Malaria & Vaccines
A life-threatening infectious disease
Malaria is the most widespread and deadly parasitic disease in the world with over half of the world's population living where the disease is prevalent. 
A serious and sometimes fatal disease, malaria exerts enormous pressure on healthcare systems in Africa and beyond, as the illness can rapidly deteriorate to severe malaria and progress into life-threatening complications causing death. It also imposes substantial costs to both individuals and governments. Direct costs have been estimated to be at least 12 billion dollars per year. 
Despite the remarkable progress achieved by malaria control efforts over the last decade, malaria is endemic and is still a leading cause of mortality and morbidity worldwide. The World Health Organization (WHO), which monitors the disease, warns that malaria still kills 800-1000 children under the age of 5 daily. Globally, more than 200 million cases were estimated to have occurred in 2016. Young children and pregnant women in Africa are at highest risk but so are travellers, workers and migrants in endemic areas.
Most experts agree that the substantial success in malaria control is fragile and could be easily undermined by lack of funds. Of great concern is the fact that malaria control tools are constantly threatened by growing resistance to insecticide and drugs, changes in malaria transmission, environmental conditions all further complicating the potential solutions to attain the goal of elimination.
All this underlines the critical need for safe and highly effective malaria vaccines that would add an important, complementary tool to the existing interventions and avert significant illness and deaths. 
Causes and Transmission
The Plasmodium parasite is transmitted to humans by the bites of malaria infected female Anopheles mosquitoes. Of the five species known to infect humans, the deadliest is Plasmodium falciparum, which is responsible for almost all the disease mortality and is the dominant strain in sub-Saharan Africa. Beyond Africa, Plasmodium vivax malaria is more prevalent.
The parasite develops in the red cells and therefore in rare instances can be transmitted via blood transfusion, organ transplant and use of medical equipment such as needles, scalpels and syringes contaminated with malaria infected blood. 
Pregnant women infected with malaria can also transmit the parasite to their unborn child before or during delivery. 
Malaria transmission and its intensity are influenced by various factors related to the complex life-cycle of the parasite, that effect the mosquito vector, the human host and the environment and climate.
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Source: Klein EY. Antimalarial drug resistance : a review of the biology and strategies to delay emergence and spread. Int. J Antimicrob agents (2013). 
Populations at Risk
The World Health Organization (WHO) estimates that up to half of the world's population is at risk of malaria. In 2016, transmission was reported in more than 91 countries, across South-East Asia, Latin America, the Middle-East, and Sub-Saharan Africa, where the majority of cases and death occur (80%).
Populations who are highly exposed to bites of Plasmodium falciparum infected Anopheles mosquitoes are at risk of dying from malaria. At highest risk are young children, pregnant women, non-immune patients as well as travelers and migrants who are the most susceptible to malaria infection.
Malaria is an acute febrile illness which can present as a flu-like illness. The symptoms of malaria (in non-immune individuals) typically develop within 10-15 days following the infection. These include : fever, chills, sweats, headaches, nausea, vomitting, body aches and malaise. The disease causes destruction of red blood cells and may lead to anemia and jaundice. 
Without prompt treatment, malaria can rapidly deteriorate and become a life-threatening disease. Severe complications, such as respiratory distress, kidney failure, severe anemia, seizures, coma can follow resulting in death. 
Tens of millions of individuals travel each year to malaria areas and seek malaria prophylaxis from their doctors.
Prevention & Control Measures
Prevention of malaria is currently based on two complementary methods: 
  • Chemoprophylaxis (providing drugs to suppress the infection) and
  • Protecting against mosquito bites by controlling the vector (mosquito).
  • Chemoprevention is mainly for travelers to malaria endemic countries. The drug choice is related to various factors such as the destination, the duration of stay, the individual's age, etc. 
  • Antimalarial drugs are now also recommended under certain conditions for pregnant women, infants and young children (under the age of 5) living in moderate and high transmission areas.
Vector Control
Reducing the contact between the vector (mosquitoes) and humans is the main way to prevent and reduce malaria transmission. 
There are 2 forms of vector control that can be widely effective: 
  • Insecticide-treated mosquito nets
Malaria transmission occurs primary at night. Therefore, the main and most powerful way to protect humans against mosquito bites is the use of Insecticide-Treated mosquito Nets (ITNs), preferably Long-Lasting Insecticidal Nets (LLINs).
  • Indoor spraying with residual insecticides
Another prevention method is the Indoor Residual Spraying (IRS) with insecticides. Its effectiveness lasts for 3–6 months.​
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Diagnosis & Treatment
Rapid diagnosis and treatment of malaria is imperative to prevent complications, deaths and transmission.
All persons suspected to have malaria should be treated for the presence of malaria parasites in their blood through slide microscopy examination or rapid diagnostic test (RDT). 
If a diagnosis is not possible, WHO recommends considering treatment based only on symptoms. 
Treatment of uncomplicated Plasmodium falciparum malaria is now highly dependent on Artemisinin Combination Therapy (ACT). ACTs combine drugs with different mechanisms of action and are the most effective therapy available today. The choice of ACT should be based on the results of therapeutic efficacy studies against local strains of Plasmodium falciparum malaria.
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Drawbacks with current malaria prevention, control and treatment measures
Massive international aid 2000-2015 has led to a decrease in global malaria incidence and deaths. But this is happening at the expense of inducing resistance to insecticides and anti-malarial drugs: since 2016, the gains have stalled.
  • Insecticide Resistance 
After the extensive ITN use over the last few years, the insecticide efficacy is reduced and the risk of rebound is increasing. According to WHO, resistance to one or more insecticides was reported in all regions in 2016.
Therefore, while ITN continues to be an effective prevention tool, the threat of resistance continues to grow.
  • Antimalarial Drug Resistance
Artemisinin, the cornerstone of malaria treatment and control, is already facing resistance, not surprising given the fact that resistance has evolved to almost every anti-malarial drug in use.
    • Widespread use of artemisinin-based drug combinations puts increasing pressure on malaria parasite
    • Alternatives are limited and the drug development pipeline is not promising
Artemisinin resistance is spreading in South East Asia. Fortunately, this resistance is still contained in 5 countries of the Greater Mekong subregion: Cambodia, Lao People’s Democratic Republic, Myanmar, Thailand and Viet Nam. However, some places are close to 100% resistance to artemisinin.
Vaccines against Malaria
Considering the current situation and the existing challenges, safe malaria vaccines that are highly protective could avert significant illness and deaths. 
Vaccines have by far the best cost-effectiveness ratio and international financial mechanisms now exist to support their purchase and distribution (Global Alliance for Vaccines and Immunization-GAVI, Global Fund).
According to GAVI, a malaria vaccine with 50% efficacy could avert 450,000 deaths annually.
However, limitations of the first-generation malaria vaccine, such as RTS,S, underscore the need for “second generation vaccines with higher efficacy to further reduce malaria cases and deaths".  
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Source: Vaccine Investment Strategy Project GAVI Alliance Presentation to CSO Steering Committee, 8 June 2017