Measles Do we immunize earlier?

Tan Kah Kee MD Dept of Pediatrics Hospital Tuanku Jaafar Seremban

Outline
Measles infection Measles vaccination Measles vaccine strategies

Measles infection

Measles Infection
Highly contagious viral illness

First described in 7th century

Near universal infection of childhood in prevaccination era Frequent and often fatal in developing countries

Measles Virus
Paramyxovirus (RNA)
Hemagglutinin important surface antigen

One antigenic type

Rapidly inactivated by heat and light

Measles Epidemiology
Reservoir : Human Transmission : Airborne Communicability : 4 days before to 4 days after rash onset

Measles Pathogenesis
Respiratory transmission of virus Replication in nasopharynx and regional lymph nodes Primary viremia 2-3 days after exposure

Secondary viremia 5-7 days after exposure with spread to tissues

Measles Clinical Case Definition

Generalized rash lasting >3 days, and Temperature >38.30 C , and Cough or coryza or conjunctivitis

Measles Clinical Features

Incubation period 10-14 days Stepwise increase in fever to 390 C or higher TRIAD : cough , coryza , conjunctivitis Koplik spots

Measles Rash
History is unreliable! (unlike chickenpox) 2-4 days after prodrome, 14 days after exposure Maculopapular, becomes confluent Begins on face and head Persists 5-6 days Fades in order of appearance

Measles Laboratory Diagnosis

Isolation of measles virus from a clinical specimen (e.g., nasopharynx, urine) Significant rise in measles IgG by any standard serologic assay (e.g., EIA, HA) Positive serologic test for measles IgM antibody : 75% +ve > 3 days & 100% +ve > 7 days (taken 1st 3 days may have false ve in 20%)

Measles Complications
Condition Diarrhea Otitis media Pneumonia Encephalitis Death Hospitalization
60% of deaths due to pneumonia CFR of encephalitis 15% & high proportion of permanent brain damage
Australian Immunization Guide 2013

% reported
8 7 6 0.1 0.2 18

Measles Complications by Age Group

30 25 20

Pneumonia

Hospitalization

Percent

15 10 5 0 <5 5-19 20+

Age group (yrs)

Vitamin A for measles

Reduces mortality due to measles At least two doses to reduce measles mortality by 62% (95% CI 1982). Infants younger than 6 months 50,000 IU/day PO for 2 doses Age 6-11 months - 100,000 IU/day PO for 2 doses Older than 1 year - 200,000 IU/day PO for 2 doses
Sudfeld CR et al. Int J Epidemiol 2010;39

Measles vaccines

Measles Vaccines
1963 1965 1967 1968 1971 Live attenuated and killed vaccines Live further attenuated vaccine Killed vaccine withdrawn Live further attenuated vaccine (Edmonston-Enders strain)(Msia:1982) Licensure of combined measlesmumps-rubella vaccine Two dose schedule MMR(USA)(Msia:2002)

1989

Measles Vaccine
Composition : Live virus Efficacy : 95% (range , 90-98%) at 1 yr old Duration of immunity : Lifelong Recommended schedule : 2 doses Administered as MMR

MMR Vaccine Failure

Measles, mumps, or rubella disease (or lack of immunity) in a previously vaccinated person 2%-5% of recipients do not respond to the first dose
Caused by antibody, damaged vaccine Most persons with vaccine failure will respond to second dose

Measles Mumps Rubella Vaccine

12 months is the recommended and minimum age MMR given before 12 months should not be counted as a valid dose Revaccinate at >12 months of age

Second dose of Measles vaccine

Intended to produce measles immunity in those who failed to respond to the first dose(primary vaccine failure) May boost antibody titers(secondary vaccine failures due to waning immunity)

2nd dose MMR

1st dose of MMR at 12-15 mth 2nd dose at 4-6 yrs 2nd dose may be given > 28 days after 1st dose

MMR Adverse Reactions

Fever : 5-15% Rash : 5% Joint Sx : 25% Thrombocytopenia : < 1 per 30,000 doses Parotitis : rare Encephalopathy : < 1 per 1,000,000 doses

Measles vacccine strategies

Measles Incidence vs MCV1 vaccination coverage, Malaysia (1970 2011)

700
120

600

100

500
80

400
60

300

National SIA: 8-15 y; 93%

40

200
20

100

Incidence per 1mil. pop

Vaccination coverage

Ministry of Health Malaysia

Distribution of Measles Virus genotype, 2010 & 2011

1G3

1A

6D9
1G3 1G3 1D9 1D9 14D9 5D8 5D9 1G3 2D8 1G3 1A 1D9
A case import from Indonesia 2010 A case import from Singapore 2011

1B3

2010 D9, B3, G3 2011 D9, D8

Ministry of Health Malaysia

Measles Incidence* Western Pacific Region 2008

* per million population

LEGEND: < 1.0 (22) 1.0 4.9 (4) 5.0 9.9 (3) 10.0 19.9 (4) 20.0 29.9 (0) 30.0 39.9 (0) 40.0 49.9 (0) 50.0 (3)
Ministry of Health Malaysia Source: WPRO measles-rubella monthly country reports and WHO-UNICEF Joint Reporting Form (data for 2008)

Measles Incidence* Western Pacific Region 2012

* per million population

LEGEND: < 1.0 (30) 1.0 4.9 (1) 5.0 9.9 (1) 10.0 19.9 (2) 20.0 29.9 (0) 30.0 39.9 (0) 40.0 49.9 (1) 50.0 (1)
Ministry of Health Malaysia Source: WPRO measles-rubella monthly country reports, data through February 2012

Annualized Incidence = 3.5

Confirmed Measles Cases, by Month of Onset Malaysia 20082012*

250

200

number of cases

150

100

50

Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb 2008 (lab & Epi-linked = 93; clinically = 222) 2009 (Lab & Epi-linked = 50; clinically = 1) 2010(Lab & Epi-linked = 68; clinically = 4) 2011(Lab & Epi-linked = 1378; clinically = 92) 2012
Lab-confirmed Epi-linked Clinically confirmed

Ministry of Health Malaysia

2012 Lab & Epi-Linked=267, Clinically=33

Confirmed Measles Cases, by State Malaysia 20112012*

2011

1 dot = 1 case

Discarded measles per 100K population: 2 1.0 - 1.9 <1

2012

No suspected measles cases

Ministry of Health Malaysia * Source: WPRO measles-rubella monthly country reports, data through February 2012

Lab confirmed and Epi-linked measles cases, by age group and vaccination status, Malaysia, January 2011-February 2012

Ministry of Health Malaysia

Laboratory confirmed and epi-linked measles cases by year of age and vaccination status, Malaysia, January 2011-February 2012

Ministry of Health Malaysia

Accumulation of susceptible pop

MCV1 Coverage
ELB Est 1 - 2 yo Recipent Missed No. <50% 50%-79% 80%-89% 90%-94% >=95% 4367 88758 58869 82746 276113 510853 3788 88417 61691 78876 258129 490900 1378 65035 52317 72796 279828 471354 2410 23382 9374 6080 -21699 19546 4.0 % 63.6 26.4 15.2 7.7

Based on coverage 2011 95% seroconversion rate was not taken into account
Ministry of Health Malaysia

Indicators
No. INDICATORS TARGET 2009 2010 2011

INCIDENCE
1. Confirmed measles cases (confirmed by lab, epidemiologic linkage or clinically) <1/1 mil. 2.0 2.6

55.0

HIGH QUALITY SURVEILLANCE

1 2

Non-measles suspected case 2 / 100,000 % districts reporting 1 / 100,000 non-measles suspected case
Cases investigated within 48 hours after notification

2 kes 80%

7.7 86.7

3.6 93.3

11.7 93.3

80%

35.6

43.8

55.9

Adequate blood specimen within 28 days after rash onset

Ministry of Health Malaysia

80%

96.1

80.4

79.3

Recommendations
Retain 1st dose of MMR at 12 months Advanced 2nd dose MMR to 18 months , instead of Standard 1 Giving additional dose of measles monocomponent vaccine to hot spots at 6 months old not beneficial Efficacy of measles vaccine at 6 mth = 35.7 %
Ministry of Health Malaysia

Kurubi J et al. Trop Med & Int Health 2009;14

Conclusions
Measles is a highly transmissible infection Death mainly due to pneumonia Sequalae due to encephalitis significant Shifting 2nd dose of MMR to 18 mth old may be practical & useful

Ministry of Health Malaysia