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Year : 2020  |  Volume : 17  |  Issue : 2  |  Page : 101-104

Clinical manifestations and complications seen with scrub typhus: A case series from indore

1 Consultant Rheumatologist, Apollo Hospitals, Indore, Madhya Pradesh, India
2 Resident, M.G.M Medical College and M.Y. Hospital, Indore, Madhya Pradesh, India
3 Consultant Gastroenterologist, Apollo Hospitals, Indore, Madhya Pradesh, India
4 Department of Medicine, M.G.M Medical College and M.Y. Hospital, Indore, Madhya Pradesh, India

Date of Submission22-Apr-2020
Date of Acceptance05-May-2020
Date of Web Publication18-Jun-2020

Correspondence Address:
Akshat Pandey
A-4 MIG Colony, Behind Hotel Amaltas, Indore, Madhya Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/am.am_26_20

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Scrub typhus is a zoonotic disease caused by the bite of a mite Orientia tsutsugamushi, a bacterium from the Rickettsiaceae family, which is transmitted to humans by bite of trombiculid mite. Scrub typhus is widely spread all across India, and despite its vast occurrence, it remains underdiagnosed. The probable reasons could be the lack of specific symptoms, poor access to the diagnostic facilities, and low index of suspicion by the clinicians. It is a common trend to rule out the common causes of infection such as malaria, typhoid, and leptospirosis, and then, a good number of cases are ultimately diagnosed as scrub typhus. The common presentation is high-grade fever (98%), tender regional/generalized lymphadenopathy (40%–97%), hepatosplenomegaly, cough, and a characteristic eschar that is found in nearly 50% of cases, which represents the site of bite by the mite. Here, we present with a series of cases from Indore of scrub typhus with pulmonary complications which too were underdiagnosed. Immunoglobulin M typhus (enzyme-linked immunosorbent assay) confirmed the diagnosis, and all three were efficiently managed with doxycycline.

Keywords: Eschar, pleural effusion, zoonotic disease

How to cite this article:
Pandey A, Nigam A, Chaudhary A, Pandey V P. Clinical manifestations and complications seen with scrub typhus: A case series from indore. Apollo Med 2020;17:101-4

How to cite this URL:
Pandey A, Nigam A, Chaudhary A, Pandey V P. Clinical manifestations and complications seen with scrub typhus: A case series from indore. Apollo Med [serial online] 2020 [cited 2020 Jul 11];17:101-4. Available from: http://www.apollomedicine.org/text.asp?2020/17/2/101/287085

  Introduction Top

Scrub typhus wasfirst diagnosed in Japan in 1899, and it was a dreaded disease in the preantibiotic era and a major concern during World War II where it occurred as an epidemic. In India, thefirst outbreak occurred in West Bengal and Assam during World War II.[1] An estimated 1 billion people are at risk for scrub typhus, and every year, around 1 million cases occur, and in the Indian subcontinent, scrub typhus is the most commonly reported rickettsial infection.[2],[3] Scrub typhus is prevalent throughout India, particularly Southern India, Northern India, Northeastern states, and Central India.[4] It is transmitted to humans and rodents by bite of infected trombiculid mite.[5] The bite leaves an initial vesicular lesion which later on becomes a characteristic eschar or an ulcer with regional lymphadenopathy. The eschar is the single most important clue for diagnosis and is pathognomonic when examined by an experienced physician. The frequency of eschar is highly variable from 7% to 97% in endemic areas and is frequently found in covered areas such as groin, axilla, chest, or lower back.[6] After the bite of infected mite, it usually follows an incubation period of 6–21 days (mean, 10–12 days).

The common presenting features of the disease are fever which rises in the 1st week with severe headache, lymphadenopathy, hepatosplenomegaly, abdominal pain, drowsiness, a macular rash, maculopapular rash, and intensely colored development on the trunk during the 5th–8th day of fever often extending to the arms and legs. The disease may get complicated if left untreated and may land up in life-threatening complications such as interstitial pneumonitis, acute respiratory distress syndrome (ARDS), acute hepatic failure, acute renal failure, disseminated intravascular coagulation, meningitis, and myocarditis.[7] Physical examinations may mimic other diseases such as malaria, enteric fever, dengue, conjunctival chemosis and edema, generalized or local lymphadenopathy, hepatomegaly, splenomegaly, and ascites which are found in many cases making it a common differential diagnosis in febrile illness. Febrile encephalopathy is an infrequent presentation in adults but more common in children.

The public health importance of this disease is underestimated because of the difficulties of clinical diagnosis and lack of laboratory methods in many geographic areas. Here, we are presenting case series of various manifestations of scrub typhus from Indore.

  Case Reports Top

Case I

A 50-year-old farmer from a rural area presented with complaints of abdominal pain, yellowish discoloration of the sclera, and anorexia for 15 days. The patient had received medications from outside but showed no signs of improvement. There was no significant history of (H/O) alcohol addiction or jaundice in the past.

His physical examination showed a pulse rate of 98/min, blood pressure of 130/78 mmHg, oxygen saturation of 98%, and body temperature of 100.2°F with normal respiratory rate. General examination revealed icterus but no pallor or lymphadenopathy. Abdominal examination showed a palpable liver, which was nontender, and splenomegaly.

His laboratory investigations had the most striking features with raised erythrocyte sedimentation rate of 52 mm/h, deranged liver function tests (LFTs) with an elevated total bilirubin of 9.48 mg/dL, direct bilirubin of 9.04 mg/dL, Aspartate transaminase/alanine transaminase of 106 U/L/152 U/L, Albumin:Globulin (A:G) ratio reversal suggesting acute hepatocellular injury. The patient was initially evaluated for malaria, but both thick and thin peripheral smears were negative, markers of hepatitis were negative, twice blood cultures were sterile, and Leptospira immunoglobulin M (IgM) was negative.

On a repeat detailed examination, the patient had an eschar over the left forearm [Figure 1] and he was subsequently evaluated for IgM typhus enzyme-linked immunosorbent assay (ELISA), and the result was positive. Thus, the patient was diagnosed with scrub typhus and was initiated on doxycycline 100 mg twice a day. The patient started to respond, and within 2 days, his body temperature returned to normal and his LFTs showed striking improvement to total bilirubin of 3.09 mg/dL, direct bilirubin of 2.08 mg/dL, and complete normalization of LFTs after day 10.
Figure 1: Eschar over the left forearm

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Case II

A 60-year-old female resident of a rural area who was a homemaker presented to the hospital with complaints of loose stools for 15 days, anorexia, fever, and shortness of breath for 10 days with drowsiness for 2 days. The patient showed no response to treatment received outside. There was no past H/O medical or surgical illness.

On physical examination, the patient was febrile (99.4°F), pulse rate was 110/min with low volume, blood pressure of 96/66 mmHg, and a respiratory rate of 38/min, with an oxygen saturation of 88% on room air. The patient appeared dehydrated and dyspneic on general examination. Her systemic examination revealed bilateral (B/L) crepitations with B/L wheeze.

In her laboratory investigations, she had pancytopenia (Hemoglobin – 5.3 g/dL, White blood cells– 2800/mm3, and Platelet count – 11,000/mm3), her Reticulocyte count was 0.3%, peripheral blood smear showed microcytic hypochromic anemia. Her SGOT was 900U/L and SGPT was 600 U/L with an increased serum creatinine of 2 mg/dL. Her chest X-ray (CXR) showed B/L pleural effusions with B/L reticular opacities. Arterial blood gas revealed hypoxia (PaO2 60 mmHg). The patient's urine analysis was unremarkable, and she was given intravenous fluids and antibiotics.

Markers for hepatitis A, hepatitis B, hepatitis C, and hepatitis E were negative; sputum routine examination showed few Gram-positive cocci with epithelial cells; sputum acid-fast stain and tuberculosis-polymerase chain reaction were negative; stool analysis was normal; blood cultures were sterile; and malaria parasite was not identified in a repeated thick and thin smear. The patient was found to have an eschar over the right thigh [Figure 2] and her IgM typhus (ELISA) came positive. She was started on tablet doxycycline 100 mg twice a day to which she showed gradual improvement in terms of her clinical status, CXR, and liver functions, and within 1 week, the patient recovered completely.
Figure 2: Eschar over the Left Inguinal region

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Case III

A 40-year-old female, hailing from a rural area, homemaker, presented to the hospital with complaints of high-grade fever with chills, nonproductive cough, and abdominal pain for the past 10–12 days. The patient was a known case of rheumatoid arthritis (RA) and secondary Sjogren's syndrome for the past 10 years with ongoing treatment.

On admission, the patient was febrile, temperature of 100°F, pulse rate of 120/min, with blood pressure of 100/60 mmHg and saturation of 99% with a respiratory frequency of 20/min suggesting that the patient was febrile and hemodynamically stable on admission. The patient appeared pale and toxic. General examination revealed pallor; respiratory system examination revealed B/L rhonchi and wheeze diffusely scattered all over the lung fields. Her laboratory investigations revealed striking features were severe anemia with hemoglobin of 6 g/dL (normocytic normochromic), abdominal ultrasound showed mild splenomegaly, and computed tomography of the chest showed B/L reticulonodular opacities and mild pleural effusions suggesting a multi system involvement. The patient was treated with broad-spectrum antibiotics and antivirals, but she did not respond; her repeat blood cultures were sterile, but on detailed reexamination, an eschar over the right thigh [Figure 3] was identified, and the patient was found to be positive IgM for scrub typhus; thereafter, she was started on doxycycline with gradual improvement in her symptoms and recovered.
Figure 3: Eschar over right thigh

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  Discussion Top

Scrub typhus is a zoonotic infection caused by Gram-negative bacteria Orientia tsutsugamushi which is transmitted by the larvae of trombiculid mites. It is one of the most neglected infections due to underdiagnosis despite an annual incidence of 1 million cases worldwide. In endemic areas, if not diagnosed or treated earliest, it can cause mortality in 30%–50% of cases.[8]

The clinical presentation of scrub typhus varies from acute flu-like symptoms to severe multiorgan dysfunction such as acute renal injury, ARDS, hepatitis, and myocarditis.[9],[10],[11] There can be regional or generalized lymphadenopathy and the presence of the characteristic eschar at the site of inoculation by the mite.[12] It is seen as a black necrotic center and erythematous borders, mostly in the axilla, neck extremities, or groin.

Fever of unknown origin could raise a probable suspicion for this infection. The usual scenario includes ruling out other causes for fever such as malaria, dengue, and leptospirosis.[13] Most of the cases of scrub typhus occur from rural areas or people living near fields or grasslands. Scrub typhus is suspected by a constellation of clinical features with the presence of characteristic eschar. In the above series, in all three cases, eschar was missed to be detected on the initial examination. It was only after ruling out other probable causes of infection; on reexamination, it was detected.

Pulmonary affection has been a common complication of scrub typhus infection with 58.4% incidence presenting as cough or dyspnea.[14] Almost 59%–72% of cases show radiological abnormalities as interstitial pneumonia, hilar adenopathy, pleural effusion, and consolidation. In the above series, the second and third cases had pulmonary involvement with pleural effusion and reticulonodular opacities, which was detected as crepitations, wheeze, and rhonchi on examination. All the three cases had hepatic involvement as hepatomegaly or acute hepatitis showing the severity of the infection. The third case had other comorbidities such as RA and secondary Sjogren's syndrome and was on medications for the same.

Once the suspicion of typhus is made, it can be evaluated by various methods available, one of the cheapest and most easily available tests being Weil–Felix test. Fifty percent of patients have a positive test during the 2nd week of illness, but it lacks sensitivity and specificity.[15] ELISA for the detection of IgM antibodies against O. tsutsugamushi is available. The gold standard test is indirect immunofluorescence assay but has limited use due to its cost. The organism can be grown in tissue culture or mice from the blood of patients with scrub typhus. Isolation of O. tsutsugamushi requires biosafety level 3 facilities, and the median time to positivity is 27 days.

In the above series, all the three cases were diagnosed for scrub typhus by the presence of IgM typhus (ELISA). Scrub typhus patients with tachycardia, low body temperature, crepitations on examination, low percentage of lymphocytes, hypoalbuminemia, elevated serum creatinine, elevated aspartate aminotransferase, and presence of urinary albumin should be monitored closely for severity progression.[16] One Indian study shows that the presence of eschar indicates a poor prognosis in scrub typhus.[17]

Early suspicion, diagnosis, and treatment with appropriate antibiotics can prevent morbidity and mortality in scrub typhus. Doxycycline or tetracyclines are the drug of choice or chloramphenicol can be an alternative. The recommended duration of therapy is 7–14 days, and in severe cases, intravenous doxycycline should be considered. Therapeutic response in the form of rapid defervesce (in 48 h) can be taken as an indirect marker of diagnosis.[18] In pregnant females and infants, azithromycin is the drug of choice. It has shown to have comparable efficacy when compared with doxycycline in a study [19] with a smaller sample size. Rifampicin has also shown to have efficacy as an alternate drug, but it should not be used alone because of the high risk of resistance. A combination therapy with doxycycline and rifampicin should be used in areas showing resistance to doxycycline alone.[19]

  Conclusion Top

Scrub typhus is a common cause of acute febrile illness in India and an important differential diagnosis of other infections due to varied representations. The main challenge in its management is an early high index of suspicion and diagnosing despite poor resource setting, especially in the absence of eschars. Due to its nonspecific clinical presentation and limited awareness with inadequate diagnostic tests, in majority of cases, it is misdiagnosed. Specific therapy like doxycycline administration on time can reduce morbidity and mortality.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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