Proceedings of the expert consensus group meeting on herpes zoster disease burden and prevention in India: An opinion paper

ABSTRACT

Herpes zoster (HZ) is a debilitating viral infection causing a dermatomal vesicular rash. Many known risk factors exist in India and adults >50 years of age may be especially susceptible to HZ. However, HZ is not a notifiable disease in India and data on incidence and disease burden is lacking. An Expert Consensus Group meeting was conducted with experts from relevant specialties to discuss HZ disease, its local epidemiology, and suggestions for implementing HZ vaccination in the Indian healthcare system. Currently, there is lack of patient awareness, poor reporting practices and general negligence in the treatment of the disease. HZ patients generally approach their general physicians or specialists for diagnosis, which is usually based on patient history and clinical symptoms. Recombinant zoster vaccine (RZV) has >90% efficacy and is recommended in adults ≥50 years of age to prevent HZ in the United States. Despite RZV being approved for use, it is not yet available in India. India has a growing elderly population with known risk factors for HZ like immunosuppression, and co-morbidities like diabetes and cardiovascular disease. This indicates the need for a targeted immunization program in India. Meeting also emphasized adult vaccine availability and accessibility in the country.

Graphical abstract

Introduction

Primary infection due to the varicella zoster virus (VZV) causes chickenpox, which affects children primarily in the pre-school age group.¹ After initial infection, VZV establishes dormancy in the sensory root ganglia of the host and may reactivate in the future. Reactivation of VZV causes herpes zoster (HZ) or shingles, which mostly affects adults and results in a painful dermatological viral infection.¹ Older adults, individuals with underlying immunocompromised conditions, and undergoing immunosuppression treatment are at an increased risk for HZ.¹ The risk of HZ incidence is also higher in patients with chronic underlying conditions like asthma, coronary heart disease, chronic obstructive pulmonary disease (COPD), diabetes, systemic lupus erythematosus (SLE) and rheumatoid arthritis.^2,3

HZ is characterized by a unilateral, painful dermatomal vesicular rash typically lasting for 7 to 10 days, usually healing within 2 to 4 weeks among immunocompetent individuals.¹ Pain caused by HZ is typically characterized as aching, burning, stabbing, or shock-like and disrupts the daily activities and overall quality of life of HZ patients.¹ One of the most frequent complications of HZ is post-herpetic neuralgia (PHN), defined as pain that persists for at least three months from onset of the rash.⁴ While HZ is a vaccine-preventable disease, and two vaccines (live attenuated varicella-zoster virus vaccine and recombinant zoster vaccine [RZV]) are available in many countries,⁵ there are currently no HZ vaccines available in India.

In India, HZ is not a notifiable disease and there is a lack of comprehensive evidence which describes the incidence and healthcare burden of the disease.⁶ Studies in India suggest that majority of the cases were observed in patients >50 years of age, with PHN and secondary bacterial infections being the most commonly reported complications.⁶ Given the lack of information on the clinical profile of HZ in India, the limited available data suggests that HZ could be a major health burden to the elderly population in the country.

Materials and methods

Meeting objectives

Primarily, there is a paucity of information on the incidence of HZ cases, its epidemiology, and the burden of disease on public health in India. With a growing elderly population in India and a wide prevalence of HZ risk factors, the meeting explored the benefits of HZ vaccination programs, especially immunocompromised adults and adults >50 years of age with co-morbidities who are at-risk of disease. Generally, HZ patients are diagnosed by a general physician (GP) or a specialist, based on patient history and clinical symptoms. Thus, an Expert Consensus Group consisting of GPs and various specialists (including dermatologists, pulmonologists, diabetologists, immunologists, infectious disease specialists, and gynecologist among others) was organized to assimilate data on current disease epidemiology, treatment gaps, and relevance of vaccination among the older adults with co-morbidities and healthy adults >50 years of age. The expert group also evaluated the newly launched RZV (Shingrix (GSK; Belgium)), which is approved for use in India, for prevention of HZ and PHN in adults 50 years of age or older. The panel comprised of 12 practicing physicians from different parts of the country and facilitated by the GSK Vaccines Team. The Expert Consensus Group meeting was conducted in a hybrid format (face-to-face and virtual) on July 3, 2022, in Mumbai. The representatives from GSK introduced RZV and moderated the sessions where the experts discussed HZ disease and its local epidemiology, the clinical profile of RZV along with suggestions of use, and barriers to vaccine implementation among the adult population. The expert opinions are outlined in this paper.

Results and discussion

Meeting output

HZ disease and epidemiology

The Group was united in their opinion that HZ (including its associated complications such as PHN) is a painful, debilitating disease mainly afflicting elderly patients, resulting in substantial morbidity in India. Unfortunately, no population-based studies have been carried out to estimate HZ disease burden in India which was highlighted by discussing presently available literature for the region. Notably, the average HZ incidence was reported to be 5.0 per 1000 person-years (PY) in Asia.^6,7 On grouping based on age, the incidence values were estimated to be 2.0–3.1, 4.3–5.2, and 7.4–13.8 per 1000 PY in those aged 0–20, 20–50, and >50 years of age, respectively.^6,7 Studies also indicated that the geographic location had minimal impact on HZ incidence, which was comparable to different regions of the world.^6,8–11 A systematic review of HZ cases in India reported a range of 18 to 938 clinical HZ cases between January 2011 and May 2020, with the majority of cases seen in adults >50 years of age.⁶ Pain was reported to be the most common symptom of the disease, with the majority of the patients reporting burning pain,^12–15 while many patients also reported a rash in the thoracic dermatome.¹⁵ The most commonly reported complication among HZ patients in India was PHN.¹² Three separate studies reported a higher concentration of PHN among older adults^13,14,16 and two more in immunocompromised patients.^17,18

The experts discussed the patient pathway for HZ in India, including the specialties best suited to manage the disease. A review of current treatment protocols and strategy to reduce HZ incidence was explored. They also analyzed the risk factors for HZ, the age group most susceptible to HZ and associated complications.

It was the Group’s opinion that most HZ patients visited their GPs, dermatologists, or other specialists during symptom onset. Given that diabetes is highly prevalent in India and a risk factor for HZ,^19,20 patients may also approach diabetologists with their symptoms. Currently, diagnosis is based on patient history and clinical symptoms presented to the GP/specialist, specifically the characteristics and location of the rash.²¹ Clinical diagnosis is rarely reconfirmed with laboratory testing via Tzanck smear or polymerase chain reaction. It was also noted that patients were usually under-prescribed medications or lacked adherence to their prescriptions, which affected their quality of life. The experts encouraged segmentation of patients into four groups: (I) healthy patients, (II) patients with co-morbidities like diabetes, COPD, SLE etc., (III) immunocompromised patients (IV) and healthcare practitioners. The rationale for including healthcare practitioners as a patient group was the risk of contracting varicella due to close contact with HZ patients. The Expert Group determined that these four groups were at a greater risk of exposure to both VZV and HZ. Such segmentation of the risk groups could help to efficiently care for HZ patients.²²

The literature suggests that the risk of HZ incidence increases with age, especially for those >50 years of age.^23,24 Apart from age, the presence of concomitant diseases like diabetes mellitus, chronic obstructive pulmonary disease (COPD), systemic lupus erythematosus, and cardiovascular diseases have been reported to increase the incidence and severity of HZ in older adults.^25–29 Patients with diabetes mellitus were 1.6 times more likely to develop HZ than patients without diabetes mellitus.^30–32 Similarly, the HZ incidence rate in patients with COPD has been reported to be approximately four times higher compared to patients without COPD.^33,34 As there has been a steady increase in the prevalence of chronic non-communicable disease during the past decades, management of such diseases could positively impact HZ incidence.^35,36 Vaccination in older adults with co-morbidities could help achieve this by reducing the risk of HZ incidence in the target population.

The Expert Group noted the need to streamline the vaccine prescription pathway in India such that individuals may obtain the prescription efficiently. This could be carried out with the cooperation of consulting physicians from different specialties such as dermatology, diabetology, nephrology, and gerontology by prescribing the HZ vaccine to at-risk patients. Lastly, the Group emphasized that a collaborative approach including GPs, dermatologists, and diabetologists would enhance the understanding of treatment, diagnosis, and prevention of HZ disease in the country while also spreading patient awareness.

RZV clinical profile and expert opinions

Zoster vaccine live (ZVL), a live attenuated virus, was initially recommended by The Advisory Committee on Immunization Practices (ACIP) for adults over 60 years of age in 2008.³⁷ In October 2017, a non-live adjuvant RZV (Shingrix) vaccine against HZ in adults >50 years of age was licensed by the Food and Drug Administration in the United States. Following which in 2018 the ACIP changed its preferred recommendation for adults >50 years of age to the RZV based on the safety and efficacy data.³⁸ Subsequently in 2022, the RZV has also been approved for use in India.³⁹ It is recommended to be delivered intra-muscularly in two doses, two to six months apart.⁴⁰ The vaccine was found to have a clinically acceptable safety profile and high immunogenicity. Additionally, the vaccine had a > 90% efficacy rate in both 50- and 70-year-old populations for 3.2–3.7 years post-vaccination.^41,42 Injection site pain was the most commonly reported general adverse event among others including myalgia, headaches, shivering, fever, stomachache, and nausea.⁴³

The Expert Group discussed the safety and efficacy data of the RZV vaccine. In addition, the group focused on increasing awareness about the vaccine and improving compliance with the second dose.

The Expert Group agreed that all at-risk patients >50 years of age with preexisting health conditions like COPD, diabetes, cardiovascular diseases, chronic renal disease, SLE etc., should be vaccinated against HZ. Although not currently licensed in India, the expert panel suggested formulating immunization guidelines for younger adults at risk due to an immunocompromised condition such as rheumatic disease, human immunodeficiency virus, and other auto-immune diseases. It was also proposed that patients be made aware of the side effects of RZV vaccination. Based on their clinical experience, the panelists proposed prescribing anti-inflammatory or analgesic medications to increase compliance for the second dose. Among healthy individuals >50 years of age, GPs could share the decision-making process with the patients after counseling them on the disease and benefits of vaccination. To facilitate this, increasing awareness of GPs and other physicians was endorsed, either with continuing medical education programs or adult immunization workshops during symposia or medical conferences.

The Group also validated patient awareness and optimal health communication as important factors in successfully implementing HZ immunization among older adults. Supplementing patient awareness through digital and print media in clinic waiting rooms and introducing adult immunization cards could increase patient awareness. However, GP awareness of the disease and vaccine benefits was prioritized by the Group over patient awareness and health communication as patients typically followed the advice of their family GP over the media.

In addition, the Group reiterated the importance of guidelines recommended by medical societies to have a high impact on vaccine awareness in the long term. Public awareness of HZ as a vaccine-preventable disease could also be ensured by engaging with patients during preventive health checkups, corporate health camps, and other such periodic events.

RZV in the Indian setting

The Expert Group evaluated the best approach to increase awareness among the patients and the GPs about the HZ disease and vaccine. Barriers in the implementation of a vaccine program were also discussed.

The Expert Group recognized the role of GPs in the successful implementation of a vaccination program. Convincing GPs of the importance of vaccination against HZ was paramount as it would encourage them to discuss the significance of vaccination with their patients. Many GPs hesitate to recommend adult vaccination because of the inconvenience of biomedical waste disposal, upkeep of vaccine cold-chain, and fear of side effects and legal claims. To combat these fears, it was suggested that healthcare organizations could reassure GPs by aiding in the logistics of vaccination.

Other than GPs, cardiology, nephrology, oncology, and rheumatology were identified as the ideal specialties to focus on implementing the HZ vaccine efficiently. These specialties serve a smaller patient pool, most of which have a higher chance of contracting the disease and suffering from its complications.

The Group also discussed that patients tend not to follow through if the vaccination process is highly complicated. It was suggested that the vaccination process be streamlined by vaccinating at-risk inpatient cases with first dose before discharge and the second dose during their follow-up visit. In this way, the vaccination costs may be covered by the patient’s health insurance. Lastly, the Group highlighted the lack of awareness of all adult vaccines and the importance of increasing vaccine availability within the healthcare system.

Future aspirations

During the meeting, HZ epidemiology and the prevalence of HZ were discussed. Since HZ is not a notifiable disease in India, there is a lack of information on the prevalence of HZ and the overall disease burden. As a result, patient awareness about HZ is lacking and milder forms of HZ are generally neglected. Further studies on HZ incidence and associated healthcare burden would be helpful in developing an adult vaccination program in India. The vaccination of healthy and at-risk patients >50 years of age can help reduce the number of HZ cases and potentially reducing the cumulative disease burden in the population. During the meeting, the Expert Group discussed HZ epidemiology and treatment in India, HZ vaccinations, and recommendations for a successful vaccination program in the country. The meeting concluded by highlighting the need for increasing availability and accessibility of adult vaccines in India.

Funding Statement

GlaxoSmithKline Biologicals SA funded all costs associated with the development and publication of this manuscript.

Disclosure statement

NL, YL and YC are employed by, and hold shares in GSK. AV reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events. NL, YL, YC and AV declare no other financial and non-financial relationships and activities. VR declares no financial and non-financial relationships and activities and no conflicts of interest.

Trademark

Shingrix is a trademark owned by or licensed to GSK.