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

56 / RESEARCH RESULTS
EXO-ERYTHROCYTIC DEVELOPMENT OF MALARIA PARASITES
The hypnozoite stage of parasite development was recently
discovered with a fluorescent antibody technique in sections of
liver from rhesus monkeys infected with ~'y'nomolgi. It 1S a
single cell liver stage which is thought to be a dormant precursor
of tissue schizonts responsible for relapses in this and simi lar
infections such as P.vivax. Hypnozoites have been found in
retrospective examinat10ns of liver sections from chimpanzees
infected with P.vivax. While more information is needed,
knowledge of the hypnozoite may help to understand better the
phenomenon of relapses and the mode of action of antirelapse
drugs. Experimental evidence with P.simiovale, P.cynomolgi and
P.vi~ suggests that the ability ofa particular sporozoite to
cause a primary attack, an early or late relapse may be genetically
predetermined. At present, the 8-aminoquinolines (e.g.
primaquine) are the only group of drugs available to prevent
relapses. Primaquine probably clears hypnozoites but, as yet,
dose relationships are not known. Primaquine has a sporontocidal
action as well. However, it is difficult to relate the dose
levels required for sporontocidal action to those needed for
preventing relapses.
It is quite possible that a screening model for
gametocytocidal activity (e.g. Haemoproteus) could also be used
for finding new antirelapse drugs which are effective against
hypnozoites.
CHLOROQUINE RETINOPATHY
It 1S difficult to distinguish between chloroquine specific
and other types of retinopathy. In susceptible individuals the
defic iency of sphingomyelinase or other lysosomal enzyme systems
could cause the development of this toxic manifestation 1n a
shorter period of time. This fact could explain isolated reports
of rapidly developing retinopathy. Retinopathy is known to
develop rather fast in patients taking high daily doses of
chloroquine, e.g. for the treatment of collagenoses. With regard
to chloroquine for malaria chemoprophylaxis, there are several
extended studies in large populations which were exposed to a
prolonged use of this drug either in the form of tablets or as
medicated salt. No retinopathy has been observed 1n these
groups. Chloroquine ret inopathy is time and dose dependent. It
is generally accepted that chloroquine retinopathy very rarely
occurs under routine chemoprophylaxis at total cumulative doses of
less than 100 g base. In most persons, retinopathy will not
develop even after an intake of more than 100 g (base).
CLINICAL PHARMACOLOGICAL STUDIES
The importance of pharmacodynamic and pharmacokinet ic factors
1n relation to the efficacy of particular drugs and dose regimens