1. TASHKENT MEDICAL ACADEMY
Infectious and children infectious diseases department
Theme: Early and Comparative diagnosis of diseases with the syndrome of diarrhea
Lecturer:

2. Definition
Bacillary dysentery is a type of dysentery caused by Shigellosis. Bacillary dysentery is associated with species of bacteria from the Enterobacteriaceae family. The term is usually restricted to Shigella infections. Shigellosis is caused by one of several types of Shigella bacteria. Three species are associated with bacillary dysentery : Shigella sonnei, Shigella flexneri and Shigella dysenteriae. One study in China indicated that Shigella flexneri was the most common serotype. Salmonellosis caused by Salmonella enterica (serovar Typhimurium) has also been described as a cause of bacillary dysentery, though this definition is less common. It is sometimes listed as an explicit differential diagnosis of bacillary dysentery, as opposed to a cause. Bacillary dysentery should not be confused with diarrhea caused by a bacterial infection. One characteristic of bacillary dysentery is blood in stool which is the result of invasion of the mucosa by the pathogen.

3. Synonyms
Shigella
Shigella infection
Salmonella infection

4. Morphological Description of Biologic Agent
Shigella is a genus of gram-negative, non-spore forming rod-shaped bacteria closely related to Escherichia Coli and Salmonella. The causative agent of human shigellosis, Shigella cause disease in primates, but not in other mammals. It is only naturally found in humans and apes. During infection, it typically causes dysentery.

5. Mode of Transmission
Shigella infection is typically via ingestion (fecal–oral contamination); depending on age and condition of the host as few as ten bacterial cells can be enough to cause an infection.

6. Signs and Symptoms
Most people who are infected with Shigella develop diarrhea, fever, and abdominal cramps.  Severity of the disease ranges from mild to very severe diarrhea.  Diarrhea is bloody percent of the time and most often contains mucus. Rectal spasms are common.  The illness starts 12 hours to 6 days, usually 1-2 days, after exposure.  Dehydration is also a common symptom of Shigella infection. Nausea or vomiting may also be experienced. Muscle aches also occur. In some cases, white blood cell count is lower than normal at the onset.

7. Diagnostics/Lab Tests
Your own observation of symptoms.
Medical history and physical exam by a doctor.
Laboratory stool culture.
Blood counts.

8. Period of Communicability
Shigellosis is spread during the acute infection and until the infectious agent is no longer present in feces. This can last as long as four weeks. Asymptomatic carriers have the ability to transmit disease. The duration of carriage may be reduced with the use of antibiotics.

9. Incubation Period
The incubation period may range from 12 to 96 hours (one to three days).

10. Outcome of Disease
Most shigella infections are mild and don't require drastic treatment. However, in a severe attack, excessive dehydration can be fatal (especially in infants and young children) if treatment is unsuccessful.

11. Treatment
Fluids and electrolyte replacement if excessive fluid loss through diarrhea or vomiting.
Agents are not recommended as they may prolong the course of disease.
Treatment is recommended for most symptomatic patients. Use of antibiotics will shorten the period of fecal excretion of the infecting strain and will shorten the clinical course of disease often to a few days.
Antibiotics
- for adults and children, if the strain is susceptible, are ciprofloxacin or TMP/SMX or azithromycin.
Antibiotic resistance frequently develops after treatment.

12. Control Measures Good personal hygiene Toilet hygiene
Wash soiled clothing and bed linen
Handling food
While you are suffering from diarrhea you should not go to work/school.
Sanitation of food utensils

13. General Characteristics of Salmonella
Coliform bacilli (enteric rods)
Motile gram-negative facultative anaerobes
Non-lactose fermenting
Resistant to bile salts
H2S producing

14. Classification and Taxonomy of Salmonella (Confused)
Old: Serotyping & biochemical assays used to name individual species within genus (e.g., Salmonella enteritidis, S. choleraesuis, S. typhi)
Over 2400 O-serotypes (referred to as species) (Kauffman-White antigenic schema)
Bioserotyping (e.g., S. typhimurium)
New: DNA homology shows only two species Salmonella enterica (six subspecies) and S. bongori
Most pathogens in S. enterica ssp. enterica

15. Epidemiology of Salmonella Infection

16. Annual Reported Incidence of Salmonella Infection (excluding typhoid fever)

17. Clinical Syndromes of Salmonella
Salmonellosis = Generic term for disease
Clinical Syndromes
Enteritis (acute gastroenteritis)
Enteric fever (prototype is typhoid fever and less severe paratyphoid fever)
Septicemia (particularly S. choleraesuis, S. typhi, and S. paratyphi)
Asymptomatic carriage (gall bladder is the reservoir for Salmonella typhi)

18. Epidemiology and Clinical Syndromes of Salmonella (cont.)
Enteritis
Most common form of salmonellosis with major foodborne outbreaks and sporadic disease
High infectious dose (108 CFU)
Poultry, eggs, etc. are sources of infection
6-48h incubation period
Nausea, vomiting, nonbloody diarrhea, fever, cramps, myalgia and headache common
S. enteritidis bioserotypes (e.g., S. typhimurium)

19. Pathogenesis of Salmonella
Enteritis (cont.)
Virulence attributable to:
Invasiveness
Intracellular survival & multiplication
Endotoxin
Exotoxins: Effects in host have not been identified
Several Salmonella serotypes produce enterotoxins similar to both the heat-labile (LT) and heat-stable enterotoxins (ST), but their effect has not been identified
A distinct cytotoxin is also produced and may be involved in invasion and cell destruction

20. Pathogenesis of Salmonella (cont.)
Invasiveness in Enteritis (cont.)
Penetrate mucus, adhere to and invade into epithelial layer (enterocytes) of terminal small intestine and further into subepithelial tissue
Bacterial cells are internalized in endocytic vacuoles (intracellular) and the organisms multiply
PMN’s confine infection to gastrointestinal (GI) tract, but organisms may spread hematogenously (through blood, i.e., septicemia) to other body sites
Inflammatory response mediates release of prostaglandins, stimulating cAMP and active fluid secretion with loose diarrheal stools; epithelial destruction occurs during late stage of disease

21. Clinical Progression of Salmonella Enteritis
Lamina propria = thin membrane between epithelium & basement layer
Hyperplasia = abnormal increase in # of normal cells
Hypertrophy = abnormal increase in normal tissue/organ size
Prostaglandins = potent mediators of diverse set of physiologic processes

22. Epidemiology & Clinical Syndromes (cont.)
Enteric Fevers
S. typhi causes typhoid fever S. paratyphi A, B (S. schottmuelleri) and C (S. hirschfeldii) cause milder form of enteric fever
Infectious dose = 106 CFU
Fecal-oral route of transmission
Person-to-person spread by chronic carrier
Fecally-contaminated food or water
10-14 day incubation period
Initially signs of sepsis/bacteremia with sustained fever (delirium) for > one week before abdominal pain and gastrointestinal symptoms

23. Pathogenesis of Salmonella (cont.) Enteric Fevers (cont.)
Virulence attributable to:
Invasiveness
Pass through intestinal epithelial cells in ileocecal region, infect the regional lymphatic system, invade the bloodstream, and infect other parts of the reticuloendothelial system
Organisms are phagocytosed by macrophages and monocytes, but survive, multiply and are transported to the liver, spleen, and bone marrow where they continue to replicate
Second week: organisms reenter bloodstream and cause prolonged bacteremia; biliary tree and other organs are infected; gradually increasing sustained fever likely from endotoxemia
Second to third week: bacteria colonize gallbladder, reinfect intestinal tract with diarrheal symptoms and possible necrosis of the Peyer’s patches

24. Clinical Progression of Enteric Fever (Typhoid fever)
Liver, spleen, bone marrow
(10-14 days)
(RES)
Gastrointestinal Symptoms
Clinical Progression of Enteric Fever (Typhoid fever)
Lumen (intraluminal); ileocecal area = see above - Anatomy of Digestive Tract
RES = sum total of strongly phagocytic cells; primarily found in lymph nodes, blood, liver, spleen and bone marrow
Hyperplastic changes = see hyperplasia above - Clinical Progression of Enteritis

25. Microbial Defenses Against Host Immunological Clearance
ENCAPSULATION and
ANTIGENIC MIMICRY, MASKING or SHIFT
CAPSULE, GLYCOCALYX or SLIME LAYER
Polysachharide capsules Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, etc.
Polypeptide capsule of Bacillus anthracis
EVASION or INCAPACITATION of PHAGOCYTOSIS and/or IMMUNE CLEARANCE
PHAGOCYTOSIS INHIBITORS: mechanisms enabling an invading microorganism to resist being engulfed, ingested, and or lysed by phagocytes/ phagolysosomes
RESISTANCE to HUMORAL FACTORS
RESISTANCE to CELLULAR FACTORS
See Chpt. 19

26. Methods That Circumvent Phagocytic Killing
, Salmonella typhi
See Chpt. 19

27. Epidemiology & Clinical Syndromes (cont.)
Septicemia
Can be caused by all species, but more commonly associated with S. choleraesuis, S. paratyphi, S. typhi, and S. dublin
Old, young and immunocompromised (e.g., AIDS patients) at increased risk

28. Gall bladder usually the reservoir
Epidemiology & Clinical Syndromes (cont.)
Asymptomatic Carriage
Chronic carriage in 1-5% of cases following S. typhi or S. paratyphi infection
Gall bladder usually the reservoir
Chronic carriage with other Salmonella spp. occurs in <<1% of cases and does not play a role in human disease transmission

29. Treatment, Prevention and Control of Salmonella Infections
Enteritis:
Antibiotics not recommended for enteritis because prolong duration
Control by proper preparation of poultry & eggs
Enteric fever:
Antibiotics to avoid carrier state
Identify & treat carriers of S. typhi & S. paratyphi
Vaccination can reduce risk of disease for travellers in endemic areas

30. Botulism Organism History Epidemiology Transmission Disease in Humans
Disease in Animals
Prevention and Control
In today’s presentation we will cover information regarding the organism that causes botulism and its epidemiology. We will also talk about the history of the disease, how it is transmitted, species that it affects, including humans, and the clinical and necropsy signs observed. Finally, we will address prevention and control measures for botulism.

31. Organism Clostridium botulinum Gram positive
Obligate anaerobic bacillus
Spores
Ubiquitous
Resistant to heat, light, drying and radiation
Specific conditions for germination
Anaerobic conditions
Warmth (10-50oC)
Mild alkalinity
Botulism is caused by the bacterium Clostridium botulinum. It is a gram positive, spore-forming, obligate anaerobic bacillus. The clostridial spores are ubiquitous in soil and are very resistant to heat, light, drying and radiation. Spores may survive boiling for several hours at 100 oC, however exposure to moist heat at 120 oC for 30 minutes will kill the spores. Specific conditions are required for the germination of spores. These include anaerobic conditions (such as rotting carcasses or canned food), warmth, and mild alkalinity. The photo shows the bacillus shape of the bacterium C. botulinum. (Source: CDC Public Health Image Library:

32. Neurotoxins Seven different types: A through G
Different types affect different species
All cause flaccid paralysis
Only a few nanograms can cause illness
Binds neuromuscular junctions
Toxin: Destroyed by boiling
Spores: Higher temperatures to be inactivated
After germination, clostridial spores release neurotoxins. There are 7 antigenic types of neurotoxins, classified as A through G. Typically, different neurotoxin types affect different species. Only a few nanograms of these toxins can cause severe illness. All cause flaccid paralysis in the species affected. Toxin is produced in improperly processed, canned, low-acid or alkaline foods, and in pasteurized and lightly cured foods held without refrigeration, especially in airtight packaging. The physiologic mechanism of the neurotoxin is to irreversibly bind at neuromuscular junctions to prevent the release of acetylcholine (Ach). This causes muscular paralysis. The peripheral sensory nerves and the central nervous system are usually not affected. The toxin can be destroyed heat and cooking food at 80oC for 30 minutes, however, inactivation of spores requires a much higher temperature.

33. Neurotoxins Neurotoxin A B C D E F G Human X Horses Cattle Sheep Dogs
Avian
Mink & Ferret
This table summarizes the most common neurotoxin type affecting the various species affected by C. botulinum. All types of botulinum toxins produce the same clinical signs; however, the toxin type is important if antiserum is used for treatment. Type G has been isolated from soil and autopsy specimens but an etiologic role has not been established. Type E outbreaks are usually related to fish, seafood and meat from marine mammals.

34. History 1793, Justinius Kerner “Botulus” = Latin for sausage
“Wurstgift”
“Botulus” = Latin for sausage
1895, Emile von Ermengem
Isolated organism during Belgium outbreak
U.S. outbreaks led to improved industry processing
Botulism was first discovered by the German physician, Justinius Kerner in He called the substance “wurstgift” since he found it in spoiled sausages. During this period of time, sausage was made by filling a pig’s stomach with meat and blood, boiling it in water then storing it at room temperature. These were ideal conditions for clostridial spores to survive. Botulism gets it name from “botulus” which is Latin for sausage. In 1895, Emile von Ermengem identified Clostridium botulinum as the actual source of a botulism outbreak in Belgium. Several outbreaks of botulism in the US have led to federal regulations for food preservation. In 1919, an outbreak from canned olives (15 deaths) led to the use of high temperatures as industry standards for preserving foods. In 1973, an outbreak from canned soup led to further regulations for the safe processing of canned foods.

35. Transmission Ingestion Wound contamination Inhalation
Organism
Spores
Neurotoxin
Wound contamination
Inhalation
Person-to-person not documented
Botulism transmission typically occurs through ingestion of the organism, neurotoxin or spores. If the organism is ingested, it then incubates in the stomach and produce spores which then germinate to release neurotoxin. If spores are ingested, germination follows and neurotoxin is released. Finally if spores have germinated within contaminated food, the neurotoxin itself is ingested, causing rapid progression of the disease. Other forms of transmission involve contamination of open wounds with clostridial spores. Additionally, inhalation of the neurotoxin is also possible. This is the most likely bioterrorism method that would be used for this agent. No instance of secondary person-to-person transmission has been documented.

36. Epidemiology In U.S., average 110 cases each year Case-fatality rate
Approximately 25% food-borne
Approximately 72% infant form
Remainder wound form
Case-fatality rate
5-10%
Infective dose- few nanograms
In the US, there are on average 110 cases of botulism per year. Typically about 25% are food-borne related illnesses. Approximately 72% are the infant botulism form and the remainder are wound related. In 1995, the reported case-fatality rate for botulism cases was 5-10%.

37. Epidemiology 1977, Largest botulism outbreak Alaska
Michigan - 59 people
Poorly preserved jalapeno peppers
Alaska
27% of U.S. foodborne botulism cases
226 cases from 114 outbreaks
To date, the largest botulism outbreak in the US occurred in 1977 in Michigan. Fifty-nine people were affected after eating poorly preserved jalapeno peppers. Approximately 27% of U.S. food-borne botulism cases occur in Alaska. During , Alaska recorded 226 cases of food-borne botulism from 114 outbreaks. All were Alaska Natives and were associated with eating fermented foods, which is a part of their culture. Due to changes in the fermentation process (use of closed storage containers), an increase in botulism rates occurred in Alaska from

38. Human Disease Three forms All forms fatal and a medical emergency
Foodborne
Wound
Infant
All forms fatal and a medical emergency
Incubation period: hours
Human botulism illness can occur in three forms: foodborne illness, infant botulism and wound contamination. These forms vary by how the toxin is obtained. All forms of the disease can be fatal and should be considered a medical emergency. The incubation period can range from 6 hours to 2 weeks. However, signs typically occur hours after toxin release. Humans can be affected by types A, B, E and rarely F neurotoxins.

39. Foodborne Botulism Preformed toxin ingested from contaminated food
Most common from home-canned foods
Asparagus, green beans, beets, corn, baked potatoes, garlic, chile peppers, tomatoes; type A
Improperly fermented fish (Alaska); type E
Foodborne botulism occurs when the preformed neurotoxin is ingested. The most common source of the preformed toxin is contaminated food, usually from improperly home-canned vegetables or fermented fish. Fifty percent of food-borne outbreaks in the US are caused by type A toxins. The most commonly isolated neurotoxin is type A for canned foods and type E for improperly fermented fish products.

40. Infant Botulism Most common form in U.S. Spore ingestion
Germinate then toxin released and colonize large intestine
Infants < 1 year old
94% < 6 months old
Spores from varied sources
Honey, food, dust, corn syrup
The most common form of human botulism occurs in infants. Annual incidence in the US is two cases per 100,000 live births. Spores are ingested, germinate, then release their toxin and colonize the large intestine. It occurs predominantly in infants less than 1 year old (94% are less than 6 months old). The spores are obtained from various sources such as honey, food, dust, and corn syrup.

41. Wound Botulism Organism enters wound
Develops under anaerobic conditions
From ground-in dirt or gravel
It does not penetrate intact skin
Associated with addicts of black-tar heroin
Wound botulism is rare and occurs when the organism gets into an open wound and develops under anaerobic conditions. The organism typically comes from ground-in dirt or gravel. C. botulinum, its spores or neurotoxin cannot penetrate intact skin. This form has also been associated with addicts of black-tar heroin. It is thought to be contaminated with dirt or boot polish during its preparation process. There have been clusters of cases each year in these drug users, some resulting in fatalities.

42. Adult Clinical Signs Nausea, vomiting, diarrhea Double vision
Difficulty speaking or swallowing
Descending weakness or paralysis
Shoulders to arms to thighs to calves
Symmetrical flaccid paralysis
Respiratory muscle paralysis
In humans, the clinical signs of botulism are similar for all forms of the disease. Gastrointestinal signs (i.e., nausea, vomiting, diarrhea) are usually the first signs to appear. They are followed acutely by neurological signs, such as bilateral cranial nerve deficits. The victim will have double vision, and difficulty seeing, speaking and swallowing. This soon develops into a descending weakness to symmetrical flaccid paralysis. This paralysis can affect the respiratory muscles and lead to death.

43. Infant Clinical Signs Constipation Lethargy Poor feeding Weak cry
Bulbar palsies
Failure to thrive
Children less than 1 year of age with the following clinical signs should be suspected of infant botulism. Constipation, lethargy, poor feeding, weak cry, bulbar palsies, failure to thrive, and progressive weakness. This can lead to impaired respiration and sometimes death if not treated promptly. The child in this picture is too weak to hold up its head as noted by the limp appearance of the neck and arms. It was an infant case of botulism. 72% of natural botulism cases occur in children under 1 year of age. California Department of Health Services

44. Diagnosis Clinical signs
Toxin in serum, stool, gastric aspirate, suspected food
Culture of stool or gastric aspirate
Takes 5-7 days
Electromyography also diagnostic
Mouse neutralization test
Results in 48 hours
Clinical signs can provide a tentative diagnosis for botulism intoxication. The definitive diagnosis in humans involves identifying the toxin in serum, stool, gastric aspirate, or if available, the suspected food. Feces are usually the most reliable clinical sample in foodborne or infant botulism. Additionally, cultures of stool or gastric aspirate samples may produce the organism, but can take 5-7 days. Electromyography (EMG) can also be diagnostic. The most widely used and sensitive test for detecting botulism toxin is the mouse neutralization test. Serum or stool with the suspected botulism organism is injected into a mouse and observed for clinical signs of the disease. Results are available in 48 hours.

45. Treatment Intensive care immediately Botulinum antitoxin
Ventilator for respiratory failure
Botulinum antitoxin
Derived from equine source
CDC distributes
Used on a case-by-case basis
Botulism immune globulin
Infant cases of types A and G
Most cases of botulism require immediate intensive care treatment. Due to respiratory paralysis, a mechanical ventilator will be needed if respiratory failure occurs. An intravenous equine-derived botulinum antitoxin is available on a case-by-case basis from the CDC through state and local health departments. Botulism immune globulin was approved for use on October 23, 2003 for the treatment of infant botulism caused by types A and G.