Malaria Therapy Research Articles

Assessment of Malaria Pharmacotherapeutic Outcomes in Children under 12 Years of Age among Three Health-care Facilities, Bayelsa, Nigeria

Abstract Background: Malaria is Nigeria’s biggest public health problem, accounting for around 30% of all fatalities among children under 5 years, 25% of infant deaths, and 11% of maternal mortality. Aims and Objectives: The study aimed to identify the outcomes of malaria therapy in children under 12 who were admitted and managed at three health facilities in Bayelsa State, Nigeria, and if the treatment pattern adhered to standard guidelines. Materials and Methods: A detailed retrospective survey was designed, and a data collection instrument was utilized to obtain clinical, medical, and medication histories for children from the selected health facilities between January 2019 and June 2020. The survey collected data from 1312 children. The data were analyzed using a Chi-square test in SPSS version 23.0 and Microsoft Excel 2013. Results: From the data obtained, only 37.73% of the 1312 participants underwent a malaria parasite (MP) test. The most common diagnosis made at the Primary HealthCare Center (PHC) was acute/uncomplicated malaria (43.0%), followed by diarrhea (21.3%), and gastroenteritis (GET) with upper respiratory tract infection (15.7%). The most common diagnoses for Secondary HealthCare Center (SEC) and Federal/Tertiary HealthCare Center (FHI) were malaria with GET (22.5%) and severe malaria with meningitis (18.1%). The majority of patients were effectively handled and discharged, FHI (73.0%), SEC (91.1%), and PHC (94.0%). Other notable outcomes included patients’ task capacity and a temperature decreased to normal (TDN). Conclusion: There was a significant correlation between demographic data and treatment outcomes (P < 0.05). Although the three health facilities provided competent patient management along with appropriate prescription trends for malaria and comorbidities, there was a low proportion of patients who received an MP test, particularly at the FHI.

Grasp of dihydroartemisinin resistance in Indonesia: Focused on genetic polymorphisms and new antimalarial.

The eastern region of Indonesia is endemic to malaria, a tropical parasitic infection that causes significant mortality. The Sustainable Development Goals (SDGs) encompass the global commitment to prevent and eliminate malaria by the end of 2030. Nevertheless, the biggest issue lies in the antimalarial drug resistance in Indonesia. Genetic polymorphism has been a considerable factor in the mechanism of antimalarial drug resistance of which could lead to inadequate activity of antimalarial drugs to undertake Plasmodium infection by several molecular mechanisms. Hence, first-line therapy for malaria in Indonesia such as dihydroartemisinin, piperaquine, and primaquine, becomes ineffective. However, the resistance is unavoidable. This review aims to summarize the genetic polymorphism possible mechanisms contributing to antimalarial resistance in the Indonesian population and to discuss the potential new antimalarial drug candidates.

The RNA-binding KH-domain in the unique transcription factor of the malaria parasite is responsible for its transcriptional regulatory activity.

To date, only a small number of regulatory transcription factors have been predicted from the genome of Plasmodium and Apicomplexan parasites. We previously identified a nuclear factor named Prx regulatory element-binding protein (PREBP) from Plasmodium falciparum. PREBP had been suggested to bind to the cis-element in the promoter of an antioxidant pf1-cys-prx gene, thereby promoting the expression of downstream genes. PREBP has 4 putative K homology (KH) domains, which are known to bind RNA and single-stranded DNA. In this study, to understand the detailed action of PREBP in parasite cells, we first observed that in living parasite cells, PREBP was localized in the nucleus in the trophozoite and schizont stages, in which the expression of the target pf1-cys-prx was enhanced. The interaction of PREBP and the cis-element of pf1-cys-prx in the parasite cells was also confirmed. Further, the activities of PREBP deletion mutants were analyzed, and regions with repeated KH domains in PREBP seemed to be responsible for the recognition of the cis-element. These results led us to hypothesize that Plasmodium and other Apicomplexan parasites might have a transcription factor family with KH domains. Bioinformatic analysis revealed a putative ortholog group including PREBP and several Plasmodium and Apicomplexan factors with KH domains. One of the P. falciparum-derived factors, which were included in the putative ortholog group, was found to be localized at the nucleus in the trophozoite stage, indicating that it might be a novel transcription factor. The discovery of PREBP and putative transcription factors with KH domains suggested that multi-functional proteins with KH domains possibly evolved in the Apicomplexan organisms. They might play key roles in transcriptional regulatory processes that are essential for living organisms and may even represent unique drug targets for malaria therapy.

An Ill-bred Culture of Experimentation: Malaria Therapy and Race in the United States Public Health Service Laboratory at the South Carolina State Hospital, 1932-1952

Abstract While most are aware of the Tuskegee syphilis experiments in which African American syphilis patients went untreated, less is known about experiments with malaria fever therapy conducted upon syphilis patients during the same period by the Unites States Public Health Service at the Williams Laboratory on the grounds of the South Carolina State Hospital (SCSH) in Columbia, SC. Over a twenty-year period, physicians maintained patients as malaria reservoirs for patient-to-patient inoculation and subjected patients to extreme fevers and thousands upon thousands of insect bites as part of a program in which one disease was tested as therapy for another. Using extant administrative files, medical journals from the period, and a database created from SCSH annual reports, this paper considers the ethics of malaria fever therapy experiments while exposing the conditions under which patients suffered the intersecting oppressions of race, class, and mental illness. It illuminates the prevalent scientific racism of the period that enabled pseudo-medical assumptions about African Americans’ perceived penchant for poverty, deviant sex, and pain tolerance, which combined to enable a culture of experimentation that influenced events at Stateville Penitentiary and continued long after penicillin became widely available.

Anti-malarial and haematological evaluation of the ethanolic, ethyl acetate and aqueous fractions of Chromolaena odorata

Malaria is a global health challenge with endemicity in sub-Saharan Africa, where there are multiple drug-resistant strains and limited access to modern health care facilities, especially in rural areas. Studies indicate that African traditional medicine could make a substantial contribution to the reduction of malaria-related deaths and achievement of universal health coverage (UHC), particularly in these regions. Thus, this study evaluated the curative antimalarial effects of Chromolaena odorata leaf extract using mouse model. Forty-five (45) albino mice weighing between 18 and 22 g were grouped into nine groups of 5 animals each. Animals in groups 2–9 were infected with the chloroquine-resistant strain of Plasmodium berghei, while animals in groups 3–9 were subsequently treated with 10 mg/kg chloroquine, a combination of 1.4 mg/kg artemether and 8.75 mg/kg lumefantrine (Coartem), and varying concentrations of the fraction from the aqueous leaf extract of C. odorata at day 3 post-infection. The findings from this study indicate that treatment with 400 mg/kg of the ethanolic fraction of the crude extract resulted in a significant decrease in parasite load (97.6%), which was comparable to the activities of the conventional drugs chloroquine (98.6%) and Coartem (98.8%). The ethyl acetate and ethanolic fractions at 400 mg/kg also ameliorated the significant alterations in the red blood cells, white blood cells, and platelets of the infected animals. The high antimalarial activity displayed by the ethanolic fraction could be due to the presence of quercetin and kaempferol, as detected by high performance liquid chromatography (HPLC) analysis. The findings suggest that the fractions from C. odorata could serve as an alternative source of malaria therapy, particularly in sub-Saharan Africa.

Artesunate-mefloquine therapy for uncomplicated Plasmodium falciparum malaria: an updated systematic review and meta-analysis of efficacy and safety.

To provide a continuous update on the safety and efficacy of artesunate-mefloquine (ASMQ) compared with other artemisinin combination therapy (ACT) schemes used in the treatment of uncomplicated malaria caused by Plasmodium falciparum, this study updated and expanded the results of the systematic literature review published in 2016. Only randomised controlled clinical trials published from 1 January 2001 to 12 June 2023 from five databases were included in this study. The results related to efficacy, expressed through RR, were summarized in meta-analyses, performed according to the compared ACTs and with the intention-to-treat and per-protocol analyses. The results related to safety were synthesized in a descriptive manner. Thirty-two studies were included, of which 24 had been analysed in the 2016 review and eight new ones were added. Although the methodological quality of most studies was considered moderate, the body of evidence gathered indicates that ASMQ continues to be safe and effective for the treatment of uncomplicated infections caused by P. falciparum compared with other ACTs. However, the inclusion of two new studies, which identified failure rates exceeding 10%, suggests a possible reduction in the efficacy of ASMQ in the analysed locations. The incidence of serious adverse effects, such as seizure, encephalopathy and cardiac arrhythmia, was infrequent in both the ASMQ group and the comparison groups. After including new evidence, ASMQ is still recommended as a first-line treatment of uncomplicated malaria caused by P. falciparum, although local aspects need to be considered.

Increasing Prevalence of Artemisinin-Resistant HRP2-Negative Malaria in Eritrea

BackgroundAlthough the clinical efficacy of antimalarial artemisinin-based combination therapies in Africa remains high, the recent emergence of partial resistance to artemisinin in Plasmodium falciparum on the continent is troubling, given the lack of alternative treatments.MethodsIn this study, we used data from drug-efficacy studies conducted between 2016 and 2019 that evaluated 3-day courses of artemisinin-based combination therapy (artesunate–amodiaquine or artemether–lumefantrine) for uncomplicated malaria in Eritrea to estimate the percentage of patients with day-3 positivity (i.e., persistent P. falciparum parasitemia 3 days after the initiation of therapy). We also assayed parasites for mutations in Pfkelch13 as predictive markers of partial resistance to artemisinin and screened for deletions in hrp2 and hrp3 that result in variable performance of histidine rich protein 2 (HRP2)–based rapid diagnostic tests for malaria.ResultsWe noted an increase in the percentage of patients with day-3 positivity from 0.4% (1 of 273) in 2016 to 1.9% (4 of 209) in 2017 and 4.2% (15 of 359) in 2019. An increase was also noted in the prevalence of the Pfkelch13 R622I mutation, which was detected in 109 of 818 isolates before treatment, from 8.6% (24 of 278) in 2016 to 21.0% (69 of 329) in 2019. The odds of day-3 positivity increased by a factor of 6.2 (95% confidence interval, 2.5 to 15.5) among the patients with Pfkelch13 622I variant parasites. Partial resistance to artemisinin, as defined by the World Health Organization, was observed in Eritrea. More than 5% of the patients younger than 15 years of age with day-3 positivity also had parasites that carried Pfkelch13 R622I. In vitro, the R622I mutation conferred a low level of resistance to artemisinin when edited into NF54 and Dd2 parasite lines. Deletions in both hrp2 and hrp3 were identified in 16.9% of the parasites that carried the Pfkelch13 R622I mutation, which made them potentially undetectable by HRP2-based rapid diagnostic tests.ConclusionsThe emergence and spread of P. falciparum lineages with both Pfkelch13-mediated partial resistance to artemisinin and deletions in hrp2 and hrp3 in Eritrea threaten to compromise regional malaria control and elimination campaigns. (Funded by the Bill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry numbers, ACTRN12618001223224, ACTRN12618000353291, and ACTRN12619000859189.)

Curcumin‐loaded nanomedicines as therapeutic strategy in malaria management

AbstractMalaria, a parasitic protozoan disease widespread in tropical climates, is transmitted by Plasmodium spp. Many people are affected by this significant public health disease, which has a high incidence of illness and mortality worldwide. Because drug‐resistant parasites are on the rise, there are not enough controls on mosquitoes, and there are not any malaria vaccinations. Malaria is particularly challenging in developing countries. Antimalarial drugs approved by Food and Drug Administration are the main options for combating and preventing malaria; also the control of transmission at the level of mosquitoes is important. Current antimalarial chemotherapeutic therapies have significant clinical flaws such as Plasmodium resistance, the drugs that call for the development of novel drug candidates. To combat malaria, nanotechnology may give a viable alternative that is both more effective and safer than current treatment options. Nanotechnology‐based curcumin formulations have proved to overcome the limitations of current therapies in terms of optimum therapeutic benefits, safety, and cost‐efficiency, which increases a patient's capacity to adhere to prescribed medicine. The limits of current malaria therapies and the need to employ nanotechnological curcumin to treat malaria were addressed and discussed in this paper.

Indigenous medicinal plants used in folk medicine for malaria treatment in Kwara State, Nigeria: an ethnobotanical study

BackgroundFolk medicine is crucial to healthcare delivery in the underdeveloped countries. It is frequently used as a primary treatment option or as a complementary therapy for malaria. Malaria is a deadly disease which greatly threatens global public health, claiming incredible number of lives yearly. The study was aimed at documenting the medicinal plants used for malaria treatment in folk medicine in Kwara State, Nigeria.MethodsEthnobotanical information was collected from selected consenting registered traditional medicine practitioners (TMPs) through oral face-to-face interviews using in-depth, semi-structured interview guide. The ethnobotanical data were analysed, and descriptive statistical methods were used to compile them.ResultsSixty-two indigenous medicinal plants, including 13 new plants, used for malaria treatment were identified in this study. The TMPs preferred decoction in aqueous solvent (34%) and steeping in decaffeinated soft drink (19%) for herbal preparations. Oral administration (74%) was the main route of administration, while leaves (40%) and stem barks (32%) were the most dominant plant parts used in herbal preparations. The most cited families were Fabaceae (15%) and Rutaceae (6%), while Mangifera indica (77.14%), Enantia chlorantha (65.71%), Alstonia boonei (57.14%) followed by Cymbopogon citratus (54.29%) were the most used plants. Besides, the antimalarial activities of many of the plants recorded and their isolated phytocompounds have been demonstrated. Furthermore, the conservation status of 4 identified plants were Vulnerable.ConclusionThe study showed strong ethnobotanical knowledge shared by the TMPs in the State and provides preliminary information that could be explored for the discovery of more potent antimalarial compounds.

Comparative investigation on interaction between potent antimalarials and human serum albumin using multispectroscopic and computational approaches.

This study performed a comparative investigation to explore the interaction mechanisms between two potential antimalarial compounds, JMI 346 and JMI 105, and human serum albumin (HSA), a vital carrier protein responsible for maintaining important biological functions. Our aim was to assess the pharmacological efficiency of these compounds while comprehensively analyzing their impact on the dynamic behavior and overall stability of the protein. A comprehensive array of multispectroscopic techniques, including UV-Vis. spectroscopy, steady-state fluorescence analysis, synchronous fluorescence spectroscopy, three-dimensional fluorescence and circular dichroism spectroscopy, docking studies, and molecular dynamics simulations, were performed to probe the intricate details of the interaction between the compounds and HSA. Our results revealed that both JMI 346 and JMI 105 exhibited promising pharmacological effectiveness within the context of malaria therapy. However, JMI 346 was found to exhibit a significantly higher affinity and only minor altered impact on HSA, suggesting a more favorable interaction with the protein on the dynamic behavior and overall stability of the protein in comparison to JMI 105. Further studies can build on these results to optimize the drug-protein interaction and enable the development of more potent and targeted antimalarial treatments.

Xanthine oxidase levels and immune dysregulation are independently associated with anemia in Plasmodium falciparum malaria

Severe anemia is an important contributor to mortality in children with severe malaria. Anemia in malaria is a multi-factorial complication, since dyserythropoiesis, hemolysis and phagocytic clearance of uninfected red blood cells (RBCs) can contribute to this syndrome. High levels of oxidative stress and immune dysregulation have been proposed to contribute to severe malarial anemia, facilitating the clearance of uninfected RBCs. In a cohort of 552 Ugandan children with severe malaria, we measured the levels of xanthine oxidase (XO), an oxidative enzyme that is elevated in the plasma of malaria patients. The levels of XO in children with severe anemia were significantly higher compared to children with severe malaria not suffering from severe anemia. Levels of XO were inversely associated with RBC hemoglobin (ρ = − 0.25, p < 0.0001), indicating a relation between this enzyme and severe anemia. When compared with the levels of immune complexes and of autoimmune antibodies to phosphatidylserine, factors previously associated with severe anemia in malaria patients, we observed that XO is not associated with them, suggesting that XO is associated with severe anemia through an independent mechanism. XO was associated with prostration, acidosis, jaundice, respiratory distress, and kidney injury, which may reflect a broader relation of this enzyme with severe malaria pathology. Since inhibitors of XO are inexpensive and well-tolerated drugs already approved for use in humans, the validation of XO as a contributor to severe malarial anemia and other malaria complications may open new possibilities for much needed adjunctive therapy in malaria.

Evaluation of 4-Aminoquinoline Hydrazone Analogues as Potential Leads for Drug-Resistant Malaria.

The emergence of resistance to first-line antimalarial drugs calls for the development of new therapies for drug-resistant malaria. The efficacy of quinoline-based antimalarial drugs has prompted the development of novel quinolines. A panel of 4-aminoquinoline hydrazone analogues were tested on the multidrug-resistant K1 strain of Plasmodium falciparum: IC50 values after a 48 h cycle ranged from 0.60 to 49 µM, while the 72 h cycle ranged from 0.026 to 0.219 μM. Time-course assays were carried out to define the activity of the lead compounds, which inhibited over 50% growth in 24 h and 90% growth in 72 h. Cytotoxicity assays with HepG2 cells showed IC50 values of 0.87-11.1 μM, whereas in MDBK cells, IC50 values ranged from 1.66 to 11.7 μM. High selectivity indices were observed for the lead compounds screened at 72 h on P. falciparum. Analyses of stage specificity revealed that the ring stages of the parasite life cycle were most affected. Based on antimalarial efficacy and in vitro safety profiles, lead compound 4-(2-benzylidenehydrazinyl)-6-methoxy-2-methylquinoline 2 was progressed to drug combination studies for the detection of synergism, with a combinatory index of 0.599 at IC90 for the combination with artemether, indicating a synergistic antimalarial activity. Compound 2 was screened on different strains of P. falciparum (3D7, Dd2), which maintained similar activity to K1, suggesting no cross-resistance between multidrug resistance and sensitive parasite strains. In vivo analysis with 2 showed the suppression of parasitaemia with P. yoelii NL (non-lethal)-treated mice (20 mg/kg and 5 mg/kg).

A successful falciparum malaria treatment with hemodiafiltration in an African patient

Malaria is a serious infectious illness that has existed since ancient times. Despite its prevalence in Sub-Saharan Africa, it remains a global public health issue. However, Plasmodium falciparum causes the most severe and fatal form of malaria, accounting for almost 80% of global mortality. Malarial acute kidney injury (AKI) caused by malaria can progress rapidly. An early initiation to renal replacement therapy is advised because AKI induced by malaria may worsen fast. This paper report a successful severe malaria therapy with hemodiafiltration in the ICU of an African student studying in Turkey. The patient, whose blurring of consciousness increased and Glasgow coma scale (GCS) decreased GCS=8, was admitted to the anesthesiology and reanimation ICU. The patient was treated for 3 days with malaria medications and continuous renal replacement therapy (CRRT). Malaria persists everywhere, especially among nonimmunized people. AKI is common in malaria patients. Patients with severe malaria should be examined for renal involvement, including electrolyte abnormalities and fluid overload. Supportive treatment is recommended for oliguric AKI. If feasible, CRRT may help these patients.

Pyronaridine: a review of its clinical pharmacology in the treatment of malaria.

Pyronaridine-artesunate was recently strongly recommended in the 2022 update of the WHO Guidelines for the Treatment of Malaria, becoming the newest artemisinin-based combination therapy (ACT) for both uncomplicated Plasmodium falciparum and Plasmodium vivax malaria. Pyronaridine-artesunate, available as a tablet and paediatric granule formulations, is being adopted in regions where malaria treatment outcome is challenged by increasing chloroquine resistance. Pyronaridine is an old antimalarial agent that has been used for more than 50 years as a blood schizonticide, which exerts its antimalarial activity by interfering with the synthesis of the haemozoin pigment within the Plasmodium digestive vacuole. Pyronaridine exhibits a high blood-to-plasma distribution ratio due to its tendency to accumulate in blood cells. This feature is believed to play a crucial role in its pharmacokinetic (PK) properties and pharmacological activity. The PK characteristics of pyronaridine include rapid oral absorption, large volumes of distribution and low total body clearance, resulting in a long terminal apparent half-life. Moreover, differences in PK profiles have been observed between healthy volunteers and malaria-infected patients, indicating a potential disease-related impact on PK properties. Despite a long history, there is only limited knowledge of the clinical PK and pharmacodynamics of pyronaridine, particularly in special populations such as children and pregnant women. We here provide a comprehensive overview of the clinical pharmacology of pyronaridine in the treatment of malaria.

Reversing artemisinin resistance by leveraging thermo-responsive nanoplatform to downregulating GSH

Artemisinin (ART) resistance has been an emerging clinical problem, severely compromising antimalarial efficacy and threatening the global malaria elimination campaign. Albeit intensive studies about the molecular mechanism for ART resistance are under way, no effective therapeutic targets for reversing resistance have been applied. Here, we explore glutathione (GSH) as a therapeutic target to develop a thermo-responsive nanoplatform to specifically co-deliver ART and GSH synthesis inhibitor (l-buthionine sulfoximine, BSO) in a sustained manner, effectively reversing ART resistance in vivo. By combining with BSO, ART exerts increased antimalarial activity with reduced half-maximal inhibitory concentration (IC50) by 7.43-fold in ART-resistant strains. This work reveals that the GSH in ART-resistant parasites can be a promising therapeutic target for reversing ART resistance, paving the way for developing drug candidates and intelligent nanomedicines in malaria therapy.

Artesunate Therapy for Severe Malaria: Mechanisms, Efficacy, and Cost - Effectiveness

Artesunate Therapy for Severe Malaria: Mechanisms, Efficacy, and Cost - Effectiveness

Tautomeric equilibrium and spectroscopic properties of 8-azaguanine revealed by quantum chemistry methods.

8-azaguanine is a triazolopyrimidine nucleobase analog possessing potent antibacterial and antitumor activities, and it has been implicated as a lead molecule in cancer and malaria therapy. Its intrinsic fluorescence properties can be utilized for monitoring its interactions with biological polymers like proteins or nucleic acids. In order to better understand these interactions, it is important to know the tautomeric equilibrium of this compound. In this work, the tautomeric equilibrium of all natural neutral and anionic compound forms (except highly improbable imino-enol tautomers) as well as their methyl derivatives and ribosides was revealed by quantum chemistry methods. It was shown that, as expected, tautomers protonated at positions 1 and 9 dominate neutral forms both in gas phase and in aqueous solution. 8-azaguanines methylated at any position of the triazole ring are protonated at position 1. The computed vertical absorption and emission energies are in very good agreement with the experimental data. They confirm the validity of the assumption that replacing the proton with the methyl group does not significantly change the positions of absorption and fluorescence peaks.

Plasmodium falciparum drug resistance-associated mutations in isolates from children living in endemic areas of Burkina Faso

BackgroundArtemisinin-based combinations therapy (ACT) is the current frontline curative therapy for uncomplicated malaria in Burkina Faso. Sulfadoxine-pyrimethamine (SP) is used for the preventive treatment of pregnant women (IPTp), while SP plus amodiaquine (SP-AQ) is recommended for children under five in seasonal malaria chemoprevention (SMC). This study aimed to assess the proportions of mutations in the P. falciparum multidrug-resistance 1 (Pfmdr1), P. falciparum chloroquine resistance transporter (Pfcrt), P. falciparum dihydrofolate reductase (pfdhfr), and P. falciparum dihydropteroate synthase (pfdhps), genes from isolates collected during household surveys in Burkina Faso.MethodsDried blood spots from Plasmodium falciparum-positive cases at three sites (Orodara, Gaoua, and Banfora) collected during the peak of transmission were analysed for mutations in Pfcrt (codons 72–76, 93, 97, 145, 218, 343, 350 and 353), Pfmdr-1 (codons 86, 184, 1034, 1042 and 1246) dhfr (codons 51, 59, 108, 164) and dhps (at codons 431, 436, 437, 540, 581, 613) genes using deep sequencing of multiplexed Polymerase chaine reaction (PCR) amplicons.ResultsOf the 377 samples analysed, 346 (91.7%), 369 (97.9%), 368 (97.6%), and 374 (99.2%) were successfully sequenced for Pfcrt, Pfmdr-1, dhfr, and dhps, respectively. Most of the samples had a Pfcrt wild-type allele (89.3%). The 76T mutation was below 10%. The most frequent Pfmdr-1 mutation was detected at codon 184 (Y > F, 30.9%). The single mutant genotype (NFSND) predominated (66.7%), followed by the wild-type genotype (NYSND, 30.4%). The highest dhfr mutations were observed at codon 59R (69.8%), followed by codons 51I (66.6%) and 108 N (14.7%). The double mutant genotype (ACIRSI) predominated (52.4%). For mutation in the dhps gene, the highest frequency was observed at codon 437 K (89.3%), followed by codons 436 A (61.2%), and 613 S (14.4%). The double mutant genotype (IAKKAA) and the single mutant genotype (ISKKAA) were predominant (37.7% and 37.2%, respectively). The most frequent dhfr/dhps haplotypes were the triple mutant ACIRSI/IAKKAA (23%), the wild-type ACNCSI/ISKKAA (19%) and the double mutant ACIRSI/ISKKAA (14%). A septuple mutant ACIRNI/VAKKGA was observed in 2 isolates from Gaoua (0.5%).ConclusionThe efficacy of ACT partner drugs and drugs used in IPTp and SMC does not appear to be affected by the low proportion of highly resistant mutants observed in this study. Continued monitoring, including molecular surveillance, is critical for decision-making on effective treatment policy in Burkina Faso.

Dihydroartemisinin Disrupts Zinc Homeostasis in Plasmodium falciparum To Potentiate Its Antimalarial Action via Pyknosis.

Artemisinins have been used as first-line drugs worldwide to treat malaria caused by Plasmodium falciparum; however, its underlying mechanism is still unclear. This study aimed to identify the factors inducing growth inhibition via pyknosis, a state of intraerythrocytic developmental arrest, when exposing the parasite to dihydroartemisinin (DHA). Changes in the expression of genome-wide transcripts were assessed in the parasites treated with antimalarials, revealing the specific downregulation of zinc-associated proteins by DHA. The quantification of zinc levels in DHA-treated parasite indicated abnormal zinc depletion. Notably, the zinc-depleted condition in the parasite produced by a zinc chelator induced the generation of a pyknotic form and the suppression of its proliferation. The evaluation of the antimalarial activity of DHA or a glutathione-synthesis inhibitor in the zinc-depleted state showed that the disruption of zinc and glutathione homeostasis synergistically potentiated the growth inhibition of P. falciparum through pyknosis. These findings could help further understand the antimalarial actions of artemisinins for advancing malaria therapy.

Tafenoquine and artemisinin-based combination therapy for vivax malaria: end of the road or just the beginning?

Intense malaria control has resulted in a reduction in cases of Plasmodium falciparum malaria, but the effect is less apparent for Plasmodium vivax. Widespread access to safe and effective radical cure (the treatment of both blood and liver stages) is crucial for the elimination of P vivax and a key element for reducing morbidity associated with recurrent vivax parasitaemia. Tafenoquine co-administered with dihydroartemisinin–piperaquine for the radical cure of Plasmodium vivax malaria (INSPECTOR): a randomised, placebo-controlled, efficacy and safety studyAlthough tafenoquine plus dihydroartemisinin–piperaquine was statistically superior to dihydroartemisinin–piperaquine alone for the radical cure of P vivax malaria, the benefit was not clinically meaningful. This contrasts with previous studies in which tafenoquine plus chloroquine was clinically superior to chloroquine alone for radical cure of P vivax malaria. Full-Text PDF