Article
Chemistry, Medicinal
Hao Zhang, John Ginn, Wenhu Zhan, Annie Leung, Yi J. Liu, Akinori Toita, Rei Okamoto, Tzu-Tshin Wong, Toshihiro Imaeda, Ryoma Hara, Mayako Michino, Takafumi Yukawa, Sevil Chelebieva, Patrick K. Tumwebaze, Jeremie Vendome, Thijs Beuming, Kenjiro Sato, Kazuyoshi Aso, Philip J. Rosenthal, Roland A. Cooper, Nigel Liverton, Michael Foley, Peter T. Meinke, Carl F. Nathan, Laura A. Kirkman, Gang Lin
Summary: Targeting the Plasmodium proteasome is a promising strategy to combat malaria, especially with the increasing reports of resistance to current therapies. In this study, we conducted structure-activity relationship studies on a macrocyclic scaffold and identified compound TDI-8414, which showed potent antiparasitic activity, high selectivity, improved solubility, and enhanced metabolic stability.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Elizabeth A. Lopes, Maria M. M. Santos, Mattia Mori
Summary: This article summarizes the recent patents on antimalarial small molecules and vaccines, highlighting the progress made in designing new drugs and their efficacy in animal models.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Article
Immunology
Fang Huang, Christopher G. Jacob, Shannon Takala-Harrison, Matthew Adams, Heng-Lin Yang, Hui Liu, Zhi-Gui Xia, Shui-Sen Zhou, Lin-Hua Tang, Christopher V. Plowe
Summary: The study identified artemisinin resistance in parasites from Southern China and demonstrated the utility of SNP microarrays for large-scale parasite molecular epidemiology. The prevalence of resistance haplotypes and specific genetic loci associated with delayed parasite clearance were analyzed, revealing a substructure within parasite populations in Yunnan province and Hainan island.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Jerome Dormoi, Remy Amalvict, Mathieu Gendrot, Bruno Pradines
Summary: The untreated malaria can quickly progress to severe forms, and drug resistance poses a threat to malaria protection efforts worldwide. Therefore, the development of new chemotherapy is necessary. This study contributes new data on the use of methylene blue (MB) in combination with common antimalarial drugs for the treatment of malaria and cerebral malaria. The results show that the combination of MB and AQ is a good candidate for preventing cerebral malaria.
Article
Microbiology
Ryan Arey, Brad Reisfeld
Summary: A whole-body PBPK model was developed to predict the pharmacokinetic characteristics of artemisinin and its metabolite in blood, plasma, and tissues, showing good agreement with validation data. This tool is expected to improve dosing regimens by enabling a quantitative assessment of tissue-specific drug levels.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Chemistry, Medicinal
Monika Shukla, Komal Rathi, Mohammad Hassam, Dinesh Kumar Yadav, Manvika Karnatak, Varun Rawat, Ved Prakash Verma
Summary: The demand for novel, fast-acting, and effective antimalarial medications is rapidly increasing due to the spread of multidrug resistant forms of malaria parasites. Various strategies have been employed to address drug resistance, including targeted therapies, the hybrid drug idea, and the development of advanced analogues of existing drugs. The 1,2,4-trioxane ring system in artemisinin (ART) has been identified as a key pharmacophoric moiety for the potential of endoperoxide-based antimalarials.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Multidisciplinary Sciences
Moses Ocan, Fred Katabazi Ashaba, Savannah Mwesigwa, Kigozi Edgar, Moses R. Kamya, Sam L. Nsobya
Summary: This study investigated the mutations associated with artemisinin resistance in Plasmodium falciparum parasites in Uganda. The results showed a significant increase in the prevalence of pfmdr-2 gene mutations in samples collected from 2005 to 2013, while the prevalence of K13 and arps10 gene mutations did not change significantly. The findings suggest the need for continuous surveillance of molecular markers of artemisinin resistance in malaria-affected regions.
Article
Immunology
Julia C. Cutts, Katherine O'Flaherty, Sophie G. Zaloumis, Elizabeth A. Ashley, Jo Anne Chan, Marie A. Onyamboko, Caterina Fanello, Arjen M. Dondorp, Nicholas P. Day, Aung Pyae Phyo, Mehul Dhorda, Mallika Imwong, Rick M. Fairhurst, Pharath Lim, Chanaki Amaratunga, Sasithon Pukrittayakamee, Tran Tinh Hien, Ye Htut, Mayfong Mayxay, M. Abdul Faiz, Eizo Takashima, Takafumi Tsuboi, James G. Beeson, Francois Nosten, Julie A. Simpson, Nicholas J. White, Freya J. Fowkes
Summary: The substantially shorter parasite clearance time observed in African patients compared to Asian patients after artemisinin treatment cannot be explained by differences in P. falciparum antibody responses.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Cell Biology
Erin S. Coonahan, Kyung-Ae Yang, Stevan Pecic, Maarten De Vos, Thomas E. Wellems, Michael P. Fay, John F. Andersen, Joel Tarning, Carole A. Long
Summary: The development of aptamer-based fluorescent sensors for rapid detection of antimalarial compounds piperaquine and mefloquine is reported. Highly selective DNA aptamers were successfully identified and adapted into structure-switching aptamer fluorescent sensors for drug detection in human serum and crushed tablets. The sensor platform offers a rapid, inexpensive method for tracking antimalarial drug use and quality, with potential for detecting other small-molecule drugs.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Hanna Y. Ehrlich, Amy K. Bei, Daniel M. Weinberger, Joshua L. Warren, Sunil Parikh
Summary: Resistance to artemisinin-based combination therapies (ACTs) poses a threat to global malaria control, with persistent circulation of parasite alleles associated with reduced partner drug susceptibility contributing to clinical resistance. Rainfall seasonality was identified as the strongest predictor of wild-type genotype prevalence, with other covariates showing weaker associations. Our models estimated a decrease in prevalence of the pfcrt 76T mutation in 90% of regions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Soy Ty Kheang, Rosemarie Ridley, Eng Ngeth, Por Ir, Pengby Ngor, Siv Sovannaroth, Dysoley Lek, Somaly Phon, Neeraj Kak, Shunmay Yeung
Summary: Cambodia aims to eliminate malaria, but tackling P.v presents multiple challenges. The design, implementation, and evaluation of a new care pathway for radical cure treatment is crucial.
Review
Biotechnology & Applied Microbiology
Jair L. Siqueira-Neto, Kathryn J. Wicht, Kelly Chibale, Jeremy N. Burrows, David A. Fidock, Elizabeth A. Winzeler
Summary: Recent efforts in antimalarial drug discovery aim to develop new drugs that can overcome emerging drug resistance, consider safety and improve dosing convenience. These efforts have led to the discovery of a variety of new molecules with novel modes of action, some of which are currently in late-stage clinical development. Prioritizing new drug candidates is crucial due to limited funding, and these candidates should demonstrate high potency, low resistance, infrequent dosing, low cost, safety and tolerability, and preferably the ability to block Plasmodium transmission. This review provides insights into successful approaches, progress in preclinical and clinical development, and challenges in antimalarial drug discovery.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Article
Microbiology
Shalini Nair, Xue Li, Grace A. Arya, Marina McDew-White, Marco Ferrari, Tim Anderson
Summary: Drug resistance mutations disrupt key physiological processes and carry fitness costs, affecting their spread in natural populations. Standardized culture medium used for measuring fitness may underestimate these costs. This study shows that fitness costs are significantly underestimated in rich culture medium and are strongly affected by the composition of the medium.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Nanoscience & Nanotechnology
Xinyi Wang, Yiwei Xie, Ning Jiang, Jingyi Wang, Hongrui Liang, Dingyuan Liu, Na Yang, Xiaoyu Sang, Ying Feng, Ran Chen, Qijun Chen
Summary: This study developed a targeted drug delivery system for malaria treatment by preparing ferrite nanoparticles with ferromagnetic properties and loading them with artemisinin and heparin. The nanoparticles effectively targeted parasite-infected erythrocytes and interfered with the release of merozoites, enhancing the inhibitory efficacy of the antimalarial drug. Furthermore, the heparin-coated nanoparticles showed stronger blocking capability against malaria compared to free heparin due to multivalent interactions with surface receptors on merozoites.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Review
Pharmacology & Pharmacy
Yuanyuan Zou, Nadia Julie, Shiyuan Guo, Yexiao Tang, Hongying Zhang, Zhiyong Xu, Wanting Wu, Yueming Yuan, Zhibin Wu, Wenfeng Guo, Changqing Li, Xinan Huang, Qin Xu, Changsheng Deng, Jianping Song, Qi Wang
Summary: This meta-analysis aimed to analyze the effects of artemisinin and its derivatives as well as non-artemisinin drugs on gametocytes during the treatment of falciparum malaria. The results showed that artemisinin-based combination therapy had a significant effect in preventing gametocythemia, but did not control the recrudescence rate and overall cure.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Phornpimon Tipthara, Kevin C. Kobylinski, Markus Godejohann, Borimas Hanboonkunupakarn, Alison Roth, John H. Adams, Nicholas J. White, Podjanee Jittamala, Nicholas P. J. Day, Joel Tarning
Summary: Ivermectin metabolites primarily involve demethylation and hydroxylation, with M1, M3, and M6 being the main metabolites produced by CYP3A4. Further studies are needed to characterize the pharmacokinetic properties and mosquito-lethal activity of these metabolites.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2021)
Review
Pharmacology & Pharmacy
Nicholas J. White, James A. Watson, J. Kevin Baird
Summary: Methaemoglobin is the result of iron oxidation from ferrous to ferric in the haem moiety of haemoglobin. The dose-dependent methaemoglobinaemia caused by 8-aminoquinoline antimalarial drugs appears to have some connection, although not a direct one, to the therapeutic efficacy against latent Plasmodium vivax and Plasmodium ovale malarias (radical cure). Iatrogenic methaemoglobinaemia can be a useful measure in optimizing the drug and dose of 8-aminoquinoline drugs.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Editorial Material
Parasitology
James A. Watson, Nicholas J. White, Arjen M. Dondorp
Summary: Balancing selection maintains equilibrium allele frequencies of hemoglobin S between 15% and 20% in areas of high Plasmodium falciparum transmission, driven by the malaria-protective effect of sickle-cell trait. Based on this, malaria-attributable childhood mortality in the pretreatment era is estimated to be between 15% and 24%.
TRENDS IN PARASITOLOGY
(2022)
Editorial Material
Hematology
Nicholas J. White
Summary: This study investigated the predictors of malaria-associated anemia in Malian children. Anemia is a common manifestation of severe malaria, especially in young children. It is prevalent during the rainy season, and severe malarial anemia often requires blood transfusion. Additionally, severe malarial anemia is associated with high mortality and long-term neurocognitive impairment in children.
Article
Pharmacology & Pharmacy
Palang Chotsiri, Joel Tarning, Richard M. Hoglund, James A. Watson, Nicholas J. White
Summary: This study characterizes the pharmacokinetics and electrocardiographic effects of chloroquine and azithromycin, and finds that chloroquine prolongs the cardiac intervals while azithromycin has minimal additional effect. There is no drug-drug interaction between chloroquine and azithromycin.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Parasitology
Nicholas J. White
TRENDS IN PARASITOLOGY
(2022)
Review
Parasitology
Palang Chotsiri, Nicholas J. White, Joel Tarning
TRENDS IN PARASITOLOGY
(2022)
Editorial Material
Public, Environmental & Occupational Health
James A. Watson, Marian Warsame, Thomas J. Peto, Marie Onyamboko, Caterina Fanello, Arjen M. Dondorp, Nicholas White
Editorial Material
Medicine, General & Internal
Lindsey Baden, Flaminia Catteruccia, Abdoulaye Diabate, Cristina Donini, Francois Nosten, Scott O'Neill, Faith Osier, Aung Pyae Phyo, Nicholas White
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Public, Environmental & Occupational Health
Thomas J. Peto, James A. Watson, Nicholas J. White, Arjen M. Dondorp
Summary: The recent World Health Organization moratorium on rectal artesunate (RAS) for pre-referral treatment of severe childhood malaria is leading to unnecessary deaths. The decision was based on flawed findings from an observational study that provided RAS to undertrained and unsupervised community health workers. However, there is strong evidence that RAS is effective in saving lives and the delay in its deployment is causing preventable deaths.
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE
(2023)
Article
Pharmacology & Pharmacy
Ali Haghiri, David J. Price, Phoebe Fitzpatrick, Saber Dini, Megha Rajasekhar, Caterina Fanello, Joel Tarning, James Watson, Nicholas J. White, Julie A. Simpson
Summary: The majority of deaths from malaria occur in young African children, so it is important to determine the appropriate dosage of medication for them. The US FDA has challenged the World Health Organization's recommendation of a lower dose for younger children, but a study showed that younger children given the lower dose did not reach the same drug exposures as older children. Therefore, it is suggested to withdraw the FDA's recent lower dose recommendation.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Infectious Diseases
Sompob Saralamba, Julie A. Simpson, Noppon Choosri, Lisa White, Wirichada Pan-Ngum, Arjen M. Dondorp, Nicholas J. White
Summary: A new pharmacodynamic model of antimalarial drugs is proposed, which includes reversible parasite injury and temporary drug refractoriness, to explain the failure of frequent dosing to improve therapeutic efficacy in malaria. The model predicts and supports observed therapeutic responses.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Medicine, General & Internal
James A. Watson, Thomas J. Peto, Nicholas J. White
Article
Medicine, General & Internal
Aye Sandar Zaw, Ei Shwe Sin Win, Soe Wai Yan, Kyaw Sithu Thein, Vasundhara Verma, Alistair R. D. Mclean, Thar Tun Kyaw, Nicholas J. White, Frank M. Smithuis
Summary: The introduction of community health workers providing early diagnosis and treatment for malaria in remote communities in Mon state, Myanmar, has resulted in a significant reduction in malaria cases.