Recent advances in STIs
Dr V Harindra FRCP, FRCP(Glasg) Consultant Physician St. Mary’s Hospital Portsmouth. UK
New cases of STIs diagnosed in GUM clinics -- UK – Improved detection – Changing sexual behaviour • The median age of sexual debut continues to decline • Period of experimentation and changing partners has lengthened • Lack of condom use • Awareness and fear of HIV among MSM & young people have declined
• HPV Vaccine
Health Protection Report Vol 8 No. 24 - 20 June 2014
Early Detection of STIs: The Critical Role of Screening • Most STIs are completely asymptomatic – More than 90% of pharyngeal gonorrhoea in men & women are asymptomatic – Most men (60%) with urethral infection & women (80%) with cervical infection with Chlamydia trachomatis are asymptomatic – 85% of rectal infections with C trachomatis were asymptomatic
Diagnostics • NAAT – – – –
Chlamydia Gonorrhoea Syphilis Other STIs – (TV)
• Multiplex PCR • Point of care test (POCT) • HPV testing
Urine LCR vs EIA Female 2% 27% LCR+ve/ELISA+ve LCR+ve/ELISA -Neg LCR Neg/ELISA +ve
LCR+ve/ELISA+ve LCR+ve/ELISA -Neg LCR Neg/ELISA +ve
562 210 15
71% 27% 2%
LCR+ve/ELISA+ve LCR+ve/ELISA -Neg LCR Neg/ELISA +ve
202 142 8
58% 40% 2%
71%
Male 2% LCR+ve/ELISA+ve
40%
LCR+ve/ELISA -Neg 58%
LCR Neg/ELISA +ve
Point-of-care testing POC technologies Pathogen
Specimen
Antigen
Antibody
Multiplex
HIV
Blood (fingerprick), oral swab
Yes
Yes
Syphilis
Blood (fingerprick)
NA
Yes
HCV
Blood (fingerprick), oral swab
No
Yes
With HIV tests in development
Gonorrhoea
Urethral/vaginal swab
Yes
NA
NAAT with chlamydia
Chlamydia
Urethral/vaginal swab
Yes
NA
NAAT with gonorrhoea
Trichomonas
Vaginal swab
Yes
NA
No
Bacterial vaginosis
Vaginal swab
Enzyme detection
NA
No
Duplex antibody tests with syphilis
• POC test is simple and can provide a rapid result to guide clinical decisions and follow-up during the same encounter
• Improve diagnosis and management of STIs in areas with no or limited access to pathology services • Expand screening, improve syndromic management and reduce loss to follow up • Greater opportunities to offer a full STI screen for people with a positive test • More timely and targeted treatment • Timely and targeted contact tracing Peeling RW Applying new technologies for diagnosing sexually transmitted infections in resource-poor settings. Sex Transm Infect 87 Suppl 2ii28–30
CHLAMYDIA SCREENING Criteria for assessing a screening test Simplicity •
A test should be simple to perform, easy to interpret, & where possible, capable of use by paramedical & other personnel
Acceptability •
A test must be acceptable to those undergoing it
Accuracy •
A test must give a true measurement of the condition or symptoms under investigation
Cost •
The expense of the test must b e considered in relation to the benefits of early detection of disease
Repeatability •
The test should give consistent results in repeated trails
Sensitivity •
The test should be capable of giving a positive finding when the person being screened has the disease being sought
Specificity •
The test should be capable of giving a negative finding when the person being screened does not have the disease being sought
Source: Cochrane & Holland 1971
Modelling Results – 5% and 10% Prevalence
5% Prevalence Screening Rate Optimisation 700
LR rate=HR rate 0% HR Screening Rate 5% 10% 15% 20%
600 550 500 A
450 400
B
C
350 300 0%
1%
2%
3% 4% 5% 6% 7% Low Risk Group Screening Rate
8%
9%
10%
10% Prevalence Screening Rate Optimisation
700 LR rate=HR rate 0% HR Screening Rate 5% 10% 15% 20%
A
650
Cost Estimate - £k
Cost Estimate - £k
650
600 B
550
C
500 450 400 350 300 0%
1%
2%
3% 4% 5% 6% 7% Low Risk Group Screening Rate
8%
9%
10%
Single dose treatment • • • •
Chlamydia Gonorrhoea Syphilis Trichomoniasis
Resistance
Azithromycin Ceftriaxone Benzathine Penicillin Metranidazole
Vaccines • Vaccines for prevention of STIs: HPV, Hepatitis B • Several barriers limit the development of vaccines against sexually transmitted diseases
– The immunity induced by natural infection is absent or imperfect which limits the capacity to define the types of immune responses that an effective vaccine must induce – Reliable animal models are lacking – Goal of these vaccines and definition of endpoints for clinical trials are still unanswered
• Likelihood of success of vaccines against genital herpes, chlamydia, gonorrhoea and trichomonas is uncertain
Vaccine. 2014 Mar 20;32(14):1624-9. doi: 10.1016/j.vaccine.2013.08.032. Epub 2013 Aug 27
HPV Vaccine GARDASIL: HPV vaccine types 6,11,16,18 CERVARIX: directed against HPV 16 and 18 • 3 doses of vaccine – months 0, 2 & 6 – Routine vaccination of females aged 11 or 12 years. The vaccination series can be started beginning at age 9 years – Vaccination is recommended for males aged 11 or 12 years
• May provide some crossover protection for other HPV • Maximum reduction in condyloma risk occurred after 3 doses of quadrivalent HPV vaccine, but 2 doses also considerably reduced condyloma risk • HPV vaccine is not a live vaccine and can be administered to persons who are immunocompromised CDC. FDA licensure of quadrivalent human papillomavirus vaccine (HPV4, Gardasil) for use in males and guidance from the Advisory Committee on Immunization Practices (ACIP). MMWR 2010;59:630–2. JAMA 12/02/14
HSV Prophylactic Vaccines • A prophylactic HSV vaccine that prevents acute disease and establishment of latent infection, holds greatest promise • Two HSV-2 glycoprotein-D-subunit vaccine efficacy trials found – No effect among men or HSV-1 seropositive women – Demonstrated 73–74% efficacy against genital herpes disease among women seronegative for both HSV-1 and HSV-2
• A follow-up trial was conducted among HSV-1 and HSV-2 seronegative women failed to show a vaccine effect on HSV-2 infection & only mildly effective against HSV-1 • The landscape for an effective herpes vaccine is bleak
Curr Opin Infect Dis. 2014;27(1):75-83.
HSV Therapeutic Vaccines • Therapeutic vaccines are another potential strategy for managing patients with existing HSV infection • Many earlier HSV vaccine trials examined effectiveness among individuals with HSV recurrence, although were largely unsuccessful • Therapeutic vaccines aiming to elicit T-cell responses, by using HSV peptides (HerpV) has shown promising results in animal models, humans cells in vitro and Phase I trial • There are forthcoming Phase I/IIa trials designed to examine their safety, immunogenicity and impact on shedding frequency and transmission risk among individuals with genital HSV-2 infection Curr Opin Infect Dis. 2014;27(1):75-83.
Global Resistance of Neisseria gonorrhoeae • Neisseria gonorrhoeae has demonstrated a remarkable genetic capacity to acquire antimicrobial resistance (AMR) • The antimicrobial resistance profile of N. gonorrhoeae is worsening • The most significant recent finding has been the emergence of extensively drug-resistant (XDR) N. gonorrhoeae characterized by very high ceftriaxone minimum inhibitory concentrations • Both ertapenem and solithromycin have good in-vitro activity against resistant N. gonorrhoeae strains • Current strategies to control gonococcal AMR should include, – The use of higher doses of ceftriaxone given as dual therapy with an effective second antimicrobial agent – Azithromycin given in combination with either gentamicin or gemifloxacin has been shown to be an effective alternative antigonococcal therapy
Curr Opin Infect Dis. 2014;27(1):62-67.
Toward global prevention of sexually transmitted infections • Reducing the risk of transmission in any sexual encounter – Condom use – Vaccines – HPV / HepatitisB / ? HSV
• Reducing the rate of sexual partner change – Health promotion
• Reducing the period of infectiousness in individuals
– Population based screening programmes – Targeted screening – Screening and partner notification • Diagnostics - NAAT • Point of care test • Social media
– Simplified therapies to improve compliance • Antimicrobial resistance – New antibiotics
– More accessible services • Primary care
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