The tolerability of single low dose primaquine in glucose-6-phosphate deficient and normal falciparum-infected Cambodians
Abstract Background The WHO recommends single low-dose primaquine (SLDPQ, 0.25 mg/kg body weight) in falciparum-infected patients to block malaria transmission and contribute to eliminating multidrug resistant Plasmodium falciparum from the Greater Mekong Sub region (GMS). However, the anxiety regar...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | http://link.springer.com/article/10.1186/s12879-019-3862-1 |
| _version_ | 1818112652663062528 |
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| author | Lek Dysoley Saorin Kim Sergio Lopes Nimol Khim Steven Bjorges Samphornarann Top Chea Huch Huy Rekol Nelli Westercamp Mark M. Fukuda Jimee Hwang Arantxa Roca-Feltrer Mavuto Mukaka Didier Menard Walter R. Taylor |
| author_facet | Lek Dysoley Saorin Kim Sergio Lopes Nimol Khim Steven Bjorges Samphornarann Top Chea Huch Huy Rekol Nelli Westercamp Mark M. Fukuda Jimee Hwang Arantxa Roca-Feltrer Mavuto Mukaka Didier Menard Walter R. Taylor |
| author_sort | Lek Dysoley |
| collection | DOAJ |
| description | Abstract Background The WHO recommends single low-dose primaquine (SLDPQ, 0.25 mg/kg body weight) in falciparum-infected patients to block malaria transmission and contribute to eliminating multidrug resistant Plasmodium falciparum from the Greater Mekong Sub region (GMS). However, the anxiety regarding PQ-induced acute haemolytic anaemia in glucose-6-phosphate dehydrogenase deficiency (G6PDd) has hindered its use. Therefore, we assessed the tolerability of SLDPQ in Cambodia to inform national policy. Methods This open randomised trial of dihydroartemisinin-piperaquine (DHAPP) + SLDPQ vs. DHAPP alone recruited Cambodians aged ≥1 year with acute uncomplicated P. falciparum. Randomisation was 4:1 DHAPP+SLDPQ: DHAPP for G6PDd patients and 1:1 for G6PDn patients, according to the results of the qualitative fluorescent spot test. Definitive G6PD status was determined by genotyping. Day (D) 7 haemoglobin (Hb) concentration was the primary outcome measure. Results One hundred nine patients (88 males, 21 females), aged 4–76 years (median 23) were enrolled; 12 were G6PDd Viangchan (9 hemizygous males, 3 heterozygous females). Mean nadir Hb occurred on D7 [11.6 (range 6.4 ─ 15.6) g/dL] and was significantly lower (p = 0.040) in G6PDd (n = 9) vs. G6PDn (n = 46) DHAPP+SLDPQ recipients: 10.9 vs. 12.05 g/dL, Δ = -1.15 (95% CI: -2.24 ─ -0.05) g/dL. Three G6PDn patients had D7 Hb concentrations < 8 g/dL; D7-D0 Hbs were 6.4 ─ 6.9, 7.4 ─ 7.4, and 7.5 ─ 8.2 g/dL. For all patients, mean (range) D7-D0 Hb decline was -1.45 (-4.8 ─ 2.4) g/dL, associated significantly with higher D0 Hb, higher D0 parasitaemia, and receiving DHAPP; G6PDd was not a factor. No patient required a blood transfusion. Conclusions DHAPP+SLDPQ was associated with modest Hb declines in G6PD Viangchan, a moderately severe variant. Our data augment growing evidence that SLDPQ in SE Asia is well tolerated and appears safe in G6PDd patients. Cambodia is now deploying SLDPQ and this should encourage other GMS countries to follow suit. Trial registration The clinicaltrials.gov reference number is NCT02434952. |
| first_indexed | 2024-12-11T03:22:21Z |
| format | Article |
| id | doaj.art-f43d29e65bdd4344b9eb9d7fa6183f62 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-11T03:22:21Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-f43d29e65bdd4344b9eb9d7fa6183f622022-12-22T01:22:36ZengBMCBMC Infectious Diseases1471-23342019-03-0119111110.1186/s12879-019-3862-1The tolerability of single low dose primaquine in glucose-6-phosphate deficient and normal falciparum-infected CambodiansLek Dysoley0Saorin Kim1Sergio Lopes2Nimol Khim3Steven Bjorges4Samphornarann Top5Chea Huch6Huy Rekol7Nelli Westercamp8Mark M. Fukuda9Jimee Hwang10Arantxa Roca-Feltrer11Mavuto Mukaka12Didier Menard13Walter R. Taylor14National Center for National Centre for Parasitology, Entomology and Malaria ControlInstitut Pasteur du CambodgeMalaria ConsortiumInstitut Pasteur du CambodgeWHO Cambodia country officeWHO Cambodia country officeNational Center for National Centre for Parasitology, Entomology and Malaria ControlNational Center for National Centre for Parasitology, Entomology and Malaria ControlMalaria Branch, Centers for Disease Control and PreventionU.S. President’s Malaria Initiative, Malaria Branch, Division Parasitic Diseases and Malaria, Centers for Disease Control and PreventionU.S. President’s Malaria Initiative, Malaria Branch, Division Parasitic Diseases and Malaria, Centers for Disease Control and PreventionMalaria ConsortiumMahidol Oxford Tropical Medicine Research unit (MORU)Institut Pasteur du CambodgeMahidol Oxford Tropical Medicine Research unit (MORU)Abstract Background The WHO recommends single low-dose primaquine (SLDPQ, 0.25 mg/kg body weight) in falciparum-infected patients to block malaria transmission and contribute to eliminating multidrug resistant Plasmodium falciparum from the Greater Mekong Sub region (GMS). However, the anxiety regarding PQ-induced acute haemolytic anaemia in glucose-6-phosphate dehydrogenase deficiency (G6PDd) has hindered its use. Therefore, we assessed the tolerability of SLDPQ in Cambodia to inform national policy. Methods This open randomised trial of dihydroartemisinin-piperaquine (DHAPP) + SLDPQ vs. DHAPP alone recruited Cambodians aged ≥1 year with acute uncomplicated P. falciparum. Randomisation was 4:1 DHAPP+SLDPQ: DHAPP for G6PDd patients and 1:1 for G6PDn patients, according to the results of the qualitative fluorescent spot test. Definitive G6PD status was determined by genotyping. Day (D) 7 haemoglobin (Hb) concentration was the primary outcome measure. Results One hundred nine patients (88 males, 21 females), aged 4–76 years (median 23) were enrolled; 12 were G6PDd Viangchan (9 hemizygous males, 3 heterozygous females). Mean nadir Hb occurred on D7 [11.6 (range 6.4 ─ 15.6) g/dL] and was significantly lower (p = 0.040) in G6PDd (n = 9) vs. G6PDn (n = 46) DHAPP+SLDPQ recipients: 10.9 vs. 12.05 g/dL, Δ = -1.15 (95% CI: -2.24 ─ -0.05) g/dL. Three G6PDn patients had D7 Hb concentrations < 8 g/dL; D7-D0 Hbs were 6.4 ─ 6.9, 7.4 ─ 7.4, and 7.5 ─ 8.2 g/dL. For all patients, mean (range) D7-D0 Hb decline was -1.45 (-4.8 ─ 2.4) g/dL, associated significantly with higher D0 Hb, higher D0 parasitaemia, and receiving DHAPP; G6PDd was not a factor. No patient required a blood transfusion. Conclusions DHAPP+SLDPQ was associated with modest Hb declines in G6PD Viangchan, a moderately severe variant. Our data augment growing evidence that SLDPQ in SE Asia is well tolerated and appears safe in G6PDd patients. Cambodia is now deploying SLDPQ and this should encourage other GMS countries to follow suit. Trial registration The clinicaltrials.gov reference number is NCT02434952.http://link.springer.com/article/10.1186/s12879-019-3862-1MalariaTransmission blockingPrimaquineG6PD deficiencyCambodia |
| spellingShingle | Lek Dysoley Saorin Kim Sergio Lopes Nimol Khim Steven Bjorges Samphornarann Top Chea Huch Huy Rekol Nelli Westercamp Mark M. Fukuda Jimee Hwang Arantxa Roca-Feltrer Mavuto Mukaka Didier Menard Walter R. Taylor The tolerability of single low dose primaquine in glucose-6-phosphate deficient and normal falciparum-infected Cambodians BMC Infectious Diseases Malaria Transmission blocking Primaquine G6PD deficiency Cambodia |
| title | The tolerability of single low dose primaquine in glucose-6-phosphate deficient and normal falciparum-infected Cambodians |
| title_full | The tolerability of single low dose primaquine in glucose-6-phosphate deficient and normal falciparum-infected Cambodians |
| title_fullStr | The tolerability of single low dose primaquine in glucose-6-phosphate deficient and normal falciparum-infected Cambodians |
| title_full_unstemmed | The tolerability of single low dose primaquine in glucose-6-phosphate deficient and normal falciparum-infected Cambodians |
| title_short | The tolerability of single low dose primaquine in glucose-6-phosphate deficient and normal falciparum-infected Cambodians |
| title_sort | tolerability of single low dose primaquine in glucose 6 phosphate deficient and normal falciparum infected cambodians |
| topic | Malaria Transmission blocking Primaquine G6PD deficiency Cambodia |
| url | http://link.springer.com/article/10.1186/s12879-019-3862-1 |
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