TB in HIV-positive Indian mothers doubles risk of maternal and infant death

Postpartum tuberculosis (TB) in HIV-infected pregnant women is associated with a high incidence of maternal and infant deaths, according to the findings of a prospective study in India, published in the July 15^th issue of Clinical Infectious Diseases. The study's authors call for active screening and targeted use of isoniazid preventative therapy among HIV-infected women in India as an urgent control measure for postpartum TB.

HIV and TB are independently important risk factors for maternal mortality and adverse perinatal outcomes. During the current HIV era, maternal mortality due to TB has more than doubled compared to that during the pre-HIV era. In Durban, South Africa, the rate of TB disease in HIV-1-infected pregnant women was about ten times higher than that among HIV-uninfected pregnant women.

Maternal TB increases the risk of mother-to-child transmission of TB through several routes. Neonatal TB is attributed to delayed diagnosis of maternal TB and lack of treatment. In a South African study, mother-to child-transmission of TB was observed in 15 % of infants born to a study cohort of pregnant women in which 77 % were HIV-1-infected. TB in infants, whether acquired in the womb, during delivery or after birth, is associated with high mortality rates. Maternal HIV/TB coinfection also increases the risk of mother-to child transmission of HIV.

Maternal HIV/TB coinfection therefore exerts an enormous toll on fragile public health systems in poor countries due to the ravages of both diseases on maternal and infant health. In India, the country with the highest TB burden globally, isoniazid preventative therapy (IPT) is not recommended for HIV-1-infected persons with latent TB. This is out of concern about the risk of increasing the community burden of isoniazid-resistant TB infection.

Delivery and the postpartum period represent important entry points into the public health systems for instituting TB prevention and management. In the absence of IPT in India, there was a need to determine the incidence of active TB in postpartum Indian women and to determine the effect of maternal HIV/TB coinfection on maternal and infant health. The study was undertaken by a team of Indian and US investigators.

The study was carried out from August 2002 to December 2005 as part of a Phase III trial to assess the role of nevirapine therapy in breastfed infants at a public hospital in Pune, India. Seven hundred fifteen HIV-infected mothers and their infants were prospectively followed up for one year after delivery. Women were evaluated for active TB during regular clinic visits, and tuberculin skin tests were performed.

Twenty-four of 715 HIV-infected women who were followed up for 480 postpartum person-years developed TB. This yielded a TB incidence of five cases per 100 person-years (95% confidence interval [CI], 3.2–7.4 cases per 100 person-years). Compared with women who were not infected, women with incident TB were more likely to be unemployed and to have a lower median baseline CD4 cell count, a higher median HIV load, positive tuberculin skin testing (TST) results and moderate anemia.

Predictors of incident TB included a baseline CD4 cell count less than 200 cells/mm³ (adjusted incident rate ratio [IRR], 7.58; 95% CI, 3.07–18.71), an HIV viral load higher than 150,000 copies/ml (adjusted IRR, 3.92; 95% CI, 1.69–9.11), and a positive tuberculin skin test result (adjusted IRR, 3.08; 95% CI, 1.27–7.47). Three (12.5%) of 24 women with TB died, compared with seven (1%) of 691 women without TB (IRR, 12.2; 95% CI, 2.03–53.33).

Among 23 viable infants with mothers with TB, two received a diagnosis of TB. Four infants with mothers with TB died, compared with 28 infants with mothers without TB (IRR, 4.71; 95% CI, 1.19–13.57). Infants whose mothers had incident TB were more likely to have HIV infection by one year of age than were infants whose mothers did not have incident TB.

Women with incident TB and their infants had a 2.2- and 3.4-fold increased probability of death, respectively, compared with women without active TB and their infants, controlling for factors independently associated with mortality (adjusted IRR, 2.2 [95% CI, 0.6–3.8] and 3.4 [95% CI, 1.22–10.59], respectively).

The study found a high incidence of postpartum TB and associated postpartum maternal and infant death among Indian HIV-infected women. The policy implication is that active screening and targeted use of isoniazid preventative therapy among HIV-infected women in India should be implemented to prevent postpartum maternal TB and associated mother-to-child morbidity and mortality.

In an accompanying editorial, Lynn Mofenson of the US National Institutes of Health and Barbara Laughon of the US National Institute of Allergy and Infectious Disease recommend screening for TB and HIV at antenatal clinics as well as prevention, diagnosis, and treatment of TB in all regions with a high burden of TB/HIV coinfection. The urgent implementation of this strategy will help to reduce maternal mortality in resource-poor countries, they say.