Joy Sarojini Michael

Rapid Diagnosis of Tuberculosis with the Xpert MTB/RIF Assay in High Burden Countries: A Cost-Effectiveness Analysis

A cost-effectiveness study by Frank Cobelens and colleagues reveals that Xpert MTB/RIF is a cost-effective method of tuberculosis diagnosis that is suitable for use in low- and middle-income settings.

Mycological profile of fungal sinusitis: An audit of specimens over a 7-year period in a tertiary care hospital in Tamil Nadu.

BACKGROUND Fungi are being increasingly implicated in the etiopathology of rhinosinusitis. Fungal sinusitis is frequently seen in diabetic or immunocompromised patients, although it has also been reported in immunocompetent individuals. Invasive fungal sinusitis, unless diagnosed early and treated aggressively, has a high mortality rate. AIM Our aim was to look at the mycological and clinical aspects of fungal sinusitis in a tertiary referral center in Tamil Nadu. DESIGN This is a retrospective audit conducted on fungal culture positive sinus samples submitted to the Microbiology department from January 2000 to August 2007. Relevant clinical and histopathological details were analysed. RESULTS A total of 211 culture-positive fungal sinusitis samples were analysed. Of these, 63% had allergic fungal sinusitis and 34% had invasive fungal sinusitis. Aspergillus flavus was the most common causative agent of allergic fungal sinusitis and Rhizopus arrhizus was the most common causative agent of acute invasive sinusitis. A significant proportion of these patients did not have any known predisposing factors. CONCLUSION In our study, the etiology of fungal sinusitis was different than that of western countries. Allergic fungal sinusitis was the most common type of fungal sinusitis in our community. Aspergillus sp was the most common causative agent in both allergic and chronic invasive forms of the disease.

Tuberculosis infection among young nursing trainees in South India.

Background Among healthcare workers in developing countries, nurses spend a large amount of time in direct contact with tuberculosis (TB) patients, and are at high risk for acquisition of TB infection and disease. To better understand the epidemiology of nosocomial TB among nurses, we recruited a cohort of young nursing trainees at Christian Medical College, a large, tertiary medical school hospital in Southern India. Methodology/Principal Findings Among 535 nursing students enrolled in 2007, 468 gave consent to participate, and 436 underwent two-step tuberculin skin testing (TST). A majority (95%) were females, and almost 80% were under 22 years of age. Detailed TB exposure information was obtained using interviews and clinical log books. Prevalence of latent TB infection (LTBI) was estimated using Bayesian latent class analyses (LCA). Logistic regression analyses were done to determine the association between LTBI prevalence and TB exposure and risk factors. 219 of 436 students (50.2%, 95% CI: 45.4–55.0) were TST positive using the 10 mm or greater cut-off. Based on the LCA, the prevalence of LTBI was 47.8% (95% credible interval 17.8% to 65.6%). In the multivariate analysis, TST positivity was strongly associated with time spent in health care, after adjusting for age at entry into healthcare. Conclusions Our study showed a high prevalence of LTBI even in young nursing trainees. With the recent TB infection control (TBIC) policy guidance from the World Health Organization as the reference, Indian healthcare providers and the Indian Revised National TB Control Programme will need to implement TBIC interventions, and enhance capacity for TBIC at the country level. Young trainees and nurses, in particular, will need to be targeted for TBIC interventions.

Risk factors for MDR and XDR-TB in a tertiary referral hospital in India.

Background India has a high burden of drug resistant TB, although there are few data on XDR-TB. Although XDR-TB has existed previously in India, the definition has not been widely applied, and surveillance using second line drug susceptibility testing has not been performed. Our objective was to analyze clinical and demographic risk factors associated with isolation of MDR and XDR TB as compared to susceptible controls, at a tertiary center. Methodology/Findings Retrospective chart review based on positive cultures isolated in a high volume mycobacteriology laboratory between 2002 and 2007. 47 XDR, 30 MDR and 117 susceptible controls were examined. Drug resistant cases were less likely to be extrapulmonary, and had received more previous treatment regimens. Significant risk factors for XDR-TB included residence outside the local state (OR 7.43, 3.07-18.0) and care costs subsidized (OR 0.23, 0.097-0.54) in bivariate analysis and previous use of a fluoroquinolone and injectable agent (other than streptomycin) (OR 7.00, 95% C.I. 1.14-43.03) and an initial treatment regimen which did not follow national guidelines (OR 5.68, 1.24-25.96) in multivariate analysis. Cavitation and HIV did not influence drug resistance. Conclusions/Significance There is significant selection bias in the sample available. Selection pressure from previous treatment and an inadequate initial regimen increases risk of drug resistance. Local patients and those requiring financial subsidies may be at lower risk of XDR-TB.

Performance of Xpert MTB/RIF on pleural tissue for the diagnosis of pleural tuberculosis

To the Editor: Tuberculosis (TB) remains the second leading cause of death from an infectious disease in adults. Extrapulmonary TB (EPTB) accounts for about 25% of all cases of active TB. Pleural TB is the second most common manifestation of EPTB. Existing tests for the diagnosis of pleural TB have major limitations in terms of accuracy, time to diagnosis and drug resistance testing, and require special expertise for sample acquisition and interpretation of the results. Biopsy of the pleural tissue for combined histological examination and culture is considered the diagnostic gold standard, albeit imperfect [1, 2]. The Xpert MTB/RIF assay (Xpert; Cepheid, Sunnyvale, CA, USA) is a rapid, World Health Organization (WHO) endorsed, automated PCR test optimised for respiratory specimens that can detect both Mycobacterium tuberculosis (MTB) and rifampicin resistance [3, 4]. Given the limitations of available tests for the diagnosis of pleural TB, several studies have evaluated the performance of Xpert using pleural fluid as a sample type. Overall, these studies show limited accuracy with sensitivity averaging around 44% [5–7]. However, the preferred specimen for the diagnosis of pleural TB is pleural tissue. To date, the evaluation of Xpert performed on pleural tissue has been limited to isolated samples within larger studies [4, 6, 7]. We enrolled consecutive adult patients that were evaluated for pleural TB in the pulmonary clinic and inpatient ward at the Christian Medical College, Vellore, India. Pleural TB was suspected based on clinical symptoms and radiographic evidence of a pleural effusion. Information on demographics, comorbidities, presenting symptoms and results of diagnostic evaluation were collected prospectively. The institutional review boards of the Christian Medical College …

Does solid culture for tuberculosis influence clinical decision making in India

SETTING Medical units at an academic tertiary referral hospital in Southern India. OBJECTIVE To investigate the impact of solid culture on Löwenstein-Jensen medium on clinical decision making. DESIGN In a retrospective review of 150 culture-positive and 150 culture-negative consecutively sampled tuberculosis (TB) suspects, treatment decisions were analysed at presentation, after the availability of culture detection results and after the availability of drug susceptibility testing (DST) culture results. RESULTS A total of 124 (82.7%) culture-positive patients and 35 (23.3%) culture-negative patients started anti-tuberculosis treatment prior to receiving their culture results; 101 patients (33.7%) returned for their results; two (1.3%) initiated treatment based on positive culture and no culture-negative patients discontinued treatment. DST was performed on 119 (79.3%) positive cultures: 30 (25.2%) showed any resistance, eight (6.7%) showed multidrug resistance and one (0.84%) showed extensively drug-resistant TB. Twenty-eight patients (23.5%) returned for their DST results. Based on DST, treatment was modified in four patients (3.4%). CONCLUSION Using solid culture, 150 cultures need to be tested for one treatment modification and 30 for DST. The cost of the widespread application of culture will need to be balanced against its impact on treatment decisions in India.

Unusual presentation of entomophthoromycosis

Rhinoentomophthoromycosis caused by Conidiobolus sp commonly presents as a chronic granulomatous lesion that affects the rhinofacial subcutaneous tissue. We present an 18-year-old girl who presented with progressive bilateral proptosis and loss of vision since 2 weeks. Biopsy and fungal cultures confirmed diagnosis of Conidiobolus sp infection of the paranasal sinuses bilaterally with orbital extension and blindness. The clinical picture was complicated by the presence of sputum-positive cavitatory pulmonary tuberculosis, which was diagnosed at the same time. To our knowledge, this is the first such case to be reported from India. We also discuss the management of entomophthoromycosis. Despite many reports of success, there remains no consensus on the treatment of Conidiobolus infections of the nose and the paranasal sinuses with antifungal agents.

Evaluation of the microscopic observational drug susceptibility assay for rapid and efficient diagnosis of multi-drug resistant tuberculosis.

PURPOSE Tuberculosis (TB) is endemic in India and the burden of multi-drug-resistant tuberculosis (MDR-TB) is high. Early detection of MDR-TB is of primary importance in controlling the spread of TB. The microscopic observational drug susceptibility (MODS) assay has been described as a cost-effective and rapid method by which mycobacterial culture and the drug susceptibility test (DST) can be done at the same time. MATERIALS AND METHODS A total of 302 consecutive sputum samples that were received in an accredited mycobacteriology laboratory for conventional culture and DST were evaluated by the MODS assay. RESULTS In comparison with conventional culture on Lowenstein Jensen (LJ) media, the MODS assay showed a sensitivity of 94.12% and a specificity of 89.39% and its concordance with the DST by the proportion method on LJ media to isoniazid and rifampicin was 90.8% and 91.5%, respectively. The turnaround time for results by MODS was 9 days compared to 21 days by culture on LJ media and an additional 42 days for DST by the 1% proportion method. The cost of performing a single MODS assay was Rs. 250/-, compared to Rs. 950/- for culture and 1st line DST on LJ. CONCLUSION MODS was found to be a sensitive and rapid alternative method for performing culture and DST to identify MDR-TB in resource poor settings.

Tuberculosis in otorhinolaryngology: clinical presentation and diagnostic challenges.

Tuberculosis affects all tissues of the body, although some more commonly than the others. Pulmonary tuberculosis is the most common type of tuberculosis accounting for approximately 80% of the tuberculosis cases. Tuberculosis of the otorhinolaryngeal region is one of the rarer forms of extrapulmonary tuberculosis but still poses a significant clinical and diagnostic challenge. Over three years, only five out of 121 patients suspected to have tuberculosis of the otorhinolaryngeal region (cervical adenitis excluded) had Mycobacterium tuberculosis culture-proven disease. Additional 7 had histology-proven tuberculosis. Only one patient had concomitant sputum-positive pulmonary tuberculosis. We look at the various clinical and laboratory aspects of tuberculosis of the otorhinolaryngeal region that would help to diagnose this uncommon but important form of extrapulmonary tuberculosis.

Impact of point-of-care implementation of Xpert® MTB/RIF: product vs. process innovation.

BACKGROUND Both product innovation (e.g., more sensitive tests) and process innovation (e.g., a point-of-care [POC] testing programme) could improve patient outcomes. OBJECTIVE To study the respective contributions of product and process innovation in improving patient outcomes. DESIGN We implemented a POC programme using Xpert(®) MTB/RIF in an out-patient clinic of a tertiary care hospital in India. We measured the impact of process innovation by comparing time to diagnosis with routine testing vs. POC testing. We measured the impact of product innovation by comparing accuracy and time to diagnosis using smear microscopy vs. POC Xpert. RESULTS We enrolled 1012 patients over a 15-month period. Xpert had high accuracy, but the incremental value of one Xpert over two smears was only 6% (95%CI 3-12). Implementing Xpert as a routine laboratory test did not reduce the time to diagnosis compared to smear-based diagnosis. In contrast, the POC programme reduced the time to diagnosis by 5.5 days (95%CI 4.3-6.7), but required dedicated staff and substantial adaptation of clinic workflow. CONCLUSION Process innovation by way of a POC Xpert programme had a greater impact on time to diagnosis than the product per se, and can yield important improvements in patient care that are complementary to those achieved by introducing innovative technologies.