Luzia H. Carvalho

Fundação Oswaldo Cruz

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Cor Jésus Fernandes Fontes

Universidade Federal de Mato Grosso

Cristiana Ferreira Alves de Brito

Fundação Oswaldo Cruz

Taís Nóbrega de Sousa

Karolinska Institutet

Flora Satiko Kano

Fundação Oswaldo Cruz

John H. Adams

Center for Global Health

Irene S. Soares

Universidade de São Paulo

Francis B. Ntumngia

University of South Florida

Antoniana U. Krettli

Fundação Oswaldo Cruz

Bruno Antônio Marinho Sanchez

Universidade Federal de Mato Grosso

Luiz F. F. Guimarães

Fundação Oswaldo Cruz

Cooperative Institutions

Fundação Oswaldo Cruz

144

Universidade Federal de Minas Gerais

Universidade de São Paulo

Universidade Estadual Paulista (Unesp)

Universidade Federal de Mato Grosso

Faculdade de Medicina de São José do Rio Preto

Faculdades Oswaldo Cruz

Fundação de Medicina Tropical

Instituto Evandro Chagas

University of Bonn

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Plasmodium simium, a Plasmodium vivax-Related Malaria Parasite: Genetic Variability of Duffy Binding Protein II and the Duffy Antigen/Receptor for Chemokines

PLoS ONE (2015)

Daniela Camargos Costa Gabriela Maíra Pereira de Assis Flávia Alessandra de Souza Silva Flávia Carolina Faustino de Araújo Júlio César de Souza

Plasmodium simium is a parasite from New World monkeys that is most closely related to the human malaria parasite Plasmodium vivax; it also naturally infects humans. The blood-stage infection of P. vivax depends on Duffy binding protein II (PvDBPII) and its cognate receptor on erythrocytes, the Duffy antigen receptor for chemokines (hDARC), but there is no information on the P. simium erythrocytic invasion pathway. The genes encoding P. simium DBP (PsDBPII) and simian DARC (sDARC) were sequenced from Southern brown howler monkeys (Alouatta guariba clamitans) naturally infected with P. simium because P. simium may also depend on the DBPII/DARC interaction. The sequences of DBP binding domains from P. vivax and P. simium were highly similar. However, the genetic variability of PsDBPII was lower than that of PvDBPII. Phylogenetic analyses demonstrated that these genes were strictly related and clustered in the same clade of the evolutionary tree. DARC from A. clamitans was also sequenced and contained three new non-synonymous substitutions. None of these substitutions were located in the N-terminal domain of DARC, which interacts directly with DBPII. The interaction between sDARC and PvDBPII was evaluated using a cytoadherence assay of COS7 cells expressing PvDBPII on their surfaces. Inhibitory binding assays in vitro demonstrated that antibodies from monkey sera blocked the interaction between COS-7 cells expressing PvDBPII and hDARC-positive erythrocytes. Taken together, phylogenetic analyses reinforced the hypothesis that the host switch from humans to monkeys may have occurred very recently in evolution, which sheds light on the evolutionary history of new world plasmodia. Further invasion studies would confirm whether P. simium depends on DBP/DARC to trigger internalization into red blood cells.

Antigenic variation

10.1371/journal.pone.0131339

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ANTIBODIES TO PLASMODIUM VIVAX APICAL MEMBRANE ANTIGEN 1: PERSISTENCE AND CORRELATION WITH MALARIA TRANSMISSION INTENSITY

American Journal of Tropical Medicine and Hygiene (2006)

Cristiane Guimarães Morais Irene S. Soares Luzia H. Carvalho Cor Jésus Fernandes Fontes Antoniana U. Krettli

The antibody responses to the apical membrane antigen 1 of the Plasmodium vivax (PvAMA-1) were investigated in subjects living in areas of Brazil with different levels of malaria transmission. The prevalence and the levels of IgG to PvAMA-1 increased with the time of exposure. The frequency of a positive response and the mean IgG level were higher in areas where malaria prevalence was more intense, especially among non-infected subjects exposed to moderate transmission over a period of 20 years. The proportions and levels of IgG1and IgG3 isotypes were significantly higher among those subjects with long-term exposure. Antibodies, mainly IgG1, to PvAMA-1 persisted for seven years among subjects briefly exposed to malaria in an outbreak outside the Brazilian malaria-endemic area. These data show the highly immunogenic properties of PvAMA-1 and emphasize its possible use as a malaria vaccine candidate.

Persistence (discontinuity)

10.4269/ajtmh.2006.75.582

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Citations (56)

Plasmodium simium/Plasmodium vivax infections in southern brown howler monkeys from the Atlantic Forest

Memórias do Instituto Oswaldo Cruz (2014)

Daniela Camargos Costa Vanessa Pecini da Cunha Gabriela Maíra Pereira de Assis Júlio César de Souza Zelinda Maria Braga Hirano

Blood infection by the simian parasite, Plasmodium simium, was identified in captive (n = 45, 4.4%) and in wild Alouatta clamitans monkeys (n = 20, 35%) from the Atlantic Forest of southern Brazil. A single malaria infection was symptomatic and the monkey presented clinical and haematological alterations. A high frequency of Plasmodium vivax-specific antibodies was detected among these monkeys, with 87% of the monkeys testing positive against P. vivax antigens. These findings highlight the possibility of malaria as a zoonosis in the remaining Atlantic Forest and its impact on the epidemiology of the disease.

Zoonosis

Plasmodium (life cycle)

Simian

Atlantic forest

10.1590/0074-0276130578

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Citations (32)

On the role of CD4+ T cells in the induction of malaria-specific CD8+ T cell response

Journal of tropical medicine and hygiene (2000)

Luzia H. Carvalho Julius Clemence R. Hafalla Gen‐ichiro Sano Fidel Zavala

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Plasmodium ovale malaria in Brazil: report of an imported case with a prolonged incubation period

The Journal of Infection in Developing Countries (2014)

Jean Ezequiel Limongi Daniela Camargos Costa Luzia H. Carvalho Iris Sousa Lopes Alcides Assis Silva

We report the first case of imported Plasmodium ovale in Brazil, confirmed using both conventional microscopy and PCR-based protocols. The patient was a 36-year-old Brazilian male who had been working as a miner in Cabinda Province, Angola. Based on his travel history, the parasite was dormant for at least two years. The relatively long period of incubation of P. ovale may obscure the link between exposure and disease. The recent increase in the number of people travelling to regions where P. ovale is endemic, suggests that a PCR-based protocol should be included as a complementary tool for malaria reference laboratories.

Plasmodium ovale

Incubation period

Plasmodium (life cycle)

10.3855/jidc.4037

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Citations (8)

Cross‐reactive cellular immune response to circumsporozoite proteins of Plasmodium vivax and P. falciparum in malaria‐exposed individuals

Parasite Immunology (1997)

Luzia H. Carvalho Cor Jésus Fernandes Fontes A. Fernandes H.C. MARINUZZI Antoniana U. Krettli

Acquired immunity against the recombinant circumsporozoite protein of P. falciparum (rPfCS) or P. vivax (rPvCS) was studied in two malarious areas of the Brazilian Amazon. Cellular responsiveness, evaluated by proliferative assays, was detected in about 45% of individuals who had recovered from recent acute malaria infections. Peripheral blood mononuclear cells of individuals whose last malaria infection was by P. vivax responded more to the rCS proteins than those who had P. falciparum . Since in P. vivax infections hypnozoites in the liver retain CS antigen, this stage may have contributed to the increased cellular response. The unexpected result was that in primoinfections by P. falciparum or P. vivax the proliferative response did not correspond to the rPfCS and rPvCS, respectively. Furthermore, among the malaria‐exposed individuals, there was a positive correlation between the intensity of the responses to the two rCS proteins. Our results suggest that cross‐reactive epitopes exist in the CS protein of P. falciparum and P. vivax . In the areas studied, the frequency of antibodies against rPvCS and/or rPfCS ranged from 43% to 11%. Species‐specific antibodies against the CS protein were detected in the primoinfected individuals. Some individuals living in the endemic area but with no clinical history of malaria were positive by serology (8%) or by in vitro proliferation (21%). However, antibodies and cellular responses against rCS were detected only in malaria‐exposed individuals, since those living outside the endemic area were all negative.

Circumsporozoite protein

Cellular immunity

10.1046/j.1365-3024.1997.d01-182.x

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Citations (14)

The role of pro-inflammatory cytokines IL-1 beta and IL-6 on proliferation of human hippocampal neural stem cells

Patricia A. Zunszain Christoph Anacker Luzia H. Carvalho Sandrine Thuret J. S. Price

BETA (programming language)

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Analysis of Genetic Variability of Plasmodium vivax Isolates from Different Brazilian Amazon Areas Using Tandem Repeats

American Journal of Tropical Medicine and Hygiene (2009)

Antônio Mauro Rezende Eduardo Tarazona‐Santos Álvaro D’ Almeida Couto Cor Jésus Fernandes Fontes José Maria de Souza

Few genetic markers have been described to analyze populations of Plasmodium vivax . The genetic variability of P. vivax has been analyzed mainly among isolates taken from areas ranging from hyper- to holoendemic areas. These studies of genetic variability have neglected many areas with different epidemiologic profiles. The purpose of this study was to analyze the genetic variability of P. vivax isolates from four different Brazilian Amazon areas. We chose to study the five most polymorphic tandem repeats (TRs) identified so far. All TRs studied were polymorphic in at least one studied population, with a modal allele at nearly all loci. Expected heterozygosity ranged from 0.462 to 0.666 and did not correlate with the repeat array length. The genetic distances among the populations varied from 0.027 to 0.241, and did not correlate with their geographic separation. Tandem repeats identified in P. vivax isolates failed to allow geographic clustering.

Genetic Variability

Population Genetics

10.4269/ajtmh.2009.80.729

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Citations (16)

Repression of NF-'KAPPA' activity and growth by glucocorticoids in ST1 glioma cells

Luzia H. Carvalho Hugo A. Armelin

Kappa

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Genetic variability and natural selection at the ligand domain of the Duffy binding protein in brazilian Plasmodium vivax populations

Malaria Journal (2010)

Taís Nóbrega de Sousa Eduardo Tarazona‐Santos Daniel J. Wilson Ana Paula Madureira Paula R. Kuser

Abstract Background Plasmodium 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 (PvDBP II ), which is the most variable segment of the protein. Methods To test whether diversifying natural selection has shaped the nucleotide diversity of PvDBP II 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 PvDBP II , and T- and B-cell epitopes were localized on the 3-D structure. Results The results suggest that: (i) recombination plays an important role in determining the haplotype structure of PvDBP II , and (ii) PvDBP II 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. Conclusions This study shows that some polymorphisms of PvDBP II 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.

Negative selection

10.1186/1475-2875-9-334

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Citations (38)