Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.749
Filtrar
1.
Front Immunol ; 12: 565625, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679730

RESUMO

Sub-Saharan Africa has generally experienced few cases and deaths of coronavirus disease 2019 (COVID-19). In addition to other potential explanations for the few cases and deaths of COVID-19 such as the population socio-demographics, early lockdown measures and the possibility of under reporting, we hypothesize in this mini review that individuals with a recent history of malaria infection may be protected against infection or severe form of COVID-19. Given that both the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium falciparum (P. falciparum) merozoites bind to the cluster of differentiation 147 (CD147) immunoglobulin, we hypothesize that the immunological memory against P. falciparum merozoites primes SARS-CoV-2 infected cells for early phagocytosis, hence protecting individuals with a recent P. falciparum infection against COVID-19 infection or severity. This mini review therefore discusses the potential biological link between P. falciparum infection and COVID-19 infection or severity and further highlights the importance of CD147 immunoglobulin as an entry point for both SARS-CoV-2 and P. falciparum into host cells.


Assuntos
Basigina/imunologia , Memória Imunológica , Malária Falciparum , Plasmodium falciparum/imunologia , /imunologia , África ao Sul do Saara/epidemiologia , /imunologia , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Merozoítos/imunologia , Índice de Gravidade de Doença
2.
Malar J ; 20(1): 124, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653360

RESUMO

BACKGROUND: Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. METHODS: 153 blood spot samples from Bioko malaria patients were collected during 2016-2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. RESULTS: A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN-dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure. CONCLUSIONS: Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.


Assuntos
Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Epitopos , Guiné Equatorial/epidemiologia , Frequência do Gene , Variação Genética , Haplótipos , Humanos , Vacinas Antimaláricas , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Polimorfismo Genético , Proteínas de Protozoários/química , Proteínas de Protozoários/imunologia , Seleção Genética
3.
Nat Commun ; 12(1): 1750, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741942

RESUMO

Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites. Among nine Pfs230 human monoclonal antibodies (mAbs) that we generated, one potently blocks transmission to mosquitoes in a complement-dependent manner and reacts to the gamete surface; the other eight show only low or no blocking activity. The structure of the transmission-blocking mAb in complex with vaccine antigen reveals a large discontinuous conformational epitope, specific to domain 1 of Pfs230 and comprising six structural elements in the protein. The epitope is conserved, suggesting the transmission-blocking mAb is broadly functional. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination.


Assuntos
Anticorpos Monoclonais/farmacologia , Anticorpos Antiprotozoários/farmacologia , Epitopos/imunologia , Células Germinativas/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/efeitos dos fármacos , Adulto , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/química , Antígenos de Protozoários/imunologia , Sítios de Ligação , Células Cultivadas , Epitopos/química , Interações Hospedeiro-Parasita/efeitos dos fármacos , Interações Hospedeiro-Parasita/imunologia , Humanos , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/imunologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Mosquitos Vetores/parasitologia , Plasmodium falciparum/imunologia , Plasmodium falciparum/fisiologia , Conformação Proteica , Proteínas de Protozoários/química , Proteínas de Protozoários/imunologia
4.
Nat Commun ; 12(1): 1742, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741975

RESUMO

A highly protective vaccine will greatly facilitate achieving and sustaining malaria elimination. Understanding mechanisms of antibody-mediated immunity is crucial for developing vaccines with high efficacy. Here, we identify key roles in humoral immunity for Fcγ-receptor (FcγR) interactions and opsonic phagocytosis of sporozoites. We identify a major role for neutrophils in mediating phagocytic clearance of sporozoites in peripheral blood, whereas monocytes contribute a minor role. Antibodies also promote natural killer cell activity. Mechanistically, antibody interactions with FcγRIII appear essential, with FcγRIIa also required for maximum activity. All regions of the circumsporozoite protein are targets of functional antibodies against sporozoites, and N-terminal antibodies have more activity in some assays. Functional antibodies are slowly acquired following natural exposure to malaria, being present among some exposed adults, but uncommon among children. Our findings reveal targets and mechanisms of immunity that could be exploited in vaccine design to maximize efficacy.


Assuntos
Imunidade Humoral , Malária/imunologia , Malária/prevenção & controle , Receptores de IgG/imunologia , Esporozoítos/imunologia , Adulto , Idoso , Anticorpos Antiprotozoários/imunologia , Criança , Feminino , Humanos , Quênia , Vacinas Antimaláricas/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Neutrófilos/imunologia , Fagocitose/imunologia , Plasmodium falciparum/imunologia , Receptores de IgG/metabolismo , Células THP-1 , Adulto Jovem
5.
Nat Commun ; 12(1): 1063, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594061

RESUMO

The most advanced P. falciparum circumsporozoite protein-based malaria vaccine, RTS,S/AS01 (RTS,S), confers partial protection but with antibody titers that wane relatively rapidly, highlighting the need to elicit more potent and durable antibody responses. Here, we elucidate crystal structures, binding affinities and kinetics, and in vivo protection of eight anti-NANP antibodies derived from an RTS,S phase 2a trial and encoded by three different heavy-chain germline genes. The structures reinforce the importance of homotypic Fab-Fab interactions in protective antibodies and the overwhelmingly dominant preference for a germline-encoded aromatic residue for recognition of the NANP motif. In this study, antibody apparent affinity correlates best with protection in an in vivo mouse model, with the more potent antibodies also recognizing epitopes with repeating secondary structural motifs of type I ß- and Asn pseudo 310 turns; such insights can be incorporated into design of more effective immunogens and antibodies for passive immunization.


Assuntos
Anticorpos Antiprotozoários/imunologia , Malária Falciparum/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Sequências Repetitivas de Aminoácidos , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Afinidade de Anticorpos/imunologia , Cristalografia por Raios X , Epitopos/química , Epitopos/imunologia , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/imunologia , Cinética , Camundongos Endogâmicos C57BL , Modelos Moleculares , Parasitos/imunologia , Peptídeos/química , Peptídeos/metabolismo , Ligação Proteica
6.
J Leukoc Biol ; 109(1): 77-90, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33617048

RESUMO

B cells play a central role in antiviral and antiparasitic immunity, not only as producers of antibodies, but also as APCs and mediators of inflammation. In this study, we used 16-color flow cytometry analysis to investigate the frequency, differentiation, and activation status of peripheral B cells of patients with SARS-CoV-2 infection or acute Plasmodium falciparum malaria compared with the healthy individuals. As a main result, we observed an increase of the frequency of (CD27-, CD21-) atypical memory B cells and (CD19+, CD27+, CD38+) plasmablasts in malaria and COVID-19 patients. Additionally, CD86, PD-1, CXCR3, and CD39 expression was up-regulated, whereas CD73 was down-regulated on plasmablasts of COVID-19 and malaria patients compared with the bulk B cell population. In particular, there was a more pronounced loss of CD73+ B cells in malaria. The frequency of plasmablasts positively correlated with serum levels of CRP, IL-6, and LDH of COVID-19 patients. In the longitudinal course of COVID-19, a rapid normalization of the frequency of atypical memory B cells was observed. The role and function of plasmablasts and atypical memory B cells in COVID-19 and other acute infections remain to be further investigated. The role of B cells as either "driver or passenger" of hyperinflammation during COVID-19 needs to be clarified.


Assuntos
/imunologia , Memória Imunológica , Malária Falciparum/imunologia , Plasmócitos/imunologia , Plasmodium falciparum/imunologia , /imunologia , Adulto , Idoso , Antígenos CD/imunologia , Feminino , Humanos , Malária Falciparum/patologia , Masculino , Pessoa de Meia-Idade , Plasmócitos/patologia
7.
PLoS One ; 15(12): e0243943, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33332459

RESUMO

Developing a vaccine against Plasmodium falciparum malaria has been challenging, primarily due to high levels of antigen polymorphism and a complex parasite lifecycle. Immunization with the P. falciparum merozoite antigens PfMSRP5, PfSERA9, PfRAMA, PfCyRPA and PfRH5 has been shown to give rise to growth inhibitory and synergistic antisera. Therefore, these five merozoite proteins are considered to be promising candidates for a second-generation multivalent malaria vaccine. Nevertheless, little is known about IgG and IgM responses to these antigens in populations that are naturally exposed to P. falciparum. In this study, serum samples from clinically immune adults and malaria exposed children from Ghana were studied to compare levels of IgG and IgM specific for PfMSRP5, PfSERA9, PfRAMA, PfCyRPA and PfRH5. All five antigens were found to be specifically recognized by both IgM and IgG in serum from clinically immune adults and from children with malaria. Longitudinal analysis of the latter group showed an early, transient IgM response that was followed by IgG, which peaked 14 days after the initial diagnosis. IgG levels and parasitemia did not correlate, whereas parasitemia was weakly positively correlated with IgM levels. These findings show that IgG and IgM specific for merozoite antigens PfMSRP5, PfSERA9, PfRAMA, PfCyRPA and PfRH5 are high in children during P. falciparum malaria, but that the IgM induction and decline occurs earlier in infection than that of IgG.


Assuntos
Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Adolescente , Adulto , Idoso , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Vacinas Antimaláricas/imunologia , Malária Falciparum/parasitologia , Masculino , Merozoítos/imunologia , Merozoítos/patogenicidade , Pessoa de Meia-Idade , Plasmodium falciparum/patogenicidade , Adulto Jovem
8.
PLoS One ; 15(12): e0244457, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382787

RESUMO

BACKGROUND: Plasmodium falciparum histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs) are exclusively recommended for malaria diagnosis in Uganda; however, their functionality can be affected by parasite-related factors that have not been investigated in field settings. METHODS: Using a cross-sectional design, we analysed 219 RDT-/microscopy+ and 140 RDT+/microscopy+ dried blood spots obtained from symptomatic children aged 2-10 years from 48 districts in Uganda between 2017 and 2019. We aimed to investigate parasite-related factors contributing to false RDT results by molecular characterization of parasite isolates. ArcGIS software was used to map the geographical distribution of parasites. Statistical analysis was performed using chi-square or Fisher's exact tests, with P ≤ 0.05 indicating significance. Odds ratios (ORs) were used to assess associations, while logistic regression was performed to explore possible factors associated with false RDT results. RESULTS: The presence of parasite DNA was confirmed in 92.5% (332/359) of the blood samples. The levels of agreement between the HRP2 RDT and PCR assay results in the (RDT+/microscopy+) and (RDT-/microscopy+) sample subsets were 97.8% (137/140) and 10.9% (24/219), respectively. Factors associated with false-negative RDT results in the (RDT-/microscopy+) samples were parasite density (<1,000/µl), pfhrp2/3 gene deletion and non-P. falciparum species (aOR 2.65, 95% CI: 1.62-4.38, P = 0.001; aOR 4.4, 95% CI 1.72-13.66, P = 0.004; and aOR 18.65, 95% CI: 5.3-38.7, P = 0.001, respectively). Overall, gene deletion and non-P. falciparum species contributed to 12.3% (24/195) and 19.0% (37/195) of false-negative RDT results, respectively. Of the false-negative RDTs results, 80.0% (156/195) were from subjects with low-density infections (< 25 parasites per 200 WBCs or <1,000/µl). CONCLUSION: This is the first evaluation and report of the contributions of pfhrp2/3 gene deletion, non-P. falciparum species, and low-density infections to false-negative RDT results under field conditions in Uganda. In view of these findings, the use of HRP2 RDTs should be reconsidered; possibly, switching to combination RDTs that target alternative antigens, particularly in affected areas, may be beneficial. Future evaluations should consider larger and more representative surveys covering other regions of Uganda.


Assuntos
Antígenos de Protozoários/isolamento & purificação , Malária Falciparum/diagnóstico , Plasmodium falciparum/isolamento & purificação , Proteínas de Protozoários/isolamento & purificação , Kit de Reagentes para Diagnóstico/estatística & dados numéricos , Antígenos de Protozoários/imunologia , Criança , Pré-Escolar , Estudos Transversais , DNA de Protozoário/isolamento & purificação , Teste em Amostras de Sangue Seco/instrumentação , Teste em Amostras de Sangue Seco/estatística & dados numéricos , Monitoramento Epidemiológico , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Masculino , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia , Reação em Cadeia da Polimerase/estatística & dados numéricos , Prevalência , Proteínas de Protozoários/imunologia , Uganda/epidemiologia
9.
PLoS One ; 15(12): e0242510, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382730

RESUMO

The specific immune response to the Anopheles salivary peptide could be a pertinent and complementary tool to assess the risk of malaria transmission and the effectiveness of vector control strategies. This study aimed to obtain first reliable data on the current state of the Anopheles gSG6-P1 biomarker for assess the level of exposure to Anopheles bites in high malaria endemic areas in Cameroon. Blood smears were collected from people living in the neighborhoods of Youpwe (suburban area, continental) and Manoka (rural area, Island), both areas in the coastal region of Cameroon. Malaria infection was determined using thick blood smear microscopy, whereas the level of specific IgG response to gSG-P1 peptide was assessed by enzyme-linked immunosorbent assay from the dried blood spots. Of 266 (153 from Youpwe, 113 from Manoka) malaria endemic residents (mean age: 22.8±19.8 years, age range: 6 months-94 years, male/female sex ratio: 1/1.2, with Manoka mean age: 23.71±20.53, male/female sex ratio:1/1.13 and Youpwe mean age: 22.12±19.22, male/female sex ratio 1/0.67) randomly included in the study, Plasmodium infection prevalence was significantly higher in Manoka than in Youpwe (64.6% vs 12,4%, p = 0.0001). The anti-gSG6-P1 IgG response showed a high inter-individual heterogeneity and was significantly higher among individuals from Manoka than those from Youpwe (p = 0.023). Malaria infected individuals presented a higher anti-gSG6-P1 IgG antibody response than non-infected (p = 0.0004). No significant difference in the level of specific IgG response to gSG-P1 was observed according to long lasting insecticidal nets use. Taken together, the data revealed that human IgG antibody response to Anopheles gSG-P1 salivary peptide could be also used to assess human exposure to malaria vectors in Central African region. This finding strengthens the relevance of this candidate biomarker to be used for measuring human exposure to malaria vectors worldwide.


Assuntos
Anopheles/parasitologia , Imunoglobulina G/sangue , Proteínas de Insetos/imunologia , Malária Falciparum/epidemiologia , Mosquitos Vetores/parasitologia , Plasmodium falciparum/imunologia , Proteínas e Peptídeos Salivares/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Camarões/epidemiologia , Criança , Pré-Escolar , Teste em Amostras de Sangue Seco , Doenças Endêmicas , Feminino , Humanos , Imunoglobulina G/biossíntese , Lactente , Proteínas de Insetos/sangue , Malária Falciparum/diagnóstico , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Prevalência , População Rural , Proteínas e Peptídeos Salivares/sangue , População Urbana
10.
Trends Parasitol ; 36(11): 880-883, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33036937

RESUMO

Malaria eradication is a global priority but requires innovative strategies. Humoral immune responses attack different parasite stages, and antibody-based therapy may prevent malaria infection or transmission. Here, we discuss targets of monoclonal antibodies in mosquito sexual stages of Plasmodium.


Assuntos
Anticorpos Monoclonais/imunologia , Culicidae/parasitologia , Estágios do Ciclo de Vida/imunologia , Malária/prevenção & controle , Malária/transmissão , Plasmodium falciparum/imunologia , Animais , Culicidae/imunologia , Erradicação de Doenças , Humanos , Malária/parasitologia
11.
Nat Commun ; 11(1): 5093, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037226

RESUMO

The mechanisms behind the ability of Plasmodium falciparum to evade host immune system are poorly understood and are a major roadblock in achieving malaria elimination. Here, we use integrative genomic profiling and a longitudinal pediatric cohort in Burkina Faso to demonstrate the role of post-transcriptional regulation in host immune response in malaria. We report a strong signature of miRNA expression differentiation associated with P. falciparum infection (127 out of 320 miRNAs, B-H FDR 5%) and parasitemia (72 miRNAs, B-H FDR 5%). Integrative miRNA-mRNA analysis implicates several infection-responsive miRNAs (e.g., miR-16-5p, miR-15a-5p and miR-181c-5p) promoting lymphocyte cell death. miRNA cis-eQTL analysis using whole-genome sequencing data identified 1,376 genetic variants associated with the expression of 34 miRNAs (B-H FDR 5%). We report a protective effect of rs114136945 minor allele on parasitemia mediated through miR-598-3p expression. These results highlight the impact of post-transcriptional regulation, immune cell death processes and host genetic regulatory control in malaria.


Assuntos
Evasão da Resposta Imune/genética , Malária Falciparum/genética , Malária Falciparum/imunologia , MicroRNAs/genética , Plasmodium falciparum/patogenicidade , Burkina Faso , Criança , Pré-Escolar , Regulação da Expressão Gênica , Genoma Humano , Humanos , Estudos Longitudinais , Parasitemia/genética , Parasitemia/imunologia , Plasmodium falciparum/imunologia , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/genética , Sequenciamento Completo do Genoma
12.
PLoS One ; 15(9): e0238749, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32886699

RESUMO

INTRODUCTION: False-negative malaria rapid diagnostic test (RDT) results amongst symptomatic malaria patients are detrimental as they could lead to ineffective malaria case management. This study determined the nationwide contribution of parasites with Pfhrp2 and Pfhrp 3 gene deletions to false negative malaria RDT results in Ghana. METHODS: This was a cross sectional study where whole blood (~2 ml) was collected from patients presenting with malaria symptoms at 100 health facilities in all the regions in Ghana from May to August 2018. An aliquot of the blood was used to prepare thin and thick blood smears, filter paper blood spots (DBS) and spot a PfHRP 2 RDT kit. The remaining blood was separated into plasma and blood cells and stored at -20°C. Plasmodium parasite density and species identity was estimated from the blood smears. Plasmodium falciparum specific 18S rRNA PCR, merozoite surface protein (msp 1) and glutamate rich protein (glurp) gene PCR were used to identify P. falciparum positive samples, which were subjected to Pfhrp 2/3 exon1-2 and exon2 genotyping. RESULTS: Of the 2,860 microscopically P. falciparum positive patients analyzed, 134 (4.69%) had false negative P. falciparum specific RDT results. Samples for PCR analysis was available for 127 of the false negative patients, and the analysis identified 116 (91.3%) as positive for P. falciparum. Only 58.1% (79/116) of the false negative RDT samples tested positive by msp 1 and glurp PCR. Genotyping of exon 1-2 and exon 2 of the Pfhrp 2 gene identified 12.9% (10/79) and 39.5% (31/79) of samples respectively to have deletions. Genotyping exon 1-2 and exon 2 of the Pfhrp 3 gene identified 15.2% (12/79) and 40.5% (32/79) of samples respectively to have deletions. Only 5% (4/79) of the false negative samples had deletions in both exon 1-2 and exon 2 of the Pfhrp 2 gene. Out of the 49 samples that tested positive for aldolase by luminex, 32.6% (16/49) and) had deletions in Pfhrp 2 exon 2 and 2% (1/49) had deletions in both exon 2 and exon 1-2 of the Pfhrp 2 gene. CONCLUSIONS: The low prevalence of false negative RDT test results provides assurance that PfHRP 2 based malaria RDT kits remain effective in diagnosing symptomatic malaria patients across all the Regions of Ghana. Although there was a low prevalence of parasites with deletions in exon 2 and exon 1-2 of the Pfhrp 2 gene the prevalence of parasites with deletions in Pfhrp 2 exon 2 was about a third of the false negative RDT results. The need to ensure rapid, accurate and reliable malaria diagnosis requires continuous surveillance of parasites with Pfhrp 2 gene deletions.


Assuntos
Antígenos de Protozoários/genética , Antígenos de Protozoários/metabolismo , Deleção de Genes , Malária Falciparum/diagnóstico , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Adulto , Antígenos de Protozoários/imunologia , Reações Falso-Negativas , Feminino , Técnicas de Genotipagem , Gana/epidemiologia , Humanos , Malária Falciparum/epidemiologia , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/imunologia , Plasmodium falciparum/fisiologia , Adulto Jovem
14.
Trends Parasitol ; 36(10): 802-804, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32800428

RESUMO

Among many Plasmodium proteins involved in the erythrocytic cycle, some exposed on the erythrocyte surface drive antigenic variability. Recently, Harrison et al. elucidated the structural basis by which RIFINs activate LILRB1 and suppress immune cell function. This breakthrough points to an additional strategy for survival in the human host.


Assuntos
Malária , Plasmodium , Antígenos CD , Comunicação Celular , Eritrócitos , Humanos , Receptor B1 de Leucócitos Semelhante a Imunoglobulina , Plasmodium falciparum/imunologia
15.
PLoS One ; 15(8): e0237786, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822376

RESUMO

Plasmodium falciparum malaria killed 451,000 people in 2017. Merozoites, the stage of the parasite that invades RBCs, are a logical target for vaccine development. Treatment with the protease inhibitor E64 followed by filtration through a 1.2 µm filter is being used to purify merozoites for immunologic assays. However, there have been no studies to determine the effect of these treatments on the susceptibility of merozoites to complement or antibodies. To address this gap, we purified merozoites with or without E64 followed by filtration through either a 1.2 or 2.7 µm filter, or no filtration. Merozoites were then incubated in either 10% fresh or heat-inactivated serum followed by surface staining and flow cytometry with monoclonal antibodies against the complement effector molecules C3b or C5b9. To determine the effect of anti-merozoite antibodies, we incubated merozoites with MAb5.2, a mouse monoclonal antibody that targets the merozoite surface protein 1. We used an amine-reactive fluorescent dye to measure membrane integrity. Treatment with E64 resulted in an insignificant increase in the proportion of merozoites that were C3b positive but in a significant increase in the proportion that were C5b9 positive. Filtration increased the proportion of merozoites that were either C3b or C5b9-positive. The combination of filtration and E64 treatment resulted in marked deposition of C3b and C5b9. MAb5.2 induced greater complement deposition than serum alone or an IgG2b isotype control. The combination of E64 treatment, filtration, and MAb5.2 resulted in very rapid and significant deposition of C5b9. Filtration through the 1.2 µm filter selected a population of merozoites with greater membrane integrity, but their integrity deteriorated rapidly upon exposure to serum. We conclude that E64 treatment and filtration increase the susceptibility of merozoites to complement and antibody. Filtered or E64-treated merozoites are not suitable for immunologic studies that address the efficacy of antibodies in vitro.


Assuntos
Merozoítos/efeitos dos fármacos , Merozoítos/isolamento & purificação , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/isolamento & purificação , Inibidores de Proteases/farmacologia , Animais , Anticorpos Antiprotozoários/imunologia , Ativação do Complemento/efeitos dos fármacos , Filtração , Citometria de Fluxo , Humanos , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Merozoítos/imunologia , Camundongos , Plasmodium falciparum/imunologia
16.
PLoS One ; 15(8): e0237671, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32797068

RESUMO

In high malaria transmission settings, the use of sulfadoxine-pyrimethamine-based intermittent preventive treatment during pregnancy (IPTp-SP) has resulted in decreased antibody (Ab) levels to VAR2CSA. However, information of Ab levels in areas of low or intermediate malaria transmission after long-term implementation of IPTp-SP is still lacking. The present study sought to evaluate antibody prevalence and levels in women at delivery in Etoudi, a peri-urban area in the capital of Yaoundé, Cameroon, that is a relatively low-malaria transmission area. Peripheral plasma samples from 130 pregnant women were collected at delivery and tested for IgG to the full-length recombinant VAR2CSA (FV2) and its most immunogenic subdomain, DBL5. The study was conducted between 2013 and 2015, approximately ten years after implementation of IPTp-SP in Cameroon. About 8.6% of the women attending the clinic had placental malaria (PM). One, two or 3 doses of SP did not impact significantly on either the percentage of women with Ab to FV2 and DBL5 or Ab levels in Ab-positive women compared to women not taking SP. The prevalence of Ab to FV2 and DBL5 was only 36.9% and 36.1%, respectively. Surprisingly, among women who had PM at delivery, only 61.5% and 57.7% had Ab to FV2 and DBL5, respectively, with only 52.9% and 47.1% in PM-positive paucigravidae and 77.7% of multigravidae having Ab to both antigens. These results suggest that long-term implementation of IPTp-SP in a low-malaria transmission area results in few women having Ab to VAR2CSA.


Assuntos
Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Antimaláricos/uso terapêutico , Malária Falciparum/prevenção & controle , Complicações Parasitárias na Gravidez/prevenção & controle , Pirimetamina/uso terapêutico , Sulfadoxina/uso terapêutico , Adulto , Anticorpos Antiprotozoários/sangue , Camarões/epidemiologia , Combinação de Medicamentos , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Malária/sangue , Malária/epidemiologia , Malária/imunologia , Malária/prevenção & controle , Malária Falciparum/sangue , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/imunologia , Gravidez , Complicações Parasitárias na Gravidez/sangue , Complicações Parasitárias na Gravidez/epidemiologia , Complicações Parasitárias na Gravidez/imunologia , Adulto Jovem
17.
BMC Infect Dis ; 20(1): 573, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758164

RESUMO

BACKGROUND: Malaria during pregnancy leads to serious adverse effects on mothers and the fetus. Approximately 25 million pregnant women in sub-Saharan Africa live at risk of malaria. This study would help to achieve Sustainable Development Goals (SDGs) by improving programs that deal with the prevention of malaria. Therefore, this study aimed to assess the prevalence and associated factors of malaria among pregnant women. METHODS: A community-based cross-sectional study was conducted from July to August 2018 in Sherkole district, West Ethiopia. A multi-stage sampling technique was used to select 504 pregnant women. The interviewer-administered semi-structured questionnaire was used for data collection. Malaria was also diagnosed using a rapid diagnostic test. The data was entered using EPI info version 7.2.2.2 and transferred to SPSS version 20 for analysis. Descriptive statistics were done using frequency and percentages. Both bivariable and multivariable logistic regression models were employed. Variables having p-value < 0.2 were included in the final multivariable model. Variables having p-values < 0.05 from the multivariable model were considered to be significantly associated with the dependent variable. The adjusted odds ratio with its 95% confidence interval (CI) was used as a measure of association. RESULTS: Of the total 498 pregnant women who participated in this study, 51(10.2, 95% CI: 7.72-13.24) were found to have malaria. Of these, 46 (90.2%) and 5 (9.8%) were caused by Plasmodium falciparum and Plasmodium vivax, respectively. Decreasing Age (Adjusted Odds Ratio (AOR) 0.78; 95% CI 0.67-0.911), not using insecticide-treated bed net (ITN) (AOR 12.5; 95% CI 4.86-32.21), lack of consultation and health education about malaria prevention (AOR 7.18; 95% CI 2.74-18.81), being on second-trimester pregnancy (AOR 7.58; 95% CI 2.84-20.2), gravidae II (AOR 5.99; 95% CI 1.68-21.44) were found to be significantly associated with malaria during pregnancy. CONCLUSION: Malaria is still a public health problem among pregnant women in the Sherkole district. Age, ITN use, gravidity, gestational age, and health education had a significant association with malaria. Screening pregnant women for asymptomatic malaria infection and educating and consulting on the appropriate malaria preventive methods shall be provided.


Assuntos
Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Plasmodium falciparum/imunologia , Plasmodium vivax/imunologia , Complicações Parasitárias na Gravidez/epidemiologia , Adolescente , Adulto , Antígenos de Protozoários/sangue , Infecções Assintomáticas , Estudos Transversais , Testes Diagnósticos de Rotina/métodos , Etiópia/epidemiologia , Feminino , Seguimentos , Humanos , Mosquiteiros Tratados com Inseticida , Modelos Logísticos , Malária Falciparum/prevenção & controle , Malária Vivax/prevenção & controle , Razão de Chances , Gravidez , Complicações Parasitárias na Gravidez/prevenção & controle , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
18.
J Vis Exp ; (162)2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32831311

RESUMO

The protocol describes how to set up and run a flow cytometry-based phagocytosis assay of Plasmodium falciparum-infected erythrocytes (IEs) opsonized by naturally acquired IgG antibodies specific for VAR2CSA. VAR2CSA is the parasite antigen that mediates the selective sequestration of IEs in the placenta that can cause a severe form of malaria in pregnant women, called placental malaria (PM). Protection from PM is mediated by VAR2CSA-specific antibodies that are believed to function by inhibiting placental sequestration and/or by opsonizing IEs for phagocytosis. The assay employs late-stage-synchronized IEs that have been selected in vitro to express VAR2CSA, plasma/serum-antibodies from women with naturally acquired PM-specific immunity, and the phagocytic cell line THP-1. However, the protocol can easily be modified to assay the functionality of antibodies to any parasite antigen present on the IE surface, whether induced by natural exposure or by vaccination. The assay offers simple and high-throughput evaluation, with good reproducibility, of an important functional aspect of antibody-mediated immunity in malaria. It is, therefore, useful when evaluating clinical immunity to P. falciparum malaria, a major cause of morbidity and mortality in the tropics, particularly in sub-Saharan Africa.


Assuntos
Anticorpos Antiprotozoários/análise , Bioensaio/métodos , Citometria de Fluxo/métodos , Parasitos/imunologia , Fagocitose , Plasmodium falciparum/imunologia , Animais , Antígenos de Protozoários/imunologia , Eritrócitos/parasitologia , Feminino , Humanos , Malária Falciparum/sangue , Malária Falciparum/parasitologia , Proteínas Opsonizantes/metabolismo , Gravidez , Receptores Fc/metabolismo , Reprodutibilidade dos Testes , Células THP-1
19.
Am J Trop Med Hyg ; 103(5): 1902-1909, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32840197

RESUMO

In malaria-endemic countries, rapid diagnostic tests (RDTs) targeting Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and lactate dehydrogenase (PfLDH) have been widely used. However, little is known regarding the diagnostic performances of these RDTs in the Assosa zone of northwest Ethiopia. The objective of this study was to determine the diagnostic performances of PfHRP2 and PfLDH RDTs using microscopy and quantitative PCR (qPCR) as a reference test. A health facility-based cross-sectional study design was conducted from malaria-suspected study participants at selected health centers from November to December 2018. Finger-prick blood samples were collected for microscopy, RDTs, and qPCR method. The prevalence of P. falciparum was 26.4%, 30.3%, and 24.1% as determined by microscopy, PfHRP2 RDT, and PfLDH RDT, respectively. Compared with microscopy, the sensitivity and specificity of the PfHRP2 RDT were 96% and 93%, respectively, and those of the PfLDH RDT were 89% and 99%, respectively. Compared with qPCR, the specificity of the PfHRP2 RDT (93%) and PfLDH RDT (98%) was high, but the sensitivity of the PfHRP2 RDT (77%) and PfLDH RDT (70%) was relatively low. These malaria RDTs and reference microscopy methods showed reasonable agreement with a kappa value above 0.85 and provided accurate diagnosis of P. falciparum malaria. Thus, the current malaria RDT in the Ministry of Health program can be used in the Assosa zone of Ethiopia. However, continuous monitoring of the performance of PfHRP2 RDT is important to support control and elimination of malaria in Ethiopia.


Assuntos
Antígenos de Protozoários/imunologia , Testes Diagnósticos de Rotina/métodos , L-Lactato Desidrogenase/imunologia , Malária Falciparum/diagnóstico , Plasmodium falciparum/isolamento & purificação , Proteínas de Protozoários/imunologia , Adolescente , Adulto , Antígenos de Protozoários/genética , Criança , Pré-Escolar , Estudos Transversais , Demografia , Etiópia , Feminino , Geografia , Humanos , L-Lactato Desidrogenase/genética , Malária Falciparum/parasitologia , Masculino , Microscopia , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia , Reação em Cadeia da Polimerase , Proteínas de Protozoários/genética , Sensibilidade e Especificidade , Adulto Jovem
20.
PLoS One ; 15(7): e0236375, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726331

RESUMO

BACKGROUND: Malaria in pregnancy causes maternal, fetal and neonatal morbidity and mortality, and maternal innate immune responses are implicated in pathogenesis of these complications. The effects of malaria exposure and obstetric and demographic factors on the early maternal immune response are poorly understood. METHODS: Peripheral blood mononuclear cell responses to Plasmodium falciparum-infected erythrocytes and phytohemagglutinin were compared between pregnant women from Papua New Guinea (malaria-exposed) with and without current malaria infection and from Australia (unexposed). Elicited levels of inflammatory cytokines at 48 h and 24 h (interferon γ, IFN-γ only) and the cellular sources of IFN-γ were analysed. RESULTS: Among Papua New Guinean women, microscopic malaria at enrolment did not alter peripheral blood mononuclear cell responses. Compared to samples from Australia, cells from Papua New Guinean women secreted more inflammatory cytokines tumor necrosis factor-α, interleukin 1ß, interleukin 6 and IFN-γ; p<0.001 for all assays, and more natural killer cells produced IFN-γ in response to infected erythrocytes and phytohemagglutinin. In both populations, cytokine responses were not affected by gravidity, except that in the Papua New Guinean cohort multigravid women had higher IFN-γ secretion at 24 h (p = 0.029) and an increased proportion of IFN-γ+ Vδ2 γδ T cells (p = 0.003). Cytokine levels elicited by a pregnancy malaria-specific CSA binding parasite line, CS2, were broadly similar to those elicited by CD36-binding line P6A1. CONCLUSIONS: Geographic location and, to some extent, gravidity influence maternal innate immunity to malaria.


Assuntos
Imunidade Inata/genética , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Complicações Parasitárias na Gravidez/imunologia , Adolescente , Adulto , Austrália/epidemiologia , Antígenos CD36/genética , Eritrócitos/imunologia , Eritrócitos/parasitologia , Eritrócitos/patologia , Feminino , Número de Gestações/imunologia , Humanos , Interferon gama/genética , Interferon gama/imunologia , Interleucina-6/genética , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/parasitologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/parasitologia , Leucócitos Mononucleares/patologia , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Pessoa de Meia-Idade , Papua Nova Guiné/epidemiologia , Plasmodium falciparum/patogenicidade , Gravidez , Complicações Parasitárias na Gravidez/parasitologia , Complicações Parasitárias na Gravidez/patologia , Linfócitos T/imunologia , Linfócitos T/parasitologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...