Clinical, laboratory profile and molecular characterization of Orientia tsutsugamushi among fatal scrub typhus patients from Karnataka, India.

BACKGROUND: Scrub typhus is a vector-borne infection caused by the obligate intracellular organism Orientia tsutsugamushi. In some cases, scrub typhus can result in severe complications, multiorgan failure and death. OBJECTIVE: To study the clinical and laboratory profiles of patients who succumbed to scrub typhus. METHODS: A prospective cohort study was conducted from August 2019 through April 2023 on scrub typhus patients admitted to our hospital. Clinical and laboratory parameters of all the patients were recorded, and blood samples were drawn. To confirm scrub typhus, a nested polymerase chain reaction (nPCR) was performed in collected samples. Viable amplicons were sequenced, and phylogenetic analyses were performed to identify infecting genotypes. RESULTS: A total of 261 patients were enrolled. Of these, nine (3.45%) patients succumbed at a median (Interquartile Range) duration of 5 (1.5, 10.5) days after admission. Sepsis with septic shock (9, 100%) and acute kidney injury (AKI) (6, 66%) were noted among the succumbed patients. All the succumbed patients (100%) required intensive care admission, inotropic and ventilatory support. While 5 (55%) patients required dialysis, two (22%) required blood transfusion. Three (33%) patient samples were co-positive for Leptospira IgM, and four (44%) patients had superinfection with Candida tropicalis, multi-drug-resistant (MDR) E. Coli sepsis, pan drug-resistant (PDR) Acinetobacter Baumanii, and Klebsiella pneumoniae. Phylogenetic analysis revealed Orientia tsutsugamushi Japanese Gilliam-variant (JG-v) like (50%), Karp-like (37.5%), and Japanese Gilliam (JG) like (12.5%) strains among succumbed patients. CONCLUSION: Delay in scrub typhus diagnosis can result in severe complications, septic shock, and multisystem organ failure, culminating in death.

Clinical, laboratory, and molecular epidemiology of Orientia tsutsugamushi infection from Southwestern India.

Scrub typhus is a vector borne disease which in a proportion of patients causes multiorgan involvement and death if untreated. Infecting genotype and virulence factors play a role in severity of infection and outcome. The current prospective cohort study was undertaken to elucidate the severity of illness in scrub typhus patients and to identify the circulating genotypes in Karnataka, India. A total of 214 patients of either gender from 9 districts of Karnataka and one patient each from Andhra Pradesh and Kerala, India were enrolled in the study. With a predefined severity criterion, 132 patients were segregated to the severe group. Multi organ involvement was seen in 59 (44.69%) patients. Phylogenetic analysis revealed JG-v like (48.97%), Karp-like (26.53%), JG-like (22.44%), and Kato-like (2.04%) strains in Karnataka. Patients infected with Orientia tsutsugamushi Karp-like strains had respiratory involvement (69.2%), cardiovascular involvement (46.2%) and thrombocytopenia (23.1%) and required higher hospital resource utilization.

Neurological manifestations of Kyasanur Forest disease: a retrospective cohort study from South India.

BACKGROUND: Kyasanur Forest disease (KFD) is a viral zoonotic disease where patients present with febrile illness and haemorrhagic manifestations in the first phase. In a small fraction of patients, the fever may be biphasic. This study aimed to describe the neurological manifestations of patients with KFD in the first and second phases of the illness. METHODS: This is a retrospective cohort study of 297 patients admitted with a molecular diagnosis of KFD from December 2018 to December 2020. The case records of these patients were reviewed for evidence of neurological involvement. RESULTS: A total of 34 (11.5%) patients in the first phase and 16 (36.4%) patients in the second phase had neurological involvement. Altered sensorium, seizures and focal infarcts were common in the first phase, while cerebellar signs and leptomeningeal enhancement were common in the second phase. CONCLUSIONS: Neurological involvement is seen in both phases of KFD. While in the first phase it is a result of possible encephalitis/encephalopathy, the second phase involvement is possibly due to postinfectious cerebellitis or meningitis.

Validation of a Clinical Risk-scoring Algorithm for Scrub Typhus Severity in South India.

BACKGROUND: A clinical risk-scoring algorithm (CRSA) to forecast the scrub typhus severity was developed from two general hospitals in Thailand where patients were classified into three groups-nonsevere, severe, and fatal. In this study, an attempt was made to validate the risk-scoring algorithm for prognostication of scrub typhus severity in India. MATERIALS AND METHODS: This prospective study was conducted at a hospital in South India between November 2017 and March 2019. Patients of scrub typhus were categorized into nonsevere, severe, and fatal according to the CRSA. The patients were also grouped into severe and nonsevere according to the definition of severe scrub typhus which was used as a gold standard. The obtained CRSA score was validated against the classification based on the definition of severe scrub typhus. Receiver operating characteristics (ROC) curve for the scores was plotted and the Youden's index for optimal cutoff was used. RESULTS: A total of 198 confirmed cases of scrub typhus were included in the study. According to the ROC curve, at a severity score ≥7, an optimal combination of sensitivity of 75.9% and specificity of 77.5% was achieved. It correctly predicted 76.77% (152 of 198) of patients as severe, with an underestimation of 10.61% (21 patients) and an overestimation of 12.63% (25 patients). CONCLUSION: In the present study setting, a cutoff of ≥7 for severity prediction provides an optimum combination of sensitivity and specificity. These findings need to be validated in further studies. HOW TO CITE THIS ARTICLE: Gulati S, Chunduru K, Madiyal M, Setia MS, Saravu K. Validation of a Clinical Risk-scoring Algorithm for Scrub Typhus Severity in South India. Indian J Crit Care Med 2021;25(5):551-556.

Clinical and laboratory profile of patients with Kyasanur forest disease: A single-centre study of 192 patients from Karnataka, India.

INTRODUCTION: Kyasanur forest disease (KFD) is a biphasic tick-borne viral fever that is endemic to 16 districts and five states of Southern India. The aim of this study was to describe the clinical/ laboratory manifestations of KFD. MATERIALS AND METHODS: This is a retrospective cohort study of confirmed KFD patients admitted in our hospital between December 2018 and June 2019. The demographic, clinical and laboratory parameters of patients during the first and second phase of illness was recorded in a pre-defined case study form. RESULTS: A total of 192 patients from Karnataka were diagnosed with a mean age of 46.2 ± 15.6 years and a male preponderance (57 %). Fever (99 %), myalgia (52 %), headache (43 %), cough (14 %), conjunctival congestion (14 %), altered sensorium (13 %) and haemorrhagic manifestations (8%) were seen in the first phase. A total of 18 % of the patients came back with a second febrile episode. The features of meningoencephalitis were seen in 34 % of the patients during the second phase. Leucopenia, thrombocytopenia, and increase in liver enzymes, creatine phosphokinase (CPK) and activated partial thromboplastin time (APTT) was seen in the first phase but not in the second phase. Higher age, myocarditis, altered sensorium in the first phase, hypotension at admission, lower platelet count, elevated liver enzymes, higher APTT and CPK, were significantly associated with mortality. CONCLUSION: The primary care physicians or travel medicine practitioners should be aware of the distinct clinical and laboratory manifestations of KFD, including the ones that may signify requirements of higher levels of care.

In silico Study to Evaluate the Antiviral Activity of Novel Structures against 3C-like Protease of Novel Coronavirus (COVID-19) and SARS-CoV.

BACKGROUND: Globally, over 4.3 million laboratory confirmed cases of COVID-19 have been reported from over 105 countries. No FDA approved antiviral is available for the treatment of this infection. Zhavoronkov et al., with their generative chemistry pipeline, have generated structures that can be potential novel drug-like inhibitors for COVID-19, provided they are validated. 3C-like protease (3CLP) is a homodimeric cysteine protease that is present in coronaviruses. Interestingly, 3CLP is 96.1% structurally similar between SARS-CoV and SARS-CoV-2. OBJECTIVE: To evaluate interaction of generated structures with 3CLP of SARS-CoV (RCSB PDB ID: 4MDS). METHODS: Crystal structure of human SARS-CoV with a non-covalent inhibitor with resolution: 1.598 Å was obtained and molecular docking was performed to evaluate the interaction with generated structures. The MM-GBSA and IFD-SP were performed to narrow down to the structures with better binding energy and IFD score. The ADME analysis was performed on top 5 hits and further MD simulation was employed for top 2 hits. RESULTS: In XP docking, IFD-SP and molecular dynamic simulation studies, the top 2 hits 32 and 61 showed interaction with key amino acid residue GLU166. Structure 61, also showed interaction with HIS164. These interactions of generated structure 32 and 61, with GLU166 and HIS164, indicate the binding of the selected drug within the close proximity of 3CLP. In the MD simulation, the protein- ligand complex of 4MDS and structure 61 was found to be more stable for 10ns. CONCLUSION: These identified structures can be further assessed for their antiviral activity to combat SARS-CoV and COVID-19.