Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study

被引:146
作者
Schlagenhauf, P [1 ]
Tschopp, A
Johnson, R
Nothdurft, HD
Beck, B
Schwartz, E
Herold, M
Krebs, B
Veit, O
Allwinn, R
Steffen, R
机构
[1] Univ Zurich, Inst Social & Prevent Med, Div Epidemiol & Communicable Dis, CH-8006 Zurich, Switzerland
[2] Univ Zurich, Inst Social & Prevent Med, Dept Biostat, CH-8006 Zurich, Switzerland
[3] USA, Environm Med Res Inst, Mil Performance Div, Natick, MA 01760 USA
[4] Univ Munich, Dept Trop Med & Infect Dis, D-80539 Munich, Germany
[5] Swiss Trop Inst, CH-4002 Basel, Switzerland
[6] Tel Aviv Univ, IL-69978 Tel Aviv, Israel
[7] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel
[8] Goethe Univ Frankfurt, Inst Med Virol, D-6000 Frankfurt, Germany
来源
BMJ-BRITISH MEDICAL JOURNAL | 2003年 / 327卷 / 7423期
关键词
D O I
10.1136/bmj.327.7423.1078
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective To compare the tolerability of malaria chemoprophylaxis regimens in non-immune travellers. Design Randomised, double blind, study with placebo run-in phase. Setting Travel clinics in Switzerland, Germany, and Israel. Main outcome measure Proportion of participants in each treatment arm with subjectively moderate or severe adverse events. Participants 623 non-immune travellers to sub-Saharan Africa: 153 each received either doxycycline, mefloquine, or the fixed combination chloroquine and proguanil, and 164 received the fixed combination atovaquone and proguanil. Results A high proportion of patients reported adverse events, even in the initial placebo group. No events were serious. The chloroquine and proguanil arm had the highest proportion of mild to moderate adverse events (69/153; 45%, 95% confidence interval 37% to 53%) followed by mefloquine (64/153; 42%, 34% to 50%), doxycycline (51/153; 33%, 26% to 41%), and atovaquone and proguanil (53/164; 32%, 25% to 40%) (P=0.048 for all). The mefloquine and combined chloroquine and proguanil arms had the highest proportion of more severe events (n=19; 12%, 7% to 18%) and (n=16; 11%, 61% to 15%, respectively), Whereas the combined atovaquone and proguanil and doxycycline arms had the lowest (n=11; 7%, 2% to 11% and n=9; 6%, 2% to 10%, respectively: P=0.137 for all). The mefloquine arm had the highest proportion of moderate to severe neuropsychological adverse events, particularly in Women (n=56; 37%, 29% to 44% versus chloroquine and proguanil, n=46; 30%, 23% to 37%; doxycycline, n=36; 24%,17% to 30%; and atovaquone and proguanil, n=32; 20%, 13% to 26%: P=0.003 for all). The highest proportion of moderate or severe skin problems were reported in the chloroquine and proguanil arm (n=12; 8%, 4% to 13% versus doxycycline, n=5; 3%, 1% to 6%; atovaquone and proguanil, n=4; 2%, 0% to 5%; mefloquine, n=2; 1%, 0% to 3%: P=0.013). Conclusions Combined atovaquone and proguanil and doxycyline are well tolerated antimalarial drugs. Broader experience with both agents is needed to accumulate reports of rare adverse events.
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页码:1078 / +
页数:8
相关论文
共 27 条
[1]   Successful double-blinded, randomized, placebo-controlled field trial of azithromycin and doxycycline as prophylaxis for malaria in western Kenya [J].
Andersen, SL ;
Oloo, AJ ;
Gordon, DM ;
Ragama, OB ;
Aleman, GM ;
Berman, JD ;
Tang, DB ;
Dunne, MW ;
Shanks, GD .
CLINICAL INFECTIOUS DISEASES, 1998, 26 (01) :146-150
[2]   A COMPARATIVE-STUDY OF GASTROINTESTINAL INFECTIONS IN UNITED-STATES SOLDIERS RECEIVING DOXYCYCLINE OR MEFLOQUINE FOR MALARIA PROPHYLAXIS [J].
ARTHUR, JD ;
ECHEVERRIA, P ;
SHANKS, GD ;
KARWACKI, J ;
BODHIDATTA, L ;
BROWN, JE .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1990, 43 (06) :608-613
[3]  
Barrett PJ, 1996, BRIT MED J, V313, P525, DOI 10.1136/bmj.313.7056.525
[4]  
BOUDREAU E, 1993, TROP MED PARASITOL, V44, P257
[5]  
Bradley D J, 2001, Commun Dis Public Health, V4, P84
[6]  
*CDC, 2001, HLTH INF INT TRAV
[7]  
*COMM ADV TROP MED, 2001, CAN REC PREV TREATM
[8]  
CROFT AM, 2001, COCHRANE DATABASE SY, P138
[9]  
CROFT AM, 2001, COCHRANE DB SYST REV, V1, P138
[10]   Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune travellers:: a randomised, double-blind study [J].
Hogh, B ;
Clarke, PD ;
Camus, D ;
Nothdurft, HD ;
Overbosch, D ;
Günther, M ;
Joubert, I ;
Kain, KC ;
Shaw, D ;
Roskell, NS ;
Chulay, JD .
LANCET, 2000, 356 (9245) :1888-1894