Arboviruses

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Arthropod-Borne Arthropod-Borne DiseasesDiseases

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ARTHROPOD - BORNE ARTHROPOD - BORNE DISEASESDISEASES

Malaria - Anopheles mosquito

Yellow fever - Aedes mosquito

Dengue fever - Aedes mosquito

Encephalitis - Aedes/Culex/fleas

Epidemic typhus - Body louse

Bubonic plague - flea

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Arthropod-borne Viruses

Arthropod-borne viruses (arboviruses) are viruses that can be transmitted to man by arthropod vectors. 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 venereal transmission in arthropods.”

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. Flaviviruses e.g. Yellow Fever, dengue, Japanese Encephalitis

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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.

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Man-Arthropod-Man Cycle

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Animal-Arthropod-Man Cycle

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Arthropod Vectors

MosquitoesJapanese encephalitis, dengue, yellow fever, St. Louis encephalitis, EEE, WEE, VEE etc.

TicksCrimean-Congo haemorrhagic fever, various tick-borne encephalitides etc.

Examples of Arthropod Vectors

Aedes AegytiAssorted Ticks

Anopheles Culex Mosquito

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TICKS THAT TRANSMIT LYME TO MAN

Deer Tick Pacific Black-legged Tick

Photo by John VanDyk, Iowa State Univ.

Dime

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ACTIVE/BIOLOGICAL ACTIVE/BIOLOGICAL TRANSMISSIONTRANSMISSION

Inoculation Regurgitation Fecal contamination Contamination from crushing vector

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Animal Reservoirs

In many cases, the actual reservoir is not known. The following animals are implicated as reservoirs

Birds Japanese encephalitis, St Louis encephalitis,

EEE, WEE

Pigs Japanese encephalitis

Monkeys Yellow Fever

Rodents VEE, Russian Spring-Summer encephalitis

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Diseases Caused

Fever and rash - this is usually a non-specific illness resembling a number of other viral illnesses such as influenza, rubella, and enterovirus infections. The patients may go on to develop encephalitis or haemorrhagic fever.

Encephalitis - e.g. EEE, WEE, St Louis encephalitis, Japanese encephalitis.

Haemorrhagic fever - e.g. yellow fever, dengue, Crimean-Congo haemorrhagic fever.

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Diagnosis

Serology - usually used to make a diagnosis of arbovirus infections.

Culture - a number of cell lines may be used, including mosquito cell lines. However, it is rarely carried out since many of the pathogens are group 3 or 4 pathogens.

Direct detection tests - e.g detection of antigen and nucleic acids are available but again there are safety issues.

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Prevention

Surveillance - of disease and vector populations

Control of vector - pesticides, elimination of breeding grounds

Personal protection - screening of houses, bed nets, insect repellants

Vaccination - available for a number of arboviral infections e.g. Yellow fever, Japanese encephalitis, Russian tick-borne encephalitis

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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 inapparent 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. Since Culex has a flight range of 20km, all local control measures will

fail. An effective vaccine is available.

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Yellow Fever (1)

Flavivirus, mainly found in West Africa and S America

Yellow fever occurs in 2 major forms: urban and jungle (sylvatic) yellow fever. Jungle YF is the natural reservoir of the disease in a cycle involving nonhuman primates and forest mosquitoes. Man may

become incidentally infected on venturing into jungle areas. The urban form is transmitted between humans by the Aedes aegypti

mosquito

Classically Yellow Fever presents with chills, fever, and headache. Generalized myalgias and GI complaints (N+V).

Some patients may experience an asymptomatic infection or a mild undifferentiated febrile illness.

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Yellow Fever (2)

After a period of 3 to 4 days, the more severely ill patients with a classical YF course will develop bradycardia (Faget's sign), jaundice, and haemorrhagic manifestations.

50% of patients with frank YF will develop fatal disease characterized by severe haemorrhagic manifestations, oliguria and hypotension.

Diagnosis is usually made by serology There is no specific antiviral treatment An effective live attenuated vaccine is available against yellow

fever and is used for persons living in or traveling to endemic areas.

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Dengue (1)

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

Classically, dengue presents with a high fever, lymphadenopathy, myalgia, bone and joint pains, headache, and a maculopapular rash.

Severe cases may present with haemorrhagic fever and shock with a mortality of 5-10%. (Dengue haemorrhagic fever or Dengue shock syndrome.)

Distribution of Dengue

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Dengue (2)

Dengue haemorrhagic fever and shock syndrome appear most often in patients previously infected by a different serotype of dengue, thus suggesting an immunopathological mechanism.

Diagnosis is made by serology. No specific antiviral therapy is available. Prevention of dengue in endemic areas depends on mosquito

eradication. The population should remove all containers from their premises which may serve as vessels for egg deposition.

A live attenuated vaccine is being tried in Thailand with encouraging results.

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Lyme disease is caused by the bacterium BorreliaBorrelia

burgdorferi . burgdorferi .

LYME DISEASELYME DISEASE - TRANSMISSION OF LYME DISEASE TO MAN

Lyme is transmitted from the reservoir species to man primarily by the nymph stage of the the ticktick.

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TRANSMISSION OF LYME DISEASE TO MAN

The tick waits on a blade of grass or leaf of a shrub with its front legs extended. It crawls onto the potential host when it brushes against the extended front legs.

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COMMON EARLY SYMPTOMS

Fever Head Ache Fatigue Muscle Pain Rash

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COMMON EARLY SYMPTOMS

Bulls Eye Rash: Erythema Migrans

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CHRONIC SYMPTOMS

Joint Pain Arthritis Facial paralysis

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Rickettsia Clinical significance – the diseases caused by

Rickettsia are all characterized by fever, headache, myalgias, and usually a rash.

• Typhus fevers – incubation is 5-18 days. Symptoms include a severe headache, chills, fever, and after a fourth day, a maculopapular rash caused by subcutaneous hemorrhaging as Rickettsia invade the blood vessels. The rash begins on the upper trunk and spread to involve the whole body except the face, palms of the hands, and the soles of the feet. The disease lasts about 2 weeks and the patient may have a prolonged convalescence. Two types of typhus may occur:

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Rickettsia• Epidemic typhus – caused by R. prowazekii

and transmitted by human licehuman lice as it bites and defecates in the wound. This occurs in crowded areas causing epidemics. Mortality rates are high in untreated cases. Following an initial attack, some individuals may harbor the organism of a latent infection with occasional relapses = Brill-Zinsser disease

• Endemic typhus – caused by R. typhi and transmitted to man by rat fleasrat fleas. The disease occurs sporadically, but is clinically the same, but less severe than epidemic typhus.

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INSECTICIDES.

Insecticides are agents of chemical or biological origin that control insects. Control may result from killing the insect or otherwise preventing it from engaging in behaviors deemed destructive. Insecticides may be natural or manmade and are applied to target pests in a myriad of formulations and delivery systems (sprays, baits, slow-release diffusion, etc.). The science of biotechnology has, in recent years, even incorporated bacterial genes coding for insecticidal proteins into various crop plants that deal death to unsuspecting pests that feed on them.

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ORGANOCHLORINESORGANOCHLORINES

The organochlorines are insecticides that contain carbon (thus organo-), hydrogen, and chlorine. They are also known by other names: chlorinated hydrocarbons, chlorinated organics, chlorinated insecticides, and chlorinated synthetics. The organochlorines are now primarily of historic interest, since few survive in today’s arsenal.

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Diphenyl AliphaticsDiphenyl Aliphatics--The oldest group of the organochlorines is the diphenyl aliphatics, which included DDT, DDD, dicofol, ethylan, chlorobenzilate, and methoxychlor. DDT is probably the best known and most notorious chemical of the 20th century. It is also fascinating, and remains to be acknowledged as the most useful insecticide developed. More than 4 billion pounds of DDT were used throughout the world, beginning in 1940, and in the U.S. ending essentially in 1973, when the U.S. Environmental Protection Agency canceled all uses. The remaining First World countries rapidly followed suit. DDT is still effectively used for malaria control in several third world countries. In 1948, Dr. Paul Muller, a Swiss entomologist, was awarded the Nobel Prize in Medicine for his lifesaving discovery of DDT (1939) as an insecticide useful in the control of malaria, yellow fever and many other insect-vectored diseases.

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Hexchlorocyclohexane (HCHHexchlorocyclohexane (HCH)--Also known as benzenehexachloride (BHCbenzenehexachloride (BHC), the insecticidal properties of HCH were discovered in 1940 by French and British entomologists. In its technical grade, there are five isomers, alpha, beta, gamma, delta and epsilon. Surprisingly, only the gamma isomer has insecticidal properties. Consequently, the gamma isomer was isolated in manufacture and sold as the odorless insecticide lindane. In contrast, technical grade HCH has a strong musty odor and flavor, which can be imparted to treated crops and animal products. Because of its very low cost, HCH is still used in many developing countries. In 2002, the U.S. EPA removed all food-related (tolerance-requiring) uses of lindane from the U.S.

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ORGANOPHOSPHATESORGANOPHOSPHATES

Organophosphates (OPs)Organophosphates (OPs) is the term that includes all insecticides containing phosphorus. Other names used, but no longer in vogue, are organic phosphates, phosphorus insecticides, nerve gas relatives, and phosphoric acid esters. All organophosphates are derived from one of the phosphorus acids, and as a class are generally the most toxic of all pesticides to vertebrates. Because of the similarity of OP chemical structures to the "nerve gases," their modes of action are also similar. Their insecticidal qualities were first observed in Germany during World War II in the study of the extremely toxic OP nerve gases sarin, soman, and tabun. Initially, the discovery was made in search of substitutes for nicotine, which was heavily used as an insecticide but in short supply in Germany.

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CARBAMATESCARBAMATES

The carbamate insecticides are derivatives of carbamic acid (as the OPs are derivatives of phosphoric acid). And like the OPs, their mode of action is that of inhibiting the vital enzyme cholinesterase (ChE).

The first successful carbamate insecticide, carbaryl (Sevin®), was introduced in 1956. More of it has been used worldwide than all the remaining carbamates combined. Two distinct qualities have made it the most popular carbamate: its very low mammalian oral and dermal toxicity and an exceptionally broad spectrum of insect control. Other long-standing carbamate insecticides are methomyl (Lannate®), carbofuran (Furadan®), aldicarb (Temik®), oxamyl (Vydate®), thiodicarb (Larvin®), methiocarb (Mesurol®), propoxur (Baygon®), bendiocarb (Ficam®), carbosulfan (Advantage®), aldoxycarb (Standak®), promecarb (Carbamult®), and fenoxycarb (Logic®, Torus®

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PYRETHROIDSPYRETHROIDS

Natural pyrethrum has seldom been used for agricultural purposes because of its cost and instability in sunlight. In recent decades, many synthetic pyrethrin-like materials have become available. They were originally referred to as synthetic pyrethroids. Currently, the better nomenclature is simply pyrethroids. These are stable in sunlight and are generally effective against most agricultural insect pests when used at the very low rates of 0.01 to 0.1 pound per acre.

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The first generation contains only one pyrethroid, allethrin (Pynamin®), which appeared in 1949

The second generation includes tetramethrin (Neo-Pynamin®) (1965), followed by resmethrin (Synthrin®) in 1967 (20X as effective as pyrethrum), then bioresmethrin (50X as effective as pyrethrum) (1967), then Bioallethrin® (1969), and finally phonothrin (Sumithrin®) (1973).

The third generation includes fenvalerate (Pydrin® [discontinued], Tribute®, & Bellmark®), and permethrin (Ambush®, Astro®, Dragnet®, Flee®, Pounce®, Prelude®, Talcord®& Torpedo®) which appeared in 1972-73.

Recent additions to the fourth generation pyrethroids are acrinathrin (Rufast®), imiprothrin (Pralle®), registered in 1998, and gamma-cyhalothrim (Pytech®), which is in development.

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FUMIGANTSFUMIGANTS

The fumigants are small, volatile, organic molecules that become gases at temperatures above 40oF. They are usually heavier than air and commonly contain one or more of the halogens (Cl, Br, or F). Most are highly penetrating, reaching through large masses of material. They are used to kill insects, insect eggs, nematodes, and certain microorganisms in buildings, warehouses, grain elevators, soils, and greenhouses and in packaged products such as dried fruits, beans, grain, and breakfast cereals.

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INSECT REPELLENTSINSECT REPELLENTS

Historically, repellents have included smoke, plants hung in dwellings or rubbed on the skin as the fresh plant or its brews, oils, pitches, tars, and various earths applied to the body. Before a more edified approach to insect olfaction and behavior was developed, it was wrongly assumed that if a substance was repugnant to humans it would likewise be repellent to annoying insects.

In recent history, the repellents have been dimethyl phthalate, Indalone®, Rutgers 612®, dibutyl phthalate, various MGK® repellents, benzyl benzoate, the military clothing repellent (N-butyl acetanilide), dimethyl carbate (Dimelone®) and diethyl toluamide (DEET, Delphene®). Of these, only DEET has survived, and is used worldwide for biting flies and mosquitoes. Most of the others have lost their registrations and are no longer available.