Lecture 20: Infection See Flint et al, Appendix 2

General points: A general listing of different viral diseases that affect different organs of the body. Viruses infect specific Organisms Tissues Effects can range from Unnoticeable Deadly

Routes of viral entry The Metazoan body plan: We are essentially a tube.

Respiratory tract diseases Virus induced respiratory infections kill about 1 million children each year as well as a significant number of older adults. Many of the viruses that infect only the respiratory tract do not induce a strong immune response and hence reinfection with the same or a similar strain is common. Children get about 6 colds a year and adults get 2-3 per year. Deaths from respiratory infections: approx. 4.4 x 10 6 /yr for Bact. and viruses world wide. Influenza- 20,000 deaths/yr in US during epidemic years (most years), Spanish flu of 1918, 500,000 in US 20 x 10 6 worlwide, Hong Kong outbreak 68-69, 34,000 in US. Human Respiratory Syncytial Virus- 4,500 deaths/yr (children) in US.

Respiratory tract diseases Rhinitis (Common Cold)-watery nasal discharge and obstruction, sneezing, mild sore throat and coughing but little or no fever. Infection based in upper respiratory. Sometimes complicated by superinfection with bacteria. Rhinoviruses, coronaviruses Pharyngitis (most are viral)-sore throat, malaise, fever, sometimes cough. Infection based in pharynx. Can be caused by many of the same agents that cause common colds. RSV and adenovirus are prominent causes in young children and Herpes type viruses in young adults. Laryngotracheobronchitis (Croup)-fever, barking or metallic cough, respiratory distress, sometimes complete laryngeal obstruction. Most common causes are influenza and parainfluenza virus.

Respiratory tract diseases Bronchiolitis-Rapid and labored breathing, persistent cough, wheezing, cyanosis, variable amount of atelectasis, marked emphysema. Major causes are Influenza, parainfluenza, and RSV especially in young children. RSV can develop virtually overnight causing SIDS in young children. Pneumonia-often develops following upper resp. tract infection. Febrile, some cough, degree of dyspnea, wheezing, moist rales. X-rays often show only scattered areas of consolidation and diffuse lesions unlike pronounced lesions and consolidated areas in bacterial pneumonia. RSV, Influenza, parainfluenza, adenoviruses are major causes. A major cause of death to older people and young children. RSV is the major respiratory pathogen in young children and kills 4,500 children a year in the U.S. alone.

Viral Gastroenteritis Inflammation of the stomach and intestines Usually manifested as diarrhea which is watery but not bloody in the case of viral infection. Fever and Vomiting common with some infectious agents. Diarrheal diseases kill 3 million children each year mostly in developing countries. Rotaviruses are the main culprits and are responsible for most of the deaths. Astroviruses and Caliciviruses (Norwalk virus) can also cause diarrhea.

Central Nervous system diseases Most result as rare complication of primary infections elsewhere in the body. Viruses may be –neuroinvasive (able to enter the nervous system) and/or –neurovirulent (cause nerve damage). –e.g. Mumps is highly neuroinvasive but not very neurovirulent while herpes is just the opposite. Viruses cause disease in a variety of ways –infection of a specific area (Ammon's horn with rabies, and temporal lobes with HSV) –Broad infection. Some lyse neurons while some cause demyelination of axons.

Central Nervous system diseases Deaths - Measles which can cause a variety of brain infections kills about 1 million/yr worldwide, mostly in area without vaccination. Meningitis-Infection of meningeal cells. Viruses are major cause but viral infection is much less severe than bacterial with full recovery likely. Headache, Fever, and neck stiffness with/or without vomiting and photophobia are symptoms. Mumps and Enteroviruses are most common agents. Paralysis-Mostly from poliovirus in countries where the virus has not been eradicated. Poliomyelitis involving demyelination of nerve cells. Encephalitis-Fever, headache, neck stiffness, vomiting, alterations in state of consciousness indicating involvement of brain parenchymal tissue. Patient is lethargic and confused and seizures, or paralysis may develop before coma and death. Postinfectious Encephalitis- Occurs a few days after infection of children with measles, mumps, or varicella. Severe demyelination is observed and prognosis is grim.

Central Nervous system diseases Guillain-Barre syndrome- Demyelination is common finding. Most frequently caused by Epstein Barr Virus (EBV) infection and appearing 1-4 weeks after mononucleosis infection. Most recover completely but 15% have residual nerve damage. Reye's syndrome - Cerebral edema without inflammation is common symptom. 25% of cases are fatal. Follow influenza or chickenpox infection in children and seems to be an association between syndrome and aspirin administration. AIDS Dementia Complex - Results from destruction of nerve cells often late in AIDS syndrome (HIV). Direct destruction of nerve cells and demyelination are involved.

Skin Rashes Macular-Flat colored spots; Papular-Slightly raised containing no expressible fluid; Vesicles-blister with clear fluid from which virus can be isolated; Pustular- Blisters containing puss; Nodular- Generally warts.

Hemorrhagic fever A variety of diseases that share the common feature of widespread hemorrhages from the bodies epithelial tissue including internal mucosa such as the gastrointestinal tract and the skin. A variety of internal damage is often associated with the different diseases. Hanta virus for example causes severe renal necrosis. Other agents (Ebola and Yellow fever virus) cause severe liver damage. Many have high fatality rates.

Genitourinary infections Herpes simplex virus 2 and Papillomaviruses are the major viruses infecting the genital area. Sexual transmission is the main way of acquiring the agent. Herpes manifests as painful itchy ulcerated vesicular lesions occasionally accompanied by fever and malaise especially in woman. Spread to the central nervous system occurs in 10% of cases with mild meningitis resulting. Recurrences are common although generally less severe than the initial infection. Papillomaviruses: Genital warts. Warts appear as external condyloma and usually disappear without treatment within a couple of years. Certain types of HPV may progress over several years through stages of cervical intraepithelial neoplasia (CIN) to invasive squamous cell carcinoma. HIV: Deaths by HIV-about 1 million/yr worldwide, 20,000/yr in US although was much higher before triple drug therapy

Eye diseases A number of common childhood viral diseases can involve conjunctivitis –Inflammation of the conjunctiva which is the transparent membrane covering the sclera i.e. white of the eye and the inner eyelid). –Results in redness, discomfort and discharge and is commonly called pink eye. Some types are particularly dangerous, especially those involving the cornea (keratoconjunctivitis). Herpes Simplex Virus (HSV) is the commonest infectious agent that causes blindness in the Western world. A number of eye diseases, e.g. cataracts, glaucoma, and retinopathy are associated with congenital rubella syndrome and cytomegalic inclusion disease of infants.

Viral arthritis Stiff and painful joints. Usually accompanied by fever and myositis (inflammation of muscle tissue causing pain tenderness and weakness) Can occur with or without rash. Rarely persists for more than a few weeks. Major causative agents are certain toga-, flavi-, and bunyaviruses (arboviruses). It has been hypothesized that rheumatoid arthritis may have a viral origin.

Viral Carditis Myocarditis = inflammation of the heart muscle Pericarditis = inflammation of pericardium membrane that encloses he heart Cardiomyopathy = diseases causing reduction in the force of the heart Associated with certain enteroviruses (family of picornaviruses), most notably coxsackie B virus. Infections often reoccur, leading to permanent myocardial damage, cardiomegaly (enlarged heart), or congestive cardiac failure.

Viral Hepatitis Inflammation of the liver with accompanying liver cell damage cases per 100,000 people per year in the U.S. Symptoms :jaundice often proceeded by flu-like illness. Liver failure can occurs. Can become chronic depending on the infectious agent and cirrhosis Transmission: –parenteral (needle infection usually), –perinatal (occurring just before or after birth), –sexual, or enteric (via gut cells). 5 viruses known to infect the liver as the primary organ. Other viruses can also cause hepatitis e.g. Herpes viruses and some viruses causing hemorrhagic fever. Deaths- Hepatitis B is the most common killer killing 2 million/yr worldwide and 5000/yr in US.

Viral pancreatitis and diabetes Mumps infection can be complicated by severe pancreatitis (inflammation of the pancreas). Can also be caused by certain other enteroviruses. There is some evidence that viral infections triggers insulin-dependent juvenile diabetes mellitus.

Chronic fatigue syndrome Characterized by extreme fatigue. EBV, Coxsackie B, CMV, and HTLV are among the many viruses to be isolated from such patients Importantly, no cause-effect relationship has been established

Congenital and Perinatal Infections Include a variety of diseases acquired –Prenatally, –Intrapartum (during birth process) or –Postnatally within the first few weeks. Can be particularly dangerous since the newborn is not protected by the mothers antibodies