Interplay between Hepatitis E Virus and Host Cell Pattern Recognition Receptors.

Hepatitis E virus (HEV) usually causes self-limiting acute hepatitis, but the disease can become chronic in immunocompromised individuals. HEV infection in pregnant women is reported to cause up to 30% mortality, especially in the third trimester. Additionally, extrahepatic manifestations like neuronal and renal diseases and pancreatitis are also reported during the course of HEV infection. The mechanism of HEV pathogenesis remains poorly understood. Innate immunity is the first line of defense triggered within minutes to hours after the first pathogenic insult. Growing evidence based on reverse genetics systems, in vitro cell culture models, and representative studies in animal models including non-human primates, has implicated the role of the host's innate immune response during HEV infection. HEV persists in presence of interferons (IFNs) plausibly by evading cellular antiviral defense. This review summarizes our current understanding of recognizing HEV-associated molecular patterns by host cell Pattern Recognition Receptors (PRRs) in eliciting innate immune response during HEV infection as well as mechanisms of virus-mediated immune evasion.

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.

Typhoid spondylodiscitis mimicking tuberculosis in a teenage girl.

Salmonella Typhi cause a broad spectrum of human illnesses like gastroenteritis, typhoid fever, and bacteremia. It has also been recognized as a causative organism of osteomyelitis for more than a century but the incidence appears to be uncommon. Microbiological workup plays important role in the diagnosis of Typhoid spondylodiscitis as most of the time it mimics tuberculosis and misguide the clinician, especially in the developing world. Here, we reported an uncommon case of lumbar spondylodiscitis by Salmonella Typhi in an immunocompetent teenager, with the help of clinical, microbiological and radiological evidence. The case was managed conservatively after posterior spinal stabilization.

Unusual Severe Extra-Intestinal Manifestations of a Common Enteric Pathogen-Aeromonas Spp.

INTRODUCTION: Aeromonas spp. are halophilic, Gram-negative bacilli. They are widely distributed in the soil and aquatic environment and have been associated with various extra-intestinal infections, such as skin and soft-tissue infections, meningitis, bacteraemia etc. The most common species associated with extra-intestinal infection is Aeromonas hydrophila. AIM: To get the overview of clinical presentations, underlying predisposing factors associated with the extra-intestinal infections caused by Aeromonas species and their antimicrobial susceptibility pattern. MATERIALS AND METHODS: Extra-intestinal cases of Aeromonas spp. admitted during December 2015 to October 2016 in the tertiary care hospital of South Karnataka coastal region were analysed retrospectively. The isolates were identified by Matrix Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) VITEK®MS and antimicrobial susceptibility testing was performed by VITEK®2 system (bioMérieux, Inc., Durham, NC) respectively. Clinical manifestations and management of the cases were noted from the clinical records. Clinical and microbiological findings presented as mean±standard deviation, frequency and percentage. RESULTS: We included 26 cases in this study, from whom Aeromonas spp. were isolated alone or with another microorganism. Most widespread infection was Skin and Soft Tissue Infection (SSTI) (24, 92.3%). In 50% (12/24) cases, SSTI developed due to trauma. In 45.8% (11/24), underlying co-morbid conditions were present. The common site of infection was lower extremities (16/24, 66.7%) and 62.5% (15/24) of them presented with severe gangrene of the affected site. Other than SSTI, we encountered with two cases of keratitis and cholangitis respectively. A. hydrophila were frequently isolated species (23/26, 88.5%). The analysis of antimicrobial susceptibility showed, 13% isolates were Multidrug Resistant (MDR). Carbapenem resistance was also noted. CONCLUSION: We had isolated Aeromonas spp. from different extra-intestinal sites. Most common extra-intestinal manifestation by this organism was post-traumatic wound infection. Clinical spectrum of this infection confused the clinician with other organisms like group B Streptococcus, Clostridium spp. etc., and mislead them in empirical management. Finally with the microbiological support all the cases were treated either conservatively or in combination with surgical debridement or amputation depending on the situation.

Comparing Assay Performance of ELISA and Chemiluminescence Immunoassay in Detecting Antibodies to Hepatitis B Surface Antigen.

INTRODUCTION: Antibodies to Hepatitis B surface Antigen (Anti-HBs) levels are measured as markers for immune response to vaccination and in decision making for post-exposure prophylaxis against Hepatitis-B. Several immunoassay formats are used to measure Anti-HBs, thus carrying the possibility of variation in measured levels between different assays. This study compares the performance of Chemiluminescence Immunoassay (CLIA) against Enzyme-linked Immunosorbent Assay (ELISA) in measuring Anti-HBs titer by looking into concordance between the two test reports. AIM: To compare the agreement between ELISA and CLIA in measurement of Anti-HBs antibody titers. MATERIALS AND METHODS: This prospective comparative study conducted at Kasturba Medical College, Manipal measured consecutive serum samples (69) sent for anti-HBs levels during May-June 2016 using both CLIA (Abbott Architect) and ELISA (Bio-Rad). Anti-HBs values of ≤10mIU/ml was considered as non-protective and >10mIU/ml as protective. The agreement between the tests in classifying the antibody titers as non-protective or protective was computed using Kappa coefficient, and the difference in individual titer values between the tests compared using Bland-Altman plot on SPSS (v.15). RESULTS: Out of the 69 samples analysed, 18 samples (26.1%) were of health-care personnel and remaining of patients. Agreement between ELISA and CLIA in identifying the antibody titers as protective and non-protective were 96.5% and 90.9% respectively, resulting in an agreement of 0.84. The coefficient-of-variation of ELISA and CLIA were 74.5% and 113.1%, respectively. Three value based discordant results were noted; two samples deemed protective by ELISA were reported as non-protective by CLIA. One non-protective titer by ELISA was reported as protective by CLIA. CONCLUSION: Analytical agreement is good between the two immunoassays. However there are some discrepancies in quantitative measurement. This may have been due the variation in the standard calibrators used in each assay. Though CLIA showed more variation in the values, it has the advantage of being automated test with low turn around time. Therefore, both the test methodologies can be reliably used in place of each other for detection of Anti- HBs titer.