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1.  Estimated Deaths and Illnesses Averted During Fungal Meningitis Outbreak Associated with Contaminated Steroid Injections, United States, 2012–2013 
Emerging Infectious Diseases  2015;21(6):933-940.
Public health response to the outbreak likely resulted fewer injections, cases, and deaths.
Deaths, Illnesses Averted in Meningitis Outbreak
During 2012–2013, the US Centers for Disease Control and Prevention and partners responded to a multistate outbreak of fungal infections linked to methylprednisolone acetate (MPA) injections produced by a compounding pharmacy. We evaluated the effects of public health actions on the scope of this outbreak. A comparison of 60-day case-fatality rates and clinical characteristics of patients given a diagnosis on or before October 4, the date the outbreak was widely publicized, with those of patients given a diagnosis after October 4 showed that an estimated 3,150 MPA injections, 153 cases of meningitis or stroke, and 124 deaths were averted. Compared with diagnosis after October 4, diagnosis on or before October 4 was significantly associated with a higher 60-day case-fatality rate (28% vs. 5%; p<0.0001). Aggressive public health action resulted in a substantially reduced estimated number of persons affected by this outbreak and improved survival of affected patients.
PMCID: PMC4451895  PMID: 25989264
Meningitis; fungal; disease outbreaks; disease modeling; fungi; deaths; illness; public health response; contaminated steroid injections; United States
2.  Microneedle Patches: Usability and Acceptability for Self-Vaccination against Influenza 
Vaccine  2014;32(16):1856-1862.
While therapeutic drugs are routinely self-administered by patients, there is little precedent for self-vaccination. Convenient self-vaccination may expand vaccination coverage and reduce administration costs. Microneedle patches are in development for many vaccines, but no reports exist on usability or acceptability. We hypothesized that naïve patients could apply patches and that self-administered patches would improve stated intent to receive an influenza vaccine. We conducted a randomized, repeated measures study with 91 venue-recruited adults. To simulate vaccination, subjects received placebo microneedle patches given three times by self-administration and once by the investigator, as well as an intramuscular injection of saline. Seventy participants inserted patches with thumb pressure alone and the remainder used snap-based devices that closed shut at a certain force. Usability was assessed by skin staining and acceptability was measured with an adaptive-choice analysis. The best usability was seen with the snap device, with users inserting a median value of 93–96% of microneedles over three repetitions. When a self-administered microneedle patch was offered, intent to vaccinate increased from 44% to 65% (CI: 55–74%). The majority of those intending vaccination would prefer to self-vaccinate: 64% (CI: 51–75%). There were no serious adverse events associated with use of microneedle patches. The findings from this initial study indicate that microneedle patches for self-vaccination against influenza are usable and may lead to improved vaccination coverage.
PMCID: PMC3979961  PMID: 24530146
microneedle; human study; usability; acceptability; influenza
3.  Initial and Long-Term Costs of Patients Hospitalized with West Nile Virus Disease 
There are no published data on the economic burden for specific West Nile virus (WNV) clinical syndromes (i.e., fever, meningitis, encephalitis, and acute flaccid paralysis [AFP]). We estimated initial hospital and lost-productivity costs from 80 patients hospitalized with WNV disease in Colorado during 2003; 38 of these patients were followed for 5 years to determine long-term medical and lost-productivity costs. Initial costs were highest for patients with AFP (median $25,117; range $5,385–$283,381) and encephalitis (median $20,105; range $3,965–$324,167). Long-term costs were highest for patients with AFP (median $22,628; range $624–$439,945) and meningitis (median $10,556; range $0–$260,748). Extrapolating from this small cohort to national surveillance data, we estimated the total cumulative costs of reported WNV hospitalized cases from 1999 through 2012 to be $778 million (95% confidence interval $673 million–$1.01 billion). These estimates can be used in assessing the cost-effectiveness of interventions to prevent WNV disease.
PMCID: PMC3945683  PMID: 24515937
4.  Estimating Influenza Disease Burden from Population-Based Surveillance Data in the United States 
PLoS ONE  2015;10(3):e0118369.
Annual estimates of the influenza disease burden provide information to evaluate programs and allocate resources. We used a multiplier method with routine population-based surveillance data on influenza hospitalization in the United States to correct for under-reporting and estimate the burden of influenza for seasons after the 2009 pandemic. Five sites of the Influenza Hospitalization Surveillance Network (FluSurv-NET) collected data on the frequency and sensitivity of influenza testing during two seasons to estimate under-detection. Population-based rates of influenza-associated hospitalization and Intensive Care Unit admission from 2010–2013 were extrapolated to the U.S. population from FluSurv-NET and corrected for under-detection. Influenza deaths were calculated using a ratio of deaths to hospitalizations. We estimated that influenza-related hospitalizations were under-detected during 2010-11 by a factor of 2.1 (95%CI 1.7–2.9) for age < 18 years, 3.1 (2.4–4.5) for ages 18-64 years, and 5.2 (95%CI 3.8–8.3) for age 65+. Results were similar in 2011-12. Extrapolated estimates for 3 seasons from 2010–2013 included: 114,192–624,435 hospitalizations, 18,491–95,390 ICU admissions, and 4,915–27,174 deaths per year; 54–70% of hospitalizations and 71–85% of deaths occurred among adults aged 65+. Influenza causes a substantial disease burden in the U.S. that varies by age and season. Periodic estimation of multipliers across multiple sites and age groups improves our understanding of influenza detection in sentinel surveillance systems. Adjusting surveillance data using a multiplier method is a relatively simple means to estimate the impact of influenza and the subsequent value of interventions to prevent influenza.
PMCID: PMC4349859  PMID: 25738736
5.  Regional Spread of Ebola Virus, West Africa, 2014 
Emerging Infectious Diseases  2015;21(3):444-447.
To explain the spread of the 2014 Ebola epidemic in West Africa, and thus help with response planning, we analyzed publicly available data. We found that the risk for infection in an area can be predicted by case counts, population data, and distances between affected and nonaffected areas.
PMCID: PMC4344291  PMID: 25693782
Ebola virus; hemorrhagic fever; Ebola; Ebola virus disease; epidemics; models; statistical models; geographic information systems; GIS; spatial analysis
6.  Effects of Vaccine Program against Pandemic Influenza A(H1N1) Virus, United States, 2009–2010 
Emerging Infectious Diseases  2013;19(3):439-448.
Vaccination likely prevented 700,000–1,500,000 clinical cases, 4,000–10,000 hospitalizations, and 200–500 deaths.
In April 2009, the United States began a response to the emergence of a pandemic influenza virus strain: A(H1N1)pdm09. Vaccination began in October 2009. By using US surveillance data (April 12, 2009–April 10, 2010) and vaccine coverage estimates (October 3, 2009–April 18, 2010), we estimated that the A(H1N1)pdm09 virus vaccination program prevented 700,000–1,500,000 clinical cases, 4,000–10,000 hospitalizations, and 200–500 deaths. We found that the national health effects were greatly influenced by the timing of vaccine administration and the effectiveness of the vaccine. We estimated that recommendations for priority vaccination of targeted priority groups were not inferior to other vaccination prioritization strategies. These results emphasize the need for relevant surveillance data to facilitate a rapid evaluation of vaccine recommendations and effects.
PMCID: PMC3647645  PMID: 23622679
Influenza; viruses; vaccine; vaccination; A(H1N1)pdm09; H1N1; pandemic; model
7.  Estimating Effect of Antiviral Drug Use during Pandemic (H1N1) 2009 Outbreak, United States 
Emerging Infectious Diseases  2011;17(9):1591-1598.
From April 2009 through March 2010, during the pandemic (H1N1) 2009 outbreak, ≈8.2 million prescriptions for influenza neuraminidase-inhibiting antiviral drugs were filled in the United States. We estimated the number of hospitalizations likely averted due to use of these antiviral medications. After adjusting for prescriptions that were used for prophylaxis and personal stockpiles, as well as for patients who did not complete their drug regimen, we estimated the filled prescriptions prevented ≈8,400–12,600 hospitalizations (on the basis of median values). Approximately 60% of these prevented hospitalizations were among adults 18–64 years of age, with the remainder almost equally divided between children 0–17 years of age and adults >65 years of age. Public health officials should consider these estimates an indication of success of treating patients during the 2009 pandemic and a warning of the need for renewed planning to cope with the next pandemic.
PMCID: PMC3358088  PMID: 21888783
antiviral drugs; hospitalizations; impact; influenza; pandemic; pandemic (H1N1) 2009; research; respiratory infections; United States; viruses
8.  Efficiency of Points of Dispensing for Influenza A(H1N1)pdm09 Vaccination, Los Angeles County, California, USA, 2009 
Emerging Infectious Diseases  2014;20(4):590-595.
During October 23–December 8, 2009, the Los Angeles County Department of Public Health used points of dispensing (PODs) to improve access to and increase the number of vaccinations against influenza A(H1N1)pdm09. We assessed the efficiency of these units and access to vaccines among ethnic groups. An average of 251 persons per hour (SE 65) were vaccinated at the PODs; a 10% increase in use of live-attenuated monovalent vaccines reduced that rate by 23 persons per hour (SE 7). Vaccination rates were highest for Asians (257/10,000 persons), followed by Hispanics (114/10,000), whites (75/100,000), and African Americans (37/10,000). Average distance traveled to a POD was highest for whites (6.6 miles; SD 6.5) and lowest for Hispanics (4.7 miles; SD ±5.3). Placing PODs in areas of high population density could be an effective strategy to reach large numbers of persons for mass vaccination, but additional PODs may be needed to improve coverage for specific populations.
PMCID: PMC3966367  PMID: 24656212
H1N1; mass vaccination; points of dispensing; throughput; access; influenza; pandemic; influenza A(H1N1)pdm09; pH1N1; vaccination; vaccine; immunization; California; United States
9.  Laboratory Surge Capacity and Pandemic Influenza 
Emerging Infectious Diseases  2010;16(1):8-13.
PMCID: PMC2874389  PMID: 20031064
Laboratory; testing; capacity; pandemic influenza; influenza; virus; public health; commentary
10.  Cost-Effectiveness of Alternative Strategies for Annual Influenza Vaccination among Children Aged 6 Months to 14 Years in Four Provinces in China 
PLoS ONE  2014;9(1):e87590.
To support policy making, we developed an initial model to assess the cost-effectiveness of potential strategies to increase influenza vaccination rates among children in China.
We studied on children aged 6 months to 14 years in four provinces (Shandong, Henan, Hunan, and Sichuan), with a health care system perspective. We used data from 2005/6 to 2010/11, excluding 2009/10. Costs are reported in 2010 U.S. dollars.
In comparison with no vaccination, the mean (range) of Medically Attended Cases averted by the current self-payment policy for the two age groups (6 to 59 months and 60 months to 14 years) was 1,465 (23∼11,132) and 792 (36∼4,247), and the cost effectiveness ratios were $ 0 (-11-51) and $ 37 (6-125) per case adverted, respectively. In comparison with the current policy, the incremental cost effectiveness ratio (ICER) of alternative strategies, OPTION One-reminder and OPTION Two-comprehensive package, decreased as vaccination rate increased. The ICER for children aged 6 to 59 months was lower than that for children aged 60 months to 14 years.
The model is a useful tool in identifying elements for evaluating vaccination strategies. However, more data are needed to produce more accurate cost-effectiveness estimates of potential vaccination policies.
PMCID: PMC3909220  PMID: 24498145
11.  The Mystery of Increased Hospitalizations of Elderly Patients 
Emerging Infectious Diseases  2008;14(5):727-33.
PMCID: PMC2600238  PMID: 18439380
Hospitalizations; elderly; pneumonia; community-acquired staphyloccal pneumonia; commentary
12.  Pandemic Influenza, Reopening Schools, and Returning to Work 
Emerging Infectious Diseases  2008;14(3):365-72.
Pandemic Influenza, Reopening Schools, and Returning to Work
In this issue of Emerging Infectious Diseases, Victoria Davey and Robert Glass present a paper (1) in which they consider the question of when to “switch off” community-based interventions designed to reduce the spread of pandemic influenza. These authors attempt to answers questions such as when it would be optimal to reopen schools that have been closed as part of a nonpharmaceutical, communitywide influenza mitigation strategy.
PMCID: PMC2570811  PMID: 18325276
Influenza pandemic; mathematical models; reopening schools; returning to work; commentary
13.  Modeling the Effect of Water, Sanitation, and Hygiene and Oral Cholera Vaccine Implementation in Haiti 
In 2010, toxigenic Vibrio cholerae was newly introduced to Haiti. Because resources are limited, decision-makers need to understand the effect of different preventive interventions. We built a static model to estimate the potential number of cholera cases averted through improvements in coverage in water, sanitation and hygiene (WASH) (i.e., latrines, point-of-use chlorination, and piped water), oral cholera vaccine (OCV), or a combination of both. We allowed indirect effects and non-linear relationships between effect and population coverage. Because there are limited incidence data for endemic cholera in Haiti, we estimated the incidence of cholera over 20 years in Haiti by using data from Malawi. Over the next two decades, scalable WASH interventions could avert 57,949–78,567 cholera cases, OCV could avert 38,569–77,636 cases, and interventions that combined WASH and OCV could avert 71,586–88,974 cases. Rate of implementation is the most influential variable, and combined approaches maximized the effect.
PMCID: PMC3795092  PMID: 24106189
15.  Economics of Malaria Prevention in US Travelers to West Africa 
Costs and benefits of malaria prevention are provided during domestic pretravel health consultations. Healthcare payers always, and travelers often, save money when travelers adhere to malaria recommendations and prophylactic regimens in West Africa, especially for longer durations of travel.
Background. Pretravel health consultations help international travelers manage travel-related illness risks through education, vaccination, and medication. This study evaluated costs and benefits of that portion of the health consultation associated with malaria prevention provided to US travelers bound for West Africa.
Methods. The estimated change in disease risk and associated costs and benefits resulting from traveler adherence to malaria chemoprophylaxis were calculated from 2 perspectives: the healthcare payer's and the traveler's. We used data from the Global TravEpiNet network of US travel clinics that collect de-identified pretravel data for international travelers. Disease risk and chemoprophylaxis effectiveness were estimated from published medical reports. Direct medical costs were obtained from the Nationwide Inpatient Sample and published literature.
Results. We analyzed 1029 records from January 2009 to January 2011. Assuming full adherence to chemoprophylaxis regimens, consultations saved healthcare payers a per-traveler average of $14 (9-day trip) to $372 (30-day trip). For travelers, consultations resulted in a range of net cost of $20 (9-day trip) to a net savings of $32 (30-day trip). Differences were mostly driven by risk of malaria in the destination country.
Conclusions. Our model suggests that healthcare payers save money for short- and longer-term trips, and that travelers save money for longer trips when travelers adhere to malaria recommendations and prophylactic regimens in West Africa. This is a potential incentive to healthcare payers to offer consistent pretravel preventive care to travelers. This financial benefit complements the medical benefit of reducing the risk of malaria.
PMCID: PMC3864498  PMID: 24014735
costs; benefits; malaria prevention; pretravel health consultation
16.  Interdisciplinary Public Health Reasoning and Epidemic Modelling: The Case of Black Death 
Emerging Infectious Diseases  2006;12(2):361-362.
PMCID: PMC3373092
epidemic modeling; mathematical modeling; black death; plague; book review
17.  Syndromic Surveillance in Bioterrorist Attacks 
Emerging Infectious Diseases  2005;11(9):1396-400.
PMCID: PMC3310639  PMID: 16673516
syndromic surveillance; bioterrorist; anthrax; commentary
18.  Influenza Illness and Hospitalizations Averted by Influenza Vaccination in the United States, 2005–2011 
PLoS ONE  2013;8(6):e66312.
The goal of influenza vaccination programs is to reduce influenza-associated disease outcomes. Therefore, estimating the reduced burden of influenza as a result of vaccination over time and by age group would allow for a clear understanding of the value of influenza vaccines in the US, and of areas where improvements could lead to greatest benefits.
To estimate the direct effect of influenza vaccination in the US in terms of averted number of cases, medically-attended cases, and hospitalizations over six recent influenza seasons.
Using existing surveillance data, we present a method for assessing the impact of influenza vaccination where impact is defined as either the number of averted outcomes or as the prevented disease fraction (the number of cases estimated to have been averted relative to the number of cases that would have occurred in the absence of vaccination).
We estimated that during our 6-year study period, the number of influenza illnesses averted by vaccination ranged from a low of approximately 1.1 million (95% confidence interval (CI) 0.6–1.7 million) during the 2006–2007 season to a high of 5 million (CI 2.9–8.6 million) during the 2010–2011 season while the number of averted hospitalizations ranged from a low of 7,700 (CI 3,700–14,100) in 2009–2010 to a high of 40,400 (CI 20,800–73,000) in 2010–2011. Prevented fractions varied across age groups and over time. The highest prevented fraction in the study period was observed in 2010–2011, reflecting the post-pandemic expansion of vaccination coverage.
Influenza vaccination programs in the US produce a substantial health benefit in terms of averted cases, clinic visits and hospitalizations. Our results underscore the potential for additional disease prevention through increased vaccination coverage, particularly among nonelderly adults, and increased vaccine effectiveness, particularly among the elderly.
PMCID: PMC3686813  PMID: 23840439
19.  Effect of Winter School Breaks on Influenza-like Illness, Argentina, 2005–2008 
Emerging Infectious Diseases  2013;19(6):938-944.
School closures are used to reduce seasonal and pandemic influenza transmission, yet evidence of their effectiveness is sparse. In Argentina, annual winter school breaks occur during the influenza season, providing an opportunity to study this intervention. We used 2005–2008 national weekly surveillance data of visits to a health care provider for influenza-like illness (ILI) from all provinces. Using Serfling-specified Poisson regressions and population-based census denominators, we developed incidence rate ratios (IRRs) for the 3 weeks before, 2 weeks during, and 3 weeks after the break. For persons 5–64 years of age, IRRs were <1 for at least 1 week after the break. Observed rates returned to expected by the third week after the break; overall decrease among persons of all ages was 14%. The largest decrease was among children 5–14 years of age during the week after the break (37% lower IRR). Among adults, effects were weaker and delayed. Two-week winter school breaks significantly decreased visits to a health care provider for ILI among school-aged children and nonelderly adults.
PMCID: PMC3713818  PMID: 23735682
Influenza; school closure; community mitigation; social isolation; Argentina; winter; viruses; respiratory infections
20.  Multiple Contact Dates and SARS Incubation Periods 
Emerging Infectious Diseases  2004;10(2):207-209.
Many severe acute respiratory syndrome (SARS) patients have multiple possible incubation periods due to multiple contact dates. Multiple contact dates cannot be used in standard statistical analytic techniques, however. I present a simple spreadsheet-based method that uses multiple contact dates to calculate the possible incubation periods of SARS.
PMCID: PMC3322923  PMID: 15030684
severe acute respiratory syndrome; incubation period; multiple contact dates; estimation; spreadsheet
21.  Influenza Pandemic Preparedness 
Emerging Infectious Diseases  2003;8(12):225-30.
PMCID: PMC3034335  PMID: 14725306
influenza; pandemic; preparedness; bioterrorism; resource allocation; priorities
22.  Risks and Benefits of Preexposure and Postexposure Smallpox Vaccination1 
Emerging Infectious Diseases  2003;9(11):1363-1370.
This article presents a model and decision criteria for evaluating a person’s risk of pre- or postexposure smallpox vaccination in light of serious vaccine-related adverse events (death, postvaccine encephalitis and progressive vaccinia). Even at a 1-in-10 risk of 1,000 initial smallpox cases, a person in a population of 280 million has a greater risk for serious vaccine-related adverse events than a risk for smallpox. For a healthcare worker to accept preexposure vaccination, the risk for contact with an infectious smallpox case-patient must be >1 in 100, and the probability of 1,000 initial cases must be >1 in 1,000. A member of an investigation team would accept preexposure vaccination if his or her anticipated risk of contact is 1 in 2.5 and the risk of attack is assumed to be >1 in 16,000. The only circumstances in which postexposure vaccination would not be accepted are the following: if vaccine efficacy were <1%, the risk of transmission were <1%, and (simultaneously) the risk for serious vaccine-related adverse events were >1 in 5,000.
PMCID: PMC3035543  PMID: 14718077
23.  Community-Based Values for 2009 Pandemic Influenza A H1N1 Illnesses and Vaccination-Related Adverse Events 
PLoS ONE  2011;6(12):e27777.
To evaluate community-based values for avoiding pandemic influenza (A) H1N1 (pH1N1) illness and vaccination-related adverse events in adults and children.
Adult community members were randomly selected from a nationally representative research panel to complete an internet survey (response rate = 65%; n = 718). Respondents answered a series of time trade-off questions to value four hypothetical health state scenarios for varying ages (1, 8, 35, or 70 years): uncomplicated pH1N1 illness, pH1N1 illness-related hospitalization, severe allergic reaction to the pH1N1 vaccine, and Guillain-Barré syndrome. We calculated descriptive statistics for time trade-off amounts and derived quality adjusted life year losses for these events. Multivariate regression analyses evaluated the effect of scenario age, as well as respondent socio-demographic and health characteristics on time trade-off amounts.
Respondents were willing to trade more time to avoid the more severe outcomes, hospitalization and Guillain-Barré syndrome. In our adjusted and unadjusted analyses, age of the patient in the scenario was significantly associated with time trade-off amounts (p-value<0.05), with respondents willing to trade more time to prevent outcomes in children versus adults. Persons who had received the pH1N1 vaccination were willing to trade significantly more time to avoid hospitalization, severe allergic reaction, and Guillain-Barré syndrome, controlling for other variables in adjusted analyses.(p-value<0.05)
Community members placed the highest value on preventing outcomes in children, compared with adults, and the time trade-off values reported were consistent with the severity of the outcomes presented. Considering these public values along with other decision-making factors may help policy makers improve the allocation of pandemic vaccine resources.
PMCID: PMC3242758  PMID: 22205927
24.  Cost-Effectiveness of 2009 Pandemic Influenza A(H1N1) Vaccination in the United States 
PLoS ONE  2011;6(7):e22308.
Pandemic influenza A(H1N1) (pH1N1) was first identified in North America in April 2009. Vaccination against pH1N1 commenced in the U.S. in October 2009 and continued through January 2010. The objective of this study was to evaluate the cost-effectiveness of pH1N1 vaccination.
A computer simulation model was developed to predict costs and health outcomes for a pH1N1 vaccination program using inactivated vaccine compared to no vaccination. Probabilities, costs and quality-of-life weights were derived from emerging primary data on pH1N1 infections in the US, published and unpublished data for seasonal and pH1N1 illnesses, supplemented by expert opinion. The modeled target population included hypothetical cohorts of persons aged 6 months and older stratified by age and risk. The analysis used a one-year time horizon for most endpoints but also includes longer-term costs and consequences of long-term sequelae deaths. A societal perspective was used. Indirect effects (i.e., herd effects) were not included in the primary analysis. The main endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted.
For vaccination initiated prior to the outbreak, pH1N1 vaccination was cost-saving for persons 6 months to 64 years under many assumptions. For those without high risk conditions, incremental cost-effectiveness ratios ranged from $8,000–$52,000/QALY depending on age and risk status. Results were sensitive to the number of vaccine doses needed, costs of vaccination, illness rates, and timing of vaccine delivery.
Vaccination for pH1N1 for children and working-age adults is cost-effective compared to other preventive health interventions under a wide range of scenarios. The economic evidence was consistent with target recommendations that were in place for pH1N1 vaccination. We also found that the delays in vaccine availability had a substantial impact on the cost-effectiveness of vaccination.
PMCID: PMC3146485  PMID: 21829456
25.  Health Economics of Dengue: A Systematic Literature Review and Expert Panel's Assessment 
Dengue vaccines are currently in development and policymakers need appropriate economic studies to determine their potential financial and public health impact. We searched five databases (PubMed, EMBASE, LILAC, EconLit, and WHOLIS) to identify health economics studies of dengue. Forty-three manuscripts were identified that provided primary data: 32 report economic burden of dengue and nine are comparative economic analyses assessing various interventions. The remaining two were a willingness-to-pay study and a policymaker survey. An expert panel reviewed the existing dengue economic literature and recommended future research to fill information gaps. Although dengue is an important vector-borne disease, the economic literature is relatively sparse and results have often been conflicting because of use of inconsistent assumptions. Health economic research specific to dengue is urgently needed to ensure informed decision making on the various options for controlling and preventing this disease.
PMCID: PMC3042827  PMID: 21363989

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