A COMPARISON OF TRANSMISSION-BLOCKING ACTIVITY WITH REACTIVITY IN A PLASMODIUM-FALCIPARUM 48 45-KD MOLECULE-SPECIFIC COMPETITION ENZYME-LINKED-IMMUNOSORBENT-ASSAY/

Monoclonal antibodies (MAbs) 32F1 and 32F3 react with two independent epitopes of a protein doublet with molecular weights of 48 and 45 kilo daltons (kD) expressed on the surface of Plasmodium falciparum (Pfs48/ 45) macrogametes and zygotes; only 32F3 blocks transmission. These MA bs were used to develop a Pfs48/45-specific competition enzyme-linked immunosorbent assay (ELISA) using 32F1 to capture antigen and labeled 32F3 for quantification and analysis of the contribution of antibodies in human serum to transmission-blocking activity. A comparison analys is was used to determine agreement of competition ELISA titers and tra nsmission-blocking activity as observed in the bioassay in three group s of serum samples: 37 from European travelers with previous exposure to malaria, 56 from gametocyte carriers, and 66 from schoolchildren fr om a malaria-endemic area in Cameroon. The index of agreement between outcomes of the ELISA and transmission-blocking assay in gametocyte ca rriers and in travelers was specifically defined as fair-to-moderate; in schoolchildren the agreement was not significant. The combined anal ysis of all sera showed a significant and fair-to-moderate agreement b etween the results of the competition ELISA and the transmission-block ing assay, with a relative specificity of 94% (of 105 cases negative i n the transmission-blocking assay, 99 were also negative in the compet ition ELISA) and a relative sensitivity of 44% (of 54 cases positive i n the transmission-blocking assay, 24 were also positive in the compet ition ELISA). This study shows that a positive C48/45-ELISA is indicat ive for transmission-blocking activity in the mosquito assay, while a negative result does not exclude transmission-blocking activity.