Dataset Information

Co-transmission of Related Malaria Parasite Lineages Shapes Within-Host Parasite Diversity.

ABSTRACT: In high-transmission regions, we expect parasite lineages within complex malaria infections to be unrelated due to parasite inoculations from different mosquitoes. This project was designed to test this prediction. We generated 485 single-cell genome sequences from fifteen P. falciparum malaria patients from Chikhwawa, Malawi-an area of intense transmission. Patients harbored up to seventeen unique parasite lineages. Surprisingly, parasite lineages within infections tend to be closely related, suggesting that superinfection by repeated mosquito bites is rarer than co-transmission of parasites from a single mosquito. Both closely and distantly related parasites comprise an infection, suggesting sequential transmission of complex infections between multiple hosts. We identified tetrads and reconstructed parental haplotypes, which revealed the inbred ancestry of infections and non-Mendelian inheritance. Our analysis suggests strong barriers to secondary infection and outbreeding amongst malaria parasites from a high transmission setting, providing unexpected insights into the biology and transmission of malaria.

SUBMITTER: Nkhoma SC

PROVIDER: S-EPMC7159252 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Co-transmission of Related Malaria Parasite Lineages Shapes Within-Host Parasite Diversity.

Nkhoma Standwell C SC Trevino Simon G SG Gorena Karla M KM Nair Shalini S Khoswe Stanley S Jett Catherine C Garcia Roy R Daniel Benjamin B Dia Aliou A Terlouw Dianne J DJ Ward Stephen A SA Anderson Timothy J C TJC Cheeseman Ian H IH

Cell host & microbe 20191231 1

In high-transmission regions, we expect parasite lineages within complex malaria infections to be unrelated due to parasite inoculations from different mosquitoes. This project was designed to test this prediction. We generated 485 single-cell genome sequences from fifteen P. falciparum malaria patients from Chikhwawa, Malawi-an area of intense transmission. Patients harbored up to seventeen unique parasite lineages. Surprisingly, parasite lineages within infections tend to be closely related, s ...[more]

PMID: 31901523

Similar Datasets

Project description:Plasmodium falciparum, the most virulent human malaria parasite, undergoes asexual reproduction within the human host, but reproduces sexually within its vector host, the Anopheles mosquito. Consequently, the mosquito stage of the parasite life cycle provides an opportunity to create genetically novel parasites in multiply-infected mosquitoes, potentially increasing parasite population diversity. Despite the important implications for disease transmission and malaria control, a quantitative mapping of how parasite diversity entering a mosquito relates to diversity of the parasite exiting, has not been undertaken. To examine the role that vector biology plays in modulating parasite diversity, we develop a two-part model framework that estimates the diversity as a consequence of different bottlenecks and expansion events occurring during the vector-stage of the parasite life cycle. For the underlying framework, we develop the first stochastic model of within-vector P. falciparum parasite dynamics and go on to simulate the dynamics of two parasite subpopulations, emulating multiply infected mosquitoes. We show that incorporating stochasticity is essential to capture the extensive variation in parasite dynamics, particularly in the presence of multiple parasites. In particular, unlike deterministic models, which always predict the most fit parasites to produce the most sporozoites, we find that occasionally only parasites with lower fitness survive to the sporozoite stage. This has important implications for onward transmission. The second part of our framework includes a model of sequence diversity generation resulting from recombination and reassortment between parasites within a mosquito. Our two-part model framework shows that bottlenecks entering the oocyst stage decrease parasite diversity from what is present in the initial gametocyte population in a mosquito's blood meal. However, diversity increases with the possibility for recombination and proliferation in the formation of sporozoites. Furthermore, when we begin with two parasite subpopulations in the initial gametocyte population, the probability of transmitting more than two unique parasites from mosquito to human is over 50% for a wide range of initial gametocyte densities.

Project description:Interactions among parasite species coinfecting the same host individual can have far reaching consequences for parasite ecology and evolution. How these within-host interactions affect epidemics may depend on two non-exclusive mechanisms: parasite growth and reproduction within hosts, and parasite transmission between hosts. Yet, how these two mechanisms operate under coinfection, and how sensitive they are to the composition of the coinfecting parasite community, remains poorly understood. Here, we test the hypothesis that the relationship between within- and between-host transmission of the fungal pathogen, Phomopsis subordinaria, is affected by co-occurring parasites infecting the host plant, Plantago lanceolata. We conducted a field experiment manipulating the parasite community of transmission source plants, then tracked P. subordinaria within-host transmission, as well as between-host transmission to naïve recipient plants. We find that coinfection with the powdery mildew pathogen, Podosphaera plantaginis, causes increased between-host transmission of P. subordinaria by affecting the number of infected flower stalks in the source plants, resulting from altered auto-infection. In contrast, coinfection with viruses did not have an effect on either within- or between-host transmission. We then analyzed data on the occurrence of P. subordinaria in 2018 and the powdery mildew in a multi-year survey data set from natural host populations to test whether the positive association predicted by our experimental results is evident in field epidemiological data. Consistent with our experimental findings, we observed a positive association in the occurrence of P. subordinaria and historical powdery mildew persistence. Jointly, our experimental and epidemiological results suggest that within- and between-host transmission of P. subordinaria depends on the identity of coinfecting parasites, with potentially far-reaching effects on disease dynamics and parasite co-occurrence patterns in wild populations.Supplementary informationThe online version contains supplementary material available at 10.1007/s10682-022-10182-9.

Project description:Plasmodium infections trigger complex immune reactions from their hosts against several life stages of the parasite, including gametocytes. These immune responses are highly variable, depending on age, genetics, and exposure history of the host as well as species and strain of parasite. Although the effects of host antibodies that act against gamete stages in the mosquito (due to uptake in the blood meal) are well documented, the effects of host immunity upon within-host gametocytes are not as well understood. This report consists of a theoretical population biology-based analysis to determine constraints that host immunity impose upon gametocyte population growth. The details of the mathematical models used for the analysis were guided by published reports of clinical and animal studies, incorporated plausible modalities of immune reactions to parasites, and were tailored to the life cycl es of the two most widespread human malaria pathogens, Plasmodium falciparum and Plasmodium vivax.For the same ability to bind and clear a target, the model simulations suggest that an antibody attacking immature gametocytes would tend to lower the overall density of transmissible mature gametocytes more than an antibody attacking the mature forms directly. Transmission of P. falciparum would be especially vulnerable to complete blocking by antibodies to its immature forms since its gametocytes take much longer to reach maturity than those of P. vivax. On the other hand, antibodies attacking the mature gametocytes directly would reduce the time the mature forms can linger in the host. Simulation results also suggest that varying the standard deviation in the time necessary for individual asexual parasites to develop and produce schizonts can affect the efficiency of production of transmissible gametocytes.If mature gametocyte density determines the probability of transmission, both Plasmodium species, but especially P. falciparum, could bolster this probability through evasion or suppression of host immune responses against the immature gametocytes. However, if the long term lingering of mature gametocytes at low density in the host is also important to ensure transmission, then evasion or suppression of antibodies against the mature stages would bolster probability of transmission as well.

Project description:Malaria-infected individuals often harbor mixtures of genetically distinct parasite genotypes. We studied intra-host dynamics of parasite genotypes co-infecting asymptomatic adults in an area of intense malaria transmission in Chikhwawa, Malawi. Serial blood samples (5 ml) were collected over seven consecutive days from 25 adults with asymptomatic Plasmodium falciparum malaria and analyzed to determine whether a single peripheral blood sample accurately captures within-host parasite diversity. Blood samples from three of the participants were also analyzed by limiting dilution cloning and SNP genotyping of the parasite clones isolated to examine both the number and relatedness of co-infecting parasite haplotypes. We observed rapid turnover of co-infecting parasite genotypes in 88% of the individuals sampled (n = 22) such that the genetic composition of parasites infecting these individuals changed dramatically over the course of seven days of follow up. Nineteen of the 25 individuals sampled (76%) carried multiple parasite genotypes at baseline. Analysis of serial blood samples from three of the individuals revealed that they harbored 6, 12 and 17 distinct parasite haplotypes respectively. Approximately 70% of parasite haplotypes recovered from the three extensively sampled individuals were unrelated (proportion of shared alleles <83.3%) and were deemed to have primarily arisen from superinfection (inoculation of unrelated parasite haplotypes through multiple mosquito bites). The rest were related at the half-sib level or greater and were deemed to have been inoculated into individual human hosts via parasite co-transmission from single mosquito bites. These findings add further to the growing weight of evidence indicating that a single blood sample poorly captures within-host parasite diversity and underscore the importance of repeated blood sampling to accurately capture within-host parasite ecology. Our data also demonstrate a more pronounced role for parasite co-transmission in generating within-host parasite diversity in high transmission settings than previously assumed. Taken together, these findings have important implications for understanding the evolution of drug resistance, malaria transmission, parasite virulence, allocation of gametocyte sex ratios and acquisition of malaria immunity.

Dataset Information

Co-transmission of Related Malaria Parasite Lineages Shapes Within-Host Parasite Diversity.

Publications

Co-transmission of Related Malaria Parasite Lineages Shapes Within-Host Parasite Diversity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets