|Year : 2017 | Volume
| Issue : 3 | Page : 160-168
A practical guide to adult vaccination for patients with autoimmune inflammatory rheumatic diseases in India
Sharath Kumar1, Prasandeep Rath2, Anand Narayan Malaviya3
1 Department of Rheumatology, Columbia Asia Hospital, Bengaluru, Karnataka, India
2 Department of Rheumatology, Max Super Speciality Hospital, New Delhi, India
3 Department of Rheumatology, ISIC Superspeciality Hospital, New Delhi, India
|Date of Web Publication||08-May-2017|
Anand Narayan Malaviya
Flat 2015, Sector B-2, Vasant Kunj, New Delhi - 110 070
Source of Support: None, Conflict of Interest: None
Autoimmune inflammatory rheumatic diseases have intrinsic increased risk of infection. The medications used in these diseases may further increase the infection risk. Therefore, vaccinations have gained increasing importance in preventing them in a most cost-effective manner. In this “practical guide,” the vaccines, their schedules, pricing, and the lifetime cost analysis, specifically for the Indian patients, are described in clear, concise language. Case scenarios have been used to further simplify the understanding of the vaccination schedules. This document can be kept in the clinic for day-to-day help in ensuring that the patients are properly covered against these preventable infections.
Keywords: Autoimmune diseases, cost analysis, immunocompromised state, India, practical guide, rheumatic diseases, vaccination
|How to cite this article:|
Kumar S, Rath P, Malaviya AN. A practical guide to adult vaccination for patients with autoimmune inflammatory rheumatic diseases in India. Indian J Rheumatol 2017;12:160-8
|How to cite this URL:|
Kumar S, Rath P, Malaviya AN. A practical guide to adult vaccination for patients with autoimmune inflammatory rheumatic diseases in India. Indian J Rheumatol [serial online] 2017 [cited 2019 May 22];12:160-8. Available from: http://www.indianjrheumatol.com/text.asp?2017/12/3/160/205757
| Introduction|| |
Autoimmune inflammatory rheumatic diseases (AIRDs) are systemic in nature with increased risk of infection. Immunomodulatory medications including glucocorticoids (GCs) and more recently biologicals that are increasingly being used to treat AIRDs may further increase susceptibility to common infections. Several updated guidelines and reviews are available for adult vaccination including those for diseases with varying degrees of immunocompromised state.,,,,,,,,,,, Most of them are detailed write-ups with crowded tables, making them incomprehensible for a harried rheumatologist. There is an additional problem pertaining to vaccination for one of the common infectious comorbidities in rheumatology, namely pneumococcal pneumonia. The pneumococcal conjugate vaccine (PCV13) was approved for use in adults in India only in the year 2012. Thus, the majority of the patients presently under follow-up in rheumatology clinics would have only received the pneumococcal polysaccharide vaccine against 23 serotypes (PPSV23). Now, with the availability of PCV13, rheumatologists need to know when and which of the two of the available pneumococcal vaccines would be appropriate for such patients. This short communication provides evidence-based definitive recommendations for vaccination among adult patients (>18 years of age) with AIRDs that is based on the available evidence. The practical tips and case scenarios would be useful for a general rheumatologist in his/her busy practice.
| General Principles|| |
- Despite varying degrees of immunocompromised state in patients with AIRDs, the response to vaccinations is adequate in most cases. Even if the response is somewhat blunted in some situations (e.g. response to pneumococcal vaccine in patients taking low-dose methotrexate), it is still better than having some protection against no protection at all. Therefore, adult vaccinations are strongly recommended in this group of patients.
- There could be also some reservations among rheumatologists regarding the efficacy of vaccinations because of the drugs used in AIRDs. These medications are often identified as “immunosuppressive.” In this regard, the recommendations from the United Kingdom have given a definitive statement: “Long-term stable low-dose corticosteroid therapy (defined as <20 mg prednisolone per day for more than 14 days) either alone or in combination with low-dose nonbiological oral immune-modulating drugs (e.g., methotrexate ≤25 mg per week, azathioprine ≤3 mg/kg/day, or 6-mercaptopurine ≤1.5 mg/kg/day) is not considered sufficiently immunosuppressive and these patients can receive the vaccine. Specialist advice should be sought for other treatment regimens.” Therefore, patients with AIRDs must be vaccinated just like normal adults. The only exception is the use of live (attenuated) vaccines, for example, herpes zoster (HZ) vaccine. Being a live vaccine, there are certain precautions that need to be followed. This is especially true if biologicals are being considered. This point has been discussed in detail in the following text.
- Influenza and pneumococcal vaccine may be given at the same clinic visit reducing the chances of default. The only caution needed is that the vaccines are given at two separate sites.
| Influenza Vaccine (Flu Shots)|| |
There are at least six influenza vaccines available in India manufactured by different pharmaceutical companies,,,,,,,,,,,,, namely, “Fluarix” (GSK), “Nasovac” (Serum Institute of India), “Agripal” (Panacea Biotec), “Influvac” (Abbot), “Influgen” (Lupin), and “Vaxigrip” (Sanofi). With the various types of flu in India (swine flu, bird flu, and seasonal flu), which one of these should be recommended? What would be the best time of the year for administering the yearly booster dose?
Adult patients should receive yearly flu shots. In most parts of India, the best time to vaccinate is just before the onset of monsoon months (i.e. April–May; it can be given even in later months although the delay will reduce the period of “coverage” from a full year to only a few months). On the other hand, the best time to administer influenza vaccine for temperate climates in the northern regions such as Kashmir and northern hilly regions and the extreme southern areas such as Chennai and Vellore (South of Bengaluru) is ideally September–October. “Fluarix” is a quadrivalent vaccine, and in view of the concerns regarding its efficacy, the Centers for Disease Control and Prevention (CDC) recommends that this vaccine should not be used during the 2016–2017 influenza season. The same is true for “Nasovac,” a nasal spray that is delivered as a live attenuated vaccine. Since live vaccines are generally contraindicated in patients on immunosuppression, they are generally not used by rheumatologists even if indicated. Among the remaining four vaccines (all of which are trivalent vaccines) while “Influvac” (Abbot) and “Agripal” (Panacea Biotec) are inactivated subunit vaccines, “Vaxigrip” (Sanofi) and “Influgen” (Lupin) are inactivated split virus vaccines. All trivalent vaccines contain H1N1 in their composition. They also contain components of influenza strains which were active in the previous winter (data released by the World Health Organization [WHO] in February of the following year). Among them, “Influvac” and “Vaxigrip” are more easily available and have more premarketing studies to back their efficacy. Both the vaccines have nearly the same efficacy. Both “Influvac” and “Vaxigrip” have <0.05 μg/0.5 ml per dose of egg albumin, which is too small to cause any reaction. Therefore, it is not contraindicated for patients with egg allergy. Nevertheless, it should be given by a trained person within a facility with available resuscitation measures, especially in patients with a known history of severe egg allergy. It is of note that an adequate antibody response to influenza vaccine takes about 2 weeks. Therefore, as mentioned above, the vaccine should be administered before the beginning of the flu season which, in India, starts with the onset of monsoon.
| Pneumococcal Vaccination|| |
Scientific basis of pneumococcal vaccine
ThePPSV23 is the first pneumococcal vaccine derived from a capsular polysaccharide. It directly stimulates the B-cells without the involvement of T-cells (thus isotype switching does not occur), induces type-specific antibodies (mostly IgM isotype) that enhance opsonization, phagocytosis, and killing of Streptococcus pneumoniae (pneumococcal) bacteria by phagocytic immune cells. Being primarily a B-cell stimulant, its response is not very vigorous (compared to the conjugate vaccine) and the immunological memory is also not long-lasting; it wanes over time. Therefore, one or two boosters (at ≥5-year interval) are required to maintain adequate antibody levels. In contrast, the PCV13 is a tridecavalent vaccine, meaning that it contains 13 serotypes of pneumococcus (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F), which are conjugated to diphtheria carrier protein. Due to the presence of the carrier protein, it is highly immunogenic and the immunity is T-cell based with long-lasting immunological memory. Therefore, a single dose is good for a lifetime.,,,,,,,,,,,,
Clinical aspects of vaccination against pneumococcal disease
In patients <65 years of age, the vaccination schedule depends on the indication for vaccination. In normal immunocompetent adults <65 years, neither of the vaccines is recommended. However, persons with AIRDs are immunocompromised due to their disease per se additionally, some of them may be taking immunosuppressive drugs (e.g. cyclophosphamide, azathioprine, and high-dose GCs) causing further problem. Therefore, adults <65 years of age who have AIRDs (including iatrogenic immunosuppression) must be vaccinated. On the other hand, in patients ≥65-years of age, there is no significant differentiation between immunocompetent and immunocompromised adults; both the groups must be vaccinated.
Schedule for pneumococcal vaccines
- General rule of administering PPSV23 in a pneumococcal vaccine naïve adult (≥19 years of age) patient:
- If the patient is <65 years of age: a total of two doses are given at a minimum time interval of 5 years
- If the patient is >65 years of age: Only a single dose of PPSV23 can be given
- General rule of administering PCV13 in a pneumococcal vaccine naïve adult (≥19 years of age) patient: The patient is given only a single shot of the vaccine in a lifetime
- As a rule, among patients with AIRDs, PCV13 is given first followed by PPSV23 at >8-week interval. (Note: For normal immunocompetent adults, pneumococcal vaccines are not recommended at age <65 years. At age >65 years, it is recommended to vaccinate them with a single shot of PCV13 followed by a single shot of PPSV23 at least after an interval of 1 year. Note the difference in the recommended time interval between PCV13 and PPSV23 among normal immunocompetent adults and the patients with AIRDs. In the latter, the recommended time interval is >8 weeks). If for some reasons (e.g., PCV13 vaccine was not available) PPSV23 was administered first, a single shot of PCV13 should be given (when it becomes available) but at a time interval of >1 year after the administration of the previous shot of PPSV23
- If, for some reasons, PPSV23 vaccine was administered recently, the PCV13 vaccine should not be given till a minimum time of >1 year elapses. The reason is that it interferes with the development of an effective strong antibody response against the T-cell-dependent PCV13 vaccine, blunting the immune response and the uptake of the PCV13 vaccine. The mechanism could be that the highly efficient antigen-presenting B-cells, which are also the antibody-producing cells, may be “busy” in responding to the recently administered PPSV23 vaccine. Therefore, in such a situation, a time interval of > 1 year is mandatory before the administration of the PCV13 vaccine
- An especially relevant point for a country like India is that the PCV13 vaccine was not approved for adults till 2012. Therefore, many patients would have already received the PPSV23 as the first pneumococcal vaccine. Now that PCV13 has been approved and available freely, the advice for such a patient should be to administer PCV13 >1 year after PPSV23 administration (as explained above).
A pneumococcal vaccine naïve patient with AIRDs presenting to a rheumatology clinic in the age range of 19–65 years should ideally be vaccinated prior to initiating conventional synthetic disease-modifying antirheumatic drugs (cs-DMARDs). However, if the patient is already taking cs-DMARDs, she/he should still be fully vaccinated (exception for biologicals and newer small molecules, as discussed below). The patient should receive PCV13 at the first visit to be followed >8 weeks later, by the administration of PPSV23. Then, after 5 years, a second shot of (booster) PPSV23 is given. No further shots are required till the patient crosses 65 years of age when one additional shot of PPSV23 (booster) is given. No further pneumococcal vaccination shots would be required in this patient.
A pneumococcal vaccine naïve patient with AIRDs presenting to a rheumatology clinic at the age of >65 years should also be ideally vaccinated prior to initiating cs-DMARDs. However, if the patient is already taking cs-DMARDs, she/he should still be fully vaccinated (exception for biologicals and newer small molecules, as discussed below). The patient should receive PCV13 at the first visit to be followed >8 weeks later, by the administration of PPSV23. However, following the rule (number 1 above), i.e., “only a single dose of PPSV23 after the age of 65 years,” no further booster dose of PPSV23 is to be given.
A pneumococcal vaccine naïve patient with AIRDs presenting to a rheumatology clinic in the age range of 60–65 years should also be ideally vaccinated prior to initiating cs-DMARDs. However, if the patient is already taking cs-DMARDs, she/he should still be fully vaccinated (exception for biologicals and newer small molecules, as discussed below). The patient should receive PCV13 at the first visit to be followed >8 weeks later, by the administration of PPSV23. However, following the rule (number 1 above), i.e., “only a single dose of PPSV23 after the age of 65 years,” the patient should receive only a single booster dose of PPSV23 at a time interval of 5 years from the prior PPSV23 dose because by that time the patient would already have crossed 65 years of age cutoff limit.
A patient (in the age range of 19–65 years) with AIRDs presents to a rheumatology clinic. There is a history of pneumococcal vaccination, a single dose of PPSV23 in the past (due to the nonavailability of PCV13 at that time). In this case, the vaccination schedule should be as follows: a single shot of PCV13 if the time interval from the past PPSV23 is >1 year. This should be followed by a booster dose of PPSV23 5 years after the previous dose of PPSV23. The final booster dose of PPSV23 is given after the patient crosses 65 years of age ensuring that the previous booster of PPSV23 was given >5 years ago. No further pneumococcal vaccinations are to be given to this patient.
A 72-year-old female with AIRDs presents to a rheumatology clinic. There is a past vaccination history of having taken PPSV23 vaccination, when she was 66 years old. The vaccination schedule for such a patient should be as follows: a single shot of PCV13 if the time interval from the past PPSV23 is >1 year. No further pneumococcal vaccinations are to be given to this patient. Remember the rule, “Only a single dose of PPSV23 after the age of 65 years” [Figure 1] and [Table 1].
|Figure 1: Recommended schedule for pneumococcal vaccine among patients with autoimmune rheumatic diseases (Note: normal immunocompetent adults are recommended these vaccines only at age >65 years – a single shot of PCV13 followed by a single shot of PPSV23 at least after an interval of 1 year). PPSV23 = Pneumococcal polysaccharide vaccine against 23 serotypes; PCV13 = Pneumococcal conjugate vaccine|
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|Table 1: Vaccination schedule for autoimmune inflammatory rheumatic disease patients ≥19 years of age*|
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| Zoster Vaccine|| |
The incidence of HZ is increased among patients with AIRDs.,, Moreover, this problem has been amplified in the recent times since the arrival of tofacitinib, a JAK-inhibitor small molecule-targeted synthetic DMARD (ts-DMARD) interfering with intracellular signaling. Several reports have shown an increased incidence of HZ among AIRDs patients taking tofacitinib as compared to placebo, methotrexate, or biologicals.,,, Since HZ vaccine is a live attenuated vaccine, there have been concerns about its safety in immunocompromised states.,,,,,,,,,,,,,,,,,,,,,,,,,,,, In this regard, the statement in the “Green Book” in the United Kingdom The safety of HZ vaccine has been demonstrated in patients with rheumatoid arthritis (RA), even in those receiving biologicals., The HZ vaccination has become important in the Indian context also since the approval of tofacitinib (in the year 2016) for its use in patients with RA in our country. Therefore, the present-day recommendation about HZ vaccination for AIRDs patients is that they should be vaccinated with a single dose of the vaccine at >50 years of age if they did not have an episode of HZ for the past 5 years. There have been some concerns regarding the timing of vaccination vis-à-vis other vaccinations. The vaccine insert provided by the manufacturer instructs that it should not be given along with the pneumococcal vaccine based on a single manufacturer-conducted trial which showed lower antibody titers. However, a subsequent observational trial reported no difference in efficacy even if the vaccines are given on the same day together. In addition, the protection against zoster is dependent of cell-mediated immunity, and antibody titers do not seem to be protective. Thus, to avoid missed opportunities, it is prudent to follow the CDC guidelines which clearly state that both can be administered at the same time. It is to be noted that the vaccine is rather expensive. Therefore, for patients who would have difficulty in affording this vaccine, it may be reserved only for those being planned for initiating tofacitinib or cyclophosphamide and GC “pulse” therapy.
Specific recommendations for patients aged 70–79 years
Prednisolone >10 mg/day (or equivalent doses of other GC doses) for 2 or more weeks should wait 1 month before vaccination. Prednisolone >40 mg/day for >1 week in a year should wait 3 months before vaccination.
Vaccination contraindicated in patients
(a) Using mycophenolate mofetil or cyclosporine or gold preparations, (b) Cyclophosphamide given or planned within 3 months of vaccine, (c) Any antirheumatic biologic therapy.
A 59-year-old female with RA under treatment for the past 7 years recalls having had HZ in the past but does not remember when. What should be the recommendation regarding HZ vaccination? Can it be given while on cs-DMARDs? What would be the best time to give it if biological are being planned?
According to the European League against Rheumatism (EULAR) guidelines, HZ vaccine is not recommended for patients already on treatment with conventional synthetic or biological DMARDs. However, now there is extensive evidence to the contrary that, under circumstances discussed above, HZ vaccine could be safely given to patients with RA, psoriatic arthritis, and spondyloarthropathies, who are in a state of stable “low disease activity” or in “remission” on cs-DMARDs or even with biologic agents.,, The schedule should be to withhold cs-DMARDs for 1 week before vaccination and to restart 1-week postvaccination. Regarding biological, ideally, HZ vaccine should be given 4 weeks before initiating these drugs. If the patient is already taking biological, the HZ vaccine should be given at the next interval-scheduled dose of the biological as follows: 1 week for etanercept, 1 week for abatacept, 8 weeks for infliximab, and 2 weeks for adalimumab. The biological can be restarted 2 weeks after the vaccine. It should not be given to patients having had HZ in the past 5 years and should not be used in pregnancy. Thus, the final recommendation is that the patients above 50 years of age, who never had or, had HZ >5 years ago, should be vaccinated. A single shot is good for life.
| Hepatitis Vaccine|| |
The recommendations of both the ACR and the EULAR with regard to hepatitis A and hepatitis B vaccination (HBV) are only for patients with an AIRD who are “at risk” (i.e., intravenous drug users, those with multiple sex partners in the previous 6 months, or health-care personnel).,, However, recommendations in India are different. This is mainly because of a high lifetime risk of developing chronic HBV infection in our country where the estimates are that every year over 100,000 Indians die due to illnesses related to HBV infection. Therefore, for countries like India, the WHO recommends universal HBV. The launch of the Global Alliance for Vaccines and Immunization also strongly recommends intensifying National Immunization Programs (NIPs) in developing countries worldwide including community vaccination program that should include HBV vaccination. Studies by NIP have shown high cost-effectiveness of vaccination against HBV infection. The Government of India is also supporting this program. Therefore, we, the rheumatologists, should immunize our patients with AIRDs against HBV infection. The following schedule is recommended:
- History of previous vaccination: Not known
- Recommendation: Give a three-dose series at 0, 1, and 6 months
- History of previous vaccination: Only a single dose of the vaccine was given
- Recommendation: Give the second dose at least 4 weeks after the first dose; then, give the third dose at least 8 weeks after the second dose and the least dose 16 weeks after the first dose
- History of previous vaccination: Previously two doses of the vaccine were given
- Recommendation: Give the third dose at least 8 weeks after the second dose and at least 16 weeks after the first dose.
| Human Papillomavirus Vaccine|| |
Cervical cancer is one of the leading causes of cancer death among women in the world  including India.,,,,,, India, contributing 20% of the incidence of worldwide cervical cancer. A significant association with any human papillomavirus vaccine (HPV) infection and cervical cancer has been proven including in the Indian context. HPV vaccination (as part of a broader strategy which includes screening) has been calculated to be a cost-effective strategy in the Indian setting for the prevention of cervical cancer. There is a generally held notion that India is a conservative society and sexual exposure is low among adolescents. However, this misconception appears to overestimate how much of protection this affords to adolescents in India. Data from the National Family Health Survey III carried out during 2005–2006 showed that, among 46,762 adolescent women aged 15–24 years, the mean age of sexual initiation in India is 16.9 years. Only 3.2% of adolescents used barrier protection in the form of condoms during their first sexual encounter. The overall HPV prevalence in India was similar to the high-risk areas in Latin America, but lower than that observed in some parts of sub-Saharan Africa. The Indian Academy of Pediatrics Advisory Committee on Vaccines and Immunization Practices (IAPCOI) advocates routine vaccination for all patients who can afford it between the ages of 9–14 years and catch-up vaccination up to the age of 45 years. HPV4 can also be given in a three-dose series for males aged 11 or 12 years, but not yet licensed for use in males in India. Based on this information, HPV vaccination is recommended in AIRDs patients in India using the following schedule: one dose for individuals aged 9–14 years of age. One additional dose may be given at any time up to 45 years of age.
Systemic lupus erythematosus (SLE) patients are more likely to have HPV infection and an increased risk of developing cervical dysplasia and premalignant lesions. Hence, it would be prudent to vaccinate all patients with SLE at the very least. Ideally, as recommended by the IAPCOI, it should be advised to AIRDs patients in the age bracket mentioned above.
HPV vaccine can be given to patients taking cs-DMARDs, cs-DMARD combinations, tumor necrosis factor (TNF)-inhibitors, non-TNF inhibitor biological as well as tofacitinib, a ts-DMARD.
HPV recommendations from Western countries are different  as follows: Recommended for young women patients through age 26 and young men patients through age 21. It is also recommended for the following patients as well, if they were not vaccinated at younger age:
- Young men who have sex with men, including young men who were identified as gay or bisexual or who intend to have sex with men through age 26
- Young adults who are transgender through age 26
- Young adults with certain immunocompromising conditions (including HIV) through age 26.
These recommendations, however, may not be applicable as such for the Indian patients.
Biological and vaccinations
Most studies have demonstrated that Anti -TNF therapy by itself, does not affect influenza vaccine efficacy. Similar findings were found in studies in which influenza vaccine response was studied in patient on a combination of methotrexate plus a TNF-α inhibitor. In both situations though the immune response was slightly attenuated compared to controls, the antibody titre were still in the protective range. Similar to anti-TNFα therapy, anti IL-6 therapy has not found to have any clinically relevant effect on influenza vaccine efficacy. However therapy with rituximab (anti CD-20) and abatacept  substantially reduced the response to influenza vaccination. The reduced vaccine response in rituximab treated patients was seen for up to 6 months.
TNF inhibitors do not appear to have any significant influence on the immune response to vaccination. The combination of Methotrexate and TNF-α inhibitor therapy has been found to reduce the vaccine uptake. Based on the lack of any such effect in anti-TNF α inhibitor monotherapy patients and a similar reduction seen in methotrexate monotherapy patients, it can safely be assumed that this reduced uptake is due to the methotrexate in the combination.
Similar to what was seen in studies done on Influenza vaccination, anti-IL-6 therapy did not affect the immune response to pneumococcal vaccination  but anti CD-20 therapy and abatacept led to a significantly decreased response.
Vaccines and the cost calculation analysis
List of vaccinations according to the type of vaccine, manufacturer, and the price and cost calculations and analysis are provided in [Table 2], [Table 3], [Table 4].
|Table 2: List of vaccinations according to type of vaccine, manufacturer, and the price|
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|Table 3: Cost analysis for vaccinations among patients with autoimmune inflammatory rheumatic diseases - year 2017|
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|Table 4: Cost of full course of each vaccine in adult patients with autoimmune inflammatory rheumatic diseases*|
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| Conclusion|| |
Patients with AIRDs should be routinely evaluated regarding their vaccination status at the initial workup as well as in the follow-up. Ideally, they should be vaccinated during stable disease. Vaccination against invasive pneumococcal disease and flu is strongly recommended. Live attenuated vaccines (e.g. HZ vaccine) should be administered with caution, especially vis-à-vis biologicals; they should be given before initiating this treatment. In general, patients with AIRDs taking csDMARDs, low-dose GC, and TNF inhibitors can be administered all the above vaccines including the live attenuated HZ vaccine. However, for those taking immunosuppressive drugs (cyclophosphamide, azathioprine, and high-dose GC) or Bcell-depleting biologic therapy (rituximab), vaccines should be administered before initiating the treatment. It is even more important for HZ vaccine. In this regard, it needs to be emphasized that HZ vaccine is expensive. Therefore, advising it mainly for those being planned for treatment with tofacitinib or cyclophosphamide-GC high-dose intravenous “pulse” therapy may be cost-effective in Indian conditions. HBV is part of the community vaccination program of the Government of India. Therefore, it needs to be given to every patient according to the advised schedule. HPV vaccination should be considered for selected patients.
The authors would like to acknowledge Dr. Prakash Pispati's generosity in providing the book “Vaccines and Autoimmunity. Editors: Shoenfeld Y, Agmon-Levin N, Tomljenovic L” that has been very helpful in the preparation of this manuscript. Special thanks are due for the “Joint Disease Clinic” group at ISIC Superspeciality Hospital, Vasant Kunj, New Delhi, for their unstinting help and suggestions in the preparation of this manuscript. Special thanks are due to Dr. Neha Agrawal, fellow in rheumatology, for providing the vaccination-related cost analysis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]