The concept of disease, controlled by the International Health Regulations Smallpox Plague Disease, Prevention, and Intervention

Progression of Smallpox Incubation Period Prodrome Stage MaculesPapulesVesiclesPustulesScabsScars

Smallpox Prodrome Incubation period 12 days (range 7-17 d) Prodrome –abrupt onset of fever >101 o F –malaise, headache, muscle pain, nausea, vomiting, backache –lasts 1- 4 days

Smallpox Rash Enanthem (mucous membrane lesions) appears ~ 24 hours before skin rash –Minute red spots on the tongue and oral/pharyngeal mucosa –Lesions enlarge and ulcerate quickly –Become infectious from lesions in mouth –Virus titers in saliva highest and most infectious during first week of exanthem (skin rash)

Exantham (skin rash) – (21 days) Exantham (skin rash) – (21 days) Stages: macules, papules, vesicles, pustules, scabs Pustules raised, round, firm - like small beads in the skin (“shotty”) Umbilication common Begins and most dense on face and extremities (centrifugal distribution) Begins and most dense on face and extremities (centrifugal distribution) Lesions on palms and soles (>50% of cases) Lesions on palms and soles (>50% of cases) Lesions in same stage and evolve slowly (1-2 days/stage) Lesions in same stage and evolve slowly (1-2 days/stage) Smallpox Rash

Ordinary Smallpox

Pustular lesions on palms Flattened lesions on soles

Smallpox Ordinary Type (Discreet lesions)

Smallpox Ordinary Type (Dense lesions)

Smallpox Flat-type

Smallpox Hemorrhagic Type

Varicella

SMALLPOX Deep, hard lesions Round, well circumscribed Confluent or umbilicated Lesions at same stage of development CHICKEN POX Superficial Not well circumscribed Confluence and umbilication uncommon Lesions at all stages of development Differential Diagnosis

SMALLPOX CHICKENPOX

Smallpox Chickenpox Chickenpox

Smallpox Varicella

Smallpox Outbreak Control Activities and Strategies

Surveillance and Containment (Ring Vaccination) Case(s) Contacts of Case(s) Contacts of Contacts Search for cases Search for cases Provide a ring of immunity around each case Provide a ring of immunity around each case -Vaccinate close contacts -Vaccinate close contacts of contacts Required to control disease Required to control disease - most efficient use of vaccine - minimize adverse reactions

Surveillance Pre-Event Surveillance –Identify cases with typical presentation –Rapid laboratory confirmation –Confirmation initiates contact vaccination –Passive with more specificity Post-Event Surveillance –Identify all potential cases (typical/atypical) –Clinical diagnosis can initiate contact vaccination –Active with increased sensitivity

Epidemiologic Investigation Identify source of initial introduction(s) Identify contacts and other population(s) at risk Characterize and define outbreak –Identify unusual/unexpected features –Scope Monitor effectiveness of control measures Communicate information and define public health recommendations

Contact Tracing Goal is to find as many contacts as possible –Contact with patient after onset of fever –Prioritize based on closeness, length, and date of exposure –If too many to find quickly, consider all people in same room (or possibly facility) with smallpox case after onset of fever as contacts

Examples: –Highest priority - people who live full-time in home and other face-to-face contacts after onset of fever –Next priority – non face-to-face contacts exposed in a medical care facility or in home –Last priority – people in same facility after onset of fever (other than home or hospital) but without face-to-face contact Contact Tracing

Isolation and Quarantine

Goals of Smallpox Isolation Protect others from becoming infected –Healthcare personnel –Response personnel –Other patients Isolate smallpox patient –Prevent sharing of airspace (respiratory isolation) –Prevent direct contact (protective clothing) –Prevent contact with infectious materials (decontamination)

Prevent sharing of airspace with potentially infectious patients Negative pressure isolation rooms. Separate facilities for larger groups. Respirators for unvaccinated care- providers.

Personal Protective Equipment Use disposable gloves, gowns, and shoe covers. Reusable bedding and clothing should be autoclaved or laundered in hot water with bleach.

Respiratory Protection - Smallpox Airborne precautions Recommendation: fitted NIOSH N95 or greater respirators for personnel entering patient room Properly Fitted – air goes through mask filter

Isolation Strategies 3 groups to consider –Confirmed or suspected smallpox cases –Febrile vaccinated contacts –Asymptomatic (vaccinated) contacts under surveillance

Confirmed/Suspected Smallpox Cases (Few) Known or presumed infectious individuals Hospital isolation room(s) Rooms under negative pressure At least 6 to12 air changes/hour Air vented to outside Air not re-circulated to other rooms or areas

Confirmed/Suspected Smallpox Cases (Many) Designated Facility for smallpox patients Aerosol precautions not needed if only potential smallpox cases in facility and no shared ventilation system –All people admitted/entering facility vaccinated

Febrile Vaccinated Contacts Vaccinated contacts with fever (no rash) –Two successive temps > 101º F (38ºC) –Less need for medical care –No shared ventilation system –Can be housed in same facility with smallpox cases or separate facility –All persons in facility require vaccination

Asymptomatic Vaccinated Contacts Not infectious –Own home or other lodging –No special ventilation or medical requirements All other persons staying in home must also be vaccinated –Household members with contraindications stay elsewhere Fever surveillance for 18 days from last exposure or 14 days from vaccination

Decontamination Air: –UV Light Sensitive –Exhaust, Good Air Flow Surfaces: –Diluted bleach solution (Fresh every day) –Hospital disinfectants Blood, pus contaminated equipment: –Wash before disinfecting

Decontamination Laundry: –Contain separately –Dissolving laundry bags if available –Don’t sort first, wash, then sort –Hot water with detergent and/or bleach Household: –Basic cleaning –Wash all clothing in hot w/ bleach if possible –Public health review of home

Plague

Objectives Identify plague bacterium Epidemiology Natural Occurrence

Bio-Terror Threat Plague can cause large numbers of cases Could create panic Considered for use since 14 th century

Clinical Syndromes BubonicPneumonicSepticemic Plague Meningitis Pharyngeal “Safety Pin” Y. Pestis in blood

Bubonic Plague Infected flea bite Exposure through break in skin No person-to-person Untreated progresses to pneumonic

Pneumonic Plague Inhalation of plague bacteria Disease progression –Respiratory failure –Shock –Rapid death Person-to-person transmission

Septicemic Plague Primary Form –Direct inoculation in bloodstream Secondary Form –Development of untreated pneumonic or bubonic plague

Epidemiology Natural Reservoirs Bites of infected flea Blood meal from bacteremic animal Regurgitates into human/ animal host Common reservoirs –Deer mice –Ground squirrels

Epidemiology Transmission Bite of infected flea Respiratory droplets Direct contact (1,5-2 m) Direct skin/mucous membrane less common BT event – Respiratory droplets or aerosols

Plague Incidence Worldwide, All inhabited continents, but Australia 1,500 to 3,000 cases annually Greatest Concentrations –Asia, South America

Plague Bioterrorism Scenario Most dangerous as aerosol Outbreak of pneumonic Possibly pharyngeal or ocular Report all suspect cases to public health immediately

Bubonic Plague Incubation: 2 to 6 days Symptoms –Lymphadenopathy, fever –Buboes at site of inoculation Disease Progression - Untreated –Septicemia –Secondary Pneumonic Plague –Meningitis (rare)

Bubonic Plague

Pneumonic Plague Incubation: 2 to 4 days (range 1 to 6 days) Symptoms –Acute fever, chills, malaise, myalgias –Productive cough –Watery mucoid sputum, may be bloody –Associated chest pain, increasing dyspnea

Pneumonic Plague Disease Progression –Adult Respiratory Distress Syndrome –Refractory pulmonary edema –Signs of shock –Without treatment in less than 24 hours, almost universally fatal

Pneumonic Plague Coughing patient can spread Respiratory precautions Rapidly expanding infiltrates Pulmonary parenchymal necrosis and hemorrhage Occasional pulmonary abscesses Enlarged hilar nodes and pleural effusions

Pneumonic Plague

Septicemic Plague Incubation: Most common as complication of pneumonic or bubonic plague Symptoms –Acute fever, chills, prostration, abdominal pain, nausea, vomiting Disease Progression –Purpura –DIC –Hypotension and other signs of shock –Fatal if not treated

Infection Control Large numbers of plague bacilli Respiratory droplet spread in close direct contact Respiratory droplet precautions with suspect cases Contact public health

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

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

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

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

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

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

Laboratory confirmation Critical for first cases Collect immediately and before antibiotics Store appropriately Presumptive diagnoses

Specimens Respiratory Pharyngeal swabs Tracheal washes or aspirates Sputum specimens Trans-thoracic lung aspirates Pleural fluid collection Testing – Staining, culture, DNA amplification

Specimens Tissues Lung tissue Lymph node tissue SpleenLiver Testing – Culture, Gram stain

Specimens Tissues (Autopsy) LungLiverSpleen Lymph nodes Skin lesions Kidney Testing – PCR (Specimens kept fresh frozen, unpreserved)

Specimens Blood Baseline before antibiotics Convalescent –Minimum 14 days apart –3 to 4 weeks after symptom onset Two or more sequentially collected samples preferred

Laboratory Testing Pneumonic Plague Collect before initiating therapy Sputum, blood, lymph node aspirate Gram Stain and culture –Gram-negative coccobacillus –Bipolar (safety pin) staining Acute and convalescent bloods for public health

Recommended Plague Treatment Contained Casualty - Adults Preferred Streptomycin 1g IM BID Gentamicin 5 mg/kg IM or IV daily OR 2 mg/kg loading with 1.7 mg/kg IM or IV TID Alternative Doxycycline 100mg IV BID or 200mg IV Ciprofloxacin 400mg IV BID Chloramphenicol 25 mg/kg IV QID

Recommended Plague Treatment Mass Casualty - Adults Preferred Doxycycline 100 mg PO BID Ciprofloxacin 500 mg PO BID Alternative Chloramphenicol 25 mg/kg PO QID

Plague Infection Control Precautions Isolation for 48 hours of antibiotic treatment or until clinical improvement BubonicStandard PneumonicStandard and Respiratory SepticemicStandard SuspectRespiratory and Isolation

Plague Infection Control Cohort and Droplet precautions if no isolation available Isolation of contacts may increase in importance for outbreak control Corpses – Standard Precautions

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