Of the 7 women with culture-confirmed pulmonary TB, 3 had a positive symptom screen and 3 were Xpert positive (Fig. 2). Two women with culture-confirmed pulmonary TB were both positive by WHO TB symptom screen and Xpert. One woman with a positive AFB smear had TB symptoms (cough and night sweats); 2 women with a positive LAM had TB symptoms (one reported fever and night sweats, and one reported cough and night sweats). None of the smear or LAM-positive women had positive TB sputum cultures. Women with positive smear microscopy or M. tuberculosis sputum culture were prescribed anti-TB therapy by the TB program.
In terms of overall performance of a single screen or test as measured by AUC, report of household symptoms (AUC 0.70, 95% CI: 0.50 to 0.90), Xpert (AUC 0.71, 95% CI: 0.51 to 0.91), and TST (AUC 0.78, 95% CI: 0.53 to 1.0) performed similarly (Table 2) for pulmonary TB in this study. Using TST and Xpert yielded the highest combination of sensitivity and specificity (AUC 0.90, 95% CI: 0.86 to 0.95).
Intensified TB case finding using the WHO 4-part symptom screen of fever, cough, night sweats, or weight loss among pregnant women failed to identify more than half [4 of 7 (57%)] of the cases of culture-confirmed pulmonary TB. Low sensitivity of the WHO symptom screen (28%–50%) for excluding TB has been observed in other studies of pregnant HIV-infected women that performed sputum culture independent of clinical symptoms.10,11,25 An individual participant data meta-analysis that included cohorts of HIV-infected cART-naive individuals from sub-Saharan Africa and Southeast Asia found that the sensitivity of the WHO TB symptom screen was 79% overall, and higher among individuals not previously screened for TB (88%).12 The sensitivity of the WHO symptom screen may be decreased in the context of cART and was approximately 50% less sensitive among participants taking cART compared with cART-naive individuals in 2 South African studies.31,32 TB symptoms may be less frequent among women compared with men,33 and pregnancy may further mask symptoms due to an overlap with pregnancy-related physiological changes34 or relative suppression of Th1 proinflammatory cytokines.1,35 We did not screen for malnutrition, which may have impacted weight loss as a TB-screening symptom in our cohort. However, there is no clear consensus on the most appropriate measure of malnutrition in pregnant women, in general, or in HIV-infected pregnant women.36 TB symptom screening in pregnancy may require the addition of other symptoms such as fatigue or inappropriately low weight gain in pregnancy. Despite low sensitivity, prolonged cough was associated with pulmonary TB in our cohort, which has also been observed in pregnant women with TB disease in Tanzania.37
Recent efforts have yielded promising results in developing TB diagnostics in high burden settings,45,46 including those that may perform well specifically in HIV-infected pregnant women47 and point-of-care tests48 that may contribute to TB screening in HIV-infected individuals. Our results highlight the urgent need for improved TB diagnostics for use in HIV-infected pregnant women that have been rigorously evaluated in this vulnerable population.49
Our study had several limitations. We may have underestimated the burden of pulmonary TB by performing culture on a single sputum in 28% of patients. Subjects unable to spontaneously expectorate sputum did not undergo sputum induction, which may have resulted in further underdiagnosis of TB. We did not perform chest radiographs in subjects and may have missed radiographically apparent cases of TB. Xpert testing was performed on only one of 2 sputum samples; for one positive culture from the second sputum culture, Xpert was performed on a cryopreserved sputum sample to ensure adequate estimation of sensitivity. Our study had limited power for estimates of diagnostic performance. Strength of our study is the performance of diagnostic tests, including culture, in all participants regardless of symptoms.
The authors thank the staff at the Ahero Subdistrict Hospital and Bondo District Hospital antenatal clinics, KEMRI/CDC laboratory personnel, and also our study staff and participants.
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