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Myocarditis Following Recent Chikungunya and Dengue Virus Coinfection: A Case Report

Keywords
Myocarditis; Coinfection; Dengue; Chikungunya Virus

Introduction

Dengue virus (DENV) and chikungunya virus (CHIKV) are arboviruses that cause ongoing epidemics in several countries of Latin America. DENV belongs to the Flaviviridae family and CHIKV is an alphavirus of the Togaviridae family. Both viruses are transmitted by mosquitoes of the genus Aedes (mainly Aedes aegypti and Aedes albopictus) and during the acute phase they may cause similar nonspecific febrile syndromes that can progress to severe or debilitating conditions.11 Mayer SV, Tesh RB, Vasilakis N. The emergence of arthropod-borne viral diseases: A global prospective on dengue, chikungunya and zika fevers. Acta Tropica. 2017 Feb;166:155-63.,22 Pierson TC, Diamond MS. Flaviviruses. In: Knipe DM, Howley PM, Cohen IC (eds). 6th ed. Fields virology. Philadelphia: Wolters Kluwer, 2014.p.746-94.

DENV infection has been endemic in Brazil since the 1980's. However, CHIKV is an emergent agent. Autochthonous transmission was first detected in September 2014 in the city of Oiapoque, Amapá state. Since then, there have been thousands of autochthonous cases in the country.33 Donalisio M, Freitas A, Zuben A. Arboviruses emerging in Brazil: challenges for clinic and implications for public health. Rev Saude Publica. 2017 Apr;51:30. A total of 38,499 and 277,882 cases of suspected CHIKV infection were reported by the national surveillance system in 2015 and 2016, respectively. In 2017, a total of 185,369 suspected cases were reported until December 9. Ceará (1,271 cases/100,000 inhabitants) and Roraima (789 cases/100,000 inhabitants) have the highest incidence among the Brazilian Federation states.44 Brasil. Ministério da Saúde. Secretaria de Vigilância Sanitária. Monitoramento dos casos de dengue , febre chikungunya e febre pelo vírus Zika. Boletim Epidemiológico. 2017;48(44):1-13. Coinfections with these two viruses have been reported and the overall effect on the heart is still unknown.55 Furuya-Kanamori L, Liang S, Milinovich G, Magalhaes RJS, Clements ACA, Hu W, et al. Co-distribution and co-infection of chikungunya and dengue viruses. BMC Infectious Diseases. 2016 Mar;16:84.

6 Alvarez MF, Bolívar-Mejía A, Rodriguez-Morales AJ, Ramirez-Vallejo E. Cardiovascular involvement and manifestations of systemic Chikungunya virus infection: A systematic review. F1000Res. 2017;6:390.
-77 Shivanthan M, Navinan M, Constantine G, Rajapakse S. Cardiac involvement in dengue infection. J Infect Dev Ctries. 2015;9(4):338-346. There have been some reports of myopericarditis following DENV and CHIKV infection, but this manifestation in coinfected patients is rare and few data are available.88 Ramanathan K, Teo L, Raymond W, MacLaren G. Dengue Myopericarditis Mimicking Acute Myocardial Infarction. Circulation. 2015;131(23):519-22.

9 Simon F, Paule P, Oliver M. Chikungunya virus-induced myopericarditis: toward an increase of dilated cardiomyopathy in countries with epidemics? Am J Trop Med Hyg. 2008;78(2):212-3.
-1010 Maiti CR, Mukherjee AK, Bose B, Saha GL. Myopericarditis following chikungunya virus infection. J Indian Med Assoc. 1978;70(11):256-8.

The aim of this report is to present a case of a young and immunocompetent man with myocarditis, following a recent DENV and CHIKV coinfection. We discuss the clinical course and laboratory abnormalities of this rare condition, along with its successful management in an infectious disease specialized center, highlighting the importance of being aware of this condition in developing countries endemic for DENV and CHIKV.

Case report

The patient was a 28-year-old male, resident in Fortaleza, Ceará State and was admitted in the emergency room of São José Hospital of Infectious Diseases in May 2017. The symptoms had started 5 days prior to admission with fever, adynamia, myalgia, and worsening of general condition. He denied retroorbital pain, bleeding phenomena or abdominal pain. He had taken no medications in the previous year and had not traveled outside of Brazil. There was no previous history of cardiopathies.

Upon the initial examination, the Glasgow Coma Scale (GCS) score of the patient was E4 V5 M6. He had a heart rate of 120 beats per minute and had hypotension (70/40 mm of Hg). There was no heart murmur or pericardial rub and his pulmonary examination was unremarkable. The skin showed no rashes, and there were no petechiae or jaundice.

The electrocardiogram (EKG) showed supraventricular tachycardia (230 bpm) not responsive to intravenous adenosine. An electric cardioversion was performed and successfully restored the normal heart rhythm. A new EKG was performed showing ST elevation with upper concavity and PR segment depression in DII, DIII and aVF, such as ST depression in V1 and aVR. The patient was then admitted to the intensive care unit. His laboratory parameters are described in Table 1. A first transthoracic echocardiogram revealed an altered left ventricular ejection fraction (EF) (43%), left ventricular hypercontractility, and mild bilateral pericardial and pleural effusions (Figure 1). After 5 days, a new echocardiogram was performed, revealing a 36.4% EF, as well as diffuse hypokinesia and moderate pericardial effusion.

Table 1
Laboratory results during hospital stay of a patient with myocarditis and coinfection with dengue virus and Chikungunya virus

Figure 1
Transthoracic echocardiogram with altered left ventricular ejection fraction (36.39%), left ventricular hypercontractility, and mild bilateral pericardial effusion (A-D). E-H shows a second transthoracic echocardiogram with ejection fraction of 70%. DP and LP: pericardial effusion. RV: right ventricle; LV: left ventricle; RA: right atrium; LA: left atrium; EF: ejection fraction.

Dobutamine (2.9 mcg/Kg/min) IV was initiated and maintained for 4 days and a single dose of 400 mg of hydrocortisone IV was administered. Treatments with immunoglobulin IV or colchicine were not considered. Paired blood cultures were negative for pyogenic agents. Antibiotics were not used.

Serologies for coxsackie virus, rubella, Chagas disease, human immunodeficiency virus, cytomegalovirus, Epstein-Barr virus (EBV), toxoplasmosis, hepatitis B virus and hepatitis C virus were negative. The patient’s serum samples were tested and found to be ELISA-IgM positive and ELISA-IgG positive for DENV and ELISA-IgM positive for CHIKV. The DENV NS1 antigen test yielded a negative result. There was a good response to therapy and the patient progressed with gradual improvement until recovery of ventricular function. After 11 days, a last echocardiogram showed an EF of 70% and persistence of pericardial effusion. The patient was discharged from the hospital 11 days after admission. Table 1 shows laboratory results during hospital stay.

Discussion

Typical clinical manifestations of acute CHIKV infection are fever, headache, polyarthralgia/polyarthritis, myalgia, rash, and fatigue.1111 Cunha RVD, Trinta KS. Chikungunya virus: clinical aspects and treatment - A Review. Mem Inst Oswaldo Cruz. 2017;112(8): 523-31. Atypical manifestations have also been described, affecting the cardiovascular, nervous, ocular, cutaneous, and other systems.66 Alvarez MF, Bolívar-Mejía A, Rodriguez-Morales AJ, Ramirez-Vallejo E. Cardiovascular involvement and manifestations of systemic Chikungunya virus infection: A systematic review. F1000Res. 2017;6:390.,1212 Brizzi K. Neurologic Manifestation of Chikungunya Virus. Curr Infect Dis Rep. 2017;19(2):6.

13 Mahendradas P, Avadhani K, Shetty R. Chikungunya and the eye: a review. J Ophthalmic Inflamm Infect. 2013;3(1):35.
-1414 Bandyopadhyay D, Ghosh SK. Mucocutaneous manifestations of Chikungunya fever. Indian J Dermatol. 2010;55(1):64-7. The clinical spectrum of chikungunya heart disease ranges from asymptomatic ECG alterations to potentially lethal cardiac complications.66 Alvarez MF, Bolívar-Mejía A, Rodriguez-Morales AJ, Ramirez-Vallejo E. Cardiovascular involvement and manifestations of systemic Chikungunya virus infection: A systematic review. F1000Res. 2017;6:390.

The manifestations of acute DENV infection are very similar to those of CHIKV, with a lower prevalence for joint manifestations.1515 Simmons CP, Farrar JJ, Nguyen VV, Wills B. Dengue. N Engl J Med. 2012;366(15):1423-32. Heart involvement in DENV infection is not uncommon. Cardiac manifestations can vary widely, from silent disease to severe myocarditis resulting in death.77 Shivanthan M, Navinan M, Constantine G, Rajapakse S. Cardiac involvement in dengue infection. J Infect Dev Ctries. 2015;9(4):338-346. Arora et al.77 Shivanthan M, Navinan M, Constantine G, Rajapakse S. Cardiac involvement in dengue infection. J Infect Dev Ctries. 2015;9(4):338-346. studying 120 patients with DENV found 37.5% of patients with cardiac manifestation in the form of myocarditis and 5% with rhythm disturbance, with AV block being the most common.1616 Arora M, Patil RS. Cardiac Manifestation in Dengue Fever. J Assoc Physicians India. 2016;64(7):40-4.

The specific viral diagnosis is commonly made through ELISA, a specific serological test.1111 Cunha RVD, Trinta KS. Chikungunya virus: clinical aspects and treatment - A Review. Mem Inst Oswaldo Cruz. 2017;112(8): 523-31.,1515 Simmons CP, Farrar JJ, Nguyen VV, Wills B. Dengue. N Engl J Med. 2012;366(15):1423-32. In cases of DENV, secretion of the NS1 non-structural viral protein from infected cells makes an early diagnosis possible. NS1 protein can be detected in blood and tissue samples within 9 days of the onset of fever.1515 Simmons CP, Farrar JJ, Nguyen VV, Wills B. Dengue. N Engl J Med. 2012;366(15):1423-32.

There is a low probability that the patient had an isolated viral infection since both viruses are part of different viral families, thus considerably reducing the cross-reaction probability. Kam et al.1717 Kam YH, Pok KY, Eng KE, Tan LK, Kaur S, Lee WW, et al. Sero-Prevalence and Cross-Reactivity of Chikungunya Virus Specific Anti-E2EP3 Antibodies in Arbovirus-Infected Patients. PLoS Negl Trop Dis. 2015;9(1):e3445. found that 6% of DENV-infected patients had antibodies that were cross-reactive to CHIKV.1717 Kam YH, Pok KY, Eng KE, Tan LK, Kaur S, Lee WW, et al. Sero-Prevalence and Cross-Reactivity of Chikungunya Virus Specific Anti-E2EP3 Antibodies in Arbovirus-Infected Patients. PLoS Negl Trop Dis. 2015;9(1):e3445. Although they share the same vector, CHIKV is part of the Togaviridae family, while DENV is part of the Flaviviridae family.

Heart disease associated with arboviruses has no specific treatment and may be a self-limited condition. Thus, quick supportive therapy to prevent further cardiac function loss and cardiogenic shock is still the most recommended management.66 Alvarez MF, Bolívar-Mejía A, Rodriguez-Morales AJ, Ramirez-Vallejo E. Cardiovascular involvement and manifestations of systemic Chikungunya virus infection: A systematic review. F1000Res. 2017;6:390. There is also evidence that IV hydrocortisone may be helpful to accomplish full recovery in DENV myocarditis1818 Wiwanitkit V. Dengue myocarditis, rare but not fatal manifestation. Int J Cardiol. 2006;112(1):122. but there is yet no consensus about whether this drug should be used in this setting or if it has a real impact on recovery and mortality rates, even more in cases of combined arbovirus infection. Although arbovirus myocarditis is an acute condition, most patients persist chronically with cardiac disease, such as chronic heart failure and ECG T-wave changes.1616 Arora M, Patil RS. Cardiac Manifestation in Dengue Fever. J Assoc Physicians India. 2016;64(7):40-4.,1919 Obeyesekere I, Hermon Y. Arbovirus heart disease: myocarditis and cardiomyopathy following dengue and chikungunya fever--a follow-up study. Am Heart J. 1973;85(2):186-94. The role of coinfection in the severity of arbovirus cardiac manifestations is not currently known, but studies regarding other symptoms showed that it might contribute to a more severe disease.66 Alvarez MF, Bolívar-Mejía A, Rodriguez-Morales AJ, Ramirez-Vallejo E. Cardiovascular involvement and manifestations of systemic Chikungunya virus infection: A systematic review. F1000Res. 2017;6:390.,77 Shivanthan M, Navinan M, Constantine G, Rajapakse S. Cardiac involvement in dengue infection. J Infect Dev Ctries. 2015;9(4):338-346.,2020 Mukherjee S, Dutta SK, Sengupta S, Tripathi A. Evidence of dengue and chikungunya virus co-infection and circulation of multiple dengue serotypes in a recent Indian outbreak. Eur J Clin Microbiol Infect Dis. 2017;36(11):2273-9. It is also noteworthy that the herein described myocarditis may have been caused solely by the CHIKV, since the NS1 protein test yielded a negative result. It is also important to note that the DENV IgM may be positive from 139 up to 179 days, respectively for secondary and primary infections.2121 Prince HE, Matud JL. Estimation of Dengue Virus IgM Persistence Using Regression Analysis. Clin Vaccine Immunol. 2011;18(12):2183-5.

The present study has limitations. Polymerase chain reaction (PCR) was not available for the etiological diagnosis. The degree of myocardial impairment was not assessed by Magnetic Resonance Imaging (MRI). Although reported by other authors,88 Ramanathan K, Teo L, Raymond W, MacLaren G. Dengue Myopericarditis Mimicking Acute Myocardial Infarction. Circulation. 2015;131(23):519-22.,99 Simon F, Paule P, Oliver M. Chikungunya virus-induced myopericarditis: toward an increase of dilated cardiomyopathy in countries with epidemics? Am J Trop Med Hyg. 2008;78(2):212-3. MRI was not available at our center.

Conclusion

The case presented herein suggests that DENV and CHIKV coinfection may result in myocarditis, which can be severe and may be possibly reverted with supportive therapy and correct management of cardiac function. Nevertheless, the correct etiopathogenesis of the cardiac disorder is undefined and the disease may be caused solely by either the DENV or CHIKV virus. It is important to be aware of this possible complication of arboviruses mainly in endemic areas.

  • Sources of Funding
    There were no external funding sources for this study.
  • Study Association
    This study is not associated with any thesis or dissertation work.
  • Ethics approval and consent to participate
    This study was approved by the Ethics Committee of the Hospital de São José de Doenças Infecciosas under the protocol number 2.405.527. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013.

References

  • 1
    Mayer SV, Tesh RB, Vasilakis N. The emergence of arthropod-borne viral diseases: A global prospective on dengue, chikungunya and zika fevers. Acta Tropica. 2017 Feb;166:155-63.
  • 2
    Pierson TC, Diamond MS. Flaviviruses. In: Knipe DM, Howley PM, Cohen IC (eds). 6th ed. Fields virology. Philadelphia: Wolters Kluwer, 2014.p.746-94.
  • 3
    Donalisio M, Freitas A, Zuben A. Arboviruses emerging in Brazil: challenges for clinic and implications for public health. Rev Saude Publica. 2017 Apr;51:30.
  • 4
    Brasil. Ministério da Saúde. Secretaria de Vigilância Sanitária. Monitoramento dos casos de dengue , febre chikungunya e febre pelo vírus Zika. Boletim Epidemiológico. 2017;48(44):1-13.
  • 5
    Furuya-Kanamori L, Liang S, Milinovich G, Magalhaes RJS, Clements ACA, Hu W, et al. Co-distribution and co-infection of chikungunya and dengue viruses. BMC Infectious Diseases. 2016 Mar;16:84.
  • 6
    Alvarez MF, Bolívar-Mejía A, Rodriguez-Morales AJ, Ramirez-Vallejo E. Cardiovascular involvement and manifestations of systemic Chikungunya virus infection: A systematic review. F1000Res. 2017;6:390.
  • 7
    Shivanthan M, Navinan M, Constantine G, Rajapakse S. Cardiac involvement in dengue infection. J Infect Dev Ctries. 2015;9(4):338-346.
  • 8
    Ramanathan K, Teo L, Raymond W, MacLaren G. Dengue Myopericarditis Mimicking Acute Myocardial Infarction. Circulation. 2015;131(23):519-22.
  • 9
    Simon F, Paule P, Oliver M. Chikungunya virus-induced myopericarditis: toward an increase of dilated cardiomyopathy in countries with epidemics? Am J Trop Med Hyg. 2008;78(2):212-3.
  • 10
    Maiti CR, Mukherjee AK, Bose B, Saha GL. Myopericarditis following chikungunya virus infection. J Indian Med Assoc. 1978;70(11):256-8.
  • 11
    Cunha RVD, Trinta KS. Chikungunya virus: clinical aspects and treatment - A Review. Mem Inst Oswaldo Cruz. 2017;112(8): 523-31.
  • 12
    Brizzi K. Neurologic Manifestation of Chikungunya Virus. Curr Infect Dis Rep. 2017;19(2):6.
  • 13
    Mahendradas P, Avadhani K, Shetty R. Chikungunya and the eye: a review. J Ophthalmic Inflamm Infect. 2013;3(1):35.
  • 14
    Bandyopadhyay D, Ghosh SK. Mucocutaneous manifestations of Chikungunya fever. Indian J Dermatol. 2010;55(1):64-7.
  • 15
    Simmons CP, Farrar JJ, Nguyen VV, Wills B. Dengue. N Engl J Med. 2012;366(15):1423-32.
  • 16
    Arora M, Patil RS. Cardiac Manifestation in Dengue Fever. J Assoc Physicians India. 2016;64(7):40-4.
  • 17
    Kam YH, Pok KY, Eng KE, Tan LK, Kaur S, Lee WW, et al. Sero-Prevalence and Cross-Reactivity of Chikungunya Virus Specific Anti-E2EP3 Antibodies in Arbovirus-Infected Patients. PLoS Negl Trop Dis. 2015;9(1):e3445.
  • 18
    Wiwanitkit V. Dengue myocarditis, rare but not fatal manifestation. Int J Cardiol. 2006;112(1):122.
  • 19
    Obeyesekere I, Hermon Y. Arbovirus heart disease: myocarditis and cardiomyopathy following dengue and chikungunya fever--a follow-up study. Am Heart J. 1973;85(2):186-94.
  • 20
    Mukherjee S, Dutta SK, Sengupta S, Tripathi A. Evidence of dengue and chikungunya virus co-infection and circulation of multiple dengue serotypes in a recent Indian outbreak. Eur J Clin Microbiol Infect Dis. 2017;36(11):2273-9.
  • 21
    Prince HE, Matud JL. Estimation of Dengue Virus IgM Persistence Using Regression Analysis. Clin Vaccine Immunol. 2011;18(12):2183-5.

Publication Dates

  • Publication in this collection
    23 Sept 2019
  • Date of issue
    Oct 2019

History

  • Received
    30 June 2018
  • Reviewed
    06 Oct 2018
  • Accepted
    17 Oct 2018
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