Intermittent presumptive treatment for malaria

Abstract

A better understanding of the pharmacodynamics of intermittent presumptive treatment, says White, will guide more rational policymaking

Figure 1. In Vivo Antimalarial Pharmacodynamics

The parasite burden in an adult (vertical axis) is shown in green. After parasite burden expands to the point where it causes illness, treatment is given (red arrow), which causes a log-linear decline in parasite numbers until concentrations of the antimalarial drug (grey shading) fall below the MPC. As the antimalarial blood levels fall further, the decline in parasite burden slows until it reaches a multiplication rate of one (the antimalarial concentration at this point is the in vivo MIC). The parasite population then expands to cause a recrudescence six weeks later. The sigmoid concentration–effect relationship is shown in brown; it is depicted in the reverse direction to that normally drawn. PMR, parasite multiplication rate.

Figure 2. Blood Concentration Profiles of Two Antimalarials with Different Elimination Profiles

The examples shown here are mefloquine (orange) and chloroquine (pink). An increase in MIC has different effects on the shortening of post-treatment suppressive prophylaxis (hatched bars). MIC_R, MIC for resistant parasites; MIC_S, MIC for sensitive parasites.

Figure 3. Hypothetical Parasite Burden Profiles during Pregnancy with SP IPT in a High-Transmission Setting

Entomological inoculation rate is about 50 infectious bites per person per year. Note that many infections self-cure (each infection is depicted as a green line). The hatched bars represent the duration of “suppressive prophylactic activity”, and the solid bars represent the period during which parasite multiplication is suppressed (i.e., levels exceed the in vivo MIC). The horizontal dotted line at 10⁸ parasites represents the level at which malaria can be detected on a blood film. (A) represents a drug-sensitive area; (B) represents a moderately resistant area.

Figure 4. Relationship between MIC and PTP

The proportional increase in malaria parasite MIC with resistance is plotted against the shortening of the duration of PTP, expressed as multiples of the terminal half-life. This applies only to drugs for which suppressive antimalarial prophylaxis occurs in the terminal elimination phase (i.e., most drugs).