Adverse Events Associated With Treatment for Pan-Susceptible Tuberculosis in San Francisco.

Of 373 patients treated for drug-susceptible tuberculosis, 35.4% (46.2% aged ≥65 years) developed moderate/severe adverse events that required treatment interruption (34.8%), first-line drug discontinuation (26.2%, primarily pyrazinamide), second-line drug initiation (30.0%), and treatment duration up to 3.8 months longer. More safe and effective options are needed, including for the elderly.

Uniting for Ukraine Tuberculosis Screening Experience, San Francisco, California, USA.

Ukraine surveillance data suggest high tuberculosis (TB) incidence, including multidrug resistance. Of 299 newcomers from Ukraine screened in San Francisco, California, USA, by using an interferon-γ-release-assay (IGRA) and chest radiograph, 7.4% were IGRA positive and 1 had laboratory-confirmed pansusceptible TB. Screening with IGRA and chest radiograph can help characterize TB risk.

Lessons From Mass-Testing for Coronavirus Disease 2019 in Long-Term Care Facilities for the Elderly in San Francisco.

Coronavirus disease 2019 can cause significant mortality in the elderly in long-term care facilities (LTCF). We describe 4 LTCF outbreaks where mass testing identified a high proportion of asymptomatic infections (4%-41% in healthcare workers and 20%-75% in residents), indicating that symptom-based screening alone is insufficient for monitoring for COVID-19 transmission.

Tuberculosis-Associated Hospitalizations and Deaths after COVID-19 Shelter-In-Place, San Francisco, California, USA.

A mandated shelter-in-place and other restrictions associated with the coronavirus disease pandemic precipitated a decline in tuberculosis diagnoses in San Francisco, California, USA. Several months into the pandemic, severe illness resulting in hospitalization or death increased compared with prepandemic levels, warranting heightened vigilance for tuberculosis in at-risk populations.

Fatal meningococcal disease in a laboratory worker--California, 2012.

Occupationally acquired meningococcal disease is rare. Adherence to recommendations for safe handling of Neisseria meningitidis in the laboratory greatly reduces the risk for transmission to laboratory workers. A California microbiologist developed fatal serogroup B meningococcal disease after working with N. meningitidis patient isolates in a research laboratory (laboratory A). The California Department of Public Health (CDPH), the local health department, the California Division of Occupational Safety and Health (CalOSHA), and the federal Occupational Safety and Health Administration (OSHA) collaborated on an investigation of laboratory A, which revealed several breaches in recommended laboratory practice for safe handling of N. meningitidis, including manipulating cultures on the bench top. Additionally, laboratory workers had not been offered meningococcal vaccine in accordance with Advisory Committee on Immunization Practices (ACIP) recommendations and CalOSHA Aerosol Transmissible Diseases Standard requirements. In accordance with OSHA and CalOSHA regulations, laboratory staff members must receive laboratory biosafety training and use appropriate personal protective equipment, and those who routinely work with N. meningitidis isolates should receive meningococcal vaccine.

Experience With Four-Month Rifapentine and Moxifloxacin-Based Tuberculosis Treatment in San Francisco.

Background: A multicountry randomized controlled trial has demonstrated that pan-susceptible pulmonary tuberculosis (TB) can be successfully treated with a 4-month regimen of daily isoniazid, rifapentine, moxifloxacin, and pyrazinamide (HPMZ). We piloted HPMZ in San Francisco (SF) using a modified version of the US Centers for Disease Control and Prevention HPMZ treatment guidelines. Methods: In this retrospective cohort, patients consecutively referred to SF TB clinic were evaluated for HPMZ eligibility based on preestablished inclusion/exclusion criteria. All underwent evaluation and management according to national recommendations. We reviewed the medical records of those initiated on HPMZ. Results: From August 2021 to December 2023, 30 (18.8%) of 160 patients diagnosed with active TB met HPMZ inclusion criteria; of these, 22 (13.8%) started HPMZ. The median age (range) was 32.5 (14-86) years, 17 (77.3%) were otherwise healthy, and 19 (86.4%) had pulmonary TB, including 7 (36.8%) with cavitary disease. Eighteen (81.8%) patients had an adverse event, with 11 (50%) prematurely discontinuing HPMZ; the most common adverse events were vomiting, elevated transaminases, and rash. To date, 9 (40.9%) have completed treatment, with most achieving criteria for cure. One patient was diagnosed with possible TB recurrence and restarted standard TB treatment. Conclusions: Our experience, with half of patients to date prematurely discontinuing HPMZ, illustrates the challenge of extrapolating findings from TB clinical trials commonly conducted in high-incidence, non-US settings to US clinical practice. Further experience may help identify best practices for implementing HPMZ, including identifying predictors of which patients may be most likely to benefit from and tolerate this regimen.

Severe 2009 H1N1 influenza in pregnant and postpartum women in California.

BACKGROUND: Like previous epidemic and pandemic diseases, 2009 pandemic influenza A (H1N1) may pose an increased risk of severe illness in pregnant women. METHODS: Statewide surveillance for patients who were hospitalized with or died from 2009 H1N1 influenza was initiated by the California Department of Public Health. We reviewed demographic and clinical data reported from April 23 through August 11, 2009, for all H1N1-infected, reproductive-age women who were hospitalized or died--nonpregnant women, pregnant women, and postpartum women (those who had delivered < or = 2 weeks previously). RESULTS: Data were reported for 94 pregnant women, 8 postpartum women, and 137 nonpregnant women of reproductive age who were hospitalized with 2009 H1N1 influenza. Rapid antigen tests were falsely negative in 38% of the patients tested (58 of 153). Most pregnant patients (89 of 94 [95%]) were in the second or third trimester, and approximately one third (32 of 93 [34%]) had established risk factors for complications from influenza other than pregnancy. As compared with early antiviral treatment (administered < or = 2 days after symptom onset) in pregnant women, later treatment was associated with admission to an intensive care unit (ICU) or death (relative risk, 4.3). In all, 18 pregnant women and 4 postpartum women (total, 22 of 102 [22%]) required intensive care, and 8 (8%) died. Six deliveries occurred in the ICU, including four emergency cesarean deliveries. The 2009 H1N1 influenza-specific maternal mortality ratio (the number of maternal deaths per 100,000 live births) was 4.3. CONCLUSIONS: 2009 H1N1 influenza can cause severe illness and death in pregnant and postpartum women; regardless of the results of rapid antigen testing, prompt evaluation and antiviral treatment of influenza-like illness should be considered in such women. The high cause-specific maternal mortality rate suggests that 2009 H1N1 influenza may increase the 2009 maternal mortality ratio in the United States.

A population-based study of neurologic manifestations of severe influenza A(H1N1)pdm09 in California.

BACKGROUND: Reported influenza-associated neurologic complications are generally limited to case series or case reports. We conducted a population-based study of neurologic manifestations associated with severe and fatal influenza A(H1N1)pdm09 (2009 H1N1) cases. METHODS: Medical records of patients with fatal or severe (hospitalized in intensive care unit) laboratory-confirmed 2009 H1N1 reported to the California Department of Public Health from 15 April 2009 through 31 December 2009 were reviewed to identify those with primary neurological manifestations. Cases with secondary neurologic manifestations (eg, hypoxia) were excluded. Primary influenza-associated neurologic complications (INCs) were classified into 4 groups: encephalopathy/encephalitis, seizures, meningitis, and other. Severe 2009 H1N1-associated neurologic incidence was calculated by using estimates of 2009 H1N1 illnesses in California. RESULTS: Of 2069 reported severe or fatal 2009 H1N1 cases, 419 (20%) had neurologic manifestations. Of these, 77 (18%) met our definition of INCs: encephalopathy/encephalitis (n = 29), seizures (n = 44), meningitis (n = 3), and other (Guillain-Barré Syndrome) (n = 1). The median age was 9 years (range, 4 months-92 years); the highest rate of disease was among pediatric Asian/Pacific Islanders (12.79 per 1,000,000) compared with pediatric white, non-Hispanics (3.09 per 1,000,000), Hispanics (4.58 per 1,000,000), and blacks (6.57 per 1,000,000). The median length of stay (LOS) was 4 days (range, 1-142), and there were 4 fatalities. The estimated incidence of INCs was 1.2 per 100,000 symptomatic 2009 H1N1 illnesses. CONCLUSIONS: Influenza-associated neurologic complications were observed in 4% of patients with fatal or severe 2009 H1N1. They were observed most often in pediatric patients, and Asian/Pacific Islanders appear to be overrepresented compared with the California population. Most patients with INCs had a relatively short LOS, and there were few fatalities.

Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1)pdm09.

BACKGROUND: Neuraminidase inhibitor (NAI) antiviral drugs can shorten the duration of uncomplicated influenza when administered early (<48 hours after illness onset) to otherwise healthy outpatients, but the optimal timing of effective therapy for critically ill patients is not well established. 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 < .0001). Treatment initiated within 5 days after symptom onset was associated with improved survival compared to those never treated (P < .05). 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.

HIV-infected hospitalized patients with 2009 pandemic influenza A (pH1N1)--United States, spring and summer 2009.

We describe the clinical findings of HIV-infected patients hospitalized with 2009 pandemic influenza A (pH1N1). Data were derived from 3 separate case series in the United States. Among 911 adults hospitalized with pH1N1 influenza, 31 (3.4%) were HIV infected compared with an HIV prevalence of 0.45% in the general US adult population. HIV-infected influenza patients experienced similar rates of intensive care unit admission (29% vs 34%) and death (13% vs 13%) compared with non-HIV-infected patients. Among HIV-infected patients with available data, 14 (50%) of 28 patients had a CD4 cell count <200 cells/µL, which was not associated with an increased risk of an intensive care unit admission or death. Overall, 25 (81%) HIV-infected patients received influenza antiviral therapy, but treatment was initiated within 48 h of illness onset in only 33% of cases. Clinicians should consider early empiric influenza antiviral treatment in HIV-infected patients presenting with suspected influenza.

A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1).

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.

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.

2009 pandemic influenza A (H1N1) virus infection in postpartum women in California.

OBJECTIVE: The objective of the study was to characterize severe illness because of the 2009 pandemic influenza A (H1N1) infection in postpartum women. STUDY DESIGN: We reviewed case reports of infected hospitalized postpartum (≤ 6 months from delivery) women identified through statewide surveillance in California. From April 23 through August 11, 2009, all hospitalizations and/or deaths were reported. After August 11, reporting was limited to cases requiring intensive care or deaths. RESULTS: From April 23 to December 31, 2009, 15 cases were reported; 11 (73%) had symptom onset within 7 days postpartum. Of 10 hospitalized cases reported through August 11, 4 required intensive care, 3 required mechanical ventilation, and 2 died. Of 5 cases requiring intensive care reported after August 11, all required mechanical ventilation and 1 died. Overall, 6 (43%) received antivirals within 48 hours of symptom onset. CONCLUSION: The 2009 H1N1 can cause severe illness in postpartum women, especially in the first week following delivery.

Identification of cardioviruses related to Theiler's murine encephalomyelitis virus in human infections.

Cardioviruses comprise a genus of picornaviruses that cause severe illnesses in rodents, but little is known about the prevalence, diversity, or spectrum of disease of such agents among humans. A single cardiovirus isolate, Saffold virus, was cultured in 1981 in stool from an infant with fever. Here, we describe the identification of a group of human cardioviruses that have been cloned directly from patient specimens, the first of which was detected using a pan-viral microarray in respiratory secretions from a child with influenza-like illness. Phylogenetic analysis of the nearly complete viral genome (7961 bp) revealed that this virus belongs to the Theiler's murine encephalomyelitis virus (TMEV) subgroup of cardioviruses and is most closely related to Saffold virus. Subsequent screening by RT-PCR of 719 additional respiratory specimens [637 (89%) from patients with acute respiratory illness] and 400 cerebrospinal fluid specimens from patients with neurological disease (aseptic meningitis, encephalitis, and multiple sclerosis) revealed no evidence of cardiovirus infection. However, screening of 751 stool specimens from 498 individuals in a gastroenteritis cohort resulted in the detection of 6 additional cardioviruses (1.2%). Although all 8 human cardioviruses (including Saffold virus) clustered together by phylogenetic analysis, significant sequence diversity was observed in the VP1 gene (66.9%-100% pairwise amino acid identities). These findings suggest that there exists a diverse group of novel human Theiler's murine encephalomyelitis virus-like cardioviruses that hitherto have gone largely undetected, are found primarily in the gastrointestinal tract, can be shed asymptomatically, and have potential links to enteric and extraintestinal disease.

Timely intervention and control of a novel coronavirus (COVID-19) outbreak at a large skilled nursing facility-San Francisco, California, 2020.

OBJECTIVE: To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled-nursing facility (SNF), and the strategies that controlled transmission. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted during March 22-May 4, 2020, among all staff and residents at a 780-bed SNF in San Francisco, California. METHODS: Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPSs) in units with confirmed cases. Cases were confirmed by real-time reverse transcription-polymerase chain reaction testing for SARS-CoV-2, and whole-genome sequencing (WGS) was used to characterize viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact with a confirmed case; restricting movement between units; implementing surgical face masking facility-wide; and the use of recommended PPE (ie, isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases. RESULTS: Of 725 staff and residents tested through targeted testing and serial PPSs, 21 (3%) were SARS-CoV-2 positive: 16 (76%) staff and 5 (24%) residents. Fifteen cases (71%) were linked to a single unit. Targeted testing identified 17 cases (81%), and PPSs identified 4 cases (19%). Most cases (71%) were identified before IPC interventions could be implemented. WGS was performed on SARS-CoV-2 isolates from 4 staff and 4 residents: 5 were of Santa Clara County lineage and the 3 others were distinct lineages. CONCLUSIONS: Early implementation of targeted testing, serial PPSs, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.

Invasive group A streptococcal infection concurrent with 2009 H1N1 influenza.

We describe 10 patients with 2009 H1N1 influenza and concurrent invasive group A streptococcal infection with marked associated morbidity and mortality. Seven patients required intensive care, 8 required mechanical ventilation, and 7 died. Five of the patients, including 4 of the fatalities, were previously healthy.

Rapid influenza antigen test for diagnosis of pandemic (H1N1) 2009.

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.

H1N1 2009 influenza virus infection during pregnancy in the USA.

BACKGROUND: Pandemic H1N1 2009 influenza virus has been identified as the cause of a widespread outbreak of febrile respiratory infection in the USA and worldwide. We summarised cases of infection with pandemic H1N1 virus in pregnant women identified in the USA during the first month of the present outbreak, and deaths associated with this virus during the first 2 months of the outbreak. METHODS: After initial reports of infection in pregnant women, the US Centers for Disease Control and Prevention (CDC) began systematically collecting additional information about cases and deaths in pregnant women in the USA with pandemic H1N1 virus infection as part of enhanced surveillance. A confirmed case was defined as an acute respiratory illness with laboratory-confirmed pandemic H1N1 virus infection by real-time reverse-transcriptase PCR or viral culture; a probable case was defined as a person with an acute febrile respiratory illness who was positive for influenza A, but negative for H1 and H3. We used population estimates derived from the 2007 census data to calculate rates of admission to hospital and illness. FINDINGS: From April 15 to May 18, 2009, 34 confirmed or probable cases of pandemic H1N1 in pregnant women were reported to CDC from 13 states. 11 (32%) women were admitted to hospital. The estimated rate of admission for pandemic H1N1 influenza virus infection in pregnant women during the first month of the outbreak was higher than it was in the general population (0.32 per 100 000 pregnant women, 95% CI 0.13-0.52 vs 0.076 per 100 000 population at risk, 95% CI 0.07-0.09). Between April 15 and June 16, 2009, six deaths in pregnant women were reported to the CDC; all were in women who had developed pneumonia and subsequent acute respiratory distress syndrome requiring mechanical ventilation. INTERPRETATION: Pregnant women might be at increased risk for complications from pandemic H1N1 virus infection. These data lend support to the present recommendation to promptly treat pregnant women with H1N1 influenza virus infection with anti-influenza drugs. FUNDING: US CDC.