Mechanisms involved in severe P. vivax malaria remain unclear. Parasite polymorphisms, parasite load and host cytokine profile may influence the course of infection. In this study, we investigated the influence of circumsporozoite protein (CSP) polymorphisms on parasite load and cytokine profile in patients with vivax malaria. A cross-sectional study was carried out in three cities: São Luís, Cedral and Buriticupu, Maranhão state, Brazil, areas of high prevalence of P. vivax. Interleukin (IL)-2, IL-4, IL-10, IL-6, IL-17, tumor necrosis factor alpha (TNF-α, interferon gamma (IFN-γ and transforming growth factor beta (TGF-β were quantified in blood plasma of patients and in supernatants from peripheral blood mononuclear cell (PBMC) cultures. Furthermore, the levels of cytokines and parasite load were correlated with VK210, VK247 and P. vivax-like CSP variants. Patients infected with P. vivax showed increased IL-10 and IL-6 levels, which correlated with the parasite load, however, in multiple comparisons, only IL-10 kept this association. A regulatory cytokine profile prevailed in plasma, while an inflammatory profile prevailed in PBMC culture supernatants and these patterns were related to CSP polymorphisms. VK247 infected patients showed higher parasitaemia and IL-6 concentrations, which were not associated to IL-10 anti-inflammatory effect. By contrast, in VK210 patients, these two cytokines showed a strong positive correlation and the parasite load was lower. Patients with the VK210 variant showed a regulatory cytokine profile in plasma, while those infected with the VK247 variant have a predominantly inflammatory cytokine profile and higher parasite loads, which altogether may result in more complications in infection. In conclusion, we propose that CSP polymorphisms is associated to the increase of non-regulated inflammatory immune responses, which in turn may be associated with the outcome of infection.

In an effort to identify novel therapeutic alternatives for the treatment of malaria, the present study evaluated the antimalarial effect of the crude hydroalcoholic extract (HCE) from the leaves of Chenopodium ambrosioides L. For this purpose, the molecular affinity between the total proteins from erythrocytes infected with Plasmodium falciparum and HCE or chloroquine was evaluated by surface plasmon resonance (SPR). Subsequently, the plasmodicidal potential of HCE was assessed in a P. falciparum culture. Using BALB/c mice infected with Plasmodium berghei intraperitoneally (ip.), we evaluated the effects of ip. treatment, for three consecutive days (day 7, 8, and 9 after infection), with chloroquine (45 mg/kg) or HCE (5 mg/kg), considering the survival index and the parasitaemia. The groups were compared to an untreated control group that receives only PBS at the same periods. The results indicated that HCE could bind to the total proteins of infected erythrocytes and could inhibit the parasite growth in vitro (IC = 25.4 g/mL). The in vivo therapeutic treatment with HCE increased the survival and decreased the parasitaemia in the infected animals. Therefore, the HCE treatment exhibited a significant antiplasmodial effect and may be considered as a potential candidate for the development of new antimalarial drugs.

Chronic use of statins may have anti-inflammatory action, promoting immunomodulation and survival in patients with sepsis. This study aimed to analyze the effects of pretreatment with simvastatin in lethal sepsis induced by cecal ligation and puncture (CLP). Male Swiss mice received prophylactic treatment with simvastatin or pyrogen-free water orally in a single daily dose for 30 days. After this period, the CLP was performed. Naïve and Sham groups were performed as non-infected controls. Animal survival was monitored for 60 h after the CLP. Half of mice were euthanized after 12 h to analyze colony-forming units (CFUs); hematological parameters; production of IL-10, IL-12, IL-6, TNF-α, IFN-γ, and MCP-1; cell counts on peritoneum, bronchoalveolar lavage (BAL), bone marrow, spleen, and mesenteric lymph node; immunephenotyping of T cells and antigen presenting cells and production of hydrogen peroxide (H2O2). Simvastatin induced an increase in survival and a decrease in the CFU count on peritoneum and on BAL cells number, especially lymphocytes. There was an increase in the platelets and lymphocytes number in the Simvastatin group when compared to the CLP group. Simvastatin induced a greater activation and proliferation of CD4+ T cells, as well as an increase in IL-6 and MCP-1 production, in chemotaxis to the peritoneum and in H2O2 secretion at this site. These data suggest that simvastatin has an impact on the survival of animals, as well as immunomodulatory effects in sepsis induced by CLP in mice.

Background: Recent studies have found an association between Helicobacter pylori infection and prediabetes. Whether H. pylori per se or host factors are involved in the disturbance of glycated hemoglobin needs further investigation. The aim of this study was to determine the association of glycated hemoglobin levels with endoscopic diagnosis and the inflammatory response in H. pylori infection. Methods: A cross-sectional study was carried out in 88 dyspeptic non-diabetic adults who underwent esophagogastroduodenoscopy. The diagnosis of H. pylori infection was performed through urease test and histopathological exam. Cases were initially distributed into two groups: control (without H. pylori infection, n = 22) and HP (patients with H. pylori infection, n = 66). HbA1c was measured to determine prediabetes status according to the American Diabetes Association criteria, and then the groups were subdivided into non-prediabetic (n = 14), prediabetic (n = 8), non-prediabetic HP (n = 26) and prediabetic HP (n = 40) groups. Gastric mucosa was histologically evaluated to determine H. pylori density and inflammatory activity according to Sydney System. To investigate the balance of anti-inflammatory and pro-inflammatory cytokines we measured interleukin 10 (anti-inflammatory) and Tumor Necrosis Factor-a (proinflammatory) in the plasma or in the gastric mucosa. Results: Patients with H. pylori infection had higher mean HbA1c levels than those without H. pylori infection. However, increased HbA1c levels were not associated with H. pylori-related factors but with the bacterial density, the intensity of inflammation and the activity of the chronic gastritis. In addition, H. pylori infection per se did not alter