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

REVIEW / 29
operational conditions govern further spread and must be taken
into consideration in attempt ing to forecast such spread. Where
falciparum malaria is being contained and reduced by measures
directed against transmission, namely anti-vector and antigametocyte
measures, then it may be assumed that drug-sensitive
and resistant strains will be equally inhibited. In contrast,
where falciparum malaria is spreading, there is every indication
that chloroquine-sensitive strains are gradually being replaced by
chloroquine-resistant strains. Progressive movement of resistant
parasites is historically apparent in South-East Asia, as they
have spread during the past 20-25 years through much of the Region
from their point of emergence at the Thai-Kampuchean border.
Trends in the Spread of Resistance Westwards in Asia
It is reasonable to project this historical spread beyond
1980 along the lines of flow that may be expected on the basis of
general increases in P. falciparum incidence 1n receptive areas,
particularly those visited by migrants carrying resistant gametocytes.
In the past two years resistant strains of P.falciparum
have continued to replace sensitive strains in Burma, eastern
Bangladesh and north-east India; foci have been identified more
or less sequentially across central India (see page 14) and this
progression may be expected to continue in the direction of
Rajasthan and Pakistan rather than southwards where the prevalence
of P.falciparum is slight.
Similarly, the degree of resistance has increased, with a
shift occurring from RI towards RIll as resistant strains become
more prevalent. It appears that the periphery of a zone of
resistance is composed of RI and S grades, both of which are
carried to the adjacent susceptible-grade zones where they
hybridize with the indigenous S-strains and, if conditions are
favourable, give rise to RI foci. Meanwhile, the central part of
a zone of resistance will have lost its S-strains through
hybridization or overgrowth, and continual hybridization among the
concentrating R gametocytes progressively shifts the grade towards
RIll. Intermediate zones between the periphery and the centre are
occupied mainly by RI and some RII, with a small residue of S on
the verge of extinction. Such free hybridization occurs because
several strains of parsite may coexist in an individual host, all
producing gametocytes picked up together by a feeding mosquito.
In vitro Predictors
In vitro testing affords a more comprehensive measurement of
the spread and degree of resistance than in vivo testing. If on
the periphery of the advancing wave of resistance there are areas
where the degree of susceptibility of the paras ite is decreasing,
but has not yet reached RI,this should be identifiable by in vivo