Clinical Epidemiology And Prevention Of Herpes Zoster

Herpes zoster is a viral skin disease caused by the reactivation and replication of latent varicella-zoster virus (VZV), a cluster of blister with nerves distributed in a unilateral distribution. Pain is characteristic. Herpes zoster is self-limiting, but serious cases and complications reduce the quality of life of patients and increase the economic burden of patients’ families and society. It is important to understand the clinical epidemiological characteristics and prevention of herpes zoster. In recent years, a number of pooled analyses have summarized the clinical epidemiological characteristics of herpes zoster. The results are representative, but vary depending on the study data source or post-herpetic neuralgia (PHN) definition.

1. Clinical epidemiology of herpes zoster

1.1 Pathogens and transmission routes

1.1.1 Etiology

VZV belongs to the human herpesvirus alpha subfamily, also known as human herpesvirus type 3 (HHV-3), which is a double-stranded DNA virus with neurotropic and dermal properties, and human beings are the sole host. VZV is divided into seven clades of 1, 2, 3, 4, 5, VI and VII, but only one serotype. The lipid envelope of VZV is easily degraded by organic solvents, detergents or proteases to render the virus infective. The virus has weak resistance in vitro, is not heat-resistant and is not resistant to acid, and can be inactivated by diethyl ether. When VZV is infected, it enters the local lymph node through the respiratory mucosal epithelium. The infected lymphocytes then enter the blood circulation and infect the peripheral blood mononuclear leukocytes through the lymphatic circulation. The virus spreads to the skin with blood flow, and the clinical manifestation is chickenpox. After the chickenpox has healed, the virus lurks in the brain ganglia, the spinal dorsal root ganglia, autonomic neurons or intestinal neurons. When the body’s resistance is reduced, the latent virus is reactivated, replicated, and migrated along the peripheral nerve to the skin, clinically showing herpes zoster.

1.1.2 Route of transmission

VZV is highly contagious, and patients with chickenpox or herpes zoster are the only source of infection, mainly transmitted by droplet air and/or direct contact. Patients with chickenpox receive the virus by saliva or eye fluid 2 days before the onset of rash. The blister fluid of patients with varicella or herpes zoster contains infectious virus particles, which can be inhaled by susceptible persons after being atomized or drifted. It can also be directly contacted with skin lesions, and the more the lesions are, the more contagious. Chickenpox can occur after infection, but it does not directly cause herpes zoster.

1.1.3 Susceptible person

95% to 97% of women of childbearing age are positive for serum anti-VZV antibodies. Therefore, it is easy for pregnant women born to serum antibody-negative adults, pregnant women with negative serum antibodies, immunodeficiency, pregnant women who have had chickenpox in the 4th to 5th months of pregnancy, and newborns born to mothers who have had chickenpox before and after childbirth. A serious VZV primary infection has occurred. Older people, immunodeficiency, mothers who have had chickenpox during pregnancy, and children who have had chickenpox for one year after birth have an increased risk of herpes zoster.

1.2 Clinical epidemiology

1. 2. 1 Incidence rate

North America and Europe > 95% of young people are positive for serum VZV antibodies and are at risk for herpes zoster. Based on the population base, the incidence of herpes zoster is (3 to 5) / (1000 person-years), of which (3 to 10) / (1000 person-years) in Asia-Pacific and 10. 4/(thousands in Korea) People, year, Japan is 10. 9/ (thousands of people), and China’s mainland and Taiwan are (3.4 ~ 5. 8) / ( thousand people · years) and ( 4. 89 ~ 5. 67 ) / (Thousands of people). There is currently no data on the incidence of herpes zoster in Africa. However, in tropical Africa, the prevalence of VZV infection in high-income populations and high HIV infection rates may increase the incidence of varicella, and the aging of the population, the prevalence of diabetes and the high rate of HIV infection may make herpes zoster. Increasing morbidity and overwhelming medical systems can also increase the incidence of complications of varicella and herpes zoster.

1. 2. 2 Hospitalization rate, recurrence rate and mortality rate

The hospitalization rate of herpes zoster has been reported to be quite different in the literature. Based on the population base, the hospitalization rate for herpes zoster (2 to 25) / (100,000 person-years). The hospitalization rate is 3% to 4% in the case of the herpes zoster patient base, and 4.5% to 9.1% and 2.93% in China’s mainland and Taiwan, respectively. The recurrence rate of herpes zoster is 1% to 6%, but the difference reported in the literature is large, ranging from an 8-year recurrence rate of 6.2% to a lifetime recurrence rate of 3% to 5%. The recurrence of herpes zoster is associated with low patient immunity, with HIV infections reaching 13% to 26%. The mortality rate of herpes zoster is not much, but it is not high overall. According to the population base, the mortality rate of herpes zoster is (0. 017 ~ 0. 465) / (100,000 person-years), and the death is ≥ 60 years old disabled or with basic diseases. The total mortality rate of herpes zoster in European countries is (0 to 0.07)/100,000, and that of French-aged 95-year-olds is 19.48/100,000. The mortality rate of younger and older women is slightly higher. The case fatality of herpes zoster is 2/100,000 in patients aged 45-65 years and 61/100,000 in patients ≥65 years old. The hospital fatality of herpes zoster was 0.6% in the United Kingdom from 45 to 65 years old and 7. 1% in the Spanish patients aged ≥80 years.

1. 2. 3 Complications or sequelae

About 13% to 47% of patients with herpes zoster have complications or sequelae, mainly involving the nervous system and the eye. Nervous system complications include post-herpetic neuralgia (PHN), Ramsay-Hunt syndrome, Bell facial paralysis, meningitis, myelitis, and transient cerebral ischemia or stroke. The main eye complication is herpes zoster ophthalmicus (HZO).
PHN is the most common sequela of herpes zoster, but the definition of PHN is still controversial. Some domestic scholars have defined PHN as the pain after the rash has subsided for more than 1 month. The internationally accepted definition is that the pain persists for more than 90 days after the rash appears. About 30% to 50% of PHNs last for more than 1 year, and a few can last up to 10 years. According to the internationally accepted definition of PHN, the incidence of PHN in patients with herpes zoster is about 5% to 30%, most of the reports are 10% to 20%, and in China, 8.6% to 13.8%. The incidence of PHN increases with the age of the patient, about 8% for patients ≥50 years old and 33% for patients ≥80 years old. It has also been reported that the incidence of PHN in women is higher than in men. PHN risk factors are relatively clear, advanced age, severe prodromal symptoms, heavy rash, severe pain and low immunity. Trigeminal involvement, as well as SLE, diabetes or neuropsychiatric disorders are also susceptible to PHN. HZO is caused by the latent VZV being reactivated and replicated after the trigeminal nerve branch. Based on the population base, the incidence of HZO was 30.9/100,000, and the number of people aged ≥65 years was 10.46/100,000. According to the base of patients with herpes zoster, the incidence of HZO is 10% to 20%, which also increases with age. The clinical manifestations of HZO were blepharitis, keratitis, conjunctivitis, scleritis, uveitis or acute progressive retinal necrosis. About 5% of HZO patients in the United States have eye damage, of which 6% are blind. About half of HZO patients have skin damage, and about 21% eventually develop into PHN. Older or immunocompromised patients may also have recurrent episodes of herpes zoster, disseminated lesions or associated with bacterial infections or sputum hyperplasia, and may also cause viral resistance. Severe cases even involve many organs such as the lungs, gastrointestinal tract, and brain. Hepatitis, pancreatitis, pneumonia, myocarditis, esophagitis, or digestive ulcers occur before the appearance of herpes zoster rash, which is easily misdiagnosed.

1. 2. 4 Disease burden

The painful symptoms of herpes zoster affect the daily activities and sleep of the patient. The more severe the pain, the greater the quality of life of the patient. PHN pain also causes negative psychological burden on the patient, with approximately 29% of herpes zoster and 43% of PHN with moderate anxiety or depressive symptoms. Herpes zoster and its complications aggravate the medical burden of the patient, family and society, but the medical burden varies from country to country due to different levels of economic development. It is estimated that the per capita medical expenses for herpes zoster in mainland China is 840 yuan. The year of illness, the region, and the presence or absence of hospitalization or sequelae affect the medical expenses. The medical expenses for shingles in Taiwan in 2000 were about NT$250 million, up to 320 million in 2004, an increase of 1.22 times.

1. 3 Risk factors

1. 3. 1 Age

Old age is the most important risk factor. With age, the body’s T cell-mediated cellular immunity (TCMI) against VZV is gradually decreasing, and the incidence of herpes zoster is increased. The lifetime risk is about 30%, but it rises sharply after 50 years, at >85 years old. The crowd is up to 50%. Kawai et al. found that the incidence of herpes zoster in the age of 60 years (6-8) / (1000 person-years), >80 years old population (8-12) / (1000 person-years). The incidence of herpes zoster in the population aged ≥ 80 years in China is 3. 21 times that of people aged ≥ 50 years old, and those in Taiwan 40 to 50, 50 to 60, 60 to 70 and > 70 years old are 5. 18, 8. 36, respectively. 11. 09 and 11.77/( thousand people·year). In addition, hospitalization, mortality, and hospital mortality for herpes zoster also increase with age.

1. 3. 2 Gender

Women are important predisposing factors. A summary analysis by Yawn et al found that the incidence of herpes zoster in women and men was 3. 9/(thousands per year) and 3. 2/( thousand people per year). In the Asia-Pacific region, the incidence rates of women and men in Korea are 12. 6 / ( thousand people · year) and 8. 3 / ( thousand people · year), respectively, Japanese women and men are 12. 8 / ( thousand people · year And 8.5/( thousand people·years), the incidence of women in mainland China and Taiwan is also higher than that of men.

1. 3. 3 Low immunity

Low immunity is another important risk factor. American herpes zoster patients 6. 6% to 8. 0% are immunocompromised. Receiving organ or hematopoietic stem cell transplantation, receiving immunosuppressive therapy, with malignant tumors such as lymphoma or leukemia, combined with chronic diseases such as diabetes, SLE or depression, HIV infection, etc., leading to impaired T cell immune function, herpes zoster and severe concurrency The risk of the disease is therefore increased. The incidence of herpes zoster in elderly patients with cancer is 1.2 to 2.4 times that of non-tumor population, and that of patients with hematologic malignancies is as high as 31/(1000 person-years). The incidence of herpes zoster in HIV-infected patients is higher ( 29. 4 ~ 51.5) / (1000 person-years), 10 to 30 times that of non-HIV-infected patients, and the symptoms are severe, the course is long and the central nervous system is easily involved. System or eye. In areas where HIV is endemic, young people with herpes zoster are even considered one of the signs of HIV infection. Despite the decline in the incidence of herpes zoster after antiretroviral treatment in HIV-infected patients, it is still higher than the general population.

1. 3. 4 Geographical distribution and seasonal changes

Whether the geographical distribution affects the clinical epidemiology of herpes zoster is still controversial. Zhu et al reported that the incidence of herpes zoster in the Pearl River Delta region of Guangdong Province is higher than that in the north. Li et al reported that the incidence of herpes zoster in urban population in China is higher than that in rural areas, but WHO believes that there is no regional difference in the incidence of herpes zoster. Whether seasonal changes affect the clinical epidemiology of herpes zoster is also controversial. The prevalence of varicella and herpes zoster is mirrored. The chickenpox occurs in winter and spring and herpes zoster occurs in summer and autumn. Herpes zoster may be associated with decreased UV-induced cellular immune function in summer and autumn, but other The results of the study were not supported.

2. Clinical epidemiological factors

2. 1 Varicella vaccine

The human body naturally infects VZV and stimulates the production of virus-specific antibodies and T-CMI, which play an important role in protecting varicella and herpes zoster and promoting disease recovery. Currently, a live attenuated varicella vaccine (vOka) prepared with the varicella virus Oka strain has been included in the routine vaccination program for children in most countries. After inoculation with a single dose of varicella vaccine, the incidence of varicella and moderate to severe varicella was reduced by 81% and 98%, respectively, and the two doses were reduced by 92% and 100%, respectively. The impact of vaccination against varicella vaccine on the clinical epidemiology of herpes zoster is still controversial. Tanuseputro et al. observed that the outpatient visit rate and hospitalization rate of varicella after vaccination against varicella decreased by 9% and 53%, respectively, and the incidence of herpes zoster in children under 9 also decreased by 29%. However, Chao et al reported that with the increase in the number of varicella vaccination, the incidence of varicella decreased by 75% to 80%, while the incidence of herpes zoster increased. Wu et al reported that the incidence of varicella in Taiwan from 2000 to 2009 decreased from 7.14/(1000 person-years) to 0.76/(thousands-year), and the incidence of herpes zoster was from 4.04/(thousands). The number of people/years rose to 6.24/(thousands of years), and the incidence of varicella and herpes zoster was negatively correlated before and after vaccination against varicella. Most observations have shown that the incidence of herpes zoster gradually increases with time, regardless of whether or not the varicella vaccine is vaccinated. For example, the incidence of herpes zoster in the Olmsted County of the United States increased by 28% between 1996 and 2001, with an average annual increase of 5.6%. Kawai et al. observed that the incidence of herpes zoster in Omstead County increased by 4 times between 1945 and 2007, with an average annual rate of 2.5%. Chen et al also observed an average annual increase in the incidence of herpes zoster in the Asia-Pacific region of about 5%. There is no consensus on how to explain the increasing trend of the incidence of herpes zoster. After the human body naturally infects VZV, the body enhances the immunity against the virus through exogenous “immune enhancement”, thereby reducing the incidence of herpes zoster. Vaccination against varicella vaccine by weakening this

Exogenous “immunity enhancement” increases the incidence of herpes zoster. In addition, the live virus contained in the varicella vaccine may be lurking in the ganglion. When the body’s resistance is reduced, the latent virus can be reactivated and replicated to cause herpes zoster, but the live virus of the varicella vaccine is low, and the vaccine virus is on the pathogenesis of herpes zoster. The rate impact is minimal. The researchers therefore believe that the gradual increase in the incidence of herpes zoster cannot be attributed solely or directly to the varicella vaccine, nor can it be attributed solely to advanced age or reduced resistance. Some researchers have established a simulation model to evaluate the impact of vaccination against varicella vaccine. It is believed that vaccination against varicella in a short period of time may increase the incidence of herpes zoster by attenuating exogenous “immune enhancement”.
But long-term (such as 50 years) may reduce the incidence.

2. 2 Other factors

The data on the clinical epidemiology of herpes zoster is mostly derived from the health care system, the primary care system, the medical insurance system or the inpatient system database. Therefore, the degree of database perfection also affects the epidemiology of herpes zoster. The health care or primary care system only provides patient data, the health insurance system only reflects the information of the insured, and the inpatient system provides only inpatient information. In addition, the level of economic development and health status may also affect the clinical epidemiology of herpes zoster. In Africa, an inadequate medical treatment system may increase the incidence and mortality of herpes zoster.

3. Prevention of herpes zoster

3. 1 General measures

The risk of herpes zoster in adults after the age of 50 has risen sharply. Therefore, improving the resistance of this group is the primary preventive measure. Promote a healthy lifestyle, maintain a happy mood, regular work and diet, diet, moderate physical exercise, and actively treat patients with basic diseases. Because vesicular fluids in patients with herpes zoster contain infectious viruses, contact isolation measures should be taken to prevent contact with the infected person. For patients with disseminated herpes zoster with low immunity, respiratory tract isolation should be taken until the lesions are detached.

3. 2 Herpes zoster vaccine

The virus-specific T-CMI induced by VZV in the body naturally declines with age. For example, virus-specific CD4 cells from 60 to 69 years old produce IFNγ, IL-4 and IL-5, which are lower than younger 5 The CD4 early effector cells and CD8 effector memory cells were lower. Although asymptomatic activation or reinfection of VZV maintains T-CMI to some extent, it is not sufficient to prevent herpes zoster. Therefore, stimulating the body’s virus-specific T-CMI by vaccination is the key to preventing herpes zoster. The only live attenuated herpes zoster vaccine Zostavax and the live attenuated varicella vaccine were prepared in the market by vOka strain, but their virus titer and antigen content were 14 times and 10 times higher than those of varicella vaccine, respectively. Zostavax prevents herpes zoster by stimulating the body’s virus-specific T-CMI, such as the induction of high-level cytokines (IFN-γ, IL-2 and TNF-α) by multi-functional CD + 4 and CD + 8 T cells. Immune response of IE63, IE62, gB, ORF9 and gE. At present, more than 60 countries and regions such as the European Union and the United States have recommended Zostavax® to prevent herpes zoster and PHN in people with normal immune function of ≥50 years old. The vaccination method was a subcutaneous injection of a single dose of vaccine (0.55 mL, containing 19,400 PFU virus) in the upper arm deltoid area. Occasionally, there are adverse reactions such as headache and injection of local reactions. After a large-scale multi-center clinical trial, the incidence of herpes zoster after vaccination was reduced by 69.8% in people with normal immune function between 50 and 59 years old, and the incidence of herpes zoster, PHN incidence and disease burden after vaccination in ≥60 years old, respectively. The decline was 51.3%, 66.5% and 61.1%. However, the preventive efficiency of Zostavax gradually decreases with the age of the vaccinator, and severe immunosuppression and pregnant women are contraindications for vaccination. Therefore, the need to prepare safer and more effective vaccines is particularly urgent. 2% and 91.2%, respectively, the herpes zoster subunit vaccine (HZ/su) prepared by VZV gE recombinant protein and AS01B adjuvant, the incidence of herpes zoster and PHN decreased by vaccination of ≥ 50 years old. The population vaccinated by ≥70 years old was reduced by 89.8% and 88.8% respectively, which is better than live attenuated vaccine, and the application prospect may be better.

3. 3 Other

It has been reported that HIV-infected patients with low-dose acyclovir prophylaxis can reduce the incidence of herpes zoster.

4. Conclusion

According to the population base, the incidence of herpes zoster is (3 to 5) / (1000 person-years) and increases by 2.5% to 5% year-on-year. The hospitalization rate is (2 to 25) / (100,000 people per year) The mortality rate is (0. 017 ~ 0. 465) / (100,000 people a year). The recurrence rate of herpes zoster is 1% to 6%. The predisposing factors include advanced age, female and low immunity. The main complications are PHN and HZO. Patients with advanced age, severe prodromal symptoms, severe rash, severe pain, or low immunity are more likely to develop PHN. Herpes zoster and PHN reduce the quality of life of patients and increase the financial burden on their families and society. Improving the body’s resistance is the primary preventive measure, and live attenuated herpes zoster vaccine can effectively prevent herpes zoster and PHN.