The Bill and Melinda Gates Foundation supports an ambitious portfolio of novel vaccines, drug regimens, and diagnostic tools for tuberculosis (TB). We elicited the expected efficacies and improvements of the novel interventions in discussions with the foundations managing their development. Using an age-structured mathematical model of TB, we explored the potential benefits of novel interventions under development and those not yet in the portfolio, focusing on the WHO Southeast Asia region. Neonatal vaccination with the portfolio vaccine decreases TB incidence by 39% to 52% by 2050. Drug regimens that shorten treatment duration and are efficacious against drug-resistant strains reduce incidence by 10 -27%. New diagnostics reduce incidence by 13-42%. A triple combination of a portfolio vaccine, drug regimen, and diagnostics reduces incidence by 71%. A short mass vaccination catch-up campaign, not yet in the portfolio, to augment the triple combination, accelerates the decrease, preventing >30% more cases by 2050 than just the triple combination. New vaccines and drug regimens targeted at the vast reservoir of latently infected people, not in the portfolio, would reduce incidence by 37% and 82%, respectively. The combination of preventive latent therapy and a 2-month drug treatment regimen reduces incidence by 94%. Novel technologies in the pipeline would achieve substantial reductions in TB incidence, but not the Stop TB Partnership target for elimination. Elimination will require new delivery strategies, such as mass vaccination campaigns, and new products targeted at latently infected people. latent infection ͉ novel interventions ͉ transmission model ͉ latent therapy T he Bill and Melinda Gates Foundation (BMGF) supports an ambitious portfolio of novel vaccines, treatment regimens, and diagnostic tools for tuberculosis (TB). Funded by BMFG and other sources, the Aeras Global TB Vaccine Foundation oversees vaccine development (1), the TB Alliance seeks novel drug regimens (2), and the Foundation for Innovative New Diagnostics (FIND) looks for new diagnostic tools (3). The current cornerstone of TB intervention is directly observed short-course therapy (DOTS), lasting generally 6 months and prone to dropout (4). DOTS is currently implemented in the 184 countries where 99% of all estimated TB cases occurred and 93% of the world population lived in 2006 (5). Cases are passively ascertained. Sputum smear light microscopy has been the mainstay of TB diagnosis for more than a century, but has important limitations (3). Delays between the patient visit to the clinic and diagnosis often lead to delays in treatment. Neonatal vaccination with bacillus Calmette-Guérin (BCG) vaccine is part of the expanded program of immunization in many countries, but its efficacy against pulmonary TB is poor (1). Despite these efforts, in large parts of Asia, Africa, Eastern Europe, and Latin America, incidence remains 2 orders of magnitude (5) above the Stop TB Partnership goal to eliminate TB as a public health problem, defined as Ͻ1 ...

Previous studies of postpartum amenorrhea (PPA) demonstrated distinct subgroups of women with short and long durations of amenorrhea. This phenomenon was attributed to cases where breastfeeding is absent because of pregnancy loss or infant death, or confusion of postpartum bleeding with resumption of menses. We explored these ideas using data from an 11-month prospective study in Bangladesh in which 858 women provided twice-weekly interviews and urine specimens for up to 9 months; 300 women were observed while experiencing PPA. The resulting exact, interval-censored, or right-censored durations were used to estimate parameters of two-component mixture models. A mixture of two Weibull distributions provided the best fit to the observations. The long-duration subgroup made up 84% (+/- 4% SE) of the population, with a mean duration of 457 (+/- 31) days. The short-duration subgroup had a mean duration of 94 (+/- 17) days. Three covariates were associated with the duration of PPA: women whose husbands had high-wage employment had a greater probability of falling in the short-duration subgroup; women in the long-duration subgroup whose husbands seasonally migrated had shorter periods of PPA within the subgroup; and mothers in the short-duration subgroup who gave birth during the monsoon season experienced a shortened duration of PPA within the subgroup. We conclude that the bimodal distribution of PPA reflects biological or behavioral heterogeneity rather than shortcomings of data collection.