Risk Factors associated with defaulting from visceral leishmaniasis treatment: analysis under routine programme conditions in Bihar, India.

OBJECTIVE: To assess the rate of default from treatment in the visceral leishmaniasis (VL) elimination programme and to identify risk factors and its underlying causes. METHODS: Case-control study conducted between December 2009 and June 2012 in three primary health centres (PHCs) of Muzaffarpur district, India. Patients who defaulted from treatment from the PHCs were considered as 'cases' and those who completed their treatment as 'controls'. Two controls were included in the study for each case. Respondents' opinion and satisfaction with the services provided at the PHCs were also elicited. Logistic regression was performed to assess the contribution of sociodemographic variables on patient status, and a discriminant analysis was used (after decomposing the original data) to identify factors that can predict the patient status as defaulter or not, based on factor scores of the components as predictor variables. RESULTS: During the study period, 16.3% (89/544) of patients defaulted; 87 cases and 188 controls were interviewed through a semistructured questionnaire. Women tended to be more at risk for default (OR, 1.6, 95% CI (0.9 -2.9). Treatment received was miltefosine in 55.6% and sodium stibogluconate (SSG) in 44.4%. Most (86%) defaulters completed their treatment at other healthcare facilities; 70% of them preferred non-governmental institutions. Most cited reasons for default were seeking a second opinion for VL treatment and preferring to be treated in specialised VL centres. Discriminant analysis showed only one significant predictor: dissatisfaction with the medical care received in PHCs. CONCLUSION: Efforts are needed to enhance the quality of VL care at PHC level, which will be beneficial in increasing treatment completion rates.

Clinical profile and response to first-line ARV in HIV patients from Eastern UP and Bihar: a retrospective study.

BACKGROUND AND OBJECTIVES: Spectrum of infections in Human Immunodeficiency Virus (HIV) infected patient from Eastern UP and Bihar has not been systemically evaluated. This study was conducted with the following objectives; a) explore the spectrum of clinical conditions associated with HIV disease, b)the difference between clinical and investigatory parameters in those patients who presented with infection from those who present without infection and c) to evaluate the effect of anti-retroviral (ARV) therapy. METHODS: 1248 subjects who fulfilled the inclusion criteria were enrolled for the study from May 2007 to November 2008. Patients were evaluated for their baseline characteristics along with CD4 count and followed up for at least for 6 months after initiation of ARV (6-24 months). RESULT AND INTERPRETATION: In this retrospective study, tuberculosis (58.96%) was the commonest infection followed by chronic diarrhoea (26.56%) and various skin infections. Males had significantly higher incidence (p value < .001) of infection as compared to females. There was a significant difference between the patients who presented with infection from those who presented without infection for their baseline weight (42.3 vs 45.42), haemoglobin (9.06 vs 9.91), mean CD4 count at baseline (107.38 vs 128.38/microL) and CD4 count after 6 month of therapy (298.09 vs 322.98/microL). Mortality was also significantly high (p value < 0.05) in those who presented with infection (19.95% vs 15.1%), although there was no difference between these two groups on their improvement in CD4 count from baseline after 6 months of therapy. CONCLUSION: Among the spectrum of infection in HIV patient from North East part of India, tuberculosis was commonest, followed by skin infections and chronic diarrhoea. Patients who presented with infection at the time of initial presentation had a low haemoglobin, body weight and CD4 count and had high initial mortality but if they survived they show similar response to ARV therapy as patients who presented without infection.

Endocrine changes in male HIV patients.

AIMS AND OBJECTIVES: To determine the frequency of adrenal, thyroid and gonadal dysfunction in HIV positive male patients and to evaluate the endocrine function at different level of CD4 cell counts. MATERIAL AND METHODS: A total of 150 male HIV positive subjects were included in study. The patients were divided in three groups on the basis of CD4 cell counts. "Group A": HIV positive with CD4 count<200/mm "Group B": HIV positive with CD4 count 200-350/mm3 and "Group C": HIV positive with CD4 count>350/mm3. RESULTS: In "group A" (n=50) 2 patients had basal cortisol<5 microg/dl while 23 patients had basal cortisol>25 microg/ dl. 15 patients had subclinical hypothyroidism while 11 patients had overt hypothyroidism. 25 patients in this group had gonadal dysfunction: majority of them (24) had primary gonadal dysfunction (elevated LH). None of the patients in "group B" (n=50) had hypocortisolism while 11 patients had elevated cortisol; 18 had subclinical hypothyroidism while 4 had overt hypothyroidism while 17 patients were hypogonad, all having elevated LH. In "group C" (n=50) 2 patients had hypocortisolism and 5 had elevated cortisol; 12 patients had subclinical and one had overt hypothyroidism; 7 patients had primary hypogonadism and one had secondary hypogonadism. Overall 4(2.66%) had hypocortisolism while 39 (26%) had elevated cortisol; 45 (30%) had subclinical hypothyroidism while 16(10.66%) had overt hypothyroidism. Gonadal dysfunction was observed in 50 patients (33%) majority of them (48) had primary hypogonadism. On analysis of Pearson's correlation coefficient CD4 count has strong inverse correlation with basal cortisol (r=-0.301, p<0.0001), TSH (r=-0.257, p=0.002) and LH (r=-0.228, p=0.006), while there was a direct correlation with serum testosterone (r=0.175, p=0.037). CONCLUSION: This pilot study has demonstrated a high incidence of endocrine dysfunction in HIV infected patient in this part of country. High incidence of thyroid and gonadal dysfunction may contribute to morbidity of the patients and have a bearing on quality of life of the HIV infected patients. Hypocortisolism was not that common but high level of cortisol may be a marker of stress due to HIV per se or due to associated infection. Many of these dysfunctions might be transient and a large longitudinal study should be undertaken to substantiate the finding of the present study.

New treatment approach in Indian visceral leishmaniasis: single-dose liposomal amphotericin B followed by short-course oral miltefosine.

BACKGROUND: In Bihar, India, home to nearly one-half of the world's burden of visceral leishmaniasis, drug resistance has ended the usefulness of pentavalent antimony, which is the traditional first-line treatment. Although monotherapy with other agents is available, the use of 2 drugs with different modes of action might increase efficacy, shorten treatment duration, enhance compliance, and/or reduce the risk of parasite resistance. To test the feasibility of a new approach to combination therapy in visceral leishmaniasis (also known a kala-azar), we treated Indian patients with a single infusion of liposomal amphotericin B (L-AmB), followed 1 day later by short-course oral miltefosine. METHODS: We used a randomized, noncomparative, group-sequential, triangular design and assigned 181 subjects to treatment with 5 mg/kg of L-AmB alone (group A; 45 subjects), 5 mg/kg of L-AmB followed by miltefosine for 10 days (group B; 46 subjects) or 14 days (group C; 45 subjects), or 3.75 mg/kg of L-AmB followed by miltefosine for 14 days (group D; 45 subjects). When it became apparent that all regimens were effective, 45 additional, nonrandomized patients were assigned to receive 5 mg/kg of L-AmB followed by miltefosine for 7 days (group E). RESULTS: Each regimen was satisfactorily tolerated, and all 226 subjects showed initial apparent cure responses. Nine months after treatment, final cure rates were similar: group A, 91% (95% confidence interval [CI], 78%-97%]; group B, 98% (95% CI, 87%-100%); group C, 96% (95% CI, 84%-99%]; group D, 96% (95% CI, 84%-99%); and group E, 98% (95% CI, 87%-100%). CONCLUSIONS: These results suggest that treatment with single-dose L-AmB followed by 7-14 days of miltefosine is active against Indian kala-azar. This short-course, sequential regimen warrants additional testing in India and in those regions of endemicity where visceral leishmaniasis may be more difficult to treat. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00370825 .

Safety of a pre-formulated amphotericin B lipid emulsion for the treatment of Indian Kala-azar.

Amphotericin B (AB) deoxycholate is highly effective in antimony refractory cases for the treatment of visceral leishmaniasis (VL) in Bihar. But the need for prolonged hospitalisation and frequent, occasionally serious, adverse events are its major drawbacks. Lipid formulations of AB are devoid of these problems, but very expensive. We evaluated the safety and efficacy of a commercial standardised amphotericin B emulsion, a product of AB formulated in lipid emulsion vehicle (ABLE) in the treatment of Indian VL. In this open label, non-comparative study, 15 patients in each group were given three daily intravenous infusions each of 3, 4 or 5 mg/kg. All 45 patients (15 in each group) completed the treatment. The drug was tolerated well. Infusion reactions occurred in 5 (11%) patients and vomiting in 2 (4.4%). No nephrotoxicity or other organ toxicity was observed. At the end of treatment all patients of every group were clinically and parasitologically cured. However, during 6 months follow up, three patients from the 5 mg/kg group and one from the 4 mg/kg group tested positive for splenic aspirate. Thus 41 (91.1%; 95% CI 78-97) of 45 patients were cured with a total dose ranging between 9 and 15 mg/kg. There was no dose response linear correlation. In this preliminary study, AB formulated in a lipid emulsion vehicle was safe and effective for the treatment of VL in India.

Correlation between clinical features and degree of immunosuppression in HIV infected children.

We conducted this study to find out correlation of CD4% with clinical status in 102 HIV infected antiretroviral naive children. Mean age of presentation was 4.8 years. Perinatal transmission was the commonest mode of transmission (94%). Fever (53%), chronic diarrhea (36%), and cough (29%) were the commonest presenting symptoms. Protein energy malnutrition was seen in 56.7% of children. 33.3% children were asymptomatic, whereas 45.1% were in WHO clinical stages III and IV at the time of presentation. The most common opportunistic infection was tuberculosis. CD4% correlated significantly with the deterioration of the WHO clinical stages (P<0.01) and increasing grades of protein energy malnutrition (P< 0.05).

Amphotericin B treatment for Indian visceral leishmaniasis: response to 15 daily versus alternate-day infusions.

BACKGROUND: For patients with Indian visceral leishmaniasis, amphotericin B deoxycholate is usually given as 15 alternate-day infusions of 1 mg/kg over 30 days (total dose, 15 mg/kg); daily treatment with 1 mg/kg for 20 days (total dose, 20 mg/kg) is also used. This study was done to address the unsettled therapeutic questions of administration schedule (alternate-day vs. daily administration) and dose (1 vs. 0.75 mg/kg) and to determine whether the duration of amphotericin B treatment in Bihar, India, can be shortened to 15 days. METHODS: To compare alternate-day versus daily administration and 1-mg/kg versus 0.75-mg/kg doses and to determine whether the duration of treatment could be abbreviated, Indian subjects randomly received 15 infusions of 1 mg/kg (group A; 245 patients) or 0.75 mg/kg (group B; 244 patients) on alternate days or 1 mg/kg (group C; 500 patients) or 0.75 mg/kg (group D; 496 patients) daily. Noninferiority testing compared 6-month cure rates using a 5% margin. RESULTS: Overall, 1439 of the 1485 subjects completed treatment and responded. Treatment interruptions (nephrotoxicity) but not infusion-associated reactions or study removals were more common with daily administration. Final cure rates at 6 months were similar: group A, 234 patients (96%; 95% confidence interval [CI], 92%-98%); group B, 225 patients (92%; 95% CI, 88%-95%); group C, 483 patients (97%; 95% CI, 95%-98%); and group D, 476 patients (96%; 95% CI, 94%-97%; P>.05). CONCLUSIONS: Provided that the serum creatinine level is repeated once, daily treatment with amphotericin B, 0.75 mg/kg for 15 days (total dose, 11.25 mg/kg), is efficient and effective for visceral leishmaniasis in India. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00310505.

Study on clinico-epidemiological profile of HIV patients in eastern India.

In this study, 438 HIV positive patients attending the HIV clinic of Sir Sundar Lal Hospital, IMS, BHU were enrolled. Of these 354 were males (mean CD4 count 179 +/- 9.3 cells/microl) and 84 were females (mean CD4 count 323 +/- 28.26 cells/microl). The mean age of the study subjects at the time of diagnosis was 32.6 years. Heterosexual contact was the commonest mode of transmission in 352 (80.4%) patients followed by blood transfusion in 2.5%. History suggestive of a risk factor for HIV transmission could not be elicited in 62 (14.1%) patients. Among male patients, 71.5% were migrant workers. Fever (70.6%), weight loss (53.3%), chronic diarrhea (43.9%) and cough (40.3%) were the common presenting symptoms. Out of the 438 patients, 66.4% had opportunistic infections at the time of reporting to the hospital. The most common opportunistic infection was tuberculosis (38.8%) followed by oropharyngeal candidiasis (20.3%) and diarrhea (12.7%). CD4 counts of the patients were significantly inversely correlated with the number of symptoms and the number of opportunistic infections (correlation coefficient were -.289 and -.236 respectively).

Identification, antifungal resistance profile, in vitro biofilm formation and ultrastructural characteristics of Candida species isolated from diabetic foot patients in Northern India.

PURPOSE: Diabetic foot ulcers are a serious cause of diagnostic and therapeutic concern. The following study was undertaken to determine the fungal causes of diabetic foot ulcers, with their phenotypic and genotypic characterisation. MATERIALS AND METHODS: A total of 155 diabetic foot ulcers were studied for 1 year. Deep tissue specimen was collected from the wounds, and crushed samples were plated on Sabouraud dextrose agar with chloramphenicol (0.05 g). Identification was done by growth on cornmeal agar, germ tube formation and urease test. For molecular identification, conserved portion of the 18S rDNA region, the adjacent internal transcribed spacer 1 (ITS1) and a portion of the 28S rDNA region were amplified, using the ITS1 and ITS2 primers. Antifungal susceptibility against voriconazole, fluconazole and amphotericin B was determined by standard broth microdilution method. Biofilm formation was studied in three steps. First, on the surface of wells of microtiter plates followed by quantification of growth by fungal metabolism measurement. Finally, biofilms were analysed by scanning electron microscopy (SEM). RESULTS: Fungal aetiology was found in 75 patients (48.38%). All were identified as Candida species (100%). The prevalence of different species was Candida tropicalis (34.6%), Candida albicans (29.3%), Candida krusei (16.0%), Candida parapsilosis (10.6%), Candida glabrata (9.33%). All were susceptible to amphotericin B (100%). On microtiter plate, all the isolates were viable within 48 h showing biofilms. The metabolic activity of cells in the biofilm increased with cellular mass, especially in the first 24 h. On SEM, majority showed budding yeast form. CONCLUSION: Non-albicans Candida spp. with potential biofilm forming ability are emerging as a predominant cause of diabetic foot ulcers.

Evaluation of rK28 antigen for serodiagnosis of visceral Leishmaniasis in India.

Antibody detection is a safely applied method at the wide scale in diagnosis of visceral Leishmaniasis (VL). In order to further advance serodiagnosis, the rK28 antigen has been recently introduced as a candidate for diagnosis of VL. We evaluated the sensitivity and specificity of the rK28 antigen in a micro-ELISA format in comparison to the rk39 antigen. The test was conducted on 252 parasitologically confirmed VL cases, 103 endemic healthy controls, 95 non-endemic healthy controls, 88 other infectious disease and 53 follow-up cases. Of 252 parasitologically confirmed VL cases, 251 cases were reported positive by rK28 antigen, yielding 99.6% sensitivity (95% CI, 0.97-0.99), which was similar to the sensitivity of rK39 ELISA (99.6%) (95% CI, 0.97-0.99). Specificity of the rK28 antigen in non-endemic and endemic healthy controls was 100% (95% CI 0.96-1) and 94.17% (95% CI, 0.88-0.97), respectively. In 88 different diseases, specificity was 95.45% (95% CI, 0.84-0.96). With the rK39 antigen, specificity of non-endemic and endemic controls and different diseases was 100% (95% CI 0.96-1), 92.23% (95% CI 0.85-0.96) and 96.59% (95% CI 0.90-0.98), respectively. Our results show that rK39 and rK28 antigens have similar sensitivity and specificity and rK28 can also be used as a serodiagnostic tool in the endemic population of Bihar.

Safety and efficacy of high-dose infusions of a preformed amphotericin B fat emulsion for treatment of Indian visceral leishmaniasis.

Amphotericin B deoxycholate is used as a first-line drug for visceral leishmaniasis (VL) in India. Its major drawbacks are prolonged hospitalization of treated patients and toxicity. An open label phase II study with pre-formed amphotericin B lipid emulsion (ABLE) was conducted to evaluate safety and efficacy of four regimens of 15 mg/kg each administered in 1-2 doses. Regimen 1 was 7.5 mg/kg/day on day 1 and day 3, and regimen 4 was a single bolus infusion of 15 mg/kg. The safety profile was excellent with mild infusion reactions seen in 38% of the patients. Definitive cure was achieved in 100% of the patients treated with regimen 4. The overall cure rate was 87% (95% confidence interval = 75-94%). In this study, ABLE was safe and had excellent efficacy when given as a bolus of 15 mg/kg. More studies with larger number of patients and higher doses are needed to establish acceptable, safe and efficacious regimen.

Ratio of LDH isozymes H4 and H3M as diagnostic index in suspected cases of myocardial infarction.

The isozyme profile of lactic dehydrogenase (LDH) is being studied in this laboratory, mainly for the diagnosis in the suspected cases of myocardial infarction (MI). The isozymes are separated by polyacrylamide gel electrophoresis and the quantitative assay of the isoenzymes is done by enzyme staining followed by scanning with the help of an automatic scanner. In normal cases, the ratio of the two isozymes H4 and H3M is approximately 0.5. In almost all cases of myocardial infarction the ratio becomes 1 or more and sometimes increases up to 2. In the suspected and potential cases of infarction the ratio tends to become more than 0.5 (usually 0.7) but remains lower than 1. Thus, the measurement of the ratio may be a very helpful diagnostic index in the suspected and potential cases and may also be used for prognostic purposes as well.