234 
MALARIA 
necessary for protection in hyperendemic 
areas. Each strain must run its course of 
infection and result in a homologous re¬ 
sistance, thus multiplying the interval by 
the number of strains. It has been esti¬ 
mated that a period of 15 years of almost 
constant malarial attacks is necessary be¬ 
fore an individual can be considered 
immune. 
The only indication of a resistance to 
one species being effective against another 
species in man is that reported by James 
and Ciuca (1938). They found that pa¬ 
tients who showed considerable immunity 
to P. vivax were likewise resistant to in¬ 
fections with P. knowlesi, a species of 
monkey malaria. When this species is 
inoculated into persons immune to P. vivax 
a resistance is noted similar to that found 
when a heterologous strain of this parasite 
is inoculated. Primary attacks of P. knowl¬ 
esi are similar to the primary attacks of 
P. vivax, but are less severe in white people. 
In all four species of human malaria 
with the exception of P. falciparum, there 
has been demonstrated a considerable de¬ 
gree of resistance to heterologous strains. 
Following the inoculation of a heterologous 
strain the parasites increase in number and 
may reach the normal level for the strain, 
but in most cases are far below this level. 
Even when the parasite count is at the 
peak the febrile attacks are less intense 
and of short duration. The infection gen¬ 
erally terminates spontaneously with very 
few or no recurrences. 
Immunity in the Different Species 
Only in P. ovale has any critical study 
of the variations in infections with dif¬ 
ferent strains been made. Although Sinton, 
Hutton and Shute (193@b) were able to re¬ 
inoculate some of their patients with strains 
originally obtained from areas separated by 
great distances, some from other continents, 
immunity to the heterologous strains was 
high. Only 18 febrile cases followed re¬ 
inoculation, the average duration in these 
being only 4.5 days. The average length of 
the period of the primary attacks was 18 
days. Only one strain (strain D) showed 
any marked degree of difference from the 
other three. Strain D appeared to be more 
virulent than other strains, the primary 
attack being considerably prolonged in a 
number of cases. When a person who had 
recovered from an infection with another 
strain was reinoculated with this strain of 
parasite, a febrile attack with numerous 
parasites followed. Reciprocal crosses were 
not made as it was not possible to maintain 
all the strains at any one time in the hos¬ 
pital. Other strains showed very little 
heterologous properties. A parallel case 
is found in avian malarial strains that pro¬ 
duce heterologous immune reactions. A 
virulent strain of P. relictum produces a 
low degree of infection in a bird that is 
carrying a latent infection of a very avir- 
ulent strain of the same species. The recip¬ 
rocal cross, however, differs in that the more 
virulent strain confers a complete immun¬ 
ity to inoculation with the avirulent strain. 
Redmond (1939) has indicated that the 
difference in the degree of immunity may 
be largely dependent on the relative num¬ 
ber of parasites occurring during the pri¬ 
mary infections of these two strains. 
Although P. ovale was at one time con¬ 
sidered to be a strain of P. vivax, the 
immune reactions indicate for it a greater 
degree of individuality. Fewer febrile re¬ 
lapses are found following the primary 
attack of P. ovale, but a chronic infection 
may persist for as long as 3 months. In 
both malarious and non-malarious coun¬ 
tries of Europe very little resistance to P. 
ovale has been found by Sinton. 
It has been shown by Ciuca that more 
reinoculations are necessary to produce 
homologous immunity with P. falciparum 
and P. malariae than with P. vivax. In 
subtertian malaria 22 per cent were re¬ 
sistant to reinoculations following the first 
infection but 10 inoculations were required 
to produce immunity in 35 persons of 544 
used in the experiment. Missiroli (1932) 
considers that the immunity developed 
against repeated inoculations of P. vivax 
is more solid than that developed against 
P. falciparum. Boyd, Stratman-Thomas 
and Kitchen (1936a) found good homolo- 
