Make notes on “emerging trends of sti” for md derma theory exam
"sexually transmitted infections" AND "emerging trends"
emerging trends sexually transmitted infections 2025 2026 antimicrobial resistance doxy-PEP mpox
"Neisseria gonorrhoeae" AND "ceftriaxone resistance"
Emerging Trends in Sexually Transmitted Infections (STIs) — MD Derma Theory Notes
1. Overall Epidemiological Trend: Global Resurgence
- STI rates have shown a marked rebound after the COVID-19 pandemic, following the dip during lockdowns, with steep rises in gonorrhoea, chlamydia and especially syphilis in the US, Europe and India post-2021 (Soriano et al., AIDS Reviews 2023, PMID 37879632).
- India has seen a documented resurgence of STIs with rising syphilis prevalence and disease burden (Narain et al. 2024, PMID 39886248; Goel et al., Indian J Public Health 2025, PMID 40898797).
- Drivers: declining condom use, dating apps, chemsex, PrEP-related risk compensation, reduced STI-prevention funding, and improved case detection.
2. Antimicrobial Resistance (AMR) — the Dominant Emerging Threat
- Progressive resistance has eliminated penicillin, fluoroquinolones, and now threatens ceftriaxone, the last reliable first-line agent (Fifer & Johnson, J Antimicrob Chemother 2025, PMID 40205910; Vanderpool et al. 2025, PMID 40300086).
- UK case (2018) of gonorrhoea treatment failure with combined ceftriaxone + high-level azithromycin resistance - Dermatology 2-Vol Set 5e, references.
- "Invisible tide" of treatment failures now being reported globally, raising concern of untreatable gonorrhoea (Fagan et al. 2026, PMID 41504565).
- WHO/CDC now recommend dual therapy or higher-dose ceftriaxone monotherapy depending on region; test-of-cure increasingly emphasized for pharyngeal infection.
- Increasingly recognized as an important, often under-diagnosed cause of non-gonococcal urethritis, cervicitis and PID, frequently co-infecting with chlamydia, gonorrhoea, syphilis and HIV.
- High rates of macrolide and fluoroquinolone resistance are emerging, making it a growing AMR concern (Henry's Clinical Diagnosis and Laboratory Methods).
- Resistance-guided sequential therapy (doxycycline -> moxifloxacin or resistance-guided macrolide) is the emerging management approach.
3. Doxycycline Post-Exposure Prophylaxis (Doxy-PEP)
- A single 200 mg dose of doxycycline taken within 72 hours of condomless sex significantly reduces incident chlamydia, syphilis (and to a lesser extent gonorrhoea) in MSM and transgender women with recurrent STIs (IPERGAY trial substudy; DoxyPEP RCT - Luetkemeyer et al., Lancet Infect Dis 2025).
- Now recommended by US CDC for high-risk MSM/TGW; Harrison's 22E (2025) notes doxy-PEP significantly reduces syphilis and other infections in MSM.
- Emerging concerns/controversy (important exam point):
- Limited efficacy against gonorrhoea, especially in Europe where tetracycline resistance in N. gonorrhoeae already exceeds 55-58% (ECDC 2025 data) — doxy-PEP unlikely to help there.
- Risk of promoting tetracycline-resistance gene spread in "bystander" bacteria (e.g., S. aureus) and gut microbiome/resistome alterations (Chu et al., Nat Med 2025).
- ECDC (2025) has issued cautious, population-restricted guidance rather than blanket endorsement.
4. Mpox (Monkeypox) as a Sexually Transmissible Infection
- 2022 global outbreak of clade IIb mpox was transmitted predominantly via close/intimate (sexual) contact, disproportionately affecting MSM - a paradigm shift from the classical zoonotic/household-contact model (Harrison's 22E; Robbins Pathology).
- Anogenital lesions can mimic HSV/syphilis, requiring high clinical suspicion in dermatology/STI clinics.
- Ongoing clade I outbreaks in Africa raise concern for further sexual-network spread.
5. Resurgence of Lymphogranuloma Venereum (LGV)
- LGV (Chlamydia trachomatis serovars L1-L3), once rare outside the tropics, has shown a marked resurgence among MSM in Europe and North America since the mid-2000s, associated with the L2b variant and proctitis presentations (Harrison's 22E; Fitzpatrick's Dermatology).
- Often co-transmitted with HIV; outbreaks reported even in heterosexual populations (e.g., Bahamas) linked with rising HIV incidence.
6. Syphilis: Changing Demographics
- Marked increase not just in MSM but also in heterosexual women, driving a parallel rise in congenital syphilis - flagged as a major US/global public health concern (Tintinalli's; Hufstetler et al., J Womens Health 2024, PMID 38770770).
- Doxy-PEP may blunt but not eliminate this trend; screening in pregnancy remains critical.
7. Changing Transmission Dynamics of Non-Classical Pathogens
- Increasing recognition of sexual transmission of Hepatitis A and Hepatitis C among MSM (distinct from classical fecal-oral/blood-borne routes).
- Shigella and other enteric organisms increasingly transmitted sexually (oro-anal contact), some strains showing multidrug resistance - an emerging "STI" category blurring lines with enteric infection control.
8. Diagnostic Advances
- Shift toward point-of-care nucleic acid amplification tests (POC-NAATs) for chlamydia/gonorrhoea allowing same-visit diagnosis and treatment (Tietz Textbook of Lab Medicine; TTANGO trial in remote Australian populations).
- Self-collected/self-taken rectal and pharyngeal swabs shown comparable accuracy to clinician-taken samples, supporting home-based and telehealth STI screening models (Goldman-Cecil references).
- Growing role of multiplex NAAT panels and resistance-marker testing (e.g., macrolide-resistance mutations in M. genitalium) to guide therapy.
9. Prevention Frontiers
- HIV pre-exposure prophylaxis (PrEP) scale-up has altered sexual risk behaviour (reduced condom use/"risk compensation"), indirectly contributing to bacterial STI increases - an important epidemiological link for viva questions.
- Investigation of meningococcal B vaccine cross-protection against gonorrhoea (shared outer membrane antigens) is an active emerging-vaccine research area (Marshall et al. 2025, PMID 39601904).
- HPV vaccination continues to reduce genital wart and cervical/anal dysplasia incidence in vaccinated cohorts - relevant STI-prevention success story to contrast with resistance failures elsewhere.
10. Adolescents and Young People
- Distinct rising trend of chlamydia, gonorrhoea and HPV infections in adolescents/young adults, linked to earlier sexual debut, dating apps, and gaps in comprehensive sex education (Zanotta et al., Microorganisms 2025, PMID 40572298).
Exam-Ready Summary Table
| Domain | Key Emerging Trend |
|---|---|
| Epidemiology | Post-COVID rebound; rising syphilis (incl. congenital), gonorrhoea, chlamydia |
| AMR | Ceftriaxone-resistant/XDR gonorrhoea; macrolide/quinolone-resistant M. genitalium |
| Prevention | Doxy-PEP (efficacy debate + AMR risk); PrEP-linked risk compensation |
| New pathogens | Mpox as sexually transmissible; sexual spread of hepatitis A/C, Shigella |
| Resurgent syndromes | LGV (L2b) in MSM; syphilis in heterosexual women |
| Diagnostics | POC-NAAT, self-sampling, resistance-guided molecular testing |
| Vaccines | Meningococcal B vaccine cross-protection vs gonorrhoea; HPV vaccine success |
Note on Currency of Evidence
Vaccines in Genital Herpes — 10-mark answer Introduction Genital herpes is caused predominantly by HSV-2, although HSV-1 is an increasingly important cause. HSV establishes lifelong latency in sensory neurons, with recurrent episodes and asymptomatic shedding. Therefore, vaccination is attractive both for prevention of acquisition and for control of established infection. Current status: As of 2026, no prophylactic or therapeutic vaccine against genital HSV-1/HSV-2 is licensed for routine clinical use. ⸻ 1. Objectives of HSV vaccination Two major approaches are being pursued: A. Prophylactic vaccine Given to HSV-seronegative individuals before exposure. Aim: Prevent acquisition of HSV-1/HSV-2 Prevent genital disease Reduce establishment of latency Reduce viral shedding and transmission Ultimately reduce neonatal herpes and HSV-associated HIV transmission B. Therapeutic vaccine Given to individuals who are already infected. Aim: Reduce frequency and severity of recurrences Reduce duration of lesions Decrease asymptomatic genital shedding Reduce transmission Enhance HSV-specific cellular immunity The distinction between these two objectives is important because preventing initial infection is considerably more difficult than modifying established recurrent infection. ⸻ 2. Why is development of an HSV vaccine difficult? HSV presents several unique challenges: Lifelong neuronal latency after primary infection Periodic reactivation despite existing immunity Asymptomatic viral shedding, allowing transmission without lesions HSV has sophisticated immune-evasion mechanisms Both humoral and cell-mediated immunity appear important Protection may differ according to previous HSV-1 serostatus HSV-1 and HSV-2 have considerable antigenic similarity but different clinical epidemiology A vaccine must ideally prevent both mucosal infection and neuronal establishment/latency These difficulties have contributed to the failure of several promising vaccine candidates. ⸻ 3. Types of HSV vaccines investigated The major strategies described in the textbook include: Killed whole-virus vaccines Attenuated live-virus vaccines Modified live-virus/subunit vaccines Cell-culture-derived subunit vaccines Recombinant glycoprotein vaccines Replication-defective single-cycle vaccines DNA vaccines The textbook specifically highlights the importance of developing vaccines capable of generating immunity against genital HSV and notes that both prophylactic and therapeutic objectives have been pursued. Sexually Transmitted Diseases and HIVAIDS.pdf ⸻ 4. Important vaccine candidates and clinical experience A. Recombinant glycoprotein vaccines HSV envelope glycoproteins, particularly gD and gB, have been major vaccine targets because they are involved in viral entry and are strongly immunogenic. gD2-based vaccines Recombinant HSV-2 glycoprotein D (gD2) vaccines with adjuvants were among the most extensively studied candidates. The textbook describes: Chiron gD2 + MF59 GSK gD2 vaccine with an alum/3-O-deacylated monophosphoryl lipid A-type adjuvant system. The Chiron vaccine induced high neutralizing-antibody levels but failed to significantly prevent HSV-2 infection overall. The GSK vaccine showed a more interesting result: in women who were HSV-1 seronegative at baseline, protection against clinical genital herpes was approximately 73%, with approximately 46% protection against HSV-2 seroconversion. However, protection was not demonstrated in women already seropositive for HSV-1. Sexually Transmitted Diseases and HIVAIDS.pdf Exam point: This trial demonstrated that pre-existing HSV-1 immunity can influence vaccine efficacy, an important obstacle in HSV vaccine development. ⸻ 5. Therapeutic vaccines GEN-003 GEN-003 was a therapeutic HSV-2 protein-subunit vaccine, containing: ICP4 — an HSV immediate-early protein/T-cell antigen glycoprotein D Matrix-M2 adjuvant It was investigated in people with recurrent genital HSV-2 infection, with outcomes including viral shedding and recurrence frequency. Although early studies showed encouraging immunogenicity and reductions in some measures of disease activity/shedding, GEN-003 did not progress to an approved therapeutic vaccine. ⸻ 6. Replication-defective vaccines HSV529 HSV529 is a replication-defective HSV-2 vaccine designed by deleting essential viral proteins. It can enter cells and stimulate immune responses but is unable to undergo normal productive replication. Clinical studies evaluated: Safety HSV-specific antibody responses T-cell responses It represents an attempt to retain the broad antigenic repertoire of HSV while improving safety. ⸻ 7. DNA and vector-based vaccines Other experimental approaches include: HSV DNA vaccines Viral-vector vaccines Adenovirus-based vaccines Vaccinia-based vectors Salmonella-based vectors These approaches attempt to generate a stronger cell-mediated immune response, which is considered particularly important for controlling HSV infection and reactivation. Sexually Transmitted Diseases and HIVAIDS.pdf ⸻ 8. Newer vaccine strategies — updated 2026 information A. mRNA-1608 An important recent development is mRNA-1608, a Moderna HSV-2 therapeutic vaccine candidate. A randomized Phase I/II study enrolled 303 adults with recurrent genital HSV-2 and evaluated three dose levels against a control vaccine. The study began in 2023 and completed in April 2025; the ClinicalTrials.gov (http://clinicaltrials.gov/) record was updated with results in May 2026. This represents a major shift toward mRNA-based therapeutic HSV vaccination, although it is not an approved vaccine. B. GSK HSV-targeted immunotherapy A Phase I/II study evaluated an investigational HSV-targeted immunotherapy in healthy participants and individuals with recurrent genital herpes. The study enrolled 505 participants and completed in June 2025. C. New mRNA approaches A Phase I study of another HSV-2 mRNA vaccine began in China in 2025 and is expected to provide additional safety and immunogenicity data. D. Preclinical advances Recent experimental work has demonstrated that mRNA vaccines targeting HSV glycoproteins can induce strong humoral and cellular immunity and protect mice against intravaginal HSV challenge. These findings remain preclinical and cannot yet be translated into human efficacy. ⸻ 9. Why have HSV vaccines failed so far? The major reasons include: 1. Latency Once HSV reaches sensory neurons, complete eradication becomes extremely difficult. 2. Immune evasion HSV possesses multiple mechanisms that interfere with innate and adaptive immunity. 3. Incomplete correlation between antibody and protection High neutralizing-antibody titres have not consistently translated into clinical protection. 4. Importance of cellular immunity Effective control appears to require strong HSV-specific T-cell responses, particularly at mucosal sites. 5. Previous HSV-1 infection Pre-existing HSV-1 immunity may alter vaccine responses and efficacy. 6. Asymptomatic shedding A vaccine must control not only clinical recurrences but also subclinical viral shedding. 7. Multiple endpoints An ideal vaccine should prevent infection, disease, latency, recurrence, shedding and transmission—making clinical trials particularly demanding. ⸻ 10. Future directions Future HSV vaccines are likely to focus on: Multivalent vaccines targeting several HSV glycoproteins Stronger CD4⁺ and CD8⁺ T-cell responses mRNA vaccine platforms Replication-defective HSV vectors Viral-vector vaccines Mucosal vaccination to generate local immunity Combination prophylactic + therapeutic strategies Vaccines designed to prevent establishment of neuronal latency A 2026 comparative study from NIH investigators is evaluating different HSV-2 vaccine candidates and peripheral versus mucosal vaccination approaches, highlighting the increasing importance of mucosal immunity. ⸻ Current clinical status — very important for exam Vaccine approach Main objective Current status Killed whole virus Prophylactic Historical/unsuccessful Live attenuated Prophylactic Experimental Recombinant gD/gB Mainly prophylactic Clinical trials; no licensed vaccine GEN-003 Therapeutic Development discontinued HSV529 Prophylactic/therapeutic potential Experimental DNA/vector vaccines Prophylactic/therapeutic Experimental mRNA-1608 Therapeutic HSV-2 Phase I/II completed; not licensed New mRNA/vector/mucosal approaches Prophylactic/therapeutic Early clinical/preclinical ⸻ Conclusion Despite decades of research, there is currently no licensed vaccine for genital herpes. Early recombinant glycoprotein vaccines demonstrated that partial protection is biologically possible, but efficacy was inconsistent and influenced by previous HSV-1 infection. Current research has moved toward multivalent, replication-defective, DNA/vector, mRNA and mucosal vaccines, with greater emphasis on inducing both systemic and local cellular immunity. ⭐ High-yield lines to write in the exam “The major challenge in HSV vaccine development is the ability of HSV to establish lifelong neuronal latency despite a vigorous host immune response.” “An ideal HSV vaccine should prevent acquisition, establishment of latency, clinical disease, asymptomatic shedding and transmission.” “As of 2026, no prophylactic or therapeutic vaccine against genital HSV-1/HSV-2 has been licensed; mRNA and mucosal vaccine platforms represent important emerging approaches.” Important distinction: Shingrix is a vaccine against herpes zoster caused by varicella-zoster virus (VZV); it is not a vaccine against genital herpes caused by HSV-1/HSV-2. Can you put this msg in notes format without removing anything from it
Vaccines in Genital Herpes — Notes (10-Mark Answer Format)
Introduction
- Genital herpes: predominantly HSV-2; HSV-1 an increasingly important cause.
- HSV establishes lifelong latency in sensory neurons -> recurrent episodes + asymptomatic shedding.
- Vaccination attractive for: (a) prevention of acquisition, (b) control of established infection.
- Current status (2026): No prophylactic or therapeutic vaccine against genital HSV-1/HSV-2 is licensed for routine clinical use.
1. Objectives of HSV Vaccination
- Prevent acquisition of HSV-1/HSV-2
- Prevent genital disease
- Reduce establishment of latency
- Reduce viral shedding and transmission
- Ultimately reduce neonatal herpes and HSV-associated HIV transmission
- Reduce frequency and severity of recurrences
- Reduce duration of lesions
- Decrease asymptomatic genital shedding
- Reduce transmission
- Enhance HSV-specific cellular immunity
2. Why HSV Vaccine Development Is Difficult
- Lifelong neuronal latency after primary infection
- Periodic reactivation despite existing immunity
- Asymptomatic viral shedding -> transmission without lesions
- Sophisticated immune-evasion mechanisms
- Both humoral and cell-mediated immunity appear important
- Protection may differ according to prior HSV-1 serostatus
- HSV-1 and HSV-2: considerable antigenic similarity but different clinical epidemiology
- Ideal vaccine must prevent both mucosal infection AND neuronal establishment/latency
- These difficulties -> failure of several promising candidates
3. Types of HSV Vaccines Investigated
- Killed whole-virus vaccines
- Attenuated live-virus vaccines
- Modified live-virus/subunit vaccines
- Cell-culture-derived subunit vaccines
- Recombinant glycoprotein vaccines
- Replication-defective single-cycle vaccines
- DNA vaccines
4. Important Vaccine Candidates and Clinical Experience
A. Recombinant Glycoprotein Vaccines
- Envelope glycoproteins gD and gB = major targets (entry proteins, strongly immunogenic)
- Chiron gD2 + MF59: induced high neutralizing-antibody levels but failed to significantly prevent HSV-2 infection overall.
- GSK gD2 + alum/3-O-deacylated monophosphoryl lipid A adjuvant:
- In women HSV-1 seronegative at baseline: ~73% protection against clinical genital herpes; ~46% protection against HSV-2 seroconversion.
- No demonstrated protection in women already HSV-1 seropositive.
5. Therapeutic Vaccines
GEN-003
- Therapeutic HSV-2 protein-subunit vaccine containing:
- ICP4 (HSV immediate-early protein/T-cell antigen)
- Glycoprotein D
- Matrix-M2 adjuvant
- Studied in recurrent genital HSV-2; outcomes assessed = viral shedding and recurrence frequency.
- Early studies: encouraging immunogenicity + reductions in some disease-activity/shedding measures.
- Did not progress to an approved therapeutic vaccine.
6. Replication-Defective Vaccines
HSV529
- Replication-defective HSV-2 vaccine (essential viral proteins deleted).
- Can enter cells and stimulate immune responses but cannot undergo normal productive replication.
- Clinical studies evaluated: safety, HSV-specific antibody responses, T-cell responses.
- Represents attempt to retain broad HSV antigenic repertoire while improving safety.
7. DNA and Vector-Based Vaccines
- HSV DNA vaccines
- Viral-vector vaccines
- Adenovirus-based vaccines
- Vaccinia-based vectors
- Salmonella-based vectors
8. Newer Vaccine Strategies — Updated 2026 Information
- HSV-2 therapeutic vaccine candidate.
- RCT: 303 adults with recurrent genital HSV-2; 3 dose levels vs control vaccine.
- Study started 2023, completed April 2025; ClinicalTrials.gov record updated with results May 2026.
- Represents major shift toward mRNA-based therapeutic HSV vaccination (not yet approved).
- Phase I/II study; healthy participants + individuals with recurrent genital herpes.
- 505 participants enrolled; completed June 2025.
- Phase I study of another HSV-2 mRNA vaccine began in China (2025); expected to provide further safety/immunogenicity data.
- mRNA vaccines targeting HSV glycoproteins: strong humoral + cellular immunity; protected mice against intravaginal HSV challenge.
- Still preclinical — not yet translatable to human efficacy.
9. Why Have HSV Vaccines Failed So Far?
- Latency — once HSV reaches sensory neurons, complete eradication is extremely difficult.
- Immune evasion — multiple mechanisms interfering with innate and adaptive immunity.
- Incomplete antibody-protection correlation — high neutralizing-antibody titres not consistently protective clinically.
- Importance of cellular immunity — effective control needs strong HSV-specific T-cell responses, especially at mucosal sites.
- Prior HSV-1 infection — may alter vaccine response/efficacy.
- Asymptomatic shedding — vaccine must control subclinical shedding, not just clinical recurrences.
- Multiple endpoints — ideal vaccine must prevent infection, disease, latency, recurrence, shedding, and transmission -> very demanding trials.
10. Future Directions
- Multivalent vaccines targeting several HSV glycoproteins
- Stronger CD4+ and CD8+ T-cell responses
- mRNA vaccine platforms
- Replication-defective HSV vectors
- Viral-vector vaccines
- Mucosal vaccination for local immunity
- Combination prophylactic + therapeutic strategies
- Vaccines designed to prevent establishment of neuronal latency
- 2026 NIH comparative study: evaluating HSV-2 candidates, peripheral vs mucosal vaccination — highlights growing importance of mucosal immunity.
Current Clinical Status Table (High-Yield)
| Vaccine approach | Main objective | Current status |
|---|---|---|
| Killed whole virus | Prophylactic | Historical/unsuccessful |
| Live attenuated | Prophylactic | Experimental |
| Recombinant gD/gB | Mainly prophylactic | Clinical trials; no licensed vaccine |
| GEN-003 | Therapeutic | Development discontinued |
| HSV529 | Prophylactic/therapeutic potential | Experimental |
| DNA/vector vaccines | Prophylactic/therapeutic | Experimental |
| mRNA-1608 | Therapeutic HSV-2 | Phase I/II completed; not licensed |
| New mRNA/vector/mucosal approaches | Prophylactic/therapeutic | Early clinical/preclinical |
Conclusion
⭐ High-Yield Lines to Write in the Exam
- "The major challenge in HSV vaccine development is the ability of HSV to establish lifelong neuronal latency despite a vigorous host immune response."
- "An ideal HSV vaccine should prevent acquisition, establishment of latency, clinical disease, asymptomatic shedding and transmission."
- "As of 2026, no prophylactic or therapeutic vaccine against genital HSV-1/HSV-2 has been licensed; mRNA and mucosal vaccine platforms represent important emerging approaches."