Utilization of Malaria Diagnostic Tests and Receipt of Anti-Malarial Drugs by Febrile Patients Attending Outpatient Clinics of Health Centre IV Facilities in Mukono District, Uganda

Background: Failure to demonstrate the presence of malaria parasites prior to treatment with anti-malarial drugs remains a challenge in Uganda, often resulting into over-prescription of anti-malarial drugs to febrile patients suspected of malaria. The aim of this study was to describe the role of utilization of malaria diagnostic tests and associated factors in the receipt of anti-malarial drugs among febrile patients suspected of malaria. Methods: In a cross-sectional study design, client-exit interviews with febrile patients and key-informant interviews with purposively selected health workers were conducted at outpatient clinics of health centre IV facilities in Mukono district. Data entry and analysis were done using EpiData 3.2 and STATA 10 respectively. Data were described using frequency distributions and proportions. Chi square was used in two by two tables, odds ratios as the measure of association and an alpha level of 0.05 was used in all significance tests. Results: Out of 408 respondents, the majority were female (252, 61.8%) and a third of the samples were aged five years and below. The mean age in years was 3.3 with a standard deviation of 2.1. More than half of the respondents (359, 88%) utilized malaria diagnostic tests and about half (241, 59%) received anti-malarial drugs. There were no statistically significant differences between utilizers and non-utilizers in most characteristics except age, history of indoor residual spraying and perceived satisfaction with services at outpatient clinics. Utilizers were 75% less likely to receive anti-malarial drugs than non-utilizers after controlling for age, sex and residence (OR: 0.25, 95%CI: 0.09, 0.66). Frequent power cut-offs as well as limited knowledge on malaria treatment guidelines amongst laboratory personnel were some of the major limitations to microscopic diagnosis of malaria. Conclusion: Utilizers were 75% less likely to receive anti-malarial drugs as opposed to non-utilizers. This implies that increasing utilization of malaria diagnostic tests can reduce the problem of over-prescription of anti-malarial drugs by 75% among those tested for malaria, since anti-malarial drugs would be received by only those with a parasi- tologically-confirmed diagnosis of malaria. Policy implications: To overcome the problem of over-prescription of anti-malarial drugs, there must be a policy that ensures a consistent power supply in all public health laboratories. Training of health workers should encompass all cadres and work-shifts for laboratory personnel should be established to enhance utilization of malaria diagnostic tests especially at night.

Anti-Malarial Targeting and Dosing Practices among Health Workers at Lower Level Health Facilities in Uganda

Background: Health worker shortages remain a significant challenge to delivery of health care services globally. Moving tasks, where appropriate, to less specialized health workers is recommended by the World Health Organization as a strategy to address this challenge. However, this concept is feared to raise specific quality concerns. This research aimed at assessing the performance of health workers to correctly prescribe (target) appropriate antimalarial treatment. Methods: We conducted a cross sectional study at three public health centre IVs in Uganda, with varying malaria transmission intensities (Kihihi-low, Kasambya-medium and Nagongera-high). We categorized prescribers into two groups: specialized prescribers (doctors and clinical officers) and less specialized prescribers (nurses and midwives). At each site, 100 records of patients seen between September and November 2011 and prescribed an antimalarial were retrieved for each group of prescribers. Correctness of the antimalarial drug prescribed and dose given were assessed for each group and compared to the 2005 Uganda national malaria treatment guidelines which recommend Artemether Lumefantrine (AL) for treatment of uncomplicated malaria and Quinine for complicated malaria. Results: Findings of the study showed that specialized health workers were more likely to target correctly as compared to the less specialized health workers [OR = 1.49 (1.00 - 2.22), p = 0.046]. Appropriateness of dosing was higher among specialized prescribers compared to less specialized prescribers however this was not significant [OR = 1.58 (0.77 - 3.25), p = 0.206]. Age of the participants, history of fever, diagnosis of malaria and prescription experience were not associated with correct targeting. Conclusion: This study shows that task shifting at the targeting level is not suitable;however, there is inadequate evidence to show that this also applies to anti-malarial dosing. Task shifting for the treatment of Malaria in Uganda should be investigated further using larger studies if it is to be considered as an option for solving the health worker shortages especially in regions with few specialized health workers but high malaria burden.

In Silico Evaluation of Anti-Malarial Agents from Hoslundia opposita as Inhibitors of Plasmodium falciparum Lactate Dehydrogenase (PfLDH) Enzyme

Malaria has continued to be a health and economic problem in Africa and the world at large. Many anti-malarial drugs have been rendered ineffective due to the emergence of resistant strains of Plamodium falciparum. A key malaria parasite enzyme in glycolytic pathway, P. falciparum lactate dehydrogenase (PfLDH) is specially targeted for anti-malarial drugs development. Thus, the aim of this investigation was to determine the in silico inhibition effects of antimalarial compounds from Hoslundia opposita Vahl. namely hoslundin, hoslundal and hoslunddiol on PfLDH enzyme. The compounds were docked to the three-dimensional structure of PfLDH as enzyme using AutoDock Vina in PyRx virtual screening software. Binding affinity and position of the inhibitors were evaluated using PyMol software. The PfLDH enzyme showed two binding sites: the cofactors binding site (Site A) and secondary binding site (Site B). In the absence of the cofactor all ligands showed higher affinity than NADH, and were bound to the cofactors binding site (Site A). When docked in the presence of the cofactor, site B was the preferred binding site. Binding to cofactor site with higher binding energy than NADH suggests that these ligands could act as preferential competitive inhibitors of PfLDH. However, the binding to site B also suggests that they may be non-competitive allosteric inhibitors. Amino acid residues Gly99, Asn140, Phe100 and Thr97 were indicated to form hydrogen bonds with Hoslundin. Hoslunddiol showed hydrogen bonding with Thr97 and Met30, while Hoslundal formed hydrogen bond with Thr101 and Asn140.

COVID-19 Coronavirus: Is Infection along with <i>Mycoplasma</i>or Other Bacteria Linked to Progression to a Lethal Outcome?

Most patients with COVID-19 disease caused by the SARS-CoV-2 virus recover from this infection, but a significant fraction progress to a fatal outcome. As with some other RNA viruses, co-infection or activation of latent bacterial infections along with pre-existing health conditions in COVID-19 disease may be important in determining a fatal disease course. Mycoplasma spp. (M. pneumonaie, M. fermentans, etc.) have been routinely found as co-infections in a wide number of clinical conditions, and in some cases this has progressed to a fatal disease. Although preliminary, Mycoplasma pneumoniae has been identified in COVID-19 disease, and the severity of some signs and symptoms in progressive COVID-19 patients could be due, in part, to Mycoplasma or other bacterial infections. Moreover, the presence of pathogenic Mycoplasma species or other pathogenic bacteria in COVID-19 disease may confer a perfect storm of cytokine and hemodynamic dysfunction, autoimmune activation, mitochondrial dysfunction and other complications that together cannot be easily corrected in patients with pre-existing health conditions. The positive responses of only some COVID-19 patients to antibiotic and anti-malaria therapy could have been the result of suppression of Mycoplasma species and other bacterial co-infections in subsets of patients. Thus it may be useful to use molecular tests to determine the presence of pathogenic Mycoplasma species and other pathogenic bacteria that are commonly found in atypical pneumonia in all hospitalized COVID-19 patients, and when positive results are obtained, these patients should treated accordingly in order to improve clinical responses and patient outcomes.

Supercritical carbon dioxide extraction of Triognella foenum graecum Linn seeds:Determination of bioactive compounds and pharmacological analysis

Objective: To investigate the effect of temperature and pressure on supercritical CO_2 extraction of Triognella foenum graecum Linn seeds, to determine the optimal condition which leads to highest percentage of the accumulative yield and revealing the chemical composition of supercritical CO_2 extract.Methods: Temperatures in the range of 40–60C and pressures in the range of 10–25 MPa were used. FTIR and GC–MS analysis were used to detect the bioactive compounds present in the extract. The broth dilution method and slope method were used to evaluate the anti-microbial and anti-tuberculosis activities and the in vitro anti-malarial assay was carried out according to the micro assay protocol of Rieckmann and his coworkers.Results: The temperature was more affected than the pressure on the extraction performance and the highest yield of the extract(3.111%) was attained at 60C and 10 MPa.FTIR and GC–MS showed that the chemical composition of the extract included conjugated linoleic acid methyl ester as the major active principle(with concentration of72.28%), followed by saturated fatty acid methyl esters(16.03%), steroids(8.09%) and organic siloxane compound(3.61%). The extract showed moderate anti-bacterial activity with MIC values 100, 250, 125 mg/m L towards Escherichia coli, Staphylococcus aureus and Streptococcus pyogenus respectively. It exhibited high inhibition effect towards the fungi Candida albican with MFC value(250 mg/m L). The extract had low antituberculosis activity with MIC value(100 mg/m L) and comparable MIC value(0.29 mg/m L) towards Plasmodium flaciparum.Conclusions: Supercritical CO_2 extraction as alternate and green technology is performed successfully to extract the bioactive compounds from the seeds of T. foenum graecum Linn and it is concluded that this extract can be used as an alternate source of synthetic anti-biotic drugs.

Self-Medication Practice against Malaria and Associated Factors in the City of Parakou in Northern Benin: Results of a Population Survey in 2017

Introduction: Self-medication is a common practice in Benin. It has many consequences on people’s health in general and develops chemoresistance in particular. Aim: The aim of this work is to study the practice of anti-malarial self-medication in the city of Parakou and to identify the associated factors with this practice. Methods: This was a descriptive cross-sectional analytical survey that took place in the period from April 15 to June 24, 2017. Adults who reported having had malaria symptoms in the last 6 months before the survey and living in 9 neighbourhoods randomly selected in the city of Parakou were included. A structured questionnaire collected their self-medication habit, the drugs used, the supply places and the reasons for this practice. Data were analysed using the Epi-data 3.1 software. Results: Of the 335 respondents included in this study, 141 (42.09%) had self-medicated including 130 (38.81%) with anti-malarial drugs. Fever is the main symptom of malaria cited by respondents (129% or 38.51%) followed by headache (93% or 27.76%). The most commonly used anti-malarial drugs for self-medication are quinine (60% or 44.45%) followed by artemisinin-based combination therapy (46% or 34.07%). Eighty-seven respondents (66.92%) did not have a good knowledge of the drug dosage. Reasons for self-medication were mainly the high cost of consultation fees (99% or 54.10%) and good knowledge of one’s illness (53% or 28.96%). Self-medication associated factors were fever (p = 0.04), non-prescription drugs supply in pharmacies (p Conclusion: Self-medication is a common practice in the city of Parakou. Medicines purchased without prescription in pharmacies and drugs availability in street facilitate this practice, which may compromise the effectiveness of anti-malarial drugs.

Binding Study of Cis-Atovaquone with Cytochrome bc1 of Yeast

Tans-Atovaquone is widely used as an effective drug to treat uncomplicated malaria. But its cis-isomer is not a drug. In the present study, we report energy minimized binding pattern of trans-Atovaquone and its cisisomer with cytochrome bc1 (cytbc1) of yeast. The new feature of this molecular docking computation is that structural parameters of the drug molecules have been determined from their crystal structures. The energy minimized structures of protein-drug complexes show that H-bond distant between His-181 of cytochrome bc1 and C=O of Atovaquone for trans-Atovaquone is 2.85 &Aring and 5.3 &Aring with the cis-isomer. The role of this H-bonding interaction in dictating drug potency is in conformity with proton-coupled electron transport mechanism of drug action.

Total Syntheses of Favolasins A,E,G and K,Polyketides Isolated from Cultures of the Basidiomycetes Fungi Favolaschia sp.BCC 18686 and Favolaschia calocera BCC 36684

The structures assigned to all four members,1-4,of the recently reported favolasin class of natural product have been prepared for the first time by chemical synthesis.Suzuki-Miyaura cross-coupling chemistry was used to establish the associated biaryl substructures.The key step used in preparing the 1,5-benzodioxepin ring system associated with compounds 3 and 4 was the acid-catalyzed 7-exo-tet cyclization of an appropriately substituted 2-(oxiran-2-ylmethoxy)phenol while a base-promoted 6-exo-tet cyclization of the same substrate was used to construct the 2,3-dihydrobenzo[b][1,4]dioxine core of target 2.The spectral data derived from the four synthetically-produced favolasins matched those reported for the corresponding natural products.Preliminary biological screening of compounds 1-3 as well as a suite of fourteen precursors reveal that they display no notable anti-bacterial,anti-fungal or anti-tumor activities but congener K(4)is active,in the mM range,against Plasmodium falciparum.

Bioactive metabolites from macrofungi: ethnopharmacology, biological activities and chemistry

Exploration of natural sources for novel bioactive compounds has been an emerging field of medicine over the past decades,providing drugs or lead compounds of considerable therapeutic potential.This research has provided exciting evidence on the isolation of microbe-derived metabolites having prospective biological activities.Mushrooms have been valued as traditional sources of natural bioactive compounds for many centuries and have been targeted as promising therapeutic agents.Many novel biologically active compounds have been reported as a result of research on medicinal mushrooms.In this review,we compile the information on bioactive structure-elucidated metabolites from macrofungi discovered over the last decade and highlight their unique chemical diversity and potential benefits to novel drug discovery.The main emphasis is on their anti-Alzheimer,antidiabetic,anti-malarial,anti-microbial,anti-oxidant,antitumor,anti-viral and hypocholesterolemic activities which are important medicinal targets in terms of drug discovery today.Moreover,the reader’s attention is brought to focus on mushroom products and food supplements available in the market with claimed biological activities and potential human health benefits.