Responsible investigator:  Dr. sc. hum. Ari Satyagraha, Ph.D

Co-investigators:

Funded by Bill & Melinda Gates Foundation and PATH, as well as the Li KaShing Foundation, Hong Kong & Oxford, UK

 

Scientific background

 G6PD (Glucose 6 Phosphate Dehydrogenase) is one of the most common enzyme disorders in the world, affecting approximately 400 million people.  The enzyme is important in red cell metabolism by catalysing the first and rate limiting step of the pentose phosphate pathway.  There is a tremendous diversity of G6PD variants that are classified by the WHO into 5 classes based on percent residual enzyme activity and clinical manifestations.  To date, there are more than 400 G6PD variants that have been characterized.  In Indonesia, little is known on the prevalence of G6PDd variants except on several islands in the east of Indonesia. G6PD functions in the anti-oxidative pathway in the red blood cells by producing reduced NADPH which is important in the glutathione reductase pathway.  Deficiency of G6PD therefore can result in acute hemolytic anemia (AHA) when exposed to oxidative agents such as anti-malarial drug, Primaquine.

 

Because G6PD deficiency is inherited X-chromosomally, therefore, it is sometimes very difficult to distinguish heterozygous women whose activities can range from very deficient to very normal enzyme activity.  This is due to a process called X-chromosome inactivation that occur during the time in gastrulation during epiblast in which both maternal and paternal X chromosome have equal chance of being inactivated.  In terms of primaquine treatment, these heterozygous women can present some difficulties because some of their red blood cells will be inactive while the rest are normal and because of this, they can still be hemolyzed by primaquine.  However, the degree of hemolysis is unpredictable because the percentages of deficient red cells are unknown in these women.

 

Objectives

 The main aims of this study are to analyze the range of G6PD enzyme activities existing in heterozygous women having G6PD variants that are most common in Sumba and to see the percentages of deficient red cells in these women. These deficient red cells are the ones that will hemolyze upon trigger by oxidative agents such as Primaquine, an antimalarial of choice for global malaria elimination program.  The second aim is to employ a newly developed biosensor kit that can quantify G6PD activity on site and compare that with our gold standard for G6PD activity measurement from Trinity Biotech.

 

Hypothesis

 Indonesia carries one of the highest burdens of malaria in the world and G6PDd rates are thus relatively high in malaria endemic areas.  This deficiency has been shown to be ethnic/region specific. Sumba is known for its malaria meso-endemicity and Southwest Sumba (Sumba Barat Daya) district from our previous study is known to contain about 6-10% G6PD deficient individuals and thus, looking for G6PD heterozygous women in this district will not be a problem.  The range of activities in female heterozygous will range from very deficient to very normal in which the latter will contain more than 50% of normal red cells and the former will contain less than 30% normal red cells.

Potential Significance

 This study will provide information on what is the percentage of the deficient red cells in G6PD heterozygous women will react when exposed to oxidative agents as well as to inform us on the sensitivity of the available point-of-care RDT and biosensor for G6PD screening G6PD heterozygous women in the field setting.

Related unit(s):

Coordinator: Ari Winasti Satyagraha