Measles is an acute, highly contagious disease that results from infection with the measles virus and is an important cause of morbidity and mortality worldwide.1 Measles was declared eliminated (the absence of endemic virus transmission in a defined geographical area, such as a country or region, for more than 12 months) in the United States in 2000. However, outbreaks continue to occur in the United States, largely in unvaccinated people. According to the Centers for Disease Control and Prevention, in 2019, there were more than 1200 measles cases in 31 states, representing the most cases seen in the United States in more than 25 years.2
Measles is a paramyxovirus transmitted between humans that attacks epithelial structures (eg, eyes, oropharynx, lungs, and intestines), with the respiratory tract rarely escaping impact. A characteristic rash typically appears 14 days after exposure, generally 2 to 3 days after fever and upper respiratory symptoms begin. The infection can result in severe, sometimes permanent, complications including pneumonia, seizures, brain damage, and even death.1
Measles is the most contagious infectious disease currently known to humans. Ninety percent of susceptible people exposed to the virus become infected, unless they are immune. A measles, mumps, and rubella (MMR) vaccine, given in a 2-dose series, one at 12 to 15 months and another at 4 to 6 years, is the best prevention against measles. Protection of vulnerable individuals who have been exposed to the virus is achieved by giving measles vaccine within 72 hours of exposure, or intramuscular or intravenous immunoglobulin up to day 6 after exposure, to prevent disease. Treatment for individuals with measles is typically supportive in nature, including acetaminophen or ibuprofen and intravenous fluids. Additional interventions, such as antibiotics, may be indicated for measles-related complications.1 There is currently no antiviral medication available specifically for measles treatment.
The management of patients with measles also includes provision of vitamin A for reducing complications and mortality. Vitamin A deficiency affects the severity of measles; delays recovery; can lead to measles-related complications, including blindness; and is associated with a higher rate of deaths.3–5 Vitamin A has been recommended for decades by the American Academy of Pediatrics (AAP) and the World Health Organization (WHO) for hospitalized children with measles.6,7 However, recent studies show that vitamin A has not been used appropriately to treat US children with measles—either by not using vitamin A at all or by using insufficiently low doses.8 The reason for this is unknown.
With an increased number of measles cases in the United States, existing international guidelines in place, and the known benefits of vitamin A well documented, why is there low adherence to these recommendations? It is timely and relevant to refresh the evidence on this topic and urgently disseminate knowledge of this important infectious disease intervention to practicing healthcare professionals in the United States.
In November 2019, the National Foundation for Infectious Diseases (NFID) convened a summit that included multidisciplinary subject matter experts from across the United States representing pediatric infectious diseases, ophthalmology, infection prevention and control, pediatric hospital medicine, public health, healthcare epidemiology, nursing, pharmacy, infectious disease researchers, and those involved in the most recent US measles outbreaks, to discuss the use of vitamin A in US measles management and, specifically, published literature and gaps, current understanding of the physiologic role and immune impact of vitamin A, current recommendations and adherence, key research challenges and needs in the United States, and how to best optimize language and practices to help provide clarity to US healthcare professionals and the public. This article outlines key discussion points and recommendations from the Summit discussions.
THE ROLE OF VITAMIN A IN MEASLES INFECTION
Vitamin A, or retinol, is a micronutrient that is critical in supporting the immune system, vision, reproduction, and cellular communication. It is known as an anti-infective vitamin because of its role in enhancing immune function including immunoglobulin expression and cellular immune response. Diet is the primary source of vitamin A from foods such as milk, eggs, cheese, fortified cereals, leafy green vegetables, orange vegetables, fish, and meat (in particular, liver). Less commonly ingested, but high in vitamin A, is cod liver oil. The recommended daily allowance for vitamin A depends on your age and sex. Average daily recommended amounts are listed in micrograms (μg) of retinol activity equivalent (RAE). Recommendations are 900 and 700 μg RAE per day for men and women, respectively. For pregnant and breastfeeding women, the recommendations are higher. For children younger than 13 years, the recommendations fall within the range of 300 to 600 μg RAE dependent upon age. Individuals can get the recommended amounts through a balanced diet.9
Vitamin A deficiency in the United States is rare.10 It is much more common in low- and middle-income countries because individuals often have limited access to foods containing vitamin A from animal-based food sources and/or do not commonly consume fresh fruits and vegetables.9
Because of the important role vitamin A plays in immune function, vitamin A deficiency affects the severity of illness and the rates of deaths associated with measles. Studies in low- and middle-income countries have found vitamin A deficiency to be associated with severe measles-related complications and death in children, thus delaying recovery and promoting xerophthalmia. Xerophthalmia is the term used to describe the ocular manifestations of vitamin A deficiency including night blindness, severe conjunctival dryness, and Bitot spots (white keratins build up on the conjunctiva and are characteristically seen in vitamin A deficiency). In worst-case scenarios, corneal ulceration can develop and lead to blindness.3–5,11
In the United States, studies have shown that hospitalized measles patients are frequently vitamin A deficient, with low serum vitamin A levels correlating with the severity of measles disease.12–14 One study among US children with measles showed that children with no known previous vitamin A deficiency exhibited a significant decline in their serum retinol levels during the acute phase of measles. This decline in circulating retinol was associated with an increased duration of fever, higher hospitalization rates, and decreased antibody titers. In the study, plasma retinol levels returned to normal during the recovery phase.14
In the past 2 decades, research has helped explain the mechanisms involved in the interaction between measles infection and vitamin A deficiency.
However, measuring retinol levels during infection is time consuming, and tests can be costly. In addition, there is a need for clarity on what test to use and how test results should impact clinical care. The need for additional research remains, as the mechanisms by which vitamin A affects immune function have not been completely examined at the molecular level but vitamin A is inexpensive and, if needed, acts quickly.
HISTORY OF VITAMIN A FOR MEASLES MANAGEMENT GLOBALLY
In 1932 in London, England, Joseph B. Ellison,15 MD, and colleagues were the first to suggest that vitamins A and D may have a protective effect during measles infection by limiting the severity of pulmonary complications. Since then, studies have shown reductions in morbidity and mortality in children with measles treated with vitamin A in low- and middle-income countries.3,16,17
In contrast, recognition of vitamin A deficiency increased in the 1980s after research published in The Lancet from Alfred Sommer and colleagues18 that found vitamin A deficiency dramatically increased mortality. The study showed that the mortality rate among Indonesian children with mild xerophthalmia was, on average, 4 times the rate and, in some age groups, 8 to 12 times the rate, compared with children without xerophthalmia.
To demonstrate the link between even mild vitamin A deficiency and pediatric mortality, Sommer and colleagues16 conducted large-scale, community-based, randomized trials from 1983 through 1992. The first large-scale randomized field trial of the impact of 200,000 international units (IU) of vitamin A supplementation every 6 months on subsequent child mortality in Aceh, Indonesia, was published in 1986. The results showed a 34% reduction in mortality among children aged 1 to 5 years. These results were replicated in subsequent trials in Africa and Asia.
After this study, questions were posed: was vitamin A deficiency responsible in part for the large number of measles deaths observed in children, and would management with vitamin A reduce measles case fatality? Follow-up studies in several African countries showed that vitamin A in children with measles could reduce fatality by roughly 50%, as Ellison had also observed.3,17
RECOMMENDATIONS AND GUIDELINES FOR VITAMIN A IN MEASLES MANAGEMENT—GLOBAL AND UNITED STATES
Soon after many of the vitamin A trials were published, the WHO and the United Nations Children's Fund issued a joint statement recommending that vitamin A be administered to all children given a diagnosis of measles in communities where vitamin A deficiency (serum retinol < 10 μg/dL) is a recognized problem and where mortality related to measles is 1% or greater.6
In contrast, vitamin A deficiency is not recognized as a widespread or significant problem in high-income economies. As such, vitamin A levels of children with measles have not been extensively studied in the United States.
Still, in looking at the WHO/United Nations Children's Fund joint statement, there remained a desire to explore whether US children with measles would benefit from vitamin A, although the United States did not meet these specific criteria.
In 1993, the AAP Committee on Infectious Diseases met to review the literature associated with vitamin A and measles in low- and middle-income nations. Although the Committee recognized that the available data were incomplete and insufficient to determine the appropriate use of vitamin A for all children with measles, they did recommend that vitamin A supplementation be considered in select circumstances for US children with measles. At that time, the AAP advised about the limited data on efficacy and safety of vitamin A in US children and cautioned practitioners to select patients carefully and monitor clinically for adverse effects (eg, bulging fontanel, headache, and vomiting).19
The AAP Committee revisited that language in 2018, recognizing that even in countries where measles is not usually severe, vitamin A should be given to all children with severe measles,7 because
- ▪ the WHO recommends it for all children with acute measles, regardless of their country of residence7;
- ▪ children in the United States can have low serum vitamin A concentrations12–14;
- ▪ low vitamin A concentrations correlate with more severe measles disease3–5;
- ▪ the measles virus can deplete vitamin A stores3,4; and
- ▪ in low- and middle-income countries, vitamin A is associated with decreased mortality and morbidity.3–5
The AAP Red Book (report of the Committee on Infectious Diseases) states the WHO recommendation but does not tailor it further for the US population.
Red Book: Report of the Committee on Infectious Diseases
American Academy of Pediatrics 2018–2021. 31st Edition
Vitamin A. Vitamin A treatment for children with measles in resource-limited countries has been associated with decreased morbidity and mortality rates. Low serum concentrations of vitamin A also have been found in children in the United States, and children with more severe measles illness have lower vitamin A concentrations.
The WHO currently recommends vitamin A for all children with acute measles regardless of their country of residence. Vitamin A for treatment of measles is administered once daily for 2 days, at the following doses:
- ▪ 200,000 IU for children 12 months or older;
- ▪ 100,000 IU for infants 6 through 11 months old; and
- ▪ 50,000 IU for infants younger than 6 months.
An additional (eg, a third) age-specific dose should be given 2 through 4 weeks later to children with clinical signs and symptoms of vitamin A deficiency.
Even in countries where measles is not usually severe, vitamin A should be given to all children with severe measles (eg, requiring hospitalization). Parenteral and oral formulations of vitamin A are available in the United States.
WHERE WE ARE TODAY: VITAMIN A AND MEASLES MANAGEMENT IN THE UNITED STATES
Adherence to Guidelines
For the past 2 decades, regardless of the recommendations from AAP, WHO, and others, there has been limited use of vitamin A for measles management in the United States. A retrospective, descriptive study from Hester et al8 looked at patients aged 0 to 18 years admitted between January 2004 and December 2018 to a hospital contributing data to the Pediatric Health Information Systems. In that study, 52 US children's hospitals reported, on average, 12 years of data to the Pediatric Health Information Systems, and 34 hospitals reported at least 1 measles-related admission (median of 3 admissions per hospital). Of these, only 39% reported using vitamin A to help manage measles infection.
In addition, in hospitals that did administer vitamin A, most children were not receiving the age-based high dose recommended by the WHO and AAP. The majority received 10,000 IU versus the recommended 50,000 to 200,000 IU (see Table 1).8 This is currently the only known study in the United States evaluating the use of vitamin A in managing measles infection.
VITAMIN A PROPHYLAXIS VS MMR VACCINATION
In addition to low adherence to published guidelines among US healthcare professionals, it has been reported that some parents are using vitamin A prophylactically despite the lack of evidence to suggest a role in preventing measles. Vaccination remains the only proven preventive measure.
In the 2019 measles outbreak in the United States, most cases occurred in Orthodox Jewish communities in New York City and the New York suburb of Rockland County. In both of these areas, a minority of community members who were skeptical about vaccines have been opting out of vaccination for their children, driving vaccine rates down, and allowing the highly contagious virus to spread.
Regarding the use of vitamin A, some members of the Orthodox Jewish community began to rely on recommendations from families who gave their children a spoonful of cod liver oil daily, which contains vitamin A, irrespective of measles exposure and as an alternative to MMR vaccination. Other members of the community began circulating their own guidance on dosage of vitamin A maintaining that “people who took vitamin A got the measles much later” than those who did not.20 It should be noted that vitamin A does not prevent measles. It is not appropriate for parents to use vitamin A as a preventive measure.
In addition, a 2019 outbreak of measles in the island nation of Samoa that has caused more than 82 deaths21 has drastically increased social media commentary regarding vitamin use in measles prevention and management. Comments on social media have suggested the use of vitamin A, vitamin C, or selenium to prevent measles. Further education aimed at the general public is required to help distinguish effective versus ineffective measures in measles management.
A key goal of the Summit was to better understand underlying challenges related to vitamin A guideline adherence and research gaps that would, in turn, help provide clarity to US healthcare professionals and the public. From the diverse challenges reported, several common issues emerged.
Issue: Lack of Current US-Specific Data Verifying Effectiveness of Vitamin A for Measles Management
Although the impact of vitamin A on morbidity and mortality rates has been well documented in low- and middle-income countries, far less is known about the efficacy of vitamin A supplementation in countries with a low measles mortality rate and a population at a lower risk for vitamin A deficiency. The children in the studies by Sommer, Hussey, and Klein were substantially different in growth parameters from the average child in the United States. In addition, the current evidence mostly supports the use of vitamin A supplementation in children younger than 2 years.7,16–18 This may lead to confusion regarding recommendations for supplementation in resource-limited versus well-resourced countries and for young children only or for all children with measles.
Another item that warrants clarification is correlation of vitamin A levels during measles infection. If vitamin A stores are depleted at the time of measles infection, does that warrant use independent of underlying nutritional status? Summit participants discussed baseline vitamin A levels, with differing views on the importance of determining baseline levels before treating with vitamin A.
More clarity in this area is warranted. Specifically, is there a value in measuring vitamin A levels in measles patients upon admission and before supplementation? Is it feasible to get test results back in a timely fashion that are meaningful enough to even consider drawing retinol levels?
Issue: Confusion Around Recommendations From the WHO and AAP
Fortunately, in the United States, most healthcare professionals have never encountered a case of measles. Limited experience with the disease, therefore, may lead to lack of familiarity with the guidelines.
Additional reasons for the low adherence to published recommendations may include guidance that seems contradictory, not applicable to US children, and/or that leaves too much room for interpretation. Specifically, Summit participants noted the following:
- ▪ The published recommendations are all worded slightly differently.6,7
- ▪ The language leaves too much room for interpretation, especially regarding hospitalization. The question was posed: Is vitamin A only for children in the intensive care unit, for all hospitalized children, or for all children including outpatients? The distinction is unclear.
- ▪ Recommendations focus on the benefits of vitamin A in resource-limited countries. With such a focus, the rationale may not be clear for US healthcare professionals who rarely treat measles and are often dealing with better-nourished children.
- ▪ Recommendations do not consider different age ranges, patient populations, or regions. The most severe cases of measles in California, one of the recent outbreak sites, have been in adults, but the current guidelines only address children.
Issue: Confusion Around Dosing With New Unit of Measure
A Cochrane review of 8 randomized controlled trials of treatment with vitamin A for children with measles found that 200,000 IU of vitamin A on 2 consecutive days reduced mortality from measles in children younger than 2 years.22 Research from Hester et al8 shows that most children treated in the United States are not receiving a high enough dosage of vitamin A—only 10,000 IU versus the recommended 100,000 to 200,000 IU.9
In addition, vitamin A is listed on many food and supplement labels in international units, although nutrition scientists rarely use this measure, favoring RAE (see Table 2). Under new US Food and Drug Administration regulations, which went into effect on January 1, 2020, vitamin A is now listed on food and dietary supplement product labels only in micrograms of RAE and not international units, which may further add to healthcare professional confusion.9
Issue: Challenges With Access and Administration of Vitamin A
In addition to confusion around dosing, there may also be challenges in dispensing vitamin A, which is not prescribed often and has a 2-year shelf life. Many hospital pharmacies either do not carry vitamin A or may only stock 1 formulation. The stocked vitamin A certainly will not be in the therapeutic high doses recommended in the guidelines. If pharmacies do not have vitamin A, it will need to be special ordered. Placing special orders may negatively impact time to treatment, and it is unclear that the formulation that healthcare professionals specify (eg, liquid) will be readily available. Vitamin A is traditionally formulated in oral formulations and, most commonly and cost-effectively, capsules. Questions loom—how do you give larger-than-usual vitamin A doses to infants or children who cannot swallow capsules? Insurance coverage for vitamin A may also be an issue because vitamin A is not a medication but a nutritional supplement.
Issue: Concerns About Vitamin A Toxicity
Summit participants emphasized the need to protect children with measles from further morbidity due to high vitamin A doses administered. “First, do no harm” was a commonly heard phrase during the Summit discussions.
Because vitamin A is fat soluble, the body stores excess amounts, and these levels can accumulate. If too much is stored, it can become toxic. The tolerable upper daily dose of 3000 μg of preformed vitamin A, more than 3 times the current recommended daily level, is thought to be safe. However, there is some evidence that this much preformed vitamin A might increase the risk of bone loss, hip fracture, or some birth defects.9 The potential for toxicity is real, although not commonly described in the literature. Part of the discussion at the Summit centered on the 1993 AAP Red Book Committee review of the vitamin A recommendations in measles management. The topic of vitamin A toxicity was explored because it was noted that potential toxicity occurred in cumulative doses of greater than 1,000,000 IU over 2 to 3 weeks. No reports of vitamin A toxicity in children with measles have been documented.19
Published reports on vitamin A acute toxicity between 1944 and 2000 show 55 cases (50 in ages 0–2 years). The lowest dose that caused toxicity in children aged 0 to 2 years was 11,500 IU/kg, and the median dose was 47,850 IU/kg.23 There seems to be no evidence of long-term consequences of the administration of high doses of vitamin A beyond nausea/diarrhea lasting 24 hours, which many children with measles have upon admission because of the virus, so the difference would be hard to detect. Symptoms of vitamin A toxicity are poor appetite, nausea, vomiting, diarrhea, sensitivity to light, and dry, rough skin,9 which are also common presenting symptoms of measles.
Issue: Parental Reliance on Potentially Inaccurate Word-of-Mouth Recommendations
Pockets of unvaccinated populations have been growing both in the United States and globally, because of lack of confidence in vaccines, allowing for outbreaks of vaccine-preventable diseases such as measles.
During the 2019 measles outbreak in New York, word-of-mouth recommendations advocating vitamin A prophylaxis propagated, regardless of measles exposure and as an alternative to MMR vaccination. Without properly combatting misinformation, this type of false information will continue to spread from outbreak to outbreak within vaccine-hesitant communities.20
OVERCOMING BARRIERS: RECOMMENDATIONS
Although the challenges are varied, 4 primary recommendations emerged that may help narrow the education and adherence gap.
Recommendation: Clarify AAP Red Book Recommendations on Vitamin A for Measles Management
Although there is notably more research to be done, current evidence suggests that the benefits of vitamin A for measles management outweigh the risks. The literature shows a significant benefit for reducing measles case fatality and severity by administering age-appropriate high-dose vitamin A supplements, without serious adverse effects.3,15,17 Thus, a healthcare professional making a clinical decision should consider prescribing high-dose vitamin A per WHO guidelines.
However, as currently written, the recommendations in the United States leave too much room for interpretation and should be clarified. Summit participants recommended that the AAP Red Book Committee consider clarifying the following:
- 1) Population: consider using either “all children” or “all hospitalized children”; consider removing terms such as “acute measles” and “severe measles,” which may not be helpful if the clinician has never seen measles.
- 2) Age range: do the recommendations apply to all children aged 0 to 18 years or only those younger than 5 years? Should adults with measles receive vitamin A?
- 3) Dosing: consider converting dosing to RAE and adding formulations.
- 4) Safety: consider providing clarity around safety of high doses of vitamin A.
Recommendation: Conduct Further Research on Vitamin A for Measles Management Within the United States
Measles is in a unique period in the United States, with an increased number of infections yet low outbreak case counts, making studies challenging. Nevertheless, a research agenda on the topic is imperative. The immunology behind vitamin A is complicated, and the lack of research on the impact of vitamin A on measles morbidity and mortality in the United States compared with the rest of the world is limited. Although the Summit participants acknowledge that healthcare professionals must make decisions based on the best available data, the group advocated for additional research moving forward.
The group recommended, as feasible, large-scale, randomized trials that evaluate the efficacy of a vitamin A protocol for use in hospitalized pediatric patients with measles in the United States. Assessing outpatients with mild to moderate measles and the impact that vitamin A might have on patient outcomes such as days of illness and immune impact would also be an important study.
Recommendation: Educate Healthcare Professionals About the Role of Vitamin A and MMR Vaccine in Measles Management
There are many ways we can educate healthcare professionals about guidelines for vitamin A for measles management and current low adherence rates including webinars, review articles, posters, and presentations at scientific conferences. The NFID is committed to educating healthcare professionals on measles prevention and management, including MMR vaccination as the best way to prevent measles and vitamin A as the best management approach to reduce complications from measles. The NFID encourages other organizations to join forces in these educational efforts.
Recommendation: Provide Clear, Direct Messaging to Parents About Measles Prevention and Management
The primary message to parents is clear: vitamin A does not prevent measles. The MMR vaccine is a safe and effective way to protect you and your family from measles. Parents should not forego MMR vaccine and instead use vitamin A as a preventive measure. Opportunities exist to
- ▪ educate parents about vaccines and, specifically, MMR vaccine;
- ▪ clearly state what is known to be effective in measles management (vitamin A) and what is not (vitamin C, vitamin D, selenium, etc);
- ▪ explain that vitamins are not all alike and should not be conflated for the treatment of measles and that parents should consult with healthcare professionals for measles management; and
- ▪ educate about good sources of vitamin A (eg, a healthy diet). Adequate dietary vitamin A intake is very important to support the immune system and should be used with vaccination, not as a substitute for vaccination.
After carefully considering the risks and benefits, Summit participants agreed that the US recommendations should include the following:
- ▪ Vitamin A should be prescribed for pediatric patients in the United States with a confirmed measles diagnosis. A thorough history of recent vitamin A supplementation should be taken before recommending vitamin A.
- ▪ At the time of diagnosis, vitamin A should be given by mouth once daily for 2 days at the following age-based doses:
- ▪ 200,000 IU for children 12 months or older (60,000 μg RAE)
- ▪ 100,000 IU for infants 6 through 11 months old (30,000 μg RAE)
- ▪ 50,000 IU for infants younger than 6 months (15,000 μg RAE)
- ▪ An additional dose should be given in 2 to 4 weeks for children known to be previously vitamin A deficient or those who have eye complications caused by measles.
- ▪ These recommendations are based on studies demonstrating improvements in mortality and morbidity from children with measles in resource-limited countries; there were limited adverse events in these trials.
- ▪ Measles infection is associated with inducing a decrease of vitamin A, which is necessary for immune function and epithelial cell integrity.
With the increased number of measles cases in the United States, guidelines in place, and the benefits of vitamin A documented, now is the time to urgently disseminate this information to healthcare professionals and the public.
The bottom line is that all children in the United States presenting with measles should receive an age-appropriate dose of vitamin A as part of a comprehensive measles management protocol. Multiple studies in populations in which vitamin A deficiency is prevalent have shown that this simple, quick means of improving vitamin A status can dramatically reduce the risk of serious complications and death from measles, with minimal detectable incidence of adverse effects.
In addition, the AAP and other professional organizations need to revisit their guidelines to provide the utmost clarity to healthcare professionals.
Finally, a research agenda for better understanding the mechanism of vitamin A in measles management within the United States, and other resource-rich countries, needs to be established.
Now is the time for action: professional associations and medical experts on the front lines of infection prevention and control are stewards of public health. Implementation of the recommendations outlined in this article must be considered. It is a shared responsibility to protect and educate our communities on how to best manage the impact of measles as a vaccine-preventable disease.
In addition to the authors, Patricia A. Stinchfield, MS, RN, CPNP, CIC, NFID Vice President, and Walter A. Orenstein, MD, NFID Past President, the following individuals participated in the November 2019 National Foundation for Infectious Diseases (NFID) Measles and Vitamin A Summit, which served as the basis for this article:
Henry H. Bernstein, DO: Professor of Pediatrics, Zucker School of Medicine at Hofstra/Northwell Cohen Children's Medical Center; Current Advisory Committee on Immunization Practices Voting Member
James D. Campbell, MD, MS: Professor, Division of Infectious Diseases and Tropical Pediatrics, Department of Pediatrics, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
Amanda C. Cohn, MD: Executive Secretary, Advisory Committee on Immunization Practices, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention
Kathleen Harriman, PhD, MPH, RN: Section Chief, Vaccine Preventable Disease Epidemiology, California Department of Public Health
Gabrielle Z. Hester, MD, MS: Medical Director of Clinical Outcomes and Pediatric Hospitalist, Children's Minnesota
Neal A. Halsey, MD: Professor Emeritus and Director Emeritus, Institute for Vaccine Safety, Johns Hopkins Bloomberg School of Public Health
Blima Marcus, DNP, RN, ANP-BC, OCN: Nurse Practitioner, Memorial Sloan Kettering Cancer Center; and Adjunct Professor, Hunter-Bellevue School of Nursing
Michael J. Mina, MD, PhD: Assistant Professor of Epidemiology and Assistant Professor in Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health; Associate Medical Director, Clinical Microbiology and Molecular Virology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School
Jill A. Morgan, PharmD, BCPS, BCPPS: Chair, Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy
Adam J. Ratner, MD, MPH: Associate Professor of Pediatrics and Microbiology and Chief, Division of Pediatric Infectious Diseases, New York University School of Medicine
Jennifer B. Rosen, MD: Director, Epidemiology & Surveillance, Bureau of Immunization, New York City Department of Health and Mental Hygiene
Alfred Sommer, MD, MHS: Dean Emeritus and Professor, Department of Epidemiology, International Health, Bloomberg School of Public Health; Ophthalmology, School of Medicine
Alicen B. Spaulding, PhD, MPH: Scientific Investigator, Children's Minnesota Research Institute
The NFID would also like to thank Julia L. Hurwitz, PhD, from St. Jude Children's Research Hospital for her contributions.
1. Centers for Disease Control and Prevention. Measles (Rubeola). For Healthcare Professionals. 2019. Available at: https://www.cdc.gov/measles/index.html
. Accessed February 28, 2020.
2. Centers for Disease Control and Prevention. Measles cases and outbreaks. 2019. Available at: https://www.cdc.gov/measles/cases-outbreaks.html
. Assessed February 28, 2020.
3. Hussey GD, Klein M. A randomized, controlled trial of vitamin A in children with severe measles. N Engl J Med
4. Measles vaccines: WHO position paper. Wkly Epidemiol Rec
5. Perry RT, Halsey NA. The clinical significance of measles: a review. J Infect Dis
. 2004;189(suppl 1):S4–S16.
6. Joint WHO/UNICEF statement on vitamin A for measles. Wkly Epidemiol Rec
7. Kimberlin DW, Brady MT, Jackson MA, Long SS eds. Red Book: 2018 report of the committee on infectious diseases
. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018:537–550.
8. Hester GZ, Nickel AJ, Stinchfield PA, et al. Demographics, complications and resource utilization for patients hospitalized for measles across US children's hospitals. Pediatr Infect Dis J
9. National Institutes of Health: Office of Dietary Supplements. Vitamin A: fact sheet for healthcare professionals. Available at: http://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/
Accessed February 28, 2020.
10. Centers for Disease Control and Prevention. Second nutrition report. 2012. Available at: https://www.cdc.gov/nutritionreport/report_2012.htm
. Accessed February 28, 2020.
11. Diab L, Krebs N. Vitamin excess and deficiency. Pediatr Rev
12. Butler JC, Havens PL, Sowell AL, et al. Measles severity and serum retinol (vitamin A) concentration among children in the United States. Pediatrics
13. Arrieta AC, Zaleska M, Stutman HR, et al. Vitamin A levels in children with measles in Long Beach, California. J Pediatr
14. Frieden TR, Sowell AL, Henning KJ, et al. Vitamin A levels and severity of measles. New York City. Am J Dis Child
15. Ellison JB. Intensive vitamin therapy in measles. Br Med J
16. Sommer A, Tarwotjo I, Djunaedi E, et al. Impact of vitamin A supplementation on childhood mortality. A randomised controlled community trial. Lancet
17. Barclay AJ, Foster A, Sommer A. Vitamin A supplements and mortality related to measles: a randomized clinical trial. Br Med J
18. Sommer A, Hussaini G, Tarwotjo I, et al. Increased mortality in children with mild vitamin A deficiency. Lancet
19. Committee on Infectious Diseases. American Academy of Pediatrics Committee on Infectious Diseases: vitamin A treatment of measles. Pediatrics
20. Marcus B. Presentation: measles outbreak NYC: 2018–2019 Lessons Learned. NFID Measles in Vitamin A Summit
. November 18, 2019.
21. Government of Samoa. Measles outbreak 2019. Available at: http://www.samoagovt.ws/
. Accessed February 28, 2020.
22. Yang HM, Mao M, Wan C. Vitamin A for treating measles in children. Cochrane Database Syst Rev
23. Myhre A, Carlsen M, Bøhn S, et al. Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations. Am J Clin Nutr