Latent Tuberculosis Detection by Interferon γ Release Assay during Pregnancy Predicts Active Tuberculosis and Mortality in Human Immunodeficiency Virus Type 1–Infected Women and Their Children

Abstract

Background We evaluated the prognostic utility of interferon-gamma release assays (IGRAs) for active tuberculosis (TB) and mortality in Kenyan HIV-1 infected women and their infants. Methods Prevalence and correlates of Mycobacterium tuberculosis-specific T-SPOT.TB IGRA positivity were determined during pregnancy in a historical cohort of HIV-1 infected women. Hazard ratios, adjusted for baseline maternal CD4 count (aHRCD4) were calculated for associations between IGRA positivity and risk of active TB and mortality over 2-year postpartum follow-up in women and their infants. Results Of 333 women tested, 52 (15.6%) had indeterminate IGRAs. Of the remaining 281 women, 120 (42.7%) had positive IGRAs, which were associated with a 4.5-fold increased risk of active TB [aHRCD4: 4.5; 95% confidence interval (CI): 1.1–18.0; p=0.03]. Among immunosuppresed women (CD4<250 cell/mm3), positive IGRAs were associated with increased risk of maternal mortality (aHRCD4: 3.5; 95% CI: 1.02–12.1; p=0.045), maternal active TB or mortality (aHRCD4: 5.2; 95% CI: 1.7–15.6; p=0.004) and infant active TB or mortality, overall (aHRCD4: 3.0; 95% CI: 1.0–8.9; p= 0.05) and in HIV-1 exposed uninfected infants (aHRCD4: 7.3; 95% CI: 1.6–33.5; p =0.01). Conclusions Positive IGRAs in HIV-1 infected pregnant women were associated with postpartum active TB and mortality in mothers and their infants.

Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

“…Fifteen studies with a combined sample size of 26,680 participants were included in this analysis (107)(108)(109)(110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121). The incidence of active TB during a median follow-up of 3 years was 2 to 24 per 1,000 person-years for IGRA-negative individuals (Fig.…”

“…Three studies specifically assessed the prognostic value of the IGRAs in an exclusively HIV-positive cohort (110,118,125). Two studies without possible incorporation bias (where IGRAs were not used to make a final diagnosis of active TB) and differential work-up bias (where IGRA-positive individuals were not investigated more intensively for active TB than IGRA-negative individuals) (118,125) found risk ratios of 2.69 (95% CI, 0.69 to 10.52) and 3.32 (95% CI, 1.09 to 10.08), respectively, meaning that individuals with a positive IGRA result had around a 3-fold-increased risk of progression to TB disease during the follow-up period of the study compared to individuals with a negative IGRA result.…”

“…Two studies without possible incorporation bias (where IGRAs were not used to make a final diagnosis of active TB) and differential work-up bias (where IGRA-positive individuals were not investigated more intensively for active TB than IGRA-negative individuals) (118,125) found risk ratios of 2.69 (95% CI, 0.69 to 10.52) and 3.32 (95% CI, 1.09 to 10.08), respectively, meaning that individuals with a positive IGRA result had around a 3-fold-increased risk of progression to TB disease during the follow-up period of the study compared to individuals with a negative IGRA result. Although the rate of disease progression after a presumed TB infection is increased in HIV-infected individuals, there are currently no data that suggest that the predictive value of the IGRAs is better or worse in this subpopulation than in others.…”

Tuberculosis and Pregnancy: An Updated Systematic Review

“…Maternal and infant mortality was higher in mothers with a positive IGRA but the difference was not statistically different unless the maternal CD4 count was < 250 cells/mm 3 . 26 Eighteen had a positive test and the number of spot counts was highest at 32 weeks, then fell around delivery, followed by a later increase.…”

“…TB using cryopreserved peripheral blood mononuclear in a cohort of 327 HIV-positive pregnant women in Kenya. 26,27,28 In the first report, 36% of the HIV-infected women were IGRA-positive during pregnancy, which likely reflects the local rate of LTBI. In multivariate analysis, adjusting for baseline CD4 count, IGRA positivity was associated with a 4.5 (1.1-18.0)-fold increased risk of active TB (p=0.03).…”