Chickenpox: Pathophysiology

Varicella-zoster virus is responsible for causing a primary varicella infection (chickenpox) and a secondary herpes zoster infection (shingles). Although varicella typically manifests as a mild disease in otherwise healthy children, it can also manifest as a moderate-to-severe disease, most notably in immunocompromised and adult hosts. Acyclovir is the antiviral agent of choice for the management of varicella infections. Routine vaccination with Varivax has been very effective in reducing chickenpox incidence

1. Medical Microbiology & Infectious Disease Assignment TOPIC- CHICKENPOX Submitted by NIMRA NEYAZ B.Sc (H)Medical Biotechnology BSM/14/116 VIIth Semester Amity Institute of Biotechnology

2. CHICKENPOX ETIOLOGY Causative Organism- Varicella Zoster Virus , which belongs to Alpha sub-family of Herpes virus family. VZV is also known as Human Herpes 3 virus Host- man; Reservoir- infected individuals VZV is an enveloped, double-stranded DNA virus. Chickenpox is the manifestation of primary infection Shingles(zoster) is the manifestation of the reactivated latent infection of endogenous VZV.

3. Structure of VZV Lipid envelope studded with spiky glycoproteins which help in attachment with host cell receptors . Tegument made of viral proteins, containing DNA polymerases . Icosahedral nucleocapsid Core contains linear double stranded DNA

4. Mode Of Transmission Direct contact with the lesions. Droplet infection Air-borne Brief Epidemiology Occurs as both Epidemic and Endemic forms in India. In temperate climates, it exhibits an annual epidemic trend, peaking in late winter to spring Historically, children between the ages of 1 and 4 years accounted for 39% of cases, while children aged 5 to 9 years and adults ≥20 years accounted for 38% and 7%, respectively (National Health Interview Survey data, 1990-1994). Newborns, pregnant women more susceptible, immune-compromised patients are also at greater risk. The virus can cross placental barrier leading to Congenital Varicella Syndrome

5. SYMPTOMS & CLINICAL FEATURES Incubation period= 10-21 days Takes usually 1-3 weeks for symptoms to appear Mild fever Rashes on trunk, face, arms and legs

6. Chickenpox rash develops in 3 stages

7. Life Cycle of Varicella zoster virus Enveloped VZV particles attach to cell membranes with Mannose-6-phosphate receptor fuse and release of tegument proteins.(Receptor-Mediated Endocytosis) genomic DNA is injected into the nucleus and circularizes. immediate-early genes expressed, followed by early and late genes. Nucleocapsids are assembled and package newly synthesized genomic DNA, move to the inner nuclear membrane and budding across nuclear membrane. Capsids enter the cytoplasm, and virion glycoproteins mature in the  trans -Golgi region and tegument proteins assemble in vesicles; capsids undergo secondary envelopment and are transported to cell surfaces newly assembled virus particles released .

8. PATHOPHYSIOLOGY Route of infection-Mucosa of upper respiratory tract or conjunctiva Local replication followed by spread to tonsils and other regional lymphoid tissues, where VZV gains access to T cells(CD4+ & CD8+) Infected T cells then deliver the virus to cutaneous sites of replication. Vesicular rashes develop by the end of 10 th day. VZV establishes latency in sensory ganglia after transport to neuronal nuclei along neuronal axons or by viraemia . Reactivation from latency enables a second phase of replication to occur in skin, which typically causes lesions in the dermatome that is innervated by the affected sensory ganglion.

9. Recent study

10. DIAGNOSIS Enzyme immunoassay-detects rise in Varicella Immunoglobin G Fluorescent Antibody testing ELISA Tzanck smear Detection of viral DNA by PCR Culture of lesion samples

11. COMPLICATIONS Pneumonia Encephalitis Reye Syndrome (acute encephalopathy along with fatty degeneration of liver) Hemorrhage Septicemia

12. PROPHYLAXIS Two doses of live-attenuated vaccines(VARIVAX)-1 st dose at 12-15 months of age & 2 nd dose around 4-6 years of age. It is a single-agent vaccine containing a live, attenuated (Oka strain) virus Varicella Zoster Immunoglobin( VariZIG ) is effective in preventing the disease if given within 96 hours of exposure . provides passive immunity to persons at high risk of severe chickenpox

13. TREATMENT Some Symptomatic measures include: Good hygiene (e.g., daily baths, preferably with antibacterial soap) and thorough skin care are important for the prevention of secondary bacterial infections Further measures of supportive therapy include OTC medications such as acetaminophen for fever, topical agents that include calamine, daily lukewarm soaks with colloidal oatmeal, and oral or topical antihistamines; the latter three will provide management and a soothing relief of the pruritus The child’s fingernails should also be cut short in an effort to prevent secondary bacterial skin infections Antiviral medication only when the case is severe(It is advisable to let the disease complete its course) Acyclovir is given which is a viral DNA polymerase inhibitor. Immunoglobin intravenous( Privigen ) can also be given to lessen the severity of the disease. .

14. Antiviral therapy Fig: Mechanism of action of Acyclovir in cells infected with Varicella Zoster Virus

15. Acyclovir, an antiviral agent used in the management of varicella, is available in both oral and IV formulations. It is an acyclic analogue of guanosine that must be phosphorylated by viral thymidine kinase and subsequently by host cell enzymes into its active triphosphate form for its antiviral activity through inhibition of viral DNA polymerase ( Acyclovir is the antiviral agent of choice in the treatment of varicella and should be initiated within 24 hours of the onset of rash. It has been proven to shorten both the duration and severity of chickenpox by decreasing viral shedding and the formation of new lesions, as well as by accelerating lesion healing in both healthy and immunologically compromised children

16. References World Health Organization – position paper, Chickenpox vaccine; Weekly epidemiological record. 1998, 73 :241-248. Heymann L D 2004, Chickenpox control of communicable diseases manual, 18th edition Freer G, Pistello M. Varicella-zoster virus infection: natural history, clinical manifestations, immunity and current and future vaccination strategies. New Microbiol. 2018 Apr;41(2):95-105. Dayan RR, Peleg R. Herpes zoster - typical and atypical presentations. Postgrad Med. 2017 Aug;129(6):567-571. Heininger U., Seward J.F. Varicella. Lancet. 2006;368:1365–1376. Cohen JI, Brunell PA, Straus SE, Krause PR. Recent advances in varicella-zoster virus infection. Ann Intern Med. 1999;130:922-932. American Academy of Pediatrics. Committee on Infectious Diseases. Varicella vaccine update. Pediatrics. 2000;105:136-141.

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