Quantitative Models of the Dose-Response and Time Course of Inhalational Anthrax in Humans

Anthrax poses a community health risk due to accidental or intentional aerosol release. Reliable quantitative dose-response analyses are required to estimate the magnitude and timeline of potential consequences and the effect of public health intervention strategies under specific scenarios. Analyses of available data from exposures and infections of humans and non-human primates are often contradictory. We review existing quantitative inhalational anthrax dose-response models in light of criteria we propose for a model to be useful and defensible. To satisfy these criteria, we extend an existing mechanistic competing-risks model to create a novel Exposure–Infection–Symptomatic illness–Death (EISD) model and use experimental non-human primate data and human epidemiological data to optimize parameter values. The best fit to these data leads to estimates of a dose leading to infection in 50% of susceptible humans (ID₅₀) of 11,000 spores (95% confidence interval 7,200–17,000), ID₁₀ of 1,700 (1,100–2,600), and ID₁ of 160 (100–250). These estimates suggest that use of a threshold to human infection of 600 spores (as suggested in the literature) underestimates the infectivity of low doses, while an existing estimate of a 1% infection rate for a single spore overestimates low dose infectivity. We estimate the median time from exposure to onset of symptoms (incubation period) among untreated cases to be 9.9 days (7.7–13.1) for exposure to ID₅₀, 11.8 days (9.5–15.0) for ID₁₀, and 12.1 days (9.9–15.3) for ID₁. Our model is the first to provide incubation period estimates that are independently consistent with data from the largest known human outbreak. This model refines previous estimates of the distribution of early onset cases after a release and provides support for the recommended 60-day course of prophylactic antibiotic treatment for individuals exposed to low doses.     

Interactive effects of senescence and natural disturbance on the annual survival probabilities of snail kites

Individuals in wild populations face risks associated with both intrinsic (i.e. aging) and external (i.e. environmental) sources of mortality. Condition‐dependent mortality occurs when there is an interaction between such factors; however, few studies have clearly demonstrated condition‐dependent mortality and some have even argued that condition‐dependent mortality does not occur in wild avian populations. Using large sample sizes (2084 individuals, 3746 re‐sights) of individual‐based longitudinal data collected over a 33 year period (1976–2008) on multiple cohorts, we used a capture–mark–recapture framework to model age‐dependent survival in the snail kite Rostrhamus sociabilis plumbeus population in Florida. Adding to the growing amount of evidence for actuarial senescence in wild populations, we found evidence of senescent declines in survival probabilities in adult kites. We also tested the hypothesis that older kites experienced condition‐dependent mortality during a range‐wide drought event (2000–2002). The results provide convincing evidence that the annual survival probability of senescent kites was disproportionately affected by the drought relative to the survival probability of prime‐aged adults. To our knowledge, this is the first evidence of condition‐dependent mortality to be demonstrated in a wild avian population, a finding which challenges recent conclusions drawn in the literature. Our study suggests that senescence and condition‐dependent mortality can affect the demography of wild avian populations. Accounting for these sources of variation may be particularly important to appropriately compute estimates of population growth rate, and probabilities of quasi‐extinctions.     

Effect of acute oral administration of captopril and MK-421 on vascular angiotensin converting enzyme activity in the spontaneously hypertensive rat

Vascular angiotensin converting enzyme (ACE) may be important as a potential site of action for the antihypertensive effect of ACE inhibitors. ACE activity, estimated by hydrolysis of [³H] HipGlyGly, was similar in the aorta, mesenteric and carotid arteries of SHR. ACE activity in veins was not as consistent and was significantly lower in the jugular veins and vena cava of SHR than in the arteries. Nevertheless, ACE activity in all the blood vessels examined, although less than lung ACE activity, was higher than ACE activity found in other tissues such as brain, heart and kidney. Equieffective antihypertensive doses of captopril (10 mg/kg p.o.) and MK-421 (1.0 mg/kg p.o.) dramatically inhibited ACE activity in all the arteries and veins examined. Maximal ACE inhibition occured within 15 minutes after the oral administration of captopril. In contrast, maximal ACE inhibition was slower in onset and of longer duration after MK-421 than after captopril for all the vessels. Thus, relatively high ACE activity can be measured in both arteries and veins from the spontaneously hypertensive rat (SHR) and ACE was dramatically inhibited after antihypertensive oral doses of captopril or MK-421. Furthermore, vascular ACE inhibition can be used to compare the onset and duration of activity of ACE inhibitors; MK-421 has a longer onset and duration in SHR than captopril based on inhibition of ACE in blood vessels.     

Effects of retinoic acid on chick tail bud development

The present study describes the teratogenic effects of retinoic acid (RA) on the development of the chick tail bud. Chick embryos were recovered 48 hours after treatment at HH stages 11 to 16 with various dosages of RA by subblastodermal injection. At the gross level, RA treatment resulted in varying degrees of caudal regression, scoliosis, limb malformations, and open posterior neuropores among the survivors. Histological examination of tail buds from treated embryos revealed defects which included total dysplasia of caudal structures, the presence of accessory neural tube and notochord tissue, and abnormal fusions of the notochord to the neural tube and tailgut. The incidence, severity, and location of the defects were dependent on the dose of the teratogen, and the stage of development at the time of treatment. The defects resembled those induced in previous studies by treatment with sialic acid binding lectins such as wheat germ agglutinin and limulus polyphemus lectin (Griffith and Wiley, '90b).     

Multispecies antbird societies in lowland forests of Surinam and Ecuador: stable membership and foraging differences

Flocks of insectivorous birds in the understory of lowland wet forest in Surinam and eastern Ecuador regularly included two species of antshrikes in the genus Thamnomanes ( ardesiacus and caesius ) and four species of antwrens in the genus Myrmotherula (in Surinam, axillaris, menetriesii, longipennis , and gutturalis ; in Ecuador, the first two plus hauxwelli and ornata ) (Formicariidae), as well as a number of other species particularly in the families Furnariidae and Dendrocolaptidae. Each flock included only a pair or occasionally a small group of each species. Although the individuals in a flock often spread over an area 30 m in diameter, the Myrmotherula, Thamnomanes and several other species moved cohesively through the forest. Each flock persisted throughout a day and, over periods of at least a week, recurred within the same largely exclusive range in the forest. The two Thamnomanes species had distinctive vocalizations that provided the primary signals for flock cohesion and alarm calls. Although most of the species of Myrmotherula had loud vocalizations, these were uttered too infrequently to contribute to flock cohesion and played no role in reactions to predators. In Central America, on the other hand, where Thamnomanes does not occur, M. fulviventris produces loud vocalizations, that resemble those of Thamnomanes , during disturbances to a flock. The species of Myrmotherula in each locality segregated ecologically in two dimensions, height of foraging above ground and preference for foraging in live or dead foliage. A shift in the foraging height of axillaris depending on the presence or absence of longipennis in the same flock suggested that competition for food has favoured ecological segregation of foraging height by these species. Thamnomanes–Myrmotherula flocks attain an unusual degree of cohesiveness and integration of foraging specialities in comparison with other mixed aggregations of animals.