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drug resistance

NOT Open Access | Diagnosing the drug resistance signature in Plasmodium falciparum: a review from contemporary methods to novel approaches

September 8, 2021 - 15:58 -- NOT Open Access
Author(s): 
Murmu LK, Sahu AA, Barik TK
Reference: 
J Parasit Dis. 2021 Sep;45(3):869-876


The genome sequence project of the human malaria parasite Plasmodium falciparum reveal variations in the parasite DNA sequence. Most of these variations are single nucleotide polymorphism (SNP). A high frequency of single nucleotide polymorphism (SNP) in the Plasmodium falciparum population is usually a benchmark for anti-malarial resistance which allows parasites to be elusive to the chemotherapeutic agents, vaccine and vector control strategies, resulting in the leading cause of morbidity and mortality globally.

Genetic surveillance in the Greater Mekong subregion and South Asia to support malaria control and elimination

August 10, 2021 - 18:10 -- Open Access
Author(s): 
Jacob CG, Thuy-Nhien N, Miotto O, et al.
Reference: 
Elife. 2021 Aug 10;10:e62997

National Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures.

Connected diagnostics to improve accurate diagnosis, treatment, and conditional payment of malaria services in Kenya

August 10, 2021 - 17:58 -- Open Access
Author(s): 
van Duijn SMC, Siteyi AK, Rinke de Wit TF, et al.
Reference: 
BMC Med Inform Decis Mak. 2021 Aug 4;21(1):233

In sub-Saharan Africa, the material and human capacity to diagnose patients reporting with fever to healthcare providers is largely insufficient. Febrile patients are typically treated presumptively with antimalarials and/or antibiotics. Such over-prescription can lead to drug resistance and involves unnecessary costs to the health system. International funding for malaria is currently not sufficient to control malaria. Transition to domestic funding is challenged by UHC efforts and recent COVID-19 outbreak. Herewith we present a digital approach to improve efficiencies in diagnosis and treatment of malaria in endemic Kisumu, Kenya: Connected Diagnostics. The objective of this study is to evaluate the feasibility, user experience and clinical performance of this approach in Kisumu.

Inhibitory compounds targeting Plasmodium falciparum Gyrase B

August 4, 2021 - 16:02 -- Open Access
Author(s): 
Pakosz Z, Lin TY, Michalczyk E, Nagano S, Heddle JG
Reference: 
Antimicrob Agents Chemother. 2021 Aug 2:AAC0026721.

Malaria persists as a major health problem due to the spread of drug resistance and the lack of effective vaccines. DNA gyrase is a well-validated and extremely effective therapeutic target in bacteria, and it is also known to be present in the apicoplast of malarial species including Plasmodium falciparum. This raises the possibility that it could be a useful target for novel antimalarials.

NOT Open Access | Evaluation of ethnopharmacologically selected Vitex negundo L. for In vitro antimalarial activity and secondary metabolite profiling

July 20, 2021 - 13:31 -- NOT Open Access
Author(s): 
Dwivedi MK, Shukla R, Sharma NK, Manhas A, Srivastava K, Kumar N, Singh PK
Reference: 
J Ethnopharmacol. 2021 Jul 15;275:114076

Limited drugs, rise in drug resistance against frontline anti-malarial drugs, non-availability of efficacious vaccines and high cost of drug development hinders malaria intervention programs. Search for safe, effective and affordable plant based anti-malarial agents, thus becomes crucial and vital in the current scenario. The Vitex negundo L. is medicinal plant possessing a variety of pharmaceutically important compounds. The plant is used traditionally worldwide for the treatment of malaria including India and Malaysia by the indigenous tribes. In vitro studies have reported the anti-malarial use of the plant in traditional medicinal systems.

Mapping partner drug resistance to guide antimalarial combination therapy policies in sub-Saharan Africa

July 20, 2021 - 13:11 -- Open Access
Author(s): 
Ehrlich HY, Bei AK, Weinberger DM, Warren JL, Parikh S
Reference: 
Proc Natl Acad Sci U S A. 2021 Jul 20;118(29):e2100685118

Resistance to artemisinin-based combination therapies (ACTs) threatens the global control of Plasmodium falciparum malaria. ACTs combine artemisinin-derived compounds with partner drugs to enable multiple mechanisms of clearance. Although ACTs remain widely effective in sub-Saharan Africa, long-standing circulation of parasite alleles associated with reduced partner drug susceptibility may contribute to the development of clinical resistance.

Immune selection suppresses the emergence of drug resistance in malaria parasites but facilitates its spread

July 20, 2021 - 12:43 -- Open Access
Author(s): 
Whitlock AOB, Juliano JJ, Mideo N
Reference: 
PLoS Comput Biol. 2021 Jul 19;17(7):e1008577

Although drug resistance in Plasmodium falciparum typically evolves in regions of low transmission, resistance spreads readily following introduction to regions with a heavier disease burden. This suggests that the origin and the spread of resistance are governed by different processes, and that high transmission intensity specifically impedes the origin. Factors associated with high transmission, such as highly immune hosts and competition within genetically diverse infections, are associated with suppression of resistant lineages within hosts.

NOT Open Access | Asymptomatic malaria infection prevailing risks for human health and malaria elimination

July 6, 2021 - 14:54 -- NOT Open Access
Author(s): 
Prusty D, Gupta N, Upadhyay A, Dar A, Naik B, Kumar N, Prajapati VK
Reference: 
Infect Genet Evol. 2021 Jun 30:104987

There has been a consistent rise in malaria cases in the last few years. The existing malaria control measures are challenged by insecticide resistance in the mosquito vector, drug résistance in parasite populations, and asymptomatic malaria (ASM) in healthy individuals. The absence of apparent malaria symptoms and the presence of low parasitemia makes ASM a hidden reservoir for malaria transmission and an impediment in malaria elimination efforts.

Plasmodium falciparum kelch 13 Mutations, 9 Countries in Africa, 2014-2018

July 6, 2021 - 13:16 -- Open Access
Author(s): 
Schmedes SE, Patel D, Talundzic E, et al.
Reference: 
Emerg Infect Dis. 2021 Jul;27(7):1902-1908

The spread of drug resistance to antimalarial treatments poses a serious public health risk globally. To combat this risk, molecular surveillance of drug resistance is imperative. We report the prevalence of mutations in the Plasmodium falciparum kelch 13 propeller domain associated with partial artemisinin resistance, which we determined by using Sanger sequencing samples from patients enrolled in therapeutic efficacy studies from 9 sub-Saharan countries during 2014-2018.

NOT Open Access | Computational prediction of the effects of non-synonymous single nucleotide polymorphisms on the GPI-anchor transamidase subunit GPI8p of Plasmodium falciparum

June 9, 2021 - 14:57 -- NOT Open Access
Author(s): 
Singh SK, Reddy MS
Reference: 
Comput Biol Chem. 2021 Jun;92:107461

Drug resistance is increasingly evolving in malaria parasites; hence, it is important to discover and establish alternative drug targets. In this context, GPI-anchor transamidase (GPI-T) is a potential drug target primarily of its crucial role in the development and survival of the parasite in the GPI anchor biosynthesis pathway. The present investigation was undertaken to explore the plausible effects of nsSNP on the structure and functions of GPI-T subunit GPI8p of Plasmodium falciparum.

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