van Genderen Perry J J, Koene Henk R A, Spong Kimberly, Overbosch David
Department of Internal Medicine, Havenziekenhuis and Institute for Tropical Diseases, The Netherlands.
J Travel Med. 2007 Mar-Apr;14(2):92-5. doi: 10.1111/j.1708-8305.2007.00116.x.
In Europe, atovaquone/proguanil (A/P) is only licensed for malaria prophylaxis for 28 days of travel. Data on the long-term safety and tolerance in nonimmune travelers are scarce.
We initiated a prospective observational study on ailments reported by travelers using A/P on a long-term basis. Ailments were recorded on a regular questionnaire. Travelers rated their ailments as (1) mild, not interfering with their daily activities; (2) moderate, causing interference with daily activities; or (3) severe, resulting in a visit to a doctor or clinic.
One hundred sixty-nine subjects used A/P for a total of 2.974 weeks. One hundred fifty-three (90.5%) traveled to malaria-endemic regions in Africa. Seventy-five (44%) travelers, who used A/P for 1.140 weeks, reported no ailments. Ninety-four (56%) subjects who used A/P for 1.834 weeks reported a total of 363 ailments. Diarrhea was the most common ailment (13.5%; graded as mild in 7.2%, moderate in 4.7%, severe in 1.7%). Further complaints were headache (7.4%), malaise (6.1%), insomnia (5.2%), abdominal pain (5.0%), nausea (5.0%), and oral ulcers (4.1%). Four (2.4%) subjects discontinued prophylaxis due to complaints. No patient was admitted. Five (3.0%) cases of malaria were reported.
In our observational study encompassing more than 57 person-years of follow-up, A/P was tolerated well when taken longer than the current recommendation of 28 days of travel. Treatment-limiting ailments resulting in discontinuation of chemoprophylaxis were observed in 4 of 169 (2.4%) participants, whereas none of them was admitted. There were five (3.0%) cases of self-reported malaria. These observations suggest that A/P is also a safe and efficacious drug for the long-term chemoprophylaxis of falciparum malaria.
在欧洲，阿托伐醌/氯胍（A/P）仅被批准用于疟疾预防，适用于为期28天的旅行。关于非免疫旅行者长期安全性和耐受性的数据很少。
我们启动了一项前瞻性观察性研究，针对长期使用A/P的旅行者报告的疾病情况进行研究。通过定期问卷记录疾病情况。旅行者将他们的疾病评为：（1）轻度，不干扰日常活动；（2）中度，干扰日常活动；或（3）重度，导致去看医生或诊所。
169名受试者共使用A/P 2974周。其中153人（90.5%）前往非洲疟疾流行地区。75名（44%）使用A/P 1140周的旅行者报告无疾病。94名（56%）使用A/P 1834周的受试者共报告了363种疾病。腹泻是最常见的疾病（13.5%；轻度占7.2%，中度占4.7%，重度占1.7%）。其他症状包括头痛（7.4%）、不适（6.1%）、失眠（5.2%）、腹痛（5.0%）、恶心（5.0%）和口腔溃疡（4.1%）。4名（2.4%）受试者因不适而停止预防用药。无人住院。报告了5例（3.0%）疟疾病例。
在我们这项涵盖超过57人年随访的观察性研究中，当A/P的使用时间超过目前推荐的28天旅行期限时，耐受性良好。169名参与者中有4名（2.4%）出现导致停止化学预防的限制治疗的疾病，但无人住院。有5例（3.0%）自我报告的疟疾病例。这些观察结果表明，A/P也是一种用于恶性疟原虫长期化学预防的安全有效的药物。
