Measles vaccination of special risk groups

ABSTRACT

Measles is a highly transmissible viral vaccine preventable infection that causes significant morbidity and mortality to both children and adults. Before the implementation of universal vaccination, measles was affecting entire birth cohorts during childhood. Large outbreaks would occur every 2–3 years during late winter or early spring, as the number of susceptible individuals in the community increased. Measles vaccine has been available for more than 50 years and universal use of the vaccine has significantly decreased the incidence of this VPD worldwide.¹ High vaccine coverage (>95%) with two doses of measles-containing vaccine is necessary to ensure adequate level of population immunity to interrupt disease circulation and achieve elimination.² Measles eradication has not been achieved since universal high vaccination coverage has not been reached. Moreover, outbreaks continue to occur worldwide, even in areas with high vaccination coverage, mainly affecting infants too young to be vaccinated and unvaccinated older subjects.

One of the most important issues that needs attention is the growing body of parental vaccine hesitancy. Lack of knowledge, religious objections, and most of all concerns of vaccine safety including fear that vaccines may weaken the immune system or induce chronic diseases, are the leading causes of parental vaccine hesitancy.³ Additionally, while measles cases have significantly decreased over the past 18 months in most areas of the world, possibly due to mitigation measures aiming to decrease SARS-CoV-2 transmission, vaccination programs have been variably disrupted at the same time. However, decrease in vaccination coverage can lead to an increase of vulnerable children and potentially lead to large outbreaks in the future.⁴

Recent outbreaks in Europe and the United States have clearly shown that subjects at increased risk for adverse events post measles vaccination often remain unvaccinated and thus are at great risk once measles outbreaks ensue. Limited clinical data on adverse events among special groups of subjects at increased risk following immunization, such as children with underlying diseases, increases vaccine hesitancy among these groups.³

The aim of this article is to review available data on vaccine safety in groups of subjects at increased risk for adverse events following measles immunization (AEFI).

Children with known neurologic disorders

The occurrence of febrile seizures (FS) postmeasles vaccination has been well recognized and is most likely associated with the vaccine-induced fever. FS mainly occur during the second week following the administration of the first vaccine dose in young children during their second year of life with an estimated incidence of one case for every 3000–4000 doses of MMR vaccine administered.^4,5 Measles-containing vaccine has been found to increase the incidence of FS during the second year of life by 25–34.2 per 100,000 children.⁶ Importantly, children experiencing their first FS after MMR vaccination are not at increased risk of recurrent seizures. As expected, a population-based study showed that children with a personal history of febrile seizures have an increased risk of developing febrile seizures post measles vaccination.⁷ Moreover, siblings of children with known epilepsy had a marginally increased risk of febrile seizures post measles-containing vaccination.⁷ Of note, the receipt of measles-containing vaccine is not associated with any long-term adverse outcome or increased incidence of epilepsy even in those children presenting with febrile seizures post vaccination.⁷ Importantly, in a review of children with seizures post vaccination and subsequent diagnosis of epilepsy, genetic, or structural defects were often identified as underlying cause of epilepsy indicating that measles vaccine only brought earlier to medical attention an existing health issue.⁸ Recently, due to an ongoing outbreak in Greece in 2017–2018, we offered measles vaccination to a cohort of unvaccinated children with severe underlying neurologic diseases, including pharmacoresistant epilepsy, severe pervasive developmental disorder and severe neurogenetic diseases. Among 27 vaccinated children, almost half presented with febrile or afebrile seizures, indicating that measles vaccination resulted in seizure aggravation in children with known epileptic disease. Importantly, however, no child needed adjustment of their antiepileptic treatment or exhibited developmental regression. We concluded that benefits of administering measles-containing vaccine in children with severe neurologic disease outweighs the risks and parents should be supported and advised to immunize their children.⁹ However, when addressing parents of children with known epilepsy or with a personal or family history of febrile seizures, it is advisable to inform them of the known increased risk of febrile seizures post administration of the combined MMR and varicella (MMRV) vaccine, especially for the first dose administered during the second year of life.¹⁰

Children with thrombocytopenia or immune thrombocytopenic purpura

The administration of measles-containing vaccines has been associated with the development of immune thrombocytopenic purpura (ITP), during the 6 weeks postimmunization. Possible mechanism involves the development of antimeasles antibodies cross reacting with platelets’ antigens.⁵ The likelihood of developing ITP post measles-containing vaccine has been estimated 2.6/100,000 vaccine doses (range, 0.087–4) and is lower than that post viral disease.^5,11 Although, the clinical outcome of ITP after vaccination is less severe than ITP observed after natural measles disease, there have been isolated reports of cases requiring hospitalization. It is important to note however, that MMR vaccination of unimmunized patients with previous history of ITP as well as revaccination of patients with prior vaccine-induced ITP did not lead to recurrence of thrombocytopenia.¹¹ However, in children with chronic ITP the risk-benefit ratio of MMR vaccination should be weighted based on local measles epidemiology.¹⁰

Children with known allergies

Although anaphylaxis following immunization is a rare phenomenon, estimated to occur in about 1.3/10⁶ doses, several vaccines have been found to be associated with severe allergic reactions.¹² A causal association between measles vaccine and anaphylaxis in children with egg allergy was firmly believed for years.¹² However, nowadays it has been clearly shown that it is safe to administer measles-containing vaccines to children with known egg allergy since the amount of residual ovalbumin from hen’s egg is minimal.^13,14 In the contrary, measles-containing vaccines contain traces of gelatin and neomycin and thus children with a history of anaphylaxis due to allergy to these components should be vaccinated in health centers able to manage severe allergic reactions.^5,10 However, neomycin allergy most often manifests as a delayed type or cell-mediated immune response (i.e. a contact dermatitis) rather than as anaphylaxis.⁵ Clearly, a second dose of measles-containing vaccine cannot be administered to children with a previous history of anaphylaxis post MMR.

Children with chronic diseases

Children with chronic diseases such as children with chronic liver, kidney, pulmonary, or heart diseases may often remain underimmunized due to complicated clinical care and treatment regimens, frequent hospitalizations and parental anxiety.¹⁵ Moreover, responses to immunization in such patients might be reduced.

In a small study, only 70% of children with chronic renal failure on dialysis developed protective titers against measles post MMR administration. Moreover, only 30% of children responded to all three components indicating that in such children monitoring of immune response should follow immunization.¹⁶

On the other hand, a recent study in asthmatic children indicated that measles antibody titers waned more rapidly when compared to healthy children, resulting in lower antibody concentration and lower seropositivity rate in asthmatics than non-asthmatics starting around 9.3 years after the initial measles vaccination.¹⁷ However, potential mechanism and clinical significance of this observation remain unknown.

Children with immunosuppression

Measles vaccines contain live attenuated virus and therefore administration to children or adults with severe immunosuppression is contraindicated due to the fear of vaccine-virus induced severe infection. Additionally, measles-containing vaccines may be less effective when administered to a subject with impaired immune system. On the other hand, immunocompromised patients are the ones mostly at need to be protected since they are especially vulnerable from infections. These would include children with primary or acquired immunodeficiency, persons with blood dyscrasias, leukemia or other malignant neoplasms affecting bone marrow or lymphatic system, and persons receiving systemic immunosuppressive therapy.⁵ Although in the late 1990s, there were three case reports on immunocompromised children developing inclusion body encephalitis post MMR vaccine, there have not been further reports.^5,9

Additionally, nowadays an increased number of young children receive immunomodulating treatment for a variety of autoimmune, rheumatologic, and inflammatory bowel diseases or undergo bone marrow (BMT) or solid organ transplantation (SOT). Therefore, clinicians often face the challenge of vaccinating these children with live attenuated vaccines. Guidelines on when to vaccinate different group of pediatric patients have been issued by different societies but significantly vary since data on safety and immunogenicity post MMR immunization is scarce.^18–22 A recent systematic review of the literature examined available data on the safety and immunogenicity and effectiveness of live vaccination in such patients.²³ Although proliferation of the attenuated vaccine strain has been rarely reported post MMR vaccination in subjects with immune mediated inflammatory diseases (0.2%) and post SOT (1.2%), no serious adverse events have been reported. However, while no aggravation of disease has been reported in a small study of patients with juvenile idiopathic arthritis (JIA), there have been case reports of children with SOT presenting with acute rejection as well as malignancy relapse post MMR vaccination.^24,25 Results from immunogenicity studies among children with inflammatory diseases, mainly JIA, are controversial since in some but not all a decreased humoral and cellular immune response has been found when compared to healthy children.²³ Children previously immunized with MMR who undergo BMT are more likely to lose their immunity post BMT when compared to adults.²⁵ Moreover, immune response to measles appears lower when compared to rubella among children vaccinated post SOT and BMT²⁶. This is especially true for children vaccinated within 15 months post BMT.²³ Importantly, few small studies have examined clinical efficacy post MMR vaccination of immunosuppressed subjects with a follow-up of up to 12.5 years. No breakthrough infections have been reported, indicating good protection from vaccination.

Finally, when HIV-infected children are considered, although before the availability of effective antiretroviral treatment (ART), responses to MMR vaccine were suboptimal, recent studies have indicated that when ART is initiated before MMR vaccination, both humoral and cellular immune responses are comparable to those of healthy children. Therefore, all HIV-infected children should receive two doses of MMR (MMRV has not been studied in children with HIV infection) unless they have evidence of severe immunosuppression.⁵ In children vaccinated with MMR before the administration of ART, revaccination should be considered if no serologic evidence of immunity is available. Importantly, long-term immunogenicity is associated with keeping children on ART at the time of booster vaccination.²⁷

Children living with adults at high risk or pregnant women

When vaccinating children residing with immunocompromised subjects or pregnant women the issue of potential transmission of the vaccine virus from the vaccinee to their susceptible household may arise. However, it should be stressed that such a transmission has never been reported post measles vaccination.⁵ Therefore, it needs to be stressed that measles vaccine should be administered according to the Immunization Program to all children living with immunocompromised subjects to protect their relatives using the cocooning care model. Additionally, measles-containing vaccination should not be postponed in children of nonimmune pregnant women.

Conclusions

Universal measles vaccination has significantly decreased the incidence of this important vaccine preventable disease worldwide. Although it is a safe and effective vaccine, less than 95% of children timely receive their two doses as recommended by WHO. There are well defined patient groups in which the administration of measles-containing vaccine is contraindicated including children with prior anaphylaxis to gelatin, neomycin, or MMR vaccination or children with severe immunosuppression. Still many misconceptions drive underimmunization or vaccination delay in children at need of the vaccine. The role of primary-care providers is essential in addressing common misconceptions.

Funding Statement

The author(s) reported there is no funding associated with the work featured in this article.

References