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Interactive data visualizations of antibiotic use and resistance in North America and Europe
The National Institutes of Health (NIH), a part of the US Department of Health and Human Services and the country’s medical research agency, is the world’s largest funder for medical research. The NIH website states that more than 80% of the agency’s budget is used to cover research costs at over 2,500 universities and research institutions.
The feasibility of eliminating malaria differs among countries because of differences in the technical challenges, measured in terms of malaria endemicity and importation rate, and operational capabilities, measured in terms of government stability and effectiveness, quality and development of health systems, and factors associated with the population at risk. The forty circles graphically represent a relative ranking of operational feasibility for eliminating P. falciparum malaria.
In 2012, there were an estimated 207 million cases of malaria and 627,000 deaths caused by malaria worldwide, according to the WHO. While malaria deaths have been greatly reduced in recent years, it is imperative that governments and global health organizations continue investing in malaria research to ensure consistent progress in fighting the disease.
How does heterogeneous transmission affect the spread of antimalarial drug resistance?
In malarious regions, individuals are bitten by infectious mosquitoes regularly. Continuous re-exposure often leads to simultaneous infection with multiple genetically distinct malaria parasites. These parasites compete within the host, which can affect the epidemiological dynamics of the disease, particularly when drug-resistant and drug-sensitive parasites compete. This is exacerbated by heterogeneous transmission, which results in certain members of the community having significantly more within-host competition than others.
By including within-host competition and heterogeneous transmission in our model, we were able to show that heterogeneous transmission slows the rate at which resistance becomes established. This is largely due to drug-susceptible strains out competing resistant strains within the host. However, once resistance in the community is established, heterogeneous transmission speeds the spread of resistance.
Our model has shown that understanding how heterogeneous transmission interacts with within-host competition is important for understanding the emergence and spread of drug resistance. Our findings should encourage additional research into within-host competition, while our model could be extended to include other important components of antimalarial drug resistance such as immunity.
This post was written in collaboration with CDDEP researcher Suraj Pant.
Below is a press release issued by the Johns Hopkins Bloomberg School of Public Health. Among the authors of the article "The Stability of Malaria Elimination," published February 22 in Science, are CDDEP director Ramanan Laxminarayan and senior fellow David Smith.
This article examines what is known about how resistance to antimalarial drugs emerges and spreads, and reviews various strategies for controlling the spread of resistance.
This paper is a literature review, and as such there are no new findings to report. However, the author concludes that "the emergence of an artemisinin-resistant phenotype threatens one of the key components of elimination and eradication plans, and new control strategies are ugently needed." He also notes that devising these strategies will require "a better understanding of how drug resistance emerges and spreads."
Artemisinin-based therapies are currently the most effective treatment for malaria. If these drugs were to be lost to resistance, which already appears to be emerging in Southeast Asia, the results could be globally catastrophic.
The emergence of resistance to former first-line antimalarial drugs has been an unmitigated disaster. In recent years, artemisinin class drugs have become standard and they are considered an essential tool for helping to eradicate the disease. However, their ability to reduce morbidity and mortality and to slow transmission requires the maintenance of effectiveness. Recently, an artemisinin delayed-clearance phenotype was described. This is believed to be the precursor to resistance and threatens local elimination and global eradication plans. Understanding how resistance emerges and spreads is important for developing strategies to contain its spread. Resistance is the result of two processes: (i) drug selection of resistant parasites; and (ii) the spread of resistance. In this review, we examine the factors that lead to both drug selection and the spread of resistance. We then examine strategies for controlling the spread of resistance, pointing out the complexities and deficiencies in predicting how resistance will spread.
Carlos Guerra's research interests have focused mainly on global malaria epidemiology. He worked as a full time researcher for the Malaria Atlas Project (MAP) from 2005 to 2011. During this period he assembled medical intelligence and malaria survey data to provide evidence-based maps on the distribution of malaria risk, human population, disease burdens, mosquito vectors, inherited blood disorders and malaria financing and control worldwide. He is still a collaborator of MAP.
What lessons can be taken away from the Affordable Medicines Facility-malaria pilot?
After examining the results of a 2-year pilot in seven African countries (Ghana, Kenya, Madagascar, Niger, Nigeria, and Tanzania, including Zanzibar and Uganda), the authors drew four main conclusions that should be taken into account in subsequent phases of AMFm:
In mid-November 2012, the board of directors of Global Fund to Fight AIDS, Tuberculosis, and Malaria will decide whether to continue, modify, or terminate AMFm. This decision has broad implications for the availability and affordability of effective malaria medications going forward. As the piece concludes:
"Termination of AMFm will create instability in artemisinin production, will reduce access to affordable ACTs, and will be seen as abandonment - both by the many people who depend on AMGm and by the ACT producers. It will cause the kind of reaction that will detract from efforts to reduce deaths from malaria, to engage the private sector in providing community-based health care in poor countries, and to build credible health diplomacy."
In 2001, the World Health Organization (WHO) recommended that countries use artemisinin-based combination therapies (ACTs) to treat malaria patients (1), as continued use of artemisinin monotherapies and substandard drugs had the potential to lead to widespread resistance to artemisinin, the most effective drug for malaria. But ACTs were unaffordable for most people in malaria-endemic countries, particularly in the private for-profit sector where most people seek treatment. Artemisinin monotherapies and the threat of resistance remain a problem. Resistance has now emerged in Cambodia and is spreading to Myanmar and Vietnam (2). Despite WHO's efforts, monotherapies are produced by 37 pharmaceutical companies and marketed in 29 countries (3). Although resistance to artemisinin had not been detected at the time of the Institute of Medicine (IOM) report in 2004 (4), an IOM committee proposed a global subsidy high in the distribution chain, both to make ACTs inexpensive and to displace artemisinin monotherapy and other ineffective drugs.