Optimally timing primaquine treatment to reduce Plasmodium falciparum transmission in low endemicity Thai-Myanmar border populations

• Published in: Malaria Journal
• Main Authors: Hungerford Laura L, Maneeboonyang Wanchai, Thanyavanich Nipon, Yimsamran Surapon, Singhasivanon Pratap, Klein Eili Y, Lawpoolsri Saranath, Maguire James H, Smith David L
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2009
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-8-159; https://doaj.org/article/dd736058011b43e391e52641024610da

Abstract Background Effective malaria control has successfully reduced the malaria burden in many countries, but to eliminate malaria, these countries will need to further improve their control efforts. Here, a malaria control programme was critically evaluated in a very low-endemicity Thai-Myanmar border population, where early detection and prompt treatment have substantially reduced, though not ended, Plasmodium falciparum transmission, in part due to carriage of late-maturing gametocytes that remain post-treatment. To counter this effect, the WHO recommends the use of a single oral dose of primaquine along with an effective blood schizonticide. However, while the effectiveness of primaquine as a gametocidal agent is widely documented, the mismatch between primaquine's short half-life, the long-delay for gametocyte maturation and the proper timing of primaquine administration have not been studied. Methods Mathematical models were constructed to simulate 8-year surveillance data, between 1999 and 2006, of seven villages along the Thai-Myanmar border. A simple model was developed to consider primaquine pharmacokinetics and pharmacodynamics, gametocyte carriage, and infectivity. Results In these populations, transmission intensity is very low, so the P. falciparum parasite rate is strongly linked to imported malaria and to the fraction of cases not treated. Given a 3.6-day half-life of gametocyte, the estimated duration of infectiousness would be reduced by 10 days for every 10-fold reduction in initial gametocyte densities. Infectiousness from mature gametocytes would last two to four weeks and sustain some transmission, depending on the initial parasite densities, but the residual mature gametocytes could be eliminated by primaquine. Because of the short half-life of primaquine (approximately eight hours), it was immediately obvious that with early administration (within three days after an acute attack), primaquine would not be present when mature gametocytes emerged eight days after the appearance of ...