SummaryThe Duffy binding protein of Plasmodium vivax (DBP) is a critical adhesion ligand that participates in merozoite invasion of human Duffy-positive erythrocytes. A small outbreak of P. vivax malaria, in a village located in a non-malarious area of Brazil, offered us an opportunity to investigate the DBP immune responses among individuals who had their first and brief exposure to malaria. Thirty-three individuals participated in the five crosssectional surveys, 15 with confirmed P. vivax infection while residing in the outbreak area (cases) and 18 who had not experienced malaria (non-cases). In the present study, we found that only 20% (three of 15) of the individuals who experienced their first P. vivax infection developed an antibody response to DBP; a secondary boosting can be achieved with a recurrent P. vivax infection. DNA sequences from primary/recurrent P. vivax samples identified a single dbp allele among the samples from the outbreak area. To investigate inhibitory antibodies to the ligand domain of the DBP (cysteine-rich region II, DBPII), we performed in vitro assays with mammalian cells expressing DBPII sequences which were homologous or not to those from the outbreak isolate. In non-immune individuals, the results of a 12-month follow-up period provided evidence that naturally acquired inhibitory antibodies to DBPII are short-lived and biased towards a specific allele.

Plasmodium vivax Duffy binding protein (DBP) is functionally important in the erythrocyte invasion process and provides a logical target for vaccine-mediated immunity. In the current study, we demonstrated that DBP is naturally immunogenic in different populations of the Brazilian Amazon, and the proportions of DBP IgG positive subjects increased with exposure to malaria, reaching a peak in those subjects with long-term exposure (> 15 years) in the Amazon area. This profile of antibody response was significantly different from the one observed for the P. vivax merozoite surface protein 1 (MSP1(19)), which was relatively uniform in areas with markedly different levels of malaria transmission. In a small sample of adults with symptomless P. vivax infection, we could not detect any significant correlation between antibodies against these P. vivax proteins and asymptomatic infection. Our study provided an additional insight by demonstrating cumulative exposure as a determinant that acts independently of host age in generation of anti-DBP IgG response.

The function of the Plasmodium vivax Duffy binding protein (DBP) during the erythrocyte invasion process is critical for successful parasite growth and pathogenesis in human infections. Although DBP is the subject of intensive malaria vaccine research, investigations on the functional proprieties of anti‐DBP antibodies in the human population have been limited [Infect Immun68 (2000) 3164]. In the present study, we examined the ability of sera from different populations of the Brazilian Amazon – an area of markedly unstable malaria transmission – to inhibit the erythrocyte‐binding function of the DBP ligand domain (region II, DBPII). We found that long‐term exposure to malaria in the Amazon area elicits DBP‐specific antibodies that inhibit the binding of different DBPII variants to erythrocytes. Despite the great variability of inhibitory antibody responses observed among study participants, we observed a positive correlation between erythrocyte binding‐inhibitory activity and enzyme‐linked immunosorbent assay anti‐DBP antibodies. Of importance, there was a non‐significant tendency towards increased levels of anti‐DBP antibodies among individuals with asymptomatic P. vivax infections.

The diterpene ent-kaur-16-en-19-oic acid (1) was identified as the trypanocidal component of the ethanolic extract from Mikania obtusata D. C. (Asteraceae). This compound presents an IC50 of 0.5 mg/ml (1.66 mM) against the trypomastigote blood form of the Trypanosoma cruzi, the causative agent of Chagas' disease (American trypanosomiasis).

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