Arbovirus Part II

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Arbovirus Part II


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Arthropod-borne Viruses Part II Dr.T.V.Rao MD Dr.T.V.Rao MD 1

Arthropod-borne Viruses:

Arthropod-borne Viruses Arboviruses belong to three families 1. Togaviruses e.g. EEE, WEE, and VEE 2. Bunyaviruses e.g. Sandfly Fever, Rift Valley Fever, Crimean-Congo Haemorrhagic Fever 3. Flavivirus e.g. Yellow Fever, Dengue, Japanese Encephalitis Dr.T.V.Rao MD 2




Arboviruses The Arbovirus are also called as Arthropod borne viruses, represent an ecological grounding of viruses with complex transmission cycles involving Arthropods These viruses have diverse physical and chemical properties and are classified in several virus families. Dengue infection is caused by Arbovirus Dr.T.V.Rao MD 4

Man-Arthropod-Man Cycle :

Man-Arthropod-Man Cycle Dr.T.V.Rao MD 5

History - Dengue :

History - Dengue This disease was first described 1780, and the virus was isolated by Sabin 1944. Dengue virus infection is the most common arthropod-borne disease worldwide with an increasing incidence in the tropical regions of Asia, Africa, and Central and South America. Dr.T.V.Rao MD 6

Over view of Dengue:

Over view of Dengue With more than one-third of the world’s population living in areas at risk for transmission, dengue infection is a leading cause of illness and death in the tropics and subtropics. As many as 100 million people are infected yearly. Dengue is caused by any one of four related viruses transmitted by mosquitoes Dr.T.V.Rao MD 7

Dengue :

Dengue Dengue  is the biggest Arbovirus problem in the world today  with over 2 million cases per year. Dengue is found in SE Asia, Africa and the Caribbean and S America. Flavivirus, 4 serotypes, transmitted by Aedes mosquitoes which reside in water-filled containers. Human infections arise from a human-mosquitoe-human cycle . Dr.T.V.Rao MD 8

Current Trends:

Current Trends In the 1980s, DHF began a second expansion into Asia when Sri Lanka, India, and the Maldives Islands had their first major DHF epidemics; Pakistan first reported an epidemic of dengue fever in 1994.. Dr.T.V.Rao MD 9

Distribution of Dengue:

Distribution of Dengue Dr.T.V.Rao MD 10

Dengue Infection and Implications:

Dengue Infection and Implications Dengue virus (DENV) infects 50 million (WHO) to 100 million (NIH) people annually. Forty per cent of the world’s population, predominately in the tropics and sub-tropics, is at risk for contracting  dengue virus. DENV infection can cause dengue fever, dengue haemorrhagic fever, dengue shock syndrome, and death. Dr.T.V.Rao MD 11

Dengue Mosquito transmitted Viral Infection:

Dengue Mosquito transmitted Viral Infection Dr.T.V.Rao MD 12

What causes Dengue:

What causes Dengue Dengue (DF) and dengue haemorrhagic fever (DHF) are caused by one of four closely related, but antigenic ally distinct, virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4), of the genus Flavivirus . Infection with one of these serotypes provides immunity to only that serotype for life, Dr.T.V.Rao MD 13

Aedes aegypti – Vector :

Aedes aegypti – Vector Aedes aegypti , a domestic, day-biting mosquito that prefers to feed on humans, is the most common Aedes species. Infections produce a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal haemorrhagic disease. Other species of Aedes can also transmit. Dr.T.V.Rao MD 14

Dengue Virus – A Flavivirus:

Dengue Virus – A Flavivirus Flavivirus are spherical and 40- 60 mm in diameter. Genome – Positive sense, single sense RNA,11kb in size Genome – RNA infectious Enveloped virus Three structural polypeptides two are glycosylated Replication in cytoplasm Dr.T.V.Rao MD 15

How Mosquitos spread the infection:

How Mosquitos spread the infection The disease starts during the rainy season, when vector Mosquito Aedes aegypti is abundant The Aedes breeds in the tropical or semitropical climates in water holding receptacles or in plants close to human dwellings A female Aedes acquires the infection feeding upon a viremic human. After a period of 8 – 14 days mosquitoes are infective and remain infective for life. ( 1- 3 ) months. Dr.T.V.Rao MD 16


Pathogenesis Presence of existing Dengue antibody, associated with fresh viral infection with new serotype complexes and forms within few days of the second dengue infection. Non neutralizing enhancing antibodies promote infection of higher number of Mononuclear cells. Dr.T.V.Rao MD 17

Immunology Dengue:

Immunology Dengue Four serotypes exist distinguished by Molecular basis and Nt tests Infection confers life long immunity But cross protection between serotypes is of short duration. Reinfection with different serotype after primary attack is more dangerous causes Dengue hemorrhagic fever . Dr.T.V.Rao MD 18

Clinical Manifestations:

Clinical Manifestations Any or few of the following events can occur. Fever, Severe head ache Muscle and joint pains Nausea, vomiting, Eye pain Dr.T.V.Rao MD 19

How Dengue Infection starts and manifests:

How Dengue Infection starts and manifests Incubation period 4 – 7 days ( 3 – 14 days) Fever may start with, Malise,chills,head ache Soon leads to severe back ache, joint pains, muscular pain, pain in the eye ball. Temperature may persist for 3 -5 days. On some occasions once again raises in about 5 – 8 days ( Saddle back fever ) Myalgia may be severe with deep bone pain ( Break bone fever ) characteristic of the Disease On majority of the occasions a self limited condition, Subside on its own Death is a rare event. Dr.T.V.Rao MD 20

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Dr.T.V.Rao MD 21

Dengue with Rashes:

Dengue with Rashes Dr.T.V.Rao MD 22

Dengue Hemorrhagic Fever:

Dengue Hemorrhagic Fever DHF was first recognized in the 1950s during the dengue epidemics in the Philippines and Thailand . Today emerging DHF cases are causing increased dengue epidemics in the Americas, and in Asia, where all four dengue viruses are endemic, DHF has become a leading cause of hospitalization and death among children in several countries . ( WHO ) Dr.T.V.Rao MD 23

Dengue Hemorrhagic Fever:

Dengue Hemorrhagic Fever Common in children. In children passively acquired contributed by the maternal antibodies transferred to the fetus. In other ( Adults ) the presence of antibodies due to previous infection with different serotype Initially presents like classical Dengue infection But patients condition abruptly worsens, an important cause of morbidity and mortality in Dengue Dr.T.V.Rao MD 24

Basic Understanding of Dengue Hemorrhagic Fever:

Basic Understanding of Dengue Hemorrhagic Fever Dengue Hemorrhagic Fever is a probable case of dengue and hemorrhagic tendency evidenced by one or more of the following: Ø Positive tourniquet test Ø Petechial, ecchymosis or purpura Ø Bleeding from mucosa (mostly epistaxis or bleeding from gums), injection sites or other sites Ø Haematemesis or melena Dr.T.V.Rao MD 25

How to do a Tourniquet test:

How to do a Tourniquet test The tourniquet test is performed by inflating a blood pressure cuff to a point mid-way between the systolic and diastolic pressures for five minutes. A test is considered positive when 10 or more petechiae per 2.5 cm2 (1 inch) are observed. In DHF, the test usually gives a definite positive result (i.e. >20 petechiae). The test may be negative or mildly positive during the phase of profound shock. Dr.T.V.Rao MD 26

What Happens in Dengue Hemorrhagic Fever:

What Happens in Dengue Hemorrhagic Fever Thrombocytopenia (platelets 100,000/ or less) and Ø Evidence of plasma leakage due to increased capillary permeability manifested by one or more of the following: – A >20% rise in hematocrit for age and sex – A >20% drop in hematocrit following treatment with fluids as compared to baseline – Signs of plasma leakage (pleural effusion, ascites or hypoproteinaemia). Dr.T.V.Rao MD 27

Risk factor for DHF:

Risk factor for DHF Important risk factors for DHF include the strain of the infecting virus, as well as the age, and especially the prior dengue infection history of the patien t Dr.T.V.Rao MD 28

Dengue Hemorrhagic Syndrome:

Dengue Hemorrhagic Syndrome Chateresied by shock and hemoconcentration Contributed by circumstantial evidence suggests secondary infection with Dengue type 2 following type 1 infection in the past. Dr.T.V.Rao MD 29

Dengue hemorraghigic Syndrome:

Dengue hemorraghigic Syndrome DHS is caused due to release of, 1 Release of cytokines 2 Vasoactive mediators. 3 Procoagulants Manifest with disseminated intravascular coagulation Dr.T.V.Rao MD 30


Diagnosis In resource rich establishments 1 Reverse transcriptase polymerase chain reaction methods help rapid identification 2 Isolation of virus is difficult 3 The current favored approach is inoculation of mosquito cell line with patient serum coupled with nucleic acid assay to identify a recovered virus. Dr.T.V.Rao MD 31

Dengue Serology:

Dengue Serology The serology is limited with cross reactivity of IgG antibodies to heterologous Flavivirus antigens Most commonly used methods are Viral protein specific capture IgM or IgG by ELISA IgM antibodies develop within few days of illness Neutralizing anti Haemagglutination inhibiting antibodies appear within a week after onset of Dengue fever Dr.T.V.Rao MD 32

Importance of paired sample testing in Serology:

Importance of paired sample testing in Serology Testing one sample for serum and reporting a negative test is fallacious Analysis of paired acute and convalescent sera to show significant rise in antibody titer is the most reliable evidence of an active dengue infection . Dr.T.V.Rao MD 33

Newer Diagnostic Methods RT - PCR:

Newer Diagnostic Methods RT - PCR RT PCR is a highly sensitive tool in Diagnosis, with established high sensitivity in Diagnosis in Puzzles Developing world lacks resources to implement and utilize the Scientific advances Dr.T.V.Rao MD 34

Treatment :

Treatment No Anti viral therapy available Symptomatic management in Majority of cases Dengue Hemorrhagic fever to be treated with suitable fluid replacement No Vaccine available, difficult in view of four serotypes. Dr.T.V.Rao MD 35

Control of Dengue:

Control of Dengue Control of Mosquito breeding places. Anti mosquito measures Use of Insecticides. Screened windows and doors can reduce exposure to vectors. Dr.T.V.Rao MD 36

Epidemiology - Dengue:

Epidemiology - Dengue Dengue virus are distributed world wide in tropical regions. Where the Aedes vectors exist, are endemic areas Changing and increasing incidences are associated with rapid urban population growth, over crowding and lax mosquito control measures Dr.T.V.Rao MD 37

Viral Hemorrhagic Fevers :

Viral Hemorrhagic Fevers Dr.T.V.Rao MD 38

Viral Haemorrhagic Fevers :

Viral Haemorrhagic Fevers Acute infection: fever, myalgia, malaise; progression to prostration Small vessel involvement: increased permeability, cellular damage Multisystem compromise (varies with pathogen) Hemorrhage may be small in volume (indicates small vessel involvement, thrombocytopenia) Poor prognosis associated with: shock, encephalopathy, extensive hemorrhage Dr.T.V.Rao MD 39

Viral Hemorrhagic Fevers:

Viral Hemorrhagic Fevers Diverse group of illnesses caused by RNA viruses from 4 families: Arenaviridae, Bunyaviridae, Filoviridae, Flaviridae Differ by geographic occurrence and vector/reservoir Share certain clinical and pathogenic features Potential for aerosol dissemination, with human infection via respiratory route (except dengue) Target organ: vascular bed Mortality 0.5 - 90%, depending on agent Dr.T.V.Rao MD 40

Viral Hemorrhagic Fever viruses:

Viral Hemorrhagic Fever viruses Filoviruses Ebola Hemorrhagic fever (EHF) Marburg virus Arenaviruses Lassa fever “New World Arenaviruses” Bunyaviruses Rift Valley fever (RVF) Crimean Congo Hemorrhagic fever (CCHF) Dr.T.V.Rao MD 41

Viral Hemorrhagic Fevers:

Viral Hemorrhagic Fevers Category A agents Filoviruses Arenaviruses Category C agents Hantaviruses Tick-borne hemorrhagic fever viruses Yellow fever Dr.T.V.Rao MD 42

Viral Hemorrhagic Fevers Transmission:

Viral Hemorrhagic Fevers Transmission Zoonotic diseases Rodents and arthropods main reservoir Humans infected via bite of infected arthropod, inhalation of rodent excreta, or contact with infected animal carcasses Person-to-person transmission possible with several agents Primarily via blood or bodily fluid exposure Rare instances of airborne transmission with arenaviruses and filoviruses Rift Valley fever has potential to infect domestic animals following a biological attack Dr.T.V.Rao MD 43

Viral Hemorrhagic Fevers Clinical Presentation:

Viral Hemorrhagic Fevers Clinical Presentation Clinical manifestations nonspecific, vary by agent Incubation period 2-21 days, depending on agent Onset typically abrupt with filoviruses, flaviviruses, and Rift Valley fever Onset more insidious with arenaviruses Dr.T.V.Rao MD 44

Viral Hemorrhagic Fevers Initial Symptoms:

Viral Hemorrhagic Fevers Initial Symptoms High fever Headache Malaise Weakness Exhaustion Dizziness Muscle aches Joint pain Nausea Non-bloody diarrhea Prodromal illness lasting < 1 week may include: Dr.T.V.Rao MD 45

VHF Surveillance: Clinical Identification of Suspected Cases :

VHF Surveillance: Clinical Identification of Suspected Cases Clinical criteria: Temperature 101  F(38.3 C) for <3 weeks Severe illness and no predisposing factors for hemorrhagic manifestations 2 or more of the following: Hemorrhagic or purple rash Epistaxis Hematemesis Hemoptysis Blood in stools Other hemorrhagic symptoms No established alternative diagnosis JAMA 2002;287 Adapted from WHO Dr.T.V.Rao MD 46

Viral Hemorrhagic Fevers Treatment:

Viral Hemorrhagic Fevers Treatment Supportive care Correct coagulopathies as needed No antiplatelet drugs or IM injections Investigational treatments, available under protocol: Ribavirin x 10 days for arenaviridae and bunyaviridae Convalescent plasma w/in 8d of onset for AHF Dr.T.V.Rao MD 47

Viral Hemorrhagic Fevers Management of Exposed Persons:

Viral Hemorrhagic Fevers Management of Exposed Persons Medical surveillance for all potentially exposed persons, close contacts, and high-risk contacts (i.e., mucous membrane or percutaneous exposure) x 21 days Report hemorrhagic symptoms (slide 47) Record fever 2x/day Report temperatures  101 F(38.3C) Initiate presumptive ribavirin therapy Percutaneous/mucocutaneous exposure to blood or body fluids of infected: Wash thoroughly with soap and water, irrigate mucous membranes with water or saline Dr.T.V.Rao MD 48

Viral Hemorrhagic Fevers Infection Control :

Viral Hemorrhagic Fevers Infection Control Airborne & contact precautions for health care, environmental, and laboratory workers Negative pressure room, if available 6-12 air changes/hour Exhausted outdoors or through HEPA filter Personal protective equipment Double gloves Impermeable gowns, leg and shoe coverings Face shields and eye protection N-95 mask or PAPR Dr.T.V.Rao MD 49

Tick Borne Hemorrhagic Fevers:

Tick Borne Hemorrhagic Fevers Kyasanur Forest Disease, ( Karnataka India ) Like Russian Spring Summer Encephalitis, Present with Fever, Headache, Conjunctivitis, Myalgia, Severe prostration, Dr.T.V.Rao MD 50

Viral Hemorrhagic Fevers Infection Control :

Viral Hemorrhagic Fevers Infection Control Dedicated medical equipment for patients If available, point-of-care analyzers for routine laboratory analyses If unavailable, pretreat serum w/Triton X-100 Lab samples double-bagged & hand-carried to lab Prompt burial or cremation of deceased with minimal handling Autopsies performed only by trained personnel with PPE Dr.T.V.Rao MD 51

Viral Hemorrhagic Fevers Summary of Key Points :

Viral Hemorrhagic Fevers Summary of Key Points A thorough travel and exposure history is key to distinguishing naturally occurring from intentional viral hemorrhagic fever cases. Viral hemorrhagic fevers can be transmitted via exposure to blood and bodily fluids. Dr.T.V.Rao MD 52


Pathogenesis. Enters through the bite of Insect vector, Multiply in RES. Target the organ CNS Encephalitis, Liver Yellow fever, Capillary endothelium in Hemorrhagic fevers. Dr.T.V.Rao MD 53

Rodent Borne Hemorrhagic Fevers,:

Rodent Borne Hemorrhagic Fevers , Hanta Virus, Produces pulmonary infections in USA Belong to Bunya Virus –Hanta Viruses Dr.T.V.Rao MD 54

Hanta Viruses,:

Hanta Viruses, Human disease Hemorrhagic fever with renal syndrome Hanta virus pulmonary syndrome. Spread by inhalation of Aerosols of Rodent Excreta, Renal Involvement and failure Lead to Hemorrhagic shock, Korea Spread by Rats carried in ships, Dr.T.V.Rao MD 55

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Dr.T.V.Rao MD 56

Laboratory Diagnosis:

Laboratory Diagnosis Detection of viral nucleic acid, Grown in culture lines, PCR, Dr.T.V.Rao MD 57

Filoviruses, African Hemorrhagic Fevers.:

Filoviruses, African Hemorrhagic Fevers. Most important Diseases are Marburg and Ebola. The nature of Viruses are 80 nm Filamentous threads, Produce Internal and external Bleeding. Dr.T.V.Rao MD 58

Filoviruses. Marburg :

Filoviruses. Marburg Marburg 1967 African Green Monkey, Bat – Rodent – Host Human. East Africa Monkey – Humans. Dr.T.V.Rao MD 59

Filoviruses - Ebola:

Filoviruses - Ebola Incubation 2-21 days Carries 80% mortality. Barrier Nursing Most essential. ELISA test Culturing Hazardous. RT-PCR Transporting and carrying Primates is Hazardous Dr.T.V.Rao MD 60

PowerPoint Presentation:

1979, 2004 1994 1994, 1996, 1996 1976, 1995 1996* 2000 1976, 1979, 2004 *Doctor returning from Gabon Ebola Outbreaks Congo 2003 Dr.T.V.Rao MD 61

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Dr.T.V.Rao MD 62

Bunya viruses:

Bunya viruses Rift Valley fever Crimean Congo hemorrhagic fever Dr.T.V.Rao MD 63

Rift Valley Fever:

Rift Valley Fever Disease of sheep and cattle Humans: Asymptomatic-to-mild Rare VHF, encephalitis, retinit is

Rift Valley Fever:

Rift Valley Fever Mosquito-borne ( Aedes spp . ) vertical transmission in mosquitos Transmission: Animal contact (birthing or blood) Laboratory aerosol Mortality 1% overall Therapy: Ribavirin? Live-attenuated vaccine (MP-12) undergoing trials Dr.T.V.Rao MD 65

Rift Valley Fever: Clinical features:

Rift Valley Fever: Clinical features 3-7 day incubation, 3-5 day duration Asymptomatic or mild illness Fever, myalgia, weakness, weightloss Photophobia, conjunctivitis Encephalitis <5% hemorrhagic fever 1-10% vision loss (retinal hemorrhage, vasculitis ) Dr.T.V.Rao MD 66


CRIMEAN CONGO HEMORRHAGIC FEVER (CCHF) Extensive geographic distribution (Africa, Balkans, and western Asia) Transmission: Tick-borne ( Hyalomma spp.) Contact with animal blood or products Person-to-person transmission by contact with infectious body fluids Laboratory worker transmission documented Mortality 15-40% Therapy: Ribavirin Dr.T.V.Rao MD 67

CCHF: Pathogenesis:

CCHF: Pathogenesis Viremia present throughout disease IFA becomes positive in patients destined to survive days 4-6, often simultaneously with viremia Recovery may be due to CMI or neutralizing antibodies Patients that die usually still viremic Virus grows in macrophages and other cells DIC often present Poor prognosis signaled by early elevated AST and clotting Dr.T.V.Rao MD 68

CCHF: Clinical features:

CCHF: Clinical features 4-12 day incubation after tick exposure 2-7day incubation after direct contact with infected fluids Abrupt onset fever, chills, myalgia, severe headache Malaise, GI symptoms, anorexia Leukopenia, thrombocytopenia, hemoconcentration, proteinuria, elevated AST Hemorrhages may be profuse (hematomas, ecchymoses) Dr.T.V.Rao MD 69


PREVENTION OF CCHF DEET repellents for skin Permethrin repellents for clothing – (0.5% permethrin should be applied to clothing ONLY) Check for and remove ticks at least twice daily. If a tick attaches, do not injure or rupture the tick. Remove ticks by grasping mouthparts at the skin surface using forceps and apply steady traction. Dr.T.V.Rao MD 70

Guanarito (Venezuelan Hemorrhagic Fever):

Guanarito (Venezuelan Hemorrhagic Fever) Venezuela, central plains Rodent borne ( Zygodontomys brevicauda ) Person-to-person transmission not documented Mortality 20-30% Therapy: Ribavirin(?) Dr.T.V.Rao MD 71

South American Hemorrhagic Fevers: Clinical features:

South American Hemorrhagic Fevers: Clinical features 1-2 week incubation Gradual onset fever, malaise, myalgias, anorexia Headache, abdominal pain, nausea, vomiting, orthostasis Petechiae (axillae, palate), gingival hemorrhage Neurologic signs (hyporeflexia, tremor, lethargy, hyperesthesia) Leukopenia, thrombocytopenia, proteinuria Dr.T.V.Rao MD 72

South American Hemorrhagic Fevers: Clinical features:

South American Hemorrhagic Fevers: Clinical features 70% Recovery in 7-8 days without sequelae , prolonged fatigue and weakness common. Severe disease Severe hemorrhage Delerium , coma, convulsions Combined hemorrhagic/neurologic disease High mortality Dr.T.V.Rao MD 73

PowerPoint Presentation:

Rule out or treat febrile illnesses: malaria, rickettsia, leptospirosis, typhoid, dysentery Early hospitalization Distant medical evacuation associated with high mortality Cautious sedation and analgesia Careful hydration Pressors , cardiotonic drugs Support of coagulation system VHF: Supportive therapy Dr.T.V.Rao MD 74


Ribavirin Guanosine nucleoside analog: blocks viral replication by inhibiting IMP dehydrogenase Licensed for treatment of RSV and HCV Potential adverse effects: Dose dependent reversible anemia Pancreatitis Teratogen in rodents Dr.T.V.Rao MD 75

Ribavirin: toxicities:

Ribavirin: toxicities Teratogenic Extravascular hemolysis Bone marrow suppression Rigors with abrupt iv administration Reversible hyperbilirubinemia , hyperuricemia with oral administration Pruritus, nausea, depression, cough Dr.T.V.Rao MD 76

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Programme Created By Dr.T.V.Rao MD for Medical and Paramedical Students in Developing World Email [email protected] Dr.T.V.Rao MD 77

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