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Systematic biochemical and cheminformatic evaluation of the gametocytocidal activity of antimalarial lead candidates
Published 2024Subjects: “…Antimalarial compound…”
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Nmr-based metabolomic study of medicinal plants used against malaria and the isolation of bioactive alkaloids
Published 2016Subjects: “…Antimalarial plants…”
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Page will reload when a filter is selected or excluded.- AMFm-ACTs 1 results 1
- Adherence to current treatment guidelines on prescription of antimalarials by healthcare providers can promote better malarial treatment outcomes. However, adherence rate and factors influencing adherence to treatment guidelines have not been well explored. This study was carried out to assess adherence to current guidelines on prescription of antimalarials and associated factors among healthcare providers in Lokoja Local Government Area, Kogi State, Nigeria. The study was cross-sectional in design. A total of 404 healthcare providers aged 18-65 years were selected through proportional allocation from public health facilities and patent medicine stores. Using a semi-structured, interviewer-administered questionnaire, data were collected on socio-demographic characteristics of respondents, knowledge and training on current guidelines and prescription practice. Adherence was defined as correct prescription of artemisinin-based combination therapy for uncomplicated malaria in a child and adult. Knowledge of current guidelines was assessed on a 5-point scale and scores ≥3 were categorised as good knowledge while scores <3 were categorised as poor. Data were analysed using descriptive statistics, Chi-square test and logistic regression with significance level set at 0.05. Mean age of respondents was 36.9 years (SD = 9.2 years). Respondents comprised of nurses (36.6%), patent medicine vendors (30.0%), doctors (18.3%), community health extension workers (9.7%), pharmacists (3.2%) and community health officers (2.2%). Over half (53.0%) were males and about three-quarters (74.4%) were married. Half (50.0%) had good knowledge of the guidelines of which 34.2% were doctors and 4.0% each were community health officers and pharmacists. A total of 270 (66.8%) of respondents claimed they requested for confirmatory test before treatment of malaria. In all, 54.2% had been trained on the guidelines of which 36.1% were patent medicine vendors while only 1.4% was pharmacists. Overall adherence to guidelines on anti-malaria prescription was 39.6%. The adherence among doctors was 67.6%, community health officers (55.6%), pharmacists (19.8%). Respondents who were trained on the guidelines were twice more likely to adhere to guidelines. (AOR=2.28; CI=1.41-3.69) while respondents with good knowledge were four times more likely to adhere to guidelines compared to those with poor knowledge (AOR=3.99; CI=2.39-6.69). Knowledge of and adherence to current guidelines on antimalarials prescription was generally low in Lokoja among community health officers, nurses, pharmacists and patent medicine vendors in the study. Government should train these categories of health care providers to improve their knowledge and adherence to the guidelines. Keywords: Treatment guidelines, Antimalarial prescription, Health care providers, Malaria confirmatory test. Word count: 384 1 results 1
- Amodiaquine 1 results 1
- Anacardium occidentale L 1 results 1
- Antimalarial Drug Utilization 1 results 1
- Antimalarial Treatment Guidelines 1 results 1
- Antimalarial activity 1 results 1
- Antimalarial prescription 1 results 1
- Antimalarial tablets 1 results 1
- Antimalarials 1 results 1
- Artemisinin Combination Therapy 1 results 1
- Awareness and Access 1 results 1
- Caregivers of Under-Five Children 1 results 1
- Crinum jagus 1 results 1
- Crinum jagus is a medicinal plant used traditionally to treat tuberculosis, malaria and other bacterial infections. However, there are limited documented scientific studies to substantiate the use of this plant. Due to increase in resistance to malaria and tuberculosis drugs, the need for the development of other drugs is pertinent. This study was designed to determine the pharmacological activities of extract and fractions of Crinum jagus. Methanol extract of C. jagus obtained by soxhlet extraction was subjected to phytochemical analysis and fractionated using column chromatography. Antitubercular and antimicrobial activities of the extract and its fractions were evaluated against isolates of Mycobacterium tuberculosis and selected microorganisms using the disc and agar diffusion methods. Antimalarial activity was assessed in vivo using Rane’s test in Plasmodium berghei infected mice (n = 80 in 10 groups) treated orally with tween 80 (control), 10, 25, 50 and 75 mg/kg of extract and its fractions at 10 mg/kg respectively, while chloroquine (10 mg/kg) and arteether (3 mg/kg) groups served as positive controls. Anti-inflammatory potential was assessed in rats using carrageenan-induced paw inflammatory model. In vitro antioxidant potentials were determined spectrophotometrically using 1,1-diphenyl-2-picryl hydrazyl (DPPH), hydroxyl radical scavenging activities, Total Flavonoids Contents (TFC) and Phenolic Contents (TPC) Antioxidant indices- Superoxide dismutase (SOD) and Catalase (CAT) activities and levels of Malondialdehyde (MDA) and reduced Glutathione (GSH) were determined by spectrophotometry. Aspartate (AST) and Alanine (ALT) amino transferases and Alkaline Phosphatase (ALP) were estimated spectrophotometrically. Data were analysed by Student’s t test at p = 0.05. Phytochemical analysis revealed the presence of alkaloids, flavonoids, phenols and steroids in the crude extract. The extract and its fractions (F1, F2 and F3) showed a concentration- dependent inhibition of Mycobacterium tuberculosis, with F1 having the lowest IC50of : 0.22mg/mL relative to rifampicin (IC50 : 0.19mg/mL) and isoniazid (0.23mg/mL). The extract at 10, 25, 50, 75 mg/kg and F1, F2 and F3 at 10 mg/kg suppressed parasitaemia in Plasmodium berghei infected mice by 70.0, 76.0, 79.0, 87.0% and 89.0, 76.0, 78.0% respectively relative to chloroquine (100%) and arteether (89.0%). The extract at 10, 25, 50, 75 mg/kg and F1, F2 and F3 at 10 mg/kg inhibited oedema in rat paws by 26.0, 30.0, 32.0, 66.0% and 80.0, 25.0, 52.0% UNIVERSITY OF IBADAN LIBRARY iii respectively when compared with indomethacin (95.0%). The extract and its fractions significantly scavenged DPPH and hydroxyl radical in vitro. The TPC and TFC of extract, F1, F2 and F3 at 500 μg/ml were 0.310, 0.460, 0.240, 0.380 μg/mg and 0.523, 0.864, 0.396, 0.643 μg/g respectively. The extract and its fractions significantly reduced MDA level while GSH, SOD and CAT levels were increased. Activities of AST, ALT and ALP were significantly increased at 50 and 75 mg/kg body weight of extract . Crinum jagus exhibited antitubercular, antimalarial and anti-inflammatory activities via scavenging of radicals and antioxidative mechanism. This indicates a promising potential of the plant for drug development. Keywords: Crinum jagus, antituberculosis, antimalarial, antioxidant. Word Count: 471 . 1 results 1
- Distribution of Affordable Medicine Facility-malaria Artemisinin CombinationTherapies (AMFm-ACTs) started in Nigeria in 2011, but its use at community level has not been documented. Methods. Four hundred seventy-eight caregivers whose under-five children had fever within two weeks prior to the survey were selected using cluster sampling technique. Information on sociodemographic characteristics, treatment seeking for malaria, and awareness and use of AMFm-ACTs was collected using an interviewer administered questionnaire. Result. More than half of the respondents (51.2%) bought AMFm-ACTs without prescription. Awareness of AMFm was low as only 9.1% has heard about the programme. Overall, 29.2% used AMFm-ACTs as their first line choice of antimalarial drug. On bivariate analysis age, group (25–34 years), public servants, respondents with tertiary education, respondents with high socioeconomic status, respondents with poor knowledge of symptoms of malaria, awareness of AMFm-ACTs, availability of AMFm-ACTs, and sources of drug were significantly associated with utilization of AMFm-ACTs (𝑃 < 0.05). Logistic regression demonstrated that only people who were aware of AMFM-ACTs predicted its use (AOR: 0.073; CI: 0.032–0.166; 𝑃 < 0.001). Conclusion. Interventions which targeted at raising awareness of AMFm-ACTs among people at risk of malaria are advocated for implementation. 1 results 1
- Drug bioavailability 1 results 1
- Drug resistance is a challenge to malaria control efforts and several factors including parasite genetics, host factors and pharmacokinetics may contribute to the selection of drug resistant Plasmodium falciparum. Understanding the role of these factors in patient response to antimalarial drugs is therefore essential in the management of malaria. The aim of the study was to determine the factors contributing to delay in malaria Parasite Clearance (PC) in children and evaluating the effects of pharmacokinetic variability on treatment outcome. Children (n=2,752), aged 6 months -12 years, with falciparum malaria, were enrolled over a period of eight years and treated with standard doses of Chloroquine (CQ), Sulphadoxine-Pyrimethamine (SP) or Amodiaquine (AQ) given alone or in combination with artemisinin. Each patient was followed up for at least 14 days. Age, axillary temperature, parasite density and gametocytaemia were assessed for their potential association with delay in PC and treatment outcomes. Filter-paper blood samples were collected from some of the children (n=148) before treatment and on days 1-7, 14, 28 and 35 after treatment for determination of CQ and sulphadoxine concentrations. In another subset of patients (n=7), treated with amodiaquine, blood and saliva samples were collected over 35 days. High performance liquid chromatographic techniques were used to determine concentrations of sulphadoxine in whole blood as well as AQ and Desethyl amodiaquine (DEAQ) in saliva. Mean maximum drug concentration (Cmax), half-life (t1/2) and area under concentration-time curve (AUC0-28d) were assessed for their association and predictive value for treatment outcomes. Data were analyzed using descriptive statistics, ANOVA, Chi-square, Students’ t-test, Kruskal-Wallis and multiple regressions at p = 0.05. Age ≤ 2 years (Adjusted odds ratio [AOR] = 2.13), presence of fever (AOR = 1.33) and parasitaemia > 50,000/µl (AOR = 2.21) at enrolment were independent risk 3 factors for delay in PC, while a body temperature >38OC and parasitaemia >20,000/µl were predictors a day after treatment regardless of the drug used. Day 3 concentration ≤ 1750ng/ml and AUC0-28d ≤ 950ng/ml.h were associated with chloroquine treatment failure. In a multivariate analysis, a terminal elimination t½ ≤ 220h (AOR = 0.28) and AUC0-28d ≤ 950ng/ml.h (AOR = 4.12) were identified as independent pharmacokinetic predictors of chloroquine treatment failure. Age stratified analysis showed that SDX concentrations were significantly higher in children > 5years compared to children <5years: Cmax; 295 vs 125µg/ml, AUC0-28d; 1562 vs 812µg/ml.d. In patients who received AQ, there was a rapid conversion of AQ to DEAQ, which was detectable in plasma and saliva within 40 minutes of administration. The mean day 7 concentration of DEAQ was significantly higher in plasma than in saliva (247.8 vs 125.1ng/ml). The t1/2 of DEAQ were similar in plasma (167.25±43.4h) and saliva (146.12±17.2h). The decline phases of DEAQ in saliva concentration-time curves were approximately similar to that in plasma. Delay in parasite clearance is specific and related to drug resistance. In addition pharmacokinetic variability of sulphadoxine in children has potential impact on dosage regimen and treatment outcome. 1 results 1
- Health care providers 1 results 1
- Malaria Treatment 1 results 1
- Malaria confirmatory test 1 results 1
- Malaria is one of the most devastating parasitic diseases in the world and remains a major public health problem in Sub-Saharan Africa. First-line treatment of uncomplicated malaria includes the use of artesunate and amodiaquine. However, the existence of counterfeit and substandard artesunate and amodiaquine in the market may lead to therapeutic failures or development of resistance when consumed. The aim of the study was to examine the pharmaceutical equivalence of different brands of artesunate and amodiaquine tablets and, their bioavailability and tolerability when given as monotherapy and combination therapy. Fifteen brands of artesunate and five brands of amodiaquine tablets selected randomly were obtained from retail drug outlets in Ogun, Oyo and Lagos states in South western Nigeria and were subjected to various physicochemical tests including drug content, disintegration and dissolution times. The bioavailability after oral administration of single doses of artesunate (200mg), amodiaquine (600mg), their fixed combination (200mg/612.6mg), and non-fixed combination (200mg+600mg) as measured by high performance liquid chromatography of plasma samples and tolerability were compared. Sixteen healthy male volunteers aged between 18 and 45 years distributed into four groups received treatments at four different occasions in an open label, Latin square, 4-phase, cross-over study. Absorption was determined from area under the plasma drug concentration-time curves (AUC), peak plasma concentration (Cmax) reached and time taken to reach peak plasma concentration (Tmax). Impairment of absorption was indicated by at least one statistically significant parameter. Biochemical test was measured using serum albumin while body fat was derived from the body mass index. Data collected from physicochemical tests were evaluated using correlation and Chi square analyses while those of serum albumin and body fat, parent drugs and their main metabolites(dihydroartemisinnin and desethylamodiaquine) were assessed using logistic regression, Students’ t-test and ANOVA. Physicochemical tests revealed that 33.0% of the artesunate tablets and 80.0% of the amodiaquine tablets analyzed met compendial standards. Minimum absorption occurred when tablets were given as monotherapy and in combination. The bioavailability of artesunate when given in fixed combination with amodiaquine was lowered (Cmax ratio-76.4%, p<0.001) compared with monotherapy. Taking amodiaquine in fixed combination with artesunate markedly increased its bioavailability (AUC ratio-159.9%, p<0.001) when compared with monotherapy. However, concurrent administration of artesunate in non-fixed combination with amodiaquine reduced its bioavailability (Tmax ratio-209.7%, p<0.001) when compared with monotherapy. The bioavailability of amodiaquine was about twice as high when given in non-fixed combination (AUC ratio-195.4%, p<0.05) compared with monotherapy. Adverse events of concern were anaemia (81.25%), asthenia (62.5%) and neutropenia (25%). Asthenia was largely correlated with serum albumin in volunteers that took fixed dose combination (OR=9.3, p<0.05). Adverse effects were increased in volunteers that had higher body fat percentage (OR= 0.571, p>0.05). Pharmaceutically inequivalent and subpotent artesunate and amodiaquine tablets are in circulation in Southwestern Nigeria and this suggests the need for regulatory authorities to rigorously monitor their quality. There was severe impairment of rate and extent of absorption as a result of co-administration of the drugs. It is therefore recommended that artesunate should not be coadministered with amodiaquine in clinical setting. 1 results 1
- Pharmaceutical equivalence 1 results 1
- Pharmacokinetics 1 results 1
- Physicians compliance 1 results 1
- Plasmodium berghei 1 results 1
- Plasmodium falciparum 1 results 1
- Psidium guajava L 1 results 1
- The National Antimalarial Treatment Guidelines (NATG) stipulates treatment actions for the management of malaria using Artemisinin Combination Therapy (ACT). Available evidence indicates that adoption of treatment guidelines are not matched with corresponding levels of comprehension and compliance. An investigation of practice gaps will generate information which will guide future policy formulation and implementation. The aim of this study was to determine the factors influencing compliance of facility-based secondary health care physicians in Oyo state with NATG. This descriptive cross-sectional study involved 94 out of 124 physicians on full-time employment from all 36 secondary health care facilities offering malaria management services in Oyo state. They were interviewed using a semi-structured interviewer-administered questionnaire to elicit information on awareness of and perceived challenges relating to implementation of the NATG. This included a 60-point knowledge scale on diagnosis and treatment of malaria with knowledge scores of 0-20, >20-40 and >40-60 rated as poor, fair and good respectively. Case notes of malaria patients seen on the day of interview were stratified into three categories; under-five children, pregnant women and adults. A minimum of one and maximum of three case notes were randomly selected across the strata per physician. Overall, 44, 74 and 128 case notes belonging to pregnant women, under-five children and adults respectively were assessed using a check-list which included an 11-point compliance scale on patient’s history documented, laboratory assessment and drug prescribed by dosage. Compliance scores of 0-3, >3-7 and >7-11 were rated poor, fair and good respectively. Data were analysed using descriptive statistics and t-test at p=0.05. Age of respondents was 40.0±8.6 years, 70.2% were males and mean years of experience was 9.4±3.4. Majority (84.0%) of the respondents had ever received training on NATG, 91.5% of the respondents had heard of the NATG mainly from medical conferences. However, 48.9%, 37.2% and 11.7% had seen, read and have personal copies of NATG respectively. Knowledge score was 32.4±6.4 with 8.5% and 90.4% of respondents having good and fair knowledge of the NATG respectively. Compliance score was 4.3±1.9 with 4.5%, 63.4% and 32.1% of physicians having good, fair and poor compliance respectively. Only 0.8% of case notes had complete history documented, 54.0% had prescription for ACT, 19.1% Sulphadoxine Pyrimethamine and 26.9% non-recommended Anti-Malarial Drugs. Recommended dosage of ACT was correctly prescribed in 26.0% and 47.8% of case notes belonging to children and adults respectively. Only 24.2% of adults and 5.6% of children had both clinical and laboratory assessments before prescription. High cost (31.4%), unavailability (14.9%) and treatment inefficacy (9.1%) of ACTs were identified as perceived hindrances to compliance with NATG. A statistically significant higher compliance score (4.4±1.7) was observed amongst respondents ever trained on NATG than those never trained (3.7±1.3). An interplay of factors influenced physician’s compliance with the national antimalarial treatment guidelines. Continuing professional training programmes on compliance with current malaria treatment approaches and adequate supervision are recommended. 1 results 1
- The antiplasmodial activities of Anacardium occidentale L. and Psidium guajava L. have been severally reported in literature. β--hematin production is an exclusive method implemented by Plasmodium protozoan parasite to produce very high quantities of redox active free hemoglobin. The purpose of this study is to determine the effectiveness of methanol extracts of Anacardium occidentale L. and Psidium guajava L. leaves used to treat severe malaria attacks in Nigeria and their impact on the inhibition of β-hematin production. The LD50 values for the leaves of Psidium guajava L. and Anacardium occidentale L. in methanol extracts were >5000 mg/kg and 1600 mg/kg, respectively. On Day 4, Plasmodium berghei-infected mice (NK 65) displayed comparable chemo-suppression of parasitaemia for A. occidentale (73.88%) and P. guajava (72.75%). However, both extracts had lower activities than chloroquine (83.58 %; 20 mg/mL). A. occidentale had a higher inhibition of formation of β hematin, with IC50 of 36.1 ± 0.52 µg/mL than P. guajava with IC50 of l0.25 ± 0.07 µg/mL and chloroquine with IC50 of 2.71±0.39 µg/mL. According to the current study, methanol extracts of the leaves of Anacardium occidentale L. and Psidium guajava L. have similar antimalarial effects and are associated with a reduction in β-hematin production. The in vivo antimalarial activity of Psidium guajava L. and Anacardium occidentale L. were equivalent, but Psidium guajava L. possessed a more potent inhibitor of the production of β-hematin. 1 results 1
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