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1.
BMC Infect Dis ; 20(1): 835, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176708

RESUMO

BACKGROUND: The spatial distribution and burden of dengue in sub-Saharan Africa remains highly uncertain, despite high levels of ecological suitability. The goal of this study was to describe the epidemiology of dengue among a cohort of febrile children presenting to outpatient facilities located in areas of western Uganda with differing levels of urbanicity and malaria transmission intensity. METHODS: Eligible children were first screened for malaria using rapid diagnostic tests. Children with a negative malaria result were tested for dengue using a combination NS1/IgM/IgG rapid test (SD Bioline Dengue Duo). Confirmatory testing by RT-PCR was performed in a subset of participants. Antigen-capture ELISA was performed to estimate seroprevalence. RESULTS: Only 6 of 1416 (0.42%) children had a positive dengue rapid test, while none of the RT-PCR results were positive. ELISA testing demonstrated reactive IgG antibodies in 28 (2.2%) participants with the highest prevalence seen at the urban site in Mbarara (19 of 392, 4.9%, p < 0.001). CONCLUSIONS: Overall, these findings suggest that dengue, while present, is an uncommon cause of non-malarial, pediatric febrile illness in western Uganda. Further investigation into the eocological factors that sustain low-level transmission in urban settings are urgently needed to reduce the risk of epidemics.


Assuntos
Vírus da Dengue/genética , Vírus da Dengue/imunologia , Dengue/diagnóstico , Dengue/epidemiologia , Febre/diagnóstico , Adolescente , Criança , Pré-Escolar , Dengue/virologia , Testes Diagnósticos de Rotina/efeitos adversos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Malária/diagnóstico , Malária/epidemiologia , Malária/parasitologia , Masculino , Plasmodium/imunologia , Plasmodium/isolamento & purificação , Prevalência , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Estudos Soroepidemiológicos , Uganda/epidemiologia
2.
BMC Infect Dis ; 20(1): 796, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109111

RESUMO

BACKGROUND: Malaria infection during pregnancy has negative health consequences for both mothers and offspring. Sub-microscopic malaria infection during pregnancy is common in most African countries. We sought to identify factors associated with sub-microscopic placental malaria, and its association with adverse pregnancy outcomes among HIV-negative pregnant women in Dar es Salaam, Tanzania. METHODS: We recruited a cohort of pregnant women during their first trimester and assessed for the occurrence of placental malaria and pregnancy outcomes. The follow-up was done monthly from recruitment until delivery. Histopathology placental malaria positive results were defined as the presence of malaria pigment or parasitized erythrocytes on the slide (histology-positive (HP)), and the sub-microscopic placental infection was defined as positive Plasmodium falciparum DNA by polymerase chain reaction (DNA PCR) amplification in a negative histopathology test. Adverse pregnancy outcomes investigated included low birth weight (birth weight below 2.5 kg), prematurity (live birth below 37 weeks), and small-for-gestational-age (SGA) (live born with a birth weight below 10th percentile for gestational age and sex). Weighted baseline category logit, log-binomial, and log-Poisson models were used to assess factors associated with placental malaria, and its association with adverse pregnancy outcomes. RESULTS: Among 1115 women who had histopathology and DNA PCR performed, 93 (8%) had HP placental infection, and 136 (12%) had the sub-microscopic placental infection. The risk of sub-microscopic placental malaria was greater in women who did not use mosquito prevention methods such as bed nets, fumigation, or mosquito coils (odds ratio (OR) = 1.75; 95% confidence interval (CI): 1.05-2.92; P = 0.03) and in women who were anemic (OR = 1.59; 95% CI: 1.20-2.11; P = 0.001). Women who were underweight had reduced odds of sub-microscopic placental malaria infection (OR = 0.33; 95% CI: 0.17-0.62; P = 0.001). Women who were overweight/obese had 1.48 times higher the odds of HP placental malaria compared to normal weight (OR = 1.48; 95% CI: 1.03-2.11; P = 0.03). HP placental malaria infection was associated with an increased risk of SGA births (RR = 1.30, 95% CI: 0.98-1.72, P = 0.07). In contrast, the sub-microscopic infection was associated with a reduced risk of SGA births (RR = 0.61, 95% CI: 0.43-0.88, P = 0.01). Placental malaria was not associated with low birth weight or prematurity. CONCLUSION: Malaria prevention methods and maternal nutrition status during early pregnancy were important predictors of sub-microscopic placental malaria. More research is needed to understand sub-microscopic placental malaria and the possible mechanisms mediating the association between placental malaria and SGA.


Assuntos
Infecções por HIV/epidemiologia , HIV , Malária/epidemiologia , Placenta/parasitologia , Plasmodium falciparum/genética , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , Adulto , Anemia/etiologia , Peso ao Nascer , Feminino , Seguimentos , Idade Gestacional , Infecções por HIV/virologia , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Malária/complicações , Malária/parasitologia , Gravidez , Complicações Infecciosas na Gravidez/parasitologia , Nascimento Prematuro , Risco , Tanzânia/epidemiologia , Adulto Jovem
3.
PLoS One ; 15(10): e0236616, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33044964

RESUMO

Asexual blood stages of the malaria parasite are readily amenable to genetic modification via homologous recombination, allowing functional studies of parasite genes that are not essential in this part of the life cycle. However, conventional reverse genetics cannot be applied for the functional analysis of genes that are essential during asexual blood-stage replication. Various strategies have been developed for conditional mutagenesis of Plasmodium, including recombinase-based gene deletion, regulatable promoters, and mRNA or protein destabilization systems. Among these, the dimerisable Cre (DiCre) recombinase system has emerged as a powerful approach for conditional gene deletion in P. falciparum. In this system, the bacteriophage Cre is expressed in the form of two separate, enzymatically inactive polypeptides, each fused to a different rapamycin-binding protein. Rapamycin-induced heterodimerization of the two components restores recombinase activity. We have implemented the DiCre system in the rodent malaria parasite P. berghei, and show that rapamycin-induced excision of floxed DNA sequences can be achieved with very high efficiency in both mammalian and mosquito parasite stages. This tool can be used to investigate the function of essential genes not only in asexual blood stages, but also in other parts of the malaria parasite life cycle.


Assuntos
Deleção de Genes , Edição de Genes , Genes de Protozoários/genética , Integrases/metabolismo , Malária/parasitologia , Mutagênese , Plasmodium berghei/genética , Animais , Feminino , Integrases/química , Integrases/genética , Estágios do Ciclo de Vida , Malária/genética , Malária/metabolismo , Camundongos , Camundongos Endogâmicos C57BL
4.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(4): 389-392, 2020 Aug 11.
Artigo em Chinês | MEDLINE | ID: mdl-32935514

RESUMO

OBJECTIVE: To understand the population distribution, density, seasonal fluctuation and nocturnal activity of malaria vectors in Anhui Province from 2016 to 2018, so as to provide a data support for formulating the control strategy for imported malaria during the malaria post-elimination stage. METHODS: The malaria vectors were monitored in 105 counties (cities or districts) of Anhui Province from 2016 to 2018, and the population density, seasonal fluctuation and nocturnal activity of the mosquitoes were observed using the lamp trapping and human bait trapping methods. The density of Anopheles mosquitoes was compared among different years, regions and mosquito-capturing sites. RESULTS: Anopheles mosquitoes were captured in 103 counties (cities or districts) of Anhui Province during the period from 2016 to 2018, and a total of 32 494 mosquitoes were captured using the lamp trapping method and 36 228 captured using the human bait trapping method. All captured mosquitoes were morphologically identified as Anopheles sinensis, and no An. anthropophagus was found. The density of An. sinensis peaked from June to August, and the peak nocturnal activity was found during the period between 19∶00 and 23∶00. Among all mosquito-capturing sites, the highest mosquito density was seen in the livestock and poultry sheds (H = 18.835, P < 0.05). The density of An. sinensis varied significantly in regions in 2016 and 2017 (H = 16.655 and 11.566, P < 0.01), and a low density was found in north of the Huai River. CONCLUSIONS: An. sinensis is widely distributed in Anhui Province, which is the currently predominant malaria vector in the province. During the malaria post-elimination stage, the malaria vector monitoring should be intensified and vector control interventions should be timely adopted in epidemic foci of Anhui Province to prevent the local re-transmission of overseas imported malaria.


Assuntos
Anopheles , Malária , Mosquitos Vetores , Distribuição Animal , Animais , Anopheles/parasitologia , China , Malária/parasitologia , Malária/transmissão , Mosquitos Vetores/parasitologia , Densidade Demográfica , Estações do Ano
5.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(4): 401-404, 2020 Apr 07.
Artigo em Chinês | MEDLINE | ID: mdl-32935517

RESUMO

OBJECTIVE: To analyze the epidemiological characteristics of imported malaria cases in Fujian Province from 2014 to 2018, so as to provide scientific basis for the development of the control strategy for imported malaria. METHODS: The epidemiological data of malaria cases in Fujian Province from 2014 to 2018 were retrieved from the Notifiable Disease Reporting System and Parasitic Disease Information Reporting System of Chinese Center for Disease Control and Prevention, and the classification, origin of infections, temporal distribution, spatial distribution, population distribution, reporting institutions and diagnosis were analyzed. RESULTS: A total of 540 overseas imported malaria cases were reported in Fujian Province from 2014 to 2018, and all cases were laboratory-confirmed, including 398 cases with falciparum malaria, 88 cases with vivax malaria, 38 cases with ovale malaria, 14 cases with malariae malaria and 2 cases with mixed infections. There were 90.56% (489/540) of the imported malaria cases with infections in 27 African countries, 5.92% (32/540) with infections in 5 Asian countries and 3.52% (19/540) with infections in one Oceania country. There was no significant seasonal distribution of the cases, and the imported malaria cases were predominantly detected in Fuzhou City (80.00%, 432/540) and at ages of 20 to 49 years (81.48%, 440/540). Initial diagnosis was predominantly at the city-level medical institutions, and 77.96% (421/540) were diagnosed as malaria at the initial diagnosis institutions. The median duration from onset to initial diagnosis was 2 days and 70.19% (379/540) were diagnosed within 3 days of onset. The interval between initial diagnosis and definitive diagnosis was 0 day, with 85.37% (461/540) definitively diagnosed within 3 days of initial diagnosis. CONCLUSIONS: Overseas imported malaria is a continuous problem challenging the malaria elimination programme of Fujian Province. Improving the healthcare-seeking awareness and the diagnostic capability of healthcare workers, and intensifying the monitoring and management of malaria among overseas labors are strongly recommended.


Assuntos
Doenças Transmissíveis Importadas , Malária , Adulto , China/epidemiologia , Doenças Transmissíveis Importadas/diagnóstico , Doenças Transmissíveis Importadas/epidemiologia , Doenças Transmissíveis Importadas/parasitologia , Humanos , Malária/diagnóstico , Malária/epidemiologia , Malária/parasitologia , Pessoa de Meia-Idade , Plasmodium/fisiologia , Adulto Jovem
6.
PLoS Pathog ; 16(9): e1008799, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32898164

RESUMO

Professional antigen-presenting cells (APCs), like macrophages (Mϕs) and dendritic cells (DCs), are central players in the induction of natural and vaccine-induced immunity to malaria, yet very little is known about the interaction of SPZ with human APCs. Intradermal delivery of whole-sporozoite vaccines reduces their effectivity, possibly due to dermal immunoregulatory effects. Therefore, understanding these interactions could prove pivotal to malaria vaccination. We investigated human APC responses to recombinant circumsporozoite protein (recCSP), SPZ and anti-CSP opsonized SPZ both in monocyte derived MoDCs and MoMϕs. Both MoDCs and MoMϕs readily took up recCSP but did not change phenotype or function upon doing so. SPZ are preferentially phagocytosed by MoMϕs instead of DCs and phagocytosis greatly increased after opsonization. Subsequently MoMϕs show increased surface marker expression of activation markers as well as tolerogenic markers such as Programmed Death-Ligand 1 (PD-L1). Additionally they show reduced motility, produce interleukin 10 and suppressed interferon gamma (IFNγ) production by antigen specific CD8+ T cells. Importantly, we investigated phenotypic responses to SPZ in primary dermal APCs isolated from human skin explants, which respond similarly to their monocyte-derived counterparts. These findings are a first step in enhancing our understanding of pre-erythrocytic natural immunity and the pitfalls of intradermal vaccination-induced immunity.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Macrófagos/imunologia , Malária/imunologia , Plasmodium berghei/imunologia , Proteínas de Protozoários/imunologia , Pele/imunologia , Esporozoítos/imunologia , Animais , Células Cultivadas , Feminino , Humanos , Macrófagos/parasitologia , Malária/parasitologia , Camundongos , Pele/parasitologia
7.
PLoS Pathog ; 16(9): e1008739, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32946522

RESUMO

Malaria-causing Plasmodium parasites traverse the mosquito midgut cells to establish infection at the basal side of the midgut. This dynamic process is a determinant of mosquito vector competence, yet the kinetics of the parasite migration is not well understood. Here we used transgenic mosquitoes of two Anopheles species and a Plasmodium berghei fluorescence reporter line to track parasite passage through the mosquito tissues at high spatial resolution. We provide new quantitative insight into malaria parasite invasion in African and Indian Anopheles species and propose that the mosquito complement-like system contributes to the species-specific dynamics of Plasmodium invasion.


Assuntos
Anopheles/parasitologia , Sistema Digestório/parasitologia , Interações Hospedeiro-Parasita , Malária/transmissão , Mosquitos Vetores/patogenicidade , Plasmodium berghei/fisiologia , Animais , Anopheles/crescimento & desenvolvimento , Feminino , Malária/parasitologia , Camundongos , Especificidade da Espécie
8.
PLoS One ; 15(9): e0238323, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32898853

RESUMO

India, a persistently significant contributor to the global malaria burden, rolled out several anti-malaria interventions at the national and state level to control and recently, to eliminate the disease. Odisha, the eastern Indian state with the highest malaria burden experienced substantial gains shown by various anti-malaria initiatives implemented under the National Vector-borne Disease Control Programme (NVBDCP). However, recalcitrant high-transmission "pockets" of malaria persist in hard-to-reach stretches of the state, characterised by limited access to routine malaria surveillance and the forested hilly topography favouring unbridled vector breeding. The prevalence of asymptomatic malaria in such pockets serves as perpetual malaria reservoir, thus hindering its elimination. Therefore, a project with the acronym DAMaN was initiated since 2017 by state NVBDCP, targeting locally identified high endemic 'pockets' in 23 districts. DAMaN comprised biennial mass screening and treatment, provisioning of long-lasting insecticidal net (LLIN) and behavioural change communication. Subsequently, to inform policy, assessment of DAMaN was conceived that aims to estimate the coverage of the various components of the project; the prevalence of malaria, even at sub-patent level especially among pregnant/lactating women and children; and its impact on malaria incidence. A survey of DAMaN beneficiaries will measure coverage; and knowledge and practices related to LLIN; along with collection of blood specimens from a probability sample. A multi-stage stratified clustered sample of 2228 households (~33% having pregnant/lactating women) will be selected from 6 DAMaN districts. Routine DAMaN project data (2017-2018) and NVBDCP data (2013-2018) will be extracted. Rapid Diagnostic Test, Polymerase Chain Reaction and blood smear microscopy will be conducted to detect malarial parasitemia. In addition to measuring DAMaN's coverage and malarial prevalence in DAMaN pockets, its impact will be estimated using pre-post differences and Interrupted Time Series analysis using 2017 as the "inflection" point. The assessment may help to validate the unique strategies employed by DAMaN.


Assuntos
Antimaláricos/uso terapêutico , Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Malária/epidemiologia , Malária/prevenção & controle , Controle de Mosquitos/organização & administração , Controle de Mosquitos/normas , Plasmodium malariae/efeitos dos fármacos , Adolescente , Criança , Pré-Escolar , Feminino , Governo , Humanos , Incidência , Índia/epidemiologia , Lactente , Análise de Séries Temporais Interrompida , Malária/parasitologia , Malária/transmissão , Gravidez , Inquéritos e Questionários
9.
PLoS One ; 15(9): e0230984, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32946446

RESUMO

Insecticide resistance genes are often associated with pleiotropic effects on various mosquito life-history traits. However, very little information is available on the impact of insecticide resistance on blood feeding process in mosquitoes. Here, using two recently detected DNA-based metabolic markers in the major malaria vector, An. funestus, we investigated how metabolic resistance genes could affect the blood meal intake. After allowing both the field F1 and lab F8 Anopheles funestus strains to feed on the human arm for 30 minutes, we assessed the association between key parameters of blood meal process including, probing time, feeding duration, blood feeding success, blood meal size, and markers of glutathione S-transferase (L119F-GSTe2) and cytochrome P450 (CYP6P9a_R)-mediated metabolic resistance. None of the parameters of blood meal process was associated with L119F-GSTe2 genotypes. By contrast, for CYP6P9a_R, homozygous resistant mosquitoes were significantly more able to blood-feed than homozygous susceptible (OR = 3.3; CI 95%: 1.4-7.7; P = 0.01) mosquitoes. Moreover, the volume of blood meal ingested by CYP6P9a-SS mosquitoes was lower than that of CYP6P9a-RS (P<0.004) and of CYP6P9a-RR (P<0.006). This suggests that CYP6P9a gene is inked with the feeding success and blood meal size of An. funestus. However, no correlation was found in the expression of CYP6P9a and that of genes encoding for salivary proteins involved in blood meal process. This study suggests that P450-based metabolic resistance may influence the blood feeding process of Anopheles funestus mosquito and consequently its ability to transmit malaria parasites.


Assuntos
Anopheles/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Glutationa Transferase/metabolismo , Proteínas de Insetos/metabolismo , Mosquitos Vetores/metabolismo , Animais , Anopheles/efeitos dos fármacos , Anopheles/genética , Anopheles/parasitologia , Sangue/metabolismo , Camarões , Sistema Enzimático do Citocromo P-450/genética , Comportamento Alimentar , Feminino , Glutationa Transferase/genética , Humanos , Proteínas de Insetos/genética , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Malária/parasitologia , Malária/prevenção & controle , Malária/transmissão , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/genética , Mosquitos Vetores/parasitologia , Plasmodium/patogenicidade , Piretrinas/farmacologia , Proteínas e Peptídeos Salivares/metabolismo
10.
Medicine (Baltimore) ; 99(36): e22044, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899064

RESUMO

BACKGROUND: Malaria remains a global health threat for centuries. In recent years, a rising resistance of Plasmodium falciparum to current standard artemisinin-based combination therapies (ACTs) leads to increasing treatment failures and requires for optimized treatment. Here, we intend to make a systematic review and meta-analysis of optimizing treatment for malaria, so as to find a potential optimal treatment. METHODS: We will search electronic databases: the Cochrane Infectious Diseases Group (CIDG) Specialized Register, the Cochrane Central Register of Controlled Trials (CEN-TRAL), PubMed, Embase, Web of Science from their inception to 1 July, 2020. We will also search International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov, and contact with authors when necessary. Two authors will independently collect and select data, and the statistical analyses will be conducted by Revman V.5.3 software. RESULTS: We will evaluate efficacy and safety of modified ACTs for uncomplicate malaria, comparing with standard ACTs in all eligible clinical studies. CONCLUSION: In this study, we will offer clinical evidence for optimizing treatment for malaria. REGISTRATION NUMBER: INPLASY202070115.


Assuntos
Anti-Infecciosos/uso terapêutico , Artemisininas/uso terapêutico , Malária/tratamento farmacológico , Antimaláricos/uso terapêutico , Terapia Combinada , Feminino , Humanos , Malária/epidemiologia , Malária/parasitologia , Masculino , Plasmodium falciparum/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Segurança , Falha de Tratamento , Resultado do Tratamento
11.
PLoS Pathog ; 16(8): e1008230, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32797076

RESUMO

Neutrophil extracellular traps (NETs) evolved as a unique effector mechanism contributing to resistance against infection that can also promote tissue damage in inflammatory conditions. Malaria infection can trigger NET release, but the mechanisms and consequences of NET formation in this context remain poorly characterized. Here we show that patients suffering from severe malaria had increased amounts of circulating DNA and increased neutrophil elastase (NE) levels in plasma. We used cultured erythrocytes and isolated human neutrophils to show that Plasmodium-infected red blood cells release macrophage migration inhibitory factor (MIF), which in turn caused NET formation by neutrophils in a mechanism dependent on the C-X-C chemokine receptor type 4 (CXCR4). NET production was dependent on histone citrullination by peptidyl arginine deiminase-4 (PAD4) and independent of reactive oxygen species (ROS), myeloperoxidase (MPO) or NE. In vitro, NETs functioned to restrain parasite dissemination in a mechanism dependent on MPO and NE activities. Finally, C57/B6 mice infected with P. berghei ANKA, a well-established model of cerebral malaria, presented high amounts of circulating DNA, while treatment with DNAse increased parasitemia and accelerated mortality, indicating a role for NETs in resistance against Plasmodium infection.


Assuntos
Eritrócitos/imunologia , Armadilhas Extracelulares/imunologia , Fatores Inibidores da Migração de Macrófagos/metabolismo , Malária/imunologia , Neutrófilos/imunologia , Plasmodium/imunologia , Receptores CXCR4/metabolismo , Animais , Eritrócitos/metabolismo , Eritrócitos/parasitologia , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/parasitologia , Humanos , Malária/metabolismo , Malária/parasitologia , Malária/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Neutrófilos/parasitologia , Parasitemia/imunologia , Parasitemia/metabolismo , Parasitemia/parasitologia , Parasitemia/patologia
12.
Science ; 369(6507): 1128-1132, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32855340

RESUMO

Hemocytes limit the capacity of mosquitoes to transmit human pathogens. Here we profile the transcriptomes of 8506 hemocytes of Anopheles gambiae and Aedes aegypti mosquito vectors. Our data reveal the functional diversity of hemocytes, with different subtypes of granulocytes expressing distinct and evolutionarily conserved subsets of effector genes. A previously unidentified cell type in An. gambiae, which we term "megacyte," is defined by a specific transmembrane protein marker (TM7318) and high expression of lipopolysaccharide-induced tumor necrosis factor-α transcription factor 3 (LL3). Knockdown experiments indicate that LL3 mediates hemocyte differentiation during immune priming. We identify and validate two main hemocyte lineages and find evidence of proliferating granulocyte populations. This atlas of medically relevant invertebrate immune cells at single-cell resolution identifies cellular events that underpin mosquito immunity to malaria infection.


Assuntos
Aedes/imunologia , Anopheles/imunologia , Hemócitos/imunologia , Imunidade Celular , Malária/transmissão , Mosquitos Vetores/imunologia , Aedes/genética , Animais , Anopheles/genética , Feminino , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Granulócitos/imunologia , Hemócitos/metabolismo , Malária/imunologia , Malária/parasitologia , Camundongos , Mosquitos Vetores/genética , RNA-Seq , Análise de Célula Única
13.
PLoS One ; 15(8): e0235401, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817665

RESUMO

BACKGROUND: Current malaria control and elimination strategies rely mainly on efficacious antimalarial drugs. However, drug resistance is a major threat facing malaria control programs. Determination of drug resistance molecular markers is useful in the monitoring and surveillance of malaria drug efficacy. This study aimed to determine the mutations and haplotypes frequencies of different genes linked with antimalarial drug resistance in certain areas in Sudan. METHODS: A total of 226 dried blood spots (DBS) of microscopically diagnosed P. falciparum isolates were collected from Khartoum and three other areas in Sudan during 2015-2017. Plasmodium falciparum confirmation and multiplicity of infection was assessed using the Sanger's 101 SNPs-barcode and speciation was confirmed using regions of the parasite mitochondria. Molecular genotyping of drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, exonuclease, Pfk13, parasite genetic background (PGB) (Pfarps10, ferredoxin, Pfcrt, Pfmdr2)) was also performed. All genotypes were generated by selective regions amplicon sequencing of the parasite genome using the Illumina MiSeq platform at the Wellcome Sanger Institute, UK then genotypes were translated into drug resistance haplotypes and species determination. FINDINGS: In total 225 samples were confirmed to be P. falciparum. A higher proportion of multiplicity of infection was observed in Gezira (P<0.001) based on the Sanger 101 SNPs -barcode. The overall frequency of mutant haplotype Pfcrt 72-76 CVIET was 71.8%. For Pfmdr1, N86Y was detected in 53.6%, Y184F was observed in 88.1% and D1246Y was detected in 1.5% of the samples. The most frequently observed haplotype was YFD 47.4%. For Pfdhfr (codons 51, 59,108,164), the ICNI haplotype was the most frequent (80.7%) while for Pfdhps (codons 436, 437, 540, 581, 613) the (SGEAA) was most frequent haplotype (41%). The Quadruple mutation (dhfr N51I, S108N + dhps A437G, K540E) was the highest frequent combined mutation (33.9%). In Pfkelch13 gene, 18 non-synonymous mutations were detected, 7 of them were detected in other African countries. The most frequent Pfk13 mutation was E433D detected in four samples. All of the Pfk13 mutant alleles have not been reported to belong to mutations associated with delayed parasite clearance in Southeast Asia. PGB mutations were detected only in Pfcrt N326S\I (46.3%) and Pfcrt I356T (8.2%). The exonuclease mutation was not detected. There was no significant variation in mutant haplotypes between study areas. CONCLUSIONS: There was high frequency of mutations in Pfcrt, Pfdhfr and Pfdhps in this study. These mutations are associated with chloroquine and sulfadoxine-pyrimethamine (SP) resistance. Many SNPs in Pfk13 not linked with delayed parasite clearance were observed. The exonuclease E415G mutation which is linked with piperaquine resistance was not reported.


Assuntos
Resistência a Medicamentos/genética , Malária/parasitologia , Mutação , Plasmodium falciparum/genética , Adolescente , Antimaláricos/farmacologia , Criança , Cloroquina/farmacologia , Feminino , Humanos , Malária/epidemiologia , Masculino , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/patogenicidade , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Pirimetamina/farmacologia , Sudão , Sulfadoxina/farmacologia , Tetra-Hidrofolato Desidrogenase/genética , Tetra-Hidrofolato Desidrogenase/metabolismo , Adulto Jovem
14.
PLoS Pathog ; 16(8): e1008717, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32745123

RESUMO

Hepatocystis is a genus of single-celled parasites infecting, amongst other hosts, monkeys, bats and squirrels. Although thought to have descended from malaria parasites (Plasmodium spp.), Hepatocystis spp. are thought not to undergo replication in the blood-the part of the Plasmodium life cycle which causes the symptoms of malaria. Furthermore, Hepatocystis is transmitted by biting midges, not mosquitoes. Comparative genomics of Hepatocystis and Plasmodium species therefore presents an opportunity to better understand some of the most important aspects of malaria parasite biology. We were able to generate a draft genome for Hepatocystis sp. using DNA sequencing reads from the blood of a naturally infected red colobus monkey. We provide robust phylogenetic support for Hepatocystis sp. as a sister group to Plasmodium parasites infecting rodents. We show transcriptomic support for a lack of replication in the blood and genomic support for a complete loss of a family of genes involved in red blood cell invasion. Our analyses highlight the rapid evolution of genes involved in parasite vector stages, revealing genes that may be critical for interactions between malaria parasites and mosquitoes.


Assuntos
Apicomplexa/genética , Sangue/parasitologia , Colobus/parasitologia , Malária/veterinária , Doenças dos Macacos/parasitologia , Plasmodium/genética , Infecções Protozoárias em Animais/parasitologia , Animais , Apicomplexa/classificação , Apicomplexa/fisiologia , Genoma de Protozoário , Malária/sangue , Malária/parasitologia , Doenças dos Macacos/sangue , Filogenia , Plasmodium/classificação , Plasmodium/fisiologia , Infecções Protozoárias em Animais/sangue , Transcriptoma
15.
Nat Med ; 26(9): 1411-1416, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32770167

RESUMO

The burden of malaria is heavily concentrated in sub-Saharan Africa (SSA) where cases and deaths associated with COVID-19 are rising1. In response, countries are implementing societal measures aimed at curtailing transmission of SARS-CoV-22,3. Despite these measures, the COVID-19 epidemic could still result in millions of deaths as local health facilities become overwhelmed4. Advances in malaria control this century have been largely due to distribution of long-lasting insecticidal nets (LLINs)5, with many SSA countries having planned campaigns for 2020. In the present study, we use COVID-19 and malaria transmission models to estimate the impact of disruption of malaria prevention activities and other core health services under four different COVID-19 epidemic scenarios. If activities are halted, the malaria burden in 2020 could be more than double that of 2019. In Nigeria alone, reducing case management for 6 months and delaying LLIN campaigns could result in 81,000 (44,000-119,000) additional deaths. Mitigating these negative impacts is achievable, and LLIN distributions in particular should be prioritized alongside access to antimalarial treatments to prevent substantial malaria epidemics.


Assuntos
Antimaláricos/uso terapêutico , Infecções por Coronavirus/epidemiologia , Malária/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/parasitologia , Infecções por Coronavirus/virologia , Humanos , Inseticidas/uso terapêutico , Malária/complicações , Malária/parasitologia , Malária/virologia , Controle de Mosquitos , Pneumonia Viral/complicações , Pneumonia Viral/parasitologia , Pneumonia Viral/virologia , Saúde Pública
17.
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
18.
Mem Inst Oswaldo Cruz ; 115: e200043, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32667459

RESUMO

BACKGROUND The number of malaria cases in Roraima nearly tripled from 2016 to 2018. The capital, Boa Vista, considered a low-risk area for malaria transmission, reported an increasing number of autochthonous and imported cases. OBJECTIVES This study describes a spatial analysis on malaria cases in an urban region of Boa Vista, which sought to identify the autochthonous and imported cases and associated them with Anopheles habitats and the potential risk of local transmission. METHODS In a cross-sectional study at the Polyclinic Cosme e Silva, 520 individuals were interviewed and diagnosed with malaria by microscopic examination. Using a global positional system, the locations of malaria cases by type and origin and the breeding sites of anopheline vectors were mapped and the risk of malaria transmission was evaluated by spatial point pattern analysis. FINDINGS Malaria was detected in 57.5% of the individuals and there was a disproportionate number of imported cases (90.6%) linked to Brazilian coming from gold mining sites in Venezuela and Guyana. MAIN CONCLUSIONS The increase in imported malaria cases circulating in the west region of Boa Vista, where there are positive breeding sites for the main vectors, may represent a potential condition for increased autochthonous malaria transmission in this space.


Assuntos
Anopheles/parasitologia , Malária/diagnóstico , Malária/transmissão , Mineradores/estatística & dados numéricos , Mosquitos Vetores/parasitologia , Plasmodium/isolamento & purificação , Viagem , Adulto , Animais , Anopheles/classificação , Brasil/epidemiologia , Estudos Transversais , Feminino , Sistemas de Informação Geográfica , Ouro , Guiana , Humanos , Malária/epidemiologia , Malária/parasitologia , Masculino , Pessoa de Meia-Idade , Plasmodium/classificação , Análise Espacial , População Urbana , Venezuela
19.
Cytometry A ; 97(9): 872-881, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32686260

RESUMO

Malaria is a threat to human mankind and kills about half a million people every year. On the other hand, COVID-19 resulted in several hundred thousand deaths since December 2019 and remains without an efficient and safe treatment. The antimalarials chloroquine (CQ) and its analog, hydroxychloroquine (HCQ), have been tested for COVID-19 treatment, and several conflicting evidence has been obtained. Therefore, the aim of this review was to summarize the evidence regarding action mechanisms of these compounds against Plasmodium and SARS-CoV-2 infection, together with cytometry applications. CQ and HCQ act on the renin angiotensin system, with possible implications on the cardiorespiratory system. In this context, flow and image cytometry emerge as powerful technologies to investigate the mechanism of therapeutic candidates, as well as for the identification of the immune response and prognostics of disease severity. Data from the large randomized trials support the conclusion that CQ and HCQ do not provide any clinical improvements in disease severity and progression of SARS-CoV-2 patients, as well as they do not present any solid evidence of increased serious side effects. These drugs are safe and effective antimalarials agents, but in SARS-CoV-2 patients, they need further studies in the context of clinical trials. © 2020 International Society for Advancement of Cytometry.


Assuntos
Antimaláricos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Malária/tratamento farmacológico , Plasmodium/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Animais , Antimaláricos/efeitos adversos , Antivirais/efeitos adversos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Cloroquina/efeitos adversos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Citometria de Fluxo , Interações entre Hospedeiro e Microrganismos , Interações Hospedeiro-Parasita , Humanos , Malária/diagnóstico , Malária/imunologia , Malária/parasitologia , Pandemias , Plasmodium/imunologia , Plasmodium/patogenicidade , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Resultado do Tratamento
20.
Proc Natl Acad Sci U S A ; 117(28): 16546-16556, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601225

RESUMO

During blood-stage development, malaria parasites are challenged with the detoxification of enormous amounts of heme released during the proteolytic catabolism of erythrocytic hemoglobin. They tackle this problem by sequestering heme into bioinert crystals known as hemozoin. The mechanisms underlying this biomineralization process remain enigmatic. Here, we demonstrate that both rodent and human malaria parasite species secrete and internalize a lipocalin-like protein, PV5, to control heme crystallization. Transcriptional deregulation of PV5 in the rodent parasite Plasmodium berghei results in inordinate elongation of hemozoin crystals, while conditional PV5 inactivation in the human malaria agent Plasmodium falciparum causes excessive multidirectional crystal branching. Although hemoglobin processing remains unaffected, PV5-deficient parasites generate less hemozoin. Electron diffraction analysis indicates that despite the distinct changes in crystal morphology, neither the crystalline order nor unit cell of hemozoin are affected by impaired PV5 function. Deregulation of PV5 expression renders P. berghei hypersensitive to the antimalarial drugs artesunate, chloroquine, and atovaquone, resulting in accelerated parasite clearance following drug treatment in vivo. Together, our findings demonstrate the Plasmodium-tailored role of a lipocalin family member in hemozoin formation and underscore the heme biomineralization pathway as an attractive target for therapeutic exploitation.


Assuntos
Heme/metabolismo , Lipocalinas/metabolismo , Malária/parasitologia , Plasmodium berghei/metabolismo , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Sequência de Aminoácidos , Animais , Hemeproteínas/genética , Hemeproteínas/metabolismo , Humanos , Lipocalinas/química , Lipocalinas/genética , Malária/metabolismo , Camundongos , Plasmodium berghei/química , Plasmodium berghei/genética , Plasmodium falciparum/química , Plasmodium falciparum/genética , Proteínas de Protozoários/química , Proteínas de Protozoários/genética
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