title: Community screening and treatment of asymptomatic carriers of Plasmodium falciparum with artemether-lumefantrine to reduce malaria disease burden: a modelling and simulation analysis.
abstract: BACKGROUND
  Asymptomatic carriers of Plasmodium falciparum serve as a reservoir of parasites for malaria transmission. Identification and treatment of asymptomatic carriers within a region may reduce the parasite reservoir and influence malaria transmission in that area.
  
  
  METHODS
  Using computer simulation, this analysis explored the impact of community screening campaigns (CSC) followed by systematic treatment of P. falciparum asymptomatic carriers (AC) with artemether-lumefantrine (AL) on disease transmission. The model created by Okell et al (originally designed to explore the impact of the introduction of treatment with artemisinin-based combination therapy on malaria endemicity) was modified to represent CSC and treatment of AC with AL, with the addition of malaria vector seasonality. The age grouping, relative distribution of age in a region, and degree of heterogeneity in disease transmission were maintained. The number and frequency of CSC and their relative timing were explored in terms of their effect on malaria incidence. A sensitivity analysis was conducted to determine the factors with the greatest impact on the model predictions.
  
  
  RESULTS
  The simulation showed that the intervention that had the largest effect was performed in an area with high endemicity (entomological inoculation rate, EIR > 200); however, the rate of infection returned to its normal level in the subsequent year, unless the intervention was repeated. In areas with low disease burden (EIR < 10), the reduction was sustained for over three years after a single intervention. Three CSC scheduled in close succession (monthly intervals) at the start of the dry season had the greatest impact on the success of the intervention.
  
  
  CONCLUSIONS
  Community screening and treatment of asymptomatic carriers with AL may reduce malaria transmission significantly. The initial level of disease intensity has the greatest impact on the potential magnitude and duration of malaria reduction. When combined with other interventions (e.g. long-lasting insecticide-treated nets, rapid diagnostic tests, prompt diagnosis and treatment, and, where appropriate, indoor residual spraying) the effect of this intervention can be sustained for many years, and it could become a tool to accelerate the reduction in transmission intensity to pre-elimination levels. Repeated interventions at least every other year may help to prolong the effect. The use of an effective diagnostic tool and a highly effective ACT, such as AL, is also vital. The modelling supports the evaluation of this approach in a prospective clinical trial to reduce the pool of infective vectors for malaria transmission in an area with marked seasonality.
authors.affiliation: Department of Pharmaceutics, University of Utah, Salt Lake City, Utah, USA. steven.kern@novartis.com
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kern
authors.forename: Alfred B
authors.initials: AB
authors.lastname: Tiono
authors.forename: Michael
authors.initials: M
authors.lastname: Makanga
authors.forename: Adama Dodji
authors.initials: AD
authors.lastname: Gbadoé
authors.forename: Zulfiqarali
authors.initials: Z
authors.lastname: Premji
authors.forename: Oumar
authors.initials: O
authors.lastname: Gaye
authors.forename: Issaka
authors.initials: I
authors.lastname: Sagara
authors.forename: David
authors.initials: D
authors.lastname: Ubben
authors.forename: Marc
authors.initials: M
authors.lastname: Cousin
authors.forename: Fiyinfolu
authors.initials: F
authors.lastname: Oladiran
authors.forename: Oliver
authors.initials: O
authors.lastname: Sander
authors.forename: Bernhards
authors.initials: B
authors.lastname: Ogutu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage*; D058070:Asymptomatic Diseases; D002648:Child; D002675:Child, Preschool; D003140:Communicable Disease Control / Q000379:methods; D003198:Computer Simulation; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage*; D005449:Fluorenes / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D015233:Models, Statistical; D010274:Parasitology / Q000379:methods*; D055815:Young Adult
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes