title: Selection for chloroquine-sensitive Plasmodium falciparum by wild Anopheles arabiensis in Southern Zambia.
abstract: BACKGROUND
  The emergence of parasite drug resistance, especially Plasmodium falciparum, persists as a major obstacle for malaria control and elimination. To develop effective public health containment strategies, a clear understanding of factors that govern the emergence and spread of resistant parasites in the field is important. The current study documents selection for chloroquine-sensitive malaria parasites by wild Anopheles arabiensis in southern Zambia.
  
  
  METHODS
  In a 2,000-sq km region, mosquitoes were collected from human sleeping rooms using pyrethrum spray catches during the 2006 malaria transmission season. After morphological examination and molecular confirmation, vector mosquitoes were dissected to separate head and thorax from the abdominal section, followed by PCR screening for P. falciparum infection. Human residents of all ages were tested for P. falciparum parasitaemia by microscopy and PCR. Plasmodium falciparum infections were genotyped at the chloroquine resistance-conferring amino acid codon 76 of the PfCRT gene, using PCR and restriction enzyme digestion.
  
  
  RESULTS
  In the human population there was nearly 90% prevalence of the chloroquine-resistant PfCRT K76T mutant, with no significant differences in polymorphism among smear-positive and smear-negative (submicroscopic) infections (p = 0.323, n = 128). However, infections in both abdominal and salivary gland phases of the An. arabiensis vector exhibited wild type K76-bearing parasites with up to 9X higher odds (OR (95% CI): 9 (3.7-20.2), p < 0.0005, n = 125), despite having been acquired from humans within a few weeks.
  
  
  CONCLUSIONS
  Anopheles arabiensis selects for wild-type K76-bearing P. falciparum during both abdominal and salivary gland phases of parasite development. The rapid vectorial selection, also recently seen with antifolate resistance, is evidence for parasite fitness cost in the mosquito, and may underpin regional heterogeneity in the emergence, spread and waning of drug resistance. Understanding the nature and direction of vector selection could be instrumental for rational curtailment of the spread of drug resistance in integrated malaria control and elimination programmes.
authors.affiliation: The Malaria Institute at Macha, PO Box 630166, Choma, Zambia. sungano.mharakurwa@macharesearch.org.
authors.forename: Sungano
authors.initials: S
authors.lastname: Mharakurwa
authors.forename: Mavis
authors.initials: M
authors.lastname: Sialumano
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.forename: Alan
authors.initials: A
authors.lastname: Scott
authors.forename: Philip
authors.initials: P
authors.lastname: Thuma
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D016054:DNA, Protozoan / Q000235:genetics; D005838:Genotype; D026901:Membrane Transport Proteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015800:Protozoan Proteins / Q000235:genetics*; D012641:Selection, Genetic; D015024:Zambia
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine