Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States. (Research).From October 4 to November 2, 2001, the first 10 confirmed cases of inhalational anthrax caused by intentional release of Bacillus anthracis were identified in the United States. Epidemiologic investigation indicated that the outbreak, in the District of Columbia District of Columbia, federal district (2000 pop. 572,059, a 5.7% decrease in population since the 1990 census), 69 sq mi (179 sq km), on the east bank of the Potomac River, coextensive with the city of Washington, D.C. (the capital of the United States). , Florida, New Jersey, and New York, resulted from intentional delivery of B. anthracis spores through mailed letters or packages. We describe the clinical presentation and course of these cases of bioterrorism-related inhalational anthrax. The median age of patients was 56 years (range 43 to 73 years), 70% were male, and except for one, all were known or believed to have processed, handled, or received letters containing B. anthracis spores. The median incubation period from the time of exposure to onset of symptoms, when known (n=6), was 4 days (range 4-6 days). Symptoms at initial presentation included fever or chills (n=10), sweats (n=7), fatigue or malaise (n=10), minimal or nonproductive cough (n=9), dyspnea (n=8), and nausea or vomiting (n=9). The median white blood cell count white blood cell count,
n a diagnostic clinical laboratory test to determine the number and types of leukocytes present in a measured sample of blood. Overall the normal number of leukocytes ranges from 5000 to 10,000/mm3. was 9.8 X [10.sup.3] /[mm.sup.3] (range 7.5 to 13.3), often with increased neutrophils and band forms. Nine patients had elevated serum transaminase transaminase /trans·am·i·nase/ (-am´i-nas) aminotransferase.
See aminotransferase. levels, and six were hypoxic hypoxic
a state of hypoxia.
hypoxic cell sensitizers
compounds that selectively sensitize hypoxic tumor cells to the effects of radiation. . All 10 patients had abnormal chest X-rays; abnormalities included infiltrates (n=7), pleural effusion (n=8), and mediastinal mediastinal /me·di·as·ti·nal/ (-as-ti´n'l) of or pertaining to the mediastinum.
of or pertaining to the mediastinum. widening (seven patients). Computed tomography of the chest was performed on eight patients, and mediastinal lymphadenopathy lymphadenopathy /lym·phad·e·nop·a·thy/ (-op´ah-the) disease of the lymph nodes.
angioimmunoblastic lymphadenopathy , angioimmunoblastic lymphadenopathy with dysproteinemia was present in seven. With multidrug antibiotic regimens and supportive care, survival of patients (60%) was markedly higher (<15%) than previously reported.
Historically, human anthrax in its various forms has been a disease of those with close contact to animals or animal products contaminated with Bacillus anthracis spores. In the mid-1800s, inhalational anthrax related to the textile industry became known as woolsorters' disease (in England) (1) and ragpickers' disease (in Germany and Austria) because of the frequency of infection in mill workers exposed to imported animal fibers contaminated with B. anthracis spores. In the early 1900s, human cases of inhalational anthrax occurred in the United States in conjunction with the textile and tanning industries. In the last part of the 20th century, with improved industrial hygiene practices and restrictions on imported animal products, the number of cases fell dramatically (1,2); however, death rates remained high (>85%) (1,3). In 1979, in Sverdlovsk, former Soviet Union, an apparent aerosol release of B. anthracis spores from a military facility resulted in the largest outbreak of inhalational anthrax in the 20th century (3).
Before October 2001, the last case of inhalational anthrax in the United States had occurred in 1976 (1,4). Identification of inhalational anthrax in a journalist in Florida on October 4, 2001, marked the beginning of the first confirmed outbreak associated with intentional anthrax release in the United States (5,6). We describe the clinical presentation of the first 10 cases of this bioterrorism-related outbreak.
From October 4 to November 2, 2001, the Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. (CDC See Control Data, century date change and Back Orifice.
CDC - Control Data Corporation ) and state and local public health authorities reported 10 confirmed cases of inhalational anthrax and 12 confirmed or suspected cases of cutaneous anthrax in persons who worked in the District of Columbia, Florida, New Jersey, and New York (6,7). Epidemiologic investigation indicated that the outbreak resulted from intentional delivery of B. anthracis spores through mailed letters or packages.
Of the 10 inhalational cases, 7 occurred in postal employees in New Jersey and the District of Columbia who were likely exposed to letters known to be contaminated with B. anthracis spores. Two cases were in employees of a media company in Florida: one is believed to have received contaminated mail, the other to have sorted and distributed that mail. Case 10 was in a resident of New York, and the nature of her exposure to B. anthracis is currently unknown.
In the course of the US Public Health Service response to the outbreak, CDC, in conjunction with state and local health departments, collected clinical data from patients with confirmed inhalational anthrax as defined by the CDC surveillance case definition (8). Data were collected through a variety of methods, including interviews with patients and family members, physical examinations of patients, discussions with clinicians, reviews of medical records, and analyses of clinical and pathologic specimens.
Presumptive isolation of B. anthracis in these patients was confirmed by gamma phage lysis, presence of a capsule, detection of capsule and cell-wall antigens by direct fluorescent antibody Direct fluorescent antibody (DFA or dFA) is a laboratory test that uses antibodies tagged with fluorescent dye to detect the presence of microorganisms. This is the main test used to detect rabies in animals and requires the examination of brain tissue. , and B. anthracis-specific polymerase chain reaction polymerase chain reaction (pŏl`ĭmərās') (PCR), laboratory process in which a particular DNA segment from a mixture of DNA chains is rapidly replicated, producing a large, readily analyzed sample of a piece of DNA; the process is (PCR PCR polymerase chain reaction.
polymerase chain reaction
Polymerase chain reaction (PCR) ). All isolates were confirmed by state and other laboratory facilities of the National Bioterrorism Laboratory Response Network and by the laboratories of the National Center for Infectious Diseases (NCID NCID National Center for Infectious Diseases (US CDC)
NCID Non-Cooperative Identification
NCID Net-Centric Implementation Document (US DoD) ), CDC. Other tests performed at NCID for confirming the diagnosis of inhalational anthrax (8) included immunohistochemical testing of clinical specimens by using B. anthracis capsule and cell-wall antibody, B. anthracis-specific PCR, and serologic detection of immunoglobulin (Ig) G to B. anthracis protective antigen (PA).
On October 2, 2001, a 63-year-old Caucasian photo editor working for a Florida newspaper awoke early with nausea, vomiting, and confusion and was taken to a local emergency room for evaluation. His illness, which started on September 27 during a trip to North Carolina, was characterized by malaise, fatigue, fever, chills, anorexia, and sweats. No history of headache, cough, chest pain, myalgias, dyspnea, abdominal pain, diarrhea, or skin lesions was reported. Past medical history included hypertension, cardiovascular disease, and gout. He did not smoke. On admission, the patient was alert and interactive but spoke nonsensically. Temperature was 39.2 [degrees] C, heart rate 109/min; blood pressure and respiratory rate were normal. Initial pulmonary, heart, and abdominal examinations were reported as normal. No nuchal nuchal (nyōōˑ·kl),
adj pertaining to the posterior or nape of the neck. rigidity was observed. He was not oriented to person, place, or time. Admission laboratory values included a normal total white blood cell (WBC WBC white blood cell; see leukocyte.
white blood cell
n stands for white
cell. ) count, but the platelet count was low. Serum chemistries were normal, except for borderline hyponatremia Hyponatremia Definition
The normal concentration of sodium in the blood plasma is 136-145 mM. Hyponatremia occurs when sodium falls below 130 mM. Plasma sodium levels of 125 mM or less are dangerous and can result in seizures and coma. and elevated total bilirubin Bilirubin
The predominant orange pigment of bile. It is the major metabolic breakdown product of heme, the prosthetic group of hemoglobin in red blood cells, and other chromoproteins such as myoglobin, cytochrome, and catalase. . He had mild metabolic acidosis (Table 1). A chest X-ray showed a prominent superior mediastinum and a possible small left pleural effusion (Figure 1). Cerebrospinal fluid (CSF Cerebrospinal Fluid (CSF) Analysis Definition
Cerebrospinal fluid (CSF) analysis is a laboratory test to examine a sample of the fluid surrounding the brain and spinal cord. ) analysis showed WBC count 4,750/[micro]L (81% neutrophils), red blood cell count red blood cell count,
n the number of red blood cells (erthrocytes) in 1 mm3 of blood; a useful diagnostic tool in the determination of several kinds of anemia. See also mean corpuscular hemoglobin. 1,375/[micro]L, glucose 57 mg/dL (serum glucose 174 mg/dL), and protein 666 mg/dL. Microscopy examination of the CSF showed many gram-positive bacilli (Figure 2). B. anthracis was isolated from CSF after 7 hours of incubation and from blood cultures within 24 hours of incubation. The patient was admitted to the hospital with a diagnosis of meningitis. After a single dose of cefotaxime, he was started on multiple antibiotics, including ceftazidime, gentamicin gentamicin /gen·ta·mi·cin/ (jen?tah-mi´sin) an aminoglycoside antibiotic complex isolated from bacteria of the genus Micromonospora, , metronidazole metronidazole /met·ro·ni·da·zole/ (-ni´dah-zol) an antiprotozoal and antibacterial effective against obligate anaerobes; used as the base or the hydrochloride salt. It is also used as a topical treatment for rosacea. , doxycycline doxycycline /doxy·cy·cline/ (dok?se-si´klen) a semisynthetic broad-spectrum tetracycline antibiotic, active against a wide range of gram-positive and gram-negative organisms; used also as d. calcium and d. hyclate. , ampicillin ampicillin (ăm'pĭsĭl`ĭn), a penicillin-type antibiotic that is effective against both gram-negative microorganisms and gram-positive microorganisms such as Escherichia coli. , and trimethoprim-sulfamethoxazole. Shortly after admission, he had generalized seizures and was intubated for airway protection. On hospital day 2, penicillin G, levofloxacin, and clindamycin were begun; ampicillin, ceftazidime, and trimethoprim-sulfamethoxazole were discontinued. He remained febrile and became unresponsive to deep stimuli. His condition progressively deteriorated, with hypotension and worsening renal insufficiency. The patient died on October 5. Autopsy findings included hemorrhagic Hemorrhagic
A condition resulting in massive, difficult-to-control bleeding.
Mentioned in: Hantavirus Infections
pertaining to or characterized by hemorrhage. mediastinal lymphadenitis Lymphadenitis Definition
Lymphadenitis is the inflammation of a lymph node. It is often a complication of a bacterial infection of a wound, although it can also be caused by viruses or other disease agents. , and immunohistochemical staining showed disseminated B. anthracis in multiple organs.
[FIGURES 1-2 OMITTED]
On September 24, a 73-year-old Hispanic man, the newspaper mailroom clerk who delivered mail to the patient in Case 1, had onset of fatigue. On September 28, nonproductive cough, intermittent fever, rhinorrhea, and conjunctivitis conjunctivitis (kənjəngtəvī`təs), inflammation or infection of the mucosal membrane that covers the eyeball and lines the eyelid, usually acute, caused by a virus or, less often, by a bacillus, an allergic reaction, or an developed. From September 28 to October 1, he had gradual progression of cough, marked worsening of fatigue with lethargy, onset of exertional dyspnea, fever, and sweats. He had mild abdominal pain associated with vomiting, and his co-workers and family noted intermittent periods of confusion. He had no underlying chronic illnesses, with the exception of a transient ischemic attack Transient Ischemic Attack Definition
A transient ischemic attack, or TIA, is often described as a mini-stroke. Unlike a stroke, however, the symptoms can disappear within a few minutes. in August 2001. He did not smoke. He was admitted to the hospital on October 1. Temperature was 38.5 [degrees] C, heart rate 109/min, respiratory rate 20/ min, and blood pressure 108/61 mm Hg. He had bilateral conjunctival con·junc·ti·val
Relating to the conjunctiva.
pertaining to or emanating from conjunctiva.
congenital conjunctival membrane injection and bilateral pulmonary rhonchi Rhonchi is the "coarse rattling sound somewhat like snoring, usually caused by secretion in bronchial airways". Rhonchi is the plural form of the singular word "rhonchus". . Examination, including assessment of neurologic function, was otherwise unremarkable. No skin lesions were observed. Admission laboratory results included normal WBC count and serum chemistries, except for hypoalbuminemia, elevated hepatic transaminases, borderline hyponatremia, and increased creatinine. Arterial blood gas arterial blood gas Critical care Analysis of arterial blood for O2, CO2, bicarbonate content, and pH, which reflects the functional effectiveness of lung function and to monitor respiratory therapy Ref range pO2 values showed hypoxia hypoxia
Condition in which tissues are starved of oxygen. The extreme is anoxia (absence of oxygen). There are four types: hypoxemic, from low blood oxygen content (e.g., in altitude sickness); anemic, from low blood oxygen-carrying capacity (e.g. (Table 1). Blood cultures obtained on hospital day 2, after initiation of antibiotics, showed no growth. A chest X-ray showed left upper and lower lobe infiltrates consistent with pneumonia and a small left pleural effusion (Figure 3).
[FIGURE 3 OMITTED]
No mediastinal widening was observed. The patient was initially given intravenous azithromycin; cefotaxime and ciprofloxacin were subsequently added. A nasal swab obtained on October 5 grew B. anthracis. Computed tomography (CT) of the chest showed bilateral effusions and multilobar pulmonary consolidation but no significant mediastinal lymphadenopathy (Figure 4). A left thoracentesis yielded serosanguinous fluid (Table 1) positive for B. anthracis DNA DNA: see nucleic acid.
or deoxyribonucleic acid
One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. by PCR. Bronchoscopy Bronchoscopy Definition
Bronchoscopy is a procedure in which a cylindrical fiberoptic scope is inserted into the airways. This scope contains a viewing device that allows the visual examination of the lower airways. showed bloody secretions in the right lower lobe and left lung, with severe mucosal hyperemia hyperemia /hy·per·emia/ (-e´me-ah) engorgement; an excess of blood in a part.hypere´mic
active hyperemia , arterial hyperemia that due to local or general relaxation of arterioles. , mottling mottling /mot·tling/ (-ling) a condition of spotting with patches of color. , and inflammation. Bacterial cultures of bronchial washings and pleural fluid did not grow. A transbronchial biopsy showed B. anthracis capsule and cell-wall antigens by immunohistochemical staining. Tests for Legionella Legionella /Le·gion·el·la/ (le?jah-nel´ah) a genus of gram-negative, aerobic, rod-shaped bacteria (family Legionellaceae), normal inhabitants of lakes, streams, and moist soil; they have often been isolated from cooling-tower water, spp., acid-fast bacteria, Pneumocystis carinii, Chlamydia spp., Leptospira, and Hantavirus hantavirus, any of a genus (Hantavirus) of single-stranded RNA viruses that are carried by rodents and transmitted to humans when they inhale vapors from contaminated rodent urine, saliva, or feces. There are many strains of hantavirus. and other viral pathogens were negative. The hospital course included an episode of supraventricular tachycardia with hypotension, maximum WBC count 26,800/ [mm.sup.3], and recurrent left pleural effusion that required repeat thoracentesis and placement of a chest tube. The pleural fluid from the second thoracentesis was positive for B. anthracis DNA by PCR. A pleural fluid cytology preparation and pleural biopsy showed B. anthracis capsule and cell-wall antigens by immustaining. In addition, serial serum samples demonstrated a >4-fold rise in levels of serum antibody (IgG) to the PA component of the anthrax toxins by enzyme-linked immunosorbent assay enzyme-linked immunosorbent assay
Enzyme-linked immunosorbent assay (ELISA)
A diagnostic blood test used to screen patients for AIDS or other viruses. (ELISA ELISA (e-li´sah) Enzyme-Linked Immuno-Sorbent Assay; any enzyme immunoassay using an enzyme-labeled immunoreactant and an immunosorbent.
n. ). The patient's condition gradually improved, and he was discharged from the hospital October 23 on oral ciprofloxacin.
[FIGURE 4 OMITTED]
On October 16, a 56-year-old African-American man, a US Postal Service mail sorter, noted low-grade fever, chills, sore throat, headache, and malaise. This was followed by minimal dry cough, chest heaviness, shortness of breath Shortness of Breath Definition
Shortness of breath, or dyspnea, is a feeling of difficult or labored breathing that is out of proportion to the patient's level of physical activity. , night sweats, nausea, and vomiting. On October 19, when he arrived at a local hospital, he was afebrile afebrile /afe·brile/ (a-feb´ril) without fever.
afebrile adjective Feverless and normotensive normotensive /nor·mo·ten·sive/ (-ten´siv)
1. characterized by normal tone, tension, or pressure, as by normal blood pressure.
2. a person with normal blood pressure. . Heart rate was 110/min, and he was not tachypneic. He was in no acute distress but had decreased breath sounds and rhonchi at the left base. No skin lesions were observed. His past medical history was unremarkable, and he did not smoke. Total WBC count was normal, but there was a slight left shift in the differential. Hepatic transaminase levels and bilirubin were elevated. Serum albumin was decreased, but serum chemistries and renal function were normal. Arterial blood gas values showed adequate oxygenation oxygenation /ox·y·gen·a·tion/ (ok?si-je-na´shun)
1. the act or process of adding oxygen.
2. the result of having oxygen added. (Table 1). A chest X-ray showed a widened mediastinum (especially in the right paratracheal region), bilateral hilar hi·lar
Of or relating to a hilum. masses, bilateral pleural effusions, and a small right lower lobe air space opacity. CT of the chest showed diffuse mediastinal edema edema (ĭdē`mə), abnormal accumulation of fluid in the body tissues or in the body cavities causing swelling or distention of the affected parts. ; marked paratracheal, subcarinal, hilar, and azygo-esophageal recess adenopathy (the largest node measuring 4.2 cm in diameter); and bilateral moderate pleural effusions. Within 11 hours, admission blood cultures grew B. anthracis. Ciprofloxacin, rifampin rifampin (rĭfăm`pĭn), antibiotic used in the treatment of tuberculosis. It is also used to eliminate the meningococcus microorganism from carriers and to treat leprosy, or Hansen's disease. , and clindamycin were initiated. On October 21, the patient had respiratory distress, which was treated with diuretics, systemic corticosteroids, and a therapeutic thoracentesis. During the course of hospitalization, the pleural effusion reaccumulated, necessitating two additional thoracenteses. All three pleural fluid specimens were hemorrhagic. The patient did not require a chest tube. Hematemesis hematemesis /he·ma·tem·e·sis/ (he?mah-tem´e-sis) the vomiting of blood.
The vomiting of blood. developed, and several shallow gastric ulcers were noted on upper endoscopy. On October 28, the patient had signs of hemolytic anemia and thrombocytopenia Thrombocytopenia Definition
Thrombocytopenia is an abnormal drop in the number of blood cells involved in forming blood clots. These cells are called platelets. , which was treated with plasmapheresis plasmapheresis, see apheresis. . Hematologic hematological, hematologic
pertaining to or emanating from blood cells.
total and differential white cell counts, hematocrit estimation, erythrocyte count. values subsequently improved, and the patient remains hospitalized in stable condition.
On October 16, a 56-year-old African-American man, a US Postal Service worker, noted mild headache that was constant and global but not associated with visual changes, stiff neck, or other neurologic symptoms. Over the following 3 days, the headache worsened and was accompanied by low-grade fever, chills, sore throat, myalgias, nausea, malaise, drenching drenching
farmer's term for the administration of medicines as solutions or suspensions in water by mouth with a drench bottle, gun or funnel.
to be included in a bridle as a bit. sweats, intermittent blurred vision, and photophobia photophobia /pho·to·pho·bia/ (-fo´be-ah) abnormal visual intolerance to light.photopho´bic
1. . A mild dry cough, dyspnea on exertion dyspnea on exertion Cardiology Shortness of breath which occurs with effort, often a sign of heart failure or ischemia , and pleuritic pleu·rit·ic
Of or relating to pleurisy.
pertaining to or emanating from pleurisy. See also pleural.
pleuritic ridge chest pain developed. When he arrived at the hospital on October 20, he was afebrile and normotensive, pulse was 127/min, and respiratory rate 20/min. He was in no acute distress, and physical examination was unremarkable, except for decreased breath sounds at both bases. His past medical history was unremarkable, and he did not smoke. Admission laboratory results were normal, except for elevated bilirubin and hepatic enzymes, low albumin, and hypoxia (Table 1). A noncontrasted head CT was normal, and CSF exhibited 4 WBC/[micro]L (all lymphocytes), 20 RBC/[micro]L, with normal glucose and protein. No organisms were seen on Gram stain of the CSF, and CSF culture did not grow. An anteroposterior anteroposterior /an·tero·pos·te·ri·or/ (-pos-ter´e-er) directed from the front toward the back.
adj. Abbr. AP
1. Relating to both front and back. chest X-ray showed a widened mediastinum, bilateral hilar masses, right pleural effusion, and bilateral perihilar air space disease. A noncontrasted chest CT scan showed diffuse mediastinal edema; bilateral pleural effusions; bibasilar air space disease; and marked paratracheal, subcarinal, hilar, and azygo-esophageal recess adenopathy. Admission blood cultures grew B. anthracis within 15 hours. Ciprofloxacin, rifampin, and clindamycin were begun. On October 22, signs of worsening respiratory distress developed, and on October 23, the patient underwent therapeutic thoracentesis, which yielded bloody pleural fluid, after which his condition improved. He also received systemic corticosteroids for bronchospasm bronchospasm /bron·cho·spasm/ (brong´ko-spazm) bronchial spasm; spasmodic contraction of the smooth muscle of the bronchi, as in asthma.
n. . He required a second thoracentesis and was discharged from the hospital on November 9.
On October 16, a 55-year-old African-American man, a District of Columbia US Postal Service employee, became ill. He had fever, intermittent diaphoresis diaphoresis /di·a·pho·re·sis/ (-fah-re´sis) sweating, especially of a profuse type.
Perspiration, especially when copious and medically induced. , myalgias, and cough productive of green sputum but no shortness of breath, chest discomfort, gastrointestinal symptoms, or headache. When he visited his primary-care provider on October 18, he had temperature of 38.9 [degrees] C, normal heart rate and blood pressure, and respiratory rate of 24/min. He had no other notable examination findings, but WBC count was slightly elevated (Table 1). His past medical history included diabetes mellitus and sarcoidosis Sarcoidosis Definition
Sarcoidosis is a disease which can affect many organs within the body. It causes the development of granulomas. Granulomas are masses resembling little tumors. They are made up of clumps of cells from the immune system. . He did not smoke. No chest X-ray was performed. He was sent home with a diagnosis of a viral syndrome; no antibiotics were prescribed. On October 21, he arrived at the emergency department with worsening symptoms, including chest tightness, fatigue, chills, myalgias, nausea, vomiting, and shortness of breath. Temperature was 38.9 [degrees] C, pulse 93 to 150/rain and irregular, respiratory rate 20/min, and blood pressure 119/73 mm Hg. Signs of respiratory distress were observed. Examination findings included rales at the right base with diffuse wheezing Wheezing Definition
Wheezing is a high-pitched whistling sound associated with labored breathing.
Wheezing occurs when a child or adult tries to breathe deeply through air passages that are narrowed or filled with mucus as a and tachycardia. WBC count was 18,800/[mm.sup.3] with a differential of 73% segmented neutrophils, 6% bands, 11% lymphocytes, and 8% monocytes monocytes,
n.pl the largest of the white blood cells. They have one nucleus and a large amount of grayish-blue cytoplasm. Develop into macrophages and both consume foreign material and alert T cells to its presence. . Hematocrit Hematocrit Definition
The hematocrit measures how much space in the blood is occupied by red blood cells. It is useful when evaluating a person for anemia.
Blood is made up of red and white blood cells, and plasma. was 55%, and platelets were 141,000/ [mm.sup.3]. Sodium was 130 mmol/L, potassium 5.3 mmol/L, chloride 99 mmol/L, and bicarbonate 14 mmol/L, with an anion gap of 17. Creatinine was 1.6 mg/dL, and glucose was 425 mg/dL. Aspartate aminotransferase (AST (AST Computer, Irvine, CA) A PC manufacturer founded in 1980 by Albert Wong, Safi Quershey and Tom Yuen (A, S and T). It offered a complete line of PCs that sold through its dealer channel. ) was 76 IU/L and alanine aminotransferase (ALT) was 77 IU/L. Coagulation coagulation (kōăg'ylā`shən), the collecting into a mass of minute particles of a solid dispersed throughout a liquid (a sol), usually followed by the precipitation or studies were normal. Arterial pH was 7.42, PaC[O.sub.2] 25 mm Hg, Pa[O.sub.2] 66 mm Hg, and [O.sub.2] saturation 93% on 2 L of [O.sub.2]/min by nasal cannula. A chest X-ray showed right hilar and peritracheal soft tissue fullness with right middle and lower lobe infiltrates compatible with pneumonia and right pleural effusion. An electrocardiogram electrocardiogram /elec·tro·car·dio·gram/ (-kahr´de-o-gram?) a graphic tracing of the variations in electrical potential caused by the excitation of the heart muscle and detected at the body surface. showed atrial fibrillation. The patient was intubated, ventilated ven·ti·late
tr.v. ven·ti·lat·ed, ven·ti·lat·ing, ven·ti·lates
1. To admit fresh air into (a mine, for example) to replace stale or noxious air.
2. , and administered levofloxacin, diltiazem, and insulin. Later on the day of admission, the patient became hemodynamically unstable, had cardiac arrest, and died. Blood cultures grew B. anthracis. Autopsy findings included hemorrhagic mediastinal lymphadenitis, and immunohistochemical staining showed evidence of disseminated B. anthracis.
On October 16, a 47-year-old African-American man, a US Postal Service employee who worked at the same District of Columbia mail distribution center associated with cases 3, 4, and 5, had mild nonproductive cough, nausea, vomiting, and stomach cramps. On October 20, the patient had a syncopal syn·co·pal
Of or relating to syncope. episode at church but did not seek medical attention. Early in the morning of October 21, he arrived at an emergency department complaining of vomiting and profuse sweating. His past medical history included asthma and renal calculi. Therapy for asthma had not recently included corticosteroids. He was afebrile and had orthostatic hypotension. WBC count was slightly elevated, but he had normal serum chemistries and coagulation values. Serum glutamic pyruvic transaminase serum glutamic pyruvic transaminase (sirˑ· (SGPT SGPT serum glutamic-pyruvic transaminase; see alanine transaminase.
Serum pyruvate aminotransferase; an enzyme in serum and body tissues that catalyzes the transfer of amino acid groups from ) was slightly elevated (Table 1). A chest X-ray was initially read as normal, but later review noted an ill-defined area of increased density due to infiltrate or mass in the right suprahilar region. The patient was discharged after receiving intravenous hydration hydration /hy·dra·tion/ (hi-dra´shun) the absorption of or combination with water.
1. The addition of water to a chemical molecule without hydrolysis.
2. . On the morning of October 22, he visited the emergency department again, reporting myalgias, chills, dyspnea, continued vomiting, and another syncopal episode. His temperature was 35.6 [degrees] C, blood pressure 76/48 mm Hg, heart rate 152/ rain, and respiratory rate 32/min. He was ill-appearing with mottled skin that was cool to the touch, and he was in respiratory distress. He had bilateral wheezing, tachycardia, and mildly distended distended Medtalk Enlarged, bloated. Cf Nondistended. abdomen with absent bowel sounds. WBC count was 31,200/[mm.sup.3] with a differential of 78% segmented neutrophils, 2% bands, 14% lymphocytes and 3% monocytes. Sodium was 148 mmol/L, bicarbonate 18 mmol/L, anion gap 21, and creatinine 2.8 mg/dL. Serum glutamic oxalacetic transaminase Noun 1. glutamic oxalacetic transaminase - an enzyme involved in transamination
glutamic oxaloacetic transaminase
aminopherase, aminotransferase, transaminase - a class of transferases that catalyze transamination (that transfer an amino group from an amino (SGOT SGOT serum glutamic-oxaloacetic transaminase; see aspartate transaminase.
Serum glutamic aminotransferase; an enzyme that catalyzes the transfer of the amino group from glutamic acid to oxaloacetic acid ) was 47 IU/L, SGPT 33 IU/L, and alkaline phosphatase 197 IU/L. Prothrombin time was 13.3 seconds and partial thromboplastin time Partial Thromboplastin Time Definition
The partial thromboplastin time (PTT) test is a blood test that is done to investigate bleeding disorders and to monitor patients taking an anticlotting drug (heparin). was 40 seconds. Penicillin, ceftriaxone ceftriaxone /cef·tri·ax·one/ (cef?tri-ak´son) a semisynthetic, ß–resistant, third-generation cephalosporin effective against a wide range of gram-positive and gram-negative bacteria, used as the sodium salt. , rifampin, and levofloxacin were begun. Respiratory distress developed, which required endotracheal intubation and mechanical ventilation. Soon thereafter signs consistent with peritonitis peritonitis (pĕr'ĭtənī`tĭs), acute or chronic inflammation of the peritoneum, the membrane that lines the abdominal cavity and surrounds the internal organs. were observed. Arterial pH was 7.13, PaC[O.sub.2] 37 mm Hg, Pa[O.sub.2] 106 mm Hg, and oxygen saturation 95% after intubation intubation /in·tu·ba·tion/ (in?too-ba´shun) the insertion of a tube into a body canal or hollow organ, as into the trachea.
endotracheal intubation on 100% Fi[O.sub.2]. A chest X-ray showed bilateral lung infiltrates concentrated within perihilar and infrahilar regions without pleural effusions. Chest and abdominal CT scans with intravenous contrast noted large bilateral pleural effusions, perihilar and suprahilar infiltrates, mediastinal edema, pneumomediastinum, ascites Ascites Definition
Ascites is an abnormal accumulation of fluid in the abdomen.
Rapidly developing (acute) ascites can occur as a complication of trauma, perforated ulcer, appendicitis, or inflammation of the colon or other , air in the portal venous system This article discusses portal venous systems in general. For the system involving the liver, see Hepatic portal system.
In the circulatory system of animals, a portal venous system occurs when a capillary bed drains into another capillary bed through veins. , mesenteric mesenteric /mes·en·ter·ic/ (-ter´ik) pertaining to the mesentery.
pertaining to or emanating from the mesentery. edema, diffuse small bowel edema, and small collections of intramural intramural /in·tra·mu·ral/ (-mu´r'l) within the wall of an organ.
Occurring or situated within the walls of a cavity or organ. air involving several parts of the jejunum jejunum: see intestine. . CT of the head was normal. The patient died within 6 hours of admission. Gram-positive bacilli were visible on the buffy coat blood smear, and blood cultures grew B. anthracis within 18 hours. Postmortem postmortem /post·mor·tem/ (post-mort´im) performed or occurring after death.
Relating to or occurring during the period after death.
See autopsy. findings included prominent hemorrhagic mediastinal lymphadenitis and evidence of systemic B. anthracis infection by histopathologic and immunohistochemical tests.
On the evening of October 22, a 59-year-old Caucasian man, contract employee at a U.S. State Department mail sorting facility that received mail from the District of Columbia postal facility associated with cases 3, 4, 5, and 6, became ill. He had drenching sweats, followed over the next 2 days by fatigue, severe myalgias, subjective fever, chills, headache, nausea, vomiting, abdominal pain, cough with scant white sputum, and substernal chest pain. He had no dyspnea or diarrhea. When he arrived at a local emergency room on October 24, temperature was 38.2 [degrees] C, heart rate 116/min, and respiratory rate and blood pressure were normal. A complete blood count was normal, and serum electrolytes showed hyponatremia and hypokalemia Hypokalemia Definition
Hypokalemia is a condition of below normal levels of potassium in the blood serum. Potassium, a necessary electrolyte, facilitates nerve impulse conduction and the contraction of skeletal and smooth muscles, including the heart. (Table 1). His past medical history was unremarkable, and he did not smoke. A chest X-ray was initially reported as normal. The patient was thought to have a viral syndrome and was discharged, but blood cultures were obtained and ciprofloxacin was prescribed. He took one dose that night, but vomiting, fatigue, and headache worsened. He also reported transient distortion in his left visual field, and his wife reported that he was intermittently confused. Blood cultures grew gram-positive bacilli after 17 hours of incubation; therefore, on October 25, he was called back to the hospital for admission. The blood isolate was subsequently identified as B. anthracis. At admission, his vital signs were as follows: temperature 38.2 [degrees] C, heart rate 108/min, respiratory rate 20/min, blood pressure 121/60 mm Hg, and oxygen saturation 94% on room air. He appeared ill and had decreased breath sounds at the right base. The rest of the examination was unremarkable. Laboratory studies on admission included WBC count 9,500/ [mm.sup.3] with 81% segmented neutrophils, 9% lymphocytes, and 9% monocytes, hematocrit 48.1%, platelet count 196,000/ [mm.sup.3], normal electrolytes and creatinine, SGOT 85 IU/L, SGPT 64 IU/L, alkaline phosphatase 141 IU/L, bilirubin 1.6 mg/dL, and albumin 3.0 mg/dL. On review, the initial chest X-ray showed mediastinal widening (Figure 5), and chest CT on the day of admission showed mediastinal adenopathy with evidence of hemorrhage, normal lung parenchyma Parenchyma
A ground tissue of plants chiefly concerned with the manufacture and storage of food. The primary functions of plants, such as photosynthesis, assimilation, respiration, storage, secretion, and excretion—those associated with living , small bilateral pleural effusions, and a suspected small pericardial effusion (Figure 6). Intravenous penicillin and rifampin were added to the ciprofloxacin. His temperature rose to 39 [degrees] C. Subsquently, vancomycin was added and penicillin was discontinued. On October 26, gastrointestinal bleeding developed, which required blood transfusion, endoscopic injection, and cautery cautery, searing or destruction of living animal tissue by use of heat or caustic chemicals. In the past, cauterization of open wounds, even those following amputation of a limb, was performed with hot irons; this served to close off the bleeding vessels as well as of gastric and duodenal ulcers. On October 27, atrial fibrillation with variable ventricular response developed. On October 28, fever reached a maximum of 39.4 [degrees] C and then decreased to 38.3 [degrees] C. On October 30, WBC peaked at 31,300/[mm.sup.3]. On October 31, enlargement of the right pleural effusion required thoracentesis and removal of 900 cc of serosanguinous fluid (Table 1). The patient was discharged from the hospital on November 9.
[FIGURES 5-6 OMITTED]
On October 14, a 56-year-old African-American woman who worked as a mail sorter in the Hamilton, New Jersey, US Postal Service facility, became ill with vomiting and diarrhea, Followed the next day by subjective fever and chills unrelieved by aspirin. The vomiting and diarrhea improved, but over the next 2 days she had fevers to 38.4 [degrees] C with shaking chills, headache, and fatigue. A nonproductive cough developed, along with mild shortness of breath, and anterior chest pain on inspiration. She had no sore throat or rhinorrhea. On October 19, because of persistent fever and worsening chest pain, she went to a local emergency room. Findings at that time included temperature 38.4[degrees] C, heart rate 120/ min, blood pressure 159/95 mm Hg, and respiratory rate 18/ min. She appeared ill with increased respiratory effort, had decreased breath sounds at both bases, and had a 0.5- to 1.0-cm healing scab on the anterior neck. Initial WBC was normal except for elevation in neutrophil band forms, and hematocrit and platelets were normal. Serum electrolytes, creatinine, and coagulation values were unremarkable, except for hyponatremia. Hepatic enzymes were elevated, and she was hypoxic (Table 1). Her past medical history included a transient ischemic attack. She did not smoke. A chest X-ray showed bibasilar infiltrates and a small right pleural effusion but no mediastinal widening. Initial differential diagnosis included atypical pneumonia versus inhalational anthrax, and the patient was begun on levofloxacin; rifampin was added the next day. Two days later, the fever persisted, dyspnea worsened, and large bilateral pleural effusions developed. Antibiotics were changed to ciprofloxacin, rifampin, and vancomycin. Right-sided thoracenteses were performed on October 21 and 22, and 750 cc and 650 cc of hemorrhagic fluid were removed, respectively. On October 23, a right chest tube was placed. A chest CT on October 22 showed mediastinal and cervical lymphadenopathy, bibasilar infiltrates, and large left pleural effusion. On October 25, the enlarging left-sided effusion effusion /ef·fu·sion/ (e-fu´zhun)
1. escape of a fluid into a part; exudation or transudation.
2. effused material; an exudate or transudate. required chest tube placement. On October 26, the fever resolved, transaminases became normal, and the dyspnea gradually improved. On October 30 and November 1, the chest tubes were removed. On November 5, the patient was discharged from the hospital. Blood for B. anthracis DNA by PCR was positive, as were immunohistochemistry studies for B. anthracis cell-wall and capsule antigens from pleural fluid cytology preparations.
On October 15, a 43-year-old South Asian woman, also a mail sorter at the US Postal Service facility in Hamilton but at different mail sorting machines from those used by the patient in Case 8, became ill. She had intermittent fevers with chills, dry cough with chest discomfort and shortness of breath, myalgias, and fatigue. She also had nausea and vomiting Nausea and Vomiting Definition
Nausea is the sensation of being about to vomit. Vomiting, or emesis, is the expelling of undigested food through the mouth. but no abdominal pain or diarrhea. She complained of "head stuffiness" but no rhinorrhea or sore throat. She also had headache and was reported to be mildly confused. On October 16, when she visited her primary-care physician, she had a temperature of 38 [degrees] C and was started on levofloxacin for bronchitis. Her past medical history was unremarkable, and she did not smoke. On October 18, she went to a local emergency room because of persistent symptoms. Vital signs were as follows: temperature 38.4 [degrees] C, heart rate 120/min, respiratory rate 16/min, and blood pressure 141/85mm Hg, with oxygen saturation 92% on room air and 97% on 4 L of oxygen by nasal cannula. She appeared ill and had decreased breath sounds with egophony at the right base. WBC showed increase in neutrophil band forms; hematocrit and platelet count were normal. She had hyponatremia, but electrolytes, renal function, and coagulation values were otherwise normal. Hepatic enzymes were elevated (Table 1). Blood PCR for B. anthracis DNA obtained 2 days after initiation of antibiotics was negative. A chest X-ray showed right hilar opacity consistent with consolidation or mass, moderate right and minimal left pleural effusions. Antibiotics were changed to azithromycin and ciprofloxacin. Ciprofloxacin was discontinued 24 hours later. On October 19, a chest CT showed increased soft tissue in the mediastinum mediastinum /me·di·as·ti·num/ (me?de-ah-sti´num) pl. mediasti´na [L.]
1. a median septum or partition.
2. (thought to represent adenopathy), right hilar consolidation with possible underlying mass, and large right pleural effusion. Clindamycin and ceftriaxone were added, and thoracentesis was performed with removal of 500 cc of serosanguinous fluid (Table 1). Pleural fluid cytology preparation was positive for B. anthracis cell-wall and capsule antigens by immunohistochemical staining. On October 21, repeat thoracentesis was required, and 800 cc of fluid was removed. On October 22, bronchoscopy found edematous e·dem·a·tous
Marked by edema. , erythematous erythematous
characterized by erythema. mucosa. A transbronchial biopsy showed B. anthracis cell-wall and capsule antigens by immunohistochemical staining. Cultures of endobronchial samples, pleural fluid, and a nasal swab were all negative for B. anthracis, and no other pathogens were identified. On October 23, the fever resolved, other symptoms began to improve, treatment was changed to doxycycline, and the patient was discharged from the hospital on doxycycline on October 26.
On October 25, a 61-year-old Asian woman who worked in the supply room of a New York City New York City: see New York, city.
New York City
City (pop., 2000: 8,008,278), southeastern New York, at the mouth of the Hudson River. The largest city in the U.S. Hospital had onset of malaise and myalgias. Over the next 2 days, she also had fatigue, chills, chest pain, progressively worsening dyspnea, and cough productive of sputum, which was later blood-tinged; she denied fever. On October 28, 2001, when she went to a local hospital (other than her workplace), she was noted to be febrile in the emergency room and normotensive, but her heart rate was 110/rain and respiratory rate 38/min, with room-air oxygen saturation of 92% by pulse oximetry. She was awake, alert, and completely oriented. She had prominent jugular venous distension dis·ten·tion also dis·ten·sion
The act of distending or the state of being distended.
[Middle English distensioun, from Old French, from Latin at 60 degrees. She had a history of hypertension. She did not smoke. Chest examination showed rales heard to the apices a·pi·ces
A plural of apex. bilaterally. Abdominal and cardiovascular examinations were normal except for tachycardia, and she had no peripheral edema. WBC count was slightly elevated; hematocrit and platelets were normal. Serum chemistries and coagulation studies were normal except for hyponatremia, elevated hepatic enzymes, and hypoalbuminemia. The serum lactate dehydrogenase level was 1,370 IU/L. The patient required oxygen delivery by a nonrebreather mask to maintain adequate oxygenation (Table 1). Chest X-ray was initially interpreted as showing pulmonary venous congestion The condition of a network when there is not enough bandwidth to support the current traffic load.
congestion - When the offered load of a data communication path exceeds the capacity. with bilateral pleural effusions. Therapy for congestive heart failure congestive heart failure, inability of the heart to expel sufficient blood to keep pace with the metabolic demands of the body. In the healthy individual the heart can tolerate large increases of workload for a considerable length of time. was initiated, but an echocardiogram ech·o·car·di·o·gram
A visual record produced by echocardiography.
A non-invasive ultrasound test that shows an image of the inside of the heart. in the emergency department showed normal ejection fraction, no substantial wall motion abnormalities, and a small pericardial effusion. Therapy was changed to levofloxacin for atypical pneumonia. The patient's respiratory status worsened, and she was intubated. A CT scan of the chest showed mediastinal lymphadenopathy, massive mediastinal bleeding, thickened bronchial mucosa, and bilateral pleural effusions. Rifampin, gentamicin and subsequently nafcillin nafcillin /naf·cil·lin/ (naf-sil´in) a semisynthetic, acid- and penicillinase-resistant penicillin that is effective against staphylococcal infections; used as the sodium salt. were added to her antimicrobial regimen. Early on October 29, 2001, bilateral chest tubes were placed, and 2.5 liters of serosanguinous fluid was drained from the right side and 1.0 liter from the left (Table 1). On the same day, bronchoscopy showed hemorrhagic mucosa throughout the entire tracheobronchial tracheobronchial /tra·cheo·bron·chi·al/ (-brong´ke-al) pertaining to the trachea and bronchi.
Of or relating to the trachea and the bronchi. tree, friable friable /fri·a·ble/ (fri´ah-b'l) easily pulverized or crumbled.
1. Readily crumbled; brittle.
2. Relating to a dry, brittle growth of bacteria. and collapsible airways, and purulent pu·ru·lent
Containing, discharging, or causing the production of pus.
Consisting of or containing pus
Mentioned in: Lacrimal Duct Obstruction
containing or forming pus. secretions in multiple segments bilaterally. On October 30, the antimicrobial regimen was changed to ciprofloxacin, rifampin, clindamycin, and ceftazidime. Serial echocardiograms documented enlarging pericardial effusion, ultimately with tamponade tamponade /tam·pon·ade/ (tam?po-nad´)
1. surgical use of a tampon.
2. pathologic compression of a part. . The patient's clinical condition progressively worsened, and she died on October 31, after attempted pericardiocentesis. Cultures of blood (after 20 hours) and pleural fluid grew B. anthracis. Autopsy findings included hemorrhagic mediastinitis; immunohistochemical stains confirmed the presence of B. anthracis in multiple organs.
The median age of patients with inhalational anthrax in this series was 56 years (range 43 to 73 years), 70% were male and, except for the patient in Case 10, all were known to or believed to have processed, handled, or received letters containing B. anthracis spores (postal workers [n=6], mail handlers or sorters [n=2], journalist [n=2]). The source of exposure to B. anthracis spores in Case 10, a hospital supply room worker, remains undefined. Four patients had underlying cardiovascular or cerebrovascular disease, one had a remote history of treated sarcoidosis and diet-controlled diabetes mellitus, and one had a history of asthma. None of the patients was a current or recent smoker.
The median incubation period from the time of exposure to onset of symptoms when known (n=6) was 4 days (range 4 to 6 days). Two of the patients (in Cases 8 and 9) are presumed to have been exposed on October 9, when a letter later known to be contaminated with spores of B. anthracis was processed in the postal facility where they worked. The same letter was routed through a second postal facility and processed on October 12, the presumed day of exposure for four additional cases of inhalational anthrax (Cases 3, 4, 5, and 6).
Patients sought care a median of 3.5 days (range 1 to 7 days) after onset of symptoms. Eight of 10 patients were in the initial phase of illness when they first sought care. Of these eight, six received antibiotics with activity against B. anthracis on the same day, and all six survived. Four patients, including one with meningitis, were exhibiting fulminant ful·mi·nant
Occurring suddenly, rapidly, and with great severity or intensity, usually of pain.
ful signs of illness when they first received antibiotics with activity against B. anthracis, and all four died. Table 2 summarizes the symptoms of the 10 patients with bioterrorism-related anthrax. Table 3 lists major initial clinical, laboratory and radiologic findings. The median initial WBC count was 9,800/[mm.sup.3] (range 7,500 to 13,300/[mm.sup.3]). However, the median peak WBC count after presentation and during the course of the illness was 26,400/[mm.sup.3] (range 11,900 to 49,600/[mm.sup.3]). The chest X-ray was abnormal in all patients, but only seven had mediastinal changes.
Pleural effusions were present in all 10 patients and often became large during hospitalization in those who survived. Seven patients required drainage of pleural fluid, three of these with chest tubes; pleural fluid was consistently hemorrhagic with relatively few leukocytes. Pulmonary infiltrates, which were seen in seven patients, involved the right and left lower lobes (one patient), left upper and lower lobes (one), right upper lobe (two), right lower lobe (one), right middle and right lower lobes (one), and bilateral perihilar areas (one). Eight patients had a chest CT performed; mediastinal lymphadenopathy was present in all but one patient.
Blood cultures were obtained before antibiotic therapy was initiated in seven patients, and B. anthracis was isolated in all seven. Blood cultures grew B. anthracis at a median of 18 hours (range 12 to 24 hours). Three patients had the first set of blood cultures obtained after initiation of antibiotic therapy; these cultures revealed no growth. One patient with blood cultures that grew B. anthracis had blood cultures repeated within 24 hours after initiating antibiotics with activity against B. anthracis, and the repeat cultures did not grow.
B. anthracis-specific immunohistochemical tests performed on pleural fluid cytology preparations or transbronchial biopsy specimens were positive in every case in which these tissues were available (three nonfatal cases) (Figure 7A). Three patients had atrial arrythmias (supraventricular tachycardia in Case 2 and atrial fibrillation in Cases 5 and 7), and three patients had pericardial effusion on CT scan. In one patient, pericardial pericardial /peri·car·di·al/ (-kahr´de-al)
1. pertaining to the pericardium.
2. surrounding the heart.
pertaining to the pericardium. tamponade was suspected. Six of 10 patients with inhalational anthrax have survived to date (death rate 40%). Five have been discharged from the hospital, and one is recovering in the hospital. Figure 8 shows the timeline from exposure (when known) to current status for these 10 patients. Autopsy findings in all four patients who died showed hemorrhagic mediastinal lymphadenitis and evidence of disseminated B. anthracis infection (Figure 7B-D B-D Becton, Dickinson & Co. )
[FIGURES 7-8 OMITTED]
Before this outbreak of bioterrorism-related anthrax, only 18 cases of inhalational anthrax had been reported in the United States in the 20th century (1,4,9-21). The most recent case was in 1976 (4). Most cases were related to exposure to animal products, primarily in textile mills processing goat hair, goat skins, or wool (1). Clinical characteristics in the 10 cases due to bioterrorism described here share similarities with previously reported cases but have important differences.
Inhalational anthrax has been described as a biphasic bi·pha·sic
Having two distinct phases: a biphasic waveform; a biphasic response to a stimulus. clinical illness characterized by a 1-to 4-day initial phase of malaise, fatigue, fever, myalgias, and nonproductive cough, followed by a fulminant phase of respiratory distress, cyanosis cyanosis (sī'ənō`sĭs), bluish coloration of the skin, mucous membranes, and nailbeds, resulting from a lack of oxygenated hemoglobin in the blood. , and diaphoresis (1). Death follows the onset of the fulminant phase in 1 to 2 days (2,22). The symptoms of the initial phase of inhalational anthrax in the 10 cases caused by bioterrorism (Table 1) were similar to those of the 18 occupationally related cases previously described (1); however, profound, often drenching sweating, which was a prominent feature in the current cases, was not emphasized in earlier reports. Previous case reports have noted a brief period of improvement between the initial and fulminant phases (1), but this phenomenon was not observed in the current cases. Nausea and vomiting were also frequent symptoms of the initial phase in the current cases, suggesting early involvement of the gastrointestinal tract. Gastrointestinal lesions were observed in 39 of 42 total cases of fatal inhalational anthrax associated with the Sverdlovsk outbreak (23). Most lesions in these fatal cases appeared to represent hematogenous hematogenous /he·ma·tog·e·nous/ (he?mah-toj´e-nus)
1. produced by or derived from the blood.
2. disseminated through the blood stream.
1. spread of B. anthracis to the submucosa submucosa /sub·mu·co·sa/ (sub?mu-ko´sah) areolar tissue situated beneath a mucous membrane.
A layer of loose connective tissue beneath a mucous membrane. of the gastrointestinal tract and did not involve Peyer's patches or, in most cases, mesenteric lymph nodes. The nondistinctive non·dis·tinc·tive
Not phonemically distinctive; not serving to distinguish meaning. nature of the initial phase of inhalational anthrax presents a diagnostic challenge. The chest X-ray appeared to be a sensitive indicator of disease in patients with bioterrorism-associated inhalational anthrax, as none of the 10 patients had an initially normal chest X-ray. Multiple abnormalities were noted on initial chest X-ray, including mediastinal widening, paratracheal fullness, hilar fullness, pleural effusions, and parynchemal infiltrates. Two patients had chest X-rays that were interpreted initially as normal, but abnormalities (mediastinal widening in one case and perihilar mass versus infiltrate in the other) were detected when the X-rays were reviewed by a radiologist. Pulmonary infiltrates or effusion were initially seen in two cases without evidence of mediastinal widening. Chest CT was helpful in further characterizing abnormalities in the lungs and mediastinum and was more sensitive than chest X-ray in revealing mediastinal lymphadenopathy.
The total WBC count was usually normal or only slightly elevated at the time of initial visit to a health-care provider for patients who sought medical care in the initial phase. However, an elevation in the proportion of neutrophils or band forms was frequently noted and was an early diagnostic clue. During the course of illness, WBC counts increased, sometimes markedly, in most patients.
Blood cultures grew B. anthracis even in the initial phase of the illness in all patients who had not received prior antibiotic therapy. Animal models suggest that primates with inhalational anthrax become bacteremic bac·te·re·mi·a
The presence of bacteria in the blood.
bacte·re early in the course of the illness before the fulminant clinical phase develops (24). In contrast, blood cultures rapidly became sterile after initiation of antibiotic therapy, suggesting that prior antibiotic treatment may substantially decrease the sensitivity of blood cultures as a diagnostic test.
The diagnosis of anthrax was established in three patients without growth of B. anthracis from clinical specimens. In all three of these cases, proper cultures were obtained only after initiation of antibiotic therapy. The diagnosis in these patients was established by a history of exposure or occupational and environmental risk with a clinically compatible syndrome, by the identification of B. anthracis in pleural fluid, pleural biopsy, or transbronchial biopsy specimens by immunohistochemical staining with B. anthracis-specific cell wall and capsular cap·su·lar
Of, relating to, or resembling a capsule.
Adj. 1. capsular - resembling a capsule; "the capsular ligament is a sac surrounding the articular cavity of a freely movable joint and attached to the bones" antibodies, or by identifying B. anthracis DNA by PCR on pleural fluid or blood. Serologic data from ELISA available for one patient with inhalational anthrax also demonstrated a >4-fold increase in levels of serum antibody (IgG) to the PA component of anthrax toxins.
The survival of patients with inhalational anthrax in this series (60%) is higher than previously reported (<15%) (1,3). All patients received combination antimicrobial therapy with more than one agent active against B. anthracis. The apparent improvement in survival compared with previous cases suggest that the antibiotic combinations used in these patients may have therapeutic advantage over previous regimens. Limited data on treatment of the survivors suggests that early treatment with a fluoroquinolone fluoroquinolone /flu·o·ro·quin·o·lone/ (-kwin´o-lon) any of a subgroup of fluorine-substituted quinolones, having a broader spectrum of activity than nalidixic acid.
n. and at least one other active drug (7) may improve survival. Other antimicrobial susceptibilities of the isolates associated with this outbreak have been published (7). B. anthracis isolates produce a cephalosporinase (7) that inhibits the antibacterial activity of cephalosporins Cephalosporins Definition
Cephalosporins are medicines that kill bacteria or prevent their growth.
Cephalosporins are used to treat infections in different parts of the body—the ears, nose, throat, lungs, sinuses, and such as ceftriaxone, and cephalosporins should not be used for treatment. Other explanations for the improved survival rate include earlier recognition and initiation of treatment, better supportive care, differences in the pathogenesis of bioterrorism-related anthrax, differences in susceptibility of the hosts, or a combination of the above.
Pleural effusions were a remarkably consistent clinical feature of inhalational anthrax in this series, occurring in all patients. The pleural effusions were often small on presentation, but in the surviving patients effusions were characterized by progressive enlargement and persistence. Drainage of the pleural cavity was required in seven patients. The characteristics of the pleural fluid in all patients were similar: hemorrhagic, with a high protein concentration and relatively few WBCs. Immunohistochemistry demonstrated large quantities of B. anthracis capsule and cell-wall antigens in pleural Pleural
Pleural refers to the pleura or membrane that enfolds the lungs.
Mentioned in: Pneumothorax
emanating from or pertaining to the pleura. tissue or pleural fluid cell blocks.
Case 2 was remarkable in that X-ray findings were dominated by large and progressive pulmonary infiltrates, not by mediastinal widening. In fact, no mediastinal adenopathy was noted on chest CT. Transbronchial biopsies of the patient in Case 2 showed B. anthracis-specific capsular and cell-wall antigens in the lung parenchyma. Previous reports have noted bronchopneumonia bronchopneumonia: see pneumonia. and pulmonary hemorrhagic infarcts in patients with inhalational anthrax. Abramova et al. (23) described focal hemorrhage and necrotizing necrotizing /nec·ro·tiz·ing/ (nek´ro-tiz?ing) causing necrosis.
Causing the death of a specific area of tissue. Human bites frequently cause necrotizing infections. anthrax pneumonia in 11 of 42 patients who died with inhalational anthrax. Characteristics of the spore-containing aerosol or individual host factors may influence pathogenesis, so pulmonary infiltrates may be a more prominent manifestation in some patients with bioterrorism-related inhalational anthrax. Three patients had supraventricular arrythmias, and three had pericardial effusion on chest CT, one of which may have progressed to tamponade. Pericardial effusions may reflect toxin-related local edema or inflammation, hemorrhagic necrosis and infarct infarct /in·farct/ (in´fahrkt) a localized area of ischemic necrosis produced by occlusion of the arterial supply or the venous drainage of the part. extending into the pericardium pericardium: see heart. from the mediastinum, or hematogenous spread of B. anthracis.
Anthrax meningitis is a complication of inhalational anthrax and is characteristically hemorrhagic. Pathologic findings are a hemorrhagic leptomeningitis with edema and inflammatory infiltrates (2,23). Fifty-five percent of patients at Sverdlovsk who died of inhalational anthrax had evidence of meningeal me·nin·ge·al
Of, relating to, or affecting the meninges.
pertaining to the meninges.
meningeal hemorrhage involvement at autopsy. Cerebrospinal fluid was examined in only two patients in our series, and meningitis was documented in one. Three other patients had a history of intermittent confusion, but no meningeal signs were observed, and lumbar punctures were not performed. No predominant underlying diseases or conditions were noted in the patients with bioterrorism-related inhalational anthrax. One patient (Case 5) had a remote history of sarcoidosis but had been free of clinical illness or treatment associated with this diagnosis for the past 25 years. One other case of inhalational anthrax associated with underlying sarcoidosis has been reported (12). The patient in Case 5 also had diabetes mellitus, a condition present in one previously reported case (12). Smoking did not appear to be a risk factor for inhalational anthrax.
In summary, we describe the clinical presentation of the first 10 cases of bioterrorism-related inhalational anthrax in the United States. The clinical presentation in these patients was variable and often resembled a viral respiratory illness, but the interpretation of the initial symptoms in the context of a possible exposure to B. anthracis often led to an early diagnosis. In contrast to previous reports indicating a death rate >85% (1,3), our series suggests that survival may be markedly improved by combination antimicrobial therapy begun during the initial phase of the illness and by aggressive supportive care (e.g., drainage of pleural effusions). Newer methods of detection such as polymerase chain reaction, immunohistochemistry, and sensitive serologic tests are important adjunctive diagnostic modalities that aid in the diagnosis of B. anthracis infections. Further studies are needed to better define optimal antimicrobial regimens, explore the role of adjunctive therapies (e.g., immunoglobulin antitoxin antitoxin, any of a group of antibodies formed in the body as a response to the introduction of poisonous products, or toxins. By introducing small amounts of a specific toxin into the healthy body, it is possible to stimulate the production of antitoxin so that the , corticosteroids, and other toxin inhibitors), and better understand the pathogenesis of inhalational anthrax associated with intentional release.
Table 1. Laboratory findings at initial visit to health-care provider for 10 patients with bioterrorism-related inhalational anthrax, October through November 2001 Case 1 Case 2 Case 3 WBC/mm3 (b) 9,400 9,900 7,500 WBC differential Neutrophils % 76 72 76 Band forms % ND ND 8 Lymphocytes% 15 10 7 Monocytes% 9 17 7 Hematocrit % 45.7 47.1 46.9 Platelet count x 103/ 109 WNL WNL mm3 Sodium mmol/l 132 WNL WNL Potassium mmol/l WNL WNL WNL Chloride mmol/l WNL WNL WNL Bicarbonate mmol/L WNL WNL WNL Creatinine mg/dL WNL 1.2 WNL SGOT IU/L WNL 405 106 SGPT IU/L WNL 408 123 Alkaline WNL 141 165 phosphatase IU/L Albumin g/dL WNL 2.3 2.9 Bilirubin mg/dL 1.5 WNL 1.9 Arterial pH 7.32 7.48 7.45 Arterial PaCO2 mm Hg 37 33 27 Arterial PaO2 mm Hg 208 52 80 (FiO2) (70%) (RA) (RA) Pleural fluid ND 110,000 243,586 RBC/mm3 WBC/mm3 ND 2,260 1,707 (% neutrophils) (58%) (15) Protein g/dL ND 2.6 2.7 LDH IU/L ND 282 1,762 Case 4 Case 5 Case 6 WBC/mm3 (b) 9,700 10,300 13,300 WBC differential Neutrophils % 43 83 78 Band forms % 10 4 ND Lymphocytes% 24 6 11 Monocytes% 15 7 8 Hematocrit % 48.6 43.0 51.4 Platelet count x 103/ WNL WNL WNL mm3 Sodium mmol/l WNL ND WNL Potassium mmol/l WNL ND WNL Chloride mmol/l WNL ND WNL Bicarbonate mmol/L WNL ND WNL Creatinine mg/dL WNL ND WNL SGOT IU/L 153 ND WNL SGPT IU/L 184 ND 44 Alkaline 171 ND WNL phosphatase IU/L Albumin g/dL 2.9 ND WNL Bilirubin mg/dL 1.7 ND WNL Arterial pH 7.46 ND ND Arterial PaCO2 mm Hg 38 ND ND Arterial PaO2 mm Hg 66 ND ND (FiO2) (RA) Pleural fluid 179,841 ND ND RBC/mm3 WBC/mm3 1,633 ND ND (% neutrophils) (6) Protein g/dL 4.3 ND ND LDH IU/L 965 ND ND Case 7 Case 8 Case 9 (a) WBC/mm3 (b) 9,700 8,100 11,200 WBC differential Neutrophils % 79 50 67 Band forms % ND 6 14 Lymphocytes% 14 30 8 Monocytes% 7 10 11 Hematocrit % 44.7 45.3 42.5 Platelet count x 103/ WNL WNL WNL mm3 Sodium mmol/l 134 133 133 Potassium mmol/l 3.4 WNL WNL Chloride mmol/l WNL 98 WNL Bicarbonate mmol/L 20 WNL WNL Creatinine mg/dL WNL WNL WNL SGOT IU/L ND 269 130 SGPT IU/L ND 168 120 Alkaline ND WNL 147 phosphatase IU/L Albumin g/dL ND WNL 3.4 Bilirubin mg/dL ND WNL WNL Arterial pH ND 7.51 ND Arterial PaCO2 mm Hg ND 26 ND Arterial PaO2 mm Hg ND 58 ND (FiO2) (RA) Pleural fluid ND 80,000 "Many" RBC/mm3 WBC/mm3 ND 785 (12) 286 (71) (% neutrophils) Protein g/dL 2.01 4.8 4.1 LDH IU/L 261 319 740 Case 10 WBC/mm3 (b) 11,400 WBC differential Neutrophils % 83 Band forms % ND Lymphocytes% 9 Monocytes% 7 Hematocrit % 46.3 Platelet count x 103/ WNL mm3 Sodium mmol/l 134 Potassium mmol/l WNL Chloride mmol/l WNL Bicarbonate mmol/L WNL Creatinine mg/dL WNL SGOT IU/L 240 SGPT IU/L 263 Alkaline WNL phosphatase IU/L Albumin g/dL 3.3 Bilirubin mg/dL WNL Arterial pH 7.41 Arterial PaCO2 mm Hg 40 Arterial PaO2 mm Hg 122 (FiO2) (100% NRBR) Pleural fluid 73,000 RBC/mm3 WBC/mm3 3,000 (% neutrophils) (90) Protein g/dL 4.2 LDH IU/L 1,264 (a) The patient in Case 9 was initially seen as an outpatient 2 days before hospital admission, but had no laboratory studies performed at that time. These results were obtained from studies done on the day of admission. (b) WBC = white blood cells; WNL = within normal limits; ND = not done; NA = not available; SGOT = serum glutamic oxalacetic transaminase; SGPT = serum glutamic pyruvic transaminase; Fi[O.sub.2] = fraction of inspired [O.sub.2]; RA = room air; NRBR = nonrebreather mask; RBC = red blood cells; LDH = lactate dehydrogenase Table 2. Symptoms for 10 patients with bioterrorism-related inhalational anthrax, October-November 2001 Symptoms n=10 Fever, chills 10 Fatigue, malaise, lethargy 10 Cough (minimally or nonproductive) 9 Nausea or vomiting 9 Dyspnea 8 Sweats, often drenching 7 Chest discomfort or pleuritic pain 7 Myalgias 6 Headache 5 Confusion 4 Abdominal pain 3 Sore throat 2 Rhinorrhea 1 Table 3. Initial clinical findings in 10 patients with bioterrorism- related inhalational anthrax, October - November 2001 Physical findings Fever (>37.8 [degrees] C) 7/10 Tachycardia (heart rate >100/min) 8/10 Hypotension (systolic blood pressure <110 1/10 mm Hg) Laboratory results White blood cell count (median, range) 9.8 x [10.sup.3]/ [mm.sup.3] Differential -- neutrophilia (>70%) 7/10 Neutrophil band forms (>5%) 4/5 Elevated transaminases (a) 9/10 (SGOT or SGPT > 40) Hypoxemia 6/10 (Alveolar-arterial oxygen gradient >30mm Hg on room air [O.sub.2] saturation <94%) Metabolic acidosis 2/10 Elevated creatinine (>1.5 mg/dL) 1/10 Chest X-ray findings Any abnormality 10/10 Mediastinal widening 7/10 Infiltrates/consolidation 7/10 Pleural effusion 8/10 Chest computed tomography findings Any abnormality 8/8 Mediastinal lymphadenopathy, widening 7/8 Pleural effusion 8/8 Infiltrates, consolidation 6/8 (a) SGOT = serum glutamic oxalacetic transaminase; SGPT = serum glutamic pyruvic transaminase
We thank Sherrie Bruce, Rebecca Dixon, Anexis Lopez, Pat McConnon, Carmen Resurreccion, Kay Vydareny, the laboratories of the National Center for Infectious Diseases, the laboratories of affected states, the U.S. Department of Defense, and Epidemic Intelligence Service The Epidemic Intelligence Service is a program of the United States' Centers for Disease Control and Prevention. Established in 1951 due to biological warfare concerns arising from the Korean War, it has become a hands-on two-year postgraduate training program in epidemiology, with Officers for their assistance in preparing this article.
Dr. Jernigan is a medical epidemiologist with the National Center for Infectious Diseases, Centers for Disease Control and Prevention, and assistant professor of medicine with Emory University School of Medicine. He has been extensively involved in the clinical evaluation of the anthrax cases associated with this outbreak.
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John A. Jernigan, * David S. Stephens, * ([dagger]) David A. Ashford, * Carlos Omenaca, ([double dagger]) Martin S. Topiel, ([section]) Mark Galbraith, ([paragraph]) Michael Tapper, (#) Tamara L. Fisk Fisk , James 1834-1872.
American railroad financier and speculator who attempted in 1869 to corner the gold market with Jay Gould, leading to Black Friday, a day of nationwide financial panic. , * ([dagger]) Sherif she·rif also sha·rif
1. A descendant of the prophet Muhammad through his daughter Fatima.
2. The chief magistrate of Mecca in Ottoman times.
3. A Moroccan prince or ruler. Zaki, * Tanja Popovic, * Richard F. Meyer, * Conrad P. Quinn, * Scott A. Harper, * Scott K. Fridkin, * James J. Sejvar, * Colin W. Shepard, * Michelle McConnell, * Jeannette Guarner, * Wun- Ju Shieh, * Jean M. Malecki, ** Julie L. Gerberding, * James M. Hughes, * Bradley A. Perkins, * and members of the Anthrax Bioterrorism Investigation Team (1)
(*) Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ([dagger]) Emory University School of Medicine, Atlanta, Georgia, USA; ([double dagger]) Cedars Medical Center, Miami, Florida, USA; ([section]) Virtua Health, Mount Holly, New Jersey, USA; ([paragraph]) Winchester Medical Center, Winchester, Virginia, USA; (#) Lenox Hill Hospital Lenox Hill Hospital, on Manhattan's Upper East Side, is a 652-bed, acute care hospital and a major teaching affiliate of NYU Medical Center. Founded in 1857 as the German Dispensary, today's 10-building Lenox Hill Hospital complex has occupied its present site since 1868 when it , New York City, New York, USA; and (**) Palm Beach County Department of Public Health, West Palm Beach, Florida West Palm Beach, also known as West Palm, is the most populous city in Palm Beach County, Florida, USA. The city is also the oldest incorporated municipality in South Florida. According to the University of Florida's 2006 estimates, the city had a population of 107,617. , USA
(1) Members of the team who contributed to the work presented in this manuscript are J. Aguilar, M. Andre, K. Baggett, B. Bell, D. Bell, M. Bowen, G. Carlone, M. Cetron, S. Chamany, B. De, C. Elie, M. Fischer, A. Hoffmaster, K. Glynn, R. Gorwitz, C. Greene, R. Hajjeh, T. Hilger, J. Kelly, R. Khabbaz, A. Khan, P. Kozarsky, M. Kuehnert, J. Lingappa, C. Marston, J. Nicholson, S. Ostroff, T. Parker, L. Petersen, R. Pinner, N. Rosenstein, A. Schuchat, V. Semenova, S. Steiner, F. Tenover, B. Tierney, T. Uyeki, S. Vong, D. Warnock, C. Spak, D. Jernigan, C. Friedman, M. Ripple, D. Patel, S. Pillai, S. Wiersma, R. Labinson, L. Kamal, E. Bresnitz, M. Layton, G. DiFerdinando, S. Kumar, P. Lurie, K. Nalluswami, L. Hathcock, L. Siegel, S. Adams, I. Walks, J. Davies-Coles, M. Richardson, K. Berry, E. Peterson, R. Stroube, H. Hochman, M. Pomeranz, A. Friedman-Kien, D. Frank, S. Bersoff-Matcha, J. Rosenthal, N. Fatteh, A. Gurtman, R. Brechner, C. Chiriboga, J. Eisold, G. Martin, K. Cahill, R. Fried, M. Grossman, and W. Borkowsky.
Address for correspondence: John A. Jernigan, NCID, CDC, Mail-stop E68, 1600 Clifton Road, N.E., Atlanta, GA 30333 USA; fax: 404-498-1244; e-mail: email@example.com