Extensive genetic diversity of Plasmodium falciparum isolates collected from patients with severe malaria in Dakar, Senegal

Abstract

While some genetic host factors are known to protect against severe Plasmodium falciparum malaria, little is known about parasite virulence factors. We have compared the genetic characteristics of P. falciparum isolates collected from 56 severe malaria patients and from 30 mild malaria patients recruited in Hôpital Principal, Dakar, Senegal. All isolates were typed using polymerase chain reaction amplification of polymorphic genetic loci (MSP-1, MSP-2, HRP1, GLURP, CSP, RESA, and the multigene family Pf60). The complexity of infections was lower in severe than in mild malaria and the parasite genetic diversity in both groups was very large. No specific genetic make-up was associated with severity; there were, however, marked differences in allele frequencies in both groups, with a prevalence up to 60% of MSP-2 alleles specifically observed in the severe malaria isolates. In addition, the presence of MSP-1/RO33 alleles was significantly associated with a higher plasma level of tumour necrosis factor alpha receptor 1 (P < 0.05), a reported indicator of severity in human malaria. These results point to potential differences in the genetic characteristics of parasites inducing severe versus mild pathology.

Polyclonal Plasmodium falciparum malaria in travelers and selection of antifolate mutations after proguanil prophylaxis.

“…The different allelic types of msp-1 and msp-2, as well as the different dhfr mutations, appear to be present in all the different geographic areas visited, but the sample size was too small for a more detailed analysis. However, in contrast to previous findings in endemic areas, 18,19 no association was found between severity of disease and allelic types of msp-1 block2 or msp-2.…”

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.…”

“…Another study at the same site found that asymptomatic 3D7 family infections appeared to protect against subsequent morbidity, but FC27 family infections did not (Al Yaman et al, 1997b). In contrast, a study in Senegal failed to find any association between msp2 type and disease severity (Robert et al, 1996).…”

2. Genotypes of merozoite surface protein 2 of Plasmodium falciparum in Tanzania

“…Potential genotyping markers are sequences showing polymorphism within a parasite population. Polymorphisms in both repetitive sequences and unique sequences have been used for genotyping (ROBERT et al, 1996). When polymorphic repetitive sequences are amplified by PCR, a clone-specific pattern of multiple bands is seen after senaratina the PCR nroducts on a nel.…”