Herpes Zoster Hospitalizations in Italy

Herpes Zoster Clinical Trial

Official title:

Nationwide Retrospective Observational Study of Herpes Zoster Associated Hospital Admissions in Italy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05952271
• Other study ID #: 14112
• Status: Recruiting
• Start date: October 26, 2023
• Est. completion date: July 30, 2025

Study information

• Verified date: October 2023
• Source: University of L'Aquila
• Contact: Antonella Mattei, PhD
• Phone: +390862434651
• Email: antonella.mattei[@]univaq.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In Italy, the 2017-2019 National Immunization Plan recommended specific vaccinations for the elderly, defined as those 65 years old and older, and at-risk adults with age 50+ (adults presenting cardiovascular, respiratory, or metabolic diseases, immunodepression, etc.). However, the coverage target set by the Plan (50% for Herpes Zoster vaccination in 2019) was not reached.

Providing additional data on the incidence of Herpes Zoster could improve the risks perception of the disease and the vaccination uptake. The present study will aim to describe a full picture of Herpes Zoster associated hospital admissions in Italy, focusing on co-morbidities which induce reduced varicella-zoster virus-specific cell-mediated immunity response. Furthermore, as varicella-zoster virus reactivation was reported in COVID-19-positive patients, a deepening on a possible relationship between the two infections will be investigated.

Description:

Varicella (chickenpox) is a highly contagious illness sustained by an α Herpes virus called varicella-zoster virus (VZV). A replication phase in the penetration site is followed by a viremic phase when VZV spreads to skin and mucosae, leading to the typical rash and infection of sensory nerves in the epithelium, and then the reach of the sensory ganglia where it becomes latent. The reactivation of the latent virus, years or decades after primary infection, causes the typical clinical expression called Herpes Zoster (HZ) or shingles.

Post-herpetic neuralgia (PHN), an intractable pain in the dermatome affected by HZ, is the most common complication. It is estimated that it affects 10-20% of all patients with HZ aged ≥ 50 years and up to 30% of those aged ≥80 years. Management of PHN is not easy, but vaccination for prevention of PHN may be a strategic choice.

The most common complications of herpes zoster, other than PHN, often requiring hospitalization, include secondary bacterial infections, ophthalmic complications, cranial and peripheral nerve palsies, and segmental zoster paresis.

All authors agree that factors such as age, cell-mediated immunity (CMI) depression, intrauterine exposure to VZV and varicella occurring in early age (<18 months) are typically associated with HZ incidence. It further should be noted that age and CMI depression are strictly related since increasing age leads to CMI decrease. An increased incidence of hospitalization for HZ among patients aged >72 years (0.46/1000-person year), compared to those aged 15-44 years (0.03/1000-person year) was reported, suggesting that aging is also a risk factor for HZ requiring hospitalization. Besides age, HZ risk can be related to other co-morbidities, including diabetes, major depression or immunosuppressive therapies, that induce reduced VZV-specific CMI response. Immunosuppressed patients are within the high-risk group, with increasing morbidity and mortality associated with herpes zoster. Immunosuppression may be associated with malignancy (especially hematological), human immunodeficiency virus (HIV) infection or medications used for organ transplantation or autoimmune disease.

HZ incidence is similar all over the world and its trend is related to population age, with two thirds of the cases affecting subjects aged >50 years.

Among European adult population, the percentage of subjects estimated to be seropositive for anti-VZV antibodies is 95%: all of them are therefore potentially susceptible to develop HZ in their lifetime. In Italy, the annual incidence of HZ is 6.3/1000 person-years, with 73% of cases affecting adults.

Italy is one of the countries with the highest proportion of elderly people in its population, and yet data on the epidemiology of HZ and PHN are limited. As the immune system weakens with increasing age, many infectious diseases, such as HZ, are more severe and more closely associated with long-term consequences in the elderly than in younger people. With the growing aging population, a rise in the number of cases of HZ in the near future is expected; thus, this disease will become a public health issue. While awareness of childhood vaccination is well established, the prevention of infectious diseases in groups other than children is a challenging, yet fundamental, objective that public health systems should pursue in order to promote healthy aging.

In order to evaluate the epidemiological burden of HZ, hospital discharge records for HZ between 2011 and 2021, with or without complications, will be extracted from the national hospital discharge database (HDD).

The characteristics of hospitalizations will be described for the 18 years of age and older adults (2011-2021 years).

The characteristics of hospitalizations in 2020-21 will be described in patients with or without concomitant COVID-19 infection.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72000
• Est. completion date: July 30, 2025
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Hospital discharge records for Herpes Zoster infection in primary diagnosis age =18 years

• Hospital discharge records for Herpes Zoster infection in secondary diagnoses age =18 years

Exclusion Criteria:

• Hospital discharge records for Herpes Zoster infection in primary diagnosis age <18 years

• Hospital discharge records for Herpes Zoster infection in secondary diagnoses age <18 years

Related Conditions & MeSH terms

• Comorbidities and Coexisting Conditions
• Herpes Simplex
• Herpes Zoster

Intervention

Other:
• Hospitalization
Population of patients hospitalized for Herpes Zoster (ICD9-CM 053.xx)

Locations

Country	Name	City	State
Italy	University of L'Aquila	L'Aquila

Sponsors (2)

Lead Sponsor	Collaborator
University of L'Aquila	GlaxoSmithKline

Country where clinical trial is conducted

Italy, 

References & Publications (19)

Calabro GE, Tognetto A, Carini E, Mancinelli S, Sarnari L, Colamesta V, Ricciardi W, de Waure C. Strategies to Improve Vaccination among At-Risk Adults and the Elderly in Italy. Vaccines (Basel). 2020 Jul 4;8(3):358. doi: 10.3390/vaccines8030358. — View Citation

Di Legami V, Gianino MM, Ciofi degli Atti M, Massari M, Migliardi A, Tomba GS, Zotti C; Zoster Study Group. Epidemiology and costs of herpes zoster: background data to estimate the impact of vaccination. Vaccine. 2007 Oct 23;25(43):7598-604. doi: 10.1016/j.vaccine.2007.07.049. Epub 2007 Aug 15. — View Citation

Diez-Domingo J, Weinke T, Garcia de Lomas J, Meyer CU, Bertrand I, Eymin C, Thomas S, Sadorge C. Comparison of intramuscular and subcutaneous administration of a herpes zoster live-attenuated vaccine in adults aged >/=50 years: a randomised non-inferiority clinical trial. Vaccine. 2015 Feb 4;33(6):789-95. doi: 10.1016/j.vaccine.2014.12.024. Epub 2014 Dec 30. — View Citation

Esteban-Vasallo MD, Dominguez-Berjon MF, Gil-Prieto R, Astray-Mochales J, Gil de Miguel A. Sociodemographic characteristics and chronic medical conditions as risk factors for herpes zoster: a population-based study from primary care in Madrid (Spain). Hum Vaccin Immunother. 2014;10(6):1650-60. doi: 10.4161/hv.28620. Epub 2014 May 7. — View Citation

Fiasca F, Necozione S, Fabiani L, Mastrodomenico M, Mattei A. Measles-Related Hospitalizations in Italy, 2004-2016: The Importance of High Vaccination Coverage. Ann Glob Health. 2019 Mar 19;85(1):40. doi: 10.5334/aogh.2455. — View Citation

Gabutti G, Franco E, Bonanni P, Conversano M, Ferro A, Lazzari M, Maggi S, Rossi A, Scotti S, Vitale F, Volpi A, Greco D. Reducing the burden of Herpes Zoster in Italy. Hum Vaccin Immunother. 2015;11(1):101-7. doi: 10.4161/hv.34363. Epub 2014 Nov 1. — View Citation

Gabutti G, Serenelli C, Cavallaro A, Ragni P. Herpes zoster associated hospital admissions in Italy: review of the hospital discharge forms. Int J Environ Res Public Health. 2009 Sep;6(9):2344-53. doi: 10.3390/ijerph6092344. Epub 2009 Sep 2. — View Citation

Gialloreti LE, Merito M, Pezzotti P, Naldi L, Gatti A, Beillat M, Serradell L, di Marzo R, Volpi A. Epidemiology and economic burden of herpes zoster and post-herpetic neuralgia in Italy: a retrospective, population-based study. BMC Infect Dis. 2010 Aug 3;10:230. doi: 10.1186/1471-2334-10-230. — View Citation

Grose C. Varicella vaccination of children in the United States: assessment after the first decade 1995-2005. J Clin Virol. 2005 Jun;33(2):89-95; discussion 96-8. doi: 10.1016/j.jcv.2005.02.003. — View Citation

Humphries KH, Rankin JM, Carere RG, Buller CE, Kiely FM, Spinelli JJ. Co-morbidity data in outcomes research: are clinical data derived from administrative databases a reliable alternative to chart review? J Clin Epidemiol. 2000 Apr;53(4):343-9. doi: 10.1016/s0895-4356(99)00188-2. — View Citation

Kim YJ, Lee CN, Lee MS, Lee JH, Lee JY, Han K, Park YM. Recurrence Rate of Herpes Zoster and Its Risk Factors: a Population-based Cohort Study. J Korean Med Sci. 2018 Dec 20;34(2):e1. doi: 10.3346/jkms.2019.34.e1. eCollection 2019 Jan 14. — View Citation

Koshy E, Mengting L, Kumar H, Jianbo W. Epidemiology, treatment and prevention of herpes zoster: A comprehensive review. Indian J Dermatol Venereol Leprol. 2018 May-Jun;84(3):251-262. doi: 10.4103/ijdvl.IJDVL_1021_16. — View Citation

Nardone A, de Ory F, Carton M, Cohen D, van Damme P, Davidkin I, Rota MC, de Melker H, Mossong J, Slacikova M, Tischer A, Andrews N, Berbers G, Gabutti G, Gay N, Jones L, Jokinen S, Kafatos G, de Aragon MV, Schneider F, Smetana Z, Vargova B, Vranckx R, Miller E. The comparative sero-epidemiology of varicella zoster virus in 11 countries in the European region. Vaccine. 2007 Nov 7;25(45):7866-72. doi: 10.1016/j.vaccine.2007.07.036. Epub 2007 Aug 8. — View Citation

Nimmo A, Steenkamp R, Ravanan R, Taylor D. Do routine hospital data accurately record comorbidity in advanced kidney disease populations? A record linkage cohort study. BMC Nephrol. 2021 Mar 17;22(1):95. doi: 10.1186/s12882-021-02301-5. — View Citation

Pinchinat S, Cebrian-Cuenca AM, Bricout H, Johnson RW. Similar herpes zoster incidence across Europe: results from a systematic literature review. BMC Infect Dis. 2013 Apr 10;13:170. doi: 10.1186/1471-2334-13-170. — View Citation

Stein AN, Britt H, Harrison C, Conway EL, Cunningham A, Macintyre CR. Herpes zoster burden of illness and health care resource utilisation in the Australian population aged 50 years and older. Vaccine. 2009 Jan 22;27(4):520-9. doi: 10.1016/j.vaccine.2008.11.012. Epub 2008 Nov 21. — View Citation

Tartari F, Spadotto A, Zengarini C, Zanoni R, Guglielmo A, Adorno A, Valzania C, Pileri A. Herpes zoster in COVID-19-positive patients. Int J Dermatol. 2020 Aug;59(8):1028-1029. doi: 10.1111/ijd.15001. Epub 2020 Jun 12. No abstract available. — View Citation

Thomas SL, Hall AJ. What does epidemiology tell us about risk factors for herpes zoster? Lancet Infect Dis. 2004 Jan;4(1):26-33. doi: 10.1016/s1473-3099(03)00857-0. — View Citation

Valente N, Cocchio S, Stefanati A, Baldovin T, Martinelli D, Prato R, Baldo V, Gabutti G. Temporal trends in herpes zoster-related hospitalizations in Italy, 2001-2013: differences between regions that have or have not implemented varicella vaccination. Aging Clin Exp Res. 2017 Aug;29(4):771-779. doi: 10.1007/s40520-017-0782-z. Epub 2017 Jun 12. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Co-morbidities among Herpes Zoster hospitalizations	Rate of patients hospitalized for Herpes Zoster with co-morbidities	2011-2021
Secondary	Shingles annual hospitalization rates	Shingles annual hospitalization rates in the Italian adult population aged 18+	2011-2021
Secondary	Shingles hospitalization rates by age classes	Shingles hospitalization rates by age classes:18-30; 31-40; 41-50; >50	2011-2021
Secondary	Herpes Zoster and COVID-19 infection	Proportion of patients with HZ vs. patients with HZ and COVID-19 infection	2020-2021
Secondary	Risk factors associated to deaths, a longer length of stay in hospital or the presence of zoster-complications among Herpes Zoster-related hospitalizations in the entire Italian general adult population	Incidence Rate Ratio (IRR) of deaths, longer length of stay in hospital or presence of zoster-complications among Herpes Zoster-related hospitalizations in the entire Italian general adult population	2011-2021