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Arthropod Borne Viruses Arthropods Bilateral symmetry, segmented body, hard exoskeleton, jointed legs, many pairs of legs

Examples y Insects y Arachnids y Crustaceans y Centipedes Prevention & Control of Arbovirus Infection Patient care Disease surveillance & cross-border check Vector control y Search & destroy y Chemical Insecticide, repellent y Biology Fish, bacteria, fungus-like parasite (for Culex mosquitoes) Education Vaccine development Drugs/ other treatment development Detection tool enhancement/ development Further research Quarantine Avoid mosquito bites

Arthropod Borne Viruses (Arboviruses) Family Genus Virus Flaviviridae Flavivirus Dengue, Japanese encephalitis, West Nile, Murray Valley encephalitis Togaviridae Alphavirus Chikungunya, Congo Hemorrhagic Fever Bunyaviridae Nairoviruses Rift Valley fever, Phlebotomus Phleboviruses Arenaviridae Reoviridae Arboviruses Viral encephalitis JE, VEE, WNV, TBE Viral haemorrhagic fever YF, DHF, Crimean-Congo HF Aseptic viral fever DF, CHIK Teratogenic syndrome Main Drain virus, Cache Valley virus Classification of Flavivirus genus

Chikungunya vs Dengue Chikungunya Prolonged joint pain/ arthritis (weeks-months) Haemorrhagic (rare) Thrombocytopenia (rare)

Dengue Myalgia, Arthalgia (bone breaking) Haemorrhagic Thrombocytopenia

Dengue Dengue Flaviviridae family (in Flavivirus genus) Small +ve stranded RNA virus (11kb) Transmitted by female mosquitoes y Aedes aegypti (principal) y Aedes albopictus 4 Serotypes y DEN1 y DEN2 y DEN3 y DEN4 Each serotype provides specific lifetime immunity & short-term cross-immunity 4 Grades of DHF Grade 1 Fever Nonspecific constitutional symptoms +ve tourniquet test (the only hemorrhagic manifestation)

Grade 2 Grade 1 manifestations Spontaneous bleeding

Grade 3 (DSS) Signs of circulatory failure (rapid/ weak pulse, narrow pulse pressure, hypotension, cold/ clammy skin)

Grade 4 (DSS) Profound shock (undetectable pulse & BP)

Tourniquet Test & Petechiae Tourniquet Test


Maintained in zoonotic cycle humans accidental & dead end host Diseases y Non-symptomatic y Undifferentiated fever y Dengue fever y Dengue haemorrhagic fever/ shock syndrome (DSS) In Malaysia, dengue outbreaks occur every 8 years (all 4 serotypes circulate with 1-2 serotypes predominant for several years) Classification of Dengue Course of Dengue Illness

Classification is done after disease has run its course Early febrile illness not easy to predict whether DF or DHF (Close monitoring is important) Clinical Symptoms Dengue Fever Acute fever (3-5d) Incubation 4-7d (range 3-14d) Retro-orbital pain Muscle, bone, joint pain (Myalgia, arthalgia) (bone breaking) Nausea & Vomiting Maculopapular rash Mild hemorrhagic manifestations

Dengue Hemorrhagic Fever Fever Platelet (< 100,000 mm3) Plasma leakage y Hematocrit y Effusion y Hypoproteinaemia Haemorrhagic phenomenon y Skin haemorrhages (petechiae) y Gingival bleeding y Nasal bleeding y Gastro-intestinal bleeding Hepatomegaly Circulatory failure 4 Grades I, II, III, IV

Classification of Dengue Fever & DHF

Risk Factors

Immune Response

Pathogenesis (Antibody Dependent Enhancement) st 1 infection Generate non-neutralizing Abs against other serotypes During 2nd heterotypic infection Abs form complexes with virus (But is not neutralized) Complexes bind to Fc receptor on macrophage/ monocytes Internalisation of DEN Allow greater virus production Infected monocytes release vasoactive mediators Vascular permeability & hemorrhagic manifestations (Characterize DHF, DSS) DHF/ DSS occurs predominantly during secondary infection Immunofluorescent Assay of Dengue Virus

Treatment Vaccine is still under development Supportive treatment only y Monitor o Vital signs (1-2h) o HCT (3-4h) o Urine output y Fluid replacement y Blood transfusion (if necessary)

Diagnosis Clinical laboratory tests y WBC, Platelets, Hematocrit y Albumin y Liver function tests AST, ALT y CXR Dengue specific tests Before Day 5 Antigen detection Nucleic acid detection Viral isolation

After Day 6 Antibody detection (ELISA, HAI, NA) ELISA Results IgM acute infection IgG Previous infection (secondary infection) IgM + IgG secondary infection

Japanese Encephalitis Japanese Encephalitis Family Flaviviridae (genus Flavivirus) (similar to Dengue) Grouped under JE serocomplex group (which includes WNV, St. Louis Encephalitis and others) Vectors Culex spp (Culex tritaeniorhynchus) Effective amplifying hosts y Pigs y Birds Accidental & Dead end host Humans

Chikungunya Chikungunya Togaviridae family, Alphavirus genus Enveloped +ve strand RNA virus (11-12kb) kungunyala bends up Similar vector as Dengue y Aedes ageypti y Aedes albopictus Infection rarely fatal & confers immunity Clinical Presentation Incubation period 3-12d (usually 3-7d) Sudden onset of fever Accompanied by intermittent shaking chills (acute phase 2-3d) Severe arthralgia (many suffer) Migratory polyarthritis (swelling & reddening) y Affects small joints of hands, wrists, ankle, feet y Larger joints, lesser involvement Maculopapular rash (appear 4-8d after infection) Headache Photophobia Anorexia Nausea Conjunctival infection Abdominal pain Recurrent joint pain (older patients)

Clinical Presentation Incubation period 6-16d Infection usually causes subclinical infection Sudden fever, headache, vomiting Resolves in 5-7d if no CNS implication Meningo-encephalitis (1/200 develop) Encephalitic form y Rapid y Headache (2-4d) y Fever, Chills y Anorexia y Nausea/ Vomiting y Dizziness, Drowsiness y Mortality rate Neurologic signs y Dull y Mask-like facial expression y Muscular rigidity y Tremors y Involuntary movements Children y Abdominal pain, Diarrhoea (more prominent) y Convulsions (more common) Poor prognosis y Respiratory dysfunction y Frequent/ prolonged seizures y Prolonged fever y Virus y Levels of IFN in CSF y IgM in serum & CSF Higher risk for fatal infection children, elderly Neuropsychiatric sequelae (45-75% survivors) y Parkinsonism y Seizures y Paralysis y Mental retardation y Psychiatric disorders Diagnosis Viral isolation CSF, serum (less frequent) Viral antigen CSF (in cells) Viral genomic material RT-PCR CSF & serum Antibody detection IgM capture ELISA Treatment/ Prevention No specific therapy Good supportive care Vaccine JE-Vax (from Biken)

CHIKV-associated rheumatism

Polyarthritis Multiple tenosynovitis of wrists & fingers

Hypertrophic tenosynovitis of one ankle

Swelling on right knee

Clinical Presentation Children less severe, less symptoms Infants y Fever y Seizures y Loose stool y Rash y Lethargy y Arthalgia, Arthritis occur (less prominent and at a shorter time) y Bulllous skin lesion (2d after fever) (affect 10-35% body surface) Blister fluid contain virus

Bullous skin lesion

Bullous skin lesion

Diagnosis Similar to DEN (can lead to misdiagnosis) RT-PCR, Antibody detection (IgM/ IgG ELISA), isolation of virus Treatment Self limiting Vaccine (developed, require further testing) Treatment only relieve symptom (joint pain paracetamol, ibuprofen) Movement & mild exercise (improve stiffness & arthalgia) (heavy exercise may exacerbate symptoms)