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Human granulocytic anaplasmosis (HGA) is a tick-borne infection caused by Anaplasma phagocytophilum. Only seven cases of HGA have been reported in Japan to date. We report the case of a 61-year-old female farmer who developed HGA with rash and rhabdomyolysis. The patient had fever and erythema covering the entire body, including the palms. An induration with an eschar was observed on the right leg, indicating that the patient had been bitten by a tick. Elevated serum creatinine and creatinine kinase levels and hematuria indicated rhabdomyolysis. We suspected Japanese spotted fever, a tick-borne illness caused by Rickettsia Japonica , and administered minocycline and ciprofloxacin for a week. Transient neutropenia and thrombocytopenia were observed, but the symptoms improved. Polymerase chain reaction (PCR) and antibody tests for R. japonica and Orientia tsutsugamushi , which causes scrub typhus, were both negative. The PCR test for severe fever with thrombocytopenia syndrome virus was also negative. Antibodies against A. phagocytophilum –related proteins were detected by western blotting, indicating seroconversion of IgG with paired serum samples, and the patient was diagnosed with HGA. HGA should be suspected in acute febrile patients with a history of outdoor activity and cytopenia, with or without a rash. A testing system and the accumulation of cases in Japan are necessary for the early diagnosis and appropriate treatment of HGA. [ABSTRACT FROM AUTHOR]

AbstractGraphene quantum dots (GQDs) were used for surface modification of a screen-printed paper electrode (SPPE) for the development of a mobile phone-integrated immunosensor for the detection of scrub typhus. GQDs were synthesized from a 1.8% starch solution via a hydrothermal method and characterized by ultraviolet–visible (UV–Vis) spectroscopy, fluorescence, Fourier transform infrared spectroscopy and dynamic light scattering. Furthermore, anti-56 kDa type specific antigen (TSA) antibodies were used for immobilization on the GQD-modified SPPE working electrode using EDC/NHS (N-ethyl-N′-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) (1:1) chemistry. The TSA antigen was used at different concentrations to interact with specific antibodies, and the response was recorded via cyclic voltammetry, differential pulse voltammetry and electrochemical impedance spectroscopy using potassium ferricyanide K4[Fe(CN)6]− as a redox indicator. The developed immunosensor showed an excellent sensitivity of 17.40 µA cm−2 ng−1 and a limit of detection of 0.399 ng µL−1. The developed immunohybrid sensor is a novel mobile phone-integrated, highly specific and stable platform for Orientia tsutsugamushi. [ABSTRACT FROM AUTHOR]

Wild rodents and their ectoparasites are known reservoirs for various zoonotic pathogens, highlighting the need for detailed studies into their roles in disease transmission. Our research investigated the spatial distribution of rodents and their ectoparasites to better understand the epidemiology of vector‐borne zoonotic diseases (VBZDs), including severe fever with thrombocytopenia syndrome (SFTS), Lyme disease, Q fever, and scrub typhus. We analyzed samples from 540 rodents and 6785 mites, detecting the presence of Borrelia spp., the causative agent of Lyme disease, in 0.9% of rodents and SFTS virus (SFTSV) in 1.0%. In mites, Borrelia spp. and Orientia tsutsugamushi, the bacteria causing scrub typhus, were detected in 0.3% of samples each. Phylogenetic analysis identified the SFTSV sequence as type B3, the Borrelia spp. sequence as B. afzelii, and the O. tsutsugamushi sequence as Karp‐related. Notably, SFTSV was detected for the first time in mites in South Korea, and B. afzelii was found in mites for the first time globally. These findings emphasize the critical need for continuous analysis of VBZDs to anticipate future trends and develop a comprehensive monitoring system. Further research into the rodent and mite populations in South Korea is essential to fully assess the potential risks of VBZDs. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus is a common rickettsial infection endemic in India and is an important cause of acute febrile illness among children. Clinical manifestations vary from mild-to-severe affecting almost all organ systems with a high fatality rate. To reduce morbidity and mortality, a high index of suspicion, timely diagnosis, and treatment are crucial. However, due to lack of awareness, low index of suspicion among clinicians, and non-specific clinical presentation which overlaps with other tropical endemic infections of India such as dengue, chikungunya, malaria, and leptospirosis, scrub typhus is often underdiagnosed in our country. Aims and Objectives: (1) To find the prevalence of scrub typhus among children presenting with fever for the last 5 days, (2) To study their clinico-demographic profiles. Materials and Methods: Blood collected from children aged 1 month to 12 years of age presenting with fever for the last 5 days were tested for scrub typhus immunoglobulin M enzyme-linked immunosorbent assay. Clinical characteristics and laboratory parameters of the patients were collected. The results obtained were analyzed and interpreted. Results: Out of 865 pediatric patients presenting with fever, only 227 (26.24%) were positive for scrub typhus. Maximum cases (45.37%) were found in the age group >5-12 years. Fever was the presenting feature in all the cases. Other common presentations were hepatosplenomegaly, lymphadenopathy, pain abdomen, rash, and eschar. Conclusion: Although scrub typhus is an easily treatable disease, timely diagnosis and treatment are needed to avoid complications which require a high degree of suspicion among clinicians along with a robust laboratory setup with adequate diagnostic facilities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Chiggers are the exclusive vector of scrub typhus. A total of 61 chigger species were identified from Apodemus latronum, which is an endemic mouse species in southwest China. There was an age bias; adult A. latronum had higher infestation indices of chiggers (PM = 38.28%, MA = 5.11) than juvenile mice (PM = 12.63%, MA = 0.97). The mouse hosts with poor nutrition had higher chigger infestation indices than the hosts with good nutrition. The chigger infestation obviously fluctuated along different altitude gradients, and the β diversity of the chigger community showed a gradually increasing tendency from the low to high altitudes. The dominant chigger species had high spillover potentials, dispersing from high to low altitudes. The temperature and humidity are the most important factors influencing the chigger infestation. Chiggers are the exclusive vector of Orientia tsutsugamushi, which is the causative agent of scrub typhus. Based on the field surveys in southwest China between 2001 and 2022, this paper retrospectively reported the chigger infestation and distribution on the large-eared field mouse (Apodemus latronum), an endemic rodent species in the region, for the first time. A total of 933 chiggers were collected from 501 mice, and these chiggers were identified as 2 families, 8 genera, and 61 species. The overall infestation prevalence (PM) and mean abundance (MA) of A. latronum with chiggers reached 19.76% and 1.86 mites/per mouse, respectively. The chigger infestation indices on adult A. latronum (PM = 38.28%, MA = 5.11) were higher than those on juvenile mice (PM = 12.63%, MA = 0.97) with p < 0.01, showing an age bias of infestation. The relative fatness (K) was used to reflect the nutrition status of the mouse host. The mouse hosts with good nutrition (K = 3.4 ± 0.89 g/cm3) harbored fewer chiggers than the hosts with poor nutrition (K = 2.2 ± 0.90 g/cm3) (p < 0.01). The infestation indices of chiggers on A. latronum obviously fluctuated along different altitude gradients (p < 0.01). With the increase in altitudes, the β diversity of the chigger community showed a gradually increasing tendency. The spillover chord diagram, which was based on indices of PAC (potential for apparent competition), revealed high spillover potentials of dominant chigger species dispersing from high altitude gradients to the lowest one. The chigger abundance was positively correlated with the mean monthly temperature (tmp), mean monthly humidity (hum), the mean monthly precipitation (pre), and the human footprint (hfp), and it was negatively correlated with the altitude (ele) (p < 0.05). The temperature and humidity are the most important factors which influence the chigger infestation. [ABSTRACT FROM AUTHOR]

Background: Thromboembolic events are a well-recognized cause of in-hospital deaths of patients with infectious diseases. However, thromboembolic events in patients with scrub typhus, caused by Orientia tsutsugamushi have rarely been reported. This study aimed to assess risk factors associated with thromboembolic events in patients with scrub typhus. Methods: All 93 scrub typhus patients' diagnoses were confirmed serologically or by positive nested polymerase chain reaction (PCR). The clinical and laboratory findings from 12 scrub typhus patients with thromboembolic events and 81 scrub typhus patients with nonthromboembolic events were retrospectively studied. To determine the factors implicated in thromboembolic events, we performed multivariate logistic regression analysis using the six independent factors identified by the univariate analysis. Findings: The mean age of the patients in the thromboembolic group was 76.4 years (median, 76 years), and in nonthromboembolic group it was 64.6 years (median, 65 years) (P<0·001). Thromboembolic events were observed in 12 patients. These events included acute coronary syndrome (n = 5), acute limb ischemia (n = 4), ischemic stroke (n = 1), deep vein thrombosis combined with pulmonary thromboembolism (n = 1), and left common iliac artery aneurysm with a thrombus (n = 1). According to multivariate analysis, the following four factors were significantly associated with the thromboembolic events: 1) treatment with rifampin (OR = 57.6; CI 1.2–2700.3), 2) Taguchi genotype (OR = 41.5, P = 0.028; CI 1.5–1154.6), 3) atrial fibrillation (OR = 9.4, P = 0.034; CI 1.2–74.0), and 4) age (OR = 1.1, P = 0.046; CI 1.0–1.3). Conclusions: Our study suggests that clinicians should be cautious when managing patients with scrub typhus to avoid the development of thromboembolic events, especially in patients with risk factors such as treatment with rifampin, Taguchi genotype, atrial fibrillation, and advanced age. Author summary: Scrub typhus, a disease caused by Orientia tsutsugamushi, is typically treated with antibiotics. It can sometimes lead to serious complications, including thromboembolic events. These events can be life-threatening but have been rarely reported due to under-suspicion in clinical practice, as their rarity often leads to them being overlooked. In this regard, our study suggests that clinicians should be cautious when managing patients with scrub typhus to prevent the development of thromboembolic events, especially in patients with risk factors such as treatment with rifampin, Taguchi genotype, atrial fibrillation, and advanced age. [ABSTRACT FROM AUTHOR]

Rickettsiosis includes a diversity of culture-negative non-specific systemic infections. Laboratory diagnosis of rickettsiosis is often not easy. In this 12-month study, six patients with a variety of rickettsia infections of the spotted fever group, typhus group and scrub typhus were diagnosed directly or indirectly by metagenomic next-generation sequencing (mNGS). The patient with Japanese spotted fever was rapidly made when mNGS analysis of the patient's blood revealed Rickettsia japonica sequences. For the two patients with Rickettsia felis chest infections, the bacterium was detected in the bronchoalveolar lavage of one case and lung biopsy of the other. Both patients had underlying malignancies, carcinoma of the breast and carcinoma of the lung respectively, and were on chemotherapy with immunosuppressive effect. For the remaining three patients who presented over a period of 13 weeks, all had fever, headache and the typical eschar. They also had increased serum transaminases and responded promptly to doxycycline. However, the Weil-Felix test results of all three patients were negative. Since we considered the three cases typical of rickettsiosis, we submitted their serum samples for mNGS analysis. Results showed that Orientia tsutsugamushi sequences were present in the serum of one case. In view of the positive mNGS results, we repeated the Weil-Felix test for the residual sera of all three patients and it revealed that those of the other two cases showed OX-19 titers of 1:640 and 1:160 respectively, inferring that these two patients probably had rickettsiosis of the typhus group. As for the patient positive for O. tsutsugamushi sequences, we also detected IgM for O. tsutsugamushi in the serum, which double confirmed that it was a case of scrub typhus. mNGS is an important molecular tool and can complement serology for laboratory diagnosis of rickettsiosis. Author summary: Rickettsiosis includes a diversity of systemic infections presented with non-specific symptoms. Laboratory diagnosis of rickettsiosis is often not easy. In this 12-month study, six patients with a variety of rickettsia infections were diagnosed directly or indirectly by metagenomic next-generation sequencing (mNGS). These include one patient with Japanese spotted fever in whom Rickettsia japonica sequences were detected in blood, two patients with Rickettsia felis chest infections in whom R. felis sequences were detected in respiratory samples, one patient with scrub typhus in whom Orientia tsutsugamushi sequences were detected in serum, and two patients with rickettsiosis of the typhus group. In particular, the last three patients had initial false-negative Weil-Felix test results performed in a central reference laboratory but the diagnosis of rickettsiosis was subsequently confirmed by mNGS and repeated serology. mNGS is an important diagnostic tool for rickettsiosis and other difficult-to-diagnose systemic infections. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus, a zoonotic disease, is transmitted to humans by the bite of larval trombiculid mite. Keeping in view the morbidity and mortality associated with undiagnosed cases (due to both lack of specific diagnostic tests and ignorance about the disease), the disease deserves a special mention. Aims and Objectives: The aims and objectives of the study were to assess complications and atypical manifestations of scrub typhus fever in this subpopulation and to assess the prognosis of patients presenting with atypical manifestations/ complications. Materials and Methods: This is a longitudinal observational study on the basis of clinical and laboratory evidence at Department of Pediatrics, Calcutta-National-Medical College and Hospital, Kolkata, West Bengal, from March 2021 to February 2022. Children between >28 days and <12 years with atypical manifestations of scrub typhus who were scrub immunoglobulin (Ig)M positive (Serum and/or cerebrospinal fluid) were included in the study. Results: Of the 120 scrub typhus IgM-positive patients admitted in 1 year, complications present in 35%. These patients developed encephalitis, encephalomyelitis, neurological deficits, myocarditis, disseminated intravascular coagulation, acute kidney injury, atypical pneumonia, acute respiratory distress syndrome, acute encephalitis syndrome (23.8%), myocarditis with/without heart failure (14.3%), and multi-inflammatory syndrome in children with/without severe acute respiratory syndrome coronavirus 2 IgG (14.2%). There is a statistically significant association between the duration of fever at admission and pediatric intensive care unit (PICU) admission, the longer the fever duration at admission, the higher the rate of complications and thus PICU admission. Conclusion: Scrub typhus infection has expanded its various forms, presenting in various atypical manifestations alongside the common clinical features. Multiple cases of multiorgan involvement in the form of multi-inflammatory syndrome and hemophagocytic lymphohistiocytosis have been reported in the background of COVID-19 infection, alongside a significant percentage of scrub typhus infection reported in infancy. Thus, early detection is important to start intervention. [ABSTRACT FROM AUTHOR]

Simple Summary: Chiggers are common ectoparasites on rodents and other small mammals, and they transmit scrub typhus, a zoonotic disease. Dehong in Yunnan Province of southwest China is located on the China–Myanmar border, and it is a focus of scrub typhus. The present paper reports the infestation and distribution of chiggers on small mammals in Dehong for the first time. From 1760 rodents and other sympatric small mammals, a total of 9309 chiggers were identified, representing 117 species. Most chigger species had low host specificity. Leptotrombidium deliense, a major vector of scrub typhus in China, was the dominant chigger species in Dehong, and it was mainly distributed in flatland areas and indoors. The infestation and community indexes of chiggers in mountainous areas and outdoors were higher than those in flatland areas and indoors. The species abundance distribution of the chigger community conformed to log-normal distribution, and the total number of chigger species was roughly estimated to be 147. The species diversity of the chigger community is high in Dehong, with an obvious environmental heterogeneity. The low host specificity of chiggers and the occurrence of a large number of L. deliense in Dehong would increase the transmission risk of scrub typhus on the China–Myanmar border. Chiggers (chigger mites) are a group of tiny arthropods, and they are the exclusive vector of Orientia tsutsugamushi (Ot), the causative agent of scrub typhus (tsutsugamushi disease). Dehong Prefecture in Yunnan Province of southwest China is located on the China–Myanmar border and is an important focus of scrub typhus. Based on the field surveys in Dehong between 2008 and 2022, the present paper reports the infestation and ecological distribution of chiggers on the body surface of rodents and other sympatric small mammals (shrews, tree shrews, etc.) in the region for the first time. The constituent ratio (Cr), prevalence (PM), mean abundance (MA), and mean intensity (MI) were routinely calculated to reflect the infestation of small-mammal hosts with chiggers. Additionally, the species richness (S), Shannon–Wiener diversity index (H), Simpson dominance index (D), and Pielou's evenness index (E) were calculated to illustrate the chigger community structure. Preston's log-normal model was used to fit the theoretical curve of species abundance distribution, and the Chao 1 formula was used to roughly estimate the expected total species. The "corrplot" package in R software (Version 4.3.1) was used to analyze interspecific relationships, and the online drawing software was used to create a chord diagram to visualize the host–chigger associations. From 1760 small-mammal hosts, a total of 9309 chiggers were identified as belonging to 1 family, 16 genera, and 117 species, with high species diversity. The dominant chigger species were Leptotrombidium deliense, Walchia ewingi, and Gahrliepia longipedalis, with a total Cr = 47.65% (4436/9309), among which L. deliense is the most important vector of Ot in China. The overall infestation indexes (PM, MA, and MI) and community parameters (S, H, and E) of chiggers in the mountainous areas and outdoors were higher than those in the flatland areas and indoors, with an obvious environmental heterogeneity. Leptotrombidium deliense was the dominant species in the flatland and indoors, while G. longipedalis was the prevalent species in the mountainous and outdoor areas. The species abundance distribution of the chigger community conformed to log-normal distribution with the theoretical curve equation: S (R) ′ = 28 e − [ 0.23 (R − 0) ] 2 , indicating the existence of many rare species and only a few dominant species in the community. The expected total number of chigger species was roughly estimated to be 147 species, 30 more than the 117 species actually collected, suggesting that some uncommon species may have been missed in the sampling survey. The host–parasite association analysis revealed that one host species can harbor different chigger species, and one chigger species can parasitize different host species with low host specificity. A positive or negative correlation existed among different chigger species, indicating a cooperative or competitive interspecific relationship. The species diversity of chiggers is high in Dehong on the China–Myanmar border, and a large host sample is recommended to find more uncommon species. There is an obvious environmental heterogeneity of the chigger community, with different species diversity and dominant species in different environments. The low host specificity of chiggers and the occurrence of a large number of L. deliense in Dehong, especially in flatland areas and indoors, would increase the risk of persistent transmission of scrub typhus in the region. [ABSTRACT FROM AUTHOR]

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]

Background:Rickettsia spp. are vector-borne zoonotic pathogens that cause febrile illness in humans. Rickettsioses is not included in the Colombian national surveillance system and is subsequently expected to be underreported. This cross-sectional study aimed to determine the seroprevalence of Rickettsia spp. and the closely related Orientia tsutsugamushi in two indigenous populations residing in the Sierra Nevada de Santa Marta, Colombia. Materials and Methods: Serum samples (n = 539) were collected from the Wiwa and Koguis people between 2021 and 2022. Serum samples were screened for spotted fever group (SFG) and typhus group (TG) Rickettsia spp. using the Fuller laboratories Rickettsia IgG IFA kit and for O. tsutsugamushi with the Scrub Typhus Detect™ IgG ELISA. Results: We observed an overall seroprevalence of 26.2% (95% confidence interval [CI] 22.5–30.1] for Rickettsia spp. of the SFG, 5.4% (95% CI 3.6–7.6) for Rickettsia spp. of the TG and 4.3% (95% CI 2.7–6.3) for O. tsutsugamushi. Common risk factors for zoonotic disease infections were assessed for 147 of the Wiwa participants. Increased odds of seropositivity for SFG Rickettsia spp. were observed for Wiwa participants who cared for livestock, including assisting with the birth of cattle (odds ratio [OR] = 8.85; 95% CI 1.54–50.90; p = 0.015) and goats (OR = 7.60; 95% CI 1.70–33.90; p = 0.008). Conclusions: These results highlight a notable exposure to Rickettsia spp., especially the SFG, in rural Colombia. Together with recent reports of high mortality for Rocky Mountain Spotted Fever in nearby regions of South America, more detailed investigations focusing on improving knowledge and awareness as well as "One Health" and "causes-of-fever" studies are needed. The characterization of Rickettsia spp. infections in humans, livestock, and tick vectors with their potential transmission routes could make a high impact on these easily treatable diseases. [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]

Scrub typhus is caused by the Gram-negative obligate intracellular bacterium Orientia tsutsugamushi, and this tick-borne disease is difficult to distinguish from other acute febrile illnesses as it typically presents with symptoms such as rash, crusting at the bite site, headache, myalgia, lymphadenopathy, and elevated liver transaminases. It can often be diagnosed clinically, but not all patients present with characteristic symptoms, so serological diagnosis and molecular techniques may be required. However, existing diagnostic tests often have low sensitivity and specificity, making early detection difficult. This study presents a nucleic acid extraction method using large volumes of plasma and buffy coat to increase sensitivity, as well as an improved detection method using two target genes. Using the I-PULL device, nucleic acids can be extracted from up to 4 mL of sample in 30 min, avoiding contamination. The extracted DNA detects two genes of O. tsutsugamushi, increasing sensitivity compared to single-gene detection. Clinical validation in 38 patient samples showed 100% specificity and 95.24% sensitivity for the single target gene, with specificity and sensitivity rising to 100% when both genes are analyzed. This molecular diagnostic platform can be useful for distinguishing scrub typhus from similar diseases. [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]

Objective To establish a nomogram model for tsutsugamushi disease complicated with sepsis based on Lasso regression, so as to provide a reference for the diagnosis and treatment of tsutsugamushi disease complicated with sepsis. Methods We selected patients with scrub typhus patients admitted to Kunming Third People’s Hospital from June 2012 to December 2023 as the research subjects (n = 235), with scrub typhus patients patients with sepsis as the experimental group (n = 138) and scrub typhus patients patients without sepsis as the control group (n = 97), Lasso regression was used to screen the influencing factors of scrub typhus combined with sepsis, and a nomogram model was constructed through logistic regression. The effectiveness of the model was evaluated using receiver operating characteristic (ROC) curves and calibration curves, and clinical utility analysis was performed using decision curve analysis (DCA). Results The results of multivariate analysis through logistic regression showed: that age (OR = 1.039, 95%CI: 1.017～1.061), PLT (OR = 0.995, 95%CI: 0.990～1.000), UA (OR = 1.004, 95%CI: 1.001 ～1.008) and IgA (OR = 0.680, 95%CI: 0.472 ～0.979) were independent influencing factors of scrub typhus combined with sepsis. The area under the ROC curve (AUC) was 0.721 (95%CI: 0.656～0.786, P < 0.001), the sensitivity of the model was 69.1%, and the specificity was 63.1%. The calibration curve indicates that the model had good consistency, and the DCA indicated that the model had a high net benefit value. Conclusion Patients with scrub typhus are associated with increased age and UA levels and decreased PLT and IgA levels, and have a higher risk of secondary sepsis. [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]

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]

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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]

Spotted fever group (SFG) rickettsia, the causative agent of SFG rickettsiosis, is predominantly carried by ticks, whereas Orientia tsutusgamushi, the causative agent of scrub typhus, is primarily transmitted by chigger mites in Japan. In this study, we attempted to isolate intracellular eubacteria from Leptotrombidium scutellare, a major vector of O. tsutsugamushi; moreover, we isolated an SFG rickettsia using a mosquito‐derived cell line. Draft genome sequences of this unique isolate, by applying criteria for species delimitation, classified this isolate as a novel strain, proposed as "Rickettsia kedanie." Further genetic analysis identified conserved virulence factors, and the isolate successfully propagated in mammalian cells, suggesting its ability to cause diseases in humans. The presence of SFG rickettsia in unfed larvae implies potential dual‐pathogen carriage and reflects a symbiotic relationship similar to that between the mites and O. tsutsugamushi, indicating possibility of its transovarial transmission from female adults. Furthermore, conserved genomic similarity of the novel isolate to known SFG rickettsia suggests potential multiple hosts, including chiggers and ticks. In the natural environment, ticks, chigger mites, and wild animals may carry new isolates, complicating the infection cycle and increasing the transmission risks to humans. This discovery challenges the conventional association of SFG rickettsia with ticks, emphasizing its implications for research and disease control. However, this study was confined to a particular species of chigger mites and geographic area, underscoring the necessity for additional studies to comprehend the ecological dynamics, host interactions, and health implications linked to this newly identified SFG rickettsia. [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]

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]

This study evaluated the use of F-18 fluorodeoxyglucose (FDG) PET/CT imaging to differentiate between scrub typhus and systemic lupus erythematosus (SLE) in patients presenting with lymphadenopathy. We carried out a retrospective analysis of 18 scrub typhus patients and seven SLE patients, using various imaging parameters, including lymph node size, spleen and liver lengths, the distance between the two farthest lesions (Dmax), and assessments of glucose metabolism. On FDG PET images, we measured the maximum standardized uptake value (SUVmax) of the lymph nodes, spleen, and liver and the mean standardized uptake value (SUVmean) of the liver and spleen. The Dmax values of scrub typhus patients were significantly longer than those of SLE patients, indicating that lymphadenopathy is more generalized in the patients with scrub typhus. The SUVmax values for the lymph node, spleen, and liver were also higher in patients with scrub typhus, while the SUVmean of the liver and spleen did not differ between the two groups. This study is the first to compare FDG PET/CT images between these two conditions, suggesting the potential of this imaging modality to provide critical diagnostic distinctions. [ABSTRACT FROM AUTHOR]

Introduction: Scrub typhus or bush typhus or chigger - borne typhus is a leading cause of undifferentiated febrile illness caused by the intracellular gram negative bacteria orientia tsutsugamushi of family rickettsiaceae which was first isolated and identified in 1930 in japan. Bacteria orientia tsutsugamushi of family rickettsiaceae which was first isolated and identified in 1930 in japan. Humans are infected when they are bitten by the mite larvae(chiggers). The available serological methods for diagnosis of scrub typhus were weil felix test, ifa and elisa .in this study we used elisa for detection of igm antibodies, which has a good sensitivity and specitivity. Aim: To determine the seroprevalence of scrub typhus among febrile patients attending to tertiary care hospital using igm elisa. Materials and Methods: This study is prospective observational study was conducted since june 2023 to november 2023(6months period), at tertiary care hospital guntur. total 366 samples were tested for scrub typhus by igm elisa. these samples also testedfor other diseases like malaria, dengue fever, enteric fever, leptospiroses and other fevers which are common cause of fever prevalent in this area. Results - out of 366 samples 41 were detected igm antibodies by elisa, in that, males were 22(53.65%) and females were 19(46.34%). age group mostly involved were below 20 years . Conclusion: Scrub typhus should include in common cause of febrile illness along with other causes which are prevalent in this area, and test for detection and diagnosis of scrub typhus should include in the panel of diagnostic tests for febrile illness. [ABSTRACT FROM AUTHOR]

Background: Fever associated with thrombocytopenia is a common clinical issue in pediatric wards. Literature shows very minimal data on fever associated with thrombocytopenia in children, even though there are some studies on profile of individual diseases like dengue fever, typhoid fever, malaria in children. Aim & Objective: This study was conducted to analyze clinico-etiological profile in preference to infective etiology and outcome of children with febrile thrombocytopenia. This was a prospective observational study conducted in Pediatric Dept, Government Medical College, Anantapur from January 2021 to June 2022. 150 children in the age group of one month to twelve years of age who fulfilled the criteria of fever for 5 days or more with thrombocytopenia were taken into the study and children with known ITP and hematological malignancy, Pseudo thrombocytopenia were excluded. After informed written consent detailed history, clinical examination and necessary laboratory investigation were undertaken. Study parameters were documented in Excel spread sheet and analyzed using SPSS version 16 software. Results: This study demonstrated no gender difference. Analysis of different age group revealed two third study group comprised of children more than 5 years. Comparison of different age group and gender was done which showed in infants, toddlers and preschool children, males were more affected and in school going children females were more affected. Geographic and Seasonal analysis revealed more than 50% children from Anantapur, Hindupur, Kalyandurg and 62% of the children were residing in Rural areas. 85% of study group presented between months of August and November. Clinical features and Physiological status at admission were analyzed for frequency and occurrence in different age groups which revealed altered sensorium, GI bleeds, seizures and oliguria were common in infants. Hepatomegaly was seen in two third children, facial puffiness in half, pallor in one-third. Shock was seen in 26% of children. Shock was frequent in infants. Positive Tourniquet testing was seen in 21% children. Thrombocytopenia was graded as per WHO guidelines, of which 46% hadsevere and 43% had moderate thrombocytopenia. Severe type of thrombocytopenia was the common type associated with bleeding manifestations. Among bleeding manifestations GI bleeds was the commonest followed by petechiae and other bleeds, bleeding manifestations were common among infants, school going children. Bleeding manifestations were common in ALL followed by Dengue fever. Univariate analysis of clinical signs and lab parameters among the bleeding manifestations group and non- bleeding manifestations group was undertaken. Mortality in febrile thrombocytopenia is 3.3%. This was due to Multi-Organ Dysfunction Syndrome. Blood product transfusion was given in 8 patients of which 2 required Platelet Transfusion due to severe Thrombocytopenia, 3 required FFP Transfusion due to Coagulopathy, 3 required Fresh Whole Blood due to Falling Hematocrit. Conclusion: The analysis revealed significant association between bleeding manifestation and positive tourniquet test and low platelet count. Early rise in platelet count (< 3 days) was seen in nonbleeding group compared to bleeding group. In this study Dengue Fever was the commonest etiology followed by Undifferentiated fever, Malaria, Scrub typhus and Enteric Fever. [ABSTRACT FROM AUTHOR]

Simple Summary: Leptotrombidium imphalum (a chigger species) can serve as a transmitting vector of scrub typhus. Based on the field investigation in southwest China from 2001 to 2022, this article presents the first report on the distribution and infestation of L. imphalum on small mammals in the region. A total of 2161 L. imphalum were identified from 218 small mammal hosts that crossed three orders, and the majority of the mites were found on the order Rodentia (rodents). Different host species had different susceptibility to the infestation of L. imphalum, and the shrew gymnure (Neotetracus sinensis) was much more susceptible to the infestation than other host species. Leptotrombidium imphalum exhibited an aggregated distribution among different individuals of its hosts. The positive correlation between the infestation indices for L. imphalum on small mammals and the occurrence of scrub typhus, together with the low host specificity of the mite, indicates the potential risk of the mite. Leptotrombidium imphalum is a species of chigger mites, and it can serve as a transmitting vector of scrub typhus. Southwest China is an important focus of scrub typhus. Based on the field investigation in southwest China from 2001 to 2022, this article presents the first report on the distribution and infestation of L. imphalum on rodents and other sympatric small mammals in the region. A total of 2161 L. imphalum were identified from 218 small mammal hosts in 21 of 114 survey sites. The 17 host species of L. imphalum crossed 13 genera and 5 families in 3 orders (Rodentia, Eulipotyphla, and Scandentia), indicating the low host specificity of the mite. The Asian house rat (Rattus tanezumi) was the dominant host species in the 21 sites where L. imphalum were collected, and 49.38% of mites were found on R. tanezumi. Different small mammals had different susceptibility to the infestation of L. imphalum. The prevalence (PM = 27.66%), infestation mean abundance (MA = 6 mites/per examined host), and mean intensity (MI = 21.69 mites/per infested host) for L. imphalum on the shrew gymnure (Neotetracus sinensis) were much higher than those on other host species (p < 0.05), indicating N. sinensis had a high susceptibility to the infestation of L. imphalum. The infestation indices for L. imphalum on small mammal hosts varied along different altitude and latitude gradients (p < 0.05), indicating the environmental heterogeneity of the mite infestation. Leptotrombidium imphalum exhibited an aggregated distribution among different individuals of its hosts. Besides the low host specificity of L. imphalum, the prevalence of the mite was positively correlated with the occurrence of scrub typhus, indicating the potential risk of the mite. [ABSTRACT FROM AUTHOR]

Background: Acute undifferentiated fever (AUF) remains a significant reason for hospitalization among children, particularly in Southeast Asia. Common causative agents include dengue, scrub typhus, murine typhus, leptospirosis, and enteric fever. This study aims to delineate the clinical and etiological profiles of AUF in children. Materials and Methods: A prospective observational study was conducted over one year in the Department of Pediatrics at a tertiary care hospital in Central India. The study enrolled children with fever lasting less than 21 days and without a specific focus of infection identified through history, physical examination, and routine investigations. Results: Among the 90 children included in the study, the most prevalent cause of undifferentiated fever was typhoid fever (31.1%), followed by malaria (21.1%), dengue fever (18.9%), and urinary tract infections (10%). Other notable causes included acute gastroenteritis (8.9%), pneumonia (5.6%), bronchiolitis (2.2%), hepatitis (1.1%), and pharyngotonsillitis (1.1%). Common clinical symptoms observed were pyrexia (100%), headache (65.6%), rash (47.8%), and abdominal pain (31.1%). Laboratory findings indicated mild anemia in the majority of cases, leukopenia in cases of dengue and malaria, and thrombocytopenia in dengue cases. Conclusion: Non-malarial infections are predominant causes of AUF in children within this region of Central India. Scrub typhus, dengue, and enteric fever were identified as significant contributors. The study underscores the necessity for improved diagnostic facilities to reduce the proportion of undiagnosed fevers, often assumed to be viral in nature. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article in the International Journal of Dermatology provides an update on the Borealpox virus, previously known as Alaskapox, which caused the first mortality in an immunocompromised patient in Alaska. The virus was initially misdiagnosed as a spider bite and was later classified as an Orthopoxvirus. The primary hosts for the Borealpox virus are red-backed voles and squirrels, with cats and dogs potentially acting as intermediate hosts. The article emphasizes the importance of recognizing the clinical characteristics of Borealpox to prevent unnecessary alarms and maintain vigilance, especially in the context of changing epidemiology and global spread potential. [Extracted from the article]

Background: Febrile illnesses that persist despite initial treatment are common clinical challenges in (sub)tropical low-resource settings. Our aim is to review infectious etiologies of "prolonged fevers" (persistent febrile illnesses, PFI) and to quantify relative contributions of selected neglected target diseases with limited diagnostic options, often overlooked, causing inadequate antibiotic prescriptions, or requiring prolonged and potentially toxic treatments. Methods: We performed a systematic review of articles addressing the infectious etiologies of PFI in adults and children in sub-/tropical low- and middle-income countries (LMICs) using the PRISMA guidelines. A list of target diseases, including neglected parasites and zoonotic bacteria (e.g., Leishmania and Brucella), were identified by infectious diseases and tropical medicine specialists and prioritized in the search. Malaria and tuberculosis (TB) were not included as target diseases due to well-established epidemiology and diagnostic options. Four co-investigators independently extracted data from the identified articles while assessing for risk of bias. Results: 196 articles from 52 countries were included, 117 from Africa (33 countries), 71 from Asia (16 countries), and 8 from Central and -South America (3 countries). Target diseases were reported as the cause of PFI in almost half of the articles, most frequently rickettsioses (including scrub typhus), relapsing fever borreliosis (RF-borreliosis), brucellosis, enteric fever, leptospirosis, Q fever and leishmaniasis. Among those, RF-borreliosis was by far the most frequently reported disease in Africa, particularly in Eastern Africa. Rickettsioses (including scrub typhus) were often described in both Africa and Asia. Leishmaniasis, toxoplasmosis and amoebiasis were the most frequent parasitic etiologies. Non-target diseases and non-tropical organisms (Streptococcus pneumoniae, Escherichia coli, and non-typhoidal Salmonella spp) were documented in a fifth of articles. Conclusions: Clinicians faced with PFI in sub-/tropical LMICs should consider a wide differential diagnosis including enteric fever and zoonotic bacterial diseases (e.g., rickettsiosis, RF-borreliosis and brucellosis), or parasite infections (e.g., leishmaniasis) depending on geography and syndromes. In the absence of adequate diagnostic capacity, a trial of antibiotics targeting relevant intra-cellular bacteria, such as doxycycline or azithromycin, may be considered. Author summary: "Prolonged" or "Persistent" Febrile illnesses (PFI) are common challenging diagnostic entities in LMICs. Symptoms and signs can be non-specific and diagnostic tests are often not available, and antibiotics inadequate. This systematic review aimed to investigate important causes of PFI in different geographical regions, as well as to highlight lack of data in these areas to stimulate discussion for future research. We found that zoonotic bacterial and neglected parasitic diseases accounted for substantial proportions of PFI cases, in particular rickettsiosis, borreliosis, brucellosis, leptospirosis, melioidosis, leishmaniasis, toxoplasmosis and amoebiasis. Although data is very limited for many regions, our results suggest that the geographical context can help inform clinicians on the likelihood of different infections in a patient with PFI. [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]

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]

Key Clinical Message: In this case report, we describe the successful management of severe scrub typhus with pneumonia, sepsis, and multiple organ dysfunction in a pregnant woman. Despite initial challenges, the patient responded favorably to fecal microbiota transplantation and oral fecal microbiota capsule therapy. Scrub typhus, caused by Orientia tsutsugamushi, can lead to severe multiorgan dysfunction and carries a mortality rate of up to 70% if not treated properly. In this report, we present the case of a 27‐year‐old pregnant woman at 18 + 6 weeks gestation whose symptoms worsened 15 days after onset and progressed to severe pneumonia with sepsis and multiple organ dysfunction syndrome. After the pathogen was confirmed by next‐generation sequencing analysis of bronchoalveolar‐lavage fluid and blood samples, the patient's treatment was switched to antiinfective chloramphenicol. The patient also underwent uterine evacuation due to a miscarriage. Extracorporeal membrane oxygenation was discontinued once the pulmonary infection significantly improved. Subsequently, the patient had recurrent diarrhea, abdominal distension, and difficulty eating. The antibiotic regimen was adjusted according to the drug sensitivity, but the diarrhea and abdominal distension still did not improve. Following a comprehensive multidisciplinary risk assessment, we initiated fecal microbiota transplantation and oral fecal microbiota capsule therapy. As a result, the patient's condition was effectively managed, and they were gradually discharged. Fecal microbiota transplantation may be a safe and effective treatment for severe pneumonia and shock in pregnant women. This has significant implications for maternal health. However, further clinical cases are required to observe its long‐term effectiveness. [ABSTRACT FROM AUTHOR]

Scrub typhus is an acute febrile disease due to Orientia tsutsugamushi (Ot) infection and can be life-threatening with organ failure, hemorrhage, and fatality. Yet, little is known as to how the host reacts to Ot bacteria at early stages of infection; no reports have addressed the functional roles of type I versus type II interferon (IFN) responses in scrub typhus. In this study, we used comprehensive intradermal (i.d.) inoculation models and two clinically predominant Ot strains (Karp and Gilliam) to uncover early immune events. Karp infection induced sequential expression of Ifnb and Ifng in inflamed skin and draining lymph nodes at days 1 and 3 post-infection. Using double Ifnar1-/-Ifngr1-/- and Stat1-/- mice, we found that deficiency in IFN/STAT1 signaling resulted in lethal infection with profound pathology and skin eschar lesions, which resembled to human scrub typhus. Further analyses demonstrated that deficiency in IFN-γ, but not IFN-I, resulted in impaired NK cell and macrophage activation and uncontrolled bacterial growth and dissemination, leading to metabolic dysregulation, excessive inflammatory cell infiltration, and exacerbated tissue damage. NK cells were found to be the major cellular source of innate IFN-γ, contributing to the initial Ot control in the draining lymph nodes. In vitro studies with dendritic cell cultures revealed a superior antibacterial effect offered by IFN-γ than IFN-β. Comparative in vivo studies with Karp- and Gilliam-infection revealed a crucial role of IFN-γ signaling in protection against progression of eschar lesions and Ot infection lethality. Additionally, our i.d. mouse models of lethal infection with eschar lesions are promising tools for immunological study and vaccine development for scrub typhus. Author summary: Scrub typhus can lead to severe complications and even fatality if not treated properly; however, the early host immune responses to Ot bacterium infection remain unclear. This study focused on the functional roles of IFNs in i.d. inoculation mouse models of scrub typhus. We found that mice lacking IFN receptors were highly susceptible to Ot infection, which resulted in severe pathology and skin eschar lesions that resembled to human scrub typhus. Further investigation revealed that the lack of IFN-γ, but not IFN-I, resulted in dysregulated innate immune responses, leading to uncontrolled bacterial burdens and tissue damage. Using IFN-γ reporter mice and neutralizing antibody treatment, we confirmed that NK cells were the major source of early IFN-γ, and thus contributed to the bacterial control in the draining lymph nodes. Moreover, our comparative studies with two Ot strains revealed bacterium strain- and dose-dependent eschar formation and disease severity. In conclusion, our study highlights the crucial role of IFN-γ signaling in ensuring host protection against Ot infection. Our mouse models resemble skin eschar lesions and lethal infections observed in human disease, offering potential for future immunological studies on scrub typhus. [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 (ST) is endemic in Fukushima, with the largest number of cases reported in Japan from 2009 to 2010. Although ST is highly treatable, its atypical clinical presentation impedes diagnosis, causing delays in treatment. Methods We review the clinical features of ST in adults from 2008 to 2017 at Ohta Nishinouchi General Hospital in Fukushima, Japan. Results Fifty-five cases (serotype Karp 24, Irie/Kawasaki 21, Hirano/Kuroki 10) of ST were confirmed via serology based on elevated immunoglobulin (Ig)M and IgG and polymerase chain reaction positivity of eschar samples. The mean age was 69 years, and 64% were female. The case fatality rate was 1.8% (1/55). Approximately 70% of cases (38/55) were not diagnosed as ST upon the initial clinic visit. Inappropriate use of antibiotics was identified in 22% of cases (12/55). In terms of atypical clinical features, 1 or more of the manifestations, fever, rash, and eschar, was absent in 31% of cases (17/55). Approximately 11% of cases presented without eschar (6/55; Karp 1, Irie/Kawasaki 1, Hirano/Kuroki 4). Moreover, severe complications were observed with shock and disseminated intravascular coagulation in 7% of cases (4/55), Thus, while 53% of cases presented with the typical triad (29/55), unusual complications and atypical features occurred in 40% (22/55). Conclusions Diagnosis of ST becomes clinically challenging in the absence of typical features. In Fukushima, an endemic area of ST, an atypical presentation involving multisystem disease is common. [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]

Objective: Acute encephalitis syndrome (AES) in children results in significant neurocognitive deficits or mortality. It is pertinent to study the AES patterns periodically to identify the changes in the etiological trends and outcomes. Our objective was to find the etiological agents of AES, mode of diagnosis, treatment given, and outcomes. Methods: We reviewed the electronic records of children aged 1 month to 15 years who were admitted with AES in our centre from January 2015 to December 2019. We analyzed the the clinical, laboratory, and radiological profile of these children and adolescents in relation to their outcome. Poor outcome was defined as death, discharge against medical advice with neurological deficits, or Glasgow Outcome Score Extended (GOS-E) d≤ 5 at the time of discharge. Results: Among 250 patients admitted with AES during the study period, a definitive etiological diagnosis was established in 56.4% of children (30.4% viral, 22% bacterial). Scrub typhus (11.2%) and dengue (9%) were the two most common underlying illnesses. Serology helped in clinching the diagnosis in 30% of children. A surge in AES cases in the post-monsoon season was observed in our cohort. Third-generation cephalosporin drugs (85.7%) and acyclovir (77.7%) were the most commonly used empiric antimicrobial drugs. About one-third of children (n = 80) had a poor outcome. GCS ≤ 8 at presentation and requirement for invasive ventilation were found to be significant predictors of poor outcome. Conclusion: A definitive diagnosis was obtained in about half of the children with AES. Viral (30.4%) and rickettsial infections (22%) were the common etiologies identified. Poor outcome was observed in 32 % of patients. [ABSTRACT FROM AUTHOR]

Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID‐associated multisystem inflammatory syndrome (MIS‐C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS‐C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS‐C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL‐1RA, IL‐1β, and TNF compared with MIS‐C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL‐6:IL‐10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL‐6:IL‐10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation. [ABSTRACT FROM AUTHOR]