In December 2008, a new pneumococcal vaccine (PCV-10) was licensed in Canada. An older vaccine (PCV-7) is used in Québec for the routine vaccination of children. The ministère de la Santé et des Services sociaux du Québec (Ministry of Health and Social Services (MSSS)) asked the Comité d'immunisation du Québec (Québec Immunization Committee (CIQ)) to rapidly give an opinion on the pertinence of this vaccine and answer the three following questions:
- Can the old and the new vaccines be considered of equivalent value in preventing invasive infections caused by the seven streptococcus pneumoniae serotypes?
- Can they be considered interchangeable in terms of primary vaccination?
- Is one or the other of the vaccines deemed to have enough benefit to justify considering only this vaccine for the next supply contract?
PCV-7 was licensed on the basis of randomized clinical trials, and a good deal of information is available on the direct and indirect effects associated with its introduction through immunization programs for North American children. PCV-10 is a new vaccine with two attractive characteristics: the presence of three additional pneumococcal polysaccharides (1, 5 and 7F) and the use of the protein D from Hi for the conjugation. PCV-10 was licensed in Canada on the basis of immunogenic data; there is currently no information on the clinical efficacy of the vaccine other than a randomized study on a precursor with a slightly different composition. The principal uncertainties surrounding PCV-10 are related to its effectiveness in practice in a schedule of three doses, and its safety in terms of rare reactions.
In the case of invasive pneumococcal infections caused by the seven serotypes that are in PCV-7-CRM197, the direct protection provided by PCV-10 should be of the same degree. The presence of three additional serotypes in PCV-10 would provide relatively modest added protection in the current Québec context: in the order of six cases of invasive infections prevented per year among children under five years of age, equivalent to about 10% of the total number of residual cases. The indirect protection that could be provided by PCV-10 needs to be assessed, because the antibody levels induced by the new product are usually lower than with the older one. The protection provided by PCV-10 against invasive infections caused by serotype 19A pneumococcus has not been determined and the same is true for rare invasive infections caused by non-encapsulated strains of Hi.
The role played by PCV-10 in preventing community-acquired pneumonia among children should be at least the same as that observed with PCV-7, and the existence of additional protection (extending eventually to empyema and infections occurring in patients suffering from chronic pulmonary disease) related to the presence of type 1 pneumococcal polysaccharide and protein D from Hi may be cited.
Non-encapsulated strains of Hi very likely play an important role in the etiology of acute bacterial otitis in Québec as everywhere else. The fact that PCV-10 induces Hi antibodies represents a definite advantage in terms of the prevention of otitis, but it is difficult to quantify the extent of this advantage with any precision given the many uncertainties related to: the distribution of otopathogenic bacteria in Canada, the protection provided by three versus four doses of PCV-10, and the replacement phenomenon that may arise with any vaccine.
The data at our disposal allow us to predict a very high safety level for PCV-10. This vaccine could be administered simultaneously with other vaccines offered in Québec during two-, four- and 12-month appointments and could also be offered to children who have already been given one or several doses of PCV-7. However, more studies are required to confirm the safety of PCV-10 and the absence of significant interference when it is administered at the same time as Pentacel.
At the same price, PCV-10 appears to be preferable to PCV-7 for the regular child immunization program in Québec. We have tried to put a figure on the price difference between the two vaccines that would tip the balance in favour of one or the other from the perspective of savings for the health system, but the estimates must be taken with much caution, given the many uncertainties existing in the parameters of the model.
The advantage of PCV-10 is especially evident for populations living in the two northern most regions of Québec and who are given four doses of pneumococcal conjugate vaccine. Otitis is very common in these populations and pneumococcus serotypes 1 and 5 are likely to cause outbreaks. PCV-10 should be offered to these populations as soon as possible.
A new 13-valent vaccine is being developed containing serotypes 19A and 7F, which are becoming more prevalent in Québec. Should this vaccine be licensed, it will be critical that a study be conducted immediately, comparing the usefulness of this new vaccine with that of PCV-7 and PCV-10 and to provide maximum flexibility in the choice of product used in Québec.