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Dengue virus belongs to family Flaviviridae, having four serotypes that spread by the bite of infected Aedes mosquitoes. It causes a wide spectrum of illness from mild asymptomatic illness to severe fatal dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Approximately 2.5 billion people live in dengue-risk regions with about 100 million new cases each year worldwide. The cumulative dengue diseases burden has attained an unprecedented proportion in recent times with sharp increase in the size of human population at risk. Dengue disease presents highly complex pathophysiological, economic and ecologic problems. In India, the first epidemic of clinical dengue-like illness was recorded in Madras (now Chennai) in 1780 and the first virologically proved epidemic of dengue fever (DF) occurred in Calcutta (now Kolkata) and Eastern Coast of India in 1963-1964. During the last 50 years a large number of physicians have treated and described dengue disease in India, but the scientific studies addressing various problems of dengue disease have been carried out at limited number of centres. Achievements of Indian scientists are considerable; however, a lot remain to be achieved for creating an impact. This paper briefly reviews the extent of work done by various groups of scientists in this country.

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.

Background & Objective: Dengue virus (DV) has caused severe epidemics of dengue fever (DF) and dengue haemorrhagic fever (DHF) and is endemic all over India. We have earlier reported that exposure of mice to hexavalent chromium [Cr(VI)] compounds increased the severity of dengue virus infection. Trivalent chromium picolinate (CrP) is used worldwide as micronutrient and nutritional supplement. The present study was therefore, carried out to investigate the effects of CrP on various haematological parameters during DV infection of mice., Methods: The Swiss Albino smice were inoculated with dengue virus (1000 LD50, intracerebrally) and fed with chromium picolinate (CrP) in drinking water (100 and 250 mg/l) for 24 wk. Peripheral blood leucocytes and other haematological parameters, and spleens were studied on days 4 and 8 after virus inoculations and the findings were compared with those given only CrP and the normal control age matched mice., Results: CrP in drinking water for 24 wk had no significant effects on peripheral blood cells of mice. On the other hand, there was significant decrease in different haematological parameters following inoculation of normal mice with DV. In CrP fed mice the effects of DV infection were abolished on most of the haematological parameters., Interpretation & Conclusion: The findings of present study showed that the adverse effects of DV infection, specially on platelets and leucocytes, were abrogated by pretreatment of mice with CrP. The therapeutic utility of CrP in viral infections including dengue needs to be studied in depth.

The present study was undertaken to investigate the spectrum of bacteria present in the River Gomti water before and after chlorination for drinking purposes. We observed that the strains of Pseudomonas aeruginosa that survived chlorination on three out of seven occasions were resistant to almost all the antibiotics tested. The chlorine-resistant bacteria had mucoid colonies and grew better at 24 degrees C. All attempts to isolate the plasmid responsible for chlorine resistance were unsuccessful. Laboratory experiments using different strains of the P. aeruginosa in distilled water showed that only the resistant strain survived chlorine treatment at a dose of < or =500 microg/L. Similar results were obtained when water collected from seven different sites on the River Gomti was treated with graded doses of chlorine. At the higher dose of chlorine, all the bacteria died in 30 min, whereas with lower doses all the bacteria survived. The present study underscores the importance of measuring water chlorine concentrations to assure they are sufficiently high to remove pathogenic bacteria from drinking water. To our knowledge, this is the first report in the literature of the selection of multidrug-resistant bacteria by suboptimal chlorine treatment of water.

This paper describes the clinical findings in 206 patients with dengue fever (DF) or with dengue hemorrhagic fever (DHF) during the epidemic of 1996 at Lucknow. The age group affected most was 11 to 30 years and 21% of the patients were less than 10 years old. The male:female ratio was 1.9:1. The onset was abrupt in all the patients, severe frontal headache was observed in 97%, myalgia in 90%, skin rash in 40%, vomiting in 29% and arthralgia in knee and hip joints in 9%. Anuria was seen in two patients. Lymphadenopathy was noted in 14%, hepatomegaly in 4%, being associated with mild jaundice in one patient, and splenomegaly in 2% of the patients. Involvement of the heart and lungs was seen in one patient each and no case with encephalitis was recorded. Hemorrhages from various sites were observed in 54% patients and 17 patients had profound shock. The commonest bleeding site was gums. Profound shock was preceded by various warning signs, the commonest being sudden hypotension. Among the patients with profound shock the mortality was 47% while the overall fatality rate was 3.8%. A number of the risk factors existed for a long time in this part of the world, but what precipitated the present epidemic at this time, is not known.

Dengue virus causes dengue fever, a mild febrile illness, and at times dengue hemorrhagic fever (DHF), a severe illness the pathogenesis of which is not fully understood. Given the crucial roles played by interleukin-8 (IL-8) as a chemoattractant cytokine and in inflammatory processes, levels of circulating IL-8 in the sera and IL-8 mRNA in the peripheral blood mononuclear cells (PBMC) were measured in 99 patients of a recent dengue epidemic that occurred in India in 1996 and in 21 normal healthy controls. Twenty-six of the patients had dengue fever (DF) and the remaining 73 were diagnosed as having different grades of DHF. All the control normal sera were negative for IL-8, so were their PBMC for IL-8 mRNA. Increased levels of IL-8 in the sera and IL-8 mRNA in their PBMC were observed in patients with severe illness of DHF grades III and IV. Only two out of 26 patients of DF and one out of 10 DHF grade I patient were positive for IL-8 and all three deteriorated to DHF grade IV within 24 hr. All six patients of DHF grade IV who died had higher serum level of IL-8 above 200 pg/ml, the highest being 5,568 pg/ml in one patient; the presence of mRNA for IL-8 was very high in all patients. A striking correlation was observed between increased levels of IL-8 and severe DHF, with greater levels in patients with increased grade of the disease and death. These results suggest that IL-8 may have an important role and may be an indicator of increasing severity of the disease and death.

Serum samples collected since 1989 with various patterns of reactivity for human immunodeficiency virus (HIV)-1, on the basis of screening ELISA and confirmatory Western blot (WB) test, were subjected to the detection of HIV-2 infection based on screening dot immunoassay and confirmatory WB for HIV-2. Significant prevalence of HIV-2 infection was (37.03%) among sera reactive for HIV-1 by ELISA but indeterminate by Western blot, compared with sera reactive for HIV-1 by ELISA and WB (3.29%) or negative by WB (2.63%). Out of 16 HIV-2 positive sera, 5 (31.25%) showed evidence of concomitant HIV-1 infection. This study demonstrates evidence of HIV-2 infection as early as 1989, earlier than reported so far from India.

From Sept. 1986 to Jan. 1989, a hospital-based study was conducted on 736 children, under 5 years of age, with acute respiratory infection. Nasopharyngeal secretions were examined for viruses by culture and by immunofluorescence. Viruses were detected in 22% of specimens: respiratory syncytial (5%), parainfluenza (5%), influenza A (4%), influenza B (2%), adenovirus (3%), measles (3%). The highest rates of detection were with patients diagnosed clinically as pneumonia or upper respiratory tract infection. The case fatality rate was very high (43%) in children with measles virus infection.

This communication reports the clinical features of 92 children with Japanese encephalitis diagnosed on the basis of viral isolation from brain or cerebrospinal fluid and/or a 4-fold or higher rise in antibody titre in paired sera by haemagglutination inhibition (HI) test, followed by detection of specific IgM HI antibody. More than a third of the patients (38%) were from urban areas. A high incidence of fever (94.5%), coma (100%) and convulsions (84.7%) was seen. Focal neurological deficit was found in 29.3 per cent of patients and pleocytosis in the cerebrospinal fluid in 32.3 per cent. An extrapyramidal syndrome developed in 21.3 per cent patients during the convalescent stage. Thirty four (36.9%) patients died while in hospital. Mortality was significantly related to a short prodromal stage, deep coma, abnormalities in tone and breathing and decerebrate posturing. Japanese encephalitis represents a severe disease in children with a high early mortality.

A total of 568 children suffering from acute respiratory infections were studied from September, 1986 to June, 1988 using indirect immunofluorescence technique to know the frequency of infections caused by parainfluenza viruses 1 and 3. Though sporadic cases of parainfluenza 1 (2.5%) and parainfluenza 3 (3.2%) were seen round the year, and increase in cases of parainfluenza virus type 1 infection was observed only in October, 1987 in Lucknow.

Two hundred and thirty children clinically diagnosed as suffering from acute respiratory infection were tested for four major groups of viral aetiological agents, i.e. influenza para-influenza, respiratory syncytial virus (RSV) and adenoviruses using indirect immunofluorescence technique. At least one of the respiratory viruses was identified in 51 (22 per cent) specimens, which included influenza A in 6 (3 per cent), influenza B in 3 (1 per cent), para-influenza type 1 in 3 (1 per cent), para-influenza type 3 in 13 (6 per cent), RSV in 11 (5 per cent) adenovirus in 12 (5 per cent), and dual virus infections in 3 (1 per cent) cases. Maximum number of virus identification was noted in children below 1 year of age, particularly infection with RSV followed by para-influenza and adenoviruses. Value of rapid diagnosis by indirect immunofluorescence technique is stressed.

In the present study rubella HI antibodies were determined in cases of congenital malformation and bad obstetric history to determine the role of rubella in such cases in India, as it has been reported to be rare in Japan in contrast to Western countries. The incidence of antibodies was statistically significant in cases of congenital eye, C.N.S., visceral and miscellaneous malformations and cases of spontaneous abortion and still-birth compared with controls of matching age groups. This is further supported by the demonstration of IgM antibodies in seven cases of congenital malformations and ten cases of spontaneous abortion. Our findings show that congenital rubella is not rare in India.

Eighty-six randomly selected children between 6 months and 12 years of age admitted with acute unexplained encephalopathy over a one year period were examined for evidence of Japanese encephalitis. One or more indicators of the infection were present in 36 (41.8%). Viral isolation from brain tissue was possible in 2 of 12 patients and from cerebrospinal fluid in 19 out of 62 patients. Serological evidence of probable Japanese encephalitis was found in 21 out of 36 patients. Japanese encephalitis is an important cause of acute childhood encephalopathy in the Lucknow area, where it is probably endemic.

A house to house survey was done from October 1972 to March 1974, covering 528952 individuals of urban population at Lucknow and 50,156 individuals of rural population of Unnao district, to find out the incidence of polio-like paralysis in our population. Among 12874 urban children up to 8 years old 8.2/1000 had polio-like paralysis while 4.6/1000 children of the rural population of 13554 children were affected. The incidence was significantly higher in the urban population. In the preschool age group almost 1 out of every 100 children was affected. A higher number of children were affected during 1968-9 and 1971-2, though it did not reach epidemic proportion. The findings show that paralytic polio is a serious problem in our country where poliomyelitis is endemic: this is contrary to the views generally held so far.

During a widespread epidemic of Japanese encephalitis, five pregnant women affected by the illness were observed. The diagnosis of Japanese encephalitis virus (JEV) infection was established on the basis of clinical presentation, rising titers of hemagglutination-inhibiting antibody, and the presence of specific IgM antibodies. Two women aborted, two were delivered of apparently normal children, and the fate of one case is not known. From brain, liver, and placental tissues of one of the aborted fetuses, JEV was isolated. This appears to be the first report of human transplacental infection with JEV.

A pandemic of acute haemorrhagic conjunctivitis occurred in south-east Asia during 1970 and 1971, and became epidemic in Lucknow in May 1971. From the conjunctival swabs adenovirus-like agents were isolated in monkey kidney tissue culture; one was typed as adenovirus 2. In paired sera rising antibody titres were found against an adeno-like agent isolated and the picornavirus (EC2/71) isolated in Singapore. The epidemics in south-east Asia were caused by a picornavirus while in Lucknow both adenovirus and picornavirus appeared to be implicated.

An epidemic of acute haemorrhagic conjunctivitis (AHC) recurred at Lucknow during July to September 1975, after a gap of 4 years. Out of the 35 cases investigated thoroughly, 20 Entero-70-like cytopathogenic agents were isolated from the conjunctiva which were neutralized by antisera against AHC virus J670/71 of Japan. Seroconversion was seen in 7 out of 11 paired sera from patients. Serological study was also done on 100 sera collected before the AHC epidemic of 1971, 100 sera after 1971 and 100 sera after 1975 epidemic. There were no neutralizing antibodies in the pre-epidemic period, while 18% of sera after the first epidemic and 32% after the second epidemic showed antibodies. The incidence of antibodies was highest (43%) in children aged below 10 years. Of the children born after the first epidemic, 44% had antibodies. Thus our findings show that the AHC virus appeared for the firt time at Lucknow in 1971 and the almost complete absence of disease in children, and its mildness during second epidemic, may be due to immunity.

An epidemic of febrile illness associated with haemorrhagic manifestations and shock occurred at Kanpur, India, during 1968. The epidemic was widespread in the city, involving about one-tenth of the population; cases were more frequent in thickly populated localities with poor sanitary conditions. Those affected were mainly adolescents and adults of both sexes and multiple cases occurred in families. The disease was characterized by the sudden onset of fever, associated with severe headache and low backache. A number of patients had bradycardia, vomiting and diarrhoea and macular skin rashes associated with itching. A small percentage of the patients had haemorrhagic manifestations in the form of haematemesis, haemoptysis, melaena, haematuria and bleeding per vaginum. The mortality was very low. Dengue type 4 virus has been implicated in the epidemic.

Several epidemics of febrile illnesses associated with haemorrhagic manifestations occurred in India during 1963 and 1964. These epidemics were restricted to the eastern coastal areas. However, in northern India, for the first time, a widespread epidemic of febrile illness associated with haemorrhagic manifestations occurred at Kanpur in 1968. In the present study, the virological findings of the epidemic are reported.The role of dengue type 4 virus in the epidemic is demonstrated by the isolation of the virus from a number of cases, including one with haematemesis, and conversion of antibody titres with dengue type 4 virus in the paired sera.