Meningococcal Diseases and Vaccines.pptx

Meningococcal Diseases and Vaccines

1. Meningococcal Disease and Vaccine M Q HASSAN

2. Epidemiology Nasopharyngeal colonisation with  Neisseria meningitidis  is observed in 5–10% of persons and up to 25% in certain populations (highest in adolescents and closed groups). Only a small proportion (<1–5%) progress to IMD. IMD is observed worldwide, with the highest burden of disease in the meningitis belt of sub-Saharan Africa, with approximately 30 000 cases of meningococcal meningitis annually. In 2016, 3 280 confirmed cases of invasive meningococcal disease (IMD), including 304 deaths, were reported in 30 EU/EEA Member States, resulting in an overall notification rate of 0.6 cases per 100 000 population. There is substantial variation in incidence across Member States (Figure 1). Serogroup distribution varies by region of the world. Serogroup B causes the biggest burden of disease in Europe, followed by C, W, and Y. Serogroup B is dominant in all age groups under 65 years of age. In the past few years, there has been an increase of serogroup W, with certain European countries reporting an increase in clonal complex 11. Although rare, there are outbreaks of IMD, such as five confirmed cases caused by serogroup W in Scotland and Sweden in 2015 after attendance at the World Scout Jamboree in Japan. Risk factors for the development of meningococcal disease include age (<5 years of age with a second peak in adolescents and young adults), deficiencies in the terminal complement pathway, functional or anatomic asplenia and underlying chronic disease.

3. Transmission Humans are the only reservoir of  Neisseria meningitidis . Transmission occurs by droplet aerosol or secretions from the nasopharynx of colonised persons. The average incubation period is 3–4 days (usually ranging from 2–10 days). An upper limit to the incubation period is unknown. The infective period effectively stops within 24 hours after the initiation of appropriate antibiotic therapy. The administration of antibiotics to close contacts is recommended as a control measure.

4. Meningococcal disease occurs worldwide, with the highest incidence of disease found in the ‘ meningitis belt ’ of sub-Saharan Africa. In this region, major epidemics occur every 5 to 12 years with attack rates reaching 1,000 cases per 100,000 population. Other regions of the world experience lower overall rates of disease and occasional outbreaks. Annual attack rates in these regions averages around 0.3 to 3 per 100,000 population. In the meningitis belt, serogroup A historically accounted for 90% of meningococcal disease cases and the majority of large-scale epidemics. Starting in 2010, meningitis belt countries began implementing mass vaccination campaigns for a monovalent serogroup A meningococcal conjugate vaccine ( MenAfriVac ®). Held in 22 of the 26 target countries as of December 2018, these campaigns vaccinated 1 through 29 year olds . In addition, 8 countries introduced the vaccine into the routine childhood immunization program. Following vaccine introduction, epidemics due to serogroup A have been  eliminated  pdf icon[8 pages]external icon  in vaccination areas. Recent epidemics have been primarily due to serogroups C and W. Serogroup X outbreaks have also been previously reported in this region. Risk factors for meningococcal disease outbreaks in Africa are not fully understood. However, the following regional characteristics create favorable conditions for meningococcal disease epidemics: Dry and dusty conditions during the dry season between December to June Immunological susceptibility of the population Travel and large population displacements Crowded living conditions. In Europe, the Americas, and Australia, serogroups B, C, and Y together account for a large majority of cases. However, public health officials have observed increasing numbers of serogroup W in some areas. In temperate regions, the number of cases increases in winter and spring. The annual Hajj pilgrimage has also been associated with outbreaks of meningococcal disease due to serogroups A and W.

5. World health statist. quart., 50 (1997)

6. Licensed vaccines against meningococcal disease have been available for more than 40 years. Over time, there have been major improvements in strain coverage and vaccine availability, but to date no universal vaccine against meningococcal disease exists. Vaccines are serogroup specific and confer varying degrees of duration of protection. There are three types of vaccines available: Polysaccharide vaccines are safe and effective in children and adults, but weakly immunogenic in infants. Protection offered is quite short-lived and they do not induce herd protection as they do not prevent carriage. They are still used for outbreak control and  are gradually being replaced by polysaccharide-protein conjugate vaccine Conjugate vaccines are used in prevention  and outbreak response: They confer longer-lasting immunity, prevent carriage and induce herd protection. They are effective in protecting children under two years of age Vaccines are available in different formuations : Monovalent vaccines (serogroup A or C) Tetravalent vaccines (serogroups A, C, Y, W). Combination with other (serogroup C and  Haemophilus influenzae  type b) Protein based vaccine, against  Neisseria meningitidis B .

7. A range of antibiotics can treat the infection, including penicillin, ampicillin and ceftriaxone. Under epidemic conditions in Africa in areas with limited health infrastructure and resources, ceftriaxone is the drug of choice.

8. Epidemics of meningococcal meningitis   Every year, bacterial meningitis epidemics affect more than 400 million people living in the 26 countries of the extended "African meningitis belt" (from Senegal to Ethiopia). In this area over 900 000 cases were reported in the last 20 years (1995–2014). Of these cases, 10% resulted in deaths, with another 10–20% developing neurological sequelae. The most recent large-scale epidemic in the Belt occurred in 2009 and affected mainly Nigeria and Niger, causing over 80 000 reported cases. From 2010 to 2014 cases have been steadily decreasing, with approximately 24 000 cases in 2010 to 11 500 cases in 2014.

9. IMD (invasive meningococcal disease) Meningococcal disease is caused by the bacterium  Neisseria meningitidis . The bacterium is often detected in the nasopharynx without causing disease, a situation described as asymptomatic carriage. The bacteria occasionally invade the body and cause  meningococcal  infection, which is an acute severe bacterial infection. Invasive meningococcal disease (IMD) is a major cause of meningitis and septicaemia . The disease often has a rapid progression, with an 8–15% case-fatality ratio. The highest incidence occurs in young children, with a second disease peak among adolescents and young adults. IMD is notifiable and under surveillance in EU/EEA countries. The overall notification rate was 0.6 per 100 000 persons in 2016, according to data reported to ECDC through The European Surveillance System ( TESSy ). Serogroups B and C are the most common causes of IMD in Europe, but there is an increase of serogroup W in the past few years. Outbreaks of meningococcal disease are rare, but can occur in settings where people group together, such as college campuses and military recruits. Vaccines are available for primary prevention of disease caused by serogroups A, B, C, W, and Y. Antibiotics are available for elimination of carriage and treatment of disease.

10. Key facts Meningococcal meningitis is a bacterial form of meningitis, a serious infection of the thin lining that surrounds the brain and spinal cord. Meningococcal meningitis is associated with high fatality (50% when untreated) and high frequency (10-20%) of severe long-term sequelae. Early antibiotic treatment is the most important measure to save lives and reduce complications. Meningococcal meningitis is observed worldwide; the highest burden of the disease is in the meningitis belt of sub-Saharan Africa, stretching from Senegal in the west to Ethiopia in the east. Serogroup specific vaccines are used for prevention and in response to outbreaks. Since 2010 and the roll-out of a meningococcal A conjugate vaccine through mass preventive immunization campaigns in the meningitis belt, the proportion of the A serogroup has declined dramatically.

11. Meningococcal Rashes

12. Meninges, Skin involvement

13. Clinical criteria Any person with at least one of the following symptoms: meningeal signs haemorrhagic rash septic shock septic arthritis Laboratory criteria At least one of the following: isolation of  Neisseria meningitidis  from a normally sterile site or purpuric skin lesions detection of  Neisseria meningitidis  nucleic acid from a normally sterile site or purpuric skin lesions detection of  Neisseria meningitidis  antigen in cerebrospinal fluid (CSF) detection of gram-negative stained diplococcus in CSF

14. Clinical features and sequelae Meningitis (30–60%) and sepsis (20–30%) are the major clinical features of IMD. Less common are other focal diseases such as pneumonia and arthritis. Meningitis frequently presents with the triad of fever, headache and neck stiffness, and is often accompanied by other symptoms, such as altered mental status, nausea, vomiting and photophobia. Meningococcal sepsis (meningococcemia) is characterised by fever and a petechial or purpuric rash, often accompanied by septic shock, disseminated intravascular coagulation and multiple organ failure. Meningococcemia has a case-fatality ratio of up to 40%. Sequelae such as neurological and hearing impairment or amputation occur in up to 20% of survivors.

15. Diagnostics The diagnosis of IMD is based on bacteriologic isolation, antigen or DNA detection of  Neisseria meningitidis  in a usually sterile body fluid such as blood, CSF or synovial or pleural fluid. The sensitivity of culture is reduced after the initiation of antimicrobial therapy and polymerase chain reaction-based assays are increasingly used for the diagnosis of meningococcal disease. Microbiological confirmation is necessary to fulfil the case definition of a confirmed case according to the EU case definition.

16. Case management and treatment Prompt recognition of disease and administration of antibiotics, usually beta-lactam, are vital to improve the outcome in IMD. Options for contact management of sporadic cases of IMD is illustrated in an ECDC guidance [2]. However, this may differ according to setting and context and national/regional guidances available in the EU/EEA should be consulted. Household contacts should be offered chemoprophylaxis with an antibiotic regimen that eradicates carriage. Attending the same school/college as an IMD case should not in itself be an indication for chemoprophylaxis, nor is sharing the same transport vehicle or drinks, cigarettes or similar contact with a case of IMD, in itself an indication for chemoprophylaxis. Rifampicin, ciprofloxacin, ceftriaxone, azithromycin and cefixime can be used for prophylaxis in adults and children. No specific regimen has been proven to be superior, but ciprofloxacin, azithromycin and ceftriaxone can be given as a single dose. Furthermore, given the relatively low cost of intervention, antibiotics that eradicate carriage should be offered to IMD cases if not already used in treatment. If a case of meningococcal disease is caused by a strain that is preventable by an available licensed vaccine, vaccination in addition to chemoprophylaxis should be offered to household contacts unless they are considered to be already immune.

17. Chemoprophylaxis Antibiotic prophylaxis for close contacts, when given promptly, decreases the risk of transmission. Outside the African meningitis belt, chemoprophylaxis is recommended for close contacts within the household. In the meningitis belt, chemoprophylaxis for close contacts is recommended in non-epidemic situations. Ciprofloxaci n antibiotic is the antibiotic of choice, and ceftriaxone an alternative.

18. Global public health response – virtual elimination of meningococcal A meningitis epidemics in the African meningits belt In the African meningitis belt, Neisseria meningitidis serogroup A accounted for 80–85% of meningitis epidemics before the introduction of a meningococcal A conjugate vaccine ( MenACV ) through mass preventive campaigns (since 2010) and into routine immunization programmes (since 2016). As of April 2021, 24 of the 26 countries in the meningitis belt have conducted mass preventive campaigns targeting 1-29 years old population (nationwide or in high-risk areas), and half of them have introduced MenACV into their national routine immunization schedules. Among vaccinated populations, incidence of NmA meningitis has declined by more than 99% - no NmA case has been confirmed since 2018. Continuing introduction into routine immunization programmes and maintaining high coverage is critical to avoid the catastrophic resurgence of NmA epidemics. Cases of meningitis and outbreaks due to other serogroups ( NmC , NmW and NmX ) continue to strike. The roll out of multivalent meningococcal conjugate vaccines to eliminate bacterial meningitis epidemics is an objective of the Defeating Meningitis by 2030 road map.

19. Public health control measures Advances in the control of meningococcal disease have taken place over the past decades through prophylactic vaccination. Vaccination against IMD is part of  general immunisation programs  in certain EU/EEA Member States, while other countries only recommend the vaccination of specific risk groups. All licenced meningococcal vaccines are inactivated. There are polysaccharide and polysaccharide-conjugated vaccines based on the capsules of serotypes A, C, Y and W. An advantage of conjugate vaccines is their ability to generate an immunological memory. Due to similarities with the neural cell adhesive molecule, a human glycoprotein, the serogroup B capsule is poorly immunogenic as an antigen. Vaccines against serogroup B are based on surface proteins of  Neisseria meningitidis  group B. The following meningococcal vaccines are approved for use in the EU based on a centralised licensing procedure: Menveo ® (meningococcal groups A, C, W-135 and Y conjugate vaccine) is indicated for the immunisation of children from two years of age, adolescents and adults at risk of exposure to  Neisseria meningitidis  groups A, C, W-135 and Y to prevent invasive disease. Nimenrix ® (meningococcal groups A, C, W-135 and Y conjugate vaccine) is indicated for the immunisation of individuals from the age of six weeks against IMD caused by  Neisseria meningitidis  groups A, C, W-135 and Y. Bexsero ® (meningococcal group B surface protein vaccine) is indicated to protect individuals from the age of two months against IMD caused by  Neisseria meningitidis serogroup B. Trumemba ® (meningococcal group B surface protein vaccine) is indicated for active immunisation of individuals 10 years and older to prevent IMD caused by  Neisseria meningitidis  serogroup B. Other meningococcal vaccines, such as meningococcal serogroup C conjugate vaccines, meningococcal A polysaccharide vaccines, meningococcal groups A, C, W-135 and Y polysaccharide vaccine and one combination vaccine with a  Haemophilus influenzae B  (Hib) component have been licensed by national health authorities in their respective Member States.

20. Travel requirements Travellers who wish to enter or leave certain countries or territories must be vaccinated against meningococcal meningitis, preferably 10–14 days before crossing the border, and be able to present a vaccination record/certificate at the border checks. Countries with required meningococcal vaccination for travellers include  The Gambia ,  Indonesia ,  Lebanon ,  Libya , the  Philippines , and most importantly and extensively  Saudi Arabia  for Muslims visiting or working in  Mecca  during the  Hajj  or  Umrah  pilgrimages. For some countries in  African meningitis belt , vaccinations prior to entry are not required, but highly recommended.

21. Vaccine highlights meningococcal groups A, C, W-135 and Y conjugate vaccine from the age of 6 weeks against invasive meningococcal disease caused by four groups of the bacterium  Neisseria meningitidis  (group A, C, W-135, and Y). Meningitis and SEPTICAEMIA IM vaccine

22. Vaccine Recommendations In infants from 6 wks to less than 6 months of age, two doses of Nimenrix are recommended (the first dose is given from 6 weeks of age, the second dose 2 months afterwards ). Children from 6 months of age, adolescents and adults should be given one dose of Nimenrix , but an additional dose may be considered for some children at high risk of invasive meningococcal disease (at least 2 months after the last dose of Nimenrix ). Children who received the initial dose (or doses) of Nimenrix between 6 weeks and one year of age should receive a booster dose at 1 year of age , at least 2 months after the last dose of Nimenrix . Nimenrix may also be used as a booster vaccine in people from 1 year of age who have already been vaccinated with another meningococcal vaccine, to reinforce the level of protection.

23. How do they work Vaccines work by preparing the immune system (the body’s natural defences ) to defend itself against a specific disease. When a person is given the vaccine, the immune system recognises the parts of the bacterium in the vaccine as ‘foreign’ and makes antibodies against them. When the person comes into contact with the bacterium, these antibodies, together with other components of the immune system, will be able to kill the bacteria and help protect against the disease.

24. How Safe? How long gives protection Any boost needed? PRICE Storage - Practicality in administering

25. Meningococcal vaccines are generally safe. [1]  Some people develop pain and redness at the injection site. [1]  Use in pregnancy appears to be safe. [5]   Severe allergic reactions  occur in less than one in a million doses. [1] The first meningococcal vaccine became available in the 1970s. [7]  It is on the  World Health Organization's List of Essential Medicines . [8]

26. The  World Health Organization  recommends that countries with a moderate or high rate of disease or with frequent outbreaks should  routinely vaccinate . [1] [5]  In countries with a low risk of disease, they recommend that high risk groups should be immunized. [1]  In the  African meningitis belt  efforts to immunize all people between the ages of one and thirty with the meningococcal A  conjugate vaccine  are ongoing. [5]  In Canada and the United States the vaccines effective against four types of meningococcus (A, C, W, and Y) are recommended routinely for teenagers and others who are at high risk. [1]   Saudi Arabia  requires vaccination with the quadrivalent vaccine for international travelers to  Mecca  for  Hajj . [1] [6]

27. Types[ edit ] Neisseria meningitidis  has 13 clinically significant  serogroups , classified according to the antigenic structure of their polysaccharide capsule. Six serogroups, A, B, C, Y, W-135, and X, are responsible for virtually all cases of the disease in humans. Quadrivalent (Serogroups A, C, W-135, and Y) [ edit ] There are three vaccines available in the United States to prevent meningococcal disease, all quadrivalent in nature, targeting serogroups A, C, W-135, and Y: three  conjugate vaccines  (MCV-4), Menactra , Menveo and MenQuadfi . The pure polysaccharide vaccine Menomune , MPSV4, was discontinued in the United States in 2017. Menveo and MenQuadfi are approved for medical use in the European Union. [9] [10]

28. Menveo The first meningococcal conjugate vaccine (MCV-4), Menactra , was licensed in the U.S. in 2005 by  Sanofi Pasteur ; Menveo was licensed in 2010 by  Novartis . Both MCV-4 vaccines have been approved by the  Food and Drug Administration  (FDA) for people 2 through 55 years of age. Menactra received FDA approval for use in children as young as 9 months in April 2011 [11]  while Menveo received FDA approval for use in children as young as two months in August 2013. [12]  The  Centers for Disease Control and Prevention  (CDC) has not made recommendations for or against its use in children less than two years. [13] Menomune Meningococcal polysaccharide vaccine (MPSV-4), Menomune , has been available since the 1970s. It may be used if MCV-4 is not available, and is the only meningococcal vaccine licensed for people older than 55. Information about who should receive the meningococcal vaccine is available from the CDC. [13] Nimenrix Nimenrix (Pfizer). Meningoccal group A, C, W-135 and Y conjugate vaccine Nimenrix (developed by GlaxoSmithKline and later acquired by  Pfizer ), is a quadrivalent conjugate vaccine against serogroups A, C, W-135, and Y. [14]  In April 2012 Nimenrix was approved as the first quadrivalent vaccine against invasive meningococcal disease to be administered as a single dose in those over the age of one year, by the European Medicines Agency. [15]  In 2016, they approved the vaccine in infants six weeks of age and older, and it has been approved in other countries including Canada and Australia, among others. [16] [17]  It is not licensed in the United States. [18] Mencevax Mencevax ( GlaxoSmithKline ) and  NmVac4-A/C/Y/W-135  ( JN-International Medical Corporation ) are used worldwide, but have not been licensed in the United States.

29. NIMENRIX Nimenrix contains small amounts of capsular polysaccharides (sugars from the outer coat) extracted from the four groups of the  N. meningitidis  bacterium: A, C, W135 and Y. These have been purified and then ‘ conjugated’ (attached) to a protein carrier called tetanus toxoid (a weakened toxin of tetanus which does not cause disease, also used in tetanus vaccine), because this improves the immune response to the vaccine. Capsular Poly saccharide + TT protein - conjugation

30. Limitations The duration of immunity mediated by Menomune (MPSV-4) is three years or less in children aged under five because it does not generate  memory T cells . Attempting to overcome this problem by repeated immunization results in a diminished, not increased,  antibody  response, so boosters are not recommended with this vaccine. As with all polysaccharide vaccines, Menomune does not produce  mucosal immunity , so people can still become colonised with virulent strains of meningococcus, and no  herd immunity  can develop. [23] [24]  For this reason, Menomune is suitable for travelers requiring short-term protection, but not for national public health prevention programs. Menveo and Menactra contain the same antigens as Menomune , but the antigens are conjugated to a  diphtheria toxoid  polysaccharide–protein complex, resulting in anticipated enhanced duration of protection, increased immunity with booster vaccinations, and effective herd immunity.

31. Endurance A study published in March 2006, comparing the two kinds of vaccines found that 76% of subjects still had passive protection three years after receiving MCV-4 (63% protective compared with controls), but only 49% had passive protection after receiving MPSV-4 (31% protective compared with controls). As of 2010, there remains limited evidence that any of the current conjugate vaccines offer continued protection beyond three years; studies are ongoing to determine the actual duration of immunity, and the subsequent requirement of booster vaccinations. The CDC offers recommendations regarding who they feel should get booster vaccinations.

32. Bivalent (Serogroups C and Y) On 14 June 2012, the FDA approved a combination vaccine against two types of meningococcal disease and  Hib disease  for infants and children 6 weeks to 18 months old. The vaccine, Menhibrix , prevents disease caused by  Neisseria meningitidis   serogroups  C and Y and  Haemophilus influenzae  type b. This was the first meningococcal vaccine that could be given to infants as young as six weeks old. Serogroup A A vaccine called  MenAfriVac  has been developed through a program called the  Meningitis Vaccine Project  and has the potential to prevent outbreaks of group A meningitis, which is common in sub-Saharan Africa

33. Serogroup B [ edit ] Vaccines against serotype B meningococcal disease have proved difficult to produce, and require a different approach from vaccines against other serotypes. Whereas effective  polysaccharide  vaccines have been produced against types A, C, W-135, and Y, the capsular polysaccharide on the type B bacterium is too similar to  human neural adhesion molecules  to be a useful target. [32] A number of "serogroup B" vaccines have been produced. Strictly speaking, these are not "serogroup B" vaccines, as they do not aim to produce antibodies to the group B antigen: it would be more accurate to describe them as serogroup independent vaccines, as they employ different antigenic components of the organism; indeed, some of the antigens are common to different  Neisseria  species. [ medical citation needed ] A vaccine for serogroup B was developed in  Cuba  in response to a large outbreak of meningitis B during the 1980s. This vaccine was based on artificially produced  outer membrane vesicles  of the bacterium. The VA-MENGOC-BC vaccine proved safe and effective in randomized double-blind studies, [33] [34] [35]  but it was granted a licence only for research purposes in the United States [36]  as political differences limited cooperation between the two countries. [37] Due to a similarly high prevalence of B-serotype meningitis in  Norway  between 1975 and 1985, Norwegian health authorities developed a vaccine specifically designed for Norwegian children and young adolescents. [ citation needed ]  Clinical trials were discontinued after the vaccine was shown to cover only slightly more than 50% of all cases. Furthermore, lawsuits for damages were filed against the State of Norway by persons affected by serious adverse reactions. Information that the health authorities obtained during the vaccine development were subsequently passed on to  Chiron  (now GlaxoSmithKline), who developed a similar vaccine,  MeNZB , for New Zealand. [ citation needed ] A MenB vaccine was approved for use in Europe in January 2013. Following a positive recommendation from the  European Union 's  Committee for Medicinal Products for Human Use , Bexsero , produced by  Novartis , received a licence from the  European Commission . [38]  However, deployment in individual EU member countries still depends on decisions by national governments. In July 2013, the  United Kingdom 's  Joint Committee on Vaccination and Immunisation  (JCVI) issued an interim position statement recommending against adoption of Bexsero as part of a routine meningococcal B immunisation program, on the grounds of cost-effectiveness. [39]  This decision was reverted in favor of Bexsero vaccination in March 2014. [40]  In March 2015 the UK government announced that they had reached agreement with  GlaxoSmithKline  who had taken over  Novartis ' vaccines business, and that Bexsero would be introduced into the UK routine immunization schedule later in 2015. [41] In November 2013, in response to an outbreak of B-serotype meningitis on the campus of  Princeton University , the acting head of the  Centers for Disease Control and Prevention  (CDC) meningitis and vaccine preventable diseases branch told  NBC News  that they had authorized emergency importation of Bexsero to stop the outbreak. [42]   Bexsero was subsequently approved by the FDA in February 2015. [43]  In October 2014, Trumenba , a serogroup B vaccine produced by  Pfizer , was approved by the FDA. [2] Serogroup X [ edit ] The occurrence of serogroup X has been reported in North America, Europe, Australia, and West Africa. [44]  There is no vaccine to protect against serogroup X  N. meningitidis  disease. [1]

34. Side effects Common side effects include pain and redness around the site of injection (up to 50% of recipients). A small percentage of people develop a mild fever. A small proportion of people develop a severe allergic reaction. In 2016 Health Canada warned of an increased risk of anemia or  hemolysis  in people treated with  eculizumab  (Soliris). The highest risk was when individuals "received a dose of Soliris within 2 weeks after being vaccinated with Bexsero". Despite initial concerns about  Guillain-Barré syndrome , subsequent studies in 2012 have shown no increased risk of GBS after meningococcal conjugate vaccination.

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