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IN-VITRO SENSITIVITY OF PLASMODIUM FALCIPARUM TO CHLOROQUINE, HALOFANTRINE, MEFLOQUINE AND QUININE IN MADAGASCAR
Abstract
Objective: To determine how sensitive Plasmodium falciparum is to the major antimalarial
drugs in Madagascar.
Design: Assessment of Plasmodium falciparum isolates sensitivity to antimalarials, by
use of the in-vitro radioisotope method.
Setting: Ankazobe and Saharevo in the foothill areas; and Toamasina and Tolagnaro
in the coastal areas (between January 1998 and November 1999).
Subjects: Primary Plasmodium falciparum isolates from patients with uncomplicated
malaria attack.
Results: Between January 1998 and November 1999, of the 293 in-vitro tests done with
at least one antimalarial, 70% (205/293) were interpretable. As there was no significant
difference between results from the four study sites, the data have been expressed as
a whole. All of the successfully tested isolates were sensitive to halofantrine (n = 56)
and to quinine (n = 199), 5.8% (12/205) of the isolates were resistant to chloroquine
and 2% (4/199) to mefloquine. The geometric mean IC50 was 0.3 µg/L for halofantrine
(95% CI = 0.1 - 0.4 µg/L); 9.4 µg/L for chloroquine (95% CI = 7.3 - 10.8 µg/L); 3.8
µg/L for mefloquine (95% CI = 3.3 - 4.3 µg/L); and 26.8 µg/L for quinine (95% CI
= 24.3 - 29.4 µg/L). The low positive correlation found between halofantrine and
chloroquine IC50s (n=56; r = 0.41, P = 0.002) suggests a risk of cross-resistance between
these two drugs.
Conclusion: The degree and frequency of chloroquine resistance in-vitro is stationary
in Madagascar compared to previous results during the last decade. The in-vitro
sensitivity of P. falciparum to quinine, mefloquine and halofantrine encourages the use
of these drugs as alternative in case of chloroquine treatment failure. Nevertheless, it
is important to maintain and to extend malaria and drug sensitivity surveillance in
Madagascar.
drugs in Madagascar.
Design: Assessment of Plasmodium falciparum isolates sensitivity to antimalarials, by
use of the in-vitro radioisotope method.
Setting: Ankazobe and Saharevo in the foothill areas; and Toamasina and Tolagnaro
in the coastal areas (between January 1998 and November 1999).
Subjects: Primary Plasmodium falciparum isolates from patients with uncomplicated
malaria attack.
Results: Between January 1998 and November 1999, of the 293 in-vitro tests done with
at least one antimalarial, 70% (205/293) were interpretable. As there was no significant
difference between results from the four study sites, the data have been expressed as
a whole. All of the successfully tested isolates were sensitive to halofantrine (n = 56)
and to quinine (n = 199), 5.8% (12/205) of the isolates were resistant to chloroquine
and 2% (4/199) to mefloquine. The geometric mean IC50 was 0.3 µg/L for halofantrine
(95% CI = 0.1 - 0.4 µg/L); 9.4 µg/L for chloroquine (95% CI = 7.3 - 10.8 µg/L); 3.8
µg/L for mefloquine (95% CI = 3.3 - 4.3 µg/L); and 26.8 µg/L for quinine (95% CI
= 24.3 - 29.4 µg/L). The low positive correlation found between halofantrine and
chloroquine IC50s (n=56; r = 0.41, P = 0.002) suggests a risk of cross-resistance between
these two drugs.
Conclusion: The degree and frequency of chloroquine resistance in-vitro is stationary
in Madagascar compared to previous results during the last decade. The in-vitro
sensitivity of P. falciparum to quinine, mefloquine and halofantrine encourages the use
of these drugs as alternative in case of chloroquine treatment failure. Nevertheless, it
is important to maintain and to extend malaria and drug sensitivity surveillance in
Madagascar.
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