Scrub typhus is an acute, febrile zoonosis, caused by an obligate intracellular bacterium Orientia tsutsugamushi (O tsutsugamushi). The disease is of greatest public health importance in rural areas of Asia and in Western Pacific Islands. The clinical manifestations of the disease range from sub-clinical disease to an organ failure. The various complications known with this disease are jaundice, renal failure, pneumonitis, acute respiratory distress syndrome (ARDS), septic shock, myocarditis and meningo-encephalitis. The complications of scrub typhus usually develop after the 1 st week of illness. We report a 60-year-old farmer with scrub typhus, who presented with multi-organ dysfunction and recovered completely with treatment.
Keywords: Eschar, meningo-encephalitis, Orientia tsutsugamushi, renal failure, weil felix test
|How to cite this article:
Subbanna PA, Suri SD. Multi-organ dysfunction in scrub typhus. Ann Trop Med Public Health 2012;5:393-6
Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi shi (O tsutsugamushi) and is transmitted to humans by the bite of a larval-stage trombiculid mite or chigger. It is an important consideration in the differential diagnosis of an acute febrile illness.  The incubation period varies from 6-21 days. The common symptoms are fever, chills, headache, myalgia, dry cough, lymphadenopathy and gastrointestinal disturbances.  The eschar is the pathognomonic sign of scrub typhus and was seen in less than 10% of cases in the Indian subcontinent.  Therefore, in the absence of eschar, it is difficult to distinguish scrub typhus clinically from other common acute febrile illness like typhoid, leptospirosis, malaria and dengue fever. The delay in diagnosis and treatment of scrub typhus results in the development of complications, which is usually seen in the 2 nd week of illness. We report a case of scrub typhus, presented with multi-organ dysfunction in the 1 st week of illness that recovered completely with timely diagnosis and management.
A 60-year-old farmer presented with 7 days history of high-grade fever with chills, rigors, headache and 2 days history of severe dry cough with an altered sensorium. There was no history of vomiting, ear discharge, seizures, photophobia or weakness of any limb. Examination revealed temperature of 39°C, icterus and eschar around 1 cm in size on the lateral aspect of the right lower chest [Figure 1]. His respiratory rate was 24/min, pulse rate 98/min, and blood pressure was 80/50 mmHg. Respiratory system examination revealed coarse crepitation in the right infrascapular and axillary area. Central nervous system examination (CNS) revealed no focal neurological deficit, but there was terminal neck rigidity. Cardiovascular system and abdomen examination was normal. Laboratory investigations revealed an altered renal and liver function tests [Table 1]. Complete blood picture revealed a normal total and platelet count, and there were no malarial parasites in the peripheral smear. The chest x-ray showed reticular infiltration of the right lower zone of the lung [Figure 2]a, and 2 days later, chest x-ray showed bilateral infiltration of the lung zones [Figure 2]b. The cerebrospinal fluid (CSF) analysis revealed protein of 80 mg/dl; sugar of 60 mg/ dl, 150 lymphocytes and grams stain was negative. The electrocardiogram, echocardiogram and ultrasound abdomen were normal. The blood culture, urine culture and CSF culture were sterile. The WIDAL, leptospira and dengue serology were negative.
||Figure 2: Chest X-ray (a) shows infiltrates in the right lower zone of lung and (b) shows diffuse infiltration of both lung fields
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Patient presented to our emergency medical services department with fever, eschar, pneumonitis, shock, jaundice and features of meningo-encephalitis. His arterial blood gas analysis showed respiratory alkalosis with oxygen saturation (Spo2) of 72 mmHg and central venous pressure (CVP) of 4 cms of H20. He was initially resuscitated with intravenous fluids for correction of low CVP, but in view of persistent shock, he was started on an inotropic support. He also received doxycycline treatment (100 BID orally). On day 2 of hospital admission, he developed ARDS and required mechanical ventilator support for 5 days in an intensive care unit. In view of clinical deterioatition in hospital, he received azithromycin (500 mg intravenous OD for 7 days). On day 3 of hospital admission, his blood pressure improved and he was weaned off from an inotropic support. He became afebrile after 72 hours of treatment, and his symptoms completely resolved in 6 days, and weaned off from mechanical ventilator support on day 6 of hospital admission. His repeat chest x-ray on day 8 showed cleared infiltrates with minimal right pleural effusion [Figure 3]. He also had renal and hepatic dysfunction, which was managed symptomatically.
||Figure 3: Chest X-ray showing cleared infiltrates before discharge with minimal right pleural effusion
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The target cells for O tsutsugamushi are endothelial cells and macrophages. It disseminates into the multiple organs through endothelial cells via hematogenous and lymphogenous routes and predominantly locates in the macrophages of the liver and spleen.  The bacteria then cause focal or systemic vasculitis and perivasculitis in multiple organs, with various complications. The complications of scrub typhus usually develop after the 1 st week of untreated illness. The various complications known to occur with this disease are acute renal failure, acute hepatic failure, interstitial pneumonitis, ARDS, septic shock, myocarditis, pericarditis, meningo-encephalitis, and also acute hearing loss is reported. , The various risk factors for the severity of infection include older age, male gender, potentially hemolytic conditions, such as glucose-6-phosphate dehydrogenase deficiency and treatment with a sulfonamide-containing antimicrobial drug.  The pulmonary manifestations described in scrub typhus include, varying grades of bronchitis and interstitial pneumonitis, progressing to ARDS.  A cough, with or without infiltrates on the chest radiograph, is one of the common presentations of the scrub typhus.  ARDS is very rare, but a serious complication of scrub typhus. The pathogenesis involves vasculitis of the pulmonary vessels by direct invasion by O. tsutsugamushi.
The CNS manifestations in scrub typhus vary from aseptic meningitis to meningo-encephalitis. It present with confusion, delirium and may develop seizures. Focal neurological signs are rare, but are known to occur. Cerebrospinal fluid profile may show changes similar to viral or tuberculous meningitis.  Hepatic injury in scrub typhus is usually mild. Liver involvement with jaundice and abnormal liver function test may result from sinusoidal infiltration, pericholangitis, and perivascular lesion in the portal area of the liver. An acute renal failure is rare in scrub typhus, and proposed mechanisms include prerenal azotemia resulting from hypotension and volume depletion.  It can be a part of DIC, and there are reports of an acute tubular necrosis due to the direct invasion of O. tsutsugamushi.  The prerenal azotemia also results from the decreased renal perfusion due to an increased vascular permeability resulting from systemic vasculitis. 
The Weil-Felix test (WFT) is most common and commercially available test for the diagnosis of scrub typhus in developing countries like India. The sensitivity and specificity of the WFT is low and is usually positive during the 2 nd week of illness. The gold standard confirmatory tests are the indirect immunoperoxidase test and the immunofluorescent assay (IFA). These tests are costly and not easily available in developing countries like India. Therefore, the diagnosis of scrub typhus is mainly by clinical suspicion and by characteristic clinical finding, eschar. Therefore, thorough search for eschar over all the areas of body is very important in the clinical examination of all acute febrile illnesses.
The preferred drugs in the treatment include doxycycline and chloramphenicol. Doxycycline is usually given as 100 mg PO twice daily for 7 to 14 days. The alternative drugs used in scrub typhus include rifampin (600 to 900 mg/day) and azithromycin. An early treatment shows better outcomes and faster resolution than the delayed treatment; and delayed administration of antibiotics is independently associated with major organ dysfunction.  Patients treated with appropriate antibiotics typically become afebrile within 48 hours of therapy.
Our case presented with MODS and in hospital developed ARDS, which is rare complication. The risk factors for severity of illness in our patient are an older age (60 years) and male gender. He received treatment with both doxycycline and azithromycin along with the supportive management, and he recovered completely over a period of 8 days. The presentation with complications in the 1 st week of illness is very unusual in our case.
In conclusion, the complications of scrub typhus can occur in 1 st week of illness and severity range from a mild illness to myriad of life threatening events. The delay in diagnosis and treatment can result in the development of many complications and hence early diagnosis and treatment is important in reducing the mortality and morbidity. In developing countries, where scrub typhus is endemic, the need for the development of rapid high sensitive and commercially available diagnostic tests is very important. And also, the treatment of all acute febrile illness with empirical doxycycline can be considered pending diagnosis, especially in endemic areas.
||Watt G, Parola P. Scrub typhus and tropical rickettsioses. Curr Opin Infect Dis 2003;16:429-36.
||Mathai E, Rolain JM, Verghese GM, Abraham OC, Mathai D, Mathai M, et al. Outbreak of scrub typhus in Southern India during the cooler months. Ann N Y Acad Sci 2003;990:359-64.
||Varghese GM, Abraham OC, Mathai D, Thomas K, Aaron R, Kavitha ML, et al. Scrub typhus among hospitalised patients with febrile illness in South India: Magnitude and clinical predictors. J Infect 2006;52:56- 60.
||Moron CG, Popov VL, Feng HM, Wear D, Walker DH. Identification of the target cells of Orientia tsutsugamushi in human cases of scrub typhus. Mod Pathol 2001;14:752-9.
||Cracco C, Delafosse C, Baril L, Lefort Y, Morelot C, Derenne JP, et al. Multiple organ failure complicating probable scrub typhus. Clin Infect Dis 2000;31:191-2.
||Premaratna R, Chandrasena TG, Dassayake AS, Loftis AD, Dasch GA, de Silva HJ. Acute hearing loss due to scrub typhus: A forgotten complication of a reemerging disease. Clin Infect Dis 2006;42:e6-8.
||David H. Walker. Rickettsial diseases in travelers. Travel Med Infect Dis 2003;1:35-40.
||Chayakul P, Panich V, Silpapojakul K. Scrub typhus pneumonitis: An entity, which is frequently missed. Q J Med 1988;68:595-602.
||Tsay RW, Chang FY. Acute respiratory distress syndrome in scrub typhus. Q J Med 2002;95:126-8.
||Kim DM, Kang DW, Kim JO, Chung JH, Kim HL, Park CY, et al. Acute Renal Failure Due to Acute Tubular Necrosis Caused by Direct Invasion of Orientia tsutsugamushi. J Clin Microbiol 2008;46:1548-50.
||Dumler JS, Taylor JP, Walker DH. Clinical and laboratory features of murine typhus in south Texas. JAMA 1991;266:1365-70.
||Lee N, Ip M, Wong B, Lui G, Tsang OT, Lai JY, et al. Risk factors associated with life-threatening rickettsial infections. Am J Trop Med Hyg 2008;78:973-8.
Source of Support: None, Conflict of Interest: None
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