• View in gallery
    Figure 1.

    Eschar: a clinical photograph showing an erythematous papule on the right armpit. The scab might have been peeled away.

  • View in gallery
    Figure 2.

    (A) On admission day: bilateral pulmonary infiltration. (B) On hospital day (HD) 2: acute respiratory distress syndrome. (C) On HD 10: improving state. (D) On HD 23: almost recovered by chest radiography. She has been discharged.

  • 1.

    Kelly DJ, Fuerst PA, Ching WM, Richards AL, 2009. Scrub typhus: the geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi. Clin Infect Dis 48: S203S230.

    • Search Google Scholar
    • Export Citation
  • 2.

    Watt G, Parola P, 2003. Scrub typhus and tropical rickettsioses. Curr Opin Infect Dis 16: 429436.

  • 3.

    Peter JV, Sudarsan TI, Prakash JA, Varghese GM, 2015. Severe scrub typhus infection: clinical features, diagnostic challenges and management. World J Crit Care Med 4: 244250.

    • Search Google Scholar
    • Export Citation
  • 4.

    Devine J, 2003. A review of scrub typhus management in 2000–2001 and implications for soldiers. J Rural Remote Environ Health 1: 1420.

    • Search Google Scholar
    • Export Citation
  • 5.

    Vikrant S, Dheer SK, Parashar A, Gupta D, Thakur S, Sharma A, Kaushal SS, Kanga A, 2013. Scrub typhus associated acute kidney injury—a study from a tertiary care hospital from western Himalayan State of India. Ren Fail 35: 13381343.

    • Search Google Scholar
    • Export Citation
  • 6.

    Wang CC, Lai YF, Wong SL, 1999. Adult respiratory distress syndrome caused by scrub typhus—a case report. Thorac Med 14: 8993.

  • 7.

    Wang CC, Liu SF, Liu JW, Chung YH, Su MC, Lin MC, 2007. Acute respiratory distress syndrome in scrub typhus. Am J Trop Med 76: 11481152.

  • 8.

    Sittiwangkul R, Pongprot Y, Silviliarat S, Oberdorfer P, Jittamala P, Sirisanthana V, 2008. Acute fulminant myocarditis in scrub typhus. Ann Trop Paediatr 28: 149154.

    • Search Google Scholar
    • Export Citation
  • 9.

    Chung JH, Lim SC, Yun NR, Shin SH, Kim CM, Kim DM, 2012. Scrub typhus hepatitis confirmed by immunohistochemical staining. World J Gastroenterol 18: 51385141.

    • Search Google Scholar
    • Export Citation
  • 10.

    Kar A, Dhanaraj M, Dedeepiya D, Harikrishna K, 2014. Acute encephalitis syndrome following scrub typhus infection. Indian J Crit Care Med 18: 453455.

    • Search Google Scholar
    • Export Citation
  • 11.

    Arroliga AC, Ghamra ZW, Perez TA, Perez TP, Komara JJ, Smith A, Wiedemann HP, 2002. Incidence of ARDS in an adult population of northeast Ohio. Chest 121: 19721976.

    • Search Google Scholar
    • Export Citation
  • 12.

    Tsay RW, Chang FY, 2002. Acute respiratory distress syndrome in scrub typhus. Q J Med 95: 126128.

  • 13.

    Tseng CC, Tung HH, Wu SF, Wang TJ, 2012. Acute respiratory distress syndrome following scrub typhus: a case report. J Am Acad Nurse Pract 24: 160165.

    • Search Google Scholar
    • Export Citation
  • 14.

    Kim SY, Jang HJ, Kim H, Shin K, Kim MH, Lee K, Kim KU, Park HK, Lee MK, 2014. Patients with acute respiratory distress syndrome caused by scrub typhus: clinical experiences of eight patients. Korean J Crit Care Med 29: 189193.

    • Search Google Scholar
    • Export Citation
  • 15.

    Hemmila MR, Rowe SA, Boules TN, Miskulin J, Mc Gillicuddy JW, Schuerer DJ, Haft JW, Swaniker F, Arbabi S, Hirschl RB, Bartlett RH, 2004. Extracorporeal life support for severe acute respiratory distress syndrome in adults. Ann Surg 240: 595605.

    • Search Google Scholar
    • Export Citation
  • 16.

    Dogra S, 2010. Recent advances in understanding pathophysiology of scrub typhus. JK Science 12: 7071.

  • 17.

    Rapmund G, 1984. Rickettsial diseases of the Far East: new perspectives. J Infect Dis 149: 330338.

  • 18.

    Koh GC, Maude RJ, Paris DH, Newton PN, Blacksell SD, 2010. Diagnosis of scrub typhus. Am J Trop Med Hyg 82: 368370.

  • 19.

    Choi YH, Kim SJ, Lee JY, Pai HJ, Lee KY, Lee YS, 2000. Scrub typhus: radiological and clinical findings. Clin Radiol 55: 140144.

  • 20.

    Song SW, Kim KT, Ku YM, Park SH, Kim YS, Lee DG, Yoon SA, Kim YO, 2004. Clinical role of interstitial pneumonia in patients with scrub typhus: a possible marker of disease severity. J Korean Med Sci 19: 668673.

    • Search Google Scholar
    • Export Citation
  • 21.

    Park JS, Jee YK, Lee KY, Kim KY, Myong NH, Seo PW, 2000. Acute respiratory distress syndrome associated with scrub typhus: diffuse alveolar damage without pulmonary vasculitis. J Korean Med Sci 15: 343345.

    • Search Google Scholar
    • Export Citation
  • 22.

    Tomashefski JF Jr, 2000. Pulmonary pathology of acute respiratory distress syndrome. Clin Chest Med 21: 435466.

  • 23.

    Tseng BY, Yang HH, Liou JH, Chen LK, Hsu YH, 2008. Immunohistochemical study of scrub typhus: a report of two cases. Kaohsiung J Med Sci 24: 9298.

    • Search Google Scholar
    • Export Citation
  • 24.

    Angelakis E, Patrick G, Peloni JM, Wey PF, Perreal C, Raoult D, 2015. Orientia tsutsugamushi in lung of patient with acute respiratory distress syndrome, France, 2013. Emerg Infect Dis 21: 373375.

    • Search Google Scholar
    • Export Citation
  • 25.

    Berman SJ, Kundin WD, 1973. Scrub typhus in Vietnam: a study of 87 cases. Ann Intern Med 79: 2630.

  • 26.

    Brown GW, Saunders JP, Singh S, Huxsoll DL, Shirai A, 1978. Single dose doxycycline therapy for scrub typhus. Trans R Soc Trop Med Hyg 72: 412416.

    • Search Google Scholar
    • Export Citation
  • 27.

    Watt G, Chouriyagune C, Ruangweerayud R, Watcharapichat P, Phulsuksombati D, Jongsakul K, Teja-Isavadharm P, Bhodhidatta D, Corcoran KD, Dasch GA, Strickman D, 1996. Scrub typhus infections poorly responsive to antibiotics in northern Thailand. Lancet 348: 8689.

    • Search Google Scholar
    • Export Citation
  • 28.

    Varghese GM, Trowbridge P, Janardhanan J, Thomas K, Peter JV, Mathews P, Abraham OC, Kavitha ML, 2014. Clinical profile and improving mortality trend of scrub typhus in south India. Int J Infect Dis 23: 3943.

    • Search Google Scholar
    • Export Citation
  • 29.

    Griffith M, Peter JV, Karthik G, Ramakrishna K, Prakash JA, Kalki RC, Varghese GM, Chrispal A, Pichamuthu K, Iyyadurai R, Abraham OC, 2014. Profile of organ dysfunction and predictors of mortality in severe scrub typhus infection requiring intensive care admission. Indian J Crit Care Med 18: 497502.

    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 211 100 5
PDF Downloads 81 37 0
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 

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

Woo Young ChoiDepartment of Internal Medicine, Inha University School of Medicine, Incheon, Korea.

Search for other papers by Woo Young Choi in
Current site
Google Scholar
PubMed
Close
,
Seung Yun LeeDepartment of Internal Medicine, Inha University School of Medicine, Incheon, Korea.

Search for other papers by Seung Yun Lee in
Current site
Google Scholar
PubMed
Close
,
Hea Yoon KwonDepartment of Internal Medicine, Inha University School of Medicine, Incheon, Korea.

Search for other papers by Hea Yoon Kwon in
Current site
Google Scholar
PubMed
Close
,
Jae Hyoung ImDepartment of Internal Medicine, Inha University School of Medicine, Incheon, Korea.

Search for other papers by Jae Hyoung Im in
Current site
Google Scholar
PubMed
Close
,
Areum DureyDepartment of Internal Medicine, Inha University School of Medicine, Incheon, Korea.

Search for other papers by Areum Durey in
Current site
Google Scholar
PubMed
Close
,
Ji Hyeon BaekDepartment of Internal Medicine, Inha University School of Medicine, Incheon, Korea.

Search for other papers by Ji Hyeon Baek in
Current site
Google Scholar
PubMed
Close
,
Young Sam KimDepartment of Thoracic and Cardiovascular Surgery, Inha University School of Medicine, Incheon, Korea.

Search for other papers by Young Sam Kim in
Current site
Google Scholar
PubMed
Close
,
Jae-Seung KangDepartment of Microbiology, Inha University School of Medicine, Incheon, Korea.

Search for other papers by Jae-Seung Kang in
Current site
Google Scholar
PubMed
Close
, and
Jin-Soo LeeDepartment of Internal Medicine, Inha University School of Medicine, Incheon, Korea.

Search for other papers by Jin-Soo Lee in
Current site
Google Scholar
PubMed
Close

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.

Introduction

Scrub typhus, also known as a tsutsugamushi disease, is an acute lethal infectious disease caused by Orientia tsutsugamushi. It is an endemic to a 13,000,000 km2 area of the Asia-Pacific rim, extending from Afghanistan to China, Korea, the islands of the southwestern Pacific, and northern Australia.1 A billion people are at risk, and nearly a million cases are reported each year.2

Scrub typhus is one of the differential diagnosis for fever with thrombocytopenia or hemorrhage.3 Scrub typhus can manifest with either nonspecific febrile illness or constitutional symptoms (fever, rash, myalgia, and headache), or with organ dysfunction, such as the kidney (acute kidney injury), lung (pneumonia), heart (myocarditis), liver (hepatitis), and central nervous system (meningitis).410 Although most patients rapidly improve with appropriate antibiotic therapy, a small percentage of cases experience serious complications.3

Acute respiratory distress syndrome (ARDS) is a serious complication of scrub typhus that occurs when fluid leaks into the alveoli as a result of sepsis. The incidence of ARDS in the general adult population was reported to be 15.3 of 100,000 in Northeast Ohio in 2002.11 The incidence of ARDS in subjects with scrub typhus is much higher than that in general adult population.7,12 Approximately 1–15% of scrub typhus patients also had ARDS.7,13,14

Extracorporeal membrane oxygenation (ECMO) is a therapeutic tool for providing life support to patients with the inability for the lungs or hearts to maintain sufficient oxygenation in the body. ECMO involves placing patients on a vascular circuit with a membrane oxygenator that temporarily takes over the gas exchange function of the lungs. There have been an increasing number of clinical reports documenting the use of ECMO in severe ARDS patients who failed to respond to conventional mechanical ventilation therapy.15 Herein, we describe a case of scrub typhus complicated by ARDS that was successfully managed with ECMO.

Case

A 67-year-old woman was admitted with fever and maculopapular rash on the whole body. She had been a healthy woman without any specific medical history. Three weeks before admission, she had been to a farm and harvested persimmons from a tree in a rural part of Chungcheongnam-do. Thereafter, 4 days before coming to our hospital, she was admitted to a nearby hospital exhibiting signs of fever and skin rash. Paracetamol was given for fever control without much improvement; and when she manifested low blood pressure, she visited our emergency department.

On admission, she was alert, but her physical examination revealed a rash on the whole body with eschar on the right armpit (Figure 1). Her body temperature was 39.6°C, blood pressure was 100/60 mmHg, and pulse rate was 90 beats per minute. Her chest radiography showed bilateral pulmonary infiltration (Figure 2A). The initial arterial blood gas analysis (ABGA) revealed the following: pH, 7.44; PaCO2, 34.2 mmHg; PaO2, 46.1 mmHg; HCO3, 22.9 mmol/L; and oxygen saturation, 84.8%. Her hemoglobin level was 12.6 g/dL, hematocrit was 35.3%, white blood cell count was 10,160/μL, and platelet count was 149,000/μL. Serum blood urea nitrogen and creatinine levels were 28.3 and 0.74 mg/dL, respectively. The total bilirubin level was 0.5 mg/dL; aspartate aminotransferase, 59 IU/L; alanine aminotransferase, 55 IU/L; and alkaline phosphatase, 340 IU/L. Other laboratory tests revealed glucose, 135 mg/dL; C-reactive protein, 16.39 mg/dL; activated partial thromboplastin time, 41.2 seconds; prothrombin time, 13.7 seconds. She was admitted to the intensive care unit, with an oxygen inhaler of 5 L/minute via nasal prong cannular. An indirect fluorescent antibody test for O. tsutsugamushi revealed a titer of 1:1,280.

Figure 1.
Figure 1.

Eschar: a clinical photograph showing an erythematous papule on the right armpit. The scab might have been peeled away.

Citation: The American Society of Tropical Medicine and Hygiene 95, 3; 10.4269/ajtmh.16-0069

Figure 2.
Figure 2.

(A) On admission day: bilateral pulmonary infiltration. (B) On hospital day (HD) 2: acute respiratory distress syndrome. (C) On HD 10: improving state. (D) On HD 23: almost recovered by chest radiography. She has been discharged.

Citation: The American Society of Tropical Medicine and Hygiene 95, 3; 10.4269/ajtmh.16-0069

An intravenous (IV) levofloxacin (750 mg every 24 hour, from hospital day [HD] 1 to HD 13) was administered. Levofloxacin was given for a long time because of severe infection and the possibility of any other coinfection. Doxycycline (100 mg bid, from HD 1 to HD 2 and HD 6 to HD 21) was administered via a Levin tube. An IV azithromycin (500 mg every 24 hour, from HD 2 to HD 4) was administered. Physiologic doses of steroid (hydrocortisone, 200 mg/day) were also administered as an adjuvant therapy for refractory shock.

On HD 2, even with hyperbaric oxygen therapy, oxygen saturation was not maintained (dropped by 50%) and lead to the development of ARDS (Figure 2B); thereafter, she was mechanically ventilated. Despite high ventilator support (fraction of inspired oxygen [FiO2], 1.0), oxygen saturation was only 83%. She was changed to a prone position after 3 hours. A follow-up ABGA revealed an exacerbated pulmonary status: pH, 7.20; PaCO2, 45.0 mmHg; PaO2, 53.0 mmHg; HCO3, 17.6 mmol/L; and oxygen saturation, 78%. The patient was on a continuous mandatory ventilation mode with a tidal volume of 320 mL, respiratory rate of 24/minute, FiO2 of 1.0, and positive end-expiratory pressure of 15 cm H2O (PaO2/FiO2 ratio = 53). Other laboratory results were normal, and urine output was maintained. To deliver sufficient oxygen and to avoid pulmonary oxygen toxicity, veno-venous ECMO was instituted. As a drop of blood pressure was shown after ECMO, a low level of inotropics (norepinephrine, up to 10 μg/minute) was used, which was then tapered out. Fortunately, there was no other organ damage. During the 9th day of ECMO, no complications related to extracorporeal circulation occurred. Throughout the 7th days post initiation of ECMO, radiographic abnormalities and arterial oxygenation progressively improved (Figure 2C). On HD 10, ECMO was discontinued. The ventilator was also weaned off and extubation was done 3 days after the discontinuation of ECMO (on HD 13). She was discharged without sequelae after a total of 23 days in the hospital (Figure 2D).

Discussion

Scrub typhus is a zoonosis caused by O. tsutsugamushi. The reservoirs for infection are the chigger (larva of trombiculid mite) and humans are accidentally infected. It is transmitted by trombiculid mites in long grasses and in dirt-floor homes.

Orientia tsutsugamushi is an obligate intracellular gram-negative bacterium that proliferates within the endothelial cells of small vessels in humans. Systemic vasculitis and perivasculitis are the hallmarks of scrub typhus, which cause increased vascular permeability and hypoperfusion in the tissue.1619 Scrub typhus manifests as either nonspecific febrile illness or multi-organ dysfunction, such as acute kidney injury, ARDS, myocarditis, hepatitis, and meningoencephalitis.410 The involvement of lungs has been described to range from bronchitis and interstitial pneumonitis to ARDS.6,20,21

ARDS is characterized by diffuse pulmonary infiltrates in the X-ray appearance and pathologically by diffuse alveolar damage caused by an insult to the pulmonary capillary endothelium and the alveolar epithelium.22 ARDS is one of the serious complications of scrub typhus, which is associated with high morbidity and mortality.7 Although the pathogenesis of ARDS in scrub typhus is not yet well established, the increase of cytokine due to immunologic response can be suggested.23 Moreover, there has been a reported case where O. tsutsugamushi was cultured from bronchoalveolar lavage.24 With appropriate antibiotics, like doxycycline, serious complications such as ARDS or disseminated intravascular coagulation are rarely seen.25,26 In this case, as our patient did not have any specific medical history, there were no multi-organ failures, except the lung. Despite the administration of doxycycline, 4 days after the onset of fever, ARDS has occurred. The reason is not clear. However, we can consider the following reasons. There is a possibility that a coinfection from another pathogen that we did not detect may have induced ARDS. Another reason less likely could be the infection by doxycycline-resistant strain reported in northern Thailand but there have not been cases reported in Korea.27 The patient in this case had also shown response to doxycycline finally.

In a retrospective study, it was reported that 1.7% of scrub typhus patient had ARDS, and the mortality rate of ARDS was up to 36%.14 As in our case, in spite of the prompt use of antibiotics, the occurrence of ARDS may be inevitable, which can even be fatal. Thus, to improve the prognosis of ARDS, appropriate treatments to sustain an appropriate level of oxygen are important; and ECMO can take such role. In this case, ECMO was a useful bridge for the conventional ventilator therapy. The quick decision to use ECMO was key to shorten the delay of oxygenation.

However, one of the factors to be considered in such a case is the pharmacokinetics of the medications administered. ECMO involves massive influx and efflux of fluids via catheters, which consequently alter the volumes of distribution, elimination of half-lives, and protein bindings of drugs. Furthermore, the inflammatory activation induced by the extracorporeal circulation and exposure of blood to foreign material and the drug sequestration in the circuit both contribute to alteration in antibiotic concentration and half-life. For these reasons, dose requirements may change if ECMO is being instituted. Since patients receiving ECMO commonly face severe infections, correct dosing is of paramount importance to improve survival. Although there are no studies regarding doxycycline and levofloxacin yet, efforts to find the appropriate dose are in progress. Therapeutic drug monitoring (whenever available) or population pharmacokinetics, based on readily available clinical and laboratory data, should help tailor antibiotic dosing to the individual patient.

In recently published large cohort of 623 patients hospitalized with scrub typhus of varying severity from mild to critically ill, the mortality rate was 9%.28 The mortality rate for sicker patients admitted to the intensive care unit with multi-organ failure was 24%.29 Fortunately, the mortality rate is on the decline.3 These observations should encourage clinicians to approach scrub typhus infection with optimism and to provide more aggressive care, such as ECMO.

ACKNOWLEDGMENT

This work was supported by a research grant from Inha University Hospital.

  • 1.

    Kelly DJ, Fuerst PA, Ching WM, Richards AL, 2009. Scrub typhus: the geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi. Clin Infect Dis 48: S203S230.

    • Search Google Scholar
    • Export Citation
  • 2.

    Watt G, Parola P, 2003. Scrub typhus and tropical rickettsioses. Curr Opin Infect Dis 16: 429436.

  • 3.

    Peter JV, Sudarsan TI, Prakash JA, Varghese GM, 2015. Severe scrub typhus infection: clinical features, diagnostic challenges and management. World J Crit Care Med 4: 244250.

    • Search Google Scholar
    • Export Citation
  • 4.

    Devine J, 2003. A review of scrub typhus management in 2000–2001 and implications for soldiers. J Rural Remote Environ Health 1: 1420.

    • Search Google Scholar
    • Export Citation
  • 5.

    Vikrant S, Dheer SK, Parashar A, Gupta D, Thakur S, Sharma A, Kaushal SS, Kanga A, 2013. Scrub typhus associated acute kidney injury—a study from a tertiary care hospital from western Himalayan State of India. Ren Fail 35: 13381343.

    • Search Google Scholar
    • Export Citation
  • 6.

    Wang CC, Lai YF, Wong SL, 1999. Adult respiratory distress syndrome caused by scrub typhus—a case report. Thorac Med 14: 8993.

  • 7.

    Wang CC, Liu SF, Liu JW, Chung YH, Su MC, Lin MC, 2007. Acute respiratory distress syndrome in scrub typhus. Am J Trop Med 76: 11481152.

  • 8.

    Sittiwangkul R, Pongprot Y, Silviliarat S, Oberdorfer P, Jittamala P, Sirisanthana V, 2008. Acute fulminant myocarditis in scrub typhus. Ann Trop Paediatr 28: 149154.

    • Search Google Scholar
    • Export Citation
  • 9.

    Chung JH, Lim SC, Yun NR, Shin SH, Kim CM, Kim DM, 2012. Scrub typhus hepatitis confirmed by immunohistochemical staining. World J Gastroenterol 18: 51385141.

    • Search Google Scholar
    • Export Citation
  • 10.

    Kar A, Dhanaraj M, Dedeepiya D, Harikrishna K, 2014. Acute encephalitis syndrome following scrub typhus infection. Indian J Crit Care Med 18: 453455.

    • Search Google Scholar
    • Export Citation
  • 11.

    Arroliga AC, Ghamra ZW, Perez TA, Perez TP, Komara JJ, Smith A, Wiedemann HP, 2002. Incidence of ARDS in an adult population of northeast Ohio. Chest 121: 19721976.

    • Search Google Scholar
    • Export Citation
  • 12.

    Tsay RW, Chang FY, 2002. Acute respiratory distress syndrome in scrub typhus. Q J Med 95: 126128.

  • 13.

    Tseng CC, Tung HH, Wu SF, Wang TJ, 2012. Acute respiratory distress syndrome following scrub typhus: a case report. J Am Acad Nurse Pract 24: 160165.

    • Search Google Scholar
    • Export Citation
  • 14.

    Kim SY, Jang HJ, Kim H, Shin K, Kim MH, Lee K, Kim KU, Park HK, Lee MK, 2014. Patients with acute respiratory distress syndrome caused by scrub typhus: clinical experiences of eight patients. Korean J Crit Care Med 29: 189193.

    • Search Google Scholar
    • Export Citation
  • 15.

    Hemmila MR, Rowe SA, Boules TN, Miskulin J, Mc Gillicuddy JW, Schuerer DJ, Haft JW, Swaniker F, Arbabi S, Hirschl RB, Bartlett RH, 2004. Extracorporeal life support for severe acute respiratory distress syndrome in adults. Ann Surg 240: 595605.

    • Search Google Scholar
    • Export Citation
  • 16.

    Dogra S, 2010. Recent advances in understanding pathophysiology of scrub typhus. JK Science 12: 7071.

  • 17.

    Rapmund G, 1984. Rickettsial diseases of the Far East: new perspectives. J Infect Dis 149: 330338.

  • 18.

    Koh GC, Maude RJ, Paris DH, Newton PN, Blacksell SD, 2010. Diagnosis of scrub typhus. Am J Trop Med Hyg 82: 368370.

  • 19.

    Choi YH, Kim SJ, Lee JY, Pai HJ, Lee KY, Lee YS, 2000. Scrub typhus: radiological and clinical findings. Clin Radiol 55: 140144.

  • 20.

    Song SW, Kim KT, Ku YM, Park SH, Kim YS, Lee DG, Yoon SA, Kim YO, 2004. Clinical role of interstitial pneumonia in patients with scrub typhus: a possible marker of disease severity. J Korean Med Sci 19: 668673.

    • Search Google Scholar
    • Export Citation
  • 21.

    Park JS, Jee YK, Lee KY, Kim KY, Myong NH, Seo PW, 2000. Acute respiratory distress syndrome associated with scrub typhus: diffuse alveolar damage without pulmonary vasculitis. J Korean Med Sci 15: 343345.

    • Search Google Scholar
    • Export Citation
  • 22.

    Tomashefski JF Jr, 2000. Pulmonary pathology of acute respiratory distress syndrome. Clin Chest Med 21: 435466.

  • 23.

    Tseng BY, Yang HH, Liou JH, Chen LK, Hsu YH, 2008. Immunohistochemical study of scrub typhus: a report of two cases. Kaohsiung J Med Sci 24: 9298.

    • Search Google Scholar
    • Export Citation
  • 24.

    Angelakis E, Patrick G, Peloni JM, Wey PF, Perreal C, Raoult D, 2015. Orientia tsutsugamushi in lung of patient with acute respiratory distress syndrome, France, 2013. Emerg Infect Dis 21: 373375.

    • Search Google Scholar
    • Export Citation
  • 25.

    Berman SJ, Kundin WD, 1973. Scrub typhus in Vietnam: a study of 87 cases. Ann Intern Med 79: 2630.

  • 26.

    Brown GW, Saunders JP, Singh S, Huxsoll DL, Shirai A, 1978. Single dose doxycycline therapy for scrub typhus. Trans R Soc Trop Med Hyg 72: 412416.

    • Search Google Scholar
    • Export Citation
  • 27.

    Watt G, Chouriyagune C, Ruangweerayud R, Watcharapichat P, Phulsuksombati D, Jongsakul K, Teja-Isavadharm P, Bhodhidatta D, Corcoran KD, Dasch GA, Strickman D, 1996. Scrub typhus infections poorly responsive to antibiotics in northern Thailand. Lancet 348: 8689.

    • Search Google Scholar
    • Export Citation
  • 28.

    Varghese GM, Trowbridge P, Janardhanan J, Thomas K, Peter JV, Mathews P, Abraham OC, Kavitha ML, 2014. Clinical profile and improving mortality trend of scrub typhus in south India. Int J Infect Dis 23: 3943.

    • Search Google Scholar
    • Export Citation
  • 29.

    Griffith M, Peter JV, Karthik G, Ramakrishna K, Prakash JA, Kalki RC, Varghese GM, Chrispal A, Pichamuthu K, Iyyadurai R, Abraham OC, 2014. Profile of organ dysfunction and predictors of mortality in severe scrub typhus infection requiring intensive care admission. Indian J Crit Care Med 18: 497502.

    • Search Google Scholar
    • Export Citation

Author Notes

* Address correspondence to Jin-Soo Lee, Division of Infectious Diseases and Infection Control Unit, Department of Internal Medicine, Inha University School of Medicine, 27 Inhang-ro, Jung-gu, Incheon, Korea. E-mail: ljinsoo@inha.ac.kr

Authors' addresses: Woo Young Choi, Seung Yun Lee, Hea Yoon Kwon, Jae Hyoung Im, Areum Durey, Ji Hyeon Baek, Young Sam Kim, and Jin-Soo Lee, Department of Internal Medicine, Inha University Hospital, Incheon, Korea, E-mails: winsomew@naver.com, sylin23@naver.com, haeyoon85@daum.net, dylife83@naver.com, arkim1202@inhauh.com, jhbaek@inha.ac.kr, yskim0922@inhauh.com, and ljinsoo@inha.ac.kr. Jae-Seung Kang, Department of Microbiology, Inha University College of Medicine, Incheon, Korea, E-mail: jaeskang@inha.ac.kr.

Save