A review of 2005, and a look ahead at what’s in store for 2006

December 2005

Every year, the editorial board of Infectious Diseases in Children votes on what they feel were our top headlines of the year.

Topping this list, perhaps not surprisingly, was the increasing problem of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Other issues include the licensure of several new vaccines with more on the horizon and the looming threat of an influenza pandemic.

Influenza

In recent years, the role of children in spreading influenza and the severity of this disease in the pediatric population has been rediscovered. The mortality curve rates for the very young and the very old were essentially identical in the 1918 to 1919 epidemic. That children suffer severe influenza infections may have not been fully appreciated as the infection in the very young may cause very severe croup, bronchiolitis and otitis as well as pneumonia.

There are three possible events that might result in our having a very bad influenza season.

First, there could be a significant antigenic change in the strains that have been circulating in humans for the past few years, which would result in a major epidemic. Thus far activity in the United States has been low, but this is not to say we will be spared this season. In past years epidemics have peaked after the New Year. At this time, there is no longer a need to prioritize the use of influenza vaccine according to risk. Everyone who may benefit from immunization should be vaccinated. The most immediate major threat is that there will be accelerated human-to-human transmission of the H5N1 avian strains that now have affected chickens in many new areas, including Europe. Finally, there is the possibility that a de novo strain of influenza virus will evolve directly from an avian source similar to what occurred in the 1918 to 1919 epidemic. This was a particularly virulent strain that spread readily from person to person.

Our individual efforts are focused mainly on the first problem. Namely, assuring that there is protection against the human strains that we anticipate will be prevalent during this season. It is important to remember that influenza vaccine is less effective in those younger than age 2 than in older individuals and that the close contacts of these infants also must be immunized. We also must be certain that we are immunized as well as our office and clinic staff. In addition, we should make every attempt to immunize those for whom the vaccine is indicated.

There has been much attention given to the recent reports of stockpiling osteltamivir. Of the available choices, this drug is easy to administer and is approved for children older than 1 year of age. It also is effective against influenza B strains and against the avian flu strains. Resistance has been seen less with this drug than with the M2 inhibitors, but some resistance has been noted. The government has purchased significant quantities of this drug, but will not have enough for the entire population.

Roche, the sole manufacturer and patent holder, is carefully monitoring exportation of this drug from France. Whether agreements will be reached with manufacturers in other countries or whether these manufacturers will choose to ignore patents and produce their own is unclear at this time. Sen. Charles Schumer (D-N.Y.) has made threatening noises about the United States breaking patent laws so that the drug can be manufactured domestically.

Adolescent vaccines

Perhaps the most dramatic change in immunization practice is the new emphasis on adolescent vaccination. We have had a series of recommendations for use of newly licensed vaccines in this age group. I have expressed my concern both about the absence of an infrastructure to support these programs and the emphasis given to immunization relative to the many significant health problems of this group. Parenthetically, you may want to see the movie, “The Squid and the Whale” to remind yourself of the myriad issues with which adolescents must deal. I recommend you see it yourself before deciding whether you want to send your kids off to see it.

The first vaccine to be approved for use and recommended for this age group was the quadrivalent meningococcal vaccine (Menactra, Sanofi Pasteur). Although it appears that a lot of money will be spent on preventing relatively few cases, it is difficult for one to place a price on life, especially those so young (coming from the mouth of one who is not nearly so young). But we have a good model of what has been accomplished in the United Kingdom and likely we shall see expansion of immunization against meningococcus as was done in that country.

Of some concern is that at least six of those who have been vaccinated have developed Guillian-Barré syndrome following receipt of this vaccine. It is unclear at this time whether these are causally related or the number of cases that one might expect in this population in the absence of vaccine. It is recommended, however, that one carefully weigh the risks and benefits of giving this vaccine to those with a prior history of this syndrome.

The Tdap vaccines (Boostrix, GlaxoSmithKline, and Adacel, Sanofi Pasteur) have also been approved for teenagers and there has been some noise about extending the age upward so that Tdap eventually would replace dT for routine adult immunization. We do not have a model of the Tdap strategy having worked in another country as we have for meningococcus. It will take a major effort to get enough vaccine coverage to impact infantile pertussis by producing herd immunity, prolonged cough in adults and pertussis morbidity in adolescents and adults.

We also have had the licensure of the long-awaited measles-mumps-rubella-varicella vaccine (MMRV; ProQuad, Merck), which should diminish the number of injections required during the second year of life by one. It is likely but not certain that a second dose of varicella vaccine will be given as MMRV in lieu of the second dose of MMR.

Hepatitis A vaccine has been approved down to age 12 months and may make up for the injection we have saved by combining varicella with MMRV vaccine. A decision has been made to expand the use of this vaccine from selected states to universal use. There will be a catch-up program with the details soon to be released officially.

Increasing CA-MRSA

The biggest non-vaccine story has been the increasing prevalence of MRSA. These staphylococci are resistant to all ß-lactam antibiotics. There appears to be a greater number of cases of CA-MRSA in places where it already is prevalent, reports of cases in additional areas, and some outbreaks of HA-MRSA in newborn nurseries.

The behavior of health care-associated (HA)-MRSA and CA-MRSA has been somewhat different. The latter has mainly caused superficial infections most of which respond to drainage in the case of abscesses and are usually responsive to oral agents. Clindamycin has usually been the first line choice with the caveat that inducible resistance is common and the potential for resistance should be carefully monitored. The D test is the simplest, most widely available assay for inducible resistance. Isolates also are generally sensitive to trimethoprim-sulfamethoxazole and tetracycline — the latter is an option in children 8 years of age older. Linezolid is a more expensive choice for an oral agent. However, CA-MRSA infections may be more severe, some resulting in fatal pneumonia and must be treated more aggressively.

HA-MRSA tends to be more virulent and more resistant to multiple drugs. These are more likely to produce severe systemic infections. Some very severe pneumonias have been caused by strains containing the Panton-Valentine cytotoxin. Severe infections generally require parentally administered antibiotics eg, vancomycin or quinupristin-dalfopristin. One should be aware that vancomycin resistance may be a problem and that sensitivity and serum level should be monitored. Some of these infections are sensitive to fluoroquinolones and occasionally rifampin is used in combination with the above drugs. It is well to get consultation from a pediatric infectious diseases specialist when faced with a severe staphylococcal infection.

As we look ahead to next year we probably will have vaccines against rotavirus and against human papillomavirus virus (HPV). The availability of HPV is a major achievement as at least two strains cause cervical carcinoma. HPV again will test our ability to engage our adolescent patients.

Most of all have a happy, healthy and peaceful New Year.