CNS Manifestations in Orientia tsutsugamushi Disease (Scrub Typhus) in North India

Sood, Anil K.; Chauhan, Lokesh; Gupta, Hemlata

doi:10.1007/s12098-015-2001-2

Cited by 27 publications

(23 citation statements)

References 36 publications

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“…CNS alterations are evident in scrub typhus patients [7,8,9], in a mouse self-limiting model [15], and in our studies herein. However, Orientia antigens in mouse brains seems sparse (Fig 5)[17], often 50-200-fold less in bacterial gene copies than in the lungs [15,17].…”

Section: Resultssupporting

confidence: 65%

“…Disease severity and mortality are associated with increased endothelial and macrophage markers [4]. CNS involvement is common among severe cases, and diverse neurological symptoms, including headache, vomiting, altered sensorium, seizures, have been reported [5,6,7,8,9]. Patients can be categorized into meningitis, encephalopathy, and encephalitis, based on neck stiffness, consciousness level, and cerebrospinal fluid cell count, as well as other pathological evidence of focal neurological deficits [10,11,12].…”

Section: Introductionmentioning

confidence: 99%

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Type 1-skewed neuroinflammation and vascular damage associated with Orientia tsutsugamushi infection in mice

et al. 2017

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BackgroundScrub typhus is a life-threatening disease, due to infection with O. tsutsugamushi, a Gram-negative bacterium that preferentially replicates in endothelial cells and professional phagocytes. Meningoencephalitis has been reported in scrub typhus patients and experimentally-infected animals; however, the neurological manifestation and its underlying mechanisms remain poorly understood. To address this issue, we focused on Orientia tsutsugamushi Karp strain (OtK), and examined host responses in the brain during lethal versus self-healing scrub typhus disease in our newly established murine models.Principle findingsFollowing inoculation with a lethal dose of OtK, mice had a significant increase in brain transcripts related to pathogen-pattern recognition receptors (TLR2, TLR4, TLR9), type-1 responses (IFN-γ, TNF-α, CXCL9, CXCR3), and endothelial stress/damage such as angiopoietins, but a rapid down-regulation of Tie2. Sublethal infection displayed similar trends, implying the development of type 1-skewed proinflammatory responses in infected brains, independent of time and disease outcomes. Focal hemorrhagic lesions and meningitis were evident in both infection groups, but pathological changes were more diffuse and frequent in lethal infection. At 6–10 days of lethal infection, the cortex and cerebellum sections had increased ICAM-1-positive staining in vascular cells, as well as increased detection of CD45+ leukocytes, CD3+ T cells, IBA1+ phagocytes, and GFAP+ astrocytes, but a marked loss of occludin-positive tight junction staining, implying progressive endothelial activation/damage and cellular recruitment in inflamed brains. Orientia were sparse in the brains, but readily detectable within lectin+ vascular and IBA-1+ phagocytic cells. These CNS alterations were consistent with type 1-skewed, IL-13-suppressed responses in lethally-infected mouse lungs.SignificanceThis is the first report of type 1-skewed neuroinflammation and cellular activation, accompanied with vascular activation/damage, during OtK infection in C57BL/6 mice. This study not only enhances our understanding of the pathophysiological mechanisms of scrub typhus, but also correlates the impact of immune and vascular dysfunction on disease pathogenesis.

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Section: Resultssupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Type 1-skewed neuroinflammation and vascular damage associated with Orientia tsutsugamushi infection in mice

et al. 2017

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“…Central nervous system involvement is not uncommon in scrub typhus with non-specific CSF and neuro-radiology findings [ 53 ]. In this study, CSF findings in scrub typhus meningitis mimicked tuberculosis except for ADA levels (two had ADA ≥10 U/L).…”

Section: Discussionmentioning

confidence: 99%

Clinical and paraclinical profile, and predictors of outcome in 90 cases of scrub typhus, Meghalaya, India

et al. 2016

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BackgroundIndia is an integral component of “tsutsugamushi triangle” which depicts a part of the globe endemic to scrub typhus. Owing to frequent outbreaks witnessed in different parts of the country in the recent past, scrub typhus is described as a re-emerging infectious disease in India. The present study aimed to study the clinical and paraclinical profile, complications and predictors of outcome among 90 cases of scrub typhus diagnosed in a hospital of north-eastern India from Sept 2011 to Aug 2012.MethodsA longitudinal study was conducted in a hospital of Meghalaya, India between Sept 2011 and Aug 2012. Diagnosis of scrub typhus was arrived by SD BIOLINE tsutsugamushi (solid phase immunochromatographic assay) rapid diagnostic test for antibodies (IgM, IgG or IgA). Descriptive analyses of age, gender, geographic area, symptoms and signs, treatment, laboratory findings, complications, and outcome were conducted. Relative risk (RR) with 95 % confidence interval (CI) was computed for Multiple Organ Dysfunction Syndrome (MODS) and mortality. Binary logistic regression was applied to the significant correlates (P < 0.05) on univariate analysis to identify the predictors of MODS and mortality in scrub typhus.ResultsAs many as 662 clinically suspected scrub typhus patients were tested and 90 (13.6 %) were diagnosed to have scrub typhus. Out of 90 patients, 52.2 % (n = 47) were males and their mean (SD) age was 36.29 (13.38) years. Fever of <7 days (n = 75, 83.3 %), myalgia (n = 56, 62.2 %), pain abdomen (n = 24, 26.7 %), headache (n = 24, 26.7 %), nausea/vomiting (n = 21, 23.3 %), dry cough (n = 21, 23.3 %), hepatomegaly (n = 24, 26.7 %), splenomegaly (n = 22, 24.4 %), and lymphadenopathy (n = 20, 22.2 %) were the predominant clinical features. Eschar was seen in 10 patients (11.1 %). One third (n = 30) of the patients developed at least one systemic complication. Acute hepatitis (n = 15, 16.7 %), pneumonitis (n = 14, 15.6 %), and acute kidney injury (n = 11, 12.2 %) were the common complications. MODS was seen in 14.4 % (n = 13) and 38.5 % (n = 5) of the patients with MODS died. Overall, case fatality rate was 5.15 % (n = 5). On univariate analysis, platelets <100 000/mm3, serum creatinine >1.5 mg/dl, and transaminase (AST, ALT or both) >500 U/L were associated with MODS (P < 0.001) and mortality (P < 0.05). In addition, serum bilirubin >3 mg/dl was also associated with MODS (P < 0.001). On applying binary logistic regression, serum creatinine >1.5 mg/dl was a predictor of MODS (OR: 76.1, 95 % CI: 4.9–1175.6) and mortality (OR: 18.03, 95 % CI: 1.38–235.1).ConclusionIn this study setting, approximately one-seventh (13.6 %) of the acute undifferentiated febrile illness were due to scrub typhus. Systemic complications were common (33.3 %). Serum creatinine >1.5 mg/dl was a predictor of MODS and mortality.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-016-0186-x) contains supplementary material, which is available to authorized users.

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“…Sometimes acute fulminant myocarditis may lead to cardiogenic shock. 23 Indian literature has reported quite a high rate of central nervous system involvement, 24,25 AKI, requirement of renal replacement therapy, 26 thrombocytopenia, disseminated intravascular coagulation, 15,27 and HLH. 28 We have found a significant association of altered sensorium and reduced urine output with the development of MODS during the course of illness.…”

Section: Discussionmentioning

confidence: 99%

Predictors of Severity of Scrub Typhus in Children Requiring Pediatric Intensive Care Admission

Khemka

Sarkar

Basu

et al. 2021

J Pediatr Intensive Care

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Objective of our study was to determine the clinical characteristics and laboratory profile of scrub typhus patients requiring pediatric intensive care admission and to find out risk factors for the severity of illness. This was a cross-sectional observational study conducted on 1-month to 12-year-old children admitted with scrub typhus in a tertiary care pediatric intensive care unit (PICU). Relevant demographic, clinical, laboratory, treatment, and outcome-related data were documented. The severity of the disease was measured in the form of multiple organ dysfunction syndrome (MODS). With further correlation, and univariate and multivariate analyses, factors associated with severe disease were identified. During the study period, out of 586 PICU admission, 62 patients (10.6%) were diagnosed with scrub typhus. The mean age was 63.85 ± 52.78 months, where infants constituted 32.3% of the total population. Fever was present in 100% of the cases. Common indications of PICU admission were: respiratory distress 42 (67.7%), altered sensorium 41 (66.1%), convulsion 37 (59.7%), and shock 31 (50%). Total number of patients with MODS was 40 (64.5%). The case fatality rate was 8%. On multivariate analysis, infant age group (p = 0.02), altered sensorium (p = 0.001), reduced urine output (p = 0.02), thrombocytopenia (p = 0.001), raised C-reactive protein (p = 0.004), hyponatremia (p = 0.005), hypoalbuminemia (p = 0.01), deranged international normalized ratio (p = 0.02), and hyperferritinemia (p = 0.02) came out to be independent factors in predictability for development of MODS. Multiorgan dysfunction is a life-threatening manifestation of scrub typus in children, which necessitates PICU admission. Infant age group, presence of altered sensorium, reduced urine output, thrombocytopenia, elevated inflammatory markers, coagulopathy, hypoalbuminemia, and hyponatremia predict risk for MODS.

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CNS Manifestations in Orientia tsutsugamushi Disease (Scrub Typhus) in North India

Cited by 27 publications

References 36 publications

Type 1-skewed neuroinflammation and vascular damage associated with Orientia tsutsugamushi infection in mice

Type 1-skewed neuroinflammation and vascular damage associated with Orientia tsutsugamushi infection in mice

Clinical and paraclinical profile, and predictors of outcome in 90 cases of scrub typhus, Meghalaya, India

Predictors of Severity of Scrub Typhus in Children Requiring Pediatric Intensive Care Admission

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