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
Štítky
Interné lekárstvoČlánok vyšiel v časopise
PLOS Medicine
2010 Číslo 5
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Pleiotropní účinky statinů na kardiovaskulární systém
- Statiny indukovaná myopatie: Jak na diferenciální diagnostiku?
- DESATORO PRE PRAX: Aktuálne odporúčanie ESPEN pre nutričný manažment u pacientov s COVID-19
- Význam hydratace při hojení ran
Najčítanejšie v tomto čísle
- Self-Injurious Behavior in Adolescents
- Non-Communicable Diseases in Sub-Saharan Africa: The Case for Cohort Studies
- The Malawi Developmental Assessment Tool (MDAT): The Creation, Validation, and Reliability of a Tool to Assess Child Development in Rural African Settings
- Journals, Academics, and Pandemics