Diseases without borders

Aug. 1, 2010
CONTINUING EDUCATION

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LEARNING OBJECTIVES

Upon completion of this article, the
reader will be able to:

  1. Describe characteristics of and identify modes of transmission for leishmaniasis, chagas, dengue, and chikungunya diseases.
  2. Identify diagnosis and treatment protocols for leishmaniasis, chagas, dengue, and chikungunya diseases.

Handle exotic diseases with this lab pocket guide

Globalization made the world a smaller place in a short time. Nowhere is that more evident than in a hospital laboratory in the United States that discovers an exotic disease has been introduced into its environs. The ingress of leishmaniasis into America, courtesy of Desert Storm several years ago, is one example among several that have sometimes confounded healthcare specialists. Here, learn about what to look for in the event one of these five exotic diseases show up on your lab’s doorstep.

Leishmaniasis
Description: Leishmaniasis (pronounced LEASH-ma-NIGH-a-sis) is an ancient parasitic disease found in parts of the tropics, subtropics, and southern Europe. The disease received considerable attention in 2003 during the U.S. invasion of Iraq, when hundreds of soldiers began to find red bumps on their skin that swelled for weeks before rupturing into seeping wounds. The number of cases dropped to a handful a month by last year, but the threat remains as long as U.S. troops are stationed in Iraq and Afghanistan.1

September 2003 was one of the highest months of leishmaniasis infection among U.S. troops in the past seven years; and, at that time, the Defense Department issued a memorandum asking healthcare personnel to “increase their level of suspicion for this disease among redeploying personnel from Afghanistan, Iraq, and other areas where leishmaniasis is endemic and sand flies are prevalent.”

When an infected sand fly bites a human, it injects the parasite under the skin, explains the chief of the Infectious Diseases Service at Walter Reed Army Medical Center: “They multiply, they burst out of that macrophage [white blood cell], infect other macrophages, and there is a progressive infection, eventually causing an ulcer in the skin. Ironically, the parasite stays alive by hiding inside the human body’s center of immunity: white blood cells.1

Soldiers were required to apply a DEET-based product to their bodies and to treat their uniforms with a repellent called permethrin. The director of the Leishmania Diagnostics Laboratory at the Walter Reed Army Institute of Research in Silver Spring says those rules, along with having more soldiers sleeping in buildings rather than in tents, reduced the number of infections.1

Military medical personnel initially were much more vigorous in searching out, diagnosing, and reporting cases than they are now because, in 2003, they did not know which strain of leishmania parasites they were battling. Since that time, they have learned that the vast majority of the parasites in Iraq are leishmania major, a type that is not as dangerous as strains found in other regions of the world.1

Transmission: The disease is caused by infection with Leishmania parasites, which are spread by the bite of infected sand flies.2 which breed in forest areas, caves, or the burrows of small rodents.3 Rarely, leishmaniasis is spread from a pregnant woman to her baby, and can be spread by blood transfusions or contaminated needles.4

Diagnosis: The most common forms of leishmaniasis in people are 1) cutaneous leishmaniasis, which causes skin sores, and 2) visceral leishmaniasis, which affects some of the internal organs of the body (e.g., spleen, liver, and bone marrow).2 In cutaneous forms, skin ulcers usually form on exposed areas, such as the face, arms, and legs but usually heal within a few months. Although the ulcers heal spontaneously, they can cause serious disability and leave severe and permanent disfiguring scars. Discrimination, stigma, and substandard living conditions are associated with cutaneous leishmaniasis; epidemics are especially devastating in refugee camps.3

Diffuse cutaneous leishmaniasis produces disseminated and chronic skin lesions resembling those of lepromatous leprosy and is difficult to treat. In mucocutaneous forms, the lesions can partially or totally destroy the mucous membranes of the nose, mouth, throat cavities, and surrounding tissues. Visceral leishmaniasis, also known as kala azar (meaning “black fever” or “deadly sickness” in Assamese, the easternmost Indo-Aryan language), is characterized by high fever, substantial weight loss, swelling of the spleen and liver, and anemia; if untreated, the disease can have a fatality rate as high as 100% within two years.3

According to the World Health Organization (WHO), co-infection with visceral leishmaniasis and HIV is becoming an ominous global trend. In persons infected with HIV, leishmaniasis accelerates the onset of AIDS by cumulative immunosuppression and by stimulating replication of the virus. Due to co-infection, visceral leishmaniasis is no longer restricted to endemic areas; and the number of cases of visceral leishmaniasis and HIV co-infection will continue to rise. In southern Europe, for example, up to 70% of adult cases of visceral leishmaniasis are associated with HIV infection. In some areas of Ethiopia, 35% of all leishmaniasis patients are co-infected with HIV, and the trend is spreading to neighboring countries such as Sudan.3

Leishmaniasis facts

In the world: An estimated 12 million people currently infected; up to 350 million people at risk.3

In the UNITED STATES: Almost all of the people in the United States who have leishmaniasis became infected while traveling or living in other countries. Rare cases of cutaneous leishmaniasis have been reported in Texas and Oklahoma.2

In the news: The June 22, 2010, Washington Post article “Sand flies infect U.S. forces with parasite that leaves them with ‘Baghdad Boil'” highlighted the severity and scope of leishmaniasis. Considered endemic in 88 countries, leishmaniasis is most prevalent in Afghanistan, Brazil, Bangladesh, India, Nepal, Sudan, Bolivia, Peru, Saudi Arabia, and Syria. Leishmaniasis received considerable attention in 2003 during the U.S. invasion of Iraq, after hundreds of American soldiers became infected. As U.S. troops make their way into Afghanistan, doctors and military personnel are warning that the number of cases could rise since the disease is more common in Afghanistan than in Iraq.1

Treatment: Almost as traumatizing as the disease itself is the medication — Pentostam — that is commonly recommended by doctors and which is administered in multiple-injection doses over a period of several weeks. According to the chief of the Infectious Diseases Service at Walter Reed Army Medical Center, the medication is “associated with a tremendous number of side effects.”1 Most patients who use Pentostam are plagued for months by an aggravated pancreas and liver, as well as severe muscle and joint pains, he explains. It is not approved by the Food and Drug Administration: U.S. military patients can get the drug only at Walter Reed, and civilians must obtain it through the Centers for Disease Control and Prevention (CDC).1 Other methods used to get rid of “Baghdad Boil” include a pill called fluconazole, sold under the name Diflucan, which is normally used for fungal infections. For leishmaniasis, it is taken once a day for six weeks but is not nearly as effective as Pentostam, he claims.1 Liposomal amphotericin B is available as a highly effective treatment for visceral leishmaniasis, with a cure rate surpassing 90%.The cost, distribution and storage requirements, and administration of this life-saving medicine, however, are factors that have restricted wider access.5

Chagas disease
Description:
Chagas disease is named after the Brazilian physician Carlos Ribeiro Justiniano Chagas, who discovered the disease in 1909. Chagas disease (Trypanosoma cruzi infection) is also referred to as American trypanosomiasis.6 Chagas disease is endemic throughout Mexico, and Central and South America, and is caused by the protozoan parasite T cruzi, which is transmitted to humans by blood-sucking insects of the family Reduviidae (Triatominae). Although mainly a vector-borne disease, Chagas disease can be acquired by humans through blood transfusions and organ transplantation, congenitally (from a pregnant woman to her baby), and through oral contamination (e.g., foodborne).6 Originally (>9,000 years ago), T cruzi only affected wild animals but later spread to domestic animals and people. The large reservoir of T cruzi parasites in wild animals of the Americas means that the parasite cannot be eradicated. Instead, the control targets are elimination of the transmission and healthcare access for the infected and ill population. 6

Transmission: Chagas disease was once entirely confined to the region of the Americas — principally Latin America — but has now spread to other areas,6 including the U.S. and Europe, carried by unsuspecting immigrants in their blood.8 The disease is transmitted to humans through the feces of triatomine bugs, known as ‘kissing bugs.’6 These bugs typically live in the cracks of poorly-constructed homes in rural or in suburban areas. Normally, they hide during the day and become active at night when they feed on human blood. They usually bite an exposed area of skin such as the face, and the bug defecates close to the bite. Parasites enter the body when the person instinctively smears the bug feces into the bite, the eyes, the mouth, or into any skin break.6

Diagnosis: Chagas disease presents itself in two phases. The initial, acute phase lasts for about two months after infection. During the acute phase, a high number of parasites circulate in the blood. In most cases, symptoms are absent or mild but can include fever, headache, enlarged lymph glands, pallor, muscle pain, difficulty in breathing, swelling, and abdominal or chest pain. In less than 50% of people bitten by a triatomine bug, characteristic first visible signs can be a skin lesion or a purplish swelling of the lids of one eye.

During the chronic phase, the parasites are hidden mainly in the heart and digestive muscle. Up to 30% of patients suffer from cardiac disorders and up to 10% suffer from digestive (typically enlargement of the esophagus or colon), neurological, or mixed alterations. In later years, the infection can lead to sudden death or heart failure caused by progressive destruction of the heart muscle. In some cases, it can cause an acute form of meningitis or swelling of the brain.8

With Chagas disease, its symptoms can lie dormant for years before it is diagnosed. Many of the problems causing the spread of Chagas can be related to the difficulties of diagnosing the disease, says a molecular biologist from Merida, who is developing an instrument that he believes could dramatically decrease the prevalence of diseases such as Chagas.8 The machine is a cheap, portable “DNA Xerox machine” that he hopes will allow doctors in rural areas to be able to diagnose patients without having to wait for test results from Caracas.8 Up until now the DNA-testing technique the machine uses has not been widely available because of the size and cost of the equipment. The inventor has managed to shrink the size of the machine and hopes to bring the cost down from $3,000 to $300 with each test costing $.25. At that price, he says this portable machine would make it possible to have one of these, if not in every laboratory, at least in every large hospital.8

Treatment: Neither a vaccine against infection nor a completely effective treatment for chronic Chagas disease currently exists.5 A professor emeritus at the Venezuelan Institute of Scientific Research has developed Prosaconazole, a drug that in trials in Spain has proved to be one of the most effective treatments for the chronic stage of Chagas.8

A meaningful response to Chagas requires implementation of screening and treatment programs using available tools (benznidazole and nifurtimox), and dedicated R&D for new diagnostics and treatments as the existing tools require complex and long regimens, and do not have pediatric formulations.1

Chagas facts

In the world: 15 million cases worldwide. As many as 8 million to 11 million people in Mexico, Central America, and South America have Chagas disease.6 More than 108 million people considered at risk.5 Chagas causes an estimated 20,000 deaths worldwide each year.5

In the United States: About 300,000 cases reported.5

In the news: “Venezuela: the hidden Chagas disease,” published June 11, 2010, in the Global Post, reports that the outbreak of Chagas at the Andres Bello College in Chacao in 2007 is one of three major Chagas outbreaks in Venezuela in the past three years. The latest outbreak was in Caracas, which affected at least 19 people and killed one, indicating that this disease, which was previously believed to be under control, is once again on the rise in Venezuela. Three years ago, some 100 children and teachers at a school in the middle-class Caracas neighborhood of Chacao were infected with Chagas disease after drinking juice at the school canteen.9 The Venezuelan Parasitological Society calculates that cases of Chagas have tripled in the past two decades, from affecting 0.5% of the population to 1.6%. This illness now kills more people in the region than malaria.9

Vector control is the most effective method of preventing Chagas disease, as well as other diseases transmitted by insects. Blood screening is necessary to prevent Chagas infection through transfusion and organ transplantation.6

In keeping with the goal of eliminating Chagas disease by 2010, the WHO Global Network for Chagas Elimination developed a five-pillar strategy before the end of 2007. The efforts to eliminate Chagas disease are enhanced by the pharmaceutical industry which is providing financial support to the network, along with donations of a drug known to be effective for the treatment of the disease.7

Dengue
Description:
While Floridians have spent weeks in angst over the Gulf of Mexico oil spill, they probably were unaware the Dengue fever, an infectious disease, had come to vacation in Key West. Dengue (pronounced “DENG-ee”) is caused by any of four related viruses transmitted to humans by the bite of infective female mosquitoes Aedes albopictus (nicknamed “Asian tiger mosquito”) and Aedes aegypti. First seen in the United States in 1985, Ae albopictus has been found in 36 states, while Ae aegypti has been found in several southern states. Experience elsewhere in the world shows that where these mosquitoes go, the disease usually follows.10 The disease used to be called “break-bone” fever because it sometimes causes severe joint and muscle pain that feels like bones are breaking.11

Health experts have known about dengue fever for more than 200 years.11 The severe forms of dengue disease have been defined by the WHO as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS).13 Dengue fever is found mostly during and shortly after the rainy season in tropical and subtropical areas of Africa, Southeast Asia and China, India, Middle East, Caribbean, Central and South America, Australia, and the South and Central Pacific. An epidemic in Hawaii in 2001 is a reminder that many locations in the United States are susceptible to dengue epidemics because they harbor the particular types of mosquitoes that transmit dengue virus.11

In addition to typical dengue, DHF and DSS also have increased in many parts of the world.11 DHF, a potentially lethal complication, was first recognized in the 1950s during dengue epidemics in the Philippines and Thailand.14 A disease most Americans have never heard of could soon become more prevalent if dengue, a flu-like illness that can turn deadly, continues to expand into temperate climates and increase in severity.10 Previously confined to tropical and subtropical climates, the mosquito-borne illness is becoming a much more serious problem along the U.S.-Mexico border and in the commonwealth of Puerto Rico. Dengue occurs sporadically and has had a relatively small impact on the United States, thus far. The amount of dengue-related illness in this country is presently minimal; however, the disease tends to occur in explosive epidemics.10

Transmission: The only way to prevent dengue-virus transmission is to combat the disease-carrying mosquitoes.14 Mosquitoes generally acquire the virus while feeding on the blood of an infected person. After virus incubation for eight to 10 days, an infected mosquito is capable, during probing and blood feeding, of transmitting the virus for the rest of its life. Infected female mosquitoes may also transmit the virus to their offspring by transovarial (via the eggs) transmission, but the role of this in sustaining transmission of the virus to humans has not yet been defined.

Infected humans are the main carriers and multipliers of the virus, serving as a source of the virus for uninfected mosquitoes. The virus circulates in the blood of infected humans for two to seven days; at approximately the same time that they have a fever; Aedes mosquitoes may acquire the virus when they feed on an infected individual during this period. Some studies have shown that monkeys in some parts of the world play a similar role in transmission.14

Recovery from infection by one of the four viruses provides lifelong immunity against that virus but confers only partial and transient protection against subsequent infection by the other three viruses. There is good evidence that sequential infection increases the risk of developing DHF.14

Diagnosis: Most people infected with a dengue virus have no symptoms or a mild fever. Those who do get sick sometimes experience minor bleeding, such as from the nose or gums, and frequently develop a high fever, severe headache, pain behind the eyes and in joints and muscles, and a rash. Sometimes, the disease leads to leakage of blood plasma out of the circulatory system and into tissues, causing blood pressure to drop. This condition often can be reversed by giving patients fluids and electrolytes.10

DHF is a potentially deadly complication that is characterized by high fever, often with enlargement of the liver and, in severe cases, circulatory failure. The illness often begins with a sudden rise in temperature accompanied by facial flush and other flu-like symptoms. The fever usually continues for two to seven days and can be as high as 41^0C, possibly with convulsions and other complications.14 In moderate DHF cases, all signs and symptoms abate after the fever subsides. In severe cases, the patient’s condition may suddenly deteriorate after a few days of fever; the temperature drops, followed by signs of circulatory failure, and the patient may rapidly go into a critical state of shock and die within 12 to 24 hours, or quickly recover following appropriate medical treatment.14

Dengue facts

In the world: Dengue is endemic in at least 100 countries in Asia, the Pacific, the Americas, Africa, and the Caribbean. In 2007, there were more than 890,000 reported cases of dengue in the Americas. As many as 100 million people worldwide are infected yearly.10 About 2.5 billion people are at risk.14

In the United States: 100 to 200 cases each year. Dengue outbreaks also have been reported in Hawaii in 2001, in south Texas in 2005, and in south Florida in 2009.12

In the news: Evidence of the dengue virus has been found in 28 people who live in or have visited Key West, FL, according to a CDC report published May 21, 2010. The first case that came to the CDC’s attention was that of a 34-year-old woman who sought medical care for headache, fever, and other symptoms after a one-week Key West visit in August 2009. She was seen three times before she was tested for dengue and found to have antibodies to dengue virus serotype 1 (DENV-1). A 48-year-old Key West man saw his doctor for similar symptoms, including a truncal maculopapular rash. He asked to be tested for dengue, and a private lab identified dengue antibodies in the man’s serum sample, as did another test conducted by the CDC. Meanwhile, a nurse at the county health department learned that the man’s wife had similar symptoms, and the CDC confirmed her dengue diagnosis as well. Since 1980, dengue infections have been sporadically detected near the U.S.-Mexico border, but the CDC says these are the first cases to be diagnosed outside that area since 1945 and Florida’s first since 1934.12

Treatment: Early clinical diagnosis and careful clinical management by experienced physicians and nurses increase survival of DHF patients. There are no specific antiviral medicines for dengue. It is important to maintain hydration. Use of acetylsalicylic acid (e.g., aspirin) and non steroidal anti-inflammatory drugs (e.g., Ibuprofen) is not recommended.13 Early diagnosis and treatment of dengue are critical to preventing shock and death.12 With proper treatment, case fatality rates for severe dengue can be less than 1%. If left untreated, however, the person may become unresponsive, slip into a coma, and, possibly, die.12

Although progress is underway, developing a vaccine against the disease — in either its mild or severe form — is challenging. With four closely related viruses that can cause the disease, the vaccine must immunize against all four types to be effective.14 While there is limited understanding of how the disease typically behaves and how the virus interacts with the immune system and while there is a lack of laboratory animal models available to test immune responses to potential vaccines,13 two vaccine candidates have advanced to evaluation in human subjects in countries with endemic disease, and several potential vaccines are in earlier stages of development. WHO provides technical advice and guidance to countries and private partners to support vaccine research and evaluation.14

Chikungunya
Description:
Chikungunya reputedly gets its name from either a Swahili word meaning “that which bends up” or a Makonde word meaning “to become contorted.” In either language, the name refers to a disease symptom: painful joint inflammation resulting in stooped posture.18 The best example of an “old world” alphavirus is Chikungunya virus. It is found in areas of Africa and Asia, especially jungle areas.

Transmission: The primary vector is Aedes aegypti, which can also transmit dengue and yellow fevers. Though Aedes aegypti originated in Africa, it is now found in tropical areas worldwide. An outbreak on the French Indian Ocean island of Reunion in early 2005 infected a quarter of the population in less than two years, causing some 250 deaths. It is rampant today in India, Thailand, and other parts of southeast Asia.17

There are three possible modes of transmission:

  • sporadic cases arise when man comes in contact with jungle areas where the reservoir is in monkeys;
  • prevalent where people-to-people spread occurs by mosquitoes, like in Thailand; and
  • during the rainy season in India when the population of mosquitoes increases greatly and epidemics can occur.16

Authorities fear the virus could be spread globally because it can also be carried by the Asian Tiger mosquito, Ae albopictus, which is found in Asia, Africa, Europe, the Americas, Australia, and New Zealand. This latter species is thought to have been introduced to North America when imported in a shipment of used tires at the port of Houston, TX, in 1985.  It has since spread into the southern regions of the U.S. east of the Mississippi but has been found as far to the north as Maine and Minnesota.  It was also found in Hawaii prior to 1986 and is considered an introduced species there as well.17 Chikungunya is believed to be an eventual threat to the Western Hemisphere.

Chikungunya-virus epidemics signal that the risk of importation into new areas by infected travelers is likely. One expert says the virus is “hyper-endemic in the islands of the Indian Ocean,” and “(t)ravel by air will import the infected mosquitoes and humans.”17 Researchers in Florida are particularly concerned about Florida outbreaks because the state has many international visitors, elderly residents, and warm weather conducive to mosquito breeding.18

Diagnosis: Onset of symptoms occurs from two to 12 days following infection, but usually three to seven days.17 “Silent” (asymptomatic) Chikungunya-virus infections do occur, but it is not yet known how this happens. The clinical disease is a flu-like fever of acute onset, in addition to intense headaches, followed by a pharyngitis, maculopapular rash, and arthritis or joint pain, as well as fatigue, nausea, vomiting, and muscle pain. Minor haemorrhagic manifestations are occasionally seen.16 The disease can be fatal to the elderly, young children, and people with weak immune systems.18 Some patients experience incapacitating joint pain, or arthritis, which may last for weeks or months. While 90% of West Nile virus infections are asymptomatic, the overwhelming majority of those infected with the Chikungunya virus are quite sick.16 The diagnosis of infection is usually made by serology.16

Treatment: There is no vaccine or specific antiviral treatment currently available for Chikungunya fever.17 An experimental vaccine provided 100% protection against the mosquito-borne Chikungunya virus in primates and mice, offering hope it will work for humans too, a new study found. Researchers say human trials will start within a year or two, and that the discoveries made could lead to vaccines for diseases stemming from other so-called alphaviruses, such as various deadly strains of equine encephalitis, and the Ross River virus (which is an RNA alphavirus endemic to Australia, Papua New Guinea, and other South Pacific islands).17

Chikungunya facts

In the world: Chikungunya, first seen in the 1950s, has spread to nearly 20 countries and infected millions.16

In the United States: More than two dozen cases.17 U.S. residents have been diagnosed with Chikungunya after traveling to countries such as Somalia, Kenya, India, Zimbabwe, and the French island of R’eunion in the Indian Ocean. The virus can be passed from the human bloodstream to feeding mosquitoes, so there is a slight risk that Chikungunya virus could be introduced into local mosquito populations in the U.S.18 Imported shipping containers could introduce disease-carrying mosquitoes into previously non-endemic areas, particularly in tropical or subtropical areas of the United States.17

In the news: On June 8, 2010, the CDC issued an outbreak notice for Chikungunya fever in Asia and the Indian Ocean. In 2009, the Ministry of Health in Malaysia reported more than 4,430 cases of Chikungunya fever; and, as of May 15, 2010, there were an additional 549 reported cases. In 2009, Thailand reported 49,069 cases of Chikungunya fever; and, as of May 26, 2010, there were an additional 946 reported cases. More than 43,000 cases were also reported in Indonesia.19

All of this discovery comes at a time when global travel and trade, along with climate change, are expanding the habitats of the mosquitoes that carry these pathogens. Scientists at the Vaccine Research Center at the U.S. National Institutes of Health in Bethesda, MD, identified the proteins that give rise to chikungunya, thus developing the experimental vaccine. The next step is to figure out how to make the vaccine compatible for human use by adapting that vaccine to a cell line where it could be made and tested in preliminary trials.17 Treatment to relieve the discomfort of fever and aching can include rest, fluids, and medicines such as ibuprofen, naproxen, acetaminophen, or paracetamol. Aspirin should be avoided. Infected persons should stay indoors in areas with screens and/or under mosquito nets so they will be protected from further mosquito exposure during the first few days of the illness and not contribute to the transmission cycle.17

Editor’s note: Read more about exotic diseases (not part of the CE test), including the description, transmission, diagnosis, and treatment of malaria here.


References

  1. Athas E. Sand flies infect U.S. forces with parasite that leaves them with ‘Baghdad Boil.’ http://www.washingtonpost.com/wp-dyn/content/article/2010/06/21/AR2010062104103.html. Published June 22, 2010. Accessed July 12, 2010.
  2. Centers for Disease Control and Prevention. Leishmaniasis. http://www.cdc.gov/ncidod/dpd/parasites/leishmania/default.htm. Accessed July 12, 2010.
  3. World Health Organization. Leishmaniasis. http://www.who.int/topics/leishmaniasis/en/. Accessed July 12, 2010.
  4. Spreads from mother to baby rarely; can be spread by contaminated needles, etc. Leishmania Infection: DPD From www.wrongdiagnosis.com/artic/leishmania_infection_dpd.htm. Accessed July 12, 2010.
  5. Neglected Tropical Diseases. Obama’s Global Health Initiative report on leishmaniasis. http://www.theglobalhealthinitiative.org/documents/report_ntd.pdf. Accessed July 12, 2010.
  6. World Health Organization. Chagas. http://www.who.int/topics/chagas_disease/en/index.html. Accessed July 12, 2010.
  7. Emerging Infectious Diseases. www.cdc.gov/eid. Published March 2010;16 (3). Accessed July 12, 2010.
  8. Pandey V. DNA. http://www.dnaindia.com/india/report_chagas-a-threat-for-travellers-to-latin-america_1399619. Accessed July 12, 2010.
  9. Devereux C. Venezuela: the hidden Chagas disease. http://www.globalpost.com/dispatch/venezuela/100610/chagas-disease. Published June 11, 2010. Accessed July 12, 2010.
  10. Morens DM, Fauci AS. Dengue and hemorrhagic fever: A potential threat to public health in the United States. JAMA DOI:10.1001/jama.299.2.214 (2007). http://www.niaid.nih.gov/news/newsreleases/2008/Pages/dengue.aspx.
  11. NIAID. Dengue. http://www.niaid.nih.gov/topics/denguefever/pages/default.aspx. Accessed July 12, 2010.
  12. Dengue fever discovered in Florida. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5919a1.htm. Accessed July 12, 2010.
  13. Dengue. http://virology-online/viruses/Arboviruses. Accessed July 12, 2010.
  14. World Health Organization. Dengue and dengue haemorrhagic fever. Fact sheet No. 117. March 2009. http://www.who.int/mediacentre/factsheets/fs117/en/index.html. Accessed July 12, 2010.
  15. McKenna M. Experts stress vigilance over emerging, unpredictable diseases. http://www.cidrap.umn.edu/cidrap/content/bt/vhf/news/oct2908emerging.html. Published October 29, 2008. Accessed July 12, 2010.
  16. Chikungunya Virus. http://virology-online.com/viruses/Arboviruses.htm. Accessed July 12, 2010.
  17. Experimental vaccine for chikungunya virus shows great promise. http://www.gulf-times.com. http://naturalunseenhazards.wordpress.com/2009/09/23/chikungunya-fever-yet-another-mosquito-borne-viral-disease-is-coming. Accessed July 12, 2010.
  18. Nordlie T. New mosquito-borne illness may be headed to United States, UF experts say. April 26, 2007. http://news.ifas.ufl.edu/2007/04/26/new-mosquito-borne-illness-may-be-headed-to-united-states-uf-experts-say/#more-1666. Accessed July 12, 2010.
  19. Centers for Disease Control and Prevention. Chikungunya Fever in Asia and the Indian Ocean. Published June 8, 2010. http://wwwnc.cdc.gov/travel/content/outbreak-notice/chikungunya-fever.aspx. Accessed June 28, 2010.

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