Despite being one of the most prevalent tropical diseases, for many years malaria was not a commercial priority for the pharmaceutical industry. However, in response to the emergence and spread of resistance to the available antimalarial drugs, there has been a renaissance in the discovery and development of new medicines to control the disease in the last few years. The persistent threat of resistance means that new molecules with novel mechanisms of action are continually required. Furthermore, the recent call for the elimination and eradication of malaria has prompted an extension of the stages of the life cycle of malaria parasites that should be targeted by new molecules. Recent advances in genome-based technologies and in in vitro screening of whole parasites have broadened the range of therapeutic targets and are accelerating the development of a new generation of treatments for both malaria control and eradication.

/pdf/new-medicines-to-improve-control-and-contribute-to-the-3q00zg9re2.pdf

New medicines to improve control and contribute to the eradication of malaria

Atovaquone is used as a fixed-dose combination with proguanil (Malarone) for treating children and adults with uncomplicated malaria or as chemoprophylaxis for preventing malaria in travellers. Indeed, in the USA, between 2009 and 2011, Malarone prescriptions accounted for 70% of all antimalarial pre-travel prescriptions. In 2013 the patent for Malarone will expire, potentially resulting in a wave of low-cost generics. Furthermore, the malaria scientific community has a number of antimalarial quinolones with a related pharmacophore to atovaquone at various stages of pre-clinical development. With this in mind, it is timely here to review the current knowledge of atovaquone, with the purpose of aiding the decision making of clinicians and drug developers involved in the future use of atovaquone generics or atovaquone derivatives.

/pdf/antimalarial-pharmacology-and-therapeutics-of-atovaquone-3uardih0iw.pdf

Antimalarial pharmacology and therapeutics of atovaquone

Despite being one of the most prevalent tropical diseases, for many years malaria was not a commercial priority for the pharmaceutical industry. However, in response to the emergence and spread of resistance to the available antimalarial drugs, there has been a renaissance in the discovery and development of new medicines to control the disease in the last few years. The persistent threat of resistance means that new molecules with novel mechanisms of action are continually required. Furthermore, the recent call for the elimination and eradication of malaria has prompted an extension of the stages of the life cycle of malaria parasites that should be targeted by new molecules. Recent advances in genome-based technologies and in vitro screening of whole parasites have broadened the range of therapeutic targets and are accelerating the development of a new generation of treatments for both malaria control and eradication.

https://wiki.epfl.ch/indoswiss/documents/doerigchristian.pdf

Malaria: targeting parasite and host cell kinomes.

Background Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases. Methods and Findings For each disease, we performed a systematic search with no restriction on date or language of publication on Medline, Web of Knowledge, Cochrane CENTRAL and SCOPUS up to December 2010 to identify systematic reviews of public health interventions. We retrieved some 3176 records of which 85 full papers were assessed and 33 included in the review. The included papers investigated the effect of public health interventions on various outcome measures. All interventions were GRADE assessed to determine the strength of evidence. In addition we developed a systematic review quality score. The interventions included environmental interventions to control vectors, chemoprophylaxis, immunization, household and community water treatment, greening cities and community advice. For most reviews, GRADE showed low quality of evidence because of poor study design and high heterogeneity. Also for some key areas such as floods, droughts and other weather extremes, there are no adequate systematic reviews of potential public health interventions. Conclusion In conclusion, we found the evidence base to be mostly weak for environmental interventions that could have the most value in a warmer world. Nevertheless, such interventions should not be dismissed. Future research on public health interventions for climate change adaptation needs to be concerned about quality in study design and should address the gap for floods, droughts and other extreme weather events that pose a risk to health.

https://ueaeprints.uea.ac.uk/42532/1/Bouzid_2013_Systematic_review_of_systematic_reviews.pdf

The effectiveness of public health interventions to reduce the health impact of climate change: a systematic review of systematic reviews.

Objectives: A systematic review and meta-analysis of the effectiveness of atovaquone–proguanil (Malarone) as a chemoprophylactic agent against malaria. Methods: The data sources searched for this study included Cochrane systematic reviews (on infectious diseases), MEDLINE and EMBASE, Web of Knowledge and Annals of Tropical Medicine. All unconfounded randomized controlled trials assessing the chemoprophylaxis against malaria with atovaquone–proguanil were included in the review. Data on study design, study sample, inclusion and exclusion criteria, allocation, blinding, primary and secondary study end points were all extracted by one reviewer and independently rechecked by the second reviewer. Results: In general, all 10 studies identified had excellent quality with total scores of � 4 using the Jadad criteria. Ten controlled trials comprising 4539 participants were included for this review. A metaanalysis of six of the ten studies found chemoprophylaxis with atovaquone–proguanil, with a prophylaxis efficacy of 95.8% (95% CI 5 91.5–97.9), to be superior to placebo. It was also considered safe and better tolerated with fewer treatment-related adverse events that could lead to premature discontinuation of prophylaxis than in controls. Comparison with alternative chemoprophylaxis also showed atovaquone–proguanil to be better tolerated with fewer treatment-related self-reported adverse events (RR 5 0.8234; 95% CI 5 0.673164–1.01) or severe adverse events (RR 5 0.6140; 95% CI 5 0.420055– 0.8975). Atovaquone–proguanil is well tolerated with no difference in non-compliance with placebo (RR 5 0.8804; 95% CI 5 0.6964–1.113; I 2 5 31.4%). Conclusions: Evidence from this review shows that atovaquone–proguanil is highly efficacious as a prophylactic agent against malaria infection and is very well tolerated compared with other antimalarial agents.

/pdf/a-systematic-review-and-meta-analysis-of-the-effectiveness-2hc61go127.pdf

A systematic review and meta-analysis of the effectiveness and safety of atovaquone–proguanil (Malarone) for chemoprophylaxis against malaria

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A systematic review and meta-analysis of the effectiveness and safety of atovaquone–proguanil (Malarone) for chemoprophylaxis against malaria