Researchers found 1.2% of the samples to be falsified and 1.3% to be degraded, but raised bigger concerns about 6.8% being of substandard manufacture, leaving patients at risk of not receiving the correct treatment dose and potentially contributing to the development of resistance to the main drug used to treat malaria.
The drug quality team of the Artemisinin-based Combination Therapy (ACT) Consortium at the London School of Hygiene & Tropical Medicine analysed 3,024 antimalarials containing artemisinin (the component that makes malaria treatment effective) from Enugu Metropolis, South East Nigeria, which has a population of 3.3 million. Nigeria is the single most heavily malaria-burdened country in the world, with 48 million malaria cases and 180,000 deaths per year.
Dr Harparkash Kaur, from the London School of Hygiene & Tropical Medicine, lead investigator of the drug quality programme of the ACT Consortium, said: "Although these results raise concerns, they are reassuring in comparison with previous reports that found that more than 35% of antimalarials in sub-Saharan Africa failed chemical content analysis - in other words, were poor quality. This may be because those reports predominantly used a "convenience" approach to select samples for analysis, which may not be representative of the places where patients buy their medicines."
The team purchased medicines from 421 outlets in Enugu including pharmacies, patent medicine vendors, and public health facilities. In addition to "convenience" sampling, which lacks systematic guidance on which outlets to sample from, samples were also bought from a representative sample of outlets. Two approaches were used in the representative sampling: a covert approach, using "mystery clients" in which researchers pretended to be patients with malaria, or their relatives, asking to buy medicines; and an "overt" approach, where researchers told vendors openly that they were going to analyse the quality of their malaria medicines.
Each sample was analysed in three independent laboratories in the UK and USA and classified as acceptable quality, falsified (fake drugs which do not contain the stated active pharmaceutical ingredient or API), substandard (which contain inadequate amounts of the active ingredients), or degraded (decomposition of the API by poor storage conditions, such as heat and humidity).
All three sampling methods detected falsified drugs, but the prevalence was higher in samples purchased using the convenience approach.
Falsified samples contained chemicals other than the stated API, such as chlorzoxazone (a muscle relaxant), ciprofloxacin (an antibiotic) or acetaminophen (a commonly used painkiller).
The team also identified artemisinin-based monotherapy tablets, which are no longer recommended by the World Health Organization because they do not include the partner compound that makes it an effective artemisinin-based combination therapy. Some of these monotherapies were also falsified.
Substandard or degraded drugs were more prevalent than falsified ones in Enugu. Poor quality drugs were frequently found in patent medicine vendors - also known as drug shops, which are the main source of treatment for most patients - rather than in pharmacies.
Study co-author Prof. Obinna Onwujekwe from the University of Nigeria, Enugu said: "The results show that the health system actors should be eternally vigilant in Nigeria and in other countries to ensure that sub-standard drugs do not impede or erode gains made in malaria treatment. Drug regulatory authorities and their partners should intensify drug quality monitoring activities with appropriate sanctions for defaulters."
The ACT Consortium's large drug quality programme, which has analysed over 10,000 samples from six malaria endemic countries over five years, has recently published results from Tanzania and Cambodia, where substandard medicines were of similar concern but where no falsified medicines were found. Results from Equatorial Guinea, Ghana and Rwanda will be published in the next few months.
INFORMATION:
The ACT Consortium is funded by a grant from the Bill & Melinda Gates Foundation to London School of Hygiene & Tropical Medicine.
For more information or to request interviews contact the press office at the London School of Hygiene & Tropical Medicine: press@lshtm.ac.uk and +44 (0)20 7927 2802.
Notes to Editors:
* Harparkash Kaur, Elizabeth Louise Allan, Ibrahim Mamadu, Zoe Hall, Ogochukwu Ibe, Mohamed El Sherbiny, Albert van Wyk, Shunmay Yeung, Siân Clarke, Isabel Swamidoss, Michael D Green, Prabha Dwivedi, Maria Julia Culzoni, David Schellenberg, Obinna Onwujekwe. 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. PLOS ONE. DOI: 10.1371/journal.pone.0125577
Falsified drugs carry false representations of their source or identity, and often contain none of the stated active ingredient(s). Counterfeit medicines are medicines that do not comply with intellectual property rights or that infringe trademark law.
Researchers used the analytical technique of high performance liquid chromatography (HPLC) for the quantitative analysis and mass spectrometry for the qualitative analysis. USP and WHO pharmacopeia rules define drugs as being poor quality if they contain less than 90% or more than 110% of the stated amount of the API. The ACT Consortium adopted the slightly less stringent range of 85% to 115% API as acceptable. Results are sensitive to these limits.
Collaborating institutions: Enugu State Ministry of Health, Nigeria, University of Nigeria, US Centers for Disease Control and Prevention, USA, Georgia Institute of Technology, USA.
About the ACT Consortium
The ACT Consortium is an international research collaboration working on 25 projects in 10 countries to answer key questions on malaria drug delivery. Since initiating activities in 2008, the Consortium has been working to optimise the use of Artemisinin-based Combination Therapy (ACT), the first-line treatment for the most dangerous form of malaria recommended by the World Health Organization. The projects investigate ways to improve the access and targeting of ACTs, as well as assessing their safety and quality. The ACT Consortium is based at the London School of Hygiene & Tropical Medicine and a member of the School's Malaria Centre. Learn more about the drug quality programme at http://www.actconsortium.org/drugquality and watch a video at https://vimeo.com/125049233. The ACT Consortium will host a drug quality event on 28 May 2015 in Geneva, Switzerland. Find out more information on the above website.
About the London School of Hygiene & Tropical Medicine
The London School of Hygiene & Tropical Medicine is a world-leading centre for research and postgraduate education in public and global health, with 3,900 students and more than 1,000 staff working in over 100 countries. The School is one of the highest-rated research institutions in the UK, and was recently cited as the world's leading research-focused graduate school. Our mission is to improve health and health equity in the UK and worldwide; working in partnership to achieve excellence in public and global health research, education and translation of knowledge into policy and practice. http://www.lshtm.ac.uk
