cases, thentreatment could be more rationally planned.6. Marmion, B. P., Goodburn, G. M. Nature, Lond. 1961, 189, 247.7. Chanock, R. M., Mufson, M. A., Bloom, H. H., James, W. D., Fox,

H. H., Kingston, J. R. J. Amer. med. Ass. 1961, 175, 213.8. Dascombe, M. E., Hilleman, M. R. Amer. J. Med. 1956, 21, 161.9. Mufson M. A., Manko, M. A., Kingston, J. R., Chanock, R. M.

J. Amer. med. Ass. 1961, 178, 369.10. Kingston, J. R., Chanock, R. M., Mufson, M. A., Hellman, L. P.,

James, M. D., Fox., H. H., Manko, M. A., Boyers, J. ibid. 1961, 176, 118.