Tuberculosis among adults starting antiretroviral therapy in South Africa: The need for routine case finding
To investigate the prevalence of and evaluate screening modalities for undiagnosed tuberculosis (TB) in antiretroviral therapy (ART) eligible adults in South Africa.
Individuals were screened for TB using symptoms, chest radiograph (CXR) and two sputum specimens for microscopy and culture, and were then followed for <6 months to determine TB diagnoses.
Among 361 participants (67% female, median age 38 years, median CD4 count 120 cells/mm(3)), 64 (18%) were sputum culture-positive; 114 (32%) fulfilled any TB case definition (culture- and/or smear-positive, or improvement on specific treatment). Symptom screening comprising any of cough, appetite loss or night sweats > 2 weeks had a sensitivity and specificity of respectively 74.5% and 50.8%. Sensitivity was increased by CXR (to 96.1%), but not by smear microscopy. The World Health Organization symptom screen had a sensitivity and specificity of respectively 96.1% and 5.2% in our study population; the addition of CXR increased sensitivity to 100%. Median time to TB treatment was 8 days for diagnoses based on CXR (n = 72) vs. 37 days for diagnoses based only on sputum culture (n = 14).
The very high prevalence of undiagnosed TB among patients presenting for ART mandates their routine investigation. CXR improved sensitivity substantially, allowed rapid treatment initiation and should be routine, where available, pending better point-of-care diagnostics.
Available from: PubMed Central
- "Others are used on initially sputum smear-negative (SN) patients to improve and accelerate diagnosis of PTB (32–34). Few have tried to combine signs and symptoms into a CPR to screen for PTB (35–38) and only two CPRs to monitor TB treatment response have been proposed (16, 39). Horita et al. (39) suggest a score consisting of age (in years), oxygen requirement, albumin concentration (g/dl), and activity of daily living. "
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ABSTRACT: Background : The tuberculosis (TB) case detection rate has stagnated at 60% due to disorganized case finding and insensitivity of sputum smear microscopy. Of the identified TB cases, 4% die while being treated, monitored with tools that insufficiently predict failure/mortality. Objective : To explore the TBscore, a recently proposed clinical severity measure for pulmonary TB (PTB) patients, and to refine, validate, and investigate its place in case finding. Design : The TBscore's inter-observer agreement was assessed and compared to the Karnofsky Performance Score (KPS) (paper I). The TBscore's variables underlying constructs were assessed, sorting out unrelated items, proposing a more easily assessable TBscoreII, which was validated internally and externally (paper II). Finally, TBscore and TBscoreII's place in PTB-screening was examined in paper III. Results : The inter-observer variability when grading PTB patients into severity classes was moderate for both TBscore (κ W=0.52, 95% CI 0.46-0.56) and KPS (κ W=0.49, 95% CI 0.33-0.65). KPS was influenced by HIV status, whereas TBscore was unaffected by it. In paper II, proposed TBscoreII was validated internally, in Guinea-Bissau, and externally, in Ethiopia. In both settings, a failure to bring down the score by ≥25% from baseline to 2 months of treatment predicted subsequent failure (p=0.007). Finally, in paper III, TBscore and TBscoreII were assessed in health-care-seeking adults and found to be higher in PTB-diagnosed patients, 4.9 (95% CI 4.6-5.2) and 3.9 (95% CI 3.8-4.0), respectively, versus patients not diagnosed with PTB, 3.0 (95% CI 2.7-3.2) and 2.4 (95% CI 2.3-2.5), respectively. Had we referred only patients with cough >2 weeks to sputum smear, we would have missed 32.1% of the smear confirmed cases in our cohort. A TBscoreII>=2 missed 8.6%. Conclusions : TBscore and TBscoreII are useful monitoring tools for PTB patients on treatment, as they could fill the void which currently exists in risk grading of patients. They may also have a role in PTB screening; however, this requires our findings to be repeated elsewhere.
Available from: Joanna d'Arc Lyra Batista
- "In developing countries, the diagnosis of pulmonary TB is heavily dependent on AFB sputum smear microscopy, which has low sensitivity among PLHIV , who often present extra pulmonary or sputum smear-negative pulmonary TB, resulting in late diagnosis  and therefore either delayed or no treatment . This has led to the suggestion that empirical treatment of tuberculosis (i.e. "
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ABSTRACT: Tuberculosis (TB) is the leading cause of death related to HIV worldwide. This study analyzes the survival of People Living with HIV (PLHIV) reporting cough without bacteriological confirmation of TB and identify factors associated with death.
Prospective cohort with a consecutive sample of PLHIV, aged >= 18 years. Patient inclusion criteria were complaint of current cough of any duration at the time of the first study interview or during their subsequent routine visits to health services and for whom AFB sputum smear was either negative or not performed during the whole follow-up period. Kaplan-Meier method was used to calculate the probability of survival. We estimated the Hazard Ratio (HR) in bivariate and multivariate Cox regression analyses.
Mortality was 4.6 per 100 py; 73% were receiving HAART at recruitment. Average time from the first recorded date of cough until empirical treatment for tuberculosis was six months. Mortality was higher when the CD4 count was low (HR = 5.3; CI 95%: 3.2-9.0; p = 0.000), in those with anemia (HR = 3.0; CI 95%: 1.6-5.6; p = 0.001) and with abnormal chest X-rays (HR = 2.4; CI 95%: 1.4-4.0; p = 0.001). Mortality was higher in those receiving empirical TB treatment (HR = 2.4; CI 95%: 1.4-4.0; p = 0.002), but only in those with normal X-rays, no history of tuberculosis and no bacteriology requests. Empirical treatment for TB was more frequent in PLHIV with low CD4 counts, anemia, history of opportunistic infections, weight loss, previous tuberculosis, negative bacteriology test (as opposed to not having a test) and abnormal chest X-ray.
Higher mortality in PLHIV reporting a current cough without bacteriological confirmation of tuberculosis was identified for those with a CD4 cell count <200, abnormal chest X-ray, anemia and empirical treatment for tuberculosis. Mortality was not significantly higher in those empirically treated for TB, who had three characteristics suggestive of the disease (abnormal chest X-ray, history of TB treatment, AFB sputum smear or M.tb culture testing). Routine cohorts are not an adequate setting to evaluate the impact of empirical treatment for TB on the mortality of PLHIV.
Available from: Catriona John Waitt
- "Sputum smear microscopy and culture are established diagnostic standards , with chest X-ray (CXR) being called into question due to limited diagnostic accuracy and poor film quality, particularly in low-resource settings. Despite these limitations, many diagnostic algorithms still include CXR [2–5]. Furthermore, in resource-poor settings, where the majority of TB patients are diagnosed, infrastructure is often erratic and unreliable . "
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ABSTRACT: OBJECTIVES: In low-resource settings, limitations in diagnostic accuracy of chest X-rays (CXR) for pulmonary tuberculosis (PTB) relate partly to non-expert interpretation. We piloted a TB CXR Image Reference Set (TIRS) to improve non-expert performance in an operational setting in Malawi. METHODS: Nineteen doctors and clinical officers read 60 CXR of patients with suspected PTB, at baseline and using TIRS. Two officers also used the CXR Reading and Recording System (CRRS). Correct treatment decisions were assessed against a "gold standard" of mycobacterial culture and expert performance. RESULTS: TIRS significantly increased overall non-expert sensitivity from 67.6 (SD 14.9) to 75.5 (SD 11.1, P = 0.013), approaching expert values of 84.2 (SD 5.2). Among doctors, correct decisions increased from 60.7 % (SD 7.9) to 67.1 % (SD 8.0, P = 0.054). Clinical officers increased in sensitivity from 68.0 % (SD 15) to 77.4 % (SD 10.7, P = 0.056), but decreased in specificity from 55.0 % (SD 23.9) to 40.8 % (SD 10.4, P = 0.049). Two officers made correct treatment decisions with TIRS in 62.7 %. CRRS training increased this to 67.8 %. CONCLUSION: Use of a CXR image reference set increased correct decisions by doctors to treat PTB. This tool may provide a low-cost intervention improving non-expert performance, translating into improved clinical care. Further evaluation is warranted. KEY POINTS : • Tuberculosis treatment decisions are influenced by CXR findings, despite improved laboratory diagnostics. • In low-resource settings, CXR interpretation is performed largely by non-experts. • We piloted the effect of a simple reference training set of CXRs. • Use of the reference set increased the number of correct treatment decisions. This effect was more marked for doctors than clinical officers. • Further evaluation of this simple training tool is warranted.
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