RESUMO
BACKGROUND: More than 95% of malaria transmission in Brazil occurs in the Legal Amazon Region, which in 2010 recorded around 333,429 cases reported in the Epidemiological Surveillance Information System-Malaria (Sivep_malaria), presenting an annual parasitic incidence (IPA) of 13.1 cases/1000 inhabitants. METHODS: This was a descriptive study that measured the community prevalence of Plasmodium infection and its relationship with land use in Três Fronteiras District, Colniza Municipality, Mato Grosso State. Data were collected during household visits in July 2011, with blood collection from finger pricks for the preparation of thick smear slides, and completion of a standardized case notification form. A georeferenced database was analysed, with land use evaluated as categorical variables. A kernel density map was built to show the density of cases and their location. RESULTS: Of the 621 respondents, 68(11%) had Plasmodium infection: 39 (57.4%) with Plasmodium vivax, 27(39.7%) with Plasmodium falciparum and two (2.9%) with mixed infections. Among infected individuals, 49 (72.1%) were men. Cases of malaria were distributed over the district, with greater occurrence of cases per household in open areas close to the mining company and artisanal mining sites. The was a greater density of cases located in the gold mining region. CONCLUSION: Transmission of malaria in Três Fronteiras District has a heterogeneous distribution. Individuals residing in mining and timber extraction sites have increased occurrence of Plasmodium infection.
Assuntos
Malária Falciparum , Malária Vivax , População Rural , Brasil/epidemiologia , Humanos , Feminino , Masculino , Adolescente , Adulto , População Rural/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto Jovem , Criança , Pré-Escolar , Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Prevalência , Lactente , Idoso , Incidência , Idoso de 80 Anos ou mais , Plasmodium vivax , Malária/epidemiologia , Malária/transmissãoRESUMO
Malaria is a public health problem and the cases diagnosed in the capital of Roraima, Brazil, show potential to characterize the burden of the disease in the state. This study aimed to describe the epidemiological, clinical, and laboratory aspects of malaria cases diagnosed in Boa Vista. For this purpose, a descriptive, cross-sectional study was conducted in two health units in the city, with individuals diagnosed and who agreed to respond the questionnaire. Of the total of 206 participants, characterized as men, mixed-race, and young, 96% (198) reported participating in illegal mining activity. Among the group of miners, 66% (131) came from other states of Brazil or other countries. The mines were mainly located in the Yanomami territory in Roraima. Plasmodium vivax infection occurred in 74% (153) of participants. In the miner's group, hospitalizations for severe malaria, previous malaria attacks, and delays in treatment after the onset of symptoms were reported. Although 73% (145) of miners reported knowing how malaria was transmitted, only 54% (107) used mosquito nets or repellents. The use of Artecom and chloroquine by miners is not for the complete treatment but only to relieve symptoms for returning to gold mines, highlighting the importance of molecular surveillance to antimalarial resistance. Indigenous peoples are considered vulnerable to malaria and miners promotes the increase of malaria in Roraima Indigenous Lands. Therefore, access to diagnosis and treatment in Indigenous areas invaded by miners is imperative to confront this disease that ravages Indigenous communities and threatens public health on a large scale to achieve the goal of eliminating malaria in the state.
Assuntos
Mineração , Humanos , Brasil/epidemiologia , Masculino , Estudos Transversais , Adulto , Adulto Jovem , Feminino , Adolescente , Pessoa de Meia-Idade , Malária Vivax/epidemiologia , Malária Vivax/prevenção & controle , Malária/epidemiologia , Malária/prevenção & controle , Indígenas Sul-Americanos/estatística & dados numéricosRESUMO
BACKGROUND: Plasmodium vivax is the most predominant malaria species in Latin America, constituting 71.5% of malaria cases in 2021. With several countries aiming for malaria elimination, it is crucial to prioritize effectiveness of national control programs by optimizing the utilization of available resources and strategically implementing necessary changes. To support this, there is a need for innovative approaches such as genomic surveillance tools that can investigate changes in transmission intensity, imported cases and sources of reintroduction, and can detect molecular markers associated with drug resistance. METHODOLOGY/PRINCIPAL FINDINGS: Here, we apply a modified highly-multiplexed deep sequencing assay: Pv AmpliSeq v2 Peru. The tool targets a newly developed 41-SNP Peru barcode for parasite population analysis within Peru, the 33-SNP vivaxGEN-geo panel for country-level classification, and 11 putative drug resistance genes. It was applied to 230 samples from the Peruvian Amazon (2007-2020), generating baseline surveillance data. We observed a heterogenous P. vivax population with high diversity and gene flow in peri-urban areas of Maynas province (Loreto region) with a temporal drift using all SNPs detected by the assay (nSNP = 2909). In comparison, in an indigenous isolated area, the parasite population was genetically differentiated (FST = 0.07-0.09) with moderate diversity and high relatedness between isolates in the community. In a remote border community, a clonal P. vivax cluster was identified, with distinct haplotypes in drug resistant genes and ama1, more similar to Brazilian isolates, likely representing an introduction of P. vivax from Brazil at that time. To test its applicability for Latin America, we evaluated the SNP Peru barcode in P. vivax genomes from the region and demonstrated the capacity to capture local population clustering at within-country level. CONCLUSIONS/SIGNIFICANCE: Together this data shows that P. vivax transmission is heterogeneous in different settings within the Peruvian Amazon. Genetic analysis is a key component for regional malaria control, offering valuable insights that should be incorporated into routine surveillance.
Assuntos
Malária Vivax , Plasmodium vivax , Polimorfismo de Nucleotídeo Único , Plasmodium vivax/genética , Plasmodium vivax/isolamento & purificação , Plasmodium vivax/classificação , Peru/epidemiologia , Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Humanos , Resistência a Medicamentos/genética , Genoma de Protozoário , Sequenciamento de Nucleotídeos em Larga Escala , Monitoramento Epidemiológico , GenômicaRESUMO
BACKGROUND: Malaria remains a global health challenge, particularly in Peru's Loreto region. Despite ongoing efforts, high infection rates and asymptomatic cases perpetuate transmission. The Peruvian Ministry of Health's "Zero Malaria Plan" targets elimination. This novel study combines microscopic, molecular, and serological techniques to assess transmission intensity, identify epidemiological risk factors, and characterize species-specific patterns across villages. The findings aim to inform targeted interventions and support broader malaria elimination efforts in line with the Zero Malaria Plan initiative. METHODS: A cross-sectional malaria survey was conducted in the Zungarococha community, comprising the villages Llanchama (LL), Ninarumi (NI), Puerto Almendra (PA), and Zungarococha (ZG), using microscopic, molecular, and serological techniques to evaluate malaria transmission intensity. Statistical analysis, including multivariate-adjusted analysis, seroprevalence curves, and spatial clustering analysis, were performed to assess malaria prevalence, exposure, and risk factors. RESULTS: The survey revealed a high prevalence of asymptomatic infections (6% by microscopy and 18% by PCR), indicating that molecular methods are more sensitive for detecting asymptomatic infections. Seroprevalence varied significantly between villages, reflecting the heterogeneous malaria transmission dynamics. Multivariate analysis identified age, village, and limited bed net use as significant risk factors for malaria infection and species-specific exposure. Seroprevalence curves demonstrated community-specific patterns, with Llanchama and Puerto Almendra showing the highest seroconversion rates for both Plasmodium species. CONCLUSIONS: The study highlights the diverse nature of malaria transmission in the Loreto region, particularly nothing the pronounced heterogeneity as transmission rates decline, especially in residual malaria scenarios. The use of molecular and serological techniques enhances the detection of current infections and past exposure, aiding in the identification of epidemiological risk factors. These findings underscore the importance of using molecular and serological tools to characterize malaria transmission patterns in low-endemic areas, which is crucial for planning and implementing targeted interventions and elimination strategies. This is particularly relevant for initiatives like the Zero Malaria Plan in the Peruvian Amazon.
Assuntos
Malária , Peru/epidemiologia , Estudos Transversais , Humanos , Pré-Escolar , Adulto , Adolescente , Masculino , Feminino , Criança , Pessoa de Meia-Idade , Adulto Jovem , Lactente , Idoso , Estudos Soroepidemiológicos , Prevalência , Fatores de Risco , Malária/transmissão , Malária/epidemiologia , Malária Falciparum/transmissão , Malária Falciparum/epidemiologia , Idoso de 80 Anos ou mais , Malária Vivax/transmissão , Malária Vivax/epidemiologia , Recém-NascidoAssuntos
Antimaláricos , Deficiência de Glucosefosfato Desidrogenase , Hemólise , Primaquina , Humanos , Primaquina/efeitos adversos , Primaquina/uso terapêutico , Deficiência de Glucosefosfato Desidrogenase/complicações , Hemólise/efeitos dos fármacos , Colômbia , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Masculino , Adulto , Malária Vivax/tratamento farmacológicoRESUMO
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.
Assuntos
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
BACKGROUND: Plasmodium vivax is the main causative agent of malaria in Panama. However, the prevalence of asymptomatic infections in the different endemic regions remains unknown. Understanding the epidemiological behavior of asymptomatic infections is essential for the elimination of malaria. This study aimed to determine the prevalence of asymptomatic malarial infections in one of the main endemic regions of Panama using multiplex real-time reverse transcription RT-MqPCR. METHODS: A cross-sectional study was conducted in three communities in the Guna Yala Comarca. A total of 551 thick blood smears and their respective samples on filter paper were collected from volunteers of different ages and sexes from June 20 to 25, 2016. Infections by the Plasmodium spp. were diagnosed using microscopy and RT-MqPCR. All statistical analyses were performed using the R software. RESULTS: The average prevalence of asymptomatic infections by P. vivax in the three communities detected by RT-MqPCR was 9.3%, with Ukupa having the highest prevalence (13.4%), followed by Aidirgandi (11.1%) and Irgandi (3.3%). A total of 74 samples were diagnosed as asymptomatic infections using RT-MqPCR. Light microscopy (LM) detected that 17.6% (13/74) of the asymptomatic samples and 82.4% (61/74) were diagnosed as false negatives. A 100% correlation was observed between samples diagnosed using LM and RT-MqPCR. A total of 52.7% (39/74) of the asymptomatic patients were female and 85.1% (63/74) were registered between the ages of 1 and 21 years. Factors associated with asymptomatic infection were community (aOR = 0.38 (95% CI 0.17-0.83), p < 0.001) and age aOR = 0.98 (95% CI 0.97-1.00), p < 0.05); F = 5.38; p < 0.05). CONCLUSIONS: This study provides novel evidence of the considerable prevalence of asymptomatic P. vivax infections in the endemic region of Kuna Yala, representing a new challenge that requires immediate attention from the National Malaria Program. The results of this study provide essential information for the health authorities responsible for developing new policies. Furthermore, it will allow program administrators to reorient and design effective malaria control strategies that consider asymptomatic infections as a fundamental part of malaria control and move towards fulfilling their commitment to eliminate it.
Assuntos
Malária Vivax , Plasmodium vivax , Humanos , Panamá/epidemiologia , Feminino , Masculino , Adulto , Estudos Transversais , Adolescente , Malária Vivax/epidemiologia , Malária Vivax/diagnóstico , Malária Vivax/parasitologia , Plasmodium vivax/genética , Plasmodium vivax/isolamento & purificação , Adulto Jovem , Criança , Pessoa de Meia-Idade , Prevalência , Infecções Assintomáticas/epidemiologia , Pré-Escolar , Povos Indígenas/genética , Lactente , Reação em Cadeia da Polimerase em Tempo Real/métodosRESUMO
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 SuperfícieRESUMO
Hard-to-reach communities represent Peru's main challenge for malaria elimination, but information about transmission in these areas is scarce. Here, we assessed Plasmodium vivax (Pv) and P. falciparum (Pf) transmission dynamics, resistance markers, and Pf hrp2/3 deletions in Nueva Jerusalén (NJ), a remote, indigenous community in the Peruvian Amazon with high population mobility. We collected samples from November 2019 to May 2020 by active (ACD) and passive case detection (PCD) in NJ. Parasites were identified with microscopy and PCR. Then, we analyzed a representative set of positive-PCR samples (Pv = 68, Pf = 58) using highly-multiplexed deep sequencing assays (AmpliSeq) and compared NJ parasites with ones from other remote Peruvian areas using population genetics indexes. The ACD intervention did not reduce malaria cases in the short term, and persistent malaria transmission was observed (at least one Pv infection was detected in 96% of the study days). In Nueva Jerusalen, the Pv population had modest genetic diversity (He = 0.27). Pf population had lower diversity (He = 0.08) and presented temporal clustering, one of these clusters linked to an outbreak in February 2020. Moreover, Pv and Pf parasites from NJ exhibited variable levels of differentiation (Pv Fst = 0.07-0.52 and Pf Fst = 0.11-0.58) with parasites from other remote areas. No artemisin resistance mutations but chloroquine (57%) and sulfadoxine-pyrimethamine (35-67%) were detected in NJ's Pf parasites. Moreover, pfhrp2/3 gene deletions were common (32-50% of parasites with one or both genes deleted). The persistent Pv transmission and the detection of a Pf outbreak with parasites genetically distinct from the local ones highlight the need for tailored interventions focusing on mobility patterns and imported infections in remote areas to eliminate malaria in the Peruvian Amazon.
Assuntos
Malária Falciparum , Malária Vivax , Plasmodium falciparum , Plasmodium vivax , Proteínas de Protozoários , Peru/epidemiologia , Humanos , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/genética , Plasmodium vivax/isolamento & purificação , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Malária Vivax/transmissão , Proteínas de Protozoários/genética , Feminino , Masculino , Criança , Adulto , Antimaláricos/uso terapêutico , Antimaláricos/farmacologia , Adolescente , Resistência a Medicamentos/genética , Pessoa de Meia-Idade , Povos Indígenas/genética , Adulto Jovem , Pré-Escolar , Genômica/métodos , Variação Genética , Antígenos de Protozoários/genéticaRESUMO
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.