Invasive Hib Disease Cases in Minnesota Linked to Vaccine Shortage

A nationwide shortage of Haemophilus influenzae type b, or Hib, vaccine and the refusal by some parents to vaccinate their children may have sparked a re-emergence of invasive Hib disease in Minnesota.

In the Morbidity and Mortality Weekly Report released Jan. 23, CDC officials said that five cases of invasive Hib disease in children younger than age 5 years were reported last year to the Minnesota Department of Health. Three of the five children were completely unvaccinated against the disease. One child died.

The spike in reported cases coincides with a nationwide Hib vaccine shortage that started when Merck & Co. Inc. recalled multiple lots of two of the company's products that contain Hib conjugate vaccine in mid-December 2007. Merck ceased production of those vaccines because of potential product contamination and has not yet resumed distribution.

In the interim, vaccine manufacturer sanofi pasteur has sought to fill the Hib vaccine gap with its monovalent Hib vaccine product ActHIB and another combination product.

Even so, shortly after Merck announced its recall, the CDC, in consultation with its Advisory Committee on Immunization Practices, the AAFP and the American Academy of Pediatrics, recommended that health care professionals defer the Hib booster dose except for children in certain high-risk groups.

Minnesota state epidemiologist Ruth Lynfield, M.D., said during a Jan. 23 conference call with CDC officials that the five Hib disease cases reported last year represented the state's highest total since 1992, and the death was the state's first Hib-related mortality since 1991.

Three children had received no Hib vaccine because of a parent/guardian decision to defer or outright refuse to permit vaccination, she said. A fourth child was 5 months old -- too young to have been fully immunized. A fifth child was fully vaccinated, but an immune deficiency rendered the vaccine ineffective.

Lynfield said the children lived in five different counties and had no apparent epidemiological links. None of the children attended daycare.

A Jan. 13 review of vaccination data by the Minnesota Department of Health found that among children age 7 months, Hib primary series coverage was only 46.5 percent, with 18 percent fewer children having received age-appropriate Hib vaccination compared with coverage rates for pneumococcal conjugate or diphtheria, tetanus and acellular pertussis vaccine.

Both the fallout of the vaccine shortage and parents declining vaccinations for their children are likely culprits in an overall decreased level of immunity to Hib infection, said another call participant.

"Both factors are relevant," said Kristen Ehresman, chief of the Minnesota Department of Health's Immunization Section. "The shortage could contribute to increased exposure to the bacteria in the community, but the resistance to vaccination would increase the risk of an individual child upon exposure to the disease."

Both CDC and Minnesota officials on the Jan. 23 call pointed to another possible underlying factor: the different primary dosing schedules for the two monovalent Hib vaccines -- Merck's PedvaxHIB and sanofi pasteur's ActHIB.

The ActHIB primary series consists of three doses, given at 2, 4 and 6 months of age; Merck's monovalent Hib product, PedvaxHIB, requires only two doses to complete the primary series, typically given at ages 2 and 4 months.

Anne Schuchat, M.D., director of the CDC's National Center for Immunization and Respiratory Diseases, noted that before the Hib vaccine shortage, the number of doctors nationwide who used Merck's two-dose Hib vaccine was roughly equivalent to the number who used the three-dose product manufactured by sanofi pasteur. According to Ehresman, however, a much higher percentage of Minnesota physicians had previously been using the Merck product.

Switching from Merck's two-dose primary series to Sanofi's three-dose series could be contributing to the problem if physicians and parents are unaware of the altered vaccination schedule, said Schuchat.

Schuchat said public health officials are not aware of Hib disease clusters in other states. The CDC said last December that it was stepping up its surveillance efforts for the disease.

"We really want to heighten the awareness of doctors," she said. "It's very important that they report cases to their health department so the health department can do appropriate testing to see whether there is a type b case or not."

The Jan. 23 MMWR report advises physicians who cannot obtain monovalent Hib vaccine to use an Hib-containing combination vaccine product to complete the primary series, even if it results in receipt of additional doses of other antigens.

Schuchat said that despite current production limitations, the current vaccine supply should be adequate for children to receive the recommended primary doses but not for the booster dose given at age 12-15 months.

"We're optimistic that the supply of Hib vaccine will be greatly increased by next summer, and that at that time, we'll be able to reinstitute the booster dose and call children back in for that," she added.