VIRAL SYNDROMES

1.         Viral Diseases of the Respiratory Tract

a.            Epidemiology:

i.            respiratory infections are the most common afflictions of humans, and most are caused by viruses.

ii.          children contract on average about half a dozen respiratory illnesses each year, and adults perhaps two or three.

iii.         more serious lower respiratory tract infections tend to occur at the extremes of life, and in those with preexisting pulmonary conditions.

iv.         the most important human respiratory viruses are influenza and respiratory syncytial viruses, the former killing mainly the aged and the latter the very young.

b.            Altogether, there are about 200 human respiratory viruses, falling mainly within six families: orthhomyxoviruses, paramyxoviruses, picornaviruses, coronaviruses, adenoviruses, and herpesviruses.

c.            Immunity against reinfection:

i.            systemic viral infections such as measles generate a strong memory response and prolonged production of IgG antibodies, which protect against reinfections for life.

ii.          in contrast, viruses that cause infection localized to the respiratory tract with little or no viraemia, such as RSV or rhinoviruses, induce only a relatively transient mucosal IgA antibody response and reinfection can occur repeatedly throughout life.

d.         Rhinitis (common cold):

i.          it is marked by copious watery nasal discharge and obstruction, sneezing and perhaps a mild sore throat or cough, but little or no fever.

ii.          all colds are viral.

iii.            rhinoviruses are the major cause with cornonaviruses responsible for another 15%.

iv.         in children, RSV and parainfluenza viruses are responsible for up to half of all upper respiratory tract infections which predispose to otitis media or sinusitis.

v.            repeated viral infections can precipitate recurrent middle ear infections, leading to progressive hearing loss.

e.            Pharyngitis:

i.          upper respiratory tract infections can present as a sore throat, with or without cough, malaise, fever and/or cervical lymphadenopathy.

ii.          primary infections with herpes simplex virus, if delayed until adolescence, presents as a pharyngitis rather than gingivostomatitis.

iii.            infectious mononucleosis is usually seen in adolescents and young adults and is marked by a very pharyngitis; it is caused by Epstein-Barr virus and occasionally with CMV if lacking the sore throat, swollen glands and heterophil antibody.

f.            Laryngotracheobronchitis (Croup):

i.          one of the serious manifestations of parainfluenza and influenza virus infections.

ii.          a young child presents with fever, a ‘barking’ or ‘metallic’ cough, inspiratory stridor, and respiratory distress, sometimes progressing to complete laryngeal obstruction and cyanosis.

g.            Bronchiolitis:

i.          RSV is the main pathogen responsible.

ii.          the disease can develop at remarkable speed: breathing becomes rapid and labored, and is accompanied by a persistent cough, expiratory wheezing, cyanosis and marked emphysema.

iii.         the infant may die overnight and hence RSV is one of the causes of sudden infant death syndrome.

h.            Pneumonia:

i.          viruses are uncommon causes of pneumonia in immunocompetent adults, but are very important in young children.

ii.          RSV and parainfluenza virus are responsible for 25% of all pneumonitis in infants in first year of life while 20% can be ascribed to perinatal infection with CMV.

iii.         CMV can also caused lethal pneumonia in immunocompromised patients, as may measles, varicella and adenoviruses.

iv.         the patient is generally febrile, with a cough and a degree of dyspnea, and auscultation may reveal some wheezing or moist rales.

h.         Table of Respiratory viral diseases:

2.         Viral Gastroenteritis

a.         Not all viruses found in the feces cause gastroenteritis; some cause ‘silent’ infections of the gastrointestinal tract, which is their portal of entry to the body (e.g. many enteroviruses and adenoviruses.

b.            Gastroenteritis vies with upper respiratory infection for the mantle of the commonest of all infectious diseases and is the greatest cause of death – it is estimated that 5-10 million children die each year in the Third World from diarrheal diseases.

c.            Rotaviruses are the main culprit, infecting young children and causing severe diarrhea which may last up to a week and lead to dehydration requiring fluid and electrolyte replacement.

d.            Astroviruses are less virulent and common, causing a mild form of enteritis with watery diarrhea, mainly in young children and in the immunosuppressed.

e.         Table of Viral gastroenteritis:

3.         Viral Diseases of the Central Nervous System

a.         Cause of Viral CNS diseases:

i.          most meningitis and almost all encephalitis is of viral etiology.

ii.            infections of the CNS arise, in the main, as a rare complication of a primary infection established elsewhere in the body which spreads to the brain, usually via the bloodstream.

iii.            sometimes they occur following reactivation of a latent herpesvirus or papovavirus infection.

iv.            overwhelming disseminated infections acquired perinatally may also involve the brain.

b.         Certain viruses have a predilection for particular parts of the CNS, and the clinical signs of the resulting disease reflect this:

i.          most enteroviruses do not go beyond the meninges.

ii.            polioviruses invade anterior horn of spinal cord and motor cortex of cerebrum.

iii.         rabies singles out Ammon’s horn and herpes simplex virus the temporal lobes.

c.         Some viruses lyse neurons directly; others do their damage in more subtle ways, leading to demyelination of nerves.

d.         One must distingusih between neurovirulence, the ability to cause neurologic disease, and neuroinvasiveness, the ability to enter the nervous system:

i.          mumps virus displays high neuroinvasiveness, but low neurovirulence.

ii.          herpes simplex virus displays low neuroinvasiveness, but high neurovirulence in that it often causes devastating damage.

e.            Significance of Blood-brain barrier:

i.          exclude viruses from CNS and also limits access of lymphoid cells, antibodies, complement, etc.

ii.          hence, the barrier deter virus clearance, accounting for the high frequency with which persistent virus infections involve the CNS.

f.            Meningitis:

i.          viral meningitis is much commoner than bacterial meningitis but is much less severe.

ii.          only meningeal cells and ependymal cells are involved and recovery is almost always complete.

iii.         the patient presents with headache, fever, and neck stiffness, with or without vomiting and/or photophobia.

iv.         lumbar puncture reveals a clear CNS, with near normal protein and glucose concentrations with only a moderate pleocytosis.

v.         the most important etiologic agents are mumps virus and numerous enteroviruses, including all the coxsackie B types, coxsackie A7 and A9, polioviruses and many echoviruses.

vi.         the herpesviruses HSV, CMV and EBV are rare sporadic cases.

g.            Paralysis:

i.            polioviruses remain the major cause of both aseptic meningitis and paralytic poliomyelitis.

ii.            enterovirus 71 and coxsackievirus A7 are rare causes of a paralytic disease.

h.            Encephalitis:

i.          one of the most serious of all viral diseases.

ii.          the illness often begins like meningitis with fever, headache, vomiting, and neck rigidity, but alteration in the state of consciousness indicates that the brain parenchyma itself is involved.

iii.         initially lethargic, the patient becomes confused with stuporose.

iv.         ataxia, seizures, and paralysis may develop before the victim lapses into a coma and dies.

v.            survivors may often be left with a legacy of permanent sequelae, including mental retardation, epilepsy, paralysis, deafness or blindness.

vi.         after encephalitogenic mosquito-borne viruses, mumps is a common cause of encephalitis, but it is generally mild.

vii.        HSV is a common cause of severe sporadic encephalitis, infecting both neurons and glia to produce a focal encephalitis localized to the temporal lobes.

I.            Postinfectious encephalomyelitis:

i.          a severe demyelinating condition of the brain and spinal cord which occurs as an occasional complication following a few days after measles, varicella, rubella or mumps.

ii.          may be an autoimmune disease in which viral infection provokes an immunogenic attack on myelin.

j.            Guillain-Barre Syndrome:

i.          an acute inflammatory demyelinating polyradiculoneuropathy which follows exposure to any one of several viruses.

ii.            Epstein-Barr virus is most commonly implicated, with Guillain-Barre syndrome appearing 1-4 weeks after infectious mononucleosis.

iii.         partial or total paralysis develops in more than one limb; complete recovery occurs within weeks, but 15% retains residual neurologic disability.

k.         Reye’s Syndrome: a postinfectious encephalopathy with a 25% case-fatality rate which follows influenza or chickenpox in children.

l.          Chronic demyelinating disease:

i.          SSPE is a rare late sequel to measles, whereas progressive rubella panencephalitis is an even rarer but similar demyelinating persistent infection.

ii.            progressive multifocal leukoencephalopathy is a different type of demyelination seen when AIDS or immunosuppression for renal transplantation reactivates infection with the human polymavirus JC.

m.        AIDS Encephalopathy (AIDS Dementia Complex): over 50% of AIDS patients develop progressive dementia with cerebral involvement, myelopathies or sensory neuropathies.

n.            Tropical Spastic Paraparesis:

i.            infection with human T-cell leukemia virus type 1 is usually subclinical.

ii.          rarely, after an incubation period of 40 years, a subacute disease of the thoracic spinal cord can develop involving progressive paralysis of the legs together with impotence and incontinence.

o.         Table of Viral Diseases of CNS:

4.         Viral Skin Rashes

a.         Viruses that infect the skin, such as papillomaviruses, poxviruses, and recurrent herpes simplex, produce relatively localized crops of lesions and few if any systemic symptoms.

b.         Others, such as those causing the childhood exanthemata, produce a generalized rash as a part of a wider clinical syndrome that follows a systemic infection.

c.            Maculopapular rashes:

i.          macules are flat, colored spots; papules are slightly raised from the surface of the skin but contain no expressible fluid.

ii.          virus is not shed from the lesions of maculopapular rashes.

iii.         many such rashes may in fact result from a hypersensitivity response to the virus growing in cells of the skin of capillary endothelium.

d.         Viruses causing maculopapular rashes:

i.          the exanthem of measles consists of flat reddish brown macules which coalesce to form large blotches; after the rash fades on day 5 or 6 the skin retains a brownish stain for a time then undergoes desquamation.

ii.          in contrast, the exanthem of rubella consists of much smaller pink macules which tend to remain discrete, giving the rash a fine appearance.

iii.         in, erythema infectiosum, the child first develops flushed red cheeks, contrasting pallor around the mouth, then a rubelliform eruption on the limbs which develops a lacelike appearance as it fades.

e.         Viruses causing vesicular rashes:

i.          vesicles are blisters, containing clear fluid from which virus can readily be isolated.

ii.          a generalized vesicular rash in a febrile child today is usually chickenpox.

iii.         the lesions occur in crops, initially concentrated on the trunk, then spreading centrifugally, each vesicle progresses to a pustule and a scab which then falls off.

iv.            however, in the case of disseminated herpes simplex or zoster, the lesions may be widespread throughout the body.

f.            Poxviruses preferentially infect the skin, producing multiple pustular or nodular lesions, as in human monkeypox and molluscum contagosium, respectively, or usullay single lesions as in orf, cowpox and tanapox.

g.         In papillomavirus infections, the papilloma, or wart, is a benign hyperplastic growth, usually multiple, occurring in crops on the skin or mucous membranes.

h.         Table of viruses causing skin rashes:

5.         Viral Haemorrhagic Fevers

a.         The haemorrhagic fevers share the same common characteristic of widespread hemorrhage from the body’s epithelial surfaces, including the internal mucosae such as the gastrointestinal tract as well as the skin.

b.         The skin rash is often a mixture of pinpoint hemorrhages (petechiae) and massive bruising (ecchymoses).

c.            Thrombocytopenia and leukopenia are almost always present with a hypovolemic shock without major blood loss which may lead to death within hours.

d.         Severe liver damage, extensive bleeding, and disseminated intravascular coagulation are causes of the high mortality of these diseases.

e.         Table of viruses causing haemorrhagic fevers:

6.         Viral Genitourinary Infections

a.         Genital warts, caused most commonly by the human papillomaviruses HPV-6 and HPV-11, can take the form of prolific excrescenes on the external genitalia, perineum, vaginal introitus, penis or anus (condyloma accuminatum).

b.         Certain oncogenic HPV types, types 16 and 18, produce cervical dysplasia which may progress over many years to invasive cancer.

c.         Several other human pathogens are shed in semen and in female genital secretions and are transmitted by sexual intercourse but cause no disease in the genital tract itself.

d.         These viruses are HIV, HTLV-1, hepatitis B and C viruses, cytomegalovirus and Epstein-Barr virus.

e.         Acute hemorrhagic cystitis, an unusual disease of young boys, has been associated principally with adenoviruses 11 and 21.

f.            Glomerulonephritis is sometimes observed as a manifestation of immune complex disease in chronic hepatitis B infections.

g.            Cytomegalovirus persists asymptomatically in renal tubules, from which cytomegalic cells and virus and shed into the urine.

h.         When primary infection or reactivation of CMV occurs during renal transplantation, rejection of the graft may be accelerated.

I.          The human polymaviruses BK and JC also persist in the urinary tract and are reactivated by immunosuppression for renal transplanation.

j.            Hemolytic-uremic syndrome is characterized by acute microangiopathic hemolytic anemia, intravascular coagulopathy, and impaired renal function has been associated with various enteroviruses.

k.         Viral diseases of Genitourinary tract:

7.         Viral Diseases of the Eye

a.            Conjunctivitis is a transient feature of a number of common childhood exanthemata such as measles, rubella, and certain enteroviral and arboviral infections.

b.            Keratoconjunctivitis:

i.            potentially more dangerous, as it involves the cornea.

ii.            adenoviruses 8 and 37 are major causes of epidemic keratoconjunctivitis, which spreads readily by contact to adults and usually involves only one eye.

iii.         the main cause of sporadic keratoconjunctivitis and commonest infectious cause of blindness in the Western world is herpes simplex virus.

iv.            pathogenic dendritic ulcers develop on the cornea and if infection progresses to involve the stroma beneath, the immunologic reaction may lead to keratitis, scarring and loss of vision.

v.         when herpes zoster involves the fifth cranial nerve, ophthalmic zoster can cause lasting damage to the eye.

c.            Retinopathy, glaucoma, microphthalmia and cataracts are the major eye abnormalities encountered in the congenital rubella syndrome; total or partial blindness may result.

d.         Table of viral infections of the eye:

8.         Viral Arthritis

a.            Arthritis, usually accompanied by fever and myositis, with or without a rash, is a common presentation of infections of many arboviruses.

b.         Arthritis is a less prominent feature of rubella but is common in adult females following either natural infection or rubella vaccine.

c.            Polyarthralgia is also an important feature of infection with the parvovirus B19, especially in women and may smolder on for months.

d.         In all these diseases, the polyarthritis tends to flit from one joint to another, involving principally the extremities such as the hands; only rarely does it persist for more than a few weeks.

e.         Much less frequently, ephemeral arthritis is seen in mumps, varicella, and coxsackievirus infection.

d.         The arthralgia sometimes observed in the prodromal stages of hepatitis B is immunologically mediated.

e.         Table of viral arthritis:

9.         Viral Carditis

a.            Coxsackie B viruses and certain other enteroviruses such as coxsackieviruses A4 and A16 and echoviruses 9 and 22 are the most important causes of carditis.

b.         The disease may present as myocarditis, percarditis, or cardiomyopathy with a greatly dilated heart.

c.            Recrudescences quite often occur, leading to permanent myocardial damage, cardiomegaly, or congestive heart failure.

d.         The primary disease episode occurs at any age but especially in athletic adolescent or young adult males.

e.            Coxsackie B viruses and echovirus 11 can infect the newborn prenatally, natally or postnatally, resulting in the encephalomyocarditis syndrome.

f.          The syndrome is characterized by fever, dyspnea, cyanosis, tachycardia, abnormal heart sounds, and electrocardiographic changes and is accompanied by meningoencephalitis.

g.         Table of Viral causes of carditis

10.       Viral Pancreatitis and Diabetes

a.         Mums can be complicated by severe pancreatitis and coxsackie B viruses or other enteroviruses have been incriminated also.

b.         Mumps infections often affect the beta cells of the pancreas.

c.         The association of IDDM with particular HLA types has encouraged a hypothesis that pancreatic infection with any of perhaps several viruses may trigger autoimmune destruction of beta cells.

11.            Congenital and Perinatal Viral Infections

a.            Parvovirus B19, which replicates only in cycling cells such as embryonic cells or bone marrow, appears to be responsible for the death of at least a proportion of the fetuses that are miscarried or stillborn with hydrops fetalis.

b.         Rubella during the first 3-4 months of pregnancy inflicts severe teratogenic effects.

c.            Perinatal infection with cytomegalovirus induces cytomegalic inclusion disease.

d.         Table of congenital and perinatal viral diseases: