Scrub Typhus Research Articles

Global and regional seroprevalence, incidence, mortality of, and risk factors for scrub typhus: A systematic review and meta-analysis

ObjectivesScrub typhus is underdiagnosed and underreported but emerging as a global public health problem. We aimed to provide the first comprehensive review on the seroprevalence, incidence, mortality of and risk factors for scrub typhus. MethodsWe searched PubMed, Scopus, Web of Science, China National Knowledge Infrastructure and other databases. Trended incidence and median mortality were calculated and pooled seroprevalence and risk factors for scrub typhus were evaluated using the random-effects meta-analysis. ResultsWe included 663 articles from 29 countries/regions. The pooled seroprevalence was 10.73% (95%CI 9.47-12.13%) among healthy individuals and 22.58% (95%CI: 20.55%-24.76%) among febrile patients. Mainland China reported the highest number of cases and South Korea and Thailand had the highest incidence rates. Median mortalities were 5.00% (range: 0.00-56.00%) among hospital inpatients, 6.70% (range: 0.00-33.33%) among patients without specified admission status and 2.17% (range: 0.00-22.22%) among outpatients. The significant risk factors included agricultural work, specific vegetation exposure, other outdoor activities, risky personal health habits, and proximity to rodents, livestock, or poultry. ConclusionsOur comprehensive review elucidates the significant yet variable burden of scrub typhus across different regions, underscoring its emergence as a critical public health concern globally.

Seroprevalence and Clinical Profile of Leptospirosis and Scrub Typhus in Clinically Suspected Patients at a Tertiary Care Center: A Retrospective Study from Theni, Tamil Nadu

Abstract Background: Leptospirosis and Scrub typhus are zoonotic illnesses that are found worldwide. Scrub typhus is a rickettsial infection caused by Orientia tsutsugamushi and spread through the biting of a mite’s chigger. Leptospirosis is an anthropozoonotic illness that can be found anywhere but is most common in tropical and subtropical areas. In this study, we report the seroprevalence of Scrub typhus and Leptospirosis with relation to demographic factors in clinically suspected patients attending a tertiary care hospital in Theni, Tamil Nadu. Methods: This is a retrospective study in which 9574 serum samples from clinically suspected cases were collected from January 2018 to December 2023 and tested for immunoglobulin M (IgM) antibodies for Scrub typhus using the enzyme-linked immunosorbent assay (ELISA) and rapid test. A blood sample was taken from each patient, and an IgM ELISA was performed to make the diagnosis. The ELISA cut-off was determined. Results: In this study, 9574 probable cases, 4306 were examined for Leptospira IgM ELISA and 5268 for Scrub typhus IgM ELISA. Out of 4306 suspected Leptospira cases, 167 (3.8%) were positive and 485 (9.2%) were positive in 5268 suspected Scrub typhus cases. The bulk of Leptospirosis and Scrub typhus cases were in the 21–40 years’ age range, followed by the 0–20 years’ age range. Males were found to have higher seroprevalence (57.1%) than females (42.9%). Conclusions: Scrub typhus and leptospirosis are developing infections, and prompt treatment can save many lives. It is strongly advised to take a programmatic approach to the prevention, control, and management of these developing diseases.

Advanced serological tests – A paradigm shift in the diagnosis of febrile illnesses even with some atypical manifestations

Background: Fever is a symptom, not a disease. It is the non-specific manifestation of several underlying illnesses. Aims and Objectives: The aims and objectives of this study were to determine the serological profile of patients with febrile illnesses, to study their different unusual presentations, and to study patients with coinfections with more than one type of disease. Materials and Methods: Blood samples from 15,000 febrile patients were collected during the study period of 6 months. Different serological tests were performed in our laboratory based on clinical suspicion and in a few patients, more than one type of tests were done. The unusual presentations of different diseases were studied. Results: Various percentages of male and female patients were seen suffering from different types of febrile illnesses. The different positive results out of total tests done for respective diseases were dengue (848/7708), vivax malaria (64/800), falciparum malaria (4/800), leptospirosis (95/798), scrub typhus (77/2433), enteric fever (75/1506), hepatitis B (143/9368), hepatitis C (11/9368), human immunodeficiency virus (HIV) (37/10900), systemic lupus erythematosus (5/158), acute renal failure (66/158), and syphilis (54/583). Different unusual presentations among patients with several diseases were noted, along with their percentages of occurrence. Coinfections among dengue and enteric fever (3%), mixed infection with Plasmodium vivax and Plasmodium falciparum (0.25%), scrub typhus and Leptospira (15.6%), hepatitis B and hepatitis C (0.649%), hepatitis B and HIV (5%), hepatitis C and HIV (8.33%), and syphilis and HIV (27.68%). Conclusion: Dengue fever was found to be the most common of all febrile illnesses. The different unusual presentations of those diseases should suggest an improved clinical suspicion and better diagnostic stewardship. Coinfection was most commonly seen among syphilis and HIV and these data must suggest to always looking for associated illnesses in a patient with a single diagnosis.

Correlation between genotypes of Orientia tsutsugamushi and clinical characteristics of patients with scrub typhus in Guangzhou, China

Objective: To explore the correlation between genotypes of Orientia (O.) tsutsugamushi and clinical characteristics of scrub typhus patients. Methods: Clinical data of patients with scrub typhus admitted to different types of medical institutions in Guangzhou from September 2012 to December 2016 were collected using medical records. Demographic data, clinical manifestations, as well as hematological and biochemical indicators of patients infected with different genotypes were analyzed and compared. Results: A total of 192 patients were included in this study, including 121 patients with Karp genotype of O. tsutsugamushi infection (63.0%), 36 patients with Gilliam genotype (19.0%), 23 patients with Kato genotype (12.0%), and 12 patients with TA763 genotype (6.0%) infection. The median value of albumin in patients with Karp genotype infection was significantly lower than that of Gilliam-infected patients (P=0.032). Patients with Karp genotype infection had a significantly longer hospital stay (9 days) than those with Gilliam genotype (7 days) (P=0.009) and Kato genotype infection (6 days) (P=0.005). Karp-infected patients also represented for the largest number of patients with complicated organ involvement (88/133, 66.2%). Furthermore, Karp-infected patients had higher risk of developing multiple organ dysfunction syndrome (18.2%) and requiring intensive care unit treatment (15.9%). Besides, patients with Gilliam genotype (8 days) and TA763 genotype infection (7.5 days) had shorter fever duration than those with Karp genotype (9 days) and Kato genotype (9 days) infection, respectively. Conclusions: Genotypes of Orientia tsutsugamushi were associated with varying clinical manifestations, organ involvement, and treatment outcomes, suggesting that genotypes ranged in virulence.

A Comparative Study of Community-acquired Acute Kidney Injury and Hospital-acquired Acute Kidney Injury from a Tertiary Care Hospital in North India.

In this observational study, clinical characteristics, etiologies, and outcomes of patients admitted to the hospital with community-acquired acute kidney injury (CAAKI) have been compared in contrast to those who hospital-acquired Acute Kidney Injury (HAAKI). This was a prospective study of adults aged 18 years or above diagnosed with acute kidney injury (AKI) over a period of 17 months at a tertiary care hospital. 230 patients had AKI with the mean age of the study population being 45.33 ± 12.68 years. 178 (77.4%) patients were enrolled from medical unit, 25 (10.7%) from surgical unit, and 27 (11.7%) from obstetrical unit. The observed incidence of AKI was 15/1000 admissions. About 58.2% had CAAKI and 96 (43.7%) had HAAKI. Out of 230 patients, 170 (73.9%) patients were male and 60 (26.1%) were female. Sepsis was the most common (52.1%) etiology of AKI among the medical cases. Urosepsis, scrub typhus, and pneumonia were the most common causes of AKI. Sixty percent of AKI was Kidney Disease Improving Global Outcomes Stage 1 or 2 and 40% was in Stage 3. Oliguria was seen in 56.5%, hyperkalemia in 34.7%, fluid overload in 6.1%, and metabolic acidosis in 22.6%. The majority of patients had multiple organ involvement (52.1%) at the time of enrollment. About 116 (50.4%) had lung injury requiring mechanical ventilation and 95 (41.3%) were on inotropes. Mortality occurred in 19.5%. Anemia, the use of vasopressor drugs, and the need for intensive care support were independent predictive factors for mortality. AKI was common in hospitalized patients and leads to significant inhospital mortality. AKI is largely a CAAKI, and the lesser extent is due to HAAKI. Many causes are potentially preventable. Early fluid resuscitation, effective antibiotics, appropriate antidotes, and timely referral of established AKI patients to centers with dialysis facilities can improve AKI outcomes.

Flea-Borne Rickettsioses and Scrub Typhus in Patients with Suspected Arbovirus Infection in Bangkok, Thailand.

Background: In urban Thailand, arboviral infections dominate diagnoses of acute undifferentiated fevers (AUFs) owing to their well-defined epidemiology and characteristic clinical presentations. However, rickettsial diseases, also endemic in this setting, remain under-recognized owing to challenges in early detection. Objective: This study aimed to identify potential rickettsial infections among patients with AUF in Bangkok and vicinity utilizing leftover nucleic acid extracted from serum samples from patients initially suspected of but negative for arbovirus infections. Materials and Methods: A total of 609 nucleic acid samples were screened for rickettsial bacteria using real-time PCR, targeting the 17-kDa common antigen gene of Rickettsia spp. and the 47-kDa gene of Orientia tsutsugamushi. Results: Nine samples were positive for Rickettsia spp. and two were positive for O. tsutsugamushi. DNA sequence and phylogenetic analyses based on partial 17-kDa antigen and citrate synthase (gltA) genes identified the Rickettsia-positive samples as R. typhi in eight cases and R. felis in one case. Analysis of the 56-kDa type-specific antigen gene identified the two O. tsutsugamushi isolates as Gilliam-related genotypes. Although rickettsial diseases typically present with mild symptoms, two patients with R. typhi infection (murine typhus) developed respiratory distress syndrome, highlighting the potential for rare but serious complications. Conclusion: This study underscores the critical importance of differential diagnosis and prompt, effective intervention to prevent complications in suspected cases.

Recognizing The Significance of Scrub Typhus as An Emerging Threat

Recognizing The Significance of Scrub Typhus as An Emerging Threat

Incidence of Scrub Typhus according to Changes in Geographic and Demographic Characteristic in the Chungcheong Region of Korea.

To ascertain the incidence trends of scrub typhus in the Chungcheong region, we analyzed the epidemiological survey information of 14,379 cases of scrub typhus reported to the integrated disease health management system of the Korea Centers for Disease Control and Prevention between 2012 and 2022, along with demographic data from the Korean Statistics Information Service. Geographical analyses were performed to confirm the correlation between high-risk areas and the proportion of elderly people. The average age, proportion of elderly people, and changes in the agricultural population were statistically associated with incidence. The incidence of scrub typhus, and the agricultural population, in the Chungcheong region has decreased compared with that in 2012-2013. However, recent trends indicate a resurgence linked to increased outdoor activity, with higher risks observed in older age groups. Additionally, advancing age correlates with a heightened probability of reinfection and additional infections with other febrile diseases. The incidence of scrub typhus in the Chungcheong region (2012-2022) is changing according to age and route of infection, highlighting the need for revised prevention and promotion policies.

Re-Emergence of Scrub Typhus as a Public Health Problem in India: Its Spatial and Temporal Distribution Based on Analysis of 15-Year Data of the National Integrated Disease Surveillance Programme

Re-Emergence of Scrub Typhus as a Public Health Problem in India: Its Spatial and Temporal Distribution Based on Analysis of 15-Year Data of the National Integrated Disease Surveillance Programme

Reconstitution of human microglia and resident T cells in the brain of humanized DRAGA mice.

Humanized mouse models are valuable tools for investigating the human immune system in response to infection and injury. We have previously described the human immune system (HIS)-DRAGA mice (HLA-A2.HLA-DR4.Rag1KO.IL-2RgKO.NOD) generated by infusion of Human Leukocyte Antigen (HLA)-matched, human hematopoietic stem cells from umbilical cord blood. By reconstituting human cells, the HIS-DRAGA mouse model has been utilized as a "surrogate in vivo human model" for infectious diseases such as Human Immunodeficiency Virus (HIV), Influenza, Coronavirus Disease 2019 (COVID-19), scrub typhus, and malaria. This humanized mouse model bypasses ethical concerns about the use of fetal tissues for the humanization of laboratory animals. Here in, we demonstrate the presence of human microglia and T cells in the brain of HIS-DRAGA mice. Microglia are brain-resident macrophages that play pivotal roles against pathogens and cerebral damage, whereas the brain-resident T cells provide surveillance and defense against infections. Our findings suggest that the HIS-DRAGA mouse model offers unique advantages for studying the functions of human microglia and T cells in the brain during infections, degenerative disorders, tumors, and trauma, as well as for testing therapeutics in these pathological conditions.

A case of scrub typhus with meningitis as the onset: Case report and literature review.

Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon. A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation. The patient was diagnosed with a central nervous system infection. Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders. Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided. The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective. Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.

Orientia tsutsugamushi: An Unusual Intracellular Bacteria-Adaptation Strategies, Available Antibiotics, and Alternatives for Treatment.

During evolution Orientia tsutsugamushi became a smarter obligate bacterium to establish as intracellular pathogens. O. tsutsugamushi is a human pathogenic bacterium responsible for 1 billion infections of scrub typhus. Several novel mechanisms make this bacterium unique (cell wall, genetic constitutions, secretion system, etc.). In 2007, O. tsutsugamushi Boryong was pioneer strain for whole-genome sequencing. But the fundamental biology of this bacterial cell is a mystery till date. The unusual biology makes this organism as model for host cell interaction. Only a few antibiotics are effective against this intracellular pathogen but emergence of less susceptibility toward antibiotics make the situation alarming. The review was captivated to highlight the unusual aspects of adaptation, antibiotics, and drugs beyond antibiotics.

A Case Series on Spotted Fever and Typhus Fever Seropositivity at National Center for Disease Control and Epidemiological Perspective.

Background: The rickettsioses, except for typhus fever and scrub typhus (ST), were not really recognized as distinct clinical entities until the early 20th century. Only when specific rickettsial serologic testing was introduced in the 1940s could the precise etiologies of various rickettsial diseases (RDs) be determined with certainty. Although ST is a well- recognized zoonotic disease entity, but non-scrub typhus rickettsial infection like spotted fever group and typhus group are not well studied in India and are still underestimated. Methods: We report cases who had shown seropositivity of spotted fever and typhus fever RD in IgM and IgG ELISA whose samples were referred from various hospitals of Delhi/National Capital Region in which clinicians had strong suspicion of rickettsiosis other than ST or Weil-Felix test found positive for any of the OX2, 19, and K antigens. Results: We reported 18 cases of SFG and TGRD with mostly cases presented with fever followed by hepato-intestinal symptoms. Conclusion: The vast variability and nonspecific presentation of rickettsiosis in spotted and typhus fever at times have often made it difficult to diagnose clinically. Prompt antibiotic therapy shortens the course of the disease, lowers the risk of complications, and in turn, reduces morbidity and mortality owing to RDs. There is a distinct need for physicians and health care workers at all levels of care in India to be aware of the clinical features, available diagnostic tests and their interpretation, and the therapy for these infections.

Utility of next-generation sequencing for the etiological diagnosis of Orientia tsutsugamushi infection

BackgroundScrub typhus, an acute febrile disease caused by Orientia tsutsugamushi, is transmitted to humans through infected chigger mites. We present a case of scrub typhus in a previously healthy man from Shandong Province diagnosed using next-generation sequencing (NGS) and PCR and review recent literature on NGS for scrub typhus diagnosis. MethodsNGS was utilized for testing whole blood collected on admission. Confirmatory testing was done by detecting IgM and IgG antibodies to Orientia in acute and convalescent sera by ELISA. Orientia 47-kDa protein gene TaqMan and standard PCR of the 56-kDa protein gene and Sanger sequencing were performed on eschar scab DNA. ResultsThe NGS diagnosis was confirmed by 47-kDa protein gene TaqMan and sequencing of a fragment of the O. tsutsugamushi 56-kDa protein gene from the eschar scab. Analysis of this sequence and the NGS data indicated O. tsutsugamushi strain Cheeloo2020 is a novel genotype. Mapping of the NGS data against the O. tsutsugamushi Gilliam strain genome sequence identified 304 reads with high similarity. ConclusionsNGS is not only useful for multiplex diagnosis of scrub typhus, but also provides insight into the genetic diversity of O. tsutsugamushi. The common failure to submit sequences to databases makes it difficult to determine the minimal quantity and quality of NGS data being used for the positive identification of Orientia DNA in clinical specimens.

CLINICAL AND LABORATORY PROFILE OF ADMITTED PATIENTS PRESENTING WITH FEBRILE ILLNESS DUE TO DENGUE AND SCRUB TYPHUS COINFECTION FROM A TERTIARY CARE HOSPITAL IN SOUTH RAJASTHAN, INDIA

Objective: The present study aims at describing the clinical features, laboratory diagnosis, and complications in patients presenting with febrile illness due to scrub typhus and dengue coinfection from Southern Rajasthan, India. Method: This present prospective, observational, and hospital-based study conducted in the Department of Microbiology of AIMS & RC, Rajsamand, located in Southern Rajasthan, from January 2021 to December 2021. Scrub typhus was diagnosed in the microbiology laboratory by performing SD Bioline, one-step scrub typhus for the detection of IgM antibody, and dengue fever using J.mitra and Co. Pvt. Ltd., rapid card test for the detection of NS1 antigen and IgM antibody. Result: Out of 500 patients suspected of AUFI, 25 (5%) patients diagnosed of having dengue and scrub typhus coinfection. Fever was present in all 25 (100%) patients and 13 (52%) of patients had arthralgia, nausea, and vomiting. The most common sign noticed in our study was pallor and icterus in 10 (40%) patients each followed by shock/hypotension in 8 (32%) and hepatosplenomegaly in 5 (20%). The most predominant laboratory finding was thrombocytopenia (<1.0 × 106/cumm) in 23 (92%) patients, while elevated bilirubin (>2 mg/dl) in 22 (88%) and elevated transaminase and prolonged aPTT in 21 (84%) patients each. The majority of patients 23 (92%) had hepatic dysfunction, i.e., in followed by multi-organ dysfunction (MODS) in 15 (60%). Conclusion: In developing countries like India, particularly in tropical areas, dengue, and scrub typhus coinfection is under-recognized entity. Additional investigation should be carried out in cases of AUFI patients with features such as hypotension, leukocytosis, early drop in platelet counts, and hypoalbuminemia.

Aetiological profile of acute encephalitis syndrome in Assam, India, during a 4-year period from 2019 to 2022.

Acute encephalitis syndrome (AES) is a major public health concern in India as the aetiology remains unknown in the majority of cases with the current testing algorithm. We aimed to study the incidence of Japanese encephalitis (JE) and determine the aetiology of non-JE AES cases to develop an evidence-based testing algorithm. Cerebrospinal fluid (CSF) samples were tested for Japanese encephalitis virus by ELISA and polymerase chain reaction (PCR). Multiplex real-time PCR was done for Dengue, Chikungunya, West Nile, Zika, Enterovirus, Epstein Barr Virus, Herpes Simplex Virus, Adenovirus, Cytomegalovirus, Herpesvirus 6, Parechovirus, Parvovirus B19, Varicella Zoster Virus, Scrub typhus, Rickettsia species, Leptospira, Salmonella species, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Plasmodium species and by ELISA for Mumps and Measles virus. Of the 3173 CSF samples, 461 (14.5%) were positive for JE. Of the 334 non-JE AES cases, 66.2% viz. Scrub typhus (25.7%), Mumps (19.5%), Measles (4.2%), Parvovirus B19 (3.9%) Plasmodium (2.7%), HSV 1 and 2 (2.4%), EBV and Streptococcus pneumoniae (2.1% each), Salmonella and HHV 6 (1.2% each) were predominant. Hence, an improved surveillance system and our suggested expanded testing algorithm can improve the diagnosis of potentially treatable infectious agents of AES in India.

Unravelling the Enigma of Scrub Typhus: A Critical Review and Insights Into Epidemiology, Clinical Features, Diagnostic Advances, and Emerging Trends.

Scrub typhus (ST) is caused by the bacterium Orientia tsutsugamushi, which exhibits significant antigenic diversity and is prevalent in the Asia-Pacific region. Its clinical presentation is characterized by non-specific symptoms such as headache, myalgia, sweating, and vomiting, along with the abrupt onset of fever and chills. An eschar is often visible in the axilla, groin, or inguinal area and is present in around half of the confirmed cases. The Weil-Felix test is the earliest detection technique, though it is not highly specific. Diagnostic procedures include biopsy, culture, serology, and PCR. The molecularly detectable amount of Orientiaein the bloodstreamoccasionally reaches levels that are identified during acute illness and vanish after the first round of appropriate antibiotic treatment. This study offers a thorough review of ST, a disease carried by vectors caused by Orientia tsutsugamushi.We emphasize on the significance of monitoring and awareness campaigns, diagnostic problems, and geographical differences. It is essential to use multidisciplinary techniques combining epidemiologists, public health authorities, and doctors. Sustained observation and research are essential for developing successful preventative and control measures. When participating in outdoor activities in areas known for such infections or at particular times of the year when ticks or mites carrythe rickettsia infection, people should take great precautions to prevent getting bitten by ticks or mites. Prompt medical evaluation is advised if suspicious symptoms or signs appear, especially in elderly individuals.

Etiological spectrum and diagnostic challenges of short-duration fever in West Bengal (India). A cross-sectional tertiary care study

IntroductionThe scarcity of epidemiological data on acute febrile illnesses from South Asia impairs evidence-based clinical decision-making. Our study aimed to explore the etiological spectrum of short-duration fever in patients admitted to a tertiary care hospital in West Bengal, India. MethodsWe conducted a cross-sectional study from May 2021 to April 2022 involving 150 adult patients presenting with a fever lasting less than two weeks at Burdwan Medical College and Hospital (West Bengal, India). We performed comprehensive clinical assessments, including microbiological, serological, and other specific investigations, to identify the causes of the fever. ResultsThe demographic profile predominantly included individuals aged 21–40 years, with a male-to-female ratio of 1.9:1; 60.7% of participants were from rural areas. The primary etiological agents identified were scrub typhus (25.3%), dengue (15.3%), and enteric fever (13.3%). Notably, 80% of patients presented with non-localizing symptoms, while 14.7% had respiratory symptoms. Blood cultures pinpointed Salmonella typhi and Staphylococcus aureus in a minority of cases (3.3%); malaria, primarily Plasmodium vivax, was diagnosed in 12% of the cases. ConclusionOur findings highlight the complexity of diagnosing short-duration fevers, dominated by a wide range of etiological agents, with a notable prevalence of scrub typhus. These results underscore the urgent need for enhanced diagnostic facilities, including the availability of scrub typhus testing at primary healthcare centers. We recommend empirical doxycycline therapy for suspected cases and emphasize the need for further research to develop management guidelines for acute febrile illnesses. This study also highlights the importance of raising both community and clinician awareness to prevent irrational antibiotic use.

Novel Drug Repurposing Strategy as an Alternative Therapeutic Concept for Scrub Typhus Using Computational Studies

Scrub typhus is one of the most underdiagnosed and unreported febrile illnesses caused by an obligate intracellular bacterium named Orientia tsutsugamushi and the antibiotics were the commonly prescribed drugs to treat the condition. Due to the widespread development of antimicrobial resistance to the standard drugs, the new therapeutic approach is warranted. The drug repurposing approach plays a novel concept in identifying alternative therapies to fight against pathogens. To investigate the anti-scrub typhus activity of nine newly FDA-approved antibiotics from 2018-2019 against Orientia tsutsugamushi deubiquitylase (OtDUB) compared with standard drugs. The structure of ligands was retrieved from the PubChem database and the crystal structure of target OtDUB (PDB ID: 6UPU) with a resolution of 2.2 Ao was retrieved from the Protein data bank. Molecular docking studies were performed using PyRx version 0.8 and the amino acid interactions were visualized using BIOVIA Discovery studio and the pharmacokinetic properties of the drugs were analysed by SWISS ADME software. The binding affinity of the drugs to deubiquitylase and amino acids was determined using the In silico approach, the drug Omadacycline shows superior activity when compared with other drugs. Based on our preliminary in-silico docking studies, we conclude that Omadacycline may be repurposed for the treatment of scrub typhus as it shows a higher binding affinity of -8.6 kcal/mol when compared to the standard drugs. For the further advancement of the study, in vitro and in vivo studies should be performed.

Thrombocytopenia in children with acute encephalitis syndrome: a prospective observational study

Background: The objective of this study is to find out the proportion of children with thrombocytopenia in acute encephalitis syndrome (AES); second, to compare the aetiology of AES in thrombocytopenic cases with non-thrombocytopenic cases; and finally, to find out clinical and laboratory predictors of thrombocytopenia in AES, as well as to study platelet aggregation and compare it in both scrub positive and scrub negative AES cases. Methods: This prospective observational study was conducted on 176 children with presumed viral aetiology were investigated to find out the cause of AES. Results: The majority of patients presented with thrombocytopenia. The most common aetiologies are Japanese encephalitis (JE). No significant difference was observed in the aetiology of AES between the thrombocytopenic and non-thrombocytopenic groups. Rash, bleeding, swelling, hepatomegaly, and splenomegaly were significantly more common in thrombocytopenic AES cases. Among the laboratory parameters, haemoglobin, PCV, and serum protein were found to be significantly low in the thrombocytopenic group. Liver enzymes, serum AST, and serum ALT were significantly high in the thrombocytopenic group. Platelet aggregation percentage was found to be significantly high in AES children who were positive for scrub typhus in comparison to other AES cases. Eighty-seven patients were discharged from the hospital. The mortality rate was 18%. There was no significant difference in the outcome of AES cases in relation to thrombocytopenia. Conclusions: This approach may help clinicians in the diagnosis of AES due to the scrub along with other tests available. There was no significant difference in the short-term outcome of AES cases in relation to thrombocytopenia.