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Virulence Dec 2023Infections with and cause over 600,000 deaths each year, concentrated in Africa and in young children, but much of the world's population remain at risk of infection.... (Review)
Review
Infections with and cause over 600,000 deaths each year, concentrated in Africa and in young children, but much of the world's population remain at risk of infection. In this article, we review the latest developments in the immunogenicity and pathogenesis of malaria, with a particular focus on , the leading malaria killer. Pathogenic factors include parasite-derived toxins and variant surface antigens on infected erythrocytes that mediate sequestration in the deep vasculature. Host response to parasite toxins and to variant antigens is an important determinant of disease severity. Understanding how parasites sequester, and how antibody to variant antigens could prevent sequestration, may lead to new approaches to treat and prevent disease. Difficulties in malaria diagnosis, drug resistance, and specific challenges of treating pose challenges to malaria elimination, but vaccines and other preventive strategies may offer improved disease control.
Topics: Child; Humans; Child, Preschool; Virulence; Malaria; Malaria, Falciparum; Plasmodium falciparum; Plasmodium vivax; Protozoan Proteins
PubMed: 36419237
DOI: 10.1080/21505594.2022.2150456 -
Parasitology International Oct 2021An estimated 229 million cases of malaria occurred worldwide in 2019. Both, Plasmodium falciparum and P. vivax are responsible for most of the malaria disease burden in... (Review)
Review
An estimated 229 million cases of malaria occurred worldwide in 2019. Both, Plasmodium falciparum and P. vivax are responsible for most of the malaria disease burden in the world. Despite difficulties in obtaining an accurate number, the global estimates of cases in 2019 are approximately 229 million of which 2.8% are due to P. vivax, and the total number of malaria deaths are approximately 409 million. Regional elimination or global eradication of malaria will be a difficult task, particularly for P. vivax due to the particular biological features related to the hypnozoite, leading to relapse. Countries that have shown successful episodes of a decrease in P. falciparum malaria, are left with remaining P. vivax malaria cases. This is caused by the mechanism that the parasite has evolved to remain dormant in the liver forming hypnozoites. Furthermore, while clinical trials of vaccines against P. falciparum are making fast progress, a very different picture is seen with P. vivax, where only few candidates are currently active in clinical trials. We discuss the challenge that represent the hypnozoite for P. vivax vaccine development, the potential of Controlled Human Malaria Challenges (CHMI) and the leading vaccine candidates assessed in clinical trials.
Topics: Animals; Humans; Malaria Vaccines; Malaria, Vivax; Plasmodium vivax
PubMed: 34166786
DOI: 10.1016/j.parint.2021.102411 -
Parasitology International Apr 2022Malaria elimination means cessation of parasite transmission. At present, the declining malaria incidence in many countries has made elimination a feasible goal....
Malaria elimination means cessation of parasite transmission. At present, the declining malaria incidence in many countries has made elimination a feasible goal. Transmission control has thus been placed at the center of the national malaria control programs. The efficient transmission of Plasmodium vivax from humans to mosquitoes is a key factor that helps perpetuate malaria in endemic areas. A better understanding of transmission is crucial to the success of elimination efforts. Biological delineation of the parasite transmission process is important for identifying and prioritizing new targets of intervention. Identification of the infectious parasite reservoir in the community is key to devising an effective elimination strategy. Here we describe the fundamental characteristics of P. vivax gametocytes - the dynamics of their production, longevity, and the relationship with the total parasitemia - as well as recent advances in the molecular understanding of parasite sexual development. In relation to malaria elimination, factors influencing the human infectivity and the current evidence for a role of asymptomatic carriers in transmission are presented.
Topics: Animals; Anopheles; Female; Humans; Malaria, Vivax; Male; Mosquito Vectors; Parasitemia; Plasmodium vivax
PubMed: 34748969
DOI: 10.1016/j.parint.2021.102497 -
Trends in Parasitology Oct 2022The ability of the intraerythrocytic Plasmodium spp. to form spontaneous rosettes with uninfected red blood cells (URBCs) has been observed in the medically important... (Review)
Review
The ability of the intraerythrocytic Plasmodium spp. to form spontaneous rosettes with uninfected red blood cells (URBCs) has been observed in the medically important malaria parasites. Since the discovery of rosettes in the late 1980s, different formation mechanisms and pathobiological roles have been postulated for rosetting; most of which have focused on Plasmodium falciparum. Recent breakthroughs, including new data from Plasmodium vivax, have highlighted the multifaceted roles of rosetting in the immunopathobiology and the development of drug resistance in human malaria. Here, we provide new perspectives on the formation and the role of rosetting in malaria rheopathobiology.
Topics: Cell Adhesion; Erythrocytes; Humans; Malaria; Malaria, Falciparum; Plasmodium falciparum; Plasmodium vivax; Rosette Formation
PubMed: 36031553
DOI: 10.1016/j.pt.2022.08.001 -
Experimental Biology and Medicine... Oct 2023Malaria is the leading human parasitosis and is transmitted through the bite of anopheline mosquitoes infected with parasites of the genus spp. Among the seven species... (Review)
Review
Malaria is the leading human parasitosis and is transmitted through the bite of anopheline mosquitoes infected with parasites of the genus spp. Among the seven species that cause malaria in humans, is the most prevalent species in Latin America. In recent years, there have been an increasing number of reports of clinical complications caused by infections, which were previously neglected and underestimated. biology remains with large gaps. The emergence of next-generation sequencing technology has ensured a breakthrough in species knowledge. Coupled with this, the deposition of the Sal-1 reference genome allowed an increase in transcriptomics projects by accessing messenger RNA. Thus, the regulation of differential gene expression according to the parasite life stage was verified, and several expressed genes were linked to different biological functions. Today, with the progress associated with RNA sequencing technologies, it is possible to detect nuances and obtain robust results. Discoveries provided by transcriptomic studies allow us to understand topics such as RNA expression and regulation and proteins and metabolic pathways involved during different stages of the parasite life cycle. The information obtained enables a better comprehension of immune system evasion mechanisms; invasion and adhesion strategies used by the parasite; as well as new vaccine targets, potential molecular markers, and others therapeutic targets. In this review, we provide new insights into biology by summarizing recent findings in transcriptomic studies.
Topics: Animals; Humans; Plasmodium vivax; Malaria, Vivax; Malaria; Parasites; Gene Expression Profiling
PubMed: 37786955
DOI: 10.1177/15353702231198070 -
Parasitology International Apr 2022Existing control measures have significantly reduced malaria morbidity and mortality in the last two decades, although these reductions are now stalling. Significant... (Review)
Review
Existing control measures have significantly reduced malaria morbidity and mortality in the last two decades, although these reductions are now stalling. Significant efforts have been undertaken to develop malaria vaccines. Recently, extensive progress in malaria vaccine development has been made for Plasmodium falciparum. To date, only the RTS,S/AS01 vaccine has been tested in Phase 3 clinical trials and is now under implementation, despite modest efficacy. Therefore, the development of a malaria transmission-blocking vaccine (TBV) will be essential for malaria elimination. Only a limited number of TBVs have reached pre-clinical or clinical development with several major challenges impeding their development, including low immunogenicity in humans. TBV development efforts against P. vivax, the second major cause of malaria morbidity, lag far behind those for P. falciparum. In this review we summarize the latest progress, challenges and innovations in P. vivax TBV research and discuss how to accelerate its development.
Topics: Humans; Malaria Vaccines; Malaria, Falciparum; Malaria, Vivax; Plasmodium falciparum; Plasmodium vivax; Vaccine Development
PubMed: 34896614
DOI: 10.1016/j.parint.2021.102525 -
Malaria Journal Nov 2022This review article aims to investigate the genotypic profiles of Plasmodium falciparum and Plasmodium vivax isolates collected across a wide geographic region and their... (Review)
Review
This review article aims to investigate the genotypic profiles of Plasmodium falciparum and Plasmodium vivax isolates collected across a wide geographic region and their association with resistance to anti-malarial drugs used in Indonesia. A systematic review was conducted between 1991 and date. Search engines, such as PubMed, Science Direct, and Google Scholar, were used for articles published in English and Indonesian to search the literature. Of the 471 initially identified studies, 61 were selected for 4316 P. falciparum and 1950 P. vivax individual infections. The studies included 23 molecular studies and 38 therapeutic efficacy studies. K76T was the most common pfcrt mutation. K76N (2.1%) was associated with the haplotype CVMNN. By following dihydroartemisinin-piperaquine (DHA-PPQ) therapy, the mutant pfmdr1 alleles 86Y and 1034C were selected. Low prevalence of haplotype N86Y/Y184/D1246Y pfmdr1 reduces susceptibility to AS-AQ. SNP mutation pvmdr1 Y976F reached 96.1% in Papua and East Nusa Tenggara. Polymorphism analysis in the pfdhfr gene revealed 94/111 (84.7%) double mutants S108N/C59R or S108T/A16V in Central Java. The predominant pfdhfr haplotypes (based on alleles 16, 51, 59,108, 164) found in Indonesia were ANCNI, ANCSI, ANRNI, and ANRNL. Some isolates carried A437G (35.3%) or A437G/K540E SNPs (26.5%) in pfdhps. Two novel pfdhps mutant alleles, I588F/G and K540T, were associated with six pfdhps haplotypes. The highest prevalence of pvdhfr quadruple mutation (F57L/S58R/T61M/S117T) (61.8%) was detected in Papua. In pvdhps, the only polymorphism before and after 2008 was 383G mutation with 19% prevalence. There were no mutations in the pfk13 gene reported with validated and candidate or associated k13 mutation. An increased copy number of pfpm2, associated with piperaquine resistance, was found only in cases of reinfection. Meanwhile, mutation of pvk12 and pvpm4 I165V is unlikely associated with ART and PPQ drug resistance. DHA-PPQ is still effective in treating uncomplicated falciparum and vivax malaria. Serious consideration should be given to interrupt local malaria transmission and dynamic patterns of resistance to anti-malarial drugs to modify chemotherapeutic policy treatment strategies. The presence of several changes in pfk13 in the parasite population is of concern and highlights the importance of further evaluation of parasitic ART susceptibility in Indonesia.
Topics: Plasmodium vivax; Plasmodium falciparum; Indonesia; Antimalarials; Artemisinins; Polymorphism, Single Nucleotide; Drug Resistance
PubMed: 36443817
DOI: 10.1186/s12936-022-04385-2 -
Science Translational Medicine Jul 2023There are no licensed vaccines against . We conducted two phase 1/2a clinical trials to assess two vaccines targeting Duffy-binding protein region II (PvDBPII)....
There are no licensed vaccines against . We conducted two phase 1/2a clinical trials to assess two vaccines targeting Duffy-binding protein region II (PvDBPII). Recombinant viral vaccines using chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) vectors as well as a protein and adjuvant formulation (PvDBPII/Matrix-M) were tested in both a standard and a delayed dosing regimen. Volunteers underwent controlled human malaria infection (CHMI) after their last vaccination, alongside unvaccinated controls. Efficacy was assessed by comparisons of parasite multiplication rates in the blood. PvDBPII/Matrix-M, given in a delayed dosing regimen, elicited the highest antibody responses and reduced the mean parasite multiplication rate after CHMI by 51% ( = 6) compared with unvaccinated controls ( = 13), whereas no other vaccine or regimen affected parasite growth. Both viral-vectored and protein vaccines were well tolerated and elicited expected, short-lived adverse events. Together, these results support further clinical evaluation of the PvDBPII/Matrix-M vaccine.
Topics: Humans; Animals; Parasites; Plasmodium vivax; Vaccination; Malaria
PubMed: 37437014
DOI: 10.1126/scitranslmed.adf1782 -
Malaria Journal May 2022Malaria is a vector-borne disease caused by protozoan parasites of the genus Plasmodium. Plasmodium vivax is the most prevalent human-infecting species in the Americas.... (Review)
Review
Malaria is a vector-borne disease caused by protozoan parasites of the genus Plasmodium. Plasmodium vivax is the most prevalent human-infecting species in the Americas. However, the origins of this parasite in this continent are still debated. Similarly, it is now accepted that the existence of Plasmodium simium is explained by a P. vivax transfer from humans to monkey in America. However, many uncertainties still exist concerning the origin of the transfer and whether several transfers occurred. In this review, the most recent studies that addressed these questions using genetic and genomic approaches are presented.
Topics: Biological Evolution; Genome; Humans; Malaria; Plasmodium; Plasmodium vivax
PubMed: 35505431
DOI: 10.1186/s12936-022-04132-7 -
Frontiers in Cellular and Infection... 2021The development of genetic manipulation of in the 1980s was key to study malaria biology. Genetically modified parasites have been used to study several aspects of the... (Review)
Review
The development of genetic manipulation of in the 1980s was key to study malaria biology. Genetically modified parasites have been used to study several aspects of the disease, such as red blood cell invasion, drug resistance mechanisms, gametocyte development and mosquito transmission. However, biological and genetic differences between and the other human malaria parasites make a poor model to study different species. The lack of robust systems of long-term culture of and the other human malaria parasites lagged the genetic manipulation of these species. Here we review the efforts to generate genetically modified non- human malaria parasites, and . Using models - infection of non-human primates such as rhesus macaques and saimiri monkeys - researchers were able to generate transgenic lines of , and . The development of long-term culture of in the 2000's, using rhesus and human red blood cells, created a platform to genetically manipulate non- malaria parasites. Recently, the use of CRISPR/Cas9 technology to genome edit provides another tool to non-falciparum malaria research, extending the possibilities and allowing researchers to study different aspects of the biology of these parasites and understand the differences between these species and .
Topics: Animals; Humans; Macaca mulatta; Malaria; Malaria, Vivax; Parasites; Plasmodium knowlesi; Plasmodium vivax
PubMed: 34527600
DOI: 10.3389/fcimb.2021.680460