scholarly journals Multi-scale immune selection and the transmission-diversity feedback of Plasmodium falciparum malaria

2017 ◽  
Author(s):  
Thomas Holding ◽  
John Joseph Valletta ◽  
Mario Recker
Keyword(s):  
Plasmodium Falciparum ◽  
Disease Transmission ◽  
Antigenic Variation ◽  
Population Level ◽  
Plasmodium Falciparum Malaria ◽  
Malaria Prevalence ◽  
Feedback Mechanism ◽  
Immune Selection ◽  
Antigenic Diversity ◽  
Transmission Diversity

AbstractAntigenic diversity is a key factor underlying the complex epidemiology of Plasmodium falciparum malaria. Within-host clonal antigenic variation limits host exposure to the parasite’s antigenic repertoire, while the high degree of diversity at the population-level requires multiple exposures for hosts to acquire anti-disease immunity. This diversity is predominantly generated through mitotic and meiotic recombination between individual genes and multi-gene repertoires and is therefore expected to respond dynamically to changes in transmission and immune selection. We hypothesised that this coupling creates a positive feedback mechanism whereby infection and disease transmission promotes the generation of diversity, which itself facilitates immune evasion and hence further infection and transmission. To investigate the link between diversity and malaria prevalence in more detail we developed an individual-based model in which antigenic diversity emerges as a dynamic property from the underlying transmission processes. We show that the balance between stochastic extinction and the generation of new antigenic variants is intrinsically linked to within-host and between-host immune selection, which in turn determines the level of diversity that can be maintained in a given population. We further show that the transmission-diversity feedback can lead to temporal lags in the response to natural or intervention-induced perturbations in transmission rates. These results will add to our understanding of the epidemiological dynamics of P. falciparum malaria in different transmission settings and will have important implications for monitoring and assessing the effectiveness of disease control efforts.

scholarly journals Competition for hosts modulates vast antigenic diversity to generate persistent strain structure in Plasmodium falciparum

2018 ◽  
Author(s):  
Shai Pilosof ◽  
Qixin He ◽  
Kathryn E. Tiedje ◽  
Shazia Ruybal-Pesántez ◽  
Karen P. Day ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Genetic Structure ◽  
Genetic Similarity ◽  
Antigenic Variation ◽  
Host Immunity ◽  
Modular Structure ◽  
Immune Selection ◽  
Frequency Dependent Selection ◽  
Antigenic Diversity ◽  
Human Immune

AbstractIn their competition for hosts, parasites with antigens that are novel to host immunity will be at a competitive advantage. The resulting frequency-dependent selection can structure parasite populations into strains of limited genetic overlap. For Plasmodium falciparum–the causative agent of malaria–in endemic regions, the high recombination rates and associated vast diversity of its highly antigenic and multicopy var genes preclude such clear clustering; this undermines the definition of strains as specific, temporally-persisting gene variant combinations. We use temporal multilayer networks to analyze the genetic similarity of parasites in both simulated data and in an extensively and longitudinally sampled population in Ghana. When viewed over time, populations are structured into modules (i.e., groups) of parasite genomes whose var gene combinations are more similar within, than between, the modules, and whose persistence is much longer than that of the individual genomes that compose them. Comparison to neutral models that retain parasite population dynamics but lack competition reveals that the selection imposed by host immunity promotes the persistence of these modules. The modular structure is in turn associated with a slower acquisition of immunity by individual hosts. Modules thus represent dynamically generated niches in host immune space, which can be interpreted as strains. Negative frequency-dependent selection therefore shapes the organization of the var diversity into parasite genomes, leaving a persistence signature over ecological time scales. Multilayer networks extend the scope of phylodynamics analyses by allowing quantification of temporal genetic structure in organisms that generate variation via recombination or other non-bifurcating processes. A strain structure similar to the one described here should apply to other pathogens with large antigenic spaces that evolve via recombination. For malaria, the temporal modular structure should enable the formulation of tractable epidemiological models that account for parasite antigenic diversity and its influence on intervention outcomes.SignificanceMany pathogens, including the causative agent of malaria Plasmodium falciparum, use antigenic variation, obtained via recombination, as a strategy to evade the human immune system. The vast diversity and multiplicity of genes encoding antigenic variation in high transmission regions challenge the notion of the existence of distinct strains: temporally-persistent and specific combinations of genes relevant to epidemiology. We examine the role of human immune selection in generating such genetic population structure in the major blood-stage antigen of Plasmodium falciparum. We show, using simulated and empirical data, that immune selection generates and maintains ‘modules’ of genomes with higher genetic similarity within, than between, these groups. Selection further promotes the persistence of these modules for much longer times than those of their constituent genomes. Simulations show that the temporal modular structure reduces the speed at which hosts acquire immunity to the parasite. We argue that in P. falciparum modules can be viewed as dynamic strains occupying different niches in human immune space; they are thus relevant to formulating transmission models that encompass the antigenic diversity of the parasite. Our analyses may prove useful to understand the interplay between temporal genetic structure and epidemiology in other pathogens of human and wildlife importance.

scholarly journals Surface alterations of erythrocytes in Plasmodium falciparum malaria. Antigenic variation, antigenic diversity, and the role of the spleen.

1983 ◽  
Vol 157 (4) ◽  
pp. 1137-1148 ◽  
Author(s):  
M Hommel ◽  
P H David ◽  
L D Oligino
Keyword(s):  
Plasmodium Falciparum ◽  
Developmental Stages ◽  
Antigenic Variation ◽  
Plasmodium Falciparum Malaria ◽  
Immune Serum ◽  
Antigenic Determinants ◽  
Original Population ◽  
Antigenic Diversity ◽  
Immune Pressure

The surface of erythrocytes infected with late developmental stages of Plasmodium falciparum is profoundly altered and new antigenic determinants can be detected by surface immunofluorescence using immune squirrel monkey serum. The expression of these parasite-specific antigenic determinants on the surface of the host erythrocyte can be modulated by the presence or absence of the spleen and by immune pressure. An antigenic switch occurred when a cloned population of the Ugandan Palo Alto strain of P. falciparum was transferred from a splenectomized into an intact monkey and this switch was reversible. In another strain (Indochina-1), we showed that the parasites isolated during secondary and recrudescent peaks expressed erythrocyte-associated surface antigens different from the parasites isolated during the primary infection; six variant antigenic types distinct from the original population were isolated in this way. The passive transfer of immune serum can induce antigenic variation and this can occur in a cloned parasite. The various mechanisms of antigenic variation in P. falciparum are discussed in the context of strain-specific diversity and the role of antigenic diversity in acquired immunity.

scholarly journals Relationship between Plasmodium falciparum malaria prevalence, genetic diversity and endemic Burkitt lymphoma in Malawi

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
W. Thomas Johnston ◽  
Nora Mutalima ◽  
David Sun ◽  
Benjamin Emmanuel ◽  
Kishor Bhatia ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Burkitt Lymphoma ◽  
Plasmodium Falciparum Malaria ◽  
Malaria Prevalence

scholarly journals Antigenic Variation in Plasmodium falciparum Malaria Involves a Highly Structured Switching Pattern

2011 ◽  
Vol 7 (3) ◽  
pp. e1001306 ◽  
Author(s):  
Mario Recker ◽  
Caroline O. Buckee ◽  
Andrew Serazin ◽  
Sue Kyes ◽  
Robert Pinches ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Antigenic Variation ◽  
Plasmodium Falciparum Malaria ◽  
Switching Pattern

scholarly journals Estimating the potential impact of Attractive Targeted Sugar Baits (ATSBs) as a new vector control tool for Plasmodium falciparum malaria

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Keith J. Fraser ◽  
Lazaro Mwandigha ◽  
Sekou F. Traore ◽  
Mohamed M. Traore ◽  
Seydou Doumbia ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Vector Control ◽  
Excess Mortality ◽  
Feeding Rate ◽  
Plasmodium Falciparum Malaria ◽  
Malaria Prevalence ◽  
Malaria Burden ◽  
Combining Data ◽  
Potential Impact ◽  
Key Parameter

Abstract Background Attractive targeted sugar baits (ATSBs) are a promising new tool for malaria control as they can target outdoor-feeding mosquito populations, in contrast to current vector control tools which predominantly target indoor-feeding mosquitoes. Methods It was sought to estimate the potential impact of these new tools on Plasmodium falciparum malaria prevalence in African settings by combining data from a recent entomological field trial of ATSBs undertaken in Mali with mathematical models of malaria transmission. The key parameter determining impact on the mosquito population is the excess mortality due to ATSBs, which is estimated from the observed reduction in mosquito catch numbers. A mathematical model capturing the life cycle of P. falciparum malaria in mosquitoes and humans and incorporating the excess mortality was used to estimate the potential epidemiological effect of ATSBs. Results The entomological study showed a significant reduction of ~ 57% (95% CI 33–72%) in mosquito catch numbers, and a larger reduction of ~ 89% (95% CI 75–100%) in the entomological inoculation rate due to the fact that, in the presence of ATSBs, most mosquitoes do not live long enough to transmit malaria. The excess mortality due to ATSBs was estimated to be lower (mean 0.09 per mosquito per day, seasonal range 0.07–0.11 per day) than the bait feeding rate obtained from one-day staining tests (mean 0.34 per mosquito per day, seasonal range 0.28–0.38 per day). Conclusions From epidemiological modelling, it was predicted that ATSBs could result in large reductions (> 30% annually) in prevalence and clinical incidence of malaria, even in regions with an existing high malaria burden. These results suggest that this new tool could provide a promising addition to existing vector control tools and result in significant reductions in malaria burden across a range of malaria-endemic settings.

scholarly journals Gametocyte Carriages of Plasmodium falciparum (pfs25) and Plasmodium vivax (pvs25) during Mass Screening and Treatment in West Timor, Indonesia a Longitudinal Prospective Study

2020 ◽  
Author(s):  
Ayleen Alicia Kosasih ◽  
Cristian Koepfli ◽  
M. Sopiyudin Dahlan ◽  
William A. Hawley ◽  
J. Kevin Baird ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Mass Screening ◽  
Population Level ◽  
Malaria Prevalence ◽  
Blood Samples ◽  
Gametocyte Carriage ◽  
Significance Threshold ◽  
Significant Difference ◽  
West Timor ◽  
Pcr Diagnostics

Abstract Background: Three rounds of mass screening and treatment (MST) demonstrated no effect on Plasmodium falciparum and P. vivax incidence in West Timor, Indonesia. This study nested within that trial evaluated the effect of MST on gametocyte carriage.Methods: Microscopy and PCR diagnostics were applied to study subjects through 3 months of MST involving dihydroartemisinin-piperaquine (DHP) and primaquine based on infecting Plasmodium species. RT-qPCR targeting the pfs25 and pvs25 sequences was conducted to detect and quantify gametocytes in blood samples of P. falciparum and P. vivax- infected subjects. Data from the baseline and endpoint were compared (p<=0.05 as the significance threshold).Results:Between baseline and endpoint, prevalence remained unchanged for P. falciparum (6%=52/811 versus 7%=50/740, p=0.838) and decreased slightly for P. vivax (24%=192/811 versus 19%=142/740, p=0.035). No significant difference was observed in gametocyte carriage rates for either P. falciparum (43%=19/44 versus 59%=23/39, OR & 95%CI=1.89, 0.72-4.97) or P. vivax (39%=49/125 versus 37%=39/106, OR & 95%CI=0.90, 0.51-1.59). Despite the insignificant differences between the two time points, the majority of positive subjects at the endpoint were newly parasitemic individuals (new infections) (Pf:92%=46/50, Pv: 65%=93/142). This result was similarly demonstrated for the transmissible stage - where new gametocyte carriers dominated endpoint positive subjects (Pf: 96%=22/23, Pv: 95%=37/39). Conclusion:Although three rounds of MST decreased individual parasitemia and gametocytemia based on diagnosis and treatment, this failed to impact malaria prevalence at a population level due to the development of new infected individuals that can sustain transmission. These observations in part explains why MST failed to impact transmission of malaria in this transmission context.

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