What Is An Arbovirus?• Arbovirus = arthropod-borne viruses• Arboviruses are maintained in nature through biological transmission between susceptible vertebrate hosts by blood- feeding arthropods• Vertebrate infection occurs when the infected arthropod takes a blood meal
Arboviral Infections.• 100s of Arbovirus,• Around 100 are Human pathogens,• Prevalent in Temperate and Tropical areas.• Most common in tropics,• Out of Many 10 are very important.
Arthropod-borne VirusesArthropod-borneviruses (arbovirus)are viruses that canbe transmitted toman by arthropodvectors. “
The WHO definition is as follows• Viruses maintained in nature principally, or to an important extent, through biological transmission between susceptible vertebrate hosts by haematophagus arthropods or through trans ovarian and possibly venereal transmission in arthropods.”
Arbovirus belong to• Arbovirus belong to three families• 1. Toga viruses e.g. EEE, WEE, and VEE• 2. Bunya viruses e.g. Sandfly Fever, Rift Valley Fever, Crimean-Congo Hemorrhagic Fever• 3. Flavivirus e.g. Yellow Fever, dengue, Japanese Encephalitis
Disease Mechanisms of Toga viruses and Flavivirus Viruses are cytolytic, except for rubella. Viruses establish systemic infection and viremia. Viruses are good inducers of interferon, which can account for the flulike symptoms of infection. Viruses, except rubella and hepatitis C, are arboviruses. Flaviviruses can infect cells of the monocyte-macrophage lineage. Non- neutralizing antibody can enhance flavivirus infection via Fc receptors on the macrophage. Flulike Syndrome Encephalitis Hepatitis Hemorrhage ShockDengue + + + +Yellow fever + + + +St. Louis encephalitis + +West Nile encephalitis + +Venezuelan encephalitis + +Western equine encephalitis + +Eastern equine encephalitis + +Japanese encephalitis + +
Animal ReservoirsIn many cases, the actual reservoir is not known. Thefollowing animals are implicated as reservoirsBirds Japanese encephalitis, St Louisencephalitis, EEE, WEEPigs Japanese encephalitisMonkeys Yellow FeverRodents VEE, Russian Spring-Summerencephalitis
Major Arboviral Diseases1.Yellow fever2.Dengue,3.Japanese B Encephalitis,4.St Louis Encephalitis,5.Russian spring summer encephalitis.6.Eastren Equine Encephalitis,7.West Nile Fever,8.Sand fly Fever
Major Arboviruses That Cause Encephalitis• Flaviviridae – Japanese encephalitis – St. Louis encephalitis – West Nile• Togaviridae – Eastern equine encephalitis – Western equine encephalitis• Bunyaviridae – La Crosse encephalitis
St. Louis Encephalitis• Flavivirus• Most common mosquito- transmitted human pathogen in the US• Leading cause of epidemic flaviviral encephalitis
Eastern Equine Encephalitis• Toga virus• Caused by a virus transmitted to humans and horses by the bite of an infected mosquito.• 200 confirmed cases in the US 1964-present• Average of 4 cases per year• States with largest number of cases – Florida, Georgia, Massachusetts, and New Jersey.• Human cases occur relatively infrequently, largely because the primary transmission cycle takes place in swamp areas where populations tend to be limited.
Western Equine Encephalitis• Toga virus• Mosquito-borne• 639 confirmed cases in the US since 1964• Important cause of encephalitis in horses and humans in North America, mainly in the Western parts of the US and Canada
West Nile virus (WNV)• West Nile virus (WNV) is a mosquito-borne zoonotic arbovirus belonging to the genus Flavivirus in the family Flaviviridae. This flavivirus is found in temperate and tropical regions of the world. It was first identified in the West Nile sub-region in the East African nation of Uganda in 1937.
How the disease manifests• Approximately 80 percent of West Nile virus infections in humans are subclinical, which cause no symptoms. In the cases where symptoms do occur – termed West Nile Fever in cases without neurological disease – the time from infection to the appearance of symptoms (incubation period) is typically between 2–15 days. Symptoms may include fever, headaches, fatigue, muscle pain of aches, malaise, nausea, anorexia vomiting myalgias and rash. Less than 1% of the cases are severe and result in neurological disease when the central nervous system is affected.
La Crosse Encephalitis• Bunya virus• On average 75 cases per year reported to the CDC• Most cases occur in children under 16 years old• Zoonotic pathogen that cycles between the daytime biting tree hole mosquito, and vertebrate amplifier hosts (chipmunk, tree squirrel) in deciduous forest habitats• Most cases occur in the upper Midwestern state, but recently cases have been reported in the Mid- Atlantic region and the Southeast• 1963 – isolated in La Crosse, WI from the brain of a child who died from encephalitis
Togaviridae• The name Togaviridae derived from Toga meaning roman mantle or claok refers to the viral surface
TOGAVIRIDAE Chikungunya virus Infection• 1952 Epidemic in Tanzania.• Manifest as Bend Up with Severe Joint pains.• Spread from wild primates – Mosquito-Man• Appears , reappears,
Indian outbreaks• The virus first appeared in India in 1958 the virus caused large epidemics in Thailand• In 1963 India Chikungunya outbreaks occurred at irregular intervals along the east coast of India and in Maharashtra
Viral Morphology• Spherical 50 - 70 nm• Bears the Nucleocapsid, 42 capsomeres• Positive sense ss stranded RNA
Man to Man infection with Mosquito bites • Chikungunya virus requires an agent for transmission and hence direct human to human transmission is not possible. Usually transmission occurs when a mosquito bites an infected person and then later bites a non infected person.
Flaviviridae Genus – Flavivirus,• Important Diseases, 1. St Louis encephalitis, 2.Ilheus virus 3.West Nile Virus, 4.Murray valley encephalitis, 5.Japanese B encephalitis,
Japanese Encephalitis belongs to Genus Flavivirus• Flaviviridae – Flavivirus• The name is derived from the Latin ‘flavus’ – Flavus means “yellow” • Refers to yellow fever virus• Enveloped• Single stranded RNA virus• Morphology not well defined Center for Food Security and Public Health Iowa State University - 2007
Japanese Encephalitis• First discovered and originally restricted to Japan. Now large scale epidemics occur in China, India and other parts of Asia.• Flavivirus, transmitted by culex mosquitoes.• The virus is maintained in nature in a transmission cycle involving mosquitoes, birds and pigs.• Most human infections are subclinical: the in apparent to clinical cases is 300:1• In clinical cases, a life-threatening encephalitis occurs.• The disease is usually diagnosed by serology. No specific therapy is available.• .
History• 1870s: Japan – “Summer encephalitis” epidemics• 1924: Great epidemic in Japan – 6,125 human cases; 3,797 deaths• 1935: First isolated – From a fatal human encephalitis case• 1938: Isolated from Culex tritaeniorhynchus Center for Food Security and Public Health Iowa State University - 2007
Genus - Flavivirus• Japanese B encephalitis virus is Spherical, 40 – 60 nm in diameter Contain a positive sense Single stranded RNA, 11 kb in size RNA genome is infectious Several viruses in this group are related. Dr.T.V.Rao MD 40
Japanese B virus InfectionInfection is caused by a flavivirus, a single stranded RNA virus. It is transmitted by the bite of the Culex tritaeniorhynchus mosquito. The virus multiplies at the site of the bite and in regional lymph nodes before viraemia develops. Viraemia can lead to inflammatory changes in the heart, lungs, liver, and reticuloendothelial system. Dr.T.V.Rao MD 41
Structure of Virus• The outer envelope is formed by envelope (E) protein and is the protective antigen. It aids in entry of the virus to the inside of the cell. The genome also encodes several non- structural proteins also (NS1,NS2a,NS2b,NS3,N4a,N S4b,NS5). NS1 is produced as secretary form also. NS3 is a putative helicase, and NS5 is the viral polymerase. Dr.T.V.Rao MD 42
A Flavivirus• Japanese encephalitis ( previously known as Japanese B encephalitis is a disease caused by the mosquito-borne Japanese encephalitis virus. The Japanese encephalitis virus is a virus from the family Flaviviridae. Domestic pigs and wild birds are reservoirs of the virus; transmission to humans may occur Dr.T.V.Rao MD 43
INDIAN SCENARIO• Japanese encephalitis ( previously known as Japanese B encephalitis is a disease caused by the mosquito-borne Japanese encephalitis virus. The Japanese encephalitis virus is a virus from the family Flaviviridae. Domestic pigs and wild birds are reservoirs of the virus; transmission to humans may occur D 44
History• 1940-1978 – Disease spread with epidemics in China, Korea, and India• 1983: Immunization in South Korea – Started as early as age 3 – Endemic areas started earlier• 1983-1987: Vaccine available in U.S. on investigational basis Center for Food Security and Public Health Iowa State University - 2007
A leading cause of viral Encephalitis• Japanese encephalitis is the leading cause of viral encephalitis in Asia, with 30,000–50,000 cases reported annually. Case- fatality rates range from 0.3% to 60% and depends on the Dr.T.V.Rao MD 46
Cycle of Infection in Japanese B Viral Infection Dr.T.V.Rao MD 48
Transmission• Vector-borne disease• Enzootic cycle – Mosquitoes: Culex species • Culex tritaeniorhynchus – Reservoir/Amplifying hosts • Pigs, bats • Ardeid (wading) birds • Possibly reptiles and amphibians – Incidental hosts • Horses, humans, others Center for Food Security and Public Health Iowa State University - 2007
A Vector born- Arbovirus Infection• Culex tritaeniorhynchus a rural Mosquito that breeds in rice fields, is the principle vector. In India in 1955 the virus were isolated from Culex vishnui mosquitoes in Vellore region in Tamil Nadu Dr.T.V.Rao MD 50
Japanese Encephalitis (JE)• Most important global cause of arboviral encephalitis with > 50,000 cases and 15,000 deaths reported each year.• Only about 1 in 250 JE infections result in symptomatic illness.• If unrecognized, mortality is up 1 30% with half of• Primarily affects children to survivors sustain age. neurological sequelae. to 15 years of severe• Incubation period is 5 to 14 days.
INCIDENCE• Leading cause of viral encephalitis in Asia with 30-50,000 cases reported annually• Fewer than 1 case/year in U.S. civilians and military personnel travelling to and living in Asia• Rare outbreaks in U.S. territories in Western Pacific Dr.T.V.Rao MD 52
Cycle of Events in Japanese B Encephalitis Dr.T.V.Rao MD 54
Pass through two prominent Hosts• Herons act as reservoir hosts and pigs as amplifier hosts.• Human infection is a tangential ‘dead end’ and infections are spread when the infected mosquitoes reach high density. Dr.T.V.Rao MD 55
Clinical Manifestations• The incubation period is 6 to 16 days.• There is a prodrome of fever, headache, nausea, diarrhoea, vomiting, and myalgia, which may last for several days.• This may be followed by a spectrum of neurological disease ranging from mild confusion, to agitation, to overt coma.• Two thirds of patients have seizures. It is more common in children, while headache and meningism are more common in adults. Dr.T.V.Rao MD 56
Common symptoms of encephalitis Lethargy Sudden fever Headache Change in consciousness Irritability or restlessness Tremors or Vomiting and convulsions diarrhea
Can lead to Neurological damage• Tremor or other involuntary movements are common.• Mutism has been described as a presenting symptom. So has a syndrome of acute flaccid paralysis.• Fever resolves by the second week, and choreoathetosis or extra pyramidal symptoms develop as the other neurological symptoms disappear. Dr.T.V.Rao MD 58
Diagnosis of Japanese B Encephalitis• The isolation of virus from Blood, CSF, or tissues.• Detection of Arbovirus specific RNA in blood,CSF, or Tissue• However very few reference laboratories can perform the isolation in view of the biosafety considerations Dr.T.V.Rao MD 59
Serology by ELISA• IgM capture enzyme-linked immunoassay (ELISA) of serum or CSF is the standard diagnostic test. Sensitivity is nearly 100% when both serum and CSF are tested. False-negatives may result if the samples are tested too early, as in the first week of illness.• New IgM dot enzyme immunoassays for CSF and serum are portable and simple tests that can be used in the field. Compared with ELISA as the gold standard, the sensitivity and specificity are around 98 and 99% respectively. Dr.T.V.Rao MD 60
Arbovirus Specific RNA detection• Viral RNA is extracted from serum or from suspected tissues of the patients or mosquito homogenates.• The product is amplified by RTPCR and the products analyzed by restriction digestion and determined by nucleotide sequence of PCR product.• The identified sequence is compared with nucleotide sequence found in Gene bank or other data bases Dr.T.V.Rao MD 61
Japanese Encephalitis B Vaccine• Japanese Encephalitis B Vaccine has been produced since 1992. The vaccine is effective but not without risks and the substantial risks of the disease and the risks of the vaccine have to be balanced, especially for stays of brief duration. These are discussed more fully in the article on that subject. As with malaria, prophylaxis must be supplemented by techniques to avoid being bitten by mosquitoes. Dr.T.V.Rao MD 62
Preventive measures• Preventive measures include mosquito control and locating piggeries away from human dwellings• A formalin inactivated mouse brain vaccine using the Nakayama strain has been employed in human immunization in Japan – Two doses at two week’s interval followed by a booster 6 – 12 months later constitute a full course.• However the immunity was short lived Dr.T.V.Rao MD 63
Emerging Vaccines for JE virus• Two vaccines are manufactured and distributed exclusively in People’s Republic of China – Inactivated vaccine grown in primary hamster kidney cells – Live attenuated vaccine (SA14-14-2) grown in hamster kidney cells• The third is manufactured in Japan and distributed abroad by arrangement with Sanofi-Pasteur – Licensed as JE-VAXR and is the only FDA approved vaccine for use in the U.S. – Has been in wide use worldwide since the 1960’s – Three subcutaneous injections over a month with a booster at 3 years – 91% efficacy in a large field trial in Thailand
Vaccination• Live attenuated vaccine – Used in equine and swine – Successful for reducing incidence• Inactivated vaccine (JE-VAX) • Used for humans • Japan, Korea, Taiwan, India, Thailand • Used for endemic or epidemic areas – Recommended for travelers • Visiting endemic areas for > 30 days Center for Food Security and Public Health Iowa State University - 2007
Later vaccines• A live attenuated vaccine has been developed in China from JE strain SA 14-14-2, passed through weanling mice• The vaccine is produced in primary bay hamster kidney cells.• Administered in two doses, one year apart, the vaccine has been reportedly effective in preventing clinical disease Dr.T.V.Rao MD 66
Prevention• Vector control – Eliminate mosquito breeding areas – Adult and larvae control• Vaccination – Equine and swine – Humans• Personal protective measures – Avoid prime mosquito hours – Use of repellants containing DEET Center for Food Security and Public Health Iowa State University - 2007
Yellow Fever, Flaviviridae - Family• Mosquito Borne disease• Present in Africa, Central and South America.• Absent in India.
Flavivirus• Spherical 40-60 nm in diameter glycosylated. Diameter,• Ss-RNA positive sense• Three or Four structural polypeptides, Two are glycosylated.• Replicates in Cytoplasm.• Produces Councilman bodies
Pathogenesis and Pathology• Mosquito ( Ades aegypti )Through skin- Lymphatics, Lymph nodes, circulation liver, Spleen, Kidney, Bone marrow, Lymph glands. Necrotic lesions in liver , kidney,Mid zone – liverFatty degeneration – kidney,Hemorrhages/Circulatory collapse.Injury to Myocardium
Clinical Features• Incubation period 3-6 days,• Fever, chills,• Intoxication, Fever, Jaundice• Clotting disorders,• Mortality > 20%• May recover totally
Laboratory Diagnosis• Intracerebral inoculation,• Mosquito cell lines,•PCR• Serology – ELISA Ig M Raise of titers,
Immunity and Epidemiology• Nt Antibodies protects,• Epidemiology Urban yellow fever, Jungle yellow fever. Monkey, Not Invaded Asia Not present in India.
Immunity and Epidemiology• Nt Antibodies protects,• Epidemiology Urban yellow fever, Jungle yellow fever. Monkey, Not Invaded Asia Not present in India.
Treatment and Prevention.• No Antiviral drugs,• Mosquito control• Vaccine 17 D strain of yellow fever vaccine.• A single dose protect 95% of vaccinated.• Not to be given in infants < 9 months age.
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