Predicted global prevalence of G6PD deficiency in males. Source: Howes et al 2012

Inherited Blood Disorders

Inherited blood disorders (IBDs) include all disorders that are passed down through families and affect the normal properties of blood in humans. Their clinical effects range from benign to lethal. We are interested in IBDs that are common enough to be of public health significance and particularly in those with a link to malaria.

Malaria parasites enter red blood cells during key stages of their life cycle so it is no surprise that changes to the structure or make-up of our red blood cells can have an impact on malaria infection. Some changes to red blood cells make us more resistant to malaria infection whereas others create the potential for a harmful reaction to certain antimalarial drugs. These factors add to the importance of understanding the public health burden of these disorders and our aim of providing information for public health workers involved in malaria control.

Note on the Duffy blood group: Changes to the Duffy antigen on the red blood cell do not cause a clinical disorder but they do have a large impact on resistance to malaria infection, which is why this blood group is part of our mapping work.

G6PD Deficiency

Predicted global prevalence of G6PD deficiency in males. Source: Howes et al 2012
Predicted global prevalence of G6PD deficiency in males. Source: Howes et al 2012

Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is a hereditary disease which can cause jaundice in newborn babies and haemolytic anaemia (when red blood cells break up) throughout life, usually triggered by an infection or exposure to certain foods or chemicals. One of the chemicals that can trigger severe symptoms in people with G6PD deficiency is primaquine, the only drug currently available to clear the relapsing life stages of the Plasmodium vivax parasite (one of the two major parasites causing malaria in humans) from the liver.

The gene that codes for G6PD has a number of variants; some code for normal levels of G6PD in the body, some cause mild deficiencies and some cause severe deficiencies. The gene is found on the X chromosome. Women have two copies of the X chromosome and therefore two opportunities to inherit a copy of the gene which codes for normal levels of G6PD. Men only have one copy of the X chromosome and therefore only one copy of the G6PD gene. Men are therefore more likely to suffer from severe G6PD deficiency.

G6PD deficiency can be common in populations with high levels of malaria infection caused by the parasite Plasmodium vivax. Malaria control programmes need to know this to inform their policies on using primaquine as a treatment and as a control measure for malaria in the population. Our research focuses on mapping the prevalence of G6PD deficiency and the genetic mutations causing it. We have also calculated estimates of the populations affected by the condition.

In 2012, we published a prediction of global G6PD deficiency. We have a current data gathering project to refresh our survey data on G6PD deficiency, from which a new set of global predictions will be made in due course.

Sickle Cell Disease

Predicted Global Sickle Cell Frequency. Source: Piel et al 2013
Predicted Global Sickle Cell Frequency. Source: Piel et al 2013

Sickle cell disease is by far the most common inherited blood disorder (IBD) worldwide. It is caused by a variation in the gene that codes for haemoglobin, the protein in our red blood cells that helps carry oxygen around the body. The altered protein found in people with sickle-cell disease is called haemoglobin S and occurs in people who have inherited the haemoglobin S (HbS) gene from both parents.

Individuals who have inherited the HbS gene from only one parent are carriers of the gene but usually do not have the disease itself. Carriers with just one copy of the HbS gene are more tolerant of malaria infection, making them more likely to survive the disease.

The symptoms of sickle-cell disease are serious, substantially reducing life expectancy and often requiring intensive treatment throughout the patient’s life. Sickle-cell disease is most common in Africa where expensive treatment options are often not available and resources need to be carefully targeted.

Our aim is to provide spatial intelligence on the distribution of the HbS gene so that we can provide estimates of the burden of this disorder. We have created historical and up-to-date maps showing the distribution of the HbS gene and we provide estimates of the numbers of newborns who have inherited the haemoglobin S (HbS) gene from either or both parents.

Duffy Negativity

Predicted Duffy Negativity. Source: Howes et al 2011
Predicted Duffy Negativity. Source: Howes et al 2011

The Duffy blood group is one of the many human blood groups, and Duffy blood types differ in the structure of the Duffy glycoprotein on the surface of the red blood cell. Individuals with a genetic mutation that means they do not have the Duffy glycoprotein at all, referred to as Duffy negative individuals, tend to be resistant to the Plasmodium vivax parasite (one of the two major malaria parasites). Duffy negativity is very common in sub-Saharan Africa, and rarely found in individuals outside this region.

Our work includes mapping the distribution of the common Duffy genetic variants, mapping the distribution of people who are Duffy negative and estimating the impact of Duffy negativity when we estimate the population at risk of Plasmodium vivax malaria infection.

Haemoglobin C

Predicted HbC Allele Frequency in Africa: Source Piel et al 2011
Predicted HbC Allele Frequency in Africa: Source Piel et al 2011

Haemoglobin C results from a variation in the gene that codes for haemoglobin, the protein in our red blood cells that helps carry oxygen around the body. It causes anaemia in people who have inherited the haemoglobin C (HbC) gene from both parents and can also provide a degree of protection against malaria infection.

Individuals who have inherited the HbC gene from only one parent are carriers of the gene but one copy alone does not cause anaemia. Carriers with just one copy of the HbC gene have a degree of protection against developing severe malaria.

We have created a contemporary map of distribution of the HbC gene and have used this to provide estimates of the numbers of newborns affected at various geographical scales.

Related Publications

URLDOIPiel FB., Howes RE., Nyangiri OA., Moyes CL., Williams TN., Weatherall DJ., Hay SI.,

Online biomedical resources for malaria-related red cell disorders

Human Mutation. July 2013 34(7): 937-944.
URLDOIPiel FB., Patil AP., Howes RE., Nyangiri OA., Gething PW., Dewi M., Temperley WH., Williams TN., Weatherall DJ., Hay SI.,

Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates

Lancet. January 2013 381(9861): 142-151.
URLDOIHowes RE., Piel FB., Patil AP., Nyangiri OA., Gething PW., Dewi M., Hogg MM., Battle KE., Padilla CD., Baird JK., et al,

G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map

PLoS Medicine. November 2012 9(11): e1001339.
URLDOIHowes RE., Dewi M., Piel FB., Monteiro WM., Battle KE., Messina JP., Sakuntabhai A., Satyagraha AW., Williams TN., Baird JK., et al,

Spatial distribution of G6PD deficiency variants across malaria-endemic regions

Malaria Journal. November 2013 12: 418.
URLDOIHowes RE., Battle KE., Satyagraha AW., Baird JK., Hay SI.,

G6PD deficiency: global distribution, genetic variants and primaquine therapy

Advances in Parasitology. 2013 81: 133-201.
URLDOIHowes RE., Chan ER., Rakotomanga TA., Schulte S., Gibson J., Zikursh M., Franchard T., Ramiranirina B., Ratsimbasoa A., Zimmerman PA.,

Prevalence and genetic variants of G6PD deficiency among two Malagasy populations living in Plasmodium vivax-endemic areas

Malaria Journal. April 2017 16: 139.
URLDOIHowes RE., Patil AP., Piel FB., Nyangiri OA., Kabaria CW., Gething PW., Zimmerman PA., Barnadas C., Beall CM., Gebremedhin A., et al,

The global distribution of the Duffy blood group

Nature Communications. April 2011 2: 266.
DOIKing CL., Adams JH., Xianli J., Grimberg BT., McHenry AM., Greenberg LJ., Siddiqui A., Howes RE., da Silva-Nunes M., Ferreira MU., et al,

Fy(a)/fy(b) antigen polymorphism in human erythrocyte Duffy antigen affects susceptibility to Plasmodium vivax malaria

Proceedings of the National Academy of Sciences of the United States of America. December 2011 108(50): 20113-20118.
URLDOIPiel FB., Howes RE., Patil AP., Nyangiri OA., Gething PW., Bhatt S., Williams TN., Weatherall DJ., Hay SI.,

The distribution of haemoglobin C and its prevalence in newborns in africa

Scientific Reports. April 2013 3