Meningococcal infection

1. W. P. Rivindu H. Wickramanayake
Group no. 04a
6th Year 2nd Semester – 2020 September
Tbilisi State Medical University, Georgia
Meningococcal Infection

2. Introduction
● One of the most serious and life-threatening infectious diseases during childhood is bacteremia, a consequence of
which is septic shock, where inadequate perfusion of tissues occurs due to endotoxemia.
● Neisseria meningitidis (Meningococcus) is an important bacterial infection manifesting as meningitis or
septicemia, or more often a combination of both.
● Asymptomatic pharyngeal colonization is the initial step of infection, with humans being the natural reservoirs.
● From the nasopharynx, the coccus reaches the meninges translocating across the nasopharyngeal mucosa and
along the perineural sheath of the olfactory nerve, through the cribriform plate of the ethmoid.
● Bloodstream spread to the meninges will cause meningitis.
● In some children, the predominant feature is cardiovascular collapse leading to septic shock.
● Transmission occurs by respiratory droplets and requires close direct contact.
● Children younger than 5 years do not have adequate immunity against the polysaccharide antigens of N.
meningitidis.
● The risk factors for infectious disease in child care facilities include immunologic susceptibility, lack of
awareness, and practice of good hygiene, a natural tendency to intimacy, frequent oral contact with objects in the
environment.
● The invasive meningococcal disease is seen in 2 age groups: infants who are vulnerable due to disappearance
in the early life of the maternal antibodies & adolescents with a high rate of colonization of nasopharynx.

3. Etiology
● N. meningitidis is a gram-negative coccus in pairs with adjacent sides flattened. It is non-motile, aerobic, and
facultatively anaerobic. It produces catalase and is oxidase positive. It produces acid from glucose and maltose.
Fresh isolates require enriched media like blood or chocolate agar. Incubation in a humidified 10% carbon
dioxide (CO2) environment enhances growth.
Virulence factors include the polysaccharide capsule, which enhances invasiveness by inhibiting phagocytosis and
enhancing organism survival during the bloodstream and central nervous system (CNS) invasion. Pili mediate
attachment, colonization, and invasion of the organisms to the mucosal cells of the nasopharynx. The antigenic
variation of pili by a cassette mechanism allows the bacterium to escape the host's immune system.
Outer Membrane Proteins
Porin proteins can insert themselves into membranes of target cells, and phagolysosomes can induce apoptosis. OPC
protein functions in mucosal adherence and invasion of endothelial cells. IgA1 protease hydrolyzes IgA1 molecules
in the hinge regions. The enzyme inactivates IgA1 at mucosal surfaces, enabling initial attachment and subsequent
invasion. Pathogenic Neisseria survives and multiplies by their ability to extract iron from high-affinity iron-binding
proteins. N. meningitidis can acquire penicillin resistance from commensal Neisseria species in the nasopharynx
through DNA fragments by the transformation. Meningococcus also exhibits a phase variation of surface antigens,
thus evading the host immune response.
The capsular polysaccharides are antigenic and form the basis of serogroups. Twelve serogroups are A, B, C, H, I, K,
L, X, Y, Z, W-135, and 29F. Serogroups A, B, C, W-135, X, and Y are the most common causes of invasive disease
worldwide.

4. Epidemiology
● In developing countries, the incidence rate is 10 to 25 per 100,000 inhabitants per year.
● The highest rate of 10 to 1000 per 100,000 per year is seen in a belt across sub-Saharan Africa, termed
the meningitis belt, with recurrent epidemics of group A.
● Death occurs in 6% to 10% of cases and complications in 4.3 to 11.2% of cases.
● Group A was predominant from 2007 through 2009, while serogroup W135 predominated in 2010
through 2011.
● In 2013 and 2014, 2 outbreaks of meningococcal serogroup C, a strain relatively rare in
Africa, occurred in Nigeria and Kebbi.
● International outbreaks of N. meningitidis infections occurred in 1987 and 2000 associated with the
Hajj pilgrimage to Mecca.
● 1987 outbreak was due to serogroup A and the 2000 outbreak due to serogroup W-135. Serogroup W
has emerged in other regions, including South America and England.
● In European countries, invasive serogroup C disease has declined, and serogroup B is causing 60% to
72% of cases of invasive disease.
● In Asia, large epidemics caused by serogroup A occurred historically in China, India, Nepal, and
Russia. More recently, serogroup B and C emerged as the cause in this area.
● An increase in the serogroup Y has been reported in the Nordic European countries.

5. Pathophysiology
● Primary cause of cardiovascular collapse from sepsis is a peripheral circulatory failure.
● Cardiac dysfunction due to myocardial failure plays a prominent role.
● Higher endotoxin (LOS) concentrations were associated with shock, renal failure, and
respiratory distress.
● High concentrations of IL-6 and IL-8 are seen in those with meningococcal shock.
● TNF and IL-1 activate endothelial cells by increasing their permeability and
adhesiveness for white cells.
● Overproduction of nitric oxide lowers arterial pressure due to vasodilation. It also
impairs cardiac contractility.
● Endothelial cell retraction on interaction with bacterial endothelial cells leads to a loss of
integrity, causing capillary hemorrhages and the formation of thrombi in purpuric
lesions.
● When a large number of bacteria colonize the blood vessels and leads to the
corresponding signaling, this is responsible for the extensive purpuric lesions and
severity of shock in Purpura fulminans.

6. ● Histology of skin lesions shows endothelial necrosis of
capillaries and small veins in the dermis and subcutaneous tissue.
● Neutrophil infiltration and occlusion of vessels with WBCs,
platelets, fibrin thrombi, and hemorrhage are seen.
● Meningococci are seen within the endothelium and thrombi.
Histopathology

7. ● The disease spectrum caused by N. meningitidis ranges from asymptomatic
carriage to death due to fulminant meningococcemia.
● Meningococcal meningitis and septicemia are the common syndromes
reported, although both clinical pictures present in some cases.
● The signs and symptoms of meningococcemia include an early upper
respiratory tract infection with coryza, pharyngitis, tonsillitis, and
laryngitis.
● Patients are febrile with a headache, vomiting, and lethargy.
● Typically, patients with meningococcemia have a fever and hemorrhagic
rash, followed by signs of severe circulatory collapse.
● Purpura and shock often develop within hours.
● Diffuse mottling to extensive purpuric lesions are the skin manifestations.
● Petechiae or purpura are seen in 50% to 60% of patients.
● Twenty percent to 30% of children may not have a rash on presentation.
History and Physical

8. ● Chronic meningococcemia is defined as meningococcal septicemia with fever
for at least a week before antibiotic therapy and with no meningeal symptoms.
● In chronic meningococcemia, bacteria are never found by biopsy or culture of
skin lesions.
● Researchers postulate that the skin changes and arthritis may result from
antigen-antibody complexes.
● The diagnosis is established by identifying the organism in blood cultures.
● Recovery is prompt following antibiotic therapy.
● Myocardial manifestations associated with meningococcal meningitis, including
heart failure with pulmonary edema and high central venous pressures
accompanying signs of poor peripheral perfusion.
● Treatment of myocardial failure can ameliorate the situation.
● Increased levels of interleukin 6 may be a mediator of myocardial depression in
septic shock due to meningococcal infection.
Continued;

9. ● Diagnosis should be clinically made, and broad-spectrum antibiotic therapy started with pending
organism identification.
Microbiological Diagnosis
- Public health control
- Antibiotic sensitivity
- To exclude other organisms
Gram Stain
- Cerebrospinal fluid (CSF) in meningitis shows gram-negative intracellular and
extracellular diplococci.
- Skin lesions in meningococcemia: Needle aspiration and scrapings are Gram-stained
Buffy coat of blood Gram stain
Culture - CSF is inoculated onto chocolate agar and incubated in 3% to 5% CO2
- Specimens from mucosa are inoculated into selective medium- Thayer-Martin chocolate
agar to which vancomycin, colistin, and nystatin are added to inhibit commensals.
- Blood culture: 40% to 75% positive before starting treatment. CSF cultures are positive in
90% of untreated patients with meningitis
- Combining the results of blood & CSF cultures with CSF Gram stain identifies 94% of
meningitis antigen.
Evaluation

10. Antigen Detection
- The meningococcal antigen in CSF (serum and urine have cross-reactions): Latex
agglutination; Poor sensitivity and specificity for capsular B type
- PCR assays can detect meningococcal DNA in CSF, plasma, and serum. Sensitivity and
specificity are above 90%. It is more sensitive than blood culture. Diagnosis can be made in 4
to 8 hours. PCR assays are less affected by previous antibiotic therapy.
Imaging
- If the patient is in a coma, computed tomography (CT) brain imaging is helpful to
exclude intracranial hemorrhage.
Hematologic and Metabolic Abnormalities
- In meningococcal meningitis, CSF, WBC count, peripheral blood leukocyte count
and C-reactive protein, procalcitonin, and ESR are elevated. CSF has raised protein, low
glucose, and gram-negative Diplococcus.
- In meningococcal septicemia, metabolic derangements like hypoglycemia,
hypokalemia, hypocalcemia, hypomagnesemia, hypophosphatemia, and metabolic acidosis
are seen in severe cases. Anemia, coagulopathy, decreased protein C, fibrinogen, prothrombin,
and coagulation factors (V, VII, and X) are also seen.
Continued;

11. Antimicrobial Agents
- Third-generation cephalosporin-ceftriaxone or cefotaxime are used for
initial therapy.
Continued disease:
• Ceftriaxone (80 mg/kg per day in 1 to 2 divided doses intravenously [IV])
• Cefotaxime (200 mg/kg per day in 3 to4 divided doses IV)
• Penicillin G (50 mg/kg every 4 to 6 hours IV)
• Chloramphenicol (100 mg/kg/day in 4 divided doses, orally or IV)
• Meropenem for those with severe allergies
- The recommended duration of therapy is 7 days for both meningitis and
meningococcemia.
Treatment / Management

12. Adjunctive and Experimental Therapies
- Corticosteroid therapy: Replacement doses (25 mg/m3 hydrocortisone
4 times) daily is useful in children with refractory shock associated with impaired
adrenal gland response.
• Recombinant bactericidal permeability-increasing protein (rBPI)
binds to endotoxin and blocks the inflammatory cascade. Children
receiving rBPI had fewer amputation and blood product transfusions and
improved functional outcomes.
• Other adjunctive therapies in the management of septicemia are
plasmapheresis, extracorporeal membrane oxygenation (ECMO),
fibrinolysis, and anti-mediator therapy.
Continued;

13. Emergency Management
• After securing the airway, priorities in children with meningococcal disease
are:Correction of cardiovascular shock and
• Control of raised intracranial pressure
• Aggressive fluid resuscitation with 0.9% NaCl solution in a volume of 20
ml/kg over 5 to 10 minutes is of importance and repeated until shock
improves. Inotropic support is needed to maintain tissue perfusion.
• Human albumin solution can be used as an alternative.
• Anemia, coagulopathy is monitored and corrected.
• In cases of raised intracranial pressure, adequate cerebral perfusion should
be ensured by correcting shock and providing neurointensive care.
Continued;

14. Infectious
1. Rocky Mountain spotted fever
2. Ehrlichiosis
3. Streptococcal pneumoniae
4. Hemophilus influenza type B
5. Group A streptococcus
6. Staphylococcus aureus
7. Gram-negative bacterial sepsis
with DIC
8. Infective endocarditis
9. Gonococcemia
10. Rat-bite fever
11. Typhus
12. Secondary syphilis
Non-Infectious
1. Henoch-Schonlein purpura
2. Acute hemorrhagic edema of infancy
3. Platelet disorders (Idiopathic
thrombocytopenic purpura)
4. Collagen vascular disease
5. Neoplastic processes
Differential Diagnosis

15. ● Scoring systems are devised to predict prognosis with meningococcal
disease. Most prognostic scoring systems agree that purpura fulminans
and shock are poor prognostic signs.
● The Glasgow meningococcal septicemia prognostic score (GMSPS)
evaluates 7 key items: hypotension, the difference in skin-core
temperature, coma, acute deterioration, the absence of meningismus,
progressive purpura, and base deficit.
● At Los Angeles Children's Hospital, 5 features were correlated with a poor
prognosis: Shock or seizures, hypothermia, total WBC count less than
5000/mm, platelet count less than 100,000/mm, and development
of Purpura fulminans.
● The overall mortality of invasive meningococcal disease is 7% to 19%.
Prognosis

16. ● Sequelae of meningococcemia are skin necrosis (ischaemic
infarction of skin and soft tissues), hearing loss, deafness,
seizure, amputation, and skin scarring.
● Impaired organ perfusion due to hypovolemia, vasoconstriction,
and myocardial failure result in prerenal failure manifesting as
oliguria or anuria or acute tubular necrosis.
● Immunologic or reactive complications like arthritis, cutaneous
vasculitis, iritis, and pericarditis are due to the deposition of
immune complexes with polysaccharide antigen, IgG, and C3
resulting in acute inflammation.
Complications

17. Vaccine Prevention
● Monovalent capsular group C meningococcal conjugate vaccines (MenC) are used in
Europe, Australia, and Canada for routine immunization of infants and toddlers. They
are highly effective, although a booster at adolescence is advocated.
● Quadrivalent meningococcal A, C, Y, W conjugate vaccines (Men ACYW) are used for
adolescent immunization in North America. It is being used as a vaccine for high-risk
groups and travelers in many countries. It is also replacing Men C as an adolescent
booster outside the United States.
● Booster doses of Men ACYW are advocated in the United States for high-risk children
and persons immunized at younger than 15 years of age. Capsular group B outer
membrane vesicle (OMV) vaccines are used for outbreaks involving single clones.
● Two capsular group B vaccines (Men B-4C, 2 doses, and Men B-FHbp, 3 doses) are
licensed for people older than 10 years of age. It is recommended for at-risk patients
and outbreaks and can be given at 16 to 23 years of age at clinical discretion.
Prophylaxis/Prevention

18. Chemoprophylaxis for Contacts of Patients of Meningococcal Disease
Antibiotic Dose
● Rifampin: 10 mg/kg per dose; Orally every 12 hours for 4 doses (for
infants younger than 1 month of age, 5 mg/kg per dose)
● Ceftriaxone: Single injection of 125 mg for less than 15 years and 250 mg
for older than 15 years*
● Ciprofloxacin: 20 mg/kg (max 500 mg) older than 1 month of age*
* From American Academy of Pediatrics Committee on Infectious Diseases. Red book
2015 Report of the Committee on Infectious Diseases, 30th edition. Elk Grove, IL,
American Academy of Pediatrics 2015.

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