Mosquito-Borne Infectious Diseases: An Update for Clinicians

West Nile Virus (WNV)

WNV exploded into the national consciousness in 1999 when the first cluster of cases was documented in New York. The US tracking and reporting system was first established in 2003, but incomplete tracking from 1999 to 2004 demonstrates an estimated prevalence of 17,000 cases, including 6690 cases of neuroinvasive disease and 670 deaths. From that first outbreak in New York, WNV has now spread to all 48 contiguous states, with human disease reported in 42 states and avian, animal, and/or mosquito infection reported in the remaining 6 states.[4] Persons of all ages are equally susceptible to WNV, but the incidence of neuroinvasive disease and death is highest in persons aged 60-89 years.[5] The first case of intrauterine WNV transmission was documented in 2002. In 2003, the Centers for Disease Control and Prevention (CDC) received reports of 74 women infected with WNV during pregnancy; at the time of this report, most of these women who have been followed have delivered apparently healthy infants.[5] Additionally, a single case of WNV transmission through breast milk has been reported, though the infant remained healthy.[5]

WNV infections are most prevalent in the spring to late fall. Among seroconverted individuals, approximately 20% will develop symptoms with less than 1% developing neuroinvasive encephalitis and meningitis; the case fatality rate of severe disease is 10% but is higher in older age groups.[6] West Nile encephalitis is on the rise across the United States.

Although most infections are asymptomatic, WNV typically presents as a mild illness with a sudden onset, lasting 3-6 days. Symptoms include malaise, anorexia, nausea, headache, fever, rash, and lymphadenopathy. Indicators of neuroinvasive disease include headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness, and paralysis.

Diagnosis of WNV is verified by the presence of immunoglobulin M antibody (IgM Ab) in serum using the IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA); approximately 75% of cases will be positive within 1-4 days; virtually 100% are positive by 7-8 days. It should be noted that MAC-ELISA results will be positive if the patient has had a recent related illness, such as dengue fever, or vaccine, such as YFV17D (yellow fever vaccine). MAC-ELISA can remain positive for as long as 500 days. Presence of IgM in cerebrospinal fluid is diagnostic of neuroinvasive infection. Additionally, a complete blood count may demonstrate mild lymphocytopenia and anemia.

Treatment is supportive and there currently is no available vaccine. No data exists on the use of agents such as interferon or steroids for relief of symptoms.

Malaria

Malaria is caused by a parasite transmitted by the Anopheles mosquito; symptoms can develop anywhere from 6 to 8 days to several months after infection. It is the only mosquito-borne disease that can be prevented, treated, and cured by medication therapy because this treatment kills the parasite.

Symptoms occur in paroxysms/cycles of chills, fever, and sweating. The sequence of chills, fever, and sweats lasts approximately 10 hours, beginning with shivers, headache, nausea and vomiting, malaise, and anorexia, followed within a few hours by a temperature rise with hot, dry skin, and a rapid, bounding pulse, with possible delirium. When the temperature falls, profuse sweating occurs. The cycle of symptoms coincides with the bursting of the erythrocytes and reoccurs every 2 to 3 days.

Where malaria is found depends primarily on climatic factors such as temperature, humidity, and rainfalls; it is more likely to occur in tropical and subtropical environments. Although not indigenous to the United States, the CDC received reports of 1337 cases of malaria with an onset of symptoms in 2002 among persons in the United States or one of its territories. Compared with 2001, the number of reported malaria cases acquired in Asia and Africa increased slightly, whereas the number of cases acquired in the Americas decreased by 41.2%.

Of 849 US civilians who acquired malaria abroad, over a third reported that they had followed a chemoprophylactic drug regimen recommended by the CDC. Five patients became infected in the United States, 1 through congenital transmission, 1 probably via transfusion, and 3 whose infection source was unclear. Eight deaths were attributed to malaria.[7] A study in Canada noted that the diagnosis of malaria was initially missed in over 50% of cases, illustrating the importance of screening severely ill patients for recent travel to endemic areas.[8]

Dr. Hunter noted that malaria is a leading cause of death in children worldwide, responsible for 800,000 deaths annually in Africa. Additionally, children are more prone to develop serious sequalae such as cerebral malaria with delirium, disorientation, coma, and convulsions appearing between 10 and 16 days from the time of the mosquito bite. There are 4 types of malaria, Plasmodium falciparum being the most serious and responsible for the majority of deaths. Plasmodium vivax and Plasmodium ovale can sequester or lie dormant in the liver and therefore reappear or relapse by reentering the red blood cells (RBCs) after 45 days and up to 5 years later. Plasmodium malariae may relapse after many years, possibly because it lies dormant in the RBCs of the spleen.

Malaria can be fatal, though it is treatable with antimalarial drugs. The drug of choice for all 4 types of malaria is chloroquine; however, resistance is growing in both P falciparum and P vivax strains and is most notable in individuals from Afghanistan, East and Southeast Asia, East and West Sub-Saharan Africa, India, Iran, and South America. Primary treatment for chloroquine-resistant strains is sulfadoxine/pyrimethamine (Fansidar, Roche), amodiaquine, artemisinin, or atovaquone/proguanil (Malarone, GlaxoSmithKline).

P falciparum is increasingly resistant to sulfadoxine/pyrimethamine in Southeast Asia and South America.[9]

Dengue Fever

Perhaps the most chilling piece of Dr. Hunter's presentation was discussion of dengue fever, often referred to as "breakbone fever," a reference to the characteristic fever and severe muscle and joint pain characteristic of this infection. Transmitted by the Aedes aegypti mosquito worldwide and the Aedes albopictus mosquito in the United States, dengue fever is caused by 1 of 4 closely related, but antigenically distinct, virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4), of the genus Flavivirus, which produces a range of illnesses, from viral flu to hemorrhagic fever. It is especially dangerous for children. Infection with one of these serotypes provides immunity to only that serotype for life, so persons living in a dengue-endemic area can have more than 1 dengue infection during their lifetime.[10]

Dengue fever and dengue hemorrhagic fever are primarily diseases of tropical and subtropical areas, and the World Health Organization (WHO) reports 50 million to 100 million cases of dengue infection each year. The CDC annually documents 100 to 200 cases in the United States, mostly in people who have recently traveled abroad (although cases not associated with foreign travel have been reported in Texas and the Southeast United States); an outbreak occurred in Hawaii in 2001. Many more cases likely go unreported because some primary care providers do not recognize the disease nor query patients with flulike symptoms about recent travel. A report on travel-associated dengue fever detected in the United States between 2001 and 2004 noted that almost a third of patients reported recent travel to a Caribbean island during the 2 weeks before illness onset, 20% reported travel to Pacific islands, and just over 15% each to Asia, Central America, and South America.[11]

Dengue is found most notably in areas of uncontrolled urbanization and population growth, resulting in substandard housing, inadequate water, sewer and waste management systems, and poor or nonexistent public health infrastructure. Known prevention strategies, such as mosquito control systems, are often lacking in endemic countries.

As is the case for the other mosquito-borne infections, there is no specific treatment for dengue fever and most patients, with appropriate supportive care, will recover within 2 weeks. Parents should be educated on signs indicative of a hemorrhagic process in their children.

References

1. Hunter A. Mosquito borne disease. Program and abstracts of the American College of Nurse Practitioner's 2005 National Clinical Conference; October 13-16, 2005; Palm Springs, California.

2. Fradin MS, Day JF. Comparative efficacy of insect repellents against mosquito bites. N Engl J Med. 2002;347:13-18.

3. American Academy of Pediatrics Committee on Environmental Health. Follow safety precautions when using DEET on children. Available at: http://aapnews.aappublications.org/cgi/content/full/e200399v1. Accessed January 30, 2006.

4. Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases. West Nile Virus: Statistics, Surveillance, and Control. Available at: http://www.cdc.gov/ncidod/dvbid/westnile/surv&control05Maps.htm. Accessed January 30, 2006.

5. Hayes EB, Komar N, Nasci RS, Montgomery SP, O'Leary DR, Campbell GL. Epidemiology and transmission dynamics of West Nile virus disease. Emerg Infect Dis. 2005;11:1167-1173.

6. Watson JT, Gerber SI. West Nile virus: a brief review. Pediatr Infect Dis J. 2004;23:357-358.

7. Shah S, Filler S, Causer LM, et al. Malaria surveillance -- United States, 2002. MMWR Morb Mortal Wkly Rep. 2004;53:21-34.

8. Kain KC, Harrington MA, Tennyson S, Keystone JS. Imported malaria: prospective analysis of problems in diagnosis and management. Clin Infect Dis. 1998;27:142-149.

9. World Health Organization Expert Committee on Malaria. Twentieth Report, October 19-27, 1998. Available at: http://mosquito.who.int/docs/ecr20_1.htm. Accessed January 30, 2006.

10. Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases. Dengue Fever. Available at: http://www.cdc.gov/ncidod/dvbid/dengue/. Accessed January 30, 2006.

11. Centers for Disease Control and Prevention. Travel-associated dengue infections --- United States, 2001-2004. MMWR Morb Mortal Wkly Rep. 2005;54:556-558.