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TWO ON MEASLES (GUINEA-BISSAU, US)

Sunday, 9th of January 2011

CSU 16/2011: TWO ON MEASLES (GUINEA-BISSAU, US): NON-SPECIFIC EFFECTS OF MEASLES VACCINATION/ MEASLES IN THE US DURING THE POST-ELIMINATION ERA


From Guinea-Bissau, suggestive data on the effects of measles vaccination on mortality. From the US, a detailed account of measles epidemiology in the post-elimination period. What is also needed is economic analysis of the yearly cost to the western hemisphere of waiting for the rest of the world to eliminate measles. Full text is at http://jid.oxfordjournals.org/content/202/10/1520.long Good reading. BD

1) NON-SPECIFIC EFFECTS OF STANDARD MEASLES VACCINE AT 4.5 AND 9 MONTHS OF AGE ON CHILDHOOD MORTALITY Abstract below; full text is at http://www.bmj.com/content/341/bmj.c6495.long

NON-SPECIFIC EFFECTS OF STANDARD MEASLES VACCINE AT 4.5 AND 9 MONTHS OF AGE ON CHILDHOOD MORTALITY: RANDOMISED CONTROLLED TRIAL

Peter Aaby, professor12, Cesário L Martins, clinician1, May-Lill Garly, senior researcher12, Carlito Balé, clinician1, Andreas Andersen, statistician12, Amabelia Rodrigues, research director1, Henrik Ravn, senior statistician12, Ida M Lisse, senior registar3, Christine S Benn, senior researcher12, Hilton C Whittle, professor4 + Author Affiliations 1Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau 2Bandim Health Project, Danish Epidemiology Science Centre, Statens Serum Institut, 2300 Copenhagen S, Denmark 3Department of Pathology, Herlev University Hospital, 2730 Herlev, Denmark 4MRC Laboratories, Fajara, POB 273, Gambia Correspondence to: P Aaby p.aaby@bandim.org Accepted 20 September 2010

Abstract

Objective To examine in a randomised trial whether a 25% difference in mortality exists between 4.5 months and 3 years of age for children given two standard doses of Edmonston-Zagreb measles vaccines at 4.5 and 9 months of age compared with those given one dose of measles vaccine at 9 months of age (current policy).

Design Randomised controlled trial.
Setting The Bandim Health Project, Guinea-Bissau, which maintains a health and demographic surveillance system in an urban area. Participants 6648 children aged 4.5 months of age who had received three doses of diphtheria-tetanus-pertussis vaccine at least four weeks before enrolment. A large proportion of the children (80%) had previously taken part in randomised trials of neonatal vitamin A supplementation. Intervention Children were randomised to receive Edmonston-Zagreb measles vaccine at 4.5 and 9 months of age (group A), no vaccine at 4.5 months and Edmonston-Zagreb measles vaccine at 9 months of age (group B), or no vaccine at 4.5 months and Schwarz measles vaccine at 9 months of age (group C).

Main outcome measure Mortality rate ratio between 4.5 and 36 months of age for group A compared with groups B and C.

Secondary outcomes tested the hypothesis that the beneficial effect was stronger in the 4.5 to 9 months age group, in girls, and in the dry season, but the study was not powered to test whether effects differed significantly between subgroups. Results In the intention to treat analysis of mortality between 4.5 and 36 months of age the mortality rate ratio of children who received two doses of Edmonston-Zagreb vaccine at 4.5 and 9 months of age compared with those who received a single dose of Edmonston-Zagreb vaccine or Schwarz vaccine at 9 months of age was 0.78 (95% confidence interval 0.59 to 1.05). In the analyses of secondary outcomes, the intention to treat mortality rate ratio was 0.67 (0.38 to 1.19) between 4.5 and 9 months and 0.83 (0.83 to 1.16) between 9 and 36 months of age. The effect on mortality between 4.5 and 36 months of age was significant for girls (intention to treat mortality rate ratio 0.64 (0.42 to 0.98)), although this was not significantly different from the effect in boys (0.95 (0.64 to 1.42)) (interaction test, P=0.18). The effect did not differ between the dry season and the rainy season. As neonatal vitamin A supplementation is not WHO policy, the analyses were done separately for the 3402 children who did not receive neonatal vitamin A. In these children, the two dose Edmonston-Zagreb measles vaccine schedule was associated with a significantly lower mortality between 4.5 and 36 months of age (intention to treat mortality rate ratio 0.59 (0.39 to 0.89)). The effect was again significant for girls but not statistically significant from the effect in boys. When measles cases were censored, the intention to treat mortality rate ratio was 0.65 (0.43 to 0.99).

Conclusions Although the overall effect did not reach statistical significance, the results may indicate that a two dose schedule with Edmonston-Zagreb measles vaccine given at 4.5 and 9 months of age has beneficial non-specific effects on children’s survival, particularly for girls and for children who have not received neonatal vitamin A. This should be tested in future studies in different locations.

Trial registration Clinical trials NCT00168558.

2) Measles in the United States during the Postelimination Era 1. Amy Parker Fiebelkorn, 2. Susan B. Redd, 3. Kathleen Gallagher, 4. Paul A. Rota, 5. Jennifer Rota, 6. William Bellini and 7. Jane Seward + Author Affiliations 1. Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 1. Reprints or correspondence: Amy Parker Fiebelkorn, CDC/NCIRD MS A-47, 1600 Clifton Rd, Bldg 16, Atlanta, GA 30333 (AParker@cdc.gov). 1. Presented in part: 46th annual meeting of the Infectious Diseases Society of America, Washington DC, 25–28 October 2008 (oral presentation); Pediatric Academic Societies Annual Conference, Honolulu, Hawaii, 3–6 May 2008 (platform oral presentation). 

Abstract below; full text is at http://jid.oxfordjournals.org/content/202/10/1520.long

 

Abstract

Background. Measles affected entire birth cohorts in the prevaccine era but was declared eliminated in the United States in 2000 because of a successful measles vaccination program.

Methods. We reviewed US surveillance data on confirmed measles cases reported to the Centers for Disease Control and Prevention and data on national measles-mumps-rubella (MMR) vaccination coverage during postelimination years 2001–2008.

Results. During 2001–2008, a total of 557 confirmed cases of measles (annual median no. of cases, 56) and 38 outbreaks (annual median no. of outbreaks, 4) were reported in the United States; 232 (42%) of the cases were imported from 44 countries, including European countries. Among case-patients who were US residents, the highest incidences of measles were among infants 6–11 months of age and children 12–15 months of age (3.5 and 2.6 cases/1 million person-years, respectively). From 2001 through 2008, national 1-dose MMR vaccine coverage among children 19–35 months of age ranged from 91% to 93%. From 2001 through 2008, a total of 285 US-resident case-patients (65%) were considered to have preventable measles (ie, the patients were eligible for vaccination but unvaccinated). During 2004–2008, a total of 68% of vaccine-eligible US-resident case-patients claimed exemptions for personal beliefs.

Conclusions. The United States maintained measles elimination from 2001 through 2008 because of sustained high vaccination coverage. Challenges to maintaining elimination include large outbreaks of measles in highly traveled developed countries, frequent international travel, and clusters of US residents who remain unvaccinated because of personal belief exemptions.

Measles is a highly infectious, acute viral disease that causes rash, respiratory symptoms, and fever. Severe complications, which may result in death, include pneumonia and encephalitis. In the decade before the national measles vaccine program was implemented in 1963, it was estimated that 3–4 million people in the United States acquired measles each year [1]. Of the ∼500,000 measles cases reported annually, 500 resulted in death, 48,000 resulted in hospitalization, and 1000 resulted in permanent brain damage due to measles encephalitis [1].

Achieving a high level of population immunity is the best way to prevent measles. Accordingly, 2 doses of measles-mumps-rubella (MMR) vaccine are recommended for all US children [2]. The first dose should be administered at 12–15 months of age and the second dose at 4–6 years of age. Laws in every state require age-appropriate vaccination of children enrolled in child care facilities and documentation of evidence of measles immunity at the time of entry into kindergarten or first grade [3]. As the vaccinated cohorts age, all children in kindergarten through grade 12 should be covered by the requirements [3]. For adults without evidence of measles immunity, one dose of MMR vaccine is recommended. Two doses are recommended if the adult is in a high-risk group (ie, healthcare workers, international travelers, or students at post-high school educational institutions) [2].

Because of the success of the measles vaccine program in achieving and maintaining high 1- and 2-dose MMR vaccine coverage in preschool and school-aged children and improved control of measles throughout Central and South America, measles was declared eliminated from the United States in 2000 [4] and from the World Health Organization (WHO) Region of the Americas in 2002 [5]. Elimination is defined as the absence of transmission of endemic disease (ie, no epidemiological or virological evidence that measles virus transmission is continuously occurring in a defined geographical area for ⩾12 months). However, in 2008, it was estimated that there were 20 million cases of measles worldwide and 164,000 related deaths [6]. Importation of measles virus from abroad continues to test the status of elimination in the United States. In this report, we summarize the epidemiology of measles in the United States during measles postelimination years 2001–2008.