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Scientific Articles

Understanding the Pyrimethamine Drug Resistance Mechanism via Combined Molecular Dynamics and Dynamic Residue Network Analysis

February 25, 2020 - 16:31 -- Open Access
Author(s): 
Amusengeri A, Tata RB, Tastan Bishop Ö
Reference: 
Molecules 2020, 25(4), 904

In this era of precision medicine, insights into the resistance mechanism of drugs are integral for the development of potent therapeutics. Here, we sought to understand the contribution of four point mutations (N51I, C59R, S108N, and I164L) within the active site of the malaria parasite enzyme dihydrofolate reductase (DHFR) towards the resistance of the antimalarial drug pyrimethamine. Homology modeling was used to obtain full-length models of wild type (WT) and mutant DHFR.

Assessment of environmental variability on malaria transmission in a malaria-endemic rural dry zone locality of Sri Lanka: The wavelet approach

February 25, 2020 - 16:28 -- Open Access
Author(s): 
Mahendran R, Pathirana S, Piyatilake ITS, Perera SSN, Weerasinghe MC
Reference: 
PLoS ONE 15(2): e0228540

Malaria is a global public health concern and its dynamic transmission is still a complex process. Malaria transmission largely depends on various factors, including demography, geography, vector dynamics, parasite reservoir, and climate. The dynamic behaviour of malaria transmission has been explained using various statistical and mathematical methods. Of them, wavelet analysis is a powerful mathematical technique used in analysing rapidly changing time-series to understand disease processes in a more holistic way.

Field assessment of 4-hydroxycoumarin as an attractant for anthropophilic Anopheles spp. vectors of malaria in Madagascar

February 25, 2020 - 16:27 -- Open Access
Author(s): 
Andrianjafy TM, Ramanandraibe VV, Andrianarijaona ET, Ramarosandratana NH, Ravaomanarivo LH, Mavingui P, Lemaire M
Reference: 
Sci Rep. 2020 Feb 20;10(1):3048

Mosquito-borne diseases like malaria are a major public health problem in tropical countries, such as Madagascar. Female Anopheles mosquito vectors the human malaria parasites (Plasmodium spp.) and is important indicator in malaria surveillance activities. Among the various means of vector control in Madagascar, the use of attractants for mass trapping of target species could be an alternative to insecticides.

Molecular evidence of sustained urban malaria transmission in Amazonian Brazil, 2014-2015

February 25, 2020 - 16:25 -- Open Access
Author(s): 
Salla LC, Rodrigues PT, Corder RM, Johansen IC, Ladeia-Andrade S, Ferreira MU
Reference: 
Epidemiol Infect. 2020 Feb 21:1-22

The relative contribution of imported vs.locally acquired infections to urban malaria burden remains largely unexplored in Latin America, the most urbanisedregion in the developing world. Here we use a simple molecular epidemiology framework to examine the transmission dynamics of Plasmodium vivax in Mâncio Lima, the Amazonian municipality with the highest malaria incidence rate in Brazil.

NOT Open Access | The cryptic unstable transcripts are associated with developmentally regulated gene expression in blood-stage Plasmodium falciparum

February 25, 2020 - 16:24 -- NOT Open Access
Author(s): 
Yin S, Fan Y, He X, Wei G, Wen Y, Zhao Y, Shi M, Wei J, Chen H, Han J, Jiang L, Zhang Q
Reference: 
RNA Biol. 2020 Feb 20

The tight gene expression regulation controls the development and pathogenesis of human malaria parasites Plasmodium falciparum throughout the complex life cycle. Recent studies have revealed the pervasive nascent transcripts in the genome of P. falciparum, suggesting the existence of a hidden transcriptome involved in the dynamic gene expression. However, the landscape and related biological functions of nascent non-coding RNAs (ns-ncRNAs) are still poorly explored.

NOT Open Access | Probing the Open Global Health Chemical Diversity Library for multistage-active starting points for next-generation antimalarials

February 25, 2020 - 16:23 -- NOT Open Access
Author(s): 
Abraham M, Gagaring K, Winzeler EA, et al.
Reference: 
ACS Infect Dis. 2020 Feb 20

 

Most phenotypic screens aiming to discover new antimalarial chemotypes begin with low cost, high-throughput tests against the asexual blood stage (ABS) of the malaria parasite lifecycle. Compounds active against the ABS are then sequentially tested in more difficult assays that predict whether a compound has other beneficial attributes. Although applying this strategy to new chemical libraries may yield new leads, repeated iterations may lead to diminishing returns and the rediscovery of chemotypes hitting well-known targets.

The enigmatic mechanisms by which Plasmodium vivax infects Duffy-negative individuals

February 25, 2020 - 16:22 -- Open Access
Author(s): 
Popovici J, Roesch C, Rougeron V
Reference: 
PLoS Pathog 16(2): e1008258

The absence of the Duffy protein at the surface of erythrocytes was considered for decades to confer full protection against Plasmodium vivax as this blood group is the receptor for the key parasite ligand P. vivax Duffy binding protein (PvDBP). However, it is now clear that the parasite is able to break through this protection and induce clinical malaria in Duffy-negative people, although the underlying mechanisms are still not understood.

NOT Open Access | From a basic to a functional approach for developing a blood stage vaccine against Plasmodium vivax

February 25, 2020 - 16:19 -- NOT Open Access
Author(s): 
Patarroyo MA, Arévalo-Pinzón G, Moreno-Pérez DA
Reference: 
Expert Rev Vaccines. 2020 Feb 20

Numerous challenges have hampered developing an anti-malarial vaccine against the most widespread malarial parasite worldwide: Plasmodium vivax. Despite the progress achieved in studying proteins in short-term in vitro culture or in experimental models, there is still no clear method for defining which antigens or their regions should be prioritised for including them in a vaccine.

Plasma parasitemia as assessed by quantitative PCR in relation to clinical disease severity in African adults with falciparum malaria with and without HIV co-infection

February 25, 2020 - 16:17 -- Open Access
Author(s): 
Berg A, Patel S, Tellevik MG, Haanshuus CG, Dalen I, Otterdal K, Ueland T, Moyo SJ, Aukrust P, Langeland N
Reference: 
Infection. 2020 Feb 19

When considering malaria disease severity, estimation of parasitemia in erythrocytes is important, but sometimes misleading, since the infected erythrocytes may be sequestered in peripheral capillaries. In African children and Asian adults with falciparum malaria, parasitemia as assessed by quantitative PCR (qPCR) in plasma seems to be a valuable indicator of disease severity, but data on African adults as well as the impact of co-infection with HIV is lacking.

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