Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance

Malaria Journal

Table 1 The rapid selection of pyrimethamine resistance in-vivo; recrudescence proportions in volunteers with falciparum malaria treated with pyrimethamine; from Martin and Arnold 1968 (21).

Pyrimethamine dose (mg)	Highest observed parasite count/uL
	<1000	1000 to 20,000	20,000 to 100,000	100,000 to 200,000	>200,000
12.5	2/5	1/1
25	0/10	5/5
50			2/2
100		0/1	0/1	0/1	1/1
150				0/1

Volunteers were given the Ugandan strain of P. falciparum by intravenous injection and treated with a single dose of pyrimethamine. All recrudescences occurred within 21 days. Recrudescent infections were highly resistant to treatment with 150 mg of pyrimethamine. The parasites were obtained from a child in Kampala in 1965. Pyrimethamine had been used extensively over the previous ten years, but not apparently in the area where this child originated from. Nevertheless the parasites may already have had some degree of resistance (i.e. resistance mutations in Pfdhfr).

ISSN: 1475-2875