Chlamydia prevalence in the general population: is there a sex difference? a systematic review

Search strategy

We performed a search of the literature in the electronic bibliographic databases PubMed, Embase and CINAHL for English-language articles published between January 1, 2000 and December 31, 2012. The following search terms were used: “Chlamydia trachomatis” AND “prevalence” AND “population-based study OR population”. Reference lists of included articles were checked for potential studies. Also, the reference lists of selected systematic reviews were hand-searched for further publications of interest [16, 24, 25]. A flow chart of the search is shown in Figure 1.

Inclusion and exclusion criteria

Studies were eligible for inclusion in the review if they (1) unambiguously reported prevalence of Chlamydia trachomatis infection in the general population, (2) compared and reported the chlamydia prevalence among men and women, (3) reported data from a population that was described as non-medical or non-health-care setting, (4) used nucleic acid amplification tests (NAAT) for diagnostic testing and (5) used a cross-sectional study design. We excluded articles that (1) reported only on men or women, (2) reported on selective populations, for example commercial sex workers, soldiers, ethnic groups, gynaecological patients or follow-up, (3) reported on prevalence among individuals with urogenital symptoms and (4) used serology for diagnosis. The first author (PD) applied the inclusion criteria to potentially eligible studies.

Methodological assessment of reviewed studies

The studies were assessed and information extracted by two authors independently (PD, DT). Disagreements were resolved by discussion and consensus with the third author (TLJ). To assess the usefulness of the prevalence studies four questions were required to be answered affirmatively [26, 27]: (1) is the problem being studied in the general population with data obtained from registers or data administrations independently from a health care setting?; (2) Is the study’s sampling design fully described?; (3) Was a probabilistic sample used?; (4) Is prevalence broken down by sex? Further assessment of the quality of the studies included the response rate of the total sample and sex subgroups (major flaw if < 40%), reporting number screened, reporting of prevalence type and total prevalence, prevalence in subgroups and precision of estimation (95% CI, error) [26]. If necessary, authors were contacted by email for additional information for example the origin of the registries or administration database [28, 29].

The prevalence for both men and women, and if available the highest prevalence rate by age and sex, were extracted. We calculated the difference in prevalence between the sexes for each study and its 95% confidence intervals [30]. The data were not pooled for meta-analysis. It was likely that there would be considerable heterogeneity between studies making any formal meta-analysis less valid. Also, it was not considered important to the interpretation of the data because of the different geographical location of each study and therefore of limited clinical added value of this pooled prevalence rate to GPs.

Description of included studies

The majority of the included studies were conducted in the general community (18), three were conducted in general practice [19, 31, 40] and four in schools [35, 42, 46, 51]. We included the studies that recruited participants from general practices in the Netherlands and the UK because in these countries the vast majority of its population is registered at one general practice [53]. We included studies from Europe (13) [19, 28, 29, 31, 32, 38–40, 44, 47],[49, 51, 52], the United States of America (6) [34, 35, 41, 42, 45, 50], Asia [36, 46, 48], Africa [33], Australia [37] and the Caribbean [43].

Study sample sizes were moderate. The number of individuals tested in each study varied considerably, ranging between 123 and 7555 participants. In all studies but two the number of female participants was higher than male participants [28, 33]. Most studies reported 95% confidence intervals for their prevalence rates of chlamydia infection in men and women but only ten studies conducted adequately statistically comparison of prevalence rate by sex [28, 33, 35, 36, 38, 39, 43, 45],[49, 50]. Also, the age groups chosen varied considerably, including individuals at puberty or adolescence to adulthood (minimum 12 years and maximum 67 years). The response rates varied in men from 11.9% to 79.0% and in women from 18.9% to 86.0%. Where reported, response rate in all studies was higher for women than for men. Only eleven studies reported total response (31.5% to 88.6%) [32–35, 39, 41, 42, 46, 48, 50, 51]. In three studies the total response rate or response rate for men and women separately was below 40% (major flaw) [19, 40, 49]. In four studies the response rate for men was below 40% only [31, 38, 44, 52]. Of the seven studies reporting low participation rates, six studies invited participants by mail [19, 31, 38, 40, 44, 49, 52].

The most commonly utilized sample was urine or first voided urine for both men and women. First voided urine samples were tested for all of the male population. For women, in five studies a self-obtained lower vaginal swab was used or offered [19, 29, 40, 44, 47]. The prevalence of symptoms was reported in only eight studies [19, 33, 35, 38, 42–44, 52].

Prevalence of chlamydia infection by sex

In urban settings, chlamydia prevalence for women ranged from 2.8-6.2% and for men from 1.6-5.3% (Table 2). In rural settings, chlamydia prevalence for women ranged from 1.6-7.3% and for men from 1.0-3.9%. Prevalence rate for women was highest in a study with participants aged 15–20 years. Ten studies reported on chlamydia prevalence estimates from studies conducted in rural and urban settings. Chlamydia prevalence for women ranged from 1.1-6.9% and for men from 1.2-7.3%. Highest prevalence rates in women and men were in studies with predominantly adolescents and small sample sizes.

The five studies that used self-obtained vaginal swabs in women and first voided urine in men, found no statistically significant difference in chlamydia prevalence in men and women (Table 2) [19, 37, 40, 44, 47]. Reported prevalence estimates were 1.6–6.9% for women and 1.4–5.3% for men. In sixteen studies first voided urine was used in both women and men as test specimen. In these studies, chlamydia prevalence in women ranged from 1.1-10.6% and in men from 0.1-12.1%.

Prevalence of chlamydia infection by sex and age group

Overall, in both men and women young age groups (<25 years) have higher chlamydia prevalence rates than older age groups but chlamydia prevalence in young age groups is not different for men and women. In six studies the highest prevalence of chlamydia infection was in the same age group for men and women [29, 31, 40, 45, 51, 52]. In five studies women compared to men had the highest chlamydia prevalence at a younger age group [32, 36, 38, 41, 47].

Furthermore, in all fourteen studies but two, the highest chlamydia prevalence occurred among participants < 25 years of age; in women ranging from 2.1-6.6% and in men from 1.0-6.3%. In two studies the highest age group was > 25 years in both men and women. One study, originated from India, reported the highest chlamydia prevalence in men 31–45 years of age and in women 31–35 years of age (2.1% versus 1.9%). In a study from China, the highest chlamydia prevalence was found in men aged 25–34 years and in women aged 35–44 years (3.9% versus 4.2%) [36, 48].

The presence of symptoms by sex

There were eight studies that reported information on the presence of symptoms among individuals tested [19, 33, 35, 38, 42–44, 52]. The absence of symptoms in urogenital chlamydia infections varied in men from 73.9% to 94.6% and in women from 45.3% to 95.5%. In all studies but one [35], the absence of symptoms was higher in men than in women.

Statement of the principal findings

In our systematic review of 25 studies, we found modest sex differences in the prevalence of chlamydia infection between men and women in the general population. The prevalence for women varied from 1.1% to 10.6% and for men from 0.1% to 12.1%. Nine out of twenty-five studies showed a statistically significant higher prevalence of chlamydia among women compared to men. The majority of the included studies did not found a sex difference. Where studies reported age-based estimates, younger participants had higher prevalence than older participants but this is the case for both men and women. Also, the prevalence of Chlamydia trachomatis in urban and rural areas did not differ between men and women. The review highlighted that chlamydia prevalence was highly variable between countries but with rates often as high in men as in women. The commonly held assumption that chlamydia infection is more prevalent in women than in men should therefore be reconsidered.

Strengths and weaknesses of the study

Two methodological issues need to be addressed as they may influenced the validity of these findings. Firstly, the majority of the studies had low or unspecified participation rates more for men than for women (< 60%). A low participation rate can induce non-participation bias and the population sample under study may not be generalizable to the whole population [54]. Few studies collected data on non-respondents for comparison with respondernts to assess the implications of study nonparticipation. It is uncertain how and if non-participation bias influenced the results. Secondly, most studies used first voided urine in women instead of vulvovaginal swabs. Both specimens from women are suitable but the vulvovaginal swab is the specimen of choice in women [55]. The number of infections identified in women in the studies using first voided urine may have been higher when using a vulvovaginal swab. The sensitivity of first voided urine for the detection of chlamydia infection in women is lower than vaginal specimens. Last we did not address specific ethnic backgrounds in our review. Few studies presented chlamydia infection by ethnical background. Ethnicity is a known risk factor for STIs [34, 35].

The strengths of this review are that, in our opinion, it provides the most comprehensive review to date of chlamydia prevalence estimates in the general population directly comparing men and women. We conducted comprehensive literature searches of multiple databases and used rigorous methods to appraise the articles. It is unlikely that we excluded important articles in this field. All studies used the nucleic acid amplification test with high sensitivity and specificity not only greatly enhancing the acceptability of a screening intervention but also increasing the reliability of the prevalence estimates. It is the first review in this area to confirm the previous conclusions in other systematic reviews of chlamydia prevalence estimates in non-population-based studies that the prevalence of urogenital chlamydia infections is as high in men as in women [16, 24, 25].

Implications

It is clear from this review that men are also an important reservoir of chlamydia infection for women and as such men should also be targeted for chlamydial screening. The vulnerability of women for a urogenital chlamydia infection in different countries did not emerge as a robust trend in this review of the literature. The reason for the reported sex differences are explained in the literature as artefacts or bias of reporting and the fact that women are more studied and more tested than men [16, 24, 25]. Chlamydia screening is frequently performed in women even in the absence of symptoms for example in routine gynaecologic care, Pap test, IUD insertion or unintended pregnancy, and it is more common to perform population-based chlamydia screening activities for women [13, 14]. By contrast, fewer men are diagnosed in primary care: men are often treated for chlamydia without a definitive diagnosis, based upon symptoms such as urethritis or being a contact of a women with a chlamydia infection [56, 57]. Also this review shows that men consistently have lower participation rates in chlamydia prevalence studies. The results of this study confirm and strongly support the need for higher coverage of men in chlamydia screening and research activities [4, 24].

The conclusion from this review is that the prevalence of chlamydia infection in men and women in the general population is more similar rather than dissimilar regardless of age or level of urbanisation. According to the literature, many factors shape women’s and men’s risks for chlamydia infection differently [22, 23, 58]. Biological predisposition and certain gender-specific behaviours are mentioned in the literature as possible reasons for women being more at risk for chlamydia and other STIs than men [58, 59]. For example, cervical ectopy, especially in young women, may increase their susceptibility to chlamydia infection. Cervical ectopy is more common in women using oral contraceptives [60]. Hormonal contraceptives are associated with an increased risk of chlamydia infection [60–62]. Vaginal douching is associated with bacterial vaginosis and HIV, both increasing the risk for other STIs [63]. A direct association between douching and chlamydia is less consistent [64]. In the male however, little is known about analogous phsysiological changes that might affect a man’s risk of infection with chlamydia. Circumcision in men, not in women, appears to reduce the risk of acquiring STI [65]. Men tend disproportionately to place monogamous women at risk for STI [58]. All this may be true, in the general population it seems to result in a modest difference in the prevalence of chlamydia among men and women only.