Experimental infection and protection against ... - TI Pharma

Protection against a Malaria Challenge by Sporozoite Inoculation 181
No parasites were seen in the thick blood-smears of any of the 10 vera following
each of the three immunization sessions under CQ prophylaxis, but after the first
immunization a brief sub-microscopic parasitemic episode was detected in all
vera (Figure 2a). This was not unexpected, since CQ has no effect against either
sporozoites, liver-stage parasites, or the early ring forms of the first generation
of blood-stage parasites caused by merozoites released from mature hepatic
schizonts [11]. Following each of the subsequent two immunizations, a
progressively reduced incidence and burden of sub-microscopic parasitemia was
seen.
In line with these findings, all vera reported solicited or unsolicited adverse
events at least once during the immunization phase. When excluding local
itching after the mosquito bites, adverse events were most commonly reported
after the first immunization (9/10 volunteers), with headache being the most
frequent (7/10) (Table 1). Only few adverse events occurred subsequently (0/10
and 2/10 volunteers after the second and third immunization respectively).
Severe adverse events were reported by three vera: two experienced fever
above 39°C after the first immunization, one reported severe malaise after the
last immunization.
Following challenge with homologous NF54 strain of P. falciparum, asexual
blood-stage parasites were detected in thick blood smears of all 5 control
volunteers between days 7 and 10.6 post-exposure (mean pre-patent period 9.2
days). Real-time PCR analyses revealed the expected cyclical multiplication of
blood-stage parasites (Figure 2b). Clinical course and kinetics of parasite
multiplication were identical to those in previous studies involving naïve
volunteers [23,24], with all controls reporting severe events, in particular fever
above 39°C and malaise (Table 1). In marked contrast, there was no evidence of
blood-stage parasites in any of the vera at any time during the post-challenge
follow-up period till day 20, either by repeated microscopy of thick blood smears
or by real-time PCR analyses (Figure 2b). Interestingly, 9/10 vera did report mild
to moderate events in the week following challenge. No serious adverse events
occurred during any part of the trial and all 15 volunteers completed follow-up
according to protocol.
Mean peak chloroquine and desbutyl-chloroquine levels measured 24 hours
after administration were 76 µg/l (range 58-104 µg/l) and 13 µg/l (5-33 µg/l)
respectively and did not differ between control and vera. The day before
challenge plasma levels had dropped to 8 µg/l (range