Treatment Of Malaria Research Articles

Antimalarial Mechanisms and Resistance Status of Artemisinin and Its Derivatives.

Artemisinin is an endoperoxide sesquiterpene lactone isolated from Artemisia annua and is often used to treat malaria. Artemisinin's peroxide bridge is the key structure behind its antimalarial action. Scientists have created dihydroartemisinin, artemether, artesunate, and other derivatives preserving artemisinin's peroxide bridge to increase its clinical utility value. Artemisinin compounds exhibit excellent efficacy, quick action, and minimal toxicity in malaria treatment and have greatly contributed to malaria control. With the wide and unreasonable application of artemisinin-based medicines, malaria parasites have developed artemisinin resistance, making malaria prevention and control increasingly challenging. Artemisinin-resistant Plasmodium strains have been found in many countries and regions. The mechanisms of antimalarials and artemisinin resistance are not well understood, making malaria prevention and control a serious challenge. Understanding the antimalarial and resistance mechanisms of artemisinin drugs helps develop novel antimalarials and guides the rational application of antimalarials to avoid the spread of resistance, which is conducive to malaria control and elimination efforts. This review will discuss the antimalarial mechanisms and resistance status of artemisinin and its derivatives, which will provide a reference for avoiding drug resistance and the research and development of new antimalarial drugs.

Bioassay-Guided Fractionation of Anti-Leishmania Amazonensis Extracts from Ampelozizyphus Amazonicus by High-Speed Countercurrent Chromatography.

Ampelozizyphus amazonicus Ducke, known as "saracura-mirá" in the Amazon rainforest, is valued for its traditional use in malaria prevention and treatment. The plant's roots and bark are employed for these purposes, while the wood is often overlooked. Given the global importance of leishmaniasis, this research focused on A. amazonicus anti-Leishmania amazonensis potential. The ethyl acetate extract from the bark (EAEB) exhibited the most effective inhibition of intracellular amastigote growth with IC50 7.0 μg mL-1 but showed high toxicity (CC50 9.0 μg mL-1). The wood ethanol (EW) and ethyl acetate (EAEW) extracts demonstrated promising results against L. amazonensis with IC50 15.8 μg mL-1 and 10.0 μg mL-1, CC50 50.5 μg mL-1 and 22.7 μg mL-1, respectively, with EW showing the greatest promise. High-speed countercurrent chromatography (HSCCC) combined with mass spectrometry (MS) off-line detection was employed for the bioassay-guided fractionation of EAEB and EAEW using HEMWat as a solvent system. These extracts showed to be rich in saponins and triterpenes, besides the presence of glycosylated flavonoids recently reported as minor compounds. The fractions obtained from HSCCC showed high toxicity. However, this technique proved effective in obtaining fractions with a high purity level, leading to the identification of a di-glycosylated triterpene saponin from EAEB, and melaleucic acid from EAEW. These findings highlight A. amazonicus as a potential source for developing new therapeutic alternatives for leishmaniasis and HSCCC as a technique enabling better separation efficiency of complex saponin matrices.

Therapeutic efficacy of artemether–lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Arba Minch Zuria District, Gamo Zone, Southwest Ethiopia

BackgroundArtemether–lumefantrine (AL) has been the primary anti-malarial drug used to treat uncomplicated Plasmodium falciparum malaria in Ethiopia since 2004. However, there have been recent reports of AL resistance mutations in different African countries, including Ethiopia. This is concerning and requires periodic monitoring of anti-malarial drug resistance. Therefore, the current study aimed to evaluate the therapeutic efficacy of AL in treating uncomplicated P. falciparum malaria in the Arba Minch Zuria District, Gamo Zone, Southwest Ethiopia.MethodsA single-arm prospective study with a 28-day follow-up period was conducted from July to October 2022. Capillary blood samples were collected for RDT and microscopic examination. The study enrolled monoinfected P. falciparum patients aged ≥ 18 years at Ganta Sira Health Post. Sociodemographic and clinical data were recorded, and a dried blood spot (DBS) was prepared for each participant. Nested polymerase chain reaction (nPCR) genotyping of the msp-1 and msp-2 genes was only performed for recurrent cases to distinguish between recurrence and reinfection. Data entry and analysis were performed using the WHO Excel spreadsheet and SPSS version 26.ResultsA total of 89 patients were enrolled, and 67 adequately completed the 28-day follow-up period. AL showed a 100% clearance rate for fever on day 2 and asexual parasites on day 3. Gametocytes were detected in 13.5% (12/89) of the participants. The gametocyte clearance rate was 58.3% (7/12) until day 7 and 100% (12/12) until day 14. Five participants developed recurrent malaria, three of whom experienced relapse and two of whom experienced reinfection. Based on the Kaplan–Meier survival analysis, the PCR-uncorrected and PCR-corrected cumulative incidence of success were 93.7% (95% CI 85.5–97.3) and 96.2% (95% CI 85.5–98.7), respectively.ConclusionAL was efficacious in treating uncomplicated P. falciparum malaria in the study area. However, the detection of recurrent patients highlights the need for continuous efficacy studies in this area.

Nanotechnology in Malaria Treatment: Targeted Drug Delivery Systems and Future Applications

Malaria continued to be a major global health challenge, particularly in regions with high disease burden, despite advancements in treatment options such as Artemisinin-based Combination Therapies (ACTs). The emergence of nanotechnology offered a transformative approach to malaria treatment, with its potential to improve drug delivery, bioavailability, and therapeutic outcomes. This review examined the current applications and advancements in nanotechnology for malaria treatment, focusing on the use of nanocarriers like liposomes, polymeric nanoparticles, and solid lipid nanoparticles. These systems enhanced the efficacy of antimalarial drugs by enabling targeted delivery to malaria-infected cells, overcoming drug resistance, and offering controlled release mechanisms. The review also explored emerging strategies such as combination therapies, personalized nanomedicine, responsive nanoparticles, and vaccine delivery systems. While nanotechnology holds great promise, challenges including safety, scalability, regulatory hurdles, and cost were addressed. Future directions suggest innovations such as smart nanocarriers, personalized treatments, and enhanced diagnostic integration. Methodologically, this review synthesized data from recent preclinical and clinical research to provide a comprehensive analysis of nanotechnology’s role in advancing malaria treatment. Global collaboration and interdisciplinary research will be pivotal in realizing the full potential of nanotechnology in combating malaria. Keywords: Nanotechnology, malaria treatment, drug delivery systems, liposomes, nanoparticles, targeted therapy, drug resistance

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.

Advances in Artemisinin Resistance: Mechanisms, Detection, and Novel Therapeutic Approaches

Artemisinin-based combination therapies (ACTs) have been instrumental in reducing global malaria mortality over the past two decades. However, the rise of artemisinin resistance, particularly in Southeast Asia and parts of Africa, threatened these gains. Artemisinin resistance was characterized by delayed parasite clearance and is primarily driven by mutations in the kelch13 (K13) gene, which reduce the drug’s efficacy. This review explored the mechanisms behind artemisinin resistance, including genetic mutations, parasite stress responses, and reduced ring-stage sensitivity. Detection strategies, such as the use of molecular markers like K13 mutations and in vitro phenotypic assays, were discussed in detail. To combat resistance, novel therapeutic approaches were emerging, including the optimization of ACTs, the use of triple-drug regimens, host-directed therapies, and gene-editing technologies. The article highlighted the need for new antimalarial drugs, improved diagnostic tools, and global collaboration to address this growing challenge. We conducted the review by analyzing recent literature and summarizing advances in both resistance mechanisms and therapeutic strategies. Finally, future directions were outlined, emphasizing the importance of research, regulatory frameworks, and investment to mitigate the spread of resistance and ensure effective malaria control. Keywords: Artemisinin resistance, K13 mutations, malaria treatment, combination therapies, gene editing, host-directed therapies.

Incidence of malaria infection and adherence to antimalarial treatment guidelines at Bingham University Teaching Hospital, Jos, Nigeria

The development of antimalarial resistance has been a foremost barrier to malaria control. The aim of this study was to investigate the incidence of malaria infection and adherence to Antimalarial Treatment Guidelines (ATG) at Bingham University Teaching Hospital (BhUTH), Jos, Nigeria. A descriptive cross-sectional study was carried out to assess malaria infection diagnosis, antimalarials prescription pattern and adherence to the ATG by physicians over a two-year period. The study extracted data from 570 prescriptions of different patients and 227 patient files. The demographics of the patients was also obtained. Analyses were carried out using Statistical Package for the Social Sciences (SPSS). The study revealed that of the 227 patients treated for malaria, 65 % (n=148) underwent laboratory investigations before treatment while 35 % (n=79) were treated empirically. Artemether-Lumefantrine was the most prescribed antimalarial for treatment of uncomplicated malaria while parenteral Arteether andSulfadoxine/Pyrimethamine (SP) was the mainstay for treating severe malaria. This study also revealed that physicians placed patients on antimalarials without confirmatory test indicating poor adherence to the ATG. Adherence to ATG has the potential to limit resistance to antimalarial drugs and should therefore be discouraged.

Socioeconomic and Environmental Risk Factors for Malaria in Young Children: A Review

Malaria remained a significant public health challenge in sub-Saharan Africa, disproportionately affecting children under five years of age. Understanding the socioeconomic and environmental risk factors associated with malaria in this vulnerable population was crucial for developing targeted interventions to reduce transmission and improve health outcomes. This review examined the complex interplay between socioeconomic status, housing conditions, environmental factors, and malaria risk among young children. A comprehensive literature search was conducted to synthesize current research findings on the topic. Key socioeconomic determinants included household income, maternal education, and access to preventive measures. Children from low-income families were at higher risk due to limited resources for malaria prevention and treatment, as well as poorer living conditions that facilitate mosquito breeding. Environmental factors such as proximity to stagnant water bodies, inadequate sanitation, and climate variability further exacerbated malaria transmission. The review highlighted the need for multifaceted approaches that address both biological and social determinants of health to effectively reduce the burden of malaria among children under five in sub-Saharan Africa. Keywords: Malaria, Socioeconomic factors, Environmental factors, young children, Sub-Saharan Africa

AnophelesModel: An R package to interface mosquito bionomics, human exposure and intervention effects with models of malaria intervention impact.

In recent decades, field and semi-field studies of malaria transmission have gathered geographic-specific information about mosquito ecology, behaviour and their sensitivity to interventions. Mathematical models of malaria transmission can incorporate such data to infer the likely impact of vector control interventions and hence guide malaria control strategies in various geographies. To facilitate this process and make model predictions of intervention impact available for different geographical regions, we developed AnophelesModel. AnophelesModel is an online, open-access R package that quantifies the impact of vector control interventions depending on mosquito species and location-specific characteristics. In addition, it includes a previously published, comprehensive, curated database of field entomological data from over 50 Anopheles species, field data on mosquito and human behaviour, and estimates of vector control effectiveness. Using the input data, the package parameterizes a discrete-time, state transition model of the mosquito oviposition cycle and infers species-specific impacts of various interventions on vectorial capacity. In addition, it offers formatted outputs ready to use in downstream analyses and by other models of malaria transmission for accurate representation of the vector-specific components. Using AnophelesModel, we show how the key implications for intervention impact change for various vectors and locations. The package facilitates quantitative comparisons of likely intervention impacts in different geographical settings varying in vector compositions, and can thus guide towards more robust and efficient malaria control recommendations. The AnophelesModel R package is available under a GPL-3.0 license at https://github.com/SwissTPH/AnophelesModel.

Effect of Treatment of Malaria and Diabetes with Aqueous Extract of <i>Anthocleista Djalonensis</i> in Mice

Anthocleista djalonensis is a medicinal plant that has been used to treat malaria, jaundice, abscesses and diabetes. The study assessed the effects of aqueous extract of A. djalonensis leaves on some biochemical indices in the treatment of malaria and diabetes. Twenty-four mice used were randomly assigned into six groups numbering four each and provided with feed and water ad libitum. Group 1 (control) received water and feed only. Groups 2, 3, 4 5 and 6 received 200 mg/kg body weight of extract; 5 mg/kg body weight of chloroquine, 400 mg/kg body weight extract, 2 mg/kg body weight glibenclamide 5 mg/kg body weight chloroquine and 2 mg/kg body weight glibenclamide respectively for seven days. Phytochemical screening of A. djalonensis leaves revealed the presence of alkaloids, phenols, saponins, steroids, flavonoids and tannins at 6.76 ± 0.03, 0.61 ± 0.01, 2.11 ± 0.02, 0.89 ± 0.01, 3.10 ± 0.03 and 1.13 ± 0.01 % respectively. Alanine aminotransferase and aspartate aminotransferase activity of Groups 5 and 6 were significantly (p<0.05) higher compared to the control. There were no visible histological changes in liver and kidney. Results of this study suggest that A. djalonensis is relatively safe for the treatment of diabetes and malaria at the administered doses.

Highly oxygenated antiplasmodial and non-hemolytic Δ7,9(11) stigmastane-type steroids from the twigs of Vernonia amygdalina Delile

Chemical investigations of a methanolic extract of the twigs of Vernonia amygdalina Delile (Asteraceae) resulted in the isolation and identification of three previously undescribed highly oxygenated Δ7,9(11) stigmastane-type steroids namely vernonins U−W (1−3) along with six known compounds (4−9). The structural characterization of all the isolated compounds has been conducted via comprehensive 1D- and 2D-NMR spectroscopy as well as HRMS. The seven steroidal derivatives 1−7 were evaluated for their antiplasmodial activity against the chloroquine-resistant strain P. falciparum Dd2 (PfDd2) and their hemolytic effect on human red blood cells (RBCs). Vernonins U (1), A (4) and stigmasterol-3-O-β-D-glucopyranoside (7) showed the highest activity with IC50 values of (5.47 ± 0.01) μg/mL, (6.02 ± 0.13) μg/mL and (6.34 ± 0.80) μg/mL, respectively, against PfDd2, while vernonin W (3) showed moderate activity of (21.20 ± 0.40) μg/mL. None of the tested compounds displayed hemolytic effects on human RBCs up to 100 μg/mL indicating their safety. These results enrich the known chemistry of V. amygdalina and support its use in folk medicine for the treatment of malaria. This encourages further research towards new antiplasmodial drug candidates from this plant.

Comparative clinical study of Mist Amen Fevermix and Edhec Malacure: two polyherbal products used for the treatment of uncomplicated malaria in Ghana against Artemether/Lumefantrine

The use of herbal products for the treatment of malaria, has increased globally. However, inadequate scientific studies about the safety and effectiveness of such herbal products have been raised. Also, the reduced sensitivity of the malaria parasites to artemisinin-based combination therapies is of concern. There is therefore the need for new antimalarial medications including those from alternative sources such as herbal medicinal products. In this study, a prospective, comparative parallel group randomized, clinical study was done to assess the safety and effectiveness of Mist Amen Fevermix and Mist Edhec Malacure with Artemether/Lumefantrine as control at the Tafo Government Hospital, Kumasi between July and November 2019, after Committee on Human Research, Publication and Ethics approval (CHRPE/AP/424/19). The study was conducted in accordance with Good Clinical and Laboratory Practice (GCLP) and registered with the Pan African Clinical Trials Registry with trial number PACTR202109664146698. Participant completed an informed consent form. Randomization was based on a single sequence to allocate participants to a group. SPSS version 19. One-way ANOVA test and exploratory statistics was used for data analysis. Total sample size was 150 participants with 50 on each arm of the group. Male and female patients aged 15–45 years and meet inclusion criteria with clinically established malaria were treated with Mist Amen Fevermix and Mist Edhec Malacure, at the specified doses of 45 mls (0.1063 g) and 30 mls (0.0521 g) three times daily after meals for three days. Artemether/Lumefantrine was administered at a dose of 80/480 mg/kg twice daily after meals for three days. Baseline data was taken on day 0. Patients were then followed up on Day 3, 7 and 28 to establish treatment outcomes and any side effect using a checklist for signs and symptoms and Karnofsky’s scale to assess the quality of life. Mist Amen Fevermix was effective with a cure rate of 95.89%. Mist Edhec Malacure was also effective with a cure rate of 91.87%. The cure rate of Artemether/Lumefantrine was 97.25%. Kidney and liver panels were within normal reference range at the end of the 28-day study. This study supports the use of Mist Amen Fevermix and Mist Edhec Malacure, two multi-component products as safe and effective for the treatment of uncomplicated malaria. Both products achieved a comparable clinical treatment outcome with Artemether/Lumefantrine.

Protecting maternal health: Strategies against HIV and malaria in pregnancy.

Maternal health remains a global priority, with particular emphasis on combating infectious diseases such as HIV and malaria during pregnancy. Despite significant progress in prevention and treatment efforts, both HIV and malaria continue to pose significant risks to maternal and fetal well-being, particularly in resource-limited settings. The prevention of mother-to-child transmission (PMTCT) programs for HIV and intermittent preventive treatment (IPTp) for malaria represent cornerstone strategies in mitigating the impact of these infections on pregnancy outcomes. PMTCT programs focus on early HIV diagnosis, antiretroviral therapy initiation, and promoting safe infant feeding practices to reduce the risk of mother-to-child transmission. Similarly, IPTp involves the administration of antimalarial medication to pregnant women in malaria-endemic regions to prevent maternal and fetal complications associated with malaria infection. Integration of HIV and malaria prevention and treatment services within existing maternal and child health programs is crucial for maximizing impact and minimizing healthcare system strain. Strengthening health systems, improving access to antenatal care services, and enhancing community engagement are essential components of comprehensive maternal health strategies. Furthermore, promoting awareness, education, and empowerment of pregnant women and communities are vital in fostering health-seeking behaviors and adherence to preventive measures against HIV and malaria. In conclusion, protecting maternal health from the dual threat of HIV and malaria requires a multifaceted approach that encompasses prevention, screening, treatment, and community engagement.

Dengue and malaria coinfection in a traveling patient: Case study

Introduction: Dengue and malaria are two prevalent diseases in the tropics, transmitted by vectors, and cause different morbidity and fatality rates. However, coinfection of dengue and malaria is relatively rare but clinically significant, since both diseases can have severe manifestations and their coexistence complicate diagnosis and treatment. Clinical Case: The clinical case of a male patient, 32 years old, resident in Angola, who entered Ecuador twenty-one days prior to the onset of symptoms, with no history, was hospitalized for unquantified temperature rise, myalgia, arthralgia and fatigue. His clinical picture is exacerbated with abdominal pain in the right upper quadrant and generalized rash, BP: 105/58 mmHg, HR: 108 bpm, RR: 18 rpm, pulse oximetry 98%, T°: 38°C, dry oral mucosa, expansibility of the decreased chest, dysrhythmic heart, no murmurs, painful abdomen, absent fluid sounds, extremities without edema. The rapid antigen test performed was positive for Plasmodium falciparum, thick smear positive for Plasmodium falciparum. Discussion: The simultaneous treatment of malaria and dengue required careful monitoring of warning signs and possible complications; collaboration between health professionals from Ecuador and Angola was necessary for the successful management and handling of the patient.Conclusions: Documentation of such cases should influence health policies and the planning of preventive strategies, such as vaccination, vector control, and preventive education of travelers before visiting endemic areas.

Design and synthesis of pyrano[2,3-c]pyrazole-4-aminoquinoline hybrids as effective antimalarial compounds

In this work, a series of nineteen novel pyrano[2,3-c]pyrazole-4-aminoquinoline hybrids were synthesized as potent antimalarial agents by covalently linking the scaffolds of 4-aminoquinoline and pyrano[2,3-c]pyrazoles via an ethyl linker and characterized using Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). Molecular docking was used to test each hybrid's and standard chloroquine's ability to bind to Plasmodium falciparum lactate dehydrogenase enzyme (PfLDH), an important enzyme in the parasite's glycolytic pathway. The hybrid compounds had a stronger binding affinity than the standard chloroquine (CQ). The schizontical antimalarial test of pyrano[2,3-c]pyrazole-4-aminoquinoline hybrid compound shows that all nineteen hybrid compounds were potent with the IC50 values ranging from 0.0151 to 0.301 μM against the CQ-sensitive 3D7 P. falciparum strain, and were active against the CQ-resistant K1 P. falciparum strain with the IC50 values ranging from 0.01895 to 2.746 μM. All the tested hybrid compounds were less potent than the standard drug chloroquine dipaspate (CQDP) against the CQ-sensitive 3D7 strain. In contrast, nine of the nineteen hybrids (16d, 16g, 16h, 16i, 16l, 16n, 16o, 16r, and 16s) displayed superior antimalarial activity than the CQDP against the CQ-resistant K1 P. falciparum strain. Among all the tested hybrids, 16c against the 3D7 strain and 16h against the K1 strain were the most promising antimalarial agents with 0.0151 and 0.01895 μM of IC50 values, respectively. In addition, the compounds were selective, showing moderate to low cytotoxic activity against a human normal liver WRL68 cell line. The synthesis of pyrano[2,3-c]pyrazole-4-aminoquinoline hybrids introduces new chemical entities that have the potential to exhibit potent antimalarial activity. It could address the ongoing challenge of drug resistance in malaria treatment.

Uptake and Effectiveness of Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine during Pregnancy in Africa: A Scoping Review.

Malaria poses a significant threat to pregnant women in sub-Saharan Africa, necessitating effective interventions like the intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). However, challenges persist in the uptake and effectiveness of this intervention. This scoping review aims to explore IPTp-SP uptake in African countries, identify influencing factors, and assess its effectiveness in preventing malaria and adverse outcomes in pregnancy. This scoping review follows Arksey and O'Malley's framework, employing the PRISMA-ScR guidelines for reporting. Searches were conducted in PubMed, Embase, Scopus, JSTOR, Web of Science, Google Scholar, and ProQuest, focusing on studies post-2000 published in the English language. The search produced 15,153 records, of which 104 full-text records were eligible and 101 papers were included in this review. The findings suggest varying IPTp-SP uptake rates, spanning from 5.3% to 98.9%, with their effectiveness supported by longitudinal studies, randomised controlled-trials (RCTs), cross-sectional surveys, and mixed-method studies. IPTp-SP demonstrates efficacy in reducing malaria during pregnancy, placental parasitaemia, and anaemia episodes, alongside improved birth outcomes. Common adverse effects of IPTp-SP include prematurity and low birth weight. Facilitators of IPTp-SP uptake include education and ANC attendance, while commonly reported barriers included inadequate knowledge and healthcare system challenges. The findings also suggest adverse effects such as prematurity, low birth weight, and maternal and perinatal mortality associated with IPTp-SP uptake. It is vital to strengthen antenatal care services by integrating comprehensive counselling on IPTp-SP and address healthcare system challenges. Community engagement, women's empowerment, and context-specific interventions are necessary for promoting IPTp-SP uptake and improving maternal and neonatal health outcomes in Africa.

Toward Malaria Elimination: Understanding Awareness, Prevention, and Health-Seeking Patterns in Odisha, India.

Given India's goal of eliminating malaria by 2030, this study aimed to investigate community perspectives on malaria in highly endemic areas of Odisha, a region historically prone to malaria. The research explores self-reported malaria events, community knowledge, attitudes, practices, health-seeking behaviors, and access to healthcare services. A community-based cross-sectional survey conducted among 387 households between November 2022 and May 2023 served as an extension of our recent project, monitoring malaria elimination efforts in remote and challenging-to-reach communities in Odisha. The participants, who had a mean (SD) age of 41.7 (13.17) years, were predominantly male (88.4%). Self-reported malaria in the last 12 months prior to the survey was 6.2%, with half of the patients opting for primary health centers for treatment, averaging a 5-day recovery per episode. The median cost per malaria treatment episode was U.S. dollars 20.17. A significant majority (79.8%) demonstrated a strong awareness of malaria symptoms and transmission, with 83.3% expressing a favorable attitude toward disease prevention. Notably, 65.1% reported consistent use of long-lasting insecticidal nets. However, nearly half of the participants reported inadequate larval source management and indoor residual spraying services. Although there were slight variations in knowledge, attitude, and practice scores among demographic groups, the overall understanding of and approach to malaria were consistent in the study population, with no statistically significant differences (P >0.05). The study findings offer hope, suggesting that with sustained dedication and focused surveillance, malaria could become a thing of the past.

Population pharmacokinetics of amodiaquine and piperaquine in African pregnant women with uncomplicated Plasmodium falciparum infections.

Artemisinin-based combination therapy (ACT) is the first-line recommended treatment for uncomplicated malaria. Pharmacokinetic (PK) properties in pregnant women are often based on small studies and need to be confirmed and validated in larger pregnant patient populations. This study aimed to evaluate the PK properties of amodiaquine and its active metabolite, desethylamodiaquine, and piperaquine in women in their second and third trimester of pregnancy with uncomplicated P. falciparum infections. Eligible pregnant women received either artesunate-amodiaquine (200/540 mg daily, n = 771) or dihydroartemisinin-piperaquine (40/960 mg daily, n = 755) for 3 days (NCT00852423). Population PK properties were evaluated using nonlinear mixed-effects modeling, and effect of gestational age and trimester was evaluated as covariates. 1071 amodiaquine and 1087 desethylamodiaquine plasma concentrations, and 976 piperaquine plasma concentrations, were included in the population PK analysis. Amodiaquine concentrations were described accurately with a one-compartment disposition model followed by a two-compartment disposition model of desethylamodiaquine. The relative bioavailability of amodiaquine increased with gestational age (1.25% per week). The predicted exposure to desethylamodiaquine was 2.8%-32.2% higher in pregnant women than that reported in non-pregnant women, while day 7 concentrations were comparable. Piperaquine concentrations were adequately described by a three-compartment disposition model. Neither gestational age nor trimester had significant impact on the PK of piperaquine. The predicted exposure and day 7 concentrations of piperaquine were similar to that reported in non-pregnant women. In conclusion, the exposure to desethylamodiaquine and piperaquine was similar to that in non-pregnant women. Dose adjustment is not warranted for women in their second and their trimester of pregnancy.

In vitro antibacterial, antioxidant, in silico molecular docking and ADEMT analysis of chemical constituents from the roots of Acokanthera schimperi and Rhus glutinosa

Acokanthera schimperi is a medicinal plant traditionally used for the treatment of wounds, scabies, and malaria. Rhus glutinosa has been also utilized for the management of ectoparasites and hemorrhoids. Silica gel column chromatography separation of CH2Cl2/MeOH (1:1) extract root of A. schimperi afforded oleic acid (1), lupeol (2), dihydroferulic acid (3), acovenosigenin A- 3-O-α-L-rhamnopyranoside (4) and sucrose (5) whereas CH2Cl2/ MeOH (1:1) and MeOH roots extracts of R. glutinosa afforded β-sitosterol (6), (E)-5-(heptadec-14-en-1-yl)-4,5-dihydroxycyclohex-2-enone (7), methyl gallate (8), and gallic acid (9). The structures of the compounds were established using spectroscopic (1D and 2D NMR) and FT-IR techniques. Disc diffusin and DPPH assay were used, respectively, to evaluate the antibacterial and antioxidant potential of the extracts and isolated compounds. MeOH extract root of A. schimperi showed a modest antibacterial effect against E.coli with an inhibition zone (ZI) of 16 ± 0.0 mm compared to ciprofloxacin (ZI of 27.0 ± 0.0 mm). CH2Cl2/MeOH (1:1) and MeOH root extracts of R. glutinosa showed maximum activity against S. aureus with ZI of 17.3 ± 0.04 and 18.0 ± 0.0 mm, respectively. At 5 mg/mL, the highest activity was noted against S. aureus by 8 with ZI of 18.6 ± 0.08 mm. Dihydroferulic acid (3), methyl gallate (8), and gallic acid (9) displayed potent scavenging of DPPH radical with respective IC50 of 10.66, 7.48, and 6.08 µg/mL, compared with ascorbic acid (IC50 of 5.83 µg/mL). Molecular docking results showed that lupeol (2) exhibited strong binding energy of -7.7 and − 10 kcal/mol towards PDB ID: 4F86 and PDB ID: 3T07, respectively, compared to ciprofloxacin (-6.5 and − 7.2 kcal/mole). Towards PDB ID: 1DNU receptor, compounds 3, 8, and 9 showed minimum binding energy of -5.1, -4.8, and − 4.9 kcal/mol, respectively, compared to ascorbic acid (-5.7 kcal/mol). The Swiss ADME prediction results indicated that compounds 2, 3, 8, and 9 obeyed the Lipinksi rule of five and Veber rule with 0 violations. The in vitro antibacterial and antioxidant results supported by in silico analysis indicated that compounds 2, 3, 8, and 9 can potentially be lead candidates for the treatment of pathogenic and free radical-induced disorders.

Community-based strategies to increase coverage of intermittent preventive treatment of malaria in pregnancy with sulfadoxine–pyrimethamine in sub-Saharan Africa: a systematic review, meta-analysis, meta-ethnography, and economic assessment

Community-based approaches might increase uptake of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). We assessed the effects of community-based approaches on IPTp-SP and antenatal care coverage, and barriers and facilitators to implementation in sub-Saharan Africa. We did a systematic review, meta-analysis, meta-ethnography, and economic assessment. We searched the WHO International Clinical Trials Registry Platform, PubMed, the Malaria in Pregnancy Library database, Medline, Global Health and Global Health Archives, and the Cochrane Library for trials, mixed-methods, qualitative, and cost-effectiveness studies of community health worker promotion of antenatal care, IPTp-SP delivery, or both, with no language restrictions, published before March 21, 2024. Information on interventions, number of IPTp-SP doses, antenatal care visits, and barriers and facilitators were extracted. We did a meta-analysis (random effects) comparing effects on two or more or three or more IPTp-SP doses and one or more or four or more antenatal care visits. We followed Noblit and Hare's method of meta-ethnography to synthesise qualitative findings, using reciprocal translation and line-of-argument synthesis. We developed a theory for increased community IPTp-SP uptake. We also summarised cost and cost-effectiveness studies. This study is registered with PROSPERO, CRD42022364114. Of 4753 records screened, we included 23 (0·5%) reporting on 15 studies. Community health worker involvement was associated with an increase in two or more IPTp-SP doses (pooled risk ratio 1·48, [95% CI 1·24-1·75]; 12 sub-studies; I2 94·7%) and three or more IPTp-SP doses (1·73 [1·19-2·50]; ten sub-studies, I2 97·5%), with no decrease in four or more antenatal care visits (1·17 [1·00-1·36]; 13 sub-studies; I2 90·3%). Cluster-randomised controlled trials showed a lower increase in coverage of three or more IPTp-SP doses (1·08 [1·00-1·16]; I2 0·0%; six studies) compared with before-and-after studies (2·86 [1·29-6·33]; I2 98·9%; four studies; subgroup analysis p=0·019). Barriers to community health worker delivery of IPTp-SP included women's fear of side-effects, lack of knowledge, lack of trust in community health workers, and sociocultural factors. Community sensitisation, engagement of husbands, pre-established community health worker networks, and trained and supported community health workers facilitated IPTp-SP delivery by community health workers. Incremental cost-effectiveness ratios ranged from $1·1 to $543 per disability-adjusted life-year averted. Community-based approaches increased IPTp-SP coverage and might have a positive effect on the number of antenatal care visits in addition to being cost-effective, although we found high heterogeneity among studies. Community sensitisation and engagement in addition to established, trained, and supported community health workers can facilitate acceptability, delivery, and uptake of IPTp-SP delivered by community health workers. EDCTP-2 supported by the European Union. For the French translation of the abstract see Supplementary Materials section.