Point-of-care testing and its implications for STIs

Sexually transmitted infections (STIs) incorporate a particular set of clinical infection and disease processes typically associated with transmission through sexual activity. In 2010, the United States spent approximately $15.6 billion on identification and treatment of STIs.¹ In addition, in 2013, according to Tucker et al “the WHO estimated 448 million new cases of curable sexually transmitted infections…are diagnosed each year.”² The testing traditionally performed by laboratory personnel is thorough, but hours or days are often required to obtain the results. This testing capability usually requires a secondary level medical facility or higher, but that level of care is difficult for many patients to obtain in outlying or rural areas and requires multiple appointments for the patient to be tested and receive results. However, several recent advancements in sexually transmitted infection (STI) detection using point-of-care testing (POCT) have enabled many medical facilities to reduce the number of physician visits, speed up turnaround times, and accurately treat patients in most parts of the country.

The classical STIs are Chlamydia trachomatis (chlamydia), Neisseria gonorrhoeae (gonorrhea), Trichomonas vaginalis (trichomonas), human immunodeficiency virus (HIV), syphilis, human papillomavirus (HPV), and herpes simplex virus (HSV). The most common of these (chlamydia, gonorrhea, and trichomonas) typically require a gram stain and wet mount preparation to be examined by a trained microbiology technician, a culture requiring 72 hours or more and special incubation demands. Due to the analytical time requirements, patients typically have to wait many hours and in most cases days prior to starting treatment or receiving care. Laboratory analysis for HIV, HBV, and HSV usually requires a blood sample for analysis or additional follow-up procedures, while an HPV determination often utilizes a PAP. All of these tests are performed by laboratorians; however, in recent years POCT capabilities have evolved. Many of these tests can detect or negatively identify STIs, some within an hour or less. This is particularly important in areas with limited access to medical care or with patients who may not return for follow-up appointments.

The most frequently used diagnostic test for chlamydia and gonorrhea is the nucleic acid amplification test (NAAT). NAAT utilizes replication of the genetic material of a bacterium. By increasing the quantity of the bacteria within the testing matrix, it makes the target bacterium more easily detectable. However, recent advances in POCT have made quick, preliminary screening for these pathogens a possibility. These kits typically incorporate internal and external controls and are able to provide results in less than 20 minutes. In some cases the sensitivity and specificity of these POC kits can be poor (some as low as 12 percent3), however. This can be due to specimen contamination with menstrual blood or some noted risks of result reproducibility.³ Some more recently approved POCT kits have demonstrated high sensitivity and reproducibility, making rapid and accurate results beneficial for both urban and rural laboratory utilization.

Trichomonas is responsible for 187 million STIs worldwide, with many patients appearing asymptomatic.⁴ While trichomonas can be manually cultured, it requires special medium, a trained eye, and several days to confirm a negative result. Trichomonas can also be seen in wet mounts and urine microscopy; however, identification can be difficult for inexperienced laboratory personnel. Rapid POC tests for this organism have been developed over the past few years, improving sensitivity and specificity. One example of recent testing capability utilizes an immunochromatographic capillary flow method that detects Trichomonas vaginalis membrane proteins and provides results in less than 10 minutes.⁵ Alternately, the molecular NAAT method for trichomonas was approved by the FDA in the POC setting in October 2015. Some NAAT methods are providing results within 50 minutes and with outstanding sensitivity and specificity.

Though the prevalence of HIV has continued to decrease over the years due to prevention efforts and treatment options, the virus still affects 35 million people worldwide.⁶ There are several POC kits that provide rapid results that are key to reducing undiagnosed infection and targeting prevention efforts. These POC kits include hospital-based testing as well as in-home HIV identification, providing results in less than 20 minutes. Multiple POC platforms allow for early detection of the HIV virus in as few as 12 days after infection by detecting HIV antigens as well as antibodies. In addition to POC sample analysis, recent FDA-approved test kits combine testing for both HIV and syphilis testing within a single specimen.²

Syphilis, caused by the spirochete Treponema pallidum, is responsible for 37 million STIs worldwide and has devastating consequences for pregnant women and their fetuses, including low birth weight, stillbirth, premature birth, and congenital defects.² While the standard for syphilis testing has been the rapid plasma reagin (RPR), additional serologic POC tests have been developed that have a much higher sensitivity than traditional RPR. Updated serum sample analyses demonstrate agreement with RPR results as high as 97.6 percent, although these are not POC platform items. Incorporating previously mentioned duo testing, recent POC kits produce Treponema and HIV results of fingerstick or serum blood samples within 15 minutes.

Human papillomavirus (HPV) affects 63 million worldwide and has been linked as a causative agent to cervical and anal cancer.⁷ While the PAP smear has long been the standard for detecting cervical cancer and HPV, a recent HPV genotyping membrane test has shown tremendous promise and is currently being developed as a POC test. When it is approved for use, clinicians can expect a >99.9 percent HPV detection sensitivity.⁸ Incorporation of POC capabilities will continue to expand ability of laboratory analysis from inside the hospital to outlying clinics and medical treatment locations.

HSV affects a staggering 536 million worldwide, and in addition to causing both genital and oral herpes the virus can cause serious or fatal complications for newborns.⁹ While there are no FDA-cleared POC serologic assays for HSV detection, there have been several recent POC HSV molecular assays developed. These assays enable laboratory testing to rapidly produce results while maintaining sensitivity and specificity. Non-FDA cleared serologic assays are also available outside the United States, including some POC kits that have a sensitivity of >90 percent.

Testing for multiple STDs has been a trademark of in-house clinical laboratory capabilities. Introduction of many of the recent FDA-approved POC platforms has increased availability in more remote areas, bringing expanded capabilities to these more rural locations. In addition, some tests have enabled at-home laboratory procedures to become a reality. This has increased patients’ ability to accomplish screening procedures while not sacrificing sensitivity and specificity. In addition, it will enable laboratories to expand their specialization while ensuring that patients are receiving the testing needed and maintaining the accuracy
expected of the laboratory capabilities.

References

1. Gaydos C, Hardick J. Point of care diagnostics for sexually transmitted infections: perspectives and advances. Expert Review of Anti-infective Therapy. 2014;12(6):657-672.
2. Tucker JD, Bien CH, Peeling RW. Point-of-care testing for sexually transmitted infections: recent advances and implications for disease control. Current Opinion of Infections Disease. 2013;26(1):73-79.
3. van Dommelen L, van Tiel FH, Ouburg S, et al. Alarmingly poor performance in Chlamydia trachomatis point-of-care testing. Sexually Transmitted Infections. 2010;86(5):355-359.
4. World Health Organization. Global incidence and prevalence of selected curable sexually transmitted infections – 2008 Trichomonas. WHO. 2012.
5. Sekisui Diagnostics OSOM Trichomonas Rapid Test. July 2011. http://www.sekisuidiagnostics.com/writable/product_documents/files/osom_trich_181_clsi.pdf.  Accessed January 26, 2016.
6. World Health Organization. Global Health Observatory (GHO) Data: HIV/AIDS. WHO. 2016.
7. Clifford GM, Smith JS, Plummer M, Muñoz N, S Franceschi S.. Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer. 2003;88(1):423-428.
8. Song K , Nimse S, An H. HPV genotyping 9G membrane test: a point-of-care diagnostic platform. Sensors. 2014;14(10):19162-19175.
9. Smith, JS, Robinson NJ. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. J Infect Dis. 2002;86(Suppl 1):s3-s28.