Influence of HLA-DRB-1 alleles on the production of antibody against CSP, MSP-1, AMA-1, and DBP in Brazilian individuals naturally infected with Plasmodium vivax

We evaluated the influence of allelic frequency of the human leukocyte antigen (HLA) -DRB1 on the acquisition of antibody response against malaria sporozoite and merozoite peptides in patients with Plasmodium vivax malaria acquired in endemic areas of Brazil. IgG antibodies were detected by enzyme-linked immunosorbent assay against four peptides of circumsporozoite protein (CSP) (amino, carboxyl, and VK210 and VK247 repeats) and peptides of merozoite surface protein 1 (MSP-1), apical membrane antigen 1 (AMA-1), and Duffy-binding protein (DBP). We found an association between HLA-DR3 and HLA-DR5 alleles and lack of antibody response to CSP amino terminal, as well as an association between HLA-DR3 and the highest antibody response to MSP1 (Pv200L). In conclusion, we suggest a potential regulatory role of the HLA-DRB1 alleles in the production of antibodies to a conserved region of P. vivax CSP and MSP1 in Brazilian population exposed to malaria.     

Severe Thrombotic Events Associated with Dengue Fever,Brazil

Dengue fever has been a major problem in hospital settings in Brazil for the past 15 years. The main concern has been the severe forms, i.e., dengue hemorrhagic fever and dengue shock syndrome. Hemorrhagic events of different degrees have also been a major concern. We report five cases of large vein thrombotic events associated with the acute phase of dengue fever, including a previously non-reported case of mesenteric vein thrombosis. Complications such as these could have been overlooked in the diagnosis of dengue fever, given that the major concern is the hemorrhagic event.Dengue fever frequently affects Brazil, where thousands of cases have been diagnosed annually and all four dengue virus serotypes (DENV-1 through DENV-4) have been reported, sometimes concurrently in the same region.^1,2 Hemorrhagic events of different degrees have often been described in dengue, but thrombotic events have not been extensively reported, despite the wide range of increased procoagulant activity during illness.^1,3–8 During a recent outbreak, several cases of thrombotic events affected large veins in dengue fever patients. We report cases of unusual and overlooked complication of dengue fever.From January 2011 through March 2011 during a local outbreak of dengue fever caused by DENV-1 and DENV-2 according to local health officials, five patients were given diagnoses by imaging techniques (pulmonary computed tomography angiography, cholangio-magnetic resonance imaging, and Doppler ultrasound of lower extremities) as having large vessel thrombosis. These patients were part of 92 serologically confirmed (by immunochromatographic strip test or IgM antigen-capture enzyme-linked immunosorbent assay) patients with dengue (60% women and 40% men, median age = 39 years, age range = 10–99 years) admitted to Monte Sinai Hospital (200 beds) in Juiz de Fora, (population = 500,000), Minas Gerais, Brazil. This study was approved by the Ethical Committee of Monte Sinai Hospital.Twenty-three patients (25%) were classified as having dengue shock syndrome or dengue hemorrhagic fever and 4 deaths were recorded (case-fatality rate = 4.3%). These thrombotic patients represented 5.4% of all dengue inpatients. All thrombotic events were identified within the first five days of illness, and all patients had symptoms compatible with the reported thrombotic event at hospital admission. No thrombotic events were identified among the remaining patients during hospitalization, and none of the patients them received drugs for thrombosis prophylaxis, which is contraindicated in dengue.The demographic and clinical characteristics of the five patients are summarized in Figure 1), which was associated with jaundice and severe sepsis by Escherichia coli demonstrated by blood culture. Known risk factors for thrombotic events such as smoking, use of oral contraceptives, and being overweight were absent in all patients and none had had any similar diagnosis or symptoms.Open in a separate windowFigure 1.T1-weighted cholangio-magnetic resonance image with contrast of dengue patient 5 showing the superior mesenteric vein (SMV) with a large thrombus (arrow) occupying the vein lumen. SMA = superior mesenteric artery; IVC = inferior vena cava; Ao = aorta.

Table 1

Demographic, clinical, and laboratory characteristics of five dengue fever patients with thrombotic events, Brazil^*