Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria.

BACKGROUND: In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax. METHODS: The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen. RESULTS: The proposed weight-based regimen has 5 dosing bands: (i) 5-7 kg, 5 mg, resulting in 0.71-1.0 mg/kg/day; (ii) 8-16 kg, 7.5 mg, 0.47-0.94 mg/kg/day; (iii) 17-40 kg, 15 mg, 0.38-0.88 mg/kg/day; (iv) 41-80 kg, 30 mg, 0.37-0.73 mg/kg/day; and (v) 81-100 kg, 45 mg, 0.45-0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6-11 months, 5 mg, 0.43-1.0 mg/kg/day; (ii) 1-5 years, 7.5 mg, 0.35-1.25 mg/kg/day; (iii) 6-14 years, 15 mg, 0.30-1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35-1.07 mg/kg/day. CONCLUSION: The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.

Assessment of net lending strategy to better reach mobile and migrant populations in malaria endemic areas of Cambodia.

BACKGROUND: In Cambodia, internal migration involves migrants moving from non-malaria endemic areas to malaria endemic areas and vice versa. The majority of them work in farms or forests with various malaria transmission levels. In Cambodia, as one of the national approaches to ensure LLIN accessibility and use among mobile and migrant populations (MMPs), a lending scheme of long lasting insecticide treated nets (LLINs) was initiated among farm workers. Through this net lending program, LLINs and long-lasting insecticide treated hammock nets (LLIHNs) will be distributed annually at workplace (e.g. longstanding farms, plantations, industrial sites, as identified by operational district and health center staff) on a ratio of one LLIN per one worker. The main objective of this study is to assess MMPs' accessibility to LLINs through a lending scheme with plantation owners in remote malaria endemic areas of Cambodia. METHODS: The study used a cross-sectional survey among MMPs using two-stage cluster sampling method. The sampling frame is the list of farms in the four provinces of Banteay Meanchey, Battambang, Pailin, and Pursat in western and northwestern Cambodia bordering with Thailand where the LLIN lending scheme was implemented and where an estimated 100 000 MMPs worked annually. The assessment was carried out from January to February 2013 in these four provinces. It was estimated that 768 workers would be required. RESULTS: A total of 702 MMPs were interviewed. The ratio of male: female is 1:1. The age group of 21-60 was the largest accounting for 77.6%. About 91% of the MMPs stayed on the farm for less than 6 months. 93.2% of them owned either untreated or insecticide treated nets. LLINs and LLIHNs accounted for 89.5%; and 46.6% of them borrowed the nets from a lending scheme. Among those workers who have LLINs/LLIHNs, 99% slept under LLINs/LLIHNs the night before. However, only 87.4% knew that sleeping under LLINs/LLIHNs protects against malaria. CONCLUSIONS: LLIN lending scheme provides an important delivery channel for a substantial percentage of net accessibility (46.6%) to the Cambodian national free-net distribution campaign in remote malaria endemic areas.