An unusual number of goodies in Nature this week

A special Outlook issue reviewing the challenges of malaria control:

Nature Outlook: Malaria (Open access)

The war against the malaria parasite has raged for millennia, and still claims hundreds of thousands of lives each year. Resistance is a growing issue — for both the parasite to current therapy, and the mosquito to pesticides. Past attempts to eradicate malaria have failed. What will it take to finally subdue this deadly disease?

Commentary on the ivory tower:

Global issues: Make social sciences relevant
Luk Van Langenhove

Excerpt:

The social sciences are flourishing. As of 2005, there were almost half a million professional social scientists from all fields in the world, working both inside and outside academia. According to the World Social Science Report 2010 (ref. 1), the number of social-science students worldwide has swollen by about 11% every year since 2000, up to 22 million in 2006. 

Yet this enormous resource is not contributing enough to today's global challenges, including climate change, security, sustainable development and health. These issues all have root causes in human behaviour: all require behavioural change and social innovations, as well as technological development.... 

Despite these factors, many social scientists seem reluctant to tackle such issues. And in Europe, some are up in arms over a proposal to drop a specific funding category for social-science research and to integrate it within cross-cutting topics of sustainable development. This is a shame — the community should be grasping the opportunity to raise its influence in the real world.... 

Today, the social sciences are largely focused on disciplinary problems and internal scholarly debates, rather than on topics with external impact.... 

The main solution, however, is to change the mindset of the social-science community, and what it considers to be its main goal. If I were a student now, I would throw myself at global challenges and social innovations; I hope to encourage today's young researchers to do the same.

Meta-analysis of a famous question:

Comparing the yields of organic and conventional agriculture
Verena Seufert, Navin Ramankutty & Jonathan A. Foley

Abstract: Numerous reports have emphasized the need for major changes in the global food system: agriculture must meet the twin challenge of feeding a growing population, with rising demand for meat and high-calorie diets, while simultaneously minimizing its global environmental impacts1, 2. Organic farming—a system aimed at producing food with minimal harm to ecosystems, animals or humans—is often proposed as a solution3, 4. However, critics argue that organic agriculture may have lower yields and would therefore need more land to produce the same amount of food as conventional farms, resulting in more widespread deforestation and biodiversity loss, and thus undermining the environmental benefits of organic practices5. Here we use a comprehensive meta-analysis to examine the relative yield performance of organic and conventional farming systems globally. Our analysis of available data shows that, overall, organic yields are typically lower than conventional yields. But these yield differences are highly contextual, depending on system and site characteristics, and range from 5% lower organic yields (rain-fed legumes and perennials on weak-acidic to weak-alkaline soils), 13% lower yields (when best organic practices are used), to 34% lower yields (when the conventional and organic systems are most comparable). Under certain conditions—that is, with good management practices, particular crop types and growing conditions—organic systems can thus nearly match conventional yields, whereas under others it at present cannot. To establish organic agriculture as an important tool in sustainable food production, the factors limiting organic yields need to be more fully understood, alongside assessments of the many social, environmental and economic benefits of organic farming systems.

Copyright Nature

And some interesting agent-based modeling from Nature Climate Change:

Emerging migration flows in a changing climate in dryland Africa
Dominic R. Kniveton, Christopher D. Smith & Richard Black

Fears of the movement of large numbers of people as a result of changes in the environment were first voiced in the 1980s (ref. 1). Nearly thirty years later the numbers likely to migrate as a result of the impacts of climate change are still, at best, guesswork2. Owing to the high prevalence of rainfed agriculture, many livelihoods in sub-Saharan African drylands are particularly vulnerable to changes in climate. One commonly adopted response strategy used by populations to deal with the resulting livelihood stress is migration. Here, we use an agent-based model developed around the theory of planned behaviour to explore how climate and demographic change, defined by the ENSEMBLES project3 and the United Nations Statistics Division of the Department of Economic and Social Affairs4, combine to influence migration within and from Burkina Faso. The emergent migration patterns modelled support framing the nexus of climate change and migration as a complex adaptive system5. Using this conceptual framework, we show that the extent of climate-change-related migration is likely to be highly nonlinear and the extent of this nonlinearity is dependent on population growth; therefore supporting migration policy interventions based on both demographic and climate change adaptation.

New tool for interfering with malaria transmission

Geoff Johnston, a doctoral candidate at Columbia's PhD in Sustainable Development, is on the team behind this recent study in PNAS.  He's promised us a non-technical summary soon.

Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue

Sophie H. Adjalleya, Geoffrey L. Johnston, Tao Li, Richard T. Eastman, Eric H. Ekland, Abraham G. Eappen, Adam Richman, B. Kim Lee Sim, Marcus C. S. Lee, Stephen L. Hoffman, and David A. Fidock

Abstract: Clinical studies and mathematical models predict that, to achieve malaria elimination, combination therapies will need to incorporate drugs that block the transmission of Plasmodium falciparum sexual stage parasites to mosquito vectors. Efforts to measure the activity of existing antimalarials on intraerythrocytic sexual stage gametocytes and identify transmission-blocking agents have, until now, been hindered by a lack of quantitative assays. Here, we report an experimental system using P. falciparum lines that stably express gametocyte-specific GFP-luciferase reporters, which enable the assessment of dose- and time-dependent drug action on gametocyte maturation and transmission. These studies reveal activity of the first-line antimalarial dihydroartemisinin and the partner drugs lumefantrine and pyronaridine against early gametocyte stages, along with moderate inhibition of mature gametocyte transmission to Anopheles mosquitoes. The other partner agents monodesethyl-amodiaquine and piperaquine showed activity only against immature gametocytes. Our data also identify methylene blue as a potent inhibitor of gametocyte development across all stages. This thiazine dye almost fully abolishes P. falciparum transmission to mosquitoes at concentrations readily achievable in humans, highlighting the potential of this chemical class to reduce the spread of malaria.

From the author summary:

The scale of the malaria epidemic remains vast, causing up to 225 million symptomatic infections and ∼780,000 deaths each year, primarily in sub-Saharan Africa. Despite this sobering backdrop, there are encouraging signs that treating infected individuals with antimalarial therapies and combating the Anopheles mosquito vector with insecticides can substantially reduce the burden of disease. First-line therapies rely on pairing potent derivatives of the Chinese plant extract artemisinin with longer-lasting partner drugs in regimens referred to as artemisinin-based combination therapies. Clinical reports and mathematical models indicate that additional reductions in disease incidence will require treatments that not only cure patients but also decrease the transmission of malarial parasites to Anopheles mosquitoes (1). Here, we have investigated the ability of various antimalarial agents to inhibit transmission. This work reveals that methylene blue (MB), the first synthetic compound ever used in clinical therapy (2), has potent transmission-blocking activity superior to current first-line therapies. 

Interruption of transmission can be achieved with drugs that inhibit the development of parasite sexual forms, termed gametocytes, within red blood cells. In the case of the most lethal human malaria pathogen, Plasmodium falciparum, these gametocytes progress through five developmental stages over 10–12 d before becoming infectious to mosquitoes (Fig. P1A). Prior studies have found that some drugs that target the disease-causing asexual blood stages also inhibit early stage gametocytes (3). However, identifying compounds that inhibit the metabolically less active mature stages has proven considerably more difficult, in part because of a lack of robust experimental tools. To address this concern, we have developed recombinant parasite lines and analytical methods that enable precise measurements of drug action against gametocytes as they mature and attain infectivity. 

To investigate the abilities of known antimalarials to affect gametocyte viability at different stages, we genetically modified P. falciparum parasite lines to express GFP-luciferase reporters from gene promoters known to be active in early, mid, or late stage gametocytes. The production of gametocytes was triggered by starvation-induced stress, and their subsequent development and gametocyte maturation were monitored by quantifying luciferase activity. Measurements of the rate of action of antimalarial compounds, tested at different doses in vitro, revealed the remarkable potency of the thiazine dye MB against all developmental stages (Fig. P1A). Subsequent experiments revealed that MB almost fully blocked transmission of P. falciparum gametocytes to Anopheles mosquitoes (Fig. P1B), reducing parasite infectivity by 78–100%. The small proportion of mosquitoes that were infected had a >98% reduction in the numbers of parasites developing in the midgut. Most of the effect of MB on parasite transmission can be attributed to its potent activity against mature stage V gametocytes. Parallel studies also observed a potent effect with dihydroartemisinin, the active metabolite of artemisinin compounds, with inhibition occurring primarily against early stage gametocytes. Comparable activity against early stages was observed with key partner drugs, including amodiaquine and lumefantrine (4). 

The experimental system that we developed for these studies will enable high-throughput screening to identify additional transmission-blocking compounds. Our study also provides experimental tools to further probe gametocyte biology, including studies on the cellular processes and molecular components that dictate the formation of gametocytes and promote transmission (5). A renewed emphasis on this phase of the malarial parasite life cycle, using reporter systems such as the one described here, promises to further aid expanding efforts to roll back malaria.

Evidence of a link between migration and malaria

Agricultural Policy, Migration, and Malaria in the 1930s United States

Alan Barreca, Price V. Fishback, and Shawn Kantor 

Abstract: The Agricultural Adjustment Act (AAA) caused a population shift in the United States in the 1930s. Evaluating the effects of the AAA on the incidence of malaria can therefore offer important lessons regarding the broader consequences of demographic changes. Using a quasi-first difference model and a robust set of controls, we find a negative association between AAA expenditures and malaria death rates at the county level. Further, we find the AAA caused relatively low-income groups to migrate from counties with high-risk malaria ecologies. These results suggest that the AAA-induced migration played an important role in the reduction of malaria.