Comparison of 3 infrared thermal detection systems and self-report for mass fever screening

Despite limited evidence regarding their utility, infrared thermal detection systems (ITDS) are increasingly being used for mass fever detection. We compared temperature measurements for 3 ITDS (FLIR ThermoVision A20M [FLIR Systems Inc., Boston, MA, USA], OptoTherm Thermoscreen [OptoTherm Thermal Imaging Systems and Infrared Cameras Inc., Sewickley, PA, USA], and Wahl Fever Alert Imager HSI2000S [Wahl Instruments Inc., Asheville, NC, USA]) with oral temperatures (≥ 100 °F = confirmed fever) and self-reported fever. Of 2,873 patients enrolled, 476 (16.6%) reported a fever, and 64 (2.2%) had a confirmed fever. Self-reported fever had a sensitivity of 75.0%, specificity 84.7%, and positive predictive value 10.1%. At optimal cutoff values for detecting fever, temperature measurements by OptoTherm and FLIR had greater sensitivity (91.0% and 90.0%, respectively) and specificity (86.0% and 80.0%, respectively) than did self-reports. Correlations between ITDS and oral temperatures were similar for OptoTherm (ρ = 0.43) and FLIR (ρ = 0.42) but significantly lower for Wahl (ρ = 0.14; p < 0.001). When compared with oral temperatures, 2 systems (OptoTherm and FLIR) were reasonably accurate for detecting fever and predicted fever better than self-reports.     

Detection of mycobacterial antigen responses in lung but not blood in HIV-tuberculosis co-infected subjects

Forty-seven HIV-infected adults had broncho-alveolar lavage stimulated with purified protein derivate of Mycobacterium tuberculosis. Eighteen of 19 (95%) with tuberculosis co-infection had interferon-gamma synthetic CD4 lymphocyte responses > 1% versus three of 28 (11%) without (P < 0.0001). Lung response was unrelated to blood CD4 cell count. BAL HIV tuberculosis responses were similar in 25 HIV-uninfected tuberculosis patients. Responses in matched blood samples were often undetectable. Therefore, immunological tuberculosis assays seem less affected by HIV co-infection when lung-based.     

Treatment and Eradication of Murine Fur Mites: I. Toxicologic Evaluation of Ivermectin-Compounded Feed

Fur mite outbreaks remain a persistent problem in laboratory mouse colonies. All currently published treatment methods are labor-intensive, expensive, or unreliable. During a recent outbreak with Myobia musculi and Myocoptes musculinus in a large colony (approximately 30,000 cages), we developed a feed-based treatment regime in which ivermectin was the active ingredient. Rodent feed was compounded with 3 different concentrations of ivermectin (12, 24, and 48 ppm) and γ-irradiated. Postcompounding analysis revealed loss of ivermectin during manufacturing, but the remaining drug was stable for at least 6 mo. In an 8-wk toxicity study in a C57BL/6NTac mouse breeding colony, ad-libitum feeding of the 3 diets yielded estimated doses of 1.3, 2.7, and 5.4 mg/kg. Adult mice lacked adverse clinical effects, except that 1 of the 144 mice in the 48-ppm group developed tremors and ataxia and was euthanized. No significant differences between doses were revealed by CBC, serum chemistry, body weight, or gross necropsy. Plasma drug concentrations plateaued at a dose-dependent level 7 to 10 d after initiation of treatment and decreased to undetectable levels 6 to 9 d after its discontinuation. Fertility of the P0 generation was unaffected. Pup mortality was higher in the 24- and 48-ppm groups, reaching 100% at the higher dose. Animals exposed to ivermectin as neonates had normal weaning weights, but mice receiving 24-ppm feed had lower adult weights. Our results indicate that using feed containing 12 ppm ivermectin (estimated ingested dose, 1.3 mg/kg) was safe in a C57BL/6NTac breeding colony.Fur mites are a persistent problem in laboratory mouse colonies.^8,12 Fur mite infestations can affect animals’ health and compromise experimental results.¹⁶ Clinical signs in infested mice include localized pruritus, alopecia, ulcerative dermatitis, lymphadenopathy, and weight loss.^39,40 Immunocompetent mice mount a robust humoral response characterized by hypergammaglobulinemia, markedly elevated IgE levels, lymphocytopenia, eosinophilia, and alterations in inflammatory cytokines.^18,35 Therefore, effective treatment is imperative in the interest of both the animals and the research in which they are used.More than a dozen reports have been published in laboratory animal science journals over the last 25 y describing various fur mite treatments. ^{3,4,7,9,13,14,23,26,28,29,36,39,41} Despite the large number of regimens and acaricides described, fur mites remain a concern for laboratory mouse colonies. The last 2 comprehensive surveys, which were conducted almost 10 y apart (1996 and 2006) and assessed prevalence of adventitious agents in major United States research institutions, indicated that fur mites were present in 30% to 40% of the institutions responding.^8,17 Despite great advancements in laboratory animal science and technologies, the prevalence of rodent fur mite infestation in laboratory mouse colonies apparently has remained relatively stable, as compared with that of other adventitious infective agents.We recently experienced a fur mite outbreak with both Myobia musculi and Myocoptes musculinus in all 3 of our vivaria, affecting 30,000 cages (described elsewhere in this issue).³⁰ Briefly, the infestation was identified simultaneously in 3 distinct but interconnected vivaria. The fur mites most likely were introduced on imported animals, whose infestation evaded detection during quarantine. Subsequently, the infestation was spread inadvertently and rapidly by transferring large numbers of cages between vivaria. Ultimately, about 40% of the animal rooms became infested. Because of the fulminant nature of this outbreak, the entire rodent population in all 3 facilities required treatment. A treatment regimen that could be deployed facility-wide in an efficient and cost-effective manner was needed.Most protocols describing effective fur mite eradication require individual treatment of animals or cages or the preparation of medicated water bottles for each cage.^{3,4,7,9,14,36,39} These methods, when applied to very large colonies, are cumbersome, labor-intensive, expensive, and (most importantly) lack proven long-term efficacy. In our program, we routinely and successfully use rodent feed compounded with anthelminthics, antibiotics, and supplemental vitamins to treat mice.²⁵ In our hands, medicated feed has served as an efficient and effective way of delivering therapeutics to animals requiring treatment for days to weeks.Since the advent of avermectin class drugs in 1981, most fur mite treatment protocols have incorporated their use. These agents have been administered through various routes, doses, and schedules, as a monotherapy or in combination with other agents.^{3,7,14,23,28,36,41} Avermectins have powerful broad-spectrum antiparasitic activity against most endo- and ectoparasites and act by binding GABA-gated chloride and invertebrate-specific glutamate-gated anion channels in peripheral neuromuscular synapses, suppressing nerve impulse conduction.³⁷ Ivermectin was the first avermectin developed specifically for and introduced to the veterinary market.²¹ Since its introduction, ivermectin at doses as low as 0.2 mg/kg has proven effective in killing rodent fur mites in small, well-defined outbreaks and controlled experiments.^{4,9,14,23,32,41} Today, ivermectin is readily available in bulk quantities at very low cost. By delivering ivermectin in feed, we could avoid the difficult labor and expense associated with individual treatment of more than 120,000 mice or administering the drug weekly in more than 30,000 water bottles.Although ivermectin has a wide safety margin in most mammalian species, some animals are particularly sensitive to ivermectin toxicity. Neonatal mice, which have an immature blood brain barrier, and adult mice and dogs with defective P-glycoprotein are most at risk to ivermectin toxicity, even when given at doses as low as 0.4 mg/kg.^20,21,31 In addition, typical therapeutic doses have been shown to cause adverse effects in various mouse strains or stocks and dog breeds with normal levels of P-glycoprotein.^5,21 In addition, ivermectin has been shown to alter aspects of behavior and immune function in mice.^6,10,18Reported ivermectin doses for mice vary from 0.2 to 4 mg/kg and appear to have been chosen arbitrarily.^{3,9-11,14,19,23,24,28,33} Moreover, most dose recommendations are much higher than the no-effect-dose reported in the literature.²¹ Therefore, we sought to identify the highest-possible ivermectin concentration that could be provided to mice in feed for an extended period of time without causing adverse effects on neonates and adults or during pregnancy and lactation.     

Pathogenesis of pandemic H1N1 2009 influenza virus infection and the implication on management

The pandemic H1N1 2009 influenza virus has caused the first influenza pandemic of the 21st century, leading to disproportionate fatalities in the low-risk population despite the generally mild nature of the illness. Advances in sci     

Cost of opioid-related adverse drug events in surgical patients

Opioids have demonstrated efficacy and often are drugs of choice in the management of postoperative pain. However, their use is often limited by adverse drug events (ADEs). The objective of this study was to determine the ADE rate in adult surgical patients who received opioids and the impact of opioid ADEs on length of stay (LOS), costs, and mortality. A hospital-based computerized system detected potential ADEs. Adult patients were selected if they received at least one dose of opioid medication during a surgical hospitalization between 1 January 1990 and 31 December 1999. Control patients were matched based on matching length of stay ([LOS] at least as long as time to ADE), age (within 10 years), sex, admission year, major disease category (MDC), and without an ADE. Linear regression models were used to determine the predictors of increased LOS, total hospital costs, and log-transformed total hospital costs. 60,722 patients received opioid medication during their surgical hospitalization and 2.7% experienced an opioid-related ADE. The most common clinical manifestations were nausea and vomiting (67%), and rash, hives, or itching (33.5%). No statistically significant difference was seen in mortality between ADE/non-ADE patients. ADE patients had statistically significant increases in LOS (0.53 days) and in log-transformed cost (16%). The estimated log cost difference of 16%, if applied to the median cost patient in the non-ADE group, averaged US$ 840. Opioid-related ADEs are common in hospitalized patients and increase LOS and total hospital costs.