Bimodal distribution of Trypanosoma cruzi antibody levels in blood donors from a highly endemic area of Argentina: what is the significance of low-reactive samples?

BACKGROUND: Low-level seroreactive donor samples that are inconsistently detected by different Trypanosoma cruzi immunoassays are common, but the population distribution has not been reported in an endemic region. The objective was to understand the distribution of low-level reactive samples using highly sensitive immunoassays and the relationship with epidemiologic evidence of exposure to T. cruzi. STUDY DESIGN AND METHODS: Blood donors (BDs) were recruited in two blood banks located in Chaco province, in northeastern Argentina, from June 2006 to March 2007. Donors completed a Chagas exposure questionnaire and provided blood samples. All samples were tested in parallel with five contemporary and commercially available enzyme immunoassays for T. cruzi and a subgroup by a chemiluminescent assay. RESULTS: Of the 1423 enrolled donors, 304 (21.4%) tested positive on all assays while 93 (6.5%) were reactive on at least one assay (inconclusive). Epidemiologic evidence of exposure to T. cruzi was significantly higher among positive and inconclusive donors compared to seronegative BD (p values range from 0.01 to <0.001 depending on the exposure). Histograms of the signal-to-cutoff values from all positive samples showed clear bimodal distributions for the whole parasite lysate assays, but not for the one recombinant antigen-based assay. Low antibody level responses were present in 30% to 40% of the reactives, depending on the assay. CONCLUSION: The population of individuals exposed to T. cruzi in highly endemic regions has a bimodal distribution of antibody response to the parasite. Although the clinical significance of low-level reactivity is not fully established, these results may reflect evolving seroreversions after spontaneously resolved infections.

Evidence for Selection of more Adapted Human Immunodeficiency Virus Type 1 Recombinant Strains in a Dually Infected Transfusion Recipient.

Human immunodeficiency virus type-1 (HIV-1) genetic diversity is one of the remarkable characteristics of these viruses, and the mechanisms involved in the selective forces driving HIV-1 evolution are of great interest. Samples from hosts infected with multiple distinct strains represent a valuable in vivo resource to investigate the role of recombination in the natural evolution of HIV-1. This work describes a detailed study regarding the evolution of the envelope gene (env) (C2-V5 region) in a dually infected child who received blood transfusions simultaneously from two distinct HIV-1 infected donors. In this study, we were able to directly compare the data obtained from the dually infected recipient with data obtained from two other singly HIV-1 infected children who had received blood transfusion from each of the two donors. Sequences from the singly infected children clustered into two distinct groups, each related to the respective donor-derived sequence by phylogenetic analysis, and hence were consistent with the epidemiological data. In the case of the dually infected child, a high degree of recombination between the two donor-derived sequences was observed at the C2-V3 region, whereas in the V4-V5 region selection of only one derived donor sequence was seen. Measurement of nonsynonymous versus synonymous substitution rates at each region revealed that negative selection was the main evolutionary force acting on the viral population of the dually infected child, regardless of the genetic mechanism by which each region evolved. Based on direct comparison with data obtained for the two singly infected children we propose that the higher amount of viral diversity observed in HIV-1 multi-infection events, as in the case of the dually infected patient, might contribute to maximizing selective advantage and possibly minimizing immune response. We conclude that recombination shaped by selective forces may increase the adaptive potential of HIV-1.