CONCEPTS ON G6PD DEFICIENCY AND MALARIA

Authors

1. Solomon Awiagah; Student, Doctor of Medical Laboratory Science, University for Development Studies, Tamale, Northern Ghana. awiagahsolomon4@gmail.com
2. Mubarak Abdul-Mumeen; Student, Doctor of Medical Laboratory Science, University for Development Studies, Tamale, Northern Ghana. chempath655@gmail.com

INTRODUCTION

This article is focused on addressing some misconceptions about Glucose-6-Phosphate Dehydrogenase (G-6-PD) deficiency and malaria. The article will also elaborate on some critical findings about Laboratory G6PD investigations.

G6PD is a key enzyme in the Hexose Monophosphate Shunt or Pentose Phosphate Pathway (PPP). Reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH) is produced at the end of this metabolic pathway. This NADPH serves as a cofactor to the enzyme, Glutathione Reductase by donating its Hydrogen component. Glutathione Reductase is responsible for reducing Oxidized Glutathione (GSSG) to the active form, GSH. In its active form, GSH is a free radical scavenger. Hence there’s a reduction of oxidative stress caused by free radicals. When this pathway is defective, the amount of reduced glutathione becomes insufficient to neutralize oxidants. This leads to the denaturation of Globin which precipitates as aggregates known as Heinz bodies. Cells containing Heinz bodies are ultimately phagocytized and destroyed by the Mononuclear cells of the spleen.

The overall benefit of the pathway is that Red Blood Cells maintain their shape and do not form precipitates (Heinz bodies) so they are not destroyed before completing their 90 to 120 days lifespan. Sufficient cells will be available to transport oxygen and minimize the chance of hemolytic anemia.

Therefore reduced G6PD activity in RBCs means that sufficient NADPH would not be produced and this would impede GSSG activation. Subsequently, there would be increased oxidative stress following exposure to oxidants such as fava beans, and some drugs such as aspirin, primaquine, etc. Deleterious effects such as acute intravascular hemolysis, neonatal jaundice, and chronic hemolytic anemia (less common) could result from G6PD deficiency. Some crises could even result in serious neurological diseases. There is no alternative source of NADPH in the red cell apart from the PPP. That is why primary effects are hematologic even though G6PD deficiency affects every cell of the body. The severity of clinical symptoms depends on the variant of the G6PD gene inherited. Class I (according to WHO classification), has the most dangerous effect. It could cause chronic hemolytic anemia. It has less than 10 % residual activity.

LABORATORY INVESTIGATION

The G6PD test is done to assess the activity level of the enzyme in the individual. Because of the oxidative effects of some anti-malaria drugs, it is necessary to test for G6PD activity prior to their administration. EDTA anti-coagulated blood sample is used for the test. In severe hemolysis, samples for G6PD testing should be interpreted with caution because reticulocytes (immature red cells) have higher activity of the enzyme and may mask the deficient state in a defective individual.

DO G6PD-DEFICIENT PEOPLE GET MALARIA?

There is still a misunderstanding about G6PD-deficient people getting down with malaria. However, this should not be the case because people with G6PD Deficiency do get ill with malaria which explains why they also receive primaquine-an antimalarial and a prophylactic agent. Indeed, complete inactivation of G6PD cannot support life and the effect will be an abortion. The term deficiency is self-explanatory as it’s only a reduction, not a lack.

Therefore, the parasite could still survive even up to infective stages (trophozoite stage). It is better to say, “G6PD deficiency confers some level of protection against malaria. Deficient people mostly survive malaria”.

HOW THEN DOES THIS HAPPEN?

Understanding the role of NADPH would help answer this question. During the life cycle of the plasmodium parasite, the synthesis of several nucleotides occurs, resulting in the production of oxidative radicals. We learn from the beginning that these oxidative agents must be detoxified to prevent lysing (breakdown) of the RBCs. This is where NADPH is needed by Glutathione Reductase to form activated Glutathione for scavenging the radicals. The plasmodium parasite is an intracellular parasite and so has an erythrocytic stage occurring inside the RBCs. Destruction of the red cells means the destruction of the parasite. And that is what happens when NADPH production is reduced in G6PD deficient individuals. Enough parasitized cells could be destroyed and some level of protection is therefore provided. Therefore, it is safe to say that G6PD deficient malaria patients may not suffer the severest form of malaria because of low levels of parasitemia.

SOME CONTRAINDICATED ANTI-MALARIA DRUGS IN G6PD DEFICIENCY

Primaquine is a drug of choice for preventing malaria transmission (destroys the gametocytes of all four species of plasmodia). But this drug can cause oxidative stress and can lead to hemolytic anemia in G6PD-deficient patients. Sulphadoxine-Pyrimethamine (Intermittent Preventive treatment for Pregnant women) is also contraindicated in G6PD deficiency. Also due to its oxidative metabolites.

 

 Reference

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• Turgeon, ML, 2005, Clinical Hematology theory and procedures, 5th Ed., Lippincott Williams and Wilkins, Baltimore.
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• https://www.who.int/docs/default-source/malaria/mpac-documentation/mpac-october2019-session7-g6pd-presentation.pdf?sfvrsn=3696032c_2