3Immunization in Adults: Introduction and General ConsiderationsChapter 1

Three “emerging infectious diseases” of the last two decades necessitated adult immunization in India. In 2006, India introduced Japanese encephalitis (JE) vaccine into UIP primarily to address large scale outbreaks in Eastern Uttar Pradesh, Assam, and selected districts in a few more States. It was then extended to adults in 2011 onward in Assam since adult JE was found to be common.

In 2009, a pandemic caused by influenza virus A H1N1-pdm09 started in North America and reached India. When H1N1 vaccine became available, it was widely used in health care in India particularly in adults over 60 years. Currently, annual immunization with quadrivalent influenza vaccine (recommended strains of A H1N1; A H3N2; B Victoria; B Yamagata) is regularly offered in many hospitals to senior citizens. It is also to be recommended in pregnant women as it prevents severe disease in them and their infants.

The pandemic of Coronavirus disease of 2019 (COVID-19) broke out in early 2020. In unprecedented speed, vaccines became available by the last quarter of 2020 and the first quarter of 2021. On 3 January 2021, Government of India gave emergency use authorization for adult immunization with either of two vaccines—Covishield and Covaxin.

These three vignettes illustrate that adults also deserve immunization as their risks for disease become recognized and vaccines are available.

The first immunity gap is due to escaping infection as child, and growing up without immunity. JE in Assam illustrated this. Only first infection carries the risk of disease. Once infected, robust immunity develops and consequent protection is lifelong. The natural 4history of polio is similar in that only the very first infection with types 1, 2, or 3 carries the risk of polio paralysis. Since wild polioviruses are highly contagious, no child could escape infection, and all adults were protected. Since JE is mosquito-transmitted, its epidemiology is restricted by the bionomics of vector mosquitos and variations in age distribution can occur.

Hepatitis A infects many, if not most children, but some do escape. One infection provides lifelong immunity. Those who escaped infection in childhood may get infected at any age: Adult hepatitis A can be severe, even leading to liver failure. Those with any chronic liver disease are particularly vulnerable.

Varicella in India occurs in adults in many communities. Consequently, outbreaks in hospital workers are fairly common and it is a wise policy to check during recruitment the past history of chickenpox. Chickenpox in hospital staff is a risk for infection in immune-compromised patients who may have serious consequences, even fatality. Anyone without past experience of chickenpox deserves varicella vaccination, irrespective of age or occupation.

Hepatitis B infection is most often silent; hence history of past illness is no help to distinguish immune from nonimmune. A practical policy is to vaccinate all freshly joining staff and students in medical and nursing establishments. Others also deserve protection.

A second reason for immunity gaps in adults, against endemic diseases, is related to the pathogen changing its antigen profile, which we call “antigenic drift.” Endemic/seasonal influenza A H1N1 and H3N2 develop antigenic drift during prolonged circulation; hence, appropriate strains are chosen by the global influenza control program of the World Health Organization (WHO) for annual vaccination, separately in Southern Hemisphere and Northern Hemisphere. Another peculiarity of influenza immunity is that high levels of humoral immunity are necessary for protection, because spill-over antibodies on nasal and pharyngeal mucosal surfaces are needed for protection from disease. Although infection itself will boost antibody by memory recall, it will take a few days to kick in, whereas the incubation period of influenza is 1 or 2 days—hence reliance on immunological memory alone is insufficient. Adequate level of spill-over antibodies must be ensured prior to exposure for protection, for which purpose high levels of humoral immunity must be maintained always. That is the rationale of annual influenza vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is similarly highly prone to antigenic drift on account of the emergence of variants of concern. They have the tendency for evasion, or even outright escape, from immunity. Therefore, bolstering immunity levels by way of boosters are necessary—the higher the immunity achieved, the broader its protective effects, as is obvious from vaccine effectiveness observations. Some countries have begun giving second boosters for this reason. What does the future hold? I had predicted, way back in March 2020, that SARS-CoV-2 will become universally endemic, or pan-endemic. Policies of immunization during endemic infection have to be made, but periodic boosters may be one option that must be considered.

The third reason for immunity gap is immune-senescence due to ageing. All adults are not equal, immunologically. It was in 1999 that Indian Academy of Pediatrics adopted the policy that its purview covered all children and adolescents up to and including 18 years. That brought the legal and health care 5definitions of adults close: For us, all 19 years and older are adults. Arbitrarily, we may consider all 19–39 years as young adults; 40–59 as middle-age, and all 60 years and above as senior citizens—sexagenarians (60–69), septuagenarians (70–79), octogenarians (80–89), nonagenarians (90–99), centenarians (100–109), and supercentenarians (all 110 and above).

We have a predominantly young population in India—the median age is about 28 years—which means that 50% of population is below 29 years of age. Those above 80 years are <14,000,000 or about 1% of total population. Infectious diseases take a heavy toll of lives during their productive years of life and after retirement. We must ensure that no adult dies of vaccine-preventable diseases in our country.

In response to “nonself” exposure and stimuli, in our context infection, the immune system is called to respond. Defense responses are a continuum of inflammation, innate immunity, and adaptive immunity. Ageing of the inflammatory processes is called inflamm-ageing, which affects innate immunity as well; ageing of adaptive immunity is immune-senescence. The vaccinology of immune-senescence is discussed in another chapter.

While adults would have responded to many locally prevalent infectious agents and have accumulated memory cells and immune memory, immune senescence puts them at a disadvantage. Proportionally, naïve B and T-cells may now be a minority, crowded out by memory cells stimulated by a plethora of past infections. Where infectious diseases are controlled through functional public health system, life expectancy increases.

The capacity to generate new naïve cells would also decline by ageing, putting older adults at much immunological disadvantage. In short, senior citizens are vulnerable to many infections, as if the microbes were “opportunistic” under the circumstances. We should do the opposite and offer vaccine boosters to overcome the immunity gaps due to senescence as best as we can.

Moreover, many adults, middle age onward, have nutritional and metabolic (noncommunicable) diseases or their predisposing factors that may worsen the problems that the immune system has to face. Altogether adults are vulnerable, immunologically speaking, and our expertise must be put to work against those disadvantages.

The importance of individualizing immunizations, from choice of antigens/vaccines to the timing and planning schedules with the number of doses, is our responsibility. Therefore, we need to know the background frequencies of ubiquitous and locality-specific pathogens, the risks of their diseases, the availability of various vaccines, their comparative merits and precautions, in order to serve adults with competence and accountability.

In senior citizens, pneumonia may follow bacteremia without upper respiratory symptoms. Fever and chills give away the clue to bacteremia. Often these are the only symptoms of early pneumonia and physicians are prone to miss the signal. By the time cough and sputum appear, the person would have slipped into multiorgan failure with fatal outcome. All these can be prevented by vaccinating senior citizens. My personal recommendation is for Prevnar 13 followed after 6 months with 23-valent nonconjugated vaccine, once during life.

Varicella virus is well known to set up latent infection in posterior nerve root ganglia. As immunity wanes, the probability of “reactivation” disease—herpes zoster—increases. However, we do not see herpes zoster as often as western country physicians see in their countries. One reason may be that chickenpox in India has an age shift upward and the risk of zoster is partly determined by duration of latent infection. Most persons with past chickenpox may not have lived long enough for high risk of zoster. Our life expectancy at birth is lower than in western countries, and senior citizens (above 60) constitute only 10% of our population, while it is over 20–25% elsewhere. Two zoster vaccines are licensed for use in few countries.

Once we understand all such issues, we are justified in using the word immunization for vaccination. So, purposeful vaccination, with good justification, and adequate confidence supported by actual documentation of desired immune response(s), or in its absence by evidence in the medical literature, qualifies for immunization.

Any or all detected immune response(s), and the idea of “immunity” as protection, need not be fully aligned. Immune response(s) that are “protective” against a given disease is the true value of immunity. Technically speaking, the presence of any immune response as detected against selected antigens is also immunity. It may be antibody- or cell-mediated response. Protection in this context, or immunity in the practical sense, has a range of functions. At one end of its spectrum is protection from severe disease threatening fatal outcome—which is the minimum we desire by immunization. At the other extreme end of the spectrum is protection from infection itself. The gradient of benefit lies in between.

The term “sterile immunity” has been used when immunity prevents even the very first event of pathogen entry into a sterile or “prohibited” site in the body, or, the entry of a virus inside a host cell that 7initiates infection. Immunization with human papillomavirus (HPV) vaccine does just that—once immunized, the particular HPV genotype is not allowed cell entry. If even one cervical epithelial cell is infected, the spread to contiguous cells cannot be prevented by immunity. Unlike other viruses, HPV spreads from cell to cell without giving a chance for virus neutralizing antibodies to stop further spread in the intercellular spaces. Vaccine-induced immunity is high enough for spill-over antibodies on the cervix all the time, protecting from infection per se, consequently protection from cancer induced by the genotypes in the vaccine.

Earlier we saw that this principle of sterile immunity is what we aim for, through annual influenza immunization. We need protection from influenza viruses causing infection, for which high levels of humoral immunity must be maintained. Even if “breakthrough” infection occurs, the diseases is rendered mild due to antibodies in body fluids—particularly in intercellular spaces.

Since there is no highly effective vaccine to protect from malaria, antimalarial drugs are recommended when traveling to malaria-prone areas.

When travelling to a country in which yellow fever is prevalent, immunization is important, and even required by international travel regulations and visa approval. For those who travel from places without enzootic and endemic JE to JE-affected countries, pretravel immunization is a good precaution.

In this manner, there is a discipline called “Travel Medicine” and experts will have up-to-date information of the geographic prevalence and risks of various infectious diseases and the availability of various vaccines.

Eating out is either fashion or necessity these days—and food-borne infectious diseases are notorious in this context. All food-handlers—in road-side eateries to five-star hotels and everything in between—ought to be vaccinated against certain food-related infectious diseases and their microbial infections. Typhoid and hepatitis A immunizations are particularly relevant for both groups of people on either side of the food counter–those who cater and those who consume. International travelers going to countries where either or both are endemic should be up-to-date with their immunization.

Healthcare is the “felt need” of everyone who feels ill. The healthcare system is approached by the individual for diagnosis and treatment. The physician can/must take an extra step and consider immunization as “preventive medicine.”

The idea of “family practice” or “general practice” is for long-term care of members of families, or individuals, who ought to return to the same clinic repeatedly and not change clinics such as “shopping around.” In family and general practice, medical records should 8be maintained long term and the physician should give timely advice for immunization when relevant, on the basis of the several criteria described in this and other chapters in this book.

In healthcare, various specialty departments will immunize those who come under their care—obstetricians will immunize pregnant women; transplant experts will immunize transplant recipients according to protocol; oncologists will do likewise for those with malignancies on therapy.

Public health is the “art and science of disease prevention and health promotion” among citizens. Adult immunization in clinical practice is not a substitute for the government using immunization as a tool for prevention of diseases in the citizens. Unfortunately, India does not have a public health division in the government and for that reason no platform to make and implement policies on adult immunization.

When our government establishes a public health division, hopefully earlier than later, the entire gamut of health promotion and disease prevention can be systematized and reduction of disease frequencies monitored through reliable counting processes. This is known as “public health disease surveillance.” Once public health division is functional, UIP can be subsumed in it and the purview of immunization expanded to adults.

When immunization is brought under public health, the fall in disease burden may be higher than what may be accounted for by immunization coverage alone. This phenomenon is called “herd effect” while actual coverage achieves “herd immunity.” In simplified language, the proportion with immunity is herd immunity—infection-induced and immunization-induced immunity. The fall in disease incidence among the unimmunized on account of high herd immunity achieved through immunization is herd effect. The importance of these issues is related to “socio-economic development” of the nation.

When immunization is utilized maximally, healthcare centers will be uncluttered of vaccine-preventable diseases. Families will not need to spend money for treatment of vaccine-preventable diseases. Employed persons will not lose working days to diseases, and national productivity will increase. Professional practice of adult immunization added on the UIP platform is our contribution to nation building.