Vaccine-Preventable Diseases In Pediatric Patients: A Review Of Measles, Mumps, Rubella, And Varicella

Table of Contents

 

1. Abstract
2. Case Presentations
3. Introduction
4. Critical Appraisal of the Literature
5. Etiology And Pathophysiology
   1. Measles
   2. Mumps
   3. Rubella
   4. Varicella
6. Epidemiology
   1. Measles
   2. Mumps
   3. Rubella
   4. Varicella
7. Presenting Clinical Features
   1. Measles
   2. Mumps
   3. Rubella
   4. Varicella
8. Differential Diagnosis
9. Prehospital Care
10. Emergency Department Evaluation
    1. History
    2. Physical Examination
       1. General Examination
       2. Presentations Associated With Vaccine-Preventable Diseases
11. Diagnostic Studies
    1. Reporting Diagnosed Cases
12. Treatment
    1. General Treatment
    2. Disease-Specific Treatment
       1. Measles
       2. Mumps
       3. Rubella
       4. Varicella
    3. Adverse Events Associated With Vaccination
13. Special Circumstances
    1. Patients At High Risk For Severe Disease
    2. Management Of Contact Exposure
14. Time- And Cost-Effective Strategies
15. Controversies And Cutting Edge
16. Disposition
17. Summary
18. Risk Management Pitfalls In Patients With Measles, Mumps, Rubella, And Varicella
19. Case Conclusions
20. Clinical Pathway For Managing Pediatric Patients Presenting With Signs Of Measles, Rubella, And Varicella
21. Tables And Figures
    1. Table 1. Transmission Route, Incubation Period, And isolation Period Of Vaccine-Preventable Diseases
    2. Table 2. Differential Diagnosis Of Fever And Rash
    3. Table 3. Recommended Vaccination Schedule For Measles, Mumps, Rubella, And Varicella
    4. Figure 1. Estimated Numbers Of Deaths Prevented By The Measles Vaccine, 2000-2013
    5. Figure 2. Measles Rash
    6. Figure 3. Swollen Area Under The Jaw And In The Cheeks Of A Child WIth Mumps
    7. Figure 4. Infant With Congenital Rubella Syndrome
    8. Figure 5. Varicella Exanthem
22. References

Abstract

Vaccine-preventable diseases such as measles, mumps, rubella, and varicella continue to plague children and adults worldwide. Although public health programs have helped decrease the prevalence and sequelae of these diseases, outbreaks still occur. To limit the spread of these diseases, emergency clinicians must be able to readily identify the characteristic presentations of the rashes associated with measles, rubella, and varicella, as well as the common presenting features associated with mumps. Diagnostic laboratory studies are not usually necessary, as a complete history and physical examination usually lead to an accurate diagnosis. Treatment for these vaccine-preventable diseases usually consists of supportive care, but, in some cases, severe complications and death may occur. This issue provides a review of the clinical features, differential diagnoses, potential complications, and treatment options for measles, mumps, rubella, and varicella.

Case Presentations

A mother reports that her 3-month-old son is fussy and has had a runny nose and fever for the past 5 days. She also notes that the infant developed a red, raised rash initially on his face, which spread to his abdomen and extremities over the course of a day. The mother reports that her son is eating less and has been breathing rapidly. The boy was born full-term in the United States and has no past medical history. He has had 1 vaccination at his primary care physician, at 2 months of age. The family just returned from a trip to London a week ago, and there are no other sick contacts in the family. The infant’s vital signs are: heart rate, 175 beats/min; respiratory rate, 45 breaths/min; rectal temperature, 38.3^oC (101^oF); and oxygen saturation, 91% on room air. The physical examination findings demonstrate bilateral conjunctival injection with no purulent drainage, rhinorrhea, and slightly dry lips and oral mucosa. The infant has a blanching maculopapular exanthem to his face, trunk, extremities, palms, and soles. Upon auscultation, he has rales at both lung bases.

A 6-month-old girl, who was born full-term, is brought into the ED by her mother. The mother states that her daughter has had a fever and a rash for 3 days; the rash began on the infant’s face as “water blisters." The mother also states that her daughter has not felt well for the last 2 days, has had decreased urine output, decreased activity, and has been irritable. According to the mother, the girl is up to date with recommended vaccinations for her age. There are no sick contacts in the family; however, the patient’s grandmother has a painful rash on her back. The infant’s vital signs are: heart rate, 170 beats/ min; respiratory rate, 25 breaths/min; rectal temperature, 38.5^oC (101.4^oF); and oxygen saturation, 98% on room air. The physical examination is significant for vesicles on an erythematous base on the girl’s face, trunk, extremities, and back, as well as many excoriated and scabbed lesions. There are erythematous papules on the anterior buccal mucosa and the posterior pharynx. The infant’s mucous membranes are dry, her lungs are clear, and her skin is warm. The infant is crying and her mother is having difficulty consoling her.

What is the etiology for these patients’ fever and rash? What are the possible complications of their illnesses? Do these patients need any diagnostic testing or specialty consultation? Should these patients be isolated in the ED? What treatments are indicated? Should these patients be admitted? Should their contacts be isolated or treated?

Introduction

Vaccine-preventable diseases such as measles, mumps, rubella, and varicella continue to afflict children in the United States and abroad. The estimate of global vaccine coverage is approximately 84% for these 4 diseases. As of 2014, 29% of the World Health Organization (WHO) member states (57 countries) administer the measles vaccine. In 2013, approximately 21.5 million children did not receive the first dose of the measles vaccine, and 60% of these children were from 6 countries—India, Nigeria, Pakistan, Ethiopia, Indonesia, and the Democratic Republic of the Congo.¹ Even in industrialized countries with national vaccination guidelines (eg, the United States), vaccination coverage for measles, mumps, rubella, and varicella in school-aged children is not complete.² Vaccine failures, waning immunity, vaccine rejection, and public fear have led to community outbreaks and clinical sequelae in those exposed and affected. This issue of Pediatric Emergency Medicine Practice will summarize these 4 formerly common childhood diseases that can be prevented with vaccination, but may still sporadically occur. This information will enable emergency clinicians to effectively recognize children with these diseases to ensure appropriate treatment and decrease their spread.

Critical Appraisal Of The Literature

A literature search was performed in PubMed, using the search terms measles, mumps, rubella, varicella, vaccine-preventable, and disease outbreaks. The Cochrane Database of Systematic Reviews was searched using the terms measles, mumps, rubella, varicella, and vitamin A. The United States Centers for Disease Control and Prevention (CDC) and the WHO websites were searched for relevant materials, including recent epidemiological data. Most data about these diseases are from case series and epidemiological reports.

Risk Management Pitfalls In Patients With Measles, Mumps, Rubella, And Varicella

1. “The whole waiting room was coughing and sneezing. I didn’t think to isolate this child.“
   Patients with measles, mumps, rubella, or varicella should be isolated, since their respiratory droplets and secretions can be spread to other patients, hospital staff, and family members. Patients infected with measles need airborne precautions for 4 days after they develop a rash. All heathcare personnel should follow respiratory control precautions when treating a patient with measles. Exposed staff or family members should be offered post-exposure prophylaxis if they cannot provide evidence of immunity against measles.
    
2. “The adolescent patient with varicella had her newborn and her grandmother with her while in the ED. Since the patient did not need to be hospitalized, I went ahead and discharged her so they could all go home.”
   Family members who are at risk for vaccine-preventable diseases should be vaccinated as soon as possible within 5 days after exposure to the rash, in hopes of averting or modifying the disease currently or in future exposures. Susceptible varicella contacts should be offered varicella zoster immunoglobulin within 10 days of exposure if they are unable to receive the vaccine.⁷⁰ Susceptible contacts with measles exposure should also be offered intramuscular immunoglobulin or postexposure prophylaxis within 72 hours.³³ There is no role for postexposure prophylaxis for mumps or rubella.
    
3. “I just vaccinated my patient, but I realized I forgot to ask if she may be pregnant.”
   With mumps and measles viruses, the risk to a fetus is only theoretical. Rubella and varicella vaccination during pregnancy harbors a small, but real, risk for developing CRS (1.2%) and congenital varicella infection. Routine termination of pregnancy is not recommended, but counseling about possible risks of infections should be given.^6,70 Vaccinations should be up to date in women of child-bearing age and their sexual partners.
    
4. “I assumed the newborn patient with a rash contracted it from a contact. I didn’t think to ask the mother if she had varicella near the time of delivery.”
   Newborn infants exposed to varicella whose mothers do not have evidence of immunity or whose mothers develop varicella 5 days before or 2 days after delivery are at risk for severe disease, which can lead to death. These infants require varicella immunoglobulin.^52,53,71
    
5. “The patient with mumps did not require hospitalization, so I discharged her without follow-up.”
   Hospital infection control and local and state Departments of Health need to be notified in order to track and notify potential contacts of communicable disease for containment of the spread of measles, mumps, rubella, and varicella.
    
6. “I didn’t want the patient with measles to develop an ear infection, so I prescribed him antibiotics.”
   Antibiotics are not recommended to prevent the bacterial complications of measles, such as pneumonia and otitis media. Antibiotics are indicated for the treatment of overt infection, but more evidence from high-quality randomized controlled trials is needed to recommend the types of antibiotics, the duration of treatment, and the day of initiation.⁷² While administration of antibiotics is not recommended, 2 doses of vitamin A is recommended to prevent ocular complications in patients with measles.
    
7. “I didn’t think to ask if any of the family members of the patient with rubella may be pregnant.”
   Congenital rubella infection occurs with maternal infection during the first 20 weeks of pregnancy. Infection may cause miscarriage, stillbirth, and low birth weight.³⁷ Rubella infection may be mild and may not be evident unless titers are performed. A pregnant woman should be informed of the exposure and potential harm it may cause the fetus. Close follow-up with obstetrics is vital.
    
8. “The patient was fully vaccinated, so I did not think he could have measles.”
   Vaccination does not provide absolute coverage against disease. The MMR vaccine is about 95% effective in preventing measles and 88% effective in preventing mumps after 2 doses.⁶⁷
    
9. “I wanted to discharge the patient with varicella as quickly as possible to limit the chance of spreading the disease, so I discharged him home even though he wouldn’t drink anything in the ED.”
   Dehydration is a complication of any childhood disease, especially in patients who have signs of poor oral intake, decreased urine output, and other fluid losses such as vomiting or diarrhea. Physical examination should include evaluation of mucous membranes, heart rate, capillary refill, palpation of peripheral pulses, and the presence of tears. Patients with dehydration should be hospitalized with isolation precautions.
    
10. “The only travel our patient had was to Europe. I didn’t think these diseases could be contracted there.”
    Patients may be at risk for vaccine-preventable diseases throughout the world. Developed countries such as those of Eastern Europe, the United Kingdom, France, and Japan may be sources for infection. A thorough travel history is important when evaluating for a potential communicable disease. This information may be cross-referenced with outbreak information from the WHO and CDC.

Tables and Figures

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. The most informative references cited in this paper, as determined by the authors, are noted by an asterisk (*) next to the number of the reference.

1. Centers for Disease Control and Prevention. Measles and rubella move fast. Measles & Rubella Initiative: a global partnership to stop measles & rubella. Available at: http://www.cdc.gov/globalhealth/measles/pdf/measles-factsheet2015.pdf. Accessed November 14, 2016. (Expert review)
2. Seither R, Masalovich S, Knighton C, et al. Vaccination coverage among children in kindergarten — United States, 2013–14 school year. MMWR Morb Mortal Wkly Rep. 2014;63(41):913-920. (Prospective database report)
3. de Vries RD, Mesman AW, Geijtenbeek TB, et al. The pathogenesis of measles. Curr Opin Virol. 2012;2(3):248-255. (Review)
4. Naim HY. Measles virus. Hum Vaccin Immunother. 2015;11(1):21-26. (Review)
5. Vareil MO, Rouibi G, Kassab S, et al. Epidemic of complicated mumps in previously vaccinated young adults in the South-West of France. Med Mal Infect. 2014;44(11-12):502-508. (Retrospective case series; 7 patients)
6. Centers for Disease Control and Prevention. Rubella. Epidemiology and prevention of vaccine-preventable diseases. Available at: http://www.cdc.gov/vaccines/pubs/pinkbook/rubella.html. Accessed November 14, 2016. (Review)
7. Banatvala JE, Brown DW. Rubella. Lancet. 2004;363(9415):1127-1137. (Review)
8. World Health Organization. Varicella and herpes zoster vaccines: WHO position paper, June 2014. Wkly Epidemiol Rec. 2014;89(25):265-287. (Position paper)
9. Centers for Disease Control and Prevention. A new product (VariZIG) for postexposure prophylaxis of varicella available under an investigational new drug application expanded access protocol. MMWR Morb Mortal Wkly Rep. 2006;55(8):209- 210. (Fact sheet)
10. World Heath Organization. Measles. Available at: http://www.who.int/mediacentre/factsheets/fs286/en/. Accessed November 14, 2016. (Fact sheet)
11. Katz SL, Hinman AR. Summary and conclusions: measles elimination meeting, 16-17 March 2000. J Infect Dis. 2004;189 Suppl 1:S43-S47. (Review)
12. Elam-Evans LD, Yankey D, Singleton JA, et al. National, state, and selected local area vaccination coverage among children aged 19-35 months - United States, 2013. MMWR Morb Mortal Wkly Rep. 2014;63(34):741-748. (National surveillance data)
13. National Vaccine Information Center. Vaccine laws. Available at: http://www.nvic.org/vaccine-laws.aspx. Accessed November 14, 2016. (Fact sheet)
14. Whitaker JA, Poland GA. Measles and mumps outbreaks in the United States: think globally, vaccinate locally. Vaccine. 2014;32(37):4703-4704. (Editorial)
15. Macartney K. Prevention of varicella: time for two-dose vaccination. Lancet. 2014;383(9925):1276-1277. (Editorial comment)
16. Centers for Disease Control and Prevention. Measles - United States, 2011. MMWR Morb Mortal Wkly Rep. 2012;61(15):253-257. (Surveillance data)
17. Gastanaduy PA, Redd SB, Fiebelkorn AP, et al. Measles - United States, January 1-May 23, 2014. MMWR Morb Mortal Wkly Rep. 2014;63(22):496-499. (Prospective case series)
18. Clemmons NS, Gastanaduy PA, Fiebelkorn AP, et al. Measles - United States, January 4-April 2, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(14):373-376. (Prospective case series)
19. World Health Organization. Global measles and rubella strategic plan: 2012-2020. Available at: http://www.measlesrubellainitiative.org/wp-content/uploads/2013/06/Measles-Rubella-Strategic-Plan.pdf. Accessed November 14, 2016. (Strategic plan)
20. Centers for Disease Control and Prevention. Mumps cases and outbreaks. Available at: http://www.cdc.gov/mumps/outbreaks.html. Accessed November 14, 2016. (Prospective case series)
21. Klein J. Mumps outbreak prompts NHL teams to take precautions. Available at: http://www.nytimes.com/2014/12/07/sports/hockey/mumps-outbreak-prompts-nhl-teams-to-take-precautions.html?_r=0. Accessed November 14, 2016. (News report)
22. Hviid A, Rubin S, Muhlemann K. Mumps. Lancet. 2008;371(9616):932-944. (Review)
23. * Papania MJ, Wallace GS, Rota PA, et al. Elimination of endemic measles, rubella, and congenital rubella syndrome from the Western hemisphere: the US experience. JAMA Pediatr. 2014;168(2):148-155. (Expert review)
24. Centers for Disease Control and Prevention. Nationwide rubella epidemic--Japan, 2013. MMWR Morb Mortal Wkly Rep. 2013;62(23):457-462. (Prospective case series)
25. Centers for Disease Control and Prevention. Rubella and congenital rubella syndrome control and elimination - global progress, 2000-2012. MMWR Morb Mortal Wkly Rep. 2013;62(48):983-986. (Worldwide surveillance data)
26. * Marin M, Meissner HC, Seward JF. Varicella prevention in the United States: a review of successes and challenges. Pediatrics. 2008;122(3):e744-e751. (Review)
27. Centers for Disease Control and Prevention. Evolution of varicella surveillance--selected states, 2000-2010. MMWR Morb Mortal Wkly Rep. 2012;61(32):609-612. (Surveillance data)
28. European Centre for Disease Prevention and Control. Varicella vaccination in the European Union. Stockholm, Sweden: ECDC Guidance: January 2015. Available at: http:// ecdc.europa.eu/en/publications/Publications/Varicella- Guidance-2015.pdf. Accesssed November 14, 2016. (Review)
29. Tannous LK, Barlow G, Metcalfe NH. A short clinical review of vaccination against measles. JRSM Open. 2014;5(4):2054270414523408. (Review)
30. Centers for Disease Control and Prevention. Measles. Epidemiology and prevention of vaccine-preventable diseases. Available at: http://www.cdc.gov/vaccines/pubs/pinkbook/meas.html. Accessed November 14, 2016. (Review)
31. Griffin DE. Measles virus-induced suppression of immune responses. Immunol Rev. 2010;236:176-189. (Review)
32. Gahr P, DeVries AS, Wallace G, et al. An outbreak of measles in an undervaccinated community. Pediatrics. 2014;134(1):e220-e228. (Prospective case series; 21 patients)
33. Centers for Disease Control and Prevention. Measles (rubeola). Available at: http://www.cdc.gov/measles/hcp/index.html. Accessed November 14, 2016. (Review)
34. American Academy of Pediatrics. Mumps. In: Pickering L, Baker C, Kimberlin D, et al, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:468-472. (National recommendations)
35. Centers for Disease Control and Prevention. Updated recommendations for isolation of persons with mumps. MMWR Morb Mortal Wkly Rep. 2008;57(40):1103-1105. (Review)
36. Davis NF, McGuire BB, Mahon JA, et al. The increasing incidence of mumps orchitis: a comprehensive review. BJU Int. 2010;105(8):1060-1065. (Review)
37. * Thompson KM, Simons EA, Badizadegan K, et al. Characterization of the risks of adverse outcomes following rubella infection in pregnancy. Risk Anal. 2016;36(7):1315-1331. (Systematic review)
38. Centers for Disease Control and Prevention. Varicella. Epidemiology and prevention of vaccine-preventable diseases. Available at: http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/varicella.pdf. Accessed November 14, 2016. (Review)
39. Speer M. Varicella-zoster infection in the newborn. UpToDate. Available at: http://www.uptodate.com/contents/varicella-zoster-infection-in-the-newborn. Accessed November 14, 2016. (Review)
40. Ziebold C, von Kries R, Lang R, et al. Severe complications of varicella in previously healthy children in Germany: a 1-year survey. Pediatrics. 2001;108(5):E79. (Surveillance study)
41. Science M, MacGregor D, Richardson SE, et al. Central nervous system complications of varicella-zoster virus. J Pediatr. 2014;165(4):779-785. (Prospective case series; 84 patients)
42. Baszis K, Toib D, Cooper M, et al. Recurrent parotitis as a presentation of primary pediatric SjÖgren syndrome. Pediatrics. 2012;129(1):e179-e182. (Cases series; 4 patients)
43. * Centers for Disease Control and Prevention. Control and prevention of rubella: evaluation and management of suspected outbreaks, rubella in pregnant women, and surveillance for congenital rubella syndrome. MMWR Recomm Rep. 2001;50(Rr-12):1-23. (National recommendations)
44. Centers for Disease Control and Prevention. Interpreting laboratory tests. Chickenpox (varicella). Available at: http://www.cdc.gov/chickenpox/hcp/lab-tests.html. Accessed November 14, 2016. (Review)
45. Oranje AP, Folkers E. The Tzanck smear: old, but still of inestimable value. Pediatr Dermatol. 1988;5(2):127-129. (Review)
46. West CE. Vitamin A and measles. Nutr Rev. 2000;58:S46-S54. (Review)
47. * Imdad A, Herzer K, Mayo-Wilson E, et al. Vitamin A supplementation for preventing morbidity and mortality in children from 6 months to 5 years of age. Cochrane Database Syst Rev. 2010(12):CD008524. (Systematic review)
48. World Health Organization. Vitamin A supplements: a guide to the treatment and prevention of vitamin A deficiency and xerophthalmia. Second edition. Geneva: WHO, 1997.(Guidelines)
49. Young MK, Nimmo GR, Cripps AW, et al. Post-exposure passive immunisation for preventing measles. Cochrane Database Syst Rev. 2014(4):CD010056. (Systematic review)
50. Yapanoglu T, Kocaturk H, Aksoy Y, et al. Long-term efficacy and safety of interferon-alpha-2B in patients with mumps orchitis. Int Urol Nephrol. 2010;42(4):867-871. (Prospective interventional study; 37 patients)
51. Fiebelkorn AP, Lawler J, Curns AT, et al. Mumps postexposure prophylaxis with a third dose of measles-mumps-rubella vaccine, Orange County, New York, USA. Emerg Infect Dis. 2013;19(9):1411-1417. (Prospective case control; 239 patients)
52. * Centers for Disease Control and Prevention. Updated recommendations for use of VariZIG--United States, 2013. MMWR Morb Mortal Wkly Rep. 2013;62(28):574-576. (Expert review)
53. Bapat P, Koren G. The role of VariZIG in pregnancy. Expert Rev Vaccines. 2013;12(11):1243-1248. (Review)
54. Centers for Disease Control and Prevention. Recommended immunization schedules for persons aged 0 through 18 years, United States, 2015. Available at: http://www.cdc.gov/vaccines/schedules/downloads/child/0-18yrs-child-combined-schedule.pdf. Accessed November 14, 2016. (Review)
55. Centers for Disease Control and Prevention. Mumps. Epidemiology and prevention of vaccine-preventable diseases. Available at: http://www.cdc.gov/vaccines/pubs/pinkbook/mumps.html. Accessed November 14, 2016. (Review)
56. Maglione MA, Das L, Raaen L, et al. Safety of vaccines used for routine immunization of US children: a systematic review. Pediatrics. 2014;134(2):1-13. (Systematic review)
57. O’Leary ST, Glanz JM, McClure DL, et al. The risk of immune thrombocytopenic purpura after vaccination in children and adolescents. Pediatrics. 2012;129(2):248-255. (Retrospective case series; 197 patients)
58. Marin M, Broder KR, Temte JL, et al. Use of combination measles, mumps, rubella, and varicella vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010;59(Rr-3):1-12. (Expert review)
59. Centers for Disease Control and Prevention. Thimerosal in vaccines. Vaccine safety 2015. Available at; http://www. cdc.gov/vaccinesafety/Concerns/thimerosal/. Accessed November 14, 2016. (Expert review)
60. Institute of Medicine of the National Academies. Varicella virus vaccine. In: Stratton K, Ford A, Rusch E, et al, eds. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press; 2011:239-292. (IOM review)
61. * Black S, Shinefield H, Ray P, et al. Postmarketing evaluation of the safety and effectiveness of varicella vaccine. Pediatr Infect Dis J. 1999;18(12):1041-1046. (Retrospective case control; 89,753 patients)
62. Liese JG, Grote V, Rosenfeld E, et al. The burden of varicella complications before the introduction of routine varicella vaccination in Germany. Pediatr Infect Dis J. 2008;27(2):119- 124. (Prospective nationwide surveillance; 918 patients)
63. Cohen A, Moschopoulos P, Stiehm RE, et al. Congenital varicella syndrome: the evidence for secondary prevention with varicella-zoster immune globulin. CMAJ. 2011;183(2):204- 208. (Systematic review)
64. American Academy of Pediatrics. Measles. In: Pickering L, Baker C, Kimberlin D, et al, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:444-455. (National recommendations)
65. American Academy of Pediatrics. Rubella. In: Pickering L, Baker C, Kimberlin D, et al, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:579-584. (Guidelines)
66. Uno Y, Uchiyama T, Kurosawa M, et al. The combined measles, mumps, and rubella vaccines and the total number of vaccines are not associated with development of autism spectrum disorder: the first case-control study in Asia. Vaccine. 2012;30(28):4292-4298. (Prospective case-control study; 189 patients)
67. * Demicheli V, Rivetti A, Debalini MG, et al. Vaccines for measles, mumps and rubella in children. Cochrane Database Syst Rev. 2012(2):CD004407. (Systematic review)
68. DeStefano F, Price CS, Weintraub ES. Increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines is not associated with risk of autism. J Pediatr. 2013;163(2):561-567. (Retrospective case-control study; 256 children, 752 controls)
69. Jain A, Marshall J, Buikema A, et al. Autism occurrence by MMR vaccine status among US children with older siblings with and without autism. JAMA. 2015;313(15):1534-1540. (Retrospective cohort study; 95,727 children)
70. * Marin M, Guris D, Chaves SS, et al. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56(Rr-4):1-40. (National recommendations)
71. Centers for Disease Control and Prevention. Managing people at risk for severe varicella. Chickenpox (varicella). Available at: http://www.cdc.gov/chickenpox/hcp/persons-risk.html. Accessed November 14, 2016. (Expert review)
72. Kabra SK, Lodha R. Antibiotics for preventing complications in children with measles. Cochrane Database Syst Rev. 2013(8):CD001477. (Systematic review)