Age: 1.08
Sex: M
Vaccine: HIBV, MMR
Symptoms: Lymphadenopathy, Nasal congestion, Oral intake reduced, Pyrexia, Rash morbilliform
Clinical narrative: Information has been received from three physicians, authors of a literature article concerning a 13 month old male patient who on an unspecified date was vaccinated with a dose of MMR (lot # unknown). Subsequently, the patient developed vaccine associated wild type measles and was hospitalized. Measles is an ubiquitous, highly contagious, seasonal disease affecting nearly every person in a given population by adolescence in the absence of an immunization program. Although remarkable control of measles has been achieved in some areas of the world since vaccine licensure in the 1960s and the enactment of school immunization laws in the 1990s, measles is still the leading cause of vaccine preventable deaths in children. The side effects after receipt of the live measles vaccine (alone or in combination with the mumps and rubella vaccine) are generally mild. There have been very few reported cases of the vaccine strain causing a typical measles-like illness. We report a child with fever and rash after MMR vaccination in whom diagnostic testing revealed the illness to be caused by the vaccine strain of measles. A 13 month old boy presented to the emergency department with a 2-day history of nasal congestion, fever as high as 40.2 C, and a rash. The rash began early in the morning as spots in on his forehead and spread caudad to included his entire body by 6 PM that same day. His mother reported that he had a cough, conjunctivitis, and decreased oral intake for 2 days prior to hospital admission. There had been no signs of pruritus or pain. His vital signs in the emergency department were a temperature of 40.1 C rectally, a pulse of 183, and a respiratory rate of 36. On physical examination, the child had bilaterally injected conjunctivae with mild discharge. A generalized erythematous papular eruption was seen over the entire body but was most dense on the face and trunk. Anterior cervical lymph nodes were enlarged bilaterally. Koplik spots were also noted. All routine laboratory values were normal except for his white blood count, which was elevated to 26.2 th/ul. Upon further questioning, the patient was found to have had a check up at his primary physician's office 10 days previously at which time he received his HIB vaccine and MMR. The child was admitted to the hospital for further evaluation of his rash and other constitutional symptoms. Of note, he was born to a mother, who is HIV-positive. However, he had three negative HIV DNA polymerase chain reaction tests at ages 0, 1, and 4 months and had received all of his prior vaccinations without complications. The child's pediatrician, a pediatric infectious disease specialist, saw the patient and felt the distribution of the rash with associated prodrome to be typical for measles. The patient was isolated and given IV fluids and antipyretics. His rash resolved over the next few days. He now remains healthy and has reverted to HIV seronegative status. A nasopharyngeal specimen was analyzed by PCR and was found to be positive for measles virus with homology to the vaccine strain. Culture for the measles virus was negative. Measles is the most contagious of the childhood exanthems. Prior to the introduction of the measles vaccine, over 130 million cases and 7 to 8 million deaths occurred worldwide each year. The WHO estimates that around 45 million cases with 1.2 million deaths still occur annually, with the majority of cases arising in less developed countries and in HIV-infected children. The first symptoms of measles occur after a 10- to 12-day incubation period that usually follows airborne or droplet exposure. The prodromal stage is heralded by fever (as high as 40.5 C), malaise, conjunctivitis, coryza, and bronchitis and lasts 2 to 4 days. Koplik stops, the exanthem believed to be pathognomic for measles, appear on the buccal mucosa 1 to 2 days before the onset of rash and may last 1 to 2 days after rash onset. An erythematous papular eruption usually appears 14 days after exposure arising on the head and spreading over the trunk to the extremities during a period of 2 to 3 days. The exanthem is most confluent on the face and upper trunk. During the next 3 to 4 days, the eruption fades. Virus can be isolated from both the nasopharynx and oral mucosa during the latter part of the incubation period and during the early stages of the exanthem. Individuals with measles are generally considered to be infectious 2 to 4 days prior to and until 3 days after the onset of the eruption. Recent experience suggests that clinical measles may be difficult to distinguish from other causes of fever and rash, such as parvovirus, enterovirus, adenovirus, or human herpes virus 6 infections. Clinical features to support the diagnosis of measles include the following: the presence of Koplik spots, the characteristic 2 to 4 days of high fever with intensifying prodromal symptoms, and the centrifugal progression of the exanthem from the head to the trunk to the extremities. Laboratory tests are necessary to confirm the diagnosis. Because of the public health importance of the disease, it is recommended that clinicians obtain a blood sample for laboratory confirmation in the US. Detection of measles-specific IgM is the most commonly used method. PCR can be used to identify measles virus RNA in urine, blood, and nasopharyngeal mucus. The Moraten vaccine, which is an attenuated live measles vaccine, is used in the US and is commonly combined with the attenuated rubella and mumps vaccine viruses. The dosing schedule is at 12 to 15 months and again between 4 and 6 years. Side effects after the live measles vaccination are generally absent or mild. Low-grade fever occurs in 5% to 15% of children and are usually on the seventh day post vaccination. Mild rash occurs in 5% and usually starts 7 to 10 days after vaccination and lasts 2 days. Serious adverse events, such as febrile seizure or anaphylaxis, occur in approximately 5.3 per 100,000 vaccinees. There are very few reports documenting an instance of typical measles proved to be caused by the vaccine strain. One concerned an HIV-infected, 1 year old boy who developed vaccine measles associated with pneumonitis. He recovered fully after 1 week. At the time of vaccination, his CD4 count was 340, and his viral load was 37,156 RNA copies/ml. It is known that children with congenital agammaglobulinemia can recover from measles, but those with deficient cell-mediated immunity tend to have life-threatening disease, pointing towards cellular immunity as being the critical determinant of severity. The American Academy of Pediatrics does not recommend giving live attenuated measles vaccine to severe immunocompromised, HIV-infected patients, but infected patients not falling into this category are advised to have the MMR vaccine in the normal two-dose regimen. Our patient was of particular concern because despite three negative DNA PCR tests, the child's HIV infection status was designated as indeterminate at the time of his presentation. Moreover, his illness was typical of wild type measles, which raised concerns about the possibility of a vaccine lot with less than the expected attenuation and the possibility of secondary spread. The first concern was resolved when the patient's HIV serologic status reverted to negative at age 15 months. The case was reported to the manufacturer and VAERS, which indicated that no similar reported cases were attributed to the vaccine lot. The patient was maintained in respiratory isolation during hospitalization and no secondary instances occurred. It is important to note that there have been no reports of transmission of vaccine associated measles virus in humans. Numerous studies have failed to isolate vaccine virus in the blood, which is thought to reflect the low level of viremia after vaccination. Therefore, it is appropriate to maintain respiratory isolation only as long as concern about the possibility for the wild virus is the issue. Additional information is not expected. A copy of the published article is attached as further documentation of the patient's experience.