chikungunya disease and it's pathophysiology

this ppt deals with the overall information about the chikungunya disease.

1. Guru ghasidas Vishwavidyalaya Koni, bilaspur ( c.g. ) By Parth Sharma M.Sc. iii semester Department of Biotechnology Topic of presentation Chikungunya disease

2. Introduction Chikungunya is an arboviral infection that is characterized by severe polyarthralgia and myalgia. It is caused by Chikungunya virus (CHIKV) which is an Aedes mosquito-borne Alphavirus belongs to family Togaviridae . CHIKV was first discovered in 1952 on the Makonde Plateau in East Africa (present day Tanzania). The word chikungunya is derived from the Kimakonde root verb kungunyala meaning “that which bends up”, “to become contorted” or “to walk bent over”. . 20XX 3

3. Epidemiology Phylogenetic analysis identified three distinct lineages corresponding to their respective geographical origin: West African, East Central South African (ECSA) and Asian lineage . Since its discovery in 1952, CHIKV has been reported to be circulating and causing sporadic outbreaks in sub-Saharan Africa. In 2004, a large-scale CHIKV epidemic erupted, in Kenya and subsequently spread to the Indian Ocean Islands, particularly in La Réunion ( Indian Ocean lineage ). 266,000 cases on an island with a population of approximately 770,000. In 2006, India reported 1.25 million suspected cases. Autochthonous transmission of CHIKV was observed for the first time in Italy in 2007, and in France in 2009. In December 2013, the first cases of locally transmitted CHIKV in the Americas were confirmed in St. Martin, followed by throughout the Caribbean and Latin America. In 2014, the ECSA lineage was reported in North-east Brazil, where it continues to circulate as the most prevalent strain. By January 2015, CHIKV infection had been identified in 42 countries or territories in the Caribbean, Central America, South America, and North America (local transmission in Florida) with more than a million suspected cases reported, and more than 25,000 laboratory-confirmed.

4. Figure: spread of CHIKV lineages La reunion France Italy Caribbean Latin America Tanzania

5. vector 6 Vector of CHKIV is Aedes mosquitoes. Different species of aedes that cause chikungunya disease are: A furcifer-taylori A africanus A luteocephalus act as vector to infect nonhuman primates A neoafricanus A aegypti A albopictus An important factor that facilitated the rapid expansion of CHIKV infection was a novel single amino acid substitution of alanine for valine at position 226 (A226V) in the E1 envelope protein that enhanced the ability of the Aedes albopictus mosquito to transmit CHIKV to humans. act as vectors to infect humans

6. Life cycle of CHIKV

7. symptoms A sudden onset of high fever above 39 °C (102 °F). The fever is soon followed by severe muscle and joint pain. Pain usually affects multiple joints in the arms and legs People with Chikungunya also frequently experience headache, back pain, nausea, and fatigue. Rash, with reddening and sometimes small bumps on the palms, foot soles, torso, and face also developed in affected person. These are the first set of symptoms – called the "acute phase" of Chikungunya – lasts around a week, after which most symptoms resolve on their own. Many people continue to have symptoms after the "acute phase" resolves, termed the "post-acute phase" for symptoms lasting three weeks to three months, and the "chronic stage" for symptoms lasting longer than three months.

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9. Virus structure 10 CHIKV virus contain a single 11.8-kbp strand of positive sense RNA , which encodes The polyproteins give rise to the four nonstructural proteins (nsP1-4) that make up the viral replication machine, and five structural proteins . CHKIV is spherical viral particle the diameter is approximately 70 nm and the genomic RNA, encapsulated by capsid (C) proteins. Capsid protein is surrounded by a host cell–derived lipid bilayer spiked with heterodimers of envelope proteins E1 and E2. The envelope proteins, E2 and E1, play important roles in the binding of the virus to the host cell membrane and its subsequent cellular invasion, respectively. The other two structural proteins, 6K and E3, are leader peptides for E1 and E2, respectively. a 2472 amino acid nonstructural protein a 1244 amino acid structural polyprotein .

10. 11 70 nm

11. Pathogenesis 12

12. CHKIV infection & replication 13 Infection starts with cellular entry after receptor binding and clathrin -mediated endocytosis Viral genomic RNA (gRNA) is released into the cytoplasm following E1-mediated fusion of virion and endosomal membrane, and is translated to produce the non-structural proteins ( nsPs ) that form the replicase complex. The replicase complex is then translocated to the plasma membrane to form replication spherules, the neck of which is formed by a 12-mer nsP1 ring and in which nsP4 RNA-dependent, RNA polymerase activity-mediated, negative-strand and new positive-strand viral gRNA and sub-genomic RNA (sgRNA) production takes place. sgRNA is translated to produce the structural polyprotein C–E3–E2–6K/TF–E1 Capsid is autoproteolytically cleaved through its own protease activity to remain cytoplasmic. The envelope proteins are produced at the endoplasmic reticulum membrane and mature after cleavage by trans-Golgi network-localized Furin proteases and glycosylation Packaging of viral gRNA into virions is induced by capsid binding to gRNA-specific sequences, avoiding packaging of sgRNA. E2 and E1 are type I transmembrane proteins and form heterodimers, three of which form a trimeric spike; 80 of these trimeric spikes are presented on the viral particle.

13. 20XX PRESENTATION TITLE 14

14. Diagnosis 15 Test Detection target Interpretation Advantages Limitations Culture test Viable virus Acute infection Highly specific; can be quantitative; isolate can be further characterized Requires specialized containment facility; can take days for a result reverse transcription–PCR Viral RNA Acute infection Highly sensitive and specific; multiplex, point-of-care testing available; time to result: 1–3 h Expensive; requires equipment Serological methods or immunoassay IgM antibodies High level of IgM antibodies is suggestive of recent infection (~2 months) lateral flow rapid tests that can be used outside of laboratory settings IgM antibodies tend to persist for months; antibodies may be cross-reactive with those of other alphaviruses, giving a false positive result A fourfold rise in IgG antibody titer; IgM/IgG seroconversion Definitive evidence of infection Retrospective diagnosis of chikungunya virus infection Requires collection of a second blood sample 7–14 days after the first sample

15. Vaccines 20XX PRESENTATION TITLE 16 Vaccine Type Virus strain Advantages Limitations Status VLA1553 (Valneva) Live attenuated virus La Réunion Island, 2006 Rapid immune response (<14 days); single dose Transient arthralgia and fever; cannot use in pregnancy or immunocompromised; durability >1 year unknown Approved by FDA in 2023 (first vaccine) PXVX0317 (Bavarian Nordic) Virus-like particle plus adjuvant Senegal, 1983 Rapid immune response (<14 days); durable immune response (2 years); thermostable; single dose; platform safe in pregnancy and immunocompromised Requires an adjuvant Phase III trail compilated V184 (Themis Bioscience) Recombinant vector vaccine (Measles vector) La Réunion Island, 2006 Platform based on the highly safe, effective and durable measles vaccine; also boosts measles immunity May require 2 doses; durability >224 days unknown; cannot use in pregnancy or immunocompromised Phase III trial not started BBV87 (Bharat Biotech International Ltd’s ) Inactivated virus plus adjuvant India, 2006 Thermostable; platform safe in pregnancy and immunocompromised Phase I data not published yet; requires 2 doses; requires an adjuvant Phase III trails are ongoning

16. Treatment NSAIDs naproxen, ibuprofen, diclofenac or aceclofenac hydroxychloroquine In the event of musculoskeletal symptoms Ribavirin Inhibits viral genome replication by depleting guanosine triphosphate Favipiravir Inhibits viral genome replication DMARDs Used in the treatment of chronic chikungunya fever with beneficial effects in the control of joint symptoms related to the chronic pro-inflammatory process ex. Methotrexate

17. Conclusion Considerable progress has been made to identify key host molecules involved in CHIKV infection but further studies are still required to validate these findings in relevant cellular systems, animal models and patients. Interdisciplinary research basic biomedical research of the interactions between the virus, mosquito vector and human host is required for a better understanding of transmission dynamics, to develop better diagnostic tools and to disentangle chronic pathogenesis, including chronic forms. 18