Impact of malarial infection in G6PD deficient patient in malarial infection

1. G6PD Deficiency and malaria
Presented by:
Mohammad Adeel Zafar
M.S. (Pharm.)
Department of Pharmacology and Toxicology
National Institute Of Pharmaceutical Education and Research
S.A.S Nagar, sec- 67, Mohali ,Punjab – 160062
INDIA

2. Flow of presentation
▪ Introduction
▪ Etiology of Malaria
▪ Life cycle
▪ Disease burden
▪ G6PD
▪ G6PD Deficiency and Malaria
▪ Detection of G6PD
▪ Conclusion

3. Malaria
• The term malaria comes from 'mal' 'aria', or bad air
• Malria is the oldest known parasitic desease
• 40% of the world population is at risk of malaria
• The Disease is widespread in the tropical regions like
sub-saharan Africa, Asia and Latin America

4. Introduction
• Malaria is a vector-borne infectious disease caused by
single-celled protozoan parasites of the genus
plasmodium
• Female anopheles is the vector of this disease
• The parasite feeds off of red blood cell contents ,
causing the red blood cells to eventually burst

5. Etiology of Malaria
• Following species are known to infect humans
➢ Plasmodium vivax
➢ Plasmodium malariae
➢ Plasmodium ovale
➢ Plasmodium falciparum
➢ Plasmodium knowlesi (forested regions of south east asia)

6. Transmission
• Malaria is transmitted through following methods
➢ Blood transfusion
➢ Transplantation
➢ Infected needles
➢ From mother to fetus during pregnancy
(Slinger et al., 2001, Swenerton et al., 2009, Gitau et al., 2005)

7. Life Cycle

8. Stages of Malarial life cycle
• Pre - erythrocytic stage
• Erythrocytic stage
• Gametocyte
• Exoerythrocytic stage

9. Disease Burden
• According to latest WHO estimates, there were 214
million cases of malaria and 438000 deaths between
2000 and 2015
• Mainly in sub-saharan Africa account for 80% of
malaria cases and 78% deaths globally
http://www.who.int/mediacentre/factsheets/fs094/en/

10. Glucose-6-Phosphate Dehydrogenase
• G6PD is a cytosolic enzyme which is involved in
pentose phosphate pathway
• It protect the red blood cells from the effects of
potentially harmful Reactive Oxygen Species

11. Genetics of G6PD
• It is present on the q28 locus of the X-chromosome

12. Enzymology of G6PD
• G6PD is a monomer of 515 Amino Acid
• It has a molecular mass of over 59 kDa
• G6PD catalyses and control the oxidative pentose
phosphate pathway
• NADP+
acts as a substrate for activation of enzyme

13. G6PD in erythrocytes
• During aging of erythrocyte , the quantity of active G6PD decreases,
and older erythrocyte become vulnerable to oxidative stress
• The severity of G6PD deficiency is usually measured in 4 classes :-
➢ CLASS I : Severe (Less than 10% of normal G6PD
function)
➢ CLASS II : Intermediate (10% or more )
➢ CLASS III : Mild (Upto 60% )
➢ CLASS IV : Asymptomatic (60 – 100 %)

14. Malaria and G6PD deficiency
• 50% reduction in severe malaria was found in G6PD
deficient African children
• In female hetrozygotes there are more malarial parasite in
G6PD replete cells compared to G6PD deficient cells
• Invasion appears to be similar but growth is retarded in
G6PD deficient cells
• Possible mechanism is oxidant stress leading to cell death
or membrane damage leading to phagocytosis

15. Continued.....
• Acute and chronic malaria can cause anemia
• In severe G6PD deficient patient treatment with
primaquine and dapsone can lead to life threatening
acute intravascular hemolysis followed by anemia and
acute renal failure

16. Prevalence of G6PD Deficiency
• Worldwide, 300–400 million people carry at least one deficient
G6PD
• The frequency of mutations varies greatly among different
populations
• G6PD A- is the most prevalent mutation in Africans and Afro-
Americans
gene (World Health Organization 1989; Nkhoma et al. 2009)

17. Detection of G6PD Deficiency
• Following tests are used to detect G6PD deficiency
➢ Fluorescent spot test
➢ spectrophotometric assay
➢ cytochemical assay
(Beutler, 1984, Vogels et al., 1986, Van Noorden et al., 1982).

18. Conclusion
• G6PD deficiency causes problems primarily when the
deficiency is complicated by the treatment of malaria
• Treatment can cause (severe) hemolysis in G6PDdeficient
patients
• Patients should be screened for G6PD deficiency before
treatment with these potential hemolytic agents