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Sex Differences in the Effect of Vaccines on the Risk of Hospitalization Due to Measles in Guinea-Bissau

Aaby, Peter DMSc*†; Martins, Cesario MD*; Bale, Carlito MD*; Garly, May-Lill MD, PhD*†; Rodrigues, Amabelia PhD*; Biai, Sidu MD*‡; Lisse, Ida M. MD§; Whittle, Hilton MD, FRCP; Benn, Christine S. MD, PhD*†

The Pediatric Infectious Disease Journal: April 2010 - Volume 29 - Issue 4 - p 324-328
doi: 10.1097/INF.0b013e3181c15367
Original Studies

Background: Routine immunizations have non-specific and sex-differential effects on childhood mortality and morbidity in low-income countries; BCG and measles vaccine (MV) may reduce and diphtheria-tetanus-pertussis vaccine (DTP) may increase the mortality of girls relative to boys.

Setting: Urban area in Guinea-Bissau, with a demographic surveillance system and registration of all pediatric hospitalizations. Guinea-Bissau experienced a large outbreak of measles infection in 2003–2004.

Design: We used hospital and community data to examine the impact of other vaccines on the risk of hospitalizations for measles infection. Vaccine efficacy (VE) against hospitalization for children aged 6 to 59 months of age was examined. We assessed whether VE depended on vaccination status for other vaccines and whether the pattern differed for boys and girls.

Main Outcome Measure: Sex-specific vaccine efficacy against hospitalization for children aged 6 to 59 months of age.

Results: The VE depended on sex and the sequence of vaccinations. The VE of MV against hospitalization for measles was better for girls than for boys. Among children who had received MV as the most recent vaccine VE against hospitalization was as high as 96% for girls, but only 81% for boys (P = 0.002). Among children who had received DTP simultaneously with MV or DTP after MV, VE declined for girls (91%) and increased for boys (90%). Compared with having received MV as most recent vaccination, DTP simultaneously with MV or DTP after MV improved the efficacy significantly for boys and the effect was significantly different for boys and girls (P = 0.023). The female-male risk ratio of hospitalization varied significantly, depending on the most recent vaccination (P = 0.014); it was 0.28 (0.11–0.68) for MV alone, but 1.21 (0.82–1.77) for DTP but no MV, and 1.13 (0.58–2.18) for DTP simultaneously with MV or after MV. Among MV-unvaccinated children, BCG-vaccinated girls had a lower risk of measles hospitalization than DTP-vaccinated girls (RR=0.0 (0.0–0.99), exact test).

From the *Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau; †Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark; ‡Servico da Pediatria, Hospital Nacional Simão Mendes, Bissau, Guinea-Bissau; §Department of Pathology, Herlev University Hospital, Herlev, Denmark; and ¶MRC Laboratories, Fajara, The Gambia.

Accepted for publication September 15, 2009.

Supported by the Danish Council for Development Research, Danish Medical Research Council, DANIDA and the EU Commission's INCO program (ICA4-CT-2002–10053). The Bandim Health Project received support from DANIDA. P.A. holds a research professorship grant from the Novo Nordisk Foundation.

C.M., C.B., M.L.G., I.L., H.W., and P.A. were responsible for the measles vaccination trial carried out in the study area; A.R., S.B., and P.A. initiated the study of vaccination status and hospital mortality; C.S.B., C.M., and P.A. implemented the vitamin A supplementation survey; Henrik Ravn, senior statistician, helped with the statistical analysis; P.A. wrote the first draft of the paper and all authors contributed to the final version.

Address for correspondence: Peter Aaby, DMSc, Bandim Health Project, Apartado 861, Bissau, Guinea-Bissau. E-mail: p.aaby@bandim.org.

© 2010 Lippincott Williams & Wilkins, Inc.