Distinction of recrudescences from new infections by pcr‐rflp analysis in a comparative trial of cgp 56 697 and chloroquine in Tanzanian children.

Abstract

SummaryOBJECTIVE To test the efficacy of a new compound drug (CGP 56 697) against acute, uncomplicated falciparum malaria. METHOD Reappearing parasites were analysed by PCR-RFLP within a randomized controlled trial. 130 patients received chloroquine and 130 patients were treated with CGP 56 697. Samples from 96 patients with parasitological failure were tested by PCR-RFLP for MSP2 of Plasmodium falciparum. Seven days after treatment 32 patients of the chloroquine control group with reappearing parasites were tested by PCR and one infection was unequivocally determined as a new infection. After 7 days, in the CGP 56 697 group, 6 samples were tested in which one new infection was identified. Similar observations were made one and three weeks later in both groups. RESULTS Although a high multiplicity of infections on admission was observed, there was no significant correlation between multiplicity and either recrudescence or new infection. Patients in both treatment groups with subsequent recrudescent parasites had higher initial mean parasite densities than patients who cleared. Those of the patients with recrudescent parasites who were treated with CGP 56 697 had higher initial parasite densities than those treated with chloroquine. The rate of re-infection increased with time as expected in holoendemic areas and appeared to be higher in chloroquine patients. Generally, CGP 56 697 showed a superior clearance rate, successfully cleared higher parasite densities and suppressed new infections over a longer period of time. CONCLUSION The PCR analysis confirmed that reinfections beyond day 7 are significant in areas highly endemic for malaria and showed the necessity of excluding these when estimating 14 day clearance rates. Provided new infections are excluded, the 28-day clearance rate can also be used to determine the efficacy of antimalarial drugs in highly endemic areas, and adds to our knowledge of drug resistance and dynamics of infections in people living in such areas. keywords malaria, Plasmodium falciparum, drug treatment, resistance, polymerase chain reaction, artemether, benflumetol correspondence Hans-Peter Beck, Swiss Tropical Institute,

2. Genotypes of merozoite surface protein 2 of Plasmodium falciparum in Tanzania

“…Such applications include comparisons of baseline and recrudescent genotypes in vaccine or drug trials in order to distinguish treatment failure from reinfection (IRION et al, 1998;SNOUNOU & BECK, 1998), and studies of infection dynamics (SMITH et al, 1999b). High resolution typing of a single locus gives rise directly to patterns of appearance and disappearance of individual infections.…”

Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with chloroquine to treat acute falciparum malaria in Tanzanian children aged 1–5 years

“…less than 5%, had early recrudescence. Four of the 8 children tested by PCR had confirmed new infections (Irion et al 1998). For the chloroquine group the 62 failures from the first week had increased by a further 25 by Day 14.…”

“…However, it seemed to positively affect the 28 days cure rate by as much as 23% in the CGP 56697 group (14/30 children without vs. 29 of 42 with detectable chloroquine). The full evaluation of the parasite genotype dynamics using PCR technology is presented elsewhere (Irion et al 1998). …”

Immunoglobulin G Subclass-Specific Responses against Plasmodium falciparum Merozoite Antigens Are Associated with Control of Parasitemia and Protection from Symptomatic Illness

“…P. falciparum was detected in 67.5% of subjects at enrollment by LDR-FMA and in 40.3% by light microscopy. Samples collected at baseline and from the first symptomatic infection were genotyped to identify MSP2 alleles (FC27 or 3D7), according to methods published previously (16,22).…”