Question 10 Discuss drug treatments against malaria

#10 - Discuss drug treatments against malaria.

By Russell Allen

Malaria is the leading cause of death in developing countries. WHO estimates around 300-500 million people are infected with malaria each year, resulting in nearly 3 million deaths annually. Around 90% of these deaths occur in sub-Saharan Africa. Around 2.24 billion people, over 40% of the worlds population, are at a daily risk of contracting the potentially fatal disease. These statistics are staggering, considering the prophylactic and effective treatments available from the local pharmacy.

There are four different Plasmodium species of capable of causing malaria: P. ovale, P. malariae, P. vivax, and the most common P. falciparum, to which its current prevalence owes its success. P. falciparum exploits the capacity of antigenic variation to evade the attempts so far tried to eradicate the disease. In 1955 the World Health Organisation launched the Global Malaria Eradication Program, emphasizing vector control through the use of DDT spraying and national surveillance. Due to the enormous malarial reservoir present in sub-Saharan Africa, and the poor economic status of the countries which harboured the disease, it was determined that this region could not support the infrastructure required for an effective eradication program, and was largely ignored throughout the campaign. Countries involved in the campaign, including most of Europe and the United States, saw great success with a rapid decline in malaria cases. However in 1965 the project had begun to fall apart in countries like India, where political unrest and population movements contributed to the rise of the deadly disease. In 1969 the campaign was declared a failure, doomed by the inflexibility of the control measures required to sustain its success. But the biggest failure was yet to be seen. Drug resistance developed by P. falciparum meant a new form of the plasmodium had emerged, deadlier than ever. Resistance to chloroquine compounded the already devastating pathogenicity of the disease, and its effects continue to be apparent in todays endemic regions.

Many synthetic quinine analogues have since been produced to treat malaria. Chloroquine is still a highly effective initial therapy for all four human malarias, except of course the chlorquine-resistant strains of P. falciparum. Quinine, the original botanic treatment for malaria isolated from chincona bark in the 17th century, given intravenously remains an effective choice for severe malaria infections.

Regimens are often implemented to completely eradicate the parasite from the blood, and from exo-erythrocytic stages of the plasmodium life cycle, primarily in the liver. For such regimens, pyrimethamine/sulfadoxine combinations are used. Pyrimethamine inhibits the enzyme dihydrofolate reductase (DHFR), blocking the production of nucleic acids, with a much higher affinity to protozoal organisms than that of the mammalian host. Sulfadoxine works synergistically to block the same substrates, and sequentially inhibit the protozoans ability to utilize folate, essential for nucleic acid synthesis.

Doxycycline is indicated for the prevention of recurring malaria due to dormant hypnozoites in the liver. Again, this treatment follows initial therapy with quinine to eliminate both blood and tissue etiologies.

There are a range of prophylactic treatments, determined by the area destined for travel. These areas are categorized by their resistance or sensitivity to malarial drugs chloroquine and mefloquine. Other factors include length of stay, activities planned, availability of healthcare, and age. The prophylactic regimens often initiate treatment in the week leading up to the travel date, as well as one tablet daily whilst in affected areas, and completed with a daily dose up to 4 weeks after leaving such areas.

People travelling to areas where malaria is endemic are highly susceptible to being infected with malaria, even with prophylactic treatment. The goal of the treatment is not to prevent malaria infection, but rather prevent its progression into the debilitating stages of its complex life cycle. Initiatives such as the Roll-back Malaria Partnership and The Global Fund aim to provide leadership, guidance and funding to an effective eradication campaign. Much promise is resting on a new clinical trial beginning later this year in Africa, hosted by the Malaria Vaccine Initiative PATH, and funded by the Bill and Melinda Gates Foundation, it will be the biggest trial conducted on children in Africa, and will determine the safety and efficacy of the latest advances in malarial vaccines.