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- ItemOpen AccessThe antimicrobial activities of selected local medicinal herbs against Streptococcus pneumoniae(Kamuzu University of Health Sciences, 2021-07-01) Salifu Mindress, ChifundoStreptococcus pneumoniae (S. pnuemoniae) is a major cause of invasive pneumococcal infections. Current treatment involves antibiotic therapy and vaccination. The emergence of antibiotic resistance and vaccine serotype replacement negatively affects the control of pneumococcal infections, necessitating the need for other treatment alternatives. We investigated the antimicrobial activity of local herbs against pneumococcal serotypes 1 and 6A. Dry powdered leaves/stem material (50 g) from 6 plants; Annona senegalensis (A. senegalensis), Bidens pilosa (B. pilosa), Dichrostachys cinerea (D. cinerea), Erythrina abyssinica (E. abyssinica), Lippia javanica (L. javanica) and Trichodesma zeylenicum (T. zeylenicum)) were extracted using 200 mL of distilled water or methanol. Disc diffusion method was employed for antimicrobial activity testing. The minimum inhibitory concentrations (MIC’s) and minimum bactericidal concentrations (MBC’s) were determined using agar dilution method. Column chromatography was employed for fractionation of crude extracts. Penicillin and DMSO (1 % in DPBS) were used as positive and negative control, respectively. Water extraction yielded 5.1 % (10.2 g/200 g) of the crude extract material versus 12.1 % (24.3 g/200 g) from methanol. The Bp (1.0 mg/mL) and Ea (1.0 mg/mL) water extracts showed highest activity against serotype 1 (zone of inhibition (ZI) ~9.0 mm each), while Bp and Dc (ZI ~11.0 mm) exhibited the highest activity against serotype 6A. The methanol extracts of B. pilosa (1.0 mg/mL) and D. cinerea (1.0 mg/mL), showed the highest activity against serotype 1 (ZI ~15.6 ± 0.57, MIC<100 𝜇g/mL, MBC ~ 2 mg/mL and ZI ~13.6 ± 0.57 mm, 100 ≤ MIC <512 𝜇g/mL, MBC ~ 4 mg/mL respectively) and serotype 6A (ZI ~24.3 ± 0.00 mm, MIC <100 𝜇g/mL, MBC ~2 mg/mL and ZI ~15 ± 0.00 mm, 100 ≤ MIC<512 𝜇g/mL, MBC ~ 4 mg/mL respectively). The ZI for both serotypes 1 and 6A were 0.00 mm for DMSO (1 %) and 25 ± 0.00 mm for penicillin (25 μg). Column fractionation vi was conducted on methanol extracts of B. pilosa and D. cinerea. Of the 9 fractions from B. pilosa, only one fraction showed activity against serotypes 1 and 6A (ZI ~10 mm). Of 11 fractions from D. cinerea, only one showed activity against pneumococcal serotypes 1 (ZI ~8 mm) and 6A (ZI ~7 mm). Phytochemical analysis of methanol extracts showed higher content of total polyphenols, flavonoids, 2, 2-Diphenyl-1-Picrylhydrazyl (DDPH), Ferric Reducing Antioxidant Power (FRAP) and total alkaloids compared to water extracts. The Brine Shrimp’s lethality analysis for highly active plant (Bp and Dc) showed no and mild toxicity respectively. We recommend further exploration of these two plants as potential antimicrobials against pneumococcal infections.
- ItemOpen AccessAssessing antibiotic prescribing patterns and utilization of microbiological tests results for common bacterial infections in under five inpatients at Ntchisi District Hospital, Malawi(Kamuzu University of Health Sciences, 2021-04-01) Kondowe, DavieAntibiotics have remained useful to humans and animals in the treatment of serious infectious diseases for decades now. Unfortunately, irrational antibiotic use has resulted in the emergency of antimicrobial resistance. The aim of this study was to assess antibiotic prescribing patterns and utilization of microbiological test results in common bacterial infections, and enhance existing interventions for the improvement of rational antibiotic use. This was a hospital based study, designed as prospective cross-sectional, which was conducted at Ntchisi district hospital, Malawi. The study used a structured questionnaire which involved prospectively reviewing and recording information from files of under-five patients admitted in peaditric ward. Convenience sampling method was used to enroll participants in the study. The study enrolled 373 participants who were prescribed antibiotics. The outcomes of the study were to assess antibiotic prescribing patterns in under five inpatients, evaluate utilization of microbiological test results of common bacterial infection in under five patients and find out the correlation or association between antibiotic prescribing pattern and utilization of microbiological test results in under five inpatients. According to Malawi Standard Treatment Guidelines, among the 373 recruited participant 76.68 % were appropriately prescribed antibiotics and 23.32 % were inappropriately prescribed antibiotics (p=<0.001). The most prescribed antibiotics were a combination of Benzyl penicillin and gentamycin 276(74.0%), followed by ceftriaxone 87(23.2%) and metronidazole 10(2.7%) (p=<0.001), 318(85.25%) had antibiotic prescription without a request for microbiological test and only 55(14.75%) had antibiotic prescription with a requested microbiological test (p=<0.001). Among the 55(14.75%) cerebral spinal fluid (CSF) samples sent to the vii laboratory, 46/55 CSF samples were analyzed and all the samples had negative result. Culture and sensitivity was not performed because of lack of laboratory resources. There was no utilization of these microbiological test results to maintain, change or discontinue treatment by the prescribers. It was observed that antibiotic prescriptions were made empirically. The study found that the correlation between antibiotic prescribing pattern and utilization of microbiological test results was not statistically significant (p=0.288).
- ItemOpen AccessComparison of malaria parasite clearance times during quinine and artesunate administration for cerebral Malaria in Blantyre, Malaw(Kamuzu University of Health Sciences, 2021-07-01) Saidi, Alexuse MustaphMalaria which is caused by Plasmodium species is one of the most important human parasitic diseases. In recent years, preceding 2014, the most severe form of the disease, cerebral malaria, was recommended by World Health Organization (WHO) to be treated with quinine, but due to its increased side effects over the recently discovered drug, artemisinin derivatives, WHO substituted quinine as first line treatment with artemisinin derivatives in combination with a long-acting drug such as lumefantrine, piperaquine, amodiaquine, mefloquine, pyronaridine or sulfadoxine-pyrimethamine. Delay in parasite clearance time in treated patients is the main characteristic of parasite resistance to a particular antimalarial drug. Malaria parasites have already shown resistance to the currently recommended artemisinin derivatives in South East Asia, a development that prompted WHO to recommend periodic monitoring of the drug's effectiveness in endemic countries. Malawian children admitted with cerebral malaria (CM) between 2010 and 2019 in a long-standing pathogenesis study at Blantyre’s main referral hospital, Queen Elizabeth Central Hospital (QECH) were retrospectively sampled at admission and every six hours until two consecutive malaria smears were negative. This was done to monitor parasite clearance times across those years. Yearly average clearance time was compared to 2014, the year when artesunate replaced quinine as first-line therapy for CM in Malawian hospitals. Parasite clearance time was shown to be slower during the quinine era compared to the artesunate, an indication that artesunate is superior to quinine. There was no increase in clearance times from the onset of artesunate as first-line therapy, showing that the current recommended anti-malarial drug is still effective.
- ItemOpen AccessComparison of malaria parasite clearance times during Quinine and Artesunate administration for cerebral malaria in Blantyre, Malawi(Kamuzu University of Health Sciences, 2021-07-01) Saidi, Alexuse MustaphMalaria which is caused by Plasmodium species is one of the most important human parasitic diseases. In recent years, preceding 2014, the most severe form of the disease, cerebral malaria, was recommended by World Health Organization (WHO) to be treated with quinine, but due to its increased side effects over the recently discovered drug, artemisinin derivatives, WHO substituted quinine as first line treatment with artemisinin derivatives in combination with a long-acting drug such as lumefantrine, piperaquine, amodiaquine, mefloquine, pyronaridine or sulfadoxine-pyrimethamine. Delay in parasite clearance time in treated patients is the main characteristic of parasite resistance to a particular antimalarial drug. Malaria parasites have already shown resistance to the currently recommended artemisinin derivatives in South East Asia, a development that prompted WHO to recommend periodic monitoring of the drug's effectiveness in endemic countries. Malawian children admitted with cerebral malaria (CM) between 2010 and 2019 in a long-standing pathogenesis study at Blantyre’s main referral hospital, Queen Elizabeth Central Hospital (QECH) were retrospectively sampled at admission and every six hours until two consecutive malaria smears were negative. This was done to monitor parasite clearance times across those years. Yearly average clearance time was compared to 2014, the year when artesunate replaced quinine as first-line therapy for CM in Malawian hospitals. Parasite clearance time was shown to be slower during the quinine era compared to the artesunate, an indication that artesunate is superior to quinine. There was no increase in clearance times from the onset of artesunate as first-line therapy, showing that the current recommended anti-malarial drug is still effective.
- ItemOpen AccessDeterminants of decisions between clinician and patient to prescribe antimicrobials: A clinician’s perspective(Kamuzu University of Health Sciences, 2021-10-19) Chalusa, MorrisAntimicrobial resistance is a great public health challenge which has been accelerated by the inappropriate use of antimicrobials. The inappropriate use of antimicrobials is associated with the increased risks of prolonged hospital stay, self-medication of self-limiting conditions and more admissions to hospitals. Some of the factors that increase antimicrobial resistance appear to be modifiable and are determine by clinician-patient communication. Increased antimicrobial resistance was the cause of severe infections in the year 2012 in Malawi. Out of a total of 100,000 recorded deaths, 70,200 (70.1%) were attributable to infectious diseases. A qualitative study was used to find out what factors determine the decision between clinician and patient to prescribe antimicrobials when not necessitated in Mulanje, Malawi, through the use of unstructured questionnaires, semi-structured interviews and focus group discussions. Clinicians’ knowledge of antimicrobial resistance as well as their communication skills was also sought. Interview and open ended survey responses were translated, transcribed and coded for themes. Participants pointed out that patient preferences, patient belief and clinician lack of education were among the factors that contribute to the decisions to prescribe antimicrobials. Most clinicians showed lack of knowledge on the definition of antibiotic and antimicrobial resistance. Inappropriate use of antimicrobials is facilitated by prescribing decisions made by clinicians who are greatly influenced by their patients. Improving antimicrobial prescription requires educational interventions for both clinicians and patients.
- ItemOpen AccessDevelopment of Loop-mediated Isothermal Amplification (lamp) for detection of macrolide-resistant genes in Streptococcus Pneumoniae(Kamuzu University of Health Sciences, 2020-12-01) Msefula, JacqulineAntibiotic resistance is fast becoming a major health problem, which makes it difficult to treat several infections, including Streptococcus pneumoniae infection. Increasing access to antibiotics, presumptive treatment especially in low-resource settings, and self-medication are some of the factors contributing to the rise in antibiotic resistant pathogens. Therefore, a robust surveillance platform for emergence of drug-resistant pathogens is a public health imperative. Diagnostic tools that could help with early detection, monitoring of resistance patterns and determining the prevalence of pathogens and pathogen resistance are urgently needed. In this study we have addressed the latter need by developing a method for the detection of macrolide resistant Streptococcus pneumoniae using loop-mediated isothermal amplification (LAMP) assay. The LAMP assay has increased specificity and sensitivity with a reduced time frame of detection. Rational: There is a growing need to develop diagnostic tools in early detection of antimicrobial resistance and real time surveillance. We aimed to develop a LAMP method for the rapid detection of antimicrobial resistant S. pneumoniae that could help in monitoring macrolide resistance in resource limited areas. Methods: A laboratory method, development study was conducted to develop a LAMP assay for the detection of macrolide resistance genes in S. pneumoniae from Blantyre, Malawi. S. pneumoniae isolates were obtained from an on-going community-based pneumococcal carriage surveillance project. Nasopharyngeal swabs were collected from children below the age of five in urban Blantyre. Isolates’ resistance profiles including erythromycin and azithromycin resistance were determined using phenotypic methods at Malawi-Liverpool-Wellcome Trust (MLW) laboratories. Whole genome sequencing (WGS) was done at the University of Oxford, United Kingdom. LAMP primers for the detection of macrolide resistance genes mefA and ermB were designed from two sequenced S. pneumoniae isolates genomes using Premier Biosoft software. The cut-off for amplification and the sensitivity and specificity of the LAMP primers was determined using the Receiver operating characteristic curve (ROC) Antimicrobial resistance phenotyping on culture was used as the gold standard test. Resistance results turn-around time was calculated for both culture and the LAMP assay. Results: 79 S. pneumoniae isolates were analyzed on the LAMP assay and results were compared to conventional culture method. Primers designed to detect azithromycin, mefA had sensitivity = 97.1% and specificity = 100%, at 95% confidence interval 0.952 to 1.000; while for erythromycin, ermB had sensitivity = 97.1% and specificity = 95.8%, at 95% confidence interval 0.452 to 0.701. LAMP assay amplified both azithromycin and erythromycin resistance genes within 30 minutes of the run. Furthermore, detection time for both ermB and mefA primers including DNA isolation and LAMP assay took <3 hours versus the conventional culture methods antimicrobial sensitivity testing (AST) which ranges from 24 to 48 hours to generate results. Conclusion: The study successfully developed and evaluated the performance of the LAMP assay for mefA and ermB gene in S. pneumoniae isolates. LAMP assay sensitivity and specificity performance for detection of mefA was excellent being a classifier of 0.98 the area under the Receiver Operating Curve (ROC). While for ermB it was an average classier with 0.57 area under ROC when both compared to conventional AST methods. The turnaround time for LAMP assay from pure isolate was less than 3 hours including nucleic acid isolation and detection compared to culture AST, which ranges from 24 to 48 hours. The study developed LAMP assay that can be used in the detection of bacterial resistance and provide results in timely fashion. Further evaluation of performance of the LAMP assays is recommended.
- ItemOpen AccessHealthcare-associated urinary tract infection in the Surgery Department at Queen Elizabeth Central Hospital: Deciphering risk factors and antimicrobial resistance patterns of isolated bacteria(Kamuzu University of Health Sciences, 2021-12-01) Gabriel, Kambale BundukiIn this dissertation, I investigated the risk factors associated with healthcare-associated infections among patients admitted in surgical wards of the Surgery department of the Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi. A particular focus was on healthcare-associated urinary tract infection (UTI). This dissertation is a result of three studies. The first one was a systematic review and meta-analysis of uropathogenic Escherichia coli (UPEC) and specifically their antimicrobial resistance and virulence profiles. The second study was a point-prevalence survey on healthcare-associated infections (HAI) and antimicrobial use in the surgery department at QECH. The third study was a cross-sectional study investigating risk factors associated with UTI and catheter-associated UTI. In addition, the study determined the antimicrobial resistance patterns of isolated bacteria from urine samples from patient suspected with hospital-acquired UTI. From the systematic review and meta-analysis, 1,888 UPEC isolates were included in the analysis. High antimicrobial resistance rates were observed among the antibiotic class of tetracycline in 69.1% (498/721), followed by sulphonamides in 59.3% (1119/1888), quinolones in 49.4% (1956/3956), and beta-lactams in 36.9% (4410/11964). Meanwhile, virulence factors with highest prevalence were immune suppressors (54.1%) followed by adhesins (45.9%). The point prevalence of HAI was 11.4% (n=12/105) (95% CI: 6.0%-19.1%), including 4 surgical site infections, 4 urinary tract infections, 3 bloodstream infections and 1 bone/joint infection. We identified the following risk factors for HAI; length-of-stay between 8 and 14 days (OR=14.4, 95% CI: 1.65-124.7, p=0.0143), presence of indwelling urinary catheter (OR=8.3, 95% CI: 2.24-30.70, p=0.003) and the history of surgery in the vii past 30 days (OR=5.11, 95% CI: 1.46-17.83, p=0.011). 29/105 patients (27.6%) were prescribed antimicrobials, most commonly the 3rd-generation cephalosporin, ceftriaxone (n=15). The prevalence of confirmed HA-UTI was 53.1% (179/337, 95% CI: 47.8-58.4). The CAUTI was observed in 53.9% (28/52, 95% CI: 40.0-67.1). Risk factors associated with HA-UTI and CAUTI were the age of patients, patients who are not married, low educational level (none or primary school), prostatic diseases, patients presenting UTI symptoms, hospital length of stay (>7 days). The most frequent isolated bacteria from patient with confirmed HA-UTI were E. coli in 46.4% (83/179), Klebsiella spp in 11.7% (21/179), Citrobacter spp in 9.5% (17/179), S. aureus in 5.9% (16/179), Enterobacter spp in 5.5% (10/179), Acinetobacter spp in 5% (9/179), Pseudomonas spp in 3.4% (6/179) and Enterococcus spp in 2.8% (5/179). Other emerging bacteria with potential of causing wide ranges of infections were also observed. These included Raoultella spp in 2.2% (4/179), Kluyvera ascorbata in 1.7% (3/179), Morganella morganii in 0.6% (1/179) and Proteus vulgaris in 0.6% (1/179). Resistance rates observed were 2.3% for carbapenems (meropenem and imipenem) (4/171 for each), 10.5% (18/171) for amikacin, 21.6% (36/167) for fosfomycin, 36.0% (58/161) for chloramphenicol, 50.1% (84/165) for nitrofurantoin, 53.9% (69/128) for amoxicillin-clavulanate and 54.0% (95/176) for ciprofloxacin. Healthcare-associated infections constitute a relatively high burden in the surgical ward of QECH. Reinforcing infection prevention and control measures will help in reducing their prevalence and hence reduce antimicrobial resistance. Empiric antibiotic therapy for UTI in the Surgery Department should be revised based on the antimicrobial resistance patterns of isolated bacteria.
- ItemOpen AccessInvestigation of antimycobacterial and antiviral activities of extracts and compounds isolated from Malawian medicinal plants(Kamuzu University of Health Sciences, 2020-11-01) Ngonda, Frank Billy BestonInfectious diseases accounts for approximately one-half of all the deaths that occurs in tropical countries including Malawi. Some of these infectious diseases are caused by microorganism such as mycobacteria and viruses. However, the threat of antimicrobial resistance is growing at an alarming rate and the situation has been aggravated in these developing countries due to so many factors including presence of multidrug resistants’ strains and over prescriptions. Therefore, the purpose of present study was to investigate the phytochemical constitutes and compounds isolated from Aeschynomene nyassana, Euphorbia whyteana, Euphorbia cooperi, Flueggea. virosa, Phyllanthus amarus, Ericae milanjiana and Rhus acuminatissima medicinal plants, determine their antimicrobial activities and cytotoxic properties. Ethnobotanical survey was conducted and several methods were used to identify and confirm the selections of plants understudy. Search engine on several online databases (Google Scholar, PubMed, MEDLINE, Scopus, Cochrane Library, and Science Direct) were used to identify medicinal plants with antiviral and antimycobacterial activities. The plants found were then matched with published and unpublished ethnobotanical survey data and database on the Flora of Malawi, Chewa Medical Botany by Brian Morris, Useful Plants of Nyasaland by Jessie Williamson and other sources. Seven plants, were identified for this research and these were extracted twice with solvents such as methanol, ethyl acetated and dichloromethane. Part of the methanol/water extracts obtained were subjected to alkaloid extraction scheme while the other part was subjected to column chromatograph. 1,3,6 – tri(3,4,5-trihydroxyphenyl) acetyl ester - β-Dglucopyranose, 1,2,3,4,6 – penta(3,4,5-trihydroxyphenyl) acetyl ester - β-D- glucopyranose, 1,2,3,6 – tetra(3,4,5-trihydroxyphenyl) acetyl ester - β-D- glucopyranose, 2,3,6 – tri(3,4,5- trihydroxyphenyl) acetyl ester - β-D- glucopyranose, compounds were obtained from Hexane: Ethyl acetate 50%; 80%; 90% and Ethyl acetate: Methanol 5% and the compounds were identified from the NMR spectra while Betulinic acid was obtained as a white amorphous powder, soluble in methanol, having been eluted with methylene chloride: methanol 9:1 from the silica gel column. The NMR spectral data was compared in reference literature and showed to be very similar to those of Betulinic acid compound. Benzoxylanthaquinone was identified by direct comparison of the spectroscopic data with those published literatures. The compound, Cyclanoline, greyish in colour was obtained from alkaloid extraction scheme and identified by direct comparison of the spectroscopic data with those published literatures. Mass spectra(ESIMS) were obtained with a Thermo-Finningan LCD DECA mass spectrometer and HRESIMS spectra were measured with a FTHRMS-Orbitrap (Thermo-Finnigan) mass spectrometer. The compound E5 m/z 695.33, yellowish in colour was obtained from alkaloid extraction scheme and identified by direct comparison of the spectroscopic data with those published literatures. Mass spectra(ESI-MS) were obtained with a Thermo-Finningan LCD DECA mass spectrometer and HRESIMS spectra were measured with a FTHRMS-Orbitrap (Thermo- Finnigan) mass spectrometer. The resultant crude extracts, fractions and compounds were used in the phytochemical screening and antimicrobial analysis. The phytochemical analysis involved spectrophotometric screening for pro/antioxidant properties of the crude extracts, fractions and compounds using HPTLC, DPPH, FRAP, Reducing power, Crocin bleaching assay, Cupric reducing antioxidant capacity and Nitric oxide radical scavenging activities. Cell viability and cytotoxicity studies were conducted using the Trypan blue dye exclusion, (3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT and Mammalian macrophage cytotoxicity assays while heavy metals analysing was performed using atomic absorption spectrometry. The antimycobacterial activities of crude extracts, fractions and compounds were assessed using microplate alamar blue assay. Compounds obtained were further assessed for drug susceptibility against resistant Mycobacterium tuberculosis using the BACTEC™ MGIT 320 system. The results of the review study identified 50 different families of medicinal plants comprising 90 plants species that are frequently used by traditional healers to treat various diseases in Malawi such as sexually transmitted infections, diarrhoea/dysentery, skin infections/rash, respiratory infection, cold/cough, fever, tuberculosis and herpes zoster. Furthermore, these medicinal plants also demonstrated some anti-viral and antimycobacterial activities. The compounds/compound groups identified in this study were categorized into eight distinct groups of flavonoids, alkaloids, saponins, phenolics, lignins, xanthones, proteins and peptide. In phytochemical analysis, results of crude extracts, fractions and compounds showed moderate DPPH scavenging activity, a dose dependent decrease in NO scavenging activity except for R. acuminatissinia while A. nyassana revealed reducing power ability that was significantly greater than standard Ascorbic acid. In HPTLC analysis, DPPH active spots showed pale-yellow coloured spots for the 4 plants understudy while the phenolic active blue colour spots were observed to be more visible on R. acuminatissinia and E. milanjiana. In PBMC viability analysis, the lymphocytes treated with Rhus acuminatissima and Ericae milanjiana had the lowest cell percent viability. The plants understudy also demonstrated a decrease in percent viability with increased time for all the plants extracts except for E. milanjiana and A. nyassana which showed some stimulative effects. A. nyassana and Euphorbia whyteana demonstrated relatively high cytotoxicity as compared to E. milanjiana, R. acuminatissima and standard drug, Doxorubicin. In heavy metal analysis, all the plants understudy displayed the least levels of toxic metals concentration in the order of Cadmium˂Chromium˂Lead. In the antimycobacterial analysis, F. virosa and E. milanjiana crude extracts displayed Minimum Inhibitory Concentration of 128 ug/ml and 512 ug/ml respectively while A. nyassana ANX fraction showed MIC of 256 ug/ml for M. smegmatis. E. cooperi, E. milanjiana and E. whyteana crude extracts displayed MIC value of 512 ug/ml while E. whyteana W1 fraction had MIC value of 252 ug/ml for M. ulcerans. The selectivity index (SI) values of plants understudy ranged from <0.082 – 2.20 and considerably good SI were observed in F. virosa, E. whyteana crude extracts and E. whyteana W1 fraction at 2.20, 0.625 viii and 0.985 respectively. In synergistic antimycobacterial analysis, the synergistic drug action showed Betulinic acid (EM8), 1,2,3,6 – tetra(3,4,5-trihydroxyphenyl) acetyl ester - β-Dglucopyranose (FV8) and Cyclanoline (C5) exhibited synergistic antimycobacterial activity at a final concentration of 18 ug/ml. The good synergistic results (susceptibility) were observed in combined EM8+INH and FV8+INH while a moderate synergistic result was observed in C5+INH indicating an additive effect of the combination. However, antagonistic activity (resistance) was observed in combined EM9+ETH and E1+ETH. Therefore, it can be concluded from the results that all the plants understudy showed considerable antimycobacterial activities against M. tuberculosis, M. ulcerans and M. smegmatis. The compounds obtained from the plants understudy also demonstrated synergistic properties with the first-line tuberculosis drugs, rifampicin; isoniazid ethambutol and streptomycin. Consequently, this study recommends that further studies to be undertaken in order to determine the mechanism of action of the novel compounds in order to unravel its exact potential to inhibit several pathogenic microbes especially resistant M. tuberculosis and M. ulcerans and also to evaluate whether its true pharmacological activities exist. Currently, an all-oral and less toxic treatment regimen of Buruli ulcer is been sought after and encouraged by WHO.
- ItemOpen AccessPhytochemical, antioxidant activity and toxicity evaluation of medicinal plants commonly used for asthma management in Malawi(Kamuzu University of Health Sciences, 2021-12-01) Mwambyale, TuntufyeAsthma is a chronic disease characterized by recurrent attacks of breathlessness and wheezing, which vary in severity and frequency from person to person. There is minimal scientific research on the efficacy, doses, toxicity and safety of herbal remedies used in the management of asthma in many countries including Malawi. Therefore, this study determined the brief chemical composition and toxicity and/or safety of herbal extracts from the medicinal plants that are commonly used to manage asthma in Malawi. This was achieved through qualitative and quantitative assessment of flavonoids and phenolics, screening for antioxidant activity using 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) assay and Ferric reducing antioxidant power assay (FRAP) as well as validated in vitro and in vivo acute toxicity test on Wistar rats of ethanolic herbal extracts of Erythrina abbysinica Lam. ex DC., Paederia bojeriana (A.Rich. ex DC.) Drake and Trichodesma zeylanicum (Burm.f.) R. Br. The results showed that Trichodesma zeylanicum (Burm.f.) R. Br, Paederia bojeriana (A.Rich. ex DC.) Drake and Erythrina abbysinica (Lam. ex DC) contained flavonoids and phenols. Highest total flavonoid content was found in E. abyssinica (Lam. ex DC.), (806.12±0.01 QE/mg). Highest total phenolic content was also found in E. abyssinica (Lam. ex DC.) (98.48±0.08 mg GAE/g). Antioxidant activity using DPPH % inhibition was highest in E. abyssinica (Lam. ex DC.) (86.59%) while FRAP results were highest in T. zeylanicum (Burm.f.) R. Br (21.85mg TAEC/g). In vitro toxicity showed that ethanolic root extract of P. bojeriana (A.Rich. ex DC.) Drake had the lowest LC50 values (LC50 = 11.09μg/ml) however, in vivo toxicity studies showed LC50 of 2000mg/kg in all extracts. This study has revealed that the ethanolic extracts of all extracts are rich in phytochemicals and antioxidant activities that are indicative of asthmatic activity in human beings according to the literature. The study has also shown that the plants are toxic in vitro but non-toxic in vitro.
- ItemOpen AccessStructure-based in silico identification of novel anticancer natural compounds for enhanced breast cancer chemotherapy(Kamuzu University of Health Sciences, 2022-01-01) Bvunzawabaya, Jonathan TatendaBreast cancer remains a serious public health concern all over the world with heavier burdens on developing countries. In Sub-Saharan Africa, the mortality rate for breast cancer is currently on the rise because of late diagnosis and poor treatment. Currently available chemotherapeutic drugs for breast cancer are associated with severe side effects and are now facing multi-drug resistance. Therefore, identifying new anti-cancer drugs by using structural information of potential drug targets such as the gamma secretase will enhance the fight against breast cancer. The objective of this study was to identify and characterize drug-like natural anti-breast cancer compounds from selected African natural products databases using structure-based virtual screening and chemoinformatic approaches. Exactly11304 compounds from four databases (Afrodb, NANPDB, Afrocancer, and ConmedNP) were curated and filtered to remove structural alerts and compounds that violate drug-like rules according to Lipinski and Veber, using KNIME analytics. The resulting druglikeNP dataset (437 compounds) had its, chemical space, scaffold diversity, and complexity analyzed using scaled Shannon entropy and cyclic system retrieval curves (CSR). The 437 compounds were docked into the binding site of gamma-secretase enzyme and the pharmacokinetic properties of the hit compounds were profiled using the pkCSM server. 60% of the compounds in the druglikeNP dataset contained lead-like physicochemical properties and occupied the same space as FDA-approved drugs. The scaffold diversity of druglikeNP was observed to be higher than that of FDA drugs based on Shannon entropy and CSR. Docking studies identified 12 compounds as potential inhibitors of the gamma-secretase enzyme (with binding energies ranging between -7.6 and -8.8 KCal/mol). In silico ADMET predictions revealed a majority of the 12 hit compounds have good pharmacokinetic and toxicity profiles. In this study drug-like natural compounds of African origin with potential inhibitory properties against a validated breast cancer target; gamma secretase enzymes were computationally identified. This work could be valuable to the ongoing efforts to discovery novel drugs for enhanced breast chemotherapy.