World Health Organization, 2015. Policy Brief on Single-Dose Primaquine as a Gametocytocide in Plasmodium falciparum Malaria. Geneva, Switzerland: Global Malaria Programme, World Health Organization.
von Seidlein L, Auburn S, Espino F, Shanks D, Cheng Q, McCarthy J, Baird K, Moyes C, Howes R, Ménard D, 2013. 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 12: 1.
De Niz M, Eziefula AC, Othieno L, Mbabazi E, Nabukeera D, Ssemmondo E, Gonahasa S, Tumwebaze P, DiLiberto D, Maiteki-Sebuguzi C, 2013. Tools for mass screening of G6PD deficiency: validation of the WST8/1-methoxy-PMS enzymatic assay in Uganda. Malar J 12: 1.
Ashley EA, Recht J, White NJ, 2014. Primaquine: the risks and the benefits. Malar J 13: 1186.
Luzzatto L, Nannelli C, Notaro R, 2016. Glucose-6-phosphate dehydrogenase deficiency. Hematol Oncol Clin North Am 30: 373–393.
Domingo GJ, Satyagraha AW, Anvikar A, Baird K, Bancone G, Bansil P, Carter N, Cheng Q, Culpepper J, Eziefula C, 2013. G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests. Malar J 12: 391.
World Health Organization, 2015. Guidelines for the Treatment of Malaria, 3rd edition. Geneva, Switzerland: World Health Organization.
Malaria Policy Advisory Committee Meeting, 2015. Point-of-Care G6PD Testing to Support Safe Use of Primaquine for the Treatment of Vivax Malaria. WHO Evidence Review Group Meeting Report. Geneva, Switzerland: WHO.
Pamba A, Richardson ND, Carter N, Duparc S, Premji Z, Tiono AB, Luzzatto L, 2012. Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase-deficient children receiving dapsone. Blood 120: 4123–4133.
Roh ME, Oyet C, Orikiriza P, Wade M, Kiwanuka GN, Mwanga-Amumpaire J, Parikh S, Boum Y 2nd, 2016. Asymptomatic Plasmodium infections in children in low malaria transmission setting, southwestern Uganda. Emerg Infect Dis 22: 1494–1498.
World Health Organization, 2008. Training for Mid-Level Managers (MLM): The Epi Coverage Survey. Immunizations, Vaccines, and Biologicals. Geneva, Switzerland: World Health Organization.
Johnson MK, Clark TD, Njama-Meya D, Rosenthal PJ, Parikh S, 2009. Impact of the method of G6PD deficiency assessment on genetic association studies of malaria susceptibility. PLoS One 4: e7246.
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, 2011. Performance of the CareStart G6PD deficiency screening test, a point-of-care diagnostic for primaquine therapy screening. PLoS One 6: e28357.
World Health Organization, 1989. Glucose-6-phosphate dehydrogenase deficiency. WHO working group. Bull World Health Organ 67: 601–611.
De Beaudrap P, Nabasumba C, Grandesso F, Turyakira E, Schramm B, Boum Y, Etard J-F, 2011. Heterogeneous decrease in malaria prevalence in children over a six-year period in south-western Uganda. Malar J 10: 132.
R Core Team, 2013. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Core Team.
Baird JK, Dewi M, Subekti D, Elyazar I, Satyagraha AW, 2015. Noninferiority of glucose-6-phosphate dehydrogenase deficiency diagnosis by a point-of-care rapid test vs the laboratory fluorescent spot test demonstrated by copper inhibition in normal human red blood cells. Transl Res 165: 677–688.
Okell LC, Bousema T, Griffin JT, Ouédraogo AL, Ghani AC, Drakeley CJ, 2012. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun 3: 1237.
Bwayo D, Kaddumukasa M, Ddungu H, Kironde F, 2014. Prevalence of glucose-6-phosphate dehydrogenase deficiency and its association with Plasmodium falciparum infection among children in Iganga district in Uganda. BMC Res Notes 7: 372.
Malaria Atlas Project. Population Estimates for G6PD Deficiency Table for Uganda. Available at: http://www.map.ox.ac.uk/browse-resources/g6pd/g6pdd-estimates-table/uga/. Accessed October 12, 2014.
Maiga B, Dolo A, Campino S, Sepulveda N, Corran P, Rockett KA, Troye-Blomberg M, Doumbo OK, Clark TG, 2014. Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali. Malar J 13: 270.
Shah SS, Macharia A, Makale J, Uyoga S, Kivinen K, Craik R, Hubbart C, Wellems TE, Rockett KA, Kwiatkowski DP, Williams TN, 2014. Genetic determinants of glucose-6-phosphate dehydrogenase activity in Kenya. BMC Med Genet 15: 93.
Clark TG, Fry AE, Auburn S, Campino S, Diakite M, Green A, Richardson A, Teo YY, Small K, Wilson J, Jallow M, Sisay-Joof F, Pinder M, Sabeti P, Kwiatkowski DP, Rockett KA, 2009. Allelic heterogeneity of G6PD deficiency in west Africa and severe malaria susceptibility. Eur J Hum Genet 17: 1080–1085.
Adu-Gyasi D, Asante KP, Newton S, Dosoo D, Amoako S, Adjei G, Amoako N, Ankrah L, Tchum SK, Mahama E, 2015. Evaluation of the diagnostic accuracy of CareStart G6PD deficiency rapid diagnostic test (RDT) in a malaria endemic area in Ghana, Africa. PLoS One 10: e0125796.
Satyagraha AW, Sadhewa A, Elvira R, Elyazar I, Feriandika D, Antonjaya U, Oyong D, Subekti D, Rozi IE, Domingo GJ, 2016. Assessment of point-of-care diagnostics for G6PD deficiency in malaria endemic rural eastern Indonesia. PLoS Negl Trop Dis 10: e0004457.
von Fricken ME, Weppelmann TA, Eaton WT, Masse R, de Rochars MVB, Okech BA, 2014. Performance of the CareStart glucose-6-phosphate dehydrogenase (G6PD) rapid diagnostic test in Gressier, Haiti. Am J Trop Med Hyg 91: 77–80.
Roca-Feltrer A, Khim N, Kim S, Chy S, Canier L, Kerleguer A, Tor P, Chuor CM, Kheng S, Siv S, 2014. Field trial evaluation of the performances of point-of-care tests for screening G6PD deficiency in Cambodia. PLoS One 9: e116143.
Uganda Bureau of Statistics (UBOS) and ICF International, 2010. Uganda Malaria Indicator Survey 2009. Kampala, Uganda and Rockville, MD: Uganda Malaria Surveillance Project Molecular Laboratory, National Malaria Control Programme, ICF Macro.
Uganda Bureau of Statistics (UBOS) and ICF International, 2015. Uganda Malaria Indicator Survey 2014–2015. Kampala, Uganda and Rockville, MD: Uganda Bureau of Statistics.
Bancone G, Chowwiwat N, Somsakchaicharoen R, Poodpanya L, Moo PK, Gornsawun G, Kajeechiwa L, Thwin MM, Rakthinthong S, Nosten S, 2016. Single low dose primaquine (0.25 mg/kg) does not cause clinically significant haemolysis in G6PD deficient subjects. PLoS One 11: e0151898.
Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, Anstey NM, 2007. Vivax malaria: neglected and not benign. Am J Trop Med Hyg 77: 79–87.
Eziefula AC, Gosling R, Hwang J, Hsiang MS, Bousema T, von Seidlein L, Drakeley C, 2012. Rationale for short course primaquine in Africa to interrupt malaria transmission. Malar J 11: 360.
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Abstract Views | 1038 | 745 | 53 |
Full Text Views | 632 | 12 | 3 |
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Despite the potential benefit of primaquine in reducing Plasmodium falciparum transmission and radical cure of Plasmodium vivax and Plasmodium ovale infections, concerns over risk of hemolytic toxicity in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd) have hampered its deployment. A cross-sectional survey was conducted in 2014 to assess the G6PDd prevalence among 631 children between 6 and 59 months of age in southwestern Uganda, an area where primaquine may be a promising control measure. G6PDd prevalence was determined using three detection methods: a quantitative G6PD enzyme activity assay (Trinity Biotech® G-6-PDH kit), a qualitative point-of-care test (CareStart™ G6PD rapid diagnostic test [RDT]), and molecular detection of the G6PD A− G202A allele. Qualitative tests were compared with the gold standard quantitative assay. G6PDd prevalence was higher by RDT (8.6%) than by quantitative assay (6.8%), using a < 60% activity threshold. The RDT performed optimally at a < 60% threshold and demonstrated high sensitivity (≥ 90%) and negative predictive values (100%) across three activity thresholds (below 60%, 30%, and 40%). G202A allele frequency was 6.4%, 7.9%, and 6.8% among females, males, and overall, respectively. Notably, over half of the G202A homo-/hemizygous children expressed ≥ 60% enzyme activity. Overall, the CareStart™ G6PD RDT appears to be a viable screening test to accurately identify individuals with enzyme activities below 60%. The low prevalence of G6PDd across all three diagnostic modalities and absence of severe deficiency in our study suggests that there is little barrier to the use of single-dose primaquine in this region.
Financial support: This study was supported by the Yale Downs Fellowship, Uganda Research Support Student Fund, and the Medical Education Partnership Initiative (MEPI-MESAU).
Authors' addresses: Michelle E. Roh, Martina Wade, and Sunil Parikh, Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, E-mails: mroh@gmail.com, martina.wade@yale.edu, and sunil.parikh@yale.edu. Caesar Oyet and Gertrude N. Kiwanuka, Department of Biochemistry, Mbarara University of Science and Technology, Mbarara, Uganda, E-mails: caesaroyet@yahoo.com and gekiwa2001@yahoo.co.uk. Patrick Orikiriza, Department of Microbiology, Mbarara University of Science and Technology, Mbarara, Uganda, and Médecins sans Frontières Epicentre, Mbarara Research Centre, Mbarara, Uganda, E-mail: patrick.orikiriza@epicentre.msf.org. Juliet Mwanga-Amumpaire, Department of Pediatrics, Mbarara University of Science and Technology, Mbarara, Uganda, and Médecins sans Frontières Epicentre, Mbarara Research Centre, Mbarara, Uganda, E-mail: juliet.mwanga@epicentre.msf.org. Yap Boum II, Médecins sans Frontières Epicentre, Mbarara Research Centre, Mbarara, Uganda, and Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda, E-mail: yap.boum@epicentre.msf.org.
World Health Organization, 2015. Policy Brief on Single-Dose Primaquine as a Gametocytocide in Plasmodium falciparum Malaria. Geneva, Switzerland: Global Malaria Programme, World Health Organization.
von Seidlein L, Auburn S, Espino F, Shanks D, Cheng Q, McCarthy J, Baird K, Moyes C, Howes R, Ménard D, 2013. 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 12: 1.
De Niz M, Eziefula AC, Othieno L, Mbabazi E, Nabukeera D, Ssemmondo E, Gonahasa S, Tumwebaze P, DiLiberto D, Maiteki-Sebuguzi C, 2013. Tools for mass screening of G6PD deficiency: validation of the WST8/1-methoxy-PMS enzymatic assay in Uganda. Malar J 12: 1.
Ashley EA, Recht J, White NJ, 2014. Primaquine: the risks and the benefits. Malar J 13: 1186.
Luzzatto L, Nannelli C, Notaro R, 2016. Glucose-6-phosphate dehydrogenase deficiency. Hematol Oncol Clin North Am 30: 373–393.
Domingo GJ, Satyagraha AW, Anvikar A, Baird K, Bancone G, Bansil P, Carter N, Cheng Q, Culpepper J, Eziefula C, 2013. G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests. Malar J 12: 391.
World Health Organization, 2015. Guidelines for the Treatment of Malaria, 3rd edition. Geneva, Switzerland: World Health Organization.
Malaria Policy Advisory Committee Meeting, 2015. Point-of-Care G6PD Testing to Support Safe Use of Primaquine for the Treatment of Vivax Malaria. WHO Evidence Review Group Meeting Report. Geneva, Switzerland: WHO.
Pamba A, Richardson ND, Carter N, Duparc S, Premji Z, Tiono AB, Luzzatto L, 2012. Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase-deficient children receiving dapsone. Blood 120: 4123–4133.
Roh ME, Oyet C, Orikiriza P, Wade M, Kiwanuka GN, Mwanga-Amumpaire J, Parikh S, Boum Y 2nd, 2016. Asymptomatic Plasmodium infections in children in low malaria transmission setting, southwestern Uganda. Emerg Infect Dis 22: 1494–1498.
World Health Organization, 2008. Training for Mid-Level Managers (MLM): The Epi Coverage Survey. Immunizations, Vaccines, and Biologicals. Geneva, Switzerland: World Health Organization.
Johnson MK, Clark TD, Njama-Meya D, Rosenthal PJ, Parikh S, 2009. Impact of the method of G6PD deficiency assessment on genetic association studies of malaria susceptibility. PLoS One 4: e7246.
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, 2011. Performance of the CareStart G6PD deficiency screening test, a point-of-care diagnostic for primaquine therapy screening. PLoS One 6: e28357.
World Health Organization, 1989. Glucose-6-phosphate dehydrogenase deficiency. WHO working group. Bull World Health Organ 67: 601–611.
De Beaudrap P, Nabasumba C, Grandesso F, Turyakira E, Schramm B, Boum Y, Etard J-F, 2011. Heterogeneous decrease in malaria prevalence in children over a six-year period in south-western Uganda. Malar J 10: 132.
R Core Team, 2013. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Core Team.
Baird JK, Dewi M, Subekti D, Elyazar I, Satyagraha AW, 2015. Noninferiority of glucose-6-phosphate dehydrogenase deficiency diagnosis by a point-of-care rapid test vs the laboratory fluorescent spot test demonstrated by copper inhibition in normal human red blood cells. Transl Res 165: 677–688.
Okell LC, Bousema T, Griffin JT, Ouédraogo AL, Ghani AC, Drakeley CJ, 2012. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun 3: 1237.
Bwayo D, Kaddumukasa M, Ddungu H, Kironde F, 2014. Prevalence of glucose-6-phosphate dehydrogenase deficiency and its association with Plasmodium falciparum infection among children in Iganga district in Uganda. BMC Res Notes 7: 372.
Malaria Atlas Project. Population Estimates for G6PD Deficiency Table for Uganda. Available at: http://www.map.ox.ac.uk/browse-resources/g6pd/g6pdd-estimates-table/uga/. Accessed October 12, 2014.
Maiga B, Dolo A, Campino S, Sepulveda N, Corran P, Rockett KA, Troye-Blomberg M, Doumbo OK, Clark TG, 2014. Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali. Malar J 13: 270.
Shah SS, Macharia A, Makale J, Uyoga S, Kivinen K, Craik R, Hubbart C, Wellems TE, Rockett KA, Kwiatkowski DP, Williams TN, 2014. Genetic determinants of glucose-6-phosphate dehydrogenase activity in Kenya. BMC Med Genet 15: 93.
Clark TG, Fry AE, Auburn S, Campino S, Diakite M, Green A, Richardson A, Teo YY, Small K, Wilson J, Jallow M, Sisay-Joof F, Pinder M, Sabeti P, Kwiatkowski DP, Rockett KA, 2009. Allelic heterogeneity of G6PD deficiency in west Africa and severe malaria susceptibility. Eur J Hum Genet 17: 1080–1085.
Adu-Gyasi D, Asante KP, Newton S, Dosoo D, Amoako S, Adjei G, Amoako N, Ankrah L, Tchum SK, Mahama E, 2015. Evaluation of the diagnostic accuracy of CareStart G6PD deficiency rapid diagnostic test (RDT) in a malaria endemic area in Ghana, Africa. PLoS One 10: e0125796.
Satyagraha AW, Sadhewa A, Elvira R, Elyazar I, Feriandika D, Antonjaya U, Oyong D, Subekti D, Rozi IE, Domingo GJ, 2016. Assessment of point-of-care diagnostics for G6PD deficiency in malaria endemic rural eastern Indonesia. PLoS Negl Trop Dis 10: e0004457.
von Fricken ME, Weppelmann TA, Eaton WT, Masse R, de Rochars MVB, Okech BA, 2014. Performance of the CareStart glucose-6-phosphate dehydrogenase (G6PD) rapid diagnostic test in Gressier, Haiti. Am J Trop Med Hyg 91: 77–80.
Roca-Feltrer A, Khim N, Kim S, Chy S, Canier L, Kerleguer A, Tor P, Chuor CM, Kheng S, Siv S, 2014. Field trial evaluation of the performances of point-of-care tests for screening G6PD deficiency in Cambodia. PLoS One 9: e116143.
Uganda Bureau of Statistics (UBOS) and ICF International, 2010. Uganda Malaria Indicator Survey 2009. Kampala, Uganda and Rockville, MD: Uganda Malaria Surveillance Project Molecular Laboratory, National Malaria Control Programme, ICF Macro.
Uganda Bureau of Statistics (UBOS) and ICF International, 2015. Uganda Malaria Indicator Survey 2014–2015. Kampala, Uganda and Rockville, MD: Uganda Bureau of Statistics.
Bancone G, Chowwiwat N, Somsakchaicharoen R, Poodpanya L, Moo PK, Gornsawun G, Kajeechiwa L, Thwin MM, Rakthinthong S, Nosten S, 2016. Single low dose primaquine (0.25 mg/kg) does not cause clinically significant haemolysis in G6PD deficient subjects. PLoS One 11: e0151898.
Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, Anstey NM, 2007. Vivax malaria: neglected and not benign. Am J Trop Med Hyg 77: 79–87.
Eziefula AC, Gosling R, Hwang J, Hsiang MS, Bousema T, von Seidlein L, Drakeley C, 2012. Rationale for short course primaquine in Africa to interrupt malaria transmission. Malar J 11: 360.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 1038 | 745 | 53 |
Full Text Views | 632 | 12 | 3 |
PDF Downloads | 350 | 13 | 3 |