Second Attacks of Pneumonia Due to Mycoplasma pneumoniae

Transcription

1 THE JOURNAL OF NFECTOUS DSEASES. VOL. 135, 1\0. 4 APRL by the University f Chicag. All rights reserved. Secnd Attacks f Pneumnia Due t Mycplasma pneumniae Hjrdis M. Fay, Gerge E. Kenny, Richard Sefi, Hans D. Ochs, and nez D. Allan Frm the Departments f Epidemilgy and Pathbilgy, Schl f Public Health and Cmmunity Medicine; and the Department f Pediatrics, Schl f Medicine, University f Washingtn; and the Grup Health Cperative f Puget Sund, Seattle, Washingtn Lng-term surveillance f pneumnia in a grup that received prepaid medical care disclsed five cases f pneumnia due t Mycplasma pneumniae that recurred in immuncmpetent persns after a lapse f tw and ne-half t 10 years. Diagnsis was cnfirmed by islatin f A. pneumniae, by bservatin f changes in titer f antibdy, and by chest films. n additin, a patient with a variable immundeficiency syndrme that affected the bne marrw-derived (B-) cell system had recurrent infectin with A. pneumniae within a ne-year interval. Naturally acquired immunity t infectin with M. pneumniae appears t be f limited duratin. Pneumnia due t Mycplasma pneurnniae has been studied in Seattle since 1962 in a grup that received prepaid medical care [1]. The appraisal f the ttal incidence f this illness was begun in 1963 [2, 3]. The verall incidence was 1.7 episdes per 1,000 persns per year; rates were highest in thse aged five t 15 years, relatively lw amng adults, and especially lw amng the elderly [2]. This pattern suggested that infectin during childhd may result in durable immunity t M. pneumniae pneumnia. Hwever, in 1970, fur and ne-half years after the riginal illness, a case f repeated M. pneumniae pneumnia was diagnsed in a 40-year-ld husewife; n bth ccasins the etilgy f the illness was cnfirmed by islatin f the agent, rises in titer f antibdy, and radilgical infiltrates seen n chest films [4]. Between 1970 and 1974 we bserved fur additinal cases f repeated M. pneum n iae pneumnia in lder teenagers and yung adults wh had experienced their first illness tw and ne-half t 10 years previusly. n additin, Received fr publicatin May 24, 1976, and in revised frm September 27, This investigatin was supprted by research grants n. A and A frm the Natinal nstitute f Allergy and nfectius Diseases, Natinal nstitutes f Health and by grant n. RR-37 frm the U.S. Public Health Service. Dr. Ochs is an investigatr f the Hward Hughes Medical nstitute, Miami, Flrida. Please address requests fr reprints t Dr. H. M. Fy, Department f Epidemilgy, (SC-36), Schl f Public Health and Cmmunity Medicine, University f Washingtn, Seattle, Washingtn we nw reprt a repeated infectin with M. pneumniae in a patient with humral immundeficiency. Patients and Methds Surveillance. Beginning in 1963, all cases f pneumnia that ccurred in the Grup Health Cperative f Puget Sund were recrded; thrat swabs and paired sera were cllected with the aid f physicians at the clinic [2, 3]. By 1975, M. pneumniae had been islated frm almst 1,000 patients. Half f these cases were diagnsed befre 1970, the year when the first recurrence f M. pneumniae pneumnia was recgnized. At the beginning f the study, thrat swabs were cllected frm --50CJ f the patients with pneumnia, and paired sera were taken frm 30%, but cllectin fell t abut 23% and 20%, respectively, during the 1970s. Decreased participatin in the study was due t the increased wrk lad f physicians, cmbined with the time-cnsuming prcedure f btaining written cnsent fr cllectin f specimens. Thus, the chance fr diagnsis f a repeated case f pneumnia was cmprmised by less than cmplete labratry investigatin f cases f pneumnia, as well as attritin frm the study ppulatin because f terminatin f membership in the Grup Health Plan. n additin, a large prprtin f the teenagers wh cntracted M. pneumniae pneumnia in the 1960s had left Seattle by the 197Os. Beginning in 1971, a special effrt was made t uncver recurrent pneumnia due t M. pneu- 673

2 674 Fay et al..;.s! <;) ;;<u l:: <;;.s <;) <.J :;;; :::l..:::: 0. a -l U ;;.. -'''' 0 en.0. * l:: B e 2 E5 'a u 8 '';:: C 8 -c C -<;: fr. <S J:l < E-< 0 1::?.S. t+-l._ c u.s u. <; u :5 ụ. ;;., S E :::l [J'1 c : -'.. l: 0 U en c. p. Q.>:! >: ;:. en en en en = c Q E N - <.O.. l!'> _OON V C Q,) '0 u C ;;.. C :.s,:0. -' 0 0 O'l c.. c 0> C. >: ' ' en a :.s ;;.. 0 ;;.. u u.. c..c c t: c t: E-<E-< u)f'..s en ''''' C<.O 0>.0 -:. 'g 0 Q) ' 0 0 ZZi:i: ZZ S a S :: -' > S z:e:e a>- :i C'.i e-r 00,00.. v ' 00 N,;l;.. cq''''''-.::t',i'''''..:;v,..:.:..:..;,..:.;v..,; c S. a..>l ;.t). :i e S c..>l ; 0>..,;,' ;;.. :g -' :E' <0. a. 0 2.! aene zzzz r-, 0 r-,.9 U C ;;.. :.::: a u 0 ;;.. ;;i..c.9 ;:.9.5 t- Q,) E c'aaci' :.::: 2 S2e::: -5 :g -5] es e e e s e e Z,Zf-< (l) O.J iu iu,,.ll,, _ 0 tl tl 0 tl tl - ; -t tl $-r $-r V -t iu O.J ; Ql tj,,) SSS6S tl<wo <::<t:..c..c:....c..c i2i2i23i2i2; <.O'<i'OO 00 (,Ol-t,O..-lt,O..-l cn;';'$-r'1-r- ex e ']] aaa2ca..c..,g,g,g,g f-< Z + c tj J., ::s 0.. c e f-< cz en c ::s en 0' en.0 a ;;.. C en 1:!..c en u..!: c c ;> ui u a S.... C en., <t:'';:: c bb 't-.5 C<fJ. a e en l.l 't- c t:: U (1]9 ;;.. u.. C c f-< 0 -;;...,.. ;> c... -'.Ll en., c v 0 u 8-5 'u '0 C 'c.. ::s 1;\ :;:;,.8 -'., - ::s u 'P;> ; c 0 00-' en Z. :...c!::.. ;:! C ;> ';,.. en -' t::.±..:: * +- mniae, Patients were asked by letter t remind their physicians abut previus episdes f infectin with M. pneumniae if they became ill again r t cntact us (the investigatrs) directly. Fllw-up bld specimens were slicited annually. slatin f rganisms and serlgy. The prcedure fr islatin and identificatin f M. pneumniae, with use f slid as well as diphasic medium, has been described [5, 6]. Antibdy t M. pneumniae was measured by CF tests with lipid antigen [5.6]. Patients. Table 1 summarizes the clinical findings f the six cases f repeated M. pneumniae pneumnia, including the patient with immundeficiency. All cases were verified by islatin f M. pneumniae frm thrat culture during bth episdes f illness. Attempts at recvery f the rganism a mnth r mre after the secnd episde were carried ut in fur cases and failed. Patient n. 1 was described previusly in detail [4]. Patient n. 2 was seven years ld at the first episde f verified M. pneumniae pneumnia in 1963 but had a histry f ne previus episde f pneumnia earlier in childhd. This case was described previusly as case n. 3 [1]. Antibitic treatment f this by was pstpned fr 12 days in 1963 because the illness was believed t have viral etilgy; prbably as a result f pstpnement, his illness was prtracted. The titer f CF antibdy was 1:256 n day 12 f illness and 1:128 n day 40. Serum btained in 1972 fr fllw-up study had a titer f <1 :2. The secnd episde f pneumnia ccurred in August 1974 when Seattle experienced an epidemic f pneumnia due t M. pneumniae. Patient n. 2 was treated with erythrmycin estlate (Eli Lilly and Cmpany. ndianaplis, nd.) fr six days and reprted subjective imprvement and cessatin f cugh after a week. Bth the patient and his mther characterized the episde f pneumnia in 1974 as milder than the ne in Hwever, it shuld be nted that specific antibitic therapy was instituted earlier in 1974 than in Patient n. 3 was an -year-ld girl wh had a thrat culture psitive fr M. pneumniae when examined in a neighbrhd investigatin cnducted by ur public health nurse f a mini-

3 Recurrence ] 11. pneumniae Pneumnia 67.5 epidemic f infectins due t M. pneumniae. The girl had experienced sre thrat, malaise, and a recurrent cugh but n fever. Upn reprt f the psitive culture, the patient was referred t the Grup Health clinic, and a chest film taken ne mnth after culture revealed a patchy infiltrate behind the heart. The titer f CF antibdy in cnvalescent-phase serum was 1:32; a fllw-up specimen btained in 1972 had a titer f < 1:2. The first illness was cnsidered t be mild, and n antibitics were given. The secnd episde f illness, which ccurred in 1974, was mre severe. The patient's temperature reached 39.7 C, and she was treated with tetracycline. Her titer f CF antibdy rse frm 1:8 t 1:64; by Nvember 1976 the titer had fallen t 1:8. Patients n. 4 and 5 were a brther and sister wh were bth diagnsed in Nvember 1968 as having pneumnia due t M. pneumniae. n the middle f February 1971, the by cntracted a febrile illness characterized by cugh, malaise, cryza, sre thrat, headache, nausea, and vmiting. He was nt examined until three weeks later. nfectin with M. pneumniae was suspected, and the family was investigated by ur public health nurse. This investigatin revealed that his sister (patient n. 5), wh develped mild respiratry illness three weeks after the nset f her brther's illness, als had M. pneurnniae in the thrat. A chest film, nt taken until May, shwed a minimal infiltrate at the base f the right lung. N treatment was given. Bth brther and sister had titers f CF antibdy f 1: 16 in their cnvalescent-phase sera; their titers f antibdy had fallen t <1:2 by Octber Thrat cultures and sera were cllected in March and April f 1971 frm bth parents and frm tw additinal siblings 15 and 17 years ld. These cultures were all negative. The parents' sera lacked detectable CF antibdies, but the tw siblings had titers f CF antibdy f 1:16 and 1:32, respectively, The 15-year-ld sister develped a rash at the time that her yunger sibling had a respiratry illness. Review f the recrds revealed that neither the parents nr the tw lder siblings had sught medical care fr respiratry disease when they were expsed t M. pneumniae in Patient n. 6 was a 19-year-ld male with a variable immundeficiency syndrme invlving bne marrw-derived (B-) cells nly (hypgammaglbulinemia). He cntracted an infectin due t M. pneumniae characterized by severe cugh and fever in January This cmplicated case was reprted previusly as case n. 4 [7]. Thrat culture was psitive fr M. pneumniae in J anuary f 1972 but was negative when repeated in February and April f One year after his first dcumented M. pneumniae infectin, patient n. 6 returned fr a rutine visit, at which time he cmplained f cugh and fever. The latter symptms were similar t but milder than thse f January Rhnchi were heard in the chest bilaterally, but a chest film was nt taken. A thrat swab was again psitive fr M. pneumniae. The patient, wh was being treated with weekly injectins f gammaglbulin, had nt btained his regular dsage fr three weeks. He was given 30 ml f gammaglbulin im and 500 mg f tetracycline three times daily n an ambulatry basis, and he prmptly recvered. Subsequent rutine thrat cultures btained in June 1973 and January 1975 were negative fr M. pneumniae. Since the patient was knwn nt t prduce measurable levels f antibdy, serlgic tests were mitted during the secnd episde f illness. Estimatin f the prbability f encuntering repeated cases f M. pneumniae pneumnia. The verall incidence f M. pneumniae pneumnia during the study perid was 1.7 cases per 1,000 members f the Grup Health Plan [3]. We calculated the number f patients wh had had M. pneumniae pneumnia three r mre years previusly and were still members f the Grup Health Plan fr each year f fllw-up study frm 1971 t 1975 (after the first repeated case was recgnized). Altgether, 393, '119,418,417, and 495 such frmer patients were under bservatin fr each f these years, respectively, fr a ttal f 2,142 persn-years f risk. Thus, the rate f recurrent M. pneumniae pneumnia with a lapse f three r mre years between episdes was fur cases per 2,142 persns r 1.9 episdes per 1,000 persns per year. This rate is remarkably similar t the verall incidence in the Grup Health Cperative (1.7 cases per 1,000 persns). Questinnaires and hspital recrds suggest that eight additinal cases f repeated pneumnia ccurred in this risk grup, but we did nt

4 676 Fv et al. receive diagnstic specimens. Thus, the incidence f repeated M. pneumniae pneumnia may have been greater than what was demnstrated. Six patients previusly infected with M. pneumniae had secnd attacks f pneumnia shwn nt t be due t M. pneumniae. Discussin Althugh the number f dcumented cases f repeated M. pneumniae pneumnia are few at this time, the data suggest that M. pneumniae pneumnia ccurs as frequently in patients frmerly infected with M, pneumniae as in the general ppulatin, at least after a time lapse f apprximately three t five years. We d nt knw hw many f the infectins in the general ppulatin are primary infectins r reinfectins [2]. Furthermre, it is pssible that the persns identified as having repeated pneumnias are prne t reinfectin fr sme immunlgical r physilgical reasn. At present, we interpret these data t indicate that naturally acquired immunity t M. pneumniae pneumnia is nt durable, althugh we cannt exclude the pssibility that the persns with reinfectins represent a subset f the ppulatin. The fact that during epidemics the prprtinal increase in incidence is highest amng teenagers [2] suggests that this age grup is at special risk f reinfectin; five f ur six reinfectins ccurred in this age grup. The patients were nt likely t have chrnic infectins since levels f humral antibdy fell between and after infectins, and the rganism culd nt be islated after acute illness. Tw f the repeated cases f M. pneumniae pneumnia (patients n. 2 and 3) ccurred during an epidemic in 1974, and a pair f siblings (patients n. 4 and 5) became ill and had a cmpatible incubatin perid; these circumstances suggest that the secnd episdes f illness were acquired thrugh persn-t-persn transmissin. We did nt bserve a clear tendency t mre severe r milder disease during the secnd infectin; the secnd attack f illness appeared milder in three cases and mre severe in the ther three. n three cases the secnd episde affected the ppsite lung as in the first episde, and in tw cases the same side and general area were affected. Serlgic evidence f repeated infectin due t M. pneumniae has been reprted, but data n clinical manifestatins f such infectins are lacking [8-12]. Mst studies suggest that the presence f antibdies is assciated with prtectin r mdificatin f clinical manifestatins [8, 10]. We previusly reprted that manifestatins f infectin with M. pneumniae in patients with deficiency f the humral immune system were prtracted and severe [7]. One f these patients with immundeficiency acquired M. pneumniae infectin again after nly ne year, an ccurrence which suggested that humral antibdies are imprtant in resistance t this rganism. Lng-term serlgic studies suggest that humral antibdies wane after tw t five years, whereas cell-mediated immunity may persist lnger [6, 13-17]. The duratin f humral antibdies rughly parallels the interval f tw and ne-half t 10 years that was bserved between repeated infectins. Epidemics f infectin due t M. pneumniae may ccur in cycles f fur t five years [18]. n Seattle the cycle has been lnger; a majr epidemic ccurred ver 14 mnths in and peaked in January f A slight rise in incidence was bserved in , but the secnd majr epidemic peaked in the late summer f 1974 [18]. t is pssible that the cyclicity f M. pneumniae infectin may be explained in part by the waning f immunity amng the ppulatin. The present findings have ramificatins fr the develpment f vaccines. Killed M. pneumniae vaccines have been shwn t prtect against pneumnia due t this rganism, at least temprarily [18]. A vaccine may have t be mre immungenic than natural infectin t induce a durable immunity, r vaccines wuld have t be given at the nset f each epidemic. References l. Graystn, J. T., Alexander, E. R., Kenny, G. E., Clarke, E. R., Fremnt, J. C., MacCall, W. A. Mycplasma pneumniae infectins, J.A.M.A. 191: , Fy, H. M., Kenny, G. E., McMahan, R., Mansy, A. M.,

5 Recurrence f M. pneumniae Pneumnia 677 Craystn, J. T. Mycplasma pneumniae pneumnia in an urban area. JA.M.A. 214: , Fy, H. M., Cney, M. K., McMahan, R., Graystn, J.T. Viral and mycplasmal pneumnia in a prepaid medical care grup during an eight-year perid. Am. J. Epidemil. 97:93-102, Fy, H. M., Nugent, C. G., Kenny, G. E., McMahan, R., Graystn, J. T. Repeated Mycplasma pneumniae pneumnia after 4 years. J.A.M.A. 216: , Kenny, G. E. Mycplasms. n E. H. Lennette [ed.]. Manual f clinical micrbilgy. 2nd ed. American Sciety fr Micrbilgy, Washingtn, D.C., 1974, p Craystn, J. T., Fy, H. M., Kenny, G. E. The epidemilgy f mycplasma infectins f the human respiratry tract. n L. Hayflick [ed.], The mycplasmatales and the.-phase f bacteria. Appletn Century Crfts, New Yrk, 1969, p Fy, H. M., Ochs, H., Davis, S. D., Kenny, G. E., Luce, R. R. Mycplasma pneumniae infectins in patients with immundeficiency syndrmes: reprt f fur cases. J. nfect. Dis. 127: , Steinberg, P., White, R. J.,Fuld, S. L., Gutekunst, R. R., Chanck, R. M., Senterfit, R. M. Eclgy f Mycplasma pneumniae infectins in marine recruits at Parris sland, Suth Carlina. Am. J. Epidemi. 89: 62-73, Saliba, G. S., Glezen, W. P., Chin, T. D. Y. Mycplasma pneumniae infectin in a resident bys' hme. Am. J. Epidemil. 86: , Dwdle, W. R., Stewart, J A., Heyward, J. T., Rbinsn, R. Q. Mycplasma pneumniae infectins in a children's ppulatin: a five-year study. Am. J. Epidemil. 85: , Evans, A. S. Serlgic studies f acute respiratry infectins in military persnnel. Yale J. Bi. Med. 48: , Cney, M. K., Fx, J. P., Hall, C. E. The Seattle virus watch. V. Observatins f infectins with an illness due t parainfluenza, mumps and respiratry syncytia1 viruses and Mycplasma pneumniae. Am. J. Epidemil. 101: , rder, L., Flrey, C. D. V., Hrstmann, D. M. Persistence f antibdies t Mycplasma pneumniae fllwing naturally-acquired infectins. Am. J. Epidemil. 88: , Biberfcld, G. Antibdy respnses in Mycplasma [meumniae infectin in relatin t serum immunglbulins, especially gm. Acta Path. Micrbil. Scand. [B] 79: , Biberfe1d, G. Cell-mediated immune respnse fllwing Mycplasma pneumniae infectin in man.. Leuccyte migratin inhibitin. Clin. Exp, mmunl. 17:43-49, Fernald, G. W. n vitr respnse f human lymphcytes t Mycplasm pneumniae. nfec. mmun. 5: , Biberfeld, G., Biberfeld, P., Sterner, G. Cell-mediated immune respnse fllwing Mycplasma pneumniae infectin in man.. Lymphcyte stimulatin. Clin. Exp. mmunl. 17:29--41, Fy, H. M. Mycplasma pneumniae pneumnia. n P. F. Wehrle and F. H. Tp [ed.]. Cmmunicable and infectius diseases. 8th ed. C. V. Msby Cmpany, St. Luis, 1976, p