We deal with vaccinations. Part 23. Meningococcus

2024 Author: Seth Attwood | [email protected]. Last modified: 2023-12-16 15:55

1. Meningococcus is the third type of bacteria that causes meningitis and bacteremia. The incidence of meningococcal disease is significantly lower than that of pneumococcal and haemophilus influenzae, but since the meningococcal vaccine is the newest licensed vaccine, meningococcus has become the biggest horror story of late.

2. CDC Pinkbook

There are 13 serogroups of meningococcus, but mainly five are responsible for invasive infections: A, B, C, W, Y. 60% of invasive infections in children are caused by serogroup B.

The lethality of invasive infection is 10-15%, and the lethality of meningococcemia (meningococcal sepsis) reaches 40%.

Risk factors are active and passive smoking, alcohol, tightness and asplenia (absence of a spleen).

98% of cases are sporadic, and only 2% are due to outbreaks.

The first polysaccharide vaccine appeared in 1974. Like other polysaccharide vaccines, it is not effective in infants.

The first meningococcal conjugate vaccine (Menactra) was licensed in 2005 for adolescents over 11 years of age. A second vaccine (Menveo) was licensed in 2010. Both protect against ACWY serogroups. It was expected that vaccines would be effective for 10 years, but later it turned out that the number of antibodies decreases after 3-5 years, and those vaccinated at 11 years old will no longer be protected at 16-21 years old, when the risk of meningococcal infection is higher. Therefore, in 2010 revaccination was added at 16 years old.

In 2006-10, the CDC reported 30 cases of the disease in those vaccinated. The mortality rate among them was the same as that of the unvaccinated.

In 2014-15, two serogroup B vaccines, Bexsero (GSK) and Trumenba (Pfizer), were licensed, but they have not yet been added to the immunization schedule.

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

The incidence of meningococcal disease is 1 in 300,000 in the United States, and an average of 1 in 100,000 in Europe.

Previously, it was believed that the highest incidence occurs in children from 6-24 months, but recent data indicate that infants under 6 months of age who have not received antibodies from the mother are most sick.

ACWY serogroup conjugate vaccines are not effective in infants.

Most cases of the disease occur in serogroup B, but since the capsule of this serogroup contains a molecule that is very similar to glycoproteins in the brain, polysaccharide vaccines from this serogroup, firstly, do not produce antibodies well, and secondly, they can lead to an autoimmune reaction from - for the mechanism of molecular mimicry. Therefore, vaccines have been developed based on outer membrane proteins. But since the proteins of the outer membrane of meningococcus are able to change antigens, this can lead to the ineffectiveness of the vaccine.

Because meningococcal disease is a very rare disease, all meningococcal vaccines have been licensed on the basis of immunogenicity (i.e., antibody levels), not clinical efficacy.

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

Between 1998 and 2007, the incidence of meningococcal disease decreased by 64%. On average, over these years, the incidence was 1 in 200 thousand, and by 2007, the incidence of meningococcus had decreased to 1 in 300 thousand.

The highest incidence was among infants under one year old (5 per 100 thousand). 50% of their cases are caused by serogroup B. And two thirds of cases in the first year of life occur in infants less than 6 months of age.

Blacks get sick 44% more often than whites.

The mortality rate of meningococcal infection was 11%, and it increased with age. Among the elderly, mortality was 24%, and among infants, 3-6%.

Most cases were observed in January and February, and least of all in August.

The authors conclude that, prior to vaccination, the incidence of meningococcal disease in the United States was at an all-time low, and that there was no significant decrease in incidence since vaccination began in adolescents who were vaccinated because only 32% were vaccinated.

(A motive that runs like a red thread in almost all studies. If after the start of vaccination there was no decrease in incidence, then this is because coverage was insufficient. And if there was a decrease, then this, of course, is the merit of vaccination, even if only 2% were vaccinated) …

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

The mortality rate of meningococcal disease in Scotland fell from 10.3% in 1946-61 to 1.2% in 1971-86. The incidence dropped from 7.9 to 5.3 per 100,000 children.

The incidence of hemophilic infection during this time increased by 4 times, while the mortality rate fell from 19.2% to 3%.

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

The incidence of bacterial meningitis in Belgium increased 10-fold between 1988 and 1993, mainly due to meningococcus. Immigrants and non-whites were sick more often.

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

As a result of asymptomatic colonization by meningococcus, antibodies are produced from it for several weeks.

Babies up to six months are protected by the mother's antibodies. The concentration of antibodies in the blood of infants is higher than in the blood of the mother.

Natural immunity is usually developed during childhood.

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

10% of the population are carriers of the meningococcal bacteria. Among children, less than 3% are infected, and among 15-24 year olds, 24-37% are infected. A high level of colonization is also observed in the army. For example, among Norwegian soldiers, more than 70% were carriers of meningococcus.

A recent study has shown that the number of carriers of meningococcus, which is determined by conventional methods (bacterial culture), may be underestimated. Using another method (immunohistochemistry), it was found that 45% were carriers of meningococcus, while only 10% of them had meningococcus detected by the conventional method.

Colonization of meningococcus produces antibodies for several weeks after infection, and may protect against disease.

Approximately 50% of the strains found in carriers were found to be capsule-free. Previously, it was believed that capsule-free strains are not pathogenic, but then it turned out that meningococci are able to turn on and off the production of capsules with a high frequency. There is evidence that the loss of the capsule enhances the ability of meningococci to colonize the nasopharynx and escape the body's defense systems. 1 more]

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

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

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

Outbreaks of meningococcal disease have often occurred among pilgrims in Mecca, which is why Saudi Arabia has introduced mandatory vaccinations for Hajj visa applicants. Thereafter, no outbreaks were observed.

Meningococcal disease is most common in the "African meningitis belt", which includes countries south of the Sahara. Most cases are reported during the dry season. However, there is not a single known case of tourist illness.

Every 6 weeks, the CDC investigates potential meningococcal infections on airplanes. However, only two such cases are known.

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

The risk of meningococcal infection in a child under 18 years of age is 3.8 times higher if the mother smokes.

Among adults, smoking increases the risk of meningococcal infection by 2.4 times, secondhand smoke by 2.5 times, and chronic disease by 10.8 times.

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

Passive smoking increases the risk of meningococcal infection by 2.2 times. When both parents smoke, the risk is 8 times higher. More: [1] [2] [3]

In Ghana, where meningococcal meningitis is much more common than in developed countries, wood-fired cooking increases the risk of the disease by 9 times.

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

If the parents only smoke outside the home, this does not reduce the level of nicotine in the hair of the children, which may indicate that smokers continue to exhale nicotine after smoking. This hints that the risk of meningococcal infection will not be reduced if smoking is banned only in certain places, such as houses, cars and hospitals, and a total ban is needed. But it is known that relatively few people quit smoking, so vaccination of children will probably be more effective. In addition, there is hope that children will be able to protect their smoking parents from meningococcus by means of herd immunity.

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

The risk of meningococcal infection in homosexuals is 4 times higher than in heterosexuals. HIV-infected homosexuals get meningococcal disease 10 times more often than uninfected homosexuals. 45% of meningococcal patients reported having multiple partners and engaging in anonymous sex.

Among homosexuals, 32% smoke (versus 18% of US adults) and 48% use drugs (versus 10% on average).

In New York, the risk of meningococcal infection among homosexuals was 50 times higher than the average, in Germany 13 times higher, in Paris 10 times higher, in Southern California 50 times higher.

24% of homosexuals are carriers of meningococcus, compared with 6% among heterosexual women. Among homosexuals who have recently had oral-anal contact, 43% were carriers.

Meningococcus was also found in 4.5% of homosexuals in the anal canal.

In 2016, a new strain of meningococcus was discovered that can be sexually transmitted.

The CDC reports that 57% of men over 16 years of age with meningococcal disease reported homosexual contact in 2016. More: [1] [2] [3] [4].

15. Invasive meningococcal disease among men who have sex with men. (ECDC, 2013)

Infection with HIV increases the risk of meningococcal infection by 11 times, and AIDS by 12 times.

In 2010, an outbreak of meningococcus among homosexuals began in New York. It has to do with mobile dating apps and visiting gay bars.

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

Intimate kissing with multiple partners increases the risk of meningococcal infection among adolescents by 3.7 times. Premature birth also increases the risk by 3.7 times. Preceding illness increased the risk 2.9-fold.

Attendance at religious ceremonies is associated with an 11-fold reduction in risk, and vaccinations with an 8-fold reduction in risk.

It reports that marijuana is associated with a 4.2-fold increase in the risk of meningococcal infection and a 3.3-fold increase in nightclub attendance. Attending picnics and dancing lowered the risk by 3-4 times.

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

University of Ohio meningococcal outbreak (13 cases). Going to bars was associated with an 8-fold increased risk of illness, and kissing with more than one partner 13.6-fold.

In Chile, risk factors for meningococcal disease were crowdedness (more than 2.5 people in the bedroom), low maternal education, low income, alcohol abuse and chronic illness.

In Brazil, low parental education is associated with a 2-fold increased risk of meningococcal colonization, which probably reflects socioeconomic conditions.

In Greece, crowding and previous acute respiratory infections increased the risk of the disease in children by 3 times, and smoking by the father by 4.5 times. More: [1] [2] [3]

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

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

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

In 1999, England introduced meningococcal (serogroup C) conjugate vaccine into the national immunization schedule for infants 2, 3 and 4 months of age. The effectiveness of the vaccine in the first year after vaccination was 93%, but after a year the effectiveness became negative (-81%). Immunity after vaccination at a later age lasts longer.

twenty. Effect of outer mempane vesicle vaccine against group B meningococcal disease in Norway. (Bjune, 1991, Lancet)

Norway has the highest incidence of meningococcal disease in Europe and 80% of cases are in serogroup B. (There was an epidemic in the 1970s / 80s and the incidence was 1 in 14-21,000).

A double-blind, randomized study (170,000 people) was conducted with the outer membrane protein vaccine (OMV). Aluminum hydroxide was used as a placebo.

The effectiveness of the vaccine was only 57%, so it was decided not to include it in the vaccination schedule.

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

Serogroup B vaccine clinical trial in Chile (40,000 people). A vaccine against other meningococcal serogroups was used as a placebo.

The vaccine efficacy over 2.5 years was 51%, and among children under 5 years of age, the efficacy was negative -23%.

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

In 1991, an epidemic of serogroup B meningococcus began in New Zealand. In 2001, it peaked and began to decline.

By 2004, a special vaccine had been developed for the New Zealand strain. Since it was considered unethical to conduct randomized trials during an epidemic, a vaccination campaign was launched in 2004 for all children 6 weeks to 19 years of age. By 2006, 80% of children had been vaccinated and the campaign was discontinued.

7 months after the third dose of the vaccine, the number of antibodies in the infants returned to almost the original level. 1 more]

Detailed journalistic investigation of this campaign: [1] [2]

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

Eculizumab is a very rare medicine that suppresses the complement system (a component of the innate immune system). This drug has been associated with a 1000 to 2000 fold increased risk of meningococcal infection.

16 people using this drug developed meningococcemia, of which 14 were vaccinated.

24. Factor H is one of the proteins that regulate the complement system. Being bound to a cell, factor H suppresses the reaction of the complement system against this cell, and when unbound, it enhances the same reaction against microorganisms. If the bacterium has a protein that can bind factor H to itself, then the bacterium can thus avoid the attack of the complement system. This mechanism is part of the virulence of some bacteria, including meningococcus.

Since previous types of serogroup B meningococcal vaccine (polysaccharide, conjugate and outer membrane vaccines) have proved ineffective, protein binding factor H has been added to newer vaccines (Bexero and Trumanba), in the hope that this will lead to higher efficacy.

Antibodies generated after Bexero vaccination in animals were cross-reactive with human factor H. It is not known at this time whether antibodies against factor H will be produced in humans, and whether this would increase the risk of an autoimmune reaction.

(Antibodies that cross-reactive with factor H can also lead to suppression of the complement system, which is key in the body's suppression of meningococcal infection.)

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

Just like pneumococcus, meningococcal bacteria can change their serogroup.

26. 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). (Law, 2006, J Clin Microbiol)

In 2004, there was an outbreak of serogroup B meningococcal disease in Quebec. The authors believe that this was probably due to a serogroup replacement due to vaccination with a polysaccharide vaccine for serogroup C.

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

In early 2015, there was an outbreak of serogroup B meningococcal infection at a college in Rhode Island (two cases). Both recovered.

In the aftermath of the outbreak, 5 three-dose vaccination campaigns were conducted for students and teachers on campus, as well as for their intimate partners. In total, ~ 4,000 people were vaccinated with the newly licensed Trumanba vaccine.

Since it was not known how this vaccine affects colonization, the authors used a vaccination campaign to test this.

20-24% were carriers of meningococcus and 4% were carriers of serogroup B.

Among smokers, the risk of colonization was increased by 30%, and among those who visit bars and clubs at least once a week, the risk of colonization was increased by 80%.

The authors concluded that vaccination does not affect the colonization of meningococcus or herd immunity in any way, and therefore a high vaccine coverage is required.

28. Meningococcal carriage among a university student population - United States, 2015. (peakwell, 2018, Vaccine)

A study of meningococcal colonization at another university in Rhode Island.

Vaccination had no effect on colonization.

Smoking increased the risk of colonization by 1.5 times, and visiting bars at least once a week - 2 times.

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

Following the outbreak, a vaccination campaign was launched at the University of Oregon. 11% -17% were carriers of meningococcus, of which 1.2% -2.4% were carriers of serogroup B.

Vaccination with 1-2 doses of Bexero and 1-3 doses of Trumenba did not affect the colonization of meningococcus in general, and the colonization of serogroup B in particular.

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

In England, adolescents have recently begun to be vaccinated with a conjugate vaccine (for serogroups ACWY). The authors tested colonization of meningococcus before and after vaccination at the university, and it turned out that despite vaccination coverage of 71%, colonization increased from 14% to 46%, and colonization by serogroup W increased 11-fold, from 0.7% to 8%.

31. Dr. Rodewald, director of vaccinations at the CDC, said in 2004 that the CDC is doing poorly with vaccinations for adolescents, and therefore intimidating parents about the consequences of not vaccinating children will be part of an advertising campaign. And that the meningococcal vaccine is ideal for these purposes. Because after the meningococcus vaccine, booster vaccinations against tetanus, diphtheria and pertussis, as well as HPV and herpes vaccines will also need to be added to the vaccination calendar.

The article also says that vaccination is usually much cheaper than the cost of treatment, but in the case of meningococcus, this is not the case. The vaccinations will cost $ 3.5 billion a year, and each life saved will be worth over a million dollars. More: [1 (p.13)]

32. Depressive symptoms and immune responses to meningococcal conjugate vaccine in early adolescence. (O'Connor, 2014, Dev Psychopathol)

Children who are depressed develop more antibodies after being vaccinated against meningococcus than non-depressed children.

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

Menaktra was licensed in January 2005 and has been recommended for 11-12 year olds as well as freshmen.

Among the vaccinated freshmen between June 10 and July 25, 2005, 5 cases of Guillain-Barré syndrome were reported at VAERS.

In one of the cases, the vaccinated girl already had Guillain-Barré syndrome twice before, at 2 and 5 years of age, both times within 2 weeks after vaccination.

The CDC concludes that this is possibly a coincidence and recommends that vaccinations be continued. The manufacturer added to the insert that Guillain-Barré Syndrome may be related to vaccination.

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

Among those who received the meningococcus vaccine (Menaktra / Menveo) along with other vaccines, the risk of facial paralysis within 12 weeks after the vaccination was 5 times higher than in the control group. True, the same vaccinated were used as a control group, only 12 weeks after vaccination and further.

The risk of Hashimoto's disease in those vaccinated was 5.5 times higher, iridocyclitis 3.1 times higher, and epileptic seizure 2.9 times higher. But then all these cases were revised, some of them were excluded, and the authors concluded that there was no statistically significant relationship between vaccination and these diseases.

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

Clinical trials of Menveo vaccine. 5700 received Menveo and other vaccines (DTaP / IPV / Hib / MMR / PCV), and 2000 received only other vaccines

Among infants vaccinated with the Menveo vaccine and other vaccines, serious systemic reactions were observed in 16%, and among those vaccinated with other vaccines only - in 13%. The authors played a little with statistics and concluded that there was no difference between the two groups, and the vaccine is completely safe.

Also, in the group vaccinated against meningococcus, there were twice as many deaths, but their deaths were in no way associated with vaccination.

Seven cases were possibly vaccine-related (Kawasaki syndrome, epilepsy, acute disseminated encephalomyelitis).

36. Bexsero clinical trials used aluminum hydroxide, another meningococcal vaccine, or Japanese encephalitis vaccine as a placebo.

Serious negative cases were reported in 2.1% of those vaccinated. The vaccine does not protect against all serogroup B strains. This vaccine contains the highest amount of aluminum of any vaccine at 1,500 mcg. The hepatitis B vaccine, for example, contains 250 mcg.

In the Menactra clinical trial for infants, the control group received vaccines against pneumococcus, hepatitis A and MMRV. In clinical trials of a vaccine for children and adults, a polysaccharide vaccine against meningococcus was used as a placebo.

Serious negative cases were reported in 2-2.5%. 60% of infants were irritable, 30% lost appetite.

The vaccine is possibly associated with facial paralysis, transverse myelitis and acute disseminated encephalomyelitis and several other diseases.

When Menaktru was given a month after the Daptsel vaccine, the vaccinated had significantly fewer antibodies than those vaccinated a month before the Daptsel vaccination.

37. In Chad, 160 children were vaccinated against meningococcus, after which 40 developed neurological complications.

38. In France, the Meningitec vaccine (conjugated from serogroup C) is used. At least 680 children have been affected 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.

39. In 2006, when the meningococcal vaccine was added to the national immunization schedule, the incidence of meningococcal disease was 1 in 250,000. The death rate was 1 in 2.5 million.

In 2015, the incidence was 1 per million. In 2014, only 43 people died of meningococcus in the United States, of which 5 are children under 5. That is, the death rate from meningococcus was 1 in 7 million.

For comparison, in 2015, 1,015 people died from hemophilus influenzae, and 3,350 people died from pneumococcus. And this despite the fact that they are vaccinated against.

The incidence of meningococcal disease in 2017 in Russia is 1 in 200,000, in Israel 1 in 150,000, in Ukraine 1 in 100,000, in Europe 1 in 200,000, but among infants 1 in 10,000.

40. Number of deaths from meningococcus among children under 5 years of age in the United States. Vaccination against meningococcus for children has not yet been introduced, however, mortality has dropped by more than 90% since the mid-90s.

I have often written that it is estimated that 1-10% of all side effects are reported in VAERS. What is this statement based on?

41. Introducing MEDWatch. A new approach to reporting medication and device adverse effects and product problems. (Kessler, 1993, JAMA)

Between 3% and 11% of hospital admissions can be the result of drug side effects. Only 1% of serious side effects are reported to the FDA.

This leads to the fact that problems with drugs are not detected in time. For example, although silicone implants have been on the market for 30 years, it has only recently been found that they are associated with autoimmune diseases.

42. Limitations and strengths of spontaneous reports data. (Goldman, 1998, Clin Ther)

In the UK, it is estimated that no more than 10% of serious side effects are reported, and 2% -4% of non-serious drug side effects.

The FDA receives fewer than 1% of suspected serious side effects.

The peak of reported side effects occurs at the end of the second year of the drug's on the market, after which the number of reports decreases, although the number of side effects does not change.

43. The reporting sensitivities of two passive surveillance systems for vaccine adverse events. (Rosenthal, 1995, Am J Public Health)

In VAERS, 72% of cases of vaccine-associated polio were reported, but only 4% of cases of hypotonic-hyporesponsive episode after DTP, and less than 1% of cases of thrombocytopenia after MMR. The consequences that occur long after vaccination, and the consequences that are not usually associated with vaccination, are much less common.

It reports that less than 5% of VAERS reports come from parents.

44. VAERS reported 153 deaths following meningococcal vaccination and 366 disabilities.

In 2016, 7 children under the age of 3 died after being vaccinated, and another 15 became disabled. In the same year, 9 children under 5 died of meningococcus. With VAERS accounting for only 1-10% of all cases, and that only children at risk are vaccinated, meningococcus vaccine is likely to kill more people than meningococcus.