MICROORGANISMS INVOLVED IN THE BLOODSTREAM, CNS, AND OTHER STERILE SITES (BACTERIA I)

NEISSERIA MENINGITIDIS

● Gram-negative, aerobic, diplococci (“kidney” or “coffee bean” shape)
● Fastidious bacteria, which die on inanimate objects/surface within hours
● Either encapsulated or not

35-37°C

Neisseria meningitidis grows optimally at what temperature

5-10%

Neisseria meningitidis grows optimally at what co2 %?

humans

Only natural host of N. meningitidis?

True

TRUE OR FALSE. N. meningitidis is a commensal organism of the nasopharynx.

serotyping

N. meningitidis is classified according to —-

capsular polysaccharides

The serogroups of N meningitidis is based on the —-

13

How many serogroups for N. meningitidis?

Serogroups A, B, C, W, X, and Y

cause of majority of cases of invasive meningococcal diseases worldwide

NEISSERIA MENINGITIDIS

Oxidize glucose and maltose

NEISSERIA MENINGITIDIS

Oxidase test (+)

NEISSERIA MENINGITIDIS

BAP: colonies appear as non-hemolytic, round, convex, smooth, moist, and glistening grayish with clearly defined edge

NEISSERIA MENINGITIDIS

Grow on blood agar, Mueller-Hinton agar, trypticase soy agar, and Chocolate agar

True

TRUE OR FALSE. Some strains of N. meningitidis has a decreased penicillin susceptibility.

Expression of surface adhesive proteins
Capsule polysaccharide expression
Iron sequestration mechanisms
Endotoxin

Factors that Influence the Virulence of N. meningitidis

adolescents and young adults

Carriage of N. meningitidis is highest in —-

person to person through carriers’ droplets

How is N. meningitidis transmitted?

● smoking
● close and prolonged contact
● living in close quarters with a carrier

Factors Facilitating Spread of N meningitidis

Invasive meningococcal disease

septicemia, arthritis, meningitis

Meningococcal disease

■ dysfunction in cognition
■ impairment of vision
■ hearing loss
■ limb loss
■ educational difficulties/delays in development
■ motor nerve deficits
■ problems in behavior
■ seizure

True

TRUE OR FALSE. The mechanism of how asymptomatic infections of the nasopharynx turn into meningococcemia and meningitis is currently unknown.

Meningococcal Meningitis

Others symptoms: vomiting, nausea, sensitivity to light (photophobia), and confusion (altered mental status)

Meningococcal Meningitis

In babies: irritability, may be slow or inactive, poor appetite, bulging anterior fontanelle, vomiting, abnormal reflexes

babies, preschool children, and young people

Meningococcal Meningitis mostly affects —-

meninges

Meningococcal Meningitis has acutely inflamed —-

Thrombosis

There is —- of blood vessels in Meningococcal Meningitis

thick purulent exudate

composed of polymorphonuclear leukocytes

thick purulent exudate

In meningococcal meningitis the brain is covered with —-

bacteremia or meningococcemia

Bloodstream Infections

Bloodstream Infections (bacteremia or meningococcemia)

Symptoms similar to URTI

fulminant meningococcemia

more severe (high grade fever, hemorrhagic rash, and patient may have DIC and collapse of the circulatory system/Waterhouse-Friderichsen syndrome)

Bloodstream Infections (bacteremia or meningococcemia)

○ rapid breathing
○ fatigue
● nausea or diarrhea (with or without vomiting)
● cold hands and feet
● fever and chills
● severe pain in joints, muscles, abdomen, and chest
● hemorrhagic/dark purple rash (late stage)
● thrombosis of many small blood vessels in several organs (petechial hemorrhages are observed)
● patients may have arthritis, skin lesions, and interstitial myocarditis

15/100

— meningococcal disease patients die even with antibiotic treatment

loss of limb(s), problems in nervous system/brain damage, deafness

meningococcal disease Long-term disabilities in 5 survivors:

Blood
Spinal fluid
Nasopharyngeal swab
Puncture materials from petechial hemorrhages

Specimens of Choice for meningococcal disease

Nasopharyngeal swab

usually used for surveys of carriers of meningococcal disease

Smears
Culture
Serology

Diagnostic techniques

latex agglutination test or hemagglutination tests

detect antibodies against meningococcal polysaccharides

sediments of centrifuged spinal fluid or aspirate from petechiae

Where are smears taken for meningococcal diseases?

Penicillin G

Drug of choice for meningococcal disease

Penicillin G

cannot eradicate carrier state

Chloramphenicol or 3rd generation cephalosporin

used for those with allergies to penicillin for treatment of meningococcal disease

Rifampin

For households or other close contacts of index case of meningococcal disease, what is the chemoprophylaxis used?

Immunity and Vaccine for meningococcal disease

Associated with specific, complement-dependent, bactericidal antibodies found in the serum of patients (group specific antibodies)

4CMenB (BEXsero)

○ group B vaccine containing a mixture of antigens
○ used in many parts of the world (licensed in EU)

3

How many vaccines of N meningitidis serogroups A, C, Y and W-135

1

How many vaccines of N meningitidis serogroups C and Y (USA)

Polysaccharide tetravalent vaccine

○ poorly immunogenic among children less than 18 months old, does not induce long-lasting immunity, and does not reduce nasopharyngeal carriage
○ approved as single dose vaccine for children 2 years old and older

Menomune® by sanofi pasteur

Polysaccharide tetravalent vaccine

Menactra

Tetravalent conjugate vaccine

Tetravalent conjugate vaccine

licensed in 2005 for use in persons 9 months to 55 years old; 2 doses

● subgroups of bacteria
● age groups of patients
● geographical location

Factors Affecting Disease Patterns Worldwide

USA

○ Big outbreak due to serogroup A occurred during the earlier part of the 20th century but disappeared already
○ Most of the outbreaks are caused by serogroups C, Y, and B

Europe

○ Attack rates (more than 2/100,000 annually) is greaterthan in USA
○ Outbreaks mostly caused by serogroup B (vaccine for serogroup C was introduced)

Africa

○ Known as “meningitis belt” (sub-Saharan region from Ethiopia to Senegal)
○ Occurs during the dry season (opposite of what occurs in developed countries wherein cases are reported during the winter season)
○ 20 - 1,000 reported cases annually

Latin America

○ Varied epidemiological data according to countries
○ Most cases are caused by serogroups B and C
○ Emerging infections caused by serogroups W-135 and Y

Asia

Big outbreaks in China, Nepal, India and Russia caused by serogroup A

Serogroups B and C

dominant in Australia and Asia

Anton Weichselbaum

● Austrian biologist and pathologist
● First isolated the causative agent (Diplococcus intracellularis meningitidis), now known as Neisseria meningitidis or cerebrospinal meningitis in 1887.

LEPTOSPIRA SPP.

● Gram-negative but cannot be seen using Gram stain
● Spiral-shaped bacteria
● 2 flagella (corkscrew movement)
● Double hooked ends

Ubiquitous

LEPTOSPIRA SPP. is —- in the environment

False

TRUE OR FALSE. Leptospira spp. can be seen in an ordinary brightfield microscope.

LEPTOSPIRA SPP.

● Easily destroyed by heat, acids, alcohol

● Does not like salty environments

28-30°C

LEPTOSPIRA SPP. optimal growth temperature

Saprophytic Leptospira spp.

○ Ubiquitous in the environment
○ Does not cause disease in humans and animals (non-pathogenic)

Leptospira biflexa, L. meyeri

Saprophytic Leptospira spp. examples

Pathogenic Leptospira spp.

○ Causes illness in humans and animals
○ May also cause death

L. interrogans, L. borgpetersenii, L. kirschneri

Pathogenic Leptospira spp. examples

DNA relatedness

The old classification of leptospira was based on —-

L. interrogans sensu lato
L. biflexa sensu lato

Old classification of genus Leptospira divided into two:

pathogenic species

L. interrogans sensu lato

saprophytic/non-pathogenic species

L. biflexa sensu lato

30°C

L. interrogans sensu lato (pathogenic) optimal growth temp.

13°C

L. biflexa sensu lato (saprophytic) optimal growth temp.

negative

L. interrogans sensu lato (pathogenic) Growth in media with 8-azaguanine

positive

L. biflexa sensu lato(saprophytic) Growth in media with 8-azaguanine

negative

L. interrogans sensu lato (pathogenic) Spherical forms in 1M NaCl

positive

L. biflexasensu lato(saprophytic) Spherical forms in 1M NaCl

positive

L. interrogans sensu lato (pathogenic) Pathogenicity in susceptible animals (i.e., hamsters)

negative

L. biflexa sensu lato (saprophytic) Pathogenicity in susceptible animals (i.e., hamsters)

Contact with urine of infected animals

Transmission of leptospira spp.

True

TRUE OR FALSE. You can still get leptospirosis with intact skin.

Rodents leptospirosis

● Do not get sick nor die from infection
● Chronically infected (shed leptospires into their urine)

Dogs leptospirosis

● Fever
● Weakness
● Jaundice
● Vomiting
● Sometimes death

Swines leptospirosis

● Abortion during the 3rd week of pregnancy

Cattle leptospirosis

● Fever
● Depression
● Yellowish milk
● Decreased reproductivity
● Stillbirths or abortions (especially during late pregnancy)
● Death of calves

Horses leptospirosis

● Slight fever
● Mild anorexia
● Uveitis or moon blindness

Anicteric leptospirosis

● Mild form
● Fever
● Chills
● Severe headache
● Nausea
● Muscle pain
● Vomiting
● Abdominal pain
● Self-limiting

Icteric or Weil’s diseases leptospirosis

● Severe form of leptospirosis
● Triad of infection: jaundice, renal failure, hemorrhage
● May cause death

● Clinical manifestations
● Epidemiological information
● Laboratory tests

Diagnosis of leptospirosis

Microscopic agglutination test (MAT)

Reference test of serodiagnosis of leptospirosis

IgM and IgG

Microscopic agglutination test (MAT) antibodies detected

● Microscopic agglutination test (MAT)
● Enzyme-linked Immunosorbent Assay (ELISA)
● IFA
● Western blot

Serodiagnosis of leptospirosis

○ Vitamin B1 and B12 and long chain fatty acids (C>15)
○ Rabbit serum
Serum albumin

Cultivation of leptospira growth requirements

Importance of isolation

■ Definitive proof of infection
■ Determine prevailing serotype in a certain area
■ Prevention and control of leptospirosis (vaccine development)

Leptospira is isolated

Gold Standard:

MILD

Acute febrile illness
Stable vital signs
Anicteric sclerae
With good urine output
NO evidence of meningismus/meningeal irritation

MODERATE-SEVERE

Acute febrile illness
Unstable vital signs
Jaundice/icteric sclerae
Abdominal pain
Nausea, vomiting, and diarrhea
Oliguria/anuria
Meningismus/meningeal irritation
Sepsis/septic shock
Altered mental states
Difficulty of breath
Hemoptysis

Doxycycline 100mg 2x/day

First line agent for mild leptospirosis

Penicillin G 1.5 mu every 6-8 hrs

First line agent for moderate-severe leptospirosis