This Nigerian hematologist established an SCD stroke prevention program in the community

September/October 2024 | Volume 23 Number 5

In this photo, Dr. Halima Bello-Manga, wearing a blue dress and headscarf, has her arms aroundtwo children, one boy wearing a red shirt with blue and white stripes and his sister, wearing a red dressand headscarf. The two children, both under age 10, are patients with sickle cell anemia.

Photo Courtesy of Halima Bello-MangaDr. Halima Bello-Manga with two children (siblings with SCA) who suffered strokes before her prevention program was established.

Sickle cell anemia (SCA) is the most severe form of sickle cell disease, an umbrella term for all disorders caused by the various sickle gene variants. Annually, more than 300,000 children worldwide are born with this inherited disease. Nigeria accounts for more than 50% of these babies.

“In my part of Nigeria, the northwestern region, SCA is the most prevalent form of sickle cell disease,” said Dr. Halima Bello-Manga, a board-certified hematologist and associate professor at Barau Dikko Teaching Hospital/Kaduna State University.

Before they reach their 20th birthday, about 11% of children with SCA will have suffered a devastating complication—stroke. As they grow older, stroke risk will increase, reaching about 24% by age 45. In 2016, Bello-Manga worked as a site investigator for a National Institutes of Health-funded clinical trial, “the primary stroke prevention in children with SCA in Nigeria (SPRING).” Later, she established a stroke prevention program for children with SCA at Barau Dikko Teaching Hospital, an academic facility affiliated with her university.

Implementing evidence-based care

More than 20 years ago, scientists found that children who are at highest risk for stroke can be identified by measuring the velocity of blood in their cerebral vessels using Transcranial Doppler (TCD) ultrasound. Simply, high velocity corresponds to high risk. “Now, we routinely test children between the ages 2 and 16 because high-risk children can benefit from an intervention,” said Bello-Manga.

In high-income nations, stroke prevention for those with high TCD velocities often begins with TCD screening and blood transfusions. In lower resource regions, blood transfusions are neither widely available nor safe, so hydroxyurea, a chemotherapy drug prescribed to manage sickle cell pain crises, is used instead. An NIH-funded clinical trial compared dosing levels of hydroxyurea for stroke prevention and found an effective lower dose, which the American Society of Hematology (ASH) also endorsed. The study also showed that twice-yearly blood tests to check for unwanted effects from this potent (and potentially toxic) drug are sufficient. Bello-Manga said, “These studies prove that it’s possible to use lower dose of hydroxyurea for stroke prevention and to administer fewer lab tests. That's a huge benefit to families because the financial burden is less.”

The three factors combined—TCD screening, hydroxyurea dosage levels, and frequency of lab testing—represent “the backbone of my project,” said Bello-Manga. She’s hoping to prove a community hospital can do as good a job as an academic hospital in correctly identifying high-risk children and managing their stroke prevention care. The rub is that academic institutions benefit from a full complement of specialists and equipment, while very few resources exist in community hospitals.

Assistance from mentors

In Nigerian academic centers, stroke prevention teams are led by physicians, TCD is performed by radiologists, and hydroxyurea is prescribed by pediatricians or hematologists. “In our community hospital, we don’t have physicians or specialists, so we had to identify the right personnel and task-shift,” said Bello-Manga. She established guidelines so that prescribing responsibilities could be transferred to medical officers and then organized workshops—with educational videos created by her advisor, Dr. Lori Jordan of Vanderbilt University—to train nurses to perform TCD.

Her reorganization of duties proved successful, but Bello-Manga has not yet completed a feasibility study (or “non-inferiority trial”) to confirm that the community site is equal to the academic site in managing stroke prevention risk. COVID-19 disrupted her progress. “I'm behind by about one year.” Still, she’s pleased with her accomplishments so far--especially the publication of several papers, including a qualitative study in Implementation Science Communications. “I’m a quantitative person, so that was a huge challenge.” She credits her mentors, Dr. Michael R. DeBaun of Vanderbilt University and Dr. Allison King of Washington University in St. Louis, who supported her work and helped with the publication. “Each time I look at the paper, I'm like, ‘Oh, wow, was I really part of that?’”

She’s also proud to have had a profound impact on many patients’ lives.

In this photo a healthcare worker, dressed in purple and blue scrubs, scans a child’s head with a probe as she conducts a Transcranial Doppler Ultrasound or TCD

Photo Courtesy of Halima Bello-MangaTranscranial Doppler Ultrasound (TCD) examination being performed by one of the nurses at the community hospital in Kaduna, Nigeria.

Translating research into policy

The SPRING trial budget had paid for the tests, drugs, and other expenses of patient-participants, but once the study ended, reality hit hard. “So you’d see a child with a high TCD velocity, but the parents tell you they don't have money to buy hydroxyurea,” said Bello-Manga. Limited options transformed the hematologist-researcher into an advocate: “We reached out to our hospital’s leadership, and they began paying for the drug.” She knew this scheme could not be sustained, given the number of children needing assistance, so she next presented her case to Kaduna’s government. “Lo and behold, the state took responsibility for providing hydroxyurea!” For her community program, children with SCA and stroke risk get hydroxyurea free of charge from the state government. Her wish is to see this replicated in all parts Nigeria and other LMICs with high burden of SCA.

As she nears completion of her project, Bello-Manga speaks with confidence about the importance of conducting sickle cell research in Nigeria. “There is nothing more interesting than observing or doing research on a certain condition in the natural space of that condition. Every patient has a different presentation and it's not what you read in books,” she said. “Our clinics are encyclopedias.”