https://orcid.org/0000-0003-3125-9114
ABSTRACT
Although 1 in 3 people globally are expected to develop herpes zoster (HZ; i.e. shingles), HZ vaccination is not currently part of the Philippine National Immunization Program and HZ is not considered as one of the main vaccine-preventable diseases highlighted by the Department of Health. We report the findings from two advisory boards held with healthcare professionals (HCPs) to understand the current landscape of HZ management and prevention in the Philippines. The first advisory board focused on the management and prevention of HZ in patients aged ≥50 years, the second in immunocompromised patients aged ≥18 years. HCPs reported seeing HZ cases across specialties, with the most common complication being postherpetic neuralgia. HZ was reported to impose a substantial burden on patients, due to both the cost of treatment and distress caused due to pain. HZ could also complicate the treatment of ongoing conditions. HCPs agreed that the introduction of the recombinant zoster vaccine, which was recently approved by the Philippines Food and Drug Administration, could help in the prevention of HZ, addressing the needs of both HCPs and patients. Suggested steps to establish HZ vaccination in the Philippines included improved HCP and patient education, and establishing local HZ vaccine recommendations.
Introduction
Herpes zoster (HZ), also known as shingles, is caused by reactivation of varicella zoster virus (VZV).Citation1,Citation2 Patients with HZ can present with a range of manifestations, the most common being a painful localized vesicular unilateral rash.Citation1–3 HZ can also cause serious complications, such as long-term nerve pain (i.e. postherpetic neuralgia [PHN]) which can negatively impact patients’ quality of life and lead to socioeconomic burdens through productivity losses and considerable healthcare costs.Citation1,Citation3
Approximately 1 in 3 people will experience HZ in their lifetime.Citation1,Citation2 Due to reduced cellular immunity, older adults and those with immunocompromising conditions are at greater risk of developing HZ.Citation1,Citation4,Citation5 As the global aging population grows,Citation2 the incidence of HZ will also likely increase. This is projected to cause significant economic strain on healthcare systems.Citation6,Citation7
Although effective vaccines for HZ have been developed, adult immunization has not taken precedence in the Asia-Pacific region, with the majority of immunization policies targeted toward children.Citation1,Citation8 However, the population of people aged over 60 years in Asia is expected to reach almost 1 billion people by 2035, which is estimated to be reflected in 30,395 new cases of HZ daily.Citation1
In the Philippines, the data on the burden of HZ are relatively limited, as highlighted by a systematic literature review (SLR) of the burden of HZ in Southeast Asia.Citation9 One study identified in this literature review, conducted in the Dermatology department of a hospital in Manila, demonstrated the prevalence of complications in HZ patients, with 75.1% of 221 identified HZ patients reporting HZ-associated pain, 6.8% reporting secondary bacterial infections and 5.0% reporting ophthalmic involvement. Data from 11 dermatology institutions in the Philippines have shown an increasing prevalence of HZ, from 664 in 2011 to 1,359 in 2017.Citation10
The live-attenuated HZ vaccine (zoster vaccine live [ZVL]; Zostavax [Merck]) was available in the Philippines for protection against HZ until 2020. An alternative vaccine, recombinant zoster vaccine (RZV; Shingrix [GSK]) has been approved by the Food and Drug Administration in the Philippines and is currently undergoing an initial monitored release.Citation11 Although safety and efficacy data for both vaccines support their use for the prevention of HZ in older healthy adults, there is some evidence that RZV may prevent more cases of HZ than ZVL in those aged ≥50 years.Citation12 Additionally, RZV is not contraindicated in immunocompromised patients as it is not a live vaccine.Citation3
In order to further understand the current landscape of HZ management and prevention in the Philippines, two advisory board meetings comprised of expert healthcare professionals (HCPs) in the Philippines were convened to discuss the following key topics surrounding HZ: The current disease burden and management of HZ in the Philippines, challenges and barriers to immunization, and future steps to improve awareness of the importance of vaccination against HZ.
Proceedings
Advisory board setting
Two advisory boards took place in Manila, Philippines on the 23rd and 30th September 2022. The first focused on the management and prevention of HZ in patients aged ≥50 years, the second in in patients aged ≥18 years who are immunocompromised. The experts came from a range of specialties, summarized in .
Table 1. HCP specialties.
Discussion points
A set of predetermined questions were used to guide the discussion of the advisory boards to seek advice from the experts. Some questions differed between the first and second advisory boards (see below):
Epidemiology and burden of disease
Is the epidemiology described aligned with your practice?
How often do you see HZ in your practice?
What are the common complications of HZ that you see?
How do these complications affect your patients?
Challenges in herpes zoster management
Advisory board 1
With the current treatment approach to HZ, what are the challenges specific to your practice?
How do you address these challenges?
How will RZV vaccination help address these challenges?
Advisory board 2
Where is the initial point of consultation among adult immunocompromised patients with HZ? How are these patients managed?
What are the challenges in HZ management specific to your practice?
How will RZV vaccination help address these challenges?
Adult immunization
Can you share your experience of adult immunization among those aged ≥50 years (advisory board 1)/immunocompromised patients ≥18 years (advisory board 2)?
Do you recommend vaccines to all your patients?
If not, which specific priority groups do you recommend vaccination to?
What motivates patients to seek vaccination?
What are the challenges in achieving higher vaccination rates from your experience?
Can you describe the patient journey of the following groups for adult immunization?
Immunocompetent adults with/without comorbidities and the elderly (advisory board 1)
Immunocompromised patients who are ≥18 years old (advisory board 2)?
Herpes zoster vaccination
Have you had any experience with HZ vaccination in your routine practice, including post-HZ patients?
If yes, where were your patients vaccinated?
To which patients (age, co-morbidities present) did you prioritize vaccination against HZ?
What else do you tell your patients?
If RZV becomes available, will you recommend vaccination to your patients?
If yes, will you be the one to administer the vaccine, or will you refer your patient for vaccination elsewhere? Where will you refer them?
If no, why?
Clinical practice guidelines for herpes zoster immunization
Are you aware of any local or international clinical practice guidelines for immunization for your specialty?
If yes, is vaccination against HZ included?
Can you share the acceptance of these guidelines by the members of your society?
If none, is there an opportunity to get local guideline recommendation for HZ vaccination? What evidence would be needed to support this?
Compliance to herpes zoster vaccine schedule
Will compliance to a two-dose vaccine like RZV be a challenge?
How do we address this challenge?
Actions
What actions are needed to drive the urgency to vaccinate against HZ among patients ≥50 years (advisory board 1), immunocompromised patients ≥18 years (advisory board 2) and HCPs?
Which of these would be the most important?
What can be done by you as a specialist and by your society to improve immunization uptake among ≥50 years patients (advisory board 1) and immunocompromised patients ≥18 years (advisory board 2)?
What do you think are the best approaches in terms of messages and channels for HZ education in the Philippines, for HCPs and the lay audience?
Key findings from the experts
Disease burden and management of herpes zoster in the Philippines
Frequency of herpes zoster cases seen by specialists
In the Philippines, there is a lack of strong local data on HZ epidemiology and prevalence at a national level, as highlighted by a recent SLR, although some case studies and single-center studies were identified.Citation9 The experts highlighted that this is particularly true for HZ in immunocompromised patients.
As HZ presents with a range of clinical manifestations, it can overlap clinical boundaries and involve the care of different specialties.Citation1 While the frequency of HZ cases seen by the HCPs varied by specialty, the experts agreed that HZ patients were most commonly seen by geriatricians or dermatologists. It was also agreed that PHN was the most common complication of HZ seen in the clinic.
Herpes zoster patient pathway
Older adults with HZ were reported to be typically seen by geriatricians across outpatient, nursing/retirement and occasionally hospital settings. Often, diagnosis of HZ might be complicated by atypical presentations (e.g. uncommon location and unusual pain). A stepladder approach in the management of acute pain was reported to be helpful for older patients. According to the experts, PHN in older patients is often managed through a slow titration of a combination of several medications at low doses where pain control is usually achieved within 3 months.
Patients across age groups were reported by dermatologists to present with the classic HZ symptomatology, alongside HZ ophthalmicus and zoster sine herpete. Management of PHN included compresses, antivirals, analgesics and a short course of corticosteroids. Patients not responding to usual analgesics were referred to neurologists who may then utilize a multi-modal strategy with centrally-acting medications in their management.
On occasions where HZ presents in the prodromal phase in patients with an underlying chronic condition, patients may be seen by specialists such as pulmonologists, cardiologists or endocrinologists. Management of their underlying chronic disease may be complicated by HZ, necessitating adjustments in medications.
As noted in the second advisory board, certain treatments such as steroids, chemotherapy and targeted therapies can increase the risk of VZV activation in immunocompromised patients. In these patients, antiviral prophylaxis may be recommended to prevent VZV reactivation (e.g. in hematopoietic stem cell transplantation [HSCT] patients).
Challenges in herpes zoster treatment
One challenge of HZ treatment faced in Philippines is its high cost. Based on the insights shared by an expert who attended one of the advisory board meetings, the estimated treatment cost of complicated zoster is approximately PHP 21,000 for diagnostic tests and PHP 150,000 for antivirals in a private tertiary hospital. For a government tertiary hospital, the cost was estimated to be around PHP 50,000 for a 14-day treatment of antiviral drugs (acyclovir) and peripherals for infusion. In addition, PHN can often linger for a long time which, aside from causing distress to patients, can prolong the length and costs of treatment. These high medication costs can also add to the financial burden of middle-lower income individuals or individuals who are already receiving additional medication for other conditions.
Aside from cost, HZ management strategies may come with side effects and a high pill burden which can impact patients’ quality of life. This is especially true in elderly and immunocompromised patients.
In immunocompromised patients or patients being treated for other conditions, one additional challenge is that HZ signs and symptoms may be missed, such as rashes being misdiagnosed as a flare up of systemic lupus erythematosus or HZ-related pain thought to be a complication of chemotherapeutic drugs. HCPs treating patients with immunocompromising conditions must also consider the balance of immunosuppressive drugs that treat a condition versus increasing patients’ risk of developing HZ.
Experience with adult and herpes zoster vaccination
Experience with adult immunization
Adult immunization in the Philippines varies by specialty, but the experts highlighted that influenza, pneumococcal, human papilloma virus and hepatitis vaccinations are the most common. In both advisory boards, 8 out of 9 experts had experience with adult vaccination. The details of vaccine administration experiences from the experts are summarized in .
Table 2. Expert experience with vaccination.
Experience with herpes zoster vaccination
Only some of the clinicians in these advisory boards had personal experience vaccinating against HZ with ZVL. Notably, ZVL is contraindicated to immunocompromised patients as it is a live vaccine.Citation2 Therefore, the experts in the second advisory board discussing HZ vaccination in immunocompromised patients are often unable to provide vaccination, despite some patients actively seeking out HZ vaccination. As immunocompromised patients are at a higher risk of developing HZ, they would therefore benefit from access to a suitable vaccine.
The experts highlighted the lack of clinical practice guidelines for HZ vaccination. The Philippine Periodic Health Examination (PHEX) taskforce, assembled by the Philippines Department of Health, recommend HZ vaccination among immunocompetent patients aged ≥60 years. However these guidelines primarily discussed ZVL as RZV was not yet available locally.Citation13 Only three specialties – infectious diseases, geriatrics and obstetrics – had local adult immunization recommendations, including HZ vaccination for patients aged ≥50 years. Regarding patients with immunocompromising conditions, only one specialty, gyne-oncology, had access to local immunization guidelines for HZ.
HZ vaccination is not currently part of the Philippine National Immunization Program and HZ is not considered as one of the main vaccine-preventable diseases highlighted by the Department of Health.Citation14 Some experts highlighted that they adopt clinical practice guidelines from other local or international societies, such as the United States Center for Disease Control Advisory Committee on Immunization Practices (ACIP) recommendations, when local vaccination guidelines are not available from their own respective societies.
The experts in the advisory boards agreed that the introduction of RZV into the Philippines would help to overcome management challenges in their clinical practices by preventing HZ and its resulting complications. Additionally, HCPs who treat immunocompromised patients also agreed that the introduction of RZV would help to reduce the burden of HZ more than the use of antiviral prophylaxis alone. It was agreed that once RZV is available in the Philippines the experts would likely recommend the vaccine to their relevant patients, with one expert stating that they would administer RZV themselves or refer patients to a vaccination hub.
Challenges to herpes zoster vaccination
Patient barriers to vaccination
In addition to ZVL no longer being available, the uptake of HZ vaccination in the Philippines has been limited due to a range of barriers. For patients, the economic costs of HZ vaccination was highlighted as a barrier as the government does not cover the cost of HZ vaccination in the Philippines. Additionally, HZ vaccine and disease awareness may be low or not considered a priority by certain patients, especially those aged ≥80 years with end-of-life illnesses.
Compliance to the two-doses of the RZV vaccine may also be a barrier due to the cost of the second-dose and patient forgetfulness. Suggested actions to mitigate these factors included implementing reminder systems for HCPs and patients with electronic medical records, incorporating immunization recommendations during follow-up consultations for chronic illnesses, and educating patients on the importance of receiving both doses.
Access to and availability of HZ vaccines was also identified as a barrier. In the past, a consistent availability of ZVL from vaccine distributors was an immediate issue regarding vaccine uptake in Asia.Citation1 In addition, the logistics of receiving vaccinations may be difficult for patients with physical limitations and mobility issues. These patients could benefit from receiving HZ vaccinations in their homes, or having HZ vaccinations available from pharmacies.
Patients with immunocompromising conditions may also be concerned about how the vaccine could interact with other medications they are receiving.
Healthcare professional barriers to vaccination
For HCPs, the intricacies and challenges involved in implementing and maintaining the infrastructure and ensuring consistent vaccine supply for in-clinic vaccination, such as cold chains, taxation requirements and vaccine monitoring may act as barriers.
In addition, depending on the specialty, clinicians may have limited experience of HZ vaccination or knowledge of local vaccine guidelines. One of the oncologists participating in the advisory boards reported that an online survey conducted by a local medical oncology society found that only 11% of respondents had attended a lecture on vaccination and that 95% were unaware of any local guidelines on vaccination.
The lack of local guidelines was also a key barrier expressed by the experts. Experts also expressed that they would appreciate more specific recommendations on the timing of HZ vaccination, such as whether HZ vaccination should take place after an acute episode of HZ to prevent recurrences and when HZ vaccines should be administered relative to immunosuppressive treatment.
Driving reasons patients may wish to get vaccinated against herpes zoster
The experts outlined several reasons as to why patients may wish to get vaccinated against HZ. For example, the general population may have the desire to be vaccinated if they have witnessed a family member or have themselves previously experienced HZ and its complications. Additionally, the general population may have increased awareness of the importance and benefits of adult vaccination since the COVID-19 pandemic. For working adults, the concerns surrounding productivity losses due to absence from work may be a key reason to receive vaccination, and certain companies may provide immunization to employees as a benefit to reduce absenteeism. For patients with immunocompromising comorbidities, vaccines may be more readily accepted as these patients may have an additional drive to avoid the burden of disease.
Discussion
The experts who participated in this advisory were all aligned regarding the benefit HZ vaccination would bring to elderly and immunocompromised patients in the Philippines. They highlighted cost of vaccination, low disease awareness, a lack of strong local guidelines and challenges in maintaining vaccine infrastructure as key barriers for HZ vaccine implementation.
Suggestions on how to overcome barriers to HZ vaccination for patients included improved education on the burden of HZ and benefit of vaccination, which could be achieved through patient groups, social media, and use of infographics. Additionally, tools such as a second-dose reminder on patients’ phones and adult immunization booklets to track received vaccine doses, as well as offering multiple non-live vaccines in one clinic visit could be used to increase second-dose compliance. Staggered payment options or payment plans were also suggested to improve uptake.
Educating HCPs in the Philippines on vaccination guidelines, efficacy and vaccinology principles was highlighted as being highly important to improve confidence in making strong recommendations for HZ vaccination. This will empower HCPs to confidently discuss not only the benefits of vaccination to their patients but also the possible vaccine side effects and interactions, and enable them to answer questions on misinformation especially regarding ‘antivaxx’ information. Capacity building and increased support for vaccine infrastructure is also crucial for enabling HCPs to start vaccination in their practice. With the improved infrastructure, vaccination could be offered at primary care facilities and dermatology centers.
The experts also emphasized the need for strong guideline recommendations in the Philippines and the development of specialty-specific recommendations for immunocompromised patients, including recommendations on the timing of vaccine administration. The experts suggested that a collaborative, multi-specialty, special interest group to address the issues and challenges of vaccination in the Philippines would be helpful for formulating vaccine-specific recommendations for the region.
Conclusions
The burden of HZ in the Philippines is substantial and projected to increase. Current HZ management strategies such as antivirals may incur high costs to the patient on top of unwanted side effects. In addition, antivirals do not prevent the occurrence of complications such as PHN. The experts in this advisory board were in agreement that HZ vaccination would benefit the needs of their patients. The steps that must be taken to establish HZ vaccination in the Philippines include improved education on the disease burden of HZ and the benefits of HZ prevention. For HCPs to confidently advocate for HZ vaccination, local guideline recommendations on HZ vaccine administration and timing must be implemented.
Authors’ contributions
Substantial contributions to study conception and design: MP, MCR, RZ, GZ, GLB, ADA and JJ; substantial contributions to analysis and interpretation of the data: MP, MCR, RZ, GZ, GLB, ADA and JJ; drafting the article or revising it critically for important intellectual content: MP, MCR, RZ, GZ, GLB, ADA and JJ; final approval of the version of the article to be published: MP, MCR, RZ, GZ, GLB, ADA and JJ.
Acknowledgments
The authors acknowledge Dr Eduardo Aro Jr, Dr Ivy Mae Escasa, Dr John Paulo Vergara, Dr Lilli May Cole, Dr Maria Gina Nazareth, Dr Rodolfo Pagcatipunan, Dr Leilani Senador, Dr Eduardo Poblete, Dr Cheridine Oro-Josef, Dr Lonabel Encarnacion, Dr Ricardo Manalastas Jr, Dr Kris Lodronio Lim, Dr Mary Queen Florencio and Dr Artemio Roxas for their contributions to the advisory board meetings and Bella Dragova, GSK, Belgium for publication management. The authors also thank Costello Medical for editorial assistance and publication coordination, on behalf of GSK, and acknowledge Kaity McCafferty Layte, Costello Medical, UK for medical writing and editorial assistance based on authors’ input and direction.
Disclosure statement
MP, RZ, GZ: Received fees from GSK for participation in this advisory board.
MCR: Received payment from GSK for participation in a GSK Vaccination Masterclass, participated in GSK advisory boards and is the Chair of the Adult Immunization Committee of the Philippine Society for Microbiology and Diseases.
GLB, ADA and JJ: Employees of GSK.
Data availability statement
Data sharing not applicable to this article as no datasets were generated or analyzed during the current work.
Additional information
Funding
References
- Chen LK, Arai H, Chen LY, Chou M-Y, Djauzi S, Dong B, Kojima T, Kwon KT, Leong HN, Leung EMF, et al. Looking back to move forward: a twenty-year audit of herpes zoster in Asia-Pacific. BMC Infect Dis. 2017;17(1):213. doi:10.1186/s12879-017-2198-y.
- Harbecke R, Cohen JI, Oxman MN. Herpes zoster vaccines. J Infect Dis. 2021;224(12 Suppl 2):S429–7. doi:10.1093/infdis/jiab387.
- Patil A, Goldust M, Wollina U. Herpes zoster: a review of clinical manifestations and management. Viruses. 2022;14(2):192. doi:10.3390/v14020192.
- Gagliardi AM, Andriolo BNG, Torloni MR, Soares BGO, de Oliveira Gomes J, Andriolo RB, Canteiro Cruz E. Vaccines for preventing herpes zoster in older adults. Cochrane Database Syst Rev. 2019;2019(11). doi:10.1002/14651858.CD008858.pub4.
- Kawai K, Gebremeskel BG, Acosta CJ. Systematic review of incidence and complications of herpes zoster: towards a global perspective. BMJ Open. 2014;4(6):e004833. doi:10.1136/bmjopen-2014-004833.
- Varghese L, Standaert B, Olivieri A, Curran D. The temporal impact of aging on the burden of herpes zoster. BMC Geriatr. 2017;17(1):30. doi:10.1186/s12877-017-0420-9.
- Warren-Gash C, Forbes H, Breuer J. Varicella and herpes zoster vaccine development: lessons learned. Expert Rev Vaccines. 2017;16(12):1191–201. doi:10.1080/14760584.2017.1394843.
- Isahak I. Adult immunization–a neglected issue in Southeast Asia. Southeast Asian J Trop Med Public Health. 2000;31(1):173–84.
- San Martin P, Aunhachoke K, Batac MCF, Lodrono-Lim K, Kwanthitinan C, Santoso D, Fonseka T, Nguyen M, Guzman-Holst A. Systematic literature review of herpes zoster disease burden in Southeast Asia. Infect Dis Ther. 2023;12(6):1553–78. doi:10.1007/s40121-023-00822-0.
- Philippines Dermatological Society. Philippines dermatological society health information system 2019. [accessed 2023 Jun].
- Food and Drug Administration Philippines. Human drugs - herpes zoster vaccine (recombinant, adjuvanted) 2023. [accessed 2023 Aug]. https://verification.fda.gov.ph/drug_productsview.php?showdetail=®istration_number=BR-1441.
- Tricco AC, Zarin W, Cardoso R, Veroniki A-A, Khan PA, Nincic V, Ghassemi M, Warren R, Sharpe JP, Page AV, et al. Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: systematic review and network meta-analysis. BMJ. 2018;363:k4029. doi:10.1136/bmj.k4029.
- National Institutes of Health - Institute of Clinical Epidemiology. Philippine guidelines on periodic health examination: immunization for adults 2021. [accessed 2023 Aug]. https://drive.google.com/file/d/15bZXoiltUJxGMlp5wgOMxI70tY6PTplE/view.
- Republic of Philippines Department of Health. National immunization program manual of operations 2021. [accessed 2023 Aug].