Diagnostic markers of acute encephalitis syndrome and COVID-associated multisystem inflammatory syndrome in children from Southern India.

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-1ß, 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.

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

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.

Guillain-Barre syndrome following scrub typhus: a case report and literature review.

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

Acute ischemic stroke in Tsutsugamushi: understanding the underlying mechanisms and risk factors.

BACKGROUND: Tsutsugamushi (scrub typhus) is an acute infectious febrile disease common in the Asia-Pacific region. Common symptoms of tsutsugamushi include lymphadenopathy, fever, and myalgia, and it rarely causes acute ischemic stroke (AIS). However, we hypothesized that tsutsugamushi infection could trigger AIS. METHOD: We retrospectively examined patients diagnosed with AIS within 2 weeks of tsutsugamushi diagnosis at three hospitals over a 15-year period. We categorized patients who developed AIS while being treated for tsutsugamushi as the case group and those (of similar age and sex) who did not develop AIS as the control group. The case and control groups consisted of 22 and 66 participants, respectively. When a scattered pattern was observed or lesions were found in two or more vascular territories on diffusion-weighted imaging, the pattern was defined as embolic. Other patterns were defined as nonembolic. RESULTS: Among the 19 patients, excluding three with transient ischemic stroke, 15 (78.9%) showed an embolic pattern. Although fever was common in the control group, it was less common in the case group. A higher D-dimer level at the time of hospitalization was associated with the development of AIS in patients with tsutsugamushi. CONCLUSIONS: AIS in patients with tsutsugamushi showed an embolic rather than a non-embolic pattern on brain magnetic resonance imaging. It was more likely to occur in patients with risk factors for stroke. Tsutsugamushi patients with AIS were likely to have no fever or high D-dimer levels. We hypothesized that D-dimers play an important role in the pathophysiology, where tsutsugamushi infection increases the likelihood of AIS.

Clinical and laboratory findings in scrub typhus associated Guillain-Barré syndrome in South Korea.

BACKGROUND AND AIMS: Scrub typhus is an endemic disease in the fall season that occurs in a limited number of places known as the Tsutsugamushi Triangle. Peripheral neuropathy is a common complication of scrub typhus. Herein, we encountered several patients with ascending paralysis after scrub typhus infection, who were diagnosed with Guillain-Barré syndrome (GBS). We aimed to investigate the clinical and laboratory characteristics of patients who developed GBS after scrub typhus. METHODS: Patients were retrospectively recruited from six nationwide tertiary centers in South Korea from January 2017 to December 2021. Patients who had been clinically diagnosed with GBS and confirmed to have scrub typhus via laboratory examination and/or the presence of an eschar before the onset of acute limb paralysis were included. The GBS-associated clinical and electrophysiological characteristics, outcomes, and scrub typhus-associated features were collected. RESULTS: Of the seven enrolled patients, six were female and one was male. The median time from scrub typhus infection to the onset of limb weakness was 6 (range: 2-14) days. All patients had eschar on their bodies. Four patients (57.1%) were admitted to the intensive care unit and received artificial ventilation for respiratory distress. At 6 months, the median GBS disability score was 2 (range, 1-4) points. INTERPRETATION: Patients with scrub typhus-associated GBS have a severe clinical presentation and require intensive treatment with additional immunotherapies. Therefore, GBS should be included in the differential diagnosis when peripheral neuropathies develop during scrub typhus treatment. Notably, scrub typhus is associated to GBS.

Scrub typhus meningoencephalitis in children: an experience from Eastern India.

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

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

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.

A case of pulmonary tuberculosis patient complicated with hemorrhagic fever with renal syndrome and scrub typhus in Yunnan, China: a case report.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) caused by Orthohantavirus (OHV) and scrub typhus (ST) caused by Orientia tsutsugamushi (OT) are two infectious diseases prevalent in southwest China. Rodents are the natural host and the main source of the two diseases. OT infection to humans is usually resulted from bite of an infective chigger mite on rodents, and OHV is transmitted through contact or inhalation of aerosols and secretions from infected rodent. The use of antibiotics and hormones is crucial for infectious diseases, although the clinical manifestations are not obvious and a definitive diagnosis becomes more difficult in the presence of these drugs. Clinically, fever is the first symptom of these two diseases, and most of them are accompanied by common symptoms such as chills and headaches. The clinical symptoms of these two diseases are very similar and therefore it is not easy to make a differential diagnosis. CASE PRESENTATION: In this case, a 44-year-old male famer with pulmonary tuberculosis and a history of working in coal transportation was admitted to the hospital because of respiratory symptoms accompanied by fever, headache, and skin rashes on his body. Biochemical and urinalysis revealed the hepatic and renal injury. The subsequent molecular testing confirmed he suffered from HFRS and scrub typhus simultaneously that the serological and clinical diagnosis could not identify the cause of infection before. Such case has not been reported in Yunnan Province before. CONCLUSION: The clinical diagnosis should be combined with serological and nucleic acid testing approaches for differential diagnosis in areas where HFRS and ST are endemic.

Detection of co-infection with Orientia tsutsugamushand and hemorrhagic fever with renal syndrome by next-generation sequencing.

Purpose: The co-infection with Orientia tsutsugamushand and hemorrhagic fever with renal syndrome is rare. There are many similarities in early clinical practice between the two diseases, and sometimes it is easy to misdiagnose, especially when co-infection occurs.Methods: We describe a patient who presented with fever and headache after bitten by an insect and whose physical examination showed conjunctival hyperemia, eschar and petechiae in tongue and the soft palate. To lead to a diagnosis, the serum antibody of Hantaan virus, Weil-Felix test and  next-generation sequencing of cerebrospinal fluid was performed.Results: The Weil-Felix test was negative on the 15th day after the onset of the disease and a repeated Weil-Felix test on the 21st day showed a titer of 1:160 and the IgM against Hantaan virus was positive. The number of sequence reads identified corresponding to O. tsutsugamushi was 239 with a genomic coverage of 0.9178%. This patient was diagnosed with intracranial infection with Orientia tsutsugamushi and co-infection with epidemic hemorrhagic fever. The symptoms in our patient quickly decreased after the administration of tetracycline.Conclusion: Next-generation sequencing is helpful for the early diagnosis of scrub typhus, especially when the Weil-Felix test is negative. Clinicians need to be reminded to screen for common pathogens that may be co-infected, such as epidemic hemorrhagic fever.

Scrub typus fulminating as liver failure: A rare report.

Scrub typhus is almost an endemic tropical mite-borne, zoonotic illness often cognate with the bacterium Orientia tsutsugamushi. After a typical incubation period of a fortnight, non-specific symptoms including fever, headache, and a specific skin 'eschar' is customary. If untreated after a symptomatic week, scrub typus may precipitate end-organ involvements spiraling into vivid complications. Nevertheless, crub typhus tends to display mild transaminitis, frank liver failure is hardly common in clinical practice. An instance of scrub typus triggering fulminant hepatic failure (FHF) in a middle-aged female is being reported here.

Coagulation Abnormalities in Severe Scrub Typhus and Their Association with Complications.

AIM: To describe coagulation abnormalities and their association with complications in patients with severe scrub typhus. MATERIALS AND METHODS: A cohort study was conducted among all patients of severe scrub typhus [immunoglobulin M (IgM) positive] who reported to this facility from 1st August 2019 to 31st July 2020 and met our inclusion criteria. We estimated the incidence of severe thrombocytopenia (<50,000/µL) and overt disseminated intravascular coagulation (DIC) (DIC score of ≥5). We determined the association [risk (RR) ratios] of these abnormalities with complications of scrub typhus, namely-septic shock, multiple organ dysfunction syndrome (MODS), and septic shock with MODS. RESULTS: In total, 71 patients were studied with a mean age of 50 ± 15.5 years, of which 45 (63.4%) were females. On presentation, fever 70 (98.5%), myalgias 22 (31.0%), loose stools 13(18.3%), cough, vomiting, headache 11 (15.5%), altered sensorium 10(14.1%), and pain abdomen 9 (12.7%) were main symptoms. On examination, hypotension 31 (43.7%), eschar 25 (35.2%), icterus 17 (23.9%), and rash 16 (22.5%) were noted. The d-dimer (>0.5 µg/mL) levels were increased in all (100%) patients. Thrombocytopenia (91.5%) was the commonest hematological abnormality and 31 (43.6%) of them had severe thrombocytopenia, 25 (35.2%) patients had low fibrinogen levels (<200 mg/dL) and prothrombin time (PT >16.7 seconds) was prolonged in 20 (28.1%). A total of 42 (59.1%) patients developed MODS, 33 (46.4%) developed septic shock, 24 (33.8 %) had MODS with septic shock, 17 (23.9%) developed overt DIC, and eight (11.2%) died. Severe thrombocytopenia (p = -0.028) and overt DIC (p = 0.045) were significantly associated with septic shock development. CONCLUSION: In the patients admitted with severe scrub typhus; thrombocytopenia was the commonest hematological abnormality. The development of septic shock was significantly associated with severe thrombocytopenia and overt DIC.

Clinical Characteristics and Diagnostic Prediction of Severe Fever with Thrombocytopenia Syndrome and Rickettsiosis in the Co-Endemic Wakayama Prefecture, Japan.

Background and Objectives: The Wakayama prefecture is endemic for two types of tick-borne rickettsioses: Japanese spotted fever (JFS) and scrub typhus (ST). Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne hemorrhagic viral disease with a high mortality rate and is often difficult to differentiate from such rickettsioses. SFTS cases have recently increased in Wakayama prefecture. For early diagnosis, this study aimed to evaluate the clinical characterization of such tick-borne infections in the co-endemic area. Materials and Methods: The study included 64 febrile patients diagnosed with tick-borne infection in Wakayama prefecture between January 2013 and May 2022. Medical records of 19 patients with SFTS and 45 with rickettsiosis (JSF, n = 26; ST, n = 19) were retrospectively examined. The receiver operating curve (ROC) and area under the curve (AUC) were calculated to evaluate potential factors for differentiating SFTS from rickettsiosis. Results: Adults aged ≥70 years were most vulnerable to tick-borne infections (median, 75.5 years; interquartile range, 68.5-84 years). SFTS and rickettsiosis occurred mostly between summer and autumn. However, no significant between-group differences were found in age, sex, and comorbidities; 17 (89%) patients with SFTS, but none of those with rickettsiosis, experienced gastrointestinal symptoms such as vomiting, abdominal pain, and diarrhea. Meanwhile, 43 (96%) patients with rickettsiosis, but none of those with SFTS, developed a skin rash. The AUCs of white blood cells (0.97) and C-reactive protein (CRP) levels (0.98) were very high. Furthermore, the differential diagnosis of SFTS was significantly associated with the presence of gastrointestinal symptoms (AUC 0.95), the absence of a skin rash (AUC 0.98), leukopenia <3.7 × 109/L (AUC 0.95), and low CRP levels < 1.66 mg/dL (AUC 0.98) (p < 0.001 for each factor). Conclusions: Clinical characteristics and standard laboratory parameters can verify the early diagnosis of SFTS in areas where tick-borne infections are endemic.

Mixed genotypes of Orientia tsutsugamushi in conserved genes and a single immune-dominant tsa56 genotype discovered from a patient with scrub typhus in Hainan Island, China: a case report.

BACKGROUND: Orientia tsutsugamushi (O. tsutsugamushi), an obligate intracellular bacterium, is transmitted to humans through infected larval trombiculid mite bites, causing scrub typhus. Mixed genotypes of O. tsutsugamushi in canonical conserved genes were reported in 8-25% of blood samples from patients. Yet, there are few clinical descriptions of these mixed O. tsutsugamushi-infected patients. CASE PRESENTATION: We report a patient with scrub typhus complicated with pulmonary involvement and hepatic dysfunction, who carried mixed genotypes of the conserved genes but had a single immune-dominant 56-kDa type-specific antigen (tsa56) genotype. The patient was successfully recovered by doxycycline treatment. CONCLUSIONS: In this reported case, both patient's eschar and blood samples have repeatedly shown the same results, i.e., no variants were discovered in tsa56 gene that bears multiple hypervariable regions. Whereas the selected highly conserved genes were identified with up to 32 variants in a 2700 base-pair concatenated sequence. The prevalence, disease severity and mechanism of these single-tsa56-genotype mixed infections remain to be investigated on a large scale with more cases.

Neurological Manifestations of Scrub Typhus.

PURPOSE OF REVIEW: The occurrence of cases of scrub typhus is on the rise in South Asian and Southeast Asian countries. The present review discusses neurological complications following scrub typhus to appraise clinicians practicing in endemic regions about considering this treatable disease in the differential diagnosis of acute febrile illnesses, especially when accompanied with clinical neurological features. RECENT FINDINGS: While the association of aseptic meningitis, encephalitis, and meningoencephalitis with scrub typhus is well known, more recently described neurological syndromes associated with scrub typhus include acute disseminated encephalomyelitis, various cranial nerve palsies, cerebellitis, cerebrovascular diseases including cerebral venous sinus thrombosis, transverse myelitis, longitudinally extensive transverse myelitis, Guillain-Barré syndrome, opsoclonus-myoclonus syndrome, parkinsonism, and many more. Early diagnosis is key to successful treatment. While diagnostic confirmation is generally made by the detection of IgM antibody by either ELISA or indirect fluorescent antibody tests, conventional PCR using 56 kDa gene (cPCR) and loop-mediated isothermal amplification assay (LAMP assay), as well as a newly introduced metagenomic next-generation sequencing (mNGS), are currently available for detection of Orientia tsutsugamushi infection in clinically suspected cases. Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. The cutaneous hallmark of the disease is the "eschar." Scrub typhus results in multisystem involvement. Neurological compromise is present in about 20% of scrub typhus patients and affects both the central nervous system and the peripheral nervous system. The postulated underlying mechanisms include direct invasion of the organism, a vasculitis-like process, or an immune-mediated injury. Diagnosis of scrub typhus is confirmed by detection of O. tsutsugamushi IgM antibody in serum. Awareness among clinicians regarding the varied presentations of this disease is very important in order to reduce morbidity and mortality. Co-infection with dengue and/or chickungunya viruses may occur in endemic regions. The history of an acute febrile illness preceding the neurological illness is crucial. A very careful search for the eschar is essential; however, the absence of the skin lesion cannot exclude the diagnosis of scrub typhus. Neurological manifestations mostly respond to doxycycline therapy.

An unusual presentation of scrub typhus in a child: a case report.

BACKGROUND: Scrub Typhus (ST) is an acute, febrile zoonotic disease caused by the bacterium Orientia tsutsugamushi which is endemic to the Asia-Pacific region. Infected adults rarely present with sensorineural hearing loss and otalgia. Though few cases of pediatric cases are known to present with otalgia, no pediatric cases of sensorineural deafness complicating ST have been reported to date. CASE PRESENTATION: A 5-year-old, previously healthy girl presented with a one-week history of high-grade intermittent fever, Headache and right ear pain with a recent onset of reduced hearing. She had a fever up to 39 °C, cervical lymphadenopathy, bilateral pleural effusion with diffuse infiltrations, and mild hepatosplenomegaly with no evidence of rash. Her initial examination was normal except for mildly enlarged tonsils. Unilateral right ear hearing loss was noted using Weber's test. Evidence of progressive, mild anemia, and raised inflammatory markers was noted. Diagnosis of scrub typhus was confirmed by positive detection of Orentia tsutsugamushi IgM antibodies on rapid diagnostic test and the presence of chigger mite in the right external auditory canal on repeat examination. She responded dramatically to the empirical treatment of ceftriaxone and doxycycline. On follow-up, she did not have any residual hearing loss and her ear pain had resolved completely. CONCLUSION: Acute onset hearing loss or severe otalgia with or without findings should be an important diagnostic clue for suspecting scrub typhus in patients who present with a history of fever especially in endemic areas.

Is Hyperuricemia a Marker of Severity of Disease in Scrub Typhus?

AIMS: To study association of hyperuricemia with severity of scrub typhus. METHODS: We studied clinical features, laboratory profile, in hospital course and outcome of 92 patients of scrub typhus and association of hyperuricemia with severity of disease. RESULTS: Of total 92 patients in study group, 66 (71.7%) were females and 26(28.3%) were males. Fever (100%), cough (37%), headache (33%), vomiting (31%), altered sensorium (23%), diarrhea (18%), abdominal pain (16%), myalgia (14%), and seizures (3%) were common clinical features. Eschar was present in 23%. Of total 92 patients 34 (37%) patients had hyperuricemia (HU) and 58 patients had normal serum uric acid levels. The patients of scrub typhus with HU had significantly higher presentation with altered sensorium (35.3%). In HU group, mean TLC, mean serum urea and serum creatinine were higher and mean serum albumin and mean HDL cholesterol were lower than patients of scrub typhus without hyperuricemia. These differences between two groups were statistically significant. Neurological dysfunction, severe sepsis, serum creatinine >3.5mg/dL and involvement of at least single organ was significantly higher in HU group. Total 4 patients (4.3%) died and all had HU. CONCLUSION: Hyperuricemia in patients of scrub typhus was associated with severe scrub typhus. The serum uric acid levels should be done in early course of all patients suffering from scrub typhus. The patients showing hyperuricemia should be monitored closely for early recognition of complications and management aggressively.

Transient cerebral salt wasting following scrub typhus infection- A case report.

Cerebral salt wasting (hyponatraemia associated with renal sodium loss and hypovolumia) has been reported secondary to intra-cerebral pathology and following certain infections. Cerebral salt wasting following typhus infection has been reported rarely. We report a case of transient cerebral salt wasting that occurred during the convalescent phase of scrub typhus infection resulting in severe symptomatic hyponatraemia.

Dengue and scrub typhus co-infection in children: Experience of a teaching hospital in an endemic area.

Background: Dengue fever and scrub typhus are considered an endemic disease in the Indian subcontinent. The epidemiology and clinical presentations are complex and vary each year. Objective: The objective of this study was to estimate the prevalence of coinfection with scrub typhus in children diagnosed with dengue fever. Methods: A retrospective hospital-based, cross-sectional study was done in the Department of Pediatrics of a teaching hospital in Puducherry. All children (0-14 years) who had enzyme-linked immunosorbent assay (ELISA) reported scrub typhus among those diagnosed with dengue fever (NS1Ag or immunoglobulin M ELISA positivity) during 2012-2016. Medical records with incomplete data were excluded from the study. Odds ratio was calculated to find out the association of coinfections. An independent t-test was used to find out the statistical significance. P < 0.05 was considered statistically significant. Results: Atypical features of dengue were present in 250/318 (78.6%) children. Coinfections were seen in 62/318 (19.4%) children. Scrub typhus was the most common (n = 51/62, 82.2%). The chance of scrub typhus in a dengue serology-positive child is significant when the symptoms are atypical or protracted (OR- 2.6, P = 0.033). Conclusion: High index of suspicion should be present in endemic dengue and scrub typhus coinfection.

Investigations of seasonal outbreaks of acute encephalitis syndrome due to Orientia tsutsugamushi in Gorakhpur region, India: A One Health case study.

Gorakhpur division consisting of Gorakhpur and neighboring districts Deoria, Kushinagar and Maharajganj in Uttar Pradesh, India, have been witnessing seasonal outbreaks of acute encephalitis syndrome (AES) among children for the last three decades. Investigations conducted during 2005 identified Japanese encephalitis (JE) virus as an aetiology of AES. With the introduction of JE vaccination and other control strategies, the incidence of JE in the region declined, however, outbreaks of acute febrile illness with neurological manifestations continued to occur. Subsequent investigations identified Orientia tsutsugamushi, as the major aetiology of AES outbreaks in the region. This review details clinical, epidemiological, animal and entomological investigations conducted for AES due to O. tsutsugamushi during 2015 and 2017 in Gorakhpur region. Surveillance of acute febrile illness among children attending peripheral health facilities identified scrub typhus as an important aetiology of febrile illness during monsoon and post-monsoon months. Population-based serosurveys indicated high endemicity of scrub typhus. Entomological studies demonstrated natural infection of O. tsutsugamushi in small animal hosts and vector mites. Children acquired this infection through recent exposure to outdoor environment, while playing, or visiting fields or defecating in open fields. A few of the children with scrub typhus progress to develop CNS manifestations. Hence, early administration of appropriate antibiotics is crucial in preventing progression of AFI due to scrub typhus to AES. The investigations conducted by the multi-disciplinary team helped understand the transmission dynamics of scrub typhus in Gorakhpur division and recommend strategies for its control.

Spectrum of Multiorgan Dysfunction in Scrub Typhus Infection.

OBJECTIVES: We planned this study to determine the clinical spectrum and compare incidence of multiorgan dysfunction in children hospitalized with scrub typhus with other etiologies of tropical fever. DESIGN: Prospective cohort study. SETTING: Pediatric emergency and PICU services of a university teaching hospital situated in the sub-Himalayan region. PATIENT: Children aged 2 months to 14 years with acute undifferentiated fever of more than 5 days. INTERVENTIONS: Detailed fever workup was performed in all children. We compared scrub typhus IgM positive children (cases) with remaining febrile children who were negative for scrub IgM assay (controls) for mortality and morbidity. MAIN RESULTS: We enrolled 224 febrile children; 76 children (34%) were positive for scrub typhus IgM ELISA. Scrub typhus group had a significantly higher incidence of multiorgan dysfunction [OR 3.5 (95% CI 2.0-6.3); p < 0.001] as compared to non-scrub typhus group requiring supportive care. The incidence of altered sensorium [OR 8.8 (95% CI 3.1-24.9)], seizures [OR 3.0 (95% CI 1.1-8.3)], acute respiratory distress syndrome [OR 17.1 (95% CI 2.1-140.1)], acute renal failure (5% vs. 0%), meningitis [OR 6.2 (95% CI 1.2-31.6)], thrombocytopenia [OR 2.8 (95% CI 1.5-5.1)], transaminitis [OR 2.7 (95% CI 1.6-4.8)], requirement of oxygen [OR 17.8 (95% CI 4.0-80.3)], positive pressure support [OR 3.7 (95% CI 1.2-10.5)] and shock requiring inotropes [OR 3.0 (95% CI 1.3-6.7)] was significantly higher in scrub typhus group as compared to the non-scrub typhus group (Table 1). CONCLUSIONS: Pediatric scrub typhus who were hospitalized had severe systemic manifestations when compared to other causes of fever.