title: A sub-microscopic gametocyte reservoir can sustain malaria transmission.
abstract: BACKGROUND
  Novel diagnostic tools, including PCR and high field gradient magnetic fractionation (HFGMF), have improved detection of asexual Plasmodium falciparum parasites and especially infectious gametocytes in human blood. These techniques indicate a significant number of people carry gametocyte densities that fall below the conventional threshold of detection achieved by standard light microscopy (LM).
  
  
  RESULTS
  To determine how low-level gametocytemia may affect transmission in present large-scale efforts for P. falciparum control in endemic areas, we developed a refinement of the classical Ross-Macdonald model of malaria transmission by introducing multiple infective compartments to model the potential impact of highly prevalent, low gametocytaemic reservoirs in the population. Models were calibrated using field-based data and several numerical experiments were conducted to assess the effect of high and low gametocytemia on P. falciparum transmission and control. Special consideration was given to the impact of long-lasting insecticide-treated bed nets (LLIN), presently considered the most efficient way to prevent transmission, and particularly LLIN coverage similar to goals targeted by the Roll Back Malaria and Global Fund malaria control campaigns. Our analyses indicate that models which include only moderate-to-high gametocytemia (detectable by LM) predict finite eradication times after LLIN introduction. Models that include a low gametocytemia reservoir (requiring PCR or HFGMF detection) predict much more stable, persistent transmission. Our modeled outcomes result in significantly different estimates for the level and duration of control needed to achieve malaria elimination if submicroscopic gametocytes are included.
  
  
  CONCLUSIONS
  It will be very important to complement current methods of surveillance with enhanced diagnostic techniques to detect asexual parasites and gametocytes to more accurately plan, monitor and guide malaria control programs aimed at eliminating malaria.
authors.affiliation: School of Physics, The University of Western Australia, Crawley, Western Australia, Australia. stephan.karl@physics.uwa.edu.au
authors.forename: Stephan
authors.initials: S
authors.lastname: Karl
authors.forename: David
authors.initials: D
authors.lastname: Gurarie
authors.forename: Peter A
authors.initials: PA
authors.lastname: Zimmerman
authors.forename: Charles H
authors.initials: CH
authors.lastname: King
authors.forename: Tim G
authors.initials: TG
authors.lastname: St Pierre
authors.forename: Timothy M E
authors.initials: TM
authors.lastname: Davis
mesh_terms: D050936:Basic Reproduction Number; D002138:Calibration; D004197:Disease Reservoirs / Q000469:parasitology*; D005854:Germ Cells / Q000166:cytology*; D006801:Humans; D057148:Insecticide-Treated Bednets; D008288:Malaria / Q000517:prevention & control / Q000635:transmission*; D008954:Models, Biological; D009032:Mosquito Control