Detailed Notes on Category B Bacteria: Brucella, Coxiella, Burkholderia, Vibrio, Salmonella, Escherichia, and Shigella

Category B Bacteria

• According to the CDC, Category B bacteria include:

  • Brucella sp.

  • Burkholderia mallei

  • Vibrio cholerae

  • Coxiella burnetii

  • Salmonella sp.

  • Escherichia coli O157:H7

  • Shigella sp.

Presentation Information

• Created by: Dr. Magdalena Florek and Dr. hab. Jarosław Król, employees of the Wrocław University of Environmental and Life Sciences.

• Intended for: ED students of the III year of the Faculty of Veterinary Medicine in Wrocław and Erasmus students.

• Purpose: For teaching purposes only.

• Copyright protection: Further dissemination, recording, copying, or making changes is prohibited.

EU One Health Zoonoses Report 2018

• The report includes data on several zoonoses:

  • Campylobacteriosis

  • Salmonellosis

  • STEC infections (N = 8,161)

  • Yersiniosis (N = 6,699)

  • Listeriosis (N = 2,549)

  • West Nile fever (N = 1,548)

  • Echinococcosis (N = 793)

  • Q fever (N = 789)

  • Brucellosis (N = 358)

  • Tularaemia (N=300)

  • TB caused by M. bovis (N=170)

  • Trichinellosis (N = 66)

  • Rabies (N = 1)

• The majority of the bacterial agents classified as category B are readily available in nature as they are responsible for numerous infections in humans and animals.

• Regardless of their origin (human pathogens like Vibrio, or zoonotic bacteria of animal origin, e.g., Brucella, Coxiella), these pathogens can produce diseases in humans with moderate morbidity, requiring specific enhancements in diagnostic capacity and enhanced disease surveillance.

• Reference: https://www.ecdc.europa.eu/sites/default/files/documents/zoonoses-EU-one-health-2018-report.pdf

Brucellosis

• Human infections are mainly caused by Brucella melitensis, B. suis, B. abortus, and B. canis.

• These are small gram-negative coccobacilli that grow within macrophages and other host cells (intracellular parasites).

• Routes of exposure:

  • Alimentary (mostly by ingestion of unpasteurized dairy products, raw meat).

  • Through broken skin and conjunctivas.

  • Inhalation of infected aerosols (effective infectious dose is 10-100 cells).

• Primary reservoirs are goats, cattle, sheep, pigs, camels, elks, caribou, bison, deer, wild, and domestic canines.

Brucellosis in Europe (ECDC)

• In 2019, 314 cases of human brucellosis were reported in the EU.

• Reference: https://atlas.ecdc.europa.eu/public/index.aspx?Dataset=27&HealthTopic=48

Brucellosis in Humans - Clinical Symptoms

• Incubation period: 5 days to 2 months.

• Clinical course and severity of the disease are diverse.

• Three forms of brucellosis:

  • Acute (systemic, febrile illness).

  • Insidious chronic infection.

  • Localized inflammatory process.

• Symptoms begin as an acute illness with few or no localized signs and may progress to a chronic stage with relapses of fever, weakness, sweats, and vague aches and pains.

• B. melitensis tends to cause more severe, systemic illness than other Brucella species.

• B. suis is more likely to cause localized suppurative disease.

Brucellosis in Humans - Generalized Clinical Symptoms

• Fever (usually undulant), malaise, sweats, fatigue, muscle and joint aches.

• Neuropsychiatric symptoms:

  • Depression, headache, irritability occur frequently as a result of neurotoxic process.

• Bone and joint disease:

  • Sacroiliitis, arthritis of large joints, spondylitis (in middle-aged or elderly patients) causing back (lumbar) pain, local tenderness, and radicular symptoms (spinal nerve root pathology caused by compression or irritation of nerve roots (anesthesia, paresthesia, hypoesthesia, motor loss and/or pain)).

• Infection of the genitourinary tract:

  • Pyelonephritis, cystitis, epididymo-orchitis.

• GI symptoms:

  • 70% of patients report anorexia, nausea, vomiting, abdominal pain, diarrhea/constipation.

• Respiratory symptoms:

  • Cough, dyspnea, or pleuritic pain.

Brucellosis - Complications and Recovery

• Complications are rare but include:

  • Subacute bacterial endocarditis (rare but feared complication, accounts for 80% of deaths from brucellosis).

  • Neurobrucellosis (includes acute and chronic meningitis, encephalitis, and neuritis).

  • Cholecystitis, hepatic suppuration, and osteomyelitis (particularly sacroiliac or vertebral).

• Patients with acute, uncomplicated brucellosis usually recover in 2 to 3 weeks, even without treatment.

• Some go on to subacute, intermittent, or chronic disease.

• Recovery may occur after 1-2 years, but in chronic cases, the disease may last for 20 years, showing episodes of intensification and alleviation of symptoms.

• Overall mortality rate – 2-5%.

Brucellosis – Treatment and Prophylaxis

• Laboratory diagnosis:

  • Acute and convalescent serology (samples taken 3 weeks apart; ELISA and Western blot, serum agglutination test; a 4-fold increase or an acute titre of 1:160 or higher is considered diagnostic).

  • Culture from blood, bone marrow, CSF other tissues (slow growth – may require 30-40 days; high risk to the laboratory workers).

  • PCR (from blood/tissues, can be positive as early as 10 days after inoculation).

• Therapy with a single drug has resulted in a high relapse rate, so usually combined antibiotic therapy with 2-3 preparations is used.

  • Doxycycline plus either rifampin, aminoglycoside (streptomycin or gentamicin), or ciprofloxacin for 2-6 weeks.

  • Neurobrucellosis and endocarditis require longer treatment.

• Recurrence of the disease may occur despite treatment.

Brucellosis – Vaccine, Prophylaxis and Immunity

• No commercially available vaccine exists for humans, and the use of the animal vaccine (a live-attenuated preparation containing B. abortus strain RB51) in humans can cause infection.

• Post-exposure prophylaxis is recommended for high-risk patients (those who have unprotected exposure to infected animals or laboratory samples or who received animal vaccine).

  • Doxycycline plus rifampicin for 3 weeks (rifampin is not used for exposure to the vaccine strain, which is resistant).

• Transmission from human-to-human is rare (breastfeeding, sexual, blood transfusion, or transplantation).

• Immunity after human infection is short-lived, lasting about 2 years.

Brucellosis as a Biological Weapon

• In the fifties and sixties, the US military did extensive research on Brucella suis and developed a way to 'weaponize' the pathogen.

  • They created extensive stocks of artillery and bombs (armed with 'a bacterium that causes a debilitating flu-like disease in humans’) that were destroyed when the Army abandoned its biological weapons program in 1969.

• Brucellosis is rarely fatal for humans, but it is highly contagious, difficult to treat, and spreads easily; disease progress is long and incapacitating.

• Bacteria reside quiescently in tissue and bone-marrow and are extremely difficult to eradicate even with antibiotic therapy.

• A vaccine for humans is not available.

• The initial symptoms of brucellosis are usually nonspecific, and the differential diagnosis is therefore very broad.

• Laboratory infections are quite common, but human-to-human transmission is rare.

• The organisms are readily lyophilized, perhaps enhancing their infectivity.

• Under selected environmental conditions, persistence for up to 2 years has been documented.

• When used as a biological warfare agent, Brucella would most likely be delivered by the aerosol route; the resulting infection would be expected to mimic natural disease.

Q Fever

• Etiologic agent: Coxiella burnetii, small pleomorphic rod (0.4-1\mu m); its cell wall is similar to that seen in Gram-negative bacteria but is difficult to stain with Gram’s method.

• The “Q” comes from “query” fever, the name of the disease until its true cause was discovered in the 1930s.

• C. burnetii exists in two antigenic phases, phases I and II. In animals, it exists in phase I and is extremely infectious.

• Coxiella burnetii can form a spore able to survive for extended periods (in temperature 15-20°C up to 1 year) in hostile environments.

• It is markedly resistant to physiochemical agents (environmental stresses such as high temperature, osmotic pressure, and ultraviolet light, drying, even some disinfectants).

Q Fever - Epidemiology

• Coxiella burnetii infections are identified in at least 51 countries and on 5 continents.

• For 2019, 1069 cases of Q fever were reported in the EU; a seasonal pattern of the disease was observed involving an increase in case numbers during the spring and summer months (ECDC).

• Reference: https://atlas.ecdc.europa.eu/public/index.aspx?Dataset=27&HealthTopic=48

Q Fever - Reservoirs, Transmission, and Infectious Dose

• Sheep, cattle, and goats serve as reservoirs of the agent (it can also exist in other mammals, birds, fish, and arthropods).

• Animal infections are predominantly asymptomatic.

• Humans have been infected most commonly by contact with domestic livestock (risk of infection increases during parturition – a large amount of C. burnetti multiplied in the placenta is released in the form of infectious aerosol) and other domestic animals (dogs, cats).

• Routes of infection:

  • Inhalation (aerosol of dried animal secretions and excretions, especially amniotic fluid and fetal membranes).

  • Alimentary route (unpasteurized milk).

  • Tick bite (uncommon in humans).

• Infectious dose: a single organism can initiate infection.

Q Fever - Clinical Manifestations and Mortality

• Incubation period: 2-40 days (depends on magnitude of inoculum).

• Q fever in humans may be manifested by asymptomatic seroconversion, acute illness, or chronic disease.

• Acute form (lasts from 2 days to 3 weeks):

  • Flu-like symptoms; most patients appear mildly to moderately ill; however, in some cases pneumonia, hepatitis, encephalitis, and meningitis may follow.

  • Pregnant women may be at risk for miscarriage, stillbirth, pre-term delivery, or low infant birth weight.

  • Although the majority of people with acute Q fever recover completely, a post-Q fever fatigue syndrome has been reported to occur in up to 20% of patients with acute Q fever. It is characterized by constant or recurring fatigue, night sweats, severe headaches, photophobia, pain in muscles and joints, mood changes, and difficulty sleeping.

• Mortality rate is low (3-4%), the disease is self-limited.

• Rarely, in 1 to 5% of cases, the disease progresses into chronic form (manifests within few days to years after the initial infection), in which most severe complication is endocarditis; hepatitis and osteomyelitis may also occur. Mortality rate rises to 65%.

Q Fever - Laboratory Diagnosis

• Immunofluorescence assay of infected tissue is the diagnostic method of choice; alternatively, enzyme-linked immunosorbent assay (ELISA) may be done.

• Acute and convalescent serum specimens (typically complement fixation) may be used. Antibodies to phase II antigen are used to diagnose acute disease, and antibodies to both phase I and phase II antigens are used to diagnose chronic disease.

• PCR on whole blood or tissues can identify the organism, but negative results do not rule out the diagnosis.

• Culture isolation of C. burnetii is not recommended for routine diagnosis because it is difficult, time-consuming, and is only available at specialized laboratories (BSL-3).

Q Fever - Treatment

• Considering the risk of the life-threatening complications, all patients with confirmed or suspected C. burnetii infection should be treated with antibiotics.

• Treatment should be initiated as soon as Q fever is suspected and should never be withheld pending the receipt of diagnostic test results.

• Doxycycline is the recommended first-line treatment for non-pregnant adults (also for children; pregnant women - trimethoprim/sulfamethoxazole) and is most effective at preventing severe complications if it is started within the first 3 days of symptoms.

  • If patient remains febrile past 5 days of doxycycline treatment, trimethoprim/sulfamethoxazole should be used.

• In acute form typically 2 to 3 weeks of treatment is required. Duration of treatment for chronic Q fever is based on serologic response and evidence of clinical improvement. For endocarditis, treatment needs to be prolonged (months to years to lifelong), typically for at least 18 months.

• Treatment is generally not recommended for patients who are asymptomatic but might be considered for those at high risk of developing chronic Q fever.

Q Fever - Treatment and Prophylaxis

• There is no role for prophylactic antimicrobial agents in preventing Q fever after a known, naturally occurring exposure and prior to symptom onset; attempts at prophylaxis will likely extend the incubation period by several days but will not prevent infection from occurring.

• The vaccine (Q-Vax) containing live, attenuated C. burnetti strains is commercially available in Australia and Eastern Europe.

• Vaccination with a single dose provides complete protection against naturally occurring Q fever and >90% protection against experimental aerosol exposure in human volunteers. Protection lasts for at least 5 years.

• In Australia, vaccination is recommended to protect people with occupational risk (slaughterhouse and dairy workers, rendering-plant workers, herders, wool sorters, farmers).

• Administration of this vaccine may cause severe cutaneous reactions including necrosis at the inoculation site, therefore pre-vaccination screening with skin and blood tests should be done to identify pre-existing immunity to Q fever, because vaccinating people who already have immunity can cause the severe local reactions.

Q Fever as a Biological Weapon

• Bacterium available worldwide.

• Is a highly infectious agent that is resistant to heat, drying, and many common disinfectants.

• It can be aerosolized and inhalation is the primary route of infection for people.

• As few as 1-10 C. burnetii organisms may cause disease in a susceptible person.

• Highly incapacitating.

• This agent has been previously weaponized for use in biological warfare.

• The WHO has estimated that if 50 kg of C. burnetii were aerosolized over an urban area with 500,000 inhabitants, there would be 125,000 cases of acute illness, 9,000 cases of chronic Q fever, and 150 fatalities.

• Person to person transmission is possible (but rare) via transplacental exposure, sexual contact, blood transfusion, and transplantation. Nosocomial infections have been rarely reported following autopsies and obstetrical procedures involving infected persons.

• Clusters of pneumonia, or unusual clusters of acute febrile illness with respiratory involvement or granulomatous hepatitis, in a community where no other cause can be identified may indicate a possible intentional release of C. burnetii.

• In cases of suspected intentional release, post-exposure prophylaxis (doxycycline for 5-7 days) can be considered in groups determined to be at high risk for exposure but is not recommended for the prevention of naturally occurring Q fever. Chemoprophylaxis is only considered effective if administered within 8-12 days of exposure.

Glanders

• Etiologic agent: Burkholderia mallei.

• The disease occurs primarily in odd-toed ungulate animals (horses, donkeys, mules) and felidae.

• Glanders has been eradicated in North America, Australia, and Europe through testing and then eliminating any infected animals, coupled with import control measures. However, it remains sporadically reported in a number of Asian, African, Middle Eastern, and South American countries.

• Glanders is zoonotic and is transmitted to humans by direct contact with sick animals or infectious materials or through ingestion of glandered meat.

• Cases of person-to-person transmission have been noticed.

• Routes of infection: alimentary, inhalation, broken skin, and mucosa.

Glanders in Humans

• Incubation period: 1-14 days.

• Generalized symptoms include: fever, myalgia, chest pain, headache, malaise, nasal discharge, light sensitivity (sometimes with excessive tearing of the eyes).

• Human disease can manifest as:

  • Acute localized infection:

    • Skin infection – 1-5 days after infection local ulcerative lesions with enlarged regional lymph nodes are present.

    • Mucous membrane infection manifests as nasal ulcers and nodules that secrete bloody discharge, increased mucus production from the affected sites. Dissemination to other locations in the body may occur 1-4 weeks after infection.

  • Acute pulmonary infection (pneumonia, pulmonary abscesses, pleural effusion) can result from inhalation or hematogenous spread.

  • Chronic form (necrotizing granulomas in the liver and spleen, and muscles of arms and legs; skin abscesses).

  • Bacteremia accompanied by signs of sepsis as well as presence of abscesses (throughout the body) and multiple cutaneous pustules. Without treatment, glanders bloodstream infections are usually fatal within 7 to 10 days.

• High mortality rate – approaching 50% in treated and 95% in untreated patients.

Glanders – Treatment and Prophylaxis

• Laboratory diagnostic: Gram staining, bipolar staining with methylene blue/Wright; culture (slow growth on nutrient agar); agglutination test, CF.

• Treatment: varies with the type and severity of the clinical disease. Severe cases require initial parenteral therapy with subsequent prolonged oral antibiotic therapy for many months (it is required to prevent relapse); combined antibiotic therapy typically is used (e.g., ceftazidime + trimethoprime-sulfametoxazole, imipenem + doxycycline). Though individual susceptibility testing for each strain is required, the bacterium is usually susceptible to: sulfadiazine, tetracyclines, ciprofloxacin, streptomycin, novobiocin, gentamicin, imipenem, ceftrazidime, sulfonamides.

• As post-exposure antibiotic prophylaxis, trimethoprime-sulfametoxazole and amoxiclav are recommended; antibiotics should be administered for 21 days.

• There is no vaccine available for human use.

Glanders as a Biological Weapon

• During World War I, German agents used the bacterium on horses, mules, and livestock (in order to disorganize transportation and shorten food supplies) in the United States, Romania, Spain, Norway, and Argentina; during WWII it was tested on horses, civilians, and prisoners of war (Unit 371).

• It has been weaponized during various bioweapons programs: USA (40’ and 50’), Japan (WWII), and SU (after WWII).

• Between 1982 and 1984, the SU allegedly used weaponized B. mallei during the Soviet-Afghan War.

• Burkholderia mallei is easy to culture.

• It has a low infectious dose – so few organisms are necessary to cause disease.

• Infection via aerosol is possible.

• Human disease is severe and mortality rate relatively high.

• Human-to-human transmission is possible.

• Laboratory diagnostic (esp. culture) requires BSL-3 laboratories.

• B. mallei cannot persist in the environment outside its host.

Cholera

• An acute, diarrheal disease of the gastrointestinal tract of humans caused by Vibrio cholerae. The disease is severe incapacitating and resource-intensive but generally not deadly unless therapy is not provided.

• Cholera is caused by ingestion of contaminated food and water as well as by contact with ill person or carrier.

• Humans are the only relevant reservoir, even though vibrios can survive for a long time in coastal waters contaminated by human excreta.

• The disease has occurred for several hundreds of years in Asia; it was spread to other parts of the world (from 70’– Africa; 90’- South and Central America – Peru, Haiti). In Europe, each year importations of the disease are noticed. The annual burden of cholera has been estimated at 1.3 to 4.0 million cases and 21,000 to 143,000 deaths worldwide (2017, WHO).

• On the basis of its antigenic composition (somatic antigen O), V. cholerae is divided into more than 200 serotypes. Cholera outbreaks are caused mainly by serotype O1 (El Tor and classical biotypes) as well as O139 (Bombay).

Cholera - Epidemiology (ECDC)

• In 2019, 26 cases of Cholera were reported in the EU.

• Reference: https://atlas.ecdc.europa.eu/public/index.aspx?Dataset=27&HealthTopic=48

Cholera - Transmissibility

• Infectious dose: 10 to 500 organisms.

• In order to be an effective BW, major drinking supplies would need to be heavily contaminated.

• Diarrheal fluids are highly infective.

• The organism is easily killed by desiccation.

• It is not viable in pure water; it may survive 24h in sewage and as long as 6 weeks in water containing organic matter.

• It is eliminated by modern sewage and water treatment systems.

Cholera – Clinical Symptoms

• Incubation period: ranges from four hours to 5 days.

• In most cases, symptoms are mild or absent (and infected individuals become asymptomatic carriers).

• Approximately 1 in 20 infected persons has severe disease.

• Clinical symptoms: sudden onset of vomiting, followed rapidly by watery diarrhea with „rice water” appearance; usually without abdominal pain and fever.

• Fluid loss may exceed 5 to 10 liters a day; severe dehydration, hipokalemia, and metabolic acidosis develop rapidly.

• Symptoms of severe dehydration:

  • Sunken eyes, a dry mouth, loss of skin elasticity

  • Facies cholerica (the face is excessively disfigured, sunken, pale or livid, cadaverous, with cold, bluish tip of the nose)

  • Hypovolemic shock and renal failure

  • Coma or seizures

• Mortality rate is 1-20% in case of appropriate treatment and approximately 50% in untreated ones.

Cholera - Treatment

• Rehydration – per os (for every 1 l of water: sodium chloride – 3.5 g, sodium citrate – 2.9 g, potassium chloride – 1.5 g, glucose – 20.0g; WHO Oral Rehydration Solution) or rapid aggressive intravenous administration of fluids.

• Antibiotics: the antibiotic therapy is indicated for severe cases of cholera; tetracyclines (drugs of choice – doxycycline (adults) and azithromycin (children and pregnant women) – first line treatment); as alternative ciprofloxacin, trimethoprim-sulfametoxazole. Antibiotics shorten the duration of the diarrhea and the shedding period.

• Zinc treatment has also been shown to help improve cholera symptoms in children.

Cholera - Prophylaxis

• Post-exposure antibiotic treatment: tetracycline/doxycycline for 3 days.

• Currently, there are three WHO pre-qualified oral cholera vaccines: Dukoral, Shanchol, and Euvichol. All require two doses for full protection. Dukoral provides protection against cholera for 2 years, while Shanchol and Euvichol - for 3 years.

• The FDA recently approved a single-dose live oral cholera vaccine called Vaxchora®; it has been reported to reduce the chance of severe diarrhea in people by 90% at 10 days after vaccination and by 80% at 3 months after vaccination. It is also not known how long protection lasts beyond 3 – 6 months after getting the vaccine.

• Cholera vaccines offer incomplete protection (except for Euvichol, only against O1 and not O139). Therefore, vaccination should never take the place of standard prevention and control measures.

Cholera - Laboratory Diagnosis

• Diagnosis of cholera is confirmed by stool culture (use of selective media is recommended) plus subsequent serogrouping/subtyping. Tests for V. cholerae are available in reference laboratories.

• Polymerase chain reaction (PCR) testing.

• Rapid dipstick testing for cholera is available for public health use in areas with limited access to laboratory testing, but specificity of this test is suboptimal so dipstick-positive specimens should be confirmed by culture if possible.

Shigellosis

• Shigellosis is a gastrointestinal infection caused by one of four species of Shigella bacteria:

  • S. sonnei: most common symptoms are diarrhea (sometimes bloody), abdominal pain, cramps, and fever. Nausea and/or vomiting, loss of appetite, headache, or malaise can also occur.

  • S. flexneri: causes diarrhea, abdominal pain, cramps, and fever but is often more severe than S. sonnei infection. Inflammation and ulceration of the lower part of the bowel (dysentery) is also common and illness can be prolonged and more severe. Complications of S. flexneri infection can include reactive arthritis (inflammation in response to infection in other part of body; can be accompanied by urethritis, conjunctivitis).

  • S. boydii: can cause diarrheal diseases of varying severity, but mostly are similar to those caused by S. sonnei.

  • S. dysenteriae: causes more severe disease than other forms of shigellae with higher death rates. Dysentery occurs in most cases, displaying itself as bloody stools. Complications caused by S. dysenteriae can include an enlarged colon due to toxins (toxic megacolon), haemolytic-uraemic syndrome (HUS)—which is a type of kidney failure, blood clots, and sepsis.

Shigellosis in Europe (ECDC)

• In 2019, in Europe 8308 cases of shigellosis were documented.

• Reference: https://atlas.ecdc.europa.eu/public/index.aspx?Dataset=27&HealthTopic=48

Shigellosis - Transmission, Symptoms, and Treatment

• Transmission: fecal-oral transmission through direct or indirect person-to-person contact is the main route. Stool typically remains infectious for 4 weeks after recovery. Convalescent and subclinical carrier status is observed in some persons. Contaminated food and beverages were also reported as a source of infection. Humans are the only natural reservoir for Shigella. Flies serve as vectors.

• Infectious dose: 10-100 organisms.

• All people are believed to be susceptible to some degree, but infants, elders, and the infirm are more likely to experience severe symptoms (significant dehydration and electrolyte loss with circulatory collapse and death).

• Incubation period: 1-3 days (range from 12 to 96h).

• Clinical symptoms: diarrhea, fever, nausea, toxemia, vomiting, cramps, stool with blood mucus and pus. Bacteremia is uncommon. Mild and asymptomatic infections can occur. Illness is usually self-limited, lasting an average of 4-8 days, in severe cases 3 to 6 weeks. Severe complications can include hemorrhagic colitis or HUS.

• Mortality rate: in some strains may be as high as 10-20%, but generally is quite low.

• An episode of shigellosis imparts serotype-specific immunity for at least several years. But patients may have additional episodes of shigellosis caused by other serotypes.

• Laboratory diagnosis: isolation (from stool).

• Treatment: of mild infection is supportive, mostly with rehydration; antibiotics (fluoroquinolone, azithromycin or a 3rd-generation cephalosporin) are given to moderate to severely ill and high-risk patients with bloody diarrhea or immunocompromise and may shorten the duration of illness and decrease contagiousness.

• Prophylaxis: no vaccine is currently available, but a live oral vaccine is being developed, and field trials in endemic areas are promising. Immunity is type specific so presumably the vaccine would need to be polyvalent or contain an antigen common to multiple serotypes. Prophylactic administration of antibiotics is not recommended.

• In a terrorist attack, Shigella would most likely be disseminated through the intentional contamination of food and water supplies.

STEC/VTEC infections

• In 2019, 7775 cases of Shiga toxin-producing E. coli (STEC) were reported.

• Reference: https://atlas.ecdc.europa.eu/public/index.aspx?Dataset=27&HealthTopic=48

Escherichia coli O157:H7

• Is one of 100 enterohemorrhagic serotypes of E. coli (the most frequently isolated EHEC); producer of Shiga toxins (the toxin is able to damage mucosal cells and vascular endothelial cells in the intestine wall, and renal vascular endothelia); cause of GI tract infections resulting in acute bloody diarrhea.

• Source: the strain is isolated from various domestic animals, mostly from cattle (it was obtained from the intestines of healthy animals, udder, milk; meat can be contaminated during slaughter).

• Route of infection: ingestion of raw or undercooked beef, raw vegetables, unpasteurized milk or juice, and contaminated water; easily transmitted from person-to-person (fecal-oral route); infectivity of stool is about one week after recovery in adults and up to 3 weeks in children.

• Infectious dose: 10-100 bacterial cells.

Escherichia coli O157:H7 - Symptoms and Diagnosis

• E. coli O157:H7 can cause severe hemorrhagic colitis characterized by severe abdominal pain and diarrhea (often grossly bloody); the illness is self-limited, lasts for an average of 8 days.

• A severe manifestation of the infection is hemolytic uremic syndrome (HUS; 5-10% of cases can develop HUS), which may lead to permanent kidney failure. The syndrome mainly occurs in children and elders. HUS causes a rapid fall in hematocrit and platelet count, elevated serum creatinine, hypertension, and possibly signs of fluid overload, bleeding diathesis (unusual susceptibility to bleed), and neurologic symptoms and signs.

• Mortality rate: overall is less than 1%; HUS cases 3-5%.

• Laboratory diagnosis: isolation (from stool; using sorbitol McConkey agar and immunoseparation technique, or isolation typical for any E. coli and serotypization); rapid stool assay for Shiga toxin or a test for the gene that encodes the toxin.

Escherichia coli O157:H7 - Treatment and Prophylaxis

• Treatment: mainly fluid and electrolyte replacement. Antibiotics have not been shown to alleviate symptoms, reduce carriage of the organism, or prevent hemolytic-uremic syndrome. Fluoroquinolones are suspected of increasing release of enterotoxins and the risk of HUS. Antidiarrheal agents, such as loperamide (imodium), should also be avoided as they may prolong the duration of the infection.

• Prophylaxis: no vaccine available.

• In a terrorist attack, the microorganism would most likely occur due to intentional contamination of food and water supplies; aerosolisation could be a possibility.

Salmonellosis in Europe (ECDC)

• In 2019, salmonellosis was one of the most commonly reported gastrointestinal infections in humans in the EU (87924 cases reported).

• Reference: https://atlas.ecdc.europa.eu/public/index.aspx?Dataset=27&HealthTopic=48

Salmonellosis

• Bacteria of the genus Salmonella cause diarrheal illness, sometimes septicemia; some serotypes are responsible for many of the foodborne gastrointestinal illnesses of man and animals, the others for typhoid fever in humans.

• For more detailed description the infection in humans visit: https://www.msdmanuals.com/professional/infectious-diseases/gram-negative-bacilli/overview-of-salmonella-infections

• Routes of exposure: oral – consumption of contaminated food and water; fecal-oral route is the most common mode of person-to-person transmission.

• Infective dose is unknown; infectivity of the bacterium is moderate; a carrier state occurs and it may persist for months and years.

• Incubation period: 6 to 72 hours.

• Clinical manifestation: gastroenteritis (nausea, vomiting, abdominal cramps, diarrhea, weakness, chills, fever); typhoid syndrome (high spiking fever, abdominal cramps, diarrhea, septicemia, enlarged spleen, occasional meningeal signs); mortality rate is lower than 1% for most serotypes.

• Laboratory diagnosis: isolation (stool, blood, suspected food).

Salmonellosis - Treatment and Prophylaxis

• Treatment:

  • Gastroenteritis - rehydration; ciprofloxacin, azithromycin, ceftriaxone, or trimethoprim/sulfamethoxazole only for high-risk patients and patients with systemic or focal infections. Antibiotics do not hasten resolution of gastroenteritis, may prolong excretion of the organism, and are unwarranted in uncomplicated cases. However, in older nursing home residents, infants, and patients with hemoglobinopathies, HIV infection, or other immunocompromising conditions, increased mortality dictates treatment with antibiotics.

  • Typhoid fever – ceftriaxone, fluoroquinolone, or azithromycin for 14 days. Antibiotic resistance is common and increasing, particularly in endemic areas, so susceptibility testing should be performed. Carriers should be given antibiotics. The cure rate is about 80% with amoxicillin, TMP/SMX, or ciprofloxacin given for 4 to 6 weeks.

• Prophylaxis: a typhoid vaccine is available (a live-attenuated oral, containing Ty21a strain), about 70% effective, recommended for travelers, people living in typhoid-endemic areas, persons who have continued household contact with carriers, laboratory workers.

Salmonella as a Biological Weapon

• In a terrorist attack, salmonellosis would most likely occur due to intentional contamination of food or water supplies.

• The 1984, Rajneeshee bioterror attack in the Dalles (Oregon, United States) was the food poisoning due to the deliberate contamination of salad bars at ten local restaurants with Salmonella (S. Typhimurium). A leading group of followers of Bhagwan Shree Rajneesh (later known as Osho) had hoped to incapacitate the voting population of the city so that their own candidates would win the 1984 Wasco County elections.

• The attack resulted with 751 cases (45 persons were hospitalized, no fatalities).

• The outbreak cost local restaurants hundreds of thousands of dollars and health officials shut down the salad bars of the affected establishments.