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Malaria Journal Mar 2019While significant advances have been made in understanding Plasmodium falciparum gametocyte biology and its relationship with malaria parasite transmission, the... (Review)
Review
While significant advances have been made in understanding Plasmodium falciparum gametocyte biology and its relationship with malaria parasite transmission, the gametocyte sex ratio contribution to this process still remains a relevant research question. The present review discusses the biology of sex determination in P. falciparum, the underlying host and parasite factors, the sex specific susceptibility to drugs, the effect of sex ratio dynamics on malaria parasite transmission and the development of gametocyte sex specific diagnosis tools. Despite the inherent differences across several studies and approaches, the emerging picture highlights a potentially relevant contribution of the P. falciparum gametocyte sex ratio in the modulation of malaria parasite transmission. The increasing availability of molecular methods to measure gametocyte sex ratio will enable evaluation of important parameters, such as the impact of drug treatment on gametocyte sex ratio in vitro and in vivo as well as the changes of gametocyte sex ratios in natural infections, key steps towards elucidating how these parameters affect parasite infectiousness to the mosquito vectors.
Topics: Disease Transmission, Infectious; Female; Genotype; Humans; Malaria, Falciparum; Male; Phenotype; Plasmodium falciparum
PubMed: 30866941
DOI: 10.1186/s12936-019-2707-0 -
Molecular and Biochemical Parasitology Feb 2011The central role of metabolic perturbation to the pathology of malaria, the promise of antimetabolites as antimalarial drugs and a basic scientific interest in... (Review)
Review
The central role of metabolic perturbation to the pathology of malaria, the promise of antimetabolites as antimalarial drugs and a basic scientific interest in understanding this fascinating example of highly divergent microbial metabolism has spurred a major and concerted research effort towards elucidating the metabolic network of the Plasmodium parasites. Central carbon metabolism, broadly comprising the flow of carbon from nutrients into biomass, has been a particular focus due to clear and early indications that it plays an essential role in this network. Decades of painstaking efforts have significantly clarified our understanding of these pathways of carbon flux, and this foundational knowledge, coupled with the advent of advanced analytical technologies, have set the stage for the development of a holistic, network-level model of plasmodial carbon metabolism. In this review we summarize the current state of knowledge regarding central carbon metabolism and suggest future avenues of research. We focus primarily on the blood stages of Plasmodium falciparum, the most lethal of the human malaria parasites, but also integrate results from simian, avian and rodent models of malaria that were a major focus of early investigations into plasmodial metabolism.
Topics: Carbon; Carbon Cycle; Energy Metabolism; Metabolic Networks and Pathways; Plasmodium
PubMed: 20849882
DOI: 10.1016/j.molbiopara.2010.09.001 -
Briefings in Functional Genomics Sep 2019Malaria parasites are characterized by a complex life cycle that is accompanied by dynamic gene expression patterns. The factors and mechanisms that regulate gene... (Review)
Review
Malaria parasites are characterized by a complex life cycle that is accompanied by dynamic gene expression patterns. The factors and mechanisms that regulate gene expression in these parasites have been searched for even before the advent of next generation sequencing technologies. Functional genomics approaches have substantially boosted this area of research and have yielded significant insights into the interplay between epigenetic, transcriptional and post-transcriptional mechanisms. Recently, considerable progress has been made in identifying sequence-specific transcription factors and DNA-encoded regulatory elements. Here, we review the insights obtained from these efforts including the characterization of core promoters, the involvement of sequence-specific transcription factors in life cycle progression and the mapping of gene regulatory elements. Furthermore, we discuss recent developments in the field of functional genomics and how they might contribute to further characterization of this complex gene regulatory network.
Topics: Gene Expression Regulation; Gene Regulatory Networks; Genomics; Life Cycle Stages; Plasmodium; Promoter Regions, Genetic; Regulatory Elements, Transcriptional; Transcription Factors
PubMed: 31220867
DOI: 10.1093/bfgp/elz004 -
PLoS Neglected Tropical Diseases May 2019A reduction in the global burden of malaria over the past two decades has encouraged efforts for regional malaria elimination. Despite the need to target all Plasmodium...
A reduction in the global burden of malaria over the past two decades has encouraged efforts for regional malaria elimination. Despite the need to target all Plasmodium species, current focus is mainly directed towards Plasmodium falciparum, and to a lesser extent P. vivax. There is a substantial lack of data on both global and local transmission patterns of the neglected malaria parasites P. malariae and P. ovale spp. We used a species-specific real-time PCR assay targeting the Plasmodium 18s rRNA gene to evaluate temporal trends in the prevalence of all human malaria parasites over a 22-year period in a rural village in Tanzania.We tested 2897 blood samples collected in five cross-sectional surveys conducted between 1994 and 2016. Infections with P. falciparum, P. malariae, and P. ovale spp. were detected throughout the study period, while P. vivax was not detected. Between 1994 and 2010, we found a more than 90% reduction in the odds of infection with all detected species. The odds of P. falciparum infection was further reduced in 2016, while the odds of P. malariae and P. ovale spp. infection increased 2- and 6-fold, respectively, compared to 2010. In 2016, non-falciparum species occurred more often as mono-infections. The results demonstrate the persistent transmission of P. ovale spp., and to a lesser extent P. malariae despite a continued decline in P. falciparum transmission. This illustrates that the transmission patterns of the non-falciparum species do not necessarily follow those of P. falciparum, stressing the need for attention towards non-falciparum malaria in Africa. Malaria elimination will require a better understanding of the epidemiology of P. malariae and P. ovale spp. and improved tools for monitoring the transmission of all Plasmodium species, with a particular focus towards identifying asymptomatic carriers of infection and designing appropriate interventions to enhance malaria control.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; DNA, Protozoan; Female; Humans; Infant; Malaria; Male; Middle Aged; Plasmodium falciparum; Plasmodium malariae; Plasmodium ovale; Prevalence; RNA, Ribosomal, 18S; Real-Time Polymerase Chain Reaction; Tanzania; Young Adult
PubMed: 31136585
DOI: 10.1371/journal.pntd.0007414 -
Disease Models & Mechanisms Dec 2019Malaria is an infectious disease caused by parasitic protozoa in the genus. A complete understanding of the biology of these parasites is challenging in view of their... (Review)
Review
Malaria is an infectious disease caused by parasitic protozoa in the genus. A complete understanding of the biology of these parasites is challenging in view of their need to switch between the vertebrate and insect hosts. The parasites are also capable of becoming highly motile and of remaining dormant for decades, depending on the stage of their life cycle. Malaria elimination efforts have been implemented in several endemic countries, but the parasites have proven to be resilient. One of the major obstacles for malaria elimination is the development of antimalarial drug resistance. Ineffective treatment regimens will fail to remove the circulating parasites and to prevent the local transmission of the disease. Genomic epidemiology of malaria parasites has become a powerful tool to track emerging drug-resistant parasite populations almost in real time. Population-scale genomic data are instrumental in tracking the hidden pockets of in nationwide elimination efforts. However, genomic surveillance data can be useful in determining the threat only when combined with a thorough understanding of the malarial resistome - the genetic repertoires responsible for causing and potentiating drug resistance evolution. Even though long-term selection has been a standard method for drug target identification in laboratories, its implementation in large-scale exploration of the druggable space in , along with genome-editing technologies, have enabled mapping of the genetic repertoires that drive drug resistance. This Review presents examples of practical use and describes the latest technology to show the power of real-time genomic epidemiology in achieving malaria elimination.
Topics: Animals; Antimalarials; Culicidae; Disease Eradication; Drug Resistance; Genomics; Humans; International Cooperation; Malaria; Molecular Epidemiology; Mutation; Plasmodium; Plasmodium falciparum
PubMed: 31874839
DOI: 10.1242/dmm.040717 -
Trends in Parasitology May 2013Apicomplexan parasites, including the Plasmodium species that cause malaria, contain three unusual apical secretory organelles (micronemes, rhoptries, and dense... (Review)
Review
Apicomplexan parasites, including the Plasmodium species that cause malaria, contain three unusual apical secretory organelles (micronemes, rhoptries, and dense granules) that are required for the infection of new host cells. Because of their specialized nature, the majority of proteins secreted from these organelles are unique to Apicomplexans and are consequently poorly characterized. Although rhoptry proteins of Plasmodium have been implicated in events central to invasion, there is growing evidence to suggest that proteins originating from this organelle play key roles downstream of parasite entry into the host cell. Here we discuss recent work that has advanced our knowledge of rhoptry protein trafficking and function, and highlight areas of research that require further investigation.
Topics: Animals; Apicomplexa; Host-Parasite Interactions; Organelles; Plasmodium; Protein Transport; Protozoan Proteins
PubMed: 23570755
DOI: 10.1016/j.pt.2013.03.003 -
Malaria Journal Feb 2017Non-human primates (NHPs) as a source for Plasmodium infections in humans are a challenge for malaria elimination. In Brazil, two species of Plasmodium have been...
BACKGROUND
Non-human primates (NHPs) as a source for Plasmodium infections in humans are a challenge for malaria elimination. In Brazil, two species of Plasmodium have been described infecting NHPs, Plasmodium brasilianum and Plasmodium simium. Both species are infective to man. Plasmodium brasilianum resembles morphologically, genetically and immunologically the human quartan Plasmodium malariae. Plasmodium brasilianum naturally infects species of non-human primates from all New World monkey families from a large geographic area. In the family Callitrichidae only the genus Saguinus has been described infected so far. The present study describes the natural infection of P. brasilianum in tamarins and marmosets of the genera Callithrix, Mico and Leontopithecus in the Atlantic forest.
METHODS
One hundred and twenty-two NHPs of the family Callitrichidae housed in the Primate Centre of Rio de Janeiro (CPRJ) were sampled in June 2015, and January and July 2016. The CPRJ is located in the Atlantic forest in the Guapimirim municipality, in the Rio de Janeiro state, where human autochthonous cases of malaria have been reported. The samples were screened for the presence of Plasmodium using optical microscopy and nested PCR for detection of 18S small subunit rRNA gene. The amplicon was sequenced to confirm the molecular diagnosis.
RESULTS
The frequency of Plasmodium infections detected by nested PCR in New World monkeys of the family Callitrichidae was 6.6%. For the first time, Callitrichidae primates of genera Callithrix, Mico and Leontopithecus were found naturally infected with P. brasilianum. Infection was confirmed by sequencing a small fragment of 18S rRNA gene, although no parasites were detected in blood smears.
CONCLUSIONS
The reported P. brasilianum infection in NHP species maintained in captivity suggests that infection can be favoured by the presence of vectors and the proximity between known (and unknown) hosts of malaria. Thus, the list of potential malaria reservoirs needs to be further explored.
Topics: Animals; Brazil; Callitrichinae; DNA, Protozoan; DNA, Ribosomal; Malaria; Microscopy; Plasmodium; Polymerase Chain Reaction; Primate Diseases; RNA, Protozoan; RNA, Ribosomal, 18S; Sequence Analysis, DNA
PubMed: 28187764
DOI: 10.1186/s12936-017-1724-0 -
Frontiers in Cellular and Infection... 2020Malaria remains a serious health concern across the globe. Historically neglected, non- human malarias were put back on the agenda by a paradigm shift in the fight... (Review)
Review
Malaria remains a serious health concern across the globe. Historically neglected, non- human malarias were put back on the agenda by a paradigm shift in the fight against malaria from malaria control to malaria eradication. Here, we review the modeling of the relapsing parasites () and () in non-human primates with a specific focus on the contribution of these models to our current understanding of the factors that govern parasite-host interactions in and parasite biology and pathophysiology.
Topics: Animals; Host-Parasite Interactions; Humans; Malaria; Plasmodium; Plasmodium falciparum; Plasmodium ovale; Plasmodium vivax; Primates
PubMed: 33680982
DOI: 10.3389/fcimb.2020.614122 -
F1000Research 2018Human malaria is a complex disease that can show a wide array of clinical outcomes, from asymptomatic carriage and chronic infection to acute disease presenting various... (Review)
Review
Human malaria is a complex disease that can show a wide array of clinical outcomes, from asymptomatic carriage and chronic infection to acute disease presenting various life-threatening pathologies. The specific outcome of an infection is believed to be determined by a multifactorial interplay between the host and the parasite but with a general trend toward disease attenuation with increasing prior exposure. Therefore, the main burden of malaria in a population can be understood as a function of transmission intensity, which itself is intricately linked to the prevalence of infected hosts and mosquito vectors, the distribution of infection outcomes, and the parasite population diversity. Predicting the long-term impact of malaria intervention measures therefore requires an in-depth understanding of how the parasite causes disease, how this relates to previous exposures, and how different infection pathologies contribute to parasite transmission. Here, we provide a brief overview of recent advances in the molecular epidemiology of clinical malaria and how these might prove to be influential in our fight against this important disease.
Topics: Humans; Malaria; Molecular Epidemiology; Plasmodium
PubMed: 30135713
DOI: 10.12688/f1000research.14991.1 -
Cell Dec 2003The highly A+T rich genomes of human and rodent malarial parasites offer unprecedented glimpses of a lineage that is distinct from other model organisms. Plasmodium is... (Review)
Review
The highly A+T rich genomes of human and rodent malarial parasites offer unprecedented glimpses of a lineage that is distinct from other model organisms. Plasmodium is distinguished by the presence of numerous low complexity inserts within globular domains of proteins. It displays several peculiarities in its transcription apparatus, and its DNA repair system appears to favor a certain innate level of mutability. Plasmodium possesses many cell surface molecules with "animal-like" adhesion modules. Potential genetic footprints of the ancestral eukaryotic algal precursor of the apicoplast are also detectable in its genome.
Topics: Animals; Evolution, Molecular; Genome, Protozoan; Host-Parasite Interactions; Humans; Life Cycle Stages; Phylogeny; Plasmodium; Protein Structure, Tertiary; Protozoan Proteins
PubMed: 14697197
DOI: 10.1016/s0092-8674(03)01023-7