Annisa L, et al.
Current topics in human varicella.
Current topics in human varicella infection: Pearls and Luthvia Annisa1*.
Mohamad S.
Hakim2.
Abu T.
Aman1 Department of Microbiology.
Faculty of Medicine.
Public Health, and Nursing.
Universitas Gadjah Mada.
Yogyakarta.
Indonesia, 2Postgraduate School of Molecular Medicine.
Erasmus MCUniversity Medical Center.
Rotterdam, the Netherlands https://doi.
org/10.
22146/inajbcs.
ABSTRACT
Submitted: 2023-08-02 Accepted : 2024-02-29 Varicella zoster virus (VZV), an alphaherpesvirus, is a highly contagious and neurotropic virus infecting the majority of the adult and pediatric population Varicella zoster virus is the only human herpesvirus for which a licensed live attenuated vaccine has been developed.
It can be considered that additional study on VZV is superfluous given the significant success of the VZV vaccines.
This has been the case for other viruses including rubella and measles, for which effective vaccinations are widely available.
Contrarily, much regarding VZV, a complex and chronic human disease due to its latency, still needs to be uncovered.
Over the past two decades, our understanding of the molecular biology of VZV and its pathogenicity has expanded.
In this review, we discussed our recent understanding of VZV biology, pathogenesis as well as its clinical aspect, including diagnosis, clinical management, and vaccine development.
ABSTRAK
Keywords:
clinical manifestation.
varicella zoster virus Virus varicella zoster (Varicella zoster virus/VZV), salah satu anggota alphaherpesvirus, merupakan virus neurotropik dan sangat mudah Sebagian besar populasi anak-anak dan dewasa di seluruh dunia telah terinfeksi virus ini.
Virus varicella zoster adalah satu-satunya anggota famili herpesviridae yang dapat dicegah dengan pemberian vaksin.
Karena keberhasilan vaksin terhadap pencegahan infeksi VZV, muncul asumsi bahwa penelitian lebih lanjut terhadap VZV menjadi tidak diperlukan lagi.
Hal yang sama terjadi virus lain yang telah memiliki vaksin yang efektif, seperti virus campak dan rubela.
Padahal fakta menunjukkan sebaliknya, masih banyak yang harus kita teliti terkait VZV.
Karena kemampuannya dalam berkembang menjadi infeksi laten, infeksi VZV menjadi kompleks dan persisten dalam tubuh manusia.
Oleh karena itu, dalam dua dekade terahir, pengetahuan terhadap biologi molekuler dan patogenesis infeksi VZV berkembang dengan pesat.
Pada artikel ini, kami membahas pengetahuan terkini tentang aspek biologi dari VZV, patogenesis, dan juga aspek klinis, meliputi diagnosis, manajemen, dan pengembangan vaksin.
INTRODUCTION
Herpesviruses have been found in a large variety of vertebrates.
Naturally, associated with a single host species.
Indeed, several herpesviruses have been known to infect humans.
This host*corresponding author: luthvia.
annisa@ugm.
specific herpesvirus infection indicates that they are well adapted to their hosts over a long time.
Thus, herpesviruses have been recognized as a group of viruses with magnificent evolutionary The economic burden associated with VZV infection is substantially InaJBCS.
Volume 56.
Number 4, 2024 October: 361-376 2 Varicella zoster virus is highly It is a neurotropic virus infecting the majority of adult and Varicella zoster virus belongs to the Varicellovirus genus.
Clinically.
VZV infection manifests in two distinct forms:
primary infection with a widespread vesicular skin rash .
hickenpox or varicell.
and reactivation of latent infection with a particular dermatomal skin rash .
hingles or herpes zoster (HZ)].
Following the primary infection .
VZV establishes a long-term stage of infection .
in the sensory ganglia, and in a specific condition.
VZV can be reactivated.
4 The incidence of HZ increases with age or in various immunosuppressed conditions.
Many animal models of VZV infection have been developed.
Seroconversion without clinical signs has been observed following experimental VZV inoculations in mice and guinea pigs.
6 On the other hand, infection with the closely related simian varicella virus (SVV) in nonhuman primates (NHP) resulted in 7 Despite being laborious and expensive, the NHP model has offered vital insights into the neurotropism and pathophysiology of varicella that are not possible with any other models.
8 During the past two decades, understanding of the molecular biology of VZV and its pathogenicity has markedly increased.
In this review, we discussed current developments in the knowledge of both the biological and clinical aspects of human varicella infections, as well as highlight aspects as to why VZV is a complex pathogen to humans.
MATERIALS AND METHODS
databases: MEDLINE and Google Scholar for human varicella infections, using the Boolean search string of AoVaricella OR human varicella OR varicella zoster virus AND .
pidemiology OR diagnostic OR management OR complications OR After removing duplicates, a total of 61 articles were used and synthesized for a narrative review.
RESULTS AND DISCUSSION
Epidemiology of varicella Globally, varicella is considered endemic in many populations and whole-year with epidemics occurring every two to three years.
Five viral clades and their corresponding geographic distribution have been found by viral genomic studies: clades 1, 3, and 5 are European in origin.
clade 2 comprises Asian strains, including the parental Oka strain from which varicella vaccine was developed.
and clade 4 comprises African strains.
9,10 In India, several outbreaks were reported between 20152020, but the majority occurred in tribal mountainous areas.
11 In Indonesia, the exact number of prevalence could not be found.
There is only one study reporting the seroprevalence of varicella zoster antibodies to be two-thirds of the population at the age of 15 y.
, but this study was conducted over 20 yr ago.
In temperate regions, the incidence of varicella is most common in preschool-aged and early elementary school children, with an annual incidence of over 100 per 1,000 children.
In tropical regions, the mean age of contracting varicella is older, with a higher proportion of cases occurring in The differences may be caused by the virusAos characteristics, such as its inactivation by heat and/or humidity, or variables that influence the risk of 9,13 There is a noticeable seasonal trend to varicella, with peak incidence occurring Annisa L, et al.
Current topics in human varicella.
in the winter and spring or the cool, dry 13 Typically, outbreaks occur in places where children congregate, such as daycares and schools, although they can also happen in other age groups.
Recently, in the Bantul district.
Special Region of Yogyakarta.
Indonesia, an outbreak of varicella was reported in an elementary school affecting eighteen students and is confirmed to have originated from one student, illustrating varicellaAos high reproduction number.
The epidemiology of varicella has undergone significant changes in nations where childhood immunization against the disease is recommended.
Within the United States (US) where it has universal varicella vaccination, hospitalizations, and deaths have decreased by almost 95% since the programAos introduction in 1995, concluding a herd immunity achieved, and in addition to that, a stoppage of yearly outbreaks.
While the global epidemiology study is well documented for varicella, the same cannot be said about zosters, where the majority of epidemiology studies were reported from developed countries only.
The incidence of zosters is higher nowadays than it was decades ago, but it is mainly due to the advances in medicine that result in the growing of the elderly population above anything 9,17,18 The biology of VZV and its pathogenesis The structure of virion particle The diameter of the VZV particle .
is O150-200 nm.
The virion is composed of three concentric layers (FIGURE .
19 The innermost layer is an icosahedral nucleocapsid core containing the VZV genome.
The capsid is composed of several proteins that are encoded by orf20, orf21, and orf23 genes, among others.
The second .
layer is a tegument, consisting of various viraland host-derived proteins surrounding the nucleocapsid.
Its precise structure is less understood, yet mainly consists of regulatory proteins, such as the intermediate-early (IE) protein that functions as viral transactivating It is also composed of viral proteins with unknown functions.
The outermost layer is a lipid-rich envelope composed of a host-derived lipid bilayer .
ipid membran.
with inserted viral glycoproteins, including glycoprotein B .
B)/gH-gL, which form the minimal .
fusion complex.
FIGURE 1.
Schematic representation of the VZV particle .
InaJBCS.
Volume 56.
Number 4, 2024 October: 361-376 The genome of VZV Varicella zoster virus has a linear double-strand DNA genome, about 125 kbp in length.
Its G C content is about However, the VZV genome can undergo circularization mediated by unpaired bases at each end.
The genome encodes at least 71 unique open reading frames (ORF.
The majority of VZV genes .
bout two-third.
are essential for viral replication, as shown in various in vitro studies.
Most of them belong to the 40 well-characterized genes that are present in all herpesviruses.
20 The genome consists of a unique long (UL) of 105,000 bp and a unique short (US) region of 5,232 bp.
Additionally, the genome contains internal (IR) and terminal repeat (TR) regions.
VZV entry into target cells Similar to other viruses, the life cycle of VZV begins with the entry of the virion.
Currently, this entry process remains poorly understood.
Presumably, it goes via either endocytosis or direct fusion of viral particles with the plasma The surface glycoproteins, including gB, gH, and gL, play a pivotal role as the core fusion complex.
They are suggested to interact with cell surface molecules, including myelin-associated glycoprotein or mannose-8-phosphate 19 Following entry into a specific target cell, the tegument protein is subsequently released.
This release leads to an alteration of the intracellular environment of the infected hosts, thereby inhibiting antiviral responses and importantly, influencing the outcome of the virus life cycle, i.
, lytic or latent VZV replication within the target cells The nucleocapsid core goes through primary envelopment, packages newly generated genomic DNA, moves to the inner nuclear membrane, and buds across the nuclear membrane.
The nucleocapsid thus experiences deenvelopment during translocation to the cytoplasm.
The nucleocapsid enters the cytoplasm, followed by a secondary envelopment in the cisternae of the transGolgi network (TGN).
The nucleocapsid by acquiring viral glycoproteins .
hat mature in the trans-Golgi regio.
and the tegument proteins .
hat assemble in Nascent viral particles are then transported out to the cell surfaces, via post-Golgi compartment vesicles, where the freshly assembled virus particles are finally released (FIGURE .
The first enveloped progeny of virions is identified nine hours following primary infection.
Within twelve hours of infection, numerous virions are found on the cell surfaces.
The assembled virions of VZV often maintain a highly cell-associated state, which makes it distinct from other viruses.
The same viral glycoproteins thought to facilitate the entrance process are produced on the cell membranes and facilitate the fusion of the infected and uninfected cells.
This process results in the formation polykaryocytes, which furthers the virusAos ability to disseminate throughout the body.
19,20
Annisa L, et al.
Current topics in human varicella.
FIGURE 2.
VZV life cycle .
within the infected cells.
Transmission of VZV Varicella zoster virus is a virus that spreads easily and mostly does so in two ways: .
by coming into close proximity with skin lesions that havenAot completely healed and crusted .
ontact or .
by inhaling viral aerosols from vesicular skin lesions .
irborne transmissio.
21,22 The period of communicability lasts from one to two days prior to the appearance of the rash until all lesions have crusted.
23 Indeed, in the period of 24 to 48 hr before the first skin eruption, the infected host is highly contagious and spreads the virus through the respiratory route.
23,24 Skin lesions from varicella and zoster both have a lot of infectious viruses in them, which is how they spread to those who are vulnerable.
While viral transmission from people with HZ may occur and can result in the development of primary individuals.
HZ is considered to be less infectious than varicella.
Pathophysiology manifestations of VZV infection Primary VZV infection Varicella zoster virus enters the host mainly through the upper respiratory tract but sometimes conjunctiva is also The epithelial cells of the upper respiratory tract mucosa are the first and the main site of viral replication in primary VZV infection.
26,27 Those patients primarily contracted with VZV may experience prodromal symptoms before the development of classic vesicular rash.
28 Subsequently, the virus is disseminated to the tonsils and other local lymphoid tissues.
This process contributes to the bloodstream spread of the virus and is mediated by the systemic circulation of the infected T cells to the 29,30 A widely distributed vesicular rash develops after an incubation period of about 10 to 21 d.
However, the host is highly contagious and can transmit VZV via the respiratory route even 24 to 48 InaJBCS.
Volume 56.
Number 4, 2024 October: 361-376 hr before the initial skin eruption.
These rashes are mainly present on the trunk, head, and face (FIGURE 3 and .
24,31,32
Over a few days, the skin lesions commonly progress from papules to vesicles, and then to crusts.
The lesions can be found anywhere from a few to several hundreds of vesicles, with approximately 500 lesions.
In severe cases, more severe rashes are usually observed and thus, take a more prolonged time to completely heal.
Concomitant symptoms experienced by the patients include fever, malaise, and fatigue.
The symptoms frequently last about one
24,32
In addition to the discomfort of the primary skin eruption, primary VZV infection can result in severe consequences that increase morbidity These include superinfections of bacteria that may lead to necrotizing fasciitis, ataxia, and Guillain-Barre syndrome (GBS), as well as pneumonitis and even 24,33-35 In a high-risk population group, the clinical symptoms of primary VZV infection might be more severe.
Pregnant women, newborns, those who have never been vaccinated or exposed to an infection before, older adolescents, and those with compromised cellular immunity are among the high-risk After being vaccinated, a person may still get the illness when exposed to the virus.
Vaccine recipients who still get varicella infection typically experience milder illnesses with fewer vesicles and side effects compared to the natural The name Aubreakthrough varicellaAy refers to this condition, which is less communicable than primary 36 A one-dose vaccine recipient is far more likely to disseminate the virus to exposed varicella-susceptible individuals than a two-dose vaccine When a person catches varicella despite receiving two doses of the immunization, the disease is typically extremely mild and may be difficult to recognize as varicella, both in terms of clinical manifestation or by the laboratory profile.
31,37
Establishment of latent infection and After the primary infection resolves.
VZV enters the nerve ending and by retrograde axonal transport to the sensory nerve ganglia in the dorsal root ganglion where it stays dormant, this marks the state of VZV latent infection which can happen for decades until it is reactivated.
Herpes zoster, which is characterized by a vesicular rash in the dermatome, innervated by the afflicted ganglion, is caused by VZV accessing the skin during reactivation via anterograde axonal transport (FIGURE 3 and .
HZ, often referred to as AuzosterAy, is the illness that results from the symptomatic reactivation of VZV.
The typical manifestation of zoster is the emergence of a unilateral, dermatomal skin rash that is painful and/or itchy.
However, it is currently known that zoster may also occur without a rash.
Annisa L, et al.
Current topics in human varicella.
FIGURE 3.
Illustration on how VZV causes varicella .
rimary infectio.
, establishes latency, and then undergoes reactivation.
VZV enters the host through the upper respiratory tract Local replication in regional lymph nodes followed by spread to tonsils that eventually gain access to T cells .
uring days 2 through .
Primary VZV infection or chickenpox Primary viremia .
etween days 4 and .
followed by further viral replication in liver and spleen Secondary viremia seeds the whole body with virions that invade capillaries and able to spread to epidermis by days 14 through 16, leading to skin rashes VZV enters the nerve endings then transport to sensory nerve of dorsal root ganglia and stays dormant Latency Reactivation leads to infections of nerves and dermatomes Herpes zoster or Possible sequalae FIGURE 4.
Schematic diagram showing the pathophysiology of human VZV infection.
31,32
InaJBCS.
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Number 4, 2024 October: 361-376 Development of HZ is associated with the waning of cellular mediated immunity (CMI) against VZV infection.
VZV-specific CMI is essential for suppressing the onset of HZ.
38 This phenomenon is also observed in organ transplant recipients and people HIV/AIDS.
39,40
However, exact mechanism of viral reactivation following the decrease of the host CMI as well as the role of the humoral immunity remain unclear and thus need further 8,38 Several findings indicate that contact with varicella patients enhances immunity to VZV and the risk of developing HZ.
The zoster incubation period is unknown since the process of reactivation is not well understood.
unilateral vesicular rash on the trunk in one or two adjacent dermatomes is a defining feature of the zoster Despite it can also occur on the face, head, or extremities, it usually does not cross the bodyAos midline.
Although zoster is approximately half as transmissible as varicella, the vesicles are still packed with infectious virions that can spread through the air and infect surrounding varicella-susceptible individuals and cause chickenpox.
21,25
The zoster eruptions may be mild to moderate and resolve quickly, or it can be in a more severe form with larger lesions that may linger for several weeks, and in some cases, a painful complication known as post-herpetic neuralgia (PHN) may develop.
Elderly patients and immunocompromised individuals are more prone to experience this Several problems are linked to VZV reactivation, as follows: VZV vasculopathy.
Giant cell arteritis, segmental weakness and myelopathy.
VZV encephalitis.
VZV cranial neuropathies.
GBS, and zoster sine herpete (ZSH).
It is a specific term used when typical dermatomal discomfort associated with VZV develops without the associated rash.
Diagnosis of VZV infection The most frequent method of diagnosis for varicella and zoster is through clinical examination.
When a broad or isolated dermatomal vesicular skin rash manifests, the clinical diagnosis of VZV infection has often been made.
The diagnosis can be established by isolation of VZV DNA in the skin lesions by polymerase chain reaction (PCR) in rare instances .
uch as atypical rashes or rashes probably caused by other causes, including poxviruses, rickettsia, or contact dermatiti.
It is also possible to use a culture of VZV from skin lesions, although this method is more costly, takes longer, is less accessible, and is less sensitive than PCR.
Viral DNA may be found in cerebrospinal fluid (CSF) and/ or saliva in individuals with suspected encephalitis, meningitis, and other VZVrelated disorders.
Although reliable.
VZV-specific antibody measurements in blood samples do not provide quick enough data for clinical application due to the time needed for patients to produce antibodies.
31,32
Submission of clinical samples Skin .
ubmitted swabs, fluid, or scab.
, saliva, tissue, bronchoalveolar lavages (BAL).
EDTA blood, amniotic fluids, and CSF are examples of clinical samples used for PCR diagnosis.
If neurological symptoms or signs are present.
CSF may also be The patientAos sample must be transported in its primary container together with an outer package made of adsorbing material and packaged in a transport box .
ardboard bo.
Shipping at room temperature is feasible.
is only advised if the samples will be used for viral isolation in cell culture.
Early, meticulous sample collection and Annisa L, et al.
Current topics in human varicella.
optimal laboratory transfer are crucial for fruitful viral isolation.
32,41,42 A case of neuroretinitis caused by the VZV was confirmed by PCR testing of the ocular fluid has been reported.
Viral detection Virus confirmative evidence that a patient has an acute VZV infection.
For the detection of viral genomes in vesicles, tissues.
CSF.
BAL.
EDTA blood, or amniotic fluids.
PCR is the method of choice.
44,45
The PCR is particularly significant for evaluating CSF in the event of suspected acute CNS infections as well as for detecting amniotic fluids in the prenatal diagnosis of varicella infection during 46,47 Only limited cell types, including human embryonic fibroblasts, allow for the isolation of VZV.
This process is lengthy, demanding, and lacks clinically applicable sensitivity.
It also calls for a high degree of laboratory experience.
Noteworthy, only vesicle fluids with a high viral load are appropriate for viral For effective isolation, samples must be carefully and promptly collected, and they must be transported in the best possible way.
Detection of antibodies The assessment of antibody status following varicella immunization in healthy children, adolescents, and adults is not required due to the high rates of However, for healthcare professionals and immunodeficient vaccination recipients, immunological Serological VZV diagnosis is important to identify susceptible persons who need active or passive immunoprophylaxis.
To assess the immunity status and for vaccine research, highly particular glycoprotein enzyme-linked immunosorbent assays (ELISA.
or the fluorescent antibody to membrane (FAMA) 48 The measurement of VZV IgG seroconversion can be used to provide a laboratory diagnosis of VZV primary infection .
In order to do this, blood samples must be collected sequentially, with the initial sample needing to be anti-VZV IgG-negative.
the earliest, on the fourth day following the beginning of illnesses, anti-VZV IgM will be detected, typically in conjunction with anti-VZV IgG.
In a country with a universal varicella vaccination program, such as the US, serologic testing for varicella can be more challenging to interpret, due to changes in the course of immunity in vaccinated persons.
In this case.
PCR testing remains the diagnostic test of Therapy for VZV infection General approach In general, children experience a more benign form of varicella compared to adults and adults have a higher incidence of complications.
The majority of varicella infections are self-limiting, treatment is more focused on supportive care and alleviating the discomforts, such as itching which can be very frustrating.
Histamine lotion and a cool bath can be advised in addition to giving nutritious meals to support the speedy recovery.
In contrast, a severe form of varicella may require hospitalization to monitor the potential complication.
Admitted patients should be cared in negative airflow rooms whenever possible.
Airborne and contact precautions should be implemented until all lesions are dry and crusted.
If no negative airflow room is available, patients suffering from varicella should be kept in closed InaJBCS.
Volume 56.
Number 4, 2024 October: 361-376 rooms isolated from others who have no evidence of immunity.
Ideally, only healthcare personnel who have evidence of immunity against varicella can take care of varicella patients.
Antiviral therapy Antiviral clinically severe infections or those at risk of complications due to advanced age .
, immunocompromised conditions, and chronic respiratory or skin diseases.
32 A pathway for determining whether to administer antiviral therapy for primary varicella infection is shown in FIGURE 5.
By administering antiviral therapy.
VZV replication in infected cells can be 53,54 Early treatment, particularly for zoster, may lessen tissue damage and, as a result, the loss of damaged ganglion cells may be slowed down or even be avoided.
For antiviral therapy, the acyclic nucleoside analogs acyclovir, including its prodrug .
, famciclovir .
rodrug of penciclovi.
, and the cyclic nucleoside analog brivudin [(E)-5-.
-bromoviny.
-2A-deoxyuridine.
BVDU], are primarily used.
FIGURE 5.
Therapeutic approach for primary varicella infection.
Annisa L, et al.
Current topics in human varicella.
Antiviral Varicella can be extremely serious and even fatal in specific populations, such as immunocompromised people, expectant mothers, and newborns with no evidence of varicella immunity.
In this case, a post-exposure prophylaxis (PEP) approach is advised to reduce the illness severity and lower the risk of having complications including pneumonitis, rather than to prevent them from contracting the infections.
Previously, a Varicella Zoster Immunoglobulin (VZIG) was recommended routinely to the populations who were concerned about experiencing the severe form of the However, several considerations were put forth afterward, mainly due to the scarcity of VZIG supply, another factor is the evidence of the safety and efficacy of using antivirals for this Currently, the United Kingdom Health Security Agency (UKHSA) recommends antivirals be given as PEP to all at-risk groups with the exception of vulnerable newborns exposed within one week of delivery .
ither in utero or post-deliver.
, while VZIG is given when antivirals are contraindicated only.
The recommended antiviral is acyclovir with a dose of 10 mg/kg body weight .
p to a maximum of 800 m.
four times daily, given from days 7 to 14 after significant exposure to varicella or zoster during the infectious period.
The development of VZV vaccine VZV is the only human herpesvirus for which a licensed live attenuated vaccine has been developed.
This vaccine is based on attenuation of the Oka strain.
56 This vaccine possesses high safety and effectiveness profiles.
significantly reduces the burden of VZVrelated diseases worldwide, although it is far from eradication.
The World Health Organization (WHO) universal vaccination program in countries where varicella become a significant health problem.
After a single dose of varicella protects against all forms of diseases in 76% to 85% of vaccinees and reaches up to 100% after two doses.
It also prevents hospitalization in more than 95% of the vaccines.
57 In the US, with a low vaccination coverage .
urrently 34%), the vaccine annually prevents >120,000 cases of severe cases of HZ.
Among important factors associated with vaccine effectivity is the waning of the immune system with increasing age.
59,60
This phenomenon of immunosenescence reduces the strength and longevity vaccine-induced Overall, 51% of vaccinees Ou60 years of age are protected against HZ.
However, for individuals aged 70 to 79, it drops to 41%, and older vaccinees have even greater declines.
The development of the new vaccine is achieved by designing a subunit vaccine (HZ/s.
composed of the AS01B adjuvant and recombinant VZV gE.
The adjuvant functions to direct the type of immunological response and strengthen it.
The AS01B is made up of liposomes containing the saponin QS21 .
pure extract from the tree Quillaja saponari.
and an agonist of Toll-like receptor 4 (TLR.
, the monophosphoryl lipid A (MPL).
In animal models, the combination of gE and ASO1B stimulates both robust CD4 T cells and antibody Special consideration regarding viral Despite a significant decrease in primary varicella prevalence due to the successful vaccination program, the nature of reactivation in varicella infection is another major concern.
Indeed, some hypotheses are put forth that circulating VZV and periodic InaJBCS.
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Number 4, 2024 October: 361-376 outbreaks of varicella are needed to maintain the community levels of immunity to suppress the incidence of zoster in the adult population who have previously been infected.
57,62
However, this belief is proven to be not Varicella vaccination has been confirmed to induce herd immunity, which protects those who cannot be vaccinated, such as newborns.
63 In addition, zoster incidence also declined significantly among vaccinated children and adolescents, probably as a result of the vaccine strainAos lower reactivation rates compared to the wild-type VZV.
Due to the debilitating impact of zoster, especially on the older age groups, immunization has been strongly advised as a preventive measure.
Previously, a live-attenuated vaccine (ZostavaxA) was approved by the US Food and Drug Administration (US FDA), but later to be discontinued in 2020 due to the high side effects compared to its effectiveness.
Recently, a recombinant subunit vaccine.
ShingrixA, with an overall vaccine efficacy of 97.
2% among participants 50 y.
or older was approved by the US FDA in 2017 and is now recommended by the U.
Centers for Disease Control and Prevention .
he US CDC) as zoster prophylaxis in elderly.
Due to the combination of the benign nature of the primary infection and the successful vaccination, a VZV infection is often overlooked.
One would believe that more investigation into the VZV virus is superfluous given the vaccinesAo Contrarily, there is still much to learn about VZV, a complex and chronic human infection due to its latency.
Surveillance study is needed to fully understand the global health burden associated with varicella, especially in areas where HIV incidence is high.
Reactivation of VZV in the elderly and immunocompromised people following spontaneous infection or immunization is a global concern and results in a debilitating disease that may impair the quality of life.
Since the sequelae are difficult to manage, thus preventing it through vaccination is crucial.
Continued monitoring of the effectiveness and safety of the newly approved zoster subunit vaccine is mandatory, along with better epidemiology surveillance for zoster to assist in informing key health policymakers and later facilitate the implementation of zoster vaccination in a country.
ACKNOWLEDGMENTS
CONCLUSION
Though human VZV infection is often a minor and self-limiting condition, serious consequences can happen.
For this consideration, in 1988.
WHO advised the national varicella vaccine for nations where varicella poses a serious threat to public health.
To date.
VZV is the only human herpesvirus in which an effective vaccine is available.
successful vaccination story of varicella in the US showed the importance of both individual and herd immunity to combat VZV infection.
A long-lasting immunity to either natural or vaccine-derived varicella develops, however, it does not confer protection to the host from virus The authors would like to thank Fatah Manohara for his assistance in preparing the figures.
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