ASH Clinical News ACN_5.1_Digital - Page 30

Blood Beyond Borders Our newest series looks at blood disorders through a global lens, from international trends in disease treatment to innovative initiatives in developing countries. Malaria and Thalassemia in the Mediterranean Basin In 1949, British scientist John Burdon Sanderson Haldane made a novel connection between red cell disorders and malaria: The genetic mutations that lead to several types of anemias, including thal- assemia and sickle cell anemia, have persisted in certain human populations where malaria was his- torically endemic because individuals heterozygous for these mutations have some type of advantage against the bloodborne infectious disease. 1 Red cell disorders and malaria, Haldane ob- served, were prevalent among people living in warm climates of European, North African, and West Asian countries that surround the Mediterranean Sea (collectively called the Mediterranean Basin). “Haldane was working on anemias in the Mediterranean in the 1940s, but he didn’t know for sure that these were thalassemias at the time,” Thomas N. Williams, FMedSci, professor in the department of medicine at the Imperial College and St. Mary’s Hospital in London, told ASH Clinical News. Dr. Williams conducts research on hematologic disorders, including on mechanisms of malaria resistance in children with red cell dis- orders at the KEMRI-Wellcome Trust Research Programme in Kilifi, Kenya. “The molecular biology of thalassemia had not yet been worked out. That happened only about 20 years later,” he continued. “Dr. Haldane knew that this was an inherited disorder only because it ran in families. When he saw that thalassemia was much more prevalent where malaria also was pres- ent, he came to the hypothesis that the mutations in these families likely persisted because it offered 28 ASH Clinical News some protection against malaria in these malaria- endemic geographies.” Based on his observations, Haldane theorized that “because the red blood cells were small in those with certain types of anemias, the malaria parasite had a harder time getting into and thriv- ing inside these cells,” Dr. Williams explained. “He was ahead of his time in his ability to put these two complicated diseases together.” For this first edition of “Blood Beyond Borders,” ASH Clinical News spoke with Dr. Williams and other thalassemia specialists about the history and prevalence of the diseases in the Mediterranean re- gion and the burden to patients and health systems. Two Seemingly Unrelated Diseases The term thalassemia derives from the Greek name “Thalassa,” which in Greek mythology represented the spirit of the sea. Even though thalassemias are found in people around the world, the name was coined because many of the first cases of thalassemia were observed in the Mediterranean Basin, with fami- lies passing the mutations down through generations. The hereditary hemoglobinopathy involves alterations in the globin chains that make up the hemoglobin molecule. The disease is classified as either alpha or beta thalassemia depending on whether the alpha or beta hemoglobin chain harbors a mutation. Four genes (two from each parent) are needed to make enough alpha or beta globin protein chains; alpha or beta thalassemia trait occurs if one or two of the four genes are missing or altered. The severity of thalassemia depends on how many of these genes are affected – the higher the number, the higher the symptom burden. 2 Malaria is an ancient, mosquito-borne disease that, according to a recent DNA analysis of 2,000-year-old remains in Sardinia, has been present in the Mediterranean Basin by the Roman period. 3 Several factors contribute to the prevalence of malaria in these areas: Female Anopheles mosquitoes infected with the Plasmodium parasite that causes malaria lay their eggs in shallow, still, fresh water such as puddles and hoof prints – both of which are abundant throughout tropical countries during rainy seasons. Malaria transmission also is more frequent in areas where the warm and wet weather season is longer, resulting in a longer mosquito lifespan. Despite substantial global progress to curb and eliminate malaria, the disease is still a substantial public health problem around the world. The National Institute of Allergy and Infectious Disease reports that approximately 3.2 billion people worldwide are at risk for the disease. Similarly, the World Health Organization estimates that about half of the world’s population is at risk. As of 2017, 90 countries and regions reported cases of malaria transmission. 4 Many countries in the Mediterranean, includ- ing Greece, had eradicated malaria by the late 1970s but saw an uptick in the number of imported cases as a result of increased international travel, climate changes, and the movement of immigrants from malaria-endemic countries. 5 January 2019