Since the start of the Bangkok Unit in 1979, malaria has been one of our main research topics. In the 1980s and 1990s falciparum malaria was still a major health problem in Thailand, so studies focused on the pathophysiology and treatment of severe malaria and the treatment of multi-drug resistant uncomplicated falciparum malaria.
In those years the very potent and efficacious antimalarial drugs called artemisinins became available outside China for the first time. Early studies conducted by the Malaria Department were pivotal in the conception and testing of artemisinin combination therapies (ACT), now the mainstay for the treatment of uncomplicated falciparum malaria throughout the malaria endemic world.
Highly efficacious, ACTs affect both the asexual blood stages and the gametocytes responsible for transmission, and have contributed importantly to the large decline in falciparum malaria transmission in Thailand and other countries.
With falciparum malaria declining, the Malaria Unit has increasingly studied the biology and treatment of the tertian malaria Plasmodium vivax, which has become relatively more important. Although rarely causing death, P. vivax is an important source of febrile illness. Like falciparum malaria it causes abortion and low birth weight when infection occurs during pregnancy. Unlike falciparum malaria, P. vivax has dormant forms in the liver called hypnozoites that can cause relapse of the disease for many years after the initial infection. The understanding of the dynamics and periodicity of these relapse infections has been importantly advanced through the work of the Malaria Department.
Another key Malaria Department research achievement resulted from our studies on optimising antimalarial drug treatment for severe falciparum malaria.
The two largest-ever treatment trials in severe malaria, which compared parenteral artesunate with quinine, were conducted by our unit: SEAQUAMAT (2005) in Asia in 1,461 patients and AQUAMAT (2010) in Africa in 5,425 children. These trials provided definite proof that artesunate should replace quinine as first line treatment for severe malaria in all endemic settings. This recommendation was endorsed by the World Health Organization (WHO) and included in its malaria treatment guidelines.
Research on severe malaria pathophysiology has focused on quantifying the importance of the compromised microcirculation in severe malaria. The Department developed a method to visualize blocked microcirculation in patients using a microscopic camera and retinal photography, and also developed a method to estimate the hidden sequestered parasite burden through measurement of plasma PfHRP2, a parasite protein released at the moment of schizont rupture.
In recent years cracks have appeared in the efficacy of the ACTs. A landmark paper from our Unit showed unambiguously for the first time resistance of P. falciparum to artemisinins in western Cambodia, characterized by remarkable slower parasite clearance. This parasite phenotype was shown to be a prelude to failure of several ACTs in cases with concomitant reduced sensitivity towards the partner drug of the ACT.
In addition to P. falciparum and P. vivax, the Malaria Department’s research programme has also studied human malaria caused by P. ovale, P. malariae, and P. knowlesi, which jump species from macaque monkeys to humans. The molecular lab has studied extensively the molecular determinants of antimalarial drug resistance in all the human malaria species, such as the mutations in the dhfr-ts genes of Plasmodium conferring anti-folate resistance. Dr. Naowarat Tanomsing’s work on this gene in P. ovale helped to identify two non-recombining sympatic forms within the till then single species P. ovale.
A similar conclusion based on different genes was drawn by Dr. Colin Sutherland and the reports were combined to announce the two novel separate species. The team is now exploring the population biology and epidemiology of these two newly recognized human malaria parasite species.