The Zimbabwe STI Etiology Study - PowerPoint Presentation

Slide1

The Zimbabwe STI Etiology StudySlide2

This project has been supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through Cooperative Agreement between the Centers for Disease Control and Prevention and the University of Zimbabwe Department of Community Medicine SEAM Project under the terms of Cooperative Agreement Number:  1U2GGH000315-01Slide3

This project was approved by the Medical Research Council of Zimbabwe (MRCZ), the Research Council of Zimbabwe (RCZ), the Joint Research Ethical Commission (JREC) and the Institutional Review Board of the U.S. Centers for Disease Control and Prevention (CDC)Slide4

Collaborators

Department of Community Medicine, University of Zimbabwe School of MedicineProf.

Mufuta Tshimanga, Principal InvestigatorDr. Gerald ShambiraZimbabwe Ministry of Health and Child Care

Dr. Owen

Mugurungi

Dr. More Mungati

Dr.

Mutsa

Manghara

Ms. Anna MachihaSlide5

Collaborators

U.S. Centers for Disease Control and Prevention – Zimbabwe OfficeDr. Peter Kilmarx

Elizabeth Gonese, MPH

Amy Herman-Roloff, MPH

Zimbabwe Community Health Intervention Research (ZiCHIRe)

Vitalis Kupera, RN: Field Supervisor

Luanne Rodgers, BA: Laboratory SupervisorSlide6

Collaborators

National Institute of Communicable DiseasesProf. David LewisRietmeijer Consulting

Prof. Kees RietmeijerSlide7

Background

In many countries sexually transmitted infections (STIs) are treated syndromically with combinations of antibiotics that cover the most prevalence causative infectious agents

Periodic surveys are necessary to determine current etiologic patterns of most common STI syndromesSlide8

Primary Aims

To assess the microbiological etiology of the following sexually transmitted infection (STI) syndromes:Vaginal discharge in women

Urethral discharge in menGenital ulcer disease in men and womenSlide9

Secondary Aims

To assess the association between HIV infection and STI syndromesTo assess the prevalence of gonorrhea and chlamydia among men and women with genital ulcer disease

To assess the performance of novel diagnostic platforms, including:GeneXpert for diagnosis of gonorrhea and chlamydia

Standard Diagnostics Bioline DUO for the simultaneous rapid test diagnosis of HIV and syphilisSlide10

Study Population

A total of 600 patients: 200 women with vaginal discharge

200 men with urethral discharge200 men and women with genital ulcer disease6 regionally diverse clinics were selected based on high numbers of reported STI

Harare: Mbare (H1) and Budiriro clinics (H2)

Bulawayo:

Nkulumane

(B1) and

Khami

Road (B2) Clinics

Beitbridge:

Dulibadzimu

Clinic (D1)

Gutu: Gutu Road Clinic (G1)Slide11

Methods - 1

A specially trained study team of 3 nurses was deployed sequentially to each of the participating clinics

Study participants were recruited and consented on the basis of their symptomsData were collected using a paper-based standardized questionnaire and entered into an online database after completion of the visit

All forms and samples shipped overnight to research laboratory in HarareSlide12

Data Collection

DemographicsClinical history Type and duration of symptoms

STI history and HIV statusSexual historyNumber of partnersCondom use

Commercial SexSlide13

Specimens Collected

Blood (all patients)

Men with urethral discharge

Urethral smears for Gram stain

Urine for NAAT

Women with vaginal discharge

Vaginal smears for Gram stain

Vaginal swabs for NAAT

Women and men with genital ulcer disease

Ulcer swabs for NAATSlide14

Laboratory Methods

Genital Discharge Syndromes

Nucleic Acid Amplification Tests (NAAT)

Gold Standard: Multiplex polymerase chain reaction (M-PCR, NICD*)

C. trachomatis

N. Gonorrhoeae

T. vaginalis

M. genitalium

Probetec

(Becton Dickinson)

C. trachomatis

and N.

gonorrhoeae

Xpert

CT/NG (Cepheid)

C. trachomatis

and

N. gonorrhoeae

*NICD: National Institute for Communicable Diseases, Johannesburg, South AfricaSlide15

Laboratory MethodsGenital Ulcer Disease

Nucleic Acid Amplification Tests (NAAT)

M-PCR (NICD*)

T. pallidum

H. ducreyi

Herpes simplex virus (HSV)

C. trachomatis

(LGV strains

Probetec

(Becton Dickinson)

C. trachomatis

and N.

gonorrhoeae

Xpert

CT/NG (Cepheid)

C. trachomatis

and

N. gonorrhoeae

*NICD: National Institute for Communicable Diseases, Johannesburg, South AfricaSlide16

Laboratory Methods

HIV Serology

Determine (screening)

First Response

(confirmatory)

ChemBio

(tie-breaker)

Syphilis Serology

Treponemal

TPHA

SD Bioline

Non-treponemal: RPRSlide17

ResultsSlide18

STI Surveillance in ZimbabweSlide19

Recruitment (N=600)

Source: Zimbabwe STI Aetiology Study, 2015Slide20

Recruitment by Site and STI Syndrome (N=600)

Source: Zimbabwe STI Aetiology Study, 2015Slide21

Demographics by Site (N=600)

Age

Mean: 28.6 Median: 27

Women: Mean: 27.6 Median: 26

Men: Mean: 29.5 Median: 29 (

p

<0.01)Slide22

Demographics by Site (N=600)

Age

Mean: 28.6 Median: 27

Women: Mean: 27.6 Median: 26

Men: Mean: 29.5 Median: 29 (

p

<0.01)Slide23

Sexual BehaviorReporting >1 Partner in Past 3 Months

Source: Zimbabwe STI Aetiology Study, 2015Slide24

Condom Use Last Sexual EncounterCasual Partner

Source: Zimbabwe STI Aetiology Study, 2015Slide25

Condom Use Last Sexual EncounterMain Partner

Source: Zimbabwe STI Aetiology Study, 2015Slide26

Sexual Behavior

Reporting Commercial Sex in Past 3 Months

Source: Zimbabwe STI Aetiology Study, 2015Slide27

Perceived HIV Status(N=600)

Source: Zimbabwe STI Aetiology Study, 2015Slide28

HIV Status Actual(N=489)

Source: Zimbabwe STI Aetiology Study, 2015Slide29

Urethral Discharge Syndrome (UDS)

MenSlide30

Men with Urethral Discharge Syndrome:

Gonorrhea:

137 (68%)

>10 WBC/HPF:

12 (6%)

1-9 WBC/ HPF:

16 (8%)

Negative:

35 (18%)

Gram Stain Results - Men

N = 200

(Gram Negative

Intracellular

Diplococci

)

Source: Zimbabwe STI Aetiology Study, 2015Slide31

%

Aetiology of Male

Urethral Discharge Syndrome by Multiplex PCR (N=200)

Source: Zimbabwe STI Aetiology Study, 2015Slide32

Urethral Discharge Syndrome – MenSingle vs. Multiple Infections

Single infection: 121 (60.5%)

NG 106

CT 9

TV 2

MG 4

Dual infections: 40 (20%)

NG+CT: 34

NG+TV: 4

NG+MG: 1

TV+MG: 1

3 infections: 2 (1%)

NG+CT+TV:1

NG+CT+MG: 1

4 infections: None

No infection: 37 (18.5%)

36/43 (84%) CT infections were co-infections

41/147 (28%) GC infections were co-infections

Source: Zimbabwe STI Aetiology Study, 2015Slide33

CT, TV, and MG infections were more common among men with <10 WBC/HPF (12/24; 50%) compared to men with >10 WBC/HPF (3/97; 4 %) p<0.001 (chi square)

Male

UDS Aetiology

in Relation to Gram Stain Results (Single Infections; N=121)

N=97

N=24

Source: Zimbabwe STI Aetiology Study, 2015Slide34

Variations in the Aetiology of Urethral Discharge by Clinic (N=200)

Source: Zimbabwe STI Aetiology Study, 2015Slide35

HIV and Syphilis Co-infections

HIV: 44/152 (29%) Syphilis: 9/152 (5.9%)No significant associations with any of the urethritis pathogensSlide36

Vaginal Discharge Syndrome WomenSlide37

Gram Stain Results – WomenN 200

Women with Vaginal Discharge Syndrome:

Gonorrhea:

18 (9%)

BV

: 49 (25%)

Yeast:

41 (21%)

Normal: 82

(45%)

(Gram Negative

Intracellular

Diplococci

)

Source: Zimbabwe STI Aetiology Study, 2015Slide38

Aetiology of Vaginal Discharge

Source: Zimbabwe STI Aetiology Study - 2016Slide39

Aetiology of

Vaginal Discharge syndrome by Multiplex PCR (N=200)

Source: Zimbabwe STI Aetiology Study, 2015Slide40

Single infection: 62 (31%)

NG: 24

CT: 9TV : 21

MG : 8

Dual infections: 18 (9%)

NG +CT: 7

NG+TV: 6

CT+MG: 3

NG+MG: 1

TV+MG: 1

3 infections: 10 (5%)

NG+CT+TV: 9

NG+MG+TV: 1

4 infections: None

No infection: 110 (55%)

Vaginal Discharge Syndrome – Women

Single vs. Multiple Infections

Number of InfectionsSlide41

HIV and Syphilis Co-infections

HIV: 65/159 (40.9%) Syphilis: 21/159 (13.2%)No significant associations with any of the discharge-associated pathogensSlide42

Genital Ulcer DiseaseMen and WomenSlide43

GRA22HSV:

Genital Ulcer Disease - Multiplex PCR Results

Of those with pathogens detected (

n

=102)

HSV: 66.6%

T. pallidum

: 22.5%

Both: 9%

C. trachomatis

(LGV): 1.9%

Source: Zimbabwe STI Aetiology Study, 2015Slide44

Multiplex PCR results varied significantly (

p

<0.05) by recruitment clinic with lower rates of HSV at the Harare clinics

M-PCR Results by Clinic

Source: Zimbabwe STI Aetiology Study, 2015Slide45

M-PCR Results by HIV Status

Multiplex PCR results varied significantly (

p

<0.01) by HIV status.

HSV rates were 51.6% for persons with HIV infection compared to 25.6% for those uninfected with HIV

Source: Zimbabwe STI Aetiology Study, 2015Slide46

Predictors of HSV Infection – Multivariate Analysis

AOR: Adjusted Odds Ratio 95% C.I.: 95% Confidence IntervalsSlide47

Chlamydia and Gonorrhea Positivity by STI Syndrome

Source: Zimbabwe STI Aetiology Study, 2015Slide48

Treponemal/Non-treponemalPositivity by Syndrome

Source: Zimbabwe STI Aetiology Study, 2015Slide49

Gonococcal and chlamydia infections present in 26% of GUD cases.

69% did not have comcomittant genital discharge and thus would not have been treated using syndromic approachSlide50

HIV Positivity by STI Syndrome

Source: Zimbabwe STI Aetiology Study, 2015Slide51

Summary

Urethral discharge among men was mostly caused by gonorrhea single infections followed by gonorrhea/chlamydia dual infections

In men with less inflammatory response, chlamydia was significantly more commonSlide52

Summary

Gonorrhea, although less common among women with vaginal discharge, was the most common pathogen identified, followed by trichomoniasis and chlamydiaAlmost 50% of vaginal discharge was associated with BV or yeast infections

Slide53

Summary

Mycoplasma genitalium was uncommonly identified among both men and women with genital dischargeSlide54

Summary

Among women and men with genital ulcer disease, HSV infections were the most commonly identified, followed by primary syphilisHSV infections were highly associated with concurrent HIV infection

No cases of H. ducreyi infections identifiedSlide55

Summary

Gonorrhea and chlamydia prevalence was high among men and women with genital ulcer diseaseAmong these, close to 70% would not have been treated using syndromic approachSlide56

Conclusions

Source:Slide57

Conclusions

Current syndromic management appears to adequately cover the most common pathogens associated with genital discharge syndromes or genital ulcer disease in Zimbabwe.However, the prevalence of gonorrhea and chlamydia is high among persons with GUD and, unless simultaneously diagnosed with genital discharge, inadequately covered by syndromic management for GUD alone.Slide58

Conclusions

The relatively high prevalence of primary syphilis among persons with genital ulcer disease as well as the high prevalence of syphilis serological markers among all persons with STI in this study, warrants further investigations into the current epidemiology of syphilis in Zimbabwe, especially among pregnant women.Slide59

Conclusions

There was an overall very high (~40%) prevalence of HIV infection among patients with all STI syndromes

These results are difficult to interpret in a cross-sectional study and require further investigations, including asymptomatic STIs among HIV-infected persons

Regardless, the concurrence of HIV infections and

STIs

promulgate HIV transmission, especially from persons that are not virally suppressedSlide60

Conclusions

Prevention efforts among persons with STI syndromes continue to be a high public health prioritySlide61

Limitations

Results from 6 clinics not generalizable Patients with STI syndromes are not representative of all persons with STI infections

Persons with chlamydia are less likely to symptomatic and therefore less likely to present to STI clinicsCo-location of HIV and STI clinic may bias towards higher HIV prevalence among those with STI syndromes in our studySlide62

Thank You!!

Source:Slide63

Questions? Comments?

More information:

kees@rietmeijer.us