Assessment of Long-Term Health Effects of Antimalarial Drugs When Used for Prophylaxis (2020)
Chapter: Appendix C: Epidemiologic Studies That Met the Committee's Inclusion Criteria
| Reference | Design | Population | Study Groups‡ | Body Systems Examined |
|---|---|---|---|---|
| Ackert et al., 2019* | Randomized controlled trial | Healthy male and female adult volunteers (ages 18–45) in the United States | Tafenoquine (n = 306) Placebo (n = 161) | Eye |
| Andersen et al., 1998 | Randomized controlled trial | Semi-immune male and female adult volunteers (ages 18–55) in Kenya |
Doxycycline (n = 55) Azithromycin (n = 117) 250 mg daily (n = 59) Placebo (n = 60) |
Other |
| DeSouza, 1983 | Clinical trial | Healthy male adult volunteers (age range not reported) in Brazil | Mefloquine 1,000 mg (n = 10) Sulfadoxine (1,000 mg) and pyrimethamine (500 mg) (n = 10) |
Gastrointestinal Cardiovascular |
| Eick-Cost et al., 2017* | Retrospective observational study | Male and female active-duty U.S. service members (ages ≥17) |
Deployed (n = 275,097)
Mefloquine (n = 25,691) Nondeployed (n = 92,743) Mefloquine (n = 10,847) |
Neurologic Psychiatric |
| Green et al., 2014* | Randomized controlled trial | Healthy male and female adult volunteers (ages 18–65) in the United States |
Tafenoquine (n = 156)
Supratherapeutic dose of 1,200 mg (n = 52) Moxifloxacin (400 mg) (n = 52) Placebo (n = 52) |
Cardiovascular |
| Laothavorn et al., 1992 | Prospective observational study | Male patients with malaria and healthy male adult volunteers (ages 26–46) in Thailand | Mefloquine (750 mg) (n = 18) Patients with malaria (n = 102) |
Cardiovascular |
| Leary et al., 2009* | Randomized controlled trial | Healthy male and female adult volunteers (ages 18–55) recruited from the United States and the United Kingdom | Tafenoquine (n = 81) Placebo (n = 39) |
Eye Other |
| Lee et al., 2013 | Cross-sectional survey | Current and former male and female adult members of the Australian Federal Police Association (ages 35–45) | Doxycycline (n = 189) Deployed (n = 171) Nondeployed (n = 18) |
Gastrointestinal |
| Lege-Oguntoye et al., 1990 | Randomized controlled trial | Semi-immune male and female adult volunteers (ages 25–34) in Nigeria | Chloroquine (n = 20) Ascorbic acid (200 mg) (n = 10) |
Other |
| Meier et al., 2004* | Retrospective observational study | Male and female adult travelers (ages 17–79) in the United Kingdom | Mefloquine (n = 16,491) Doxycycline (n = 4,574) Proguanil and/or chloroquine (n = 16,129) |
Neurologic Psychiatric Eye |
| Miller et al., 2013 | Randomized controlled trial | Healthy male and female adult volunteers (ages 18–55) in the United States | Chloroquine (600 mg) and placebo for tafenoquine (n = 20) Placebo for chloroquine and tafenoquine (450 mg) (n = 20) Chloroquine (600 mg) and tafenoquine (450 mg) (n = 20) |
Eye Other |
| Nasveld et al., 2010* | Randomized controlled trial | Healthy male and female Australian soldiers (ages 18–55) | Mefloquine followed by primaquine (30 mg) (n = 162) Tafenoquine followed by placebo (n = 492) |
Psychiatric Gastrointestinal Eye Cardiovascular Other |
| Reference | Design | Population | Study Groups‡ | Body Systems Examined |
|---|---|---|---|---|
| Rueangweerayut et al., 2017 | Prospective observational study | Healthy female adult volunteers (ages 18–45) in Thailand |
Tafenoquine (n = 51)
100 mg (n = 12) Primaquine (n = 11) |
Other |
| Schlagenhauf et al., 1996† | Prospective observational study | Healthy male and female adult Swiss travelers (ages 18–65) | Mefloquine (n = 394) | Neurologic Psychiatric |
| Schneider et al., 2013* | Retrospective observational study | Male and female travelers (ages ≥1) from the United Kingdom | Mefloquine (n = 10,169) A/P (n = 28,502) Chloroquine and/or proguanil (n = 2,904) Unexposed (n = 41,573) |
Neurologic Psychiatric |
| Schneider et al., 2014* | Retrospective observational study | Male and female travelers (ages ≥1) from the United Kingdom | Mefloquine (n = 10,169) A/P (n = 28,502) Chloroquine and/or proguanil (n = 2,904) Unexposed (n = 41,573) |
Eye |
| Schneiderman et al., 2018* | Cross-sectional survey | Post 9/11 male and female U.S. military veterans (ages ≥24) |
Deployed (n = 12,456)
No antimalarial use (n = 5,806) Nondeployed (n = 7,031) No antimalarial use (n = 5,294) |
Psychiatric |
|
Chloroquine (n = 110) |
||||
| Schwartz and Regev-Yochay, 1999 | Prospective observational study | Non-immune adult Israeli travelers (ages 22–65) (sex distribution not reported) |
Mefloquine (n = 25) Doxycycline (n = 19) Primaquine (n = 106) 15 mg daily for individuals with a body weight of <70 kg Hydroxychloroquine (200 mg) (n = 8) |
Unknown |
| Tan et al., 2017 | Cross-sectional survey | Male and female returned U.S. Peace Corps volunteers (age range not reported) | Mefloquine (n = 2,981) A/P (n = 183) Doxycycline (n = 831) Chloroquine (n = 674) Other prophylactic medication (n = 386) No antimalarial use (n = 3,876) |
Neurologic Psychiatric Gastrointestinal Eye Cardiovascular Other |
| Walsh et al., 2004 | Randomized controlled trial | Thai soldiers (ages 18–55) (sex distribution not reported) |
Tafenoquine (n = 104)
400 mg for 3 consecutive days, followed by 400 mg once monthly Placebo (n = 101) |
Other |
| Reference | Design | Population | Study Groups‡ | Body Systems Examined |
|---|---|---|---|---|
| Wells et al., 2006* | Retrospective observational study | Male and female U.S. active-duty service members (ages ≥17) |
Mefloquine (n = 8,858)
U.S. active-duty service members prescribed at least seven tablets of mefloquine and deployed to operational theater or combat zone No antimalarial drug use U.S. active-duty service members assigned to Europe or Japan (n = 156,203) |
Neurologic Psychiatric Gastrointestinal Cardiovascular Other |
* Denotes epidemiologic studies considered to provide the most contributory evidence to address the committee’s charge.
† Although study investigators did not make a traditional comparison between exposed and unexposed groups, they did compare individuals who experienced adverse events with those who did not experience adverse events in the data analysis; thus, the committee included this study in their evaluation of the available scientific evidence.
‡ For the six antimalarial drugs of interest the dosing regimen used follows standard FDA guidance unless otherwise noted.
