Pregnancy-Related Tuberculous Meningitis and Immune Reconstitution Inflammatory Syndrome: A Case Series and Systematic Review

Abstract

Background Tuberculosis is a leading cause of death among women of reproductive age. However, tuberculous meningitis, the most severe form of extrapulmonary tuberculosis, is rarely discussed in pregnancy despite this being a unique period of immune modulation which may predispose women to active disease. Methods We identified and described cases of tuberculous meningitis among pregnant or postpartum women screened during meningitis clinical trials in Uganda from 2018-2022. We conducted a systematic literature review via PubMED/MEDLINE and EMBASE for all English language publications from 1970 to July 10, 2022, to identify additional cases. Results We identified 8 cases of pregnancy-related tuberculous meningitis in Ugandan women living with HIV and 40 additional cases via systematic literature review (none HIV-positive). Of all combined cases, 50% (24/48) were diagnosed postpartum; 50% (24/48) had initial onset during pregnancy, of which 38% (9/24) had worsening of symptoms or disease relapse following pregnancy cessation. Diagnosis was missed or delayed in 33% (16/48) of cases. For those with known outcomes, maternal mortality was 23% (11/48) and fetal/neonatal mortality was 30% (13/44). Of maternal survivors, 30% (11/37) had residual neurologic deficits. Conclusion The true incidence of tuberculous meningitis in pregnancy or the postpartum period is unclear but likely underappreciated. To date, nearly all published cases have occurred in HIV-negative, or otherwise immunocompetent women. Given the well-described physiological immunosuppression during pregnancy and subsequent reconstitution postpartum, physicians must be aware of tuberculous meningitis and pregnancy-related immune reconstitution inflammatory syndrome, especially in high burden tuberculosis countries and in women living with HIV.