Malaria Therapy Research Articles

Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in Plasmodium berghei-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling

Objectives: Investigating how nanoparticle systems interact in whole blood (WB) is critical to evaluating the effectiveness of malaria therapy. Methods: We decided to establish a pharmacokinetic/pharmacodynamic (PK/PD) model of the quinine population in WB using Plasmodium berghei-infected mice, with a subsequent model comparison for nanocapsules coated with polysorbate (NCP80) or prepared with Eudragit® RS (NCEUD). The WB quinine population pharmacokinetic model in rats was developed using plasma and partition coefficients for rat erythrocytes. Mouse WB quinine population PK/PD modeling was developed using allometrically scaled literature-free mouse quinine pharmacokinetic data and covariate values to obtain a WB population pharmacokinetic model for quinine and nanocapsules in mice. This allowed for PK/PD modeling of the quinine population with the WB concentration and parasitemia data in mice. All models were built in NONMEN. Results: The WB quinine concentration profiles in rats were characterized using a two-compartment model. Nanoencapsulation reduced clearance and central compartment volume and increased peripherical compartimental volume. A maximum effect model described the PK/PD of the quinine WB population in mice, demonstrating that NCEUD enhances the antimalarial effect. Conclusions: Quinine WB is a good surrogate for describing the response to exposure in malaria. NCEUD outperformed NCP80 and free quinine, suggesting that cationic surfaces improve the potential for treating malaria.

Unraveling Cordia myxa’s anti-malarial potential: integrative insights from network pharmacology, molecular modeling, and machine learning

Malaria is a potentially fatal infective illness caused due to parasites that belong to the Plasmodium genus, which are transferred to humans with the help of the stings of affected female Anopheles mosquitoes, and it persists as a serious public wellness problem worldwide. Cordia myxa is a medicinal plant that possesses various medicinal characteristics like antimicrobial, anti-inflammation, antioxidant, and antidiabetic activities, which makes it an important natural resource for the therapy of different maladies in traditional medicine. In this investigation, a certain network pharmacology method has been utilized to identify the potent active components, possible targets as well as signaling pathways present in C. myxa in relation to malaria therapy. The active compounds were submitted to molecular docking approaches to validate their successful activity against the potential targets. The study concluded that three constituents named cosmosiin, stigmastanol, robinetin, and quercetin were highly active and could regulate the expression of Interleukin 6 (IL6) and Cysteine-aspartic acid protease 3 (CASP3), which may act as a potential therapeutic target for malaria treatment. These analyses are validated by molecular dynamics simulation which reflects on the overall structural stability of the intermolecular conformation and interactions. These results can also be witnessed in simulation-based trajectories binding free energies, which concluded the significant role of electrostatic and van der Waals energies in total intermolecular interactions. Finally, we utilized machine learning to predict the anti-malarial activity of C. myxa compounds, comparing them with approved drugs. Using the Chemprop model and MAIP predictions, we assessed ten compounds, revealing their potential as lead anti-malarial agents. This study establishes a groundwork for comprehending the function of the anti-malaria action of C. myxa.

Post Artesunate Delayed Hemolysis in Pediatric Patients in the United States

Abstract Background Malaria continues to pose a major threat to global public health, causing millions of infections and hundreds of thousands of deaths each year. Intravenous artesunate is the current first line therapy for severe malaria and has substantially reduced its mortality. Some patients develop severe delayed hemolysis after artesunate therapy, a phenomenon termed post artesunate delayed hemolysis (PADH). A recent study of U.S. adults treated with artesunate found that 2.7% of patients experienced PADH and 56% of those patients required blood transfusion. Thus, the U.S. Food and Drug Administration recommends that patients treated with artesunate receive weekly post-treatment monitoring of hemoglobin and hemolytic markers for four weeks after therapy. While PADH in adults frequently requires blood transfusion, the frequency and severity of PADH in pediatric patients in non-endemic countries is not known. Understanding the risk of PADH in pediatric patients is essential to determine appropriate monitoring for this condition. Methods Multicenter Retrospective Chart Review To estimate rates of PADH in pediatric patients (0-18 years of age), we used ICD-10 diagnosis codes to identify patients treated for malaria at seven hospitals (The Children’s Hospital of Philadelphia, Riley Hospital for Children, Texas Children’s Hospital, Seattle Children’s Hospital, UCSF Benioff Children’s Hospital, NYU Langone Medical Center, and Bellevue Hospital), between April 2017 and July 2022. We reviewed post-discharge laboratory values and clinic visits to identify patients with laboratory findings of PADH and determine clinical outcomes. Pediatric Health Information System (PHIS) Database Review To estimate rates of severe PADH requiring repeat emergency room visit or hospitalization, we used ICD-10 diagnosis codes to identify patients who were treated for malaria with artesunate between January 2019 and July 2023 in a database of 49 children’s hospitals (PHIS). We reviewed patient visits within eight weeks of treatment to identify patients with repeat presentations related to anemia or hemolysis. Results In our retrospective chart review, four of seventeen patients (25%) treated with artesunate had laboratory evidence of PADH. None of these patients were symptomatic and none required readmission or medical intervention. Haptoglobin levels remained low in most patients up to four weeks after treatment, regardless of the presence of PADH, and lactate dehydrogenase (LDH) levels slowly declined over this period. We identified 92 patients in the PHIS database who were treated with artesunate. Of these, three patients (3.3%) had a repeat presentation within four weeks with one or more diagnosis suggestive of new onset anemia. Repeat presentations occurred 5-13 days after initial admission for malaria. Conclusion PADH is common in US pediatric patients treated with artesunate for severe malaria. However, severe hemolysis requiring repeat emergency room visit or readmission is rare. We find that haptoglobin and LDH levels were not useful as initial screening labs for PADH in pediatric patients. Together, our findings call into question the utility of weekly laboratory monitoring, as opposed to symptom-based monitoring, to identify pediatric patients at risk of readmission for PADH. Additional studies are necessary to determine which patients would benefit from weekly laboratory monitoring and which can be monitored clinically.

Enriching Clinical Trials Enrolling Children With Cerebral Malaria Using Admission Demographics, Physical Examination and Point-of-care Testing Results.

Multiple clinical trials evaluating therapies for cerebral malaria (CM) have failed to demonstrate improved outcomes. This may derive from inclusion of children at all risk levels, including those at low risk of mortality or neurologic morbidity, limiting power to detect significant differences between intervention arms. One solution is enrichment, enrolling clinical trial participants at higher risk of adverse outcomes. We assessed if demographic, physical examination and point-of-care laboratory testing results in combination could identify children with CM at higher risk of death or neurologic disability. Retrospective case-control study of 1674 children hospitalized with CM in Blantyre, Malawi. We used univariate and multivariate analyses of admission factors to find the most parsimonious model associated with death or neurologic disability. To assess the clinical utility of the models, we evaluated derived probability density curve separation. Blantyre Coma Score (BCS), deep breathing and high blood lactate were independently associated with mortality. The derived receiver operating curve yielded an area under the curve of 0.7118. There was poor separation of derived probability density curves predicting death or survival, indicating limited clinical utility of this model. On multivariate modeling of neurologic sequelae in CM survivors, only BCS was associated with adverse outcomes (area-under-the-curve = 0.6151). Probability density curves again largely overlapped, demonstrating limited utility of BCS alone in outcome prediction. Combinations of admission demographic, clinical and point-of-care laboratory factors are inadequate to predict prognosis in children with CM. Higher technology assessment methods are necessary for clinical trial enrichment.

Safety and pharmacokinetic properties of a new formulation of parenteral artesunate in healthy Thai volunteers

BackgroundParenteral artesunate is the first-line therapy for severe malaria. Artesunate, in its current formulation, must be prepared immediately before administration by first dissolving in sodium bicarbonate solution and then diluting in saline. A novel solvent for rapid and stable single step reconstitution of artesunate was recently developed showing improved solubility and stability. This study aimed to compare the safety and pharmacokinetic properties of the currently available and newly developed parenteral formulation of artesunate in healthy Thai volunteers.MethodsThis was an open-label, randomized, 4 periods, 4-treatments, 24-sequence, single-dose, cross-over study in 72 male and female healthy Thai volunteers. Frequent pharmacokinetic samples were collected in all volunteers at each dose occasion. Observed concentration–time profiles were analysed with a non-compartmental approach followed by a bioequivalence evaluation.ResultsBoth intramuscular and intravenous administrations of the new parenteral formulation of artesunate were safe and well-tolerated, with no additional safety signals compared to the currently used formulation. The pharmacokinetic properties of artesunate and its active metabolite, dihydroartemisinin, were well-characterized, and showed rapid conversion of artesunate into dihydroartemisinin. Intramuscular administration of the newly formulated artesunate resulted in almost complete bioavailability of dihydroartemisinin. The pharmacokinetic properties were similar between the old and new formulation.ConclusionsThe new and more easily prepared formulation of artesunate was safe and well-tolerated, with similar pharmacokinetic properties compared to the currently used formulation. Dihydroartemisinin, the active metabolite responsible for the majority of the anti-malarial effect, showed equivalent exposure after both intravenous and intramuscular administration of artesunate, suggesting that both routes of administration should generate comparable therapeutic effects.Trial registration: The study was registered to clinicaltrials.gov (#TCTR20170907002).

Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy.

Background/Objectives: YAT2150 is a first-in-class antiplasmodial compound that has been recently proposed as a new interesting drug for malaria therapy. Methods/Results: The fluorescence of YAT2150 rapidly increases upon its entry into Plasmodium, a property that can be of use for the design of highly sensitive diagnostic approaches. YAT2150 blocks the in vitro development of the ookinete stage of Plasmodium and, when added to an infected blood meal, inhibits oocyst formation in the mosquito. Thus, the compound could possibly contribute to future transmission-blocking antimalarial strategies. Cell influx/efflux studies in Caco-2 cells suggest that YAT2150 is internalized by endocytosis and also through the OATP2B1 transporter, whereas its main export route would be via OSTα. YAT2150 has an overall favorable drug metabolism and pharmacokinetics profile, and its moderate cytotoxicity can be significantly reduced upon encapsulation in immunoliposomes, which leads to a dramatic increase in the drug selectivity index to values close to 1000. Although YAT2150 binds amyloid-forming peptides, its in vitro fluorescence emission is stronger upon association with peptides that form amorphous aggregates, suggesting that regions enriched in unstructured proteins are the preferential binding sites of the drug inside Plasmodium cells. The reduction of protein aggregation in the parasite after YAT2150 treatment, which has been suggested to be directly related to the drug's mode of action, is also observed following treatment with quinoline antimalarials like chloroquine and primaquine. Conclusions: Altogether, the data presented here indicate that YAT2150 can represent the spearhead of a new family of compounds for malaria diagnosis and therapy due to its presumed novel mode of action based on the interaction with functional protein aggregates in the pathogen.

Antiplasmodial activities of n-hexane and water fractions of Dennettia tripetala leaf extract in Wistar rats

Many people die from malaria, a global health crisis. Most global malaria cases and deaths occur in sub-Saharan Africa. The rising resistance of Plasmodium spp. to antimalarial medications is hindering efforts to eradicate the illness. This study tested Dennettia tripetala leaf extract, N-hexane, and water fractions for antimalarial activity in rats. We used standard methods to screen Dennettia tripetala solvent (N-hexane and water) for phytochemical components. We tested the antimalarial potential of rats using Peters' 4-day suppressive, Rane's curative, and prophylactic tests. After conducting an exhaustive investigation, it was discovered that both fractions contained varying amounts of flavonoids, alkaloids, terpenoids, and saponins. There was a significant amount of antimalarial activity demonstrated by both fractions across all test models (P<0.05). Compared to the water fraction, Dennettia tripetala's n-hexane fraction was highly chemosuppressive and curative. Dennettia tripetala n-hexane has chemoprophylactic, curative, and chemosuppressive effects. The curative effect was 62.3% to 72.4%, and the chemosuppressive effect was 51.2% to 88.5%. Chemoprophylactic activity was 32.1%–61.2%. At 250–1500 mg/kg, Combretum nigricans butanol suppressed 40.3%, 54.1%, and 69.1%, respectively. Therapeutic effects were 26.2%, 36.9%, and 34.5%, while chemoprophylaxis was 48.4%, 70.0%, and 87.4%. Both Dennettia tripetala solvent fractions have antimalarial activity, suggesting they may be effective in different malaria therapy stages.

LC-MS analysis of Urtica urens water extracts: active ingredients and their impact on beta-hematin formation

This study investigates the potential antimalarial efficacy of aqueous extracts from various parts of dwarf nettle (Urtica urens)-leaves, roots, and stems-by examining their ability to inhibit beta-hematin formation. The findings indicate that extracts from the roots and stems exhibit minimal antimalarial activity, while the leaf extracts show considerable promise. When the leaf extract was diluted, it maintained its antimalarial activity at concentrations up to 50%, but effectiveness decreased with further dilution. This decline may be attributed to the reduced concentrations of the active compounds present in the water extracts. The leaf extract was effective at concentrations ranging from 1 mg/ml to 0.5 mg/ml, but lost its activity at 0.3 mg/ml, likely due to inadequate levels of these compounds at this level. LC-MS analysis identified key flavonoids in the leaf extract, including flavanols such as Myricetin 3-O-rutinoside, Isorhamnetin 3-O-glucoside 7-O-rhamnoside, Kaempferol 3,7-diglucoside, Kaempferol-3-O-rutinoside, Rutin, Apigenin 7-O-diglucuronide, Kaempferol 3-O-(6''-acetyl-galactoside) 7-O-rhamnoside and flavanones such as Luteolin 7-O-diglucuronide. Examining their chemical structures offers insights into how these flavonoids might interact with heme, thereby enhancing our understanding of their antimalarial potential and supporting their consideration as candidates for malaria therapy.

Recent Advancement in Drug Development for Treating Malaria using Herbal Medicine and Nanotechnological Approach.

More than two hundred million people around the world are infected with malaria, a blood-borne disease that poses a significant risk to human life. Single medications, such as lumefantrine, primaquine, and chloroquine, as well as combinations of these medications with artemisinin or its derivatives, are currently being used as therapies. In addition, due to rising antimalarial drug resistance, other therapeutic options are needed immediately. Furthermore, due to anti-malarial medication failures, a new drug is required. Medication discovery and development are costly and time-consuming. Many malaria treatments have been developed however, most treatments have low water solubility and bioavailability. They may also cause drug-resistant parasites, which would increase malaria cases and fatalities. Nanotechnology may offer a safer, more effective malaria therapy and control option. Nanoparticles' high loading capacity, concentrated drug delivery, biocompatibility, and low toxicity make them an attractive alternative to traditional therapy. Nanotechnology-based anti-malarial chemotherapeutic medications outperform conventional therapies in therapeutic benefits, safety, and cost. This improves patient treatment compliance. The limitations of malaria treatments and the importance of nanotechnological approaches to the treatment of malaria were also topics that were covered in this review. The most recent advancements in nanomaterials and the advantages they offer in terms of medication delivery are discussed in this article. The prospective therapy for malaria is also discussed. Additionally, the limitations of malaria therapies and the importance of nanotechnology-based approaches to the treatment of malaria were explored.

Hybrid Diffusion Model for Stable, Affinity-Driven, Receptor-Aware Peptide Generation.

The convergence of biotechnology and artificial intelligence has the potential to transform drug development, especially in the field of therapeutic peptide design. Peptides are short chains of amino acids with diverse therapeutic applications that offer several advantages over small molecular drugs, such as targeted therapy and minimal side effects. However, limited oral bioavailability and enzymatic degradation have limited their effectiveness. With advances in deep learning techniques, innovative approaches to peptide design have become possible. In this work, we demonstrate HYDRA, a hybrid deep learning approach that leverages the distribution modeling capabilities of a diffusion model and combines it with a binding affinity maximization algorithm that can be used for de novo design of peptide binders for various target receptors. As an application, we have used our approach to design therapeutic peptides targeting proteins expressed by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) genes. The ability of HYDRA to generate peptides conditioned on the target receptor's binding sites makes it a promising approach for developing effective therapies for malaria and other diseases.

The characteristic structural and functional dynamics of P. falciparum DHFR binding with pyrimidine chemotypes implicate malaria therapy design

Dihydrofolate reductase (DHFR) enzyme regulates de-novo folate synthesis in Plasmodium falciparum, hence a critical malaria drug target. Pyrimethamine inhibits DHFR, but resistance and lack of cross-species activity are key challenges. Therefore, this study is set to investigate more potent nitrogenous heterocyclic compounds against DHFR. Docking and MD simulations were employed to gain insight into the compounds’ binding free energies and conformational stabilities, while cross-species activity was determined using sequence alignment. Among the 500 screened compounds, PMD_01 (−12.2 kcal/mol), PMD_02 (−11.1 kcal/mol), PMD_03 (−10.7 kcal/mol), and PMD_04 (−10.7 kcal/mol) have the highest binding affinities against pfDHFR compared to pyrimethamine (−7.9 kcal/mol). Critical amino acids for binding interactions in the active site of pfDHFR include Leu45, Thr107, Ile164, and Thr170. PMD-bound systems showed higher binding free energy than pyrimethamine, except PMD_03. Hydrogen bonding interactions with Gly159, Ser101, Ser104, Ser160, Ile157, and Lys48 played significant roles in the binding interaction of these compounds as opposed to Asp53 in pyrimethamine. The four systems converged around 1.90 Å RMSD and showed more stability than pyrimethamine-bound and unbound pfDHFR. The pocket's residues across the four plasmodia were highly conserved, but Phe116 and Ile164 replaced Met in P. knowlesi and Tyr in the other species. PMD_01, PMD_02, PMD_03, and PMD_04 showed promising inhibition against pfDHFR and are, thus, potential antimalarial agents against plasmodia DHFR homologues.

Entire expressed peripheral blood transcriptome in pediatric severe malarial anemia

This study on severe malarial anemia (SMA: Hb < 6.0 g/dL), a leading global cause of childhood morbidity and mortality, compares the entire expressed whole blood host transcriptome between Kenyan children (3-48 mos.) with non-SMA (Hb ≥ 6.0 g/dL, n = 39) and SMA (n = 18). Differential expression analyses reveal 1403 up-regulated and 279 down-regulated transcripts in SMA, signifying impairments in host inflammasome activation, cell death, and innate immune and cellular stress responses. Immune cell profiling shows decreased memory responses, antigen presentation, and immediate pathogen clearance, suggesting an immature/improperly regulated immune response in SMA. Module repertoire analysis of blood-specific gene signatures identifies up-regulation of erythroid genes, enhanced neutrophil activation, and impaired inflammatory responses in SMA. Enrichment analyses converge on disruptions in cellular homeostasis and regulatory pathways for the ubiquitin-proteasome system, autophagy, and heme metabolism. Pathway analyses highlight activation in response to hypoxic conditions [Hypoxia Inducible Factor (HIF)−1 target and Reactive Oxygen Species (ROS) signaling] as a central theme in SMA. These signaling pathways are also top-ranking in protein abundance measures and a Ugandan SMA cohort with available transcriptomic data. Targeted RNA-Seq validation shows strong concordance with our entire expressed transcriptome data. These findings identify key molecular themes in SMA pathogenesis, offering potential targets for new malaria therapies.

Development of Phytoconstituents from Spathodea campanulata Flowers as Potential Antimalarial Agents

Background: Considering the majority of pharmaceutical firms focus on using herbal remedies as an alternative source of essential components, herbal remedies are extremely significant to pharmacological researchers. Spathodea campanulata is one of the members of the Bignoniaceae family. It is popular for its curative properties Aim: This research aimed to assess the possibility of bioactive elements and antioxidant impacts of the methanol fraction of Spathodea campanulata flowers. Objectives: The objective of this research was to assess the achievable bioactive elements and antioxidant impacts of the methanol fraction of Spathodea campanulata flowers. Methods: GC-MS was adopted to identify the phytoconstituents present in the extract. In the present study, we utilized computational modelling with the Schrödinger Maestro 11.2 edition to make benefit of interactions among 42 bio-active components and anti-malarial targets (1LDG and 2ANL). Results: In the methanol extract of the Spathodea campanulata flowers, phytochemical research revealed the presence of terpenoids, glycosides, carbohydrates, steroids, and flavonoids. Forty-two phytoconstituents, notably methyl-beta-d-galactopyranoside, 4-hydroxybenzoic acid, and 1,2- ethanediol monobenzoate, were determined through GC-MS analysis. Docking analysis of 42 bioactive compounds demonstrated that 1,2-ethanediol mono benzoate, 4-hydroxy benzoic acid, and methyl.beta.-d-galactopyranoside had higher G-Scores with 1LDG and 2ANL. Conclusion: In this work, multiple phytoconstituents discovered in a methanol extract of the S. campanulata flower were determined. As a result of this research, four phytoconstituents from the flower extracts may be created as an exciting new therapy for malaria.

Therapeutic efficacy and tolerability of artemether–lumefantrine for uncomplicated Plasmodium falciparum malaria in Niger, 2020

BackgroundMonitoring therapeutic efficacy is important to ensure the efficacy of artemisinin-based combination therapy (ACT) for malaria. The current first-line treatment for uncomplicated malaria recommended by the National Malaria Control Program in Niger is artemether–lumefantrine (AL). In 2020, an in vivo study was carried out to evaluate clinical and parasitological responses to AL as well as the molecular resistance to the drug in three sentinel sites: Agadez, Tessaoua and Gaya, in Niger.MethodsA multi-center, single-arm trial was conducted according to the 28-day World Health Organization (WHO) 2009 therapeutic efficacy study protocol. Children between 6 months and 15 years with confirmed uncomplicated Plasmodium falciparum infection and 1000–200,000 asexual parasites/μL of blood were enrolled and followed up for 28 days. Uncorrected and PCR-corrected efficacy results at day 28 were calculated, and molecular correction was performed by genotyping the msp1, msp2, and glurp genes. The pfk13, pfdhfr, pfdhps, pfcrt and pfmdr genes were analyzed by PCR and Sanger sequencing. The Kaplan–Meier curve assessed parasite clearance.ResultsA total of 255 patients were enrolled in the study. The adequate clinical and parasitological response after PCR correction was 98.9% (95% CI 96.4–101.0%), 92.2% (85.0–98.5%) and 97.1% (93.1–101.0%) in Gaya, Tessaoua and Agadez, respectively. No adverse events were observed. Ten mutations (SNP) were found, including 7 synonyms (K248K, G690G, E691E, E612E, C469C, G496G, P718P) and 3 non-synonyms (N594K, R255K, V714S). Two mutations emerged: N594K and V714S. The R255K mutation detected in Southeast Asia was also detected. The pfdhpsK540E and pfdhfrI164L mutations associated with high levels of resistance are absent. There is a reversal of chloroquine resistance.ConclusionThe study findings indicate that AL is effective and well tolerated for the treatment of uncomplicated malaria in three sites in Niger. The emergence of a pfk13 mutation requires additional testing such as the Ring Stage Assay and CRISPR/Cas9 to confirm the role of these emerging mutations.Trial registration NCT05070520, October 7, 2021.

Artemisinin optimization based on malaria therapy: Algorithm and applications to medical image segmentation

This study proposes an efficient metaheuristic algorithm called the Artemisinin Optimization (AO) algorithm. This algorithm draws inspiration from the process of artemisinin medicine therapy for malaria, which involves the comprehensive eradication of malarial parasites within the human body. AO comprises three optimization stages: a comprehensive eliminations phase simulating global exploration, a local clearance phase for local exploitation, and a post-consolidation phase to enhance the algorithm's ability to escape local optima. In the experimental, this paper conducts a qualitative analysis experiment on the AO, explaining its characteristics in searching for the optimal solution. Subsequently, AO is then tested on the classical IEEE CEC 2014, and the latest IEEE CEC 2022 benchmark function sets to assess its adaptability. Comparative analyses are conducted against eight well-established algorithms and eight high-performance improved algorithms. Statistical analyses of convergence curves and qualitative metrics revealed AO's robust competitiveness. Lastly, the AO is incorporated into breast cancer pathology image segmentation applications. Using 15 authentic medical images at six threshold levels, AO's segmentation performance is compared against eight distinguished algorithms. Experimental results demonstrated AO's superiority in terms of image segmentation accuracy, Feature Similarity Index (FSIM), Peak Signal-to-Noise Ratio (PSNR), and Structural Similarity Index (SSIM) over the contrast algorithms. These results emphasize AO's efficiency and its potential in real-world optimization applications. The source codes22https://github.com/aliasgharheidaricom/Artemisinin-Optimizer-using-Malaria-Therapy-Algorithm-and-Applications-to-Medical-Image-Segmentation. of this paper are available in https://aliasgharheidari.com/AO.html and other public websites33https://ch.mathworks.com/matlabcentral/fileexchange/165791-artemisinin-optimization-ao-based-on-malaria-therapy..

Malaria Parasitemia and Severe Health Complications in Children Under Five Years of Age in Nigeria: A Study Using the Demographic and Health Survey (DHS) Malaria Indicator Survey (MIS) 2021.

In Nigeria, 97% of the population is at risk of contracting malaria. It is transmitted by female Anopheles mosquitoes carrying the Plasmodium parasite and can be lethal. An estimated 55 million illnesses and 80,000 deaths per year result from it. Children under five are more likely to contract malaria. Efforts to control malaria in Nigeria include indoor residual spraying, insecticide-treated bed nets, and quick detection and treatment of confirmed cases with effective antimalarial medications. These attempts have been impeded by limited healthcare access, poor financing, and drug-resistant parasites. Thus, the study of therelationship between malaria complications and housing for children under five is essential. The Demographic and Health Survey (DHS) Malaria Indicator Survey (MIS) 2021, a nationally representative data set from developing countries on population and health, was used for this study. A sample size of 13,727 was employed (n=13,727). Logistic regression analyses were conducted to test the association between the type of place of residence and malaria complications (outcome). Overall, 4.2% (n=570, weight HV005) of participants in the sample reported malaria complications. The results of the logistic regression revealed that children residing in urban settlements (aOR 0.37, 95% CI 0.37-0.37, p-value <0.001), children from the poorest class families (aOR 11.63, 95% CI 1.62-1.63, p-value 0.004), children from poorer class families (aOR 7.56, 95% CI 7.55-7.57, p-value <0.001), children from middle-class families (aOR 4.05, 95% CI 4.03-9.06, p-value <0.001), children from richer class families (aOR 1.22, 95% CI 2.21-2.23, p-value <0.001), children of mothers with primary education (aOR 0.42, 95% CI 2.32-4.112, p-value 0.001), children of mothers with secondary education (aOR 0.24, 95% CI 3.21-3.22, p-value <0.001), children of mothers with higher education (aOR 0.08, 95% CI 0.72-0.80, p-value <0.001), and children of the female gender (aOR 0.65, 95% CI 0.65-0.66, p-value <0.001) are all associated with severe malaria complications. In conclusion, the study examined malaria complications in Nigerian children under five by residency. The findings imply that rural children are more likely to have serious malaria complications than urban children. This emphasizes the necessity for targeted malaria therapies in rural areas with limited healthcare access.

Evaluation of the antiplasmodial activity of &lt;i&gt;Curcuma longa&lt;/i&gt; (turmeric - Zingiberaceae) on &lt;i&gt;Plasmodium berghei&lt;/i&gt; in laboratory mice.

Malaria is a leading cause of morbidity and mortality worldwide, especially in developing countries and in sub-Saharan Africa where most malaria cases and deaths occur. The resistance of malaria parasites to most anti-malaria drugs, coupled with the high cost and the toxic effects of some drugs has posed a challenge for the search of new effective anti-malarial compounds of low cost. The study aims to determine the antiplasmodial activity of Curcuma longa against Plasmodium berghei in rodents. A total of 110 Swiss albino mice weighing 18-30 grams were used for the study: 35 for the toxicity test and 75 for the antimalarial study. For each test, 25 mice were inoculated with drug-sensitive Nk65 Plasmodium berghei and divided into five groups of five animals each and each group was administered one of the following: 120mg/kg of ethanol extract, 120mg/kg water extract, 120mg/kg nHexane extracts of C. longa, 1.2mg/kg of pyrimethamine or 5mg/kg of Chloroquine (positive control) and 0.2mls of normal saline (negative control). The lethal dose concentration was above 1500mg/kg and the extracts showed significant (P&lt;0.05) antimalarial activity with the highest percentage inhibition (67.49%) recorded in the group treated with ethanol in the curative test, followed by the group given water in the suppressive test with (65.03%) and nHexane in the prophylactic test with percentage inhibition of 64.98%. There was a slight difference in the antimalarial activities of the extracts of different solvents which all had lower activities compared with the standard drugs (Chloroquine administered at 5mg/kg or pyrimethamine, 1.2mg/kg/day) but no total clearance of the parasite was recorded. C. longa possesses considerable antiplasmodial activity, which can be exploited in malaria therapy.

In vitro delayed response to dihydroartemisinin of malaria parasites infecting sickle cell erythocytes

BackgroundDecreased efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria has been previously reported in patients with sickle cell disease (SCD). The main purpose of this study was to investigate the in vitro susceptibility of isolates to dihydro-artemisinin (DHA) to provide a hypothesis to explain this treatment failure.MethodsIsolates were collected from patients attending health centres in Abidjan with uncomplicated P. falciparum malaria. The haemoglobin type has been identified and in vitro drug sensitivity tests were conducted with the ring stage assay and maturation inhibition assay.Results134 isolates were obtained. Parasitaemia and haemoglobin levels at inclusion were lower in patients with haemoglobin HbSS and HbSC than in patients with normal HbAA. After ex vivo RSA and drug inhibition assays, the lowest rate of parasitic growth was found with isolates from HbAS red cells. Conversely, a significantly higher survival rate of parasites ranging from 15 to 34% were observed in isolates from HbSS. Isolates with in vitro reduced DHA sensitivity correlate with lower RBC count and haematocrit and higher parasitaemia at inclusion compared to those with isolates with normal DHA sensitivity. However, this decrease of in vitro sensitivity to DHA was not associated with Kelch 13-Propeller gene polymorphism.ConclusionThis study highlights an in vitro decreased sensitivity to DHA, for isolates collected from HbSS patients, not related to the Pfkelch13 gene mutations. These results are in line with recent studies pointing out the role of the redox context in the efficacy of the drug. Indeed, SCD red cells harbour a highly different ionic and redox context in comparison with normal red cells. This study offers new insights into the understanding of artemisinin selective pressure on the malaria parasite in the context of haemoglobinopathies in Africa.

Critical Analysis of the Literature Comparing Artemisinin-Based Combination Therapy and Quinine Treatments for Uncomplicated Malaria in Pregnancy

Critical Analysis of the Literature Comparing Artemisinin-Based Combination Therapy and Quinine Treatments for Uncomplicated Malaria in Pregnancy

Placental Malaria and Its Relationship with Neonatal Birth Weight among Primigravidae: An Analytical Cross-sectional Study.

Malaria can be fatal during pregnancy, posing a serious risk to both mothers and fetuses, especially in sub-Saharan Africa. Primigravidae are particularly susceptible to placental malaria in areas with high rates of transmission due to insufficient immunity. This study aimed to determine the prevalence of placental malaria infection, risk factors, types of Plasmodium causing malaria during pregnancy, and its relationship with neonatal birth weight among primigravidae. This was an analytical cross-sectional study involving 357 primigravidae who delivered at Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, Nigeria. Placental blocks were taken from the pericentric area of the maternal surface of the placenta, and the birth weights of the neonates were recorded. The samples were fixed in 10% neutral-buffered formalin, and histopathological analysis was performed. The primary outcome measure was to determine the relationship between placental malaria and neonatal birth weight. Demographics and outcomes were analyzed using standard statistical tests. Multivariable regression models accounting for potential confounders were created for the primary and secondary outcomes with adjusted odds ratios as the measures of effect. The prevalence of placental malaria was 38.4%. Among the participants with positive placenta malaria parasitemia, 49.6%, 36.5%, and 13.9% had chronic, acute, and past placental malaria infections, respectively. Only Plasmodium falciparum was found in the placenta. According to the bivariate analysis, unbooked status (p = 0.001), non-use of intermittent preventive therapy for malaria (p < 0.001), and village dwelling (p = 0.020) were significantly associated with placental malaria. However, on multivariable logistic regression, only non-uptake of intermittent preventive therapy for malaria was independently associated with placental malaria (adjusted odds ratio, 2.2, 95% confidence interval: 1.20, 4.1, p = 0.011). There was a significant difference in the mean birth weight between those with placental malaria and those without placental malaria (2.8 ± 0.5 kg vs. 3.2 ± 0.4 kg, p = 0.001). Additionally, placental malaria was significantly associated with low birth weight among the primigravidae (p < 0.001). In Nigeria, there is a strong correlation between low birth weight and placental malaria in Primidravidae. Placental malaria was found to be independently correlated with non-uptake of intermittent preventive therapy for malaria.