Shmuklarsky M J, Boudreau E F, Pang L W, Smith J I, Schneider I, Fleckenstein L, Abdelrahim M M, Canfield C J, Schuster B
Department of Pharmacology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Ann Intern Med. 1994 Feb 15;120(4):294-9. doi: 10.7326/0003-4819-120-4-199402150-00006.
To determine whether doxycycline, 100 mg administered as a single daily oral dose, is effective as a causal prophylactic agent, an agent active against the pre-erythrocytic liver stage of Plasmodium falciparum malaria parasites, in healthy nonimmune persons. If effective, the recommendation by the Centers for Disease Control and Prevention (CDC) that doxycycline be continued for 4 weeks after returning from malaria-endemic areas could be shortened to 1 week.
Randomized, double-blind, placebo-controlled trial.
Medical ward at the U.S. Army Research Institute of Infectious Diseases, Fort Detrick, Maryland.
18 nonimmune, healthy, adult male volunteers, age 21.7 +/- 2.9 (SD) years, were enrolled in two groups, one of 8 persons and one of 10 persons. Six participants in the first group and 7 in the second group received doxycycline. The remaining participants received placebo. Two volunteers were dropped from the study, leaving 16 participants for analysis.
Each participant received doxycycline, 100 mg, or placebo in a single daily oral dose starting 3 days before exposure to P. falciparum-infected mosquitoes and ending 6 days after exposure.
Monitoring for parasitemia, plasma doxycycline concentrations, and mosquitoes' salivary-gland sporozoite grade.
6 of 6 (100% [95% Cl, 54% to 100%]) participants on doxycycline in the first group and 2 of 6 (33% [Cl, 4% to 78%]) in the second group were protected from malaria. No differences were found between protected and nonprotected participants in the doxycycline elimination half-life (T1/2) (20.8 +/- 5.0 h compared with 21.9 +/- 5.2 h), the steady-state average plasma concentration (1626 +/- 469 ng/mL compared with 1698 +/- 651 ng/mL), or other pharmacokinetic parameter estimates. The mean mosquito salivary-gland sporozoite grade was significantly higher (P = 0.02) in protected (3.5 +/- 0.3) than in nonprotected persons (3.1 +/- 0.1). Overall, 8 of 12 persons on doxycycline were protected from malaria, yielding a causal prophylactic efficacy rate of 67% (Cl, 35% to 90%).
A dosing regimen of doxycycline, 100 mg once daily, administered as a causal prophylactic agent against P. falciparum malaria in healthy, nonimmune volunteers, had an unacceptably high failure rate. Therefore, the CDC recommendation that doxycycline should be taken daily starting 1 to 2 days before travel, during travel, and for 4 weeks after travel should still be followed.
确定每日口服100毫克多西环素作为病因预防药物，对健康的非免疫人群中恶性疟原虫疟疾寄生虫的红细胞前期肝脏阶段是否有效。如果有效，疾病控制与预防中心（CDC）建议从疟疾流行地区返回后持续服用多西环素4周的时间可缩短至1周。
随机、双盲、安慰剂对照试验。
马里兰州德特里克堡美国陆军传染病研究所的医疗病房。
18名非免疫、健康的成年男性志愿者，年龄21.7±2.9（标准差）岁，分为两组，一组8人，一组10人。第一组的6名参与者和第二组的7名参与者接受多西环素治疗。其余参与者接受安慰剂。两名志愿者退出研究，剩余16名参与者进行分析。
每位参与者从暴露于感染恶性疟原虫的蚊子前3天开始，至暴露后6天结束，每日口服一次100毫克多西环素或安慰剂。
监测寄生虫血症、血浆多西环素浓度和蚊子唾液腺子孢子等级。
第一组中接受多西环素治疗的6名参与者中有6名（100%[95%可信区间，54%至100%]）受到疟疾保护，第二组中6名参与者中有2名（33%[可信区间，4%至78%]）受到保护。在多西环素消除半衰期（T1/2）（分别为20.8±5.0小时和21.9±5.2小时）、稳态平均血浆浓度（分别为1626±469纳克/毫升和1698±651纳克/毫升）或其他药代动力学参数估计值方面，受保护和未受保护的参与者之间未发现差异。受保护者（3.5±0.3）的平均蚊子唾液腺子孢子等级显著高于未受保护者（3.1±0.1）（P=0.02）。总体而言，12名服用多西环素的参与者中有8名受到疟疾保护，病因预防有效率为67%（可信区间，35%至90%）。
对于健康的非免疫志愿者，每日一次服用100毫克多西环素作为预防恶性疟原虫疟疾的病因预防药物，失败率高得令人无法接受。因此，仍应遵循CDC的建议，即在旅行前1至2天、旅行期间以及旅行后4周每天服用多西环素。
