Scrub Typhus Patients Research Articles

Scrub typhus-leptospirosis co-infection in India: a systematic review and meta-analysis.

Scrub typhus and leptospirosis are re-emerging zoonotic infections with significant morbidity and mortality rates in India. Overlapping aetiological and epidemiological patterns indicate a high possibility of their co-infection in India, which can be a diagnostic challenge due to non-specific clinical features. A systematic search of the PubMed/MEDLINE, Scopus and Embase databases was conducted to identify relevant studies published through 31 August 2023. Studies reporting co-infection of scrub typhus and leptospirosis among the Indian population were included. Data extraction, quality assessment and statistical analysis were performed in accordance with established guidelines. Six studies met the inclusion criteria, comprising a total of 58 co-infection cases. Pooled prevalence of scrub typhus-leptospirosis co-infection among acute undifferentiated febrile illness patients was 3.7% (95% confidence interval [CI] 0.00 to 0.126). Among scrub typhus patients, the prevalence of co-infection with leptospirosis was 13.7% (95% CI 0.027 to 0.304). Significant heterogeneity was observed among the included studies, highlighting the need for cautious interpretation of prevalence estimates. This meta-analysis underscores the clinical importance of scrub typhus-leptospirosis co-infection in India and emphasizes the need for enhanced clinical awareness, improved diagnostic strategies and targeted research efforts to address this emerging infectious disease threat.

Risk factors of thromboembolic events in patients with scrub typhus.

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. 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. 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). 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.

Isolation of Orientia tsutsugamushi in Culture from Vellore, South India.

Background: Orientia tsutsugamushi, causative agent of scrub typhus is an obligate intracellular parasite. We present information on isolation of this pathogen at a tertiary care centre in Vellore, Southern India. Materials & Methods: PBMCs (peripheral blood mononuclear cells) collected from suspected scrub typhus patients were inoculated into Vero and L929 cell lines and incubated at 37°C with 5% CO2 for 30 days. They were examined for presence of Orientia tsutsugamushi on 10, 15, 20 days post-inoculation and everyday thereafter for a maximum of 30 days post inoculation. The scrapings were subjected to Giemsa staining, IFA, 47kDa qPCR and transmission electron microscopy (TEM). The isolates were passaged 3-4 times to ensure viability and then stored in DMEM with 10% FBS (-80). Genotyping of the isolates was performed by amplifying a 650 bp segment of the TSA 56 (type specific antigen 56) gene. Results: Amongst the 50 samples inoculated, three were culture positive as confirmed by 47 kDa qPCR on 24th day post inoculation. This was further confirmed by Giemsa, IFA staining and TEM. The 650bp amplicons showed 99.5 to 100% homology with Orientia tsutsugamushi MW604716, MH003839, MW604718, MW604717, MH922787 and MH003838 strains. Phylogenetic analysis revealed that 2 isolates belong to TA763 genotype and one belongs to Gilliam genotype. Conclusion: Orientia tsutsugamushi has been isolated for the first time at Vellore, South India from PBMCs. Complete genomic analysis will give more information.

C-C Motif Ligand 7 (CCL7) and C-C Motif Chemokine Receptor 3 (CCR3) dysregulation in patients with scrub typhus and association with mortality.

Scrub typhus, caused by Orientia tsutsugamushi involves infiltration of a mixture of perivascular lymphocytes and macrophages into affected organs. We investigated if this is characterized by chemokine dysregulation. mRNA expression of chemokines and receptors were screened in whole blood by cDNA microarray in a subgroup of patients and controls. Regulated transcripts were analyzed in plasma by enzyme immunoassays (chemokines) and in whole blood by qPCR (receptors) from scrub typhus patients (n=129), patients with similar febrile illness without Orentia tsutsugamushi infection (n=31) and healthy controls (n=31). (i) cDNA microarray identified dysregulation of the chemokines CCL18 and CCL23 and CCR3 receptor, in severe scrub typhus. (ii) Plasma CCL7, a ligand for CCR3, CCL18 and CCL23 were higher in scrub typhus patients, with a decline during follow-up. (iii) Conversely, mRNA levels of CCR3 and CCR8, the receptor for CCL18, were decreased in whole blood at hospital admission followed by an increase during follow-up. (iv) CCL7 was independently associated with disease severity. (v) Admission CCL7 levels were associated with short-time mortality. Our findings suggest CCL7 could represent a hitherto unknown pathogenic mediator in Orentia tsutsugamushi infection contributing to local and systemic inflammation.

Estimating the Seroincidence of Scrub Typhus using Antibody Dynamics after Infection.

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.

Comparative analysis of F-18 FDG PET/CT images between scrub typhus and systemic lupus erythematosus

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.

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

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

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

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

Identifying the Probable Etiology of Acute Undifferentiated Fever through Inflammatory Markers.

Acute undifferentiated fever (AUF) is defined as any febrile illness with a duration of ≤14 days without evidence of localized infection. Most outpatient services and a significant inpatient load in India are contributed by AUF. COVID-19 has recently added to the existing list of common etiologies of AUF. While the rapid diagnostic test (RDT) kits, which are widely used for the detection of common etiologies of AUF, are unreliable, the rise of various inflammatory markers may help identify the probable etiology. This not only results in better diagnosis but also prepares the physician for close monitoring and pooling of resources. To identify the probable etiology of AUF through inflammatory markers. To understand the clinical and biochemical parameters as possible predictors of adverse outcomes in AUF. This was a prospective observational study carried out in the Department of Medicine in a tertiary care hospital. The total duration of the study was 1 year. A total of 400 AUF patients [both outpatient department (OPD) and inpatient department (IPD)] fulfilling the eligibility criteria were taken up for the study after consent. Various inflammatory markers, namely erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer, ferritin, and procalcitonin levels along with basic blood and biochemical tests were measured in all qualifying patients at their first visit. The level of rise of all the measured inflammatory markers was analyzed for clues toward identifying the etiology. Also, the possible predictors of adverse outcomes, as defined in the study, were analyzed. Outcome variables are described as mean ± standard deviation. All statistical calculations were done using computer programs Microsoft Excel 2007 (Microsoft Corporation, New York, United States of America) and SPSS (Statistical Product and Service Solutions; SPSS Inc., United States of America) version 21. The common etiologies in our study contributing to AUF were dengue (31.5%), COVID-19 (18.5%), enteric fever (12.7%), scrub typhus (9.0%), and malaria (6.0%). In 76 cases (19%), the fever was undiagnosed. Enteric fever had highly elevated CRP (>30 mg/L) and moderately elevated D-dimer, ferritin, and procalcitonin. Both nonsevere dengue and COVID-19 had highly elevated D-dimer (>750 ng/mL), but in nonsevere dengue, CRP, ferritin, and procalcitonin were only mildly elevated, whereas in COVID-19, CRP and ferritin were moderately elevated with mildly elevated procalcitonin. Scrub typhus had highly elevated CRP and ferritin [more than four times the upper limit of normal (ULN)], but D-dimer and procalcitonin were only mildly elevated. The mean serum procalcitonin level in enteric fever is significantly higher than the other etiologies of AUF. Our study was correctly able to identify 90.8% of nonsevere dengue, 87.8% of typhoid, 83.6% of COVID-19, and 91.4% of scrub typhus patients based on the inflammatory markers level. Obesity, diabetes (both types 1 and 2), hypertension, coronary artery disease (CAD), malignancy, chronic kidney disease (CKD), and chronic lung disease were significantly associated with adverse outcomes. A significant delay in visiting the hospital after the onset of fever was found in all etiologies of AUF, which had adverse outcomes. Our study is one of the few studies comparing the rise in the level of various inflammatory markers among the common etiologies of AUF. The novelty of the study is that it aids in identifying the probable etiology of AUF with good confidence through the levels of inflammatory markers. Also, our study highlights the high-risk factors associated with adverse outcomes in AUF.

Prominent early adulthood hyperferritinemia in scrub typhus

Background: Scrub typhus is an acute infectious disease, caused by Orientia tsutsugamushi. It is endemic to a geographically distinct region of Japan, Taiwan, China, and South Korea, known as the tsutsugamushi triangle, as well as in Nepal, Pakistan, and Papua New Guinea. In India, the incidence of this disease varies from 4-46% with high morbidity and mortality. Methods: In this cross-sectional study at a tertiary care hospital in Kolkata, India we analysed ferritin blood levels along with different demographic and laboratory test parameters of 60 suspected scrub typhus patients who were also scrub typhus IgM antibody positive during a one-year study period. Results: It was found that serum ferritin levels were unusually high in 21-40 years age group patients along with mildly increased urea and creatinine levels. Other important findings were below 40 years of age males were mostly affected, but above 40 years of age, females were generally affected. Haemoglobin and platelet levels were normal in all age groups. Although WBC count and neutrophils were normal in the 21-40 years age group, in other age groups increased levels were observed. CRP, SGPT, and SGOT levels were uniformly high above 20 years of age. Electrolytes were mildly decreased. Conclusions: It appears that oxidative stress-induced acute kidney injury may be an important reason for the rising ferritin levels in the 21-40 years age group. These important findings may be helpful to clinicians in management of these patients.

IJCM_309A: Epidemiological Trends, Clinical Features, and Outcomes in Scrub typhus patients admitted to a tertiary care hospital in Odisha

Background: Scrub typhus is an emerging public health threat in South-Asian countries; with the growing number of cases in India, an understanding of local patterns of disease and factors that place individuals at risk is pivotal to future preventive measures. Objective: To analyze the epidemiological features- annual number of cases, age distribution, sex distribution, and seasonal distribution over the four years. To find out the clinical profile, laboratory features and outcomes of cases of scrub typhus, and to identify the predictors of disease severity. Methodology: A comprehensive retrospective review of scrub typhus cases reported over a 4-year period (2019-2023) was done, with a monthly trend of patients admitted. Data was collected from the case records of patients for demographic characteristics, clinical features, treatment, and outcomes, length of stay (LOS), complications, and mortality. Data was presented in frequencies and proportions, odds ratio (OR) was calculated and a p-value of Results: A total of 886 cases were reported over the four-years. There was a declining epidemiological trend in 2020-21 and then an increasing one. Scrub typhus cases exhibited seasonality, with a peak incidence during winter season. Males were more commonly affected (58.01%), and the age group most susceptible was 19-64 years (52.22%), followed by one-month to 18years (32.22%). Clinical presentations typically included fever (96%), eschar formation (8%) and rash (8%). Complications like pneumonia (13.88%) and AKI (11.73%), were observed in a significant proportion of cases. Mortality was reported in 4.40% of cases. Altered sensorium, deranged LFT, hypotension requiring ionotropic support, requirement of ventilatory support predicted poor outcome. Conclusion: Scrub typhus was seen to cause a multi-system infection among the studied population, causing significant morbidity and mortality. The conditions found associated with poor outcome and mortality can be used as risk factor predictors and help patient management.

Study of Clinical and Demographic Profile of Scrub Typhus Patients Admitted to a Tertiary Care Hospital in Central India

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.

Canonical notch activation in patients with scrub typhus: association with organ dysfunction and poor outcome

PurposeThe 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.MethodsPlasma 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.ResultsOur 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.ConclusionOur 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.

Evaluation of serological tests in the diagnosis of scrub typhus

Scrub typhus is a leading cause of acute undifferentiated febrile illness in India. Overlapping clinical presentation and very low incidence of characteristic eschar makes serology the main stay of diagnosis. IgM ELISA is the most common test performed in tertiary care centres along with rapid diagnostic tests (RDT) and Weil Felix with varying sensitivity and specificityThe present study was conducted to compare the RDT’s and Weil Felix with IgM ELISA and analyse the demographic and clinical profile of scrub positive patientsSerum samples from clinically suspected scrub typhus patients admitted in a tertiary care hospital were tested by Weil Felix, RDT and IgM ELISA. Scrub typhus was confirmed in 38 of the 100 clinically suspected patients by IgM ELISA. Fever was the most common presenting symptom with significant proportion of patients being exposed to vegetation (p=0.0001).Sensitivity of Weil Felix and RDT was 42.1% and 84.2% respectively. Acute Kidney injury was the most common complication and mortality rate was 7.9%.Weil Felix is not a reliable test for scrub typhus diagnosis due to low sensitivity. Results of positive RDT’s can used for early initiation of specific treatment and IgM ELISA can be used as a confirmatory test in highly suspected cases.

Association of scrub typhus with the risk of venous thromboembolism and long-term mortality: a population-based cohort study.

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. 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. 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). 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.

Clinical and investigative profile of scrub typhus patients at a tertiary care center in Southern West Bengal, India

Background: Scrub typhus, caused by Orientia tsutsugamushi, is an acute febrile illness with symptoms such as fever, chills, and organ failure. The similar clinical presentation in other common diseases such as malaria, dengue fever, and typhoid fever creates difficulty and delay in the clinical diagnosis of scrub typhus. This delay may increase the risk of scrub typhus complications. In India, it is a public health issue with a paucity of data. Aims and Objectives: This study aims to evaluate the clinical characteristics, outcomes, and prognostic factors of patients with scrub typhus. Materials and Methods: This institutional-based observational, cross-sectional study was conducted among consecutively selected 154 adult patients suffering from scrub typhus at a Medical College Hospital situated in the southern part of West Bengal, India. All data were collected according to a pre-designed proforma. At the end of the study, results were analyzed statistically. Results: Younger, females, and homemakers are more susceptible to scrub typhus, mostly in the post-monsoon season from July to November. The incidence of scrub typhus complications is high in the southern part of West Bengal. The case fatality rate of scrub typhus is 6.5%. Male sex, pre-hospitalization duration of illness more than 7 days, presence of diabetes mellitus, serum creatinine (Scr) more than 1.5 mg/dL, serum bilirubin more than 3 mg/dL, systolic blood pressure below 90 mmHg, altered sensorium, and acute respiratory distress syndrome were associated with poor prognosis. Conclusion: A high degree of clinical suspicion is required for the early diagnosis of scrub typhus and the factors associated with poor prognosis must be considered to reduce morbidity and mortality.

CagA-positive Helicobacter pylori may promote and aggravate scrub typhus.

Helicobacter pylori (H. pylori) infection may alter the host's resistance to tsutsugamushi disease pathogens through the Th1 immune response, leading to potential synergistic pathogenic effects. A total of 117 scrub typhus cases at Beihai People's Hospital and affiliated hospitals of Youjiang University for Nationalities and Medical Sciences were studied from January to December 2022, alongside 130 healthy individuals forming the control group. All participants underwent serum H. pylori antibody testing. The prevalence of H. pylori infection was significantly higher among scrub typhus patients (89.7%) compared to healthy individuals (54.6%) (p < 0.05). Moreover, type I H. pylori infection was notably more prevalent in scrub typhus cases (67.5%) compared to healthy individuals (30%) (p < 0.05). Multifactorial analysis demonstrated type I H. pylori infection as an independent risk factor for scrub typhus (adjusted odds ratio: 2.407, 95% confidence interval: 1.249-4.64, p = 0.009). Among scrub typhus patients with multiple organ damage, the prevalence of type I H. pylori infection was significantly higher (50.6%) than type II H. pylori infection (15.4%) (χ2 = 4.735, p = 0.030). These results highlight a higher incidence of H. pylori infection in scrub typhus patients compared to the healthy population. Additionally, type I H. pylori strain emerged as an independent risk factor for scrub typhus development. Moreover, individuals infected with type I H. pylori are more susceptible to multiple organ damage. These findings suggest a potential role of H. pylori carrying the CagA gene in promoting and exacerbating scrub typhus.

Hemophagocytic lymphohistiocytosis-a rare life threatening association with scrub typhus: case report

Scrub typhus is an important cause of acute febrile illness and one of the re-emerging infectious diseases in India particularly in southern Rajasthan. Hemophagocytic lympho-histiocytosis (HLH) results from an uncontrolled and ineffective hyperinflammatory response to a variety of triggers. HLH is further subdivided into primary and secondary type. We present a case of Scrub typhus which presented with multiple organ dysfunction syndrome (MODS) and secondary HLH which is a rare entity. A 9-month-old male child presented with high grade fever with encephalopathy. Examination showed hepatosplenomegaly, cervical Lymph adenopathy with eschar mark visible on abdomen. Scrub typhus was suspected on clinical grounds and further investigations were done. Serological diagnosis was strongly positive for scrub typhus. Initially, child did not respond to doxycycline, so further investigations were done to rule out HLH which fits into criteria of secondary HLH as per the revised HLH 2004 protocol. In view of secondary HLH and MODS methylprednisolone was added to treatment. Child responded to steroids and there was complete recovery. Scrub typhus patient with progressive MODS, in spite of appropriate antimicrobial therapy should raise the suspicion of secondary HLH which is rare but life-threatening condition and steroids plays an important role in the management of this condition.

Procalcitonin Levels for Prognosis of Scrub Typhus Patients: A Retrospective Observational Analysis from a Tertiary Care Centre in Northern India

Introduction: Scrub typhus is a major cause of acute febrile illness in India. It presents with various clinical features that vary from fever to multiorgan dysfunction. Similar symptoms and presentations cause difficulty in diagnosis. Therefore, it is important to have early and prompt diagnosis with better prognostic markers to decrease morbidity and mortality. Aim: To determine the prognosis of scrub typhus patients based on the Procalcitonin (PCT) levels. Materials and Methods: This retrospective observational study was conducted in the Microbiology Department of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Uttar Pradesh, India, from January 2022 to January 2023. A total of 120 patients admitted to the hospital, who tested positive for Scrub typhus IgM by ELISA during this period and had a negative blood culture, were included in this study. Data analysis was conducted from February 2023 to April 2023. PCT levels of all these patients at the time of admission were recorded. The demographic information, laboratory parameters, and treatment regimen of these patients were also compiled. Statistical analysis was performed, and p-value was used to determine statistical significance. Results: The majority of the patients belonged to the age group of 21-40 years. Among these, elevated PCT values (ranging from 0.05-89.4 ng/mL) were observed in 112 (93.33%) patients. Twelve (10%) patients died during the study period, and all of them had elevated PCT levels. Among these, six developed septic shock with Multiple Organ Dysfunction Syndrome (MODS). Increased leukocyte values, elevated liver enzymes such as Aspartate Aminotransferase (SGOT/AST) and Alanine Transferase (SGPT/ALT), abnormal coagulation profile, and abnormal renal profile with elevated urea and uric acid levels were found to be significantly associated with scrub typhus patients with elevated PCT values. Conclusion: There is a need to address the role of prognostic markers in the management of scrub typhus patients. This may lead to breakthroughs in the field of diagnostic research and help improve the prognosis of these patients.

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

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