Pneumococcal Vaccines Prevent Infections in Sickle Cell Disease Children: Study

Study led by MSM's Dr. Thomas Adamkiewicz, MD, finds infections are still a life-threatening risk so broader-coverage vaccines are needed.

Thomas Adamkiewicz, MDThomas Adamkiewicz, MD

Pediatric Hematologist , MSM

By Steve Bryson, PhD, Sickle Cell Disease News

Rates of life-threatening infections by pneumococcal bacteria have significantly declined, by about 80%, among children with sickle cell disease (SCD) since the introduction of pneumococcal conjugate vaccines 20 years ago.

That’s according to a study analyzing more than two decades of healthcare data from young SCD patients in metropolitan Atlanta. Results also showed that after vaccination was implemented, deaths and other severe complications of invasive pneumococcal infections (IPDs) were reduced. Such infections are potentially life-threatening, invading parts of the body that are normally free from germs.

Still, new cases of these infections in SCD children rose over 25 years, compared with those without sickle cell. Such infections pose a “life-threatening risk” to children with SCD, researchers wrote, adding that “effective vaccines with broader coverage could benefit these children.”

The study, “Pneumococcal Infections in Children with Sickle Cell Disease Before and After Pneumococcal Conjugate Vaccines,” was published in the journal Blood Advances.

Children with SCD More Susceptible to Life-Threatening Infections

Children with SCD are more susceptible to severe, life-threatening infections, including IPDs. These are caused by bacteria called Streptococcus pneumoniae, or pneumococcus.

To reduce the risk of infection-related death, SCD patients receive prophylaxis, or preventative treatment, with the penicillin antibiotic. But before its use, about 10% of SCD children under the age of 5 years developed IPD. Also, previous data suggested that IPDs accounted for 32% of all-cause mortality in SCD patients under 20 years of age.

Due to the rise in antibiotic resistance, however, researchers have adopted new methods, such as pneumococcal vaccines, to prevent infection in this vulnerable population.

“In the years 2000, as pneumococci were developing antibiotic resistance, [pneumococcal vaccines] were introduced,” Thomas Adamkiewicz, MD, the study’s first author and a pediatric hematologist at Morehouse School of Medicine in Atlanta, said in a press release. Since then, “these vaccines were developed to target bacterial serotypes [strains] not currently covered.”

To better understand changes in IPD incidence (rate of new cases) and strains among children with SCD, the research team examined 25 years of IPD surveillance data, including before and after the introduction of pneumococcal vaccines.

Results showed that 104 cases of IPD were reported during that period among 3,707 children under 10 years old with SCD or with sickle cell trait (where only one disease-causing mutation is present). This represented 6% of IPD cases in Black or African American children living in Metropolitan Atlanta (reference population).

After 2002, 87% of children with SCD received one or more doses of a pneumococcal vaccine, PCV7 or PCV13, in their first decade of life.

From 1994-1999 to 2010-2018, there was a significant decline in new cases of IPD, meningitis, and death in SCD children, up to 9 years of age. Meningitis, a common complication of IPD, refers to inflammation of the membranes covering the brain and spinal cord.

Particularly, rates of invasive pneumococcal infections dropped by 87% in children, up to 4 years old, with SCD, and by 80% in those ages 5 to 9.

Still, IPD incident rate ratios between children with SCD and the reference population increased from 20.2 to 29.2 between these time periods, indicating that the occurrence of these infections continued to increase in SCD patients.

After 2002, rates of death declined from 14% to 3% and those of meningitis dropped from 16% to 8% among children with SCD and IPD.

Regardless, after 2009, children with SCD “were 33 times more likely to develop IPD, 28 times more likely to have meningitis, and 95 times more likely to die from IPD compared to the reference population of Black or African American children,” the researchers wrote.

The team also found that penicillin resistance was more prevalent among SCD patients before PCV7’s approval in 2000.

Since the vaccine’s approval, infection rates among children with SCD, 5 years and older, decreased significantly. Moreover, since PCV13’s introduction in 2010, no IPDs caused by the strain covered by the vaccine occurred in SCD children, even though some of these children did not complete the recommended vaccine regimens.

“We examined the impact of present and potential coverage of newer vaccines,” said Adamkiewicz, who is also an adjunct professor at Emory University School of Medicine, in Atlanta.

The researchers looked at 1994-2018 data from the Georgia Emerging Infections Program that was created to identify all IPDs in Atlanta since 1994. The program is part of the Centers for Disease Control and Prevention’s Active Bacterial Core Surveillance Network.

Herd Immunity in General Population Contributed to Reduced Infection Rate

“These findings suggest that herd immunity in the general population contributed to the reduction of IPD incidence rate in SCD,” the scientists wrote.

Notably, most cases of IPD after 2000 were caused by emergent strains of pneumococcus that were not covered by the PCV7 and PVC13 vaccines.

Within three years of vaccination, the effectiveness of the older 23-valent pneumococcal polysaccharide vaccine (PPSV23) against non-PCV13 strains was 92%.

Children with SCD may benefit from receiving newly approved pneumococcal vaccines such as PCV15 and PCV20, which cover 16% and 51% of pneumococcus strains not covered by PCV13, respectively, the researchers noted.

PCV21/V116, a pneumococcal vaccine in development, may cover 92% of IPDs caused by non-PCV13 strains, the team wrote.

“One big question is the role of penicillin prophylaxis in children with SCD receiving new vaccines,” Adamkiewicz said. “We need far more data to make any recommendations.”

Overall, the results indicate that “IPD remains a persistent, life-threatening risk in children with SCD, thus underscoring the need for vaccines with broader serotype coverage and continued IPD surveillance to identify emerging targets for vaccines and other prophylactic strategies,” the researchers wrote.

Also, “while the current study is limited to one region in the United States, results may have implications for high prevalence regions of Africa for SCD,” they concluded.

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