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.

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.

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.

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.

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.

Retrospective analysis of clinico-laboratory parameters, outcome and predictors of scrub typhus co- infection in covid-19 affected children.

The objective of this study was to describe clinico-laboratory parameters, outcome and predictors of scrub typhus co- infection in COVID-19 affected children. Ours was a retrospective analysis done in a tertiary care pediatric COVID facility. COVID-19 positive children in the age group of 1 month to 12 years who were tested for scrub typhus co-infection between May to August 2020 were included in the study. In all positive cases, clinical, laboratory, treatment and outcome data were analyzed. Relevant data were compared between scrub typhus confirmed, and suspected but negative patients. All six patients with co-infection had fever for >5 days and four had features of cerebral involvement. These had lymphocytic pleocytosis in cerebrospinal fluid (CSF) analysis and two had eschar. Screening for scrub typhus in persistently febrile children residing in highly endemic areas is highly recommended.

Case Report: Optic neuritis as the initial presentation of Orientia tsutsugamushi infection detected by metagenomic next-generation sequencing.

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi infection, and typically manifested as fever, eschar, lymphadenopathy, rash, and other flu-like signs. Ocular involvement was not uncommon, and mostly occurred at post-fever or recovery stage in scrub typhus cases. We hereby report a case of scrub typhus presenting as unilateral optic neuritis (ON). A 56-year-old man going wild fishing nearly every day complained of a blurred vision and an inferior visual field defect in the right eye two or three days after an insect-bite like shin induration in his left leg. He was diagnosed as ON, and treated with dexamethasone in the local hospital. Unfortunately, his right eye vision progressively deteriorated during steroid therapy. Three days after steroid therapy ceased, he suffered from a high fever and painful subcutaneous masses in the left groin. Peripheral blood test by metagenomic next-generation sequencing (mNGS) was positive for Orientia tsutsugamushi, but negative for other pathogens. The diagnosis was then revised to scrub typhus and ON. His systemic symptoms rapidly disappeared after oral doxycycline and omadacycline therapy. However, his right eye vision continuously deteriorated to hand motion. Further serum tests for aquaporin 4-IgG antibody and myelin oligodendrocyte glycoprotein-IgG antibody were both negative, but for anticardiolipin IgM and beta-2-glycoprotein-I IgM were both positive. The patient's right eye vision gradually improved after doxycycline combined with steroid pulse therapy. Our case indicates that ON in scrub typhus cases may present as a parainfectious inflammation, and that mNGS is a useful and valuable method for early diagnosis of scrub typhus.