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

80 / RESEARCH FOR CONTROL
association with chemotherapy, can only be determined by a careful
malariological field study of each situation following which a
plan of action can be "tailor-made" to fit the epidemiological
circumstances and the potential of the local health authorities.
A change of policy regarding the use of chloroquine (or
sulfadoxine/pyrimethamine), particularly at a peripheral health
service level, when resistance emerges, is a particularly
difficult question on which no blanket recommendation can be
made. Appropriate investigations should be carried out in the
field to determine at what level of resistance a drug should be
withdrawn and replaced by an alternative drug if, indeed, for
practical reasons, it is at all possible to withdraw it. For
example, chloroquine may still be essential to relieve symptoms or
even be life-saving, despite a moderate, yet well established
level of resistance in a particular area. It may also not be
possible or desirable to replace completely chloroquine with
su1fadoxine/pyrimethamine for presumptive treatment. A further
problem arises in areas where a significant degree of resistance
has emerged also to sulfadoxine/pyrimethamine.
Research is needed to determine the part that drugs should
play in relation to other control measures, for example in the
elimination of isolated foci of resistant parasites.
Whi le experimental and ep idemiolog ical evidence sugges t s that
chloroquine resistance is a highly stable, if not a dominant
character of p.falciparum, no data exist to show whether parasites
could revert to normal sensitivity if drug selection pressure were
to be totally withdrawn for a period of time. Field studies to
determine this could be established, e.g. in island populations.
No data are available from the field on the possible
influence of the alternation of drugs on the development of drug
resistance. Both retrospective and prospective studies are
required on this question.
Factors Related to Clinical Pharmacology
optimal dosage schedules of available drugs
value of drug combination
clinical trials of new drugs
Certain questions still remain concerning the use of existing
drugs, e.g. the optimal dosage of chloroquine for presumptive
treatment, dosage and timing of primaquine administration as a
gametocytocide. These should be addressed in appropriate field
research projects.
In the course of the development of new drug formulations,
drug combinations or entirely new drugs, there comes a time when
the preparation, having passed the hurdles of pre-c1inica1 studies