Table 3.
Characteristics of the studies with circumstantial pharmacological evidence in support of a short post-travel regimen.
| Author, year of publication, country | Study design | Number of participants | Studied antimalarial agent | Measure of outcome and results |
|---|---|---|---|---|
| Butcher et al., 2003 [47] Department of Biologic Sciences, Imperial College of Science Technology and Medicine, London |
Non-clinical experimental (i.e. serological) study with P. falciparum transmission and asexual experiments by feeding mosquitoes AP treated sera | 3 AP treated subjects were bled for sera on day 0, 7, 14, 21, 28, 42, and 56. 2 atovaquone only treated subjects were bled for sera on day 0, 7, 14, 21, 28 or 35, and 42 or 49. |
AP treatment with 1000/400 mg daily for 3 days on day 0. Secondly, 2 volunteers were treated with atovaquone only at a dosage equivalent to that of AP taken on day 0. | Transmission inhibition: sera 4–28 days after AP treatment totally blocked infection of the mosquitoes, and significant inhibition of oocyst development (P = .05) was still present at day 42 (mean: 12.5% SEM ± 1.94, of day 0 value). Asexual stage inhibition: sera inhibitory up to day 28: mean 11.4% (SEM ± 0.3) of growth compared to day 0 sera (P = .05). On day 42, the mean parasitaemia still was only 43.9% (SEM ± 17.7) of the day 0 value. |
| Butcher et al., 2000 [49] Department of Biologic Sciences, Imperial College of Science Technology and Medicine, London |
Non-clinical experimental (i.e. serological) study with P. berghei transmission and asexual experiments by feeding mosquitoes AP treated sera | 4 AP treated subjects were bled for sera on day 0 and subsequently for up to 10 weeks. 3 atovaquone or proguanil only subjects were bled for sera accordingly. |
AP treatment with 1000/400 mg daily for 3 days on day 0. Secondly, 3 volunteers were treated with atovaquone or proguanil only at a dosage equivalent to that of AP taken on day 0. |
Gametocyte-oocyst development tested at a dilution of 1:100 was totally inhibitory up to day 14 but varied from 0 to 100% [with a mean (S.E.) percentage of 43 (29.7)] on day 21. At day 56 there was no significant difference compared to the day-0 level. Gametocyte-ookinete development on days 3, 7, 14 and > 14 and tested at a dilution of 1:100 was 50%, 68%, 84% and 100% of the day-0 levels, respectively. Ookinete-oocyst development on days 3, 7, 14, 21, and 56 tested at a dilution of 1:100 was 4%, 8%, 33%, 25% and 100% of the day-0 levels, respectively. Asexual stage: on day 7 there was a 26-fold decrease in schizonts. Further data was not available. |
| Enosse et al., 2000 [48] United Kingdom and Matola, Mozambique |
Non-clinical, randomized, experimental (i.e. serological) study with P. falciparum and P. berghei transmission and asexual experiments by feeding mosquitoes AP treated sera | Field studies on P. falciparum infectivity: 33 AP treated subjects in Matola were bled for sera on day 0, 4, 7, 14, and 21. P. berghei infectivity: 4 AP treated British subjects were bled for sera on day 0 and subsequently for up to 12 weeks. |
AP treatment with 1000/400 mg daily for 3 days on day 0 vs. chloroquine. | Field studies on P. falciparum infectivity: asexual stages declined to 0 on day 4 in 14/15 subjects, 0 on day 14 for 26 subjects, and became positive on day 21 for 2/16 subjects. Gametocyte numbers in AP treated subjects declined on day 4, 7, 14, and 21–68%, 31%, 4%, and 0%, respectively. The oocysts declined to 30% on day 4, 0% on day 7, and rose to 30% on day 21. The mean prevalence of infected mosquitos was 20%, 1%, 0%, 2%, and 3% on day 0, 4, 7, 14, and 21, respectively. P. berghei infectivity: infectivity in AP treated subjects, tested at a 1:100 dilution, was completely inhibited up to day 28 with significant inhibition still present at day 42 and 56 (P = .03), namely 19% and 10%, respectively. |
AP, atovaquone-proguanil; SEM, mean expressed as a percentage of mean pretreatment day 0 sera; S.E., standard error.