Biomedical subjects

Steve Leach

Publications and source records attributed to Steve Leach.

8 recordsLinked to original sources

PubMed2006

Importation of exotic ticks into the United Kingdom via the international trade in reptiles.

Due to the increased trade in exotic reptiles, many of which are infested with ticks of various genera, there is an increased risk of exotic ticks and pathogens being introduced and potentially becoming established in new geographical areas. Despite the number and variety of tick species collected from reptiles, their role in the maintenance of pathogens and transmission to humans has not been fully investigated for all species. The potential public health risks to the United Kingdom have been examined through a preliminary study involving the collection and identification of exotic tick species imported via the reptile trade. Reptiles imported into Heathrow Airport, London (July 2003-October 2004) were carefully examined for ectoparasites. Five species of tick were collected: Aponomma exornatum, Ap. latum, Amblyomma rotundatum, Am. dissimile and Am. nuttalli. This is the first report of Am. dissimile identified from an interception at Heathrow airport. The potential for establishment of exotic ticks in the UK and the public health risks are discussed.

Animals↗

PubMed2005

Phase I trial of Orzel (UFT plus leucovorin), cisplatin, and radiotherapy in the treatment of potentially resectable esophageal cancer.

PURPOSE: Fluorinated pyrimidines have been established as radiosensitizers in the combined modality therapy of esophageal cancer. UFT, an oral combination of a 5-fluorouracil pro-drug (uracil) and a dihydropyrimidine dehydrogenase inhibitor (ftorafur), may provide improvement in the ease of administration with equal efficacy. This Phase I study was designed to determine the maximal tolerated dose and dose-limiting toxicity of UFT, leucovorin, and cisplatin when given with radiotherapy in the neoadjuvant treatment of resectable esophageal cancer. METHODS: Chemotherapy consisted of i.v. cisplatin 80 mg/m(2) (Days 1 and 22) and UFT with leucovorin orally on Days 1-35. UFT was escalated in 50-mg/m(2) increments, starting at 200 mg/m(2)/d. Radiotherapy consisted of 4500 cGy in 25 fractions. Patients underwent resection 4-6 weeks after chemoradiotherapy. RESULTS: Ten patients with resectable esophageal cancer were enrolled. Of the 7 patients entered at dose level 1, 1 developed a dose-limiting toxicity of nausea. All 3 patients entered at dose level 2 developed dose-limiting toxicity. The maximal tolerated dose for UFT was the starting level, 200 mg/m(2)/d. Of the 10 patients enrolled, 8 underwent esophagectomy and 2 developed progressive disease and did not undergo surgery. The disease of 6 of the 8 patients was downstaged at surgery. CONCLUSION: The recommended UFT dose for Phase II studies is 200 mg/m(2)/d given orally in two divided doses when given with leucovorin, cisplatin, and radiotherapy.

Adenocarcinoma↗

PubMed2005

Surveillance and control measures during smallpox outbreaks.

We reviewed historical data from 2 smallpox outbreaks in Liverpool and Edinburgh during the early and middle years of the 20th century to assess their contribution to developing modern strategies for response to a deliberate release of smallpox virus. Reports contemporaneous to these outbreaks provide detail on the effectiveness of public health interventions. In both outbreaks, extensive contact tracing, quarantine, and staged vaccination campaigns were initiated, and the outbreaks were controlled within 15 months and 3 months, respectively. In Edinburgh, the number of fatalities associated with vaccination exceeded the number of deaths from the disease. In Liverpool, ambulatory, vaccine-modified cases and misdiagnosis as chickenpox resulted in problems with outbreak control. The relatively slow spread of smallpox, as exemplified by the report from Liverpool, allowed for effective implementation of targeted intervention methods. Targeted surveillance and containment interventions have been successful in the past and should be explored as alternatives to mass vaccination.

Adolescent↗

PubMed2005

Potential impact of antiviral drug use during influenza pandemic.

The recent spread of highly pathogenic strains of avian influenza has highlighted the threat posed by pandemic influenza. In the early phases of a pandemic, the only treatment available would be neuraminidase inhibitors, which many countries are considering stockpiling for pandemic use. We estimate the effect on hospitalization rates of using different antiviral stockpile sizes to treat infection. We estimate that stockpiles that cover 20%-25% of the population would be sufficient to treat most of the clinical cases and could lead to 50% to 77% reductions in hospitalizations. Substantial reductions in hospitalization could be achieved with smaller antiviral stockpiles if drugs are reserved for persons at high risk.

Adolescent↗

PubMed2004

Epidemiologic determinants for modeling pneumonic plague outbreaks.

Pneumonic plague poses a potentially increasing risk to humans in plague nonendemic regions either as a consequence of an aerosolized release or through importation of the disease. Pneumonic plague is person-to-person transmissible. We provide a quantitative assessment of transmissibility based on past outbreaks that shows that the average number of secondary cases per primary case (R0) was 1.3 (variance = 3.1), assuming a geometric probability distribution, prior to outbreak control measures. We also show that the latent and infectious periods can be approximated by using lognormal distributions with means (SD) of 4.3 (1.8) and 2.5 (1.2) days. Based on this parameter estimation, we construct a Markov-chain epidemic model to demonstrate the potential impact of delays in implementing outbreak control measures and increasing numbers of index cases on the incidence of cases in simulated outbreaks.

Disease Outbreaks↗

PubMed2003

Planning for smallpox outbreaks.

Mathematical models of viral transmission and control are important tools for assessing the threat posed by deliberate release of the smallpox virus and the best means of containing an outbreak. Models must balance biological realism against limitations of knowledge, and uncertainties need to be accurately communicated to policy-makers. Smallpox poses the particular challenge that key biological, social and spatial factors affecting disease spread in contemporary populations must be elucidated largely from historical studies undertaken before disease eradication in 1979. We review the use of models in smallpox planning within the broader epidemiological context set by recent outbreaks of both novel and re-emerging pathogens.

Bioterrorism↗

PubMed2000

Invasiveness in chickens, stress resistance and RpoS status of wild-type Salmonella enterica subsp. enterica serovar typhimurium definitive type 104 and serovar enteritidis phage type 4 strains.

The heat and acid resistance and the ability to survive airdrying on commonly used kitchen surfaces were assessed for clinical and environmental strains of Salmonella enterica subsp. enterica serovar Typhimurium, definitive type (DT) 104. Three out of thirty-eight strains of DT 104 were found to be more sensitive in stationary phase to the stresses examined than the other strains. This compares to a previous study by the authors which showed that seven out of forty serovar Enteritidis phage type (PT) 4 strains were more sensitive. RpoS activity was examined indirectly in selected strains of DT 104 and PT 4. In those with normal stress resistance a 100-fold induction of an RpoS-dependent spvR/A:'::luxCDABE fusion was observed upon entry into stationary phase. The sensitive strains examined showed either no induction or a reduced level of spvR/A:'::luxCDABE expression. The rpoS gene was sequenced from these strains and three were found to harbour mutations including one deletion, one base-pair substitution resulting in a nonsense codon, and one insertion causing a frameshift resulting in an early stop codon. Strains with negligible or reduced spvR/A:'::luxCDABE expression had low stress resistance. All strains of DT 104 could be recovered from liver and spleen tissues of infected hens 14 d post-infection, but one with no induction of spvR/A:'::luxCDABE expression was significantly less likely to be recovered from chicken reproductive tissues, liver or spleen than the majority of other strains, including one with reduced spvR/A:'::luxCDABE expression. This work has demonstrated that clinical and environmental strains of DT 104 and PT 4 not infrequently harbour mutations in the rpoS allele. It is possible that the rpoS mutations may have occurred during the initial isolation of the strains. The ability of a strain to cause infection, however, also depends on factors such as host susceptibility and dose.

Animals↗

PubMed1999

Different invasion phenotypes of Campylobacter isolates in Caco-2 cell monolayers.

The pathogenesis of campylobacter enteritis is not well understood, but invasion into and translocation across intestinal epithelial cells may be involved in the disease process, as demonstrated for a number of other enteric pathogens. However, the mechanisms involved in these processes are not clearly defined for campylobacters. In this study, isolates were compared quantitatively in established assays with the enterocyte-like cell line, Caco-2, to determine the extent to which intracellular invasion contributes to translocation across epithelial cell monolayers, and whether isolates vary in this respect. Ten fresh Campylobacter isolates were compared and shown to differ in invasiveness by a factor of 10-fold by following their recovery from gentamicin-treated Caco-2 cells grown on nonpermeable tissue-culture wells. Four of these isolates with contrasting invasive ability were also shown to vary in their ability to translocate across Caco-2 cells grown on semipermeable Transwell inserts by a factor >10. However, translocation did not quantitatively correlate with the intracellular invasiveness of these isolates. Isolate no. 9752 was poorly invasive but had modest translocation ability, isolate no. 10392 was very invasive but did not translocate significantly and remained within the monolayer, isolate no. 9519 both translocated and invaded well, whereas, isolate no. 235 translocated very efficiently but was poorly invasive. Isolate no. 9519 also uniquely caused a transitory flattening of the Caco-2 cells and a possible drop in trans-epithelial electrical resistance (TEER) of the Transwell monolayers, whereas isolate no. 235 did not show these effects. Together these data demonstrate that there are significantly different 'invasion' phenotypes among Campylobacter strains involving different degrees of intracellular invasion, and either different rates of transcellular trafficking or, alternatively, paracellular trafficking.

Animals↗