Al­ter­ing vac­cine doses can save costs, lives

Daily News - - OPINION - JEF­FREY DORFMAN Dorfman is an as­so­ciate pro­fes­sor, Stel­len­bosch Univer­sity

IN 2005, be­fore most low- and mid­dle- in­come coun­tries started vac­ci­nat­ing chil­dren rou­tinely for pneu­mo­coc­cal dis­ease, it caused ap­prox­i­mately 1.5 mil­lion deaths world­wide an­nu­ally.

About 700 000 to a mil­lion of the deaths were in chil­dren un­der 5 years old. Pneu­mo­coc­cal dis­ease oc­curs when Strep­to­coc­cus pneu­mo­niae in­vades a nor­mally ster­ile area of the body, caus­ing menin­gi­tis, pneu­mo­nia, sep­ti­caemia or other dis­ease syn­dromes.

Case fatal­ity rates are high for sep­ti­caemia (> 20%) and menin­gi­tis (> 50%) in low- and mid­dle- in­come coun­tries.

Wide­spread child­hood pneu­mo­coc­cal vac­ci­na­tion re­duces death and dis­ease – even in un­vac­ci­nated in­di­vid­u­als. This is be­cause there is less cir­cu­la­tion of the bac­terium S pneu­mo­niae. The “in­di­rect” im­mu­nity is of­ten termed “herd im­mu­nity”.

The pneu­mo­coc­cal con­ju­gate vac­cine is avail­able in many coun­tries with sup­port from Gavi, the in­ter­na­tional vac­cine sup­port pro­gramme.

Gavi has sup­ported 60 low- and mid­dle- in­come coun­tries to in­tro­duce pneu­mo­coc­cal con­ju­gate vac­cines into rou­tine vac­ci­na­tion. How­ever, Gavi’s sup­port is fo­cused on the poor­est coun­tries.

More than 30 coun­tries, in­clud­ing 11 in Africa, are sched­uled to “grad­u­ate” out of di­rect Gavi sup­port when they be­come wealthy enough.

As coun­tries “grad­u­ate” from Gavi sup­port they will need to pay for the pneu­mo­coc­cal con­ju­gate vac­cine.

The pneu­mo­coc­cal con­ju­gate vac­cine sched­ule re­quires three doses. These are usu­ally the most ex­pen­sive vac­cines in child­hood im­mu­ni­sa­tion pro­grammes.

South Africa, the only African coun­try that pro­cures the vac­cines with­out fi­nan­cial as­sis­tance from Gavi, spends al­most half of its vac­cine pro­cure­ment bud­get on pneu­mo­coc­cal con­ju­gate vac­cines.

One strat­egy to re­duce the cost of vac­ci­na­tion is to re­duce the num­ber of doses re­quired per child.

We con­ducted a clin­i­cal trial to see if the dos­ing sched­ule could be safely re­duced while pre­serv­ing vac­cine ef­fi­cacy, and found that a two- dose sched­ule in­duces the same fi­nal im­mune re­sponse as a three- dose sched­ule.

Us­ing a two- dose sched­ule could re­duce vac­cine pro­gramme costs in low- and mid­dle- in­come coun­tries. Most low- and mid­dle- in­come coun­tries use a “2+ 1” vac­ci­na­tion sched­ule rec­om­mended by the World Health Or­ga­ni­za­tion.

Two pri­mary doses are ad­min­is­tered in in­fancy at six and 14 weeks of age. This is fol­lowed by one booster dose at nine months. The booster dose is needed to main­tain im­mu­nity over years. There­fore, in designing our study, we con­sid­ered drop­ping pri­mary doses and not the booster dose.

An­ti­bod­ies can pre­vent in­va­sive pneu­mo­coc­cal dis­ease. This is the ba­sis for in­di­vid­ual pro­tec­tion. An­ti­bod­ies can also pre­vent car­riage, or asymp­to­matic in­fec­tion in the na­sophar­ynx.

The level of an­ti­bod­ies needed to pre­vent car­riage is likely higher than that needed to pre­vent dis­ease. Pre­vent­ing car­riage in older chil­dren is thought to be the mech­a­nism by which the vac­cine in­duces herd im­mu­nity. This is be­cause older chil­dren are the main reser­voir of S pneu­mo­niae and car­riage is much more com­mon than dis­ease.

In our re­cent ran­domised trial, we tested two “1+ 1” sched­ules for the two cur­rently li­censed pneu­mo­coc­cal con­ju­gate vac­cines, PCV13 ( Prevnar 13) and PCV10 ( Syn­florix). We tested drop­ping ei­ther the six- week dose or the 14- week dose from the orig­i­nal three- dose sched­ule.

We found that the 1+ 1 sched­ules were not in­fe­rior to the 2+ 1 dose sched­ule in the lev­els of an­ti­bod­ies post- booster. This find­ing sug­gests that herd im­mu­nity, once in place, can be main­tained by the re­duced sched­ules.

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