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[PMID]: 29244851 [Au] Autor: Leitgeb AM; Charunwatthana P; Rueangveerayut R; Uthaisin C; Silamut K; Chotivanich K; Sila P; Moll K; Lee SJ; Lindgren M; Holmer E; Färnert A; Kiwuwa MS; Kristensen J; Herder C; Tarning J; Wahlgren M; Dondorp AM [Ad] Endereço: Modus Therapeutics AB, Stockholm, Sweden. [Ti] Título: Inhibition of merozoite invasion and transient de-sequestration by sevuparin in humans with Plasmodium falciparum malaria. [So] Source: PLoS One;12(12):e0188754, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: SEVERE MALARIA: Even with the best available treatment, the mortality from severe Plasmodium falciparum malaria remains high. Typical features at death are high parasite loads and obstructed micro- vasculature. Infected erythrocytes (IE) containing mature parasites bind to the host receptor heparan sulfate, which is also an important receptor for merozoite invasion. To block merozoite invasion has not previously been proposed as an adjunctive therapeutic approach but it may preclude the early expansion of an infection that else leads to exacerbated sequestration and death. SEVUPARIN IN PHASE I STUDY: The drug sevuparin was developed from heparin because heparan sulfate and heparin are nearly identical, so the rationale was that sevuparin would act as a decoy receptor during malaria infection. A phase I study was performed in healthy male volunteers and sevuparin was found safe and well tolerated. SEVUPARIN IN PHASE I/II CLINICAL STUDY: A phase I/II clinical study was performed in which sevuparin was administered via short intravenous infusions to malaria patients with uncomplicated malaria who were also receiving atovaquone/proguanil treatment. This was a Phase I/II, randomized, open label, active control, parallel assignment study. Sevuparin was safe and well tolerated in the malaria patients. The mean relative numbers of ring-stage IEs decreased after a single sevuparin infusion and mature parasite IEs appeared transiently in the circulation. The effects observed on numbers of merozoites and throphozoites in the circulation, were detected already one hour after the first sevuparin injection. Here we report the development of a candidate drug named sevuparin that both blocks merozoite invasion and transiently de-sequesters IE in humans with P. falciparum malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT01442168. [Mh] Termos MeSH primário: Antimaláricos/farmacologia Atovaquona/farmacologia Heparina/análogos & derivados Malária Falciparum/tratamento farmacológico Merozoítos/efeitos dos fármacos Parasitemia/tratamento farmacológico Plasmodium falciparum/efeitos dos fármacos Proguanil/farmacologia [Mh] Termos MeSH secundário: Administração Oral Adolescente Adulto Idoso Antimaláricos/sangue Antimaláricos/farmacocinética Área Sob a Curva Atovaquona/sangue Atovaquona/farmacocinética Ligação Competitiva Esquema de Medicação Combinação de Medicamentos Quimioterapia Combinada Eritrócitos/efeitos dos fármacos Eritrócitos/parasitologia Feminino Heparina/sangue Heparina/farmacocinética Heparina/farmacologia Heparitina Sulfato/química Heparitina Sulfato/metabolismo Seres Humanos Infusões Intravenosas Malária Falciparum/sangue Malária Falciparum/parasitologia Masculino Merozoítos/fisiologia Meia-Idade Carga Parasitária Parasitemia/sangue Parasitemia/parasitologia Plasmodium falciparum/fisiologia Proguanil/sangue Proguanil/farmacocinética Índice de Gravidade de Doença [Pt] Tipo de publicação: CLINICAL TRIAL, PHASE I; CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL [Nm] Nome de substância: 0 (Antimalarials); 0 (Drug Combinations); 0 (atovaquone, proguanil drug combination); 0 (sevuparin); 9005-49-6 (Heparin); 9050-30-0 (Heparitin Sulfate); S61K3P7B2V (Proguanil); Y883P1Z2LT (Atovaquone) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180207 [Lr] Data última revisão: 180207 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171216 [Cl] Clinical Trial: ClinicalTrial [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0188754

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[PMID]: 28922424 [Au] Autor: Hopp CS; Bennett BL; Mishra S; Lehmann C; Hanson KK; Lin JW; Rousseau K; Carvalho FA; van der Linden WA; Santos NC; Bogyo M; Khan SM; Heussler V; Sinnis P [Ad] Endereço: Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. [Ti] Título: Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites. [So] Source: PLoS Pathog;13(9):e1006586, 2017 Sep. [Is] ISSN: 1553-7374 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Proteases have been implicated in a variety of developmental processes during the malaria parasite lifecycle. In particular, invasion and egress of the parasite from the infected hepatocyte and erythrocyte, critically depend on protease activity. Although falcipain-1 was the first cysteine protease to be characterized in P. falciparum, its role in the lifecycle of the parasite has been the subject of some controversy. While an inhibitor of falcipain-1 blocked erythrocyte invasion by merozoites, two independent studies showed that falcipain-1 disruption did not affect growth of blood stage parasites. To shed light on the role of this protease over the entire Plasmodium lifecycle, we disrupted berghepain-1, its ortholog in the rodent parasite P. berghei. We found that this mutant parasite displays a pronounced delay in blood stage infection after inoculation of sporozoites. Experiments designed to pinpoint the defect of berghepain-1 knockout parasites found that it was not due to alterations in gliding motility, hepatocyte invasion or liver stage development and that injection of berghepain-1 knockout merosomes replicated the phenotype of delayed blood stage growth after sporozoite inoculation. We identified an additional role for berghepain-1 in preparing blood stage merozoites for infection of erythrocytes and observed that berghepain-1 knockout parasites exhibit a reticulocyte restriction, suggesting that berghepain-1 activity broadens the erythrocyte repertoire of the parasite. The lack of berghepain-1 expression resulted in a greater reduction in erythrocyte infectivity in hepatocyte-derived merozoites than it did in erythrocyte-derived merozoites. These observations indicate a role for berghepain-1 in processing ligands important for merozoite infectivity and provide evidence supporting the notion that hepatic and erythrocytic merozoites, though structurally similar, are not identical. [Mh] Termos MeSH primário: Cisteína Endopeptidases/metabolismo Hepatócitos/metabolismo Malária/metabolismo Merozoítos/metabolismo Plasmodium falciparum/metabolismo [Mh] Termos MeSH secundário: Animais Inibidores de Cisteína Proteinase/farmacologia Eritrócitos/parasitologia Hepatócitos/parasitologia Fígado/metabolismo Malária/parasitologia Plasmodium falciparum/genética Proteínas de Protozoários/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cysteine Proteinase Inhibitors); 0 (Protozoan Proteins); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.- (falcipain) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171017 [Lr] Data última revisão: 171017 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170919 [St] Status: MEDLINE [do] DOI: 10.1371/journal.ppat.1006586

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[PMID]: 28834337 [Au] Autor: Chenette EJ [Ad] Endereço: The FEBS Journal, Editorial Office, Cambridge, UK. [Ti] Título: Recent buzz in malaria research. [So] Source: FEBS J;284(16):2556-2559, 2017 Aug. [Is] ISSN: 1742-4658 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: In this Commentary, we highlight the latest findings in three active areas of malaria research: Plasmodium biology; host response; and malaria control, prevention and treatment. [Mh] Termos MeSH primário: Pesquisa Biomédica Malária/parasitologia Malária/transmissão Plasmodium/fisiologia [Mh] Termos MeSH secundário: Animais Pesquisa Biomédica/tendências Interações Hospedeiro-Parasita Seres Humanos Malária/metabolismo Merozoítos/citologia Merozoítos/fisiologia Modelos Biológicos [Pt] Tipo de publicação: JOURNAL ARTICLE [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171002 [Lr] Data última revisão: 171002 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170824 [St] Status: MEDLINE [do] DOI: 10.1111/febs.14160

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[PMID]: 28698207 [Au] Autor: Kosaisavee V; Suwanarusk R; Chua ACY; Kyle DE; Malleret B; Zhang R; Imwong M; Imerbsin R; Ubalee R; Sámano-Sánchez H; Yeung BKS; Ong JJY; Lombardini E; Nosten F; Tan KSW; Bifani P; Snounou G; Rénia L; Russell B [Ad] Endereço: Department of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok, Thailand. [Ti] Título: Strict tropism for CD71 /CD234 human reticulocytes limits the zoonotic potential of . [So] Source: Blood;130(11):1357-1363, 2017 Sep 14. [Is] ISSN: 1528-0020 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Two malaria parasites of Southeast Asian macaques, and , can infect humans experimentally. In Malaysia, where both species are common, zoonotic knowlesi malaria has recently become dominant, and cases are recorded throughout the region. By contrast, to date, only a single case of naturally acquired has been found in humans. In this study, we show that whereas merozoites invade monkey red blood cells indiscriminately in vitro, in humans, they are restricted to reticulocytes expressing both transferrin receptor 1 (Trf1 or CD71) and the Duffy antigen/chemokine receptor (DARC or CD234). This likely contributes to the paucity of detectable zoonotic cynomolgi malaria. We further describe postinvasion morphologic and rheologic alterations in -infected human reticulocytes that are strikingly similar to those observed for These observations stress the value of as a model in the development of blood stage vaccines against vivax malaria. [Mh] Termos MeSH primário: Antígenos CD/metabolismo Sistema do Grupo Sanguíneo Duffy/metabolismo Plasmodium cynomolgi/fisiologia Receptores de Superfície Celular/metabolismo Receptores da Transferrina/metabolismo Reticulócitos/parasitologia Tropismo Zoonoses/parasitologia [Mh] Termos MeSH secundário: Animais Eritrócitos/parasitologia Interações Hospedeiro-Parasita Seres Humanos Macaca Merozoítos/fisiologia Plasmodium vivax/fisiologia Reologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antigens, CD); 0 (CD71 antigen); 0 (DARC protein, human); 0 (Duffy Blood-Group System); 0 (Receptors, Cell Surface); 0 (Receptors, Transferrin) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171008 [Lr] Data última revisão: 171008 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170713 [St] Status: MEDLINE [do] DOI: 10.1182/blood-2017-02-764787

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[PMID]: 28555954 [Au] Autor: Swilks E; Jenkins C; Poynting A; Collins D; Krebs GL [Ad] Endereço: School of Animal and Veterinary Sciences, Charles Sturt University, Locked Bag 588, Wagga Wagga, New South Wales 2678, Australia. [Ti] Título: Prevalence and effect of Theileria orientalis infection in homebred calves in the Gloucester region of New South Wales, Australia. [So] Source: Aust Vet J;95(6):211-216, 2017 Jun. [Is] ISSN: 1751-0813 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: OBJECTIVES: To examine the prevalence of Theileria orientalis in the Gloucester area of New South Wales and its effect on individual animals. METHODS: Blood samples (EDTA and clotted blood) were collected from a total of 55 calves and their dams from 6 properties over a 16-week period. A total of 202 and 190 blood samples were collected from the calves and dams, respectively, and were examined via blood film for the presence of intraerythrocytic T. orientalis piroplasms. Packed cell volume (PCV) was measured to determine infection resulting in anaemia. The presence of antibodies against the T. orientalis major piroplasm surface protein (MPSP) was tested using ELISA. RESULTS: The overall prevalence of T. orientalis infection in both dams and calves from all herds examined was 95%. Mean peak parasitaemia was observed in calves between 6 and 9 weeks of age (P = 0.051), coinciding with a decline in mean PCV. Only 3 (6%) of the blood samples collected from the dams were positive for Theileria-associated antibodies and no significant relationship (P > 0.05) was found between the presence of antibodies in the dams and PCV levels in the calves. There was no evidence that passive transfer of antibodies from dams to calves protected the calves against a decline in PCV. CONCLUSION: This study confirmed a high prevalence of low-level Theileria infection, but low MPSP seroconversion rates, in dams and calves in an area where the disease has been endemic for a number of years. [Mh] Termos MeSH primário: Doenças dos Bovinos/epidemiologia Doenças dos Bovinos/parasitologia Theileriose/epidemiologia [Mh] Termos MeSH secundário: Anemia/epidemiologia Anemia/parasitologia Anemia/veterinária Animais Anticorpos Antiprotozoários/sangue Bovinos Doenças dos Bovinos/sangue Ensaio de Imunoadsorção Enzimática/veterinária Feminino Masculino Merozoítos New South Wales/epidemiologia Reação em Cadeia da Polimerase/veterinária Prevalência Theileria/genética Theileria/imunologia Theileriose/sangue Theileriose/complicações [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies, Protozoan) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171006 [Lr] Data última revisão: 171006 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170531 [St] Status: MEDLINE [do] DOI: 10.1111/avj.12593

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[PMID]: 28484054 [Au] Autor: Kennedy AT; Wijeyewickrema LC; Huglo A; Lin C; Pike R; Cowman AF; Tham WH [Ad] Endereço: Infection and Immunity Division, The Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia. [Ti] Título: Recruitment of Human C1 Esterase Inhibitor Controls Complement Activation on Blood Stage Merozoites. [So] Source: J Immunol;198(12):4728-4737, 2017 Jun 15. [Is] ISSN: 1550-6606 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The complement system is a front-line defense system that opsonizes and lyses invading pathogens. To survive, microbes exposed to serum must evade the complement response. To achieve this, many pathogens recruit soluble human complement regulators to their surfaces and hijack their regulatory function for protection from complement activation. C1 esterase inhibitor (C1-INH) is a soluble regulator of complement activation that negatively regulates the classical and lectin pathways of complement to protect human tissue from aberrant activation. In this article, we show that merozoites, the invasive form of blood stage malaria parasites, actively recruit C1-INH to their surfaces when exposed to human serum. We identified MSP3.1, a member of the merozoite surface protein 3 family of merozoite surface proteins, as the direct interaction partner. When bound to the merozoite surface, C1-INH retains its ability to complex with and inhibit C1s, MASP1, and MASP2, the activating proteases of the complement cascade. merozoites that lack MSP3.1 showed a marked reduction in C1-INH recruitment and increased C3b deposition on their surfaces. However, these Δ MSP3.1 merozoites exhibit enhanced invasion of RBCs in the presence of active complement. This study characterizes an immune-evasion strategy used by malaria parasites and highlights the complex relationship between merozoites and the complement system. [Mh] Termos MeSH primário: Antígenos de Protozoários/metabolismo Ativação do Complemento Proteína Inibidora do Complemento C1/metabolismo Evasão da Resposta Imune Proteínas de Membrana/metabolismo Merozoítos/imunologia Plasmodium falciparum/imunologia [Mh] Termos MeSH secundário: Antígenos de Protozoários/imunologia Proteína Inibidora do Complemento C1/genética Complemento C1s/antagonistas & inibidores Complemento C1s/imunologia Complemento C1s/metabolismo Eritrócitos/parasitologia Seres Humanos Serina Proteases Associadas a Proteína de Ligação a Manose/antagonistas & inibidores Serina Proteases Associadas a Proteína de Ligação a Manose/imunologia Serina Proteases Associadas a Proteína de Ligação a Manose/metabolismo Proteínas de Membrana/imunologia Merozoítos/química Plasmodium falciparum/crescimento & desenvolvimento Plasmodium falciparum/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antigens, Protozoan); 0 (Complement C1 Inhibitor Protein); 0 (Membrane Proteins); EC 3.4.21.- (MASP1 protein, human); EC 3.4.21.- (MASP2 protein, human); EC 3.4.21.- (Mannose-Binding Protein-Associated Serine Proteases); EC 3.4.21.42 (Complement C1s) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170927 [Lr] Data última revisão: 170927 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170510 [St] Status: MEDLINE [do] DOI: 10.4049/jimmunol.1700067

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[PMID]: 28372843 [Au] Autor: Chaney SB; Marsh AE; Lewis S; Carman M; Howe DK; Saville WJ; Reed SM [Ad] Endereço: Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, 43210, United States. [Ti] Título: Sarcocystis neurona manipulation using culture-derived merozoites for bradyzoite and sporocyst production. [So] Source: Vet Parasitol;238:35-42, 2017 Apr 30. [Is] ISSN: 1873-2550 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Equine protozoal myeloencephalitis (EPM) remains a significant central nervous system disease of horses in the American continents. Sarcocystis neurona is considered the primary causative agent and its intermediate life stages are carried by a wide host-range including raccoons (Procyon lotor) in North America. S. neurona sarcocysts mature in raccoon skeletal muscle and can produce central nervous system disease in raccoons, mirroring the clinical presentation in horses. The study aimed to develop laboratory tools whereby the life cycle and various life stages of S. neurona could be better studied and manipulated using in vitro and in vivo systems and compare the biology of two independent isolates. This study utilized culture-derived parasites from S. neurona strains derived from a raccoon or from a horse to initiate raccoon infections. Raccoon tissues, including fresh and cryopreserved tissues, were used to establish opossum (Didelphis virginiana) infections, which then shed sporocyts with retained biological activity to cause encephalitis in mice. These results demonstrate that sarcocysts can be generated using in vitro-derived S. neurona merozoites, including an isolate originally derived from a naturally infected horse with clinical EPM. This study indicates the life cycle can be significantly manipulated in the laboratory without affecting subsequent stage development, allowing further purification of strains and artificial maintenance of the life cycle. [Mh] Termos MeSH primário: Merozoítos/fisiologia Oocistos/fisiologia Guaxinins/parasitologia Sarcocystis/fisiologia Sarcocistose/veterinária [Mh] Termos MeSH secundário: Animais Criopreservação Camundongos Músculo Esquelético/parasitologia Sarcocistose/parasitologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171030 [Lr] Data última revisão: 171030 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170405 [St] Status: MEDLINE

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[PMID]: 28361273 [Au] Autor: Gong Z; Yin H; Ma X; Liu B; Han Z; Gou L; Cai J [Ad] Endereço: State Key Laboratory of Veterinary Etiological Biology; Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Science, Lanzhou, Gansu Province, 730046, People's Republic of China. [Ti] Título: Widespread 5-methylcytosine in the genomes of avian Coccidia and other apicomplexan parasites detected by an ELISA-based method. [So] Source: Parasitol Res;116(5):1573-1579, 2017 May. [Is] ISSN: 1432-1955 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: To date, little is known about cytosine methylation in the genomic DNA of apicomplexan parasites, although it has been confirmed that this important epigenetic modification exists in many lower eukaryotes, plants, and animals. In the present study, ELISA-based detection demonstrated that low levels of 5-methylcytosine (5-mC) are present in Eimeria spp., Toxoplasma gondii, Cryptosporidium spp., and Neospora caninum. The proportions of 5-mC in genomic DNA were 0.18 ± 0.02% in E tenella sporulated oocysts, 0.19 ± 0.01% in E. tenella second-generation merozoites, 0.22 ± 0.04% in T. gondii tachyzoites, 0.28 ± 0.03% in N. caninum tachyzoites, and 0.06 ± 0.01, 0.11 ± 0.01, and 0.09 ± 0.01% in C. andersoni, C. baileyi, and C. parvum sporulated oocysts, respectively. In addition, we found that the percentages of 5-mC in E. tenella varied considerably at different life stages, with sporozoites having the highest percentage of 5-mC (0.78 ± 0.10%). Similar stage differences in 5-mC were also found in E. maxima, E. necatrix, and E. acervulina, the levels of 5-mC in their sporozoites being 4.3-, 1.8-, 2.5-, and 2.0-fold higher than that of sporulated oocysts, respectively (p < 0.01). Furthermore, a total DNA methyltransferase-like activity was detected in whole cell extracts prepared from E. tenella sporozoites. In conclusion, genomic DNA methylation is present in these apicomplexan parasites and may play a role in the stage conversion of Eimeria. [Mh] Termos MeSH primário: 5-Metilcitosina/análise Galinhas/parasitologia Coccidiose/veterinária Cryptosporidium/genética DNA de Protozoário/genética Eimeria tenella/genética Neospora/genética Toxoplasma/genética [Mh] Termos MeSH secundário: Animais Coccidiose/parasitologia Metilação de DNA/genética Ensaio de Imunoadsorção Enzimática Merozoítos/citologia Oocistos/citologia Esporozoítos/citologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (DNA, Protozoan); 6R795CQT4H (5-Methylcytosine) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 171007 [Lr] Data última revisão: 171007 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170401 [St] Status: MEDLINE [do] DOI: 10.1007/s00436-017-5434-x

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[PMID]: 28351409 [Au] Autor: Muh F; Han JH; Nyunt MH; Lee SK; Jeon HY; Ha KS; Park WS; Hong SH; Ahmed MA; Na S; Takashima E; Tsuboi T; Han ET [Ad] Endereço: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea. [Ti] Título: Identification of a novel merozoite surface antigen of Plasmodium vivax, PvMSA180. [So] Source: Malar J;16(1):133, 2017 Mar 28. [Is] ISSN: 1475-2875 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: Although a number of Plasmodium vivax proteins have been identified, few have been investigated as potential vaccine candidates. This study characterized the Plasmodium vivax merozoite surface antigen 180 (PvMSA180, PVX_094920), a novel P. vivax antigenic protein. METHODS: The target gene was amplified as four overlapping domains (D1, D2, D3 and D4) to enable expression of the recombinant protein using cell-free and bacterial expression systems. The recombinant PvMSA180 proteins were used in protein microarrays to evaluate the humoral immune response of 72 vivax-infected patients and 24 vivax-naïve individuals. Antibodies produced in mice against the PvMSA180-D1 and -D4 domains were used to assess the subcellular localization of schizont-stage parasites with immunofluorescence assays. A total of 51 pvmsa180 sequences from 12 countries (41 sequences from PlasmoDB and 6 generated in this study) were used to determine the genetic diversity and genealogical relationships with DNAsp and NETWORK software packages, respectively. RESULTS: PvMSA180 consists of 1603 amino acids with a predicted molecular mass of 182 kDa, and has a signal peptide at the amino-terminus. A total of 70.8% of patients (51/72) showed a specific antibody response to at least one of the PvMSA180 domains, and 20.8% (15/72) exhibited a robust antibody response to at least three of the domains. These findings suggest that PvMSA180 is targeted by the humoral immune response during natural infection with P. vivax. Immunofluorescence analysis demonstrated that PvMSA180 is localized on the merozoite surface of schizont-stage parasites, and pvmsa180 sequences originating from various geographic regions worldwide showed low genetic diversity. Twenty-two haplotypes were found, and haplotype 6 (Hap_6, 77%) of pvmsa180 was detected in isolates from six countries. CONCLUSIONS: A novel P. vivax surface protein, PvMSA180, was characterized in this study. Most of P. vivax-infected patients had specific antibodies against particular antigenic domains, indicating that this protein is immunogenic in naturally exposed populations. Genetic analysis of worldwide isolates showed that pvmsa180 is less polymorphic than other well-known candidates and that some haplotypes are common to several countries. However, additional studies with a larger sample size are necessary to evaluate the antibody responses in geographically separated populations, and to identify the function of PvMSA180 during parasite invasion. [Mh] Termos MeSH primário: Antígenos de Protozoários/análise Antígenos de Superfície/análise Merozoítos/química Plasmodium vivax/química [Mh] Termos MeSH secundário: Adolescente Adulto Animais Anticorpos Antiprotozoários/sangue Antígenos de Protozoários/química Antígenos de Protozoários/genética Antígenos de Protozoários/imunologia Antígenos de Superfície/química Antígenos de Superfície/genética Antígenos de Superfície/imunologia Feminino Variação Genética Seres Humanos Masculino Merozoítos/imunologia Camundongos Endogâmicos BALB C Microscopia de Fluorescência Peso Molecular Filogeografia Plasmodium vivax/imunologia Sinais Direcionadores de Proteínas/genética Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies, Protozoan); 0 (Antigens, Protozoan); 0 (Antigens, Surface); 0 (Protein Sorting Signals) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170606 [Lr] Data última revisão: 170606 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170330 [St] Status: MEDLINE [do] DOI: 10.1186/s12936-017-1760-9

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[PMID]: 28329101 [Au] Autor: Kana IH; Adu B; Tiendrebeogo RW; Singh SK; Dodoo D; Theisen M [Ad] Endereço: Department for Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark [Ti] Título: Naturally Acquired Antibodies Target the Glutamate-Rich Protein on Intact Merozoites and Predict Protection Against Febrile Malaria. [So] Source: J Infect Dis;215(4):623-630, 2017 02 15. [Is] ISSN: 1537-6613 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Background: Plasmodium species antigens accessible at the time of merozoite release are likely targets of biologically functional antibodies. Methods: Immunoglobulin G (IgG) antibodies against intact merozoites were quantified in the plasma of Ghanaian children from a longitudinal cohort using a novel flow cytometry-based immunofluorescence assay. Functionality of these antibodies, as well as glutamate-rich protein (GLURP)-specific affinity-purified IgG from malaria hyperimmune Liberian adults, was assessed by the opsonic phagocytosis (OP) assay. Results: Opsonic phagocytosis activity was strongly associated (hazard ratio [HR] = 0.46; 95% confidence interval [CI] = .30-.73; P = .0008) with protection against febrile malaria. Of the antimerozoite-specific antibodies, only IgG3 was significantly associated with both OP and protection (HR = 0.53; 95% CI = .34-.84; Pcorrected = .03) against febrile malaria. Similarly, GLURP-specific antibodies previously shown to be protective against febrile malaria in this same cohort were significantly associated with OP activity in this study. GLURP-specific antibodies recognized merozoites and also mediated OP activity. Conclusions: These findings support previous studies that found OP of merozoites to be associated with protection against malaria and further shows IgG3 and GLURP antibodies are key in the OP mechanism, thus giving further impetus for the development of malaria vaccines targeting GLURP. [Mh] Termos MeSH primário: Anticorpos Antiprotozoários/imunologia Malária/imunologia Proteínas de Protozoários/imunologia [Mh] Termos MeSH secundário: Anticorpos Antiprotozoários/sangue Antígenos de Protozoários/sangue Criança Pré-Escolar Estudos de Coortes Febre/imunologia Seguimentos Gana Seres Humanos Imunoglobulina G/sangue Imunoglobulina G/imunologia Lactente Modelos Logísticos Estudos Longitudinais Merozoítos/imunologia Fagocitose Plasmodium falciparum/imunologia Modelos de Riscos Proporcionais Proteínas de Protozoários/sangue [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies, Protozoan); 0 (Antigens, Protozoan); 0 (Immunoglobulin G); 0 (Protozoan Proteins); 145112-81-8 (glutamate-rich protein, Plasmodium) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170615 [Lr] Data última revisão: 170615 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170323 [St] Status: MEDLINE [do] DOI: 10.1093/infdis/jiw617

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