PubMed Health⌕ Search

Biomedical subjects

David L Smith

Publications and source records attributed to David L Smith.

At least 19 recordsLinked to original sources

Spatial control of rabies on heterogeneous landscapes.

Rabies control in terrestrial wildlife reservoirs relies heavily on an oral rabies vaccine (ORV). In addition to direct ORV delivery to protect wildlife in natural habitats, vaccine corridors have been constructed to control the spread; these corridors are often developed around natural barriers, such as rivers, to enhance the effectiveness of vaccine deployment. However, the question of how to optimally deploy ORV around a river (or other natural barrier) to best exploit the barrier for rabies control has not been addressed using mathematical models. Given an advancing epidemic wave, should the vaccine be distributed on both sides of barrier, behind the barrier, or in front of it? Here, we introduce a new mathematical model for the dynamics of raccoon rabies on a spatially heterogeneous landscape that is both simple and realistic. We demonstrate that the vaccine should always be deployed behind a barrier to minimize the recurrence of subsequent epidemics. Although the oral rabies vaccine is sufficient to induce herd immunity inside the vaccinated area, it simultaneously creates a demographic refuge. When that refuge is in front of a natural barrier, seasonal dispersal from the vaccine corridor into an endemic region sustains epidemic oscillations of raccoon rabies. When the vaccine barrier creates a refuge behind the river, the low permeability of the barrier to host movement limits dispersal of the host population from the protected populations into the rabies endemic area and limits subsequent rabies epidemics.

Administration, Oral↗

Expression of three expansin genes during development and maturation of Kyoho grape berries.

Expansins are cell-wall-localized proteins that induce loosening of isolated plant cell walls in vitro in a pH-dependent manner, but exhibit no detectable hydrolase or transglycosylase activity. Three putative expansin cDNAs, Vlexp1, Vlexp2, and Vlexp3 were isolated from a cDNA library made from mature berries of the Kyoho grape. Expression profiles of the 3 genes were analyzed throughout berry development. Accumulation of the Vlexp3 transcript was closely correlated with berry softening, and expression of this gene was detected before véraison and markedly increased at véraison (onset of berry softening). Expression of Vlexp3 was berry-specific. Vlexp1 and Vlexp2 mRNA accumulation began during the expansion stage of berry development and expression increased for both genes during ripening. Vlexp1 and Vlexp2 mRNA was detected in leaf, tendril and flower tissues and Vlexp2 mRNA was additionally detected in root and seed tissues. These findings suggest that the three expansin genes are associated with cell division or expansion and berry ripening. Vlexp3, in particular, is most likely to play a role in grape berry softening at véraison.

Amino Acid Sequence↗

Key strategies for reducing spread of avian influenza among commercial poultry holdings: lessons for transmission to humans.

Recent avian flu epidemics (A/H5N1) in Southeast Asia and case reports from around the world have led to fears of a human pandemic. Control of these outbreaks in birds would probably lead to reduced transmission of the avian virus to humans. This study presents a mathematical model based on stochastic farm-to-farm transmission that incorporates flock size and spatial contacts to evaluate the impact of control strategies. Fit to data from the recent epidemic in the Netherlands, we evaluate the efficacy of control strategies and forecast avian influenza dynamics. Our results identify high-risk areas of spread by mapping of the farm level reproductive number. Results suggest that an immediate depopulation of infected flocks following an accurate and quick diagnosis would have a greater impact than simply depopulating surrounding flocks. Understanding the relative importance of different control measures is essential for response planning.

Animals↗

Fever in patients with mixed-species malaria.

BACKGROUND: Clinical symptoms of mixed-species malaria infections have been variously reported as both less severe and more severe than those of single-species infections. METHODS: Oral temperatures were taken from and blood slides were prepared for 2308 adults who presented at outpatient malaria clinics in Tak Province (Thailand) during May-August 1998, May-July 1999, and May-June 2001 with malaria infections diagnosed by 2 expert research microscopists, each of whom was blinded to the other's reports. RESULTS: In each year, temperatures of patients with mixed Plasmodium vivax-Plasmodium falciparum infections were higher than temperatures of patients with P. vivax or P. falciparum infections. In every mixed-species case, P. falciparum parasitemia was higher than P. vivax parasitemia, but patient temperature was not correlated with the parasitemia of either species or with the total parasitemia. CONCLUSIONS: Among adults who self-report to malaria clinics in western Thailand, patients with mixed P. vivax-P. falciparum infections have higher fevers than patients with single-species infections, a distinction that cannot be attributed to differences in parasitemia. This observation warrants more detailed investigations, spanning wider ranges of ages and transmission environments.

Adult↗

A high-throughput method for quantifying alleles and haplotypes of the malaria vaccine candidate Plasmodium falciparum merozoite surface protein-1 19 kDa.

BACKGROUND: Malaria vaccine efficacy may be compromised if the frequency of non-target alleles increases following vaccination with a genetically polymorphic target. Methods are needed to monitor genetic diversity in polymorphic vaccine antigens, but determining which genetic variants of such antigens are present in infected individuals is complicated by the frequent occurrence of mixed infections. METHODS: Pyrosequencing was used to determine allele frequencies at each of six single nucleotide polymorphisms in the Plasmodium falciparum blood-stage vaccine antigen merozoite surface protein 1 19 kDa (MSP-119) in field samples from a vaccine-testing site in Mali. Mixtures of MSP-119 clones were created to validate a haplotype-estimating algorithm that uses maximum likelihood methods to determine the most probable combination of haplotypes given the allele frequencies for an infection and the haplotypes known to be circulating in the population. RESULTS: Fourteen unique MSP-119 haplotypes were identified among 351 genotyped infections. After adjustment to a standard curve, Pyrosequencing provided accurate and precise estimates of allele frequencies in mixed infections. The haplotype-estimating algorithm provided accurate estimates of haplotypes in mixed infections containing up to three haplotypes. Based on the MSP-119 locus, approximately 90% of the 351 infections contained two or fewer haplotypes. CONCLUSION: Pyrosequencing in conjunction with a haplotype-estimating algorithm provides accurate estimates of haplotypes present in infections with up to 3 haplotypes, and can be used to monitor genetic diversity in parasite populations prior to and following introduction of MSP-1-based malaria vaccines.

Adult↗

Potential impact of intermittent preventive treatment (IPT) on spread of drug-resistant malaria.

BACKGROUND: Treatment of asymptomatic individuals, regardless of their malaria infection status, with regularly spaced therapeutic doses of antimalarial drugs has been proposed as a method for reducing malaria morbidity and mortality. This strategy, called intermittent preventive treatment (IPT), is currently employed for pregnant women and is being studied for infants (IPTi) as well. As with any drug-based intervention strategy, it is important to understand how implementation may affect the spread of drug-resistant parasites. This is a difficult issue to address experimentally because of the limited size and duration of IPTi trials as well as the intractability of distinguishing the spread of resistance due to conventional treatment of malaria episodes versus that due to IPTi when the same drug is used in both contexts. METHODS AND FINDINGS: Using a mathematical model, we evaluated the possible impact of treating individuals with antimalarial drugs at regular intervals regardless of their infection status. We translated individual treatment strategies and drug pharmacokinetics into parasite population dynamic effects and show that immunity, treatment rate, drug decay kinetics, and presumptive treatment rate are important factors in the spread of drug-resistant parasites. Our model predicts that partially resistant parasites are more likely to spread in low-transmission areas, but fully resistant parasites are more likely to spread under conditions of high transmission, which is consistent with some epidemiological observations. We were also able to distinguish between spread of resistance due to treatment of symptomatic infections and that due to IPTi. We showed that IPTi could accelerate the spread of resistant parasites, but this effect was only likely to be significant in areas of low or unstable transmission. CONCLUSIONS: The results presented here demonstrate the importance of considering both the half-life of a drug and the existing level of resistance when choosing a drug for IPTi. Drugs to which little or no resistance exists are not advisable for IPT in high-transmission areas, but IPTi is not likely to significantly impact the spread of highly resistant parasites in areas where partial resistance is already established. IPTi is more likely to accelerate the spread of resistance in high-transmission areas than is IPT in adults (i.e., pregnant women).

Adult↗

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.

Adult↗

Identifying groups at high risk for carriage of antibiotic-resistant bacteria.

BACKGROUND: No simple, cost-effective methods exist to identify patients at high risk for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci colonization outside intensive care settings. Without such methods, colonized patients are entering hospitals undetected and transmitting these bacteria to other patients. We aimed to develop a highly sensitive, simple-to-administer prediction rule to identify subpopulations of patients at high risk for colonization on hospital admission. METHODS: We conducted a prospective cohort study of adult patients admitted to the general medical and surgical wards of a tertiary-care facility. Data were collected using electronic medical records and an investigator-administered questionnaire. Cultures of anterior nares and the perirectal area were also collected within 48 hours of admission. RESULTS: Among 699 patients who enrolled in this study, 697 underwent nasal cultures; 555, perirectal cultures; and 553, both. Patient self-report of a hospital admission in the previous year was the most sensitive variable in identifying patients colonized with methicillin-resistant Staphylococcus aureus or with either organism (sensitivity, 76% and 90%, respectively). A prediction rule requiring patients to self-report having received antibiotics and a hospital admission in the previous year would have identified 100% of patients colonized with vancomycin-resistant enterococci. In the high-risk groups defined by the prediction rule, the prevalence of colonization by methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, or either organism were 8.1%, 10.2%, and 15.0%, respectively. CONCLUSION: Patients with a self-reported previous admission within 1 year may represent a high-risk group for colonization by methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci at hospital admission and should be considered for targeted active surveillance culturing.

Carrier State↗

The role of institutional epidemiologic weight in guiding infection surveillance and control in community and hospital populations.

BACKGROUND: Institutions such as hospitals, prisons, and long-term care facilities have been identified as focal points for the transmission of emerging infections. Cost-effective control of these infections in large populations requires the identification of optimal subpopulations for targeted infection control interventions. Our objective was to quantify and compare the relative impact that individual institutions or subpopulations have on wider population-level outbreaks of emerging pathogens. DESIGN: We describe a simple mathematical model to compute the epidemiologic weight (EW) of an institution or subpopulation. The EW represents the rate at which newly infectious individuals exit the institution under consideration. SETTING: A hypothetical academic tertiary-care hospital (700 beds, 5-day length of stay [LOS]) and prison (3098 inmates, 27-day LOS). PATIENTS: Individuals entering a hospital in-patient prison ward and nonprisoners entering both medical and surgical intensive-care units and those admitted to the general medical and surgical wards. RESULTS: The recent example of the community-acquired methicillin-resistant Staphylococcus aureus epidemic is used to illustrate the EW calculation. Hospitals and prisons, which often have vastly dissimilar populations sizes and LOSs and might have differing transmission rates, can have comparable EWs and thus contribute equally to an epidemic in the community. CONCLUSIONS: This method highlights the importance of measuring entrance and exit colonization prevalences for the optimal targeting of prevention measures. The EW not only identified superspreader institutions but also ranks them, enabling public health workers to optimize the allocation of resources to places where they are likely to be of most benefit.

Community-Acquired Infections↗

Characterization of alternative oxidase (AOX) gene expression in response to methyl salicylate and methyl jasmonate pre-treatment and low temperature in tomatoes.

Methyl salicylate (MeSA) vapor increased resistance against chilling injury (CI) in freshly harvested pink tomatoes. The expression patterns of alternative oxidase (AOX) before and during the chilling period demonstrated that pre-treatment of tomato fruit with MeSA vapor increased the transcript levels of AOX. We used 4 EST tomato clones of AOX from the public database that belong to two distinctly related families, 1 and 2 defined in plants. Three clones were designated as LeAOX1a, 1b and 1c and the fourth clone as LeAOX2. Using RT-PCR, 1a and 1b genes were found to be expressed in leaf, root and fruit tissues, but 1c was expressed preferentially in roots. RNA transcript from LeAOX1a of AOX subfamily 1 was present in much greater abundance than 1b or 1c. The presence of longer AOX transcripts detected by RNA gel blot analysis in cold-stored tomato fruit was confirmed to be the un-spliced pre-mRNA transcripts of LeAOX1a and LeAOX1b genes. Intron splicing of LeAOX1c gene was also affected by cold storage when it was detected in roots. This alternative splicing event in AOX pre-mRNAs molecules occurred, preferentially at low temperature, regardless of mRNA abundance. Transcript levels of several key genes involved in RNA processing (splicing factors: 9G8-SR and SF2-SR, fibrillarin and DEAD box RNA helicase) were also affected by changes in storage temperature. The aberrant splicing event in AOX pre-mRNA and its possible association with the change in expression of genes involved in RNA processing in tomato fruit having chilling disorder was discussed.

Acetates↗

Children treated at an expeditionary military hospital in Iraq.

OBJECTIVE: To describe the treatment of children at an expeditionary military hospital in wartime Iraq. DESIGN: Descriptive, retrospective study. SETTING: The 332nd Air Force Theater Hospital in Balad, Iraq, January 1, 2004, to May 31, 2005. PATIENTS: All 85 children (of 1626 total patients) evaluated and treated at the hospital during the study period. INTERVENTIONS: Indicated surgical procedures performed on children. MAIN OUTCOME MEASURES: Age, sex, diagnosis, injury, operations, and complications for children during the study period. RESULTS: The 85 children (age range, 1 day to 17 years; mean, 8 years) represented 5.2% of all patients. Thirty-four (61%) of the 56 children for whom sex was recorded were male. Injury was the diagnosis for 48 children (56%). Of these, the cause was fragmentation wound in 25 children (52%), penetrating trauma in 11 (23%), burn in 9 (19%), and blunt trauma in 3 (6%). The site of injury was the lower extremity in 18 children (38%), head in 11 (23%), upper extremity in 8 (17%), abdomen in 8 (17%), and chest in 3 (6%). Nontraumatic conditions had congenital, infectious, gastrointestinal, and neoplastic causes. During the study, 134 operations were performed on 63 children. There were 5 deaths. CONCLUSIONS: Expeditionary military hospitals will encounter both injured and noninjured children seeking medical care. To optimize the care of these children, it will be necessary to provide the proper personnel, training, and equipment.

Adolescent↗

The use of temporary vascular shunts as a damage control adjunct in the management of wartime vascular injury.

BACKGROUND: While the use of vascular shunts as a damage control adjunct has been described in series from civilian institutions no contemporary military experience has been reported. The objective of this study is to examine patterns of use and effectiveness of temporary vascular shunts in the contemporary management of wartime vascular injury. MATERIALS: From September 1, 2004 to August 31, 2005, 2,473 combat injuries were treated at the central echelon III surgical facility in Iraq. Vascular injuries were entered into a registry and reviewed. Location of shunts was divided into proximal and distal, and shunt patency, complications and limb viability were examined. RESULTS: There were 126 extremity vascular injuries treated. Fifty-three (42%) had been operated on at forward locations and 30 of 53 (57%) had temporary shunts in place upon arrival to our facility. The patency for shunts in proximal vascular injuries was 86% (n = 22) compared with 12% (n = 8) for distal shunts (p < 0.05). All shunts placed in proximal venous injuries were patent (n = 4). Systemic heparin was not used and there were no shunt complications. All shunted injuries were reconstructed with vein in theater and early viability for extremities in which shunts were used was 92%. CONCLUSIONS: Temporary vascular shunts are common in the management of wartime vascular injury. Shunts in proximal injuries including veins have high patency rates compared with those placed in distal injuries. This vascular adjunct represents a safe and effective damage control technique and is preferable to attempted reconstruction in austere conditions.

Blood Vessel Prosthesis Implantation↗

Experience with wound VAC and delayed primary closure of contaminated soft tissue injuries in Iraq.

BACKGROUND: Wartime missile injuries are frequently high-energy wounds that devitalize and contaminate tissue, with high risk for infection and wound complications. Debridement, irrigation, and closure by secondary intention are fundamental principles for the management of these injuries. However, closure by secondary intention was impractical in Iraqi patients. Therefore, wounds were closed definitively before discharge in all Iraqi patients treated for such injures at our hospital. A novel wound management protocol was developed to facilitate this practice, and patient outcomes were tracked. This article describes that protocol and discusses the outcomes in a series of 88 wounds managed with it. METHODS: High-energy injuries were treated with rapid aggressive debridement and pulsatile lavage, then covered with negative pressure (vacuum-assisted closure [VAC]) dressings. Patients underwent serial operative irrigation and debridement until wounds appeared clean to gross inspection, at which time they were closed primarily. Patient treatment and outcome data were recorded in a prospectively updated database. RESULTS: Treatment and outcomes data from September 2004 through May 2005 were analyzed retrospectively. There were 88 high-energy soft tissue wounds identified in 77 patients. Surprisingly, for this cohort of patients the wound infection rate was 0% and the overall wound complication rate was 0%. CONCLUSION: This series of 88 cases is the first report of the use of a negative pressure dressing (wound VAC) as part of the definitive management of high-energy soft tissue wounds in a deployed wartime environment. Our experience with these patients suggests that conventional wound management doctrine may be improved with the wound VAC, resulting in earlier more reliable primary closure of wartime injuries.

Bandages↗

Echelons of care and the management of wartime vascular injury: a report from the 332nd EMDG/Air Force Theater Hospital, Balad Air Base, Iraq.

The objective of this report is to provide a contemporary in-theater account on the systematic management of wartime vascular injury. Included are strategies at each echelon of care that affect the treatment of these injuries. In addition, the aim of this report is to present a modern wartime vascular registry describing rates and distribution of injury in what is now a mature military conflict. A 15-month review (September 1, 2004 through December 1, 2005) from the central level III echelon facility in Iraq (332nd EMDG/Air Force Theater Hospital) presented by the in-theater Consultants for Vascular Surgery. During this period 13 460 casualties were treated at or evacuated through our location, 3096 (23%) with battle-related injuries. Vascular injuries comprised 6.6% (N = 209) of battle-related trauma in the following distribution: extremity 79% (n = 166), neck 13% (n = 27), thoracoabdominal 8% (n = 16). Three levels (formerly echelons) of care are active in theater each with strategies that affect vascular injury management: Level 1: use of commercial tourniquets; level 2: use of temporary vascular shunts as damage control adjuncts; and level 3: definitive repair of arterial and venous injuries in theater using autologous vein. Evacuation patterns and the position of the Air Force Theater Hospital have allowed the formation of a contemporary wartime vascular registry. The rate of vascular injury appears increased compared to that of Vietnam with extremity injuries most prevalent. Effective strategies are in place at each of 3 levels of care that affect the management of vascular injury.

Blood Vessels↗

Hyperinfectivity: a critical element in the ability of V. cholerae to cause epidemics?

BACKGROUND: Cholera is an ancient disease that continues to cause epidemic and pandemic disease despite ongoing efforts to limit its spread. Mathematical models provide one means of assessing the utility of various proposed interventions. However, cholera models that have been developed to date have had limitations, suggesting that there are basic elements of cholera transmission that we still do not understand. METHODS AND FINDINGS: Recent laboratory findings suggest that passage of Vibrio cholerae O1 Inaba El Tor through the gastrointestinal tract results in a short-lived, hyperinfectious state of the organism that decays in a matter of hours into a state of lower infectiousness. Incorporation of this hyperinfectious state into our disease model provides a much better fit with the observed epidemic pattern of cholera. These findings help to substantiate the clinical relevance of laboratory observations regarding the hyperinfectious state, and underscore the critical importance of human-to-human versus environment-to-human transmission in the generation of epidemic and pandemic disease. CONCLUSIONS: To have maximal impact on limiting epidemic spread of cholera, interventions should be targeted toward minimizing risk of transmission of the short-lived, hyperinfectious form of toxigenic Vibrio cholerae. The possibility of comparable hyperinfectious states in other major epidemic diseases also needs to be evaluated and, as appropriate, incorporated into models of disease prevention.

Cholera↗

The unexpected importance of mosquito oviposition behaviour for malaria: non-productive larval habitats can be sources for malaria transmission.

BACKGROUND: Mosquitoes commute between blood-meal hosts and water. Thus, heterogeneity in human biting reflects underlying spatial heterogeneity in the distribution and suitability of larval habitat as well as inherent differences in the attractiveness, suitability and distribution of blood-meal hosts. One of the possible strategies of malaria control is to identify local vector species and then attack water bodies that contain their larvae. METHODS: Biting and host seeking, not oviposition, have been the focus of most previous studies of mosquitoes and malaria transmission. This study presents a mathematical model that incorporates mosquito oviposition behaviour. RESULTS: The model demonstrates that oviposition is one potential factor explaining heterogeneous biting and vector distribution in a landscape with a heterogeneous distribution of larval habitat. Adult female mosquitoes tend to aggregate around places where they oviposit, thereby increasing the risk of malaria, regardless of the suitability of the habitat for larval development. Thus, a water body may be unsuitable for adult mosquito emergence, but simultaneously, be a source for human malaria. CONCLUSION: Larval density may be a misleading indicator of a habitat's importance for malaria control. Even if mosquitoes could be lured to oviposit in sprayed larval habitats, this would not necessarily mitigate -- and might aggravate -- the risk of malaria transmission. Forcing mosquitoes to fly away from humans in search of larval habitat may be a more efficient way to reduce the risk of malaria than killing larvae. Thus, draining, fouling, or filling standing water where mosquitoes oviposit can be more effective than applying larvicide.

Animals↗

Capsid structure and dynamics of a human rhinovirus probed by hydrogen exchange mass spectrometry.

Viral capsids are dynamic protein assemblies surrounding viral genomes. Despite the high-resolution structures determined by X-ray crystallography and cryo-electron microscopy, their in-solution structure and dynamics can be probed by hydrogen exchange. We report here using hydrogen exchange combined with protein enzymatic fragmentation and mass spectrometry to determine the capsid structure and dynamics of a human rhinovirus, HRV14. Capsid proteins (VP1-4) were labeled with deuterium by incubating intact virus in D(2)O buffer at neutral pH. The labeled proteins were digested by immobilized pepsin to give peptides analyzed by capillary reverse-phase HPLC coupled with nano-electrospray mass spectrometry. Deuterium levels incorporated at amide linkages in peptic fragments were measured for different exchange times from 12 sec to 30 h to assess the amide hydrogen exchange rates along each of the four protein backbones. Exchange results generally agree with the crystal structure of VP1-4,with extended, flexible terminal and surface-loop regions in fast exchange and folded helical and sheet structures in slow exchange. In addition, three alpha-helices, one from each of VP1-3, exhibited very slow exchange, indicating high stability of the protomeric interface. The beta-strands at VP3 N terminus also had very slow exchange, suggesting stable pentamer contacts. It was noted, however, that the interface around the fivefold axis had fast and intermediate exchange, indicating relatively more flexibility. Even faster exchange rates were found in the N terminus of VP1 and most segments of VP4, suggesting high flexibilities, which may correspond to their potential roles in virus uncoating.

Capsid↗