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°C, and heart rate 109/min; blood pressure and respiratory rate were normal. Initial pulmonary, heart, and abdominal examinations were reported as normal. No nuchal rigidity was observed. He was not oriented to person, place, or time. Admission laboratory values included a normal total white blood cell (WBC) count, but the platelet count was low. Serum chemistries were normal, except for borderline hyponatremia and elevated total bilirubin. 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) analysis showed WBC count 4,750/µL (81% neutrophils), red blood cell count 1,375/µL, 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, metronidazole, doxycycline, ampicillin, 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 mediastinal lymphadenitis, and immunohistochemical staining showed disseminated B. anthracis in multiple organs.
Initial chest X-ray (Case 1) showing prominent superior mediastinum and possible small left pleural effusion.
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 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 in August 2001. He did not smoke. He was admitted to the hospital on October 1. Temperature was 38.5°C, heart rate 109/min, respiratory rate 20/min, and blood pressure 108/61 mm Hg. He had bilateral conjunctival injection and bilateral pulmonary rhonchi. 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 values showed hypoxia ( 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).
Chest X-ray (Case 2) showing diffuse consolidation consistent with pneumonia throughout the left lung. There is no evidence of mediastinal widening.
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 by PCR. Bronchoscopy showed bloody secretions in the right lower lobe and left lung, with severe mucosal hyperemia, mottling, 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 spp., acid-fast bacteria, Pneumocystis carinii, Chlamydia spp., Leptospira, and Hantavirus and other viral pathogens were negative. The hospital course included an episode of supraventricular tachycardia with hypotension, maximum WBC count 26,800/ mm3, 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 immunohistochemical staining. 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 (ELISA). The patient's condition gradually improved, and he was discharged from the hospital October 23 on oral ciprofloxacin.
Chest X-ray (Case 2) showing diffuse consolidation consistent with pneumonia throughout the left lung. There is no evidence of mediastinal widening.
Computed tomography of chest (Case 2) showing bilateral pulmonary consolidation and pleural effusions.
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, night sweats, nausea, and vomiting. On October 19, when he arrived at a local hospital, he was afebrile and normotensive. 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 ( Table 1 ). A chest X-ray showed a widened mediastinum (especially in the right paratracheal region), bilateral hilar masses, bilateral pleural effusions, and a small right lower lobe air space opacity. CT of the chest showed diffuse mediastinal edema; 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, 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 developed, and several shallow gastric ulcers were noted on upper endoscopy. On October 28, the patient had signs of hemolytic anemia and thrombocytopenia, which was treated with plasmapheresis. Hematologic 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 sweats, intermittent blurred vision, and photophobia. A mild dry cough, dyspnea on exertion, and pleuritic 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/µL (all lymphocytes), 20 RBC/µL, with normal glucose and protein. No organisms were seen on Gram stain of the CSF, and CSF culture did not grow. An anteroposterior 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. 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, 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°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. 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°C, pulse 93 to 150/min 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 and tachycardia. WBC count was 18,800/mm3 with a differential of 73% segmented neutrophils, 6% bands, 11% lymphocytes, and 8% monocytes. Hematocrit was 55%, and platelets were 141,000/mm3. 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) was 76 IU/lL and alanine aminotransferase (ALT) was 77 IU/L. Coagulation studies were normal. Arterial pH was 7.42, PaCO2 25 mm Hg, PaO2 66 mm Hg, and O2 saturation 93% on 2 L of O2/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 showed atrial fibrillation. The patient was intubated, ventilated, 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 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 (SGPT) 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. 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°C, blood pressure 76/48 mm Hg, heart rate 152/min, 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 abdomen with absent bowel sounds. WBC count was 31,200/mm3 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 (SGOT) was 47 IU/L, SGPT 33 IU/L, and alkaline phosphatase 197 IU/L. Prothrombin time was 13.3 seconds and partial thromboplastin time was 40 seconds. Penicillin, ceftriaxone, rifampin, and levofloxacin were begun. Respiratory distress developed, which required endotracheal intubation and mechanical ventilation. Soon thereafter signs consistent with peritonitis were observed. Arterial pH was 7.13, PaCO2 37 mm Hg, PaO2 106 mm Hg, and oxygen saturation 95% after intubation on 100% FiO2. 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, air in the portal venous system, mesenteric edema, diffuse small bowel edema, and small collections of intramural air involving several parts of the jejunum. 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 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°C, and 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 ( 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°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/mm3 with 81% segmented neutrophils, 9% lymphocytes, and 9% monocytes, hematocrit 48.1%, platelet count 196,000/ mm3, 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, 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°C. Subsquently, vancomycin was added and penicillin was discontinued. On October 26, gastrointestinal bleeding developed, which required blood transfusion, endoscopic injection, and cautery 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°C and then decreased to 38.3°C. On October 30, WBC peaked at 31,300/mm3. 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.
Computed tomography of chest (Case 7) showing mediastinal adenopathy and small bilateral pleural effusions.
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°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°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 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 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°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°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 (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, erythematous 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 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/min 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 at 60 degrees. She had a history of hypertension. She did not smoke. Chest examination showed rales heard to the apices 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 with bilateral pleural effusions. Therapy for congestive heart failure was initiated, but an echocardiogram 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 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 tree, friable and collapsible airways, and purulent 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. 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.
Emerging Infectious Diseases. 2001;7(6) © 2001 Centers for Disease Control and Prevention (CDC)
Cite this: Bioterrorism-Related Inhalation Anthrax: The First 10 Cases Reported in the United States - Medscape - Nov 01, 2001.