Arbo viral disease

ARBO VIRAL DISEASES  Arthropod  It -borne & transmitted is a collective name for a large group of diverse viruses. replicates in arthropods & vertebrate hosts  Mosquitoes, ticks, sandflies Humans, monkeys, kangaroo, birds, rabbits  Virus 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 transovarian and possibly veneral transmission in arthropods‖. Arboviruses belong to families 1. Togaviridae – Alpha virus (Mosquito-borne) Eastern Equine Encephalitis Western Equine Encephalitis Venezuelan Equine Encephalitis 2. Bunyaviridae – Bunya virus California encephalitis virus 3. Flaviviridae – Flavi virus St. Louis encephalitis Yellow Fever virus Dengue virus West Nile virus 4. Reoviridae – Orbivirus Colorado tick fever virus Family & Genus I. TogaviridaeAlphavirus (Mosquito-borne) Encephalitis WEE, EEE, VEE Febrile illness •Chickengunya •O’nyong-nyong •Semliki forest •Sindbis •Ross river virus Haemorrhagic fever • Chickengunya II. FlaviridaeFlavivirus i) Mosquito-borne • St. Louis encephalitis • Ilheus •West Nile • Murray Valley encephalitis • Japanese B encephalitis • Dengue, types 1-4 • Dengue • Yellow fever ii) Tick-borne • Russian spring summer encephalitis • Powassan • Kyasanur Forest disease • Omsk Haemorrhagic fever III. Bunyaviridae a) Bunya virus (Mosquito-borne) b) Phlebovirus (Phlebotomus or mosquito-borne) c) Nairovirus (tick-borne) • California encephalitis • La Crossie • Chittor virus •Sandfly fever •Rift –valley fever •Nairobi sheep disease •Ganjam virus Family & Genus Encephalitis Febrile illness Haemorrhagic fever IV. Reoviridae Orbivirus (Tick - borne) V. Rhabdoviridae Vesiculovirus (Mosquito-borne sandfly-borne) • Colorado tick borne virus • Vesicular stomatitis virus • Chandipura virus Properties: Togaviridae: virus contains icosahedral nucleocapsid surrounded by an envelope and a single stranded RNA genome. Flaviviridae: Similar to toga but are smaller in size. Bunyaviridae: Have helical nucleocapsid surrounded by an envelope and a genome consisting of three segments of RNA that are hydrogen – bonded together. All the members share common biological properties: 1. 2. 3. 4. 5. Produces fatal encephalitis in suckling mice after intracerebral inoculation They possess hemagglutinin and agglutinate erythrocytes of goose or day old chick Mosquito borne arbovirus multiply in Aedes and Culex mosquito while tick borne in Ixodid ticks They can be grown in tissue culture of primary cellschick embryo fibroblasts or continuous cell lines like vero. They are readily inactivated at room temperature and bile salt, ether.  These viruses are spread by haematophagous arthropod vectors (blood sucking insects). vectors include mosquitoes and biting flies. Arboviruses are vector specific and will replicate only in their specific host. virus is usually transmitted to the vector by a blood meal and replicates in the vector eventually making its way to the salivary glands where it can be transmitted to a second animal upon feeding. Thus the virus is amplified by the vector.  These  The  The vector is usually infected for life and does not display any signs of sickness due to viral replication. winter months in cold climates the vector numbers decrease or the vector disappears. arbovirus infections tend to be epidemic and seasonal based on the presence of a large number of infected vectors during warmer months.  During  Thus  The virus has mechanism for overwintering: this may involvetransovarial transmission (adult female to egg) or reintroduction of virus by infected migratory birds. many arboviruses vector transmission can also occurSexually or trans-stadially (larva to nymph to adult).  For  Most arboviruses exist in enzootic cycles (natural cycles) of transmission in which virus is transmitted by insect vectors from bird to bird or among small mammals. the vector should feed on a human or equine the virus may be transmitted (epizootic infection) with illness resulting. Equines and humans are usually dead end hosts.  If Transmission Cycles  Man - arthropod -man   e.g. dengue, urban yellow fever. Reservoir may be in either man or arthropod vector.  In the latter transovarial transmission may take place.  Animal - arthropod vector - man  e.g. Japanese encephalitis, EEE, WEE, jungle yellow fever.  The reservoir is in an animal.  The virus is maintained in nature in a transmission cycle involving the arthropod vector and animal. Man becomes infected incidentally.  Both cycles may be seen with some arboviruses such as yellow fever. ARBOVIRUS TRANSMISSION CYCLE  A mosquito (vector) picks up a virus (WNV or EEE) from a bird (reservoir), and can either cycle that virus through the bird population (amplification) or transmit the virus directly to a host such as horses and humans (incidental infection). Incubation period: Extrinsic incubation period is the time when the virus multiplies to sufficient amount for the saliva of the vector to contain enough virus to transmit infection. It ranges from 7-14 days. Humans are dead end hosts, because the concentration of virus in human blood is too low and the duration of viremia too brief for the next bite to transmit the virus. In some diseases humans have high level viremia and act as reservoirs of the virus. e.g. yellow fever, dengue. Clinical findings & Epidemiology: The arboviral disease occur primarily in the tropics but are also found in the temperate zones such as US. Arboviral infections can manifest as three types of illnesses in humans. These are  Acute central nervous system disease including aseptic meningitis, encephalitis and encephalomyelitis   Undifferentiated febrile illness with or without rash, and Haemorrhagic fever, a systemic febrile illness with haemorrhagic manifestations, cardiovascular instability and varying degrees of hepatic and renal insufficiency. Pathogenesis Following the arthropod bite Virus replicates locally then spreads to regional lymph nodes It gets disseminated via the lymphatic system into the bloodstream (primary viraemia). The primary viraemia seeds target organs which replicate virus and serve as a source of virus for release into the circulation. Virus can then enter the neural tissue causing encephalitis. Symptoms  The symptoms of arbovirus infection usually have an abrupt onset. With constitutional symptoms occurring firstFever, chills, headache, generalized aches and malaise  Followed in some cases by more severe symptoms of encephalitis- drowsiness, nuchal rigidity, confusion, convulsions, tremors, coma, death or  Haemorrhage (yellow fever and dengue [rare]).  The incubation period can vary from 3 to 21 days. of encephalitis can be severe.  Most arbovirus infections are inapparent and immunity is lifelong.  Sequelae Generalized arbovirus disease cycle Eastern Equine Encephalitis virus: Belongs to genus Alpha virus. It causes the most severe disease and is associated with the highest fatality rate – 50%. Eastern USA, Central & South America. Birds/mosquitoes. Severe CNS disease in horses and man. Incubation: 3 - 7 days Salivary gland of mosquito showing EEE virus Pathogenesis: EEE virus enters the bloodstream via the saliva of an infected female mosquito. Viral replication then occurs in the monocytes leading to the viremic phase of infection. The virus can also infect the capillary endothelial cells to enter the CNS. This leads to neuronal necrosis with neuronophagia (phagocytosis of nerve cells). Risk Factors  Exposure to mosquito bites,  Living near or visiting a wetland area or an area known to have incidents of EEE.  Age is also a risk factor. People over age 50 or under 15 seem to be more susceptible to the infection. Symptoms  Fatigue  Fever  Headache  Nausea  Restlessness or irritability  Difficulty walking or unstableness  Confusion, impaired judgment, or an altered mental state  Seizures  Arthropod Transmission EEE virus is transmitted from birds to mosquitoes to humans and horses If the patient survives the CNS sequelae are severe including mental retardation, epilepsy, paralysis, deafness, and blindness.. Diagnosis  Ask about the patients symptoms and medical history, and perform a physical exam.  Following tests can be asked for:  Blood tests to find out if the virus is present  A spinal tap to remove a small amount of spinal fluid to check for signs of infection  An electroencephalogram (EEG) to measure the brain’s activity A neurological exam to access reflexes, memory, and other brain function  CT scan—a type of x-ray that uses computers to make pictures of structures inside the head  MRI scan—a test that uses magnetic waves to make pictures of structures inside the head Lab Diagnosis: Isolation of virus Demonstration of rise in antibody titer. Treatment: No antiviral therapy available. Medical treatment focuses on treating the symptoms of the infection. Such treatments may include:  Antibiotics to treat secondary infections  Anticonvulsants to treat seizures  A respirator to help with breathing  Pain relievers to treat headache, fever, and body aches  Corticosteroids to reduce swelling in the brain  Sedatives for restlessness or irritability Killed vaccine available for horses but not humans. Prevention  To help reduce your chances of getting EEE, take the following steps:  Avoid areas of mosquito activity, if possible.  Stay inside when mosquitoes are most active (at dawn and at dusk).  When outside, wear insect repellent, long pants and long-sleeved shirts to limit exposure to bites.  To help limit mosquito populations in and around your home, eliminate the insects’ breeding areas. Those may include standing water such as pet water bowls, rain barrels, and other containers. Western Equine Encephalitis: North & South America. Birds/mosquitoes. Severe disease in horses. Milder disease in man. In US the number of cases ranges between 5-20 per year, & fatality rate is 20%. Virus is transmitted primarily by Culex mosquitoes among the wild bird population in areas with irrigated farmland. Risk factors  Living in or visiting the plains regions of the western and central United States outdoors  Working  Participating in outdoor activities Signs & symptoms: Headache Fever Drowsiness Irritability Nausea Vomiting Confusion Weakness Coma Seizures (in young infants) Western Equine Encephalitis Sequelae is less common Diagnosis: is done by isolation of the virus demonstration of rise in antibody titer. Treatment: No antiviral therapy. Treatment will focus on managing your symptoms and related complications. Vaccine for horses available. Prevention :  Stay inside between dusk and dark, when mosquitoes are most active.  Wear long pants and long-sleeved shirts when outside.  Spray exposed skin with an insect repellent that contains up to 35% diethyltoluamide (DEET). St. Louis Encephalitis virus (SLE): Wider geographic area then the EEE & WEE. Found in southern central and western states of US. 10-30 cases per year. The virus is spread by several species of Culex mosquito. Reservoirs: small wild birds – english sparrows. SLE seen in urban areas because these mosquitoes breed in the stagnant water. Fatality rate is 10% . Sequelae is not common. Risk Factors: Some factors thought to increase the risk of St. Louis encephalitis include:  Elderly  Living age in or visiting the southern, central, or western United States, especially during the summer and fall Symptoms Headache Fever Neck stiffness Stupor Disorientation Coma Tremors Convulsions (especially in infants) Paralysis  Diagnosis : Serological diagnosis is done. Treatment: No antiviral therapy. Prevention  Stay inside between dusk and dark. This is when mosquitoes are most active.  Wear long pants and long-sleeved shirts when outside.  Spray exposed skin with an insect repellent that contains up to 35% diethyltoluamide (DEET). California Encephalitis (CE) virus: Was first isolated from mosquitoes in California in 1952. La Crosse virus - California serogroup virus It belongs to family Bunyaviridae It is the most common arboviral cause of encephalitis in US. Approximately 70 cases reported per year TRANSMISSION  Virus cycles in woodland habitats between the treehole mosquito (Aedes triseriatus) and vertebrate hosts (chipmunks, squirrels)  Virus survives winter in mosquito  Vector uses artificial containers (tires, buckets, etc.) in addition to treeholes RISK GROUPS  Children <16 years old: biological risk factor  Residence in woodland habitats environmental risk factor  Containers at residence environmental risk factor  Outdoor activities: behavioral risk factor Clinical picture can be mild, resembling enteroviral meningitis or severe resembling herpes encephalitis. Diagnosis: made serologically. No antiviral therapy or vaccine available. Colorado tick fever (CTF)virus: It is a Reovirus. Transmitted by wood tick – Dermacentor andersoni Among small rodents e.g. chipmunks and squirrels. Geographic range is confined to the western US states and areas above 5,000 ft. in elevation 100-300 cases per year is seen in US. Symptoms • High fever • Chills • Severe headache • Pain behind the eyes • Sensitivity to light • Muscle pain • Lethargy • Abdominal pain • Vomiting • Nausea Complications are extremely rare and include aseptic meningitis, encephalitis, and hemorrhagic fever. Diagnosis: isolation of the virus detecting a rise in antibody titer. Prevention:  Avoid tick-infested areas, especially during warmer months.  Wear light-colored clothing to better locate a crawling tick.  Tuck pants into socks when in tick-infested habitats.  Use tick repellents.  Regularly inspect and remove ticks from your body and your child’s body when in tick-infested habitats.  Remove ticks using fine-tipped tweezers by grasping the tick close to the skin’s surface and pulling upward steadily.  Disinfect tick bites with soap and water. West Nile virus (WNV): Asia, Central and South Africa (Transvaal). Birds and mosquitoes. Human outbreaks usually after rains. Out break of encephalitis in New York in the month of July, Aug & Sept. 1999 was seen with 27 were confirmed cases. 2000 there were 18 cases 2001 48 cases were seen & 5 deaths. It not known how the virus entered US, may be through infected person or an infected bird. Reservoirs: wild birds Transmitted by mosquitoes (Culex species). Humans are dead end hosts. Clinical symptoms: Fever, confusion and striking muscle weakness similar to Guillain – Barr syndrome. Laboratory diagnosis: Isolation of the virus from brain tissue, blood, or spinal fluid. Detection of antibodies in spinal fluid or blood PCR is also available Treatment: No antiviral therapy or vaccine available. Important arbovirus that cause disease outside the US Yellow fever virus: The infection is characterized by jaundice and fever. It is severe, life threatening disease. Two distinct cycles exist in nature with different reservoirs and vectors. 1. Jungle yellow fever – disease of monkeys in tropical Africa and South America. Vectors: tree top mosquitoes – Haemagogus spp. Reservoirs- monkeys humans are accidental hosts. 2. Urban yellow fever is a disease of humans. Vectors: mosquito Aedes aegypti , breeding in the stagnant Water. Reservoirs: Humans Intrinsic incubation period is 3-6 days. YellowFever (YF) Africa: Central, West East. Central South America (Amazon basin). Hosts: Monkey mosquito (=silent reservoir). Jungle (sylvan) YF sporadic cases in forest worker/visitor. Urban )YF YF introduced into towns; now get cycle: man - mosquito - man. NB. Mosquito control is important. Illness: as above, but jaundice is a prominent feature (liver necrosis). Vaccine: i) "17 D strain" live attenuated virus Good safe long lasting protection but labile and expensive to administer. Used in the RSA. ii) "French Dakar Vaccine" live attenuated brain tissue-derived vaccine Inoculated by skin scratch. More stable and cheap to administer. Occasionally causes CNS complications. Widely used in Froncophone Africa. Vaccination is required for travel to endemic zones (or rather, for return to non-endemic zones!) Risk Factors  The following factors increase your chance of getting yellow fever:  Living, working, or traveling in jungle or urban areas with yellow fever, including:  Sub-Saharan Africa  33 countries in Africa have constant cases of yellow fever  South America  Bolivia, Brazil, Colombia, Ecuador, and Peru provide greatest risk  Failure to take proper precautions. Precautions include the following:  Receiving the yellow fever vaccination  Reducing contact with mosquitoes (for example, using bed nets, long-sleeved clothing, and screens)  Using insect repellents   Symptoms  Yellow fever has two phases: acute and toxic. All individuals infected with yellow fever will experience the acute phase. Fifteen percent of people with yellow fever will progress into the toxic phase. Acute Phase • Fever • Headache • Muscle pain • Backache • Chills • Loss of appetite • Nausea and/or vomiting Toxic Phase  High fever  Abdominal pain  Bleeding from the gums, nose, eyes, and/or stomach  ―Black‖ vomit (vomit that appears black due to blood content)  Low blood pressure  Liver failure, which may lead to jaundice (yellowing of the skin and whites of the eyes)  Kidney failure  Confusion  Seizure  Coma  Death (approximately 50% of toxic phase patients die) Diagnosis: Isolation of the virus Detecting a rise in antibody titer. Prevention: Mosquito control Vaccine: vaccine containing live, attenuated virus available. Travelers to and residents of endemic areas should be immunized. Protection lasts for 10 yrs. Booster dose is required every 10 yrs. Vaccine:  i) "17 D strain" live attenuated virus Good safe long lasting protection but labile and expensive to administer.  ii) "French Dakar Vaccine" live attenuated brain tissuederived vaccine Inoculated by skin scratch. More stable and cheap to administer. Occasionally causes CNS complications.  Vaccination is required for travel to endemic zones (or rather, for return to non-endemic zones!) Dengue virus: (Break Bone Fever) The first reported epidemics of DF occurred in 1779-1780 in Asia, Africa, and North America. It belongs to Flavi virus group. It is not endemic in US some tourists return with this disease. 100-200 cases per year seen in US mostly in southern and eastern states. About 20 million people get infected each year worldwide. Vector : Aedes aegypti Serotypes: virus serotypes DEN-1, DEN-2, DEN-3, and DEN-4 Risk Factors  Travel to tropical or subtropical areas, such as:  Africa  India  Southeast Asia and China  Middle East  Countries in the Caribbean and Central and South America  Australia  Locations in the Central and South Pacific Symptoms Classic dengue begins suddenly with an influenza like syndrome       Fever Malaise Cough Headache Severe pain in the muscle and joints Enlarged lymphnode, maculopapular rash and leukopenia are common. This typical form is rarely fatal. Dengue hemorrhagic fever: Fatality rate 10% Initial picture is same as the classic dengue fever Later shock and hemorrhage, especially into the gastrointestinal tract and skin develop. Dengue hamorrhagic fever occurs in southern Asia, Hemorrhagic shock syndrome is due to production of large amounts of cross reacting antibody at the time of second dengue infection Lab diagnosis: Isolation of virus Demonstarte the prescence of IgM antibody or a 4 fold or greater rise in antibody titer in acute and convalescent stage. Treatment: No antiviral therapy or vaccine. Outbreaks are controlled by using insecticides and draining stagnant water . Personal protection – use of mosquito repellent.  Which one of the following is not an arbovirus? A. Ross River virus B. Murray Valley encephalitis virus C. Barmah Forest virus D. Human papillomavirus * E. Dengue virus REFERENCES LEVINSON 7TH EDITION: CHAPTER 42