Sarah Ackley

Assessing Measles Transmission in the United States Following a Large Outbreak in California.

The recent increase in measles cases in California may raise questions regarding the continuing success of measles control. To determine whether the dynamics of measles is qualitatively different in comparison to previous years, we assess whether the 2014-2015 measles outbreak associated with an Anaheim theme park is consistent with subcriticality by calculating maximum-likelihood estimates for the effective reproduction numbe given this year’s outbreak, using the Galton-Watson branching process model. We find that the dynamics after the initial transmission event are consistent with prior transmission, but does not exclude the possibilty that the effective reproduction number has increased.

Mortality estimates from ovarian age distributions of the tsetse fly Glossina pallidipes Austen sampled in Zimbabwe suggest the need for new analytical approaches.

Mortality estimates are central to understanding tsetse fly population dynamics, but are difficult to acquire from wild populations. They can be obtained from age distribution data but, with limited data, it is unclear whether the assumptions required to make the estimates are satisfied and, if not, how violations affect the estimates. We evaluate the assumptions required for existing mortality estimation techniques using long-term longitudinal ovarian dissection data from 144,106 female tsetse, Glossina pallidipes Austen, captured in Zimbabwe between 1988 and 1999. At the end of the hot-dry season each year, mean ovarian ages peaked, and maximum-likelihood mortality estimates declined to low levels, contrary to mark-recapture estimates, suggesting violations of the assumptions underlying the estimation technique. We demonstrate that age distributions are seldom stable for G. pallidipes at our study site, and hypothesize that this is a consequence of a disproportionate increase in the mortality of pupae and young adults at the hottest times of the year. Assumptions of age-independent mortality and capture probability are also violated, the latter bias varying with capture method and with pregnancy and nutritional status. As a consequence, mortality estimates obtained from ovarian dissection data are unreliable. To overcome these problems we suggest simulating female tsetse populations, using dynamical modelling techniques that make no assumptions about the stability of the age distribution.

Antibiotic Use as a Tragedy of the Commons: A Cross-Sectional Survey

Background. Many believe antibiotic use results in a tragedy of the commons, since overuse may lead to antibiotic resistance and limiting use would benefit society. In contrast, mass antibiotic treatment programs are thought to result in community-wide benefits. A survey was conducted to learn the views of infectious disease experts on the individual- and societal-level consequences of antibiotic use. Methods. The survey instrument was designed to elicit opinions on antibiotic use and resistance. It was sent via SurveyMonkey to infectious disease professionals identified through literature searches. Descriptive statistics were used to analyze the data. Results. A total of 1,530 responses were received for a response rate of 9.9%. Nearly all participants believed antibiotic use could result in a tragedy of the commons, at least in certain circumstances (96.0%). Most participants did not believe mass antibiotic treatment programs could produce societal benefits in an antibiotic-free society (91.4%) or in the United States (94.2%), though more believed such programs would benefit antibiotic-free societies compared to the United States (P < 0.001). Conclusions. The experts surveyed believe that antibiotic use can result in a tragedy of the commons and do not believe that mass treatment programs benefit individuals or society.

Optimal Seasonal Timing of Oral Azithromycin for Malaria

Mass administration of azithromycin for trachoma has been shown to reduce malarial parasitemia. However, the optimal seasonal timing of such distributions for antimalarial benefit has not been established. We performed numerical analyses on a seasonally forced epidemic model (of Ross-Macdonald type) with periodic impulsive annual mass treatment to address this question. We conclude that when azithromycin-based trachoma elimination programs occur in regions of seasonal malaria transmission, such as Niger, the optimal seasonal timing of mass drug administration (MDA) may not occur during the season of maximum transmission.

A dynamic model for estimating adult female mortality from ovarian dissection data for the tsetse fly Glossina pallidipes Austen sampled in Zimbabwe

Human and animal trypanosomiasis, spread by tsetse flies (Glossina spp), is a major public health concern in much of sub-Saharan Africa. The basic reproduction number of vector-borne diseases, such as trypanosomiasis, is a function of vector mortality rate. Robust methods for estimating tsetse mortality are thus of interest for understanding population and disease dynamics and for optimal control. Existing methods for estimating mortality in adult tsetse, from ovarian dissection data, often use invalid assumptions of the existence of a stable age distribution, and age-invariant mortality and capture probability. We develop a dynamic model to estimate tsetse mortality from ovarian dissection data in populations where the age distribution is not necessarily stable. The models correspond to several hypotheses about how temperature affects mortality: no temperature dependence (model 1), identical temperature dependence for mature adults and immature stages, i.e., pupae and newly emerged adults (model 2), and differential temperature dependence for mature adults and immature stages (model 3). We fit our models to ovarian dissection data for G. pallidipes collected at Rekomitjie Research Station in the Zambezi Valley in Zimbabwe. We compare model fits to determine the most probable model, given the data, by calculating the Akaike Information Criterion (AIC) for each model. The model that allows for a differential dependence of temperature on mortality for immature stages and mature adults (model 3) performs significantly better than models 1 and 2. All models produce mortality estimates, for mature adults, of approximately 3% per day for mean daily temperatures below 25°C, consistent with those of mark-recapture studies performed in other settings. For temperatures greater than 25°C, mortality among immature classes of tsetse increases substantially, whereas mortality remains roughly constant for mature adults. As a sensitivity analysis, model 3 was simultaneously fit to both the ovarian dissection and trap data; while this fit also produces comparable mortality at temperatures below 25°C, it is not possible to obtain good fits to both data sources simultaneously, highlighting the uncertain correspondence between trap catches and population levels and/or the need for further improvements to our model. The modelling approach employed here could be applied to any substantial time series of age distribution data.

The Effect of Contact Investigations and Public Health Interventions in the Control and Prevention of Measles Transmission: A Simulation Study

Background Measles cases continue to occur despite its elimination status in the United States. To control transmission, public health officials confirm the measles diagnosis, identify close contacts of infectious cases, deliver public health interventions (i.e., post-exposure prophylaxis) among those who are eligible, and follow-up with the close contacts to determine overall health outcomes. A stochastic network simulation of measles contact tracing was conducted using existing agent-based modeling software and a synthetic population with high levels of immunity in order to estimate the impact of different interventions in controlling measles transmission. Methods and Findings The synthetic population was created to simulate California`s population in terms of population demographics, household, workplace, school, and neighborhood characteristics using California Department of Finance 2010 census data. Parameters for the model were obtained from a review of the literature, California measles case surveillance data, and expert opinion. Eight different scenarios defined by the use of three different public health interventions were evaluated: (a) post-exposure measles, mumps, and rubella (MMR) vaccine, (b) post-exposure immune globulin (IG), and (c) voluntary isolation and home quarantine in the presence or absence of public health response delays. Voluntary isolation and home quarantine coupled with one or two other interventions had the greatest reduction in the number of secondary cases infected by the index case and the probability of escape situations (i.e., the outbreak continues after 90 days). Conclusions Interrupting contact patterns via voluntary isolation and home quarantine are particularly important in reducing the number of secondary cases infected by the index case and the probability of uncontrolled outbreaks.

Evaluating Subcriticality during the Ebola Epidemic in West Africa

The 2014–2015 Ebola outbreak is the largest and most widespread to date. In order to estimate ongoing transmission in the affected countries, we estimated the weekly average number of secondary cases caused by one individual infected with Ebola throughout the infectious period for each affected West African country using a stochastic hidden Markov model fitted to case data from the World Health Organization. If the average number of infections caused by one Ebola infection is less than 1.0, the epidemic is subcritical and cannot sustain itself. The epidemics in Liberia and Sierra Leone have approached subcriticality at some point during the epidemic; the epidemic in Guinea is ongoing with no evidence that it is subcritical. Response efforts to control the epidemic should continue in order to eliminate Ebola cases in West Africa.

Incidence of and risk factors for developing idiopathic macular hole among a diverse group of patients throughout the United States

Importance Idiopathic macular holes (MHs) are a cause of decreased vision among older Americans. A better understanding of risk factors for MH may help clarify the pathophysiologic factors of MH and identify potential new avenues for preventing and treating idiopathic MHs. Objective To determine the incidence of and risk factors associated with the development of idiopathic MH requiring surgical repair with vitrectomy among a large group of managed care plan beneficiaries throughout the United States. Design, Setting, and Participants A retrospective, longitudinal cohort study was conducted of all beneficiaries 40 years or older who were continuously enrolled for 3 or more years in a nationwide US managed care network between January 1, 2001, and December 31, 2012, who had 2 or more visits to an eye care professional. The managed care network was queried starting in 2009, and data analysis was conducted from December 1, 2014, to August 15, 2016. Main Outcomes and Measures Development of idiopathic MH requiring surgical repair with vitrectomy. Results Of the 659 357 enrollees who met inclusion criteria (391 674 females and 267 683 males; mean [SD] age, 56.2 [9.2] years), 144 (0.02%) developed an MH requiring vitrectomy. After adjusting for confounding factors, females had a 64% increased risk of developing MH compared with males (adjusted hazard ratio, 1.64; 95% CI, 1.11-2.43; P = .01), with the effect of sex varying across ages. Compared with white participants, Asian-American enrollees had a 177% increased risk of developing MH (adjusted hazard ratio, 2.77; 95% CI, 1.27-6.02; P = .01). Conclusions and Relevance In this large cohort, sex was confirmed to be associated with developing an MH requiring vitrectomy; the effect varies across ages differently for females vs males. These differences may be the basis for the underlying pathophysiologic factors contributing to the development of MH.

Modeling historical tuberculosis epidemics among Canadian First Nations: effects of malnutrition and genetic variation

Late 19th century epidemics of tuberculosis (TB) in Western Canadian First Nations resulted in peak TB mortality rates more than six times the highest rates recorded in Europe. Using a mathematical modeling approach and historical TB mortality time series, we investigate potential causes of high TB mortality and rapid epidemic decline in First Nations from 1885 to 1940. We explore two potential causes of dramatic epidemic dynamics observed in this setting: first, we explore effects of famine prior to 1900 on both TB and population dynamics. Malnutrition is recognized as an individual-level risk factor for TB progression and mortality; its population-level effects on TB epidemics have not been explored previously. Second, we explore effects of heterogeneity in susceptibility to TB in two ways: modeling heterogeneity in susceptibility to infection, and heterogeneity in risk of developing disease once infected. Our results indicate that models lacking famine-related changes in TB parameters or heterogeneity result in an implausibly poor fit to both the TB mortality time series and census data; the inclusion of these features allows for the characteristic decline and rise in population observed in First Nations during this time period and confers improved fits to TB mortality data.

Continuously tunable modulation scheme for precision control of optical cavities with variable detuning

We present a scheme for locking optical cavities with arbitrary detuning by many linewidths from resonance using an electro-optic modulator that can provide arbitrary ratios of amplitude-to-phase modulation. We demonstrate our scheme on a Fabry-Perot cavity, and show that a well-behaved linear error signal can be obtained by demodulating the reflected light from a cavity that is detuned by several linewidths.