Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-17 (of 17 Records) |
Query Trace: Green MD[original query] |
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A random survey of the prevalence of falsified and substandard antibiotics in the Lao PDR
Tabernero P , Swamidoss I , Mayxay M , Khanthavong M , Phonlavong C , Vilayhong C , Yeuchaixiong S , Sichanh C , Sengaloundeth S , Green MD , Newton PN . J Antimicrob Chemother 2019 74 (8) 2417-2425 OBJECTIVES: In 2012, a stratified random survey, using mystery shoppers, was conducted to investigate the availability and quality of antibiotics sold to patients in the private sector in five southern provinces of the Lao People's Democratic Republic (Laos). METHODS: A total of 147 outlets were sampled in 10 districts. The active pharmaceutical ingredient (API) content measurements for 909 samples, including nine APIs (amoxicillin, ampicillin, ceftriaxone, ciprofloxacin, doxycycline, ofloxacin, sulfamethoxazole, tetracycline and trimethoprim), were determined using HPLC. RESULTS: All the analysed samples contained the stated API and we found no evidence for falsification. All except one sample had all the units tested with %API values between 75% and 125% of the content stated on the label. However, we identified the presence of substandard antibiotics: 19.6% (201/1025) of samples had their units outside the 90%-110% content of the label claim and 60.2% (617/1025) of the samples had units outside of the International Pharmacopoeia uniformity of content limit range. Amoxicillin had a high number of samples [67.1% (151)] with units above the limit range, followed by ciprofloxacin [58.8% (10)] and ofloxacin [57.4% (39)]. Ceftriaxone, trimethoprim and sulfamethoxazole had the highest number of samples with low API content: 57.1% (4), 51.6% (64) and 34.7% (43), respectively. Significant differences in %API were found between stated countries of manufacture and stated manufacturers. CONCLUSIONS: With the global threat of antimicrobial resistance to patient outcomes, greater understanding of the role of poor-quality antibiotics is needed. Substandard antibiotics will have reduced therapeutic efficacy, impacting public health and control of bacterial infections. |
Monitoring and predicting net longevity by measuring surface levels of insecticide: Implementing a faster, cost effective, nondestructive, and field-ready alternative to the World Health Organization Cone Test Bioassay
Calle DA , Rua-Uribe GL , Osorio L , Pineros-Jimenez JG , Swamidoss I , Vizcaino L , Beach R , Green MD . Am J Trop Med Hyg 2018 99 (4) 1003-1005 An important component of malaria control programs is the ability to assess the effectiveness of the insecticide in insecticide-treated nets (ITNs) during normal usage. The standard technique to measure insecticidal activity is the World Health Organization (WHO) cone test, which in many circumstances, may be difficult to implement. We have evaluated an alternative technique, the colorimetric field test (CFT) on a group of 24-month-old Permanet((R)) 2.0 nets collected in Colombia. The CFT, which measures surface levels (SL) of deltamethrin is compared with standard high-performance liquid chromatography (HPLC) and the WHO cone test. Effective concentrations of deltamethrin for 80% mortality (EC80) were determined from the CFT and HPLC results. Distribution of insecticide SL after 24 months of use reveal that sampling of the midsection best represents the condition of the entire net. We conclude that the CFT is a practical alternative to the WHO cone test for assessing ITN efficacy. |
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. |
Quality of Artemisinin-Containing Antimalarials in Tanzania's Private Sector--Results from a Nationally Representative Outlet Survey
ACT Consortium Drug Quality Project Team and the IMPACT2 Study Team , Swamidoss I , Green MD , Dwivedi P , Kachur SP . Am J Trop Med Hyg 2015 92 75-86 Ensuring that artemisinin-containing antimalarials (ACAs) are of good quality is a key component of effective malaria treatment. There are concerns that a high proportion of ACAs are falsified or substandard, though estimates are rarely based on representative data. During a nationally representative survey in Tanzania, ACAs were purchased from private retail drug outlets, and the active pharmaceutical ingredient (API) was measured. All 1,737 ACAs contained the labeled artemisinin derivative, with 4.1% being outside the 85-115% artemisinin API range defined as acceptable quality. World Health Organization (WHO) prequalified drugs had 0.1 times the odds of being poor quality compared with non-prequalified ACAs for the artemisinin component. When partner components of combination therapies were also considered, 12.1% were outside the acceptable API range, and WHO prequalified ACAs had 0.04 times the odds of being poor quality. Although the prevalence of poor quality ACAs was lower than reported elsewhere, the minority of samples found to be substandard is a cause for concern. Improvements in quality could be achieved by increasing the predominance of WHO prequalified products in the market. Continued monitoring of quality standards is essential. |
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. |
N-acetyl cysteine and mushroom Agaricus sylvaticus supplementation decreased parasitaemia and pulmonary oxidative stress in a mice model of malaria
Quadros Gomes BA , da Silva LF , Quadros Gomes AR , Moreira DR , Dolabela MF , Santos RS , Green MD , Carvalho EP , Percario S . Malar J 2015 14 (1) 202 BACKGROUND: Malaria infection can cause high oxidative stress, which could lead to the development of severe forms of malaria, such as pulmonary malaria. In recent years, the role of reactive oxygen species in the pathogenesis of the disease has been discussed, as well as the potential benefit of antioxidants supplementation. The aim of this study was to investigate the effects of N-acetyl cysteine (NAC) or mushroom Agaricus sylvaticus supplementation on the pulmonary oxidative changes in an experimental model of malaria caused by Plasmodium berghei strain ANKA. METHODS: Swiss male mice were infected with P. berghei and treated with NAC or AS. Samples of lung tissue and whole blood were collected after one, three, five, seven or ten days of infection for the assessment of thiobarbituric acid reactive substances (TBARS), trolox equivalent antioxidant capacity (TEAC), nitrites and nitrates (NN) and to assess the degree of parasitaemia. RESULTS: Although parasitaemia increased progressively with the evolution of the disease in all infected groups, there was a significant decrease from the seventh to the tenth day of infection in both antioxidant-supplemented groups. Results showed significant higher levels of TEAC in both supplemented groups, the highest occurring in the group supplemented with A. sylvaticus. In parallel, TBARS showed similar levels among all groups, while levels of NN were higher in animals supplemented with NAC in relation to the positive control groups and A. sylvaticus, whose levels were similar to the negative control group. CONCLUSION: Oxidative stress arising from plasmodial infection was attenuated by supplementation of both antioxidants, but A. sylvaticus proved to be more effective and has the potential to become an important tool in the adjuvant therapy of malaria. |
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. |
Integration of novel low-cost colorimetric, laser photometric, and visual fluorescent techniques for rapid identification of falsified medicines in resource-poor areas: application to artemether-lumefantrine
Green MD , Hostetler DM , Nettey H , Swamidoss I , Ranieri N , Newton PN . Am J Trop Med Hyg 2015 92 8-16 The availability of falsified antimalarial drugs can be reduced with effective drug regulatory agencies and proper enforcement. Fundamental to these agencies taking action, rapid identification must be made as soon as they appear in the market place. Since falsified antimalarials occur mostly in developing countries, performing drug analysis presents itself with unique challenges. A fundamental factor in choosing a useful technique is affordability and simplicity. Therefore, we suggest a three-tiered drug evaluation strategy for identifying a falsified drug in resource-poor areas. Tier I is a simple comparison of a tablet's weight and dimensions with official specifications. Tier II uses inexpensive photometric devices (laser and fluorescence) to evaluate a tablet. Suspicious samples from Tier I and II assessments are then subjected to a colorimetric assay for active ingredients identification and quantification. In this article, we evaluate a novel colorimetric assay for the simultaneous assessment of both lumefantrine and artemether in co-formulated Coartem tablets, and integrate the method with two novel, low-cost, fluorescence and laser photometric devices. Image analysis software is used for the assessments. Although artemether-lumefantrine is used as an example, the strategy may be adapted to other medicines. |
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. |
Quality assurance of drugs used in clinical trials: proposal for adapting guidelines
Newton PN , Schellenberg D , Ashley EA , Ravinetto R , Green MD , Kuile FO , Tabernero P , White NJ , Guerin PJ . BMJ 2015 350 h602 Paul Newton and colleagues propose that clinical trial guidelines should include a requirement to assess and state the quality of the drugs and other medical products used |
Evaluation of a new handheld instrument for the detection of counterfeit artesunate by visual fluorescence comparison
Ranieri N , Tabernero P , Green MD , Verbois L , Herrington J , Sampson E , Satzger RD , Phonlavong C , Thao K , Newton PN , Witkowski MR . Am J Trop Med Hyg 2014 91 (5) 920-4 There is an urgent need for accurate and inexpensive handheld instruments for the evaluation of medicine quality in the field. A blinded evaluation of the diagnostic accuracy of the Counterfeit Detection Device 3 (CD-3), developed by the US Food and Drug Administration Forensic Chemistry Center, was conducted in the Lao People's Democratic Republic. Two hundred three samples of the oral antimalarial artesunate were compared with authentic products using the CD-3 by a trainer and two trainees. The specificity (95% confidence interval [95% CI]), sensitivity (95% CI), positive predictive value (95% CI), and negative predictive value (95% CI) of the CD-3 for detecting counterfeit (falsified) artesunate were 100% (93.8-100%), 98.4% (93.8-99.7%), 100% (96.2-100%), and 97.4% (90.2-99.6%), respectively. Interobserver agreement for 203 samples of artesunate was 100%. The CD-3 holds promise as a relatively inexpensive and easy to use instrument for field evaluation of medicines, potentially empowering drug inspectors, customs agents, and pharmacists. |
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”. |
Evaluation of a rapid colorimetric field test to assess the effective life of long-lasting insecticide-treated mosquito nets in the Lao PDR
Green MD , Mayxay M , Beach R , Pongvongsa T , Phompida S , Hongvanthong B , Vanisaveth V , Newton PN , Vizcaino L , Swamidoss I . Malar J 2013 12 (1) 57 BACKGROUND: Malaria morbidity and mortality have been significantly reduced through the proper use of insecticide-treated mosquito nets, but the extra protection afforded by the insecticide diminishes over time. The insecticide depletion rates vary according to location where wash frequency and wear are influenced by cultural habits as well as the availability of water. Monitoring of available insecticides on the net surface is essential for determining the effective life of the net. Therefore, a rapid and inexpensive colorimetric field test for cyanopyrethroids (Cyanopyrethroid Field Test or CFT) was used to measure surface levels of deltamethrin on insecticide-coated polyester nets (PowerNetsTM) in rural Lao PDR over a two-year period. METHODS: Net surface levels of deltamethrin were measured by wiping the net with filter paper and measuring the adsorbed deltamethrin using the CFT. A relationship between surface levels of deltamethrin and whole net levels was established by comparing results of the CFT with whole levels assayed by high-performance liquid chromatography (HPLC). An effective deltamethrin surface concentration (EC80) was determined by comparing mosquito mortality (WHO Cone Test) with CFT and HPLC results. Five positions (roof to bottom) on each of 23 matched nets were assayed for deltamethrin surface levels at 6, 12, and 24 months. Mosquito mortality assays (WHO Cone Tests) were performed on a subset of eleven 24-month old nets and compared with the proportion of failed nets as predicted by the CFT. RESULTS: At six months, the nets retained about 80% of the baseline (new net) levels of deltamethrin with no significant differences between net positions. At 12 months, ~15-40%, and at 24 months <10% of deltamethrin was retained on the nets, with significant differences appearing between positions. Results from the CFT show that 93% of the nets failed (deltamethrin surface levels ≤ EC80) at 24 months. This value is in agreement with 91% failure as determined by the WHO Cone Test on a subset of 11 nets. The CFT results show that 50% of the nets from Laos failed at 12 months of normal use. CONCLUSION: The CFT is a useful and accurate indicator of net efficacy and may be substituted for mosquito bioassays. |
Oxidative stress in malaria
Percario S , Moreira DR , Gomes BA , Ferreira ME , Goncalves AC , Laurindo PS , Vilhena TC , Dolabela MF , Green MD . Int J Mol Sci 2012 13 (12) 16346-72 Malaria is a significant public health problem in more than 100 countries and causes an estimated 200 million new infections every year. Despite the significant effort to eradicate this dangerous disease, lack of complete knowledge of its physiopathology compromises the success in this enterprise. In this paper we review oxidative stress mechanisms involved in the disease and discuss the potential benefits of antioxidant supplementation as an adjuvant antimalarial strategy. |
An outbreak of Plasmodium falciparum malaria in U.S. Marines deployed to Liberia
Whitman TJ , Coyne PE , Magill AJ , Blazes DL , Green MD , Milhous WK , Burgess TH , Freilich D , Tasker SA , Azar RG , Endy TP , Clagett CD , Deye GA , Shanks GD , Martin GJ . Am J Trop Med Hyg 2010 83 (2) 258-265 In 2003, 44 U.S. Marines were evacuated from Liberia with either confirmed or presumed Plasmodium falciparum malaria. An outbreak investigation showed that only 19 (45%) used insect repellent, 5 (12%) used permethrin-treated clothing, and none used bed netting. Adherence with weekly mefloquine (MQ) was reported by 23 (55%). However, only 4 (10%) had serum MQ levels high enough to correlate with protection (> 794 ng/mL), and 9 (22%) had evidence of steady-state kinetics (MQ carboxy metabolite/MQ > 3.79). Tablets collected from Marines met USP identity and dissolution specifications for MQ. Testing failed to identify P. falciparum isolates with MQ resistance. This outbreak resulted from under use of personal protective measures and inadequate adherence with chemophrophylaxis. It is essential that all international travelers make malaria prevention measures a priority, especially when embarking to regions of the world with high transmission intensity such as west Africa."Good doctors are of no use without good discipline. More than half the battle against disease is not fought by doctors, but by regimental officers. It is they who see that the daily dose of mepacrine (anti-malarial chemoprophylactic drug used in WW II) is taken...if mepacrine was not taken, I sacked the commander. I only had to sack three; by then the rest had got my meaning." -Lieutenant General William Slim (1891-1970), Burma Campaign, 1943. |
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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