1. Bioterrorism Agents – Plague Lesson 3 Differential Diagnosis

2. Objectives List the diseases that should be considered in the differential diagnosis of plagueList the diseases that should be considered in the differential diagnosis of plague Describe how to rule out other diseases when diagnosing plagueDescribe how to rule out other diseases when diagnosing plague

3. Bubonic Plague Incubation: 2 to 6 daysIncubation: 2 to 6 days SymptomsSymptoms –Chills, high fever –Swollen and painful lymph nodes in groin, thigh, underarm and/or neck –Buboes at site of inoculation –Lymph nodes not hot, skin smooth and red –Rapid pulse –Hypotension

4. Bubonic Plague Disease ProgressionDisease Progression –Septicemia –Pneumonic Plague –Meningitis (rare) Other SymptomsOther Symptoms –Restlessness, confusion, lack of coordination –Intestinal discomfort –Lymph nodes may suppurate second week

5. Bubonic Plague Differential Diagnosis Capnocytophaga canimorsusCapnocytophaga canimorsus CellulitisCellulitis Lymphogranuloma venereumLymphogranuloma venereum Non-specific infectionsNon-specific infections Lymphogranuloma venereum

6. Bubonic Plague Differential Diagnosis Streptococcal or staphylococcal adenitis (Staphylococcal aureus, Staphylococcal pyogenes) Purulent/ inflamed lesion often distal to nodes Purulent/ inflamed lesion often distal to nodes Involved nodes more likely to be fluctuant Involved nodes more likely to be fluctuant Ascending lymphangitis or cellulitis may be present Ascending lymphangitis or cellulitis may be present Tularemia (Francisella tularensis) Ulcer or pustule distal to nodes Ulcer or pustule distal to nodes Rarely as fulminant as in plague Rarely as fulminant as in plague Systemic toxicity uncommon Systemic toxicity uncommon Cat scratch disease (B. henselae) History of cat contact/scratch History of cat contact/scratch Indolent clinical course Indolent clinical course Primary lesion at site of scratch Primary lesion at site of scratch No systemic toxicity No systemic toxicity © 2003 CIDRAP/IDSA

7. Bubonic Plague Differential Diagnosis Mycobacterial infection, including scrofula (Mycobacterium tuberculosis and other Mycobacterium species) Adenitis occurs in cervical region Adenitis occurs in cervical region Usually painless Usually painless Indolent clinical course Indolent clinical course More likely to occur in immunocompromised patients More likely to occur in immunocompromised patients Lymphogranuloma venereum (Chlamydia trachomatis) Adenitis occurs in the inguinal region Adenitis occurs in the inguinal region Sexual exposure 10-30 days previously Sexual exposure 10-30 days previously Suppuration, fistula tracts common Suppuration, fistula tracts common Exquisite tenderness usually absent Exquisite tenderness usually absent Although patients may appear ill (headache, fever, myalgias), systemic toxicity not present Although patients may appear ill (headache, fever, myalgias), systemic toxicity not present © 2003 CIDRAP/IDSA

8. Bubonic Plague Differential Diagnosis Chancroid (Hemophilus ducreyi) Adenitis occurs in inguinal region Adenitis occurs in inguinal region Ulcerative lesion present Ulcerative lesion present Systemic symptoms uncommon; toxicity does not occur Systemic symptoms uncommon; toxicity does not occur Primary genital herpes Genital area Genital area Adenitis occurs in the inguinal region Adenitis occurs in the inguinal region Severe systemic toxicity not present Severe systemic toxicity not present Primary or secondary syphilis (Treponema pallidum) Enlarged lymph nodes in inguinal region Enlarged lymph nodes in inguinal region Lymph nodes generally painless Lymph nodes generally painless Chancre may be noted Chancre may be noted Strangulated inguinal hernias Evidence of bowel involvement Evidence of bowel involvement © 2003 CIDRAP/IDSA

9. Pneumonic Plague Incubation: 2 to 4 days (Range: 1-6 days)Incubation: 2 to 4 days (Range: 1-6 days) SymptomsSymptoms –Fever, chills, malaise, myalgias –Productive cough, watery mucoid –Chest pain, dyspnea –Hemoptysis –Gastrointestinal –Cervical Bubo (rare)

10. Pneumonic Plague Rapidly progressiveRapidly progressive Respiratory failure within 2 to 4 daysRespiratory failure within 2 to 4 days Chest X-Rays – bilateral patchy infiltratesChest X-Rays – bilateral patchy infiltrates Shock, hypotension, multi-organ failureShock, hypotension, multi-organ failure Treat within 24 hours or almost universally fatalTreat within 24 hours or almost universally fatal

11. Pneumonic Plague

12. Primary Pneumonic Plague Outbreak Diagnoses Presumptive; especially if associatedPresumptive; especially if associated Rule out other causesRule out other causes –Severe pneumonia –Rapidly progressive respiratory infection –With or without sepsis

13. Primary Pneumonic Plague Differential Diagnosis Inhalational anthraxInhalational anthrax TularemiaTularemia Community-acquired bacterial pneumoniaCommunity-acquired bacterial pneumonia Viral pneumoniaViral pneumonia Q feverQ fever Anthrax

14. Primary Pneumonic Plague Differential Diagnosis Inhalational anthrax (Bacillus anthracis) Widened mediastinum and pleural effusions Widened mediastinum and pleural effusions Not true pneumonia Not true pneumonia Minimal sputum production Minimal sputum production Hemoptysis uncommon Hemoptysis uncommon Tularemia (Francisella tularensis) Not as rapid or fulminant as in pneumonic plague © 2003 CIDRAP/IDSA

15. Primary Pneumonic Plague Differential Diagnosis Community-acquired bacterial pneumonia Mycoplasmal pneumonia (Mycoplasma pneumoniae) Mycoplasmal pneumonia (Mycoplasma pneumoniae) Pneumonia caused by Chlamydia pneumoniae Pneumonia caused by Chlamydia pneumoniae Legionnaires' disease (Legionella pneumophila or other Legionella species) Legionnaires' disease (Legionella pneumophila or other Legionella species) Psittacosis (Chlamydia psittaci) Psittacosis (Chlamydia psittaci) Other bacterial agents (e.g., Staphyloccocus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis) Other bacterial agents (e.g., Staphyloccocus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis) Rarely as fulminant Rarely as fulminant Usually occur in persons with underlying pulmonary or other disease or in the elderly Usually occur in persons with underlying pulmonary or other disease or in the elderly Bird exposure with psittacosis Bird exposure with psittacosis Gram stain may be useful Gram stain may be useful Community outbreaks not as explosive as pneumonic plague outbreak Community outbreaks not as explosive as pneumonic plague outbreak S. pneumoniae usually institutional S. pneumoniae usually institutional Community outbreaks of Legionnaires' disease often involve exposure to cooling systems Community outbreaks of Legionnaires' disease often involve exposure to cooling systems © 2003 CIDRAP/IDSA

16. Primary Pneumonic Plague Differential Diagnosis Viral pneumonia Influenza Influenza Hantavirus Hantavirus RSV RSV CMV CMV Influenza generally seasonal Influenza generally seasonal History of recent cruise ship travel or travel to tropics History of recent cruise ship travel or travel to tropics Exposure to excrement of mice with Hantavirus Exposure to excrement of mice with Hantavirus RSV usually occurs in children RSV usually occurs in children CMV usually occurs in immunocompromised patients CMV usually occurs in immunocompromised patients Q fever (Coxiella burnetii) Exposure to infected parturient cats, cattle, sheep, goats Exposure to infected parturient cats, cattle, sheep, goats Severe pneumonia not prominent Severe pneumonia not prominent © 2003 CIDRAP/IDSA

17. Septicemic Plague Incubation: Most common as complicationIncubation: Most common as complication SymptomsSymptoms –Fever, chills, prostration –Gastrointestinal Disease ProgressionDisease Progression –Pupura –DIC –Amputation Pupura

18. Septicemic Plague Differential Diagnosis Meningococcemia Evidence of meningitis Septicemia caused by other gram- negative bacteria Underlying illness usually present © 2003 CIDRAP/IDSA

19. Review Questions Plague Lesson 3

20. Plague Review Question Lesson 3, Question 1 36yo, F, Chicago, IL36yo, F, Chicago, IL HousekeeperHousekeeper No hx of travel, animal exposureNo hx of travel, animal exposure SymptomsSymptoms –Severe abdominal pain –Productive cough –Shortness of breath

21. Plague Review Question Lesson 3, Question 1 Exam FindingsExam Findings –Productive cough, thick, bloody sputum –Bilateral rales –Little-to-no air movement lower left lung field –Chest X-Ray – bilateral infiltrates –CSF – Cloudy –Temperature – 102.3  F –Pulse rapid and thready –Liver not enlarged, no enlarged lymph nodes What diagnoses would you rule out?

22. Plague Review Question Lesson 3, Question 1 What diagnoses would you rule out? A.Anthrax B.Tularemia C.Pneumonic Plague D.Bubonic Plague

23. Plague Review Question Lesson 3, Question 1 What diagnoses would you rule out? C. Pneumonic Plague

24. Plague Review Question Lesson 3, Question 2 32yo, M, Philadelphia, PA32yo, M, Philadelphia, PA Computer ProgrammerComputer Programmer No hx travel, Healthy dogNo hx travel, Healthy dog SymptomsSymptoms –Headache, chills, fever x 2 days –Vomiting x 1 day –Orange-sized swelling, left inguinal –Delirious What illnesses would you include in differential?

25. Plague Review Question Lesson 3, Question 2 What illnesses would you include in differential? A.Tularemia B.Chancroid C.Cat-Scratch Fever D.Bubonic Plague

26. Plague Review Question Lesson 3, Question 2 What illnesses would you include in differential? D. Bubonic Plague

27. Plague Review Question Lesson 3, Question 3 56yo, M, Miami, Florida56yo, M, Miami, Florida SalesmanSalesman Hx of Travel to New Mexico last weekHx of Travel to New Mexico last week No hx of animal exposureNo hx of animal exposure SymptomsSymptoms –Malaise, myalgia, chills, headache, GI sxs x 3 days –Worsening sx’s, severe abdominal, productive cough, shortness of breath x 1 day –Today – Pupura, DIC, hypotension How would you relate it to plague?

28. Plague Review Question Lesson 3, Question 3 How would you relate it to plague? A.Presence of gram-positive bacteria B.Hx of travel to plague endemic area C.Rapid progression of disease D.B and C

29. Plague Review Question Lesson 3, Question 3 How would you relate it to plague? D.Both B and C Hx of travel to plague endemic area Rapid progression of disease