Malaria

Malaria in short

• an infectious disease caused by protozoan parasites of the genus Plasmodium
• the parasite is transmitted by Anopheles mosquitoes
• is curable and preventable
• without treatment, infection is often fatal
• an effective vaccine is not available
• kills more than 1 million people each year, half of them children under 5 years of age
• according to estimates, between 250 and 500 million people become ill annually
• Every 30 seconds a child dies of malaria

Malaria in detail

Pathogenic agent
Malaria is caused by parasites of the genus Plasmodium. Four species are pathogenic for humans: Plasmodium falciparum, P. vivax, P. ovale and P. malariae. P. falciparum is the most devastating of the parasite species and is responsible for the majority of malaria deaths.

Transmission/pathogenesis
Malaria parasites undergo a complex life and developmental cycle that takes place in the mosquito as well as in the human host. Humans acquire Plasmodium when they are bitten by an infected female Anopheles mosquito; sporozoites within the saliva of the mosquito enter the bloodstream as soon as an infected female feeds on blood. The sporozoite then embeds itself in a liver cell to form a schizont. The schizont grows for several days (depending on the parasite species between 5 and 18 days) before releasing hundreds to thousands of daughter cells called merozoites. In P. falciparum infections, a single sporozoite produces 30,000 to 40,000 merozoites within 5–7 days.

The merozoites infect red blood cells, where they multiply (a P. falciparum merozoite produces 8–24 copies within 48 hours). The blood cells finally rupture, releasing the merozoites, which then infect more red blood cells. A few merozoites develop into gametocytes, which remain in the blood for a few days and might be ingested by a feeding mosquito.

In the mosquito gut, the gametocytes develop into male and female gametes. These merge sexually and produce an ookinete, which grows into an oocyst. When the oocyst ruptures, sporozoites are released. The sporozoites migrate to the salivary glands, and with the next bite they may be transmitted to the next human, and the cycle starts again...

P. vivax and P. ovale have the ability to produce dormant liver stage parasites in the human host, called hypnozoites. These may rest for months or even years before getting reactivated and causing a typical malarial relapse.

Symptoms
The repeated infection of red blood cells depletes the body of oxygen and usually leads to the onset of the classic malaria symptoms such as fever, chills, sweating, headache or muscle pains. Some patients develop severe complications with sometimes fatal consequences, e.g. cerebral malaria, anaemia or kidney failure. Others, however, do not show symptoms at all. The severity of infection depends on the type of parasite, the genetic background of the host and its immune system. Most devastating is the so-called malaria tropica caused by P. falciparum, with lethality of up to 20%.

Treatment
Several chemotherapeutics are able to successfully treat malaria and prevent complications and death. Quinine and its derivatives as well as antifolate combination drugs are the most widely used chemical agents. Treatment should start as early as possible and depends on the infecting parasite, possible drug resistance and the severity of symptoms.

Resistance to antimalarial drugs is threatening malaria control in many countries. According to the World Health Organization (WHO), two of the four malaria parasites naturally infecting humans have already developed resistance. P. falciparum has acquired resistance against all antimalarials currently used ,"although the geographical distribution of resistance to any single antimalarial drug varies greatly". Chloroquine and/or primaquine have lost efficacy to treat P. vivax infections in some regions.

Prevention
Control of the malaria vector – the Anopheles mosquito – is the main objective of global malaria control. The two basic interventions are Indoor Residual Spraying of long-acting insecticides (IRS) and the use of Long-Lasting Insecticidal Nets (LLIN). These have been shown to effectively stop transmission of the malaria parasites and reduce the number of infections. However, increasing resistance of vector mosquitoes to insecticides is currently hampering efforts to protect populations at risk.

Vaccination
A malaria vaccine is not available. Several candidate drugs are being tested, and one agent reached phase III clinical studies in 2009. This drug (RTS,S/AS01) was promising in phase II studies, providing both infants and young children with significant protection against malaria.

Epidemiology, incidence and mortality
Approximately 40% of the world’s population is at risk of malaria because they live in areas where the disease is transmitted. Most affected is Africa, were about 90% of cases occur, but malaria is found in tropical and subtropical regions around the world (excluding Australia). According to the WHO World Malaria Report 2008, 247 million cases occurred globally in 2006. Over 1 million people die annually, with children under 5 years of age being at most risk.

Due to improved access to malaria control measures, e.g. bed nets or indoor spraying, death rates have dropped significantly in some African countries. Eritrea, Rwanda and São Tomé and Principe, for example, reported reductions in malaria deaths by 50% or more between 2000 and 2006/7.
For more information see the WHO World Malaria Report 2008 (www.who.int/malaria/wmr2008).

Airport malaria
Outside of malaria-endemic regions, sporadic cases might occur due to so-called "airport malaria" or "baggage malaria". In these cases, an infected mosquito "travels" in airplanes or  passenger baggage into malaria-free regions and infects people living around the airport.

To know or not to know...
Four Nobel Prizes have been awarded for work associated with malaria: Sir Ronald Ross (1902), Charles Louis Alphonse Laveran (1907), Julius Wagner-Jauregg (1927) and Paul Herrmann Müller  (1948). A fifth Nobel Prize went to Camillo Golgi in 1906 for his work on the nervous system. Golgi contributed a lot to malaria research, too.

More information
- WHO Global Malaria Programme: www.who.int/malaria/
- WHO World Malaria Report 2008: www.who.int/malaria/wmr2008
- The Global Fund to Fight Aids, Tuberculosis and Malaria: www.theglobalfund.org/en/
- The Initiative for Vaccine Research on Malaria: www.who.int/vaccine_research/diseases/soa_parasitic/en/index4.html
- The European Malaria Vaccine Initiative: www.emvi.org
WHO tropical disease research – Malaria: http://apps.who.int/tdr/svc/diseases/malaria

Literature
- WHO fact sheet on Malaria: www.who.int/mediacentre/factsheets/fs094/en/index.html
- WHO World Malaria Report 2008: www.who.int/malaria/wmr2008
- RobertKoch Institute (in German only): www.rki.de/cln_100/nn_494530/DE/Content/Infekt/EpidBull/Merkblaetter/Ratgeber__Mbl__Malaria.html
Centers for Disease Control and Prevention on Malaria: www.cdc.gov/malaria/
- The Initiative for Vaccine Research on Malaria: www.who.int/vaccine_research/diseases/soa_parasitic/en/index4.html
- Abdulla S, Oberholzer R, Juma O, et al. Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. N Engl J Med 2008. 359: 2533–44. doi:10.1056/NEJMoa0807773
- Bejon P, Lusingu J, Olotu A, et al. Efficacy of RTS,S/AS01E Vaccine against Malaria in Children 5 to 17 Months of Age. N Engl J Med 2008. 359: 2521-32. doi:10.1056/NEJMoa0807381