Effective Malaria Treatment Research Articles

In-vivo Anti-Plasmodial Activity of Enantia chlorantha: A Potential Plasmodium berghei Survival Inhibitor

The emergence of resistance to existing antimalarial drugs has intensified the search for novel, effective, and affordable treatments for malaria. The sensitivity of strains of Plasmodium spp. to the commonly known antimalarial drugs over time undermines the effectiveness of treatment. Enantia chlorantha, traditionally used in African folk medicine, has shown potential antimalarial agents that inhibit parasite survival and growth. This study aimed to investigate the antimalarial efficacy of Enantia chlorantha extracts on Plasmodium berghei using in vivo approach. A total of 55 albino mice randomized into 5 groups were inoculated with an infection of 1.0 x 107 chloroquine sensitive strain of Plasmodium berghei intra-peritoneally. Methanol, n-hexane and ethyl acetate extracts of Enantia chlorantha stem-bark was extracted successfully using a Sohxlet extractor. Experimental mice were treated orally with doses of 5mg/kg, 10mg/kg, and 20mg/kg of each plant extract (EC2, EEA and EHEX treated groups), a dose of 10mg/kg chloroquine (standard control group), and a dose of 0.2ml Olive Oil (negative control group). The level of parasitaemia and death per day were used to assess the chemosuppressive effect and survival rate of the extracts. Data were analyzed using One Way Analysis of variance ANOVA followed by post hoc test, and were expressed as mean ± standard error of mean (M ± SEM), and percentage. All analyses were carried out at a 95% confidence interval, with a significance level set at P < 0.05. The treatment with various concentrations of Enantia chlorantha extracts (EC2, EEA, and EHEX) significantly reduced parasitaemia levels, with higher doses showing greater suppression. EC2 reduced parasitaemia from 1.00% (5 mg/kg) to 0.71% (20 mg/kg) with p=0.0003, while EEA reduced it from 1.15% (5 mg/kg) to 0.57% (20 mg/kg) with p=0.0028. EHEX showed a suppression from 1.09% (10 mg/kg) to 0.46% (20 mg/kg) with p=0.0001. Chemosuppression in EC2, EEA, and EHEX increased with dosage, with EEA at 20 mg/kg surpassing chloroquine in chemosuppression (85.64% vs. 69.86%, p=0.0009). In survival outcomes, EC2, EEA, and EHEX exhibited dose-dependent increases in survival index, with EEA at 20 mg/kg reaching 90%, but none matched chloroquine's 100% survival, Enantia chlorantha extracts particularly EEA significantly reduced parasitaemia level and increased chemosuppressive effect and survival index at high doses, indicating the potent antimalarial activity of Enantia chlorantha.

Effectiveness of Andrographis Paniculata Leaf Extract as an Antimalarial Through Plasmodium Heme Polymerization Inhibition

Malaria remains a significant and persistent public health challenge in Indonesia and other tropical regions. This disease is caused by the Plasmodium parasites, which are transmitted to humans through the bite of Anopheles mosquitoes and subsequently infect hepatocytes in the liver. Despite the long history of antimalarial drug development, resistance by Plasmodium species has led to diminishing effectiveness of conventional treatments such as chloroquine and artemisinin. Consequently, there is renewed interest in herbal remedies, such as Andrographis paniculata (sambiloto), which may offer alternative therapeutic options. To elucidate the pharmacological potential of Andrographis paniculata leaf extract as an antimalarial agent. This study involves a comprehensive literature review of scientific reports, including practical reports, case studies, systematic reviews, and meta-analyses, published within the past decade. The review was conducted through reputable scientific databases, including ScienceDirect, ResearchGate, and Google Scholar. The pharmacological efficacy of Andrographis paniculata leaf extracts is attributed to their high concentration of andrographolides, which have demonstrated the capability to inhibit heme polymerization in Plasmodium parasites. Both in vitro and in vivo studies have confirmed the safety and non-toxic nature of these extracts. Given the current state of genetic resistance in Plasmodium, the use of andrographolide extracts presents a promising avenue for effective malaria treatment. The concentrated andrographolide extract from Andrographis paniculata leaves exhibits significant antimalarial activity by targeting and inhibiting heme polymerization in Plasmodium. This suggests that it could serve as a viable alternative or complement to existing antimalarial therapies.

Health-Related Quality of Life due to malaria in the Brazilian Amazon using EQ-5D-3L.

Malaria is a mosquito-borne infectious disease caused by protozoa of the genus Plasmodium. Despite of the progress in malaria control in the last decades, malaria remains a major public health problem, contributing to increased morbidity and mortality in tropical and subtropical countries. Among American countries, Bolivia, Venezuela, and Brazil account for 73% of the cases. In Brazil, the majority of malaria cases is concentrated in Amazon region. This study estimated health-related quality of life (HRQoL) losses due to malaria in endemic areas of the Brazilian Amazon using the EQ-5D-3L instrument. We collected data from a convenience sample of 1,179 individuals aged 18 years or older. To measure the HRQoL loss, we matched individuals from the treatment group (with recent malaria) to those from the control group (without recent malaria) using Propensity Score Matching (PSM) and compared the difference in mean health utility between the groups. The results show a significant loss of HRQoL due to malaria. The mean utility was 0.69 and 0.83 for the treatment and control groups, respectively, representing a loss of quality of life of approximately 16.3% for individuals with recent malaria episodes. These findings underscore the importance of effective malaria prevention and treatment strategies, especially in areas where adverse socioeconomic conditions and a challenging epidemiological context exacerbate the impact of the disease. Continued investment in malaria control programs and improved access to health services are essential to mitigate the negative impact of this disease on the quality of life of affected populations.

A novel 4-aminoquinoline chemotype with multistage antimalarial activity and lack of cross-resistance with PfCRT and PfMDR1 mutants.

Artemisinin-based combination therapy (ACT) is the mainstay of effective treatment of Plasmodium falciparum malaria. However, the long-term utility of ACTs is imperiled by widespread partial artemisinin resistance in Southeast Asia and its recent emergence in parts of East Africa. This underscores the need to identify chemotypes with new modes of action (MoAs) to circumvent resistance to ACTs. In this study, we characterized the asexual blood stage antiplasmodial activity and resistance mechanisms of LDT-623, a 4-aminoquinoline (4-AQ). We also detected LDT-623 activity against multiple stages (liver schizonts, stage IV-V gametocytes, and ookinetes) of Plasmodium's life cycle, a feature unlike other 4-AQs such as chloroquine (CQ) and piperaquine (PPQ). Using heme fractionation profiling and drug uptake studies in PfCRT-containing proteoliposomes, we observed inhibition of hemozoin formation and PfCRT-mediated transport, which constitute characteristic features of 4-AQs' MoA. We also found minimal cross-resistance to LDT-623 in a panel of mutant pfcrt or pfmdr1 lines, but not the PfCRT F145I mutant that is highly resistant to PPQ resistance yet is very unfit. No P. falciparum parasites were recovered in an in vitro resistance selection study, suggesting a high barrier for resistance to emerge. Finally, a competitive growth assay comprising >50 barcoded parasite lines with mutated resistance mediators or major drug targets found no evidence of cross-resistance. Our findings support further exploration of this promising 4-AQ.

Intermittent Preventive Treatment of Malaria in Pregnancy and the Impact on Neonates in African Countries as Assessed by Entropy Weight and TOPSIS Methods.

Background/Objectives: In regions of Africa with a high prevalence of malaria, pregnant women in their first or second trimester should be administered intermittent preventive treatment in pregnancy (IPTp). However, infants may contract malaria despite the IPTp therapy that their mothers have received. The objective of the present investigation was to assess the symptoms and various treatments for neonatal malaria. Methods: Entropy weight and TOPSIS were used to achieve the study goal. The TOPSIS multi-attribute decision-making system was used to assess newborn malaria symptoms and select the optimal treatment, even for mothers receiving IPTp medication during pregnancy. The entropy weight approach calculated TOPSIS attribute weights. The present research used UNICEF data for 14 African nations in 2023. Results: The results indicated that neonates whose mothers received IPTp therapy ultimately contracted malaria, with diarrhea being the primary symptom. It is important to note that health providers administer a combination of zinc and oral rehydration solution (ORS) to infants as the most effective treatment for malaria symptoms, thereby abandoning the first-line treatment for malaria, artemisinin-based combination therapy (ACT). Conclusions: The most effective treatment for neonatal malaria is a combination of zinc and ORS, although less than half of children in Africa have access to ORS. Therefore, the findings of this study may encourage African countries to prioritize co-pack therapy in their procurement and supply, healthcare provider training, and expenditures. This therapy will also help alleviate the symptoms of malaria in neonates.

PHARE: a bioinformatics pipeline for compositional profiling of multiclonal Plasmodium falciparum infections from long-read Nanopore sequencing data.

The emergence of drug-resistant clones of Plasmodium falciparum is a major public health concern, and the ability to detect and track the spread of these clones is crucial for effective malaria control and treatment. However, in endemic settings, malaria infected people often carry multiple P. falciparum clones simultaneously making it likely to miss drug-resistant clones using traditional molecular typing methods. Our goal was to develop a bioinformatics pipeline for compositional profiling in multiclonal P. falciparum samples, sequenced using the Oxford Nanopore Technologies MinION platform. We developed the 'Finding P. falciparum haplotypes with resistance mutations in polyclonal infections' (PHARE) pipeline using existing bioinformatics tools and custom scripts written in python. PHARE was validated on three control datasets containing P. falciparum DNA of four laboratory strains at varying mixing ratios. Additionally, the pipeline was tested on clinical samples from children admitted to a paediatric hospital in the Central African Republic. The PHARE pipeline achieved high recall and accuracy rates in all control datasets. The pipeline can be used on any gene and was tested with amplicons of the P. falciparum drug resistance marker genes pfdhps, pfdhfr and pfK13. The PHARE pipeline helps to provide a more complete picture of drug resistance in the circulating P. falciparum population and can help to guide treatment recommendations. PHARE is freely available under the GNU Lesser General Public License v.3.0 on GitHub: https://github.com/Fippu/PHARE.

N-Substituted Phenylhydrazones Kill the Ring Stage of Plasmodium falciparum.

Antimalarial resistance has hampered the effective treatment of malaria, a parasitic disease caused by Plasmodium species. As part of our campaign on phenotypic screening of phenylhydrazones, a library of six phenylhydrazones was reconstructed and evaluated for their in vitro antimalarial and in silico receptor binding and pharmacokinetic properties. The structures of the phenylhydrazone hybrids were largely confirmed using nuclear magnetic resonance techniques. We identified two compounds which exhibited significant antimalarial potential against the ring stage (trophozoite) of 3D7 chloroquine-sensitive (CS) strain and DD2 chloroquine-resistant (CR) strains of Plasmodium falciparum with monosubstituted analogs bearing meta or para electron-donating groups showing significant activity in the single-digit micromolar range. Structure activity relationship is presented showing that electron-donating groups on the substituent hydrophobic pharmacophore are required for antimalarial activity. Compounds PHN6 and PHN3 were found to be the most potent with pIC50s (calculated form in vitro IC50s) of 5.37 and 5.18 against 3D7 CS and DD2 CR strains, respectively. Our selected ligands (PHN3 and PHN6) performed better when compared to chloroquine regarding binding affinity and molecular stability with the regulatory proteins of Plasmodium falciparum, hence predicted to be largely responsible for their in vitro activity. Pharmacokinetic prediction demonstrated that the phenylhydrazones may not cross the blood-brain barrier and are not P-glycoprotein (P-gp) substrates, a good absorption of 62% to 69%, and classified as a category IV compound based on toxicity grading.

Artesunate-Nanoliposome-TPP, a Novel Drug Delivery System That Targets the Mitochondria, Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Oxidative Stress and Inflammatory Effects.

Acute kidney injury (AKI) is a syndrome, posing a substantial healthcare burden. The pathological basis of AKI is associated with inflammation and oxidative stress which cause additional damage to mitochondria. Artesunate (ATS) is a derivative of artemisinin isolated from Artemisia annua L. that is an effective treatment for malaria and favored for the prevention and treatment of kidney diseases. However, there are still challenges related to its efficacy, including poor water solubility, limited oral bioavailability and short half-life. Liposome-based nanoparticles are used for drug delivery due to their ideal biocompatibility and their ability to improve the bioavailability of specific drugs and enhance drug efficacy. In this study, a novel TPP-based natural ATS-nanoliposome, namely T-A-Ls, was applied for the treatment of AKI. ATS was encapsulated with or without triphenylphosphonium (TPP)-modified nanoliposomes. AKI was induced by cisplatin in C57BL/6J mice and a cisplatin-induced injury model was generated in HK-2 cells in vitro. Blood urea nitrogen (BUN), serum creatinine (Scr) measurements and section staining were utilized to assess renal protective effect of T-A-Ls. Inflammatory-related factors and proteins were quantified via Elisa, Immunofluorescence and Western Blot (WB). The anti-mitochondrial oxidative stress effect of T-A-Ls was determined by ROS, JC-1 and oxygen consumption rate (OCR) kits. Immunohistochemistry and WB were conducted to measure associated protein expressions. In vivo biodistribution and the concentration of T-A-Ls in kidney were also explored. T-A-Ls exhibited good oxidative resistance, preferential renal uptake, mitochondrial targeting, and it ameliorated kidney injury in cisplatin-induced AKI mice. Mitochondrial dysfunction, ATP production and respiratory capacity were improved in damaged HK-2 cells; ROS content decreased while mitochondrial membrane potential recovered. T-A-Ls exerted renal protection by inhibiting inflammation and reducing oxidative stress; these effects were mediated by a downregulation in the expression of RAGE and iNOS and an upregulation in both Nrf2 and HO-1. T-A-Ls could improve the delivery of ATS to the kidney, offering a promising avenue to treat AKI.

Metabolic engineering of microbial and plant chasses to optimize artemisinin production

Abstract Artemisinin, a sesquiterpene lactone extracted from the sweet wormwood plant ( Artemisia annua ), is a crucial component in the production of artemisinin-based combination therapies (ACTs), the most effective treatment for malaria. In recent years, metabolic engineering has emerged as a powerful tool to enhance the production of artemisinin, both in microbial and plant chasses. This review article provides an overview of the recent literature on the metabolic engineering strategies employed to optimize artemisinin production, highlighting breakthroughs, challenges, and future directions.

Global trends in the burden of malaria: Contemporary diagnostic approaches, and treatment strategies

Malaria continues to pose a significant global health challenge, with 247 million cases reported in 2021, primarily concentrated in African countries. Despite substantial progress in reducing malaria cases and deaths over the past two decades, the COVID-19 pandemic disrupted healthcare systems, resulting in a temporary increase in cases and deaths in 2020. Nevertheless, between 2000 and 2021, an estimated 2 billion malaria cases and 11.7 million deaths were averted, with the majority occurring in the WHO African Region. Accurate diagnosis remains pivotal for effective malaria treatment, and various diagnostic methods have been employed, each with its own limitations. The effectiveness of these methods varies across different populations and environments. To combat the resurgence of malaria and the limitations of current interventions, there is a growing need for new technologies and integrated diagnosis and treatment. This paper reviews global trends in the burden of malaria; contemporary diagnostic approaches, and treatment strategies.

Modeling of malaria vaccine effectiveness on disease burden and drug resistance in 42 African countries

BackgroundThe emergence of antimalarial drug resistance poses a major threat to effective malaria treatment and control. This study aims to inform policymakers and vaccine developers on the potential of an effective malaria vaccine in reducing drug-resistant infections.MethodsA compartmental model estimating cases, drug-resistant cases, and deaths averted from 2021 to 2030 with a vaccine against Plasmodium falciparum infection administered yearly to 1-year-olds in 42 African countries. Three vaccine efficacy (VE) scenarios and one scenario of rapidly increasing drug resistance are modeled.ResultsWhen VE is constant at 40% for 4 years and then drops to 0%, 235.7 (Uncertainty Interval [UI] 187.8–305.9) cases per 1000 children, 0.6 (UI 0.4–1.0) resistant cases per 1000, and 0.6 (UI 0.5–0.9) deaths per 1000 are averted. When VE begins at 80% and drops 20 percentage points each year, 313.9 (UI 249.8–406.6) cases per 1000, 0.9 (UI 0.6–1.3) resistant cases per 1000, and 0.9 (UI 0.6–1.2) deaths per 1000 are averted. When VE remains 40% for 10 years, 384.7 (UI 311.7–496.5) cases per 1000, 1.0 (0.7–1.6) resistant cases per 1000, and 1.1 (UI 0.8–1.5) deaths per 1000 are averted. Assuming an effective vaccine and an increase in current levels of drug resistance to 80% by 2030, 10.4 (UI 7.3–15.8) resistant cases per 1000 children are averted.ConclusionsWidespread deployment of a malaria vaccine could substantially reduce health burden in Africa. Maintaining VE longer may be more impactful than a higher initial VE that falls rapidly.

Transcriptomics-Guided In Silico Drug Repurposing: Identifying New Candidates with Dual-Stage Antiplasmodial Activity.

In tropical and subtropical areas, malaria stands as a profound public health challenge, causing an estimated 247 million cases worldwide annually. Given the absence of a viable vaccine, the timely and effective treatment of malaria remains a critical priority. However, the growing resistance of parasites to currently utilized drugs underscores the critical need for the identification of new antimalarial therapies. Here, we aimed to identify potential new drug candidates against Plasmodium falciparum, the main causative agent of malaria, by analyzing the transcriptomes of different life stages of the parasite and identifying highly expressed genes. We searched for genes that were expressed in all stages of the parasite's life cycle, including the asexual blood stage, gametocyte stage, liver stage, and sexual stages in the insect vector, using transcriptomics data from publicly available databases. From this analysis, we found 674 overlapping genes, including 409 essential ones. By searching through drug target databases, we discovered 70 potential drug targets and 75 associated bioactive compounds. We sought to expand this analysis to similar compounds to known drugs. So, we found a list of 1557 similar compounds, which we predicted as actives and inactives using previously developed machine learning models against five life stages of Plasmodium spp. From this analysis, two compounds were selected, and the reactions were experimentally evaluated. The compounds HSP-990 and silvestrol aglycone showed potent inhibitory activity at nanomolar concentrations against the P. falciparum 3D7 strain asexual blood stage. Moreover, silvestrol aglycone exhibited low cytotoxicity in mammalian cells, transmission-blocking potential, and inhibitory activity comparable to those of established antimalarials. These findings warrant further investigation of silvestrol aglycone as a potential dual-acting antimalarial and transmission-blocking candidate for malaria control.

Effects of uncomplicated malaria parasitaemia on selected haematological parameters and phagocytes of children living in Port Harcourt, Southern Nigeria

This cross-sectional and case control study evaluated the effects of malaria parasites on selected haematological parameters of children living in Port Harcourt, Nigeria. A total of 352 participants were randomly recruited and their blood samples collected. Malaria diagnosis and estimation of haematological parameters were determined using standard parasitological and haematological methods respectively. Sociodemographics of participants showed that 109 (31%) of female children and 106 (30%) of male children were infected with malaria parasites. Overall prevalence of Plasmodium falciparum found was 215(61%). The study found a statistically significant difference in the mean values of packed cell volume (PCV), haemoglobin concentration (Hb), and white blood cell count (WBC) of Plasmodium parasitized children compared with their matched controls: PCV(34.83±2.76% versus 36.06±1.41%; P=0.001); Hb(11.58±0.92g/dL versus 11.98±0.46g/dL; P=0.001); WBC (8.96±4.56(x109/L) versus 7.33±1.39(x109/L); P=0.001).While the mean values of lymphocyte counts were relatively reduced in malaria infected children than their control participants (41.66±13.57(x109/L) versus 42.95±8.36(x109/L); P=0.27). A weak relationship was found to exist between density of parasitaemia and ages of children infected with malaria parasites (R2=0.0093; P=0.1584). Though more children had low parasitaemia (1-999 parasites/μL), followed with high parasitaemia (>10,000 parasites/μL), while few had moderate parasitaemia (1000-9999 parasites/μL). There was no case of complication with respect to WHO standard which described complicated or severe anaemia in malaria as haemoglobin (Hb) of < 5g/dl or packed cell volume (PCV) of < 15% with parasitemia of > 250,000 parasites/μL. Malaria parasites affect outcomes of some haematological parameters. We recommend that all febrile children in our study area should be tested for malaria parasites in conjunction with estimation of their full blood count for effective malaria diagnosis and treatment particularly in sub patent cases.

Adherence to 14-day radical cure for Plasmodium vivax malaria in Papua, Indonesia: a mixed-methods study

BackgroundReducing the risk of recurrent Plasmodium vivax malaria is critical for malaria control and elimination. Primaquine (PQ) is the only widely available drug against P. vivax dormant liver stages, but is recommended as a 14-day regimen, which can undermine adherence to a complete course of treatment.MethodsThis is a mixed-methods study to assess socio-cultural factors influencing adherence to a 14-day PQ regimen in a 3-arm, treatment effectiveness trial in Papua, Indonesia. The qualitative strand, consisting of interviews and participant observation was triangulated with a quantitative strand in which trial participants were surveyed using a questionnaire.ResultsTrial participants differentiated between two types of malaria: tersiana and tropika, equivalent to P. vivax and Plasmodium falciparum infection, respectively. The perceived severity of both types was similar with 44.0% (267/607) perceiving tersiana vs. 45.1% (274/607) perceiving tropika as more severe. There was no perceived differentiation whether malaria episodes were due to a new infection or relapse; and 71.3% (433/607) acknowledged the possibility of recurrence. Participants were familiar with malaria symptoms and delaying health facility visit by 1–2 days was perceived to increase the likelihood of a positive test. Prior to health facility visits, symptoms were treated with leftover drugs kept at home (40.4%; 245/607) or bought over the counter (17.0%; 103/607). Malaria was considered to be cured with ‘blue drugs’ (referring to dihydroartemisinin-piperaquine). Conversely, ‘brown drugs,’ referring to PQ, were not considered malaria medication and instead were perceived as supplements. Adherence to malaria treatment was 71.2% (131/184), in the supervised arm, 56.9% (91/160) in the unsupervised arm and 62.4% (164/263) in the control arm; p = 0.019. Adherence was 47.5% (47/99) among highland Papuans, 51.7% (76/147) among lowland Papuans, and 72.9% (263/361) among non-Papuans; p < 0.001.ConclusionAdherence to malaria treatment was a socio-culturally embedded process during which patients (re-)evaluated the characteristics of the medicines in relation to the course of the illness, their past experiences with illness, and the perceived benefits of the treatment. Structural barriers that hinder the process of patient adherence are crucial to consider in the development and rollout of effective malaria treatment policies.

Plasmodium falciparum kelch13 polymorphisms identified after treatment failure with artemisinin-based combination therapy in Niger

BackgroundArtemisinin-based combination therapy (ACT) is the most effective treatment for malaria, and has significantly reduced morbimortality. Polymorphisms associated with the Plasmodium falciparum Kelch gene (Pfkelch13) have been associated with delayed parasite clearance even with ACT treatment.MethodsThe Pfkelch13 gene was sequenced from P. falciparum infected patients (n = 159) with uncomplicated malaria in Niger. An adequate clinical and parasitological response (ACPR) was reported in 155 patients. Four (n = 4) patients had treatment failure (TF) that were not reinfections—two of which had late parasitological failures (LPF) and two had late clinical failures (LCF).ResultsThirteen single nucleotide polymorphisms (SNPs) were identified of which seven were non-synonymous (C469R, T508S, R515T, A578S, I465V, I437V, F506L,), and three were synonymous (P443P, P715P, L514L). Three SNP (C469R, F506L, P715P) were present before ACT treatment, while seven mutations (C469R, T508S, R515T, L514L, P443P, I437V, I465V) were selected by artemether/lumefantrine (AL)—five of which were non-synonymous (C469R, T508S, R515T, I437V, I465V). Artesunate/amodiaquine (ASAQ) has selected any mutation. One sample presented three cumulatively non-synonymous SNPs—C469R, T508S, R515T.ConclusionsThis study demonstrates intra-host selection of Pfkelch13 gene by AL. The study highlights the importance of LCF and LPF parasites in the selection of resistance to ACT. Further studies using gene editing are required to confirm the potential implication of resistance to ACT with the most common R515T and T508S mutations. It would also be important to elucidate the role of cumulative mutations.

Determinants of health seeking behaviours for malaria treatment in Cameroon

Background: Household health-seeking behaviour for malaria treatment is an important policy concern in malaria-endemic African countries. This paper aims to shed light on the determinants of household’s health-seeking behaviour for malaria treatment in Cameroon.Methods: The cross-sectional study used secondary data from the fourth Cameroonian household consumption survey conducted by the National Institute of Statistics. A stratified, 2-stage sampling was implemented with a sample of 918 households which sought malaria treatment from different alternatives providers. The multinomial probit model was used to estimate the probability based on socio-demographic and economics determinants for a household to choose between different types of providers of malaria treatment.Results: The findings of this study indicate that, the alternative providers for malaria treatment were: public health facilities (61.1%), private health facilities (8.5%), traditional healers (1.4%), pharmacies (4.6%), informal vendor (18%), other types of recourse (6.4%). The decision to choose the provider for malaria treatment depends on factors such as household head, region, level of education, religion, area of residence, socio-professional category, and gender. The level of education appears to be an important determinant of a household’s seeking behaviour. Those with higher education are more likely to seek care at formal health facilities.Conclusions: Health policy-makers need to strive to improve the socio-demographic and economic conditions and sensitize households on the appropriate alternative ways to ensure the universal access to diagnosis and effective treatment of malaria in line with the global strategies recommended by WHO to achieve malaria elimination by 2030.

P fmdr 1 and kelch 13 genes distribution among children that are 5years and below in Akure, Nigeria.

Malaria parasite resistant to drugs has been a major barrier to effective treatment of malaria. Therefore, the study aimed to evaluate the distribution of Plasmodium falciparum resistant Kelch protein gene on chromosome 13 (Kelch 13) and multidrug resistant (Pfmdr1) mutant genes among children aged five years and below who attended Mother and Child Hospital, Akure, Nigeria. Thin and thick smears were prepared from the blood collected aseptically through venepuncture from five hundred (500) children. Structured questionnaires were used to obtain demographic data from the respondents. Two hundred malaria positive samples were randomly selected from the 500 samples for PCR analysis to detect Pfmdr1 and Kelch 13 mutant genes. The results showed that of the 500 respondents, 288 (57.6%) were males while 21 (42.4%) were females. Pfmdr1distribution include: mixed group (mutant/wild) 38.5%, mutant gene 35.5%, wild gene 20.5% and the resistant genes were absent in 5.5% of the infected children. The mixed group of Pfmdr1 gene was higher among infants (51.9%), children with birth order 4 (60.0%) and children that have blood group B (51.3%), however, there is no significant difference in the distribution of Pfmdr1 between gender (χ2 = 0.634, df = 1, p > 0.05). There was a point mutation in the codon position 557 where the amino acid Alanine was replaced by Serine in the PfK13. The presence of Pfmdr1 mutant genes and point mutation in the PfK13 gene of P. falciparum among children, calls for development of innovative drugs targeted on these resistant strains.

Evaluation of anti-malarial activity and GC–MS finger printing of cannabis: An in-vivo and in silico approach

The development of an effective and affordable malaria treatment drug is required to reduce the number of deaths caused by this disease around the world. The in-vivo anti-malarial activities of Cannabis were investigated, as well as the in-silico antimalarial prediction of cannabis GC–MS compounds. Thirty albino mice were divided into six groups of five animals each at random: A, B, C, D, E and F. The animals in all the groups except the normal control group were infected with Plasmodium berghei NK-65 before the commencement of treatment. Each group was treated differently: A is a positive control; B, mice were administered 0.2 ml 2% DMSO with no infection; C, 10 mg/kg BW of chloroquine was administered; Animals in D, E, and F were given 100, 200, and 400 mg/kg BW of ethanolic cannabis leaf extract, respectively. Blood was drawn from the mice's tail, fixed on a slide, and examined under a microscope to determine the parasitaemia level of the infected mice at various intervals during treatment. The animals were sacrificed and blood collected for hematological studies. There was a significant decrease in percentage parasitemia and an increase in percentage inhibition in the treated group compared to infected group. The red blood cell (RBC), platelet, haematocrit (HCT) and percentage weight gain showed a significant increase (P ≤ 0.05) in the treatment groups compared to the infected mice. Tetrahydrocannabivarin showed high binding energy to α/β tubulin protein of Plasmodium falciparum compared to vinblastine. The decrease in parasitaemia percentage could be attributed to tetrahydrocannabivarin's inhibitory action on microtubules, which eventually leads to the cessation of parasite proliferation in RBC.

&lt;i&gt;In vivo&lt;/i&gt; antiplasmodial properties of fractions and flavonoids of &lt;i&gt;Pseudarthria hooheri&lt;/i&gt; Wight &amp; Arn. (Fabaceae)

Malaria is regarded as one of the most lethal diseases. Resistance to artemisinin and its derivatives jeopardises effective malaria treatment. Finding novel antimalarial chemicals is critical given the existing treatment situation. This work aimed to examine the antiplasmodial capabilities of &lt;i&gt;Pseudarthria hookeri&lt;/i&gt; fractions and flavonoids in vivo. The fractions and compounds antiplasmodial activity were evaluated on male Swiss albino mice infected with &lt;i&gt;Plasmodium berghei&lt;/i&gt;, and on healthy female Swiss albino mice, the crude extract's acute toxicity was assessed. The EtOAc fraction had significant antiplasmodial activity (32.53 percent suppression at 500 mg/kg BW) and considerably prolonged the survival period of infected mice (9.8 days) compared to control mice (7.8 days). Parasitaemia was dramatically reduced (85.01, 59.41, and 70.39 percent), and the mean survival time extended (11.33, 10.00, and 9.33 days) with 15, 20 and 35 mg/kg of quercetin (&lt;b&gt;1&lt;/b&gt;), 7-O-benzyl-6-prenylpinocembrin (&lt;b&gt;6&lt;/b&gt;) and 6,8-diprenyleriodictyol (&lt;b&gt;11&lt;/b&gt;) (isolates of the EtOAc fraction), respectively. BW loss and PCV reduction were also averted. Moreover, at 2500 mg/kg, the crude extract of &lt;i&gt;P. hookeri&lt;/i&gt; showed no acute toxicity in mice. LC-MS analysis of the EtOAc fraction enabled the identification of nine flavonoids, with &lt;b&gt;8&lt;/b&gt; and &lt;b&gt;11&lt;/b&gt; being the main components. The present investigation confirmed &lt;i&gt;P. hookeri&lt;/i&gt;'s antiplasmodial action, substantiating its ethnomedicinal application for malaria treatment.

Surveillance of Plasmodium malariae infection among inhabitants of rural areas in Ouidah-Kpomasse-Tori Bossito health district, Benin.

Among the Plasmodium species that infect humans, P. falciparum has been largely studied in malaria endemic areas. However, P. malariae infection is less documented among the human population. This study aimed to monitor the prevalence and distribution of P. malariae in Southern Benin. A cross-sectional survey was conducted in rural localities in the Ouidah-Kpomasse-Tori Bossito (OKT) health district in Southern Benin from June to October 2019. Socio-demographic data were collected using a questionnaire, while malaria infection data were obtained on the one hand by microscopy diagnosis and, on the other, by nested polymerase chain reaction (PCR). Based on microscopy, the prevalence of P. malariae mono-infection and coinfection of P. falciparum, P. malariae was respectively 2.3% and 1.2% in the OKT health district. This prevalence was higher (P < 0.01) than that reported by Damien et al. (2010) 10 years ago in the same study area with 0.7% and 0.3% of P. malariae and P. falciparum/P. malariae, respectively. Based on PCR analysis, P. malariae prevalence was 14.1%, including 5.2% of mono-infection and 8.9% of mixed infection with P. falciparum. Sub-microscopic Plasmodium infections were high (30.6%) and more pronounced in older participants (>20 years). The present study revealed that P. malariae increased in the OKT health district with a high prevalence of submicroscopic infection. Since our results provide valuable evidence of increasing P. malariae infection, the National Malaria Control Programs (NMCPs) must consider P. malariae when designing future measures for effective control and malaria treatment.