1. The Zimbabwe STI Etiology Study

2. 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:  1U2GGH

3. 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)

4. Collaborators
Department of Community Medicine, University of Zimbabwe School of Medicine
Prof. Mufuta Tshimanga, Principal Investigator
Dr. Gerald Shambira
Zimbabwe Ministry of Health and Child Care
Dr. Owen Mugurungi
Dr. More Mungati
Dr. Mutsa Manghara
Ms. Anna Machiha

5. Collaborators
U.S. Centers for Disease Control and Prevention – Zimbabwe Office
Dr. Peter Kilmarx
Elizabeth Gonese, MPH
Amy Herman-Roloff, MPH
Zimbabwe Community Health Intervention Research (ZiCHIRe)
Vitalis Kupera, RN: Field Supervisor
Luanne Rodgers, BA: Laboratory Supervisor

6. Collaborators National Institute of Communicable Diseases
Prof. David Lewis
Rietmeijer Consulting
Prof. Kees Rietmeijer

7. 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 syndromes

8. Primary Aims
To assess the microbiological etiology of the following sexually transmitted infection (STI) syndromes:
Vaginal discharge in women
Urethral discharge in men
Genital ulcer disease in men and women

9. Secondary Aims
To assess the association between HIV infection and STI syndromes
To 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 syphilis

10. Study Population A total of 600 patients:
200 women with vaginal discharge
200 men with urethral discharge
200 men and women with genital ulcer disease
6 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)

11. 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 symptoms
Data 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 Harare

12. Data Collection Demographics Clinical history Sexual history
Type and duration of symptoms
STI history and HIV status
Sexual history
Number of partners
Condom use
Commercial Sex

13. 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 NAAT

14. 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)
*NICD: National Institute for Communicable Diseases, Johannesburg, South Africa

15. Laboratory Methods Genital 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)
*NICD: National Institute for Communicable Diseases, Johannesburg, South Africa

16. Laboratory Methods HIV Serology Determine (screening)
First Response (confirmatory)
ChemBio (tie-breaker)
Syphilis Serology
Treponemal
TPHA
SD Bioline
Non-treponemal: RPR

17. Results

18. STI Surveillance in Zimbabwe

19. Recruitment (N=600)
Source: Zimbabwe STI Aetiology Study, 2015

20. Recruitment by Site and STI Syndrome (N=600)
Source: Zimbabwe STI Aetiology Study, 2015

21. 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)

22. 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)

23. Sexual Behavior Reporting >1 Partner in Past 3 Months
Source: Zimbabwe STI Aetiology Study, 2015

24. Condom Use Last Sexual Encounter Casual Partner
Source: Zimbabwe STI Aetiology Study, 2015

25. Condom Use Last Sexual Encounter Main Partner
Source: Zimbabwe STI Aetiology Study, 2015

26. Sexual Behavior Reporting Commercial Sex in Past 3 Months
Source: Zimbabwe STI Aetiology Study, 2015

27. Perceived HIV Status (N=600)
Source: Zimbabwe STI Aetiology Study, 2015

28. HIV Status Actual (N=489)
Source: Zimbabwe STI Aetiology Study, 2015

29. Urethral Discharge Syndrome (UDS) Men

30. Gram Stain Results - Men N = 200
(Gram Negative
Intracellular Diplococci)
Men with Urethral Discharge Syndrome:
Gonorrhea: 137 (68%)
>10 WBC/HPF: 12 (6%)
1-9 WBC/ HPF: 16 (8%)
Negative: 35 (18%)
Source: Zimbabwe STI Aetiology Study, 2015

31. Aetiology of Male Urethral Discharge Syndrome by Multiplex PCR (N=200)%
Aetiology of Male Urethral Discharge Syndrome by Multiplex PCR (N=200)
Source: Zimbabwe STI Aetiology Study, 2015

32. Urethral Discharge Syndrome – Men Single 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, 2015

33. 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=24
N=97
Source: Zimbabwe STI Aetiology Study, 2015

34. Variations in the Aetiology of Urethral Discharge by Clinic (N=200)
Source: Zimbabwe STI Aetiology Study, 2015

35. HIV and Syphilis Co-infections
No significant associations with any of the urethritis pathogens

36. Vaginal Discharge Syndrome Women

37. Gram Stain Results – Women N 200
(Gram Negative
Intracellular Diplococci)
Women with Vaginal Discharge Syndrome:
Gonorrhea: 18 (9%)
BV: 49 (25%)
Yeast: 41 (21%)
Normal: 82 (45%)
Source: Zimbabwe STI Aetiology Study, 2015

38. Aetiology of Vaginal Discharge
Source: Zimbabwe STI Aetiology Study

39. Aetiology of Vaginal Discharge syndrome by Multiplex PCR (N=200)
Source: Zimbabwe STI Aetiology Study, 2015

40. Vaginal Discharge Syndrome – Women Single vs. Multiple Infections
Single infection: 62 (31%)
NG: 24
CT: 9
TV : 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%)
Number of Infections

41. HIV and Syphilis Co-infections
No significant associations with any of the discharge-associated pathogens

42. Genital Ulcer Disease Men and Women

43. Genital Ulcer Disease - Multiplex PCR Results
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%
200 Men and 200 Women
with GUD
HSV: 68 (34%)
Type 1: 1 (0.5%)
T. pallidum (Tp): 23 (11.5%)
Both HSV and Tp: 9 (4.5%)
C. trachomatis (LGV): 2 (1%)
1 co-infected with Tp
H. ducreyi: 0
None: 98 (49%)
Of those with pathogens detected (n=102)
HSV: 66.6%
T. pallidum: 22.5%
C. trachomatis (LGV): 1.9%
Source: Zimbabwe STI Aetiology Study, 2015

44. M-PCR Results by Clinic
Multiplex PCR results varied significantly (p<0.05) by recruitment clinic with lower rates of HSV at the Harare clinics
Source: Zimbabwe STI Aetiology Study, 2015

45. 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, 2015

46. Predictors of HSV Infection – Multivariate Analysis
AOR: Adjusted Odds Ratio 95% C.I.: 95% Confidence Intervals

47. Chlamydia and Gonorrhea Positivity by STI Syndrome
Source: Zimbabwe STI Aetiology Study, 2015

48. Treponemal/Non-treponemal Positivity by Syndrome
Source: Zimbabwe STI Aetiology Study, 2015

49. 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 approach
In conclusion
Urethral or vaginal GC and or CT infections were present in 52 (26%) of participants with genital ulcer disease.
Of these 36 (69%) would not have been treated according to the current syndromic management guidelines
These results raise concerns about the appropriateness of syndromic management, particularly among patients with genital ulcer disease

50. HIV Positivity by STI Syndrome
Source: Zimbabwe STI Aetiology Study, 2015

51. 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 common

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

53. Summary
Mycoplasma genitalium was uncommonly identified among both men and women with genital discharge

54. Summary
Among women and men with genital ulcer disease, HSV infections were the most commonly identified, followed by primary syphilis
HSV infections were highly associated with concurrent HIV infection
No cases of H. ducreyi infections identified

55. Summary
Gonorrhea and chlamydia prevalence was high among men and women with genital ulcer disease
Among these, close to 70% would not have been treated using syndromic approach

56. Conclusions
Source:

57. 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.

58. 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.

59. 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 suppressed

60. Conclusions
Prevention efforts among persons with STI syndromes continue to be a high public health priority

61. 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 clinics
Co-location of HIV and STI clinic may bias towards higher HIV prevalence among those with STI syndromes in our study

62. Thank You!!
Source:

63. More information: kees@rietmeijer.us
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