Idiopathic acute myocarditis during treatment for controlled human malaria infection: a case report

A 23-year-old healthy male volunteer took part in a clinical trial in which the volunteer took chloroquine chemoprophylaxis and received three intradermal doses at four-week intervals of aseptic, purified Plasmodium falciparum sporozoites to induce protective immunity against malaria. Fifty-nine days after the last administration of sporozoites and 32 days after the last dose of chloroquine the volunteer underwent controlled human malaria infection (CHMI) by the bites of five P. falciparum-infected mosquitoes. Eleven days post-CHMI a thick blood smear was positive (6 P. falciparum/μL blood) and treatment was initiated with atovaquone/proguanil (Malarone®). On the second day of treatment, day 12 post-CHMI, troponin T, a marker for cardiac tissue damage, began to rise above normal, and reached a maximum of 1,115 ng/L (upper range of normal = 14 ng/L) on day 16 post-CHMI. The volunteer had one ~20 minute episode of retrosternal chest pain and heavy feeling in his left arm on day 14 post-CHMI. ECG at the time revealed minor repolarization disturbances, and cardiac MRI demonstrated focal areas of subepicardial and midwall delayed enhancement of the left ventricle with some oedema and hypokinesia. A diagnosis of myocarditis was made. Troponin T levels were normal within 16 days and the volunteer recovered without clinical sequelae. Follow-up cardiac MRI at almost five months showed normal function of both ventricles and disappearance of oedema. Delayed enhancement of subepicardial and midwall regions decreased, but was still present. With the exception of a throat swab that was positive for rhinovirus on day 14 post-CHMI, no other tests for potential aetiologies of the myocarditis were positive. A number of possible aetiological factors may explain or have contributed to this case of myocarditis including, i) P. falciparum infection, ii) rhinovirus infection, iii) unidentified pathogens, iv) hyper-immunization (the volunteer received six travel vaccines between the last immunization and the CHMI), v) atovaquone/proguanil treatment, or vi) a combination of these factors. Definitive aetiology and pathophysiological mechanism for the myocarditis have not been established.

[1]  D. Le Guludec,et al.  Myocarditis in patients with clinical presentation of myocardial infarction and normal coronary angiograms. , 2001, Journal of the American College of Cardiology.

[2]  G. Thiene,et al.  Myocarditis and inflammatory cardiomyopathy: microbiological and molecular biological aspects. , 2003, Cardiovascular research.

[3]  A. D. de Bold,et al.  Angiotensin II receptor antagonism reverts the selective cardiac BNP upregulation and secretion observed in myocarditis. , 2008, American journal of physiology. Heart and circulatory physiology.

[4]  S. Hoffman,et al.  Safety and clinical outcome of experimental challenge of human volunteers with Plasmodium falciparum-infected mosquitoes: an update. , 2007, The Journal of infectious diseases.

[5]  R. Kim,et al.  Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies. , 2005, European heart journal.

[6]  Mario Roederer,et al.  Protection Against Malaria by Intravenous Immunization with a Nonreplicating Sporozoite Vaccine , 2013, Science.

[7]  Georgios Giannopoulos,et al.  NTproBNP: an important biomarker in cardiac diseases. , 2013, Current topics in medicinal chemistry.

[8]  S L Hoffman,et al.  Clinical manifestations of Plasmodium falciparum malaria experimentally induced by mosquito challenge. , 1997, The Journal of infectious diseases.

[9]  D. Barceloux,et al.  Medical toxicology: Diagnosis and treatment of human poisoning , 1988 .

[10]  S. Hoffman,et al.  Controlled Human Malaria Infections by Intradermal Injection of Cryopreserved Plasmodium falciparum Sporozoites , 2013, The American journal of tropical medicine and hygiene.

[11]  C. Mengoli,et al.  Fatal Myocarditis in Course of Plasmodium falciparum Infection: Case Report and Review of Cardiac Complications in Malaria , 2011, Case reports in medicine.

[12]  S. Hoffman,et al.  Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe , 2013, PloS one.

[13]  T. Jelínek,et al.  Fatal Malaria in a German Couple Returning from Burkina Faso , 2003, Infection.

[14]  R. Sauerwein,et al.  Cardiac complication after experimental human malaria infection: a case report , 2009, Malaria Journal.

[15]  H. Rotbart Human enterovirus infections. , 1995 .

[16]  T. Bousema,et al.  Clinical outcome of experimental human malaria induced by Plasmodium falciparum-infected mosquitoes. , 2005, The Netherlands journal of medicine.

[17]  M. Sanklecha,et al.  Chronic pancreatic insufficiency-think of Shwachmann Diamond Syndrome. , 2012, Indian pediatrics.

[18]  T. Martino,et al.  Enteroviral Myocarditis and Dilated Cardiomyopathy: a Review of Clinical and Experimental Studies , 1995 .

[19]  S. Green,et al.  Myocarditis associated with Plasmodium falciparum malaria: a case report and a review of the literature. , 2006, Journal of travel medicine.

[20]  E. Otten Ellenhorn's medical toxicology: Diagnosis and treatment of human poisoning, 2nd ed , 1997 .

[21]  G. C. Rodgers Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning , 1997 .

[22]  M. Sanklecha,et al.  Varied presentation of complicated falciparum malaria in a family. , 2012, Indian pediatrics.

[23]  N. White,et al.  Short report: no evidence of cardiotoxicity of atovaquone-proguanil alone or in combination with artesunate. , 2005, The American journal of tropical medicine and hygiene.

[24]  Matthias Gutberlet,et al.  Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper , 2009 .

[25]  F. Adams,et al.  Letter: Supraventricular tachycardia in an infant associated with a rhinoviral infection. , 1975, The Journal of pediatrics.

[26]  R. Sauerwein,et al.  Experimental human challenge infections can accelerate clinical malaria vaccine development , 2010, Nature Reviews Immunology.

[27]  Y. Finkelstein,et al.  Eosinophilic Myocarditis Temporally Associated With Conjugate Meningococcal C and Hepatitis B Vaccines in Children , 2008, The Pediatric infectious disease journal.

[28]  C. Visser,et al.  Frequent Detection of Respiratory Viruses without Symptoms: Toward Defining Clinically Relevant Cutoff Values , 2011, Journal of Clinical Microbiology.

[29]  S. Hoffman,et al.  Malaria transmitted to humans by mosquitoes infected from cultured Plasmodium falciparum. , 1986, The American journal of tropical medicine and hygiene.

[30]  M. Dietrich,et al.  [Fatal complications of tropical malaria in non-immune patients. A retrospective clinico-pathologic analysis of 25 cases]. , 2008, Deutsche medizinische Wochenschrift.

[31]  E. R. James,et al.  Live Attenuated Malaria Vaccine Designed to Protect Through Hepatic CD8+ T Cell Immunity , 2011, Science.

[32]  R. Sauerwein,et al.  Long-term protection against malaria after experimental sporozoite inoculation: an open-label follow-up study , 2011, The Lancet.

[33]  J. Doherty,et al.  Short report: hematologic changes in acute, imported Plasmodium falciparum malaria. , 1998, The American journal of tropical medicine and hygiene.

[34]  K. Klingel,et al.  Presentation, Patterns of Myocardial Damage, and Clinical Course of Viral Myocarditis , 2006, Circulation.

[35]  M. Grobusch,et al.  Myocardial damage in falciparum malaria detectable by cardiac troponin T is rare , 2003, Tropical medicine & international health.

[36]  N. Brattig,et al.  High levels of circulating cardiac proteins indicate cardiac impairment in African children with severe Plasmodium falciparum malaria. , 2005, Microbes and infection.

[37]  W. Nahorski,et al.  Severe malaria--analysis of prognostic symptoms and signs in 169 patients treated in Gdynia in 1991-2005. , 2006, International maritime health.

[38]  Mooweon Rhee,et al.  A case of myocarditis associated with Plasmodium vivax malaria. , 2009, Journal of travel medicine.

[39]  Adrian J F Luty,et al.  Protection against a malaria challenge by sporozoite inoculation. , 2009, The New England journal of medicine.

[40]  J. Mason,et al.  Advances in the understanding of myocarditis. , 2001, Circulation.

[41]  J. Banatvala Viral infections of the heart , 1993 .