Meiosis simulations.

<p>Blue indicates data obtained from the progeny of strains crossed in the laboratory. Orange indicates simulated data using the non-obligate chiasma meiosis model while green indicates simulated data from the obligate chiasma meiosis model. <b>A</b>) Barplots of the intercrossover distances of all 14 chromosomes of the <i>P</i>. <i>falciparum</i> genome. <b>B</b>) Barplots of the number of chiasma scattered throughout the genome. For <b>A</b> and <b>B</b>, simulated data were generated using a shape parameter of 2. <b>C</b>) Line plots of the negative pseudo-likelihood values of the non-obligate and obligate meiosis models at different levels of crossover interference. Along the x-axis are different levels of crossover interference (determined by the value of the shape parameter). A shape parameter of 1 indicates no crossover intereference. Lower negative pseudo-likelihood values indicate a better fit to the data obtained from the progeny of experimentally lab-crossed strains.</p

Model of parasite transmission.

<p>Model of transmission where genetically distinct parasites are distinguished by color. Parameter values are drawn from the set {1, 2, 3, 4, 5, 10, 20}, which represents the range of values observed in real life simulations. The bold number indicates the value in the example shown in the figure. Gametocytes are sampled from an initial polygenomic infection comprised of unrelated parasite strains. Sampled gametocytes are used to create oocysts within the mosquito midgut (middle). Each oocyst summarizes the entire sequence of events starting from gamete fusion to the end of meiosis. Oocysts are represented using a stylized pedigrees tree, where the crescents at the top represent parental strains undergoing meiosis, the oval in the center indicates whether the mating event is the result of selfing (solid color) or outcrossing (color-gradient), and the sporozoites at the bottom represent the four meiotic products generated through meiosis. Those with multiple colors indicate that genomes have undergone effective recombination and are genetically distinct from the parental strains and to each other. Sporozoites are sampled from the total pool of meiotic products to determine the genetic composition of the subsequent host infection. The number of sporozoites sampled is determined by the infected hepatocyte count used in the simulation.</p

Relatedness of polygenomic infections after multiple transmission events.

<p>Line plots of the average relatedness of polygenomic infections <b>(A,C)</b> and proportion of simulations that have converged to the transmission of a single strain after multiple transmission events across 500 simulations <b>(B,D)</b>. Only results from simulations where gametocyte-sampling probabilities are equal <b>(A,B)</b> and where gametocyte sampling probabilities are skewed by a 10:1 ratio between the most frequent and least frequent strain <b>(C,D</b>) are shown. Blue = No superinfection. Green = Superinfection where the resident strain is the same as one of the parental strains in the initial infection. Red = Superinfection where the resident strain is unrelated to the parental strains in the initial infection. Purple = Superinfection where the resident strain is unrelated and different in each transmission event. Solid dark lines indicate results where the initial polygenomic infection had a COI = 2 and light dotted lines indicate results where the initial polygenomic infection had a COI = 5.</p

Pedigree and kinship frequencies from multiple oocyst simulations.

<p>Stacked line charts of the frequencies of different pedigrees (A-D) and kinships (a-d) plotted against oocyst count. Each subplot represents a scenario with a different COI (A/a = 2, B/b = 3, C/c = 4, D/d = 20). Only the results from simulations where infected hepatocyte count = 10 are shown. Genetic clones are defined as those emerging from oocysts characterized by pedigree 1 and 3; genetically identical meiotic siblings are still classified as meiotic siblings in this graph.</p

Relatedness of cotransmitted strains when oocyst count is 1.

<p>Violin plots of the relatedness of cotransmitted strains in single oocyst simulations. Only the results for simulations with infected hepatocyte count of 2 (<b>A</b>) or 5 (<b>B</b>) are shown. The expected relatedness (in terms of both median and mean) is always 0.33. A box plot is drawn in the center of each violin plot, where the white dot represents the median of the distribution, the thicker line represent the interquartile range, and the thinner line represents the whiskers of the box plot, up to 1.5 times the interquartile range. The horizontal dotted line represents the value of 0.33.</p

Relatedness of cotransmitted strains in multiple oocyst simulations.

<p>Violin plots of the relatedness of cotransmitted strains in multiple oocyst simulations. Only the results for simulations with oocyst counts of 2 (A) and 20 (B) and infected hepatocyte counts of 2 are shown. The expected relatedness of cotransmitted strains declines with increasing COI. A box plot is drawn in the center of each violin plot, where the white dot represents the median of the distribution, the thicker line represent the interquartile range, and the thinner line represents the whiskers of the box plot, up to 1.5 times the interquartile range. The horizontal dotted line represents the value of 0.33.</p

Pedigrees between parasites and their expected relatedness.

<p>The 9 possible pedigrees describing parasite pairs. Pedigrees represent the genetic ancestry of parasites and the oocysts they are sampled from. Circles at the top of each pedigree represent the gametes that fuse and undergo meiosis while circles at the bottom represent the sporozoites that are generated following meiosis and expansion in the oocyst. Different colors represent different genomes. Sporozoites with mixed colors indicate they are the result of outcrossing. Blue arrows between pedigrees indicate that sporozoites are sampled from different oocysts. Parasites can be sampled from the same oocyst (pedigrees 1 and 2) or from multiple oocysts (pedigrees 3–9). For pedigree 2, the distribution of expected relatedness was bimodal, and we provide the average across the entire distribution (top) as well as the two modes (bottom). Pedigree 6 and 8 are only accessible when COI ≥ 3 and pedigree 9 is only accessible when COI ≥ 4.</p

Infection detection strategies differ in ability to minimize overtreatment.

<p>(A) Success of infection detection strategies at finding infected individuals while avoiding overtreatment of uninfected individuals. Results shown are means of 100 stochastic realizations per coverage level. Ticks indicate 20% steps in coverage. (B) Success of infection detection strategies at averting clinical cases while minimizing overtreatment at 80% coverage. Results shown are means and 95% confidence intervals of 100 stochastic realizations per coverage level. HFCA populations were normalized to 1000.</p

MDA and sensitive serological diagnostics are the most effective detection strategies for malaria elimination.

<p>(A) Probability that less than one new infection is seeded from vectors infected in the 30 days post-campaign. Results shown are means of 1000 stochastic realizations per coverage level. (B) Success of infection detection strategies at finding infected individuals while minimizing overtreatment. Results shown are means of 1000 stochastic realizations per coverage level. Ticks indicate 20% steps in coverage.</p

Infection detection strategies differ in ability to reduce transmission.

<p>(A) Success of infection detection strategies at depleting the infectious reservoir. Fraction of infectious reservoir eliminated was defined as the decrease in infectious potential integrated over 30 days post-campaign. Results shown are means of 100 stochastic realizations per coverage level. (B) Success of infection detection strategies at averting new infections. Results shown are means of 100 stochastic realizations per coverage level. HFCA populations were normalized to 1000.</p