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Single low-dose primaquine for blocking transmission of plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa
- Source :
- BMC medicine, BMC Medicine, BMC Medicine, BioMed Central, 2018, 16 (1), pp.11. ⟨10.1186/s12916-017-0990-6⟩, BMC medicine, Vol. 16, No 1 (2018) P. 11, BMC Medicine, Vol 16, Iss 1, Pp 1-14 (2018), BMC Medicine, 2018, 16 (1), pp.11. ⟨10.1186/s12916-017-0990-6⟩
- Publication Year :
- 2018
-
Abstract
- Background In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. Methods Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15–0.4 mg PQ base/kg for children aged 1–5 years and 0.15–0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6–11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box–Cox transformation power exponential and tested PQ doses of 1–15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. Results From the Box–Cox transformation power exponential model, five age categories were selected: (i) 6–11 months (n = 39,886, 6.03%), (ii) 1–5 years (n = 261,036, 45.46%), (iii) 6–9 years (n = 20,770, 3.14%), (iv) 10–14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12–0.25), (ii) 0.21 (0.13–0.37), (iii) 0.25 (0.16–0.38), (iv) 0.26 (0.15–0.38) and (v) 0.27 (0.17–0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. Conclusions We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 − 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination. Electronic supplementary material The online version of this article (doi:10.1186/s12916-017-0990-6) contains supplementary material, which is available to authorized users.
- Subjects :
- Male
Primaquine
Antimalarials / therapeutic use
lcsh:Medicine
MESH: Dose-Response Relationship, Drug
MESH: Clinical Protocols
MESH: Aged, 80 and over
0302 clinical medicine
Clinical Protocols
MESH: Child
Epidemiology
030212 general & internal medicine
Malaria, Falciparum
Child
MESH: Plasmodium falciparum
Aged, 80 and over
MESH: Aged
MESH: Middle Aged
biology
MESH: Malaria, Falciparum
Age Factors
11 Medical And Health Sciences
General Medicine
Middle Aged
MESH: Primaquine
MESH: Infant
3. Good health
MESH: Glucosephosphate Dehydrogenase Deficiency
Tolerability
MESH: Young Adult
Child, Preschool
Primaquine / administration & dosage
Female
[SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Research Article
medicine.drug
Adult
medicine.medical_specialty
Adolescent
Plasmodium falciparum
030231 tropical medicine
Antimalarials / adverse effects
Antimalarials
Malaria, Falciparum / prevention & control
Young Adult
03 medical and health sciences
Pharmacokinetics
Age-based dosing
General & Internal Medicine
Internal medicine
parasitic diseases
medicine
Humans
[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
MESH: Africa South of the Sahara
Dosing
Africa South of the Sahara
ddc:613
Aged
MESH: Adolescent
MESH: Age Factors
MESH: Humans
Dose-Response Relationship, Drug
business.industry
lcsh:R
Malaria, Falciparum / transmission
MESH: Child, Preschool
Infant
MESH: Adult
medicine.disease
biology.organism_classification
MESH: Antimalarials
MESH: Male
Malaria
Regimen
Glucosephosphate Dehydrogenase Deficiency
Primaquine / adverse effects
Primaquine / therapeutic use
Antimalarials / administration & dosage
Malaria, Falciparum / drug therapy
Transmission blocking
Human medicine
business
MESH: Female
Subjects
Details
- Language :
- English
- ISSN :
- 17417015
- Database :
- OpenAIRE
- Journal :
- BMC medicine
- Accession number :
- edsair.doi.dedup.....fe2983e09d290a16198c23cc519fcde1