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Introduction
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July 2003 - present
October 1999 - July 2003
October 1999 - July 2003
Education
October 1992 - October 1996
October 1988 - June 1991
Publications
Publications (252)
Current knowledge of dengue virus (DENV) transmission provides only a partial understanding of a complex and dynamic system yielding a public health track record that has more failures than successes. An important part of the problem is that the foundation for contemporary interventions includes a series of longstanding, but untested, assumptions b...
Transmission heterogeneity, whereby a disproportionate fraction of pathogen transmission events result from a small number of individuals or geographic locations, is an inherent property of many, if not most, infectious disease systems. For vector-borne diseases, transmission heterogeneity is inferred from the distribution of the number of vectors...
The importance of mosquitoes in human pathogen transmission has motivated major research efforts into mosquito biology in pursuit of more effective vector control measures. Aedes aegypti is a particular concern in tropical urban areas, where it is the primary vector of numerous flaviviruses, including the yellow fever, Zika, and dengue viruses. Wit...
Background:
Evidence seems to suggest that the risk of Coronavirus Disease 2019 (COVID-19) might vary across communities due to differences in population characteristics and movement patterns. However, little is known about these differences in the greater St Louis Area of Missouri and yet this information is useful for targeting control efforts....
Many pathogens spread via environmental transmission, without requiring host-to-host direct contact. While models for environmental transmission exist, many are simply constructed intuitively with structures analogous to standard models for direct transmission. As model insights are generally sensitive to the underlying model assumptions, it is imp...
The mosquito Aedes aegypti is the vector of a number of medically-important viruses, including dengue virus, yellow virus, chikungunya virus, and Zika virus, and as such vector control is a key approach to managing the diseases they cause. Understanding the impact of vector control on these diseases is aided by first understanding its impact on Ae....
Background
There is evidence of geographic disparities in COVID-19 hospitalization risks that, if identified, could guide control efforts. Therefore, the objective of this study was to investigate Zip Code Tabulation Area (ZCTA)-level geographic disparities and identify predictors of COVID-19 hospitalization risks in the St. Louis area.
Methods
Ho...
Many pathogens spread via environmental transmission, without requiring host-to-host direct contact. While models for environmental transmission exist, many are simply constructed intuitively with structures analogous to standard models for direct transmission. As model insights are generally sensitive to the underlying model assumptions, it is imp...
Background: Evidence suggests that the risk of Coronavirus Disease 2019 (COVID-19) varies geographically due to differences in population characteristics. Therefore, the objectives of this study were to identify: (a) geographic disparities of COVID-19 risk in the Greater St. Louis area of Missouri, USA; (b) predictors of the identified disparities....
Background: COVID-19 has overwhelmed the US healthcare system, with over 44 million cases and over 700,000 deaths as of October 6, 2021. There is evidence that some communities are disproportionately affected. This may result in geographic disparities in COVID-19 hospitalization risk that, if identified, could guide control efforts. Therefore, the...
The importance of mosquitoes in human pathogen transmission has motivated major research efforts into mosquito biology in pursuit of more effective vector control measures. Aedes aegypti is a particular concern in tropical urban areas, where it is the primary vector of numerous flaviviruses, including the yellow fever, Zika, and dengue viruses. Wit...
This study describes the evolution of knockdown resistance (kdr) haplotypes in Aedes aegypti in response to pyrethroid insecticide use over the course of 18 years in Iquitos, Peru. Based on the duration and intensiveness of sampling (~10,000 samples), this is the most thorough study of kdr population genetics in Ae. aegypti to date within a city. W...
Introduction
One genetic approach to insect pest management aims to suppress or locally eliminate a species through large, repeated releases of genetically engineered strains that render female offspring unviable. Strains with this female‐killing characteristic have been developed either with all molecular components in a single construct or in two...
Introduced rodent populations pose significant threats worldwide, with particularly severe impacts on islands. Advancements in genome editing have motivated interest in synthetic gene drives that could potentially provide efficient and localized suppression of invasive rodent populations. Application of such technologies will require rigorous popul...
The SARS-CoV-2 variant B.1.1.7 reportedly exhibits substantially higher transmission than the ancestral strain and may generate a major surge of cases before vaccines become widely available, while the P.1 and B.1.351 variants may be equally transmissible and also resist vaccines. All three variants can be sensitively detected by RT-PCR due to an o...
This study describes the evolution of knockdown resistance (kdr) haplotypes in Aedes aegypti in response to pyrethroid insecticide use over the course of 18 years in Iquitos, Peru. Based on the duration and intensiveness of sampling (~10,000 samples), this is the most thorough study of kdr population genetics in Ae. aegypti to date within a city. W...
Heterogeneous exposure to mosquitoes determines an individual’s contribution to vector-borne pathogen transmission. Particularly for dengue virus (DENV), there is a major difficulty in quantifying human-vector contacts due to the unknown coupled effect of key heterogeneities. To test the hypothesis that the reduction of human out-of-home mobility d...
The SARS-CoV-2 variant B.1.1.7 reportedly exhibits substantially higher transmission than the ancestral strain and may generate a major surge of cases before vaccines become widely available. As B.1.1.7 can be sensitively detected using the Thermo Fisher TaqPath S-gene RT-PCR test, contact tracing and isolation programs appear well-suited to slowin...
Contact tracing is critical to controlling COVID-19, but most protocols only “forward-trace” to notify people who were recently exposed. Using a stochastic branching-process model, we find that “bidirectional” tracing to identify infector individuals and their other infectees robustly improves outbreak control. In our model, bidirectional tracing m...
Controlling the regional re-emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after its initial spread in ever-changing personal contact networks and disease landscapes is a challenging task. In a landscape context, contact opportunities within and between populations are changing rapidly as lockdown measures are relaxed and...
The spread of synthetic gene drives is often discussed in the context of panmictic populations connected by gene flow and described with simple deterministic models. Under such assumptions, an entire species could be altered by releasing a single individual carrying an invasive gene drive, such as a standard homing drive. While this remains a theor...
The lack of effective vaccines for many endemic diseases often forces policymakers to rely on non-immunizing control measures, such as vector control, to reduce the massive burden of these diseases. Controls can have well-known counterintuitive effects on endemic infections, including the honeymoon effect, in which partially effective controls caus...
Robust methods of predicting how gene drive systems will interact with ecosystems is essential for safe deployment of gene drive technology. We describe how quantitative tools can reduce risk uncertainty, streamline empirical research, guide risk management, and promote cross-sector collaboration throughout the process of gene drive technology deve...
Controlling the regional re-emergence of SARS-CoV-2 after its initial spread in ever-changing personal contact networks and disease landscapes is a challenging task. In a landscape context, contact opportunities within and between populations are changing rapidly as lockdown measures are relaxed and a number of social activities re-activated. Using...
Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but th...
Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced in countries worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement lockdown exit strategies that allow restrictions to be relaxed while attempting to control the risk of a surge in cases. Mathematical modelling has played a central r...
Contact tracing is critical to limiting the spread of pandemics such as COVID-19, but most protocols only "forward-trace" to notify people who were recently exposed. Using a stochastic branching process model, we find that "bidirectional" tracing to identify infector individuals robustly outperforms forward-only approaches across a wide range of sc...
The spread of synthetic gene drives is often discussed in the context of panmictic populations connected by gene flow and described with simple deterministic models. Under such assumptions, an entire species could be altered by releasing a single individual carrying an invasive gene drive, such as a standard homing drive. While this remains a theor...
Recent years have seen rising incidence of dengue and large outbreaks of Zika and chikungunya, which are all caused by viruses transmitted by Aedes aegypti mosquitoes. In most settings, the primary intervention against Aedes-transmitted viruses is vector control, such as indoor, ultra-low volume (ULV) spraying. Targeted indoor residual spraying (TI...
We propose an algorithm to select parameter subset combinations that can be estimated using an ordinary least-squares (OLS) inverse problem formulation with a given data set. First, the algorithm selects the parameter combinations that correspond to sensitivity matrices with full rank. Second, the algorithm involves uncertainty quantification by us...
We consider a single outbreak susceptible-infected-recovered (SIR) model and corresponding estimation procedures for the effective reproductive number $\mathcal{R}(t)$. We discuss the estimation of the underlying SIR parameters with a generalized least squares (GLS) estimation technique. We do this in the context of appropriate statistical models f...
Many novel genetic approaches are under development to combat insect pests, which continue to impose substantial burdens in the forms of transmission of vector-borne disease and the reduction of agricultural yields. One category of genetic pest management aims to suppress or locally eliminate a species through large, repeated releases of fertile ma...
The Asian tiger mosquito, Aedes (Stegomyia) albopictus (Skuse), is a peridomestic, container-ovipositing mosquito commonly found throughout the southeastern United States. In the United States, Ae. albopictus is typically considered a nuisance pest; however, it is capable of transmitting multiple pathogens. Ae. albopictus is an important pest speci...
In mathematical epidemiology, a well-known formula describes the impact of heterogeneity on the basic reproductive number, R0, for situations in which transmission is separable and for which there is one source of variation in susceptibility and one source of variation in infectiousness. This formula is written in terms of the magnitudes of the het...
Invasive rodents impact biodiversity, human health and food security worldwide. The biodiversity impacts are particularly significant on islands, which are the primary sites of vertebrate extinctions and where we are reaching the limits of current control technologies. Gene drives may represent an effective approach to this challenge, but knowledge...
Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach,...
In mathematical epidemiology, a well-known formula describes the impact of heterogeneity on the basic reproductive number, R 0 , for situations in which transmission is separable and for which there is one source of variation in susceptibility and one source of variation in infectiousness. This formula is written in terms of the magnitudes of the h...
Recent years have seen rising incidence of dengue and large outbreaks of Zika and chikungunya, which are all caused by viruses transmitted by Aedes aegypti mosquitoes. In most settings, the primary intervention against Aedes -transmitted viruses is vector control, such as indoor, ultra-low volume (ULV) spraying. Targeted indoor residual spraying (T...
Optimism regarding potential epidemiological and conservation applications of modern gene drives is tempered by concern about the possibility of unintended spread of engineered organisms beyond the target population. In response, several novel gene drive approaches have been proposed that can, under certain conditions, locally alter characteristics...
The lack of effective vaccines for many endemic diseases often forces policymakers to enact control programs that rely on non-immunizing controls, such as vector control, in order to reduce the massive burden of these diseases. It is well known that controls can have counterintuitive effects, such as the honeymoon effect, in which partially effecti...
Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to suppress a population provide an alternative approach, b...
Many systems arising in biological applications are subject to periodic forcing. In these systems the forcing parameter is not only time-varying but also known to have a periodic structure. We present an approach to estimate periodic, time-varying parameters using nonlinear Bayesian filtering. Most parameter estimation methodology in the literature...
Despite estimates that, each year, as many as 300 million dengue virus (DENV) infections result in either no perceptible symptoms (asymptomatic) or symptoms that are sufficiently mild to go undetected by surveillance systems (inapparent), it has been assumed that these infections contribute little to onward transmission. However, recent blood-feedi...
Cohort studies addressing (As+IS): AS ratios in primary (1°), secondary (2°) infections, and post-2° infections.
Studies for 1° and 2° were collated in [23]. Studies used for post-2° [22,28] were derived from [7]. N.S. = not stated.
(XLSX)
Data from direct feeding experiment [16] used to inform viremia to infectiousness relationship.
(XLSX)
Mean contribution of infection classes to total force of infection (FoI) for Thailand.
The contribution to the total FoI of a class is derived from the ratio between FoI attributable to this class and total FoI, as in Eq (1). The respective net infectiousness is derived from the 3,000 random samples displayed in Fig 3. The infections are further di...
Variance-based sensitivity analysis.
The contribution to the variance represents the total effect index, denoting the contribution of each source of uncertainty to the total variance, including its interactions. (IIP = intrinsic incubation period).
(PDF)
Pre-exposure profile as a function of the force of infection for (a) Brazil, (b) Thailand.
The seroprevalence of the population is estimated using a system of ordinary differential equations with state variables denoting the proportion of the population pre-exposed to 0–4 serotypes. Transition to pre-exposure state i occurs at a rate (4-i)FoI. Indi...
Mean contribution of infection classes to total FoI in an emerging setting.
The contribution to the total FoI of a class is derived from the ratio between FoI attributable to this class and total FoI, as in Eq (1). The respective net infectiousness is derived from the 3,000 random samples displayed in Fig 3. The infections are further distributed a...
Assessment of model assumptions and limitations.
(PDF)
Assessment of infectiousness data.
(PDF)
Probabilistic comparison of net infectiousness uncertainty distributions.
(PDF)
Mean contribution of infection classes to total force of infection (FoI) when accounting for the contribution of post-secondary infections to transmission.
The contribution to the total FoI of a class is derived from the ratio between FoI attributable to this class and total FoI, as in Eq (1). The respective net infectiousness is derived from the 3...
Background
Aedes aegypti is a primary vector of dengue, chikungunya, Zika, and urban yellow fever viruses. Indoor, ultra low volume (ULV) space spraying with pyrethroid insecticides is the main approach used for Ae. aegypti emergency control in many countries. Given the widespread use of this method, the lack of large-scale experiments or detailed...
Histogram of AA/HSE at baseline (C1).
Rows show treatment sector. X-axis is sqrt-scaled. The majority of house surveys find no adults.
(PDF)
Model results, as in Fig 4.
All models include fixed effects of sector and circuit, with a separate model for each year. (A) Counts: negative binomial GLM (NB-GLM). (B) Proportions: logistic GLM (L-GLM). Note that Breteau Index (BI) = 100*PC/HSE. See also S2–S10 Tables.
(PDF)
Observation counts by circuit.
Weeks: Week number from experiment start. Houses: number of unique houses surveyed. Surveys: total surveys (either adult, or combined adults and immature). Full surveys: surveys where both adult and immatures were surveyed. Buffer, Spray: surveys in buffer and spray sector, respectively.
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All supporting tables and figures.
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Maps of experimental areas, showing satellite imagery.
Note the scale differs between experiments. See also Fig 1.
(PDF)
Comparison between spray status (whether house was sprayed prior to survey).
Ratio of AA/HSE in houses that were either sprayed or not sprayed prior to surveying (no prior spray/prior spray). Bold p-values: In L-2014, houses without prior spraying yielded significantly more adults than houses with prior spraying. In S-2013, most houses were sprayed...
Effect of prior spray on AA/HSE.
A single model (NB-GLM) includes both experiment year and spray status as predictors. Group: significance groups (Tukey HSD) compare among all rows. Only house surveys in the spray sector during experimental spraying are included (i.e., S-2013 C2 and L-2014 C6). Not all sprayed houses were subsequently surveyed. The...
Proportion nulliparous Aedes aegypti females (PrNF).
(A) S-2013. (B) L-2014. Model estimates by circuit and treatment sector. Horizontal line separates treatment sectors, significance groups (Tukey HSD) compare among all rows. See S5 Fig.
(PDF)
Time series of survey results, aggregated by week.
X-axis shows week start date. Color and line-type shows treatment sector (orange triangle: spray sector). Point size shows number of surveyed houses. Vertical lines show approximately spray dates: dashed, experimental spraying (spray sector only); dotted, citywide spraying (February 2014, all secto...
Maps of spray events (red) by spray cycle (rows).
(A) S-2013. (B) L-2014. During L-2014, in addition to experimental spraying, 3 cycles of emergency citywide spraying were conducted. Note the map scale differs between A and B. See also Fig 1.
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Comparison between sectors (within time).
Ratio of AA/HSE in spray sector relative to buffer sector (spray/buffer). Bold p-values: significant difference between sectors. In both years, the spray sector starts with more adults per house, and spraying reduces AA/HSE relative to buffer sectors. As in S3 Table, the effects of spraying are more pronoun...
Comparison between times (within spray sector).
Ratio of AA/HSE relative to baseline (C1, spray sector only). Bold p-values: significant difference from baseline circuit. In both years, spraying reduces AA/HSE relative to baseline (C1). The effects of spraying are most pronounced in S-2013, but are short-lived in both years. See also Fig 4A.
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Proportion of Aedes aegypti adult-infected houses (PrIH).
(A) S-2013. (B) L-2014. Model estimates by circuit and treatment sector. Horizontal line separates treatment sectors, significance groups (Tukey HSD) compare among all rows. See Fig 4B for model description.
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Proportion Aedes aegypti positive containers (PrPC).
(A) S-2013. (B) L-2014. Model estimates by circuit and treatment sector. Horizontal line separates treatment sectors, significance groups (Tukey HSD) compare among all rows. No container surveys were conducted during spraying See also S5 Fig.
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Summary of spray coverage in S-2013 (A) and L-2014 (B). In both years, most houses were sprayed in at least 5 out of 6 spray cycles, while a small number of houses were never sprayed. In L-2014, experimental spray coverage was much higher than emergency (citywide) spray coverage.
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Boxplot of control cage house means: 25 adults per cage, 4 cages per house, approximately 5 houses per spray cycle.
Insects were from a laboratory colony (one colony per year).
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