NEW YORK – The US Centers for Disease Control and Prevention on Thursday issued an update to its guidelines for the diagnosis and treatment of sexually transmitted infections, including new recommendations for diagnostic testing in certain infections.
The guidelines update 2015 CDC recommendations, which were particularly notable in their introduction of recommendations for nucleic acid amplification tests, or NAATs, for Trichomonas vaginalis and routine trichomonas screening for high-risk populations.
The 2021 CDC STI guidelines now include updated recommendations for the NAAT-based diagnosis of Mycoplasma genitalium, rectal and pharyngeal chlamydia and gonorrhea, as well as new guidance for genital herpes simplex virus and hepatitis C virus testing.
In 2015, the CDC noted that although M. genitalium takes up to six months to grow in culture, the absence of a US Food and Drug Administration-cleared molecular diagnostic test at the time meant the bacterial infection could only be suspected in cases of persistent or recurrent urethritis, cervicitis, and pelvic inflammatory disease, or PID.
Now, in its 2021 guidance, the CDC specifically mentions that an M. genitalium NAAT assay from Hologic is cleared by the FDA for use with urine and urethral, penile meatal, endocervical, and vaginal swab samples.
For diagnosis of the amoeboid parasite T. vaginalis, the guidelines continue to highlight molecular assays, including Hologic's Aptima test, as well as Becton Dickinson's ProbeTec and BD Max TV tests, GeneXpert TV from Cepheid, and Quidel's Solana and AmpliVue TV tests. Non-molecular tests mentioned in the guidance include the Osom trichomonas rapid test from Sekisui Diagnostics, and Affirm VPIII from BD.
The guidelines do not explicitly mention a combined M. genitalium and trichomonas assay from Roche — the Cobas TV/MG test for the detection of T. vaginalis and M. genitalium DNA — which is FDA-cleared for use in symptomatic and asymptomatic patients.
Antimicrobial resistant M. genitalium is also an increasing global concern and focus for diagnostics developers.
The CDC writes in the guidelines, "Molecular tests for macrolide (i.e., azithromycin) or quinolone (i.e., moxifloxacin) resistance markers are not commercially available in the United States," but "molecular assays that incorporate detection of mutations associated with macrolide resistance are under evaluation." Roche also recently partnered with SpeeDx to expand access to antimicrobial-resistant STI assays, which include resistance tests for M. genitalium and Neisseria gonorrhoeae.
The CDC further guides that men with recurrent non-gonococcal urethritis should be tested for M. genitalium "using an FDA-cleared NAAT," and "if resistance testing is available, it should be performed and the results used to guide therapy."
Women with recurrent cervicitis should also be tested for M. genitalium, and testing should be considered among women with PID, the guidelines now state. "Testing should be accompanied with resistance testing, if available."
Screening of asymptomatic M. genitalium infection among women and men or extragenital testing for M. genitalium is not recommended. In clinical practice, if testing is unavailable, M. genitalium should be suspected in cases of persistent or recurrent urethritis or cervicitis and considered for PID, according to the guidelines.
Gonorrhea infections are on the rise globally, with increasing incidence of antibiotic-resistant strains. In the 2021 guidelines, the CDC highlights that gonorrhea detection using molecular tests is more sensitive than culture-based methods, but sensitivity can vary by anatomical site.
The agency notes that patient-collected samples are "reasonable alternatives to provider-collected swabs for gonorrhea screening by NAAT." The CDC also reiterates recent guidance that ceftriaxone alone be used to treat gonorrhea, rather than dual therapy with ceftriaxone and azithromycin, due to the emergence of azithromycin resistance.
The CDC continues to recommend annual chlamydia and gonorrhea screening for all sexually active women 25 years of age or older. It also recommends testing for gonorrhea and chlamydia by NAAT of urine for men who have had sex with women in the past year. For men who have had sex with men, the agency recommends rectal testing for gonorrhea and chlamydia, and pharyngeal testing for gonorrhea only, using provider-collected or self-collected specimens.
For herpes simplex virus testing, the CDC recommends clinical diagnosis be confirmed by type-specific virologic testing using NAAT or culture for cases in which genital lesions are present.
Type-specific serologic tests can be used to aid in the diagnosis of HSV infection in the absence of genital lesions. The CDC recommends two-step serologic testing for HSV. The guidelines state, "Because of the poor specificity of commercially available type-specific EIAs ... a confirmatory test (Biokit or western blot) with a second method should be performed before test interpretation."
The CDC also guides that if confirmatory tests are unavailable, "patients should be counseled about the limitations of available testing before obtaining serologic tests, and healthcare providers should be aware that false-positive results occur."
The new guidelines also recommend universal hepatitis C testing at least once in a person's lifetime in accordance with previously issued guidance. The testing algorithm requires an antibody test first, with positive results confirmed using an FDA-cleared HCV NAAT.
The 2021 guidance also includes discussion of point-of-care and lab-based molecular tests for bacterial vaginosis.
The agency notes that for BV testing at the point-of-care, a test from Sekisui Diagnostics called Osom BV Blue has utility in certain diagnostic contexts, while the FemExam Test Card from CooperSurgical is not a preferred diagnostic method for BV diagnosis.
The 2015 guidelines recommended BV diagnosis by clinical criteria and Gram staining. At that time, the CDC noted that PCR tests had been used in research settings for the detection of organisms associated with BV, but assessments of clinical utility were still underway.
The updated CDC guidelines now specifically mention five commercially available quantitative multiplex PCR assays for BV: BD's Max Vaginal Panel; Hologic's Aptima BV; NuSwab VG from Laboratory Corporation of America; SureSwab BV from Quest Diagnostics; and the OneSwab BV Panel PCR with Lactobacillus Profiling by qPCR from Medical Diagnostic Laboratories.
The BD and Hologic BV assays are cleared by the FDA, the CDC guidelines further note, while the other three are laboratory-developed tests.
The guidelines recommend these tests be used by symptomatic women only because their accuracy is not well defined for asymptomatic women. They also state that other clinical diagnostic methods — specifically, the Amsel criteria, Nugent score, and the Affirm VPIII assay from BD — continue to have utility in cases of suspected BV due to lower cost and ability to provide a rapid diagnosis.