Dengue Viral Infection And Risk Of An Epidemic Biology

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Dengue is an arbovirus disease caused by four dengue virus serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) and transmitted to humans by mosquito as a vector.

2.1.1 History overview

It was believed that dengue viral infection has a long history. First reported cases that were believed to be dengue-like syndrome were recorded in China in 992 AD. They were followed by the sporadic outbreaks in the French West Indies in 1935 and in Panama in 1699. However, the major epidemics of illness believed to be dengue were reported in Asia, Africa and North America in 1779 and 1780 (6). At that time, the etiology was not clear until researchers enabled to isolate and characterize the dengue viruses in laboratory during World War II. So dengue transmission before 1940 was characterized by infrequent, mostly sporadic cases and uncertainty of etiology. The transmission increased significantly in Southeast Asia and Pacific during and after World War II when the ecology disruption and demographic changes occurred. The condition after World War II was suitable for the transmission and the co-circulation of multiple dengue virus serotypes. As a result, Dengue Hemorrhagic Fever (DHF) emerged in this region. The first epidemic of DHF occurred in Manila, Philippines (1953 to 1954), was followed by Bangkok, Thailand (1958) and Malaysia, Singapore and Vietnam (1960) and spread to the whole region during the 1970s. In addition, the transmission spread further to other regions in Asia: westward to India, Sri Lanka, Maldives and Pakistan and eastward to China. The number of epidemic also increased in the Pacific Islands in 1970s. Therefore, DHF became a major public-health problem in South East Asia regions and wide spread in the Asian continent.

Yet, the transmission was slightly different from what happened in America and Africa. In the former continent, the epidemic of dengue was rare from 1950s until 1970s due to the successful eradication of A. aegypti, the principal vector, from most of Central and South America. However, control programs were not sustained and there were re-infestation of the mosquito. As a result, the major epidemics of dengue occurred , first in Cuba in 1981, after it had been free from this disease for over three decades (7). Annual cases have been reported almost every year since this moment. Up to now, more than thirty countries in America reported dengue cases and multiple dengue serotypes circulate in this region. In addition, the total number of DHF cases reached to 106,037 and the case fatality was 1.2% from 2001 to 2007 (1). Speaking about DF/DHF in Africa, there is little information due to poor dengue surveillance. However, epidemic DF caused by all four dengue serotypes has increased since 1980 with which the most epidemics occurred in the eastern Africa and to a smaller extent in the western Africa (1).

The emergence of the epidemic DF/DHF as a global public health problem related to some factors, such as global population growth, unplanned and uncontrolled urbanization with substandard living conditions, lack of vector control, virus evolution, international traveling, changing in public health policy, inadequate water supply, disparity and poor sanitation (7-10). Of all these factors, urbanization has probably had the most impact on the amplification of dengue within a given country, and international traveling has had the most impact for the spread of dengue from country to country and continent to continent (10).

Furthermore, the pattern of the disease observed varies across places and time. Seasonality and cyclical patterns were presence in a majority of endemic countries. In general, the epidemics occur every three to five years. It is perhaps due to the combination of demographic, immunologic and environmental changes. Besides this, climatic factors, such as the El Niňo Southern Oscillation (ENSO) and global warming may have contributions to the cyclical pattern of dengue activity (10, 11).

2.1.2 Burden of disease

In the last fifteen years, Dengue/DHF has widely accepted as the most important arthropod borne viral disease of humans. The incidence have increased thirty folds with hyper endemic transmission expanding geographically to new countries, from urban to rural setting as shown in Figure 2.1.

Source: WHO. Dengue: guidelines for diagnosis, treatment, prevention and control, 2009

Figure 2.1 Areas at risk of dengue transmission, 2008

The disease burdens are intense among countries in South-East Asia and the Western Pacific. However dengue fever and DHF/DSS were endemic as well in Africa, America and The Eastern Mediterranean, particularly in tropical and sub tropical countries. (12). Over 100 countries reported this disease and approximately 2.5 to 3 billion people live in these endemic areas. It is estimated that 50 million infections occur annually, including DHF cases and deaths which are respectively 500,000 and 21,000 (9). Moreover, the wide spread of the transmission can be observed also from the countries reporting cases to WHO. During nine years from 1970 to1979, only nine countries in the world had dengue epidemics, but twenty years later the number of affected countries had increased more than four times. The average number of DHF cases which were reported to WHO had increased dramatically from 908 in the 1950s to 925,896 in the period of 2000 - 2007, as described in Figure 2.2 (1, 12). While the case fatality rate (CFR) varies among countries, less than 1% in some but can be as high as 10-15% (2).

Source: WHO. Dengue: guidelines for diagnosis, treatment, prevention and control, 2009

Figure 2.2 Average number of DF/DHF cases reported to WHO and countries reporting dengue 1955 - 2007

Dengue inflicts a significant health, economic and social burden in endemic areas (1). Children mostly suffer from DHF/DSS, with the average hospital stays of 5-10 days for severe cases. There are both direct and indirect costs for each dengue patient, from inconvenience with uncomplicated DF to costs for hospitalization and significant disruption of earning potential. In addition, there are costs to local municipalities for vector control activities, and often revenue lost through reduced tourism (13). Globally the estimated number of disability-adjusted-like-years (DALYs) lost to dengue in 2001 was 528 (1). Prospective studies on the cost of dengue cases in eight countries in America and Asia found that the overall mean costs were $514 for an ambulatory and $1,394 for hospitalized cases. With an annual average of 574,000 cases reported, the aggregate annual economic cost of dengue for the eight study countries in Asia and America is at least $587 million. Preliminary adjustment for under-reporting it could raise this total up to $1.8 billion, and incorporating costs of dengue surveillance and vector control would raise the amount further. Dengue imposes substantially financial burden on both the health sector and the overall economy (14).

2.1.3 Dengue in South-East Asia and Western Pacific Regions

Approximately 1.8 billion (more than 70%) of population at risk for dengue live in South-East Asia and Western Pacific Regions (1). After first being recognized as DHF in the Philippines in 1953, the mean number of annual cases of DHF has increased from below 10,000 in the period of 1950-1960 to 46,458 and 188,684 in 1986 and 2006, respectively. The trend of reported cases is rising, whereas the case fatality rate is maintained below 1% (4, 15), as shown in Figure 2.3.


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