Age-Dependent Distribution of Plasmodium Falciparum Gametocytes Quantified by Pfs25 Real-Time Qt-Nasba in a Cross-Sectional Study in Burkina Faso

Abstract

Sexual stages of Plasmodium falciparum play a key role in the transmission of malaria. Studies on gametocytes are generally based on microscopic detection, but more sensitive detection methods for P. falciparum gametocytes frequently detect sub-patent gametocytes. We used Pfs25 mRNA quantitative-nucleic acid sequence-based amplification (QT-NASBA) to quantify gametocytes in 412 samples from a cross-sectional study in Burkina Faso, covering all age groups, to determine age-related patterns in gametocyte carriage and gametocyte density. The more sensitive QT-NASBA technique gave estimates of gametocyte prevalence 3.3-fold higher than microscopy (70.1% versus 21.4%, respectively). Prevalence of gametocytes significantly decreased with age. Our data suggest that asexual parasite densities are primarily responsible for the age-related decrease of gametocyte prevalence, possibly because of developing asexual stage immunity. Gametocyte densities decrease also with age, primarily because of decreasing asexual parasite densities; only a small but significant age effect on gametocyte density may be caused by developing sexual stage-specific immunity.

Continuing Intense Malaria Transmission in Northern Uganda

“…The relative proportion of parasite carriers that harbored parasites at submicroscopic densities increased with age 34 ; this is likely to be a reflection of acquired immunity that allows adults to control infections more effectively. However, even in the youngest age group a substantial proportion of infections were not detected by microscopy, as was previously shown in areas of intense 35 and low endemicity. 36 Microscopy will be sufficiently sensitive to detect clinically relevant parasite densities, although our data clearly indicate that not every episode of parasitemia with fever equals clinical malaria.…”

Naturally Acquired Immune Responses to Plasmodium falciparum Sexual Stage Antigens Pfs48/45 and Pfs230 in an Area of Seasonal Transmission

“…The close association that we observed between NANP 6 -and Pfs230-specific antibodies may be an indication that the immune responses to sexual stage antigens are therefore also related to recent exposure to infection, explaining the seasonality of the anti-Pfs230 antibody response. Our results showed that many infections with asexual parasites are accompanied by gametocytes (35,37), and this proportion is further increased if submicroscopic gametocyte densities are considered (10). Since asexual parasite carriage increases during the transmission season (36), exposure to gametocytes increases in parallel, possibly explaining the seasonality of anti-sexual stage IgG responses.…”

The Effects of ACT Treatment and TS Prophylaxis on Plasmodium falciparum Gametocytemia in a Cohort of Young Ugandan Children

“…Several papers have noted that increasing age is inversely associated with the risk for gametocyte carriage thought to be caused by the development of immunity to asexual stages, which concomitantly limits the production of gametocytes. [37][38][39] Notably, these other studies used cohorts much older than the cohort described in this paper, typically finding the decline in gametocyte prevalence occurring in individuals older than 10 years. 37 Our findings suggest that children under 4 years may not yet have acquired immunity to asexual or sexual stages; the rise in gametocyte prevalence may, therefore, indicate a rise in the incidence of malaria in this setting.…”

“…[37][38][39] Notably, these other studies used cohorts much older than the cohort described in this paper, typically finding the decline in gametocyte prevalence occurring in individuals older than 10 years. 37 Our findings suggest that children under 4 years may not yet have acquired immunity to asexual or sexual stages; the rise in gametocyte prevalence may, therefore, indicate a rise in the incidence of malaria in this setting. There were several potential limitations to our study.…”