Sexually transmitted infections: The silent epidemic
[Article 1] Navigating the world of STIs
Sexually transmitted infections (STIs) are infectious diseases that are predominantly spread from person to person through unprotected sexual encounters including oral, anal, and vaginal sex.1 Scientists have established that approximately 30 bacterial, viral, and parasitic pathogens cause these infections with the majority of STI cases being asymptomatic.2 The World Health Organization estimates that almost a million people globally become infected with gonorrhea, chlamydia, trichomoniasis, or syphilis every day, and they expect that these rates will continue to rise unless countries improve their STI prevention, screening, diagnosis, and treatment strategies.3
Common STI-causing pathogens
Scientists consider Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, and Mycoplasma genitalium the most prevalent bacterial STI pathogens and are the causative agents of chlamydia, gonorrhea, syphilis, and M. genitalium infection, respectively.1 Although physicians treat bacterial STIs with antibiotics, the number of antimicrobial resistant (AMR) strains, particularly N. gonorrhoeae and M. genitalium, threatens the clearance of these conditions from patients and their communities. However, scientists can employ antimicrobial susceptibility testing or established molecular tests to assess a bacterial pathogen’s AMR profile.2
In addition to bacterial STIs, the most reported viral STI-causing pathogens include herpes simplex virus and human papillomavirus (HPV), while the protozoan Trichomonas vaginalis is the most common parasitic pathogen and causes trichomoniasis.1 To treat patients with viral and parasitic STIs, physicians often prescribe antivirals or antiprotozoal agents, respectively. Moreover, most country’s public health agencies, such as the Centers for Disease Control and Prevention, recommend that children and young adults receive HPV vaccination to help prevent future infections and the associated increased risk of cancer development.1
Diagnostic testing methods for STIs
Clinicians currently use microscopy, culturing, immunoassays, nucleic acid amplification tests (NAATs), and next-generation sequencing to diagnose their patients with STIs and determine an ideal treatment.
Physicians can directly and rapidly assess patient samples for potential pathogens by using differential staining techniques, such as Gram or Giemsa staining, and microscopic analysis.4 However, the success of these methods depend on the tester’s competency and the pathogen levels within the sample.2 Additionally, scientists are unable to visualize viral particles using light microscopes and instead rely on looking for infection-induced morphological changes to patient cells.
Scientists can also isolate pathogens from patient samples and culture them using specific media. This increases the pathogen’s concentration and allows them to perform additional testing, including microscopic analysis, matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry, or using differential and selective media to identify the organism infecting the patient, as well as perform antimicrobial susceptibility testing.2 But culturing the pathogen and running these additional assessments is time-consuming and takes from a couple of days to several months depending on the organism’s growth rate.5 Additionally, some STI pathogens are difficult to grow in culture.
Clinicians employ immunoassays to directly detect a pathogen’s antigens or a patient’s antibodies against the infecting organism.2 Although this method allows them to specifically identify some pathogens, immunoassays are not available for all STIs. Furthermore, most assays are unable to differentiate between antibodies produced because of a current infection or resulting from past exposures to the pathogen.
NAATs enable scientists to sensitively and accurately detect pathogen-specific nucleic acid sequences within patient samples and include techniques such as quantitative polymerase chain reaction or isothermal amplification assays.2 Because the methods amplify the chosen DNA fragments, clinicians can directly analyze patient samples with low pathogen levels, such as observed during early infection, without requiring them to culture the organisms. This helps save time and allows them to examine difficult-to-culture, slow-growing, or uncultivable microbes. Additionally, they can also use these sensitive and specific molecular tests to examine a pathogen’s AMR profile.2 However, these tests require prior knowledge of the resistance genes and may not be accessible to all countries because of reagent and equipment costs.
Using metagenomic sequencing, scientists can identify all of the pathogens present within a sample and detect the organisms’ AMR genes and mutations. However, most NGS-based methods are expensive and require specialized equipment and extensive training, which can limit their universal application as diagnostic tools.
References
1. Garcia MR, et al. Sexually Transmitted Infections. In: StatPearls. StatPearls Publishing; 2024.
2. Caruso G, et al. Current and future trends in the laboratory diagnosis of sexually transmitted infections. Int J Environ Res Public Health. 2021;18(3):1038.
3. Unemo M, et al. Sexually transmitted infections: Challenges ahead. Lancet Infect Dis. 2017;17(8):e235-e279.
4. Muralidhar S. Molecular methods in the laboratory diagnosis of sexually transmitted infections. Indian J Sex Transm Dis AIDS. 2015;36(1):9-17.
5. Rentschler S, et al. Emerging options for the diagnosis of bacterial infections and the characterization of antimicrobial resistance. Int J Mol Sci. 2021;22(1):456.
[Infographic] Decoding STI testing: A comparison of diagnostic techniques
This infographic visually compares the normal timeframes required for each STI diagnostic technique including direct microscopy, culture-dependent testing, immunoassays, sequencing, and qPCR. It also includes icons depicting key steps in each process.
Sexually transmitted infection (STI) pathogens
Microscopy
Slide preparation and staining
~10 min
Microscopy
Culture-based methods
Growing pathogen(s) in culture
1-180 days
Microscopy
20-60 min
Differential and selective media
1-3 days
MALDI-TOF mass spectrometry
Several min1
Immunoassay
Preparation
0.5-1 h
Immunoassay
2-4 h2
Data analysis
qPCR assay
Preparation
2-6 h1
qPCR
0.5-2 h1
Data analysis
Sequencing
Preparation
Metagenomic sequencing
Data analysis
14-20 h1
References
1. Rentschler S, et al. Emerging options for the diagnosis of bacterial infections and the characterization of antimicrobial resistance. Int J Mol Sci. 2021;22(1):456.
2. Wang D, et al. Recent advances in immunoassay technologies for the detection of human coronavirus infections. Front Cell Infect Microbiol. 2023;12.
[Article 2] STI screening: From challenge to triumph
Early detection of sexually transmitted infections (STIs) helps ensure that patients receive appropriate treatments quickly and helps reduce STI transmission through communities. This is vital because these infections can cause severe, life-threatening complications in untreated patients including pelvic inflammatory disease, ectopic pregnancies, neurological disorders, infertility, cardiovascular diseases, and cancer.1 Moreover, patients with STIs are at an increased risk of acquiring human immunodeficiency virus (HIV). An accurate diagnosis is also essential because inappropriate antimicrobial use, such as prescribing antibiotics for patients with viral STIs, contributes to the rise of antimicrobial resistance genes and strains in a population.2 Now in the post-antibiotic era, this is particularly important as there are few novel antibiotics in development.
STI diagnosis challenges
Although early detection is critical, accurately diagnosing patients is often difficult for physicians because many people suffering from STIs present no symptoms or nonspecific indicators that overlap with other conditions. Further complicating this process, coinfections with multiple STIs are becoming increasingly prevalent, which makes diagnostic testing more difficult and time-consuming if scientists need to run separate tests for each pathogen suspected.3
To overcome these challenges, physicians should routinely screen their patients for STIs using one of the many sensitive and non-invasive testing methods available to them. Because some of these techniques are compatible with multiplexing, such as immunoassays and PCR analyses, this allows clinicians to detect dozens of STI pathogens simultaneously, which helps improve diagnostic efficiency and enables physicians to prescribe treatments for all organisms infecting the patient.
STIs in the news
Recently, STIs have been a hot topic among the public and have been the focus of several breaking news headlines.
Increasing prevalence of neurosyphilis cases among patients without HIV
Scientists consider syphilis the great imitator because of its propensity to produce a variety of symptoms affecting multiple organs.4 While most people have learned about its classical indicators, such as genital ulcers and a rash on the hands and feet, few have heard of symptoms affecting the eyes, ears, and brain. Known as neurosyphilis, this infection of the central nervous system is a consequence of untreated syphilis infections and leads to manifestations including eye sensitivity, vision changes, hearing loss, tinnitus, headaches, and personality changes.5 Researchers most often observe neurosyphilis in patients with HIV. However, Amy Nham, a health scientist from the Centers for Disease Control and Prevention (CDC), recently found evidence to the contrary. Through her presentation at the 2024 Epidemic Intelligence Service Conference, Nham revealed that Chicago clinicians reported an increase in neurosyphilis cases without HIV.6 After examining medical records between January and July 2023, they determined that 68% of patients with neurosyphilis did not exhibit the typical syphilis symptoms and only a third of the cases were also infected with HIV. These results suggest that clinicians should test patients with neurological, ocular, or otic symptoms for neurosyphilis whether or not they have HIV or any of the classical manifestations.
The surge in congenital syphilis rates
Pregnant women with untreated syphilis have an 80% risk of passing their infection on to their fetuses.7 Although congenital syphilis is completely preventable if physicians screen women during their pregnancies and prescribe them antibiotic treatment, the CDC has reported a 755% increase in cases from 2012 to 2021 within the US, and the condition is also on the rise in many other countries including Canada and Japan.7,8 Unless the entire world prioritizes congenital syphilis screening, these rates will continue to grow and threaten the lives of more infants and their mothers.
The link between herpes and dementia
Researchers have found conflicting evidence about the association between herpes simplex virus (HSV) infection and dementia development. But new results from scientists in Sweden suggest that older adults previously infected with HSV have twice the risk of developing dementia compared to age-matched, uninfected people.9 These results highlight the need for controlled clinical studies testing whether antiviral medications used to treat the initial HSV infection could potentially prevent patients from developing dementia in the future.
References
1. Unemo M, et al. Sexually transmitted infections: Challenges ahead. Lancet Infect Dis. 2017;17(8):e235-e279.
2. Otaigbe II, Elikwu CJ. Drivers of inappropriate antibiotic use in low- and middle-income countries. JAC-Antimicrob Resist. 2023;5(3):dlad062.
3. Lee SJ, et al. Coinfections with multiple sexually transmitted pathogens in Republic of Korea, 2018–2020. J Clin Lab Anal. 2022;36(10):e24682.
4. Tudor ME, et al. Syphilis. In: StatPearls. StatPearls Publishing; 2024.
5. Ha T, et al. Neurosyphilis. In: StatPearls. StatPearls Publishing; 2024.
6. Nham A, et al. Neurosyphilis, Ocular, and Otic Syphilis Cases - Chicago, Illinois, January-August 2023. Presented at: 2024 Epidemic Intelligence Service Conference; Atlanta, GA; 2024.
7. David A, et al. Congenital syphilis in Switzerland: A marker of inequality? A mini-review. Front Public Health. 2023;11:1265725.
8. McDonald R, et al. Vital signs: Missed opportunities for preventing congenital syphilis - United states, 2022. MMWR Morb Mortal Wkly Rep. 2023;72.
9. Vestin E, et al. Herpes simplex viral infection doubles the risk of dementia in a contemporary cohort of older adults: A prospective study. J Alzheimers Dis. 2024;97(4):1841-1850.
[Article 3] Breaking the stigma to improve STI diagnosis and treatment
Barbara Van Der Pol, PhD, MPH
Professor of Medicine and Public Health
University of Alabama at Birmingham (UAB)
Director, UAB STD Diagnostics Laboratory
In 1982, Barbara Van Der Pol began studying a virtually unknown sexually transmitted infection (STI), chlamydia. At the time, only specialty laboratories could detect the bacterial pathogen and consequently, this infection would often remain untreated. However, Van Der Pol and her colleagues helped highlight the importance of its diagnosis after determining that untreated chlamydial infections in women frequently lead to later complications including pelvic inflammatory disease and infertility. This research spurred her interest in STIs and their devastating effects on women’s health. Over 40 years later, Van Der Pol continues to investigate these stigmatized and often dismissed infections as a professor of medicine and public health at the University of Alabama at Birmingham.
What makes STIs a threat to public health globally?
There are a lot of reasons. STIs can cause increased infertility rates and adverse outcomes during pregnancy including low birth weights, premature rupture of membranes, early delivery, and in the case of syphilis, congenital abnormalities. For both men and women, these infections increase their risk of acquiring human immunodeficiency virus (HIV). Because HIV infections require lifelong management, it is quite expensive for the healthcare system to help these patients. Additionally, bacterial vaginosis (BV), which is a condition characterized by an imbalance in the vaginal microbiome, is a very common problem that women face. Scientists have determined that BV increases a woman’s risk of acquiring an STI and as a result, this condition economically strains the healthcare system. Most importantly, everybody has a right to enjoy a happy, healthy sexuality free of disease.
Why is it difficult to examine STI epidemiology?
STI epidemiology is challenging to study because it is hard to determine when people become exposed to these pathogens. Unlike other infectious diseases, such as COVID-19, where scientists can determine when and where they acquired the infection and the outcome, STIs are silent diseases affecting private areas of the body. Herpes is a great example. Someone can test positive for herpes antibodies today, but physicians do not know if they acquired the virus years ago or yesterday. Differentiating between a disease’s incidence, which is the number of new cases, and prevalence, which is the number of existing cases, is difficult and that makes its epidemiology hard to understand.
But the other piece of this is that these infections are so stigmatized that people do not want to report them. For example, every state in the US requires that both the physician and laboratory report STI cases. However, many physicians do not bother likely because they do not want to turn their patients in and instead, want that guilt to fall to the laboratory. Also, patients do not want to talk about their private business with their physicians, but this prevents scientists from accurately studying the epidemiology of these infections.
In a recent paper, you examined how frequently physicians test patients for both vaginitis and STIs.1 Why is this co-testing important?
When a woman comes into a clinic with symptoms including vaginal discharge or a burning sensation when urinating, most physicians will test their patient for either an STI or vaginitis—a condition identified by vaginal inflammation that is commonly caused by BV. Although both ailments share these same symptoms and spread in the same manner, physicians often make this decision based on their judgment of the woman as a person including what population she is from and her perceived behavior. Additionally, only 40% of women with BV have this condition alone, while the other 60% are also infected with at least one STI-causing pathogen, such as Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis. This means that many women are not receiving treatment for all of the conditions afflicting them. Through this paper, we tried to highlight the importance of employing diagnostic methods, such as molecular testing, which can accurately distinguish between BV and STIs and ensure that patients are receiving the comprehensive healthcare services they deserve.
This interview has been condensed and edited for clarity.
References
1. Pinto CN, et al. Differential screening for nonviral sexually transmitted infections by type of vaginitis testing. Sex Transm Dis. 2023;50(8):531.
Resources
[Panel 1] STI Testing & Market Trends: Insights on Panels & Utilization
Dr. Vijay Singh
Vice President, Research and Development
HealthTrackRx
Discover more about STIs and their impact on sexual health, where Dr. Singh will share his expertise surrounding the wide range of pathogens causing STIs and the associated medical challenges. He will also delve into the pressing issue of antimicrobial resistance and the need for improved treatment approaches. Enhance your knowledge of STI testing options, with a focus on highly accurate molecular diagnostics like PCR, in this informative presentation.
Watch now
[Panel 2] Validating a Multiplex STI Panel With Non-Invasive Sample Types
Dr. Vijay Singh
Vice President, Research and Development
HealthTrackRx
Sexually transmitted infections (STIs) represent a unique healthcare burden in the United States with over 20 million new cases every year and an urgent need to control the spread. A multiplex PCR approach to STI testing has emerged as an economical and broader approach to routine STI and urgent STI testing. However, a practical challenge of implementing an STI multiplex panel is validation.
Dr. Vijay Singh continues discussion in this webinar that focuses on adapting to and validating a single assay for four commonly requested STI tests: Chlamydia trachomatis (CT), Neisseria gonorrhea (NG), Mycoplasma genitalium (MG), and Trichomonas vaginalis (TV), using two separate PCR platforms and non-invasive sample types.
Watch now
[Panel 3] Addressing the Rising STI Epidemic
Cyndi Clark, PhD
Sr. Scientific Consultant, Biopharma
Aegis Sciences Corporation
Sexually transmitted infections (STIs) are a growing global concern, with an estimated 1 million new cases acquired each day worldwide. The need for effective STI testing has never been more urgent.
In our latest blog post, we highlight the significance of STI testing and its role in optimizing surveillance and identification of potential outbreaks. More specifically, Cyndi Clark, PhD, Senior Scientific Consultant, Biopharma, with Aegis Sciences Corporation, discusses the value of multiplex PCR tests for STI diagnosis.
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[Panel 4] Sexually Transmitted Infections: Get the Facts
More than 30 pathogens—including bacteria, viruses, and parasites—are known to cause sexually transmitted infections (STIs). [1] STIs are threats to sexual and reproductive health due to associated medical problems. [1,2]
In addition, antimicrobial resistance among STIs has become a public health crisis that calls for improved antimicrobial stewardship and treatment optimizations. [3,4]
There are several common testing options for STIs. Of these, molecular diagnostics (MDX) such as PCR, have shown higher sensitivity and specificity than culture-based methods, allowing more accurate detection.
Read now
References
- World Health Organization (WHO). “Sexually Transmitted Infections (STIs).” World Health Organization. World Health Organization, August 22, 2022.
- Unemo M, Bradshaw CS, Hocking JS, et al. Sexually transmitted infections: challenges ahead. Lancet Infect Dis. 2017;17(8):e235-e279.
- Seña AC, Bachmann L, Johnston C, et al. Optimising treatments for sexually transmitted infections: surveillance, pharmacokinetics and pharmacodynamics, therapeutic strategies, and molecular resistance prediction. Lancet Infect Dis. 2020;20(8):e181-e191. doi:10.1016/S1473-3099(20)30171-7.
- Baumann L, Cina M, Egli-Gany D, et al. Prevalence of Mycoplasma genitalium in different population groups: systematic review and meta-analysis. Sex Transm Infect. 2018;94(4):255-262. doi:10.1136/sextrans-2017-053384.
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