Use of Rapid STI Tests in the Clinical Setting


October 2019 - Vol. 8 No. 9 - Page #2

Rapid tests for the identification of infectious diseases are widely used throughout the world and offer a number of advantages. Although rapid tests for syphilis have been used for over one hundred years,1 the introduction of rapid tests for HIV in the late 1980s set the stage for the availability of a larger number and variety of rapid tests in general.2

In addition, because of the large international market to address the HIV pandemic, manufacturers developed novel technologies to gain a competitive edge, spurring the technology forward. Although the uses and advantages of rapid tests for HIV and syphilis are well established, especially for women in labor, occupational exposure, and in resource-limited countries, their use in clinical settings in the US, including hospitals, reference laboratories, large clinics, and other health care settings is less obvious.

Over the past 30 years, rapid tests have evolved significantly to include combination tests that detect antibodies and antigen simultaneously, and the recent introduction of rapid tests that can detect multiple infectious agents (eg, HIV and syphilis) simultaneously via a single drop of blood. Further, technology has continued to mature, as evidenced by the availability of an FDA-approved test for HIV that provides results in just one minute.

Here we focus on the application of rapid tests for HIV antibody/antigen and those rapid or simple tests to detect syphilis antibodies, and present the challenges that need to be addressed when considering the effective use of tests for sexually transmitted infections (STIs) in hospital departments, emergency departments, and other facilities providing health related services.

Use of Rapid Tests

The use of rapid tests, particularly rapid HIV tests, has gained in popularity since their introduction in the late 1980s, and they have proven to be essential for use in a variety of testing situations. Most notably is their use for quickly identifying occupationally exposed individuals and pregnant women before delivery to minimize transmission through the provision of anti-retroviral therapy within a clinically relevant time frame.3

Rapid HIV tests are likewise indispensable for public health clinics and other point-of-care testing situations (eg, physicians’ offices) to test individuals and provide results immediately, thereby decreasing the significant loss of follow-up that occurs if a person must return to the testing site to receive screening results. Rapid HIV tests also are essential in laboratories (primarily in developing countries) where stable electricity or technical expertise is lacking.2 Similarly, the use of rapid tests for syphilis allows smaller clinics (eg, women’s clinics) to identify asymptomatic persons and provide treatment at the same visit for perinatal care, or in general health clinics whose clients exhibit high risk behavior. With both HIV and syphilis infections, immediate treatment can save lives by minimizing disease transmission to others.

Although rapid tests are simple to perform, manufacturer recommendations (package inserts) must be followed without deviation. Because of their simplicity, users often are less vigilant and assume that some deviation will not affect the accuracy of results; a common misconception. Therefore, all users of rapid tests must be properly trained and monitored for proficiency through a quality assurance proficiency program.

Rapid Test Selection Considerations

The selection of a rapid test for screening individuals depends on a few factors:

  • Test situation: Low-risk versus high-risk populations where positive and negative predictive value indices become important
  • Cost considerations: Some tests are more expensive but offer advantages, such as those that use oral fluid as the sample medium
  • Purpose of testing: The need for a test that detects acute and established HIV infection simultaneously, such as a combination HIV Ag/Ab test
  • Test medium: Oral fluid, finger stick, venous whole blood, serum
  • Test location: Whether the test will be performed in an accredited laboratory or requires CLIA-waived status,4 so it can be performed in a non-laboratory venue

Beyond these factors, methodology also must be taken into account. Rapid test formats include dot-blots (flow through), chromatographic (lateral flow), agglutination and flocculation assays,2,5 and others. In the US, all tests must be FDA approved.

Perhaps the most common question asked about the clinical utility of rapid tests is whether they are as accurate as other conventional tests, such as ELISA? Numerous studies have shown the answer is generally yes for persons with established infection. However, their use for identifying acute infection or those individuals in a state of seroconversion may be less effective than more sensitive technologies such as ELISAs. In the US, the choices for initial (screening) tests include flow through and immunochromatographic for HIV, HBV, HCV; and agglutination/flocculation and immunochromatographic for syphilis. The specifics for each technology is well described in the literature.2,6

Immunochromatographic tests usually require one drop of sample only using a dropper (or calibrated pipette), although some require a second step of adding a buffer or placing the test device in a buffer vial. The sample/buffer migrates along a membrane and reacts with components in the test device to give a red color line at the reaction site, thereby signaling a positive result. Dot-blot assays are similar, but sample and added reagent components flow “through” a membrane and produce a circle (dot) as a reaction line. The test indices (sensitivity and specificity) are equivalent with these methods. However, for personnel who are busy with other health care services, simpler methods with fewer steps and/or more rapid results become important attributes.

Test Methodologies and Future Capabilities

Nearly all of the FDA approved rapid tests for HIV7 can use serum, plasma, whole blood, and finger stick blood, and two other rapid tests can use oral fluid. Most require between 10-25 minutes from introduction of the sample until results are generated. Tests that use oral fluids obtained from a swab of the oral cavity eliminate the need for acquiring blood, but they are usually more expensive.

Until recently, all screening tests for syphilis, including the venereal disease research laboratory (VDRL) test and the rapid plasma reagin test (RPR), required instrumentation (ie, a rotator) and expertise in reading agglutination or flocculation tests (these tests are still in use in major laboratories). However, with the introduction of immunochromatographic tests for specific Treponemal antibodies, instrumentation is no longer required, and these tests can be performed by a larger variety of personnel.

In the near future we are expecting the release of multiplex rapid assays capable of detecting more than one infectious agent at a time. One test8 will offer the detection of HIV and syphilis simultaneously, using a single drop of blood from a finger stick, whole blood, or serum specimen, and is read with a small reader to help eliminate subjectivity.9 This test is currently under review for approval by the FDA.

Confirming Infection

The results from all screening tests, including rapid tests for HIV, syphilis, hepatitis B (HBV), and hepatitis C (HCV), must be confirmed using a test with a higher specificity. These confirmatory strategies are not presently configured to be used in non-laboratory settings because they require instrumentation and/or a higher level of training and expertise. Accordingly, for these settings, a sample yielding a positive result by a screening test must be sent to an appropriate reference or clinical laboratory for further testing.

Use of Rapid Tests in Hospitals and EDs

The major barrier for these testing venues is time and personnel availability. Currently, rapid HIV assays used in clinical laboratories are reserved for those situations where there is little choice, such as occupational exposure cases or pregnant women in labor. In most cases, these situations are addressed by first informing the laboratory that a blood sample with suspected HIV will be submitted within the next 30-60 minutes as an alert. When the sample arrives, a dedicated technologist must perform the rapid test and report the results to the submitter as soon as possible; a process that may require the technologist to stop routine activities and spend up to one hour to process, test, and record and transmit the results. Subsequently, the blood sample may be confirmed by another test (ie, ELISA) or sent out to a reference laboratory. When available, those results are transmitted to the submitter for post-test counseling and modification of the treatment strategy, if necessary.

For syphilis testing, most clinical laboratories perform the RPR screening test on plasma or the VDRL on spinal fluid, but the situation is less urgent, and results can be transmitted after confirmation (although screening test results are usually sent immediately). Rapid tests for HBV and HCV are not currently used in clinical laboratories because of the rarity of need for urgent results. When urgent, such as in transplantation patients who cannot be transplanted without a result, ELISA tests for those infections may be performed on a stat basis, rather than keep an inventory of rapid tests for this purpose.

HIV testing has been considered in EDs mainly due to the fact that a large number of patients seek care there, often spend a considerable amount of time waiting for care, and may be high-risk individuals. Thus, implementing rapid testing/screening in this environment is attractive. However, such a program would require dedicated personnel trained in both emergency and laboratory medicine to perform additional activities in an already hectic environment. These dilemmas are difficult to address without readily available resources; an uncommon situation in most hospitals.

For quality assurance, laboratories often track the number of rapid tests performed, results turnaround times, and the burden of interrupted routine activities (based on personal observation and experience).

Conclusion

In summary, rapid testing for STIs is valuable in many testing venues, but to maximize their utility in centralized health care venues, including hospitals and emergency departments, resources must be made available to address the barriers of time and personnel availability.


References

  1. Harris A, Riedel LM. A microflocculation test for syphilis using cardiolipin antigen; preliminary report. J Vener Dis Inform. 1946;27(7): 169-174.
  2. Constantine NT, Saville RD, Dax EM. Retroviral Testing and Quality Assurance: Essentials for Laboratory Diagnosis. MedMira Laboratories, 2005.
  3. Panlilio AL, Cardo DM, Grohskopf LA, et al. Updated US Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis. US Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report; 2013 Update. Accessed 9.25.19. https://stacks.cdc.gov/view/cdc/20711
  4. US CDC. How to Obtain a CLIA Certificate of Waiver. Accessed: 9.24.2019. https://www.cdc.gov/hiv/testing/nonclinical/clia.html
  5. Anfossi L, Giovannoli C, Baggiani C. Introductory Chapter: Rapid Test – Advances in Design, Formats, and Detection Strategies. Intechopen.com. September 26, 2018. Accessed 9.25.19. https://www.intechopen.com/books/rapid-test-advances-in-design-format-and-diagnostic-applications/introductory-chapter-rapid-test-advances-in-design-formats-and-detection-strategies
  6. US Food & Drug Administration. Complete List of Donor Screening Assays for Infectious Agents and HIV Diagnostic Assays. Anit-T. pallidum Assays and other serological tests for Syphilis. Accessed 9.24.19. https://www.fda.gov/vaccines-blood-biologics/complete-list-donor-screening-assays-infectious-agents-and-hiv-diagnostic-assays#anti_Tpallidum_Assays
  7. US FDA. Complete List of Donor Screening Assays for Infectious Agents and HIV Diagnostic Assays. Accessed 9.25.19. https://www.fda.gov/vaccines-blood-biologics/complete-list-donor-screening-assays-infectious-agents-and-hiv-diagnostic-assays
  8. Chembio Diagnostics Systems, Inc. Accessed 9.23.2019. chembio.com
  9. Constantine NT, et al. A New Generation of Rapid Assays: Detection of HIV and Syphilis Simultaneously. HIV Diagnostics Conference. October 2018, Baltimore, MD.

Niel T. Constantine, PhD, MT(ASCP), is a professor in the Department of Pathology at the Institute of Human Virology (IHV), University of Maryland School of Medicine. He was appointed Director of the Clinical Immunology Laboratory at the University of Maryland Medical Center in 1990 where he remained until 2016. At the IHV, his group provides serologic and molecular testing capabilities to staff, performs research activities for the development of new test technologies, provides training for international students, and supports a variety of ancillary activities including sample archiving, quality assurance support, and FDA clinical trials.

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