Micro Lecture 16; Enteric meningitis

Diarrhea

loose, watery, stools more than 3x in one day which might be associated with cramps bloating, nausea, and urgent need to have a bowel movement

Bristol stool chart Type 6 and 7

6: Fluffy pieces with ragged edges, a mushy stool

7: watery, no solid pieces, entirely liquid

Acute Diarrhea

Bacterial, parasitic infection, viral or food intolerance

Chronic Diarrhea

Associated with functional disorders, eg. irritable bowel syndrome (IBS)

Osmotic

Diarrhea that has too much water is drawn into the bowels. Due to malabsorption (esp, if your lactose intolerance) or laxative overuse.

Secretory (watery)

Diarrhea that has active secretion of fluid from plasma into bowel. Diarrhea has ion composition of plasma and continues even when fasting. Often caused by bacterial toxins (eg. cholera, ETEC) . (Most dangerous ones end up secreting plasma)

Exudative

presence of blood and pus in the stool. Happens with inflammatory bowel diseases like Crohn’s disease or ulcerative colitis and several infections.

• - Dysentery is bloody diarrhea, blood is caused by invasion bowel tissue by pathogen (eg. EHEC, salmonella, shigella, entamoeba histological, and others)

Enteric Gram Negative Bacteria

goes from enteric to intestinal

• - Rod shaped Gram negative bacteria

• - most are commensals or pathogens in intestines of humans and other humans

How many common gram negative enteric are there and what is there names?

there are 7 common gram-neg enteric, all are rods (bacilli) except Vibrio which is a short helically shaped rod. All are motile except Klebsiella and shigella.

• -Escherichia coli

• - Klebsiella pneumoniae

• -Salmonella dystenteriae

• - Vibris cholera

• -Campylobacter jejuni

• - Helicobacter Pylori

In Enteric, which are classified as Enterobacteriaceae?

Escherichia coli, Klebsiella pneumoniae (<—-- these are also coliform/commensals), salmonella typhi, and shigella dysenteriae

• - family of gram-negative bacilli that contains more than 100 species of bacteria which inhibit the intestines of humans and animals.

Which enteric fall under the Vibrionaceae family?

Vibrio cholera

Which enteric do not have a family assigned?

Campylobacter Jejuni and Helicobacter pylori

Enterobacteriaceae

• - Transmission is fecal-oral

• - In the US happens mostly through mass processing of food, cruise ships, meat packing plants, restaurant chains, etc.

• - outbreaks are monitored by the CDC

• -Source needs to be identified and recall of contaminated product issue

• - In third world countries: poor quality of water supply—→ much more incidence

Helicobacter pylori

is a spirochete which inhibits the stomach

Characteristics of Gram-neg Enteric

• - Endotoxin: part of lipopolysaccharide found in all Gram-negative bacteria (the lipid A part)

• - Catalase-positive

• - surface antigens (useful in stereology, can determine virulence): H antigen (flagella), K antigen (capsule or fimbriae), O antigen (LPS, carbohydrate part)

• - R factors (antibiotic resistance and virulence)

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What are enteric bacteria good at?

very efficient in exchanging genetic material by either conjugation or transduction by phage.

• - coliforms grow as dark colonies on EMB agar

Escherichia Coli

named for Escherich (Germany) and inhibiting the colon

• - Coliform

• - Normal microflora of 100% of human colon and live in the intestine of all warm-blooded animals

• -special strains are highly virulent due to possession of virulence factors

• -pathology:virulent strains of E.coli can cause

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Gastroenteritis

Diarrheal type of diseases which are transmitted by fecal oral routes are caused by fecal oral routes are caused by several strains of E.coli, each having unique virulence factors.

Infants are most impacted by

E.coli is a major cause of neonatal meningitis, caused by strains which have the K1 capsule, quick diagnosis and treatment is important. Also, Strep ag alactiae (GRP B strep)

UTI

urethritic, cystitis caused by E.coli as well

Enterotoxigenic E coli (ETEC)

strains that produce a plasmid-encoded heat stable toxin which causes watery diarrhea. Toxin stimulates hypersecretion of fluids and electrolytes from the gut epithelial cells. Significant cause infant death (especially in 3rd world).

• -common cause of traveler’s diarrhea

Enterohemorrhagic E coli (EHEC)

plasmid encoded toxin causes bloody diarrhea (dysentery). Toxin disrupts protein synthesis causing destruction of intestinal microvilli. Strain E. coli O157:H7 is a major cause of food-associated diarrheal disease in US.

Hemolytic uremic syndrome (HUS)

complication of EHEC infection 5%-10% of children younger than 10 years of age. Characterized by hemolytic anemia and damage to the kidneys (leading to kidney failure).

• -Antibiotic treatment contraindicated (worsens HUS)

UTI and Cystitis

contamination of urethra by bacteria that reside in the colon. Bacterial ascend causing inflammation of bladder (cystitis) caused by certain strains of E.coli (uropathogenic strains, UPEC) that produce extra adhesion (fimbriae or pilli) that bind to cell lining of bladder. The infection could further ascend to kidneys (pyelonephritis) and the prostate (prostatitis)

Salmonella Typhi

• - Member of the Enterobacteriaceae family

• - Gram negative, short bacillus

• - Peritrichous flagella, highly motile

• - Causes typhoid fever (or enteric fever)

• - Transmission: fecal-oral; asymptomatic carriage is possible (Typhoid Mary)

Typhoid fever or Enter

Bacteria are ingested by food/water contaminated with feces from an infected person. Bacteria multiply in the blood stream and are observed into the digestive tract and eliminated with the waste.

• - Mostly third world countries, in the USA the majority of cases happens in travelers from other countries.

• - Prevention: A vaccine is available but is generally used for people that travel to countries where exposure might happen. Strict attention to food and water precautions while traveling to countries is the most effective preventative method.

symptoms for typhoid fever or enteric fever

sustained fever as high as 40* C (104F) with perfuses sweating. Gastroenteritis and diarrhea. Rash or flat, rose-colored spots (petechiae) may appear.

Salmonellosis

infection with different (less virulent) species of Salmonella these are S enteritidis and S. typhimurium, there are over 400 strains in these groups

• - Transmission: both humans and animals

• - Zoonosis: Fecal-oral transmission from animal to human. Usually in contaminated food.

• - Undercooked animal products like poultry, ground beef (most common)

• - Fruit and vegetable contaminated with manure (mulch)

• - Human to human transmission rare —→ due to poor personal hygiene

Salmonella gastroenteritis

most common form of Salmonellosis. Oral ingestion is followed by colonization of lower intestine

• - Bacteria are capable of mucosal invasion which results in mucosal inflammation, leading to diarrhea, fever, cramps. Illness usually lasts 3-7 days, most people recover without medical treatment

• - Less common now due to improved hygiene regulations and vaccination of laying hens

Shigella dysenteries

• -non-motile

• - Gram-negative.

• - Enterobacteriaceae family member

• - Produces diarrhea-inducing enterotoxin

Shigellosis

shigella is frequently found in water polluted with human feces. Associated with poor personal hygiene, and ineffective water treatment. Transmitted through fecal-oral route. Human is the only reservoir for this bacterium. Few bacteria required for infection (resistant to stomach acid) person to person spread is possible, particularly with small children in daycare situations; homosexual men also at risk.

• - Onset time is 12-50 hours

• -Treatment: Usually self-limiting; fluid and electrolytes replacement suggested. Antibiotic treatment can shorten symptoms and fecal shedding. Vaccine is in development and shows promise

symptoms of shigellosis

may range from mild abdominal discomfort to full blown bloody diarrhea (bacillary dysentery). Cramps, diarrhea, fever, vomiting, blood, pus and mucus

Vibrio Cholerae

-Gram negative

-highly motile curved rod

-Endemicin Africa and South Africa

• - Virulence: Fecal-oral transmission. Once ingested, Vibrio colonizes the GI tract. Adheres to microvilli by means of fimbriae. Releases Cholera toxin which causes symptoms of cholera

• -Pathology: toxin stimulates hypersecretion of fluids and electrolytes from the gut epithelial cells into lumen of intestines, results in severe dehydration and death due to hypovolemic shock

• - Therapy: replacement of lost fluids and electrolytes by IV infusion or orally, measure amount of fluid excreted and replaced

Symptoms of Vibrio Cholerae

secretory diarrhea with massive fluid and electrolyte efflux (characteristics of rice water stool). Leads to severe dehydration.

Campylobacter jejuni

• - Motile

• - gram negative

• - curved rods with bipolar flagella

significant cause of food borne gastroenteritis worldwide. Source of infection may be food, or contact with infected animals and their excreta. Zoonoses from birds most common. All ages are at risk, but in US infants have the highest incidence.

• - Virulence factors: adhesions, lipopolysaccharides with endotoxic activity, Enterotoxins, intracellular survival and ability to penetrate cells.

• - Pathogenesis: organisms invade epithelium of lower small intestines and multiplies. This produces an inflammatory response which is responsible for many of the symptoms.

• - Prevention: thoroughly cook poultry and only use pasteurized milk

Symptoms of Campylobacter jejuni

start 1-10 days after ingestion. Vagues abdominal pain, bloody diarrhea, chills and fever for 3-6 days. treatment can be with erythromycin but untreated patients this can secrete organism for several months

Clostridium difficile

• - Gram positive

• -endospore forming rods

• - normal flora of intestine in certain patients

• -caused antibiotic induced pseudomembranous colitis

• - antibiotics kill commensals, allowing C difficle to thrive.

• - Bacteria release a toxin that depolymerizes the actin filaments causing the pseudomembranous lesions associated with hemorrhagic necrosis

• - Toxin causes attraction of large amounts of PMN to the site of infection.

• - common complication of chronic antibiotic

Group D strep/ streptococcus faecalis or enterococci

Enterotoxin producing staphylococcus aureus containing 24hr, self limiting gastroenteritis here bacteria do not colonize the gut but the toxin is consumed with contaminated food.

Meningitis

inflammation of the protective membranes covering the CNS known as the meninges. Bacteria and viruses that infect the skin, urinary system, gastrointestinal system, or respiratory tract can spread by the bloodstream to the meninges through cerebrospinal fluid,

• - Most cases are both viral and bacterial result from infections that are contagious and spread via tiny drops of fluid from the throat and nose of someone who is infected, the drops may be airborne

Bacterial meningitis

rare but is usually more serious and can be life threatening if it is not treated right away

Viral meningitis (aspetic meningitis)

relatively common and less serious

• - common symptoms are fever and severe sudden headache accompanied by neck/back stiffness, mental changes or rashes

infants with meningitis

may seem extremely irritable, lethargic or have a fever. They may be difficukt to comfort when they are picked up or rocked.

diagnosis of meningitis

done by spinal puncture and extraction of CSF which is sent to lab for culture

Bacterial causes of meningitis

streptococcus pneumoniae, Neisseria meningitis, Haemophiles influenzae

streptococcus pneumoniae

leading cause of meningitis. Infection of middle ear (otitis media) may lead to meningitis. No rash, may leaf to permanent neurological sequelae (sequential consequences)

Neisseria meningitis

• - gram neg, oxidase, aerobic diplococci. Has pili for attachment and has outer membrane lipopolysaccharides

• - Virulence: virulence strains have a capsule, pili and LPS. Anti-capsular opsonic antibiotics are protective

• - the nasopharynx is the only reservoir. upon infection it first takes residence on the mucosal membrane surfaces of nasopharyngeal areas by attaching with pili it then infects deeper into the tissue, until it gains access to the bloodstream where it then travels to infect the meninges of the brain.

• -IT IS THE ONLY BACTERIA KNOWN TO CAUSE EPIDEMIC MENINGITIS

meningococcal menigitis

most commonly affects individuals 3 years and adolescents,

• - Invasiveness: infection of nasopharynx is subclinical and resolves within several weeks.

• - In a few individuals, organisms invade the circulation and cause clinical disease which include: an uncomplicated bacteremia process, a systemic infection that commonly involves the meninges (3% mortality rate), or a severe systemic meningococcemia (sepsis) with dissemiated intravascular coagulation (DIC) circulating and necrotic petechial rash (50% mortality rate)

Waterhouse Friderichsen syndrome (WFS)

complication involving massive, usually bilateral hemorrhage into the Adrenal glands caused by severe meningococcemia

• - Therapy: penicillin is the drug of choice to treat meningococcemia and meningococcal meningitis. Must DIAGNOSE QUICKLY. Rifampin for chemoprophylactic use (for exposed people)

• - Prevention: there are 12 types Neisseria meningitis capsular polysaccharide that cause disease

• - Most important serogroups are : A, B,C, Y and W135

Which Serogroup causes the most cases of Neisseria meningitis capsular polysaccharide?

serogroup B

What are the two vaccines for Neisseria meningitis capsular polysaccharide?

MPSV4/ Menomune and MCV4, both vaccines can prevent 4 types of meningococcal diseases (serogroup A, C, Y and W-135)

which vaccine is recommended for all children for Neisseria meningitis capsular polysaccharide?

MCV4, recommended for preadolescents (11-12). For those who have never gotten Menactra previously a dose is recommended at high school entry. Also recommended for college freshmen living in dorms and US military recruits.

What are Bexero and Trumemba vaccines given for?

stereotype B

Haemophilus Influenzae

• - Gram neg, pleomorphic rods, grows in chocolate agar which contains NAD and Heme (lysed RBC)

• - Pathology: lives in human Respiratory tract, most strains are opportunistic pathogens, which means they cause disease secondary to infection.

Encapsulated Haemophilus Infleunzea

are the pathogenic ones—→ capsule Type B (Hib) is the most pathogenic one, Hib was the most important causes of bacterial infections in young children ages 2-4. Hib caused diseases like meningitis, epiglottis, sepsis, pneumonia and arthritis.

• - Incidence of invasive Hib disease has decreased in children

Uncapsulated Haemophilus Infleunzea

Non type B, causes otitis media and conjunctivitis and sinusitis in children, also associated with pneumonia.

• - Therapy: high mortality if not treated, treat with IV 3rd gen cephalosporin. High risk for post infection neurological sequelae.

What are the 2 types of Hib vaccines?

• - Hib: polysaccharide (PRP) vaccine- mounts a T independent response, not appropriate for infants, helpful for older children and adults

• - Hib conjugate: carbohydrate capsule is conjugated to a protein (diphtheria toxoid) to make it more immunogenic

How do T cells work with conjugated vaccines?

carbohydrate antigens alone cannot activate Th2 cells. One can use a protein conjugate to present peptide antigens to Th2 cells. Improves immune respone, resulting in high affinity IgG. —→ B cell binds to bacterial polysaccharide component of vaccine conjugate—→ conjugate is internalized and degraded—→ peptides from the toxoid are presented to the T cell, which activates the B cell—→ activated B cell differentiates into a plasma cell that produces anti-polysaccharides antibodies that bind to bacteria.