Emerging cases of drug resistance against Artemisinin combination therapies which are the current and the last line of defense against malaria makes the situation very alarming. Due to the liability of single-target drugs to be more prone to drug resistance, the trend of development of dual or multi-target inhibitors is emerging. Recently, a malaria box molecule, MMV007571 which is a well known new permeability pathways inhibitor was investigated to be also multi-targeting Plasmodium falciparum dihydroorotate dehydrogenase and cytochrome bc1 complex.
Artemisinin-based combination therapies (ACTs) have been able to reduce the clinical and pathological malaria cases in endemic areas around the globe. However, recent reports have shown a progressive decline in malaria parasite clearance in South-east Asia after ACT treatment, thus envisaging a need for new artemisinin (ART) derivatives and combinations. To address the emergence of drug resistance to current antimalarials, here we report the synthesis of artemisinin-peptidyl vinyl phosphonate hybrid molecules that show superior efficacy than artemisinin alone against chloroquine-resistant as well as multidrug-resistant Plasmodium falciparum strains with EC50 in pico-molar ranges.
Drug-resistant falciparum malaria is an increasing public health burden. This study examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam.
Mutations in the Plasmodium falciparum genes Pfdhfr and Pfdhps, particularly the sextuple mutant haplotype threatens the antimalarial effectiveness of sulfadoxine-pyrimethamine as intermittent preventive treatment during pregnancy (IPTp). To explore the impact of sextuple mutant haplotype infections on outcome measures after provision of IPTp-SP, we monitored birth outcomes in women followed from prior to conception or from the first trimester until delivery.
4-chloro eugenol (4CE), a semisynthetic analog of phytomolecule eugenol exhibited potent antiplasmodial activity with IC50 in the range of 1.5–5 μM against sensitive as well as drug resistant strain of P. falciparum. This analog also showed synergy with a clinically used antimalarial drug artesunate and was able to curtail the IC50 of artesunate up to 4–5 folds. Although, 4CE did not show any effect on heme polymerization, the most common drug target in the malaria parasite, it could increase the level of reactive oxygen species (ROS) and reactive nitrogen species (RNS) alone as well as in combination with artesunate.
Plasmodium vivax causes significant public health problems in endemic regions. A vaccine to prevent disease is critical, considering the rapid spread of drug-resistant parasite strains, and the development of hypnozoites in the liver with potential for relapse. A minimally effective vaccine should prevent disease and transmission while an ideal vaccine provides sterile immunity. Areas covered: Despite decades of research, the complex life cycle, technical challenges and a lack of funding have hampered progress of P. vivax vaccine development.
Nigeria bears 25% of global malaria burden despite concerted efforts towards its control and elimination. The emergence of drug resistance to first line drugs, artemisinin combination therapies (ACTs), indicates an urgent need for continuous molecular surveillance of drug resistance especially in high burden countries where drug interventions are heavily relied on. This study describes mutations in Plasmodium falciparum genes associated with drug resistance in malaria; Pfk13, Pfmdr1, PfATPase6 and Pfcrt in isolates obtained from 83 symptomatic malaria patients collected in August 2014, aged 1–61 years old from South-west Nigeria.
Emerging cases of drug resistance against Artemisinin combination therapies which are the current and the last line of defense against malaria makes the situation very alarming. Due to the liability of single-target drugs to be more prone to drug resistance, the trend of development of dual or multi-target inhibitors is emerging. Recently, a malaria box molecule, MMV007571 which is a well known new permeability pathways inhibitor was investigated to be also multi-targeting Plasmodium falciparum dihydroorotate dehydrogenase and cytochrome bc1 complex. The aspiration behind this study was to use the information of its pharmacophoric features essential for binding as two of its new targets.
Successful control programs have impeded local malaria transmission in almost all Gulf Cooperation Council (GCC) countries: Qatar, Bahrain, Kuwait, Oman, the United Arab Emirates (UAE) and Saudi Arabia. Nevertheless, a prodigious influx of imported malaria via migrant workers sustains the threat of local transmission. Here we examine the origin of imported malaria in Qatar, assess genetic diversity and the prevalence of drug resistance genes in imported Plasmodium falciparum, and finally, address the potential for the reintroduction of local transmission.
The ongoing spread of artemisinin resistant Plasmodium falciparum malaria is a major threat to global health. In response, countries in the Greater Mekong Sub-region, including Cambodia, have declared ambitious goals to eliminate malaria. Major challenges include the lack of information on the at-risk population-individuals who live or work in or near the forest where the malaria vectors are found, including plantation workers. This study aimed to address this knowledge gap through a cross-sectional survey conducted in rubber plantations in Cambodia in 2014.