In this issue of Sexually Transmitted Diseases, Chirenje, et al.1 describe a secondary analysis of the VOICE2 study focusing on risk factors for incident sexually transmitted infections (STI) among a cohort of women in sub-Saharan Africa. Although the primary focus of neither the study nor this analysis was on STI control, one of the important take home messages of this article is that accurate diagnosis of STI requires more than syndromic management which focuses exclusively on treatment of symptomatic women. Given the asymptomatic nature of infection with Chlamydia trachomatis, Neisseria gonorrhoeae, and even Trichomonas vaginalis, syndromic management by definition misses anywhere from 40% to 70% of infections. As a result, women without symptoms are not receiving treatment for infections that have been epidemiologically linked with pelvic inflammatory disease,3,4 tubal factor infertility,5 adverse outcomes of pregnancy,6,7 and increased risk of human immunodeficiency virus (HIV) transmission or acquisition.8,9
Assessing the true impact of STI on HIV incidence has been historically difficult. The importance of case ascertainment using highly accurate diagnostics to avoid bias was well described in the context of 3 trials conducted in the late 1990s in East Africa. The Rakai, Mwanza, and Masaka trials each assessed a community-based approach to STI reduction as a means of reducing HIV incidence.10 One of the trials (Rakai) demonstrated a substantial reduction in HIV incidence after improved access to syndromic management for STI compared with control communities, whereas the Masaka trial showed no difference between communities receiving enhanced STI prevent education and improved access to syndromic management. Finally, the Rakai trial showed no effect on HIV seroincidence after mass treatment in intervention communities versus control communities. The studies each had a different design, and the methods for assessing the population prevalence of STI varied among the trials. The impact of poorly performing diagnostics on the eventual findings of the trials has been analyzed in detail and found to be responsible for substantial bias in estimation of population STI prevalence.11
The VOICE study measured incident STI using molecular diagnosis for chlamydia/gonorrhea, a highly sensitive rapid assay for trichomonas, and quality controlled syphilis serology. Three major points of concern were highlighted in the data obtained using state-of-the-art diagnostics. First, and of critical importance, fewer than 30% of all incident infections were diagnosed in the context of a clinical visit for symptoms of disease. The remainders were diagnosed at regularly scheduled study visits suggesting that, if these women were not enrolled in a research protocol, they would not have sought care for these infections. Second, beyond age, which is not amenable to intervention, the highest STI incidence rate ratio was associated with previous infection (measured at baseline). Finally, HIV incidence was observed to be highest in those settings where STI incidence was also high.
The data generated in the VOICE study once again demonstrate that a substantial burden of disease remains in settings where syndromic management is the only available option for STI control. In this study, 20% of women were diagnosed with chlamydia, gonorrhea, trichomonas, and/or syphilis at the enrollment visit using diagnostic methods not routinely available in all settings in sub-Saharan Africa where the study was performed. This demonstrates an unacceptably high STI prevalence in these HIV-endemic settings.
What do these data tell us that we didn’t already know? Not a great deal. In fact, in upper-income countries (UIC) many of the guidelines12,13 for STI control are based on research showing that annual screening based on age, regardless of the presence or absence of symptoms, can identify a substantial proportion of cases of chlamydial infection and, further, that rescreening every 3 months among those with an identified infection is useful based on reinfection risk.14,15 However, despite these guidelines, case rates for all curable STI continue to increase globally.16,17 In UIC, this increase may be linked to a lack of full adherence with the guidelines13,18 and lack of access to sexual health services in resource constrained settings.19 In lower- and middle-income countries (LMIC), the continually high prevalence of STI in some populations is likely due to reliance on syndromic management which is equivalent to lack of access to adequate sexual health services.
So why is syndromic management still being used, particularly in LMIC as well as resource limited settings within UIC? Technology that could rapidly and accurately diagnose STI exists, but has yet to reach a point where these tests are feasible to implement in LMIC outside of research settings. Assays still require external power sources, refrigeration, and/or are prohibitively expensive. Many groups, in both academia and industry, are conducting research on assay development designed to meet the needs of LMIC, but the prioritization of this work in UIC, where the resources exist to perform this developmental work, is not high.
Ultimately, the issue is one of human rights – those populations at the highest risk for both STI and HIV are generally marginalized populations or populations with very limited political voice. It is time to redouble our efforts related to development of highly accurate point-of-care STI diagnostics that can be utilized in resource constrained settings. This will improve our ability to identify and treat curable STI's for their own sake and in order to avoid the sequelae of untreated infections. We know the lessons, we have the technology, and we need to apply what we have learned to make a substantial impact on global STI, and possibly HIV, burden in the near future.
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