Partner notification for Chlamydia trachomatis urogenital infections: eight years of patient referral experience in the major Portuguese sexually transmitted infections clinic,2000

Abstract

The aim of this study was to perform a retrospective evaluation of the success of patient referral for partner notification of chlamydial infections to the major Portuguese sexually transmitted infection (STI) clinic. A total of 8277 patients were screened for Chlamydia trachomatis during 2000–2007, and 695 (8.4%) tested positive. The sexual partners of 34% of these index cases attended the clinic as contacts following partner referral. In univariate analysis, heterosexual men referred partners more frequently than men who have sex with men (MSM) and HIV-negative index cases referred partners four-fold more frequently than HIV-positives; however, these associations were non-significant after multivariate analysis (adjusted odds ratio [OR] 1.4, 95% confidence interval [CI] 0.7–2.6; adjusted OR 4.2, 95% CI 0.9–18.7, respectively). Index patients who reported lower numbers of partners referred more frequently, and this association remained significant after multivariate analysis. One-third of the referred individuals tested C. trachomatis-positive; the risk for infection was three-fold higher for referred partners from symptomatic index cases (P < 0.001, adjusted OR, 95% CI 1.8–6.3). In conclusion, the results of the present study concerning sexual behaviour, HIV status and clinical signs highlight the need for further evaluations that may shape future partner notification strategies in order to reduce the chlamydial disease burden.

Keywords

bacterial disease HIV screening partner notification patient referral sexual behaviour

INTRODUCTION

Chlamydia trachomatis is responsible for urogenital infections causing cervicitis in women and urethritis in both men and women. Although C. trachomatis can cause urethral discharge and/or dysuria in men, and vaginal discharge, lower abdominal pain or postcoital bleeding in women, C. trachomatis infections are mainly asymptomatic (40% of men and 70% of women).¹ Therefore, most cases remain undetected and untreated, and can progress to serious complications, especially in women, such as pelvic inflammatory disease, tubal infertility and ectopic pregnancy.² Furthermore, individuals with C. trachomatis infection are at an increased risk of acquiring or transmitting HIV.³

Since the end of the 1990s, there has been a rise in C. trachomatis infection among western European countries.^4,5 In Portugal, there is no system for reporting C. trachomatis-positive cases to public health authorities and, consequently, its epidemiology is unknown.

The major Portuguese sexually transmitted infection (STI) clinic, the Lapa Health Centre, is located in Lisbon, Portugal, and is the only one operating on a primary care level. It is a free, open-access confidential clinic where anyone who seeks health care related to STIs can attend without payment, even those with no health insurance. Diagnostic tests for STIs and HIV, counselling, and health education are provided. Treatment is free of charge and condoms are available. Routinely, partner notification in the form of patient referral is carried out by C. trachomatis infected individuals, who are advised to refer all sexual partners from the preceding 3–6 months. This is a well-known procedure for targeting those who have undiagnosed infection and preventing re-infection of the index patient.^6–8 Indeed, early diagnosis and treatment of all infected individuals and their sexual partners are believed to reduce C. trachomatis dissemination and to prevent sequelae.⁹

In this study, we aimed to evaluate retrospectively the efficacy of patient referral from C. trachomatis infected attendees of the major Portuguese STI clinic over an eight-year period (January 2000–December 2007). Additionally, C. trachomatis prevalence, co-infection with other STIs, together with demographic and behavioural factors were also determined and evaluated.

METHODS

Study population

In the Lapa Health Centre, all clients attending for STI screening (with or without genital symptoms), either due to a new problem or through patient referral, are systematically screened for C. trachomatis, HIV and syphilis. Additional testing for other STIs (Neisseria gonorrhoeae, herpes simplex virus [HSV], human papilloma virus [HPV], Trichomonas vaginalis) is performed according to the patient's clinical presentation (Figure 1, available online only at: http://www.ijsa.rsmjournals.com/cgi/content/full/22/10/548/DC1). Genital warts are diagnosed through clinical observation.

From 2000 to 2007, a total of 8277 patients (4147 men [50.1%] and 4130 women [49.9%]), were tested for C. trachomatis, yielding 695 (8.4%) positive results (see Figure 1). Demographic data (age, gender and country of origin), behavioural information (sexual orientation, number of sexual partners in the previous six months, commercial sex work and intravenous drug use), clinical data (past HIV serology, symptoms and clinical signs and concomitant HIV/STIs) and efficacy of patient referral by C. trachomatis infected patients (index) were retrospectively evaluated in the present study.

For clarification purposes throughout the text, we define ‘index’ as the C. trachomatis-positive individuals for whom at least one referred sexual partner attended the clinic, which is designated as the ‘referred’ patient.

Laboratory diagnosis

The laboratory diagnosis of C. trachomatis, N. gonorrhoeae, T. pallidum, HSV and HIV infection was performed in the Portuguese National Institute of Health. Urine samples, and cervical and/or rectal swabs collected in 2-sucrose-phosphate (2SP) transport media were analysed for the presence of C. trachomatis DNA by the COBAS^® AMPLICOR polymerase chain reaction (PCR)-based assay (Roche Molecular Systems, Branchburg, NJ, USA) according to the manufacturer's instructions for urine or 2SP samples, as previously described.¹⁰ C. trachomatis-positive samples were further characterized, in order to determine each ompA genotype.¹¹

Cervical, urethral or rectal swabs were collected for N. gonorrhoeae isolation by culture or DNA detection by COBAS^® AMPLICOR (Roche). Syphilis diagnosis was established by Venereal Disease Research Laboratory and T. pallidum particle agglutination assay serology and/or T. pallidum detection in blood or lesion exudates by a previously described real-time PCR method.¹² The detection of HIV infection was performed on serum samples by enzyme immunoassay further confirmed by Western blot. The clinical diagnosis of genital herpes was confirmed by the detection of HSV1 and HSV2 from genital lesions both by culture in a shell vial with monoclonal antibody identification and by a real-time PCR technique (Argene Biosoft, Verniolle, France). The detection of HPV was performed by the Clart HPV2 test (Genomica SAU, Madrid, Spain) in anogenital exudates or wart-scraped cells.

Statistical analysis

The association between categorical variables was evaluated by Fisher's exact test when both variables had two categories, or by the Pearson chi-square if one of the variables had more than two categories. Logistic regression models were applied to estimate the odds ratio (OR) adjusted for other variables. The hypothesis of non-association was rejected if the P value for Fisher's exact test or chi-square test was less than 0.05. All statistical results were obtained with the package of statistical programs SPSS 15.0 (SPSS Inc, Chicago, IL, USA).

RESULTS

Overall, 695/8277 individuals (8.4%) were C. trachomatis-positive; 9.1% (379/4147) of men and 7.7% (316/4130) of women. The annual percentage of C. trachomatis infected individuals ranged from 7.0% in 2006 to 13.0% in 2001 (for men) and from 6.3% in 2004 to 9.8% in 2007 (for women). Considering the distribution of gender by age group (data not shown), infected women were younger (mean age 27 years) than men (mean age 30 years) (P < 0.001). Other demographic and behavioural data are presented in Table 1.

Table 1

Characterization of the Chlamydia trachomatis-positive individuals


	Male n = 379 (54.5%)	Female n = 316 (45.5%)	Total cases n = 695
Mean age (range)	30 (15–76)	27 (16–60)	29 (15–76)
	No. (%)	No. (%)	No. (%)
Country of birth
Portugal	224 (59.1)	195 (61.7)	419 (60.3)
PALOP	85 (22.4)	64 (20.3)	149 (21.4)
Brazil	36 (9.5)	34 (10.8)	70 (10.1)
Others	34 (9.0)	23 (7.3)	57 (8.2)
No. of sexual partners (<6 months)
0	4 (1.1)	3 (0.9)	7 (1)
1	122 (32.2)	197 (62.3)	319 (45.9)
2–4	205 (54.1)	74 (23.4)	279 (40.1)
>5	46 (12.1)	41 (13.0)	87 (12.5)
Unknown	2 (0.5)	1 (0.3)	3 (0.4)
Behavioural data
MSM	73 (19.3)
Heterosexual	306 (80.7)	315*	621 (89.4)
Sex workers	0	37 (11.7)	37 (5.3)
IDU	0	16 (5.1)	16 (2.3)
Signs/symptoms
Urethral/vaginal discharge	163 (43.0)	73 (23.1)	236 (34.0)
Dysuria, itch/cervicitis	20 (5.3)	83 (26.3)	103 (18.7)
No symptoms	196 (51.7)	160 (51.0)	356 (51.2)
HIV + previously	14 (3.7)	11 (3.5)	25 (3.6)
Co-infections	100 (26.4)	99 (31.3)	199 (28.6)
Genital warts	25 (6.6)	44 (13.9)	69 (9.9)
Neisseria gonorrhoeae	36 (9.5)	12 (3.8)	48 (6.9)
Genital herpes	13 (3.4)	13 (4.1)	26 (3.7)
Syphilis	15 (4.0)	10 (3.2)	25 (3.6)
HIV infection	11 (2.9)	5 (1.6)	16 (2.3)
Trichomonas vaginalis	^†	19 (6.0)	19 (–)
Others^‡	6 (1.6)	6 (1.9)	12 (1.7)

PALOP = Portuguese-speaking African countries (Angola, Cape Verde, Guinea Bissau, Mozambique and São Tomé and Príncipe); MSM = men who have sex with men; IDU = injecting drug user

*One woman was bisexual

^†Not screened in men

^‡ Molluscum contagiosum, scabies, pubic lice

About half of the C. trachomatis infected population, regardless of gender, presented no symptoms or clinical signs of STIs (Table 1).

Fifteen C. trachomatis ompA genotypes were detected, where E, G and F were predominant (44.3%, 12.4% and 11.8%, respectively). No association could be established between C. trachomatis ompA genotype and gender, clinical signs, co-infection, number of sexual partners, HIV status or sexual orientation. The ompA genotype determined for both index and referred patients were not concordant for five couples. Considering that the index from four out of these five couples had more than one partner during the last six months this discrepancy could be expected. As previously reported,¹³ these data suggest that the ompA genotyping method is not a reliable epidemiological marker.

Two hundred and fifteen concomitant STIs were diagnosed in 199 out of 695 individuals, where genital warts was the most frequent, being detected in 9.9% of C. trachomatis infected individuals (Table 1).

The group of C. trachomatis-infected individuals (see Figure 1) comprised 624 patients (269 women, 283 heterosexual men and 72 men who have sex with men [MSM]) and 71 referred sexual partners of C. trachomatis-positive patients. Overall, 213 sexual partners attended the clinic, referred by 209 (33.5%) index patients. All index patients referred a single partner to the clinic, except for one woman who referred two male partners and three men who referred two female partners each. All these partners attended to the clinic within a one-month period of referral. C. trachomatis positivity among referred patients was 46.1% and 21.6% for women and men, respectively.

Index patients who reported lower numbers of partners referred more frequently, and this association remained significant in multivariate analyses (e.g. 0–1 partner versus ≥5 partners, adjusted OR [aOR] 4.2, 95% confidence interval [CI] 2.1–8.2).

The analysis of patient referral by index patients (Table 2, available online only at: http://www.ijsa.rsmjournals.com/cgi/content/full/22/10/548/DC1) shows a statistically significant positive association with decreasing numbers of sexual partners in the previous six months, and this association remained significant in multivariate analyses. Also, the referral rates of HIV-negative indexes were about four-fold higher than that observed for HIV-positives, and heterosexual patients referred 1.4-fold more frequently than MSM; however, these associations were non-significant in multivariate analysis (aOR 4.2, 95% CI 0.9–18.7; aOR 1.4, 95% CI 0.7–2.6, respectively) (see Table 2).

The risk for C. trachomatis infection (Table 3, available online only at: http://www.ijsa.rsmjournals.com/cgi/content/full/22/10/548/DC1) was nearly twice as high (aOR 1.93, 95% CI 1.0–3.6) among referred patients from index men than from index women; 3-fold higher (aOR, 95% CI 1.8–6.3) among referred patients from index individuals presenting complaints or symptoms suggestive of STI and two-fold higher (aOR, 95% CI 1.0–4.1) among referred patients when the index had no concomitant HIV/STI.

DISCUSSION

Challenges for C. trachomatis prevention include screening of sexually active women below 30 years, improving partner notification practices, reducing re-infection (improved partner management and rescreening), male screening (selected high-prevalence venues) and promoting behaviours to reduce risk (delay in initiation of sex, limiting partner number, condom use, etc.).

The development of reliable nucleic acid amplification methods for non-invasive biological samples (such as urine) lowered the barrier for screening, especially in asymptomatic men.⁴ In fact, in the Lapa Health Centre, initially all women were screened but only symptomatic men were tested on their first attendance. Interestingly, the inclusion of asymptomatic men during the study period did not alter the C. trachomatis positivity in this gender. In addition, about half of the studied women presented no symptoms or clinical signs of STI (Table 1). This highlights the importance of screening, as asymptomatic carriers constitute a reservoir of infection and are likely the basis for the high prevalence of C. trachomatis infections.

Although prevalence data from the general population are not available in Portugal due to the absence of a system for reporting C. trachomatis-positive cases, previously published data showed 4.6% (51/1108) prevalence, which was lower than that observed in the present evaluation (8.4%).¹⁴ However, while our study has been carried out in a potentially high-risk population (STI clinic attendees), the other was a cross-sectional study involving sexually active women aged under 30 years attending general practice, family planning and teenage clinics in Lisbon.

In the present study, most C. trachomatis-positive cases were observed in young people, but the mean age (29 years) was higher than described in most published data.^1,4 However, for women, the higher rate of infection was observed in the 20–24 age group, which is in agreement with other studies.¹ In men, this observation is also in agreement with other studies, although the age group with the highest rate of infection was higher (25–29 years) (chi-square test: P < 0.001).¹⁵

About 34% of the infected patients referred their sexual partners to the clinic, consistent with other studies. In fact, the efficacy of partner notification for STIs has been established from 13%¹⁶ to 82%¹⁷, varying with dissimilar health-care systems between countries and according to different criteria for the evaluation of partner referral success. However, we observed that the referral rate of heterosexual men was higher than the obtained from MSM (although non-significant in multivariate analysis; see Table 2).This observation is probably explained by sexual behaviour, especially the frequency of partner change.¹⁸ This is supported by a previous study¹⁹ of syphilis among MSM, where the majority of the MSM reported anonymous partners. Moreover, in our study, the number of sexual partners in the last six months seems to be a crucial factor for patient referral as there was a statistically significant positive association with lower number of sexual partners in the previous six months. This is consistent with a previous report, where index patients with two or more partners were less likely to refer their sexual contacts.¹⁸ We also observed that the referral rate was influenced by the HIV status of the index; HIV-negative patients referred four times more frequently than HIV-positive index cases (although non-significant in multivariate analysis), which may be due to difficulties HIV-positive patients have to inform their partners about a new STI diagnosis. To our knowledge there are no other reports in Europe about the efficacy of partner notification including HIV status that could support our findings.

Curiously, only one-third of the referred individuals tested positive for C. trachomatis. Although the precise reason for these findings cannot be determined, several factors may contribute for this discrepancy, namely, the status of infection at the time of sample collection, the first to become infected (index or referred) or the route of transmission. Supporting this, we have previously assessed the correlation between chlamydial load and disease pathogenesis¹³ and we found profound load differences between couples, which led us to the above-cited possibilities. Referred patients from index men were at double the risk for acquiring a chlamydial infection when compared with referred patients from index women. A possible explanation for this finding would be the longer duration of infectiousness in women.²⁰

We also found that risk for C. trachomatis infection was three-fold higher for referred patients from index individuals presenting with complaints or symptoms suggestive of STI. This would be expected if the presence of symptoms or clinical signs resulted from a higher chlamydial load that would increase the probability of transmitting the pathogen. However, in a previous study involving about 200 C. trachomatis-infected patients¹³ we observed that the chlamydial load was similar among symptomatic and asymptomatic individuals, which suggest that chlamydial transmission is not influenced by the bacterial load.

One misleading result was the two-fold higher risk for C. trachomatis infection observed among referred patients when the index had no concomitant HIV/STI. We find it quite surprising as it is assumed that having one STI may facilitate the acquisition of another STI. However, this general assumption may depend on physiological and/or microbiological modifications that are STI-specific (such as epithelial alterations, pH changes, commensal microbial fluctuations) rather than on the status ‘having any other STI’.

In conclusion, our results provide evidence that patient referral is a powerful tool for detecting asymptomatic carriers, and consequently for lowering the prevalence of C. trachomatis infection. Although in the present study this assessment was particularly effective for index individuals presenting clinical signs, further studies are needed to support this evidence. Also, considering the lack of efficacy of patient referral among HIV-positive index cases, it seems crucial to develop accurate strategies to improve their partner notification in order to prevent dissemination of HIV.

Footnotes

ACKNOWLEDGEMENTS

We thank Maria Arminda Ferreira for performing chlamydial laboratory diagnosis.

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Partner notification for Chlamydia trachomatis urogenital infections: eight years of patient referral experience in the major Portuguese sexually transmitted infections clinic,2000–07