FDA has recently granted marketing clearance to Hologic Inc, Marlborough, Mass, for the company’s Aptima Mycoplasma genitalium assay. This is the first test authorized by FDA to test for the M. genitalium bacterium, a sexually transmitted infection (STI) that is associated with inflammation of the urethra (non-gonococcal urethritis) in men, and inflammation of the cervix (cervicitis) and infection of the reproductive organs (pelvic inflammatory disease) in women.
“Patients with unidentified urogenital infections are typically treated with antibiotics, some of which may not be effective against M. genitalium,” says FDA Commissioner Scott Gottlieb, MD. “In the past, it has been hard to diagnose this organism. By being able to detect it more reliably, doctors may be able to more carefully tailor treatment and use medicines most likely to be effective.
“In cases where M. genitalium is detected, doctors can consider forgoing use of antibiotics that are known to be ineffective against M. genitalium and choose a treatment more likely to be appropriate,” adds Gottlieb. “Having accurate and reliable tests to identify the specific bacteria that’s causing an infection can assist doctors in choosing the right treatment for the right infection, which can reduce overuse of antibiotics and help in the fight against antimicrobial resistance.”
First discovered in the early 1980s, M. genitalium was listed as an emerging public health threat by the US Centers for Disease Control and Prevention (CDC) in 2015.1,2 In the United States, according to CDC, M. genitalium is responsible for causing approximately 15% to 30% of persistent or recurrent urethritis cases in men, and 10% to 30% of cervicitis cases in women. Current estimates indicate that prevalence of M. genitalium is increasing.3
M. genitalium is a slow-growing bacterium and is difficult to detect with traditional laboratory methods. Because of the lack of an FDA-cleared test until now, M. genitalium has often been misdiagnosed as other STIs and, in some cases, treated with the wrong antibiotics. This often leaves the underlying infection untreated, which can lead to increased transmission and recurrent infections.
The Aptima M. genitalium assay is a nucleic acid amplification test that detects M. genitalium in urine, urethral, penile meatal, endocervical, or vaginal swab samples collected in a clinical setting, such as a doctor’s office or clinic.
“Although M. genitalium is typically more common than gonorrhea, there is very little public awareness of this rising sexually transmitted infection, which can cause serious and potentially devastating health problems,” says Damon Getman, PhD, senior principal research scientist and director of research at Hologic. “Introduction of the Aptima M. genitalium assay gives healthcare professionals the opportunity to provide optimal care for their patients and reflects Hologic’s commitment to developing innovative solutions that address emerging public health threats.”
In men, M. genitalium symptoms may include urethritis, the swelling and inflammation of the urethra. In women, M. genitalium has been linked to cervicitis, the swelling and inflammation of the cervix.4,5 If left untreated, infections can lead to infertility in women and increased risk of HIV acquisition and transmission.2,6 Patients infected with M. genitalium may be asymptomatic or experience symptoms similar to those associated with a chlamydial infection, so accurate diagnostic tests are critical to help healthcare professionals and their laboratory partners identify these bacterial infections and treat them appropriately. Research has shown as many as 50% of women and 42% of men with M. genitalium may have an antibiotic-resistant strain, further emphasizing the importance of early detection and regular screening.3
“We are tremendously proud of the team of scientists and engineers who developed this assay,” says Tom West, Hologic’s division president for diagnostic solutions. “They exemplify Hologic’s dedication to help arm laboratories and healthcare professionals with superior diagnostic tools to identify harmful infections, and this FDA clearance represents another milestone in furthering that mission.”
In published research, Hologic’s ribosomal RNA-based M. genitalium assay displayed greater sensitivity than lab-developed or CE-marked DNA-based tests.7,8 FDA reviewed data from a clinical study that included testing of 11,774 samples. The study showed that the Aptima M. genitalium assay correctly identified M. genitalium in approximately 90% of vaginal, male urethral, male urine, and penile samples. It correctly identified M. genitalium in female urine and endocervical samples 77.8% of the time and 81.5% of the time, respectively.
Vaginal swabs are the preferred sample type due to better clinical performance. However, alternative sample types, such as urine, can be used if vaginal swabs are not available. In addition, the study showed that the test correctly identified samples that did not have M. genitalium present 97.8% to 99.6% of the time.
FDA reviewed the Aptima M. genitalium assay through its De Novo premarket pathway, a regulatory pathway for low- to moderate-risk devices of a new type. Through its De Novo authorization, FDA established special controls for tests of this type, including requirements for demonstrating the accuracy and reliability of tests intended to be used as an aid in the diagnosis of M. genitalium urogenital infections. The special controls, when met along with general controls, provide a reasonable assurance of safety and effectiveness for tests of this type.
The agency’s action creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through the FDA’s 510(k) premarket process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a predicate device.
Hologic introduced the first FDA-cleared diagnostic test kit for STIs in the 1990s using its innovative RNA-based technology. Since then, Hologic has expanded its Aptima STI portfolio to include assays for chlamydia, gonorrhea, herpes simplex viruses (HSV 1 and 2), human papillomavirus (HPV), and trichomonas. Hologic also offers a Zika virus assay, which is available for use by authorized laboratories under an FDA emergency use authorization.
The Aptima virology portfolio also includes quantitative assays for the human immunodeficiency virus (HIV) and hepatitis B and C (HBV and HCV). All are available on Hologic’s fully-automated Panther system.
Including the first IVD for the detection of M. genitalium, Hologic’s Panther and Panther Fusion system now offers 14 FDA-cleared or approved assays that detect more than 20 pathogens, making it the only high-throughput molecular diagnostic platform in the United States to combine comprehensive sexual health, cervical health, viral load, respiratory testing, and open-channel functionality on a fully automated system. Open channel functionality on the Panther system is a non-IVD function, which is not cleared or approved by FDA.
For more information, visit Hologic.
1. Tully JG, Taylor-Robinson D, Cole RM, Rose DL. A newly discovered mycoplasma in the human urogenital tract. Lancet. 1981;1(8233):1288–1291.
2. 2015 Sexually Transmitted Diseases Treatment Guidelines: Emerging Issues [online]. Atlanta: Centers for Disease Control and Prevention, 2015. Available at: www.cdc.gov/std/tg2015/emerging.htm. Accessed December 7, 2018.
3. Getman D, Jiang A, O’Donnell M, Cohen S. Mycoplasma genitalium prevalence, coinfection, and macrolide antibiotic resistance frequency in a multicenter clinical study cohort in the United States. J Clin Microbiol. 2016;54(9):2278–2283; doi: 10.1128/jcm.01053-16.
4. Horner PJ, Martin DH. Mycoplasma genitalium infection in men. J Infect Dis. 2017;216(Suppl 2):S396–S405; doi: 10.1093/infdis/jix145.
5. Wiesenfeld HC, Manhart LE. Mycoplasma genitalium in women: current knowledge and research priorities for this recently emerged pathogen. J Infect Dis. 2017;216(Suppl 2):S389–S395; doi: 10.1093/infdis/jix198.
6. Gatski M, Martin DH, Theall K, et al. Mycoplasma genitalium infection among HIV-positive women: prevalence, risk factors, and association with vaginal shedding. Int J STD AIDS. 2011;22(3):155–159; doi: 10.1258/ijsa.2010.010320.
7. Unemo M, Salado-Rasmussen K, Hansen M, et al. Clinical and analytical evaluation of the new Aptima Mycoplasma genitalium assay, with data on M. genitalium prevalence and antimicrobial resistance in M. genitalium in Denmark, Norway, and Sweden in 2016. Clin Microbiol Infect. 2018;24(5):533–539; doi: 10.1016/j.cmi.2017.09.006.
8. Le Roy C, Pereyre S, Hénin N, Bébéar C. French prospective clinical evaluation of the Aptima Mycoplasma genitalium CE-IVD assay and macrolide resistance detection using three distinct assays. J Clin Microbiol. 2017;55(11):3194–3200; doi: 10.1128/jcm.00579-17.
Featured image: The Aptima Mycoplasma genitalium assay by Hologic.