Comparative study on complications and difficulties in laparoscopy in female genital tuberculosis cases versus non-tuberculosis cases.

BACKGROUND AND OBJECTIVE: Female genital tuberculosis (FGTB) is an important type of extrapulmonary tuberculosis (TB) associated with morbidity especially infertility in developing countries. Laparoscopy may be difficult and hazardous in FGTB. The aim of the study was to observe the difficulties and complications of laparoscopy in FGTB cases. MATERIALS AND METHODS: It was a prospective study over 12 years' period on 412 cases of diagnostic laparoscopy performed on FGTB cases with infertility. All patients underwent history taking and clinical examination and endometrial sampling for acid-fast bacilli (AFB) microscopy, culture, polymerase chain reaction (PCR), gene Xpert (last 212 cases) and histopathological evidence of epithelioid granuloma. Another 412 cases of diagnostic laparoscopy in the absence of FGTB performed during same time were taken as controls from the pool of non-TB cases. Various difficulties and complications were noted in both groups and statistical analysis was done. RESULTS: Mean age, parity, body mass index and duration of infertility were 26.8 versus 25.4 years, 0.32 versus 0.28, 23.15 versus 25.28 Kg/m 2 and 4.15 versus 5.12 years, respectively. Primary and secondary infertility was seen in 78.6% and 20.38% of cases in the study group and 74.75% and 25.24% in the control group, respectively. Endometrial biopsy showed AFB microscopy in 5.3%, culture in 6.3%, epithelioid granuloma in 15.77% and on peritoneal biopsy granuloma in 6.55%, positive PCR in 368 (89.32%) and positive gene Xpert in 38 out of 212 (17.92%, out of last 212 cases). Definite findings of FGTB were seen in 171 (41.50%) cases. Probable findings of FGTB were seen in 241 (58.49%) cases. Various complications were difficulty in the creation of pneumoperitoneum or insertion of trocar and cannula in 16.74% and 13.10% of cases as compared to 1.94% and 1.69% in the control group. Excessive bleeding was seen in 5.09% versus 0.97% cases, respectively. Various injuries observed were bowel injury in 1.69% versus 0.24% cases (small bowel in 1.21% vs. 0.24%, large bowel in 0.48% vs. 0.1%), while bladder injury was seen in 0.97% versus 0.24% cases, subacute intestinal obstruction was seen in 5.8% versus 0.72% cases respectively while flare up of TB was seen in 5.09% versus 0% in cases and controls, respectively. Wound infection was seen in 8.48% versus 1.25% cases, respectively. INTERPRETATION AND CONCLUSION: FGTB is associated with increased complications and difficulties as compared to laparoscopy in other cases.

Breakthrough infection among healthcare personnel following exposure to COVID-19: Experience after one year of the world's largest vaccination drive.

Context: The COVID-19 vaccination drive globally was supposedly a game-changing event. However, the emerging variants of the virus and waning immunity over time posed new challenges for breakthrough infections. Standing at the frontline of defense against COVID-19, healthcare personnel (HCP) were vulnerable to such infections. Aims: This study estimates i) the vaccine breakthrough infections (VBI) among HCP following exposure to COVID-19 cases, and ii) the mean interval between the second dose of vaccine and laboratory-confirmed SARS-CoV-2 infection. Materials and Methods: A cross-sectional study was conducted including 385 HCP with a history of exposure to COVID-19 cases during January and February 2022. Demographic details and clinical and vaccination history were collected from the test forms and the Web-based hospital management system. Laboratory testing of COVID-19 was carried out by real-time RT-PCR test. Results: The majority of the HCP were males (262; 68.05%) and nurses (180; 46.75%) by occupation. Two doses of vaccines were received by 278 (87.7%) HCP. VBI was confirmed in 185 (66.55%) HCP. No significant difference in VBI between the COVAXIN and COVISHIELD recipients (P = 0.69) was observed. The interval between the second dose and confirmed SARS-CoV-2 infection was significantly higher (P < 0.00001) in COVAXIN recipients (median 228 days) than in COVISHIELD recipients (median 95 days). Conclusions: The incidence of VBI was very high among the HCP, but not statistically different among the COVAXIN and COVISHIELD-recipients. Waning immunity over time suggests boosting immunity with a third dose because of emerging variants.

Effect of Metformin on Plasma Exposure of Rifampicin, Isoniazid, and Pyrazinamide in Patients on Treatment for Pulmonary Tuberculosis.

BACKGROUND: To evaluate the effect of metformin on the plasma levels of rifampicin, isoniazid, and pyrazinamide in patients with drug-sensitive pulmonary tuberculosis being treated with first-line antituberculosis treatment (ATT) and to assess the influence of gene polymorphisms on the metabolic pathway of metformin and plasma levels of antitubercular drugs. METHODS: Nondiabetic adults aged 18-60 years with pulmonary tuberculosis were randomized to either the standard ATT (ATT group) or ATT plus metformin (METRIF group) groups in a phase IIB clinical trial. An intensive pharmacokinetic study with blood collection at 0 hour (predosing), followed by 1, 2, 4, 6, 8, and 12 hours after dosing was conducted during the first month of treatment in a subset of 60 study participants after a minimum of 14 doses. Plasma concentrations of rifampicin, isoniazid, pyrazinamide, and metformin were measured by high-performance liquid chromatography using validated methods, and pharmacokinetic parameters and OCT1 and MATE1 gene polymorphisms were compared between the groups. RESULTS: Significant increases in the clearance of rifampicin, isoniazid, and pyrazinamide were observed in patients in the METRIF group (n = 29) compared with those in the ATT group (n = 31). The AA genotypes of the single-nucleotide polymorphism of rs2289669 (MATE1) in the METRIF group showed a significantly decreased area under the concentration-time curve to the last observation point and increased clearance of rifampicin. CONCLUSIONS: Metformin altered rifampicin and isoniazid plasma concentrations in patients receiving antituberculosis treatment for pulmonary tuberculosis with little effect on sputum conversion at the end of treatment. Studies with larger sample sizes are needed to understand host drug-drug interactions.

GeneXpert Ultra in Urine Samples for Diagnosis of Extra-Pulmonary Tuberculosis.

Extra-pulmonary tuberculosis (EPTB) continues to be difficult to diagnose. Novel biomarkers in biological specimens offer promise. Detection of Mycobacterium tuberculosis (Mtb) DNA in urine could prove useful in diagnosis of EPTB, possibly due to disseminated disease or micro-abscesses reported in kidneys. The current study was designed to detect Mtb DNA in stored urine samples from patients with EPTB. Diagnosis of EPTB was reached using Microbiological Reference Standards (MRS) on samples from the disease site using WHO Recommended Diagnostics (WRD), [smear microscopy, liquid culture (MGIT-960)] and GX (molecular WRD, mWRD) and Comprehensive reference standards [CRS, clinical presentation, microbiological reference standards, radiology, histopathology]. GX-Ultra was performed on urine samples stored in -80oC deep freezer, retrospectively. Of 70 patients, 51 (72.9%) were classified as confirmed TB, 11 (15.7%) unconfirmed TB, and 8 (11.4%) unlikely TB. GX-Ultra in urine samples demonstrated sensitivity of 52.9% and specificity of 57.9% against MRS, and higher sensitivity of 56.5% and specificity of 100% against CRS. The sensitivity and specificity of GX-Ultra in urine was 53.6% and 75% for pus sample subset and 52.2% and 53.3% for fluid sample subset. Urine being non-invasive and easy to collect, detection of Mtb DNA using mWRD in urine samples is promising for diagnosis of EPTB.

A strip-based assay for detection of CrfA enzyme activity to differentiate Mycobacterium tuberculosis and non-tuberculous mycobacteria.

There is an unmet need for tools that permit diagnosis of Tuberculosis (TB) that are affordable, low-tech, and can differentiate Mycobacterium tuberculosis (M.tb) from non-tuberculous mycobacteria (NTM). In this study, we have developed a strip-based assay to detect the activity of a unique Carbapenem Resistance Factor A (CrfA) enzyme present only in M.tb. The strip comprises of PVDF (Polyvinylidene fluoride) membrane that has an immobilized anti-CrfA antibody to capture the CrfA enzyme from M.tb lysate. Lysate of mycobacteria is applied to the strip, washed, and incubated in the presence of chromogenic reporter dye which is a substrate for CrfA. A change in the color of the dye that is readily visible to the naked eye is the readout. We evaluated lysates from M.tb and various NTMs namely, M. abscessus, M. chelonae, M. avium, M. obuense, M. paraintracellulare, M. kansasi, including the patient-derived sputum samples. The strip assay selectively identified only those samples containing M.tb. Based on this evidence, this new assay enables the identification and differentiation of M.tb from NTMs in patient sputum samples. As this tool can be simple to use, therefore has the potential to serve the unmet need for diagnosis of TB and NTM infections in resource-limited settings.

Phylogeny and evolution of SARS-CoV-2 during Delta and Omicron variant waves in India.

SARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India. Delta variant was reported in patients without comorbidity (97%), while Omicron BA.2 was reported in patients with comorbidity (77%). Tissue adaptation studies brought forth higher propensity of Omicron variants to bronchial tissue than lung, contrary to observation in Delta variants from Delhi. Study of codon usage pattern distinguished the prevalent variants, clustering them separately, Omicron BA.2 isolated in February grouped away from December strains, and all BA.2 after December acquired a new mutation S959P in ORF1b (44.3% of BA.2 in the study) indicating ongoing evolution. Loss of critical spike mutations in Omicron BA.2 and gain of immune evasion mutations including G142D, reported in Delta but absent in BA.1, and S371F instead of S371L in BA.1 could explain very brief period of BA.1 in December 2021, followed by complete replacement by BA.2. Higher propensity of Omicron variants to bronchial tissue, probably ensured increased transmission while Omicron BA.2 became the prevalent variant possibly due to evolutionary trade-off. Virus evolution continues to shape the epidemic and its culmination.Communicated by Ramaswamy H. Sarma.

Laparoscopic evaluation of female genital tuberculosis in infertility: An observational study.

Background & objectives: Female genital tuberculosis (FGTB) is an important variety of extrapulmonary TB causing significant morbidity, especially infertility, in developing countries like India. The aim of this study was to evaluate the laparoscopic findings of the FGTB. Methods: This was a cross-sectional study on 374 cases of diagnostic laparoscopy performed on FGTB cases with infertility. All patients underwent history taking and clinical examination and endometrial sampling/biopsy for acid-fast bacilli, microscopy, culture, PCR, GeneXpert (only last 167 cases) and histopathological evidence of epithelioid granuloma. Diagnostic laparoscopy was performed in all the cases to evaluate the findings of FGTB. Results: Mean age, parity, body mass index and duration of infertility were 27.5 yr, 0.29, 22.6 kg/m2 and 3.78 years, respectively. Primary infertility was found in 81 per cent and secondary infertility in 18.18 per cent of cases. Endometrial biopsy was positive for AFB microscopy in 4.8 per cent, culture in 6.4 per cent and epithelioid granuloma in 15.5 per cent. Positive peritoneal biopsy granuloma was seen in 5.88 per cent, PCR in 314 (83.95%) and GeneXpert in 31 (18.56%, out of last 167 cases) cases. Definite findings of FGTB were seen in 164 (43.86%) cases with beaded tubes (12.29%), tubercles (32.88%) and caseous nodules (14.96%). Probable findings of FGTB were seen in 210 (56.14%) cases with pelvic adhesions (23.52%), perihepatic adhesions (47.86%), shaggy areas (11.7%), pelvic adhesions (11.71%), encysted ascites (10.42%) and frozen pelvis in 3.7 per cent of cases. Interpretation & conclusions: The finding of this study suggests that laparoscopy is a useful modality to diagnose FGTB with a higher pickup rate of cases. Hence it should be included as a part of composite reference standard.

Expedited diagnosis of pediatric tuberculosis using Truenat MTB-Rif Dx and GeneXpert MTB/RIF.

Rapid, cost-effective, and sensitive diagnostic assays are essential for global tuberculosis (TB) control, especially in high TB burden, resource-limited settings. The current study was designed to evaluate diagnostic accuracy of Truenat MTB-Rif Dx (MolBio) in children less than 18 years of age, with symptoms suggestive of TB. Gastric aspirate, induced sputum, and broncho-alveolar lavage samples were subjected simultaneously to AFB-smear, GeneXpert MTB/RIF, liquid culture (MGIT-960) and Truenat MTB-Rif Dx. The index-test results were evaluated against microbiological reference standards (MRS). Truenat MTB-Rif Dx had a sensitivity of 57.1%, specificity of 92% against MRS. The sensitivity and specificity of the Truenat MTB-RIF Dx compared with liquid culture was 58.7% and 87.5% while GeneXpert MTB/RIF was 56% and 91.4%. The performance of both GeneXpert MTB/RIF and Truenat MTB-Rif Dx are comparable. Result of our study demonstrates that Truenat MTB-Rif can aid in early and efficient diagnosis of TB in children.

An evaluation of Composite Reference Standard (CRS) for diagnosis of Female Genital Tuberculosis.

BACKGROUND: Female genital tuberculosis (FGTB) is a common cause of infertility in developing countries. Its diagnosis is difficult due to its paucibacillary nature, with no single test having high sensitivity and specificity. This study is to share the experience of using Composite Reference Standard (CRS) for the diagnosis of FGTB. METHODS: This is a prospective study conducted between September 2017 to June 2019, over 100 infertile females found to have FGTB on composite reference standard which consisted of acid-fast bacilli on microscopy or culture, histopathological evidence of epithelioid granuloma, positive gene Xpert on endometrial sample or definite or probable finding of FGTB on laparoscopy. RESULTS: A total of 100 infertile women (78% primary, 22% secondary) found to have FGTB on CRS were enrolled in this study. Mean age, body mass index, parity and duration of infertility were 28.2 years, 23.17 kg/m2, 0.24 ± 0.12 and 2.41 years respectively. Various symptoms were scanty menses (16%), irregular cycle (7%), dysmenorrhea (11%), pelvic pain (11%). Various signs were vaginal discharge (65%), adnexal mass (6%), tubo-ovarian mass on ultrasound (15%), abnormal hysterosalpingography findings (57.14%), positive polymerase chain reaction test (65%) and abnormal hysteroscopy (82.2%). The positive findings on CRS were positive AFB on microscopy or culture (3%), positive gene Xpert (28%) (done in some cases), epithelioid granuloma on histopathology (13%), definite findings on laparoscopy like tubercles, caseous nodules and beaded tubes in (57.19%) patients while probable findings of FGTB like straw colored fluid in POD, extensive dense pelvic, peri-tubal, peri-ovarian adhesions; hydrosalpinx; tubo-ovarian mass; thick fibrosed tubes; mid tubal block; peri hepatic adhesions (Fitz Hugh Curtis Syndrome); hyperemia of tubes/blue uterus on chromotubation were seen in (48.8%) patients. All patients found to be positive on CRS were given 6 months of anti-tubercular therapy. CONCLUSION: This study demonstrates the high reliability of use of composite reference standard for diagnosis of FGTB.

Evaluation of implantation markers and immune cell infiltration in endometrial biopsy of female genital tuberculosis.

BACKGROUND: Female genital tuberculosis (FGTB) causes infertility in a significant number of females. The immunological impact of tuberculosis on endometrium in infertile females has not been studied before. The present study was designed to evaluate markers related to infiltrating immune cells and implantation in endometrial aspiration from infertile females and correlate with conventional tests and polymerase chain reaction (PCR) for tuberculosis (TB). METHODS: It was a prospective cohort study with 385 patients out of which IHC was done in 306 over a period of 3 years from 2013 to 2016 in a tertiary care hospital. Women with infertility, 20-35 years of age, without history of pulmonary TB or intake of antitubercular therapy were included. Endometrial samples were subjected to PCR for TB along with microbiological and histological examination for TB. Immunohistochemistry for CD45, CD3, CD20, CD4, CD8, CD68, CD138, Interferon gamma, Interleukin 10 (IL-10) and implantation markers MUC1 and Notch 1 were done on the endometrial samples along with 25 control subjects. RESULTS: Conventional tests for tuberculosis like staining for acid fast bacilli (AFB), granuloma on histology or culture positivity were seen in 2.61% (6/306; 1.96% had granulomas, 1/306; 0.32% was AFB positive, 2/306; 0.6% were liquid culture positive). PCR was positive in 190/306 (62.09%). CD3, CD20, CD45, CD68, CD4, CD8 and CD 138 expressing infiltrating cells were not significantly related to PCR positive cases. Interferon gamma expressing lymphocytes were significantly higher (38.94%) in PCR positive endometria compared to 26.72% in the PCR negative (p = 0.04). Notch -1 expression correlated significantly with the occurrence of pregnancy. A trend towards high intensity expression of Notch1 was seen in PCR negative cases. MUC-1 expression did not correlate with pregnancy although interferon gamma expression was significantly related to low intensity MUC1 expression. CONCLUSIONS: Immunohistochemical markers are not reliable tests in diagnosis of FGTB. Notch 1 expression though showing correlation with pregnancy has to be further evaluated with a panel of other implantation markers. STUDY FUNDING: Indian Council of Medical Research, New Delhi, India.

Role of Magnetic Resonance Imaging in evaluation of tuberculous tubo ovarian mass.

OBJECTIVE: Role of Magnetic Resonance Imaging (MRI) in diagnosis of tuberculous tubo-ovarian (TO) mass. METHODS: MRI was performed on 33 patients of tuberculous TO mass of female genital tuberculosis (FGTB). RESULTS: Mean age, BMI, and parity was 27.5 ± 4.2 years, 22.7 ± 3.6 kg/m2, and 0.27 ± 0.13. All patients (100%) had infertility; primary infertility (72.72%) and secondary infertility (27.23%) with mean 5.8 years. Abdominal/pelvic pain 33 (100%) cases, abdominal lump 4 (12.12%), adnexal mass 33 (100%). MRI findings showed pelvic masses 33 (100%), bilateral TO masses 11 (33.33%), cystic lesion 4 (12.12%), solid cystic lesion 3 (9.09%) with bilateral pyosalpinx 1 (3.3%), homogeneous content with ascites 1 (3.03%), rim enhancing lesion abutting pelvic wall in 1 (3.03%). Right adnexal mass 11 (33.33%), right adnexal cyst 2 (6.06%), right adnexal cystic mass in 1 (3.03%), right sided complex TO mass 1 (3.03%), right sided hydrosalpinx in 1 (3.03%) case, right sided TO mass in 4 (12.12%) cases and right sided para-ovarian cyst in 2 (6.06%). Left sided adnexal mass was seen in 11 (33.33%), cystic lesion in 1 (3.03%), ovarian cyst in 3 (9.09%) cases, left sided hydrosalpinx in 2 (6.06%), left ovarian cyst 2 (6.06%) cases, left sided ovarian cyst with encysted ascites 1 (3.03%) case and with left sided paraovarian cyst 2 (6.06%) case. Miscellaneous finding were generalised ascites (6.06%), encysted ascites (3.03%), pelvic (1; 3.03%) and mesenteric lymphadenopathy 1 (3.03%). Incidental finding were fibroid 3 (9.09%) and adenomyosis 1 (3.03%) case. CONCLUSION: MRI appears to be useful diagnostic modality for tuberculous TO masses where differential diagnosis is malignancy but molecular diagnosis remains the gold standard.

Efficacy of Bacillus Calmette-Guérin (BCG) Vaccination in Reducing the Incidence and Severity of COVID-19 in High-Risk Population (BRIC): a Phase III, Multi-centre, Quadruple-Blind Randomised Control Trial.

INTRODUCTION: Universal coverage of vaccines alone cannot be relied upon to protect at-risk populations in lower- and middle-income countries against the impact of the coronavirus disease 2019 (COVID-19) pandemic and newer variants. Live vaccines, including Bacillus Calmette-Guérin (BCG), are being studied for their effectiveness in reducing the incidence and severity of COVID-19 infection. METHODS: In this multi-centre quadruple-blind, parallel assignment randomised control trial, 495 high-risk group adults (aged 18-60 years) were randomised into BCG and placebo arms and followed up for 9 months from the date of vaccination. The primary outcome was the difference in the incidence of COVID-19 infection at the end of 9 months. Secondary outcomes included the difference in the incidence of severe COVID-19 infections, hospitalisation rates, intensive care unit stay, oxygen requirement and mortality at the end of 9 months. The primary analysis was done on an intention-to-treat basis, while safety analysis was done per protocol. RESULTS: There was no significant difference in the incidence rates of cartridge-based nucleic acid amplification test (CB-NAAT) positive COVID-19 infection [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.54-2.14] in the two groups, but the BCG arm showed a statistically significant decrease in clinically diagnosed (symptomatic) probable COVID-19 infections (OR 0.38, 95% CI 0.20-0.72). Compared with the BCG arm, significantly more patients developed severe COVID-19 pneumonia (CB-NAAT positive) and required hospitalisation and oxygen in the placebo arm (six versus none; p = 0.03). One patient belonging to the placebo arm required intensive care unit (ICU) stay and died. BCG had a protective efficacy of 62% (95% CI 28-80%) for likely symptomatic COVID-19 infection. CONCLUSIONS: BCG is protective in reducing the incidence of acute respiratory illness (probable symptomatic COVID-19 infection) and severity of the disease, including hospitalisation, in patients belonging to the high-risk group of COVID-19 infection, and the antibody response persists for quite a long time. A multi-centre study with a larger sample size will help to confirm the findings in this study. CLINICAL TRIALS REGISTRY: Clinical Trials Registry India (CTRI/2020/07/026668).

The Bacillus Calmette­Guérin (BCG) vaccine has been studied previously in several settings, including reducing childhood mortalities due to viral infections and induction of trained immunity and reducing upper respiratory tract infections and pneumonia in older adults. This multi-centre trial has tried to evaluate the efficacy of BCG revaccination in reducing the incidence and severity of COVID-19 infections in adults between 18 and 60 years of age belonging to the high-risk group owing to the presence of comorbidities including diabetes, chronic kidney disease, chronic liver disease and chronic lung diseases. A single dose of BCG vaccine produced significantly high titres of BCG antibodies lasting for six months. While there was no significant reduction in the incidence of COVID-19 infection, there was an 8.4% reduction in the incidence of symptomatic COVID-19 disease at the end of 9 months of follow-up. In addition, there were significantly fewer severe COVID-19 infections requiring hospital stay and oxygen support. However, the overall numbers of severe COVID-19 infections were low. Thus, the study shows that BCG can protect against symptomatic and severe COVID-19 disease. However, it might not reduce the incidence of new infections. The study results are significant for low- and middle-income countries without adequate coverage of primary doses of COVID-19 vaccination, let alone the booster doses. Future studies should evaluate the BCG vaccine's efficacy as a booster compared with routine COVID-19 vaccine boosters.

A rare case of complicated pancreatitis due to leptospirosis.

The COVID-19 pandemic and the actions taken to combat it have greatly impacted the health infrastructure of all nations. Here we present a rare case of leptospirosis with severe acute pancreatitis, bilateral peripheral gangrene, disseminated intravascular coagulopathy and multiorgan failure. This is a rare presentation of leptospirosis wherein the patient had no history suggestive of acquisition of leptospires. The patient was started on doxycycline but still could not be saved due to the multisystem involvement.

Persistence of SARS-CoV-2 in COVID-19 patients during the second wave of the pandemic in India.

INTRODUCTION: India witnessed the catastrophic second wave of COVID-19 during the summer months of 2021. Many patients with non-resolution of symptoms admitted to dedicated COVID-19 treatment centers required prolonged inpatient care which led to the unavailability of beds for other COVID-19 patients. The objective of this study was to determine the duration of SARS-CoV-2 positivity in moderate and severe COVID-19 patients requiring long-term pulmonary care as well as to find out the association between different variables with the persistence of the virus. METHODOLOGY: A retrospective chart review of clinical and laboratory data of patients with moderate and severe COVID-19 between 1st April 2021 and 15th July 2021 admitted for more than 28 days and requiring long-term pulmonary care was carried out at National Cancer Institute, AIIMS, India. SARS-CoV-2 RNA was detected with real-time reverse transcriptase-polymerase chain reaction-based tests. Data from all consecutively included patients satisfying the selection criteria were presented temporally and analyzed by Fisher's exact test (p < 0.05). RESULTS: All 51 patients tested positive for SARS-CoV-2 RNA at the 5th week of initial laboratory confirmation of COVID-19. The majority of the patients (38; 74.5%) remained positive for viral RNA till the 6th week and the median duration of viral positivity was 45 days. The clinical presentation of SARI at admission was significantly higher among patients with viral persistence till the 6th week (p < 0.05). CONCLUSIONS: The median duration of the viral positivity was 45 days and SARI at admission was significantly associated with viral persistence till the 6th week.

2D-DIGE based urinary proteomics and functional enrichment studies to reveal novel Mycobacterium tuberculosis and human protein biomarker candidates for pulmonary tuberculosis.

In the absence of a sensitive and specific diagnostic modality capable of detecting all forms of tuberculosis (TB), proteomics may identify specific Mycobacterium tuberculosis (M.tb) proteins in urine, with a potential as biomarkers. To identify candidate biomarkers for TB, proteome profile of urine from pulmonary TB patients was compared with non-disease controls (NDC) and disease controls (DC, Streptococcus pneumonia infected patients) using a combination of two-dimensional difference gel electrophoresis (2D-DIGE) and liquid chromatography tandem mass spectrometry (LCMS/MS). Eleven differentially expressed host proteins and Eighteen high abundant M.tb proteins were identified. Protein-protein interactome (PPI) and functional enrichment analyses like Gene Ontologies, Reactome pathway etc. demonstrated that the human proteins mainly belong to extracellular space and show physiological pathways for immune response and hematological disorders. Whereas, M.tb proteins belong to the cell periphery, plasma membrane and cell wall, and demonstrated catalytic, nucleotide binding and ATPase activities along with other functional processes. The study findings provide valuable inputs about the biomarkers of TB and shed light on the probable disease consequences as an outcome of the bacterial pathogenicity.

Aspergilloma Morphology on Computed Tomography Angiography and its Clinical Impact in Patients of Haemoptysis.

Amongst various manifestations of pulmonary aspergillosis, chronic pulmonary aspergillosis (CPA) is the most common. We conducted this study to identify different morphological forms of CPA, on computed tomography angiography (CTA), and to correlate these with clinical presentation, as well as, associated imaging features. The study design was cross-sectional, with a final sample size of 65 patients, recruited over a period of 2years from January 2017 to October 2018. Patients with past history of tuberculosis (TB), presenting with haemoptysis and found to have aspergilloma on computed tomography and lab tests were included in the study. All patients underwent CTA for evaluation of haemoptysis. Three morphological types of intracavitary aspergilloma on imaging were identified: type 1-nodular soft tissue along the cavity-wall, type-2 soft tissue density with multiple air lucencies and type-3 homogenous soft tissue opacity with air-crescent sign. Aspergilloma types were correlated with grade and duration of haemoptysis, associated imaging findings and vascularity score on CTA. Mean age of the patients was 40.97 +/- 13.69 years. As the type of aspergilloma changed from 1 to 3, there was a decrease in cavity wall thickness, peri-cavitary inflammation and vascularity. It is the type 1 and 2 aspergillomas, which caused more inflammation in the lungs, and hence recruited more abnormal vasculature. No significant correlation was found between haemoptysis severity and type of aspergilloma; type 3 aspergilloma however had longer duration of haemoptysis. In conclusion, the initial stages of formation of aspergilloma (type 1 and 2) cause more parenchymal inflammation and symptoms. The classical Monod sign is observed in the late stage of aspergilloma, since the peri-cavitary inflammation is reduced by then and thus the symptoms.

Scrub typhus in two COVID-19 patients: a diagnostic dilemma.

The authors describe a case series of co-infection with COVID-19 and scrub typhus in two Indian patients. Clinical features like fever, cough, dyspnea and altered sensorium were common in both patients. Case 1 had lymphopenia, elevated IL-6 and history of hypertension, while case 2 had leukocytosis and an increased liver enzymes. Both patients had hypoalbuminemia and required admission to the intensive care unit; one of them succumbed to acute respiratory distress syndrome further complicated by multiple organ dysfunction syndrome. Seasonal tropical infections in COVID-19 patients in endemic settings may lead to significant morbidity and mortality. Therefore, high clinical suspicion and an early diagnosis for co-infections among COVID-19 patients are essential for better patient management.