Effective Antimalarial Drugs Research Articles

Treatment with specific and pan-plasma membrane calcium ATPase (PMCA) inhibitors reduces malaria parasite growth in vitro and in vivo

BackgroundRapid emergence of Plasmodium resistance to anti-malarial drug mainstays has driven a continual effort to discover novel drugs that target different biochemical pathway (s) during infection. Plasma membrane Calcium + 2 ATPase (PMCA4), a novel plasma membrane protein that regulates Calcium levels in various cells, namely red blood cell (RBC), endothelial cell and platelets, represents a new biochemical pathway that may interfere with susceptibility to malaria and/or severe malaria.MethodsThis study identified several pharmacological inhibitors of PMCA4, namely ATA and Resveratrol, and tested for their anti-malarial activities in vitro and in vivo using the Plasmodium falciparum 3D7 strain, the Plasmodium berghei ANKA strain, and Plasmodium yoelii 17XL strain as model.ResultsIn vitro propagation of P. falciparum 3D7 strain in the presence of a wide concentration range of the inhibitors revealed that the parasite growth was inhibited in a dose-dependent manner, with IC50s at 634 and 0.231 µM, respectively.ResultsThe results confirmed that both compounds exhibit moderate to potent anti-malarial activities with the strongest parasite growth inhibition shown by resveratrol at 0.231 µM. In vivo models using P. berghei ANKA for experimental cerebral malaria and P. yoelii 17XL for the effect on parasite growth, showed that the highest dose of ATA, 30 mg/kg BW, increased survival of the mice. Likewise, resveratrol inhibited the parasite growth following 4 days intraperitoneal injection at the dose of 100 mg/kg BW.ConclusionThe findings indicate that the PMCA4 of the human host may be a potential target for novel anti-malarials, either as single drug or in combination with the currently available effective anti-malarials.

Targeting Inhibition of Accumulation and Function of Myeloid-Derived Suppressor Cells by Artemisinin via PI3K/AKT, mTOR, and MAPK Pathways Enhances Anti-PD-L1 Immunotherapy in Melanoma and Liver Tumors.

Despite the remarkable success and efficacy of immune checkpoint blockade (ICB) therapy such as anti-PD-L1 antibody in treating cancers, myeloid-derived suppressor cells (MDSCs) that lead to the formation of the protumor immunosuppressive microenvironment are one of the major contributors to ICB resistance. Therefore, inhibition of MDSC accumulation and function is critical for further enhancing the therapeutic efficacy of anti-PD-L1 antibody in a majority of cancer patients. Artemisinin (ART), the most effective antimalarial drug with tumoricidal and immunoregulatory activities, is a potential option for cancer treatment. Although ART is reported to reduce MDSC levels in 4T1 breast tumor model and improve the therapeutic efficacy of anti-PD-L1 antibody in T cell lymphoma-bearing mice, how ART influences MDSC accumulation, function, and molecular pathways as well as MDSC-mediated anti-PD-L1 resistance in melanoma or liver tumors remains unknown. Here, we reported that ART blocks the accumulation and function of MDSCs by polarizing M2-like tumor-promoting phenotype towards M1-like antitumor one. This switch is regulated via PI3K/AKT, mTOR, and MAPK signaling pathways. Targeting MDSCs by ART could significantly reduce tumor growth in various mouse models. More importantly, the ART therapy remarkably enhanced the efficacy of anti-PD-L1 immunotherapy in tumor-bearing mice through promoting antitumor T cell infiltration and proliferation. These findings indicate that ART controls the functional polarization of MDSCs and targeting MDSCs by ART provides a novel therapeutic strategy to enhance anti-PD-L1 cancer immunotherapy.

Knowledge of Malaria and Its Uncomplicated Treatment with Argemone mexicana L. in Selected Districts of Jimma Zone, Oromia Regional State, Ethiopia: A Community-Based Cross Sectional Survey.

BackgroundWith the problems of increasing levels of drug resistance and difficulties to afford and access effective antimalarial drugs in poor and remote areas, herbal medicines could be an important and sustainable source of treatment. Argemone mexicana L. (AM) is a medicinal plant known long ago in several countries for treatment of numerous diseases including malaria. The aim of this study was to conduct a survey on the use of AM in the prevention and treatment of uncomplicated malaria in selected districts of Jimma Zone, Oromia Regional state, Ethiopia.MethodsA community-based cross-sectional study was conducted in two selected districts in Jimma Zone, southwest Ethiopia. In total, 552 participants from 17 kebeles (villages/communities) and 18 traditional healers of the districts were interviewed. Data collection was conducted from April 27 to May 18, 2020 using pre-tested structured questionnaires. The data were analyzed using Epi Info 7.0 and the descriptive statistics were used to summarize the results.ResultsThe study indicated that AM is available, known by 39.8% of the respondents and used for prevention and treatment of malaria by 5.7% of the population. All traditional healers interviewed knew the plant, and 44.4% use it for treatment of malaria. In addition, AM is especially used to treat malaria, amoebiasis, diarrhea, cough, and tuberculosis.ConclusionThe availability and use of AM to treat malaria was verified in both community and traditional healers. AM, which was found effective as antimalarial plant in high Plasmodium falciparum endemicity in Mali, is also well known and accepted in these areas of Ethiopia for the treatment of malaria. Further research is needed to assess wether AM is also effective against malaria in Ethiopia where P. vivax and P. falciparum coexist.

Malaria rapid diagnostic tests for the case management of febrile children in Nigerian primary healthcare settings: a cross-sectional study

BackgroundMalaria has been identified as a significant public health burden, exhibiting a high risk of death and morbidity. In sub-Saharan Africa, most young children attending primary healthcare facilities are commonly diagnosed with malaria. Thus, introduction of malaria rapid diagnostic test (mRDT) kits and effective antimalarials has substantially improved the management of malaria cases. However, healthcare worker confidence and adherence to procedures dependent on malaria test results remain variable in high-burden settings due to lacking alternative point-of-care tests to diagnose other causes of fever. In this study, we compared the results of malaria screenings using mRDT and microscopy in febrile children presenting at a primary health facility.MethodsThis study was conducted at a primary health center in Owo, Ondo State, Nigeria. Children with fever were assessed for malaria by health staff and, where indicated, screened using Plasmodium falciparum histidine-rich protein-2 mRDT kits. Blood samples were collected on slides for microscopy and in hematocrit tubes for hematocrit determination simultaneously, whereas the mRDT test was done by routine health staff. Children found positive for malaria via mRDT were diagnosed as uncomplicated malaria cases and treated as outpatients using artemether-lumefantrine. Blood slides were read independently by two trained microscopists blinded to the mRDT results. The parasite densities were defined as average counts by both microscopists. We then assessed the sensitivity, specificity, and predictive value of mRDT for the diagnosis of malaria.ResultsWe compared the test results of 250 febrile children who are under 15 years old. The test positivity rates were 93.6% (234/250) and 97.2% (243/250) using microscopy and rapid RDTs, respectively. The sensitivity and specificity of mRDT compared to microscopy were 100.0% and 43.8%, respectively, with a positive predictive value of 96.3% (95% CI 93.1–98.3). The hematocrit value was <30% in 64% of the children.ConclusionAs per our findings, mRDTs have correctly detected infections in febrile children. Healthcare workers and caregivers should be encouraged to act in accordance with the test results by means of regular feedback on the quality of mRDTs in use in malaria case management.

A Mini-Review On The Current Scenario Of Quinoline Scaffolds For Antimalarial Activity

Antimalarial agents are an important key for the prevention and eradication of malaria. The heterocyclic aromatic quinoline scaffold is a favored structure in drug development because its derivatives have a wide range of biological properties. The quinoline family contains a lot of antimalarial agents like chloroquine, piperaquine, quinine, etc. Chloroquine had been a significant antimalarial agent for more than five decades. To enhance the efficacy in malarial treatment a new system of several other quinoline-based drugs has been synthesized. This mini-review intends to provide a literature overview of antimalarial compounds containing a quinoline core, encompassing papers from 2018 to the present along with the synthesis and pertinent figures. It could be useful for researchers to design more effective antimalarial drugs in the future.

In-Silico Functional Annotation of Plasmodium falciparum Hypothetical Proteins to Identify Novel Drug Targets.

Plasmodium falciparum is one of the plasmodium species responsible for the majority of life-threatening malaria cases. The current antimalarial therapies are becoming less effective due to growing drug resistance, leading to the urgent requirement for alternative and more effective antimalarial drugs or vaccines. To facilitate the novel drug discovery or vaccine development efforts, recent advances in sequencing technologies provide valuable information about the whole genome of the parasite, yet a lot more needs to be deciphered due to its incomplete proteome annotation. Surprisingly, out of the 5,389 proteins currently annotated in the Plasmodium falciparum 3D7 strain, 1,626 proteins (∼30% data) are annotated as hypothetical proteins. In parasite genomic studies, the challenge to annotate hypothetical proteins is often ignored, which may obscure the crucial information related to the pathogenicity of the parasite. In this study, we attempt to characterize hypothetical proteins of the parasite to identify novel drug targets using a computational pipeline. The study reveals that out of the overall pool of the hypothetical proteins, 266 proteins have conserved functional signatures. Furthermore, the pathway analysis of these proteins revealed that 23 proteins have an essential role in various biochemical, signalling and metabolic pathways. Additionally, all the proteins (266) were subjected to computational structure analysis. We could successfully model 11 proteins. We validated and checked the structural stability of the models by performing molecular dynamics simulation. Interestingly, eight proteins show stable conformations, and seven proteins are specific for Plasmodium falciparum, based on homology analysis. Lastly, mapping the seven shortlisted hypothetical proteins on the Plasmodium falciparum protein-protein interaction network revealed 3,299 nodes and 2,750,692 edges. Our study revealed interesting functional details of seven hypothetical proteins of the parasite, which help learn more about the less-studied molecules and their interactions, providing valuable clues to unravel the role of these proteins via future experimental validation.

Addressing child health inequity through case management of under-five malaria in Nigeria: an extended cost-effectiveness analysis

BackgroundUnder-five malaria in Nigeria is a leading cause of global child mortality, accounting for 95,000 annual child deaths. High out-of-pocket medical expenditure contributes to under-five malaria mortality by discouraging care-seeking and use of effective anti-malarials in the poorest households. The significant inequity in child health outcomes in Nigeria stresses the need to evaluate the outcomes of potential interventions across socioeconomic lines.MethodsUsing a decision tree model, an extended cost-effectiveness analysis was done to determine the effects of subsidies covering the direct and indirect costs of case management of under-five malaria in Nigeria. This analysis estimates the number of child deaths averted, out-of-pocket (OOP) expenditure averted, cases of catastrophic health expenditure (CHE) averted, and cost of implementation. An optimization analysis was also done to determine how to optimally allocate money across wealth groups using different combinations of interventions.ResultsFully subsidizing direct medical, non-medical, and indirect costs could annually avert over 19,000 under-five deaths, 8600 cases of CHE, and US$187 million in OOP spending. Per US$1 million invested, this corresponds to an annual reduction of 76 under-five deaths, 34 cases of CHE, and over US$730,000 in OOP expenditure. Due to low initial treatment coverage in poorer socioeconomic groups, health and financial-risk protection benefits would be pro-poor, with the poorest 40% of Nigerians accounting for 72% of all deaths averted, 55% of all OOP expenditure averted, and 74% of all cases of CHE averted. Subsidies targeted to the poor would see greater benefits per dollar spent than broad, non-targeted subsidies. In an optimization scenario, the strategy of fully subsidizing direct medical costs would be dominated by a partial subsidy of direct medical costs as well as a full subsidy of direct medical, nonmedical, and indirect costs.ConclusionSubsidizing case management of under-five malaria for the poorest and most vulnerable would reduce illness-related impoverishment and child mortality in Nigeria while preserving limited financial resources. This study is an example of how focusing a targeted policy-intervention on a single, high-burden disease can yield large health and financial-risk protection benefits in a low and middle-income country context and address equity consideration in evidence-informed policymaking.

Antimalarial Activity of Highly Coordinative Fused Heterocycles Targeting β-Hematin Crystallization.

The β-hematin formation is a unique process adopted by Plasmodium sp. to detoxify free heme and represents a validated target to design new effective antimalarials. Most of the β-hematin inhibitors are mainly based on 4-aminoquinolines, but the parasite has developed diverse defense mechanisms against this type of chemical system. Thus, the identification of other molecular chemical entities targeting the β-hematin formation pathway is highly needed to evade resistance mechanisms associated with 4-aminoquinolines. Herein, we showed that the highly coordinative character can be a useful tool for the rational design of antimalarial agents targeting β-hematin crystallization. From a small library consisting of five compound families with recognized antitrypanosomatid activity and coordinative abilities, a group of tetradentate 1,4-disubstituted phthalazin-aryl/heteroarylhydrazinyl derivatives were identified as potential antimalarials. They showed a remarkable curative response against Plasmodium berghei-infected mice with a significant reduction of the parasitemia, which was well correlated with their good inhibitory activities on β-hematin crystallization (IC50 = 5–7 μM). Their in vitro inhibitory and in vivo responses were comparable to those found for a chloroquine reference. The active compounds showed moderate in vitro toxicity against peritoneal macrophages, a low hemolysis response, and a good in silico ADME profile, identifying compound 2f as a promising antimalarial agent for further experiments. Other less coordinative fused heterocycles exhibited moderate inhibitory responses toward β-hematin crystallization and modest efficacy against the in vivo model. The complexation ability of the ligands with iron(III) was experimentally and theoretically determined, finding, in general, a good correlation between the complexation ability of the ligand and the inhibitory activity toward β-hematin crystallization. These findings open new perspectives toward the rational design of antimalarial β-hematin inhibitors based on the coordinative character as an alternative to the conventional β-hematin inhibitors.

Antiplasmodial activity and cytotoxicity of plant extracts from the Asteraceae and Rubiaceae families

The increasing resistance of parasites to antimalarial drugs and the limited number of effective drugs are the greatest challenges in the treatment of malaria. It is necessary to search for an alternative medicine for use as a new, more effective antimalarial drug. Therefore, this study aimed to evaluate the in vitro antimalarial activity and cytotoxicity of extracts from plants belonging to the Asteraceae and Rubiaceae families. The phytoconstituents of one hundred ten ethanolic and aqueous extracts from different parts of twenty-three plant species were analyzed. Evaluation of their antimalarial activities against the chloroquine (CQ)-resistant Plasmodium falciparum (K1) strain was carried out using the lactate dehydrogenase (pLDH) assay, and their cytotoxicity in Vero cells was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric method. A total of 40.91% of the extracts were active antimalarial agents. Three extracts (2.73%) exhibited high antiplasmodial activity (IC50 < 10 μg/ml), twenty-four extracts (21.82%) were moderately active with IC50 values ranging from 10–50 μg/ml, and eighteen extracts (16.36%) were mildly active with IC50 values ranging from 50–100 μg/ml. The ethanolic leaf extract of Mussaenda erythrophylla (Dona Trining; Rubiaceae) exhibited the highest activity against P. falciparum, with an IC50 value of 3.73 μg/ml and a selectivity index (SI) of 30.74, followed by the ethanolic leaf extract of Mussaenda philippica Dona Luz x M. flava (Dona Marmalade; Rubiaceae) and the ethanolic leaf extract of Blumea balsamifera (Camphor Tree; Asteraceae), with IC50 values of 5.94 and 9.66 μg/ml and SI values of 25.36 and >20.70, respectively. GC–MS analysis of these three plant species revealed the presence of various compounds, such as squalene, oleic acid amide, β-sitosterol, quinic acid, phytol, oleamide, α-amyrin, sakuranin, quercetin and pillion. In conclusion, the ethanolic leaf extract of M. erythrophylla, the leaf extract of M. philippica Dona Luz x M. flava and the leaf extract of B. balsamifera had strong antimalarial properties with minimal toxicity, indicating that compounds from these plant species have the potential to be developed into new antiplasmodial agents.

Computational identification of Plasmodium falciparum RNA pseudouridylate synthase as a viable drug target, its physicochemical properties, 3D structure prediction and prediction of potential inhibitors.

The increased resistance to the currently effective antimalarial drugs against Plasmodium falciparum has necessitated the development of new drugs for malaria treatment. Many proteins have been predicted using various means as potential drug targets for the treatment of the P. falciparum malaria infection. Meanwhile, only a few studies went on to predict the 3-dimensional (3D) structure of potential target. Therefore, this study aimed to predict potential antimalarial drug targets against the deadliest malaria parasite P. falciparum as well as to determine the 3D structure and possible inhibitors of one of the targets. We employed machine learning approach to predict suitable drug targets in P. falciparum. Five of the predicted protein targets were considered as potential drug targets as they were non-homologous to their human counterparts. Out of these, we determined the physicochemical properties, predicted the 3D structure and carried out docking-based virtual screening of P. falciparum RNA pseudouridylate synthase, putative (PfRPuSP). The PfRPuSP was one of the potential five target proteins. Homology modelling and the ab initio methods were used to predict the 3D structure of PfRPuSP. Then, a compound library of 5621 molecules was constructed from PubChem and ChEMBL databases using 5-fluorouridine as the control inhibitor. Docking-based virtual screening was performed using Autodock 4.2 and Autodock Vina to select compounds with high binding affinity. A total of 11 compounds were selected based on their binding energies from 881 compounds which were manually examined after docking. Seven of the 11 compounds that exhibited remarkable interactions with the residues in the active sites of PfRPuSP were analysed. These compounds performed favourably when compared to the control inhibitor and predicted to bind better than 5-fluorouridine. These seven compounds are suggested as new potential lead structures for antimalarial treatment.

Antimalarial Natural Products.

Natural products have made a crucial and unique contribution to human health, and this is especially true in the case of malaria, where the natural products quinine and artemisinin and their derivatives and analogues, have saved millions of lives. The need for new drugs to treat malaria is still urgent, since the most dangerous malaria parasite, Plasmodium falciparum, has become resistant to quinine and most of its derivatives and is becoming resistant to artemisinin and its derivatives. This volume begins with a short history of malaria and follows this with a summary of its biology. It then traces the fascinating history of the discovery of quinine for malaria treatment and then describes quinine's biosynthesis, its mechanism of action, and its clinical use, concluding with a discussion of synthetic antimalarial agents based on quinine's structure. The volume then covers the discovery of artemisinin and its development as the source of the most effective current antimalarial drug, including summaries of its synthesis and biosynthesis, its mechanism of action, and its clinical use and resistance. A short discussion of other clinically used antimalarial natural products leads to a detailed treatment of other natural products with significant antiplasmodial activity, classified by compound type. Although the search for new antimalarial natural products from Nature's combinatorial library is challenging, it is very likely to yield new antimalarial drugs. The chapter thus ends by identifying over ten natural products with development potential as clinical antimalarial agents.

Level of Antimalarial Drug Utilization Amongst Teaching and Non-Teaching Staff of University of Port Harcourt, Rivers State, Nigeria

Malaria is still a threat to public health till date in all malaria endemic regions of the world. The World Health Organization (WHO) African Region continues to carry a disproportionately high share of the global malaria burden with malaria being the 2^nd leading cause of death from infectious diseases in Africa, after HIV/AIDS. Assessment of drug use patterns is becoming increasingly necessary toward promoting rational use of drugs globally. Misuse of drugs occurs in all countries and irrational practices are especially common and costly in developing countries. The study investigated the level of antimalarial drug utilization amongst Teaching and non-Teaching staff of University of Port Harcourt, Rivers State. It was a cross sectional questionnaire based study. The study assessed the knowledge, attitude and malaria preventive practices of three hundred and sixty seven (367) respondents gotten from amongst the Teaching and Non-Teaching staff of the University. SPSS version 20 was used for the analysis. Chi squared test was used to assess relationships. The study revealed that three hundred and forty four (93.7%) of the Staff frequently treated malaria with Artemisinin-based Combination Therapy (ACT) while monotherapy stood at 3.6%. Most of the Staff also had a good knowledge of symptoms of malaria and got treatment from authorized sources such as hospitals and pharmacies. Eighty six (23.4%) of the Staff do not complete the treatment regimen. The major preventive practices prevalent among the study group are covering home windows with net (91%) and spraying of insecticides (86.7%). ACTs are the most predominantly used antimalarial amongst staffers of the University. If drug utilization pattern of anti-malarial drugs is however not monitored, there is the possibility of early emergence of resistance to the highly effective anti-malarial drugs presently in use.

Investigation of &amp;lt;i&amp;gt;Plasmodium falciparum&amp;lt;/i&amp;gt; Resistance Biomarkers among Primary School Children in Western Kenya

Background: A marked decrease in malaria-related deaths worldwide has been attributed to the administration of effective antimalarials against Plasmodium falciparum. However, the continuous spread of P. falciparum resistance to anti-malarial drugs is raising a serious problem in controlling Malaria to the vulnerable children’s immune system. In recent studies, Plasmodium falciparum Kelch 13 propeller gene (Pfk13) has been reported to develop resistance to artemisinin in South Asia. In this study, we checked Plasmodium falciparum chloroquine resistance transporter gene (Pfcrt) involved in chloroquine (CQ) resistance. Method: In this study, archived 280 samples were collected from Alupe primary school children in Busia, Western Kenya from May, 2016 to November, 2016. Genomic DNA was extracted using the MightyPrep reagent. The samples were investigated for P. falciparum positivity out of which 67 of them tested positive giving a prevalence rate of 24%. The sixty-seven were subjected to PCR amplification for the molecular marker resistance to Pfcrt. After PCR amplification, the amplicons were purified and sequenced using Sanger Sequencing. The sequence data were analyzed using BioEdit software to identify point mutations. Results: 14 samples sequences were analyzed on Bioedit software giving the following amino acid changes F76C, Y66H, L70A, Y58C, T59V, V65I, P67L, T81L, Y60S, Y66S, P67T and I71F). New mutations have been reported at position 76 leading to an amino acid change, one of Pfcrt gold standard biomarkers. However, amino acid changes Y66H, L70A, Y58C, T59V, V65I, P67L, T81L, Y60S, Y66S, P67T and I71F are newly reported giving an increase in Pfcrt prevalence of concern from zero to 5.0%. A phylogenetic evolutionary relationship was constructed as shown below. Generally, the results showed a continuous resistance of P.falciparum to Pfcrt which calls for robust continuous monitoring and surveillance. Conclusion: Due to the increase of the resistant Pfcrt gene prevalence, continuous development of new mutants against chloroquine indicates that there is need to repurpose anti-malarial drugs for future partner drugs.

Artemisinin-independent inhibitory activity of Artemisia sp. infusions against different Plasmodium stages including relapse-causing hypnozoites.

Artemisinin-based combination therapies (ACT) are the frontline treatments against malaria worldwide. Recently the use of traditional infusions from Artemisia annua (from which artemisinin is obtained) or Artemisia afra (lacking artemisinin) has been controversially advocated. Such unregulated plant-based remedies are strongly discouraged as they might constitute sub-optimal therapies and promote drug resistance. Here, we conducted the first comparative study of the anti-malarial effects of both plant infusions in vitro against the asexual erythrocytic stages of Plasmodium falciparum and the pre-erythrocytic (i.e., liver) stages of various Plasmodium species. Low concentrations of either infusion accounted for significant inhibitory activities across every parasite species and stage studied. We show that these antiplasmodial effects were essentially artemisinin-independent and were additionally monitored by observations of the parasite apicoplast and mitochondrion. In particular, the infusions significantly incapacitated sporozoites, and for Plasmodium vivax and P. cynomolgi, disrupted the hypnozoites. This provides the first indication that compounds other than 8-aminoquinolines could be effective antimalarials against relapsing parasites. These observations advocate for further screening to uncover urgently needed novel antimalarial lead compounds.

The Potential use of a Curcumin-Piperine Combination as an Antimalarial Agent: A Systematic Review.

Malaria remains a significant global health problem, but the development of effective antimalarial drugs is challenging due to the parasite's complex life cycle and lack of knowledge about the critical specific stages. Medicinal plants have been investigated as adjuvant therapy for malaria, so this systematic review summarizes 46 primary articles published until December 2020 that discuss curcumin and piperine as antimalarial agents. The selected articles discussed their antioxidant, anti-inflammatory, and antiapoptosis properties, as well as their mechanism of action against Plasmodium species. Curcumin is a potent antioxidant, damages parasite DNA, and may promote an immune response against Plasmodium by increasing reactive oxygen species (ROS), while piperine is also a potent antioxidant that potentiates the effects of curcumin. Hence, combining these compounds is likely to have the same effect as chloroquine, that is, attenuate and restrict parasite development, thereby reducing parasitemia and increasing host survival. This systematic review presents new information regarding the development of a curcumin-piperine combination for future malaria therapy.

Evaluation of the Antimalarial Activity of Crude Extract of Eucalyptus globulus Labill. Leaf against Plasmodium berghei in Mice.

Introduction Traditional medicinal plants are used as a common source of developing new and effective antimalarial drugs. E. globulus leaf has been used in the traditional management of malaria in different countries, including Ethiopia. However, there is no in vivo study done on the antimalarial activity of the plant. Thus, this study aimed to evaluate the antimalarial activity of crude extract of E. globulus Labill. leaf in P. berghei-infected mice. Method The fresh leaves of E. globulus were collected, washed, air-dried, and made as coarse powder. Either sex of mice aged 6 to 8 weeks was used in the experiment. The antimalarial activity of the crude extract was tested in four-day suppressive, curative (Rane's), and prophylactic (repository) tests. The parameters like level of parasitemia, packed cell volume, body weight, rectal temperature, and mean survival time were recorded. The analysis of the data was done with SPSS version 20 with a 95% confidence interval in one-way ANOVA followed by Tukey's post hoc test. Results In all three antimalarial test models, the extract of leaf of E. globulus at all three doses suppressed the level of parasitemia significantly (p < 0.001), increased survival time (p < 0.05 to p < 0.001), and prevented a decrease in body weight as compared to the negative control. The middle and large doses of the extract also decreased loss of body temperature (p < 0.05 to p < 0.001) compared to the negative control. Reduction of packed cell volume was prevented within the three test doses of the extract in both curative and prophylactic tests and middle and large doses in the 4-day suppressive test compared to the negative control. Conclusion The crude extract of the plant showed promising antimalarial activity. This supports the traditional use and the in vitro test result of the plant.

Sintesis dan Evaluasi Antimalaria In Vitro Turunan Kinin Terhadap Plasmodium falciparum

Nowadays kinin is the most effective antimalarial drug and its used as an alternative in malaria treatment. However, toxicity of quinine restrict its use as an antimalarial drug. Lipophilicity and long half-life (t½) of quinine that reach 10-20 hours are responsible for its toxicity. The aim of this research is to obtain more polar quinine derivatives by means of hydrogen peroxide reactions to reduce the toxicity. The reactions using hydrogen peroxyde is performed analogously to the procedures reported in the literature. Extract of pure anhydrous kinin is purified in coloumn chromatography followed by structure elucidation. Synthetic product is tested in vitro against Plasmodium falciparum. The characterization of reaction products is performed with proton (1H) and carbon 13 (13C) nuclear magnetic resonance (NMR) spectroscopy. It showed that the reaction using reagents led to epoxidation of vinyl substituents of chinuclidine ring with 61,08% yields. Antimalarial test against Plasmodium falciparum obtained 1.250-2.500 μg/mL of IC50 value. The IC50 values indicated that the synthesis products were not potential for malaria treatment.

Ethnobotanical survey of anti-malarial plants used in Ilorin metropolis, Nigeria

An ethnobotanical survey of medicinal plants used in the treatment of malaria in Ilorin, Kwara State, Nigeria was carried out between March and June, 2019. Ethno-botanical data were collected by oral interview with the aid of a semi-structured questionnaire administered to forty-seven (47) herb sellers. The respondents were aware of the signs and symptoms of malaria and could readily distinguish the ailments from other feverish symptoms and conditions. Symptoms reported include body weakness, high body temperature (hot skin), loss of appetite, coldness, mouth bitterness, headache, coloured eyes (yellow), sleepless night and urine colouration (yellowish). From the study, a total of thirteen (13) plant species belonging to nine (9) families including Aannonaceae, Aapocynaceae, Rrubiaceae, Oochnaaceae were described as being used for the treatment of malaria. The plant parts used were leaves, root, stem bark and seed with roots being the most used plant part. It was also observed that recipes were made from combination of different parts from more than one plant species including bark, root and leaves while some were made from single plant part. The most preferred mode of administration was oral, while decoction and infusion were the most preferred method of preparation. However, the study observed that Picralima nitida, Enanchia chloranta and Morinda nucida were the frequently mentioned plants. Hence, these plant species could be considered as promising candidates for further scientific validation in the search for new, effective and affordable antimalarial drugs.

Efficacy of Chininum Sulphuricum 30C against Malaria: An in vitro and in vivo Study

Background: New effective, economical and safe antimalarial drugs are urgently needed due to the development of multi-drug-resistant strains of the parasite. Homeopathy uses ultra-diluted doses of various substances to stimulate autoregulatory and self-healing processes to cure various ailments. The aim of the study was to evaluate the in vitro and in vivo antimalarial efficacy of a homeopathic drug, Chininum sulphuricum 30C. Methods: In vitro antiplasmodial activity was screened against the P. falciparum chloroquine-sensitive (3D7) strain, and cell viability was assessed against normal human dermal fibroblasts and HepG2 cells. Suppressive, preventive and curative studies were carried out against P. berghei-infected mice in vivo. Results: Chininum sulphuricum (30C) revealed good antiplasmodial activity in vitro, with 92.79 ± 6.93% inhibition against the 3D7 strain. The cell viability was 83.6 ± 0.6% against normal human dermal fibroblasts and 95.22 ± 5.1% against HepG2 cells. It also exhibited suppressive efficacy with 95.56% chemosuppression on day 7 with no mortality throughout the follow-up period of 28 days. It also showed preventive activity against the disease. Drug treatment was also safe to the liver and kidney function of the host as evidenced by biochemical studies. Conclusion: Chininum sulphuricum 30C exhibited considerable antimalarial activity along with safety to the liver and kidney function of the host.

Should Deep-Sequenced Amplicons Become the New Gold Standard for Analyzing Malaria Drug Clinical Trials?

ABSTRACTRegulatory clinical trials are required to ensure the continued supply and deployment of effective antimalarial drugs. Patient follow-up in such trials typically lasts several weeks, as the drugs have long half-lives and new infections often occur during this period. “Molecular correction” is therefore used to distinguish drug failures from new infections. The current WHO-recommended method for molecular correction uses length-polymorphic alleles at highly diverse loci but is inherently poor at detecting low-density clones in polyclonal infections. This likely leads to substantial underestimates of failure rates, delaying the replacement of failing drugs with potentially lethal consequences. Deep-sequenced amplicons (AmpSeq) substantially increase the detectability of low-density clones and may offer a new “gold standard” for molecular correction. Pharmacological simulation of clinical trials was used to evaluate the suitability of AmpSeq for molecular correction. We investigated the impact of factors such as the number of amplicon loci analyzed, the informatics criteria used to distinguish genotyping “noise” from real low-density signals, the local epidemiology of malaria transmission, and the potential impact of genetic signals from gametocytes. AmpSeq greatly improved molecular correction and provided accurate drug failure rate estimates. The use of 3 to 5 amplicons was sufficient, and simple, nonstatistical criteria could be used to classify recurrent infections as drug failures or new infections. These results suggest AmpSeq is strongly placed to become the new standard for molecular correction in regulatory trials, with potential extension into routine surveillance once the requisite technical support becomes established.