Knowledge, attitudes, and practices regarding antimalarial chemoprophylaxis in U.S. Peace Corps Volunteers--Africa, 2013.

Long-term travelers to areas where malaria is endemic are at risk for this potentially fatal disease; however, malaria can be prevented through the use of insecticide-treated bednets, mosquito repellents, and chemoprophylaxis. Three options for chemoprophylaxis are available in the Africa region: mefloquine, doxycycline, and atovaquone-proguanil. These options differ by dosing regimen, cost, and side effect profile. Long-term adverse effects of these drugs have been reported rarely.

Malaria chemoprophylaxis: what do the travelers choose, and how does pretravel consultation influence their final decision.

Three different drugs (mefloquine, atovaquone/proguanil, doxycycline) are recommended for malaria chemoprophylaxis, each with approximately the same efficacy but various adverse event profiles, regimens, and prices. We investigated which medication the travelers would have chosen on the basis of written evidence-based information and the impact that pretravel consultation had on their decision. A prospective study was performed in a travel clinic and private practice, and 1073 travelers were included; 45% chose mefloquine (Lariam or Mephaquine), 21% atovaquone/proguanil (Malarone), 18% doxycycline (Supracycline), 5% "no prophylaxis," and 11% "do not know." Lariam was principally chosen because of prior experience (38%), Mephaquine because of low price (34%), and doxycycline and Malarone because of the profile of adverse events (55% and 43%, respectively). Based on objective written information, travelers most frequently chose mefloquine for chemoprophylaxis. This suggests that evidence-based information weighs more heavily than negative publicity. Taking into account the perspective of the user should improve appropriateness of the pretravel advice.

Atovaquone + proguanil: new preparation. Second-line antimalarial combination.

(1) Quinine, halofantrine and mefloquine are effective treatments for most cases of uncomplicated Plasmodium falciparum malaria. (2) The choice of drug for prevention of P. falciparum malaria in highly endemic regions depends on the risk of chloroquine resistance, and possibly mefloquine resistance. The reference treatments are the chloroquine + proguanil combination, and mefloquine. (3) Marketing authorisation has been granted in France for the atovaquone + proguanil combination, in curative and preventive treatment of P. falciparum malaria. (4) The efficacy of the atovaquone + proguanil combination in uncomplicated malaria is similar to that of other treatments. Some strains of malaria seem to have reduced sensitivity. (5) The atovaquone + proguanil combination is also effective as prophylaxis, but there are no clinical trials showing whether it is equivalent to or better than other preventive treatments in non immune travellers. (6) According to the French licensing terms, atovaquone + proguanil prophylaxis can be stopped 7 days after leaving an endemic area, rather than 3-4 weeks with other drugs. This recommendation is based on weak evidence: mainly on theoretical arguments and on the absence of clinical malaria in some patients with evidence of P. falciparum infection. (7) The atovaquone + proguanil combination is less effective against other Plasmodium species (P. malariae, P. ovale and P. vivax). Chloroquine remains the reference treatment for these forms of malaria, which do not carry a risk of serious complications. (8) There were few adverse events in people taking the atovaquone + proguanil combination during clinical trials. During curative treatment, this combination caused more nausea and vomiting than reference treatments, while, in the prophylactic setting, it had slightly fewer adverse effects than the chloroquine + proguanil combination or mefloquine alone. But the drop out rate was not significantly different between treatment groups. (9) Atovaquone should be taken with food, to improve absorption. (10) The atovaquone + proguanil combination is expensive and is not refunded in France. In contrast, curative treatment with quinine is cheap, and is fully refunded. (11) Mefloquine and quinine remain the treatments of choice for uncomplicated malaria where there is chloroquine resistance. The atovaquone + proguanil combination is useful if mefloquine and quinine are contraindicated; unlike halofantrine, this combination does not carry the risk of serious drug interactions. In the prophylactic setting, the lack of experience with atovaquone means it should only be used as a second line option, after mefloquine, for short-term prophylaxis in areas with a high prevalence of chloroquine resistance.

Lariam's legacy.

The most-prescribed malaria drug could produce psychiatric side effects in more than one-quarter of all travelers who take it.

Chlorproguanil-dapsone (LAPDAP) for uncomplicated falciparum malaria.

The synergistic antifolate combination of chlorproguanil with dapsone (CPG-DDS; LAPDAP) is being developed by a public-private partnership as a low-cost treatment for uncomplicated falciparum malaria. LAPDAP is rapidly eliminated from the body, giving it low selection pressure for drug resistance. Clinical cases with sulphadoxine-pyrimethamine (SP)-resistant infections acquired in Africa have been predicted to be responsive to LAPDAP, and clinical evidence is available to support this. A regulatory dossier is being prepared for simultaneous submission to the UK Medicines Control Agency and African licencing authorities. The team working on LAPDAP has also started to develop the triple combination of chlorproguanil-dapsone-artesunate (CDA) as a low-cost combination therapy for uncomplicated falciparum malaria. Although LAPDAP does not have regulatory approval (and development of CDA is at an early stage), the development team is keen to communicate with public health scientists to try to anticipate the policy and implementation hurdles that lie ahead. This short paper outlines the current stages that LAPDAP and CDA have reached, and sketches the anticipated public health issues.