1. Dr. Saleem Akhtar Rana Dr. Mahboob Ashraf Dr. Arshad Javaid Sh

2. KEY FACTS A mosquito-borne infection : No mosquito = no infection A severe flu-like illness Rarely a potentially lethal complication called dengue hemorrhagic fever (DHF) or Dengue Shock Syndrome (DSS). Global incidence of dengue has grown dramatically in recent decades. About two fifths of the world's population are now at risk. Dengue is found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban areas. Dengue hemorrhagic fever is a leading cause of serious illness and death among children in some Asian countries. No specific treatment; appropriate medical care saves the lives. 3. Virology &Transmission Aedes aegypti (albopictus) mosquitoes. After virus incubation for eight to 10 days, an infected mosquito is capable, during probing and blood feeding, of transmitting the virus for the rest of its life. (15-60 days) Infected female mosquitoes may also transmit the virus to their offspring by transovarial (via the eggs) transmission, but the role of this in sustaining transmission of the virus to humans has not yet been defined. Infected humans are the only hosts. The virus circulates in the blood of infected humans for two to seven days, at approximately the same time that they have a fever; Some studies have shown that monkeys in some parts of the world play a similar role in transmission. 4. Virology & Transmission Dengue infection is caused by anyone of 4 related, But antigenically distinct, viral serotypes: Dengue virus 1 (denv-1), dengue virus 2 (denv-2), dengue virus 3 (denv-3), and dengue virus 4 (denv-4); serotypes of dengue virus, RNA virus family flaviviridae, genus flavivirus. : Yellow fever, Hep C Recovery from infection by one provides lifelong immunity against that virus serotype But confers only partial and transient protection against subsequent infection by the other three viruses. There is good evidence that sequential infection increases the risk of developing DHF. 5. Immunization There is no vaccine to protect against dengue. With four closely related viruses that can cause the disease, the vaccine must immunize against all four types to be effective. Two vaccine candidates have advanced to evaluation in human subjects in countries with endemic disease, and several potential vaccines are in earlier stages of development. 6. Epidemiology An estimated 2.5-3 billion people in approximately 110 tropical and subtropical countries. Approximately 50-100 million people are infected with dengue. Less than 1 % , 250,000 individuals develop dengue hemorrhagic fever. Annually, approximately 500,000 individuals are hospitalized with the infection, and 24,000 deaths are attributed to dengue worldwide. Although initial epidemics were located in urban areas, increased dengue spread has involved suburban and rural locales in Asia and Latin America. 7. Factors For Increased Spread 1. Explosive population growth, 2. Unplanned urban overpopulation with inadequate public health systems(most Important) 3. Poor standing water and vector control, 4. Viral evolution, 5. Increased international recreational, business, and military travel to endemic areas. 8. PATHOPHYSIOLOGY During INCUBATION PERIOD (4-7 days, 3-14) Viral replication takes place in target dendritic cells. Infection of target cells, primarily those of the reticuloendothelial system, such as dendritic cells, hepatocytes, and endothelial cells, Result in the production of immune mediators that serve to shape the quantity, type, and duration of cellular and humoral immune response to both the initial and subsequent virus infections. FOLLOWING INCUBATION Due to chemical mediators ; A 5- to 7-day acute febrile illness ensues. Recovery is usually complete by 7-10 days. Dengue hemorrhagic fever or dengue shock syndrome usually develops around the third to seventh day of illness, approximately at the time of de-effervescence. 9. Patho-physiology Of DHG & DSS Most patients who develop dengue hemorrhagic fever or dengue shock syndrome have had prior infection with one or more dengue serotypes. These patients have two types of antibodies in their bodies. Neutralizing antibodies are present but not enough to eliminate the virus. Non-neutralizing antibodies result in antibody-antigen complexes which initiate damaging immune mechanisms. Circulating dengue antigen-antibody complexes, Activation of complement, Release of vasoactive amines. In the process of immune elimination of infected cells, proteases and lymphokines may be released and activate complement coagulation cascades and vascular permeability factors. Increased capillary permeability Increased capillary fragility Thrombocytopenia Increased coagulation parameters; PT, PTT. DAMAGE TO THE LIVER: Liver damage manifests as increases in levels of alanine aminotransferase and aspartate aminotransferase, low albumin level, resulting in severe fluid losses and bleeding. 10. Two Main End Results THE RAPID ONSET OF PLASMA LEAKAGE Plasma leakage is caused by increased capillary permeability and may manifest as hemoconcentration, as well as pleural effusion and ascites. USG can pick up thickening of GB wall due to edema in early stages and serial USG can be helpful to monitor the progress of plasma leakage. BLEEDING It can ranges from petechial skin hemorrhages , mild bleeding from gums or nose to life- threatening gastrointestinal bleeding. 11. Clinical Features: Two Types of populations; Two types of responses. Virgin Communities: Dengue Fever No previous exposure of the whole population. Mosquitoes are present; An infected person arrives and starts infection. Transmission appears to begin in urban centers and then spreads to the rest of a country. Infection rates may go up to 25-50 % of the population. Infection may be asymptomatic or symptomatic. This will be only flue like febrile illness with no DHF or DSS. This illness can be called Dengue Fever This is known as epidemic Dengue. This community will now harbour antibodies and be ready for second round of infection with possibility of DHF & DSS, if mosquitoes are not eliminated. Epidemic Transmission of Dengue Infection 12. Clinical features in already exposed communities; Hyper endemic Transmissions Breeding seasons of mosquitoes create seasonal variations. Infection and immunity is present in community. To be completely safe from infection, immunity against all four sero- types of virus is required; which is not present in all persons, especially children. Infection in non-immune persons, against all four types, will present as Dengue fever only. No danger of DHF & DSS. Infection in persons immune only against other than the infecting sero-type, may lead to life threatening DHF or DSS. So typical presentation of Dengue fever may lead to DHF & DSS. Hyper endemic Dengue Transmissions 13. Dengue infections In Pakistan (Majority = Asymptomatic) Asymptomatic 50-90 % Leaves behind Immunity only Dengue Fever Febrile illness of < 10 days. No consequence DHF & DSS