Relapse - Advances in Parasitology - page 123

in malaria therapy, the 'strains' became purified through successive inter-
breeding to a very closely related group of genotypes. In contrast, multiple
unrelated genotype infections are common in natural infections.
4.3. Effects of Drugs on Relapse Intervals
Since the introduction of mepacrine (atebrine, quinacrine) in 1932, a drug
which has a terminal elimination half-life of over 1 month, it was observed
that early relapses were delayed by approximately 30 days compared with
quinine (half-life in malaria 16 hours) treatment (i.e. from 3-7 weeks)
( Most, 1963 ; Noe et al., 1946 ; Bianco et al., 1947 ; Whorton et al., 1947 ;
Craige et al., 1947 ). Later, chloroquine, which is also very slowly elim-
inated, was found to delay early relapse appearance by 2-6 weeks ( Jef-
fery, 1956 ). Larger doses of the anti-malarials resulted in longer intervals
to relapse consistent with a concentration-dependent slowing of asexual
growth rates. Slowly eliminated anti-malarials delayed the onset of P. vivax
relapse, and consequently, reduced their frequency, but they did not appear
to reduce the overall number of relapses experienced ( Most, 1963 ). Only the
8-aminoquinolines reduced or prevented relapses. The relapse-preventing
properties of these drugs, and their synergistic action with quinine, were
demonstrated within years of their introduction in the mid-1920s ( Sinton
and Bird, 1928 ; Sinton et al., 1930 ; James, 1931b ).
4.4. The Proportion of P. vivax Infections which Relapse
This is often considered an intrinsic property of the malaria parasites,
which varies considerably by geographic region. Tropical 'strains' relapsed
more than temperate 'strains'. But the relapse proportion is also clearly a
function of the sporozoite inoculum and immunity (if any). In the Sec-
ond World War, relapse rates were very high in soldiers who were gener-
ally non-immune and presumably experienced intense exposure. Overall,
reported relapse rates have varied from 0 to 100%! ( White, 2011 ). In many
cases, relapse rates are likely to have been underestimated as follow-up peri-
ods, particularly in recent studies, were often 3 months or less, and in the
majority of studies, radical treatments were being evaluated. In addition,
studies conducted in endemic areas cannot reliably exclude reinfection.
Without radical treatment, the proportion of patients who experience one
relapse, the proportion of these patients who have a second relapse, and the
proportion of these who have a third and so on, is constant ( White, 2011 ;
Höring, 1947 ; Eyles and Young, 1948 ; Most, 1963 ; Bianco et al., 1947 ; Hill
and Amatuzio, 1949 ; Boyd and Kitchen, 1943 ; Mowrey, 1963 ). Thus if x is