British Journal of Venereal Diseases, 1980, 56, 37-45

Chlamydial infection of the cervix in contacts ofmen with nongonococcal urethritisI ANNE TAIT,* ELISABETH REES,* D HOBSON,t RUTH E BYNG,tAND M C K TWEEDIE*From the Departments of * Venereology, tMedical Microbiology, and *Biostatistics, University ofLiverpool, Royal Liverpool Hospital, Liverpool

SUMMARY An investigation of chlamydial infection in sexual contacts of patients withnongonococcal urethritis (NGU) was carried out to determine the clinical signs of infection in thecervix, and their response to chemotherapy, and the incidence of cervical infection in the presenceof ectopy and oral contraception.

In 202 consecutive female contacts of NGU the isolation rate of Chlamydia trachomatis was35%. Hypertrophic ectopy and endocervical mucopus were present in 1907o and 37% ofchlamydia-positive patients respectively and, in all but one, resolved after treatment. Only 14% ofthose followed up after treatment developed yeast infections. The chlamydial isolation rate wassignificantly higher in patients with hypertrophic ectopy and endocervical mucopus. Cervicalectopy and oral contraceptives acted additively, each producing a significant effect on thechlamydial isolation rate in the presence of the other but not when present alone.

Introduction

The clinical diagnosis of nongonococcal urethritis(NGU) in men is often arbitrary and commonlybased solely on the finding of 10 polymorphonuclearleucocytes per high power field (x 100 objective) in aurethral smear with no evidence of Neisseria gonor-rhoeae. However, strong evidence, recently reviewedby Schachter,' has now accumulated for a causativerole for Chlamydia trachomatis in up to 50% of menwith NGU and for the sexual transference of thisagent.

In women, the commonest site of chlamydial infec-tion (as in gonorrhoea) is the cervix,2 3 the site ofgreatest coital contact, but C trachomatis may alsobe isolated-although less frequently-from therectum,4 the urethra,5 and Bartholin's ducts.6

Criteria similar to those used in the diagnosis ofNGU in men cannot be applied to cervicitis becausethe endocervical secretion contains polymorpho-nuclear leucocytes which vary in number accordingto hormonal factors and coital history. Until theclinical signs of infection and related symptoms wereinvestigated in conjunction with rapid tissue culture

Address for reprints: Dr I A Tait, Department of Venereology,Royal Liverpool Hospital, Prescot Street, Liverpool L7 8XP

Received for publication 25 June 1979

procedures for chlamydial isolation (based onmethods of Gordon and Quan7) the diagnosis ofnongonococcal cervicitis in women was unsatisfac-tory owing to the absence of a known aetiologicalagent.The difficulties associated with interpreting clinical

signs in the cervix have previously been discussed indetail.8 The same method of categorising the state ofthe ectocervix is used here; it is based upon the con-cept that ectopy (erosion) is not a pathological condi-tion but simply ectopic columnar epithelium whichextends from the endocervix to the ectocervix.9 1 Theredness which is associated with such ectopy-andsometimes thought to represent inflamma-tion-results from the sub-mucosal capillary bedbeing viewed through a single layer of columnarepithelium instead of many layers of squamousepithelium. Irregularity of outline with peninsulaeand islands of squamous epithelium together withNabothian follicles (ducts of mucus glands blockedby metaplastic squamous epithelium) indicatesmetaplasia which is, in most cases, physiological butmay be dysplastic.1" When an area of ectopy isoedematous and congested and bleeds, we havecalled it "hypertrophic". This appearance was firstdescribed as "cobblestone" by Dunlop,'2 who alsoreported the presence of "follicles" on colposcopicalexamination of the cervix. Together with mucoid or

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mucopurulent endocervical discharge these twosigns, singly or combined, indicate endocervicitis.At present there is no consistent management of

sexual contacts of men with NGU. Some physiciansrefer all contacts for investigation and give treatmentto all on epidemiological grounds, irrespective ofclinical or microbiological findings. Others are selec-tive in both their referrals and their treatment. Manyphysicians have been deterred from givingepidemiological treatment-in the absence of symp-toms-as candidosis might ensue. However, womenwith gonorrhoea are commonly asymptomatic andwithout clinical signs. They are treated when Ngonorrhoeae is isolated because it has been establish-ed that failure to treat may lead to serious conse-quences for the patient herself and for the com-munity. It is therefore important that the pathogenicrole of C trachomatis in women should be defined;(a) to establish the need for the treatment of knowninfections; and (b) to provide information forphysicians who may have to manage their patientswithout isolation facilities.

This paper gives the results of an investigation ofchlamydial infection in 202 women who were sexualcontacts of men with NGU with particular regard to:(a) the incidence of clinical signs and their responseto treatment in patients from whom C trachomatiswas isolated; (b) the presence of concurrent infec-tion; and (c) the incidence of chlamydial infection inpatients with cervical ectopy and in those taking con-traceptive steroids and the possible interrelationshipof these two factors on the isolation rate of thisagent.

Patients and methods

CLINICAL INVESTIGATIONSThe group of women examined consisted of 202 con-tacts of men with NGU who attended LiverpoolRoyal Infirmary consecutively on specified days. Allthe male contacts had been diagnosed in sexuallytransmitted diseases (STD) clinics where facilities forisolation of C trachomatis were not available.Women who had received antibiotics in the fourpreceding weeks were excluded. Known cases or con-tacts of gonorrhoea were also excluded as that infec-tion can also cause endocervicitis.

ln this group of women, 169 presented withcontact slips; the remainder attended of their ownaccord, or were referred by another doctor, and gavea history that their sexual contact was attending amale STD clinic. In these cases, the diagnosis wasalways obtained from the clinic named.Swabs for detection of N gonorrhoeae were taken

from the urethra and endocervix on at least twoseparate occasions and used to inoculate a selective

medium containing antibiotics (London Analyticaland Bacteriological Media Ltd, London) and make asmear for Gram staining. All patients were investi-gated for syphilis by conventional methods and fortrichomoniasis and yeast infection by inoculation ofFeinberg-Whittington medium. (Yeast infection wasonly recorded if cultures gave positive results evenwhen clinical signs and symptoms suggesting the con-dition were present.) Swabs for culture for Ctrachomatis were taken from the endocervical canaland, in addition, rubbed on any ectopic columnarepithelium as previously described.6 Swabs were nottaken from the urethra.

LABORATORY TESTSSwabs for culture for C trachomatis were immedi-ately placed in 2-3 ml of transport medium'3 andstored directly at 4°C until inoculated into tissueculture. This was usually done two to four hoursafter the swab had been taken but occasionally afterstorage for 24 hours.Swab contents were thoroughly dispersed into

transport medium and 0 4 ml were inoculated on toeach of two 16-mm coverslip cultures of replicatingMcCoy cells (that is, cells not pre-treated byx-irradiation or any anti-replicative chemical agents).Centrifugation-assisted absorption of the inoculumon to the McCoy cells as well as incubation condi-tions and method of examination of inoculatedcultures after 48-72 hours' incubation have all beendescribed previously.'4

In all cases, the total number of intracellular inclu-sions of C trachomatis recovered from each clinicalspecimen on the McCoy coverslip culture wascounted. The inclusions detected represent a singlecycle of development; their number therefore reflectsthe number of infective particles in the originalcervical swab and is a direct measure of the numberof particles being shed from the lesion. The purposeof this quantitative procedure was (a) to check thesensitivity and reproducibility of the laboratorymethod and (b) to have additional data against whichthe severity, response to treatment, and possibility ofrelapse might be assessed.

In all cases, the results represent the primaryinoculation of specimens in tissue culture. No secondpassage from tissue culture to further tissue culturewas performed to avoid any risk of false-positiveresults by cross-contamination.

CLINICAL SIGNSThe clinical signs were recorded on the request formand case sheet at the time of sampling.The state of the ectocervix has been recorded in

three categories: no ectopy, simple ectopy, andhypertrophic ectopy (Figs 1-3). The contents of the

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FIG I Cervix showing no ectopy.

FIG 2 Cervix showing simple ectopy.

endocervix have been recorded in three categories;clear mucus, cloudy mucus, and mucoid or muco-purulent discharge (Figs 4 and 5). In examining thecervical contents, care was taken to remove dischargeextruding from the cervix before the contents of thecanal were assessed and sampled. Cervical secretionspreading from the os into the vagina becomescontaminated by vaginal flora, thus appearingmucopurulent in some cases, whereas behind thisclear mucus may be seen in the canal.

FIG 3 Cervix showing hypertrophic ectopy withendocervical mucopus. (C trachomatis isolated.)

FIG 4 Cervix showing clear mucus with simple ectopy.

TREATMENTRoutine treatment of chlamydia-positive women waswith oxytetracycline hydrochloride tablets 250 mgsix-hourly for 21 days. Pregnant women were notgiven oxytetracycline but received erythromycin BP250 mg six-hourly. Treatment was given for 21 daysas this is the longest course advised for men withNGU and we did not want possible inadequate treat-ment to be a cause of persisting clinical signs orchlamydial reisolation or both.

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FIG 5 Cervix showing endocervical mucopus with simple

ectopy.

Patient compliance can be a problem with such

prolonged treatment. To assess this, blood sampleswere taken for serum tetracycline estimation at 14 or

21 days in 26 women. Patients were not told in

advance that the test was to be carried out; hence the

time of venepuncture varied from two to five hours

after the last dose. The range of tetracycline concen-

trations was 0 -53-2 -01g.tg per ml (mean= Il-2l1). This

suggests that patient compliance was good and that

the serum concentration was satisfactory (minimum

inhibitory concentration of oxytetracycline for C

trachomatis = 0 - 2pg/ml'15).

FOLLOW-UP

All chlamydia-positive patients were asked to attend

for review to check whether or not candidosis had

developed and to assess the response to treatment on

day 14 (of the course of treatment), on day 28 (that

is, seven days after completion of treatment), twice

more at three-weekly intervals, and subsequently at

six weeks, a total of three months' post-treatment

observation. Several patients agreed to co-operate by

continuing to attend at three-monthly intervals and

others returned with fresh symptoms or requesting

reinvestigation within that time.

Specimens were taken for culture for C tracho-

matis, N gonorrhoeae, Trichomonas vaginalis, and

Candida species on each post-treatment visit.

STATISTICAL METHODS

Statistical comparisons were made using the X2 test

with Yates's correction.

ResultsC trachomatis was isolated from 70 (35%) of the 202women.

AGEThe age range for all 202 women was 16-46 years(mean 25 years); in the chlamydia-positive group itwas 16-37 years (mean 23 years).

MARITAL STATEOne hundred and ten women were single (chlamydia-positive 36%) and 68 were married (chlamydia-positive 28/o), 23 were divorced or separated(chlamydia-positive 39%), and the status of one wasunrecorded.

HORMONAL FACTORSPregnancyFive patients were pregnant; two (onepositive) were in the first trimester,chlamydia-negative) in the second,(chlamydia-negative) in the third.

chlamydia-two (bothand one

Menstrual cycleNo significant difference was found in thechlamydial isolation rates in successive weeks of themenstrual cycle.

In those 184 women with a regular cycle of 28 days(± 2), the month was divided into four weeks, week 1starting from the first day of menstruation. The weekin which the swab for C trachomatis was taken wasrecorded in each case. The isolation rates are shownin Table I. In 18 (21% chlamydia-positive) the cyclewas irregular.

TABLE I Isolation ofC trachomatis in relation to the weekof the menstrual cycle

Menstrual cycle (week)

Isolation 1 2 3 4 Total

No of patients 45 66 42 31 184Chlamydia-positive (%) 17(38) 23(35) 15(36) 9(29) 64(35)

Oral contraceptionAt the time of examination, 99 women (48- 7%chlamydia-positive) were taking oral contraceptives.The methods of contraception for all 202 patientsand the distribution of these methods in relation tochlamydial isolation is shown in Table II.The chlamydial isolation rate was significantly

higher in women taking oral contraceptives than in(a) those not using oral contraception (X = 10-44,P=0-0012); (b) those using barrier methods(X2=8-51, P=0-0035); and (c) those using othermethods, excluding barrier methods (X2 =5-91,P= 0015).

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TABLE 11 Isolation of C trachomatis in relation to methodof contraception

Chlamydia-positiveMethod of No ofcontraception patients No %

None 52 15 29Oral contraception 99 46 49Stopped oral contraception

in past month 7 3 43Barrier 18 1 5-6Tubal ligation and IUCD 25 5 20Not known ITotal 202 70 35

IUCD = intrauterine contraceptive device

Despite the difference in percentage isolationbetween those using barrier methods and those usingno contraception, the difference in proportions is notsignificant at 5/o (X 2 -90, P = 0-089) but the lackof significance may be due only to the small numbersin the group using barrier methods.

SYMPTOMSThe incidence of symptoms and their distribution inrelation to chlamydial isolation is shown in Table III.No significant difference was found in the isolationrates in relation to any particular symptom.

TABLE 111 Distribution of symptoms, appearance of theectocervix, contents of the endocervix, and incidence ofconcurrent infections in relation to isolation of Ctrachomatis

NoNo of chlamydia- % ofpatients positive positive

Symptoms*None 103 34 49Discharge 61 22 31Irritation and soreness 31 17 24Urinary 24 11 16Abdominal pain 17 5 7Postcoital bleeding 3 1 1-4Dyspareunia 3 2 3

Appearance of ectocervixNo ectopy 95 21 30Simple ectopy 87 36 51Hypertrophic ectopy 17 13 19Not known 3 0 0Total 202 70 100

Endocervical contentsClear 101 27 39Cloudy 56 14 20Mucopus and mucoid 35 26 37Blood 10 3 4Total 202 70 100

Concurrent infectionsNone 110 40 57Candida spp 61 16 23Trichomonas vaginalis 15 10 14Warts (cervical and vulval) 10 4 6Other 0 0 0Total 70 100

*Patients may have had more than one symptom

CLINICAL SIGNSEctocervixThe appearance of the ectocervix in relation to thechlamydial isolation rate is shown in Table III. Theisolation rate was significantly higher in those with(a) ectopy (simple and hypertrophic), 47%o(XI=l125, P=0'0004); (b) simple ectopy, 41%(X = 6-97, P= 0-0083); and (c) hypertrophic ectopy,76%o (X2 = 17 * 67, P= 0 000026) than in those with noectopy, 22%.

Endocervical contentsThe distribution of contents in relation to thechlamydial isolation rate is shown in Table III. Theisolation rate was significantly higher in those withmucopus (74%) than in those with clear and cloudymucus (26%) (X2 = 27 14, P= 0 0000045).

SalpingitisSeventeen patients complained of abdominal pain ordiscomfort (five were chlamydia-positive). Only fourof these had clinical signs of salpingitis (two werechlamydia-positive.)

EFFECTS OF ORAL CONTRACEPTION/CERVICALECTOPY ON CHLAMYDIAL ISOLATIONTo assess the possible interrelationship between oralcontraception and cervical ectopy, both of whichindividually were found to be highly significant in theisolation of C trachomatis, the four possiblecategories were compared and analysed statistically(for this purpose simple and hypertrophic ectopywere combined) (Table IV):

(1) The isolation rates in patients with (57- 1%)and without (30' 2%) oral contraception in thepresence of cervical ectopy (X2 =6'06, P=0-014);(2) The isolation rates in patients with (57 1o%)and without (27' 3%) ectopy in those taking oralcontraception (X2 = 6' 3, P = 0'012);(3) The isolation rates in women with (27- 3%) andwithout (16'4%) oral contraception in the absenceof ectopy (X2 =0 97, P= 0- 32);(4) The isolation rates in patients with (30'20o)and without (16'4%) ectopy in the absence of oralcontraception (X2 = 2- 06, P = 0 15).Thus neither oral contraception in the absence of

ectopy, nor ectopy in the absence of oral contracep-tion, is associated with a significant increase in theisolation rate. On the other hand, a significantincrease is associated both with oral contraceptionwhen ectopy is present and with ectopy when oralcontraception is being used. Oral contraception andectopy may be said to act additively, neither beingassociated with a significant increase in the isolationrate when acting alone but jointly being associated

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with a significant increase when acting simul-taneously.The isolation rates in the above categories (Table

IV) differ to a very highly significant extent(X2 =22'95, P=0-000041).

TABLE IV C trachomatis isolation in relation to ectopy andoral contraception

Chiamydia-positiveNo of

Comparison patienits No %

Ectopy 99 45 45.5With OC 56 32 57-1Without OC 43 13 30- 2

No ectopy 94 19 20-2With OC 33 9 27-3Without OC 61 10 16-4

TotalWith OC 89 41 46-1Without OC 104 23 22-1

OC = oral contraception

CONCURRENT INFECTIONSThe presence of concurrent infection in relation tochlamydial isolation is shown in Table III. Onlynormal flora was found in only 110 patients (35%chlamydia-positive). A significant increase in theisolation rate was found only in the presence ofT vaginalis (x =5 89, P = 0 15). N gonorrhoeae waspresent in seven patients, of whom three werechlamydia-positive at the time of their first visit.

WHOLE-COVERSLIP COUNT (WCC)The range for the 70 chlamydia-positive patients was1-100 000 inclusions per whole coverslip. Thepossibility that the degree of infection (as representedby the WCC) may vary according to conditions suchas the presence or absence of oral contraception andclinical signs in the cervix was considered. The meancounts of the WCC in these conditions are given inTable V.

TABLE V Mean whole-coverslip counts in certain con-ditions

Condition Mean count

Oral contraceptionPresent 6185Absent 2071

Hypertrophic ectopyPresent 4895Absent 4906

Endocervical mucopusPresent 10 727Absent 1745

FOLLOW UPThirty-eight women were followed up for 2-14months. C trachomatis was reisolated from fivepatients (Table VI) and there was a strong possibilityof reinfection in four of the five cases.*

TABLE VI Post-treatmentfollow up

No of Chlamydialpatients reisolation

Duration of treatment(months)<2 8 2*2-3 4 14-6 15 17-8 79-10 111-12 1 1>12 2 1

No of visits1 4 1*2 11 3*3 64 8 15 46 3 17 18 1

*Two reisolates from one patient

Clinical signsEctocervix. Of 12 patients with hypertrophic ectopy,11 reverted to simple ectopy and metaplasia was com-plete in one.

Contents of the os. Of those patients followed upafter treatment, of 20 endocervices previously con-taining mucopus, eight became clear, 11 becamecloudy, and one contained mucoid material.

Yeast infectionOf 70 chlamydia-positive patients, 16 had positivecultures for Candida species when the chlamydialinfection was diagnosed; twenty-five patients whohad negative results for yeasts initially did not attendfor follow-up investigations. Of the remaining 29chlamydia-positive women with negative results foryeasts, who were treated either with tetracyclinehydrochloride or erythromycin (two), four (140%) (alltaking tetracycline) developed yeast infection.

Discussion

C trachomatis was isolated from 35% of the 202female sexual contacts of unselected men with NGU.Isolation rates of 22-42%3 1618 have previously beenreported in different parts of the world. Differences,

*Details of personal case histories may be obtained fromDr I A Tait.

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however, occur in the reporting of clinical signs in thecervix associated with chlamydial infection. Signs ofcervicitis have been recorded in 62-89%'17 19 20 butwere also present in 58%7o of uninfected women whowere contacts of NGU'7 and in 560/o of controlwomen attending a family planning clinic.20However, cervical ectopy (erosion, cervical discon-tinuity) was included as an abnormal clinical sign inall these reports and may account for thesedifferences.The site of the squamocolumnar junction is laid

down at the time of organogenesis and ectopy isfound in infants, children, and virgins.9 At certaintimes, particularly at puberty and first pregnancy,the ectopic columnar epithelium is replaced bysquamous epithelium (squamous metaplasia, Fig 6)with the result that ectopy is less common in the olderwoman.9 In a study planned to determine theprevalence and significance of cervical ectopy inwomen attending family planning clinics inEdinburgh, ectopy was found in 37% of 1400 womenand was significantly associated with younger agegroups, greater parity, and oral contraception.2'There was no significant association with thepresence of aerobic or anaerobic bacteria, Tvaginalis, or yeasts.

FIG 6 Cervix showing metaplasia and simple ectopy withclear mucus.

If signs of cervicitis are narrowly defined on

macroscopic examination as endocervical pus withinthe canal and oedema of the areas covered bycolumnar epithelium (hypertrophic ectopy or

cobblestone appearance as described by Dunlop)'2there is a highly significant association betweencervicitis and the isolation of C trachomatis. In thisseries of consecutive cases, mucopus was found in370o of chlamydia-positive cases compared with 7%of chlamydia-negative cases (P=0 0000045), andoedema (hypertrophic ectopy) in 19% of chlamydia-positive compared with only 301o of chlamydia-negative cases (P=0 000026). The incidence ofendocervical mucopus is similar to that found inwomen with chlamydia-negative gonorrhoeaexamined in this unit. In each infection, macrosopicevidence of the endocervical infection is absent in50-60%'o. After treatment of the chlamydial infection,clinical signs of oedema and mucopus disappeared inall but one patient.Symptoms associated with endocervicitis are

difficult to interpret because the area of susceptiblecolumnar epithelium, and therefore the consequentamount of mucopus which may be produced, isrelatively small. Excessive mucus production by thecervical columnar epithelium due to the pro-gestational effect of contraceptive steroids, or due toa large area of ectopy, may result in a dischargewhich is not associated with infection of any kind. Inaddition, even a mild vaginitis due to commonvaginal pathogens such as T vaginalis or yeasts mayresult in a noticeable discharge owing to the largearea of squamous epithelium of the vagina affected.

Consequently, symptoms may bear little relation-ship to cervical pathology in a large number ofwomen. In this series, no significant relationship wasfound between the presence of chlamydial infectionin the cervix and any of the symptoms. Similarfindings have been reported by others.20 22 23 IndeedBurns et al'6 reported a significant absence ofsymptoms in the presence of chlamydial infection.However, Paavonen et al'9 found chlamydia-positivegynaecological patients had significantly more ocularand urethral symptoms than chlamydia-negativepatients.

Thus, C trachomatis infection appears to beassociated with certain well-defined signs of cervicitisin some patients and probably these signs are causedby that infection. On the other hand, with ectopythere is also a definite relation to chlamydial infec-tion but, for reasons already discussed, simple ectopycannot be considered to be part of the sign-complexof cervicitis. It seems possible that ectopy may be oneof many possible interrelated factors which allowinfection to be more easily acquired. For example,the virulence of particular serotypes of chlamydia,the immune status of the patient, and anatomical andhistological variations may all influence the ease withwhich infection of the tissues is established.Harkness24 found a higher prevalence of hypospadias

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(a condition in which columnar epithelium extends tothe external urethral surface since the fossanavicularis is absent) in patients with NGU andgonorrhoea than in the normal population. Cervicalectopy may have a similar effect in chlamydial infec-tion and may be more important than in gonorrhoeabecause of the intracellular developmental cycle ofchlamydia.Our findings indicate that only in patients in whom

the two factors, contraceptive steroids and ectopy,are present is there a significant increase in theisolation rate of C trachomatis (P = 0O 00004). Neitherfactor in the absence of the other is significant. Apartfrom an implied absence of any barrier to infectionof the cervix, oral contraceptive steroids mayfacilitate cervical infection by their progestationaleffect, which is similar to that produced in the firsttrimester of pregnancy. They produce an excessiveoutflow of alkaline mucus from the endocervicalglands and increase the bulk of the cervix, producingeversion with further ectopy. It is noteworthy thatsteroids added to McCoy tissues cultures infectedwith C trachomatis increase the size and number ofinclusions developing.25The interdependence of several varying factors

may explain some of the disparity about the effect oforal contraceptives on the chlamydial isolation ratepreviously reported. 16 17 20 23

Like Oriel et al,23 but unlike Hilton et al,20 wefound no variation in the isolation rate according tothe week of the menstrual cycle.The increased chlamydial isolation rate in the

presence of T vaginalis may reflect the frequencywith which multiple sexually transmissible agents areisolated in promiscuous patients.26 Others havefound no relation between the chlamydial isolationrate and any other concurrent nongonococcal infec-tion.23The mean whole-coverslip counts were raised in

patients taking oral contraceptive steroids and in thepresence of endocervical mucopus but not in thepresence of hypertrophic ectopy. It is possible thatoral contraceptive steroids facilitate chlamydialcervical infection, and the presence or absence ofendocervical mucopus indicates the severity of theinfection, whereas hypertrophic ectopy merelyindicates a general host-response to infection in somepatients. The possible influence of these clinicalfactors on the degree of chlamydial replication ininfected women will be discussed separately.

In addition to causing acute cervicitis Ctrachomatis has been isolated from the fallopiantubes in cases of pelvic inflammatory disease con-firmed at laparoscopy and associated with a four-fold rise in chlamydial antibody titre.27 Clearly, it ispotentially a serious pathogen in women.

This work was supported by a project grant from theMedical Research Council. We would like to thankDr C D Alergant, Dr E Annels, Dr 0 P Arya and DrF Lancely for allowing us access to their malepatients' case sheets. We are indebted to ProfessorPercival and Dr R E Rewell for microbiologicalinvestigations, to Dr G C Turner for serological testsfor syphilis, to Dr T N Calvey of the Department ofClinical Pharmacology for serum tetracycline estima-tions, and to Mr C R West for help with statisticalanalysis.

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9. Coppleson M, Reid B. Preclinical Carcinoma of the CervixUteri. 1st ed. Oxford: Pergamon Press, 1967.

10. Singer A, Jordan JA. The anatomy of the cervix. In: JordanJA, Singer A, eds. The Cervix. London: WB Sanders 1976:13-36.

I1. Singer A. The cervical epithelium during puberty andadolescence. In: Jordan JA, Singer A, (eds). The Cervix.London: WB Sanders 1976: 87-104.

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