If I were to remain silent, I'd be guilty of complicity.
Albert Einstein
13-12-2017 15:01
Translated from Russian by: Elizaveta Milashevich
  1. Pneumococcus is a common bacterium that, like Haemophilus influenzae, can lead to meningitis and other invasive diseases. After the start of Hib vaccination, the incidence of Haemophilus influenzae temporarily decreased, and the incidence of pneumococcal infection increased. However, if the mortality rate from Haemophilus influenzae meningitis is 3%, the mortality rate from pneumococcal meningitis is 19%.

  2. CDC Pinkbook

    Pneumococcus (Streptococcus pneumoniae) lives in the nasopharynx of 5%-90% of healthy people. Among schoolchildren, the bacterium is found in 20%-60% of cases, among soldiers - in 50%-60%, and among childless adults - in 5%-10%.
    The relationship between pneumococcal colonization and natural immunity is poorly understood.
    Streptococcus pneumoniae can lead to pneumonia, bacteremia, and meningitis. Accurate statistics on pneumococcus are not maintained, but it is estimated that 400,000 people are diagnosed with pneumococcal pneumonia (fatality 5%-7%), 12,000 with bacteremia (fatality 20%, and 60% among the elderly), and 3,000-6,000 with meningitis each year (fatality 8% among children and 22% among adults).
    Risk factors for invasive pneumococcal infection include smoking, leukemia, HIV and other immunodeficiencies, lack of spleen, presence of cochlear implants, renal failure, liver disease, and other chronic diseases. The risk of invasive infection is also increased among Alaska natives, Black people, and some Indian tribes.
    With a decrease in the incidence of Hib, pneumococcus has become the main cause of bacterial meningitis among children under 5 years of age in the United States.
    There are 92 serotypes of pneumococcus. The 10 most common serotypes are responsible for 62% of invasive diseases.
    The first pneumococcal conjugate vaccine was licensed in 2000, and included 7 serotypes (PCV7). In 2010, a vaccine against 13 serotypes (PCV13) was licensed. There is also a 23-valent polysaccharide pneumococcal vaccine (licensed in 1983) that is used today for the elderly.
    The pneumococcal immunity to penicillin and other antibiotics was very common, but after the start of PCV7 vaccination, it decreased and then increased again. Then, in 2008, the definition of penicillin immunity was changed, and today it is believed that most strains are susceptible to penicillin. Clinical resistance to penicillin was found to be different from in vitro susceptibility.
    The vaccine contains aluminum and polysorbate 80.

  3. Risk Factors

  4. Risk Factors for Invasive Pneumococcal Disease in Children: A Population-based Case-Control Study in North America. 1999, Levine, Pediatrics

    Breastfeeding is associated with a 73% reduction in the risk of pneumococcal infection.
    The risk of hospitalization of not breastfed children due to pneumonia (not only pneumococcal) was 17 times higher than for breastfed children. Among infants younger than 3 months it was 61 times higher.

  5. Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team. 2000, Nuorti, N Engl J Med

    Smoking is associated with a 4.1-fold increase in the risk of invasive pneumococcal infection in adults, passive smoking – with a 2.5-fold increase.
    Chronic disease is associated with a 2.6-fold increase in risk. People with incomplete secondary education get the disease 2.8 times more often, and people with secondary education twice as often than people with higher education.

  6. The influence of chronic illnesses on adults with invasive pneumococcal disease in adults. 2005, Kyaw, J Infect Dis

    The risk of an adult healthy person getting an invasive pneumococcal infection is 8.8 per 100,000. Most cases are elderly people. Diabetes increases the risk by 3.4 times, chronic heart disease - by 6.4 times, chronic lung disease - by 5.6 times, cancer - 23 times, AIDS - 48 times, blood cancer - 38 times, alcoholism - 11 times. The risk of a chronic patient dying from pneumococcal infection is increased 2.8 times.
    Healthy black people get the disease 2.3 times more often than healthy white ones. Black people who are also alcoholics get it 6 times more often than white ones.

  7. Risk factors for primary invasive pneumococcal disease among children in Finland. 1995, Takala, JAMA

    Kindergarten is associated with an increase in the risk of pneumococcal infection among children under 2 years of age by 36 times, and the risk of frequent otitis media - with 9-fold increase.

  8. Geographical differences in invasive pneumococcal disease rates and serotype frequency in young children. 2011, Hausdorff, Lancet

    In the USA, the incidence of invasive pneumococcal infection among children under 6 years old is 3-6 times higher than in Europe. It is also higher than in Australia and New Zealand.
    This is most likely because in the United States they take blood for bacterial analysis from all children under 3 years old with a temperature of 39 and above, and from everyone who has elevated white blood cells (they are also given antibiotics), and in Europe a similar analysis is usually done only for hospitalized patients. Since most cases of invasive pneumococcal infection are temporary bacteremia that do not require hospitalization, they are, for the most part, not diagnosed in European countries.

  9. Association between a priori antibiotic therapy and subsequent risk of community-acquired infections: a systematic review. 2017, Malik, J Antimicrob Chemother

    The use of antibiotics subsequently increases the risk of pneumococcal infection, as well as the risk of Hib, meningitis, infections with Staphylococcus aureus, Salmonella and Campylobacter, typhoid fever, boils, mastitis, acute respiratory infections, and urinary tract infections.

  10. Invasive pneumococcal disease in Dallas County, Texas: results from population-based surveillance in 1995. 1998, Pastor, Clin Infect Dis

    People with low income suffer from pneumococcus 2 times more often than people with middle income, and 3 times more often than people with high income.

  11. Invasive pneumococcal infection in Baltimore, Md: implications for immunization policy. 2000, Harrison, Arch Intern Med

    Black people get pneumococcus 3.3 times more often than white people, and 40-49-year old Black people - 12 times more often. The median age of patients among blacks is 27 years lower than among whites.
    Low-income people get sick more often. Urban dwellers are sick more often than suburban residents.
    Almost 50% of infected blacks are infected with HIV. AIDS increases the risk of pneumococcal infection by 100-300 times.
    The authors conclude that it is necessary to vaccinate young and poor people living in cities. Despite the fact that pneumococcus is mainly registered in blacks, it is necessary to vaccinate whites too since there are also poor people among whites. Since vaccination of exclusively risk groups was tested with hepatitis B and failed, the authors believe that universal vaccination against pneumococcus is necessary.

  12. Pneumococcus and Haemophilus influenzae

  13. Increase in bacteraemic pneumococcal infections in children. 1995, Baer, Lancet

    Between 1992 and 1994, the incidence of pneumococcus in Finland increased by 2 fold among children under two years old, and 3 times among children under 16 years old. The authors attribute this to the disappearance of Hib.

  14. Invasive pneumococcal infection in South and West England. 1998, Smith, Epidemiol Infect

    Between 1982 and 1992, the incidence of pneumococcal bacteremia and meningitis in England rose 2.3 times.

  15. Increase in pneumococcal bacteraemia in Sweden. 1997, Giesecke, Lancet

    Between 1990 and 1995, the incidence of pneumococcal bacteremia among adults in Sweden rose 2.6 times. The same thing was observed in Norway.

  16. Clinical Characteristics of Children With Complicated Pneumonia Caused by Streptococcus pneumoniae. 2002, Tan, Pediatrics

    In 1994, 22.6% of pneumococcal pneumonia in the United States was accompanied by complications. In 1999, there were already 53% of pneumonia with complications.

  17. Rising rate of pneumococcal bacteremia at the Children's Hospital of Philadelphia. 1994, Foster, Pediatr Infect Dis J

    During five years after the start of Hib vaccination, the incidence of pneumococcal bacteremia in Philadelphia doubled (from 38 to 73 cases per year). The incidence of hemophilic bacteremia has decreased from 34 to 9 cases per year, and the incidence of meningococcal bacteremia has not changed (3 cases per year).
    The incidence of pneumococcal meningitis increased by 50% (from 5.2 to 7.6 cases per year). The incidence of H. influenzae meningitis has decreased from 18 to 5.6 cases per year, and the incidence of meningococcal meningitis has not changed (3 cases per year).

  18. Inhibitory and Bactericidal Effects of Hydrogen Peroxide Production by Streptococcus pneumoniae on Other Inhabitants of the Upper Respiratory Tract. 2000, Pericone, Infect Immun

    In vitro, pneumococcus has a bactericidal effect on the H. influenzae bacteria. Pneumococcus secretes hydrogen peroxide, which kills the H. influenzae. Pneumococcus also has an inhibitory effect on the meningococcus, which also dies when exposed to hydrogen peroxide, although this requires a higher concentration.
    The production of hydrogen peroxide by pneumococcus correlates with the concentration of oxygen in the environment. Other bacteria that secrete hydrogen peroxide are lactobacilli and oral streptococci.
    The bacteria that hydrogen peroxide kills or inhibits are Staphylococcus aureus, Gonococcus (a bacterium that causes gonorrhea) and diphtheria.

  19. The Role of Innate Immune Responses in the Outcome of Interspecies Competition for Colonization of Mucosal Surfaces. 2005, Lysenko, PLoS Pathog

    Although in vitro pneumococcus kills H. influenzae, in vivo in mice it turned out the opposite. Despite the fact that pneumococcus and H. influenzae live separately in the nasopharynx, in case of joint colonization, pneumococcus quickly disappears, and only the H. influenzae remains. It turns out that H. influenzae somehow affects neutrophils (a type of phagocyte), which kill pneumococcal bacteria. Neutrophils alone do not kill pneumococci as effectively as in the presence of a H. influenzae. How exactly H. influenzae affects neutrophils is still unknown.
    The authors conclude that manipulations such as antibiotics or vaccines that are designed to eliminate one pathogen can inadvertently alter the competitive interactions of complex microbial communities.

  20. Pneumococcus and Staphylococcus aureus

  21. Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. 2004, Bogaert, Lancet

    A clinical study of pneumococcal vaccine in the Netherlands found that colonization with vaccine serotypes of pneumococcus negatively correlates with colonization with Staphylococcus aureus. No correlation was found between non-vaccine serotypes and Staphylococcus aureus.
    The risk of acute otitis media caused by Staphylococcus aureus increased after vaccination.

  22. Association between carriage of Streptococcus pneumoniae and Staphylococcus aureus in children. 2004, Regev-Yochay, JAMA

    Another study in Israel also found that colonization of pneumococcus, especially vaccine serotypes, negatively correlates with colonization of Staphylococcus aureus in children.

  23. Interference between Streptococcus pneumoniae and Staphylococcus aureus: In vitro hydrogen peroxide-mediated killing by Streptococcus pneumoniae. 2006, Regev-Yochay, J Bacteriol

    Pneumococcus released hydrogen peroxide also kills Staphylococcus aureus.

  24. Effect of seven-valent pneumococcal conjugate vaccine on Staphylococcus aureus colonisation in a randomized controlled trial. 2011, van Gils, PLoS One

    After pneumococcal vaccination, a temporary increase in the colonization of Staphylococcus aureus is observed.

  25. Seven-Valentine Pneumococcal Conjugate Vaccine and Nasopharyngeal Microbiota in Healthy Children. 2014, Biesbroek, Emerg Infect Dis

    In those who got pneumococcal vaccines, there are fewer pneumococcal bacteria of non-vaccine serotypes in the upper respiratory tract, but more H. influenzae and staphylococcus, as well as much more anaerobic bacteria. Some of these bacteria are known to increase the risk of otitis media. Temporary bacterial imbalance also increases the risk of otitis media.
    Those taking antibiotics had 4 times fewer corynebacteria and Dolosigranulum, but 6.3 times more staphylococcus.

  26. Microbial interactions during upper respiratory tract infections. 2008, Pettigrew, Emerg Infect Dis

    Colonization with pneumococcus negatively correlates with colonization with H. influenzae, and with Staphylococcus aureus colonization.
    The authors conclude that elimination of pneumococcus and Haemophilus influenzae due to vaccination may increase the risk of otitis media due to colonization with Staphylococcus aureus, that the effects of this public health intervention can be difficult to predict, and that caution should be exercised in developing strategies to control colonization of the upper respiratory tract.

  27. The epidemiology, treatment, and prevention of transmission of methicillin-resistant Staphylococcus aureus. 2011, Calfee, J Infus Nurs

    MRSA - methicillin-resistant staphylococcus aureus, also called superbug, is an intractable infection that is resistant to most antibiotics. Until the 1980s, it was rarely registered, in the 1980s you could only get infected in hospitals, and in the 1990s you could already get infected outside of hospitals.
    Each year, about 11,000 Americans die from Staphylococcus aureus, and 5,500 die from MRSA. 3 times fewer people die from pneumococcus.

  28. Production of Hydrogen Peroxide by Bacteria. 1922, McLeod, Biochem J

    The fact that pneumococcus secretes hydrogen peroxide, and thus has an antiseptic effect in relation to Staphylococcus aureus and other bacteria, was established back in 1922. Streptococcus also emits hydrogen peroxide.
    By the way, streptococci in saliva, due to the release of hydrogen peroxide, also inhibit diphtheria bacterium.

  29. Bacterial antagonism, with particular reference to meningococcus. 1915, Colebrook, Lancet

    In 1915, it was found that pneumococcus in the upper respiratory tract completely suppresses meningococcus and other bacteria. Streptococcus also suppresses meningococcus.
    The author states that antiseptics are not always effective against meningococcus, because they do not gain access to all bacteria, and it will be more effective to implant a colony of pneumococcal bacteria to meningococcal carriers. The author performed this procedure on his colleague and five other volunteers. Despite the large numbers of implanted bacteria, they did not take root in five volunteers and did not suppress meningococcus. But in the sixth case they took root and completely suppressed meningococcus, though the effect lasted only two days.

  30. Efficiency

  31. The pneumococcal vaccine after 15 years of use. 1994, Hirschmann, Arch Intern Med

    The pneumococcal polysaccharide vaccine was licensed in the US in 1977. It is usually received by the elderly, various chronic patients and other risk groups (for example, Indians).
    The authors analyze all published studies and conclude that there is no evidence that this vaccine is effective for any population.
    The FDA licensed the vaccine based on studies from the 1930s and 1940s, studies from South African gold mines and mountaineers from New Guinea. Randomized trials published after licensing showed zero efficacy. The vaccine is least effective for those risk groups for which it is intended - elderly and immunodeficient patients. Although revaccination is recommended after 6 years, there is no evidence that the second dose is more effective than the first. More: [1], [2].

  32. Trends in invasive pneumococcal disease-associated hospitalizations. 2006, Shah, Clin Infect Dis

    After vaccination began, the incidence of pneumococcal bacteremia significantly decreased among the elderly, and only slightly among children. The incidence of pneumococcal meningitis fell 3 times.
    This is what the authors report in the abstract. What they are not focusing on is that the total number of cases of bacterial meningitis has not changed, and the number of cases of bacteremia has only increased.

  33. Empyema Hospitalizations Increased in US Children Despite Pneumococcal Conjugate Vaccine. 2010, Li, Pediatrics

    Pleural empyema is a complication of pneumonia (accumulation of pus in the cavities surrounding the lungs), which occurs in 3% of cases of pneumonia, and in a third of cases of pneumococcal pneumonia.
    The incidence of pleural empyema in the United States increased by 70% between 1997 and 2006, despite a decrease in cases of bacterial pneumonia and pneumococcus. Among children under 5 years of age, hospitalization due to pleural empyema increased by 100%.
    The incidence of bacterial pneumonia decreased by 13%. The incidence of invasive pneumococcus has decreased by 50%. The total number of pneumonia complications increased by 44%.

  34. Since the start of vaccination against pneumococcus in France, the number of cases of pneumococcal meningitis has increased by 34% (from 0.93 to 1.25/100,000).

  35. Pneumococcal responses are similar in Papua New Guinean children aged 3-5 years vaccinated in infancy with pneumococcal polysaccharide vaccine with or without prior pneumococcal conjugate vaccine, or without pneumococcal vaccination. 2017, van den Biggelaar, PLoS One

    The number of antibodies from pneumococcus did not differ in unvaccinated and vaccinated with conjugated or polysaccharide vaccines. (Papua New Guinea)

  36. Efficacy of an 11-valent pneumococcal conjugate vaccine against radiologically confirmed pneumonia among children less than 2 years of age in the Philippines: a randomized, double-blind, placebo-controlled trial. 2009, Lucero, Pediatr Infect Dis J

    In the Philippines, the conjugate pneumonia vaccine was 23% effective, and the efficiency of very serious pneumonia was -27% (no statistical significance).
    The vaccinated showed 2.4 times more serious negative cases in general, and 3.6 times more serious negative cases from pneumonia, compared with the placebo group.

  37. Strain replacement

  38. Rapid pneumococcal evolution in response to clinical interventions. 2011, Croucher, Science

    In response to antibiotics and vaccination, pneumococcus mutates rapidly. Pneumococcal bacteria can change their serotype.

  39. Emergence of Multidrug-Resistant Pneumococcal Serotype 35B among Children in the United States. 2017, Olarte, J Clin Microbiol

    After the beginning of vaccination, a new serotype 35B appeared, which had been rarely seen before, but now it is responsible for an increasing number of pneumococcal infections. This serotype is 5 times more deadly than other serotypes, and is often insensitive to antibiotics.
    The incidence of pneumococcus decreased by 2 times within two years after the introduction of vaccination, and remained at about the same level. More: [1].

  40. Emergence of invasive pneumococcal disease caused by nonvaccine serotypes in the era of 7-valent conjugate vaccine. 2008, Muñoz-Almagro, Clin Infect Dis

    After the start of vaccination, the incidence of pneumococcal infection in Barcelona increased by 58%, and among children - by 135%.
    The incidence of vaccine serotypes decreased by 40%, and for non-vaccine serotypes it increased by 531%.
    The incidence of pneumonia and empyema among children under 5 years of age increased by 320%.

  41. Temporal trends of invasive disease due to Streptococcus pneumoniae among children in the intermountain west: the emergence of nonvaccine serogroups. 2005, Byington, Clin Infect Dis

    After vaccination began, between 1997 and 2003, the incidence of pneumococcal infection in Salt Lake City (Utah) decreased by 27%. The incidence of vaccine serotypes decreased from 73% to 50%. The number of cases from non-vaccine serotypes increased 3 times. Children with non-vaccine serotypes were hospitalized longer. The proportion of cases of pleural empyema complications increased from 16% to 30%, and the proportion of severe cases increased from 57% to 71%. More: [1].

  42. Invasive pneumococcal disease caused by nonvaccine serotypes among Alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage. 2007, Singleton, JAMA

    Native children in Alaska suffer from invasive pneumococcal infection 3 times more often than Americans on average. In the first 3 years after the start of vaccination (2001-2003), the incidence of pneumococcal infection among indigenous children under 2 years old in Alaska decreased by 67%. After that, in 2004-2006, the incidence increased by 82%.
    The incidence of vaccine serotypes decreased by 96%, and for non-vaccine serotypes it increased by 140%.
    The proportion of cases complicated by pleural empyema increased from 2% to 13%. The proportion of cases with pneumonia and bacteremia increased from 40% to 57%.
    In 2004, 41% of the population were carriers of pneumococcus. The proportion of seven vaccine serotypes decreased from 41% to 5%, and for non-vaccine serotypes it increased from 47% to 88%.

  43. The epidemiology of invasive pneumococcal disease in British Columbia, the next implementation of an infant immunization program: increases in herd immunity and replacement disease. 2012, Sahni, Can J Public Health

    The incidence of invasive pneumococcal infection among children under 5 years old decreased by 78% between 2002 and 2010, but it increased among children over 5 years old, adults and the elderly. Vaccine strains were replaced by non-vaccine ones. In general, the incidence has not changed. In 2006-2007, an outbreak of pneumococcus was recorded among beggars and drug addicts. (British Columbia, Canada)

  44. Routine pneumococcal vaccination of children provokes new patterns of serotypes causing invasive pneumococcal disease in adults and children. 2013, Norton, Am J Med Sci

    The incidence of invasive pneumococcal infection among children decreased by 2 times between 1996 and 2010, but among adults it increased by a third. In general, the incidence increased slightly. (Huntington, West Virginia).

  45. Rebound in the incidence of pneumococcal meningitis in northern France: effect of serotype replacement. 2010, Alexandre, Acta Paediatr

    The incidence of pneumococcal meningitis among children under 18 years old increased 2.2 times between 2005 and 2008. The incidence among children under 2 years old increased by 6.5 times. Vaccination coverage over this time increased from 56% to 90%.
    In 2008, the incidence of pneumococcal meningitis reached the same level as in the pre-vaccination era. (Northern France)

  46. Initial Effects of the National PCV7 Childhood Immunization Program on Adult Invasive Pneumococcal Disease in Israel. 2014, Regev-Yochay, PLoS One

    Two years after the introduction of vaccination, the incidence of invasive pneumococcal infections among adults in Israel has not changed.

  47. The changing role of exposure to children as a risk factor for bacterial pneumococcal disease in the post conjugate vaccine era. 2010, Metlay, Arch Intern Med

    In Philadelphia, the incidence of vaccine serotypes among adults decreased by 29% per year in 2002-2008, and non-vaccine serotypes increased by 13% per year. In general, the incidence of pneumococcal infection increased by 7% per year.

  48. All studies show a decrease in the incidence of vaccine serotypes and an increase in the incidence of non-vaccine serotypes, but there are also studies according to which, despite the replacement of strains, the overall incidence of pneumococcus (or the incidence in some populations) decreased: [1], [2], [3], [4], [5].

  49. 44. A few more articles on the replacement of pneumococcal strains from vaccine to non-vaccine: [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]
    ... and the replacement of pneumococcus with H. influenzae and other bacteria: [1], [2], [3], [4], [5], [6], [7].

  50. Colonization

  51. Carriage of pneumococci after pneumococcal vaccination. 1996, Obaro, Lancet

    Since invasive infection requires colonization of bacteria in the nasopharynx, the goal of vaccination is also to reduce the colonization of pneumococcus.
    The pneumococcal conjugate vaccine was first tested on infants in Gambia in 1993, where it was found that while vaccine serotype colonization decreased by 78%-89%, non-vaccine serotype colonization increased by 4.5 times.

  52. Carriage of Haemophilus influenzae is associated with pneumococcal vaccination in Italian children. 2015, Camilli, Vaccine

    Pneumococcus colonization among vaccinated and unvaccinated people in Italy did not differ. The H. influenzae bacteria were more often found among vaccinated ones.

  53. Effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae among children in São Paulo, Brazil. 2016, Brandileone, Vaccine

    After the start of vaccination, the colonization of vaccine serotypes decreased significantly, but it increased for non-vaccine ones. H. influenzae bacteria were found in vaccinated people 2-5 times more often than in unvaccinated ones. (Sao Paulo, Brazil)

  54. Post-PCV7 changes in the colonization of pneumococcal serotypes in 16 Massachusetts communities, 2001 and 2004. 2005, Huang, Pediatrics

    Between 2001 and 2004, in children under the age of 7 in Massachusetts, colonization with seven vaccine serotypes of pneumococcus in the nasopharynx decreased, and colonization with other serotypes increased. In general, the colonization of pneumococcus has not changed. Penicillin resistance increased from 8% to 25% among non-vaccine serotypes, and from 45% to 56% among vaccine serotypes.

  55. Continued impact of pneumococcal conjugate vaccine on carriage in young children. 2009, Huang, Pediatrics

    Continuation of the previous study. By 2007, vaccine serotypes had virtually disappeared, and were replaced by non-vaccine and penicillin insensitive serotypes. In general, the level of pneumococcal colonization remained at 30%, but it has grown significantly among children under 6 months of age.

  56. Impact of 13-Valent Pneumococcal Conjugate Vaccination on Streptococcus pneumoniae Carriage in Young Children in Massachusetts. 2014, Lee, J Pediatric Infect Dis Soc

    The 13-valent vaccine (PCV13) also did not change the colonization of pneumococcus. Colonization of vaccine serotypes decreased, while colonization of non-vaccine serotypes increased by 12% per year.
    The level of colonization among PCV13 vaccinated and unvaccinated children did not differ.
    Colonization with PCV13 strains was 70% lower among healthy vaccinated children, but not among children with ARI.

  57. Changes in nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis among healthy children attending a day-care center before and after the official financial support for the 7-valent pneumococcal conjugate vaccine and H. influenzae type b vaccine in Japan. 2014, Oikawa, J Infect Chemother

    In Japan, after the start of vaccination against Hib and pneumococcus, the colonization of vaccine serotypes of pneumococcus decreased, and colonization of non-vaccine serotypes increased. In general, colonization of pneumococcus has not changed. Colonization with a H. influenzae increased.

  58. Effect of Pneumococcal Conjugate Vaccination on Serotype-Specific Carriage and Invasive Disease in England: A Cross-Sectional Study. 2011, Flasche, PLoS Med

    In England, colonization of vaccine serotypes decreased, while colonization of non-vaccine serotypes increased. In general, colonization increased by 6% (no statistical significance).

  59. Effect of pneumococcal vaccination on nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in Fijian children. 2012, Dunne, J Clin Microbiol

    In Fiji, vaccination did not affect the colonization of pneumococcus.
    In Papua New Guinea, vaccination immediately after birth did not affect the colonization of pneumococcus.

  60. Acute otitis media (AOM)

  61. Changes in frequency and pathogens causing acute otitis media in 1995-2003. 2004, Casey, Pediatr Infect Dis J

    Between 1995 and 2003, the incidence of AOM did not change, but the incidence of protracted AOM decreased from 16% to 12%. Pneumococcus in cases of AOM was replaced by H. influenzae, which after the onset of pneumococcal vaccination became the main causative agent of the disease. (Rochester, New York)

  62. Predominance of nontypeable Haemophilus influenzae in children with otitis media following introduction of a 3+0 pneumococcal conjugate vaccine schedule. 2011, Wiertsema, Vaccine

    Pneumococcus and H. influenzae are responsible for 80% of cases of AOM. M. catarrhalis is responsible for 3-20% of cases. After the start of vaccination against pneumococcus, most cases of AOM are caused by nonencapsulated serotypes of H. influenzae.

  63. Effect of conjugate pneumococcal vaccine followed by polysaccharide pneumococcal vaccine on recurrent acute otitis media: a randomised study. 2003, Veenhoven, Lancet

    A randomized, double-blind study of the effect of pneumococcal vaccine on AOM in children older than 1 year who are prone to it. Hepatitis B and hepatitis A vaccines were used as a placebo.
    The incidence of AOM in vaccinated individuals was increased by 25%, although the statistical significance was borderline (CI 0.99-1.57). In children older than 2 years, the vaccine increased the risk of AOM by 45%. In children not too prone to otitis media, the vaccine increased the risk by 66%. Vaccination did not affect the colonization of pneumococcus, since vaccine serotypes were replaced by non-vaccine ones. In children vaccinated against pneumococcus, more Staphylococcus aureus was detected.

  64. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. 2001, Eskola, N Engl J Med

    Another randomized, double-blind study of the effect of pneumococcal vaccine on acute otitis media. Hepatitis B vaccine was used as a placebo.
    The vaccine reduced the incidence by 6%, but there was no statistical significance (CI -4 - 16).
    One child died, but his death was defined as unrelated to the vaccine.

  65. Effect of pneumococcal conjugate vaccine on nasopharyngeal bacterial colonization during acute otitis media. 2006, Revai, Pediatrics

    The previous study is widely cited, and it is not necessary to even mention that statistical significance was absent. It is also not necessary to mention other studies where the incidence of otitis media in vaccinated individuals has been increased.
    In addition, it is reported that the colonization of pneumococcus during otitis media has not changed, since vaccine serotypes have been replaced by non-vaccine ones.
    The bacterium M. catarrhalis was found more often in the middle ear in vaccinated children, compared with unvaccinated ones.
    Of the three types of bacteria (pneumococcus, hemophilic bacillus and M. catarrhalis), an average of 1.37 bacterial species were found in unvaccinated, 1.48 in partially vaccinated, and 1.67 in vaccinated.

  66. Moraxella catarrhalis: from Emerging to Established Pathogen. 2002, Verduin, Clin Microbiol Rev

    Previously, M. catarrhalis was considered a harmless bacterium, but in the last decade it suddenly turned out that it can lead to meningitis, sepsis, otitis media, pneumonia and other invasive diseases.
    Scientists are working on a vaccine.

  67. Miscellaneous

  68. Cerebrospinal fluid and plasma levels of vitamin C in children. 1985, Heinz-Erian, Padiatr Padol

    The concentration of vitamin C in the cerebrospinal fluid is 2.5-3 times higher than in the blood. In premature and full-term infants - it is 16 times higher. In premature infants, the concentration of vitamin C is 4-5 times higher than in schoolchildren.
    The level of vitamin C in the cerebrospinal fluid in patients with acute bacterial meningitis was significantly reduced.

  69. Like H. influenzae, pneumococcus is an opportunistic infection. That is, this bacterium itself is harmless, but in case of immunodeficiency, it becomes dangerous.

  70. Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b. 2012, Sun, JAMA

    The DTaP-IPV-Hib vaccine increases the risk of febrile seizures 4-7 times in the day of vaccination. When it is done together with the pneumococcal vaccine, the risk is increased in the foloowing 3 days. The risk of epilepsy does not increase.
    The pneumococcus vaccine (PCV7) is the most reactogenic of all currently used ones.

  71. Vaxxed bus - it was a bus that travels all over the United States, and collected thousands of testimonies from parents whose children were vaccinated. I usually don’t bring testimonies from there, but in this case I can’t resist.
    Triplets (two boys and a girl) got pneumococcal vaccine. On the same day, all three became autistic.

  72. Since 2000, 1577 deaths from pneumococcal vaccine have been reported to VAERS. 12,552 were hospitalized and 1,370 became disabled.

  73. In a confidential report that Pfizer provided to the European Medicines Agency, among other things, it is reported that:
    1) In the first half of 2011, 22 deaths were recorded after the PCV13 vaccine. In the vast majority of cases, death occurred shortly after vaccination.
    2) In two years (7/2009-7/2011), 1691 cases of adverse events were recorded, of which 18% were neurological. Among children who received only Prevenar-13, 9% of the adverse events were neurological. Among those who received Prevenar-13 along with another vaccine, 21% of the adverse events were neurological. Among those who received Prevenar-13 with Infanrix Hexa, 34% of the adverse events were neurological.

  74. Another confidential report that Wyeth (subsequently Pfizer) provided to the European Medicines Agency which analyzes the clinical trials of the 13-valent vaccine reports:
    1) Prevenar 13 clinical safety studies included 1,365 children. Of these, 493 infants and 287 children received the tested vaccine. Only 580 of them were observed for 6 months after vaccination. A 7-valent vaccine was used as a placebo.
    2) Among those who received the vaccine subcutaneously, fewer than 8% used antipyretics after vaccination. Among those who received the vaccine intramuscularly, antipyretics were used by 80%.
    Loss of appetite was observed in fewer than 19% in the subcutaneous group, and in more than 54% in the intramuscular group.
    Irritability: less than 37% in the subcutaneous group, and more than 88% in the intramuscular group.
    Drowsiness: fewer than 41% in the subcutaneous group, and more than 70% in the intramuscular group.
    Sleep disturbance: fewer than 24% in the subcutaneous group, and more than 45% in the intramuscular group.
    However, the manufacturer recommends that this vaccine be administered intramuscularly.
    3) Adverse reactions that were reported spontaneously were reported in 83%-92%.
    4) In one study, serious adverse events were observed in 11.4% of children. Most of them had infections requiring hospitalization. All of them were rated as unrelated to the vaccine. The vast majority of serious adverse reactions were among infants.
    5) In total, in the group receiving the 13-valent vaccine, 35 serious complications were recorded in 25 children (out of 780). That is, the total percentage of serious complications in two studies was 3.2%. The percentage of complications from pneumococcus itself is much lower.

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Hepatitis B
Whooping cough
Haemophilus influenzae
Hepatitis A
Vitamin K
Allergies and autoimmunity
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