Investigation of apoptotic markers among human immunodeficiency virus (HIV-1) infected individuals.

BACKGROUND & OBJECTIVES: Apoptosis causes a decline in the counts of uninfected bystander CD4+ T cells in HIV infection. The rate of disease progression of HIV infection is considered to be faster in the developing countries. The present study was carried out to investigate certain markers for apoptosis in immunopathogensis of disease in HIV infected south Indian population. METHODS: Soluble Fas (sFas) antigen and Fas ligand levels in plasma samples from 39 antiretroviral treatment naïve patients was estimated and compared with T cell subsets and HIV-1 viral load. RESULTS: The mean sFas antigen levels among controls and the CDC A, B and C clinical stages were 2.77, 3.08, 3.26 and 3.28 ng /ml respectively, higher though not significantly among HIV-1 infected individuals compared to controls. The mean sFas ligand levels in CDC A, B and C stages were 0.138, 0.125 and 0.117 ng/ml respectively were higher (P<0.001) than controls (0.073 ng/ml) and positively correlated with total lymphocyte % (r=0.43, P =0.007). sFas antigen levels were negatively correlated with total WBC count (r=-0.34, P=0.04), CD4% (r=-0.4, P=0.01) and CD4:CD8 ratio (r=-0.37, P=0.02). There was an increase in plasma levels of sFas antigen and Fas ligand over time in asymptomatics. INTERPRETATION & CONCLUSION: The high levels of sFas antigen and Fas ligand seen in HIV infected individuals suggest increased activation and apoptosis of T cells, due to constant stimulation of the immune system by inter-current infections of HIV infected individuals in south India.

Correlation between hepatitis B genotypes, 1896 precore mutation, virus loads and liver dysfunction in an Indian population.

BACKGROUND/OBJECTIVES: Hepatitis B virus (HBV) genotypes may differ in pathogenicity. However, the interplay between different virus characteristics such as genotypes, mutants and virus loads has not been well studied . We investigated the association between HBV genotype, presence of 1896 precore mutation and HBV viral loads in patients with HBV-related liver disease. METHODS: One hundred and sixteen HBV DNA-seropositive patients attending a gastroenterology outpatient clinic and 107 HBV DNA-seropositive blood donors were recruited. The subjects were stratified as those with normal (Group I, n=164) and elevated (Group II, n=59) ALT levels. The HBV genotype and the presence of the 1896 precore mutation were determined, and plasma HBV DNA levels measured. RESULTS: Genotype C was more common in Group II than in Group I (10 (17%) vs. 4 (2.4%); p< 0.005). There was no relationship between the 1896 precore mutation and the HBV DNA levels. Subjects with genotype C (n=14) had higher HBV DNA levels than those with genotypes A (n=33) or D (n=158). CONCLUSIONS: The infecting genotype, but not the presence of 1896 precore mutation, correlates with HBV load. The association of genotype C with higher virus loads and with elevated ALT may point to a greater pathogenicity of this genotype.

Chemokine profile among human immunodeficiency virus-1 (HIV-1) infected individuals from southern India.

BACKGROUND & OBJECTIVE: Individuals infected with HIV-1 have higher levels of chemokine producing cells compared to uninfected individuals. It is important to know the changes in chemokine levels associated with rate of progression of disease. There is a paucity of information on the plasma chemokines in HIV-1 infected individuals from India. We therefore carried out this study to estimate the levels of three chemokines namely macrophage inflammatory protein alpha (MIP1alpha), MIP1beta and RANTES, in relation to disease status in HIV-1 infected individuals and compared with uninfected individuals. METHODS: RANTES and MIP1alpha were estimated using ELISA in 114 HIV-1 infected and 30 controls, whereas MIP1beta was estimated in 101 HIV infected individuals only and 30 controls. The values were compared to the T cell subsets, HIV-1 viral loads and plasma cytokines (interferon gamma and interleukin-10). RESULTS: Compared to controls the mean MIP1alpha and RANTES level among the HIV-1 infected individuals was higher while MIP1beta level was lower in HIV infected individuals except CDC C groups. There was a significant positive correlation for MIP1á with HIV-1 viral load and IFNgamma, for MIP1alpha with viral load and IL10. There was a significant negative correlation between MIP1alpha with CD4 count and CD4: CD8 ratio and MIP1beta with CD4 count and CD8 count. There was a negativecorrelation between RANTES values and CD8 per cent. INTERPRETATION & CONCLUSION: In conclusion, our study showed a significantly higher level of beta chemokines in south Indian HIV-1 infected individuals compared to controls. These beta chemokines may have the inhibitory effect on HIV-1 only during the initial period and with the progression of disease this inhibitory effect wanes as shown by the positive correlation of beta chemokines with HIV-1 viral load.

Hepatitis C virus genotype 6 infection in India.

We report two patients with chronic liver disease--a 46-year-old man and a 52-year-old woman, both from eastern India--who were found to be infected with hepatitis C virus genotype 6 strains. These strains have been previously reported only from Hong Kong and Southeast Asia.

Is dengue emerging as a major public health problem?

BACKGROUND & OBJECTIVES: Diagnosis of dengue infection is easily and best accomplished by demonstration of specific IgM antibodies in blood. We analyzed retrospectively the dengue IgM seropositivity available for samples obtained over a period of five year (1999-2003) from patients with suspected dengue fever (DF)-like illness to investigate whether there was an overall increase in the dengue IgM prevalence over this period. METHODS: Serum samples from a total of 1426 individuals (suspected dengue cases) obtained over five year were tested for dengue specific IgM antibodies. Of the 1426 patients, 693 were adults (>15 yr) and 694 children (<15 yr) (excluding 39 individuals whose age was not known). There were 807 males and 610 females (excluding 9 individuals whose status on sex was unknown). RESULTS: A total of 423 (29.7%) samples were positive for dengue IgM over the five year period. Overall, there was a significant increase in the percentage of dengue IgM positive individuals over the this period (P<0.001). When the individuals were grouped into children (<15 yr) and adults (>15 yr), a significant increase in the number of dengue IgM positive individuals was noticed only in children (P<0.001) and not in adults. When the individuals were grouped into males and females, a significant increase in the number of dengue IgM positive individuals was noticed in both the sexes (P<0.03). Month-wise analysis of the dengue IgM positivity rates indicated the year-wide occurrence of dengue. A total of 158 (41%) of the dengue IgM positive individuals showed positivity for dengue IgG also suggestive of a secondary heterotypic infection. INTERPRETATION & CONCLUSION: The overall significant increase in dengue IgM seropositivity among the suspected cases indicates an increase in dengue virus activity, raising the question whether dengue is emerging/re-emerging as a major health problem in southern India. Increase in probable secondary infection (as evidenced by dual positivity for dengue IgM and IgG) seen in this study is also a point of concern. Such an increase especially in a country like ours where multiple serotypes are prevalent, raises concern over probable increase in the incidences of the more serious DHF/DSS. As this report could well be an underestimate of true incidence, the alarming increase observed in 2003, may be a warning/indication of epidemics to come soon that merits serious consideration.

An outbreak of echovirus meningitis in children.

An outbreak of aseptic meningitis in children as evidenced by increase in the number of admissions in a tertiary care hospital is described. Clinical data and stool samples were collected from 25 hospitalized infants and young children. The stool samples were subjected to virological investigations. Fever and vomiting were the commonest symptoms. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis in majority of cases. Of the 25 stool samples, 14 showed an enterovirus specific cytopathogenic effect (CPE) in rhabdomyosarcoma (RD) cell line. All the 14 samples were positive for enterovirus RNA by reverse transcription-polymerase chain reaction (RT-PCR). Partial sequencing of the Virion protein 1 (VPI) region of the enterovirus genome carried out on the first 7 isolates revealed 5 isolates to be echovirus serotype 4 and one each to be echovirus serotypes 3 and 30. All children showed a rapid recovery and were discharged within 3 days of admission.

Hepatitis C virus genotypes: special reference to the Indian scene.

The heterogeneity observed between different isolates of the hepatitis C virus has led to stratification of these isolates into different genotypes. Clinically the genetic diversity of the virus has important implications as genotypes respond variably to antiviral therapy and can influence disease prognosis. This article attempts to summarize current knowledge about the different biological properties of HCV genotypes, and their geographical distribution, with special reference to the Indian scenario.

Increased number of CCR5+ CD4 T cells among south Indian adults probably associated with the low frequency of X4 phenotype of HIV-1 in India.

BACKGROUND & OBJECTIVE: The shift of the human immunodeficiency virus (HIV) from nonsyncytium inducing strains (NSI/R5) to syncytium inducing strains (SI/X4) seen in subtype B infections during progression to acquired immunodeficiency syndrome (AIDS) is less frequently reported in subtype C. NSI and SI strains differ in the co-receptor they utilize to infect a T-cell. We postulated that a larger pool of CD4 T cells expressing CCR5 would be present among individuals in the Indian population. To validate this hypothesis, we estimated the percentage of CD4 cells expressing CCR5 or CXCR4 molecules among healthy south Indian adults and HIV infected individuals. METHODS: HIV-1 infected and uninfected adult volunteers, belonging to the four southern states of India with Tamil/Malayalam/Kannada or Telugu as their spoken language were prospectively recruited. A two colour flowcytometry examination of the blood sample was done using the following monoclonals; anti-CD45 (FITC)/CD14 (PE), anti IgG1 (FITC)/IgG2a (PE), anti-CD3 (FITC)/CD4 (PE), anti-CD3 (FITC)/CD8 (PE), anti-CD4 (FITC) and anti CCR5 (PE) or anti CXCR4 (PE). RESULTS: In the healthy population (n = 30) studied, 24.6 per cent of CD4 T cells expressed CCR5 and the percentage of CD4 T cells expressing CXCR4 was 80.4. Among the HIV infected individuals (n = 51) the percentage of CD4 T cells expressing CCR5 and CXCR4 was 26.8 and 78.7 per cent respectively. INTERPRETATION & CONCLUSION: The percentage of CD4 cells expressing CCR5 and CXCR4 in both the HIV uninfected and infected adults was significantly higher in the south Indian population than in the West. The larger pool of CCR5 positive CD4 cells probably allows for the R5 HIV strain to have a replication advantage over X4 HIV strains. This may explain the lack of shift in the viral phenotype during disease progression and also the perceived rapid progression of the disease in India compared to the West.

A pilot study on the seroprevalence of parvovirus B19 infection.

BACKGROUND & OBJECTIVES: Human parvovirus B 19 (PVB 19) causes aplastic crisis in children with congenital haemolytic anaemia, erythema infectiosum, abortion and stillbirth. Since data on PVB 19 prevalence is lacking in India, a pilot study was undertaken to estimate the prevalence of IgG antibody in children and adults. METHODS: The samples were obtained from children attending our hospital and from volunteer blood donors, majority of whom were from south India. They included 45 children aged 1-5 yr, 39 aged 6-10 yr, 42 aged 11-15 yr and 100 healthy blood donors > 15 yr of age. Sera were tested for the presence of antibody to PVB 19 using a commercial enzyme immuno assay (EIA). RESULTS: Of 226 samples tested, 113 (50%) were positive for PVB 19 IgG. The prevalence of antibody increased from 8.9 per cent at 1-5 yr to 70 per cent in those > 15 yr: the median age of infection was between 6 and 15 yr. Sex and domiciliary status did not have significant effect on the prevalence of antibody. The IgG antibody index increased significantly with age, suggesting repeated exposure to the virus. INTERPRETATION & CONCLUSION: This seroprevalence study indicates that large numbers of individuals show exposure to PVB 19 virus. The exposure as indicated by IgG positivity is seen to increase with age. The IgG negative individuals may be considered to be at risk of developing infections due to PVB 19.