Biology Reference
In-Depth Information
along with pamaquine, pentaquine, isopentaquine, and primaquine hyp-
nozoitocides. The investigators close their report by writing, '…
with respect
to the major features of disease and responses to standard chemotherapeutic agents,
infections with sporozoites and trophozoites of P. cynomolgi in rhesus monkeys are
remarkably similar to infections with New Guinea Chesson strain of P. vivax in
human volunteers. Infections with these strains are not identical in every respect.
They are sufficiently alike, however, to give strong support to the use of the P. cyno-
molgi-rhesus monkey model in the search for improved prophylactic, radical curative,
and suppressive drugs
'.
This superb model, however, has not been widely applied in evaluat-
ing blood schizontocides for potential use in humans. Instead, what typi-
cally occurs is the development and licensure of drugs for acute falciparum
malaria being evaluated against
P. vivax
in patients. This has been the case
with mefloquine, atovaquone-proguanil, and each of the ACTs as they
matured in development. That approach, pragmatic as it may be, will miss
partnering with primaquine or some other hypnozoitocide for demonstra-
tion of the safety and efficacy of the radical cure required against vivax
malaria in the real world. As the extensive independent work of Schmidt
and Rossan demonstrated, this animal model may offer a practical means
of evaluating blood schizontocide-hypnozoitocide partners prior to use in
relatively more costly and risky clinical trials.
8.3. Primaquine
8.3.1. In vivo
High rates of
P. vivax
recurrence have been observed following primaquine
therapy, but there is no standardized means of affirming resistance in such
patients. The existence of truly primaquine-resistant hypnozoites has never
been unequivocally demonstrated (
Galappaththy et al., 2007
;
Goller et al.,
2007
). Measuring the therapeutic response to primaquine is by no means
impossible, and in infected travellers returned to non-endemic zones, rela-
tively straightforward. The difference between great difficulty and relative ease
is confounding by risk of reinfection. Reinfection represents the primary
obstacle in assessing the therapeutic response to primaquine. Relapse and
reinfection may each occur during the necessary months of post-treatment
follow up. Unlike
P. falciparum
, where reinfection and recrudescence repre-
sent the relatively easily distinguished possible sources of new parasitaemia,
the hypnozoite of
P. vivax
imposes complexity and ambiguity. The limita-
tions with molecular genotyping as a tool of discernment have already been
explained in this chapter.
