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BackgroundUptake of COVID-19 bivalent vaccines and oral medication nirmatrelvir-ritonavir (Paxlovid) has remained low across the United States. Assessing the public health impact of increasing uptake of these interventions in key risk groups can guide further public health resources and policy.MethodsThis modeling study used person-level data from the California Department of Public Health on COVID-19 cases, hospitalizations, deaths, and vaccine administration from July 23, 2022 to January 23, 2023. We modeled the impact of additional uptake of bivalent COVID-19 vaccines and nirmatrelvir-ritonavir during acute illness in different risk groups defined by age (50+, 65+, 75+ years) and vaccination status (everyone, primary series only, previously vaccinated). We predicted the number of averted COVID-19 cases, hospitalizations, and deaths and number needed to treat (NNT).ResultsFor both bivalent vaccines and nirmatrelvir-ritonavir, the most efficient strategy (based on NNT) for averting severe COVID-19 was targeting the 75+ years group. We predicted that perfect coverage of bivalent boosters in the 75+ years group would avert 3,920 hospitalizations (95%UI: 2,491-4,882; 7.8% total averted; NNT 387) and 1,074 deaths (95%UI: 774-1,355; 16.2% total averted; NNT 1,410). Perfect uptake of nirmatrelvir-ritonavir in the 75+ years group would avert 5,644 hospitalizations (95%UI: 3,947-6,826; 11.2% total averted; NNT 11) and 1,669 deaths (95%UI: 1,053-2,038; 25.2% total averted; NNT 35).ConclusionsThese findings suggest prioritizing uptake of bivalent boosters and nirmatrelvir-ritonavir among the oldest age groups would be efficient and have substantial public health impact in reducing the burden of severe COVID-19, but would not address the entire burden of severe COVID-19.

Despite widespread vaccination against COVID-19 in the United States, there are limited empirical data quantifying their public health impact in the population.To estimate the number of COVID-19 cases, hospitalizations, and deaths directly averted because of COVID-19 vaccination in California.This modeling study used person-level data provided by the California Department of Public Health (CDPH) on COVID-19 cases, hospitalizations, and deaths as well as COVID-19 vaccine administration from January 1, 2020, to October 16, 2021. A statistical model was used to estimate the number of COVID-19 cases that would have occurred in the vaccine era (November 29, 2020, to October 16, 2021) in the absence of vaccination based on the ratio of the number of cases among the unvaccinated (aged12 years) and vaccine-eligible groups (aged ≥12 years) before vaccine introduction. Vaccine-averted COVID-19 cases were estimated by finding the difference between the projected and observed number of COVID-19 cases. Averted COVID-19 hospitalizations and deaths were assessed by applying estimated hospitalization and case fatality risks to estimates of vaccine-averted COVID-19 cases. As a sensitivity analysis, a second independent model was developed to estimate the number of vaccine-averted COVID-19 outcomes by applying published data on vaccine effectiveness to data on COVID-19 vaccine administration and estimated risk of COVID-19 over time.COVID-19 vaccination.Number of COVID-19 cases, hospitalizations, and deaths estimated to have been averted because of COVID-19 vaccination.There were 4 585 248 confirmed COVID-19 cases, 240 718 hospitalizations, and 70 406 deaths in California from January 1, 2020, to October 16, 2021, during which 27 164 680 vaccine-eligible individuals aged 12 years and older were reported to have received at least 1 dose of a COVID-19 vaccine in the vaccine era (79.5% of the eligible population). The primary model estimated that COVID-19 vaccination averted 1 523 500 (95% prediction interval [PI], 976 800-2 230 800) COVID-19 cases in California, corresponding to a 72% (95% PI, 53%-91%) relative reduction in cases because of vaccination. COVID-19 vaccination was estimated to have averted 72 930 (95% PI, 53 250-99 160) hospitalizations and 19 430 (95% PI, 14 840-26 230) deaths during the study period. The alternative model identified comparable findings.This study provides evidence of the public health benefit of COVID-19 vaccination in the United States and further supports the urgency for continued vaccination.

Background: For countries that have only recently started COVID-19 vaccinations, there remains a key public health question of who should be prioritized for early vaccination. Most vaccine prioritization analyses have only considered variation in risk of infection and death by age. We provide a more granular analysis with stratification by demographics, risk factors, and location. Methods: We used a simulation model to compare the impact of different prioritization strategies on COVID-19 cases, deaths and disability-adjusted life years (DALYs) over the first 6 months of vaccine rollout. We calibrated the model to demographic and location data on 28,175 COVID-19 deaths in California up to December 30, 2020, and incorporated variation in risk by occupation and comorbidity status using published estimates. We estimated the proportion of clinical cases, deaths and DALYs averted relative to a scenario of no vaccination for strategies prioritizing vaccination by a single risk factor (special population status (e.g. incarcerated individual), age, essential worker status, comorbidity status) or multiple risk factors (e.g. age and location). Results: We found that age-based targeting averted the most deaths (65% for 5 million individuals vaccinated) and DALYs (40%) of strategies targeting by a single risk factor and targeting essential workers averted the least deaths (33%) and DALYs (25%) over the first 6 months of vaccine rollout. However, targeting by two or more risk factors simultaneously averted up to 40% more DALYs. Conclusions: Our findings highlight the potential value of multiple-risk-factor targeting of COVID-19 vaccination. Where vaccine supply is limited and logistical challenges in vaccine delivery persist, age-based targeting offers a means of ensuring that vaccines reach those most at risk of poor health outcomes. If operational challenges can be overcome, more granular vaccination strategies that overlap age with other risk factors can be adopted.

A critical question in the COVID-19 pandemic is how to optimally allocate the first available vaccinations to maximize health impact. We used a static simulation model with detailed demographic and risk factor stratification to compare the impact of different vaccine prioritization strategies in the United States on key health outcomes, using California as a case example. We calibrated the model to demographic and location data on 28,175 COVID-19 deaths in California up to December 30, 2020, and incorporated variation in risk by occupation and comorbidity status using published estimates. We predicted the proportion of COVID-19 clinical cases, deaths and disability-adjusted life years (DALYs) averted over 6 months relative to a scenario of no vaccination for five vaccination strategies that prioritized vaccination by a single risk factor: random allocation; targeting special populations (e.g. incarcerated individuals); targeting older individuals; targeting essential workers; and targeting individuals with comorbidities. Targeting older individuals averted the highest proportion of DALYs (40% for 5 million individuals vaccinated) and deaths (65%) but the lowest proportion of cases (12%). Targeting essential workers averted the lowest proportion of DALYs (25%) and deaths (33%). Allocating vaccinations simultaneously by age and location or by age, sex, race/ethnicity, location, occupation, and comorbidity status averted a significantly higher proportion of DALYs (48% and 56%) than any strategy prioritizing by a single risk factor. Our results corroborate findings of other studies that age targeting is the best single-risk-factor prioritization strategy for averting DALYs, and suggest that targeting by multiple risk factors would provide additional benefit. Significance statement COVID-19 has caused a global pandemic, and a key public health question is who should get the first available vaccinations. Most vaccine prioritization analyses have only considered variation in risk of infection and death by age and occupation. We provide a more granular analysis with stratification by demographics, risk factors, and location. We predict the impact of different prioritization strategies on COVID-19 cases, deaths and disability-adjusted life years (DALYs). We find that age-based targeting averts the most deaths and DALYs of strategies targeting by a single risk factor, but that targeting by two or more risk factors simultaneously would avert significantly more deaths and DALYs. Our findings highlight the potential value of multiple-risk-factor targeting of vaccination when supply is limited.

While the subject of translating poems for adults between modern languages is a common field of study worldwide, critical study of the artistic methods and challenges of translating poems for children remains rare across popular and academic literatures. This essay examines multiple approaches to translating “Circus Elephant,” a short imagist poem in English written by Steven Withrow. Versions of the poem in Spanish, Greek, Afrikaans, French, and Italian are included, along with the translators’ notes about choices of diction, sound, structure, and denotative and connotative meaning. The author also explores the idea that composing a translation that moves beyond a hastily constructed, wordfor-word trot is a creative act, an artistic form in itself. Honoring the spirit of the poem requires a patient, painstaking, sensitive, imaginative translator who thinks and acts as a poet. A good translation balances craft and inspiration.

The almost universal administration of childhood immunisations has been associated with logarithmic drops in the incidence of a number of diseases in the United States and worldwide. In the United States, mandatory school immunisation laws have in particular been instrumental in achieving the high levels of coverage needed to sustain herd immunity. However, concerns about vaccine safety led to the passing of the National Childhood Vaccine Injury Act of 1986, which uses a no-fault system compensation system for people found to be injured by certain vaccines. The measles vaccine is highly effective, and outbreaks of measles are usually the consequence of failure to vaccinate. A high-profile outbreak of measles at a southern California amusement park in 2014 led the state of California to further restrict the ability of children to attend school if they are not immunized because of their family’s beliefs. Immunisation requirements are but one of many legal mandates designed for public health protection, from mandatory fluoridation of drinking water to quarantine and isolation for communicable diseases. We conclude that school immunisation requirements help governments fulfil their duty to protect and promote public health., Gotovo univerzalna imunizacija djece povezana je s logaritamskim opadanjem broja zaraza kako u Sjedinjenim Državama tako i svijetu. U Sjedinjenim Državama, zakon o obveznom cijepljenju školske djece pokazao se posebno korisnim za postizanje visokog stupnja zaštite potrebne za održavanje imunosti zajednice. Međutim, zabrinutosti oko sigurnosti cjepiva dovele su do donošenja National Childhood Vaccine Injury Act (Nacionalni zakon o štetnosti dječjeg cjepiva) iz 1986., prema kojem se kroz „no-fault sustav“ (bez obzira tko je kriv) kompenziraju oštećeni određenim cjepivima. Cjepivo protiv ospica iznimno je učinkovito, a pojave ospica najčešće su povezane s neprimanjem cjepiva. Zbog poznatog slučaja pojave ospica u kalifornijskom zabavnom parku 2014., savezna država Kalifornija dodatno je ograničila mogućnost pohađanja škole djece koja nisu cijepljena zbog obiteljskih uvjerenja. Obvezno cijepljenje predstavlja samo jednu od odredbi kojima je cilj zaštita javnog zdravlja, a ,eđu kojima su i obvezna fluoridacija pitke vode i karantena i izolacija zbog prenosivih bolesti. Zaključujemo da obvezno cijepljenje školske djece pomaže vladama u ispunjenju njihove dužnosti u zaštiti i unaprjeđenju javnog zdravstva., Eine fast universelle Immunisierung der Kinder ist, sowie in den USA als auch in der übrigen Welt, mit einer logarithmischen Abnahme der Ansteckungsfälle verbunden. In den USA hat sich das Gesetz über die Pflichtimpfung von Schulkindern als besonders nützlich zum Erreichen einer hohen Stufe des für Erhalten der Immunität der Gemeinschaft nötigen Schutzes erwiesen. Allerdings haben die Bedenken über die Impfsicherheit zum Erlassen des Nationalen Kindheits-Impfstoff-Verletzungsgesetz aus dem Jahr 1986 (National Childhood Vaccine Injury Act) geführt, wonach durch ein „No-Fault-System“ (ungeachtet dessen, wer die Schuld trägt) die durch bestimmte Impfstoffe Betroffenen entschädigt werden. Der Masernimpfstoff ist außerordentlich effizient und die Masernfälle sind meistens mit der Nichtimpfung verbunden. Wegen des bekannten Falls des Masernausbruchs im kalifornischen Vergnügungspark 2014 hat der Bundesstaat Kalifornien zusätzlich den Schulbesuch von Kindern beschränkt, die aus Familienüberzeugung nicht geimpft wurden. Die Pflichtimpfung ist nur eine von Bestimmungen, deren Ziel der Schutz der öffentlichen Gesundheit ist, dazu gehören noch die obligatorische Trinkwasserfluoridierung, Quarantäne und und Isolation wegen übertragbaren Krankheiten. Wir kommen zum Schluß, dass die Pflichtimpfung von Schulkindern den Regierungen hilft, ihre Pflichten im Rahmen des Schutzes und der Förderung der öffentlichen Gesundheit zu erfüllen.

Background Neuraminidase inhibitor (NAI) antiviral drugs can shorten the duration of uncomplicated influenza when administered early ( Methods We analyzed California surveillance data to characterize the outcomes of patients in intensive care units (ICUs) treated with NAIs for influenza A(H1N1)pdm09 (pH1N1). Demographic and clinical data were abstracted from medical records, using standardized case report forms. Results From 3 April 2009 through 10 August 2010, 1950 pH1N1 cases hospitalized in ICUs were reported. Of 1859 (95%) with information available, 1676 (90%) received NAI treatment, and 183 (10%) did not. The median age was 37 years (range, 1 week-93 years), 1473 (79%) had ≥1 comorbidity, and 492 (26%) died. The median time from symptom onset to starting NAI treatment was 4 days (range, 0-52 days). NAI treatment was associated with survival: 107 of 183 untreated case patients (58%) survived, compared with 1260 of 1676 treated case patients (75%; P ≤ .0001). There was a trend toward improved survival for those treated earliest (P Conclusions NAI treatment of critically ill pH1N1 patients improves survival. While earlier treatment conveyed the most benefit, patients who started treatment up to 5 days after symptom onset also were more likely to survive. Further research is needed about whether starting NAI treatment >5 days after symptom onset may also convey benefit.

Background many critically ill patients with 2009 pandemic influenza A (H1N1) (2009 H1N1) infection were noted to be obese, but whether obesity, rather than its associated co-morbidities, is an independent risk factor for severe infection is unknown. Methods using public health surveillance data, we analyzed demographic and clinical characteristics of California residents hospitalized with 2009 H1N1 infection to assess whether obesity (body mass index [BMI] ≥ 30) and extreme obesity (BMI ≥ 40) were an independent risk factor for death among case patients ≥ 20 years old. Results during the period 20 April-11 August 2009, 534 adult case patients with 2009 H1N1 infection for whom BMI information was available were observed. Two hundred twenty-eight patients (43%) were ≥ 50 years of age, and 378 (72%) had influenza-related high-risk conditions recognized by the Advisory Committee on Immunization Practices as risk factors for severe influenza. Two hundred and seventy-four (51%) had BMI ≥ 30, which is 2.2 times the prevalence of obesity among California adults (23%) and 1.5 times the prevalence among the general population of the United States (33%). Of the 92 case patients who died (17%), 56 (61%) had BMI ≥ 30 and 28 (30%) had BMI ≥ 40. In multivariate analysis, BMI ≥ 40 (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.4-5.9) and BMI ≥ 45 (OR, 4.2; 95% CI, 1.9-9.4), age ≥ 50 years (OR, 2.1; 95% CI, 1.2-3.7), miscellaneous immunosuppressive conditions (OR, 3.9; 95% CI, 1.6-9.5), and asthma (OR, 0.5; 95% CI, 0.3-0.9) were associated with death. Conclusion half of Californians ≥ 20 years of age hospitalized with 2009 H1N1 infection were obese. Extreme obesity was associated with increased odds of death. Obese adults with 2009 H1N1 infection should be treated promptly and considered in prioritization of vaccine and antiviral medications during shortages.

Background Influenza surveillance is valuable for monitoring trends in influenza-related morbidity and mortality. Using the 2005–2006 influenza season as an example, this paper describes a comprehensive influenza surveillance program used by the California Department of Public Health (CDPH). Methods Data collected from patients evaluated for acute respiratory illness in a given week were reported and summarized the following week, including (1) electronic hospital pneumonia and influenza admission and antiviral usage records from Kaiser Permanente, (2) sentinel provider influenza-like illness (ILI) reports, (3) severe pediatric influenza case reports (e.g., children either hospitalized in intensive care or expired), (4) school clinic ILI evaluations, and (5) positive influenza test results from a network of academic, hospital, commercial, and public health laboratories and the state CDPH Viral and Rickettsial Disease Laboratory. Results Influenza activity in California in the 2005–2006 season was moderate in severity; all clinical and laboratory markers rose and fell consistently. Extensive laboratory characterization identified the predominant circulating virus strain as A/California/7/2004(H3N2), which was a component of the 2005–2006 influenza vaccine; 96% of samples tested showed adamantane resistance. Conclusions By using multiple, complementary surveillance methods coupled with a strong laboratory component, the CDPH has developed a simple, flexible, stable, and widely accepted influenza surveillance system that can monitor trends in statewide influenza activity, ascertain the correlation between circulating strains with vaccine strains, and assist with detection of new strain variants. The methods described can serve as a model for influenza surveillance in other states.

We created the orphan drug Human Botulism Immune Globulin Intravenous (Human) (BIG-IV), which neutralizes botulinum toxin, and evaluated its safety and efficacy in treating infant botulism, the intestinal-toxemia form of human botulism.We performed a five-year, randomized, double-blind, placebo-controlled trial statewide, in California, of BIG-IV in 122 infants with suspected (and subsequently laboratory-confirmed) infant botulism (75 caused by type A Clostridium botulinum toxin, and 47 by type B toxin); treatment was given within three days after hospital admission. We subsequently performed a 6-year nationwide, open-label study of 382 laboratory-confirmed cases of infant botulism treated within 18 days after hospital admission.As compared with the control group in the randomized trial, infants treated with BIG-IV had a reduction in the mean length of the hospital stay, the primary efficacy outcome measure, from 5.7 weeks to 2.6 weeks (P0.001). BIG-IV treatment also reduced the mean duration of intensive care by 3.2 weeks (P0.001), the mean duration of mechanical ventilation by 2.6 weeks (P=0.01), the mean duration of tube or intravenous feeding by 6.4 weeks (P0.001), and the mean hospital charges per patient by 88,600 dollars (in 2004 U.S. dollars; P0.001). There were no serious adverse events attributable to BIG-IV. In the open-label study, infants treated with BIG-IV within seven days of admission had a mean length of hospital stay of 2.2 weeks, and early treatment with BIG-IV shortened the mean length of stay significantly more than did later treatment.Prompt treatment of infant botulism type A or type B with BIG-IV was safe and effective in shortening the length and cost of the hospital stay and the severity of illness.

We compared the QuickVue Influenza test with PCR for diagnosing pandemic (H1N1) 2009 in 404 persons with influenza-like illness. Overall sensitivity, specificity, and positive and negative predictive values were 66%, 84%, 84%, and 64%, respectively. Rapid test results should be interpreted cautiously when pandemic (H1N1) 2009 virus is suspected.

OBJECTIVE: Timely treatment with neuraminidase inhibitor (NAI) drugs appears to improve survival in adults hospitalized with influenza. We analyzed California surveillance data to determine whether NAI treatment improves survival in critically ill children with influenza. METHODS: We analyzed data abstracted from medical records to characterize the outcomes of patients aged 0 to 17 years hospitalized in ICUs with laboratory-confirmed influenza from April 3, 2009, through September 30, 2012. RESULTS: Seven hundred eighty-four influenza cases aged CONCLUSIONS: Prompt treatment with NAIs may improve survival of children critically ill with influenza. Recent decreased frequency of NAI treatment of influenza may be placing untreated critically ill children at an increased risk of death.

BACKGROUND The 2009 H1N1 influenza virus emerged in April 2009 and primarily affected children and young adults. Few reports describe 2009 H1N1 influenza infection in infants. This report describes the clinical and epidemiologic features of 2009 H1N1 influenza in critically ill infants younger than 1 year of age. METHODS Laboratory-confirmed cases were reported to the California Department of Public Health as part of public health surveillance for 2009 H1N1 influenza. Data were collected using standardized report forms and medical-chart abstractions. RESULTS From April 23, 2009 through May 1, 2010, 82 cases of infants hospitalized in the intensive care unit with 2009 H1N1 influenza were reported in California. Medical charts were available for 77 of the infants, whose median age was 109 days (range: 1-361 days). Twenty-seven (35%) infants had a gestational age of 36 weeks or less. More than half (46; 60%) of the infants had at least 1 reported chronic medical condition. Thirty-five (45%) infants required mechanical ventilation; 7 (9%) died. Five infants were hospitalized since birth and acquired influenza infection during their admission; 2 (40%) of these infants died. CONCLUSIONS Infants who are premature or with chronic conditions seem to be at increased risk for developing severe 2009 H1N1 influenza infection. We encourage clinicians to maintain high suspicion for influenza in infants when influenza viruses are circulating. Vaccination should be encouraged among contacts of infants

Objective In 2010, California experienced the highest number of pertussis cases in >60 years, with >9000 cases, 809 hospitalizations, and 10 deaths. This report provides a descriptive epidemiologic analysis of this epidemic and describes public health mitigation strategies that were used, including expanded pertussis vaccine recommendations. Study design Clinical and demographic information were evaluated for all pertussis cases with onset from January 1, 2010, through December 31, 2010, and reported to the California Department of Public Health. Results Hispanic infants younger than 6 months had the highest disease rates; all deaths and most hospitalizations occurred in infants younger than 3 months. Most pediatric cases were vaccinated according to national recommendations, although 9% of those aged 6 months to 18 years were completely unvaccinated against pertussis. High disease rates also were observed in fully vaccinated preadolescents, especially 10-year-olds. Mitigation strategies included expanded tetanus, diphtheria, and acellular pertussis vaccine recommendations, public and provider education, distribution of free vaccine for postpartum women and contacts of infants, and clinical guidance on diagnosis and treatment of pertussis in young infants. Conclusions Infants too young to be fully vaccinated against pertussis remain at highest risk of severe disease and death. Data are needed to evaluate strategies offering direct protection of this vulnerable population, such as immunization of pregnant women and of newborns. The high rate of disease among preadolescents suggests waning of immunity from the diphtheria, tetanus, and acellular pertussis series; additional studies are warranted to evaluate the efficacy and duration of protection of the diphtheria, tetanus, and acellular pertussis series and the tetanus, diphtheria, and acellular pertussis series.

Background While children and young adults had the highest attack rates due to 2009 pandemic (H1N1) influenza A (2009 H1N1), studies of hospitalized cases noted high fatality in older adults. We analyzed California public health surveillance data to better characterize the populations at risk for dying due to 2009 H1N1. Methods and Findings A case was an adult ≥20 years who died with influenza-like symptoms and laboratory results indicative of 2009 H1N1. Demographic and clinical data were abstracted from medical records using a standardized case report form. From April 3, 2009 – August 10, 2010, 541 fatal cases ≥20 years with 2009 H1N1 were reported. Influenza fatality rates per 100,000 population were highest in persons 50–59 years (3.5; annualized rate = 2.6) and 60–69 years (2.3; annualized rate = 1.7) compared to younger and older age groups (0.4–1.9; annualized rates = 0.3–1.4). Of 486 cases hospitalized prior to death, 441 (91%) required intensive care unit (ICU) admission. ICU admission rates per 100,000 population were highest in adults 50–59 years (8.6). ICU case-fatality ratios among adults ranged from 24–42%, with the highest ratios in persons 70–79 years. A total of 425 (80%) cases had co-morbid conditions associated with severe seasonal influenza. The prevalence of most co-morbid conditions increased with increasing age, but obesity, pregnancy and obstructive sleep apnea decreased with age. Rapid testing was positive in 97 (35%) of 276 tested. Of 482 cases with available data, 384 (80%) received antiviral treatment, including 49 (15%) of 328 within 48 hours of symptom onset. Conclusions Adults aged 50–59 years had the highest fatality due to 2009 H1N1; older adults may have been spared due to pre-existing immunity. However, once infected and hospitalized in intensive care, case-fatality ratios were high for all adults, especially in those over 60 years. Vaccination of adults older than 50 years should be encouraged.

Influenza surveillance is valuable for monitoring trends in influenza-related morbidity and mortality. Using the 2005-2006 influenza season as an example, this paper describes a comprehensive influenza surveillance program used by the California Department of Public Health (CDPH).Data collected from patients evaluated for acute respiratory illness in a given week were reported and summarized the following week, including (1) electronic hospital pneumonia and influenza admission and antiviral usage records from Kaiser Permanente, (2) sentinel provider influenza-like illness (ILI) reports, (3) severe pediatric influenza case reports (e.g., children either hospitalized in intensive care or expired), (4) school clinic ILI evaluations, and (5) positive influenza test results from a network of academic, hospital, commercial, and public health laboratories and the state CDPH Viral and Rickettsial Disease Laboratory.Influenza activity in California in the 2005-2006 season was moderate in severity; all clinical and laboratory markers rose and fell consistently. Extensive laboratory characterization identified the predominant circulating virus strain as A/California/7/2004(H3N2), which was a component of the 2005-2006 influenza vaccine; 96% of samples tested showed adamantane resistance.By using multiple, complementary surveillance methods coupled with a strong laboratory component, the CDPH has developed a simple, flexible, stable, and widely accepted influenza surveillance system that can monitor trends in statewide influenza activity, ascertain the correlation between circulating strains with vaccine strains, and assist with detection of new strain variants. The methods described can serve as a model for influenza surveillance in other states.

OBJECTIVE. The 2003–2004 influenza season was marked by both the emergence of a new drift “Fujian” strain of influenza A virus and prominent reports of increased influenza-related deaths in children in the absence of baseline data for comparison. In December 2003, the California Department of Health Services initiated surveillance of children who were hospitalized in California with severe influenza in an attempt to measure its impact and to identify additional preventive measures. METHODS. From December 2003 to May 2005, surveillance of children who were hospitalized in PICUs or dying in the hospital with laboratory evidence of influenza was performed by hospital infection control practitioners and local public health departments using a standardized case definition and reporting form. RESULTS. In the 2003–2004 and 2004–2005 influenza seasons, 125 and 35 cases, respectively, of severe influenza in children were identified in California. The mean and median age of cases were 3.1 years and 1.5 years, with breakdown as follows: CONCLUSIONS. More than 3 times as many children were reported to be hospitalized in intensive care with influenza in California during the 2003–2004 season compared with the 2004–2005 season. Because children who are younger than 6 months remain at highest risk for severe influenza yet cannot currently be immunized, development and validation of preventive measures for them (eg, maternal immunization, breastfeeding, immunization of young infants and their close contacts) are urgently needed. ACIP's recent recommendation for influenza vaccination of children with conditions that can compromise respiratory function (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, other neuromuscular disorders) is further supported by the frequency of underlying neurologic disease in these cases of severe influenza. A significant proportion of children with severe influenza in California, including children who are aged 2 to 4 years or have underlying genetic syndromes or prematurity, would not have been routinely recommended for influenza vaccination in 2005–2006 ACIP and AAP recommendations, calling into question whether such guidelines should be expanded. Continued surveillance for severe influenza-related morbidity and mortality is important to measure the impact of influenza on children.

Infants with infantile hypertrophic pyloric stenosis (IHPS) born from 1983 to 1988 and recorded in the California Birth Defects Monitoring Program (CBDMP) database were compared with their birth cohort by demographic characteristics and selected associated birth defects. We identified 1963 cases of IHPS for a cumulative incidence of 1.9 per 1000 livebirths. The cumulative incidence per 1000 livebirths was 2.4 in White, 1.8 in Hispanic, 0.7 in Black, and 0.6 in Asian infants. Between weeks 3-12 after birth, 1871 (95%) IHPS cases were diagnosed. Premature infants were diagnosed with IHPS later than term or post-term infants. The incidence of IHPS declined for those born to maternal age groups of > or = 25 years and, independently, for successive birth ranks. The probandwise concordance rate for IHPS in monozygous twins was less than unity (0.25-0.44), although higher than the concordance for dizygous twins (0.05-0.10). The incidence of Smith-Lemli-Opitz syndrome (SLO) diagnosed in infants with IHPS (3 of 1963) was 157-fold higher than the incidence of SLO diagnosed in the CBDMP population. IHPS occurs in all of the largest racial and ethnic groups in California, most frequently in White and Hispanic infants. Pyloric stenosis presents only within a brief phase of development, which may be delayed in premature infants. A predominant discordance of disease state in monozygous twins implies an aetiological role for undetermined environmental factors. The association between SLO, caused by deficient cholesterol synthesis, and IHPS deserves additional study. Infants with suspected SLO require close observation for the onset of IHPS.

Oral antiviral agents to treat influenza are challenging to administer in the intensive care unit (ICU). We describe 57 critically ill patients treated with the investigational intravenous neuraminidase inhibitor drug peramivir for influenza A (H1N1)pdm09 [pH1N1]. Most received late peramivir treatment following clinical deterioration in the ICU on enterically-administered oseltamivir therapy. The median age was 40 years (range 5 months-81 years). Common clinical complications included pneumonia or acute respiratory distress syndrome requiring mechanical ventilation (54; 95%), sepsis requiring vasopressor support (34/53; 64%), acute renal failure requiring hemodialysis (19/53; 36%) and secondary bacterial infection (14; 25%). Over half (29; 51%) died. When comparing the 57 peramivir-treated cases with 1627 critically ill cases who did not receive peramivir, peramivir recipients were more likely to be diagnosed with pneumonia/acute respiratory distress syndrome (p = 0.0002) or sepsis (p =

Objective To describe clinical and epidemiologic features of 2009 novel influenza A(H1N1) in children. Design Analysis of data obtained from standardized report forms and medical records. Setting Statewide public health surveillance in California. Participants Three hundred forty-five children who were hospitalized with or died of 2009 novel influenza A(H1N1). Main Exposure Laboratory-confirmed 2009 novel influenza A(H1N1). Main Outcome Measures Hospitalization and death. Results From April 23 to August 11, 2009, 345 cases in children younger than 18 years were reported. The median age was 6 years. The hospitalization rate per 100 000 per 110 days was 3.5 (0.97 per 100 000 person-months), with rates highest in infants younger than 6 months (13.9 per 100 000 or 3.86 per 100 000 person-months). Two-thirds (230; 67%) had comorbidities. More than half (163 of 278; 59%) had pneumonia, 94 (27%) required intensive care, and 9 (3%) died; in 3 fatal cases (33%), children had secondary bacterial infections. More than two-thirds (221 of 319; 69%) received antiviral treatment, 44% (88 of 202) within 48 hours of symptom onset. In multivariate analysis, congenital heart disease (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.9-13.5) and cerebral palsy/developmental delay (OR, 3.5; 95% CI, 1.7-7.4) were associated with increased likelihood of intensive care unit admission and/or death; likelihood was decreased in Hispanic (OR, 0.4; 95% CI, 0.2-0.8) and black (OR, 0.3; 95% CI, 0.1-1.0) children compared with white children. Conclusions More than one-quarter of children hospitalized with 2009 novel influenza A(H1N1) reported to the California Department of Public Health required intensive care and/or died. Regardless of rapid test results, when 2009 novel influenza A(H1N1) is circulating, clinicians should maintain a high suspicion in children with febrile respiratory illness and promptly treat those with underlying risk factors, especially infants.

Pandemic influenza A(H1N1) emerged rapidly in California in April 2009. Preliminary comparisons with seasonal influenza suggest that pandemic 2009 influenza A(H1N1) disproportionately affects younger ages and causes generally mild disease.To describe the clinical and epidemiologic features of pandemic 2009 influenza A(H1N1) cases that led to hospitalization or death.Statewide enhanced public health surveillance of California residents who were hospitalized or died with laboratory evidence of pandemic 2009 influenza A(H1N1) infection reported to the California Department of Public Health between April 23 and August 11, 2009.Characteristics of hospitalized and fatal cases.During the study period there were 1088 cases of hospitalization or death due to pandemic 2009 influenza A(H1N1) infection reported in California. The median age was 27 years (range,1-92 years) and 68% (741/1088) had risk factors for seasonal influenza complications. Sixty-six percent (547/833) of those with chest radiographs performed had infiltrates and 31% (340/1088) required intensive care. Rapid antigen tests were falsely negative in 34% (208/618) of cases evaluated. Secondary bacterial infection was identified in 4% (46/1088). Twenty-one percent (183/884) received no antiviral treatment. Overall fatality was 11% (118/1088) and was highest (18%-20%) in persons aged 50 years or older. The most common causes of death were viral pneumonia and acute respiratory distress syndrome.In the first 16 weeks of the current pandemic, the median age of hospitalized infected cases was younger than is common with seasonal influenza. Infants had the highest hospitalization rates and persons aged 50 years or older had the highest mortality rates once hospitalized. Most cases had established risk factors for complications of seasonal influenza.

Context Previous analyses of autism client data reported to the California Department of Developmental Services (DDS) have been interpreted as supporting the hypothesis that autism is caused by exposure to the preservative thimerosal, which contains ethylmercury. The exclusion of thimerosal from childhood vaccines in the United States was accelerated from 1999 to 2001. The Immunization Safety Review Committee of the Institute of Medicine has recommended surveillance of trends in autism as exposure to thimerosal during early childhood has decreased. Objective To determine whether trends in DDS autism client data support the hypothesis that thimerosal exposure is a primary cause of autism. Design, Setting, and Patients Study of time trends in the prevalence by age and birth cohort of children with autism who were active status clients of the DDS from January 1, 1995, through March 31, 2007. Main Outcome Measure Prevalence of autism among children with active status in the DDS. Results The estimated prevalence of autism for children at each year of age from 3 to 12 years increased throughout the study period. The estimated prevalence of DDS clients aged 3 to 5 years with autism increased for each quarter from January 1995 through March 2007. Since 2004, the absolute increase and the rate of increase in DDS clients aged 3 to 5 years with autism were higher than those in DDS clients of the same ages with any eligible condition including autism. Conclusions The DDS data do not show any recent decrease in autism in California despite the exclusion of more than trace levels of thimerosal from nearly all childhood vaccines. The DDS data do not support the hypothesis that exposure to thimerosal during childhood is a primary cause of autism.

Infant botulism is the most common form of human botulism in the United States. In contrast to foodborne and wound botulism, infant botulism results from intra-intestinal production of botulinum toxin following ingestion and germination of Clostridium botulinum spores. In 1989 the California Department of Health Services (CDHS) undertook development of the orphan drug Human Botulism Immune Globulin (BIG-IV) for the treatment of infant botulism. In 1991 BIG-IV Lot 1 was made by plasmapheresis of CDHS staff and other volunteers previously immunized with botulinum toxoid. BIG-IV was evaluated in a statewide, randomized, placebo-controlled clinical trial (RCT) 1992-97 and in a subsequent national open-label study while licensure requirements were being met. RCT patients were enrolled within 72 hours of hospital admission based on clinical criteria; the placebo was identically-packaged, licensed normal human intravenous immune globulin (IGIV). Treatment consisted of a single intravenous infusion of 50 mg/kg of product. The primary efficacy outcome variable was reduction of length and associated cost of hospital stay. Safety was assessed by comparing adverse event rates. Results 122 patients with eventual laboratory-confirmed infant botulism were enrolled during the 5-year statewide RCT (59 BIG-IV, 63 placebo). No adverse event occurred significantly more frequently in treated patients than in control patients, and no bronchospasm, anaphylaxis or deaths occurred in either group. Treatment with BIG-IV reduced mean per-patient hospital stay by 3.1 weeks, from 5.7 to 2.5 weeks (P≤0.0001) and reduced associated mean per-patient hospital costs by $84,600, from approximately $156,200 to approximately $71,600 (2004 dollars). Treatment with BIG-IV also significantly shortened length of ICU stay by ≥60% (P≤0.01), duration of mechanical ventilation by ≥70% (P≤0.001), duration of tube feedings by ≥60% (P=0.001) and mean adverse events by ≥40% (P=0.05). With nationwide open-label BIG-IV distribution since 1998, mean hospital stay of ≥430 patients was further reduced to 2.2 weeks. Aggregate avoided hospital stay for these ≥430 patients totaled 25.0 patient-years and aggregate avoided hospital costs totaled more than $39,500,000. Conclusion BIG-IV is safe and effective treatment for infant botulism and in late 2003 was licensed by the U.S. FDA; CDHS is distributing it nationwide as a public service medicine.

ObjectiveThe Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals if botulinum toxin is used as a biological weapon against a civilian population.ParticipantsThe working group included 23 representatives from academic, government, and private institutions with expertise in public health, emergency management, and clinical medicine.EvidenceThe primary authors (S.S.A. and R.S.) searched OLDMEDLINE and MEDLINE (1960–March 1999) and their professional collections for literature concerning use of botulinum toxin as a bioweapon. The literature was reviewed, and opinions were sought from the working group and other experts on diagnosis and management of botulism. Additional MEDLINE searches were conducted through April 2000 during the review and revisions of the consensus statement.Consensus ProcessThe first draft of the working group's consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group convened to review the first draft in May 1999. Working group members reviewed subsequent drafts and suggested additional revisions. The final statement incorporates all relevant evidence obtained in the literature search in conjunction with final consensus recommendations supported by all working group members.ConclusionsAn aerosolized or foodborne botulinum toxin weapon would cause acute symmetric, descending flaccid paralysis with prominent bulbar palsies such as diplopia, dysarthria, dysphonia, and dysphagia that would typically present 12 to 72 hours after exposure. Effective response to a deliberate release of botulinum toxin will depend on timely clinical diagnosis, case reporting, and epidemiological investigation. Persons potentially exposed to botulinum toxin should be closely observed, and those with signs of botulism require prompt treatment with antitoxin and supportive care that may include assisted ventilation for weeks or months. Treatment with antitoxin should not be delayed for microbiological testing.