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The Impact of Phenotypic and Genotypic G6PD Deficiency on Risk of Infection: A Case-Control Study amongst Afghan Refugees in Pakistan


Background:
The most common form of malaria outside Africa, Plasmodium vivax, is more difficult to control than P. falciparum because of the latent liver hypnozoite stage, which causes multiple relapses and provides an infectious reservoir. The African (A−) G6PD (glucose-6-phosphate dehydrogenase) deficiency confers partial protection against severe P. falciparum. Recent evidence suggests that the deficiency also confers protection against P. vivax, which could explain its wide geographical distribution in human populations. The deficiency has a potentially serious interaction with antirelapse therapies (8-aminoquinolines such as primaquine). If the level of protection was sufficient, antirelapse therapy could become more widely available. We therefore tested the hypothesis that G6PD deficiency is protective against vivax malaria infection.

Methods and Findings:
A case-control study design was used amongst Afghan refugees in Pakistan. The frequency of phenotypic and genotypic G6PD deficiency in individuals with vivax malaria was compared against controls who had not had malaria in the previous two years. Phenotypic G6PD deficiency was less common amongst cases than controls (cases: 4/372 [1.1%] versus controls 42/743 [5.7%]; adjusted odds ratio [AOR] 0.18 [95% confidence interval (CI) 0.06–0.52], p = 0.001). Genetic analysis demonstrated that the G6PD deficiency allele identified (Mediterranean type) was associated with protection in hemizygous deficient males (AOR = 0.12 [95% CI 0.02–0.92], p = 0.041). The deficiency was also protective in females carrying the deficiency gene as heterozygotes or homozygotes (pooled AOR = 0.37 [95% CI 0.15–0.94], p = 0.037).

Conclusions:
G6PD deficiency (Mediterranean type) conferred significant protection against vivax malaria infection in this population whether measured by phenotype or genotype, indicating a possible evolutionary role for vivax malaria in the selective retention of the G6PD deficiency trait in human populations. Further work is required on the genotypic protection associated with other types of G6PD deficiency and on developing simple point-of-care technologies to detect it before administering antirelapse therapy.

: Please see later in the article for the Editors' Summary


Vyšlo v časopise: The Impact of Phenotypic and Genotypic G6PD Deficiency on Risk of Infection: A Case-Control Study amongst Afghan Refugees in Pakistan. PLoS Med 7(5): e32767. doi:10.1371/journal.pmed.1000283
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1000283

Souhrn

Background:
The most common form of malaria outside Africa, Plasmodium vivax, is more difficult to control than P. falciparum because of the latent liver hypnozoite stage, which causes multiple relapses and provides an infectious reservoir. The African (A−) G6PD (glucose-6-phosphate dehydrogenase) deficiency confers partial protection against severe P. falciparum. Recent evidence suggests that the deficiency also confers protection against P. vivax, which could explain its wide geographical distribution in human populations. The deficiency has a potentially serious interaction with antirelapse therapies (8-aminoquinolines such as primaquine). If the level of protection was sufficient, antirelapse therapy could become more widely available. We therefore tested the hypothesis that G6PD deficiency is protective against vivax malaria infection.

Methods and Findings:
A case-control study design was used amongst Afghan refugees in Pakistan. The frequency of phenotypic and genotypic G6PD deficiency in individuals with vivax malaria was compared against controls who had not had malaria in the previous two years. Phenotypic G6PD deficiency was less common amongst cases than controls (cases: 4/372 [1.1%] versus controls 42/743 [5.7%]; adjusted odds ratio [AOR] 0.18 [95% confidence interval (CI) 0.06–0.52], p = 0.001). Genetic analysis demonstrated that the G6PD deficiency allele identified (Mediterranean type) was associated with protection in hemizygous deficient males (AOR = 0.12 [95% CI 0.02–0.92], p = 0.041). The deficiency was also protective in females carrying the deficiency gene as heterozygotes or homozygotes (pooled AOR = 0.37 [95% CI 0.15–0.94], p = 0.037).

Conclusions:
G6PD deficiency (Mediterranean type) conferred significant protection against vivax malaria infection in this population whether measured by phenotype or genotype, indicating a possible evolutionary role for vivax malaria in the selective retention of the G6PD deficiency trait in human populations. Further work is required on the genotypic protection associated with other types of G6PD deficiency and on developing simple point-of-care technologies to detect it before administering antirelapse therapy.

: Please see later in the article for the Editors' Summary


Zdroje

1. HayC

GuerraA

TatemA

NoorR

SnowR

2005 The global distribution and population at risk of malaria: past, present, and future. Lancet Inf Dis 4 327 336 S

2. MendisK

SinaBJ

MarchesiniP

CarterR

2001 The neglected burden of Plasmodium vivax malaria. Am J Trop Med Hyg 641–2 suppl 97 106

3. KrotoskiWA

1985 Discovery of the hypnozoite and a new theory of malarial relapse. Trans R Soc Trop Med Hyg 79 1 11

4. BeutlerE

DuparcS

G6PD deficiency Working Group 2007 Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development. Am J Trop Med Hyg 77 779 789

5. NkhomaET

PooleC

VannappagariV

HallSA

BeutlerE

2009 The global prevalence of glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis. Blood Cells Mol Dis Feb 20. [Epub ahead of print]

6. Carmona-FonsecaJ

AlvarezG

MeastreA

2009 Methemoglobinemia and adverse events in plasmodium vivax malaria patients associated with high doses of primaquine therapy. Am J Trop Med Hyg 80 188 193

7. World Health Organisation 2006 Guidelines for the treatment of malaria. World Health Organisation 64

8. World Health Organisation 1989 Working group Glucose-6-phosphate dehyrogenase deficiency. Bull WHO 67 601 11

9. CappelliniMD

FiorelliG

2008 Glucose-6-phosphate dehydrogenase deficiency. Lancet 371 64 74

10. GuidoA

FairhurstRM

DoumboOK

WellemsTE

DialloDA

2007 X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria. PLoS Med 4 e66 doi:10.1371/journal.pmed.0040066

11. GillesHM

FletcherKA

HendrickseRG

LindnerR

ReddyS

1967 Glucose-6-phosphate dehydrogenase and malaria. Deficiency, sickling, and malaria in African children in South West Nigeria. Lancet 1 138 140

12. RuwendeC

KhooSC

SnowRW

1995 Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature 376 246 249

13. LouicharoenC

PatinE

PaulR

NuchprayoonI

WitoonpanichB

2009 Positively selected G6PD-Mahidol mutation reduces Plasmodium vivax density in Southeast Asians. Science 326 1546 9

14. AnsteyNM

RussellB

YeoT

PriceRN

2009 The pathophysiology of vivax malaria. Trends Parasitol 25 220 227

15. PriceRN

TjitraE

GuerraC

YeungS

WhiteNJ

2007 Vivax malaria: neglected but not benign. Am J Trop Med Hyg 77 Suppl 6 79 87

16. RowlandM

NostenF

2001 Malaria epidemiology and control in refugee camps and complex emergencies. Ann Trop Med Parasitol 95 741 754

17. RowlandM

MohammedN

RehmanH

HewittS

MendisC

2002 Anopheline vectors and malaria transmission in eastern Afghanistan. Tran R Soc Trop Med Hyg 96 620 6

18. CaroeO

1984 The Pathans: 500 B.C.-A.D. 1957. Oxford in Asia Historical Reprints. Oxford University Press

19. LeslieT

MayanI

HasanMA

SafiMH

KlinkenbergE

2007 Sulfadoxine-pyrimethamine, chlorproguanil-dapsone, or chloroquine for the treatment of Plasmodium vivax malaria in Afghanistan and Pakistan: A randomised control trial. JAMA 297 2201 9

20. LeslieT

MayanI

MohammedN

ErasmusP

KolaczinskiJ

2008 Randomised trial of an eight-week, once weekly primaquine regimen to prevent relapse of plasmodium vivax in Northwest Frontier Province, Pakistan. PLoS ONE 3 e2861 doi:10.1371/journal.pone.0002861

21. RowlandM

RabMA

FreemanT

DurraniN

RehmanN

2002 Afghan refugees and the temporal and spatial distribution of malaria in Pakistan. Soc Sci Med 55 2061 2072

22. SaundersMA

HammerMF

NachmanMW

2002 Nucleotide variability at G6pd and the signature of malarial selection in humans. Genetics 162 1849 61

23. TripathyV

ReddyNM

2007 Present status of understanding on the G6PD deficiency and natural selection. J Postgrad Med 53(3) 193 202

24. Mesbah-NaminSA

SanatiMH

MowjoodiA

Mason PJ VulliamyTJ

2002 Three major glucose-6-phosphate dehydrogenase deficient polymorphic variants identified in Mazaran state, Iran. Brit J Haematol 117 763 764

25. PetersAL

Van NoordenCJF

2009 Glucose-6-phosphate dehydrogenase deficiency and malaria: cytochemical detection of heterozygous G6PD deficient women. J Histochem Cytochem 57 1003 11

26. KwiatkowskiDP

2005 How malaria has affected the human genome and what human genetics can teach us about malaria. Am J Hum Genet 77 171 190

27. CarterR

MendisKN

2002 Evolutionary and historical aspects of the burden of malaria. Clin Microbiol Review 15(4) 565 694

28. DesaiM

ter KuileFO

NostenF

McGreadyR

2007 Epidemiology and burden of malaria in pregnancy. Lancet Inf Dis 7 93 104

29. DasA

BajajR

MohantyS

SwainV

2007 Genetic diversity and evolutionary history of Plasmodium falciparum and P. vivax. Curr Sci 92 1516 1524

30. RichSM

LeendertzFH

XuG

LeBretonM

DjokoCF

2009 The origin of malignant malaria. Proc Natl Acad Sci U S A 106 14902 7

31. JoyDA

FengX

MuJ

FuruyaT

ChotivanichK

2003 Early origin and recent expansion of Plasmodium falciparum. Science 300 318 21

32. HillDR

BairdJK

PariseME

LewisLS

RyanET

2006 Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am J Trop Med Hyg 75 402 15

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PLOS Medicine


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