Real-world utility of serological tests in patients with suspected scrub typhus in the Republic of Korea:A single-center,retrospective,observational study

Objective:Serological tests are widely used for scrub typhus diagnosis;however,their limitations are evident.This study aims to assess their practical value in clinical settings.Methods:We analyzed the data of adult patients with suspected scrub typhus who visited a tertiary care hospital in the Republic of Korea from September to December from 2019 to 2021.The included patients had an acute fever and at least one of the following ten secondary findings:myalgia,skin rash,eschar,headache,thrombocytopenia,increased liver enzyme levels,lymphadenopathy,hepatomegaly,splenomegaly,and pleural effusion.The diagnoses were grouped as scrub typhus or other diseases by two infectious disease physicians.Results:Among 136 patients who met the eligibility criteria,109 had scrub typhus and 27 had different diseases.Single and paired total antibodies using immunofluorescence assay(IFA),and total antibodies using immunochromatography-based rapid diagnostic testing(ICT)were measured in 98%,22%,and 75%of all patients,respectively.Confirmation using paired samples for scrub typhus was established at a median of 11[interquartile range(IQR)10-16]days following the first visit.Among the 82 admitted patients,the median admission time was 9(IQR 7-13)days.According to IFA,58(55%)patients with scrub typhus had total immunoglobulin titers≥1:320,while 23(85%)patients with other disease had titers<1:320.Positive ICT results were observed in 64(74%)patients with scrub typhus and 10(67%)patients with other diseases showed negative ICT results.Conclusions:Serological testing for scrub typhus is currently insufficient for decision-making in clinical practice.

Omadacycline in the treatment of scrub typhus:Three case reports

BACKGROUND Scrub typhus is a naturally occurring acute infectious disease that is primarily transmitted through the bites of chiggers or larval mites infected by Orientia tsutsugamushi(O.tsutsugamushi).Omadacycline,a novel tetracycline,exhibits potent antibacterial efficacy against both typical bacteria and atypical pathogens.However,omadacycline application in the treatment of scrub typhus remains limited.CASE SUMMARY In the present work,we report several cases of scrub typhus,with the main clinical symptoms being fever,the formation of eschars or ulcers,local or systemic lymphadenopathy,headache,myalgia and rash.Blood samples were collected before omadacycline was administered,and O.tsutsugamushi infection was confirmed through targeted next-generation sequencing(tNGS).After two days of treatment,the patients’symptoms,including fever,were alleviated,with no adverse drug reactions.CONCLUSION tNGS is an effective method for diagnosing scrub typhus.Omadacycline can be considered an alternative option for antiinfective therapy in patients with O.tsutsugamushi infections.

Myositis and rhabdomyolysis in scrub typhus infection: A case report

Rationale:Fever with myositis and rhabdomyolysis is a medical emergency requiring prompt diagnosis and management.Scrub typhus associated myositis with rhabdomyolysis is rare.Patient concerns:A 36-year-old female presented with intermittent fever up to 38.6℃,jaundice and progressive weakness of all four limbs.Diagnosis:Scrub typhus associated myositis and rhabdomyolysis.Intervention:Doxycycline 100 mg twice daily and injection of ceftriaxone 1 gm twice daily along with continuous intravenous fluids.Outcome:Fever resolved with normalization of liver function and recovery of muscle power.Lessons:Presence of myositis and rhabdomyolysis is uncommon in scrub typhus;high clinical suspicion should be kept in patients with atypical manifestations of scrub typhus.

Epidemiology and clinico-laboratory manifestations of scrub typhus in Hadoti region of Rajasthan,India:A cross-sectional study

Objective:To study epidemiology,clinical manifestations,and laboratory parameters of scrub typhus in Hadoti region of Rajasthan,India.Methods:A cross-sectional study was conducted on 50 patients with scrub typhus between August 2022 and November 2022.Scrub typhus was diagnosed by ELISA IgM scrub typhus antibody.The data about demography,vital parameters,and lab investigations were collected and analyzed.Results:Ninety-two percent of the patients were from a rural background(92%),86% were farmers and the majority were females.Most patients were 40-60 years old.The major complaints were fever(100%),myalgia(100%),headache(82%),and body swelling(80%).Major complications were pneumonia(68%),multiple organ dysfunction syndrome(62%),hepatitis(44%),and acute kidney injury(42%).Triglyceride levels were>200 mg/dL in 80% of patients,albumin<3.5 g/dL in 98% and eschar mark was present in 24%of patients.Conclusions:Scrub typhus is a serious acute febrile illness that can lead to multi-organ dysfunction and is associated with significant mortality.Increasing awareness regarding disease in endemic regions,early screening of patients,and treatment as early as possible could help prevent the patient from severe life-threatening complications.

A review of the epidemic and clinical study on scrub typhus in China(2010-2020)

Scrub typhus is an acute febrile vector-borne zoonotic disease caused by the obligate intracellular growth bacterium Orientia tsutsugamushi(Ot).Mites are the primary vectors and rodents play a pivotal role in the transmission of scrub typhus.Due to the climate warming,increased human activity and other factors,cases of scrub typhus have been increased sharply during the past decade in China,especially in the northern China.To understand the incidence trend,epidemic pattern,clinical sign,diagnosis and therapy of this diseases as well as genotype evolution of Orientia tsutsugamushi,we summarized and analyzed the current knowledge of scrub typhus in China from 2010 to 2020.The data indicated that the dominate genotypes of scrub typhus in China were Karp,Kato and Gilliam.Although the disease was distributed national wide,Yunnan,Guangzhou and Fujian showed the highest incidence rate.The main vector of scrub typhus in southwest,middle east and southeast of China appeared a geographic preference respectively.Seasonal timing,age and occupation were the key factors that relate to the peak incidence of scrub typhus.Notably,farmer was the occupation with the highest risk of Ot infection.Further study on the epidemic characteristics,risk factors,diagnosis and treatments of scrub typhus will be of benefit to a comprehensive guideline for prevention and control of this ancient disease.

Scrub typhus:pathophysiology,clinical manifestations and prognosis

Scrub typhus is a zoonosis caused by the pathogen Orientia tsutsugamushi(O.tsvtsugamushi). The disease has significant prevalence in eastern and Southeast Asia.Usually presenting as an acute febrile illness,the diagnosis is often missed because of similarities with oilier tropical febrile infections.Many unusual manifestations are present,and these are described in this review,together with an outline of current knowledge of pathophysiology.Awareness of these unusual clinical manifestations will help the clinician to arrive at an early diagnosis,resulting in early administration of appropriate antibiotics.Prognostic indicators for severe disease have not yet been clearly established.

Pancreatic abscess following scrub typhus associated with multiorgan failure

Clinical severity of scrub typhus ranges from mild to fatal. Acute pancreatitis with abscess formation is a rare complication among patients with scrub typhus. This paper reports a case of scrub typhus in a 75 years old man with acute pancreatitis with abscess formation and multiorgan failure. Abdominal computed tomography showed multiple infected pancreatic pseudocysts with periopancreatic infiltration. Multiorgan failure was successfully treated with doxycycline, ceftriaxone, and supportive management. The pancreatic abscess was successfully drained percutaneously and the sizes of pseudocysts decreased remarkably.

Neglected scrub typhus:An updated review with a focus on omics technologies

Scrub typhus is a neglected disease and one of the most serious health problems in the Asia-Pacific region.The disease is caused by an obligate intracellular bacteria Orientia tsutsugamushi,which is transmitted by chigger bites or larval mite bites.Scrub typhus is a threat to billions of people worldwide causing different health complications and acute encephalitis in infants and growing children.The disease causes multiple organ failure and mortality rates may reach up to 70%due to a lack of appropriate healthcare.Currently available genome and proteome databases,and bioinformatics methods are valuable tools to develop novel therapeutics to curb the pathogen.This review discusses the state-of-the-art of information about Orientia tsutsugamushi-mediated scrub typhus and delineates the role of omics technologies to develop drugs against the pathogen.The role of proteome-wide in silico approaches for the identification of therapeutic targets is also highlighted.

Comparison of a rapid diagnostic test and microimmunofluorescence assay for detecting antibody to Orientia tsutsugamushi in scrub typhus patients in China

Objective:To evaluate the detection of IgM and IgG antibodies to Orientia tsutsugamushi(O. tsutsugamushi) by rapid diagnostic test(RDT) and microimmunofluorescence assay(ml FA). Methods:RDT using a mixture of recombinant 56-kDa proteins of O.tsutsugamushi and mIFA assay were performed on 20 patients from Fujian and 13 patients from Yunnan Province,and 82 sera samples from healthy farmers in Anhui Province and Beijing City in 2009.Comparison of the RDT and mIFA assay was performed by using X test and the P level of 【0.05 was considered to be significance.Results:Among these 82 normal sera samples,the specificity of RDT was 100%for both IgM and IgG tests.In 33 samples from patients with scrub typhus,5 cases were positively detected earlier by RDT than by mIFA in IgM test,and 2 cases were positive in IgG test.Sensitivities of RDT were 93.9%and 90.9%for IgM and IgG,respectively.The sensitivity of combination lest of IgM and IgG was 100%.Geometric mean titer diluted sera from confirmed cases by IFA and RDT assay were 1:37 vs.1:113(P【0.001) in IgM test and 1:99 vs.1:279 (P【0.05) in IgG test.Conclusions:RDT is more sensitivite than mIFA in the early diagnosis of scrub typhus and it is particularly applicable in rural areas.

Circulatory and hepatic failure at admission predicts mortality of severe scrub typhus patients: A prospective cohort study

Objective:To study the spectrum and outcome of severe scrub typhus in adult patients and to predict the hospital mortality by organ failure on admission.Methods:This was a prospective observational cohort study conducted between July 2017 and October 2020 at the medical emergency centre of PGIMER,Chandigarh,India.One hundred and twenty-six patients aged≥13 years were diagnosed with scrub typhus.Severe disease was defined as the presence of organ failure based on the Sequential Organ Failure Assessment(SOFA)score on admission.Results:About two-thirds of the patients were from geographic regions outside the endemic sub-Himalayan belt.Fever(99.21%)and dyspnea(79.36%)were the most frequent complaints.Respiratory failure(81.75%)was the most common organ failure,followed by hepatic(52.38%),coagulative(47.62%),circulatory(33.33%),renal(21.43%),and cerebral dysfunction(13.49%).The median(Q1,Q3)SOFA score was 8(6,9),and 48.41%of the patients had a quick-SOFA score≥2.Organ supports with invasive ventilation(40.48%),vasopressors(36.51%),and renal replacement therapy(7.14%)were frequently required.The in-hospital mortality was 11.90% and was independently predicted by circulatory and hepatic failures on multivariate logistic regression(OR 11.12,95%CI 1.73-71.31 and OR 8.49,95%CI 1.18-61.41,respectively).Conclusions:Most patients had pulmonary dysfunction;circulatory or hepatic failure on admission strongly predicts death.

Scrub typhus hepatitis confirmed by immunohistochemical staining

Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi （0. tsutsugamushi）. We report herein the case of a woman who presented with fever and elevated serum levels of liver enzymes and who was definitively diagnosed with scrub typhus by his- topathological examination of liver biopsy specimens, serological tests and nested polymerase chain reaction. Immunohistochemical staining using a monoclonal an- ti-O. tsutsugamushi antibody showed focally scattered positive immunoreactions in the cytoplasm of some hepatocytes. This case suggests that scrub typhus hepatitis causes mild focal inflammation due to direct liver damage without causing piecemeal necrosis or interface hepatitis. Thus, scrub typhus hepatitis differs from acute viral hepatitis secondary to liver damage due to host immune responses, which causes severe Iobular disarray with diffuse hepatocytic degeneration, necrosis and apoptosis as well as findings indicative of hepatic cholestasis, such as hepatic bile plugs or brown pigmentation of hepatocytes.

Massive small bowel bleeding caused by scrub typhus in Korea

A 79-year-old man was diagnosed with scrub typhus based on fever,eschar,skin rash and a markedly elevated serum tsutsugamushi antibody and doxycycline was started.Five days later,hematochezia developed and multiple small bowel ulcerations with hemorrhage were seen on colonoscopy.Despite intensive therapy,the massive hematochezia worsened and the distal small bowel was resected.Multiple ulcerated lesions were identified pathologically as vasculitis caused by scrub typhus.This is the first reported case of pathologically proven small bowel involvement in scrub typhus infection.

Spectrum of cardiac manifestations and its relationship to outcomes in patients admitted with scrub typhus infection

AIM To study the spectrum of cardiac manifestations in scrub typhus infection and assess its relationship to outcomes.METHODS Demographic data, electrocardiographic(ECG) changes, left ventricular (LV) systolic and diastolic function, myocardial injury (defined as troponin T > 14 pg/mL), and pericardial effusion were documented. Myocarditis was diagnosed when myocardial injury was associated with global LV systolic dysfunction. The relationship between myocarditis and outcomes was assessed using logistic regression analysis and expressed as odds ratio(OR) with 95%CI.RESULTS The cohort(n = 81; 35 males) aged 49.4 ± 16.1 years(mean, SD) presented 8.1 ± 3.1 d after symptom onset. The APACHE-Ⅱ score was 15.7 ± 7.0. Fortyeight (59%) patients were ventilated, and 46 (56%) required vasoactive agents. Mortality was 9.9%. ECG changes were non-specific; sinus tachycardia was the most common finding. Myocardial injury was evident in 61.7% of patients and LV systolic dysfunction in 30.9%. A diagnosis of myocarditis was made in 12.3%. In addition, seven patients with regional wall motion abnormalities had LV systolic dysfunction and elevated cardiac enzymes. Mild diastolic dysfunction was observed in 18 (22%) patients. Mild to moderate pericardial effusion was seen in 51%. On multivariate logistic regression analysis, patients with myocarditis tended to be older (OR = 1.04, 95%CI: 0.99-1.09), had shorter symptom duration (OR = 0.69, 95%CI: 0.49-0.98), and tended to stay longer in hospital(OR = 1.17, 95%CI: 0.98-1.40). Myocarditis was not associated with increased mortality.CONCLUSION In scrub typhus infection, cardiac manifestations are frequent and associated with increased morbidity but not mortality.

Public knowledge,practices and perceptions on typhus fevers in Southern Sri Lanka

Objective:To assess public knowledge,practices and perceptions on typhus fevers in Sri Lanka.Methods:A descriptive study was done in four selected typhus-prone areas in Southern Sri Lanka.A mixed-method was employed using face-to-face interviews and questionnaire-based surveys among confirmed cases of typhus and at-risk populations,respectively.Frequencies,percentages,and means were used to characterize socio-demography and evaluate disease awareness.Results:The lay terms for typhus fevers reported in the studied region were“peacock fever”,“tick fever”and“bird fever”.A total of 499 subjects participated[mean±SD,(45±16)years]in the questionnaire-based survey,and 13.6%(n=68)reported past experience of typhus fever,1.2%(n=6)identified the disease as“typhus”while 58.7%(n=293)and 11.8%(n=59)knew it as‘peacock fever’and‘tick fever’,respectively.The etiological agent was unknown to 95.2%(n=475),but 53.5%(n=267)were aware that it was vector-borne.Fever(57.3%,n=286),eschar(35.7%,n=178),headache(22.0%,n=267)and myalgia(19.2%,n=96)were identified as key symptoms.Past disease experience was significantly associated with higher awareness of the main disease symptoms(fever:χ^(2)=15.713,P<0.001;headache:χ^(2)=19.447,P<0.001;lymphadenopathy:Fisher’s exact test,P=0.023;eschar:χ^(2)=12.049,P<0.001).None knew of any disease prevention methods.Participants with a past history of typhus fever had sought treatment at state hospitals(55.9%,38/68)and private sector hospitals(5.9%,4/68).Conclusions:Public awareness on preventive practices for typhus fevers was rare among the participants though vector-borne aspect was known to many.Clinical disease awareness was deficient among those without past experience of typhus fever.Community sensitization on vector avoidance strategies is highly recommended.

Manifestation of acute peritonitis and pneumonedema in scrub typhus without eschar:A case report

BACKGROUND Scrub typhus is an acute infectious disease caused by rickettsia infection.The diagnosis is based on eschar,and clinical manifestations can range from asymptomatic to multiorgan dysfunction.CASE SUMMARY We report the case of a 35-year-old man living in Zhuhai,Guangdong,China,who had repeated high fever with a maximum body temperature of 40.2°C and elevated white blood cells and procalcitonin levels.After 7 d of persistent high fever,the patient developed rash,abdominal pain,and symptoms of peritonitis.Within 24 h after admission,the patient developed diffuse peritonitis and pneumonedema,requiring ventilator support in the intensive care unit.However,there was no eschar on the body,and the first Weil-Felix test was negative.Taking into account that the patient had a history of jungle activities,doxycycline combined with meropenem was selected.The patient improved,healed,and was discharged after a week.The diagnosis of scrub typhus was confirmed by a repeat Weil-Felix test(Oxk 1:640),and pathology of the appendix resected by laparotomy suggests vasculitis.CONCLUSION This rare presentation of peritonitis,pulmonary edema,and pancreatitis caused by scrub typhus reminds physicians to be alert to the possibility of scrub typhus.

Association between scrub typhus encephalitis and diffusion tensor tractography detection of Papez circuit injury:A case report

BACKGROUND It is difficult to restore the cognitive functions of patients with impaired cognition caused by brain injury.Diffusion tensor imaging can visualize the integrity of neural tracts in the white matter(WM)three-dimensionally.It is unclear whether encephalitis following scrub typhus damages the WM.For the first time,we aimed to report diffusion tensor tractography(DTT)findings in a chronic patient with cognitive impairment following scrub typhus encephalitis,which revealed injury to the Papez circuit of the WM.CASE SUMMARY A 70-year-old male patient was affected by encephalitis caused by scrub typhus that occurred 23 years ago.He had poor cognition and his clinical examination findings were as follows:Mini-Mental Status Examination score,14;and handgrip strength(right/left,kg),32.3/31.3.DTT revealed serious injuries of the left thalamocingulate tract and right mammillothalamic tract in the Papez circuit,and a partial injury of the anterior part of the fornix.CONCLUSION Using DTT,we found a relationship between cognitive impairment and the integrity of the Papez circuit following scrub typhus.

In Search of Scrub Typhus: A Prospective Analysis of Clinical and Epidemiological Profile of Patients from a Tertiary Care Hospital in New Delhi

Introduction: Scrub typhus is a febrile illness caused by Orientia tsutsugamushi which is transmitted by the larval stage of trombiculid mites. It has varied manifestations ranging from mild disease to fatal illness. The classical manifestations include fever, rash, lymphadenopathy and eschar. Serology is the preferred diagnostic tool with indirect immunofluorescence assay (IFA) as the current gold standard. Material & Methods: A total of 229 clinically suspected cases of Scrub typhus from 15th of October 2013 to 15th of October 2015 were enrolled in the study. Clinical, epidemiological and laboratory data of the patients were collected and analysed. The method for diagnosis was IgM immunofluorescence assay. Results: A total of 33 cases (14.4%) of scrub typhus were detected. Most of the cases (87%) presented in the months of September to November. Fever of >39°C was seen in all 33 cases. Rash and eschar were seen in 24.2% and 18.2% cases, respectively. Lymphadenopathy (18.2%), hepatomegaly (48.5%), splenomegaly (21.2%) and icterus (15.2%) were seen in some cases. Pulmonary manifestations were noted in 69.7% of cases. Acute kidney injury (18.2%), encephalitis (21.2%), and myocarditis (15.15%) were the other complications observed. Common haematological abnormalities noted in patients of scrub typhus were anaemia (45.6%), leucocytosis (45.6%), thrombocytopenia (48.5%) and transaminitis (54.5%). 10 cases were treated by azithromycin while doxycycline was used for treatment in 28 cases. Conclusion: The nonspecific symptoms and lack of classical manifestations make the diagnosis of scrub typhus difficult. There is a definite need to increase awareness and heighten the suspicion, especially in the light of increasing number of patients presenting with atypical manifestations.

A Case Report of Scrub Typhus: Secondary Acute Arrest of Hemopoiesis with Multiple Organ Dysfunction Syndromes

Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi (O. tsutsugamushi) in which humans are accidental hosts. Acute arrest of hemopoiesis (AAH) always manifests in pancytopenia and with supportive treatment or inducement removal, the AAH patients would show significant improvement in blood routine for about a week. As a rapidly progressive and potentially life-threatening organ function disorder syndrome, multiple organ dysfunction syndrome (MODS) is often induced by many factors including infection, illness and injury. We received a rare case of scrub typhus rapidly presenting with AAH and MODS 2 weeks ago. The clinical data of a 32-year-old female with O. tsutsugamushi-induced AAH and MODS was summarized retrospectively and analyzed with a literature review. In this case, we selected tigecycline and moxifloxacin as treatment regimens for scrub typhus. When the potential infection was controlled, her pancytopenia and hepatic function rapidly improved in a few days.

Spontaneous splenic rupture associated with scrub typhus: a case report

Background Scrub typhus,an acute febrile disease with mild to severe,life-threatening manifestations,potentially presents with a variety of complications,including pneumonia,acute respiratory distress syndrome,cardiac arrhyth-mias(such as atrial fibrillation),myocarditis,shock,peptic ulcer,gastrointestinal bleeding,meningitis,encephalitis,and renal failure.Of the various complications associated with scrub typhus,splenic rupture has rarely been reported,and its mechanisms are unknown.This study reports a case of scrub typhus-related spontaneous splenic rupture and identifies possible mechanisms through the gross and histopathologic findings.Case presentation A 78-year-old man presented to our emergency room with a 5-day history of fever and skin rash.On physical examination,eschar was observed on the left upper abdominal quadrant.The abdomen was not ten-der,and there was no history of trauma.The Orientia tsutsugamushi antibody titer using the indirect immunofluo-rescent antibody test was 1:640.On Day 6 of hospitalization,he complained of sudden-onset left upper abdominal quadrant pain and showed mental changes.His vital signs were a blood pressure of 70/40 mmHg,a heart rate pf 140 beats per min,and a respiratory rate of 20 breaths per min,with a temperature of 36.8℃.There were no signs of gastrointestinal bleeding,such as hematemesis,melena,or hematochezia.Grey Turner's sign was suspected during an abdominal examination.Portable ultrasonography showed retroperitoneal bleeding,so an emergency exploratory laparotomy was performed,leading to a diagnosis of hemoperitoneum due to splenic rupture and a sple-nectomy.The patient had been taking oral doxycycline(1o0 mg twice daily)for 6 days;after surgery,this was dis-continued,and intravenous azithromycin(500 mg daily)was administered.No arrhythmia associated with azithro-mycin was observed.However,renal failure with hemodialysis,persistent hyperbilirubinemia,and multiorgan failure occurred.The patient did not recover and died on the fifty-sixth day of hospitalization.Conclusions Clinicians should consider the possibility of splenic rupture in patients with scrub typhus who display sudden-onset abdominal pain and unstable vital signs.In addition,splenic capsular rupture and extra-capsular hem-orrhage are thought to be caused by splenomegaly and capsular distention resulting from red blood cell congestion in the red pulp destroying the splenic sinus.

Correlation between genotypes of Orientia tsutsugamushi and clinical characteristics of patients with scrub typhus in Guangzhou,China

Objective:To explore the correlation between genotypes of Orientia(O.)tsutsugamushi and clinical characteristics of scrub typhus patients.Methods:Clinical data of patients with scrub typhus admitted to different types of medical institutions in Guangzhou from September 2012 to December 2016 were collected using medical records.Demographic data,clinical manifestations,as well as hematological and biochemical indicators of patients infected with different genotypes were analyzed and compared.Results:A total of 192 patients were included in this study,including 121 patients with Karp genotype of O.tsutsugamushi infection(63.0%),36 patients with Gilliam genotype(19.0%),23 patients with Kato genotype(12.0%),and 12 patients with TA763 genotype(6.0%)infection.The median value of albumin in patients with Karp genotype infection was significantly lower than that of Gilliam-infected patients(P=0.032).Patients with Karp genotype infection had a significantly longer hospital stay(9 days)than those with Gilliam genotype(7 days)(P=0.009)and Kato genotype infection(6 days)(P=0.005).Karp-infected patients also represented for the largest number of patients with complicated organ involvement(88/133,66.2%).Furthermore,Karp-infected patients had higher risk of developing multiple organ dysfunction syndrome(18.2%)and requiring intensive care unit treatment(15.9%).Besides,patients with Gilliam genotype(8 days)and TA763 genotype infection(7.5 days)had shorter fever duration than those with Karp genotype(9 days)and Kato genotype(9 days)infection,respectively.Conclusions:Genotypes of Orientia tsutsugamushi were associated with varying clinical manifestations,organ involvement,and treatment outcomes,suggesting that genotypes ranged in virulence.