Viral Diseases

Victor Politi, MD,FACP Medical Director, SVCMC School of Allied Health Professions, Physician Assistant Program

Introduction

• In 1898, Friedrich Loeffler and Paul Frosch found evidence that the cause of foot-and-mouth disease in livestock was an infectious particle smaller than any bacteria. Friedrich Loeffler • This was the first clue to the nature of viruses, genetic entities that lie somewhere in the grey area between living and non-living states.

Introduction

• Viruses depend on the host cells that they infect to reproduce. • When found outside of host cells, viruses exist as a protein coat or

capsid

, sometimes enclosed within a membrane. • The capsid encloses either DNA or RNA which codes for the virus elements.

Introduction

• When it comes into contact with a host cell, a virus can insert its genetic material into its host, literally taking over the host's functions. • An infected cell produces more viral protein and genetic material instead of its usual products.

Introduction

• Some viruses may remain dormant inside host cells for long periods, causing no obvious change in their host cells (a stage known as the

lysogenic

phase)

Lysogenic cycle

In the lysogenic cycle, the virus reproduces by first injecting its genetic material, indicated by the red line, into the host cell's genetic instructions.

Lytic Phase

• But when a dormant virus is stimulated, it enters the

lytic

phase: new viruses are formed, self-assemble, and burst out of the host cell, killing the cell and going on to infect other cells.

Lytic phase/cycle

In the lytic cycle, The virus reproduces itself using the host cell's chemical machinery. The red spiral lines in the drawing indicate the virus's genetic material. The orange portion is the outer shell that protects it.

Transduction

• Viruses also carry out natural "genetic engineering": a virus may incorporate some genetic material from its host as it is replicating, and transfer this genetic information to a new host, even to a host unrelated to the previous host. • This is known as

transduction

, and in some cases it may serve as a means of evolutionary change - although it is not clear how important an evolutionary mechanism transduction actually is.

• Viruses cause a number of diseases in eukaryotes. • In humans, smallpox, the common cold, chickenpox, influenza, shingles, herpes, polio, rabies, Ebola, hanta fever, and AIDS are examples of viral diseases. • Even some types of cancer -- though definitely not all -- have been linked to viruses.

• Virus particles are about one-millionth of an inch (17 to 300 nanometers) long. • Viruses are about a thousand times smaller than bacteria, and bacteria are much smaller than most human cells. • Viruses are so small that most cannot be seen with a light microscope, but must be observed with an electron microscope.

Relative size of viruses and bacteria

Relative size of DNA viruses

Relative size of positive strand RNA viruses

Relative size of negative strand RNA viruses

• The internationally agreed system of virus classification is based on the structure/composition of the virus particle (virion) • In some cases, the mode of replication is also important in classification. • Viruses are classified into various families on this basis.

• A virus particle, or

virion

, consists of the following: –

Nucleic acid

- either DNA or RNA, either single stranded or double-stranded –

Coat of protein

- Surrounds the DNA or RNA to protect it –

Lipid membrane

- Surrounds the protein coat (found only in some viruses, including influenza; these types of viruses are called

enveloped

viruses as opposed to

naked

viruses)

• Viruses can exist for a long time outside the body. • The way that viruses spread is specific to the type of virus. They can be spread through the following means: –

Carrier organisms

– mosquitoes,ticks, fleas – –

The air Direct transfer of body fluids

from one person to another - saliva, sweat, nasal mucus, blood, semen, vaginal secretions –

Surfaces on which body fluids have dried

Papillomaviruses

• Papilloma viruses are wart-causing viruses that cause human neoplasms • Warts are usually benign but can convert to malignant carcinomas. • This occurs in patients with epidermodysplasia verruciformis. • Papilloma viruses are also found associated with human penile, uterine and cervical carcinomas and are very likely to be their cause.

Epidermodysplasia verruciformis

• This widespread, markedly pruritic, erythematous eruption was eventually found to be caused by human papillomavirus infection.

Papillomaviruses

• There are 51 types of papilloma viruses • Not all are associated with cancers; however, papillomas may cause 16% of female cancers worldwide and 10% of all cancers.

Papilloma virus

Papillomaviruses

• Vulvar, penile and cervical cancers are associated with type 16 and type 18 papilloma viruses. • The most common genital human papilloma viruses (HPV) are types 6 and 11.

Human polyoma viruses

• This virus causes progressive multifocal leukoencephalopathy ,a disease associated with immunosuppression. • In 1979, the rate of occurrence of this disease was 1.5 per 10 million population. • It has become much more common because of AIDS and is seen in 5% of AIDS patients.

Herpes Viruses

• Herpes viruses are a leading cause of human viral disease, second only to influenza and cold viruses. • They are capable of causing overt disease or remaining silent for many years only to be reactivated, for example as shingles.

Herpes Viruses

• The name herpes comes from the Latin

herpes

which, in turn, comes from the Greek word

herpein

which means to creep. • This reflects the creeping or spreading nature of the skin lesions caused by many herpes virus types.

Human Herpes viruses

• Herpes simplex virus (HSV) type 1 • HSV type 2 • Varicella zoster virus (type 3) • Epstein-barr (EB) infectious mononucleosis virus (type 4) • Cytomegalovirus –CMV type 5 • HHV-6 (causative agent of roseola) • HHV-7 • HHV-8- linked with Kaposi sarcoma

Human Herpes viruses

• Once a patient has become infected by herpes virus, the infection remains for life. • The initial infection may be followed by latency with subsequent reactivation.

Human Herpes viruses

• Herpes viruses infect most of the human population and persons living past middle age usually have antibodies to most of the above herpes viruses with the exception of HHV-8.

Herpes viruses 1 & 2

• Herpes simplex 1 and 2 are frequently benign but can also cause severe disease. • In each case, the initial lesion looks the same. – A clear vesicle containing infectious virus with a base of red (erythomatous) lesion at the base of the vesicle. – This if often referred to as a 'dewdrop on a rose petal'. – From this pus-containing (pustular), encrusted lesions and ulcers may develop.

Herpes viruses 1 & 2

• Affect primarily the oral and genital areas • Disease is typically a manifestation of reactivation – Triggers for clinical reactivation are not well understood

Herpes Viruses 1&2

• Herpes simplex type 1 (HSV-1) – Largely involves mouth/oral cavity (herpes labialis) – Can cause urogenital infections • HSV-2 – Most common cause of genital ulcers in developing world

HSV-1

• Primary infection may be asymptomatic • Vesicles form moist ulcers after several days – if untreated epithelialize over 1-2 weeks • Recurrences – Tend to be labial – Heal faster – Induced by stress, fever, infection, sunlight

HSV-2

• Genital herpes is usually the result of HSV-2 with about 10% of cases being the result of HSV-1. • Primary infection is often asymptomatic but many painful lesions can develop on the glans or shaft of the penis in men and on the vulva, vagina, cervix and perianal region of women Largely involve genital tract

Hsv-2

• Typical lesions – Multiple, painful, small, grouped and vesicular

HSV- Diagnosis

• Usually made on clinical grounds • Viral cultures of vesicular fluid • Direct fluorescent antibody staining of scraped lesions • In serum – can be identified using PCR • Cells may be obtained from the base of the lesion (called a Tzank smear) and histochemistry performed • presence of intranuclear inclusions and multinucleated giant cells supportive of dx of herpes

HSV-Clinical Findings

• Ocular dx (keratitis, blepharitis, keratoconjunctivitis) • Neonatal & congenital infection • Encephalitis/recurrent meningitis • Disseminated infection • Bell’s Palsy • Esophagitis • Erythema Multiforme

Herpes keratitis

• This is an infection of the eye and is primarily caused by HSV-1. • It can be recurrent and may lead to blindness. • It is a leading cause of corneal blindness in the United States.

Herpes whitlow

This disease of persons who come in manual contact with herpes-infected body secretions can be cause by either type of HSV and enters the body via small wounds on the hands or wrists. It can also be caused by transfer of HSV-2 from genitals to the hands

HSV encephalitis

• This is usually the result of an HSV-1 infection and is the most common sporadic viral encephalitis. • HSV encephalitis is a febrile disease and may result in damage to one of the temporal lobes. • As a result there is blood in the spinal fluid and the patient experiences neurological symptoms such as seizures. • The disease can be fatal but in the US there are fewer than 1000 cases per year.

HSV- Treatment/Prevention

• Urogenital, encephalitic or disseminated disease – acyclovir & related compounds • Keratitis – trifluridine • Resistant strains in immunocompromised – foscarnet

Prevention

• Recurrent mucocutaneous disease is most effectively treated with acyclovir • Recurrent genital disease also requires barrier precautions during sexual activity • Asymptomatic transmission occurs – especially with HSV-2

Varicella & Herpes Zoster Chicken pox or shingles (its reactivation) •

Chicken Pox

– Highly contagious – Generally dx of childhood – Spread by inhalation of infected droplets or contact with lesions after 10-20 days – Fever/malaise mild in children – Pruritic rash evolves centrifugally – beginning on face/scalp/trunk – lesser degree on extremities •

Shingles

– After primary infection virus remains dormant in nervous tissue – Pain often severe, may precede rash – Lesions follow any nerve root distribution – typically thoracic & lumbar – Ramsay Hunt Syndrome – geniculate ganglion involvement

• Typical isolated rash in shingles • In severe cases of shingles, the lesions coalesce, forming a disfiguring carpet of scabs and sometimes the rash leaves permanent scars

Varicella & Herpes Zoster Chicken pox or shingles (its reactivation) • Varicella Complications – – Interstitial pneumonia • more common in adults than children – Hepatitis – Reye’s syndrome • Usually in childhood/associated with aspirin use – Congenital malformation • congenital varicella syndrome which leads to scarring of the skin of the limbs, damage to the lens, retina and brain and microphthalmia – Secondary bacterial infection • Group A beta-hemolytic streptococci common

Varicella & Herpes Zoster Chicken pox or shingles (its reactivation) • Herpes Zoster – Postherpetic neuralgia • Occurs in 60-70% of patients > age 60 – Encephalitis, skin lesions beyond the dermatome, and visceral lesions • Seen in immunocompromised & HIV patients

Epstein- Barr Virus

Epstein-Barr virus is the causative agent of Burkitt's lymphoma in Africa, nasal pharyngeal carcinoma in the orient and infectious mononucleosis in the west.

EBV

• Why this virus causes a benign disease in some populations but malignant disease in others is unknown. Burkitt's Lymphoma caused by Epstein-Barr Virus

Infectious mononucleosis

• The primary infection is often asymptomatic.

• Some patients develop infectious mononucleosis after 1 2 months of infection. • The disease is characterized by malaise, lymphadenopathy, tonsillitis, enlarged spleen and liver and fever. • The fever may persist for more than a week. • There may also be a rash. • The severity of disease often depends on age (with younger patients resolving the disease more quickly) and resolution usually occurs in 1 to 4 weeks.

Infectious mononucleosis

Complications

• Complications include: – neurological disorders such as meningitis, encephalitis, myelitis and Guillain Barrè syndrome – Secondary infections, – autoimmune hemolytic anemia, – thrombocytopenia – agranulocytosis, – aplastic anemia

Infectious mononucleosis

• A large proportion of the population (90 95%) is infected with Epstein-Barr virus and these people, although usually asymptomatic, will shed the virus from time to time throughout life. • The virus is spread by close contact (kissing disease).

Infectious mononucleosis

• Up to 80% of students entering college in the US are seropositive for the virus and many of those that are negative will become positive while at college. • The virus can also be spread by blood transfusion.

• Tongue and palate of patient with infectious mononucleosis.

Infectious mononucleosis Dx

• In infectious mononucleosis, blood smears show the atypical lymphocytes (Downey cells). • There are also serological tests available. • Heterophile antibodies are produced by the proliferating B cells and these include an IgM that interacts with Paul-Bunnell antigen on sheep red blood cells.

Infectious mononucleosis- Tx

• Unlike herpes simplex virus, there are no drugs available to treat Epstein-Barr virus.

• A vaccine is being developed.

Major Vaccine –Preventable Viral Infections

• Measles • Mumps • Poliomyelitis • Rubella

Measles

• Before the advent of the current measles vaccine, there were about 500,000 cases of measles in the United States per year; almost everyone got the measles. • Infection is via an aerosol route and the virus is very contagious.

Measles

• Uncomplicated disease is characterized by the following: – Fever of 101 degrees Fahrenheit or above – Respiratory tract symptoms: running nose (coryza) and cough – Conjunctivitis – Koplik's spots on mucosal membranes - small (1 3mm), irregular, bright red spots, with bluish-white speck at center. The patient may get an enormous number and red areas may become confluent – Maculopapular rash which extends from face to the extremities.

Measles

• Koplik’s spots on palate due to pre eruptive measles on day 3 of the illness

Measles

• classic day-4 rash with measles.

Measles Complications

• CNS – Encephalitis – Subacute sclerosing panencephalitis – Subacute measles encephalitis • Respiratory Tract – Bronchopneumonia – bronchiolitis • Secondary bacterial infection • Gastroenteritis

Measles Prevention/Tx

• Prevention – Vaccination • Treatment – Isolation one week following onset of rash – Symptomatic – Vitamin A 200,000 units/d orally reduces pediatric morbidity rates (maintenance of GI and respiratory epithelial mucosa, immune enhancement)

Mumps

• Mumps is usually defined as acute unilateral or bilateral parotid gland swelling that lasts for more than two days with no other apparent cause. • Mumps is very contagious and is probably usually acquired from respiratory secretions and saliva via aerosols or fomites.

Mumps

• The virus is secreted in urine and so urine is a possible source of infection. • It is found equally in males and females.

Mumps

• Before 1967, most mumps patients were under 10 years of age but since the advent of the attenuated vaccine, the remaining cases occur in older people with almost half being 15 years of age or older.

Mumps

•

Inflammation, parotitis, in a child with mumps.

• Virus is shed in saliva from 3 days before to 6 days after symptoms

Pathogenesis of mumps

• Virus infects upper/lower respiratory tract leading to local replication. • The virus spreads to lymphoid tissue which, in turn, leads to viremia. • The virus thus spreads to a variety of sites, including salivary, other glands and other body sites (including the meninges).

Pathogenesis of mumps

Symptoms of Mumps

• Parotitis • Fever and malaise • Deafness – was a leading cause of acquired deafness before the advent of mumps vaccines but hearing loss is rare (one in every 20,000 mumps cases). • Orchioitis – especially severe in adolescent and adult males and occurs in about 50% of cases

Mumps Complications

• Meningitis • Pancreatitis – Leading cause in children • Oophoritis • Thyroiditis • Neuritis • Hepatitis • Myocarditis • Thrombocytopenia • Migratory arthralgias • nephritis

Mumps Prevention/Tx

• Prevention – Vaccination • Treatment – Symptomatic – Isolation

Rubella

• Rubella (which means "little red" and is also known as German measles) was originally though to be a variant of measles. • It is a mild disease in children and adults, but can cause devastating problems if it infects the fetus, especially if infection is in the first few weeks of pregnancy.

Rubella

• Rubella virus is spread via an aerosol route and occurs throughout the world.

• The initial site of infection is the upper respiratory tract. • The virus replicates locally (in the epithelium, lymph nodes) leading to viremia and spread to other tissues. • As a result the disease symptoms develop.

Rubella

• Rash (if it occurs) starts after an incubation period of approximately 2 weeks (12 to 23 days) from the initial infection. • There is usually no prodrome in young children but in older children and adults disease results in low grade fever, rash, sore throat and lymphadenopathy.

Rubella

• Complications are extremely rarely (1 in 6000 cases). – Rubella encephalopathy may occur about 6 days after rash. It usually lasts only a few days and most patients recover (no sequelae). If death occurs, it is within few days of onset of symptoms.

• Other rare complications include orchitis, neuritis and panencephalitis.

Rubella

• The risk to a fetus is highest in the first few weeks of pregnancy and then declines in terms of both frequency and severity.

Rubella

• Congenital rubella with hemorrhagic lesions in the skin.

Rubella

• The sequelae of congenital rubella syndrome are: – Hearing loss. This is the most common sequella of congenital rubella infection especially when the latter occurs after four months of pregnancy.

– Congenital heart defects – Neurologic problems (psychomotor retardation, mental retardation, microcephaly) – Ophthalmic problems intrauterine growth retardation – Thrombocytopenia purpura – Hepatomegaly – Splenomegaly

Rubella

• Baby born with rubella: – Thickening of the lens of the eye that causes blindness (cataracts)

•

Rubella Treatment/Prevention

• Treatment – There is no specific treatment. – Supportive care should be used • Vaccination – Childhood Immunization – It is important that women are vaccinated prior to their first pregnancy.

ENTEROVIRUSES

• Enteroviruses are spread via the fecal-oral route. • The ingested viruses infect cells of the oro-pharyngeal mucosa and lymphoid tissue (tonsils) where they are replicated and shed into the alimentary tract. • From here they may pass further down the gastrointestinal tract.

ENTEROVIRUSES

• Most patients infected with an enterovirus remain asymptomatic but in small children benign fevers caused by unidentified enteroviruses are relatively common (non specific febrile illness). • Many outbreaks of febrile illness accompanied by rashes are also caused by enteroviruses

Poliovirus

• Poliovirus caused about 21, 000 cases of paralytic poliomyelitis in the United States each year in the 1940's - 50's prior to the introduction of the Salk (inactivated) and Sabin (attenuated) vaccines.

• Infection by polio virus is, in most cases, asymptomatic.

Abortive poliomyelitis (minor illness)

• The first symptomatic result of polio infection is febrile disease and occurs in the first week of infection. • The patient may exhibit a general malaise which may be accompanied by vomiting, a headache and sore throat. • This is abortive poliomyelitis and occurs in about 5% of infected individuals

Non-paralytic poliomyelitis

• Three or four days later a stiff neck and vomiting, as a result of muscle spasms, may occur in about 2% of patients. • This is similar to aseptic meningitis. The virus has now progressed to the brain and infected the meninges.

Paralytic polio

• About 4 days after the end of the first minor symptoms, the virus has spread from the blood to the anterior horn cells of the spinal cord and to the motor cortex of the brain. • The degree of paralysis depends on the which neurons are affected and the amount of damage that they sustain. • The disease is more pronounced in very young and very old patients.

Paralytic polio

• In spinal paralysis one or more limbs may be affected or complete flaccid paralysis may occur • .

Paralytic polio

• In bulbar paralysis cranial nerves and the respiratory center in the medulla are affected leading to paralysis of neck and respiratory muscles. • There is no sensory loss associated with the paralysis.

Paralytic polio

• The degree of paralysis may increase over a period of a few days and may remain for life or there may be complete recovery over period of 6 months to a few years

Paralytic polio

• In bulbar poliomyelitis, death may also ensue in about three quarters of patients, especially when the respiratory center is involved. • Patients were able to survive for a while using an iron lung to aid respiration.

• The morality rate of paralytic polio is 2-3%

Post-polio syndrome

• This afflicts victims of an earlier polio virus infection but the virus is no longer present. • It may occur many years after the infection and involves further loss of function in affected muscles perhaps as a result of further neuron loss.

COXSACKIE VIRUSES

• There are many infections caused by Coxsackie viruses, most of which are never diagnosed precisely.

COXSACKIE VIRUSES

• Coxsackie type A – usually is associated with surface rashes (exanthems) while • Coxsackie type B – typically causes internal symptoms (pleurodynia, myocarditis) • but both can also cause paralytic disease or mild respiratory tract infection.

COXSACKIE VIRUSES

• Enteroviruses are the major cause of viral meningitis. • Both Coxsackie virus A and B can cause aseptic meningitis which is so-called because it is not of bacterial origin.

COXSACKIE VIRUSES

• Viral meningitis typically involves a headache, stiff neck, fever and general malaise. • Lymphocyte pleocytosis of the cerebrospinal fluid is often observed. • Most patients recover from the disease unless encephalitis occurs although there may be mild neurological problems. • The disease is most prevalent in the summer and fall.

COXSACKIE VIRUSES Herpangina

• Coxsackie virus A can cause a fever with painful ulcers on the palate and tongue leading to problems swallowing and vomiting. • Treatment of the symptoms is all that is required as the disease subsides in a few days. • Despite its name, the disease has nothing to do with herpes or the chest pain known as angina.

COXSACKIE VIRUSES Hand, foot and mouth disease

• This is an exanthem caused by Coxsackie type A16. • Symptoms include fever and blisters on the hands, palate and feet. • It subsides in a few days. • Many other exanthems may be caused by Coxsackie virus or Echoviruses.

COXSACKIE VIRUSES Hand, foot and mouth disease

COXSACKIE VIRUSES Hand, foot and mouth disease

• Coxsackie virus A and B (and also Echoviruses) can cause myocarditis in neonates and young children. • Fever, chest pains, arrhythmia and even cardiac failure can result. • Mortality rates are high. • In young adults, an acute benign pericarditis may also be cause by Coxsackie viruses

COXSACKIE VIRUSES Bornholm disease (Pleurodynia, the Devil's Grippe)

• • •

Usually caused by Coxsackie A, these upper respiratory tract infections can result in fever and sudden sharp pains in the intercostal muscles on one side of the chest. There may also be pain in the abdomen and vomiting. The incubation period is 2 to 4 days and symptoms subside after a few days although relapses can occur.

Other enterovirus diseases

• Non-specific febrile disease can be caused by several enteroviruses.

• These infections are among the most common reasons that small children are admitted to hospital in order to rule out a bacterial cause.

Other enterovirus diseases

• Admissions peak in the late summer/fall. • Disease normally resolves but can be of consequence in the very young. • Coxsackie B virus may result in severe neonatal disease including hepatitis, meningitis, myocarditis and adreno-cortical problems.

Other enterovirus diseases

• Infections often spread through nurseries and are difficult to stop because of the resistance of the virus to disinfecting agents.

PARAINFLUENZA, RESPIRATORY SYNCYTIAL AND ADENO VIRUSES

PARAINFLUENZA VIRUS

• Parainfluenza viruses are viral pathogens causing upper and lower respiratory infections in adults and children.

• Parainfluenza viruses -relatively large viruses of about 150-300 nm in diameter.

PARAINFLUENZA VIRUS

• Infections occur as epidemics as well as sporadically.

• Parainfluenza viruses are sensitive to detergents and heat but can remain viable on surfaces for up to 10 hours.

• Transmission occurs via the following routes: – Large droplets - person to person through close contact – Aerosols of respiratory secretions – Fomites (virus survives on surfaces)

PARAINFLUENZA VIRUS

• Incubation period is 2 to 6 days.

• Most infections are asymptomatic, especially in older children and adults.

• Primary infections and re-infections occur.

• Most persons have had primary infections before the age of 5 yrs.

PARAINFLUENZA VIRUS

• Reinfections are clinically less severe, most commonly involve the upper respiratory tract and occur throughout life.

• Fever and a spectrum of respiratory infections are caused by PIVs – Rhinorrhea/rhinitis, pharyngitis, cough, croup (laryngotracheobronchitis), bronchiolitis, and pneumonia

PARAINFLUENZA VIRUS Antigen detection

• Radio-immunoasay, enzyme immunoassay, fluoro-immunoassay, and immunofluoresence methods are used for antigen detection.

• Nasopharyngeal secretions are collected, from swabs or washings and transported in viral transport medium and on ice.

• Shell vial assay is useful in detecting growth in 4-7 days. Hemadsorption can be noted before cytopathic effects. Immunofluoresence is confirmatory.

PARAINFLUENZA VIRUS

• There is no specific treatment. • Supportive treatment for croup includes humidification of air and racemic epinephrine. • Corticosteroids may be used in moderate to severe cases.

PARAINFLUENZA VIRUS

• Immunity following infection is short lived. • The role of antibody is not clear since reinfection has been seen even with high levels of antibody.

• Cell-mediated Immunity (CMI) is probably more important for limiting infection.

RESPIRATORY SYNCYTIAL VIRUS

• These viruses survive on surfaces for up to 6 hours, on gloves for less than 2 hours. • They rapidly lose viability with freeze-thaw cycles, in acidic conditions and with disinfectants.

RSV

• RSV has a worldwide distribution and most children have had an RSV infection by age 4 years • Out breaks are seasonal occurring from late fall through spring (November to May) • The virus is transmitted via large droplets, through fomites and via hands

RSV -Epidemiology

• The virus enters through the eyes and nose • Viral shedding continues for less than 1 to 3 weeks but longer in immuno compromised hosts • RSV is the most frequent cause of bronchiolitis but is an infrequent cause of croup

RSV-Clinical Features

• Incubation Period: 4 - 6 days (range: 2 - 8 days) • Upper respiratory infection (‘bad cold’) in older children and adults: • Clinical features: fever, rhinitis, pharyngitis

RSV- Clinical Features

• Lower respiratory infection- Bronchiolitis and/or pneumonia may occur after the upper respiratory infection: • Clinical features: cough, tachypnea, respiratory distress, hypoxemia, cyanosis.

• Cough can persist for 3 weeks.

RSV- Clinical Features

• In young infants - apnea, lethargy, irritability, poor feeding.

• Radiological features: atelectasis, streaking, hyperinflation.

• Severe infections occur in pre-term infants (especially less than 35 weeks gestation and those with chronic lung disease), children with cyanotic congenital heart disease, and immuno-compromised hosts.

RSV-Dx/Tx

• Nasal washings, nasal aspirates or swabs • Treatment is usually supportive – – fluids, oxygen, humidification of air, respiratory support, bronchodilators

ADENOVIRUS

• Almost half of adenoviral infections are subclinical • Most infections are self-limited and induce type-specific immunity • Incubation period is 2-14 days; for gastroenteritis usually 3-10 days

Adenovirus Symptoms

• Eye – Epidemic Keratoconjunctivitis (EKC), acute follicular conjunctivitis, pharyngoconjunctival fever • Respiratory system – rhinitis, pharyngitis (with or without fever), tonsillitis, bronchitis, pharyngoconjunctival fever, acute respiratory disease (LRI), pertussis-like syndrome, pneumonia sometimes with sequelae

Adenovirus Symptoms

• Genitourinary – Acute hemorrhagic cystitis, orchitis, nephritis, oculogenital syndrome • Gastrointestinal – Gastroenteritis, mesenteric adenitis, intussusception, hepatitis, appendicitis. Diarrhea tends to last longer than with other viral gastroenteritides

Adenovirus Complications

• Rare results of adenovirus infections include – Meningitis, encephalitis, arthritis, skin rash, myocarditis, pericarditis, hepatitis. – Fatal disease may occur in immunocompromised patients, as a result of a new infection or reactivation of latent virus

Adenovirus - Epidemiology

• Endemic, epidemic and sporadic infections occur. • Outbreaks have been noted in military recruits, swimming pool users, residential institutions, hospitals, day care centers etc.

• Transmission: Droplets, fecal-oral route (direct and through poorly chlorinated water), fomites

Adenovirus - Epidemiology

• Infections are most communicable in the first few days of illness, however infective period continues since clinical infection may be followed by intermittent and prolonged rectal shedding • Secondary attack rate within families: up to 50%;

Adenovirus

• Adenovrius outbreaks: – Respiratory disease mainly occurs in late winter through early summer. – Pharyngoconjunctival and EKC infections occur in the summer months – However GI disease does not seem to be seasonal

Influenza

• True influenza is an acute infectious disease caused by a member of the orthomyxovirus family • The term 'flu' is often used for any febrile respiratory illness with systemic symptoms that may be caused be a myriad of bacterial or viral agents as well as influenza.

Influenza

• Influenza outbreaks usually occur in the winter in temperate climates. • In the United States, the 'flu season usually starts in October or November and is at its height from December to March

Influenza

• Major outbreaks of influenza are associated with influenza virus type A or B. • Infection with type B influenza is usually milder than type A. • Type C virus is associated with minor symptoms.

Influenza

• The virus is spread person to person via small particle aerosols (less than 10µm) which can get into respiratory tract. • The incubation period is short, about 18 to 72 hours.

Influenza

• Virus concentration in nasal and tracheal secretions remains high for 24 to 48 hours after symptoms start and may last longer in children. • Titers are usually high and so there are enough infectious particles in a small droplet to start a new infection.

Influenza

• Influenza virus infects the epithelial cells of the respiratory tract. • The disease is usually most severe in very young children and the elderly.

Influenza & Children

• Children may have no antibodies and the small diameter of components of the respiratory tract in the very young mean that inflammation and swelling can lead to blockage of parts of respiratory tract, sinus system or Eustachian tubes.

Influenza & the Elderly

• In the elderly, influenza is often severe because they often have an underlying decreased effectiveness of the immune system and/or chronic obstructive pulmonary disease or chronic cardiac disease.

Influenza – Statistics

• CDC surveys show that each year about 114,000 people in the U.S. are hospitalized and about 36,000 people die because of the flu.

Influenza – Statistics

• Flu and pneumonia together constitute the sixth leading cause of deaths in the United States. – Most flu fatalities are 65 years and older. – Children younger than 2 years old are as likely as those over 65 to have to be hospitalized because of the flu.

Influenza -Symptoms

• Uncomplicated influenza – Fever – Myalgias, headache – Ocular symptoms - photophobia, tears, ache – Dry cough, nasal discharge

Influenza - Complications

• Pulmonary complications: – Croup in young children - symptoms include cough (like a barking seal), difficulty breathing, stridor (crowing sound in inspiration) – Primary influenza virus pneumonia – Secondary bacterial infection: • Often involves

Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae

Influenza - Complications

• Complications often occur in patients with underlying chronic obstructive pulmonary or heart disease. • The underlying problems may not have been recognized prior to the influenza infection.

Influenza - complications

• Non-pulmonary complications: – Myositis (rare, more likely to be seen in children after type B infection) – Cardiac complications – Encephalopathy – Reye’s Syndrome – Guillain Barre Syndrome

Influenza - Complications

• The major causes of influenza-associated death are bacterial pneumonia and cardiac failure. Ninety per cent of deaths are in people over 65 years of age.

Influenza - Dx

• Firm diagnosis is by means of virus isolation and serology. The virus can be isolated from the nose or a throat swab.

Influenza Prevention

• A new vaccine is formulated annually with the types and strains of influenza predicted to be the major problems for that year (predictions are based on worldwide monitoring of influenza). • The vaccine is multivalent and the current one is to two strains of influenza A and one of influenza B.

Influenza - Tx

• The best treatments are rest, liquids, anti febrile agents (not aspirin in the young or adolescent, since Reye's disease is a potential problem). • Be aware of and treat complications appropriately.

ROTAVIRUSES

• Rotavirus is stable in the environment and is relatively resistant to handwashing agents. • Is susceptible to disinfection with 95% ethanol, ‘Lysol’, formalin and in environments with pH<2.

ROTAVIRUSES

•

Distribution

– – Worldwide, causing 600,000-850,000 deaths per year (figure 3).

• Seroprevalence studies show that antibody is present in most infants by age 3 years.

• In the U.S., there are 20 - 40 deaths per year with 50,000 hospitalizations per year • Dehydration=1-2.5%

ROTAVIRUSES

• In the U.S.A., rotavirus infections occur in the winter months (November through May). • •

Incubation period

- thought to be <4 days

Contagious Period

- Before onset of diarrhea to a few days after end of diarrhea

ROTAVIRUSES

•

Age

- Rotaviruses infect children at a young age. • Older infants and young children (4 months - 2 years) tend to be more symptomatic with diarrhea. • Young infants may be protected due to trans-placental transfer of antibody.

ROTAVIRUSES

• Asymptomatic infections are common, especially in adults. Many cases and outbreaks are nosocomial • Group A infections are most common.

• Group B has been associated with outbreaks in adults in China • Group C is responsible for sporadic cases of diarrhea in infants around the world.

ROTAVIRUSES

• Spread is mainly person to person via fecal - oral route and through fomites. • Spread by food and water is also possible. Spread via respiratory route is speculated.

• High numbers of viral particles are shed in diarrheal stools.

ROTAVIRUSES

• Fever- can be high grade (>102° F in 30% of patients) • Vomiting, nausea precedes diarrhea.

• Diarrhea is usually watery (no blood or leukocytes), lasting 3-9 days, but longer in malnourished and immune deficient individuals. Necrotizing entercocolitis and hemorrhagic gastroenteritis is seen in neonates

ROTAVIRUSES

• •

Dehydration is the main contributor to mortality.

Secondary malabsorption of lactose and fat, and chronic diarrhea are possible

ROTAVIRUSES- DX

• Rapid diagnosis - antigen detection in stool by ELISA (uses a monoclonal antibody) and LA

ROTAVIRUSES- Tx

• Supportive - rehydration (oral / intravenous) • Antiviral agents not known to be effective

NORWALK VIRUS AND NORWALK-LIKE VIRAL AGENTS

• First detected in stools of patients with gastroenteritis in Norwalk, Ohio in 1972.

NORWALK VIRUS AND NORWALK-LIKE VIRAL AGENTS

• Adults and children are affected • Relatively short incubation period: <24 hours • Illness is short (<3 days) • Nausea, vomiting, abdominal cramping and watery diarrhea accompanied by headache, fever and malaise • Outbreaks often occur in institutions, cruise ships, etc. through contaminated food or water • Feco-oral spread, perhaps also spread through vomitus

Rhinoviruses

• Rhinoviruses are one of the families of viruses that can cause the common cold although many other viruses can infect the respiratory tract and cause cold-like symptoms. • It is estimated that about one third of "colds" are caused by rhinovirus infections.

Rhinoviruses

• Spread by aerosols - can also be spread by fomites such as hands and other forms of direct contact. • Rhinoviruses are quite stable, lasting for hours on fomites, but are sensitive to temperature.

Rhinoviruses

• The symptoms of a rhinovirus infection are well known: discharging or blocked nasal passages often accompanied by sneezes, and perhaps a sore throat. • Rhinorhea may be accompanied by a general malaise, cough, sore throat etc. • The characteristic symptoms occur from one to four days after infection

Rhinoviruses

• Rhinovirus infections usually occur at times of increased human contact, that is in the colder months of the year. • Many different serotypes circulate simultaneously. • Frequently children become infected and then pass the virus to adults after an incubation time of about two or three days. • Often as many as one half of the contacts get a cold in this way.

Rhinoviruses

• Many infections by other viruses cause symptoms that are similar to those of rhinoviruses. These include parainfluenzaviruses, coronaviruses and enteroviruses

HEPATITIS VIRUSES

• Several diseases of the liver, collectively known as hepatitis, are caused by viruses

Hepatitis A

• Hepatitis A virus causes infectious hepatitis which is transmitted via the oral-fecal route as a result of close contact such as in day-care centers. • The virus is also spread by sexual contact and in contaminated food. • Rarely (in fewer than 1% of cases) is HAV spread by blood products, blood transfusions or intravenous drug use.

Hepatitis A

• The most obvious symptom is jaundice. • HAV also causes abdominal pain, nausea and diarrhea. • In addition, the patient may suffer fatigue and fever. • Chronic infections with HAV do not occur but some patients may experience symptoms for up to 9 months.

Hepatitis A

• An ELIZA test for anti-HAV IgM is available. • Diagnosis is also made from the symptoms and the clusters of cases that occur. • The presence of IgG within the first few weeks of infection suggests a prior infection or vaccination.

Hepatitis A

• There is no treatment. • Supportive care should be given. • Hepatitis A immune globulin can be administered early after infection (two weeks) and gives some temporary immunity (up to five months).

SERUM HEPATITIS – HEPATITIS B

• HBV is found worldwide and is a major cause of hepatocellular carcinoma • Serum hepatitis is usually first diagnosed from the clinical symptoms. • Liver enzymes are also detected in the bloodstream during the symptomatic phase

SERUM HEPATITIS – HEPATITIS B

• Supportive care is the major treatment. • Anti-HBV immune globulin is effective soon after exposure. • It can also be given neonatally to children of HBsAg-positive mothers.

Hepatitis B Tx/Prevention

• There are three FDA-approved drugs for treating hepatitis B. – Interferon-alpha 2b (Intron A) – Hepsera (Adefovir Dipivoxil) – Lamivudine (Epivir HBV) – Vaccination is the best prevention

NON-A, NON-B HEPATITIS (NANBH) - HEPATITIS C

• HCV is found worldwide with the highest incidence in southern and central Europe, the Middle East and Japan.

• Symptoms, when they occur, extend from one to more than five months after infection; virus is detectable in the bloodstream during this period.

NON-A, NON-B HEPATITIS (NANBH) - HEPATITIS C

• Symptoms are the first aspect of diagnosis. • These include jaundice, nausea and fatigue accompanied by elevated (at least ten fold) alanine aminotransferase.

NON-A, NON-B HEPATITIS (NANBH) - HEPATITIS C

• Antibodies against HCV are also clearly indicative. • There is a highly specific ELIZA test that detects HCV antibodies; however, these do not appear until eight to twenty weeks after infection which is after the end of the prodromal phase.

NON-A, NON-B HEPATITIS (NANBH) - HEPATITIS C

• The patient should be assessed for chronic liver disease and counseled to avoid behavior, such as alcohol consumption, that may exacerbate liver damage. • Two drugs in combination are recommended in a 24-48 week regimen. These are ribavirin and pegylated interferon alpha-2a and 2b (Peginterferon which has the trade names Pegintron (Schering-Plough) and Pegasys (Roche).

Rabies

• Rabies virus belongs to the family: Rhabdoviridae • Rabies is spread, usually by bites from animals, to other animals and to man. It is thus a zoonotic infection. • Vaccination of animals has reduced the rate of human disease and in the United States there is approximately one case of human rabies per year.

Rabies

• Vaccination, even after exposure, is extremely effective at preventing disease. • Without such treatment, rabies is almost invariably fatal.

• • The patient should receive the vaccine on first visit and day 3,7,14,28 and the rabies IG after exposure. Half of the RIG should be given around the site of the bite/scratch. Dose 20units/kg

ARBOVIRUSES

• The term arboviruses is used to describe viruses from various families which are transmitted via arthropods. • Diseases caused by arboviruses include encephalitis, febrile diseases (sometimes with an associated rash), and hemorrhagic fevers

ARBOVIRUS-ASSOCIATED ENCEPHALITIS

• • • • • • California serogroup / La Crosse encephalitis

St. Louis encephalitis Eastern equine encephalitis Western equine encephalitis Venezuelan equine encephalitis West Nile encephalitis

ARBOVIRUSES ASSOCIATED WITH FEVER OR HEMORRHAGIC FEVER

• •

Colorado tick fever DENGUE VIRUS

• YELLOW FEVER VIRUS (hemorrhagic fever) – found in Africa and South America

Colorado tick fever

• Occurs in the Rocky Mountain States. • It is a mild disease resulting in fever, headache, myalgia and often rash. • The virus is transmitted by ticks. • In diagnosis, the physician must consider the much more serious Rocky Mountain spotted fever (rickettsial disease) which may have similar initial symptoms

Dengue fever

• One of the more rapidly increasing diseases in the tropics and occurs worldwide (50-100 million cases per year). • Every year there are cases of dengue fever imported by travelers into the United States. • Usually illness is ~1-8 days after infection and IgM may not be present until somewhat later. • The infection can sometimes progress to encephalitis/encephalopathy.

Dengue Hemorrhagic Fever (DHF)

• potentially deadly complication of dengue • A large subcutaneous hemorrhage on the upper arm of a patient with dengue hemorrhagic fever

Dengue Hemorrhagic Fever (DHF)

• This is a disease that is only found in Africa and South America. • Infection results in severe systemic disease, hemorrhages, degeneration of the liver, kidney and heart. • • The case-fatality rate can be 50%.

There is an effective vaccine

strain called 17D). (attenuated

Ebola Virus

Ebola is a virus-caused disease limited to parts of Africa. Within a week, a raised rash, often hemorrhagic (bleeding), spreads over the body. Bleeding from the mucous membranes is typical causing apparent bleeding from the mouth, nose, eyes and rectum.

Ebola Virus

• The exact mode of transmission is not understood. • The incubation period appears to be up to 1 week, at which time the patient develops fatigue, malaise,headache, backache, vomiting, and diarrhea.

Ebola Virus

• Within a week, a raised (papular) rash appears over the entire body. • The rash is often hemorrhagic.

• Hemorrhaging generally occurs from the gastrointestinal tract, causing the patient to bleed from both the mouth and rectum. • Mortality is high, reaching 90%. Patients usually die from shock rather than blood loss.

QUESTIONS????