2. Current malaria burden and need for elimination/eradication

Malaria is the most important parasitic disease and is endemic across the globe, most importantly sub-Saharan Africa, South and Southeast Asia, Papua New Guinea, and South America. Its burden remains unacceptably high, especially in sub-Saharan Africa, despite the significant gains with the use of current tools including vector control, diagnostics, chemoprevention and treatment. In 2016, 216 million malaria cases and 445,000 deaths were recorded worldwide mostly caused by Plasmodium falciparum, 90% of which occurred in sub-Saharan Africa [1]. Since artemisinins constitute the core component of the current malaria treatments, the recent emergence of artemisinin resistance in Southeast Asia [2–4] has become a serious obstacle for the malaria elimination agenda. Although the current phenotypes of artemisinin resistance are limited to slow parasite clearance and parasite recrudescence, their impact in malaria-endemic areas could result in a considerable increase of malaria cases, deaths, and economic costs according to predictive models [5, 6]. Indeed, the probable spread of artemisinin resistance to sub-Saharan Africa, where the burden of malaria is the highest, could jeopardize the lives of millions of children. Furthermore, the spread of insecticide and mosquito behavioral resistance compromises malaria control via the failure of vector control interventions such as indoor residual spraying (IRS) and insecticide-treated nets (ITN). Given that current strategies will eventually fail, new tools are urgently needed for malaria control and treatment. To overcome these constraints, transmission-blocking vaccines (TBVs) offer a new approach by targeting developing parasites in the mosquito host (a bottleneck in the malaria parasite lifecycle) and thereby contributing to malaria elimination and potentially eradication.

#### 3. Need for malaria vaccine strategy

Vaccines are powerful tools that could accelerate malaria elimination efforts. Historically, vaccine-based strategies have contributed to the successful eradication of infectious diseases in humans and animals, including smallpox and rinderpest [7, 8]. Poliomyelitis is now close to eradication through routine Expanded Programme on Immunization (EPI) and massive immunization campaigns in some areas. Vaccination is a safe and cost-effective strategy that is easily implemented in large populations to reduce or even eliminate disease morbidity and mortality. Vaccine-induced immune responses protect individuals against infection or disease and can also stop transmission of the causative agent. With high coverage, vaccines protect not only recipients but also non-immunized individuals within the population through the effect of herd immunity. Malaria vaccines, even those with modest efficacy, such as the RTS,S product (see below in "Current status of malaria vaccine research"), are expected to avert millions of clinical malaria cases and thousands of severe malaria cases, hospitalizations, and deaths, according to prevalence-based predictive models [9–11]. The complex malaria parasite lifecycle (Figure 1) offers several stages that can be targeted by various vaccine strategies,

Figure 1. Malaria parasite life cycle and vaccine targets. Transmission-blocking vaccines are directed against the sexual stages of malaria parasite development in the mosquito, while other stages of the parasite life cycle can be targeted with different vaccine approaches. The vaccine concepts, candidate vaccines, and candidate antigens discussed in this chapter are presented according to their targeted stage of the parasite life cycle, as well as their anticipated biological effects: transmission-blocking, anti-infection, and anti-disease effects. Illustration by Alan

Malaria Transmission-Blocking Vaccines: Present Status and Future Perspectives

http://dx.doi.org/10.5772/intechopen.77241

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Current malaria vaccine approaches target various parasite lifecycle stages including liver and blood stages in the individual and sexual stages in the mosquito (Figure 1). Liver stage vaccines, best typified by whole sporozoite (SPZ) vaccines that induce sterile protection [12], presumably act through T cell responses [13] and possibly antibodies and prevent progression of liver stage infections to blood stage parasitemia. Blood stage vaccines on the other hand

which in combination may interrupt transmission.

Hoofring, Medical Arts Design Section, NIH.

4. Benefits of malaria transmission-blocking vaccines

(TBV), which will contribute to malaria elimination and eradication. We place TBV in the context of overall malaria vaccine development and highlight the role and challenges of TBV

Malaria is the most important parasitic disease and is endemic across the globe, most importantly sub-Saharan Africa, South and Southeast Asia, Papua New Guinea, and South America. Its burden remains unacceptably high, especially in sub-Saharan Africa, despite the significant gains with the use of current tools including vector control, diagnostics, chemoprevention and treatment. In 2016, 216 million malaria cases and 445,000 deaths were recorded worldwide mostly caused by Plasmodium falciparum, 90% of which occurred in sub-Saharan Africa [1]. Since artemisinins constitute the core component of the current malaria treatments, the recent emergence of artemisinin resistance in Southeast Asia [2–4] has become a serious obstacle for the malaria elimination agenda. Although the current phenotypes of artemisinin resistance are limited to slow parasite clearance and parasite recrudescence, their impact in malaria-endemic areas could result in a considerable increase of malaria cases, deaths, and economic costs according to predictive models [5, 6]. Indeed, the probable spread of artemisinin resistance to sub-Saharan Africa, where the burden of malaria is the highest, could jeopardize the lives of millions of children. Furthermore, the spread of insecticide and mosquito behavioral resistance compromises malaria control via the failure of vector control interventions such as indoor residual spraying (IRS) and insecticide-treated nets (ITN). Given that current strategies will eventually fail, new tools are urgently needed for malaria control and treatment. To overcome these constraints, transmission-blocking vaccines (TBVs) offer a new approach by targeting developing parasites in the mosquito host (a bottleneck in the malaria parasite lifecycle) and

field trials, which are needed to confirm activity and guide implementation.

364 Towards Malaria Elimination - A Leap Forward

thereby contributing to malaria elimination and potentially eradication.

Vaccines are powerful tools that could accelerate malaria elimination efforts. Historically, vaccine-based strategies have contributed to the successful eradication of infectious diseases in humans and animals, including smallpox and rinderpest [7, 8]. Poliomyelitis is now close to eradication through routine Expanded Programme on Immunization (EPI) and massive immunization campaigns in some areas. Vaccination is a safe and cost-effective strategy that is easily implemented in large populations to reduce or even eliminate disease morbidity and mortality. Vaccine-induced immune responses protect individuals against infection or disease and can also stop transmission of the causative agent. With high coverage, vaccines protect not only recipients but also non-immunized individuals within the population through the effect of herd immunity. Malaria vaccines, even those with modest efficacy, such as the RTS,S product (see below in "Current status of malaria vaccine research"), are expected to avert millions of clinical malaria cases and thousands of severe malaria cases, hospitalizations, and

3. Need for malaria vaccine strategy

2. Current malaria burden and need for elimination/eradication

Figure 1. Malaria parasite life cycle and vaccine targets. Transmission-blocking vaccines are directed against the sexual stages of malaria parasite development in the mosquito, while other stages of the parasite life cycle can be targeted with different vaccine approaches. The vaccine concepts, candidate vaccines, and candidate antigens discussed in this chapter are presented according to their targeted stage of the parasite life cycle, as well as their anticipated biological effects: transmission-blocking, anti-infection, and anti-disease effects. Illustration by Alan Hoofring, Medical Arts Design Section, NIH.

deaths, according to prevalence-based predictive models [9–11]. The complex malaria parasite lifecycle (Figure 1) offers several stages that can be targeted by various vaccine strategies, which in combination may interrupt transmission.
