Epidemiologists, health experts, and politicians are gravely concerned about global transmission of avian influenza type H5N1 to humans. Efforts are being made to decrease the potential pandemic nature of this virus; however, early identification of symptoms and proper reporting of cases is critical to decrease the potential cases expected with this disease.1 Endemic diseases such as malaria and dengue fever that pervade sub-Saharan Africa, South America, Central America, and Asia have relevance to healthcare providers in the United States because of the increasing number of immigrants settling in this country. The recent SARS outbreak crossed Asia, Europe, and North and South America.2 Though currently dormant, SARS may return and cases could originate in the United States. The seasonal epidemic of WNV is endemic in temperate climates such as Europe and the United States; however, it exists where climates are conducive to the breeding of the mosquito responsible for transmission.3 Because of its flu-like symptoms, those who are infected may not be aware of the cause of the illness.

Influenza pandemics occur three to four times a century.4 Forerunners to the H5N1 avian virus are identified as: H1N1, which was responsible for the Spanish flu epidemic of 1918–1919 that killed more people in 1 year than Black Death in the Middle Ages or AIDS over the past 24 years; H2N2, which was responsible for the Asian flu epidemic of 1957–58; and H3N2, which was responsible for the 1968–69 “Hong Kong Flu.”4 Although avian virus is not new, experts fear the evolved H5N1 avian virus may be as lethal today as it was in the 1918 epidemic. Almost 50 years have elapsed since this last epidemic and the World Health Organization (WHO) has classified the current H5N1 situation as a “Phase 3 Pandemic Alert,” meaning human infection with a new subtype has occurred without human contact or with limited human-to-human spread.5

Influenza epidemiology has identified three types of influenza viruses: A, B, and C.5 Influenza types B and C are found in humans and usually cause mild-to-moderate physical reactions. Influenza A, which has 15 subtypes based on the surface proteins of hemagglutinin and neuraminidase, causes the most serious illness and is responsible for avian influenza pandemics.6 Subtypes include H1N1, H1N2, H5N1, and H3N2. The influenza vaccine administered in the United States has H1N1 and H3N2 components.

Wild birds are the natural host for influenza A and carry the virus in their intestines. The migratory pattern of wild birds contributes to the spread of the virus, transmitting it via excrement or the direct consumption of the infected bird. The evolution of the virus has spread to humans.6 The subtypes of avian influenza A are differentiated by severity of disease: high pathogenic avian influenza and low pathogenic avian influenza.6 Unfortunately, H5N1 is a high pathogenic virus with a mortality rate greater than 55%. Since January 2004, the WHO has identified the presence of the H5N1 virus in 11 countries with 208 laboratory confirmed cases and 115 deaths.7

Although avian influenza A is not common in humans, healthcare providers should recognize the evolution of this virus and that the incidence of infection in humans is increasing. To date, infected individuals have had direct contact with infected poultry; therefore, healthcare providers should be aware of patients who are in contact with imported birds. Presenting symptoms of the H5N1 virus can range from typical flu-like symptoms of fever, sore throat, cough, and myalgia, to more severe symptoms of pneumonia, severe respiratory distress, or encephalitis. The incubation period can be 2 to 10 days.8 The lethality depends on the health of the patient; immunocompromised individuals are at the greatest risk for death.9 Routine assessment for those presenting with flu-like symptoms should include questions referring to occupation and potential exposure during the previous 2 weeks.

Treatment focuses on supportive care and management of each body system. Even with respiratory support and empirical treatment with broad-spectrum antibiotics, methylprednisolone (Medrol), and the neuroaminidase inhibitor oseltamivir (Tamiflu), there was an 80% mortality rate in a report of 10 cases of H5N1 infection in Vietnam.10 Future treatment of H5N1 will focus on antiviral medications for the early treatment of infected individuals and those they have had contact with. Cases in Vietnam and Thailand found resistance to such antiviral medications as amantadine (Symmetrel) and rimantadine (Flumadine).11 The two remaining antivirals—oseltamivir and zanamivir (Relenza Diskhaler)—should be effective against the H5N1 strain; however, a strain of the H5N1 virus has shown resistance to oseltamivir.10 Significant efforts are underway to produce effective vaccines against avian influenza A, but several months are needed to ensure an adequate supply.8

Recommendations for infection control have been established by the Centers for Disease Control and Prevention (CDC) and include standard precautions, respiratory hygiene, and cough etiquette; for hospital employees, the addition of droplet, contact, and airborne precautions, eye protection, and possibly isolation are necessary.12

SARS

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is an often fatal form of pneumonia resulting from acute respiratory distress. It is transmitted through close person-to-person contact within a 3-foot radius. The transmission route is thought to be infected respiratory droplets propelled through the air that reach another's upper respiratory mucous membranes. The virus can also spread after touching a surface or object contaminated with infectious droplets and then touching the mouth, nose, or eyes. It is unknown if the SARS-CoV virus can spread via airborne mechanisms, but this mode of transmission has not been ruled out.13

Clinical manifestations can include a prodrome of fever, fatigue, headache, malaise, and myalgias. These initial symptoms may be followed by a dry cough, shortness of breath and difficulty breathing, diarrhea, sore throat, and rhinorrhea.13,14 Severe acute respiratory syndrome has an incubation period of 2 to 10 days. Early systemic symptoms are followed within 2 to 7 days by dry cough and/or shortness of breath, often without upper respiratory tract symptoms. Radiographically confirmed pneumonia may develop by days 7 to 10. Lymphocytopenia is present in most cases.13

Practitioners should ask patients with nonspecific viral upper respiratory infection symptoms about travel or contact with someone who has traveled to a region with previous SARS transmission (China, Hong Kong, Singapore, Taiwan, Vietnam, and Canada) within the past 10 days. They should also ask about possible risks from occupational environments, such as healthcare workers who have direct patient contact, laboratory workers in contact with live SARS-CoV, or if they have had contact with a person known to have radiologic evidence of pneumonia without an alternative diagnosis within the previous 10 days.15

Inpatient evaluation of suspected SARS patients should include immediate notification of the local health department and detailed patient history and physical examination, including anterior, posterior, and lateral chest X-rays, to determine relative risk of exposure and necessity of inpatient admission.14 Patients with suspected SARS infection should be placed in isolation and on droplet precaution (personnel must wear surgical masks when in the presence of the patient); infected areas should be decontaminated immediately.14 Healthcare workers should wear personal protective equipment including fit-tested N-95 respirator, eye protection, disposable impervious gowns, and gloves when in contact with the infected patient.

Until culture reports confirm diagnosis, initial treatment should include broad-spectrum antibacterial drugs effective against typical bacterial causes of community-acquired pneumonia (respiratory fluoroquinolones [levofloxacin], second- and third-generation cephalosporins), in addition to macrolides such as clarithromycin (Biaxin).16 There is no evidence to support the clinical use of antibiotics once SARS-CoV has been confirmed.16 Other drug therapy options include ribavirin (Copegus) and steroid combinations, SARS-CoV protease inhibitors such as a lopinavir/ritonavir (Kaletra) combination, interferons, and steroid combination. Possible future treatments for SARS-CoV may include viral binding inhibitors, fusion inhibitors, RNA interference treatment, glycyrrhizin, nitric oxide, and niclosamide.16

Vaccine trials for SARS-CoV are in progress at the National Institute of Allergy and Infectious Disease. Current research involves a vaccine with a small piece of DNA from the SARS-CoV, which codes protein in its coat.17

The most recent cases of the SARS-CoV infection were reported in China in April 2004 and resulted from laboratory-acquired infections.13 Since July 2003, SARS has appeared 4 times; 3 of these incidents were attributed to breaches in laboratory safety guidelines. The first reported case of SARS occurred in February 2003 in Asia. The trajectory of the disease tracked to more than 24 countries in North America, South America, Europe, and Asia and included a total of 8,098 cases and 774 mortalities.16 The United States documented eight confirmed cases of SARS during the initial outbreak (laboratory tests, although sensitive and specific, may not reliably detect SARS-CoV at the first onset of symptoms).18

Mosquito-Borne Diseases

Prevention is needed most to combat mosquito-borne diseases. West Nile virus, malaria, and dengue fever are three deadly types of disease carried and transmitted through the bites of mosquitoes. Protection from mosquito bites, control of standing water, and support of public health vector control efforts are the most effective means of prevention. Personal protection from mosquito bites includes the use of screens on windows and air conditioning units, light-colored clothing with long sleeves and pants, use of 24% N, N-diethyl-m-toluamide (N, N-diethyl-3-methylbenzamide [DEET]) for those older than 1 year, avoiding the use of perfume and deodorant, using antimalarial drugs prophylactically for malaria, and remaining indoors during early morning and evening hours. Environmentally safe mosquito larvicides are available for home ponds, as are other measures to control mosquito populations.19

West Nile virus, identified in Uganda in 1937, had infrequent and relatively mild outbreaks until the 1990s when outbreaks became more frequent and severe with neuroinvasive presentations in Romania (1990), Russia (1999), and Israel (2000). In 1999, the first U.S. case was diagnosed in New York City, and the virus spread across the continent by 2004.20 In 2000, a reporting and tracking Web site, ArboNet, was established by the CDC to aid in the documentation of WNV transmission.20

West Nile virus is a single-strand RNA of Flaviviridae flavivirus.21 Birds are a reservoir for the virus; however, the Aedes and Ochlerotatus mosquito species bite infected birds and transmit the virus to human and animal populations.22 To complicate the analysis of WNV transmission, recent investigations of mosquito vectors indicate that at least 58 mosquito species may be involved in transmission.22 Most U.S. cases, whether avian or human, occur during the warmer months.

West Nile virus usually resolves without incident. Several studies have documented that among individuals with seroconversion to WNV, only about 20% will develop symptoms.21 The elderly are quite susceptible to WNV and more likely to develop neuroinvasive symptoms21; WNV infection is rarely reported in children, and children rarely have neuroinvasive symptoms.23 The incubation period for WNV is usually 2 to 14 days but can be as long as 21 days. Typical symptoms include malaise, loss of appetite, nausea, headache, and fever. Diagnosis can be missed if clinicians are not vigilant to the transmission cycles or assessing patients for WNV. In general, diagnosis can be frustrating as immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody tests are the most reliable but take time for a positive result.21 In WNV cases, IgG takes 7 to 14 days to reach a positive result; IgM (MAC-ELISA) takes about 1 to 4 days in 75% of cases and 7 to 8 days for 100% of cases. Immunoglobulin M, however, can persist for as long as 500 days and will be positive if a related infection (dengue fever) or recent yellow fever immunization exists.24

White blood cells are normal or slightly elevated; lymphocytopenia and anemia are sometimes present. Treatment is supportive and there is no evidence that antivirals or steroids affect the infection25; however, three clinical trials are exploring pharmacologic treatments for neuroinvasive WNV because of its high mortality or long-term impairment in the elderly.21 The most common presentation of neuroinvasive WNV is fever (90% of patients); less common findings include asymmetrical weakness, gastrointestinal problems, headache, and acute flaccid paralysis.21 Other findings are similar to those seen in viral encephalitis or meningitis. Immunoglobulin M in cerebral spinal fluid is diagnostic of neuroinvasive WNV. Computed tomography (CT) scans are generally negative, and magnetic resonance images are negative or may show focal neurologic lesions.

Since 1999, WNV has infected 17,000 humans, including 6,690 neuroinvasive WNV cases resulting in 670 deaths.22 Nonhuman disease and seroconversions have been identified in many U.S. birds, domestic chickens, mosquitoes, dogs, squirrels, and alligators.22 Transmission of the disease has been found through blood (screening of blood supply began in 2003), breast milk, and organ transplantion.22 In 2003, the CDC registry identified 74 women who acquired WNV illness while pregnant, resulting in mother-to-child transmission. Infants have experienced hypoglycemia, respiratory instability and hypoxic spells, and symptoms of septicemia.26 The greatest incidence of infection and death in the U.S. have been in California, Michigan, Mississippi, and Louisiana.

Another member of the family of deadly mosquito-borne diseases, malaria, has undergone significant changes in morphology over the past 100 years. Malaria is not the static condition once known to have infected early American settlers, but has evolved into a drug-resistant pathogen, killing 1 million children yearly in endemic countries such as Africa, Southeast Asia, Central and South America.27

Malaria is caused by a parasite transmitted by the Anopheles mosquito and is the only mosquito-borne disease that can be prevented and cured by pharmacologic management. The parasite grows in the bloodstream and can produce symptoms that develop anywhere from 6 to 8 days to several months after infection. In rare cases, the parasites can be transmitted from person to person without passage through a mosquito, such as from mother to child or through transfusion, organ transplantation, or shared needles.28

Malaria is dependant on climatic factors such as temperature (the Plasmodium falciparum [malaria parasite] cannot grow or be transmitted in temperatures lower than 68°F), humidity, and rainfall. Eradication of the disease has been impossible because of the development of dichlorodiphenyltrichloroethane resistance in mosquitoes and drug resistance in humans.29 Drug resistance to the primary modality used to treat malaria, chloroquine, is evident in patients from Asia, Africa, South America, India, Iran, and Afghanistan.30

An average of 1,000 cases of malaria are reported annually to the CDC. According to the CDC, 99% of the 1,092 cases reported in 2001 were imported from Africa (66.9%), the Americas (15%), and Asia (14.5%).31 Many cases of malaria are probably misdiagnosed as flu, viral infection, tuberculosis, typhoid fever, meningitis, WNV, and dengue fever; true incidence is unknown.32 In a study conducted in Ontario, Canada, among international travelers, diagnosis was missed initially in 59% of the cases, and community offices incorrectly identified the species of malaria in 64% of cases causing treatment to be subclinical.33

There are four types of malaria. P. falciparum is the most serious and responsible for the majority of deaths. It causes microvascular sequestration and obstruction in the brain, kidney, and liver, which leads to cerebral malaria, anemia, kidney failure, hypoglycemia, disseminated intravascular coagulation (DIC), and fluid imbalance.28Plasmodium vivax and Plasmodium ovale malaria parasites can sequester or lie dormant in the liver for 45 days to 5 years, reenter the RBCs, and cause a relapse. Plasmodium malariae may cause a relapse after many years, possibly because it lies dormant in the RBCs of the spleen.28 A true recovery only occurs when parasites are totally eliminated from the blood.33 Blood smears are necessary for the definitive diagnosis and specific identification of malaria parasites.33

Symptomology includes paroxysms of chills, fever, and sweating. It often begins with shivers, headache, nausea and vomiting, malaise, and anorexia, followed in a few hours by a high temperature with hot, dry, skin and a rapid, bounding pulse, with possible delirium.32 When the temperature falls, a profuse sweating occurs. The sequence of chills, fever, and sweats lasts approximately 10 hours. The cycle of symptoms coincides with bursting erythrocytes (usually every 2 to 3 days); however, there are cases where the cycle is predicated by 5 to 7 days of high fever.32

Diagnosis in the field is usually made by history and symptomology. There are several costly tests that can be performed: microscopic blood smear assessment to visualize the parasite, the Malaria Rapid Diagnostic Tests, polymerase chain reaction assessment to identify parasite nucleic acids (requires a specialized laboratory), or serology detection for antibodies against malaria parasites (using indirect immunofluorescence or enzyme-linked immunosorbent assay). However, serology does not detect current infection.34

Children are prone to complications and deaths from severe malaria. About 800,000 African children die each year from malaria because they are less likely to have developed functional immunity or have long-standing malnutrition.35 Deaths are caused by an overwhelming parasitemia with the sequestration of parasites occurring in the tiny arteries of the brain, leading to death from cerebral malaria. The signs and symptoms of cerebral malaria are delirium, disorientation, coma, and convulsions; first symptoms appear between 10 to 16 days from the time of infection.34 Even if a child does not die from acute malaria, he may develop a chronic malarial parasitemia that will cause anemia and susceptibility to other infections.35

In pregnant women (especially primigravidas), sequestration of a large amount of parasites occurs in the capillaries of the placenta, usually during the second half of pregnancy. This capillary sequestration causes a fetal nutritional and/or oxygen depletion syndrome leading to possible spontaneous abortion, low-birth weight, or cerebral palsy in the infant.28

The drug to treat all four types of malaria is chloroquine (Aralen); however, chloroquine resistance has led to alternative therapies such as: sulfadoxine-pyrimethamine (Fansidar), amodiaquine, artemisinin, artemether, atovaquone-proguanil (Malarone), mefloquine (Lariam), and quinidine gluconate/sulfate). In developing nations, the cost of full pharmacologic treatment is prohibitive. The neurotoxic, psychiatric, gastrointestinal, integumentary, and cardiovascular adverse effects of most medications can prevent compliance to medical therapies and can potentially create further drug resistance.34

Dengue is recognized as the most significant mosquito-transmitted viral disease in terms of mortality. Dengue fever, also known as the breakbone fever, is characterized by fever, rash, and severe muscle/joint pains. The most severe form, dengue hemorrhagic fever, includes the aforementioned symptoms as well as hemorrhagic fever and shock.36 Those at greatest risk are fragile children and the elderly. The mean fatality rate of dengue hemorrhagic fever is 3% to 5% with treatment; 50% without treatment.36 Though not common in the United States, 100 to 200 cases are reported annually from southwest Texas and portions of the southeast.37 Globally, the number of cases reported is increasing, in part because of nonexistent mosquito control, unreliable and inadequate water supply systems, increased use of nonbiodegradable containers, poor solid waste disposal, increasing air travel, and uncontrolled population growth in urban areas worldwide.38 Immigrants to the United States from endemic countries may arrive with symptoms of dengue. Healthcare providers may work in areas of the U.S. where acquisition of this mosquito-borne disease is possible (Hawaii, southeastern U.S., and Texas); it is imperative clinicians know the symptoms and interventions critical to recovery.

Dengue is transmitted by the Aedes aegypti (worldwide) and the Aedes albopictus (United States, Asia, Latin America, and Caribbean) mosquitoes.38 The infected female mosquito is primarily a domestic, daytime feeder that breeds in pools of water and open sewers, preferring to feed on human blood. The mosquito is most prevalent after the rainy season in tropical and subtropical regions.38

There are four distinct but related serotypes (DEN-1, DEN-2, DEN-3, DEN-4). A person can be infected by more than one type at different times during a lifespan, but only once by the same type because of the development of serotype immunity. Exposure to DEN-2 triggers a chain of immunologic events, unchecked replication of the virus, and massive infection. The infection is caused by a release of vasoconstrictive mediators that lead to increased vascular permeability and hemorrhage evident in dengue hemorrhagic fever and dengue shock syndrome.37

Important clinical manifestations are fever (39.4° C to 41.4° C) and a macular rash lasting 1 to 7 days, followed by decreased fever for 1 to 2 days. A secondary morbilliform—maculopapular generalized rash that spares the palms and soles—occurs within a few days of decreased fever and lasts up to 5 days. Generalized lymphadenopathy with severe bone pain in the legs, joints, and lumbar spine can last several weeks. Infants and small children may have nonspecific febrile illness and rash.37 Differential diagnoses can include multiple viral, bacterial, and rickettsial infections that present with fever, chills, rash, headaches, malaise, and arthralgias. If a fever occurs more than 2 weeks after travel to an endemic area, dengue should be eliminated as a potential diagnosis. Practitioners should ask patients about travel and exposure history, as the major risk factor for developing dengue is living in an endemic region, and development of hemorrhagic fever is greater in an endemic region with more than one serotype.37 Genetic predisposition may also be a factor as African-Americans are at lower risk; immunocompromised individuals are at greater risk for morbidity and mortality.37

Antibody assay and serology testing 2 to 3 weeks apart can identify the presence of infection and serotype. Other diagnostics include complete blood cell count (white blood cell count, platelets, hematocrit, and hemoglobulin), which looks for leucopenia and hemorrhage risk, electrolytes, liver function, urine, and stool guaiac. To establish a diagnosis of dengue hemorrhagic fever, all of the above tests plus hemorrhagic manifestations, decreased platelet count (less then 100,000/mm3), and evidence of leaky capillaries (elevated hematocrit, low albumin, pleural or other effusions (DIC panel, chest X-ray, and CT scan of head to diagnose effusions and bleeding) must exist.38

There is no definitive treatment for dengue fever. The primary goal is supportive therapy to maintain fluid and electrolytes. Oxygen, antipyretics (no aspirin or nonsteroidal anti-inflammatory drugs because of anticoagulant properties), and pain medication may be administered.39 Prevention is crucial to decreasing the incidence of dengue with preventive therapies similar to malaria. In Vietnam, water bugs (Mesocyclops) are being added into the water reservoirs where mosquitoes breed to eliminate the mosquito population.39 Continued research is needed to find effective means of controlling this disease.

Awareness is Key

1. Centers for Disease Control and Prevention. Outbreak notice: Guidelines and recommendations interim guidance about Avian Influenza A (H5N1) for U.S. citizens living abroad. Available at: http://www.cdc.gov/travel/other/avian_flu_ig_americans_abroad_032405.htm . Accessed November 5, 2006. [Context Link]

2. Centers for Disease Control and Prevention. Severe acute respiratory syndrome (SARS): Basic information about SARS. Available at: http://www.cdc.gov/ncidod/sars/factsheet.htm . Accessed November 5, 2006. [Context Link]

3. Centers for Disease Control and Prevention. West Nile Virus: What you need to know. CDC Fact Sheet. Available at: http://www.cdc.gov/ncidod/dvbid/westnile/wnv_factsheet.htm . Accessed November 5, 2006. [Context Link]

4. Centers for Disease Control and Prevention. Information about influenza pandemics. Available at: http://www3.niaid.nih.gov/news/focuson/flu/illustrations/timeline/timeline . Accessed January 4, 2007. [Context Link]

5. Centers for Disease Control and Prevention. Influenza viruses. Available at: http://www.cdc.gov/flu/avian/gen-info/flu-viruses.htm . Accessed January 4, 2007. [Context Link]

6. Centers for Disease Control and Prevention. Key facts about avian influenza (bird flu) and avian influenza A (H5N1) virus. http://www.cdc.gov/flu/avian/gen-info/facts.htm . Accessed January 4, 2007. [Context Link]

7. World Health Organization. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. Available at: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2006_05_12/en/index.html . Accessed November 5, 2006. [Context Link]

8. Centers for Disease Control and Prevention. Avian influenza (bird flu): avian influenza infection in humans. Available at: http://www.cdc.gov/flu/avian/gen-info/avian-flu-humans.htm . Accessed November 5, 2006. [Context Link]

9. Fouchier RA, Schneeberger PM, Rozendaal FW, et al.: Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci USA 2004;101(5):1356–61. [Context Link]

10. Le M, Kiso M, Someya K, et al. Isolation of drug-resistant H5N1 virus. Nature. 2005; Oct 20;437(7062):1108. [Context Link]

11. de Jong M, Van Cam B, Tu Qui P, et al. Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. NEJM. 2005;352(7):686–691. [Context Link]

12. Centers for Disease Control and Prevention. Interim recommendations for infection control in health-care facilities caring for patients with known or suspected avian influenza (under revision). Available at: http://www.cdc.gov/flu/avian/professional/infect-control.htm . Accessed November 5, 2006. [Context Link]

13. Centers for Disease Control and Prevention. Clinical guidance on the identification and evaluation of possible SARS-CoV disease among persons presenting with community-acquired illness: version 2. Available at: http://www.cdc.gov/ncidod/sars/word/clinicalguidance.doc . Accessed November 5, 2006. [Context Link]

14. North Carolina Department of Health and Human Services, Division of Public Health, General Communicable Disease Control. NC SARS Response Plan: Supplement B: SARS Surveillance. Available at: http://www.epi.state.nc.us/epi/gcdc/sars/sars_state_plan_docs/supplementB/supp_B_sarsSurveillance.pdf . Accessed November 5, 2006. [Context Link]

15. Leung GM, Rainer TH, Fei-Lung L, et al. A clinical prediction rule for diagnosing severe acute respiratory syndrome in the emergency department. Ann Intern Med. 2004;141(5):333–342. [Context Link]

16. Groneburg DA, Poutanen DE, Low HL, et al. Treatment and vaccines for severe acute respiratory syndrome. Lancet Infect Dis. 2005;5(3):147–155. [Context Link]

17. Yang Z, Kong W, Huang Y, et al. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature. 2004:428(6982):561–564. [Context Link]

18. World Health Organization, Western Pacific Region. Investigation into China's recent SARS outbreak yields important lessons for global health. July 2, 2004. Available at: http://www.wpro.who.int/sars/docs/update/update_07022004.asp . Accessed November 5, 2006. [Context Link]

19. Centers for Disease Control and Prevention. Fight the bite. Available at: http://www.cdc.gov/ncidod/dvbid/westnile/ . Accessed November 5, 2006. [Context Link]

20. Centers for Disease Control and Prevention: Brownstein JS. Enhancing WNV surveillance, US. Emerging Infectious Diseases. 2004; 10:6 Available at: http://www.cdc.gov/ncidod/dvbid/westnile . Accessed January 4, 2007. [Context Link]

21. Peterson LR, Marfin AA, Gubler DJ. Clinician's corner: West Nile virus. JAMA. 2003;290:524–528. [Context Link]

22. Centers for Disease Control and Prevention. Hayes et al. Virology, Pathology, and Clinical Manifestations of West Nile Virus Disease. Emerging Infectious Diseases. 2005;11:8. Available at: http://www.cdc.gov/ncidod/dvbid/westnile/ . Accessed January 4, 2007. [Context Link]

23. Yim R, Posfay-Barbe KM, Nolt D, et. al. Spectrum of clinical manifestations of West Nile virus infection in children. Pediatrics. 2005;115(5):1445. [Context Link]

24. Centers for Disease Control and Prevention. Roehrig et al. Persistence of virus-reactive serum immunoglobulin M antibody in confirmed West Nile Virus encephalitis cases. Emerging Infectious Diseases. 2003; 9:3. Available at: http://www.cdc.gov/ncidod/dvbid/westnile/ . Accessed January 4, 2007. [Context Link]

25. National Institute of Allergy and Infectious Disease. NIAID Research on West Nile Virus. Available at: http://www.niaid.nih.gov/factsheets/westnile.htm . Accessed January 4, 2006. [Context Link]

26. Klee AL, Maidin B, Edwin B, et al. Long-term prognosis for clinical West Nile virus infection. Emerg Infect Dis. 2004;10(8):1405–1411. [Context Link]

27. Bradley DJ. The last and the next hundred years of malariology. Parassitologia. 1999;41(1–3):11–18. [Context Link]

28. Baer B, Hunter A, Meehan N, et al. A quick reference to malaria treatment. Am J Nurs Prac. 2004. [Context Link]

29. Bjorkman A. Malaria research: back to the future. Parassitologia.1999;41(1–3):505–506. [Context Link]

30. Baird JK, Hoffman SL. Primaquine therapy for malaria. Clin Infec Dis. 2004;(3)9:1336–1345. [Context Link]

31. Pillai D, Kain KC. Malaria update. Infectious Diseases and Microbiology Rounds Feb 2002;2(2). Available at: http://www.idrounds.ca/crus/idmbeng_0202.pdf . Accessed November 5, 2006. [Context Link]

32. Impact Malaria (Sanofi Aventis). Malaria news information and training: malaria symptoms. Available at: http://www.impactmalaria.com/EN/GP/Pour_tout_connaitre_sur_le_paludisme/Les_symptomes/ . Accessed November 5, 2006. [Context Link]

33. Newman RD, Parise ME, Barber AM, et al.: Malaria-related deaths among U.S. travelers, 1963–2001. Ann Intern Med. 2004;141(7):647–656. [Context Link]

34. Fernandez MC, Bobb BS. Malaria. Available at: http://www.emedicine.com/emerg/topic305.htm . Accessed January 4, 2006. [Context Link]

35. Korenromp EL, Williams BG, Gouws E, et al. Measurement of trends in childhood malaria mortality in Africa. Lancet Infec Dis. 2003;3(6):349–358. [Context Link]

36. Gubler DJ. Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century. Trends Microbiol. 2002;10(2):100–103. [Context Link]

37. Howard CR. Viral haemorrhagic fevers, perspectives in medical virology. Elsevier: Amsterdam 2005; Vol 11. [Context Link]

38. Centers for Disease Control and Prevention. Dengue Branch (Feb 2 & June 5, 2005) Available at http://www.cdc.gov/ncidod/EID/vol9no4/02-0267 . Accessed January 4, 2007. [Context Link]

39. Kotton C. Dengue fever. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4850a3 . Accessed January 4, 2007. [Context Link]