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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 9  |  Issue : 4  |  Page : 268-271

Co-infection of scrub typhus and COVID-19: A diagnostic challenge


Department of General Medicine, Government Medical College and Hospital, Chandigarh, India

Date of Submission28-Jul-2021
Date of Decision07-Aug-2021
Date of Acceptance08-Aug-2021
Date of Web Publication20-Oct-2021

Correspondence Address:
Dr. Gautam Jesrani
Department of General Medicine, Level-4, D-Block, Government Medical College and Hospital, Sector 32, Chandigarh - 160 030
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajim.ajim_81_21

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  Abstract 


Scrub typhus is a bacterial disease, caused by Orientia tsutsugamushi and has widespread clinical presentations. Coronavirus-19 disease (COVID-19) is an ongoing pandemic, which can demonstrate clinical symptoms similar to the scrub typhus. Herein, we are describing two such cases of scrub typhus and COVID-19 co-infection. A 35-year-old male and a 42-year-old female presented with respiratory failure, for which COVID-19 was diagnosed, but both of them had persistent thrombocytopenia. The patients were investigated for other tropical co-infections and the diagnosis of scrub typhus was established in both of the cases. Doxycycline was added to their ongoing treatment, which led to an uneventful recovery. The cases highlight the importance of keeping a high index of suspicion of concurrent infection in the regions where seasonal tropical infections are endemic.

Keywords: Anti-coagulants, coronavirus-19 disease, doxycycline, scrub typhus, thrombocytopenia


How to cite this article:
Jesrani G, Chhabra A, Garg A, Kaur A, Gupta M. Co-infection of scrub typhus and COVID-19: A diagnostic challenge. APIK J Int Med 2021;9:268-71

How to cite this URL:
Jesrani G, Chhabra A, Garg A, Kaur A, Gupta M. Co-infection of scrub typhus and COVID-19: A diagnostic challenge. APIK J Int Med [serial online] 2021 [cited 2021 Nov 29];9:268-71. Available from: https://www.ajim.in/text.asp?2021/9/4/268/328684




  Introduction Top


The world is currently experiencing the pandemic of coronavirus-19 disease (COVID-19), which originated in the Wuhan city, China, and involved almost every geographic region of the world. This viral disease predominantly presents with the respiratory symptoms, but thrombocytopenia like hematological abnormalities are not uncommon.[1] On the other hand, scrub typhus is a mite borne, seasonal tropical disease, and well known for having thrombocytopenia in the course of illness. It spreads due to the bite of larvae mite and forms a typical skin necrosis “Eschar.”[2] The disease is predominantly seen in the Asian pacific zone and individuals residing in this region are thus predisposed to incidental co-infection with COVID-19 and scrub typhus.


  Case Reports Top


Case 1

A-35-year-old male presented to the emergency department with the history of breathlessness and fever from the past 5 days. On presentation, the patient had temperature 39.2° C, respiratory rate 32/min, and capillary oxygen saturation (SpO2) 83% under room air (RA). Oxygen (O2) supplementation with venturi mask (VM) at 10 L/min which improved his SpO2 to 93%. Chest radiograph demonstrated bilateral peripheral infiltrates [Figure 1] due to which, the patient underwent reverse transcription polymerase chain reaction (RT-PCR) for COVID-19 and tested positive. On further evaluation, his complete blood count (CBC) demonstrated leukocytosis of 19.8 × 109/L (normal 4–11) and thrombocytopenia of 16 × 109/L (Normal 150–450). He was started on dexamethasone 6 mg once a day. However, we did not commence anti-coagulation therapy due to thrombocytopenia. In addition, high-resolution computed tomography of the chest depicted diffuse ground glass opacities in bilateral lung fields with a computed tomography severity index of 14/25 [Figure 1]. By day 3 of illness, his O2 requirement reduced, but he continued to have fever with thrombocytopenia. Inflammatory work up demonstrated d-dimer levels of 0.9 μg/mL (normal <0.5), serum ferritin of 643 ng/mL (normal 22–322 for male), interleukin 6 (IL-6) of 7 pg/mL (normal 4–12), and C-reactive protein (CRP) levels of 14 mg/L (normal <5). A thorough re-evaluation demonstrated an eschar mark on his right nipple [Figure 2] which prompted us to get the scrub typhus IgM antibody test in addition to the tropical fever work up (Malaria antigen, Dengue NS1 antigen, and IgM). Serology for scrub typhus was detected and he was started on doxycycline 100 mg twice a day. His fever and thrombocytopenia resolved in the next 2 days. After a total of 14 days in-hospital management, the patient was discharged successfully.
Figure 1: (a) Chest X-ray (posteroanterior view) of the first patient demonstrating bilateral peripheral lung consolidation. (b) High-resolution computed tomography scan of the first patient demonstrating bilateral ground glass opacities and patchy consolidation

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Figure 2: Bite site eschar mark on the right nipple of the first case

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Case 2

A 42-year-old female came to the emergency room with the complaints of breathlessness from the past 6 days, along with fever from past 2 days. The patient was a known case of hypertension for last 3 years and was taking oral ramipril 5 mg once a day. She had no concurrent chest pain, palpitations, lower limb swelling, or decreased urine output. At presentation, her blood pressure was 126/82 mm Hg, plasma glucose was 86 mg/dl and SpO2 under RA was 87%. She was afebrile and supplemented of O2 at 6 L/min with VM improved her SpO2 to 94%. The patient had a normal ECG but the chest roentgen-graph demonstrated bilateral peripheral haziness [Figure 3]. Due to ongoing pandemic, the patient was tested for COVID-19 and found positive by RT-PCR. Initially, she was started on injectable steroids (dexamethasone 6 mg once a day) only as her CBC demonstrated thrombocytopenia (96 × 109/L, normal 150–450). Inflammatory markers in this patient depicted d-dimer levels of 0.7 μg/mL (normal <0.5), serum ferritin of 708 ng/mL (normal 10–219 for female), IL-6 of 11.9 pg/mL (normal 4–12), and CRP of 21 mg/L (normal <5). Despite persistent low platelet counts, her SpO2 improved and she was off O2 by day 7. Further, she was evaluated for autoimmune disorders, but had normal anti-nuclear antibody, rheumatoid factor, and anti-double stranded deoxyribonucleic acid levels. Her ultrasound of the abdomen was inconclusive except for the splenomegaly of 14.6 cm. Thrombocytopenia with splenomegaly raised the possibility of tropical fever illnesses and she was evaluated for commonly encountered tropical diseases (i.e., malaria, dengue, and scrub typhus). Surprisingly, her IgM antibody was positive for only scrub typhus and she was started on doxycycline 100 mg twice a day. Her platelet counts demonstrated improvement by day 3 and she was discharged on the same antibiotic.
Figure 3: Chest X-ray (anteroposterior view) of the second patient demonstrating peripheral lung opacities bilaterally

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  Discussion Top


Endemic regions for tropical diseases such as Malaria, Dengue, Scrub typhus, Leptospirosis, and Chikungunya have a large potential to convert COVID-19 pandemic into a co-infection epidemic. For example, Hazra et al. reported a case of COVID-19 and Scrub typhus in a 70-year-old female from India.[3] Similarly, Sardar et al. described a case of Malaria with COVID-19 from Qatar, and Malibari et al. demonstrated Dengue virus and COVID-19 co-infection in Saudi Arabia.[4],[5] All these cases were from the endemic countries for tropical diseases and delineate the impending co-infection burden in the COVID-19 era.

Diseases such as scrub typhus and COVID-19 have a vast clinical spectrum, making these infections impossible to diagnose clinically. Fever, skin rash, malaise, headache, acute respiratory distress, and thrombocytopenia are some clinical features which can be shared by both the diseases. In the presence of these relatively common but nonspecific manifestations, the diagnosis of co-infection can be readily missed, leading to an unfavorable outcome. Both of the patients in our report had respiratory distress and thrombocytopenia, which can be encountered in both scrub typhus and COVID-19. Skin eschar, which is specific for scrub typhus, is found 7%–80% of the cases but can be easily overlooked.[2] Moreover, thrombocytopenia can be seen in other infections also and does not point out the specific cause. However, persistently low platelet count can favor the alternative diagnosis as confronted in our cases.

The pathophysiology of thrombocytopenia in tropical fever diseases includes imbalance between platelet production and clearance, interaction between pathogen or secreted molecule and platelet surface receptors, and platelet sequestration due to endothelial dysfunction or immune activation.[6] These factors can lead to thrombocytopenia and sometimes, thrombocytosis. Whereas, in COVID-19, thrombocytopenia occurs due to decreased platelet production by bone marrow (bone marrow progenitor cell apoptosis) and increased platelet destruction (due to binding of viral epitope to the platelets and complement activation against this complex).[1] Further, a recent research, including 1476 individuals with COVID-19 concluded low platelet count as a poor prognostic marker as thrombocytopenia was associated with increased mortality in these patients. Similarly, in a study including 365 scrub typhus patients, thrombocytopenia (<100,000 platelets/mm3) was correlated with increased bleeding and severe disease.[7] Noninfectious causes like immune thrombocytopenic purpura, connective tissue disorders like systemic lupus erythematosus and rheumatoid arthritis, leukemia like malignancies and drugs or heparin-related thrombocytopenia should also be considered, which can be unmasked during COVID-19 evaluation.

Other than thrombocytopenia, respiratory distress was also experienced by our patients and has been described in the context of both scrub typhus and COVID-19 infection. Distinguishing feature can be pattern of lung parenchymal involvement. In COVID-19, peripheral parts of lung fields are more commonly involved in the form of consolidation and ground glass opacities.[8] Whereas in acute respiratory distress of scrub typhus, central part is more frequently entangled in the form of reticulonodular opacities, interlobular septal, and axial interstitial thickening.[9] Our patients had peripheral lung involvement, which favors COVID-19 infection as a causal factor for respiratory distress more than the scrub typhus but this conclusion may be inaccurate.

The diagnosis of both these infections is straightforward if the index of suspicion is high. COVID-19 can be diagnosed easily with RT-PCR of nasopharyngeal or oro-pharyngeal swab. Real-time RT-PCR (rRT-PCR) and reverse transcription loop-mediated isothermal amplification are other new tests with better specificity, but these viral practical detecting investigations are less sensitive than the chest CT scan.[10] On the other hand, scrub typhus is diagnosed predominantly with serological tests. The indirect immunofluorescence assay is the gold standard in this context, but enzyme-linked immunosorbent assay detecting IgM antibodies is most widely used investigation with a sensitivity and specificity of 93% and 97%, respectively.[2] The management differs for both these co-infections. Steroids and anti-coagulation drugs like low molecular-weight heparin constitute the cornerstone of COVID-19 management.[10] Whereas, doxycycline, azithromycin, and rifampicin are commonly used drugs for scrub typhus infection. Among these, doxycycline 100 mg twice a day is the drug of choice and available in both oral and injectable forms. Surprisingly, this drug is also useful in COVID-19 by inhibiting viral serine protease and replication.[11]


  Conclusion Top


Scrub typhus and COVID-19 can infect a person simultaneously and the co-infection should not be missed in the era of this pandemic. The subtle signs of co-infections may be a persistent fever or rash, leukocytosis or thrombocytopenia, or an atypical radiographic appearance. A low threshold for tropical fever investigations is advisable in this setting for timely diagnosis and favorable outcome. As both of the infections have different management strategies, judicious use of anticoagulant is preferable in this milieu to avoid bleeding manifestations. Further, doxycycline, which is a drug of choice for scrub typhus, can be beneficial in COVID-19 too, and should be added in the treatment of high risk individual.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for 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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Mina A, van Besien K, Platanias LC. Hematological manifestations of COVID-19. Leuk Lymphoma 2020;61:2790-8.  Back to cited text no. 1
    
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Gaba S, Gupta M, Gaba R, Lehl SS. Scrub typhus: An update. Curr Trop Med Rep 2021;8:133-40.  Back to cited text no. 2
    
3.
Hazra D, Abhilash KP, Gunasekharan K, Prakash JA. Eschar: An indispensable clue for the diagnosis of scrub typhus and COVID-19 co-infection during the ongoing pandemic. J Postgrad Med 2021;67:117-8.  Back to cited text no. 3
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Sardar S, Sharma R, Alyamani TY, Aboukamar M. COVID-19 and Plasmodium vivax malaria co-infection. IDCases 2020;21:e00879.  Back to cited text no. 4
    
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Malibari AA, Al-Husayni F, Jabri A, Al-Amri A, Alharbi M. A patient with dengue fever and COVID-19: Coinfection or not? Cureus 2020;12:e11955.  Back to cited text no. 5
    
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Hapsari Putri I, Tunjungputri RN, De Groot PG, van der Ven AJ, de Mast Q. Thrombocytopenia and platelet dysfunction in acute tropical infectious diseases. Semin Thromb Hemost 2018;44:683-90.  Back to cited text no. 6
    
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Lee HJ, Park CY, Park SG, Yoon NR, Kim DM, Chung CH. Activation of the coagulation cascade in patients with scrub typhus. Diagn Microbiol Infect Dis 2017;89:1-6.  Back to cited text no. 7
    
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Bernheim A, Mei X, Huang M, Yang Y, Fayad ZA, Zhang N, et al. Chest CT findings in coronavirus disease-19 (COVID-19): Relationship to duration of infection. Radiology 2020;295:200463.  Back to cited text no. 8
    
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Jeong YJ, Kim S, Wook YD, Lee JW, Kim KI, Lee SH. Scrub typhus: Clinical, pathologic, and imaging findings. Radiographics 2007;27:161-72.  Back to cited text no. 9
    
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Zhai P, Ding Y, Wu X, Long J, Zhong Y, Li Y. The epidemiology, diagnosis and treatment of COVID-19. Int J Antimicrob Agents 2020;55:105955.  Back to cited text no. 10
    
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Sodhi M, Etminan M. Therapeutic potential for tetracyclines in the treatment of COVID-19. Pharmacotherapy 2020;40:487-8.  Back to cited text no. 11
    


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  [Figure 1], [Figure 2], [Figure 3]



 

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