The COVID-19 pandemic has highlighted the vital role of diagnostic testing in the monitoring and management of infectious diseases, and has further led to innovative efforts in academia and industry to improve testing technology and practices. There is abundant opportunity to apply lessons learned from the pandemic to other disease outbreaks, which each have their own unique diagnostic and treatment challenges to overcome. Sexually transmitted infections (STIs) represent a group of diseases for which comprehensive screening and surveillance would greatly benefit public health, but for which significant hurdles exist in terms of access to testing and, in some cases, detection sensitivity.
Factors such as the emergence of difficult-to-detect antibiotic-resistant disease strains and the social stigma attached to STI diagnoses can contribute to rising cases – in fact, preliminary data from the Centers for Disease Control and Prevention (CDC), published last month, reveals an increase in reported cases of chlamydia, gonorrhea and syphilis in 2021.1 To curb the upward trend in STI cases, testing approaches must be adapted to overcome current diagnostic challenges. Greg Stock, general manager of PerkinElmer’s EUROIMMUN Division, and Ilana Heckler, scientific affairs associate of PerkinElmer’s EUROIMMUN Division, recently discussed some of these challenges – and their potential solutions – in an interview with Labcompare.
The Perils of Antibiotic Resistance
Antibiotic resistance in STI-causing bacteria is a major problem that clinical labs must keep in mind when considering their testing approach. Neisseria gonorrhoeae, the bacteria that causes gonorrhea, is particularly notorious for evolving to evade most treatment options over the years; this frightening progression toward near “untreatable” status has prompted the CDC to label drug-resistant gonorrhea an “urgent public health issue”2 and further led the World Health Organization (WHO) to implement a “Global Action Plan to Control the Spread and Impact of Antimicrobial Resistance in N. gonorrhoeae.”3 Both the CDC and WHO emphasize the importance of surveillance and testing – including antimicrobial susceptibility testing – in combating this threat. But the emergence of new strains also complicates diagnostic testing.
“Antibiotic-resistant strains are difficult to detect. For example, Gonorrhea, in particular, has been known to develop antibiotic resistance,” said Heckler. “Laboratories need to track resistance and be prepared to adapt their technology to new strains to avoid false-negative results.”
Nucleic acid amplification tests (NAATs) such as PCR-based tests, while generally sensitive for both diagnosing and determining antibiotic resistance in STIs such as gonorrhea and chlamydia, can result in false negatives when mutations occur at the locus targeted by the assay.4 Advanced genomics methods such as whole genome sequencing (WGS) have enabled researchers and health agencies to more effectively monitor novel resistance variants not detected by other methods, and identify specific diagnostic escape mechanisms, which can guide the development of more robust NAAT assays. Similarly to the ongoing surveillance of COVID-19 variants, surveillance of resistant STI strains will benefit from increasing sequencing capacity, targeted sampling strategies and sharing of sequencing data amongst the global scientific community.5 Leveraging automation can provide increased efficiency and accuracy in both diagnosing STIs and tracking antimicrobial resistance, and labs can also utilize their laboratory information management systems (LIMS) to gain greater insights from their data, monitor trends and report data more easily.
“Laboratories commonly face additional challenges such as contamination, technical errors and lack of sample traceability,” Heckler explained. “High-throughput automated solutions will reduce the risk while also meeting demand and providing accurate results. For instance, next-generation sequencing (NGS) will be critical for manufacturers and laboratories to identify these new strains.”
Addressing Social Barriers to Testing
A persistent obstacle to monitoring and managing the spread of STIs has been the social stigma toward STI diagnoses and toward discussions of sex and sexual health in general. Patients may be reluctant to talk to their medical provider about their sexual activity, which could prevent them from requesting an STI test even if they suspect they have been exposed. While destigmatizing sexual health is the ultimate goal, approaches that recognize the current social barriers can help increase testing rates and ensure more people get the treatment they need. A direct-to-consumer (DTC) testing model is one potential approach that could prove beneficial in expanding testing and overcoming stigma.
“During the COVID-19 pandemic, direct-to-consumer (DTC) testing became more popular due to the emergence of home collection devices. Point-of-care devices/testing for COVID-19 have also been adapted to STI detections,” explained Stock. “We anticipate that DTC testing for STIs will develop further due to advances in home collection techniques, better consumer understanding of laboratory testing results, and increased knowledge of the role and importance of clinical diagnostics.”
A DTC testing model could have multiple benefits in addition to increased comfort and privacy for patients. Staff shortages in healthcare can also be a barrier to routine STI screening efforts; self-collected at-home tests can lighten the burden and make regular STI testing more feasible.6 At-home testing options can also alleviate concerns related to in-person activities during the ongoing pandemic, and due to the convenience of testing at home, compared to traveling to a clinic or doctor’s office for testing, more asymptomatic individuals may be encouraged to test themselves regularly.
“DTC for STI testing is more appealing to individuals who find it uncomfortable to discuss these diseases and their sexual history with a clinician. DTC may facilitate routine STI screening, for it requires less time and personnel. Furthermore, DTC tests can help public health labs to perform surveillance to control the spread of STIs,” said Stock.
Direct-to-consumer testing approaches are not without their own challenges – for example, self-collection by an untrained individual may lead to errors and inaccurate results. Additionally, consumers must be informed about the proper type of test kit to use for their situation, the reliability and validity of different offerings, and how to interpret, report and discuss results with their healthcare provider. According to the American Sexually Transmitted Diseases Association (ASTDA), unnecessary overtesting, use of products without clear performance data, and failure to report results or seek confirmatory testing are some of the potential disadvantages of at-home STI testing that should be addressed in order to strengthen the positive impact of DTC testing services on public health.
“There are generally two options for DTC testing: self-collection and self-testing. Self-collection requires a plan in place where a medical professional assesses the results and provides the appropriate diagnosis and treatment. Meanwhile, self-testing may cause inaccuracies due to processing errors or technical challenges common to rapid testing techniques,” explained Stock. “Patients are encouraged to confirm positive self-testing results through a healthcare professional to receive appropriate care and treatment and ensure infections are managed appropriately based on public health guidance.”
The ASTDA recommends that licensing and accreditation requirements for DTC testing services be strengthened to ensure “rigorous validation of assay reliability and quality of services”; this validation data should also be made readily available to both consumers and healthcare providers so they can make informed decisions regarding DTC tests, according to the ASTDA.6 The association also recommends that information related to DTC testing be presented in a consumer-friendly, multilingual format and that population warnings (such as guidance for pregnant women) be clearly communicated to consumers. Moving forward, the organization seeks collaborations with national health agencies, such as the Food and Drug Administration (FDA), and industry to develop clearer guidance and regulations for the validation and verification of DTC testing, handling of self-collected and shipped samples, and STI reporting processes in light of evolving testing strategies.
“From the consumers’ perspective, education is necessary for both DTC approaches to highlight the importance of proper sample collection, doctor mediated interpretation of test results, and treating STIs efficiently,” said Stock. “Additionally, measures are required to ensure patients follow the treatment, and that information on risk reduction and contact tracing is provided.”
References
- Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance: Preliminary 2021 Data. Atlanta: US Department of Health and Human Services; 2022. https://www.cdc.gov/std/statistics/2021/default.htm
- Drug-Resistant Gonorrhea - STD information from CDC. https://www.cdc.gov/std/gonorrhea/arg/default.htm. October 6, 2022.
- "Multi-drug resistant gonorrhoea," Fact Sheet, World Health Organization (2022). https://www.who.int/news-room/fact-sheets/detail/multi-drug-resistant-gonorrhoea
- Allison L Hicks, Stephen M Kissler, Tatum D Mortimer, Kevin C Ma, George Taiaroa, Melinda Ashcroft, Deborah A Williamson, Marc Lipsitch, Yonatan H Grad (2020) Targeted surveillance strategies for efficient detection of novel antibiotic resistance variants eLife 9:e56367. https://doi.org/10.7554/eLife.56367
- World Health Organization. (2021). Guidance for surveillance of SARS-CoV-2 variants: Interim guidance, 9 August 2021. https://www.who.int/publications/i/item/WHO_2019-nCoV_surveillance_variants#cms
- Exten, Cara PhD, MPH; Pinto, Casey N. PhD, MPH, CRNP; Gaynor, Anne M. PhD; Meyerson, Beth MDiv, PhD; Griner, Stacey B. PhD, MPH, CPH; Van Der Pol, Barbara PhD, MPH; on behalf of the Board of Directors of the American Sexually Transmitted Diseases Association. Direct-to-Consumer Sexually Transmitted Infection Testing Services: A Position Statement from the American Sexually Transmitted Diseases Association. Sexually Transmitted Diseases: November 2021 - Volume 48 - Issue 11 - p e155-e159 doi: 10.1097/OLQ.0000000000001475