Malaria

In 2015, according to WHO estimations (World Malaria Report 2016), there were 429.000 deaths from malaria globally, the vast majority of which -99%- caused by P. falciparum. Most deaths are estimated to have occurred in the African region. Seventy percent of all malaria deaths have occurred in children under 5 years of age, meaning that despite a decrease in infant mortality due to malaria since 2010, malaria remains a major killer of children. Overall, malaria mortality rates are estimated to have decline by 62% globally between 2000 and 2015 and by 29% between 2010 and 2015. Despite improvements in malaria mortality over the last 20 years, these figures highlight the continuing need for malaria vaccines as one of the major tools to prevent and ultimately eliminate malaria.

WHO - World Malaria Report 2016
Malaria Vaccine Technology Roadmap
WHO Preferred Product Characteristics for Malaria Vaccines (WHO/IVB/14.09)
WHO: Tables of malaria vaccine projects globally

Cause

Malaria is caused by four species of the single-celled parasite plasmodium. This has a complex life cycle in humans, passing initially through the liver but causing all its clinical effects when it enters the bloodstream and destroys red blood cells.

Transmission of Plasmodium is by a vector female Anopheles mosquito feeding on the blood from an uninfected human after having previously fed on the blood of a human infected with malaria parasites.

Consequences

The impact of malaria in sub-Saharan Africa, the worst affected continent, is mainly on children and pregnant women, particularly in poor rural areas.  Young children suffer fever, headache, anaemia and vomiting.

In its rarer severe form, malaria can cause coma, respiratory distress, metabolic disorders and severe anaemia.  Up to 30% of children with severe malaria will die.  For those who survive, impaired learning or neurological deficits are common although natural immunity is also gradually built up.

Pregnant women and their unborn children suffer from maternal anaemia, low birth weight, prematurity and neonatal deaths.

Under less intense transmission (as in much of Asia and South America), P. falciparummalaria affects adults as well as children, causing fever and the potentially fatal severe form.  The burden of P. vivax malaria, particularly in Asia, is also becoming increasingly apparent.

Global burden

Malaria impacts individuals, communities and the economy.  There are an estimated 350-500 million malaria episodes every year, in more than 100 countries covering more than 40% of the world population (Robert W. Snow, Carlos A. Guerra, Abdisalan M. Noor, Hla Y. Myint & Simon I. Hay. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434, 214-217 10 March 2005).

Most malaria is caused by P. falciparum.  Around 90% of cases worldwide are in children aged under five in Africa.  Africa  has a virulent form of the P. falciparum parasite, efficient mosquito vector and a climate conducive to the spread of malaria.  African children also suffer 80% of the 1 million deaths each year, an equivalent of one child every 30 seconds.

Malaria is estimated to cost sub-Saharan Africa US$ 12 billion in Gross Domestic Product every year and to restrict economic growth by 1.3% per year (ref?).  Malaria is thus both a cause and a consequence of poverty (Jeffrey Sachs & Pia Malaney.  The economic and social burden of malaria. Nature 415, 680-685 7 February 2002).

Vaccines

Current malaria control methods, notably new Artemisinin Combination Drug Therapies (ACTs), insecticide-treated nets and residual spraying, have led to reduced disease burdens in some countries. However, P. falciparum is already showing signs of resistance to ACTs and the mosquito has historically always developed resistance to insecticides. A partially effective vaccine could reduce the global disease burden, but only a highly effective vaccine would offer the prospect of malaria elimination.

Approaches to malaria vaccine development target various stages in the parasite life cycle:

  • Pre-erythrocytic vaccines - these target the early stage when the parasite is entering the liver
  • Asexual blood-stage vaccines - these aim to reduce infection of red blood cells and consequently, prevents clinical disease
  • Transmission-blocking vaccines - these prevent the parasite from maturing in the mosquito. They would need to be combined with another type of vaccine to protect the vaccinated individual.

Recent advances in the understanding of malaria in pregnancy also give hope that a vaccine targeted specifically against malaria infection of the placenta is feasible.