Current treatment, challenges, and research updates in Sexually Transmitted Infections: A detailed review
Gowdham P
Nursing Educator, Kauvery Hospital, Marathahalli, Bangalore
Abstract
Sexually transmitted infections (STIs) remain a leading global public-health challenge. While effective treatments exist for many bacterial and protozoal STIs and robust prevention (e.g., HPV vaccination, HIV PrEP) has reduced disease burden in some settings, rising antimicrobial resistance (AMR), diagnostic gaps, asymptomatic infection, and access barriers hamper control. This review summarizes up-to-date treatment approaches for common STIs (syphilis, gonorrhoea, chlamydia, Mycoplasma genitalium, trichomoniasis, HSV, HPV, HIV), highlights major clinical and public-health challenges, and reviews ongoing research notably vaccine development efforts (gonorrhoea, syphilis, HSV), novel antimicrobials (e.g., Gepotidacin), doxycycline post-exposure prophylaxis (doxy-PEP), point-of-care molecular diagnostics, and long-acting prevention modalities. We conclude with pragmatic recommendations for clinicians and researchers and identify priority areas for future work.
Introduction
STIs are caused by diverse pathogens (bacteria, viruses, protozoa) and cause acute illness, long-term morbidity (infertility, adverse pregnancy outcomes), and facilitate HIV transmission. Despite prevention tools (HPV vaccine, HIV ART/PrEP) and effective therapeutics, the global STI burden remains high and evolving because of antimicrobial resistance, incomplete uptake of prevention, and diagnostic limitations. Surveillance and updated clinical guidance (WHO, CDC) remain central to management.
Current treatment modules – by infection
- Syphilis (Treponema pallidum)
- First-line therapy: Benzathine penicillin G (single IM dose for early syphilis; regimens differ for late/latent, neurosyphilis). Penicillin remains the only proven therapy for preventing congenital syphilis; pregnant patients allergic to penicillin require desensitization. Current guideline summaries remain unchanged.
| Early syphilis (<1–2 yrs, primary/secondary/early latent) | Recommended | Alternative |
|---|---|---|
| US CDC Guideline | Benzathine penicillin G 2.4M units IM single dose | Doxycycline 100 mg PO q12h ×14 days (or) Ceftriaxone 1–2 g IM q24h ×10 days |
| UK Guideline | Benzathine penicillin G 2.4M units IM single dose (or) Procaine penicillin G 600,000 units IM q24h ×10 days | Doxycycline 100 mg PO q12h ×14 days (or) Erythromycin 500 mg PO q6h ×14 days (or) Ceftriaxone 500 mg IM/IV daily ×10 days (or) Amoxicillin 500 mg PO q6h + Probenecid 500 mg PO q6h ×14 days |
| European Guideline | Benzathine penicillin G 2.4M units IM single dose | Procaine penicillin 600,000 units IM/IV daily ×10–14 days (or) Doxycycline 200 mg PO daily ×14 days (or) Ceftriaxone 500 mg–1 g IM/IV daily ×10 days (or) Azithromycin 2 g PO single dose |
| Late syphilis (>1–2 yrs | Cardiovascular | Gummatous) Recommended Alternative |
|---|---|---|
| US CDC Guideline Benzathine penicillin G 2.4M units IM weekly ×3 weeks Doxycycline 100 mg PO q12h ×28 days | ||
| UK Guideline Benzathine penicillin G 2.4M units IM weekly ×3 weeks (or) Procaine penicillin 600 | 000 units IM q24h ×17 days Doxycycline 100 mg PO q12h ×28 days (or) Amoxicillin 2 g PO q8h + Probenecid 500 mg PO q6h ×28 days | |
| European Guideline Benzathine penicillin G 2.4M units IM weekly ×3 doses Procaine penicillin 600 | 000 units IM/IV daily ×17–21 days (or) Doxycycline 200 mg PO daily ×21–28 days |
| Neurosyphilis | Recommended | Alternative |
|---|---|---|
| US CDC Guideline | Aqueous crystalline penicillin G 3–4M units IV q4h ×10–14 days | Ceftriaxone 2 g IM/IV q24h ×10–14 days |
| UK Guideline | Procaine penicillin 1.8–2.4M units IM q24h + Probenecid 500 mg PO q6h ×17 days (or) Benzyl penicillin 3–4M units IV q4h ×17 days | Doxycycline 200 mg PO q12h ×28 days (or) Amoxicillin 2 g PO q8h + Probenecid 500 mg PO q6h ×28 days (or) Ceftriaxone 2 g IM/IV q24h ×10–14 days |
| European Guideline | Benzyl penicillin 3–4M units IV q4h ×10–14 days | Ceftriaxone 1–2 g IV Daily |
| ×10–14 days (or) | ||
| Procaine penicillin1.2–2.4M units IM daily +Probenecid 500 mg | ||
| PO q6h×10–14days |
- Diagnostics & monitoring: Serologic testing (treponemal + non-treponemal assays) used for diagnosis and treatment response; POCT dual tests expanding access in low-resource settings. Ongoing research seeks vaccine candidates but antigenic complexity and immune evasion present challenges.
2. Gonorrhoea (Neisseria gonorrhoeae)
- Current regimens: In many settings ceftriaxone (IM) remains first-line; guidelines have evolved in dose recommendations and co-treatment approaches. NAATs + culture remain essential for diagnosis and AMR surveillance.
- Antimicrobial resistance & new drugs: Rapidly rising AMR (including reduced susceptibility to cephalosporins and macrolides) threatens treatment. New antimicrobials and oral options are in late-stage development. e.g., gepotidacin showed promising phase-3 results for uncomplicated gonorrhoea and may broaden oral treatment options pending approvals and post-marketing data. Vaccine research (GMMA and other platforms) and repurposing of meningococcal B vaccine effects are active research areas.
3. Chlamydia (Chlamydia trachomatis)
- Preferred therapy: Doxycycline 100 mg PO twice daily for 7 days is now favoured for urogenital chlamydia in many guidelines, particularly for rectal infection where azithromycin shows lower efficacy. Single-dose azithromycin is still used in certain settings but is less recommended for rectal infections. Test-of-cure not required for uncomplicated urogenital infections except in pregnancy or persistent symptoms.
4. Mycoplasma genitalium (MG)
- Management challenges: MG has increasing resistance to macrolides (azithromycin) and fluoroquinolones (moxifloxacin), limiting reliable empiric regimens. Resistance-guided therapy using NAATs with resistance mutation testing is advised where available; this usually involves macrolide or fluoroquinolone selection based on mutation profile, and alternative agents or combination regimens for multidrug resistance. Surveillance shows rising dual resistance in some settings.
5. Trichomoniasis (Trichomonas vaginalis)
- Treatment: Metronidazole or tinidazole (single dose or multiday regimens) remain effective. NAATs have improved diagnostic sensitivity relative to wet mount and culture, improving case detection. Resistance is uncommon but reported.
6. Herpes Simplex Virus (HSV-1/HSV-2)
- Treatment: Acyclovir, valacyclovir, famciclovir for episodic and suppressive therapy; no curative antiviral is approved. Treatment reduces symptoms and viral shedding but does not eliminate latent infection. Research includes therapeutic and prophylactic vaccines, monoclonal antibodies, and experimental gene-editing approaches (e.g., CRISPR/Cas strategies) showing promise in preclinical/early studies.
7. Human Papillomavirus (HPV)
- Management & prevention: No antiviral cures for established HPV infection; lesion-directed therapies (cryotherapy, excision) treat neoplasia. Prophylactic HPV vaccines (2-, 4-, 9-valent) are highly effective at preventing vaccine-type infection and precancerous lesions when given before exposure; vaccine programs are central to cervical cancer prevention. Effectiveness is greatest when vaccination occurs at younger adolescent ages.
8. HIV — prevention and treatment advances
- Treatment: Universal ART with integrase-based regimens (e.g., dolutegravir-based) is standard for HIV treatment.
- Prevention: Oral PrEP and long-acting injectable cabotegravir (Apretude) are major advances; cabotegravir provides an every-2-month option and has regulatory approvals for PrEP in numerous jurisdictions.
Cross-Cutting Clinical and Public-Health Challenges
Antimicrobial Resistance (AMR)
- AMR is the single biggest medical threat to management of bacterial STIs — particularly N. gonorrhoeae and M. genitalium. Loss of reliable oral options complicates outpatient management and increases reliance on parenteral agents and newer (and sometimes costly) antibiotics. Robust surveillance, culture + susceptibility testing, and stewardship are essential.
Diagnostic Gaps & Asymptomatic Infections
- Many STIs are asymptomatic (e.g., chlamydia, early gonorrhea), perpetuating transmission. NAATs and expanded extragenital screening improve detection, but access to sensitive diagnostics is uneven globally. WHO and national agencies emphasize point-of-care molecular testing and simplified algorithms to improve reach.
Access, Stigma, and Health Equity
- Stigma, cost, and healthcare access barriers reduce screening uptake, delay treatment, and impede prevention efforts. Public-health programs must integrate culturally appropriate outreach, confidentiality, and simplified care pathways (e.g., telemedicine, self-sampling) to improve access.
Implementation & Behavioural Factors
- Secondary prevention (partner notification, adherence to therapy, retesting) is crucial but variably implemented. New tools (home testing kits, digital reminders) show promise to improve engagement and re-testing.
Ongoing research & promising advances
New antimicrobials and stewardship strategies
- Gepotidacin and other novel agents have shown positive trial results for gonorrhea and may offer oral options against resistant strains — an important milestone if confirmed across populations and anatomical sites. Sustained stewardship will be required to slow emergence of resistance.
Doxycycline post-exposure prophylaxis (doxy-PEP)
- Doxy-PEP (single 200 mg dose within 72 hours of condomless sex) has been recommended for certain high-risk groups (e.g., MSM, transgender women with recent STIs) after risk–benefit assessment; it reduces chlamydia/gonorrhea/some syphilis but raises concerns about broader resistance selection and impacts on microbiomes. Implementation requires careful local policy decisions and monitoring.
Vaccines — status and prospects
- Gonorrhoea: No licensed gonorrhoea vaccine exists, but observational data suggesting partial protection from meningococcal group B vaccines (4CMenB) has energized vaccine research. Several platforms (GMMA, OMV, protein subunits) are in preclinical/early clinical development; modelling studies consider optimal targeting strategies.
- Syphilis: Syphilis vaccine development lags but is active; candidate antigens (outer membrane proteins), OMV, VLP and mRNA strategies are under exploration. Major obstacles include antigenic variability and immune evasion by Treponema pallidum, requiring translational research and animal model work.
- HSV: A range of prophylactic and therapeutic HSV vaccine candidates have advanced to clinical trials; results to date have been mixed and no vaccine is yet licensed but renewed strategic programs and novel platforms (protein + adjuvant, mRNA) are in progress. Gene-editing research offers another long-term approach for cure strategies and is showing preclinical promise.
- HPV: HPV vaccine programs continue to expand, with evidence of strong real-world effectiveness. Efforts focus on increasing coverage (including single-dose schedules under evaluation), broadening access in low- and middle-income countries, and extending vaccine protection.
Diagnostics & point-of-care testing
WHO and other groups support scaling up affordable point-of-care NAATs and multiplex platforms to permit same-visit diagnosis and treatment. Home-sampling and self-collection kits improve reach and acceptability and are increasingly available in several markets.
Why STI Vaccine Development is Difficult?
Despite decades of research, effective vaccines against most bacterial and viral STIs remain elusive. The difficulties arise from both biological factors of the pathogens and scientific/clinical barriers:
Immune Evasion & Lack of Natural Immunity
- Many STIs (e.g., gonorrhoea, HSV) do not induce long-lasting protective immunity after natural infection; reinfections are common.
- This means the immune system often fails to “remember” the pathogen — making it harder for vaccines to mimic protective immunity.
Antigenic Variability & Strain Diversity
- Neisseria gonorrhoeae rapidly alters its surface proteins (antigenic variation), evading antibodies.
- Treponema pallidum (syphilis) has few surface antigens and hides most of its proteins in the periplasm, shielding them from immune attack.
- HPV has many types; vaccines had to cover multiple high-risk genotypes to be broadly protective.
Latency & Persistence
- HSV establishes latency in nerve ganglia, with intermittent reactivation; no vaccine has been able to fully prevent establishment of latency.
- HIV integrates into host DNA, creating a permanent reservoir, making sterilizing immunity extremely challenging.
Mucosal Immunity Challenges
- Most STIs are transmitted across genital mucosa. Generating strong, durable mucosal IgA and tissue-resident T-cell responses through vaccination is technically harder than inducing systemic antibody responses (like with measles or tetanus).
Animal Model Limitations
- Treponema pallidum cannot be continuously cultured in vitro and has limited animal models.
- gonorrhoea models (mouse, humanized models) imperfectly replicate human infection.
- HSV models are useful but do not always predict human vaccine efficacy.
Ethical & Logistical Barriers in Human Trials
- STI vaccines would need to be evaluated in populations at risk, requiring careful ethical safeguards and long-term follow-up.
- Demonstrating reduced transmission, not just individual protection, requires exceptionally large and costly trials.
Funding and Research Priorities
- Compared to “childhood vaccines” or pandemic pathogens, STIs have historically received less research funding. Only HPV and Hepatitis B vaccines (both STI-related) have succeeded, due to strong cancer-prevention evidence and public-health prioritization. Digital health and prevention innovations
- Digital interventions (reminders, anonymous partner notification apps, AI triage tools) and modelling studies for optimal vaccine deployment add to the public-health toolbox. Long-acting PrEP (cabotegravir) and other sustained-release modalities are reshaping HIV prevention.
Practical recommendations for clinicians and public-health practitioners
- Follow up-to-date national and international treatment guidelines (CDC, WHO) and use local AMR surveillance to guide empiric therapy.
- Prioritize NAATs and extragenital screening for at-risk populations to detect asymptomatic infection.
- Use resistance-guided therapy for MG where testing available; consider referral for culture/susceptibility in persistent or complicated gonorrhoea.
- Implement HPV vaccination programs and integrate PrEP and long-acting prevention where appropriate.
- Engage in stewardship — avoid unnecessary broad antimicrobial use and monitor outcomes when introducing doxy-PEP or novel agents.
Gaps and research priorities
- Accelerate vaccine development for gonorrhea, syphilis and HSV with translational pipelines and human challenge/efficacy trials.
- Scale affordable POC molecular diagnostics and validate self-sampling strategies in diverse settings.
- Monitor and model impacts of doxy-PEP and new antimicrobials on population AMR.
- Improve surveillance systems, particularly for M. genitalium and resistant N. gonorrhoeae, including genomic monitoring.
Conclusion
Management of STIs today combines established antimicrobial regimens with evolving prevention and diagnostic technologies. The most pressing clinical threat is antimicrobial resistance, particularly for gonorrhoea and M. genitalium, but new therapeutics and vaccine research provide realistic pathways to improved control. Implementation of evidence-based screening, vaccination, point-of-care diagnostics, and stewardship strategies alongside equitable access and stigma reduction will be essential to reduce the global STI burden.
Reference
- World Health Organization. Sexually transmitted infections (STIs). WHO Fact Sheet. 2023.
- Unemo M, et al. Global emergence of Neisseria gonorrhoeae resistance. Lancet Infect Dis. 2020;20(7): e82–94.
- Looker KJ, et al. Global estimates of HSV-2 infection. Lancet Infect Dis. 2015;15(8):856–62.
- Global HIV & AIDS statistics — Fact sheet. 2023.
- Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1–187.
- Taylor SN, et al. Zoliflodacin for uncomplicated gonorrhea. N Engl J Med. 2018; 379:1835–45.
