Intravenous cyclophosphamide for lupus nephritis in Thai children

OBJECTIVE: To evaluate the efficacy of a 36-month course of intravenous cyclophosphamide therapy for severe lupus nephritis in Thai children between October 1993 and December 2000. METHODS: Intravenous cyclophosphamide combined with oral prednisolone was given for 36 months to patients with systemic lupus erythematosus (SLE) who had severe renal involvement. Serum creatinine (Cr), creatinine clearance (CCr), urinary protein, C3, and complete blood count (CBC) were measured each visit for intravenous cyclophosphamide. Repeated measures ANOVA and Kaplan-Meier survival analysis were used. RESULTS: Of 21 patients enrolled in the study, three died and two were lost to follow-up, leaving 16 patients who completed therapy (13 females and three males) with age at diagnosis 12.1+/-2.3 years (range 7.2-20.6 years). The follow-up period was 6.3+/-2.3 years (range 3.3-13.8 years). Fourteen patients had lupus nephritis WHO classification class IV and two had lupus nephritis WHO classification class II. Hypertension was detected in ten patients. Lowess smoothing curves and repeated measures ANOVA indicated no significant change in Cr and CCr [probability (p) > 0.05)], but significantly increased C3 and haemoglobin and significantly decreased urinary protein and white blood cell count (p < 0.001). Five patients had six episodes of acute renal failure; one died, renal function returned to normal in two patients, two continued to chronic renal failure, and one died of chronic renal failure. The 5-year survival and renal survival were 86.5% and 87.5% (95% CI 55.8-96.5% and 58.6-96.7%), respectively. CONCLUSION: Intravenous cyclophosphamide in severe lupus nephritis in Thai children showed a satisfactory outcome with minimal complications. Further follow-up is needed.     

Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B

AIM： To investigate peripheral T-lymphocyte sub-population profile and its correlation with hepatitis B virus （HBV） replication in patients with chronic hepatitis B （CHB）.METHODS： Distribution of T-lymphocyte subpopulations in peripheral blood was measured by flow cytometry in 206 CHB patients. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time polymerase chain reaction （PCR）. The relationship between HBV replication and variation in peripheral T-cell subsets was analyzed.RESULTS： CHB patients had significantly decreased CD3^＋ and CD4^＋ cells and CD4^＋/CD8^＋ ratio, and increased CD8^＋ cells compared with uninfected controls （55.44 ± 12.39 vs 71.07 ± 4.76, 30.92 ± 7.48 vs 38.94 ± 3.39, 1.01 ± 0.49 vs 1.67 ± 0.33, and 34.39 ± 9.22 vs 24.02 ± 4.35; P 〈 0.001, respectively）. Univariate analysis showed a similar pattern of these parameters was significantly associated with high viral load, presence of serum hepatitis B e antigen （HBeAg） expression, liver disease severity, history of maternal HBV infection, and young age at HBV infection, all with P 〈 0.01. There was a significant linear relationship between viral load and these parameters of T-lymphocyte subpopulations （linear trend test P 〈 0.001）. There was a negative correlation between the levels of CD3＋ and CD4＋ cells and CD4^＋/CD8^＋ ratio and serum level of viral load in CHB patients （r = -0.68, -0.65 and -0.75, all P 〈 0.0001）, and a positive correlation between CD8^＋ cells and viral load （r = 0.70, P 〈 0.0001）. There was a significant decreasing trend in CD3^＋ and CD4^＋ cells and CD4^＋/CD8^＋ ratio with increasing severity of hepatocyte damage and decreasing age at HBV infection （linear trend test P 〈 0.01）. In multiple regression （after adjustment for age at HBV infection, maternal HBV infection status and hepatocyte damage severity） log copies of HBV DNA maintained a highly significant predictive coefficient on T-lymphoc     

A prospective evaluation of four immunodiagnotic assays for human leptospirosis

This was a prospective evaluation of four immunodiagnostic assays for human leptospirosis, including the indirect immunofluorescence test (IFA), the microscopic agglutination test (MAT), the LEPTO dipstick, and the latex agglutination (LA) test. Four hundred ninety-two serum samples were collected from 348 patients who presented with acute fever without localizing signs. The sensitivities of the IFA, MAT, Dipstick, and LA were 91.9, 76.6, 77.4, and 83.1%, respectively. The specificities of these assays were 100.0, 100.0, 89.3, and 83.5, respectively. Even though IFA showed the highest overall sensitivity and specificity, when acute sera were considered, the LA was the most sensitive (28.7%). All 3 genus specific antibody assays had broad reactivity against various serogroups. The MAT is best suited for the reference laboratory, where it can be maintained with the battery of live antigens; the IFA is suited for a laboratory with sophisticated equipment and technical expertise; the Dipstick and LA are suitable for peripheral laboratories which lack expensive equipment and expertise.     

Randomized clinical trial: efficacy and safety of telbivudine and lamivudine in treatment-naïve patients with HBV-related decompensated cirrhosis

Summary. Patients with decompensated cirrhosis owing to chronic hepatitis B viral (HBV) infection have a high morbidity/mortality rate, and the treatment remains a challenge. We studied the safety and efficacy of telbivudine and lamivudine in such patients. This noninferiority, double‐blind trial randomized 232 treatment‐naive patients with decompensated HBV (1:1) in 80 academic hospitals to receive once‐daily telbivudine 600 mg or lamivudine 100 mg for 104 weeks. Primary composite endpoint was proportion of patients with HBV DNA <10 000 copies/mL, normal alanine aminotransferase (ALT) and Child‐Turcotte‐Pugh score improvement/stabilization at week 52. Response rates using a post hoc modified endpoint (HBV DNA <300 copies/mL [57 IU/mL] and ALT normalization) in intent‐to‐treat analysis (missing = failure) were 56.3%vs 38.0% after 76 weeks (P = 0.018) and 45.6%vs 32.9% after 104 weeks (P = 0.093) for telbivudine vs lamivudine. Telbivudine treatment was an independent predictive factor for HBV DNA <300 copies/mL and ALT normalization (P = 0.037). Response rates with protocol‐defined composite endpoint in intent‐to‐treat analysis (M = F) were 56.2 vs 54.0% (noninferiority not achieved) and 39.1%vs 36.4% (noninferiority achieved) in telbivudine and lamivudine groups at 52 and 104 weeks. Telbivudine treatment was associated with a significant improvement in glomerular filtration rate compared to lamivudine treatment and was also associated with a trend for improvement in survival (87%vs 79%). No cases of lactic acidosis were reported. Telbivudine compared to lamivudine was associated with a higher rate of patients with both viral suppression and ALT normalization, a trend towards a higher rate of survival and significant improvement in glomerular filtration.     

Randomized trial of albinterferon alfa-2b every 4 weeks for chronic hepatitis C virus genotype 2/3

Summary. Albinterferon alfa‐2b (albIFN) is a fusion protein of recombinant human albumin/recombinant interferon (IFN)‐α‐2b, with ～200‐h half‐life. Safety/efficacy of albIFN q4wk was evaluated in 391 treatment‐naive patients with chronic hepatitis C virus (HCV) genotype 2/3. Patients were randomized 3:4:4:4 to one of four open‐label treatment groups: pegylated IFN (Peg‐IFN)‐α‐2a 180 μg qwk or albIFN 900, 1200 or 1500 μg q4wk, plus oral ribavirin 800 mg/day, for 24 weeks. Primary efficacy endpoint was sustained virologic response (SVR; HCV RNA <20 IU/mL 24 weeks post‐treatment). SVR rates were as follows: 85%, 76%, 76% and 78% with Peg‐IFNα‐2a and albIFN 900, 1200 and 1500 μg, respectively (P = NS); corresponding rapid virologic response rates (HCV RNA <43 IU/mL at week 4) were as follows: 78%, 49% (P < 0.001), 60% (P = 0.01) and 71%. SVR rates were not influenced by interleukin 28B genotype, although rapid virologic response rates were greater with interleukin 28B CC (P = NS). Serious adverse event rates were as follows: 4%, 11%, 3% and 3% with Peg‐IFNα‐2a and albIFN 900, 1200 and 1500 μg, respectively. No increase in serious/severe respiratory events was noted with albIFN. Fewer absolute neutrophil count reductions <750/mm³ occurred with albIFN (P = 0.03), leading to fewer IFN dose reductions. Haemoglobin reductions <10 g/dL were less frequent with albIFN 900 and 1200 μg vs 1500 μg and Peg‐IFNα‐2a (P = 0.02), leading to fewer ribavirin dose reductions. albIFN administered q4wk produced fewer haematologic reductions than Peg‐IFNα‐2a, but had numerically lower SVR rates (P = NS) in patients with chronic HCV genotype 2/3.     

Production and purification of Burkholderia pseudomallei BipD protein

Type III secretion system (TTSS) clusters contain virulent genes of both animal and plant Gram-negative bacteria. The full length (933 bp) gene of bipD, a member of TTSS cluster of Burkholderia pseudomallei, was isolated by PCR amplification from B. pseudomallei DNA and cloned into pGEX 4T-1. GST-BipD fusion protein and BipD protein obtained by removal of GST using thrombin were employed to detect the presence of B. pseudomallei antibodies in sera obtained from melioidosis and non-melioidosis patients by immunoblotting. Sensitivity and specificity of BipD protein was 100% and 91.1%, respectively, whereas that of fusion protein was 77.8% and 90.0%, respectively.     

Measuring stigma associated with tuberculosis and HIV/AIDS in southern Thailand: exploratory and confirmatory factor analyses of two new scales

Objective  To develop scales to measure tuberculosis and HIV/AIDS stigma in a developing world context.
Methods  Cross-sectional study of tuberculosis patients in southern Thailand, who were asked to rate their agreement with items measuring TB and HIV/AIDS stigma. Developing the scales involved exploratory and confirmatory factor analyses, internal consistency, construct validity, test–retest reliability and standardized summary scores.
Results  Factor analyses identified two sub-scales associated with both tuberculosis and HIV/AIDS stigma: community and patient perspectives. Goodness-of-fit was good (TLI = 94, LFI = 0.88 and RMSEA = 0.11), internal consistency was excellent (Cronbach's alphas 0.82–0.91), test–retest reliability was moderate, and construct validity showed an inverse correlation with social support.
Conclusion  Our scales have good psychometric properties that measure stigma associated with tuberculosis and HIV/AIDS and allow assessment of stigma from community and patient perspectives. Their use will help document the burden of stigma, guide the development of interventions and evaluate stigma reduction programmes in areas with a high HIV/AIDS and tuberculosis burden.