The Resurgence of Measles: Guidance for Clinicians (printer-friendly)

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The Resurgence of Measles: Guidance for Clinicians

Kristen A. Feemster, MD, MPH, MSHP Posted: 02/02/2012

Measles Today: A Public Health Threat Measles is one of the most contagious infectious diseases in humans. It is a major contributor to child mortality worldwide and kills approximately 1-3 of every 1000 infected individuals, even in developed countries.[1] An effective vaccine was introduced in the 1960s, and along with global prioritization of measles control initiatives, this advance has significantly reduced the burden of disease. In 1997, 36 million cases and more than 1 million deaths occurred worldwide, but measles now accounts for an estimated 164,000 deaths per year globally. Endemic transmission was declared to be eliminated in the United States and the Americas in 2000.[2-4] This was promising news, yet today, measles is reemerging as a public health threat. As of August 26, 2011, 198 cases and 15 outbreaks of measles were reported in the United States, the largest number of cases seen in this country since 1996.[5-7] In Europe, outbreaks have been ongoing in 36 of the 53 World Health Organization (WHO) European member countries, resulting in almost 30,000 cases in 2011. Measles is now considered endemic in the United Kingdom after being reportedly eliminated as of 1995.[8-10] In Africa, the number of cases increased from 36,000 in 2009 to 172,824 in 2010, and outbreaks were reported in countries with successful measles control programs.[3] Even in countries with widespread vaccine availability and a well-established public health infrastructure, sustaining measles control has become a growing challenge.
The Measles Revival

The reemergence of measles is the result of the confluence of 3 factors: High transmissibility of the measles virus; Increasing rates of vaccine refusal; and Globalization. Without vaccination, almost all susceptible individuals exposed to measles will become infected. Population vaccination rates of at least 90% are required to achieve herd immunity and disrupt sustained transmission.[3,4,11-13] Even in populations with high vaccination coverage, a group of unvaccinated susceptible individuals can reintroduce the virus in a community.[14,15] In the recent outbreaks in the United States, most cases occurred in unvaccinated persons.[5-6] Outbreaks have also been reported in older children and young adults with primary vaccine failure, especially before implementation of the 2-dose vaccine recommendation.[16-20] Maintaining vaccine coverage according to current recommendations is paramount to ensuring population protection. However, vaccine refusal is increasingly contributing to clusters of intentionally unvaccinated individuals. Rates of vaccine refusal, especially in states that permit philosophical exemptions, are increasing, and recent data show significant geographic variation in coverage rates for the measles, mumps, and rubella vaccine (MMR).[21] Of 12 cases in a recent outbreak in California, 75% were children who were intentionally unvaccinated, and most of their parents reported vaccine safety concerns as the reason for vaccine refusal.[14] Recent outbreaks also illustrate the effects of globalization. Measles remains endemic in many countries, including many European countries, making exposure a real possibility for susceptible travelers or visitors. In the United States, 89% of measles cases were imported by returning travelers or recent immigrants.[22-24] The resurgence of measles puts those who cannot be vaccinated at risk, results in significant costs for outbreak investigations and containment activities, and could lead to a resurgence of measles-associated morbidity and
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The Resurgence of Measles: Guidance for Clinicians (printer-friendly)

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mortality in children. Clinicians are at the forefront of recognizing and managing the disease, educating parents and guardians, and implementing vaccination recommendations amid growing concerns about vaccine safety. Measles: A Brief Review Measles is an RNA virus of the Paramyxoviridae family. The virus is transmitted primarily from person to person by means of respiratory droplets or small aerosolized particles. Peak transmission occurs in the late winter and early spring, with epidemics every 2-5 years depending on vaccination coverage rates. After exposure, the virus replicates in respiratory epithelial cells and spreads to local lymph nodes. This is followed by viremia and spread of the virus to lymphoid tissue, gastrointestinal tract, lungs, liver, and skin. Signs and symptoms of infection develop as a result of the host immune response to viral replication at any of these sites, after an incubation period of approximately 10-12 days.[3,4,11] Initial symptoms include fever, cough, coryza, and conjunctivitis. During this time, pathognomonic Koplik spots also may appear on the buccal mucosa (Figure 1).

Figure 1. Koplik spots on the buccal mucosa and tongue during the prodromal stage. Image courtesy of Public Health Images Library, Centers for Disease Control and Prevention (CDC). After 2-4 days, a characteristic erythematous maculopapular rash develops (Figure 2).

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The Resurgence of Measles: Guidance for Clinicians (printer-friendly)

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Figure 2. Measles rash, third day. Image courtesy of Public Health Images Library, CDC. The rash usually begins behind the ears on the face and spreads to the trunk and extremities before fading, sometimes with desquamation, after 3-7 days. Symptoms resolve with no sequelae in most cases, but approximately 40% of infected individuals (especially infants and young children) develop complications. Undernourished children and those with cellular immunity defects are at increased risk for severe disease.
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The complication associated with the most mortality is pneumonia, owing either to the measles virus or to a secondary viral or bacterial infection in the wake of measles-induced suppression of the immune response to other pathogens.[3] Otitis media and diarrhea are other common complications of measles infection. The latter can result in significant malnourishment. Vitamin A deficiency also can develop, which contributes to keratoconjunctivitis and subsequent blindness. Central nervous system (CNS) complications occur rarely but are associated with significant morbidity and mortality. Acute measles encephalitis occurs in 1 of 1000 cases and can lead to permanent neurologic sequelae or death.[3,11,25] The most devastating CNS complication is subacute sclerosing panencephalitis (SSPE), a consequence of persistent measles virus infection. SSPE occurs in approximately 1 of 100,000 affected individuals, although vaccination has rendered this outcome very rare in the United States. When it does occur, SSPE usually does not manifest until several years after primary infection and results in progressive, irreversible, and uniformly fatal neurologic deterioration. Making the Diagnosis Most parents of young children and many pediatricians or primary care providers have never encountered measles; therefore, cases may not be readily recognized. In endemic areas with known active transmission, the diagnosis can be made clinically on the basis of a well-established case definition of fever and maculopapular rash plus cough, coryza, or conjunctivitis.[26,27] However, in nonendemic areas, laboratory testing is recommended to confirm a diagnosis of measles because multiple, more prevalent pathogens also can present with fever and rash. Serology from a serum sample is the most common and simple laboratory test for the diagnosis of measles. Detection of measles-specific IgM or a 4-fold increase in measles-specific IgG between acute and convalescent serum samples are both considered diagnostic of acute infection. IgM is usually undetectable until 4 days after onset of the rash and subsequently declines 4-8 weeks after infection. If IgM testing is performed less than 72 hours after the onset of symptoms, it should be repeated. Measles virus also can be isolated in cell culture from respiratory, nasopharyngeal, conjunctival, blood, or urine specimens. Finally, reverse transcriptase polymerase chain reaction is also available. This test allows genotyping and identification of wild-type vs vaccine-type virus but is also highly sensitive. Measles RNA can persist for months, so a positive test result does not necessarily indicate acute infection.[3,20,25]
What to Do if a Case of Measles Is Suspected

All suspected cases of measles should be reported immediately to the local or state public health department, even while awaiting test results. Vitamin A is the only intervention that has been shown to reduce morbidity and mortality, especially in children younger than 2 years of age. Measles infection is associated with low vitamin A concentrations, which contribute to such complications as keratoconjunctivitis. The effects of vitamin A deficiency are most prominent in developing countries but can also be seen in children from developed countries. The WHO therefore recommends administering a daily dose of 200,000 IU of vitamin A for 2 days to all infected children older than 12 months, regardless of where they live.[3,25] Management is otherwise supportive and aimed at maintaining hydration, but antibiotics may be required for secondary bacterial infection. No antiviral treatment has been approved for measles. Ribavirin has been used in severe cases on the basis of evidence of in vitro susceptibility, but this intervention has not been evaluated systematically.[3,25] Patients who are considered immune: Have a history of natural measles infection; Were born before 1957; Received 2 doses of a measles-containing vaccine at least 28 days apart on or after their first birthday; or Have detectable measles-specific IgG antibodies.
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If a healthy susceptible person is exposed to measles, a measles-containing vaccine should be administered within 3 days of the exposure (in the absence of contraindications). An intramuscular injection of immune globulin can be administered within 6 days of exposure to susceptible close contacts who are younger 12 months, pregnant, or immunocompromised and therefore cannot receive a measles-containing vaccine.[25] More detailed information on postexposure prophylaxis is available through the American Academy of Pediatrics (AAP) Committee on Infectious Diseases.[25] Measles Prevention Prevention of infection is the cornerstone of a successful measles control program, and vaccination is the most effective means of prevention. The first attenuated live virus vaccines were licensed in the United States in 1963. Currently, a live-attenuated vaccine derived from the Moraten strain is the only product used in the United States, in combination with mumps and rubella or with mumps, rubella, and varicella. Measles vaccination is most effective when administered after 12 months of age. Although antibody levels decrease over time, protection seems to persist, except in a small proportion of children who show evidence of primary vaccine failure.[11] A 2-dose program was therefore implemented in the United States in 1989 to capture children who may not have responded to their first vaccination.[17,28] Current vaccine recommendations are summarized in the Table. Table. Current Measles Immunization Recommendations Unimmunized children with no history of disease Routine recommendation: First MMR vaccine dose at 12-15 months of age; second dose at 4-6 years of age Exceptions to routine recommendation: During a measles outbreak or if traveling to an endemica region, the second dose may be given earlier than 4-6 years of age if at least 28 days have passed since the first dose. Infants aged 6-11 months may be given 1 dose of MMR during an outbreak or if traveling to an endemic region. This dose must be repeated at age 12-15 months, and a third dose should be given at age 4-6 years. Catch-up immunization for children aged 7-18 If previously unimmunized, give 2-dose series. Minimum interval years and students > 18 years of age between doses is 28 days. attending college or another institution If a child received only 1 dose after the first birthday, give a second dose of MMR. Any child or adult who has only received 1 Give 2-dose series. Minimum interval between doses is 28 days. MMR dose before the first birthday or who received inactivated vaccine (briefly available 1963-1967) Any child who has received IG or IVIG MMR vaccine should not be administered until 5-6 months after IG administration and 8-11 months after IVIG administration

Data from American Academy of Pediatrics[25] IG = immune globulin; IVIG = intravenous immune globulin; MMR = measles, mumps, and rubella a Endemic refers to a location where there is regular, sustained disease transmission
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The Resurgence of Measles: Guidance for Clinicians (printer-friendly)

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a Endemic refers to a location where there is regular, sustained disease transmission

MMR vaccine is safe, well tolerated, and has few contraindications to administration. The vaccine can cause fever in 5%-15% of children within 6-12 days after administration, as well as rash in less than 5% of recipients. A very small proportion (1 in 25,000 to 1 in 2 million) may develop transient thrombocytopenia. Encephalopathy occurs after fewer than 1 in 1 million doses, which is lower than the incidence of encephalopathy due to unknown causes. Therefore, any reported cases may be coincidentally, and not causally, associated with vaccination. Febrile seizures have been shown to occur at a slightly higher rate after MMR (1 additional episode for every 3000-4000 doses).[11,25] Local hypersensitivity reactions may occur infrequently. Severe allergic reactions or anaphylaxis are very rare (approximately 3.5 episodes per 1 million doses).[11] Contraindications to vaccination include pregnancy, immunodeficiencies associated with increased risk for viral infections, recent administration of immunoglobulin or high-dose corticosteroids, and a history of anaphylaxis to a measles-containing vaccine. Individuals with a history of anaphylaxis to either gelatin or neomycin, which are present in trace amounts in the vaccine, should consult with an allergist or receive the vaccine only in a place where a severe reaction could be managed. Anaphylaxis to neomycin is very rare. Individuals with hypersensitivity to neomycin usually present with contact dermatitis, which is not a contraindication to vaccination. A history of febrile seizures is not a contraindication to vaccination, but families should be counseled about the small increased risk. Finally, children with HIV/AIDS can be vaccinated if they are not severely immunocompromised.[11,25] Despite decades of experience with MMR, the vaccine has been the subject of substantial controversy. The biggest controversy, and one that has most significantly influenced acceptance of MMR, is the now-refuted causal association between the MMR vaccine and autism. This controversy was sparked by a 1998 publication in The Lancet describing 12 children with inflammatory bowel dysfunction and developmental disorders.[29] Most of these children had received MMR vaccine, and the study hypothesized that vaccination caused their bowel dysfunction, which in turn caused autism. This hypothesis has been refuted by multiple studies, including a review performed by the Immunization Safety Committee of the Institute of Medicine, and the study publication was retracted by The Lancet. [30-36] Despite this overwhelming evidence, concerns about vaccine safety persist.[37] How to Respond to Parents' Vaccine Concerns One of the most important things you can do to confront the reemergence of measles is to ensure that the children you see are vaccinated. Parents or other guardians are looking for information to make the best decisions to protect their child's health. Studies show that most parents believe that vaccines are beneficial but are still concerned about vaccine safety.[37] Therefore, the decision involves a risk-benefit assessment -- what is the risk that my child will get a disease and have a poor outcome, compared with the risk of my child having an adverse event after receiving the vaccine?[38] For MMR, this can be a tough calculation. Most parents have never experienced measles, so they are likely to consider their child to be at low risk. They may not appreciate how easy it is for measles outbreaks to occur when immunization rates fall by even a small degree. In addition, the potential severity of the disease is underappreciated. Despite the evidence supporting the safety of the MMR vaccine and refuting the link between MMR and autism, parents can still easily access misinformation from various sources that can foster lingering doubt. Many of these information sources are compelling, and it can be difficult to counter them with scientific data.[39,40] Still, studies show that most parents do trust their child's healthcare provider over other sources when it comes to vaccine information.[41] Several articles concerning communication with vaccine-hesitant parents have been published recently.[39,40,42-44] The most important goal is to maintain an open dialogue that acknowledges and respects parents' concerns while providing accurate information about both the disease and the vaccine. Here is an approach that builds on this body of work and incorporates this goal: Be proactive -- begin a dialogue about vaccines early to provide multiple opportunities for parents or guardians to express concerns and for you to answer questions and provide information.[45]
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to express concerns and for you to answer questions and provide information.[45] Know the disease -- because many pediatric clinicians have not encountered measles, it can be difficult to communicate the risks for infection. Use numbers to help provide perspective with respect to risk -- for example, 1 of 20 children with measles will develop pneumonia, and fewer than 1 of 1 million children who receive MMR will develop encephalopathy.[42,45] Talk about risks associated with other daily activities to help provide context.[42] Use personal stories -- counter the compelling stories parents can find in the media with compelling anecdotes of your own.[39,40] Know the vaccine -- acknowledge the known side effects, but also emphasize the evidence that supports the safety and benefit of the MMR vaccine. Know about additional resources for parents so that they have ways to get more reliable information.[25,40,44] Know about resources for yourself that provide communication tips, vaccine safety information, and disease information (see Suggested Resources).[25,40,44] Keep talking. If a family continues to decline vaccination despite your efforts, this poses an ethical dilemma between respecting the family's beliefs and your professional obligations and beliefs about what is important for the child's health. The AAP Committee on Bioethics does not recommend discharging a family from one's practice if they refuse or delay vaccination.[40,44] However, guidelines are available for documentation of vaccine refusal, and clinicians can have parents or other guardians to sign a refusal-to-vaccinate waiver. If the relationship with the family cannot be maintained as a result of significant distrust or difficulty with communication, a clinician can then encourage the family to find another provider.[25,44] Summary Despite several years of progress, measles is making a comeback. As long as clusters of unvaccinated individuals persist, outbreaks will continue and potentially grow. It is important that we are prepared to recognize, manage, and prevent this contagious disease. It is even more important that we are prepared to communicate with families about measles and the MMR vaccine in the face of increasing concerns about vaccines. Suggested Resources Vaccines The Children's Hospital of Philadelphia: Vaccine Education Center Vaccine education information for healthcare providers, educators, and parents National Network for Immunization Information Resources for communicating with families AAP: Immunization Resources for parents and healthcare professionals Offit PA, Moser CA. Vaccines and Your Child: Separating Fact From Fiction. New York, NY: Columbia University Press; 2011. CDC: Vaccine Safety Datalink Project Measles CDC: Measles (Rubeola) WHO: Media Centre -- Measles Fact Sheet
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WHO: Media Centre -- Measles Fact Sheet WHO: Immunization, Vaccines and Biologicals Topics -- Measles
References

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23. Edelson PJ, Anderson JA. Reported cases of measles in international air travelers to the United States, August 2005-March 2008. J Travel Med. 2011;18:178-182. Abstract 24. Centers for Disease Control and Prevention (CDC). Measles among U.S.-bound refugees from Malaysia -California, Maryland, North Carolina, and Wisconsin, August-September 2011. MMWR Morb Mortal Wkly Rep. 2011;60:1281-1282. Abstract 25. American Academy of Pediatrics. Measles. Red Book Online. 2009:444-455. http://aapredbook.aappublications.org/cgi/content/extract/2009/1/3.77 Accessed January 7, 2012. 26. World Health Organization. WHO-recommended standards for surveillance of selected vaccine-preventable diseases. Geneva: World Health Organization; 2010. http://whqlibdoc.who.int/hq/2003/WHO_V&B_03.01.pdf Accessed January 7, 2012. 27. CDC: Measles (Rubeola) -- 2010 Case Definition. http://www.cdc.gov/osels/ph_surveillance/nndss/casedef/measles_2010.htm Accessed January 20, 2012. 28. Watson JC, Hadler SC, Dykewicz CA, Reef S, Phillips L. Measles, mumps, and rubella -- vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1998;47:1-57. 29. Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 1998;351:637-641. Abstract 30. Baker JP. Mercury, vaccines, and autism: one controversy, three histories. Am J Public Health. 2008;98:244253. Abstract 31. DeStefano F. Vaccines and autism: evidence does not support a causal association. Clin Pharmacol Ther. 2007;82:756-759. Abstract 32. Farrington CP, Miller E, Taylor B. MMR and autism: further evidence against a causal association. Vaccine. 2001;19:3632-3635. Abstract 33. Fombonne E, Chakrabarti S. No evidence for a new variant of measles-mumps-rubella-induced autism. Pediatrics. 2001;108:E58. 34. Stratton K, Gable A, Shetty P, McCormick M. Immunization Safety Review Committee, Board on Health Promotion and Disease Prevention. Immunization Safety Review: Measles-Mumps-Rubella Vaccine and Autism. Washington, DC, The National Academies Press; 2001. 35. Meadows M. IOM report: no link between vaccines and autism. FDA Consum. 2004;38:18-19. 36. Stratton S, Ford F, Rusch E, Wright Clayton E. Committee to Review Adverse Effects of Vaccines; Institute of Medicine. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press; 2011. 37. Kennedy A, Basket M, Sheedy K. Vaccine attitudes, concerns, and information sources reported by parents of young children: results from the 2009 HealthStyles survey. Pediatrics. 2011;127 Suppl 1:S92-S99. Abstract 38. Walther S. A parent's decision on immunization: making the right choice. Pediatrics. 2011;127 Suppl 1:S5-S8. Abstract 39. Offit PA, Coffin SE. Communicating science to the public: MMR vaccine and autism. Vaccine. 2003;22:1-6. Abstract 40. Healy CM, Pickering LK. How to communicate with vaccine-hesitant parents. Pediatrics. 2011;127 Suppl 1:S127-S133. Abstract 41. Freed GL, Clark SJ, Butchart AT, Singer DC, Davis MM. Sources and perceived credibility of vaccine-safety information for parents. Pediatrics. 2011;127 Suppl 1:S107-S112. Abstract 42. Turnbull AE. Fear, numbers, and measles. Health Commun. 2011;26:775-776. Abstract 43. Macdonald NE, Smith J, Appleton M. Risk perception, risk management and safety assessment: What can governments do to increase public confidence in their vaccine system? Biologicals. 2011 Oct 10. [Epub ahead of print]. 44. Gilmour J, Harrison C, Asadi L, Cohen MH, Vohra S. Childhood immunization: when physicians and parents disagree. Pediatrics. 2011;128 Suppl 4:S167-S174. Abstract 45. Daley MF, Glanz JM. Straight talk about vaccination. Sci Am. 2011;305:32, 34.
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