At the turn of the last century, the call to action to bring to bear tools such as insecticide-treated bed nets, malaria rapid diagnostic tests and artemisinin-based combination therapies, was heard. Governments, foundations, non-profit groups, and the commercial sector mobilized to stem the tide against an ancient scourge—the result has been an estimated 274 million malaria cases and 1.1 million deaths averted between 2001 and 2010.

And yet, the fight against malaria is far from over and new tools will be needed to continue to build on these initial impressive gains.

Given these gains the World Health Organization (WHO) has undertaken an update of the 2006 Malaria Vaccine Technology Roadmap—a document developed through a consultative process to align the malaria vaccine development community toward common goals. In 2006, the Roadmap set a shorter-term goal—by 2015, develop and license a first-generation malaria vaccine that has a protective efficacy of more than 50% against severe disease and death and lasts longer than one year—which is expected not to change. However, the long-term goal will be updated to better reflect the global health community’s desire to eradicate malaria altogether and targets vaccines that interrupt malaria transmission (VIMTs) and that support the elimination/eradication agenda, including transmission-blocking vaccines (TBV). TBVs are designed to break the cycle of transmission, preventing the malaria parasite from passing from humans to mosquitoes. When used in conjunction with other technologies, a transmission-blocking vaccine could help a country push across the threshold from control to elimination and ultimately help achieve global eradication.

Although there is not an approved malaria vaccine today, several lines of evidence indicate that it is biologically feasible to develop one. A recent update by the WHO of the global malaria vaccine pipeline identified more than two dozen active vaccine candidates in clinical development. This list includes the most clinically advanced candidate, GlaxoSmithKline’s RTS,S, which is in the midst of late-stage Phase 3 trials in Africa. Results to date show that RTS,S cuts cases of malaria in half in toddlers and by one-third in infants, on top of the protection provided by bed nets.

The final set of data from the Phase 3 efficacy trial is expected in 2014, and will provide decision-makers with important information about RTS,S, including vaccine effect in different malaria endemic settings and the impact of a booster dose. And anticipated modeling outputs will illustrate how the vaccine candidate’s efficacy may translate into public health impact—another important input for decisions about the possible role of RTS,S in the future. Experience from vaccines to combat other diseases, such as rotavirus, has shown that the relationship between vaccine efficacy and public health impact is not always straight forward. Rotavirus vaccine efficacy is higher in South Africa than in Malawi (77 percent versus 49 percent – 60 percent greater in South Africa), but the vaccine’s impact in terms of cases averted is actually 60 percent greater in Malawi.

Building on the key learnings from RTS,S, and using unique tools, such as the malaria “human challenge model”, revolutionary new ways to accelerate vaccine development are being used to hunt for additional vaccine targets. The US Government, through multiple cross-sector collaborations, is at the center of much of this research. Initial breakthroughs in malaria vaccine science came from the Department of Defense and the National Institutes of Health—often with the support of USAID. And key elements of the global malaria vaccine pipeline are supported by USAID’s Malaria Vaccine Development Program, which, along with the President’s Malaria Initiative, has been integral to the successes made to date in the fight against malaria. Indeed, it is only through strong partnerships that the overall battle against this disease will be won.

The international community has made phenomenal progress against malaria, but the gains are fragile. More than 650,000 people still die from malaria each year, almost all of them young African children, and history tells us that when support for control programs wanes, the parasite resurges with a vengeance. Over the years, malaria vaccine development has progressed from a pipe dream to a pipeline, and adding a vaccine to the arsenal is more important than ever to vanquish this parasite. At the turn of the next century, malaria should exist only in the annals of eradicated infectious diseases.

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ZIMENE MUMAKONDA

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