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GUEST EDITORIAL
Year : 2004  |  Volume : 22  |  Issue : 1  |  Page : 5-6
 

Dengue haemorrhagic fever: A global challenge


Industrial Toxicology Research Centre, Mahatma Gandhi Marg, Luncknow - 226 001, India

Correspondence Address:
Industrial Toxicology Research Centre, Mahatma Gandhi Marg, Luncknow - 226 001, India



How to cite this article:
Chaturvedi U C, Shrivastava R. Dengue haemorrhagic fever: A global challenge. Indian J Med Microbiol 2004;22:5-6


How to cite this URL:
Chaturvedi U C, Shrivastava R. Dengue haemorrhagic fever: A global challenge. Indian J Med Microbiol [serial online] 2004 [cited 2019 Sep 22];22:5-6. Available from: http://www.ijmm.org/text.asp?2004/22/1/5/8054


Dengue haemorrhagic fever (DHF) is back once again. Prior to 1970 only nine countries had experienced DHF epidemics. The 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, Southeast Asia and the Western Pacific. Southeast Asia and the Western Pacific are most seriously affected. Some 2500 million people - two fifths of the world's population - are now at risk from dengue. WHO currently estimated 50 million cases of dengue infection worldwide every year. During epidemics of dengue, attack rates among susceptibles are 40 to 90%. An estimated 500,000 cases of DHF require hospitalization each year, of whom a very large proportion are children.[1],[2] The year 2001 witnessed unprecedented global dengue epidemic activity in the American hemisphere, the Pacific islands and continental Asia. During 2002, more than 30 Latin American countries reported over 1,000,000 dengue fever cases with large number of DHF cases. This has been followed by extensive epidemics of DHF in several parts of India during 2003.
Dengue is a mosquito borne virus infection which is found in tropical and subtropical regions around the world, predominantly in urban and semiurban and now in rural areas. Dengue is caused by four distinct viruses (type 1 to 4) that are closely related antigenically. Humans are the main amplifying host of the virus. Recovery from infection provides lifelong immunity against that serotype but confers only partial and transient protection against subsequent infection by the other three. It has been suggested that sequential infection increases the risk of more serious disease resulting in DHF.
The Indian encounter with dengue and DHF is interesting and intriguing. The first major epidemic illness compatible clinically with dengue occurred in Madras in 1780 which later spread to all over the country. The dengue virus was first isolated in Japan in 1943 but the one isolated at Calcutta in 1944 from the blood of US soldiers was considered as a first report for a long time. DHF, a potentially lethal complication of dengue virus infection, was first recognized in the 1950s during the dengue epidemics in the Philippines and Thailand and quickly spread to other parts of the World.[3] Today DHF affects most Asian countries and has become a leading cause of hospitalization and death among children in several of them. The risk factors for DHF are infestation with Aedes mosquito, hot and humid climate enhancing mosquito breeding, mosquito density, and presence of all the four serotype of the dengue virus with secondary infection in the host, the water storage pattern in the houses, population density and large movement of people towards urban areas. While DHF was present in the neighbouring countries for a long time it was not known why India was not affected since all the risk factors were present in this country. When the first extensive epidemic of DHF occurred during 1996 in Northern India, there was no clue of its emergence.
The 1996 epidemic in India was mainly due to dengue type 2 virus[4] while the 2003 epidemic appears to be mainly due to dengue type 3 virus. Over the past two decades, dengue virus type 3 (DV-3) has caused unexpected epidemics of DHF in Sri Lanka, East Africa and Latin America. Isolates from these geographically distant epidemics are closely related and belong to DV-3, subtype III, which originated in the Indian subcontinent. The emergence of DHF in Sri Lanka in 1989 correlated with the appearance of a new DV-3, subtype III variant. This variant most likely spread from the Indian subcontinent into Africa in the 1980s and from Africa into Latin America in the mid-1990s. DV-3, subtype III isolates from mild and severe disease outbreaks form genetically distinct groups.[5] Which suggests a role for viral genetics in DHF. There is need to genotype the dengue viruses isolated from the different parts of this country and study their relationship. At the same time human leukocyte antigen alleles correlate with both protection and susceptibility to DHF and dengue shock syndrome. Studies in Haiti suggest that blacks have a gene providing nearly complete protection against severe dengue illness.
Early diagnosis of dengue virus infection is important and can be established with easily available laboratory tests. But what is the value and appropriate use of the tourniquet test in dengue? A negative test does not rule out dengue infection, a positive test should be followed by close surveillance for early signs of DHF. Low platelet counts do not predict clinically significant bleeding in dengue. It follows that platelet or blood transfusions should not be administered based upon platelet count alone. DHF or dengue shock syndrome cases frequently have compensated consumptive coagulopathy that seldom requires treatment. Bleeding is most likely caused by activated platelets resulting from damaged capillary endothelium. There is no specific treatment for dengue fever. However, careful clinical management frequently saves 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.
Viral virulence and immune responses have been considered as two major factors responsible for the pathogenesis of DHF. Virological studies are attempting to define the molecular basis of viral virulence. The immunopathological mechanisms appear to include a complex series of immune responses. A rapid increase in the levels of cytokines and chemical mediators apparently plays a key role in inducing plasma leakage, shock and haemorrhagic manifestations.[2],[6] It is likely that the entire process is initiated by infection with a so-called virulent dengue virus, often with the help of enhancing antibodies in secondary infection, and then triggered by rapidly elevated cytokines and chemical mediators produced by intense immune activation. The co-circulation of multiple dengue virus serotypes in the same region has been a common knowledge in several countries including India. Using a modified multiplex reverse transcription-polymerase chain reaction assay, concurrent infections by two different serotypes of dengue virus have been shown to occur in the same patient. Such concurrent infections by two dengue viruses may also increase the severity of the disease. However, understanding of the DHF pathogenesis is far from complete.
Vaccine development for dengue and DHF is difficult because any of the 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. However, effort is being made to develop vaccines that may protect against all four dengue viruses. Several promising vaccine candidates in the form of live attenuated and chimeric vaccines have been developed and are currently in human clinical trials. However, significant practical, logistic, and scientific challenges remain before these vaccines can widely and safely be applied to vulnerable populations.
At present, the only method of controlling or preventing dengue and DHF is to combat the vector mosquitoes. 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. It can also breed 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, several Latin American and Caribbean countries, in parts of Europe and in one African country. The rapid geographic spread of this species has been largely attributed to the international trade in used tyres.
Dengue continues to be a global challenge because the pathogenesis of DHF is not fully understood, there is no immediate prospect of a vaccine and the mosquito control measures are inadequate. The wide spread DHF epidemics during 2003 reinforces the belief that DHF has come to stay in this country and will continue to spread to newer areas unless vector control measures are taken up on war footing. 

 ~ References Top

1.Halstead SB. Dengue. Curr Opin Infect Dis 2002;15:471-476.  Back to cited text no. 1    
2.Chaturvedi UC, Raghupathy R, Pacsa AS, Elbishbishi EA, Agarwal R, Nagar R, Misra A, Kapoor S, Mathur A, Khan MAY, Azizieh F. Shift from a Th1-type response to Th2-type in dengue haemorrhagic fever. Curr Sci 1999;76:63-69.  Back to cited text no. 2    
3.Gubler DJ. Dengue and dengue hemorrhagic fever: its history and resurgence as a global public health problem. In "Dengue and dengue hemorrhagic fever" Eds. DJ Gubler, GK Kuno. CAB International, New York, 1997:1-22.  Back to cited text no. 3    
4.Agarwal R, Kapoor S, Nagar R, Misra A, Tandon R, Mathur A, Misra AK, Srivastava KL, Chaturvedi UC. A clinical study of the patients with dengue haemorrhgic fever during the epidemic of 1996 at Lucknow, India. Southeast Asian J Trop Med Publ Hlth 1999;30:735-740.  Back to cited text no. 4    
5.Messer WB, Gubler DJ, Harris E, Sivananthan K, de Silva AM. Emergence and global spread of a dengue serotype 3, subtype III virus. Emerg Infect Dis 2003;9:800-809.  Back to cited text no. 5    
6.Chaturvedi UC, Agarwal R, Elbishbishi EA, Mustafa AS. Cytokine Cascade in Dengue Haemorrhagic Fever: Implications for Pathogenesis. FEMS Immunol Med Microbiol 2000;28:183-188.  Back to cited text no. 6    
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2004 - Indian Journal of Medical Microbiology
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