Malaria

Malaria is by far the world’s most important tropical parasitic disease. An estimated 300 – 500 million people become ill each year. Malaria is due to infection with the Plasmodium parasite, a small single cell organism. In principle 4 Plasmodium species can cause disease in humans, but infections with P. falciparum are the most important. The disease kills an estimated two - three million people per year, mainly young children in developing countries. Approximately 1 child dies every 30 seconds due to malaria. Other important risk groups are pregnant women and non-immune travellers.

Transmission of the parasites from man to man occurs via the bite of infected blood-feeding female mosquitoes (Anopheles). Inside the human body, the malaria parasites multiply extremely rapidly in the liver. At a certain time point, they leave this organ and subsequently infect red blood cells (erythrocytes). A next wave of Plasmodium replication takes place in the erythrocytes, then the red blood cell bursts, followed by infection of new red blood cells by the parasites. Malaria begins as a flu-like illness 8 - 30 days after infection. Symptoms include fever, with or without other symptoms like headache, pain in the muscles, vomiting, diarrhoea and cough. Typical cycles of fever with shaking chills and drenching sweats may develop. Destruction of the erythrocytes leads to severe anaemia. Death may be due to infected red blood cells blocking blood vessels in the brain (cerebral malaria) or damage to other vital organs (e.g. liver and kidneys).

Prompt, accurate diagnosis and effective treatment are corner stones of effective malaria management. Clinical diagnosis is not always very easy, as primary symptoms may resemble those of other diseases (flu). Therefore, laboratory diagnosis is very important and this has up to now relied almost exclusively on microscopy.

Malaria is in principle a curable disease. However, the parasite is capable of becoming resistant to the action of anti-malaria drugs. This is due to small changes in the parasite DNA. Over-prescription of anti-malarials (confusion with other febrile diseases) and uncontrolled selling of poor quality drugs contribute to the increase in drug resistant parasites. There is a big need to develop and test new anti-malaria drug(s) or drug combinations.

 

 

 

Approach

KIT Biomedical Research conducts, in collaboration with partner institutes in Africa, Vietnam and the Netherlands, research towards improved diagnosis and treatment. We have gained ample experience in the development and improvement of diagnostic procedures of malaria and the development of molecular techniques for the detection and quantification of very low numbers of parasites in blood samples. Furthermore, we perform research on drug efficacy and drug resistance and have all the required technologies in-house to conduct these types of studies.

Focal points

  • Development, evaluation and implementation of diagnostic tools for malaria
  • Improvement of diagnosis of malaria in rural laboratories
  • Treatment of malaria, participation in clinical trials
  • Drug resistance marker studies (molecular biology)
  • Strain differentiation via molecular techniques
  • Transfer of developed technologies to disease endemic countries
  • Advice to researchers, policy makers and health workers

Example

Plasmodium falciparum malaria parasites can be transmitted from man to mosquito when mosquitoes ingest the sexual parasite stages (gametocytes) during blood feeding. These gametocytes occur in relatively small numbers when detected by microscopy, but malaria is transmitted efficiently.

KIT Biomedical Research and Nijmegen University have developed a molecular technique (QT-NASBA) for quantification of various stages of P. falciparum parasites, based on real-time RNA amplification, which is considered more sensitive than microscopy and more practical in use than other methods.

QT-NASBA was used to study parasite dynamics in volunteers with experimental P. falciparum infections. It was demonstrated that sexual development starts immediately during blood stage infection, although without subsequent maturation into full-grown gametocytes.

The efficacy of drug treatment and its effect on gametocytes was studied in Kenyan children with P. falciparum malaria. Three different drug regimens, all had a higher clinical efficacy than sulphadoxine-pyrimethamine (SP), which is the most widely used drug in Kenya for the treatment of malaria. Additionally, a reduction of gametocytes was observed after artemisinin combination therapy (a new drug combination). Although artesunate combination therapy resulted in significantly lower prevalence and density of gametocytes compared to SP monotherapy, it did not eliminate all gametocytes. Many children harboured gametocytes both before and after treatment with SP or SP + artesunate, often at densities below the microscopical detection limit. The frequent presence of submicroscopic gametocytaemia was confirmed in individuals of all ages in Burkina Faso.

To investigate the epidemiological importance of submicroscopic gametocytes, various concentrations of gametocytes were fed to mosquitoes both in the laboratory and in the field and subsequent mosquito infections were monitored. Even though the probability of mosquito infection increases with the gametocyte density, submicroscopical gametocyte densities can still infect mosquitoes. With the large number of Kenyan children with submicroscopic gametocytaemia, this group may be responsible for approximately half of the transmission.

 

 

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Team members


Contact

For more information, please contact Dr. Henk Schallig or Dr. Pètra Mens

Tags

malaria | disease control | diagnostics | infectious diseases | research |

Royal Tropical Institute