Arboviruses:

(AR-thropod Bo-rne Viruses)

Definitive

hostArthropod

Both Hosts become infected

Some viruses very specific in host-vector relationship

Some very generalist

A. Cyclopropagative Transmission: The parasite undergoes cyclical changes and multiplies within the vector, i.e., there are both developmental changes and multiplication of the parasite.

B. Cyclodevelopmental Transmission: The parasite undergoes cyclical changes within the vector but does not multiply, i.e., there are only developmental changes of the parasite without multiplication.

C. Propagative Transmission: The parasite multiplies within the vector without any cyclical changes, i.e., the parasite increases in number within the vector but does not undergo any developmental changes.

Transmission by Insect vectors

Insect ingested (double pored tapeworm)

1) As insect bloodfeeds, parasites in the salivary glands injected into the host along with the saliva (Plasmodium, Arboviruses).

2) As insect bloodfeeds, parasites in the mouthparts recognize the host as suitable and forcibly exit the mouthparts and enter the host (filarial nematodes).

3) As insect feeds in engorges and defecates, parasites in feces enter host (Chagas disease)

4) As insect feeds it regurgitates compounds from its crop and the parasites enter the host (Plague bacterium)

5) Parasites in 3 and 4 remain in the GI tract and do not come in contact with the tissues that are important in the invertebrate immune response to these parasites.

Arboviruses: Not a taxonomic grouping- many families of viruses included

Epidemiologically related, not phylogenetically related

Why study arboviruses

1) Human health

2) Wildlife health

3) Spread wildlife-humans/domestic animals

Arboviruses

• Infect two physiologically different hosts:– invertebrate vector – persistent infections; few

cytopathic effects– vertebrate host – high titred infections and

massive cytopathic effects.

• Arboviruses cause no measurable detrimental effects on insect vectors

Yellow Fever

Exists in Tropical areas – Central America- in primates

Vectors traditionally are insects of the genus Hemogogus

Mosquitoes feed on primates in treetops- cycle- no problem.

If virus enters spider monkeys- can be lethal=indication of problem

Humans enter picture- but we do not spend significant periods in the treetops

So how does it enter humans?

Yellow fever is a mosquito-borne infection characterized by hepatic, renal, and myocardial injury, bleeding, and a high case-fatality rate. The disease occurs in tropical South America and sub-Saharan Africa. Maintained by zoonotic transmission between sylvatic mosquitoes and nonhuman primates, the virus cannot be eradicated, and prevention of human infection requires high vaccination coverage.

Recently the incidence of yellow fever has increased dramatically. The true incidence is believed to far exceed the reported incidence. Yellow fever remains a public health problem because of failure to implement effective immunization, particularly in Africa.

The recent upsurge in yellow fever activity has been associated with an increased risk for infection among non-immunized travelers. In 1996, two tourists infected in the Amazon region of Brazil died after returning home. Fatal and other cases in tourists were also reported in previous years. Other cases were likely missed, misdiagnosed as viral hepatitis, treated abroad, or not reported.

Symptoms: incubation period of three to six days. There are then two disease phases. While some infections have no symptoms whatsoever, the first, "acute", phase is normally characterized by fever, muscle pain (with prominent backache), headache, shivers, loss of appetite, nausea and/or vomiting.

After three to four days most patients improve and their symptoms disappear.However, 15% enter a "toxic phase" within 24 hours. Fever reappears and several body systems are affected. The patient rapidly develops jaundice and complains of abdominal pain with vomiting. Bleeding can occur from the mouth, nose, eyes and/or stomach. Once this happens, blood appears in the vomit and faeces. Kidney function deteriorates; this can range from abnormal protein levels in the urine to complete kidney failure with no urine production. Half of the patients in the "toxic phase" die within 10-14 days. The remainder recover without significant organ damage.

Yellow fever is difficult to recognize, especially during the early stages. It can easily be confused with malaria, typhoid, rickettsial diseases, haemorrhagic viral fevers (e.g. Lassa), arboviral infections (e.g. dengue), leptospirosis, viral hepatitis and poisoning (e.g. carbon tetrachloride).

Sylvatic (or jungle) yellow fever: In tropical rainforests, yellow fever occurs in monkeys that are infected by wild mosquitoes. The infected monkeys can then pass the virus onto other mosquitoes that feed on them. These infected wild mosquitoes bite humans entering the forest resulting in sporadic cases of yellow fever. The majority of cases are young men working in the forest (logging, etc). On occasion, the virus spreads beyond the affected individual.

Intermediate yellow fever: In humid or semi-humid savannahs of Africa, small-scale epidemics occur. These behave differently from urban epidemics; many separate villages in an area suffer cases simultaneously, but fewer people die from infection. Semi-domestic mosquitoes bite both monkey and human hosts. This area is often called the "zone of emergence", where increased contact between man and infected mosquito leads to disease. This is the most common type of outbreak seen in recent decades in Africa. It can shift to a more severe urban-type epidemic if the infection is carried into a suitable environment (with the presence of domestic mosquitoes and unvaccinated humans).

Urban yellow fever: Large epidemics can occur when migrants introduce the virus into areas with high human population density. Domestic mosquitoes (of one species, Aedes aegypti) carry the virus from person to person; no monkeys are involved in transmission. These outbreaks tend to spread outwards from one source to cover a wide area.

Humans cut down forest- increase contact between humans/Hemogogus

Vectors brought into contact with humans

Infected primates brought into contact with other insects including Aedes aegypti

Aedes aegypti loves humans

In the 60’s eradication programs were started to eradicate Ae. aegypti

Very successful- now returned to many areas

Jungle cycle: transmission in primates/few humans by Hemogogus/ Ae. aegypti

Urban cycle: humans and Ae. aegypti

Once cases show up- health authorities enter with vaccines

Yellow fever outbreak reported in ParaguayHealth officials reported an outbreak of yellow fever in Paraguay, with seven confirmed cases in San Pedro and four as yet unconfirmed cases in San Lorenzo.

In addition, the number of cases reported by neighboring Brazilian health authorities has more than quadrupled during the past two months, with 13 deaths reported.

Yellow fever is a viral disease transmitted by mosquitoes. Although a vaccine exists, there is no cure for the disease that infects about 200,000 people annually. "As with malaria, the yellow fever outbreaks highlight the urgent need for carefully controlled insecticide spraying programs," said Richard Tren, director of Africa Fighting Malaria. "These programs should have been strengthened to sustain progress.

"Decades of anti-insecticides pressure culminated in 1997 when the World Health Assembly passed a resolution to reduce the use of insecticides in disease control," added Tren. "The resurgence of yellow fever is an unfortunate consequence of that resolution.“ The World Health Organization said it has sent 4 million doses of vaccine to Paraguay, along with an epidemiologist, virologist and other emergency management experts.

Yellow Fever Trivia

In 1793, yellow fever ravaged Philadelphia, killing 10% of its residents.

The British lost 20,000 of 27,000 in 1741 in Mexico, French lost 29,0000 of 33,000 trying to acquire Haiti and Mississippi valley

Yellow fever killed 20,000 people in New Orleans and Mississippi in 1853, and another 20,000 there in 1878, when the epidemic ran as far north as Memphis.

May have led France to negotiate to give up the Louisiana Purchase

Yellow fever and malaria forced France to abandon completion of the Panama canal, William Gorgas developed mosquito control program in Cuba- copied in Panama

In the 20th century, US and Canada vanquished malaria and yellow fever with a combination of quarantine, medicine, hygiene, and chemical pesticides. DDT made the biggest difference.

But the mosquito always returns, often carrying new diseases.

• Geographically wide spread arbovirus• 2.5 billion people at risk• 50-100 million new infections annually• ~500,000 cases of DHF• No vaccine, no drugs

Arboviruses: Dengue virus

Dengue and dengue hemorrhagic fever (DHF) are caused by one of four closely related, but antigenically distinct, virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4). Infection with one of these serotypes does not provide cross-protective immunity, so persons living in a dengue-endemic area can have four dengue infections during their lifetimes.

Dengue is primarily a disease of the tropics, and the viruses that cause it are maintained in a cycle that involves humans and Aedes aegypti, a domestic, day-biting mosquito that prefers to feed on humans. Infection with dengue viruses produces a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal hemorrhagic disease. Important risk factors for DHF include the strain and serotype of the infecting virus, as well as the age, immune status, and genetic predisposition of the patient.

Dengue is the most important mosquito-transmitted viral disease in terms of morbidity and mortality. Dengue fever is a benign acute febrile syndrome occurring in tropical regions. In a small proportion of cases, the virus causes increased vascular permeability that leads to a bleeding or disseminated intravascular coagulation (DIC) known as dengue hemorrhagic fever (DHF). In 20-30% of DHF cases, the patient develops shock, known as the dengue shock syndrome (DSS).

The global distribution of Dengue is comparable to that of malaria, and an estimated 2.5 billion people live in areas at risk for epidemic transmission. Each year, tens of millions of cases of dengue fever occur and, depending on the year, up to hundreds of thousands of cases of DHF.

The emergence of dengue/DHF as a major public health problem has been most dramatic in the American region. In an effort to prevent urban yellow fever, the Pan American Health Organization eradicated Ae. aegypti from most Central and South American countries in the 1950s and 1960s.

Epidemic dengue occurred only sporadically in some Caribbean islands during this period. The Ae. aegypti eradication program gradually eroded and this species began to reinfest countries from which it had been eradicated. In 1997, the geographic distribution of Ae. aegypti was wider than its distribution before the eradication program

PHNOM PENH, 15 January 2008 (IRIN) - Cambodia could be facing another severe dengue fever outbreak, according to health workers.

“If not this year, then next year - it will certainly come,” warned the leading dengue fever specialist with the World Health Organisation (WHO) in Cambodia, Chang Moh Seng. “It’s only a matter of time.” Last year 407 people died of dengue fever, which is caused by a mosquito-transmitted virus, and nearly 40,000 cases were reported during 2007. “This was the most serious dengue epidemic I have experienced in nearly 30 years of working in the area,” Chang told IRIN. “And the death rate in Cambodia’s outbreak of reported cases was extraordinarily high,” he said. Health education regarding the prevention, diagnosis, and treatment of dengue fever is insufficient, under-funded, and irregular,” according to a 2007 study -

HANOI, Vietnam - Dengue fever is raging across Asia, prompting the World Health Organization to warn that the region could face the worst outbreak of the mosquito-borne virus in nearly a decade.

The disease, commonly called the ’bone breaker’ illness because of the excruciating joint pain it causes, has flared everywhere from ultramodern Singapore to poor Vietnam. There are four different types of dengue, but none have a cure or vaccine.

Cambodia is now one of the most worrisome spots, where the disease has attacked about 25,000 people and killed nearly 300 children this year. That’s about three times more than the number of cases for all of 2005, according to WHO.

                                                           The incidence of dengue fever in rose by 15% in the last two weeks, with a total of 90,000 cases and 99 deaths from the disease so far this year.

90,360 cases have been reported thus far in 2010, a jump from the 78000, and 93 deaths reported two weeks ago.

A state of emergency has been declared in the Colombian city of Cali (Cali, 500 m above sea level). At least 1,247 dengue cases have been found in Cauca, and 162 of the victims are in a serious condition.

Colombia

Costa Rica: Dengue Fever Outbreak

Dengue fever is increasing in Costa Rica and has claimed its first victim in more than six years.

A 24-year-old man died in Puntarenas Aug. 20. More than 14,000 cases of dengue fever have been reported since January, an increase of 35 percent over last year.

The central Pacific and Atlantic regions are the most affected, with Guanacaste, Limon and Puntarenas being high-risk areas.

The mosquito that carries dengue fever bites during the day, so protect yourself day and night. Onset of the fever can occur up to two weeks after being infected.

The reasons for this dramatic global emergence of dengue/DHF as a major public health problem are complex and not well understood. However, several important factors can be identified:

1) First, effective mosquito control is virtually nonexistent in many countries.

2) Major global demographic changes have occurred: uncontrolled urbanization and concurrent population growth. These demographic changes have resulted in substandard housing and inadequate water, sewer, and waste management systems, all of which increase Ae. aegypti population densities and facilitate transmission of Ae. aegypti-borne disease.

3) Third, increased travel by airplane provides the ideal mechanism for transporting dengue viruses between population centers of the tropics, resulting in a constant exchange of dengue viruses and other pathogens.

4) Lastly, in most countries the public health infrastructure has deteriorated. Limited financial and human resources and competing priorities have resulted in a "crisis mentality" with emphasis on implementing so-called emergency control methods in response to epidemics rather than on developing programs to prevent epidemic transmission.

Dengue

Transmitted by Mosquitoes (Aedes aegypti, Aedes albopictus)

Four serotypes

Dengue fever normal in first episode

DSS, DHF possible after second/third exposures

No vaccine………WHY NOT?

No drugs………...Why NOT?

Dengue intervention strategies:

Mathematical model

Cost of Dengue

Cost of intervention

Who does intervention?

Who pays for it?

Who benefits?

When should Dengue control be done

Control?

1) Kill mosquito

2) Do not let mosquitoes bite

3) Drugs

4) Vaccines: they exist. Why are they not available?

Chikungunya Outbreak 2014

Chikungunya is a viral disease first found in Tanzania in 1952

Symptoms similar to dengue virus

As of January 2015: 34 countries infected in the Americas mostly in the Caribbean, now moving to South America

>1,200,000 suspected and 24,000 confirmed chikungunya cases were reported

How did it get to the Americas?

a) Uncertainty in climate change projections: IPCC 1996: T = 1.0 to 3.5oC by 2100IPCC 2001: T = 1.4 to 5.8oC

b) Nonlinear response: mean temperature insufficient to make accurate predictions

c) Evolution: pathogens and vectors likely to adapt physiologically and genetically

Challenges for Modeling Effects of Climate Change on Vectors and Parasites /

Pathogens