Measles: an Overview

Case 1
7 month female From East Rand Presented on 02/10/2003 Previously well Not yet immunised against measles 5 day history upper respiratory tract infection symptoms Rash for 2 days went to clinic Referred to JHB Hospital with serological evidence of measles infection No known contacts Also had vomiting, diarrhoea

On examination
Thriving Colour, hydration adequate Miserable Watering eyes, bilateral inflamed tympanic membranes Rhinitis, nasal discharge Shotty cervical lymphadenopathy Cough, but no respiratory distress or chest signs Diffuse maculopapular rash, confluent areas, starting to turn brown in some areas

Course
Patient admitted to ensure adequate fluid intake Day 2 less vomiting Ruptured left tympanic membrane Discharged on Augmentin, Panado

Case 2
8 year old boy From central JHB Known HIV positive patient Recent history cough, fever, malaise, poor appetite, sores on lips Known TB contact father (on treatment) Investigated for TB 1 month before negative No known measles contacts Apparently immunisations up to date

On examination
Toxic, but not marked respiratory distress Reasonably wellgrown Pink on nasal prong oxygen Dry mucous membranes Generalised lymphadenopathy Not jaundiced Diffuse scars/pigmentation from old rashes/folliculitis Excoriated lesion right forearm not from recent PPD Head and neck Severe conjunctivitis, no discharge Unable to open mouth extensive labial sores Herpes lesions Chest Evidence of right upper lobe, left lingular pneumonia

Cardiovascular system

Mild cor pulmonale Generally tender, 4cm tender hepatomegaly

Abdomen

Central Nervous System

Cooperative Generalised decreased power No neck stiffness No focal signs

Management
Treated for bacterial pneumonia Lasix for cardiac failure Investigated for TB

Course
Deteriorated in ward Day 3 noted to have swollen, red lips, circumoral erythema Discharging eyes, unable to open them ? new rash on trunk difficult to see Ill-looking, more drowsy, withdrawn but rousable Lumbar puncture performed, given Vitamin A, measles serology sent Results Day 6- patient demised; terminal event unknown

Results
02/10/2003

06/10/2003

WCC 10,7 Hb 10,1 Plts 257 CRP 160,3 U&E 128/4,3/96/14/7,9/45

WCC 8,6 Hb 10,5 Plts 320 CRP 323 CSF no cells, normal, ADA 2,6 Blood cultures negative Sputum negative Tuberculin skin test neg

Measles
(Rubeola)

Measles virus, genus Morbillivirus, family Paramyxoviridae One serotype, humans only host Virions spherical structures, 100 250 nm diameter Inner capsid composed of coiled RNA helix, 3 proteins Outer envelope matrix protein bearing haemagglutinin (H) peplomer, fusion (F) protein (NB in cytopathic effects of virus)

Epidemiology
Important cause of childhood mortality in developing countries Before vaccine developed (1963) epidemics every 2 5 years, winter and spring Epidemic - up to half a million cases reported Developing countries mortality rate 1 10% Developed countries 0,3% Much fewer cases since live attenuated virus vaccine developed Developed countries

Measles almost eradicated Outbreaks in older children, young adults, eg. College campuses

Developing countries

Common, endemic, increases in winter and spring First year of life, even 6 months of age Sporadic cases, or outbreaks extensive Epidemics facilitated by inadequate immunity, overcrowding More cases complicated Failure to immunise Primary vaccine failure (5%) Waning immunity (rare)

Epidemics occur due to

Highly contagious, respiratory secretions Contagious from 1-2 days before symptoms, 4 days after onset

of rash

Prodrome most infectious Quarantine period 1 week after rash appears, longer for complicated measles

Pathogenesis
Portal of entry respiratory tract Regional lymph nodes Enters bloodstream reticuloendothelial system (primary viraemia) target organs (secondary viraemia) Target organs epithelial, endothelial cells Eyes, skin, respiratory tract, gastrointestinal tract, including mouth Endothelial cells vasculitis Koplik spots, rash due to immune response to virus in endothelial cells Immunocompromised patients may have no rash

Virus directly invades T lymphocytes lymphopenia Decreases neutrophil function, chemotaxis Decreased T helper cells - decreased reactivity to PPD Fusion protein causes typical multinucleated giant cells; also aids viral spread from cell to cell Damage to entire respiratory tract + immune paresis secondary bacterial infections

Clinical features
Usually symptomatic Incubation period (infection to symptoms) : 9-12 days Prodrome :

Enanthem:

2-4 days Nonspecific symptoms fever, malaise, anorexia, headache Classical triad cough, coryza, conjunctivitis (with photophobia, lacrimation) Koplik spots Just before rash appears 1-2 mm, bluish-white, bright red background Buccal mucosa, opposite 2nd molars Pathognomonic for measles Disappear soon after rash appears Entire buccal, labial mucosa may be reddened

Exanthem: Erythematous, non-pruritic, maculopapular Hairline, behind ears trunk limbs, including palms, soles Confluent, blotchy Most ill at this time Day 4 starts to fade (in order of appearance), turns brownish, desquamates Fever settles after 4-5 days if persists, suspect secondary infection Lymphadenopathy, splenomegaly, diarrhoea, vomiting Chest Xray may be abnormal, even in uncomplicated cases Entire illness 10 days

Complications

1)Respiratory Tract
Otitis media most common Laryngitis, croup, bronchitis due to measles itself Secondary pneumonia viral,bacterial Primary giant cell pneumonia due to measles (rare) immunocompromised, malnourished patients Reactivation of TB

2)Gastrointestinal Tract
Gastroenteritis can be severe, especially in already malnourished patients Protein-losing enteropathy Mouth reactivation of Herpes severe stomatitis Hepatitis, ileocolitis, appendicitis, mesenteric adenitis

3)Eye

4)CNS

Malnourished especially at risk Keratitis, keratoconjunctivitis Cause of blindness 3rd world Vitamin A preventive role in respect of infection Encephalitis uncommon Fever, headache, drowsiness, coma, seizures Earlier - direct viral effect in CNS Later immune response causing demyelination Significant morbidity, permanent sequelae mental retardation, epilepsy Rarely transverse myelitis Subacute sclerosing panencephalitis extremely rare, 6-10 years after infection. Progressive dementia, fatal. Interaction of host with defective form of virus

5)Other

Glomerulonephritis, myocarditis, postinfective thrombocytopenic purpura

Lab findings
FBC, differential lymphopenia, neutropenia U&E deranged due to dehydration Raised transaminases Measles encephalitis raised protein, lymphocytes in CSF Virus detection

Serology

Microscopy of respiratory epithelial cells (throat swab) giant cells Immunofluorescence detects Measles antigens Culture virus from respiratory secretions/ urine (1-2 weeks) IgM (1-2 days after onset of rash) IgG (rises after 10 days)

Differential Diagnosis
Classic Measles Koplik spots, coryza, cough, conjunctivitis Kawasaki disease, Scarlet fever, Ebstein Barr virus, Toxoplasmosis, drug reaction, Mycoplasma History of immunisation important

IMMUNITY TO MEASLES

Cell-associated virus Protection antibody-mediated Recovery cell-mediated Immunity usually lifelong Passive maternal transfer of IgG should protect up to 1 year Developing countries higher viral burden + accelerated degradation of antibodies (malnutrition, HIV, chronic immune stimulation) at risk much earlier

Rationale for vaccination strategies (developing countries):

Higher risk during 1st year BUT lower rates of seroconversion (60% - 6 months, 80% - 9 months, 95% - 15 months) 1st vaccine at 9 months 2nd at 18 months NOT a booster rather a second chance at seroconversion

Developed countries routine MMR at 15 months, 2nd MMR at 45 years, or 12 years The Vaccine:

Live attenuated virus Schwarz egg most common Edmonston Zagreb (EZ) human diploid cell culture Subcutaneous Side effects occasional fever (5-7 days later), transient rash Cold chain maintenance NB

Contraindications Severe hypersensitivity to egg protein give EZ instead Allergy to Neomycin Severe immunosuppression chemotherapy, congenital immune deficiencies. NOT HIV (unless intercurrent severe febrile illness) Pregnancy teratogenic

Defer

for 3 months after receiving immune globulin for 6 weeks after receiving blood products for 3 months after stopping immunosuppressive treatment Must give HIV patients asymptomatic and symptomatic, malnourished patients, TB patients Failures Primary failure 5% Faulty storage Pre-existing antibodies (maternally derived) Simultaneous administration of vaccine and immunoglobulin

Who is susceptible?
Consider susceptible unless:

Post-exposure

Proof of receipt of 2 doses of live vaccine, or 1 after 1st birthday Proof of previous diagnosed measles infection Laboratory evidence of immunity

Vaccinate within 72 hours of exposure Immune globulin between 72-96 hours after exposure Treatment Supportive, symptom-directed Antibiotics for otitis media, pneumonia High doses Vitamin A in severe/ potentially severe measles/ patients less than 2 years

Measles in the HIV patient

Lower response to vaccine May acquire lower titres of antibody from mother, higher rate of degradation of maternally acquired antibodies More likely malnourished, more susceptible to severe infection, complications, higher mortality May have had TB reactivate If suspecting TB, PPD before vaccine (anergy up to 1 month after) Measles may hasten progression of HIV