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1.
Malar J ; 20(1): 442, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34801056

RESUMO

Malaria is a complex parasitic disease, caused by Plasmodium spp. More than a century after the discovery of malaria parasites, this disease continues to pose a global public health problem and the pathogenesis of the severe forms of malaria remains incompletely understood. Extracellular vesicles (EVs), including exosomes and microvesicles, have been increasingly researched in the field of malaria in a bid to fill these knowledge gaps. EVs released from Plasmodium-infected red blood cells and other host cells during malaria infection are now believed to play key roles in disease pathogenesis and are suggested as vital components of the biology of Plasmodium spp. Malaria-derived EVs have been identified as potential disease biomarkers and therapeutic tools. In this review, key findings of malaria EV studies over the last 20 years are summarized and critically analysed. Outstanding areas of research into EV biology are identified. Unexplored EV research foci for the future that will contribute to consolidating the potential for EVs as agents in malaria prevention and control are proposed.


Assuntos
Vesículas Extracelulares/fisiologia , Malária/parasitologia , Plasmodium/fisiologia , Humanos
2.
Sci Rep ; 11(1): 15337, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321525

RESUMO

The epidemiology of human malaria differs considerably between and within geographic regions due, in part, to variability in mosquito species behaviours. Recently, the WHO emphasised stratifying interventions using local surveillance data to reduce malaria. The usefulness of vector surveillance is entirely dependent on the biases inherent in the sampling methods deployed to monitor mosquito populations. To understand and interpret mosquito surveillance data, the frequency of use of malaria vector collection methods was analysed from a georeferenced vector dataset (> 10,000 data records), extracted from 875 manuscripts across Africa, the Americas and the Asia-Pacific region. Commonly deployed mosquito collection methods tend to target anticipated vector behaviours in a region to maximise sample size (and by default, ignoring other behaviours). Mosquito collection methods targeting both host-seeking and resting behaviours were seldomly deployed concurrently at the same site. A balanced sampling design using multiple methods would improve the understanding of the range of vector behaviours, leading to improved surveillance and more effective vector control.


Assuntos
Anopheles/fisiologia , Comportamento Animal/fisiologia , Malária/transmissão , Mosquitos Vetores/fisiologia , África/epidemiologia , Animais , Anopheles/parasitologia , Ásia/epidemiologia , Humanos , Malária/epidemiologia , Mosquitos Vetores/parasitologia , América do Norte/epidemiologia , Plasmodium/fisiologia , América do Sul/epidemiologia
3.
Malar J ; 20(1): 297, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215257

RESUMO

BACKGROUND: Recent genome wide analysis studies have identified a strong association between single nucleotide variations within the human ATP2B4 gene and susceptibility to severe malaria. The ATP2B4 gene encodes the plasma membrane calcium ATPase 4 (PMCA4), which is responsible for controlling the physiological level of intracellular calcium in many cell types, including red blood cells (RBCs). It is, therefore, postulated that genetic differences in the activity or expression level of PMCA4 alters intracellular Ca2+ levels and affects RBC hydration, modulating the invasion and growth of the Plasmodium parasite within its target host cell. METHODS: In this study the course of three different Plasmodium spp. infections were examined in mice with systemic knockout of Pmca4 expression. RESULTS: Ablation of PMCA4 reduced the size of RBCs and their haemoglobin content but did not affect RBC maturation and reticulocyte count. Surprisingly, knockout of PMCA4 did not significantly alter peripheral parasite burdens or the dynamics of blood stage Plasmodium chabaudi infection or reticulocyte-restricted Plasmodium yoelii infection. Interestingly, although ablation of PMCA4 did not affect peripheral parasite levels during Plasmodium berghei infection, it did promote slight protection against experimental cerebral malaria, associated with a minor reduction in antigen-experienced T cell accumulation in the brain. CONCLUSIONS: The finding suggests that PMCA4 may play a minor role in the development of severe malarial complications, but that this appears independent of direct effects on parasite invasion, growth or survival within RBCs.


Assuntos
Resistência à Doença/genética , Malária/genética , ATPases Transportadoras de Cálcio da Membrana Plasmática/genética , Plasmodium/fisiologia , Animais , Membrana Celular , Malária/sangue , Malária/parasitologia , Malária Cerebral/genética , Malária Cerebral/parasitologia , Camundongos , Camundongos Knockout , ATPases Transportadoras de Cálcio da Membrana Plasmática/metabolismo , Plasmodium berghei/fisiologia , Plasmodium chabaudi/fisiologia , Plasmodium yoelii/fisiologia
4.
Front Immunol ; 12: 661241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122419

RESUMO

As a relatively successful pathogen, several parasites can establish long-term infection in host. This "harmonious symbiosis" status relies on the "precise" manipulation of host immunity and metabolism, however, the underlying mechanism is still largely elusive. Immunometabolism is an emerging crossed subject in recent years. It mainly discusses the regulatory mechanism of metabolic changes on reprogramming the key transcriptional and post-transcriptional events related to immune cell activation and effect, which provides a novel insight for understanding how parasites regulate the infection and immunity in hosts. The present study reviewed the current research progress on metabolic reprogramming mechanism exploited by parasites to modulate the function in various immune cells, highlighting the future exploitation of key metabolites or metabolic events to clarify the underlying mechanism of anti-parasite immunity and design novel intervention strategies against parasitic infection.


Assuntos
Células Dendríticas/imunologia , Linfócitos/imunologia , Macrófagos/imunologia , Doenças Parasitárias/imunologia , Plasmodium/imunologia , Schistosoma/imunologia , Trypanosoma/imunologia , Animais , Células Dendríticas/metabolismo , Células Dendríticas/parasitologia , Interações Hospedeiro-Parasita/imunologia , Humanos , Linfócitos/metabolismo , Linfócitos/parasitologia , Macrófagos/metabolismo , Macrófagos/parasitologia , Doenças Parasitárias/metabolismo , Doenças Parasitárias/parasitologia , Plasmodium/fisiologia , Schistosoma/fisiologia , Trypanosoma/fisiologia
5.
Biochem J ; 478(13): 2697-2713, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34133730

RESUMO

During malarial infection, Plasmodium parasites digest human hemoglobin to obtain free amino acids for protein production and maintenance of osmotic pressure. The Plasmodium M1 and M17 aminopeptidases are both postulated to have an essential role in the terminal stages of the hemoglobin digestion process and are validated drug targets for the design of new dual-target anti-malarial compounds. In this study, we profiled the substrate specificity fingerprints and kinetic behaviors of M1 and M17 aminopeptidases from Plasmodium falciparum and Plasmodium vivax, and the mouse model species, Plasmodium berghei. We found that although the Plasmodium M1 aminopeptidases share a largely similar, broad specificity at the P1 position, the P. falciparum M1 displays the greatest diversity in specificity and P. berghei M1 showing a preference for charged P1 residues. In contrast, the Plasmodium M17 aminopeptidases share a highly conserved preference for hydrophobic residues at the P1 position. The aminopeptidases also demonstrated intra-peptide sequence specificity, particularly the M1 aminopeptidases, which showed a definitive preference for peptides with fewer negatively charged intrapeptide residues. Overall, the P. vivax and P. berghei enzymes had a faster substrate turnover rate than the P. falciparum enzymes, which we postulate is due to subtle differences in structural dynamicity. Together, these results build a kinetic profile that allows us to better understand the catalytic nuances of the M1 and M17 aminopeptidases from different Plasmodium species.


Assuntos
Aminopeptidases/metabolismo , Peptídeos/metabolismo , Plasmodium/enzimologia , Proteínas de Protozoários/metabolismo , Aminopeptidases/classificação , Aminopeptidases/genética , Animais , Biocatálise/efeitos dos fármacos , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Cinética , Leucina/análogos & derivados , Leucina/farmacologia , Malária/parasitologia , Camundongos , Plasmodium/genética , Plasmodium/fisiologia , Plasmodium berghei/enzimologia , Plasmodium berghei/genética , Plasmodium falciparum/enzimologia , Plasmodium falciparum/genética , Plasmodium vivax/enzimologia , Plasmodium vivax/genética , Inibidores de Proteases/farmacologia , Proteínas de Protozoários/genética , Proteínas Recombinantes/metabolismo , Especificidade da Espécie , Especificidade por Substrato
6.
Parasitol Int ; 83: 102372, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33933652

RESUMO

A key characteristic of eukaryotic cells is the presence of organelles with discrete boundaries and functions. Such subcellular compartmentalization into organelles necessitates platforms for communication and material exchange between each other which often involves vesicular trafficking and associated processes. Another way is via the close apposition between organellar membranes, called membrane contact sites (MCSs). Apart from lipid transfer, MCSs have been implicated to mediate in various cellular processes including ion transport, apoptosis, and organelle dynamics. In mammalian and yeast cells, contact sites have been reported between the membranes of the following: the endoplasmic reticulum (ER) and the plasma membrane (PM), ER and the Golgi apparatus, ER and endosomes (i.e., vacuoles, lysosomes), ER and lipid droplets (LD), the mitochondria and vacuoles, the nucleus and vacuoles, and the mitochondria and lipid droplets, whereas knowledge of MCSs in non-model organisms such as protozoan parasites is extremely limited. Growing evidence suggests that MCSs play more general and conserved roles in cell physiology. In this mini review, we summarize and discuss representative MCSs in divergent parasitic protozoa, and highlight the universality, diversity, and the contribution of MCSs to parasitism.


Assuntos
Entamoeba histolytica/fisiologia , Giardia lamblia/fisiologia , Plasmodium/fisiologia , Transdução de Sinais/fisiologia , Toxoplasma/fisiologia , Trypanosoma brucei brucei/fisiologia , Membrana Celular/fisiologia , Organelas/fisiologia
7.
Trends Parasitol ; 37(7): 638-650, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33941492

RESUMO

Parasites of the genus Plasmodium cause human and animal malaria, leading to significant health and economic impacts. A key aspect of the complex life cycle of Plasmodium parasites is the invasion of the parasite into its host cell, which is mediated by secretory organelles. The largest of these organelles, the rhoptry, undergoes rapid and profound physiological changes when it secretes its contents during merozoite and sporozoite invasion of the host erythrocyte and hepatocyte, respectively. Here we discuss recent advancements in our understanding of the dynamic rhoptry biology during the parasite's invasive stages, with a focus on the roles of cytosolically exposed rhoptry-interacting proteins (C-RIPs). We explore potential similarities between the molecular mechanisms driving merozoite and sporozoite rhoptry function.


Assuntos
Estágios do Ciclo de Vida/fisiologia , Plasmodium/fisiologia , Proteínas de Protozoários/metabolismo , Interações Hospedeiro-Patógeno , Plasmodium/patogenicidade
8.
Trends Parasitol ; 37(7): 581-584, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33941493

RESUMO

Crystalloids are malaria parasite organelles exclusive to the ookinete and young oocyst life stages that infect the mosquito. The organelles have key roles in sporozoite development and infectivity but the way this is facilitated on a molecular level remains poorly understood. Recent discoveries have shed new light on these processes.


Assuntos
Estágios do Ciclo de Vida/fisiologia , Malária/parasitologia , Malária/transmissão , Organelas/metabolismo , Plasmodium/fisiologia , Plasmodium/patogenicidade , Animais , Humanos , Plasmodium/citologia
9.
Mol Biochem Parasitol ; 243: 111372, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33961918

RESUMO

Malaria parasites are obligate intracellular pathogens that live in human red blood cells harbored by a parasitophorous vacuole. The parasites need to exit from the red blood cell to continue life-cycle progression and ensure human-to-mosquito transmission. Two types of blood stages are able to lyse the enveloping red blood cell to mediate egress, the merozoites and the gametocytes. The intraerythrocytic parasites exit the red blood cell via an inside-out mode during which the membrane of the parasitophorous vacuole ruptures prior to the red blood cell membrane. Membrane rupture is initiated by the exocytosis of specialized secretory vesicles following the perception of egress triggers. The molecular mechanisms of red blood cell egress have particularly been studied in malaria gametocytes. Upon activation by external factors, gametocytes successively discharge at least two types of vesicles, the osmiophilic bodies needed to rupture the parasitophorous vacuole membrane and recently identified egress vesicles that are important for the perforation of the erythrocyte membrane. In recent years, important components of the signaling cascades leading to red blood cell egress have been investigated and several proteins of the osmiophilic bodies have been identified. We here report on the newest findings on the egress of gametocytes from the red blood cell. We further focus on the content and function of the egress-related vesicles and discuss the molecular machinery that might drive vesicle discharge.


Assuntos
Eritrócitos/parasitologia , Interações Hospedeiro-Parasita/fisiologia , Plasmodium/patogenicidade , Proteínas SNARE/metabolismo , Vesículas Secretórias/metabolismo , Animais , Membrana Celular/metabolismo , Membrana Celular/parasitologia , Exocitose , Plasmodium/fisiologia , Proteínas de Protozoários/metabolismo
10.
Acta Trop ; 220: 105957, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33979637

RESUMO

Intraerythrocytic parasites are traditionally identified by the microscopic examination of Giemsa-stained blood smears. However, this method does not always allow for the identification of individual species in goat's RBCs. Moreover, its unreliability in detecting low levels of parasitemia makes it unsuitable for epidemiological investigations and leaves goat farms vulnerable to potential outbreaks. In the present study, a novel multiplex PCR (mPCR) targeting the cytochrome c oxidase subunit I (COI) gene was developed to detect and subsequently differentiate Plasmodium caprae, Theileria luwenshuni, and Babesia spp. The specificity of each primer set was assessed both in silico and with a panel of DNA samples from the hosts themselves and other goat hemoparasites. Amplicons generated from each pair of primers were 664, 555, and 320-bp for P. caprae, Babesia spp., and T. luwenshuni, respectively. These products were further confirmed by sequencing. Our novel mPCR reactions successfully demonstrated the accurate and simultaneous amplification of the three parasites' DNA samples. The current mPCR method showed no cross-amplification with unintended targets. The detection limit of the mPCR in this study was 108 parasites' DNA copies per reaction. The current mPCR was able to detect the minimum parasitemia of approximately 0.001%, 0.000005%, 0.00001% for P. caprae, Babesia spp. and T. luwenshuni, respectively. The diagnostic specificity in the detection of P. caprae and T. luwenshuni ranged from 94.9 to 100 %. The mPCR was further applied to a collection of field blood samples from five provinces in Thailand to validate its reliability and applicability. The results demonstrated the successful detection of P. caprae, Babesia spp. and T. luwenshuni in goat samples with the same sensitivity levels as conventional PCR methods. This study also confirmed the presence of T. luwenshuni and Babesia spp. in Thai goats. The current mPCR method offers an alternative for the diagnosis of P. caprae, T. luwenshuni, and Babesia spp., either single or under co-infection conditions, and for large-scale surveillance.


Assuntos
Babesia/isolamento & purificação , Cabras/parasitologia , Reação em Cadeia da Polimerase Multiplex , Plasmodium/isolamento & purificação , Theileria/isolamento & purificação , Animais , Babesia/genética , Babesia/fisiologia , Bovinos , Plasmodium/genética , Plasmodium/fisiologia , Reprodutibilidade dos Testes , Theileria/genética , Theileria/fisiologia
11.
Parasit Vectors ; 14(1): 247, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33964974

RESUMO

BACKGROUND: Malaria remains a serious public health problem in Cameroon. Implementation of control interventions requires prior knowledge of the local epidemiological situation. Here we report the results of epidemiological and entomological surveys carried out in Tibati, Adamawa Region, Cameroon, an area where malaria transmission is seasonal, 6 years after the introduction of long-lasting insecticidal bed nets. METHODS: Cross-sectional studies were carried out in July 2015 and 2017 in Tibati. Thick blood smears and dried blood spots were collected from asymptomatic and symptomatic individuals in the community and at health centers, respectively, and used for the molecular diagnosis of Plasmodium species. Adult mosquitoes were collected by indoor residual spraying and identified morphologically and molecularly. The infection status of Plasmodium spp. was determined by quantitative PCR, and positivity of PCR-positive samples was confirmed by Sanger sequencing. RESULTS: Overall malaria prevalence in our study population was 55.0% (752/1367) and Plasmodium falciparum was the most prevalent parasite species (94.3%), followed by P. malariae (17.7%) and P. ovale (0.8%); 92 (12.7%) infections were mixed infections. Infection parameters varied according to clinical status (symptomatic/asymptomatic) and age of the sampled population and the collection sites. Infection prevalence was higher in asymptomatic carriers (60.8%), but asexual and sexual parasite densities were lower. Prevalence and intensity of infection decreased with age in both the symptomatic and asymptomatic groups. Heterogeneity in infections was observed at the neighborhood level, revealing hotspots of transmission. Among the 592 Anopheles mosquitoes collected, 212 (35.8%) were An. gambiae, 172 (29.1%) were An. coluzzii and 208 (35.1%) were An. funestus (s.s.). A total of 26 (4.39%) mosquito specimens were infected by Plasmodium sp. and the three Anopheles mosquitoes transmitted Plasmodium at equal efficiency. Surprisingly, we found an An. coluzzii specimen infected by Plasmodium vivax, which confirms circulation of this species in Cameroon. The positivity of all 26 PCR-positive Plasmodium-infected mosquitoes was successively confirmed by sequencing analysis. CONCLUSION: Our study presents the baseline malaria parasite burden in Tibati, Adamawa Region, Cameroon. Our results highlight the high malaria endemicity in the area, and hotspots of disease transmission are identified. Parasitological indices suggest low bednet usage and that implementation of control interventions in the area is needed to reduce malaria burden. We also report for the first time a mosquito vector with naturally acquired P. vivax infection in Cameroon.


Assuntos
Anopheles/efeitos dos fármacos , Anopheles/fisiologia , Inseticidas/farmacologia , Malária/transmissão , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/fisiologia , Adolescente , Adulto , Idoso , Animais , Anopheles/classificação , Anopheles/parasitologia , Camarões/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Malária/epidemiologia , Malária/parasitologia , Masculino , Pessoa de Meia-Idade , Controle de Mosquitos , Mosquitos Vetores/classificação , Mosquitos Vetores/parasitologia , Plasmodium/classificação , Plasmodium/genética , Plasmodium/isolamento & purificação , Plasmodium/fisiologia , Adulto Jovem
12.
J Math Biol ; 82(4): 24, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649976

RESUMO

In this paper, we introduce a reaction-diffusion malaria model which incorporates vector-bias, spatial heterogeneity, sensitive and resistant strains. The main question that we study is the threshold dynamics of the model, in particular, whether the existence of spatial structure would allow two strains to coexist. In order to achieve this goal, we define the basic reproduction number [Formula: see text] and introduce the invasion reproduction number [Formula: see text] for strain [Formula: see text]. A quantitative analysis shows that if [Formula: see text], then disease-free steady state is globally asymptotically stable, while competitive exclusion, where strain i persists and strain j dies out, is a possible outcome when [Formula: see text] [Formula: see text], and a unique solution with two strains coexist to the model is globally asymptotically stable if [Formula: see text], [Formula: see text]. Numerical simulations reinforce these analytical results and demonstrate epidemiological interaction between two strains, discuss the influence of resistant strains and study the effects of vector-bias on the transmission of malaria.


Assuntos
Malária , Modelos Biológicos , Plasmodium , Animais , Número Básico de Reprodução , Simulação por Computador , Humanos , Malária/transmissão , Mosquitos Vetores , Plasmodium/classificação , Plasmodium/fisiologia
13.
Curr Opin Hematol ; 28(3): 158-163, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33631784

RESUMO

PURPOSE OF REVIEW: The current review outlines recent discoveries on the infection of erythroid cells by Plasmodium parasites, focusing on the molecular interactions governing the tropism of parasites for their host cell and the implications of this tropism for parasite biology and erythroid cell maturation. RECENT FINDINGS: Although most studies about the interactions of Plasmodium parasites and their host cell focused on the deadliest human malaria parasite, Plasmodium falciparum, and the erythrocyte, there is increasing evidence that several Plasmodium species, including P. falciparum, also develop within erythroid precursors. These interactions likely modify the remodeling of the host cell by the parasite and affect the maturation of erythroblast and reticulocytes. SUMMARY: A better understanding of the remodeling of immature erythroid cells by Plasmodium parasites will have important implications for the development of antimalarial drugs or vaccines. In addition, deciphering how Plasmodium parasites interfere with erythropoiesis will provide new insights on how these parasites contribute to anemia in malaria patients.


Assuntos
Eritrócitos/parasitologia , Interações Hospedeiro-Parasita , Malária/sangue , Malária/parasitologia , Plasmodium/fisiologia , Animais , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Diferenciação Celular , Eritroblastos/metabolismo , Eritroblastos/parasitologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/imunologia , Eritrócitos/metabolismo , Eritropoese , Interações Hospedeiro-Parasita/imunologia , Humanos , Malária/tratamento farmacológico , Malária/imunologia , Vacinas Antimaláricas/imunologia , Reticulócitos/metabolismo , Reticulócitos/parasitologia
14.
Acta Trop ; 217: 105860, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33587942

RESUMO

Plasmodium relictum is the most common generalist avian malaria parasite, which was reported in over 300 bird species of different orders, particularly often in passerines. This malaria infection is often severe in non-accustomed avian hosts. Currently, five distinct cytochrome b gene lineages have been assigned to P. relictum, with the lineages pSGS1 and pGRW04 being the most common. Based on molecular screenings, the transmission of these two parasite lineages might occur in sympatry, particularly often in sub-Saharan Africa, but they also have been reported to have different areas of transmission globally, with the lineages pSGS1 and pGRW04 being of low (if at all) transmission in huge regions of Americas and Europe, respectively. It remains unclear why these lineages are more often reported in some geographical areas, even though their susceptible vertebrate hosts and vectors are present globally. Co-infections of malaria parasites and other haemosporidians belonging to different species and subgenera are prevalent and even predominate in many bird populations, however, PCR-based protocols using commonly used primers often do not read such co-infections. Because information about the sensitivity of these protocols to read co-infections of the lineages pSGS1 and pGRW04 is absent, this study aimed to unravel this issue experimentally. Blood samples of birds experimentally infected with the single parasite lineages pSGS1 and pGRW04 were used to prepare various combinations of mixes, which were tested by two PCR-based protocols, which have been often used in current avian malaria research. Single infections of the same lineages were used as controls. Careful examination of the sequence electropherograms showed the presence of clear double peaks on polymorphic sites, indicating co-infections. This experiment shows that the broadly used PCR-based protocols can readily distinguish co-infections of these parasite lineages. In other words, the available information about patterns of the geographical distribution of the P. relictum lineages pSGS1 and pGRW04 likely mirrors the existing epidemiological situation but is not a result of the bias due to preferable DNA amplification of one of these lineages during their possible co-infections. This calls for further ecological research aiming determination of factors associated with the transmission of the lineages pSGS1 and pGRW04 in different regions of the globe.


Assuntos
Coinfecção/parasitologia , Internacionalidade , Malária Aviária/parasitologia , Plasmodium/genética , Plasmodium/isolamento & purificação , Reação em Cadeia da Polimerase , Animais , Citocromos b/genética , Filogenia , Plasmodium/fisiologia
15.
Malar J ; 20(1): 82, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568162

RESUMO

BACKGROUND: Avian malaria parasites are microorganisms parasitizing erythrocytes and various tissues of the birds; they are common and distributed worldwide. These parasites are known to infect birds of different taxa and be the cause of the deaths of birds in the wild and in captivity. The species of parasites with the ability to colonize new territories and infect local non-migratory birds are of particular interest. This scenario is likely in temperate zones of Europe, because of climate change and its contribution in spreading vectors of southern origin, which can be involved in the transmission of malaria parasites. In the present study, a tropical Plasmodium parasite from a naturally infected long-distance migrant bird was isolated and tested for its ability to develop in common species of mosquitoes and European short-distance migrant birds. METHODS: Plasmodium sp. (pFANTAIL01) was isolated on the Curonian spit of the Baltic sea coast from the naturally infected Common rosefinch, Carpodacus erythrinus in June 2019. The parasite was described based on the morphological features of its blood stages, the partial mitochondrial cytochrome b gene and development after experimental infection of birds and mosquitoes. The parasite was inoculated into Eurasian siskins, Carduelis spinus. Parasitaemia, haematocrit and weight of birds were monitored. At the end of the survey, internal organs were collected to study exoerythrocytic stages of this parasite. Experimental infection of mosquitoes Culex pipiens form molestus and Culex quinquefasciatus was applied to study sporogonic development of the parasite. RESULTS: Based on morphological features, the parasite was described as a new species, Plasmodium collidatum n. sp., and attributed to subgenus Novyella. It was revealed that the obtained pFANTAIL01 lineage is a generalist parasite infecting a wide range of avian hosts and most likely is transmitted in South and Southeast (SE) Asia and Oceania. In Europe, this strain was recorded only in adult migratory birds wintering in South Asia. This parasite developed high parasitaemia in experimentally infected siskins and caused 25 % mortality. Exoerythrocytic stages of pFANTAIL01 were found in the lungs, liver, spleen and kidney of the deceased birds. Sporogonic development did not occur in Cx. pipiens form molestus and Cx. quinquefasciatus mosquitoes. CONCLUSIONS: Plasmodium collidatum is a highly virulent for Eurasian siskin and completes its development in these birds, which can be considered as a potential vertebrate host if the transmission of the infection starts occurring in Europe and temperate zones.


Assuntos
Doenças das Aves/parasitologia , Culex/parasitologia , Tentilhões , Malária/veterinária , Plasmodium/classificação , Plasmodium/fisiologia , Animais , Europa (Continente) , Feminino , Malária/parasitologia , Masculino , Federação Russa
16.
J Leukoc Biol ; 110(4): 753-769, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33464668

RESUMO

The spleen is a complex secondary lymphoid organ that plays a crucial role in controlling blood-stage infection with Plasmodium parasites. It is tasked with sensing and removing parasitized RBCs, erythropoiesis, the activation and differentiation of adaptive immune cells, and the development of protective immunity, all in the face of an intense inflammatory environment. This paper describes how these processes are regulated following infection and recognizes the gaps in our current knowledge, highlighting recent insights from human infections and mouse models.


Assuntos
Imunidade , Malária/imunologia , Baço/imunologia , Animais , Eritrócitos/parasitologia , Hematopoese , Humanos , Malária/parasitologia , Malária/prevenção & controle , Plasmodium/fisiologia , Baço/parasitologia , Baço/patologia
17.
Tissue Cell ; 69: 101473, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33465520

RESUMO

Malaria, one of the leading causes of death in underdeveloped countries, is primarily diagnosed using microscopy. Computer-aided diagnosis of malaria is a challenging task owing to the fine-grained variability in the appearance of some uninfected and infected class. In this paper, we transform a malaria parasite object detection dataset into a classification dataset, making it the largest malaria classification dataset (63,645 cells), and evaluate the performance of several state-of-the-art deep neural network architectures pretrained on both natural and medical images on this new dataset. We provide detailed insights into the variation of the dataset and qualitative analysis of the results produced by the best models. We also evaluate the models using an independent test set to demonstrate the model's ability to generalize in different domains. Finally, we demonstrate the effect of conditional image synthesis on malaria parasite detection. We provide detailed insights into the influence of synthetic images for the class imbalance problem in the malaria diagnosis context.


Assuntos
Bases de Dados como Assunto , Aprendizado Profundo , Malária/parasitologia , Parasitos/classificação , Algoritmos , Animais , Humanos , Plasmodium/fisiologia
18.
PLoS Pathog ; 17(1): e1009122, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33411818

RESUMO

Lactic acidosis and hyperlactatemia are common metabolic disturbances in patients with severe malaria. Lactic acidosis causes physiological adverse effects, which can aggravate the outcome of malaria. Despite its clear association with mortality in malaria patients, the etiology of lactic acidosis is not completely understood. In this review, the possible contributors to lactic acidosis and hyperlactatemia in patients with malaria are discussed. Both increased lactate production and impaired lactate clearance may play a role in the pathogenesis of lactic acidosis. The increased lactate production is caused by several factors, including the metabolism of intraerythrocytic Plasmodium parasites, aerobic glycolysis by activated immune cells, and an increase in anaerobic glycolysis in hypoxic cells and tissues as a consequence of parasite sequestration and anemia. Impaired hepatic and renal lactate clearance, caused by underlying liver and kidney disease, might further aggravate hyperlactatemia. Multiple factors thus participate in the etiology of lactic acidosis in malaria, and further investigations are required to fully understand their relative contributions and the consequences of this major metabolic disturbance.


Assuntos
Acidose Láctica/etiologia , Malária/complicações , Plasmodium/fisiologia , Acidose Láctica/patologia , Humanos
19.
Parasitol Int ; 80: 102204, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33045411

RESUMO

Human induced changes on landscape can alter the biotic and abiotic factors that influence the transmission of vector-borne parasites. To examine how infection rates of vector-transmitted parasites respond to changes on natural landscapes, we captured 330 Blue-black Grassquits (Volatinia jacarina) in Brazilian biomes and assessed the prevalence and diversity of avian haemosporidian parasites (Plasmodium and Haemoproteus) across avian host populations inhabiting environment under different disturbance and climatic conditions. Overall prevalence in Blue-black Grassquits was low (11%) and infection rates exhibited considerable spatial variation, ranging from zero to 39%. Based on genetic divergence of cytochrome b gene, we found two lineages of Haemoproteus (Parahaemoproteus) and 10 of Plasmodium. We showed that Blue-black Grassquit populations inhabiting sites with higher proportion of native vegetation cover were more infected across Brazil. Other landscape metrics (number of water bodies and distance to urban areas) and climatic condition (temperature and precipitation) known to influence vector activity and promote avian malaria transmission did not explain infection probability in Blue-black Grassquit populations. Moreover, breeding season did not explain prevalence across avian host populations. Our findings suggest that avian haemosporidian prevalence and diversity in Blue-black Grassquit populations are determined by recent anthropogenic changes in vegetation cover that may alter microclimate, thus influencing vector activity and parasite transmission.


Assuntos
Doenças das Aves/epidemiologia , Haemosporida/fisiologia , Infecções Protozoárias em Animais/epidemiologia , Aves Canoras , Animais , Doenças das Aves/parasitologia , Brasil/epidemiologia , Ecossistema , Malária Aviária/epidemiologia , Malária Aviária/parasitologia , Plasmodium/fisiologia , Prevalência , Infecções Protozoárias em Animais/parasitologia
20.
Eur J Med Chem ; 210: 112955, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33131885

RESUMO

Malaria is an endemic disease, prevalent in tropical and subtropical regions which cost half of million deaths annually. The eradication of malaria is one of the global health priority nevertheless, current therapeutic efforts seem to be insufficient due to the emergence of drug resistance towards most of the available drugs, even first-line treatment ACT, unavailability of the vaccine, and lack of drugs with a new mechanism of action. Intensification of antimalarial research in recent years has resulted into the development of single dose multistage therapeutic agents which has advantage of overcoming the antimalarial drug resistance. The present review explored the current progress in the development of new promising antimalarials against prominent target proteins that have the potential to be a clinical candidate. Here, we also reviewed different aspects of drug resistance and highlighted new drug candidates that are currently in a clinical trial or clinical development, along with a few other molecules with excellent antimalarial activity overs ACTs. The summarized scientific value of previous approaches and structural features of antimalarials related to the activity are highlighted that will be helpful for the development of next-generation antimalarials.


Assuntos
Antimaláricos/química , Antimaláricos/farmacologia , Desenvolvimento de Medicamentos , Malária/tratamento farmacológico , Plasmodium/efeitos dos fármacos , Animais , Antimaláricos/uso terapêutico , Resistência a Medicamentos , Humanos , Malária/parasitologia , Terapia de Alvo Molecular , Plasmodium/fisiologia , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/metabolismo , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/uso terapêutico
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