[A case of tsutsugamushi disease complicated by multiple organ dysfunction syndrome treated by extracorporeal membrane oxygenation].

Tsutsugamushi disease is an acute infectious disease caused by Rickettsia. Occasionally it has been reported in Macau, China. Critical cases are rare. Because the clinical manifestations of tsutsugamushi disease are non-specific and diverse, if not diagnosed and treated in time, the disease may progress to multiple organ dysfunction syndrome (MODS), severe acute respiratory distress syndrome (ARDS), and even death. A patient with tsutsugamushi disease complicated by MODS was admitted to the intensive care unit (ICU) of Kiang Wu Hospital in Macau, China on September 30, 2021. Combined with the history of outdoor activities (exposure to chigger mite larvae), clinical symptoms and signs (characteristic eschar of tsutsugamushi disease was found on the abdominal skin), related laboratory examinations (Weil-Felix test: negative). Diagnosis of tsutsugamushi disease with MODS. After admission, the patient was treated by anti-infection, correction of coagulation dysfunction, tracheal intubation and mechanical ventilation, noradrenalin to maintain blood pressure, continuous renal replacement therapy (CRRT), but the condition didn't improve significantly. We initiated veno-venous ECMO (VV-ECMO), which was initially setted blood flow to 5 L/min (70 mL×kg-1×min-1), rotate speed to 3 500 rpm, fractional concentration of inspired oxygen (FiO2) to 1.00. Heparin was used as anticoagulant and activated coagulation time (ACT) was kept between 180 and 200 seconds. Meanwhile the speed of fluid removal in CRRT was adjusted. After 9 hours of ECMO support, the oxygenation improved, the blood flow of ECMO was reduced to about 4 L/min (58 mL×kg-1×min-1), rotate speed to 3 000 rpm. The patient's condition improved after 4 days of ECMO treatment and her ECMO flow rate and FiO2 could be decreased gradually. On hospital day 5, ECMO was removed. Eight days on mechanical ventilation, the patient was successfully weaned and extubated. On day 11 of hospitalization, weaned the CRRT and turned to intermittent hemodialysis. The patient was transferred out of ICU due to her stable condition on the 12th day hospitalization. After that, her spontaneous urine output increased gradually. The functions of various organs returned to normal. After 36 days of hospitalization, she recovered and was discharged.

Successful Application of Team Resource Management in Scrub Typhus Infection with Septic Shock.

The fatality rate of scrub typhus infection with septic shock is quite high if timely and correct diagnosis and treatment are not obtained. There are few studies in the literature on the subject of holding TRM conferences to discuss the condition and reach a consensus on treatment. A TRM conference has the significance of early intervention by the medical team and consensus on therapy from the medical doctors and family members. We report the case of scrub typhus infection with septic shock. On the day the patient was hospitalized, the medical team held a TRM conference and invited family members to attend. We found that the eschar on the patient may be related to scrub typhus, which was later confirmed by a positive Weil-Felix test and PCR analysis. Under the consensus treatment, the patient's condition improved considerably within the next day. The most significant difference between the TRM conference and the clinical specialist's consultation is that it can quickly narrow the cognitive gap between doctors and family members and reach a consensus on the patient's therapy strategy, truly avoid medical disputes, and effectively share the stress of attending physician. In this case report, we highlight the significance of the TRM conference.

Prone ventilation in a pregnant patient with scrub typhus-induced acute respiratory distress syndrome.

A 23-year-old primigravida at 20 weeks of gestation presented to our hospital with undifferentiated febrile illness and severe acute respiratory distress syndrome. She was intubated in the emergency department and transferred to the intensive care unit. Initial treatment included ventilatory care, vasopressor support and broad-spectrum antibiotics. Based on a positive PCR assay for scrub typhus, she was treated with intravenous doxycycline and azithromycin. Despite reduction in fever, her oxygenation further declined. Following a risk-benefits assessment, we decided to ventilate her in prone position for 8 hours a day for three consecutive days using a checklist-based protocol. Her oxygenation indices and lung compliance markedly improved over this period, and she was extubated a day later. She was eventually discharged home after 1 week.

Case Report: A Fatal Case of Scrub Typhus Complicated by Heatstroke.

A 76-year-old man who had been bathing in a hot spring was taken to the hospital in a coma. PCR assay performed on the eschar revealed a serotype Hirano/Kuroki of Orientia tsutsugamushi. Coexisted heatstroke superimposed on multiple underlying risk factors likely led to a fatal clinical course.

The Characteristics and Clinical Course of Patients with Scrub Typhus and Queensland Tick Typhus Infection Requiring Intensive Care Unit Admission: A 23-year Case Series from Queensland, Tropical Australia.

Scrub typhus and Queensland tick typhus (QTT)-rickettsial infections endemic to tropical Australia-can cause life-threatening disease. This retrospective study examined the clinical course of all patients with laboratory-confirmed scrub typhus or QTT admitted to the intensive care unit (ICU) of a tertiary referral hospital in tropical Australia between 1997 and 2019. Of the 22 patients, 13 had scrub typhus and nine had QTT. The patients' median (interquartile range [IQR]) age was 50 (38-67) years; 14/22 (64%) had no comorbidity. Patients presented a median (IQR) of seven (5-10) days after symptom onset. Median (IQR) Acute Physiology and Chronic Health Evaluation II scores were 13 (9-17) for scrub typhus and 13 (10-15) for QTT cases (P = 0.61). Following hospital admission, the median (IQR) time to ICU admission was five (2-19) hours. The median (IQR, range) length of ICU stay was 4.4 (2.9-15.9, 0.8-33.8) days. Multi-organ support was required in 11/22 (50%), 5/22 (22%) required only vasopressor support, 2/22 (9%) required only invasive ventilation, and 4/22 (18%) were admitted for monitoring. Patients were ventilated using protective lung strategies, and fluid management was conservative. Standard vasopressors were used, indications for renal replacement therapy were conventional, and blood product usage was restrictive; 9/22 (41%) received corticosteroids. One patient with QTT died, and two (8%) additional patients with QTT developed purpura fulminans requiring digital amputation. Death or permanent disability occurred in 3/9 (33%) QTT and 0/13 scrub typhus cases (P = 0.055). Queensland tick typhus and scrub typhus can cause multi-organ failure requiring ICU care in otherwise well individuals. Queensland tick typhus appears to have a more severe clinical phenotype than previously believed.

Scrub typhus: a reemerging infection.

PURPOSE OF REVIEW: Scrub typhus, caused by Orientia tsutsugamushi, is a widely neglected disease which is gaining global momentum because of its resurgence patterns. The disease is now being reported in newer regions as well as areas previously endemic areas. In this review, we aim to comprehensively review the data available to assist physicians in making an accurate diagnosis and appropriate management of the disease. RECENT FINDINGS: Several diagnostic tests have been developed for confirming scrub typhus. However, there is lack of clarity on which tests are most appropriate in a given clinical scenario. A recent study has demonstrated that in early disease (<7 days) when serological tests remain negative, the quantitative polymerase chain reaction is the most sensitive test. Among the serological tests, both IgM enzyme-linked immunosorbent assay as well as rapid diagnostic tests revealed excellent sensitivities and specificities. SUMMARY: With the reemergence of scrub typhus, a high degree of clinical suspicion is required to appropriately diagnose this disease which presents as an acute febrile illness. It can progress to develop various complications leading to multi-organ dysfunction syndrome. Mild illness responds well to antibiotic treatment with doxycycline and azithromycin. Further studies are required to determine the most optimal therapy in severe scrub typhus infections and superiority of one drug over the other.

Application of Extracorporeal Membrane Oxygenation in Patients with Scrub Typhus Complicated with Acute Respiratory Distress Syndrome.

A 68-year-old woman was diagnosed with scrub typhus and acute pneumonia. Acute respiratory distress syndrome (ARDS) occurred on day 4 after admission and was treated with extracorporeal membrane oxygenation (ECMO). After 7 days of ECMO assistance, her respiratory condition gradually improved, and ECMO was removed. On day 20 after admission, she was discharged without any sequelae. The results suggest that ECMO should be considered as early as possible for patients with ARDS caused by scrub typhus.

Scrub Typhus.

Scrub typhus, also known as tsutsugamushi disease, is caused by Orientia sp. and approximately 1 million new cases are reported annually. This article discusses the importance of scrub typhus and its clinical presentation, diagnosis, treatment, and prevention.

Outcome Predictors in Scrub Typhus Requiring Ventilator and Vasopressor Support.

BACKGROUND: Age and serum creatinine are known to be predictors of mortality in scrub typhus patients admitted in intensive care unit. This study aimed to explore the factors predicting mortality in patients with scrub typhus requiring both ventilator and vasopressor support in our set up. METHODS: A retrospective analysis of 43 patients with scrub typhus (ELISA IgM positive, optical density ?0.5) admitted in Medical Intensive Care unit of Chitwan Medical College Teaching Hospital between April 2016 to September 2017 was performed considering recovery or death (poor outcome) as outcome measurement. Potential variables (p<0.25) from bivariate analysis were used to perform a multivariate logistic regression analysis (p<0.10) to predict mortality. RESULTS: The mortality rate was 56% (24/43). Acute respiratory distress syndrome and shock were observed in all 43 patients. The median (IQR) duration of ventilation use and vasopressor use was 53(101) hours and 48(79.5) hours, respectively. On bivariate analysis, an independent and statistically significant association of mortality with age in years (p=0.039), number of vasopressor use (p<0.001) and serum creatinine more than 1.4 mg/dl (p=0.012) was observed and on multivariate regression analysis, these variables were also the predictors of mortality (age in years: p=0.011, ?=0.115, OR=1.211, 95% CI=1.027-1.225; number of vasopressor use: p=0.009, ?=3.705, OR=40.647, 95% CI=2.532-652.425; serum creatinine more than 1.4 mg/dl: p=0.046, ?=-2.205, OR=0.110, 95% CI=0.013-0.961) Conclusions: In scrub typhus with ARDS and septic shock, increasing age and serum creatinine, and requiring more than one vasopressor to maintain blood pressure are at increased risk of mortality.

Scrub typhus with multi-organ dysfunction syndrome and immune thrombocytopenia: a case report and review of the literature.

BACKGROUND: Scrub typhus is an acute infectious zoonotic disease caused by Orientia tsutsugamushi. Multi-organ dysfunction secondary to scrub typhus is hard to diagnose and has a high mortality rate. Only one case of scrub typhus with multi-organ dysfunction syndrome and immune thrombocytopenia has been reported thus far. In this study, we report a second case of scrub typhus with multi-organ dysfunction syndrome and immune thrombocytopenia, and we summarize its diagnosis and treatment. CASE PRESENTATION: A 43-year-old Han Chinese woman, a sanitation worker, was admitted to our hospital after 7 days of a skin infection and 5 days of a sore throat with fever and dizziness. A physical examination revealed the presence of an eschar on the right side of her neck. She had a history of insect bites during her sanitation work. A diagnostic evaluation identified scrub typhus as the primary illness, which was associated with multi-organ dysfunction syndrome and immune thrombocytopenia. She recovered completely after 15 days of treatment and extensive symptomatic supportive care. CONCLUSION: We report a second case of tsutsugamushi disease with multi-organ dysfunction syndrome and immune thrombocytopenia, which resolved after treatment and extensive care.

Scrub typhus-associated acute kidney injury: A study from a South Indian Tertiary Care Hospital.

Infections including scrub typhus contribute to a significant proportion of community-acquired acute kidney injury (AKI) in the tropics. Scrub typhus infection now requires global attention since disease outbreaks are being reported across continents. We intended to study the clinical profile, renal involvement, and parameters predicting renal involvement in scrub typhus infection. This is a retrospective study. The medical records of all patients who were admitted and treated for scrub typhus infection for a study period of two years (from September 2015 to August 2017) were analyzed, and salient clinical features and laboratory results were collected from the hospital data. Statistical analysis was done from the collected data. Our study had 272 patients including 81 children. Adults constituted 70.96% (n = 193) and the remaining 29.04% (n = 81) were pediatric population. Among adults, females constituted 62.7% (n = 121) and males 37.3% (n = 72). The mean age of the adult population was 45.7 ± 15 years and that of pediatric patients was 8.56 ±5.1 years. 18.7% of adult cases and 3.70% of pediatric cases had AKI. Renal replacement therapy was required in 3.67% of adult cases. Mortality was 4.14% in adults and 1.23% in children. Hypotension, pulmonary involvement, central nervous system involvement, multiorgan dysfunction syndrome, increased total counts, elevated aspartate transaminase levels, and hypoalbuminemia predicted AKI in our adult population. Scrub typhus should be considered as a differential in cases presenting with fever and AKI. Outcomes of scrub typhus infection in terms of mortality seem to be improving in this region.

Risk factors for acquisition of scrub typhus in children admitted to a tertiary centre and its surrounding districts in South India: a case control study.

BACKGROUND: Scrub typhus is a mite borne zoonosis common in the tropics with no good preventive strategy. Children are also affected leading to considerable morbidity and mortality. We conducted a case control study and a vector survey to determine the risk factors for acquisition of scrub typhus. METHODS: A case control study with a 1:2 case control ratio was conducted over a 2 year period at a tertiary care centre and its surrounding districts in South India. Cases were children < 15 years with confirmed scrub typhus. Controls were age and locality matched community controls without fever. Demographic, environmental and behavioural risk factors were obtained in cases and controls by an interview and an environmental survey. A vector survey was also undertaken in the immediate vicinity of the cases. RESULTS: Case Control study: 101 cases and 167 controls were analysed. On multivariate analysis, significant association was observed with environmental factors such as the presence of a water body within 100 m of the house (OR 3.56(1.36,9.75); p 0.011), cooking outside the house (OR 5.61 (1.51,23.01); p 0.011), owning pets (OR 3.33(1.16,9.09); p 0.031), and the presence of bushes within 5 m of the house (OR 2.78 (1.11,7.69); p 0.033). Of the behavioural factors, the child going to school by a vehicle (OR 3.12 (2.29,8.37); p 0.006) was associated with an increased risk. Drying clothes on a clothesline showed a trend towards protection from acquiring scrub typhus (OR 0.31 (0.08, 1.08); p 0.077). Vector survey:26 rodents were trapped in as many houses. Trombiculid mites were isolated in 24 houses with 9(34.6%) being able to transmit scrub typhus. 254 trombiculid mites belonging to four species and two genera were collected. Leptotrombidium deliense, (33.5%). Schoengastiella ligula, (11.0%) of the total mite specimens collected. S. ligula always co-existed with L. deliense. The estimated Chigger index for Leptotrombidium deliense and Schoengastiella ligula was 3.27and 1.08 per animal respectively. CONCLUSIONS: Our study highlights risk factors for scrub typhus, some of which may be modifiable. A clean peri-domestic environment free of vegetation, drying clothes on a clothesline and cooking indoors may decrease the risk of scrub typhus.

The epidemiology and clinical features of rickettsial diseases in North Queensland, Australia: Implications for patient identification and management.

BACKGROUND: Rickettsial infections are a common cause of hospitalization in tropical settings, although early diagnosis is challenging in the rural locations where these infections are usually seen. METHODS: This retrospective, clinical audit of microbiologically-confirmed cases of scrub typhus or spotted fever group (SFG) rickettsial infection between 1997 and 2016 was performed a tertiary referral hospital in tropical Australia. Clinical, laboratory and radiological findings at presentation were correlated with the patients' subsequent clinical course. RESULTS: There were 135 locally-acquired cases (95 scrub typhus, 37 SFG, 3 undifferentiated). There were nine hospitalizations during the first 5 years of the study period and 81 in the last 5 years (p for trend = 0.003). Eighteen (13%) of the 135 cases required ICU admission, all of whom were adults. A greater proportion of patients with SFG infection required ICU support (8/37 (22%) compared with 10/95 (11%) scrub typhus cases), although this difference did not reach statistical significance (p = 0.10). Three (8%) of the 37 patients with SFG infection had severe disease (1 died, 2 developed permanent disability) versus 0/95 scrub typhus patients (p = 0.02). Adults with a high admission qSOFA score (≥2) had an odds ratio (OR) of 19 (95% CI:4.8-74.5) for subsequent ICU admission (p<0.001); adults with a high NEWS2 score (≥7) had an OR of 14.3 (95% CI:4.5-45.32) for ICU admission (p<0.001). A patient's respiratory rate at presentation had strong prognostic utility: if an adult had an admission respiratory rate <22 breaths/minute, the negative predictive value for subsequent ICU admission was 95% (95% CI 88-99). CONCLUSIONS: In the well-resourced Australian health system outcomes are excellent, but the local burden of rickettsial disease appears to be increasing and the clinical phenotype of SFG infections may be more severe than previously believed. Simple, clinical assessment on admission has prognostic utility and may be used to guide management.

The reliability of the clinical examination in predicting hemodynamic status in acute febrile illness in a tropical, resource-limited setting.

Introduction: The clinical examination alone is widely considered unreliable when assessing fluid responsiveness in critically ill patients. Little evidence exists on the performance of the clinical examination to predict other hemodynamic derangements or more complex hemodynamic states. Materials and methods: Patients with acute febrile illness were assessed on admission, both clinically and per non-invasive hemodynamic measurement. Correlations between clinical signs and hemodynamics patterns were analyzed, and the predictive capacity of the clinical signs was examined. Results: Seventy-one patients were included; the most common diagnoses were bacterial sepsis, scrub typhus and dengue infection. Correlations between clinical signs and hemodynamic parameters were only statistically significant for Cardiac Index (r=0.75, p-value <0.01), Systemic Vascular Resistance Index (r=0.79, p-value <0.01) and flow time corrected (r=0.44, p-value 0.03). When assessing the predictive accuracy of clinical signs, the model identified only 62% of hemodynamic states correctly, even less if there was more than one hemodynamic abnormality. Discussion: The clinical examination is not reliable to assess a patient's hemodynamic status in acute febrile illness. Fluid responsiveness, cardiodepression and more complex hemodynamic states are particularly easily missed.

Differential diagnosis of scrub typhus meningitis from tuberculous meningitis using clinical and laboratory features.

OBJECTIVES: The involvement of the central nervous system in the form of meningitis or meningoencephalitis is common in scrub typhus and is an important differential diagnosis of other lymphocytic meningitis like tuberculous meningitis (TBM). The aim of this study was to identify the clinical and laboratory parameters that may be helpful in differentiating scrub typhus meningitis from TBM. PATIENTS AND METHODS: We compared of the clinical and laboratory features of 57 patients admitted with scrub typhus meningitis or TBM during a 3-year period. Patients who had abnormal cerebrospinal fluid (CSF) and positive scrub typhus enzyme-linked immunosorbent assay serology (n=28) were included in the scrub typhus meningitis group, while the TBM group included those who satisfied the consensus diagnostic criteria of TBM (n=29). RESULTS: Compared with the TBM group, the mean duration of symptoms was less in patients with scrub typhus meningitis, who also had a lower magnitude of neurological deficits, such as altered mental status and cranial nerve and motor deficits. Patients with scrub typhus meningitis had a lower CSF white blood-cell count (WBC) than the TBM group (130.8±213 195±175 cells/mm3, P=0.002), lower CSF protein elevation (125±120 vs. 195.2±108.2mg/dl, P=0.002), and higher CSF sugar (70.1±32.4 vs. 48.7±23.4mg/dl, P=0.006). Features predictive of the diagnosis of scrub typhus meningitis included the absence of neurological impairment at presentation, blood serum glutamic-oxaloacetic transaminase>40 international units (IU)/L, serum glutamic-pyruvic transaminase>60 IU/L, total blood leukocyte count>10,000/mm3, CSF protein<100mg/dl, CSF sugar>50mg/dl, CSF WBC<100 cells/mm3. All patients with scrub typhus meningitis recovered completely following doxycycline therapy CONCLUSIONS: This study suggests that, clinical features, including duration of fever, neurological deficits at presentation and laboratory parameters such as CSF pleocytosis,CSF protein elevation, CSF sugar levels and liver enzyme values are helpful in differentiating scrub typhus meningitis from tuberculous meningits. These features with scrub IgM serology may be helpful in identifying patients with scrub meningitis and in avoiding prolonged empirical antituberculous therapy in cases of lymphocytic meningitis.

Successfully Managed Acute Transverse Myelitis Related to Scrub Typhus and Serial Image Findings.

Central nervous system involvement manifesting as meningitis or meningoencephalitis is a known complication of scrub typhus, but very few spinal cord lesions such as acute transverse myelitis (ATM) have been reported in association with this disease. Scrub typhus patients with a spinal lesion present with neurologic symptoms including dysuria, motor, and sensory weakness. Herein, we describe a rare case of ATM associated with scrub typhus. Clinical characteristics, cerebrospinal fluid cytology, Orientia tsutsugamushi serum antibody titer, and serial magnetic resonance imaging scans resulted in a diagnosis of ATM associated with scrub typhus.

Protective and Pathogenic Roles of CD8+ T Lymphocytes in Murine Orientia tsutsugamushi Infection.

T cells are known to contribute to immune protection against scrub typhus, a potentially fatal infection caused by the obligate intracellular bacterium Orientia (O.) tsutsugamushi. However, the contribution of CD8+ T cells to protection and pathogenesis during O. tsutsugamushi infection is still unknown. Using our recently developed BALB/c mouse model that is based on footpad inoculation of the human-pathogenic Karp strain, we show that activated CD8+ T cells infiltrate spleen and lung during the third week of infection. Depletion of CD8+ T cells with monoclonal antibodies resulted in uncontrolled pathogen growth and mortality. Adoptive transfer of CD8+ T cells from infected animals protected naïve BALB/c mice from lethal outcome of intraperitoneal challenge. In C57Bl/6 mice, the pulmonary lymphocyte compartment showed an increased percentage of CD8+ T cells for at least 135 days post O. tsutsugamushi infection. Depletion of CD8+ T cells at 84 days post infection caused reactivation of bacterial growth. In CD8+ T cell-deficient beta 2-microglobulin knockout mice, bacterial replication was uncontrolled, and all mice succumbed to the infection, despite higher serum IFN-γ levels and stronger macrophage responses in liver and lung. Moreover, we show that CD8+ T cells but not NKT cells were required for hepatocyte injury: elevated concentrations of serum alanine aminotransferase and infection-induced subcapsular necrotic liver lesions surrounded by macrophages were found in C57Bl/6 and CD1d-deficient mice, but not in beta 2-microglobulin knockout mice. In the lungs, peribronchial macrophage infiltrations also depended on CD8+ T cells. In summary, our results demonstrate that CD8+ T cells restrict growth of O. tsutsugamushi during acute and persistent infection, and are required to protect from lethal infections in BALB/c and C57BL/6 mice. However, they also elicit specific pathologic tissue lesions in liver and lung.

A Case of Scrub Typhus Complicated by Adult Respiratory Distress Syndrome and Successful Management with Extracorporeal Membrane Oxygenation.

A 67-year-old woman was diagnosed as having scrub typhus with pneumonitis. On admission, she was started on a combination therapy with levofloxacin and doxycycline. However, the patient developed severe acute respiratory distress syndrome (ARDS) on the 2nd day, and as a result, she underwent extracorporeal membrane oxygenation (ECMO). She was weaned from ECMO on the 10th day, as her respiratory status gradually improved. She was discharged without sequelae on the 23rd day. The outcome suggests that the use of ECMO should be considered for patients with ARDS induced from scrub typhus.

Acute Cholecystitis in Patients with Scrub Typhus.

Acute cholecystitis is a rare complication of scrub typhus. Although a few such cases have been reported in patients with scrub typhus, the clinical course is not well described. Of 12 patients, acute cholecystitis developed in 66.7% (8/12) of patients older than 60 yr. The scrub typhus group with acute cholecystitis had marginal significant longer hospital stay and higher cost than the group without cholecystitis according to propensity score matching. Scrub typhus should be kept in mind as a rare etiology of acute cholecystitis in endemic areas because the typical signs of scrub typhus such as skin rash and eschar can present after the abdominal pain.