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The emergence of newer variants with the immune escape potential raises concerns about breakthroughs and re-infections resulting in future waves of infection. We examined the protective effect of prior COVID-19 disease and vaccination on infection rates among a cohort of healthcare workers (HCW) in South India during the second wave driven mainly by the delta variant. Symptomatic HCWs were routinely tested by RT-PCR as per institutional policy. Vaccination was offered to all HCWs in late January, and the details were documented. We set up a non-concurrent cohort to document infection rates and estimated protective efficacy of prior infection and vaccination between 16th Apr to 31st May 2021, using a Cox proportional hazards model with time-varying covariates adjusting for daily incidence. Between June 2020 and May 2021, 2735 (23.9%) of 11,405 HCWs were infected, with 1412, including 32 re-infections, reported during the second wave. 6863 HCWs received two doses of vaccine and 1905 one dose. The protective efficacy of prior infection against symptomatic infection was 86.0% (95% CI 76.7%-91.6%). Vaccination combined with prior infection provided 91.1% (95% CI 84.1%-94.9%) efficacy. In the absence of prior infection, vaccine efficacy against symptomatic infection during the second wave was 31.8% (95% CI 23.5%- 39.1%). Prior infection provided substantial protection against symptomatic re-infection and severe disease during a delta variant driven second wave in a cohort of health care workers.

Progressive multifocal leukoencephalopathy (PMLE) is caused by severe cortical demyelination due to reactivation of the polyomavirus, JC virus in profound immunosuppression, like advanced HIV infection. Cerebellum-predominant PMLE is rare and underreported. We report seven patients with confirmed cerebellum-predominant PMLE from a quaternary care center in South India over a five-year period. We report their outcomes and disability using modified Rankin scores (mRS). All seven patients had advanced HIV infection with low CD4 counts [median (IQR) 79 (51-155) cells/μL]. Ataxia (5/7; 71.4%), dysarthria (4/7; 57.1%), and vertigo (2/7; 28.5%) were the common symptoms at presentation. Cerebellar hemisphere or cerebellar peduncles with or without brainstem involvement were noted in all patients. Concomitant supratentorial involvement was also present in six patients. 'Shrimp sign' was seen in five of the seven patients. Only one patient had significant neurological recovery on follow-up. Cerebellum predominant PMLE is a severe, disabling opportunistic infection among patients with advanced HIV infection.

Paradoxical reactions (PRs) are poorly studied complex immunological phenomena, among patients with tuberculosis (TB). When PRs involves critical structures like the central nervous system (CNS), immunomodulatory therapy is often required. Predictors for PRs in TB to pre-empt appropriate treatment strategies in high-risk groups are lacking. TT genotype of Leukotriene A4 hydrolase ( LTA4H ) promoter region rs17525495 polymorphisms are associated with exaggerated immune responses in Tuberculous meningitis (TBM), the most severe form of extrapulmonary tuberculosis (EPTB). The association of these polymorphisms with PRs is not known. We evaluated this plausibility among 113 patients with EPTB, at high risk of PRs. Majority [81 (71.7%)] had disseminated tuberculosis with prominent CNS [54 (47.8%)] and lymph node involvement [47 (41.6%)]. Human immunodeficiency Virus (HIV) co-infection was seen among 23 (20.3%) patients. PRs were noted in 38.9% patients, at a median duration of 3 months (IQR 2–4). LTA4H rs17525495 single nucleotide polymorphism (SNP) analysis showed 52 (46%) patients had CC, 43 (38.1%) had CT and 18 (15.9%) had TT genotypes. There was no statistically significant difference in occurrence [CC 38.5% vs CT 39.5% vs TT 38.7%] and time of onset [median (IQR)] of PRs across the genotypes [CC 3 (1–4.7), CT 3 (2–5), TT 2 (2–3)]. PRs was shown to be significantly linked with HIV co-infection (RR 0.6, 95% CI 0.29–1.28), culture positivity (RR 0.5, 95% CI 0.28–1.14), TB Lymphadenitis (RR 0.7, 95% CI 0.44–1.19) and CNS involvement RR 2.1, 95% CI 1.27–3.49) in the univariate analysis (p < 0.2). On multivariate analysis, CNS involvement alone was associated with PRs (aRR 3.8 (1.38–10.92); p < 0.01). PRs were associated with CNS involvement but not with LTA4H rs17525495 polymorphisms.

Prospective and sequential evaluation of homeostatic changes leading to thrombosis across COVID 19 disease severity spectrum are limited. In this prospective observational study, haemostasis was evaluated in patients with mild, moderate-severe, and critical COVID-19 infection. Markers of endothelial activation [Soluble thrombomodulin (sTM), von Willebrand Factor (VWF)], platelet activation [Soluble P-selectin, beta-thromboglobulin (BTG)] and global haemostasis [Rotational thromboelastometry (ROTEM)] were evaluated on days 1 and 5 after admission. The study cohort comprised of 100 adult patients (mild = 20, moderate-severe = 22, critical = 58). Sixty-five patients received anticoagulation for 10 (7–14) days. Thrombotic events were seen in 9 patients. In-hospital mortality was 21%. Endothelial activation markers were elevated at baseline in all subgroups, with levels in moderate-severe (sTM = 4.92 ng/ml, VWF = 295 U/dl) [reference-ranges: sTM = 2.26–4.55 ng/ml; Soluble P-selectin = 13.5–31.5 ng/ml; BTG = 0.034–1.99 ng/ml] and critical patients (sTM = 6.07 ng/ml, VWF = 294 U/dl) being significantly higher than in the mild group (sTM = 4.18 ng/ml, VWF = 206 U/dl). In contrast, platelet activation markers were elevated only in critically ill patients at baseline (Soluble P-selectin = 37.3 ng/ml, BTG = 2.51 ng/ml). The critical group had significantly lower fibrinolysis on days 1 and 5 when compared with the moderate-severe arm. COVID-19 infection was associated with graded endothelial activation and lower fibrinolysis that correlated with illness severity.

Background The role and performance of various serological tests for the diagnosis of COVID-19 are unclear. This study aimed to evaluate the performance of seven commercially available serological assays for SARS-CoV-2 antibodies by testing COVID-19 cases and controls. Methods Adult patients with fever for > 5 days, admitted to a tertiary-care teaching hospital in South India, were enrolled prospectively between June and December 2020. SARS-CoV-2 RT-PCR confirmed patients were classified as cases, and patients with febrile illness with laboratory-confirmed alternative diagnosis and healthy participants were controls. All participants were tested with SCoV-2 Detect ™ IgM ELISA kit and SCoV-2 Detect ™ IgG ELISA kit (InBios International, Seattle, USA) (Inbios), SARS-CoV-2 Total and SARS-CoV-2 IgG (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) (Siemens), Roche Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics, Rotkreuz, Switzerland) (Roche), Abbott SARS-CoV-2 IgG (Abbott Diagnostics, IL, USA) (Abbott), and Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorinS.p.A., Saluggia, Italy) (Liaison). The sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV), and accuracies were compared. Results There were 303 participants: 153 cases and 150 controls. ELISA detecting anti-S protein antibody was more sensitive (88.9% for IgG and 86.3% for IgM) than the CLIAs (82.4% for total antibodies and 76.5–85.6% for IgG). Among CLIAs, Roche IgG was most sensitive (85.6%) followed by Abbott (83%) and Liaison (83%). Abbot had the best PPV (88.8%) and was more specific (89.3%) than Liaison (82%) and Roche (82%). Siemens IgG was less sensitive (76.5%) than Siemens Total (82.4%). The specificity of all the serological assays was modest (75–90%). Antibody test positivity increased with the duration of illness reaching 90% after 10 days of illness. When cases were compared against pre-pandemic controls, the IgG gave excellent specificity (98–100%). For seroprevalence studies, InBios IgG had the best accuracy (90.8%) with 88.9% sensitivity and 97.6% specificity. Conclusion The serological assays are important adjuncts for the diagnosis of COVID-19 in patients with persistent symptoms, especially in the second week of illness. The value of serological diagnostic tests is limited in the first week of illness and they provide additional value in seroprevalence studies. The diagnostic accuracy of the ELISA and CLIA platforms were comparable.

Background Oral human papillomavirus (HPV) infection has been causally linked to a subset of oropharyngeal cancers in Western populations, and both oropharyngeal cancer and oral HPV infection are increased among HIV-positive individuals. India has high incidences of oral and oropharyngeal cancers, and Indian HIV-positive men who have sex with men (MSM) may be at increased risk of developing oropharyngeal cancers. However, there is little information available on the prevalence of oral HPV in this population. Methods We tested 302 HIV-positive Indian MSM for oral HPV infection using L1 HPV DNA PCR with probes specific for 29 types and a mixture of 10 additional types. CD4+ level and plasma HIV viral load (VL) were measured. Participants completed an interviewer-administered questionnaire including a sexual history. Results The prevalence of oral HPV was 23.7% (95% CI: 19–29%) and 2.4% of participants had oncogenic HPV types. No participants had oral HPV type 16 (HPV-16) and the prevalence of other anogenital HPV types was low. Participants with higher CD4+ levels had reduced odds of having any oral HPV infection (OR: 3.1 [1.4–6.9]) in multivariable analyses. Conclusions This is the first report of oral HPV among Indian HIV-positive MSM. Our results show a high prevalence of oral HPV infection consistent with studies from Western populations. However, oncogenic anogenital HPV types were relatively uncommon in our study population. It is unknown what the impact of this distribution of oral HPV will be on oropharyngeal cancers. HIV-positive MSM in India should be monitored closely for oral and oropharyngeal pre-cancer and cancer.

Background: In the COVID-19 pandemic, the frontline health-care workers (HCWs) are at increased risk of acquiring infection either through household or workplace exposure. Objectives: To assess the risk of acquiring infection after COVID-19 exposure, we evaluated the effectiveness of a contact tracing assessment to identify the high-risk contacts. Materials and Methods: All HCW who tested COVID-19 positive in July 2020 were interviewed to do risk assessment based on their exposure, advised quarantine, and then followed up on day 14 for development of symptoms of COVID-19. Results: Contact tracing identified 2569 HCW contacts for 422 index positive cases, among which 1642 (63.9%) were contactable for follow-up. Among 1642 contacts, 12.97% developed COVID-19 symptoms within 14 days of the exposure. Household contacts comprising (142 out of 956, 14.9%) had a higher risk of becoming symptomatic than workplace contacts (71 out of 686, 10.3%) ([odds ratio 0.66 (confidence interval 0.49-0.89)]. Of these, 76.6% of the household exposure and 55.4% of significant workplace exposure were tested positive for COVID-19. Conclusions: Based on the risk assessment, we found that a HCW is likely to acquire infection at home rather than at the workplace, and hence, an appropriate quarantine policy can help decrease the transmission and mitigate staff shortage.

IntroductionInternational guidelines recommend definitive combination antibiotic therapy for the management of serious infections involving carbapenem-resistant Acinetobacter (CRAB) species. The commonly available combination options include high-dose sulbactam, polymyxins, tetracyclines, and cefiderocol. Scanty prospective data exist to support this approach.MethodsPatients with CRAB bacteraemia, ventilator-associated pneumonia (VAP), or both were categorized based on whether they received combination therapy or monotherapy. The 30-day mortality was compared between the two groups. Inverse probability treatment weighting (IPTW) was done using propensity score (PS) for a balanced comparison between groups.ResultsBetween January 2021 and May 2023, of the 161 patients with CRAB bacteraemia (n = 55, 34.2%), VAP (n = 46, 28.6%), or both (n = 60, 37.3%) who received appropriate intravenous antibiotic therapy, 70% (112/161) received monotherapy, and the rest received combination therapy. The overall 30-day mortality was 62% (99/161) and not different (p = 0.76) between the combination therapy (31/49, 63.3%) and monotherapy (68/112, 60.7%) groups. The propensity score matching using IPTW did not show a statistical difference (p = 0.47) in 30-day mortality for receiving combination therapy with an adjusted odds ratio (OR) P of 1.29 (0.64, 2.58).ConclusionCombination therapy for CRAB infections needs further study in a randomised controlled trial, as this observational study showed no difference in 30-day mortality between monotherapy and combination therapy.

Introduction The objective of this study was to examine the evolution of carbapenem-resistant Klebsiella pneumoniae (CRKp) infections and their impact at a tertiary care hospital in South India. Methods A comparative analysis of clinical data from two prospective cohorts of patients with CRKp bacteremia (C1, 2014–2015; C2, 2021–2022) was carried out. Antimicrobial susceptibilities and whole genome sequencing (WGS) data of selected isolates were also analyzed. Results A total of 181 patients were enrolled in the study, 56 from C1 and 125 from C2. CRKp bacteremia shifted from critically ill patients with neutropenia to others (ICU stay: C1, 73%; C2, 54%; p  = 0.02). The overall mortality rate was 50% and the introduction of ceftazidime-avibactam did not change mortality significantly (54% versus 48%; p  = 0.49). Oxacillinases (OXA) 232 and 181 were the most common mechanisms of resistance. WGS showed the introduction of New Delhi metallo-β-lactamase-5 (NDM-5), higher genetic diversity, accessory genome content, and plasmid burden, as well as increased convergence of hypervirulence and carbapenem resistance in C2. Conclusions CRKp continues to pose a significant clinical threat, despite the introduction of new antibiotics. The study highlights the evolution of resistance and virulence in this pathogen and the impact on patient outcomes in South India, providing valuable information for clinicians and researchers.

Retrospective study. To report the prevalence of patients with multidrug-resistant (MDR) tubercular spondylodiscitis and their outcomes. Additionally, to assess the role of Xpert MTB/RIF assay in early detection of MDR tuberculosis. MDR tuberculosis is increasing globally. The World Health Organization (WHO) has strongly recommended Xpert MTB/RIF assay for early detection of tuberculosis. From 2006 to 2015, a retrospective study was conducted on patients treated for MDR tuberculosis of the spine. Only patients whose diagnosis was confirmed using either culture and/or the Xpert MTB/RIF assay were included. Diagnostic method, treatment regimen, time taken to initiate second-line antituberculosis treatment (ATT), drug-related complications, and cost of medications were analyzed. All patients with MDR were treated according to the WHO recommendations for 2 years. The outcome parameters analyzed included clinical, biochemical, and radiological criteria to assess healing status. From 2006 to 2015, a total of 730 patients were treated for tubercular spondylodiscitis. Of those, 36 had MDR tubercular spondylitis (prevalence, 4.9%), and three had extremely drug resistant tubercular spondylitis (prevalence, 0.4%). In this study, 30 patients, with a mean age of 29 years and a mean post-treatment follow-up of 24 months, were enrolled. The majority (77%) had secondary MDR, 17 (56%) underwent surgery, and 26 (87%) completed treatment for 2 years and were healed. Drug-related complications (33%) included ototoxicity, hypothyroidism, and hyperpigmentation of the skin. The average time taken for initiation of second line ATT for MDR patients with Xpert MTB/RIF assay as the diagnostic tool was 18 days, when compared to patients for whom the assay was not available which was 243 days. The prevalence of MDR tubercular spondylodiscitis was 4.9%. In total, 87% of patients were healed with adequate treatment. The sensitivity and specificity of the Xpert MTB/RIF assay to detect MDR was 100% and 92.3%, respectively.