Fig 1.
Conceptual model representing the impact of fipronil-induced adult and larval mortality on population dynamics of sand flies.
Sand flies are represented as eggs, larvae, pupae, pre-reproductive adults, pre-oviposition adults, reproductive adults, and post reproductive adults. Pre-reproductive adults require a blood meal to proceed with oviposition. Fipronil increases the mortality rate of adults feeding on treated cattle and larvae feeding on feces excreted by treated cattle. All processes represented by eqs 1–3 and 5–13 are temperature dependent.
Fig 2.
Curves representing of the daily contribution of temperature toward development of sand fly stages.
(A) eggs (Eq 1), (B) larvae (Eq 2), (C) pupae (Eq 3), and (D) pre-oviposition adults (Eq 5). Red squares represent the data points used to generate the curves.
Fig 3.
Curves representing (A) the daily probability of obtaining a blood meal as a function of days-post-emergence (Eq 4) and (B) the number of eggs laid per reproductive female as a function of current air temperature (Eqs 6 and 7).
Red squares represent the data points used to generate the curves.
Fig 4.
Curves representing the temperature-dependent natural mortality of sand fly stages.
(A) eggs (Eq 8), (B) larvae (Eqs 9 and 10), (C) pupae (Eq 11), and (D) adults (Eqs 12 and 13). Egg and pupal mortality are polynomial functional relationships whereas larval and adult mortality increases exponentially from the optimum temperatures for survivorship towards the upper and lower thermal limits. Red squares represent the data points used to generate the curves.
Fig 5.
Curve(s) representing fipronil-induced sand fly mortality.
(A) the decline in fipronil efficacy (measured as daily probability of mortality of adults) in cattle blood as a function of days post-application (Eq 15) and (B) the decline in fipronil efficacy (measured as daily proportional mortality of larvae) in cattle feces as a function of number of days post-defecation (Eq 16) (colored lines) and the number of days-post-application when defecation occurred (Eq 17) (black line).
Table 1.
Experimental design involving 20 treatment schemes reapplied over a three-year period (with 10 replicate stochastic (Monte Carlo) simulations per scheme).
Fig 6.
(A) Comparison of simulated and observed mean development times of sand fly eggs, larvae, and pupae at the indicated temperatures, and (B) simulated development times of eggs, larvae, and pupae at the indicated temperatures encompassing the range of soil temperatures collected during a field study in West Bengal, India [49] to which we assumed immature sand flies were exposed.
Vertical bars in (A) represent ±1 standard deviation of development times at 20°C [16,18] and the range of development times at temperatures 25.5–30.5°C.
Fig 7.
Comparison of (A) simulated and observed daily proportion of blood meals obtained [44] by pre-reproductive females as a function of days-post-emergence, (B) simulated and observed [19] mean lengths of the pre-oviposition period at the indicated temperatures, and (C) simulated and observed [19] number of (female) eggs laid per female at the indicated temperatures.
Vertical bars represent ±1 standard deviation. The number of eggs observed in the laboratory in part c is divided by two to represent only females.
Fig 8.
Comparison of (A) simulated and observed [16] natural mortality rates of eggs, larvae, and pupae at the indicated temperatures (range reported), and (B) simulated and observed [16,45] mean longevities of adult sand flies at the indicated temperatures.
Vertical bars represent the range of values.
Fig 9.
Comparison of (A) simulated and observed [25] probabilities of fipronil-induced mortality of adults obtaining a blood meal the indicated number of days post-treatment, and (B) simulated and observed [25] fipronil-induced mortality rates of larvae exposed to organic matter containing cattle feces deposited the indicated number of days post-treatment.
Fig 10.
The daily minimum air temperature data recorded at a village in Bihar, India (unpublished data from daily collections used to develop Table 1 in [21]) and a cosine curve fitted to a graphical representation of annual fluctuations in soil temperatures in West Bengal, India [49], which were used to calibrate the time series of air temperatures and temperatures within organic matter, respectively, used in the simulation model.
Fig 11.
Fluctuations in abundance of adult sand flies observed during year 3 of the baseline simulation.
Red brackets indicate a generation of overwintering sand flies. Black brackets indicate the time between initial oviposition and the first post-winter peak in abundance of adults (P1). PL indicates the largest peak abundance of adults.
Fig 12.
Fluctuations in abundances of (A) eggs, (B) larvae, (C) pupae, and (D) adults observed during year 3 of the baseline simulation.
Fig 13.
Seasonal abundances of adult sand flies observed during year 3 of the baseline simulation (solid line) and relative numbers of adults caught in light-traps in A) Rasulpur, B) Mahesia, C) Mohammadpur, three villages in Bihar, India (dots, unpublished data from weekly collections used to develop figures and tables in [21]).
Field data were scaled (Rasulpur data x 500; Mahesia data x 280; Mohammadpur data x 450) to facilitate comparison of relative seasonal abundances.
Fig 14.
Comparison of the seasonality of adult sand flies observed during year 3 of simulation for treatments performed once annually January-June (A-F) and the baseline simulation (no treatment) (mean 10 replications).
Black brackets indicate April-August and the red brackets indicate the summer months of peak human exposure (June-August). Red boxes indicate the months of treatment application.
Fig 15.
Comparison of the seasonality of adult sand flies observed during year 3 of simulation for treatments performed once annually July-December (A-F) and the baseline simulation (no treatment) (mean 10 replications).
Black brackets indicate April-August and the red brackets indicate the summer months of peak human exposure (June-August). Red boxes indicate the months of treatment application.
Fig 16.
Comparison of the seasonality of adult sand flies observed during year 3 of simulation for treatments performed three times per year (A-E) and the baseline simulation (no treatment) (mean 10 replications).
Black brackets indicate April-August and the red brackets indicate the summer months of peak human exposure (June-August). Red boxes indicate the months of treatment application.
Fig 17.
Comparison of the seasonality of adult sand flies observed during year 3 of simulation for treatments performed six times per year (A and B) and the baseline simulation (no treatment) (mean 10 replications).
Black brackets indicate April-August and the red brackets indicate the summer months of peak human exposure (June-August). Red boxes indicate the months of treatment application.
Fig 18.
Comparison of the seasonality of adult sand flies observed during a 3-year simulation period for treatments performed 12 times per year and the baseline simulation (no treatment) (mean 10 replications).
Fig 19.
Comparison of (A) the cumulative number of sand fly days over the entire third year of treatment, (B) the cumulative number of sand fly days from April-August of the third year, and (C) the cumulative number of sand fly days from June-August of the third year observed during the indicated treatment scenarios.
The x-axis labels indicate the number of treatments per year and the months in parentheses indicate the month of the first treatment each year. Bars represent means (±1 standard error) of 10 replications and vertical arrows of the same color indicate pairs of control schemes that were not significantly different from one another based on Fisher’s least significant difference (LSD) tests. All other pairwise LSD comparisons between control schemes indicated significant (p < 0.0001) differences.
Fig 20.
Comparison of the seasonality of (A) eggs, (B) larvae, and (C) adult sand flies observed during year 3 of the baseline simulation (no treatment) to the period during which fipronil efficacy is maintained when treatment is applied three times per year (March, May, July).
Vertical red arrows indicate day of application and horizontal red arrows indicate duration of fipronil efficacy (~60 days). Black brackets indicate April-August and the red brackets indicate the summer months of peak human exposure (June-August).