What is dengue fever?

Dengue fever is a disease caused by a family of viruses that are transmitted by mosquitoes. It is an acute illness of sudden onset that usually follows a benign course with symptoms such as headache, fever, exhaustion, severe muscle and joint pain, swollen glands (lymphadenopathy), and rash. The presence (the "dengue triad") of fever, rash, and headache (and other pains) is particularly characteristic of dengue. Other signs of dengue fever include bleeding gums, severe pain behind the eyes, and red palms and soles. Dengue (pronounced DENG-gay) strikes people with low levels of immunity. Because it is caused by one of four serotypes of virus, it is possible to get dengue fever multiple times. However, an attack of dengue produces immunity for a lifetime to that particular serotype to which the patient was exposed. Dengue goes by other names, including "breakbone" or "dandy fever." Victims of dengue often have contortions due to the intense joint and muscle pain, hence the name breakbone fever. Slaves in the West Indies who contracted dengue were said to have dandy fever because of their postures and gait. Dengue hemorrhagic fever is a more severe form of the viral illness. Manifestations include headache, fever, rash, and evidence of hemorrhage in the body. Petechiae (small red or purple blisters under the skin), bleeding in the nose or gums, black stools, or easy bruising are all possible signs of hemorrhage. This form of dengue fever can be life-threatening and can progress to the most severe form of the illness, dengue shock syndrome. Prevalence The global prevalence of dengue has grown dramatically in recent decades. The disease is now endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, South-East Asia and the Western Pacific (see Table 1). South-East Asia and the Western Pacific are most seriously affected. Before 1970 only nine countries had experienced DHF epidemics, a number which had increased more than four-fold by 1995. Some 2500 million people two fifths of the world's population - are now at risk from dengue. WHO currently estimates there may be 50 million cases of dengue infection worldwide every year. In 1998 alone, there were more than 616,000

cases of dengue in the Americas, of which 11,000 cases were DHF. This is greater than double the number of dengue cases which were recorded in the same region in 1995. Not only is the number of cases increasing as the disease is spreading to new areas, but explosive outbreaks are occurring. In Brazil nearly 475,000 cases were reported between January and October 1998 more than were reported from the entire continent in previous years.

Dengue distribution in 2006. Red: Epidemic dengue Some other statistics: During epidemics of dengue, attack rates among susceptibles are often 40 50%, but may reach 80 90%. An estimated 500 000 cases of DHF require hospitalisation each year, of whom a very large proportion are children and roughly 5% die. Without proper treatment, DHF case fatality rates can exceed 20%. With modern intensive supportive therapy, the rate can be reduced to less than 1%. The spread of dengue is attributed to expanding geographic distribution of the four dengue viruses and of their mosquito vectors, the most important of which is the predominantly urban species Aedes aegypti. A rapid rise in urban population is bringing ever greater numbers of people into contact with this vector, especially in areas which are favourable for mosquito breeding e.g.,

where household water storage is common and where solid waste disposal services are inadequate. Transmission Dengue viruses are transmitted to humans through the bites of infective female Aedes mosquitoes. Mosquitoes generally acquire the virus while feeding on the blood of an infected person. Once infective a mosquito is capable of transmitting the virus to susceptible individuals for the rest of its life, during probing and blood feeding. Infected femalemosquitoes may also transmit the virus to the next generation of mosquitoes by transovarial transmission i.e. via its eggs, but the role of this in sustaining transmission of virus to humans has not yet been delineated. Humans are the main amplifying host of the virus, although studies have shown that in some parts of the world monkeys may become infected and perhaps serve as a source of virus for uninfected mosquitoes. The virus circulates in the blood of infected humans for 2-7 days, at approximately the same time as they have fever; Aedes mosquitoes may acquire the virus when they feed on an individual at this time. Characteristics Dengue fever is a severe, flu-like illness that affects infants, young children and adults but rarely causes death. The clinical features of dengue fever vary according to the age of the patient. Infants and young children may have a non-specific febrile illness with rash. Older children and adults may have either a mild febrile syndrome or the classical incapacitating disease with abrupt onset and high fever, severe headache, pain behind the eyes, muscle and joint pains, and rash. Dengue haemorrhagic fever is a potentially deadly complication that is characterized by high fever, haemorrhagic phenomenaoften with enlargement of the liver

and

in

severe

cases,

circulatory

failure.

The illness commonly begins with a sudden rise in temperature accompanied by facial flush and other non-specific constitutional symptoms of dengue fever. The fever usually continues for 2-7 days and can be as high as 40-41 C, possibly with febrile convulsions and haemorrhagic phenomena. In moderate DHF cases, all signs and symptoms abate after the fever subsides. In severe cases, the patient's condition may suddenly deteriorate after a few days of fever; the temperature drops, followed by signs of circulatory failure, and the patient may rapidly go into a critical state of shock and die within 1224 hours, or quickly recover following appropriate volume replacement therapy.

Mechanism

When a mosquito carrying dengue virus bites a person, the virus enters the skin together with the mosquito's saliva. It binds to and enters white blood cells, and reproduces inside the cells while they move throughout the body. The white blood cells respond by producing a number of signaling proteins, such as interferon, which are responsible for many of the symptoms, such as the fever, the flu-like symptoms and the severe pains. In severe infection, the virus production inside the body is greatly increased, and many more organs (such as the liver and the bone marrow) can be affected, and fluid from the bloodstream leaks through the wall of small blood vessels into body cavities. As a result, less blood circulates in the blood vessels, and the blood pressure becomes so low that it cannot supply sufficient blood to vital organs. Furthermore, dysfunction of the bone marrow leads to reduced numbers of platelets, which are necessary for effective blood clotting; this increases the risk of bleeding, the other major complication of dengue Viral reproduction Once inside the skin, dengue virus binds to Langerhans cells (a population of dendritic cells in the skin that identifies pathogens). The virus enters the cells through binding between viral proteins and membrane proteins on the Langerhans cell, specifically the C-type lectins called DC-SIGN, mannose receptor and CLEC5A.[12] DC-SIGN, a non-specific receptor for foreign material on dendritic cells, seems to be the main point of entry. The dendritic cell moves to the nearest lymph node. Meanwhile, the virus genome is replicated in membrane-bound vesicles on the cell's endoplasmic reticulum, where the cell's protein synthesis apparatus produces new viral proteins, and the viral RNA is copied. Immature virus particles are transported to the Golgi apparatus, the part of the cell where some of the proteins receive necessary sugar chains (glycoproteins). The now mature new viruses bud on the surface of the infected cell and are released by exocytosis. They are then able to enter other white blood cells, such as monocytes and macrophages. The initial reaction of infected cells is to produce interferon, a cytokine that raises a number of defenses against viral infection through the innate immune system by augmenting the production of a large group of proteins mediated by

the JAK-STAT pathway. Some serotypes of dengue virus appear to have mechanisms to slow down this process. Interferon also activates the adaptive immune system, which leads to the generation of antibodies against the virus as well as T cells that directly attack any cell infected with the virus. Various antibodies are generated; some bind closely to the viral proteins and target them for phagocytosis (ingestion by specialized cells and destruction), but some bind the virus less well and appear instead to deliver the virus into a part of the phagocytes where it is not destroyed but is able to replicate further. Treatment There is no specific treatment for dengue fever. However, careful clinical management by experienced physicians and nurses frequently save the lives of DHF patients. With appropriate intensive supportive therapy, mortality may be reduced to less than 1%. Maintenance of the circulating fluid volume is the central feature of DHF case management. Immunization Vaccine development for dengue and DHF is difficult because any of four different viruses may cause disease, and because protection against only one or two dengue viruses could actually increase the risk of more serious disease. Nonetheless, progress is gradually being made in the development of vaccines that may protect against all four dengue viruses. Such products could be commercially available within several years. Prevention and Control At present, the only method of controlling or preventing dengue and DHF is to combat the vector mosquitoes. In Asia and the Americas, Aedes aegypti breeds primarily in man-made containers like earthenware jars, metal drums and concrete cisterns used for domestic water storage, as well as discarded plastic food containers, used automobile tyres and other items that collect rainwater In Africa it also breeds extensively in natural habitats such as tree holes and leaf axils. In recent years, Aedes albopictus, a secondary dengue

vector in Asia, has become established in the United States and several Latin American and Caribbean countries as well as two European and one African state. The rapid geographic spread of this species has been largely attributed to the international trade in used tyres. Vector control is implemented using environmental management and chemical methods. Proper solid waste disposal and improved water storage practices, including covering containers to prevent access by egg laying female mosquitoes are among methods which are encouraged through community-based programmes. The application of appropriate insecticides to larval habitats, particularly those which are considered useful by the householders, e.g. water storage vessels, prevent mosquito breeding for several weeks but must be re-applied periodically. Small, mosquito-eating fish have also been used with some success. During outbreaks, emergency control measures may also include the application of insecticides as space sprays to kill adult mosquitoes using portable or truck-mounted machines or even aircraft. However, the killing effect is only transient, variable in its effectiveness because the aerosol droplets may not penetrate indoors to microhabitats where adult mosquitoes are sequestered, and the procedure is costly and operationally very demanding. Regular monitoring of the vectors' susceptibility to the most widely used insecticides is necessary to ensure the appropriate choice of chemicals. Active monitoring and surveillance of the natural mosquito population should accompany control efforts in order to determine the impact of the programme.

Dengue

fever

in

Bangladesh
Bangladesh First outbreak of dengue fever (Dhaka fever) was documented in 1964 in Dhaka followed by few 7

scattered cases of DF during 1977-78. In 1996-97 dengue infections were confirmed in 13.7% of 255 fever patients screened at Chittagong Medical College. The first epidemic of dengue haemorrhagic fever occurred in mid 2000, when 5 551 dengue infections were reported from Dhaka, Chittagong and Khulna cities, occurring mainly among adults. Among the reported cases 4 385 (62.4%) were dengue fever infections and 1 186 (37.6%) cases were dengue haemorrhagic fever. The case fatality rate was 1.7% with 93 deaths reported. Aedes aegypti was identified as the main vector responsible for the epidemic and Aedes albopictus was identified as a potential vector in Chittagong. National Guidelines for the Clinical Management of Dengue Syndrome have been developed, based on the established WHO guidelines, and distributed among medical officers in the country. The worst outbreak was in 2002 with 6,104 cases and 58 deaths. In 2004, a total of 3,934 cases with 13 deaths (CFR = 0.33%) were reported. The epidemic started in June (143), peaked in July (1,209) and continued in August (818). During the outbreak period, 98% of the cases were from Dhaka with a case fatality rate of 2.3%. The rest of the cases were from districts of Khulna, Jessore, Barishal, Comilla, Chittagong, Jhinaidah, Sirajgonj, and Madaripur. Bangladesh has been experiencing many outbreaks of dengue since 1999. In 2005 there are 1048 reported cases and 4 deaths (CFR 0.38%). The number cases and deaths reduction is about 73 % and 69% as compared to 2004. In 2006 the number of cases and deaths has increased by 2 fold as compared to 2005. The maximum transmission period is July to September each year since 2000. During January 2000December 2007, Bangladesh recorded a total of 22 245 cases and 233 deaths (1.04%). Of these, Dhaka accounted for 20 115 cases and 181 deaths (0.9%). In the absence of a vaccine and specific treatment available for dengue, vector control remains the only option. Early warning about the disease based on forecasting, therefore, becomes crucial for the prevention and control of dengue in Bangladesh. The time series analyses methodology has been increasingly used in the field of 8

epidemiological

research

on

infectious

diseases,

particularly

in

the

assessment of health services. In health science research,Autoregressive Integrated Moving Average (ARIMA) models[12-18] as well as Seasonal Autoregressive Integrated Moving Average (SARIMA) models are useful tools for analysing time series data containing ordinary or seasonal trends to develop a predictive forecasting model. There have been efforts in forecasting dengue incidence in different parts of the world using both ARIMA and SARIMA modelling. This study is aimed at developing univarite time series models to forecast the monthly dengue incidence in Dhaka based on reported monthly cases available from 20002007. This forecasting offers the potential for improved and consistent planning of public health interventions. (Ref: Forecasting dengue incidence in Dhaka, Bangladesh: A time series analysis (ICDDR,B), M.A.H. Zamil Choudhurya, Shahera Banub,)

Reference:
1. Rigau-Perez JG, Clark GC, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV. Dengue and dengue haemorrhagic fever. Lancet. 1998 Sept 19; 352(9132): 971-977. 2. Gaidamovich SY, Siddiqi SM, Haq F, Klisenko GA, Melnikova EE, Obukhova VR. Serological evidence of dengue fever in the Bangladesh Republic. Acta Virol. 1980; 24: 153. 3. Catalano R, Serxner S. Time series designs of potential interest to epidemiologists. Am Epidemiol. 1987; 126: 724-731. 4. http://www.who.int/en/ 5. http://www.whoban.org/en/Section29.htm