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Association of Scrub Typhus in Children with Acute Encephalitis Syndrome and Meningoencephalitis, Southern India.

ABSTRACT: Scrub typhus is an established cause of acute encephalitis syndrome (AES) in northern states of India. We systematically investigated 376 children with AES in southern India, using a stepwise diagnostic strategy for the causative agent of scrub typhus, Orientia tsutsugamushi, including IgM and PCR testing of blood and cerebrospinal fluid (CSF) to grade its association with AES. We diagnosed scrub typhus in 87 (23%) children; of those, association with AES was confirmed in 16 (18%) cases, probable in 55 (63%), and possible in 16 (18%). IgM detection in CSF had a sensitivity of 93% and specificity of 82% compared with PCR. Our findings suggest scrub typhus as an emerging common treatable cause of AES in children in southern India and highlight the importance of routine testing for scrub typhus in diagnostic algorithms. Our results also suggest the potential promise of IgM screening of CSF for diagnosis of AES resulting from scrub typhus.

SUBMITTER: Damodar T

PROVIDER: S-EPMC10045701 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Association of Scrub Typhus in Children with Acute Encephalitis Syndrome and Meningoencephalitis, Southern India.

Damodar Tina T Singh Bhagteshwar B Prabhu Namratha N Marate Srilatha S Gowda Vykuntaraju K VK Lalitha A V AV Dsouza Fulton Sebastian FS Sajjan Sushma Veeranna SV Kariyappa Mallesh M Kinhal Uddhava V UV Prathyusha P V PV Desai Anita A Thennarasu Kandavel K Solomon Tom T Ravi Vasanthapuram V Yadav Ravi R

Emerging infectious diseases 20230401 4

Scrub typhus is an established cause of acute encephalitis syndrome (AES) in northern states of India. We systematically investigated 376 children with AES in southern India, using a stepwise diagnostic strategy for the causative agent of scrub typhus, Orientia tsutsugamushi, including IgM and PCR testing of blood and cerebrospinal fluid (CSF) to grade its association with AES. We diagnosed scrub typhus in 87 (23%) children; of those, association with AES was confirmed in 16 (18%) cases, probabl ...[more]

PMID: 36957990

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Project description: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.

Project description:BackgroundInfection-related acute kidney injury (AKI) is an important preventable cause of morbidity and mortality in the tropical region. The prevalence and outcome of kidney involvement, especially AKI, in scrub typhus is not known. We investigated all patients with undiagnosed fever and multisystem involvement for scrub typhus and present the pattern of renal involvement seen.MethodsFrom September 2011 to November 2012, blood samples of all the patients with unexplained acute febrile illness and/or varying organ involvement were evaluated for evidence of scrub typhus. A confirmed case of scrub typhus was defined as one with detectable Orientia tsutsugamushi deoxyribonucleic acid (DNA) in patient's blood sample by nested polymerase chain reaction (PCR) targeting the gene encoding 56-kDa antigen and without any alternative etiological diagnosis. Renal involvement was defined by demonstration of abnormal urinalysis and/or reduced glomerular filtration rate. AKI was defined as per Kidney Disease: Improving Global Outcomes (KDIGO) definition.ResultsOut of 201 patients tested during this period, 49 were positive by nested PCR for scrub typhus. Mean age of study population was 34.1±14.4 (range 11-65) years. Majority were males and a seasonal trend was evident with most cases following the rainy season. Overall, renal abnormalities were seen in 82% patients, 53% of patients had AKI (stage 1, 2 and 3 in 10%, 8% and 35%, respectively). The urinalysis was abnormal in 61%, with dipstick positive albuminuria (55%) and microscopic hematuria (16%) being most common. Acute respiratory distress syndrome (ARDS) and shock were seen in 57% and 16% of patients, respectively. Hyperbilirubinemia was associated with AKI (p = 0.013). A total of 8 patients (including three with dialysis dependent AKI) expired whereas rest all made uneventful recovery. Jaundice, oliguria, ARDS and AKI were associated with mortality. However, after multivariate analysis, only oliguric AKI remained a significant predictor of mortality (p = 0.002).ConclusionsScrub typhus was diagnosed in 24% of patients presenting with unexplained febrile illness according to a strict case definition not previously used in this region. Renal abnormalities were seen in almost 82% of all patients with evidence of AKI in 53%. Our finding is contrary to current perception that scrub typhus rarely causes renal dysfunction. We suggest that all patients with unexplained febrile illness be investigated for scrub typhus and AKI looked for in scrub typhus patients.

Project description:BackgroundScrub typhus, a vector-borne zoonotic infection caused by the bacteria Orientia tsutsugamushi, is one of the most common and clinically important rickettsial infections worldwide. An estimated one million cases occur annually with a high case fatality rate. Although scrub typhus is a major public health threat in India, the burden and distribution remains unclear. We aimed to estimate the burden of scrub typhus in India.MethodologyWe performed a systematic review of published literature on scrub typhus from India to extract information on epidemiology, morbidity, and mortality. Important databases were searched using keywords and appropriate combinations. We identified observational, interventional, and population-based studies and extracted the data to evaluate the number of cases diagnosed using serology or PCR and the number of deaths due to scrub typhus. We conducted a systematic narrative synthesis to summarize included studies.Principal findingsIn the last decade, there were 18,781 confirmed scrub typhus cases reported in 138 hospital-based studies and two community-based studies. IgM ELISA was used in 122 studies to confirm the cases in majority (89%). The proportion of scrub typhus among acute undifferentiated febrile illness (AUFI) studies was 25.3%, and community seroprevalence was 34.2%. Ninety studies had data published on multiple organ involvement out of which 17.4% of cases had multiple organ dysfunction syndromes, 20.4% patients required ICU admission, and 19.1% needed ventilation. The overall case-fatality rate was 6.3%, and the mortality among those with multi-organ dysfunction syndrome was as high as 38.9%.Conclusion/significanceScrub typhus, a common acute febrile illness in India causing severe morbidity, accounts for a large number of deaths. The burden of the disease has been underappreciated. Early diagnosis and prompt treatment can significantly reduce complications and mortality. Establishing good surveillance and instituting appropriate control measures are urgently needed.

Dataset Information

Association of Scrub Typhus in Children with Acute Encephalitis Syndrome and Meningoencephalitis, Southern India.

Publications

Association of Scrub Typhus in Children with Acute Encephalitis Syndrome and Meningoencephalitis, Southern India.

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