Evidence Report/Technology Assessment 

Number 141 

Pediatric Anthrax: Implications for 

Bioterrorism Preparedness 

Prepared for: 

Agency for Healthcare Research and Quality 

U.S. Department of Health and Human Services 

540 Gaither Road 

Rockville, MD 20850 

www.ahrq.gov 

Contract No. 290-02-0017 

Prepared by: 

Stanford University—UCSF Evidence-based Practice Center, Stanford, CA 

Investigators 

Dena M. Bravata, M.D., M.S. 

Ewen Wang, M.D. 

Jon-Erik Holty, M.D., M.S. 

Robyn Lewis, M.A. 

Paul H. Wise, M.D., M.P.H. 

Smita Nayak, M.D. 

Hau Liu, M.D., M.B.A., M.P.H. 

Kathryn M. McDonald, M.M. 

Douglas K. Owens, M.D., M.S. 

AHRQ Publication No. 06-E013 

August 2006
This report is based on research conducted by the Stanford-UCSF Evidence-based Practice 

Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), 

Rockville, MD (Contract No. 290-02-0017). The findings and conclusions in this document are 

those of the authors who are responsible for its content; and do not necessarily represent the 

views of AHRQ. No statement in this report should be construed as an official position of the 

AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help clinicians, employers, policymakers, and 

others make informed decisions about the provision of health care services. This report is

intended as a reference and not as a substitute for clinical judgment. 

This report may be used, in whole or in part, as the basis for development of clinical practice 

guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage 

policies. AHRQ or U.S. Department of Health and Human Services endorsement of such 

derivative products may not be stated or implied. 
ii 

This document is in the public domain and may be used and reprinted without permission except 

those copyrighted materials noted for which further reproduction is prohibited without the 

specific permission of copyright holders. 

Suggested Citation: 

Bravata DM, Wang E, Holty J-E, Lewis R, Wise PH, Nayak S, Liu H, McDonald KM, Owens 

DK. Pediatric Anthrax: Implications for Bioterrorism Preparedness. Evidence 

Report/Technology Assessment No. 141. (Prepared by Stanford University—UCSF Evidencebased Practice Center under Contract No. 290-02-0017.) AHRQ Publication No. 06-E013. 

Rockville, MD: Agency for Healthcare Research and Quality. August 2006. 

The investigators have no relevant financial interests in the report. The investigators 

have no employment, consultancies, honoraria, or stock ownership or options, or 

royalties from any organization or entity with a financial interest or financial conflict 

with the subject matter discussed in the report. 
iii 

Preface 

 The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based 

Practice Centers (EPCs), sponsors the development of evidence reports and technology 

assessments to assist public- and private-sector organizations in their efforts to improve the 

quality of health care in the United States. This report was requested and funded by the Health 

Resources and Services Administration. The reports and assessments provide organizations with 

comprehensive, science-based information on common, costly medical conditions and new 

health care technologies. The EPCs systematically review the relevant scientific literature on 

topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to 

developing their reports and assessments. 

 To bring the broadest range of experts into the development of evidence reports and health 

technology assessments, AHRQ encourages the EPCs to form partnerships and enter into 

collaborations with other medical and research organizations. The EPCs work with these partner 

organizations to ensure that the evidence reports and technology assessments they produce will 

become building blocks for health care quality improvement projects throughout the Nation. The 

reports undergo peer review prior to their release. 

 AHRQ expects that the EPC evidence reports and technology assessments will inform 

individual health plans, providers, and purchasers as well as the health care system as a whole by 

providing important information to help improve health care quality. 

 We welcome comments on this evidence report. They may be sent by mail to the Task Order 

Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, 

Rockville, MD 20850, or by e-mail to epc@ahrq.gov. 

Carolyn M. Clancy, M.D. 

Director 

Agency for Healthcare Research and Quality 

Jean Slutsky, P.A., M.S.P.H. 

Director, Center for Outcomes and Evidence 

Agency for Healthcare Research and Quality 

Elizabeth M. Duke, Ph.D. 

Administrator 

Health Resources and Services Administration 

Beth A. Collins Sharp, Ph.D., R.N. 

Director, EPC Program 

Agency for Healthcare Research and Quality 

 Sally Phillips, Ph.D., R.N. 

Task Order Officer 

Agency for Healthcare Research and Quality 
iv

Acknowledgments

 We thank Emilee Wilhelm for her help with article retrieval and Corinna Haberland for her 

assistance with translations.
v

Structured Abstract 

Objectives. To systematically review the literature about children with anthrax to describe their 

clinical course, treatment responses, and the predictors of disease progression and mortality. 

Data Sources. MEDLINE® (1966-2005), 14 selected journal indexes (1900-1966) and 

bibliographies of all retrieved articles. 

Review Methods. We sought case reports of pediatric anthrax published between 1900 and 2005 

meeting predefined criteria. We abstracted three types of data from the English-language 

reports: (1) patient information (e.g., age, gender, nationality); (2) symptom and disease 

progression information (e.g., whether the patient developed meningitis); and (3) treatment 

information (e.g., treatments received, year of treatment). We compared the clinical symptoms 

and disease progression variables for the pediatric cases with data on adult anthrax cases 

reviewed previously. 

Results. We identified 246 titles of potentially relevant articles from our MEDLINE® search and 

2253 additional references from our manual search of the bibliographies of retrieved articles and 

the indexes of the 14 selected journals. We included 62 case reports of pediatric anthrax 

including two inhalational cases, 20 gastrointestinal cases, 37 cutaneous cases, and three atypical 

cases. Anthrax is a relatively common and historically well-recognized disease and yet rarely 

reported among children, suggesting the possibility of significant under-diagnosis, underreporting, and/or publication bias. Children with anthrax present with a wide range of clinical 

signs and symptoms, which differ somewhat from the presenting features of adults with anthrax. 

Like adults, children with gastrointestinal anthrax have two distinct clinical presentations: upper 

tract disease characterized by dysphagia and oropharyngeal findings and lower tract disease 

characterized by fever, abdominal pain, and nausea and vomiting. Additionally, children with 

inhalational disease may have “atypical” presentations including primary meningoencephalitis. 

Children with inhalational anthrax have abnormal chest roentgenograms; however, children with 

other forms of anthrax usually have normal roentgenograms. Nineteen of the 30 children (63%) 

who received penicillin-based antibiotics survived; whereas nine of 11 children (82%) who 

received anthrax antiserum survived. 

Conclusions. There is a broad spectrum of clinical signs and symptoms associated with 

pediatric anthrax. The limited data available regarding disease progression and treatment 

responses for children infected with anthrax suggest some differences from adult populations. 

Preparedness planning efforts should specifically address the needs of pediatric victims.

vii 

Contents 

Executive Summary..........................................................................................1 

Evidence Report..............................................................................................9

Chapter 1. Introduction......................................................................................11 

Key Research Questions............................................................................12 

Chapter 2. Methods...........................................................................................13 

Inclusion and Exclusion Criteria......... ....................................................... 13 

Search Strategy.......................................................................................14 

Data Abstraction and Evaluation..................................................................15 

Statistical Analysis...................................................................................16 

Peer Review Process.................................................................................16 

Chapter 3. Results.............................................................................................17 

 Summary of Included Studies.......................................................................17 

 Inhalational Anthrax.................................................................................18 

 Gastrointestinal Anthrax.............................................................................22 

 Cutaneous Anthrax....................................................................................27 

 Atypical Anthrax......................................................................................31 

Summary Analyses Including All Cases..........................................................35 

Summary Answers to the Key Questions..........................................................36 

Chapter 4. Discussion........................................................................................39 

 Limitations............................................................................................40 

 Future Research........................................................................................40 

 Conclusions............................................................................................41 

References......................................................................................................43 

Appendixes 

Appendix A: Data Abstracted 

Appendix B: Adult Anthrax Case Reports Not Included in this Analysis 

Appendix C: Peer Reviewers 

Appendixes and Evidence Tables for this report are provided electronically at 

http://www.ahrq.gov/clinic/tp/pedanthtp.htm. 

1 

Executive Summary 

Overview 

In response to the 2001 U.S. anthrax attack, there has been a proliferation of guidelines for 

the diagnosis and treatment of patients with anthrax. However, most of these have not specified 

screening and management protocols for specific populations, such as children. Efforts to 

prepare for and respond to future attacks of anthrax bioterrorism will be aided by detailed 

information about the clinical presentation and treatment responses of both adult and pediatric 

populations exposed to anthrax. 

We performed a systematic review of case reports of pediatric anthrax to describe the clinical 

course, treatment responses, and predictors of disease progression and mortality for children with 

anthrax infection. In addition to cases of inhalational, gastrointestinal, and cutaneous anthrax, 

we included in our analysis case reports of primary anthrax meningoencephalitis (without an 

identifiable inhalational, gastrointestinal, or cutaneous source). 

Key Questions 

We sought to synthesize the data from English-language case reports of children with anthrax 

to answer three key research questions: 

1. What is the evidence for an age-dependent clinical course associated with anthrax? 

2. How effective are antibiotic prophylaxis and treatment for anthrax in children compared 

to adults? Similarly, how effective are other medical treatments in children compared to 

adults (e.g. ventilator/respiratory support)? 

3. Based on the review of evidence for Questions 1 and 2, what are the implications for 

children versus adults in terms of preparedness and response planning for anthrax 

exposure (i.e., healthcare provider education on diagnosis and management, 

considerations for hospitals, vaccination strategies)? 

Methodology 

We sought English-language case reports of patients aged 18 years or younger with 

confirmed inhalational, gastrointestinal, or atypical anthrax (e.g., primary anthrax 

meningoencephalitis without an identifiable inhalational or cutaneous source). Because there 

have been hundreds of case reports of pediatric cutaneous anthrax, we selected a random sample 
2 

of 50 English-language case reports of pediatric cutaneous anthrax for abstraction. We then 

augmented the data abstracted from the English-language pediatric case reports with the data 

available from our prior Evidence Report on adult cases of inhalational anthrax. Given key 

physiological differences among infants, toddlers, and adolescents, we analyzed case reports in 

three age groups: 0 to 2 years, >2 to 13 years, and >13 to 18 years. 

We identified case reports of pediatric anthrax referenced in MEDLINE® between January 

1966 and June 2005 using the MeSH terms anthrax and case report. We then performed 

additional comprehensive searches of retrieved bibliographies and the indexes of selected 

journals from 1900 to 1966 (e.g., New England Journal of Medicine, JAMA, Lancet, Medical 

Journal of Australia, La Presse Médicale, Deutsche Medizinische Wochenschrift, La Semana 

Medicale). We also performed extensive manual searches of retrieved bibliographies. 

Two investigators screened potentially relevant articles to determine whether they met 

inclusion criteria. One investigator independently abstracted patient data from each included case 

report and reviewed bibliographies for additional potentially relevant studies. Because the 

purpose of this project was to characterize the spectrum of pediatric anthrax disease as well as to 

identify the differences in disease progression and treatment responses of adults and children 

with anthrax, we abstracted three primary types of data from each included article: (1) patient 

information (e.g., age, gender); (2) symptom and clinical course information (e.g., whether the 

patient developed meningitis); and (3) treatment information. 

We performed univariate analyses to summarize the key patient and treatment characteristics. 

We applied a Bonferroni correction to account for multiple comparisons. 

Findings 

We identified 246 titles of potentially relevant articles from our MEDLINE® search and 2253 

additional references from our manual search of the bibliographies of retrieved articles and the 

indexes of the 14 selected journals. We identified 62 case reports of pediatric anthrax including 

two inhalational cases, 20 gastrointestinal cases, 37 cutaneous cases, and three atypical cases. 

Most of the included cases were of adolescents: we found seven cases of children aged 0 to 2 

years old, 22 cases of children more than 2 years to 13 years old, and 34 cases of adolescents 

aged more than 13 years to 18 years old. We did not find any reports of anthrax in pregnant 

women or reports of prenatal cases of anthrax. 

Among the 59 case reports which stated the patient’s gender, only 14 (24%) were girls. This 

is similar to the gender discrepancy observed among adults. Several plausible explanations for 

this gender disparity include that anthrax has largely been an occupational disease among 

professions traditionally dominated by men and boys (e.g., woolsorters and butchers) and that 

there may be biases that result in the under-diagnosis and under-reporting of girls with anthrax. 

Overall, the mortality rate was 31%. Among patients who received antibiotics, 71% survived 

compared to 82% of patients who received antiserum. Only one patient was treated with a 

fluroquinolone—a key component of the current treatment guidelines for anthrax. None of the 

included patients received anthrax vaccine. 
3 

Pediatric Inhalational Anthrax 

Inhalational anthrax occurs when anthrax spores are inhaled into the lung. There is 

insufficient evidence available from the two English- and three foreign-language case reports of 

pediatric anthrax to classify the typical presentation of inhalational anthrax or treatment 

responses or to compare them to adults with inhalational disease. In particular, we have very 

little information about inhalational anthrax in infants or toddlers. However, the evidence that is 

available on pediatric inhalation anthrax does provide us with four key observations. 

• Among adults, inhalational anthrax presents with a prodromal phase (often described as 

flu-like) for whom the most common symptoms or findings at admission are abnormal 

temperature, abnormal lung findings, fever or chills, tachycardia, fatigue or malaise, 

cough, dyspnea, and nausea or vomiting. Notably, these symptoms are typically 

accompanied by nonheadache neurological symptoms such as dizziness, visual changes, 

and syncope, which are not typical of routine influenza infection. The three children for 

whom we have signs and symptom data were found to have dyspnea and abnormal lung 

exams; however, none had either nonheadache neurological symptoms or nausea or 

vomiting. This suggests that screening algorithms based on adult findings may have less 

diagnostic accuracy for children presenting with inhalational anthrax. 

• Adult patients typically have abnormal chest roentgenograms characterized by pleural 

effusions or widened mediastinum. Both of the pediatric patients with inhalational 

anthrax who had chest roentgenograms were found to have similar abnormalities. 

• Prior to the introduction of antibiotics, anthrax infection was primarily treated with antiserum, which reportedly decreased mortality by 75% compared to untreated patients. 

Later, effective antibiotics such as penicillin and chloramphenicol were added to anthrax 

treatment strategies. Current treatment guidelines for inhalational in children vary among 

different professional organizations; however, most recommend triple intravenous 

antibiotics with ciprofloxacin or doxycycline with two other antibiotics such as 

clindamycin, rifampin, penicillin, among others. Among adult patients, nearly all of those 

not given antibiotics or anthrax anti-serum during the prodromal phase progress to the 

fulminant phase which is a characterized by a rapidly progressive critical illness with 

respiratory failure, shock. Regardless of antibiotic/anti-serum therapy or other medical 

intervention such as mechanical ventilation, the overall mortality rate in fulminant phase 

is 97%. Similarly, the child who received antibiotic treatment during the fulminant phase 

died. The two children who survived inhalational anthrax were treated with antiserum—a 

treatment not typically included in current treatment guidelines or bioterrorism 

preparedness inventories. 

• In adults, pleural fluid drainage has been significantly associated with survival after the 

development of fulminant inhalational anthrax. Only one child with inhalational anthrax 

received pleural fluid drainage and she survived. 
4 

Pediatric Gastrointestinal Anthrax 

Gastrointestinal anthrax results from the ingestion of B. anthracis spores leading to the 

infection (and often ulceration) of the gastrointestinal epithelium. We found 20 English-language 

case reports of pediatric gastrointestinal anthrax—most of them were associated with known 

outbreaks, typically resulting from the consumption of contaminated meat. The average age of 

these patients was 10.5 years (four children were < 2 years old, eight children were >2 to 13 

years old; and eight children were >13 to 18 years old). Five were girls and none of the cases 

were from the U.S. The literature on pediatric gastrointestinal anthrax provides four key results. 

• Compared to inhalational and cutaneous disease, gastrointestingal anthrax is considered 

quite rare among adults, especially in the U.S. However, among children, there have been 

more case reports of gastrointestinal disease than inhalational disease. Clearly, children 

are susceptible to gastrointestinal anthrax from agricultural sources—whether they would 

be more or less likely to present with primary gastrointestinal disease after a bioterrorism 

event is not known. 

• Historically, gastrointestinal anthrax has been recognized as presenting in two forms: 

oropharyngeal disease among patients in whom the site of infection is the upper 

gastrointestinal tract and intestinal disease among patients in whom the site of infection is 

the lower gastrointestinal tract. Like adults, children seem to have two presentations of 

gastrointestinal anthrax: upper tract disease characterized by dysphagia and 

oropharyngeal findings and lower tract disease characterized by fever, abdominal pain, 

and nausea and vomiting. 

• Of the four patients with gastrointestinal anthrax who had roentgenograms, two were 

found to have pulmonary abnormalities, one patient had “ascites but no other 

abnormalities,” and one had a normal examination. From the limited evidence, we 

cannot determine whether roentgenograms contributed significantly to the early diagnosis 

of pediatric gastrointestinal anthrax. 

• The mortality rate for treated gastrointestinal anthrax among adults is generally reported 

as approximately 40%. However, the children with gastrointestinal anthrax (both treated 

and untreated) had a somewhat higher case-fatality rate (63%). Among the children with 

gastrointestinal disease who died, many had developed meningoencephalitis, presumably 

as a result of hematologic dissemination. 

Pediatric Cutaneous Anthrax 

Cutaneous anthrax has long been recognized as an occupational hazard for adults handling 

contaminated animal products who introduce B. anthracis spores into the skin through cuts, 

abrasions, or insect bites. It is reported to account for more than 95% of clinical anthrax disease. 

We randomly selected 50 English-language case reports of children with cutaneous anthrax. Of 

these, only 37 provided sufficient information about individual patients to be included in our 
5 

analysis. In general, even the included reports of pediatric cutaneous anthrax were of very poor 

quality, often providing only a few sentences about the patient and their clinical course (and 

rarely even describing the skin lesions in detail). The reports of these 37 children with cutaneous 

anthrax provide three key findings. 

• Historically, cutaneous anthrax usually begins with a small, painless, pruritic papule on 

an exposed area. This lesion enlarges and becomes an oval eschar surrounded by vesicles 

with marked, painless brawny edema and tissue necrosis. The skin lesions described for 

children are similar to the classical skin lesions described for adults. 

• Only seven of the included pediatric cutaneous cases were girls (the gender was 

unreported for three cases). This male predominance is similar to what has been 

observed among adults and may represent the relatively higher risk of occupational 

exposures among boys and men or under-diagnosis or under-treatment of girls with 

anthrax. 

• Among adults, untreated cutaneous anthrax has been associated with a 5 to 20% case 

fatality rate (presumably from hematologic dissemination of disease) but is rarely fatal 

when treated. Only five children died (13.5% case fatality rate) which falls within the 

range of adult case fatality rates. All of these were boys, three of whom had not received 

antibiotics. One child developed meningoencephalitis before he died. 

Atypical Anthrax 

Historically, anthrax has been classified according to the three principal exposures: 

inhalational, gastrointestinal, and cutaneous. Although rare, atypical anthrax presentations do 

occur among adults including laryngopharyneal and nasopharyngeal disease and primary anthrax 

meningoencephalitis. Some authors have speculated that the port of entry for primary anthrax 

meningoencephalitis is either an unrecognized lower respiratory tract port of entry or 

transethmoid migration of occult nasopharyngeal infection. 

We found 2 cases of pediatric laryngopharyngeal anthrax, one report of a girl with 

nasopharyngeal disease, and one English-language and five foreign language case reports of 

children with primary meningoencephalitis (97% of whom died). From these cases, we conclude, 

that, although uncommon, children can have atypical presentations of anthrax. Although we 

cannot determine with certainty the means by which these patients contracted anthrax, we 

suspect an inhalational exposure for many, if not most, of them. To prevent delays in diagnosis 

and therapy during future bioterrorist attacks, clinicians should recognize that anthrax infection 

in both adults and children might present with primary nasal, laryngeal, pharyngeal, and/or 

meningeal symptoms. 

 
6 

Discussion and Summary Answers to the Key Questions 

Anthrax is a relatively common and historically well-recognized disease and yet rarely 

reported among children—particularly among the very young children. The paucity of pediatric 

anthrax case reports, particularly among the youngest children, suggests that these children may 

have less exposure to anthrax or that anthrax infection in this population may be under-diagnosed 

and/or under-reported. We note that the presenting symptoms for pediatric inhalational anthrax 

are very common for many childhood diseases and that naturally occurring anthrax disease is 

most prevalent in poor countries where children may never come to medical attention or have 

diagnostic cultures confirmed. Additionally, there may be a significant publication bias in this 

literature (e.g., cases that are unusual or fatal may be more likely to be published).. 

Key Question #1: What Is the Evidence for an Age-dependent Disease 

Progression Associated with Anthrax? 

Although children with anthrax may present with somewhat different symptoms than adults, 

we found no specific evidence for age-dependent differences in disease progression. Like adults, 

children with gastrointestinal anthrax, seem to have two distinct clinical presentations: One 

resulting from upper tract disease and another resulting from lower tract disease. Additionally, 

children with inhalational disease may have non-pulmonary presentations including primary 

meningoencephalitis. 

Key Question #2: How Effective Are Antibiotic Prophylaxis and 

Treatment for Anthrax in Children Compared to Adults? Similarly, 

how effective are other medical treatments in children compared to 

adults (e.g. ventilator/respiratory support)? 

Most of the children included in our analysis who received an antibiotic were given 

penicillin-based antibiotics which produced a 63% survival rate. Other successful treatments 

included antiserum, which produced an 82% survival rate. These survival rates were similar to 

those observed for adults. 

In adults, pleural fluid drainage was significantly associated with survival after the 

development of fulminant inhalational anthrax. One child with inhalational anthrax received 

pleural fluid drainage and she survived. However, we found insufficient cases of children who 

received pleural fluid drainage (or other treatment modalities such at mechanical ventilation) to 

determine the extent which they may be more or less effective in children than they are in adults. 
7 

Key Question #3: Based on the review of evidence for Questions 1 

and 2, what are the implications for children versus adults in terms of 

preparedness and response planning for anthrax exposure (i.e., 

healthcare provider education on diagnosis and management, 

considerations for hospitals, vaccination strategies)? 

The results of our systematic review have implications for preparedness planning efforts that 

relate to the diagnosis and management of children with anthrax. The presenting signs and 

symptoms of children with anthrax are very similar to the signs and symptoms of children 

presenting with much more common infectious diseases. This creates a difficult diagnostic 

challenge both for clinicians needing to make a timely diagnosis and public health officials 

implementing syndromic surveillance systems. More research is needed to identify the specific 

signs and symptoms that distinguish common pediatric infections such as influenza from early 

anthrax infection. 

Only one of the 62 pediatric anthrax cases was treated with a fluoroquinolone; however, 

penicillin-based and antiserum regimens were much more commonly used among the included 

cases and were associated with favorable survival rates. Antiserum is not included in current 

treatment guidelines or bioterrorism preparedness inventories and has been associated with 

serum sickness and inconsistency in effectiveness across batches. Similarly, current treatment 

guidelines do not include penicillin as a single agent due to concerns of penicillin-resistant 

organisms. Thus, we have little evidence about the use of the medical regimens currently 

considered first line against anthrax and more evidence about those therapies not currently being 

recommended 

. 

Future Research 

To facilitate accurate diagnosis and effective treatment of children with anthrax, future 

pediatric anthrax case reports should provide much more detailed information about exposure, 

clinical presentation, and treatment responses for infants, toddlers, and adolescents with anthrax. 

The finding that anthrax antiserum was associated with survival among historical cases of 

children with anthrax warrants additional research on the safety, efficacy, and potential 

availability of this therapy. Similarly, we found no reports of children having received anthrax 

vaccine (which is currently only available for adults)—additional research is required regarding 

the safety and effectiveness of anthrax vaccination for both prophylaxis and treatment of children 

exposed to anthrax. 

The finding that children may not present with the same signs and symptoms as adults has 

implications for syndromic surveillance systems (e.g., the finding that non-headache 

neurological symptoms was a key distinguishing feature of adult inhalational anthrax was not 

found among children). Specifically, the development of pediatric syndromic surveillance 

requires additional research to identify the key presenting signs and symptoms of pediatric 

anthrax that distinguish patients with this disease from other common infections. 

 


Evidence Report

11 

Chapter 1. Introduction 

 Ring-a-ring-a-roses 

 A pocket full of posies 

 A-tishoo! A-tishoo! 

We all fall down.1

In response to the intentional release of Bacillus anthracis by mail in 2001, there has been a 

proliferation of guidelines for the diagnosis and treatment of patients with anthrax.2-10 However, 

most of these have not specified screening and management protocols for special populations, 

such as children. Children will likely be among the victims of future bioterrorism attacks on the 

general public as they were during the 1995 sarin attack in Tokyo (which affected 16 children 

and five pregnant women) and the 1984 intentional Salmonella contamination of salad bars in 

Oregon (which affected numerous high school students).1

 Additionally, children may be the 

specific targets of some terrorists as they were during the unsuccessful 1995 plot to release a 

chlorine gas bomb in California’s Disneyland.11 There is not a clear consensus as to whether 

children have particular physiological vulnerabilities to biological threat agents; however, young 

children may not be capable of seeking medical care or following the instructions of clinicians or 

public health officials—this can be particularly problematic if their parents or caregivers have, 

themselves, been incapacitated.1, 11-13 Efforts to prepare for and respond to future attacks of 

anthrax bioterrorism will be aided by detailed information about the clinical presentation and 

treatment responses of both adult and pediatric populations exposed to anthrax. 

Principally because of the paucity of pediatric cases in large case series of anthrax, observers 

have speculated that children are less susceptible to anthrax infection and may have different 

clinical courses after infection than adults. For example, during the 1979 Sverdlovsk outbreak, 

70 patients were exposed and developed clinical anthrax after an airborne release of spores.14, 15 

However, there were no victims under the age of 24 reported—despite the fact that children were 

in the path of the plume.16 Additionally, researchers have noted that there was no age-dependent 

susceptibility noted among the Sverdlovsk victims above 24 years of age.16 However, because 

there are no published reports synthesizing data from all reported pediatric cases of anthrax, it is 

unknown to what extent patient characteristics, early detection, and early treatment affect disease 

progression and mortality in pediatric populations. 

The development of protocols for the screening of pediatric patients with suspected anthrax 

and their subsequent management should be based on evaluation of the available literature 

regarding the clinical presentation and disease progression of children exposed to anthrax. Thus, 

we performed a systematic review of case reports of pediatric anthrax to describe the clinical 

course, treatment responses, and predictors of disease progression and mortality for children with 

 

1

 This nursery rhyme has been attributed to the pandemic of bubonic plague of the 1340s. Specifically, the ring-a-roses refers to 

the rose-colored rash of plague and the posies refer to the flowers and spices put into the pockets of victims to ward off the stench 

of death. The last two lines refer to the sneezing that was common among the victims just before their seemingly inevitable 

deaths. 
12 

anthrax infection. In addition to cases of inhalational, gastrointestinal, and cutaneous anthrax, 

we included in our analysis case reports of primary anthrax meningoencephalitis (i.e., without an 

identifiable inhalational, gastrointestinal, or cutaneous source). 

Key Research Questions 

For a previous evidence report, “Regionalization of Bioterrorism Preparedness and 

Response”17 we synthesized all cases of adult inhalational anthrax published between 1900 and 

2005. For the current project, we sought to synthesize the data from English-language case 

reports of children with inhalational, gastrointestinal, cutaneous, and atypical anthrax to answer 

three key research questions: 

1. What is the evidence for an age-dependent clinical course associated with anthrax? 

2. How effective are antibiotic prophylaxis and treatment for anthrax in children compared 

to adults? Similarly, how effective are other medical treatments in children compared to 

adults (e.g. ventilator/respiratory support)? 

3. Based on the review of evidence for Questions 1 and 2, what are the implications for 

children versus adults in terms of preparedness and response planning for anthrax 

exposure (i.e., healthcare provider education on diagnosis and management, 

considerations for hospitals, vaccination strategies)? 
13 

Chapter 2. Methods 

We sought all English-language case reports of patients aged 18 years or younger with 

inhalational, gastrointestinal, or atypical anthrax (e.g., primary anthrax meningoencephalitis 

without an identifiable inhalational or cutaneous source). Because there have been hundreds of 

case reports of pediatric cutaneous anthrax, given limited resources, we selected a random 

sample of 50 English-language case reports of pediatric anthrax for abstraction. We then 

augmented the data abstracted from the English-language pediatric case reports with the data 

available from our prior Evidence Report on adult cases of inhalational anthrax.17 

Inclusion and Exclusion Criteria 

We considered articles eligible for inclusion if the authors of the case report established a 

definitive diagnosis of anthrax. To confirm the diagnosis of anthrax, we used the case criteria 

that we developed previously which require that patients have positive cultures, gram stain, or 

immunologic evidence of recent Bacillus anthracis infection and/or associated clinical or 

autopsy findings consistent with anthrax infection.17 We present our overall inclusion strategy in 

Figure 1 and our separate inclusion criteria for inhalational anthrax in Table 1, gastrointestinal 

anthrax in Table 2, cutaneous anthrax in Table 3, primary anthrax meningoencephalitis in Table 

4, and atypical anthrax in Table 5. If the authors of a case report described a patient as having a 

particular type of anthrax (such as gastrointestinal disease) and they did not meet our inclusion 

criteria for that type of anthrax, we noted this. We excluded reports in which the authors 

presented summary information about a group of patients with anthrax but did not include 

individual patient data. 

Figure 1. Inclusion strategy 

Step 1: Identify all published case reports of patients with confirmed anthrax infection. 

Step 2: Identify patients

with signs, symptoms, or 

autopsy findings typical 

of inhalational anthrax.

Step 5. Identify patients

with evidence of anthrax 

meningoencephalitis

who have not been 

previously classified as 

having inhalational, 

gastrointestinal, or 

cutaneous anthrax.

Step 3: Identify patients

with history of 

contaminated meat 

consumption, clinical 

signs, symptoms, or 

autopsy findings 

consistent with a 

gastrointestinal anthrax.

Step 6. Identify all other 

patients with confirmed 

anthrax infection who do 

not have inhalational, 

gastrointestinal, or 

cutaneous anthrax or 

primary anthrax 

meningitis. These 

patients are considered to 

have atypical anthrax

infection.

Step 4: Identify patients

with lesions consistent 

with cutaneous anthrax.
14 

Table 1. Inclusion criteria for cases with presumed inhalational anthrax 

Any one of the following: 

1. Culturesa

 AND symptomsb or autopsy findingsc consistent with inhalational anthrax.

2. Symptoms and gram-stain evidenced

 AND improvement with appropriate therapy or autopsy findings. 

3. During an ongoing anthrax outbreak with confirmed cases (meeting criteria 1 or 2): 

 Symptoms AND autopsy findings or improvement with appropriate therapy.e

4. For patients with high-risk inhalational anthrax exposure (e.g., wool mill worker) who did not receive antibiotic 

treatment: Symptoms AND improvement with anthrax antiserum. 

 

Table 2. Inclusion criteria for cases with presumed gastrointestinal anthrax 

Any one of the following (exclude if patient meets cutaneous or inhalational case definition): 

1. Symptomsf

 AND cultures or gram-stain AND history of contaminated meat consumption or during outbreak of 

gastrointestinal anthrax. 

2. History of contaminated meat consumption or cases occurred during an ongoing gastrointestinal anthrax outbreak 

with confirmed cases (meeting criteria 1) AND Autopsy findingsg or symptoms with improvement with appropriate 

therapy. 

Table 3. Inclusion criteria for cases with presumed cutaneous anthrax 

Any one of the following (exclude if patient meets inhalational case definition): 

1. Cultures AND any skin lesion 

2. Skin lesion and gram-staind

 AND improvement with appropriate therapy 

3. During an ongoing anthrax outbreak with confirmed cases (meeting criteria 1 or 2): skin lesions AND improvement 

with appropriate therapy 

4. For patients with high-risk inhalational anthrax exposure (e.g. wool mill worker) who did not receive antibiotic 

treatment: skin lesions AND improvement with anthrax antiserum. 

Table 4. Inclusion criteria for cases with presumed primary anthrax meningoencephalitis 

The following (exclude if patient meets inhalational, gastrointestinal, or cutaneous case definitions): 

Culture or gram-stain AND either cerebrospinal fluidh

 or autopsyi findings consistent with anthrax 

meningoencephalitis.

 Table 5. Inclusion criteria for cases with presumed atypical anthrax 

The following (exclude if patient meets inhalational, gastrointestinal, cutaneous, or primary anthrax meningitis case 

definitions): 

Culture or gram-stain or autopsyi

 findings consistent with anthrax. a

Culture (any source) or immunological evidence of recent Bacillus anthracis infection. b

Clinical symptoms of inhalational anthrax included flu like symptoms, fever, cough, dyspnea, chest pain, abnormal lung exam, or

mediastinal widening or pleural effusions on chest roentenogram. c

Autopsy findings of inhalational anthrax included excessive pleural fluid (particularly if hemorrhagic), enlarged or hemorrhagic 

mediastinum, mediastinal lymphadenopathy, or subpleural congestion.14, 18, 19

d

Gram-stain evidence (any source) of B. anthracis: gram-positive, spore-forming, nonmotile, hemolytic, spore-forming bacilli measuring 

1-1.3 x 3-10 μm.20

e

Received appropriate antibiotics (% B. anthracis strains susceptible ≥70%) or anti-serum. f

Clinical symptoms of gastrointestinal anthrax included diarrhea (especially bloody/tarry), abdominal pain, abdominal distension and/or 

evidence of ascites. g

Autopsy findings of gastrointestinal anthrax included excessive peritoneal fluid (particularly if hemorrhagic), enlarged or hemorrhagic 

mesenteric lymphadenopathy, and/or small bowel/stomach ulceration(s). h

Cerebral spinal fluid consistent with meningoencephalitis (e.g., bloody fluid, leukocytosis, etc.) i

Autopsy findings consistent with meningoencephalitis (e.g., hemorrhagic meninges). 
15 

Search Strategy 

We identified case reports of pediatric anthrax referenced in MEDLINE® between January 

1966 and June 2005 using the MeSH terms anthrax and case report. We then performed 

additional comprehensive searches of retrieved bibliographies and the indexes of the following 

selected journals from 1900 to 1966: New England Journal of Medicine, JAMA, AMA-Archives 

of Internal Medicine, Lancet, BMJ, Medical Journal of Australia, La Presse Médicale, Bulletins 

et Mémoires de la Société Médicale des Hôpitaux de Paris, Deutsche Medizinische 

Wochenschrift, Wiener Medizinische Wochesnschrift, Wiener Klinische Wochenschrift, 

Muenchener Medizinische Wochenschrift, Berliner Klinische Wochenschrift, La Semana 

Medicale. From our previous synthesis of adult inhalational anthrax cases, we found that much 

of the literature on clinical anthrax was published before 1966 (the earliest publication 

referenced in MEDLINE®). Thus, we performed extensive manual searches of retrieved 

bibliographies. 

Because case reports of pediatric inhalational anthrax are relatively rare, in an effort to 

maximize the number of included cases, we included case reports of pediatric anthrax (0 to 18 

years of age) presenting from 1900 to 2005. Although medical treatment for anthrax has 

changed considerably since 1900 (particularly since the advent of effective antimicrobials), we 

were interested in presenting signs and symptoms, which would not be affected by medical 

interventions. We excluded articles that described cases presenting prior to 1900 because B. 

anthracis was not identified as the causative agent of clinical inhalational anthrax until 187721

and because the use of reliable microscopic22 and cultural examination techniques23 to confirm 

the diagnosis were not developed until the late 19th century. 

 

Data Abstraction and Evaluation 

Two investigators screened potentially relevant articles to determine whether they met 

inclusion criteria. One investigator independently abstracted patient data from each included 

English language article and reviewed bibliographies for additional potentially relevant studies. 

We resolved abstraction discrepancies by repeated review and discussion. If two or more studies 

presented the same data from a single patient, we included the data only once in our analyses. 

Because the purpose of this project is to characterize the spectrum of pediatric anthrax 

disease as well as to identify the differences in disease progression and treatment responses of 

adults and children with anthrax, we abstracted three primary types of data from each included 

article: (1) patient information (e.g., age, gender, nationality); (2) symptom and disease 

progression information (e.g., whether the patient developed meningitis); and (3) treatment 

information (e.g., treatments received, year of treatment). Data abstractions were performed 

directly into a detailed Excel abstraction form. The abstracted variables and their brief definitions 

are provided in Appendix A (including the definitions of some of the medical terms used in the 

case descriptions of individual patients). 
16 

To obtain a random sample of 50 case reports of pediatric cutaneous anthrax, we used a 

random number generator to select 50 reference identification numbers from the more than 200 

pediatric cutaneous case reports that we retrieved from our literature search. 

To evaluate the quality of the included case reports, we determined the extent to which the 

diagnosis of anthrax was confirmed (e.g., autopsy versus cultures versus response to therapy 

during a known outbreak) and whether the source of infection (e.g., inhalational disease) was 

established. 

Statistical Analysis 

Given key physiological differences among infants, toddlers, and adolescents, we analyzed 

case reports according to three age groups: 0-2 years, 3-13 years, and 14-18 years. Univariate 

analyses enabled us to summarize the key patient and treatment characteristics. We computed 

correlation coefficients between mortality and patient and treatment factors. For single 

comparisons, we considered a p-value less than 0.05 statistically significant. When comparing 

U.S 2001 to pre-2001 cases (or patients who lived to those who died), we applied a Bonferroni 

correction to account for multiple comparisons (we considered a p-value less than 0.025 

statistically significant (0.05/2 = 0.025)). 

Peer Review Process 

A draft of this Evidence Report was sent to a panel of seven experts in pediatrics, infectious 

diseases, public health, and bioterrorism preparedness (Appendix C). Their comments were 

incorporated into the final Report. 
17 

Chapter 3. Results 

Summary of Included Studies 

We identified 246 titles of potentially relevant articles from our MEDLINE® search and 2253 

additional references from our manual search of the bibliographies of retrieved articles and the 

indexes of the 14 selected journals. After removing duplicate reports, we included 62 English 

case reports of pediatric anthrax from which we abstracted detailed patient, treatment, and 

disease progression information. We did not find any reports of anthrax in pregnant women or 

reports of prenatal cases of anthrax. 

Table 6 describes the distribution of these cases by source of anthrax infection and compares 

them to the non-English language case reports and adult case reports for which we have limited 

data (previously collected). 

Table 6. Distribution of anthrax case reports by source, language, and age 

Source of Anthrax Infection Number of Pediatric Cases Number of Adult Cases 

English NonEnglish Total English NonEnglish Total 

Inhalational 2 3 5 45 32 77 

Gastrointestinal 20 2 22 42 50 92 

Cutaneous 222b

 229 451 895 1724 2619 

Atypical: Laryngopharyngeal 2 0 2 0 2 2 

Atypical: Nasopharyngeal 0 1 1 2 3 5 

Atypical: Primary Meningoencephalitis 1 5 6 22 10 32 

a

Pediatric Cases were defined as those in persons ≤ 18 years old. b

Of the 222 cutaneous cases, we selected a random sample of 50 for abstraction, of which only 37 provided sufficient data for 

inclusion in this analysis. 

 Given key physiological differences among infants, toddlers, and adolescents, we analyzed 

the English-language case reports according to three age groups: 0 to 2 years old (7 cases), more 

than 2 years to 13 years old (22 cases), and more than 13 years to 18 years old (34 cases) (Table 

7). We found relatively few English-language case reports of infants and young children with 

anthrax. This paucity of case reports among the youngest children result from several factors. 

First, anthrax has been historically recognized as an occupational disease so it is reasonable that 

only older children would have these occupational exposures. Additionally, particularly because 

the presenting signs and symptoms of anthrax-related disease are similar to other infectious 

diseases, there may be biases resulting in under-diagnosis and under-reporting of anthrax among 

the youngest children. 
18 

Table 7. Distribution of English-language cases by age 

Age Group Source of Anthrax Infection Number of 

Cases 

Number of 

Females Number Surviving 

0 to 2 years Inhalational 0 0 N/A 

Gastrointestinal 4 2 (50%) 1 (25%) 

 Cutaneous 3 2 (66.7%) 1 (33%) 

 Atypical 0 0 N/A 

Inhalational 1a

 1 (100%) 1 (50%) 

Gastrointestinal 8 1 (12.5%) 3 (42.8%)b

Cutaneous 12 1 (8%) 12 (100%) 

>2 to 13 years 

Atypical: Laryngopharyngeal 1 0 (0%) 1 (100%) 

Inhalational 1 1 (100%) 0 

Gastrointestinal 8 2 (25%) 3 (37.5%) 

Cutaneous 22 4 (21%)c

 18 (82%) 

>13 to 18 

years 

Atypical: Laryngopharyngeal 1 0 (0%) 1 (100%) 

 Atypical: Primary Meningoencephalitis 1 0 (0%) 0 (0%) 

a

This cases was 2.5 years old. 

b

One case report of gastrointestinal anthrax did not state if the patient survived. 

c

Three reports of patients with cutaneous anthrax did not state the patients’ gender. 

N/A = not applicable 

In the sections that follow, we first present the results for each types of pediatric anthrax 

(e.g., inhalational, gastrointestinal) then present summary information about all reviewed cases 

including summary information about treatment responses. 

Inhalational Anthrax 

Background. Because it is assumed that during a bioterrorism event, anthrax spores would 

be inhaled from an aerosolized source, a comprehensive assessment of the clinical presentation 

of inhalational anthrax is essential for early diagnosis. We direct interested readers elsewhere for 

reviews of the adult literature of inhalational anthrax.24, 25 Briefly, among adults inhalational 

anthrax typically presents with a prodromal phase (often described as flu-like) during which 

fever, chills, and cough are the most common presenting symptoms. 24, 25 Among adults, the 

most common symptoms and/or findings at admission are abnormal temperature, abnormal lung 

findings, complaint of fever or chills, tachycardia, fatigue or malaise, cough or dyspnea.24 Nonheadache neurological symptoms such as dizziness, visual changes, and syncope are also 

prominent and are key symptoms that distinguish patients with inhalational anthrax in the 

prodromal phase from patients with influenza. 24, 25 Among adult patients, with the exception of 

one patient (who was a veterinarian and thought to have partial immunity to anthrax from prior 

exposure), patients not treated during the prodromal phase progress to the fulminant phase.26 

The fulminant phase of disease is characterized by a rapidly progressive critical illness with 

respiratory failure, shock, and, usually, death. Regardless of antibiotic/anti-serum therapy or 

other medical intervention such as mechanical ventilation, the overall mortality rate in fulminant 

phase is 97% (only two patients are known to have survived the fulminant phase of inhalational 

anthrax).27-34All adult patients with inhalational anthrax who had chest roentenograms had 

abnormal findings including pleural effusions (69%) or widened mediastinum (54%).24 

Pediatric inhalational anthrax reports. There have been two English-language case 

reports of pediatric inhalational anthrax (Table 8). 
19 

The first was a 1928 report of a 21⁄2 year old girl who lived on a farm in Iowa on which 

several horses had died. She presented with a fever to 103°F; restlessness; coughing; bulging, 

erythematous tympanic membranes; and “a marked translucent edema about the eyes” that 

extended to the waist.35 Her initial lung exam was notable for “numerous fine crepitant râles 

were superimposed over tubular breathing.”35 Her laboratory tests were significant for a 

leukocyte count of 18,000 and urinalysis that was frankly purulent. Chest roentenogram 

revealed a “diffuse pneumonic process of the right lung.35 Because copious gram-positive 

organisms grew from her pleural fluid, she was given anthrax anti-serum. On hospital day ten 

she defervesced and was much improved; however, it was noted that she could not see. On 

fundoscopic examination, she was noted to have pale retinae and almost white optic cups, no 

visible veins, and arteries “that showed only as minute threads.” 35 Her clinicians concluded that 

she had suffered septic emboli of her optic arteries.35 She was discharged and on follow up 

examination was noted to be a healthy child who “walked and talked, and gave evidence of light 

perception, but no vision.”35 

The second case was a 1975 report of a 16 year old Iranian farmer girl admitted with dyspnea 

and painless swelling in her left axilla for two days.36 On admission, she was afebrile but was 

noted to have edema of her chest wall and scattered râles of the lung bases.36 Over the first 

hospital day, her axillary swelling increased in size and the skin overlying it developed petechial 

hemorrhages.36 Her leukocyte count was 33,000 with 90% neutrophils and her chest 

roentenogram showed “marked widening of the mediastinum with smooth borders and a soft 

tissue swelling over the right chest wall. The lung fields were clear.”36 She became stuporous 

and developed severe respiratory stridor and was treated with penicillin and chloramphenicol. 

On hospital day three, despite this treatment, she became hypotensive and died.36 Autopsy 

showed massive pulmonary edema, mediastinal widening with hemorrhage of the mediastinal 

lymph nodes—one of which had eroded into the carina. B. anthracis was cultured from the 

mediastinum and lungs.36 

We also found three foreign language case reports of children aged 13 to 17 for which we 

were able to obtain only scant clinical, laboratory, or disease progression data from our prior 

Evidence Report. The child who received antiserum survived, but the two children who did not 

receive therapy died (Table 8). 

A screening algorithm based principally on adult anthrax cases designed to distinguish 

patients with inhalational anthrax from those with common viral respiratory tract infections 

found that rhinorrhea and sore throat were the two symptoms most associated with viral illnesses 

(positive likelihood ratios of 0.2 [CI, 0.1-0.4] and 0.2 [CI, 0.1-0.5] respectively).25 None of the 

included pediatric patients were reported to have either of these symptoms. In this screening 

algorithm, the symptoms most suggestive of inhalational anthrax were nonheadache neurological 

symptoms (no positive likelihood ratio calculated), dyspnea (positive likelihood ratio, 5.1 [CI, 

3.0-8.5]), nausea or vomiting (positive likelihood ratio, 5.3 [CI, 3.7-7.4]), and any abnormality 

on lung auscultation (positive likelihood ratio, 8.1 [CI, 5.3-12.5]). 25 All of the children for 

whom we have signs and symptom data were found to have dyspnea and abnormal lung exams; 

however, none had either nonheadache neurological symptoms or nausea or vomiting. This 

suggests that this screening algorithm may have less diagnostic accuracy for children than for 

adults presenting with inhalational anthrax. 

In adults, pleural fluid drainage was significantly associated with survival after the 

development of fulminant inhalational anthrax.24 One child with inhalational anthrax received 

pleural fluid drainage (and she survived). However, we have insufficient cases to determine the 
20 

extent which pleural fluid drainage (or other treatment modalities) were particularly associated 

with survival. 

Summary. In the event of an aerosolized anthrax bioterrorism attack, most of the resultant 

morbidity and mortality will be from inhalational disease. The five published case reports of 

pediatric anthrax provide insufficient evidence to classify the typical presentation or treatment 

responses of children with inhalational anthrax or to compare them to adults with inhalational 

disease. However, the little evidence that is available on pediatric inhalation anthrax does 

provide us with three interesting observations. First, we note that the adolescent who received 

treatment during the fulminant phase died. This is in keeping with the high fatality rate for 

patients with fulminant inhalational anthrax observed for adult cases. Second, the two children 

who survived were treated with antiserum—a treatment not typically included in current 

treatment guidelines or bioterrorism preparedness inventories (we describe the use of anti-serum 

in greater detail in the section on treatment response in the summary of all cases at the end of this 

chapter). Finally, there is a paucity of pediatric cases in the literature for what is a relatively 

common and historically well-recognized disease. This suggests that pediatric cases may be 

under-diagnosed (we note that the presenting symptoms for pediatric inhalational anthrax are 

very common for many childhood diseases), or that children may have decreased exposure (as 

this has traditionally been an occupational illness), or that a significant publication bias may exist 

in this literature (e.g., cases that are unusual or fatal may be more likely to be published). For 

example, we question whether the case of the two year old Iowa farm girl was published because 

of the unusual complication of septic emboli, and may not represent the typical spectrum of 

presentations of inhalational anthrax. 
21 

Table 8. Pediatric inhalational anthrax case reports

Yr. (Ref.) 

Age, Gender Country 

Anthrax Exposure Risk 

Symptoms at Presentation Initial Physical Exam 

Initial Labs 

Treatment* Complica- tions‡ D

English-Language Pediatric Cases 192835 2.5, F U.S. Unknown Cough, 

restlessness 

Febrile, abnormal lung exam, cyanosis, pharyngeal erythema & edema, abdominal distension, mottled skin, erythematous bulging tympanic membranes 

WBC 18K; purulent urine 

H PE, PFD, 

C 

N

197536 16, F Iran Unknown Dyspnea, 

axilla swelling 

Abnormal lung exam, afebrile, abnormal chest roentenogram 

 P, Ch - Y

Foreign-Language Pediatric Cases190137, 38 16, F Poland Unknown "In agony" - - None M, PE Y

192939 17, M Germany Wool Fever, chills, 

pleurisy, cough, dyspnea, hemoptysis 

Febrile, tachycardia, abnormal lung exam 

- As - N

195440, 41 13,M Russia Dust from 

infected sheep and calf 

- - - None M Y

*Treatment abbreviations: As-Anthrax anti-serum, Ch-Chloramphenicol, H-Horse anti-serum, P-Penicillin. ‡Complications: M-Meningitis, C-Cyanosis, PE-Pleural effusion(s), PFD-Pleural fluid drainage. 

The symbol ‘-‘ represents either not seen prior to death or no additional signs or symptoms noted in case report at presentation. 
22 

Gastrointestinal Anthrax 

Background. Gastrointestinal anthrax results from the ingestion of B. anthracis spores 

leading to the infection (and often ulceration) of the gastrointestinal epithelium. Whereas the 

vegetative forms of B. anthracis can be killed by pasteurization, anthrax spores are robust and 

can cause disease even after exposure to heat, cold, desiccation, and exposure to acid.42 Thus, a 

bioterrorism attack in which spores were used to contaminate food or beverages could result in 

gastrointestinal disease. Additionally, after a mail-based attack (such as during 2001), 

gastrointestinal disease could occur through manual deposition of spores into the mouth or 

contamination of nearby consumables. 

Compared to inhalational and cutaneous disease, gastrointestingal anthrax is considered quite 

rare among adults, especially in the U.S. Often there have been outbreaks of several patients 

presenting with gastrointestinal anthrax after consuming contaminated meat.43 The mortality rate 

for treated gastrointestinal anthrax is generally reported as approximately 40%.42 Historically, 

gastrointestinal anthrax has been recognized as presenting in two forms: oropharyngeal disease 

among patients in whom the site of infection is the upper gastrointestinal tract and intestinal 

disease among patients in whom the site of infection is the lower gastrointestinal tract.42

Oropharyngeal anthrax presents with high fevers, ulcerations of the posterior oropharynx, severe 

sore throat, and cervical lymphadenopathy (often with marked swelling of the neck).42 In a 

report of an outbreak of adults with oropharyngeal disease contracted from consuming 

contaminated meat, three of the 24 patients died.44 

In contrast, intestinal anthrax presents with high fevers, diarrhea, severe abdominal pain, and 

serosanginous or frankly hemorrhagic ascites.42 In a report of 155 people in Uganda who ate a 

contaminated zebu, 91% developed anthrax with gastrointestinal complaints (including nine 

children who died within 48 hours of onset of symptoms2).45 Whereas bowel ulcerations are a 

common finding among adults with gastrointestinal anthrax; nonulcerative, hemorrhagic lesions 

of the bowel are often associated with anthrax sepsis from inhalational, cutaneous, and 

oropharyngeal disease.42 Abdominal roentgenograms generally reveal nonspecific findings such 

as increased bowel gas patterns with air-fluid levels or evidence of ascites.42

Pediatric gastrointestinal anthrax reports. We found 20 English-language case reports of 

pediatric gastrointestinal anthrax—most of which were associated with a known outbreak, 

typically resulting from the consumption of contaminated meat. Seven patients survived. The 

average age of these patients was 10.5 years (four children were < 2 years old, eight children 

were >2 to 13 years old; and eight children were >13 to 18 years old). Five were girls and none 

of the cases were from the U.S. 

The pediatric cases presented with symptoms similar to those reported for adults:46, 47 The 

most common presenting symptoms were fever (60%), abdominal pain (45%), and nausea and 

vomiting (45%) without any reports of hematemesis. Four patients (20%) had diarrhea and only 

one reported a bloody stool. Three cases presented with symptoms of oropharyngeal or upper 

gastrointestinal disease (Table 9). Of the three patients who went on to have abdominal surgery, 

all had mesenteric lymphadenopathy. Nine patients (45%) developed meningoencephalitis. Of 

the 19 patients for whom we were able to determine short-term survival after anthrax, 12 died 

(63% case fatality rate). 

 

2

These nine children are not included in our analysis because individual case report data have not been published for 

them. 
23 

Thirteen of the 14 patients who received antibiotics were given a regimen that included a 

penicillin-based antibiotic, ten patients received more than one antibiotic, and no patients 

received anti-serum. The use of penicillin-based antibiotics likely reflects the year of the case 

report, the country of origin of the patient, among other factors. We found no patient or 

treatment factors that were significantly associated with survival from gastrointestinal anthrax; 

however, this analysis had limited power to detect predictors of survival given the small sample 

size. However, it is notable that whereas all five girls with gastrointestinal anthrax died, only 

seven of the 14 boys with gastrointestinal anthrax died. Additionally, cases prior to 1977 were 

less likely to die (six of the eight pre-1977 cases lived) compared to more recent cases (ten of the 

11 cases after 1977 died). 

Summary. The literature on pediatric gastrointestinal anthrax (of which only eight cases 

were less than 10 years old) provides four key results. First, whereas gastrointestinal anthrax is 

much rarer than other forms of anthrax for adults, there have been many more case reports of 

gastrointestinal disease than inhalational disease among children. Clearly, children are 

susceptible to gastrointestinal anthrax from agricultural sources—whether they would be more or 

less likely to present with primary gastrointestinal disease after a bioterrorism event likely 

depends on the type of bioterrorism attack (e.g., intentional contamination of food sources or 

surfaces could result in gastrointestinal disease). Second, like adults, children have two 

presentations of gastrointestinal anthrax: upper tract disease characterized by dysphagia and 

oropharyngeal findings and lower tract disease characterized by fever, abdominal pain, and 

nausea and vomiting. Third, among the reported cases of gastrointestinal anthrax among 

children, there is a high case-fatality rate (63%). Among those who died, many had developed 

meningoencephalitis. Finally, that case reports from before 1977 were more likely to describe 

patients who lived is not readily explainable, and might represent publication bias among the 

more recent case reports. 
24 

Table 9. English-language pediatric gastrointestinal anthrax case reports

Yr. 

(Ref.) 

Age, 

Gender Country Type of GI disease§ Initial Symptoms Initial Physical Exam Treatment* Complications‡ Died 

200248 15, M Iran LG Fever, 

abd pain, diarrhea 

Febrile but vital signs otherwise normal. Abdomen tender, no splenomegaly. 

P Sh, DIC Yes Suben

hemorStomamesenedemaadenopEsopha

1991 2, F Iran LG Fever, 

abd pain, emesis 

Febrile, tachycardic, tachypneic, hypotensive Cyanosis, abd tender, distended, no bowel sounds, no skin lesions 

A, G, Ch Yes None r

200248,49 8, M Iran LG None 

reported 

None reported None 

reported 

 Yes None r

198950 11, M India LG No info Antibiotics, 

type not 

specified 

 Not 

stated

None r

197651 17, M Bangladesh LG Fever, 

anorexia, abd pain 

Febrile, no lung findings, abd tender, no distention, no hepato/splenomegaly, slight R flank tenderness, bowels sounds slightly decreased 

P, A, Ch, S, 

T, E 

T, Sh No Not ap

196543 7, M Lebanon LG Periumbili

cal pain, fever, vomiting 

Distended abd, palpable mass in R iliac fossa ascites, hypotension 

P S No Not ap

196243 17, M Lebanon LG Fever, 

abd pain 

Tender distended abdomen, ascites 

P, S S No Not ap
25 

b Table 9. English-language pediatric gastrointestinal anthrax case reports, continued

Yr. 

(Ref.) 

Age, 

Gender Country 

Type of 

GI 

disease§

Initial 

Symptoms Initial Physical Exam Treatment* Complica- tions‡ Died 

197443 15, M Lebanon LG None reported Ascites, oculofacial congestion P S, Sh No Not ap196552 14, M Thailand LG Fever, abd 

pain, emesis, diarrhea 

On admission vital signs were stable, respiratory distress, delerium, abd tender, distended, ascites 

“antimicrobials not 

given” 

Sh, RF Yes No cer

hemormesenand heulceratadeno

193253 7, M Philippines LG Fever, abd 

pain 

None reported None reported No Not ap

198954 6, M Iran LG Fever, emesis Febrile, tachypneic, nuchal 

rigidity, kernigs sign

P, S PE, PFD, 

Sh, M 

No Not ap

198954 2, F Iran LG Febrile, tachypneic, coma, 

seizure, nuchal rigidity, + kernigs, ptosis, dilatation rt pupil 

P, S M Yes None 

199755 13, M Asia LG Emesis Febrile, dehydrated, RLQ 

tenderness, no rebound or guarding, decreased bowel sounds, no meningeal or skin signs 

Cf,A, Cm MV, Sh, 

RF, DIC, 

M 

Yes Grossl

subaraof gram hemorpolys, 

199656 11, F Europe LG Fever, abd 

pain, emesis 

Febrile, ALOC, no nuchal rigidity,no skin signs

None reported MV, RF, 

M 

Yes None 

195357 15, M Africa LG Emesis Febrile, coma, no focal neuro, 

no nuchal rigidity 

P M Yes Petech

hemorlesions findinghemorsplenic of all ti

199458 13, M Asia LG Fever, abd 

pain, emesis 

None reported A, Cx, Cm,M, 

Fl, Ac 

M Yes Menin

anthra

200359 2, M Asia LG Fever, abd 

pain, emesis 

ALOC, coma None reported M Yes None 
26 

b Table 9. English-language pediatric gastrointestinal anthrax case reports, continued

Yr. 

(Ref.) 

Age, 

Gender Country 

Type of 

GI 

disease§

Initial 

Symptoms Initial Physical Exam Treatment* Complica- tions‡ Died 

197747 3 

mos, M 

India UG Emesis No fever on admission (abx 

prior), blebs, ulceration and sloughing of gums and hard palate, ulcerations covered with “dirty looking slough” 

P No Not ap

198146 18, F Turkey UG Fever, 

dyspnea, dysphagia 

None reported P,G RF Yes Brain, 

tonsillaadenofinding

198346 16, F Turkey UG Fever, 

dysphagia 

Febrile, lethargic, orolaryngeal edema, large tonsil with pseudomembrane and rightsided neck mass 

None reported Sh Yes Brain, 

tonsillaadenohemorand liv

§Type of GI disease refers to whether the primary source of infection was the upper (UG) or lower (LG) gastrointestinal tract. *Antibiotics or anthrax anti-serum. Abbreviations: A-Ampicillin, Ac-Acylovir, Ag-Amoxicillin/Clavulanate, Am-Ambramycin, As-Anthrax anti-serum, Ax

Au-Aureomycin, Az-Azithromycin, C-Ciprofloxacin, Ce-Cefamandol, Cf-Cefuroxime, Ch-Chloramphenicol, Cl-Clindamycin, Cm-Cefotaxime, Cn-Ce

Ceftazidime, D-Doxycycline, E-Erythromycin, F-Flucloxacillin, Fl-Fluconazole, G-Gentamicin, H-Horse anti-serum, L-Levofloxacin, M-Metronidazol

Rifampin, Re-Reverin, S-Streptomycin, Sd-Sulfadiazine, Sf-Sulfanilamide, St-Sulfathiazole, T-Tetracycline, Ts-Trimethoprim/Sulfamethoxazole, U-Am

Vancomycin. 

‡Complications: M-Meningitis, C-Cyanosis, DIC-disseminated intravascular coagulation, PE-Pleural effusion(s), PFD-Pleural fluid drainage, S-surgery, Sh MV-mechanical ventilation, RF-Respiratory failureT-transfusion(s)
27 

Cutaneous Anthrax 

Background. Cutaneous anthrax has long been recognized as an occupational hazard for 

adults handling contaminated animal products who introduce B. anthracis spores into the skin 

through cuts, abrasions, or insect bites.60 It is reported to account for more than 95% of clinical 

anthrax disease.61 Historically, after an incubation period of less than three days, cutaneous 

anthrax usually begins with a small, painless, pruritic papule on an exposed area.61 Classically, 

this lesion enlarges and becomes “oval eschar surrounded by vesicles with painless and marked 

edema.”62 Subcutaneously inoculated anthrax produce toxins resulting in the marked “brawny 

edema” and tissue necrosis characteristic of this disease.63 Anthrax bacilli can usually be easily 

demonstrated on gram stain smears of fluid from these lesions.61 Among adults, untreated 

cutaneous anthrax has been associated with a 5 to 20% case fatality rate (usually from 

haematologic dissemination of disease) but is rarely fatal when treated.61 During an aerosolized 

bioterrorism event with anthrax, children touching a contaminated surface may present with 

cutaneous disease. 

Pediatric cutaneous anthrax reports. We randomly selected 50 English-language case 

reports of children with cutaneous anthrax. Of these, 13 provided insufficient information about 

individual patients to be included in this analysis, 37 reports (74% of the randomly selected 

sample of cases) provided sufficient detail that data could be abstracted (Table 10). In general, 

even the included reports of pediatric cutaneous anthrax were of very poor quality, often 

providing only a few sentences about the patient and their clinical course (and rarely even 

describing the skin lesions in detail). 

The average age of these patients was 11.8 years (range: 1.5 to 18 years)—15 were less than 

10 years old (Table 7). Only seven were girls (the gender was unreported for three cases). This 

male predominance is similar to what has been observed among adults. Generally the lesions 

described were similar to the classical description of adult skin lesions with eschars surrounded 

by edema. Sixteen children received penicillin and eight had surgical debridement of their 

lesions. Only five children died (13.5% case fatality rate) which is similar to the ranges of adult 

cases. All of these were boys, three of whom had not received antibiotics. One child developed 

meningoencephalitis before he died. 

Summary. The data from our sample of 37 cases of pediatric cutaneous anthrax are limited 

by very poor reporting of disease progression, patient characteristics, and treatment information. 

Among these included cases, the skin lesions described for children are similar to the classical 

skin lesions historically described for cutaneous anthrax. Similarly, the male predominance of 

disease and case fatality rates for children were similar to what has been described for adults 

with cutaneous anthrax. 
28 

Table 10. English-language pediatric cutaneous anthrax case reports 

Yr. 

(Ref.) 

Age, 

Gender Country Symptoms at Presentation Initial Physical Exam Treatmen

1905 64 17, F G.B. Throat swelling, skin lesion Skin pustule, vesicle with edema As 

190665 18, M G.B. Painless skin lesion Fever, mildly tachycardic, pustule and 

edema 

As, FFP 

192266 16,F U.S. Skin lesion Circumscribed papulopustule Surgical debridement 

192367 17, ? U.S. Cheek lesion Cheek lesion H 

192367 14, ? U.S. Skin lesion Skin lesion H 194668 12, M Mexico Skin lesion Skin eschar and edema Cutaneous radiation r

199969 16, M Turkey Fever, throat swelling, skin lesion with 

pruritis 

Febrile, tachycardic, tachypneic, skin lesion 

P; Flouroquinolone noSteroids, surgical deb

197170 2, F Africa Fever, swelling on left side of face Febrile, left face and mouth lesion Ch; E 

200271 6, M Turkey Fever, skin lesion Febrile, Forehead lesion P 

200271 5, M Turkey Fever, skin lesion Febrile, Forehead lesion P 199863 3, F Turkey Skin lesion forehead; 

Throat swelling 

Forehead lesion P 

199863 17, M Turkey Skin lesion on fingers Finger lesion P 

199863 17, F Turkey Skin lesions on fingers Finger lesion P 193972 17, M G.B. Fever, skin lesion Fever, pustule Sulfa; As 190673 17, M G.B. Neck lesion Neck lesion General antiserum, su

debridement 
29 

Table 10. English-language pediatric cutaneous anthrax case reports, continued 

Yr. 

(Ref.) 

Age, 

Gender Country Symptoms at Presentation Initial Physical Exam 

190673 17, M G.B. Right cheek lesion Right cheek lesion Gene

surg

190673 16, M G.B. 2 pustules on arm and foot 2 pustules on arm and foot Gene

surg

 198674 3, M Africa Ectropion, no corneal scar Ectropion, no corneal scarring Left 

surge

198375 2, M Africa No sx reported Edema and eschar P 

 195876 15, M G.B. Skin lesion Nothing documented P an

amin

 193477 15, M Africa Fever, skin lesion Fever, tachycardic, tachypneic, pustule and edema Othe

 198778 9, M Turkey Fever and skin lesion Pustule and edema P, st

 193279 17, M India Fever, malaise, painful pruritic skin 

lesion 

Fever on admission, tender pustule initially, on admission evolved into vesicle 

Neosintrav

 196162 7, M U.S. No complaints Fever, rd on admission, circular black lesion on 

neck with vesicles 

P, am

 190180 16, M Italy Pustule on chin with swelling Pustule and edema As  200081 7, M Turkey Pruritic skin lesion Erythematous pustule of eyelid, with edema P 

 199682 4, M Turkey Periorbital swelling, eyelid lesion, 

visual acuity ok 

Edema and eschar, eye and vision not affected P 

 195883 17, M Mexico Right hand and forearm lesion Skin lesion on hand Amin

 194484 5, M Canada Fever, right chin blister with edema 

and induration 

Fever, tachycardia, nontender R submental blister surrounded by induration and pitting edema 

P, su

199960 18, F India None reported Edema and eschar P 
30 

Table 10. English-language pediatric cutaneous anthrax case reports, continued 

Yr. 

(Ref.) 

Age, 

Gender Country Symptoms at Presentation Initial Physical Exam 

192085 15, M US Fever on admission , initial 

headache, odynophasia and throat swelling (no skin findings reported) 

Febrile, tachycardic, tachypneic, coma and pharynx read and edematous 

 

195086 10, M India No reports Barely febrile, mild tachycardia and tachypnea. 

Vessicle, edema on back of knee, inguinal lymphadenopathy 

Ch 

200187 5, M India Febrile, no respiratory distress, 

abdominal pain, swelling of rt cheek, painless lip ulcer 

Febrile, nontoxic, extensive gelatinous edema of right cheek, nontender eschar, superficial lip lesion, no mouth involvement and cervical adenopathy 

P 

197488 2, F Africa No sx reported Vessical and edema on admission P, C

193389 <5, ? Australia Fever, skin lesions Afebrile with eschar, surrounding edema and blebs. 

No lymphadenopathy. 

Carb

190090 16, M China On admission “patient looked and felt 

very ill” with indurated mass on upper lip and black scab 

Febrile, ill-appearing with indurated mass and edema on upper lip with central eschar on admission. 

Perccarbosurg

191191 17, M U.S. Fever, lip and cheek lesion Febrile and tachycardic. Mouth, lip pustules with 

surrounding edema 

Antisseru

* Treatment with antibiotics or anthrax anti-serum. Abbreviations: A-Ampicillin, Ac-Acylovir, Ag-Amoxicillin/Clavulanate, Am-Ambramycin, As-Anthrax 

Au-Aureomycin, Az-Azithromycin, C-Ciprofloxacin, Ce-Cefamandol, Cf-Cefuroxime, Ch-Chloramphenicol, Cl-Clindamycin, Cm-Cefotaxime, Cn-Ceftria

Ceftazidime, D-Doxycycline, E-Erythromycin, F-Flucloxacillin, Fl-Fluconazole, G-Gentamicin, H-Horse anti-serum, L-Levofloxacin, M-Metronidazole, N

Rifampin, Re-Reverin, S-Streptomycin, Sd-Sulfadiazine, Sf-Sulfanilamide, St-Sulfathiazole, T-Tetracycline, Ts-Trimethoprim/Sulfamethoxazole, U-Ampi

Vancomycin.

 **This patient developed meningitis. 
31 

Atypical Anthrax 

Background. Historically, anthrax has been classified according to the three principal 

exposures: inhalational, gastrointestinal, and cutaneous. Historical reports92 and more recent 

animal data93, 94 suggest that two distinct inhalational anthrax syndromes may occur—one 

characterized by the typical and well-documented lower respiratory tract port of entry and 

another that develops after upper respiratory tract port of entry. Furthermore, some authors have 

speculated that the port of entry for primary anthrax meningoencephalitis is either an 

unrecognized lower respiratory tract port of entry 95 or transethmoid.96-98 If the variety of 

inhalational anthrax presentations is not well recognized, misdiagnosis or delayed diagnosis and 

treatment may result, thereby increasing anthrax-associated morbidity and mortality. 

In our prior Evidence Report, we found that although rare, atypical anthrax presentations do 

occur among adults.99 Specifically, we found two case reports of adults presenting with 

laryngopharyngeal anthrax, five cases of adults with nasopharyngeal anthrax, and 26 cases of 

adults presenting with anthrax meningoencephalitis without inhalational, gastrointestinal, or 

cutaneous lesions.99 (If patients presented with these atypical symptoms but were known to have 

exposure to contaminated meat, we classified them as having gastrointestinal disease.) 

Not surprisingly, patients with atypical anthrax were less likely to have a cough, chest pain, 

or abnormal lung exam than patients with typical inhalational disease.99 Adults with primary 

nasopharyngeal involvement experienced more rhinorrhea, nasal congestion or epistaxis than 

patients with typical inhalational disease.99 Patients with primary meningoencephalitis were 

more likely to experience non-headache neurologic complaints than patients with typical 

inhalational anthrax.99 The mortality rate for patients with primary anthrax meningoencephalitis 

was 97%.99

Pediatric laryngopharyngeal case results. We found 2 cases of pediatric 

laryngopharyngeal anthrax (Table 11). Both were from the same 1944 case series of East 

African presentations of atypical anthrax. Both were boys, aged 6 and 11 years, who survived. 

The 6 year old required a tracheostomy, but neither experienced disseminated intravascular 

coagulation, meningitis, respiratory failure, or septic shock. Other than noting signs of 

respiratory distress and laryngeal obstruction on admission, no other signs, symptoms, treatments 

or other clinical data are available for these boys. 

The two reports of adults with laryngopharyngeal anthrax are reviewed in detail elsewhere. 99 

Briefly, one patient was a 20 year old African man (1970) while the other was a 41 year old 

German man (1904). Both of these adults with laryngeal disease presented with neck swelling 

and ultimately died of their disease. The German patient had autopsy evidence of 

leptomengingitis, laryngeal and pharyngeal edema with epithelial necrosis but no skin, tracheal, 

bronchial, lung, or small bowel abnormalities. Given the paucity of available clinical and 

treatment details in the case reports of these four patients, we are unable to conclude whether 

adults and children with laryngopharyngeal anthrax are likely to either present or progress 

differently. 

Pediatric nasopharyngeal case results. We found one pediatric case report from 1942 of a 

17 year old Argentinean girl suspected of inhaling horsehair in a bristle mill. She went on to 

develop nasopharyngeal disease (Table 13). This patient initially presented with epistaxis, nasal 
32 

obstruction, and neck swelling, and she survived. Detailed treatment information is not available 

from this case report. Among the five adults presenting between 1902 and 1942 with 

nasal/nasopharyngeal anthrax, three worked directly with animal hair or skins, most were 

thought to have either inhaled or deposited spores directly into their noses, and most presented 

with nasal obstruction and facial swelling. Three of the six adults died. We have no treatment 

data available for any of these adult cases. Again, based on the single case report of a girl with 

nasopharyngeal disease, we cannot evaluate the salient differences between pediatric and adult 

presentations of this type of anthrax. 

Pediatric primary mengingoencephalitis case results. Of the 6 pediatric case reports of 

primary meningoencephalitis only 1 was an English-language report for which complete data are 

available.100 This patient was a 14 year old Mexican boy who was thought to have been exposed 

in a slaughterhouse. He presented with high fever but otherwise normal vital signs, headache, 

delirium, seizures, and emesis. Initial physical exam was notable for the absence of pulmonary 

symptoms. Neurological findings included meningeal signs, eye deviation with horizontal 

nystagmus and nonreactive pupils, and coma. His initial significant laboratory results included 

an elevated white blood cell count with predominance of neutrophils and a lumbar puncture with 

a markedly elevated opening pressure and elevated cerebrospinal fluid protein. He had a normal 

chest roentenogram. The patient received penicillin and chloramphenicol but succumbed 

nevertheless. At autopsy, he was found to have hemorrhagic meningoencephalitis, lung and 

splenic edema, and small bowel ulcerations. 

Among the five children described in the foreign language reports of patients with primary 

meningoencephalitis we have little patient or treatment information; however, fever, headache, 

and abdominal complaints including emesis and diarrhea were common presenting complaints. 

All five died. 

Summary: Although rare, children (particularly adolescents) do present with atypical 

presentations of anthrax. Although we cannot determine with certainty the means by which these 

patients contracted anthrax, we suspect an inhalational exposure for many, if not most, of them. 

However, some of the atypical cases may be due to unrecognized cutaneous or gastrointestinal 

exposures. We attempted to limit this situation by excluding patients with skin lesions, histories 

of consuming contaminated meat, or symptoms or autopsy findings highly suggestive of 

gastrointestinal anthrax. Additionally, the consumption of contaminated meat is unlikely to cause 

nasal or nasopharyngeal involvement. To prevent delays in diagnosis and therapy during future 

bioterrorist attacks, clinicians should recognize that anthrax infection in both adults and children 

might present with atypical presentations. 
33 

Table 11. Pediatric laryngopharyngeal anthrax case reports 

Yr. (Ref.) 

Age, Gender Country Symptoms at Presentation Initial Physical Exam Treament Complications Died Autopsy 

1944 101 6, M East Africa Dyspnea Afebrile, laryngeal obstruction Tracheostomy None reported No N/A 1944 101 11, M East Africa Dyspnea Febrile, laryngeal obstruction N/S None reported No N/A 

Table 12. Pediatric nasopharyngeal anthrax case report (non-English) 

Yr. 

(Ref.) 

Age, 

Gender Country Symptoms at Presentation Initial Physical Exam Died Autopsy Findings Suspected 

entry

1942 

102, 103

17, F Argentina Epistaxis, 

odynophagia, nasal obstruction, coryza, 

neck swelling 

Tachycardia, febrile, pharyngitis; Face, 

palate & neck edema; Nasal 

serosanguinous discharge; Cervical 

adenopathy; No skin or tonsil lesions 

No N/A Inhaled 

Table 13. Pediatric primary meningoencephalitis anthrax case report 

Yr. 

(Ref.) 

Age, 

Gender Country Anthrax Exposure Risk Symptoms at Presentation Initial Physical Exam Died Autopsy Find

English language case 

1975 

100 14, M Mexico Slaughter-house Headache, emesis, delirium, malaise, fever, seizures Febrile, comatose, neurologic deficits, meningeal signs; No 

skin or abdominal abnormalities; Normal chest roentenogram 

Yes Congested lungs§§, p

bronchopneumonia, scongestion, cerebral, hemorrhagic meningoencephalitis, ulcerations; No skin le

Foreign language cases

1981 

104

16, M Iran Unknown, 

food product 

salesman§

Headache, emesis, fever, convulsions 

Febrile, comatose, neurologic deficits, meningeal signs; No skin, lung or abdominal abnormalities 

Yes N/P 
34 

Table 13. Pediatric primary meningoencephalitis anthrax case report, continued 

Yr. 

(Ref.) 

Age, 

Gender Country Anthrax Exposure Risk Symptoms at Presentation Initial Physical Exam Died Autopsy 

Foreign language cases, continued 

1951 

105 1, F Italy N/S Fever, diarrhea, restlessness Febrile; Tonsillar & oral cavity erythema/edema without 

ulceration/plaques; No skin, lung or abdominal abnormalities 

Yes N

1940 

106 17, M Germany N/S Fever, headache, back pain, stomach complaints Febrile; No skin, lung or abdominal abnormalities; No 

neurologic deficits 

Yes N

1936 

107

18, M Romania N/S Fever, headache, abdominal 

pain, delirium 

Comatose, cyanosis, abnormal lung exam, abdominal distension, neurologic deficits; No skin lesions 

Yes Hemorrhagic 

meningoencephand mesenteric without bowel ulung or skin lesi

1927 

108

11, M France Horses, cattle Anorexia, headache, chills, 

malaise, fatigue, emesis, delirium 

Febrile, tachycardia, neurologic deficits, menigeal signs; No skin, throat, lung or abdominal abnormalities 

Yes N

* We classified cases according to one of three anatomical sites: nasal/nasopharyngeal, larygeal/laryngopharyngeal, or primary meningoencephalitis (wit

gastrointestinal, or respiratory port of entry). Cases were classified primary according to the primary author(s) suspicion for the port of entry as well th

mucosol and lymph node abnormalities on exam or at autopsy. 

Table Abbreviations: Ref=Reference(s); Yr=Year; F=Female; M=Male; U.S.=United States; G.B.=Great Britain; N/A=Not applicable; N/S=Not specifie

GI=Gastrointestinal; CT=Computed tomography 

‡‡ What the primary author(s) of the case report suspected as the route of entry for Bacillus anthracis spores. §§ The primary author suspected a primary nasopharyngeal infection with a secondary stomach/intestinal infection from swallowing nasal secretions. ¶¶ Throat swabs cultured Bacillus anthracis with no other pathogenic organisms. 
35 

Summary Analyses Including All Cases 

The included cases were highly heterogeneous in terms of their clinical presentations and 

treatments received. 

Clinical Presentations 

 Among the 59 case reports which stated the patient’s gender, only 14 (24%) were girls. 

This is similar to the gender discrepancy observed among adults and has historically been 

attributed to the fact that anthrax has largely been an occupational disease among professions 

(e.g., woolsorters and butchers) traditionally dominated by men. However, other biases may be 

contributing to the under-diagnosis and under-reporting of anthrax in girls relative to boys. 

 Eleven patients were reported to have had chest roentgenograms. Both of the patients with 

inhalational anthrax were found to have abnormalities on chest roentenogram. Of the four 

patients with gastrointestinal anthrax who had roentgenograms, two were found to have 

pulmonary abnormalities, one patient had “ascites but no other abnormalities,” and one had a 

normal examination. All four of the patients with cutaneous anthrax had normal chest 

roentgenograms. We conclude that the role of roentgenograms for diagnostic decision making in 

pediatric anthrax is not well established. 

Among the included cases, nine developed meningoencephalitis (seven of these had 

gastrointestinal anthrax, one had cutaneous anthrax, and one had primary anthrax 

meningoencephalitis). All but one of these patients died. 

Treatment Responses 

 Prior to the introduction of antibiotics, anthrax infection was primarily treated with antiserum.109 Anthrax anti-serum reportedly decreased mortality by 75% compared to untreated 

patients.110-115 and its efficacy is supported by recent animal data.116 However, anaphylactic 

reactions and serum sickness were major side-effects. 117 Because anthrax virulence is caused by 

the production of two bacterial toxins, lethal factor and edema factor,10 it has been theorized that 

therapeutics (such as antiserum) directed against these toxins could be superior to antimicrobial 

agents.117-122 Additionally, the efficacy of anthrax immune therapy is supported by recent animal 

data using neutralizing monoclonial antibodies.116, 123-125 In the 1940’s effective antibiotics such 

as penicillin and chloramphenicol were added to anthrax treatment strategies.86, 126 Anthrax antiserum is no longer commercially available in most western countries including the U.S., but is 

still available in the Russian Federation and in China.117, 127, 128 Recently, the U.S. Department of 

Health and Human Services awarded a contract to the Cangene Corporation (Winnipeg, Canada), 

to produce anthrax immune globulin between 10,000 and 100,000 doses for the Strategic 

National Stockpile.129-134 Anthrax immune globulin is a highly purified human antibody that is 

specific to anthrax and is collected from the plasma of soldiers who were inoculated with the 

anthrax vaccine.123, 135 Additionally, Human Genome Sciences, Inc. (Rockville, Maryland) was 

awarded a similar contract to develop a monoclonal antibody inhibitor specific for anthrax 

protective antigen to also be included within the Strategic National Stockpile.12, 131-134, 136, 137
36 

The included cases differed with respect to their treatments and treatment responses (Table 

14). Overall, the mortality rate was 31% (19 of 61; note, survival information was not available 

for one patient). There was no significant association between gender or age and survival. 

Among those patients who received antibiotics, 71% survived compared to 82% survival among 

those patients who received antiserum. Only one patient was treated with a fluroquinolone. 

Current treatment guidelines for inhalational or gastrointestinal anthrax in children vary among 

different professional organizations; however, most recommend triple intravenous antibiotics 

with ciprofloxacin or doxycycline with two other antibiotics such as clindamycin, rifampin, 

penicillin, among others.9, 12, 138-141 Recommended treatment for cutaneous anthrax is with one 

oral antibiotic: penicillin, amoxicillin, ciprofloxacin, or doxycycline.9, 12, 138-141 

None of the included patients received anthrax vaccine. The currently licensed, Anthrax 

Vaccine Adsorbed (AVA, Bioport Corporation, Lansing, MI) may have a role in post-exposure 

prophylaxis;142 however, it is currently only approved for 18 to 65 year olds.1, 12

We had initially hoped to be able to evaluate the effect of time to onset of treatment on 

disease progression; however, insufficient evidence was available from the case reports to 

perform this analysis. 

Table 14. Summary of treatments received 

Treatment Received Number of 

Patients 

Number who Lived 

(%) 

P value*

Any antibiotic vs. no antibiotic or antiserum 38 27 (71%) 0.78 

Penicillin or penicillin-based antibiotic (e.g., 

ampicillin) vs. all other treatments 

30 19 (63%) 0.89 

Antiserum vs. all other treatments 11 9 (82%) 0.29 

Aminoglycosides (most often streptomycin) vs. 

all other treatments 

10 7 (70%) 0.85 

Chloramphenicol vs. all other treatments 8 5 (63%) 0.91 

Fluoroquinolones vs. all other treatments 1 1 (100%) 0.44 *

P value for the comparison of whether patients who received this treatment were more likely to survive than those who did not 

receive this treatment. 

Summary Answers to the Key Questions 

Key Question #1: What Is the Evidence for an Age-dependent Disease 

Progression Associated With Anthrax? 

Although children with anthrax may present with somewhat different symptoms than adults, 

we found no specific evidence for age-dependent differences in disease progression. Like adults, 

children with gastrointestinal anthrax, seem to have two distinct clinical presentations: One 

resulting from upper tract disease and another resulting from lower tract disease. Additionally, 

children with inhalational disease may have non-pulmonary presentations including primary 

meningoencephalitis. 
37 

Key Question #2: How Effective Are Antibiotic Prophylaxis and 

Treatment for Anthrax in Children Compared to Adults? Similarly, 

How Effective Are Other Medical Treatments in Children Compared to 

Adults (e.g. Ventilator/Respiratory Support)? 

Most of the children included in our analysis who received an antibiotic were given 

penicillin-based antibiotics which produced a 63% survival rate. Other successful treatments 

included antiserum, which produced an 82% survival rate. These survival rates were similar to 

those observed for adults. 

In adults, pleural fluid drainage was significantly associated with survival after the 

development of fulminant inhalational anthrax.24, 143 One child with inhalational anthrax 

received pleural fluid drainage and she survived. However, we found insufficient cases of 

children who received pleural fluid drainage (or other treatment modalities such at mechanical 

ventilation) to determine the extent which they may be more or less effective in children than 

they are in adults.

Key Question #3: Based on the Review of Evidence for Questions 1 

and 2, What Are the Implications for Children Versus Adults in Terms 

of Preparedness and Response Planning for Anthrax exposure (i.e., 

Healthcare Provider Education on Diagnosis and Management, 

Considerations for Hospitals, Vaccination Strategies)? 

The results of our systematic review have implications for preparedness planning efforts that 

relate to the diagnosis and management of children with anthrax. The presenting signs and 

symptoms of children with anthrax are very similar to the signs and symptoms of children 

presenting with much more common infectious diseases. This creates a difficult diagnostic 

challenge both for clinicians needing to make a timely diagnosis and public health officials 

implementing syndromic surveillance systems. More research is needed to identify the specific 

signs and symptoms (e.g., rhinorrhea) that distinguish common pediatric infections such as 

influenza from early anthrax infection.144 

Only one of the 62 pediatric anthrax cases was treated with a fluoroquinolone; however, 

penicillin-based and antiserum regimens were much more commonly used among the included 

cases and were associated with favorable survival rates. Antiserum is not included in current 

treatment guidelines or bioterrorism preparedness inventories and has been associated with 

serum sickness and inconsistency in effectiveness across batches. Similarly, current treatment 

guidelines do not include penicillin as a single agent due to concerns of penicillin-resistant 

organisms.9, 138-141 Thus, we have little evidence about the use of the medical regimens currently 

considered first line against anthrax and more evidence about those therapies not currently being 

recommended. 

39 

Chapter 4. Discussion 

This is the first published synthesis of the literature describing the spectrum of clinical 

anthrax in children. The 62 English-language pediatric cases included in this review provide 

four key findings. 

First, children with anthrax present with a wide range of clinical signs and symptoms—which 

differ somewhat from the presenting features of adults with anthrax. Like adults, children with 

gastrointestinal anthrax have two distinct clinical presentations: One resulting from upper tract 

disease characterized by dysphagia and oropharyngeal findings and another resulting from lower 

tract disease characterized by fever, abdominal pain, and nausea and vomiting. Additionally, 

children with inhalational disease may have atypical presentations including primary 

meningoencephalitis. Clinicians and public health officials need to recognize the broad spectrum 

of potential presentations of anthrax in children for timely diagnosis and for the design of 

syndromic surveillance systems.144 

Second, whereas children with inhalational anthrax did have abnormal chest roentgenograms, 

children with other forms of anthrax often had normal roentgenograms. Thus, the usefulness of 

roentgenograms in the early diagnosis of non-inhalational anthrax disease may be limited. 

Third, most of the children included in our analysis who received an antibiotic were given 

penicillin-based antibiotics which produced a 63% survival rate. Other successful treatments 

included antiserum, which produced a 82% survival rate. Antiserum is not typically included in 

current treatment guidelines or bioterrorism preparedness inventories. Similarly, current 

treatment guidelines do not include penicillin as a single agent due to concerns of penicillinresistant organisms.9, 138-141 Only one child received a fluoroquinolone—which is a key 

component of current treatment guidelines for children with anthrax. In the event of shortfalls in 

stockpiles of the currently recommended antibiotics, penicillin or antiserum may provide some 

therapeutic benefit. 

Finally, anthrax is a relatively common and historically well-recognized disease and yet 

rarely reported among children. We did not find evidence to support or refute the claim that 

children may be less susceptible to anthrax infection. In general, the relatively small number of 

pediatric cases of anthrax may reflect that this has traditionally been an occupational disease so 

that, particularly young children, may not have the same degree of exposure to anthrax spores. 

Additionally, the paucity of pediatric anthrax case reports suggests that anthrax may be underdiagnosed in children. Under-diagnosis and under-reporting of anthrax is likely to occur for 

several reasons: The presenting symptoms for pediatric inhalational anthrax are very common 

for many childhood diseases and since acute respiratory infections are the second leading cause 

of death worldwide for children under five years old, it is highly likely that naturally occurring 

pediatric anthrax has been attributed to one of the common childhood respiratory infections.145, 

146 Additionally, naturally occurring anthrax disease is most prevalent in poor countries with few 

healthcare resources and high infant mortality rates, where children may never come to medical 

attention or have diagnostic cultures confirmed.147 Also, clinicians may be unlikely to report a 

case without culture confirmation which can be difficult since B. anthracis is quickly cleared 

after the initiation of antibiotics. 
40 

Limitations 

 This review has several limitations. First, because we did not have access to the original 

hospital and medical records, our analyses are dependent upon the data presented in the case 

reports. Second, because most of the patients in our review are presumed to have contracted 

anthrax from an occupational exposures or direct contact with contaminated animal products, our 

results may have limited generalizability to anthrax infection that occurs from bioterrorism. 

However, we cannot assess the extent to which differences in virulence and inoculating doses 

between anthrax infection from bioterrorism and from occupational exposure may result in 

differences in clinical presentations and treatment responses. Third, among the included cases, 

most were of older children. Thus, our results may not be generalizable to infants and toddlers 

with anthrax. Finally, the general paucity of pediatric cases suggests that there may be a 

significant publication bias in this literature. 

Future Research 

In order to facilitate accurate diagnosis and effective treatment of children with anthrax, 

future pediatric anthrax case reports should provide much more detailed information about 

exposure, clinical presentation, and treatment responses (such as those data described in 

Appendix A). 

The finding that children may not present with the same signs and symptoms as adults has 

implications for syndromic surveillance systems. An evaluation of a drop-in syndromic 

surveillance system compared the syndromic categorization by emergency department staff in 11 

Phoenix hospitals with chief complaints and discharge diagnoses.148 Overall, agreement between 

the syndromic categorization and the discharge diagnoses was moderate (κ =0.63; [CI, 0.59-

0.67]) with the greatest agreement for the gastroenteritis/diarrheal syndrome and lowest for the 

febrile respiratory tract infection syndrome.148 However, pediatric chief complaints showed 

lower agreement for the febrile respiratory tract infection syndrome when compared with adults 

(κ = 0.34 [95% CI = 0.20 to 0.47] versus κ = 0.44 [95% CI = 0.28 to 0.59], respectively). 148 

This suggests that additional research is needed on the presenting signs and symptoms of 

pediatric anthrax to inform the development of pediatric syndromic surveillance categories. 

Additionally, to determine the extent to which children and adults differ with respect to the 

prevention and treatment of anthrax-associated morbidity and mortality, comprehensive 

evaluations are required of the safety and efficacy of prophylactic vaccines, the role of various 

antibiotics (including those not currently recommended in prophylaxis and treatment guidelines), 

and the role of non-antibiotic therapies such as antiserum and pleural fluid drainage. 

 
41 

Conclusions 

The limited data available on children with anthrax suggest that their clinical presentation 

and treatment responses differ somewhat from adults with anthrax. Clinicians and public health 

officials should be aware of these differences for the timely diagnosis of children with anthrax 

and for the development of syndromic surveillance tools for populations that include pediatric 

patients. 

43 

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49 

U.S. Department of Health and Human Services 

Mike Leavitt, Secretary 

Office of Public Health and Science 

Richard H. Carmona, M.D., M.P.H., F.A.C.S., Surgeon General of the United States

Agency for Healthcare Research and Quality 

Carolyn M. Clancy, M.D., Director 
A-1 

Appendix A. Data Abstracted 

Reference ID 

Age 

Year 

Gender 

Country 

Type 

Source 

Language 

Pregnant woman or prenatal case 

Case part of a known anthrax outbreak 

Patient Identification

Confirmed case 

Penicillin 

Other penicillinoid antibiotics (e.g., amoxicillin) 

Chloramphenicol 

Fluoroquinolone 

Cephalosporin 

Aminoglycoside 

Sulfa-based antibiotics 

Tetracycline antibiotic 

Macrolide antibiotic (e.g. Erythromycin) 

Carbapenem (e.g. Imipenem) 

Antibiotics 

Other antibiotic 

Anti-anthrax serum (i.e., Sclavo's serum) Serum 

General serum 

(e.g., bovine or horse serum) 

Antibiotics 

Serum 

Steroids 

Intrathecal 

Other 

Steroids 

Radiation therapy 

Surgical debridement 

Other 

Pressor support 

Thoracentesis Pleural 

Chest tube placement 

Intubation 

Airway Tracheostomy 

Mechanical ventilation 

Red blood cells 

Plasma 

Platelets 

Treatments 

(Abstracters noted whether patients 

received any of these treatments 

and, if so, whether they received 

them in the early phase of illness or 

late in the patient’s course of 

disease.) 

 

Transfusions 

Other 

Meningitis 

Shock 

Respiratory Failure 

Disseminated intravascular coagulation 

Laryngeal edema/Compromise of the airway from swelling 

Clinical Outcome(s) 

(Abstracters noted whether any of 

these occurred at any time during 

the patient’s anthrax-related illness.)

 Died
Appendix A. Data Abstracted, Continued 

A-2 

White Blood Cell Count 

%Neutrophils 

%Lymphocytes 

%Monocytes 

%Eosinophils 

Hemoglobin 

Hematocrit 

Platelets 

Erythrocyte Sedimentation Rate 

Hematology 

C-Reactive Protein 

Sodium 

Potassium 

Bicarbonate 

Creatinine 

BUN 

Glucose 

Chemistries 

Calcium 

Albumin 

 Protein 

AST 

ALT 

Liver Function Tests 

Total bilirubin 

INR 

Prothrombin Time 

Partial Thromboplastin Time 

D-dimer 

Serum/Blood Laboratory Studies 

(Abstracters noted the results of 

these tests on admission, and again 

if they were done later in the course 

of the patient’s anthrax-related 

illness.) 

Coagulation Tests 

Fibrinogen 

Opening Pressure 

White Blood Cell Count 

% Neutrophils 

% Lymphocytes 

% Monocytes 

Red Blood Cell Count 

Glucose 

Total Protein 

Lumbar puncture/Cerebrospinal 

fluid analysis

Gross Appearance 

White Blood Cell Count

%Neutrophils

%Lymphocytes

%Monocytes

Red Blood Cell Count

Glucose

Total Protein

Thoracentesis/Pleural fluid 

analysis

Gross Appearance
Appendix A: Data Abstracted, Continued 

 A-3 

Widened mediastimum 

Pleural effusion 

Focal airspace opacity or infiltrates 

Hilar masses or opacities 

Chest Roentengram 

Other findings 

Head/Brain Computed Tomography Findings 

Chest Computed Tomography Findings 

Radiological Studies

Abdominal or pelvic Computed 

Tomography Findings 

Gram Stain Findings Blood 

Culture Findings 

Gram Stain Findings CSF

Culture Findings 

Gram Stain Findings Pleural Fluid 

Culture Findings 

Gram Stain Findings Skin/Cutaneous Lesion

Culture Findings 

Gram Stain Findings Sputum Culture Findings 

Gram Stain Findings 

Microbiology from samples taken 

while patient was alive 

(Abstracters noted whether these 

results were obtained before or after 

the administration of antibiotics or 

anti-sera.) 

Other (Specify) Culture Findings 

Gram Stain Findings Blood 

Culture Findings 

Gram Stain Findings CSF

Culture Findings 

Gram Stain Findings Pleural Fluid

Culture Findings 

Gram Stain Findings Brain Tissue

Culture Findings 

Gram Stain Findings Lung/Pleura Culture Findings 

Gram Stain Findings Mediastinum

Culture Findings 

Gram Stain Findings Stomach 

Culture Findings 

Gram Stain Findings Small Intestines

Culture Findings 

Gram Stain Findings Mesentery Culture Findings 

Gram Stain Findings 

Autopsy Microbiology

Other (Specify) Culture Findings 
Appendix A: Data Abstracted, Continued 

A-4 

Evidence of Encephalitis Brain 

Hemorrhage 

Evidence of Meningitis Meninges Hemorrhage 

Nasal or nasopharyngeal lesion/edema 

Oral lesion or edema 

Tonsilar lesion/edema 

Laryngeal lesion/edema 

Sinus lesion or hemorrhage 

Head or neck adenopathy 

Head 

Face or neck edema 

Edema or congestion 

Lungs Hemorrhage 

Infiltrates 

Effusion Pleura 

Hemorrhagic 

Edema 

Mediastinum Hemorrhage 

Adenopathy 

Edema 

Stomach Hemorrhage 

Ulceration 

Edema 

Small Bowel Hemorrhage 

Ulceration 

Ascites 

Edema 

Hemorrhage Mesentery 

Adenopathy 

Edema Spleen Hemorrhage 

Skin Lesions 

Autopsy Findings 

Other relevant findings 

Fever 

Chills or rigors 

Diaphoresis or night sweats 

 Malaise 

Fatigue, weakness or exhaustion 

Myalgias, muscle pain, non-joint extremity pain 

Arthralgia 

Anorexia 

Back pain 

If report stated that the patient had "Common cold symptoms" 

If report stated that the patient had "flu-like symptoms" 

Ear pain 

Red eye 

Irritability 

Decreased PO Intake 

Decreased urine output 

Symptoms General Complaints 

Infants with grunting, flaring, or retractions 
Appendix A: Data Abstracted, Continued 

A-5 

Cough 

Productive sputum 

Hemoptysis 

Shortness of breath or dyspnea 

Chest pain 

Pleurisy or pleuritic chest pain 

Wheezing 

Respiratory Complaints 

Respiratory distress 

Nasal congestion or stuffiness 

Coryza: A "cold in the head" caused by inflammation of the mucous 

membrane lining the nose (usually associated with nasal discharge) 

Rhinitis - an inflammation of the mucous membrane lining the nose (usually 

associated with nasal discharge). 

Rhinorrhea: Nasal discharge (i.e. runny nose) of any mucus-like material that 

comes out of the nose. 

Nasal pain 

Nasal/Sinus Complaints 

Sinus complaints 

Abdominal pain, irritation or indigestion 

Nausea 

Emesis 

Hematemsis 

Diarrhea 

Gastrointestinal 

Complaints 

Hemtochezia or tarry stools 

Headache 

Dizziness, giddiness or vertigo 

Syncope 

Agitation or restlessness 

Insomnia 

Focal neurologic (motor or sensory) complaints 

Altered mental status, delirium, confusion 

Neurological Complaints 

Visual complaints 

Odynophagia (mouth pain) or pharyngitis (sore throat) 

Dysphagia or difficulty swallowing 

Laryngeal obstruction or choking 

Trismus: Inability to open the mouth fully 

Neck or Throat 

Complaints 

Neck swelling 

Any skin lesion (note location(s)) 

Skin lesions If skin lesions are present, are they painful 

Pruritus 

Symptoms 

Continued

Other relevant symptoms

Temperature (or note if article states “febrile”, etc.) 

Heart rate (or note if article states “tachycardia”, etc.) 

Systolic blood pressure (or note if article states “hypotensive”, etc.) 

Respiratory rate (or note if article states “tachypnea”, etc.) 

Vital signs 

Either O2Sat or PaO2 (state if on room air or if on oxygen) 

Cyanosis 

Respiratory distress 

Cold or clammy skin 

Diaphoretic 

Clinical Findings 

General findings 

Infants with grunting, flaring nostrils or retractions 
Appendix A. Data Abstracted, Continued 

A-6 

Rales or rhonchi 

Wheezing 

Dullness to percussion 

Decreased breath sounds 

Bronchial or tubular breath sounds 

Lung Exam 

Any other pulmonary abnormality 

Abdominal tenderness 

Abdominal distension 

Spenomegaly 

Enlarged liver 

Ascites 

Abdominal exam 

Any other abdominal abnormality 

Orthostatic dizzy 

Altered mental status or lethargy 

AMS 

Coma or stupor 

Focal neurologic (motor or sensory) deficits 

Hypperreflexia 

Cranial nerve deficits 

Seizure 

Opithotonus: arching of back (also seen with meningitis) due to irritated 

meninges. 

Nuchal rigidity 

Positive Kernig or Brudzinski 

Photophobia 

Neurological deficits 

Other neurological abnormalities 

Congestion 

Nasal obstruction 

Internal nasal lesion or abscess 

Nasal exam 

Other nasal abnormality 

Pustule 

Vesicle 

Malignant edema (erysipelatous) 

Eschar 

If a skin lesion is present, is it tender 

Skin 

Any other skin/cutaneous abnormality 

Erythema or injection 

Edema 

Abscess 

Pharyngeal 

(oral/naso/laryngo) 

Any other pharyngeal abnormalities 

Cervical 

Lymph nodes Axillary 

Any other adenopathy 

Conjunctivitis Eye Any other eye abnormalities 

Otitis/tympanic membrane abnormalities 

Clinical Findings 

Continued

Ear 

Any other ear abnormalities 
B-1 

Appendix B: Adult Anthrax Case Reports Not Included in 

This Analysis 

Adult Inhalational Cases 

1. Inglesby TV, O'Toole T, Henderson DA, et al. Anthrax as a biological weapon, 

2002: updated recommendations for management. JAMA. 2002;287(17):2236-52 

2. Brachman PS. Inhalation anthrax. Ann N Y Acad Sci. 1980;353:83-93. 

3. Jernigan JA, Stephens DS, Ashford DA, et al. Bioterrorism-related inhalational 

anthrax: The first 10 cases reported in the United States. Emerg Infect Dis. 

2001;7(6):933-944. 

4. Regan JC. The advantage of serum therapy as shown by a comparison of various 

methods of treatment of anthrax. Am J Med Sci. 1921;162:406-423. 

5. Sclavo A. Sullo stato presente della sieroterapia anticarbonchiosa. Rivista di Igiene e 

Sanita pubblica. 1903;14:519-587. 

6. Henderson DW, Peacock S, Belton FC. Observations on the prophylaxis of 

experimental pulmonary anthrax in the monkey. J Hyg (London). 1956;54:28-36. 

7. Lucchesi PF. Serum treatment of 19 cases of anthrax including one of external, 

internal and bacteremic type. Am J Med Sci. 1932;183(6):795-802. 

8. D'Agostino S, Maddaluno R. Considerazioni su 593 casi di carbonclio umano. Agg 

Pediatr. 1962;13:663-676. 

9. Karginov V, Robinson T, Riemenschneider J, et al. Treatment of anthrax infection 

with combination of ciprofloxacin and antibodies to protective antigen of Bacillus 

anthracis. FEMS Immunol Med Microbiol. 2004;40(1):71-4. 

10. Heilman FR, Herrell WE. Penicillin in the treatment if experimental infections with 

Bacillus anthracis. Proc Staff Meetings Mayo Clin. 1944;19:492-496. 

11. Clarke PS. Chloramphenicol in the treatment of cutaneous anthrax. BMJ. 

1952;1(4759):86-87. 

12. CDC. Update: Investigation of bioterrorism-related anthrax and interim guidelines 

for exposure and interim guidelines for exposure management and antimicrobial 

therapy. MMWR Morbidity & Mortality Weekly Report. 2001;50(42):909-919. 

13. Schwartz M. Recognition and management of anthrax - an update. New England J 

Med. 2001;345:1621-26. 
Appendix B: Adult Anthrax Case Reports Not Included in This Analysis, Continued 

B-2 

14. Inglesby TV, O'Toole T, Henderson DA, et al. Anthrax as a biological weapon, 

2002: Updated recommendations for management. JAMA. 2002;287(17):2236-52. 

15. Brachman PS, Kaufmann A. Anthrax (Chapter 4). In: Evans AS, Brachman PS, eds. 

Bacterial Infections of Humans. Epidemiology and Control. 3rd ed. New York: 

Plenum; 1998:95-107. 

16. Brachman PS. Anthrax. Ann N Y Acad Sci. 1970;174(1):577-582. 

17. Friedlander AM. Anthrax (Chapter 22). In: Zajtchuk R, Bellamy RF, eds. Textbook 

of Military Medicine: Medical Aspects of Chemical and Biological Warfare. Vol. 5. 

Washington, D. C.: Office of the Surgeon General; Department of the Army, U. S. 

A.; 1997:467-478. 

18. Brachman PS, Plotkin SA. An epidemic of inhalation and cutaneous anthrax: 

Studies of Anthrax in a goat hair mill in New Hampshire; Final Report. Anthrax 

Investigations Unit, Epidemiology Branch, Communicable Disease Center, Public 

Health Service, U. S. Department of Health, Education and Welfare; Dec 1, 1959. 

19. Koch R. [The etiology of anthrax, based on the life history of Bacillus anthracis]. 

Beitr Biol Pflanz. 1877;2:277-308. 

20. McFadyean J. Extraneous sources of infection in outbreaks of anthrax. J Comp 

Path. 1903;16:346-357. 

21. Eurich FW, Hewlett RT. Bacillus anthracis. In: Topley WWC, ed. A System of 

Bacteriology in Relation to Medicine. Vol. 5. London: Majesty's Stationary Office; 

1930:439-478. 

22. Barakat LA, Quentzel HL, Jernigan DB, et al. Fatal inhalational anthrax in a 94 year 

old Connecticut woman. JAMA. 2002;287(7):863-868. 

23. Mina B, Dym JP, Kuepper F, et al. Fatal inhalational anthrax with unknown source 

of exposure in a 61 year old woman in New York City. JAMA. 2002;287(7):858-

862. 

24. Pile JC, Malone JD, Eitzen E, Friedlander A, M,. Anthrax as a potential biological 

warfare agent. Arch Intern Med. 1998;158(5):429-34. 

25. Cavallo JD, Ramisse F, Girardet M, Vaissaire J, Mock M, Hernandez E. Antibiotic 

susceptibilities of 96 isolates of Bacillus anthracis isolated in France between 1994 

and 2000. Antimicrob Agents Chemother. 2002;46(12):3843-5. 

26. Coker PR, Smith KL, Hugh-Jones ME. Antimicrobial susceptibilities of diverse 

Bacillus anthracis isolates. Antimicrob Agents Chemother. 2002;46(12):3843-5. 
Appendix B: Adult Anthrax Case Reports Not Included in This Analysis, Continued 

B-3 

27. Mohammed MJ, Marston CK, Popovic T, Weyant RS, Tenover FC. Antimicrobial 

susceptibility testing of Bacillus anthracis: comparison of results obtained by using 

the National Committee for Clinical Laboratory standards broth microdilution 

reference and Etest agar gradient diffusion methods. J Clin Microbiol. 

2002;40(6):1902-7. 

28. Garrod LP. The sensitivity of Bacillus anthracis to antibiotics. Antibiot Chemother. 

1952;11(12):689-692. 

29. Turnbull BW. The empirical distribution function from arbitrarily grouped, censored 

and truncated data. Journal of Royal Statistical Society, Series B. 1976;38:290-295. 

30. Bravata DM, Owens DK, McDonald KM, et al. Regionalization of Bioterrorism 

Preparedness and Response - Evidence Report/Technology Assessment, Prepared 

by the Stanford University - University of California San Francisco Evidence-based 

Practice Center under contract number 290-02-0017. Rockville, MD: Agency for 

Healthcare Research & Quality; 2004. 

31. Johnson K. A nation challenges: the victim; By demanding a diagnosis, he lives to 

tell of anthrax. New York Times 2001 December 3;1. 

32. Teacher JH. Primary intestinal anthrax in man; septicaemia; haemorrhagic leptomeningitis. Lancet. 1906;1:1306-1311. 

33. Teacher JH. Case of human anthrax septicaemia: infection through the intestine: 

Diffuse meningeal haemorrhage. Glasgow Med J. 1905;64:127-131. 

34. Teacher JH. A case of primary intestinal anthrax in man. Lancet. 1906;2:830. 

35. Haight TH. Anthrax meningitis: a review of the literature and report of two cases 

with autopsies. Am J Med Sci. 1952;224(1):57-59. 

36. Brachman PS, Plotkin SA, Bumford FH, Atchison MM. An epidemic of inhalation 

anthrax: the first in the twenieth century, II. Epidemiology. Am J Hyg. 1960;72:6-

23. 

37. Brachman PS, Gold H, Plotkin SA, Fekety FR, Werrin M, Ingraham NR. Field 

evaluation of a human anthrax vaccine. Amer J Public Health. 1962;52(4):632-45. 

38. Plotkin SA, Brachman PS, Utell M, Bumford FH, Atchison MM. An epidemic of 

inhalation anthrax. Am J Med. 1960;29:992-1001. 

39. Plotkin SA, Brachman PS, Utell M, Bumford FH, Atchison MM. An epidemic of 

inhalation anthrax, the first in the twentieth century: I. Clinical features. Am J Med. 

2002;112:4-12. 
Appendix B: Adult Anthrax Case Reports Not Included in This Analysis, Continued 

B-4 

40. Bales ME, Dannenberg AL, Brachman PS, Kaufmann A, Klatsky PC, Ashford DA. 

Epidemiologic response to anthrax outbreaks: field investigations, 1950-2001. 

Emerg Infect Dis. 2002;8(10):1163-74. 

41. Gill JR, Melinek J. Inhalational anthrax: gross autopsy findings. Arch Pathol Lab 

Med. 2002;126(8):993-4. 

42. Jernigan JA, Raghunathan PL, Bell BP, et al. Investigation of bioterrorism-related 

anthrax, United States, 2001: Epidemiologic findings. Emerg Infect Dis. 

2002;8(10):1019-28. 

43. Guarner J, Jernigan JA, Shieh WJ, et al. Pathology and pathogenesis of 

bioterrorism-realted inhalational anthrax. Am J Pathol. 2003;163(2):701-9. 

44. Bush LM, Abrams BH, Beall A, Johnson CC. Index case of inhalational anthrax due 

to bioterrorism in the United States. N Engl J Med. 2001;345(22):1607-10. 

45. Traeger MS, Wiersema ST, Rosenstein NE, et al. First case of bioterrorism-related 

inhaltional anthrax in the United States, Palm Beach County, Florida, 2001. Emerg 

Infect Dis. 2002;8(10):1029-34. 

46. Maillard JM, Fischer M, McKee KT, Jr., Turner LF, Cline JS. First case of 

bioterrorism-related inhalational anthrax, Florida, 2001: North Carolina 

investigation. Emerging Infectious Diseases. 2001;8(10):1035-8. 

47. Mayer TA, Bersoff-Matcha S, Murphy C, et al. Clinical presentation of inhalational 

anthrax following bioterrorism exposure: report of 2 surviving patients. JAMA. 

2001;286(20):2549-53. 

48. Dewan PK, Fry AM, Laserson K, et al. Inhalational anthrax outbreak among postal 

workers, Washington, D. C., 2001. Emerg Infect Dis. 2002;8(10):1066-72. 

49. Earls JP, Cerva D, Berman EL, et al. Inhalational anthrax after bioterrorism 

exposure: spectrum of imaging findings in two surviving patients. Radiology. 

2001;222(2):305-12. 

50. Borio L, Frank D, Mani V, et al. Death due to bioterrorism-related inhalational 

anthrax: report of 2 patients. JAMA. 2001;286(20):2554-59. 

51. Quintilliani Jr. R, Mahajan AK, Quintilliani R. Fatal Case of Inhalational anthrax 

mimicking intra-abdominal sepsis. J Ibaraki Health Science Center. 2001;47:3-8. 

52. Quintilliani Jr. R, Quintilliani R. Fatal case of inhalational anthrax mimicking intraabdominal sepsis. Conn Med. 2002;66(5):261-67. 
Appendix B: Adult Anthrax Case Reports Not Included in This Analysis, Continued 

B-5 

53. Wood BJ, DeFranco B, Ripple M, et al. Inhalational anthrax: Radiologic and 

pathologic findings in two cases. AJR Am J Roentgenol. 2003;181(4):1071-78. 

54. Greene CM, Reefhuis J, Tan C, et al. Epidemiologic investigations of bioterrorismrelated anthrax, New Jersey, 2001. Emerg Infect Dis. 2002;8(10):1048-55. 

55. Krol CM, Uszynski M, Dillon EH, Farhad M, Machnicki SC, Rothman LM. Case 

report: Dynamic CT features of inhaltional anthrax infection. AJR Am J Roentgenol. 

2002;178(5):1063-66. 

56. Holtz TH, Ackelsberg J, Kool JL, et al. Isolated case of bioterrorism-related 

inhalational anthrax, New York City, 2001. Emerg Infect Dis. 2003;9(6):689-96. 

57. Anonymous. Update: Investigation of bioterrorism-related inhalational anthrax - 

Connecticut, 2001. MMWR Morb Mortal Wkly Rep. 2001;50(47):1049-51. 

58. Griffith KS, Mead P, Armstrong GL, et al. Bioterrorism-related inhalational anthrax 

in an elderly woman, Connecticut, 2001. Emerg Infect Dis. 2003;9(6):681-88. 

59. Yorgancigil B, Sevuk E, Aydemir M, Demirci M, Doganay M. Anthrax meningitis. 

Turkish Journal of Medical Sciences. 1998;28:457-59. 

60. Yorgancigil B, Demirci M, Unlu M, Sevuk E, Doganay M. Anthrax meningitis: case 

report. Int J Infect Dis. 2001;5(4):220-21. 

61. Koshi G, Lalitha MK, Daniel J, Chacko A, Pulimood BM. Anthrax meningitis, a 

rare clinical entity. J Assoc Physicians India. 1981;29(1):59-62. 

62. Suffin SC, Carnes WH, Kaufmann AF. Inhalation anthrax in a home craftsman. 

Hum Pathol. 1978;9(5):594-7. 

63. Anonymous. CPSC warns about possible anthrax contamination in imported yarn; 

Release #76-011. Washington, D.C.: U.S. Consumer Product Safety Commission; 

Office of Information and Public Affairs; February 9, 1976, 1976. 

64. Severn M. A fatal case of pulmonary anthrax. Br Med J. 1976;1(6012):748. 

65. Vessal K, Yeganehdoust J, Dutz W, Kohout E. Radiological changes in inhalation 

anthrax. A report of radiological and pathological correlation in two cases. Clin 

Radiol. 1975;26(4):471-74. 

66. LaForce FM, Bumford FH. Epidemiological study of a fatal case of inhalation 

anthrax. Arch Environ Health. 1969;18:798-805. 

67. Enticknap JB. Anthrax due to working with imported dried bones. Med Sci Law. 
Appendix B: Adult Anthrax Case Reports Not Included in This Analysis, Continued 

B-6 

1967;7(3):136-37. 

68. Enticknap JB, Galbraith NS, Tomlinson AJ, Wlias-Jones TF. Pulmonary anthrax 

caused by contaminated sacks. Brit J Ind Med. 1968;25(1):72-74. 

69. Suic M, Knezevic J, Tomic M. A case of pulmonary anthrax. Lijec Vjesn. 

1966;88(12):1449-55. 

70. Kohout E, Sehat A, Ashraf M. Anthrax: A continuous problem in southwest Iran. 

Am J Med Sci. 1964;247:565-75. 

71. Anonymous. Inhalation anthrax - Delaware County, Pennsylvania. MMWR Morb 

Mortal Wkly Rep. 1961;10(28):2. 

72. Albrink WS. Pathogenesis of inhalation anthrax. Bacteriol Rev. 1961;25:268-73. 

73. Gold H. Treatment of anthrax. Fed Proc. 1967;26(5):1563-68. 

74. Albrink WS, Brooks SM, Biron RE, Kopel M. Human inhalation anthrax: a report 

of three cases. Am J Path. 1960;36:457-68. 

75. Brachman PS, Pagano JS, Albrink WS. Two cases of fatal inhalation anthrax, one 

associated with sarcoidosis. N Engl J Med. 1961;265(5):203-8. 

76. Anonymous. Anthrax. MMWR Morb Mortal Wkly Rep. 1957;6(20):2. 

77. Wright FJ, Ochjeng EC. A case of anthrax septicaemia resembling bubonic plague. 

East Afr Med J. 1954;31:516. 

78. Anonymous. Proceedings of the Symposium on Anthrax in Man. Philadelphia: 

Hospital of the University of Pennsylvania; October 8, 1954. 

79. Cowdery JS. Primary pulmonary anthrax with septicemia. Arch Pathol. 

1947;43:396-99. 

80. Gold H. Anthrax: a report of one hundred seventeen cases. AMA Arch Intern Med. 

1955;96:387-96. 

81. McKitterick JC, Pearson JC. Pneumonic anthrax in a child. Am J Dis Child. 

1929;38:1252-55. 

82. Bell HH. Pulmonary anthrax, with report of case. J Mo State Med Assoc. 

1924;21:407-9. 
Appendix B: Adult Anthrax Case Reports Not Included in This Analysis, Continued 

B-7 

Adult Primary Meningoencephalitis Cases 

83. Aguiah A. Un cas de meningite charbonneuse primitive chez un garcon de onze 

ans. Arch Med Enfants. 1928;31(11):676-680. 

84. Albayrak F, Memikoglu O, Kurt O, Cokca F, Birengel S, Tekeli E. A case of 

anthrax meningitis. Scand J Infect Dis. 2002;34(8):627-628. 

85. Al-Dulaimy SB, Al-Allaf GA. Anthrax meningitis. Trans R Soc Trop Med Hyg. 

1978;72(3):315. 

86. Bezzi C. Un raro caso di meningite da carbonchio ematico. G Batteriol Immunol. 

1952;6:353-360. 

87. Bharathmoorthy, Chakravarthy I, Swaminathan RP, Das AK, Malini G. 

Haemorrhagic meningitis due to bacillus anthrax (letter). J Assoc Physicians 

India. 1992;40(2):134-135. 

88. Bhat P, Mohan N. Human anthrax as seen in Southern India. Salisbury Med Bull. 

1990;68(Suppl):12. 

89. Bhat P, Pereira P, Mohan N. Primary anthrax meningitis - a case report. Neurol 

India. 1983;31(2):71-73. 

90. Chandramukhi A, Shankar P, Rao TV, Sundararajan S, Sathyanarayana Swamy 

HS. Acute leptomeningitis due to Bacillus antracis. A case report. Trop Geogr 

Med. 1983;35(1):79-82. 

91. Czyhlarz E. Beitrag zur lehre von der milzbrandmeningitis. Wien Klin 

Wochenschr. 1916;29(25):768-769. 

92. Drake DJ, Blair AW. Meningitic Anthrax. Cent Afr J Med. 1971;17(5):97-98. 

93. George S, Mathai D, Balraj V, Lalitha MK, Jacob John T. An outbreak of anthrax 

meningoencephalitis. Trans R Soc Trop Med Hyg. 1994;88(2):206-207. 

94. Gross H, Plate H. Milzbrandbacillen-Meningitis. Klin Wochenschr. 

1940;19(40):1036-1037. 

95. Jones HW. Landry's paralysis with report of a case. Med Rec. 1913;84:335-337. 

96. Kanungo R, Kumar A, Bhattacharya S, Dutta TK, Das AK, Badrinath S. Problem 

of timely diagnosis in anthrax meningitis. J Assoc Phys India. 2002;50:913-915. 
Appendix B: Adult Anthrax Case Reports Not Included in This Analysis, Continued 

B-8 

97. Kanungo R, Sujatha S, Das AK, Rao RS. Anthrax meningitis - a clinical enigma. 

Indian J Med Microbiol. 1990;6:149-151. 

98. Lalitha MK, Anandi V, Walter NM, et al. Unusual forms of anthrax - a clinical 

problem. Salisbury Med Bull. 1990;68(Suppl):38-40. 

99. Marandian MH, Kamali A. [Anthrax meningitis: an ostensibly primary case]. 

Nouv Presse Med. 1981;10(21):1747-1748. 

100. Mitchell GF. Meningeal anthrax. BMJ. 1921;2:508. 

101. Rangel RA, Gonzalez DA. Bacillus anthracis meningitis. Neurology. 

1975;25(6):525-530. 

102. Reece RJ. Anthrax: simulating cerebro-spinal fever. Lancet. 1917;1:406-410. 

103. Rozenier LA. [Internal forms of the malignant anthrax]. Klin Med (Mosk). 

1944;20(10-11):56-63. 

104. Sakon H, Accart R. Un cas de meningite charbonneuse suraigue. Maroc Med. 

1938;18:342-344. 

105. Sirol J, Delpy J, Guard O. Une epidemie de charbon humain. A propos de 25 cas 

observes a l'Hopital de Fort Lamy, Tchad. Presse Med. 1971;79(37):1635-1638. 

106. Slatineanu A, Balteanu I, Franche M. Doua cazuri de meningo-encefalita 

carbunoasa. Miscarea Med Romana. 1939:12-18. 

107. Urechia CI, Retezeanu A, Muller M. Les complications nerveuses du charbon 

(encephalo-meningo-myelite). Monatsschr Psychiatr Neurol. 1940;102:336-352. 

108. Vita A, Secu A, Cuciureanu G, Leibovici M, Bejenariu C, Cutu G. 

[Considerations on 3 cases of meningo-encephalitis due to anthrax bacilli]. Viata 

Med. 1960(8):661-664. 

109. Vita A, Secu A, Cuciureanu G, Leibovici M, Bejenariu C, Cutu G. Considerations 

on 3 cases of meningo-encephalitis due to anthrax bacilli. Rum Med Rev. 

1961;5:36-39. 
Appendix B: Adult Anthrax Case Reports Not Included in This Analysis, 

Continued 

B-9 

Adult Atypical Cases 

110. Inda FF, Natin I, Da Rin C. El carbunclo por inhalacion. Sem Med. 

1943;50(1):754-761. 

111. Inda FF, Natin I, Guiliano A. El diagnostico del carbunclo por inhalacion. 

Sem Med. 1947;54:38-42. 

112. Pasha ZN. Anthrax in the nasal cavity. Br Med J. 1921;2:446. 

113. Mathias, Blobmke. Beitrage zur pathologie und klinik des menschlichen 

milzbrandes. Dtsch Med Wochenschr. 1914;40(42):1860-1862. 

114. Parsons JG. Abscess of the nasal septum, probably due to anthrax infection. 

JAMA. 1908;51:1697. 

115. Risel W. Ein beitrag zur pathologie des milzbrandes beim menschen. Z Hyg 

Infektionskr (Leipzig). 1903;42 (32):381-418. 

116. Sirol J, Delpy J, Guard O. Une epidemie de charbon humain. A propos de 25 

cas observes a l'Hopital de Fort Lamy, Tchad. Presse Med. 

1971;79(37):1635-1638. 

117. Ker WG. Clinical notes. East Afr Med J. 1944;21:93-96. 

118. Vaccarezza RF. Charbon primitif du pharynx. Presse Med. Dec 

1939(94):1642-1644. 

119. Glas E. Milzbrand des kehlkopfes. Munch Med Wochenschr. 

1906;53(11):496-498. 

120. Glas E. Milzbrand (Anthrax). In: Denker A, Kahler O, eds. Handbuch der 

Hals-Nasen-Ohrenheilkunde. Vol IV. Berlin: Springer-Verlag; 1928:398-406.
Appendix C: Peer Reviewers 

Peer Reviewer Organizational Affiliation 

Ann M. Arvin, MD 

 

Lucile Salter Packard Professor of Pediatrics 

Associate Dean of Research 

Professor of Microbiology & Immunology 

Stanford University 

Chief, Pediatric Infectious Diseases 

Krista M. Scardina, Pharm.D. Public Health Analyst; Health Resources and Services 

Administration; Healthcare Systems Bureau; Division of 

Healthcare Preparedness; National Bioterrorism Hospital 

Preparedness Program 

Nathaniel Hupert, M.D., M.P.H. Assistant Professor of Medicine and Public Health 

Weill Medical College, Department of Public Health 

Gregory Moran, M.D. Clinical Professor of Medicine, UCLA School of Medicine 

Department of Emergency Medicine and Division of Infectious 

Diseases, Olive View-UCLA Medical Center 

Mike Osterholm, Ph.D. Director of the Center for Infectious Disease Research and Policy 

(CIDRAP), Associate Director of the Department of Homeland 

Security's National Center for Food Protection and Defense 

(NCFPD), and Professor of Public Health, University of 

Minnesota 

Irwin Redlener, M.D. 

 

Professor of Clinical Public Health and Pediatrics 

Associate Dean 

& Director, The National Center for Disaster Preparedness 

Columbia University Mailman School of Public Health 

Dean Wilkening, Ph.D. Science Director, Center for International Security and 

Cooperation, Stanford University