1. Untreated Infectious Diseases and Infertility Prevention in Africa
JOE LEIGH SIMPSON, M.D., FACOG, FACMG, FRCOG
Senior Vice President Research and Global Programs
March of Dimes Foundation
Immediate Past President International Federation Fertility Societies (IFFS)
UNESCO – Merck Africa Research Summit Addis Ababa; September 28, 2016

2. Prevalence of Primary Infertility
<1%
1% %
2% %
>3%
Newman et al., PLOS Medicine;2012

3. Prevalence of Secondary Infertility
<9%
9% %
11% %
>13%
Newman et al., PLOS Medicine; 2012

4. Infertility Etiology: 50% male factor, 50% female factor
10% of all couples do not become pregnant
Etiology: 50% male factor, 50% female factor
Non-infectious
Ovarian, testicular, spermatogenesis
Autoimmune, non-reproductive systemic medical illnesses
Infectious (35%)
Etiology

5. Infertility Associated with Treatable Sexually Transmitted Diseases (STDs)
Transmission greater male to female
Long term consequences greater in women than in men
Presence of one STD predisposes to another
Anatomic causes: salpingitis, endometritis, tubal occlusion

6. Untreated Sexually Transmitted Diseases and Infertility
Salpingitis: 15% prevalence in reproductive age women % absolute rate of infertility
1 episode 11% infertility
2 episode 23% infertility
3 episode 54% infertility
Readily treatable

7. Curable STDs Chlamydia, Gonorrhea, Syphillis, Trichomoniasis
Newman et al., PLOS Medicine
2012

8. Chlamydia Trachomatis: Why so Frequently the Cause of Infertility?
Intracellular bacteria, requiring viable host cells
Relatively long incubation period
Often asymptomatic
70 % in female; 50% in male
4. Non-specific signs in females: vaginal and cervical discharge, post coital bleeding due to “friable” cervix

9. Screening for Chlamydia
Assay
Nucleic acid amplification tests (NAAT): Endocervix, vagina, urine, urethra
NAAT superior to culture and other tests
Population Screening
Women <25 years and older women at increased risk
Women treated during pregnancy should be retested 3 months after infection

10. Screening and Treatement for Chlamydia
Treatment
Azithromycin (single oral dose)
Doxycycline (7d) (oral)
Tetracycline (7d) (oral)
Erythromycin (7d) (oral)
Ofloxacin (7d) (oral)
Follow-up tests essential

11. (Neisseria gonorrhoeae)
Gonorrhea
(Neisseria gonorrhoeae)
78M new worldwide cases annually, with highest prevalence in Africa and Western Pacific
0.8% female; 0.6% male
Adheres to mucosal cells; transported by pinocytosis into epithelial cells
Persists by ability to alter host environment (immuno-evasive mechanisms) that include Ig A protease, cell-adherence mechanisms

12. Screening for Gonorrhea
Assay
Population Screening
NAAT: Nucleic acid amplification tests (urine, endocervix, or vagina); preferred to culture
Women <25 years and older women at increased risk
Women treated during pregnancy should be retested 3 months after infection

13. (Neisseria gonorrhoeae) Assume more than a single STD
Gonorrhea
(Neisseria gonorrhoeae)
Treatment
Ceftriaxone plus azithromycin (oral)
Ceftriaxone (intramuscular) or
Cefixime (oral)
Spectinomycin (intramuscular)
Assume more than a single STD

14. Prevalence of Syphilis (18M worldwide)
Europe:
0.16%
Mediterranean
0.06%
Pacific:
0.33%
Asia:
0.62%
Africa:
2.15%
>=5%
>+1.0 to 4.9%
>=0.5 to 0.9%
<=0.5%
Newman et al., PLOS Medicine
2013

15. Syphilis Primary Infection incubation; [21d (9-90)] (chancre)
But, resolution even without treatment (benzamine penicillin)
“Asymptomatic” Hematogenous spread until immune response (4 – 10 weeks)
Secondary
Maculopapular eruption resolves 2 – 6 weeks
Latent Phase
Tertiary syphlis

16. Screening for T. Pallidum
Nontreponemal
Rapid plasma reagin (RER)
Venereal Disease Research Lab (VDRL)
Treponemal
Fluorescent Treponemal Antibody Absorption (FTP-ABS)
Treponemal Pallidum Passive Aggltination (TP-PA)
Remain positive lifelong

17. Research Implications for STD
(WHO, 2016)
Chlamydia
Clinical vs microbiological cases
Side effects that decrease compliance
Concomitant HIV transmission
Partner transmission
N. Gonorrhea
New drugs combination
Targeted population
Treatment failures / resistance

18. “Social” Infertility Syphilis (annually) Miscarriages and stillborn
▪ 143,000 fetal deaths
▪ 102,000 neonatal deaths (congenital syphilis)
Preterm birth neonatal death
In many cultures a pregnancy without a liveborn is even worse than never conceiving

19. Preterm births – where are the highest rates?1
Preterm births – where are the highest rates?
11 countries with preterm birth rates over 15%
Malawi
Congo
Comoros
Zimbabwe
Equatorial Guinea
Mozambique
Gabon
Pakistan
Indonesia
Mauritania
Botswana
Estimates for 184 countries for 2010
Of the 11 countries with the highest rates, 9 are in Africa
Note: rates by country are available on the accompanying wall chart. Not applicable=non WHO Members State
Source: Blencowe et al National, regional and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications

20. Preterm Birth Rate in LIC
lifestlye+
infection
nutrition
contraception

21. Infectious Causes of Preterm Birth Rate
urinary tract, malaria, HIV, syphilis, bacterial vaginosis (chlamydia)
infection

22. Phenotypes of Preterm Birth in High Capacity Facilities (Africa)
Spontaneous preterm births
88.1%
Provider-initiated Preterm Births 11.8%
Preterm birth,
labour status unknown
0.2%
Vogel; 2016

23. Conclusion
Infections frequently lead to tubal / endometrial abnormalities that often result in infertility
Infectious causes of infertility may be asymptomatic and are readily treatable
Universal screening in sexually active populations needed because many (70% females for chlamydia) asymptomatic
WHO has identified research priorities for each infectious agent