Development of a Simple Reliable Radiographic Scoring System to Aid the Diagnosis of Pulmonary Tuberculosis

Rationale

Chest radiography is sometimes the only method available for investigating patients with possible pulmonary tuberculosis (PTB) with negative sputum smears. However, interpretation of chest radiographs in this context lacks specificity for PTB, is subjective and is neither standardized nor reproducible. Efforts to improve the interpretation of chest radiography are warranted.

Objectives

To develop a scoring system to aid the diagnosis of PTB, using features recorded with the Chest Radiograph Reading and Recording System (CRRS).

Methods

Chest radiographs of outpatients with possible PTB, recruited over 3 years at clinics in South Africa were read by two independent readers using the CRRS method. Multivariate analysis was used to identify features significantly associated with culture-positive PTB. These were weighted and used to generate a score.

Results

473 patients were included in the analysis. Large upper lobe opacities, cavities, unilateral pleural effusion and adenopathy were significantly associated with PTB, had high inter-reader reliability, and received 2, 2, 1 and 2 points, respectively in the final score. Using a cut-off of 2, scores below this threshold had a high negative predictive value (91.5%, 95%CI 87.1,94.7), but low positive predictive value (49.4%, 95%CI 42.9,55.9). Among the 382 TB suspects with negative sputum smears, 229 patients had scores <2; the score correctly ruled out active PTB in 214 of these patients (NPV 93.4%; 95%CI 89.4,96.3). The score had a suboptimal negative predictive value in HIV-infected patients (NPV 86.4, 95% CI 75,94).

Conclusions

The proposed scoring system is simple, and reliably ruled out active PTB in smear-negative HIV-uninfected patients, thus potentially reducing the need for further tests in high burden settings. Validation studies are now required.     

Impact and Cost-Effectiveness of Culture for Diagnosis of Tuberculosis in HIV-Infected Brazilian Adults

Background

Culture of Mycobacterium tuberculosis currently represents the closest “gold standard” for diagnosis of tuberculosis (TB), but operational data are scant on the impact and cost-effectiveness of TB culture for human immunodeficiency (HIV-) infected individuals in resource-limited settings.

Methodology/Principal Findings

We recorded costs, laboratory results, and dates of initiating TB therapy in a centralized TB culture program for HIV-infected patients in Rio de Janeiro, Brazil, constructing a decision-analysis model to estimate the incremental cost-effectiveness of TB culture from the perspective of a public-sector TB control program. Of 217 TB suspects presenting between January 2006 and March 2008, 33 (15%) had culture-confirmed active tuberculosis; 23 (70%) were smear-negative. Among smear-negative, culture-positive patients, 6 (26%) began TB therapy before culture results were available, 11 (48%) began TB therapy after culture result availability, and 6 (26%) did not begin TB therapy within 180 days of presentation. The cost per negative culture was US$17.52 (solid media)–$23.50 (liquid media). Per 1,000 TB suspects and compared with smear alone, TB culture with solid media would avert an estimated eight TB deaths (95% simulation interval [SI]: 4, 15) and 37 disability-adjusted life years (DALYs) (95% SI: 13, 76), at a cost of $36 (95% SI: $25, $50) per TB suspect or $962 (95% SI: $469, $2642) per DALY averted. Replacing solid media with automated liquid culture would avert one further death (95% SI: −1, 4) and eight DALYs (95% SI: −4, 23) at $2751 per DALY (95% SI: $680, dominated). The cost-effectiveness of TB culture was more sensitive to characteristics of the existing TB diagnostic system than to the accuracy or cost of TB culture.

Conclusions/Significance

TB culture is potentially effective and cost-effective for HIV-positive patients in resource-constrained settings. Reliable transmission of culture results to patients and integration with existing systems are essential.     

Performance of the 2007 WHO Algorithm to Diagnose Smear-Negative Pulmonary Tuberculosis in a HIV Prevalent Setting

Background

The 2007 WHO algorithm for diagnosis of smear-negative pulmonary tuberculosis (PTB) including Mycobacterium tuberculosis (MTB) culture was evaluated in a HIV prevalent area of Kenya.

Methods

PTB smear-negative adult suspects were included in a prospective diagnostic study (2009–2011). In addition, program data (2008–2009) were retrospectively analysed. At the first consultation, clinical examination, chest X-ray, and sputum culture (Thin-Layer-Agar and Lowenstein-Jensen) were performed. Patients not started on TB treatment were clinically re-assessed after antibiotic course. The algorithm performance was calculated using culture as reference standard.

Results

380 patients were included prospectively and 406 analyzed retrospectively. Culture was positive for MTB in 17.5% (61/348) and 21.8% (72/330) of cases. Sensitivity of the clinical-radiological algorithm was 55.0% and 31.9% in the prospective study and the program data analysis, respectively. Specificity, positive and negative predictive values were 72.9%, 29.7% and 88.6% in the prospective study and 79.8%, 30.7% and 80.8% in the program data analysis. Performing culture increased the number of confirmed TB patients started on treatment by 43.3% in the prospective study and by 44.4% in the program data analysis. Median time to treatment of confirmed TB patients was 6 days in the prospective study and 27 days in the retrospective study. Inter-reader agreement for X-ray interpretation between the study clinician and a radiologist was low (Kappa coefficient = 0.11, 95%CI: 0.09–0.12). In a multivariate logistic analysis, past TB history, number of symptoms and signs at the clinical exam were independently associated with risk of overtreatment.

Conclusion

The clinical-radiological algorithm is suboptimal to diagnose smear-negative PTB. Culture increases significantly the proportion of confirmed TB cases started on treatment. Better access to rapid MTB culture and development of new diagnostic tests is necessary.     

Prevalence of Pulmonary Tuberculosis among Adults in a North Indian District

BackgroundRecent population prevalence estimates of pulmonary tuberculosis (PTB) are not available for several areas in India. We conducted a field-based population survey at a north Indian district to estimate point prevalence of bacteriologically positive PTB.MethodsA stratified cluster sampling design was used to conduct the survey in both urban and rural areas within the district. All adults aged more than 15 years, in 18 rural and 12 urban clusters of 3000 subjects each, were interviewed using a symptom card. Two sputum samples were collected from all persons having symptoms suggestive of PTB, or history of antitubercular treatment, for smear microscopy for acid-fast bacilli and mycobacterial culture. Those having at least one sputum specimen positive on microscopy and/or culture were categorized as having PTB. Prevalence was estimated after adjusting for cluster sampling and incomplete data (through individual level analysis with robust standard error).ResultsOf 91,030 eligible adult participants (47,714 men and 43,316 women), 85,770 (94.2%) completed the symptom cards. Of them, 2,898 persons were considered eligible for sputum examination and 2,839 (98.0%) provided at least one sample. Overall, 21 persons had bacteriologically positive PTB, and cluster level prevalence was estimated at 24.5 per 100,000 population (95% CI 12.8–36.2). Individual level analysis with robust standard error yielded a prevalence estimate of 24.1 per 100,000 populations (95% CI 12.8–35.4).ConclusionThe observed prevalence of bacteriologically positive PTB in this district is lower than empiric national estimates, probably as a result of successful implementation of tuberculosis control measures in the area.     

A High Resolution Computer Tomography Scoring System to Predict Culture-Positive Pulmonary Tuberculosis in the Emergency Department

This study evaluated the use of high-resolution computed tomography (HRCT) to predict the presence of culture-positive pulmonary tuberculosis (PTB) in adult patients with pulmonary lesions in the emergency department (ED). The study included a derivation phase and validation phase with a total of 8,245 patients with pulmonary disease. There were 132 patients with culture-positive PTB in the derivation phase and 147 patients with culture-positive PTB in the validation phase. Imaging evaluation of pulmonary lesions included morphology and segmental distribution. The post-test probability ratios between both phases in three prevalence areas were analyzed. In the derivation phase, a multivariate analysis model identified cavitation, consolidation, and clusters/nodules in right or left upper lobe (except anterior segment) and consolidation of the superior segment of the right or left lower lobe as independent positive factors for culture-positive PTB, while consolidation of the right or left lower lobe (except superior segment) were independent negative factors. An ideal cutoff point based on the receiver operating characteristic (ROC) curve analysis was obtained at a score of 1. The sensitivity, specificity, positivity predictive value, and negative predictive value from derivation phase were 98.5% (130/132), 99.7% (3997/4008), 92.2% (130/141), and 99.9% (3997/3999). Based on the predicted positive likelihood ratio value of 328.33 in derivation phase, the post-test probability was observed to be 91.5% in the derivation phase, 92.5% in the validation phase, 94.5% in a high TB prevalence area, 91.0% in a moderate prevalence area, and 76.8% in moderate-to-low prevalence area. Our model using HRCT, which is feasible to perform in the ED, can promptly diagnose culture-positive PTB in moderate and moderate-to-low prevalence areas.     

Characteristics of Patients with Smear-Negative Pulmonary Tuberculosis (TB) in a Region with High TB and HIV Prevalence

Introduction

Smear-negative pulmonary TB (SNPT) represents 30–60% of all pulmonary TB cases. The mortality of these patients can reach 25% in populations with high prevalence of HIV infection, and 10–20% of TB transmission at the population level are attributable to SNPT cases.

Methods

We conducted a retrospective study to evaluate epidemiological, clinical, and radiological characteristics of patients with SNPT and to compare these with patients who were diagnosed as having smear-positive pulmonary TB (SPPT). All adult patients (≥ 18 years old) with a positive culture for Mycobacterium tuberculosis, and a diagnosis of pulmonary TB were included in the study.

Results

198 patients met the inclusion criteria (positive culture for Mycobacterium tuberculosis) and were included in the analysis. Of these patients, 69 (34.8%) were smear positive (SPPT) and 129 (65.2%) were smear negative (SNPT). In univariate analysis, cough, dyspnea, and hemoptysis were less frequent in SNPT patients in comparison with SPPT patients. In a multivariate model, having no cough and no radiographic pattern typical of TB were the characteristics independently associated with a diagnosis of SNPT.

Conclusions

We found a very high prevalence of SNPT among patients with TB in a setting with high TB and HIV prevalence. The absence of cough in the presence of other symptoms suggestive of TB, and having no radiographic pattern typical of TB where independent predictors of SNPT.     

A Novel Scoring System to Measure Radiographic Abnormalities and Related Spirometric Values in Cured Pulmonary Tuberculosis

Background

Despite chemotherapy, patients with cured pulmonary tuberculosis may result in lung functional impairment.

Objective

To evaluate a novel scoring system based on the degree of radiographic abnormalities and related spirometric values in patients with cured pulmonary tuberculosis.

Methods

One hundred and twenty seven patients with cured pulmonary tuberculosis were prospectively enrolled in a referral hospital specializing in respiratory diseases. Spirometry was performed and the extent of radiographic abnormalities was evaluated twice by each of two readers to generate a novel quantitative score. Scoring reproducibility was analyzed by the intra-class correlation coefficient (ICC) and the Bland-Altman method. Multiple linear regression models were performed to assess the association of the extent of radiographic abnormalities with spirometric values.

Results

The intra-observer agreement for scoring of radiographic abnormalities (SRA) showed an ICC of 0.81 (CI:95%, 0.67–0.95) and 0.78 (CI:95%, 0.65–0.92), for reader 1 and 2, respectively. Inter-observer reproducibility for the first measurement was 0.83 (CI:95%, 0.71–0.95), and for the second measurement was 0.74 (CI:95%, 0.58–0.90). The Bland-Altman analysis of the intra-observer agreement showed a mean bias of 0.87% and -0.55% and an inter-observer agreement of -0.35% and -1.78%, indicating a minor average systematic variability.After adjustment for age, gender, height, smoking status, pack-years of smoking, and degree of dyspnea, the scoring degree of radiographic abnormalities was significantly and negatively associated with absolute and percent predicted values of FVC: -0.07 (CI:95%, -0.01 to -0.04); -2.48 (CI:95%, -3.45 to -1.50); and FEV₁ -0.07 (CI:95%, -0.10 to -0.05); -2.92 (CI:95%, -3.87 to -1.97) respectively, in the patients studied.

Conclusion

The extent of radiographic abnormalities, as evaluated through our novel scoring system, was inversely associated with spirometric values, and exhibited good reliability and reproducibility. As intra-observer and inter-observer agreement of the SRA varied from good to excellent, the use of SRA in this setting appears acceptable.     

Prevalence of Pulmonary Tuberculosis among Adults in a Rural Sub-District of South India

Background

We conducted a survey to estimate point prevalence of bacteriologically positive pulmonary TB (PTB) in a rural area in South India, implementing TB program DOTS strategy since 2002.

Methods

Survey was conducted among persons ≥15 years of age in fifteen clusters selected by simple random sampling; each consisting of 5–12 villages. Persons having symptoms suggestive of PTB or history of anti-TB treatment (ATT) were eligible for sputum examination by smear microscopy for Acid Fast Bacilli and culture for Mycobacterium tuberculosis; two sputum samples were collected from each eligible person.Persons with one or both sputum specimen positive on microscopy and/or culture were labeled suffering from PTB. Prevalence was estimated after imputing missing values to correct for bias introduced by incompleteness of data.In six clusters, registered persons were also screened by X-ray chest. Persons with any abnormal shadow on X-ray were eligible for sputum examination in addition to those with symptoms and ATT. Multiplication factor calculated as ratio of prevalence while using both screening tools to prevalence using symptoms screening alone was applied to entire study population to estimate prevalence corrected for non-screening by X-ray.

Results

Of 71,874 residents ≥15 years of age, 63,362 (88.2%) were screened for symptoms and ATT. Of them, 5120 (8.1%) - 4681 (7.4%) with symptoms and an additional 439 (0.7%) with ATT were eligible for sputum examination. Spot specimen were collected from 4850 (94.7%) and early morning sputum specimens from 4719 (92.2%). Using symptom screening alone, prevalence of smear, culture and bacteriologically positive PTB in persons ≥15 years of age was 83 (CI: 57–109), 152 (CI: 108–197) and 196 (CI :145–246) per 100,000 population respectively. Prevalence corrected for non-screening by X-ray was 108 (CI: 82–134), 198 (CI: 153–243) and 254 (CI: 204–301) respectively.

Conclusion

Observed prevalence suggests further strengthening of TB control program.