A study of TB-associated immune reconstitution inflammatory syndrome using the consensus case-definition.

BACKGROUND & OBJECTIVES: A considerable proportion of patients with HIV associated tuberculosis (TB) started on highly active antiretroviral therapy (HAART) develop immune reconstitution inflammatory syndrome (IRIS), which is difficult to diagnose in a resource-limited setting. In view of the recently proposed consensus case-definitions for TB-IRIS for use in resource-limited settings we undertook this study to describe the incidence and risk factors of TB associated IRIS in a tertiary care hospital and research centre in north India. METHODS: Retrospective analysis of antiretroviral treatment (ART) naïve adults started on highly active ART (HAART) from June 2006 to September 2008 was done. RESULTS: Of the 627 patients studied, 237 (38%) had TB at the initiation of HAART. In total, 18 (7.5%) of 237 patients with TB at baseline had paradoxical TB-associated IRIS, and 12 (3%) of 390 patients without TB at baseline developed ART-associated TB. Most IRIS events occurred during the initial 30 days of HAART. Two patients developed TB-associated IRIS after 90 days of HAART. Using univariate analysis, low CD4+ cell count at baseline [64 (28-89) vs. 95 (52-150); P=0.009] and early initiation of HAART [33 (24-41) vs. 48 (35-61) days; P<0.001] were significantly associated with paradoxical TB-associated IRIS. No identifiable risk factors were associated with the development of ART-associated TB. INTERPRETATION & CONCLUSION: A considerable proportion of patients on HAART develop TB-associated IRIS. The consensus case-definition is a useful tool in resource-limited settings for the diagnosis of TB- associated IRIS.

Outcomes of antiretroviral therapy in a northern Indian urban clinic.

PROBLEM: Antiretroviral therapy (ART) programmes have been successful in several countries. However, whether they would succeed as part of a national programme in a resource-constrained setting such as India is not clear. The outcomes and specific problems encountered in such a setting have not been adequately studied. APPROACH: We assessed the efficacy and functioning of India's national ART programme in a tertiary care centre in northern India. All ART-naive patients started on ART between May 2005 and October 2006 were included in the study and were followed until 31 April 2008. Periodic clinical and laboratory evaluations were carried out in accordance with national guidelines. Changes in CD4+ lymphocyte count, body weight and body mass index were assessed at follow-up, and the operational problems analysed. LOCAL SETTING: The setting was a tertiary care centre in northern India with a mixed population of patients, mostly of low socioeconomic status. The centre is reasonably well resourced but faces constraints in health-care delivery, such as lack of adequate human resources and a high patient load. RELEVANT CHANGES: The response to ART in the cohort studied was comparable to that reported from other countries. However, the programme had a high attrition rate, possibly due to patient-related factors and operational constraints. LESSONS LEARNT: A high rate of attrition can affect the overall efficacy and functioning of an ART programme. Addressing the issues causing attrition might improve patient outcomes in India and in other resource-constrained countries.

Pattern of Candida species isolated from patients with diabetes mellitus and vulvovaginal candidiasis and their response to single dose oral fluconazole therapy.

OBJECTIVE: Patients with diabetes mellitus are at increased risk of vulvovaginal candidiasis (VVC). Besides Candida albicans, they often have infection due to non-C. albicans Candida species such as C. glabrata. Oral single dose fluconazole (150 mg) is commonly used to treat VVC in non-diabetic individuals with response rate varying from 70 to 90%. However, there is paucity of related information in diabetic women with VVC. Present study has been conducted to systematically assess the effect of fluconazole therapy among diabetic patients with clinically symptomatic VVC. METHODS: Study subjects included 85 consecutive patients with diabetes mellitus (type 2=70 and type 1=15) and 62 non-diabetic women who had clinical signs and symptoms of VVC and in whom evidence of candidiasis was documented by presence of yeast on direct microscopy followed by culture. Single dose fluconazole (150 mg) was given orally to all the subjects in a supervised manner. Subjects were reassessed on 14th day after fluconazole therapy and a repeat high vaginal swab was taken for direct microscopy and fungal culture. Total glycosylated haemoglobin (HbA1) was measured to assess glycaemic control. RESULTS: There were no significant differences in the frequency of pruritus (55.9 vs. 56.7%), vaginal discharge (63.8 vs. 69.0%), dyspareunia (25.0 vs. 20.0%), and percentage yeast positivity (67.5 vs. 54.7%) between diabetic and control groups before the start of fluconazole therapy. Following fluconazole therapy, vaginal discharge on examination and yeast positivity on direct microscopy continued to remain positive in higher percentage of subjects in the diabetic group as compared to non-diabetic subjects (52.5 vs. 36.4%; P =0.22 and 50.7 and 29.0%, respectively, P =0.07, respectively). Overall 67.1% of patients with diabetes and 47.3% of controls continued to show persistence of Candida growth on high vaginal swab culture following fluconazole treatment (P=0.042). Candida glabtara was the most common species isolated in patients with diabetes mellitus and its frequency was significantly higher in them when compared to control group (54.1 vs. 22.6%, P<0.001). C. albicans was the most common species isolated in controls. Species-specific response to fluconazole showed that 81.3% of patients in the diabetic group and 78.6% of the non-diabetic controls continued to show fungal growth when C. glabrata was the organism grown (P=0.99). However, in case of C. albicans, 45.4% of the patients in the diabetic group and only 21.5% of the controls had persistent Candida growth following fluconazole therapy (P=0.22). CONCLUSION: Overall only one third of patients with diabetes mellitus and VVC respond to single dose 150 mg of fluconozole therapy. Limited response in the clinical symptoms and culture negativity following single dose fluconazole therapy in diabetic subjects with VVC is explained by the high prevalence of C. glabrata in them. The present study involved only 85 patients and majority of them had type-2 diabetes mellitus. There is need to perform similar study in large number of diabetics subjects including patients with type-1 diabetes mellitus and assess various alternative treatment protocol which are also effective in C. glabrata infection.

Glycaemic control and microvascular complication among patients with youth onset diabetes in India using differing types of insulin and methods of glucose monitoring.

We assessed whether insulin types and monitoring methods were relevant to glycaemic control, microvascular complications as well as costs of management in 208 patients with youth onset diabetes in India. The type of insulin and monitoring method used made no difference to the glycaemic and complication status. Cost considerations support bovine insulin use along with urine glucose monitoring as an appropriate approach to diabetes self care in developing countries.