Randomized Trials Needed to Assess Benefits of Salmonella Vaccines in SCD Patients, Study Says

Randomized controlled trials are needed to examine the benefits of vaccinating people with sickle cell disease (SCD) against salmonella infections, which can be particularly fatal to children with the disease, a study says.

The review study, “Vaccines for preventing invasive salmonella infections in people with sickle cell disease,” was published in the Cochrane Database of Systematic Reviews.

Among people with SCD, mortality is highest in children, with a rate of between 2 percent and 30 percent in the first five years of life. Many of these deaths are caused by severe infections, to which children with SCD are more susceptible.

The sickle shape of SCD red blood cells makes them more prone to getting stuck inside small blood vessels, including in the spleen, which can block the blood flow through this organ and cause a condition referred to as splenic sequestration. If too severe, this condition can lead to permanent damage to the spleen and impair its ability to fight infections, particularly in children.

In addition to colds, sore throats, and ear infections, these children have a higher risk of severe invasive infections, commonly caused by pneumococcal bacteria (e.g., meningitis, sepsis, or pneumonia) or salmonella infections.

Salmonella bacteria are a common cause of foodborne illnesses but can also result in invasive and life-threatening infections such as septicemia, a serious bloodstream infection. In fact, salmonella is a common cause of septicemia in people with SCD.  These patients are also highly susceptible to another type of salmonella infection called osteomyelitis, an infection in the bone.

Management of infections secondary to SCD include preventive therapy with penicillin (a widely used group of antibiotics), vaccinations against both pneumococcus and haemophilus bacteria, and education and support for parents of affected children.

A prior review study demonstrated that vaccines against pneumococcus infection benefits people with SCD; however, although it is available in some centers, people with SCD are not routinely vaccinated against salmonella.

“It is expected that salmonella vaccines may be useful in people with sickle cell disease, especially in resource‐poor settings where the majority of those who suffer from the condition are found,” the research team wrote. 

These researchers, affiliated with the University of Calabar Teaching Hospital in Nigeria and the Medical Research Council Unit in Gambia, conducted a review study to determine whether routine administration of salmonella vaccines to SCD patients reduces the complications and deaths associated with infection.

Researchers searched the scientific literature for published randomized controlled trials that compared the use of salmonella vaccines with a placebo in people with SCD. They also looked for studies that compared the effectiveness of different types of vaccines.

Randomized controlled trials are the gold standard of clinical studies to reliably find out if a treatment is safe or effective. To be reliable and unbiased, these studies are conducted according to two major principles: The treatment undergoing testing — in this case, a vaccine — is compared with at least one control arm, either an existing treatment, a placebo, or no treatment; and subjects are randomly allocated to each study arm. 

After surveying several databases, including the World Health Organization International Clinical Trials Registry Platform and the U.S. National Library of Medicine ClinicalTrials.gov, researchers found no registries of randomized controlled trials evaluating the effect of salmonella vaccines in people with SCD.

Therefore, “there is no level of evidence on which to recommend routine use of salmonella vaccines for people with SCD” researchers wrote. The decision on whether to prescribe salmonella vaccines “is limited to the opinions of individual clinicians and to evidence presented in non‐randomized studies.”

They also stress the need for a “well‐designed, adequately‐powered, randomized controlled trial” to assess the benefits and risks of salmonella vaccines as a means of improving survival and decreasing mortality in people with SCD.