Intensive Tuberculosis Screening for HIV‐Infected Patients Starting Antiretroviral Therapy in Durban, South Africa

Abstract

Background The World Health Organization (WHO) recommends cough as the trigger for tuberculosis (TB) screening in HIV-infected patients, with acid fast bacillus (AFB) smear as the initial diagnostic test. Our objective was to assess the yield and cost of a more intensive TB screening in HIV-infected patients starting antiretroviral therapy (ART) in Durban, South Africa. Methods We prospectively enrolled adults, regardless of TB signs/symptoms, undergoing pre-ART training from May ‘07–May ‘08. Following symptom screen, patients expectorated sputum for AFB smear, TB polymerase chain reaction (PCR), and mycobacterial culture. Sensitivity and specificity of different symptoms and tests, alone and in combination, were compared to a gold standard of 6-week TB culture results. Program costs included personnel, materials and cultures. Results Of 1,035 subjects, 487 (59%) were female; median CD4 count was 100/μl. Two-hundred and ten (20%) were receiving TB treatment and were excluded. Of the remaining 825 subjects, 158 (19%) had positive sputum cultures, of whom 14 (9%) had a positive AFB smear and 82 (52%) reported cough. The combination of cough, other symptoms, AFB smear, and chest x-ray had 93% (CI 88–97%) sensitivity and 15% (CI 13–18%) specificity. The incremental cost of intensive screening including culture was $360/additional TB case identified. Conclusions Nearly 20% of patients starting ART in Durban, South Africa had undiagnosed, culture-positive pulmonary TB. Despite WHO recommendations, neither cough nor AFB smear were adequately sensitive for screening. TB sputum cultures should be performed before ART initiation, regardless of symptoms, in areas of high HIV/TB prevalence.

Tuberculosis among adults starting antiretroviral therapy in South Africa: the need for routine case finding

“…Screening for this group requires high sensitivity to avoid missing cases, but in a resource-constrained setting, this must be balanced against the high costs resulting from a test combination with poor specificity. We found sputum microscopy had very poor sensitivity, consistent with other studies, 16,19,[23][24][25] as Xpert MTB/RIF 27 at US$17 per cartridge, 28 the cost to health services may be substantial, and the cost-effectiveness of a range of algorithms for different settings needs to be investigated. 90% of our culture-proven tuberculosis cases were smearnegative, and Xpert MTB/RIF has reported sensitivities from 43%-73% for smearnegative culture-positive tuberculosis from a single sputum sample.…”

“…In high prevalence settings systematic sputum culture for all patients prior to ART has also been suggested, but presents the same challenges of access. 12,16 In our study, most culture-positive patients started tuberculosis treatment based on clinical and radiological features prior to availability of culture results; even with liquid culture, the median time to tuberculosis treatment start based on a positive culture was 37 days.…”

“…Our prevalence is similar to recent data from Western Cape (32%), 12 but higher than generally reported among ART-eligible adults in Africa (3%-19%). 10,11,16,[18][19][20] This reflects systematic screening of our patients using multiple modalities, and a broad case definition allowing diagnosis based on radiological and clinical features highlighting the 'real life' burden, and recognising that sputum culture misses some cases of disseminated tuberculosis. 21 Our 18% prevalence of cultureconfirmed pulmonary tuberculosis accords with studies from Cambodia (17%), 22 KwaZulu-Natal (19%), 16 and Western Cape (17%).…”

The diagnostic gap: Characterising the profile of undiagnosed infectious tuberculosis patients in the community

“…[14] For example, a study from Durban, SA, found that up to 22% of patients screened with sputum cultures prior to entering an ART programme had asymptomatic or subclinical TB. [23] However, despite modifying our screening protocol to include all HIV-infected patients regardless of symptoms, we did not find any subclinical or asymptomatic TB among HIV-infected patients participating in our study. This finding is likely to be influenced in part by a selection bias, as HIV-positive individuals in the community were not screened in a systematic way.…”

Training Laboratory Technicians from the Ethiopian Periphery in the MODS Technique Enables Rapid and Low-Cost Diagnosis of Mycobacterium tuberculosis Infection

“…13 Consequently, this method fails to identify about 25-50% of the patients with TB, [14][15][16][17] and is even less sensitive in HIVpositive patients (9-57%). 17,18 More sensitive methods for diagnosis of TB are polymerase chain reaction (PCR) of the sputum, cultures on solid media (Lowenstein-Jensen or Middlebrook formulations), and liquid media. 13 The main disadvantages of these methods are their high cost (e.g., commercial PCR systems and liquid culture in automated systems) and the long duration of incubation needed to obtain positive culture and drug susceptibility results (culture on solid media), which make these techniques unsuitable for use in remote third world regions.…”