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Вакцинация в современном мире
E. David G. McIntosh AM1, L.S. Namazova-Baranova2, 3, 4
1 Imperial College, London
2 Scientific Center of Children's Health, Russian Academy of Medical Science, Moscow, Russian Federation
3 N.I. Pirogov Russian National Research Medical University, Moscow, Russian Federation
4 I.M. Sechenov First Moscow State Medical University, Russian Federation
Infectious diseases and their prevention across the Seven Ages of Man
Контактная информация:
E. David G. McIntosh, Honorary Clinical Senior Lecturer, Imperial College, London, Honorary Professor, Scientific Center for Children's Health,
Russian Academy of Medical Science Email: [email protected]
Статья поступила: 23.10.2012 г., принята к печати: 02.11.2012 г.
This paper will describe some important infectious diseases and their prevention, to illustrate the interconnectedness of people at different ages. The diseases of interest are congenital infections, bacterial meningitis, rotavirus and human papillomavirus, healthcare associated infections, and influenza. Vaccination of individuals in one age group, for example children, may confer benefits on adults and vice versa. Of particular interest is vaccination of the pregnant woman, especially with regards to pertussis and influenza.
Key words: infectious disease, prevention of bacterial meningitis, rotavirus, human papilloma virus, nosocomial infections, influenza, whooping cough, children.
(Педиатрическая фармакология. 2012; 9 (6): 6-8)
INTRODUCTION
This could be described as a «circular» paper. It describes important infections and their prevention in seven ages of men (and women): fetus, infant, child, adolescent, young adult, older adult, elderly. By including pregnant women, the focus returns to the fetus. The interconnections will be highlighted: infections can affect more than one age group. Prevention of infection in one age group has the potential to protect other age groups as well. This is known as herd protection and is an important added benefit from vaccination.
CONGENITAL INFECTIONS
The observation that women suffering from rubella during their pregnancy are at risk of having babies with congenital abnormalities such as eye and ear defects, was made by the Australian ophthalmologist Norman Gregg in 1941 [1] and published in the Transactions of the Ophthalmological Society of Australia [2]. Surprisingly, despite the availability of excellent vaccines against rubella [3], the disease is still prevalent and efforts at elimination are still ongoing [4].
Other congenital viral infections are also preventable with vaccination: herpes zoster and hepatitis B virus for example. Vaccination against these infections is offered ideally before pregnancy. The effects of influenza during pregnancy were described nearly 100 years ago [5] and this problem came to the fore recently during the influenza A (H1N1) pandemic of 2009 [6]. Now, in a number of countries, seasona l influenza vaccination is offered during pregnancy [7].
Regarding congenital bacterial infections, neonatal tetanus remains an important cause of neonatal death globally — maternal tetanus vaccination (with DTP, DT, TT or Td) prevents this [8]. Maternal infection with Streptococcus agalactiae (group B streptococcus) also has the potential to cause neonatal infection (both early-onset and late-onset) — currently, prevention is by means of intra-partum
antibiotics [9, 10]. However, in the future, it is expected that maternal vaccination with group B streptococcus vaccine will afford the protection currently granted by antibiotics [11, 12].
INFECTIONS OF THE INFANT AND CHILD
Of all the feared infections of infancy and childhood, bacterial meningitis counts as one of the most feared. Three organisms are responsible for the majority of these infections: Haemophilus influenzae type b (Hib), Streptococcus pneumoniae and Neisseria meningitidis. The ability of a plain polysaccharide Hib vaccine to prevent Hib infection in older children was demonstrated in a large randomised study performed in Finland and reported in 1977 [13]. Unfortunately, this plain polysaccharide vaccine was poorly immunogenic and poorly protective in those under 18 months of age. It was not until the advent of Hib conjugate vaccines that the true potential of these vaccines was realised [14].
Invasive pneumococcal disease (IPD) has various clinical manifestations such as meningitis, septicaemia, pneumonia and otitis media. Again, it was not until the widespread deployment of pneumococcal conjugate vaccine (PCV) that the full benefits could be reported [15]. The original 7-valent PCV is being replaced by 10-nd 13-valent versions, and the further benefits of PCV are now starting to be enjoyed [16].
Invasive meningococcal disease (IMD) not only has two major acute clinical manifestations, meningitis and septicaemia, but also it has other acute manifestations which make it difficult to detect and diagnose [17]. Those who survive the initial infection also have a risk of suffering from longer-term poor physical and cognitive outcomes [18]. Pace and Pollard [19] conclude: «The only rational approach to the prevention of meningococcal disease and the associated suffering is through vaccination».
Indeed, vaccines against meningococcal serogroups A, B, C, W-135 and Y have been deployed in various parts of the World [20]. Nadel [21] concludes: «Everything that can be
done to reduce the consequences of meningococcal disease, including improvements in recognition and management, improvements in diagnostics, and most importantly, prevention of disease, is essential to improving the life chances of children and their families». Unfortunately, the serogroup B vaccines to date have only targeted specific (geographic) strains; serogroup B vaccines with broader coverage are expected to have broader geographic applicability [22].
The added benefit of herd protection has been observed with Hib vaccines [23, 24], with PCV vaccines against IPD [25] and with serogroup C meningococcal conjugate vaccines [26]. One author goes as far as to say that: «Herd immunity accounts for around 50% of the protection by serogroup C meningococcal conjugates, 7-valent pneumococcal conjugate vaccine and H. influenzae type b conjugates» [27].
In Australia, there is a suggestion of herd protection arising from the national rotavirus immunisation programme [28]. By contrast, in Singapore, it has been shown that relying on herd protection is inadequate with regards to rubella vaccination — very high levels of vaccination are required, along with identification and vaccination of susceptible women, in order for individual members of the population at large to be protected against rubella [29].
ADOLESCENT AND YOUNG ADULT
Whilst adolescents and young adults are at extremely low risk for Hib disease and IPD, they are susceptible to invasive meningococcal disease through a number of social and behavioural risk factors [30]. These risk factors are different from those applying to infants and young children. But in a similar observation to that of Viner et al. [18] in which infant and young child survivors of IMD are at risk of poor long-term outcomes, Borg et al. [31] also conclude: «Survivors of invasive meningococcal disease in adolescence have a disturbing series of deficits, including poorer physical and mental health, quality of life, and educational achievement». Protection with meningococcal vaccines is as important to adolescents and young adults as it is to infants and young children.
An area where herd protection is being observed in the adolescent and young adult population is that of human papillomavirus (HPV) vaccination [32]. This study reported that: «The decrease in vaccine-type HPV not only occurred among vaccinated (31.8% vs 9.9%, p < 0.001) but also among unvaccinated (30.2% vs 15.4%, p < 0.0001) postsurveillance study participants». Moreover, this observation occurred within 4 years of the licensing of the quadrivalent HPV vaccine.
Herd protection can work in unusual ways — due to waning pertussis immunity, adults become at risk for pertussis and in fact contract the infection [33]. This is a particular problem in pregnant women and their newborn infants — but by vaccinating the pregnant woman, it appears that enough antibody can be transmitted to the newborn infant to protect it until the time he/she is due for vaccination [34].
OLDER ADULTS
This age group is likely to have members who require hospitalisation for surgery, transplantation, cancer treatment, intensive care and for conditions associated with chronic illness. They are therefore at risk of healthcare associated infections. Acinetobacter baumannii is an example of a healthcare associated infection, one that is particularly difficult to treat and one that is associated with a high degree of morbidity and mortality. Whilst antibiotics are the mainstay of the management of patients infected with this organism, there are Acinetobacter baumannii vaccines
under development which may provide an extra barrier of protection for those at risk [35].
An infection which is more prevalent and more ubiquitous is that due to Staphylococcus aureus. Whilst the infection can affect all age groups, those in hospital are at particular risk. But because of the wide variety of antigenic targets, the search for a suitable vaccine target or targets is elusive [36]. Vaccine development has been difficult, although some to hold promise, for example in preventing staphylococcal pneumonia in the animal model [37].
THE ELDERLY
Exposure to antibiotics and hospitalisation are the major risk factors for Clostridium difficile infection, and the elderly are particularly susceptible to this form of diarrhoea [38]. Whilst there are emerging new strains such as a fluoroquinolone-resistant, binary toxin-producing B1/NAP1/027, vaccines have been developed which are themselves toxin-based, for example enterotoxin TcdA and cytotoxin TcdB. DNA vaccines which target the receptor-binding domain of Clostridium difficile toxin A have also shown promise in animal models [39].
Influenza also becomes an increasing problem with increasing age. The pandemic influenza A (H1N1) was associated with high morbidity, hospitalization and mortality in Russia [40]. But the greatest burden was carried by those less than 15 years of age [41]. What does this mean for the elderly? We know that elderly person enjoyed protection from influenza in Japan in the 1970s and 1980s by virtue of the fact that schoolchildren were being vaccinated [42]. We also know the «excess» deaths in the elderly increased (presumably due to influenza) when this schoolchildren influenza vaccination programme was ceased in 1994 [43]. There is evidence that vaccinating children with influenza vaccine can also protect adults, including the elderly, by means of herd protection [44].
Finally, and to come full circle, influenza vaccination in pregnancy was established as early as the 1950s and 1960s [45]. There were no deleterious effects on infants over a 7-year follow-up. There is even a suggestion that maternal influenza immunization may reduce the risk of preterm and small-for-gestational-age babies [46].
CONCLUSIONS
There are connections between infectious diseases in the Seven Ages of Man. Vaccination of infants and children against pneumococcal infection and influenza may afford a degree of protection to unvaccinated adults and the elderly. Vaccination of adults, including pregnant women, against pertussis may prevent inadvertent pertussis infection in infants too young themselves to be vaccinated. Vaccination of pregnant women against influenza is now recognised as part of routine standard of care.
Vaccination against conditions such as rubella and meningococcal infection are of such absolute importance that it is just as important to maintain high levels of vaccination as it is to rely upon herd protection.
Vaccination against healthcare associated infections in the future may confer benefits on other patients in particular and on the healthcare system in general. In the future, vaccination of pregnant women against group B streptococcus has the potential not only to protect the newborn but also to reduce antibiotic consumption.
DECLARATION OF INTEREST
EDGM is the Global Scientific Affairs Senior Expert for Novartis Vaccines, manufacturer of Hib, meningococcal and influenza vaccines.
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Вакцинация в современном мире
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