Synchrony, waves, and spatial hierarchies in the spread of influenza

Quantifying long-range dissemination of infectious diseases is a key issue in their dynamics and control. Here, we use influenza-related mortality data to analyze the between-state progression of interpandemic influenza in the United States over the past 30 years. Outbreaks show hierarchical spatial spread evidenced by higher pairwise synchrony between more populous states. Seasons with higher influenza mortality are associated with higher disease transmission and more rapid spread than are mild ones. The regional spread of infection correlates more closely with rates of movement of people to and from their workplaces (workflows) than with geographical distance. Workflows are described in turn by a gravity model, with a rapid decay of commuting up to around 100 km and a long tail of rare longer range flow. A simple epidemiological model, based on the gravity formulation, captures the observed increase of influenza spatial synchrony with transmissibility; high transmission allows influenza to spread rapidly beyond local spatial constraints.     

Perceptions of state public health officers and state veterinarians regarding risks of bioterrorism in the United States

OBJECTIVE:To assess perceptions of state public health officers and state veterinarians in the United States regarding the risks of bioterrorism and determine the degree of support provided for activities related to bioterrorism. DESIGN: Cross-sectional survey. SAMPLE POPULATION: State public health officers and state veterinarians. PROCEDURE: A questionnaire was sent between April and June 2001 to the state public health officer and state veterinarian in each of the 50 states and the District of Columbia. RESULTS: Perceptions of the risk of bioterrorism attacks were similar for state public health officers and state veterinarians. Veterinarians perceived the risks associated with foot-and-mouth disease and Newcastle disease to be higher than did physicians. State veterinarians perceived the risks associated with an anthrax hoax, brucellosis, and ricin toxicosis to be lower than did state public health officers. Risk posed by agents that affected animals exclusively was perceived to be higher than risk posed by agents that affected humans exclusively and zoonotic agents. Number of full-time-equivalent positions devoted to bioterrorism surveillance and percentage of the budget devoted to bioterrorism activities were significantly lower for offices run by state veterinarians than for offices run by state public health officers. State veterinarians were significantly less likely to have knowledge of bioterrorism incidents within their state or district than were state public health officers. CONCLUSIONS AND CLINICAL RELEVANCE: Provision of additional resources to state veterinarians and explicit integration of their expertise and surveillance capabilities may be important to effectively mitigate the risk of bioterrorism.     

Bartonella species detection in captive, stranded and free-ranging cetaceans

We present prevalence of Bartonella spp. for multiple cohorts of wild and captive cetaceans. One hundred and six cetaceans including 86 bottlenose dolphins (71 free-ranging, 14 captive in a facility with a dolphin experiencing debility of unknown origin, 1 stranded), 11 striped dolphins, 4 harbor porpoises, 3 Risso's dolphins, 1 dwarf sperm whale and 1 pygmy sperm whale (all stranded) were sampled. Whole blood (n = 95 live animals) and tissues (n = 15 freshly dead animals) were screened by PCR (n = 106 animals), PCR of enrichment cultures (n = 50 animals), and subcultures (n = 50 animals). Bartonella spp. were detected from 17 cetaceans, including 12 by direct extraction PCR of blood or tissues, 6 by PCR of enrichment cultures, and 4 by subculture isolation. Bartonella spp. were more commonly detected from the captive (6/14, 43%) than from free-ranging (2/71, 2.8%) bottlenose dolphins, and were commonly detected from the stranded animals (9/21, 43%; 3/11 striped dolphins, 3/4 harbor porpoises, 2/3 Risso's dolphins, 1/1 pygmy sperm whale, 0/1 dwarf sperm whale, 0/1 bottlenose dolphin). Sequencing identified a Bartonella spp. most similar to B. henselae San Antonio 2 in eight cases (4 bottlenose dolphins, 2 striped dolphins, 2 harbor porpoises), B. henselae Houston 1 in three cases (2 Risso's dolphins, 1 harbor porpoise), and untyped in six cases (4 bottlenose dolphins, 1 striped dolphin, 1 pygmy sperm whale). Although disease causation has not been established, Bartonella species were detected more commonly from cetaceans that were overtly debilitated or were cohabiting in captivity with a debilitated animal than from free-ranging animals. The detection of Bartonella spp. from cetaceans may be of pathophysiological concern.     

Variability in the performance of juvenile Chinook salmon is explained primarily by when and where they resided in estuarine habitats

Estuarine habitats provide rearing opportunities for the juvenile life stage of anadromous fishes. Because survival is positively correlated with juvenile performance, these estuarine habitats play an important role in population abundance and productivity. To provide information for the recovery of several depressed stocks of Chinook salmon in the Columbia River Basin, we sought to identify the factors that explain variability in performance. Using otolith‐derived estimates of juvenile somatic growth rate as an index of recent performance, we observed a negative nonlinear relationship between growth rate and day of year, and a decreasing and increasing trend of growth rate over the 8 years of this study and distance from the river mouth respectively. Using a generalised linear modelling approach, we found that variability in juvenile somatic growth rate was best explained by where and when individuals were collected, their body size, contaminant loads, stock of origin, and whether a fish was hatchery produced or unmarked. Lastly, we argue that a considerable improvement to the growth rate of juveniles in estuarine habitats is physiologically possible. The results of this 8‐year study provide a baseline of the performance of juvenile Chinook salmon to evaluate habitat restoration programs and to compare against future anthropogenic conditions.     

Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor

Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.     

Efficacy of an injectable, sustained-release formulation of moxidectin in preventing experimental heartworm infection in mongrel dogs challenged 12 months after administration

The objective of this study was to ascertain the ability of a single subcutaneous injection of a sustained-release (SR) formulation of moxidectin to protect dogs against challenge inoculation with infective Dirofilaria immitis larvae 364 days after administration. Twenty four purpose-bred adult mixed-breed dogs were grouped into three blocks of eight based on weight and sex. Saline solution (0.9% NaCl) or a moxidectin SR formulation at volumes designed to deliver 0.17 or 0.27 mg moxidectin/kg b.w. was injected subcutaneously on day 0. Throughout the post-treatment period, injection sites of all dogs were periodically examined visually and by palpation. Palpable swellings were characterized as to size, consistency and the presence of associated pain or erythema. On day 364, each dog was inoculated subcutaneously with 50 D. immitis L3. On days 510 and 511, dogs were euthanatized, and their hearts, lungs and thoracic cavities were inspected for the presence of adult heartworms. number, sex and viability of recovered heartworms were determined. The mean number of heartworms recovered from dogs that had received the saline control injection was 35.7. No heartworms were recovered from any dog treated with either 0.17 or 0.27 mg moxidectin/kg b.w. For variable periods of time following treatment, small (1-4 mm diameter), firm, subcutaneous swellings could be palpated at the injection sites of dogs treated with 0.17 or 0.27 mg moxidectin/kg b.w. These swellings contracted progressively and eventually disappeared except for the case of one animal treated with 0.27 mg/kg, in which the swelling persisted for the entire study period. At no time during the study was pain or erythema noted at the injection site of any dog, and no dog exhibited any adverse systemic reaction related to treatment. We conclude that under conditions pertaining in this study, a single subcutaneous injection of a moxidectin SR formulation at dosing rates of either 0.17 or 0.27 mg/kg b.w. can safely protect adult dogs against experimental challenge inoculation with infective heartworm larvae for a period of 12 months.