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MENINOGOCOCCAL DISEASE
Rabeen Lutchman
FCPAED PART 2 – MARCH 2013John, an eight year old boy, presents to you with a
one day history of severe headache and fever. He has vomited once. On examination there are signs of meningeal irritation, a decreased level of consciousness as well as a few petechiae on his conjunctivae. You suspect meningococcal meningitis.
1) Give a brief description of the causative organism.
2) Describe the pathogenesis of the disease.
3) Which Serogroups commonly cause disease in South Africa?
4) During which time of the year do you expect to find an increase in cases in South Africa?
5) Which laboratory investigations will you request and what results do you expect?
6) Discuss the initial management of the patient
QUESTION CONT…John’s pregnant mother is concerned about
herself and her younger daughter of 4 years old and enquires about chemoprophylaxis
1) To whom should chemoprophylaxis be given?2) For how long after the index case
identification will chemoprophylaxis still be beneficial
3) Which drugs can be used for chemoprophylaxis for the contacts in this case
4) Should John receive antibiotics to eradicate meningococcal carriage?
QUESTION CONT…The infection sister asks you whether
contacts can be immunized to prevent disease
1) Discuss the use of immunization to prevent disease in contacts
2) Which different types of vaccines are available against meningococcal disease?
3) Against which common Serogroup is a vaccine not commercially available?
GIVE A BRIEF DESCRIPTION OF THE CAUSATIVE ORGANISM.
Neisseria meningitidis is a gram-negative diplococcus.
Kidney-shaped pairs Humans only natural reservoir Commensal colonizers of the nasopharynx The meningococcal cell : lipid A–
containing lipo-oligosaccharides (LOS), including endotoxin, which is covered by a polysaccharide capsule
13 Serogroups Serogroups A, B, C, W135, and Y
DESCRIBE THE PATHOGENESIS OF THE DISEASE.
Droplet spread or intimate contact with nasopharyngeal secretions.
Nasopharyngeal colonization Asymptomatic carriage of meningococcus is an immunising
event and serum antibodies develops about 14 days after acquisition
Invasive disease - the organisms in the nasopharynx invade the epithelium and evade the immune system and result in septiceamia and dissemination
Type IV pili. Pili attach to CD46 proteins that serve as receptors for C3b,
C4b, measles, and other viruses on the epithelial cell surface. Endocytosis Serum antibodies Polysaccharide capsule - resist phagocytic killing. The virulence of meningococcus is related to the release of
lipopolysaccharide (endotoxin)
Risk Factors for acquiring invasive disease: The Agent- Certain strains are associated with invasive disease and have
acquired virulence factors
The Host- Medical conditions : Complement deficiency / Immune deficiency,
Functional or anatomical asplenia- Underlying chronic diseases,
The Environment- Nature and duration of contact- Household contacts have 400- 800 fold increase risk- Overcrowding (Hostel/Barracks/Millitry)- Coexisting viral infection (especially Influenza)- Exposure to tobacco (passive and active)- Low socioeconomic status are associated with higher risk
WHICH SEROGROUPS COMMONLY CAUSE DISEASE IN SOUTH AFRICA?
The meningococcal cell wall has lipid A–containing lipo-oligosaccharides (LOS), including endotoxin, which is covered by a polysaccharide capsule.
6 Serogroups A, B, C, W135, X and Y
These 6 Serogroups have geographic and time differences in distribution
WORLDWIDE
SOUTH AFRICANumber Of laboratory-confirmed meningococcal disease cases reported until the end of week 9, 2012 and 2013, by province
Province 2012 2013
Eastern Cape 8 9
Free State 0 3
Gauteng 22 10
KwaZulu-Natal 8 8
Limpopo 1 1
Mpumalanga 1 1
Northern Cape 0 1
North West 2 1
Western Cape 13 12
Total 55 46
SOUTH AFRICA SEROTYPES:
Serogroup data available for 25/46 (54%)Western Cape - Serogroup B predominanceGauteng / North West – Serogroup W135 Predominance
Percentage of Different Serogroups - National
Serogroup W135 - 48%Serogroup B -24%Serogroup Y- 16%Serogroup C -8%
DURING WHICH TIME OF THE YEAR DO YOU EXPECT TO FIND AN INCREASE IN CASES IN SOUTH AFRICA?
Occurs throughout the year but the incidence is highest in the late winter and early spring
Follows behind the Influenza season Numbers are expected to increase
during June and July, and to peak during the months of August to October
WHICH LABORATORY INVESTIGATIONS WILL YOU REQUEST AND WHAT RESULTS DO YOU EXPECT?
Try and add slide from medscape
?Clinical signs : Raised Intracranial Pressure
A Lumbar Puncture is NOT indicated in a child with meningococcaemia even if Meningism is found
A lumber puncture should never be done if there is any suggestion of impaired level of consciousness
A blood culture and urgent treatment based on clinical assessment
Non Culture Diagnostic Tests : Polysaccharide antigen testing PCR Skin Scrapings Post mortem specimens – in cases with
undiagnosed infection. Spleen/Heart blood cultures or post mortem CSF cultures
DISCUSS THE INITIAL MANAGEMENT OF THE PATIENT
Medical Emergency and Treatment should not be delayed
Early recognition : Nonspecific symptoms The classical, rapidly evolving purpuric rash associated with MD and
neck pain, or stiffness, usually develops after 12 h.Early recognition of shock: signs of hypoperfusion such as poor peripheral perfusion, impaired
level of consciousness, and reduced urine output should be evident.Fluid resuscitation: Initial emergency fluid resuscitation should include repeated boluses
of 20 mL/kg of isotonic crystalloid or colloids until shock has resolved.
May require even 100-200 mL/kg of fluid resuscitation (mostly those that need ventilatory support
There is a 94% rate of survival when shock is reversed within 75 minutes of presentation.
Fluid resuscitation more carefully if a child presents with signs of shock and hepatosplenomegaly or rales - myocardial dysfunction may be present.
Antibiotics: Antibiotic therapy - cornerstone of treatment. Should be initiated early Should not be delayed because of clinical
investigation. Choice determined by ability to penetrate CSF and
susceptibility of organism Recommended First line drug of choice for proven
meningococcal septicaemia or meningitis is IV benzyl penicillin for 5-7days
However Ceftriaxone or Cefotaxime should be used for emperic therapy for suspected meningitis
Those with a Beta-lactam allergy should receive Chloramphenicol.
Public Health Responsibility: IMMEDIATE telephonic notification followed by
written notification to the Department of Health
Isolation Identification of close contacts for all
confirmed and probable cases Provision of required post exposure prophlaxis
to close contacts Rapid investigation of the case Identification of other cases in the same
institute or community that may suggest a cluster
CHEMOPROPHYLAXISJohn’s pregnant mother is concerned about herself
and her younger daughter of 4 years old and enquires about chemoprophylaxis
To whom should chemoprophylaxis be given?= All CLOSE CONTACTS irrespective of vaccination
status Living/sleeping in the same household Pupils/students/military living in the same
dormitory Sharing a kitchen or same bathroom Any person who has been exposed to large
droplets or secretions from the respiratory tract- applies to health care staff/ambulance/emergency personnel
Where prophylaxis is NOT indicated: ALL the pupils in the classroom/creche ALL work/ school colleagues ALL Residents of the Hostel All individuals attending same social
function All passengers travelling in the same
plane, train, bus or car
FOR HOW LONG AFTER THE INDEX CASE IDENTIFICATION WILL CHEMOPROPHYLAXIS STILL BE BENEFICIAL
Prophylaxis should be given as early as possible (preferrable within 24hours)
It may still be effective if given up to 0 days after the presentation of the index case if delays are unavoidable
Overnight visitors to the home of the index case within 7 days before onset of illness should also receive prophylaxis
WHICH DRUGS CAN BE USED FOR CHEMOPROPHYLAXIS FOR THE CONTACTS IN THIS CASE
*Close contacts who are pregnant should receive Ceftriaxone 250mg IM
Name Dose (adults)
Dose (children)
Route Duration
Ciprofloxacin
500mg 10mg/kg PO Single dose
Ceftriaxone
250mg (<12years) 125mg
IM Single Dose
Rifampicin 10mg/kg bd
PO 2 days
SHOULD JOHN RECEIVE ANTIBIOTICS TO ERADICATE MENINGOCOCCAL CARRIAGE?
About 5-10 % people carry meningococci in the nasopharynx and very few will become ill depending on the risk factors previously mentioned
Carriage rates increase from about 2% in children about 5 to 25% in the late teens
Asymptomatic carriage is an immunising event and serum antibodies develops about 14 days after the acquisition of the meningococcus – it lasts for about 3 – 4 months and generates herd immunity
In households and closed populations the carriage rate is significantly higher
Nasopharyngeal carriers rather than patients with meningococcal disease are generally the source of new infections
IMMUNIZATIONSThe infection sister asks you whether contacts can be
immunized to prevent disease
Discuss the use of immunization to prevent disease in contacts (i.e post exposure vaccination)
Close contacts that HAVE BEEN GIVEN prophylaxis can LATER be offered the appropriate vaccine once the serotype has been confirmed
This extends period of protection Can be given up to 4 weeks after exposure and is
not an urgent procedure Use of the vaccine does NOT replace the immediate
need for prophylaxis (as the Serogroup is not known)
WHICH DIFFERENT TYPES OF VACCINES ARE AVAILABLE AGAINST MENINGOCOCCAL DISEASE?
3 Types of Vaccines available:
Polysaccharide Vaccines
Protein Conjugate Vaccines
Outer Membrane Vesicle(OMV)
Vaccine
Polysaccharide Vaccine Quadrivalent Vaccine available in SA (Serogroup A,C,
W135, Y) Bivalent Vaccine (A and C) also available Effective in controlling outbreaks Limitations:- Short duration of immune response (protection for
about 10-14 days after vaccination)- Serogroup A component is effective from 3 months of
age and last about 3 years but poorer protection for C, W135 and Y
- Low immunogenicity in children <2- Diminishes antibody responses after repeated
vaccinations against Serogroup C (hyporesponsiveness)
Protein Conjugate Vaccines: Tetanus Toxoid and CRM197 carrier proteins Immunogenic in all ages from > 2 months Available for single serotypes (C –MEN C, A) Induce immunologic memory - booster
response Prevent acquisition of carriage (MEN C used
in adolescent programs in Europe, Canada, Australia - decreased the incidence of MD)
Offers longer duration of protection than polysaccharide vaccines
Direct protection and herd immunity
OMV Vaccines : Serogroup B vaccine Have been effective in controlling
outbreaks or epidemics (Cuba/New Zealand/ Normandy)
Short duration of protection VERY strain specific – no cross
protection against strains that are not contained in the vaccine
Lack immunogenicity for infants
SOUTH AFRICA VACCINE POLICYPre exposure vaccination: Protect individuals at risk- Travellers to African Belt- Pilgrims to Saudi Arabia (at least 10 days
prior to arrival)- Persons with functional or anatomical
asplenia- Complement deficiencies- Lab staff in reference Labs routinely
working with the organism- ?1st year students moving into university
residences
AGAINST WHICH COMMON SEROGROUP IS A VACCINE NOT COMMERCIALLY AVAILABLE
The development of Vaccines against Serogroup B has many challenges
Serogroup B polysaccharide is poorly immunogenic (lacks immunogenicity) even when conjugated to a protein carrier
Outer membrane vaccines show some promise – but strain specific differences in the Outer membrane proteins suggest that these vaccines may still not provide protection against all Serogroup B meningococci
New Vaccines for Meningococcal Serogroup B disease:
Main problem is capsule not immunogenic and is associated with autoimmunity( similar to some embryonic neural tissue)
Therefore must use subcapsular antigens : OMV New protein recombinant vaccines are under trial
using ALL the subcapsular antigens, not only the OMV 2 vaccines are currently in phase 3 clinical trials One 4 component antigen vaccine has now being
licensed in the European Union – broader cover against different Serogroup B strains
Watch this space…
Thank You
REFERENCES