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1.
Mem Inst Oswaldo Cruz ; 116: e200513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33566952

RESUMO

BACKGROUND: Different strategies for improvement of malaria control and elimination are based on the blockage of malaria parasite transmission to the mosquito vector. These strategies include the drugs that target the plasmodial sexual stages in humans and the early developmental stages inside mosquitoes. OBJECTIVES: Here we tested Malaria Box compounds in order to evaluate their activity against male and female gametocytes in Plasmodium berghei, mosquito infection in P. vivax and ookinete formation in both species. METHODS/FINDINGS: The membrane feeding assay and the development of ookinetes by a 24 h ex vivo culture and the ookinete yield per 1000 erythrocytes were used to test transmission-blocking potential of the Malaria Box compounds in P. vivax. For P. berghei we used flow cytometry to evaluate male and female gametocyte time course and fluorescence microscopy to check the ookinete development. The two species used in this study showed similar results concerning the compounds' activity against gametocytes and ookinetes, which were different from those in P. falciparum. In addition, from the eight Malaria Box compounds tested in both species, compounds MMV665830, MMV665878 and MMV665941 were selected as a hit compounds due the high inhibition observed. CONCLUSION: Our results showed that P. berghei is suitable as an initial screening system to test compounds against P. vivax.


Assuntos
Malária Vivax/prevenção & controle , Mosquitos Vetores/parasitologia , Plasmodium berghei/efeitos dos fármacos , Plasmodium vivax/efeitos dos fármacos , Animais , Malária Vivax/tratamento farmacológico , Malária Vivax/transmissão
2.
BMC Infect Dis ; 21(1): 91, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478414

RESUMO

BACKGROUND: Informed decision making is underlined by all tiers in the health system. Poor data record system coupled with under- (over)-reporting of malaria cases affects the country's malaria elimination activities. Thus, malaria data at health facilities and health offices are important particularly to monitor and evaluate the elimination progresses. This study was intended to assess overall reported malaria cases, reporting quality, spatiotemporal trends and factors associated in Gedeo zone, South Ethiopia. METHODS: Past 8 years retrospective data stored in 17 health centers and 5 district health offices in Gedeo Zone, South Ethiopia were extracted. Malaria cases data at each health center with sociodemographic information, between January 2012 and December 2019, were included. Meteorological data were obtained from the national meteorology agency of Ethiopia. The data were analyzed using Stata 13. RESULTS: A total of 485,414 suspected cases were examined for malaria during the previous 8 years at health centers. Of these suspects, 57,228 (11.79%) were confirmed malaria cases with an overall decline during the 8-year period. We noted that 3758 suspected cases and 467 confirmed malaria cases were not captured at the health offices. Based on the health centers records, the proportions of Plasmodium falciparum (49.74%) and P. vivax (47.59%) infection were nearly equivalent (p = 0.795). The former was higher at low altitudes while the latter was higher at higher altitudes. The over 15 years of age group accounted for 11.47% of confirmed malaria cases (p < 0.001). There was high spatiotemporal variation: the highest case record was during Belg (12.52%) and in Dilla town (18,150, 13.17%, p < 0.001) which is located at low altitude. Monthly rainfall and minimum temperature exhibited strong associations with confirmed malaria cases. CONCLUSION: A notable overall decline in malaria cases was observed during the eight-year period. Both P. falciparum and P. vivax were found at equivalent endemicity level; hence control measures should continue targeting both species. The noticed under reporting, the high malaria burden in urban settings, low altitudes and Belg season need spatiotemporal consideration by the elimination program.


Assuntos
Malária/epidemiologia , Altitude , Demografia , Notificação de Doenças/normas , Notificação de Doenças/estatística & dados numéricos , Etiópia/epidemiologia , Feminino , Humanos , Malária/diagnóstico , Malária/parasitologia , Malária/prevenção & controle , Masculino , Meteorologia , Análise Multivariada , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/isolamento & purificação , Prevalência , Estudos Retrospectivos , Estações do Ano
3.
Drug Discov Ther ; 14(6): 330-335, 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33390562

RESUMO

Traditionally attributed only to Plasmodium falciparum, Plasmodium vivax has recently been reported to cause a significant burden of complicated malaria cases. The present study aimed to delineate the clinical spectrum and identify predictors for severe disease. This was a prospective observational cohort study conducted at a tertiary care hospital in North India. Patients with acute febrile illness (AFI) aged at least 14 years were included if they were diagnosed with vivax malaria based on rapid kits or peripheral smears. Clinical data and investigations during hospital stay was recorded. 439 cases of acute febrile illness were screened, of whom 50 (11%) were diagnosed with malaria including eight P. falciparum infections. Forty-two vivax malaria cases, 22 (52%) of whom were severe, were followed till discharge or death. The median age of the cohort was 24.5 years (Q1-Q3, 19-36 years), including a total of 29 males (69%). Severe malaria was more frequently associated with historical complaints of oliguria or dyspnea, and examination findings of pallor, splenomegaly or altered sensorium. The following five factors were identified to predict severe disease: prolonged illness over 7 days, symptoms of oliguria or dyspnea, examination findings of pallor or crepitations on auscultation. Malaria accounts for 1 in 10 cases of AFI at our North Indian tertiary care center and approximately half of them present with severe disease. Prolonged duration of disease prior to presentation is a modifiable predictor for severe disease and should be targeted for reducing morbidity.


Assuntos
Febre/parasitologia , Hospitalização/estatística & dados numéricos , Malária Vivax/epidemiologia , Plasmodium vivax/patogenicidade , Adulto , Dispneia/epidemiologia , Dispneia/etiologia , Feminino , Humanos , Índia , Tempo de Internação , Masculino , Oligúria/epidemiologia , Oligúria/etiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Centros de Atenção Terciária , Adulto Jovem
4.
Exp Parasitol ; 222: 108064, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33421382

RESUMO

Experimental studies for understanding the relationship between Plasmodium vivax and its vector hosts are difficult, because of to the lack of a long-term, in vitro continuous culture system unavailability of infected blood samples, seasonality of the disease, and the concentration of most cases in remote areas. This study evaluates the duration of the infectivity of P. vivax to Anopheles aquasalis after collecting blood from malaria-infected patients. Blood was collected from patients and stored at 4 °C and 37 °C. Every day, for 4 days, the blood was fed to An. aquasalis adult females, and a Giemsa-stained thick blood smear was mounted to account for sexual (gametocytes) and asexual (trophozoites and schizonts) stages and calculate parasitemia. Oocysts in the midgut of the mosquitoes were counted on the seventh day after feeding. Kruskal-Wallis test was used to compare the mean number of oocysts (MO) and the parasite density (PD) in each storage condition and post-infection time-points. The Mann-Whitney test was used to compare the number of oocysts for each day between temperatures. The results show that P. vivax stored at 4 °C and at 37 °C has its infectivity to An. aquasalis preserved for 2 days and 3 days, respectively. Infection rate (IR), PD and MO were higher on the day of blood collection and decreased gradually over time. The parasite density (number of parasites/µL) diminished faster at 4 °C than at 37 °C. In this study, a preservation protocol is shown for long-lasting infectivity of P. vivax in a blood sample taken from malaria-infected patients. These results show that infectivity of P. vivax stored at 4 °C and at 37 °C to An. aquasalis persist until 3 days after blood collection, but parasite density, infection rate, and mean of oocysts decreased 24h after blood collection. Since the malaria cases are increasingly far from the urban areas these results indicate that is possible, losing some infectivity, to realize experimental infections several dozen hours after the blood collection. However, it is necessary to improve the procedures for preserving P. vivax gametocytes for mosquito infection in the laboratory.


Assuntos
Anopheles/parasitologia , Malária Vivax/parasitologia , Mosquitos Vetores/parasitologia , Plasmodium vivax/fisiologia , Adulto , Idoso , Animais , Brasil , Feminino , Humanos , Malária Vivax/sangue , Malária Vivax/transmissão , Masculino , Pessoa de Meia-Idade , Plasmodium vivax/patogenicidade , População Rural , Temperatura , Fatores de Tempo , Adulto Jovem
5.
Anal Chem ; 93(3): 1416-1422, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33369387

RESUMO

We demonstrate for the first time a fast aptamer generation method based on the screen-printed electrodynamic microfluidic channel device, where a specific aptamer selectively binds to a target protein on channel walls, following recovery and separation. A malaria protein as a model target, Plasmodium vivax lactate dehydrogenase (PvLDH) was covalently bonded to the conductive polymer layer formed on the carbon channel walls to react with the DNA library in a fluid. Then, the AC electric field was symmetrically applied on the channel walls for inducing the specific binding of the target protein to DNA library molecules. In this case, the partitioning efficiency between PvLDH and DNA library in the channel was attained to be 1.67 × 107 with the background of 5.56 × 10-6, which was confirmed using the quantitative polymerase chain reaction (qPCR). The selectively captured DNAs were isolated from the protein and separated in situ to give five aptamers with different sequences by one round cycle. The dissociation constants (Kd) of the selected aptamers were determined employing both electrochemical impedance spectroscopy (EIS) and the fluorescence method. The sensing performance of each aptamer was evaluated for the PvLDH detection after individual immobilization on the screen-printed array electrodes. The most sensitive aptamer revealed a detection limit of 7.8 ± 0.4 fM. The sensor reliability was evaluated by comparing it with other malaria sensors.


Assuntos
Aptâmeros de Nucleotídeos/química , L-Lactato Desidrogenase/análise , Técnicas Analíticas Microfluídicas , Plasmodium vivax/enzimologia , Aptâmeros de Nucleotídeos/síntese química , Espectroscopia Dielétrica , Fluorescência , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo
6.
PLoS Negl Trop Dis ; 14(12): e0008962, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33315861

RESUMO

Malaria incidence in Panama has plateaued in recent years in spite of elimination efforts, with almost all cases caused by Plasmodium vivax. Notwithstanding, overall malaria prevalence remains low (fewer than 1 case per 1000 persons). We used selective whole genome amplification to sequence 59 P. vivax samples from Panama. The P. vivax samples were collected from two periods (2007-2009 and 2017-2019) to study the population structure and transmission dynamics of the parasite. Imported cases resulting from increased levels of human migration could threaten malaria elimination prospects, and four of the samples evaluated came from individuals with travel history. We explored patterns of recent common ancestry among the samples and observed that a highly genetically related lineage (termed CL1) was dominant among the samples (47 out of 59 samples with good sequencing coverage), spanning the entire period of the collection (2007-2019) and all regions of the country. We also found a second, smaller clonal lineage (termed CL2) of four parasites collected between 2017 and 2019. To explore the regional context of Panamanian P. vivax we conducted principal components analysis and constructed a neighbor-joining tree using these samples and samples collected worldwide from a previous study. Three of the four samples with travel history clustered with samples collected from their suspected country of origin (consistent with importation), while one appears to have been a result of local transmission. The small number of Panamanian P. vivax samples not belonging to either CL1 or CL2 clustered with samples collected from Colombia, suggesting they represent the genetically similar ancestral P. vivax population in Panama or were recently imported from Colombia. The low diversity we observe in Panama indicates that this parasite population has been previously subject to a severe bottleneck and may be eligible for elimination. Additionally, while we confirmed that P. vivax is imported to Panama from diverse geographic locations, the lack of impact from imported cases on the overall parasite population genomic profile suggests that onward transmission from such cases is limited and that imported cases may not presently pose a major barrier to elimination.


Assuntos
Erradicação de Doenças , Genética Populacional , Malária Vivax/parasitologia , Plasmodium vivax/genética , Viagem , Animais , Anopheles , Colômbia/epidemiologia , Feminino , Humanos , Incidência , Malária Vivax/prevenção & controle , Metagenômica , Panamá/epidemiologia , Plasmodium vivax/isolamento & purificação
7.
PLoS Negl Trop Dis ; 14(12): e0008945, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33326439

RESUMO

BACKGROUND: Plasmodium vivax has been recently discovered as a significant cause of malaria in Mauritania, although very rare elsewhere in West Africa. It has not been known if this is a recently introduced or locally remnant parasite population, nor whether the genetic structure reflects epidemic or endemic transmission. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the P. vivax population genetic structure in Mauritania and compare with populations previously analysed elsewhere, multi-locus genotyping was undertaken on 100 clinical isolates, using a genome-wide panel of 38 single nucleotide polymorphisms (SNPs), plus seven SNPs in drug resistance genes. The Mauritanian P. vivax population is shown to be genetically diverse and divergent from populations elsewhere, indicated consistently by genetic distance matrix analysis, principal components analyses, and fixation indices. Only one isolate had a genotype clearly indicating recent importation, from a southeast Asian source. There was no linkage disequilibrium in the local parasite population, and only a small number of infections appeared to be closely genetically related, indicating that there is ongoing genetic recombination consistent with endemic transmission. The P. vivax diversity in a remote mining town was similar to that in the capital Nouakchott, with no indication of local substructure or of epidemic population structure. Drug resistance alleles were virtually absent in Mauritania, in contrast with P. vivax in other areas of the world. CONCLUSIONS/SIGNIFICANCE: The molecular epidemiology indicates that there is long-standing endemic transmission that will be very challenging to eliminate. The virtual absence of drug resistance alleles suggests that most infections have been untreated, and that this endemic infection has been more neglected in comparison to P. vivax elsewhere.


Assuntos
Resistência a Medicamentos/genética , Variação Genética , Genética Populacional , Malária Vivax/parasitologia , Plasmodium vivax/genética , Alelos , Genótipo , Técnicas de Genotipagem , Humanos , Desequilíbrio de Ligação , Mauritânia/epidemiologia , Tipagem de Sequências Multilocus , Plasmodium vivax/isolamento & purificação , Polimorfismo de Nucleotídeo Único
9.
BMC Infect Dis ; 20(1): 671, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933490

RESUMO

BACKGROUND: The increasing antimalarial drug resistance is a significant hindrance to malaria control and elimination programs. For the last six decades, chloroquine (CQ) plus pyrimethamine remains the first-line treatment for P. vivax malaria. Regions where both P. falciparum and P. vivax co-exist, P. vivax is exposed to antifolate drugs due to either misdiagnosis or improper treatment that causes selective drug pressure to evolve. Therefore, the present study aims to estimate antimalarial drug resistance among the complicated and uncomplicated P. vivax patients. METHODS: A total of 143 P. vivax malaria positive patients were enrolled in this study, and DNA was isolated from their blood samples. Pvcrt-o, Pvmdr-1, Pvdhps, and Pvdhfr genes were PCRs amplified, and drug resistance-associated gene mutations were analyzed. Statistical analysis of the drug resistance genes and population diversity was performed using MEGA vs. 7.0.21 and DnaSP v software. RESULTS: Among the CQ resistance marker gene Pvcrt-o, the prevalence of K10 insertion was 17.5% (7/40) and 9.5% (7/73) of complicated and uncomplicated P vivax group isolates respectively. In Pvmdr-1, double mutant haplotype (M958/L1076) was found in 99% of the clinical isolates. Among the pyrimethamine resistance-associated gene Pvdhfr, the double mutant haplotype I13P33F57R58T61N117I173 was detected in 23% (11/48) in complicated and 20% (17/85) in uncomplicated group isolates. In the sulphadoxine resistance-associated Pvdhps gene, limited polymorphism was observed with the presence of a single mutant (D459A) among 16 and 5% of the clinical isolates in the complicated and uncomplicated group respectively. CONCLUSION: The study presents the situations of polymorphism in the antimalarial drug resistance-associated genes and emphasizes the need for regular surveillance. It is imperative for the development of suitable antimalarial drug policy in India.


Assuntos
Antimaláricos/uso terapêutico , Resistência a Medicamentos/genética , Malária Vivax/tratamento farmacológico , Plasmodium vivax/genética , Proteínas de Protozoários/genética , Adolescente , Criança , Pré-Escolar , Cloroquina/uso terapêutico , DNA de Protozoário/genética , DNA de Protozoário/metabolismo , Feminino , Antagonistas do Ácido Fólico/uso terapêutico , Haplótipos , Humanos , Índia , Masculino , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Plasmodium vivax/isolamento & purificação , Polimorfismo de Nucleotídeo Único , Adulto Jovem
10.
Am J Trop Med Hyg ; 103(4): 1549-1552, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32748776

RESUMO

Plasmodium vivax is co-endemic with Plasmodium falciparum in Peru, and optimum management requires distinguishing these two species in the blood of patients. For the differential identification of P. vivax and other Plasmodium spp., the LoopampTM Malaria Pan Detection Kit in combination with the Loopamp Malaria Pv Detection Kit (Eiken Chemical Co. Ltd., Tokyo, Japan) was used to evaluate 559 whole blood samples collected in 2017 from febrile patients with suspected malaria attending different health facilities in the Loreto region. The Loopamp Malaria Pan Detection Kit showed a sensitivity of 87.7% (95% CI: 83.5-91.9) and a specificity of 94.4% (95% CI: 91.9-96.9) and good agreement with PCR (Cohen's kappa 0.8266, 95% CI: 0.7792-0.874). By comparison, the Loopamp Malaria Pv Detection Kit showed a similar sensitivity (84.4%, 95% CI: 79.0-89.7) and specificity (92.4%, 95% CI: 89.7-95.0) and substantial agreement with PCR (Cohen's kappa: 0.7661, 95% CI: 0.7088-0.8234).


Assuntos
Malária Vivax/diagnóstico , Malária/diagnóstico , Plasmodium vivax/isolamento & purificação , Plasmodium/isolamento & purificação , Febre , Humanos , Malária/parasitologia , Malária Vivax/parasitologia , Técnicas de Amplificação de Ácido Nucleico , Peru , Plasmodium/genética , Plasmodium vivax/genética , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade
11.
Am J Trop Med Hyg ; 103(4): 1540-1548, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32748781

RESUMO

Malaria in Vietnam has become focal to a few provinces, including Phu Yen. This study aimed to assess correlations between intervention (population proportion protected by insecticide-treated nets and indoor residual spraying) and climatic variables with malaria incidence in Phu Yen Province. The Vietnam National Institute of Malariology, Parasitology, and Entomology provided incidence data for Plasmodium falciparum and Plasmodium vivax for 104 communes of Phu Yen Province from January 2005 to December 2016. A multivariable, zero-inflated Poisson regression model was developed with a conditional autoregressive prior structure to identify the underlying spatial structure of the data and quantify associations with covariates. There were a total of 2,778 P. falciparum and 1,770 P. vivax cases during the study period. Plasmodium falciparum and P. vivax incidence increased by 5.4% (95% credible interval [CrI] 5.1%, 5.7%) and 3.2% (95% CrI 2.9%, 3.5%) for a 10-mm increase in precipitation without lag, respectively. Plasmodium falciparum and P. vivax incidence decreased by 7.7% (95% CrI 5.6%, 9.7%) and 10.5% (95% CrI 8.3%, 12.6%) for a 1°C increase in minimum temperature without lag, respectively. There was a > 95% probability of a higher than provincial average trend of P. falciparum and P. vivax in Song Cau and Song Hoa districts. There was a > 95% probability of a lower than provincial average trend in Tuy Dong Xuan and Hoa districts for both species. Targeted distribution of resources, including intensified interventions, in this part of the province will be required for local malaria elimination.


Assuntos
Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Plasmodium falciparum/fisiologia , Plasmodium vivax/fisiologia , Monitoramento Epidemiológico , Geografia , Humanos , Incidência , Malária Falciparum/parasitologia , Malária Vivax/parasitologia , Risco , Análise Espaço-Temporal , Temperatura , Vietnã/epidemiologia
12.
PLoS Negl Trop Dis ; 14(7): e0008526, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32735631

RESUMO

Each year, 4.3 million pregnant women are exposed to malaria risk in Latin America and the Caribbean. Plasmodium vivax causes 76% of the regional malaria burden and appears to be less affected than P. falciparum by current elimination efforts. This is in part due to the parasite's ability to stay dormant in the liver and originate relapses within months after a single mosquito inoculation. Primaquine (PQ) is routinely combined with chloroquine (CQ) or other schizontocidal drugs to supress P. vivax relapses and reduce the risk of late blood-stage recrudescences of parasites with low-grade CQ resistance. However, PQ is contraindicated for pregnant women, who remain at increased risk of repeated infections following CQ-only treatment. Here we apply a mathematical model to time-to-recurrence data from Juruá Valley, Brazil's main malaria transmission hotspot, to quantify the extra burden of parasite recurrences attributable to PQ ineligibility in pregnant women. The model accounts for competing risks, since relapses and late recrudescences (that may be at least partially prevented by PQ) and new infections (that are not affected by PQ use) all contribute to recurrences. We compare recurrence rates observed after primary P. vivax infections in 158 pregnant women treated with CQ only and 316 P. vivax infections in non-pregnant control women, matched for age, date of infection, and place of residence, who were administered a standard CQ-PQ combination. We estimate that, once infected with P. vivax, 23% of the pregnant women have one or more vivax malaria recurrences over the next 12 weeks; 86% of these early P. vivax recurrences are attributable to relapses or late recrudescences, rather than new infections that could be prevented by reducing malaria exposure during pregnancy. Model simulations indicate that weekly CQ chemoprophylaxis extending over 4 to 12 weeks, starting after the first vivax malaria episode diagnosed in pregnancy, might reduce the risk of P. vivax recurrences over the next 12 months by 20% to 65%. We conclude that post-treatment CQ prophylaxis could be further explored as a measure to prevent vivax malaria recurrences in pregnancy and avert their adverse effects on maternal and neonatal health.


Assuntos
Antimaláricos/uso terapêutico , Malária Vivax/prevenção & controle , Plasmodium vivax , Complicações Parasitárias na Gravidez/prevenção & controle , Primaquina/administração & dosagem , Adolescente , Adulto , Brasil , Estudos de Casos e Controles , Criança , Cloroquina/administração & dosagem , Cloroquina/uso terapêutico , Feminino , Humanos , Malária Vivax/tratamento farmacológico , Modelos Biológicos , Gravidez , Primaquina/uso terapêutico , Recidiva , Adulto Jovem
13.
PLoS Negl Trop Dis ; 14(8): e0008506, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32745103

RESUMO

Plasmodium vivax has become the predominant malaria parasite and a major challenge for malaria elimination in the Greater Mekong Subregion (GMS). Yet, our knowledge about the evolution of P. vivax populations in the GMS is fragmental. We performed whole genome sequencing on 23 P. vivax samples from the China-Myanmar border (CMB) and used 21 high-coverage samples to compare to over 200 samples from the rest of the GMS. Using genome-wide single nucleotide polymorphisms (SNPs), we analyzed population differentiation, genetic structure, migration and potential selection using an array of methods. The CMB parasites displayed a higher proportion of monoclonal infections, and 52% shared over 90% of their genomes in identity-by-descent segments with at least one other sample from the CMB, suggesting preferential expansion of certain parasite strains in this region, likely resulting from the P. vivax outbreaks occurring during this study period. Principal component, admixture, fixation index and phylogenetic analyses all identified that parasites from the CMB were genetically distinct from parasites from eastern parts of the GMS (Cambodia, Laos, Vietnam, and Thailand), whereas the eastern GMS parasite populations were largely undifferentiated. Such a genetic differentiation pattern of the P. vivax populations from the GMS parasite was largely explainable through geographic distance. Using the genome-wide SNPs, we narrowed down to a set of 36 SNPs for differentiating parasites from different areas of the GMS. Genome-wide scans to determine selection in the genome with two statistical methods identified genes potentially under drug selection, including genes associated with antifolate resistance and genes linked to chloroquine resistance in Plasmodium falciparum.


Assuntos
Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Plasmodium vivax/genética , Polimorfismo de Nucleotídeo Único , Antimaláricos/farmacologia , China , Surtos de Doenças , Resistência a Medicamentos/genética , Antagonistas do Ácido Fólico/farmacologia , Genômica , Humanos , Mianmar , Filogenia , Plasmodium vivax/efeitos dos fármacos
14.
BMC Infect Dis ; 20(1): 573, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758164

RESUMO

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


Assuntos
Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Plasmodium falciparum/imunologia , Plasmodium vivax/imunologia , Complicações Parasitárias na Gravidez/epidemiologia , Adolescente , Adulto , Antígenos de Protozoários/sangue , Infecções Assintomáticas , Estudos Transversais , Testes Diagnósticos de Rotina/métodos , Etiópia/epidemiologia , Feminino , Seguimentos , Humanos , Mosquiteiros Tratados com Inseticida , Modelos Logísticos , Malária Falciparum/prevenção & controle , Malária Vivax/prevenção & controle , Razão de Chances , Gravidez , Complicações Parasitárias na Gravidez/prevenção & controle , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
15.
Am J Trop Med Hyg ; 103(5): 1910-1917, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32815508

RESUMO

Liver transaminase elevations after treatment in malaria volunteer infection studies (VISs) have raised safety concerns. We investigated transaminase elevations from two human Plasmodium vivax VISs where subjects were treated with chloroquine (n = 24) or artefenomel (n = 8) and compared them with studies in Thailand (n = 41) and Malaysia (n = 76). In the VISs, alanine transaminase (ALT) increased to ≥ 2.5 × upper limit of normal (ULN) in 11/32 (34%) volunteers, peaking 5-8 days post-treatment. Transaminase elevations were asymptomatic, were not associated with elevated bilirubin, and resolved by day 42. The risk of an ALT ≥ 2.5 × ULN increased more than 4-fold (odds ratio [OR] 4.28; 95% CI: 1.26-14.59; P = 0.02) for every log10 increase in the parasite clearance burden (PCB), defined as the log-fold reduction in parasitemia 24 hours post-treatment. Although an elevated ALT ≥ 2.5 × ULN was more common after artefenomel than after chloroquine (5/8 [63%] versus 6/24 [25%]; OR 5.0; 95% CI: 0.91-27.47; P = 0.06), this risk disappeared when corrected for PCB. Peak ALT also correlated with peak C-reactive protein (R = 0.44; P = 0.012). Elevations in ALT (≥ 2.5 × ULN) were less common in malaria-endemic settings, occurring in 1/41 (2.5%) Thai patients treated with artefenomel, and in none of 76 Malaysians treated with chloroquine or artemisinin combination therapy. Post-treatment transaminase elevations are common in experimental P. vivax infection but do not appear to impact on participant safety. Although the mechanism of these changes remains uncertain, host inflammatory response to parasite clearance may be contributory.


Assuntos
Adamantano/análogos & derivados , Alanina Transaminase/sangue , Antimaláricos/uso terapêutico , Hepatopatias/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Peróxidos/uso terapêutico , Plasmodium vivax/isolamento & purificação , Adamantano/uso terapêutico , Adulto , Artemisininas/uso terapêutico , Cloroquina/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Hepatopatias/sangue , Hepatopatias/parasitologia , Testes de Função Hepática , Malária Vivax/sangue , Malária Vivax/parasitologia , Malásia , Masculino , Parasitemia/tratamento farmacológico , Tailândia , Adulto Jovem
16.
Mikrobiyol Bul ; 54(2): 306-317, 2020 Apr.
Artigo em Turco | MEDLINE | ID: mdl-32723285

RESUMO

Malaria is a life-threatening parasitic disease caused by the parasites belonging to Plasmodium genus. Microscopic examination of Giemsa stained blood smears is accepted as the gold standard diagnostic method. It is recommended to use more than one method in order to strengthen the laboratory diagnosis of malaria which is an important health problem in our country as in the whole world. In this study, it was aimed to compare the results of three different molecular methods and determine which molecular method could be used in the diagnostic algorithm to be applied. DNA was extracted from 280 whole blood sample stored in EDTA tubes using a commercial kit. Three different polymerase chain reaction (PCR) methods were used for the detection of Plasmodium spp. in DNA samples obtained and the results were compared. First, multiplex nested PCR was applied and then in-house real-time PCR (Rt-PCR) which was validated in our laboratory and a commercial Rt-PCR kit were applied. Multiplex nested PCR was accepted as the gold standard and 182 samples that were evaluated as Plasmodium spp. positive and 98 samples that were evaluated as negative were also studied by in-house and commercial Rt-PCR methods. In multiplex nested PCR's first step reaction 1670 base pairs (bp) band was observed in Plasmodium spp. positive samples and 117 bp band was observed in Plasmodium vivax positive samples in the second step reaction. Tm values of P.vivax positive samples were determined as 78-79 in the melting analysis of the in-house Rt-PCR. CT values of the positive samples in in-house Rt-PCR were between 20.03-31.71 and were between 17.26-34.94 in the commercial Rt-PCR. With the in-house Rt-PCR method 180 cases were determined as positive, while with the commercial Rt-PCR method 178 cases were determined as positive. Two samples with the in-house Rt-PCR and 4 samples with the commercial Rt-PCR were considered as false negative. When the sensitivity and specificity of the both methods were calculated, the sensitivity of the in-house Rt-PCR method was 0.98, the specificity was 0.97, the positive predictive value (PPV) was 98%, the negative predictive value (NPV) was 97%, the sensitivity of the commercial Rt-PCR was 0.97, the specificity was 0.95, the PPV was 97%, the NPV was 95%. A high level of agreement (κ: 0.953) was determined between the in-house and the commercial Rt-PCR methods. In order for a test to be accepted as a confirmatory test, its specificity must be high. It was decided that sensitivity and specificity of the in-house Rt-PCR were suitable for using this method in the laboratory diagnosis of Plasmodium species.


Assuntos
Malária , Reação em Cadeia da Polimerase Multiplex , Plasmodium , Reação em Cadeia da Polimerase em Tempo Real , DNA de Protozoário/genética , Humanos , Malária/sangue , Malária/diagnóstico , Malária/parasitologia , Reação em Cadeia da Polimerase Multiplex/normas , Plasmodium/classificação , Plasmodium/genética , Plasmodium falciparum/genética , Plasmodium vivax/genética , Reação em Cadeia da Polimerase em Tempo Real/normas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Proc Natl Acad Sci U S A ; 117(29): 16790-16798, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32631977

RESUMO

Nucleic acid aptamers selected through systematic evolution of ligands by exponential enrichment (SELEX) fold into exquisite globular structures in complex with protein targets with diverse translational applications. Varying the chemistry of nucleotides allows evolution of nonnatural nucleic acids, but the extent to which exotic chemistries can be integrated into a SELEX selection to evolve nonnatural macromolecular binding interfaces is unclear. Here, we report the identification of a cubane-modified aptamer (cubamer) against the malaria biomarker Plasmodium vivax lactate dehydrogenase (PvLDH). The crystal structure of the complex reveals an unprecedented binding mechanism involving a multicubane cluster within a hydrophobic pocket. The binding interaction is further stabilized through hydrogen bonding via cubyl hydrogens, previously unobserved in macromolecular binding interfaces. This binding mechanism allows discriminatory recognition of P. vivax over Plasmodium falciparum lactate dehydrogenase, thereby distinguishing these highly conserved malaria biomarkers for diagnostic applications. Together, our data demonstrate that SELEX can be used to evolve exotic nucleic acids bearing chemical functional groups which enable remarkable binding mechanisms which have never been observed in biology. Extending to other exotic chemistries will open a myriad of possibilities for functional nucleic acids.


Assuntos
Aptâmeros de Nucleotídeos/química , L-Lactato Desidrogenase/química , Malária/diagnóstico , Proteínas de Protozoários/química , Biomarcadores/sangue , Biomarcadores/química , Humanos , Ligação de Hidrogênio , L-Lactato Desidrogenase/sangue , Malária/sangue , Técnicas de Diagnóstico Molecular/métodos , Simulação de Dinâmica Molecular , Plasmodium vivax/enzimologia , Ligação Proteica
18.
PLoS Negl Trop Dis ; 14(7): e0008202, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32645098

RESUMO

Plasmodium vivax is the most widespread and difficult to treat cause of human malaria. The development of vaccines against the blood stages of P. vivax remains a key objective for the control and elimination of vivax malaria. Erythrocyte binding-like (EBL) protein family members such as Duffy binding protein (PvDBP) are of critical importance to erythrocyte invasion and have been the major target for vivax malaria vaccine development. In this study, we focus on another member of EBL protein family, P. vivax erythrocyte binding protein (PvEBP). PvEBP was first identified in Cambodian (C127) field isolates and has subsequently been showed its preferences for binding reticulocytes which is directly inhibited by antibodies. We analysed PvEBP sequence from 316 vivax clinical isolates from eight countries including China (n = 4), Ethiopia (n = 24), Malaysia (n = 53), Myanmar (n = 10), Papua New Guinea (n = 16), Republic of Korea (n = 10), Thailand (n = 174), and Vietnam (n = 25). PvEBP gene exhibited four different phenotypic clusters based on the insertion/deletion (indels) variation. PvEBP-RII (179-479 aa.) showed highest polymorphism similar to other EBL family proteins in various Plasmodium species. Whereas even though PvEBP-RIII-V (480-690 aa.) was the most conserved domain, that showed strong neutral selection pressure for gene purifying with significant population expansion. Antigenicity of both of PvEBP-RII (16.1%) and PvEBP-RIII-V (21.5%) domains were comparatively lower than other P. vivax antigen which expected antigens associated with merozoite invasion. Total IgG recognition level of PvEBP-RII was stronger than PvEBP-RIII-V domain, whereas total IgG inducing level was stronger in PvEBP-RIII-V domain. These results suggest that PvEBP-RII is mainly recognized by natural IgG for innate protection, whereas PvEBP-RIII-V stimulates IgG production activity by B-cell for acquired immunity. Overall, the low antigenicity of both regions in patients with vivax malaria likely reflects genetic polymorphism for strong positive selection in PvEBP-RII and purifying selection in PvEBP-RIII-V domain. These observations pose challenging questions to the selection of EBP and point out the importance of immune pressure and polymorphism required for inclusion of PvEBP as a vaccine candidate.


Assuntos
Variação Genética , Malária Vivax/imunologia , Plasmodium vivax/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Sequência de Aminoácidos , Anticorpos Antiprotozoários/imunologia , Ásia , Humanos , Imunidade Humoral , Malária Vivax/parasitologia , Plasmodium vivax/química , Plasmodium vivax/imunologia , Polimorfismo Genético , Proteínas de Protozoários/química , Seleção Genética , Alinhamento de Sequência
19.
BMC Bioinformatics ; 21(1): 300, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32652926

RESUMO

BACKGROUND: A common yet still manual task in basic biology research, high-throughput drug screening and digital pathology is identifying the number, location, and type of individual cells in images. Object detection methods can be useful for identifying individual cells as well as their phenotype in one step. State-of-the-art deep learning for object detection is poised to improve the accuracy and efficiency of biological image analysis. RESULTS: We created Keras R-CNN to bring leading computational research to the everyday practice of bioimage analysts. Keras R-CNN implements deep learning object detection techniques using Keras and Tensorflow ( https://github.com/broadinstitute/keras-rcnn ). We demonstrate the command line tool's simplified Application Programming Interface on two important biological problems, nucleus detection and malaria stage classification, and show its potential for identifying and classifying a large number of cells. For malaria stage classification, we compare results with expert human annotators and find comparable performance. CONCLUSIONS: Keras R-CNN is a Python package that performs automated cell identification for both brightfield and fluorescence images and can process large image sets. Both the package and image datasets are freely available on GitHub and the Broad Bioimage Benchmark Collection.


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Software , Núcleo Celular , Humanos , Plasmodium vivax/crescimento & desenvolvimento
20.
Mem Inst Oswaldo Cruz ; 115: e200070, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32667462

RESUMO

BACKGROUND Nyssorhynchus deaneorum is a potential malaria vector because it has been shown to be competent to transmit Plasmodium vivax and Plasmodium falciparum, and because it exhibits antropophilic and endophilic behaviors in some regions of the Amazon. This profile makes Ny. deaneorum a useful mosquito for experiments that model Plasmodium-vector interactions in the Amazon. OBJECTIVE Herein we describe how a free-mating colony of Ny. deaneorum has been established using an automated light stimulation system. METHODS Mosquitoes were captured in São Francisco do Guaporé, Rondônia. The F1 generation was reared until adult emergence at which point copulation was induced using an automatic copulation induction system (ACIS). FINDINGS After four generations, natural mating and oviposition began to occur without light stimulation. The number of pupae and adult mosquitoes increased from the F5 to F10 generations. The new Ny. deaneorum colony exhibited susceptibility to P. vivax. MAIN CONCLUSIONS Automated light stimulation is an effective method for establishing an Ny. deaneorum colony under laboratory conditions as it produces enough adults to create a stenogamic colony. The establishment of a stable, P. vivax-susceptible colony of Ny. deaneorum makes it possible to model parasite-vector interactions and to test novel drug therapies that target parasite development in mosquitoes.


Assuntos
Anopheles/parasitologia , Copulação/fisiologia , Malária , Mosquitos Vetores/parasitologia , Oviposição , Animais , Anopheles/fisiologia , Brasil , Feminino , Insetos Vetores/crescimento & desenvolvimento , Insetos Vetores/fisiologia , Plasmodium falciparum , Plasmodium vivax
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