Chlamydia trachomatis and Neisseria gonorrhoeae are the most prevalent bacterial sexually transmitted infections (STIs) worldwide. The incidence of these infections is high in sub-Saharan Africa, with more than 10 million new chlamydial and 17 million new gonococcal infections annually, as estimated by the World Health Organization.1 The burden of STIs in South Africa is estimated to be 20% greater in women than in men.1,2 Various factors contribute to the vulnerability of African women for STI: economic dependency on men, inability to negotiate condom use, concurrent sexual relationships, engagement in transactional sex for survival, nonspecific clinical symptoms, and poor knowledge of and access to STI treatment services, particularly in rural settings.2
Chlamydial and gonorrheal infection may occur at any anatomical site of sexual contact including the endocervix, urethra, rectum, and oropharynx.3 Symptoms may occur after infection approximately, but most chlamydial and gonococcal infections in women remain asymptomatic.3,4 Unrecognized and untreated infections may result in long-term complications such as infertility, chronic pelvic or rectal pain, increased risk of ectopic pregnancy, and spontaneous abortion.5,6
Most European countries and the United States have implemented STI control programs that vary from case management to opportunistic screening of high-risk groups.7 South Africa has implemented a protocol of syndromic management of STI including a partner notification system.8 This means that women presenting with vaginal discharge syndrome (VDS) or lower abdominal pain syndrome (pelvic inflammatory disease) are treated with a combination of broad-spectrum antibiotics without diagnostic tests. The combination of antibiotics that is given is effective against most of the pathogens associated with each syndrome, both STIs and non-STIs. However, women who do not experience physical complaints of chlamydial and gonococcal infections remain largely untreated and are therefore at risk for long-term sequelae and may contribute to continuous transmission of infection.5
A recent systematic review of the prevalence of chlamydia and gonorrhea in women attending antenatal care (ANC) estimated a mean prevalence of 6.9% for chlamydia and 3.7% for gonorrhea in women in East and Southern Africa.9 However, this analysis did not include data from South Africa and was specifically focused on women attending ANC. Data on chlamydial and gonococcal infections in South Africa are limited and have been largely focused around prevalence in urban settings and determination of the microbial aetiology of VDS.10–12 Information on the prevalence, manifestations, and risk factors of genital infections in women living in rural areas is limited. In addition, we are not aware of any recent prevalence data on rectal or pharyngeal chlamydia or gonorrhea in African women.
To obtain insight into the burden of disease, we conducted a cross-sectional study of vaginal, rectal, and oral chlamydial and gonococcal infections in women visiting primary health care (PHC) clinics for any indication in rural South Africa.
MATERIALS AND METHODS
Study Population and Design
This cross-sectional study was conducted at 25 of the 100 PHC facilities across Mopani District, South Africa. The number of participating facilities in each subdistrict was proportional to the population size of each subdistrict; facilities were selected within each subdistrict based on geographic location and size of catchment population. We visited each PHC facility once, on a random weekday, for consecutive sampling of participants from November 2011 to February 2012; 5 facilities were visited twice to reach the targeted number of 600 inclusions. Group information was provided in the waiting area followed by individual counseling of women who were interested. All women aged 18 to 49 years who reported to have been sexually active during the last 6 months were eligible regardless of the reason for visiting the clinic that day. Exclusion criteria were refusal to have tests taken from all 3 anatomical sites (i.e., vagina, anorectum and oropharynx) and having menses on day of recruitment. Patient information was provided and written consent was obtained. The study was approved by the Human Ethics Research Committee of the University of the Witwatersrand, South Africa (Ref. M110726).
Study Procedures
After informed consent, a questionnaire was administered and physical examination was conducted. Self-reported information on HIV status of the participant and her partner was recorded. HIV testing was offered routinely, but this was conducted by clinic staff and results were not collected for this study because of logistic challenges. We obtained swabs (Copan Diagnostics, Brescia, Italy) from the vagina, anorectum, and oropharynx to test for chlamydial and gonococcal infection. Vaginal and rectal swabs were obtained by blindly introducing the swab approximately 5 cm into either the vagina or the anorectum using a rotation movement and sampling the walls when taken out. Pharyngeal swabs were obtained by wiping the swab twice of each lateral posterior wall including tonsillar crypts followed by once across the pharyngeal arc.
Laboratory Tests
Samples were tested for the presence of C. trachomatis and N. gonorrhoeae DNA using the CE-IVD certified PrestoPluS CT-NG-TV assay (Goffin Molecular Technologies, Beek, the Netherlands). This test has been compared previously with the Cobas 4800 CT/NG test (Roche Diagnostics, Indianapolis, IN), COBAS Amplicor (Roche), and the Lightmix Kit 480 HT CT/NG (TIBMOLBIOL, Germany) showing comparable sensitivity, specificity, and positive (PPV) and negative predictive values (unpublished data for N. gonorrhoeae).13 All anorectal samples with positive amplification result for C. trachomatis DNA were tested with real-time polymerase chain reaction for lymphogranuloma venereum and simultaneously for the L2b variant as described elsewhere.14,15
Clinical Definitions
We defined a positive test result of the vaginal swab as genital infection; report of abnormal vaginal discharge, intermenstrual bleeding, and per vagina blood loss during or after sexual intercourse were defined as symptoms of genital infection. Excessive vaginal discharge observed on examination was considered a clinical sign of genital infection. Rectal infection was defined symptomatic if anorectal pain, anal discharge or itch was reported. Pharyngeal infection was considered symptomatic in participants with sore throat and pharyngeal inflammation or tonsillar redness observed on examination.
Data Analysis
Data were double-entered in Epi Data (Epi Info version 3.5.3) and analyzed using SPSS version 13.0 (SPSS Inc, Chicago, IL). Dichotomous data are compared using χ2 test or Fisher exact test, and continuous data using the Mann-Whitney U test. Odds ratio (OR) with 95% confidence interval (CI) are provided. Sensitivity, specificity, PPV, and NPV with 95% CI of clinical symptoms for chlamydia and gonorrhea infection were calculated using a standard 2 × 2 table. Univariate analysis was performed to examine the possible association of risk factors with chlamydia and gonorrhea infection. Multivariate analysis was conducted, with the final model being selected using a forward selection procedure and likelihood ratio tests. We only included variables with a P value less than 0.1 in univariate analysis, except for information about steady partner, plus age and HIV status, as these are known to be associated with chlamydia and gonorrhea.
RESULTS
Characteristics of Study Population
We recruited a total of 604 women in this study. Median age of women was 30 years (range, 18–49 years), and 31% reported to be HIV infected (Table 1). Most women (n = 569; 94%) reported having a steady sexual partner and 69 (12%) occasional partner(s); 89 (15%) reported concurrent sexual partners during the past 12 months (Table 2). Fellatio was reported by 80 women (14%) and receptive anal intercourse (RAI) by 26 (4.6%).
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TABLE 1: Demographic Characteristics and Medical history of Study Population (n = 604)
TABLE 2: Characteristics of Sexual Behavior Reported by Women in Mopani District (n = 604)
Prevalence of Chlamydia and Gonorrhea Infection
Microbiological results were available for 603 of 604 women: results from 1 patient’s swabs were repeatedly indeterminate; this patient was excluded from further analysis. One hundred forty-nine women (25%; 95% CI, 21%–28%) were diagnosed as having STI at any anatomical site: 18% (95% CI, 15%–21%) had chlamydial infection and 11% had gonorrhea (95% CI, 8.6%–14%) at the genital, or rectal, or pharyngeal site. Detection of C. trachomatis per anatomical site was as follows (Fig. 1): genital, 16% (95% CI, 13%–19%), rectal, 7.1% (95% CI, 5.1%–9.1%), and 1 (0.2%) case of pharyngeal infection. None of the rectal C. trachomatis strains was positive for lymphogranuloma venereum or for the L2b serovar. Positive test results for N. gonorrhoeae were obtained for vaginal samples in 10% (95% CI, 7.6%–12%) and 2.5% (95% CI, 1.3%–3.9%) of anorectal samples; none of the oropharyngeal samples tested positive. Infection was limited to the rectum in 11 (26%) of 43 women with rectal chlamydia and 6 (40%) of 15 women with rectal gonorrhea; concurrent genital infection was present in 74% and 60% of women, respectively. Single-site rectal infection was not associated with reporting RAI: only 1 woman of the 26 reporting RAI had rectal infection.
Figure 1: Prevalence of chlamydia and gonorrhea infection by anatomical site in African women. Bars show prevalence with 95% CI of chlamydial (dark gray) and gonococcal (light gray) infection.
Clinical Manifestation of Infection
Information on clinical presentation was available for 592 women (98%), of whom 210 (35%) reported symptoms of genital infection and 164 (27%) had excessive vaginal discharge observed during examination; 278 (47%) had symptoms and/or signs. Seventy-one women (12%) reported symptoms of rectal infection, and 6 (1.0%) had symptoms and signs of oral infection. Symptoms were reported by 26 (28%) of 93 women with genital chlamydial and 18 (31%) of 58 women with gonococcal infection. When symptoms and signs were combined, 39% and 43%, respectively, had clinical manifestations of genital chlamydia or gonorrhea. The PPV of symptoms was low: 12% and 8.6% for genital chlamydial and gonococcal infection, respectively (Table 3).
TABLE 3: Validity of Symptoms and Signs for Indicating Genital and Rectal Chlamydial and Gonorrheal Infection in African Women
Risk Factors for Chlamydia and Gonorrhea
Several crude risk factors for genital and/or rectal chlamydial infection were identified including age, being single, unemployed status, using hormonal contraceptives, current pregnancy, and history of VDS (Table 4). The only variable associated with genital gonorrhea was intravaginal cleaning (OR, 1.9; 95% CI, 1.1–3.4, P = 0.024); age (P = 0.007) and having experienced sexual contact by force (OR, 5.8; 95% CI, 1.2–28; P = 0.028) were associated with rectal gonorrhea, and there was a trend for concurrent sexual partners (OR, 3.0; 95% CI, 0.999–9.0; P = 0.056).
TABLE 4: Univariate Analysis of Risk Factors for Genital and Rectal Chlamydial Infection in African Women
In multivariate analyses (Table 5), age was independently associated with both genital and rectal chlamydia (adjusted OR [aOR], 0.96 [95% CI, 0.93–0.98; P = 0.002] and 0.96 [95% CI, 0.93–0.99; P = 0.003], respectively) as well as rectal gonorrhea (aOR, 0.91; 95% CI, 0.84–0.98; P = 0.014), whereas intravaginal cleansing was associated with genital chlamydial (aOR, 1.7; 95% CI, 1.04–2.8; P = 0.036) and gonorrheal infection (aOR, 1.9; 95% CI, 1.1–3.3; P = 0.029). Pregnancy (aOR, 2.4; 95% CI, 1.3–4.4; P = 0.005) and hormonal contraceptives (aOR, 2.2; 95% CI, 1.3–3.7; P = 0.002) were only associated with genital chlamydia; experience of force was associated with rectal gonorrhea (aOR, 5.0; 95% CI, 1.01–25; P = 0.049).
TABLE 5: Multivariate Analysis of Risk Factors of Genital and Rectal Chlamydia and Gonorrhea in African Women
DISCUSSION
This study is one of only a few to report on the burden of bacterial STI in asymptomatic African women and the first to assess the prevalence of rectal and pharyngeal infection by molecular testing. We observed a high prevalence of genital chlamydial infection (16%) and gonorrhea (10%), which is higher than reported in most studies from sub-Saharan Africa.12,16–19 A slightly higher prevalence of chlamydia (29%) and gonorrhea (14%) has been reported for rural communities in Lesotho and Mozambique, respectively, but study population and setting were different.20,21 Various factors may contribute to the high prevalence of STI observed in our study: first, socioeconomic status and traditional beliefs may play a role; unemployment was associated with chlamydia infection.22 The high proportion of women in our study reporting sexual coercion during the past 6 months is of note. Coercion reflects sex inequality in relationships and is associated with increased sexual risk.23 Second, selective inclusion of women with STI-related symptoms or at increased risk of STI may have occurred as suggested by the relatively high proportion of symptomatic women. However, prevalence of infection was similar among symptomatic and asymptomatic women, and the study population is representative of the normal clinic population. Also, lack of awareness and information as well as poor uptake of partner notification and subsequent treatment may contribute to poor clinical outcome and frequent reinfection. Finally, the low condom uptake reported in this study is a reason for concern and likely contributes to the high prevalence and sustained transmission of chlamydia and gonorrhea in our district.
Rectal chlamydia (7.1%) and gonorrhea (2.5%) were diagnosed in a considerable proportion of women, but only few reported having RAI. The observed prevalence is in similar range to the one reported for chlamydial (4.7–8.7%) and gonorrheal (1.7%) infections detected by molecular tests in women from the United States and the Netherlands.3,24 One study conducted more than 3 decades ago showed a 4.8% prevalence of rectal gonorrhea by bacterial culture in women in South Africa.25 Approximately one-third of rectal infections occurred solely in the rectum. Underreporting of RAI, associated with rectal infection, may have occurred because this practice is considered cultural taboo in our region. Data from Cape Town suggest a 10% prevalence of RAI in heterosexual women compared with less than 5% reported in our study.26 Furthermore, auto-inoculation of the rectum through cervicovaginal fluids is likely to play a role and may result from genital wiping techniques, poor personal hygiene, using fingers during sex or for cleansing afterward, and use of sex toys (although this behavior was not reported by any of the women). On the other hand, because of close anatomical proximity, the possibility that cervicovaginal fluid as contamination is detected instead of true infection of the rectal mucosa cannot be ruled out, despite using clear procedures for sampling. Third, rectal infection may have occurred through sexual contact with the anus but without penetration. When we counseled women with rectal infection, some of them explained that they practice sex, whereby the partner rubs his penis and sometimes ejaculates between the gluteal folds without penetrating the anus. This practice may or may not follow vaginal intercourse and is sometimes used as a method of family planning. To our knowledge, there are no data to support transmission of STI through this type of sexual behavior, but this route of transmission is not unlikely.
We diagnosed only 1 woman with pharyngeal chlamydial infection in our study, and of note, there were no cases of pharyngeal gonorrhea. This is consistent with the low prevalence (0–2%) reported for pharyngeal infection in women from non-African countries.3,27 Although underreporting of fellatio may occur for same reasons as for RAI, pharyngeal infections are unlikely to contribute significantly to the burden of STI in our district.
Most women with chlamydia and gonorrhea did not report any symptoms in our study, whereas most women reporting symptoms did not have any chlamydial or gonococcal infection. As such, most infections would remain untreated if symptoms alone are used to screen and treat women for STI. This confirms data from South Africa and Botswana showing a limited predictive value of clinical symptoms for chlamydial and gonococcal infection questioning the validity of a syndromic approach for STI control.28,29 Unrecognized infection puts many women at increased risk for long-term complications and contributes to a continuously high rate of transmission in the population.7 Further research is warranted to design STI control strategies that do not only include women with symptoms of infection but also target those at high risk for asymptomatic disease.30 Based on the risk factors identified in our study, important groups to prioritize in that regard would be young women and those who are pregnant or using hormonal contraceptives. Age is a risk factor through higher number of sexual partners, higher frequency of sexual intercourse, and increased frequency of occasional sex by younger than older women.31 The increased risk for chlamydial infection associated with hormonal contraception and pregnancy can be attributed to lower condom uptake by these groups, but biological factors related to endocervical susceptibility may play a role as well.32,33
This study has several limitations. First, selection of participants in a clinic-based setting may have positively selected for women with genital symptoms, but also negative selection could play a role when women feel discouraged to participate for fear of stigma when reporting complaints. We used maximum efforts to reduce this type of bias by providing appropriate information and counseling in a private and unthreatening environment, and by asking staff not to book patients for the study. We estimate that more than 90% of women who came for individual counseling after group information agreed to participate in the study and believe that the study population is therefore representative of the normal PHC facility population, but not necessarily for the general population. Pregnant women, those on chronic treatment, and those with children are overrepresented at the health care facilities. This is a practical advantage because these women, and not the general community, are the ones to benefit from enhanced STI control efforts that are implemented at PHC facility level. Third, the cross-sectional study design does not allow for interpretation of causality or temporal sequence of exposure and outcome of associations observed in this study. Lastly, the degree of rurality of Mopani District should be taken into account when generalizing our data to other regions of South Africa and beyond.
This study shows a relatively high prevalence of genital and rectal chlamydia and gonorrhea in, especially young, women living in rural South Africa where the unemployment rate is high. The burden of symptomatic as well as asymptomatic infections in this population warrants the attention of health care workers, requires intensification of prevention initiatives, and informs policy design. Rectal infections are rarely considered in clinical practice, and education is required. With regard to prevention efforts, the groups to target first should be young women and those attending to the health care facility for ANC or family planning. Policy design should include special focus on these high-risk groups, but achieving control of chlamydia and gonorrhea is complicated because of high prevalence of asymptomatic, and thus untreated, infections which provide a reservoir for reinfection. In that regard, promoting condom use and strengthening partner notification and treatment systems would be important steps to reduce prevalence of infection. In addition, the development and introduction of accurate and affordable point-of-care diagnostics could be useful in specific settings. Increased efforts are warranted to control the burden of (a)symptomatic chlamydia and gonorrhea among women in rural South Africa.
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