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.

Prevalence, Clinico-Laboratory Features and Outcomes of Paediatric Scrub Typhus Cases in a Tertiary Care Centre in Eastern India: A prospective observational study.

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 clinico-laboratory 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.

Two complicated cases of severe scrub typhus, eschar- a non-negligible sign: Case reports and literature review.

RATIONALE: Scrub typhus is a mite-borne, acute febrile disease caused by Orientia tsutsugamushi. The endemic areas of scrub typhus are expanding, both globally and in China. Patients who are not treated promptly, are likely to die of multiple organ dysfunction syndrome. PATIENT CONCERNS: Case I A 61-year-old female patient complained of sudden chest tightness and shortness of breath accompanied by fever for 6 days. Case II A 54-year-old male patient complained of fever and cough for 4 days and renal insufficiency for 2 days. DIAGNOSES: Scrub typhus, multiple organ dysfunction syndrome. INTERVENTIONS: After the definite diagnosis, both patients were treated with doxycycline and various organ supports. OUTCOMES: The patient in case I was ultimately not salvageable. The patient in case II was successfully cured by the prompt administration of doxycycline along with continuous renal replacement therapy. LESSONS: With early diagnosis and treatment, patients can completely recover. Eschar, a characteristic sign of scrub typhus, is often overlooked, leading to delayed diagnosis and regrettable outcomes.

Scrub typhus with hemorrhagic stroke: a case report.

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.

Acute intravascular haemolysis associated with scrub typhus.

Scrub typhus, a prevalent tropical infection, may sometimes manifest with unusual complications. Here, we present the case of a young man who was admitted to our facility with a fever for the past 3 days and passage of dark-coloured urine since that morning. On investigation, we identified intravascular haemolytic anaemia. Through meticulous examination, a black necrotic lesion (eschar) was discovered on his right buttock, a pathognomonic sign of scrub typhus infection. Treatment was initiated with oral doxycycline 100 mg two times a day. Subsequently, diagnosis of scrub typhus was confirmed through positive results from scrub typhus IgM via ELISA and PCR analysis from the eschar tissue. The patient responded well to oral doxycycline and his symptoms resolved within the next few days. This case highlights severe intravascular haemolysis associated with scrub typhus infection.

A case of scrub typhus with meningitis as the onset: Case report and literature review.

RATIONALE: Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon. PATIENT CONCERNS: A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation. DIAGNOSES: The patient was diagnosed with a central nervous system infection. INTERVENTIONS: Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders. OUTCOMES: Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided. CONCLUSIONS: The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective. LESSION: Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.

Orientia tsutsugamushi: An Unusual Intracellular Bacteria-Adaptation Strategies, Available Antibiotics, and Alternatives for Treatment.

During evolution Orientia tsutsugamushi became a smarter obligate bacterium to establish as intracellular pathogens. O. tsutsugamushi is a human pathogenic bacterium responsible for 1 billion infections of scrub typhus. Several novel mechanisms make this bacterium unique (cell wall, genetic constitutions, secretion system, etc.). In 2007, O. tsutsugamushi Boryong was pioneer strain for whole-genome sequencing. But the fundamental biology of this bacterial cell is a mystery till date. The unusual biology makes this organism as model for host cell interaction. Only a few antibiotics are effective against this intracellular pathogen but emergence of less susceptibility toward antibiotics make the situation alarming. The review was captivated to highlight the unusual aspects of adaptation, antibiotics, and drugs beyond antibiotics.

Ocular inflammation in tsutsugamushi disease - a case report.

A 64-year-old male, working at a mountain site in Taitung County, suffered from primary open angle glaucoma (POAG) post trabeculectomy with well-controlled intraocular pressure (IOP) in both eyes (OU). He presented with headache accompanied by red eyes (OU) for 10 days. Physical examination revealed fever up to 38.2°C, neck stiffness, one eschar at the left forearm and another at the left ankle. Abnormal laboratory data indicated bacterial infection with central nervous system involvement. Ophthalmic examination showed elevated IOP, moderate conjunctival congestion, subconjunctival hemorrhage, anterior uveitis, cotton-wool spots on the retina and multiple white dots on the temporal retina (OU). Under the impression of uveitis in tsutsugamushi disease with atypical meningitis, oral doxycycline, anti-glaucoma and anti-inflammation eye drugs were prescribed. IOP returned to 12 mmHg and anterior uveitis subsided. The lesions of cotton-wool spots on the retina disappeared within 2 weeks, but multiple white dots remained persistently on the temporal retina.

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.

Digital Gangrene Associated with Scrub Typhus: A Case Series.

Rickettsial diseases cover a broad spectrum of illnesses. Scrub typhus is present worldwide, and Orientia tsutsugamushi is the causative agent of this chigger mite-borne infectious illness. Infections exhibit a range of severity, from mild illness to the more severe manifestation of multiorgan failure. We report three cases of scrub fever (55-year-old female, 63-year-old female, and 29-year-old male), all cases developed focal or pan-digital gangrene. All cases were successfully treated by administering doxycycline and additional supportive measures. Digital gangrene is uncommon in scrub typhus. Clinical suspension for early diagnosis and appropriate treatment may avoid further complications.

Case report of scrub typhus with bilateral acute sensorineural hearing loss and cerebral salt-wasting disease.

Scrub typhus is a re-emerging and endemic disease in the Asia Pacific region caused by Orientia tsutsugamushi. We present a 65-year-old male from Sri Lanka who presented with fever, bilateral acute sensorineural hearing loss, and confusion. On examination, he was dehydrated. Significant orthostatic hypotension and an eschar were noted. Investigations revealed hyponatraemia with elevated urine sodium, reduced serum osmolality, and normal urine osmolality suggestive of cerebral salt wasting. After initial hydration with 0.9% NaCl, hyponatraemia was corrected with 3% NaCl. Oral doxycycline was prescribed, and he showed dramatic clinical improvement. A diagnosis of typhus must be considered in a patient presenting with a febrile illness and acute hearing loss. Cerebral salt-wasting disease should be considered in a patient with typhus who develops hyponatraemia with dehydration. Furthermore, acute sensorineural hearing loss in both ears is an important manifestation of the disease.

Doxycycline vs azithromycin in patients with scrub typhus: a systematic review of literature and meta-analysis.

INTRODUCTION: Scrub typhus is a bacterial mite-borne disease associated with poor clinical outcomes if not treated adequately. The study aimed to compare the time to defervescence, clinical failure, mortality and treatment-related adverse effects of two common drugs (doxycycline and azithromycin) used for its treatment. METHODOLOGY: This was a systematic review and meta-analysis. All studies up to 20.03.2023 were screened for eligibility in Pubmed and Embase using a search string containing terms related to scrub typhus, doxycycline and azithromycin. After two phases of screening, all comparative studies where doxycycline and azithromycin were used to treat scrub typhus were included. The studies were critically appraised using standardised tools, and a meta-analysis was performed for time to defervescence (primary outcome), clinical failure, mortality and treatment-related adverse effects. RESULTS: Of 744 articles from two databases, ten were included in the meta-analysis. All but two studies had a high risk of bias. The meta-analysis for time to defervescence had a high heterogeneity and did not show any significant difference between doxycycline and azithromycin arms [Mean difference of -3.37 hours (95%CI: -10.31 to 3.57), p=0.34]. When the analysis was restricted to studies that included only severe scrub typhus, doxycycline was found to have a shorter time to defervescence [mean difference of -10.15 (95%CI: -19.83 to -0.46) hours, p=0.04]. Additionally, there was no difference between the two arms concerning clinical failure, mortality and treatment-related adverse effects. CONCLUSION: The current data from studies with a high risk of bias did not find statistically significant differences in clinical outcomes between doxycycline and azithromycin for scrub typhus.

A CARE-compliant article: A case report of unusual eschar and extensive soft tissue necrosis in Tsutsugamushi disease.

RATIONALE: Tsutsugamushi disease is a common infectious disease in the Northern Hemisphere. A patient infected with tsutsugamushi disease will show a characteristic clinical course with eschar formation, which is mostly small and self-limited in nature without causing major problems. We report a rare case of unusually extensive necrosis started from a small eschar. PATIENT CONCERNS: In this report, a 65-year-old female patient with a history of diabetes mellitus present an 8 × 6 cm-sized huge eschar and extensive soft tissue necrosis aggravated from a small eschar. Also, there were 3 other small eschars in the scalp and left flank area. In early July, she was farming in a field in Hongseong-gun, South Korea. She had been treated at another hospital for 2 weeks. However, the eschar became bigger and worse. DIAGNOSES: After admission, escharectomy was performed and extensive soft tissue necrosis was identified. Orientia tsutsugamushi antibody tests were positive from blood test. Providencia rettgeri and Enterococcus faecalis were detected in a tissue bacterial culture test. INTERVENTION: While using oral azithromycin and intravenous imipenem/cilastatin, the necrosis of the thigh was excised and covered by lateral femoral circumflex artery based myocutaneous Keystone flap. OUTCOMES: The remaining small eschars recovered spontaneously, the large eschars that had caused necrosis were successfully treated, and all other clinical symptoms improved without complications. LESSONS: For unusual eschar of an unknown cause, especially in patients with uncontrolled diabetes or immunocompromised, the possibility of Tsutsugamushi should be considered. Careful physical examination and proper management should be performed as soon as possible.

Clinical treatment of patients with scrub typhus-induced liver injury and intracranial infection.

Scrub typhus is an infectious disease caused by Orientia tsutsugamushi, a bacterium within the family Rickettsiaceae. The clinical symptoms are usually acute and are characterized by fever, eschar formation or ulceration, local or generalized lymphadenopathy, and rash. Because of the extensive damage to small blood vessels throughout the body, scrub typhus can involve multiple systems and organs, causing damage to the respiratory, digestive, and nervous systems and inducing kidney and liver dysfunction. Death can occur in severe cases. We herein report two cases of scrub typhus with liver damage and intracranial infection. Among patients with scrub typhus, the risk of death is significantly higher in those who develop liver injury and intracranial infection. However, there are few reports on the treatment of patients with liver injury and intracranial infection caused by scrub typhus, and relevant treatment experience is thus lacking. Our clinical case report helps to fill the knowledge gap in this area.

Macrolides versus other antibiotics in pediatric scrub typhus: A meta-analysis.

BACKGROUND: While Doxycycline is the recommended drug for treating scrub typhus, there is a growing trend of using Macrolides and Other antibiotics due to their perceived advantages. In this study, we compared the efficacy of Macrolides versus Other antibiotics in the treatment of pediatric scrub typhus. METHODS: Meta-analysis of randomized controlled trials (RCTs) with GRADE (Grading of Recommendations, Assessment, Development and Evaluation) application. Major databases were searched till 30th December 2022. Children of all age groups were included. Primary outcomes included mortality rate and time to defervescence (h). RESULTS: Of the 103 citations retrieved, 5 trials, including 383 children up to 15 years of age with probable and confirmed cases of scrub typhus, were included. None of the trials reported mortality rate. The pooled results from the trials found no significant difference between Azithromycin and Other antibiotics for any of the outcome measures. The certainty of evidence for the primary outcome was deemed to be of "very low certainty", while the certainty of evidence for the secondary outcomes ranged from "low to moderate certainty". CONCLUSIONS: The current meta-analysis revealed that there was no significant difference between Azithromycin and Other antibiotics (such as Doxycycline and Chloramphenicol) in the treatment of scrub typhus in children. However, it's important to note that the evidence generated for the primary outcome was of "very low certainty". PROSPERO REGISTRATION NUMBER: CRD42021276577.

Three cases of scrub typhus with hemorrhage: a case report and literature review.

Scrub typhus (ST) is an acute focal infectious disease that is caused by Orientia tsutsugamushi. The Asia-Pacific region is an area of relatively high incidence. There is a high incidence in China, principally owing to the disease being endemic in the south of the country. The main source of ST infection is rats, which act as reservoirs of infection after being bitten by the chigger mite, and the human population is generally susceptible to the disease. ST can be controlled and treated successfully if antibiotics are administered in a timely manner. However, because it does not have a specific clinical manifestation, it is difficult to distinguish ST from other febrile diseases in clinical practice. Therefore, rapid diagnostic methods are still needed to help clinicians make a timely diagnosis. Here, we share three cases of patients with ST who experienced hemorrhage, but did not have typical skin lesions, such as eschar and ulcer, early in the course of their disease, and review the relevant literature regarding ST. We conclude that clinicians should pay attention to the risk of hemorrhage associated with this disease, and emphasize the importance of making an early diagnosis.

Open-labeled Randomized Controlled Trial on Efficacy of Azithromycin Versus Doxycycline in Pediatric Scrub Typhus.

BACKGROUND: Doxycycline (DX) is the first-line therapeutic agent for scrub typhus. Macrolides, especially azithromycin (AZ), have been found to be equally efficacious as DX for treating scrub typhus in adults. We conducted this study to compare the efficacy of AZ versus DX in pediatric scrub typhus. STUDY DESIGN: Open-label randomized controlled trial. METHODS: Children 1-14 years of age suffering from acute febrile illness of ≥5 days and with a positive scrub IgM serology were randomized to receive either DX (2.2 mg/kg/dose twice daily in <40 kg; 100 mg BD in >40 kg for 7 days) or AZ (10 mg/kg/day for 5 days). The primary outcome was defervescence within 7 days of DX or 5 days of AZ. RESULTS: We had 75 children randomized and analyzed using an intention-to-treat approach and 60 children analyzed via per-protocol analysis. The proportion of children achieving defervescence was comparable in 2 groups [per-protocol analysis: 90.9% in the DX group vs. 96.3% in the AZ group, RR: 0.94 (95% CI: 0.83-1.08)]. On Kaplan-Meier curves, AZ showed a significantly higher probability of defervescence at any time point during treatment as compared with DX (log-rank test P value 0.035). CONCLUSION: AZ and DX had comparable rates of defervescence among children with scrub typhus. Trial registration No.: CTRI/2020/01/022991.