Background: Scrub typhus was unseen in Odisha, but during postmonsoon months of 2014, for the first time, 25 cases of scrub typhus were identified in the pediatric department of Kalinga Institute of Medical Sciences, Bhubaneswar. Objectives: This study aimed at analyzing the demographic pattern, symptomatology, complications, and response to therapy, which will help medical fraternity in early diagnosis and management. Materials and Methods: By retrospective analysis of case records between September 2014 and February 2015, 25 children were found to have scrub typhus by the detection of specific IgM by enzyme-linked immunosorbent assay (ELISA) method. Results: Main clinical manifestations were prolonged fever (100%), respiratory distress (44%), shock, hepatomegaly (96%), splenomegaly (68%), lymphadenopathy (24%), and third spacing (40%). The characteristic eschar was found in 48% children (n = 12). Laboratory findings were leukocytosis (44%), thrombocytopenia (24%), raised C-reactive protein (96%), and transaminitis (76%). All cases were found to be positive for specific IgM by ELISA method (100%). Complications detected were myocarditis (28%), encephalopathy (12%), acute respiratory distress syndrome (4%), and multiorgan dysfunction. Twenty-four cases received doxycycline and all improved, whereas one child who did not get doxycycline expired (died within 24 h of hospitalization). Discussion: Vasculitis is the basic pathogenic mechanism in scrub typhus. An eschar is the most characteristic and pathognomonic feature of scrub typhus but not seen in all patients. If a combination of elevated transaminases, leukocytosis, and thrombocytopenia is found, then specificity and positive predictive value for diagnosis are about 80%. Doxycycline is the drug of choice. Conclusion: Pediatricians and physicians must be aware of scrub typhus for early diagnosis and treatment of this emerging disease.
Keywords: Doxycycline, eschar, myocarditis, rickettsial disease, scrub IGM by ELISA,
|How to cite this article:
Patnaik S, Swain N, Sahoo B, Mishra R, Jain MK. Emergence of scrub typhus in Odisha – A hospital based study. Ann Trop Med Public Health 2017;10:636-40
|How to cite this URL:
Patnaik S, Swain N, Sahoo B, Mishra R, Jain MK. Emergence of scrub typhus in Odisha – A hospital based study. Ann Trop Med Public Health [serial online] 2017 [cited 2020 Aug 3];10:636-40. Available from: https://www.atmph.org/text.asp?2017/10/3/636/213125
Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi, an obligate intracellular Gram-negative bacterium. It is a zoonotic disease transmitted by larval mites (chiggers) of Leptotrombidium deliense group. Human is accidentally infected when he/she encroaches the mite infested area, known as mite islands. The term scrub was used because of the type of vegetation (terrain between woods and clearings) that harbors the vector mite. Although the disease is known to be prevalent in jungle areas, it can affect diverse habitats such as seashore, rice fields, and even semi-deserts. Rickettsial disease was not heard of in Odisha till now, but detection of 25 cases in the postmonsoon months of 2014 at our institute left all pediatricians off guard. Many cases with organ(s) failure were received from other hospitals and were diagnosed and successfully treated. Hence, this study has been carried out retrospectively to analyze symptomatology, possible complications, and treatment strategy, which would help sensitize the local medical fraternity for proper management of this new disease.
|Materials and Methods|
We did retrospective analysis of case records of all children diagnosed to have scrub typhus between September 2014 and February 2015 in department of pediatrics of Kalinga Institute of Medical Sciences, a tertiary care and teaching hospital in Bhubaneswar. Data including demography, clinical manifestations, and investigation reports were recorded. Scrub typhus cases were diagnosed by detection of IgM antibody to 56 kDa antigen by enzyme-linked immunosorbent assay (ELISA) technique (InBiOS International Inc., USA).
A total of 25 children were diagnosed with scrub typhus from September 2014 to February 2015 [Table 1]. The youngest patient was a 1-year-old child, while oldest one was of 12 years. Sixty percent of children (n = 15) were girls, while 40% (n = 10) were boys. All presented with high-grade fever. Of 25 children, 22 (88%) had fever for more than 1 week, while 3 (12%) had fever period of <1 week. Cases were detected from many districts of Odisha. We found seven cases from Bhubaneswar city, eight cases from Dhenkanal district, four from Khurda district, two from Keonjhar, and one each from Balasore, Kendrapara, Jharsuguda, and Debgarh district.
|Table 1: Clinical manifestations and investigations in scrub typhus cases
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Respiratory distress was the presenting symptom in 44% (n = 11) children. 32% (n = 8) children presented with shock. Altered sensorium was found in six children (24%), of whom two (8%) had seizures at presentation. Ninety-two percent children (n = 23) had hepatomegaly, while splenomegaly detected in 68% (n = 17) of children. Lymphadenopathy was found in 24% (n = 6) children, while two had tender lymphadenopathy (8%). Edema of hands and legs was found in 40% children (n = 10). Two children (8%) had oliguria and both responded to conservative management. Evidence of myocarditis was detected in 28% children (n = 7). Abdominal pain was found in 40% of children (n = 10).
The characteristic eschar was found in 48% of children (n = 12). The sites included neck, axilla, abdomen, behind ear, inside tragus, groin, prepuce, vulva, and scrotum [Figure 1] and [Figure 2]. In almost all, eschar was detected in covered or hidden parts of the body. Leukocytosis (<12,000) was detected in 44% (n = 11) of patients and 8% (n = 2) had total leukocyte count more than 20000. Neutrophilia (neutrophil count >70%) was detected in 36% (n = 9) children. Twenty-four percent patients had thrombocytopenia (n = 6), of whom three had platelet clumps. Serum urea and creatinine were elevated in one patient (4%) and she responded to medical management.
|Figure 1: Eschar in the ear
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|Figure 2: Eschar in the vulva
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C-reactive protein level was elevated in 96% (n = 24) children. Alanine aminotransferase (ALT) level was elevated in 48% (n = 12) and aspartate aminotransferase (AST) in 76% (n = 19). Serum albumin level was found to be low in 88% (n = 22) children.
Abnormal chest X-ray was found in 40% patients. One child had features of acute respiratory distress syndrome (ARDS).
All children were found to have scrub IgM positive by ELISA method.
Of the series of 25 children, 24 (96%) improved while one child expired (4%). He had myocarditis and died within 24 h of hospitalization. 80% (n = 20) children showed response to doxycycline within 48 h of starting. 100% children improved with doxycycline while the child who expired had not received doxycycline (died within 24 h of hospitalization).
All cases in our series presented with fever. This is a universal symptom in all cases. None of the patients gave a history of mite bite. This may be due to small size of mite and the fact that the bite does not cause pain or itching. The incubation period of O. tsutsugamushi in humans is 10–12 days. The clinical manifestations vary from mild febrile illness to a severe potentially fatal disease with multiple organ dysfunction syndrome (MODS). Vasculitis is the basic pathogenic mechanism in scrub typhus. It is responsible for skin rash, microvascular leakage, edema, tissue hypoperfusion, and end-organ ischemic injury.
An eschar is the most characteristic and pathognomonic feature of scrub typhus, but not seen in all patients. Eschar is a black necrotic lesion resembling a cigarette burn, usually found in areas where skin is thin, moist, and wrinkled. It starts as a small papule that enlarges and subsequently undergoes central necrosis to turn black. Eschar is not easily detectable until the scab falls off, after 10–12 days, leaving a crater with yellow base. Early stages of eschar frequently go unnoticed in dark-skinned people. In our series, eschar was found in 48% of children (n = 12). Different Indian studies of the last 6 years have reported eschar from 12.5% to 35% [Table 2] and [Table 3].,,,,,,
|Table 2: Clinical manifestations as per the recent studies of the last 6 years
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|Table 3: Investigation findings in scrub typhus cases in recent studies
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Twelve percent of children in our study had maculopapular rash, while other Indian studies have reported rashes ranging from 14% to 53%.,,,,,, Mathai et al. had found maculopapular rashes in all of her patients (100%).
Puffiness of face and edema was found in 40% children (n = 10). Our findings are comparable to the findings of other Indian studies.,, We found hepatomegaly and splenomegaly in 92% and 68% children, respectively. It matches with the findings of other studies.,,,,,, Lymphadenopathy was observed in 24% (n = 6) children. Kawoosa et al. and Vivekanandan et al. had found lymphadenopathy in 95% and 30% cases, respectively., In a recent study from Dehradun, tender lymphadenopathy was detected in 38% cases. We found tender lymphadenopathy only in two children (8%).
Leukocytosis was found in 44% cases, and it is almost similar to other studies which ranges from 49% to 67%.,,,,,, Thrombocytopenia was detected in 24% children (n = 6). Other studies from the recent past have found low platelets in 25%–77% of patients.,,,,,,
Among laboratory parameters, we found elevated transaminases (ALT and AST) in 48% and 76%, respectively. Subbalaxmi et al. had found transaminitis in 100% of their cases, while in other studies, it ranges from 33% to 96%.,,,,,, C-reactive protein level was elevated in 96% (n = 24) cases in our series. Similar results are found in studies from Jammu and Chennai., If a combination of elevated transaminases, leukocytosis, and thrombocytopenia is used, the specificity and positive predictive value for diagnosis of scrub typhus are about 80%.,
From, the 2nd week onward, a proportion of patients (especially those with untreated disease) will show evidence of systemic infection. This stage of illness can attack different organ systems such as central nervous system (acute diffuse encephalomyelitis, encephalopathy, meningitis, deafness, cranial nerve palsies), cardiovascular system (arrhythmia, myocarditis, congestive heart failure, and vasculitis), renal system (acute renal failure), respiratory system (interstitial pneumonia, ARDS), and gastrointestinal system (liver function derangement, pancreatitis, diarrhea). Sometimes, MODS ensues. Due to wide variation in clinical manifestations, the diagnosis of scrub typhus is often missed or made late.
Evidence of myocarditis in the form of abnormal ECG and elevated creatinine kinase-MB level was found in seven children (28%). The study from Dehradun has found myocarditis in 9% cases. The child, who succumbed in our study group, had features of myocarditis. ARDS-like manifestation was found in one child (4%) and he responded to doxycycline and noninvasive ventilation (bilevel positive airway pressure). Palanivel et al. and Vivekanandan et al. have found ARDS in 4% and 8% cases, respectively., Features of meningoencephalitis were detected in three children (12%). A study from Taiwan found encephalitis in 21% cases.
The Weil-Felix test is the widely used test, but it has low sensitivity and specificity. The specific gold standard test for scrub typhus is microimmunofluorescence test, namely, indirect immunofluorescence assay.,, Diagnosis was established in our study by detection of scrub IgM by ELISA technique. All of our patients had scrub IgM positive by ELISA method. It has a sensitivity of about 85%, and above all, this test is very simple. In the test kit, wells of each plate have been coated with recombinant antigen mix. During testing, the serum samples are diluted and applied to each well. After incubation and washing, the wells are treated with polyclonal goat anti-human IgM antibodies labeled with enzyme horseradish peroxidase. After a second incubation and washing step, the wells are incubated with trimethylbenzidine substrate. An acidic stopping solution is then added, and the degree of enzymatic turnover of the substrate is determined by absorbance measurement at 450 nm. The absorbance measured is directly proportional to the concentration of IgM antibodies to O. tsutsugamushi.
Doxycycline is the drug of choice. The recommended treatment duration is 7–14 days. Treatment less than 1 week is initially curative but may be followed by relapse. In case of children, azithromycin can be used. It has been shown to have comparable efficacy when compared to doxycycline in a small trial. All patients in our series showed a remarkable response to doxycycline and 92% became afebrile within 48 h. This rapid response to doxycycline is so characteristic that it can be used as a therapeutic test., Mortality rate in our study group was 4% and other studies have also similar results.,
Outdoor activities in areas with high uncut grass, weeds, low bushes, or animal sheds where ticks are often seen is a definite risk factor for transmission of scrub typhus. It is important to have proper differential diagnosis of fever cases in regions where several infections such as malaria, pneumonia, dengue, and scrub are common. Exact diagnosis is important as a specific medication is required for specific disease, and it can prevent mortality and morbidity. Unnecessary use of higher antibiotics is not at all helpful in scrub typhus.
The emergence of scrub typhus in Odisha demands a high degree of clinical suspicion, familiarity with the various clinical manifestations, and availability and use of rapid immunological tests in suspected cases to allow early diagnosis and timely initiation of appropriate therapy. It has to be considered in the differential diagnosis of prolonged fever, sepsis, and MODS. All out efforts are to be made for detection of an eschar in hidden areas of the body, but its absence does not rule out the disease.
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Mahajan SK. Scrub typhus. J Assoc Physicians India 2005;53:954-8.
Rajapakse S, Rodrigo C, Fernando D. Scrub typhus: Pathophysiology, clinical manifestations and prognosis. Asian Pac J Trop Med 2012;5:261-4.
Rathi N, Rathi A. Rickettsial infections: Indian perspective. Indian Pediatr 2010;47:157-64
Kawoosa Z, Kundal V, Hamid S, Kawoosa N, Gupta BB, Kundal S et al. Clinical profile of Rickettsial disease in Jammu (Northern India). Int J Trop Med Public Health 2012;1:1-31.
Krishna MR, Vasuki B, Nagaraju K. Scrub typhus: Audit of an outbreak. Indian J Pediatr 2015;82:537-40.
Kumar Bhat N, Dhar M, Mittal G, Shirazi N, Rawat A, Prakash Kalra B, et al. Scrub typhus in children at a tertiary hospital in North India: Clinical profile and complications. Iran J Pediatr 2014;24:387-92.
Palanivel S, Nedunchelian K, Poovazhagi V, Raghunadan R, Ramachandran P. Clinical profile of scrub typhus in children. Indian J Pediatr 2012;79:1459-62.
Subbalaxmi MV, Madisetty MK, Prasad AK, Teja VD, Swaroopa K, Chandra N, et al. Outbreak of scrub typhus in Andhra Pradesh – experience at a tertiary care hospital. J Assoc Physicians India 2014;62:490-6.
Narvencar KP, Rodrigues S, Nevrekar RP, Dias L, Dias A, Vaz M, et al. Scrub typhus in patients reporting with acute febrile illness at a tertiary health care institution in Goa. Indian J Med Res 2012;136:1020-4.
Vivekanandan M, Mani A, Priya YS, Singh AP, Jayakumar S, Purty S. Outbreak of scrub typhus in Pondicherry. J Assoc Physicians India 2010;58:24-8.
Mathai E, Lloyd G, Cherian T, Abraham OC, Cherian AM. Serological evidence for the continued presence of human rickettsioses in Southern India. Ann Trop Med Parasitol 2001;95:395-8
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.
Sinha P, Gupta S, Dawra R, Rijhawan P. Recent outbreak of scrub typhus in North Western part of India. Indian J Med Microbiol 2014;32:247-50.
Huang CT, Chi H, Lee HC, Chiu NC, Huang FY. Scrub typhus in children in a teaching hospital in Eastern Taiwan, 2000-2005. Southeast Asian J Trop Med Public Health 2009;40:789-94.
Koh GC, Maude RJ, Paris DH, Newton PN, Blacksell SD. Diagnosis of scrub typhus. Am J Trop Med Hyg 2010;82:368-70.
Parola P, Paddock CD, Raoult D. Tick-borne rickettsioses around the world: Emerging diseases challenging old concepts. Clin Microbiol Rev 2005;18:719-56.
Dasari V, Kaur P, Murhekar MV. Rickettsial disease outbreaks in India: A review. Ann Trop Med Public Health 2014;7:249-54.
Prakash JA, Abraham OC, Mathai E. Evaluation of tests for serological diagnosis of scrub typhus. Trop Doct 2006;36:212-3.
Phimda K, Hoontrakul S, Suttinont C, Chareonwat S, Losuwanaluk K, Chueasuwanchai S, et al. Doxycycline versus azithromycin for treatment of leptospirosis and scrub typhus. Antimicrob Agents Chemother 2007;51:3259-63.
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[Table 1], [Table 2], [Table 3]