Reproductive tract infections, gynaecological morbidity and HIV seroprevalence among women in Mumbai, India.

Reproductive tract infections, gynaecological morbidity and HIV seroprevalence among women in Mumbai, India L. Brabin,1 A. Gogate,2 S. Gogate,3 A. Karande,4 R. Khanna,5 N. Dollimore,6 K. de Koning,7 S. Nicholas,8 & C.A. Hart9 Reported are the prevalence of reproductive tract infections and their contribution to pelvic inflammatory disease (PID), as well as the seroprevalence of human immunodeficiency virus (HIV), among women living in three inner city wards of Mumbai, India. Women aged s35 years were recruited and screened as cases if they had been admitted to hospital forgynaecological investigation for suspected PID (n = 151) or infertility (n = 295); controls were healthy fertile women attending for laparoscopic tubal ligation (n = 2433). The women were mainly of low socioeconomic status. A total of 59.4% were migrants and 14.9% of these came to Mumbai to seek treatment. Cases reported a history of adverse pregnancy outcomes significantly more often than controls, and 30.5% of suspected PID cases had previously undergone laparoscopic tubal ligation. At examination 24.2% of cases and 8.4% of controls had a vaginal discharge. Pelvic infection was confirmed in 42.0% of suspected PID cases and 14.6% of infertile cases for whom diagnostic laparoscopy was performed. The prevalence of sexually transmitted diseases was low: Chiamydia trachomatis was found in 0.2%; and Neisseria gonorrhoeae was cultured from the cervix in only four cases. Neither of these infections was detected in laparoscopic aspirates. The prevalence of HIV1/2 infections in unlinked samples was 1.9%. Sexually transmitted diseases were not major factors leading to gynaecological morbidity. Heterosexual spread of HIV infection to this population of married women is still relatively low but needs to be carefully monitored. The gynaecological morbidity detected may be a consequence of widespread use of invasive methods of fertility regulation. Introduction Gynaecological morbidity associated with sexually transmitted diseases (STDs) is thought to be high among women in developing countries. Pelvic in- flammatory disease (PID) is one consequence of STD infection and itself may lead to infertility (1). Previous studies have indicated that in India PID was more likely to be obstetric in origin rather than to result from STDs (2). A study of reproduc- tive tract infections among rural Maharashtrian women by Bang et al. in 1989 reported a high preva- lence of signs and symptoms indicative of reproduc- tive tract infections in older women (3). Those observations were made at a time when India was experiencing a rapid rise in reported human immunodeficiency virus (HIV) infections and ac- quired immunodeficiency syndrome (AIDS) cases among commercial sex workers, and there was grow- ing international concern that HIV infection would spread heterosexually to lower-risk populations of women in India (4, 5). Under such circumstances a rise in STDs and PID among these women might also be expected. In order to determine the preva- lence of reproductive tract infections and their contribution to pelvic infection, we carried out a cross-sectional study of Indian women suffering Senior Lecturer, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, England. Requests for re- prints should be sent to Dr Brabin at this address. 2 Professor, Brihan Mumbai Municipal Corporation, Mumbai, India. 3 Consultant Obstetrician, Brihan Mumbai Muncipal Corporation, Mumbai, India. 4 Executive Health Officer, Brihan Mumbai Municipal Corporation, Mumbai, India. Reprint No. 5860 5 Consultant, Brihan Mumbai Municipal Corporation, Mumbai, India. 6 Deceased. Formerly: Lecturer, Liverpool School of Tropical Medicine, Liverpool, England. 7 Lecturer, Liverpool School of Tropical Medicine, Liverpool, England. 8 Research Fellow, Liverpool School of Tropical Medicine, Liver- pool, England. 9 Clinical Consultant and Head, Department of Medical Micro- biology and Genitourinary Medicine, University of Liverpool, Liverpool, England. Bulletin of the World Health Organization, 1998, 76 (3): 277-287 © Word Health Organization 1998 277 L. Brabin et al. from infertility and pelvic inflammatory disease and of controls who were representative of fertile, healthy women. The control group selected con- sisted of women attending for tubal ligation; not only are such women demonstrably fertile, but tubal ligation in India is routinely performed by laparoscopy (6). This provided a unique opportunity to screen apparently healthy women for lower and upper genital tract infection as well as for tubal pa- thology. The first epidemiological results from this study are reported in this article: a detailed analysis of risk factors for pelvic infection has been reported elsewhere (7). Methods Study area and subjects The study was undertaken in Mumbai (formerly Bombay), capital of Maharashtra State, between October 1993 and December 1995, in association with Brihan Mumbai Municipal Corporation (BMC). Mumbai is the industrial, commercial, and financial capital of India and over the last 20 years urbanization and industrialization have led to its rapid growth. The current population is over 10 mil- lion and inner city areas are densely populated. Al- most half of the population lives in slums (huts and one-room tenements (chawls) (8). Since 1988 BMC has sought to extend family health services to all slum areas by creating health posts and postpartum centres offering health education, preventive ser- vices, simple curative care, family planning and legal abortion (medical termination of pregnancy), and laparoscopic sterilization (tubal ligation). Clinical care, including medical termination of pregnancy and tubal ligation, is available free at municipal establishments, although nonscheduled medicines must be paid for. The study women were recruited at three cen- tres located in three neighbouring administrative ar- eas (wards). Most cases were recruited at Lokmanya Tilak Municipal General Hospital (LTMGH) (ward F/N) and most controls from Mahim Maternity Home (ward G/N) and F/S Postpartum Centre (ward F/S). Wards F and G are characterized by the presence of textile mills and tenements. All three wards have large slum areas, although vacant plots have attracted private builders and settlement of middle-class families. LTMGH is a 1304 bed tertiary hospital with a medical school and has six consultant units providing obstetric and gynaecological out- and inpatient care. Mahim Maternity Home is a 60- bed unit, performing 1200 deliveries a year and postpartum services, including tubal ligation. The Postpartum Centre in ward F/S is the city's busiest municipal clinic offering family planning, medical termination of pregnancy, and tubal ligation ser- vices. It is favoured by women because they are not retained for overnight observation after steriliza- tion. Medical termination of pregnancy may be per- formed at the same time as tubal ligation, and at LTMGH and Mahim tubal ligation is often per- formed immediately after delivery. Women were defined as cases if they presented for gynaecological investigations, either with symp- toms of acute pelvic infection (suspected PID) or a history of infertility that might indicate prior salpingitis. Such women were suspected to have a reproductive tract infection- although their precise PID status was not confirmed until after clinical examination and laparoscopy. Excluded were infer- tility cases where an infertile male partner was iden- tified. Women with infertility problems were always requested to bring their partners for tests. Controls were fertile women seeking tubal ligation who had no symptoms of gynaecological disease. Since acute salpingitis patients were likely to be younger than tubal ligation controls, women older than 35 years were excluded from the study. Permission to conduct the study was granted by BMC and ethical approval was obtained from the Ethical Committee of LTMGH and Medical School. Study procedures Questionnaires. Social questionnaire. A total of 30 auxiliary nurse midwives (ANMs) were seconded by BMC to the research project, and trained to enhance their skills in questioning women on their sexual behaviour. The questionnaire was developed with ANMs through a process of careful piloting, asking open-ended questions on predetermined issues, until closed questions with meaningful response catego- ries could be specified. Interviews were conducted in the local languages (Marathi and Hindi) in a sepa- rate, quiet room where confidentiality could be maintained. Interviews were always conducted by two ANMs - one who asked questions, while the other recorded the responses. This procedure al- lowed one ANM to give full and sympathetic atten- tion to the women, while ensuring careful recording of answers. At Mahim and F/S social interviews pre- ceded clinical procedures, and the ANMs explained these procedures and reassured women, who were often fearful. At LTMGH, social interviews were given after the clinical procedures because the hospi- tal was very busy and women waiting to go into the operating theatre could not be interviewed confi- dentially. A disadvantage of this approach was that WHO Bulletin OMS. Vol 76 1998278 Reproductive tract infections among women in Mumbal, India the women, particularly tubal ligation patients, might be discharged before the ANMs interviewed them. The social questionnaire covered the sociode- mography (marital status, religion, migrant history, education, income), contraceptive use, and sexual history of the woman and her partner. Clinical questionnaire. A clinical questionnaire was administered at all centres. This involved six consul- tant units at LTMGH and one consultant unit at Mahim Maternity Centre. The questionnaire cov- ered the reasons for referral, gynaecological history - including menstruation and symptoms of genital and urinary tract infection- and obstetric, medical, and surgical histories. Gynaecological examination. Consultants were brought together to agree on study procedures, and overall supervision was provided by the consultant at Mahim Maternity Centre (S. G.). The vulva was ex- amined for lesions and any vaginal discharge was noted. The cervix was inspected for ulcers, warts, ectopy, and cervicitis - defined as erythema or in- flammation with or without a mucopurulent dis- charge. Three high vaginal swabs were taken: one was placed in TV medium for Trichomonas vaginalis and candida; a second was placed in Amies transport medium for aerobes, anaerobes, and Gardnerella vaginalis; and a third was placed in sterile saline solution for wet mounting and Gram staining. After the ectocervix had been cleaned of secretions, two Dacron-coated swabs were placed in the cervical os and rotated to collect endocervical secretions and cells. These were placed separately in Amies trans- port medium for Gram staining and culture of Neisseria gonorrhoeae, Mycoplasma hominis, and Ureaplasma urealyticum. A third wire swab for anti- gen detection of Chlamydia trachomatis by enzyme- linked immunosorbent assay (ELISA) was collected in Mastazyme transport medium (Mast Laborato- ries, Bootle, England). After removal of the spe- culum, a bimanual examination was carried out to test for rebound tenderness and masses, which were recorded diagrammatically, as well as tender- ness of the fornices and excitation of the cervix. A clinical diagnosis of PID was made when lower abdominal pain and/or tenderness of the fornices, adnexal tenderness, and/or fever were present. After physical examination and before any operative procedure, a 5-ml blood sample was taken for serological tests. At F/S Postpartum Centre, where only control cases were enrolled, transvaginal sonography was performed before all laparoscopic tubal ligations were carried out to rule out any pelvic pathology and to confirm pregnancy in cases of medical termination of pregnancy with tubal ligation. Laparoscopy. Before laparoscopy, routine haema- tological tests (erythrocyte sedimentation rate, white blood cell count, haemoglobin level) were per- formed. Laparoscopy was carried out under general anaesthesia in the usual manner. Acute salpingitis was classified as follows: mild (tubes inflamed but mobile, with no pus observed); moderate (tubes im- mobile and pus present); or severe (pyosalpinx or an abscess present). Chronic pelvic infection was re- corded if there were adhesions around the uterus and adnexa, and/or in the cul-de-sac, with forma- tion of tubal ovarian masses. Prior to any further endoscopic procedures, 20ml sterile saline was in- oculated into the cul-de-sac, sprayed over the uterus, and adnexal areas and aspirated back from the cul- de-sac. If any fluid was already in the cul-de-sac it was aspirated directly and returned to the laboratory for microbiological tests. Although obstetricians were requested to perform laparoscopy for all cases where acute salpingitis was suspected, most were extremely reluctant to so for the most severe cases since it was standard practice to treat such cases immediately without performing laparoscopy. For such cases, culdocentesis was performed, although it was recognized that cul-de-sac specimens obtained by this procedure would be open to interpretation (9), and they are not discussed here. Women with acute salpingitis were immediately started on antibi- otic therapy. Microbiological assessments. Samples were trans- ported to the laboratory at LTMGH within 4 hours of collection. Microscopy. Wet mount microscopy of high vaginal swabs for T. vaginalis was performed immediately on arrival at the laboratory. Gram-stained vaginal smears were examined microscopically for clue cells and white blood cells. Bacterial vaginosis was diag- nosed if >5 clue cells per high power field (X40) were counted and white vaginal discharge had been observed clinically. Gram-stained cervical smears were also used for observation of diplococci, candida and any other microorganisms. Cultures. Aerobes were inoculated into glucose phosphate broth and anaerobes into sodium thioglycollate broth. Gonococcal culture specimens were incubated at 35-37°C in an atmosphere con- taining carbon dioxide (10%) for up to 48 hours on Thayer-Martin medium. Sugar utilization tests were carried out on all oxidase-positive Gram-negative diplococci. G. vaginalis was grown on GV medium under an atmosphere of 95% hydrogen and 5% car- bon dioxide. T. vaginalis specimens were cultured in WHO Bulletin OMS. Vol 76 1998 279 L. Brabin et al. AC medium. Sabouraud's agar was used to culture candida. PPLO broth was used for ureaplasma and mycoplasma, followed by PPLO agar for colonies of M. hominis. All the media were prepared, inocu- lated, and incubated as routine microbiological procedures. Antigen detection and serology. Cervical swabs from all cases and controls for chlamydia antigen were frozen at -40°C until examined by ELISA (Mastazyme; Mast Laboratories, Bootle, England). Antigen detection of C. trachomatis by ELISA was performed on all the cases (suspected PID and infertility) and on every fifth specimen of the aspi- rates collected. All ELISA-positive samples and a subsample of negatives were frozen and returned to Liverpool for polymerase chain reaction (PCR) test- ing. PCR amplification was carried out by using both primers for C. trachomatis major outer membrane protein (MOMP in-house assay) and for the C. trachomatis cryptic plasmid (Roche, Diagnostics Ltd., Welwyn Garden City, Herts, England). Occa- sionally false-negatives arise in PCR detection be- cause of the presence of inhibitory factors (either destroying target DNA or inhibiting taq poly- merase). In order to assess this possibility, 10% of PCR-negative samples were retested after C. trachomatis had been added to them. In each case, C. trachomatis was detected (i.e. no inhibitory factors were detected). Those samples that were positive by ELISA and confirmed by PCR were classified as positive for C. trachomatis. Samples that were posi- tive by ELISA and negative by PCR were classified as negative for C. trachomatis, and similarly all ELISA negatives. The prevalence shown in the Re- sults section was obtained using this classification. Blood samples were tested for syphilis using the Venereal Disease Research Laboratory (VDRL) test in which positive and negative controls were included with each batch. A Treponema pallidum haemaglutination assay (TPHA) was carried out on all positive VDRL samples for confirmation. Un- linked blood samples were tested for HIV 1/2 by ELISA (Wellcozyme 1/2, Dartford, Kent, England). All positive samples were confirmed using a second ELISA (RECOMBIGEN; Cambridge Biotech Corporation, MA, USA) and when positive by both were reported as positive. Patient follow-up. All patients undergoing laparos- copy received doxycycline or ampicillin orally for 5 days during the post-operative period. Those with PID received either cefuroxime or ciprofloxacin along with metronidazole. All the patients were called for follow-up 7-10 days after laparoscopy, at which time laboratory reports were reviewed and those cases with lower genital tract infections as well as control cases found to have PID were given full appropriate treatment. Patients who did not come for follow-up were visited at home by trained ANMs wherever possible. Husbands were requested to come for follow-up advice and treatment, though the response was rather poor. Data analysis. Questionnaire data were entered in dBase III and analysed using STATA software. Dif- ferences in proportions between cases and controls were tested for significance using x2 tests. Fisher's exact test was used for small sample sizes. Results A total of 3588 women were screened, 1746 of whom were recruited at LTMGH Hospital, 886 at Mahim Maternity Home and 954 at F/S Postpartum Centre; for two cases the centre was unrecorded. Women for whom the data were incomplete (576) were excluded from the analysis. A further 133 were excluded be- cause either they were aged >35 years or it was unclear if laparoscopy had been performed. This left a total of 2879 women, 295 of whom were infertile and 151 were suspected PID patients, giving a total of 446 cases. A total of 2433 women attended for tubal ligation and were designated as controls. Alto- gether, 37.9% of tubal ligations were performed with concurrent medical termination of pregnancy, 37.1% followed delivery, and 24.9% were interval sterilizations (i.e. not associated with pregnancy). A total of 86 (3%) women reported taking antibiotics 15 days prior to the clinic visit but as the precise nature and duration of their medication were uncer- tain, they were not excluded from the analysis. Socioeconomic status of the study women The three main religions of the cases and controls were Hinduism (73.8%), Islam (12.3%), and Bud- dhism (10.9%). The mean age of infertility cases was 25.1 ± 4.1 years, that of suspected fertility cases, 25.4 ± 4.6 years and that of tubal ligation patients, 27.0 + 3.6 years. A total of 4.7% of cases and 0.27% of controls were aged <20 years. Altogether, 59.4% of the women were migrants to Mumbai, mostly from other areas of Maharashtra State (34.8%) and Uttar Pradesh (13.7%). Nonmigrants were younger than migrants with the exception of infertility cases, for whom the age distribution was similar: 45.5% versus 43.0% infertile cases were aged <25 years; 42.3% versus 23.2% for suspected PID cases (P = 0.02); and 24.4% versus 12.1% for tubal ligation controls (P < 0.01). In general, migrant cases and controls had fewer years of schooling: 50.8% of migrants WHO Bulletin OMS. Vol 76 1998280 Reproductive tract infections among women in Mumbal, India compared with 26.0% of nonmigrants had <3 years of schooling (P < 0.01). The reasons most often cited by migrants for moving to Mumbai were marriage (47.1%) or family displacement (21.9%), while 14.9% had come to seek treatment. Migrant cases were more likely than migrant controls to have arrived in Mumbai over the previous 5 years (60.5% of cases versus 27.5% of controls); 33.3% of such women had household incomes <1000 rupees per month. Fertility status A total of 98.8% of the study women were married and only 33 reported a previous divorce or widowhood. The mean age (±SD) at marriage was 18.3 ± 3.9 years for infertile women, 18.0 ± 3.3 years for tubal ligation groups, and 17.5 ± 3.9 years for suspected PID cases. Altogether, 75.3% of infertility cases and 13.9% of suspected PID cases had never been pregnant. These groups also had significantly fewer live-born children and reported more preterm pregnancies, stillbirths, and spontaneous abortions than controls (Table 1). The proportion of cases who had undergone at least one medical termination of pregnancy prior to the clinic visit (13.3%) was simi- lar to that among fertile controls (13.0%). In con- trast, 9.1% of infertile women reported having ever used a contraceptive method (oral contraceptive pill, condoms or intrauterine device) compared with 31.8% of suspected PID cases and 53.1% of tubal ligation patients (Table 2). The most widely used method was the copper intrauterine device. Very few women reported use of the safe period or pre- ejaculatory withdrawal, although later in-depth in- terviews of the women (not reported here) found that they did use a number of natural spacing methods - although they were not perceived as such. Of the suspected PID patients, 30.5% reported that they had previously undergone tubal ligation although no information was collected on when this had been performed. Table 1: Outcome of pregnancy among cases and controls who had ever been pregnant Cases Controls Pregnancy outcome No. infertile No. suspected PID Total Tubal ligation P-value Live-bom children (n) 0 30 (41.1)8 11 (8.5) 41 (20.2) 0 (0) 1 31 (42.5) 33 (25.4) 64 (31.5) 22 (0.9) 2 8 (11.0) 45 (34.6) 53 (26.1) 1 040 (42.8) 3 3 (4.1) 24 (18.5) 27 (13.3) 1 036 (42.5) 4 1 (1.4) 16 (12.3) 17 (8.4) 259 (10.6) -_4 0 (0) 1 (0.8) 1 (0.5) 76 (3.1) Total 73 (100) 130 (100) 203 (100) 2433 (100) <0.01 Pre-term deliveries (n)b 0 70 (95.9) 120 (92.3) 190 (93.6) 2 382 (97.9) 1 3 (4.1) 10 (7.7) 13 (6.4) 38 (1.6) >1 0 (0) 0 (0) 0 (0) 5 (0.2) Not known 0 (0) 0 (0) 0 (0) 8 (0.3) Total 73 (100) 130 (100) 203 (100) 2433 (100) <0.01 Still births (n) 0 67 (91.8) 123 (94.6) 190 (93.6) 2376 (97.6) 1 6 (8.2) 7 (5.4) 13 (6.4) 47 (1.9) 1 0 (0) 0 (0) 0 (0) 10 (0.4) Total 73 (100) 130 (100) 203 (100) 2433 (100) <0.01 Spontaneous abortions (n) 0 38 (52.1) 116 (89.2) 154 (75.9) 2279 (93.7) 1 25 (34.2) 8 (6.2) 33 (16.3) 128 (5.3) >1 10 (13.7) 6 (4.6) 16 (7.9) 26 (1.1) Total 73 (100) 130 (100) 203 (100) 2433 (100) <0.01 MTP (n)c 0 67 (91.8) 109 (83.8) 176 (86.7) 2 117 (87.0) 1 5 (6.8) 18 (13.8) 23 (11.3) 263 (10.8) >1 1 (1.4) 3 (2.3) 4 (2) 53 (2.2) Total 73 (100) 130 (100) 203 (100) 2433 (100) 0.96 a Figures in parentheses are percentages. b <37 weeks. c Medical termination of pregnancy. WHO Bulletin OMS. Vol 76 1998 281 L. Brabin et al. Table 2: Distribution of contraceptive use among cases and controls Cases Controls Infertile Suspected PID Total Tubal ligation Ever used/had: (n = 295) (n = 151) (n = 446) (n = 2433) P-value Oral contraceptive pill 8 (2.7)a 5 (3.3) 13 (2.9) 283 (11.6) <0.01 Condoms 11 (3.7) 18 (11.9) 29 (6.5) 429 (17.6) <0.01 Copper (IUD) 8 (2.7) 25 (16.6) 33 (7.4) 581 (23.9) <0.01 Tubal ligation 5 (1.7) 46 (30.5) 51 (11.4) 0 (0) <0.01 a Figures in parentheses are precentages. Clinical status have clinical pelvic infection after bimanual exami- nation. All women were referred for diagnostic History and symptoms. History and symptoms con- laparoscopy or, if the symptoms were very acute, for sistent with a genitourinary infection were reported culdocentesis (143 cases). significantly more often by cases, particularly by women with suspected PID (Table 3). Vaginal dis- Laparoscopy results. The results of laparoscopy are charge and pain during intercourse were the symp- shown in Table 4. A total of 26 women had acute toms registered most often by all cases (21.7% and salpingitis and 48 chronic pelvic infection. A diagno- 26.4%, resp.), with suspected PID patients exhibiting sis of PID was confirmed in 42.0% of women with lower abdominal pain, either between or during suspected PID but in only 14.6% of infertile patients. menstrual episodes. A history of tuberculosis was reported by 7.2% of infertile and 5.3% of suspected Microbiological results PID cases, compared with 1.4% of controls. Vaginal infections. The number of women with Gynaecological examination. No warts or ulcers symptomatic candidosis and trichomoniasis was very were observed on inspection of the vulva and cervix. low (Table 5). Bacterial vaginosis was detected in The proportion of woman with vaginal discharges 6% of women with suspected PID. For women in reported by clinicians was similar to that reported by whom bacterial vaginosis was detected, G. vaginalis the women themselves (24.2% for cases and 8.4% was present in 13.6% compared with 7.9% of those for controls; P < 0.01). Cervicitis was described without bacterial vaginosis (P = 0.32). Presence or for 6.0% of cases (11.3% of those with suspected absence of bacterial vaginosis was examined in rela- PID) and 1.8% of controls (P < 0.01). Of the tion to "ever" having used contraceptive methods, suspected PID cases, 74.8% were considered to but no association was found. Table 3: Clinical history and symptoms reported by cases and controls Cases Controls No. infertile No. suspected PID Total No. with tubal ligation P-value HistoryofSTD 0/291 (0)- 11/149 (7.4) 11/440 (2.5) 1/2418 (0.1) <0.01 Had PID symptoms beforeb 2/295 (0.7) 13/151 (8.6) 15/446 (3.4) 0/0 (0) History of tuberculosis 21/293 (7.2) 8/150 (5.3) 29/443 (6.5) 33/2 425 (1.4) <0.01 Partner infection 19/289 (6.6) 17/140 (12.1) 36/429 (8.4) 111/2 393 (4.6) <0.01 >1 infections reported Any pains related to menstruation 23/295 (7.8) 36/151 (23.8) 59/446 (13.2) 57/2 433 (2.3) <0.01 Lower abdominal pain outside 5/295 (1.7) 81/151 (53.6) 86/446 (19.3) 8/2 433 (0.3) <0.01 menstruation Frequent urination with lower 0/295 (0) 22/146 (15.1) 22/441 (5.0) 1/2 431 (0) <0.01 abdominal pain Vaginal discharge 27/295 (9.2) 70/151 (46.4) 97/446 (21.7) 126/2 433 (5.2) <0.01 Irritation/itching 3/295 (1.0) 20/151 (13.3) 23/446 (5.2) 22/2433 (0.9) <0.01 Pain during intercourse 64/294 (21.8) 53/150 (35.3) 117/444 (26.4) 159/2 428 (6.5) <0.01 a Figures in parentheses are percentages. b Only suspected cases asked. WHO Bulletin OMS. Vol 76 1998282 Reproductive tract infections among women in Mumbal, India Table 4: Distribution of diagnostic laparoscopy findings Cases Controls Finding No. infertile No. with suspected PID Total No. with tubal ligation Acute salpingitis Mild 4 (1.5)a 4 (8.0) 8 (2.6) 1 (0) Moderate 6 (2.3) 6 (12.0) 12 (3.9) 2 (0.1) Severe 0 (0) 2 (4.0) 2 (0.6) 1 (0) Chronic PID 28 (10.7) 9 (18.0) 37 (11.9) 11 (0.5) No PID 223 (85.4) 29 (58.0) 252 (81) 2410 (99.4) Total 261 (100) 50(100) 311 (100) 2425 (100) a Figures in parentheses are percentages. Cervical and upper genital tract infections. M. Serological findings. A total of 4.1% of infertile hominis and U. urealyticum were the cervical organ- women were positive for syphilis compared with isms most frequently cultured, with the prevalence of 2.8% of controls (Table 5). Altogether 3372 samples M. hominis being higher in cases (8.3% versus 5.6%) were tested anonymously for HIV 1/2 and 63 (1.9%) and that of U. urealyticum, higher in controls (22.0% were positive. versus 15.8%). From controls, four isolates of N. gonorrhoeae were made from the cervix but none from laparoscopic aspirate. Among controls the Discussion prevalence of C. trachomatis infection (positive by both ELISA and PCR) was 0.2% from cervical This study demonstrates that STDs did not make a specimens and zero in laparoscopic aspirates. A major contribution to reproductive morbidity or PID number of aerobic and anaerobic bacteria were de- in the study population of Indian women. The sensi- tected in cul-de-sac samples, but their prevalence tive culture and PCR techniques that were used was similar for cases and controls. detected only a low prevalence of genital tract infec- Table 5: Distribution of reproductive tract infections among cases and controls Cases Controls No. infertile No. with suspected PID Total No. with tubal ligation P-value Vaginal infections Symptomatic candidosis 1/295 (0.3)a 3/151 (2.0) 4/446 (0.9) 1/2 432 (0) <0.01b Trichomonas vaginalis 1/295 (0.3) 1/151 (0.7) 2/446 (0.5) 22/2 433 (0.9) 0.57b Gardnerella vaginalis 29/294 (9.8) 19/151 (12.6) 48/445 (10.8) 180/2 431 (7.4) 0.02 Bacterial vaginosis 1/295 (0.3) 9/151 (6.0) 10/446 (2.2) 12/2 433 (0.5) <0.01 Cervical infections Neisseia gonorrhoeae 0/295 (0) 0/151 (0) 0/446 (0) 4/2 430 (0.1) 1.Qb Mycoplasma hominis 25/295 (8.5) 12/151 (7.9) 37/446 (8.3) 137/2426 (5.6) 0.03 Ureaplasma urealyticum 43/292 (15.0) 27/150 (18.0) 70/442 (15.8) 533/2 424 (22.0) <0.01b Chlamydia trachomatis 1/286 (0.3) 1/145 (0.7) 2/431 (0.5) 4/2 377 (0.2) 0.23b Aspirates N. gonorrhoeae 0/234 (0) 0/42 (0) 0/276 (0) 0/2 295 (0) M. hominis 0/232 (0) 0/42 (0) 0/274 (0) 2/2264 (0.1) 1.Qb U. urealyticum 2/230 (0.9) 0/41 (0) 2/271 (0.7) 29/2 260 (1.3) 0.78b C. trachomatis 0/197 (0) 0/34 (0) 0/231 (0) 0/1 028 (0) Aerobes: Staphylococcus aureus 1/234 (0.4) 0/42 (0) 1/276 (0.4) 25/2 280 (1.1) 0.35b Streptococcus 0/234 (0) 0/42 (0) 0/276 (0) 0/2 280 (0) - Other 45/234 (19.2) 10/42 (23.8) 55/276 (19.9) 494/2 280 (21.7) 0.59 Anaerobes 0/191 (0) 1/28 (3.6) 1/219 (0.5) 0/1 882 (0) 0.1b Blood Syphilis 12/295 (4.1) 1/151 (0.7) 13/446 (0.5) 67/2 433 (2.8) 0.85 a Figures in parentheses are percentages. b Fishers exact test. WHO Bulletin OMS. Vol 76 1998 283 L. Brabin et al. tions. Reproductive tract infections (RTIs) such as candidiasis were expected to be more common in view of the poor socioeconomic background of the women and the unsatisfactory housing conditions under which many of them lived. The study design required recruitment of women who were eligible for laparoscopy and who were attending a health facility. Like antenatal attenders - a population routinely used as a reference point for STD preva- lence in the general population of women - the study women presented at the health facility for rea- sons other than STD infection. Although there may be subgroups of women among whom the preva- lence of STDs is higher, cultural norms in India are conservative and women are not expected to have sexual relations before marriage or extramaritally. The results of this study suggest that many women adhere to these values; women who do not risk rejec- tion by society and may be obliged to adopt a life- style that makes them more vulnerable to STDs and various degrees of involvement in commercial sex work. The low prevalence of genital tract infections in our study contrasts with the findings of Bang et al. (3) in a population-based study in rural Maharashtra, where women did not have access to good health facilities. Apart from sample selection, the two stud- ies used different criteria to measure STD preva- lence and related morbidity. On clinical grounds, for example, Bang et al. classified 24.2% of women as having PID. If only 40% of suspected cases were confirmed by laparoscopy, as in our study, this proportion would be reduced to about 10%. The difficulties of comparing studies is exemplified by a recent rural, population-based survey of RTIs in Bangladesh, where only 1.1% of women were culture-positive for N. gonorrhoeae and no women had syphilis as defined by a positive TPHA (10). Less stringent criteria, however, were used to define other RTIs and the overall prevalence of RTIs was calcu- lated to be 56.1%. For example, in Bangladesh but not in Mumbai, women were classified as having "nonspecific vaginosis", as distinct from bacterial vaginosis based on the presence of 10 poly- morphonuclear leukocytes and/or Gram-negative bacilli in a high vaginal swab or smear (11). In Bangladesh 9.0% of RTIs were defined on this basis, although trichomoniasis, an infection in which white blood cells may be detected, was found in only 0.3% of women by microscopy. In Mumbai, candidosis, defined as an acute candidal infection in sympto- matic women, was found in < 1% of women; how- ever, had its prevalence been based on the number of women with hyphae or spores on a Gram stain, 7.2% would have been classified as having candidosis, a level comparable to that found in Bangladesh (9.0%). Virtually all the procedures used to measure RTI/STDs differed in the two studies. If the criteria applied in Bangladesh had been applied in Mumbai, it is likely that at least 50% of women in our study would have been registered as having an RTI. As more studies are conducted on RTIs in women, it will be important to standardize the definitions used and to recognize the limitations of interpretation of nonspecific laboratory tests if resources are to be allocated wisely for management of STDs. Interpretation of the HIV seroprevalence data also presents difficulties. An HIV seroprevalence of 1.9% compares well with the results of the first round of sentinel surveillance in 1994 among antenatal clinic attendees in Mumbai, which found an HIV seroprevalence of 2.5% (12). It is of considerable importance to monitor the rate of increase in HIV positivity among low-risk populations of women, since among commercial sex workers in India this rose from 0.9% in 1987 to >40% by 1992 (5), and was more recently reported to be 47.7% (13). The expectation is that the HIV epidemic in India will rapidly spread to lower risk groups (14,15). This was the conclusion of a study of 2800 people attend- ing STD clinics in Pune, which found an HIV seroprevalence of 23.4% among women (16). The prevalence of HIV-1 among 222 women who were not sex workers, 13% of whom claimed to be monogamously married, was 14%. If HIV has truly begun to affect lower risk groups in India, it may reach the same epidemic proportions as are cur- rently observed in some parts of sub-Saharan Africa, where the seroprevalence may be as high as 30% among antenatal clinic attendees (17). None the less, a variety of factors could influence the course of the epidemic. The results of the present study are important because they imply that the number ofwomen whose husbands visit commercial sex workers is relatively small, since otherwise a higher prevalence of HIV infection or cervical infections such as gonorrhoea would probably have been transmitted to their spouses. Alternatively, but less likely, is that the hus- bands visit sex workers but use condoms to protect themselves from infection. This is not to say that the men do not have extramarital affairs, but these rela- tionships may not be with women at high risk of STDs/AIDS. Several Indian studies have demon- strated that the main risk factor for HIV infection is contact with commercial sex workers (18, 19). Al- though many men in Mumbai are migrants, a large proportion live with their families, unlike some cat- egories of migrants such as truck drivers who may be at far higher risk of spreading HIV infection (20). Mehendale et al. observed that patients attending STD clinics and who lived with their families were WHO Bulletin OMS. Vol 76 1998284 Reproductive tract infections among women in Mumbal, India significantly less likely to seroconvert and become HIV positive (21). Of interest in this regard is an Indian study linking men's sexual behaviour to the risk of cervical cancer among their sexual partners. Agarwal et al. found that the husbands of monoga- mous women with persistent dysplasia were more likely than controls to have had premarital and ex- tramarital sex, and to have resumed sexual activity with their wives before 40 days' postpartum (22). Conversely, no correlation was found between hus- bands' sexual activities with prostitutes and cervical cancer among their wives. This contrasts with the results of a study in Thailand that found no associa- tion between a woman's risk of cervical cancer and her husband's total number of sexual partners or with the number of his extramarital partners other than prostitutes (23). The association with cervical cancer was significantly higher only for women whose husbands had a first encounter with a prosti- tute in their teens or twenties. Hence, understanding the characteristics of men who visit commercial sex workers - as well as other types of premarital and extramarital relationships practised by men - is essential if targeted and relevant intervention and education strategies are to be promoted to prevent gynaecological morbidity and spread of HIV infection. Finally, most women with suspected PID did not have evidence of RTIs. Women with the most acute symptoms of PID were not referred for laparoscopy but there was no evidence to suggest a higher prevalence of lower tract infection in this group (24). Of those women presenting with pelvic pain characteristic of salpingitis, 30.5% had under- gone previous laparoscopic sterilization, and 13.9% medical termination of pregnancy. In India many women rely on invasive methods of fertility regula- tion such as tubal ligation, IUDs and medical termi- nation of pregnancy, and a recent survey confirms that the reproductive span of many women has been artificially shortened to a mean of 10 years (25). In our study most women married at about 18 years of age and had been sterilized by 27 years of age, al- though 17.2% had elected for tubal ligation by the age of 24 years. Typically, the study women had had several pregnancies and medical terminations of pregnancy, had experimented with an IUD, and then sought tubal ligation. A total of 37.9% of all the tubal ligations were performed with concurrent medical termination of pregnancy - a striking demonstra- tion of widespread acceptance of termination of pregnancy. There are several risks inherent in this strategy for limiting family size. If lower tract infec- tions such as bacterial vaginosis are present, women undertaking medically invasive procedures may be at increased risk of reproductive morbidity (26). There may also be surgical complications arising from such procedures (27). In a study by Keith et al. (28), despite the claimed safety of the procedure, hypotension occurred in 39 of 167 cases undergoing laparoscopic sterilization during puerperium. There are also likely to be psychosocial consequences re- sulting from such a dramatic shortening of the nor- mal reproductive span. A total of 8.2% of the study women who were seeking treatment for secondary infertility had previously undergone a medical termi- nation of pregnancy and 1.7% a previous tubal ligation. Their current treatment-seeking behaviour would seem to suggest that they had changed their minds about the desirability of pregnancy, as ob- served in other studies (29). Although women were not asked their reasons for choosing irreversible methods of fertility control, it is likely that increased education, intense pressure on living accommoda- tion, convenience of the method, and regular expo- sure to messages encouraging sterilization were all factors that influenced them. However, the long-term psychological, physical, or economic effects on individual women who termi- nate their reproductive lives at such an early stage have been little investigated. In recent years atten- tion has focused on STD-related gynaecological morbidity amid concern to uncover the hidden prob- lem of RTIs in women. Perhaps now is the time to widen this perspective and to focus more attention on women who do not necessarily have RTIs but who may suffer because of the growing acceptance that liberal use of invasive medical procedures pro- motes reproductive health. Acknowledgements The research reported in this article was carried out by the Brihan Mumbai Municipal Corporation and the Population and Reproductive Health Programme, Liverpool School of Tropical Medicine. The study on pelvic inflammatory disease was funded by the Overseas Development Administration of the United Kingdom. The Overseas De- velopment Administration accepts no responsibility for any information provided or views expressed. A supplemen- tary grant was received from the WHO Global Programme on AIDS for determination of the seroprevalence of syphi- lis and of HIV. Many people contributed to the success of this study and for all their help we are grateful. We wish specifically to thank Dr S. Desmukh, Dean, LTMGH, for facilitating work at the hospital, and all those who contrib- uted to the clinical, laboratory and social and data man- agement teams in India. In Liverpool we thank Dr W. Tong for PCR testing of chlamydia samples in his laboratory. We also wish to acknowledge the constant help of Mr B. Shackleton and finally, posthumously, Ms N. Dollimore, who helped set up the study, but who was tragically killed before seeing its conclusion. WHO Bulletin OMS. Vol 76 1998 285 L. Brabin et al. Resume Infections genitales, morbidite gynecologique et seroprevalence du VIH chez des femmes de Mumbal, Inde On estime que la morbidite gynecologique associ6e aux maladies sexuellement transmissibles (MST) est elevee dans les pays en developpement. Les infections genitales hautes (pelvic inflammatory disease ou PID) sont l'une des consequences des MST et peuvent conduire a la sterilite. Des etudes r6alisees en Inde avaient deja indique que les PID 6taient plus probablement d'origine obstetricale que consecutives a une MST. La presente etude avait pour objectif de determiner la prevalence des infec- tions genitales et leur contribution aux PID, ainsi que la prevalence des infections a VIH, chez les femmes consultant des centres de sante dans trois secteurs administratifs de Mumbai (anciennement Bombay). Les femmes de s35 ans ont ete recrutees comme cas lorsqu'elles etaient admises a l'h6pital pour une suspicion d'infection genitale haute (n = 151) ou de sterilite (n = 295), et le groupe t6moin etait constitue de femmes fecondes en bonne sante venues a l'h6pital pour une ligature des trompes par laparoscopie (n = 2433). Ces femmes etaient pour la plupart de faible niveau socio-6conomique; 59,4% etaient des immigrees et 14,9% 6taient venues a Mumbai pour y recevoir un traitement. Les cas mentionnaient plus souvent des ant6c6dents d'issue defavorable de la grossesse que les temoins. Parmi les cas de suspicion de PID, 30,5% avaient deja eu une ligature des trompes par laparoscopie. A l'examen, 24,2% des cas et 8,4% des temoins avaient un ecoulement vaginal. L'infection pelvienne a ete confirm6e chez 42,0% des cas suspects de PID et chez 14,6% des femmes st6riles ayant fait l'objet d'une laparoscopie diagnostique. La prevalence des maladies sexuellement transmissibles 6tait faible. Chlamydia trachomatis a ete trouv6 chez 0,2% des cas et Neisseria gonorrhoeae n'etait present dans les cultures de pr6l6vements cervicaux que dans 4 cas. Aucun de ces germes n'6tait pr6sent dans les prelevements effectu6s par laparoscopie. La pr6valence des infections par le virus de l'immunod6ficience humaine 1 ou 2 (VIH 1/2) dans les 6chantillons anonymes etait de 1,9%. L'etude montre que les MST ne contribuent pas de facon importante a la morbidite due aux infections genitales hautes dans cette population. De nombreuses femmes subissent des interventions invasives comme la laparoscopie et l'interruption volontaire de grossesse, qui comportent par elles- memes un risque de complications et qui peuvent etre associees a un risque accru de morbidite en cas d'infection genitale basse. L'absence de d6tection d'autres MST chez ces femmes et la pr6valence relativement faible de la seropositivite vis-a-vis du VIH semblent indiquer que le nombre de maris qui fr6quentent des prostitu6es est faible dans cette population. References 1. Germain A et al., eds. Reproductive tract infections. Global impact and priorities for women's reproductive health. New York, Plenum Press, 1992. 2. Belsey MA. The epidemiology of infertility- a review with particular reference to sub-Saharan Africa. Bulle- tin of the World Health Organization, 1976, 54: 319- 341. 3. 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