Background Scrub typhus, a vector-borne zoonotic infection caused by the bacteria Orientia tsutsugamushi, is one of the most common and clinically important rickettsial infections worldwide. An estimated one million cases occur annually with a high case fatality rate. Although scrub typhus is a major public health threat in India, the burden and distribution remains unclear. We aimed to estimate the burden of scrub typhus in India. Methodology We performed a systematic review of published literature on scrub typhus from India to extract information on epidemiology, morbidity, and mortality. Important databases were searched using keywords and appropriate combinations. We identified observational, interventional, and population-based studies and extracted the data to evaluate the number of cases diagnosed using serology or PCR and the number of deaths due to scrub typhus. We conducted a systematic narrative synthesis to summarize included studies. Principal findings In the last decade, there were 18,781 confirmed scrub typhus cases reported in 138 hospital-based studies and two community-based studies. IgM ELISA was used in 122 studies to confirm the cases in majority (89%). The proportion of scrub typhus among acute undifferentiated febrile illness (AUFI) studies was 25.3%, and community seroprevalence was 34.2%. Ninety studies had data published on multiple organ involvement out of which 17.4% of cases had multiple organ dysfunction syndromes, 20.4% patients required ICU admission, and 19.1% needed ventilation. The overall case-fatality rate was 6.3%, and the mortality among those with multi-organ dysfunction syndrome was as high as 38.9%. Conclusion/significance Scrub typhus, a common acute febrile illness in India causing severe morbidity, accounts for a large number of deaths. The burden of the disease has been underappreciated. Early diagnosis and prompt treatment can significantly reduce complications and mortality. Establishing good surveillance and instituting appropriate control measures are urgently needed.

This study assessed the risk factors driving the epidemic of COVID-19 associated mucormycosis (COVID-Mucor) in Indiathat accompanied the COVID-19 pandemic, particularly the second wave. We analysed the risk factors among 164 participants:132 COVID-Mucor(cases) and 32 non-COVID-Mucor(controls)using the data from a prospective cohort study of mucormycosis over oneyear. Diabetes mellitus remained a pivotal risk factor in both groups (97%) while uncontrolled diabetes mellitus (OR: 4.6; p=0.026)and newly detected diabetes (OR: 3.3; p=0.018), werecommoneramong the cases. Most patients with COVID-Mucor had mild COVID-19. Steroid use, often unwarranted, was highly associated with COVID-Mucorafter adjusting for other risk factors (OR 28.4; P 0.001). Serum ferritin was significantly higher(p=0.041), while C-reactive protein was not, suggesting that alterations in iron metabolism probably predispose to COVID-Mucor. Oxygen was used only in a small minority of patients with COVID-Mucor. The in-hospital mortality in both groups was low. In conclusion, the Indian COVID-Mucorepidemic was likely driven by a convergence of interlinked risk factors –uncontrolled diabetes mellitus, unwarranted steroid use, and perhapsCOVID-19 itself. Appropriate steroid use in patients with severe COVID-19 and screening and optimal control of hyperglycaemia can prevent COVID-Mucor.

A significant proportion of patients with Rhino-orbito-cerebral mucormycosis (ROCM) develop oroantral fistulas. Due to the unclear efficacy of crushed delayed-release posaconazole tablets (DRPT) via nasogastric tube in this group of patients, clinicians often use inferior alternatives like posaconazole suspension. In this prospective study, we report good plasma concentrations (median, 2,639 ng/mL; interquartile range [IQR], 1,690 to 3,575 ng/mL; and range, 1,004 to 4,835ng/mL) and complete cure and survival at 3 and 6 months in 19 such patients.

Background Few treatment options exist for patients with severe central nervous system tuberculosis (CNS TB) worsening due to inflammatory lesions, despite optimal antitubercular therapy (ATT) and steroids. Data regarding the efficacy and safety of infliximab in these patients is sparse. Methods We performed a matched retrospective cohort study based on Medical Research Council (MRC) grading system and modified Rankin Scale (mRS) scores comparing two groups of adults with CNS TB. Cohort-A received at least one dose of infliximab after optimal ATT and steroids, between March, 2019 to July, 2022. Cohort-B received only ATT and steroids. Disability-free survival, [(mRS) score ≤2] at 6-months was the primary outcome. Results Baseline MRC grades and mRS scores were similar between the cohorts. Median duration from the start of ATT and steroids to infliximab treatment was 6 (IQR 3.7-13) months, and neurological deficits was 4 (IQR 2-6.2) months. Indications for infliximab were symptomatic tuberculomas (20/30; 66.7%), spinal cord involvement with paraparesis [8/30; 26.7%] and optochiasmatic arachnoiditis (3/30; 10%), worsening despite adequate ATT and steroids. Severe disability (5/30; 16.7% and 21/60; 35%) and all-cause mortality (2/30; 6.7% and 13/60; 21.7%) at 6-months were lower in Cohort-A. In the combined study population, only exposure to infliximab was positively associated (aRR 6.2, p=0.001, 95% CI 2.18-17.83) with disability-free survival at 6-months. There were no clear infliximab related side effects noted. Conclusion Infliximab may be an effective and safe adjunctive strategy among severely disabled patients with CNS TB, not improving despite optimal ATT and steroids. Adequately powered phase-3 clinical trials are required to confirm these early findings.

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