Hospital Practice
ISSN: 2154-8331 (Print) 2377-1003 (Online) Journal homepage: http://www.tandfonline.com/loi/ihop20
Chlamydial Genital Infections: A Growing Problem King K. Holmes & Walter E. Stamm To cite this article: King K. Holmes & Walter E. Stamm (1979) Chlamydial Genital Infections: A Growing Problem, Hospital Practice, 14:10, 105-117, DOI: 10.1080/21548331.1979.11707630 To link to this article: http://dx.doi.org/10.1080/21548331.1979.11707630
Published online: 06 Jul 2016.
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Date: 19 August 2017, At: 03:58
Chlamydia! Gecital Infections: A Growing Problem
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KIN
a
K. H OLMES and WALTER
E. STA MM
Uniuerstty of Washington
As a cause of urethritls, acute epldidymtUs. pelvic tnflammatory disease, and their complications, Chlamydia trachomatts ts rapidly outstrtpptng N. gonorrhoeae. Slgns and symptoms of chlamydiallnfecttons resemble those of gonorrhea, and rolnfectlon ts common, but treatment may be approprlate for gonococci but not chlamydiae. Guidelines are offered for diagnosls and effective treatment.
Although genital tract Infections wlth Chlamydia trachomatts have been recognlzed slnce the beglnnlng of this century, the organlsm was not consldered a major cause of sexually transmltted dlsease untll recently. Durlng the last decade. however. several studles have produced evidence that C. trachomatts causes both nongonococcal urethrltls ln men and pelvtc lnflammatory dlsease ln women. In fact. morbldlty from chlamydlal genital tract Infection ln this country now rivais and may exceed that from gonorrhea. Dependlng upon the population studled. more than half the cases of acute urethrltls are nongonococcal. and among certain groups. partlcularly male college students. 80% to 90% are nongonococcal. C. trachomatls causes 30% to 50% of these cases of nongonococcal urethrttls. ln addition. between one thlrd and two thlrds of men treated effectlvely wlth penlclllln or spectlnomycln for uncompllcated gonorrhea develop postgonococcal urethrltls. There ls strong evtdence that at !east half of these cases are due to slmultaneous acquisition of chlamydtal and gonococèal Infections. Our studles. as weil as thO!~e of J. D. Oriel ln England. have shown that men wlth laboratory-proved mlxed Nelsserta gonorrhoeae and C. trachomatls urethritls almost lnvarlably develop postgonococcal urethritls after penlcillin therapy for gonorrhea. From what ls known of the pecullar ltfe cycle of chlamydiae. descrlbed ln a prevtous article by E. R. Alexander (see "Chlamydia: The Organism and Neonatal Infection," HP. July 1979). lt ls probable that C. trachomatls has a longer Incubation perlod than N. gonorrhoeae and therefore does not cause symptoms of urethrltls untll two to three weeks after antlblotlc treatment for gonorrhea. Noteworthy ln this regard ts the fact that of the treatment regtmens for gonorrhea recommended by the Center for Disease Control. only one the
tetracycline regi men - ts effective agatnst chlamydlae. Treatment of gonorrhea wlth penlcllltn G. amplclllln. or specttnomycln will eradtcate N. gonorrhoeae but not C. trachomatls. The dtagnosts of nongonococcal urethrttls cannot be made solely on cllnlcal grounds. The slgns and symptoms are slmllar to those of gonorrhea. tncludtng meatal erythema and tenderness. urethral discharge, dysurla. or urethral ltchlng. ln general. however. nongonococcal urethrltts ls Jess severe than gonorrhea. and a substantlal proportion of men wtth proved C. trachomatls Infection of the urethra have no overt slgns and symptoms of urethritls. ln practtce, the dtagnosls of nongonococcal urethrltls ls usually made on the basts of an overt leukocytlc urethral exudate on physical examtnatlon and the absence of N. gonorrhoeae on a gram staln of the exudate. Subsequent cultures also should be negative for gonococcl. To make a presumptlve dlagnosis of nongonococcal urethritls ln the absence of overt urethral exudate. one should examine a specimen of urethral secretions obtalned wlth a small endourethral swab. A gram stain of the specimen ls flrst scanned at law power to ldenttfy areas of the sllde contalnlng maxImal concentrations of leukocytes. These areas are then examlned under oll Immersion. An average of four or more leukocytes per l.OOOX field ln at !east three of flve fields indicates urethritts and also correlaies wlth recovery of C. trachomatls. Alternatlvely. the
Dr. Holme11 111 Profellsor of Medldne. University of WtUblngton.
and Cblef, Division of lnfectlow DlletUn, U.S. Public Healtb Service Ho1pltal, Seattle. Dr. Stamm ls A11lstant Profnsor of Medldne, University of WtUblngton. and Codi!Yctor, Harborvlrw Medical Center Sexually Transmllled Dlsea~~e Cllnlc, Seattle. Hospital Practtce October 1979
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demonstration of pyurta, deflned as 15 or more leukocytes per 400X microscopie field. ln the sediment of flrst-votded early-morntng urine alsa provldes presumptive evidence of C. trachomatts Infection ln asymptomatlc or symptomatic men wtth a htstory of exposure to sex partners wlth nongonococcal salptngttis or mucopurulent cervlcltis, and ln fathers of chlldren wtth Inclusion conjunctivltis. Unfortunately, Gtemsa-statned or lmmunofluorescent smears of urethral exudate are tnsensttive ln the specifie dtagnosts of chlamydtal genital tract Infections. A specifie etiologie dtagnosts ts therefore not routinely sought ln patients wtth nongonococcal urethrttis. Dlfferentiation of the 40% to 50% of cases caused by C. trachomatts from the remalntng Idiopathie cases depends on Isolation of C. trachomatts ln tissue cell culture or on serologie evidence of Infection. Bath procedures are dlfflcult to perform and nelther ts readlly avallable. although most vlrology laboratortes can perform tissue culture Isolation of C. trachomatts. To obtaln an adequate specimen tt ls necessary to tnsert an endothelial swab 1 to 2 cm tnto the urethra. The specimen should be placed ln a transport medium contatnlng pentctllln and streptomyctn and sent to a vlrology laboratory for culture. A mtcrolmmunofluorescence test ustng C. trachomatts antigens. developed by S.-P. Wang and J. T. Grayston at the University of WashIngton, measures antibodles by lmmunotype spectflclty and by tmmunoglobln class ln bath serum and local secretions. Although tt bas been greatly slmpllfted, tt still ts avallable only ln research laboratortes; tt ts as dtfftcult to perform as Nongonococcal uretbritis can oflen be distissue culture and requtres demonttngulshed from gonococcal by appearance of uretbral gram stain. Normal smear (top) stration of lgM antlbody or a fourshows no polymorpbonuclear leukocytes, fold rtse ln anttbody titer ln patred many transitlonal epithelial cells, occa· sera to dtfferentiate current from sional mononuclear cells, and noncellular past Infection. Studles by Grayston debris. ln nongonococcal urelbrltts, smear and Wang of C. trachomatts ocular (center) shows polymorphonuclear leukoInfection ln the monkey madel cytes and mononuclear lnjlammatory cells, showed that lgM lmmunofluoresbut no gonococcl. Gonococcal uretbrllis cent an tl body was demonstrable afsmear (bottom) shows many polymorphoter prtmary Inoculation but not after nuclear leulwcytes, sorne with gram-negarepeat challenge wlth the same tmtive lntracellular diplococcl ( GNID). 106
Hospital Practlce October 1979
munotype. Our cllnlcal experience supports thetr flndtng that lgM antibody or seroconverston tndtcates recent Infection. However, patients wlth mlld Infections often do not seek treatment untillt ts tao late to demonstrate a rtse ln antlbody tlter ln patred sera, and tt may not be possible to demonstrate IgM antibody ln a pattent who prevtously bas been tnfected wtth the same lmmunotype. For these reasons. serologie tests may not dtfferenttate past from current Infection. The recognlzed complications of chlamydia! urethrltis ln men are epldldymttis and posstbly arthrttts (Retter's dtsease). Epldtdymttls may also result from gonorrhea and from collform or pseudomonas urtnary tract Infection, but ln recent years the majortty of cases have been categortzed as "idiopathie," stnce a causative organtsm often cannat be found. Idiopathie eptdldymttis bas been attrtbuted to chemtcal Inflammation caused by reflux of sterile urine down the vas deferens, but the condition ts most frequently dtagnosed ln young men wtth a hlstory of nongonococcal urethrttis. We have found evidence of C. trachomatls Infection ln association wtth most acute eptdtdymttis ln young men. In our study of 50 men wtth acute epldldymltis, C. trachomatls was demonstrated by Isolation of the organlsm or by a rtse ln mtcrotmmunofluorescent antibody tlter ln 17 of the 34 who were under 35 and ln none of the 16 men over 35 years of age. ln the younger group. the organlsm was found ln 16 of 24 who bad no other pathogen recovered and no his tory of sc rotai trauma and wh ose condition ln the past would have been termed Idiopathie epldtdymttis; ln flve of stx such patients ln whom eptdtdymal aspiration was done, C. trachomatts was lsolated dtrectly from the asptrates. Only seven men, ali under 35, bad gonorrhea. Coltform or pseudomonas organtsms were tsolated from 12 of the 16 men ln the older group but from only one of the 34 ln the younger group. These results tndtcate that acute epldldymltis ln men under age 35 ts usually caused by
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C. trachomatts or N. gonorrhoeae, whlle Infection wtth coltform bacterta ts the most frequent cause ln older men. Certain cltnlcat and epidemiologie features help to dtstlngulsh chlamydia! eptdldymttts from that due to coltform Infection. A htstory of recent sexual exposure was more common among those wtth chlamydlal or gonococcallnfectlon than among those wtth coltform Infection. On examlnatlon. urethral discharge could be expressed from 11 of 17 men wtth chlamydtal eptdtd-
ymltts. seven of seven wtth gonococcal urethrttts, but only three of 13 wtth coltform or pseudomonas Infection and three of 13 who had no deftnlte pathogen recovered. Thus. age. recent sexual exposure, and presence of urethrttls help to dlsttngulsh men wtth chlamydtal or gonococcal eptdldymttts from those wtth epldldymltls of other etiologies. Among men wtth acute epldldymltls who have demonstrable urethral exudate. a gram-stalned smear and culture may reveat N. gonorrhoeae. A presumptlve dlagnosts of chia-
mydtal eptdtdymltls ls warranted ln those who have urethral dlscharge but negative tests for gonorrhea. Although chlamydia! epldldymltls may not be assoclated wtth acute urethrltts, the major diagnoses to conslder ln young men wlth acute testtcular swelllng and/or pain are torsion. whlch should be ruled out by Doppler flow studles; radionuclide scan or surglcal exploration; direct trauma to the scrotal contents; and tumor or tuberculosls, whlch are suggested by fallure to lmprove wtth tetracycltne therapy. Hoepltal Practtœ October 1979
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A cu te epididymitis is often diagnosed as idiopathie, but culture of 11rlne or materlal from genital sites rer•ealed Infection in the majorlty of the 50 patients studied. C. trachomatis was iso/ated more frequent/y from men under 3'5 years of age, coliform organisms and Psmdomonas more often from those or•er 3 5. A mong tbose in yormger age group, er•ldence of C. trachomatis infection also u•as fou nd, by l$olation or serocom•erslon. ln one patient witb N. gonorrhoeae and one with idiopathie epididymitis, respectlr•ely.
The most serlous condition that often arises as a complication of nongonococcal urethrltls ls Relter's dlsease. It reportedly occurs ln fewer than 1% of patients wlth urethrttls, but lt can be serlous and chronlcally debilltatlng, lnvolving the eyes, Joints, skln, and mucous membranes. Symptoms usually appear one to four weeks after onset of urethrltls. Ocular symptoms range from mlld translent conJunctlvitls to severe uveltls, whlch frequently relapses and may result ln bllndness. The arthrltls ls usually asymmetrlc and affects the large Joints of the lower extremltles or the sacroillac Joints, Achilles tendons, and plantar fasclae (see R. Bluestone, "The Seronegative Spondylarthropathles, page 87 ). The Initial episode may be dlsabllng and often lasts for several months. Eventually the symptoms remit spontaneously, but recurrences are corn mon. The dermatologie manifestations of Relter's dlsease lnclude balanltls clrclnata; keratoderma blennorrhaglca lnvolving the soles of the feet and, ln sorne cases, the palms 108
Hospital Practlce October 1979
of the hands or other parts of the body: and small superflclal ulcers of the palate, tongue, and oral mucosa. Although the penlle and sktn lesions look qulte dramatlc, they are usually palnless. Among men wlth untreated acute Reiter's dlsease, Hausa et al demonstrated C. trachomatls urethral Infection ln two thlrds of those wlth urethrltls. We have lsolated C. trachomatls from a slmilar proportion of patients with acute urethrltls and Relter's dlsease, as weil as from thelr sex partners. Therefore, treatment wlth tetracycline Js advisable for both pattent and sex partner. Antiblotic therapy may cure the underlylng Infection, but there ls no known cure for Reiter's dlsease. There ts strong evidence that Relter's dlsease has a genette basls. Over a decade ago, G. W. Csonka noted a famlllal tendency, and R. Morris and assoclates subsequently found that 96% of thelr patients wlth Relter's dlsease possessed the HLA-B27 hlstocompatiblllty antigen. compared with only 8% of a control group. Other studles have shown a relationshlp
between Relter's dlsease, ankyIoslng spondylltls, and the HLA-B27 antlgen. Although 1t has not been proved, it appears possible that ln genetlcally susceptible lndlviduals, Infection wlth the causative agent of nongonococcal urethrttls lnltlates the manifestations of the dlsease. The drug of cholce ln treatlng nongonococcal urethrltls ls tetracycline hydrochlorlde. The treatment reg! men recommended by the Center for Dlsease Control ls 500 mg qtd for seven days. Alternative tetracycline reglmens that can be used lnclude doxycycline, 100 mg btd for seven days. However, we believe 100 mg once dally for seven days may be Just as effective. Nearly every pattent wlth nongonococcal urethrltls lmproves on this regimen, although many continue to have a clear mucold urethral discharge, whlch eventually resolves after treatment ls completed. Since no tetracycline-resistant stralns of C. trachomatts are known, failure to show lmprovement on tetracycline therapy suggests that the patient ls not complylng, that the dlagnosls should be reevaluated, or that Infection may be due to a mlcroorganlsm other than C. trachomatls. It ls known, for example, that about 10% of stralns of Ureaplasma urealyttcum, a genital mycoplasma that probably causes sorne cases of nongonococcal urethrltls, are htghly resistant to tetracycline hydrochlorlde. Erythromycln base ls effective agalnst C. trachomatls and moderately effective agalnst U. urealyttcum ln vitro, and lt cao be used ln the same dosage, 500 mg qld for 14 days, ln patients who do not lmprove on tetracycline. It ls also essential to offer treatment wlth tetracycline or erythromycln to the patlent's sex partner. When a patient falls to respond to elther of the treatments suggested above, other diagnoses to conslder lnclude urethrallnfectlon with herpes slmplex virus or Trichomonas vagtnalls, persistent Infection of the perturethral glands or prostate, or anatomie abnormalltJes of the urethra, such as a strtcture. In most cases of herpesvtrus Infection, charactertstic herpetlc penlle lesions are
can be dlagnosed by examlnlng the sediment of flrst-voided urine. The diagnosls of prostatltls can be establlshed uslng the flve-glass collection technique of Stamey and coworkers. Urethroscopy may be necessary to assess the posslblllty of urethra.l anatomie abnormall.tles. Although perststence of urethrltls wlthout improvement ls uncommon durlng tetracycline therapy of nongonococcal urethritls. recurrence of urethrltls wlthln two to six
weeks after therapy is common and presents the major therapeutlc dllemma. In our recent experience, 47% of men wlth chlamydia-negative nongonococcal urethrltls have perslstence of the condition or. more often, recurrence wlthln six weeks after tetracycline therapy. In contrast, only 17% of men wlth urethrltls due to C. trachomatts have recurrent nongonococcal urethrltls wlthln six weeks after tetracycline treatment. and this organlsm usu-
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present, but ln an occaslonal patient these lesions may be lnslgnlflcant or absent. In such cases. the presence of tender Inguinal adenopathy and/or an area of focal tenderness noted on urethral palpation suggest herpetlc urethrltls, provtdlng gonorrhea deflnltely has been ruled out. T. vagtnalts Infection, an uncommon cause of nongonococcal urethrltls, should be considered only when a patient falls to respond to tetracycline. It
Hospital Practlce October 1979
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Manifestations of Reilt.,.'s diseme lm·lude mymmetrlc sU'elllnl( atld Inflammation of tbt• jolrlls, as shou•n ln tbt• photol(rapb (top lefi) and tbt.,.,WJ(ram from patient u•llb foot fulltl und llt'J(atit't' .'1:-ravs ( hollom ). and skln /t>sllms, su ch as kt.,.atodt.,.ma hlennorrbal(kum of the solt•s of lbt• ft•t•t (top rll(bt ). C. rrachomaris bas heen l.wlalt•d from tu•o tblrds of lht• patit•nt.r u1tb Rt•llt.,.'s dlsra.w, oaurrlnl( as a sequt'la of nonl(onococctll un•thrltls. ( 7bt.,.,WJ(ram and photo, top rll(bl, murtesv of Dr. Rotlm')•IJiurstone.)
l l0
Hospital Practtce October 1979
ally cannot be retsolated from such patients. Wtth more prolonged foiJow-up, however, chlamydia-positive recurrences are occastonally seen. Stnce latency ts an Important aspect of chlamydia! Infection, tt ts dtfftcult to know whether these late recurrences represent relapse or retnfectton wlth C. trachomatts. The organtsm has a two-phase llfe cycle, exlsttng as an extracellular nonrepllcattng form capable of lnfectlng host cells and as a nonlnfectlous obllgate lntracellular replicattng form. lt may survive as an lntracellular parasite even whlle lts multiplication ls held ln check by host defense mechanlsms. Bath c. pstttact and C. trachomatts stralns are known to cause relapslng discase many years after the original Infection. For Instance, treatment wlth cortisone eye olntment can reacttvate acute trachoma ln a pattent wlth long-dormant eye infection. On the other hand, as wlth any sexually transmttted dlsease, the late-recurrence rate of chlamydia) genital Infections may be attrtbutable to relnfection. Optimal therapy for carly recurrence of nongonococcal urethritl" after Initial lmprovement on tetracycline has not yet been weil deflned. One can glve a prolonged course of treatment wlth tetracycline (e.g., 500 mg btd for 30 days) and make certain the sex partner recetves stmultaneous treatment. Men who have had carly recurrence after treatment may be encouraged to use a condom durtng Intercourse for at !east two months, whlch will help dtffcrentlate relapse from relnfecUon ln any subsequent recurrence. Alternative treatment reglmens for patients wlth carly recurrence lnelude erythromycln, 500 mg qid for 14 days, or sulflsoxazole, 500 mg q 1d for 10 days. Penlcllll n and amplclllln are much Jess effective than tetracycline or erythromycln agalnst chlamydial Infection and are of little or no value ln nongonococcal urethrltls. Most regimens recommcnded for the treatment of syphilis and gonorrhea, cxcept the tetracycline reglmen, are not effective agalnst chlamydlal genl(contlnued on page 115)
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CHLAMYOIAL
(from page 110)
tai tract Infections, and C. trachomatts ts not reltably eradtcated by stngle-dose therapy wtth any antlmtcroblal. The optimal treatment for chlamydlal eptdldymttis ts tetracycline. 500 mg q t d for 10 days. Genital C. trachomatts Infections, like genital N. gonorrhoeae Infections, produce even more morbldlty ln women than ln men. C. trachomatts has been lsolated from the cervtx of 20% to 60% of women wlth gonorrhea or a hlstory of contact wlth gonorrhea. ln women wtthout gonorrhea, chlamydtae have been tsolated from the cervtx ln 10% to 20% of females seen ln
VD cltntcs and ln about 5% of those attendlng gynecology or prenatal clinlcs. ln prenatal clinlcs servtng Indigent populations. up to 25% of pregnant women have bad C. trachomatts Infection of the cervtx. These flndlngs lndlcate that mlxed gonorrheal and chlamydlal Infections frequently are present ln women as well as ln men, partlcularly ln the young. sexually active patient population seen ln VD clinlcs. The symptoms and stgns of C. trachomatts genital tract Infections ln women resemble those of gonorrhea and, as wtth gonorrhea ln women. may be mtld enough to be tgnored or may be entlrely absent.
Both gonorrhea and chlamydlal Infection may cause a mucopurulent cervical exudate, usually assoclated wlth erythema. edema. congestion. and lncreased frtabtltty of the cervtx. Cervtcltis due to herpes slmplex virus Infection can be confused wtth gonorrhea or chlamydlal cervtcttts. but lt usually causes Inflammation and ulceration of both the exocervtx and endocervtx rather than the endocervtx alone. ln Seattle. N. gonorrhoeae has been recovered from the cervtx ln 50% of women wtth pelvtc tnflammatory dlsease. C. trachomatts bas been tsolated from the cervtx ln 20%. whtle another 10% of patients show an antibody response to tt.
Tr~atm~nt results i_n the National Gonorrhea Therapy Monitoring Study probably represent minimum estimates of efficacy since remfect1ons were mcluded as treatment failures. Data from N EngiJ Med 294:1, 1976
Hospital Practtce October 1979
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Thus, C. trachomatis may be lnvolved ln about 30% of the pelvtc lnflammatory dlsease seen ln Seattle. Mlxed infections wtth N. gonorrhoeae and C. trachomatts are commonly found in pelvtc inflammatory dlsease, making tt difflcult ln sorne cases to know which organlsm ls responslble for the Infection. Recent reports from Sweden suggest that C. trachomatts has become the main cause of pelvtc lnflammatory dlsease there (N. gonorrhoeae ls lsolated ln only 10% to 20% of cases. whereas at least 30% may be due to C. trachomatts). ln one study. C. trachomatts was isolated from the cervlx ln 19 of 53 women wlth acute salplngltls vertfied by laparoscopy and was recovered from the falloplan tubes, ln the absence of other pathogens, ln six of seven patients who had C. trachomatts ln the cervtx. ln addition, hlgh tlters of serum antlbody to C. trachomatts, often wtth three- or fourfold changes ln ttter, have been demonstrated ln an even hlgher percentage of pelvtc lnflammatory disease cases ln another Swedlsh study. lgM antlbody to C. trachomatts has also been demonstrated ln the majortty of women wtth acute perltonttls and/or perlhepatltis (Fitz-Hugh-Curtis syndrome) ln two recent studles. As noted prevtously, the presence of IgM anttbody lndicates recent C. trachomatts Infection. These data suggest C. trachomatts may cause sorne cases of acute perlhepatitts, whlch formerly had been attrlbuted excluslvely to N. gonorrhoeae. C. trachomatts has also been tsolated from Bartholln's duct ln patients wlth barthollnttls and from the rectum of women wlth C. trachomatts cervical Infection. Recent data suggest C. trachomatis can be recovered from the female urethra almost as often as from the cervtx and may be a cause of the urethral syndrome (dysurla and freq uency wtthout slgnlflcant bacterturla). Besldes caustng morbldlty ln adult women, C. trachomatts genital tract Infections carry the rtsk of perinatal transmission of Infection to the neonate. Inclusion conjunc116
Hospital Practlce October 1979
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Uvttts and an afebrtle pneumonla ln Infants, revlewed by Alexander, are now recognlzed consequences of maternai chlamydlal genital tract Infections. Maternai C. trachomatls Infection durlng pregnancy also bas been recently lmpllcated as a possible cause of fetal wastage and neonatal death and bas been assoclated wlth a hlgh rlsk of postpartum endometrltls and salplngltls. U ls not clear at present whether these perinatal and postpartum complications are dlrectly attrlbutable to C. trachomatls, and tt ls premature to recommend rouUne screenlng ln ali pregnant women. Conflrmatory studles are requlred. However, tt ls especlally Important to detect and treal chlamydia) genital Infections ln women ln certain other situations. Definitive dlagnosls of cervlcltls due to C. trachomatts depends on Isolation of the organlsm from an endocervlcal swab lnoculated lnto tissue culture ln a vlrology laboratory. ln practice, however, the presence of mucopurulent endocervlcltis suggests elther chlamydlal or gonococcal Infection. If tests for gonorrhea are negative, the patient "'h'luld be treated wlth letracycllne or erythromycln for presumed chlamydlallnfectlon, and male sex partners should be examlned for nongonococcal urethrltls. Simllarly, ali women who are recent sex partners of men wtth nongonococcal urethrttts (I.e., wlthln six weeks before onset of symptoms ln the male) should recelve approprlate therapy. The treatment for cervical chlamydlal Infection ls tetracycllne hydrochlorlde, 500 mg qld for seven days. For pregnant patients, erythromycln base, 500 mg btd for 14 days, should be used. Both regimens eradlcate C. trachomatts from the cervlx. For salplngltls, prellmlnary evidence lndlcates that tetracycline hydrochlorlde, 500 mg qtd for 10 days. produces cllnlcal and microbiologie cure. Studles currently are ln progress to determine what proportion of young women wtth the urethral syndrome have chlamydlallnfectlon, and whether such patients beneflt from antlmlcroblal therapy.
lntracellular chlamydia/ Inclusion bodies ( anou•) apparent ln cervical blopsy specimen are diagnostic of cblamydlal cervldtls but are rare/y seen ln endocenlfcal swab samples. Deflnltlr'e dlagnosls usually requlres Isolation ln tissue culture.
Slnce C. trachomatts Infections are more than twlce as common as gonorrhea. the morbldlty from chlamydlal genital tract dlsease ls rapldly outstrlpplng that of gonorrhea. The lncreased Incidence of genital chlamydia) Infections undoubtedly ls related ln part to changes ln sexual behavlor but has also resulted from the fact that little or no effort ls belng made to trace and treat sex partners of lndlvlduals wlth proved Infection or to detect asymptomatic lndlvtduals. ln contrast, these measures have been relatlvely effective ln the control of gonorrhea, partlcularly ln populations that have made good use of such control measures. Chlamydlal genital tract Infections have been
weil documented ln the sex partners of patients wlth nongonococcal urethrltls or endocervlcltls. The current situation wlth asymptomatlc chlamydlal genital tract Infections ls analogous to the probJem of asymptomatlc gonococcallnfectlon ln the sex partners of patients wtth gonorrhea. Chlamydlal genital tract Infections pose an addltlonal problem, however, both because they are more common and because facllltles for the specifie dlagnosls of C. trachomatls are not readlly avallable. 1t seems advlsable, therefore, to treat patients wtth cllnlcal slgns and symptoms of chlamydlal Infection wtth an effective antlblotlc regi men and to offer slmllar treatment to thelr partners. o
Selected Reading Holmes KK et al: Etlology of nongonococcal urethrttls. N Engl J Med 292:1199, 1975 Bowte WR et al: Etlology of nongonococcal urethrttla: EVidence for ChlamJ1dla tmchomatfs and Ureaplaama ureal11ttcum. J Clin ln\'est 59:735, 1977 Schachter J: Chlamydlallnfectlona. N Engt J Med 298:428. 490, 1978 Holmes KK. Hobson D (Edal: Nongonococcal Urethrttls and Related Infections. Amertcan Society for Mlcroblology, Waahlngton, DC. 1977 Berger RE et al: Etlology, manlfeatattons. and therapy of acute epldldymltls: Prospectt\'e atudy of 50 eues. J Urol 121:750, 1979 Kousa M. Salkku P. Richmond S, Lassus A: Frequent association of chlamydia Infection wtth Reiter'• syndrome. Sex Transm Dia 5:57, 1978
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ISSN: 2154-8331 (Print) 2377-1003 (Online) Journal homepage: http://www.tandfonline.com/loi/ihop20
Chlamydial Genital Infections: A Growing Problem King K. Holmes & Walter E. Stamm To cite this article: King K. Holmes & Walter E. Stamm (1979) Chlamydial Genital Infections: A Growing Problem, Hospital Practice, 14:10, 105-117, DOI: 10.1080/21548331.1979.11707630 To link to this article: http://dx.doi.org/10.1080/21548331.1979.11707630
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Chlamydia! Gecital Infections: A Growing Problem
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KIN
a
K. H OLMES and WALTER
E. STA MM
Uniuerstty of Washington
As a cause of urethritls, acute epldidymtUs. pelvic tnflammatory disease, and their complications, Chlamydia trachomatts ts rapidly outstrtpptng N. gonorrhoeae. Slgns and symptoms of chlamydiallnfecttons resemble those of gonorrhea, and rolnfectlon ts common, but treatment may be approprlate for gonococci but not chlamydiae. Guidelines are offered for diagnosls and effective treatment.
Although genital tract Infections wlth Chlamydia trachomatts have been recognlzed slnce the beglnnlng of this century, the organlsm was not consldered a major cause of sexually transmltted dlsease untll recently. Durlng the last decade. however. several studles have produced evidence that C. trachomatts causes both nongonococcal urethrltls ln men and pelvtc lnflammatory dlsease ln women. In fact. morbldlty from chlamydlal genital tract Infection ln this country now rivais and may exceed that from gonorrhea. Dependlng upon the population studled. more than half the cases of acute urethrltls are nongonococcal. and among certain groups. partlcularly male college students. 80% to 90% are nongonococcal. C. trachomatls causes 30% to 50% of these cases of nongonococcal urethrttls. ln addition. between one thlrd and two thlrds of men treated effectlvely wlth penlclllln or spectlnomycln for uncompllcated gonorrhea develop postgonococcal urethrltls. There ls strong evtdence that at !east half of these cases are due to slmultaneous acquisition of chlamydtal and gonococèal Infections. Our studles. as weil as thO!~e of J. D. Oriel ln England. have shown that men wlth laboratory-proved mlxed Nelsserta gonorrhoeae and C. trachomatls urethritls almost lnvarlably develop postgonococcal urethritls after penlcillin therapy for gonorrhea. From what ls known of the pecullar ltfe cycle of chlamydiae. descrlbed ln a prevtous article by E. R. Alexander (see "Chlamydia: The Organism and Neonatal Infection," HP. July 1979). lt ls probable that C. trachomatls has a longer Incubation perlod than N. gonorrhoeae and therefore does not cause symptoms of urethrltls untll two to three weeks after antlblotlc treatment for gonorrhea. Noteworthy ln this regard ts the fact that of the treatment regtmens for gonorrhea recommended by the Center for Disease Control. only one the
tetracycline regi men - ts effective agatnst chlamydlae. Treatment of gonorrhea wlth penlcllltn G. amplclllln. or specttnomycln will eradtcate N. gonorrhoeae but not C. trachomatls. The dtagnosts of nongonococcal urethrttls cannot be made solely on cllnlcal grounds. The slgns and symptoms are slmllar to those of gonorrhea. tncludtng meatal erythema and tenderness. urethral discharge, dysurla. or urethral ltchlng. ln general. however. nongonococcal urethrltts ls Jess severe than gonorrhea. and a substantlal proportion of men wtth proved C. trachomatls Infection of the urethra have no overt slgns and symptoms of urethritls. ln practtce, the dtagnosls of nongonococcal urethrltls ls usually made on the basts of an overt leukocytlc urethral exudate on physical examtnatlon and the absence of N. gonorrhoeae on a gram staln of the exudate. Subsequent cultures also should be negative for gonococcl. To make a presumptlve dlagnosis of nongonococcal urethritls ln the absence of overt urethral exudate. one should examine a specimen of urethral secretions obtalned wlth a small endourethral swab. A gram stain of the specimen ls flrst scanned at law power to ldenttfy areas of the sllde contalnlng maxImal concentrations of leukocytes. These areas are then examlned under oll Immersion. An average of four or more leukocytes per l.OOOX field ln at !east three of flve fields indicates urethritts and also correlaies wlth recovery of C. trachomatls. Alternatlvely. the
Dr. Holme11 111 Profellsor of Medldne. University of WtUblngton.
and Cblef, Division of lnfectlow DlletUn, U.S. Public Healtb Service Ho1pltal, Seattle. Dr. Stamm ls A11lstant Profnsor of Medldne, University of WtUblngton. and Codi!Yctor, Harborvlrw Medical Center Sexually Transmllled Dlsea~~e Cllnlc, Seattle. Hospital Practtce October 1979
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demonstration of pyurta, deflned as 15 or more leukocytes per 400X microscopie field. ln the sediment of flrst-votded early-morntng urine alsa provldes presumptive evidence of C. trachomatts Infection ln asymptomatlc or symptomatic men wtth a htstory of exposure to sex partners wlth nongonococcal salptngttis or mucopurulent cervlcltis, and ln fathers of chlldren wtth Inclusion conjunctivltis. Unfortunately, Gtemsa-statned or lmmunofluorescent smears of urethral exudate are tnsensttive ln the specifie dtagnosts of chlamydtal genital tract Infections. A specifie etiologie dtagnosts ts therefore not routinely sought ln patients wtth nongonococcal urethrttis. Dlfferentiation of the 40% to 50% of cases caused by C. trachomatts from the remalntng Idiopathie cases depends on Isolation of C. trachomatts ln tissue cell culture or on serologie evidence of Infection. Bath procedures are dlfflcult to perform and nelther ts readlly avallable. although most vlrology laboratortes can perform tissue culture Isolation of C. trachomatts. To obtaln an adequate specimen tt ls necessary to tnsert an endothelial swab 1 to 2 cm tnto the urethra. The specimen should be placed ln a transport medium contatnlng pentctllln and streptomyctn and sent to a vlrology laboratory for culture. A mtcrolmmunofluorescence test ustng C. trachomatts antigens. developed by S.-P. Wang and J. T. Grayston at the University of WashIngton, measures antibodles by lmmunotype spectflclty and by tmmunoglobln class ln bath serum and local secretions. Although tt bas been greatly slmpllfted, tt still ts avallable only ln research laboratortes; tt ts as dtfftcult to perform as Nongonococcal uretbritis can oflen be distissue culture and requtres demonttngulshed from gonococcal by appearance of uretbral gram stain. Normal smear (top) stration of lgM antlbody or a fourshows no polymorpbonuclear leukocytes, fold rtse ln anttbody titer ln patred many transitlonal epithelial cells, occa· sera to dtfferentiate current from sional mononuclear cells, and noncellular past Infection. Studles by Grayston debris. ln nongonococcal urelbrltts, smear and Wang of C. trachomatts ocular (center) shows polymorphonuclear leukoInfection ln the monkey madel cytes and mononuclear lnjlammatory cells, showed that lgM lmmunofluoresbut no gonococcl. Gonococcal uretbrllis cent an tl body was demonstrable afsmear (bottom) shows many polymorphoter prtmary Inoculation but not after nuclear leulwcytes, sorne with gram-negarepeat challenge wlth the same tmtive lntracellular diplococcl ( GNID). 106
Hospital Practlce October 1979
munotype. Our cllnlcal experience supports thetr flndtng that lgM antibody or seroconverston tndtcates recent Infection. However, patients wlth mlld Infections often do not seek treatment untillt ts tao late to demonstrate a rtse ln antlbody tlter ln patred sera, and tt may not be possible to demonstrate IgM antibody ln a pattent who prevtously bas been tnfected wtth the same lmmunotype. For these reasons. serologie tests may not dtfferenttate past from current Infection. The recognlzed complications of chlamydia! urethrltis ln men are epldldymttis and posstbly arthrttts (Retter's dtsease). Epldtdymttls may also result from gonorrhea and from collform or pseudomonas urtnary tract Infection, but ln recent years the majortty of cases have been categortzed as "idiopathie," stnce a causative organtsm often cannat be found. Idiopathie eptdldymttis bas been attrtbuted to chemtcal Inflammation caused by reflux of sterile urine down the vas deferens, but the condition ts most frequently dtagnosed ln young men wtth a hlstory of nongonococcal urethrttis. We have found evidence of C. trachomatls Infection ln association wtth most acute eptdtdymttis ln young men. In our study of 50 men wtth acute epldldymltis, C. trachomatls was demonstrated by Isolation of the organlsm or by a rtse ln mtcrotmmunofluorescent antibody tlter ln 17 of the 34 who were under 35 and ln none of the 16 men over 35 years of age. ln the younger group. the organlsm was found ln 16 of 24 who bad no other pathogen recovered and no his tory of sc rotai trauma and wh ose condition ln the past would have been termed Idiopathie epldtdymttis; ln flve of stx such patients ln whom eptdtdymal aspiration was done, C. trachomatts was lsolated dtrectly from the asptrates. Only seven men, ali under 35, bad gonorrhea. Coltform or pseudomonas organtsms were tsolated from 12 of the 16 men ln the older group but from only one of the 34 ln the younger group. These results tndtcate that acute epldldymltis ln men under age 35 ts usually caused by
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C. trachomatts or N. gonorrhoeae, whlle Infection wtth coltform bacterta ts the most frequent cause ln older men. Certain cltnlcat and epidemiologie features help to dtstlngulsh chlamydia! eptdldymttts from that due to coltform Infection. A htstory of recent sexual exposure was more common among those wtth chlamydlal or gonococcallnfectlon than among those wtth coltform Infection. On examlnatlon. urethral discharge could be expressed from 11 of 17 men wtth chlamydtal eptdtd-
ymltts. seven of seven wtth gonococcal urethrttts, but only three of 13 wtth coltform or pseudomonas Infection and three of 13 who had no deftnlte pathogen recovered. Thus. age. recent sexual exposure, and presence of urethrttls help to dlsttngulsh men wtth chlamydtal or gonococcal eptdldymttts from those wtth epldldymltls of other etiologies. Among men wtth acute epldldymltls who have demonstrable urethral exudate. a gram-stalned smear and culture may reveat N. gonorrhoeae. A presumptlve dlagnosts of chia-
mydtal eptdtdymltls ls warranted ln those who have urethral dlscharge but negative tests for gonorrhea. Although chlamydia! epldldymltls may not be assoclated wtth acute urethrltts, the major diagnoses to conslder ln young men wlth acute testtcular swelllng and/or pain are torsion. whlch should be ruled out by Doppler flow studles; radionuclide scan or surglcal exploration; direct trauma to the scrotal contents; and tumor or tuberculosls, whlch are suggested by fallure to lmprove wtth tetracycltne therapy. Hoepltal Practtœ October 1979
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A cu te epididymitis is often diagnosed as idiopathie, but culture of 11rlne or materlal from genital sites rer•ealed Infection in the majorlty of the 50 patients studied. C. trachomatis was iso/ated more frequent/y from men under 3'5 years of age, coliform organisms and Psmdomonas more often from those or•er 3 5. A mong tbose in yormger age group, er•ldence of C. trachomatis infection also u•as fou nd, by l$olation or serocom•erslon. ln one patient witb N. gonorrhoeae and one with idiopathie epididymitis, respectlr•ely.
The most serlous condition that often arises as a complication of nongonococcal urethrltls ls Relter's dlsease. It reportedly occurs ln fewer than 1% of patients wlth urethrttls, but lt can be serlous and chronlcally debilltatlng, lnvolving the eyes, Joints, skln, and mucous membranes. Symptoms usually appear one to four weeks after onset of urethrltls. Ocular symptoms range from mlld translent conJunctlvitls to severe uveltls, whlch frequently relapses and may result ln bllndness. The arthrltls ls usually asymmetrlc and affects the large Joints of the lower extremltles or the sacroillac Joints, Achilles tendons, and plantar fasclae (see R. Bluestone, "The Seronegative Spondylarthropathles, page 87 ). The Initial episode may be dlsabllng and often lasts for several months. Eventually the symptoms remit spontaneously, but recurrences are corn mon. The dermatologie manifestations of Relter's dlsease lnclude balanltls clrclnata; keratoderma blennorrhaglca lnvolving the soles of the feet and, ln sorne cases, the palms 108
Hospital Practlce October 1979
of the hands or other parts of the body: and small superflclal ulcers of the palate, tongue, and oral mucosa. Although the penlle and sktn lesions look qulte dramatlc, they are usually palnless. Among men wlth untreated acute Reiter's dlsease, Hausa et al demonstrated C. trachomatls urethral Infection ln two thlrds of those wlth urethrltls. We have lsolated C. trachomatls from a slmilar proportion of patients with acute urethrltls and Relter's dlsease, as weil as from thelr sex partners. Therefore, treatment wlth tetracycline Js advisable for both pattent and sex partner. Antiblotic therapy may cure the underlylng Infection, but there ls no known cure for Reiter's dlsease. There ts strong evidence that Relter's dlsease has a genette basls. Over a decade ago, G. W. Csonka noted a famlllal tendency, and R. Morris and assoclates subsequently found that 96% of thelr patients wlth Relter's dlsease possessed the HLA-B27 hlstocompatiblllty antigen. compared with only 8% of a control group. Other studles have shown a relationshlp
between Relter's dlsease, ankyIoslng spondylltls, and the HLA-B27 antlgen. Although 1t has not been proved, it appears possible that ln genetlcally susceptible lndlviduals, Infection wlth the causative agent of nongonococcal urethrttls lnltlates the manifestations of the dlsease. The drug of cholce ln treatlng nongonococcal urethrltls ls tetracycline hydrochlorlde. The treatment reg! men recommended by the Center for Dlsease Control ls 500 mg qtd for seven days. Alternative tetracycline reglmens that can be used lnclude doxycycline, 100 mg btd for seven days. However, we believe 100 mg once dally for seven days may be Just as effective. Nearly every pattent wlth nongonococcal urethrltls lmproves on this regimen, although many continue to have a clear mucold urethral discharge, whlch eventually resolves after treatment ls completed. Since no tetracycline-resistant stralns of C. trachomatts are known, failure to show lmprovement on tetracycline therapy suggests that the patient ls not complylng, that the dlagnosls should be reevaluated, or that Infection may be due to a mlcroorganlsm other than C. trachomatls. It ls known, for example, that about 10% of stralns of Ureaplasma urealyttcum, a genital mycoplasma that probably causes sorne cases of nongonococcal urethrltls, are htghly resistant to tetracycline hydrochlorlde. Erythromycln base ls effective agalnst C. trachomatls and moderately effective agalnst U. urealyttcum ln vitro, and lt cao be used ln the same dosage, 500 mg qld for 14 days, ln patients who do not lmprove on tetracycline. It ls also essential to offer treatment wlth tetracycline or erythromycln to the patlent's sex partner. When a patient falls to respond to elther of the treatments suggested above, other diagnoses to conslder lnclude urethrallnfectlon with herpes slmplex virus or Trichomonas vagtnalls, persistent Infection of the perturethral glands or prostate, or anatomie abnormalltJes of the urethra, such as a strtcture. In most cases of herpesvtrus Infection, charactertstic herpetlc penlle lesions are
can be dlagnosed by examlnlng the sediment of flrst-voided urine. The diagnosls of prostatltls can be establlshed uslng the flve-glass collection technique of Stamey and coworkers. Urethroscopy may be necessary to assess the posslblllty of urethra.l anatomie abnormall.tles. Although perststence of urethrltls wlthout improvement ls uncommon durlng tetracycline therapy of nongonococcal urethritls. recurrence of urethrltls wlthln two to six
weeks after therapy is common and presents the major therapeutlc dllemma. In our recent experience, 47% of men wlth chlamydia-negative nongonococcal urethrltls have perslstence of the condition or. more often, recurrence wlthln six weeks after tetracycline therapy. In contrast, only 17% of men wlth urethrltls due to C. trachomatts have recurrent nongonococcal urethrltls wlthln six weeks after tetracycline treatment. and this organlsm usu-
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present, but ln an occaslonal patient these lesions may be lnslgnlflcant or absent. In such cases. the presence of tender Inguinal adenopathy and/or an area of focal tenderness noted on urethral palpation suggest herpetlc urethrltls, provtdlng gonorrhea deflnltely has been ruled out. T. vagtnalts Infection, an uncommon cause of nongonococcal urethrltls, should be considered only when a patient falls to respond to tetracycline. It
Hospital Practlce October 1979
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Manifestations of Reilt.,.'s diseme lm·lude mymmetrlc sU'elllnl( atld Inflammation of tbt• jolrlls, as shou•n ln tbt• photol(rapb (top lefi) and tbt.,.,WJ(ram from patient u•llb foot fulltl und llt'J(atit't' .'1:-ravs ( hollom ). and skln /t>sllms, su ch as kt.,.atodt.,.ma hlennorrbal(kum of the solt•s of lbt• ft•t•t (top rll(bt ). C. rrachomaris bas heen l.wlalt•d from tu•o tblrds of lht• patit•nt.r u1tb Rt•llt.,.'s dlsra.w, oaurrlnl( as a sequt'la of nonl(onococctll un•thrltls. ( 7bt.,.,WJ(ram and photo, top rll(bl, murtesv of Dr. Rotlm')•IJiurstone.)
l l0
Hospital Practtce October 1979
ally cannot be retsolated from such patients. Wtth more prolonged foiJow-up, however, chlamydia-positive recurrences are occastonally seen. Stnce latency ts an Important aspect of chlamydia! Infection, tt ts dtfftcult to know whether these late recurrences represent relapse or retnfectton wlth C. trachomatts. The organtsm has a two-phase llfe cycle, exlsttng as an extracellular nonrepllcattng form capable of lnfectlng host cells and as a nonlnfectlous obllgate lntracellular replicattng form. lt may survive as an lntracellular parasite even whlle lts multiplication ls held ln check by host defense mechanlsms. Bath c. pstttact and C. trachomatts stralns are known to cause relapslng discase many years after the original Infection. For Instance, treatment wlth cortisone eye olntment can reacttvate acute trachoma ln a pattent wlth long-dormant eye infection. On the other hand, as wlth any sexually transmttted dlsease, the late-recurrence rate of chlamydia) genital Infections may be attrtbutable to relnfection. Optimal therapy for carly recurrence of nongonococcal urethritl" after Initial lmprovement on tetracycline has not yet been weil deflned. One can glve a prolonged course of treatment wlth tetracycline (e.g., 500 mg btd for 30 days) and make certain the sex partner recetves stmultaneous treatment. Men who have had carly recurrence after treatment may be encouraged to use a condom durtng Intercourse for at !east two months, whlch will help dtffcrentlate relapse from relnfecUon ln any subsequent recurrence. Alternative treatment reglmens for patients wlth carly recurrence lnelude erythromycln, 500 mg qid for 14 days, or sulflsoxazole, 500 mg q 1d for 10 days. Penlcllll n and amplclllln are much Jess effective than tetracycline or erythromycln agalnst chlamydial Infection and are of little or no value ln nongonococcal urethrltls. Most regimens recommcnded for the treatment of syphilis and gonorrhea, cxcept the tetracycline reglmen, are not effective agalnst chlamydlal genl(contlnued on page 115)
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CHLAMYOIAL
(from page 110)
tai tract Infections, and C. trachomatts ts not reltably eradtcated by stngle-dose therapy wtth any antlmtcroblal. The optimal treatment for chlamydlal eptdldymttis ts tetracycline. 500 mg q t d for 10 days. Genital C. trachomatts Infections, like genital N. gonorrhoeae Infections, produce even more morbldlty ln women than ln men. C. trachomatts has been lsolated from the cervtx of 20% to 60% of women wlth gonorrhea or a hlstory of contact wlth gonorrhea. ln women wtthout gonorrhea, chlamydtae have been tsolated from the cervtx ln 10% to 20% of females seen ln
VD cltntcs and ln about 5% of those attendlng gynecology or prenatal clinlcs. ln prenatal clinlcs servtng Indigent populations. up to 25% of pregnant women have bad C. trachomatts Infection of the cervtx. These flndlngs lndlcate that mlxed gonorrheal and chlamydlal Infections frequently are present ln women as well as ln men, partlcularly ln the young. sexually active patient population seen ln VD clinlcs. The symptoms and stgns of C. trachomatts genital tract Infections ln women resemble those of gonorrhea and, as wtth gonorrhea ln women. may be mtld enough to be tgnored or may be entlrely absent.
Both gonorrhea and chlamydlal Infection may cause a mucopurulent cervical exudate, usually assoclated wlth erythema. edema. congestion. and lncreased frtabtltty of the cervtx. Cervtcltis due to herpes slmplex virus Infection can be confused wtth gonorrhea or chlamydlal cervtcttts. but lt usually causes Inflammation and ulceration of both the exocervtx and endocervtx rather than the endocervtx alone. ln Seattle. N. gonorrhoeae has been recovered from the cervtx ln 50% of women wtth pelvtc tnflammatory dlsease. C. trachomatts bas been tsolated from the cervtx ln 20%. whtle another 10% of patients show an antibody response to tt.
Tr~atm~nt results i_n the National Gonorrhea Therapy Monitoring Study probably represent minimum estimates of efficacy since remfect1ons were mcluded as treatment failures. Data from N EngiJ Med 294:1, 1976
Hospital Practtce October 1979
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Thus, C. trachomatis may be lnvolved ln about 30% of the pelvtc lnflammatory dlsease seen ln Seattle. Mlxed infections wtth N. gonorrhoeae and C. trachomatts are commonly found in pelvtc inflammatory dlsease, making tt difflcult ln sorne cases to know which organlsm ls responslble for the Infection. Recent reports from Sweden suggest that C. trachomatts has become the main cause of pelvtc lnflammatory dlsease there (N. gonorrhoeae ls lsolated ln only 10% to 20% of cases. whereas at least 30% may be due to C. trachomatts). ln one study. C. trachomatts was isolated from the cervlx ln 19 of 53 women wlth acute salplngltls vertfied by laparoscopy and was recovered from the falloplan tubes, ln the absence of other pathogens, ln six of seven patients who had C. trachomatts ln the cervtx. ln addition, hlgh tlters of serum antlbody to C. trachomatts, often wtth three- or fourfold changes ln ttter, have been demonstrated ln an even hlgher percentage of pelvtc lnflammatory disease cases ln another Swedlsh study. lgM antlbody to C. trachomatts has also been demonstrated ln the majortty of women wtth acute perltonttls and/or perlhepatltis (Fitz-Hugh-Curtis syndrome) ln two recent studles. As noted prevtously, the presence of IgM anttbody lndicates recent C. trachomatts Infection. These data suggest C. trachomatts may cause sorne cases of acute perlhepatitts, whlch formerly had been attrlbuted excluslvely to N. gonorrhoeae. C. trachomatts has also been tsolated from Bartholln's duct ln patients wlth barthollnttls and from the rectum of women wlth C. trachomatts cervical Infection. Recent data suggest C. trachomatis can be recovered from the female urethra almost as often as from the cervtx and may be a cause of the urethral syndrome (dysurla and freq uency wtthout slgnlflcant bacterturla). Besldes caustng morbldlty ln adult women, C. trachomatts genital tract Infections carry the rtsk of perinatal transmission of Infection to the neonate. Inclusion conjunc116
Hospital Practlce October 1979
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Uvttts and an afebrtle pneumonla ln Infants, revlewed by Alexander, are now recognlzed consequences of maternai chlamydlal genital tract Infections. Maternai C. trachomatls Infection durlng pregnancy also bas been recently lmpllcated as a possible cause of fetal wastage and neonatal death and bas been assoclated wlth a hlgh rlsk of postpartum endometrltls and salplngltls. U ls not clear at present whether these perinatal and postpartum complications are dlrectly attrlbutable to C. trachomatls, and tt ls premature to recommend rouUne screenlng ln ali pregnant women. Conflrmatory studles are requlred. However, tt ls especlally Important to detect and treal chlamydia) genital Infections ln women ln certain other situations. Definitive dlagnosls of cervlcltls due to C. trachomatts depends on Isolation of the organlsm from an endocervlcal swab lnoculated lnto tissue culture ln a vlrology laboratory. ln practice, however, the presence of mucopurulent endocervlcltis suggests elther chlamydlal or gonococcal Infection. If tests for gonorrhea are negative, the patient "'h'luld be treated wlth letracycllne or erythromycln for presumed chlamydlallnfectlon, and male sex partners should be examlned for nongonococcal urethrltls. Simllarly, ali women who are recent sex partners of men wtth nongonococcal urethrttts (I.e., wlthln six weeks before onset of symptoms ln the male) should recelve approprlate therapy. The treatment for cervical chlamydlal Infection ls tetracycllne hydrochlorlde, 500 mg qld for seven days. For pregnant patients, erythromycln base, 500 mg btd for 14 days, should be used. Both regimens eradlcate C. trachomatts from the cervlx. For salplngltls, prellmlnary evidence lndlcates that tetracycline hydrochlorlde, 500 mg qtd for 10 days. produces cllnlcal and microbiologie cure. Studles currently are ln progress to determine what proportion of young women wtth the urethral syndrome have chlamydlallnfectlon, and whether such patients beneflt from antlmlcroblal therapy.
lntracellular chlamydia/ Inclusion bodies ( anou•) apparent ln cervical blopsy specimen are diagnostic of cblamydlal cervldtls but are rare/y seen ln endocenlfcal swab samples. Deflnltlr'e dlagnosls usually requlres Isolation ln tissue culture.
Slnce C. trachomatts Infections are more than twlce as common as gonorrhea. the morbldlty from chlamydlal genital tract dlsease ls rapldly outstrlpplng that of gonorrhea. The lncreased Incidence of genital chlamydia) Infections undoubtedly ls related ln part to changes ln sexual behavlor but has also resulted from the fact that little or no effort ls belng made to trace and treat sex partners of lndlvlduals wlth proved Infection or to detect asymptomatic lndlvtduals. ln contrast, these measures have been relatlvely effective ln the control of gonorrhea, partlcularly ln populations that have made good use of such control measures. Chlamydlal genital tract Infections have been
weil documented ln the sex partners of patients wlth nongonococcal urethrltls or endocervlcltls. The current situation wlth asymptomatlc chlamydlal genital tract Infections ls analogous to the probJem of asymptomatlc gonococcallnfectlon ln the sex partners of patients wtth gonorrhea. Chlamydlal genital tract Infections pose an addltlonal problem, however, both because they are more common and because facllltles for the specifie dlagnosls of C. trachomatls are not readlly avallable. 1t seems advlsable, therefore, to treat patients wtth cllnlcal slgns and symptoms of chlamydlal Infection wtth an effective antlblotlc regi men and to offer slmllar treatment to thelr partners. o
Selected Reading Holmes KK et al: Etlology of nongonococcal urethrttls. N Engl J Med 292:1199, 1975 Bowte WR et al: Etlology of nongonococcal urethrttla: EVidence for ChlamJ1dla tmchomatfs and Ureaplaama ureal11ttcum. J Clin ln\'est 59:735, 1977 Schachter J: Chlamydlallnfectlona. N Engt J Med 298:428. 490, 1978 Holmes KK. Hobson D (Edal: Nongonococcal Urethrttls and Related Infections. Amertcan Society for Mlcroblology, Waahlngton, DC. 1977 Berger RE et al: Etlology, manlfeatattons. and therapy of acute epldldymltls: Prospectt\'e atudy of 50 eues. J Urol 121:750, 1979 Kousa M. Salkku P. Richmond S, Lassus A: Frequent association of chlamydia Infection wtth Reiter'• syndrome. Sex Transm Dia 5:57, 1978
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