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Published in: Malaria Journal 1/2013

Open Access 01-12-2013 | Research

G6PD deficiency in Plasmodium falciparum and Plasmodium vivax malaria-infected Cambodian patients

Authors: Nimol Khim, Christophe Benedet, Saorin Kim, Sim Kheng, Sovannaroth Siv, Rithea Leang, Soley Lek, Sinuon Muth, Nguon Chea, Char Meng Chuor, Socheat Duong, Alexandra Kerleguer, Pety Tor, Pheaktra Chim, Lydie Canier, Benoit Witkowski, Walter RJ Taylor, Didier Ménard

Published in: Malaria Journal | Issue 1/2013

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Abstract

Background

Glucose-6-phosphate-dehydrogenase deficiency (G6PDd) rates are unknown in malaria-infected Cambodian patients. These data are key to a rational drug policy for malaria elimination of Plasmodium falciparum and Plasmodium vivax.

Methods

From September 2010–2012, a two-year survey of G6PDd and haemoglobinopathies assessed by quantitative enzyme activity assay and haemoglobin electrophoresis, respectively, was conducted in malaria-infected patients presenting to 19 health centres throughout Cambodia.

Results

A total of 2,408 confirmed malaria patients of mean age 26.7 (range 2–81) years were recruited from mostly western Cambodia (n = 1,732, 71.9%); males outnumbered females by 3.9:1. Plasmodium falciparum was present in 1,443 (59.9%) and P. vivax in 965 (40.1%) patients. Mean G6PD activity was 11.6 (CI 95%: 11.4-11.8) U/g Hb, G6PDd was present in 13.9% of all patients (335/2,408) and severe G6PDd (including WHO Class I and II variants) was more common in western (158/1,732, 9.1%) versus eastern (21/414, 5.1%) Cambodia (P = 0.01). Of 997/2,408 (41.4%) had a haemoglobinopathy. Mean haemoglobin concentrations were inversely related to age: 8.1 g/dL < five years, 8.7 g/dL five to 14 years, and 10.4 g/dL >15 years (P <0.001).

Conclusions

G6PDd prevalence, anaemia and haemoglobinopathies were common in malaria-infected patients. The deployment of primaquine in Cambodia should be preceded by primaquine safety studies paralleled with evaluations of easy to use tests to detect G6PDd.
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Literature
1.
go back to reference Murray CJ, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, Fullman N, Naghavi M, Lozano R, Lopez AD: Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet. 2012, 379: 413-431. 10.1016/S0140-6736(12)60034-8.CrossRefPubMed Murray CJ, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, Fullman N, Naghavi M, Lozano R, Lopez AD: Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet. 2012, 379: 413-431. 10.1016/S0140-6736(12)60034-8.CrossRefPubMed
2.
go back to reference WHO: Global plan for artemisinin resistance containment (GPARC). 2011, Geneva: World Health Organization WHO: Global plan for artemisinin resistance containment (GPARC). 2011, Geneva: World Health Organization
4.
go back to reference Wells TN, Burrows JN, Baird JK: Targeting the hypnozoite reservoir of Plasmodium vivax: the hidden obstacle to malaria elimination. Trends Parasitol. 2010, 26: 145-151. 10.1016/j.pt.2009.12.005.CrossRefPubMed Wells TN, Burrows JN, Baird JK: Targeting the hypnozoite reservoir of Plasmodium vivax: the hidden obstacle to malaria elimination. Trends Parasitol. 2010, 26: 145-151. 10.1016/j.pt.2009.12.005.CrossRefPubMed
5.
go back to reference Howes RE, Battle KE, Satyagraha AW, Baird JK, Hay SI: G6PD deficiency: global distribution, genetic variants and primaquine therapy. Adv Parasitol. 2013, 81: 133-201.CrossRefPubMed Howes RE, Battle KE, Satyagraha AW, Baird JK, Hay SI: G6PD deficiency: global distribution, genetic variants and primaquine therapy. Adv Parasitol. 2013, 81: 133-201.CrossRefPubMed
6.
go back to reference Howes RE, Piel FB, Patil AP, Nyangiri OA, Gething PW, Dewi M, Hogg MM, Battle KE, Padilla CD, Baird JK: G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map. PLoS Med. 2012, 9: e1001339-10.1371/journal.pmed.1001339.PubMedCentralCrossRefPubMed Howes RE, Piel FB, Patil AP, Nyangiri OA, Gething PW, Dewi M, Hogg MM, Battle KE, Padilla CD, Baird JK: G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map. PLoS Med. 2012, 9: e1001339-10.1371/journal.pmed.1001339.PubMedCentralCrossRefPubMed
7.
go back to reference Dondorp AM, Fairhurst RM, Slutsker L, Macarthur JR, Breman JG, Guerin PJ, Wellems TE, Ringwald P, Newman RD, Plowe CV: The threat of artemisinin-resistant malaria. N Engl J Med. 2011, 365: 1073-1075. 10.1056/NEJMp1108322.PubMedCentralCrossRefPubMed Dondorp AM, Fairhurst RM, Slutsker L, Macarthur JR, Breman JG, Guerin PJ, Wellems TE, Ringwald P, Newman RD, Plowe CV: The threat of artemisinin-resistant malaria. N Engl J Med. 2011, 365: 1073-1075. 10.1056/NEJMp1108322.PubMedCentralCrossRefPubMed
8.
go back to reference World Health Organization Malaria Policy Advisory Committee and Secretariat: Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of September 2012 meeting. Malar J. 2012, 11: 424-CrossRef World Health Organization Malaria Policy Advisory Committee and Secretariat: Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of September 2012 meeting. Malar J. 2012, 11: 424-CrossRef
9.
go back to reference WHO: World Malaria Report 2012. 2012, Geneva: World Health Organization WHO: World Malaria Report 2012. 2012, Geneva: World Health Organization
10.
go back to reference World Health Organization: Glucose-6-phosphate dehydrogenase deficiency. WHO Working Group. Bull World Health Organ. 1989, 67: 601-611. World Health Organization: Glucose-6-phosphate dehydrogenase deficiency. WHO Working Group. Bull World Health Organ. 1989, 67: 601-611.
11.
go back to reference Beutler E: Glucose-6-phosphate dehydrogenase deficiency: a historical perspective. Blood. 2008, 111: 16-24. 10.1182/blood-2007-04-077412.CrossRefPubMed Beutler E: Glucose-6-phosphate dehydrogenase deficiency: a historical perspective. Blood. 2008, 111: 16-24. 10.1182/blood-2007-04-077412.CrossRefPubMed
12.
go back to reference Cappellini MD, Fiorelli G: Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008, 371: 64-74. 10.1016/S0140-6736(08)60073-2.CrossRefPubMed Cappellini MD, Fiorelli G: Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008, 371: 64-74. 10.1016/S0140-6736(08)60073-2.CrossRefPubMed
13.
go back to reference Beutler E, Yeh M, Fairbanks VF: The normal human female as a mosaic of X-chromosome activity: studies using the gene for G-6-PD-deficiency as a marker. Proc Natl Acad Sci U S A. 1962, 48: 9-16. 10.1073/pnas.48.1.9.PubMedCentralCrossRefPubMed Beutler E, Yeh M, Fairbanks VF: The normal human female as a mosaic of X-chromosome activity: studies using the gene for G-6-PD-deficiency as a marker. Proc Natl Acad Sci U S A. 1962, 48: 9-16. 10.1073/pnas.48.1.9.PubMedCentralCrossRefPubMed
14.
go back to reference Kellermeyer RW, Tarlov AR, Brewer GJ, Carson PE, Alving AS: Hemolytic effect of therapeutic drugs. Clinical considerations of the primaquine-type hemolysis. JAMA. 1962, 180: 388-394. 10.1001/jama.1962.03050180034008a.CrossRefPubMed Kellermeyer RW, Tarlov AR, Brewer GJ, Carson PE, Alving AS: Hemolytic effect of therapeutic drugs. Clinical considerations of the primaquine-type hemolysis. JAMA. 1962, 180: 388-394. 10.1001/jama.1962.03050180034008a.CrossRefPubMed
15.
go back to reference Alving AS, Carson PE, Flanagan CL, Ickes CE: Enzymatic deficiency in primaquine-sensitive erythrocytes. Science. 1956, 124: 484-485.PubMed Alving AS, Carson PE, Flanagan CL, Ickes CE: Enzymatic deficiency in primaquine-sensitive erythrocytes. Science. 1956, 124: 484-485.PubMed
16.
go back to reference Dern RJ, Beutler E, Alving AS: The hemolytic effect of primaquine V. Primaquine sensitivity as a manifestation of a multiple drug sensitivity. J Lab Clin Med. 1981, 97: 750-759.PubMed Dern RJ, Beutler E, Alving AS: The hemolytic effect of primaquine V. Primaquine sensitivity as a manifestation of a multiple drug sensitivity. J Lab Clin Med. 1981, 97: 750-759.PubMed
17.
go back to reference Shekalaghe SA, ter Braak R, Daou M, Kavishe R, van den Bijllaardt W, van den Bosch S, Koenderink JB, Luty AJ, Whitty CJ, Drakeley C, Sauerwein RW, Bousema T: In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals. Antimicrob Agents Chemother. 2010, 54: 1762-1768. 10.1128/AAC.01135-09.PubMedCentralCrossRefPubMed Shekalaghe SA, ter Braak R, Daou M, Kavishe R, van den Bijllaardt W, van den Bosch S, Koenderink JB, Luty AJ, Whitty CJ, Drakeley C, Sauerwein RW, Bousema T: In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals. Antimicrob Agents Chemother. 2010, 54: 1762-1768. 10.1128/AAC.01135-09.PubMedCentralCrossRefPubMed
18.
go back to reference Alving AS, Johnson CF, Tarlov AR, Brewer GJ, Kellermeyer RW, Carson PE: Mitigation of the haemolytic effect of primaquine and enhancement of its action against exoerythrocytic forms of the Chesson strain of Plasmodium vivax by intermittent regimens of drug administration: a preliminary report. Bull World Health Organ. 1960, 22: 621-631.PubMedCentralPubMed Alving AS, Johnson CF, Tarlov AR, Brewer GJ, Kellermeyer RW, Carson PE: Mitigation of the haemolytic effect of primaquine and enhancement of its action against exoerythrocytic forms of the Chesson strain of Plasmodium vivax by intermittent regimens of drug administration: a preliminary report. Bull World Health Organ. 1960, 22: 621-631.PubMedCentralPubMed
19.
go back to reference Buchachart K, Krudsood S, Singhasivanon P, Treeprasertsuk S, Phophak N, Srivilairit S, Chalermrut K, Rattanapong Y, Supeeranuntha L, Wilairatana P, Brittenham G, Looareesuwan S: Effect of primaquine standard dose (15 mg/day for 14 days) in the treatment of vivax malaria patients in Thailand. Southeast Asian J Trop Med Public Health. 2001, 32: 720-726.PubMed Buchachart K, Krudsood S, Singhasivanon P, Treeprasertsuk S, Phophak N, Srivilairit S, Chalermrut K, Rattanapong Y, Supeeranuntha L, Wilairatana P, Brittenham G, Looareesuwan S: Effect of primaquine standard dose (15 mg/day for 14 days) in the treatment of vivax malaria patients in Thailand. Southeast Asian J Trop Med Public Health. 2001, 32: 720-726.PubMed
20.
go back to reference Everett WD, Yoshida A, Pearlman E: Hemoglobin E and glucose-6-phosphate deficiency in the Khmer Air Force (Cambodia). Am J Trop Med Hyg. 1977, 26: 597-601.PubMed Everett WD, Yoshida A, Pearlman E: Hemoglobin E and glucose-6-phosphate deficiency in the Khmer Air Force (Cambodia). Am J Trop Med Hyg. 1977, 26: 597-601.PubMed
21.
go back to reference George JN, Sears DA, McCurdy PR, Conrad ME: Primaquine sensitivity in Caucasians: hemolytic reactions induced by primaquine in G-6-PD deficient subjects. J Lab Clin Med. 1967, 70: 80-93.PubMed George JN, Sears DA, McCurdy PR, Conrad ME: Primaquine sensitivity in Caucasians: hemolytic reactions induced by primaquine in G-6-PD deficient subjects. J Lab Clin Med. 1967, 70: 80-93.PubMed
22.
go back to reference Pannacciulli I, Salvidio E, Tizianello A, Parravidino G: Hemolytic effects of standard single dosages of primaquine and chloroquine on G-6-PD-deficient caucasians. J Lab Clin Med. 1969, 74: 653-661.PubMed Pannacciulli I, Salvidio E, Tizianello A, Parravidino G: Hemolytic effects of standard single dosages of primaquine and chloroquine on G-6-PD-deficient caucasians. J Lab Clin Med. 1969, 74: 653-661.PubMed
23.
go back to reference Goueffon S, du Saussay C: [Systematic survey on hemoglobin E and glucose-6-phosphate dehydrogenase in Cambodia (October 1965–June 1966)] (in French). Bull Soc Pathol Exot. 1969, 62: 1118-1132. Goueffon S, du Saussay C: [Systematic survey on hemoglobin E and glucose-6-phosphate dehydrogenase in Cambodia (October 1965–June 1966)] (in French). Bull Soc Pathol Exot. 1969, 62: 1118-1132.
24.
go back to reference Kim S, Nguon C, Guillard B, Duong S, Chy S, Sum S, Nhem S, Bouchier C, Tichit M, Christophel E, Taylor WR, Baird JK, Menard D: Performance of the CareStart G6PD deficiency screening test, a point-of-care diagnostic for primaquine therapy screening. PLoS One. 2011, 6: e28357-10.1371/journal.pone.0028357.PubMedCentralCrossRefPubMed Kim S, Nguon C, Guillard B, Duong S, Chy S, Sum S, Nhem S, Bouchier C, Tichit M, Christophel E, Taylor WR, Baird JK, Menard D: Performance of the CareStart G6PD deficiency screening test, a point-of-care diagnostic for primaquine therapy screening. PLoS One. 2011, 6: e28357-10.1371/journal.pone.0028357.PubMedCentralCrossRefPubMed
25.
go back to reference Louicharoen C, Nuchprayoon I: G6PD Viangchan (871G > A) is the most common G6PD-deficient variant in the Cambodian population. J Hum Genet. 2005, 50: 448-452. 10.1007/s10038-005-0276-2.CrossRefPubMed Louicharoen C, Nuchprayoon I: G6PD Viangchan (871G > A) is the most common G6PD-deficient variant in the Cambodian population. J Hum Genet. 2005, 50: 448-452. 10.1007/s10038-005-0276-2.CrossRefPubMed
26.
go back to reference Matsuoka H, Nguon C, Kanbe T, Jalloh A, Sato H, Yoshida S, Hirai M, Arai M, Socheat D, Kawamoto F: Glucose-6-phosphate dehydrogenase (G6PD) mutations in Cambodia: G6PD Viangchan (871G > A) is the most common variant in the Cambodian population. J Hum Genet. 2005, 50: 468-472. 10.1007/s10038-005-0279-z.CrossRefPubMed Matsuoka H, Nguon C, Kanbe T, Jalloh A, Sato H, Yoshida S, Hirai M, Arai M, Socheat D, Kawamoto F: Glucose-6-phosphate dehydrogenase (G6PD) mutations in Cambodia: G6PD Viangchan (871G > A) is the most common variant in the Cambodian population. J Hum Genet. 2005, 50: 468-472. 10.1007/s10038-005-0279-z.CrossRefPubMed
27.
go back to reference Monchy D, Babin FX, Srey CT, Ing PN, von Xylander S, Ly V, Busch Hallen J: [Frequency of G6PD deficiency in a group of preschool-aged children in a centrally located area of Cambodia] (in French). Med Trop (Mars). 2004, 64: 355-358. Monchy D, Babin FX, Srey CT, Ing PN, von Xylander S, Ly V, Busch Hallen J: [Frequency of G6PD deficiency in a group of preschool-aged children in a centrally located area of Cambodia] (in French). Med Trop (Mars). 2004, 64: 355-358.
28.
go back to reference Louicharoen C, Patin E, Paul R, Nuchprayoon I, Witoonpanich B, Peerapittayamongkol C, Casademont I, Sura T, Laird NM, Singhasivanon P, Quintana-Murci L, Sakuntabhai A: Positively selected G6PD-Mahidol mutation reduces Plasmodium vivax density in Southeast Asians. Science. 2009, 326: 1546-1549. 10.1126/science.1178849.CrossRefPubMed Louicharoen C, Patin E, Paul R, Nuchprayoon I, Witoonpanich B, Peerapittayamongkol C, Casademont I, Sura T, Laird NM, Singhasivanon P, Quintana-Murci L, Sakuntabhai A: Positively selected G6PD-Mahidol mutation reduces Plasmodium vivax density in Southeast Asians. Science. 2009, 326: 1546-1549. 10.1126/science.1178849.CrossRefPubMed
29.
go back to reference Hoyer S, Nguon S, Kim S, Habib N, Khim N, Sum S, Christophel EM, Bjorge S, Thomson A, Kheng S, Chea N, Yok S, Top S, Ros S, Sophal U, Thompson MM, Mellor S, Ariey F, Witkowski B, Yeang C, Yeung S, Duong S, Newman RD, Ménard D: Focused Screening and Treatment (FSAT): a PCR-based strategy to detect malaria parasite carriers and contain drug resistant P. falciparum, Pailin, Cambodia. PLoS One. 2012, 7: e45797-10.1371/journal.pone.0045797.PubMedCentralCrossRefPubMed Hoyer S, Nguon S, Kim S, Habib N, Khim N, Sum S, Christophel EM, Bjorge S, Thomson A, Kheng S, Chea N, Yok S, Top S, Ros S, Sophal U, Thompson MM, Mellor S, Ariey F, Witkowski B, Yeang C, Yeung S, Duong S, Newman RD, Ménard D: Focused Screening and Treatment (FSAT): a PCR-based strategy to detect malaria parasite carriers and contain drug resistant P. falciparum, Pailin, Cambodia. PLoS One. 2012, 7: e45797-10.1371/journal.pone.0045797.PubMedCentralCrossRefPubMed
30.
go back to reference Maude RJ, Socheat D, Nguon C, Saroth P, Dara P, Li G, Song J, Yeung S, Dondorp AM, Day NP, White NJ, White LJ: Optimising strategies for Plasmodium falciparum malaria elimination in Cambodia: primaquine, mass drug administration and artemisinin resistance. PLoS One. 2012, 7: e37166-10.1371/journal.pone.0037166.PubMedCentralCrossRefPubMed Maude RJ, Socheat D, Nguon C, Saroth P, Dara P, Li G, Song J, Yeung S, Dondorp AM, Day NP, White NJ, White LJ: Optimising strategies for Plasmodium falciparum malaria elimination in Cambodia: primaquine, mass drug administration and artemisinin resistance. PLoS One. 2012, 7: e37166-10.1371/journal.pone.0037166.PubMedCentralCrossRefPubMed
31.
go back to reference Leslie T, Mayan I, Mohammed N, Erasmus P, Kolaczinski J, Whitty CJ, Rowland M: A randomised trial of an eight-week, once weekly primaquine regimen to prevent relapse of Plasmodium vivax in Northwest Frontier Province, Pakistan. PLoS One. 2008, 3: e2861-10.1371/journal.pone.0002861.PubMedCentralCrossRefPubMed Leslie T, Mayan I, Mohammed N, Erasmus P, Kolaczinski J, Whitty CJ, Rowland M: A randomised trial of an eight-week, once weekly primaquine regimen to prevent relapse of Plasmodium vivax in Northwest Frontier Province, Pakistan. PLoS One. 2008, 3: e2861-10.1371/journal.pone.0002861.PubMedCentralCrossRefPubMed
32.
go back to reference von Seidlein L, Auburn S, Espino F, Shanks D, Cheng Q, McCarthy J, Baird K, Moyes C, Howes R, Ménard D, Bancone G, Winasti-Satyahraha A, Vestergaard LS, Green J, Domingo G, Yeung S, Price R: Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report. Malar J. 2013, 12: 112-10.1186/1475-2875-12-112.PubMedCentralCrossRefPubMed von Seidlein L, Auburn S, Espino F, Shanks D, Cheng Q, McCarthy J, Baird K, Moyes C, Howes R, Ménard D, Bancone G, Winasti-Satyahraha A, Vestergaard LS, Green J, Domingo G, Yeung S, Price R: Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report. Malar J. 2013, 12: 112-10.1186/1475-2875-12-112.PubMedCentralCrossRefPubMed
33.
go back to reference Ray RN, Chatterjea JB, Chaudhuri RN: Observations on the resistance in Hb E thalassaemia disease to induced infection with Plasmodium vivax. Bull World Health Organ. 1964, 30: 51-55.PubMedCentralPubMed Ray RN, Chatterjea JB, Chaudhuri RN: Observations on the resistance in Hb E thalassaemia disease to induced infection with Plasmodium vivax. Bull World Health Organ. 1964, 30: 51-55.PubMedCentralPubMed
Metadata
Title
G6PD deficiency in Plasmodium falciparum and Plasmodium vivax malaria-infected Cambodian patients
Authors
Nimol Khim
Christophe Benedet
Saorin Kim
Sim Kheng
Sovannaroth Siv
Rithea Leang
Soley Lek
Sinuon Muth
Nguon Chea
Char Meng Chuor
Socheat Duong
Alexandra Kerleguer
Pety Tor
Pheaktra Chim
Lydie Canier
Benoit Witkowski
Walter RJ Taylor
Didier Ménard
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2013
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-12-171

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