Interactions of Aurein with Model Membranes and Antimalarials

Aurein is a cationic antimicrobial peptide, rich in phenylalanine residues. Although the peptide has been extensively studied, its mechanism of action is not fully understood and has not been established. This project is focused on studying the interactions of aurein with model biological membranes and antimalarials using Fourier Transform Infrared (FTIR), fluorescence, dynamic light scattering (DLS), atomic force microscopy (AFM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) techniques. FTIR data revealed conformational changes to the secondary structure of the peptide in the presence of the model membranes. The strongest interactions of aurein were found with DOPC and lipid raft systems. Fluorescence data revealed some differences in the mechanism of interaction between aurein and lipid rafts. Topographical analysis was performed using atomic force microscopy (AFM). AFM images of the peptide with its lipid rafts showed a change in surface roughness suggesting a different mechanism of interaction. DLS data in agreement with FTIR confirmed that aurein interacts differently with the lipid rafts. The results gathered from this study provided new insights on the interaction of aurein. On the other hand, drug-drug interaction issues continue to present a major dilemma for the clinician caring for complex patients such as those infected with infectious disease. This study has examined the interaction of aurein with quinine, primaquine, and chloroquine. Significant interactions between aurein and antimalarials occured at a higher concentration of antimalarials. Interactions between aurein and anti-malarials reveal a strong interaction between aurein and primaquine. Interactions between aurein and quinine or chloroquine were found to be weak and negligible. FTIR, TGA, and DSC may be used in a complementary way to gain insights into the possible drug-drug interactions involving aurein. These studies are needed to initiate in vivo controlled interaction studies between antibiotics and antimalarials.

Availability of Antimalarial Medicines in Community Pharmacies of Lusaka District, Zambia: Implications on Compliance to Malaria Treatment Guidelines

Background: Malaria remains a major cause of morbidity and mortality in Zambia, affecting all levels of society, with children under the age of five and pregnant women being most at risk of serious illness. The availability of antimalarial medicines is one of the key interventions of malaria management. This study assessed the availability of antimalarial medicines in community pharmacies in Lusaka district, Zambia. Materials and Methods: This was a cross-sectional study that was conducted among 210 community pharmacies from September to November 2022 using a well-structured checklist in selected areas of Lusaka district. The availability was verified by a physical check of the product. The checklist contained the medicines listed both in the guidelines for diagnosis and treatment of malaria in Zambia as well as in the World Health Organization (WHO) malaria treatment guidelines. Results: This study found that all antimalarials listed in the local treatment guidelines for malaria were available in community pharmacies, though with the varying distribution. Of the 210 community pharmacies, 209 (99.5%) had artemether/lumefantrine in stock. The lowest available antimalarial was quinine/clindamycin, which was only available in 3 (1.4%) of the outlets. Conversely, 3 out of 16 (18.8%) antimalarials that were available in community pharmacies were not listed in the local treatment guidelines of malaria in Zambia, despite being listed in the WHO malaria treatment guidelines. This translated into a compliance level of 81.2% based on the local malaria treatment guidelines. Conclusion: This study concluded that antimalarials were available for all categories of malaria management in community pharmacies, though with a varying distribution. The presence of antimalarials not listed in the Zambian treatment guidelines is of public health concern which may have an impact on antimicrobial resistance in the future.

Designing Artemisinins with Antimalarial Potential, Combining Molecular Electrostatic Potential, Ligand-Heme Interaction and Multivariate Models

Artemisinins tested against W-2 strains of malaria falciparum are investigated with molecular electrostatic potential (MEP), in an attempt to identify key features of the compounds that are necessary for their activities, as well as to investigate likely interactions with the receptor in a biological process and to use that information to propose new molecules. In order to discover the best geometry involving the ligand-receptor complexes (heme) studied and help in the proposition of the new derivatives, molecular simulations of interactions between the most negative charged region around the peroxide and heme locates (the ones around the Fe2+ ion) were carried out. In addition, PCA (principal components analysis), HCA (hierarchical cluster analysis), SDA (stepwise discriminant analysis), and KNN (K-nearest neighbor) multivariate models were employed to investigate which descriptors are responsible for the classification between the higher and lower antimalarial activity of the compounds, and also this information was used to propose new potentially active molecules. The information accumulated in studies of MEP, molecular docking, and multivariate analysis supported the proposal of new structures with potential antimalarial activities. The multivariate models constructed were applied to the new structures and indicated numbers 19 and 20 as the most prominent for syntheses and biological assays.

In vitro Potentiation of Antimalarial Activities by Daphnetin Derivatives Against Plasmodium falciparum

Objective To screen the antimalarial compounds of daphnetin derivatives against Plasmodium falciparum in vitro. Method Plasmodium faciparum （FCC1） was cultured in vitro by a modified method of Trager and Jensen. Antimalarial compounds were screened by microscopy-based assay and microfluorimetric method. Results DA79 and DA78 showed potent antimalarial activity against Plasmodiumfalciparum cultured in vitro. Conclusion Though the relationship between the structures of daphnetin derivatives and their antimalarial activities has not been clarified yet, this study may provide a new direction for discovery of more potential antimalarial compounds.

Antimalarial activity and toxicity of Garcinia mangostana Linn.

Objective:To investigate the antimalarial activity and toxicity of the crude ethanolic extract of its pericarp both in vitro and in vim.Methods:The antimalarial activity of Gareinja mangostana(G.mangostana)Linn.extract against 3D7 and Kl Plasmodium falciparum(P.falciparum)clone were assessed using SYBR green I-based assay.A 4-day suppressive test of Plasmodium berghei{P.berghei)infected mouse was performed to investigate in vivo antimalarial activity.Results:The in vitro antimalarial activity was seleclive(SI>5?and classified as weak and good lo moderate activity against both 3D7 and K1 P.falciparum,clones with median IC_(50)(range)values of 11.12(10.94-11.29)and 7.54(6.80-7.68)μg/mL,respectively.The extract was considered nontoxic to mice.The maximum tolerated doses for acute and subacute toxicity in mice were 5 000and 2 000 mg/kg,respectively.Median(range)parasite density on day 4 of the negative control group(25%Tween-80),mice treated with 250,500,1000,and 2 000 mg/kg body weight of the extract,and 10 mg/kg body weight of chloroquine for 14 d were 12.8(12.2-13.7),11.4(9.49-13.8),11.6(9.9-12.5),11.7(10.6-12.8),10.9(9.4-11.6)and 0(0-0)%respectively.Parasite density on day 4in the control group treated with Tween-80 was higher than the groups treated with chloroquine and all dose levels of the extract.Conclusions:G.mangostana linn,showed weak antimalarial activity of the extract both in vitro and in vivo could be due to limitation of absorption of the active compounds.

Isolation of antileishmanial,antimalarial and antimicrobial metabolites from Jatropha multifida

Objective:To investigate the antileishinanial,antimicrobial and antimalarial activities of the pure metabolites from Jatropha multifida used in African ethnomedicine.Methods:The methanolic stem bark extract of Jatropha multifida used in Nigerian folk medicine as remedy against bacterial infections was subjected to column chromatography and HPLC analyses lo obtain three known metabolites,microcyclic lathyrane dilerpenoids(1-3).Structures were confirmed by comparison of 1D and 2D spectral data with literature.Results:The three compounds exhibited inhibition of antileishmanial,antimalarial and antimicrobial actions against the tested organisms with compouds 2 and 3 active against Cryptococcus neoformans at IC_(50)of 82 and 8.7 μg/ml,respectively.Conclusions:The research lends support to the ethnomedicinal use of the plant in combating microbial infections,leishmaniasis and malarial infections.

Ethnobotanical survey of antimalarial plants in Awash-Fentale District of Afar Region of Ethiopia and in vivo evaluation of selected ones against Plasmodium berghei

Objective: To document plants used in traditional treatment of malaria in the Awash-Fentale District, the Afar Region of Ethiopia, and to evaluate antimalarial activity of selected ones against Plasmodium berghei in mice. Methods: Semi-structured interviews were carried out with purposively selected informants in the District to gather information on plants used in the traditional treatment of malaria. Standard procedures were used to investigate acute toxicity and a four-day suppressive effect of crude aqueous and ethanol extracts of the leaves of the two most frequently cited plants [Aloe trichosantha(A. trichosantha) and Cadaba rotundifolia(C. rotundifolia)] against Plasmodium berghei in Swiss albino mice. Results: The informants cited a total of 17 plants used in the traditional treatment of malaria in Awash-Fentale District. Plant parts were prepared as infusions or decoctions. Leaf was the most commonly cited(44%) plant part, followed by stem(22%). Shrubs were the most frequently cited(63%) medicine source followed by trees(21%). Of the 17 plants, C. rotundifolia and A. trichosantha were the most frequently mentioned plants in the district. Ethanol extracts of the leaves of C. rotundifolia and A. trichosantha suppressed P. berghei parasitaemia significantly accounting for 53.73% and 49.07%, respectively at 900 mg/kg. The plants were found to be non-toxic up to a dose of 1 500 mg/kg. Conclusions: Seventeen plant species were reported to be used for treatment of malaria in the Awash Fentale Distinct, among which A. trichosantha and C. rotundifolia were the most preferred ones. P. berghei suppressive activity of these plants may partly explain their common use in the community.

Antimalarial activity of the aqueous extract of Euphorbia cordifolia Elliot in Plasmodium berghei-infected mice

Objective:To evaluate the antimalarial activity of the aqueous extract of Euphorbia(E.)cordifolia Elliot against Plasmodium(P.)berghei-infected mice.Methods:Thirty healthy Swiss mice were intraperitoneally inoculated with 200μL of P.berghei parasitized-erythrocytes and divided into five groups,and then daily treated for 5 d with single dose of 10 mL/kg of distilled water for malaria control,10 mg/kg of chloroquine for the chloroquine control and 100,200 and 400 mg/kg of the aqueous extract of E.cordifolia for the three test groups.Parasitaemia was monitored by Giemsa-staining.At the end of the treatment,animals were sacrificed,and blood was collected for haematological and biochemical analyses.Organs were collected for biochemical and histopathological analyses.Statistical significance(P<0.05)was evaluated by analysis of variance followed by the Tukey post-test using Graphpad prism 7.0.Results:E.cordifolia extract decreased the parasite load to 2.46%,with an effective dose(ED50)of 113.07 mg/kg compared to the malaria group where the parasite load increased to(46.46±10.28)%.E.cordifolia extract prevented hypoglycaemia,anaemia,leucocytosis and thrombocytopenia,attenuated the increase of transaminases activities,bilirubin and creatinine rate,and improved catalase and superoxide dismutase activities,while reducing malondialdehyde contents in the liver and kidney.E.cordifolia extract significantly prevented histological damages observed in the malaria control group.No acute toxicity sign was observed in mice with plant extract at the dose up to 5000 mg/kg.Conclusions:E.cordifolia extract at 200 and 400 mg/kg showed significant antimalarial effects.This results support its traditional use in the treatment of malaria.

ATP gatekeeper of Plasmodium protein kinase may provide the opportunity to develop selective antimalarial drugs with multiple targets

Malaria is one of the most devastating infectious diseases that caused millions of clinical cases annually despite decades of prevention efforts. Recent cases of Plasmodium falciparum resistance against the only remaining class of effective antimalarial(artemisinin) in South East Asia may soon pose a significant threat. Hence, the identification of new antimalarial compounds with a novel mode of action is necessary to curb this problem. Protein kinase has been implicated as a valid target for drug development in diseases such as cancer and diabetes in humans. A similar approach is now recognized for the treatment of protozoan-related disease including malaria. Few Plasmodium protein kinases that are not only crucial for their survival but also have unique structural features have been identified as a potential target for drug development. In this review, studies on antimalarial drug development exploiting the size of Plasmodium protein kinase ATP gatekeeper over the past 15 years are mainly discussed. The ATP-binding site of Plasmodium protein kinases such as Pf CDPK1, Pf CDPK4, Pf PKG, Pf PK7, and Pf PI4K showed great potential for selective and multi-target inhibitions owing to their smaller or unique ATP-gatekeeper amino acid subunits compared to that of human protein kinase. Hence it is a feasible solution to identify a new class of active antimalarial agents with a novel mode of action and longer clinical life-span.

Pattern of Uncomplicated Malaria Treatment and Antimalarial Prescription Practices among Health Workers in the Littoral Region of Cameroon: An Assessment of Ten Years Post-Malaria Treatment Policy Change

Following highly prevalent Plasmodium resistant strains to antimalarial monotherapies in malaria endemic countries, uncomplicated malaria treatment policy changed to artemisinine-based combination therapies (ACTs). After adoption of this new treatment policy in a country, sufficient care is needed to be taken to prevent occurrence of resistance to the latest drugs. As Cameroon shifted to ACT in 2004, this study aimed to assess knowledge and practices of health workers in government health facilities of the Littoral region regarding mild malaria management in health facilities as well as according to prescription qualities of ACTs in leaflets received in pharmacies. A total of 66 physicians and 16 nurses were questioned in 10 health facilities and 503 medical leaflets with ACTs prescriptions were viewed in 17 pharmacies. All medical workers questioned correctly were defined mild malaria and were aware of the antimalarial policy change in Cameroon. Overall ACTs prescription for mild malaria management in children and adult patients was 72.2% and 87.8% respectively. An important proportion of health workers prescribed antimalarial monotherapies and non recommended antimalarial for uncomplicated malaria treatment. 31.7% of participants did not systematically recommend laboratory diagnostic test before antimalarial prescription. Of leaflets viewed in pharmacies, ACTs were prescribed by physicians, nurses and laboratory technicians. Age was the only criteria for ACTs prescription. Appropriate ACTs quality prescription ranged between 81.2% and 94.4%. Of the ACTs prescribed, blisters had the highest (92.9%) appropriate quality prescription and solutions the lowest (83.3%). According to qualification of prescribers, physicians had the highest score (93.1%) of appropriate quality prescription and laboratory technicians the lowest score (28.1%). For all ACTs containing medical leaflets, concomitant medications were recorded namely antipyretic (73.9%), antibiotic (21.9%), non steroid anti-inflammatory (19.9%) or vitamins (18.1%). Data gathered indicated that although health workers were aware of uncomplicated malaria treatment policy change in Cameroon, mild malaria mismanagement was prevailing in health facilities of the Littoral region and ACTs quality prescription in medical leaflets was not optimal. Therefore, awareness is still needed among prescribers in order to prevent or at least slow the occurrence of Plasmodium resistant strains to ACTs in Cameroon.

Comparison of Molecular Properties (Stabilities, Reactivity and Interaction) of Manzamenones and Two Antimalarial Drugs (Quinine and Artemisinin) Using Mixed Method Calculations (ONIOM) and DFT (B3LYP)

Malaria is a real public health problem. It’s one of the pathologies that mobilize the scientific community. Resistance to existing treatments is the basis for the search for new treatments. Some molecules such as Manzamenones have shown important antimalarial properties. These molecules belong to the family of atypical fatty acid derivatives. This work presents the relative stabilities, some reactivity properties and the privileged sites of interaction by hydrogen bond of fourteen Manzamenones and two antimalarial drugs: quinine and Artemisinin. These analyses were performed using quantum chemical calculations. We employed the two-layer ONIOM calculation method;namely ONIOM (B3LYP/6-311++G (d, p): AM1) for the fourteen Manzamenones. The geometries of the two antimalarials are calculated at B3LYP/6-311++G (d, p). The electrostatic potential (ESP) calculation of all molecules is done at the B3LYP/6-31++G (d, p) level. The formation processes of the molecules are discussed from the thermodynamic quantities we have calculated. The relative stabilities, the energies of the frontier orbitals, the energy gaps, the dipole moment, etc., are evaluated and discussed. The electrostatic potential at the molecular surface has been used to identify the sites favorable to the formation of hydrogen bonds.

Antimalarial activity of a novel series of artemisinin-derived 1, 2, 3-triazole dimers

Objective: To obtain suitable artimisinin-based drug candidates with high antimalarial activity.Methods: Three different reaction schemes were used to synthesize a total of 15 artemisininbased compounds.The first synthetic scheme involved the synthesis of diazido aliphatic and aromatic compounds from commercially available dihalides and azido derivatives of artemisinin.The second scheme consisted of the reaction of dibromoaliphatic compounds with sodium azide in dimethylformamide which yielded the desired compounds.Artemisinin-based compounds on treatment with sodium azide and bromotrimethylsilane in dichloromethane produced the most potent compound GB-2.Another potent compound GB-1 was synthesized from artemisinin by treatment with alcohols in the presence of Aberlyst-15 in anhydrous dichloromethane.The third scheme involved the Huisgen 1,3-dipolar cycloaddition between the synthesized aliphatic and aromatic diazides and two alkyne derivatives of artemisinin to obtain the desired artemisinin dimers with average yields.Results: The best in vitro antiplasmodial activity was shown by the compound GB-2 registering IC_(50) value 0.066 μg/mL against chloroquine-sensitive and 0.865 μg/mL against chloroquineresistant strains of Plasmodium falciparum.It suppressed 59.0% parasitaemia in vivo of rodent malaria parasite Plasmodium berghei in Swiss albino model at 50 μg/kg body weight dosage.Molecular docking interactions of Plasmodium falciparum ATP6(PfATP6) protein revealed strong bonding of GB-2 with Thr255 residue which is likely to be the reason for excellent antimalarial activity of this compound.Conclusion: Two compounds GB-1 and GB-2 exhibited excellent in vitro antiplasmodial activity and fair in vivo antimalarial activity.Of the two, GB-2 showed better activity which could be attributed to its strong bonding interactions with Thr255 as evidenced from the molecular docking study.Study helped in identifying artemisinin analogues possessing good antimalarial properties and further research in structural alterations of the selected molecules should be carried out which may result in obtaining potent drug candidates against the malarial parasite.

Antimalarial activities of butanol and ethylacetate fractions of Combretum nigricans leaf

Objective: To evaluate the antimalarial activity of the ethylacetate and butanol fractions of Combretum nigricans(C. nigricans) leaf extract in mice. Methods: C. nigricans solvent(butanol and ethylacetate) fractions were screened for their phytochemical constituents using standard procedures illustrated by Harborne and Evans. The Peters' 4-day suppressive test against early malaria infection, Rane's curative test against established malaria and prophylactic test for residual activity were employed for evaluating the antimalarial potential in mice. Results: The phytochemical screening revealed the presence of alkaloids, terpenoids, saponins, and flavonoids in both fractions at different intensity. Both fractions exhibited significant antimalarial activity in all test models(P<0.05). The ethylacetate fraction of C. nigricans had better chemosuppressive and curative effects compared to the butanol fraction, which however, elicited a better chemoprophylactic effect. The chemosuppressive effect of C. nigricans ethylacetate fraction(200-800 mg/kg) was 77.6%, 69.1% and 86.1%; curative effect was 62.3%, 71.3% and 72.4%; while the chemoprophylactic activity was 32.1%, 48.6% and 61.2% respectively. C. nigricans butanol fraction(200-800 mg/kg) had 40.3%, 54.1% and 69.1% chemosuppression; 26.2%, 36.9% and 34.5% curative effect; and 48.4%, 70.0% and 87.4% chemoprophylaxis. Conclusions: Both solvent fractions of C. nigricans possess antimalarial activity, and may be useful at different stages of malaria therapy.

Antimalarial activity of Ageratum conyzoides in combination with chloroquine and artesunate

Objective:To determine the suppressive and curative activity of aqueous leaf extract of Ageratum conyzoides(A.conyzoides) in combination with chloroquine and artesunate, respectively against Plasmodium berghei infection in mice.Methods:Using malaria(Plasmodium berghei) infected albino mice of both sexes,aqueous extracts of A.conyzoides in combination with chloroquine and artesunate were tested for antimalarial activity,respectively.Four-day suppressive test and Rane’s curative test were carried out.Results:Suppressive tests showed significant dose dependent reduction in parasitemia level produced by the extract-chloroquine and extract-artesunate combinations.Suppressive activities of both extract-drug combinations were greater than the individual drugs alone.Extract-chloroquine(100:5) produced the highest suppressive effect(98%suppression).Curative tests showed absolute survival in two extract-drug combinations.Two extract-drug combinations produced higher curative effects than the individual drugs alone.The highest dose combinations of extract-chloroquine(100:5) and extract-artesunate(100:5) produced absolute parasitemia clearance(cure) in the infected mice. Conclusions:The study indicated that aqueous extract of A.conyzoides had the ability to potentiate the antimalarial activity of chloroquine and artesunate against induced plasmodiasis in mice.It contributes a lot in the malaria endemic and poverty stricken tropics.

Computational Analysis of Physicochemical, Pharmacokinetic and Toxicological Properties of Deoxyhypusine Synthase Inhibitors with Antimalarial Activity

Malaria is a parasitic disease which has as etiological agents protozoa of the genus Plasmodium prevalent in tropical countries. The appearance of Plasmodium strains resistant to artemisinin has become necessary the development of new drugs using computational tools to combat this epidemic. Diverse transporter proteins can act as antimalarials targets, thereby being the enzyme deoxyhypusine synthase a promising antimalarial target. The present study aimed to investigate 15 most active inhibitors of deoxyhypusine synthase target, deposited in databases Binding DB, in order to trace a pattern of physicochemical, pharmacokinetic and toxicological properties of the inhibitors for this enzyme and propose new inhibitors of deoxyhypusine synthase target. The physicochemical properties were obtained according to the Lipinski parameters to evaluate oral absorption. Based on the certain properties were proposed three new inhibitors (A, B and C). The ADME/Tox properties were calculated for new inhibitors compared with results of the selected compounds. The fifteen inhibitors for oral administration showed satisfactory results, because they have adapted to the Lipinski parameters. In relation to the penetration of the blood-brain barrier the inhibitors analyzed showed penetration values less than 1, and ranged from 0.0411815 to 0.481764, being that the compound 1 showed value of CBrain/CBlood = 0.135467. Compound B showed a higher strength in plasma protein binding in relation to the compound 1, having a variation be-tween them of ±1.489344. Therefore, the compound B would present a longer halflife compared with compound 1. The proposed compounds showed positive and satisfactory results, being able to reach less adverse effects related to the central nervous system depending of administered dose.

Bioactive compounds fractionated from endophyte Streptomyces SUK 08 with promising ex-vivo antimalarial activity

Objective: To determine ex vivo antimalarial activity and cytotoxicity of endophytic Streptomyces SUK 08 as well as the main core structure fractionated from its crude extract.Methods: The activities of SUK 08 crude extract were evaluated by using the Plasmodium lactate dehydrogenase assay and synchronization test against rodent malaria parasite Plasmodium berghei, instead of human malarial parasite Plasmodium falciparum. The cytotoxicity of the crude extract was determined by MTT assay. The crude extract was analyzed by thin-layer chromatography and gas chromatography–mass spectrophotometry.Results: The ethyl acetate crude extract showed very promising antimalarial activity with IC50 of 1.25 mg/m L. The synchronization tests showed that ethyl acetate extraction could inhibit all stages of the Plasmodium life cycle, but it was most effective at the Plasmodium ring stage. On the basis of a MTT assay on Chang Liver cells, ethyl acetate and ethanol demonstrated IC50 values of >1.0 mg/m L. The IC50 of parasitemia at 5% and30% for this extract was lower than chloroquine. Thin-layer chromatography, with 1: 9 ratio of ethyl acetate: hexane, was used to isolate several distinct compounds. Based on gas chromatography–mass spectrophotometry analysis, three core structures were identified as cyclohexane, butyl propyl ester, and 2,3-heptanedione. Structurally, these compounds were similar to currently available antimalarial drugs.Conclusions: The results suggest that compounds isolated from Streptomyces SUK 08 are viable antimalarial drug candidates that require further investigations.

A New Antimalarial Noreudesmane Sesquiterpenoid from Dobinea delavayi

One previously undescribed angeloylated noreudesmane sesquiterpenoid,dobinin O(1),along with four known eudesmane sesquiterpenoids(2-5)were isolated from the peeled roots of Dobinea delavayi.Their structures were elucidated by extensive spectroscopic data analyses.In addition,compound 1 exhibited moderate antimalarial activity against Plasmodium yoelii BY265RFP with the inhibition ratio of 17.8±13.3%at the dose of 30 mg/kg/day.

Utilization of the current national antimalarial treatment guidelines among doctors in army hospitals in Lagos, Nigeria

Introduction: Human malaria infection remains a problem of public health importance in many regions of the world. The infection continues to spread particularly in sub-Saharan Africa. In Nigeria, malaria and its treatment have been affected by factors like wrong diagnosis, wrong attitude of the people, unavailability of drugs, fake and substandard drugs, attitude and practices of medical and paramedical personnel. Nigeria’s national standard for malaria treatment was recently changed to artemisinin combination therapy. Methods: A descriptive study using a structured questionnaire was administered to all doctors (123) practicing in the three Army hospitals in Lagos. The study was done between March, 2009 and April, 2009. The findings were precoded;data entry and analysis was done using EPI INFO version 3.5.1 statistical software. Results: Presumptive/clinical diagnosis was still a common practice for diagnosing malaria among doctors, as well as the use of microscopy. None of the doctors had the facility for diagnosing malaria with rapid diagnostic test in their hospitals. Fifty one percent of the doctors stated that they utilized the current National antimalarial treatment guidelines. Significant proportion of the doctors used Artemisinin-based Combination Therapy (ACTs) as first line treatment of uncomplicated malaria in adults and children. Chloroquine was the commonest drug for first line treatment of uncomplicated malaria in pregnancy. Only 45.5% of the doctors had correct knowledge of Intermittent Preventive Treatment in pregnancy (IPTp), while 33.3% knew the stage of pregnancy in which a pregnant woman should receive IPTp with sulphadoxine-pyrimethamine. Awareness and the content of knowledge of the current National antimalarial treatment guideline were not affected by the category or current position of the doctors. Thirteen percent of the respondents had attended training/update workshop organized by the Federal Ministry of Health (FMOH) Roll Back Malaria programme on the current National antimalarial treatment guideline. Conclusion: The study showed that there is need to improve use of recommended antimalarial medicines for all categories of patients by doctors in Army Hospitals in Lagos. More effort should be made by the Federal Ministry of Health and other stakeholders to organize training and refresher courses on the current National antimalarial treatment guidelines for all categories of health care providers.

Analytical Tools and Strategic Approach to Detect Poor Quality Medicines, Identify Unknown Components, and Timely Alerts for Appropriate Measures: Case Study of Antimalarial Medicines

Nowadays, the circulation of poor quality medicines is becoming an alarming worldwide phenomenon with serious public health and socio-economic concerns. The situation is particularly critical in developing countries where drug quality assurance and regulatory systems for drug manufacturing, importation, distribution and sales are weak. A sustained vigilance on poor quality medicines that regroup counterfeit/falsified, substandard and degraded medicines is therefore required to ensure patient safety and genuine medicines integrity. A case situation is illustrated including a strategic approach and analytical tools that were found useful to detect poor quality medicines, identify unknown components, and timely alerts for appropriate measures against the spread of those harmful products. Several suspected medicines randomly sampled in several strategic Rwandan areas were firstly check-controlled by means of visual inspection and then applying several analytical techniques from simple to more complex ones. The following medicines were studied: quinine sulfate tablets, artemisinin-based combination tablets, and artesunate powders for injection. Taking into account the pharmaceutical forms and the chemical characteristics, the following tests were applied: uniformity of mass, friability, disintegration, fluorescence, identification and assay. They were followed by more complex analytical techniques that allowed more comprehension of abnormal findings among which the presence of a wrong active pharmaceutical ingredient in quinine sulfate tablets which is mainly discussed in this paper to illustrate a strategic approach and various analytical tools that can be used in detecting and identifying unknown component in poor quality medicines.

Fighting Poor Quality Medicines: Development, Transfer and Validation of Generic HPLC Methods for Analyzing Two WHO Recommended Antimalarial Tablets

As serious but neglected public health problems, poor quality medicines, i.e. for antimalarial medicines, urged to be fought. One of the approaches is to consider the analytical chemistry and separative techniques. In this study, a generic liquid chromatographic method was firstly developed for the purpose of screening 8 antimalarial active ingredients, namely amodiaquine (AQ), piperaquine (PPQ), sulfalene (SL), pyrimethamine (PM), lumefantrine (LF), artesunate (AS), artemether (AM) and dihydroartemisinine (DHA) by applying DoE/DS optimization strategy. Since the method was not totally satisfying in terms of peak separation, further experiments were undergone applying the same development strategy while splitting the 8 ingredients into five groups. Excellent prediction was observed prior to correlation between retention times of predicted and observed separation conditions. Then, a successful geometric transfer was realized to reduce the analysis time focusing on the simultaneous quantification of two WHO’s recommended ACTs in anti-malarial fixed-dose combination (AM-LF and AS-AQ) in tablets. The optimal separation was achieved using an isocratic elution of methanol-ammonium formate buffer (pH 2.8;10 mM) (82.5:17.5, v/v) at 0.6 ml/min through a C18 column (100 mm × 3.5 mm, 3.5 μm) thermostated at 25℃. After a successful validation stage based on the total error approach, the method was applied to determine the content of AM/LF or AS/AQ in seven brands of antimalarial tablets currently marketed in West, Central and East Africa. Satisfying results were obtained compared to the claimed contents.