It is argued that growing up in malaria endemic countries restricts early childhood development  preventing children from thriving and reaching their full social and economic potential in life.
Malaria is not just a leading killer of children – it is also an important cause of morbidity. When malaria parasites infect of the central nervous system (CNS), symptoms such as seizures and coma can follow and children may be left with brain injury that is not immediately apparent but can cause a lifetime of disability. Brain infections can cause muscular paralysis, impairment in motor, visual or auditory function, memory, thinking, reasoning, speech and can provoke epilepsy.  Cerebral malaria affects 575,000  children annually. Reliable data on risk and prevalence of later disabilities are scarce, and large scale evidence showing how malaria restricts human development potential is not available. Providing this evidence for policy change is the focus of the program.
Young children enrolled in a previous trial, who survived severe malaria, are being traced and assessed to determine whether and how the episode affected their brain. Reliable evidence on the nature and extent of compromised child development potential is being collected. This should spur efforts to prevent malaria and to increase access to anti-malarial drugs (including rectal artesunate) not just to avoid death, but to avoid future losses in child developmental potential.
- ~12,000 episodes with symptoms of severe malaria were treated with a single dose of rectal artesunate or a placebo in the first intervention.
- Now, at least 7,500 children will be followed up from the previous study.
- ~3,000 children, some of whom had CNS malaria, are being assessed to determine the degree of disability associated with CNS infection on brain function and whether treatment modifies the effect.
This child who is sick became ill when she was 3 years old. She had high fever and convulsions. She is now 11 years old. The fits she had then are still present today. She cannot talk, she cannot walk properly. She is doubly incontinent. She cannot ask for food. She moans a lot. She is completely dependent.
-- Rehema, mother of a young girl who had cerebral malaria
The goal of the innovation is about early treatment of malaria so that lives are saved, and disability is prevented. It has been argued that the future economic development of malaria endemic countries could depend upon the elimination of malaria, because malaria restricts human development potential. Large scale evidence showing limitation of human development potential as a consequence of malaria is not available. Gathering evidence for policy change is our focus.
Everyone needs to understand what the consequences of delayed treatment are, in order to avoid harm. The way we are achieving this is to gather evidence that establishes the link between delayed treatment, CNS symptoms and short and long term disability so clearly that policy makers can act on the basis of the evidence.
Reliable evidence that early treatment of malaria – earlier than happens today – prevents death and disability is our focus. The ideal is for malaria to be avoided, or managed with oral medicines as soon as diagnosed. But if patients in the community have suspected severe malaria, can no longer be treated orally, and need immediate help, they should have emergency treatment with rectal artesunate and rapidly referred to the nearest hospital. Why? Because this prevents death, and lasting brain injury in the survivors.
For severe malaria, artesunate is now the best treatment. Given injectably, it saves more lives than quinine. [1, 2] Given rectally, before referral to hospital, a single dose reduces the risk of death or permanent disability in young children. 
- Grand Challenges Canada
Past Study Funders
- Tropical Disease Research Programme of the World Health Organization (Switzerland)
- UNITAID, Medicines for Malaria Venture (Switzerland)
- Orofino Pharma, (Italy)
- Catalent Pharma Solutions (Germany)
- Scanpharm (Denmark)
- Ministries of Health in Burkina Faso, Nigeria, Uganda, Malawi, Tanzania.
Reliable Follow-up, Ensuring Highest Standard of Implementation
The study is about reliable follow-up of all surviving children from a previous study on severe malaria. The purpose is to determine whether CNS malaria results in long term disability. The study is being implemented to the highest standards, and the highest quality of data is being obtained.
Tracing and Re-Enrolling Children
Tracing and re-enrolling children from the earlier clinical trial was the main logistic challenge. Parents and patients had to travel a long distance to be assessed.
Reliable evidence that early treatment of malaria prevents death and disability is the focus of the team working on this issue. The World Health Organization has already included the recommendation for early treatment with artesunate in its treatment guidelines. However, in order for individual countries to adopt global recommendations, they often need local data on the scale of the problem, and evidence on costs and feasibility of the intervention so that they know the policy implications.
A large study using the medication in Tanzania, Uganda, Ghana and Guineé Bissau has been completed. It is being submitted for publication. Further studies are about to be initiated in Nigeria, Uganda, Burkina Faso and Democratic Republic of Congo.
All patients involved in the original trial were traced. Among the survivors, basic information was obtained on their vital, clinical and socioeconomic status. In addition, all patients who had CNS symptoms in the original trial plus a comparative sample of those who did not were assessed to determine whether CNS malaria increased risk for clinical consequences. Special attention was given to muscular paralysis, motor, visual, hearing, memory, reasoning, speech and epilepsy. More subtle consequences of malaria were also assessed including behavioural changes, cognitive development and educational, social and performance skills. Evaluation in the context of this study included all the parameters above.
Impact of Innovation
- The World Health Organization Malaria Treatment Guidelines now recommends emergency treatment with rectal artesunate as early as possible – i.e. as soon as malaria is suspected – if the patient is unlikely to be able to reach a hospital within 6 hours.
- The previous study found that if patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduced the risk of death or permanent neurological damage. 
Cost of Implementation
Data from 2010 has shown that at low uptake and referral compliance (25%) of treatment, the intervention was estimated to avert 19 disability-adjusted life-years (DALYs; 95% CI 16–21) and to cost $1173 (95% CI 1050–1297) per DALY averted. Under the full uptake and compliance scenario (100%), the intervention could avert 967 DALYs (884–1050) at a cost of $77 (73–81) per DALY averted. 
The current study will provide more reliable estimates of DALYs.
- McCormick, M.C. et al. (1992). “The Health and Development Status of Very Low-Birth-Weight Children at School Age,” Journal of the American Medical Association, 267:16.
- Idro R. et al. (2010) Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatric Research, 2010 Oct;68(4):267-74.
- Murphy, S. C. et al. (2001) Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy. The American Journal of Tropical Medicine and Hygiene, 2001 Jan-Feb;64(1-2 Suppl):57-67.
- Dondorp, A. et al. Artesunate Versus Quinine for Treatment of Severe Falciparum Malaria: a Randomised Trial. Lancet 2005, 366, 717-725.
- Dondorp, A. et al. Artesunate Versus Quinine in the Treatment of Severe Falciparum Malaria in African Children (AQUAMAT): an Open-Label, Randomised Trial. The Lancet 2010, 376, 1647-1657.
- Gomes et al (2009). Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial. Lancet, 373: 557-566.
- Tozan, Y. et al. (2010) Prereferral Rectal Artesunate for Treatment of Severe Childhood Malaria: a Cost-Effective Analysis. Lancet 2010, 376, 1910-1915.
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