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
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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