Decade-Long Study Bolsters Hydroxyurea's Role As India Expands Sickle Cell Mission

As India races to identify and treat millions at risk of sickle cell disease, a rare blood disorder, under its National Sickle Cell Anaemia Elimination Mission, a decade-long study from Uganda has provided fresh evidence that continuous treatment with hydroxyurea can dramatically reduce deaths and serious complications among affected children.

The inexpensive and widely available drug is already being used in India.

The findings, published in the prestigious New England Journal of Medicine (NEJM), assume significance for India, which bears one of the world's largest burdens of sickle cell disease outside Africa and is currently undertaking one of the largest genetic disease screening programmes globally.

Researchers from Cincinnati Children's Hospital and collaborating African institutions followed children enrolled in the NOHARM trial for 10 years and found that continuous hydroxyurea treatment led to fewer painful crises, fewer hospitalisations, reduced need for blood transfusions, better growth and development, and markedly lower mortality.

"In a low-resource environment like sub-Saharan Africa, where about 50% of children with sickle cell anaemia die by the age of 10 years, we have reduced the death rate to about 1-2% per year," said Dr. Russell Ware, Director of the Division of Haematology and the Global Health Center at Cincinnati Children's and lead author of the study.

Sickle cell disease is an inherited blood disorder caused by a mutation in the haemoglobin gene. The abnormal haemoglobin causes red blood cells to become rigid and sickle-shaped, leading to blocked blood vessels, severe pain episodes, chronic anaemia, recurrent infections, stroke and progressive damage to vital organs.

In India, the disease disproportionately affects tribal communities across Madhya Pradesh, Maharashtra, Chhattisgarh, Gujarat, Odisha, Jharkhand, Telangana and several other states. Historically, delayed diagnosis and limited access to specialised care have contributed to significant illness and premature deaths.

Recognising the public health burden, the government in India launched the National Sickle Cell Anaemia Elimination Mission in 2023 with the ambitious goal of eliminating the disease as a public health challenge by 2047. The strategy focuses on mass screening, early diagnosis, genetic counselling and expanded access to treatment, including hydroxyurea.

The scale of the effort was highlighted by President of India Droupadi Murmu on Thursday during an event marking International Sickle Cell Day.

She noted that the screening target under the mission had been achieved ahead of schedule. "Around seven crore people, including newborns and individuals up to 40 years of age, have been screened under the programme," she said.

According to the president, the exercise has already identified nearly 2.5 lakh people living with sickle cell disease and more than 20 lakh carriers of the gene mutation.

The new African data, therefore, arrive at a crucial juncture for India's programme.

The hydroxyurea drug works by increasing levels of foetal haemoglobin, a naturally occurring form of haemoglobin that prevents red blood cells from assuming the damaging sickle shape.

Previous studies have shown that hydroxyurea reduces painful vaso-occlusive crises, acute chest syndrome, hospital admissions and blood transfusion requirements. However, long-term evidence extending beyond a few years has remained relatively limited, particularly in resource-constrained settings that resemble many parts of rural India.

That is what makes the Ugandan findings particularly important.

Researchers found that many children could safely tolerate higher doses—up to 30 mg/kg/day—than the fixed lower doses commonly used in earlier programmes, resulting in even better outcomes.

The African experience is also relevant because many of the obstacles faced there mirror those encountered in India. Malnutrition, infectious diseases, delayed diagnosis and limited healthcare infrastructure often complicate disease management. Yet despite these constraints, hydroxyurea delivered substantial benefits.

The Ugandan study is part of a broader body of evidence emerging from Africa, including the REACH, PIVOT, ADAPT and SPHERE trials, all of which have demonstrated the drug's effectiveness in diverse settings. These data have prompted several African countries to incorporate hydroxyurea into national treatment guidelines, while the World Health Organization now lists it as an essential medicine for sickle cell disease.

The new evidence suggests that ensuring uninterrupted access to hydroxyurea, alongside systematic follow-up and monitoring, could prove critical in translating early diagnosis into longer and healthier lives for children born with the disease.

Yet significant challenges remain.

Although hydroxyurea has transformed outcomes for many children, questions remain regarding its lifelong use. Researchers are now focusing on adolescents and young adults who began treatment in childhood. Future studies will examine long-term organ protection, fertility outcomes and any potential cancer-related risks.