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      Assessment of acceptability and ease of use of atovaquone/proguanil medication in subjects undergoing malaria prophylaxis

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          International travelers from non-endemic areas are at high risk of contracting malaria due to their lack of immunity. Prevention is therefore of outmost importance and is achieved through effective and safe chemoprophylaxis, which reduces the risk of fatal disease. Among the various antimalarial drugs available, the synergistic combination of atovaquone and proguanil (A/P) (Malarone ®; Glaxo-SmithKline) has proven a valuable option in terms of effective protection against chloroquine and multi-drug resistant falciparum malaria, safety, tolerability, and ease of use, thus favoring compliance. The purpose of the present study was to assess acceptability and ease of use of A/P chemoprophylaxis in a population of employees of the oil industry bound to malarious areas. Particular attention was paid to treatment adherence.


          A survey was conducted on a sample of 700 employees on A/P chemoprophylaxis. Demographic data and specific information on A/P treatment were collected by means of a 16-item questionnaire administered immediately before departure. All questionnaires returned were then entered into a database and statistically analyzed.


          Both habitual and first-time travelers showed good adherence to A/P chemoprophylactic regimen. In general, only few adverse side-effects were reported, none of which were serious. Travelers with previous experience of other antimalarials stated A/P prophylaxis had proven advantageous due to fewer adverse reactions, better condition of administration, and better sense of protection compared with other available treatments.

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          Most cited references 22

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          Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study.

          To compare the tolerability of malaria chemoprophylaxis regimens in non-immune travellers. Randomised, double blind, study with placebo run-in phase. Travel clinics in Switzerland, Germany, and Israel. Proportion of participants in each treatment arm with subjectively moderate or severe adverse events. 623 non-immune travellers to sub-Saharan Africa: 153 each received either doxycycline, mefloquine, or the fixed combination chloroquine and proguanil, and 164 received the fixed combination atovaquone and proguanil. A high proportion of patients reported adverse events, even in the initial placebo group. No events were serious. The chloroquine and proguanil arm had the highest proportion of mild to moderate adverse events (69/153; 45%, 95% confidence interval 37% to 53%), followed by mefloquine (64/153; 42%, 34% to 50%), doxycycline (51/153; 33%, 26% to 41%), and atovaquone and proguanil (53/164; 32%, 25% to 40%) (P = 0.048 for all). The mefloquine and combined chloroquine and proguanil arms had the highest proportion of more severe events (n = 19; 12%, 7% to 18% and n = 16; 11%, 6% to 15%, respectively), whereas the combined atovaquone and proguanil and doxycycline arms had the lowest (n = 11; 7%, 2% to 11% and n = 9; 6%, 2% to 10%, respectively: P = 0.137 for all). The mefloquine arm had the highest proportion of moderate to severe neuropsychological adverse events, particularly in women (n = 56; 37%, 29% to 44% versus chloroquine and proguanil, n = 46; 30%, 23% to 37%; doxycycline, n = 36; 24%, 17% to 30%; and atovaquone and proguanil, n = 32; 20%, 13% to 26%: P = 0.003 for all). The highest proportion of moderate or severe skin problems were reported in the chloroquine and proguanil arm (n = 12; 8%, 4% to 13% versus doxycycline, n = 5; 3%, 1% to 6%; atovaquone and proguanil, n = 4; 2%, 0% to 5%; mefloquine, n = 2; 1%, 0% to 3%: P = 0.013). Combined atovaquone and proguanil and doxycyline are well tolerated antimalarial drugs. Broader experience with both agents is needed to accumulate reports of rare adverse events.
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            Imported malaria (1985-95): trends and perspectives.

            Malaria is frequently imported into nonendemic industrialized areas. In this study we collated data on the reported malaria cases in industrialized countries during the period 1985-95, with the object of identifying trends and promising strategies. The main outcome measures were incidence, case-fatality rates (CFRs), and attack rates in tourists returning from Kenya. Our survey showed gross underreporting and marked heterogeneity in the type and availability of national data. The total incidence or reported numbers of malaria infections in Europe increased from 6840 in 1985 to 7244 in 1995, with a peak of 8438 in 1989. The principal importing countries were France, Germany, Italy, and the United Kingdom. In the former USSR, the reported annual incidence dropped from 1145 in 1989 to 356 in 1990 after cessation of activities in Afghanistan. Among the imported species of malaria parasite, Plasmodium falciparum was identified in an increasing proportion, the CFR ranging from 0% to 3.6%, with consistently high rates in Germany. The attack rates among travellers to Kenya in 1990-95 were high, ranging from 18 to 207 per 100,000 travellers. Our findings indicate that in industrialized countries malaria is associated with a high CFR and remains a public health problem. Irregular surveillance and lack of homogeneity in the collected data hinder the assessment of incidences, risk groups, and the efficacy of chemoprophylaxis.
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              Atovaquone and proguanil for Plasmodium falciparum malaria.

              The increasing spread of multidrug-resistant Plasmodium falciparum malaria emphasises the urgent need for alternative treatment regimens. The objective of the study was to establish the efficacy of a novel drug combination. We compared a combination of atovaquone and proguanil with amodiaquine in the treatment of acute uncomplicated P falciparum malaria in Lambaréné, Gabon. 142 adults were randomly allocated either a combination treatment of atovaquone 1000 mg daily and proguanil 400 mg daily for 3 days or treatment with amodiaquine 600 mg on admission, 600 mg 24 h later, and 300 mg after a further 24 h. Symptoms and clinical signs were recorded and giemsa-stained thick blood smears were done every 12 h until patients had been symptom-free and aparasitaemic for 24 h. 126 patients were followed up for 28 days or until recrudescence. In the atovaquone plus proguanil group 62 (87%) of 71 patients were cured and only one had recrudescent infection. By contrast, the cure rate was significantly lower (p=0.022) with amodiaquine (51 [72%] of 71; there were 12 recrudescences in the amodiaquine group). Eight patients in each group were lost to follow-up. Patients treated with atovaquone plus proguanil complained of nausea (33%) and vomiting (29%), and the most commonly reported adverse effects of amodiaquine were pruritus (43%) and insomnia (27%). Atovaquone and proguanil was a highly effective and safe drug combination in patients with acute uncomplicated P falciparum malaria in Gabon.

                Author and article information

                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                October 2008
                October 2008
                : 4
                : 5
                : 1105-1110
                [1 ]Saipem Medical Dept. San Donato Milanese, Italy;
                [2 ]S.A.V.E. Studi Analisi Valutazioni Economiche, Milano, Italy
                Author notes
                Correspondence: Giorgio L Colombo, S.A.V.E. Studi Analisi Valutazioni Economiche, Milano, Italy, Tel +39 2 4851 9230, Fax +39 2 4819 8430, Email giorgio.colombo@ 123456savestudi.it
                © 2008 Dove Medical Press Limited. All rights reserved
                Original Research


                malaria prophylaxis, malarone, compliance, prevention, atovaquone and proguanil


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