How do I facilitate a rapid response to a public health emergency requiring plasma collection with a public-private partnership?

In March 2020, there were no treatment options for COVID-19. Passive immune therapy including anti-SARS-CoV-2 hyperimmune globulin (hIVIG) was a logical candidate for COVID-19 therapeutic trials, given past success treating emerging pathogens with endogenous neutralizing antibodies. We established a plasma collection protocol for persons recovered from COVID-19. To speed recruitment in the first U.S. hotspot, Seattle, Washington, federal and state public health agencies collaborated with Bloodworks Northwest to collect convalescent plasma (CP) for manufacturing hIVIG. During March-December 2020, we identified and recruited prospective CP donors via letters to persons recovered from COVID-19 with laboratory-confirmed SARS-CoV-2 infection. Prospective donors were pre-screened and administered a medical history survey. Anti-SARS-CoV-2 neutralizing antibody (NAb) titers were classified as qualifying (≥1:80) or non-qualifying (<1:80) for enrollment based on a live virus neutralization assay. Generalized estimating equations were used to identify characteristics of donors associated with qualifying versus nonqualifying NAb titers. Overall, 21,359 letters resulted in 3207 inquiries, 2159 prescreenings with laboratory-confirmed SARS-CoV-2 infection, and 573 donors (27% of all pre-screenings with confirmed infection) who provided a screening plasma donation. Of 573 donors screened, 254 (44%) provided plasma with qualifying NAb titers, resulting in 1284 units for hIVIG manufacture. In a multivariable model, after adjusting for other factors, time (60 days) from COVID-19 symptom onset to screening was associated with lower odds of qualifying NAb (adjusted odds ratio = 0.67, 95% CI: 0.48-0.94). The collaboration facilitated a rapid response to develop and provide hIVIG for clinical trials and CP for transfusion. Only 1 in 12 donor inquiries resulted in a qualifying plasma donation. Challenges included recruitment and the relatively low percentage of persons with high NAb titers and limited screening capacity. This resource-intensive collaboration may not be scalable but informs preparedness and response strategies for plasma collection in future epidemics. Operational readiness plans with templates for screening, consent, and data collection forms are recommended.

Human Prion Disease Surveillance in Washington State, 2006-2017.

Importance: Human prion disease surveillance is critical to detect possible cases of variant Creutzfeldt-Jakob disease and other acquired forms of prion disease in the United States. Results are presented here that describe 12 years of surveillance in Washington, the only US state that has reported the presence of classic bovine spongiform encephalopathy, an animal prion disease that has been shown to transmit to humans. Objective: To describe the current prion disease surveillance system in Washington and the epidemiological and clinical results of surveillance from 2006 through 2017. Design, Setting, and Participants: This cross-sectional study reports findings from the human prion disease surveillance system in place in Washington state from January 1, 2006, through December 31, 2017. Participants included Washington residents with a clinical suspicion of human prion disease or suggestive test results from the National Prion Disease Pathology Surveillance Center or with prion disease listed as a cause of death on the death certificate. Data for this report were analyzed from June 1, 2016, to July 1, 2020. Exposure: Human prion disease diagnosis. Main Outcomes and Measures: The main outcome was incidence of human prion disease cases, including identification of variant Creutzfeldt-Jakob disease. Results: A total of 143 human prion disease cases were detected during the study period, none of which met criteria for a variant Creutzfeldt-Jakob disease diagnosis. Among 137 definite or probable cases, 123 (89.8%) occurred in persons aged 55 years or older, with a median age at death of 66 years (range, 38-84 years). Most patients were White (124 [92.5%] among 134 with reported race), and slightly over half were male (70 [51.1%]). The average annual age-adjusted prion disease incidence was 1.5 per million population per year, slightly higher than the national rate of 1.2 per million. A total of 99 cases (69.2%) were confirmed by neuropathology. Sporadic prion disease was the most common diagnosis, in 134 cases (93.7%), followed by familial prion disease in 8 cases (5.6%). One iatrogenic prion disease case (0.7%) was also reported. Conclusions and Relevance: The findings of this cross-sectional study suggest that demographic characteristics of patients with prion disease in Washington are consistent with national findings. The slightly higher incidence rate may be due to the state's enhanced surveillance activities, including close collaboration with key partners and educational efforts targeted toward health care providers. Results indicate that surveillance will continue to be beneficial for monitoring epidemiological trends, facilitating accurate diagnoses, and detecting variant Creutzfeldt-Jakob disease or other emerging human prion disease cases.

Effects of Air Pollution and Other Environmental Exposures on Estimates of Severe Influenza Illness, Washington, USA.

Ecologic models of influenza burden may be confounded by other exposures that share winter seasonality. We evaluated the effects of air pollution and other environmental exposures in ecologic models estimating influenza-associated hospitalizations. We linked hospitalization data, viral surveillance, and environmental data, including temperature, relative humidity, dew point, and fine particulate matter for 3 counties in Washington, USA, for 2001-2012. We used negative binomial regression models to estimate the incidence of influenza-associated respiratory and circulatory (RC) hospitalizations and to assess the effect of adjusting for environmental exposures on RC hospitalization estimates. The modeled overall incidence rate of influenza-associated RC hospitalizations was 31/100,000 person-years. The environmental parameters were statistically associated with RC hospitalizations but did not appreciably affect the event rate estimates. Modeled influenza-associated RC hospitalization rates were similar to published estimates, and inclusion of environmental covariates in the model did not have a clinically important effect on severe influenza estimates.

Opioid-Prescribing Metrics in Washington State: Trends and Challenges.

CONTEXT: Analyses of prescribing trends using prescription drug monitoring programs (PDMP) are impacted by changes in reporting requirements and in the scheduling of medications by the Drug Enforcement Administration. In 2014, the Drug Enforcement Administration changed the status of tramadol from an unscheduled to a scheduled medication. The addition of tramadol to the PDMP may affect the prevalence of opioid-prescribing metrics and the interpretation of prescribing trends. OBJECTIVE: The objectives were to (1) examine trends in opioid prescribing in Washington State between 2012 and 2017, (2) assess the potential impact of adding tramadol to PDMP on these trends, and (3) describe challenges in defining and implementing opioid-prescribing metrics. DESIGN: Analysis of quarterly summary statistics of opioid prescribing. SETTING: Washington State. PARTICIPANTS: Washington State residents. MAIN OUTCOME MEASURES: The metrics include measures of opioid prescribing overall and by age group, chronic opioid prescribing, high-dose prescribing among those on chronic opioid therapy, prescribing of concurrent opioids and sedatives, days' supply of new opioid prescriptions, and transition from short-term to long-term use of opioids. RESULTS: In Washington, the prevalence of any opioid prescribing, chronic opioid prescribing, high-dose opioid prescribing, and prescribing of concurrent opioids and sedatives declined between 2012 and 2017. The prevalence of opioid prescribing was higher in older than in younger age groups. The addition of tramadol to the Washington PDMP in 2014 affected the observed prevalence of all opioid metrics and of all opioid-prescribing trends. Conclusions about trends in opioid prescribing differ substantially depending on whether tramadol is included or not, particularly in 2014 and 2015. CONCLUSIONS: The development of opioid-prescribing metrics is relatively new. There is likely much benefit of standard definitions of opioid metrics at the state and national levels to track important trends and compare progress from state to state.

Surveillance of Opioid Prescribing as a Public Health Intervention: Washington State Bree Collaborative Opioid Metrics.

CONTEXT: To address risks associated with prescription opioid medications, guidelines recommend lower dose, shorter duration of use, and avoidance of concurrent sedatives. Monitoring opioid-prescribing practices is critical for assessing guideline impact, comparing populations, and targeting interventions to reduce risks. OBJECTIVE: To describe development of Washington (WA) State opioid-prescribing metrics, provide purpose and definitions, and apply metrics to prescription data for WA health care organizations. DESIGN: We describe the development and testing of opioid-prescribing metrics by the WA State Bree Collaborative opioid work group. SETTING: Washington State. PARTICIPANTS: Kaiser Permanente of Washington (KPW) Integrated Group Practice, KPW-contracted care providers, and WA Medicaid. MAIN OUTCOME MEASURES: Set of 6 strategic metrics tested across 3 different health systems adopted by WA State in 2017 for uniform tracking of opioid-prescribing guidelines and state policies. These metrics include (1) overall prevalence of any opioid use, (2) chronic use, (3) high-dose chronic use, (4) concurrent chronic sedative use, (5) days' supply of new prescriptions, and (6) transition from acute to chronic use. RESULTS: In the first quarter of 2010, 10% to 12% of KPW and 14% of Medicaid patients received at least 1 opioid prescription. Among opioid users, 22% to 24% of KPW and 36% of Medicaid patients received chronic opioids. Among patients receiving chronic opioids, 16% to 22% of KPW and 32% of Medicaid patients received high doses (≥90 morphine-equivalent dose per day) and 20% to 23% of KPW and 33% of Medicaid patients received concurrent chronic sedatives. Five percent of Medicaid and 2% to 3% of KPW patients receiving new opioid prescriptions transitioned to chronic opioid use. CONCLUSIONS: The metrics are relatively easy to calculate from electronic health care data and yield meaningful comparisons between populations or health plans. These metrics can be used to display trends over time and to evaluate the impact of opioid-prescribing policy interventions.

Outcomes of infants born to women with influenza A(H1N1)pdm09.

BACKGROUND: Pregnant women with influenza are more likely to have complications, but information on infant outcomes is limited. METHODS: Five state/local health departments collected data on outcomes of infants born to pregnant women with 2009 H1N1 influenza reported to the Centers for Disease Control and Prevention from April to December 2009. Collaborating sites linked information on pregnant women with confirmed 2009 H1N1 influenza, many who were severely ill, to their infants' birth certificates. Collaborators also collected birth certificate data from two comparison groups that were matched with H1N1-affected pregnancies on month of conception, sex, and county of residence. RESULTS: 490 pregnant women with influenza, 1,451 women without reported influenza with pregnancies in the same year, and 1,446 pregnant women without reported influenza with prior year pregnancies were included. Women with 2009 H1N1 influenza admitted to an intensive care unit (ICU; n = 64) were more likely to deliver preterm infants (<37 weeks), low birth weight infants, and infants with Apgar scores <=6 at 5 min than women in comparison groups (adjusted relative risk, aRR = 3.9 [2.7, 5.6], aRR = 4.6 [2.9, 7.5], and aRR = 8.7 [3.6, 21.2], for same year comparisons, respectively). Women with influenza who were not hospitalized and hospitalized women not admitted to the ICU did not have significantly elevated risks for adverse infant outcomes. CONCLUSIONS: Severely ill women with 2009 H1N1 influenza during pregnancy were more likely to have adverse birth outcomes than women without influenza, providing more support for influenza vaccination during pregnancy.

Use of Death Certificates to Identify Tuberculosis-Related Deaths in Washington State.

CONTEXT: Death certificates are routinely used to estimate tuberculosis (TB) mortality rates. The validity of International Classification of Diseases, Tenth Revision (ICD-10) codes and text cause of death data for this purpose is uncertain. OBJECTIVE: To evaluate the accuracy of ICD-10 coded and text cause of death data in identifying TB-related deaths in Washington State. DESIGN: Cross-sectional descriptive study comparing TB-related deaths detected through Washington State death certificates to TB-related deaths identified in the Washington State TB registry during 2009-2010. MAIN OUTCOME MEASURE(S): Sensitivity and positive predictive value of ICD-10 coded and text cause of death definitions in identifying TB-related deaths compared to the TB registry. RESULTS: All methods for identifying TB-related deaths using death certificate data overestimated the number of TB-related deaths compared to the tuberculosis registry. The positive predictive value ranged from 22% for a TB ICD-10 code as an underlying or multiple cause of death to 56% for TB listed in the direct cause of death text field. Seventeen (33%) of 51 subjects assigned with a TB ICD-10 code as an underlying or multiple cause of death had no evidence of TB on the death certificate and were not present in the TB registry. CONCLUSIONS: Death certificates were not highly predictive of TB-related deaths. Use of the direct cause of death text field was the most accurate method to identify a TB-related death when using death certificates. Specific ICD-10 coding algorithms may misclassify subjects as having died from TB.

Human Papillomavirus Vaccination in Washington State: Estimated Coverage and Missed Opportunities, 2006-2013.

OBJECTIVE: Human papillomavirus (HPV) causes almost all cervical cancer in women and contributes to vaginal, anal, oropharyngeal, and penile cancer morbidity and mortality. Although vaccines effective in preventing up to nine types of HPV are available, vaccination rates are low nationally. We assessed HPV vaccination coverage by age, sex, and county using Washington State Immunization Information System data. METHODS: We calculated on-time dose coverage by county and statewide among adolescents aged 11-12 years and assessed coverage by age 18 years. We calculated missed opportunities as the number of visits at which doses of other adolescent vaccines were administered without administration of the first dose of HPV vaccine (HPV1). RESULTS: In 2013, HPV vaccination coverage estimates with one, two, and three doses (HPV1-3) for adolescents aged 11-12 years were 48.5%, 32.4%, and 18.3% among girls and 31.2%, 17.1%, and 8.1% among boys. The three-dose HPV vaccine coverage estimate increased to 40.1% among girls by age 18 but was unchanged for boys. Coverage estimates varied by age, sex, and county. One-third of eligible unvaccinated girls and two of five eligible boys aged 11-17 years had at least one missed opportunity to receive HPV1. CONCLUSION: Despite a recommendation to vaccinate adolescents aged 11-12 years, HPV vaccination is often delayed and coverage levels among all age groups are below national target levels. Improved understanding of the variability of HPV vaccination coverage rates by age, sex, and county can inform targeted interventions statewide.

Use of Death Records to Augment Notifiable Conditions Reporting in Washington State.

CONTEXT: Health care providers are required to report newly diagnosed notifiable conditions including the case's vital status according to state regulations, but it is uncertain how many cases remain unreported. Death certificates could potentially serve as a data source for detecting unreported deaths due to notifiable conditions. OBJECTIVE: We sought to evaluate the usefulness of electronic death records to augment notifiable conditions reporting in Washington State. DESIGN: Cross-sectional study. SETTING: All residents of Washington State. PARTICIPANTS: Decedents from 2010-2012. MAIN OUTCOME MEASURES: Total number of fatal cases of acute infectious notifiable conditions in Washington residents estimated by capture-recapture analysis, proportion of estimated fatal cases reported to Washington's notifiable conditions database (Public Health Issue Management System [PHIMS]), and the proportion of estimated fatal cases identified solely from the death records. Information was obtained by searching multiple cause-of death fields on 2010-2012 death records for keywords for acute infectious notifiable conditions. RESULTS: Capture-recapture analysis estimated 317 fatal cases of these conditions could be expected over the 3 years studied (95% CI: 276,358). Public Health Issue Management System alone identified 38% of total estimated cases; using PHIMS and death record data increased identification to 71%. Electronic filing of death records was very timely, with a median of 4 days to visibility. Death record data were highly complete. CONCLUSIONS: Use of death records will augment the notifiable condition reporting system and potentially improve mortality estimates and disease control.

Laboratory practices and incidence of non-O157 shiga toxin-producing Escherichia coli infections.

We surveyed laboratories in Washington State, USA, and found that increased use of Shiga toxin assays correlated with increased reported incidence of non-O157 Shiga toxin-producing Escherichia coli (STEC) infections during 2005-2010. Despite increased assay use, only half of processed stool specimens underwent Shiga toxin testing during 2010, suggesting substantial underdetection of non-O157 STEC infections.

Age as an independent risk factor for intensive care unit admission or death due to 2009 pandemic influenza A (H1N1) virus infection.

OBJECTIVE: This study evaluated risk factors for intensive care unit (ICU) admission or death among people hospitalized with 2009 pandemic influenza A (pH1N1) virus infection. METHODS: We based analyses on data collected in Washington State from April 27 to September 18, 2009, on deceased or hospitalized people with laboratory-confirmed pH1N1 infection reported by health-care providers and hospitals as part of enhanced public health surveillance. We used bivariate analyses and multivariable logistic regression to identify risk factors associated with ICU admission or death due to pH1N1. RESULTS: We identified 123 patients admitted to the hospital but not an ICU and 61 patients who were admitted to an ICU or died. Independent of high-risk medical conditions, both older age and delayed time to hospital admission were identified as risk factors for ICU admission or death due to pH1N1. Specifically, the odds of ICU admission or death were 4.44 times greater among adults aged 18-49 years (95% confidence interval [CI] 1.97, 10.02) and 5.93 times greater among adults aged 50-64 years (95% CI 2.24, 15.65) compared with pediatric patients < 18 years of age. Likewise, hospitalized cases admitted more than two days after illness onset had 2.17 times higher odds of ICU admission or death than those admitted within two days of illness onset (95% CI 1.10, 4.25). CONCLUSION: Although certain medical conditions clearly influence the need for hospitalization among people infected with pH1N1 virus, older age and delayed time to admission each played an independent role in the progression to ICU admission or death among hospitalized patients.

H275Y mutant pandemic (H1N1) 2009 virus in immunocompromised patients.

Most oseltamivir-resistant pandemic (H1N1) 2009 viruses have been isolated from immunocompromised patients. To describe the clinical features, treatment, outcomes, and virologic data associated with infection from pandemic (H1N1) 2009 virus with H275Y mutation in immunocompromised patients, we retrospectively identified 49 hematology-oncology patients infected with pandemic (H1N1) 2009 virus. Samples from 33 of those patients were tested for H275Y genotype by allele-specific real-time PCR. Of the 8 patients in whom H275Y mutations was identified, 1 had severe pneumonia; 3 had mild pneumonia with prolonged virus shedding; and 4 had upper respiratory tract infection, of whom 3 had prolonged virus shedding. All patients had received oseltamivir before the H275Y mutation was detected; 1 had received antiviral prophylaxis. Three patients excreted resistant virus for >60 days. Emergence of oseltamivir resistance is frequent in immunocompromised patients infected with pandemic (H1N1) 2009 virus and can be associated with a wide range of clinical disease and viral kinetics.

Epidemiology of 2009 pandemic influenza A (H1N1) deaths in the United States, April-July 2009.

During the spring of 2009, pandemic influenza A (H1N1) virus (pH1N1) was recognized and rapidly spread worldwide. To describe the geographic distribution and patient characteristics of pH1N1-associated deaths in the United States, the Centers for Disease Control and Prevention requested information from health departments on all laboratory-confirmed pH1N1 deaths reported from 17 April through 23 July 2009. Data were collected using medical charts, medical examiner reports, and death certificates. A total of 377 pH1N1-associated deaths were identified, for a mortality rate of .12 deaths per 100,000 population. Activity was geographically localized, with the highest mortality rates in Hawaii, New York, and Utah. Seventy-six percent of deaths occurred in persons aged 18-65 years, and 9% occurred in persons aged ≥ 65 years. Underlying medical conditions were reported for 78% of deaths: chronic lung disease among adults (39%) and neurologic disease among children (54%). Overall mortality associated with pH1N1 was low; however, the majority of deaths occurred in persons aged <65 years with underlying medical conditions.

Hospitalized patients with 2009 pandemic influenza A (H1N1) virus infection in the United States--September-October 2009.

Given the potential worsening clinical severity of 2009 pandemic influenza A (H1N1) virus (pH1N1) infection from spring to fall 2009, we conducted a clinical case series among patients hospitalized with pH1N1 infection from September through October 2009. A case patient was defined as a hospitalized person who had test results positive for pH1N1 virus by real-time reverse-transcription polymerase chain reaction. Among 255 hospitalized patients, 34% were admitted to an intensive care unit and 8% died. Thirty-four percent of patients were children <18 years of age, 8% were adults ≥ 65 years of age, and 67% had an underlying medical condition. Chest radiographs obtained at hospital admission that had findings that were consistent with pneumonia were noted in 103 (46%) of 255 patients. Among 255 hospitalized patients, 208 (82%) received neuraminidase inhibitors, but only 47% had treatment started ≤ 2 days after illness onset. Overall, characteristics of hospitalized patients with pH1N1 infection in fall 2009 were similar to characteristics of patients hospitalized with pH1N1 infection in spring 2009, which suggests that clinical severity did not change substantially over this period.

Chlamydial infections among female adolescents screened in juvenile detention centers in Washington State, 1998-2002.

OBJECTIVE: The objective of this study was to assess trends in Chlamydia trachomatis positivity and associated risk factors among detained female adolescents. GOAL: The goal of this study was to determine trends in prevalence of chlamydia among detained female adolescents. STUDY DESIGN: We retrospectively reviewed risk factor data and chlamydia results collected by providers during 1998-2002 at four large juvenile detention centers in Washington State that routinely screen female adolescents for C. trachomatis. RESULTS: Of 3,593 tests, a total of 493 (13.7%) were positive for chlamydia. High chlamydia positivity was sustained throughout the 5-year period (range, 12.5-15.0%) with no statistically significant trends in positivity. Independent risk factors for chlamydial infection included report of more than one sex partner in the previous 60 days (adjusted odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.19-2.04) and previous chlamydial infection within 12 months (adjusted OR = 1.87, 95% CI = 1.45-2.40). CONCLUSIONS: Efforts are needed to promote chlamydia screening programs in juvenile detention centers because these sites have access to high-risk sexually active female adolescents.

Babesia divergens-like infection, Washington State.

Most reported U.S. zoonotic cases of babesiosis have occurred in the Northeast and been caused by Babesia microti. In Washington State, three cases of babesiosis have been reported previously, which were caused by WA1 (for "Washington 1")-type parasites. We investigated a case of babesiosis in Washington in an 82-year-old man whose spleen had been removed and whose parasitemia level was 41.4%. The complete 18S ribosomal RNA gene of the parasite was amplified from specimens of his whole blood by polymerase chain reaction. Phylogenetic analysis showed the parasite is most closely related, but not identical, to B. divergens (similarity score, 99.5%), a bovine parasite in Europe. By indirect fluorescent-antibody testing, his serum reacted to B. divergens but not to B. microti or WA1 antigens. This case demonstrates that babesiosis can be caused by novel parasites detectable by manual examination of blood smears but not by serologic or molecular testing for B. microti or WA1-type parasites.

Expanded geographical distribution of the N family of Mycobacterium tuberculosis strains within the United States.

The N and W-Beijing families of Mycobacterium tuberculosis are phylogenetically closely related. The ability of the W-Beijing family to rapidly cause widespread disease is well described; however, few outbreaks involving the N family have been reported outside the New York City, N.Y., area. During 2002 to 2003, Seattle, Wash., experienced a rapidly expanding tuberculosis outbreak involving 38 persons in a 23-month period. The outbreak strain, SBRI9, exhibited the genotypic properties of the N family. Its IS6110 restriction fragment length polymorphism pattern was identical or nearly identical to those of two N family strains that were responsible for clusters of tuberculosis cases, including a large nosocomial outbreak, in New York City and New Jersey from 1989 to 1990. It was also identical to strains involved in late 1990s tuberculosis cases in Michigan, Maryland, and Arkansas. Further monitoring of the N family may show that it shares with the W-Beijing family the propensity to spread rapidly, suggesting that this characteristic evolved prior to the divergence of the two genetic lineages.