Strain Replacement & Pathogen Evolution

Ideally, vaccines would provide perfect protection that lasts forever. However, vaccines are imperfect; they confer incomplete immunity.

Mounting evidence indicates that vaccines designed to reduce the growth rate of pathogens within their hosts produce conditions that actually increase pathogen virulence, ultimately preventing eradication of the disease.

Disease-causing organisms strive to maximally infect their hosts without killing them. Vaccines induce the targeted pathogen to adapt and evolve in unintended ways, creating undesirable disease outcomes in individuals and entire host populations.

Herd immunity may never be achieved as vaccination rates impel the pathogen family to avoid extinction by enhancing its hostile nature as it adapts to its new environment:

This evolution can erode any population-wide benefits such that overall mortality rates are unaffected, or even increase, with the level of vaccination coverage.

We find that the use of either anti-growth or anti-transmission vaccines leads to the evolution of pathogens with an increased within-host growth rate; infection of unvaccinated hosts with such evolved pathogens results in high host mortality.

The emergence and spread of mutant pathogens that evade the effects of prophylactic interventions, including vaccines, threatens our ability to control infectious diseases globally.

Vaccines that reduce pathogen replication may select for more virulent pathogens, eroding the benefits of vaccination and putting the unvaccinated at greater risk.

The control of some childhood diseases has proven to be difficult even in countries that maintain high vaccination coverage. This may be due to the use of imperfect vaccines and there has been much discussion on the different modes by which vaccines might fail.

Immunity has been shown to promote virulence:

[Vaccination] accelerated the rate of virulence evolution, rendering parasites more dangerous to naïve hosts. These results argue for further consideration of the evolutionary consequences for pathogen virulence of vaccination.

Vaccines that target some but not all strains of a disease can induce the emergence of other strains that become more prominent as they replace previous ones.

Often, the new strains are more virulent and may infect age groups normally unaffected by the disease.

Haemophilus influenzae

A vaccine targeting the “b” strain of Haemophilus influenzae was recommended for infants in 1991. Mass vaccinations against Hib increased deadly infections caused by the “a” strain and other non-b strains.

Adults and the elderly have also become more susceptible to invasive Haemophilus influenzae disease following Hib vaccinations of children:

After the introduction of Hib immunization in children, invasive Hib infections in unimmunized adults also declined, but the overall rate of invasive Hi disease in adults increased.

Specifically, deadly infections from Haemophilus influenzae type “a” have increased, turning it into a “major invasive bacterial disease.”

In addition, the incidence of Hia meningitis increased 8-fold within one year after a vaccination program against Hib was initiated.

Several of the new strains are severe. More than one-third of Hif cases and one-fifth of the non-typeable cases require intensive care:

The clinical burden of invasive non-type “b” H. influenzae disease, measured as days of hospitalization/100,000 individuals at risk and year, increased significantly throughout the study period.

Vaccination against Hib has altered the epidemiology of invasive Haemophilus influenzae infections. Prior to infant vaccination against Hib, 65% of all Haemophilus influenzae cases were caused by the “b” strain. Now, 84% of all cases are now caused by the “f” strain and other non-b strains.

Since the introduction of the Hib vaccine, there have been more fatal cases of non-Hib infections in the elderly:

The epidemiological characteristics of invasive H. influenzae disease have changed from a disease that predominantly affects children and is dominated by type b to a disease that predominantly affects adults and is dominated by non-typeable strains.

The increased cases of virulent non-b Haemophilus influenzae among adults could be caused by the loss of cross-immunity that was provided by natural exposure to Hib or from changes in the organisms.

Invasive non-b strains of Haemophilus influenzae are more virulent, causing severe disease in the pediatric population. These non-typeable strains are resistant to antibiotics.

Pneumococcal disease

The Streptococcus pneumoniae pathogen has more than 90 different strains. In 2000, a vaccine that targeted 7 of these strains was recommended for infants. In 2010, a new vaccine was introduced that targeted 13 pneumococcal strains.

Pneumococcal disease rates initially declined following the vaccine's release, but then increased when non-vaccine strains quickly replaced strains targeted by the vaccine. Many of these new strains are highly virulent and resistant to antibiotics.

Pneumococcal vaccination of children also significantly increased the risk of the disease in adults. Vaccine-induced pneumococcal strains are now a worldwide problem, posing a threat to the long-term effectiveness of pneumococcal vaccination.

Cases of invasive pneumococcal disease in adults have increased significantly:

Gains in disease reduction were offset by increases in replacement serotypes, particularly among the over-65 age group.

Although the vaccine was effective against some strains, “the emergence of replacement nonvaccine pneumococcal serotypes has resulted in an increase in the incidence of serious and invasive infections.”

The increase in carriage of non-vaccine serotypes, and the consequent increase in invasive disease, could reduce, negate or outweigh the benefit.

Adults are especially at risk of invasive pneumococcal disease caused by vaccine-induced replacement serotypes, but infants have been affected as well.

There is evidence that antibiotic-resistant strains of invasive pneumococcal disease have arisen from recombinations of vaccine and non-vaccine strains.

Due to strain replacement, the overall pneumococcal rate hasn't changed. Also, the new vaccine that targets 13 strains “did not affect the rate of overall pneumococcal colonization.”

The pneumococcal conjugate vaccines (PCVs) that are currently in use only protect against some serotypes of the bacterium, and there is now strong evidence that those serotypes not included in the vaccine increase in prevalence among most vaccinated populations.

Just two years after PCV13 was introduced, 94% of all pneumococcal strains in healthy children were non-vaccine targeted serotypes. PCV13 is expected to induce strain replacement like that seen with PCV7.

Strain replacement is inevitable when vaccines only target some of the many strains that are in competition with each other.

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