Meningococcus has a polysaccharide capsule on the basis of which thirteen serogroups have been identified. Five common serogroups (A, B, C, Y and W135) are responsible for about 90% of infections caused by N. meningitidis. Recently serotype X has been identified in some outbreaks and presently we do not have any vaccine for this serotype ( WHO Position paper 2011) . S erogroups A, B and C account for most cases of meningococcal disease throughout the world, with serogroups A and C predominating throughout Asia and Africa and serogroups B and C responsible for the majority of cases in Europe and the Americas. In 2000, an international outbreak among pilgrims returning from the hajj (the pilgrimage to Mecca) and their close contacts, including four persons from the United States, was due to serogroup W135. Recently, serogroup W135 has been associated with an outbreak amongst Hajj pilgrims as well as a large epidemic in Burkina Faso during 2002 and 2003. Globally more than 50% of meningococcal disease in infants under the age of 1 year is attributed to serogroup B against which no vaccine is available. A and C are seen in the epidemic form in India. Endemic disease is usually by serotype B or at times by Y,W135 .
Correct answer: D. Sporadic with outbreaks Meningococcal disease occurs only sporadically in India, and endemic disease is caused mostly due to serogroups A, B and C. Repeated outbreaks have been reported all over the country mostly due to serogroup A in Surat, Gujarat(1985-87) and areas adjoining Delhi (1966-1985). The latest outbreak in Delhi in 2005 was due to serogroup A and caused several fatalities.
Meningococcal Polysaccharide vaccine: Bivalent (A+C) and Quadrivalent (A,C,Y,W135) are indicated for adults and children older than 2 years and under special circumstances in children three months to two years of age. The antibody responses to each of the four polysaccharides in the quadrivalent vaccine are serogroup-specific and independent. Protective antibody levels are usually achieved within 7-10 days of vaccination. The serogroup A polysaccharide induces antibody in some children as young as three months of age, although a response comparable with that occurring in adults is not achieved until age 4-5 years. The serogroup C component is poorly immunogenic in children less than 2 years. The serogroup A and C vaccines have good immunogenicity, with clinical efficacy rates of 85 percent or higher among children five years of age or older and adults. Serogroup Y and W-135 polysaccharides are safe and immunogenic in older children and adults; although clinical protection has not been documented. In infants and young children aged < 5 years, measurable levels of antibodies against serogroup A and C polysaccharides, as well as clinical efficacy, decrease substantially during the first three years after a single dose of the vaccine has been administered. Antibody levels also decrease in healthy adults, but antibodies are still detectable up to 10 years after immunization> Multiple doses of serogroup A and C polysaccharides may cause immunologic tolerance of the polysaccharides. Vaccines are safe and most common side effects are local pain and redness at site of injection. These "thymus-independent" vaccines do not induce immunological memory and the response in children younger than two years is poor. Meningococcal conjugated polysaccharide vaccine In the United Kingdom, serogroup C conjugate vaccines were added to the routine schedule of childhood immunizations in late 1999. A quadrivalent A, C, Y and W-135 conjugate vaccine has been licensed in United States in January 2005. It is speculated that ~70% of the disease in individuals older than 10 years would be vaccine preventable. This vaccine contains 4 µg each of A, C, Y and W-135 polysaccharide conjugated to 48 µg of diphtheria toxoid (Menactra; Aventis Pasteur). In Nov 2011 this vaccine has been approved by FDA for use in children as young as 9 months. A trial has been carried out with this vaccine in India in age group 2-55 years. Results in January 2012, yet to be published. Will be available in India after some time. These meningococcal conjugate vaccines induce a T-cell-dependent response, resulting in an improved immune response in infants, priming immunologic memory and leading to a booster response to subsequent doses. These vaccines provide long-lasting immunity even when given as a series in infancy and thus induce herd immunity through protection from nasopharyngeal carriage. These vaccines have been found safe, immunogenic and have acceptable reactogenicity in all ages. The conjugated polysaccharide vaccine is contraindicated in patients with a known hypersensitivity to any component of the vaccine.
The major drawback of the presently available vaccines is the absence of activity against group B meningococci, which is common serotype in some Western European countries. Since group B polysaccharide is a 200-residue (a2-8) homopolymer of N -acetylneuraminic acid (poly2-8NeuNAc) that mimics the human neuronal cell adhesion molecule, the use of group B capsule in a vaccine risks the induction of autoimmunity. In any case however, since the antibody response to the group B capsule is limited after natural infections, group B capsular polysaccharide is a poor candidate for vaccine development.
Only meningococcal polysaccharide vaccines are available in India at present. Routine immunization with the polysaccharide vaccines is indicated in the following children aged 2 years or more ( 3 months or older if risk of meningococcal disease is high). Dosage: children aged 2 years or more: A single dose 0.5 ml SC/ IM is recommended. In infants aged 3 months to 2 years 2 doses 3 months apart are recommended. The quadrivalent vaccine is particularly preferred for Haj pilgrims and travelers where W135 disease is documented. Revaccination with one more dose of the vaccine 2-5 years after the first dose may be considered in those children who are remain at high risk of infection or who have been vaccinated at age younger than 4 years The conjugate vaccines will be preferred over the polysaccharide vaccines once they are available in India.
The first step is to confirm that there is indeed an outbreak i.e the number of cases is more than the endemic rates. Western data indiacte that an attack rate of > 10 cases/ 100,000 population indicates an outbreak ( roughly 3 confirmed/ probable meningoccal cases of the same serogroup that occurred n the past 3 months that are not close contacts of each other). Mostly an outbreak is obvious. Vaccination with the serogroup specific vaccine (In India most outbreaks have been due to A and hence the bivalent vaccine may be used) should be given to all patients aged 2-29 years in the smallest geographical area that includes all the cases. Vaccines are not usually effective in those under 2 and in outbreaks disease mostly affects those under the age of 30. If the population is very large vaccination may be given to the age group with the highest attack rates. Mass chemoprophylaxis (i.e., administration of antibiotics to substantial populations) is not recommended to control large outbreaks of disease. Disadvantages of mass chemoprophylaxis include cost of the drug and administration, difficulty of ensuring simultaneous administration of drugs to substantial populations, drug side effects, and emergence of resistant organisms. In addition, multiple sources and prolonged risk for exposure make this approach impractical and unlikely to succeed. In the majority of outbreak settings, these disadvantages outweigh the possible benefit in disease prevention.
Yes. Close contacts of patients with meningococcal disease ( household contacts, day care contacts, HCW in contact with secretions A single dose 0.5 ml SC/ IM is recommended. In infants aged 3 months to 2 years 2 doses 3 months apart are recommended. Only meningococcal polysaccharide vaccines are available in India at present. Routine immunization with the polysaccharide vaccines is indicated in the following children aged 2 years or more ( 3 months or older if risk of meningococcal disease is high).
Protective antibodies appear within 10-14 days of vaccianation
Three characteristics of conjugate vaccines are believed to be important for establishing long-term protection against a bacterial pathogen: memory response, herd immunity, and circulating antibody. Recent data from the United Kingdom indicate that although vaccination primes the immune system, the memory response after exposure might not be rapid enough to protect against meningococcal disease. After initial priming with a serogroup C meningococcal conjugate vaccine, a memory response after a booster dose was not measurable until 5–7 days later. The incubation period for meningococcal disease usually is less than 3 days. In UK, to date no evidence of herd immunity has been observed Therefore, circulating bactericidal antibody is critical for protection against meningococcal disease. There is sufficient evidence to indicate that approximately 50% of persons vaccinated 5 years earlier had bactericidal antibody levels protective against meningococcal disease. Therefore, more than 50% of persons immunized at age 11 or 12 years might not be protected when they are at higher risk at ages 16 through 21 years. ACIP recommended revaccination with conjugated meningococcal vaccine in individual previously vaccinated with either conjugated or polysaccharide vaccine who are at increased risk for meningococcal disease. Those who are vaccinated at age greater than 7 years should be vaccinated 5 years after their previous meningococcal vaccine and those vaccinated at ages 2-6 years should be revaccinated 3 years after their previous meningococcal vaccine. Persons who remain in one of these increase risk group indefinitely should continue to be revaccinated at 5 year interval.
Very serious disease, may present it self in two deadly forms Meningitis (case fatality: 10-14 %) Septicaemia (case fatality: around 40 %) Long-term sequelae (10% 15%) Deafness Cranial nerve palsy Retardation Limb loss Symptoms are not diagnostic/pathognomic, often leading to misdiagnosis Can progress rapidly, sometimes leading to death in 24-48 hours of initial symptoms Other clinical presentations are also quiete serious like pneumonia, arthritis, endocarditis, myocarditis and Waterhouse-Friederichsen syndrome
Will offer her the available meningococcal vaccine. At Risk Populations: Infants, Children <5 yrs of age, children and adolescents (11-19 yrs) old. High density/crowded populations Dormitory Students Military Recruits Hajj Pilgrims Caregivers and household contacts of infected patients Travelers to endemic areas Industrial or laboratory personnel working with N. Meningitis Immunocompromized/Immunosuppressed patients including those with : Terminal complement deficiencies Anatomic or functional asplenia HIV Cushing K, Cohn A. In: VPD Surveillance Manual, 4 th edition 2008; MMWR 2005; 54(RR-7):1; Bilukha O,et al; Pediatr Infect Dis J;2007;26(5):371;Jodar L.,et al Lancet 2002:359(9316):1499.
2. What are the different serotypes prevalent globally?
3. Epidemiology in India• IAPCOI does not recommend meningococcal vaccination to all children. It is recommended only for High risk individuals. What is the rationale of this?• What is the epidemiology of meningococcal infections in India? A. Endemic B. Sporadic C. Occurs only as outbreaks D. Sporadic with outbreaks
4. What are the various meningococcal vaccines available ?
5. Meningococcal Vaccines Purified capsular polysaccharide vaccines Bivalent vaccine against serogroups A and C Quadrivalent vaccine for serogroups A,C, Y and W135 Protein-polysaccharide conjugate vaccines. Three monovalent meningococcal C conjugate vaccines (Not available in India) Two quadrivalent conjugate vaccine (ACYW135) (Menactra & Menveo--Not available in India) Conjugate vaccines may be a better choice when available in India
6. Why is there no vaccine against serogroup B at present?
7. What are target groups for routine meningococcal vaccination in India ?
8. IAPCOI- High Risk• Age -children > 2 yrs (> 3 months if risk e.g. outbreaks/ contacts , children with terminal complement component deficiencies.• Children with functional/ anatomic asplenia/ hyposplenia (vaccination 2 weeks prior to splenectomy)• Laboratory personnel• Travelers to Saudi Arabia for Haj• Travelers to the African meningitis belt particularly between Dec to June• Adjunct to chemoprophylaxis in close contacts• Students going for study abroad
9. Scenario• Many cases of Meningococcal meningitis reported from Delhi. How many cases make it an outbreak ?• Should meningococcal vaccine be given to all the children? What is the role of meningococcal vaccine during outbreaks? Which vaccine can be used?• What is the role of ‘mass chemoprophylaxis’ during an outbreak situation?
10. Case 1• Nine-mo-old Ishan is hospitalized with meningitis and the doctors say it is meningococcal meningitis.• Should his 4 y sister be administered meningococcal vaccine ?
11. Case 2• Arnav is going for higher studies to Imperial University, London, UK. The university form asks if meningococcal vaccine has been administered.• What vaccine should be given to him and how many doses?• Can he take it just a day prior to his departure ?
12. Case 3• Suhas, 8 years, has recently shifted to US with his parents. He has already received a dose of quadrivalent conjugate meningococcal vaccine one year earlier.• Should he need to take another dose of the meningococcal vaccine?• What are the current recommendations of CDC/ACIP on booster dose of conjugate meningococcal vaccines?
13. ACIP recommended schedule & interval
14. Case 4• A concerned parent from Delhi visits your clinic and enquires about meningococcal disease, its seriousness and prevention in v/o death of his adolescent relative during Delhi epidemic in 2006-07• How will you counsel him?
15. Case 5• The parents of a 15 yrs old girl who came to you for HPV vaccination enquires about meningococcal vaccination since she is planning to go to a hostel in NE region, particularly in v/o a recently occurred mini- outbreak in Mizoram. She is also in constant contact with her 5 yrs old splenectomized brother.• How will you counsel them?