By Dr: WALEED FOUAD LECTURER OF TROPICAL MEDICINE Plague By Dr: WALEED FOUAD LECTURER OF TROPICAL MEDICINE

Definition Plague is a bacterial disease, caused by Yersinia pestis, which primarily affects wild rodents. Also known as bubonic plague, black plague, and the Black Death.

Humans bitten by an infected flea usually develop a bubonic form of plague, which is characterized by a bubo, i.e. a swelling of the lymph node draining the flea bite site. If the bacteria reach the lungs, the patient develops pneumonia (pneumonic plague), which is then transmissible from person to person through infected droplets spread by coughing. Pneumonic plague, on the other hand, is one of the most deadly infectious diseases; patients can die 24 hours after infection.

Etiology Y. pestis is a pleomorphic, non–spore-forming, gram-negative, bipolar-staining coccobacillary member of the family Enterobacteriaceae. It is a nonmotile, facultative anaerobe that is able to grow aerobically on routine microbiologic media. The organism can survive at room temperature in dried blood or the environment for weeks to months. Y. pestis is one of the most virulent bacteria known.

Transmission Yersinia infections primarily affect rodents, pigs, and birds. It is spread from one rodent to another by fleas. Humans are accidental hosts. It is transmitted between animals and humans by: Bite of infected fleas. Bites or scratches from an infected animal. Direct contact with infected tissues or body fluids. Inhalation of aerosolized bacilli. Rarely, ingestion of infective materials.

Male Xenopsylla cheopis (oriental rat flea) engorged with blood Male Xenopsylla cheopis (oriental rat flea) engorged with blood. Primary vector of plague in most large plague epidemics in Asia, Africa, and South America. Both male and female fleas can transmit the infection.

Epidemiology Human plague is now relatively infrequent worldwide. Aerosolized Y. pestis is well recognized for its potential use as a biological weapon. Plague currently exists in widely scattered foci in Asia, Africa, and the Americas.

In Africa, human plague was reported in 4 countries (Madagascar, Mozambique, Uganda and Zimbabwe) in 1998 with total number of cases representing 95 % of the world total. In 1999, 5 countries (Madagascar, Malawi, Mozambique, Namibia and United Republic of Tanzania) with total number of cases representing 98.4% of the world total. In 2003, 9 countries reported 2118 cases and 182 deaths 98.7% of those cases and 98.9% of those deaths were reported from Africa.

Current status There is a suspected outbreak of bubonic plague in Libya (last outbreaks of plague in Libya in the 1970s and 1980s). The disease appeared in a Libyan village 50km from the border with Egypt. 12 cases have been reported, together with one death. It is thought the disease is a result of rising numbers of rats attracted by livestock being reared near homes.

Pathogenesis Organism inoculated through the skin or mucous membranes Invades cutaneous lymphatics Monocytes and macrophages phagocytize Y. pestis without killing it, spreads infection from the inoculation site

Bacteria enter the bloodstream Infected lymph nodes are tender and edematous Initially Hemorrhagic necrosis develops in affected nodes Later Liver Spleen Lungs CNS Bacteria enter the bloodstream

Clinical Manifestations Clinical plague infection manifests itself in three forms depending on the route of infection: Bubonic. Septicaemic. Pneumonic.

Bubonic plague Bubonic form is the most common form of plague resulting from the bite of an infective flea.

The usual incubation period for bubonic plague is 2 to 3 days. Acute illness characterized by Abrupt onset of fever, chills, headache. Gastrointestinal symptoms. Local pain, followed within hours by the development of a painful, swollen mass of lymph nodes (buboes) in the groin or axilla.

Skin overlying buboes is usually red-purple in color Skin overlying buboes is usually red-purple in color. Buboes are initially tense and hard but rapidly become fluctuant. Spontaneous rupture and drainage can occur.

Bubonic plague infection causes tiny blood vessels in the feet and toes to clog up and cut off circulation. Without blood, the flesh dies and turns black (called "gangrene"). This is why in the Middle Ages bubonic plague was called "the Black Death."

Septicaemic plague Occurs when infection: Spreads directly through the bloodstream without evidence of a "bubo". More commonly advanced stages of bubonic plague. Flea bites. Direct contact with infective materials through cracks in the skin.

Buboes do not develop in patients with septicemic plague. Patients have gastrointestinal signs and symptoms: Nausea & vomiting. Diarrhea. Abdominal pain. There may be signs of meningitis.

Pneumonic plague The most virulent and least common form of plague. Pneumonic form is due to: Secondary spread from advanced infection of an initial bubonic form. Primary pneumonic plague results from inhalation of aerosolized infective droplets and can be transmitted from human to human without involvement of fleas or animals.

The usual incubation period for pneumonic plague is 2 to 3 days. Patients usually present with: Tachypnea . Productive cough. Blood-tinged sputum. Cyanosis. Primary plague pneumonia is usually fatal and present as fulminant pneumonitis with bloody, frothy sputum and sepsis.

Laboratory Diagnosis TLC --» elevated 15,000 - 25,000 cells/μl, with a shift to the left Leukemoid reactions (> 50,000 cells/μl) can occur. Platelet count may be normal or mildly depressed or may be very low if DIC is present. Fibrin split products is frequently elevated. Hepatic aminotransferases and bilirubin are often increased.

Confirmation Recovery and identification of Y. pestis culture from: Bubo aspirates. Blood. Sputum. The organism can be easily grown on: Blood agar. MacConkey agar. infusion broth.

Serology Serum taken during the early and late stages of infection can be examined to confirm infection. Direct immunofluorescence (Rapid dipstick test) quickly screen for Y. pestis antigen in patients. Passive hemagglutination test.

Treatment Plague can be a very severe disease in people, with a case-fatality ratio of 30%-60% if left untreated. Drug of choice: Streptomycin (30 mg/kg I.M. in divided doses every 12 hours) reduces mortality to approximately 5%. Gentamicin (more widely available than streptomycin) also appears to be effective. To prevent relapses, antibiotic treatment should be continued for 10 days or for at least 3 days after defervescence and clinical recovery. Most patients improve rapidly and defervesce within 72 hours of initiation of antimicrobial therapy, although buboes can persist for weeks.

Some authorities advocate switching from streptomycin to a different antibiotic for completion of therapy after 5 days of treatment in order to minimize the risk of ototoxicity and nephrotoxicity. Tetracycline or doxycycline can also be used for plague. Chloramphenicol is the preferred agent for plague meningitis, pleuritis, endophthalmitis, and myocarditis because of superior penetration into those tissues. Penicillins, cephalosporins, & macrolides are suboptimal. Trimethoprim-sulfamethoxazole & fluoroquinolones appear to be active against plague in vitro, but clinical experience is limited.

Prevention The objective of preventive measures is to: Inform people to be aware of the areas where zoonotic plague is active. Take precautions against flea bites and handling carcass while in plague-endemic areas. Avoid direct contact with infective tissues. Avoid exposure to patients with pneumonic plague.

Chemoprophylaxis Indications: Regimen: Contacts of patients with pneumonic plague. Contacts of patients with suspected septicemic plague with pulmonary involvement. Regimen: Tetracycline (500 mg p.o., q.i.d.) or doxycycline (100 mg p.o., b.i.d.). Streptomycin (20 mg/kg/day I.M. in two divided doses) or trimethoprim-sulfamethoxazole (40 mg/kg p.o., b.i.d.) can be used for children younger than 8 years.

Vaccination Plague vaccine (Cutter Laboratories) is a killed, formalin/phenol- fixed whole-bacteria vaccine that provides only partial protection against infection. Vaccinated individuals who are exposed to plague should still receive chemoprophylaxis. Vaccines are not recommended for immediate protection in outbreak situations but only recommended as a prophylactic measure for high-risk groups (e.g. laboratory personnel who are constantly exposed to the risk of contamination).

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