Measles Flashcards
Measles family and structure
Genus Morbillivirus - Rinderpest & distemper viruses
Family: Paramyxoviridae
Enveloped (-)ss non-segmented RNA
24 genotypes, currently only 3 exist/circulate
Vaccine strain - Genotype A, EDMONSTON strain.
The RNA genome of the virus codes 6 main proteins Nucleoprotein (N), Phosphoprotein (P), Matrix protein (M), Fusion protein (F), Hemagglutinin (H), and Large Protein (L),[11] which represents RNA dependent RNA polymerase (RdRp). The viral genome also codes two non-structural proteins C and V. These non-structural proteins are innate immunity antagonists; they help the virus to escape host immune response.
Baltimore class: V
Measles pathogenesis and receptor
Receptor: 1. Signalling lymphocyte activation molecule family member 1 (SLAMF1 AKA CD150) expressed by thymocytes, dendritic cells, Haematopoetic cells, macrophages, T&B cells.
- Nectin cell adhesion molecule (poliovirus receptor-related 4 or PVRL4) is another receptor. Expressed by keratinocytes and endothelial cells - rash because of this.
Entry though CD150 receptors on alveolar macrophages and dendritic cells in the lung & myeloid or lymphoid cells in the conjunctiva.
Replicates in BM, thymus, spleen, tonsils, LNs, Bronchus associated lymphoid tissue. Spreads to other organs through circulating CD150 immune cells.
Measles R0
12 to 18
Measles incubation & infectious period
6 to 21 days
Infectious period: 4 days before to 4 days after onset of rash
Measles clinical syndrome stages
- Regular: stages:
A. Incubation 6 to 21 days - entry, replication, viraemia & dissemination, second viraemia + prodrome
B. Prodrome 2 to 4 days - fever, malaise, and anorexia, followed by conjunctivitis, coryza, and cough.
C. Enanthem - Koplik spots (grains of salt on a red background) lasting 12 to 72 hours.
D. Exanthem 2 to 4 days after fever - erythematous, maculopapular, blanching rash, which classically begins on the face and spreads cephalocaudally and centrifugally to involve the neck, upper trunk, lower trunk, and extremities. The rash usually lasts 6 to 7 days and fades in the order it appeared
E. Recovery
Measles clinical variants
- Modified measles (Breakthrough Measles) — Modified measles is an attenuated infection that occurs in individuals with pre-existing measles immunity (either via wild-type disease or vaccination). It is similar to classic measles except the clinical manifestations are generally milder and the incubation period is longer (17 to 21 days). Individuals with modified measles are not highly contagious.
Seen in: transplacental Ab transfer, HNIG recipients, vaccination without high enough titres, prior measles. - Atypical measles - Atypical measles refers to measles virus infection among individuals immunized with the killed virus vaccine, which was used in the United States between 1963 and 1967; atypical measles is now rare. The killed virus vaccine sensitized the recipient to measles virus antigens without providing full protection [6].
Individuals with atypical measles develop high fever and headache 7 to 14 days after exposure to measles. Atypical measles is characterized by higher and more prolonged fever [27]. A maculopapular rash develops two to three days later, beginning on the extremities (instead of the head as seen with typical measles) and spreading to the trunk. The rash may involve the palms and soles and tends to spare the upper chest, neck, and head [7]. The rash may be vesicular, petechial, purpuric, or urticarial; it may have a hemorrhagic component.
Measles complications
- Immune suppression and secondary infection
- Diarrhoea
- Pneumonitis
- Encephalitis — Encephalitis occurs in up to 1 per 1000 measles cases.
- Acute disseminated encephalomyelitis — Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease that occurs in about 1 per 1000 measles cases. ADEM is thought to be a postinfectious autoimmune response
- Subacute sclerosing panencephalitis — SSPE is a fatal, progressive degenerative disease of the central nervous system that usually occurs 7 to 10 years after natural measles virus infection. Its pathogenesis is not well understood but may involve persistent infection with a genetic variant of measles virus within the central nervous system. In general, patients with SSPE are ≤20 years and become ill 7 to 10 years after natural measles infection. Measles infection at an early age is a risk factor for SSPE; about half of patients with SSPE had measles before the age of two years. The serum anti-measles antibody concentration is elevated, and cerebrospinal fluid analysis shows elevated protein concentration and detectable anti-measles antibody. Incidence 1 in 10,000.
- Measles inclusion body encephalitis (MIBE) - rare. Occurs within few months of infection/vaccination in individuals with T cell immunity defect. Presents with seizures. Measles RNA UNDETECTABLE in CSF, and diagnosis is based on biopsy or INTRA-THECAL abx testing. High mortality and no treatment.
Stages of SSPE
SSPE has been divided into the following stages:
●Stage I – Stage I consists of insidious development of neurologic symptoms such as personality changes, lethargy, difficulty in school, and strange behavior. Stage I may last from weeks to years.
●Stage II – Stage II is characterized by myoclonus, worsening dementia, and long-tract motor or sensory disease. The patient eventually develops a highly characteristic form of myoclonus in which massive myoclonic jerks occur approximately every 5 to 10 seconds. Stage II usually lasts 3 to 12 months.
●Stages III and IV – Stages III and IV are characterized by further neurologic deterioration with eventual flaccidity or decorticate rigidity and symptoms and signs of autonomic dysfunction. Myoclonus is absent. Stage IV is a vegetative state. Death usually occurs during stage IV but is possible in any of the stages
Measles testing
Preferred sample: Oral fluid - rub swab along gum line for 2 mins
IgM - 90% by D3 rash
IgG
PCR followed by genotyping - wildtype vs vaccine strain if taken <D7 rash
Serum:
IgG EIA
IgM mu capture assay
Immunocompromised measles contact
SEE IMAGE IN ALBUM
Group A: These individuals should be able to develop and maintain adequate antibody from any prior successful vaccination or infection and can therefore be managed on the basis of evidence of protection at any time
Urgently assess need for IVIG - IgG testing.
IVIG most effective within 72 hours but up to 6days.
Born before 1970 ONLY if IgG negative or equivocal NOT if not tested (assume immune).
Between 1970-1990, IVIG if IgG negative/equivocal with history of measles/vaccination OR IgG negative/equivocal/not tested within 6 days with no history of measles/vaccination.
> 1990 - IVIG if IgG negative/equivocal with history of infection/vaccination OR
IgG negative/equivocal/not tested within 6 days with history of one measles containing vaccine OR
UNVACCINATED (No testing needed).
Group B includes individuals who are unlikely to have developed or maintained adequate antibody levels from past exposure or vaccination.
This group can be further subdivided into:
B (i) individuals who can be managed based on a measles IgG test at the time of exposure or at any point since the end of treatment or diagnosis.
Test for IgG within 3 days. IVIG if so IgG neg/equivocal or not tested within 3 days in the context of no previous IgG after diagnosis/treatment of immunosuppressive condition.
B (ii) individuals who require IVIG following an exposure WITHOUT the need for testing within 72 hours
For immunosuppressed patients where exposure is recognised late or who are found to be antibody negative or equivocal between 6 and 18 days after exposure, discussion with the specialist caring for the individual should take place, and IVIG may be considered in order to attenuate infection. Where a second exposure occurs more than 3 weeks after a first dose of immunoglobulin, a further dose of immunoglobulin will need to be considered
Measles seroprevalence by age
Seroprevalence studies have shown that less than 1% of individuals born before 1970 and less than 10% born between 1970 and 1989 are antibody negative to measles
Measles exposure in pregnancy
SEE IMAGE IN ALBUM
Born before 1990: History of measles infection - Assume immune
No history of measles infection - Test and administer HNIG within 6 days only if measles antibody negative
History of 2 measles containing vaccines- Assume immune
Born 1990 or later: History of 2 measles vaccines- Assume immune
History of one measles vaccine- Test and administer HNIG within 6 days only if measles antibody negative
Unvaccinated- Test and administer HNIG if measles antibody negative. If not possible to test within 6 days of exposure, offer HNIG.
Measles contact infants
SEE IMAGE IN ALBUM
Under 6 months - HNIG as maternal antibodies interfering with the response to MMR vaccine
Infants aged 6 to 8 months who are household contacts of a case and therefore have a higher intensity exposure should be given HNIG due to the increased risk of more severe disease.
Infants aged 6 to 8 months who have exposures in non-household settings are less likely to have the intensity of exposure to develop severe disease and so should receive MMR vaccine
Infants aged 9 months or older should receive MMR vaccine
MMR should ideally be given within 3 days of exposure. Offering HNIG between 3 and 6 days after exposure is unlikely to offer substantial additional benefit in immunocompetent infants. Where exposure is likely to be ongoing (for example following a single case in a nursery or during a community outbreak), MMR offered beyond 3 days may provide protection from subsequent exposures.
PEP after inadvertent MMR
Pregnant women do not require post-exposure prophylaxis if they are inadvertently given MMR
Immunosuppressive - manage as if exposed to measles
IVIG & HNIG dosing in measles
Based on testing results of products from 3 manufacturers the mean content of measles antibody by plaque neutralisation varies from 4 to 34 IU/ml (80 to 330 IU/g) for IVIG. A minimum protective dose of approximately 11 IU/kg measles antibody should therefore be achievable using a dose of 0.15 g/kg of IVIG.
HNIG (Subham):pregnant women: approximately 3,000mg
infants: 0.6ml/kg up to a maximum of 1,000mg
