| dc.description.abstract | Malaria is one of the major global health problems with high mortality rates especially in
children below five- years of age. The interventions in place to control the disease
worldwide include vector control and chemotherapy. Chemotherapy has developed
crippling limitations due to malaria drug resistance to the effective, available and
affordable anti-malarials. The emergence of parasite resistance has limited the armory of
effective anti-malarials. Resistance is developing faster than the development of new and
effective anti-malarials. This has raised a need of therapy optimization using the already
existing anti-malarials. Combination therapy has been shown to effectively delay the
onset of resistance and improve the efficacy of two or more anti-malarials when in
combination. The objective of this study was to establish the activity of cAMP
modulators on a few selected anti-malarials in vitro. The cAMP modulators were tested
in combination with chloroquine, quinine, mefloquine, amodiaquine and doxycycline
against Plasmodium falciparum in vitro against chloroquine sensitive strain (D6) and the
chloroquine resistant strain (W2). Parasite susceptibility testing was carried out using
semi automated micro dilution technique. The Inhibitory Concentration at 50% (ICso)
was calculated for each drug and for the drugs in fixed combination (1:1, 1:3, 3:1, 1:4,
4:1, 1:5). These data were used to calculate the Fractional Inhibitory Concentration at
50% (FICso) and to plot isobolograms. Quinine-AC inhibitors combination assays
showed synergistic interactions in all the levels of concentration ratios against both the
D6 and W2. The other anti-malarials-AC inhibitor combination assays showed a range of
response, additivity, synergism and antagonism at different levels of concentration ratios.
Anti-malarials-AC activators mainly exhibited antagonistic interactions. These fmdings
suggest that quinine-AC inhibitors combination should be considered for evaluation as
possible new anti-malarial combinations. | en_US |
