Manish Soneja

HIV & immune reconstitution inflammatory syndrome (IRIS)

Antiretroviral therapy (ART) initiation in HIV-infected patients leads to recovery of CD4+T cell numbers and restoration of protective immune responses against a wide variety of pathogens, resulting in reduction in the frequency of opportunistic infections and prolonged survival. However, in a subset of patients, dysregulated immune response after initiation of ART leads to the phenomenon of immune reconstitution inflammatory syndrome (IRIS). The hallmark of the syndrome is paradoxical worsening of an existing infection or disease process or appearance of a new infection/disease process soon after initiation of therapy. The overall incidence of IRIS is unknown, but is dependent on the population studied and the burden of underlying opportunistic infections. The immunopathogenesis of the syndrome is unclear and appears to be result of unbalanced reconstitution of effector and regulatory T-cells, leading to exuberant inflammatory response in patients receiving ART. Biomarkers, including interferon-γ (INF-γ), tumour necrosis factor-α (TNF-α), C-reactive protein (CRP) and inter leukin (IL)-2, 6 and 7, are subject of intense investigation at present. The commonest forms of IRIS are associated with mycobacterial infections, fungi and herpes viruses. Majority of patients with IRIS have a self-limiting disease course. ART is usually continued and treatment for the associated condition optimized. The overall mortality associated with IRIS is low; however, patients with central nervous system involvement with raised intracranial pressures in cryptococcal and tubercular meningitis, and respiratory failure due to acute respiratory distress syndrome (ARDS) have poor prognosis and require aggressive management including corticosteroids. Paradigm shifts in management of HIV with earlier initiation of ART is expected to decrease the burden of IRIS in developed countries; however, with enhanced rollout of ART in recent years and the enormous burden of opportunistic infections in developing countries like India, IRIS is likely to remain an area of major concern.

Comparative Evaluation of GenoType MTBDRplus Line Probe Assay with Solid Culture Method in Early Diagnosis of Multidrug Resistant Tuberculosis (MDR-TB) at a Tertiary Care Centre in India

Background The objectives of the study were to compare the performance of line probe assay (GenoType MTBDRplus) with solid culture method for an early diagnosis of multidrug resistant tuberculosis (MDR-TB), and to study the mutation patterns associated with rpoB, katG and inhA genes at a tertiary care centre in north India. Methods In this cross-sectional study, 269 previously treated sputum-smear acid-fast bacilli (AFB) positive MDR-TB suspects were enrolled from January to September 2012 at the All India Institute of Medical Sciences hospital, New Delhi. Line probe assay (LPA) was performed directly on the sputum specimens and the results were compared with that of conventional drug susceptibility testing (DST) on solid media [Lowenstein Jensen (LJ) method]. Results DST results by LPA and LJ methods were compared in 242 MDR-TB suspects. The LPA detected rifampicin (RIF) resistance in 70 of 71 cases, isoniazid (INH) resistance in 86 of 93 cases, and MDR-TB in 66 of 68 cases as compared to the conventional method. Overall (rifampicin, isoniazid and MDR-TB) concordance of the LPA with the conventional DST was 96%. Sensitivity and specificity were 98% and 99% respectively for detection of RIF resistance; 92% and 99% respectively for detection of INH resistance; 97% and 100% respectively for detection of MDR-TB. Frequencies of katG gene, inhA gene and combined katG and inhA gene mutations conferring all INH resistance were 72/87 (83%), 10/87 (11%) and 5/87 (6%) respectively. The turnaround time of the LPA test was 48 hours. Conclusion The LPA test provides an early diagnosis of monoresistance to isoniazid and rifampicin and is highly sensitive and specific for an early diagnosis of MDR-TB. Based on these findings, it is concluded that the LPA test can be useful in early diagnosis of drug resistant TB in high TB burden countries.

Evaluation of Xpert MTB/RIF assay performance in diagnosing extrapulmonary tuberculosis among adults in a tertiary care centre in India

To the Editor: According to the World Health Organization Global Tuberculosis Report from 2013, there were 8.6 million incident tuberculosis (TB) cases globally and India alone contributed 26% to this global scenario [1]. Of the five countries with the largest number of TB incident cases in 2012, India tops the list [1]. Epidemiological data suggest that extrapulmonary TB (EPTB) constitutes about 15–20% of all TB cases, but among HIV-TB co-infection it accounts for 50% of the cases [2]. Out of 1 183 373 new TB cases notified globally, 234 029 (20%) were reported to be cases of EPTB [1]. Difficulty in sampling from the extrapulmonary sites and the paucibacillary nature of the specimens make EPTB a diagnostic challenge. Dependency on smear microscopy in these samples may lead to higher false negative rates due to the low sensitivity of this technique. Mycobacterium tuberculosis (MTB) culture is quite a protracted technique, requiring well-trained laboratory personnel, and delay in diagnosis can cause more harm as the treatment is often started empirically. Rapid nucleic acid amplification tests are emerging extensively to provide better yield for rapid diagnosis of TB. The Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is an automated, hemi-nested real-time PCR for detecting MTB complex and rifampin (RIF) resistance, which was initially evaluated for pulmonary specimens in large studies [3–5]. The present communication reports the performance of Xpert MTB/RIF in EPTB samples, with a large sample size from a single centre in a country with a high TB burden. All EPTB samples from indoor as well as outdoor facilities of the All India Institute of Medical Sciences (AIIMS) hospital, New Delhi, India, were received in the Tuberculosis Laboratory (accredited Intermediate Reference Laboratory …

Aetiology, outcomes & predictors of mortality in acute respiratory distress syndrome from a tertiary care centre in north India

Background & objectives: Acute respiratory distress syndrome (ARDS) is a common disorder in critically ill patients and is associated with high mortality. There is a paucity of literature on this condition from developing countries. This prospective observational study was designed to find out the aetiology, outcomes and predictors of mortality in ARDS. Methods: Sixty four consecutive patients who satisfied American-European Consensus Conference (AECC) definition of ARDS from medical Intensive Care Unit (ICU) of a tertiary care centre in New Delhi, India, were enrolled in the study. Demographic, biochemical and ventilatory variables were recorded for each patient. Baseline measurements of serum interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α), procalcitonin (PCT) and high sensitivity C-reactive protein (hsCRP) were performed. Results: Common causes of ARDS included pneumonia [44/64 (68.7%)], malaria [9/64 (14.1%)] and sepsis [8/64 (12.5%]. Eight of the 64 (12.5%) patients had ARDS due to viral pneumonia. The 28-day mortality was 36/64 (56.2%). Independent predictors of mortality included non-pulmonary organ failure, [Hazard ratio (HR) 7.65; 95% CI 0.98-59.7, P=0.05], Simplified Acute Physiology Score (SAPS-II) [HR 2.36; 95% CI 1.14-4.85, P=0.02] and peak pressure (Ppeak) [HR 1.13; 95% CI 1.00-1.30, P = 0.04] at admission. Interpretation & conclusions: Bacterial and viral pneumonia, malaria and tuberculosis resulted in ARDS in a considerable number of patients. Independent predictors of mortality included non-pulmonary organ failure, SAPS II score and Ppeak at baseline. Elevated levels of biomarkers such as TNF-α, PCT and hsCRP at admission might help in identifying patients at a higher risk of mortality.

Malignancies in human immunodeficiency virus infected patients in India: Initial experience in the HAART era.

Background & objectives: Limited data are available on malignancies in human immunodeficiency virus (HIV)-infected patients from India. We undertook this study to assess the frequency and spectrum of malignancies in HIV-infected adult patients during the first eight years of highly active antiretroviral therapy (HAART) rollout under the National ART Programme at a tertiary care centre in New Delhi, India. Methods: Retrospective analysis of records of patients registered at the ART clinic between May 2005 and December 2013 was done. Results: The study included 2598 HIV-infected adult patients with 8315 person-years of follow up. Malignancies were diagnosed in 26 patients with a rate of 3.1 (IQR 2.1-4.5) cases per 1000 person-years. The median age for those diagnosed with malignancy was 45 (IQR 36-54) yr, which was significantly (P<0.01) higher compared with those not developing malignancies 35 (IQR 30-40) yr. The median baseline CD4+ T-cell count in patients with malignancy was 135 (IQR 68-269) cells/µl compared to 164 (IQR 86-243) cells/µl in those without malignancies. AIDS-defining cancers (ADCs) were seen in 19 (73%) patients, while non-AIDS-defining cancers (NADCs) were observed in seven (27%) patients. Malignancies diagnosed included non-Hodgkins lymphoma (16), carcinoma cervix (3), Hodgkins lymphoma (2), carcinoma lung (2), hepatocellular carcinoma (1), and urinary bladder carcinoma (1). One patient had primary central nervous system lymphoma. There was no case of Kaposis sarcoma. Interpretation & conclusions: Malignancies in HIV-infected adult patients were infrequent in patients attending the clinic. Majority of the patients presented with advanced immunosuppression and the ADCs, NHL in particular, were the commonest malignancies.

Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity

Background & objectives: The N-acetyltransferase 2 (NAT2) gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH). Methods: In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs. Results: Frequency of slow-acetylator genotype was commonly encountered and was not significantly different between DIH (82.8%) and non-DIH (77.2%) patients. However, the genotypic distribution of variant NAT2*5/*7 amongst slow-acetylator genotypes was significantly higher in DIH (56%) group as compared to non-DIH (39%) group (odds ratio 2.02; P=0.006). Interpretation & conclusions: The present study demonstrated no association between NAT2 genotype and DIH in the north Indian patients with tuberculosis.

Evaluation of Xpert® Mycobacterium tuberculosis/rifampin in sputum-smear negative and sputum-scarce patients with pulmonary tuberculosis using bronchoalveolar lavage fluid

Context: Sputum smear-negative and sputum-scarce pulmonary tuberculosis (PTB) is a diagnostic challenge. Xpert® Mycobacterium tuberculosis/rifampin (MTB/RIF) provides a rapid diagnosis on high-quality biological specimen obtained by bronchoscopy. Aims: The aim of this study is to evaluate Xpert® MTB/RIF on bronchoalveolar lavage (BAL) fluid in sputum smear-negative and sputum-scarce PTB patients. Settings: Tertiary care hospital in India. Design: This was prospective observational study. Materials and Methods: Between January 2015 and November 2016, we prospectively recruited sputum-smear negative and sputum-scarce patients under evaluation for PTB and performed BAL. Sensitivity, specificity, positive, and negative predictive values were calculated for the diagnosis of PTB on BAL fluid for acid-fast bacilli smear and Xpert® MTB/RIF using liquid culture as the reference standard and compared to the final diagnosis based on composite reference standard. Sensitivity, specificity, and predictive values were calculated with 95% class intervals. McNemars test was used for comparison of sensitivities. Results: Of the 60 patients included, 52 (88.3%) had a final diagnosis of PTB and 16 (26.7%) were culture confirmed. Xpert® MTB/RIF had a sensitivity and specificity of 81% (54%–96%) and 73% (56%–85%) in culture confirmed cases; 46% (32%–60%) and 100% (63%–100%) for the final diagnosis; 32% (17%–51%) and 100% (54%–100%) in culture negative cases, respectively. Culture had a sensitivity of 32% (20%–47%) for the final diagnosis. Conclusions: In sputum smear-negative and sputum-scarce patients with clinico-radiological features of PTB Xpert® MTB/RIF has good sensitivity for diagnosis on BAL fluid. It is useful even when cultures are negative.

Sleep quality and quantity in intensive care unit patients: A cross-sectional study

Introduction: Lack of restorative sleep and altered sleep-wake cycle is a frequent problem among patients admitted to the Intensive Care Unit (ICU). This study was conducted to estimate the prevalence of poor sleep and patients perspective of factors governing poor sleep in the ICU. Materials and Methods: A cross-sectional study was performed in medical ICU of a tertiary care hospital. A total of 32 patients admitted to the ICU for at least 24 h were recruited. A 72-h actigraphy was done followed by a subjective assessment of sleep quality by the Richards-Campbell Sleep Questionnaire (RCSQ). Patients perspective of sleep quality and quantity and possible risk factors for poor sleep were recorded. Results: Poor sleep (defined as RCSQ <50, sensitivity 88% and specificity 87%) was found in 15 out of the 32 patients (47%). The prevalence of poor sleep was higher among patients on mechanical ventilation (n = 15) (66.7% vs. 33.3%, P < 0.05). Patients with poor sleep had higher age (median age [in years] 42.8 vs. 31.4, P = 0.008), acute physiology, and chronic health evaluation II score (mean 14 ± 5.15 vs. 9.3 ± 5.64, P = 0.02), SAPS 3 score (62.7 ± 8.9 vs. 45.6 ± 10.5, P ≤ 0.0001), and worse actigraphy parameters. Only 55.63% of total sleep time was in the night (2200–0600). All patients had discomfort from indwelling catheters and suctioning of endotracheal tubes. All patients suggested that there be a minimum interruption in the sleep for interventions or medications. Conclusion: There is a high prevalence of poor sleep among patients admitted to the ICU. There is a dire need to minimize untimely interventions and design nonpharmacological techniques to allow patients to sleep comfortably.

Nosocomial pneumonia: Search for an empiric and effective antibiotic regimen in high burden tertiary care centre

The clinical practice guidelines on nosocomial pneumonia recommends an empirical regimen that would work in 95% of the patients based on the local antibiogram. The aim of the study was development of an antibiogram for guiding empiric therapy in settings with high prevalence of multi-drug resistant organisms. A retrospective review of electronic health records (e-hospital portal) was done to analyze all respiratory isolates from patients admitted in medical wards and intensive care unit between May 2016 and May 2017. The samples included brocho-alveolar lavage (BAL), mini broncho-alveolar lavage (mini-BAL) and endotracheal aspirate. The sensitivity pattern (combined and individual) of all bacterial isolates were analysed for commonly used antibiotics and their combinations. Out of the 269 isolates, the most common organisms were Pseudomonas aeruginosa (125, 46%), Acinetobacter baumanni (74, 27%) and Klebsiella pneumoniae (50, 19%). Cefoperazone-sulbactam (43%) had the best sensitivity pattern overall. Cefoperazone-sulbactam plus amikacin (56%) was the combination with the best combined sensitivity overall. There is a high prevalence of resistance in the commonly implicated organisms to the available antibiotics. There is an urgent need for implementation of effective anti-microbial stewardship programmes and development of newer antimicrobials.

Atypical presentation of pyogenic iliopsoas abscess in two cases

Iliopsoas abscess (IPA) is an uncommon diagnosis in medical wards. Herein, we present two unusual cases of IPA. First patient was an elderly diabetic patient who had gas-forming bilateral IPA caused by Escherichia coli. This infection proved fatal and patient succumbed on third day of hospital admission. Second patient was a young boy who had right sided sacroilitis with IPA. Staphylococcus aureus was isolated from the pus culture and patient was successfully treated without any sequelae.