EVERYTHING YOU WANTED TO KNOW ABOUT MEASLES BUT WERE AFRAID TO ASK

Tuesday, 21st of June 2011

• EVERYTHING YOU WANTED TO KNOW ABOUT MEASLES BUT WERE AFRAID TO ASK

Many thanks to the indispensable Jane Wachira, who, on the eve of her holiday, assembled 35 pages of abstracts from the forthcoming supplement to the Journal of Infectious Diseases, with abstracts on all aspects of measles epidemiology, control and eradication.

Many firmly held beliefs will not survive the appearance of this supplement. If you think that measles vaccine efficacy is 85 percent, read the piece by Uzicanin and Zimmermann. If you think that measles eradication is poor bang for the buck, read the piece by Levin and colleagues. If you think that outbreak response immunization comes too little and too late, read the piece by Cairns and colleagues. If you think that measles eradication will undermine health systems, try the piece by Griffiths and colleagues.

 

This week, abstracts on generic global issues. Next week, abstracts on measles in the WHO regions.

Subscribers to JID can access the full text of all articles at

Good reading.

BD

I: INTRODUCTION

 

The Measles Initiative: Moving Toward Measles Eradication

1. 1.   Athalia S. Christie1 and
2. 2.   Andrea Gay2 

- Author Affiliations

1. 1.    ¹International Services, American Red Cross
2. 2.    ²United Nations Foundation, Washington, D.C

Correspondence: Ms Athalia S. Christie, MIA, Senior Technical Advisor, American Red Cross–International Services, NW3-117C, 2025 E St NW, Washington, DC 20006 (christieat@usa.redcross.org).

Abstract

The World Health Assembly should establish a target date for measles eradication based on continued progress toward existing mortality reduction goals. We have a safe, effective, and inexpensive vaccine; a proven elimination strategy; high country demand; and an effective global partnership. Since it was founded in 2001, the Measles Initiative has supported the vaccination of >900 million children in supplementary immunization activities. Largely as a result, global measles deaths decreased by 78% between 2000 and 2008, averting an estimated 4.3 million deaths. The Measles Initiative has exceeded its targets and evolved to address increasingly ambitious goals. The current challenges include a decline in funding and weak routine immunization systems in some countries. Skeptics of measles eradication raise 3 main objections: the yet-to-be-achieved polio eradication goal, the high cost, and the impact on health systems. These are important concerns that can be addressed with judicious program planning. All 6 World Health Organization regions have committed to measles elimination, and 5 have set a target date. The World Health Assembly has endorsed interim targets toward eradication, and an independent global measles advisory group has determined measles can and should be eradicated. A target date for eradication will focus efforts and capitalize on the achievements of the last decade.

http://jid.oxfordjournals.org/content/204/suppl_1/S14.abstract

 

 

PUBLIC HEALTH IMPORTANCE OF MEASLES AND RUBELLA

 

Measles Mortality Reduction Contributes Substantially to Reduction of All Cause Mortality Among Children Less Than Five Years of Age, 1990–2008

1. 1.   Maya M. V. X. van den Ent1,
2. 2.   David W. Brown1,
3. 3.   Edward J. Hoekstra1,
4. 4.   Athalia Christie2 and
5. 5.   Stephen L. Cochi3 

- Author Affiliations

1. 1.    ¹United Nations Children’s Fund (UNICEF), New York, New York
2. 2.    ²International Services, American Red Cross, Washington, DC
3. 3.    ³Global Immunization Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia
4. Correspondence: Maya van den Ent, PharmD, MPH, UNICEF Headquarters, 3 UN Plaza, New York, NY 10017 (mvandenent@unicef.org).

Abstract

Background. The Millennium Development Goal  4 (MDG4) to reduce mortality in children aged <5 years by two-thirds from 1990 to 2015 has made substantial progress. We describe the contribution of measles mortality reduction efforts, including those spearheaded by the Measles Initiative (launched in 2001, the Measles Initiative is an international partnership committed to reducing measles deaths worldwide and is led by the American Red Cross, the Centers for Disease Control and Prevention, UNICEF, the United Nations Foundation, and the World Health Organization).

Methods. We used published data to assess  the effect of measles mortality reduction on overall and disease-specific global mortality rates among children aged <5 years by reviewing the results from studies with the best estimates on causes of deaths in children aged 0–59 months.

Results. The estimated measles-related  mortality among children aged <5 years worldwide decreased from 872,000 deaths in 1990 to 556,000 in 2001 (36% reduction) and to 118,000 in 2008 (86% reduction). All-cause mortality in this age group decreased from >12 million in 1990 to 10.6 million in 2001 (13% reduction) and to 8.8 million in 2008 (28% reduction). Measles accounted for about 7% of deaths in this age group in 1990 and 1% in 2008, equal to 23% of the global reduction in all-cause mortality in this age group from 1990 to 2008.

Conclusions. Aggressive efforts to prevent  measles have led to this remarkable reduction in measles deaths. The current funding gap and insufficient political commitment for measles control jeopardizes these achievements and presents a substantial risk to achieving MDG4.

 

http://jid.oxfordjournals.org/content/204/suppl_1/S18.abstract

 

 

 

Strategic Planning for Measles Control: Using Data to Inform Optimal Vaccination Strategies

1. 1.   Emily Simons1,
2. 2.   Molly Mort2,
3. 3.   Alya Dabbagh1,
4. 4.   Peter Strebel1 and
5. 5.   Lara Wolfson3 

- Author Affiliations

1. 1.    ¹Expanded Programme on Immunization, Department of Immunization, Vaccines and Biologicals
2. 2.    ²Consultant to Program for Appropriate Technology in Health
3. 3.    ³Global Influenza Programme, Department of Health, Security, and Environment, World Health Organization, Switzerland
4. Correspondence: Emily Simons, MHS, 20 Ave Appia, 1211 Geneva 27, Switzerland (simonse@who.int).

Abstract

Background. In response to repeated requests  for assistance in evaluating the health benefit and cost implications of adjustments to national measles immunization strategies, the World Health Organization (WHO) has developed the Measles Strategic Planning (MSP) tool to harness routinely available data to estimate effectiveness and cost effectiveness of vaccination strategies.

Method. The MSP tool estimates measles  incidence and mortality through a country-specific cohort model, using a probability of infection dependent on population immunity levels. This method approximates measles transmission dynamics without requiring detailed data that would prohibit use in low- and middle-income countries. Coupled with cost data, the tool estimates incremental costs and cost effectiveness of user-defined vaccination strategies over 5–10 year planning periods.

Results. The MSP tool produces valid  estimates of measles incidence in settings with low to moderate vaccination coverage. Early adopters report that the tool facilitates decision making by minimizing the amount of time required to assess the impact of vaccination strategies on population immunity.

Conclusions. By clearly illustrating what  vaccination strategies can effectively protect against measles at the least cost to immunization programs, the MSP tool supports evidence-based decision making for effective and comprehensive measles control.

http://jid.oxfordjournals.org/content/204/suppl_1/S28.abstract

 

 

Should Outbreak Response Immunization Be Recommended for Measles Outbreaks in Middle- and Low-Income Countries? An Update

1. 1.   K. Lisa Cairns1,
2. 2.   Robert T. Perry1,
3. 3.   Tove K. Ryman1,
4. 4.   Robin K. Nandy2 and
5. 5.   Rebecca F. Grais3 

- Author Affiliations

1. 1.    ¹Global Immunization Division, US Centers for Disease Control and Prevention, Atlanta, Georgia
2. 2.    ²UNICEF, New York, New York
3. 3.    ³Epicentre, Paris, France

Correspondence: K. Lisa Cairns, MD, MPH, MS E-05, 1600 Clifton Rd, Atlanta, GA 30306 (kfc4@cdc.gov).

Abstract

Background  Measles caused mortality in . >164,000 children in 2008, with most deaths occurring during outbreaks. Nonetheless, the impact and desirability of conducting measles outbreak response immunization (ORI) in middle- and low-income countries has been controversial. World Health Organization guidelines published in 1999 recommended against ORI in such settings, although recently these guidelines have been reversed for countries with measles mortality reduction goals.

Methods  We searched literature published . during 1995–2009 for papers reporting on measles outbreaks. Papers identified were reviewed by 2 reviewers to select those that mentioned ORI. World Bank classification of country income was used to identify reports of outbreaks in middle- and low-income countries.

Results  We identified a total of 485 . articles, of which 461 (95%) were available. Thirty-eight of these papers reported on a total of 38 outbreaks in which ORI was used. ORI had a clear impact in 16 (42%) of these outbreaks. In the remaining outbreaks, we were unable to independently assess the impact of ORI.

Conclusions These findings generally . support ORI in middle- and low-income countries. However, the decision to conduct ORI and the nature and extent of the vaccination response need to be made on a case-by-case basis.

http://jid.oxfordjournals.org/content/204/suppl_1/S35.abstract

 

 

 

 

II: FEASIBILITY OF MEASLES ERADICATION

 

Biological Feasibility of Measles Eradication

1. 1.   William J. Moss1 and
2. 2.   Peter Strebel2 

+ Author Affiliations

1. 1.    ¹Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
2. 2.    ²World Health Organization, Geneva, Switzerland
3. Correspondence: William J. Moss, MD, MPH, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 (wmoss@jhsph.edu).

Abstract

Recent progress in reducing global measles mortality has renewed interest in measles eradication. Three biological criteria are deemed important for disease eradication: (1) humans are the sole pathogen reservoir; (2) accurate diagnostic tests exist; and (3) an effective, practical intervention is available at reasonable cost. Interruption of transmission in large geographical areas for prolonged periods further supports the feasibility of eradication. Measles is thought by many experts to meet these criteria: no nonhuman reservoir is known to exist, accurate diagnostic tests are available, and attenuated measles vaccines are effective and immunogenic. Measles has been eliminated in large geographical areas, including the Americas. Measles eradication is biologically feasible. The challenges for measles eradication will be logistical, political, and financial.

http://jid.oxfordjournals.org/content/204/suppl_1/S47.abstract

 

 

Comparing Measles With Previous Eradication Programs: Enabling and Constraining Factors

1. 1.   Robert Keegan1,
2. 2.   Alya Dabbagh2,
3. 3.   Peter M. Strebel2 and
4. 4.   Stephen L. Cochi3 

+ Author Affiliations

1. 1.    ¹Independent consultant, Atlanta, Georgia
2. 2.    ²Department of Immunization, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland
3. 3.    ³Global Immunization Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia
4. Correspondence: Peter M. Strebel, MBChB, MPH, IVB/EPI, World Health Organization, 20 Ave Appia, CH-1211 Geneva 27, Switzerland (strebelp@who.int).

Abstract

Background. Five major disease eradication  initiatives were initiated during the second half of the 20th century. The enabling and constraining factors—political, social, economic, and other—for these previous and current eradication programs can inform decision making regarding a proposed measles eradication initiative.

Methods.We reviewed the literature on the  yaws, malaria, smallpox, guinea worm, and polio eradication programs and compared enabling and constraining factors for each of these programs with the same factors as they relate to a possible measles eradication initiative.

Results. A potential measles eradication  program would enjoy distinct advantages in comparison with earlier eradication programs, including strong political and societal support, economic analyses demonstrating a high level of cost-effectiveness, and a rigorous upfront process, compared with previous eradication initiatives, that has validated the feasibility of achieving measles eradication. However, increasing population density, urbanization, and wars/civil conflicts will pose serious challenges.

Conclusions. Measles eradication will be  very challenging but probably not as difficult to achieve as polio eradication. Measles eradication should be undertaken only if the commitments and resources will be adequate to meet the political, social, economic, and technical challenges.

http://jid.oxfordjournals.org/content/204/suppl_1/S54.abstract

 

Is There Enough Vaccine to Eradicate Measles? An Integrated Analysis of Measles-Containing Vaccine Supply and Demand

1. 1.   Graegar Smith1,
2. 2.   Joshua Michelson1,
3. 3.   Rohit Singh1,
4. 4.   Alya Dabbagh2,
5. 5.   Edward Hoekstra3,
6. 6.   Maya van den Ent3 and
7. 7.   Apoorva Mallya4 

+ Author Affiliations

1. 1.    ¹Oliver Wyman, Chicago, Illinois
2. 2.    ²Department of Immunization, Vaccines, and Biologicals, World Health Organization, Geneva, Switzerland
3. 3.    ³United Nations Children's Fund, New York
4. 4.    ⁴Global Health Delivery, Bill & Melinda Gates Foundation, Seattle, Washington
5. Correspondence: Graegar Smith, MBA, Oliver Wyman, 155 N Wacker Drive, Ste 1500, Chicago, IL 60606 (graegar.smith@oliverwyman.com).

Abstract

Responding to regional advancements in combating measles, the World Health Organization in May 2008 called for an assessment of the feasibility of measles eradication, including whether sufficient vaccine supply exists. Interviews with international health officials and vaccine-makers provided data for a detailed model of worldwide demand and supply for measles-containing vaccine (MCV). The study projected global MCV demand through 2025 with and without a global eradication goal. The study found that 5.2 billion MCV doses must be administered during 2010–2025 to maintain current measles programs, and 5.9 billion doses would likely be needed with a 2020 eradication goal; in the most intensive scenario, demand could increase to 7.5 billion doses. These volumes are within existing and planned MCV-manufacturing capacity, although there are risks. In some markets, capacity is concentrated: Supply-chain disruptions could reduce supply or increase prices. Mitigation strategies could include stockpiling, long-term contracts, and further coordination with manufacturers.

http://jid.oxfordjournals.org/content/204/suppl_1/S62.abstract

 

 

 

 

Risk Analysis for Measles Reintroduction After Global Certification of Eradication

1. 1.   Raymond Sanders1,
2. 2.   Alya Dabbagh2 and
3. 3.   David Featherstone2 

+ Author Affiliations

1. 1.    ¹Independent consultant, Worcester, United Kingdom
2. 2.    ²World Health Organization, Department of Immunization, Vaccines and Biologicals, Geneva, Switzerland
3. Correspondence: Raymond Sanders, Ph.D, 72, Henwick Rd, Worcester, WR2 5NT, United Kingdom (ray@raysanders.co.uk).

Abstract

Background.  Measles virus will continue to  exist after certification of global eradication as virus stocks and infectious materials held in laboratories, in persistently and chronically infected individuals, and possibly in undetected foci of transmission. A literature search was undertaken to identify and evaluate the main risks for reintroduction of measles transmission in the absence of universal measles immunization.

Methods.  A qualitative risk assessment was  conducted following a series of literature searches using the PubMed database.

Results. If the criteria for global  certification of eradication are stringent and require rigorous validation, then the risk of undetected measles transmission after certification is very low. Risk of unintentional reintroduction from any source, including persistent infections and laboratory materials is low to very low but depends on the extent of measles vaccine use. If immunization levels decrease, measles will become a credible agent for bioterrorism through intentional release.

Conclusions. Posteradication risks are low  and should not deter any attempt at measles eradication. More information on measles transmission dynamics and the role of atypical infections is required to determine requirements for global certification of eradication. Posteradication risks would be minimized through development and implementation of an international risk management strategy, including requirements for a posteradication vaccine stockpile.

http://jid.oxfordjournals.org/content/204/suppl_1/S71.abstract

 

 

 

How Can Measles Eradication Strengthen Health Care Systems?

1. 1.   Ulla K. Griffiths1,
2. 2.   Sandra Mounier-Jack1,
3. 3.   Valeria Oliveira-Cruz1,
4. 4.   Dina Balabanova1,
5. 5.   Piya Hanvoravongchai2 and
6. 6.   Pierre Ongolo3 

+ Author Affiliations

1. 1.    ¹Department of Global Health and Development, London School of Hygiene and Tropical Medicine, United Kingdom
2. 2.    ²Department of Global Health and Development, London School of Hygiene and Tropical Medicine, Bangkok, Thailand
3. 3.    ³Centre for Development of Best Practices in Health, Yaoundé Central Hospital, Cameroon
4. Correspondence: U. K. Griffiths, MSc, Dept of Global Health and Development, London School of Hygiene and Tropical Medicine, 5–17 Tavistock Place, London WC1H 9SH, UK (ulla.griffiths@Ishtm.ac.uk).

Abstract

Elimination and eradication initiatives are generally delivered through a vertical approach, which can potentially hamper health systems. We propose 3 approaches by which a measles eradication initiative can ensure that health systems are left strengthened when the eradication goal has been accomplished. First, focus should be placed on strengthening routine vaccination, which could generate positive trickle-up effects on other primary health care services. Second, increased integration with multifunctional health services should be emphasized. Third, efforts should be made to change traditional donor behavior that prioritizes vaccination campaigns and uses uncoordinated staff incentives.

http://jid.oxfordjournals.org/content/204/suppl_1/S78.abstract

 

Impact of Measles Elimination Activities on Immunization Services and Health Systems: Findings From Six Countries

1. 1.   P. Hanvoravongchai1,
2. 2.   S. Mounier-Jack2,
3. 3.   V. Oliveira Cruz2,
4. 4.   D. Balabanova2,
5. 5.   R. Biellik3,
6. 6.   Y. Kitaw4,
7. 7.   T. Koehlmoos5,
8. 8.   S. Loureiro6,
9. 9.   M. Molla7,

10. H. Nguyen8,

11. P. Ongolo-Zogo9,

12. U. Sadykova10,

13. H. Sarma5,

14. M. Teixeira6,

15. J. Uddin5,

16. A. Dabbagh11 and

17. U. K. Griffiths2 

+ Author Affiliations

1. 1.    ¹Department of Global Health and Development, LSHTM, Faculty of Tropical Medicine, Bangkok, Thailand
2. 2.    ²Department of Global Health and Development, LSHTM, 5-17 Tavistock Place, London, United Kingdom
3. 3.    ³Independent consultant, Geneva, Switzerland
4. 4.    ⁴Independent consultant, Addis Ababa, Ethiopia
5. 5.    ⁵Health Systems and Infectious Diseases Division, International Center for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh
6. 6.    ⁶Instituto de Saude Coletiva, Federal University of Bahia, Salvador, Brazil
7. 7.    ⁷Department of Health Management, Environmental Health and Behavioural Sciences, School Of Public Health, Addis Ababa University, Ethiopia
8. 8.    ⁸Department of Epidemiology, Hanoi School of Public Health, Vietnam
9. 9.    ⁹Centre for Development of Best Practices in Health, Yaoundé Central Hospital, Avenue Henri Dunant, Cameroon

10.  ¹⁰Dushanbe, Tajikistan

11.  ¹¹WHO, Geneva, Switzerland

1. Correspondence: Piya Hanvoravongchai, MD, MSc, ScD, LSHTM, 9th Floor, Anekprasong Building, Faculty of Tropical Medicine, 420/6 Rajvithi Road, Bangkok 10400, Thailand (piya.hanvoravongchai@lshtm.ac.uk).

Abstract

Background. One of the key concerns in  determining the appropriateness of establishing a measles eradication goal is its potential impact on routine immunization services and the overall health system. The objective of this study was to evaluate the impact of accelerated measles elimination activities (AMEAs) on immunization services and health systems in 6 countries: Bangladesh, Brazil, Cameroon, Ethiopia, Tajikistan, and Vietnam.

Methods.  Primary data were collected from  key informant interviews and staff profiling surveys. Secondary data were collected from policy documents, studies, and reports. Data analysis used qualitative approaches.

Results. This study found that the impact of  AMEAs varied, with positive and negative implications in specific immunization and health system functions. On balance, the impacts on immunization services were largely positive in Bangladesh, Brazil, Tajikistan, and Vietnam, while negative impacts were more significant in Cameroon and Ethiopia.

Conclusions. We conclude that while weaker  health systems may not be able to benefit sufficiently from AMEAs, in more developed health systems, disruptions to health service delivery are unlikely to occur. Opportunities to strengthen the routine immunization service and health system should be actively sought to address system bottlenecks in order to incur benefits to eradication program itself as well as other health priorities.

http://jid.oxfordjournals.org/content/204/suppl_1/S82.abstract

 

 

Impact of Measles Eradication Activities on Routine Immunization Services and Health Systems in Bangladesh

1. 1.   Tracey Pérez Koehlmoos,
2. 2.   Jasim Uddin and
3. 3.   Haribondu Sarma 

+ Author Affiliations

1. 1.    Health Systems & Infectious Diseases Division, ICDDR,B, Dhaka, Bangladesh
2. Correspondence: Tracey Pérez Koehlmoos, PhD, MHA, Health & Family Planning Systems Program, Health Systems & Infectious Diseases Division, ICDDR,B, 68 Shahed Tajuddin Ahmed, Sarani, Mohakhali, Dhaka-1212 Bangladesh (traceylynnk@hotmail.com).

Abstract

Background. Seroprevalence studies suggest  that vaccination coverage of 90%–95% is needed to eliminate measles. In Bangladesh, routine measles vaccination coverage rates have recently reached 80%–85%. The Government of Bangladesh implemented catch-up vaccination through supplementary immunization activities (SIAs). The aim of the present study was to understand the impact of SIAs on immunization services and the health system.

Methods. The study was conducted at 4 sites,  all of which had relatively low routine vaccination coverage rates. A document review was performed, followed by interviews of key personnel selected by purposive and snowball sampling. A staff profiling survey was also undertaken.

Results.  Despite overall high levels of  immunization, the expanded program on immunization for measles has not reached the coverage levels targeted by the Government of Bangladesh. The first SIAs vaccinated 35 million children, and the second targeted an additional 20 million. According to data and respondents, implementation of the SIAs was successful with sufficient funds being available, although timely disbursement of funds was inadequate in some areas. Staff were well motivated, and additional training helped boost a positive approach to vaccination.

Conclusions. The SIAs had a positive impact  on health and immunization systems and have created a framework on which other health care interventions for bacterial and viral diseases could be based.

http://jid.oxfordjournals.org/content/204/suppl_1/S90.abstract

 

 

III: ECONOMIC STUDIES

Global Eradication of Measles: An Epidemiologic and Economic Evaluation

1. 1.   Ann Levin1,
2. 2.   Colleen Burgess2,
3. 3.   Louis P. Garrison Jr.3,
4. 4.   Chris Bauch4,
5. 5.   Joseph Babigumira3,
6. 6.   Emily Simons5 and
7. 7.   Alya Dabbagh5 

+ Author Affiliations

1. 1.    ¹Independent Consultant, Bethesda, Maryland
2. 2.    ²MathEcology, Phoenix, Arizona
3. 3.    ³Department of Pharmacy, University of Washington, Seattle
4. 4.    ⁴Department of Mathematics and Statistics, University of Guelph, Ontario, Canada
5. 5.    ⁵World Health Organization, Geneva, Switzerland
6. Correspondence: Ann Levin, PhD, 6414 Hollins Dr, Bethesda, MD 20817 (annlevin@verizon.net).

Abstract

Background. Measles remains an important  cause of morbidity and mortality in children in developing countries. Due to the success of the measles mortality reduction and elimination efforts thus far, the WHO has raised the question of whether global eradication of measles is economically feasible.

Methods. The cost-effectiveness of various  measles mortality reduction and eradication scenarios was evaluated vis-à-vis the current mortality reduction goal in six countries and globally. Data collection on costs of measles vaccination were conducted in six countries in four regions: Bangladesh, Brazil, Colombia, Ethiopia, Tajikistan, and Uganda. The number of measles cases and deaths were projected from 2010 to 2050 using a dynamic, age-structured compartmental model. The incremental cost-effectiveness ratios were then calculated for each scenario vis a vis the baseline.

Results. Measles eradication by 2020 was the  found to be the most cost-effective scenario, both in the six countries and globally. Eradicating measles by 2020 is projected to cost an additional discounted $7.8 billion and avert a discounted 346 million DALYs between 2010 and 2050.

Conclusions. In conclusion, the study found  that, compared to the baseline, reaching measles eradication by 2020 would be the most cost-effective measles mortality reduction scenario, both for the six countries and on a global basis.

http://jid.oxfordjournals.org/content/204/suppl_1/S98.abstract

 

 

 

The Cost-Effectiveness of Supplementary Immunization Activities for Measles: A Stochastic Model for Uganda

1. 1.   David Bishai1,
2. 2.   Benjamin Johns2,
3. 3.   Divya Nair1,
4. 4.   Juliet Nabyonga-Orem3,
5. 5.   Braka Fiona-Makmot4,
6. 6.   Emily Simons5 and
7. 7.   Alya Dabbagh5 

+ Author Affiliations

1. 1.    ¹Department of Population, Family, and Reproductive Health
2. 2.    ²Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
3. 3.    ³Health Systems and Services Cluster, World Health Organization (WHO) Uganda Office, Kampala, Uganda
4. 4.    ⁴Immunization Program, WHO Ethiopia Office, Addis Ababa, Ethiopia
5. 5.    ⁵Department of Immunization, Vaccines and Biologicals, WHO Geneva Office, Geneva, Switzerland
6. Correspondence: David Bishai, MD, MPH, PhD, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Room E4622, 615 N Wolfe St, Baltimore, MD 21205 (dbishai@jhsph.edu).

Abstract

Supplemental Immunization Activities (SIAs) have become an important adjunct to measles control efforts in countries that endeavor to achieve higher levels of population immunity than can be achieved in a growing routine immunization system. Because SIAs are often supported with funds that have alternative uses, decision makers need to know how cost-effective they are compared with other options. This study integrated a dynamic stochastic model of measles transmission in Uganda (2010–2050) with a cost model to compare a strategy of maintaining Uganda's current (2008) levels of the first dose of routine measles-containing vaccine (MCV1) coverage at 68% with SIAs with a strategy using the same levels of MCV1 coverage without SIAs. The stochastic model was fitted with parameters drawn from district-level measles case reports from Uganda, and the cost model was fitted to administrative data from the Ugandan Expanded Program on Immunization and from the literature. A discount rate of 0.03, time horizon of 2010–2050, and a societal perspective on costs were assumed. Costs expressed in US dollars (2010) included vaccination costs, disease treatment costs including lost productivity of mothers, as well as costs of outbreaks and surveillance. The model estimated that adding on triennial SIAs that covered 95% of children aged 12–59 months to a system that achieved routine coverage rates of 68% would have an incremental cost-effectiveness ratio (ICER) of $1.50 ($US 2010) per disability-adjusted life year averted. The ICER was somewhat higher if the discount rate was set at either 0 or 0.06. The addition of SIAs was found to make outbreaks less frequent and lower in magnitude. The benefit was reduced if routine coverage rates were higher. This cost-effectiveness ratio compares favorably to that of other commonly accepted public health interventions in sub-Saharan Africa.

http://jid.oxfordjournals.org/content/204/suppl_1/S107.abstract

 

 

Assessing the Cost-Effectiveness of Measles Elimination in Uganda: Local Impact of a Global Eradication Program

1. 1.   Joseph B. Babigumira1,
2. 2.   Ann Levin2,
3. 3.   Colleen Burgess3,
4. 4.   Louis P. Garrison Jr.1,
5. 5.   Chris T. Bauch4,
6. 6.   Fiona Braka5,
7. 7.   William B. Mbabazi6,
8. 8.   Juliet O. Nabyonga6,
9. 9.   Emily Simons1,a and

10. Alya Dabbagh1,a 

+ Author Affiliations

1. 1.    ¹Pharmaceutical Outcomes Research and Policy Program, Department of Pharmacy, University of Washington, Seattle
2. 2.    ²Independent Consultant, Bethesda, Maryland
3. 3.    ³MathEcology LLC, Phoenix, Arizona
4. 4.    ⁴Department of Mathematics and Statistics, University of Guelph, Ontario, Canada
5. 5.    ⁵World Health Organization, Ethiopia Country Office, Addis Ababa
6. 6.    ⁶World Health Organization, Country Office, Kampala
7. 7.    ⁷World Health Organization, Geneva, Switzerland
8. Correspondence: Joseph B. Babigumira, MBChB, MS, PhD, Pharmaceutical Outcomes Research and Policy Program, Dept of Pharmacy, University of Washington, Box 357630, Seattle, WA 98195-7630 (babijo@uw.edu).

Abstract

Background.  Measles control has succeeded  worldwide, and many countries have substantially reduced incidence and mortality. This has led to consideration of the feasibility of measles elimination in Uganda within the context of global eradication. Before an elimination program is initiated, it is important to consider its potential economic impact, including its cost-effectiveness.

Methods. Incremental cost-effectiveness  ratios (ICERs) were estimated for measles mortality reduction and measles elimination in Uganda. A dynamic age-structured compartmental model of measles transmission was used to simulate scenarios and estimate health outcomes and costs. The main outcome measures were costs, measles cases, measles deaths, disability-adjusted life-years (DALYs), and ICERs measured as cost per DALY averted through either the year 2030 or 2050.

Results. Measles elimination by 2020 averted  130,232 measles cases, 3520 measles deaths, and 106,330 DALYs through the year 2030, compared with the next best scenario (95% mortality reduction by 2015), and it was the most cost-effective strategy, with ICERs of $556 per DALY averted (2030 time horizon) and $284 per DALY averted (2050 time horizon).

Conclusions. Measles elimination in Uganda,  as part of a global eradication program, is projected to be highly cost-effective and should be considered among the available policy options for dealing with the disease.

http://jid.oxfordjournals.org/content/204/suppl_1/S116.abstract

 

 

Using Cost-Effectiveness Analysis to Support Research and Development Portfolio Prioritization for Product Innovations in Measles Vaccination

1. 1.   Louis P. Garrison Jr1,
2. 2.   Chris T. Bauch2,
3. 3.   Brian W. Bresnahan1,
4. 4.   Tom K. Hazlet1,
5. 5.   Srikanth Kadiyala1 and
6. 6.   David L. Veenstra1 

+ Author Affiliations

1. 1.    ¹Pharmaceutical Outcomes Research and Policy Program, Department of Pharmacy, University of Washington, Seattle
2. 2.    ²Department of Mathematics and Statistics, University of Guelph, Ontario, Canada
3. Correspondence: Louis P. Garrison, PhD, Pharmaceutical Outcomes Research and Policy Program, University of Washington, 1959 NE Pacific St, Box 357630, Seattle, WA 98195 (lgarrisn@uw.edu).

Abstract

Background. Several potential measles  vaccine innovations are in development to address the shortcomings of the current vaccine. Funders need to prioritize their scarce research and development resources. This article demonstrates the usefulness of cost-effectiveness analysis to support these decisions.

Methods. This study had 4 major components:  (1) identifying potential innovations, (2) developing transmission models to assess mortality and morbidity impacts, (3) estimating the unit cost impacts, and (4) assessing aggregate cost-effectiveness in United Nations Children’s Fund countries through 2049.

Results. Four promising technologies were  evaluated: aerosol delivery, needle-free injection, inhalable dry powder, and early administration DNA vaccine. They are projected to have a small absolute impact in terms of reducing the number of measles cases in most scenarios because of already improving vaccine coverage. Three are projected to reduce unit cost per dose by $0.024 to $0.170 and would improve overall cost-effectiveness. Each will require additional investments to reach the market. Over the next 40 years, the aggregate cost savings could be substantial, ranging from $98.4 million to $689.4 million.

Conclusions. Cost-effectiveness analysis can  help to inform research and development portfolio prioritization decisions. Three new measles vaccination technologies under development hold promise to be cost-saving from a global perspective over the long-term, even after considering additional investment costs.

http://jid.oxfordjournals.org/content/204/suppl_1/S124.abstract

 

IV: MEASLES VACCINE SAFETY AND EFFECTIVENESS

 

Field Effectiveness of Live Attenuated Measles-Containing Vaccines: A Review of Published Literature

1. 1.   Amra Uzicanin and
2. 2.   Laura Zimmerman 

+ Author Affiliations

1. 1.    Centers for Disease Control and Prevention, Atlanta, Georgia
2. Correspondence: Amra Uzicanin, MD, MPH, Centers for Disease Control and Prevention, 1600 Clifton Rd, Mail Stop E-03, Atlanta, GA 30333 (aau5@cdc.gov).

Abstract

Background.  Information on measles vaccine  effectiveness (VE) is critical to help inform policies for future global measles control goals.

Methods. We reviewed results of VE studies  published during 1960–2010.

Results. Seventy papers with 135 VE point  estimates were identified. For a single dose of vaccine administered at 9–11 months of age and ≥12 months, the median VE was 77.0% (interquartile range [IQR], 62%–91%) and 92.0% (IQR, 86%–96%), respectively. When analysis was restricted to include only point estimates for which vaccination history was verified and cases were laboratory confirmed, the median VE was 84.0% (IQR, 72.0%–95.0%) and 92.5% (IQR, 84.8%–97.0%) when vaccine was received at 9–11 and ≥12 months, respectively. Published VE vary by World Health Organization region, with generally lower estimates in countries belonging to the African and SouthEast Asian Regions. For 2 doses of measles-containing vaccine, compared with no vaccination, the median VE was 94.1% (IQR, 88.3%–98.3%).

Conclusions. The VE of the first dose of  measles-containing vaccine administered at 9–11 months was lower than what would be expected from serologic evaluations but was higher than expected when administered at ≥12 months. The median VE increased in a subset of articles in which classification bias was reduced through verified vaccination history and laboratory confirmation. In general, 2 doses of measles-containing vaccine provided excellent protection against measles.

http://jid.oxfordjournals.org/content/204/suppl_1/S133.abstract

 

 

Persistence of Vaccine-Induced Measles Antibody Beyond Age 12 Months: A Comparison of Response to One and Two Doses of Edmonston-Zagreb Measles Vaccine Among HIV-Infected and Uninfected Children in Malawi

1. 1.   Ashley Fowlkes1,
2. 2.   Desiree Witte2,
3. 3.   Judy Beeler3,
4. 4.   Susette Audet3,
5. 5.   Philip Garcia1,
6. 6.   Aaron Curns1,
7. 7.   Chunfu Yang1,
8. 8.   Richard Fudzulani2,
9. 9.   Robin Broadhead2,

10. William J. Bellini1,

11. Felicity Cutts4 and

12. Rita F. Helfand1 

+ Author Affiliations

1. 1.    ¹Centers for Disease Control and Prevention, Atlanta, Georgia
2. 2.    ²College of Medicine, University of Malawi, Blantyre, Malawi
3. 3.    ³Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland
4. 4.    ⁴London School of Hygiene and Tropical Medicine, United Kingdom
5. Correspondence: Ashley Fowlkes, MPH, Centers for Disease Control and Prevention, 1600 Clifton Rd, NE MS A34, Atlanta, GA 30333 (afowlkes@cdc.gov).

Abstract

Background. Previously, we demonstrated that  measles antibody prevalence was lower at age 12 months among children infected with human immunodeficiency virus (HIV) than uninfected children following measles vaccination (MV) at ages 6 and 9 months. Among HIV-uninfected children, measles antibody prevalence was lower among 1- than 2-dose MV recipients. Here, we report results through age 24 months.

Methods.  Children born to HIV-infected  mothers received MV at 6 and 9 months, and children of HIV-uninfected mothers were randomized to MV at 6 and 9 months or MV at 9 months. We followed children through age 24 months. The child's HIV status was determined and measles immunoglobulin G (IgG) level was measured by enzyme immunoassay (EIA) and by plaque reduction neutralization (PRN) on a subset.

Results.  Among HIV-uninfected children, the  difference in measles antibody prevalence at age 12 months between one- and two-dose recipients reported previously by EIA was shown to be smaller by PRN. By age 24 months, 84% and 87% of HIV-uninfected children receiving 1 or 2 doses, respectively, were seroprotected. Only 41% of 22 HIV-infected children were measles seroprotected at age 20 months.

Discussion. Measles seroprotection persisted  through age 24 months among HIV-uninfected children who received 1 or 2 doses of MV. HIV-infected children demonstrated seroprotection through age 12 months, but this was not sustained.

http://jid.oxfordjournals.org/content/204/suppl_1/S149.abstract

 

International Measles Incidence and Immunization Coverage

1. 1.   Robert Hall and
2. 2.   Damien Jolley 

+ Author Affiliations

1. 1.    Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
2. Correspondence: Robert Hall, MBBS MPH, School of Public Health and Preventive Medicine, Monash University, The Alfred Centre, 99 Commercial Rd, Melbourne, Victoria 3004, Australia (robert.hall@monash.edu).

Abstract

Measles is exquisitely sensitive to immunization programs. We investigated the decline in measles incidence after immunization with 1 or 2 doses of measles-containing vaccine (MCV), with or without supplementary immunization activities (SIAs). Using data from the World Health Organization, we modeled the impact of measles immunization using a negative binomial regression model. All countries offer measles immunization, and 192 of 193 countries offer a second dose of MCV (MCV2), using either a routine second dose, SIAs, or both. The incidence of measles fell from a median of 70.9 cases/100,000/year when coverage with a first dose of MCV (MCV1) was in the range of 0%–39% to a median of .9 cases/100,000/year when MCV1 coverage was 90%–100%, in both cases with no MCV2. Further reductions followed the introduction of MCV2 and SIAs. Modeling showed that each 1% increase in MCV1 coverage was followed by a 2.0% decrease in incidence in the same and following years (95% confidence interval [CI], 2.0%–1.9%, and 2.1%–1.9%, respectively). For a second dose, a rise of 1% in MCV2 coverage was followed by a decrease in measles incidence by .4% (95% CI, .3%–.5%) in the same year and .3% (95% CI, .2%–.5%) in the following year. SIAs were followed by decreases of measles incidence by 40.3% (95% CI, 46.3%–33.8%) in the same year and 45.2% (95% CI, 51.1%–48.7%) in the following year. A herd immunity effect was demonstrated with MCV1 coverage of >80%, and SIAs are an extraordinarily effective strategy for measles control.

http://jid.oxfordjournals.org/content/204/suppl_1/S158.abstract Expand+

 

Measles Vaccination in HIV-Infected Children: Systematic Review and Meta-Analysis of Safety and Immunogenicity

1. 1.   Pippa Scott1,
2. 2.   William J. Moss2,
3. 3.   Zunera Gilani2 and
4. 4.   Nicola Low1 

+ Author Affiliations

1. 1.    ¹Division of Clinical Epidemiology and Biostatistics, Institute of Social and Preventive Medicine, University of Bern, Switzerland
2. 2.    ²Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
3. Correspondence: Nicola Low, MD, MSc, FFPH, Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, Bern, CH-3012, Switzerland (low@ispm.unibe.ch.).

Abstract

Background.  Measles control may be more  challenging in regions with a high prevalence of HIV infection. HIV-infected children are likely to derive particular benefit from measles vaccines because of an increased risk of severe illness. However, HIV infection can impair vaccine effectiveness and may increase the risk of serious adverse events after receipt of live vaccines. We conducted a systematic review to assess the safety and immunogenicity of measles vaccine in HIV-infected children.

Methods. The authors searched 8 databases  through 12 February 2009 and reference lists. Study selection and data extraction were conducted in duplicate. Meta-analysis was conducted when appropriate.

Results. Thirty-nine studies published from  1987 through 2008 were included. In 19 studies with information about measles vaccine safety, more than half reported no serious adverse events. Among HIV-infected children, 59% (95% confidence intervals [CI], 46–71%) were seropositive after receiving standard-titer measles vaccine at 6 months (1 study), comparable to the proportion of seropositive HIV-infected children vaccinated at 9 (8 studies) and 12 months (10 studies). Among HIV-exposed but uninfected and HIV-unexposed children, the proportion of seropositive children increased with increasing age at vaccination. Fewer HIV-infected children were protected after vaccination at 12 months than HIV-exposed but uninfected children (relative risk, 0.61; 95% CI, .50–.73).

Conclusions. Measles vaccines appear to be  safe in HIV-infected children, but the evidence is limited. When the burden of measles is high, measles vaccination at 6 months of age is likely to benefit children of HIV-infected women, regardless of the child's HIV infection status.

http://jid.oxfordjournals.org/content/204/suppl_1/S164.abstract

 

 

Safety and Immunogenicity of Early Measles Vaccination in Children Born to HIV-Infected Mothers in the United States: Results of Pediatric AIDS Clinical Trials Group (PACTG) Protocol 225

1. 1.   Sulachni Chandwani1,
2. 2.   Judy Beeler2,
3. 3.   Hong Li3,
4. 4.   Susette Audet2,
5. 5.   Betsy Smith4,
6. 6.   John Moye5,
7. 7.   David Nalin6 and
8. 8.   Keith Krasinski1
9. 9.   for The PACTG 225 Study Team

+ Author Affiliations

1. 1.    ¹Department of Pediatrics, New York University School of Medicine, New York City
2. 2.    ²United States Food and Drug Administration, Bethesda, Maryland
3. 3.    ³Harvard School of Public Health, Cambridge, Massachusetts
4. 4.    ⁴National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
5. 5.    ⁵National Institute of Child Health & Human Development, Bethesda, Maryland
6. 6.    ⁶Former Director, Vaccine Scientific Affairs, Merck Vaccine Division (retired) West Point, Pennsylvania
7. Correspondence: Sulachni Chandwani, MD, Associate Professor of Pediatrics, NYU School of Medicine, 550 First Avenue, 8W46 NB Bldg. New York, NY 10016 (sulachni.chandwani@nyumc.org).

Abstract

Background.PACTG (Pediatric AIDS Clinical  Trials Group) 225, a multicenter, randomized, open-label trial in the United States evaluated reactogenicity and immunogenicity of 2 vaccination regimens: monovalent measles vaccine (Attenuvax) at 6 months of age and measles, mumps, and rubella, live attenuated (MMRII) vaccine at 12 months of age (2D), or only MMRII at 12 months of age (1D) in human immunodeficiency virus–infected (HIV-infected) (POS) and uninfected (NEG) children in the pre–highly active antiretroviral therapy (pre-HAART) period.

Methods. Plaque-reduction neutralization  (PRN) of measles-neutralizing antibody titers were evaluated at study weeks 0, 6, 26, 32, 52, and 130 (∼3 years of age).

Results.The 110 subjects included: 65  2DNEG; 30 1DNEG; 7 2DPOS and 8 1DPOS. Vaccinations (n = 175) were associated with no adverse experiences >Grade 2 except for Grade 3 fever (n = 2, 1 1DPOS and 1 1DNEG). Six weeks after Attenuvax, all 2DPOS subjects (7/7) seroresponded (PRN titers ≥120 mIU/mL) with median titers significantly exceeding 2DNEG titers (2115 vs 628 mIU/mL, respectively; P = .023). At ∼3 years of age, 67% 1DPOS (4/6) and 83% 2DPOS (4/5) subjects maintained titers ≥120 mIU/mL. Prevaccination titers ≥25 mIU/mL among 2DNEG subjects correlated inversely with the likelihood of achieving titers ≥120 mIU/mL (56% vs 90%; P = .004).

Conclusions. Among HIV-infected children  pre-HAART, Attenuvax at 6 months was well tolerated and immunogenic. These data support the current World Health Organization (WHO) recommendation to administer a first dose of measles vaccine at 6 months of age to HIV-infected children.

http://jid.oxfordjournals.org/content/204/suppl_1/S179.abstract

 

 

 

Measles Supplementary Immunization Activities and GAVI Funds as Catalysts for Improving Injection Safety in Africa

1. 1.   Edward J. Hoekstra1,
2. 2.   Maya M. V. X. van den Ent1,
3. 3.   Halima Dao1,
4. 4.   Hala Khalaf2 and
5. 5.   Annika Salovaara2 

+ Author Affiliations

1. 1.    ¹United Nations Children's Fund (UNICEF) Program Division, Health Section, New York, New York
2. 2.    ²UNICEF Supply Division, Copenhagen, Denmark
3. Correspondence: Edward John Hoekstra, MD, MSc, UNICEF Headquarters, 3 UN Plaza, New York, NY 10017 (ehoekstra@unicef.org).

Abstract

Background. In 2000, reuse of disposable  syringes and inadequately sterilized syringes resulted in 39% of all injections being unsafe, causing 22 million infections. We describe the contribution of measles supplemental immunization activities (SIAs) and Global Alliance for Vaccines and Immunisation (GAVI) funding in replacing disposable and sterilizable syringes with auto-disable (AD) syringes to improve injection safety in 39 African countries.

Methods. We assessed trends in nationwide  introduction of AD syringes against measles catch-up SIAs and GAVI funding using World Health Organization/United Nations Children's Fund (UNICEF) Joint Reporting Form for Immunization and UNICEF supply data.

Results. In 19 (49%) of 39 countries, the  measles program catalyzed the introduction of injection safety equipment, including AD syringes and safety boxes, training, and procurement of safety equipment during SIAs. GAVI was catalytic through financial support in 14 countries (36%) for including safe injection equipment in routine immunization. Additionally, GAVI funded 21 countries that had already introduced AD syringes in their national program. UNICEF AD syringe shipments to sub-Saharan Africa increased from 11 million to 461 million from 1997 to 2008. All 39 countries stopped using sterilizable syringes by 2004.

Conclusions. The measles mortality reduction  program and GAVI complemented each other in improving injection safety. All countries continued with AD syringes for immunization after measles catch-up SIAs and GAVI funding ended.

http://jid.oxfordjournals.org/content/204/suppl_1/S190.abstract