In this session, we will focus on age and its effects on disease transmission and severity. In the previous session, we mentioned that age is the most important attribute of a host from the perspective of infectious diseases. The figure on the slide shows one reason for this: infection with a particular disease can be more or less severe depending on the age at which a person is infected. For many infections, the case-fatality ratio, or risk of dying if infected, is greatest for people infected at young age, as shown in this figure. Note that the axes are logarithmic, so each gradation is 10 times more fatal than the one below. For these diseases, protecting infants from infection is a particularly high priority, and fortunately we have excellent vaccines for each of them, though the resurgence of pertussis in some parts of the world is an area for concern. Some other infections are particularly dangerous when contracted at older ages. Chickenpox, or varicella virus infection, is only rarely fatal but it is more likely to fatal in adults and older adolescents as well as in infants. In the case of rubella, infection is rarely severe for the infected person, no matter what their age. but we are concerned about rubella because if a pregnant mother is infected it can cause severe health consequences for the fetus she is carrying. Therefore, a goal of public health policy is to prevent rubella cases in women of childbearing age, while prevention in males and in females of other ages is a lower priority. Host age also affects both the likelihood of becoming infected and the likelihood of passing on infection to others. Mainly, this is because people of different ages have different numbers and different types of contacts each day, and these contacts each have some probability of leading to the transmission of disease. These graphs show the numbers of contacts per day between people of different ages in four European countries, with blue being low and white being high. You can see that the largest numbers of contacts in white are among persons under 20 or so and that most of these contacts are with people of about the same age. Contacts between individuals of the same age are shown on the diagonal. You can also see what look like green wings on the graph which show contacts between people of parenting age and children. Prior to this study, called the POLYMOD study, epidemiologists had inferred from incidence rates in different age groups, that contacts were more frequent among children than adults and that they were assortative, meaning that individuals preferentially contact those of a similar age. POLYMOD confirmed this based on survey data and gave numbers to the specific mixing patterns. while also allowing comparisons across countries. These contact rates affect both an individual’s likelihood of getting infected and an individual‘s ability to pass on infection once they become infected. When one group in a population is both more likely to get infected and more likely to pass infection on, that group is sometimes called a core group for transmission of the disease involved. Core groups are even more likely to form, if contacts are assortative, meaning that most contacts that transmit disease transmit within the core group rather than spilling out into other groups. While epidemiologists differ in their precise definition of a core group, the fundamental idea is that it is the group of persons in the population who sustain transmission while other groups most often become infected through a chain of transmission that can be traced back to the core group. For example, in infections transmitted mostly by close contact or by respiratory contact, children are often a core group, because they contact one another frequently and transmit the infection among themselves, but they also contact adults in some cases infecting those adults. This notion is useful in thinking about control measures, as it may be possible to reduce the burden of disease considerably in the population as a whole just by vaccinating the core group. Starting in 2000, the pneumococcal conjugate vaccine, called PCV7, was given to infants and toddlers in the United States. This graph shows the decline in invasive disease from the types of pneumococcus included in the vaccine in the years following introduction by age group. At left is the age group that actually received the vaccine, which had the largest burden of disease and also showed the biggest reduction with vaccine introduction. But disease declined in all other age groups too because the youngest children in the population were a core group for transmission and the infection spilled out from that group. Epidemiologists partitioned the averted cases - cases that didn’t happen because of infant and toddler vaccination - into those that could be attributed to direct protection in the vaccine recipients and those that were in unvaccinated people who were protected indirectly by herd immunity. About 2/3 of the averted cases were attributed to herd immunity, even though only a small fraction of the population about five years worth of birth cohorts, had been vaccinated. When a particular age group is both very important in transmitting an infection and also at high risk of severe consequences when infected, it clearly makes sense to vaccinate that group. In the case of pneumococcal disease, infants and toddlers are one of the two age groups, along with the elderly, that get severe disease and they are also key to transmission so they were a natural choice for vaccination. In other cases, the core age groups that maintain transmission may not be those at greatest risk of severe consequences. For example, influenza infection in children over two is rarely life-threatening but it poses a high risk to the elderly adults or people with other predisposing conditions, such as certain heart and neurological conditions. In this case, there are two different approaches to protecting the persons at high risk. The first is to vaccinate the members of the high-risk group. The second is to vaccinate a large fraction of the core group in an effort to reduce transmission and protect the high-risk group indirectly. A randomized controlled trial of influenza vaccination in Canada estimated that vaccinating children against flu could reduce the incidence of flu in adults by 39 percent, even though the adults themselves did not receive flu vaccine. An additional complication is that elderly people, the ones that would benefit most from immunity to flu, don’t make a very strong immune response to the vaccine, so vaccinating them may not give them full protection. For this reason, a combined strategy of using influenza vaccine for high risk groups and also for children who are key to transmission is increasingly popular. In practice, this means recommending flu vaccination to everyone.