title: Characterizing the insecticide resistance of Anopheles gambiae in Mali.
abstract: BACKGROUND
  The impact of indoor residual spraying (IRS) and long-lasting insecticide nets (LLINs), key components of the national malaria control strategy of Mali, is threatened by vector insecticide resistance. The objective of this study was to assess the level of insecticide resistance in Anopheles gambiae sensu lato populations from Mali against four classes of insecticide recommended for IRS: organochlorines (OCs), pyrethroids (PYs), carbamates (CAs) and organophosphates (OPs). Characterization of resistance was done in 13 sites across southern Mali and assessed presence and distribution of physiological mechanisms that included target-site modifications: knockdown resistance (kdr) and altered acetycholinesterase (AChE), and/or metabolic mechanisms: elevated esterases, glutathione S-transferases (GSTs), and monooxygenases.
  
  
  METHODS
  The World Health Organization (WHO) tube test was used to determine phenotypic resistance of An. gambiae s.l. to: dichlorodiphenyltrichloroethane (DDT) (OC), deltamethrin (PY), lambda-cyhalothrin (PY), bendiocarb (CA), and fenitrothion (OP). Identification of sibling species and presence of the ace-1 (R) and Leu-Phe kdr, resistance-associated mutations, were determined using polymerase chain reaction (PCR) technology. Biochemical assays were conducted to detect increased activity of GSTs, oxidases and esterases.
  
  
  RESULTS
  Populations tested showed high levels of resistance to DDT in all 13 sites, as well as increased resistance to deltamethrin and lambda-cyhalothrin in 12 out of 13 sites. Resistance to fenitrothion and bendiocarb was detected in 1 and 4 out of 13 sites, respectively. Anopheles coluzzii, An. gambiae sensu stricto and Anopheles arabiensis were identified with high allelic frequencies of kdr in all sites where each of the species were found (13, 12 and 10 sites, respectively). Relatively low allelic frequencies of ace-1 (R) were detected in four sites where this assessment was conducted. Evidence of elevated insecticide metabolism, based on oxidase, GSTs and esterase detoxification, was also documented.
  
  
  CONCLUSIONS
  Multiple insecticide-resistance mechanisms have evolved in An. coluzzii, An. gambiae s.s. and An. arabiensis in Mali. These include at least two target site modifications: kdr, and ace-1 (R) , as well as elevated metabolic detoxification systems (monooxygenases and esterases). The selection pressure for resistance could have risen from the use of these insecticides in agriculture, as well as in public health. Resistance management strategies, based on routine resistance monitoring to inform insecticide-based malaria vector control in Mali, are recommended.
authors: PMI Africa Indoor Residual Spraying Project, Abt Associates, Mali, Cite du Niger. BP: 34, Bamako, Mali. Moussa_Cisse@africairs.net.
authors: Moussa B M
authors: MB
authors: Cisse
authors: PMI Africa Indoor Residual Spraying Project, Abt Associates, Mali, Cite du Niger. BP: 34, Bamako, Mali. Chitan_Keita@africairs.net.
authors: Chitan
authors: C
authors: Keita
authors: National Malaria Control Programme, Badalabougou, Rue 108 Porte 106, Bamako, Mali. dickoabdourhamane59@yahoo.fr.
authors: Abdourhamane
authors: A
authors: Dicko
authors: PMI Africa Indoor Residual Spraying Project, Abt Associates, 4550 Montgomery Ave, Suite 800 North, Bethesda, MD, 20814, USA. Dereje_Dengela@abtassoc.com.
authors: Dereje
authors: D
authors: Dengela
authors: PMI Africa Indoor Residual Spraying Project, Abt Associates, 4550 Montgomery Ave, Suite 800 North, Bethesda, MD, 20814, USA. colemanjane@gmail.com.
authors: Jane
authors: J
authors: Coleman
authors: PMI Africa Indoor Residual Spraying Project, Abt Associates, 4550 Montgomery Ave, Suite 800 North, Bethesda, MD, 20814, USA. Bradford_Lucas@abtassoc.com.
authors: Bradford
authors: B
authors: Lucas
authors: President's Malaria Initiative USAID, ACI2000, Rue 243, Porte 297-BP 34, Bamako, Mali. jmihigo@usaid.gov.
authors: Jules
authors: J
authors: Mihigo
authors: President's Malaria Initiative USAID, ACI2000, Rue 243, Porte 297-BP 34, Bamako, Mali. asadou@usaid.gov.
authors: Aboubacar
authors: A
authors: Sadou
authors: President's Malaria Initiative USAID, 1300 Pennsylvania Avenue NW, Washington DC, USA. abelemvire@usaid.gov.
authors: Allison
authors: A
authors: Belemvire
authors: President's Malaria Initiative USAID, 1300 Pennsylvania Avenue NW, Washington DC, USA. kgeorge@usaid.gov.
authors: Kristen
authors: K
authors: George
authors: President's Malaria Initiative USAID, 1300 Pennsylvania Avenue NW, Washington DC, USA. cfornadel@usaid.gov.
authors: Christen
authors: C
authors: Fornadel
authors: Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. rfb1@cdc.gov.
authors: Raymond
authors: R
authors: Beach
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D001681:Biological Assay; D002219:Carbamates / Q000494:pharmacology; D003634:DDT / Q000494:pharmacology; D005260:Female; D005838:Genotype; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology; D007303:Insect Vectors / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D007305:Insecticide Resistance / Q000235:genetics / Q000502:physiology; D007306:Insecticides / Q000494:pharmacology*; D008302:Mali; D009154:Mutation; D010755:Organophosphates / Q000494:pharmacology; D062486:Public Health Surveillance; D011722:Pyrethrins / Q000494:pharmacology
chemical_list: D002219:Carbamates; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; D010755:Organophosphates; D011722:Pyrethrins; D003634:DDT