Drug-Resistant Malaria - libdoc.who.int - World Health Organization

64 / CONTROL
may develop from any surviving individual asexual forms. When any
of these compounds are used for the treatment of established
infections (in practice this will usually only refer to
chloroquine), far larger numbers of asexual parasites will be
exposed to them. Ultimately the number of parasites exposed to a
drug is the product of the number of people taking the drug
multiplied by the mean number of parasites per individual.
Frequency of Resultant Mutants in Parasite Populations
Various estimates have been made of the frequency with which
mutants resistant to various antimalarial drugs occur in different
species of malaria parasites of birds and of rodents, but no good
estimates are available for P.falciparum. While the frequency of
mutations resulting in parasites resistant to DHFR inhibitors
appears to be greater than that for chloroquine, this depends very
much on the parasite species. Estimates for pyrimethamine seem to
su§gest that resistant mutants are present in the order of 1 in
10 parasites or less in natural populations of both
P.gallinaceum and P.falciparum. While no estimate is available
for chloroquine, the relative frequencies would appear to be
P.berghei > P.falciparum>,,>P.gallinaceum»P.vivax. Moreover, there
seems to be a geographical variation in the mutation rate in
P. falciparum as regards resistance to chloroquine, the rate being
apparently higher in South-East Asia and South America than 1n
Africa. However, host as well as parasite factors must play a
role in the ease of manifestat ion of chloroquine resistance, and
this may well account for the long delay before this phenomenon
has become apparent on the African continent.
Influence of Drugs on Parasite Transmission
While antifols have a sporontocidal action against drugsensitive
strains of P.falciparum, this "action is lost in parallel
with decreasing sensitivity of the asexual stages. Chloroquine
which has neither a sporontocidal action nor any action against
mature gametocytes even of drug-sensitive strains of P.falciparum,
appears to have a paradoxical action on the transmission of
chloroquine-resis.ant parasites, and may actually enhance their
infec t i vity to vec tor anophe lines. However, this may be re lated
to the biological advantage of chloroquine-resistant P.falciparum.
Primaquine which is, of course, not used for the prophylaxis or
therapy of falciparum malaria, possesses a potent gametocytocidal
action against both chloroquine or antifol-sensitive or -resistant
parasites.
Antimalarial Drugs Available and Their Roles
Table 8 shows drugs or combinations 1n current use (see
Appendix 5 for further details)