TB in mothers increases risk of HIV passing to babies

Maternal tuberculosis (TB) increased the risk of mother-to-child HIV transmission 2.5 fold, Amita Gupta and colleagues reported in a study published in the February 1st edition of the Journal of Infectious Diseases.

The authors undertook an analysis of data from 783 mother-infant pairs enrolled in a prospective, randomized, placebo-controlled six week extended dose nevirapine prophylaxis trial (SWEN) (includes 41 pairs in an ancillary cohort) from August 2002 to September 2007 in a large, urban public teaching hospital in India.

TB is recognised as the leading infectious cause of death among women worldwide and the most important cause of disease and death among women with HIV in resource-poor settings. Women account for approximately 70% of all HIV infections where heterosexual transmission is dominant. The highest number of HIV and TB infections occurs in women of child-bearing age (15-49 years). TB and HIV-TB co-infection during pregnancy and after birth often result in infant and maternal disease and death.

In an accompanying editorial Dr Ben Marais, a specialist in child health at Stellenbosch University, South Africa, notes that while it is generally recognised that people with HIV are at greater risk for TB infection, the role that TB plays in HIV transmission and disease progression is not fully appreciated.

Established independent risk factors for mother-to-child HIV transmission include maternal viral load, CD4 cell count, length of breastfeeding, antiretroviral treatment and malaria co-infection.

The purpose of the analysis of TB and HIV transmission within the SWEN study was to determine the effect of maternal TB on the risks of vertical HIV transmission from mother to child.

The primary goal of the SWEN study was to compare extended nevirapine versus single-dose nevirapine to reduce vertical HIV transmission among breastfed infants. The authors assessed the effect of maternal TB on the risk of vertical transmission during pregnancy and in the 12 months after delivery.

Among the 783 mothers 33 had TB: three prevalent (or TB diagnosed before entering the study) and 30 incident (or a new TB diagnosis during follow-up).  Of the 33, 10 (30%) transmitted HIV to their infants compared to 87 out of a total of 750 mothers without TB (12%). (Odds ratio 2.51, CI: 95% 1.05-6.02; P= 0.04)

Marais points out that the numbers with incident TB (30 out of 780) translates to a TB incidence rate of 3846 cases/100,000 population/year, which he notes is exceptionally high.

Although the authors do not speculate on the reasons for this high incidence rate,  there is some evidence in the study population to suggest that late diagnosis of TB was a problem among women in the trial, implying the potential for considerable transmission of TB within health care facilities attended by women taking part in the trial.

The authors suggest reasons why maternal TB might be associated with MTCT in a breastfeeding population. Maternal TB may increase maternal HIV infectiousness through an increase in viral load; an increase in viral load in breast-milk and; in the same way that studies have shown placental malaria and sexually-transmitted infections increase transmission by the mechanism of immune activation and infectiousness.

Marais notes increased viral load because of immune stimulation in mothers with TB accounted for much of the increased risk. However, he points out as do the authors that the increased risk remained after multivariate analysis corrected for maternal (viral load, CD4 cell count, antiretroviral use) and infant factors (nevirapine administration and breastfeeding duration).

 The authors stress that while maternal TB was associated with a small fraction of MTCT it is preventable with what is referred to as the 3 I’s, a TB control strategy recommended by the World Health Organization (WHO): improved infection control, improved community-based intensive case-finding, and implementation of isoniazid prevention therapy.

This study showed that maternal TB was independently associated with an increased risk of MTCT in women who breastfed and had a TB diagnosis less than six months after delivery.

Marais notes that most of the infants were diagnosed with HIV at delivery (suggesting transmission during pregnancy) and very close to maternal TB diagnosis. He stresses that not only has the study shown an association between maternal TB and infant HIV diagnosis but the clustering of these two events suggests a causal relationship.  

Limitations include, according to the authors, the analysis is a secondary endpoint of the clinical trial which was not originally designed to test the hypothesis of maternal TB as a risk factor for mother to child transmission; not all TB diagnoses were culture-confirmed.

Marais underscores that the very high TB disease and transmission risk “provides additional motivation to carefully monitor all HIV-infected women for TB during and after pregnancy.”

Marais concludes “renewed global focus on maternal and child health…is welcomed…but adequate recognition must be given to the importance of TB control and prevention in areas where TB is endemic.”