Systematic literature review and meta-analysis of urinary tract infections and sexually transmitted infections in symptomatic women: prevalence, patterns and clinical implications

Introduction

The symptoms of urinary tract infections (UTIs) and sexually transmitted infections (STIs) often overlap and represent a common reason for accessing healthcare throughout the world. The WHO approximate that nearly 1 million people become infected every day with curable STIs.1 The Centers for Disease Control and Prevention (CDC) estimate that the incidence of STIs occurs at a rate of approximately 20 million per year in the USA alone, with many unreported cases, while UTIs trigger 2–3 million emergency department (ED) visits annually.2 Sexually active women are at higher risk of developing STIs and, when unmanaged, can lead to high morbidity, especially in women of reproductive age.2

In the emergency department, it is common for UTIs to be treated empirically without obtaining urine cultures, a practice not limited to the USA. Even if cultures are collected, the results require more processing time compared with urinalyses. However, urinalysis in the context of both UTIs and STIs can reveal sterile pyuria and detectable leucocyte esterase, so this approach may be prone to misdiagnoses. This is particularly relevant for women presenting with non-specific genitourinary symptoms, such as dysuria, frequency and urgency.3 Establishing the correct diagnosis can be harder in low-income to middle-income countries where access to diagnostic tests for sexually transmitted pathogens is limited.1

The CDC has warned that nearly 50% of all antibiotics prescribed in emergency departments for UTIs and STIs in the USA are unnecessary or inappropriate.4 Treating patients with sterile pyuria for UTIs can lead to increased antibiotic resistance, Clostridioides difficile-associated infections and medication-associated adverse effects.3 Furthermore, missed and, therefore, untreated STIs can lead to complications such as infertility, ectopic pregnancy, pelvic inflammatory disease and spread of infection to sexual partners.5

Given the overlap between UTI and STI symptoms, identifying clinical predictors for pelvic infections in women with these conditions is crucial for improving diagnostic accuracy and reducing the risk of complications.1 2 This study aims to systematically review and analyse the prevalence of the most common STI pathogens among symptomatic women, assess the proportion of women with STIs who also have positive urine cultures and discuss the clinical implications of UTI overdiagnosis and STIs underdiagnosis in adolescent females (aged>13 years) and women.

Search strategy

We performed literature searches in PubMed, CINAHL, Scopus, Web of Science, Embase and Cochrane up to 3 June 2024. Our search strategy is described in online supplemental appendix 1 and the PubMed search strategy was adapted for the other databases. We found 7719 studies in the above databases, of which 2219 were duplicates. After screening the 5500 remaining studies, 5433 studies with overlapping patients, incomplete data or that did not meet the patient, intervention, comparison and outcome (PICO) inclusion criteria were excluded using Rayyan app through consensus.8

Inclusion criteria for this systematic literature review were as follows: scientific journals; original research manuscripts; peer-reviewed; evaluating STIs and UTIs in females >13 years of age, where women presented with genitourinary tract complaints and had an abnormal urinalysis. An abnormal urinalysis was defined as the presence of pyuria (≥5–10 white blood cells per high-power field), positive leucocyte esterase or nitrite positivity. Studies were considered for inclusion regardless of whether or not they included pregnant women. Studies without simultaneous diagnostic work-up for UTI and STI, studies including men, children under 13 years of age, asymptomatic patients, studies with no specification of UTI diagnostic criteria (ie, whether it was clinical or guided by urine culture/urinalysis) and studies that did not use diagnostic STI tests were excluded. After applying the exclusion criteria, 11 studies were included in the systematic literature review and nine studies provided quantitative data that allowed for inclusion in the meta-analysis (figure 1 and table 1).

Figure 1

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Literature search for articles of the sexually transmitted infections (STIs) and urinary tract infections in women.

Table 1

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Summary of characteristics of studies included in the systematic literature review

This study applies a PICO9 framework in a primarily descriptive manner, focusing on females aged >13 years with genitourinary complaints and abnormal urinalysis (P), under a simultaneous diagnostic approach for UTIs and STIs (I), without predefined comparators (C). The outcomes (O) included prevalence of cervicovaginal STIs and UTIs, identification of pathogens and associated symptoms. We also explored potential clinical predictors of pelvic infection that might inform diagnostic decision-making.

Results pooled by symptoms, prevalence of STIs and confirmed STI with positive urine culture

The most commonly reported symptoms are described in figure 2 (online supplemental table 3 and table 4) and were suprapubic pain (59%), dysuria (54%), urinary frequency (48%), urgency (47%) and vaginal discharge (26%).5 12–14 17–20

Figure 2

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Venn diagram of overlapping symptoms between urinary tract infections and sexually transmitted infections

The prevalence of STIs of 23.5% is described in online supplemental table 1 and it ranged from 9% to 53% (figure 3), with Trichomonas vaginalis (18.8%), Chlamydia trachomatis (13.3%) and Neisseria gonorrhoeae (4.5%) being the most frequently detected pathogens as well the prevalence of each STI pathogen per each study (online supplemental figure 1). Coinfections of multiple STI pathogens were rare in the included studies, occurring in 0.9%–2% of cases, described as Neisseria gonorrhoeae plus Chlamydia trachomatis, Chlamydia trachomatis plus Trichomonas vaginalis and Neisseria gonorrhoeae plus Chlamydia trachomatis coinfections.18 20

Figure 3

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Forest plot of the meta-analysis of the prevalence rate of symptomatic women with sexually transmitted infections (STIs).

Accuracy of clinician’s diagnosis for UTIs ranged from 34% to 95% (mean 56.9%), while for STIs it ranged from 26% to 75% (mean 47%) (online supplemental figure 2 and table 4). Among women with confirmed STIs who also had a positive urine culture, the prevalence rate was 4.7% and it ranged from 4% to 9% (online supplemental table 2 and figure 4). Complications from underdiagnosed UTIs and overdiagnosed STIs were only mentioned in six studies but none addressed the rates of the respective complications.12 15 18–20 None of the studies reviewed addressed bacterial resistance rates.

Figure 4

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Forest plot of the meta-analysis of the prevalence rate of symptomatic women with sexually transmitted infections (STIs) and positive uroculture results.

Regarding quality assessment scores, no studies were considered high quality (≥24 of the 28 possible points) per the Down and Black quality tool, six studies were considered good quality (19–23 points),11 14 15 18–20 and five were considered fair (14–18 points).5 12 13 15 16 The details of Downs and Black score for each study are described in online supplemental table 5.

Discussion

This systematic literature review and meta-analysis aimed to explore the prevalence, patterns and clinical implications of UTIs and STIs in women presenting with genitourinary symptoms. Diagnosing these conditions in symptomatic women poses significant challenges due to overlapping clinical presentations. Our findings revealed that the prevalence of STIs in women with non-specific genitourinary symptoms can be as high as 53% with 9% presenting simultaneously with a positive urine culture for a different pathogen. The accuracy of clinician’s diagnosis regarding UTIs and STIs was, respectively, 56% and 47% with nearly half of the cases misdiagnosed (online supplemental table 4). This highlights the difficult of relying solely on clinical presentation for diagnosis. It is also essential to consider hypoestrogenism in older women, as it can further complicate the diagnostic process.19

While the US Preventive Service Task Force recommends screening for Chlamydia trachomatis and Neisseria gonorrhoeae in all sexually active women ≤24 years or those who are at increased risk for infection (grade B recommendation), there is no consensus on screening for Trichomonas vaginalis.22 However, testing women with genitourinary symptoms for sexually transmitted diseases is not a common practice. Additionally, high-quality diagnostic tests, such as point-of-care (POC) testing for STI screening, are not widely accessible, particularly for Trichomonas vaginalis with many physicians relying on less sensitive methods like vaginal wet mounts.23 This contributes to missed diagnoses, particularly since Trichomonas vaginalis was identified as the most prevalent non-viral STI pathogen in our meta-analysis (18.8%), followed by Chlamydia trachomatis (13.3%) and Neisseria gonorrhoeae (4.5%). According to Tomas et al, Trichomonas vaginalis is implicated in 45% of missed STI diagnoses (ie, women who were mistakenly diagnosed with UTI and later tested positive for STI), identified mainly when tested by non-NAAT methods.14 Additionally, several studies have postulated that Trichomonas vaginalis infection can become a pathway for other pathogens into the genitourinary tract, making women more susceptible to other infections.12 19 23 Therefore, the CDC recommends that all women seeking care for symptoms of vaginal discharge should be tested for Trichomonas vaginalis infection.24–26 Although not evaluated in this meta-analysis, herpes virus may be a contributor to prevalence rates, with recent studies showing 0.2% of prevalence in USA alone.27

Four studies in our meta-analysis highlighted that certain symptoms were predictors of a subsequent pelvic examination, including complaints of vaginal discharge, obtaining a sexual history, abdominal or pelvic pain and urinary frequency. Interestingly, urinary frequency was found to be associated with a reduced likelihood of a pelvic examination being performed.5 13 18 20 These findings suggest that clinicians may not prioritise pelvic examinations in women presenting with urinary frequency, potentially overlooking the diagnosis of pelvic infections. In addition to these predictors, other factors must be considered when diagnosing female patients with documented STIs. Shipman et al reported that the rate of sterile pyuria can reach 28% and nitrite-positive urinalysis was 18% more likely to be associated with negative urine cultures.12 Advani et al recently discussed the poor positive predictive value of urinalysis parameters for diagnosing a UTI, emphasising that no isolated parameter had good sensitivity (≥95%) for UTI. When examining urinalysis parameters for their negative predictive value (NPV), absence of trace leucocyte esterase and pyuria (≥5 white blood cell/high power field) had a high NPV (≥95%) for UTI.28 So, relying solely on symptoms that mimic UTIs, pyuria or positive nitrite to presume a UTI is present can lead to undiagnosed cases of STI. This in turn may lead to a variety of complications, such as pelvic inflammatory disease (that causes 75 000 to 225 000 cases of infertility annually in the USA), besides morbidity and mortality related to ectopic pregnancy, adhesions and chronic pelvic pain.12 15 18–20

Other studies in this systematic review showed that when combining routine care and study-driven urine cultures, around 50% of the subjects empirically diagnosed with a UTI in the emergency department had a positive urine culture, which shows us the other side of the problem: the overdiagnosis of UTI.12 14 Shipman et al discovered that 66% of prescribed antibiotics for UTI in ED were unnecessary in women with confirmed STIs, that is, for women with a negative culture and positive test for STI.12 Although there may be cost savings from not performing urine culture, unnecessary antibiotic administration in those managed exclusively based on the clinical presentation is a public health problem as community-associated E. coli infections have become increasingly drug resistant.6 The UTI diagnostic error, that is, not diagnosing a UTI when present, can worsen infectious conditions, leading to pyelonephritis and even sepsis due to UTI.20

In the context of STIs, earlier trials indicated that due to resistance, treatment failure occurs in more than 5% of patients when using azithromycin or doxycycline for Chlamydia trachomatis infection.29 Other studies highlighted that there is a high prevalence of Neisseria gonorrhoeae with resistance to fluoroquinolones, macrolides and cephalosporins, leading to increasingly expensive and less available antibiotic treatments.30 Hence, the present-day public health crisis of antimicrobial-resistant pathogens will increase medical costs of severe complications that compromise the general and reproductive health of infected women.30 Therefore, there is an urgency to improve the diagnostic accuracy in these women to initiate more effective treatments early on in order to reduce associated morbidity and mortality.

Notwithstanding these complications, women with genitourinary symptoms continue to be neglected. This systematic literature review and meta-analysis analysed the diagnostic accuracy and, on average, 50% of STI and UTI cases may be misclassified, which can distort prevalence rates. In turn, information on prevalence of STIs can influence public policies such as advertisements about risky sexual behaviours and screening protocols. Another aspect of the problem is that a large proportion of women with STIs may be asymptomatic, although data to quantify this proportion are still limited.

Challenges and gaps remain in the implementation of public policies on STIs, especially in low and middle-income countries.1 In this context, there is an urgent need to strengthen the role of primary healthcare and expand access to STI testing and treatment, including the most vulnerable populations and notifying sexual partners. In addition to tracking asymptomatic patients and monitoring primary prevention, we also need to improve the approach to sexual health in women with genitourinary symptoms, including adolescent women, as they are one of the most vulnerable populations with several questions about how to protect themselves and about health education.

To improve diagnostic accuracy in symptomatic adolescent and adult women, we suggest training healthcare professionals to correlate clinical data with positive urine culture when diagnosing a UTI in addition to search STIs in women with genitourinary symptoms. Furthermore, we recommend higher sensitivity methods for sexual infections such as POC testing, without missing the window of opportunity for diagnosis especially in women of reproductive age. POC testing offers a valuable opportunity to improve diagnostic accuracy and ensure timely, appropriate treatment. Rapid and sensitive POC diagnostic tools, such as NAATs, can help differentiate between UTIs and STIs in women presenting with overlapping genitourinary symptoms. Incorporating POC testing into ED protocols can reduce the reliance on empirical treatments that may lead to diagnostic errors, unnecessary antibiotic prescriptions and delayed treatment for STIs. For instance, rapid NAAT for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis could guide immediate decision-making and allow clinicians to initiate targeted therapies while awaiting confirmatory testing results.

The diagnosis will be even more reliable when combining sexual history, pelvic examination, urinalysis, urine culture and tests for STIs in women who seek emergency care with overlapping symptoms. Treatment can be empirical with combinations of ceftriaxone, azithromycin and doxycycline in women at high risk for STIs, varying according to institutional protocols. Follow-up of these women should involve guided antibiotic therapy and treatment of sexual partners when appropriate, or even stopping antibiotics when necessary. Further studies are needed to evaluate the cost-effectiveness of empirical therapy for STI in women with typical symptoms, considering possible adverse effects such as bacterial resistance. Furthermore, the cost-effectiveness of NAAT and other sensitive methods for STI should be evaluated in further studies.

Limitations

Despite the comprehensive nature of this review, there are several limitations to consider. Most included studies were conducted in the USA, limiting the generalisability of findings to other populations and settings. The included studies varied in design, quality, population sample size and diagnostic criteria, which may contribute to heterogeneity in the results. Geographical differences in pathogen prevalence and access to diagnostic tests further complicate the interpretation of results.

The lack of standardised screening guidelines for certain STIs, such as Trichomonas vaginalis, and the varying access to diagnostic tests across different regions and healthcare settings might have impacted the reported prevalence rates and diagnostic accuracy. Another limitation is that the studies only considered non-viral STIs and, for example, herpes simplex virus can strongly contribute to the symptoms presented and unfortunately were not evaluated.

Another important point is that comparing diagnostic strategies—such as symptom-based versus test-guided approaches—would provide stronger clinical insights into antibiotic overuse and diagnostic accuracy. However, the studies included in this review predominantly reported prevalence data without stratifying outcomes based on the diagnostic protocol employed. This limitation underscores the need for future research comparing diagnostic pathways, such as point-of-care NAATs versus empiric treatment, to better inform clinical decision-making. Furthermore, the review did not consider the impact of socioeconomic factors, cultural differences and healthcare access, which can influence the prevalence and diagnosis of UTIs and STIs.

Conclusions

The findings underscore the importance of accurate diagnosis and appropriate treatment of both UTIs and STIs to prevent unnecessary antibiotic use, reduce the risk of antibiotic resistance and avoid significant complications associated with untreated STIs, such as infertility, pelvic inflammatory disease and ectopic pregnancy. Emergency department protocols should consider these findings to improve diagnostic accuracy and patient outcomes in women with genitourinary symptoms. Potential solutions to these problems include performing a pelvic exam, asking about sexual history and routinely testing women of reproductive age for STI with highly sensitive tests such as NAAT methods. It is also important to always consider an STI diagnosis even if the symptoms are suggestive of UTI. Furthermore, it is advisable to request a urine culture to confirm UTI rather than relying entirely on symptoms or positive nitrite and pyuria. Point-of-care testing for STIs should be considered in emergency departments to address the accuracy of diagnosis.