Duffy blood system and G6PD genetic variants in vivax malaria patients from Manaus, Amazonas, Brazil.

BACKGROUND: Over a third of the world's population is at risk of Plasmodium vivax-induced malaria. The unique aspect of the parasite's biology and interactions with the human host make it harder to control and eliminate the disease. Glucose-6-phosphate dehydrogenase (G6PD) deficiency and Duffy-negative blood groups are two red blood cell (RBC) variations that can confer protection against malaria. METHODS: Molecular genotyping of G6PD and Duffy variants was performed in 225 unrelated patients (97 with uncomplicated and 128 with severe vivax malaria) recruited at a Reference Centre for Infectious Diseases in Manaus. G6PD and Duffy variants characterizations were performed using Real Time PCR (qPCR) and PCR-RFLP, respectively. RESULTS: The Duffy blood group system showed a phenotypic distribution Fy(a + b-) of 70 (31.1%), Fy(a + b +) 96 (42.7%), Fy(a-b +) 56 (24.9%) and Fy(a-b-) 1 (0.44%.) The genotype FY*A/FY*B was predominant in both uncomplicated (45.3%) and severe malaria (39.2%). Only one Duffy phenotype Fy(a-b) was found and this involved uncomplicated vivax malaria. The G6PD c.202G > A variant was found in 11 (4.88%) females and 18 (8.0%) males, while c.376A > G was found in 20 females (8.88%) and 23 (10.22%) male patients. When combined GATA mutated and c.202G > A and c.376A > G mutated, was observed at a lower frequency in uncomplicated (3.7%) in comparison to severe malaria (37.9%). The phenotype Fy(a-b +) (p = 0.022) with FY*B/FY*B (p = 0.015) genotype correlated with higher parasitaemia. CONCLUSIONS: A high prevalence of G6PD c202G > A and c.376A > G and Duffy variants is observed in Manaus, an endemic area for vivax malaria. In addition, this study reports for the first time the Duffy null phenotype Fy(a-b-) in the population of the Amazonas state. Moreover, it is understood that the relationship between G6PD and Duffy variants can modify clinical symptoms in malaria caused by P. vivax and this deserves to be further investigated and explored among this population.

Outcome of B-Cell Acute Lymphoblastic Leukemia in Brazilian Children: Immunophenotypical, Hematological, and Clinical Evaluation.

The aim of this study is to investigate the clinical, hematological, and immunophenotypic characteristics of Brazilian children with B-cell acute lymphoblastic leukemia (B-ALL) to identify prognostic biomarkers of the disease. Thirty-three children newly diagnosed with B-ALL were followed between March 2004 and December 2009. Information about the demographic profile, diagnosis, immunophenotype, clinical manifestations, and disease outcome were gathered from the patients' medical records. Of the 33 patients with B-ALL, 18 were male and 15 female. Eighteen patients were classified as high risk; 13 as low risk, and 2 as true low risk. The frequencies of cluster of differentiation (CD)10, CD19, and CD20 antigens were 69.7%, 81.8%, and 18.2%, respectively. Six patients (18.2%) had aberrant expression of myeloid antigens. At diagnosis, patients immunopositive for CD20 had elevated white blood cell counts (P = 0.018) and lower platelet counts (P = 0.017). The 6-year overall survival was 67.5%± 3.47%. Our results demonstrate the distinct immunophenotypic and prognostic characteristics of patients with B-ALL, which can be related to the Brazilian racial admixture. Consequently, these results will most likely aid in the selection of additional prognostic markers and their use in monitoring the clinical manifestations and treatment response among B-ALL patients.

Prevalence and molecular characterization of ß-thalassemia in the state of Bahia, Brazil: first identification of mutation HBB: c.135delC in Brazil.

ß-Thalassemia (ß-thal) is a hereditary disease with at least 200 known causative molecular defects, with a limited number of distinct mutations predominating in any given population. The Brazilian population is one of the most heterogeneous in the world. Although occurrences of ß-thal in this country have been recognized for a long time and previous studies have shown important regional differences related to the mutational profile, no extensive analysis of mutations of the HBB gene has been carried out in Brazil. We examined 1011 teenagers from Bahia, a state located in the northeast of Brazil. Hematological data were obtained using automated cell counting, hemoglobin (Hb) profiles were studied by high performance liquid chromatography (HPLC), and DNA was analyzed by automated sequencing. None of the four Mediterranean mutations that are most frequently found in South and Southeast Brazil (HBB: c.118C>T; HBB: c.93-21G>A; HBB: c.92+1G>A; HBB: c.92+6T>C), was found to be responsible for thalassemia in the cases that we studied. One heterozygote for a frameshift mutation at codon 44 (-C) was identified. This is the first study to determine the prevalence and profile of ß-thal in Bahia State. For the first time in Brazil, we report the occurrence of the HBB: c.135delC mutation in the ß-globin gene.

Severe clinical presentation of visceral leishmaniasis in naturally infected dogs with disruption of the splenic white pulp.

In this work, we investigated the association between the disruption of splenic lymphoid tissue and the severity of visceral leishmaniasis in dogs. Clinical and laboratory data from 206 dogs were reviewed. Spleen sections collected during the euthanasia of these animals were analyzed, and the splenic lymphoid tissue samples were classified as well organized (spleen type 1), slightly disorganized (spleen type 2), or moderately to extensively disorganized (spleen type 3). Of 199 dogs with evidence of Leishmania infection, 54 (27%) had spleen type 1, 99 (50%) had spleen type 2, and 46 (23%) had spleen type 3. The number of clinical signs associated with visceral leishmaniasis was significantly higher in the animals with evidence of Leishmania infection and spleen type 2 or 3 than in the animals with spleen type 1. Alopecia, anemia, dehydration, dermatitis, lymphadenopathy, and onychogryphosis were all more frequent among animals with evidence of Leishmania infection and spleen type 3 than among the dogs with evidence of Leishmania infection and spleen type 1. The association between the severity of canine visceral leishmaniasis and the disorganization of the splenic lymphoid tissue was even more evident in the group of animals with positive spleen culture. Conjunctivitis and ulceration were also more common in the animals with spleen type 3 than in the animals with spleen type 1. The serum levels (median, interquartile range) of albumin (1.8, 1.4-2.3 g/dL) and creatinine (0.7, 0.4-0.8 mg/dL) were significantly lower and the serum levels of aspartate aminotransferase were significantly higher (57, 39-95 U) in animals with spleen type 3 than in animals with spleen type 1 (2.8, 2.4-3.4 g/dL; 0.9, 0.7-1.2 mg/dL and 23, 20-32 U, respectively). Our data confirm the hypothesis that disruption of the splenic lymphoid tissue is associated with a more severe clinical presentation of canine visceral leishmaniasis.

The mitochondrial genome of the phytopathogenic basidiomycete Moniliophthora perniciosa is 109 kb in size and contains a stable integrated plasmid.

We present here the sequence of the mitochondrial genome of the basidiomycete phytopathogenic hemibiotrophic fungus Moniliophthora perniciosa, causal agent of the Witches' Broom Disease in Theobroma cacao. The DNA is a circular molecule of 109,103 base pairs, with 31.9% GC, and is the largest sequenced so far. This size is due essentially to the presence of numerous non-conserved hypothetical ORFs. It contains the 14 genes coding for proteins involved in the oxidative phosphorylation, the two rRNA genes, one ORF coding for a ribosomal protein (rps3), and a set of 26 tRNA genes that recognize codons for all amino acids. Seven homing endonucleases are located inside introns. Except atp8, all conserved known genes are in the same orientation. Phylogenetic analysis based on the cox genes agrees with the commonly accepted fungal taxonomy. An uncommon feature of this mitochondrial genome is the presence of a region that contains a set of four, relatively small, nested, inverted repeats enclosing two genes coding for polymerases with an invertron-type structure and three conserved hypothetical genes interpreted as the stable integration of a mitochondrial linear plasmid. The integration of this plasmid seems to be a recent evolutionary event that could have implications in fungal biology. This sequence is available under GenBank accession number AY376688.