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

被引:43
作者
Lawpoolsri, Saranath [1 ,2 ]
Klein, Eili Y. [3 ]
Singhasivanon, Pratap [2 ]
Yimsamran, Surapon [2 ]
Thanyavanich, Nipon [2 ]
Maneeboonyang, Wanchai [2 ]
Hungerford, Laura L. [1 ]
Maguire, James H. [1 ]
Smith, David L. [4 ,5 ]
机构
[1] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA
[2] Mahidol Univ, Fac Trop Med, Dept Trop Hyg, Bangkok, Thailand
[3] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA
[4] Univ Florida, Dept Biol, Gainesville, FL USA
[5] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA
基金
比尔及梅琳达.盖茨基金会;
关键词
MEFLOQUINE-ARTESUNATE; GLOBAL DISTRIBUTION; MINIMUS COMPLEX; EARLY-DIAGNOSIS; MALARIA; GAMETOCYTES; DYNAMICS; AREA; GAMETOCYTOGENESIS; PHARMACOKINETICS;
D O I
10.1186/1475-2875-8-159
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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 asexual blood-stage parasites. A model of optimal timing suggests that primaquine follow-up approximately eight days after a clinical episode could further reduce the duration of infectiousness from two to four weeks down to a few days. The prospects of malaria elimination would be substantially improved by changing the timing of primaquine administration and combining this with effective detection and management of imported malaria cases. The value of using primaquine to reduce residual gametocyte densities and to reduce malaria transmission was considered in the context of a malaria transmission model; the added benefit of the primaquine follow-up treatment would be relatively large only if a high fraction of patients (>95%) are initially treated with schizonticidal agents. Conclusion: Mathematical models have previously identified the long duration of P. falciparum asexual blood-stage infections as a critical point in maintaining malaria transmission, but infectiousness can persist for two to four weeks because of residual populations of mature gametocytes. Simulations from new models suggest that, in areas where a large fraction of malaria cases are treated, curing the asexual parasitaemia in a primary infection, and curing mature gametocyte infections with an eight-day follow-up treatment with primaquine have approximately the same proportional effects on reducing the infectious period. Changing the timing of primaquine administration would, in all likelihood, interrupt transmission in this area with very good health systems and with very low endemicity.
引用
收藏
页数:13
相关论文
共 50 条
[1]   Dynamics of gametocytes among Plasmodium falciparum clones in natural infections in an area of highly seasonal transmission [J].
Abdel-Wahab, A ;
Abdel-Muhsin, AMA ;
Ali, E ;
Suleiman, S ;
Ahmed, S ;
Walliker, D ;
Babiker, HA .
JOURNAL OF INFECTIOUS DISEASES, 2002, 185 (12) :1838-1842
[2]   Dynamics of P-falciparum gametocytemia in symptomatic patients in an area of intense perennial transmission in Tanzania [J].
Akim, NIJ ;
Drakeley, C ;
Kingo, T ;
Simon, B ;
Senkoro, K ;
Sauerwein, RW .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2000, 63 (3-4) :199-203
[3]   Characteristics of Plasmodium falciparum parasites that survive the lengthy dry season in eastern Sudan where malaria transmission is markedly seasonal [J].
Babiker, HA ;
Abdel-Muhsin, ABA ;
Ranford-Cartwright, LC ;
Satti, G ;
Walliker, D .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1998, 59 (04) :582-590
[4]  
BANGCHANG KN, 1994, T ROY SOC TROP MED H, V88, P220, DOI 10.1016/0035-9203(94)90306-9
[5]   Population biology and antimalarial resistance:: The transmission of antimalarial drug resistance in Plasmodium falciparum [J].
Barnes, KI ;
White, NJ .
ACTA TROPICA, 2005, 94 (03) :230-240
[6]  
Breman JG, 2001, AM J TROP MED HYG, V64, P1
[7]  
Buchachart K., 2001, Southeast Asian Journal of Tropical Medicine and Public Health, V32, P720
[8]   Deployment of early diagnosis and mefloquine-artesunate treatment of falciparum malaria in Thailand: The Tak malaria initiative [J].
Carrara, Verena Ilona ;
Sirilak, Supakit ;
Thonglairuam, Janjira ;
Rojanawatsirivet, Chaiporn ;
Proux, Stephane ;
Gilbos, Valery ;
Brockman, Al ;
Ashley, Elizabeth A. ;
McGready, Rose ;
Krudsood, Srivicha ;
Leemingsawat, Somjai ;
Looareesuwan, Sornchai ;
Singhasivanon, Pratap ;
White, Nicholas ;
Nosten, Francois .
PLOS MEDICINE, 2006, 3 (06) :856-864
[9]   Transmission-blocking activities of quinine, primaquine, and artesunate [J].
Chotivanich, Kesinee ;
Sattabongkot, Jetsumon ;
Udomsangpetch, Rachanee ;
Looareesuwan, Sornchai ;
Day, Nicholas P. J. ;
Coleman, Russell E. ;
White, Nicholas J. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2006, 50 (06) :1927-1930
[10]   Modelling the transition of asexual blood stages of Plasmodium falciparum to gametocytes [J].
Diebner, HH ;
Eichner, M ;
Molineaux, L ;
Collins, WE ;
Jeffrey, GM ;
Dietz, K .
JOURNAL OF THEORETICAL BIOLOGY, 2000, 202 (02) :113-127