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drug resistance

Functional characterization of 5′ UTR cis-acting sequence elements that modulate translational efficiency in Plasmodium falciparum and humans

January 19, 2022 - 20:42 -- Open Access
Valentina E. Garcia, Rebekah Dial and Joseph L. DeRisi
Malaria Journal 2022 21:15, 6 January 2022

The eukaryotic parasite Plasmodium falciparum causes millions of malarial infections annually while drug resistance to common anti-malarials is further confounding eradication efforts. Translation is an attractive therapeutic target that will benefit from a deeper mechanistic understanding. As the rate limiting step of translation, initiation is a primary driver of translational efficiency. It is a complex process regulated by both cis and trans acting factors, providing numerous potential targets. Relative to model organisms and humans, P. falciparum mRNAs feature unusual 5′ untranslated regions suggesting cis-acting sequence complexity in this parasite may act to tune levels of protein synthesis through their effects on translational efficiency.

Molecular identification and anti-malarial drug resistance profile of Plasmodium falciparum from patients attending Kisoro Hospital, southwestern Uganda

January 18, 2022 - 21:17 -- Open Access
Manirakiza G, Kassaza K, Taremwa IM, Bazira J, Byarugaba F
Malar J. 2022 Jan 15;21(1):21

The evolution of malaria infection has necessitated the development of highly sensitive diagnostic assays, as well as the use of dried blood spots (DBS) as a potential source of deoxyribonucleic acid (DNA) yield for polymerase chain reaction (PCR) assays. This study identified the different Plasmodium species in malaria-positive patients, and the anti-malarial drug resistance profile for Plasmodium falciparum using DBS samples collected from patients attending Kisoro Hospital in Kisoro district, Southwestern Uganda.

Evaluation of a parasite-density based pooled targeted amplicon deep sequencing (TADS) method for molecular surveillance of Plasmodium falciparum drug resistance genes in Haiti

January 18, 2022 - 21:03 -- Open Access
Louha S, Herman C, Talundzic E, et al.
PLoS One. 2022 Jan 14;17(1):e0262616

Sequencing large numbers of individual samples is often needed for countrywide antimalarial drug resistance surveillance. Pooling DNA from several individual samples is an alternative cost and time saving approach for providing allele frequency (AF) estimates at a population level. Using 100 individual patient DNA samples of dried blood spots from a 2017 nationwide drug resistance surveillance study in Haiti, we compared codon coverage of drug resistance-conferring mutations in four Plasmodium falciparum genes (crt, dhps, dhfr, and mdr1), for the same deep sequenced samples run individually and pooled.

Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria and prevalence of molecular markers associated with artemisinin and partner drug resistance in Uganda

January 12, 2022 - 23:28 -- Open Access
Chris Ebong, Asadu Sserwanga, Adoke Yeka, et al.
Malaria Journal 2021 20:484, 24 December 2021

In Uganda, artemether-lumefantrine (AL) is first-line therapy and dihydroartemisinin-piperaquine (DP) second-line therapy for the treatment of uncomplicated malaria. This study evaluated the efficacy and safety of AL and DP in the management of uncomplicated falciparum malaria and measured the prevalence of molecular markers of resistance in three sentinel sites in Uganda from 2018 to 2019.

Not Open Access | In-Silico Design, Chemical Synthesis and Biological Screening of Novel 4-(1H)-Pyridone-based Antimalarial Agents

December 7, 2021 - 21:31 -- NOT Open Access
Audu O, Stander A, Ajani O, Egieyeh S, October N
Chem Biol Drug Des. 2021 Nov 30

Identifying novel lead compounds in drug discovery has been challenging because of the rapid rise of drug resistance to the existing chemotherapeutics and a lack of understanding of complex metabolic pathways in the parasite. Integrating computational and experimental approaches has shown to be of great worth in identifying and developing novel promising pharmacophore hybrids.

Malaria Trigram: improving the visualization of recurrence data for malaria elimination

November 20, 2021 - 14:08 -- Open Access
Cleber Matos de Morais, Kayo Henrique de Carvalho Monteiro, Jose Diego Brito-Sousa, Wuelton Marcelo Monteiro, Vanderson Souza Sampaio, Patricia Takako Endo and Judith Kelner
Malaria Journal 2021 20:431, 30 October 2021

Although considerable success in reducing the incidence of malaria has been achieved in Brazil in recent years, an increase in the proportion of cases caused by the harder-to-eliminate Plasmodium vivax parasite can be noted. Recurrences in P. vivax malaria cases are due to new mosquito-bite infections, drug resistance or especially from relapses arising from hypnozoites. As such, new innovative surveillance strategies are needed. The aim of this study was to develop an infographic visualization tool to improve individual-level malaria surveillance focused on malaria elimination in the Brazilian Amazon.

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
Murmu LK, Sahu AA, Barik TK
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
Jacob CG, Thuy-Nhien N, Miotto O, et al.
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
van Duijn SMC, Siteyi AK, Rinke de Wit TF, et al.
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.


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