Micro - Meningococcal Diseases

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Meningococcal diseases -History - when was measles called the malignant purpuric fever?

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1805--"Malignant purpuric fever" in Geneva

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Meningococcal diseases - what did Anton Weichselbaum describe and when?

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1887--Anton Weichselbaum describes Diplococcus intracellularis meningitidis, isolated from CSF

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Meningococcal diseases -- When were the serogroups defined?

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World War I--many outbreaks, 4 serogroups defined (A-D)

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Meningococcal diseases -How and when did we get very low morbidity and mortality of measles?

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World War II--mass utilization of sulfadiazine resulted in very low morbidity/mortality

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Meningococcal diseases -Etiology - name and describe the measles organism

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Neisseria meningitidis--gram-negative diplococcus causing sepsis and meningitis

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Meningococcal diseases -Epi

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Infection limited to humans
Infection rate affected by overcrowding  
Seasonal occurrence: Increased incidence in spring (? associated with influenza season)
Dry season in Africa (sleeping indoors, lack of food, more personal contact)
Most common in children <15 years, males
Older age groups in epidemics
Epidemics in "meningitis belt" every 10 years;
attack rates up to 517/105 in Burkina Faso 1979
80-90% mortality in epidemic without antibiotics
Spread to medical personnel rare (except with mouth-to-mouth)

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Meningococcal diseases - who are the hosts?

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Infection limited to humans

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Meningococcal diseases -Epi - who mostly gets it?

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Most common in children <15 years, males
Older age groups in epidemics

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Meningococcal diseases -Epi
Epidemics in "____" every 10 years;

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Epidemics in "meningitis belt" every 10 years;attack rates up to 517/100,000 in Burkina Faso 1979

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Meningococcal diseases -Epi
__% mortality in epidemic without antibiotics

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80-90% mortality in epidemic without antibiotics

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Meningitis Transmission

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Respiratory spread from cases or asymptomatic carriers (mostly latter)
Secondary attack rate 2-4/1000 (1000 x > U.S. population rate); often co-primary cases presenting within 96 hrs. of first case
Carrier rate increases with age (0.5-1% in 3- 48 mo., 20-40% young adults); chronic carriage lasts for weeks

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Meningitis Transmission-
Carrier rate ___with age ; chronic carriage lasts ___

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Carrier rate increases with age (0.5-1% in 3- 48 mo., 20-40% young adults); chronic carriage lasts for weeks

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Meningitis Transmission - Secondary attack rate 2-4/1000 (1000 x > U.S. population rate); often ___ cases presenting within __hrs. of first case

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Secondary attack rate 2-4/1000 (1000 x > U.S. population rate); often co-primary cases presenting within 96 hrs. of first case

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Meningitis PATHOPHYSIOLOGY

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Bacteria have predilection for posterior pharynx
90% infections limited to posterior pharynx, with mild bacteremia
With blood invasion, a variety of manifestations from self-limiting bacteremia to overwhelming sepsis are seen
Clinical manifestations due to tissue injury from LPS (with increased blood-brain barrier permeability) and to secondary cytokine messengers (eg. TNF)
Fibrin thrombi and small vessel vasculitis produce necrosis

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Meningitis PATHOPHYSIOLOGY
Bacteria have predilection for ___

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Bacteria have predilection for posterior pharynx
90% infections limited to posterior pharynx, with mild bacteremia

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Meningitis PATHOPHYSIOLOGY
- Clinical manifestations due to

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Clinical manifestations due to tissue injury from LPS (with increased blood-brain barrier permeability) and to secondary cytokine messengers (eg. TNF)

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What produces necrosis?

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Fibrin thrombi and small vessel vasculitis produce necrosis

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Meningitis - DISEASE SPECTRUM

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A. MILD BACTEREMIA
B. MENINGITIS
C. MILD MENINGOCOCCEMIA
D. FULMINANT MENINGOCOCCEMIA
E. CHRONIC MENINGOCOCCEMIA

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MILD BACTEREMIA

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+/- Fever, arthralgias
Pink, rubella-like rash
Symptoms may regress for several days only to be followed by severe disease
Less virulent forms localize: meningitis
epididymitis
arthritis
pneumonitis
conjunctivitis
myocarditis

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In Mild Bacteremia, where do the less virulent forms localize?

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Less virulent forms localize: meningitis
epididymitis
arthritis
pneumonitis
conjunctivitis
myocarditis

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Describe MENINGITIS

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MENINGITIS
 
Most common between ages 3 months-15 years, 30-40% of cases are bacteremic
Myalgias more common than other meningitides
Petechial rash may suggest etiology (Differential diagnosis: Staph endocarditis, RMSF, dengue hemorrhagic fever, TTP)
Focal cerebral findings, cerebral edema—these are reversible with prompt antibiotics
Association later deafness

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Describe MENINGITIS
Most common between ages __, 30-40% of cases are __

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Most common between ages 3 months-15 years, 30-40% of cases are bacteremic

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Describe MENINGITIS
What is the most common symptom compared to other meningitides?

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Myalgias more common than other meningitides

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Describe MENINGITIS
What may suggest etiology?

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Petechial rash may suggest etiology

(Differential diagnosis: Staph endocarditis, RMSF, dengue hemorrhagic fever, TTP

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Describe MENINGITIS
- is assocated with what?

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Association later deafness

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Describe MILD MENINGOCOCCEMIA

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MILD MENINGOCOCCEMIA
 
Most common presentation

Petechial rash and fever

May resolve in 2-3 days with retrospective blood culture diagnosis only OR:

Progress to petechiae, ecchymoses, hypotension, shock OR:

Initial symptoms may persist for one week, followed by joint effusions

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Describe MILD MENINGOCOCCEMIA - what is the most common presentation?

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MILD MENINGOCOCCEMIA
 
Most common presentation
Petechial rash and fever

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Describe MILD MENINGOCOCCEMIA - May resolve in 2-3 days with retrospective blood culture diagnosis only OR:

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Progress to petechiae, ecchymoses, hypotension, shock OR:

Initial symptoms may persist for one week, followed by joint effusions

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FULMINANT MENINGOCOCCEMIA - Describe

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10% of clinical disease
Petechiae in crops coalesce into purpura
High fever, dizziness, rigors, weakness, hypotension, shock, disseminated intravascular coagulation (DIC) are common
Poor prognostic signs: Petechiae <12 hrs. prior to hospitalization Leukopenia Absence of meningitis
Thrombocytopenia
Shock
Extremes of age
Temperature > 40oC

Group A strep, gram-negative, Staphylococcal sepsis may mimic symptoms

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FULMINANT MENINGOCOCCEMIA - Describe the petechiae

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Petechiae in crops coalesce into purpura

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FULMINANT MENINGOCOCCEMIA - What are the common symptoms?

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High fever, dizziness, rigors, weakness, hypotension, shock, disseminated intravascular coagulation (DIC) are common

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FULMINANT MENINGOCOCCEMIA - What are the poor prognostic signs?

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Poor prognostic signs: Petechiae <12 hrs. prior to hospitalization Leukopenia Absence of meningitis
Thrombocytopenia
Shock
Extremes of age
Temperature > 40oC

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FULMINANT MENINGOCOCCEMIA - What may mimic the symptoms?

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Group A strep, gram-negative, Staphylococcal sepsis may mimic symptoms

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Describe CHRONIC MENINGOCOCCEMIA

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CHRONIC MENINGOCOCCEMIA
 
Intermittent febrile periods of 1-6 days over weeks, rare presentation
20% develop splenomegaly and meningitis
Migratory arthralgias, polymorphous rash
Blood culture positive with fever only

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CHRONIC MENINGOCOCCEMIA - what do 20% develop?

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20% develop splenomegaly and meningitis

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CHRONIC MENINGOCOCCEMIA
- when is the blood culture positive?

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Blood culture positive with fever only

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CHRONIC MENINGOCOCCEMIA - what is the fever pattern?

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Intermittent febrile periods of 1-6 days over weeks, rare presentation

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CHRONIC MENINGOCOCCEMIA - what are the common symptoms?

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Intermittent febrile periods of 1-6 days over weeks,
Migratory arthralgias,
polymorphous rash

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Diagnosis of Meningitis

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Blood culture (50-75% + in meningococcemia)
Spinal tap (LP) if signs of meningitis present--Gram's stain, culture
Gram's + in 80% CSF if untreated--BEST TEST
Group A & C show capsules, Quellung test
Culture on Thayer Martin or chocolate agar
at increased CO2 pressure
Other tests—Gram st./culture buffy coat or petechiae
Latex agglutination, ELISA

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What is the best test for meningitis?

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Gram's + in 80% CSF if untreated--BEST TEST

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What groups show capsules on the quellung test?

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Group A & C show capsules, Quellung test

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what culture medias do you use?

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Culture on Thayer Martin or chocolate agar at increased CO2 pressure

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Describe the quellung test

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Neufeld capsular swellingNeu·feld capsular swelling (noi'fělt)n.An increase in the opacity and visibility of the capsule of encapsulated organisms resulting from exposure to specific, agglutinating, anticapsular antibodies. Also called Neufeld reaction, quellung phenomenon, quellung test.

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What is the treatment of meningitis?

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MEDICAL EMERGENCY - IMMEDIATE Abx and isolation
 
1) Respiratory ISOLATION for 24 hrs. after starting treatment
2) Cefotaxime, ceftriaxone--usual initial treatment pending culture result and beta lactamase testing
3) High dose IV penicillin or ampicillin x 7 days after confirmation of etiology and confirmation of negative beta lactamase test

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Supportive measures

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Supportive measures:
Maintain oxygenation
Reverse acidosis
Maintain intravascular volume
Maintain blood pressure (dopamine)
Correct CHF (diuretics)
Control seizures
ROIDS!!! - Dexamethasone 0.6 mg/kg IV divided q6 x 4 days with meningitis for cerebral edema, to reduce risk of deafness!!!!

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How do you get immunity to meningitis?

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Group-specific; acquired by infection OR carriage within 5-12 days
Bacteriocidal antibody is protective
Group A, C antibodies acquired by placental transfer
Group B polysaccharide is similar to human glycoproteins, produces immunologic tolerance and group B outbreaks in newborns
Complement deficiency and splenectomy are associated with chronic meningococcemia and higher risk of infection

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____ antibody is protective

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Bacteriocidal antibody is protective

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____ acquired by placental transfer

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Group A, C antibodies acquired by placental transfer

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___ is similar to human ____, produces immunologic ____and group B outbreaks in newborns

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Group B polysaccharide is similar to human glycoproteins, produces immunologic tolerance and group B outbreaks in newborns

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_____ are associated with chronic meningococcemia and higher risk of infection

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Complement deficiency and splenectomy are associated with chronic meningococcemia and higher risk of infection

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CONTROL/PREVENTION

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Immunize with vaccine (if vaccine serogroup is causing the outbreak)
Rifampin prophylaxis--commonly used now due to sulfa resistance
Adults 600 mg bid x 2 days, child. 10 mg/kg/dose x 4
Problems of rifampin: Up to 25% resistant
Does not treat
Transient, 80% eradication
Ceftriaxone, ciprofloxacin (adults only) have also been used for prophylaxis

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what is used for prophylaxis and why?

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Rifampin prophylaxis--commonly used now due to sulfa resistance

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Problems of rifampin

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Up to 25% resistant
Does not treat
Transient, 80% eradication

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MENINGOCOCCAL VACCINE -
Polysaccharide vaccine contains serogroups ____;
bivalent __and trivalent __also used in Africa

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Polysaccharide vaccine contains serogroups A, C, Y, W135; bivalent AC and trivalent A-C-W135 also used in Africa

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MENINGOCOCCAL VACCINE
African outbreaks due to serogroups __ until after 2000, when ___ first noted in epidemics

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African outbreaks due to serogroups A and C until after 2000, when X and W135 first noted in epidemics

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MENINGOCOCCAL VACCINE -
Polysaccharide vaccine (1981) effective age ___; ___ effective for > 1 year

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Polysaccharide vaccine (1981) effective age > 2 yrs; 90% effective for > 1 year

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MENINGOCOCCAL VACCINE - how many doses and S/Es

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Single dose; local erythema and soreness only

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__ vaccine licensed in 2005; now recommended in US for ___, and for all children ages ___

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Conjugate vaccine licensed in 2005; now recommended in US for hi risk ages 2 and older, and for all children ages 11 and older

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MENINGOCOCCAL VACCINE - Indications

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Complement/properdin deficiency
Asplenia, sickle cell disease
Travel to endemic area
Contact of primary case
Outbreaks due to included serotypes

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MENINGOCOCCAL VACCINE - what limits it's usefullness?

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Short term immunity limits usefulness of vaccinations

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MENINGOCOCCAL VACCINE
Northern Nigeria 1978-81: 7.4 million vaccinated, eliminated epidemics of ___

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Northern Nigeria 1978-81: 7.4 million vaccinated, eliminated epidemics of serogroup C

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MENINGOCOCCAL VACCINE - Brazil early 1970s: country-wide immunization with ___ vaccine was effective in controlling epidemics

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Brazil early 1970s: country-wide immunization with bivalent AC vaccine was effective in controlling epidemics

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New initiatives using ____ may provide better long term protection

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New initiatives using conjugate vaccines may provide better long term protection

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Meningiococcal Diseases in 2010

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Devastating epidemics will continue to occur in countries throughout the meningitis belt of Africa
Emergence of epidemics due to a newer serogroup (W-135) in Africa
In the United States, increased frequency of outbreaks and changes distribution of serogroups responsible for endemic disease (increase in cases due to serogroup Y) as well as increased disease among adolescents and young adults.