Randomized, Placebo-Controlled Trial of Atovaquone/Proguanil for the Prevention of Plasmodium falciparum or Plasmodium vivax Malaria among Migrants to Papua, Indonesia

George Washington University, Washington, Washington, D.C., United States
Clinical Infectious Diseases (Impact Factor: 8.89). 10/2002; 35(7):825-33. DOI: 10.1086/342578
Source: PubMed


The increasing prevalence of resistance to antimalarial drugs reduces options for malaria prophylaxis. Atovaquone/proguanil
(Malarone; GlaxoSmithKline) has been >95% effective in preventing Plasmodium falciparum malaria in lifelong residents of areas of holoendemicity, but data from persons without clinical immunity or who are at risk
for Plasmodium vivax malaria have not been described. We conducted a randomized, double-blinded study involving 297 people from areas of nonendemicity
in Indonesia who migrated to Papua (where malaria is endemic) ⩽26 months before the study period. Subjects received prophylaxis
with 1 Malarone tablet (250 mg of atovaquone and 100 mg of proguanil hydrochloride; n = 148) or placebo (n = 149) per day for 20 weeks. Hematologic and clinical chemistry values did not change significantly. The protective efficacy
of atovaquone/proguanil was 84% (95% confidence interval [CI], 44%–95%) for P. vivax malaria, 96% (95% CI, 72%–99%) for P. falciparum malaria, and 93% (95% CI, 77%–98%) overall. Atovaquone/proguanil was well tolerated, safe, and effective for the prevention
of drug-resistant P. vivax and P. falciparum malaria in individuals without prior malaria exposure who migrated to Papua, Indonesia.

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Available from: J. Kevin Baird, Dec 05, 2015
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    • "The infrequent use of chemoprophylaxis is a concern on a global scale. Although anti-malarial drug resistances are emerging in endemic countries, chemoprophylaxis is still effective and selection of a good regimen, along with barrier and repellent precautions, is key to decreasing the risk of acquiring malaria [39]. The rate of correct chemoprophylaxis completion among cases in this study population is similar to that found in previous studies, which ranges from 3-15% [19,31,38]. "
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    ABSTRACT: Increasing international travel and migration is producing changes in trends in infectious diseases, especially in children from many European cities. The objective of this study was to describe the epidemiology and determine the trends of imported malaria in patients under 20 years old in the city of Barcelona, Spain, during an 18-year period. The study included malaria cases that were laboratory confirmed and reported to the malaria register at the Public Health Agency of Barcelona from 1990 to 2008, residing in Barcelona and less than 20 years old. Patients were classified as natives (born in Spain) or immigrants. Differences in the distribution of demographic, clinical characteristics, and incidence per 100,000 person-year evolution were analysed. Natives and immigrants were compared by logistic regression by calculating the odds ratio (OR) with a 95% confidence interval (CI) and Chi-square for a linear trend (p<0.05). Of the total 174 cases, 143 (82.1%) were immigrants, 100 (57.5%) were female, 121 (69.5%) Plasmodium falciparum, and 108 (62.1%) were visiting friends and relatives (VFR) as the reason for travel. Among the immigrants, 99 (67.8%) were from Equatorial Guinea. Immigrant cases more frequently travelled to Africa than natives (p=0.02). The factors associated with imported malaria among immigrant residents was travelling for VFR (OR: 6.2 CI 1.9-20.2) and age 15-19 (OR: 3.7 CI 1-13.3). The incidence increased from 1990 to 1999 (p<0.001) and decreased from 2000 to 2008 (p=0.01), although the global linear trend was not statistically significant (p=0.41). The fatality rate was 0.5%. The majority of cases of malaria in population less than 20 years in Barcelona were immigrants, travelling to Africa for VFR and Plasmodium falciparum was most frequently detected. The trend analysis of the entire study period did not show a statistically significant decline. It is recommended to be aware of malaria, especially among children of immigrants who travel to their parent's home country for VFR. Better access to pre travel advice should be provided.
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    • "Lesser Sundas: (Baird et al., 1990; Barodji et al., 1994, 1996; Carney et al., 1975b; Dachlan et al., 2005; Fryauff et al., 1997b; Gundelfinger et al., 1975; Hoffman et al., 1984; Jalloh et al., 2004; Jodjana and Eblen, 1997; Joesoef and Dennis, 1980; Jones et al., 1993; Marwoto and Martono, 1991; Marwoto and Purnomo, 1992; Mucide et al., 1998; Nalim et al., 1997; Ompusunggu et al., 2006; Smrkovski et al., 1983; Susanto et al., 2005; Syafruddin et al., 2006, 2009; Tjitra, 2001). Papua: (Andersen et al., 1997; Anthony et al., 1992; Baird, 1998; Baird et al., 1993, 1997b; Bangs et al., 1992; Barcus et al., 2003; Cross et al., 1977; De Rook, 1929; Dimpudus et al., 1981; Fryauff et al., 1997d, 2000; Hutapea, 1979; Kariadi, 1936; Karyana et al., 2008; Lee et al., 1980; Ling et al., 2002; Metselaar, 1956a, 1959; Meuwissen, 1961; Mooij, 1932; Pribadi et al., 1998; Purnomo et al., 1999; Sunaryo, 2006; Tjitra, 2001; Van der Kaay et al., 1973; Verdrager et al., 1976b; Voors, 1955). "
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    ABSTRACT: Approximately 230 million people live in Indonesia. The country is also home to over 20 anopheline vectors of malaria which transmit all four of the species of Plasmodium that routinely infect humans. A complex mosaic of risk of infection across this 5000-km-long archipelago of thousands of islands and distinctive habitats seriously challenges efforts to control malaria. Social, economic and political dimensions contribute to these complexities. This chapter examines malaria and its control in Indonesia, from the earliest efforts by malariologists of the colonial Netherlands East Indies, through the Global Malaria Eradication Campaign of the 1950s, the tumult following the coup d'état of 1965, the global resurgence of malaria through the 1980s and 1990s and finally through to the decentralization of government authority following the fall of the authoritarian Soeharto regime in 1998. We detail important methods of control and their impact in the context of the political systems that supported them. We examine prospects for malaria control in contemporary decentralized and democratized Indonesia with multidrug-resistant malaria and greatly diminished capacities for integrated malaria control management programs.
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    • "Four randomized placebo-controlled trials reported a 97-100% efficacy of a fixed combination of atovaquone (250 mg) and proguanil (100 mg) in preventing P. falciparum malaria in semi-immune long-term residents in high malaria endemic areas of Africa. Atovaquone-proguanil has also demonstrated causal prophylactic action on the tissue forms of P.falciparum [59] while the protective efficacy against P. vivax has been shown to be moderate (84%) [58,59]. In a randomised study on healthy volunteers under aircraft cabin pressure conditions, atovaqone/proguanil has caused mild side effects such as nausea, vomiting, abdominal pain and stomatitis, but it did not cause insomnia or impaired ability to process information or impaired degree of attention and vigilance [58,61]. "
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    ABSTRACT: The flow of international travellers to and from malaria-endemic areas, especially Africa, has increased in recent years. Apart from the very high morbidity and mortality burden imposed on malaria-endemic areas, imported malaria is the main cause of fever possibly causing severe disease and death in travellers coming from tropical and subtropical areas, particularly Sub-Saharan Africa. The importance of behavioural preventive measures (bed nets, repellents, etc.), adequate chemoprophylaxis and, in selected circumstances, stand-by emergency treatment may not be overemphasized. However, no prophylactic regimen may offer complete protection. Expert advice is needed to tailor prophylactic advice according to traveller (age, baseline clinical conditions, etc.) and travel (destination, season, etc.) characteristics in order to reduce malaria risk.
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