HIV-associated lymphoma: A 5-year clinicopathologic study from India

Context: Relative risk of non-Hodgkin lymphoma (NHL) in people living with HIV is 60–200 times that of normal population. This is the largest series from India on lymphomas arising in HIV-infected individuals including workup for Epstein–Barr virus (EBV) and human herpesvirus-8 (HHV-8). Aims: This study aims to ascertain the distribution and detailed clinicopathologic features of lymphoma arising in HIV-infected persons in India. Settings and Design: The study was done during the period of 2007–2011 in the pathology department of a tertiary care center in South India. Subjects and Methods: All cases diagnosed as lymphoma in the department of pathology during the study period were identified, and patients with HIV positive by serology were included in the study. Clinical details were obtained from electronic records, slides were reviewed and tissue blocks retrieved, and immunohistochemistry for HHV-8 and in situ hybridization for EBV-encoded RNA was done. Statistical Analysis Used: Descriptive statistics were done using SPSS software. Kaplan–Meier curves were used to do survival analysis. Results: Of 3346 patients diagnosed with lymphoma, 73 (2%) were diagnosed to be positive for HIV. About 87.6% of the cases were NHL, of which diffuse large B-cell lymphoma was the most common and plasmablastic lymphoma was the second common subtype. Survival was uniformly poor in 36% of the cases where follow-up was available. Conclusions: The striking differences from world literature included higher frequency of plasmablastic lymphomas, lack of primary central nervous system lymphomas, and low association with HHV8.

BK virus characterisation among HIV-1-Infected individuals and its association with immunosuppression

Purpose: BK virus (BKV) is an opportunistic pathogen which causes significant morbidity and mortality in individuals who are immunodeficient. We aimed to quantitate and characterise BKV and to correlate with the degree of immunosuppression among human immunodeficiency virus (HIV)-1-infected individuals. Methods: BKV DNA detection was carried out using an in-house quantitative real-time polymerase chain reaction on paired whole-blood and urine samples collected from 187 antiretroviral therapy (ART)-naïve HIV-1-infected individuals and 93 healthy individuals who served as controls. Sequencing was performed for a proportion of high BK viral load (VL) samples to observe non-coding control region (NCCR) rearrangements. Results: BKV positivity in urine was 25.6% among HIV-infected individuals and 10.7% in control individuals (P = 0.03). The BK VL showed a significant negative correlation with CD4+ T-cell counts, a positive correlation with WHO clinical staging and no significant correlation with HIV-1 VL. Of 42 BKVs from urine samples sequenced, two showed rearrangements without clinically severe disease or high VL. Their NCCR and VP1 sequence-based genotyping revealed genotype I. In a small subset of individuals (n = 8) on ART who were being followed up, six individuals showed either decrease or complete clearance of virus with ART. Conclusion: There was a higher frequency of BK viruria in HIV-1-infected individuals than among healthy controls and the positivity correlated with the degree of immunosuppression. There was no association of high VL with NCCR rearrangements in urine.

Disseminated histoplasmosis.

OBJECTIVE: To study the clinical features and natural history of disseminated histoplasmosis(DH) in India. METHODS: We retrospectively analyzed the data obtained from the in-patient medical records of adults (age > 13 years) diagnosed to have DH during the period from January 1989 to December 1999. DH was diagnosed when histologically compatible intracellular organisms were present or Histoplasma capsulatum was obtained in culture from the extrapulmonary sites. RESULTS: Nineteen patients (18 male and 1 female) were diagnosed to have DH. Diabetes mellitus and HIV infection were the most common co-morbid conditions. Weight loss, fever and oropharyngeal ulcers were the commonest symptoms. Physical signs included hepatosplenomegaly, oropharyngeal ulcers and lymphadenopathy. The diagnosis was confirmed by histopathology and/or culture from the following sites: bone marrow, adrenal gland, lymph node, oropharyngeal ulcers, rectal mucosa and skin. Two patients were treated with Amphotericin B, 6 with various azoles and 3 had Amphotericin B followed by various azoles. Among the eleven treated, 7 were cured, 2 improved, 1 had a relapse and 1 patient died. CONCLUSION: DH is not uncommon in India and should be considered in the diagnosis of patients with prolonged fever, weight loss, oropharyngeal ulcers, hepatosplenomegaly, lymphadenopathy and adrenal enlargement. Correct diagnosis and treatment leads to a favourable outcome.

Oxidative damage in intermediate syndrome of acute organophosphorous poisoning.

BACKGROUND & OBJECTIVES: The main cause of morbidity due to organophosphate poisoning is intermediate syndrome (Type II paralysis) that can occur 48-72 h after poisoning. Mechanisms that underlie the intermediate syndrome are not known. This study investigates the role of oxidative damage to muscles as a possible mechanism underlying the development of the intermediate syndrome. METHODS: Nineteen patients with acute organophosphate poisoning were evaluated from admission to discharge from intensive care for the severity of poisoning and the development and duration of the intermediate syndrome. Blood cholinesterases and parameters of oxidative stress were studied daily and their temporal profiles analysed according to the severity of poisoning and the development and duration of the intermediate syndrome. RESULTS: Fifteen patients had severe poisoning and 16 developed intermediate syndrome. There was a positive association between the severity of poisoning and the occurrence of intermediate syndrome. There was no association between the organophosphate ingested and the development of intermediate syndrome. Erythrocyte membrane acetylcholinesterase and serum butyrylcholinesterase levels at admission and over the course of poisoning were significantly (P < 0.001) reduced in patients compared to controls. There were significantly (P < 0.05) higher levels of lipid peroxidation, conjugated dienes and protein thiols in erythrocyte membranes of patients who developed the intermediate syndrome compared to healthy controls, in patients who developed intermediate syndrome compared to those who did not and in patients with long compared to short duration intermediate syndrome. INTERPRETATION & CONCLUSION: In acute organophosphate poisoning, severe and prolonged acetylcholinesterase inhibition is associated with oxidative stress, detected in erythrocyte membranes, that occurs early in the course of poisoning and may contribute to the development and severity of intermediate syndrome.

CD4 counts of normal and HIV-infected south Indian adults: do we need a new staging system?

BACKGROUND: The normal range of CD4 lymphocyte count varies among different ethnic groups. In populations with CD4 counts inherently lower than in the West, the Centers for Disease Control and Prevention (CDC) classification system of HIV-infected individuals may not be appropriate. No such criterion is currently available for ethnic south Indian HIV-infected individuals. We undertook this study to assess the applicability of the western case definition to south Indian HIV patients. METHODS: The CD4 counts of 104 normal and 79 HIV-infected south Indian adults were estimated by flowcytometry. The mean CD4 counts were estimated and compared between CDC groups A, B and C and controls. Receiver operator characteristics curves were generated to determine the cut-off that correlated best with clinical staging for this population. RESULTS: The mean CD4 and CD8 cell counts/microl and the CD4/CD8 ratio of the control group were 799.0, 919.6 and 0.94, respectively. For CDC groups A, B and C, the mean CD4 counts/microl were 454.4, 254.4 and 168; mean CD8 counts/microl were 1156, 1070.9 and 1191.3; and mean CD4/CD8 ratios were 0.44, 0.25 and 0.15, respectively. CONCLUSION: The mean CD4 count among normal south Indians is significantly lower than that in the western population and parallels that of the Chinese. When categorized based on the CDC classification system, the mean CD4 count of HIV-infected individuals was lower. Categories of CD4 counts > 300, 81-300 and < or =80 cells/microl and CD4% > 14, 7-14 and < or = 6 correlate better with disease progression among HIV-infected individuals. A longitudinal study is required before guidelines for the Indian population can be devised.

Enteric pathogens in southern Indian HIV-infected patients with & without diarrhoea.

This study was undertaken to determine the carriage rate of various enteric pathogens in southern Indian patients with HIV infection, both with and without diarrhoea. Stool from 111 consecutive HIV-positive patients (50 without and 61 with diarrhoea) was examined by microscopy and culture. Jejunal biopsy and fluid examination were carried out if diarrhoea persisted, with negative stool examination. Enteric pathogens were detected from stool in 57.4 per cent of diarrhoeal patients compared to 40 per cent of those without diarrhoea (P > 0.05). Jejunal biopsy and fluid examination provided 11 additional diagnoses. Protozoa accounted for 71.8 per cent of all pathogens isolated. Isospora was significantly more common in patients with (11/61) than in those without (2/50) diarrhoea (P < 0.05). Bacterial pathogens were isolated more commonly from patients with diarrhoea (12/61 compared to 2/50, P < 0.05). Isolation rate of pathogens was higher from patients with diarrhoea for more than 2 wk, compared to those with less than 2 wk duration. Remission of diarrhoea either spontaneously or with symptomatic therapy was observed in 22 patients with acute diarrhoea. A high enteric carriage of a number of pathogens was noted in HIV patients without diarrhoea, but I. belli and bacterial enteropathogens were more likely to be associated with diarrhoea.

Epidemiological features of acquired immunodeficiency syndrome in southern India.

AIDS was diagnosed in 187 men and 24 women (M:F = 8:1) from April 1987 till December 1994 at the Christian Medical College Hospital, Vellore. The doubling time of the occurrence of AIDS cases was 14 months; during 1987-90 there were an average of 5.7 cases per year; in 1991-93 there were 28 per year; in 1994 there were 104 cases. The mean age of patients was 33 yr for men and 31 for women. Among men, the primary mode of infection was heterosexual contact with female commercial sex workers. Among women, the most common source of infection was their husbands. There were 4 bisexuals and one homosexual subject who might have acquired infection by having sex with other men. There were 135 subjects from urban and 76 from rural communities. Most subjects belonged to the lower socio-economic classes. These data show that HIV infection had been very widespread in this region, both urban and rural.

Epithelioid granulomas in Hodgkin's disease--prognostic significance.

Prognostic significance of non-caseating epithelioid granulomas in association with Hodgkin's disease has been studied. Such granulomas were found in 15 of the total of 104 cases of Hodgkin's disease encountered between Jan. 1981 and June 1990. These 15 patients were compared with 30 concurrent patients of Hodgkin's disease who did not have associated granulomas. All the patients were initially staged, treated and followed up for a period of two years. There was no significant difference in overall survival rate between the granuloma group and the control group. However, in relapse free survival rate in advanced stages of the disease (III & IV), although the difference between granuloma group and the control group was not statistically significant (p = 0.11), yet the relapse free survival curves revealed a tendency towards better survival with lesser number of relapses and longer remissions in granuloma group.

Rational drug use--evaluation of a training programme for interns.

A workshop covering various aspects of rational drug use was conducted for interns of Christian Medical College, Ludhiana. Evaluation of the workshop revealed that it was able to bring about an attitudinal change regarding rational drug use. The methodology and evaluation procedures have been described. It is suggested that similar attempts should be made at all medical colleges so that every graduate enters medical practice with a positive attitude towards rational drug use.

Bone marrow involvement in Hodgkin's disease -- clinicopathological study of seven cases.

Bone marrow involvement was observed in 7 cases amongst a total of 75 cases of Hodgkin's disease encountered between January 1981 and June 1990; thus representing an incidence of 9.3 percent. Analysis of these 7 cases showed male preponderance. The age ranged from 26 to 74 years. All patients presented within seven months of onset of symptoms; and all had symptoms at presentation. Lymphadenopathy was found in all the cases, splenomegaly was present in six; and hepatomegaly in 4 cases. Mixed cellularity and lymphocytic depletion subtypes showed the highest frequency of marrow involvement (6 cases; 85.7 percent). Alkaline phosphatase was raised in 6 cases (85.7%). All cases received standard combination chemotherapy with or without local radiation therapy. Two years follow-up revealed an overall survival of 42.9%. Replace free survival at the end of two years was zero, as all the cases relapsed within seven months of initiation of treatment.

Hodgkin's disease: a clinicopathologic study.

One hundred and four cases of Hodgkin's disease diagnosed between July 1981 and June 1991 have been analysed. There was a definite male preponderance. Majority of the patients (82.7%) were below the age of 50 years. Mixed cellularity was the most common type (57.7%). It was followed by both nodular sclerosis and lymphocyte predominant types (16.3% each). Lymphocyte depletion Hodgkin's disease, the most aggressive variant, was the least common (9.7%). The detailed observations, as compared to the previous studies in this region as well as in other parts of the world have been presented and discussed.