Dog Bites in Humans and Estimating Human Rabies Mortality in Rabies Endemic Areas of Bhutan

Dog bites in humans are a public health problem worldwide. We conducted a hospital based questionnaire survey and described the incidence and risk factors for human dog bites in Bhutan. We also estimated the human death rate attributable to rabies in two rabies endemic areas of south Bhutan. Our study shows that dog bites incidents in humans are common in the survey areas. There were significant gender and age differences in bite incidents; males and the children are affected the most. The majority of the victims were bitten by stray dogs, increasing the risk of rabies infection if not treated in time. Our decision tree model predicted 2.23 (95% CI: 1.20–3.59) human deaths from rabies/year, equivalent to an annual incidence of 4.67 (95% CI: 2.53–7.53) deaths/100,000 in the two rabies endemic areas of south Bhutan. In the absence of post exposure prophylaxis, the model predicted 19.24 (95% CI: 13.69–25.14) deaths/year in these two areas. The public should be encouraged to visit hospitals for post exposure prophylaxis following dog bite injury in south Bhutan

Neurocognition and quality of life after reinitiating antiretroviral therapy in children randomized to planned treatment interruption

Objective: Understanding the effects of antiretroviral treatment (ART) interruption on neurocognition and quality of life (QoL) are important for managing unplanned interruptions and planned interruptions in HIV cure research. Design: Children previously randomized to continuous (continuous ART, n=41) vs. planned treatment interruption (PTI, n=47) in the Pediatric European Network for Treatment of AIDS (PENTA) 11 study were enrolled. At study end, PTI children resumed ART. At 1 and 2 years following study end, children were assessed by the coding, symbol search and digit span subtests of Wechsler Intelligence Scale for Children (6-16 years old) or Wechsler Adult Intelligence Scale ( 6517 years old) and by Pediatrics QoL questionnaires for physical and psychological QoL. Transformed scaled scores for neurocognition and mean standardized scores for QoL were compared between arms by t-test and Mann-Whitney U test, respectively. Scores indicating clinical concern were compared (<7 for neurocognition and <70 for QoL tests). Results: Characteristics were similar between arms with a median age of 12.6 years, CD4 + of 830 cells/\u3bcl and HIV RNA of 1.7 log 10 copies/ml. The median cumulative ART exposure was 9.6 in continuous ART vs. 7.7 years in PTI (P=0.02). PTI children had a median of 12 months off ART and had resumed ART for 25.2 months at time of first assessment. Neurocognitive scores were similar between arms for all tests. Physical and psychological QoL scores were no different. About 40% had low neurocognitive and QoL scores indicating clinical concern. Conclusion: No differences in information processing speed, sustained attention, short-term memory and QoL functioning were observed between children previously randomized to continuous ART vs. PTI in the PENTA 11 trial

Pharmacokinetics and 24-week efficacy/safety of dual boosted saquinavir/lopinavir/ritonavir in nucleoside-pretreated children.

Contains fulltext : 49117.pdf (publisher's version ) (Closed access)OBJECTIVE: To assess the pharmacokinetics and 24-week efficacy and safety of dual boosted saquinavir/lopinavir/ritonavir combination in children. DESIGN: Twenty reverse transcription inhibitor-pretreated children at 2 centers in Thailand were treated with saquinavir/lopinavir/ritonavir in an open label, single arm, 6-month prospective study. The dosage was 50 mg/kg twice daily (bid) for saquinavir and 230/57.5 mg/m bid for lopinavir/ritonavir. Ten children also received lamivudine. METHODS: Samples were collected for a 12-hour pharmacokinetic profile in all children. Plasma concentrations of saquinavir, lopinavir and ritonavir were determined using a validated high performance liquid chromatography technique. RESULTS: At baseline, the median age was 8.5 years, with human immunodeficiency virus (HIV) RNA 4.9 log10 copies/mL, CD4 count 129 cells/microL and CD4%, 6.5%. Median area under the concentration curve at 0-12 hours and Cmin were 39.4 mg/L.h and 1.4 mg/L for saquinavir and 118 mg/L.hr and 5.9 mg/L for lopinavir. After 24 weeks of treatment, HIV RNA was suppressed below 400 copies/mL for 16 of 20 (80%) children (intent-to-treat analysis) and below 50 copies/mL for 12 of 20 children (60%), and CD4% (count) rose by a median of 6% (216 cells/microL). Median changes of triglyceride and total cholesterol were 56 and 36.5 mg/dL, respectively (P = 0.01). Lopinavir Cmin 400 copies/mL, and lopinavir Cmax >15 mg/L correlated with rises in cholesterol (P < 0.05). CONCLUSION: Plasma drug concentrations of saquinavir, lopinavir and ritonavir were at the higher limits of expected ranges for adult treatment at approved dosages (1000/100 mg bid for saquinavir, 400/100 mg bid for lopinavir/ritonavir). The regimen was well-tolerated and had good efficacy at 24 weeks. This dual boosted protease inhibitor combination should be assessed in larger trials of reverse transcription inhibitor-experienced children