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1.
Malar J ; 21(1): 255, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068577

RESUMO

BACKGROUND: Circulating myeloid-derived-suppressor-cells (MDSC) with immunosuppressive function are increased in human experimental Plasmodium falciparum infection, but have not been studied in clinical malaria. METHODS: Using flow-cytometry, circulating polymorphonuclear-MDSC were evaluated in cryopreserved samples from patients with uncomplicated Plasmodium vivax (n = 8) and uncomplicated (n = 4) and severe (n = 16) falciparum malaria from Papua, Indonesia. RESULTS: The absolute number of circulating polymorphonuclear-MDSC were significantly elevated in severe falciparum malaria patients compared to controls (n = 10). Polymorphonuclear-MDSC levels in uncomplicated vivax malaria were also elevated to levels comparable to that seen in severe falciparum malaria. CONCLUSION: Control of expansion of immunosuppressive MDSC may be important for development of effective immune responses in falciparum and vivax malaria.


Assuntos
Malária Falciparum , Malária Vivax , Malária , Células Supressoras Mieloides , Humanos , Indonésia , Malária/complicações , Plasmodium falciparum , Plasmodium vivax
2.
Biomed Pharmacother ; 149: 112874, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-36068770

RESUMO

The western Amazon basin is an important endemic area for malaria by P. vivax. In recent years, several reports showed the treatment failure with chloroquine, which can be related to resistance. The assessment of chloroquine resistance requires the evaluation of drug exposure, and when possible, the estimation of the pharmacokinetic parameters. However, there is no data on the pharmacokinetics of chloroquine in this endemic area. Moreover, the influence of the early reappearance of parasites in blood on the exposure to the drug was low exploited in the literature. The present study described the pharmacokinetic parameters of chloroquine in whole blood of adult patients with P. vivax malaria from the western Brazilian Amazon basin and compared the area under the curve (AUC) with the parasitological outcome at day 28. A total of 19 patients with parasite recurrence within 28 days and 20 patients with no recurrence were included in the study. Chloroquine was measured by high-performance liquid chromatography (HPLC). The pharmacokinetic parameters were estimated by non-compartmental modeling. The maximum concentration ranged from 1285 to 2030 ng/mL. The terminal half-life varied from 5.3 to 12.8 days. The volume of distribution from 1090 to 2340 L/kg, and the area under the curve to the last measurable concentration from 247 to 432 ng/mL.h. The pharmacokinetic parameters were similar in both groups, which suggests the lack of influence of early reappearance of parasites on chloroquine pharmacokinetics.


Assuntos
Antimaláricos , Malária Vivax , Adulto , Antimaláricos/farmacologia , Brasil , Cloroquina/farmacocinética , Cloroquina/uso terapêutico , Resistência a Medicamentos , Humanos , Malária Vivax/induzido quimicamente , Malária Vivax/tratamento farmacológico , Malária Vivax/parasitologia , Plasmodium vivax , Falha de Tratamento
3.
Curr Opin Infect Dis ; 35(5): 404-409, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36066361

RESUMO

PURPOSE OF REVIEW: This is a review of Plasmodium vivax epidemiology, pathogenesis, disease presentation, treatment and innovations in control and elimination. Here, we examine the recent literature and summarize new advances and ongoing challenges in the management of P. vivax . RECENT FINDINGS: P. vivax has a complex life cycle in the human host which impacts disease severity and treatment regimens. There is increasing data for the presence of cryptic reservoirs in the spleen and bone marrow which may contribute to chronic vivax infections and possibly disease severity. Methods to map the geospatial epidemiology of P. vivax chloroquine resistance are advancing, and they will inform local treatment guidelines. P. vivax treatment requires an 8-aminoquinoline to eradicate the dormant liver stage. Evidence suggests that higher doses of 8-aminoquinolines may be needed for radical cure of tropical frequent-relapsing strains. SUMMARY: P. vivax is a significant global health problem. There have been recent developments in understanding the complexity of P. vivax biology and optimization of antimalarial therapy. Studies toward the development of best practices for P. vivax control and elimination programs are ongoing.


Assuntos
Antimaláricos , Malária Vivax , Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Saúde Global , Humanos , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Malária Vivax/prevenção & controle , Plasmodium vivax
4.
J Vector Borne Dis ; 59(2): 154-162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124481

RESUMO

Malaria is one of the major causes of health and disability globally, even after tremendous efforts to eradicate it. Till date no highly effective vaccine is available for its control. The primary reason for the low efficacy of vaccines is extensive polymorphism in potential vaccine candidate antigen genes and HLA polymorphisms in the human population. This problem can be resolved by developing a vaccine using promiscuous peptides to combine the number of HLA alleles. This study predicted T and B cell epitopes (promiscuous peptides) by targeting PPPK-DHPS and DHFR-TS proteins of Plasmodium vivax, using different in silico tools. Selected peptides were characterized as promiscuous peptides on the basis of their immunogenicity, antigenicity and hydrophobicity. Furthermore, to confirm their immunogenicity, these peptides were utilized for molecular modelling and docking analysis. For determining the requisite affinity with distinct HLA Class-I, and HLA Class-II alleles, only five peptides for DHFR-TS and 3 peptides for PPPK-DHPS were chosen as promiscuous peptides. The D1 peptide has the maximum binding energy with HLA alleles, according to HLA-peptide complex modelling and binding interaction analyses. These findings could lead to the development of epitope-based vaccinations with improved safety and efficacy. These epitopes could be major vaccine targets in P. vivax as they possess a higher number of promiscuous peptides. Also, the B cell epitopes possess maximum affinity towards different alleles as analyzed by docking scores. However, further investigation is warranted in vitro and in vivo.


Assuntos
Malária Vivax , Vacinas , Alelos , Epitopos de Linfócito B/genética , Epitopos de Linfócito T/química , Epitopos de Linfócito T/genética , Humanos , Malária Vivax/prevenção & controle , Peptídeos/química , Peptídeos/metabolismo , Plasmodium vivax/genética , Linfócitos T/metabolismo
5.
Front Cell Infect Microbiol ; 12: 986314, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093191

RESUMO

The resilience of Plasmodium vivax, the most widely-distributed malaria-causing parasite in humans, is attributed to its ability to produce dormant liver forms known as hypnozoites, which can activate weeks, months, or even years after an initial mosquito bite. The factors underlying hypnozoite formation and activation are poorly understood, as is the parasite's influence on the host hepatocyte. Here, we shed light on transcriptome-wide signatures of both the parasite and the infected host cell by sequencing over 1,000 P. vivax-infected hepatocytes at single-cell resolution. We distinguish between replicating schizonts and hypnozoites at the transcriptional level, identifying key differences in transcripts encoding for RNA-binding proteins associated with cell fate. In infected hepatocytes, we show that genes associated with energy metabolism and antioxidant stress response are upregulated, and those involved in the host immune response downregulated, suggesting both schizonts and hypnozoites alter the host intracellular environment. The transcriptional markers in schizonts, hypnozoites, and infected hepatocytes revealed here pinpoint potential factors underlying dormancy and can inform therapeutic targets against P. vivax liver-stage infection.


Assuntos
Malária Vivax , Parasitos , Animais , Hepatócitos/parasitologia , Humanos , Malária Vivax/parasitologia , Plasmodium vivax/genética , RNA , Transcriptoma
6.
Front Cell Infect Microbiol ; 12: 916702, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909975

RESUMO

The neglected but highly prevalent Plasmodium vivax in South-east Asia and South America poses a great challenge, with regards to long-term in-vitro culturing and heavily limited functional assays. Such visible challenges as well as narrowed progress in development of experimental research tools hinders development of new drugs and vaccines. The leading vaccine candidate antigen Plasmodium vivax Duffy Binding Protein (PvDBP), is essential for reticulocyte invasion by binding to its cognate receptor, the Duffy Antigen Receptor for Chemokines (DARC), on the host's reticulocyte surface. Despite its highly polymorphic nature, the amino-terminal cysteine-rich region II of PvDBP (PvDBPII) has been considered as an attractive target for vaccine-mediated immunity and has successfully completed the clinical trial Phase 1. Although this molecule is an attractive vaccine candidate against vivax malaria, there is still a question on its viability due to recent findings, suggesting that there are still some aspects which needs to be looked into further. The highly polymorphic nature of PvDBPII and strain-specific immunity due to PvDBPII allelic variation in Bc epitopes may complicate vaccine efficacy. Emergence of various blood-stage antigens, such as PvRBP, PvEBP and supposedly many more might stand in the way of attaining full protection from PvDBPII. As a result, there is an urgent need to assess and re-assess various caveats connected to PvDBP, which might help in designing a long-term promising vaccine for P. vivax malaria. This review mainly deals with a bunch of rising concerns for validation of DBPII as a vaccine candidate antigen for P. vivax malaria.


Assuntos
Malária Vivax , Vacinas , Anticorpos Antiprotozoários , Antígenos de Protozoários , Epitopos , Humanos , Malária Vivax/prevenção & controle , Plasmodium vivax/genética , Domínios Proteicos , Proteínas de Protozoários/metabolismo
7.
PLoS Negl Trop Dis ; 16(8): e0010305, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35921373

RESUMO

BACKGROUND: The simultaneous infection of Plasmodium falciparum and Epstein-Barr virus (EBV) could promote the development of the aggressive endemic Burkitt's Lymphoma (eBL) in children living in P. falciparum holoendemic areas. While it is well-established that eBL is not related to other human malaria parasites, the impact of EBV infection on the generation of human malaria immunity remains largely unexplored. Considering that this highly prevalent herpesvirus establishes a lifelong persistent infection on B-cells with possible influence on malaria immunity, we hypothesized that EBV co-infection could have impact on the naturally acquired antibody responses to P. vivax, the most widespread human malaria parasite. METHODOLOGY/PRINCIPAL FINDINGS: The study design involved three cross-sectional surveys at six-month intervals (baseline, 6 and 12 months) among long-term P. vivax exposed individuals living in the Amazon rainforest. The approach focused on a group of malaria-exposed individuals whose EBV-DNA (amplification of balf-5 gene) was persistently detected in the peripheral blood (PersVDNA, n = 27), and an age-matched malaria-exposed group whose EBV-DNA could never be detected during the follow-up (NegVDNA, n = 29). During the follow-up period, the serological detection of EBV antibodies to lytic/ latent viral antigens showed that IgG antibodies to viral capsid antigen (VCA-p18) were significantly different between groups (PersVDNA > NegVDNA). A panel of blood-stage P. vivax antigens covering a wide range of immunogenicity confirmed that in general PersVDNA group showed low levels of antibodies as compared with NegVDNA. Interestingly, more significant differences were observed to a novel DBPII immunogen, named DEKnull-2, which has been associated with long-term neutralizing antibody response. Differences between groups were less pronounced with blood-stage antigens (such as MSP1-19) whose levels can fluctuate according to malaria transmission. CONCLUSIONS/SIGNIFICANCE: In a proof-of-concept study we provide evidence that a persistent detection of EBV-DNA in peripheral blood of adults in a P. vivax semi-immune population may impact the long-term immune response to major malaria vaccine candidates.


Assuntos
Linfoma de Burkitt , Coinfecção , Infecções por Vírus Epstein-Barr , Malária Falciparum , Malária Vivax , Malária , Adulto , Anticorpos Antiprotozoários , Formação de Anticorpos , Antígenos Virais , Linfoma de Burkitt/complicações , Linfoma de Burkitt/parasitologia , Criança , Coinfecção/complicações , Estudos Transversais , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Humanos , Malária/complicações , Malária Falciparum/parasitologia , Plasmodium vivax
8.
PLoS Negl Trop Dis ; 16(8): e0010633, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35926062

RESUMO

BACKGROUND: Plasmodium vivax sporozoites reside in the salivary glands of a mosquito before infecting a human host and causing malaria. Previous transcriptome-wide studies in populations of these parasite forms were limited in their ability to elucidate cell-to-cell variation, thereby masking cellular states potentially important in understanding malaria transmission outcomes. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we performed transcription profiling on 9,947 P. vivax sporozoites to assess the extent to which they differ at single-cell resolution. We show that sporozoites residing in the mosquito's salivary glands exist in distinct developmental states, as defined by their transcriptomic signatures. Additionally, relative to P. falciparum, P. vivax displays overlapping and unique gene usage patterns, highlighting conserved and species-specific gene programs. Notably, distinguishing P. vivax from P. falciparum were a subset of P. vivax sporozoites expressing genes associated with translational regulation and repression. Finally, our comparison of single-cell transcriptomic data from P. vivax sporozoite and erythrocytic forms reveals gene usage patterns unique to sporozoites. CONCLUSIONS/SIGNIFICANCE: In defining the transcriptomic signatures of individual P. vivax sporozoites, our work provides new insights into the factors driving their developmental trajectory and lays the groundwork for a more comprehensive P. vivax cell atlas.


Assuntos
Anopheles , Malária Falciparum , Malária Vivax , Malária , Animais , Anopheles/genética , Anopheles/parasitologia , Humanos , Malária/parasitologia , Malária Vivax/parasitologia , Plasmodium vivax/genética , Análise de Sequência de RNA , Esporozoítos/genética , Transcriptoma
9.
Mem Inst Oswaldo Cruz ; 117: e220085, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36043597

RESUMO

BACKGROUND: Malaria is a disease that affects many tropical and subtropical countries, including Brazil. The use of tests for malaria detection is one of the fundamental strategies recommended by the World Health Organization for the control and eradication of the disease. The lack of diagnostic tests leads to an increase in transmission and non-reporting cases. OBJECTIVES: This work described an electrochemical immunosensor for detecting Plasmodium vivax lactate dehydrogenase antigen (Ag-PvLDH). METHODS: The device has developed by immobilising egg yolk IgY antibodies (Ab-PvLDH) on a gold electrode surface using cysteamine as linker. The immunosensor fabrication was followed by differential pulse voltammetry, and contact angle measurements were performed to characterise the modified gold electrode surface. FINDINGS: The results for Ag-PvLDH determination exhibit a linear response at 10-50 µg mL-1 concentration range, with a limit of detection of 455 ng mL-1. The excellent selectivity of the device was confirmed. MAIN CONCLUSIONS: The developed immunosensor showed a good performance, therefore, it can be considered an alternative test to detect malaria caused by P. vivax.


Assuntos
Técnicas Biossensoriais , Malária Vivax , Malária , Antígenos de Protozoários , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas , Ouro , Humanos , Imunoensaio/métodos , L-Lactato Desidrogenase , Limite de Detecção , Malária Vivax/diagnóstico , Plasmodium vivax
10.
Rev Soc Bras Med Trop ; 55: e0490, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35946633

RESUMO

BACKGROUND: The atypical chemokine receptor 1 (ACKR1) gene encodes the Duffy blood group antigens in two allelic forms: FY*A (FY*01) and FY*B (FY*02), which define the Fy(a+b-), Fy(a-b+), and Fy(a+b+) phenotypes. FY*BES (FY*02N.01) is a single T to C substitution at nucleotide -67 that prevents the FY*B from being expressed in red blood cells (RBCs). METHODS: We evaluated 250 residents from a Brazilian malarial endemic region (RsMR). All individuals were phenotyped for Fya and Fyb antigens and genotyped for FY*A, FY*B, FY*B SE , and FY*B weak alleles. RESULTS: Among the 250 individuals, 209 (83.6%) reported previous malaria infection, and 41 (16.4%) did not. The Fy(a+b+) phenotype was present in 97/250 (38.8%), while the Fy(a-b-) was present in 7/250 (2.8%). The FY*A/FY*B was found in 130/250 (52%) and the FY*A/FY*A in 45/250 (18%). The c.1-67>TC was present, in homozygosity, in 11/250 (4.4%). Among 34 individuals with the Fy(a+b-) and FYA*/FYB* mutations, 4/34 (11.8%) had homozygosity for the c.1-67T>C. One individual presented the Fy(a+b-), FY*A/FY*B, and c.1-67T>C in homozygosis, whereas the other presented the Fy(a+b-), FY*A/FY*A, and c.1-67T>C in heterozygosis. CONCLUSIONS: We reported a low prevalence of the Fy(a-b-) in persons who had previously been infected with Plasmodium vivax (67.5%). We observed that 102/141 (72.3%) individuals expressing the Fyb antigen had a P. vivax infection, indicating the importance of the Fyb antigen, silenced by a c.1-67T>C mutation in homozygosis, in preventing the P. vivax infection. We showed that the c.1-67T>C mutation in the FY*A did not silence the FY*A expression on RBCs.


Assuntos
Malária Vivax , Malária , Brasil/epidemiologia , Sistema do Grupo Sanguíneo Duffy/genética , Sistema do Grupo Sanguíneo Duffy/metabolismo , Humanos , Malária/genética , Plasmodium vivax , Polimorfismo de Fragmento de Restrição
11.
Sci Rep ; 12(1): 14114, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35982088

RESUMO

Malaria is a serious threat to global health, with over [Formula: see text] of the cases reported in 2020 by the World Health Organization in African countries, including Sudan. Sudan is a low-income country with a limited healthcare system and a substantial burden of malaria. The epidemiology of malaria in Sudan is rapidly changing due to factors including the rapidly developing resistance to drugs and insecticides among the parasites and vectors, respectively; the growing population living in humanitarian settings due to political instability; and the recent emergence of Anopheles stephensi in the country. These factors contribute to changes in the distribution of the parasites species as well as malaria vectors in Sudan, and the shifting patterns of malaria epidemiology underscore the need for investment in improved situational awareness, early preparedness, and a national prevention and control strategy that is updated, evidence based, and proactive. A key component of this strategy is accurate, high-resolution endemicity maps of species-specific malaria. Here, we present a spatiotemporal Bayesian model, developed in collaboration with the Sudanese Ministry of Health, that predicts a fine-scale (1 km [Formula: see text] 1 km) clinical incidence and seasonality profiles for Plasmodium falciparum and Plasmodium vivax across the country. We use monthly malaria case counts for both species collected via routine surveillance between January 2017 and December 2019, as well as a suite of high-resolution environmental covariates to inform our predictions. These epidemiological maps provide a useful resource for strategic planning and cost-effective implementation of malaria interventions, thus informing policymakers in Sudan to achieve success in malaria control and elimination.


Assuntos
Malária Falciparum , Malária Vivax , Malária , Animais , Teorema de Bayes , Humanos , Incidência , Malária/epidemiologia , Malária/prevenção & controle , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Malária Vivax/prevenção & controle , Mosquitos Vetores , Plasmodium vivax
12.
Trends Parasitol ; 38(10): 882-889, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36031553

RESUMO

The ability of the intraerythrocytic Plasmodium spp. to form spontaneous rosettes with uninfected red blood cells (URBCs) has been observed in the medically important malaria parasites. Since the discovery of rosettes in the late 1980s, different formation mechanisms and pathobiological roles have been postulated for rosetting; most of which have focused on Plasmodium falciparum. Recent breakthroughs, including new data from Plasmodium vivax, have highlighted the multifaceted roles of rosetting in the immunopathobiology and the development of drug resistance in human malaria. Here, we provide new perspectives on the formation and the role of rosetting in malaria rheopathobiology.


Assuntos
Malária Falciparum , Malária , Adesão Celular , Eritrócitos/parasitologia , Humanos , Malária Falciparum/parasitologia , Plasmodium falciparum , Plasmodium vivax , Formação de Roseta
13.
Trends Parasitol ; 38(10): 829-830, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36038428

RESUMO

Serological surveillance is a useful tool for revealing hotspots of transmission intensity or cryptic asymptomatic reservoirs, especially as malaria transmission declines. Such approaches can help us to understand malaria epidemiology, but also to guide interventions. Recently, Longley et al. refined a panel for Plasmodium vivax serological surveillance to aid in malaria elimination.


Assuntos
Malária Falciparum , Malária Vivax , Malária , Humanos , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Malária Vivax/prevenção & controle , Plasmodium falciparum , Plasmodium vivax
14.
PLoS One ; 17(8): e0272094, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35925877

RESUMO

BACKGROUND: Malaria elimination effort is hampered not only by the lack of effective medication but also due to the lack of sensitive diagnostic tools to detect infections with low levels of parasitemia. Therefore, more sensitive and specific high-throughput molecular diagnostic approaches are needed for accurate malaria diagnosis. METHODS: In the present study, the performance of a novel single-tube MC004 real-time polymerase chain reaction (PCR) assay (MRC-Holland, Amsterdam, the Netherlands) was assessed for the detection of infection and discrimination of Plasmodium species. Blood samples (n = 150) were collected from malaria suspected patients at Adama malaria diagnosis and treatment centre, Adama, central Ethiopia. The positive predictive value (PPV), negative predictive value (NPV), analytical sensitivity and specificity of the assay were assessed against the conventional microscopic method. RESULTS: Plasmodium species were detected in 59 (39.3%) of the samples by microscopy and in 62 (41.3%) by the novel MC004 RT-PCR. Plasmodium vivax, Plasmodium falciparum and mixed infections with Plasmodium falciparum & Plasmodium vivax accounted for 47.5%, 40.6% and 11.9% respectively as detected by microscopy. The MC004 RT-PCR assay identified 59.7% and 40.3% of the samples positive for Plasmodium vivax and Plasmodium falciparum respectively. The sensitivity, specificity, PPV, and NPV of the MC004 RT-PCR assay were 95.8%, 97.8%, 92%, and 98.9%, respectively. No mixed infections were detected using the MC004 assay. CONCLUSION: The MC004 RT-PCR assay is a useful tool for the early detection of malaria and identification of Plasmodium species with a high degree of sensitivity and specificity. Due to its high sensitivity, and simplicity (being a single-tube assay), the MC004 is suitable for use in clinical settings and epidemiological studies.


Assuntos
Coinfecção , Malária Falciparum , Malária Vivax , Malária , Plasmodium , Humanos , Malária/diagnóstico , Malária Falciparum/diagnóstico , Malária Vivax/diagnóstico , Plasmodium/genética , Plasmodium falciparum/genética , Plasmodium vivax/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade
15.
Malar J ; 21(1): 241, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35987665

RESUMO

BACKGROUND: As Indonesia aims for malaria elimination by 2030, provisional malaria epidemiology and risk factors evaluation are important in pursue of this national goal. Therefore, this study aimed to understand the risk factor of malaria in Northern Sumatera. METHODS: Malaria cases from 2019 to 2020 were obtained from the Indonesian Ministry of Health Electronic Database. Climatic variables were provided by the Center for Meteorology and Geophysics Medan branch office. Multivariable logistic regression was undertaken to understand the risk factors of imported malaria. A zero-inflated Poisson multivariable regression model was used to study the climatic drivers of indigenous malaria. RESULTS: A total of 2208 (indigenous: 76.0% [1679] and imported: 17.8% [392]) were reported during the study period. Risk factors of imported malaria were: ages 19-30 (adjusted odds ratio [AOR] = 3.31; 95% confidence interval [CI] 1.67, 2.56), 31-45 (AOR = 5.69; 95% CI 2.65, 12.20), and > 45 years (AOR = 5.11; 95% CI 2.41, 10.84). Military personnel and forest workers and miners were 1,154 times (AOR = 197.03; 95% CI 145.93, 9,131.56) and 44 times (AOR = 44.16; 95% CI 4.08, 477,93) more likely to be imported cases as compared to those working as employees and traders. Indigenous Plasmodium falciparum increased by 12.1% (95% CrI 5.1%, 20.1%) for 1% increase in relative humidity and by 21.0% (95% CrI 9.0%, 36.2%) for 1 °C increase in maximum temperature. Plasmodium vivax decreased by 0.8% (95% CrI 0.2%, 1.3%) and 16.7% (95% CrI 13.7%, 19.9%) for one meter and 1 °C increase of altitude and minimum temperature. Indigenous hotspot was reported by Kota Tanjung Balai city and Asahan regency, respectively. Imported malaria hotspots were reported in Batu Bara, Kota Tebing Tinggi, Serdang Bedagai and Simalungun. CONCLUSION: Both indigenous and imported malaria is limited to a few regencies and cities in Northern Sumatera. The control measures should focus on these risk factors to achieve elimination in Indonesia.


Assuntos
Malária Falciparum , Malária Vivax , Malária , Adulto , Humanos , Indonésia/epidemiologia , Malária/epidemiologia , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Plasmodium falciparum , Plasmodium vivax , Análise Espacial , Adulto Jovem
16.
Front Cell Infect Microbiol ; 12: 950909, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36017364

RESUMO

A more sensitive surveillance tool is needed to identify Plasmodium vivax infections for treatment and to accelerate malaria elimination efforts. To address this challenge, our laboratory has developed an eight-antigen panel that detects total IgG as serological markers of P. vivax exposure within the prior 9 months. The value of these markers has been established for use in areas with low transmission. In moderate-high transmission areas, there is evidence that total IgG is more long-lived than in areas with low transmission, resulting in poorer performance of these markers in these settings. Antibodies that are shorter-lived may be better markers of recent infection for use in moderate-high transmission areas. Using a multiplex assay, the antibody temporal kinetics of total IgG, IgG1, IgG3, and IgM against 29 P. vivax antigens were measured over 36 weeks following asymptomatic P. vivax infection in Papua New Guinean children (n = 31), from an area with moderate-high transmission intensity. IgG3 declined faster to background than total IgG, IgG1, and IgM. Based on these kinetics, IgG3 performance was then assessed for classifying recent exposure in a cohort of Peruvian individuals (n = 590; age 3-85 years) from an area of moderate transmission intensity. Using antibody responses against individual antigens, the highest performance of IgG3 in classifying recent P. vivax infections in the prior 9 months was to one of the Pv-fam-a proteins assessed (PVX_125728) (AUC = 0.764). Surprisingly, total IgG was overall a better marker of recent P. vivax infection, with the highest individual classification performance to RBP2b1986-2653 (PVX_094255) (AUC = 0.838). To understand the acquisition of IgG3 in this Peruvian cohort, relevant epidemiological factors were explored using a regression model. IgG3 levels were positively associated with increasing age, living in an area with (relatively) higher transmission intensity, and having three or more PCR-detected blood-stage P. vivax infections within the prior 13 months. Overall, we found that IgG3 did not have high accuracy for detecting recent exposure to P. vivax in the Peruvian cohort, with our data suggesting that this is due to the high levels of prior exposure required to acquire high IgG3 antibody levels.


Assuntos
Malária Falciparum , Malária Vivax , Malária , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antiprotozoários , Infecções Assintomáticas , Biomarcadores , Criança , Pré-Escolar , Humanos , Imunoglobulina G , Imunoglobulina M , Malária Vivax/diagnóstico , Pessoa de Meia-Idade , Plasmodium falciparum , Plasmodium vivax , Adulto Jovem
17.
Front Cell Infect Microbiol ; 12: 953187, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034708

RESUMO

Although the power of genetic surveillance tools has been acknowledged widely, there is an urgent need in malaria endemic countries for feasible and cost-effective tools to implement in national malaria control programs (NMCPs) that can generate evidence to guide malaria control and elimination strategies, especially in the case of Plasmodium vivax. Several genetic surveillance applications ('use cases') have been identified to align research, technology development, and public health efforts, requiring different types of molecular markers. Here we present a new highly-multiplexed deep sequencing assay (Pv AmpliSeq). The assay targets the 33-SNP vivaxGEN-geo panel for country-level classification, and a newly designed 42-SNP within-country barcode for analysis of parasite dynamics in Vietnam and 11 putative drug resistance genes in a highly multiplexed NGS protocol with easy workflow, applicable for many different genetic surveillance use cases. The Pv AmpliSeq assay was validated using: 1) isolates from travelers and migrants in Belgium, and 2) routine collections of the national malaria control program at sentinel sites in Vietnam. The assay targets 229 amplicons and achieved a high depth of coverage (mean 595.7 ± 481) and high accuracy (mean error-rate of 0.013 ± 0.007). P. vivax parasites could be characterized from dried blood spots with a minimum of 5 parasites/µL and 10% of minority-clones. The assay achieved good spatial specificity for between-country prediction of origin using the 33-SNP vivaxGEN-geo panel that targets rare alleles specific for certain countries and regions. A high resolution for within-country diversity in Vietnam was achieved using the designed 42-SNP within-country barcode that targets common alleles (median MAF 0.34, range 0.01-0.49. Many variants were detected in (putative) drug resistance genes, with different predominant haplotypes in the pvmdr1 and pvcrt genes in different provinces in Vietnam. The capacity of the assay for high resolution identity-by-descent (IBD) analysis was demonstrated and identified a high rate of shared ancestry within Gia Lai Province in the Central Highlands of Vietnam, as well as between the coastal province of Binh Thuan and Lam Dong. Our approach performed well in geographically differentiating isolates at multiple spatial scales, detecting variants in putative resistance genes, and can be easily adjusted to suit the needs in other settings in a country or region. We prioritize making this tool available to researchers and NMCPs in endemic countries to increase ownership and ensure data usage for decision-making and malaria policy.


Assuntos
Antimaláricos , Malária Vivax , Malária , Resistência a Medicamentos , Humanos , Plasmodium vivax
18.
Virulence ; 13(1): 634-653, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36036460

RESUMO

Globally, malaria is a public health concern, with severe malaria (SM) contributing a major share of the disease burden in malaria endemic countries. In this context, identification and validation of SM biomarkers are essential in clinical practice. Some biomarkers (C-reactive protein, angiopoietin 2, angiopoietin-2/1 ratio, platelet count, histidine-rich protein 2) have yielded interesting results in the prognosis of Plasmodium falciparum severe malaria, but for severe P. vivax and P. knowlesi malaria, similar evidence is missing. The validation of these biomarkers is hindered by several factors such as low sample size, paucity of evidence-evaluating studies, suboptimal values of sensitivity/specificity, poor clinical practicality of measurement methods, mixed Plasmodium infections, and good clinical value of the biomarkers for concurrent infections (pneumonia and current COVID-19 pandemic). Most of these biomarkers are non-specific to pathogens as they are related to host response and hence should be regarded as prognostic/predictive biomarkers that complement but do not replace pathogen biomarkers for clinical evaluation of SM patients. This review highlights the importance of research on diagnostic/predictive/therapeutic biomarkers, neglected malaria species, and clinical practicality of measurement methods in future studies. Finally, the importance of omics technologies for faster identification/validation of SM biomarkers is also included.


Assuntos
COVID-19 , Malária Falciparum , Malária , Biomarcadores , Humanos , Pandemias , Plasmodium falciparum , Plasmodium vivax
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