Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-12 (of 12 Records) |
Query Trace: Fernandez FM[original query] |
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Prevalence of substandard and falsified artemisinin-based combination antimalarial medicines on Bioko Island, Equatorial Guinea
Kaur H , Allan EL , Mamadu I , Hall Z , Green MD , Swamidos I , Dwivedi P , Culzoni MJ , Fernandez FM , Garcia G , Hergott D , Monti F . BMJ Glob Health 2017 2 (4) e000409 INTRODUCTION: Poor-quality artemisinin-containing antimalarials (ACAs), including falsified and substandard formulations, pose serious health concerns in malaria endemic countries. They can harm patients, contribute to the rise in drug resistance and increase the public's mistrust of health systems. Systematic assessment of drug quality is needed to gain knowledge on the prevalence of the problem, to provide Ministries of Health with evidence on which local regulators can take action. METHODS: We used three sampling approaches to purchase 677 ACAs from 278 outlets on Bioko Island, Equatorial Guinea as follows: convenience survey using mystery client (n=16 outlets, 31 samples), full island-wide survey using mystery client (n=174 outlets, 368 samples) and randomised survey using an overt sampling approach (n=88 outlets, 278 samples). The stated active pharmaceutical ingredients (SAPIs) were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. RESULTS: Content analysis showed 91.0% of ACAs were of acceptable quality, 1.6% were substandard and 7.4% falsified. No degraded medicines were detected. The prevalence of medicines without the SAPIs was higher for ACAs purchased in the convenience survey compared with the estimates obtained using the full island-wide survey-mystery client and randomised-overt sampling approaches. Comparable results were obtained for full island survey-mystery client and randomised overt. However, the availability of purchased artesunate monotherapies differed substantially according to the sampling approach used (convenience, 45.2%; full island-wide survey-mystery client, 32.6%; random-overt sampling approach, 21.9%). Of concern is that 37.1% (n=62) of these were falsified. CONCLUSION: Falsified ACAs were found on Bioko Island, with the prevalence ranging between 6.1% and 16.1%, depending on the sampling method used. These findings underscore the vital need for national authorities to track the scale of ineffective medicines that jeopardise treatment of life-threatening diseases and value of a representative sampling approach to obtain/measure the true prevalence of poor-quality medicines. |
Electrothermal vaporization sample introduction for spaceflight water quality monitoring via gas chromatography-differential mobility spectrometry
Wallace WT , Gazda DB , Limero TF , Minton JM , Macatangay AV , Dwivedi P , Fernandez FM . Anal Chem 2015 87 (12) 5981-8 In the history of manned spaceflight, environmental monitoring has relied heavily on archival sampling. However, with the construction of the International Space Station (ISS) and the subsequent extension in mission duration up to one year, an enhanced, real-time method for environmental monitoring is necessary. The station air is currently monitored for trace volatile organic compounds (VOCs) using gas chromatography-differential mobility spectrometry (GC-DMS) via the Air Quality Monitor (AQM), while water is analyzed to measure total organic carbon and biocide concentrations using the Total Organic Carbon Analyzer (TOCA) and the Colorimetric Water Quality Monitoring Kit (CWQMK), respectively. As mission scenarios extend beyond low Earth orbit, a convergence in analytical instrumentation to analyze both air and water samples is highly desirable. Since the AQM currently provides quantitative, compound-specific information for air samples and many of the targets in air are also common to water, this platform is a logical starting point for developing a multimatrix monitor. Here, we report on the interfacing of an electrothermal vaporization (ETV) sample introduction unit with a ground-based AQM for monitoring target analytes in water. The results show that each of the compounds tested from water have similar GC-DMS parameters as the compounds tested in air. Moreover, the ETV enabled AQM detection of dimethlsilanediol (DMSD), a compound whose analysis had proven challenging using other sample introduction methods. Analysis of authentic ISS water samples using the ETV-AQM showed that DMSD could be successfully quantified, while the concentrations obtained for the other compounds also agreed well with laboratory results. |
Quality of artemisinin-based combination formulations for malaria treatment: prevalence and risk factors for poor quality medicines in public facilities and private sector drug outlets in Enugu, Nigeria
Kaur H , Allan EL , Mamadu I , Hall Z , Ibe O , El Sherbiny M , Wyk AV , Yeung S , Swamidoss I , Green MD , Dwivedi P , Culzoni MJ , Clarke S , Schellenberg D , Fernandez FM , Onwujekwe O . PLoS One 2015 10 (5) e0125577 BACKGROUND: Artemisinin-based combination therapies are recommended by the World Health Organisation (WHO) as first-line treatment for Plasmodium falciparum malaria, yet medication must be of good quality for efficacious treatment. A recent meta-analysis reported 35% (796/2,296) of antimalarial drug samples from 21 Sub-Saharan African countries, purchased from outlets predominantly using convenience sampling, failed chemical content analysis. We used three sampling strategies to purchase artemisinin-containing antimalarials (ACAs) in Enugu metropolis, Nigeria, and compared the resulting quality estimates. METHODS: ACAs were purchased using three sampling approaches - convenience, mystery clients and overt, within a defined area and sampling frame in Enugu metropolis. The active pharmaceutical ingredients were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. Results were expressed as percentage of APIs stated on the packaging and used to categorise each sample as acceptable quality, substandard, degraded, or falsified. RESULTS: Content analysis of 3024 samples purchased from 421 outlets using convenience (n=200), mystery (n=1,919) and overt (n=905) approaches, showed overall 90.8% ACAs to be of acceptable quality, 6.8% substandard, 1.3% degraded and 1.2% falsified. Convenience sampling yielded a significantly higher prevalence of poor quality ACAs, but was not evident by the mystery and overt sampling strategies both of which yielded results that were comparable between each other. Artesunate (n=135; 4 falsified) and dihydroartemisinin (n=14) monotherapy tablets, not recommended by WHO, were also identified. CONCLUSION: Randomised sampling identified fewer falsified ACAs than previously reported by convenience approaches. Our findings emphasise the need for specific consideration to be given to sampling frame and sampling approach if representative information on drug quality is to be obtained. |
Collaborative health and enforcement operations on the quality of antimalarials and antibiotics in Southeast Asia
Yong YL , Plancon A , Lau YH , Hostetler DM , Fernandez FM , Green MD , Sounvoravong S , Nara S , Boravann M , Dumrong T , Bangsawan N , Low MY , Lim CC , Ai RL , Newton PN . Am J Trop Med Hyg 2015 92 105-112 Counterfeit (or falsified) and substandard medicines pose a major public health risk. We describe the findings of Operation Storm I and II conducted in 2008-2009 to combat counterfeit medicines through partnership between national customs, Drug Regulatory Agencies (DRAs), and police in Cambodia, Indonesia, Laos, Myanmar, Singapore, Thailand, and Vietnam. Samples were obtained from seizures and market surveillance by national DRAs. Laboratory analysis using spectroscopic and chromatographic techniques and examination of packaging were performed. Ninety-three suspect antibiotics and 95 antimalarial samples were collected. Of the 93 antibiotics, 29 (31%) had % active pharmaceutical ingredient content (%API) < 85% or > 115% (including one counterfeit). Of the 95 antimalarials, 30 (32%) had %API < 85 > 115% API (including one counterfeit). A significant minority of samples, antimalarials (13%) and antibiotics (15%), were collected in plastic bags with minimal or no labeling. Of 20 ampicillin samples, 13 (65%) contained < 85% API (with one counterfeit containing additional amoxicillin). Of 34 oral artesunate samples, 7 (21%) contained %API out of the 85-115% range. Coordinated and synergistic partnership adopted by the participating countries, International Criminal Police Organization (INTERPOL), World Health Organization (WHO), and laboratories facilitated a platform for discussions and intelligence sharing, helping to improve each participating country's capacity to combat poor-quality medicines. |
A repeat random survey of the prevalence of falsified and substandard antimalarials in the Lao PDR: a change for the better
Tabernero P , Mayxay M , Culzoni MJ , Dwivedi P , Swamidoss I , Allan EL , Khanthavong M , Phonlavong C , Vilayhong C , Yeuchaixiong S , Sichanh C , Sengaloundeth S , Kaur H , Fernandez FM , Green MD , Newton PN . Am J Trop Med Hyg 2015 92 95-104 In 2003, a stratified random sample survey was conducted in the Lao People's Democratic Republic (Laos) to study the availability and quality of antimalarials in the private sector. In 2012, this survey was repeated to allow a statistically valid analysis of change through time. The counterfeit detection device 3 (CD-3) was used to assess packaging quality in the field. The availability of oral artesunate monotherapies had significantly decreased from 22.9% (22) of 96 outlets in southern Laos in 2003 to 4.8% (7) of 144 outlets in 2012 (P < 0.0001). All the samples collected in 2012 survey contained the correct active pharmaceutical ingredients (APIs) in contrast to the 21 (84%) falsified artesunate samples found in the 2003 survey. Although none of the medicines found in 2012 survey had evidence for falsification, 25.4% (37) of the samples were outside the 90-110% pharmacopeial limits of the label claim, suggesting that they were substandard or degraded. Results obtained from this survey show that patients are still exposed to poorly manufactured drugs or to ineffective medicines such as chloroquine. The quality of artemisinin-based combination therapies (ACTs) used in Laos needs to be monitored; since falsified ACTs would have devastating consequences in public health. |
Quality of antimalarials at the epicenter of antimalarial drug resistance: results from an overt and mystery client survey in Cambodia
Yeung S , Lawford HL , Tabernero P , Nguon C , van Wyk A , Malik N , DeSousa M , Rada O , Boravann M , Dwivedi P , Hostetler DM , Swamidoss I , Green MD , Fernandez FM , Kaur H . Am J Trop Med Hyg 2015 92 39-50 Widespread availability of monotherapies and falsified antimalarials is thought to have contributed to the historical development of multidrug-resistant malaria in Cambodia. This study aimed to document the quality of artemisinin-containing antimalarials (ACAs) and to compare two methods of collecting antimalarials from drug outlets: through open surveyors and mystery clients (MCs). Few oral artemisinin-based monotherapies and no suspected falsified medicines were found. All 291 samples contained the stated active pharmaceutical ingredient (API) of which 69% were considered good quality by chemical analysis. Overall, medicine quality did not differ by collection method, although open surveyors were less likely to obtain oral artemisinin-based monotherapies than MCs. The results are an encouraging indication of the positive impact of the country's efforts to tackle falsified antimalarials and artemisinin-based monotherapies. However, poor-quality medicines remain an ongoing challenge that demands sustained political will and investment of human and financial resources. |
Desorption atmospheric pressure photoionization and direct analysis in real time coupled with travelling wave ion mobility mass spectrometry
Rasanen RM , Dwivedi P , Fernandez FM , Kauppila TJ . Rapid Commun Mass Spectrom 2014 28 (21) 2325-36 RATIONALE: Ambient mass spectrometry (MS) is a tool for screening analytes directly from sample surfaces. However, background impurities may complicate the spectra and therefore fast separation techniques are needed. Here, we demonstrate the use of travelling wave ion mobility spectrometry in a comparative study of two ambient MS techniques. METHODS: Desorption atmospheric pressure photoionization (DAPPI) and direct analysis in real time (DART) were coupled with travelling wave ion mobility mass spectrometry (TWIM-MS) for highly selective surface analysis. The ionization efficiencies of DAPPI and DART were compared. Test compounds were: bisphenol A, benzo[a]pyrene, ranitidine, cortisol and alpha-tocopherol. DAPPI-MS and DART-TWIM-MS were also applied to the analysis of chloroquine from dried blood spots, and alpha-tocopherol from almond surface, and DAPPI-TWIM-MS was applied to analysis of pharmaceuticals and multivitamin tablets. RESULTS: DAPPI was approximately 100 times more sensitive than DART for bisphenol A and 10-20 times more sensitive for the other compounds. The limits of detection were between 30-290 and 330-8200 fmol for DAPPI and DART, respectively. Also, from the authentic samples, DAPPI ionized chloroquine and alpha-tocopherol more efficiently than DART. The mobility separation enabled the detection of species with low signal intensities, e.g. thiamine and cholecalciferol, in the DAPPI-TWIM-MS analysis of multivitamin tablets. CONCLUSIONS: DAPPI ionized the studied compounds of interest more efficiently than DART. For both DAPPI and DART, the mobility separation prior to MS analysis reduced the amount of chemical noise in the mass spectrum and significantly increased the signal-to-noise ratio for the analytes. |
Falsified medicines in Africa: all talk, no action
Newton PN , Tabernero P , Dwivedi P , Culzoni MJ , Monge ME , Swamidoss I , Mildenhall D , Green MD , Jähnke R , de Oliveira MDS , Simao J , White NJ , Fernández FM . Lancet Glob Health 2014 2 (9) e509-10 Poor-quality medicines and medical products, both substandard and falsified, cause avoidable morbidity, mortality, drug resistance, and loss of faith in health systems, especially in low-income and middle-income countries.1, 2, 3 We report the analysis of two falsified medicines from Angola and discuss what lessons such a discovery could hold. | The tablets were seized at Luanda docks in June, 2012, after failing Minilab testing.4, 5 The seized shipment was enormous (1·4 million packets), and hidden in loudspeakers in a container from China.4 One sample was labelled as an adult course of the vital antimalarial drug artemether-lumefantrine, and as being manufactured by “Novartis Pharmaceutical Corporation”; it also bore an Affordable Medicines Facility—malaria logo (figure). Another sample was labelled as the broad-spectrum anthelmintic mebendazole, and as being manufactured by “Janssen-Cilag SpA”. |
Mind the gaps - the epidemiology of poor-quality anti-malarials in the malarious world - analysis of the WorldWide Antimalarial Resistance Network database
Tabernero P , Fernandez FM , Green M , Guerin PJ , Newton PN . Malar J 2014 13 139 BACKGROUND: Poor quality medicines threaten the lives of millions of patients and are alarmingly common in many parts of the world. Nevertheless, the global extent of the problem remains unknown. Accurate estimates of the epidemiology of poor quality medicines are sparse and are influenced by sampling methodology and diverse chemical analysis techniques. In order to understand the existing data, the Antimalarial Quality Scientific Group at WWARN built a comprehensive, open-access, global database and linked Antimalarial Quality Surveyor, an online visualization tool. Analysis of the database is described here, the limitations of the studies and data reported, and their public health implications discussed. METHODS: The database collates customized summaries of 251 published anti-malarial quality reports in English, French and Spanish by time and location since 1946. It also includes information on assays to determine quality, sampling and medicine regulation. RESULTS: No publicly available reports for 60.6% (63) of the 104 malaria-endemic countries were found. Out of 9,348 anti-malarials sampled, 30.1% (2,813) failed chemical/packaging quality tests with 39.3% classified as falsified, 2.3% as substandard and 58.3% as poor quality without evidence available to categorize them as either substandard or falsified. Only 32.3% of the reports explicitly described their definitions of medicine quality and just 9.1% (855) of the samples collected in 4.6% (six) surveys were conducted using random sampling techniques. Packaging analysis was only described in 21.5% of publications and up to twenty wrong active ingredients were found in falsified anti-malarials. CONCLUSIONS: There are severe neglected problems with anti-malarial quality but there are important caveats to accurately estimate the prevalence and distribution of poor quality anti-malarials. The lack of reports in many malaria-endemic areas, inadequate sampling techniques and inadequate chemical analytical methods and instrumental procedures emphasizes the need to interpret medicine quality results with caution. The available evidence demonstrates the need for more investment to improve both sampling and analytical methodology and to achieve consensus in defining different types of poor quality medicines. |
Viable Staphylococcus aureus quantitation using 15N metabolically-labeled bacteriophage amplification coupled with a multiple reaction monitoring proteomic workflow
Pierce CL , Rees JC , Fernandez FM , Barr JR . Mol Cell Proteomics 2011 11 (1) M111 012849 A multiple reaction monitoring liquid chromatography (LC) method with tandem mass spectrometric detection (MS/MS) for quantitation of Staphylococcus aureus via phage amplification detection (PAD) is described. This PAD method enables rapid and accurate quantitation of viable S. aureus by detecting an amplified capsid protein from a specific phage. A known amount of metabolically-labeled (15)N reference bacteriophage, utilized as the input phage and as the internal standard for quantitation, was spiked into S. aureus samples. Following a 2-h incubation, the sample was subjected to a 3-min rapid trypsin digest and analyzed by high-throughput LC-MS/MS targeting peptides unique to both the (15)N (input phage) and (14)N (progeny phage) capsid proteins. Quantitation was achieved by comparing peak areas of target peptides from the metabolically labeled (15)N bacteriophage peptide internal standard with that of the wild-type (14)N peptides that were produced by phage amplification and subsequent digestion when the host bacteria was present. This approach is based on the fact that a labeled species differs from the unlabeled one in terms of its mass but exhibits almost identical chemical properties such as ion yields and retention times. A 6-point calibration curve for S. aureus concentration was constructed with standards ranging from 5.0x10(4) CFU mL(-1) to 2.0x10(6) CFU mL(-1), with the (15)N reference phage spiked at a concentration of 1.0x10(9) PFU mL(-1). Amplification with (15)N bacteriophage coupled with LC-MS/MS detection offers speed (3 h total analysis time), sensitivity (LOD: < 5.0 x 10(4) CFU mL(-1)), accuracy, and precision for quantitation of S. aureus. |
Detection of Staphylococcus aureus using (15)N-labeled bacteriophage amplification coupled with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry
Pierce CL , Rees JC , Fernandez FM , Barr JR . Anal Chem 2011 83 (6) 2286-93 A novel approach to rapid bacterial detection using an isotopically labeled (15)N bacteriophage and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) is introduced. Current phage amplification detection (PAD) via mass spectrometric analysis is limited because host bacteria must be inoculated with low phage titers in such a way that initial infecting phage concentrations must be below the detection limit of the instrument, thus lengthening incubation times. Additionally, PAD techniques cannot distinguish inoculate input phage from output phage which can increase the possibility of false positive results. Here, we report a rapid and accurate PAD approach for identification of Staphylococcus aureus via detection of bacteriophage capsid proteins. This approach uses both a wild-type (14)N and a (15)N-isotopically labeled S. aureus-specific bacteriophage. High (15)N phage titers, above our instrument's detection limits, were used to inoculate S. aureus. MALDI-TOF MS detection of the (14)N progeny capsid proteins in the phage-amplified culture indicated the presence of the host bacteria. Successful phage amplification was observed after 90 min of incubation. The amplification was observed by both MALDI-TOF MS analysis and by standard plaque assay measurements. This method overcomes current limitations by improving analysis times while increasing selectivity when compared to previously reported PAD methodologies. |
Impact of poor-quality medicines in the 'developing' world
Newton PN , Green MD , Fernandez FM . Trends Pharmacol Sci 2010 31 (3) 99-101 Since our ancestors began trading several millennia ago, counterfeit and substandard medicines have been a recurring problem, with history punctuated by crises in the supply of anti-microbials, such as fake cinchona bark in the 1600s and fake quinine in the 1800s. Unfortunately this problem persists, in particular afflicting unsuspecting patients in 'developing' countries. Poor-quality drugs are a vital (but neglected) public health problem. They contribute to a 'crevasse' between the enormous effort in therapeutic research and policy decisions and implementation of good-quality medicines. |
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