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