The Role of Mosquito in Emerging I nfectious D iseases

1. The Role of Mosquito in Emerging Infectious Diseases Brandi Mueller M.S. PhD Candidate in Tropical Medicine University of Hawaii July 1, 2010

2. Outline • Mosquito-borne diseases • The mosquitoes who spread them • Ecology • Epidemiology • Control • Climate change

3. Dengue Virus • Most important Mosquito-borne virus in the world • Spread by Aedes aegyptiand also other less-competent Aedes species (including Aedes albopictus) • WHO estimates more than 2.5 Billion people are at risk • Genus: Flavivirus • Family: Flaviviridae • Made up of more than 50 viruses including Yellow Fever, West Nile, Japanese encephalitis, and Hepatitis C • Emergence attributed to • Population Growth • Increased urbanization • Mosquito expansion • Globalization (Gubler, 1998) • No vaccine, no antiviral, difficult and expensive to diagnose • No animal model – making it difficult to study

4. Wide spectrum of disease • Mild dengue fever: mild to severe acute febrile illness/flu-like symptoms to fever, joint-pains, headaches, nausea, vomiting, and rash • Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) • Severe form of disease • Occurs mostly in young children and sometimes adults • Nonspecific early stages, characterized by capillary leakage and hemorrhagic manifestations on skin, bleeding gums, GI hemorrhage • Can lead to blood loss or shock caused by plasma leakage • No treatment except symptomatic care and can be fatal without proper care • 4 antigenically distinct serotypes: • Each thought to be introduced from non-human primates (Wang et al., 2000 and Twiddy and Holmes, 2003). • Hyperendemicity – Geographically expanded in last 30 years • More than 1 serotype co-circulating • Includes Puerto Rico, Caribbean, Central/South America, South East Asia and more

5. Increased Virulence • Antibody-dependent Enhancement Hypothesis • Infection with a second serotype will cause more severe disease • Existing heterologous dengue antibody forms and antigen-antibody complex that is bound and internalized by macrophages • Virus is not neutralized in the macrophages and it is able to replicate • ADE leads to increased viremia, leading to increased risk of transmission • Strain Evolution/Variation • RNA viruses have high strain mutation rates • Adaptive evolutionary response may cause more severe strains to be selected for due to • Increase virus replication • Increase dissemination/decrease dissemination time • Survival • Immune Evasion • Transmission efficiency • Both???

6. Yellow Fever • Acute viral hemorrhagic disease • “Yellow” due to jaundice that affects many patients • Death can be as high as 50% in untreated patients • ~200,000 cases a year • Common in Latin America and Africa • Diagnosis • Easily confused with other diseases (malaria, typhoid, dengue hepatitis) • Serum tests and PCR • No cure or treatment • Symptomatic care • Vaccine • Safe, affordable, long-term immunity vaccine available • Sylvatic cycle • Monkeys

7. Chikungunya • First described in 1952 in Tanzania • Currently occurs in Africa, Asia, Indian subcontinent • 2007 outbreak in Italy • Alphavirus, Family Togavirdae • Symptoms can be similar to dengue • Muscle pain, headache, nausea, fatigue and rash • Makes diagnosis difficult • Serological tests and PCR are best methods available • No drugs or vaccine • Treat symptomatically

8. Malaria • 225+ million cases a year • Almost 1 million deaths from malaria a year • Mostly among African children • In Africa a child died ever 45 seconds (WHO) • Four types of malaria • Plasmodium falciparum • P. vivax • P. malariae • P. ovale • P. knowlesi??? • Symptoms • Acute febrile illness – fever, headache, chills, vomiting • P. falciparum can lead to death without treatment • Relapses with P. vivax and P. ovale

9. Malaria • High risk populations included • Young children • Non-immune pregnant women • HIV infected (especially HIV infected children and pregnant women) • International travelers • Diagnosis • Microscopy, rapid test • Treatment • Prophylaxis • Many different malaria drugs • All have shown development of resistance • Important to know what resistance levels are in place you are living/traveling

10. West Nile Virus • First described in Western Nile region, Uganda in 1937 • Re-emerged in New York, 1990 • Has many reservoirs • Birds, horses, pets (dogs, cats, rabbits), humans • Flaviviridae, same family as dengue • Symptoms • Fever, muscle pain, headache, nausea • No treatment or vaccines

11. Mosquito borne diseases and the mosquitoes that spread them Anopheles • Aedes • Dengue • Yellow Fever • Chikungunya • West Nile • Malaria www.stanford.edu • Culex

12. Mosquito Ecology • Only female mosquitoes spread disease • Where do mosquitoes live? • Aedes • Urban mosquitoes – like human habitats • Breed in uncovered water containers, trash (old tires, etc), any standing water • Day biters – dawn and dusk • Anopheles • Rural mosquitoes • Breed in river/lake run-off, swamps, • Night biters – most active 10pm-2am • Culex • Breed in pools, fishponds, standing water in fields, slow running streams and ditches • Night biters – right after dark • Zoophagous – but also feed on humans

13. Mosquito Control • Due to lack of effective treatments and vaccines the current most useful way to prevent mosquito-borne diseases is by controlling the vectors • Spraying • Mosquito nets • Larvacides - Reducing breeding sites

14. Control • Adult Control • Mosquito traps • Mosquito spray • Larval Control • Remove containers with water • Cover water-storage containers • Clear stagnant water • Larvicide • Copepods • Fish

15. How does ecology play a role in control? • Mosquito Habitat • Biting Time • Mosquito nets for Aedes? • Resistance?

16. Control • Every place requires it’s own control plan • What works in one place may not work in another • Community-based (bottom-up, not top-down)

17. Community Involvement • Remove any sort of water-containing sources • Change water in potted plants often • Remove trash including old tires • Cover water-storage containers • Install mosquito screens on windows and doors • Bed nets • Insect repellant • Light colored clothing

18. Surveillance • Mosquitoes population sizes can be estimated in different ways • Oviposition traps – traps are set up to monitor the breeding of mosquitoes • Adult surveys – light traps, CO2 traps, etc • Presence of vector only does not indicate transmission of disease will take place

19. Climate Change and Infectious Diseases

20. Climate Change • Any long-term change in the average climate due to anthropogenic or natural causes (IPCC, 2007) • Predicted • World-wide increase of average surface temperature • Changes in precipitation • Warming of polar regions • Sea level rise • Warming of nights • Migration of disease causing vectors • ~0.65˚C increase in last 50 years • Predictions at end of 21st century • Global mean surface temperature rise of 0.6-4.0ºC • Sea level increase of 0.18-0.59m

21. Arboviruses(and other Arthropod vector pathogens) • Infections that are transmitted to humans and other animals by blood-feeding arthropods (Gubler, 2001) • Pathogens that spend part of their life cycle in a cold-blooded arthropod vector • Mosquitoes, ticks, sand flies, fleas, etc. • Vectors and pathogens lack thermostatic mechanisms • Change in climate can cause change in vector population and amplify the disease in host • Malaria, Dengue, Yellow Fever – transmitted directly from mosquitoes to human • Plague, Lyme Disease – fleas, ticks • Leishmaniasis – sand flies www.ismarden.com

22. Pathogen Level • Temperature can influence: • Speed of replication • Pathogen development • Speed of incubation time (warmer = decreased incubation) • Survival

23. Vector Level - Mosquitoes • May have shorter gonotrophic cycles in increased temperatures • Warmer temperatures leads to smaller adults (need multiple blood-meals) • Shorter life span – increase or decrease transmission? • Aedes – the “urban” mosquito – Yellow Fever and Dengue Fever • Can transmit at least 22 arboviruses • Anopheles – Malaria • Culex – West Nile, Japanese encephalitis, St. Louis encephalitis

24. Vector Population Dynamics and Geographic Range • Will vector habitat range change? What is more likely to potentially change? • Change in rate of population growth • Disrupt ecosystem balance • Change in vector or pathogen habitat • Change in transmission season • Rainfall, temperature, and other weather variability play a role in vectors and their pathogens (Gubler, 1997) • Vectors and their pathogens often have seasonal or annual patterns

25. “An overall increase in person-months of exposure risk to malaria was 16%-28% by 2100” (Haines and Patz, 2004). Malaria Climate change and Malaria. (2005). In UNEP/GRID-Arendal Maps and Graphics Library. http://maps.grida.no/go/graphic/climate_change_and_malaria.

27. Malaria, dengue and yellow fever in the USA • Susceptible mosquitoes still live in these areas • Better living conditions, sanitation, agricultural practices and mosquito control have been attributed to reduction (Gubler, 2001) • Climate change may lead to severe conditions or socioeconomic changes to reduce these better living conditions • West Nile • Warm winters, followed by hot, dry summers favor transmission cycle among birds, urban mosquitoes and human (Epstein, 2001) • 1999 outbreak in New York

28. El Niño-Southern Oscillation • Ocean-atmosphere system that causes intense weather changes in the Tropical Pacific • Sea surface temperatures increase in west and cool in the east • Extreme rains and droughts • Increased rain can lead to more/new breeding sites • Droughts increase host-vector interactions by sharing few water sources • Climate change may lead to more ENSO Climate impacts of El Niño Phenomenon in Latin America and the Caribbean. (2005). In UNEP/GRID-Arendal Maps and Graphics Library. http://maps.grida.no/go/graphic/climate_impacts_of_el_ni_o_phenomenon_in_latin_america_and_the_caribbean.

29. El Niño Events • South Pacific island studies show that ENSO increased temperature and rainfall trigger an increase in Dengue on endemic islands (Hales, 1999) • Colombia and Peru have higher malaria cases during ENSO events (Poveda, 2001) • Venezuela and South Africa has low malaria transmission during ENSO (dry period) and higher transmission during La Niña (Barrera, 1999 and Mabaso, 2007)

30. Indirect and Other Factors • Difficult to separate climate influences from others: • Other environmental factors • Genetic adaptation • Resistance (drugs or insecticides) • Increased travel • Pathogen importation • Vector importation • Population immunity • Malaria • Yellow Fever • Human health • malnutrition • Interactions with multiple diseases

31. Interdisciplinary Problem

32. Conclusions • Ecology, development, behavior, and survival of arthropods is largely influenced by climate • Temperature affects pathogen replication speed and incubation time • Altered distribution of diseases • Importance of current research • Monitor regional climate • Monitor pathogen and vector ecology • Spatial and temporal scales • Consider all factors

33. References • Patz, JA. et al. 2005. Impacts of regional climate change on human health. Nature. 438(17):310 • Watson, TW. et al. 2005. Environmental health implications of global climate change. Journal of Environmental Monitoring. 7:834 • Watson, JT. et al. 2007. Epidemics after natural disasters. Emerging Infectious Disease. 13(1):1 • Kuhn, K. et al. 2005. Using climate to predict infectious disease epidemics. WHO • Gubler, DJ. et al. 2001. Climate variability and change in the United States: potential impacts on vector- and rodent-borne diseases. Environmental Health Perspectives. 109(2):223 • Poveda, G. et al. 2001. Coupling between annual and ENSO timescales in malaria-climate association in Colombia. Environmental Health Perspectives. 109(5):489 • Epstein, PR. 2001. West Nile virus and the climate. Journal of Urban Health. 78(2):367 • Nicholls, N. 1993. El Niño-Southern Oscillation and vector-borne disease. Lancet.342:1284. • Alley, R.B. 2004. Implications of abrupt climate change. Transactions of the American Clinical and Climatological Association. 115:305-317. • Faruque, S.M., et. al. 2000. Sunlight-induced propagation of the lysogenic phage encoding cholera toxin. Infections Immunity. 68:4795-4801. • Kovats, R.S. 2000. El Niño and human health. Bulletin of World Health Organization. 78(9):1127-1135. • Wlicox, B.A., Colwell, R.R. 2005. Emerging and reemerging infectious diseases: biocomplexity as an interdisciplinary paradigm. Ecohealth. 2(4):244-257 • Haines, A. and Patz, J.A. 2004. Health effects of climate change. JAMA. 291:99-103. • Reiskind, MH., et al. 2008. Susceptibility of Florida mosquitoes to infection with chikungunya virus. Am J Trop Med Hyg. 78(3):422