Analysis of MultiplePlasmodium falciparumInfections in Tanzanian Children during the Phase III Trial of the Malaria Vaccine SPf66

Abstract

In the first phase III efficacy trial of the malaria vaccine SPf66 in Africa, MOIs in SPf66- and placebo-vaccinated children were analyzed by polymerase chain reaction-restriction fragment length polymorphism of the Plasmodium falciparum merozoite surface antigen 2 (MSA2). MOIs were significantly reduced in asymptomatic vaccine recipients compared with those in asymptomatic placebo recipients; however, no differences were observed among symptomatic children in the vaccine and control groups. These results show that immunization with SPf66 modulates the course of naturally occurring infections, as reflected by reduced MOIs. In placebo recipients, however, there was a significant negative correlation between numbers of infecting genotypes, as identified by MSA2, and morbidity. Asymptomatic placebo recipients had an average of 5 concurrent infections, whereas children with clinical cases had an average of 3.4 infections. These data provide further evidence that premunition from concurrent infections is important in immunity against clinical malaria. No such effect of multiple infections was found in the vaccinated group.

A prospective study of Plasmodium falciparum multiplicity of infection and morbidity in Tanzanian children

“…A recent study reported an EIR of as low as 29 (95% CI 19-44) bites per annum (Drakeley et al, 2003). As a consequence of the lower transmission rate our study had less power than expected and even the oldest children in our study had experienced much less P. falciparum exposure than those children elsewhere in whom multiple infections appeared to be protective (Al Yaman et al, 1997a;Beck et al, 1997;Contamin et al, 1996;Farnert et al, 1999;Robert et al, 1996). The mean multiplicity in our study was lower than in most of these studies.…”

“…In areas of high endemicity, multiplicity depends on the age of the host (Ntoumi et al, 1995;Smith et al, 1999a) and on the transmission intensity (Arnot, 1998). In Idete, Tanzania, mean MOI in asymptomatic children aged 3-7 years was five infections per carrier (Beck et al, 1997). In contrast, in children aged less than one year in the same village, mean multiplicity was only two infections per child .…”

“…Several studies of partially immune children have found that multiple malaria infections are associated with reduced incidence of clinical episodes of P. falciparum (Al Yaman et al, 1997a;Beck et al, 1997;Farnert et al, 1999). A study in São Tomé found that the apparent protection extended also to nonmalaria fever episodes (Muller et al, 2001).…”

Reduced risk of clinical malaria in children infected with multiple clones of Plasmodium falciparum in a highly endemic area: a prospective community study

“…falciparum. Even in areas of the highest endemicity, the build up of overall clinical immunity takes several years, whilst multiple infections can be ac-quired rapidly even after effective antimalarial treatment (BECK et al, 1997). The immunity associated with coinfecting parasites seems to be an important component of the overall battery of protective responses available to the partially immune host.…”

“…Recent studies have found differences between the parasitological picture in children with asymptomaticP falciparum infections and that in clinical malaria patients from the same highly endemic areas (ENGELBRECHT et al, 1995;CONTAMIN et al, 1996;BECK et al, 1997). Surprisingly, instead of a raised frequency of multiple infections during clinical episodes, these studies have all found the converse.…”