Which symptom indicates a client with inhalation anthrax is in the fulminant stage?

Pneumonic Plague

Pneumonic plague occurs in two forms, secondary and primary, both of which are frequently fatal and potentially contagious to close contacts.47,48 Secondary pneumonic plague is the more common form and arises through hematogenous spread of bacteria from a bubo or other source. Approximately 10% of all plague patients in the United States develop secondary pneumonic plague, usually as a result of delayed treatment of bubonic infections. Secondary pneumonic plague begins as an interstitial process with cough productive of scant, tenacious sputum, typically beginning 5 to 6 days after illness onset. Chest radiographs reveal diffuse alveolar infiltrates that are almost always bilateral and often accompanied by pleural effusions.49 If untreated, sputum will become more copious and eventually bloody, and death will often occur within 3 to 4 days.

Primary pneumonic plague is a fulminant condition that results from direct inhalation of bacteria into the lungs. This can occur through contact with another patient with pneumonic plague, exposure to animals (especially cats) with respiratory or pharyngeal plague, laboratory exposures, or, potentially, as a result of intentional aerosol release for purposes of terrorism. Symptoms begin within 1 to 4 days after exposure. Patients experience sudden onset of fever, chills, headache, malaise, and rapidly advancing tachypnea, dyspnea, hypoxia, chest pain, cough, hemoptysis, and general signs of endo­toxemia. Chest radiographs demonstrate a lobar pneumonia initially (Fig. 231-7), followed by dense consolidation and bronchopneumonic spread to other lobes of the same or opposite lung.30,50 Sputum is often purulent but may be watery, frothy, and copious and also may be blood tinged or grossly hemorrhagic, at which point it may contain large numbers of plague bacilli.47 Histologically, numerous bacilli and inflammatory cells fill the alveolar space (Fig. 231-8). Untreated pneumonic plague is almost always fatal, and mortality is very high in persons whose treatment is delayed beyond 24 hours after symptom onset. The case-fatality rate for pneumonic plague in the United States since 1950 approaches 50%.

To prevent person-to-person transmission, patients with suspected pneumonic plague should be managed in isolation under respiratory droplet precautions.12,51 Strict isolation under negative pressure and filtered exhausting is not necessary because infectious dispersal by fine aerosol or dried droplet nuclei does not occur. Person-to-person transmission of pneumonic plague requires close contact, typically with a patient who is in the late stages of infection and coughing copious amounts of bloody sputum.52 The last case of person-to-person respiratory spread in the United States occurred in Los Angeles in 1924. There have been at least nine subsequent cases of primary pneumonic plague, two resulting from laboratory exposures and others from exposures to domestic cats with respiratory plague, none of which resulted in transmission to other persons.30

Pneumonic Plague

Pneumonic plague is the most rapidly developing and life-threatening form of plague.1,6 The incubation period for primary pneumonic plague is usually 2–5 days (range 1–6 days). Illness onset is most often sudden, with chills, fever, body pains, headache, weakness, dizziness and chest discomfort. Cough, sputum production, increasing chest pain, tachypnea and dyspnea typically predominate on the second day of illness; hemoptysis, increasing respiratory distress, cardiopulmonary insufficiency and circulatory collapse can also occur. The sputum of primary plague pneumonia patients is typically watery or mucoid, frothy and blood tinged, and can be bloody. Initially, chest signs may indicate localized pulmonary involvement and a rapidly developing segmental consolidation can appear before bronchopneumonia occurs elsewhere in both lungs (Figure 126-5). Liquefaction necrosis and cavitation can develop at sites of consolidation and result in residual scarring.

Secondary pneumonic plague resulting from metastatic spread typically manifests as a diffuse interstitial pneumonitis with sputum production that is scant and more likely to appear tenacious and inspissated than the sputum of primary pneumonic plague patients.

Differential diagnostic possibilities include other bacterial conditions such as tularemia, mycoplasma pneumonia or other community-acquired bacterial pneumonias, Legionnaires' disease, Q fever and staphylococcal or streptococcal pneumonia. Viral pneumonias requiring differentiation include influenzal pneumonitis, hantaviral pulmonary syndrome and those caused by respiratory syncitial virus or cytomegalovirus infection.

Pneumonic Plague (Yersinia Pestis)

Pneumonic Plague—Fact Sheet

Pneumonic Plague—Pathologic Features

Pneumonic Plague

Pneumonic plague is a highly virulent form of plague with an incubation period from a few hours to 2–3 days. As few as 1 day after inhalation, the patient starts showing severe symptoms of pneumonia and could be dead the next day. Clinical presentation does not differ from pneumonia of other origins; however, a rapid course and high lethality are indicative of pneumonic plague.

Secondary plague pneumonia results from haematogenous spread of Y. pestis to the lungs, usually due to untreated or advanced infection of an initial bubonic or septicaemic form. A patient has usually been acutely ill for several days prior to lung invasion. Many patients die before they develop a well-advanced pneumonia. Those who do not die may be so sick that their cough reflex lacks the strength to produce finely aerosolized droplets. Consequently, during the early stages of disease, the risk of transmission is high.

Primary pneumonic plague is a rare but often fatal form of Y. pestis infection that results from direct inhalation of bacteria and is potentially transmissible from person-to-person and has the potential for propagating epidemics. The onset of pneumonic plague is most often sudden (with chills, fever, headache, body pains, weakness, dizziness, and chest discomfort) (Figure 33.3). Sputum is mucoid at first, rapidly develops blood specks, and then becomes uniformly pink or bright red and foamy. Tachypnoea and dyspnoea are present on the second day of illness, but pleuritic chest pain is not. Signs of consolidation are rare, and rales may be absent.

This form of the infection evolves rapidly, spreads more easily from person to person, and is far more deadly, killing 100% of those who do not receive the appropriate antibiotics soon after exposure.

Pneumonic Plague

Pneumonic plague occurs in two forms, primary and secondary, both of which are potentially contagious and frequently fatal.5,50 Primary plague results from direct inhalation of plague bacteria into the lungs. Onset is sudden with chills, high fever, headache, body pains, weakness, dizziness, and chest discomfort. Cough, sputum production, increasing chest pain, tachypnea, and dyspnea typically predominate on the second day of illness and may be accompanied by hemoptysis, increasing respiratory distress, cardiopulmonary insufficiency, cyanosis, and circulatory collapse. Principally an alveolar process, primary pneumonic plague is characterized by sputum that is initially watery or mucoid, and quickly becomes blood-tinged or frankly bloody. Chest signs in primary plague pneumonia may indicate localized pulmonary involvement in the early stage, with rapidly developing segmental consolidation before bronchopneumonia spreads to other segments and lobes of the same and opposite lung. Liquefaction necrosis and cavitation may develop at sites of consolidation and may leave significant residual scarring.

Secondary pneumonic plague arises through hematogenous spread from a bubo or other untreated source. It manifests first as an interstitial pneumonitis in which sputum production is scant, and the sputum is more likely to be inspissated and tenacious in character than the sputum found in primary pneumonic plague. In the United States from 1960 to 2008, 55 cases of secondary plague pneumonia and 11 cases of primary plague pneumonia were reported to the CDC, with no known secondary transmission to contacts and an overall case-fatality rate of 42% (CDC, unpublished data, 2009). Observers of pneumonic plague in the early twentieth century remarked on minimal auscultatory findings, the appearance of toxemia, and the frequency of sudden death, as compared to patients with other bacterial pneumonias.50 Differential diagnostic possibilities include other bacterial pneumonias such as mycoplasma pneumonia, legionnaires’ disease, staphylococcal or streptococcal pneumonia, tularemia pneumonia, and Q fever. Severe viral pneumonia, including hantavirus pulmonary syndrome and SARS, could be confused with plague.

Because respiratory spread of Y. pestis occurs by infective droplets, only persons with close respiratory exposure have a high risk of infection. Primary plague pneumonia is considered more contagious than secondary pneumonia because it is more likely to produce copious watery sputum, and the patient may be mobile and expose a wider circle of individuals in the early stage of contagiousness.

PNEUMONIC PLAGUE

Laboratory diagnosis

Pneumonic plague is easily acquired in the laboratory by inhalation of aerosols generated from Y. pestis cultures. These and clinical specimens suspected of containing the organism should be handled only under containment conditions appropriate for hazard group 3 pathogens. Animals used for diagnostic tests must be housed under insect-free containment conditions and handled with strict precautions.

Plague is confirmed by demonstrating the bacilli in fluid from buboes or local skin lesions in the case of bubonic plague, in the sputum in pneumonic plague, and in blood films and by blood culture when septicaemic plague is suspected. Blood culture may be intermittently positive in all forms of the disease. Post mortem, the bacilli can usually be isolated from a wide range of tissues, especially spleen, lung and lymph nodes.

Smears of exudate or sputum are stained with methylene blue, Wayson stain (a mixture of basic fuchsin, methylene blue and phenol), Giemsa stain or with an immunospecific stain. Characteristic bipolar-stained coccobacilli are confirmed as Y. pestis by culturing samples on blood agar and incubating at 27°C. If exudate is inoculated subcutaneously into guinea-pigs or white rats, or on to their nasal mucosa, infection follows and the animals die within 2–5 days. The bacilli may then be isolated from the blood or from smears of spleen tissue taken post mortem.

Characteristic colonies growing on blood agar plates are identified presumptively by various cultural and biological tests, by demonstrating chain formation in broth culture, and by ‘stalactite’ growth from drops of oil layered on the surface of fluid medium. Demonstration of the F1 capsular antigen by immunospecific staining confirms the presence of Y. pestis except in the case of rare non-capsulate strains.

Serology is most likely to be useful in the convalescent stage. The complement fixation and a haemagglutination tests formerly used have now been largely superseded by an enzyme-linked immunosorbent assay (ELISA) with F1 antigen.

A polymerase chain reaction (PCR), with primers based on F1 gene sequences, offers a rapid and less hazardous means of diagnosis than culture.

Yersinia pestis

Primary pneumonic plague follows inhalation of Y. pestis bacilli in a potential bioterrorism scenario.100,101 The infection begins as bronchiolitis and alveolitis that progress to a lobular and eventual lobar consolidation.102 The histopathologic features evolve over time, beginning with a serosanguineous intraalveolar fluid accumulation with variable fibrin deposits (Fig. 7.40), progressing through a fibrinopurulent phase, and culminating in a necrotizing lesion.103 The presence of myriad bacilli in the intraalveolar exudates with significantly fewer organisms in the interstitium (a characteristic of primary pneumonia) is one of several pulmonary and extrapulmonary features used to distinguish primary from secondary pneumonic plague.104 These bacilli may be obvious in H&E-stained sections (Fig. 7.41) but generally are better visualized with Giemsa rather than Gram stain. Immunohistochemical staining provides a rapid and specific diagnosis.102 In contrast to inhalational anthrax, sputum Gram stain and culture are useful tests that are likely to yield a positive result at clinical presentation. Also, because sepsis is an integral component of the pneumonia, it is important to collect blood culture specimens.105

Post-Incident actions

All cases of pneumonic plague should be considered terrorism-related until proven otherwise. Hospital infection control officers and local and state, national health, and law enforcement officials should be notified immediately of any suspected cases of the plague.

The risk for reaerosolization of Y. pestis from the contaminated clothing of exposed persons is low. Under ideal conditions, Y. pestis can survive in the environment for about 1 hour, and since patients will present with symptoms after 24 hours, there is no need for routine decontamination. In situations where there may have been recent, gross exposure to Y. pestis, decontamination of skin and potentially contaminated fomites (e.g., clothing or environmental surfaces) may be considered to reduce the risk of cutaneous or bubonic forms of the disease.

The plan for decontaminating patients may include several steps. Patients should be instructed to remove contaminated clothing. Clothing should be stored in labeled, plastic bags and gently handled to avoid dispersal of Y. pestis. Patients should be instructed to shower thoroughly with soap and water. Environmental surface decontamination may be performed using an Environmental Protection Agency-registered, facility-approved sporicidal/germicidal agent or a 0.5% hypochlorite solution (one part household bleach added to nine parts water).1,19,20 In addition to standard decontamination procedures, chlorine dioxide gas has been shown to rapidly deactivate almost 100% of Y. pestis in a hospital environment, but further studies are needed regarding safe usage.21

In its natural form, pneumonic plague is transmitted person to person via large droplets (not via fine-particle aerosol), and it requires close personal contact (2 m or less) for effective transmission.5,22,23 Patients with symptoms suggestive of pneumonic plague should be isolated using droplet precautions in addition to standard precautions. Patients with suspected pneumonic plague should be placed in a private room when possible. It is appropriate to cohort symptomatic patients with similar symptoms and the same presumptive diagnosis (i.e., pneumonic plague) when private rooms are not available. Maintain spatial separation of at least 3 feet between infected patients and others when cohorting is not possible. Avoid placement of patients requiring droplet precautions in the same room with an immunocompromised patient. Special air handling is not necessary, and doors may remain open. Patient transport should be limited to essential medical purposes. When transport is necessary, minimize dispersal of droplets by placing a surgical-type mask on the patient. Isolation precautions should be continued for 2 days after initiation of antibiotics and until some clinical improvement occurs in patients with pneumonic plague.9

4.2 Therapeutics

Persons in contact with pneumonic plague patients or handling potentially infectious body fluids or tissues should receive antibiotic preventive therapy within 6 days. The preferred antibiotics for prophylaxis are tetracyclines or chloramphenicol.

If plague is suspected, antibiotic treatment must be started immediately without waiting for laboratory confirmation and patients must be placed in isolation to reduce the risk of spread in the event of pneumonic plague developing. In the past, streptomycin has been the drug of choice for treatment of plague, particularly the pneumonic form. The daily dose of 2 g daily is recommended for adults, given intramuscularly for up to 10 days. Care must be taken to avoid inducing endotoxic shock as streptomycin is bacteriolytic. Gentamycin is another aminoglycoside which has been used to treat plague. Due to the toxicity of streptomycin, patients are usually moved onto another antibiotic, usually tetracycline, 3 days after their temperature has returned to normal. Tetracycline is bacteriostatic but effective in treatment of uncomplicated plague. A further advantage of tetracycline is that it can be given orally. In cases of plague meningitis, chloramphenicol is the drug of choice due to its tissue penetration. Daily doses of 50 mg/kg can be given parenterally or orally for up to 10 days. Fluoroquinolones such as ciprofloxacin, gatifloxacin, and moxifloxacin have been shown to be therapeutic in laboratory animals (Byrne et al., 1998; Russell et al., 1998; Steward et al., 2004), but so far this class of antibiotic has rarely been used to treat human plague, although ciprofloxacin does appear effective (Kuberski, Robinson, & Schurgin, 2003) and ciprofloxacin is now included in CDC guidelines with a recommended dose of 400 mg given intravenously or 500 mg orally, twice a day (Inglesby et al., 2000). Other classes of antibiotics, such as penicillins, cephalosporins, and macrolides, have been shown to be ineffective in treatment of plague. Antibiotic resistant strains are rare, but a multiply antibiotic-resistant strain was isolated in Madagascar (Guiyoule et al., 2001) and efficient transfer of resistance genes to Y. pestis in the midgut of the flea has been demonstrated (Hinnebusch, Rosso, Schwan, & Carniel, 2002).