title: Comparative benefit of malaria chemoprophylaxis modelled in United Kingdom travellers.
abstract: BACKGROUND
  Chemoprophylaxis against falciparum malaria is recommended for travellers from non-endemic countries to malarious destinations, but debate continues on benefit, especially with regard to mefloquine. Quantification of benefit for travellers from the United Kingdom (UK) was modelled to assist clinical and public health decision making.
  
  
  METHODS
  The model was constructed utilising: World Tourism Organization data showing total number of arrivals from the UK in countries with moderate or high malaria risk; data from a retrospective UK Clinical Practice Research Datalink (CPRD) drug utilisation study; additional information on chemoprophylaxis, case fatality and tolerability were derived from the travel medicine literature. Chemoprophylaxis with the following agents was considered: atovaquone-proguanil (AP), chloroquine with and without proguanil (C ± P), doxycycline (Dx), mefloquine (Mq). The model was validated for the most recent year with temporally matched datasets for UK travel destinations and imported malaria (2007) against UK Health Protection Agency data on imported malaria.
  
  
  RESULTS
  The median (mean) duration of chemoprophylaxis for each agent in weeks (CPRD) was: AP 3.3 (3.5), C ± P 9 (12.1), Dx 8 (10.3), Mq 9 (12.3): the maximum duration of use of all regimens was 52 weeks. The model correctly predicted falciparum malaria deaths and gave a robust estimate of total cases--model: 5 deaths from 1118 cases; UK Health Protection Agency: 5 deaths from 1153 cases. The number needed to take chemoprophylaxis (NNP) to prevent a case of malaria considered against the 'background' reported incidence in non-users of chemoprophylaxis deemed in need of chemoprophylaxis was: C ± P 272, Dx 269, Mq 260, AP 252; the NNP to prevent a UK traveller malaria death was: C ± P 62613, Dx 61923, Mq 59973, AP 58059; increasing the 'background' rate by 50% yielded NNPs of: C ± P 176, Dx 175, Mq 171, AP 168. The impact of substituting atovaquone-proguanil for all mefloquine usage resulted in a 2.3% decrease in estimated infections. The number of travellers experiencing moderate adverse events (AE) or those requiring medical attention or drug withdrawal per case prevented is as follows: C ± P 170, Mq 146, Dx 114, AP 103.
  
  
  CONCLUSIONS
  The model correctly predicted the number of malaria deaths, providing a robust and reliable estimate of the number of imported malaria cases in the UK, and giving a measure of benefit derived from chemoprophylaxis use against the likely adverse events generated. Overall numbers needed to prevent a malaria infection are comparable among the four options and are sensitive to changes in the background infection rates. Only a limited impact on the number of infections can be expected if Mq is substituted by AP.
authors.forename: Stephen
authors.initials: S
authors.lastname: Toovey
authors.forename: Keith
authors.initials: K
authors.lastname: Nieforth
authors.forename: Patrick
authors.initials: P
authors.lastname: Smith
authors.forename: Patricia
authors.initials: P
authors.lastname: Schlagenhauf
authors.forename: Miriam
authors.initials: M
authors.lastname: Adamcova
authors.forename: Iain
authors.initials: I
authors.lastname: Tatt
authors.forename: Danitza
authors.initials: D
authors.lastname: Tomianovic
authors.forename: Gabriel
authors.initials: G
authors.lastname: Schnetzler
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D053626:Atovaquone / Q000009:adverse effects / Q000627:therapeutic use; D018890:Chemoprevention / Q000379:methods; D002738:Chloroquine / Q000009:adverse effects / Q000627:therapeutic use; D004318:Doxycycline / Q000009:adverse effects / Q000627:therapeutic use; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004363:Drug Utilization / Q000706:statistics & numerical data; D006801:Humans; D008288:Malaria / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control*; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control*; D015767:Mefloquine / Q000009:adverse effects / Q000627:therapeutic use; D015233:Models, Statistical; D002727:Proguanil / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D012306:Risk; D014195:Travel; D006113:United Kingdom
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C109496:atovaquone, proguanil drug combination; D002738:Chloroquine; D004318:Doxycycline; D002727:Proguanil; D015767:Mefloquine; D053626:Atovaquone