Comparative benefit of malaria chemoprophylaxis modelled in United Kingdom travellers

• Published in: Travel medicine and infectious disease 2014-11, Vol.12 (6), p.726-732
• Main Authors: Toovey, Stephen, Nieforth, Keith, Smith, Patrick, Schlagenhauf, Patricia, Adamcova, Miriam, Tatt, Iain, Tomianovic, Danitza, Schnetzler, Gabriel
• Format: Article
• Language: English
• Subjects: Antimalarials - therapeutic use; Atovaquone - adverse effects; Atovaquone - therapeutic use; Atovaquone-proguanil; Calendars; Chemoprevention - methods; Chloroquine; Chloroquine - adverse effects; Chloroquine - therapeutic use; Doxycycline; Doxycycline - adverse effects; Doxycycline - therapeutic use; Drug Combinations; Drug Therapy, Combination; Drug Utilization - statistics & numerical data; Fatalities; Health risks; Humans; Infections; Infectious Disease; Malaria; Malaria - epidemiology; Malaria - mortality; Malaria - prevention & control; Malaria, Falciparum - epidemiology; Malaria, Falciparum - mortality; Malaria, Falciparum - prevention & control; Mefloquine; Mefloquine - adverse effects; Mefloquine - therapeutic use; Models, Statistical; Mortality; Proguanil - adverse effects; Proguanil - therapeutic use; Prophylaxis; Public health; Retrospective Studies; Risk; Studies; Tourism; Travel; Travel medicine; United Kingdom; Vector-borne diseases
• ISSN: 1477-8939; 1873-0442
• DOI: 10.1016/j.tmaid.2014.08.005

Summary 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 lik