Accuracy of C-reactive protein and a differentiated white cell count in diagnosing tuberculosis.

Background: Tuberculosis (TB) is treatable with a high cure rate. In South Africa, 70% of pulmonary TB is microbiologically confirmed. Autopsy studies of HIV-positive people found 45.7% undiagnosed TB cases. Objectives: The primary objective investigated whether CRP and a differentiated white cell count (WCC) and ratios thereof are useful screening tools for TB. Method: This retrospective cross-sectional study included adult patients admitted to two tertiary hospitals in Bloemfontein with TB workups between April 2016 and September 2019. National Health Laboratory Service (NHLS) provided laboratory data. Tuberculosis Xpert® MTB/RIF, Xpert® MTB/RIF Ultra and TB culture were used as reference standard for TB diagnosis. Results: The study population comprised 1294 patients; 15.1% had TB, 56.0% were male and 63.1% HIV-positive. Patients with TB were younger (p < 0.0001; 95% CI: -8;-3 years). In the total population, WCC had the highest area under the curve (0.59). White cell count (p < 0.0001), neutrophils (p = 0.0003) and lymphocytes (p = 0.0394) were lower in TB patients, and CRP-WCC ratio (CWR) (p = 0.0009) and CRP-lymphocyte ratio (CLR) (p = 0.0386) higher. In HIV-positive patients, WCC (p = 0.0003), neutrophils (p = 0.002) and lymphocytes (p = 0.0491) were lower in TB patients and CWR (p = 0.0043) higher. No parameter reached the World Health Organization screening targets of 70% specificity with 90% sensitivity. Conclusion: Differentiated WCC and CRP are not useful in screening hospitalised patients for TB in our setting. Contribution: Our study guides future research to augment current screening and diagnostic algorithms for TB, specifically in advanced HIV disease.

"Allergic bronchopulmonary aspergillosis misdiagnosed as smear negative pulmonary tuberculosis; a retrospective study from Pakistan".

BACKGROUND: Undiagnosed allergic bronchopulmonary aspergillosis (ABPA) can lead to chronic persistent symptoms. In country like Pakistan where tuberculosis (TB) is endemic, a significant proportion of ABPA patients are misdiagnosed as smear negative TB before reaching a diagnosis of ABPA due to chronicity of symptoms.This lead to empiric use of ATT(Anti-tuberculous therapy) and delay in primary diagnosis. The aim of the study is to determine such proportion of ABPA patients. MATERIAL AND METHODS: This retrospective study was conducted at the outpatient pulmonology clinic of a tertiary care hospital in Karachi, Pakistan from January 2017 to December 2018. Xpert MTB/Rif, TB smear and culture were performed in all patients to rule out active TB. RESULTS: A total 167 of ABPA patients were included. Mean age of the patients was 41.9 ± 13.0 years, 91(54.5%) were female and 71 (42.5%) patients had received ATT in past. Out of these 71 patients, 63 (88.7%) patients were diagnosed as smear negative TB and received empiric ATT. Among 63 patients, 52 (82.5%) patient had received ATT once, 8 (12.6%) twice and 3 (4.7%) patients had received empiric ATT thrice. Of these 27 (16.16%) patients had already developed long term complications at the time of diagnosis of ABPA and 17 (62.96%) patients were in empiric TB treatment group. CONCLUSION: Patient with ABPA frequently received empiric ATT as smear negative TB in high TB burden country. This results in over diagnosis of TB and unnecessary use of global resource. When Gene Xpert negative alternate diagnosis should be considered.

Prevalence of pulmonary mycoses in smear-negative patients with suspected tuberculosis in the Brazilian Amazon.

BACKGROUND: Pulmonary mycoses resemble clinically and radiologically chronic pulmonary tuberculosis. Studies describing the prevalence, etiology and clinical features of pulmonary mycosis are of crucial importance in the Brazilian Amazon. AIMS: To estimate the frequency of pulmonary mycoses in smear-negative tuberculosis patients; to describe their demographic, epidemiological, and clinical characteristics; and to evaluate diagnostic methods. METHODS: A cross-sectional study was conducted at two tuberculosis reference institutions in Amazonas, Brazil. We included 213 patients and collected clinical data, blood and induced sputum to perform serological, direct microscopy, microbiologic culture and PCR-based assays to identify infections caused by Aspergillus fumigatus, Paracoccidioides brasiliensis, Histoplasma capsulatum, Cryptococcus, and HIV. Chest computed tomography was also performed. RESULTS: Pulmonary mycoses were diagnosed in 7% (15/213) of the cases, comprising ten aspergillosis cases, three cases of paracoccidioidomycosis and one case each of histoplasmosis and cryptococcosis. Among the patients with pulmonary mycoses, 86.7% were former tuberculosis patients. The most significant clinical characteristics associated with pulmonary mycoses were cavity-shaped lung injuries, prolonged chronic cough and hemoptysis. CONCLUSIONS: Our study confirmed the high prevalence of pulmonary mycoses in smear-negative tuberculosis patients in the Brazilian Amazon.

Smear microscopy as a diagnostic tool of tuberculosis: Review of smear negative cases, frequency, risk factors, and prevention criteria.

Tuberculosis is one of the global health problems, the estimated deaths due to TB was around 2 million in the year 2013. Failure in early diagnosis and providing suitable treatment leads to increase the prognosis of the disease. Smear microscopy is used in many countries as a primary diagnosis of TB especially in the district poor facility laboratories, where smear negative frequency is high. This review aimed to reflects the importance of smear negative tuberculosis as a source of infection and poor prognosis of TB treatment and prevention. In addition to, discuss the possible causes and suggests solutions to improve the yields of smear microscopy.

Polymerase chain reaction test in induced sputum of patients with pulmonary tuberculosis.

INTRODUCTION: Induced sputum (IS) is an alternative method of obtaining sputum, but IS smears are frequently negative. Culture is more time consuming in its results, and less useful to guide the diagnosis. Polymerase chain reaction (PCR) is the most common methodology for rapid diagnosis of tuberculosis (TB), and few studies evaluated its role in IS samples. OBJECTIVES: The objective of this study is to determine the diagnostic yield of PCR for TB compared with culture in IS samples. MATERIALS AND METHODS: Prospective study. Inpatients and outpatients of >18 years with respiratory symptoms suggestive of PTB were invited to participate. The subjects were interviewed using a standardized questionnaire, and collected IS. Three samples were obtained for AFB smear and culture. A fourth sample was obtained for PCR test. RESULTS: A total of 116 IS samples were evaluated. The sensitivity, specificity, positive predictive value and negative predictive values of PCR were 95.2%, 48.4%, 29.0% and 97.9%, respectively. The area under the receiver operating characteristic curve was .72 for the PCR test (P < .0001). CONCLUSIONS: Although the PCR specificity could be underestimated, if we consider PCR to be more sensitive than the culture method used, we believed that these PCR-positive tests mean false positives. The results of PCR should always be interpreted carefully in conjunction with clinical information.

Increased detection of smear-negative pulmonary tuberculosis by GeneXpert MTB/RIF® assay after bleach concentration.

OBJECTIVE/BACKGROUND: The GeneXpert MTB/RIF assay (Xpert) was endorsed as the initial diagnostic tool in people suspected of human immunodeficiency virus-associated or drug-resistant tuberculosis (TB). However, information regarding the performance of Xpert for diagnosing smear-negative TB in high burden settings remains limited. We evaluated the diagnostic accuracy of Xpert and the impact of bleach concentration on the performance of Xpert using smear-negative sputum samples from human immunodeficiency virus-negative patients. METHODS: One spot and one morning smear-negative sputum samples per patient were examined using Xpert and culture at the Mycobacteriology Research Center of Jimma University, Ethiopia. The sputum culture on both Löwenstein-Jensen and/or Mycobacteria Growth Indicator Tube was the gold-standard. RESULTS: Of 185 smear-negative presumptive pulmonary TB cases, 19 (10.3%) had culture-proven TB. The sensitivity of Xpert on spot and morning sputum was similar (63.2%). Testing two specimens per patient insignificantly increased the sensitivity of Xpert. Bleach concentration and pelleting improved the sensitivity of Xpert over unprocessed sputum in paired samples (73.8% vs. 63.2%) without affecting the specificity (95%). Bleach concentration and pelleting allowed an additional seven cases of TB (missed on the first and second direct Xperts) to be detected, five of which were from culture-negative cases. CONCLUSION: Testing of a single sputum sample by Xpert can reach reasonable sensitivity and results would be available on the same day, avoiding loss of patients and treatment delay. The sensitivity of Xpert was improved after bleach concentration and pelleting, although its added value needs further study on a larger scale.

Pulmonary aspergilloma: An evasive disease.

Aspergillomas are often misdiagnosed as tuberculosis (TB) in developing countries where the prevalence of TB is high, hemoptysis is often equated with TB, and most patients are diagnosed clinically. This report describes the case of a patient being treated for smear-negative TB who presented with hemoptysis and was found to have an aspergilloma.

Accuracy of bronchoalveolar lavage enzyme-linked immunospot assay to diagnose smear-negative tuberculosis: a meta-analysis.

PURPOSE: While the bronchoalveolar lavage enzyme-linked immunospot assay (BAL-ELISPOT) shows promise for diagnosing smear-negative tuberculosis, its accuracy remains controversial. We meta-analyzed the available evidence to obtain a clearer understanding of the diagnostic accuracy. METHODS: Studies of the diagnostic performance of ELI-SPOT on smear-negative tuberculosis were identified through systematic searches of the PubMed and EMBASE databases. Pooled data on sensitivity, specificity and other measures of accuracy were meta-analyzed using a random-effects model. Summary receiver operating characteristic curves were used to assess overall test performance. RESULTS: A total of 7 studies were included in the meta-analysis. Diagnostic performance was as follows: sensitivity, 0.89 (95% CI 0.84 to 0.93); specificity, 0.78 (95% CI 0.74 to 0.81); positive likelihood ratio, 4.2 (95% CI 2.42 to 7.28); negative likelihood ratio, 0.14 (95% CI 0.06 to 0.33); diagnostic odds ratio, 36.16 (95% CI 9.70 to 134.73); and area under the curve, 0.9605 (SEM 0.0247). CONCLUSIONS: Available evidence suggests that BAL-ELISPOT may perform better than blood-ELISPOT for both screening and confirming a diagnosis of smear-negative tuberculosis. Nevertheless, BAL-ELISPOT should be not used alone but rather in parallel with clinical manifestations and conventional tests to ensure reliable diagnosis.

Manual liquid culture on simple Middlebrook 7H9 or MGIT for the diagnosis of smear-negative pulmonary tuberculosis.

OBJECTIVES: To compare the performance of liquid culture on simple Middlebrook 7H9 to the one of manual mycobacterial growth indicator tube (MGIT) and solid culture on Ogawa for the diagnosis of smear-negative tuberculosis (SN-TB) in a high-burden, resource-constrained setting. METHODS: Sputum samples from patients with clinical suspicion of SN-PTB admitted to two-third-level hospitals in Lima between September 2005 and May 2008 were cultured in parallel on simple Middlebrook 7H9, manual MGIT and Ogawa. A case of SN-TB was defined as one with a positive culture in any medium. RESULTS: Among samples from 542 patients, 151 (28%) cases of SN-TB were identified. The sensitivity of Middlebrook 7H9 (0.76, 95% CI 0.69-0.83) was not substantially different from that of MGIT (0.85, 95% CI 0.79-0.91). Ogawa had the lowest sensitivity (0.63, 95% CI 0.55-0.71). The median turnaround time was similar for both liquid media (18 days), and it was shorter than that of Ogawa (30 days). CONCLUSIONS: Culture on simple Middlebrook 7H9 performs almost as well as MGIT, at a probably more affordable cost. Further studies on the cost-effectiveness of this overlooked technique should be performed.