Viral Infections of the Skin and Mucus

Membranes

Maculopapular Rash Measles virus Rubella virus Parvovirus Human Herpes 6

Vesicular Rash Herpes simplex virus Varicella zoster virus Coxsakievirus

Measles Measles virus is a paramyxovirus

Paramyxoviruses : Enveloped virus, ssRNA genome as a single piece. The family includes parainfluenza virus, mumps virus, measles virus

and respiratory syncytial virus. Parainfluenza and mumps virus have a surface hemagglutinin and

neuraminidase, while measles have a hemagglutinin, but not neuraminidase.

The virion structure includes: Spikes F protein Matrix protein M, below the envelope

Only one serotype

Measles Disease

Acute febrile illness, mostly in childhood

Incubation period: 10 – 12 days

Onset is flu-like: high fever, cough, conjunctivitis

Koplik's spots: red spots with bluish-white centre on the buccal mucosa

1 – 2 days later, acute symptoms decline with appearance of a widespread maculopapular rash

Over 10 – 14 days, recovery is usually complete as the rash fades

Complications

Giant cell pneumonia, more common in adults

Otitis media

Post-measles encephalitis

Subacute sclerosing panencephalitis (SSPE): progressive and fatal degenerative disease within the infected cells, there is a defective form of the virus

which because it can not produce functional M protein, is not released as complete virus from the cells.

Laboratory Diagnosis

Most cases are diagnosed clinically

NPA, immunofluorescence

EpidemiologyEpidemiology

Transmission: person to person by respiratory droplets. Malnutrition contributes to high mortality.

ControlControl

Live attenuated vaccine, combined with mumps and rubella (MMR)

Administration: between 12 – 18 months.

Rubella (German Measles)

Rubella Virus Classified as togavirus ssRNA virus with an envelope pleomorphic in appearance, 50 – 60 nm in diameter nucleocapsid is icosahedral in symmetry ssRNA is infective and replication occurs in the

cytoplasm three major polypeptides: C and envelope

glycoproteins E1 and E2 single serotype

Postnatal Rubella

Incubation period: 12 – 21 days Macular rash, appears first on the face, then

spreads to the trunk and limbs Minor pyrexia, malaise and lymphadenopathy

with suboccipital nodes most commonly enlarged and tender

Arthralgia is uncommon in children, but may occur in up to 60% of adult females, involving the fingers, wrists, ankles and knees

Encephalitis and thrombocytopenia are rare complications

Pathogenesis

Virus is transmitted by air-borne route URT Viremia

Skin, joints, placenta cross the barrier

Infect fetal differentiating cells Early in pregnancy: this will cause congenital

abnormalities

Laboratory Diagnosis

Clinical diagnosis is unreliable Investigation by virus isolation is not indicated (unreliable

and time-consuming) Serological diagnosis is the method of choice, detecting

rubella specific IgG and rubella specific IgM. These tests are also used for screening to ascertain susceptibility and whether rubella immunization is indicated.

Congenital rubella syndrome: serological testing for specific IgM. Maternal IgM does not cross the placenta so detection of specific IgM is diagnostic of intrauterine infection

Control

Attenuated live vaccine (MMR) Seroconversion occurs in over 95% Protection persists for more than 20 years Administration in pregnancy is contra-indicated Pregnancy should be avoided for the month

following vaccination

Human Parvovirus

Only parvovirus B19 is the cause of diseases in humans

Genus: Erythrovirus

The Virus

20 – 25 nm in diameter icosahedral symmetry, no envelope the capsid consists of two proteins, VP1 and VP2 specific viral receptors such as blood group P

antigen; explains narrow host range infection is followed by life-long immunity Genome: ssDNA

Replication

Dependent on cellular factors expressed transiently in the cell during late S or early G2 phase of mitosis.

All parvoviruses require dividing cells for replication

Clinical Diseases

Rash illness (Erythema infectiosum) Erythematous maculopapular rash Common in children aged 4 – 11 years Very similar to rubella

Joint disease 80% in adult females 10% in childhood cases arthritis involving small joints of the hands with wrists,

knees and ankles affected in some cases

Aplastic crisis A transient acute event which complicates chronic

hemolytic anemia Fall in hemoglobin Disappearance of reticulocytes from peripheral blood Erythropoiesis cessation lasts for 5 – 7 days Symptoms of worsening anemia B19 infection is responsible for 90% of the cases Occurs most commonly in children with sickle cell

anemic

B19 in the immunocompromized Persistent infection that leads to persistent anemia

Laboratory Diagnosis

Virus detection Serum,

detecting viral antigens using ELISA detecting viral genome using nucleic acid hybridization

and PCR

Antibody detection Recent infection can be diagnosed by detecting

B19-specific IgM or increasing amounts of specific IgG.

Epidemiology

Endemic throughout the year in temperate climates

Transmission occurs by respiratory route

High-titre viremia enables transmission by blood

Congenital transmission (vertical)

Treatment

Most cases are mild and self-limiting

Aplastic crisis: blood transfusion

Immunosuppressed: blood transfusion and human normal immunoglobulin

Intrauterine infection: intrauterine blood transfusion

Human Herpesvirus 6 (HHV 6)

Sequence analysis revealed two variants: HHV 6A: no clear disease association HHV 6B: exanthema subitum or roseola infantum

Roseola Infantum

The disease is common between 6 months and 3 years

Sudden onset of fever Throat congestion and cervical lymphadenopathy Widespread macular rash occurs in 10% of the

cases Some cases are associated with HHV-7 infection HHV-6 and -7, both infect T lymphocytes

Vesicular Rash

Herpes simplex virus

Varicella zoster virus

Coxsakievirus

Herpes Simplex Viruses Ubiquitous virus, infecting the majority of world’s

population

Two types: HSV-1 and HSV-2

Type 1 is associated primarily with mouth, eye and CNS

Type 2 is found mostly in the genital tract

Transmission: direct contact

Herpes Simplex Structure

Icosahedral virus

Lipoprotein envelope, derived from the nuclear membrane

Genome: linear, ds DNA

Replicate in the nucleus

HSV Glycoproteins At least 11 glycoproteins are known

Three are essential for production of infectious virus:

gB and gD : penetration into the cells

gH: release of the virus

Pathogenesis Primary Infection The typical lesion is the vesicle; ballooning degeneration of

intra-epithelial cells. The roof of the vesicle breaks down, forming ulcer

During the replication phase at the site of entery in the epithelium, virus particles enter through the sensory nerve endings and transported along the axon to the nerve body (neurone) in the sensory (dorsal root) ganglion by retrograde axonal flow. Latent infection occurs in the survived neurons that still harbor the viral genome

Antibodies reduce the severity of the infections, although it does not prevent recurrences.

Latent Infection About 1% of cells in the affected ganglion carry

the viral genome.

Viral DNA exists as free circular episomes (20 copies / cell).

Latency-associated transcripts (LAT) are present

HSV-1: causes latency in trigeminal ganglion HSV-2: causes latency in sacral ganglion

Reactivation Known triggers for recurrences are accompanied by

a local increase in prostaglandin levels and depression of cell-mediated immunity.

Reactivation can be induced by UV light Fever Trauma Stress

Interval between the stimulus and lesion appearance is 2 – 5 days.

Clinical Features Oral infectionOral infection Acute febrile gingivostomatitis in preschool children Vesicular lesions ulcerate rapidly

Skin infectionsSkin infections Herpetic whitlow: primary lesion on the fingers or

thumb of the toddler with herpetic stomatitis, due to autoinoculation. It also occurs as accidental inoculation in health care workers.

Eczema herpeticum: severe form of cutaneous herpes. It may occur in children with atopic eczema.

Clinical Features Eye infectionEye infection Conjunctivitis or keratoconjunctivitis associated with corneal

ulceration. This will result in corneal scarring and vision impairment.

The majority are caused by HSV-1 Most patients with recurring eye disease are aged over 50 years

CNS infectionCNS infection The most likely route of infection is central spread from

trigeminal ganglion HSV encephalitis

CSF collected in the acute stage should be used for PCR amplification of HSV DNA.

More commonly due to HSV-1

Clinical Features Genital tract infectionGenital tract infection

Both types can infect genital tract, but HSV-2 is more common. The lesions are vesicular at first but rapidly ulcerate

Male: affects the glans and shaft of the penis

Female: affects the labia and vagina or cervix Fever and malaise are accompanied by regional

lymphadenopathy, urethritis and vaginal discharge

Clinical Features Recurrent genital herpesRecurrent genital herpes

Can be as frequent as six or more episodes a year.

Attacks are milder and shorter than first episodes

HSV-1 genital infection recurs less often than HSV-2

Either type is capable of transmission from mother to infant. Transplacental passage has been recorded but is very rare. Ascending infection from the cervix is more significant especially when the membranes are ruptured prematurely.

Laboratory Diagnosis

Isolation of HSV in cultures of human diploid fibroblast cells. Growth is rapid. CPE includes rounded, ballooned cells in foci and giant cell formation

Detection of viral antigens in cell (by immunofluorescence), scraped from the base of lesions

Detection of amplified viral DNA by PCR in CSF

Giant cell formation induced by Herpes simplex infection

Treatment

Acyclovir: inhibits viral DNA synthesis

Acute HSV infections

Latency is not eradicated by this agent

Prophylactic to prevent reactivation in the immunocompromized (transplant recipients)

Available for topical, oral and intravenous route

Varicella Zoster Virus

Two forms

Primary infection is a generalized eruption (chicken pox)

Reactivation is localized to one or few dermatomes (shingles, Varicella Zoster)

Only one antigenic type

Pathogenesis of Chicken Pox Children, vesicular skin eruption

Virus enters through URT or conjunctiva

The virus causes viremia

The vesicles lie in the middle of the epidermis. The fluid becomes cloudy with the influx of leucocytes. These pustules dry up, scabs form and desquamate.

Lesions in all stages are present at any time while new ones are appearing.

Pathogenesis of Varicella Zoster

VZV stays latent in the sensory ganglia

Reactivation can occur at any age but the rate is much increased in persons aged 60 years or over.

Zoster is usually limited to one dermatome; in adults most commonly in the thoracic or upper lumbar region.

Clinical FeaturesChicken Pox

Incubation period: 14 – 15 days

The patient is infectious for 2 days before and up to 5 days after onset

The rash is most dense on the trunk and head

Macules ---- Papules ---- Vesicles ---- Pustules

Chicken Pox

Complications

Secondary bacterial infection (commonest)

Pneumonia

CNS cerebellar ataxia syndrome acute encephalitits

Herpes Zoster

Reactivated VZV infection

Localized eruption, unilateral, typically confined to one dermatome

Prodromal paraesthesia and pain in the area supplied by affected nerve are common before skin lesions develop

Postherpetic neuralgia Most common complication of zoster 50% risk in patients aged over 60 years pain persisting for 1 month or more after the rash

Herpes Zoster

Ophthalmic zoster Involvement of ophthalmic division of the trigeminal

nerve corneal ulceration, stromal keratitis permanent scarring and loss of sight

Laboratory Diagnosis

Early vesicular lesions are the best diagnostic material

Virus isolation takes from 5 days to 3 weeks

More rapid detection is possible with centrifugation-enhanced cultures (shell vials)

Direct immunofluorescence

VZV DNA amplification by PCR

Treatment

Acyclovir

Given to high-risk of complication Neonates (first 3 weeks of life) Ophthalmic zoster Immunocompromized

Epidemiology Spread: respiratory route, in winter and early spring

Varicella is highly infectious to susceptible close contacts

Mortality is high in normal adults, particularly smokers who develop pneumonia

Zoster is associated with decreased T cell function: Old age Pre-AIDS phase Organ transplant recipients

Control

Passive immunization: varicella zoster immunoglobulin (VZIG): Neonates Non-immune pregnant contacts Immunocompromized contacts

A live attenuated vaccine, IM injection

Coxsackieviruses Picornavirus

Icosahedral, positive sense, linear, ssRNA

Two groups: A and B

Group A: Herpangina (vesicular pharyngitis) Hand – Foot – and – Mouth disease Acute hemorrhagic conjunctivitis

Group B: Pleurodynia (epidemic myalgia) Myocarditis Meningoencephalitis

Herpangina Severe febrile pharyngitis The pharynx is usually hyperemic and discrete

vesicles occur on the posterior half of the palate, pharynx, tonsils or tongue

Self-limited and most frequent in small children Hand – Foot – and – Mouth disease

Oral and pharyngeal ulcerations Vesicular rash on the palm and soles

Hand – Foot – and – Mouth disease