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International Journal For Parasitology.... Apr 2024Target-based approaches have traditionally been used in the search for new anti-infective molecules. Target selection process, a critical step in Drug Discovery,...
Target-based approaches have traditionally been used in the search for new anti-infective molecules. Target selection process, a critical step in Drug Discovery, identifies targets that are essential to establish or maintain the infection, tractable to be susceptible for inhibition, selective towards their human ortholog and amenable for large scale purification and high throughput screening. The work presented herein validates the Plasmodium falciparum mRNA 5' triphosphatase (PfPRT1), the first enzymatic step to cap parasite nuclear mRNAs, as a candidate target for the development of new antimalarial compounds. mRNA capping is essential to maintain the integrity and stability of the messengers, allowing their translation. PfPRT1 has been identified as a member of the tunnel, metal dependent mRNA 5' triphosphatase family which differs structurally and mechanistically from human metal independent mRNA 5' triphosphatase. In the present study the essentiality of PfPRT1 was confirmed and molecular biology tools and methods for target purification, enzymatic assessment and target engagement were developed, with the goal of running a future high throughput screening to discover PfPRT1 inhibitors.
PubMed: 38810336
DOI: 10.1016/j.ijpddr.2024.100537 -
Heliyon May 2024[This corrects the article DOI: 10.1016/j.heliyon.2018.e00612.].
Corrigendum to "Discovery of small molecules through pharmacophore modeling, docking and molecular dynamics simulation against Plasmodium vivax Vivapain-3 (VP-3)" [Heliyon 4(5), May 2018, Article e00612].
[This corrects the article DOI: 10.1016/j.heliyon.2018.e00612.].
PubMed: 38807609
DOI: 10.1016/j.heliyon.2024.e30425 -
Malaria Journal May 2024Deforestation is an important driver of malaria dynamics, with a relevant impact on mosquito ecology, including larval habitat availability, blood-feeding behaviour, and...
BACKGROUND
Deforestation is an important driver of malaria dynamics, with a relevant impact on mosquito ecology, including larval habitat availability, blood-feeding behaviour, and peak biting time. The latter is one of several entomological metrics to evaluate vectorial capacity and effectiveness of disease control. This study aimed to test the effect of forest cover percentage on the peak biting time of Plasmodium-uninfected and infected Nyssorhynchus darlingi females.
METHODS
Mosquitoes were captured utilizing human landing catch (HLC) in the peridomestic habitat in field collections carried out in the wet, wet-dry transition, and dry seasons from 2014 to 2017 in areas with active malaria transmission in Amazonian Brazil. The study locations were in rural settlements in areas with the mean annual malaria parasite incidence (Annual Parasite Incidence, API ≥ 30). All Ny. darlingi females were tested for Plasmodium spp. infection using real time PCR technique. Forest cover percentage was calculated for each collection site using QGIS v. 2.8 and was categorized in three distinct deforestation scenarios: (1) degraded, < 30% forest cover, (2) intermediate, 30-70% forest cover, and (3) preserved, > 70% forest cover.
RESULTS
The highest number of uninfected female Ny. darlingi was found in degraded landscape-sites with forest cover < 30% in any peak biting time between 18:00 and 0:00. Partially degraded landscape-sites, with (30-70%) forest cover, showed the highest number of vivax-infected females, with a peak biting time of 21:00-23:00. The number of P. falciparum-infected mosquitoes was highest in preserved sites with > 70% forest cover, a peak biting at 19:00-20:00, and in sites with 30-70% forest cover at 22:00-23:00.
CONCLUSIONS
Results of this study show empirically that degraded landscapes favour uninfected Ny. darlingi with a peak biting time at dusk (18:00-19:00), whereas partially degraded landscapes affect the behaviour of Plasmodium-infected Ny. darlingi by shifting its peak biting time towards hours after dark (21:00-23:00). In preserved sites, Plasmodium-infected Ny. darlingi bite around dusk (18:00-19:00) and shortly after (19:00-20:00).
Topics: Animals; Brazil; Forests; Female; Feeding Behavior; Mosquito Vectors; Conservation of Natural Resources; Insect Bites and Stings; Seasons; Malaria
PubMed: 38807105
DOI: 10.1186/s12936-024-04984-1 -
Trends in Parasitology May 2024The geographic origin of Plasmodium vivax, a leading cause of human malaria, has been the subject of much speculation. Here we review the evolutionary history of P.... (Review)
Review
The geographic origin of Plasmodium vivax, a leading cause of human malaria, has been the subject of much speculation. Here we review the evolutionary history of P. vivax and P. vivax-like parasites in humans and non-human primates on three continents, providing overwhelming evidence for an African origin. This conclusion is consistent with recent reports showing that Duffy-negative humans in Africa are, in fact, susceptible to P. vivax, with parasites invading Duffy-antigen-expressing erythroid precursors. Thus, the African origin of P. vivax not only explains the distribution of the Duffy-negative genotype but also provides new insight into the history and status of P. vivax malaria in Africa and efforts geared toward its eradication.
PubMed: 38806300
DOI: 10.1016/j.pt.2024.05.001 -
Parasites & Vectors May 2024The spleen plays a critical role in the immune response against malaria parasite infection, where splenic fibroblasts (SFs) are abundantly present and contribute to...
BACKGROUND
The spleen plays a critical role in the immune response against malaria parasite infection, where splenic fibroblasts (SFs) are abundantly present and contribute to immune function by secreting type I collagen (collagen I). The protein family is characterized by Plasmodium vivax tryptophan-rich antigens (PvTRAgs), comprising 40 members. PvTRAg23 has been reported to bind to human SFs (HSFs) and affect collagen I levels. Given the role of type I collagen in splenic immune function, it is important to investigate the functions of the other members within the PvTRAg protein family.
METHODS
Protein structural prediction was conducted utilizing bioinformatics analysis tools and software. A total of 23 PvTRAgs were successfully expressed and purified using an Escherichia coli prokaryotic expression system, and the purified proteins were used for co-culture with HSFs. The collagen I levels and collagen-related signaling pathway protein levels were detected by immunoblotting, and the relative expression levels of inflammatory factors were determined by quantitative real-time PCR.
RESULTS
In silico analysis showed that P. vivax has 40 genes encoding the TRAg family. The C-terminal region of all PvTRAgs is characterized by the presence of a domain rich in tryptophan residues. A total of 23 recombinant PvTRAgs were successfully expressed and purified. Only five PvTRAgs (PvTRAg5, PvTRAg16, PvTRAg23, PvTRAg30, and PvTRAg32) mediated the activation of the NF-κBp65 signaling pathway, which resulted in the production of inflammatory molecules and ultimately a significant reduction in collagen I levels in HSFs.
CONCLUSIONS
Our research contributes to the expansion of knowledge regarding the functional role of PvTRAgs, while it also enhances our understanding of the immune evasion mechanisms utilized by parasites.
Topics: Plasmodium vivax; Fibroblasts; Antigens, Protozoan; Signal Transduction; Animals; Collagen Type I; Spleen; Transcription Factor RelA; Mice; Humans; Malaria, Vivax; Protozoan Proteins; Tryptophan; Escherichia coli; Computational Biology
PubMed: 38802961
DOI: 10.1186/s13071-024-06264-y -
Microorganisms Apr 2024Malaria is one of the most prevalent diseases worldwide with high incidence and mortality. Among the five species that can infect humans, morphologically resembles ,...
Malaria is one of the most prevalent diseases worldwide with high incidence and mortality. Among the five species that can infect humans, morphologically resembles , resulting in misidentification and confusion in diagnosis, and is responsible for malarial disease relapse due to the formation of hypnozoites. receives relatively less attention compared to other major parasites, such as and , primarily due to its lower pathogenicity, mortality rates, and prevalence rates. To efficiently produce lactate dehydrogenase (LDH), a major target for diagnosing malaria, this study used three strains, BL21(DE3), BL21(DE3)pLysS, and Rosetta(DE3), commonly used for recombinant protein production. These strains were characterized to select the optimal strain for LDH (PoLDH) production. Gene cloning for recombinant PoLDH production and transformation of the three strains for protein expression were performed. The optimal PoLDH overexpression and washing buffer conditions in nickel-based affinity chromatography were established to ensure high-purity PoLDH. The yields of PoLDH expressed by the three strains were as follows: BL21(DE3), 7.6 mg/L; BL21(DE3)pLysS, 7.4 mg/L; and Rosetta(DE3), 9.5 mg/L. These findings are expected to be highly useful for PoLDH-specific diagnosis and development of antimalarial therapeutics.
PubMed: 38792706
DOI: 10.3390/microorganisms12050876 -
Tropical Medicine and Infectious Disease May 2024Malaria is a parasitic infection that may result in an acute, life-threatening illness. It is a major public health problem in the tropical world. The disease is caused...
Malaria is a parasitic infection that may result in an acute, life-threatening illness. It is a major public health problem in the tropical world. The disease is caused by the parasites of the genus and is transmitted by female mosquitoes. Saudi Arabia is in the elimination phase of malaria control. Several parts of Saudi Arabia report cases of imported malaria among travelers and visitors. The city of Makkah in Saudi Arabia has a population of about 2.3 million. Moreover, over 6 million religious visitors from different parts of the world visit Makkah annually. During the COVID-19 outbreak, travel restrictions were enforced in Makkah to contain the spread of COVID-19. We compare the total reported cases of malaria in Makkah before, during, and after COVID-19 travel restrictions in this retrospective cross-sectional study. Data on demographics, clinical data, and laboratory parameters were collected from the medical records of the Ministry of Health, Saudi Arabia. The annual malaria incidence rates in Makkah were 29.13/million people (2018), 37.82/million people (2019), 15.65/million people (2020), 12.61/million people (2021), and 48.69/million people (2022). Most of the malaria cases in Makkah were caused by followed by . Sudan, Nigeria, Yamen, Pakistan, and India are the top five countries contributing to malaria cases in Makkah. Weekly malaria case analyses revealed that COVID-19-related travel restrictions resulted in zero malaria cases in Makkah, indicating the magnitude of the travel-related malaria burden in the city.
PubMed: 38787045
DOI: 10.3390/tropicalmed9050112 -
Tropical Medicine and Infectious Disease May 2024Greece has been malaria-free since 1974, after an intense malaria control program. However, as Greece hosts migrant populations from malaria-endemic countries, there is...
Greece has been malaria-free since 1974, after an intense malaria control program. However, as Greece hosts migrant populations from malaria-endemic countries, there is a risk of introducing the disease to specific vulnerable and receptive areas of the country. Knowledge of the genetic diversity of populations is essential for understanding the dynamics of malaria disease transmission in a given region. We used nine highly polymorphic markers to genotype 124 -infected archived DNA samples from human blood specimens referred to the NMRL from all over Greece throughout 2015-2019. The genotypic variability of the samples studied was noted, as they comprised several unique haplotypes, indicative of the importation of a large number of different strains in the country. However, only a few events of local transmission were recorded. Genotyping revealed and confirmed the same clusters as those identified through epidemiological investigation. In only one introduction event was the index case found. No sustained/ongoing malaria transmissions in/between the studied regions or during consecutive years or additional foci of local transmission were observed. Genotyping is an important component in assisting malaria surveillance, as it provides information concerning the patterns of introduction and the effectiveness of implemented malaria control and elimination measures.
PubMed: 38787035
DOI: 10.3390/tropicalmed9050102 -
Tropical Medicine and Infectious Disease Apr 2024The genetic diversity within the circumsporozoite surface protein (PvCSP) of , the predominant malaria species in Thailand, is primarily observed in the northwestern...
The genetic diversity within the circumsporozoite surface protein (PvCSP) of , the predominant malaria species in Thailand, is primarily observed in the northwestern region along the Thailand-Myanmar border. However, as cases shift to southern provinces, particularly Yala Province near the Thailand-Malaysia border, PvCSP diversity remains understudied. Between 2018 and 2020, 89 isolates were collected in Yala Province, a significant malaria hotspot. Employing polymerase chain reaction amplification, restriction fragment length polymorphism (PCR-RFLP), and DNA sequencing, the gene encoding PvCSP () was analyzed. All Yala isolates belonged to the VK210 type, distinct from strains in the western region near the Myanmar border. The central repeat region of revealed two common peptide repeat motifs-GDRADGQPA and GDRAAGQPA-across all southern isolates. Sequence analysis identified two subtypes, with S1 more prevalent (92%) than S2 (8%). This study underscores the limited diversity of VK210 variants of populations in southern Thailand. These baseline findings facilitate monitoring for potential new parasite variants, aiding in the future control and management of in the region.
PubMed: 38787027
DOI: 10.3390/tropicalmed9050094 -
Health Science Reports May 2024Malaria is one of the biggest public health challenges in Ethiopia that has hampered the country's economic growth and development, and the government is on track to...
BACKGROUND
Malaria is one of the biggest public health challenges in Ethiopia that has hampered the country's economic growth and development, and the government is on track to reduce malaria prevalence by 80% by 2025.
OBJECTIVE
As a result, the purpose of this study was to examine the trends in malaria prevalence in Wayu Tuqa District, Gute Health Center, over the last 10 years (2013-2022).
MATERIAL AND METHODS
A retrospective analysis was undertaken to identify the patterns of malaria cases in Wayu Tuqa District, Gute Health Center, from 2013 to 2022 by evaluating the malaria registration laboratory logbook. All socio-demographic data, as well as the year, month, and malaria prevalence, were obtained using a predesigned data collection form from previous years.
RESULTS
In this study, 3402 (22.50%) of the total 15,040 probable patients had malaria. was the most common species, accounting for 82.84% (2818) of the total, followed by (16.00%) (547). Males and people over the age of 15 were the most affected demographics.
CONCLUSION
In this study, the highest number of malaria cases were observed in 2021 and 2022, respectively. Furthermore, the autumn season had the highest incidence of malaria cases, 40% (1339), while the spring season had the lowest prevalence, 16% (546). The general trend of plasmodium species at Gute Health Center over the previous 10 years (2013-2022) has not shown inconsistent trends. As a result, proper malaria prevention and control planning, implementation, and monitoring should be strengthened at all levels.
PubMed: 38784252
DOI: 10.1002/hsr2.2156