Preparing for biological threats: Addressing the needs of pregnant women.

Intentional release of infectious agents and biological weapons to cause illness and death has the potential to greatly impact pregnant women and their fetuses. We review what is known about the maternal and fetal effects of seven biological threats: Bacillus anthracis (anthrax); variola virus (smallpox); Clostridium botulinum toxin (botulism); Burkholderia mallei (glanders) and Burkholderia pseudomallei (melioidosis); Yersinia pestis (plague); Francisella tularensis (tularemia); and Rickettsia prowazekii (typhus). Evaluating the potential maternal, fetal, and infant consequences of an intentional release of an infectious agent requires an assessment of several key issues: (1) are pregnant women more susceptible to infection or illness compared to the general population?; (2) are pregnant women at increased risk for severe illness, morbidity, and mortality compared to the general population?; (3) does infection or illness during pregnancy place women, the fetus, or the infant at increased risk for adverse outcomes and how does this affect clinical management?; and (4) are the medical countermeasures recommended for the general population safe and effective during pregnancy? These issues help frame national guidance for the care of pregnant women during an intentional release of a biological threat. Birth Defects Research 109:391-398, 2017.© 2017 Wiley Periodicals, Inc.

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 Panelists discussed recent patients with systemic anthrax; reviews of published, unpublished, and proprietary data regarding antimicrobial drugs and anthrax antitoxins; and critical care measures of potential benefit to patients with anthrax.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.

Special considerations for prophylaxis for and treatment of anthrax in pregnant and postpartum women.

In August 2012, the Centers for Disease Control and Prevention, in partnership with the Association of Maternal and Child Health Programs, convened a meeting of national subject matter experts to review key clinical elements of anthrax prevention and treatment for pregnant, postpartum, and lactating (P/PP/L) women. National experts in infectious disease, obstetrics, maternal fetal medicine, neonatology, pediatrics, and pharmacy attended the meeting, as did representatives from professional organizations and national, federal, state, and local agencies. The meeting addressed general principles of prevention and treatment for P/PP/L women, vaccines, antimicrobial prophylaxis and treatment, clinical considerations and critical care issues, antitoxin, delivery concerns, infection control measures, and communication. The purpose of this meeting summary is to provide updated clinical information to health care providers and public health professionals caring for P/PP/L women in the setting of a bioterrorist event involving anthrax.

Prophylaxis and treatment of anthrax in pregnant women.

OBJECTIVE: To review the safety and pharmacokinetics of antimicrobials recommended for anthrax postexposure prophylaxis and treatment in pregnant women. DATA SOURCES: Articles were identified in the PubMed database from inception through December 2012 by searching the keywords (["pregnancy]" and [generic antibiotic drug name]). Additionally, we searched clinicaltrials.gov and conducted hand searches of references from REPROTOX, TERIS, review articles, and Briggs' Drugs in Pregnancy and Lactation. METHODS OF STUDY SELECTION: Articles included in the review contain primary data related to the safety and pharmacokinetics among pregnant women of 14 antimicrobials recommended for anthrax postexposure prophylaxis and treatment (amoxicillin, ampicillin, chloramphenicol, clindamycin, ciprofloxacin, doripenem, doxycycline, levofloxacin, linezolid, meropenem, moxifloxacin, penicillin, rifampin, and vancomycin). TABULATION, INTEGRATION, AND RESULTS: The PubMed search identified 3,850 articles for review. Reference hand searching yielded nine additional articles. In total, 112 articles met the inclusion criteria. CONCLUSIONS: Overall, safety and pharmacokinetic information is limited for these antimicrobials. Although small increases in risks for certain anomalies have been observed with some antimicrobials recommended for prophylaxis and treatment of anthrax, the absolute risk of these antimicrobials appears low. Given the high morbidity and mortality associated with anthrax, antimicrobials should be dosed appropriately to ensure that antibiotic levels can be achieved and sustained. Dosing adjustments may be necessary for the ß-lactam antimicrobials and the fluoroquinolones to achieve therapeutic levels in pregnant women. Data indicate that the ß-lactam antimicrobials, the fluoroquinolones, and, to a lesser extent, clindamycin enter the fetal compartment, an important consideration in the treatment of anthrax, because these antimicrobials may provide additional fetal benefit in the second and third trimesters of pregnancy.

Anthrax cases in pregnant and postpartum women: a systematic review.

OBJECTIVE: To describe the worldwide experience of Bacillus anthracis infection reported in pregnant, postpartum, and lactating women. DATA SOURCES: Studies were identified through MEDLINE, Web of Science, Embase, and Global Health databases from inception until May 2012. The key words (["anthrax" or "anthracis"] and ["pregna*" or "matern*" or "postpartum" or "puerperal" or "lact*" or "breastfed*" or "breastfeed*" or "fetal" or "fetus" or "neonate" or "newborn" or "abort*" or "uterus"]) were used. Additionally, all references from selected articles were reviewed, hand searches were conducted, and relevant authors were contacted. METHODS OF STUDY SELECTION: The inclusion criteria were: published articles referring to women diagnosed with an infection due to exposure to B anthracis during pregnancy, the postpartum period, or during lactation; any article type reporting patient-specific data; articles in any language; and nonduplicate cases. Non-English articles were professionally translated. Duplicate reports, unpublished reports, and review articles depicting previously identified cases were excluded. TABULATION, INTEGRATION, AND RESULTS: Two authors independently reviewed articles for inclusion. The primary search of the four databases yielded 1,340 articles, and the secondary crossreference search revealed 146 articles. Fourteen articles met the inclusion criteria. In total, 20 cases of B anthracis infection were found, 17 in pregnant women, two in postpartum women, and one case in a lactating woman. Among these reports, 16 women died and 12 fetal or neonatal losses were reported. Of these fatal cases, most predated the advent of antibiotics. CONCLUSIONS: Based on these case reports, B anthracis infection in pregnant and postpartum women is associated with high rates of maternal and fetal death. Evidence of possible maternal-fetal transmission of B anthracis infection was identified in early case reports.

Emerging and zoonotic infections in women.

Emerging infections, many zoonotic, are caused by a variety of pathogens with global distribution. Previously rare pathogens have emerged; global travel facilitates their rapid spread. Human encroachment on remote areas has brought contact with zoonotic diseases never before characterized. Although systematic study of rare outbreaks can be challenging, knowledge of emerging pathogens and their effects on women is accumulating. This article discusses effects of lymphocytic choriomeningitis virus, West Nile virus, severe acute respiratory syndrome coronavirus, avian influenza A virus, viral hemorrhagic fevers, spirochetal illnesses, and Chagas' disease. The potential impact of candidate bioterror agents and issues of prophylaxis and therapy are discussed.

A case of naturally acquired inhalation anthrax: clinical care and analyses of anti-protective antigen immunoglobulin G and lethal factor.

This report describes the first case of naturally acquired inhalation anthrax in the United States since 1976. The patient's clinical course included adjunctive treatment with human anthrax immunoglobulin. Clinical correlation of serologic assays for the lethal factor component of lethal toxin and anti-protective antigen immunoglobulin G are also presented.

Emerging infectious disease outbreaks: old lessons and new challenges for obstetrician-gynecologists.

OBJECTIVE: The purpose of this study was to summarize 3 recent high-profile infectious disease threats that have affected the United States: severe acute respiratory syndrome, West Nile virus, and anthrax. STUDY DESIGN: A systematic review was conducted with the use of Medline searches, searches of the Centers for Disease Control and Prevention website, and review by experts at the Centers for Disease Control and Prevention. RESULTS: The 3 emerging infectious diseases pose very different threats: Severe acute respiratory syndrome is a newly identified pathogen that caused an international pandemic; the West Nile virus investigation involved an old pathogen that was identified in a new location; and the anthrax attacks involved the intentional introduction of a pathogen. CONCLUSION: All 3 outbreaks highlight the importance of obstetrician-gynecologists keeping current with new information as it emerges. In this global environment, it is likely that novel disease threats will continue to emerge in the United States.

Emerging infections and pregnancy: West Nile virus, monkeypox, severe acute respiratory syndrome, and bioterrorism.

As new infectious diseases, such as West Nile virus, monkeypox, and severe acute respiratory syndrome (SARS) are recognized in the United States, there are critical questions about how these infectious diseases will affect pregnant women and their infants. In addition, the implications of bioterrorist attacks for exposed pregnant women need to be considered. In this article, the authors address the following questions for a number of infectious disease threats: (1) does pregnancy affect the clinical course of these novel infectious diseases?, (2) what are the implications for prophylaxis and treatment of exposed or infected pregnant women?, and (3) are these novel infectious diseases transmitted during pregnancy, labor and delivery, or breastfeeding?

The validity of chief complaint and discharge diagnosis in emergency department-based syndromic surveillance.

OBJECTIVE: Emergency department (ED)-based syndromic surveillance systems are being used by public health departments to monitor for outbreaks of infectious diseases, including bioterrorism; however, few systems have been validated. The authors evaluated a "drop-in" syndromic surveillance system by comparing syndrome categorization in the ED with chief complaints and ED discharge diagnoses from medical record review. METHODS: A surveillance form was completed for each ED visit at 15 participating Arizona hospitals between October 27 and November 18, 2001. Each patient visit was assigned one of ten clinical syndromes or "none." For six of 15 EDs, kappa statistics were used to compare syndrome agreement between surveillance forms and syndrome categorization with chief complaint and ED discharge diagnosis from medical record review. RESULTS: Overall, agreement between surveillance forms and ED discharge diagnoses (kappa = 0.55; 95% confidence interval [CI] = 0.52 to 0.59) was significantly higher than between surveillance forms and chief complaints (kappa = 0.48; 95% CI = 0.44 to 0.52). Agreement between chief complaints and ED discharge diagnoses was poor for respiratory tract infection with fever (kappa = 0.33; 95% CI = 0.27 to 0.39). Furthermore, pediatric chief complaints showed lower agreement for respiratory tract infection with fever when compared with adults (kappa = 0.34 [95% CI = 0.20 to 0.47] vs. kappa = 0.44 [95% CI = 0.28 to 0.59], respectively). CONCLUSIONS: In general, this syndromic surveillance system classified patients into appropriate syndrome categories with fair to good agreement compared with chief complaints and discharge diagnoses. The present findings suggest that use of ED discharge diagnoses, in addition to or instead of chief complaints, may increase surveillance validity for both automated and drop-in syndromic surveillance systems.

The role of the obstetrician-gynecologist in emerging infectious diseases: monkeypox and pregnancy.

Early in June 2003, the Centers for Disease Control and Prevention (CDC) announced yet another unique infectious disease outbreak, the first evidence of community-acquired monkeypox in the United States. By July 8, 2003, a total of 71 cases had been reported to CDC from 6 states. When emerging infectious diseases are reported in the United States, particularly when these reports receive widespread media attention, obstetrician-gynecologists may be called upon to rapidly respond to queries from their patients and to address certain infectious disease risks within their clinical practices. In addition, obstetrician-gynecologists may have specific concerns about the implications for an infectious disease outbreak, such as monkeypox, for pregnant women. Therefore, it is important that obstetrician-gynecologists know how to gather up-to-date and accurate information about infectious disease outbreaks and that they be familiar with the public health response system for responding to such outbreaks.

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.

Implementing syndromic surveillance: a practical guide informed by the early experience.

Syndromic surveillance refers to methods relying on detection of individual and population health indicators that are discernible before confirmed diagnoses are made. In particular, prior to the laboratory confirmation of an infectious disease, ill persons may exhibit behavioral patterns, symptoms, signs, or laboratory findings that can be tracked through a variety of data sources. Syndromic surveillance systems are being developed locally, regionally, and nationally. The efforts have been largely directed at facilitating the early detection of a covert bioterrorist attack, but the technology may also be useful for general public health, clinical medicine, quality improvement, patient safety, and research. This report, authored by developers and methodologists involved in the design and deployment of the first wave of syndromic surveillance systems, is intended to serve as a guide for informaticians, public health managers, and practitioners who are currently planning deployment of such systems in their regions.

World Trade Center rescue worker injury and illness surveillance, New York, 2001.

BACKGROUND: The September 11, 2001, terrorist attacks on the World Trade Center in New York City, New York, prompted an unprecedented rescue and recovery response. Operations were conducted around the clock, involved over 5000 workers per day, and extended into months following the attacks. The City of New York Department of Health and Mental Hygiene and the Centers for Disease Control and Prevention implemented prospective surveillance to characterize rescue worker-related injury and illness and to help guide public health interventions. METHODS: From September 11 to October 11, 2001, personnel reviewed medical records at four Manhattan hospital emergency departments (EDs), and healthcare providers completed data collection forms at five temporary Disaster Medical Assistance Team (DMAT) facilities located at the site. Rescue workers included construction workers, police officers, firefighters, emergency medical service technicians, or Urban Search and Rescue workers. Data collected included demographic characteristics, injury type, illness, and disposition. RESULTS: Of 5222 rescue worker visits, 89% were to DMAT facilities and 12% to EDs. Musculoskeletal conditions were the leading cause of visits (19%), followed by respiratory (16%) and eye (13%) disorders. Incidence rates were estimated based on total injuries and/or illnesses reported times 200,000 (100 equivalent full-time workers in 1 year at 40 hours per week x 50 weeks per year), then divided by the total number of hours worked. Eye disorders (59.7) accounted for the highest estimated injury and illness rate, followed by headache (46.8). One death, 52 hospital admissions, and 55 transports were reported. Findings underscored the need to coordinate distribution and enforcement of personal protective equipment use, purchase of diagnostic equipment to diagnose corneal abrasions, and distribution of health advisories. CONCLUSIONS: This system provided objective, timely information that helped guide public health interventions in the immediate aftermath of the attacks and during the prolonged rescue and recovery operations. Lessons learned can be used to guide future surveillance efforts.

The bioterrorism preparedness and response Early Aberration Reporting System (EARS).

Data from public health surveillance systems can provide meaningful measures of population risks for disease, disability, and death. Analysis and evaluation of these surveillance data help public health practitioners react to important health events in a timely manner both locally and nationally. Aberration detection methods allow the rapid assessment of changes in frequencies and rates of different health outcomes and the characterization of unusual trends or clusters. The Early Aberration Reporting System (EARS) of the Centers for Disease Control and Prevention allows the analysis of public health surveillance data using available aberration detection methods. The primary purpose of EARS is to provide national, state, and local health departments with several alternative aberration detection methods. EARS helps assist local and state health officials to focus limited resources on appropriate activities during epidemiological investigations of important public health events. Finally, EARS allows end users to select validated aberration detection methods and modify sensitivity and specificity thresholds to values considered to be of public health importance by local and state health departments.

Enhanced drop-in syndromic surveillance in New York City following September 11, 2001.

After the 2001 World Trade Center disaster, the New York City Department of Health was under heightened alert for bioterrorist attacks in the city. An emergency department (ED) syndromic surveillance system was implemented with the assistance of the Centers for Disease Control and Prevention to ensure early recognition of an increase or clustering of disease syndromes that might represent a disease outbreak, whether natural or intentional. The surveillance system was based on data collected 7 days a week at area EDs. Data collected were translated into syndromes, entered into an electronic database, and analyzed for aberrations in space and time within 24 hours. From September 14-27, personnel were stationed at 15 EDs on a 24-hour basis (first staffing period); from September 29-October 12, due to resource limitations, personnel were stationed at 12 EDs on an 18-hour basis (second staffing period). A standardized form was used to obtain demographic information and classify each patient visit into 12 syndrome categories. Seven of these represented early manifestations of bioterrorist agents. Data transfer and analysis for time and space clustering (alarms) by syndrome and age occurred daily. Retrospective analyses examined syndrome trends, differences in reporting between staffing periods, and the staff's experience during the project. A total of 67,536 reports were received. The system captured 83.9% of patient visits during the first staffing period, and 60.8% during the second staffing period (P < 0.01). Five syndromes each accounted for more than 1% of visits: trauma, asthma, gastrointestinal illness, upper/lower respiratory infection with fever, and anxiety. Citywide temporal alarms occurred eight times for three of the major bioterrorism-related syndromes. Spatial clustering alarms occurred 16 times by hospital location and 9 times by ZIP code for the same three syndromes. No outbreaks were detected. On-site staffing to facilitate data collection and entry, supported by daily analysis of ED visits, is a feasible short-term approach to syndromic surveillance during high-profile events. The resources required to operate such a system, however, cannot be sustained for the long term. This system was changed to an electronic-based ED syndromic system using triage log data that remains in operation.

Epidemiologic clues to bioterrorism.

Public health investigators have successfully carried out epidemiologic investigations of outbreaks of disease for many years. By far the majority of these outbreaks have occurred naturally. With the recent illnesses resulting from deliberate dissemination of B. anthracis on an unsuspecting population, public health investigation of diseases must now include consideration of bioterrorism as a potential cause of outbreaks of disease. The features of naturally occurring outbreaks have a certain amount of predictability in terms of consistency with previous occurrences, or at least biological plausibility. However, with a deliberately introduced outbreak or infection among a population, this predictability is minimized. In this paper, the authors propose some epidemiologic clues that highlight features of outbreaks that may be suggestive of bioterrorism. They also describe briefly the general process of involvement of agencies at various levels of government, public health and non-public health, depending on the extent of an outbreak or level of suspicion.

Investigation of Kawasaki syndrome risk factors in Colorado.

Risk factors for Kawasaki syndrome (KS) were evaluated through a case-control study during an investigation of a KS cluster in Denver, CO. KS was associated with a humidifier in the child's room (odds ratio, 7.3; 95% confidence interval, 1.8 to 29.3) and possibly with an antecedent respiratory illness. The use of humidifiers should be further investigated as part of future studies of KS.