| Abstract|| |
Scrub typhus is one of the tropical infections commonly seen in developing countries. The patients coming to health care centers with fever and thrombocytopenia should always be suspected for scrub typhus, along with malaria, dengue, and leptospiral infection. False-negative test or delay in the diagnosis can increase morbidity and mortality. We are reporting a series of five cases where the patients presented with fever to a local health care facility; on investigation, the patients were found to have thrombocytopenia. The dengue kit/card (qualitative test) test was found to be positive and the patients were treated accordingly; later, after 5 days, these patients noticed breathlessness and decreased urine output for which they were referred to a higher center and on further investigation, they were found to be negative for dengue serology (quantitative test) and positive for Weil-Felix test (WFT). All the five patients were successfully managed with invasive ventilator support and renal replacement therapy. This case report mainly emphasizes the suspicion of scrub typhus in patients with fever and thrombocytopenia, even if they are positive for other tropical infections, and timely doxycycline treatment, along with systemic supportive measure, are necessary for a successful outcome.
Keywords: False-negative test, scrub typhus, thrombocytopenia, Weil-Felix test (WFT)
|How to cite this article:|
Venkategowda PM, Prakash YS, Harde Y, Rao SM. Scrub typhus in false-positive dengue patients. Ann Trop Med Public Health 2015;8:34-6
|How to cite this URL:|
Venkategowda PM, Prakash YS, Harde Y, Rao SM. Scrub typhus in false-positive dengue patients. Ann Trop Med Public Health [serial online] 2015 [cited 2020 Jun 4];8:34-6. Available from: http://www.atmph.org/text.asp?2015/8/2/34/157279
| Introduction|| |
Scrub typhus, also known as "fever with stupor," is a mite-borne infectious disease caused by Orientia tsutsugamushi. It is one of the differential diagnoses for fever with thrombocytopenia.  It can manifest either with febrile illness and constitutional symptoms (e.g., fever, rash, myalgia, and headache) or with multiorgan dysfunction syndrome. 
In untreated patients, the mortality range is 0-30%. Studies have shown that delay in diagnosis/initiation of treatment with doxycycline can lead to multiorgan dysfunction syndrome, which has high morbidity and mortality. Physicians should have high suspicion for scrub typhus in those patients presenting with fever and thrombocytopenia. The patients who are positive for one tropical infection can have coinfection with other tropical infections since they also have similar clinical presentations. Dengue kit test, in our case series, had falsely diagnosed the scrub typhus patients as being dengue infected, which resulted in delay in the diagnosis and treatment with doxycycline.
| Case Report|| |
This is a case series of five patients who were referred to our hospital (a multispecialty hospital) from other primary health care centers. All the five patients were diagnosed as having dengue fever (fever with thrombocytopenia and the dengue card/kit test was positive) and were initially managed with supportive measures and later, after 4 days, all of them developed breathlessness and decreased urine output; hence, they were referred to our hospital.
The clinical features of these patients are shown in [Table 1]. The most common clinical features are fever and headache. The other features are nausea, vomiting, myalgia, generalized weakness, pain in the abdomen, conjunctival congestion, decreased urine output, altered sensorium, hepatosplenomegaly, and maculapapular rashes. The laboratory features, on admission, are shown in [Table 2]. These patients had decreased hemoglobin and platelets, increased serum creatinine, serum total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK). The complications that were seen in these five patients are shown in [Table 3]. The common complications were acute kidney injury (AKI), elevated liver enzymes, and hypotension due to hypovolemia. All the five patients had AKI and underwent renal replacement therapy [sustained low efficiency dialysis (SLED)] for 2 weeks. The other complications were acute respiratory distress syndrome (ARDS), myopathy, encephalitis, myocarditis, and upper gastrointestinal (GI) bleed. Four patients were intubated and mechanically ventilated. All the five patients were successfully managed and discharged. The length of intensive care unit (ICU) stay was 6.8 days (average).
| Discussion|| |
Scrub typhus is a tropical infection caused by an obligate intracellular gram-negative bacterium Orientia tsutsugamushi, transmitted to humans who are accidental hosts through mites that are believed to be both the vectors and the reservoirs.  A billion people are at risk and nearly a million cases are reported every year. Scrub typhus is endemic in the so-called "tsutsugamushi triangle" like Japan, Taiwan, China, and South Korea in the north, India and Nepal in the west, and Australia and Indonesia in the south. Scrub typhus can manifest either with febrile illness and constitutional symptoms (e.g., fever, rash, myalgia, and headache) or with multiorgan dysfunction syndrome.
Scrub typhus can involve almost all the organs (e.g., kidney, lungs, heart, liver, and the central nervous system). Involvement of the lungs has been described, which ranges from the bronchitis and the interstitial pneumonitis to the ARDS.  Eschar, which is pathognomonic of scrub typhus, is often found in the groin, the axilla, the genitalia, and the neck.
Diagnosis is based on serology or immunoflorescence antibody test; indirect immunoperoxidase assay is the gold standard.  The serological test will be positive only in the second week and scrub typhus occurs rarely due to nonspecific clinical features.
Immunochromatography test (ICT) and Weil-Felix test (WFT) are commonly performed tests to diagnose scrub typhus due to the nonavailability and cost factors, since these tests also have high specificity. ,
Doxycycline is the drug of choice for the treatment of scrub typhus and the usual therapy is for 10-14 days. Rifampicin can be used in combination with azithromycin or doxycycline in cases of poor response to doxycycline alone. All our patients responded to doxycycline therapy alone and were later discharged.
Fever with thrombocytopenia can be a manifestation of multiple tropical infections. The incidence of coinfections in recent years has been high and a patient diagnosed with dengue infection can also have other coinfections, which are commonly missed if we do only one diagnostic test.. Hence, morbidity and mortality can be increased if diagnosis is not done or if there is a delay in the diagnosis. In our study, all the five patients who were initially tested for dengue using the dengue kit test, actually had scrub typhus and were falsely diagnosed as having dengue fever and treated accordingly. The kit test, which is commonly used in resource-limited countries, has high false-positive results. Quantitative serological test is always better, which has high sensitivity and specificity. Patients having fever with thrombocytopenia and multiple organ dysfunction syndrome (MODS) should always be suspected for having more than one tropical infection and be evaluated accordingly in order to reduce morbidity and mortality.
| Acknowledgments|| |
We gratefully acknowledge the physicians, nephrologist, cardiologist, gastroenterologist, respiratory therapists, nurses, and the management of the hospital for their valuable support.
| References|| |
Tamura A, Ohashi N, Urakami H, Miyamura S. Classification of Rickettsia tsutsugamushi in a new genus, Orientia gen. nov., as Orientia tsutsugamushi comb. nov. Int J Syst Bacteriol 1995;45:589-91.
Kothari VM, Karnad DR, Bichile LS. Tropical infections in the ICU. J Assoc Physicians India 2006;54:291-8.
Mahajan SK. Scrub typhus. J Assoc Physicians India 2005;53:954-8.
Lerdthusnee K, Khuntirat B, Leepitakrat W, Tanskul P, Monkanna T, Khlaimanee N, et al
. Scrub typhus: Vector competence of Leptotrombidium chiangraiensis chiggers and transmission efficacy and isolation of Orientia tsutsugamushi. Ann N Y Acad Sci 2003;990:25-35.
Chayakul P, Panich V, Silpapojakul K. Scrub typhus pneumonitis: An entity which is frequently missed. Q J Med 1988;68:595-602.
Koh GC, Maude RJ, Paris DH, Newton PN, Blacksell SD. Diagnosis of scrub typhus. Am J Trop Med Hyg 2010;82:368-70.
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.
Kamarasu K, Malathi M, Rajagopal V, Subramani K, Jagadeeshramasamy D, Mathai E. Serological evidence for wide distribution of spotted fevers and typhus fever in Tamil Nadu. Indian J Med Res 2007;126:128-30.
Pradeep M Venkategowda
Shantishikara Apartments, D4, #124, Bedind Enadu Bld, Rajbhavan Road, Somajiguda, Hyderabad - 500 082, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3]