The remedy is worse than the disease.
Francis Bacon
21-02-2018 09:59
  1. Meningococcus is the third type of bacteria causing meningitis and bacteremia. The incidence of meningococcal infection is significantly lower than the incidence of pneumococcal and Haemophilus influenzae infections, but since meningococcal vaccine is the newest licensed vaccine, meningococcus has recently become the biggest horror story.

  2. CDC Pinkbook Meningococcal

    There are 13 serogroups of meningococcus, but these five are mainly responsible for the invasive infections: A, B, C, W, Y. 60% of invasive infections in children are caused by the serogroup B.
    Mortality rate of invasive infections is 10-15%, and mortality rate of meningococcemia (meningococcal sepsis) is up to 40%.
    Risk factors include active and passive smoking, alcohol, crowding and asplenia (absence of spleen).
    98% of cases are sporadic, and only 2% happen due to outbreaks.
    The first polysaccharide vaccine was introduced in 1974. Same as other polysaccharide vaccines, it is ineffective for infants.
    The first meningococcal conjugate vaccine (Menactra) was lincensed in 2005 for teenagers over 11 years of age. The second vaccine (Menveo) was licensed in 2010. Both vaccines protect from ACWY serogroups. The vaccines were expected to be effective for 10 years, but it turned out, that the number of antibodies decreases after 3-5 years already, and those vaccinated at 11 years old, will no longer be protected at the age of 16-21 years, when the risk of meningococcal infection is higher. Thus, in 2010 revaccination was added at the age of 16 years old.
    30 cases of infection in those vaccinated, were registered with CDC in 2006-10. The mortality rate for them was the same as for those unvaccinated.
    In 2014-15, two vaccines against serogroups B were licensed: Bexsero (GSK) and Trumenba (Pfizer), but they have not been added to the vaccination schedule yet.

  3. Advances in the development of vaccines against Neisseria meningitidis. 2010, Tan, N Engl J Med

    The incidence of meningococcal infection is 1 in every 300,000 in the USA, and an average of 1 in every 100,000 in Europe.
    It was believed previously that the highest incidence is among children of the 6-24 months age group, but recent data suggests that it is infants under the age of 6 months, who did not get antibodies from the mother, that suffer most.
    Polysaccharide vaccines for ACWY serogroups are ineffective for infants.
    Most cases of the infection happen with serogroup B, but since the capsule of this serogroup contains a molecule, which is very similar to glycoproteins in the brain, polysaccharide vaccines for this group produce antibodies poorly, and can cause an autoimmune response due to the molecular mimicry mechanism. Therefore, vaccines based on outer membrane proteins were developed.
    However, since meningococcal outer membrane proteins can change antigens, it can cause vaccine ineffectiveness.
    Since meningococcal infection is a rare disease, all meningococcal vaccines were licensed based on immunogenicity only (i.e. the level of antibodies), and not on the clinical effectiveness.

  4. Changes in Neisseria meningitidis disease epidemiology in the United States, 1998-2007: implications for the prevention of meningococcal disease. 2010, Cohn, Clin Infect Dis

    Between 1998 and 2007, the incidence of meningococcal infection decreased by 64%. On average, the incidence was 1 in 20 thousand during these years, and by 2007, it decreased to 1 in 300 thousand.
    The highest incidence was among infants under 1 year of age (5 in 100 thousand). 50% of the cases in them were caused by serogroup B, and two thirds of the cases that happened in infants under 6 months old.
    Black people get infected 44% more often than white people.
    The mortality rate of meningococcal infection was 11%, and increased with age. The mortality rate among the elderly was 24%, and 3-6% among infants.
    The most cases were observed in January and February, and the least in August.
    The authors conclude that before the introduction of vaccination, the incidence of meningococcal infection in the USA was at a historical minimum, and that after the introduction of vaccination, there was no significant decrease in the incidence among teenagers, who were vaccinated, because only 32% have been vaccinated.
    (The tune that runs through almost all studies: If there was no significant decrease in incidence after the introduction of a vaccine - that is because the coverage was insufficient, but if there was a decrease – that is, obviously, due to vaccination, even if only 2% had been vaccinated).

  5. Changes in bacterial meningitis. 1990, Carter, Arch Dis Child

    The mortality rate of meningococcal infection in Scotland decreased from 10.3% in 1946-61 to 1.2% in 1971-86. The incidence decreased from 7.9 to 5.3 per 100,000 children.
    The incidence of Haemophilus influenzae infection during this time increased by 4, while the mortality rate decreased from 19.2% to 3%.

  6. A retrospective epidemiological study of bacterial meningitis in an urban area in Belgium. 1997, van Hoeck, Eur J Pediatr

    The incidence of bacterial meningitis in Belgium increased 10-fold between 1988 and 1993, mainly due to meningococcus. Immigrants and non-white people got infected more often.

  7. Human immunity to the meningococcus, II. Development of natural immunity. 1969, Goldschneider, J Exp Med

    As a result of asymptomatic colonization of meningococcus, meningococcus antibodies are produced within several weeks.
    Infant under 6 months of age are protect by their mothers’ antibodies. Concentration of antibodies in the blood of infants is higher than in the blood of mothers.
    Natural immunity is usually produced in childhood.

  8. Neisseria meningitidis: an overview of the carriage state. 2004, Yazdankhah, J Med Microbiol

    10% of the population are carriers of meningococcal bacteria. Less than 3% are infected among children, but 24-37% are infected among the 15-24 years age group. High level of colonization is also observed in the army. For example, more than 70% were meningococcus carriers among the Norwegian soldiers.
    A recent study showed that the number of meningococcus carriers, determined by conventional methods (bacterial cultures), might be underestimated. Using a different method (immunohistochemistry) showed that 45% were carriers of meningococcus, while conventional methods found meningococcus only in 10% of them.
    Colonization of meningococcus leads to production of antibodies within several weeks of infection, and can protect from the disease.
    About 50% of the strains, found in carriers, turned out to be noncapsular. It was believed previously, that noncapsular strains were not pathogenic, but it turned out that meningococci are able to turn on and off the production of capsules frequently. There is evidence that the loss of a capsule enhances the ability of meningococci to colonize the nasopharynx, and avoid the body’s defense system. More: [1]

  9. Meningococcal disease: history, epidemiology, pathogenesis, clinical manifestations, diagnosis, antimicrobial susceptibility and prevention. 2006, Manchanda, Indian J Med Microbiol

    Chronic benign meningococcemia may develop in less than 1%. How these patients tolerate potentially lethal bacteria in the bloodstream for several weeks is unknown.

  10. The risk of meningococcal disease in travelers and current recommendations for prevention. 2010, Steffen, J Travel Med

    Meningococcal disease outbreaks often occurred among pilgrims in Mecca, so Saudi Arabia introduced mandatory vaccination for those applying for the Hajj visa. No more outbreaks have been observed after that.
    Meningococcal disease is most common in the “African meningitis belt,” which includes sub-Saharan countries. Most cases are reported during the dry season. However, there is not a single known case of tourists getting infected.
    CDC investigates potential infection with meningococcus on an airplane every 6 weeks. However, only two of such cases are known.

  11. Risk Factors

  12. Tobacco smoke as a risk factor for meningococcal disease. 1997, Fischer, Pediatr Infect Dis J

    The risk of meningococcal infection in a child under 18 years of age, increases by 3.8 times if their mother smokes.
    Smoking increases the risk of meningococcal infection in adults by 2.4 times, passive smoking by 2.5 times, and chronic disease by 10.8 times.

  13. Second hand smoke exposure and the risk of invasive meningococcal disease in children: systematic review and meta-analysis. 2012, Murray, BMC Public Health

    Passive smoking increases the risk of meningococcal infection by 2.2 times. When both parents smoke, the risk increases by 8 times. More: [1] [2] [3]
    In Ghana, where meningococcal meningitis is much more common than in developed countries, cooking in wood-burning ovens is associated with a 9-fold higher risk of infection.

  14. Passive smoking, invasive meningococcal disease and preventive measures: a commentary. 2012, Rashid, BMC Med

    When parents only smoke outside of the house, it does not decrease the level of nicotine in the children’s hair, which might indicate that the smokers continue to exhale nicotine after smoking. This hints at that the risk of meningococcal infection will not decrease if smoking is prohibited only in certain places, like homes, cars and hospitals, but a full ban is needed. It is known, however, that a relatively small number of people quit smoking, so vaccinating children will probably be more effective. Moreover, there’s hope that children will be able to protect their smoking parents from meningococcus through collective immunity.

  15. Increased Risk for Meningococcal Disease Among Men Who Have Sex With Men in the United States, 2012-2015. 2017, Folaranmi, Clin Infect Dis

    The risk of meningococcal infection in homosexuals in 4 times higher, than in heterosexual people. HIV positive homosexuals suffer from meningococcal disease 10 times more often, than HIV negative ones. 45% of meningococcus patients reported multiple partners and participation in anonymous sex.
    Among homosexuals, 32% smoke (as compared to 18% among adults in the USA), and 48% are drug users (as compared to an average of 10%).
    In New York and Southern California, the risk of meningococcal infection among homosexuals was 50 times higher, than in general; in Germany, it was 13 times higher; and in Paris – 10 times higher.
    24% of homosexuals are carriers of meningococcus, as compared to 6% of heterosexual women. Among homosexuals, who have had oral-anal contact recently, 43% were carriers.
    Meningococcus was also found in the anal canal in 4.5% of homosexuals.
    A new strain of meningococcus that can be transmitted sexually was discovered in 2016.
    CDC reports that in 2016, 57% of men over 16 years of age infected with meningococcus, reported homosexual relations. More: [1] [2] [3].

  16. Invasive meningococcal disease among men who have sex with men. 2013, ECDC,

    HIV infection increases the risk of meningococcal infection by 11 times, and AIDS increases the risk by 12 times.
    A meningococcus outbreak among homosexual began in New York in 2010. This is connected to the mobile dating apps and attending gay-bars.

  17. Risk and protective factors for meningococcal disease in adolescents: matched cohort study. 2006, Tully, BMJ

    Intimate kisses with multiple partners are associated with a 3.7 fold increase in the risk of meningococcal infection among teenagers. Preterm delivery is also associated with a 3.7 fold increase in the risk of infection. Previous disease increased the risk by 2.9 times.
    Religious ceremonies are associated with an 11 times decrease, and vaccination is associated with an 8 times decrease, in the risk of infection.
    Marijuana is associated with a 4.2 times increase in the risk of meningococcal infection, and attending nightclubs by 3.3 times. Attending picnics and dances decreased the risk by 3-4 times.

  18. Prolonged university outbreak of meningococcal disease associated with a serogroup B strain, rarely seen in the United States. 2013, Mandal, Clin Infect Dis

    Meningococcus outbreak in a university in Ohio (13 cases). Attending bars was associated with an 8 times increase in the risk of infection, and kissing more than one partner with a 13.6 times increase.
    Crowding (more than 2.5 people per bedroom), low level of education in mothers, low income level, alcohol abuse and chronic illness have been risk factors of meningococcal infection in Chile.
    Low level of education in parents is associated with a two fold increase in the risk of meningococcus colonization in Brazil, which probably reflects the socioeconomic conditions.
    Crowding and previous acute respiratory infections are associated with a 3 fold increase in infection in children, and father’s smoking is associated with a 4.5 fold increase, in Greece. More: [1] [2]

  19. Effectiveness

  20. Updated Recommendations for the Use of Meningococcal Conjugate Vaccines - Advisory Committee on Immunization Practices (ACIP), 2010. 2011, CDC, JAMA

    Clinical effectiveness of Menactra a year after vaccination is 91%, and in 2-5 years, it decreases to 58% (CI: -72 - 89).

  21. Effectiveness of meningococcal serogroup C conjugate vaccine 4 years after introduction. 2004, Trotter, Lancet

    A meningococcal conjugate vaccine (serogroup C) was added to the national immunization schedule for infants at the age of 2, 3 and 4 months, in England in 1999. Vaccine effectiveness was 93% during the first year after vaccination, but became negative (-81%) after a year. Immunity after vaccination at an older age lasts longer.

  22. Effect of the outer membrane vesicle vaccine against the group B meningococcal disease in Norway. 1991, Bjune, Lancet

    The highest incidence of meningococcal infection in Europe is observed in Norway, and 80% of them are serogroup B cases. (There was an epidemic there in the 1970-80s, and the incidence was 1 in 14-21,000).
    A double-blind, randomized study (170,000 people) was conducted on an outer membrane vaccine (OMV). Aluminum hydroxide was used as placebo. Vaccine effectiveness was only 57%, so it was decided not to include it in the immunization schedule.

  23. Efficacy, safety, and immunogenicity of a meningococcal group B (15:P1.3) outer membrane protein vaccine in Iquique, Chile. Chilean National Committee for Meningococcal Disease. 1995, Boslego, Vaccine

    Clinical trial of serogroup B vaccine in Chile (40,000 people). Other meningococcal serogroups vaccine was used as placebo. Vaccine effectiveness was 51% during 2.5 years, and among children under 5 years old, effectiveness was negative (-23%).

  24. Antibody persistence following MeNZB vaccination of adults and children and response to a fourth dose in toddlers. 2011, Jackson, Arch Dis Child

    Meningococcal serogroup B epidemic began in New Zealand in 1991. By 2001, it reached its peak and began to decline.
    By 2004, a special vaccine for New Zealand strain was developed. Since conducting randomized trials during epidemic was considered unethical, vaccination campaign for all children from the age of 6 weeks to 19 years was launched in 2004. By 2006, 80% of children have been vaccinated, and the campaign was discontinued.
    7 months after the third dose of the vaccine, the number of antibodies in infants returned to almost the original level. More: [1]
    Detailed journalistic investigation of this campaign: [1] [2]

  25. High Risk for Invasive Meningococcal Disease Among Patients Receiving Eculizumab (Soliris) Despite Receipt of Meningococcal Vaccine. 2017, McNamara, Am J Transplant

    Eculizumab is a medicine for very rare diseases, which suppresses the complement system (one of the components of innate immune system). This medicine is associated with a 1,000-2,000 increase in the risk of meningococcal infection.
    16 people using this medicine got meningococcemia, 14 of them have been vaccinated.

  26. Factor H is one of the proteins regulating the complement system. Being bound to a cell, factor H suppresses the complement system’s response to this cell, and in its unbound form, it enhances this same reaction to microorganisms. If bacteria have protein capable of binding to factor H, then they can avoid being attacked by complement system. This mechanism is part of the virulence of some bacteria, including meningococcus.
    Since previous types of meningococcal serogroup B vaccines (polysaccharide, conjugate and outer membrane vaccines) turned out to be ineffective, the protein binding factor H has been added to new vaccines (Bexsero and Trumenba), in the hopes that it will lead to higher effectiveness.
    Antibodies, produced after Bexsero vaccine in animals, were cross-reactive with human factor H. It is currently unknown, whether antibodies for factor H are produces in humans, and whether this will increase the risk of autoimmune response.
    (Antibodies, cross-reactive with factor H, can also cause suppression of the complement system, which is key in suppressing the meningococcal infection by the body).

  27. Capsule switching of Neisseria meningitidis. 1997, Swartley, Proc Natl Acad Sci U S A

    Meningococcal bacteria, same as pneumococcus, are able to change their serogroups.

  28. Invasive meningococcal disease in Quebec, Canada, due to an emerging clone of ST-269 serogroup B meningococci with serotype antigen 17 and serosubtype antigen P1.19 (B: 17: P1.19). 2006, Law, J Clin Microbiol

    Serogroup B meningococcal disease outbreak in Québec in 2004. The authors believe that it probably happened due to serogroup replacement due to vaccination with the polysaccharide vaccine against serogroup C.

  29. Colonization

  30. Meningococcal Carriage Evaluation in Response to a Serogroup B Meningococcal Disease Outbreak and Mass Vaccination Campaign at a College-Rhode Island, 2015-2016. 2017, Soeters, Clin Infect Dis

    Serogroup B meningococcal infection outbreak occurred in a college in Rhode Island in early 2015 (two cases). Both recovered. As a result of the outbreak, 5 three-dose vaccination campaigns were conducted for students and teachers on campus, as well as for their intimate partners. A total of about 4,000 people had been vaccinated with the newly licensed Trumenba vaccine. Since it was unknown, how this vaccine affected colonization, the authors used this vaccination campaign determine it.
    20%-24% were carriers of meningococcus, and 4% were carriers of serogroup B. The risk of colonization was 30% higher in smokers, and among those who attend bars and clubs at least once a week, the risk of colonization was 80% higher. The authors concluded that vaccination does not affect colonization of meningococcus and herd immunity, and therefore, high vaccination coverage is necessary.

  31. Meningococcal carriage among a university student population - United States, 2015. 2018, Breakwell, Vaccine

    A study of meningococcal colonization in another university in Rhode Island.
    Vaccination did not affect colonization. Smoking was associated with a 1.5 times increase in the risk of colonization, and attending bars at least once a week – with a 2 times increase.

  32. Meningococcal Carriage Following The Vaccination Campaign With MenB-4C and MenB-FHbp in Response to a University Serogroup B Meningococcal Disease Outbreak-Oregon, 2015-2016. 2017, McNamara, J Infect Dis

    A vaccination campaign was conducted, as a result of an outbreak in a university in Oregon. 11%-17% were carriers of meningococcus, of them 1.2%-2.4% were carriers of serogroup B. Vaccination with 1-2 doses of Bexsero and 1-3 doses of Trumenba, did not affect the meningococcal colonization in general, and colonization of the serogroup B in particular.

  33. Rise in Group W Meningococcal Carriage in University Students, United Kingdom. 2017, Oldfield, Emerg Infect Dis

    Vaccination of teenagers with a conjugate vaccine (against serogroups ACWY) has recently started in England. The authors tested for meningococcal colonization before and after vaccination at a university, and it turned out that despite the 71% vaccination coverage, the colonization increased from 14% to 46%, and serogroup W colonization increased 11-fold, from 0.7% to 8%.

  34. Miscellaneous

  35. Dr. Rodewald, head of the vaccination department at CDC, stated in 2004 that CDC was not doing well with vaccination of teenagers, and therefore, intimidating parents about the consequences of not vaccinating their children will become part of the advertising campaign, and that meningococcal vaccine is perfect for this purpose. Since after the meningococcal vaccine, vaccines against tetanus, diphtheria and whooping cough, as well as the HPV and herpes vaccines, will need to be added to the immunization schedule.
    The article also says that vaccination is usually much cheaper than the cost of treatment, but not in the cases of meningococcus. Vaccination will cost $3.5 billion per year, and each saved life will cost more than a million dollars. More: [1 (p.13)]

  36. Depressive symptoms and immune response to meningococcal conjugate vaccine in early adolescence. 2014, O'Connor, Dev Psychopathol

    Depressed children developed more antibodies after meningococcal vaccine, than children not suffering from depression.

  37. Safety

  38. Guillain-Barré syndrome among the recipients of Menactra meningococcal conjugate vaccine - United States, June-July 2005. 2005, CDC, MMWR Morb Mortal Wkly Rep

    Menactra was licensed in January of 2005, and was recommended for 11-12 year olds, as well as for university freshmen. 5 cases of the Guillain-Barré syndrome were registered with VAERS among vaccinated freshmen between June 10th and July 25th of 2005. In one case, the vaccinated girl already had Guillain-Barré syndrome twice before, at the ages of 2 and 5 years; both times within 2 weeks of vaccination.
    CDC concludes that it might be a coincidence, and recommends continuing vaccination. The manufacturer added to the insert that Guillain-Barré syndrome might be related to vaccination.

  39. Safety of Quadrivalent Meningococcal Conjugate Vaccine in 11- to 21-Year-Olds. 2017, Tseng, Pediatrics

    The risk of Bell's palsy (facial paralysis) within 12 weeks of vaccination was 5 times higher for those who received the meningococcal vaccine (Menactra/Menveo) together with other vaccines, as compared to the control group. However, patients vaccinated with the same vaccines over 12 weeks before, were used as a control group.
    The risk of Hashimoto’s disease was 5.5 times higher among those vaccinated, the risk of iridocyclitis was 3.1 times higher, and the risk of epileptic seizure was 2.9 times higher. All these cases were later reviewed, some of them were excluded, and the authors concluded that there was no statistically significant relationship between the vaccine and these diseases.

  40. Safety of a quadrivalent meningococcal serogroups A, C, W and Y conjugate vaccine (MenACWY-CRM) is administered with routine infant vaccinations: results of an open-label, randomized, phase 3b controlled study in healthy infants. 2014, Abdelnour, Vaccine

    Clinical trials of the Menveo vaccine. 5,700 patients received Menveo and other vaccines (DTaP/IPV/Hib/MMR/PCV), and 2,000 patients only received the other vaccines.
    16% of infants vaccinated with Menveo and other vaccines, and 13% of infants vaccinated only with the other vaccines, showed serious systemic reactions. The authors played around with the statistics a bit, and concluded that there was no difference between the two groups, and that the vaccine is completely safe.
    Also, the group vaccinated against meningococcus had twice as many deaths, but these deaths had no connection to the vaccine whatsoever.
    Seven cases might have been related to the vaccine (Kawasaki syndrome, epilepsy, acute disseminated encephalomyelitis)

  41. Immunogenicity and safety of the multicomponent meningococcal B vaccine (4CMenB) in children and adolescents: a systematic review and meta-analysis. 2018, Flacco, Lancet

    The incidence of serious side effects, potentially associated with Bexsero, is 1 in 185 cases. It is 4.5 higher than the incidence of serious side effects from other vaccines (1 in 830 cases). More: [1]

  42. Aluminum hydroxide, another meningococcal vaccine or Japanese encephalitis vaccine, were used as placebo in Bexsero clinical trials. Serious adverse events were registered in 2.1% of those vaccinated. The vaccine does not protect against all serogroup B strains. Bexsero contains the largest amount of aluminum among all vaccines – 1,500 μg. Hepatitis B vaccine, for example, contains 250 μg.
    In clinical trials of Menactra for infants, the control group received pneumococcal, hepatitis A and MMRV vaccines. In clinical trials of the vaccine for children and adults, meningococcal polysaccharide vaccine was used as placebo.
    Serious adverse events were registered in 2%-2.5% of cases. Irritability was observed in 60% of infants, and loss of appetite in 30%. The vaccine might be associated with Bell's palsy, transverse myelitis, acute disseminated encephalomyelitis, and some other diseases.
    Significantly less antibodies developed in those vaccinated, when Menactra vaccine was given one month after the Daptacel vaccine, as compared to those vaccinated with Menactra one month prior to being vaccinated with Daptacel.

  43. 160 children have been vaccinated against meningococcus in Chad, after which 40 of them developed neurological complications.

  44. Meningitec (conjugate, against serogroup C) vaccine is used in France. At least 680 children were harmed by this vaccine. They sued the company, and their lawyer ordered a laboratory test of the vaccine. It turned out that it contains nanoparticles of heavy metals, such as titanium, lead and zirconium.

  45. When meningococcal vaccine was added to the national immunization schedule in 2006, meningococcal infection incidence was 1 in 250,000. Mortality rate was 1 in 2.5 million
    In 2015, the incidence rate was 1 in a million. In 2014, only 43 people died of meningococcus in the USA, 5 of them were children under 5 years of age. That is, meningococcal mortality rate was 1 in 7 million.
    For comparison, 1,015 people died of H.influenzae infection in 2015, and 3,350 people died of pneumococcus. This is despite the fact that they are vaccinated against.
    Meningococcal infection incidence in 2017 was 1 in 200,000 in Russia, 1 in 150,000 in Israel, 1 in 100,000 in Ukraine, 1 in 200,000 in Europe, but 1 in 10,000 among infants.

  46. The number of meningococcal death cases among children under 5 years of age in the USA. Meningococcal vaccination for children has still not been introduced, however, the mortality rate has decreased by more than 90% since the mid-90s.
    Sources: [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19].

  47. 153 deaths and 366 disability cases after meningococcal vaccination have been registered with VAERS.
    In 2016, 7 children under 3 years of age died after vaccination, and 15 became disabled. In the same year, 9 children under 5 years of age died from meningococcal infection. Given that only 1-10% of all cases are registered in VAERS, and that only children in high-risk groups are vaccinated, meningococcal vaccine probably kills more people than meningococcal infection.

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Hepatitis B
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Allergies and autoimmunity
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