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ORIGINAL ARTICLE
Year : 2020  |  Volume : 18  |  Issue : 2  |  Page : 111-114

Scrub typhus: Clinical presentation and severity


Department of Emergency Medicine, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission27-Jan-2020
Date of Decision02-Feb-2020
Date of Acceptance09-Mar-2020
Date of Web Publication17-Apr-2020

Correspondence Address:
Dr. Darpanarayan Hazra
Department of Emergency Medicine, Christian Medical College, Vellore - 632 004, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmi.cmi_10_20

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  Abstract 

Background: Scrub typhus is an acute zoonotic febrile illness caused by the obligate intracellular bacteria Orientia tsutsugamushi. In the Indian subcontinent, there has been mounting evidence in the past few years, indicating that it is one of the most prevalent, yet underrecognized entity, probably as a result of its varied presentation, lack of awareness, and hence, a low index of suspicion among clinicians. Materials and Methods: This is a subgroup analysis involving patients diagnosed to have scrub typhus from a large prospective study on patients presenting with acute undifferentiated febrile illness (AUFI) done between October 2012 and September 2013. Results: A total of 452 patients met the eligibility criteria and were included in the final analysis. The mean age of the cohort was 42.7 (standard deviation [SD] 15.1) years and female predominance (266, [58.8%]) was noted. The mean duration of fever was 8.2 (SD 3.2) days. The most common clinical features were chills, generalized myalgia, and breathlessness. A characteristic eschar was noted in 262 (57.9%) patients. Overall, the most common comorbidities were diabetes mellitus, followed by hypertension. Majority of patients were started on doxycycline or azithromycin empirically on clinical suspicion. Among the total study population, 21 (4.6%) patients succumbed to the disease condition and the rest were discharged stable either from the outpatient department or ward. Conclusion: Scrub typhus is one of the most common causes of AUFI in our locality and comprises a third of these cases. The pathognomonic eschar which is present in almost two-third of patients offers a vital clue for the diagnosis of scrub typhus.

Keywords: Acute undifferentiated febrile illness, eschar, Orientia tsutsugamushi, rickettsia, scrub typhus


How to cite this article:
Hazra D, Fernandes JP, Nekkanti AC, Abhilash KP. Scrub typhus: Clinical presentation and severity. Curr Med Issues 2020;18:111-4

How to cite this URL:
Hazra D, Fernandes JP, Nekkanti AC, Abhilash KP. Scrub typhus: Clinical presentation and severity. Curr Med Issues [serial online] 2020 [cited 2020 May 30];18:111-4. Available from: http://www.cmijournal.org/text.asp?2020/18/2/111/282774




  Introduction Top


Scrub typhus is an acute zoonotic febrile illness caused by the obligate intracellular bacteria Orientia tsutsugamushi which is a small Gram-negative obligate intracellular coccobacillus and spread by the bite of larva of trombiculid mites (chiggers), which also act as the reservoirs for the bacteria.[1],[2],[3],[4] Humans are infected by the bite of the larval stage of trombiculid mites which spreads by the blood and lymphatics to various parts of the body and induces generalized vasculitis by direct infection of the endothelium of the small blood vessels.[3],[4],[5] In the Indian subcontinent, there has been mounting evidence in the past few years, indicating that it is one of the most prevalent, yet underrecognized entity, probably as a result of its varied presentation, lack of awareness, and hence, a low index of suspicion among clinicians. It is also endemic throughout the Asia-Pacific region where an estimated one million new cases occur each year. The disease may be far more widespread since isolated reports have also emerged from Africa and South America, besides reports of infection in travelers returning to Germany, France, and the USA.[6],[7]

Clinical features of scrub typhus vary from mild fever with malaise to multi-organ failure and death. Most common presentation is that of an acute undifferentiated febrile illness (AUFI) with headache, myalgia, transient maculopapular rash, dyspnea, vomiting, pneumonitis, and altered sensorium. A characteristic eschar representing localized skin necrosis at the site of the bite by the chigger is only present in a minority of patients.[4],[5],[6] Severe forms of scrub typhus present with involvement of virtually any organ system, most commonly pneumonia, acute respiratory distress syndrome, acute kidney injury, meningoencephalitis, disseminated intravascular coagulation, shock, and hemorrhage.[1],[3],[4],[5] We conducted this study to observe and assess the clinical presentation, disease severity, and outcome of patients presenting with scrub typhus to our institution.


  Materials and Methods Top


Study design

This is a subgroup analysis involving patients diagnosed to have scrub typhus from a large prospective study on patients presenting with AUFI done from October 2012 to September 2013.[1]

Setting

We conducted this study in the Adult Emergency Department and General Medicine Department of Christian Medical College and Hospital, Vellore, a 2700-bed tertiary care hospital in Tamil Nadu, South India, between October 2012 and September 2013.

Participants

All patients with an eschar and scrub IgM ELISA positive or scrub IgM ELISA positive with other serologies and blood culture negative or scrub IgM ELISA seroconversion on convalescent sera were included in the study.

Exclusion criteria

Charts with incomplete data and patients with other etiologies for an AUFI were excluded from the study.

Variables

Patient data were obtained through the hospital's electronic database. Details of history and physical examination findings and demographic details were recorded on a standard data collection sheet. The variables included were age, sex, comorbidities, clinical features, examination findings, and laboratory results.

Outcome variable

Outcome variables include hospital outcome of patients with scrub typhus infection.

Study size

As one of the objectives is to determine the seasonal variation, we recruited patients over a period of 1-year duration.

Laboratory test

Blood investigations included serum electrolytes, liver and renal function tests, and complete blood count analysis. Single blood culture was obtained from all the enrolled patients in an aerobic BacT/ALERT 3D (bioMérieux, Hazelwood, MO, USA) bottle and was incubated for up to 7 days. Scrub typhus IgM ELISA (InBios International, Inc., Seattle, WA, USA) was interpreted according to the manufacturer's instruction as positive, equivocal, or negative.

Statistical analysis

Details of history and results of a thorough physical examination were entered on a standard data collection sheet after obtaining written informed consent. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS Inc., Released 2007, SPSS for Windows, and version 16.0, Chicago, IL, USA). Mean with standard deviation (SD) was calculated for the continuous variables. Categorical variables were expressed as a proportion.

Ethical considerations

The study was approved by the Institutional Review Board (IRB Min. No. 8007 dated 19/09/2012), and the patient's confidentiality was maintained using unique identifiers and password-protected data entry software with restricted users.


  Results Top


During the study period, 1372 patients were screened for an AUFI. After applying the exclusion criteria, 1258 patients were evaluated for etiology of the AUFI. In our study, we included the 452 patients who were confirmed to have scrub typhus [Figure 1].
Figure 1: STROBE diagram

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The mean age of the cohort of scrub typhus patients was 42.7 (SD 15.1) years and female predominance (266, [58.8%]) was noted. Overall, the most common comorbidities were diabetes mellitus (n = 96; 21.2%) and hypertension (n = 73; 16.1%). The distribution of each comorbid condition along with the baseline characteristics is shown in [Table 1].
Table 1: Baseline characteristics and comorbidities

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All patients included in the study had either fever with an eschar with scrub IgM ELISA positive, or scrub IgM ELISA positive with other serologies and blood culture negative, or scrub IgM ELISA seroconversion on convalescent sera. The mean duration of fever was 8.2 (SD: 3.2) days. The most common clinical features overall were chills (n = 391; 86.5%), generalized myalgia (n = 332; 73.5%), and breathlessness (n = 217; 48%), followed by headache (n = 260; 57.5%), nausea and vomiting (n = 209; 46.2%), seizures (n = 17; 3.8%), altered sensorium (n = 55; 12.2%), and neck stiffness (n = 34; 7.5%) [Table 2]. A characteristic eschar was noted in 262 (57.9%) patients. The physical examination findings and common sites of bleeding are shown in [Table 2].
Table 2: Clinical features and physical examination findings

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The laboratory findings are shown in [Table 3]. The overall mean hemoglobin was 13 (SD: 2.9) g/dL. A significant number of patients (79.6%) had thrombocytopenia at the initial presentation.
Table 3: Laboratory investigations

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The severity at the presentation in the first 24 h was assessed by sequential organ failure assessment (SOFA) score, as shown in [Table 4].
Table 4: Disease severity scoring

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Supplemental oxygen was needed in 39.1% of the patients of scrub typhus, while 10 patients required one or more sessions of hemodialysis. Invasive ventilation was required in 13.9% of the patients with scrub typhus infection [Table 5].
Table 5: Requirements of supports

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Most patients were initiated on doxycycline or azithromycin empirically on clinical suspicion, even before the IgM ELISA results for scrub typhus were available and had an uneventful hospital stay. Among the total study population, 21 (4.6%) patients succumbed to the infection.


  Discussion Top


India is a tropical country with a high burden of febrile zoonotic/infectious illnesses, scrub typhus being such a cause with multiple epidemics reported from various regions of India, especially the hilly regions of the Himalayas, Assam, West Bengal, and Tamil Nadu. The incubation period of scrub typhus in humans is around 10–12 days and can vary between 6 and 21 days.[3],[4],[5] Scrub typhus usually presents with fever associated with nonspecific features involving multiple organ systems. In a tropical country such as India, varied clinical presentations in association with lacunae in diagnostic facilities have become the major contributors to the reoccurrence of this disease.[5],[6],[7] A characteristic eschar representing localized skin necrosis at the site of the bite by the chigger was present in 262 (57.9%) patients. Literature review suggests that the prevalence of an eschar is highly variable, from 7% to 80%, and this variation may be due to differences in the eschar-inducing capacity of different strains of the organism, difficulties in identifying the eschar in dark-skinned individuals, and the atypical appearance of eschars in skinfolds and moist skin.[4] Previous study from our center reported that the groin, axilla, waist, neck, and other exposed parts of the body are the most common sites.[4] Many of the cases of scrub typhus were reported during the monsoon and postmonsoon seasons, in accordance with the reported patterns of disease transmission. These patients presented to us with 8.2 (SD 3.2) days of fever associated with chills and myalgia in majority of them. The SOFA score was calculated at the baseline for all patients. The elevated score likely reflects the multi-organ involvement that is typical of scrub typhus. A SOFA score of 2 or more at admission is a predictor of mortality for patients with sepsis if the baseline SOFA score prior to illness is 0 for all patients.[7] In the present study, a SOFA score ranging from 2 to 4 was present in a high proportion of patients with scrub typhus when compared to other patients with AUFI.

Most patients were started on doxycycline or azithromycin empirically on clinical suspicion, even before the IgM ELISA results for scrub typhus were available. The case fatality rate among inpatients of scrub typhus in our hospital decreased from 12.2% in 2008 to 6.9% in our study. This is probably due to appropriate algorithms for the diagnosis and management of scrub typhus infection that have been devised at our center based on our previous studies.[1],[8] This retrospective analysis is an attempt to contribute our experiences related to scrub typhus to enhance the database for future references.


  Conclusion Top


Scrub typhus should always be considered as an important differential diagnosis in patients presenting with AUFI associated with organ involvement, in areas where scrub typhus is prevalent. Awareness of these unusual manifestations will hopefully guide clinicians toward diagnosing the condition early and initiating early appropriate antibiotics and other supportive measures.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Research quality and ethics statement

The authors of this manuscript declare that this scientific work complies with reporting quality, formatting, and reproducibility guidelines set forth by the EQUATOR Network. The authors also attest that this clinical investigation was determined to require Institutional Review Board/Ethics Committee review, and the corresponding protocol/approval number is IRB Min No: 10622 dated June 12, 2017. We also certify that we have not plagiarized the contents in this submission and have done a Plagiarism Check.



 
  References Top

1.
Abhilash KP, Jeevan JA, Mitra S, Paul N, Murugan TP, Rangaraj A, et al. Acute undifferentiated febrile illness in patients presenting to a tertiary care hospital in South India: Clinical spectrum and outcome. J Glob Infect Dis 2016;8:147-54.  Back to cited text no. 1
    
2.
Fernandes JP, Hazra D, David SN, Abhilash KP. Acute undifferentiated febrile illness in the elderly: A clinical profile. Curr Med Issues 2019;17:103-7.  Back to cited text no. 2
  [Full text]  
3.
Chrispal A, Boorugu H, Gopinath KG, Chandy S, Prakash JA, Thomas EM, et al. Acute undifferentiated febrile illness in adult hospitalized patients: The disease spectrum and diagnostic predictors-An experience from a tertiary care hospital in South India. Trop Doct 2010;40:230-4.  Back to cited text no. 3
    
4.
Kundavaram AP, Jonathan AJ, Nathaniel SD, Varghese GM. Eschar in scrub typhus: A valuable clue to the diagnosis. J Postgrad Med 2013;59:177-8.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Suttinont C, Losuwanaluk K, Niwatayakul K, Hoontrakul S, Intaranongpai W, Silpasakorn S, et al. Causes of acute, undifferentiated, febrile illness in rural Thailand: Results of a prospective observational study. Ann Trop Med Parasitol 2006;100:363-70.  Back to cited text no. 5
    
6.
Mahajan SK, Rolain JM, Kashyap R, Bakshi D, Sharma V, Prasher BS, et al. Scrub typhus in Himalayas. Emerg Infect Dis 2006;12:1590-2.  Back to cited text no. 6
    
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Prasanth B, Navneet S, Sushil K, Ashish B, Manisha B, Use of critical illness scoring systems (SOFA, APACHE II and qSOFA) to predict the clinical outcomes in scrub typhus patients with organ dysfunctions. Open Forum Infect Dis 2016;3 Suppl_1:618.  Back to cited text no. 7
    
8.
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.  Back to cited text no. 8
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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