Adult Immunization in Diabetes - Current Recommendations

Introduction

Demographic transition of population has modified the prevalence of many diseases (1). This is a global phenomenon with reflections in India as well. Increasing life span has led to the rise in the number of elderly and also in the prevalence of Diabetes in adults. Mostly these are the people with Diabetes Mellitus Type2 which can be equated with a state of diminished immunity (2).

As the age grows, it is further compounded with comorbid conditions like Obesity, hypertension, ischemic heart diseases, Heart failure Chronic Obstructive Airway Diseases, Chronic Kidney Diseases, Chronic Liver Diseases etc. thereby increasing morbidity and mortality (2). Additionally these people have higher incidence of infections (bacterial as well as viral). Repeated use of antimicrobials leads to emergence of resistant strains, side effects of medication &longer stays in hospitals adding to cost as multiple problems make management more difficult (2).

Mortality from various infections due to emerging drug resistance and mutations in bugs continues to rise (2). This is despite use of broad spectrum antibiotics, and other support systems in intensive care units. There comes the role of preventions in which Immunization/Vaccination are of prime importance (2).

Immunization is a means of providing specific protection against damaging pathogens. Specific immunity can be acquired naturally or artificially by either passive or active immunization. Vaccines greatly reduce the risk of infection by working with the body’s natural defenses to safely develop immunity to disease. Vaccination there by becomes a novel approach to boost immunity.

Passive immunity

Natural passive immunity is acquired without challenging the immune system with an antigen. It involves transfer of serum or gamma globulins from an immune donor to a non-immune individual. Naturally acquired passive immunity is transferred from mother to fetus through placental transfer of IgG or colostral IgA.

Artificially acquired passive immunity is by transfusing with immune globulins or gamma globulins, used in many acute infection situations like diphtheria, tetanus, measles, rabies and poisoning with insects, reptiles, botulism and as a prophylactic measure in hypo gamma globulinemia².

Active immunity

Active immunity is produced by the body following exposure to antigens:

Naturally acquired active immunity is produced after exposure to a pathogen leading to subclinical or clinical infection and results in a protective immune response against exposure to the pathogens.

Artificially acquired active immunity is transferred via administration of vaccines containing live or dead pathogens or their antigenic components².

Based upon the observation that,the diabetics have lowered immunity and  are more prone to infections; the role of vaccines in them for the vaccine preventable diseases is paramount. The advancing age reduces the body response to vaccination because of immunosenescence, a term coined by Roy Walford in 1969.

The American Diabetes Association, Advisory Committee on Immunization Practices, Centre for Disease Control and Prevention, World Health Organization, United Kingdom Guidelines, Geriatric Society of India & Association of  Physicians of India have given their recommendations for the use of vaccines in type II diabetes. These recommendations are for Hepatitis B, Influenza, Pneumococcal, Tetanus, Diphtheria, Pertussis & Zoster vaccines².

They however say that people suffering from Diabetes may also be given Hib,Hepatitis A, Human Papilloma virus, Measles, Mumps, Rubella, Meningococcal, Typhoid, Varicella and Yellow fever vaccines under certain special circumstances².

Discussion will be on Hepatitis B, Influenza, Pneumococcal, Tetanus, Diphtheria, Pertussis, Hepatitis A, Meningococcal, Typhoid, Zoster vaccines, & Yellow Fever Vaccine.

Hepatitis B Vaccine (2)

Hepatitis B vaccine (HBV) is given to all unvaccinated people suffering from type II diabetes. The case for vaccination becomes stronger in them if they have additionally a history of intravenous (IV) drug use, a household contacts of persons with chronic HBV infection, occupational exposure to HBV, HIV seropositivity, chronic liver disease, chronic kidney disease, use of blood products or multiple blood transfusions or sexual exposure with patients having sexually transmitted disease (STD). it is also indicated in medico social workers &partners having HBs Agpositive. Besides full course of vaccination as post exposure prophylaxis: single IM dose of Hepatitis B immunoglobulin (HBIG)0.06 mL/kg is also given.

Influenza Vaccine

Influenza vaccine, first available in the 1940s, now two formulations per year:

One for each hemisphere (Northern & Southern) are made available. World Health Organization recommends the viral composition of each formulation, basedon the predominant circulating viral strainsgrown in embryonated chicken eggs.

There are two types of vaccines:

killed and live attenuated vaccine.

The “trivalent inactivated influenza vaccine (TIV) and the live attenuated influenza vaccine (LAIV)”, are good and are recommended for use by the advisory committee on immune practice (ACIP) for prevention of influenza.

The seasonal influenza vaccine (LAIV) is a trivalent vaccine containing two influenzas A strains:

One H1N1 type, one H3N2 strains and one influenza type b strain (each 15mg) decided by World Health Organization on the epidemiologic and antigenic analysis of the currently circulating strains².

The annual influenza vaccination (laiv) is advised to cover any mutation, which the circulating virus undergoes over the time scale. Seasonal influenza vaccine is prepared annually to include the most likely strain for the season. Over 100 countries in the world use influenza vaccines.

If an antigenic shift in the virus takes place, pandemic results. There is no pandemic virus vaccine available.

Post vaccination, antibodies develop in about two weeks’ time, which protects against influenza virus infection.

India being in the northern hemisphere the vaccination should be done by October, if possible. Vaccination should continue as long as influenza viruses are circulating. As a matter of fact, India today has two peaks of influenza, although the virus is circulating all the 12 months of the year, 365 days of the year; the vaccine could be given any time if available.

Annual vaccination against influenza is recommended for all adult diabetics who want to reduce the risk of becoming ill with influenza. Vaccination is also recommended in diabetic women who will be pregnant during the influenza season. More strong recommendations are for diabetics who additionally suffer from chronic pulmonary conditions (including Asthma), Cardiovascular diseases (except hypertension), chronic liver diseases, chronic kidney diseases, hematological diseases, metabolic disorders, persons who are on immune suppression, residents of nursing homes, chronic care facilities workers & contacts of caregivers with co-morbid medical conditions.

Schedule of vaccination²

Tiv is given only once as a single dose to elderly persons. It is available as 0.5ml liquid in prefilled syringe. This is given as intramuscular injection in the deltoid muscle or as intranasal. Yearly flu vaccination should begin in September, or as soon as vaccine is available.

Revaccination:

influenza vaccine is recommended to be administered annually.

Pneumococcal Vaccines

There are two types of vaccines namely pneumococcal polysaccharide vaccine (PPSV23) and pneumococcal conjugate vaccine (PCV13).

PPSV 23, a tetravalent pneumococcal polysaccharide vaccine was introduced in 1945. It was derived from a capsular polysaccharide of killed Streptococcus pneumoniae. The polysaccharide antigen was capable of inducing type-specific antibodies that enhanced opsonization, phagocytosis and killing of pneumococci by phagocytic cells².

In 1983 it gave way for the production of a 23-valent formulation of a polysaccharide pneumococcal vaccine (PPSV23) containing long chains of polysaccharide molecules that make up the surface capsule of 23 types of pneumococci, which include 1, 2, 3, 4, 5, 6b, 7f, 8, 9v, 10a, 11a, 12f, 14, 15b, 17f, 18c, 19f, 19a, 20, 22f, 23f and 33f serotypes. It is beneficial in Invasive Pneumococcal Disease.

PCV13, A new pneumococcal conjugate vaccine (PCV7) was introduced in 2000. Vaccine has caused significant reduction in the rates of pneumococcal disease in USA. Later PCV7 has been modified with addition of more serotypes.

During 2010 it was modified into a triskavalent vaccine containing capsular polysaccharides from 13 serotypes of pneumococcus (1, 3, 4, 5, 6a, 6b, 7f, 9v, 14, 18c, 19a, 19f and 23f) where bacterial polysaccharides are covalently conjugated to an immunogenic carrier protein containing nontoxic variety of diphtheria toxin (Prevnar 13, PCV13). The conjugate vaccine acts by binding to polysaccharide-specific b cells that communicate carrier protein antigen CRM197 to t-cells. There is t-cell dependent immune response by release of cytokines that facilitate b cells to transform into plasma cells, which in turn release antibodies.

PCV 13 has been approved by US-FDA in 2011 for use in adults 50 years of age or older to prevent pneumonia and invasive disease by Streptococcus pneumoniae.

Schedule of vaccination (3)

PPSV 23 is given only once as a single dose to elderly persons. One dose of (0.5 ml) of the vaccine contains 25 micrograms of each capsular polysaccharide antigen dissolved in isotonic saline solution with 0.25% phenol as a preservative. Revaccinationis after 5 years have elapsed since getting the first dose of pneumococcal vaccine.

PCV13 is administered in a dose of 0.5 ml intramuscularly. The preferred site is the deltoid muscle of the upper arm.

Both the vaccines are indicated in Type 2 diabetes besides  all adults above the age of50 years and in some other conditions as described below: – Persons with certain underlying medical conditions such as coronary artery disease, congestive heart failure, cardiomyopathy, chronic obstructive  pulmonary disease, cirrhosis of liver, and chronic renal failure – Immuno-compromised persons who are at high risk for   Pneumococcal infections, such as immunoglobin deficiency, human immunodeficiency virus (HIV) infection, leukemia, lymphoma, multiple myeloma, Hodgkin’s disease, non-Hodgkin’s lymphoma, disseminated malignancy–Persons receiving long term therapy with corticosteroids,  and immunosuppressive agents– Persons who have undergone splenectomy, or exhibit  anatomic asplenia, or sickle cell disease as they exhibit reduced clearance of encapsulated bacteria from the blood  stream. –Chronic smokers– Persons suffering from sleep disorders– Persons who are prone to nocturnal aspirations.

Tdap

Tdap is indicated in all type2 diabetics who have not received Tdap in childhood or are in contact with Infants, Health care personnel, during pertussis and in pregnant women. It is given in a dose of 0.5 mL intramuscular (IM) deltoid with booster dose once every 10 years^3,4.

Zoster Vaccine

Zoster Vaccine is advised to diabetics aged 60 years and older regardless of whether they report a previous episode of herpes, as a single 0.65 mL dose SC in the deltoid region. It is contraindicated if there is a history of immediate hypersensitivity reaction to Gelatin or Neomycin³.

Hepatitis A Vaccine

Hepatitis A Vaccine is indicated in all type 2 diabetics specially if they are at high risks like Illicit drug use, suffering from Hemophilia, infected with other hepatitis viruses, having CLD and not immune to hepatitis A virus (HAV), received or awaiting liver transplant or are Food handlers & MSM³.

Measles, Mumps and Rubella (MMR)

MMR vaccine is indicated in all Type2 diabetics except those having suffered from all the three disease or have received 2 doses of measles, mumps and rubella (MMR) vaccine in the childhood or are health care workers. 

Meningitis Vaccine

Meningitis Vaccine is advised to all Type 2 diabetic during meningococcal outbreaks and if they are visiting fairs/mass religious congregations 10-14 days prior to their visits³.

Typhoid vaccine

Typhoid vaccine is recommended as part of routine immunization in type 2 diabetics like other adolescents or for travellers to areas where there is a moderate to high risk of exposure to Salmonella typhi. Either Ty21a or Vi vaccine may be used as both have comparable efficacy (51%vs 55% at 3 years) and both are safe(3).

Yellow Fever Vaccine

Yellow Fever Vaccine is advised to diabetics like any other person if they are travelling to endemic zones of yellow fever³.

Drawbacks

There are drawbacks in the path of proper immunization. They are due to apathy on the part of clinicians, diabetics taking immunization lightly, cost factors, non-reimbursement of vaccines, complicated regimens etc. This is also a fact that all strains are not covered in the vaccine. Increasing immunosenescence with advancing age leads to poor response to vaccines which forms an argument against vaccination.

Conclusion

Vaccination in children have yielded positive results and on the same logic vaccinations in adults are also indicated. Diabetes a condition being equated to diminished immunity leads to higher incidence of both bacterial as well as viral infections, deserve protection from all vaccine preventable diseases by appropriate vaccines. All strains in vaccines are not covered but still the protection offered is good enough to be lifesaving. Due to immunosenesence the booster doses are required. An awareness on prevention needs to be made in medical community as well as in masses (3). The number of diabetics is increasing and so is increasing Co morbid conditions. Infections Drugs uses, Hospitalization are a putting Dent on economy. In a situation like this Preventive Vaccinations will play a vital role.