A Second Chance to Tackle African Malaria Vector Mosquitoes that Avoid Houses and Don't Take Drugs

Sometimes history gives us a second chance by repeating itself. The timely and lucid modeling analysis presented by Phillip Eckhoff in this issue reminds us all that the challenges and opportunities faced by the malaria control community today remain remarkably similar to those of our predecessors who undertook the Global Malaria Eradication Campaign (GMEP). The anti-malarial drugs we use in 2013 are relatively new to the front lines but they are still overwhelmingly used in the same way for reactive clinical management of symptomatic cases. Long-lasting insecticidal nets (LLINs) now offer a proven alternative to indoor residual spraying (IRS) as the front-line vector control tool of the GMEP era but both approaches target mosquitoes within the same indoor environment and evidence that combining the two yields incremental benefits remains mixed. Although efficacious vaccines against malaria now exist and their expected impacts are simulated here, the protection they confer is partial and may wane as naturally acquired immunity fades and/or naturally acquired skin stage infections induce immunotolerance of pre-erythrocytic stages. Therefore, the fundamental properties, applications, and limitations of “offthe-shelf” intervention options available to control program managers today have not dramatically changed since the heyday of GMEP optimism half a century ago. And neither have the most fundamental knowledge gaps we face. The white arrows in Figure 1 crudely illustrate the impacts of intervention strategies we have reasonable experience and understanding of (suppression of high transmission with LLINs or IRS and elimination of sparse residual human parasite reservoirs with drugs), whereas the dark arrows illustrate those we urgently need to develop and learn about through trial and error (longterm resistance management, programmatic-scale vector control outdoors or at source, elimination of mosquito-to-human transmission during the dry season with vaccines, novel vector control tools, or chemoprophylaxis). The four major issues highlighted by this intricate set of simulations, using a remarkably flexible and extendable modeling architecture, are as follows. 1) We need more intervention layers of vector and parasite control to eliminate malaria from African settings than we presently have available. 2) Options for vector control outdoors or at source remain conspicuous by their absence. 3) Although recently developed vaccines narrow this gap, between the control levels we can achieve today and the elimination target we have set for ourselves, they do not fill it. 4) Parasite populations are buffered against extinction by low levels of persisting transmission during the dry season, which represents a far more manageable target for targeted intervention than peaks of transmission associated with the rainy season. Although none of these insights are entirely unprecedented, they have never before been given such explicit emphasis and integrated consideration as the obstacles we must overcome to eliminate malaria from equatorial Africa. Furthermore, the timing could not possibly be better: These predictions that dramatic reductions of transmission can be achieved in Africa parallels reality on the ground in many countries today, while at the same time, the global financial support base for national control programs is in clear and present danger. Less than 6 years have passed since the dramatic reprioritization of local, national and regional elimination, ultimately leading to worldwide eradication, as the long-term goal of the global malaria control strategy. Since then, high coverage with proven vector control methods and effective drugs has become increasingly commonplace and saves hundreds of thousands of lives annually. However, elimination of transmission from African settings remains as elusive as ever, even in settings where these historical cornerstones of malaria control have been supplemented by the most advanced malaria vaccine available. As explained using an unusually explicit and detailed model, the most effective intervention technologies available today have largely delivered on reasonable expectations but their fundamental limitations persist because the biology of malaria parasites and vectors have not changed. Unlike the GMEP generation, we have the privilege of hindsight, embraced malaria elimination and eradication goals fully informed by historical precedents, and should be encouraged that we now find ourselves at this difficult but predictable crossroads again so soon. The recent rapid gains in both coverage and impact of LLINs and IRS are massive and unprecedented but also worryingly fragile. The immediate threat of funding stagnation, or even contraction, belies an even more dangerous loss of confidence by the global public based on media emphasis of the know limitations of established control technologies that still “do what they say on the tin” but no more. So what was written in the historical fine print on the side of the tin that this article illuminates for us? What are the scientific, implementation, and stakeholder engagement issues this article raises? More to the point, how should we address them now that history has given us a second chance? First, this article outlines in great detail why layering of all available effective interventions (vector control in the form of LLINs or IRS, therapeutic drugs, and vaccines) is required to reduce transmission levels to manageable levels but is unlikely to extinguish it from many parts of sub-Saharan *Address correspondence to Gerry F. Killeen, Ifakara Health Institute, Environmental Health and Ecological Sciences Thematic Group, PO Box 53, Ifakara, Kilombero District, Morogoro Region, United Republic of Tanzania. E-mail: [email protected]