1. Invasive Enteritis and Systemic Infections

2. Some bacteria are able to enter the blood stream and cause systemic diseases from the intestine:
Salmonella spp.
Brucella spp.
Listeria monocytogenes.

3. Salmonella species

4. Specie: S. enterica ≈ 200 serotypes.
Genus: Salmonella.
Specie: S. enterica ≈ 200 serotypes.
The main antigens that distinguish salmonella serovars are:
The capsular Vi antigen.
The somatic O antigen (LPS).
The flagellar H antigen.
Common serovars:
S. Enteriditis→ gastroenteritis.
S. Typhimurium → gastroenteritis, osteomyelitis in sickle cell disease.
S. Typhi & S. Paratyphi A, B and C → Typhoid fever + carrier state. N
Chronic carrier: when excrete salmonella for a year or more. Can occur with any serotype but much more common with S. Typhi then S. Paratyphi.
The bacilli are present in the gall bladder or the urinary tract.

5. Typhoid fever (typhus like fever)
Caused By:
S. enterica serovar Typhi
S. enterica serovar Paratyphi A, B& C.
Reservoir: Human only; no animal reservoirs.
Transmission:
Fecal- oral route from human patients and carriers (Typhoid Mary).
Contaminated water or food.
Pathogenic dose:
CFU/ml in normal persons (less in patients with hypochlorhydria). N

6. Pathogenesis:
Incubation period: 5 to 21 days.
Escape the stomach, and reach the ileocecal region.
Invade the microfold cells (M cells) in the ileum mucosa by endocytosis and pass to lamina propria → engulfed by the macrophages and dendritic cells Due to the anti-phagocytic capsule (Vi antigen) they will survive in the macrophages → carried to the mesenteric lymph nodes, then to the blood→ primary transient bacteremia.
Multiply in the RES (macrophages of the liver and spleen), and bone marrow → secondary sustained bacteremia.

7. Secondary bacteremia leads to invasion of:
Kidney; nephritis→ bacteria present in the urine → chronic carriers (stones or schistosoma).
Gallbladder: cholecystitis and chronic carrier state in gall stones.
Reinvasion of small intestine: (through the bile & blood); inflammation & ulceration of Peyer’s patches (immune-mediated destruction) → hemorrhages and perforation.
Symptoms & signs: fever that continue for 4 to 8 weeks in untreated cases (stepladder fever), relative bradycardia, hepatosplenomegaly, 25% have rose spots (trunk & abdomen) in the first week.
Prognosis: mortality rate without treatment ≈ 20%. n

8. Rose spots

9. Diagnosis: Direct microbial detection or indirect by serology.
Clinical specimens: Blood, bone marrow aspiration, stool, urine or rose spot.
In the 1st week: positive bone marrow culture in 95%, positive blood culture in 80% of patients In the 3rd week: positive stool culture in 85%.
Direct detection (blood &BM culture): ml cultivated in blood culture bottle for 7 days.
Growth indicators: turbidity, hemolysis, and air bubbles Subculture on XLD media: non-lactose fermenter, H2S producers Identification: biochemical or serological tests. Serotyping by salmonella polyvalent & mono valent reagent.

10. N

11. Indirect: Serology: Widal test:
Detection of anti-salmonella antibodies in the serum.
Antibodies against:
O antigen of S. Typhi, S. Paratyphi A, B & C.
H antigen of S. Typhi and S. Paratyphi A, B & C.
Significant titer: 1/160 or more.
Four fold rising titer or seroconversion.
Treatment: start with injectable ciprofloxacin or third geberation cephalosporin then sheft according to sensetivty results.
Chronic carriers: ciprofloxacin and cholecystoctomy in the case of failiure.
Vaccination: Injectable: killed vaccine or capsular Vi antigens Oral vaccine: live attenuated. N

13. Brucellosis (undulant fever) (Malta fever )

14. Causative agent: Genus Brucella (Zoonosis).
Brucella abortus: cattle.
Brucella melitensis: camels and goats.
Microbiology:
Small gram negative coccobacilli. Non-capsulated, non-motile.
Transmission:
Ingestion of unpasteurized milk or milk products.
Direct contact with infected animal.
Inhalation of contaminated dust & aerosols (laboratory acquired).
Incubation period: 5 days to several months.

15. Attach to intestinal microvilli.
Pathogenesis:.
Attach to intestinal microvilli.
Engulfed by intestinal macrophage → survive inside the macrophages → carried to the lymph nodes and the RES→ mild inflammation (low virulence) → establish chronic granulomatous lesions if not or inadequately treated.
Symptoms of brucellosis:
- Acute septicemia: undulating fever, night sweat, headache, joints pain, anorexia, weight loss &depression.
-Chronic: symptoms for ≥ a year with localized infection (spondylitis, osteomyelitis, tissue abscesses, or uveitis).
- It cause abortion and miscarriages in pregnant ladies A cause of fever of unknown origin (PUO). N

16. Specimens: bone marrow aspiration, blood, liver biopsy and serum.
Diagnosis:
Specimens: bone marrow aspiration, blood, liver biopsy and serum.
Direct: culture: biphasic (solid and liquid) Castaneda media (7-21 days incubation) or automated system (3 days).
Indirect: Serology:
Agglutination brucella test, Rose Bengal agglutination or ELISA Significant titer: 1/80 in non-endemic countries 1/160 in endemic countries False negative reactions due to prozone phenomena.
Treatment: multiple antibiotics for 6 weeks. N

17. N

18. Listeria monocytogenes

19. Listeria monocytogenes: gram positive, motile bacilli
Listeria monocytogenes: gram positive, motile bacilli. Grow well at 4-8o C.
Associated food and Transmission: Unpasteurized milk products, ready-to-eat meat, undercooked meat, fresh chees & raw vegetables.
Incubation period: days.
Pathogenesis:
- Invasion of intestinal epithelia.
- Intracellular survival, production of listeriolysin-O, actin polymerization and spreading from cell to cell (febrile gastroenteritis in immunocompetent)→ evade the immune response→ bacteremia in pregnant women, neonates, immunosuppressed and old patients.
- Predilection to placenta and CNS of infants.

20. listeriolysin

21. Symptoms:
Immunocompetent (rare): fever, watery diarrhea, vomiting.
Immunocompromised: septic shock and/or meningoencephalitis.
Infection in pregnancy: Fever, chills, and back pain→ fetal death, premature birth, or infected newborns.
Infected infants: granulomatosis infantiseptica: abscesses and/or granulomas in the liver, spleen, lungs and brain. Most neonates are stillborn or die soon after birth.
Diagnosis: CSF or blood culture.
Treatment: penicillin or trimethoprim- sulfamethoxazole.

22. Boil it, cook it, peel it, or forget it