Epidemiologic and Clinical Features of Mpox-Associated Deaths - United States, May 10, 2022-March 7, 2023.

As of March 7, 2023, a total of 30,235 confirmed and probable monkeypox (mpox) cases were reported in the United States,† predominantly among cisgender men§ who reported recent sexual contact with another man (1). Although most mpox cases during the current outbreak have been self-limited, cases of severe illness and death have been reported (2-4). During May 10, 2022-March 7, 2023, 38 deaths among persons with probable or confirmed mpox¶ (1.3 per 1,000 mpox cases) were reported to CDC and classified as mpox-associated (i.e., mpox was listed as a contributing or causal factor). Among the 38 mpox-associated deaths, 94.7% occurred in cisgender men (median age = 34 years); 86.8% occurred in non-Hispanic Black or African American (Black) persons. The median interval from symptom onset to death was 68 days (IQR = 50-86 days). Among 33 decedents with available information, 93.9% were immunocompromised because of HIV. Public health actions to prevent mpox deaths include integrated testing, diagnosis, and early treatment for mpox and HIV, and ensuring equitable access to both mpox and HIV prevention and treatment, such as antiretroviral therapy (ART) (5).

Outbreaks of Adenovirus-associated Respiratory Illness on 5 College Campuses in the United States, 2018-2019.

BACKGROUND: Human adenoviruses (HAdVs) are commonly associated with acute respiratory illness. HAdV outbreaks are well documented in congregate military training settings, but less is known about outbreaks on college campuses. During fall 2018 and spring 2019, 5 United States (US) colleges reported increases in HAdV-associated respiratory illness. Investigations were performed to better understand HAdV epidemiology in this setting. METHODS: A case was defined as a student at one of the 5 colleges, with acute respiratory illness and laboratory-confirmed HAdV infection during October 2018-December 2018 or March-May 2019. Available respiratory specimens were typed by HAdV type-specific real-time polymerase chain reaction assays, and for a subset, whole genome sequencing was performed. We reviewed available medical records and cases were invited to complete a questionnaire, which included questions on symptom presentation, social history, and absenteeism. RESULTS: We identified 168 HAdV cases. Median age was 19 (range, 17-22) years and 102 cases (61%) were male. Eleven cases were hospitalized, 10 with pneumonia; 2 cases died. Among questionnaire respondents, 80% (75/94) missed ≥ 1 day of class because of their illness. Among those with a type identified (79%), HAdV types 4 and 7 were equally detected, with frequency of each varying by site. Genome types 4a1 and 7d were identified, respectively, by whole genome sequence analysis. CONCLUSIONS: HAdV respiratory illness was associated with substantial morbidity and missed class time among young, generally healthy adults on 5 US college campuses. HAdVs should be considered a cause of respiratory illness outbreaks in congregate settings such as college campuses.

Underreporting of Hepatitis B and C virus infections - Pennsylvania, 2001-2015.

CONTEXT: In Pennsylvania, reporting of viral hepatitis B (HBV) and viral hepatitis C (HCV) infections to CDC has been mandated since 2002. Underreporting of HBV and HCV infections has long been identified as a problem. Few reports have described the accuracy of state surveillance case registries for recording clinically-confirmed cases of HBV and HCV infections, or the characteristics of populations associated with lower rates of reporting. OBJECTIVE: The primary objective of the current study is to estimate the proportion of HBV and HCV infections that went unreported to the Pennsylvania Department of Health (PDoH), among patients in the Geisinger Health System of Pennsylvania. As a secondary objective, we study the association between underreporting of HBV and HCV infections to PDoH, and the select patient characteristics of interest: sex, age group, race/ethnicity, rural status, and year of initial diagnosis. DESIGN: Per medical record review, the study population was limited to Geisinger Health System patients, residing in Pennsylvania, who were diagnosed with a chronic HBV and/or HCV infection, between 2001 and 2015. Geisinger Health System patient medical records were matched to surveillance records of confirmed cases reported to the Pennsylvania Department of Health (PDoH). To quantify the extent that underreporting occurred among the Geisinger Health System study participants, we calculated the proportion of study participants that were not reported to PDoH as confirmed cases of HBV or HCV infections. An analysis of adjusted prevalence ratio estimates was conducted to study the association between underreporting of HBV and HCV infections to PDoH, and the select patient characteristics of interest. RESULTS: Geisinger Health System patients living with HBV were reported to PDoH 88.4% (152 of 172) of the time; patients living with HCV were reported to PDoH 94.6% (2,257 of 2,386) of the time; and patients who were co-infected with both viruses were reported to PDoH 72.0% (18 of 25) of the time. Patients living with HCV had an increased likelihood of being reported if they were: less than or equal to age 30 vs ages 65+ {PR = 1.2, [95%CI, (1.1, 1.3)]}, and if they received their initial diagnosis of HCV during the 2010-2015 time period vs the 1990-1999 time period {PR = 1.08, [95%CI, (1.05, 1.12)]}. CONCLUSION: The findings in this study are promising, and suggests that PDoH has largely been successful with tracking and monitoring viral hepatitis B and C infections, among persons that were tested for HBV and/or HCV. Additional efforts should be placed on decreasing underreporting rates of HCV infections among seniors (ages 65 and over), and persons who are co-infected with HBV and HCV.

Notes from the field: update on Lyme carditis, groups at high risk, and frequency of associated sudden cardiac death--United States.

On December 13, 2013, MMWR published a report describing three cases of sudden cardiac death associated with Lyme carditis. State public health departments and CDC conducted a follow-up investigation to determine 1) whether carditis was disproportionately common among certain demographic groups of patients diagnosed with Lyme disease, 2) the frequency of death among patients diagnosed with Lyme disease and Lyme carditis, and 3) whether any additional deaths potentially attributable to Lyme carditis could be identified. Lyme disease cases are reported to CDC through the Nationally Notifiable Disease Surveillance System; reporting of clinical features, including Lyme carditis, is optional. For surveillance purposes, Lyme carditis is defined as acute second-degree or third-degree atrioventricular conduction block accompanying a diagnosis of Lyme disease. During 2001-2010, a total of 256,373 Lyme disease case reports were submitted to CDC, of which 174,385 (68%) included clinical information. Among these, 1,876 (1.1%) were identified as cases of Lyme carditis. Median age of patients with Lyme carditis was 43 years (range = 1-99 years); 1,209 (65%) of the patients were male, which is disproportionately larger than the male proportion among patients with other clinical manifestations (p<0.001). Of cases with this information available, 69% were diagnosed during the months of June-August, and 42% patients had an accompanying erythema migrans, a characteristic rash. Relative to patients aged 55-59 years, carditis was more common among men aged 20-39 years, women aged 25-29 years, and persons aged ≥75 years.

Use of nonpharmaceutical interventions to reduce transmission of 2009 pandemic influenza A (pH1N1) in Pennsylvania public schools.

BACKGROUND: School-based recommendations for nonpharmaceutical interventions (NPIs) were issued in response to the threat of 2009 pandemic influenza A (pH1N1). The implementation and effectiveness of these recommendations has not been assessed. METHODS: In November 2009, a Web-based survey of all Pennsylvania public schools was conducted to assess the use of recommended NPIs. RESULTS: Overall, 1040 (31%) of 3351 schools participated in the survey. By fall 2009, 820 (84%) of 979 respondents reported that their school had an influenza plan in place, a 44% higher proportion than in the spring 2009 (p < .01). Most schools communicated health messages (eg, staying home when sick), implemented return to school requirements, and made hand sanitizer available. Schools with a spring influenza plan (N = 568) were less likely to report substantial influenza-like illness (ILI) during the fall wave of influenza than the 299 schools without a spring influenza plan (63% vs 71%, p = .02). This association persisted after controlling for schools with substantial ILI in the spring. CONCLUSION: The reported use of NPIs in participating Pennsylvania public schools improved substantially from spring to fall and was generally consistent with issued recommendations. The proactive implementation of a number of NPIs and the early implementation of communication and education initiatives might have cumulatively reduced the impact of pH1N1 in some schools.

Lower respiratory tract hemorrhage associated with 2009 pandemic influenza A (H1N1) virus infection.

BACKGROUND: Influenza-associated lower respiratory tract hemorrhage (LRTH) has been reported in previous pandemics and is a rare complication of seasonal influenza virus infection. We describe patients with LRTH associated with 2009 pandemic influenza A (H1N1) (pH1N1) virus infection identified from April 2009 to April 2010 in the United States. METHODS: We ascertained patients with pH1N1-associated LRTH through state and local surveillance, the Emerging Infections Program, and CDCs Infectious Diseases Pathology Branch. All patients had influenza A, evidence of pneumonia, and evidence of LRTH. RESULTS: We identified 44 cases; the median number of days from illness onset to clinical signs of LRTH was one. Hemoptysis or respiratory tract bleeding was documented in 40% of pH1N1-associated LRTH cases, often present early during the course of illness. Twenty-one (48%) patients with LRTH had no other hemorrhagic diatheses. Seven (23%) patients with LRTH received antiviral treatment within two days of illness onset. CONCLUSIONS: During influenza season, clinicians should consider influenza infection in the differential diagnosis for patients presenting with hemoptysis or other signs or symptoms of LRTH. While the impact of timing of antiviral therapy on this complication has not been studied, the rapid progression of LRTH may support use of early empiric therapy. Continued investigation is necessary to betterdefine the clinical spectrum of both seasonal influenza- and pH1N1-associated LRTH.

Description and evaluation of the 2009-2010 Pennsylvania Influenza Sentinel School Monitoring System.

OBJECTIVES: We described and evaluated the 2009-2010 Pennsylvania Influenza Sentinel School Monitoring System, a voluntary sentinel network of schools that report data on school absenteeism and visits to the school nurse for influenza-like illness (ILI). METHODS: Participating schools provided daily absenteeism and ILI data on a weekly basis through an online survey. We used participation and weekly response rates to determine acceptability, timeliness, and simplicity. We assessed representativeness by comparing participating schools with nonparticipating schools. We compared monitoring system data with statewide reports of laboratory-confirmed influenza. RESULTS: Of the 3244 Pennsylvania public schools, 367 (11%) enrolled in the system. On average, 79% of enrolled schools completed the survey each week. Although the peak week of elevated absenteeism coincided with the peak of statewide laboratory-confirmed influenza cases, the correlation between absenteeism and state data was nonsignificant (correlation coefficient = 0.10; P = .56). Trends in ILI correlated significantly with state data (correlation coefficient = 0.67; P < .001). CONCLUSIONS: The school-based sentinel system is a simple, acceptable, reliable device for tracking absenteeism and ILI in schools. Further analyses are necessary to determine the comparative value of this system and other influenza surveillance systems.

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.

Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States.

CONTEXT: Early data on pandemic 2009 influenza A(H1N1) suggest pregnant women are at increased risk of hospitalization and death. OBJECTIVE: To describe the severity of 2009 influenza A(H1N1) illness and the association with early antiviral treatment among pregnant women in the United States. DESIGN, SETTING, AND PATIENTS: Surveillance of 2009 influenza A(H1N1) in pregnant women reported to the Centers for Disease Control and Prevention (CDC) with symptom onset from April through December 2009. MAIN OUTCOME MEASURES: Severity of illness (hospitalizations, intensive care unit [ICU] admissions, and deaths) due to 2009 influenza A(H1N1) among pregnant women, stratified by timing of antiviral treatment and pregnancy trimester at symptom onset. RESULTS: We received reports on 788 pregnant women in the United States with 2009 influenza A(H1N1) with symptom onset from April through August 2009. Among those, 30 died (5% of all reported 2009 influenza A[H1N1] influenza deaths in this period). Among 509 hospitalized women, 115 (22.6%) were admitted to an ICU. Pregnant women with treatment more than 4 days after symptom onset were more likely to be admitted to an ICU (56.9% vs 9.4%; relative risk [RR], 6.0; 95% confidence interval [CI], 3.5-10.6) than those treated within 2 days after symptom onset. Only 1 death occurred in a patient who received treatment within 2 days of symptom onset. Updating these data with the CDC's continued surveillance of ICU admissions and deaths among pregnant women with symptom onset through December 31, 2009, identified an additional 165 women for a total of 280 women who were admitted to ICUs, 56 of whom died. Among the deaths, 4 occurred in the first trimester (7.1%), 15 in the second (26.8%), and 36 in the third (64.3%); CONCLUSIONS: Pregnant women had a disproportionately high risk of mortality due to 2009 influenza A(H1N1). Among pregnant women with 2009 influenza A(H1N1) influenza reported to the CDC, early antiviral treatment appeared to be associated with fewer admissions to an ICU and fewer deaths.

An outbreak of hepatitis A associated with green onions.

BACKGROUND: In November 2003, a large hepatitis A outbreak was identified among patrons of a single Pennsylvania restaurant. We investigated the cause of the outbreak and factors that contributed to its unprecedented size. METHODS: Demographic and clinical outcome data were collected from patients with laboratory confirmation of hepatitis A, and restaurant workers were tested for hepatitis A. A case-control study was conducted among patrons who dined at the restaurant between October 3 and October 6, 2003. Sequence analysis was performed on a 315-nucleotide region of viral RNA extracted from serum specimens. RESULTS: Of 601 patients identified, 3 died; at least 124 were hospitalized. Of 425 patients who recalled a single dining date at the restaurant, 356 (84 percent) had dined there between October 3 and October 6. Among 240 patients in the case-control study, 218 had eaten mild salsa (91 percent), as compared with 45 of 130 controls (35 percent) (odds ratio, 19.6; 95 percent confidence interval, 11.0 to 34.9) for whom data were available. A total of 98 percent of patients and 58 percent of controls reported having eaten a menu item containing green onions (odds ratio, 33.3; 95 percent confidence interval, 12.8 to 86.2). All restaurant workers were tested, but none were identified who could have been the source of the outbreak. Sequences of hepatitis A virus from all 170 patients who were tested were identical. Mild salsa, which contained green onions grown in Mexico, was prepared in large batches at the restaurant and provided to all patrons. CONCLUSIONS: Green onions that were apparently contaminated before arrival at the restaurant caused this unusually large foodborne outbreak of hepatitis A. The inclusion of contaminated green onions in large batches that were served to all customers contributed to the size of the outbreak.

Trihalomethane levels in home tap water and semen quality.

BACKGROUND: Trihalomethanes (THMs) are byproducts of drinking water chlorination whose effects on semen quality have not been previously studied in humans. METHODS: We examined the relationship of THMs to semen quality in 157 healthy men from couples without known risk factors for infertility. Total THM (TTHM) levels were assigned based on water utility measurements taken during the 90 days preceding semen collection. We analyzed continuous semen parameters in relation to total and individual THMs, adjusting for potential confounders by using repeated measures analyses. RESULTS: TTHM level was not associated with decrements in semen quality. Percent normal morphology decreased and percent head defects increased at higher levels of an ingestion metric (TTHM multiplied by cold home tap water consumption). At the highest level of the ingestion metric (>160 mug/L x glasses/day, which is equivalent to >2 glasses/day of water containing 80 mug/L) we observed a difference of -7.1 (95% confidence interval = -12.7 to -1.6) for percent morphologically normal sperm compared with the lowest level (

Chlorination by-products in drinking water and menstrual cycle function.

We analyzed data from a prospective study of menstrual cycle function and early pregnancy loss to explore further the effects of trihalomethanes (THM) on reproductive end points. Premenopausal women ((italic)n(/italic) = 403) collected urine samples daily during an average of 5.6 cycles for measurement of steroid metabolites that were used to define menstrual parameters such as cycle and phase length. Women were asked about consumption of various types of water as well as other habits and demographics. A THM level was estimated for each cycle based on residence and quarterly measurements made by water utilities during a 90-day period beginning 60 days before the cycle start date. We found a monotonic decrease in mean cycle length with increasing total THM (TTHM) level; at > 60 microg/L, the adjusted decrement was 1.1 days [95% confidence interval (CI), -1.8 to -0.40], compared with less than or equal to 40 microg/L. This finding was also reflected as a reduced follicular phase length (difference -0.94 day; 95% CI, -1.6 to -0.24). A decrement in cycle and follicular phase length of 0.18 days (95% CI, -0.29 to -0.07) per 10 microg/L unit increase in TTHM concentration was found. There was little association with luteal phase length, menses length, or cycle variability. Examining the individual THMs by quartile, we found the greatest association with chlorodibromomethane or the sum of the brominated compounds. Incorporating tap water consumption showed a similar pattern of reduced cycle length with increasing TTHM exposure. These findings suggest that THM exposure may affect ovarian function and should be confirmed in other studies.

Residents' perspectives on the use of the Internet to improve infectious disease reporting.

Reports of infectious diseases to local and state public health agencies are often delayed and incomplete. Some of the clinicians charged with the responsibility for making notifications encounter various difficulties in reporting. These may include heavy patient loads that make it easy to forget to file reports, or cumbersome disease reporting mechanisms and systems. For some percentage of practitioners, knowledge of what and when to report infectious diseases is less than optimal. However, it is not clear how reporting methods or systems could be designed or improved, owing to lack of data on physicians' knowledge and views about them. We conducted a survey of resident physicians at three university teaching hospitals in Pennsylvania to ascertain their knowledge about reporting timeframe and responsibility, as well as their attitudes toward various methods to enhance disease reporting.

Ovarian hormones in premenopausal women: variation by demographic, reproductive and menstrual cycle characteristics.

BACKGROUND: Ovarian function influences many areas of concern in women's health, including breast cancer and other chronic diseases. However, ovarian function has been little studied in healthy, premenopausal women, partly because of cyclical variation. METHODS: We measured biomarkers of ovarian function (daily urinary metabolites of estrogen and progesterone) among 411 women age 18-39 years, who were Kaiser Permanente members in Northern California in 1990-1991. We have summarized the hormone metabolite levels of about 1,500 cycles and examined their associations with demographic and menstrual cycle characteristics. RESULTS: Cycles with a short follicular phase showed elevations of 10-13% in both baseline (days 1-5) and average follicular-phase estrogen metabolite levels, as well as some elevations in progesterone metabolites. Progesterone metabolite levels were directly related to the length of the luteal phase. Compared with whites, Hispanics had estrogen metabolite levels that were 7-13% higher in the follicular and luteal phases, whereas nonwhite, non-Hispanic women (primarily Asians) had slightly lower levels. Generally, women with a prior pregnancy or those with a later age at menarche had lower estrogen metabolite levels, whereas women with prior induced abortions had higher levels. Luteal-phase progesterone metabolite levels tended to be lower among women who were overweight, were less educated, were older at their first livebirth, or had an induced abortion. CONCLUSIONS: Some menstrual cycle characteristics provide a crude surrogate of the hormonal milieu, particularly luteal-phase length and progesterone levels. Hormone levels varied by reproductive characteristics, potentially explaining their relevance to breast cancer risk.

Assessing exposure in epidemiologic studies to disinfection by-products in drinking water: report from an international workshop.

The inability to accurately assess exposure has been one of the major shortcomings of epidemiologic studies of disinfection by-products (DBPs) in drinking water. A number of contributing factors include a) limited information on the identity, occurrence, toxicity, and pharmacokinetics of the many DBPs that can be formed from chlorine, chloramine, ozone, and chlorine dioxide disinfection; b) the complex chemical interrelationships between DBPs and other parameters within a municipal water distribution system; and c) difficulties obtaining accurate and reliable information on personal activity and water consumption patterns. In May 2000, an international workshop was held to bring together various disciplines to develop better approaches for measuring DBP exposure for epidemiologic studies. The workshop reached consensus about the clear need to involve relevant disciplines (e.g., chemists, engineers, toxicologists, biostatisticians and epidemiologists) as partners in developing epidemiologic studies of DBPs in drinking water. The workshop concluded that greater collaboration of epidemiologists with water utilities and regulators should be encouraged in order to make regulatory monitoring data more useful for epidemiologic studies. Similarly, exposure classification categories in epidemiologic studies should be chosen to make results useful for regulatory or policy decision making.