Haileyesus Getahun and colleagues report the development of a simple, standardized tuberculosis (TB) screening rule for resource-constrained settings, to identify people living with HIV who need further investigation for TB disease.

OBJECTIVE-To determine whether interferon-gamma release assays (IGRAs) improve the identification of HIV-infected individuals who could benefit from LTBI therapy. DESIGN-Systematic review and meta-analysis.METHODS-We searched multiple databases through May2010 for studies evaluating the performance of the newest commercial IGRAs (QuantiFERON-Gold In-tube [QFT-GIT] and T-SPOT. TB [TSPOT])in HIV-infected individuals. We assessed the quality of all studies included in the review, summarized results in pre-specified sub-groups using forest plots, and where appropriate, calculated pooled estimates using random effects models. RESULTS-The search identified 37 studies that included 5736 HIV-infected individuals. In3 longitudinal studies, the risk of active TB was higher in HIV-infected individuals with positive versus negative IGRA results. However, the risk difference was not statistically significant in the 2 studies that reported IGRA results according to manufacturer-recommended criteria. In persons with active TB(a surrogate reference standard for LTBI), pooled sensitivity estimates were heterogeneous, but higher for TSPOT (72%, 95% CI 62-81%) than for QFT-GIT (61%, 95% CI 41-75%). However, neither IGRA was consistently more sensitive than the tuberculin skin test (TST) in head-to-head comparisons. While TSPOT appeared to be less affected by immunosuppression than QFT-GIT and TST, overall, differences between the three tests were small or inconclusive.CONCLUSIONS-Current evidence suggests that IGRAs perform similarly to the TST at identifying HIV-infected individuals with LTBI. Given that both tests have modest predictive value and sub-optimal sensitivity, the decision to use either test should be based on country guidelines and resource and logistical considerations.

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BackgroundMultidrug resistant and extensively drug resistant tuberculosis (TB) have become major threats to control of tuberculosis globally. The rates of anti-TB drug resistance in Uganda are not known. We conducted a national drug resistance survey to investigate the levels and patterns of resistance to first and second line anti-TB drugs among new and previously treated sputum smear-positive TB cases.MethodsSputum samples were collected from a nationally representative sample of new and previously treated sputum smear-positive TB patients registered at TB diagnostic centers during December 2009 to February 2011 using a weighted cluster sampling method. Culture and drug susceptibility testing was performed at the national TB reference laboratory.ResultsA total of 1537 patients (1397 new and 140 previously treated) were enrolled in the survey from 44 health facilities. HIV test result and complete drug susceptibility testing (DST) results were available for 1524 (96.8%) and 1325 (85.9%) patients, respectively. Of the 1209 isolates from new cases, resistance to any anti-TB drug was 10.3%, 5% were resistant to isoniazid, 1.9% to rifampicin, and 1.4% were multi drug resistant. Among the 116 isolates from previously treated cases, the prevalence of resistance was 25.9%, 23.3%, 12.1% and 12.1% respectively. Of the 1524 patients who had HIV testing 469 (30.7%) tested positive. There was no association between anti-TB drug resistance (including MDR) and HIV infection.ConclusionThe prevalence of anti-TB drug resistance among new patients in Uganda is low relative to WHO estimates. The higher levels of MDR-TB (12.1%) and resistance to any drug (25.3%) among previously treated patients raises concerns about the quality of directly observed therapy (DOT) and adherence to treatment. This calls for strengthening existing TB control measures, especially DOT, routine DST among the previously treated TB patients or periodic drug resistance surveys, to prevent and monitor development and transmission of drug resistant TB.

Objective 1. To assess inter-and intra-observer variation in the histopathological reporting of cervical colposcopic biopsies using a histologic modification of the cytological Bethesda grading system; 2. to determine the histologic profile of those cases which resulted in diagnostic disagreement.Methods Consecutive cervical colposcopic biopsies (n = 125) were assessed independently by six experienced histopathologists. Cases were classified as normal, low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion. Six months later the process was repeated. The degree of inter and intra-observer variation was assessed by kappa statistics. All cases in which there was less than perfect inter and intra-observer agreement were reviewed by the coordinator of the study. ResultsIn the first round of the study inter-observer agreement was generally poor, with unweighted and weighted kappa values ranging from 0.15 to 0.58 (average 0.30) and from 0.21 to 0.61 (average 0.36) respectively. In the second round inter-observer agreement was better, with unweighted and weighted kappa values ranging from 0.08 to 0.55 (average 0-33) and from 0.22 to 0.59 (average 0.42). Ten of the 15 pairs of observers achieved fair inter-observer agreement using weighted kappa analysis. The degree of intra-observer agreement was better, unweighted and weighted kappa values ranging from 0.26 to 0.61 (average 0.47) and from 0.34 to 0.62 (average 0-51) respectively. Two of the six participants achieved fair intra-observer agreement and two achieved good intra-observer agreement using weighted kappa analysis. There were marked difficulties in the separation of normal squamous epithelium from low grade squamous intraepithelial lesion and in the separation of low grade from high grade squamous intraepithelial lesions. Histopathological review revealed that many of the difficulties in the separation of normal and low grade squamous intraepithelial lesion were in the distinction between superficial vacuolated cells and true koilocytes. Difficulties also resulted in the separation of basal cell hyperplasia, inflammatory associated changes and immature squamous metaplasia from low grade squamous intraepithelial lesion. Conditions which resulted in difficulty in the separation of low grade and high grade squamous intraepithelial lesions included florid koilocytotic change and immature metaplastic squamous epithelium with atypia. In some cases, there was a full spectrum of diagnoses from normal to high grade squamous intraepithelial lesion. These were largely cases of immature metaplastic squamous epithelium with atypia and of thin or atrophic squamous epithelium with atypia.Conclusions Most pairs of observers can achieve fair inter-observer agreement in the reporting of cervical colposcopic biopsies using a modified Bethesda system. Intra-observer agreement is also generally fair to good using this system. It may be that a two tier grading system is more appropriate for the histopathological reporting of these biopsies than the tr...

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Eighty patients with non-insulin-dependent diabetes mellitus being treated in a south Indian hospital were biopsied to confirm suspected nondiabetic renal disease (NDRD). The positive predictive value of the standard clinical indicators for NDRD in the presence or absence of diabetic retinopathy was 54 and 87%, respectively. These values are higher than those given by comparable studies in Western populations. This is probably due to a higher prevalence of NDRD in the population of south India, and especially of proliferative glomerulonephritis, which was found in 21.5% of the patients studied. Standard clinical predictors of NDRD in diabetics have a high predictive value in the tropics where there is a high prevalence of proliferative glomerulonephritis.