Micro 8
Factors that allow invasion of the central nervous system
- Capsule (helps reach BB barrier) - Uncharged - Small - Lipid soluble Factors that can open up blood-brain barrier: - Microwaves - Radiation - Trauma - Hypertension - Infection
How to diagnose and treat Neonatal Disease (caused by Streptococcus agalactiae)?
(Chemoprophylaxis used if suspected) Intrapartum temperature of 38 degrees C Membrane rupture > 18 hours before delivery Vaginal or rectal cultures positive at 35-37 weeks gestation Treat mom 4 hours before delivery Working on a vaccine for Streptococcus agalactiae
Rickettsia rickettsia basic infection diagram (Rocky Mountain Spotted Fever).
(Strict intracellular parasite, most common rickettsia) 1. R. rickettsii infection of an endothelial cell. Phagocytosis is induced. 2. In cell with phagosome 3. Bacterium escapes from phagosome- forms an actin tail. 4. Bacterium escapes the membrane by using its actin tail. * Must escape phagosome into cytoplasm to survive. Cells grow in cytoplasm/ nucleus and continually released. *
Virulence factors of Neisseria
*Pilus*: Aids attachment to human mucosal epithelium; contains constant and hypervariable regions- analogous to immunoglobulins (Igs) - that contribute to antigenic diversity in gonococci. *Por proteins*: Form pores through outer membrane; antigenic; specific serotypes associated with virulence. *Opa proteins*: Assist binding to epithelial cells *LOS*: Lipooligosaccharide (endotoxin activity) *Rmp proteins*: Inhibit 'cidal' activity of serum. *IgA protease*: Core contains enzyme; released by cell to destroy IgA1. *Capsule*: Resists phagocytosis, unless antibody present.
Diagnosis of Streptococcus pneumoniae
*unilateral* acute otitis media (sign of streptococcus pneumoniae in young children) Diagnose via: - Alpha hemolytic - Optochin test sensitive - Bile solubility test is bile soluble
Rickettsiae infections characteristics and typical clinical symptoms
- Gram negative, aerobic rods - Obligate intracellular - Arthropod transmitted - Small bacteria Multisystem infections, may persist in body or become latent. Clinical features: Fever, headache, rash, history suggesting contact with rickettsial vector.
Staphylococcus saprophyticus identification
- Gram positive coccus - Catalase positive - Coagulase negative - Mannitol salt negative (pink/red on manitol salt (Staph aureus on the other hand are catalase and coagulase positive and turns yellow on mannitol-salt agar)
Viral meningitis
- Milder than bacterial - Headache, fever, photophobia - Less nuchal rigidity
Streptococcus pneumoniae
- SPIN- Strep pneumoniae in neonates. - Rare but high mortality. - Associated with: - premature membrane rupture - Maternal colonization, infection - Prematurity ---------------------------------- Source: Resident flora/respiratory droplets Most likely candidate: Very young or very old. Why: Weak immune systems Causes: - Acute otitis media (in young children) - Sinusitis - Pneumonia - Meningitis - Bacteremia
Laboratory diagnosis of Rickettsia Rickettsii (Rocky Mountain Spotted Fever)
- Stain poorly with gram stain - need *Giemsa* - Fluorescent staining of biopsy materials- reference labs - Nucleic acid based tests- insensitive for blood samples. - Culture - need experience - MIF (Microimmunofluorescent test) - Antibodies against outer membrane proteins (species specific) and LPS antigen - Sensitivity and specificity is high - Reference labs mostly
Infections in pregnant women
-Postpartum Endometritis (inflammation of inner lining of uterus) - Wound infection - UTI - Prognosis excellent - Meningitis would be rare
Life cycle of rhipicephalus sanguineus (brown dog tick) and the transmission of Rickettsia rickettsii (causitive agent of Rocky Mountain Spotted Fever).
1. Adult female drop off host to lay eggs. 2. Eggs hatch into six-legged larvae. (possibility exists for transmission from larvae (infected transovarially) to humans but requires further investigation). 3. Larvae feed on first host and may acquire R. rickettsii (Dog host) 4. Larvae molt into nymphs after leaving first host (most likely dog). (Infected nymphs may feed on humans and transmit R. rickettsii). 5. Nymphs feed on second host and may acquire R. rickettsi. 6. Nymphs molt into adults after leaving second host. (infected adults may feed on humans and transmit R. rickettsii). 7. Adults attach to the third host for feeding and mating and may acquire R. rickettsi. 8. Repeat. Life cycle of Rickettsia rickettsii, the etiological agent of Rocky Mountain Spotted Fever: Larvae -> rodent -> nymph -> adult tick -> Canine (then to humans) or straight to humans. (Adult tick can also just go and lay eggs which -> larvae and cycle continues).
Naegleria Fowleri (protozoal amoeba) life cycle
1. Cyst in the water 2. Turns to trophozoite in the water (infective stage) 3. Can convert to temporary non-feeding flagellated form (usually reverts back to trophozoite stage) or undergo cell division (promitosis). (Flagellated forms can also cause meningitis) 4. Trophozoites infect humans or animals by penetrating the nasal mucosa. 5. Migrate to the brain via the olfactory nerves causing Primary Amoebic Meningoencephalitis (PAM). Diagnosis via *Trophozoites in CSF and brain tissue. Flagellated forms occasionally in CSF* ----Water-related activities such as swimming underwater, diving, or other water sports can result in water going up the nose *keep head above water*.
Borrelia burgdorferi transmission cycle
1. Infected or uninfected adult female (Blacklegged Tick- Ixodes scapularis) -> Uninfected eggs -> Uninfected larvae -> 1st blood meal (rodent) -> infected nymph -> Primary route: infected human. Infected nymph -> 2nd blood meal (rodent) -> Infected adult -> Secondary route: infected human. Infected adult -> 3rd blood meal, adult mating (deer) -> cycle repeat. Organism is in salivary gland, has to be on you for ~24 hours for this reason for transmission. (Feeding of infected nymph -> amplification in the midgut (TROSPA Salp25D) -> Crossing of the midgut barrier (tre31) -> infection of salivary glands -> (Salp15 tHRF TSLPI) Humans.)
Strategies to identify women who require IAP (intrapartum antibiotic prophylaxis) for Streptococcus agalactiae
1. Universal Screening for GBS (Group B Streptococcus) in 35-37 weeks of gestation to identify carriers. -> *Antenatal*: Maternal colonisation of the vaginal tract by Group B Streptococcus (GBS) -> *Perinatal*: Intrapartum transmission of GBS to neonate. 2. Identification of risk factors: - Prematurity - PROM (premature rupture of membrane) - Intrapartum pyrexia - GBS bacteriuria identified antenatally - Previous invasive GBS disease 3. GBS PCR rapid diagnostic tests. Both 2 and 3 -> *Perinatal* *Perinatal* -> In utero infiltration of amniotic fluid by GBS progressing to invasive neonatal infection. Or -> Direct acquisition through birth canal. *Intrapartum antibiotics- reduces vertical transmission from mother to baby* . In utero infiltration of amniotic fluid by GBS progressing to invasive neonatal infection. -> Early-Onset GBS Disease (Early recognition of neonatal GBS disease and prompt treatment at this step). Direct acquisition through birth canal -> Early-Onset GBS Disease or -> neonatally acquired GBS colonisation (Hospital, community, environmental sources of GBS) ->Late-Onset GBS Disease.
Escherichia coli and Proteus mirabilis identification
Escherichia coli - Gram negative rod - Lactose fermenter - Indole positive Proteus mirabilis - Gram negative rod - Lactose nonfermenter - Urease positive
Vaccine for Neisseria meningitidis (meningococcal disease)
2 types available in USA: -Meningococcal conjugate vaccines (Menactra and Menveo) - Does not include B and -Serogroup B meningococcal vaccines (Bexsero and Trumenba) All 11 to 12 year olds should be vaccinated with a meningococcal conjugate vaccine. Teens and young adults (16 through 23 year olds) also may be vaccinated with a serogroup B meningococcal vaccine. In certain situations, other children and adults could be recommended to get meningococcal vaccines.
Clinical presentation of Rickettsia Rickettsii (Rocky Mountain Spotted Fever)
About 7 days after tick bite - High fever, headache - Macular rash - 90% of patients after 3 days: - Centripetal spread (from extremities upwards). - Palms and soles can be involved - Rash evolves to petechial "spotted" -Delay in diagnosis has poor prognosis.
Neisseria meningitidis disease presentation
Acute onset of headache and fever Nuchal rigidity (neck stiffness) Petechiae on trunk Children - less specific signs/symptoms.
Which ticks spread Rickettsia rickettsii disease? (Rocky Mountain Spotted Fever) Majority of infections found? Timing (months)?
American dog tick - Dermacentor variabilis - SE states, West Coast Brown dog tick - Rhipicephalus sanguineus - AZ Wood tick - Dermacentor andersoni - Rocky Mountain States and SW Canada Majority of infections: - North Carolina, Oklahoma, Arkansas, Tennessee, and Missouri. Timing: April to September. (4 to 9, spring and summer)
What is meningococcal disease
Any disease caused by Neisseria meningitidis including meningococcemia and meningitis.
Bacteremia vs Septicemia
Bacteremia = bacteria in the blood Septicemia = infection in the blood
Organisms covered in urine
Bacterial - Escherichia coli- most common, *review Pap pili as virulence factor* - Proteus mirabilis- associated with urinary stones (calculi) - Staphylococcus saprophyticus- young, sexually active female Protozoal - Schistosoma haematobium (review slides from Fungi and Parasites lecture)
Organisms covered in brain- bacterial, fungal, parasitic, and viral
Bacterial: - Streptococcus agalactiae - Escherichia coli - Streptococcus pneumonia - Neisseria meningitides - Haemophilus influenza Fungal: - Cryptococcus neoformans Parasitic: - Naegleria fowleri - Baylisascaris Viral: - Rabies virus
What are the bacterial, parasitic, and viral blood organisms covered in this lecture?
Bacterial: Rickettsia rickettsia, Rickettsia prowazekii, and Borrelia burgdorferi. Parasitic: Plasmodium falciparum, Trypanosoma cruzi, and Trypanosoma brucei. Viral: Ebola.
Epiglotitis
Caused by Haemophilus influenza type b - Acute, severe cellulitis of the epiglottis - Abrupt onset - epiglottis swells - Acute inflammation - Edema with infiltration of PMN's - Consider a true emergency ----------------------------- Presentation in children: Predominantly boys aged 2-3 Three D's: - Drooling - Dysphagia - Distress Presents with high fever Cherry red epiglottis Tachypnea Auscultation - Inspiratory stridor - Expiratory rhonchi -------------------------------- Capsule - Polyribitol phosphate (a polysaccharide) - Type B was most common, now c, f. - Vaccine based on type b ------------------------------ Highest risk for epiglottitis: - Unvaccinated - no anti-PRP antibodies - Depletion of complement - Splenectomy ------------------------------- Diagnosis: Be careful with these patients! - Keep upright - Maintain patent airway Laryngoscopic evaluation: - With trained personnel standing by ready to intubate - Suggested all pediatric patients be intubated.
Bayliascaris life cycle
Baylisascaris procyonis completes its life cycle in raccoons, with humans acquiring the infection as accidental hosts (dogs serve as alternate definitive hosts, as they can harbor patent infection and shed eggs). Unembryonated eggs are shed in the environment where they take 2-4 weeks to embryonate and become infective. Raccoons can be infected by ingesting embryonated eggs from the environment. Additionally, over 100 species of birds and mammals (especially rodents) can act as paratenic hosts for this parasite: eggs ingested by these hosts hatch and larvae penetrate the gut wall and migrate into various tissues where they encyst. The life cycle is completed when raccoons eat these hosts. The larvae develop into egg-laying adult worms in the small intestine and eggs are eliminated in raccoon feces. Humans become accidentally infected when they ingest infective eggs from the environment; typically this occurs in young children playing in the dirt. Migration of the larvae through a wide variety of tissues (liver, heart, lungs, brain, eyes) results in VLM (visceral larval migrans) and OLM (optical larval migrans) syndromes, similar to toxocariasis. In contrast to Toxocara larvae, Baylisascaris larvae continue to grow during their time in the human host. Tissue damage and the signs and symptoms of baylisascariasis are often severe because of the size of Baylisascaris larvae, their tendency to wander widely, and the fact that they do not readily die. Diagnosis is usually made by serology in patients who have clinical disease compatible with baylisascariasis, or by identifying larvae in biopsy or autopsy specimens.
Difference between blood-brain barrier and blood-CSF barrier
Blood-brain barrier: -Endothelium without fenestrations - Thick basement membrane - Astrocyte footplates Blood-CSF barrier: - Endothelium that is fenestrated - Thin basement membrane - Choroid plexus epithelium on CSF.
Clinical presentation of lyme disease
Borrelia burgdorferi via Blacklegged Tick (Ixodes scapularis) -Incubation of 1 week - Fever, headache, myalgia, lymphadenopathy - Erythema migrans - characteristic lesion. Fatigue is the main symptom of both early and chronic lyme. Chronic lyme has cognitive, neuropathy, depression, and heart related issues as well that is absent in early lyme. (Know the chart)
Virulence factors in bacterial meningitis
Both Neisseria meningitidis and Haemophilus influenzae have: Capsule IgA protease Pili Endotoxin Outer membrane proteins. Streptococcus pneumoniae has: Capsule and IgA protease (lacks pili, endotoxin, or outer membrane proteins).
CDC recommendation for vaginal strep B
CDC recommended routine screening for vaginal strep B (Streptococcus agalactiae) for all pregnant women. This screening is performed between the 35th and 37th week of pregnancy. Studies show that testing done within 5 weeks of delivery is the most accurate at predicting the GBS status at birth.
Capsule of S. Agalactiae (Group B strep)
Capsule - Polysaccharide - Antibody protective - *Most important virulence factor* Clinical importance: Vaginal colonization - Bladder infections - Premature delivery - Prolonged membrane rupture - Postpartum fever Transmitted to infants during birth. Consequences? - *Neonatal disease.*
Malaria life cycle
Causal agent: Plasmodium (*P. falciparum (main)*, P. vivax, P. ovale and P. malariae) found in tropical and subtropical areas. The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host (infective stage) (Exo-erythrocytic cycle, human liver stages) #1. Sporozoites infect liver cells #2. and mature into schizonts #3. which rupture and release merozoites #4. (Of note, in P. vivax and P. ovale a dormant stage [hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later.) (Human blood stage) After this initial replication in the liver (exo-erythrocytic schizogony The letter A), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony The letter B). Merozoites infect red blood cells # 5. The ring stage trophozoites mature into schizonts, which rupture releasing merozoites # 6. Some parasites differentiate into sexual erythrocytic stages (gametocytes) # 7. Blood stage parasites are responsible for the clinical manifestations of the disease. The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal # 8. The parasites' multiplication in the mosquito is known as the sporogonic cycle The letter C. While in the mosquito's stomach, the microgametes penetrate the macrogametes generating zygotes # 9. The zygotes in turn become motile and elongated (ookinetes) # 10 which invade the midgut wall of the mosquito where they develop into oocysts # 11. The oocysts grow, rupture, and release sporozoites # 12, which make their way to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle .
Bayliascaris
Caused by roundworms found in raccoon (primary/definitive host) - Infected by eating eggs of larvae - Infected by eating rodents, rabbits, birds infected with larvae - Have universal latrine- where eggs passed. Children likely to ingest on hands Larvae travel to brain/spinal cord/eye Could go to other organs too ------------------------------- Clinical presentation Infected with eggs or larval stage and it cannot complete life cycle Dependent on number of larvae in infecting dose and location Neural larval migrans - Weakness, uncoordinated, altered mental status, seizures, stupor - Damage is already done by time recognized Optical larval migrans - Photophobia, retinitis, blindness Visceral larval migrans - Rash, enlarged spleen, pneumonitis
African Trypanosomiasis characteristics ("sleeping sickness")
Caused by the protozoan parasite Trypanosoma brucei. Transmitted by the tsetse fly only found in rural Africa. 2 different subspecies both caused by tsetse flies living in woodlands and thickets. Occasionally caused by congenital (mother to unborn baby). Disease involved 2 stages: first stage in peripheral circulation, second stage when crossing blood-brain barrier. T.b. Rhodesiense (East African sleeping sickness) Cattle spread disease- main reservoir of infection. -First large sore (chancre) at bite site, fever, headache, muscle/joint aches, enlarged lymph nodes 1-2 weeks after infection. Some develop rash. -After few weeks crosses blood brain barrier and causes: Mental deterioration and other neurologic problems. Death ensues within months. T.b. gambiense (West African sleeping sickness)- Parasite responsible for most sleeping sickness. Humans are main reservoir of infection. Progresses more slowly. -First same symptoms of T.b. Rhodesiense. -After 1-2 years there is evidence of CNS involvement including: Personality changes, sleep disturbance, progressive confusion, partial paralysis, balance/walking abnormality, and hormonal imbalance. Usually kills in about 3 years.
Chagas disease (American trypanosomiasis) characteristics
Caused by the protozoan parasite Trypanosoma cruzi. Infection through contact with feces of infected triatomine bug ("kissing bug" blood-sucking insect). Endemic in Mexico, Central America, and South America, rural, poor areas. Infection can also occur from: Mother-to-baby (congenital), transfussions, organ transplant, lab accident, contaminated food or drink (rare). Has acute and chronic phase. Acute: fever or swelling around site of inoculation. Following acute phase, most infected enter a prolonged asymptomatic form of disease ("chronic indeterminate") which few or no parasites found in the blood. People unaware they are infected and may remain asymptomatic for life;however, 20-30% will develop severe symptoms. Complication of chronic Changas disease: Heart rhythm abnormalities that can cause sudden death Dilated heart that doesn't pump blood well Dilated esophagus or colon, leading to difficulties with eating or passing stool. Extra: Romana's sign- swelling of child's eyelid is marker of acute Chagas disease (rubbed the eye w/ bug feces or was bit there).
Haemophilus influenza type b diagnosis
Chocolate agar Gram negative coccobacillus X and V factors for growth.
Collecting blood draws for septicemia in adults, children, and neonates.
Collect prior to administering antibiotics if possible. Adults- collect 20 ml/culture Children - collect 5-10 ml/culture Neonate- collect 1 ml/culture.
CAMP test
Confirmatory test for group B Strep. (Strep. agalactiae), unknown beta Strep. is streaked perpendicular to Staph. aureus on blood agar.
Laboratory diagnosis of Streptococcus agalactiae
Culture LIM broth- has antibiotics added to suppress growth of other organisms - Subculture to blood agar Antigent test- too insensitive for screening.
Urine organisms cause?
Cystitis- inflammation of the bladder Pyelonephritis- Kidney infection
Neonatal Disease
Early onset (< 7 days old) - Bacteremia- most common cause - Pneumonia - Meningitis- most common cause - Survive but have severe consequences such as blindness, deafness, mental retardation. Symptoms: - Fever - Lathargy - Difficulty feeding Late onset (1 week to 3 months) - Bacteremia with meningitis - Mortality low but neurologic complications common - Exogenous source Signs and symptoms: - Difficulty breathing - Fever - Lethargy - Difficulty feeding - Irritability
Neisseria meningitidis epidemiology
Endemic - regularly found among particular people or in a certain area. Spread by respiratory droplets Humans are the only carriers Military College students
Most likely organism for UTI
Escherichia coli: - Most common cause - Pap pili - Source of organisms- endogenous. - Positive indole test Proteus mirabilis: - Most commonly seen in blockage from urinary or kidney stones. - Produces urease, raises pH - Urea test positive and urease test positive. - Distinctive growth on blood agar- swarming Staphylococcus saprophyticus - Sexually active young women.
What is Ebola Virus Disease?
Family *Filoviridae* Caused by infection with a group of viruses within the genus Ebolavirus: - Ebola virus (species Zaire ebolavirus) - Sudan virus (species Sudan ebolavirus) - Tai Forest (Species Tai Forest ebolavirus) - Bundibugyo virus (species Bundibugyo ebolavirus). Ebola virus spreads to people through direct contact with bodily fluids of a person who is sick with or has died from EVD. This can occur when a person touches the infected body fluids (or objects that are contaminated with them), and the virus gets in through broken skin or mucous membranes in the eyes, nose, or mouth. The virus can also spread to people through direct contact with the blood, body fluids and tissues of infected fruit bats or primates. People can get the virus through sexual contact as well. Ebola survivors can experience side effects after recovery including tiredness, muscle aches, eye and vision problems and stomach pain. No approved treatment or vaccine exists at this time.
Risk factors and diagnosis for UTI
Female Post menopausal decrease in estrogen Blockages such as kidney stones or enlarged prostate Diabetes Catheterized patients Holding urine for extended periods of time
Encephalitic Rabies symptoms
Fever Hydrophobia Pharyngeal spasms Hyperactivity subsiding to paralysis, coma, death - Hypersalivation - Lacrimation - Sweating
Two-Tiered testing for Lyme Disease (Borrelia burgdorferi via Blacklegged Tick (Ixodes scapularis))
First test: Enzyme immunoassay (EIA) or Immunofluorescence Assay (IFA). If negative consider alternative diagnosis or if patient with signs/symptoms consistent with Lyme disease for less than or equal to 30 days, consider obtaining convalescent serum. If positive and sign/symptoms less than/equal to 30 days = IgM and IgG Western Blot. If positive and sign/symptoms greater than/equal to 30 days = IgG Western Blot ONLY.
Paralytic Rabies
Flaccid paralysis especially in bitten limb Headache, pain, mild sensory disturbance Ascending paralysis - Paraplegia - Loss of sphincter tone - Paralysis of muscles of swallowing and respiration - Death
Streptococcus agalactiae other populations
Generally older population Debilitating condition present Bacteremia, pneumonia, bone and joint infections, skin and soft tissue infections Again not likely to be meningitis Do have higher mortality because of predisposing condition
Laboratory profile for CSF
Glucose goes down because the bacteria/fungi consumes the glucose.
Diagnosis of Neisseria meningitidis
Gram stain - gram-negative diplococci in CSF.
Streptococcus agalactiae (Group B)
Gram stain: -Gram positive cocci Hemolysis: -Majority beta hemolytic -Small zone of hemolysis Lancefield grouping (grouping catalase-negative, coagulase-negative bacteria based on the carbohydrate composition of bacterial antigens found on their cell walls): - B grouping
What is the most common cause of life-threatening infection in newborn babies?
Group B Strep (Streptococcus agalactiae)
Haemophilus Influenzae Type B
H. Influenzae Type B Meningitis symptoms: Altered cry: - High pitched - Weakened - Uncontrollable Lethargy Seizures - typically why patient brought to ED.
Prevention of meningititis and epiglottitis
Hib vaccine- conjugate - PRP-HbOC conjugated with nontoxic diphtheria toxin. - PRP-OMP conjugated with outer membrane protein of Neisseria meningitidis - PRP-T conjugated with tetanus toxoid - PRP- D conjugated with diphtheria toxoid *Not recommended or liscensed for children < 12 months* Receive at 2, 4, 6 months of age. -------------------------------- Why is conjugate vaccine necessary? - Infants cannot generate immune response to polysaccharides - Need protein carrier What immune response is activated? - Cell-mediated - T-cell dependent antigen
Prevention of rabies
Human rabies immunoglobulin Rabies vaccine - 4 shots over 14 days - Inactivated vaccine using attenuated virus
Rabies virus (family rhabdovirus, genus lyssaviruses) life cycle
If bitten on leg, have some time until it gets in the brain. 1. Bite on leg- virus inoculated. 2. Viral replication in muscle 3. Virus binds to nicotinic ateylcholine receptors at neuromuscular junction 4. Virus travels within axons in peripheral nerves via retrograde fast axonal transport. 5. Replication in motor neurons of the spinal cord and local dorsal root ganglia and rapid ascent to brain 6. Infection of brain neurons with neuronal dysfunction. 7. Centrifugal spread along nerves to salivary glands, skin, cornea, and other organs.
Clinical presentations of Lyssaviruses (Rhabdovirus- rabies)
Incubation period - 1 to 3 months - Could be days to years Prodromal - Flu like symptoms - Occasionally photophobia - Prickling, tingling, itching, burning at site Rabies - Encephalitic - Paralytic
4 causes of sepsis
Lung infections (pneumonia) Urinary tract infections Skin infections Infections in GI tract.
Meningococcemia vs Meningitis
Meningococcemia: Neisseria meningitidis *blood infection* (enters through nose and throat). Causes: -*Purplish rash* which is a telltale symptom, pale or mottled skin (petechiae). - Unusually cold hands and feet - Breathing fast and breathlessness - Limb, joint, and muscle pain Meningitis: Neisseria meningitidis *Spinal cord/brain infection* (enters through nose and throat). Causes: - *Severe headache and stiff neck* - Sensitivity to bright light - Seizures BOTH CAUSE: - Very sleepy & vacant - High fever - Confused & delirious - Vomiting
Malaria diagnosis
Microscopy = gold standard, visualized on both thick and thin blood smears stained with Giemsa, Wright, of Wright-Giemsa stains. *Giemsa* is the preferred stain and allows for detection of certain morphologic features (e.g. schuffner's dots, Maurer's clefts, etc.) Thick smears detect presence of parasites while thin smears are used for species-level identification. Quantification may be done on both thick and thin smears. *P. falciparum*: Stages found in blood include: Ring form trophozoite: RBC appearance- normal; multiple infection of RBC more common than in other species; Maurer's clefts (under certain staining conditions) Appearance of parasite- delicate cytoplasm, multiple infection, 1-2 small chromatin dots. Trophozoite: RBC appearance- normal; rarely, Maurer's clefts (under certain staining conditions) Appearance of parasite- Seldom seen in peripheral blood; compact cytoplasm; dark pigment Schizont: RBC appearance- rarely, Maurer's clefts (under certain staining conditions) Appearance of parasite- seldom seen in peripheral blood; Gametocyte (distorted by parasite): Crescent shape.
Diagnosis for UTI
Midstream urine sample Dipstick reading Culture ------------------------------ Urinary specimen collected "clean catch" Midstream urine - >10^5 bacteria/mL - Single species - Either transported to lab ASAP or refrigerated - Dipstick -*Leukocytes*- Increased concentration may indicate infection in kidneys and urinary tracts. In bacterial urinary tract infection leukocytes are in most cases found in the urine. -*Nitrite*- Positive test results may indicate urinary tract infection. *Gram-negative* bacteria converts nitrate to nitrite in the bladder. -*Urobilinogen*- Increased concentration may indicate liver cell damage or increased bilirubin excretion to intestines. -*Protein*- May indicate kidney disease. -*pH*- Indicates urine acidity level. Acidic urine may be caused by kidney disease but also by diet. - *Blood*- Increased concentration may indicate infection or disease in kidney and bladder. - *Specific Gravity*- Increased concentration may give information on the kidneys' ability to concentrate urine in relation to plasma. - *Ketones*- Increased concentration may be associated with diabetes, low-carb diets or starvation. - *Bilirubin*- Increased concentration may indicate liver damage. - *Glucose*- Increased concentration may indicate diabetes mellitus.
Neisseria species
Neisseria gonorrhoeae Neisseria meningitidis Neisseria species: - Normal flora - Nonpathogenic
Pathogen (Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus agalactiae (Group B), and Escherichia coli) and their capsule, important type, and vaccine?
Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, and Escherichia coli all have polysaccharide capsules. Streptococcus agalactiae (Group B) have polysaccharide rich in sialic acid. Important type of capsule: Neisseria meningitidis- A, B, C, Y, W-135 Haemophilus influenzae- B Streptococcus pneumoniae - 94 Streptococcus agalactiae (group B) - (Ia, Ib, II) III in neonatal meningitis Escherichia coli - K1 in meningitis Vaccine: Neisseria meningitidis- A, C, Y, W Quadrivalent vaccine. B Vaccine. Haemophilus influenzae- Hib vaccine for < 1 year old. Streptococcus pneumoniae - PCV13 and PPSV23 Streptococcus agalactiae (group B) - In development Escherichia coli - None
Malaria clinical presentation
Non-specific and the diagnosis can often be missed. Untreated malaria can progress to severe forms that may be rapidly (<24 hours) fatal. Most frequent symptoms include fever and chills which can be accompanied by headache, myalgias, arthralgias, weakness, vomiting, and diarrhea. Other clinical features include splenomegaly, anemia, thrombocytopenia, hypoglycemia, pulmonary or renal dysfunction and neurologic changes. Infections caused by P. falciparum are most likely to progress to severe, potentially fatal forms with central nervous system involvement (cerebral malaria), acute renal failure, severe anemia, or acute respiratory distress syndrome.
Clinical presentation of PAM
PAM = Primary Amoebic Meningoencephalitis- Caused by Naegleria Fowleri (protozoal amoeba) - Symptoms start about 5 days (range 1 to 9 days) after infection. - The initial symptoms may include: Headache, fever, nausea, or vomiting, altered sense of smell - Later symptoms include: Stiff neck, confusion, lack of attention to people and surroundings, loss of balance, seizures, and hallucinations. After the start of symptoms, the disease progresses rapidly and usually causes *death* within about 5 days (range 1 to 12 days).
Main virulence factors of Neisseria
Pili - Antigenic variation - Phase Variation Lipooligosaccharide Capsule - Polysaccharide - Antigenic - Serotypes - polysaccharides - B - weak antigen, related to neurologic tissue. - A, C, Y and W135- have had vaccine for quite awhile.
Virulence factors of Streptococcus pneumoniae
Polysaccharide capsule 90+ serotypes What contribution does capsule have for pathogenesis? -Required for virulence -Evades immune system What contribution does capsule have for vaccines? -90+ serotypes -Most common are PPSV23 (Polysaccharide vaccine): For all adults 65 and older, certain high risk younger population. and PCV13 (Conjugate vaccines): -For 6 weeks through 71 months. -Age 19+ with immunocompromising conditions - NOT recommended at this time by ACIP for healthy adults- but FDA approved. - Need 4 doses (2-3-6-12/15 months) - Adults 65 and older - 1 dose. Also other forms of conjugate vaccines including PCV7.
Review these case studies
Rabies: https://www.cdc.gov/mmwr/volumes/65/wr/mm6521a1.htm?s_cid=mm6521a1_w Naegleria Fowleri: https://www.cdc.gov/mmwr/volumes/65/wr/mm6516a4.htm?s_cid=mm6516a4_w
Rabies encephalitis
Rhabdovirus - Bullet shaped, ssRNA negative strand, enveloped virus Excreted in saliva of infected dogs, foxes, jackals, wolves, skunks, raccoons, vampire and other bats (can infect all warm-blooded animals). Dogs source of 99% of cases worldwide Transmission - Bite - Salivary contamination of abraded/wounded skin (Case report- During recent decades, most domestically acquired human rabies cases in the United States have been associated with bat exposures (silver-haired bat); however, in the majority of these cases, no bite was reported.
Which way is Rickettsia Rickettsii transmitted? Borrelia burgdorferi transmitted? Transovarially or Transstadial?
Rickettsia = Transovarially Borrelia = Transstadial
Typhus
Rickettsia prowazekii Growth cycle differs from spotted fever. Growth intracellularly results in cell lysis. - Lack required gene to take over host actin to escape cell. Caused by: Human body louse (Pediculus humanus). Epidemic or louse borne typhus. Clinical presentation: -Rickettsia prowazekii multiply in gut of louse -Excreted in feces during biting -Scratch site- organisms inoculated into skin -Need reservoir of infected people - Was more prevalent in wartime - Can terminate by delousing compaigns - 10 to 14 days after bite - Fever, headache, flu-like symptoms - Rash 5-9 days later - maculopapular - 80% develop neurologic involvement- meningoencephalitis with delirium and coma
ACIP recommendations for use of Meningococcal Vaccine
Routine vaccination of adolescents with MCV-4 (conjugate vaccine). - Individuals age 11-18 - Microbiologists who are routinely exposed to isolates of Neisseria meningitidis - Military recruits - Persons who travel to, or reside in, countries in which N meningitidis is hyperendemic or epidemic. - Complement-deficient and asplenic (not normal spleen function) patients.
Meningococcemia
Septicemia Petechiae become larger hemorrhagic lesions Disseminated Intravascular Coagulation (DIC) Patients typically present with less pronounced onset- more flu-like. Life threatening
Meningococcal incidence by serogroup and age-group, 2007-2016
Serogroup B is a bigger factor in <1 year olds. Serogroup ACWY is a bigger factor in >65+.
Borrelia burgdorferi (Lyme disease)
Spirochete Does not stain well with gram stain - Outer membrane similar to gram negative Giemsa stain, fluorescent, dark field Can culture but not high success rate.
What are the 2 (organisms) most common causes of sepsis
Staphylococcus aureus Escherichia coli
Neonatal meningitis- bacteria with capsules (4)
Streptococcus agalactiae- Group B strep Streptococcus pneumoniae - Children and elderly - Vaccine to capsule, is conjugate vaccine for infants Haemophilus influenza type b - Most serious sequelae - Hib vaccine to capsule, is conjugate vaccine. Escherichia coli K1 - Capsule immunologically same as N. Meningitides capsule serotype Group B - Passes from mother to child at birth.
Ebola virus symptoms and diagnosis
Symptoms may appears anywhere from 2 to 21 days after contact with virus (8-10 day average) and include: Fever, severe headache, muscle pain, weakness, fatigue, diarrhea, vomiting, abdominal pain, and unexplained hemorrhage (bleeding or bruising). Diagnosis: for diagnosis there must be a combination of symptoms of EVD and a possible exposure to EVD within 21 days before the onset of symptoms. Ebola virus can be detected in blood following onset of symptoms, most notably fever. *It can take up to 3 days after symptoms start for the virus to reach detectable levels.*
Symptoms/signs of UTI
Symptoms: Urge to empty bladder even when just emptied Pain or burning on urination Cloudy or bloody urine Pain in lower abdomen or back ------------------------------- Signs: Chills or night sweats Fever Pain in side, back, or groin area Flushed or reddened skin Nausea or vomiting Elderly- only sign may be mental changes or confusion.
Diagnosis of septicemia
Take a venous blood draw and place in 2 bottle one aerobic and the other anaerobic and then incubate them. Subculture days 1 & 3. Hold at least 3 weeks, some organisms require 4 weeks.
Protozoal - Naegleria Fowleri
Thermophilic, free living amoeba Warm fresh water and swimming pools Feeds on bacteria Causes PAM- primary amoebic meningoencephalitis Rapid onset, high mortality.
Who is at risk for sepsis?
Those with: -Chronic medical condition (diabetes, cancer, lung disease, kidney disease) -Immunocompromised -Community acquired pneumonia -Previous hospitalization -Children younger than 1 year of age -Adults 65 and older
Transovarial transmission vs transstadial transmission
Transovarial transmission: Transmit disease-causing pathogens from parent arthropod to offspring arthropod. (Rickettsia Rickettsii) Transstadial transmission: Pathogen remains with the vector from one life stage to the next but not transmitted to offspring (eggs). (Borrelia burgdorferi)
Lyssaviruses (Family Rhabdovirus- includes rabies)
Tropism for neural tissue Cause neuronal dysfunction, not death of neurons Migrate in retrograde direction to dorsal root ganglion Then ascend rapidly up spinal cord to brain Productive viral replication and shedding occurs in highly innervated areas such as the salivary glands. -------------------------- Pathognomonic for Rabies: Dense, ovoid intracytoplasmic inclusions. Negri bodies seen with light microscope
African Trypanosomiasis life cycle and diagnosis
Trypanosoma brucei (T.b. rhodesiense and T.b. gambiense) 1.) Infected tsetse fly injects metacyclic trypomastigotes into skin tissue. Parasites enter lymphatic system and pass into blood stream. 2.) In host, transform into bloodstream trypomastigotes and reach other blood fluids (lymph, spinal fluid, etc.) and replicate via binary fission (unlike Chagas) and cause symptoms. 3.) Tsetse fly becomes infected with bloodstream trypomastigotes which transforms to procyclic trypomastigotes then epimastigotes then metacyclic trypomastigotes in saliva. Tsetse fly- cycle takes 3 weeks. Diagnosis through laboratory methods, rely on finding parasite in body fluid or tissue by microscopy. Parasite load in T.b rhodesiense higher than in T.b. gambiense infection. T.b rhodesiense- easily found in blood, lymph node fluid or in fluid or biopsy of chancre. (Serologic testing not used) T.b gambiense- Classic method is microscopic examination of lymph node aspirate (difficult to detect in blood). Serologic testing only for screening purposes. All patient with African trypanosomiasis must have CSF examined to determine if there is CNS involvement, drug treatment depends on it. First stage treated with pentamidine second stage with suramin, melarsoprol, eflornithine, and nifurtimox.
Chagas life cycle and diagnosis
Trypanosoma cruzi 1) Triatomine insect takes a blood meal and releases metacyclic trypomastigotes in feces near bite wound. Metacyclic trypomastigotes enter through wound or intact mucosal membranes (such as conjunctiva). 2) Inside host metacyclic trypomastigotes near site of inoculation differentiate into intracellular amastigotes. 3) Amastigotes multiply by binary fission and differentiate into trypomastigotes and released into circulation as bloodstream trypomastigotes (these don't replicate) which causes symptoms. 4) Kissing bug feeds on human or animal blood that contains circulating parasites and the ingested trypomastigotes turn into epimastigotes and then infective metacyclic trypomastigotes in the kissing bug and the cycle repeats. Diagnosis: Via thick and thin blood smears with staining and microscopic examination - only works in acute phase when parasites circulating in blood. Diagnosis generally made by testing with at least 2 different serologic tests.
How do you diagnose Neisseria meningitidis
Via CSF sample collection- cerebrospinal fluid drawn from between two vertebrae via needle (aspirated) while patient in lateral recumbent. Gram stain can reveal meningitidis.
Rabies virus transmission, treatment, and fatalities
Virus transmission: - Saliva of infected animals. - 99% of human cases are caused by dog bites - Virus attacks the brain, rabies is fatal once symptoms appear. Treatment: Thorough washing of the wound with soap and vaccine injections can avoid symptoms and save lives. Seek immediate medical care if bitten. Fatalities: Rabies affects poor rural communities mostly in Asia and Africa About 1 death every 15 minutes. 40% of the victims are children younger than 15
Ebola transmission
Zoonotic disease. Initial infection through contact with infected animal such as fruit bat or nonhuman primate- afterwards, virus spreads from person to person via direct contact with: Blood or body fluids (urine, saliva, sweat, feces, vomit, breast milk, and semen) of a person who is sick with or has died from Ebola Virus Disease (EVD). Objects (such as needles and syringes) contaminated with body fluids from sick with EVD or the body of a person who died from EVD. Infected fruit bats or nonhuman primates (such as apes and monkeys) Semen from a man who recovered from ECD (through oral, vaginal, or anal sex). Ebola virus CANNOT spread to others when a person shows no signs or symptoms of EVD. Is not usually transmitted by food, mosquitoes, or other insects.
