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Scrub typhus, a vector-borne bacterial infection, is an important but neglected disease globally. Accurately characterizing the burden is challenging because of nonspecific symptoms and limited diagnostics. Prior seroepidemiology studies have struggled to find consensus cutoffs that permit comparisons of estimates across contexts and time. In this study, we present a novel approach that does not require a cutoff and instead uses information about antibody kinetics after infection to estimate seroincidence. We use data from three cohorts of scrub typhus patients in Chiang Rai, Thailand, and Vellore, India, to characterize antibody kinetics after infection and two population serosurveys in the Kathmandu Valley, Nepal, and Tamil Nadu, India, to estimate seroincidence. The samples were tested for IgM and IgG responses to Orientia tsutsugamushi-derived recombinant 56-kDa antigen using commercial enzyme-linked immunosorbent assay kits. We used Bayesian hierarchical models to characterize antibody responses after scrub typhus infection and used the joint distributions of the peak antibody titers and decay rates to estimate population-level incidence rates in the cross-sectional serosurveys. Median responses persisted above an optical density (OD) of 1.8 for 23.6 months for IgG and an OD of 1 for 4.5 months for IgM. Among 18- to 29-year-olds, the seroincidence was 10 per 1,000 person-years (95% CI, 5-19) in Tamil Nadu, India, and 14 per 1,000 person-years (95% CI: 10-20) in the Kathmandu Valley, Nepal. When seroincidence was calculated with antibody decay ignored, the disease burden was underestimated by more than 50%. The approach can be deployed prospectively, coupled with existing serosurveys, or leverage banked samples to efficiently generate scrub typhus seroincidence estimates.

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. [ABSTRACT FROM AUTHOR]

Scrub typhus meningoencephalitis (STME) is an uncommon but fatal complication of scrub typhus that requires extra diligence in early identification and treatment. The goal of this study was to look at the clinical characteristics, laboratory results, and outcome of STME in children. A retrospective study was conducted in the paediatric intensive care unit of a tertiary care hospital in Eastern India between April 2021 and September 2022. It was carried out in children aged 1 month–12 years. Sixteen children were diagnosed with STME out of 75 acute encephalitis syndrome (AES) cases. The male-to-female ratio was 3:1, with a mean age of 4.28 ± 3.36 years. All the children hailed from rural areas. Fever (100%), convulsions (87.5), altered sensorium (93.75%), nuchal stiffness (25%), vomiting (75%), pallor (75%), and hepatomegaly (50%) were the most prevalent clinical manifestations. The average duration of fever upon presentation was 8.25 ± 2.11 days and the average length of hospital stay was 9.00 ± 4.59 days. The complications encountered were shock (3), interstitial pneumonia (1), myocarditis (1), raised intracranial pressure (1), and right-sided hemiplegia (1). Fifteen children recovered completely, whereas one child suffered from residual right-sided neurodeficit. A high index of suspicion needs to be maintained for STME as a possible AES entity, as anti-scrub measures administered promptly can go a long way in mitigating the related morbidity and mortality especially in resource-constrained settings. [ABSTRACT FROM AUTHOR]

Background Scrub typhus is highly endemic in northern Thailand yet awareness and knowledge are low. We developed a community engagement project to improve awareness in communities at risk of contracting scrub typhus. Methods We conducted a series of engagement sessions with healthcare workers and community health volunteers so they would, in turn, engage with their communities. We evaluated our activities by assessing the increase in scrub typhus knowledge, using a series of Likert-scale items and open-ended questions. Three to 6 months after the sessions, participants were followed up to collect their experiences training community members. Results Of 134 participants who took part in eight sessions, 87.3% were community health volunteers. Disease knowledge increased substantially after the sessions and was well maintained for up to 5 mo. Satisfaction was high and, through participant feedback, engagement materials were improved to be more useful to the communities. People with higher education had higher scores and retention. Conclusions Community engagement was shown to be an effective tool to develop and carry out health-promoting activities in a culturally and context-appropriate manner. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus (ST, also known as tsutsugamushi disease) is a common febrile vector-borne disease in South Korea and commonly known as autumn- and female-dominant disease. Although understanding changes in seasonality and sex differences in ST is essential for preparing health interventions, previous studies have not dealt with variations in periodicity and demographic characteristics in detail. Therefore, we aimed to quantify the temporal dynamics of seasonal patterns and sex differences in the incidence of ST in South Korea. Methods: We extracted epidemiological week (epi-week)-based ST cases from 2003 to 2019 Korean National Health Insurance Service data (ICD-10-CM code: A75.3). To determine changes in seasonality and sex differences, year-, sex-, and age-group-stratified male-to-female ratios and wavelet transform analyses were conducted. Results: Between 2003 and 2019, 213,976 ST cases were identified. The incidence per 100,000 population increased by 408.8% from 9.1 in 2003 to 37.2 in 2012, and subsequently decreased by 59.7% from 2012 to 15.0 in 2019. According to the continuous wavelet transform results, ST exhibited a dual seasonal pattern with dominant seasonality in autumn and smaller seasonality in spring from 2005 to 2019. Overall, the periodicity of seasonality decreased, whereas its strength decreased in autumn and increased in spring. With an overall male-to-female ratio being 0.68:1, the ratio has increased from 0.67:1 in 2003 to 0.78:1 in 2019 (Kendall's τ = 0.706, p < 0.001). However, interestingly, the ratio varied significantly across different age groups. Conclusions: Our findings quantitatively demonstrated changes in seasonality with dual seasonal pattern and shortened overall periodicity and a decrease in sex differences of ST in South Korea. Our study suggests the need for continuous surveillance on populations of vector and host to address ST dynamics to preemptively prepare against global warming. [ABSTRACT FROM AUTHOR]

Scrub typhus is an acute illness caused by the bacteria Orientia tsutsugamushi and is transmitted by mites. Scrub typhus propagates via infected chigger bites (larval stage). Diagnosing scrub typhus is challenging due to its ability to mimic symptoms of other febrile illnesses. Conventional methods such as Weil‐Felix, ELISA, and PCR are available for diagnosing scrub typhus. The Weil‐Felix test was formerly used in developing nations to diagnose scrub typhus, but it is not recommended since it lacks both specificity and sensitivity. IFA and ELISA are superior for detecting scrub typhus; however, they are not as effective at detecting the illness in its early stages and require convalescent sampling to confirm positive samples. However, because the Orientia tsutsugamushi serotypes differ in their genetic makeup, PCR‐based approaches have become less applicable despite their higher specificity and sensitivity. Nanomaterial‐based biosensing could help detect scrub typhus early due to its high surface area, electrical conductance, and chemical stability. This study emphasizes the need for point‐of‐care detection of this under‐diagnosed but fatal disease, emphasizing the importance of nanobiosensors in early diagnosis. The pathophysiology of scrub typhus, standard diagnostic procedures, and the critical role that nanobiosensors play in the early detection of scrub typhus are discussed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Background Globally, India has a high zoonotic disease burden and lacks surveillance data in humans and animals. Rodents are known reservoirs for many zoonotic diseases and their synanthropic behavior poses a great public health threat. Methods In this study, trapped rodents/shrews from randomly selected villages within Puducherry, India, and their ectoparasites were screened for zoonotic pathogens, namely, Orientia tsutsugamushi , other pathogenic rickettsiae, Leptospira spp. Cryptosporidium spp. Coxiella burnetii and methicillin-resistant Staphylococcus aureus (MRSA) using conventional PCR. A total of 58 rodents/shrews were trapped from 11 villages. The species trapped were Suncus murinus (49/58, 84.48%), Rattus rattus (8/58, 13.79%) and Rattus norvegicus (1/58, 1.72%). All ectoparasites collected were identified as mites and its infestation rate was 46.55% (27/58). Results Real-time PCR targeting the 47 kDa gene of O. tsutsugamushi revealed positivity in one rodent and one shrew (3.45%) and two mite pools (7.41%). Conventional PCR targeting the 56 kDa gene revealed positivity in one shrew and two mite pools and the phylogenetic analysis of all three amplicons indicated the circulation of the Gilliam-related serotype. MRSA was detected in the alimentary tract of a shrew (1/32, 3.13%). Leptospira spp. Rickettsia, Cryptosporidium spp. and Co. burnetii tested negative. Conclusions The detection of zoonotic pathogens within reservoir hosts and vectors poses a risk of transmission to humans. This study signifies the need for zoonotic pathogen surveillance in synanthropic rodents/shrews. [ABSTRACT FROM AUTHOR]

Prior to the devastating earthquake in Nepal in 2015, scrub typhus was not recognized as a highly endemic disease in the country. This contrasted with neighboring India, where scrub typhus is endemic and there have been sporadic outbreaks of severe forms. This discrepancy underscores the limitations in our comprehensive understanding of the scrub typhus epidemiological patterns in Nepal, especially before 2015. To better understand the dynamic and current status of scrub typhus, this study investigated its prevalence among patients with acute febrile illness in two hospitals located in Pokhara city, Kaski district and Bharatpur city, Chitwan district during 2009–2010. Our findings revealed that 31.5% (239 of 759 patients) of the cases were positives for scrub typhus based on serological and pathogen detection assays. These results provide crucial insights into the pre-earthquake endemicity of scrub typhus in Nepal, implying its long-standing presence in the region prior to the significant environmental transformations caused by the 2015 earthquake. This study also emphasizes the need for heightened awareness and improved diagnostic capabilities to effectively manage and control scrub typhus, which remains a significant public health concern in Nepal. [ABSTRACT FROM AUTHOR]

Objectives: Scrub typhus is the most common rickettsial disease in India, caused by Orientia tsutsugamushi and transmitted by chigger mites. Previously prevalent in South India, a resurgence of scrub typhus cases has recently affected Eastern India. This study aimed to estimate the prevalence and describe the clinicolaboratory profile of scrub typhus in paediatric patients (1-12 years old) living in Eastern India. Methods: This prospective observational study was conducted from January to December 2019 at the Dr B C Roy Post Graduate Institute of Paediatric Sciences, Kolkata, India. All acute undifferentiated cases of febrile illness, in patients aged between 1-12 years, were tested using scrub typhus serology by ELISA. Demographic details, clinical features, laboratory findings, complications and treatment outcomes of these scrub typhus patients were extracted and analysed. Results: Out of 1,473 patients with acute febrile illness, 67 (4.5%) children were diagnosed with scrub typhus. The mean age of the selected patients was 5.22 ± 3.05 years, and the majority (64.2%) had been running a fever since the preceding 7-14 days. Gastrointestinal symptoms such as vomiting (43.3%) and abdominal pain (32.8%) were most frequently observed. Major clinical signs of scrub typhus were hepatomegaly (41.8%) and splenomegaly (31.3%). Complications were observed in 74.6% of patients, with thrombocytopenia (40.3%) and meningoencephalitis (29.9%) occurring more frequently. The case fatality rate of the study sample was 1.5%. Conclusion: Classical eschar was absent in three-fourth of the studied patients. Hence, this study advocates laboratory scrub typhus tests for all suspected cases in the endemic region (Eastern India). Prompt treatment with doxycycline and/or azithromycin could prevent complications such as thrombocytopenia/meningoencephalitis and reduce mortality. [ABSTRACT FROM AUTHOR]

Purpose: The mechanisms that control inflammation in scrub typhus are not fully elucidated. The Notch pathways are important regulators of inflammation and infection, but have not been investigated in scrub typhus. Methods: Plasma levels of the canonical Notch ligand Delta-like protein 1 (DLL1) were measured by enzyme immunoassay and RNA expression of the Notch receptors (NOTCH1, NOTCH2 and NOTCH4) in whole blood was analyzed by real-time PCR in patients with scrub typhus (n = 129), in patients with similar febrile illness without O. tsutsugamushi infection (n = 31) and in healthy controls (n = 31); all from the same area of South India. Results: Our main results were: (i) plasma DLL1 was markedly increased in scrub typhus patients at hospital admission with a significant decrease during recovery. (ii) RNA expression of NOTCH4 was decreased at admission in whole blood. (iii) A similar pattern for DLL1 and NOTCH4 was seen in febrile disease controls. (iv) Admission DLL1 in plasma was associated with disease severity and short-term survival. (vi) Regulation of Notch pathways in O. tsutsugamushi-infected monocytes as evaluated by public repository data revealed enhanced canonical Notch activation with upregulation of DLL1 and downregulation of NOTCH4. Conclusion: Our findings suggest that scrub typhus patients are characterized by enhanced canonical Notch activation. Elevated plasma levels of DLL1 were associated with organ dysfunction and poor outcomes in these patients. [ABSTRACT FROM AUTHOR]

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.

Introduction: Acute encephalitis syndrome (AES) is one of the important causes of mortality among children in India. Active management of the cases, followed by addressing the cause of AES, is the key strategy for preventing mortality. Lack of laboratory facility and difficulty of sampling blood and cerebrospinal fluid (CSF) for assessing causes is one of the important barriers to early initiation of treatment. The main objective of the study is to validate the Scrub Typhus Encephalitis Assessment Tool (SEAT) for the management of AES. Methods: The study is a continuation of a study conducted in a tertiary care hospital in Eastern Uttar Pradesh. A machine learning (LightGBM) model was built to predict the probability of scrub typhus diagnosis among patients with acute encephalitis. Three models were built: one with sociodemographic characters, the second with Model 1 variables and blood parameters, and the third with Model 2 variables and CSF parameters. Results: The sensitivity of diagnosing the scrub typhus case was 71%, 77.5%, and 83% in Model 1, Model 2, and Model 3, respectively, and specificity was 61.5%, 75.5%, and 76.3%, respectively, in the models. In Model 1 fever duration, in Models 2 and 3, neutrophil/lymphocyte ratio was the most important predictor for differentiating the scrub and nonscrub cases. Conclusion: With the available sensitivity and specificity of the tool, the SEAT can be a valuable tool for the prediction of scrub typhus as a cause of AES cases in remote areas.

Abstract Background Scrub typhus (ST, also known as tsutsugamushi disease) is a common febrile vector-borne disease in South Korea and commonly known as autumn- and female-dominant disease. Although understanding changes in seasonality and sex differences in ST is essential for preparing health interventions, previous studies have not dealt with variations in periodicity and demographic characteristics in detail. Therefore, we aimed to quantify the temporal dynamics of seasonal patterns and sex differences in the incidence of ST in South Korea. Methods We extracted epidemiological week (epi-week)-based ST cases from 2003 to 2019 Korean National Health Insurance Service data (ICD-10-CM code: A75.3). To determine changes in seasonality and sex differences, year-, sex-, and age-group-stratified male-to-female ratios and wavelet transform analyses were conducted. Results Between 2003 and 2019, 213,976 ST cases were identified. The incidence per 100,000 population increased by 408.8% from 9.1 in 2003 to 37.2 in 2012, and subsequently decreased by 59.7% from 2012 to 15.0 in 2019. According to the continuous wavelet transform results, ST exhibited a dual seasonal pattern with dominant seasonality in autumn and smaller seasonality in spring from 2005 to 2019. Overall, the periodicity of seasonality decreased, whereas its strength decreased in autumn and increased in spring. With an overall male-to-female ratio being 0.68:1, the ratio has increased from 0.67:1 in 2003 to 0.78:1 in 2019 (Kendall’s τ = 0.706, p

Coinfection with Dengue fever and Scrub Typhus presents significant diagnostic and therapeutic challenges, particularly in pediatric cases. We report a 6-year-old girl with fever, headache, maculopapular rash, and a vesicular lesion on the knee that progressed to a black eschar. She developed generalized edema, oral bleeding, decreased urine output, and renal dysfunction. Laboratory tests revealed anemia, leukocytosis, thrombocytopenia, elevated serum urea and creatinine, hypoalbuminemia, and hyponatremia. The Weil-Felix test was positive for OXK titer 1:320, and Dengue IgM antibodies were detected, complicating the diagnosis. Treatment with doxycycline, azithromycin, and local care for the eschar led to clinical improvement. This case highlights the importance of considering coinfection in febrile illnesses and emphasizes the need for accurate and timely diagnosis for effective management.

Rationale: Longitudinally extensive transverse myelitis (LETM) is a rare inflammatory demyelinating disease predominantly associated with autoimmune and inflammatory disorders. Scrub typhus can cause a variety of neurological complications, which may result in poor recovery and long-term disability. This report reveals a rare linkage between LETM and scrub typhus. Patient concerns: A 24-year-old female presented with a history of fever for 10 days associated with progressive quadriparesis. Physical examination revealed bilateral lower limb weakness (grade 0/5) and bilateral upper limb weakness (grade 2/5) with reduced sensation below the T3 dermatome. Diagnosis: Scrub typhus presenting with longitudinally extensive transverse myelitis. Interventions: Steroid pulse therapy with antibiotics supported by early intensive rehabilitation. Outcomes: Complete recovery was achieved. Lessons: This case report highlights the importance of considering scrub typhus as a potential cause of LETM in endemic regions, particularly in patients presenting with febrile illness and neurological symptoms.

Introduction: Scrub typhus is an important and widespread cause of acute febrile illness (AFI), which can be diagnosed easily by serological assay. Methods: All cases of AFI were sent for Scrub Typhus serology by rapid Enzyme Linked Immuno-Sorbent Assay (ELISA) method. Anyone found positive was admitted for further evaluation. Results: In this series 80 % had liver abnormality, 80 % had ARDS, 40 % had renal failure, 40 % had eschar and 80 % of them had MODS. Only 20 % had clinical features of encephalitis with MRI brain haemorrhagic transformation of infarct. All patients responded well to treatment with Doxycycline with hospitalization of around 7-10 days. Conclusion: This case series highlights the importance of keeping a high index of clinical suspicion to exclude scrub typhus in all AFI patients.

Purpose: Scrub typhus is a potentially life-threatening febrile illness associated with serious complications viz. pneumonia, acute respiratory distress syndrome, hepatic failure, acute kidney injury, encephalitis, and shock often culminating in mortality. We aimed to identify the predictors of mortality in scrub typhus. Methods: This prospective observational study was conducted in a tertiary referral hospital of the north Indian state of Uttarakhand on in-patients of scrub typhus hospitalized over 1 year Results: Of the 109 cases studied (54.1% males), 44% were aged

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.

Abstract Background Scrub typhus, caused by Orientia tsutsugamushi, rarely leads to central nervous system involvement. Although intracerebral bleeding is rare due to endemicity and a significant proportion of underdiagnoses, it should be considered a noteworthy differential diagnosis in endemic regions in patients with relevant history and clinical findings. Case presentation We present the case of a 40-year-old Nepali woman who visited the emergency department with complaints of left-sided weakness for 6 hours and an acute febrile illness with an eschar for 7 days and was diagnosed with scrub typhus by immunoglobulin M enzyme-linked immunosorbent assay of the serum. Imaging revealed a right-sided frontotemporal hematoma, and further examination revealed pulmonary edema with multiple organ dysfunction syndrome. The patient was mechanically ventilated and was treated with antibiotics, steroids, vasopressors, and antipyretics. However, the hematoma was treated conservatively, with ongoing neurological recovery at the 6-month follow-up. Conclusion Although neurological complications and intracranial hemorrhage are uncommon, physicians must be cautious when making differential diagnoses and initiating appropriate therapies to avoid serious or fatal complications.

At 3 severe infection cohort sites in Uganda, Orientia seropositivity was common. We identified 4 seroconversion cases and 1 PCR-positive case. These results provide serologic and molecular support for Orientia spp. circulating in sub-Saharan Africa, possibly expanding its endemic range. Orientia infections could cause severe illness and hospitalizations in this region.

Objective: Serological tests are widely used for scrub typhus diagnosis; however, their limitations are evident. This study aims to assess their practical value in clinical settings. Methods: We analyzed the data of adult patients with suspected scrub typhus who visited a tertiary care hospital in the Republic of Korea from September to December from 2019 to 2021. The included patients had an acute fever and at least one of the following ten secondary findings: myalgia, skin rash, eschar, headache, thrombocytopenia, increased liver enzyme levels, lymphadenopathy, hepatomegaly, splenomegaly, and pleural effusion. The diagnoses were grouped as scrub typhus or other diseases by two infectious disease physicians. Results: Among 136 patients who met the eligibility criteria, 109 had scrub typhus and 27 had different diseases. Single and paired total antibodies using immunofluorescence assay (IFA), and total antibodies using immunochromatography-based rapid diagnostic testing (ICT) were measured in 98%, 22%, and 75% of all patients, respectively. Confirmation using paired samples for scrub typhus was established at a median of 11 [interquartile range (IQR) 10-16] days following the first visit. Among the 82 admitted patients, the median admission time was 9 (IQR 7-13) days. According to IFA, 58 (55%) patients with scrub typhus had total immunoglobulin titers ≥1:320, while 23 (85%) patients with other disease had titers < 1:320. Positive ICT results were observed in 64 (74%) patients with scrub typhus and 10 (67%) patients with other diseases showed negative ICT results. Conclusions: Serological testing for scrub typhus is currently insufficient for decision-making in clinical practice.

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.

Background: Dengue fever and scrub typhus are endemic diseases in India. The aim was to study and compare clinical, biochemical, and hematological parameters between the dengue and dengue-scrub study groups. Materials and Methods: A retrospective hospital-based, cross-sectional study conducted at a tertiary care rural center. Various clinical, biochemical, and hematological parameters of dengue patients with random selection as the control group were compared with the dengue-scrub coinfection group (46 cases) as cases. The statistical significance was determined using an independent t-test. P < 0.05 was considered statistically significant. The t-test and the Mann–Whitney U-test were used. Results: Among the 86 cases (2.05%), scrub and dengue contributed 46 cases, followed by 27 cases of COVID-19 and dengue, four cases of malaria and scrub, three cases of malaria and dengue, and a single case of dengue with typhoid and leptospirosis with dengue. Serum albumin (P = 0.003, moderate effect size), serum globulin (P = 0.001, large effect size), alkaline phosphatase (P = 0.001, moderate effect size), and serum urea (P = 0.012, moderate effect size) levels were significantly different between only dengue and dengue-scrub group. In addition, the difference in hemoglobin levels, red blood cell count, white blood cell count, platelet count, cell variables, and ratios of those with dengue and scrub versus those with only dengue was significant (P < 0.05) with moderate-to-large effect size. Conclusion: Certain biochemical and hematological parameters such as albumin, globulin, alkaline phosphatase, platelet count, neutrophil-to-lymphocyte ratio, and platelet lymphocyte ratio can be used to support the diagnosis of coinfection (dengue-scrub).

Abstract Scrub typhus, a neglected disease, is a significant health concern in the Tsutsugamushi triangle of the Asia–Pacific and has raised global concerns due to recent cases occurring outside this region. To estimate the global prevalence of scrub typhus, we conducted a systematic review and meta-analysis. We conducted a systematic search of PubMed, Scopus, and Embase databases for observational studies on scrub typhus. Using a random-effects model, we combined the prevalence estimates with inverse-variance weights while also evaluating heterogeneity and publication bias. Among 3551 reports screened, we identified 181 studies with 1,48,251 samples for inclusion in our synthesis. The overall pooled seroprevalence (95% confidence intervals) of scrub typhus infections was 24.93% (23.27–26.60). Gender-wise pooled prevalence was estimated to be 50.23% (47.05–53.40) for males and 48.84% (45.87–51.80) for females. Eschar prevalence was observed to be 30.34% (22.54–38.15) among the positive cases. One-fourth of all the samples tested positive for scrub typhus and eschar was present in one-third of these total positive cases, encompassing regions beyond the Tsutsugamushi triangle. This estimation underlines the importance of this neglected disease as a public health problem. Strengthening surveillance and implementing disease control measures are needed in the affected regions.

Background: Scrub typhus, caused by Orientia tsutsugamushi, rarely leads to central nervous system involvement. Although intracerebral bleeding is rare due to endemicity and a significant proportion of underdiagnoses, it should be considered a noteworthy differential diagnosis in endemic regions in patients with relevant history and clinical findings. Case presentation: We present the case of a 40-year-old Nepali woman who visited the emergency department with complaints of left-sided weakness for 6 hours and an acute febrile illness with an eschar for 7 days and was diagnosed with scrub typhus by immunoglobulin M enzyme-linked immunosorbent assay of the serum. Imaging revealed a right-sided frontotemporal hematoma, and further examination revealed pulmonary edema with multiple organ dysfunction syndrome. The patient was mechanically ventilated and was treated with antibiotics, steroids, vasopressors, and antipyretics. However, the hematoma was treated conservatively, with ongoing neurological recovery at the 6-month follow-up. Conclusion: Although neurological complications and intracranial hemorrhage are uncommon, physicians must be cautious when making differential diagnoses and initiating appropriate therapies to avoid serious or fatal complications. [ABSTRACT FROM AUTHOR]

Figure depicts the sequential approach used for in-silico vaccine design and development and immune response prediction. [Display omitted] Scrub typhus, a potentially life-threatening infectious disease, is attributed to bacteria Orientia tsutsugamushi (O. tsutsugamushi). The transmission of this illness to humans occurs through the bite of infected chiggers, which are the larval forms of mites belonging to the genus Leptotrombidium. In this research, we developed a subunit vaccine specifically designed to target outer membrane proteins. Immunodominant cytotoxic T-lymphocytes (CTLs), B- lymphocytes (BCLs), and major histocompatibility complex (MHC)- II epitopes were identified using machine learning and bioinformatics approaches. These epitopes were arranged in different combinations with the help of suitable linkers like AAY, KK, GPGPG and adjuvant (cholera toxin B) that resulted in a vaccine construct. Physiochemical properties were assessed, where the predicted solubility (0.571) was higher than threshold value. Tertiary structure was predicted using I-TASSER web server and evaluated using Ramachandran plot (94 % residues in most favourable region) and z-score (−6.04), which had shown the structure to have good stability and residue arrangement. Molecular docking with immune receptors, Toll-like receptor (TLR)-2 and -4 showed good residue interaction with 13 and 5 hydrogen bonds respectively. Molecular dynamics simulations of receptor-ligand complex provided the idea about the strong interaction having 1.524751 × 10-5 eigenvalue. Amino acid sequence of vaccine was converted to nucleotide sequence and underwent codon optimization. The optimized codon sequence was used for in-silico cloning, which provided idea about the possibility of synthesis of vaccine using E. coli as host. Overall, this study provided a promising blueprint for a scrub typhus vaccine, although experimental validation is needed for confirmation. Furthermore, it is crucial to acknowledge that while bioinformatics provides valuable insights, in-vitro and in-vivo studies are imperative for a comprehensive evaluation of vaccine candidate. Thus, the integration of computational predictions with empirical research is essential to validate the efficacy, safety, and real-world applicability of the designed vaccine against Scrub Typhus. Nevertheless, the findings are good to carry forward for in-vitro and in-vivo investigations. [ABSTRACT FROM AUTHOR]

Objective: Defining whether a suspected case was due to scrub typhus through laboratory testing, to understand the prevalence of scrub typhus in Shijiazhuang City, Hebei Province. Methods: An epidemiological investigation was conducted on the suspected case, utilizing Weil-Felix test and indirect immunofluorescence assay (IFA) to detect specific antibodies against O. tsutsugamushi in serum specimens. Additionally, PCR amplification of the 56-kDa and groEL genes was performed, followed by constructing a phylogenetic tree to identify the genotype. Results: The acute phase titer of the Weil-Felix test for the case was 1:160, which increased to 1:320 in the recovery phase. IFA assay revealed IgG titers against O. tsutsugamushi of 1:64 in the acute phase and 1:256 in the recovery phase. Sequence alignment of the PCR amplified fragment showed the highest similarity with the O. tsutsugamushi genotype. Kawasaki sequence, ranging from 99.71 to 100.00%. The strain exhibited the closest genetic relationship with the known O. tsutsugamushi Kawasaki genotype. Conclusion: This study confirms the presence of O. tsutsugamushi in Shijiazhuang City, Hebei Province, with the identified strain belonging to the Kawasaki genotype, marking the first diagnosis of this strain in the region. [ABSTRACT FROM AUTHOR]

Background: Acute hepatitis due to various tropical infections can mimic the clinical picture of acute viral hepatitis(AVH), leading to increased morbidity and mortality. We aimed to identify clinical and laboratory parameters that could help to distinguish acute hepatitis due to tropical infections from AVH. Methods: We retrospectively analyzed our database of 150 children (107 boys) with AVH and 50 children(34 boys)with acute hepatitis due to tropical infections between January 2013 and March 2023. Clinical features, investigations, complications and outcomes were compared. Results: Hepatitis A (75%) was the commonest etiology of AVH while enteric fever (34%), dengue (26%), scrub typhus (20%) and leptospirosis (16%) constituted the majority of tropical infections. Persistent fever and skin rashes were found in 88% and 16% of patients respectively in the tropical infection group and none in the AVH group (p < 0.001). On univariate analysis, prodromal symptoms, clinically detectable jaundice, cholestatic pattern, total and direct bilirubin and liver enzymes were significantly higher in AVH while headache, myalgia, leukopoenia, thrombocytopenia, hyponatremia were significantly higher in tropical infections group (all p < 0.05). Multivariate analysis identified thrombocytopenia (Odds ratio [OR] 4.237) as an independent positive predictive factor and markedly elevated total bilirubin (OR 0.575), direct bilirubin (OR 0.498), aspartate aminotransferase (OR 0.841) and alanine aminotransferase (OR 0.863) as independent negative predictive factors for acute hepatitis due to tropical infections. Conclusion: High index of suspicion for tropical infections is warranted in patients with persistent fever after the onset of jaundice, especially in the presence of skin rash and thrombocytopenia. [ABSTRACT FROM AUTHOR]

Tsutsugamushi disease was first described in China by Hong Ge in 313. In his book Zhouhou Beiji Fang, three escharassociated febrile diseases were described: Shashidu, Zhongxidu, and Shegongdu. Shashidu was identified as being identical to tsutsugamushi disease in Japan: it occurred in riverside areas, exhibited an eschar, and was transmitted by tiny red “sand lice”. The nature of Zhongxidu remains unknown, but we propose that it is another type of Orientia tsutsugamushi infection: it occurred in mountainous areas, an eschar was observed, and the causative vector was not identified. Moreover, Zhongxidu would have predated Shashidu by five centuries; thus, the first documentation of tsutsugamushi disease would date back 2.2 millennia. O. tsutsugamushi infection without eschar has not been identified in ancient Chinese literature and may be included in Shanghan. Several ancient Chinese books describe that Shegongdu occurs following a Shegong bite. Shegong is described as a bug resembling a cockroach or cicada with a crossbow-like structure, possibly the hypostome and unfolded palps of tick, in its mouth. Thus, Shegong refers to an engorged tick and Shegongdu is a tick-borne rickettsiosis. However, due to a lack of entomological knowledge, these findings have not been recognized for the past 1.7 millennia. [ABSTRACT FROM AUTHOR]

Acute encephalitis syndrome (AES) outbreaks in children of Eastern Uttar Pradesh (E-UP) region of India have been a longstanding public health issue, with a significant case fatality rate of 20–25%. Since past decade, a rise in chikungunya (CHIK) cases has been occurring, which is a reported etiology of AES. However, the burden of chikungunya virus (CHIKV) among pediatric AES (pAES) is unknown from E-UP. We included 238 hospitalized pAES cases. The presence of IgM antibodies for CHIKV, and Dengue virus (DENV) was tested, and RT-PCR was performed for CHIKV and DENV in serologically confirmed CHIKV and DENV pAES cases. Positive samples were sequenced using Sangers sequencing. Further, to check for co-infection, IgM antibodies for other AES etiologies including Japanese encephalitis virus (JEV), Leptospira and Orientia tsutsugamushi (OT) in serum were also investigated. IgM ELISA demonstrated 5.04% (12) positivity for CHIKV. Among CHIKV IgM positive, 3 (25%, 3/12) pAES patients died. CHIKV genome was detected in 3 pAES specimens. Among which, 2 CHIKV cases were also positive for OT DNA. Partially sequenced CHIKV were genotyped as ECSA. The overall finding indicates evidence of CHIKV infection with high case fatality among pAES patients from E-UP. This study advocates constant serological and molecular surveillance of CHIKV in AES endemic regions of India. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Scrub typhus, a neglected disease, is a significant health concern in the Tsutsugamushi triangle of the Asia–Pacific and has raised global concerns due to recent cases occurring outside this region. To estimate the global prevalence of scrub typhus, we conducted a systematic review and meta-analysis. We conducted a systematic search of PubMed, Scopus, and Embase databases for observational studies on scrub typhus. Using a random-effects model, we combined the prevalence estimates with inverse-variance weights while also evaluating heterogeneity and publication bias. Among 3551 reports screened, we identified 181 studies with 1,48,251 samples for inclusion in our synthesis. The overall pooled seroprevalence (95% confidence intervals) of scrub typhus infections was 24.93% (23.27–26.60). Gender-wise pooled prevalence was estimated to be 50.23% (47.05–53.40) for males and 48.84% (45.87–51.80) for females. Eschar prevalence was observed to be 30.34% (22.54–38.15) among the positive cases. One-fourth of all the samples tested positive for scrub typhus and eschar was present in one-third of these total positive cases, encompassing regions beyond the Tsutsugamushi triangle. This estimation underlines the importance of this neglected disease as a public health problem. Strengthening surveillance and implementing disease control measures are needed in the affected regions. [ABSTRACT FROM AUTHOR]

Background: The existing literature lacks studies examining the epidemiological link between scrub typhus and deep vein thrombosis (DVT) or pulmonary embolism (PE), and the long-term outcomes. The objective of this study is to explore the potential association between scrub typhus and the subsequent risk of venous thromboembolism, and long-term mortality. Method: This nationwide cohort study identified 10,121 patients who were newly diagnosed with scrub typhus. Patients with a prior DVT or PE diagnosis before the scrub typhus infection were excluded. A comparison cohort of 101,210 patients was established from the general population using a propensity score matching technique. The cumulative survival HRs for the two cohorts were calculated by the Cox proportional hazards model. Result: After adjusting for sex, age, and comorbidities, the scrub typhus group had an adjusted HR (95% CI) of 1.02 (0.80–1.30) for DVT, 1.11 (0.63–1.93) for PE, and 1.16 (1.08–1.25) for mortality compared to the control group. The post hoc subgroup analysis revealed that individuals younger than 55 years with a prior scrub typhus infection had a significantly higher risk of DVT (HR: 1.59; 95% CI: 1.12–2.25) and long-term mortality (HR: 1.75; 95% CI, 1.54–1.99). Conclusion: The scrub typhus patients showed a 16% higher risk of long-term mortality. For those in scrub typhus cohort below 55 years of age, the risk of developing DVT was 1.59 times higher, and the risk of mortality was 1.75 times higher. Age acted as an effect modifier influencing the relationship between scrub typhus and risk of new-onset DVT and death. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus is a mite-borne zoonotic disease caused by Orientia tsutsugamushi and commonly presents with fever, rash, and eschar. Systemic complications develop later in the illness including, meningoencephalitis, pericardial effusion, myocarditis, and pneumonitis. In this article, we will be presenting different neurological manifestations of scrub typhus along with functional outcomes studied at a tertiary care center in New Delhi. Methods: This ambispective observational study was conducted at Army Hospital Research and Referral, New Delhi, during January 2018-January 2020. Febrile illness, serologically confirmed as scrub typhus and developing neurological complications were included. A predesigned clinical proforma was recorded for demographics, clinical features, neurological examination, supported with laboratory and/or radiology evaluation, and functional outcomes using the modified Rankin Scale (mRS). Results: In our cohort of 7 patients' majority were male (71%) with mean age at presentation being 42.5 years. Eschar was present in only 2 cases (28%) and a syndromic clinical diagnosis of meningoencephalitis was made in 3 (43%), acute flaccid quadriparesis in 2 (28%); and symptomatic seizure and parkinsonism in 1 patient each (14%). CSF showed lymphocytic pleocytosis with protein elevation in 57% cases. Systemic dysfunction was noted in the form of thrombocytopenia (57%), hyponatremia (42%), elevated transaminases (57%). Symptoms resolved with Doxycycline ± Rifampicin therapy in all cases, with good functional outcomes in majority of (89%) cases. Conclusion: Neurological complications in scrub typhus have a wide spectrum involving meninges, encephalon, basal ganglia, cranial, and peripheral nerves. High index of suspicion with early serological testing (ELISA) is a must in undifferentiated fevers. Timely initiation of appropriate therapy leads to good clinical outcomes, in majority of cases with neurological involvement. [ABSTRACT FROM AUTHOR]

Background and Objectives: Scrub typhus (ST) is detected in one-fourth of patients with acute febrile illnesses, confirming its nationwide re-emergence. The disease, if not diagnosed, can lead to multiple organ dysfunction and mortality. Being a vector-borne zoonotic disease, the molecular survey for pathogens in animal hosts is essential to predict the risk of its transmission to humans. Hence, this study aimed at identifying the effective animal tissue and molecular technique for zoonotic surveillance of ST infection in small animal hosts. Methods: Rodents/shrews were trapped from seventeen randomly selected villages in Puducherry between July and September, 2022. The presence of Orientia tsutsugamushi in ectoparasites and tissues including blood, lung, liver, spleen, kidney, heart, brain, and intestine retrieved from the animals was screened by nested PCR targeting 56 kDa, real-time PCR (qPCR) targeting 47 kDa and traD, and conventional PCR targeting groEL. The Weil–Felix test was carried out to detect antibodies against O. tsutsugamushi in rodent/shrew serum samples. Diagnostic accuracy measures of the molecular tests were calculated for each of the tissues by latent class modeling. Results:O. tsutsugamushi detected in the rodents/shrews were identified to be Karp-like and Kawasaki-like strains. Upon statistical analysis, qPCR targeting 47 kDa exhibited the highest accuracy measures in most of the tissues analyzed, with perfect sensitivity and specificity of 100% and 97% for intestine and lung samples for the epidemiological surveillance, respectively. Interpretation and Conclusion: The study recommends qPCR targeting 47 kDa gene and analysis of intestine and lung along with blood for the zoonotic surveillance of ST infection. [ABSTRACT FROM AUTHOR]

Background Scrub typhus is an understudied vector-borne bacterial infection. Methods We tested archived fever samples for scrub typhus seropositivity to begin charting its geographic distribution in Indonesia. We analysed 1033 serum samples from three sites. IgM and IgG enzyme-linked immunosorbent assay (ELISA) against Orientia tsutsugamushi was performed using Karp, Kato, Gilliam, TA 716 antigens. To determine the cutoff in the absence of a presumed unexposed population and gold standard tests, we identified the visual inflection point, performed change point analysis, and used finite mixture models. Results The optical density cutoff values used for IgM and IgG were 0.49 and 0.13, respectively. Across all sites, IgM seropositivity was 4.6% (95% CI: 3.4 to 6.0%) while IgG seropositivity was 4.4% (95% CI: 3.3 to 5.8%). The overall seropositivity across sites was 8.8% (95% CI: 8.1 to 11.7%). The overall seropositivity for Jambi, Denpasar, Tabanan were 9.7% (95% CI: 7.0 to 13.3%), 8.0% (95% CI: 5.7 to 11.0%), 9.0% (95% CI: 6.1 to 13.0%), respectively. Conclusions We conclude that O. tsutsugamushi exposure in humans occurred at all sites analysed and could be the cause of illness in some cases. Though it was not the main cause of acute fever in these locations, it is still important to consider scrub typhus in cases not responding to beta-lactam antibiotics. Future seroprevalence surveys and testing for scrub typhus in acute febrile illness studies will be essential to understand its distribution and burden in Indonesia. [ABSTRACT FROM AUTHOR]

Background Scrub typhus is a neglected life-threatening vector-borne disease mainly caused by the bacterium Orientia tsutsugamushi, which is occasionally transmitted to humans during feeding of larval mites. It has been estimated that more than 1 billion persons are potentially threatened and 1 million clinical cases occur annually across the world; however, it is unclear how this estimate was computed (and what the original source was) and much remains unknown regarding its global burden and risk factors. This systematic review aims to provide a comprehensive overview of the spatial-temporal distribution of scrub typhus, associated burden and risk factors at global, national and subnational resolutions, and to review the burden estimation models used at those different scales. Methods A systematic search for literature on scrub typhus occurrence, risk factors and modelling methods will be conducted. PubMed and five other databases will be searched for published literature, and Google Scholar and nine other databases will be used to search for grey literatures. All titles/abstracts of the searched records will be separately assessed by two reviewers, who will then screen the full-text of potential records to decide eligibility. A pre-formatted spreadsheet will be used by one reviewer to extract data from qualifying research, with a second reviewer checking the results. Data will be tabulated, synthesized descriptively, and summarized narratively for each review question. Where appropriate, meta-analyses will be conducted. The risk of bias will be assessed, and potential publication bias will be detected. Discussion This review will provide a comprehensive understanding of the current occurrence, spatial-temporal distribution, and burden of scrub typhus, identify associated risk factors from global to subnational resolutions, consolidate the best practice modeling framework(s) to estimate the burden of scrub typhus at various geographic/temporal resolutions, and decompose the relative contributions of various risk factors at scale. PROSPERO Registration CRD42022315209

Background: Scrub 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. Methods: NGS 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. Results: The 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. Conclusions: NGS 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.

BackgroundChina is one of the main epidemic areas of scrub typhus, and Zhejiang Province, which is located in the coastal area of southeastern China, is considered a key region of scrub typhus. However, there may be significant bias in the number of reported cases of scrub typhus, to the extent that its epidemiological patterns are not clearly understood. The purpose of this study was to estimate the possible incidence of scrub typhus and to identify the main driving components affecting the occurrence of scrub typhus at the county level.MethodsData on patients with scrub typhus diagnosed at medical institutions between January 2016 and December 2023 were collected from the China Disease Control and Prevention Information System (CDCPIS). The kriging interpolation method was used to estimate the possible incidence of scrub typhus. Additionally, a multivariate time series model was applied to identify the main driving components affecting the occurrence of scrub typhus in different regions.ResultsFrom January 2016 to September 2023, 2,678 cases of scrub typhus were reported in Zhejiang Province, including 1 case of reported death, with an overall case fatality rate of 0.04%. The seasonal characteristics of scrub typhus in Zhejiang Province followed an annual single peak model, and the months of peak onset in different cities were different. The estimated area with case occurrence was relatively wider. There were 41 counties in Zhejiang Province with an annual reported case count of less than 1, while from the estimated annual incidence, the number of counties with less than 1 case decreased to 21. The average annual number of cases in most regions fluctuated between 0 and 15. The numbers of cases in the central urban area of Hangzhou city, Jiaxin city and Huzhou city did not exceed 5. The estimated random effect variance parameters σλ2, σϕ2, and σν2 were 0.48, 1.03 and 3.48, respectively. The endemic component values of the top 10 counties were Shuichang, Cangnan, Chun’an, Xinchang, Pingyang, Xianju, Longquan, Dongyang, Yueqing and Qingyuan. The spatiotemporal component values of the top 10 counties were Pujiang, Anji, Pan’an, Dongyang, Jinyun, Ninghai, Yongjia, Xiaoshan, Yinwu and Shengzhou. The autoregressive component values of the top 10 counties were Lin’an, Cangnan, Chun’an, Yiwu, Pujiang, Longquan, Xinchang, Luqiao, Sanmen and Fuyang.ConclusionThe estimated incidence was higher than the current reported number of cases, and the possible impact area of the epidemic was also wider than the areas with reported cases. The main driving factors of the scrub typhus epidemic in Zhejiang included endemic components such as natural factors, but there was significant heterogeneity in the composition of driving factors in different regions. Some regions were driven by spatiotemporal spread across regions, and the time autoregressive effect in individual regions could not be ignored. These results that monitoring of cases, vectors, and pathogens of scrub typhus should be strengthened. Furthermore, each region should take targeted prevention and control measures based on the main driving factors of the local epidemic to improve the accuracy of prevention and control.

Objectives: Scrub 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. Methods: We 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. Results: We 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. Conclusions: Our comprehensive review elucidates the significant yet variable burden of scrub typhus across different regions, underscoring its emergence as a critical public health concern globally.

Aim and background: Tropical infections have a high prevalence in India. Mostly, coinfection with more than one tropical infection makes the diagnosis difficult and increases mortality and morbidity. To increase more awareness regarding tropical infections which can turn into life threatening situations and the need for aggressive management for that. Case description: We present a case of a 51-year-old lady admitted with vomiting and diarrhea, which rapidly progressed into sepsis and multiorgan dysfunction. Blood investigations showed coinfection with hepatitis E, scrub typhus, and dengue. She was treated aggressively with all conservative and interventional measures. Conclusion: Despite our best efforts, she had a persistent high-grade fever, severe anemia, thrombocytopenia, and markedly increased liver enzymes with raised D-dimer, fibrinogen, and ferritin, leading to secondary hemophagocytic lymphohistiocytosis (HLH) syndrome. She succumbed to the illness ultimately. Clinical significance: triple coinfection of dengue, hepatitis E, and scrub typhus, which, to our knowledge, has not been previously reported in the literature, making it an exceptionally rare presentation. [ABSTRACT FROM AUTHOR]

AbstractIntroductionCase reportConclusionsHere we report a child of Gullian Barre syndrome (GBS) with opisthotonic posturing and we subsequently detected Scrub typhus in him.An 11-year-old boy presented with progressive motor quadriparesis with transient bladder retention, bilateral facial weakness, diminished gag reflex, absent reflexes and his nerve conduction studies suggested Acute Motor Axonal Neuropathy (AMAN) GBS. His power gradually started recovering after one week. However, he had opisthotonus and signs of meningeal irritation. The child’s CSF examination was consistent with GBS. His bacterial, fungal, tubercular microscopy and cultures and viral markers were negative. IgM for Borrelia and Leptospira and HIV ELISA were negative. IgM for scrub typhus, however, came out to be positive. Hence, we gave him azithromycin and he recovered almost completely in 3 months.To our knowledge there is no previous report of opisthotonic posturing in GBS patients. This could be due to radicular involvement in immune mediated etiology of GBS. [ABSTRACT FROM AUTHOR]

Abstract Background Scrub typhus is an acute infectious disease caused by Orientia tsutsugamushi. Guillain–Barre syndrome (GBS) is an autoimmune-mediated peripheral neuropathy with a frequent history of prodromal infections, but GBS associated with scrub typhus is very rare. Case presentation We report a 51-year-old male patient who developed dysarthria and peripheral facial paralysis following the cure of scfrub typhus. CSF examination and electrophysiological findings suggested a diagnosis of GBS. After treatment with intravenous immunoglobulin, the patient’s neurological condition improved rapidly. Conclusions Scrub typhus infection is likely to be a potential predisposing factor in GBS, while scrub typhus-associated GBS has a favorable prognosis.

Abstract Background Trombiculid mites are globally distributed, highly diverse arachnids that largely lack molecular resources such as whole mitogenomes for the elucidation of taxonomic relationships. Trombiculid larvae (chiggers) parasitise vertebrates and can transmit bacteria (Orientia spp.) responsible for scrub typhus, a zoonotic febrile illness. Orientia tsutsugamushi causes most cases of scrub typhus and is endemic to the Asia-Pacific Region, where it is transmitted by Leptotrombidium spp. chiggers. However, in Dubai, Candidatus Orientia chuto was isolated from a case of scrub typhus and is also known to circulate among rodents in Saudi Arabia and Kenya, although its vectors remain poorly defined. In addition to Orientia, chiggers are often infected with other potential pathogens or arthropod-specific endosymbionts, but their significance for trombiculid biology and public health is unclear. Results Ten chigger species were collected from rodents in southwestern Saudi Arabia. Chiggers were pooled according to species and screened for Orientia DNA by PCR. Two species (Microtrombicula muhaylensis and Pentidionis agamae) produced positive results for the htrA gene, although Ca. Orientia chuto DNA was confirmed by Sanger sequencing only in P. agamae. Metagenomic sequencing of three pools of P. agamae provided evidence for two other bacterial associates: a spirochaete and a Wolbachia symbiont. Phylogenetic analysis of 16S rRNA and multi-locus sequence typing genes placed the spirochaete in a clade of micromammal-associated Borrelia spp. that are widely-distributed globally with no known vector. For the Wolbachia symbiont, a genome assembly was obtained that allowed phylogenetic localisation in a novel, divergent clade. Cytochrome c oxidase I (COI) barcodes for Saudi Arabian chiggers enabled comparisons with global chigger diversity, revealing several cases of discordance with classical taxonomy. Complete mitogenome assemblies were obtained for the three P. agamae pools and almost 50 SNPs were identified, despite a common geographic origin. Conclusions P. agamae was identified as a potential vector of Ca. Orientia chuto on the Arabian Peninsula. The detection of an unusual Borrelia sp. and a divergent Wolbachia symbiont in P. agamae indicated links with chigger microbiomes in other parts of the world, while COI barcoding and mitogenomic analyses greatly extended our understanding of inter- and intraspecific relationships in trombiculid mites.

Objectives: To study epidemiological characteristics, clinical features, laboratory findings, and clinical outcomes in cases of scrub typhus. Additionally, the study aims to identify the predictors of disease severity. Methods: This cross-sectional study was conducted in the Department of General Medicine at Dr PDM Medical College in Amaravati, India. The study duration was 6 months, from July 2023 to December 2023. All clinically confirmed patients with scrub typhus were evaluated through history, clinical examination, and appropriate laboratory investigations. The clinical and laboratory profiles, hospital course, and outcomes were analyzed. Organ dysfunction upon admission was assessed using the sequential organ failure assessment (SOFA) score. Results: A total of 200 cases were included in the study. The majority of the cases were in the age range of 31-40 years, and most of them were males. The highest number of scrub typhus cases occurred in September. The most common presenting symptoms were fever (81%), followed by nausea (37.5%), generalized weakness (34%), abdominal pain, eschar (21.5%), breathlessness, and cough (21% each), headache (19%), vomiting (15%), and altered sensorium (4.5%). The majority of patients (72.5%) did not experience any complications, while 55 patients (27.5%) developed multi-organ dysfunction syndrome (MODS) as a complication. The mortality rate was 1%. Conclusion: Scrub typhus is a significant cause of acute febrile illness in the Vidarbha region of Maharashtra. It can present with various clinical manifestations, with or without an eschar. Early diagnosis and appropriate treatment of these cases can lead to minimal complications.

Objectives: We conducted a systematic analysis of the notifiable rickettsial diseases in humans in China during 1950-2022. Methods: We utilized descriptive statistics to analyze the epidemiological characteristics, clinical manifestations, and diagnostic characteristics of typhus group rickettsiosis (TGR) and scrub typhus (ST) cases. Results: Since the 1950s, there have been variations in the incidence rate of TGR and ST in China, with a downtrend for TGR and an uptrend for ST. The South became a high-incidence area of TGR, whereas the North was previously the high-incidence area. ST cases were concentrated in the South and the geographic area of ST spread northward and westward. The seasonality of TGR and ST were similar in the South but distinct in the North. Most TGR and ST cases were reported by county-level medical institutions, whereas primary institutions reported the least. Delayed diagnosis was associated with fatal outcomes of TGR and ST. Cases in low-incidence provinces, confirmed by laboratory tests and reported from county/municipal-level institutions had higher odds of delayed diagnoses. Conclusions: Our study revealed significant changes in the epidemiological characteristics of TGR and ST in China, which can provide useful information to enhance the control and prevention strategies of rickettsial diseases in China.