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.
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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 SuperfícieRESUMO
Background: The integration of diagnostic methods holds promise for advancing the surveillance of malaria transmission in both endemic and non-endemic regions. Serological assays emerge as valuable tools to identify and delimit malaria transmission, serving as a complementary method to rapid diagnostic tests (RDT) and thick smear microscopy. Here, we evaluate the potential of antibodies directed against peptides encompassing the entire amino acid sequence of the PvMSP-1 Sal-I strain as viable serological biomarkers for P. vivax exposure. Methods: We screened peptides encompassing the complete amino acid sequence of the Plasmodium vivax Merozoite Surface Protein 1 (PvMSP-1) Sal-I strain as potential biomarkers for P. vivax exposure. Here, immunodominant peptides specifically recognized by antibodies from individuals infected with P. vivax were identified using the SPOT-synthesis technique followed by immunoblotting. Two 15-mer peptides were selected based on their higher and specific reactivity in immunoblotting assays. Subsequently, peptides p70 and p314 were synthesized in soluble form using SPPS (Solid Phase Peptide Synthesis) and tested by ELISA (IgG, and subclasses). Results: This study unveils the presence of IgG antibodies against the peptide p314 in most P. vivax-infected individuals from the Brazilian Amazon region. In silico B-cell epitope prediction further supports the utilization of p314 as a potential biomarker for evaluating malaria transmission, strengthened by its amino acid sequence being part of a conserved block of PvMSP-1. Indeed, compared to patients infected with P. falciparum and uninfected individuals never exposed to malaria, P. vivax-infected patients have a notably higher recognition of p314 by IgG1 and IgG3.
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Anticorpos Antiprotozoários , Biomarcadores , Malária Vivax , Proteína 1 de Superfície de Merozoito , Plasmodium vivax , Humanos , Malária Vivax/imunologia , Malária Vivax/sangue , Malária Vivax/parasitologia , Malária Vivax/transmissão , Malária Vivax/diagnóstico , Proteína 1 de Superfície de Merozoito/imunologia , Plasmodium vivax/imunologia , Biomarcadores/sangue , Anticorpos Antiprotozoários/imunologia , Anticorpos Antiprotozoários/sangue , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Peptídeos/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Adulto Jovem , Adolescente , Sequência de AminoácidosRESUMO
The human malaria-Aotus monkey model has served the malaria research community since its inception in 1966 at the Gorgas Memorial Laboratory (GML) in Panama. Spanning over five decades, this model has been instrumental in evaluating the in vivo efficacy and pharmacokinetics of a wide array of candidate antimalarial drugs, whether used singly or in combination. The animal model could be infected with drug-resistant and susceptible Plasmodium falciparum and Plasmodium vivax strains that follow a characteristic and reproducible course of infection, remarkably like human untreated and treated infections. Over the years, the model has enabled the evaluation of several synthetic and semisynthetic endoperoxides, for instance, artelinic acid, artesunate, artemether, arteether, and artemisone. These compounds have been evaluated alone and in combination with long-acting partner drugs, commonly referred to as artemisinin-based combination therapies, which are recommended as first-line treatment against uncomplicated malaria. Further, the model has also supported the evaluation of the primaquine analog tafenoquine against blood stages of P. vivax, contributing to its progression to clinical trials and eventual approval. Besides, the P. falciparum/Aotus model at GML has also played a pivotal role in exploring the biology, immunology, and pathogenesis of malaria and in the characterization of drug-resistant P. falciparum and P. vivax strains. This minireview offers a historical overview of the most significant contributions made by the Panamanian owl monkey (Aotus lemurinus lemurinus) to malaria chemotherapy research.
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Antimaláricos , Artemisininas , Modelos Animais de Doenças , Animais , Antimaláricos/uso terapêutico , Antimaláricos/farmacocinética , Antimaláricos/farmacologia , Artemisininas/uso terapêutico , Artemisininas/farmacologia , Humanos , Panamá , Aotidae , Plasmodium falciparum/efeitos dos fármacos , Malária/tratamento farmacológico , Plasmodium vivax/efeitos dos fármacos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Artesunato/uso terapêutico , Artesunato/farmacologia , Artesunato/farmacocinética , Malária Vivax/tratamento farmacológico , Malária Vivax/parasitologia , História do Século XX , AminoquinolinasRESUMO
In malaria parasites, the erythrocyte binding-like proteins (EBL) are a family of invasion proteins that are attractive vaccine targets. In the case of Plasmodium vivax, the widespread malaria parasite, blood-stage vaccines have been largely focused on a single EBL candidate, the Duffy binding-like domain (DBL) of the Duffy binding protein (DBPII), due to its well-characterized role in the reticulocyte invasion. A novel P. vivax EBL family member, the Erythrocyte binding protein (EBP2, also named EBP or DBP2), binds preferentially to reticulocytes and may mediate an alternative P. vivax invasion pathway. To gain insight into the natural genetic diversity of the DBL domain of EBP2 (region II; EBP2-II), we analyzed ebp2-II gene sequences of 71 P. vivax isolates collected in different endemic settings of the Brazilian Amazon rainforest, where P. vivax is the predominant malaria-associated species. Although most of the substitutions in the ebp2-II gene were non-synonymous and suggested positive selection, the results showed that the DBL domain of the EBP2 was much less polymorphic than that of DBPII. The predominant EBP2 haplotype in the Amazon region corresponded to the C127 reference sequence first described in Cambodia (25% C127-like haplotype). An overview of ebp2-II gene sequences available at GenBank (n = 352) from seven countries (Cambodia, Madagascar, Myanmar, PNG, South Korea, Thailand, Vietnam) confirmed the C127-like haplotype as highly prevalent worldwide. Two out of 43 haplotypes (5 to 20 inferred per country) showed a global frequency of 60%. The results presented here open new avenues of research pursuit while suggesting that a vaccine based on the DBL domain of EBP2 should target a few haplotypes for broad coverage.
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Variação Genética , Malária Vivax , Plasmodium vivax , Proteínas de Protozoários , Plasmodium vivax/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/química , Malária Vivax/parasitologia , Humanos , Floresta Úmida , Filogenia , Haplótipos , Antígenos de Protozoários/genética , Domínios Proteicos , Receptores de Superfície CelularRESUMO
BACKGROUND: Plasmodium vivax relapses due to dormant liver hypnozoites can be prevented with primaquine. However, the dose must be adjusted in individuals with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. In French Guiana, assessment of G6PD activity is typically delayed until day (D)14 to avoid the risk if misclassification. This study assessed the kinetics of G6PD activity throughout P. vivax infection to inform the timing of treatment. METHODS: For this retrospective monocentric study, data on G6PD activity between D1 and D28 after treatment initiation with chloroquine or artemisinin-based combination therapy were collected for patients followed at Cayenne Hospital, French Guiana, between January 2018 and December 2020. Patients were divided into three groups based on the number of available G6PD activity assessments: (i) at least two measurements during the P. vivax malaria infection; (ii) two measurements: one during the current infection and one previously; (iii) only one measurement during the malaria infection. RESULTS: In total, 210 patients were included (80, 20 and 110 in groups 1, 2 and 3, respectively). Data from group 1 showed that G6PD activity remained stable in each patient over time (D1, D3, D7, D14, D21, D28). None of the patients with normal G6PD activity during the initial phase (D1-D3) of the malaria episode (n = 44) was categorized as G6PD-deficient at D14. Patients with G6PD activity < 80% at D1 or D3 showed normal activity at D14. Sex and reticulocyte count were statistically associated with G6PD activity variation. In the whole sample (n = 210), no patient had severe G6PD deficiency (< 10%) and only three between 10 and 30%, giving a G6PD deficiency prevalence of 1.4%. Among the 100 patients from group 1 and 2, 30 patients (26.5%) were lost to follow-up before primaquine initiation. CONCLUSIONS: In patients treated for P. vivax infection, G6PD activity did not vary over time. Therefore, G6PD activity on D1 instead of D14 could be used for primaquine dose-adjustment. This could allow earlier radical treatment with primaquine, that could have a public health impact by decreasing early recurrences and patients lost to follow-up before primaquine initiation. This hypothesis needs to be confirmed in larger prospective studies.
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Antimaláricos , Glucosefosfato Desidrogenase , Malária Vivax , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Cloroquina/uso terapêutico , Guiana Francesa/epidemiologia , Glucosefosfato Desidrogenase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/complicações , Cinética , Malária Vivax/tratamento farmacológico , Plasmodium vivax/efeitos dos fármacos , Plasmodium vivax/fisiologia , Primaquina/uso terapêutico , Estudos Retrospectivos , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Plasmodium vivax represents the most geographically widespread human malaria parasite affecting civilian and military populations in endemic areas. Targeting the pre-erythrocytic (PE) stage of the parasite life cycle is especially appealing for developing P. vivax vaccines as it would prevent disease and transmission. Here, naturally acquired immunity to a panel of P. vivax PE antigens was explored, which may facilitate vaccine development and lead to a better understanding of naturally acquired PE immunity. METHODS: Twelve P. vivax PE antigens orthologous to a panel of P. falciparum antigens previously identified as highly immunogenic in protected subjects after immunization with radiation attenuated sporozoites (RAS) were used for evaluation of humoral and cellular immunity by ELISA and IFN-γ ELISpot. Samples from P. vivax infected individuals (n = 76) from a low endemic malaria region in the Peruvian Amazon Basin were used. RESULTS: In those clinical samples, all PE antigens evaluated showed positive IgG antibody reactivity with a variable prevalence of 58-99% in recently P. vivax diagnosed patients. The magnitude of the IgG antibody response against PE antigens was lower compared with blood stage antigens MSP1 and DBP-II, although antibody levels persisted better for PE antigens (average decrease of 6% for PE antigens and 43% for MSP1, p < 0.05). Higher IgG antibodies was associated with one or more previous malaria episodes only for blood stage antigens (p < 0.001). High IgG responders across PE and blood stage antigens showed significantly lower parasitaemia compared to low IgG responders (median 1,921 vs 4,663 par/µl, p < 0.05). In a subgroup of volunteers (n = 17),positive IFN-γ T cell response by ELISPOT was observed in 35% vs 9-35% against blood stage MSP1 and PE antigens, respectively, but no correlation with IgG responses. CONCLUSIONS: These results demonstrate clear humoral and T cell responses against P. vivax PE antigens in individuals naturally infected with P. vivax. These data identify novel attractive PE antigens suitable for use in the potential development and selection of new malaria vaccine candidates which can be used as a part of malaria prevention strategies in civilian and military populations living in P. vivax endemic areas.
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Antígenos de Protozoários , Malária Vivax , Plasmodium vivax , Proteínas de Protozoários , Plasmodium vivax/imunologia , Peru/epidemiologia , Humanos , Malária Vivax/imunologia , Malária Vivax/epidemiologia , Adulto , Masculino , Adulto Jovem , Adolescente , Feminino , Pessoa de Meia-Idade , Proteínas de Protozoários/imunologia , Antígenos de Protozoários/imunologia , Imunoglobulina G/sangue , Anticorpos Antiprotozoários/sangue , Ensaio de Imunoadsorção Enzimática , Criança , Idoso , ELISPOTRESUMO
Malaria remains a public health challenge. Since many control strategies have proven ineffective in eradicating this disease, new strategies are required, among which the design of a multivalent vaccine stands out. However, the effectiveness of this strategy has been hindered, among other reasons, by the genetic diversity observed in parasite antigens. In Plasmodium vivax, the Erythrocyte Binding Protein (PvEBP, also known as DBP2) is an alternate ligand to Duffy Binding Protein (DBP); given its structural resemblance to DBP, EBP/DBP2 is proposed as a promising antigen for inclusion in vaccine design. However, the extent of genetic diversity within the locus encoding this protein has not been comprehensively assessed. Thus, this study aimed to characterize the genetic diversity of the locus encoding the P. vivax EBP/DBP2 protein and to determine the evolutionary mechanisms modulating this diversity. Several intrapopulation genetic variation parameters were estimated using 36 gene sequences of PvEBP/DBP2 from Colombian P. vivax clinical isolates and 186 sequences available in databases. The study then evaluated the worldwide genetic structure and the evolutionary forces that may influence the observed patterns of genetic variation. It was found that the PvEBP/DBP2 gene exhibits one of the lowest levels of genetic diversity compared to other vaccine-candidate antigens. Four major haplotypes were shared worldwide. Analysis of the protein's 3D structure and epitope prediction identified five regions with potential antigenic properties. The results suggest that the PvEBP/DBP2 protein possesses ideal characteristics to be considered when designing a multivalent effective antimalarial vaccine against P. vivax.
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Antígenos de Protozoários , Variação Genética , Vacinas Antimaláricas , Malária Vivax , Plasmodium vivax , Proteínas de Protozoários , Plasmodium vivax/genética , Plasmodium vivax/imunologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Humanos , Vacinas Antimaláricas/imunologia , Vacinas Antimaláricas/genética , Malária Vivax/prevenção & controle , Malária Vivax/parasitologia , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Colômbia , Filogenia , Receptores de Superfície CelularRESUMO
Malaria caused byPlasmodium vivaxis a pressing public health problem in tropical and subtropical areas.However, little progress has been made toward developing a P. vivaxvaccine, with only three candidates being tested in clinical studies. We previously reported that one chimeric recombinant protein (PvCSP-All epitopes) containing the conserved C-terminus of the P. vivax Circumsporozoite Protein (PvCSP), the three variant repeat domains, and aToll-like receptor-3 agonist,Poly(I:C), as an adjuvant (polyinosinic-polycytidylic acid, a dsRNA analog mimicking viral RNA), elicits strong antibody-mediated immune responses in mice to each of the three allelic forms of PvCSP. In the present study, a pre-clinical safety evaluation was performed to identify potential local and systemic toxic effects of the PvCSP-All epitopes combined with the Poly-ICLC (Poly I:C plus poly-L-lysine, Hiltonol®) or Poly-ICLC when subcutaneously injected into C57BL/6 mice and New Zealand White Rabbits followed by a 21-day recovery period. Overall, all observations were considered non-adverse and were consistent with the expected inflammatory response and immune stimulation following vaccine administration. High levels of vaccine-induced specific antibodies were detected both in mice and rabbits. Furthermore, mice that received the vaccine formulation were protected after the challenge with Plasmodium berghei sporozoites expressing CSP repeats from P. vivax sporozoites (Pb/Pv-VK210). In conclusion, in these non-clinical models, repeated dose administrations of the PvCSP-All epitopes vaccine adjuvanted with a Poly-ICLC were immunogenic, safe, and well tolerated.
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Carboximetilcelulose Sódica/análogos & derivados , Vacinas Antimaláricas , Malária Vivax , Polilisina/análogos & derivados , Camundongos , Animais , Coelhos , Malária Vivax/prevenção & controle , Poli I-C , Plasmodium vivax , Proteínas de Protozoários/genética , Camundongos Endogâmicos C57BL , Adjuvantes Imunológicos , Proteínas Recombinantes , Epitopos , Anticorpos AntiprotozoáriosRESUMO
BACKGROUND: Malarial infections are often missed by microscopy, and most parasite carriers are asymptomatic in low-endemicity settings. Whether parasite detectability and its ability to elicit symptoms change as transmission declines remains unclear. METHODS: We performed a prospective panel survey with repeated measurements on the same participants over 12 months to investigate whether Plasmodium vivax detectability by microscopy and risk of symptoms upon infection varied during a community-wide larviciding intervention in the Amazon basin of Brazil that markedly reduced vector density. We screened 1096 to 1400 residents in the intervention site for malaria by microscopy and quantitative TaqMan assays at baseline and twice during intervention. RESULTS: We found that more P vivax infections than expected from their parasite densities measured by TaqMan assays were missed by microscopy as transmission decreased. At lower transmission, study participants appeared to tolerate higher P vivax loads without developing symptoms. We hypothesize that changes in the ratio between circulating parasites and those that accumulate in the bone marrow and spleen, by avoiding peripheral blood microscopy detection, account for decreased parasite detectability and lower risk of symptoms under low transmission. CONCLUSIONS: P vivax infections are more likely to be subpatent and remain asymptomatic as malaria transmission decreases.
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Malária Falciparum , Malária Vivax , Malária , Humanos , Malária Vivax/parasitologia , Brasil/epidemiologia , Estudos Prospectivos , Malária Falciparum/parasitologia , Prevalência , Plasmodium vivax , Plasmodium falciparumRESUMO
Primaquine (PQ) is the main drug used to eliminate dormant liver stages and prevent relapses in Plasmodium vivax malaria. It also has an effect on the gametocytes of Plasmodium falciparum; however, it is unclear to what extent PQ affects P. vivax gametocytes. PQ metabolism involves multiple enzymes, including the highly polymorphic CYP2D6 and the cytochrome P450 reductase (CPR). Since genetic variability can impact drug metabolism, we conducted an evaluation of the effect of CYP2D6 and CPR variants on PQ gametocytocidal activity in 100 subjects with P. vivax malaria. To determine gametocyte density, we measured the levels of pvs25 transcripts in samples taken before treatment (D0) and 72 hours after treatment (D3). Generalized estimating equations (GEEs) were used to examine the effects of enzyme variants on gametocyte densities, adjusting for potential confounding factors. Linear regression models were adjusted to explore the predictors of PQ blood levels measured on D3. Individuals with the CPR mutation showed a smaller decrease in gametocyte transcript levels on D3 compared to those without the mutation (P = 0.02, by GEE). Consistent with this, higher PQ blood levels on D3 were associated with a lower reduction in pvs25 transcripts. Based on our findings, the CPR variant plays a role in the persistence of gametocyte density in P. vivax malaria. Conceptually, our work points to pharmacogenetics as a non-negligible factor to define potential host reservoirs with the propensity to contribute to transmission in the first days of CQ-PQ treatment, particularly in settings and seasons of high Anopheles human-biting rates.
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Antimaláricos , Artemisininas , Malária Falciparum , Malária Vivax , Malária , Humanos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Malária Vivax/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , NADPH-Ferri-Hemoproteína Redutase , Cloroquina/farmacologia , Citocromo P-450 CYP2D6/genética , Artemisininas/farmacologia , Primaquina/farmacologia , Primaquina/uso terapêutico , Malária/tratamento farmacológico , Plasmodium falciparum , Plasmodium vivax/genéticaRESUMO
Presentación del caso. Paciente masculino de origen guatemalteco con historia de fiebre alta de tipo intermitente, mialgias, artralgias, debilidad generalizada, mareo y vómito de contenido gástrico. Fue tratado inicialmente en un hospital privado con diagnóstico de síndrome febril agudo y referido a un hospital de la red nacional con diagnóstico de dengue con signos de alarma, al tercer día de estancia hospitalaria se diagnostica como un caso de malaria importado por Plasmodium vivax. Intervención terapéutica. Se le dio tratamiento antimalárico con cloroquina y primaquina. Evolución clínica. Presentó mejoría clínica y las pruebas de laboratorio de control reportaron resultados negativos para Plasmodium vivax
Case presentation. Male patient of Guatemalan origin with history of intermittent high fever, myalgia, arthralgia, generalized weakness, dizziness, and vomiting of gastric contents. He was initially treated in a private hospital with a diagnosis of acute febrile illness and referred to a national network hospital with a diagnosis of dengue with warning signs. On the third day of hospital stay a diagnosis of an imported malaria case by Plasmodium vivax was presented. Treatment. The patient was given antimalarial treatment consisting of chloroquine and primaquine. Outcome. The patient presented clinical improvement, and control laboratory tests were negative for Plasmodium vivax.
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Humanos , Masculino , Doenças Transmitidas por Vetores , El SalvadorRESUMO
Malaria is the deadliest parasitic disease in the world. Traditional control measures have become less effective; hence, there is a need to explore alternative strategies, such as antimalarial vaccines. However, designing an anti-Plasmodium vivax vaccine is considered a challenge due to the complex parasite biology and the antigens' high genetic diversity. Recently, the sporozoite invasion-associated protein 2 (SIAP2) has been suggested as a potential antigen to be considered in vaccine design due to its significance during hepatocyte invasion. However, its use may be limited by the incomplete understanding of gene/protein diversity. Here, the genetic diversity of pvsiap2 using P. vivax DNA samples from Colombia was assessed. Through PCR amplification and sequencing, we compared the Colombian sequences with available worldwide sequences, revealing that pvsiap2 displays low genetic diversity. Molecular evolutionary analyses showed that pvsiap2 appears to be influenced by directional selection. Moreover, the haplotypes found differ by a few mutational steps and several of them were shared between different geographical areas. On the other hand, several conserved regions within PvSIAP2 were predicted as potential B-cell or T-cell epitopes. Considering these characteristics and its role in hepatocyte invasion, the PvSIAP2 protein emerges as a promising antigen to be considered in a multi-antigen-multi-stage (multivalent) fully effective vaccine against P. vivax malaria.
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Vacinas Antimaláricas , Malária Vivax , Humanos , Plasmodium vivax/genética , Vacinas Antimaláricas/genética , Antígenos de Protozoários/genética , Proteínas de Protozoários/genética , Variação Genética , Malária Vivax/prevenção & controle , Malária Vivax/parasitologia , Seleção GenéticaRESUMO
ABSTRACT Acquired thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening disorder characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ damage. We present the case of a 71-year-old man initially diagnosed with malaria-like symptoms and displaying markers of microangiopathic hemolytic anemia, severe thrombocytopenia, renal injury, and neurological impairment. Despite antimalarial treatment, acquired TTP was suspected. Plasma exchange and immunosuppressive therapy led to clinical improvement, normalizing the platelet count and hemolytic profile. Diagnostic confirmation revealed significantly reduced ADAMTS13 levels. Following the proposed treatment, the patient's ADAMTS13 levels normalized. This case illustrates acquired TTP linked to uncomplicated Plasmodium vivax malaria.
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ABSTRACT Background: Malaria is a major global public health issue with varying epidemiologies across countries. In Colombia, it is a priority endemic-epidemic event included in the national public health policy. However, evidence demonstrating nationwide variations in the disease behavior is limited. This study aimed to analyze changes in the levels and distribution of endemic-epidemic malaria transmission in the eco-epidemiological regions of Colombia from 1978 to 1999 and 2000 to 2021. Methods: We conducted a comprehensive time-series study using official secondary data on malaria-associated morbidity and mortality in Colombia from 1978 to 2021. Temporal-spatial and population variables were analyzed, and the absolute and relative frequency measures of general and regional morbidity and mortality were estimated. Results: We observed an 18% reduction in malaria endemic cases between the two study periods. The frequency and severity of the epidemic transmission of malaria varied less and were comparable across both periods. A shift was observed in the frequency of parasitic infections, with a tendency to match and increase infections by Plasmodium falciparum. The risk of malaria transmission varied significantly among the eco-epidemiological regions during both study periods. This study demonstrated a sustained decrease of 78% in malarial mortality. Conclusions: Although the endemic components of malaria decreased slightly between the two study periods, the epidemic pattern persisted. There were significant variations in the risk of transmission across the different eco-epidemiological regions. These findings underscore the importance of targeted public health interventions in reducing malarial morbidity and mortality rates in Colombia.
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Circadian behavioral patterns in mosquitoes can be observed through their locomotor activity, which includes fundamental behaviors such as foraging, mating, and oviposition. These habits, which are fundamental to the life cycle of Anopheles mosquitoes, are closely related to pathogen transmission to humans. While rhythmic cycles of locomotor activity have been described in Anopheles species, no studies have been conducted on Anopheles darlingi species, the main malaria vector in the Amazon region. The aim of this study was to investigate how insemination status, blood meal, and Plasmodium vivax infection affect the locomotor activity of An. darlingi. The experiments were performed with 3- to 10-day-old An. darlingi females, which had been fed with 15% honey solution. These mosquitoes were obtained from the Malaria Vector Production and Infection Platform (PIVEM)/FIOCRUZ-RO. The experimental groups were divided into four categories: virgin vs. inseminated, unfed virgin vs. blood-fed virgin, unfed inseminated vs. blood-fed inseminated, and infected blood vs. uninfected blood. Locomotor activity was monitored using the Flybox equipment, capturing images that were subsequently converted into video to measure the insect activity, using PySoLo software. The periodicity and rhythmicity of mosquito locomotor activity were analyzed using MatLab® software. The locomotor activity of An. darlingi females showed a nocturnal and bimodal pattern under LD conditions. When comparing the insemination states and blood meal, there was a reduction in the locomotor activity in inseminated and blood-fed females. However, the P. vivax+ infection did not increase locomotor activity of An. darlingi species.
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Anopheles , Malária Vivax , Malária , Humanos , Animais , Feminino , Plasmodium vivax , Mosquitos Vetores , Inseminação , Comportamento AlimentarRESUMO
Background: Malaria remains a severe parasitic disease, posing a significant threat to public health and hindering economic development in sub-Saharan Africa. Ethiopia, a malaria endemic country, is facing a resurgence of the disease with a steadily rising incidence. Conventional diagnostic methods, such asmicroscopy, have become less effective due to low parasite density, particularly among Duffy-negative human populations in Africa. To develop comprehensive control strategies, it is crucial to generate data on the distribution and clinical occurrence of Plasmodium vivax and P. falciparum infections in regions where the disease is prevalent. This study assessed Plasmodium infections and Duffy antigen genotypes in febrile patients in Ethiopia. Methods: Three hundred febrile patients visiting four health facilities in Jimma town of southwestern Ethiopia were randomly selected during the malaria transmission season (Apr-Oct). Sociodemographic information was collected, and microscopic examination was performed for all study participants. Plasmodiumspecies and parasitemia as well as the Duffy genotype were assessed by quantitative polymerase chain reaction (qPCR) for all samples. Data were analyzed using Fisher's exact test and kappa statistics. Results: The Plasmodium infection rate by qPCR was 16% (48/300) among febrile patients, of which 19 (39.6%) were P. vivax, 25 (52.1%) were P. falciparum, and 4 (8.3%) were mixed (P. vivax and P. falciparum) infections. Among the 48 qPCR-positive samples, 39 (13%) were negative by microscopy. The results of bivariate logistic regression analysis showed that agriculture-related occupation, relapse and recurrence were significantly associated withPlasmodium infection (P<0.001). Of the 300 febrile patients, 85 (28.3%) were Duffy negative, of whom two had P. vivax, six had P. falciparum, and one had mixed infections.Except for one patient with P. falciparum infection, Plasmodium infections in Duffy-negative individuals were all submicroscopic with low parasitemia. Conclusions: The present study revealed a high prevalence of submicroscopic malaria infections. Plasmodium vivax infections in Duffy-negative individuals were not detected due to low parasitemia. Here, we recommend an improved molecular diagnostic tool to detect and characterize plasmodium infections, with the goal of quantifyingP. vivax infection in Duffy-negative individuals.
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Migration is an important risk factor for malaria transmission for malaria transmission, creating networks that connect Plasmodium between communities. This study aims to understand the timing of why people in the Peruvian Amazon migrated and how characteristics of these migrants are associated with malaria risk. A cohort of 2,202 participants was followed for three years (July 2006 - October 2009), with thrice-weekly active surveillance to record infection and recent travel, which included travel destination(s) and duration away. Migration occurred more frequently in the dry season, but the 7-day rolling mean (7DRM) streamflow was positively correlated with migration events (OR 1.25 (95% CI: 1.138, 1.368)). High-frequency and low-frequency migrant populations reported 9.7 (IRR 7.59 (95% CI:.381, 13.160)) and 4.1 (IRR 2.89 (95% CI: 1.636, 5.099)) times more P. vivax cases than those considered non-migrants and 30.7 (IRR 32.42 (95% CI: 7.977, 131.765)) and 7.4 (IRR 7.44 (95% CI: 1.783, 31.066)) times more P. falciparum cases, respectively. High-frequency migrants employed in manual labour within their community were at 2.45 (95% CI: 1.113, 5.416) times higher risk than non-employed low-frequency migrants. This study confirms the importance of migration for malaria risk as well as factors increasing risk among the migratory community, including, sex, occupation, and educational status.
Assuntos
Malária Falciparum , Malária Vivax , Malária , Humanos , Malária Vivax/epidemiologia , Malária Falciparum/epidemiologia , Plasmodium vivax , Plasmodium falciparum , Peru/epidemiologia , Estudos Prospectivos , Malária/epidemiologiaRESUMO
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 adversosRESUMO
Malaria is the leading human parasitosis and is transmitted through the bite of anopheline mosquitoes infected with parasites of the genus Plasmodium spp. Among the seven species that cause malaria in humans, Plasmodium vivax is the most prevalent species in Latin America. In recent years, there have been an increasing number of reports of clinical complications caused by P. vivax infections, which were previously neglected and underestimated. P. vivax biology remains with large gaps. The emergence of next-generation sequencing technology has ensured a breakthrough in species knowledge. Coupled with this, the deposition of the P. vivax Sal-1 reference genome allowed an increase in transcriptomics projects by accessing messenger RNA. Thus, the regulation of differential gene expression according to the parasite life stage was verified, and several expressed genes were linked to different biological functions. Today, with the progress associated with RNA sequencing technologies, it is possible to detect nuances and obtain robust results. Discoveries provided by transcriptomic studies allow us to understand topics such as RNA expression and regulation and proteins and metabolic pathways involved during different stages of the parasite life cycle. The information obtained enables a better comprehension of immune system evasion mechanisms; invasion and adhesion strategies used by the parasite; as well as new vaccine targets, potential molecular markers, and others therapeutic targets. In this review, we provide new insights into P. vivax biology by summarizing recent findings in transcriptomic studies.
Assuntos
Malária Vivax , Malária , Parasitos , Animais , Humanos , Plasmodium vivax/genética , Malária Vivax/genética , Malária Vivax/parasitologia , Perfilação da Expressão GênicaRESUMO
BACKGROUND: Plasmodium vivax is the second most important cause of human malaria worldwide, and accounts for the majority of malaria cases in South America. A high-quality reference genome exists for Papua Indonesia (PvP01) and Thailand (PvW1), but is lacking for South America. A reference genome specifically for South America would be beneficial though, as P. vivax is a genetically diverse parasite with geographical clustering. RESULTS: This study presents a new high-quality assembly of a South American P. vivax isolate, referred to as PvPAM (P. vivax Peruvian AMazon). The genome was obtained from a low input patient sample from the Peruvian Amazon and sequenced using PacBio technology, resulting in a highly complete assembly with 6497 functional genes. Telomeric ends were present in 17 out of 28 chromosomal ends, and additional (sub)telomeric regions are present in 12 unassigned contigs. A comparison of multigene families between PvPAM and the PvP01 genome revealed remarkable variation in vir genes, and the presence of merozoite surface proteins (MSP) 3.6 and 3.7. Three dhfr and dhps drug resistance associated mutations are present in PvPAM, similar to those found in other Peruvian isolates. Mapping of publicly available South American whole genome sequencing (WGS) data to PvPAM resulted in significantly fewer variants and truncated reads compared to the use of PvP01 or PvW1 as reference genomes. To minimize the number of core genome variants in non-South American samples, PvW1 is most suited for Southeast Asian isolates, both PvPAM and PvW1 are suited for South Asian isolates, and PvPAM is recommended for African isolates. Interestingly, non-South American samples still contained the least subtelomeric variants when mapped to PvPAM, indicating high quality of the PvPAM subtelomeric regions. CONCLUSIONS: Our findings show that the PvPAM reference genome more accurately represents South American P. vivax isolates in comparison to PvP01 and PvW1. In addition, PvPAM has a high level of completeness, and contains a similar number of annotated genes as PvP01 or PvW1. The PvPAM genome therefore will be a valuable resource to improve future genomic analyses on P. vivax isolates from the South American continent.