persons may be infected up to four times. virus.

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1 DENGUE FEVER פנימית א וולפסון מחלקה ד"ר שירלי שפירא בן דוד

2 The virus Flaviviridae (single-stranded, nonsegmented RNA viruses) Has four serologically distinct serotypes (DEN-1, DEN-2, DEN-3,and DEN-4). Infection with one serotype confers long-term immunity only to that serotype, and therefore persons may be infected up to four times. Humans are the main reservoir for the dengue virus.

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4 The vector Dengue virus is transmitted by mosquitoes of the genus Aedes found worldwide in the tropics and subtropics, is the principal vector. It is highly susceptible to dengue virus, feeds preferentially on human blood, a daytime feeder, has an almost imperceptible bite, and is capable of biting several people in a short period for one blood meal. The mosquito is well adapted to life in urban settings and typically breeds in clean, stagnant water in containers that collect rainwater.

5 Epidemiology Dengue virus is now the most common cause of arboviral disease in the world, with an estimated annual occurrence of 100 million cases of dengue fever and 250,000 cases of dengue hemorrhagic fever and a mortality rate of 25,000 per year. Dengue virus infection has been reported in more than 100 countries. Most cases of dengue hemorrhagic fever are reported from Asia, where it is a leading cause of hospitalization and death among children.

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7 In travelers Dengue fever has been diagnosed d in an increasing proportion of febrile travelers returning from the tropics, ranging from 2 percent in the early 1990s to 16 percent more recently. The second most frequent cause of hospitalization (after malaria) among travelers returning from the tropics. Therateofself-reported reported dengue fever among Israeli travelers to Thailand in 1998 was 3.4 per 1000 travelers.

8 Risk factors Risk factors among travelers acquiring dengue relate to the duration, season, and destination of travel. Most dengue virus infections in travelers are acquired in Asia, followed by the Americas, with only a small proportion in Africa.

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10 Transmission Nonvecror transmition- Isolated reports of returning travelers who have transmitted dengue virus infection to health care workers in countries where dengue is nonendemic by way of needlestick injury or mucocutaneous exposure to blood, seen only rarely. Vertical transmission of dengue rare - comparing outcomes of infants born to women infected with dengue vs. uninfected, no difference in rates of preterm birth, mode of delivery, postpartum hemorrhage, low birth weight, neonatal outcomes

11 Pathogenesis Infected mosquito virus replicates in regional lymph nodes and is disseminated through the lymphatic system and blood to other tissues Replication in the reticuloendothelial system and skin Viremia. The incubation period ranges from 3 to 14 days, but it is usually 4 to 7 days. Infection with dengue virus of any of the four serotypes causes a spectrum of illness, ranging from no symptoms or mild fever to severe and fatal hemorrhage, depending largely on the patient s age and immunologic condition.

12 Development of severe hemorrhagic disease Although h the mechanisms are not fully understood. d The main risk factor- secondary infection with another serotype. This antibody-dependent enhancement amplified cascade of cytokines and complement activation endothelial dysfunction, platelet destruction, and consumption of coagulation factors plasma leakage and hemorrhagic manifestations. The severity of the disease also depends on the strain and serotype of the infecting virus, the age and genetic background of the patient, and the degree of viremia.

13 Diagnosis

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15 Primary infections are characterized by an increase in dengue-specific IgM antibodies 4 to 5 days after the onset of fever and by an increase in IgG antibodies after 7 to 10 days. A laboratory-based diagnosis of dengue is often unavailable at the time of care, a clinical diagnosis is initially made on the basis of clinical manifestations and laboratory features developing over a period of time and as other potentially life-threatening ea e diseases, such as malaria, are ruled out. Commercial point-of-care tests for dengue antigen may be clinically useful for diagnosis of acute dengue virus infection but vary in sensitivity.

16 Dengue can be ruled out if: symptoms begin more than two weeks after the traveler or immigrant has left an area where the disease is endemic. Fever that persists more than 10 days usually rules out dengue.

17 DD Malaria, Typhoid fever, Leptospirosis, Chikungunya, West Nile virus infection, Measles, Rubella, acute Human Immunodeficiency Virus conversion disease, Epstein Barr virus infection, Viral hemorrhagic fevers, Rickettsial diseases, Any other disease that t can manifest in the acute phase as an undifferentiated febrile syndrome.

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19 Clinical aspects

20 Classic dengue fever Sudden onset of fever, severe headache, retro-orbital orbital pain, fatigue, often associated with severe myalgia and arthralgia. The fever usually lasts 5-7 days. A rash, occurs in up to 50% patients, scarlatiniform or maculopapular develops between day 2-6 and spreads centrifugally, lasts 2-3 days. Petechiae may occur as fever decreases. Diffuse erythema and late desquamation of hands and feet may occur (may be confused with toxic shock syndrome). Other signs and symptoms: flushed facies, lymphadenopathy, injected conjunctivae, an inflamed pharynx, mild respiratory and gastrointestinal symptoms. Very rare complications: myocarditis, hepatitis, and neurologic abnormalities, such as encephalopathy and neuropathies.

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22 Laboratory findings Thrombocytopenia, leukopenia with lymphopenia, p Mild-to-moderate elevations of hepatic aminotransferases and lactate dehydrogenase, Hyponatremia

23 Classic dengue fever in travelers, although selflimiting and rarely fatal, can be incapacitating, may halt travel, and may require hospitalization and even evacuation and a return home. In one series es from Israel, 30 percent of travelers who contracted dengue fever were evacuated, and 66 percent were hospitalized.

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26 Dengue hemorrhagic fever The hallmark of dengue hemorrhagic h fever is capillary leakage, accompanied by hemorrhagic manifestations. First days- similar. Plasma leakage develops four to seven days after the onset of the disease. Abdominal pain and vomiting, restlessness, a change in the level of consciousness, and a sudden change from fever to hypothermia may be the first clinical warning signs and are often associated with a marked decrease in the platelet count.

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28 Dengue hemorrhagic fever Diagnosis: i Triad of symptoms and signs: 1. Hemorrhagic manifestations; 2. A platelet l t count of less than 100, per cubic millimeter; 3. Objective evidence of plasma leakage, shown either by fluctuation of packed-cell volume or by clinical signs of plasma leakage, such as pleural effusion, ascites, or hypoproteinemia. i Mortality rates from dengue hemorrhagic fever can range as high as 10 to 20 percent, but they are as low as 0.2 percent in hospitals with staff experienced in the management of the disease.

29 Dengue shock Dengue shock syndrome is characterized by a rapid, weak pulse with a narrowing pulse pressure of less than 20 mm Hg, or profound hypotension. The duration of shock is short. Patients either e recover e rapidly after appropriate ate volume-replacement therapy or die within 12 to 24 hours The mortality rate is up to 40 percent.

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31 Management No specific treatment. t t Fluid replacement- reduce mortality rates due to dengue hemorrhagic fever and dengue shock syndrome. Treatment is based on symptoms and supportive Mild or classic dengue is treated with antipyretic agents such as acetaminophen, bed rest, and fluid replacement Most cases can be managed on an outpatient basis. Platelet counts and hematocrit determinations should be repeated at leas every 24 hours to allow prompt recognition of the development of dengue hemorrhagic fever and institution of fluid replacement

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34 Admisson Patients t with a platelet l t count of less than 100, admit to a hospital since they have the highest risk of the development of dengue hemorrhagic fever The critical period is often 4-7 days after onset of the illness. A decrease in the platelet count, which usually precedes the rise in hematocrit, is of diagnostic and prognostic value in cases of dengue hemorrhagic fever. A rise in the hematocrit of 20 percent indicates considerable plasma loss intensive care with intravenous replacement of fluids

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38 Prevention No vaccine available Avoid mosquito bites by using insect repellents, protective clothing and insecticides. Aedes mosquitoes bite during the day; particularly in the morning and late afternoon. Aedes mosquitoes are also indoor feeders and are often found in dark areas, It is advisable to spray these areas with insecticides. Do not to leave trash, pots, or any other containers outdoors, since they can fill with rainwater and become breeding grounds. No safe season Remind travelers that the symptoms of dengue may resemble those of malaria and that malaria should be ruled out first.

39 Reinfection Reinfection with another serotype of dengue virus may predispose a person to the development of dengue hemorrhagic fever or dengue shock syndrome, which is associated with a high mortality rate. Therefore, repeated travel to countries where dengue is endemic may put those previously infected with dengue travelers, immigrants, and persons visiting friends and relatives at increase risk.