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1.
Front Immunol ; 15: 1392043, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962015

RESUMO

In the Americas, P. vivax is the predominant causative species of malaria, a debilitating and economically significant disease. Due to the complexity of the malaria parasite life cycle, a vaccine formulation with multiple antigens expressed in various parasite stages may represent an effective approach. Based on this, we previously designed and constructed a chimeric recombinant protein, PvRMC-1, composed by PvCyRPA, PvCelTOS, and Pvs25 epitopes. This chimeric protein was strongly recognized by naturally acquired antibodies from exposed population in the Brazilian Amazon. However, there was no investigation about the induced immune response of PvRMC-1. Therefore, in this work, we evaluated the immunogenicity of this chimeric antigen formulated in three distinct adjuvants: Stimune, AddaVax or Aluminum hydroxide (Al(OH)3) in BALB/c mice. Our results suggested that the chimeric protein PvRMC-1 were capable to generate humoral and cellular responses across all three formulations. Antibodies recognized full-length PvRMC-1 and linear B-cell epitopes from PvCyRPA, PvCelTOS, and Pvs25 individually. Moreover, mice's splenocytes were activated, producing IFN-γ in response to PvCelTOS and PvCyRPA peptide epitopes, affirming T-cell epitopes in the antigen. While aluminum hydroxide showed notable cellular response, Stimune and Addavax induced a more comprehensive immune response, encompassing both cellular and humoral components. Thus, our findings indicate that PvRMC-1 would be a promising multistage vaccine candidate that could advance to further preclinical studies.


Assuntos
Anticorpos Antiprotozoários , Antígenos de Protozoários , Vacinas Antimaláricas , Malária Vivax , Camundongos Endogâmicos BALB C , Plasmodium vivax , Proteínas de Protozoários , Animais , Plasmodium vivax/imunologia , Plasmodium vivax/genética , Camundongos , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/genética , Malária Vivax/imunologia , Malária Vivax/prevenção & controle , Anticorpos Antiprotozoários/imunologia , Vacinas Antimaláricas/imunologia , Feminino , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/genética , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Modelos Animais de Doenças , Adjuvantes Imunológicos , Imunogenicidade da Vacina , Antígenos de Superfície
2.
Artigo em Inglês | MEDLINE | ID: mdl-38928926

RESUMO

Multidrug- and artemisinin-resistant (ART-R) Plasmodium falciparum (Pf) parasites represent a challenge for malaria elimination worldwide. Molecular monitoring in the Kelch domain region (pfk13) gene allows tracking mutations in parasite resistance to artemisinin. The increase in illegal miners in the Roraima Yanomami indigenous land (YIL) could favor ART-R parasites. Thus, this study aimed to investigate ART-R in patients from illegal gold mining areas in the YIL of Roraima, Brazil. A questionnaire was conducted, and blood was collected from 48 patients diagnosed with P. falciparum or mixed malaria (Pf + P. vivax). The DNA was extracted and the pfk13 gene was amplified by PCR. The amplicons were subjected to DNA-Sanger-sequencing and the entire amplified fragment was analyzed. Among the patients, 96% (46) were from illegal mining areas of the YIL. All parasite samples carried the wild-type genotypes/ART-sensitive phenotypes. These data reinforce the continued use of artemisinin-based combination therapies (ACTs) in Roraima, as well as the maintenance of systematic monitoring for early detection of parasite populations resistant to ART, mainly in regions with an intense flow of individuals from mining areas, such as the YIL. This is especially true when the achievement of falciparum malaria elimination in Brazil is planned and expected by 2030.


Assuntos
Antimaláricos , Artemisininas , Resistência a Medicamentos , Malária Falciparum , Mineração , Plasmodium falciparum , Artemisininas/uso terapêutico , Artemisininas/farmacologia , Brasil/epidemiologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Humanos , Antimaláricos/uso terapêutico , Antimaláricos/farmacologia , Resistência a Medicamentos/genética , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Genótipo
3.
Malariaworld J ; 15: 8, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737169

RESUMO

Plasmodium vivax causes the vast majority of malaria cases in Brazil. The lifecycle of this parasite includes a latent stage in the liver, the hypnozoite. Reactivation of hypnozoites induces repeated relapses. We report a case of two relapses of vivax malaria in a teenage girl after conventional treatment with chloroquine and primaquine. Chloroquine prophylactic treatment for three months was prescribed with a favourable outcome of the case.

4.
Mol Biol Rep ; 51(1): 594, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683374

RESUMO

BACKGROUND: Metacaspases comprise a family of cysteine proteases implicated in both cell death and cell differentiation of protists that has been considered a potential drug target for protozoan parasites. However, the biology of metacaspases in Plasmodium vivax - the second most prevalent and most widespread human malaria parasite worldwide, whose occurrence of chemoresistance has been reported in many endemic countries, remains largely unexplored. Therefore, the present study aimed to address, for the first time, the expression pattern of metacaspases in P. vivax parasites. METHODS AND RESULTS: P. vivax blood-stage parasites were obtained from malaria patients in the Brazilian Amazon and the expression of the three putative P. vivax metacaspases (PvMCA1-3) was detected in all isolates by quantitative PCR assay. Of note, the expression levels of each PvMCA varied noticeably across isolates, which presented different frequencies of parasite forms, supporting that PvMCAs may be expressed in a stage-specific manner as previously shown in P. falciparum. CONCLUSION: The detection of metacaspases in P. vivax blood-stage parasites reported herein, allows the inclusion of these proteases as a potential candidate drug target for vivax malaria, while further investigations are still required to evaluate the activity, role and essentiality of metacaspases in P. vivax biology.


Assuntos
Malária Vivax , Plasmodium vivax , Proteínas de Protozoários , Plasmodium vivax/genética , Plasmodium vivax/isolamento & purificação , Brasil , Humanos , Malária Vivax/parasitologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Caspases/genética , Caspases/metabolismo , Expressão Gênica/genética
5.
Biomedicines ; 12(1)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38255246

RESUMO

(1) Background: Malaria remains a significant global public health issue. Since parasites quickly became resistant to most of the available antimalarial drugs, treatment effectiveness must be constantly monitored. In Brazil, up to 10% of cases of vivax malaria resistant to chloroquine (CQ) have been registered. Unlike P. falciparum, there are no definitive molecular markers for the chemoresistance of P. vivax to CQ. This work aimed to investigate whether polymorphisms in the pvcrt-o and pvmdr1 genes could be used as markers for assessing its resistance to CQ. (2) Methods: A total of 130 samples from P. vivax malaria cases with no clinical and/or parasitological evidence of CQ resistance were studied through polymerase chain reaction for gene amplification followed by target DNA sequencing. (3) Results: In the pvcrt-o exons, the K10 insert was present in 14% of the isolates. Regarding pvmdr1, T958M and F1076L haplotypes showed frequencies of 95% and 3%, respectively, while the SNP Y976F was not detected. (4) Conclusions: Since K10-pvcrt-o and F1076L/T958M-pvmdr1 polymorphisms were detected in samples from patients who responded well to CQ treatment, it can be concluded that mutations in these genes do not seem to have a potential for association with the phenotype of CQ resistance.

6.
One Health ; 17: 100624, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38024260

RESUMO

Notwithstanding the understandable rationale of the logical, expected and natural evolution of human behaviour towards an anthropocentric view of its relationship with other animals and the environment, a shift from this predatory "Ego-centric" behaviour towards an "Eco" conduct, with regard to their view of the world and of the global health, has become mandatory, contributing to the development of the "One Health" and of "One Health Systems" concepts. We contend for the usefulness of a building-blocks approach to facilitate an understanding of the development of One Health Systems. We assert that a building-blocks approach to One Health Systems with strong similarity to WHO's building-blocks for human health systems would help to strengthen the case for robust,resilient and anti-fragile One Health systems.

7.
Front Cell Infect Microbiol ; 13: 1169552, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37829607

RESUMO

Introduction: Zoonotic transmission is a challenge for the control and elimination of malaria. It has been recorded in the Atlantic Forest, outside the Amazon which is the endemic region in Brazil. However, only very few studies have assessed the antibody response, especially of IgM antibodies, in Neotropical primates (NP). Therefore, in order to contribute to a better understanding of the immune response in different hosts and facilitate the identification of potential reservoirs, in this study, naturally acquired IgM antibody responses against Plasmodium antigens were evaluated, for the first time, in NP from the Atlantic Forest. Methods: The study was carried out using 154 NP samples from three different areas of the Atlantic Forest. IgM antibodies against peptides of the circumsporozoite protein (CSP) from different Plasmodium species and different erythrocytic stage antigens were detected by ELISA. Results: Fifty-nine percent of NP had IgM antibodies against at least one CSP peptide and 87% against at least one Plasmodium vivax erythrocytic stage antigen. Levels of antibodies against PvAMA-1 were the highest compared to the other antigens. All families of NP showed IgM antibodies against CSP peptides, and, most strikingly, against erythrocytic stage antigens. Generalized linear models demonstrated that IgM positivity against PvCSP and PvAMA-1 was associated with PCR-detectable blood-stage malaria infection and the host being free-living. Interestingly, animals with IgM against both PvCSP and PvAMA-1 were 4.7 times more likely to be PCR positive than animals that did not have IgM for these two antigens simultaneously. Discussion: IgM antibodies against different Plasmodium spp. antigens are present in NP from the Atlantic Forest. High seroprevalence and antibody levels against blood-stage antigens were observed, which had a significant association with molecular evidence of infection. IgM antibodies against CSP and AMA-1 may be used as a potential marker for the identification of NP infected with Plasmodium, which are reservoirs of malaria in the Brazilian Atlantic Forest.


Assuntos
Malária , Plasmodium , Animais , Brasil/epidemiologia , Formação de Anticorpos , Proteínas de Protozoários , Imunoglobulina M , Estudos Soroepidemiológicos , Antígenos de Protozoários , Malária/veterinária , Primatas , Florestas , Anticorpos Antiprotozoários , Peptídeos , Plasmodium vivax
8.
Malar J ; 22(1): 303, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37814260

RESUMO

BACKGROUND: Malaria is endemic and represents an important public health issue in Brazil. Knowledge of risk factors for disease progression represents an important step in preventing and controlling malaria-related complications. Reports of severe forms of Plasmodium vivax malaria are now becoming a common place, but respiratory complications are described in less than 3% of global literature on severe vivax malaria. CASE PRESENTATION: A severe respiratory case of imported vivax malaria in a previously healthy 40-year-old woman has been reported. The patient died after the fifth day of treatment with chloroquine and primaquine due to acute respiratory distress syndrome. CONCLUSIONS: Respiratory symptoms started 48 h after the initiation of anti-malarial drugs, raising the hypothesis that the drugs may have been involved in the genesis of the complication. The concept that vivax malaria is a benign disease that can sometimes result in the development of serious complications must be disseminated. This report highlights, once more, the crucial importance of malaria early diagnosis, a true challenge in non-endemic areas, where health personnel are not familiar with the disease and do not consider its diagnosis promptly.


Assuntos
Antimaláricos , Malária Vivax , Malária , Adulto , Feminino , Humanos , Antimaláricos/efeitos adversos , Malária/epidemiologia , Malária Vivax/complicações , Malária Vivax/tratamento farmacológico , Malária Vivax/diagnóstico , Plasmodium vivax , Primaquina/efeitos adversos
9.
Int J Mol Sci ; 24(14)2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37511092

RESUMO

Newly emerging data suggest that several neutrophil defense mechanisms may play a role in both aggravating and protecting against malaria. These exciting findings suggest that the balance of these cells in the host body may have an impact on the pathogenesis of malaria. To fully understand the role of neutrophils in severe forms of malaria, such as cerebral malaria (CM), it is critical to gain a comprehensive understanding of their behavior and functions. This study investigated the dynamics of neutrophil and T cell responses in C57BL/6 and BALB/c mice infected with Plasmodium berghei ANKA, murine models of experimental cerebral malaria (ECM) and non-cerebral experimental malaria, respectively. The results demonstrated an increase in neutrophil percentage and neutrophil-T cell ratios in the spleen and blood before the development of clinical signs of ECM, which is a phenomenon not observed in the non-susceptible model of cerebral malaria. Furthermore, despite the development of distinct forms of malaria in the two strains of infected animals, parasitemia levels showed equivalent increases throughout the infection period evaluated. These findings suggest that the neutrophil percentage and neutrophil-T cell ratios may be valuable predictive tools for assessing the dynamics and composition of immune responses involved in the determinism of ECM development, thus contributing to the advancing of our understanding of its pathogenesis.


Assuntos
Malária Cerebral , Animais , Camundongos , Neutrófilos/patologia , Camundongos Endogâmicos C57BL , Plasmodium berghei , Linfócitos T CD8-Positivos , Modelos Animais de Doenças
10.
Int J Biol Sci ; 19(11): 3383-3394, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37496995

RESUMO

The immune and nervous systems can be thought of as cognitive and plastic systems, since they are both involved in cognition/recognition processes and can be architecturally and functionally modified by experience, and such changes can influence each other's functioning. The immune system can affect nervous system function depending on the nature of the immune stimuli and the pro/anti-inflammatory responses they generate. Here we consider interactions between the immune and nervous systems in homeostasis and disease, including the beneficial and deleterious effects of immune stimuli on brain function and the impact of severe and non-severe malaria parasite infections on neurocognitive and behavioral parameters in human and experimental murine malaria. We also discuss the effect of immunization on the reversal of cognitive deficits associated with experimental non-severe malaria in a model susceptible to the development of the cerebral form of the illness. Finally, we consider the possibility of using human vaccines, largely exploited as immune-prophylactics for infectious diseases, as therapeutic tools to prevent or mitigate the expression of cognitive deficits in infectious and chronic degenerative diseases.


Assuntos
Transtornos Cognitivos , Malária , Humanos , Animais , Camundongos , Malária/parasitologia , Encéfalo , Transtornos Cognitivos/parasitologia , Cognição , Homeostase
11.
Int J Mol Sci ; 24(14)2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37511330

RESUMO

The PvCelTOS, PvCyRPA, and Pvs25 proteins play important roles during the three stages of the P. vivax lifecycle. In this study, we designed and expressed a P. vivax recombinant modular chimeric protein (PvRMC-1) composed of the main antigenic regions of these vaccine candidates. After structure modelling by prediction, the chimeric protein was expressed, and the antigenicity was assessed by IgM and IgG (total and subclass) ELISA in 301 naturally exposed individuals from the Brazilian Amazon. The recombinant protein was recognized by IgG (54%) and IgM (40%) antibodies in the studied individuals, confirming the natural immunogenicity of the epitopes that composed PvRMC-1 as its maintenance in the chimeric structure. Among responders, a predominant cytophilic response mediated by IgG1 (70%) and IgG3 (69%) was observed. IgM levels were inversely correlated with age and time of residence in endemic areas (p < 0.01). By contrast, the IgG and IgM reactivity indexes were positively correlated with each other, and both were inversely correlated with the time of the last malaria episode. Conclusions: The study demonstrates that PvRMC-1 was successfully expressed and targeted by natural antibodies, providing important insights into the construction of a multistage chimeric recombinant protein and the use of naturally acquired antibodies to validate the construction.


Assuntos
Malária Vivax , Plasmodium vivax , Humanos , Plasmodium vivax/genética , Imunidade Humoral , Proteínas de Protozoários/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes de Fusão/genética , Imunoglobulina G , Imunoglobulina M/genética , Antígenos de Protozoários/genética
12.
Malar J ; 22(1): 170, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37268984

RESUMO

BACKGROUND: Plasmodium species of non-human primates (NHP) are of great interest because they can naturally infect humans. Plasmodium simium, a parasite restricted to the Brazilian Atlantic Forest, was recently shown to cause a zoonotic outbreak in the state of Rio de Janeiro. The potential of NHP to act as reservoirs of Plasmodium infection presents a challenge for malaria elimination, as NHP will contribute to the persistence of the parasite. The aim of the current study was to identify and quantify gametocytes in NHP naturally-infected by P. simium. METHODS: Whole blood samples from 35 NHP were used in quantitative reverse transcription PCR (RT-qPCR) assays targeting 18S rRNA, Pss25 and Pss48/45 malaria parasite transcripts. Absolute quantification was performed in positive samples for 18S rRNA and Pss25 targets. Linear regression was used to compare the quantification cycle (Cq) and the Spearman's rank correlation coefficient was used to assess the correlation between the copy numbers of 18S rRNA and Pss25 transcripts. The number of gametocytes/µL was calculated by applying a conversion factor of 4.17 Pss25 transcript copies per gametocyte. RESULTS: Overall, 87.5% of the 26 samples, previously diagnosed as P. simium, were positive for 18S rRNA transcript amplification, of which 13 samples (62%) were positive for Pss25 transcript amplification and 7 samples (54%) were also positive for Pss48/45 transcript. A strong positive correlation was identified between the Cq of the 18S rRNA and Pss25 and between the Pss25 and Pss48/45 transcripts. The 18S rRNA and Pss25 transcripts had an average of 1665.88 and 3.07 copies/µL, respectively. A positive correlation was observed between the copy number of Pss25 and 18S rRNA transcripts. Almost all gametocyte carriers exhibited low numbers of gametocytes (< 1/µL), with only one howler monkey having 5.8 gametocytes/µL. CONCLUSIONS: For the first time, a molecular detection of P. simium gametocytes in the blood of naturally-infected brown howler monkeys (Alouatta guariba clamitans) was reported here, providing evidence that they are likely to be infectious and transmit P. simium infection, and, therefore, may act as a reservoir of malaria infection for humans in the Brazilian Atlantic Forest.


Assuntos
Malária , Plasmodium , Animais , Humanos , RNA Ribossômico 18S/genética , Brasil/epidemiologia , Plasmodium/genética , Malária/epidemiologia , Malária/veterinária , Malária/parasitologia , Primatas/genética , Florestas , Plasmodium falciparum/genética
13.
Microorganisms ; 11(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37374974

RESUMO

The concept of molecular mimicry describes situations in which antigen sharing between parasites and hosts could benefit pathogen evasion from host immune responses. However, antigen sharing can generate host responses to parasite-derived self-like peptides, triggering autoimmunity. Since its conception, molecular mimicry and the consequent potential cross-reactivity following infections have been repeatedly described in humans, raising increasing interest among immunologists. Here, we reviewed this concept focusing on the challenge of maintaining host immune tolerance to self-components in parasitic diseases. We focused on the studies that used genomics and bioinformatics to estimate the extent of antigen sharing between proteomes of different organisms. In addition, we comparatively analyzed human and murine proteomes for peptide sharing with proteomes of pathogenic and non-pathogenic organisms. We conclude that, although the amount of antigenic sharing between hosts and both pathogenic and non-pathogenic parasites and bacteria is massive, the degree of this antigen sharing is not related to pathogenicity or virulence. In addition, because the development of autoimmunity in response to infections by microorganisms endowed with cross-reacting antigens is rare, we conclude that molecular mimicry by itself is not a sufficient factor to disrupt intact self-tolerance mechanisms.

14.
Pathogens ; 12(5)2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37242401

RESUMO

(1) Background: Malaria is a public health problem worldwide. Despite global efforts to control it, antimalarial drug resistance remains a great challenge. In 2009, our team identified, for the first time in Brazil, chloroquine (CQ)-susceptible Plasmodium falciparum parasites in isolates from the Brazilian Amazon. The present study extends those observations to include survey samples from 2010 to 2018 from the Amazonas and Acre states for the purpose of tracking pfcrt molecular changes in P. falciparum parasites. (2) Objective: to investigate SNPs in the P. falciparum gene associated with chemoresistance to CQ (pfcrt). (3) Methods: Sixty-six P. falciparum samples from the Amazonas and Acre states were collected from 2010 to 2018 in patients diagnosed at the Reference Research Center for Treatment and Diagnosis of Malaria (CPD-Mal/Fiocruz), FMT-HVD and Acre Health Units. These samples were subjected to PCR and DNA Sanger sequencing to identify mutations in pfcrt (C72S, M74I, N75E, and K76T). (4) Results: Of the 66 P. falciparum samples genotyped for pfcrt, 94% carried CQ-resistant genotypes and only 4 showed a CQ pfcrt sensitive-wild type genotype, i.e., 1 from Barcelos and 3 from Manaus. (5) Conclusion: CQ-resistant P. falciparum populations are fixed, and thus, CQ cannot be reintroduced in malaria falciparum therapy.

15.
Mem Inst Oswaldo Cruz ; 118: e230023, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37162063

RESUMO

Innate immunity refers to the mechanisms responsible for the first line of defense against pathogens, cancer cells and toxins. The innate immune system is also responsible for the initial activation of the body's specific immune response (adaptive immunity). Innate immunity was studied and further developed in parallel with adaptive immunity beginning in the first half of the 19th century and has been gaining increasing importance to our understanding of health and disease. In the present overview, we describe the main findings and ideas that contributed to the development of innate immunity as a continually expanding branch of modern immunology. We start with the toxicological studies by Von Haller and Magendie, in the late 18th and early 19th centuries, and continue with the discoveries in invertebrate immunity that supported the discovery and characterization of lipopolysaccharide (LPS) and pattern recognition receptors that led to the development of the pattern recognition and danger theory.


Assuntos
Imunidade Inata
17.
Vaccines (Basel) ; 11(2)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36851323

RESUMO

The GMZ2.6c malaria vaccine candidate is a multi-stage P. falciparum chimeric protein that contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, an asexual-stage vaccine construction consisting of the N-terminal region of the glutamate-rich protein (GLURP) and the C-terminal region of the merozoite surface protein-3 (MSP-3). Previous studies showed that GMZ2.6c is widely recognized by antibodies from Brazilian exposed individuals and that its components are immunogenic in natural infection by P. falciparum. In addition, anti-GMZ2.6c antibodies increase with exposure to infection and may contribute to parasite immunity. Therefore, identifying epitopes of proteins recognized by antibodies may be an important tool for understanding protective immunity. Herein, we identify and validate the B-cell epitopes of GMZ2.6c as immunogenic and immunodominant in individuals exposed to malaria living in endemic areas of the Brazilian Amazon. Specific IgG antibodies and subclasses against MSP-3, GLURP, and Pfs48/45 epitopes were detected by ELISA using synthetic peptides corresponding to B-cell epitopes previously described for MSP-3 and GLURP or identified by BepiPred for Pfs48/45. The results showed that the immunodominant epitopes were P11 from GLURP and MSP-3c and DG210 from MSP-3. The IgG1 and IgG3 subclasses were preferentially induced against these epitopes, supporting previous studies that these proteins are targets for cytophilic antibodies, important for the acquisition of protective immunity. Most individuals presented detectable IgG antibodies against Pfs48/45a and/or Pfs48/45b, validating the prediction of linear B-cell epitopes. The higher frequency and antibody levels against different epitopes from GLURP, MSP-3, and Pfs48/45 provide additional information that may suggest the relevance of GMZ2.6c as a multi-stage malaria vaccine candidate.

18.
Mem Inst Oswaldo Cruz ; 117: e220184, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36700582

RESUMO

BACKGROUND: Cerebral malaria is a lethal complication of Plasmodium falciparum infections in need of better therapies. Previous work in murine experimental cerebral malaria (ECM) indicated that the combination of artemether plus intraperitoneal whole blood improved vascular integrity and increased survival compared to artemether alone. However, the effects of blood or plasma transfusion administered via the intravenous route have not previously been evaluated in ECM. OBJECTIVES: To evaluate the effects of intravenous whole blood compared to intravenous plasma on hematological parameters, vascular integrity, and survival in artemether-treated ECM. METHODS: Mice with late-stage ECM received artemether alone or in combination with whole blood or plasma administered via the jugular vein. The outcome measures were hematocrit and platelets; plasma angiopoietin 1, angiopoietin 2, and haptoglobin; blood-brain barrier permeability; and survival. FINDINGS: Survival increased from 54% with artemether alone to 90% with the combination of artemether and intravenous whole blood. Intravenous plasma lowered survival to 18%. Intravenous transfusion provided fast and pronounced recoveries of hematocrit, platelets, angiopoietins levels and blood brain barrier integrity. MAIN CONCLUSIONS: The outcome of artemether-treated ECM was improved by intravenous whole blood but worsened by intravenous plasma. Compared to prior studies of transfusion via the intraperitoneal route, intravenous administration was more efficacious.


Assuntos
Antimaláricos , Artemisininas , Malária Cerebral , Malária Falciparum , Animais , Camundongos , Malária Cerebral/complicações , Malária Cerebral/tratamento farmacológico , Antimaláricos/uso terapêutico , Transfusão de Componentes Sanguíneos , Plasma , Artemeter/uso terapêutico , Malária Falciparum/tratamento farmacológico , Administração Intravenosa
19.
Brain Behav Immun ; 109: 102-104, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36657622

RESUMO

Malaria, an ancient infectious parasitic disease, is caused by protozoa of the genus Plasmodium, whose erythrocytic cycle is accompanied by fever, headache, sweating and chills and a systemic inflammation that can progress to severe forms of disease, including cerebral malaria. Approximately 25% of survivors of this syndrome develop sequelae that may include neurological, neurocognitive, behavioral alterations and poor school performance. Furthermore, some outcomes have also been recorded following episodes of non-severe malaria, which correspond to the most common clinical form of the disease worldwide. There is a body of evidence that neuroinflammation, due to systemic inflammation, plays an important role in the neuropathogenesis of malaria culminating in these cognitive dysfunctions. Preclinical studies suggest that vaccination with type 2 immune response elicitors, such as the tetanus-diphtheria (Td) vaccine, may exert a beneficial immunomodulatory effect by alleviating neuroinflammation. In this viewpoint article, vaccination is proposed as a therapy approach to revert or mitigate neurocognitive deficits associated with malaria.


Assuntos
Malária Cerebral , Doenças Neuroinflamatórias , Humanos , Malária Cerebral/complicações , Vacina contra Difteria e Tétano , Vacinação , Inflamação , Imunidade
20.
Mem. Inst. Oswaldo Cruz ; 118: e230023, 2023. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1440669

RESUMO

Innate immunity refers to the mechanisms responsible for the first line of defense against pathogens, cancer cells and toxins. The innate immune system is also responsible for the initial activation of the body's specific immune response (adaptive immunity). Innate immunity was studied and further developed in parallel with adaptive immunity beginning in the first half of the 19th century and has been gaining increasing importance to our understanding of health and disease. In the present overview, we describe the main findings and ideas that contributed to the development of innate immunity as a continually expanding branch of modern immunology. We start with the toxicological studies by Von Haller and Magendie, in the late 18th and early 19th centuries, and continue with the discoveries in invertebrate immunity that supported the discovery and characterization of lipopolysaccharide (LPS) and pattern recognition receptors that led to the development of the pattern recognition and danger theory.

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