Mankind’s first tool to fight malaria also kills

Malaria parasites have been found in mosquitoes preserved in amber that are approximately 30 million years old. It is one of the most ancient identifiable diseases to affect humans – some suggest that malaria has killed more than any other disease in history.

Many believe that humankind’s modern fight against malaria started in 1897, when Ronald Ross discovered that malaria was transmitted by mosquitoes. And Novartis have been part of this fight against the disease, developing the gold standard antimalarial Coartem, nearly 900 million doses of which have been distributed without profit over the last two decades.

But evolution had a different answer to malaria – one that started over 7,000 years ago, with the first sickle cell mutation in the haemoglobin gene. This turns the normal red blood cells into a crescent or sickle-like shape. Malaria parasites were unable to penetrate the sickle shaped blood cells, so the mutation survived and thrived in areas where malaria was highly prevalent. People who inherited a single copy of the mutation were better protected against malaria. However, it evolved so that people who inherited the mutation from both parents will suffer from sickle cell disease.

Now up to 3% of births in some parts of Africa are of children with sickle cell disease (SCD) – nearly quarter of a million children a year. Their prospects are grim: dependent on early diagnosis and their access to healthcare, between 50-90% die before their fifth birthday.

Despite this terrible toll, the disease has a low profile on the global health agenda compared to other public health topics. This prompted Novartis to convene a SCD roundtable during the World Health Assembly in May 2018, with representatives from national governments, academic institutions, professional associations, philanthropic organizations and industry. The participants agreed that political commitment for the fight against SCD was critical in affected countries, supported by increased WHO involvement. Better diagnosis needs to be linked with comprehensive SCD care services, together with research on improving patient outcomes.

As part of this push, Novartis has signed a memorandum of understanding with the Ghanaian government to develop partnerships to screen for sickle cell disease, as well as investing in early SCD treatment.

This comes as a study published in the New England Journal of Medicine in December last year says that a simple-to-administer treatment called hydroxyurea can be safely used to treat sickle cell anemia in African children. In an unexpected twist, the trial also discovered that the children were about half as likely to get malaria while using hydroxyurea compared to a period before the start of the trial. Novartis is working to get hydroxyurea for SCD more widely available in Africa, supporting regulatory submissions in Ghana (where it has already been recently approved) and in Kenya.

As we move towards eradication of malaria in many countries over the next decades, SCD will live on as a genetic reminder of the days when the disease killed millions. Now Novartis aims to tackle that genetic inheritance as well.