Causes of first hospitalization among 1121 HIV-infected children: comparison of the pre-Pneumocystis jiroveci pneumonia prophylaxis, pre-antiretroviral therapy and antiretroviral therapy periods

This study identified causes of first hospitalization among perinatally acquired HIV-infected children at Chiang Mai University Hospital between 1989 and 2009. Data were stratified into three seven-year time periods: pre-Pneumocystis jiroveci pneumonia (PJP) prophylaxis, pre-antiretroviral therapy (ART) and ART period. Over the 21-year study period, 1121 children were hospitalized. The mean age at admission was 2.7 years and had become older over time. Of the 1121 hospitalization causes, 50.6% were AIDS-defining illnesses (ADIs), 48.1% were non-AIDS-defining illnesses (NADIs) and 1.3% were related to immune reconstitution syndrome. Types of ADIs changed over time: PJP and recurrent Salmonella septicaemia decreased, while mycobacterial infection and systemic fungal infection increased. For NADIs, bacterial infections, viral infections and gastrointestinal problems decreased, but haematological problems increased in the third period. Decline in the number of hospitalizations and mortality rate, increase in the mean age of hospitalized children, change in the distribution of specific illnesses and appearance of immune reconstitution syndrome were observed in the ART period.     

Reference values for thrombotic markers in children

Thromboembolic events are an increasingly common problem encountered in children. The laboratory diagnosis of thrombotic disorders in children differs from that in adults. To establish the normal reference of natural anticoagulant parameters in children of different age groups, plasma from healthy children between the ages of 2 months and 16 years (n = 127) and adults (n = 30) were assayed for a disintegrin-like and metalloprotease with thrombospondin type 1 domain 13 (ADAMTS-13), von Willebrand factor collagen-binding activity (vWF:CB), tissue factor pathway inhibitor (TFPI), homocyteine and natural anticoagulants. Children were divided into four age groups: less than 1 year, 1-5 years, 6-10 years, and 11-16 years. The reference values for ADAMTS 13, homocysteine, and protein C activity were significantly lower in children of all age groups compared with those in the adults. Similarly, those for protein C antigen, total protein S, free protein S and antithrombin III (AT III) for children less than 1 year were significantly lower than in the adults. On the contrary, TFPI levels were significantly higher in the children for all age groups when compared with the adults. vWF:CB levels were comparable across all groups. There are age-related physiologic differences in ADAMTS-13, TFPI, homocysteine and natural anticoagulants between children and adults. Our data will provide physicians with a useful reference guide in interpreting test results of inhibitors of hemostatic parameters in children suspected of thrombotic disorders.     

Epidemiology of bloodstream infections and predictive factors of mortality among HIV-infected adult patients in Thailand in the era of highly active antiretroviral therapy

Few studies have described the pattern of bloodstream infections (BSI) among HIV-infected patients in the highly active antiretroviral therapy (HAART) era, particularly in resource-limited settings. A retrospective cohort study was conducted among 140 HIV-infected patients who had a positive blood culture from 2004-2008. Of the 140 patients, 91 (65%) were male with a mean (SD) age of 38 (9.1) years and a median (IQR) CD4 cell count of 32 (9-112) cells/mm(3). Community-acquired infection was detected in 89% of patients. The blood cultures contained Gram-negative bacteria, 40%; fungi, 24%; Mycobacterium spp., 20%; and Gram-positive bacteria, 16%. Common causative pathogens were Cryptococcus neoformans, 21%; Salmonella spp., 15%; and Mycobacterium tuberculosis, 12%. Common focal sites of infection were the central nervous system, 24%; respiratory tract, 20%; and gastrointestinal tract, 18%. CD4 cell count (OR, 0.61 per 50 cells/mm(3) increment; 95% CI, 0.39-0.96; P = 0.031) was the only factor associated with mycobacterial or fungal BSI. The crude mortality was 21%. HAART (OR, 0.23; 95% CI, 0.01-0.77; P = 0.017), focal infection (OR, 0.31; 95% CI, 0.10-0.97; P = 0.044), and complication (e.g., shock) (OR, 9.26; 95% CI, 3.25-26.42; P < 0.001) were the predictive factors of mortality. In conclusion, opportunistic infections are still the leading causes of BSI among HIV-infected patients in the HAART era.     

A superior test for diagnosis of Clostridium difficile-associated diarrhea in resource-limited settings

In this prospective cohort study, we investigated the prevalence of Clostridium difficile-associated diarrhea (CDAD) in adult patients with nosocomial diarrhea by performing enzyme immunoassay (EIA) for detecting toxins A and B and polymerase chain reaction (PCR) for detecting the presence of the tcdB gene in stool samples. We determined the factors associated with CDAD, and the treatment outcome of CDAD from May 2010 to January 2011. A total of 175 stool samples were tested by EIA and PCR. In total, 26.9% patients tested positive for C. difficile: 12.6% by EIA and 24.0% by PCR. The kappa coefficient and total agreement of both the tests were 0.46 and 83.2%, respectively. Onset of diarrhea after antibiotic administration for 10 days or more (OR, 2.71; 95% CI, 1.14-6.44; P = 0.024) and leukocyte count >15,000 cells/mm(3) (OR, 3.12; 95% CI, 1.24-7.88; P = 0.016) were significantly associated with occurrence of CDAD. The non-response rate to CDAD treatment was 24.1%, and the all-cause mortality rate was 31.9% in the CDAD group as against 35.9% in the non-CDAD group (P = 0.721). In our study, the performance of direct PCR of stool samples for detecting tcdB was better, with the number of positive results for stool toxins A and B being twofold higher than that in the case of EIA. Patients who have diarrhea after receiving antibiotics for 10 days or more or those who have a leukocyte count of >15,000 cells/mm(3) should be investigated for CDAD.     

Response-guided therapy for patients with hepatitis C virus genotype 6 infection: a pilot study

Summary. The optimal duration of treatment with pegylated interferon (PEG‐IFN) plus ribavirin (RBV) in patients with hepatitis C virus (HCV) genotype 6 is unknown. This study was aimed at determining treatment response on the basis of rapid virological response (RVR) of HCV genotype 6 in comparison with genotypes 1 and 3. Sixty‐six treatment naïve patients were treated with PEG‐IFN‐α2a (180 μg/week) plus weight‐based RBV (1000–1200 mg/day). Patients with genotype 1 n = 16) and genotype 3 (n = 16) were treated for a fixed duration of 48 and 24 weeks, respectively. Patients with genotype 6 (n = 34) who achieved RVR were treated for 24 weeks (response‐guided therapy) and the remaining patients were treated for 48 weeks (standard therapy). The mean baseline HCV RNA levels were not statistically different between groups (6.4 ± 0.8, 6.0 ± 1.0 and 6.5 ± 0.8 Log₁₀ IU/mL for genotypes 1, 3 and 6, respectively). Patients with genotypes 1, 3 and 6 achieved RVR in 43.8%, 87.5% and 73.5% of cases, respectively. One patient with genotype 1 and 3 with genotype 6 were considered nonresponders and discontinued therapy. Sustained virological response (SVR) was achieved in 62.5%, 81.3% and 76.5% of patients with genotypes 1, 3 and 6, respectively. The SVR rate in patients with genotype 6 who underwent response‐guided therapy was 88%. This pilot study suggested that the SVR rate of HCV genotype 6 was at an intermediate level between those of genotypes 3 and 1. Treatment with PEG‐IFN plus RBV for 24 weeks may be sufficient for patients with genotype 6 who achieve RVR. Prospective randomized trials are required to evaluate this response‐guided strategy in a larger number of patients with genotype 6.