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chikungunya disease and it's pathophysiology
1. GURU GHASIDAS VISHWAVIDYALAYA
KONI, BIL ASPUR (C.G.)
By Parth Sharma
M.Sc. iii semester
Department of Biotechnology
TOPIC OF PRESENTATION
CHIKUNGUNYA DISEASE
2.
3. 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
4. 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.
5. FIGURE: SPREAD OF CHIKV LINEAGES
La reunion
France
Italy
Caribbean
Latin America Tanzania
6. VECTOR
6
Vector of CHKIV is Aedes mosquitoes. Different species of aedes that cause
chikungunya disease are:
1. A furcifer-taylori
2. A africanus
3. A luteocephalus act as vector to infect nonhuman primates
4. A neoafricanus
5. A aegypti
6. 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
8. 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.
10. 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.
13. 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.
15. 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
16. VACCINES
20XX PRESENT A TI O N 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
17. TREATMENT
NSAIDS
naproxen,
ibuprofen,
diclofenac or
aceclofenac
HYDROXYCHL
OROQUINE
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
18. 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
Editor's Notes
Symmetric pain
Heparan sulfate proteoglycans (HSPGs): These are molecules that are present on the surface of many cell types and have a role in cell adhesion and signaling. They have been shown to facilitate the attachment of CHIKV to various cell lines and primary cells, such as fibroblasts, endothelial cells, and monocytes.
Ribavirin is an antiviral medication that is used to treat some viral infections, such as hepatitis C, respiratory syncytial virus, and some viral hemorrhagic fevers. ¹ It works by interfering with the synthesis of viral RNA and mRNA, which are essential for the replication and expression of the virus. ² Ribavirin is always used in combination with other drugs, such as interferon-alpha or direct-acting antivirals, to increase the effectiveness and reduce the resistance of the treatment. ¹ Ribavirin can cause serious side effects, such as anemia, liver problems, and birth defects. Therefore, it should be used with caution and under medical supervision. ¹³
Flavipiravir is a misspelling of favipiravir, which is an antiviral medication used to treat influenza in Japan and some other viral infections, such as COVID-191 Favipiravir works by inhibiting the viral RNA-dependent RNA polymerase, which is essential for the replication and expression of the virus2 Favipiravir is a prodrug that is metabolized to its active form, favipiravir-RTP, in the body3 Favipiravir has some side effects, such as increased uric acid level, diarrhea, decreased white blood cell count, and increased liver enzymes. Favipiravir should not be used during pregnancy, as it can cause harm to the baby. Favipiravir is sold under various brand names, such as Avigan, Avifavir, Areplivir, and others1