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Background: Dengue is a significant mosquito-borne disease. Several studies have utilized estimates from the Global Burden of Disease (GBD) study to assess the global, regional or national burden of dengue over time. However, our recent investigation suggests that GBD's estimates for dengue cases in Taiwan are unrealistically high. The current study extends the scope to compare reported dengue cases with GBD estimates across 30 high-burden countries and territories, aiming to assess the accuracy and interpretability of the GBD's dengue estimates., Methods: Data for this study were sourced from the GBD 2019 study and various national and international databases documenting reported dengue cases. The analysis targeted the top 30 countries and territories with the highest 10-year average of reported cases from 2010 to 2019. Discrepancies were quantified by computing absolute differences and ratios between the 10-year average of reported cases and GBD estimates. Coefficients of variation (CV) and estimated annual percentage changes (EAPCs) were calculated to assess variations and trends in the two data sources., Results: Significant discrepancies were noted between reported data and GBD estimates in the number of dengue cases, incidence rates, and EAPCs. GBD estimates were substantially higher than reported cases for many entities, with the most notable differences found in China (570.0-fold), India (303.0-fold), Bangladesh (115.4-fold), Taiwan (85.5-fold) and Indonesia (23.2-fold). Furthermore, the GBD's estimates did not accurately reflect the extensive yearly fluctuations in dengue outbreaks, particularly in non-endemic regions such as Taiwan, China and Argentina, as evidenced by high CVs., Conclusions: This study reveals substantial discrepancies between GBD estimates and reported dengue cases, underscoring the imperative for comprehensive analysis in areas with pronounced disparities. The failure of GBD estimates to represent the considerable annual fluctuations in dengue outbreaks highlights the critical need for improvement in disease burden estimation methodologies for dengue., (© International Society of Travel Medicine 2024. Published by Oxford University Press.)

Background: Adverse events in fetuses are well researched but studies on the follow-up health outcomes of infants exposed to maternal motor vehicle crashes (MVCs) during pregnancy have yielded inconsistent results. This study aimed to investigate the association of maternal exposure to MVCs during pregnancy with the risk of adverse neonatal outcomes., Methods: This population-based cohort study used data from birth notifications in Taiwan. A total of 19 277 offspring with maternal exposure to MVCs during pregnancy and 76 015 randomly selected comparison offspring without such exposure were selected. Neonatal adverse outcomes were identified from National Health Insurance medical claims data. Conditional logistic regression was used to estimate the unadjusted and adjusted odds ratios (aORs) of neonatal adverse outcomes., Results: Offspring exposed to maternal MVCs during pregnancy had a higher risk of birth defects (aOR, 1.21; 95% CI, 1.04-1.41) than offspring without such exposure. This positive association was sustained with exposure to an MVC during the first or second trimester. A dose-response relationship (P = 0.0023) was observed between the level of injury severity and the risk of birth defects., Conclusions: In the early stages of pregnancy, maternal exposure to MVCs may entail a risk of birth defects in the offspring. The potential mechanisms for the associations of maternal exposure to MVCs with birth defects need further investigation., (© The Author(s) 2023; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Streptococcus pneumoniae infections have become increasingly complicated and costly to treat with the spread of antibiotic resistance. We evaluated the relationship between antibiotic prescribing and nonsusceptibility among invasive pneumococcal disease (IPD) isolates., Methods: Outpatient antibiotic prescription data for penicillins, cephalosporins, macrolides, and trimethoprim-sulfamethoxazole were abstracted from the IMS Health Xponent database to calculate the annual number of prescriptions per capita. We analyzed IPD data from 7 of the Centers for Disease Control and Prevention's Active Bacterial Core surveillance sites (population, 18.6 million) for which data were available for the entire time period under study (1996-2003). Logistic regression models were used to assess whether sites with high antibiotic prescribing rates had a high proportion of nonsusceptible and serotype 19A IPD., Results: Yearly prescribing rates during the period 1996-2003 for children <5 years of age decreased by 37%, from 4.23 to 2.68 prescriptions per capita per year (P < .001), and those for persons ≥5 years of age decreased by 42%, from 0.98 to 0.57 prescriptions per capita per year (P < .001); increases in azithromycin prescribing were noted for both groups. Sites with high rates of antibiotic prescribing had a higher proportion of IPD nonsusceptibility than did low-prescribing sites (P = .003 for penicillin, P < .001 for every other antibiotic class). Cephalosporin and macrolide prescribing were associated with penicillin and multidrug nonsusceptibility and serotype 19A IPD (P < .001)., Conclusions: In sites where antibiotic prescribing is high, the proportion of nonsusceptible IPD is also high, suggesting that local prescribing practices contribute to local resistance patterns. Cephalosporins and macrolides seem to be selecting for penicillin- and multidrug-resistant pneumococci, as well as serotype 19A IPD. Antibiotic use is a major factor contributing to the spread of antibiotic resistance; strategies to reduce antibiotic resistance should continue to include judicious use of antibiotics.

Background: Most deaths in the 1918 influenza pandemic were caused by secondary bacterial pneumonia., Methods: We performed a systematic review and reanalysis of studies of bacterial vaccine efficacy (VE) in preventing pneumonia and mortality among patients with influenza during the 1918 pandemic., Results: A meta-analysis of 6 civilian studies of mixed killed bacterial vaccines containing pneumococci identified significant heterogeneity among studies and estimated VE at 34% (95% confidence interval [CI], 19%-47%) in preventing pneumonia and 42% (95% CI, 18%-59%) in reducing case fatality rates among patients with influenza, using random-effects models. Using fixed-effect models, the pooled VE from 3 military studies was 59% (95% CI, 43%-70%) for pneumonia and 70% (95% CI, 50%-82%) for case fatality. Military studies showed less heterogeneity and may provide more accurate results than civilian studies, given the potential biases in the included studies. Findings of 1 military study using hemolytic streptococci also suggested that there was significant protection., Conclusions: Despite significant methodological problems, the systematic biases in these studies do not exclude the possibilities that whole-cell inactivated pneumococcal vaccines may confer cross-protection to multiple pneumococcal serotypes and that bacterial vaccines may play a role in preventing influenza-associated pneumonia.

The pharmacokinetic and pharmacodynamic modelling of insulin has been reported using a combined pharmacokinetic/pharmacodynamic (PK/PD) model, in which a hypothetical effect compartment is linked to a pharmacokinetic compartment. Review of the literature, however, indicated that the recently developed PK/PD models have consisted of an indirect pharmacodynamic response component, but none of them has been applied to the modelling of insulin. To study the relative relevance of the indirect pharmacodynamic response model and the effect-compartment link model in modelling the pharmacokinetics and pharmacodynamics of insulin, regular human insulin was administered intravenously at a dose of 0.1 IU kg(-1) to healthy Yucatan minipigs (after an overnight fasting). The plasma concentrations of insulin were measured by radioimmunoassay at predetermined time intervals, while blood glucose levels were monitored continuously using a glucose monitor. Analysis of the plasma insulin and the blood glucose profiles was performed by fitting with various PK/PD models and the results indicated that all of the 12 sets of plasma insulin data (after normalizing by the basal levels) have been adequately fitted to the two-compartment open pharmacokinetic model (a mean+/-s.e. correlation coefficient of 0.996+/-0.001 was obtained). The mean+/-s.e. correlation coefficient, the weighted residuals sum of squares (WRSS), and the Akaike's information criterion (AIC) were found, respectively, to be 0.935+/-0.008, 624+/-67, and 522+/-9 for the inhibitory indirect pharmacodynamic response model and 0.941+/-0.010, 547+/-63 and 513+/-9 for the stimulatory indirect pharmacodynamic response model, as compared with 0.725+/-0.041, 2309+/-276 and 628+/-10 for the effect-compartment link model. Based on these results, one may conclude that the indirect pharmacodynamic response model is a more appropriate approach for modelling the PK/PD of insulin than the effect-compartment link model.

Insulin lispro is a monomeric analogue of human insulin, produced by genetic engineering, and has been reported to have a more rapid absorption following subcutaneous injection than insulin. Since it has been shown to have a similar hypoglycaemic action to insulin in clinical studies and comparable properties in radioimmunoassay, the feasibility of using a bioassay which was designed originally for insulin, to measure insulin lispro potency was evaluated in this investigation. A random-dose bioassay protocol, in which insulin lispro and two insulin standards were administered intravenously in a random sequence, was used and validated in nine conscious healthy rabbits. The decline in blood-glucose levels, following the intravenous injection of a dose of insulin or its lispro analogue, was monitored by a continuous glucose monitoring system. A glucose response curve was generated, from which various pharmacodynamic parameters were determined. Compared with the insulin standards, the potencies of insulin lispro determined from nadir, basal glucose normalized nadir, glycaemic reduction and ABGC (area of the blood-glucose response curve under baseline) were observed to have mean (95% confidence limits) values of 97.0 (69.5-124.6)%, 106.3 (72.4-140.2)%, 949 (51.8-138.0)% and 102.4 (76.3-128.5)%, respectively. In addition, the coefficients of variation for correspondent parameters were 36.9, 41.5, 59.1 and 33.2%, respectively. The results indicated that the hypoglycaemic potency calculated from the ABGC values was the most accurate (102.4%) with the least coefficient of variation (33.2%). In conclusion, the potency of insulin lispro can be determined accurately from the ABGC values measured by the random-dose bioassay used.

A model antigen, bovine serum albumin (BSA), was successfully incorporated into microcapsules fabricated from blends of poly(d,l-lactide-co-glycolide) and poly(d,l-lactide). The microcapsules possessed diameters ranging from 10 to 100 microns and exhibited a continuous monophasic release of the protein in-vitro for 3 weeks. They were found to enhance its immunogenicity, thereby potentiating the anti-BSA antibody response following a single subcutaneous injection in mice and rabbits. Enzyme-linked immunosorbent assays demonstrated that the microcapsules provoked high-titre and long-lived immunoglobulin G immune responses over a period of 192 days in mice. When rabbits were immunized by a single subcutaneous injection of BSA-loaded microcapsules, a high level of anti-BSA antibody was still present in the sera obtained at 17 weeks post-injection. The immunization protocol using the BSA-loaded microcapsules was superior to that using BSA dissolved in saline or adsorbed to alum. These microcapsules providing the controlled release of antigens may be valuable in designing better vaccine formulations.