DENGUE FEVER DENGUE HEMORRHAGIC FEVER DENGUE SHOCK SYNDROME Infectious Agent of DF ¨Four immunologically related, ¨ single positive-stranded RNA viruses ¨ known as dengue viruses (four serotypes) ¨ nDENV – 1 nDENV – 2 nDENV – 3 nDENV – 4 n ¨Of the genus Flavivirus, family Flaviviridae ¨Are responsible for causing DF and DHF Global Dengue – historical rality ¨ ¤The four dengue viruses originated in monkeys ¤ ¤Independently jumped to humans from monkeys in Africa or Southeast Asia ¤ between 100 and 800 years ago Immunity ¨ ¨Infection with one DENV produces immunity ¨ against reinfection with that one viruses ¨ (short-term £ 9 months) ¨ ¨Infection with one serotype ¨ does not protect agains the others, ¨ and sequential infections (others serotypes) ¨ put people at great risk for DHF/DSS Epidemiology ¨ ¨Transmission occurs from the bite of an infected mosquito ¨ nAedes aegypti nAedes albopictus (rarely) n ¤Which are found throughout the world ¤Insects that transmit disease are vectors ¨ ¨ ¨ ¨ ¨Vector (Aedes) and virus ¨ is present throughout ¨ the tropical and subtropical zones nBetween n35 degrees North latitude n40 degrees South latitude ¨ C:\Users\Svatava\Pictures\PRACOVNÍ\HIV\VHH\AEDES AEGYPTI\9257_lores-Aedes aegypti.jpg dengue 3.jpg Geografic distribution of Dengue Epidemiology ¨Today about 2,5 billion people, ¨ or about 40% of the world´s population, ¨ live in areas where is a risk of dengue ¨ transmission ¨Dengue is endemic in at least 100 countries ¨ in Asia, the Pacific, the Americas, Africa ¨ and the Caribbean ¨South-east Asia and Western Pacific ¨ are the most serious affected by DF Dengue USA 2019 www.cdc.gov/dengue/statistics Epidemiology ¨ ¨The main risk of exposure for the traveler ¨ ¤Is in populated urban and residential areas ¤ ¤Dengue infections are often found ¤ in the urban areas of tropical nations, ¤ including Thailand, Singapore, Taiwan, ¤ Indonesia, Philippines, India and Brasil Epidemiology ¨ ¨The World Health Organization (WHO) estimates that ¨ ¤50 to 100 million infections occur yearly ¤Including 500 000 DHF cases ¤22 000 deaths, mostly among children ¤ ¨Not only is the number of cases increasing ¨ as the disease is spreading to new areas, ¨ but explosive outbreaks are occuring Global Dengue ¨Before World War II: ¤Sporadic outbreaks were reported n throughout the tropics and subtropics ¨After World War II: ¤The start of the 1st pandemic n due to transport of Aedes n around the world in cargo ¨Past 30 years: ¤Next pandemic of DF increased and developed n (urbanization, population growth…) dengue2008trend.jpg Risk for Dengue ¨The bite of one infected mosquito ¨can result in infection. ¨The risk of being bitten is highest during ¨ nThe early morning n (several hours after daybreak) nIn the late afternoon n (several hours before sunset) n ¨Because the female mosquito typically feets (bites) during these hours. The most risk for DF ¨ ¨During the rainy season ¨ (when Aedes mosquito populations are high) ¨ ¨However, mosquitoes may feed ¨ at any time during the day. nGlobally risk nespecially for travelers nAll year nAll day doba dešťů.jpg …not only during the rainy season Dengue ¨ ¨Is the second most common cause ¨ of hospitalization among travelers ¨ returning from the tropics ¨ (malaria is the most common) ¨ ¨More than 17 000 of travelers ¨ are hospitalised with dengue every year Geografic distribution of Dengue dengue 5.jpg Mosquito Aedes aegypti – breeding habitats ¨Is adapted to breed around human dwellings, where insects oviposit in uncovered water storage containers as well as miscellaneous containers holding water: nThe outdoor sculptures n (due to ability to retain water) nA small outdoor container, vases, flower dishes, cans nThe interior of a drainage pipe nAutomobile tires nStanding water containers... n Breeding habitats – stagnant water ¨ 17 C:\Users\Svatava\SVATAVA SNOPKOVÁ\AKTUÁLNÍ TVORBA - FINAL\DENGUE\6957_lores-vlhká půda.jpg C:\Users\Svatava\SVATAVA SNOPKOVÁ\AKTUÁLNÍ TVORBA - FINAL\DENGUE\6961_lores- potrubí.jpg The international trade in used tires is responsible for the significant worldwide expansion of dengue fever ¨ 18 C:\Users\Svatava\SVATAVA SNOPKOVÁ\AKTUÁLNÍ TVORBA - FINAL\DENGUE\6958_lores-pneumatuka.jpg C:\Users\Svatava\SVATAVA SNOPKOVÁ\AKTUÁLNÍ TVORBA - FINAL\DENGUE\PHIL_2608_lores - eradikace.jpg Numerous eggs of the DF mosquito vector, Aedes aegypti in any container in or around houses, which can hold water (jars, tins…) ¨ 5129_lores-vajíčka 19 Transmission of the Dengue Virus ¨ ¨Mosquitoes first become infected with DENV ¨ by feeding on the blood of a dengue-infected person ¨After the virus replicates for 8 – 12 days in the mosquito nThe mosquito can transmit DENV to many other people n ¨During epidemic of dengue, infection rates among those ¨ who have not been previously exposed ¨ to the virus are often 40% to 50% of population ¨But can reach 80% to 90% ¨ 21 C:\Program Files\Microsoft Office\MEDIA\CAGCAT10\j0302953.jpg C:\Program Files\Microsoft Office\MEDIA\CAGCAT10\j0302953.jpg C:\Program Files\Microsoft Office\MEDIA\CAGCAT10\j0302953.jpg C:\Program Files\Microsoft Office\MEDIA\CAGCAT10\j0302953.jpg C:\Program Files\Microsoft Office\MEDIA\CAGCAT10\j0302953.jpg C:\Program Files\Microsoft Office\MEDIA\CAGCAT10\j0302953.jpg C:\Program Files\Microsoft Office\MEDIA\CAGCAT10\j0302953.jpg C:\Users\Svatava\Pictures\PRACOVNÍ\HIV\VHH\AEDES AEGYPTI\9257_lores-Aedes aegypti.jpg 1. Dengue-infected person (viremia) 3. The virus replication for 8-12 days in the mosquito 2. Feeding on the blood by Aedes 4. Transmission of DENV to many other people by mosquito Mode of transmission ¨ ¨In the vast majority of infections nA mosquito bite is responsible ¨In rare cases dengue can be transmitted nBlood transfusion from infected donors nIn solid organ or bone marrow transplants nNeedlestick injuries nMucous membrane contact with dengue-infected blood nFrom an infected pregnant mother to her fetus n ¨Direct person – to – person transmission ¨ has not been documented ¤ Incubation ¨ ¨Usually begin 4 – 7 days after the mosquito bite ¨Typically last 3 – 10 days ¨ ¨Some people ¨ never have significant symptoms ¨ but can still infect mosquitoes ¨ ¨About half of people infected with DENV ¨ who live in areas where the virus is widespread are asymptomatic Clinical Manifestations ¨ ¨Dengue is a febrile illness ¨ due to mosquito-borne viruses ¨ ¨ flu – like illness ¨ ¨The clinical manifestations of symptomatic ¨ illness range ¨ from mild, undifferentiated febrile illness ¨ to classic DF or DHF. Clinical Manifestations of DF ¨ ¨DF is defined clinically by an acute febrile illness ¨ with two or more of the following symptoms: ¨ nHeadache, retro-orbital pains nGeneralized pains in the muscles n and bone („breakbone fever“) nLack of appetite, Chills, leucopenia… ¨Fever nOccuring for a period of 5 to 6 days n Clinical Manifestations ¨ ¨Skin rash qussually appears as the fever subsides q and last 2 – 4 days qmay be fleeting and maculopapular, generalized, often confluent qseen in about 10% of cases rush denguee.jpg flush - Kopie.jpg Clinical Manifestations ¨ ¨Other signs and symptoms include: ¤Flushed facies ¤ (usually ¤during the first 24 – 48 hours) ¤Nausea ¤Vomiting ¤Gastrointestinal disturbances… Flushed facies DF.jpg Diagnosis, laboratory nMild cases are very hard to diagnose nClinical symptoms of DF is very resemble of influenza symptoms - Flu – like illness ¨ ¨Fever is accompanied by: nLeucopenia, relative lymphocytosis nModerate trombocytopenia nAST > ALT (liver enzyme) nSerology (ELISA) for IgG and IgM antibodies ¨In case of febrile illness exlude: nMalaria, yellow fever, leptospirosis… nChikungunya, rickettsial illness… ¨ Treatment ¨ ¨There is no specific treatment for DF ¨MAINSTAY = Symptomatic and supportive care ¨ ¨HYDRATATION !!! – essential nIs the most important nOral and intravenous replacement n of fluid and electrolytes nSufficient circulating fluid volume n is the central feature of DF care ¨ moskytiéra 2.jpg Prevention (how can we protect) - control of mosquito vector in urban and rural locales - mosquito net - garment cover (for travelers), long-sleeved garment - repellents and insecticidal sprays moskyt. v čepici.jpg moskyr.jpg mosk. díte.jpg DENGUE HEMORRHAGIC FEVER (DHF) Dengue hemorrhagic fever (DHF) ¨A potentially lethal complication of dengue fever ¨ with hemorrhage and occasional shock ¨Was first recognized the 1950s during dengue epidemic ¨ in the Philippines and Thailand ¨ ¨Affects most Asian countries ¨Has become a leading cause of hospitalization and death among children in the region ¨Has not been seen in Africa ¨ Dengue hemorrhagic fever (DHF) ¨An estimated 500 000 people with DHF require hospitalization each year ¨A very large proportion of whom are children ¨Without proper treatment, fatality rates can exceed 20% ¨Adequate treatment can reduce death rates to less than 1% 52 Clinical Manifestations of DHF ¨ ¨Approximately 1% of patients with DF develop DHF as the fever subsides ¨Usually 3 – 7 days following the onset ¨The hallmark of DHF is evidence of vascular leakage ¨ ¨Severe cases are diagnosed based on the following: nHigh fever for 2 to 7 days nHemorrhage nGastrointestinal bleeding, Ecchymoses, Effusions… nHepatomegaly ¨ DHF is defined: ¨ ¨By the presence of all the following symptoms: 1.Fever nor recent history of fever lasting 2 – 7 days 2.Any hemorrhagic manifestation 3.Trombocytopenia nPlatelet count < 100 000 mm3 4.Evidence of increase vascular permeability nHemoconcentration nPleural or abdominal effusion nHypoalbuminemia, hypoproteinemia Dengue HF C:\Users\Svatava\Pictures\PRACOVNÍ\dengue\DENGUE\HH dengue.jpg 37 C:\Users\Svatava\Pictures\PRACOVNÍ\dengue\DENGUE\HH dengue - Kopie.jpg dengue e.jpg Dengue HF DHH.jpg dengue 44.jpg pulmonary hemorrhage dengue.jpg Laboratory n nLeucopenia, relative lymphocytosis nTrombocytopenia nAnemia nElevated hematocrit, hemoconcentration nDehydratation nAST > ALT (liver enzyme) nSerology (ELISA) n for IgG and IgM antibodies (to dengue virus) Treatment ¨ ¨There is no specific treatment for DF/DHF ¨Symptomatic and supportive care ¨Aspirin is avoided ¨ (it may exacerbate the bleeding tendency due to the hemorrhagic nature ¨ of the severe illness) ¨HYDRATATION !!! – essential nOral and intravenous replacement n of fluid and electrolytes nCirculating fluid volume n is the central feature of DF care ¨ DENGUE SHOCK SYNDROME (DSS) Dengue Shock Sy is defined: ¨ ¨As a syndrom in any case patient ¨ who meets the ¨ nCriteria for DHF n and has nHypotension nNarrow puls pressure (£ 20 mmHg) nOr frank shock nCirculatory failure nDeath within 12 to 24 hours Patophysiology of DHF/DSS ¨ ¨Infection with one DENV produces immunity ¨ against reinfection with that one viruses ¨ (short-term £ months) ¨ ¨Infection with one serotype ¨ does not protect agains the others, ¨ and sequential infections (others serotypes) ¨ put people at great risk for DHF/DSS ¨ DHF/DSS ¨ ¨Is an immunopathologic syndrome ¨Antibody from a first infection fals ¨ and second dengue virus type infection is present ¨Even very small numbers of antibody to one serotype of dengue form immune complex with other serotype of dengue ¨Followed an acute vascular permeability syndrome ¨ 9 months Ig-from a first inf.fals second inf. is present Immune complex (Ig-Ag) is formed Þvascular permeability sy DHF/DSS ¨Occurs in: ¤Infants infected for the first time ¤ who have acquired ¤ maternal dengue antibody in utero ¤Children and, less commonly, ¤ adults during ¤ a second dengue virus infection ¨Is more severe in: ¤Whites and Asians ¤ (versus black people) ¤Females (versus males) ¤Well-nourished children ¤ (versus malnourished) ¨ dítě dengue.jpg dengue likvidace.jpg Dengue prevention currently relies on public health and community-based Aedes aegypti control programs to remove and destroy mosquito-breeding sites ¨ ¨ ¨ ¨ ¨ ¨Thank you for your attention…