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The Immunization Practices Advisory Committee (ACIP) recently reviewed data both on the risks and benefits of immunizing children infected with human immunodeficiency virus (HIV) (1) and on severe and fatal measles in HIV-infected children in the United States (2). Since this review, the committee has revised its previous recommendations for measles vaccination and for mumps and rubella vaccination.

Previously published ACIP statements on immunizing HIV-infected children have recommended vaccinating children with asymptomatic HIV infection, but not those with symptomatic HIV infection (3). After considering reports of severe measles in symptomatic HIV-infected children, and in the absence of reports of serious or unusual adverse effects of measles, mumps, and rubella (MMR) vaccination in limited studies of symptomatic patients (4,5), the committee feels that administration of MMR vaccine should be considered for all HIV-infected children, regardless of symptoms. This approach is consistent with the World Health Organization's recommendation for measles vaccination (6).

If the decision to vaccinate is made, symptomatic HIV-infected children should receive MMR vaccine at 15 months, the age currently recommended for vaccination of children without HIV infection and for those with asymptomatic HIV infection. When there is an increased risk of exposure to measles, such as during an outbreak, these children should receive vaccine at younger ages. At such times, infants 6 to 11 months of age should receive monovalent measles vaccine and should be revaccinated with MMR at 12 months of age or older. Children 12-14 months of age should receive MMR and do not need revaccination (7).

The use of high-dose intravenous immune globulin (IGIV) (approximately 5 gm% protein) administered at regular intervals is being studied to determine whether it will prevent a variety of infections in HIV-infected children. It should be recognized that

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES/PUBLIC HEALTH SERVICE

U.S. DEPOSITORY MAY 6 19

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MMR vaccine may be ineffective if administered to a child who has received IGIV during the preceding 3 months.

Immune globulin (IG) (16.5 gm% protein) can be used to prevent or modify measles infection in HIV-infected children if administered within 6 days of exposure. IG is indicated for measles-susceptible* household contacts of children with asymptomatic HIV infection, particularly for those under 1 year of age and for measlessusceptible pregnant women. The recommended dose is 0.25 mL/kg intramuscularly (maximum dose, 15 mL) (7).

In contrast, exposed symptomatic HIV-infected patients should receive IG prophylaxis regardless of vaccination status. The standard postexposure measles prophylaxis regimen for such patients is 0.5 mL/kg of IG intramuscularly (maximum dose, 15 mL) (7). This regimen corresponds to a dose of protein of approximately 82.5 mg/kg (maximum dose, 2,475 mg). Intramuscular IG may not be necessary if a patient with HIV infection is receiving 100-400 mg/kg IGIV at regular intervals and received the last dose within 3 weeks of exposure to measles. Based on the amount of protein that can be administered, high-dose IGIV may be as effective as IG given intramuscularly. However, no data exist on the efficacy of IGIV administered postexposure in preventing measles.

Although postexposure administration of globulins to symptomatic HIV-infected patients is recommended regardless of measles vaccine status, vaccination prior to exposure is desirable. Measles exposures are often unrecognized, and postexposure prophylaxis is not always possible.

While recommendations for MMR vaccine have changed, those for other vaccines have not (3). A summary of the current ACIP recommendations for HIV-infected persons follows (Table 1). These recommendations apply to adolescents and adults with HIV infection as well as to HIV-infected children.

*Persons who are unvaccinated or do not have laboratory evidence or physician documentation of previous measles disease (7).

TABLE 1. Recommendations for routine immunization of HIV-infected children United States, 1988*

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*DTP

=

*See accompanying text and previous ACIP statement (3) for details.
Diphtheria and tetanus toxoids and pertussis vaccine.
$OPV = Oral, attenuated poliovirus vaccine; contains poliovirus types 1, 2, and 3.
IPV Inactivated poliovirus vaccine; contains poliovirus types 1, 2, and 3.
**MMR = Live measles, mumps, and rubella viruses in a combined vaccine.
**Should be considered.

=

$$HbCV Haemophilus influenzae type b conjugate vaccine.

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1. von Reyn CF, Clements CJ, Mann JM. Human immunodeficiency virus infection and routine childhood immunisation. Lancet 1987;2:669-72.

2. Centers for Disease Control. Measles in HIV-infected children - United States. MMWR 1988;37:183-186.

3. Immunization Practices Advisory Committee. Immunization of children infected with human T-lymphotropic virus type III/lymphadenopathy-associated virus. MMWR 1986:35:

595-8,603-6.

4. McLaughlin P, Thomas PA, Onorato I, et al. Use of live virus vaccines in HIV-infected children: a retrospective survey. Pediatrics (in press).

5. Krasinski K, Borkowsky W, Krugman S. Antibody following measles immunization in children infected with human T-cell lymphotropic virus-type III/lymphadenopathy associated virus (HTLV-III/LAV) [Abstract]. In: Program and abstracts of the International Conference on Acquired Immunodeficiency Syndrome, Paris, France, June 23-25, 1986.

6. Global Advisory Group, World Health Organization. Expanded programme on immunization. Wkly Epidem Rec 1987;62:5-9.

7. Immunization Practices Advisory Committee. Measles prevention. MMWR 1987;36: 409-18,423-5.

Epidemiologic Notes and Reports

Measles in HIV-Infected Children, United States

The Centers for Disease Control has received reports of six cases of measles that occurred among children infected with human immunodeficiency virus (HIV) in the United States during the period 1986-1987 (Table 1). Two of these children died from measles. Like many other infections, measles appears to be more severe in persons with HIV infection.

Patients 1-3 became ill during a nosocomial outbreak in a New York City hospital (1). These patients had acquired HIV infections perinatally. None had received measles vaccine nor were they receiving intravenous immune globulin

TABLE 1. Cases of measles in children infected with HIV

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*For classification criteria, see MMWR 1987;36:225-35(2).

*Postexposure prophylaxis with immune globulin more than 6 days after exposure.

"Evanescent rash with Koplik spots.

"Postexposure prophylaxis with varicella-zoster immune globulin more than 6 days after

exposure.

**For classification criteria, see MMWR 1986;35:334-9 (3).

**Probable exposure in an emergency room.

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(IGIV). All were assumed to have had a common source of exposure to measles in the hospital, but the source was never identified. A medical student, who probably acquired disease from the same source, developed a rash several days before the children did. The medical student, whose rash illness was initially thought to be varicella because she recently had been exposed to a patient with varicella, had contact with the HIV-infected patients. Consequently, Patient 2 received varicellazoster immune globulin (VZIG), and Patient 1 received intramuscular immune globulin (IG). Both patients developed measles within several days of globulin administration and thus may have received globulins more than 6 days after exposure. Patient 1, a 7-month-old with HIV class P-0 infection (indeterminant), and Patient 3, a 4-year-old with HIV class P-2, subclass D-1 infection (cryptosporidiosis) (2), had typical measles illnesses with cough, coryza, conjunctivitis, Koplik spots, and rash. Patient 1 had a measles hemagglutination-inhibition (HI) antibody titer of 10 on the first day of rash (due either to residual, passively transferred maternal antibody or to passive immunization). Patient 2, a 2-year-old with HIV class P-2, subclass D-2 infection (recurrent bacterial infections), had only a transient rash and Koplik spots. Both Patients 2 and 3 developed severe pneumonia and were treated with aerosolized ribavirin (4). Patient 3 died, and autopsy showed diffuse giant-cell pneumonia typical of measles infection consisting of multinucleate giant cells with nuclear and cytoplasmic inclusions (5).

Patient 4, a 2-year-old with perinatally acquired HIV infection, had HIV class P2, subclass A infection (hepatosplenomegaly, generalized lymphadenopathy, and herpes stomatitis) at the time of onset of measles. She acquired measles during hospitalization at a different hospital in New York City. The source of her infection was not determined. This patient had never been vaccinated against measles and was not receiving IGIV. She developed generalized rash, fever, coryza, conjunctivitis, Koplik spots, and otitis media but no other complications.

Patient 5, a 4-year-old child with perinatally acquired HIV class P-2, subclass C infection (lymphoid interstitial pneumonitis), was admitted with fever and pneumonia to a hospital in Miami, Florida. The patient had never been vaccinated against measles but was receiving IGIV (200 mg/kg) prophylactically every month. The last dose had been received 3 weeks before onset of illness. Her measles antibody titer at the time of onset of illness is not known. The patient developed respiratory failure and died 8 days after admission. There was no history of rash. The diagnosis of measles pneumonia was made on postmortem examination of lung tissue that showed multinucleate giant cells with nuclear and cytoplasmic inclusions. This patient was not isolated during her hospitalization, and nosocomial transmission of measles resulted: a pediatric nurse and a patient, neither of whom had been vaccinated, acquired measles from the child. One additional patient acquired infection from the

nurse.

Patient 6, a 14-year-old with HIV Group IV infection (thrombocytopenia) (3), had acquired HIV as a result of a blood transfusion. He had been immunized with live, attenuated measles vaccine at 15 months and again at 9 years of age. The patient was admitted to a hospital with fever and later developed rash and pneumonia. Measles was serologically confirmed. The patient was treated with aerosolized ribavirin and recovered without sequelae.

Reported by: K Krasinski, MD, W Borkowsky, MD, S Chandwani, MD, R Lawrence, MD, New York Univ Medical Center-Bellevue Hospital Center; S Friedman, MD, MPH, New York City Dept of

Measles - Continued

Health; DL Morse, MD, MS, State Epidemiologist, New York State Dept of Health. C Mitchell, MD, G Scott, MD, K Roach, E Roldan, MD, M Saldana, MD, Jackson Memorial Hospital, Miami; MH Wilder, MD, State Epidemiologist, Florida Dept of Health and Rehabilitative Svcs. AIDS Program, Center for Infectious Diseases; Div of Immunization, Center for Prevention Svcs, CDC. Editorial Note: In addition to these six measles cases in children with HIV infection, CDC has received reports of two measles cases in HIV-infected adults. Both survived the acute measles infection, although one was hospitalized. The two measles deaths involving HIV-infected children in 1987 were the first deaths due to measles in the United States to be reported to CDC since 1985. While there may be underreporting of nonhospitalized or nonfatal measles cases in persons with HIV infection, the case-fatality rate for measles in HIV-infected children is clearly higher than the case-fatality rate for measles in recent years in the United States, 0.1% (6).

Severe measles infections have been reported in other immunocompromised patients. Measles infection without rash has also been described (7). Physicians caring for patients with HIV infection should be aware that measles can be severe and may occur without the typical rash. This may preclude diagnosis and, thus, delay or prevent initiation of treatment, outbreak control measures, or appropriate hospital isolation. The fact that an unimmunized medical worker acquired measles from one of these cases and was involved in transmission to a hospitalized patient is noteworthy. In addition, five of the six measles cases in HIV-infected children were acquired in medical settings. Since hospital workers may acquire and/or transmit measles, hospitals should ensure that employees who may have occupational exposure to measles have proof of measles immunity (8).

During 1986 and 1987, large measles outbreaks occurred in urban areas of the United States among preschool-age children with low immunization levels (9). These areas (New York City, Jersey City, and Miami) also have high incidence rates of pediatric acquired immunodeficiency syndrome. Since HIV-infected children may live in areas where measles virus circulates because of low preschool measles immunization levels, they may be at higher risk of exposure to measles than other children in the United States.

As a result of these recent reports of measles in HIV-infected children, the Immunization Practices Advisory Committee (ACIP) now recommends that measles vaccine be considered for symptomatic as well as asymptomatic children with HIV infection (10). This approach to protect the HIV-infected child is consistent with the World Health Organization's recommendation to provide measles vaccination for all children in developing countries regardless of HIV and symptom status because of the high risk of measles and the severity of measles infection in general (11). References

1. Krasinski K, Holzman RS, Lacouture R, et al. Nosocomial measles: are current vaccination guidelines for staff adequate? [Abstract]. In: Program and abstracts of the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4-7, 1987. 2. Centers for Disease Control. Classification system for human immunodeficiency virus (HIV) infection in children under 13 years of age. MMWR 1987:36:225-30,235-6.

3. Centers for Disease Control. Classification system for human T-lymphotropic virus type Ill/lymphadenopathy-associated virus infections. MMWR 1986;35:334-9.

4. Banks G, Fernandez H. Clinical use of ribavirin in measles: a summarized review. In: Smith RA, Knight V, Smith JAD, eds. Clinical applications of ribavirin. New York: Academic Press, 1980:203-9.

5. Chandra RS. Giant cell pneumonia. Pediatr Pathol 1984;2:226-9.

6. Centers for Disease Control. Measles surveillance report no. 11, 1977-1981. Atlanta: US Department of Health and Human Services, Public Health Service, 1982.

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