Scrub typhus is a life-threatening zoonotic disease caused by the bacteria Orientia tsutsugamushi. It is an obligate, intracellular, Gram-negative bacteria of Rickettsiae family isolated in 1930 [1]. The disease derives its name from the scrub vegetation where its vector, Leptotrombidium mite, resides. It is endemic to a geographically distinct region named the tsutsugamushi triangle, extending from Northern Japan and Eastern Russia in the North, to Australia in the South and Pakistan and Afghanistan in the West. Several cases have been reported from India, initially from Southern India and later on from the Himalayan belt spreading from Jammu and Kashmir in the North to Arunachal Pradesh in the East [2, 3].  The clinical symptoms of arthropod-borne diseases are overlapping in nature [4]. It is imperative for the clinicians in our country to keep in mind all options possible while treating a case of fever of unknown origin. Malaria being endemic is seldom seen in the Himalayan belt due to the high altitude. During the seasonal increase in dengue cases, simultaneous scrub typhus infection in endemic areas can be a diagnostic challenge. Both present with rash, thrombocytopenia, and hepatic dysfunction. Of late, there has been an increase in the number of coinfections with scrub typhus. These coinfections present with overt fulminating multiorgan dysfunction leading to rapid deterioration. Here we present a case report of a 40-year-old female with acute febrile illness from the Eastern part of Uttar Pradesh. 

A 40-year-old married female from Gorakhpur District presented to the Medicine OPD (outpatient department) of our hospital with fever for six days and vomiting for the last two days. The fever was high grade, continuous in nature, and associated with chills and rigors. She also gave a history of severe headache, nausea, and generalized body ache. On admission, she was conscious and oriented to time, place, and person.  Her blood pressure was 110/70 mm of Hg, pulse rate was 101 beats per minute, the temperature was 100°F, and respiratory rate was 24 per minute. On general physical investigation, there was diffuse maculopapular rash all over the body and hepatosplenomegaly with a liver span of 17cm and spleen was palpable 3cm below the left costal margins. Rest all systemic examinations did not reveal any abnormalities. On day 3 of admission, she became disoriented and was not able to maintain PO₂ following which she was intubated. A central line was also placed in the internal jugular vein for hemodynamic monitoring.  A blood sample was collected under aseptic precautions and sent for routine tests. Laboratory investigations showed thrombocytopenia (25,000/µL) with leukocytosis (30,000/mm³). Her coagulation parameters were deranged along with raised liver enzymes (ALT: 2000U/L, AST: 4000U/L) and creatinine (4mg/dl). Peripheral smear examination revealed no malarial parasite. With these findings on day 3, she was started empirically on Inj. Ceftriaxone 2gm IV/day. In spite of this, there were no signs of improvement and she continued to be in a comatose condition. As a result keeping in mind, all other common causes of febrile illness specific to this region (Leptospirosis, Dengue, Scrub typhus, Enteric fever, Japanese encephalitis) further tests were sent. The blood culture came out to be sterile. Surprisingly IgM/IgG antibody turned out positive for both dengue (SD Bioline Dengue Duo Test Kit, India) and scrub typhus (Bioline Tsutsugamushi Kit, Standard Diagnostics, Republic of Korea). A positive dengue test was on expected lines keeping thrombocytopenia in mind but scrub typhus was further confirmed by ELISA (Scrub Typhus Detect™ IgG and IgM ELISA System, In Bios International, USA). Rest all tests came out to be negative. Finally on day 6, a diagnosis of Scrub typhus with Dengue co-infection was made. Tab. Doxycycline 200 mg/day was added with the rest of the treatment being the same. On day 8 of admission, she regained consciousness and started improving clinically and defervescence was noted. Her laboratory parameters became stable and she was discharged and asked to follow up after 2 weeks.

In tropical areas, Scrub typhus and Dengue infection are the two most sought-after differential diagnoses in patients who present with acute febrile illness of uncertain etiology [5]. Dengue is a common arbovirus infection, transmitted by the bite of the vector Aedes aegypti mosquito [6]. Secondarily, Scrub typhus is also an important cause of febrile illness caused by a Gram-negative bacilli Orientia tsutsugamushi and is spread by infected chiggers biting in the scrub vegetation [7]. Many coinfections including malaria, chikungunya, leptospira, and viral hepatitis have been reported with dengue [8]. Particularly, during the seasonal increase in dengue cases, concomitant scrub typhus infection in endemic areas can present a diagnostic predicament. Both diseases have very analogous clinical and laboratory picture including rash, thrombocytopenia, and hepatic dysfunction. However, coinfection with both the pathogens is remarkably rare, primarily due to the different vectors and different mode of transmission involved [9]. In a study from Maharashtra, 15938 patients were admitted with acute febrile illness, dual infection of Dengue and Scrub typhus with prevalence rate was 0.15% was observed. Similar findings were noted by Raina et al in sub-Himalayan region i.e. prevalence of dual infection was 1.3% and Mittal et al in a state from southern India, where it was observed to be 1.88% [9-11]. Marked thrombocytopenia, significantly deranged liver function tests, and low albumin have been described in coinfections. Coinfections if not thought of in early stage can lead to prolonged hospital stay and may negatively affect the outcome [10-13]. During a seasonal overhauling of such febrile illnesses of infectious origin, the shortage of health care workers and resources often overwhelms the healthcare facility. This result in a suboptimal clinical management which leads to missing the presence of a coinfection. Physicians tend to follow the principle of Occam’s razor; which often leads to disregarding the presence of a difficult to diagnose coinfection. These coinfections, if left undiagnosed jeopardizes patient health status. Also, suspicion of scrub typhus permits early antibiotic treatment, which reduces the mortality of infection with O. tsutsugamushi. Similar to a study by Saleem et al, we also noted that our patient had leukocytosis rather than the anticipated leucopenia in Dengue, which can be a finding in co-infections [10]. Another challenging task for diagnostician and clinician is to rule out that these might be true mixed infections and not due to serological cross reactivity. Since IgM antibodies may occasionally persist longer than three months a false positive Dengue serology is difficult to rule out in such cases. Similarly a false positive serology for Scrub typhus can result owing to cross-reactivity. However since there was no history of similar complaints for at least 3 months prior to the episode it could be labelled as a co-infection [13]. Considering the diagnostic difficulties and the need for prompt and appropriate treatment, empirical use of doxycycline along with ceftriaxone should be empirically started in patients presenting with fever and multisystem involvement. With the use of doxycycline, remarkable clinical improvement happened which can hint towards diagnosis of scrub typhus as such a response cannot be expected in other usual infections [14-16].

Considering the diagnostic difficulties and the need for prompt and appropriate treatment, empirical use of doxycycline along with ceftriaxone should be empirically started in patients presenting with fever and multisystem involvement. With the use of doxycycline, remarkable clinical improvement happened which can hint towards diagnosis of scrub typhus as such a response cannot be expected in other usual infections.

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