Under-recognition and reporting of dengue in Cambodia: a capture-recapture analysis of the National Dengue Surveillance System.

Robust disease burden estimates are important for decision-making concerning introduction of new vaccines. Dengue is a major public health problem in the tropics but robust disease burden estimates are lacking. We conducted a two-sample, capture-recapture study in the largest province in Cambodia to determine disease under-recognition to the National Dengue Surveillance System (NDSS). During 2006-2008, community-based active surveillance for acute febrile illness was conducted in 0- to 19-year-olds in rural and urban areas combined with testing for dengue virus infection. Of 14 354 individuals under active surveillance (22 498 person-seasons), the annual incidence ranged from 13·4 to 57·8/1000 person-seasons. During the same period, NDSS incidence rates ranged from 1·1/1000 to 5·7/1000, which was 3·9- to 29·0-fold lower than found in the capture-recapture study. In hospitalized cases, the rate of under-recognition was 1·1- to 2·4-fold. This study shows the substantial degree of under-recognition/reporting of dengue and that reported hospitalized cases are not a good surrogate for estimating dengue disease burden.

Changes in calculated arterio-jugular venous glutamate difference and SjvO2 in patients with severe traumatic brain injury.

BACKGROUND: Cerebral metabolic impairment is feared to induce secondary brain damage following traumatic brain injury (TBI). The present study was designed to assess the temporal profile of calculated arterio- jugular venous differences in glutamate (AJVDglu) and SjvO(2) in patients subjected to continuous pharmacologic coma. Metabolic impairment was assumed to be reflected by increased jugular venous glutamate levels and decreased jugular venous oxygen saturation (SjvO(2)). METHODS: Arterial and jugular venous blood was drawn once daily for up to 14 days from 14 patients to assess the temporal profile. Plasma glutamate was measured by high performance liquid chromatography. SjvO(2), lactate and paCO(2) were determined in routine blood gas analysis. Calculated AJVD indirectly reflects cerebral uptake (positive values) or cerebral release (negative values). RESULTS: During pharmacologic coma an increase in ICP approaching 20 mmHg was associated with significantly reduced paCO(2) (4.7 ± 0.5 kPa; mean ± standard deviation), markedly decreased SjvO(2) (66.0 ± 4.2%) without reaching ischemic values, and a trend to more negative AJVDglu values (-6.0 ± 14.3 µmol/L), suggesting cerebral glutamate release. Arterio- jugular venous lactate difference (AJVDlac) remained unchanged. CONCLUSION: During pharmacologic coma increased ICP was associated with significantly decreased SjvO(2) which coincided only with a trend to increased cerebral glutamate release. Calculated AJVDglu appears to be inferior in unmasking altered brain metabolism compared to SjvO(2) whenever ICP is increased.

Interactions of glycyrrhizin with organic anion transporting polypeptides of rat and human liver.

Glycyrrhizin (GL) is used in Japan for the treatment of chronic hepatitis C. Following intravenous administration, GL is eliminated mainly by excretion into bile. Hepatocyte uptake of GL is a carrier-mediated process with characteristics resembling the organic anion transporting polypeptides (OATPs, solute carrier gene family SLC21A). We, therefore, studied whether GL is a potential transport substrate of the OATPs of rat and human liver. Because transport of GL could not be measured directly, GL-mediated cis-inhibition of [3H]estrone-3-sulfate or [35S]bromosulfophthalein uptake was analyzed kinetically in Xenopus laevis oocytes injected with cRNA coding for OATPs. GL inhibited [3H]estrone-3-sulfate uptake by 75-100% in oocytes expressing rat Oatp4, human OATP-C or human OATP8, members of the OATP1B subfamily that are expressed predominantly in hepatocytes. Dixon plots indicated a non-competitive type of inhibition, with Ki values of 6.1, 15.9 and 12.5 µmol/l, respectively. In contrast, GL inhibition of rat Oatp1, Oatp2 and Oatp3 and human OATP-A and OATP-B was only between 0 and 53%. In conclusion, GL is an inhibitor and, therefore, potentially a transport substrate of the liver-specific OATPs in rat and man. The rate at which GL is taken up into the liver may depend upon the function and expression levels of these hepatocellular OATPs.