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Malaria, a persistent and ancient adversary, continues to impact vast regions worldwide, afflicting millions and severely affecting human health and well‐being. Recently, despite significant progress in combating this parasitic disease, malaria remains a major global health concern, especially in areas with limited resources and vulnerable populations. Consequently, identifying and developing effective agents to combat malaria and its associated dysfunctions is essential therefore the two new Schiff base ligands incorporated Co(II), Ni(II), Cu(II) and Zn(II) ions were synthesized and thoroughly characterized. The synthesized compounds were assessed for in vitro anti‐malarial and antimicrobial efficacy, compounds (9, 10) demonstrated highest potential with IC50=1.08±0.09 to 1.18±0.04 μM against P. falciparum and MIC=0.0058 μmol/mL against C. albicans and E. coli, respectively. The complexes (5, 6) were effectively reduce mitigate oxidative stress with lowest IC50 value of 2.69±0.12 to 2.87±0.09 μM. Moreover, the biological findings were reinforced by a molecular docking investigation involving the potential compounds (2, 7–10) against dihydroorotate dehydrogenase and sterol 14‐alpha demethylase proteins which exposed complex's excellent biological response than their parent ligands. ADMET profiling was used to confirm the compounds' oral drug‐like features. This research offers promising prospects for future multi‐functional drug innovations targeting malaria, pathogenic infections, and oxidative stress. [ABSTRACT FROM AUTHOR]

Abstract Background Nigeria has the highest malaria burden globally, and anti-malarials have been commonly used to treat malaria without parasitological confirmation. In 2012, Nigeria implemented rapid diagnostic tests (RDTs) to reduce the use of anti-malarials for those without malaria and to increase the use of artemisinin-based combination therapy (ACT) for malaria treatment. This study examined changes in anti-malarial receipt among children aged 6–59 months during a 12-year period of increasing RDT availability. Methods A cross-sectional analysis was conducted using the Nigeria Malaria Indicator Survey (NMIS) data from 2010 (before RDT implementation in 2012), 2015, and 2021. The analysis assessed trends in prevalence of malaria by survey RDT result, and fever and anti-malarial/ACT receipt in the 2 weeks prior to the survey. A multivariable logistic regression was used to account for the complex survey design and to examine factors associated with anti-malarial receipt, stratified by survey RDT result, a proxy for recent/current malaria infection. Results In a nationally-representative, weighted sample of 22,802 children aged 6–59 months, fever prevalence remained stable over time, while confirmed malaria prevalence decreased from 51.2% in 2010 to 44.3% in 2015 and 38.5% in 2021 (trend test p

Hemisynthesis makes it possible to improve the activity or reduce the toxicity of a biocompound by modifying or adding peripheral groups. Catechin present in different plant species was known for its moderate anti-malarial and anti-SARS-CoV-2 activities. The aim of this work was focused on the identification of new compounds with potential anti-SARS-CoV-2 and/or anti-malarial activities, evaluated through In silico simulation. A polyphenol pharmacophore model, based on (+)-catechin (1) was virtually constructed using previously reported inhibitors. N- and/or S-heterocyclic fragments were inserted on the backbone of (+)-catechin and 12 pharmacophore hypotheses were studied. This study targeted 3 proteins biologically responsible for SARS-CoV-2 (PDB ID: 7JYC, 6M0J, and 6HZD) and one protein responsible for malaria (PDB ID: 3SRJ). Molecular docking had shown that the new catechin-aldehyde candidates have good Ligand-Protein affinity in terms of free energy compared to the study reference Narlaprevir and Artesunate for SARS-CoV-2 and malaria respectively. Theoretically, most compounds didn't show toxicity except compounds 2a, 2i, and 2k, exhibiting hepatotoxic activity. Molecular dynamics was used to prove and assess their binding stability to the target protein for each activity. The 3SRJ-2f and 6HZD-2l structures were selected for anti-malarial and anti-SARS-CoV-2 activity respectively. The 3SRJ-2f and 6HZD-2l complexes showed stable interactions to 100 ns between the inhibitor fragments and the residual amino acids of the protein. To conclude, these novel compounds are probably to become promising lead molecules for the development of effective anti-SARS-CoV-2 and/or anti-malarial of all drugs. [ABSTRACT FROM AUTHOR]

Background: Nigeria has the highest malaria burden globally, and anti-malarials have been commonly used to treat malaria without parasitological confirmation. In 2012, Nigeria implemented rapid diagnostic tests (RDTs) to reduce the use of anti-malarials for those without malaria and to increase the use of artemisinin-based combination therapy (ACT) for malaria treatment. This study examined changes in anti-malarial receipt among children aged 6–59 months during a 12-year period of increasing RDT availability. Methods: A cross-sectional analysis was conducted using the Nigeria Malaria Indicator Survey (NMIS) data from 2010 (before RDT implementation in 2012), 2015, and 2021. The analysis assessed trends in prevalence of malaria by survey RDT result, and fever and anti-malarial/ACT receipt in the 2 weeks prior to the survey. A multivariable logistic regression was used to account for the complex survey design and to examine factors associated with anti-malarial receipt, stratified by survey RDT result, a proxy for recent/current malaria infection. Results: In a nationally-representative, weighted sample of 22,802 children aged 6–59 months, fever prevalence remained stable over time, while confirmed malaria prevalence decreased from 51.2% in 2010 to 44.3% in 2015 and 38.5% in 2021 (trend test p < 0.0001). Anti-malarial use among these children decreased from 19% in 2010 to 10% in 2021 (trend test p < 0.0001), accompanied by an increase in ACT use (2% in 2010 to 8% in 2021; trend test p < 0.0001). Overall, among children who had experienced fever, 30.6% of survey RDT-positive and 36.1% of survey RDT-negative children had received anti-malarials. The proportion of anti-malarials obtained from the private sector increased from 61.8% in 2010 to 80.1% in 2021 for RDT-positive children; most of the anti-malarials received in 2021 were artemisinin-based combinations. Factors associated with anti-malarial receipt for both RDT-positive and RDT-negative children included geographic region, greater household wealth, higher maternal education, and older children. Conclusion: From 2010 to 2021 in Nigeria, both malaria prevalence and anti-malarial treatments among children aged 6–59 months decreased, as RDT availability increased. Among children who had fever in the prior 2 weeks, anti-malarial receipt was similar between children with either positive or negative survey RDT results, indicative of persistent challenges in reducing inappropriate anti-malarials uptake. [ABSTRACT FROM AUTHOR]

BACKGROUND Malaria remains one of the major causes of death worldwide. Holothuria scabra has a high nutritional content and many biological effects. The development of alternative anti-malarial drugs is necessary, considering that resistance to the newest anti-malarial drugs has been reported. This research study aimed to determine the anti-malarial effects of Holothuria scabra in mice infected with Plasmodium berghei. METHODS This was a post-test only control group study conducted on 24 Balb/c mice. Peter’s four-day suppressive test was employed to ascertain the claimed anti-plasmodial effect of the simplicia. Following inoculation with P. berghei, all 24 mice were infected and randomized into 4 groups, namely 3 treatment groups and 1 control group. The control group was given carboxymethyl cellulose, two of the treatment groups were given doses of 10 and 100 mg/kg BW Holothuria scabra, respectively, using Peter’s four-day suppressive test, while the remaining treatment group received a dose of 100 mg/kgBW using the prophylactic method. Data were analyzed using One way ANOVA. RESULTS The results showed by using both the four-day suppressive test and the prophylactic method, that Holothuria scabra has antimalarial activity. Holothuria scabra at a dose of 100 mg/kg BW was significantly effective in decreasing the percentage of parasitemia (p=0.000) and tended to inhibit the growth of Plasmodium berghei in mice (p=0.054). CONCLUSION This study demonstrated that Holothuria scabra possesses anti-plasmodial activity in mice. Hence, the sea cucumber could serve as a potential source of a newer antimalarial agent.

Abstract Background Children are particularly at risk of malaria. This analysis consolidates the clinical data for pyronaridine–artesunate (PA) paediatric granules in children from three randomized clinical trials and a real-world study (CANTAM). Methods An integrated safety analysis of individual patient data from three randomized clinical trials included patients with microscopically-confirmed Plasmodium falciparum, body weight ≥ 5 kg to

Abstract Background The lipid self-emulsifying system has been advanced as a promising delivery vehicle for improving the solubility and bioavailability of artemether and lumefantrine. However, the observed kinetic instability (propensity of lumefantrine to rapid crystallisation from nano-scale droplets) in aqueous acid has impelled some researchers to incorporate surfactants/solubilizers in the dissolution medium prior to dissolution studies. Thus, in our present work, we sought to prepare micro/large nano-scale (> 100 nm) and yet kinetically stable lumefantrine lipid self-emulsifying system (that would not require an external drug dissolution enhancing agent in the dissolution medium) and palm kernel oil-based 100 nm kinetically stable artemether lipid self-emulsifying system with rapid emulsification time. COVID-19 and Plasmodium falciparum-infected Africans with previous long exposure to malaria have manifested attenuated inflammatory cytokines more than malaria-naive patients. Therefore, the ingestion of artemether-lumefantrine with enhanced solubility may further promote blunting of cytokines. Therefore, this work was aimed at preparing ( 100 nm) lumefantrine lipid self-emulsifying system destined for improved antimalarial and anti-inflammatory activities. Results The droplet sizes of all the liquid artemether and lumefantrine formulations were between 8.95–39.88 and 1018–4195 nm, respectively. The loading efficiency for all the formulations was, between 72.91 ± 2.89 and 100.00 ± 0.29%. All the artemether and lumefantrine batches emulsified within the range of 3.90 ± 0.69 to 12.26 ± 0.69 s. Stable and transparent emulsions were formed on aqueous dilution to 1000 ml. The percentage drug released for artemether and lumefantrine ranged from 76.25 ± 2.98 to 99.22 ± 1.61%. The solid lipid self-emulsifying systems produced, had fair and passable flow properties. Differential scanning calorimetry revealed that the solid artemether and lumefantrine lipid self-emulsifying system were amorphous. Solidification with Neusilin FH2 or surfactant replacement with Kolliphor EL and Kollidon VA 64 fine prevented micro-or large nano-scale lumefantrine lipid self-emulsifying system from crystallisation in aqueous acid (pH 1.2). Higher antimalarial activity and remarkable anti-inflammatory effects (P

In the search of potential multi-target medicinal agents, new NOO-tridentate hydrazone ligands (H2L1–H2L4) (1–4) and their transition metal(II) complexes (5–20) were synthesized from salicylaldehyde derivatives and xanthene-9-carboxylic acid hydrazide. The synthesized compounds were well characterized by different techniques, such as FT-IR, (1H, 13C) NMR, mass spectrometry, UV–Vis, ESR, TG–DTA, powder-XRD, SEM-EDAX and molar conductivity measurements. The spectral techniques confirmed the tridentate nature of hydrazones and coordination of ligands with metal ion via Nazomethine, Ophenolic and Oenolic (NOO) which suggested octahedral stereochemistry of the complexes. The complexes were obtained in good yield, non-electrolytic in nature and stable up to 150 °C. The compounds (1–20) were screened for in vitro anti-malarial activity against Plasmodium falciparum 3D7 strain and the Co(II) complex (5) (IC50 = 0.94 ± 0.03 nM) exhibited comparable potency to quinine (IC50 = 0.826 ± 0.02 nM), whereas, Cu(II) complex (19) (IC50 = 0.65 ± 0.05 nM) have excellent potency to control malarial infection. Furthermore, the in vitro antimicrobial activity against six strains revealed that the compounds 5 and 19 demonstrated greater efficacy to inhibit the growth of microbial strains among the tested compounds (1–20). The most potent anti-malarial compounds (1, 5, 19) were examined by molecular docking study against Dihydroorotate dehydrogenase protein receptor (PDB ID: 1TV5) to accomplish the acquired biological results through binding energy and interaction mode. [ABSTRACT FROM AUTHOR]

The malaria parasite resides within erythrocytes during one stage of its life cycle. During this intraerythrocytic period, the parasite ingests the erythrocyte cytoplasm and digests approximately two-thirds of the host cell hemoglobin. This digestion occurs within a lysosome-like organelle called the digestive vacuole. Several proteases are localized to the digestive vacuole and these proteases sequentially breakdown hemoglobin into small peptides, dipeptides, and amino acids. The peptides are exported into the host cytoplasm via the chloroquine-resistance transporter and an amino acid transporter has also been identified on the digestive vacuole membrane. The environment of the digestive vacuole also provides appropriate conditions for the biocrystallization of toxic heme into non-toxic hemozoin by a poorly understood process. Hemozoin formation is an attribute of Plasmodium and Haemoproteus and is not exhibited by other intraerythrocytic protozoan parasites. The efficient degradation of hemoglobin and detoxification of heme likely plays a major role in the high level of replication exhibited by malaria parasites within erythrocytes. Unique features of the digestive vacuole and the critical importance of nutrient acquisition provide therapeutic targets for the treatment of malaria. [ABSTRACT FROM AUTHOR]

Background: Malaria has always been a serious infectious disease prevalent in the world. Antimalarial drugs such as chloroquine and artemisinin have been the main compounds used to treat malaria. However, the massive use of this type of drugs accelerates the evolution and spread of malaria parasites, leading to the development of resistance. A large number of related data have been published by researchers in recent years. CiteSpace software has gained popularity among us researchers in recent years, because of its ability to help us obtain the core information we want in a mass of articles. In order to analyze the hotspots and develop trends in this field through visual analysis, this study used CiteSpace software to summarize the available data in the literature to provide insights. Method: Relevant literature was collected from the Web of Science Core Collection (WOSCC) from 1 January 2015 to 29 March 2023. CiteSpace software and Microsoft Excel were used to analyze and present the data, respectively. Results: A total of 2,561 literatures were retrieved and 2,559 literatures were included in the analysis after the removal of duplicates. An irrefutable witness of the ever-growing interest in the topic of antimalarial drug resistance could be expressed by the exponentially increased number of publications and related citations from 2015 to 2022, and its sustained growth trend by 2023. During the past 7 years, USA, Oxford University, and David A Fidock are the country, institution, and author with the most publications in this field of research, respectively. We focused on the references and keywords from literature and found that the research and development of new drugs is the newest hotspot in this field. A growing number of scientists are devoted to finding new antimalarial drugs. Conclusion: This study is the first visual metrological analysis of antimalarial drug resistance, using bibliometric methods. As a baseline information, it is important to analyze research output published globally on antimalarial drug resistance. In order to better understand the current research situation and future research plan agenda, such baseline data are needed accordingly. [ABSTRACT FROM AUTHOR]

Herbal remedies are alternative option for the treatment, management, and prevention of different disease conditions such as malaria in most African communities due to their easy access and economic advantages. Heavy metals contaminations from the plant ingredients, processing or anthropogenic activities may render the herbal harmful for human consumption. Therefore, risk assessment of contaminating metals and antioxidant activities were determined in Agbo, a popular anti-malarial herbs mixture sold in Kano. The samples were collected from different locations across Kano State and labelled as A, B, C. The concentrations of some human cancer-causing (Cadmium Cd; Lead Pb and Chromium Cr) and some non-cancer-causing metals such as Copper Cu; Nickel, Ni in the sample were evaluated. The antioxidant properties were also evaluated using various assays, which include 2,2-diphenyl-2-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2) scavenging actions, Metal Chelating, phosphomolybdate test and Reducing power properties of Agbo. Some phytochemicals (Phenolic acids, flavonoids, tannins, saponins and alkaloids) were found to be present. The values predicting the probability of human developing risk of cancer ailment after the ceaseless consumption of the herbal mixtures was found higher than a standard threshold limit (>10−4) established by USEPA. While the non-cancer predicted risk index projected the Cr, Pb and Cd (from sample B) as the leading metal pollutants of the herbal mixtures posing a risk index of more than one (>1), while Ni and Pb (from sample A and C) showed a relative safe quotient. The determined IC50 value for reducing power showed the herbal mixtures exhibiting almost same antioxidant activities with sample C having the highest (IC50 6.32 μg/mL), followed by sample B (IC50 6.36 μg/mL) and sample A (IC50 6.39 μg/mL). This suggests that excess consumption of this mixtures may be generally beneficial health-wise but unsafe due to the heavy metals which could expose the consumers to probable cancer risks and other biological process distraction.

Abstract Background Coronavirus disease 2019 (COVID-19) pandemic affected malaria control activities in sub-Saharan Africa (SSA) resulting in 690,000 excess deaths in the year 2021. The authors hypothesized that COVID-19 affected the World Health Organization (WHO) Test, Treat and Track (T3) strategy that has been implemented in Uganda since 2010. In this study, health worker’s adherence to the T3 strategy during COVID-19 pandemic in Eastern Uganda was studied by assessing their knowledge, skills and practices. Methods A cross-sectional study utilizing mixed quantitative and qualitative data collections methods was conducted at Mbale Regional Referral Hospital in Eastern Uganda between November and December in 2020. Data were captured on demographics, knowledge, skills and practices for both health workers (HWs) and patients. Quantitative data were analysed using STATA 15.0 and reported as descriptive statistics, proportions and statistical associations. Moreover, qualitative data were collected via key informant interviews (KII) among purposively sampled study participants and analysed thematically using NVIVO software. Ethical approval was obtained prior to the study. Results A total of 436 study participants, of whom 103/436 (24%) and 333/436 (76%) were HWs and patients, respectively were studied. Among the HWs with mean age of 34 years (SD = 8.8 years), 81/103 (79%) had good practices, most 63/103 (61%) had good knowledge, and only 11/103 (10.7%) had good skills. Specifically, on the cadres, the laboratory personnel 19/103 (18%) had good knowledge 14/19 (74%) OR: 2.0 (95% CI 0.7–6) and were highly skilled OR: 4.6 (95% CI 1.2—18.1; P

BackgroundMalaria has always been a serious infectious disease prevalent in the world. Antimalarial drugs such as chloroquine and artemisinin have been the main compounds used to treat malaria. However, the massive use of this type of drugs accelerates the evolution and spread of malaria parasites, leading to the development of resistance. A large number of related data have been published by researchers in recent years. CiteSpace software has gained popularity among us researchers in recent years, because of its ability to help us obtain the core information we want in a mass of articles. In order to analyze the hotspots and develop trends in this field through visual analysis, this study used CiteSpace software to summarize the available data in the literature to provide insights.MethodRelevant literature was collected from the Web of Science Core Collection (WOSCC) from 1 January 2015 to 29 March 2023. CiteSpace software and Microsoft Excel were used to analyze and present the data, respectively.ResultsA total of 2,561 literatures were retrieved and 2,559 literatures were included in the analysis after the removal of duplicates. An irrefutable witness of the ever-growing interest in the topic of antimalarial drug resistance could be expressed by the exponentially increased number of publications and related citations from 2015 to 2022, and its sustained growth trend by 2023. During the past 7 years, USA, Oxford University, and David A Fidock are the country, institution, and author with the most publications in this field of research, respectively. We focused on the references and keywords from literature and found that the research and development of new drugs is the newest hotspot in this field. A growing number of scientists are devoted to finding new antimalarial drugs.ConclusionThis study is the first visual metrological analysis of antimalarial drug resistance, using bibliometric methods. As a baseline information, it is important to analyze research output published globally on antimalarial drug resistance. In order to better understand the current research situation and future research plan agenda, such baseline data are needed accordingly.

The relevance of medicinal plants as a primary source of therapeutic agents in the modern world cannot be overemphasized. Anogeissus leiocarpus (A. leiocarpus), of the family Combretaceae, is a renowned medicinal plant used in folkloric medicine for the management of various illnesses, particularly in developing countries. In African traditional medicine, the edible stem bark used as a chewing stick reportedly possesses numerous biological activities. Stem bark extract from A. leiocarpus exhibits anti-parasitic, antihypertensive, and anti-tubercular effects. Additionally, A. leiocarpus bark extract is used in traditional medicine in Sudan to alleviate cough and in Ivory Coast to treat parasitic diseases. The plant reportedly possesses other medicinal properties, including anti-diabetic, antiinflammatory, anti-malarial, and anti-cancer activities due to the presence of important phytochemicals, such as phenols, flavonoids, saponins, and alkaloids. Compounds including, serinic acid, arjungenin, isoquercetin, vitexin, kaempferol and some others have been identified as bioactives from various parts of the plant. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) pandemic affected malaria control activities in sub-Saharan Africa (SSA) resulting in 690,000 excess deaths in the year 2021. The authors hypothesized that COVID-19 affected the World Health Organization (WHO) Test, Treat and Track (T3) strategy that has been implemented in Uganda since 2010. In this study, health worker's adherence to the T3 strategy during COVID-19 pandemic in Eastern Uganda was studied by assessing their knowledge, skills and practices. Methods: A cross-sectional study utilizing mixed quantitative and qualitative data collections methods was conducted at Mbale Regional Referral Hospital in Eastern Uganda between November and December in 2020. Data were captured on demographics, knowledge, skills and practices for both health workers (HWs) and patients. Quantitative data were analysed using STATA 15.0 and reported as descriptive statistics, proportions and statistical associations. Moreover, qualitative data were collected via key informant interviews (KII) among purposively sampled study participants and analysed thematically using NVIVO software. Ethical approval was obtained prior to the study. Results: A total of 436 study participants, of whom 103/436 (24%) and 333/436 (76%) were HWs and patients, respectively were studied. Among the HWs with mean age of 34 years (SD = 8.8 years), 81/103 (79%) had good practices, most 63/103 (61%) had good knowledge, and only 11/103 (10.7%) had good skills. Specifically, on the cadres, the laboratory personnel 19/103 (18%) had good knowledge 14/19 (74%) OR: 2.0 (95% CI 0.7–6) and were highly skilled OR: 4.6 (95% CI 1.2—18.1; P < 0.0150) compared to other cadres, respectively. Among the patients whose age ranged 3 months to 80 years (mean 17.8 years) and females 177/333 (53%); a majority 257/333 (77%) were tested, of whom 139/333 (42%) tested positive. Out of the positive cases, 115/333 (35%) were treated and tracked. About 75/333 (23%) were not tested but treated for malaria. Of the 168/239 (70.3%) patients tested, 115/168 (68.5%) were positive and treated, P = 0.0001. The KII revealed low level of In-service training, overwhelming number of patients and stock-out of supplies as a key factor for poor HW adherence to T3 strategy. Conclusions: During COVID-19 pandemic period HWs adherence to T3 initiative was low as 27% malaria patients did not receive treatment. [ABSTRACT FROM AUTHOR]

Acridine derivatives have been actively researched over the years as prospective therapeutic agents for a wide range of disorders, including cancer, Alzheimer's disease and bacterial and protozoal infections. Numerous acridines with beneficial, biological or photochemical effects have been developed. More emphasis may be placed on the development of aza-acridine and other heteroatom-substituted acridine derivatives, as well as their synthesis procedures, in order to vary the type and position of the substituent on the acridine core and broaden the applicability of acridine derivatives. DNA intercalation, along with its subsequent impacts on biological processes involving DNA and related enzymes, is principally responsible for the mode of action of acridine. It is critical to investigate how acridine derivatives function in cancer treatment. Continued development of effective approaches for finding and optimising acridine derivatives for localizing at disease sites is required. Acridine medications may be used with bioactive substances such as DNA repair protein inhibitors to prevent cancer and improve results. The development of acridine derivatives with enhanced therapeutic potency and selectivity as well as luminous materials is the main topic of this review with a focus on recently designed acridine derivatives. [ABSTRACT FROM AUTHOR]

Introduction: Strychnos lucida R. Br. or Songga was empirically used as an anti-malarial and immunostimulant in the Tetun tribe, Indonesia. However, almost all plants from the genus Strychnos contain the alkaloid toxic compound strychnine. Objectives: The aims of this study are to determine in vitro/in vivo anti-malarial activity, to analyze the selectivity index, and to measure the phytoconstituents of various extracts (water, ethanol, ethyl acetate, n-hexane) from S. lucida stem. Materials and Methods: In vitro anti-malarial study was conducted against Plasmodium falciparum 3D7-chloroquine-sensitive, and in vitro cytotoxic was performed against Monkey kidney Vero cell. Plasmodium berghei ANKA-chloroquine sensitive infected malaria mice were used as a model for evaluation of in vivo anti-plasmodial. Phytoconstituents profile was determined using Thermo scientific LC-HRMS, and the m/z data was analyzed using Compound Discoverer software with mzCloud MS/MS Library. Results: Water (W), Ethanol (E), and Ethyl Acetate (EA) extract exhibited more potential in vitro/in vivo anti-malarial activity than n-hexane (H) extract (IC50 2.48±0.09; 2.45±0.02; 2.90±0.07; 7.64±0.30 μg/mL, respectively). The selectivity index of water, ethanol, ethyl acetate, and n-hexane extract are 211.47, 78.46, 249.62, and 32.39, respectively). According to the LC-HRMS profile, water and ethanol extract mainly contain alkaloid and phenolic compounds. Ethyl acetate and n-hexane mostly contain terpenoids and fatty acids. Conclusion: According to the result, we conclude that ethanol and water extract from S. lucida R. Br. display potential anti-malarial. Alkaloids and phenolic compounds probably have the most contribution to their anti-malarial activity. [ABSTRACT FROM AUTHOR]

Abstract Background Malaria is endemic in 95% of Uganda and constitutes the country’s most significant public health problem—being the leading cause of morbidity and mortality, especially among children under five years of age. The current national malaria treatment policy is to use artemisinin-based combination therapy (ACT) as first-line treatment, and recommends parasitological confirmation of malaria before therapy. Adherence to this policy, however, remains suboptimal, with the self-initiated home-based therapy being common—posing undue exposures to, and pressure on the current artemisinin-based combinations, with the danger of emergence of drug resistance. The study evaluated the anti-malarial use and its appropriateness among febrile children under five presenting to a tertiary health facility in northern Uganda in light of the current malaria treatment policy. Methods This was a cross-sectional study in a tertiary health facility in northern Uganda between March and September 2021. Children aged 6–59 months with fever were selected using systematic random sampling. A pretested interviewer-administered questionnaire was used to collect clinical data from the caregivers. Data were analysed using SPSS version 23. Descriptive statistics and multiple logistic regression models were applied. P-value

Comprehensive Summary: The structures assigned to all four members, 1—4, of the recently reported favolasin class of natural product have been prepared for the first time by chemical synthesis. Suzuki‐Miyaura cross‐coupling chemistry was used to establish the associated biaryl substructures. The key step used in preparing the 1,5‐benzodioxepin ring system associated with compounds 3 and 4 was the acid‐catalyzed 7‐exo‐tet cyclization of an appropriately substituted 2‐(oxiran‐2‐ylmethoxy)phenol while a base‐promoted 6‐exo‐tet cyclization of the same substrate was used to construct the 2,3‐dihydrobenzo[b][1,4]dioxine core of target 2. The spectral data derived from the four synthetically‐produced favolasins matched those reported for the corresponding natural products. Preliminary biological screening of compounds 1—3 as well as a suite of fourteen precursors reveal that they display no notable anti‐bacterial, anti‐fungal or anti‐tumor activities but congener K (4) is active, in the mM range, against Plasmodium falciparum. [ABSTRACT FROM AUTHOR]

Background: Malaria is endemic in 95% of Uganda and constitutes the country's most significant public health problem—being the leading cause of morbidity and mortality, especially among children under five years of age. The current national malaria treatment policy is to use artemisinin-based combination therapy (ACT) as first-line treatment, and recommends parasitological confirmation of malaria before therapy. Adherence to this policy, however, remains suboptimal, with the self-initiated home-based therapy being common—posing undue exposures to, and pressure on the current artemisinin-based combinations, with the danger of emergence of drug resistance. The study evaluated the anti-malarial use and its appropriateness among febrile children under five presenting to a tertiary health facility in northern Uganda in light of the current malaria treatment policy. Methods: This was a cross-sectional study in a tertiary health facility in northern Uganda between March and September 2021. Children aged 6–59 months with fever were selected using systematic random sampling. A pretested interviewer-administered questionnaire was used to collect clinical data from the caregivers. Data were analysed using SPSS version 23. Descriptive statistics and multiple logistic regression models were applied. P-value < 0.05 was considered for statistical significance. Results: Seventy-two (34.3%) of the 210 children with fever in this study used anti-malarials prior to the hospital visit, 29.2% (21/72) of which were on a self-medication basis, 22.2% (16/72) were empiric prescriptions—all of which inappropriate, and only 48.6% (35/72) were prescribed based on a parasitological diagnosis of malaria. The most commonly used anti-malarials were artemether-lumefantrine 60/72 (88.3%), while a lesser proportion of quinine 7/72 (9.7%), artesunate 3/72 (4.2%) and dihydroartemisinin-piperaquine 2/72 (2.8%) were used. The factors independently associated with anti-malarial use among the children with febrile illnesses were duration of fever (p = 0.001); level of the nearest facility (p = 0.027), distance from the nearest health facility (p = 0.025), and caregivers' age (p = 0.038). Conclusions: Inappropriate use of anti-malarials for childhood febrile illnesses is prevalent in the study setting, facilitated by the ease of over-the-counter access, empiric prescription and use of leftover anti-malarials. This calls for a need to address communities' health-seeking behaviour and the health providers' practice alike. [ABSTRACT FROM AUTHOR]

The Mannich reaction is one of the most broadly used organic reactions for constructing C−N and C−C bonds in synthetic chemistry. This review focuses on the multicomponent Mannich reaction and its variants for the synthesis of biologically active moieties such as anticancer, antimicrobial, antimalarial, antitubercular, anti‐inflammatory and anticonvulsant molecules. A few organocatalyzed asymmetric Mannich reactions are also incorporated. [ABSTRACT FROM AUTHOR]

Azabenzimidazoles are among the substrates most frequently found in small-molecule drugs due to their broad-spectrum biological activity. Newer drugs are continually in need of to replace existing drugs which encounter microorganism drug resistance. The reaction of 2,3-diaminopyridine precursors with variously substituted benzaldehydes has provided convenient and efficient access to a series of 4-azabenzimidazole derivatives and, regioselectively, to a series of 2-amino-5-bromo-3-(phenylimino)pyridine derivatives, while sodium cyanoborohydride reduction of the latter has afforded the corresponding 2-amino-5-bromo-3- (phenylamino)pyridine analogues. Bioassays of these and other compounds have been undertaken to explore their cytotoxicity and their activity against the parasitic protozoans, Plasmodium falciparum and Trypanosoma brucei. A number of the compounds show promising selective activity against T. brucei with IC50 values as low as 1.3 µM while two of them exhibit encouraging activity against both T. brucei and P. falciparum. [ABSTRACT FROM AUTHOR]

[Display omitted] Over the last 15 years, a small number of paediatric artemisinin-based combination therapy products have been marketed. These included Riamet® and Coartem® dispersible tablets, a combination of artemether and lumefantrine, co-developed by the Medicines for Malaria Venture and Novartis. Disappointingly, patient compliance, requirement for high-fat meal, and sporadic drug dissolution behaviours following administration still result in considerable challenges for these products. The first and foremost barrier that needs addressed for successful delivery of the artemether/lumefantrine combination is the poor solubility of lumefantrine within the gastrointestinal fluids. In this work, amorphous solid dispersions of lumefantrine within Soluplus®-based matrices have been manufactured using hot melt extrusion as a potential formulation strategy to achieve enhanced dissolution and apparent solubility. The drug loading capacity of Soluplus® to accommodate amorphous lumefantrine, whilst ensuring improved in-vitro dissolution performance, was investigated. The extrusion process employed a variety of processing parameters, including various temperature profiles and different production scales. The influence of variation in extrusion conditions upon the physical stability of manufactured amorphous solid dispersions was also examined. This allowed for a greater understanding of the role of extrusion processing conditions on the performance of supersaturated amorphous solid dispersions during dissolution and storage. This may allow for the design and manufacture of drug enabled formulations with lower drug dosing and thus a lower risk of adverse effects. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections can be associated with several cutaneous lesions, among which maculopapular rash is the most common. A maculopapular rash can also be induced by medications used for Coronavirus disease-2019 (COVID-19) treatment. The distinction between viral rash and drug eruption may be difficult especially in case of several medication use for COVID-19. Thus, this study aimed to describe cutaneous manifestations in six patients with COVID-19 and highlight clues for distinguishing SARS-CoV-2-related rash and drug eruption. Between March and June 2020, 1,492 patients were hospitalized for COVID-19 and treated with hydroxychloroquine in Marmara University Hospital. Among them, six cases were consulted for possible COVID-19-related rash or drug reaction. Hydroxychloroquine was given as monotherapy in one patient. All six patients developed an erythematous, symmetrical, and maculopapular eruption that mainly affected the trunk, axilla, and genitocrural region, 5-21 days after the onset of COVID-19 symptoms. Five patients developed rash in 4-11 days after treatment completion. Pruritus was severe. All were treated with topical corticosteroids and oral antihistamines, which provided partial relief. The resolution of the eruption was typically slow, which took a few weeks. A long period between the COVID-19 symptoms and the eruption, as well as slow recovery, is in favor of drug eruption. The effects of co-existent viral infection, a well-known promoting drug eruption factor, in facilitating adverse drug reaction in patients with COVID-19 needs further observations and research.

Abstract Background Because of the loss of chloroquine (CQ) effectiveness, the Democratic Republic of Congo (DRC)’s malaria treatment policy replaced CQ by sulfadoxine–pyrimethamine (SP) as first-line treatment of uncomplicated malaria in 2003, which in turn was replaced by artemisinin-based combination therapies (ACT) in 2005. The World Health Organization (WHO) recommends monitoring of anti-malarial drug resistance every 2 years. The study aimed to provide baseline data for biennial molecular surveillance of anti-malarial drug resistance by comparing data from a study conducted in 2019 to previously published data from a similar study conducted in 2017 in the DRC. Methods From July to November 2019, a cross-sectional study was conducted in ten sites which were previously selected for a similar study conducted in 2017 across the DRC. P. falciparum malaria was diagnosed by a rapid diagnostic test (RDT) or by microscopy and dried blood samples (DBS) were taken from patients who had a positive test. Segments of interest in pfcrt and pfk13 genes were amplified by conventional PCR before sequencing. Results Out of 1087 enrolled patients, 906 (83.3%) were PCR-confirmed for P. falciparum. Like in the 2017-study, none of the mutations known to be associated with Artemisinine (ART) resistance in Southeast Asia was detected. However, non-synonymous (NS) mutations with unknown functions were observed among which, A578S was detected in both 2017 and 2019-studies. The overall prevalence of pfcrt-K76T mutation that confers CQ-resistance was 22.7% in 2019-study compared to 28.5% in 2017-study (p-value = 0.069), but there was high variability between sites in the two studies. Like in 2017-study, the pfcrt 72–76 SVMNT haplotype associated with resistance to amodiaquine was not detected. Conclusion The study reported, within 2 years, the non-presence of molecular markers currently known to be associated with resistance to ART and to AQ in P. falciparum isolated in the DRC. However, the presence of polymorphisms with as-yet unknown functions was observed, requiring further characterization. Moreover, an overall decrease in the prevalence of CQ-resistance marker was observed in the DRC, but this prevalence remained highly variable from region to region.

Introduction: Dihydroartemesinin is a hydrophobic anti-malarial having solubility less than 0.1 g/L. In order to improve its solubility a self emulsifying drug delivery system for dihydroartemesinin has been developed. Material and method: The formulation containing Dihydroartemesinin, Groundnut Oil, Cremephor RH and Tween 80 was prepared. The excipients selected, were based upon their solubilities in different oils, surfactants and cosurfactants. Self-micro emulsification time, zeta potential, droplet size, poly dispersity index, transmission electron microscopy, drug release and in-vivo studies were performed for characterization. Result: The prepared formulation has globule size of 16.59±0.40 nm and zeta potential -10.75±1.18 mV. The in vitro dissolution performance of dihydroartemesinin was found to be good andshowed significantly (p<0.05, Origin Pro 8.5) higher drug release when compared with pure drug over a period of 120 minutes. In vivo studies in mice revealed that the cure rate of parasitemia increased by the use of prepared formulationin comparison to pure drug. Conclusion: The lower dosages, i.e. 30 and 20mg/kg, provided 80 percent cure till the observation period as compared to the pure drug which showed only 20 percent cure rate at the same dose. [ABSTRACT FROM AUTHOR]

Three-dimensional quantitative structure-activity relationships were studied on 35 natural aurone derivatives by the Topomer CoMFA method to establish the 3 D-QSAR models, and exerting potent affections as Qo site inhibitors in cytochrome b activity for anti-malaria. The cross-validated q2 value of the Topmer CoMFA model = 0.539, the non-cross-validated r2 = 0.793, r pred 2 = 0.960, which revealed the model has good stability and predictability. The steric and electrostatic field visualization provided by the Topomer CoMFA model intuitively revealed the effects of different substituent structures. Using this information for molecule design, we theoretically obtained some new aurone derivatives as antimalarial drugs with higher activity. Furthermore, molecular docking was employed to explore the binding requirements between the ligands and the receptor protein. We obtained space relations by hydrogen bonds and hydrophobic interactions between aurone derivatives and the active site residues. The observations from these QSAR and molecular docking studies can be further used to design promising antimalarial drugs. [ABSTRACT FROM AUTHOR]

Most of the currently marketed drugs consist of heterocyclic scaffolds containing nitrogen and or oxygen as heteroatoms in their structures. Several research groups have synthesized diversely substituted 1,2,4-oxadiazoles as anti-infective agents having anti-bacterial, anti-viral, anti-leishmanial, etc. activities. For the first time, the present review article will provide the coverage of synthetic account of 1,2,4-oxadiazoles as anti-infective agents along with their potential for SAR, activity potential, promising target for mode of action. The efforts have been made to provide the chemical intuitions to the reader to design new chemical entity with potential of anti-infective activity. This review will mark the impact as the valuable, comprehensive and pioneered work along with the library of synthetic strategies for the organic and medicinal chemists for further refinement of 1,2,4-oxadiazole as anti-infective agents. [ABSTRACT FROM AUTHOR]

Abstract Background Since 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and molecular markers of anti-malarial resistance. Methods Children aged six months to 14 years with uncomplicated falciparum malaria and a parasitaemia of 1000–100,000 parasites/µl determined by microscopy were enrolled from May–September 2018 in a 28-day in vivo trial using the 2009 World Health Organization protocol for monitoring anti-malarial efficacy. Participants from two communes, Ankazomborona (tropical, northwest) and Matanga (equatorial, southeast), were randomly assigned to ASAQ or AL arms at their respective sites. PCR correction was achieved by genotyping seven neutral microsatellites in paired pre- and post-treatment samples. Genotyping assays for molecular markers of resistance in the pfk13, pfcrt and pfmdr1 genes were conducted. Results Of 344 patients enrolled, 167/172 (97%) receiving ASAQ and 168/172 (98%) receiving AL completed the study. For ASAQ, the day-28 cumulative PCR-uncorrected efficacy was 100% (95% CI 100–100) and 95% (95% CI 91–100) for Ankazomborona and Matanga, respectively; for AL, it was 99% (95% CI 97–100) in Ankazomborona and 83% (95% CI 76–92) in Matanga. The day-28 cumulative PCR-corrected efficacy for ASAQ was 100% (95% CI 100–100) and 98% (95% CI 95–100) for Ankazomborona and Matanga, respectively; for AL, it was 100% (95% CI 99–100) in Ankazomborona and 95% (95% CI 91–100) in Matanga. Of 83 successfully sequenced samples for pfk13, no mutation associated with artemisinin resistance was observed. A majority of successfully sequenced samples for pfmdr1 carried either the NFD or NYD haplotypes corresponding to codons 86, 184 and 1246. Of 82 successfully sequenced samples for pfcrt, all were wild type at codons 72–76. Conclusion PCR-corrected analysis indicated that ASAQ and AL have therapeutic efficacies above the 90% WHO acceptable cut-off. No genetic evidence of resistance to artemisinin was observed, which is consistent with the clinical outcome data. However, the most common pfmdr1 haplotypes were NYD and NFD, previously associated with tolerance to lumefantrine.

Cryptolepis sanguinolenta is an important medicinal plant used in the treatment of malaria in Ghana. Overharvesting, destruction of entire plant populations and poor seed viability have resulted in a substantial decrease in wild populations thereby threatening its long-term potential and survivability. In this study, fifteen polymorphic microsatellite loci were used to evaluate the genetic diversity and population structure of 179 C. sanguinolenta individuals among eight subpopulations in Ghana. The subpopulations were separated by a distance of 8.3 – 233.3 km. Our results indicated relatively high levels of genetic diversity (Ho= 0.41; He=0.61) and high gene flow (Nm=7.06), an indication of greater stability and adaptability within the ecosystem, limited genetic differentiation (mean FST=0.05; highest FST=0.1), which suggested insignificant differentiation among the subpopulations. The high levels of gene flow resulting from the wind-dispersed seeds might have contributed to the limited genetic differentiation among the subpopulations. The Bayesian cluster analysis revealed the presence of a population structure (K=2). A lack of isolation by distance (r=0.012; P=0.34) indicated an increase in the genetic similarity among the subpopulations as the geographic distance between them decreased. This study described the genetic diversity and population structure in the current C. sanguinolenta accessions and laid a foundation for future breeding efforts.

Quinoxaline is a nitrogen-containing heterocyclic compound having many pharmaceutical and industrial purposes. It can be synthesized by adopting green chemistry principles. The quinoxaline containing drugs such as Olaquindox, Echinomycin, Atinoleutin, Levomycin, and Carbadox are currently used as an antibiotic in the market. The objective of this review is to enumerate the various multifunctional property of the quinoxaline moiety. This present review contains the newer quinoxaline derivatives against many targets, receptors, or microorganisms. This work comprises the study on quinoxaline as a core unit from the year 2002 to 2020. All the collected literature has been combined and highlighted for the effective use of that particular derivative. Various potent quinoxaline compounds have been analyzed in the literature. About 50 papers have been reviewed for the novel quinoxaline compounds, the potent derivatives have been reported, and structures were given. The critical role of the quinoxaline on the various heterocyclic moieties has been given more attention in this review. This review paves the way as a source of references for the further development of drug discovery in the wide spectrum of its biological importance. [ABSTRACT FROM AUTHOR]

Despite much interest and studies toward the genus Podocarpus, the anti-malarial evaluation of Podocarpus polystachyus's phytoconstituents remains lacking. Herein, the phytoconstituents of P. polystachyus leaves and their anti-malarial effect against Plasmodium falciparum were investigated for the first time. One new natural product, 8ß,13ß-kaur-15-en-17-al (1), along with three known compounds, 8ß,13ß-kaur-15-en-17-ol (2) and 13ß-kaur-16-ene (3), and α-tocopherol hydroquinone (4) were isolated via HR-ESI-MS and NMR analyses. Compounds 1 and 2 inhibited P. falciparum growth at 12 and 52 µM of IC50, respectively. Their anti-malarial activity was associated with the in silico P. falciparum lactate dehydrogenase (PfLDH) inhibition. Molecular docking of ligands 1 and 2 with the putative target PfLDH revealed ~−2 kcal/mol of binding energies more negative than the control. Molecular dynamic simulations (100 ns) showed equal or smaller deviation values (RMSD, RMSF, Rg) and stronger interactions of PfLDH-1 and PfLDH-2 complexes via at least one consistent H-bond than the control. Additionally, a slightly increased PfLDH H-bond profile in their interactions improved the PfLDH dynamic and structural stabilities. Overall, this study supports the relevance of 1 and 2 as plasmodial growth inhibitors with their putative anti-PfLDH activity, which could be a potential scaffold for developing anti-malarial drugs. [ABSTRACT FROM AUTHOR]

Dagninet Derebe,1 Muluken Wubetu,2 Amare Alamirew3 1Department of Pharmacy, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia; 2Department of Pharmacy, College of Health Sciences, Debre Markos University, Debre Markos, Ethiopia; 3Department of Community Health, ALKAN Health Science, Business and Technology College, Bahir Dar, EthiopiaCorrespondence: Dagninet Derebe Email dagninet37@yahoo.comBackground: Due to resistance of parasites, costs, and safety issues with currently available drugs, there is a need to discover new antimalarials. Medicinal plants are one of the most important sources of new drugs. The purpose of this study was to evaluate the antimalarial activity of a methanolic root extract of Dorstenia barnimiana in Swiss albino mice infected with Plasmodium berghei.Methods: Four-day suppressive, curative, and prophylactic tests were performed on mice infected with P. berghei to evaluate the antimalarial activity of a methanolic root extract of the plant. Parasitemia suppression, survival time, body-weight change, rectal temperature change, and packed-cell volume were used to evaluate the activity of the extract. Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test for comparisons between and within groups, with P< 0.05 considered statistically significant.Results: The D. barnimiana root extract showed significant (P< 0.01) parasitemia-suppressive activities in all models compared to the negative control. The extract increased mean survival time and prevented weight loss, reduction in temperature, and anemia significantly in all tested doses in 4-day suppressive and curative tests.Conclusion: Based on these findings, D. barnimiana root has promising antimalarial activity and can considered a potential source to develop new agents.Keywords: antimalarial, Dorstenia barnimiana, Plasmodium berghei, 4-day suppressive test, curative test, prophylactic test

Herbal medicines contain single herb or many herbal ingredients derived from the plant and their byproducts. The beneficial effects of medicinal plants in the healthcare system are mainly due to the presence of secondary metabolites which have numerous biological applications in medicine. Chrysosplenetin is a polymethoxylated flavonoid class phytochemical found to be present in Artemisia annua L. and Dracocephalum heterophyllum Benth. Scientific research data of chrysosplenetin has been collected from various literature databases in the present work and analyzed for their medicinal properties and pharmacological activities. Medicinal importance and pharmacological activity data of chrysosplenetin has been collected from Google, Science Direct, PubMed, and Scopus and analyzed in the present work to know the therapeutic benefit of chrysosplenetin. However, the analytical data of chrysosplenetin has been also collected and analyzed in the present work to know the importance of modern analytical techniques in the separation, isolation, and identification of chrysosplenetin. Scientific data analysis of collected research work from various literature databases revealed the biological importance of chrysosplenetin in medicine. Pharmacological data of chrysosplenetin revealed the anti-malarial, antiproliferative, and antibacterial effect of chrysosplenetin. Chrysosplenetin has a significant effect on bone loss, enterovirus 71, trichomoniasis, tyrosinase enzyme, multidrug resistance, inflammatory, and neurological disorders. Pharmacokinetic parameters of chrysosplenetin have been also studied in the present work. Literature data analysis signified the potential role of different analytical techniques in medicine for their isolation, separation, and quantification. Scientific data analysis of the collected data of chrysosplenetin in the present work signified the therapeutic benefit of chrysosplenetin in medicine for the treatment of numerous diseases and associated complications.

Abstract Background The national policy for malaria treatment of the Democratic Republic of Congo recommends two first-line artemisinin-based combinations for the treatment of uncomplicated malaria: artesunate-amodiaquine and artemether-lumefantrine. This study investigated the presence of markers associated with resistance to the current first-line artemisinin-based combination therapy (ACT) in isolates of Plasmodium falciparum from treatment failure patients in the Democratic Republic of Congo. Methods From November 2018 to November 2019, dried blood spots were taken from patients returning to health centres for fever within 28 days after an initial malaria treatment in six sentinel sites of the National Malaria Control Programme across Democratic Republic of Congo. The new episode of malaria was first detected by a rapid diagnostic test and then confirmed by a real-time PCR assay to define treatment failure. Fragments of interest in pfk13 and pfcrt genes were amplified by conventional PCR before sequencing and the Pfmdr1 gene copy number was determined by a TaqMan real-time PCR assay. Results Out of 474 enrolled patients, 364 (76.8%) were confirmed positive by PCR for a new episode of P. falciparum malaria, thus considered as treatment failure. Of the 325 P. falciparum isolates obtained from 364 P. falciparum-positive patients and successfully sequenced in the pfk13-propeller gene, 7 (2.2%) isolates carried non-synonymous mutations, among which 3 have been previously reported (N498I, N554K and A557S) and 4 had not yet been reported (F506L, E507V, D516E and G538S). Of the 335 isolates successfully sequenced in the pfcrt gene, 139 (41.5%) harboured the K76T mutation known to be associated with chloroquine resistance. The SVMNT haplotype associated with resistance to amodiaquine was not found. None of the isolates carried an increased copy number of the pfmdr1 gene among the 322 P. falciparum isolates successfully analysed. Conclusion No molecular markers currently known to be associated with resistance to the first-line ACT in use were detected in isolates of P. falciparum from treatment failure patients. Regular monitoring through in vivo drug efficacy and molecular studies must continue to ensure the effectiveness of malaria treatment in Democratic Republic of Congo.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections can be associated with several cutaneous lesions, among which maculopapular rash is the most common. A maculopapular rash can also be induced by medications used for Coronavirus disease-2019 (COVID-19) treatment. The distinction between viral rash and drug eruption may be difficult especially in case of several medication use for COVID-19. Thus, this study aimed to describe cutaneous manifestations in six patients with COVID-19 and highlight clues for distinguishing SARS-CoV-2-related rash and drug eruption. Between March and June 2020, 1,492 patients were hospitalized for COVID-19 and treated with hydroxychloroquine in Marmara University Hospital. Among them, six cases were consulted for possible COVID-19-related rash or drug reaction. Hydroxychloroquine was given as monotherapy in one patient. All six patients developed an erythematous, symmetrical, and maculopapular eruption that mainly affected the trunk, axilla, and genitocrural region, 5-21 days after the onset of COVID-19 symptoms. Five patients developed rash in 4-11 days after treatment completion. Pruritus was severe. All were treated with topical corticosteroids and oral antihistamines, which provided partial relief. The resolution of the eruption was typically slow, which took a few weeks. A long period between the COVID-19 symptoms and the eruption, as well as slow recovery, is in favor of drug eruption. The effects of co-existent viral infection, a well-known promoting drug eruption factor, in facilitating adverse drug reaction in patients with COVID-19 needs further observations and research. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the antimalarial activity of active fractions from Alectryon serratus leaves and identify their secondary metabolites. Methods: Fractionation of ethyl acetate fraction from Alectryon serratus leaves was conducted using column chromatography. Five serial concentrations (10, 1, 0.1, 0.01 and 0.001 µg/mL) of each subfraction were tested in vitro against Plasmodium falciparum 3D7 (chloroquine-sensitive). The active subfractions were separated using preparative TLC. Crude isolates were administrated to P. falciparum culture and incubated for 48 h. The percentages of growth inhibition and IC50 were calculated. Secondary metabolites group of sub-fractions and the crude isolate were determined using TLC, FTIR, and UV-VIS spectrophotometry. Chloroquine was used as a standard drug for antiplasmodial testing. Results: Four sub-fractions, ETA.4, ETA.8, ETA.9 and ETA.11, exhibited antimalarial activity with IC50 values at 0.035, 0.187, 0.015 and 0.017 µg/mL. Sub-fractions ETA.11 separated using preparative TLC yielded ETA.11.1 and ETA.11.2. Sub-fractions ETA.11.1 and ETA.11.2 showed antimalarial activity with IC50 values at 0.011 and 0.01 µg/mL. The TLC chromatogram of active sub-fractions showed flavonoids and phenolic. Conclusion: Crude isolates ETA.11.1 and ETA.11.2 contain flavonoid compounds and have potential antiplasmodial activity. [ABSTRACT FROM AUTHOR]

Abstract Background Tafenoquine is an 8-aminoquinoline anti-malarial drug recently approved as a single-dose (300 mg) therapy for Plasmodium vivax relapse prevention, when co-administered with 3-days of chloroquine or other blood schizonticide. Tafenoquine 200 mg weekly after a loading dose is also approved as travellers’ prophylaxis. The development of tafenoquine has been conducted over many years, using various dosing regimens in diverse populations. Methods This review brings together all the preclinical and clinical data concerning tafenoquine central nervous system safety. Data were assembled from published sources. The risk of neuropsychiatric adverse events (NPAEs) with single-dose tafenoquine (300 mg) in combination with chloroquine to achieve P. vivax relapse prevention is particularly examined. Results There was no evidence of neurotoxicity with tafenoquine in preclinical animal models. In clinical studies in P. vivax relapse prevention, nervous system adverse events, mainly headache and dizziness, occurred in 11.4% (36/317) of patients with tafenoquine (300 mg)/chloroquine versus 10.2% (19/187) with placebo/chloroquine; and in 15.5% (75/483) of patients with tafenoquine/chloroquine versus 13.3% (35/264) with primaquine (15 mg/day for 14 days)/chloroquine. Psychiatric adverse events, mainly insomnia, occurred in 3.8% (12/317) of patients with tafenoquine/chloroquine versus 2.7% (5/187) with placebo/chloroquine; and in 2.9% (14/483) of patients with tafenoquine/chloroquine versus 3.4% (9/264) for primaquine/chloroquine. There were no serious or severe NPAEs observed with tafenoquine (300 mg)/chloroquine in these studies. Conclusions The risk:benefit of single-dose tafenoquine/chloroquine in P. vivax relapse prevention is favourable in the presence of malaria, with a low risk of NPAEs, similar to that seen with chloroquine alone or primaquine/chloroquine.

Herein, we report the anti-malarial, anti-bacterial and anti-inflammatory activities of the N 2 O 2 donor tetradentate salen type ligand and its CoL, NiL, and CuL metal complexes. The synthesized compounds were characterized by various spectroscopic analytical methods. The in-vitro anti-malarial investigations revealed that the complex CuL exhibited equipotency with quinine drug having IC 50 value 0.25 μg/mL. The compound L showed significant inhibition of bacterial spp. viz. E. Coli, P. Aeruginosa, and S. Aureus (MIC=12.5-50 μg/mL), while the compound CoL (MIC=12.5 μg/mL) exhibited potency against gram-positive bacteria. In the in-vitro anti-inflammatory study, the compound CuL displayed moderate activity than other tested compounds. The compound CuL showed the highest anti-malarial docking score with enzyme pLDH at -8.12 Kcal/mol. The DFT study also gives authentication of higher antimalarial activity of CuL due to high dipole moment. None of the potent compounds was found cytotoxic towards vero cell lines., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Since 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and molecular markers of anti-malarial resistance. Methods: Children aged six months to 14 years with uncomplicated falciparum malaria and a parasitaemia of 1000–100,000 parasites/µl determined by microscopy were enrolled from May–September 2018 in a 28-day in vivo trial using the 2009 World Health Organization protocol for monitoring anti-malarial efficacy. Participants from two communes, Ankazomborona (tropical, northwest) and Matanga (equatorial, southeast), were randomly assigned to ASAQ or AL arms at their respective sites. PCR correction was achieved by genotyping seven neutral microsatellites in paired pre- and post-treatment samples. Genotyping assays for molecular markers of resistance in the pfk13, pfcrt and pfmdr1 genes were conducted. Results: Of 344 patients enrolled, 167/172 (97%) receiving ASAQ and 168/172 (98%) receiving AL completed the study. For ASAQ, the day-28 cumulative PCR-uncorrected efficacy was 100% (95% CI 100–100) and 95% (95% CI 91–100) for Ankazomborona and Matanga, respectively; for AL, it was 99% (95% CI 97–100) in Ankazomborona and 83% (95% CI 76–92) in Matanga. The day-28 cumulative PCR-corrected efficacy for ASAQ was 100% (95% CI 100–100) and 98% (95% CI 95–100) for Ankazomborona and Matanga, respectively; for AL, it was 100% (95% CI 99–100) in Ankazomborona and 95% (95% CI 91–100) in Matanga. Of 83 successfully sequenced samples for pfk13, no mutation associated with artemisinin resistance was observed. A majority of successfully sequenced samples for pfmdr1 carried either the NFD or NYD haplotypes corresponding to codons 86, 184 and 1246. Of 82 successfully sequenced samples for pfcrt, all were wild type at codons 72–76. Conclusion: PCR-corrected analysis indicated that ASAQ and AL have therapeutic efficacies above the 90% WHO acceptable cut-off. No genetic evidence of resistance to artemisinin was observed, which is consistent with the clinical outcome data. However, the most common pfmdr1 haplotypes were NYD and NFD, previously associated with tolerance to lumefantrine. [ABSTRACT FROM AUTHOR]

Malaria, a parasitic disease, is one of the major causes of morbidity and mortality, particularly in the tropics. Following the increased resistance of the primary causative parasite, Plasmodium sp, to the mainstream drug, artemisinin combination therapies (ACTs), combating malaria incidences, morbidity and mortality have remained elusive. Novel pyrano-benzodioxepin derivatives (DHA-PABA and DHA-LEVO) were synthesized and characterized using Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopies. The compounds were subjected to standard in vivo antimalarial screening (using chloroquine-sensitive strain) in mice, and the toxicity was also determined using a standard assay. The observed elevation in serum alkaline phosphatase and acid phosphatase activity in the untreated and the group administered lower doses of DHA-LEVO is an indication of the hepatic stage of the parasite in the experimental animal, which is accompanied by significant perturbation in the membrane of the hepatocyte leading to leakage of this enzyme out of the liver cells. The semisynthetic pyrano-benzodioxepin derivatives act rapidly by clearing the parasite load from the blood. The novel pyrano-benzodioxepin candidates containing endoperoxide functionality hold promise in the pursuit of new monotherapy drug candidates against the virulent strain of the plasmodium.

A novel series of liquid crystals involving cinnamate-based mesogenic units interlinked between aromatic ester and alkyl bromide were designed and synthesized. All target molecules were confirmed by IR, 1H NMR, 13C NMR, ESI-MS, and elemental analysis. The mesomorphic behavior of novel synthesized materials (P1–P18), (V1–V18), and (M1–M18) was investigated through a polarizing optical microscope, differential scanning calorimetry, and thermogravimetric analysis (TGA) analysis. The lower carbon chain substituted member showed nematic phase while compound possess higher carbon chain exhibited only SmC phase. Thermal stability is determined by TGA analysis. All the cinnamate derivatives were screened for their anti-microbial, anti-malarial, and anti-tuberculosis potency. Among them, most of the derivatives exhibited outstanding anti-bacterial and anti-tuberculosis activity. Some derivatives also exhibited potent anti-fungal activity. [ABSTRACT FROM AUTHOR]

Abstract Background The influx of substandard and falsified medicines is a global public health challenge and its rapid detection is a key solution to the menace. This study used three screening methods and one confirmatory method for the quality assessment of 25 batches of artemether/lumefantrine dosage forms from the Ghanaian market to test that combined screening methods only can rapidly detect substandard and/or falsified medicines in areas where confirmatory methods may not be available. Methods The quality of artemether/lumefantrine tablet products obtained from pharmacies and licensed chemical seller shops within the Accra metropolis in Ghana were analysed using three screening methods (GPHF Minilab, Colorimetry and Counterfeit Drug Indicator) and one confirmatory method (high-performance liquid chromatography). Results The results showed that 18/25 batches of the artemether/lumefantrine samples passed using the combined screening and confirmatory methods and 5/25 batches of the artemether/lumefantrine samples failed using the combined screening and confirmatory methods. However, 1/25 batch of the artemether/lumefantrine samples failed using the combined screening methods but passed using the confirmatory method. Also, 1/25 batch of the artemether/lumefantrine samples passed using the combined screening methods but failed using the confirmatory method. This notwithstanding, the combined screening methods and the confirmatory method provided equivalent quality assessment profiles for 23/25 (92%) batches of the artemether/lumefantrine tablet products. Out of the 6 samples that failed the confirmatory test, 1/6, 2/6, and 3/6 failed on the high (> 110%), low (

Today more than ever, mosquito-borne diseases have a major influence on the quality of life and socio-economic development of a large part of the human population. Malaria is one such diseases. Responsible for reaching almost half of the world's population in about 100 countries, its occurrence has a tremendous impact on the human health of 214 million people, being the cause of the death of more than 438 000 people, and, also, to significant economic losses. Recent increases in drug resistance (drugs and repellents) and climate change, have led this disease to spread into new geographical areas, especially in Europe’s outskirts. Aware of this situation, the authors sought to develop a new biodegradable and antimalarial technological solution, through the functionalization of PLA filaments. It is expected that, this new technological solution, might contribute to the diminishing of the impact of malaria on human health. Bearing this purpose in mind, this researcg work aim at the development of a new piece of cloth made with an entirely new family of PLA fibres, specifically designed. Those fibres were embedded with internally developed microcapsules containing a natural repellent agent – schinus molle – added during the extrusion process. Based upon this new fibre, three knit structures were produced and the repellent efficacy and washing resistance were assessed.

Abstract Background The present study aimed to evaluate the management of severe malaria at Gezira State hospitals in Sudan by assessing hospital readiness, health care provider knowledge and the care received by severe malaria patients. Methods A cross-sectional descriptive study was performed to assess the severe malaria management practices at hospitals level in Gezira State. The study population included hospitals, health care providers and patients. Data was collected using checklists and structured questionnaires. Results A total of 20 hospitals, 158 health care providers and 370 patients were included in the study. Out of the total hospitals, 95% (19/20) were providing 24 h outpatient services, 65% (13/20) had ICU units, while triage system was found in only 35% (7/20) of hospitals. From all hospitals evaluated, 90% (18/20) were suffering from shortage of staff, especially doctors. About half of the health care providers (46.7%) did not receive severe malaria management training. The average knowledge score among health care providers was 55.4%. Microscopy was available in all hospitals (100%), while rapid diagnostic test, complete blood count and renal function test were available in 15 hospitals (75%). Fever was the most presenting symptom (97.8%) followed by repeated vomiting (51.4%), convulsion in children (24.3%) and prostration in adult (57.9%). Correctly diagnosed patients were 68.9%. Essential tests were done for only 11.1% of patients. Majority of patients (91.7%) were treated with quinine, 5.9% received artemether, while 2.4% were treated with artemether–lumefantrine. Those who received both the correct dose and dosing regimen were 53.8%. The overall compliance to guidelines was 2.2%. Conclusion This study highlights the fact that management of severe malaria at hospital level was suboptimal with serious shortcomings in the different aspects of care particularly in specialized hospitals. Technical staff was inadequate, hospitals were anguish from defective emergency services, and most patients were not treated according to the national guidelines.