Plasmodium falciparum: Extensive Polymorphism in Merozoite Surface Antigen 2 Alleles in an Area with Endemic Malaria in Papua New Guinea

Felger, Ingrid; Tavul, Livingstone; Kabintik, S.; Marshall, Vikki M.; Genton, Blaise; Alpers, Michael P.; Beck, Hans‐Peter

doi:10.1006/expr.1994.1070

Cited by 122 publications

(105 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, the increase in the proportion of FC27 family infections with age and the higher parasite densities associated with this family confirm the previous findings from both Papua New Guinea (Felger et al, 1994) and Tanzania , which suggested that the alleles of the FC27 family were more successful in evading the host's immune response. In support of this, both a case control study, and a vaccine field trial in Papua New Guinea found that FC27-type alleles were strongly associated with malaria morbidity (Engelbrecht et al, 1995;Genton et al, 2002).…”

Section: Discussionsupporting

confidence: 87%

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

Henning

Schellenberg

Smith

et al. 2004

Transactions of the Royal Society of Tropical Medicine and Hygi

Self Cite

View full text Add to dashboard Cite

Summary Several studies suggest that in individuals with substantial previous exposure to malaria, co-infection with multiple clones of Plasmodium falciparum can protect against subsequent clinical malaria attacks. Other studies, mainly of individuals with little previous exposure, found the converse relationship. To test whether acquisition of such cross-protection tracks the acquisition of clinical immunity in general, 610 Tanzanian children aged 0-6 years were enrolled in a nine-month prospective study of the risk of morbidity in relation to parasitological status and merozoite surface protein 2 genotypes on enrolment. Prevalence of parasitaemia and multiplicity of infection increased with age. In the first year of life, the incidence of clinical malaria was almost three times higher in children with parasites at baseline than in those without. In older children, baseline P. falciparum infections appeared to protect against both parasitaemic and non-parasitaemic fever episodes. In children aged less than three years, baseline multiple infection tended to be associated with higher prospective risk of clinical malaria than single infection while in children aged more than three years the converse was found, but these effects were not statistically significant. These results provide further evidence that relationships between asymptomatic malaria infections and clinical malaria change with cumulative exposure.

show abstract

Section: Discussionsupporting

confidence: 87%

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

Henning

Schellenberg

Smith

et al. 2004

Transactions of the Royal Society of Tropical Medicine and Hygi

Self Cite

View full text Add to dashboard Cite

show abstract

“…This allows further differentiation between 3D7-type alleles producing a Hinfl fragment of similar size (differences x10 bp). The conserved and variable restriction fragments resulting from RsaI, DdeI and ScrFI digests of 3D7-type alleles have been described earlier (FELGER et al, 1994). These additional restriction digests are generally done if infections from different blood samples need to be compared to each other.…”

Section: Multiple Infections In Tanzanian Blood Samplesmentioning

confidence: 99%

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

Felger

Irion

Steiger

et al. 1999

Transactions of the Royal Society of Tropical Medicine and Hygi

Self Cite

View full text Add to dashboard Cite

The merozoite surface protein 2 (MSP2) of Plasmodium falciparum is extremely polymorphic: 82 different msp2 alleles were found in 4 studies of molecular epidemiology conducted in Tanzania. This diversity renders msp2 suitable as a marker gene for the genotyping of I? falciparum infections. Amplification of msp2 by the polymerase chain reaction (PCR), and subsequent restriction digests of the PCR product @'CR-restriction fragment length polymorphism genotyping), has proved to be an informative tool for enumerating multiple concurrent infections in a blood sample, and distinguishing individual alleles. Depending on the specific questions asked in a genotyping study, analytical techniques of different degrees of complexity are employed. The restriction fragments resulting from a single Hinff digest generally allow the enumeration of multiple concurrent infections and the determination of their allelic families.When a restriction pattern is too complex to be resolved, owing to the high number of concurrent infections, or due to the appearance of previously undescribed alleles, one or more additional digests (DdeI, RsaI, S&I) may be necessary. To determine individual alleles unequivocally, in particular in longitudinal studies, when several consecutive samples need to be compared with each other, a more detailed analysis involving all 3 additional digests is applied. The methodological experience and results gained in 4 epidemiological field studies involving msp2 genotyping are summarized. We also provide the HinfI restriction patterns and some nucleotide sequences of the alleles found so far in our studies inTanzania.

show abstract

“…High polymorphism has been shown in merozoite surface protein 1(msp1), merozoite surface protein 2 (msp2) and glutamate rich protein (glurp) genes of P. falciparum in different geographical locations in malaria endemic areas (Felger et al 1994;Babiker & Walliker 1997 1 ; Snounou et al 1999;Magesa et al 2001;PeyerlHoffmann et al 2001;Aubouy et al 2003). Therefore, these loci have been used in many trials to distinguish recrudescence from new infections.…”

Section: Introductionmentioning

confidence: 99%

Molecular genotyping to distinguish between recrudescents and new infections in treatment trials of Plasmodium falciparum malaria conducted in Sub‐Saharan Africa: adjustment of parasitological outcomes and assessment of genotyping effectiveness

Mugittu

Adjuik

Snounou

et al. 2006

Tropical Med Int Health

View full text Add to dashboard Cite

SummaryMolecular genotyping of baseline and post-treatment recurrent Plasmodium falciparum is recommended to distinguish recrudescent from new infections. However, genotyping performance and adjustment of treatment outcomes have not been evaluated in large field trials. Parasitological outcomes were assessed in nine double-blinded trials of uncomplicated P. falciparum malaria in African children treated with artesunate/placebo plus standard monotherapies. Day 28 failure rates were adjusted by stepwise genotyping the P. falciparum glutamate rich protein (glurp), merozoite surface protein 1 (msp1) and 2 (msp2). We calculated overall and laboratory genotyping performance and compared unadjusted (crude) and PCR-adjusted outcomes. 3455 (93.6%) of 3691 enrolled patients were evaluable by Day 28. 767 (22%) had post-Day 14 recurrent parasitemias of which 686 could be genotyped: 246 were recrudescences, 286 new infections and 154 unresolved. The overall and laboratory genotyping performance were 69 (12-100)% and 78 (50-100)%, respectively. The mean Day 28 crude parasitological failure rate was 44 (range 3-87)%. PCR-adjusted rates were 36 (range 2-86)% if unresolved infections were counted as failures or 33 (range 2-86)% if excluded from analysis. The overall difference between crude Day 28 and Day 14 failure rates was 22% (95% CI 20.3, 24.6) but decreased to 14% (95% CI 12.1, 16.3) if unresolved infections are counted as failures, or to 11% (95% CI 9.8, 16.3) if unresolved infections are excluded from the analysis. Genotyping refined treatment outcomes but diligence is needed in sample collection and analysis to improve its performance. Our findings support the WHO recommendation of PCR genotyping in malaria clinical trials and suggest that stepwise genotyping of only two loci (msp2 and msp1 or glurp) can reliably discriminate recrudescences from new infections.

show abstract

Plasmodium falciparum: Extensive Polymorphism in Merozoite Surface Antigen 2 Alleles in an Area with Endemic Malaria in Papua New Guinea

Cited by 122 publications

References 0 publications

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

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

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

Molecular genotyping to distinguish between recrudescents and new infections in treatment trials of Plasmodium falciparum malaria conducted in Sub‐Saharan Africa: adjustment of parasitological outcomes and assessment of genotyping effectiveness

Contact Info

Product

Resources

About