MODULE 3: Transmission Dengue Clinical Management Acknowledgements This curriculum was developed with technical assistance from the University of Malaya Medical Centre. Materials were contributed by the Ministry of Health, Singapore, the United States Centers for Disease Control and Prevention, and the University of Malaya Medical Centre.
Dengue virus (DENV) Single-stranded RNA virus Member of Flavivirus family Tick-borne encephalitis virus Selected Flaviruses West Nile virus Murray Valley encephalitis virus Japanese encephalitis virus St. Louis encephalitis virus DENV 1 DENV 3 DENV 2 DENV 4 Yellow Fever virus
Dengue virus (cont.) Four serotypes (really species): DENV-1, -2, -3, -4 All cause full spectrum of disease Infection confers lifelong serotype-specific immunity and short-term (2-3 months) cross-immunity Humans can have four infections in a lifetime Genetic variation within serotypes Some genetic variants thought to be more virulent Dengue virus causes an acute febrile illness (called dengue)
Transmission of dengue virus Dengue is passed from human-to-human by the bite of female mosquitoes: Aedes aegypti is most common; Aedes albopictus can also sustain transmission. Ae. aegypti is very efficient vector: Anthropophilic (prefers to feed on humans) Frequently bites several times Thrives in close proximity to humans Humans are main reservoir for the virus, though monkeys may be the sylvatic reservoir in S.E. Asia and W. Africa 1 Mosquito is distributed mostly between latitudes 35 N and S Mosquito remains infected for life ( 3 weeks) http://www.who.int/csr/disease/dengue/impact/en/ 1 Vasilakis et al. Nat Rev Microbiol, 2011; 9:532 541.
Transmission of dengue virus human-to-human transmission via the bite of an infected mosquito Febrile, viraemic boy with dengue virus infection Time
Transmission of dengue virus human-to-human transmission via the bite of an infected mosquito Mosquito bites boy and gets dengue virus in the blood meal Time
Transmission of dengue virus human-to-human transmission via the bite of an infected mosquito Affected by temperature Dengue-infected mosquito bites girl and 8 to 12 days later Extrinsic Incubation Period within the mosquito Time
Transmission of dengue virus human-to-human transmission via the bite of an infected mosquito transmits the dengue virus to her Time
Transmission of dengue virus human-to-human transmission via the bite of an infected mosquito 3 to 14 days later Intrinsic Incubation Period within the girl Girl can pass dengue virus to another mosquito if bitten while she is viraemic Time
Breeding areas and transmission Ae aegypti immature stages are typically found in water-filled habitats associated with human habitation; Lays eggs in artificial, water-holding containers, and occasionally bromeliads and tree holes Primarily feeds from dawn to dusk, rests in dark areas and bites indoors Most female Ae. aegypti mosquitoes spend their lifetime in or around the houses where they emerge as adults, meaning people rather than mosquitoes rapidly move the virus within and between communities Credit: WHO Breeding sites: plants, pools, water-filled buckets, used tires, empty oil drums, water storage containers etc.
Life-cycle of Aedes aegypti 2 days Female lays 100 to 120 eggs inside containers (above water) five times in her life time. WHO/EHI Singapore Approximately 6 days Eggs can survive for up to 6 months. Eggs hatch when submerged in water, a process that takes less than 24 hours. Note: Fecundability dependent on environmental conditions such as rain, humidity and temperature. The total time for development is dependent upon water temperature and food supply, and typically ranges from 4 to 10 days. Larvae die at temperatures below 10 C and above 44 C.
Other routes of transmission Evidence of transmission of dengue through receipt of donor organs or tissue 1 Bone marrow transplant and renal transplant Evidence of transmission of dengue through receipt of blood products (RBC transfusion) 2,3 Seven reports of transmission after occupational exposure in a health-care setting 4 Use standard precautions 1 Wilder-Smith A et. al. Threat of dengue to blood safety in dengue-endemic countries. EID, 2009; 15(1):8-11. 2 Chuang et al. Review of dengue fever cases in Hong Kong during 1998 to 2005. Hong Kong Med J, 2008; 14:170-177. 3 Tambyah et al. Dengue hemorrhagic fever transmitted by blood transfusion. N Engl J Med, 2008; 359:1526-1527. 4 Mohammed H et al. Dengue virus in blood donations, Puerto Rico, 2005. Transfusion, 2008; 48:1348-1354.
Vertical transmission DENV can be transmitted from the mother to the fetus in utero or to the neonate at parturition (vertical transmission); however, only 35 cases have been reported in literature.* Rates of vertical transmission vary and may depend on severity of maternal infection and timing of infection Reported cases were symptomatic and had a symptomatic mother with infection late in pregnancy or at delivery * Pouliot SH et al. Maternal dengue and pregnancy outcomes: a systematic review. Obstetr Gynecol Survey, 2010.
Vertical transmission (cont.) Average time between mom and newborn onset is 7 days (range: 5 13 days) ~ similar to intrinsic incubation Most congenital cases described had fever plus thrombocytopenia and hepatomegaly Half had hemorrhagic manifestation One quarter had pleural effusion and/or rash Clinical presentation not associated with maternal immune status or mode of delivery * Pouliot S.H., et. al. Maternal dengue and pregnancy outcomes: a systematic review. Obstetr Gynecol Survey 2010.
Primary prevention measures Avoid being bitten (just after dawn until just after sunset) Use repellent* containing: DEET: Off!, Cutter, Sawyer and Ultrathon Picaridin: Cutter Advanced, Skin So Soft Bug Guard Plus Picaridin Oil of lemon eucalyptus: Repel IR3535: Skin So Soft Bug Guard Plus IR3535 Expedition Wear long-sleeved shirt and long pants when outdoors Spray permethrin or DEET repellents on clothing Use screens in house Kill adult mosquitoes and larva in your home * For more information see http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/protection-againstmosquitoes-ticks-insects-arthropods.aspx