Research & Grants

FAQ of Types of Viruses and Bacteria that Cause Myocarditis

Monte Willis, MD, PhD, FASCP, FCAPWritten By Monte Willis MD, PhD, FASCP, FCAP

What are known infectious diseases that have been linked to causing myocarditis?

A:  A wide variety of infectious diseases can result in myocarditis, including viruses, bacteria, chlamydia, rickettsia, fungi, and protozoa.  Viruses are most often the infectious disease found to cause acute myocarditis.

What viruses are related to the development of myocarditis?

A:  The cause of myocarditis was originally determined in experimental and epidemiological studies in the 1950s and 1960s by investigating myocarditis patients’ antibody responses to disease, indicating that they had been exposed to them.  These studies found that enteroviruses, including Coxsackie viruses were present in myocarditis patients 1,2.  With increasingly powerful ways to identify infectious diseases using molecular techniques in the 1980s, other viruses were also found in association with myocarditis 3,4.  Most frequently, the following viruses are found in the hearts of myocarditis patients:

  • Parvovirus B19
  • Human Herpes Virus 6
  • Enterovirus (Coxsackie Virus).

These types of studies identifying the causes of myocarditis are rarely done in many parts of the world including South America, the Middle East, Asia, and Africa, so the prevalence in those regions hasn’t been determined.

What are Parvovirus B19, Human Herpes Virus 6, and Enteroviruses?

A:  Parvovirus B19 is the virus that causes “fifth disease”, also referred to as “slapped check syndrome” most commonly seen in children 6-10 years old.  It is spread primarily by exposure to an infected person’s respiratory droplets (e.g. by coughing).  Symptoms occur approximately one week after exposure and they generally last for a week.  While children generally get the “slapped cheek” appearance (rash), teenagers and young adults develop this rash in other areas of the body, including the hands and feet.  In adults, Parvovirus B19 has been associated with infections in patients with AIDs, arthritis, aplastic anemia (lack of red cell production), and severe birth defects and miscarriages during pregnancy.  About ½ of the general population have antibodies against B19, suggesting a past infection.  So many people are exposed to parvovirus B19 with no long term sequelae.  Vaccines are not available for Parvovirus B19.

Human herpes 6 virus is relatively “new” virus just recognized in the past decade.  It is generally acquired at an early age (less than 1 month of age in some cases)5.  About 20% of infant visits to the emergency department for fever may be due to HHV-6 6.  Like other Herpes Viruses, most people are infected chronically and it is a virus most people have been exposed to by the age of 13 months 6.  After the initial infection, it lies dormant in the salivary glands and bone marrow for the lifetime of the person.  The virus is shed in the saliva and symptoms include rash and fever.  In children, the disease roseola infantum, also known as 6th disease, has been associated with HHV-6 infection.  Hepatitis and encephalitis has also been associated.  Multiple sclerosis, chronic fatigues syndrome, fibromyalgia, and myocarditis have been associated with HHV-6 infection.

Enteroviruses, specifically Coxsackie Virus, has been associated with myocarditis.   Cocksackie A virus is associated with hand, foot, and mouth disease; Coxsackie B viruses cause relatively mild symptoms, resembling a cold.  Myocarditis (inflammation of the heart), pericarditis (inflammation of the “sack” surrounding the heart), meningitis (inflammation of the spinal cord outer membranes), and pancreatitis (inflammation of the pancreas supplying digestive enzymes) have all been associated with enterovirus infections.  The symptoms generally include a mild rash and nasal/throat infections.

What are the bacteria that have been implicated in myocarditis?

A:  Both Corynebacterium diptheriae and Staphylococcus aureus have been associated with myocarditis.  Both of these bacteria are widely distributed and found in nature and are generally innocuous.

Corynebacterium diptheriae is the bacteria that causes diphtheria, an acute, contagious infection that causes the cells of the tonsils and throat to die, resulting in pseudomembranes to form in the back of the throat.  C. diptheriae occurs primarily in un-immunized school-aged children and in the elderly and immunocompromised.  There are vaccines against diptheriae that are readily available.

Myocarditis caused by Staphylococcus aureus is generally seen in the face of overwhelming bacteria growing in the blood (sepsis).  This used to be a fairly common complication of sepsis before antibiotics were widely available.  Myocarditis caused by S. aureus can result in abscesses (pockets of bacteria/pus) to form on the heart itself.

What are the blood born parasites that have been associated in myocarditis?

A:  A number of tick-borne diseases have been associated with myocarditis, including Borrelia burgdorferi, Ehrlichia species., and Babesia species.  While these names might not be familiar, they are discussed a fair amount in the lay press (In order:  Lyme Disease, Ehrlichiosis, Babesiosis).  These diseases are found primarily in the upper mid-west, northeast, south, and western United States with overlapping distributions.

What is Borrelia burgdorferi?

A:  Borrelia burgdorferi is a tick-borne bacteria that causes Lyme disease.  The reservoir of the parasite, or place it is kept alive, is in mice.  Specific ticks feed off the mice, become infected, and then feed on humans primarily during the warm summer months.  The bacteria infect human blood, where they then continue to grow and sometimes present as a rash.  The symptoms are non-specific and include fatigue, fever, headache, muscle, and joint aches.  If B. burgdorferi spreads throughout the body without treatment (simple antibiotics), it can cause facial palsy (drooping), meningitis (brain infection/inflammation), joint pain, heart palpitations, and myocarditis 7.

What is Ehrlichia?

A:  Ehrlichia species are bacteria that cause Ehrlichiosis.  Ehrlichia bacteria live in a particular type of white blood cell, called monocytes.  In the wild, both mice (the same mice that harbor Lyme disease) and white-tailed deer have this bacteria living in their blood.  Ticks feed on these hosts, become infected, and then infect humans.  The disease often presents with a sudden high fever, fatigue, muscle aches, and headache within a week of having a tick bite.  Many of these cases are self-resolving; others require antibiotic treatment.  In addition to low white cell counts, low platelet counts, anemia, and liver impairment, and kidney failure can occur.  Ehrlichiosis is diagnosed largely on clinical history, including a history of tick bites, fever and symptoms, in addition to laboratory tests that identify the bacteria in white cells.  Ehrlichiosis can be a cause of myocarditis.

What is Babesia?

A:  Babesia species are protozoa that cause babesiosis.  This parasite lives in red blood cells of domestic animals, particularly mice and deer.  The protozoan is spread by ticks, which acquire it during feeding as the red blood cells are taken up by the tick.  The tick then goes on to feed on humans and infect them.  The parasite then undergoes its life cycle in the red blood cells of human.   Approximately 25% of adults and 50% of children infected do not have any symptoms.  Babesiosis can present with flu-like symptoms including irregular fevers, chills, headaches, lethargy, pain, and a general bad “feeling”.  In severe cases, anemia, shortness of breath and jaundice can be seen.  If recognized, the infection can be treated with antibiotics and in severe cases blood transfusions/exchanges can be performed to lower the parasitic load.  Babesiosis can be a cause of myocarditis.

What is Trypanosoma cruzi?

A:  Trypanosoma cruzi infections cause Chagas disease.  Like the previous infectious agent (Babesia) , this small parasite lives in the red blood cells of wild or domestic mammals.  “Kissing bugs”, also known as triatomine bugs, become infected when feeding upon these mammals.  When these bugs subsequently take a meal from a human, general at night in a bed, it defecates, leaving T. cruzi in the feces.  The T. cruzi enters the human host through the bite wound or by being exposed to mucous membranes such as the mouth.   Here they enter red cells, replicate and burst these red ells, and get sucked up by other “Kissing bugs” further infecting other people.  This is a common disease in South America and much rarer in the United States.

Acutely, Chagas disease often goes undetected (often a localized swelling at the site of entry).  After 10-20 years of chronic infection, internal organs, particularly the heart, can be severely affected and manifest as heart failure.  Acute cases are treated with anti-parasitic drugs; effective therapy for chronic cases is not available.  Chagas disease usually causes impairment in the electrical activity of the heart and heart failure.  Development of an immune response to the disease that cross reacts with the heart itself is thought to be involved in the development of myocarditis in some patients.

What are some non-infectious causes of myocarditis?

A:  Both toxins and allergic reactions to drugs have been linked to myocarditis.  Specifically, exposure to alcohol, radiation, and chemicals, such as hydrocarbons and arsenic, have been implicated.  Damage caused by the anti-cancer drug doxorubicin has also been associated with causing myocarditis.  Severe allergic reactions to antibiotics have also been linked to myocarditis, including sulphonamides and penicillin.

How are the infectious diseases associated with myocarditis diagnosed?

A:  Borrelia burgdorferi, Ehrlichia species, and Babesia species are generally diagnosed by clinical suspicion by physicians recognizing the connection between mild symptoms, possible rashes, tick exposure, in areas known to have the disease during the summer months.  However, laboratory tests identifying these can be performed, including blood smears, molecular tests, and serology (looking for antibodies responses specific for these different species).  Similarly, blood smears are generally used to diagnose Trypanosoma cruzi, in the context of exposure to the appropriate “kissing bugs”, sleeping environment, and in the areas known to have this disease.  In the United States, the suspicion of these diseases are generally low, so they are on the whole underdiagnosed because most many people are asymptomatic.

Do these infectious agents always cause myocarditis?

A:  No.  But the exact number of people with these diseases that continue on to myocarditis in not known as large studies investigating this have not been performed.

 

References

  1. de Leeuw N, Melchers WJ, Balk AH, de Jonge N, Galama JM. Study on microbial persistence in end-stage idiopathic dilated cardiomyopathy. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 1999;29:522-5.
  2. Mavrouli MD, Spanakis N, Levidiotou S, et al. Serologic prevalence of coxsackievirus group B in Greece. Viral immunology 2007;20:11-8.
  3. Kuhl U, Pauschinger M, Noutsias M, et al. High prevalence of viral genomes and multiple viral infections in the myocardium of adults with “idiopathic” left ventricular dysfunction. Circulation 2005;111:887-93.
  4. Matsumori A, Matoba Y, Sasayama S. Dilated cardiomyopathy associated with hepatitis C virus infection. Circulation 1995;92:2519-25.
  5. Braun DK, Dominguez G, Pellett PE. Human herpesvirus 6. Clinical microbiology reviews 1997;10:521-67.
  6. Hall CB, Long CE, Schnabel KC, et al. Human herpesvirus-6 infection in children. A prospective study of complications and reactivation. The New England journal of medicine 1994;331:432-8.
  7. Connolly SE, Benach JL. The versatile roles of antibodies in Borrelia infections. Nature reviews Microbiology 2005;3:411-20.
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