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Advances in Identifying Sickle Cell

Going Far, Together

Program manager Arielle Hernandez and lab manager Thad Howard examine test results from Ugandan patients.

Program Takes Expertise in Sickle Cell Treatment to Uganda, Where It Is Sorely Needed

The Laboratory: a storage space in Kampala’s central lab building, transformed in less than two weeks with equipment, supplies and manpower.

The Staff: four newly trained Ugandan employees of the Ministry of Health.

The Goal: to save tens of thousands of Ugandan children from the painful, crippling effects – and often, untimely death – caused by sickle cell disease.

It is all part of The Ugandan Sickle Surveillance Study (US3), a cooperative endeavor between Cincinnati Children’s and the Ugandan Ministry of Health. It started in February 2014 as a way to identify sickle cell in one of the areas of the world most affected by the disease, and least equipped to handle it.

“Sub-Saharan Africa is ground zero for sickle cell,” says Russell Ware, MD, PhD. “It’s where the disease originated, where the gene mutation first occurred, and where most of the patients are.”

Ware, director of the Division of Hematology at Cincinnati Children’s, has been researching sickle cell disease for 30 years. But his efforts had focused on children in the United States − a tremendously worthwhile effort, but not nearly enough. “It’s not addressing the global burden of the disease, he says. “Only 1 percent of the sickle cell patients in the world are born in North America.”

It took several trips to Africa for him to realize how little was being done in a place where the incidence of the disease was so great.

Charles Kiyaga (left), with Dr. Russell Ware, oversees the US3 study in Uganda. The program was designed to be run by the Ugandans; they process some 2,000 tests each week.

Using an Existing Network

Ware did some digging, and learned about the Early Infant Diagnosis (EID) program, begun in Uganda in 2006 by the United Nations to combat high rates of HIV infection in babies. The program established a national network that collects and tests 100,000 blood samples each year from infants born to HIV-infected mothers. Blood spots from standard heel sticks are collected on postcards, then transported from around the country for testing at the Central Public Health Laboratories in the nation’s capital, Kampala.

After analysis for HIV, the samples were thrown away. Ware wondered: why not re-purpose them? “By simply using those same cards to test for sickle cell we could get an idea of the burden and distribution of disease across the country.”

He and his team worked with Ugandan Ministry of Health officials and staff of Makerere University in Kampala to make it happen. The result is the US3 study.

Of the estimated 400,000 babies born in the world each year with sickle cell disease, 300,000 of those births occur in sub-Saharan Africa. There are African countries with higher rates of the disease, but Ware chose Uganda because it was politically stable, safe, and Ugandan officials had a growing awareness of sickle cell’s devastating effects.

Creating a Sustainable Model

Working with staff of the Ugandan Health Ministry, in under two weeks, Ware’s team converted a small storage area in the central lab in Kampala into a fully operational sickle cell testing laboratory. Cincinnati Children’s donated the equipment and testing supplies; Ware’s team helped set things up and conducted the training.

“We started from scratch,” says Arielle Hernandez, the US3 project coordinator. “They didn’t have a sickle cell lab − no capacity, no equipment or training whatsoever. It was just a storage closet.”

Hernandez and Thad Howard, Ware’s research lab manager, worked with the Ministry of Health staff to write a study protocol. They trained four Ugandans to perform the tests and run the lab.

Those technicians now process about 2,000 blood samples each week; the goal is 75,000 to 100,000 within a year. Weekly Skype meetings allow staff on both sides of the world to talk through questions and concerns. Test results are reviewed each week by a team in Uganda as well as by Howard, who says the skill and hard work demonstrated by the Ugandan technicians has been remarkable. “Nobody else is doing this in the world,” he says. “They are quickly becoming the leader in screening.”

Ware says the engagement of the Ugandans is crucial to the study’s goal of turning the tide of sickle cell disease. “When you think about studies overseas, the idea of teaching and sustainability is important. They have learned to do this quickly and well.”

Planning Ahead

After just five months, the US3 study has pinpointed four areas in Uganda where the incidence of sickle cell is highest. Ware and his team are working on next steps for when the surveillance study wraps up next February.

“We have already planned with the Health Ministry to begin a new project to screen all infants born in those four districts,” he says.

The Cincinnati Children’s sickle cell team trained Ugandan Health Ministry staff to run the sickle cell lab in Kampala.

Treatment Is Crucial – and Affordable

Once children are identified as having sickle cell, getting proper treatment to them is the essential next step, says Patrick McGann, MD, a Cincinnati Children’s hematologist who is working with Ware on another study in Africa of treatment for sickle cell.

The two hope to use US3 data to convince government officials and funding organizations of the scope of the sickle cell problem, and the difference treatment can make.

“It doesn’t take expensive medicines to make sickle cell better,” says McGann. “What these babies need are routine vaccinations and prophylactic penicillin. Those two steps will prevent a huge number of deaths. Without that, it is estimated that 50 to 80 percent of the babies will die in the first couple years of life.”

The Next Step in Treating Sickle Cell

Russell Ware, MD (left), and Patrick McGann, MD, are leading the hydroxyurea study.

The Realizing Effectiveness Across Continents with Hydroxyurea (REACH) Study hopes to bring a proven, low-cost treatment to a continent in desperate need of better outcomes for children with sickle cell disease.

Identifying children with sickle cell and providing them with routine vaccinations and penicillin helps prevent much of the mortality of sickle cell disease. But it does not change the course of the disease or prevent its painful, crippling complications. Currently the only medicine that spares children those side effects is hydroxyurea.

Russell Ware, MD, has researched the benefits of hydroxyurea for several decades. The drug boosts production of fetal hemoglobin, which protects blood cells from sickling. Typically, babies stop producing fetal hemoglobin during the first year of life.

Ware and Patrick McGann, MD, are leading the REACH study to evaluate the safety and efficacy of hydroxyurea in three African nations the Congo, Kenya and Angola. The four-year study will enroll 600 children.

The drug has proven safe even for very young children -- in fact, the NIH will revise treatment guidelines this year to include hydroxyurea as standard treatment for children with sickle cell disease.

“Our goal is to prove that hydroxyurea is possible and safe in Africa,” says McGann, “so we can help the World Health Organization and the ministries of health develop a strategy for its use.”

Transforming Lives Here at Home

Raymond Bullucks was diagnosed with sickle cell disease as a toddler. His early childhood was an odyssey of medical encounters, including frequent blood transfusions, surgery to remove his gall bladder and pain crises severe enough to require two or three hospital admissions per year.

Then at age 15, his doctors prescribed hydroxyurea, a daily medication that increases the body’s production of fetal hemoglobin. The treatment reduces sickling of red blood cells, which in turn reduces pain.

“When I was in grade school, I could get headaches from exercising too much in gym class or just being outside too long in the heat,” he says. “But in high school, I was able to get all the way through marching band camp in the middle of August without any crises.”

Although hydroxyurea treatments are far from a cure, the medication has kept his pain in control for years, says Bullucks, now 29 and an attorney in Cincinnati. He has needed hospital care only twice in the past several years.

Hydroxyurea is not a new drug, but research demonstrating its value and minimal risks for younger children is relatively recent. The latest recommendations support administering the drug to children as young as 9 months if they have three or more pain crises per year from sickle cell disease.

Sonya Moore has seen how hydroxyurea improved life for her 12-year-old daughter, Shanoah, who was diagnosed with sickle cell disease shortly after birth. “She was in the hospital about three or four times a year and on antibiotics and pain medications around the clock for two or three days at a time,” Sonya says.

At age 5, after another hospital stay to control a pain crisis, Shanoah started taking hydroxyurea. “It has been a godsend for her,” Sonya says. “Day to day, you would not know she has sickle cell. She’s bubbly, bright and active. She’s a cheerleader. She’s taking gymnastics.”

Since taking hydroxyurea, Shanoah has had far fewer hospitalizations. She has needed only five blood transfusions in her lifetime; many children her age with sickle cell require monthly blood transfusions. The key, Sonya says, is taking the medicine consistently.

“Once your child starts feeling better, she may not want to take it,” she says. “But she needs to keep on taking it so she can remain feeling better.”

National Study Proves Hydroxyurea’s Benefit

Hydroxyurea has been so successful in alleviating the painful and often life-threatening symptoms of sickle cell anemia that recently the NIH ended a national study one year early.

The study, led by Cincinnati Children’s investigators, examined the use of hydroxyurea in children with sickle cell who were at risk for stroke. Children in the study who received hydroxyurea did as well as those on chronic transfusions, with no harmful side effects. Russell Ware, MD, and Patrick McGann, MD, hope that this success will encourage more doctors to prescribe the drug’s use in pediatric patients.