Co-positivity of anti-dengue virus and anti-Japanese encephalitis virus IgM in endemic area: co-infection or cross reactivity?

OBJECTIVE: To report high co-positivity of anti-dengue virus (DV) and anti-Japanese encephalitis virus (JEV) IgM in an area endemic for both the viruses and to discuss the possibilities of co-infection. METHODS: Serum samples from the patients who presented with fever, suspected central nervous system infection and thrombocytopenia, were tested for anti-DV IgM and anti-JEV IgM antibodies. Conventional reverse transcriptase polymerase chain reaction was done for detection of DV RNA and JEV RNA. RESULTS: Of 1 410 patient sera tested for anti-DV and anti-JEV antibodies, 129 (9.14%) were co-positive for both. This co-positivity was observed only in those months when anti-JEV IgM positivity was high. Titers of both anti-DV IgM and anti-JEV IgM were high in most of the co-positive cases. Among these 129 co-positive cases, 76 were tested by conventional reverse transcriptase polymerase chain reaction for both flaviviruses, of which eight cases were co-positive for DV and JEV. CONCLUSIONS: Co-infection with more than one flavivirus species can occur in hyperendemic areas.

Trend of dengue virus infection at Lucknow, north India (2008- 2010): a hospital based study.

BACKGROUND & OBJECTIVES: Dengue virus (DV) infection has emerged as a major health problem in north India. Here, we report the annual trend of dengue virus infection as seen in Lucknow, Uttar Pradesh, during 2008-2010. METHODS: Blood samples from clinically suspected cases of dengue virus infection were collected and history was taken on structured clinical data sheet. All samples were tested for dengue IgM by antibody capture ELISA. Selected samples were tested by conventional RT-PCR for dengue virus RNA. Weather information was continuously recorded from website of world weather information service . RESULTS: There was a gradual increase in number of dengue fever cases with increased occurrence in 2010. Cases referred in January - December 2008 were 398 (54.5% anti DV IgM positive), in January - December 2009 were 599 (51.9% anti DV IgM positive) and in January - December 2010 were 1602 (64.9% anti DV IgM positive). Serotypes circulating in years 2008, 2009 and 2010 were DV-2 & DV-3, DV -1, 2 & 3 and DV-1 and DV-2 respectively. There is no statistical significant correlation between weather data and increasing dengue positive cases. INTERPRETATION & CONCLUSIONS: Increased cases of dengue fever were seen in 2010, which was not correlated with any change in environmental factors. A change in circulating serotypes was noted.

Nitric oxide in dengue and dengue haemorrhagic fever: necessity or nuisance?

Advances in free radical research show that reactive oxygen and nitrogen oxide species, for example superoxide, nitric oxide (NO) and peroxynitrite, play an important role in the pathogenesis of different viral infections, including dengue virus. The pathogenic mechanism of dengue haemorrhagic fever (DHF) is complicated and is not clearly understood. The hallmarks of the dengue disease, the antibody-dependent enhancement, the shift from T-helper type 1 (Th1) to Th2 cytokine response and the cytokine tsunami resulting in vascular leakage can now be explained much better with the knowledge gained about NO and peroxynitrite. This paper makes an effort to present a synthesis of the current opinions to explain the pathogenesis of DHF/shock syndrome with NO on centre stage.

Dengue and dengue haemorrhagic fever: Indian perspective.

The relationship of this country with dengue has been long and intense. The ?rst recorded epidemic of clinically dengue-like illness occurred at Madras in 1780 and the dengue virus was isolated for the ?rst time almost simultaneously in Japan and Calcutta in 1943-1944. After the ?rst virologically proved epidemic of dengue fever along the East Coast of India in 1963-1964, it spread to allover the country.The ?rst full-blown epidemic of the severe form of the illness,the dengue haemorrhagic fever/dengue shock syndrome occurred in North India in 1996. Aedes aegypti is the vector for transmission of the disease. Vaccines or antiviral drugs are not available for dengue viruses; the only effective way to prevent epidemic degure fever/dengue haemorrhagic fever (DF/DHF) is to control the mosquito vector, Aedes aegypti and prevent its bite. This country has few virus laboratories and some of them have done excellent work in the area of molecular epidemiology,immunopathology and vaccine development. Selected work done in this country on the problems of dengue is presented here.

Dengue virus-specific suppressor T cells: current perspectives.

Dengue virus was the first microorganism that was shown to induce generation of antigen-specific suppressor T (TS) cells in mice. The cascade of the three generations of TS cells (TS1, TS2, TS3) and their secretary products, the suppressor factors (SF1, SF2), was delineated. The TS pathway was proposed to be protective through inhibition of the production of enhancing antibody, which may enhance the severity of dengue disease. The currently second most favoured mechanism of severe dengue disease is the 'cytokine tsunami'. During the last decade, suppressor/regulatory T cells have been studied in greater detail using modern techniques in various diseases, including viral infections. This brief review discusses the role of dengue-specific suppressor T cells in protection and/or induction of severe dengue disease in view of our current understanding of suppressor/regulatory T cells.

Macrophage and dengue virus: friend or foe?

The cells of monocyte-macrophage (Mphi) lineage play important roles both in innate and adaptive immune responses. They are the first line of defence in body and their job is to phagocytose a foreign invader, the pathogen, digest it and remove it. Mphi help body in mounting the antigenspecific immune response by presenting the digested pathogen antigen in conjunction with major histocompatibility complex (MHC) class II molecules to recruit B and T lymphocytes response. Usually Mphi succeed in their job of eliminating most pathogens from the body but sometimes the pathogen strikes a "friendship" with them and starts using them for its benefit. A number of pathogens, including dengue virus (DV), subvert Mphi and use them for their replication, increasing the severity of damage to the body. This duality may be related to the fact that Mphi serve as efficient host cell for DV replication, in addition to being responsible for innate immunity and for initiating adaptive immune responses. This review gives a brief overview of the various roles of Mphi (enmity and friendship) during dengue virus infection.

Dengue and dengue haemorrhagic fever: implications of host genetics.

Little is known of the role of human leucocyte antigen (HLA) alleles or non-HLA alleles in determining resistance, susceptibility or the severity of acute viral infections. Dengue fever (DF) and dengue haemorrhagic fever (DHF) are suitable models for immunogenetic studies, yet only superficial efforts have been made to study dengue disease to date. DF and DHF can be caused by both primary and secondary infection by any of the four serotypes of the dengue virus. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virus virulence. Variations in immune response, often associated with polymorphism in the human genome, can now be detected. Data on the influence of human genes in DF and DHF are discussed here in relation to (1) associations between HLA polymorphism and dengue disease susceptibility or resistance, (2) protective alleles influencing progression to severe disease, (3) alleles restricting CD4(+) and CD8(+) T lymphocytes, and (4) non-HLA genetic factors that may contribute to DHF evolution. Recent discoveries regarding genetic associations in other viral infections may provide clues to understanding the development of end-stage complications in dengue disease. The scanty positive data presented here indicate a need for detailed genetic studies in different ethnic groups in different countries during the acute phase of DF and DHF on a larger number of patients.

Dengue vaccines: problems and prospects.

The extent of cumulative disease burden caused by dengue virus has attained an unprecedented level in recent times with sharp increase in the size of human population at risk. Dengue disease presents highly complex medical, economic and ecologic problems. The surge in publications on the development of dengue vaccines, taking advantage of new generation of biotechnology techniques indicates the profound interest and urgency in the scientific and medical communities in combating this disease. This review summarizes the importance of critical subjects like pathogenesis of dengue haemorrhagic fever and inadequacy of animal model that have adversely affected dengue vaccine development. Further, the remarkable progresses so far made in dengue vaccine research not only employing a diverse range of new strategies but also re-using old techniques to improve the existing vaccines, have been presented. The efficacy and safety of some of the new vaccine candidates have been evaluated and proven in human preclinical/clinical trials. Besides the technical advancement in vaccine development, vaccine safety and vaccine formulation have been examined.