BackgroundPlasmodium vivax malaria is a major public health challenge in Latin America, Asia and Oceania, with 130-435 million clinical cases per year worldwide. Invasion of host blood cells by P. vivax mainly depends on a type I membrane protein called Duffy binding protein (PvDBP). The erythrocyte-binding motif of PvDBP is a 170 amino-acid stretch located in its cysteine-rich region II (PvDBPII), which is the most variable segment of the protein.MethodsTo test whether diversifying natural selection has shaped the nucleotide diversity of PvDBPII in Brazilian populations, this region was sequenced in 122 isolates from six different geographic areas. A Bayesian method was applied to test for the action of natural selection under a population genetic model that incorporates recombination. The analysis was integrated with a structural model of PvDBPII, and T- and B-cell epitopes were localized on the 3-D structure.ResultsThe results suggest that: (i) recombination plays an important role in determining the haplotype structure of PvDBPII, and (ii) PvDBPII appears to contain neutrally evolving codons as well as codons evolving under natural selection. Diversifying selection preferentially acts on sites identified as epitopes, particularly on amino acid residues 417, 419, and 424, which show strong linkage disequilibrium.ConclusionsThis study shows that some polymorphisms of PvDBPII are present near the erythrocyte-binding domain and might serve to elude antibodies that inhibit cell invasion. Therefore, these polymorphisms should be taken into account when designing vaccines aimed at eliciting antibodies to inhibit erythrocyte invasion.

Vulnerability, understood as the propensity to be adversely affected, has attained importance in the context of climate change by helping to understand what makes populations and territories predisposed to its impacts. Conditions of vulnerability may vary depending on the characteristics of each territory studied—social, environmental, infrastructural, public policies, among others. Thus, the present study aimed to evaluate what makes the municipalities of the state of Amazonas, Brazil, vulnerable to climate change in the context of the largest tropical forest in the world, and which regions of the State are the most susceptible. A Municipal Vulnerability Index was developed, which was used to associate current socio-environmental characteristics of municipalities with climate change scenarios in order to identify those that may be most affected by climate change. The results showed that poor adaptive capacity and poverty had the most influence on current vulnerability of the municipalities of Amazonas with the most vulnerable areas being the southern, northern, and eastern regions of the state. When current vulnerability was related to future climate change projections, the most vulnerable areas were the northern, northeastern, extreme southern, and southwestern regions. From a socio-environmental and climatic point of view, these regions should be a priority for public policy efforts to reduce their vulnerability and prepare them to cope with the adverse aspects of climate change.

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.

Despite the effectiveness of anterior thalamic nucleus (AN) deep brain stimulation (DBS) for the treatment of epilepsy, mechanisms responsible for the antiepileptic effects of this therapy remain elusive. As adenosine modulates neuronal excitability and seizure activity in animal models, we hypothesized that this nucleoside could be one of the substrates involved in the effects of AN DBS. We applied 5 days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform activity in hippocampal slices. We found that slices from animals given DBS had reduced hippocampal excitability and were less susceptible to develop ictal activity. In live animals, AN DBS significantly increased adenosine levels in the hippocampus as measured by microdialysis. The reduced excitability of DBS in vitro was completely abolished in animals pre-treated with A1 receptor antagonists and was strongly potentiated by A1 receptor agonists. We conclude that some of the antiepileptic effects of DBS may be mediated by adenosine.

The polymerase chain reaction (PCR)-based methods for the diagnosis of malaria infection are expected to accurately identify submicroscopic parasite carriers. Although a significant number of PCR protocols have been described, few studies have addressed the performance of PCR amplification in cases of field samples with submicroscopic malaria infection. Here, the reproducibility of two well-established PCR protocols (nested-PCR and real-time PCR for the Plasmodium 18 small subunit rRNA gene) were evaluated in a panel of 34 blood field samples from individuals that are potential reservoirs of malaria infection, but were negative for malaria by optical microscopy. Regardless of the PCR protocol, a large variation between the PCR replicates was observed, leading to alternating positive and negative results in 38% (13 out of 34) of the samples. These findings were quite different from those obtained from the microscopy-positive patients or the unexposed individuals; the diagnosis of these individuals could be confirmed based on the high reproducibility and specificity of the PCR-based protocols. The limitation of PCR amplification was restricted to the field samples with very low levels of parasitaemia because titrations of the DNA templates were able to detect < 3 parasites/µL in the blood. In conclusion, conventional PCR protocols require careful interpretation in cases of submicroscopic malaria infection, as inconsistent and false-negative results can occur.