title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Research, London School of Hygiene & Tropical Medicine, Keppel Street, London, United Kingdom.
authors.forename: Harparkash
authors.initials: H
authors.lastname: Kaur
authors.affiliation: Department of Clinical Research, London School of Hygiene & Tropical Medicine, Keppel Street, London, United Kingdom.
authors.forename: Elizabeth Louise
authors.initials: EL
authors.lastname: Allan
authors.affiliation: Department of Global Health and Development, London School of Hygiene & Tropical Medicine, Tavistock Place, London, United Kingdom.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Mamadu
authors.affiliation: Department of Clinical Research, London School of Hygiene & Tropical Medicine, Keppel Street, London, United Kingdom.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Hall
authors.affiliation: Department of Pharmacology and Therapeutics, University of Nigeria, Enugu, Nigeria.
authors.forename: Ogochukwu
authors.initials: O
authors.lastname: Ibe
authors.affiliation: Department of Global Health and Development, London School of Hygiene & Tropical Medicine, Tavistock Place, London, United Kingdom.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Sherbiny
authors.affiliation: Department of Clinical Research, London School of Hygiene & Tropical Medicine, Keppel Street, London, United Kingdom.
authors.forename: Albert
authors.initials: A
authors.lastname: van Wyk
authors.affiliation: Department of Clinical Research, London School of Hygiene & Tropical Medicine, Keppel Street, London, United Kingdom; Department of Global Health and Development, London School of Hygiene & Tropical Medicine, Tavistock Place, London, United Kingdom.
authors.forename: Shunmay
authors.initials: S
authors.lastname: Yeung
authors.affiliation: Division of Parasitic Diseases and Malaria, US Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Isabel
authors.initials: I
authors.lastname: Swamidoss
authors.affiliation: Division of Parasitic Diseases and Malaria, US Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Green
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Prabha
authors.initials: P
authors.lastname: Dwivedi
authors.affiliation: Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, Argentina.
authors.forename: Maria Julia
authors.initials: MJ
authors.lastname: Culzoni
authors.affiliation: Department of Disease Control, London School of Hygiene & Tropical Medicine, Keppel Street, London, United Kingdom.
authors.forename: Siân
authors.initials: S
authors.lastname: Clarke
authors.affiliation: Department of Disease Control, London School of Hygiene & Tropical Medicine, Keppel Street, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Schellenberg
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors.forename: Facundo M
authors.initials: FM
authors.lastname: Fernández
authors.affiliation: Department of Pharmacology and Therapeutics, University of Nigeria, Enugu, Nigeria.
authors.forename: Obinna
authors.initials: O
authors.lastname: Onwujekwe
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000592:standards* / Q000627:therapeutic use*; D037621:Artemisinins / Q000032:analysis; D000077332:Artesunate; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D009549:Nigeria; D010594:Pharmacies; D017149:Private Sector; D011633:Public Facilities; D011786:Quality Control; D012307:Risk Factors; D013607:Tablets
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D013607:Tablets; D000077332:Artesunate; C031327:artemisinin