Biology Reference
In-Depth Information
option, and yet the task of developing new radical cures is essential. Sections
to follow in this chapter propose strategies for detecting and coping with the
far-reaching problem of resistance to chloroquine in vivax malaria chemo-
therapeutics.
4. CHEMOPROPHYLAXIS AGAINST VIVAX MALARIA
Travellers from non-endemic zones may use antimalarial drugs to
prevent acute malaria during and after the visit. The vast majority of these
drugs provide suppressive rather than causal prophylaxis, i.e. they kill blood
stages rather than liver stages. These drugs have no effect on latent hypnozo-
ites and travellers may be directed to consume PART upon completion of
travel in order to avoid relapse in the following weeks, months and years. In
reality, however, few begin or finish this treatment and late relapse following
exposure to endemic vivax malaria may be the rule with exclusive use of
suppressive chemoprophylactic drugs (
Swartz et al., 2003
).
Early clinical trials with primaquine (and a Russian primaquine-like
drug called quinocide) demonstrated causal prophylaxis against falciparum
and vivax malarias (
Baird et al., 2003
;
Lysenko, 1960
). In falciparum malaria,
a single 30 mg dose given within 48 h of sporozoite inoculation sufficed. In
other words, just 30 mg of primaquine was sufficient to kill the early devel-
oping forms of
P. falciparum
in hepatocytes. The same single-dose experi-
ment was not repeated for
P. vivax
, but 30 mg daily for 5 days also proved
effective against experimental challenge (
Baird et al., 2003
;
Arnold et al.,
1954
,
1955
;
Powell and Brewer, 1967
;
Alving et al., 1959
). As will be seen
later, the same regimen for preventing relapse after acute illness is almost
completely inefficacious: killing developed hypnozoites requires higher
doses than preventing their formation, which is presumably what causal
prophylaxis accomplishes.
During the era of drug development in the 1950s, chloroquine became
the universal choice for chemoprophylaxis by virtue of its superior safety,
tolerability and convenience compared to primaquine. Primaquine for pro-
phylaxis was not further pursued. Further, as chloroquine efficacy and utility
in chemoprophylaxis ebbed during the 1970s and 1980s, drug developers
naturally sought to replace it with other blood schizontocides. Suppressive
prophylaxis had come to be viewed as the favoured approach.
The US Navy conducted a series of clinical trials during the 1990s and
early 2000s that re-examined primaquine for causal prophylaxis. An early
trial, as a result of initial safety and tolerability concerns, applied a regimen
