Winston Tilghman, MD Medical Director, STD Controller HIV, STD & Hepatitis Branch of Public Health Services County of San Diego Health & Human Services Agency

1. HIV & Global Health Rounds
The UC San Diego AntiViral Research Center sponsors weekly
presentations by infectious disease and global public health clinicians,
physicians, and researchers. The goal of these presentations is to
provide the most current research, clinical practices, and trends in HIV,
HBV, HCV, TB, and other infectious diseases of global significance.
The slides from the HIV & Global Health Rounds presentation that you
are about to view are intended for the educational purposes of our
audience. They may not be used for other purposes without the
presenter’s express permission.

2. SEXUALLY TRANSMITTED
INFECTIONS – 2020 UPDATE
M. Winston Tilghman, MD
Medical Director, HIV, STD, & Hepatitis Branch
Division of Public Health Services
UCSD HIV & Global Health Rounds – August 21, 2020
PUBLIC HEALTH SERVICES

3. FACULTY DISCLOSURES
 None

4. LEARNING OBJECTIVES
 After attending this presentation, learners should be able
to:
 Describe the local epidemiology of bacterial sexually transmitted
infections (STIs)
 Diagnose and treat syphilis, gonorrhea, chlamydia, and
Mycoplasma genitalium infections
 Discuss anticipated changes in STI treatment recommendations

5. Interim Guidance during COVID-19
COMING SOON:
2020 STD Treatment
Guidelines
STD RESOURCES (CDC)

6. Syphilis

7. NATURAL HISTORY OF
UNTREATED SYPHILIS

8. PRIMARY SYPHILIS
 10-90 days after exposure
 Chancre:
 Painless indurated ulcer
 Occurs at site of
inoculation
 Lymphadenopathy may be
present:
 Painless, rubbery
 Inguinal or femoral
 May go unnoticed Photo Credit:
CDC

9. PRIMARY SYPHILIS
 Among 183 men with T. pallidum PCR-confirmed anogenital primary lesions:
 Painful lesions in 49.2%, multiple lesions in 37.7%
 Both painful and multiple lesions in 20.2% (8% had + HSV PCR)
 HIV+ men more likely to have anal lesions than HIV-; o/w no difference from HIV-
Towns et al, STI 2016

10. SECONDARY SYPHILIS
 3-6 weeks after primary chancre
 Systemic infection following hematogenous
dissemination
 Constitutional symptoms in 50-80%
 Generalized lymphadenopathy (70-90%)
 Rash in 75-90%
 Palmar/plantar in 60%
 Condylomata lata (5-25%)
 Mucous patches (5-30%)
 Patchy alopecia (10-15%)
 Less common: meningitis, hepatitis, nephritis, arthritis

11. SECONDARY SYPHILIS - RASH
Photo Credit:
Photo Credits: Gregory Melcher, UC Davis, Susan
Philip, SF DPH & UCSF

12. SECONDARY SYPHILIS –
OTHER MANIFESTATIONS
Courtesy: Gregory Melcher, UC Davis, Susan Philip, SF DPH
& UCSF

13. NEUROSYPHILIS
 Asymptomatic CNS invasion
 Symptomatic syphilitic meningitis (often with cranial nerve
involvement)
 Asymptomatic meningitis
 Meningovascular events
 General paresis
 Tabes dorsalis
 Ocular syphilis
 Otic syphilis
• Screen all patients with syphilis
for neurological, ocular and otic
symptoms, and perform
neurological exam.

14. OCULAR SYPHILIS
Manifestations:
• Conjunctivitis, scleritis, and episcleritis
• Uveitis: anterior and/or posterior
• Elevated intraocular pressure
• Chorioretinitis, retinitis
• Vasculitis
Symptoms:
• Redness
• Eye pain
• Floaters
• Flashing lights
• Visual acuity loss
• Blindness
Diagnosis:
• Ophthalmologic exam
• Serologies: RPR, VDRL, treponemal tests
• Lumbar puncture
Wender, JD et al. How to Recognize Ocular Syphilis. Review of Ophthalmology. 2008
Slide courtesy of Sarah Lewis, MD

15. OCULAR SYPHILIS
• Review of cases of syphilis from 2014-2015
with ocular manifestations in eight
jurisdictions (CA, FL, IN, MD, NYC, NC, TX,
WA)
• Ocular in 0.53% (2014) and 0.63% (2015) of

16. OCULAR SYPHILIS
 Initial reports from WA included two sex partners
(Woolston et al, MMWR 2015).
 None of the ocular syphilis cases from FL, IN, NC, and
NYC named sexual partners with ocular syphilis (Oliver
et al, MMWR 2016).
 No specific strain was identified in patients with ocular
syphilis on molecular analysis (Oliver et al, STD 2016).

17. TERTIARY SYPHILIS
 Gummas: granulomas of skin,
bones, viscera
 Neuro: General paresis and
tabes dorsalis are considered
"tertiary" forms of neurosyphilis
 Cardiovascular – aortitis 
dilated aorta  aortic
regurgitation

18. CONGENITAL SYPHILIS
 In utero transmission of T. pallidum
 Can occur with any stage of maternal syphilis
 Can cause multiple complications during pregnancy and after delivery,
including fetal demise
 2/3 asymptomatic at birth
 Complications can occur during puberty/adolescence, may be
permanent.
 Screen all pregnant women for syphilis at first prenatal visit and, if at
high risk, at 28-32 weeks’ gestation and at delivery
 CDC-recommended penicillin-based Tx for pregnant women
 PCN allergy  desensitization

19. 48 38 46
72
152
220
314
364
515
519
399
456 454
578 576
668
829
981
1130
1079
0.9 1.0 0.9 1.3
3.7
4.6
6.3
7.6
11.2 11.0
8.6
14.7 14.5
18.3 18.0
20.7
25.4
29.8
34.1
32.3
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
0
200
400
600
800
1000
1200
Rateper100,000Population
NumberofCases
Year
Cases Rate per 100,000 population
Early Syphilis Cases and Rates by Year
San Diego County, 1999 - 2018

20. 12 13 14
39 127 161 204 284 401 398 314 383 358 468 477 527 723 841 966 890
48 38 46
72
152
220
314
364
515 519
399
456 454
578 576
668
829
981
1130
1079
0
200
400
600
800
1000
1200
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
NumberofCases
Year
Men who have sex with men Other
Early Syphilis Cases by Year
San Diego County, 1999 - 2018

21. 3.6*
60.7
0.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
Rateper100,000Population
Year
Females Males
* Between 2017 and 2018 the female early syphilis rate increased by 24% and the number of cases increased by 25%.
Early Syphilis Rates by Gender and Year
San Diego County, 2010 - 2018

22. STD Control Branch
22
Congenital Syphilis Cases versus Females of Childbearing
Age (15-44) Early Syphilis* Cases by Pregnancy Status
California, 2009–2018
* Includes primary, secondary, and early non-primary non-secondary syphilis.
Rev. 7/2019

23. 0.0 0.0 0.9
5.2 5.9
3.6 5.1
0.60.0 0.0
13.3
54.2
93.0
68.8
45.6
21.4
0
10
20
30
40
50
60
70
80
90
100
<10 10-14 15-19 20-24 25-29 30-34 35-44 45+
Rateper100,000Population
Age Group
Female Male
Rates calculated using 2018 population estimates provided by the Community Health Statistics Unit.
Primary & Secondary Syphilis Rates
by Gender and Age
San Diego County, 2018

24. 0.0 0.5
2.9 1.9 2.2
51.5
24.6
77.4
32.9
23.5
0
10
20
30
40
50
60
70
80
90
Native American/
Alaskan Native
Asian/Pacific
Islander
Black Hispanic White
Rateper100,000Population
Race/Ethnicity
Female Male
Note: Rates exclude 16 cases missing race/ethnicity information and 19 cases with other/mixed race designations .
Rates calculated using 2018 population estimates provided by the Community Health Statistics Unit.
Primary & Secondary Syphilis Rates
by Gender and Race/Ethnicity
San Diego County, 2018

25. SYPHILIS DIAGNOSIS –
SEROLOGIC TESTING
Non-Treponemal Tests Treponemal Tests
Detect antibodies to mammalian cell
components (e.g., cardiolipin, lecithin)
Detect antibodies to T. pallidum surface
proteins
Non-specific – false-positive results
occur (e.g., autoimmune diseases)
Specific
Semiquantitative (if reactive): result
given as titer (e.g., 1:1, 1:2, 1:4, 1:8)
Qualitative
Correlate with disease activity Positive for life in most after initial
infection (required for initial Dx)
Negative in ~25% with early primary
syphilis
Negative in ~10% with early primary
syphilis
Examples: RPR, VDRL, TRUST Examples: TPPA, MHA-TP, FTA-ABS,
EIAs, CIAs
2015 STD Treatment Guidelines

26. SEROLOGIC TESTING ALGORITHMS

27. SEROLOGIC TEST
CHARACTERISTICS
 RPR sensitivity:
 Primary: 62-78%, Secondary 97-100%, Early latent 82-100%, Tertiary 47-64%
 Prozone effect can result in false-negative RPR (usually during secondary syphilis).
Park et al, CID 2019

28. SYPHILIS DIAGNOSIS –
DIRECT TESTING
DARKFIELD MICROSCOPY (DFM)
 Point-of-care test due to strict specimen stability
requirements
 Should be viewed within 20 minutes of specimen
collection to minimize loss of motility
 Should not be performed on oral lesions
 T. denticola is indistinguishable morphologically from
T. pallidum
 Technical expertise required:
 Differentiate from other spirochetes that are normal
flora (e.g., T. refringens in genital region)
CDC/ Richard O. Deitrick
Theel et al, CID 2020

29. SYPHILIS DIAGNOSIS –
DIRECT TESTING
OTHER METHODS
Theel et al, CID 2020
 Direct fluorescence antibody (DFA) testing:
 Can be performed on lesions and fluids (e.g., CSF, AF)
 Specimen applied and ethanol fixed to slide, stained with fluorescent mono- or
polyclonal antibodies
 None are FDA-approved
 Easier to interpret than DFM, does not require immediate evaluation
 H9-1 monoclonal antibody – specific to T. pallidum subsp. pallidum and pertenue
 Can be performed on anogenital and oral lesions with low false-positives
 Silver stains and immunohistochemistry (IHC) – on tissue sections

30. SYPHILIS DIAGNOSIS –
DIRECT TESTING
Theel et al, CID 2020

31. SYPHILIS DIAGNOSIS –
DIRECT TESTING
NUCLEIC ACID AMPLIFICATION TESTING (NAAT)
Theel et al, CID 2020
 Variety of assays have been developed
 None are commercially available, to date.
 Assays involving two targets have been the most
studied:
 T. pallidum 47kDa lipoprotein (tpp47)
 DNA polymerase I gene (polA)

32. SYPHILIS DIAGNOSIS –
DIRECT TESTING (NAAT)
Theel et al, CID 2020

33. DIRECT MOLECULAR
TESTING CHALLENGES
 Low and transient bacterial burden in accessible anatomic sites
 Ability of T. pallidum to persist in CNS
 Historical lack of in vitro culture system to provide ample material for
test evaluation
 Lack of a clear gold standard:
 Recent studies suggest that rabbit infectivity test (RIT) has
sensitivity of <50% (Tong et al, Clin Chim Acta 2017)
Kersch and Workowski, CID 2020

34. SYPHILIS DIAGNOSIS -
NEUROSYPHILIS
 Neurosyphilis:
 CSF examination for cell count, protein, VDRL (insensitive but highly
specific), FTA-ABS can be helpful (highly sensitive but less specific))
 Indicated for patients with signs or symptoms, treatment failure, signs
of tertiary syphilis (cardiovascular, gummas)
 Ocular syphilis:
 Ophthalmologic exam
 CSF examination (as for neurosyphilis)
 Otic syphilis:
 Clinical diagnosis but audiology exam, CSF exam should be done
If patient has ocular syphilis or
otosyphilis, treat as neurosyphilis,
regardless of CSF profile.
2015 STD Treatment Guidelines

35. SYPHILIS STAGING
Sign/Symptoms No Signs/Symptoms
*Primary (chancre)
*Early Latent (if meets any of the
following within <1 year):
• Negative syphilis serology
• Known contact to early case
• Good history of typical signs/Sx
• 4-fold increase in non-
treponemal titer
• Only possible exposure
*Secondary (rash, condylomata lata,
mucous patches, etc.)
Late Latent or Unknown Duration (≥1
year or unknown)
Tertiary (gummas, aortitis)
Neurosyphilis (early or late, includes
ocular and otic syphilis)
• *Sexual transmission is possible during these stages.
• High RPR titer & lack of previous history are not criteria for early syphilis.
2015 STD Treatment Guidelines

36. SYPHILIS TREATMENT
Stage(s) Recommended Tx
Primary, Secondary, Early Latent
Long-acting benzathine penicillin G 2.4 million
units IM once
Alt*: doxycycline 100 mg p.o. BID x 14 days, CTX
Late Latent or Unknown Duration, Tertiary
Syphilis (without neurosyphilis)
Long-acting benzathine penicillin G 2.4 million
units IM weekly x 3 (total 7.2 million units)
Alt*: doxycycline 100 mg p.o. BID x 28 days, CTX
Neurosyphilis (early or late, includes ocular
and otic syphilis)
Aqueous crystalline penicillin G 18-24 million
units IV daily x 10-14 days
Alt: IM procaine PCN + oral probenecid, CTX
2015 STD Treatment Guidelines
• Additional antibiotics/doses have not been shown to be
effective.
• For neuro, ocular, & otic syphilis diagnosed in setting of late
syphilis (or unknown duration), 1-3 weekly IM BPG injections
recommended after completion of IV Tx.
• Always order RPR titer on day of treatment initiation.
• 2020 STD Treatment Guidelines: no major changes* For non-pregnant adults

37. SYPHILIS FOLLOW-UP
 Serologic treatment nonresponse = failure to achieve at least a fourfold (two-dilution)
decline in nontreponemal test titer:
 Early: 6-12 months
 Late/unknown: 12-24 months
 Nontreponemal test titers may decline more slowly for persons previously treated for
syphilis.
 Serologic response is associated with several factors:
 Stage of syphilis
 Initial nontreponemal titers
 Age (older patients less likely to decline fourfold)

38. Gonorrhea

39. GONORRHEA CLINICAL MANIFESTATIONS
 Urethritis
 Epididymitis
 Cervicitis
 Salpingitis/PID
 Pharyngitis (or asymptomatic)
 Proctitis (or asymptomatic)
 Conjunctivitis
 Disseminated infection
 Infants: pharyngitis or asymptomatic, ophthalmia
neonatorum
Photo Credits: 1) STD Atlas, 1997 2) Mosby 3) CDC

40. DISSEMINATED GONOCOCCAL
INFECTION (DGI)
 Dermatitis-arthritis
syndrome
 Tenosynovitis
 Dermatitis
 Polyarthralgia
 Septic arthritis (30-40%)
 Wrists, MCPs, knees,
ankles most common
 Endocarditis, meningitis,
perihepatitis (rare)
Photo Credit: CDC

41. DISSEMINATED GONOCOCCAL
INFECTION (DGI)
 Probably underreported
 In December 2019, CDC alerted public health officials of increasing reports
of DGI and a cluster of DGI cases in Michigan (n=17)
 Mostly MSW (9) and WSM (6)
 Associated with methamphetamine use (n=10) and some opiate (3) use
 Clinical manifestations: septic arthritis (13), tenosynovitis (3), myositis
(4), osteomyelitis (2), endocarditis (1)
 15 hospitalized, 14 required surgical intervention, all survived
 Of 12 isolates available for AST, all susceptible to first-line agents
 Isolates from DGI cases should be sent to CDC for analysis.

42. 1560
17971875
2128
1972
2376
2606
2767
2385
2016
1843
2019
2166
2597
2865
3391
3695
4992
5947
6200
56.7
63.9 65.5
72.9
66.4
78.9
85.7
90.3
77.0
64.2 60.1
65.2 69.4
82.3
89.7
105.0
113.2
151.8
179.7
185.8
0
50
100
150
200
250
0
1000
2000
3000
4000
5000
6000
7000
Rateper100,000Population
NumberofCases
Year
Cases Rate per 100,000 population
Gonorrhea Cases and Rates by Year
San Diego County, 1999 - 2018

43. 125.7
244.3
0.0
25.0
50.0
75.0
100.0
125.0
150.0
175.0
200.0
225.0
250.0
275.0
300.0
Rateper100,000Population
Year
Females Males
Gonorrhea Rates by Gender and Year
San Diego County, 1999 - 2018

44. 1.4 6.6
292.7
567.3
433.4
224.4
123.4
20.7
0.0 2.7
157.5
577.3
865.8
592.6
333.5
105.4
0
100
200
300
400
500
600
700
800
900
1000
<10 10-14 15-19 20-24 25-29 30-34 35-44 45+
Rateper100,000Population
Age Group
Females Males
Note: Rates exclude 15 cases missing gender or age information.
Rates calculated using 2018 population estimates provided by the Community Health Statistics Unit.
Gonorrhea Rates by Gender and Age
San Diego County, 2018

45. 94.5
19.5
322.3
81.5
57.4
154.6
59.7
522.6
151.6
108.6
0
100
200
300
400
500
600
Native American/
Alaskan Native
Asian/Pacific Islander Black Hispanic White
Rateper100,000Population
Race/Ethnicity
Females Males
Note: 41.7% of cases are missing race/ethnicity or gender information and are not included in rates above.
Rates calculated using 2018 population estimates provided by the Community Health Statistics Unit.
Gonorrhea Rates
by Gender and Race/Ethnicity
San Diego County, 2018

46. CHLAMYDIA & GONORRHEA DIAGNOSIS
 Nucleic acid amplification tests (NAAT)
recommended for women and men
 Optimal specimen:
 Vaginal swab (women)
 First-catch urine (men)
 NAAT recommended for rectal and pharyngeal
testing (MSM)
 Two tests approved by FDA in May 2019
 Disadvantage of NAAT: no antibiotic resistance
testing
 NAAT POC tests https://www.cdc.gov/std/laboratory/2014labrec/default.htm

47. EXTRAGENITAL SCREENING -
MSM
Patton et al, CID 2014
Kent et al, CID 2005

48. EXTRAGENITAL SCREENING –
WOMEN AND MSW
Bamberger et al, STD 2019

49. EXTRAGENITAL SCREENING –
WOMEN
IS IT COST-EFFECTIVE?
 Retrospective analysis of women undergoing extragenital NAAT for GC and CT at Denver
Metro Health Clinic (n=804 visits)
 Prevalence of extragenital infection (women): 2% (16/804) GC and 5% (38/804) CT
 GC: 2% genital and pharyngeal, 0.25% rectal
 CT: 11% genital, 4% pharyngeal, 1.4% rectal
 Urogenital testing alone would have missed 27% (6/22) GC and 14% (14/99) CT
 Isolated infection accounted for 18% (20/111) and 65% (943/1453) of GC/CT infections
in women and MSM respectively.
 Number needed to test to identify one extragenital infection: 40 women, 5 MSM
 Additional Medicaid costs for identifying isolated extragenital infections: $3,851
(women), $480 (men)
Caragol et al, Open Forum Infect Dis 2017

50. GONORRHEA DIAGNOSIS
 Culture:
 Modified Thayer Martin medium
 Antimicrobial susceptibility testing
 Sterile sites (e.g., blood, synovial fluid)
 Gram stain:
 >95% sensitivity, 99% specificity for male
urethral specimens
 Less useful for other specimen types
 Intracellular Gram-negative diplococci
Photo Credit: CDC

52. Neisseria gonorrhoeae — Percentage of Urethral Isolates with
Elevated Minimum Inhibitory Concentrations (MICs) to Azithromycin*
and Ceftriaxone† by Sex and Sex of Sex Partners, Gonococcal Isolate
Surveillance Project (GISP), 2009–2018
* Elevated Azithromycin MIC: ≥2.0 µg/mL.
† Elevated Ceftriaxone MIC: ≥0.125 μg/mL.
ACRONYMS: MSM = Gay, bisexual, and other men who have sex with men; MSW = Men who have sex with women only.

53. GONOCOCCAL ANTIMICROBIAL
SUSCEPTIBILITY – SAN DIEGO, 2018
PCN Resistance: 14.3%
FQ Resistance: 49.0%
Tet Resistance: 25.2%
Source: STD Surveillance 2018:
Gonococcal Isolate Surveillance Project
(GISP) Supplement & Profiles, CDC

54. GONORRHEA TREATMENT
2015 CDC Treatment Guidelines
First-Line: Ceftriaxone 250 mg IM in a single dose
PLUS
Azithromycin 1 gram orally in a single dose
Alternative: Gentamicin 240 mg IM in a single dose
(or Gemifloxacin 320 mg orally in a single dose)
PLUS
Azithromycin 2 grams orally in a single dose
Draft 2020 Guidelines:
• Increase ceftriaxone dose to 500 mg (1 gm if ≥150 kg)
• Anti-chlamydial agent if CT not ruled out
• If cephalosporin allergy, desensitize
• If IM Tx not possible: cefixime 800 mg orally once (+azithro)
• Azithromycin contraindication: doxycycline 100 mg orally BID x 7 days
• Oral antibiotics alone are unlikely to eradicate pharyngeal gonorrhea.
• Alternative Tx for pharyngeal gonorrhea  TOC in 14 days

55. GENTAMICIN INFERIOR TO
CEFTRIAXONE FOR FIRST-LINE GC
TREATMENT
Ross et al, The Lancet 2019

56. ZOLIFLODACIN FOR TREATMENT OF
UNCOMPLICATED GC INFECTIONS
Taylor et al, NEJM 2018;379(19)

57. Chlamydia

58. C. TRACHOMATIS LIFE CYCLE

59. CLINICAL MANIFESTATIONS
 Types A-C: Trachoma or chronic conjunctivitis in Africa & Asia
 Types D-K: asymptomatic infection is common
 Urethritis (may progress to epididymitis)
 Cervicitis (may progress to PID)
 Perihepatitis w/PID – Fitz-Hugh Curtis syndrome
 Mucopurulent conjunctivitis and chlamydial pneumonia in neonates of
infected moms
 Pharyngeal, rectal infections (often asymptomatic)
 Reactive arthritis: urethritis, arthritis, uveitis (antigen cross-reactivity)

60. LYMPHOGRANULOMA VENEREUM
 L1, L2, and L3 serovars
 Tender inguinal &/or femoral
lymphadenopathy
 Self-limited genital ulcer or papule
 Receptive anal intercourse: proctocolitis
 strictures, fistulas
 PCR-based testing for LGV serovars not
widely available
 Doxycycline 100 mg orally BID x 21 days
Photo Credits:
CDC
2015 STD Treatment Guidelines

61. Chlamydia Cases and Rates by Year
San Diego County, 1999 - 2018

62. 814.4
509.8
0
100
200
300
400
500
600
700
800
900
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
Rateper100,000Population
Year
Females Males
Chlamydia Rates by Gender and Year
San Diego County, 1999 - 2018

63. 1.8 53.8
2688.6
4748.9
2575.1
1065.3
393.2
46.80.4 9.0
637.3
1891.5 1772.0
990.8
473.4
127.0
0
400
800
1200
1600
2000
2400
2800
3200
3600
4000
4400
4800
5200
<10 10-14 15-19 20-24 25-29 30-34 35-44 45+
Rateper100,000Population
Age Group
Female Male
Note: Rates exclude 60 cases missing gender or age information.
Rates calculated using 2018 population estimates provided by the Community Health Statistics Unit.
Chlamydia Rates by Gender and Age
San Diego County, 2018

64. CHLAMYDIA TREATMENT
DOXY VS. AZITHRO
UROGENITAL INFECTION
 Meta-analysis by Kong et al (CID 2014)
 Doxy 1.5-2.6% more efficacious for urogenital infections
 Doxy 7% more efficacious for symptomatic urethritis
Group RCT Design CT Cure Rate
Hillis et al (1998)
New York, Florida
Doxy vs. azithro
Women w/cervical CT (n=196), male
partners also enrolled and treated
No difference
Azithro: 94.9%
Doxy: 95.9%
Schwebke et al (2011)
Birmingham, New
Orleans, Durham,
Baltimore
Doxy vs. azithro +/- tinidazole
MSW only w/NGU (n=205)
43% CT, 31% MG, 13% TV, 29% none
Doxy > azithro
Azithro: 77.4%
Doxy: 94.8%
(p=0.011)
Manhart et al (2013)
Seattle
Doxy vs. azithro
Men w/NGU (n= 606 ITT, 232 mITT),
~ 2/3 MSW only, ~1/3 MSM
23% CT, 24% UU-2, 13% MG, 2% TV)
No difference
Azithro: 86.3%
Doxy: 90.0%

65. CHLAMYDIA TREATMENT
DOXY VS. AZITHRO
RECTAL INFECTION
 Meta-analysis by Kong et al (JAC 2015)
 Efficacy difference of 20% in favor of doxycycline (>99% vs. 83%)
 Based on observational studies, multiple limitations
Group/Site(s) RCT Design Comments
Lau et al
(Australia)
Doxy vs. azithro (double-blind,
placebo-controlled)
700 MSM with asymptomatic
rectal CT
mMRA tests and WGS to
differentiate false-pos NAAT,
reinfection, treatment failure
Peuchant et al
(France)
Doxy vs. azithro (open-label)
460 women with urogenital CT,
those with concurrent rectal CT
will be included in the analyses
Additional follow-up (4 mo) for
women with pos rectal CT and
neg vaginal CT at 6-week follow-
up visit; genotyping to evaluate
cervical autoinoculation
NIAID
(Seattle, Boston)
Doxy vs. azithro (double-blind,
placebo-controlled)
177 MSM with asymptomatic
rectal CT
Trial completed in February 2020,
will also assess effect of LGV on
microbiologic cure rates

66. CHLAMYDIA TREATMENT
2015 CDC Treatment Guidelines
Azithromycin 1 gram p.o. as a single dose
OR
Doxycycline 100 mg p.o. BID x 7 days
Draft 2020 Guidelines: Doxycycline first-line, azithro alternative
• Doxy is highly efficacious at all sites in men and women.
• Azithro appears less efficacious for rectal infections and
symptomatic urethral infections
• Many experts recommend doxy for rectal CT infections.

67. WHY THE DIFFERENCE BETWEEN
DOXY AND AZITHRO?
 Heterotypic resistance to macrolides with high organism loads1
 Timing of resumption of sexual activity greater with multidose
regimen1
 Downregulation of immune response in GI tract by chlamydia 
decreased delivery of azithromycin by phagocytes2
 Rectal pharmacokinetic data needed3
1Kong et al CID 2014
2Lau et al, BMC Infectious Diseases 2017
3Khosropour et al, STI 2015

68. Mycoplasma genitalium

69. MYCOPLASMA GENITALIUM
 First identified in 1980
 Lacks cell wall – agents targeting cell wall biosynthesis (e.g., beta lactams) ineffective
 Strongest association with male urethritis:
 12.5-31% of NGU cases
 Recent multisite U.S. study (Bachmann et al, CID 2020):
 Overall prevalence of 28.7%, range from 20.4% (Seattle) to 38.8%
(Greensboro, NC)
 Higher prevalence among Black and Hispanic men and MSW
 Similar to prevalence of CT, higher than that of TV
 20-25% non-CT NGU, ~30% persistent/recurrent urethritis

70. ANTIMICROBIAL RESISTANCE

71. M. GENITALIUM –
ANTIBIOTIC RESISTANCE
 Doxycycline:
 Cure rates ~33%
 Reduction of bacterial load appears to increase efficacy of second agent.
 Azithromycin:
 Cure rates ~67% (Lau et al, BMC Infect Dis 2017)
 Macrolide resistance mutations (MRMs) – positions 2058 or 2059 in 23S ribosomal
RNA gene
 Extended treatment may be more effective than single dose.
 Fluoroquinolones (moxifloxacin):
 Declines in cures from 100% prior to 2010 to 89% (Li et al, Int J STD AIDS 2017)
 ParC (topoisomerase IV subunit A) and GyrA (DNA gyrase subunit A) quinolone-
associated resistance mutations (QAMs)

72. M. GENITALIUM DIAGNOSIS
 NAAT preferred
 Urine, urethral, vaginal and cervical swabs
 1st FDA-approved diagnostic test in January 2019
 Slow growth  culture can take up to 6 months
 PCR for MRMs available in Europe and Australia
 Screening recommended only for patients with compatible syndromes (all or
recurrent/persistent?).
2015 CDC STD Treatment Guidelines

73. RESISTANCE-GUIDED
SEQUENTIAL TREATMENT
Read et al, CID 2019
2.6-log reduction in bacterial load observed after 7 days of doxycycl

74. RESISTANCE-ASSOCIATED MUTATIONS
AND TREATMENT RESPONSE
 MRMs: strong association with macrolide treatment failure
 Among 115 MG-mono-infected men treated initially with azithromycin, persistent
symptoms in 35.1% with MRMs vs. 8.7% without MRMs1
 False-negative results occur with resistance PCR assay
 Prevalence over 60% in two recent studies in U.S. and Australia1-2
 QAMs: weak association with treatment failure
 Expected FQ failure rate based on ParC mutation prevalence 2012-13: 20%2
 Actual failure rate: 7.8% (95% CI 4.2%-12.9%)2
 Prevalence 11.5-20% based on recent reports1-2
1Bachmann et al, CID 2020
2Read et al, CID 2019

75. STI Prophylaxis

76. STI PRE-EXPOSURE PROPHYLAXIS
 30 HIV+ MSM who had syphilis twice or more since HIV diagnosis
 Randomized to daily doxycycline (100 mg) for 36 weeks or incentive
payments for remaining free of STIs
 Doxycycline decreased the risk of testing positive for any STI (OR
0.27, 95%CI 0.09-0.83)
 No significant differences in reported risk behavior between arms
Bolan et al, STD 2015

77. STI POST-EXPOSURE
PROPHYLAXIS
 Open-label extension of ANRS IPERGAY
on-demand PrEP trial in France
 232 MSM and TGW on TDF/FTC PrEP
randomized to 200 mg doxycycline PEP
within 24-72 hours after condomless sex or
no PEP
 Primary endpoint was occurrence of first STI
(CT, NG, syphilis) during 10-month follow-up
 Reduction in occurrence of overall STIs, CT,
syphilis, no effect on gonorrhea
 Similar rates of adverse effects in both
groups
 No risk compensation
Molina et al, Lancet Infectious Diseases 2018

78. DOXYCYCLINE STI PROPHYLAXIS
 More data are needed – five trials are underway or in development.
 There is experience with tetracyclines: (e.g., long-term use for acne; malaria, leptospirosis,
scrub typhus, Lyme disease prophylaxis)
 Surveys indicate that doxycycline prophylaxis is acceptable and of interest to MSM.
 Concerns and challenges:
 Who would benefit the most?
 What dose, regimen, and formulation (monohydrate vs. hyclate) are best?
 What are effects on the microbiome?
 What are the effects on antimicrobial resistance?
 GC – ~23% resistance
 MRSA
 Commensal Neisseria species
Grant et al, CID 2020

79. STIs AND COVID-19
 Impact of COVID-19 on STI burden and patterns remains unclear:
 CDC reported significant decreases in reported gonorrhea (-66%) and
primary/secondary syphilis (-68%) in Mar/Apr 2020 compared to Mar/Apr
2019.
 Social/physical distancing recommendations
 Decreases in routine STI testing and availability of STI services
 In-person visits strongly recommended for individuals at risk for
complications
 PID, syphilis in pregnancy, neurosyphilis symptoms

80. CONTACT INFORMATION
 Winston Tilghman, MD
 Winston.Tilghman@sdcounty.ca.gov
 Office: 619-692-8394
 Consultation Line: 619-609-3245
 Syphilis Histories: 619-692-8501
 www.stdsandiego.org
On May 17, 2016, the County of San Diego Health and Human Services Agency Division
of Public Health Services received accreditation from the Public Health Accreditation Board.