Cardiovascular System Infection Cardiovascular system infection: Myocarditis is inflammation of heart muscle (myocardium), that decreases the strength of the heart to pump blood normally. It resembles a heart attack but coronary arteries are not blocked. The definition of myocarditis varies, but the central feature is an infection of the heart, with an inflammatory infiltrate, and damage to the heart muscle, without the blockage of coronary arteries that define a heart attack (myocardial infarction) or other common non-infectious causes. Myocarditis Myocarditis may or may not include death (necrosis) of heart tissue. It may include dilated cardiomyopathy. Dilated cardiomyopathy or DCM is a condition in which the heart becomes weakened and enlarged and cannot pump blood efficiently. The decreased heart function can affect the lungs, liver, and other body systems. Dilated Cardiomyopathy Dilated cardiomyopathy or DCM: Gross pathology of idiopathic cardiomyopathy. Opened left ventricle of heart shows a thickened, dilated left ventricle with subendocardial fibrosis manifested as increased whiteness of endocardium. Myocarditis Myocarditis is associated with an autoimmune reaction. Streptococcal M protein and coxsackievirus B virus have regions (epitopes) that are similar to cardiac protein myosin. After the virus is gone, the immune system may attack cardiac myosin. M protein is a virulence factor that can be produced by certain species of Streptococcus. M protein is strongly anti-phagocytic protein and is a major virulence factor. It binds to serum factor H, destroying C3 convertase and preventing opsonization by C3b. Cross-reactivity of anti-M protein antibodies with heart muscle is the basis for Rheumatic fever. Causes of Myocarditis Causes of Myocarditis: It develops secondary to an underlying infection caused by: 1-Commonly viruses, such as parvovirus B19. 2- Non-viral pathogens (less comm.only) such as : a- Bacterial infection: e.g. Borrelia burgdorferi (Lyme disease) b- Parasitic infection: e.g. Trypanosoma cruzi. c- Fungal infection: e.g. Asperigillus Viral Myocarditis Viral Myocarditis: Parvovirus B19: Erythrovirus B19: Erythroviruses belong to the Parvoviridae family of small DNA viruses. It is a nonenveloped, icosahedral virus that contains a single-stranded linear DNA genome. It is classified as erythrovirus because of its capability to invade red blood cell precursors in the bone marrow. Transmission: The virus is primarily spread by infected respiratory droplets; and blood- transfusion. Parvovirus B19 causes an infection in humans only. Electron micrograph of Parvoviruses in blood. Viral Myocarditis Role of Parvovirus B19 in disease: Fifth disease: - Fifth disease or erythema infectiosum is the fifth pink-red infectious rash described by physicians. - After being infected, patients usually develop the illness after an incubation period of four to fourteen days. - In adults, parvovirus B19 can lead to a autoimmune arthritis; due to formation of circulating virion-antibodies complexes. - Most patients have an arrest of erythropoiesis (production of red blood cells) during parvovirus infection (reticulocytopenia). - It is most dangerous in patients who have sickle cell anemia or hereditary spherocytosis. Viral Myocarditis Clinical picture of erythema infectiosum : Child showing signs of erythema infectiosum, also known as fifth disease. The "slapped cheek" appearance typical of fifth disease. Myocarditis Cellular infiltration and cardiac necrosis: Histopathological image of myocarditis at autopsy in a patient with acute onset of congestive heart failure due to viral infection. Viral Myocarditis Coxsackievirus group B and A: Coxsackievirus is a virus that belongs to a family of non-enveloped linear positivesense ssRNA viruses; Picornaviridae. -The genus Enterovirus, which includes poliovirus and echovirus, also belongs the Picornaviridae family. - Enteroviruses are transmitted by the fecal-oral route. Viral Myocarditis Group B and Group A Coxsackievirus: Group B, and to a lesser extent Group A Coxsackievirus are the main viral causes of acute myocarditis , and pericarditis. The virus invades the pharynx or gut wall to the lymphatics and then to the blood. Invasion of striated muscle, heart or pericardium takes place across small blood vessels and results in acute inflammation of the myofibrils causing chronic myocarditis, and dilated cardiomyopathy. Viral Myocarditis -Symptoms of infection with Coxsackieviruses group B include: fever, headache, sore throat, gastrointestinal disturbance , as well as chest and muscle pain. Other viral infections: • HIV, • Rubella virus, • Cytomegalovirus, and • Human herpesvirus 6 infections Could be complicated by myocarditis and pericarditis. Bacterial Myocarditis Bacterial Myocarditis: 1- Syphilis: Treponema pallidum infection: -Transmission: sexually, transplacental, vertical, blood transfusion. -Bacteriology: -Thin spirochete; Basically it has Gram’s negative cell envelope. -Axial filaments present (endoflagella). -Can not be cultivated in vitro; sero-diagnosis. - Pathogenesis: Tertiary syphilis: Anti-Cardiolipin antibodies in patient serum; Cardiovascular syphilis (myocarditis), aortic lesions, and Heart failure. :Cell mediated hypersensitivity. Bacterial Myocarditis 2- Lyme disease: Borrelia burgdorferi Borrelia burgdorferi is a species of Gram negative bacteria of the spirochete class of the genus Borrelia. Lyme disease is a zoonotic, vector-borne disease transmitted by ticks of the genus Ixodes from Rodent and Deer. The microbe is transmitted from lymph nodes, lymphatic vessels, and blood stream to cardiac muscle and CNS. Weeks to months after the onset, the second stage begins with myocarditis, cardiomyopathy, meningitis, and neuropathies. Bacterial Myocarditis Other Bacterial Myocarditis: Bacterial myocarditis is associated with immunodeficiency patients. Other bacteria that involved in bacterial Myocarditis are: Brucella, Corynebacterium diphtheriae, Gonococcus, Haemophilus influenzae, Actinomyces, Vibrio cholerae, Lleptospirosis, and Rickettsia. Fungal Infection Fungal infection: Aspergillosis : Aspergillosis develops mainly in individuals who are immunocompromised. The most common forms are allergic bronchopulmonary aspergillosis, pulmonary aspergilloma and invasive aspergillosis. Parasitic Myocarditis Parasitic Myocrditis: Trypanosoma cruzi: In Europe and North America, viruses are common cause of myocarditis. Worldwide, however, the most common cause is Chagas' disease, an illness endemic to Central and South America that is due to infection by the protozoan Trypanosoma cruzi. Transmission of trypanosomiasis occurs when the Winged bug of the genus Triatoma deposits feces on the skin surface and subsequently bites; the human host then contaminating the bite area, with infected feces. Parasitic Myocarditis Pathogenesis of Trypanosoma cruzi: Human American trypanosomiasis, or Chagas disease, is a fatal disease of humans. The parasite has two forms: 1. A trypomastigote found in human blood, and 2. An amastigote found in tissues. The acute form usually present as a localized swelling at the site of entry. In the chronic stage, 10 to 20 years after infection, the parasite invades the myofibrils of the heart causing myocarditis. The gradual autoimmune destruction of heart myocardium lead to cardiac enlargement and arrhythmias, and heart failure. Parasitic Myocarditis Parasitic Myocarditis Signs and Symptoms: The acute phase lasts for the first few weeks or months of infection. Mild symptoms can include fever, fatigue, body aches, headache, rash, loss of appetite, diarrhea, and vomiting. The signs on physical examination can include mild enlargement of the liver or spleen, swollen glands, and local swelling (a chagoma) where the parasite entered the body. The symptomatic chronic stage affects the nervous system, digestive system and heart. About two thirds of people with chronic symptoms have cardiac damage, including dilated cardiomyopathy, which causes heart rhythm abnormalities and may result in sudden death. Parasitic Myocarditis Cardiac muscle pathology; Chagas disease: Dilated cardiomyopathy and cardiac tissue damage due to Chagas disease. Cardiac tissue cross-section: parasite inside cardiac muscle. Blood film: Trypomastigotes Parasitic Myocarditis Toxoplasma gondii infection: Toxoplasma gondii is a species of parasitic protozoa in the genus Toxoplasma. The definitive host of T. gondii is the cat, but the parasite can be carried by many warm-blooded animals (birds or mammals, including humans). Toxoplasmosis, the disease of which T. gondii is the causative agent, is usually minor and self-limiting but can have serious or fatal effects on a fetus whose mother first contracts the disease during pregnancy or on an immunocompromised human. Parasitic Myocarditis Helminths causing Myocarditis: Ascaris, Echinococcus granulosus, schistosoma, Taenia solium, Trichinella spiralis, and Wuchereria bancrofti could be involved in Myocarditis. Trichinella spiralis is a nematode parasite, occurring in rats, pigs, bears and humans, and is responsible for the disease trichinosis. Humans typically become infected when they eat improperly cooked pork or Trichinella infected meat. Female Trichinella worms live for about six weeks, and in that time can produce up to 1,500 larvae. Larvae may migrate with blood to cardiac muscle causing myocarditis. Causes of Myocarditis Other causes of Myocarditis: Immunologic cause: 1- Rejection after a heart transplant. 2- Autoantigens: , systemic lupus erythematosis, sarcoidosis, and systemic vasculitis. 3- Toxins: (toxic shock syndrome toxin, carbon monoxide, snake venom, ethanol, and chemotherapy ). 4- Hypersensitivity response to some drugs. Purpura on the low limb due to medication induced vasculitis. Diagnosis of Myocarditis Diagnosis of Myocarditis: The most common test is a chest X-ray. Often the heart size is enlarged, the blood vessels of the lungs are prominent, and fluid may enter the lungs. Myocardial inflammation can be suspected on the basis of Electrocardiographic results (ECG) Elevated C-reactive protein (CRP) and/or Erythrocyte sedimentation rate (ESR) and increased IgM (serology) against viruses known to affect the myocardium. Markers of myocardial damage ( Troponin or creatine kinase cardiac isoenzymes) are elevated. A small tissue sample of the endocardium and myocardium is taken, and investigated by a pathologist by light microscopy and (if necessary) Immunochemistry and special staining methods. Diagnosis of Myocarditis Endo-myocardial biopsy specimen. Extensive eosinophilic infiltrate involving the endocardium and myocardium (hematoxylin and eosin stain).