Rubella Epidemiology in Africa

1. Rubella Epidemiology in Africa James L Goodson 10th Annual Measles Initiative Meeting Washington D.C. September 13-14, 2011

2. On Behalf of Co-investigators Goodson JL, Masresha B, Dosseh A, Byabamazima C, Nshimirimana D, Cochi S, Susan Reef; Rubella Epidemiology in Africa in the Prevaccine Era, 2002–2009. J Infect Dis. 2011 July 1, 2011;204(suppl 1):S215-S25.

3. Presentation Outline • Background • Rubella epidemiology in Africa in the prevaccine era, 2002-2009 • Methods • Results • Summary

4. Background • 42,440 (Range 9,130 – 97,228)* cases of congenital rubella syndrome (CRS) estimated to occur each year in the WHO African region • Routine CRS surveillance non-existent in the region • Pilot site in Ghana in 1996-97 identified 18 infants with CRS during a 5-month period** • Rubella epidemiology in the region previously not well described *Modelling results, unpublished, Adams E, Vynnycky E **Lawn, J.E., et al., Unseen blindness, unheard deafness, and unrecorded death and disability: congenital rubella in Kumasi, Ghana. American Journal of Public Health, 2000. 90(10): p. 1555-61

5. 46 Countries in the WHO African Region, 2011 Source: WHO and UNICEF, 2011

6. 46 Countries in the WHO African Region, 2011 3 have introduced rubella-containing vaccine Cape Verde Seychelles Mauritius Source: WHO and UNICEF, 2011

7. Methods • Literature review • Surveillance data analysis

8. Methods: Literature Review • PubMed search engine was used to find previously published rubella seroprevalence studies in Africa • A study was included if the article reported seroprevalence results and contained a description of study design, study population, and age group(s) tested

9. Methods: Surveillance Data Analysis • Regional measles case-based surveillance data from 40 countries during 2002–2009 • Data collected following WHO guidelines • Suspected measles case definition • illness with a generalized maculopapular rash and fever, and ≥1 of the following: cough, coryza (runny nose), or conjunctivitis

10. Methods: Surveillance Data Analysis • Blood specimens tested using ELISA • For measles-specific IgM antibody • If results were negative or indeterminate, then tested for rubella-specific IgM • For the analysis of age, sex, and setting (urban/rural), we included countries with ≥30 laboratory-confirmed rubella cases during 2002–2009 • Divided the countries into 4 sub-regions based on geography

11. Results

12. Results: Literature Review • During 1963–2009, there were 22 reports of rubella seroprevalence from 14 (30%) of 46 countries • Rubella susceptibility ranged from 1% – 29% and varied by age group • In the 3 largest studies (N>1000), estimates of rubella susceptibility among women of reproductive age range from 6%–16%

13. Rubella Susceptibility among Women of Reproductive Age, WHO African Region During 1963-2009, sero-susceptibility results for women of reproductive age from 12 countries < 10% 10-24% ≥ 25% Unknown Reference: Goodson JL, Masresha B, Dosseh A, Byabamazima C, Nshimirimana D, Cochi S, Susan Reef; Rubella Epidemiology in Africa in the Prevaccine Era, 2002–2009. J Infect Dis. 2011 July 1, 2011;204(suppl 1):S215-S25.

14. Laboratory-confirmed Rubella Cases, WHO African Region, 2002-2009 (N=25,631) Reference: Goodson JL, Masresha B, Dosseh A, Byabamazima C, Nshimirimana D, Cochi S, Susan Reef; Rubella Epidemiology in Africa in the Prevaccine Era, 2002–2009. J Infect Dis. 2011 July 1, 2011;204(suppl 1):S215-S25.

15. Setting* Cases Female Rural Urban n n % n % n % 25,631 12,271 50 10,527 63 6,255 37 Laboratory-confirmed Rubella Cases by Sex and Setting, WHO African Region, 2002-2009 (N=25,631) *Information on location (rural vs urban) was available for 16,782 (65%) cases Reference: Goodson JL, Masresha B, Dosseh A, Byabamazima C, Nshimirimana D, Cochi S, Susan Reef; Rubella Epidemiology in Africa in the Prevaccine Era, 2002–2009. J Infect Dis. 2011 July 1, 2011;204(suppl 1):S215-S25.

16. Age* Group Women of Reproductive Cases < 1 y 1 - 4 y 5 - 9 y 10 - 14 y ≥ 15 y Age (15 - 49 y) n n % n % n % n % n % n % 25,097 775 3 7,063 28 11,799 47 4,131 16 1,329 5 1,305 5 Laboratory-confirmed Rubella Cases by Age Group, WHO African Region, 2002-2009 (N=25,631) *Information on age was available for 25,097 (99%) cases Reference: Goodson JL, Masresha B, Dosseh A, Byabamazima C, Nshimirimana D, Cochi S, Susan Reef; Rubella Epidemiology in Africa in the Prevaccine Era, 2002–2009. J Infect Dis. 2011 July 1, 2011;204(suppl 1):S215-S25.

17. Frequency of Laboratory-confirmed Rubella Cases by Age in Years, 2002-2009, WHO African Region (N=25,097) Overall, mean age of cases was 7.3 years (IQR=4.2–9.0 y) Information on age and setting available for 16,627 (65%) cases In urban settings, mean age was 6.8 years (IQR=3.9–8.5 y) In rural settings, mean age was 7.5 years (IQR=4.2–9.8 y) (P=.004) Reference: Goodson JL, Masresha B, Dosseh A, Byabamazima C, Nshimirimana D, Cochi S, Susan Reef; Rubella Epidemiology in Africa in the Prevaccine Era, 2002–2009. J Infect Dis. 2011 July 1, 2011;204(suppl 1):S215-S25.

18. Laboratory-confirmed Rubella Cases by Month of Rash Onset, 4 Geographic Subregions, 2002–2009, WHO African Region South distinct annual seasonality consistently few cases Jan–June gradual increases, peaks Sept–Oct East reporting varied biphasic, peaks Mar–Apr, Sept–Oct troughs Dec–Jan and May–June Central data were sparse peaks generally Feb–Mar troughs Sept–Nov West distinct annual seasonality sharp increase Jan, peaks Mar–Apr declines May, troughs Oct–Dec Reference: Goodson JL, Masresha B, Dosseh A, Byabamazima C, Nshimirimana D, Cochi S, Susan Reef; Rubella Epidemiology in Africa in the Prevaccine Era, 2002–2009. J Infect Dis. 2011 July 1, 2011;204(suppl 1):S215-S25.

19. Limitations • Seroprevalence studies, small convenience samples, results not representative • The surveillance data represents a small fraction of all rubella cases • Cases were detected through surveillance designed to detect measles • 20%–50% rubella infections do not have rash, therefore, clinical presentation may not meet suspected measles case definition • Potential reporting bias toward groups wherein suspected measles cases occurred, such as in younger age groups

20. Summary: Rubella Epidemiology in Africa • Estimates of rubella susceptibility among adults range from 1%–29% • In the 3 largest studies, estimates of rubella susceptibility among women of reproductive age range from 6%–16% • Rubella virus is circulating widely in Africa • Primarily infecting young children • By 15 years of age most have immunity from natural infection • 5% of reported rubella cases occur in women of reproductive age • Suggests rubella infection during pregnancy, potential CRS, remains largely undetected

21. Measles Initiative Working Together to Save Lives IFFIm Vodafone Thank You Japanese Government

22. Back-up Slides

23. Discussion – Age Distribution • During prevaccine era in Europe and the Americas • Age distribution was similar to that in Africa, primarily a childhood disease, mainly among 5- to 9-year-olds • In the United States • 80% of reported cases occurred by 14 years of age • 92% by 20 years of age • However, seroprevalence studies estimated susceptibility among those17–22 years of age was 15%–20%

24. Discussion – Urban vs. Rural • During prevaccine era in Europe, Americas, and Asia • Immunity to rubella in rural settings was lower than in urban settings; and is consistent with our finding of an older mean age of reported cases in rural settings than in urban settings in Africa. • The significantly younger mean age of reported cases in urban settings compared with that of rural settings in Africa may be due to rubella infection occurring at younger age in areas with high population density and contact rates.

25. Discussion – Seasonality In the United States, prevaccine era, annual seasonality of rubella was observed, with an increase in cases occurring in the early winter, peaking in March and decreasing to a low point in late summer and autumn; in general, annual seasonal peaks in rubella cases occur during springtime in temperate climates. We found similar seasonality in the South subregion of Africa, which includes countries located in the southern temperate zone.

26. Discussion – Seasonality In the United States, prevaccine era, annual seasonality of rubella was observed, with an increase in cases occurring in the early winter, peaking in March and decreasing to a low point in late summer and autumn; in general, annual seasonal peaks in rubella cases occur during springtime in temperate climates. We found similar seasonality in the South subregion of Africa, which includes countries located in the southern temperate zone.

27. Rubella Disease • 20-50% of infections are asymptomatic • Prodrome • Rare in children • Adolescents/adults: low grade fever, malaise, lymphadenopathy, upper respiratory symptoms lasts1- 5 days • Rash • Maculopapular • Begins on face and head • Usually persists 3 days • Other symptoms • Lymphadenopathy: postauricular, posterior cervical, and suboccipital • Conjunctivitis

28. Congenital Rubella Syndrome • Infection in pregnancy, most dangerous <12 weeks gestation • May lead to fetal death or premature delivery • Hearing impairment, cataracts, heart defects, microcephaly, developmental delay, bone alterations, liver and spleen damage • Organ specificity generally related to stage of gestational infection

29. Rubella Epidemiology • Reproductive number (R0) lower than for measles • High coverage with single dose of rubella vaccine can provide herd immunity • Usual inter-epidemic interval: 6-9 years • Rubella /CRS elimination goal achievable by targeting children through existing measles control strategy but women of child bearing age must also be covered

30. Results: Literature Review • 3 studies of women of reproductive age with N>1000 • 94.1% (95% CI, 93.0%–95.2%) • women 14–18 years of age (N=1,696) in Ethiopia • Gabreselassi & Abebe1985 • 90.1% (95% CI, 89.2–91.1) • women 15–45 years of age (N=3,471) in Senegal • Dromigny et al. 2003 • 84.0% (95% CI, 83.0%–85.0%) • women 15–34 years of age (N=4,866) in Cote d’Ivoire • Vrinat et. Al 1978