Infectious Diseases in Clinical Practice:
Chikungunya Continues to Expand: What Lies Ahead?
Wilson, Mary Elizabeth MD, FACP, FIDSA
From the Harvard Medical School, Harvard School of Public Health, Mount Auburn Hospital, Cambridge, MA.
Reprints: Mary Elizabeth Wilson, MD, FACP, FIDSA, 1812 Kalorama Square NW, Washington, DC 20008-4022. E-mail: email@example.com.
Chikungunya virus has moved out of Africa into populous areas of Asia. It caused one outbreak in Italy in the summer of 2007,1,2 and it threatens other areas with competent mosquito vectors and temperatures that are warm enough to allow the virus to become transmissible from mosquitoes. In the endemic areas in Africa, local primates and perhaps other animals are involved in the transmission cycle, but the virus can cause explosive outbreaks with high attack rates in a human-mosquito-human cycle in urban and periurban areas.3 The level of viremia in infected humans is high, exceeding 109, providing a ready source of virus4 for mosquitoes.
Sandro Cinti in this volume provides an excellent review of the history of this virus and describes recent events. The main mosquito vectors, Aedes aegypti and Aedes albopictus, are now widely distributed in the world, thanks to global trade.5,6 Ships have carried mosquito eggs and larvae in used tires and with other goods to many countries where A. albopictus has now become established. Tatem et al7 analyzed shipping routes, volume of traffic, climate data, and the distribution of A. albopictus outside of its original home in Asia. They found that when climate was suitable for the survival of the mosquito, shipping volume predicted the likelihood of mosquito invasion in a new port or country. A. albopictus, the Asian tiger mosquito, was introduced into the US in the 1980s probably via used tires from Asia and has since spread to at least 26 states. A recent study of A. albopictus and A. aegypti from Florida has documented that these mosquito strains can be infected in the laboratory with chikungunya virus, which can disseminate to salivary glands, indicating that mosquitoes that inhabit the US are competent to transmit the virus.8
Although the virus can be vertically transmitted from mother to infant and has been transmitted in the health care setting (exposure to infective blood) and presumably can be transmitted by transfusion or transplantation of infective blood or other tissues, the main culprit in transmission is the mosquito.9
Presence of a competent mosquito does not necessarily mean that infection will transmitted or will become established in an area, even if a viremic person is present. Presence of screens and air conditioning will reduce the likelihood that local mosquitoes will become infected and transmit virus. Temperatures must be warm enough to allow the virus to multiply, disseminate, and reach salivary glands of the mosquito so that it can transmit virus before it dies. The speed of this process in the mosquito is highly dependent on temperature. The warmer the temperature the faster the process-at least up to a point. To introduce the virus into a new region, the viremic traveler must arrive during hot weather, as happened when chikungunya virus in a person from India sparked an outbreak in northern Italy starting in July.10
What factors have been associated with the dramatic recent events?11 Several can be noted. Expanded travel and trade have contributed to the movement of mosquito vectors and human hosts, including infected humans, around the globe.12 Many of the islands in the Indian Ocean where massive outbreaks occurred are popular tourist destinations, especially for European travelers. Lack of surveillance for mosquito vectors and poor control programs have allowed mosquito vectors to proliferate. Most of the global population growth today is occurring in urban areas in low latitude countries, so the susceptible population is growing. In addition, recent studies document a mutation in the envelope protein gene of the virus that is associated with enhanced replication of the virus in A. albopictus and more rapid dissemination into the mosquito salivary glands.13 The virus with this mutation was absent initially in the outbreak on Reunion island but was later found in 90% of isolates, suggesting that the mutation confers increased fitness. The outbreak on Reunion was massive, causing an estimated 266,000 cases, 34% of the total population of the island.
What lies ahead? Historically when chikungunya virus caused outbreaks outside of Africa, especiallyin Asia, it would then disappear from those areas, often for decades. What is different today is that the global human population is larger and more interconnected than ever, competent mosquito vectors inhabit many large urban areas in tropical and subtropical regions, and recent mutations in the virus seem to enhance its capacity to spread rapidly. In areas already affected by massive epidemics with high attack rates, populations will have substantial protection for some time because of immunity induced by infection. Large susceptible populations remain, however, including large urban areas in tropical areas of the Americas. Those that have had recent outbreaks of dengue, which indicates human exposure to Aedes mosquitoes, would be at highest risk. Clinicians globally need to be familiar with the clinical manifestations of chikungunya fever as travelers will continue to carry infections home, as long as outbreaks continue in Asia and elsewhere.
1. Charrel RN, de Lamballerie X, Raoult D. Chikungunya outbreaks-the globalization of vectorborne diseases. N Engl J Med. 2007;356:769-771.
2. Rezza G, Nicolleti L, Angelleti R, et al. Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet. 2007;370:1840-1846.
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5. Reiter P, Fontenille D, Paupy C. Aedes albopictus as an epidemic vector of chikungunya virus: another emerging problem? Lancet Infect Dis. 2006;6:463-464.
6. Enserink M. A mosquito goes global. Science. 2008;320(5878):864-866.
7. Tatem AJ, Hay SI, Rogers DJ. Global traffic and disease vector dispersal. Proc Natl Acad Sci USA. 2006;103:6242-6247.
8. Reiskind MH, Pesko K, Westbrook CJ, et al. Susceptibility of Florida mosquitoes in infection with chikungunya virus. Am J Trop Med Hyg. 2008;78(3):422-425.
9. Brouard C, Bernillon P, Quatresous I, et al. Estimated risk of chikungunya viremic blood donation during an epidemic on Reunion Island in the Indian Ocean, 2005 to 2006. Transfusion. 2008.
10. Charrel RN, de Lamballiere X, Raoult D. Seasonality of mosquitoes and chikungunya in Italy. Lancet Infect Dis. 2008;8:5-6.
11. Simon F, Savini H, Parola P. Chikungunya: a paradigm of emergence and globalization of vector-borne diseases. Med Clin N Am. 2008;92:1323-1343.
12. Chen LH, Wilson ME. The role of the traveler in emerging infections and magnitude of travel. Med Clin N Am. 2008;92:1409-1432.
13. Tsetsarkin KA, Vanlandingham DL, McGee CE, et al. A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathogens. 2007;3(12):1895-1906.
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