High Plasmodium falciparum longitudinal prevalence is associated with high multiclonality and reduced clinical malaria risk in a seasonal transmission area of Mali.
The effects of persistent Plasmodium falciparum (Pf) infection and multiclonality on subsequent risk of clinical malaria have been reported, but the relationship between these 2 parameters and their relative impacts on the clinical outcome of infection are not understood. A longitudinal cohort study was conducted in a seasonal and high-transmission area of Mali, in which 500 subjects aged 1-65 years were followed for 1 year. Blood samples were collected every 2 weeks, and incident malaria cases were diagnosed and treated. Pf infection in each individual at each time point was assessed by species-specific nested-PCR, and Pf longitudinal prevalence per person (PfLP, proportion of Pf-positive samples over 1 year) was calculated. Multiclonality of Pf infection was measured using a 24-SNP DNA barcoding assay at 4 time-points (two in wet season, and two in dry season) over one year. PfLP was positively correlated with multiclonality at each time point (all r≥0.36; all P≤0.011). When host factors (e.g., age, gender), PfLP, and multiclonality (at the beginning of the transmission season) were analyzed together, only increasing age and high PfLP were associated with reduced clinical malaria occurrence or reduced number of malaria episodes (for both outcomes, P<0.001 for age, and P = 0.005 for PfLP). When age, PfLP and baseline Pf positivity were analyzed together, the effect of high PfLP remained significant even after adjusting for the other two factors (P = 0.001 for malaria occurrence and P<0.001 for number of episodes). In addition to host age and baseline Pf positivity, both of which have been reported as important modifiers of clinical malaria risk, our results demonstrate that persistent parasite carriage, but not baseline multiclonality, is associated with reduced risk of clinical disease in this population. Our study emphasizes the importance of considering repeated parasite exposure in future studies that evaluate clinical malaria risk.
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Yaw
Y
Adomako-Ankomah
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Matthew S
MS
Chenoweth
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Katelyn
K
Durfee
Malaria Research and Training Center, Faculty of Medicine, Pharmacy, and Odontostomatology, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali.
Saibou
S
Doumbia
Malaria Research and Training Center, Faculty of Medicine, Pharmacy, and Odontostomatology, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali.
Drissa
D
Konate
Malaria Research and Training Center, Faculty of Medicine, Pharmacy, and Odontostomatology, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali.
Mory
M
Doumbouya
Malaria Research and Training Center, Faculty of Medicine, Pharmacy, and Odontostomatology, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali.
Abdoul S
AS
Keita
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Daria
D
Nikolaeva
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Gregory S
GS
Tullo
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Jennifer M
JM
Anderson
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Rick M
RM
Fairhurst
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.|Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, United States of America.|Infectious Disease Program, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
Rachel
R
Daniels
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.|Infectious Disease Program, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.|School of Nursing and Health Sciences, Simmons College, Boston, Massachusetts, United States of America.
Sarah K
SK
Volkman
Malaria Research and Training Center, Faculty of Medicine, Pharmacy, and Odontostomatology, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali.
Mahamadou
M
Diakite
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Kazutoyo
http://orcid.org/0000-0003-4455-2432
K
Miura
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Carole A
CA
Long
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology*; D008297:Male; D008302:Mali / Q000453:epidemiology; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D055815:Young Adult