That’s how Temaiko Odum remembers the moment she learned that the medical screening for her newborn daughter, Leah, confirmed sickle cell disease, an inherited blood disorder.
“Leah was about a week old,” Odum says. “I found out she had an illness that was not curable. What were we going to do?”
Odum immediately obtained a referral to St. Jude Children’s Research Hospital.
Symptoms of sickle cell disease include anemia, severe pain, swelling of the hands and feet, and high fevers due to weakened defenses against infections. A prime cause of those fevers is the bacteria pneumococcus.
For children like Leah, pneumococcal infections can be fatal. The bacteria can cause pneumonia, meningitis, bloodstream infections, sinusitis, middle ear infections and other illnesses. To thwart infection, antibiotics and vaccines are used regularly, but they are not always effective.
Now, a new St. Jude study helps to clarify why available vaccines for pneumococcus don’t work on some patients. The study also may guide development of more effective approaches to combat pneumococcal infections.
Targeting vulnerable kids
The first time Leah was hospitalized, she was a preschooler.
“She was very sick, in the hospital about five days,” recalls her mom. “She had a pneumococcus bacteria infection. It was scary.”
A host of bacteria live in and on the human body, for the most part causing no significant trouble. But pneumococcus finds a soft target in children with sickle cell disease.
“All of us are colonized in lots of places by bacteria,” explains Joshua Wolf, MD, of St. Jude Infectious Diseases.
Wolf works directly with patients, focusing on how pneumococcus spreads and adapts.
“Bacteria live in our skin, nose, throat, gut, mouth, eyes,” he says. “Bugs that normally live in the nose and throat almost never cause disease in normal, healthy people, but they’re able to cause serious and life-threatening infection in sickle cell patients. What the medical community has done over the past 15 years is develop lots of ways to try to prevent that by using vaccine strategies and antibiotics. But these are imperfect, and some kids die of these infections.”
Leah takes penicillin daily to prevent infection from taking hold. In spite of that precaution, she can still suffer setbacks. Infections are a constant threat.
“At St. Jude, they’re always concerned about sickle cell patients running fevers,” Odum says. “If Leah has a fever of 101 degrees or more, they want me to bring her in. Most of the time, for fever, they do blood work, see if there’s any type of infection and give her preventive antibiotics.
“Leah is now 7, and she hasn’t had any hospitalizations in almost two years.”
Cloak and daggers
Scientists have identified at least 90 types of pneumococcal bacteria, but current vaccines are effective against only 10 percent of those.
“Pneumococcus is thought to have been with mankind for thousands of years,” explains Jason Rosch, PhD, of St. Jude Infectious Diseases. “It has learned how to be transmitted and how to fight back against our immune system.”
The bacteria rapidly swap and alter DNA as a strategy to elude defenses erected by vaccines.
“Scientists have understood that this DNA exchange is occurring,” Rosch says. “We just didn’t realize how rapidly it may be occurring in some of these patients. The issue we’ve seen in recent years is that, as soon as you roll out vaccines, the bacteria swap their genetics back and forth.”
One bacterium can swap DNA with its neighbor, weakening a vaccine, or making it ineffective.
The DNA swap generally occurs when pneumococcus changes its capsule, or coat—literally, a sugar coating—making the bacteria invisible or immune to the vaccine.
Rosch and Wolf teamed with St. Jude computational biologist Robert Carter, PhD, and other colleagues to produce the first large-scale sequencing of pneumococci from children with sickle cell disease. The researchers sequenced 322 pneumococcal samples collected from sickle cell patients and 327 samples from the general public.
As they uncovered differences in the genetic code, the team discovered why pneumococcal bacteria may pose such a threat to children with sickle cell disease.
“We thought we’d see changes in the pneumococcus capsule, or coating; that’s what we were looking for,” Wolf says. “But we also found that the bacteria we obtained from children with sickle cell disease showed genetic changes in other areas of the bacterial genome.” A genome is an organism’s DNA, containing all of its genes and the instructions needed to build and sustain life.
The researchers found that in children with sickle cell disease, pneumococci had acquired mutations in genes that regulate how bacteria acquire metals, especially iron, and the way they acquire amino acids – the body’s building blocks.
“Those particular gene changes occurred in areas in which children with sickle cell disease are constitutionally different from normal kids,” Wolf says. “We think the bacteria have adapted to the special nature of children with sickle cell disease. We’re now trying to understand how this evolution of the bacteria occurs and how the bacteria adapt.”
The importance of vaccination
Even though current vaccines do not provide complete protection against pneumococcal threats, evidence shows that the inoculation benefits at-risk kids.
Vaccines force bacteria to change, and the energy needed to mutate can sap a bacteria’s ability to cause disease, explains Wolf.
“So, even though the vaccine is imperfect, it is helping to reduce the risk,” Wolf says. “That underlines the importance of making sure patients get available vaccines, as appropriate.”
Rosch says St. Jude scientists are working on vaccines designed to take better aim at specific bacterial infections affecting the general population as well as vulnerable St. Jude patients. The vaccine project takes a different approach to encouraging the immune system to protect children who are at high risk for infection.
Odum, for one, could not be more appreciative for the help St. Jude has offered her daughter. “Leah is doing well with her sickle cell disease,” Odum says. “She’s not sick a lot. She hasn’t had the fever and pain in her joints, elbow and knees that she had in the past.
“I just love the treatment she receives at St. Jude,” Odum adds.
Abridged from Promise, Autumn 2014