William A. Bower

Clinical Framework and Medical Countermeasure Use During an Anthrax Mass-Casualty Incident.

In 2014, CDC published updated guidelines for the prevention and treatment of anthrax (Hendricks KA, Wright ME, Shadomy SV, et al. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20[2]. Available at http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article.htm). These guidelines provided recommended best practices for the diagnosis and treatment of persons with naturally occurring or bioterrorism-related anthrax in conventional medical settings. An aerosolized release of Bacillus anthracis spores over densely populated areas could become a mass-casualty incident. To prepare for this possibility, the U.S. government has stockpiled equipment and therapeutics (known as medical countermeasures [MCMs]) for anthrax prevention and treatment. However, previously developed, publicly available clinical recommendations have not addressed the use of MCMs or clinical management during an anthrax mass-casualty incident, when the number of patients is likely to exceed the ability of the health care infrastructure to provide conventional standards of care and supplies of MCMs might be inadequate to meet the demand required. To address this gap, in 2013, CDC conducted a series of systematic reviews of the scientific literature on anthrax to identify evidence that could help clinicians and public health authorities set guidelines for intravenous antimicrobial and antitoxin use, diagnosis of anthrax meningitis, and management of common anthrax-specific complications in the setting of a mass-casualty incident. Evidence from these reviews was presented to professionals with expertise in anthrax, critical care, and disaster medicine during a series of workgroup meetings that were held from August 2013 through March 2014. In March 2014, a meeting was held at which 102 subject matter experts discussed the evidence and adapted the existing best practices guidance to a clinical use framework for the judicious, efficient, and rational use of stockpiled MCMs for the treatment of anthrax during a mass-casualty incident, which is described in this report. This report addresses elements of hospital-based acute care, specifically antitoxins and intravenous antimicrobial use, and the diagnosis and management of common anthrax-specific complications during a mass-casualty incident. The recommendations in this report should be implemented only after predefined triggers have been met for shifting from conventional to contingency or crisis standards of care, such as when the magnitude of cases might lead to impending shortages of intravenous antimicrobials, antitoxins, critical care resources (e.g., chest tubes and chest drainage systems), or diagnostic capability. This guidance does not address primary triage decisions, anthrax postexposure prophylaxis, hospital bed or workforce surge capacity, or the logistics of dispensing MCMs. Clinicians, hospital administrators, state and local health officials, and planners can use these recommendations to assist in the development of crisis protocols that will ensure national preparedness for an anthrax mass-casualty incident.

An Outbreak of Hepatitis A Associated with Green Onions

Forty-three cases of serologically confirmed hepatitis A occurred among individuals who ate at restaurant A in Ohio in 1998. Serum samples from all restaurant A employees who worked during the exposure period were negative for IgM antibodies to hepatitis A virus (HAV). A matched case-control study determined that foods containing green onions, which were eaten by 38 (95%) of 40 case patients compared with 30 (50%) of 60 control subjects, were associated with illness (matched odds ratio, 12.7; 95% confidence interval, 2.6-60.8). Genetic sequences of viral isolates from 14 case patients were identical to each other and to those of viral isolates from 3 patients with cases of hepatitis A acquired in Mexico. Although the implicated green onions, which could have come from one of 2 Mexican farms or from a Californian farm, were widely distributed, no additional green onion-associated cases were detected. More sensitive methods are needed to detect foodborne hepatitis A. A better understanding of how HAV might contaminate raw produce would aid in developing prevention strategies.

Duration of Viremia in Hepatitis A Virus Infection

The duration of viremia and time course for development of IgM antibodies were determined prospectively in natural and experimental hepatitis A virus (HAV) infection. Serial serum samples from HAV-infected men (n=13) and experimentally infected chimpanzees (n=5) were examined by nested reverse-transcriptase polymerase chain reaction analysis to detect HAV RNA and by ELISA to detect IgM antibodies to HAV. Among infected humans, HAV RNA was detected an average of 17 days before the alanine aminotransferase peak, and viremia persisted for an average of 79 days after the liver enzyme peak. The average duration of viremia was 95 days (range, 36-391 days). Results were similar in chimpanzees. In addition, HAV RNA was detected in serum of humans and chimpanzees several days before IgM antibodies to HAV were detected. These results indicate that adults with HAV infection are viremic for as long as 30 days before the onset of symptoms and that the duration of viremia may be longer than previously described.

Population-Based Surveillance for Acute Liver Failure

OBJECTIVES:Most U.S. studies of acute liver failure (ALF) patients have been conducted at tertiary care liver transplantation centers. The aim of this study was to conduct population-based surveillance for ALF.METHODS:We conducted population-based surveillance for ALF within the 8 counties comprising Metropolitan Atlanta between November 2000 and October 2004. ALF cases were defined as the presence of coagulopathy, any grade of hepatic encephalopathy within 26 wk of illness onset, and no history of underlying liver disease. A questionnaire was administered and medical records were reviewed to determine clinical features, etiologies, and outcomes.RESULTS:A total of 65 cases were enrolled, yielding an annualized incidence for all causes of ALF of 5.5 (95% CI 4.3–7.0) per million. Acetaminophen (APAP)-related ALF was the most common (41%) etiology in adults while ALF of undetermined etiology was most common (38%) in children, followed by APAP-related ALF (25%). Unintentional APAP overdose was the most common type (61%) of APAP-related cause. Blacks were more likely than other races to have ALF of undetermined etiology (32% vs 11%). Overall mortality was 40%, with 27 (42%) surviving with supportive care alone and 8 (12%) requiring orthotopic liver transplantation.CONCLUSIONS:Our population-based study suggests approximately 1,600 ALF cases occur in the United States each year. Consistent with findings from studies conducted exclusively at liver transplantation centers, APAP-related ALF was the most common etiology. Increased awareness of APAP-related ALF in the medical community may limit future cases. More research is warranted into ALF of undetermined etiology, especially in children.

Persistence of Protection Against Hepatitis B Virus Infection Among Adolescents Vaccinated With Recombinant Hepatitis B Vaccine Beginning at Birth : A 15-Year Follow-Up Study

Background: Long-term follow-up studies of populations that received recombinant hepatitis B (HB) vaccination beginning at birth are limited. Methods: Micronesian adolescents who had received 3 doses of recombinant HB vaccine (Recombivax 5 μg at birth, 2.5 μg at 2 months, 2.5 μg at 6 months) and tested negative for antibody to HB core antigen (anti-HBc) 2 years after primary vaccination (baseline testing) were followed up 15 years after primary vaccination. After testing for anti-HBc, HB surface antigen (HBsAg), and antibody to HBsAg (anti-HBs), participants received a booster dose of HB vaccine. An anamnestic response was defined as an increase in anti-HBs concentrations to a level ≥10 mIU/mL 14 days postbooster. Results: Of the 105 participants, 42 (40.0%) had anti-HBs concentrations ≥10 mIU/mL on baseline testing. At 15 years, 8 (7.6%) were anti-HBc positive; none were HBsAg positive. Of the remaining 97, 7 (7.3%) had anti-HBs concentrations ≥10 mIU/mL. Of the 96 who received a booster dose, 46 (47.9%) had an anamnestic response; final antibody concentrations were 10-99 mIU/mL for 17 (17.7%) and >100 mIU/mL for 29 (30.2%). Participants with anti-HBs concentrations ≥10 mIU/mL on baseline testing were more likely to have an anamnestic response at 15 years [26/39 (66.7%) versus 20/57 (35.1%); P = 0.003]. Conclusions: Fifteen years after primary vaccination starting at birth, 8% of participants had evidence of past HB virus infection, but none had chronic infection. Absence of an anamnestic response to an additional vaccine dose, seen in half of participants, might indicate waning immunity.

Sequence Heterogeneity of TT Virus and Closely Related Viruses

ABSTRACT TT virus (TTV) is a recently discovered infectious agent originally obtained from transfusion-related hepatitis. However, the causative link between the TTV infection and liver disease remains uncertain. Recent studies demonstrated that genome sequences of different TTV strains are significantly divergent. To assess genetic heterogeneity of the TTV genome in more detail, a sequence analysis of PCR fragments (271 bp) amplified from open reading frame 1 (ORF1) was performed. PCR fragments were amplified from 5 to 40% of serum specimens obtained from patients with different forms of hepatitis who reside in different countries (e.g., China, Egypt, Vietnam, and the United States) and from normal human specimens obtained from U.S. residents. A total of 170 PCR fragments were sequenced and compared to sequences derived from the corresponding TTV genome region deposited in GenBank. Genotypes 2 and 3 were found to be significantly more genetically related than any other TTV genotype. Moreover, three sequences were shown to be almost equally related to both genotypes 2 and 3. These observations suggest a merger of genotypes 2 and 3 into one genotype, 2/3. Additionally, five new groups of TTV sequences were identified. One group represents a new genotype, whereas the other four groups were shown to be more evolutionary distant from all known TTV sequences. The evolutionary distances between these four groups were also shown to be greater than between TTV genotypes. The phylogenetic analysis suggested that these four new genetic groups represent closely related yet different viral species. Thus, TTV exists as a “swarm” of at least five closely related but different viruses. These observations suggest a high degree of genetic complexity within the TTV population. The finding of the additional TTV-related species should be taken into consideration when the association between TTV infections and human diseases of unknown etiology is studied.

Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults.

The Centers for Disease Control and Prevention convened panels of anthrax experts to review and update guidelines for anthrax postexposure prophylaxis and treatment. The panels included civilian and military anthrax experts and clinicians with experience treating anthrax patients. Specialties represented included internal medicine, pediatrics, obstetrics, infectious disease, emergency medicine, critical care, pulmonology, hematology, and nephrology. Panelists discussed recent patients with systemic anthrax; reviews of published, unpublished, and proprietary data regarding antimicrobial drugs and anthrax antitoxins; and critical care measures of potential benefit to patients with anthrax. This article updates antimicrobial postexposure prophylaxis and antimicrobial and antitoxin treatment options and describes potentially beneficial critical care measures for persons with anthrax, including clinical procedures for infected nonpregnant adults. Changes from previous guidelines include an expanded discussion of critical care and clinical procedures and additional antimicrobial choices, including preferred antimicrobial drug treatment for possible anthrax meningitis.

Transmission of Cryptococcus neoformans by Organ Transplantation

BACKGROUND This article describes transmission of Cryptococcus neoformans by solid organ transplantation. METHODS We reviewed medical records and performed molecular genotyping of isolates to determine potential for donor transmission of Cryptococcus. RESULTS Cryptococcosis was diagnosed in 3 recipients of organs from a common donor with an undifferentiated neurologic condition at the time of death. Cryptococcal meningoencephalitis was later diagnosed in the donor at autopsy. The liver and 1 kidney recipient developed cryptococcemia and pneumonia and the other kidney recipient developed cryptococcemia and meningitis; 2 patients recovered with prolonged antifungal therapy. We tested 4 recipient isolates with multilocus sequence typing and found they had identical alleles. CONCLUSIONS Our investigation documents the transmission of Cryptococcus neoformans by organ transplantation. Evaluation for cryptococcosis in donors with unexplained neurologic symptoms should be strongly considered.

Ongoing transmission of hepatitis B virus infection among inmates at a state correctional facility

OBJECTIVES We sought to determine hepatitis B virus (HBV) infection prevalence, associated exposures, and incidence among male inmates at a state correctional facility. METHODS A cross-sectional serological survey was conducted in June 2000, and susceptible inmates were retested in June 2001. RESULTS At baseline, 230 inmates (20.5%; 95% confidence interval [CI]=18.2%, 22.9%) exhibited evidence of HBV infection, including 11 acute and 11 chronic infections. Inmates with HBV infection were more likely than susceptible inmates to have injected drugs (38.8% vs 18.0%; adjusted prevalence odds ratio [OR]=3.0; 95% CI=1.9, 4.9), to have had more than 25 female sex partners (27.7% vs 17.5%; adjusted prevalence OR=2.0; 95% CI=1.4, 3.0), and to have been incarcerated for more than 14 years (38.4% vs 17.6%; adjusted prevalence OR=1.7; 95% CI=1.1, 2.6). One year later, 18 (3.6%) showed evidence of new HBV infection. Among 19 individuals with infections, molecular analysis identified 2 clusters involving 10 inmates, each with a unique HBV sequence. CONCLUSIONS We documented ongoing HBV transmission at a state correctional facility. Similar transmission may occur at other US correctional facilities and could be prevented by vaccination of inmates.

SARS Surveillance during Emergency Public Health Response, United States, March-July 2003

In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of missing convalescent-phase serum specimens. Thirty-one percent (124/398) of case-patients were hospitalized; none died. Travel was the most common epidemiologic link (329/398, 83%), and mainland China was the affected area most commonly visited. One case of possible household transmission was reported, and no laboratory-confirmed infections occurred among healthcare workers. Successes and limitations of this emergency surveillance can guide preparations for future outbreaks of SARS or respiratory diseases of unknown etiology.