Measles Pneumonitis Following Measles-Mumps-Rubella Vaccination of a Patient with HIV Infection, 1993

The Advisory Committee on Immunization Practices (ACIP) recommends measles-mumps-rubella vaccine (MMR) for all persons asymptomatically infected with human immunodeficiency virus (HIV) and recommends that MMR be considered for all symptomatic HIV-infected persons who would otherwise be eligible for measles vaccine, because measles virus infection can cause severe illness and death in such persons (1,2). Serious or unusual adverse events in HIV-infected persons after receiving MMR have not been reported previously (1,2). This report summarizes the investigation of a case of progressive vaccine-associated measles pneumonitis in a person with acquired immunodeficiency syndrome and provides interim recommendations for the use of measles-containing vaccine among HIV-infected persons.

On September 3, 1992, a 20-year-old man with hemophilia A and HIV infection received MMR to fulfill a college prematriculation vaccination requirement for a second dose of measles-containing vaccine. He had received a previous dose of measles vaccine in 1973. His CD4+ T-lymphocyte count was reported as "too few to enumerate" in January, March, and August 1992. At the time of vaccination, he did not have HIV-related symptoms and was not taking antiretroviral therapy or prophylactic treatment for Pneumocystis carinii pneumonia (PCP).

On October 2, the patient was hospitalized because of increasing shortness of breath and dyspnea on exertion, and on October 5, PCP was diagnosed by methenamine silver stain following bronchoscopy with bronchoalveolar lavage. Therapy with intravenous pentamidine was initiated, and on October 8 the patient was discharged to complete treatment as an outpatient. His pulmonary symptoms resolved, and he was followed as an outpatient through November 1992, when he was lost to follow-up.

On July 30, 1993, he visited his physician and reported onset of night sweats, chills, and a nonproductive cough. Chest radiograph demonstrated lingular and left lower lobe infiltrates. Outpatient treatment with atovaquone for presumptive PCP was initiated and continued until August 20 without improvement. On August 31, he was hospitalized because of worsening dyspnea, fever, nonproductive cough, and weight loss. Chest radiography revealed patchy infiltrates in the left lung and pleural effusion. Despite empiric treatment for PCP, fungal infection, Mycobacterium avium complex (MAC) disease, and other bacterial infections, he remained febrile without clinical improvement. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy on September 2 and September 23 did not provide a specific diagnosis, and cultures of pleural fluid were negative for bacterial, fungal, mycobacterial, and viral pathogens.

On October 6, an open-lung biopsy was performed. Biopsy specimens revealed numerous multinucleate giant cells, some of which contained both intranuclear and cytoplasmic eosinophilic inclusions suggestive of viral infection. A presumptive diagnosis of measles pneumonia was made, and therapy with intravenous gamma globulin was started. On October 22, measles virus was identified from tissue-culture cells inoculated with the lung biopsy tissue, and ribavirin therapy was initiated on October 23. The patient's condition stabilized, and he was discharged on October 29.

On November 12, he was hospitalized because of nausea and vomiting, increasing shortness of breath, and left upper quadrant abdominal pain. Chest radiograph demonstrated a right-sided nodular infiltrate and a left pneumothorax with effusion. The patient received treatment for presumptive MAC disease and esophageal candidiasis, and prophylaxis for PCP. A chest drainage catheter was placed and then removed before the patient was discharged on November 23.

On November 27, when he was hospitalized because of nausea, vomiting, and dehydration, chest radiograph demonstrated residual pneumothorax. Parenteral nutrition was initiated, and he was treated for presumptive MAC infection. Subsequent chest radiography demonstrated increased bilateral pulmonary infiltrates. Following the onset of encephalopathic changes on December 13, he died on December 17. No autopsy was performed.

The reported immediate cause of death was cytomegalovirus (CMV) encephalitis; pulmonary measles and MAC infection were listed as contributing causes. The diagnoses of CMV and MAC infection were based on clinical findings without laboratory confirmation.

The measles virus isolate recovered on October 22 from the patient's lung biopsy tissue was propagated in tissue-culture cells. Selected regions of the viral genome RNA were reverse transcribed, amplified by polymerase chain reaction, and subjected to sequence analysis, revealing a high degree of similarity to the Moraten measles vaccine virus strain. In 1995, the genomes of both the patient's virus isolate and the Moraten vaccine virus strain were completely sequenced and differed by only two nucleotides, each encoding an amino acid change. The essential identity of these two measles virus strains confirmed Moraten vaccine strain as the source of the virus isolated from the lung biopsy specimen. CDC was notified of these findings in March 1996, and supplemental sequence studies performed at CDC support the conclusion that Moraten vaccine was the source for the measles virus isolate.

Reported by: JB Angel, MD, SA Udem, MD, DR Snydman, MD, ME Keenan, MD, JT Noble, MD, RA DeLellis, MD, VA Sacco, MS, JL Hadler, MD, State Epidemiologist, Connecticut State Dept of Health. SM Lett, MD, A DeMaria, Jr, MD, State Epidemiologist, Massachusetts Dept of Public Health. Div of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention; Respiratory and Enteroviruses Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases; Child Vaccine Preventable Diseases Br, Epidemiology and Surveillance Div, National Immunization Program, CDC.

Editorial Note

Editorial Note: This report is the first known case of a serious adverse event following the documented administration of a measles-containing vaccine to a severely immunocompromised person with HIV infection. Serious adverse events after receipt of measles vaccine by persons with severe immunosuppression attributable to causes other than HIV infection have been reported previously (3), and measles vaccination is contraindicated in such persons. The case described in this report also is unusual because the patient did not have clinical onset of measles pneumonitis until almost 1 year after vaccination -- a finding also not previously reported.

ACIP recommends the routine administration of MMR at age 12-15 months and a second dose at ages 4-6 years or 11-12 years (4). Adults without evidence of measles immunity should receive at least one dose of measles-containing vaccine (preferably MMR) unless otherwise contraindicated (5). Persons can be considered immune to measles if they 1) were born before 1957; 2) have documentation of physician-diagnosed measles; 3) have laboratory evidence of immunity to measles; or 4) have documentation of adequate vaccination (5).

Because of the increased risk for severe complications associated with measles infection and the absence of serious adverse events after measles vaccination among HIV-infected persons (1,2), ACIP has recommended that MMR be administered to all asymptomatic HIV-infected persons and that MMR be considered for administration to all symptomatic HIV-infected persons who would otherwise be eligible for measles vaccine -- even though the immune response may be attenuated in such persons (1,2,5). There is a theoretical risk for an increase (probably transient) in HIV viral load following MMR vaccination because such effects have been observed with other vaccines (6). Specific studies of the effect, if any, of MMR vaccination on viral load are needed. Because of the case described in this report and other evidence indicating a diminished antibody response to measles vaccination among severely immunocompromised persons (7), ACIP is reevaluating the recommendations for vaccination of severely immunocompromised persons with HIV infection. In the interim, it may be prudent to withhold MMR or other measles containing vaccines from HIV-infected persons with evidence of severe immunosuppression, defined as 1) CD4+ T-lymphocyte counts less than 750 for children aged less than 12 months, less than 500 for children aged 1-5 years, or less than 200 for persons aged greater than or equal to 6 years; or 2) CD4+ T-lymphocytes constituting less than 15% of total lymphocytes for children aged less than 13 years (8,9).

ACIP continues to recommend MMR for HIV-infected persons without evidence of measles immunity (5) who are not severely immunocompromised (8,9). Severely immunocompromised HIV-infected patients who are exposed to measles should receive immune globulin (IG), regardless of prior vaccination status (1). In addition, health-care providers should weigh the risks and benefits of measles vaccination or IG prophylaxis for severely immunocompromised HIV-infected patients who are at risk for measles exposure because of outbreaks or international travel.

Because the immunologic response to both live and killed antigen vaccines may decrease as HIV disease progresses (1,10), vaccination early in the course of HIV infection may be more likely to induce an immune response. Therefore, HIV-infected infants without severe immunosuppression should routinely receive MMR as soon as possible after their first birthday. Evaluation and testing of asymptomatic persons to identify HIV infection are not necessary before deciding to administer MMR or other measles-containing vaccine (1).

References

1. CDC. Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence. MMWR 1993;42(no. RR-4):1-12.

2. CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1994;43(no. RR-1).

3. Mitus A, Holloway A, Evans AE, Enders JF. Attenuated measles vaccine in children with acute leukemia. Am J Dis Child 1962;103:243-8.

4. CDC. Recommended childhood immunization schedule -- United States, January-June 1996. MMWR 1996;44:940-3.

5. CDC. Measles prevention: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1989;38(no. S-9).

6. Stanley SK, Ostrowski MA, Justement JS, et al. Effect of immunization with a common recall antigen on viral expression in patients infected with human immunodeficiency virus type 1. N Engl J Med 1996;334:1222-30.

7. Palumbo P, Hoyt L, DeMasio K, Oleske J, Connor E. Population-based study of measles and measles immunization in human immunodeficiency virus-infected children. Pediatr Infect Dis J 1992;11:1008-14.

8. CDC. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 1992;41(no. RR-17).

9. CDC. 1994 Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR 1994;43(no. RR-12):1-10.

10. Arpadi SM, Markowitz LE, Baughman AL, et al. Measles antibody in vaccinated human immunodeficiency virus type 1-infected children. Pediatrics 1996;97:653-7.

    
    

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