2012-09-10-世界卫生组织-Meeting_report_of_the_Evidence_Review_Group_on_the_safety_and_effectiveness_of_single_dose_primaquine_as_a_P._falciparum_gametocytocide_19页_404kb

Malaria Policy Advisory Committee Meeting Summary (Session 5: 11-13 September 2012, WHO HQ)
Primaquine as Gametocytocide for P. falciparum Malaria

Background
primaquine, introduced in the early 1950s, is the most widely used 8-aminoquinoline antimalarial drug, particularly for radical treatment of P. vivax and P. ovale malaria and as a single-dose gametocytocide for P. falciparum. Its main limitation is haemolytic toxicity in individuals deficient in glucose-6-phosphate dehydrogenase (G6PDd), an inherited condition prevalent in malaria-endemic regions. The World Health Organisation (WHO) currently recommends adding 0.75 mg/kg single-dose primaquine to Artemisinin Combination Therapy (ACT) in low-transmission areas, especially where artemisinin resistance threatens. However, limited G6PD testing and uncertainty about deficiency prevalence hinder implementation.

Key Findings & Recommendations:

1. Transmission Reduction: Low-dose (0.25 mg/kg base) primaquine added to ACT significantly reduces P. falciparum transmission, especially in areas with artemisinin resistance.
2. Safety:
   • Harm occurs primarily in G6PD-deficient individuals; haemolytic anaemia risk depends on dose and enzyme deficiency variant.
   • A single 0.25 mg/kg dose (adult equivalent 15 mg) appears safer than the WHO-recommended 0.75 mg/kg dose in low-G6PD-risk areas.
   • Severe adverse events are rare, but overdose or suboptimal dosing increases risk mainly in children.
3. Detection & Mitigation:
   • Point-of-care (POC) G6PD testing is limited due to cost and infrastructure; alternatives being developed.
   • Patients should monitor urine colour for haemolysis signs and seek medical help if adverse effects (dark urine, jaundice) occur.
   • Ethical debate exists on mandatory use for public health benefits, with recommendations for phased implementation using lower doses.

Outcomes:
The WHO Evidence Review Group revised recommendations to prioritise 0.25 mg/kg primaquine for adults in suitable settings, subject to G6PD testing availability. High priority is given to research for improved POC testing, alternative transmission-blocking drugs, and resolving safety questions in vulnerable populations like children, pregnant women, and infants.