Biology Reference
In-Depth Information
prevent a great deal of mortality but did nothing to stop vivax relapses thus
discrediting the drug for a purpose it could not achieve (
Snowden, 2006
).
Quinine cured some persons of falciparum but not vivax and failed to stop
transmission. A single drug program in the absence of broader forms of
medical care and other means to reduce poverty such as improved housing
did not eliminate malaria and warns against a single intervention based only
on medication in an impoverished population with minimal health services
against a parasite capable of an evolutionary response.
3.3. Primaquine and Other 8-Aminoquinolines
As 8-aminoquinolines kill all stages of the malaria parasite, they are particu-
larly well-suited for malaria elimination efforts. Unfortunately, the entire
class of compounds also has characteristics that have made MDA difficult
to achieve such as haemolysis in persons with the genetic defect G6PD
deficiency and limited gastrointestinal tolerance especially when taken on
an empty stomach (
Cappellini and Fiorelli, 2008
). Some trials with precur-
sor drugs to primaquine such as plasmoquine demonstrated the potential
of 8-aminoquinolines but were too toxic for wide-spread use (
Kingsbury
and Amies, 1931
;
Baeza, 1939
;
Barber et al., 1929
,
1932
;
Walker, 1955
;
Field
et al., 1940
). Primaquine was first synthesized in the USA during the Second
WorldWar and subsequently further developed during the KoreanWar when
many soldiers were infected with
P. vivax
with long relapse periods (
Alving
et al., 1952
). The standard dosing regimen of 15 mg daily for 14 days that
was used reflected a compromise between efficacy which was improved at
30 mg daily and toxicity particularly from haemolysis in black soldiers with
G6PD deficiency (
Clayman et al., 1952
;
Hockwald et al., 1952
;
Garrison
et al., 1952
;
Coatney et al., 1953
). Unlike most medications, the efficacy
of primaquine is dependent on the total dose of drug given regardless of
how frequently the medication is given, such that an alternative regimen of
45 mg weekly for 8 weeks was also instituted (
Alving et al., 1960
). Prima-
quine and G6PD deficiency are further discussed in chapter 4, volume 81.
Primaquine has been given to a vast number of people starting with
large groups of US soldiers returning from the Korean War (
Archambeault,
1954
); in G6PD normal individuals, it is well tolerated. Persons with mod-
est enzyme deficiency such as blacks in the USA (usually 5-10% of nor-
mal G6PD activity) only rarely have major haemolytic episodes (
Hockwald
et al., 1952
). Unfortunately, that is not true of severely deficient individu-
als who can experience major haemolytic episodes usually 2-3 days after
starting primaquine that can, on occasion, lead to severe anaemia and acute
