INT J TUBERC LUNG DIS 4(1):26–31 © 2000 IUATLD Sex differences in the epidemiology of tuberculosis in San Francisco A. N. Martinez,* J. T. Rhee, † P. M. Small, ‡ M. A. Behr § * Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, Divisions of † Epidemiology and ‡ Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California, USA; § Division of SUMMARY Infectious Diseases, McGill University Health Centre, Montreal, Quebec, Canada SETTING: Worldwide differences in sex-specific tuber- culosis case rates remain fundamentally unexplained. OBJECTIVE: To explore various factors that may explain sex differences in tuberculosis incidence rates for San Francisco from 1991–1996. DESIGN: A retrospective epidemiologic analysis of sex- specific tuberculosis incidence rates in San Francisco from 1991–1996. Stratified analyses were performed on age at diagnosis, racial/ethnic group, human immunode- ficiency virus (HIV) status, and place of birth. Molecular fingerprinting with IS6110 data was used to study sex differences in the incidence of disease for recently trans- mitted and reactivated cases of tuberculosis. RESULTS: In the study period, the male to female inci- dence rate ratio was 2.1 (95%CI 1.9–2.3). Stratified analyses revealed differences in sex-specific rates after the age of 14 and the highest male:female ratios were seen in the US-born, white, and black populations. High ratios were also observed for cases with clustered finger- prints, similar to those observed for the US-born popu- lation. In sub-populations with predominantly reacti- vated cases of tuberculosis, ratios were also above unity after adolescence, but the effect was less pronounced. CONCLUSION: The ongoing transmission of tuberculo- sis in the US-born population is one of the factors that explains the difference in sex-specific rates of disease in San Francisco. Observed differences in tuberculosis rates between the sexes may be due to a difference in trans- mission dynamics rather than diagnosis or reporting biases. KEY WORDS: tuberculosis; sex; gender; epidemiology THE REASONS for global sex differences in the epi- demiology of tuberculosis are largely unknown. An international research meeting on gender and tuber- culosis in 1998 reported that tuberculosis is now the single biggest infectious killer of women in the world, and the leading cause of death among women of reproductive age. 1 In general, a higher proportion of male case notifications exists worldwide, but a breakdown of case rates by geographic region reveals variable male to female rate ratios. For instance, in Zambia, Uganda, and Congo, incidence and mortal- ity rates in young females are higher than or equal to those in males of the same age. 2 Two reviews published in the last year detail the current status of global sex differences in tuberculo- sis. 3,4 Two hypotheses to explain such variability have been presented: 1) under-diagnosis or under-reporting of tuberculosis in females, and 2) real differences in infection with Mycobacterium tuberculosis and/or pro- gression to active disease. The first hypothesis encom- passes socio-cultural factors including stigmatization of females with tuberculosis and impaired access to health care. The second hypothesis reflects socio- cultural and biologic factors that influence opportuni- ties for exposure to M. tuberculosis and conditions that foster progression and reactivation. We have explored the latter hypothesis in San Francisco, where diagnosis and reporting of tuberculosis cases is not expected to vary for males and females. Current tuberculosis epidemiology in San Fran- cisco represents a blend of ongoing transmission in the US-born 5 and reactivation disease in the foreign- born, 6 and we have assessed how sex differences in tuberculosis rates varied according to the different transmission dynamics in these two populations. The use of molecular fingerprinting, which helps distin- guish recent spread from reactivation of latent infec- tion, 7 permitted a refined understanding of sex differ- ences in tuberculosis case rates. STUDY POPULATION AND METHODS The study population included all reported cases of tuberculosis (pulmonary and extra-pulmonary) in Correspondence to: A N Martinez, Francis J Curry National Tuberculosis Center, 3180 18th Street, Suite 102, San Fran- cisco, CA 94110, USA. Tel: (+415) 502-5412. Fax: (+415) 502-7561. Article submitted 10 December 1998. Final version accepted 7 September 1999.