Rotavirus vaccines: past, present, and future.
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Biomedical subjects
Publications and source records attributed to M A Widdowson.
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OBJECTIVE: To describe the clinical, epidemiologic and microbiological features of a large outbreak of infection with a multiresistant Salmonella enterica serotype Typhimurium definitive type DT204b infection involving at least 392 people in five European countries. METHODS: Icelandic public-health doctors responded to a report on an Internet news site of an outbreak of infection with a multiresistant strain of Typhimurium DT104 in England by contacting the Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC). An international alert was sent out through Enter-net. All strains from England & Wales, The Netherlands, Scotland and Germany, and 17 of the outbreak isolates from Iceland, were phage-typed, screened for antimicrobial resistance, and subjected to molecular typing. Hypothesis-generating interviews were conducted, followed by case-control studies performed in Iceland and England. RESULTS: Isolates from cases in Iceland, England and Wales, The Netherlands, Scotland and Germany were identified as Typhimurium DT204b. The antimicrobial resistance pattern was ACGNeKSSuTTmNxCpL. All strains tested displayed an identical plasmid profile. Strains from five cases in England & Wales and five cases in Iceland possessed identical pulsed-field profiles. Although a common source was suspected, only Iceland implicated imported lettuce as a vehicle, with an analytic epidemiologic study (OR = 40.8; P = 0.005; 95% CI 2.7-3175). CONCLUSION: The identification of international outbreaks, necessary for investigation and control, can be facilitated by standardized phage-typing techniques, the electronic transfer of molecular typing patterns, formal and informal links established through international surveillance networks, and the early reporting of national outbreaks to such networks.
Two surveillance systems exist in the Netherlands to monitor hepatitis C (HCV) infections. Aggregated weekly laboratory data have been available since 1990. In 1999, HCV infection became a notifiable disease. Data showed the number of reported cases has remained stable. Male cases predominated (66%), mainly between age 15 to 54. Injecting drug use was the main route of transmission (64%). Despite its added value, the notifiable system should include more clinical data to better scrutinize future changes in transmission patterns.
Results of the Dutch laboratory surveillance of bacterial gastroenteritis between 1991 and 2001 are presented and compared with recent findings in general practices and in the community. Between 1996 and 2000 the mean annual number of stools screened by sentinel laboratories was about 1000 samples/100,000 inhabitants, which is 4% of the estimated annual incidence of gastroenteritis in the Dutch population. Campylobacter (36/100,000 inhabitants) and salmonella (24/100,000 inhabitants) were the main pathogens isolated. Since 1996, the incidence of laboratory confirmed salmonellosis decreased by 30%, predominantly among young children. The incidence of campylobacter was highest in urban areas and Salmonella Enteritidis emerged as the predominant serotype in urban areas. Between 1991 and 2001, multi-resistant Salmonella Typhimurium DT104 emerged to comprise up to 15% of all salmonella isolates in 2001. Reported rates of Shigella spp. and Yersinia spp. varied little, with average annual incidences of 3.2 and 1.2 cases/100,000 inhabitants, respectively. Escherichia coli O157 (90% STEC) was scarcely found (0.26/100,000).
We investigated which vaccination schedule gives best protection to the vaccinating population, in case there is a measles epidemic in an area with low vaccine coverage. We considered combinations of an early measles vaccination (none, at 6 months or at 9 months), a measles-mumps-rubella (MMR) vaccination around the first birthday (at either 11 or 14 months), and MMR vaccination at an older age (at either 4 or 9 years). The different estimates on measures of protection (percentage of susceptibles, number of reported cases in an epidemic year, percentage of lifetime spent susceptible) relied on a mathematical model of decline of maternal antibody levels with age, and the impact of that antibody level on seroconversion and immunity. Model parameters were estimated from a Dutch population-based serological survey on measles antibodies. Different measures of protection favoured different vaccination schedules, but dropping the age of second MMR vaccination prevents considerably more cases than an extra early measles vaccination or dropping the age of first MMR vaccination.
A survey of 100 rural households in a village in the Chaco region of Bolivia revealed a serious problem of Taenia solium cysticercosis, with a seroprevalence of 99/447 (22%) in humans and 102/273 (37%) in pigs. Risk factors for humans were being in older age groups, absence of sanitary facilities, poor formal education and inability to recognise infected pork. Significant risk indicators were a history of seizures and the reported elimination of worms in the faeces. Risk factors for pigs were being in older age groups and absence of sanitary facilities in the owner's house. The proportion of households with evidence of human cysticercosis was similar for those who owned pigs (48%) and those that did not (55%). This unexpected finding was attributed to the high overall prevalence of cysticercosis in pigs and the probability that everyone, regardless of pig-ownership, had ample opportunity to become infected in such communities. The main recommendation for reducing the prevalence of human cysticercosis was to provide more effective education campaigns, aimed at preventing both T. solium infection and cysticercosis.
Three existing technologies (source containment, source reduction, and monitored natural attenuation) are integrated in barrier-controlled monitored natural attenuation (BCMNA)--a new approach for managing plumes of contaminated groundwater and remediating contaminated sites. The basic BCMNA concept uses a low-permeability, nonreactive barrier to release contaminants into an aquifer at a rate that optimizes natural attenuation. A simplified, one-dimensional model of the process is developed, and a hypothetical example of BCMNA is presented for a site contaminated with benzene. The analytical solution is used to demonstrate how contaminant concentrations can be controlled at a downgradient point of environmental compliance by manipulating design variables. BCMNA provides a greater degree of process control and risk reduction than monitored natural attenuation alone. BCMNA also holds promise for reducing remediation costs because (1) barriers can be constructed relatively inexpensively and (2) a cost-effective amount of source reduction can be applied inside the contained area with the BCMNA system remaining in place to safely complete the remediation process after source reduction is terminated. Further numerical modeling and a demonstration project are recommended to address important details and prove the concept.
In situ stimulation of denitrification has been proposed as a mechanism to remediate groundwater nitrate contamination. In this study, sodium formate was added to a sand and gravel aquifer on Cape Cod, MA, to test whether formate could serve as a potential electron donor for subsurface denitrification. During 16- and 10-day trials, groundwater from an anoxic nitrate-containing zone (0.5-1.5 mM) was continuously withdrawn, amended with formate and bromide, and pumped back into the aquifer. Concentrations of groundwater constituents were monitored in multilevel samplers after up to 15 m of transport by natural gradient flow. Nitrate and formate concentrations were decreased 80-100% and 60-70%, respectively, with time and subsequent travel distance, while nitrite concentrations inversely increased. The field experiment breakthrough curves were simulated with a two-dimensional site-specific model that included transport, denitrification, and microbial growth. Initial values for model parameters were obtained from laboratory incubations with aquifer core material and then refined to fit field breakthrough curves. The model and the lab results indicated that formate-enhanced nitrite reduction was nearly 4-fold slower than nitrate reduction, but in the lab, nitrite was completely consumed with sufficient exposure time. Results of this study suggest that a long-term injection of formate is necessary to test the remediation potential of this approach for nitrate contamination and that adaptation to nitrite accumulation will be a key determinative factor.
A cross-sectional study was done of seroprevalence of Babesia bigemina, B.bovis, and Anaplasma marginale in cattle from eastern Bolivia, to characterise the risk of tick-borne disease in three ecological zones. Nineteen farms were sampled in the subtropical humid zone, 13 in the dry subtropical zone and nine in the lower western valleys of the Andean massif. The enzyme-linked immunosorbent assay was used. All three pathogens were widespread. For B. bovis, seroprevalences were high (75-78%) in the two subtropical zones which thus had low risk of disease from this infection; but the western valleys were endemically unstable with higher risk. For B. bigemina, seroprevalences were lower (24-57%) in the two subtropical zones and thus these areas were endemically unstable for disease from this infection. However, the seroprevalence of B. bigemina in the western valleys was too low (13%) for risk of disease in susceptible cattle to be considered high. For A. marginale, the seroprevalences in the two subtropical zones were low (19-32%) and very low (6%) in the western valleys suggesting all these zones were endemically unstable for anaplasmosis. Data for individual farms were analysed for risk of both forms of babesiosis; this showed low risk of disease in the subtropical humid zone, higher risk in the dry subtropical zone and variable risk in the western valleys.
A P[6]G9 group-A rotavirus caused a protracted hospital outbreak of neonatal diarrhoea in The Netherlands. The outbreak lasted 5 months with 52 cases and an average attack rate of 40%, 46 cases were in an incubator section for neonates under 1 month of age. Rotavirus P161G9 was detected by RT-PCR in stool samples from the 31 cases tested. Emergence of this genotype in Europe may have implications for neonates lacking protective maternal antibodies and for the development of rotavirus vaccines.
Mathematical development and model application is provided for a multiple substrate, sequential electron acceptor model, accounting for hydrodynamic transport, adsorption, and sequential oxygen/iron(III)-based biodegradation. Equations for iron(III)-based biodegradation of petroleum hydrocarbons are developed based on oxygen-inhibited Monod kinetics. The iron(III)-based biodegradation expressions were combined with earlier work by Widdowson and Aelion, to develop the two-dimensional, multiple substrate, oxygen/iron(III) sequential electron acceptor biodegradation model presented here. In addition to mathematical model development, simulations demonstrating the advantages of sequential electron acceptor and multiple substrate biodegradation models are provided. These simulations show that commonly-used single electron acceptor models may underpredict natural, in situ biodegradation potential at sites where indigenous microorganisms are capable of using multiple electron acceptors. Additional simulations show that, for contaminant plumes composed of constituents which biodegrade at different rates and under varying electron acceptor conditions, a multiple substrate model may allow more accurate prediction of both individual contaminant concentrations and the total amount of biodegraded contaminant. Considering that typical contaminant plumes are composed of multiple constituents with varying biodegradation properties and health risks, multiple substrate sequential electron acceptor models have the potential to provide more accurate tracking of individual constituent migration. The model was applied to a leaking UST site in Laurel Bay, South Carolina. Laboratory and monitoring well data presented in Landmeyer et al. have established that the petroleum hydrocarbon contaminants are present in the groundwater and are undergoing sequential oxygen-iron(III)-based biodegradation. Model simulations proved capable of reproducing the trends observed at the Laurel Bay site in that BTX contaminants were removed by sequential biodegradation, occurring first aerobically and subsequently anaerobically, and that iron(III)-reducing organisms biodegrade contaminants only in the absence of oxygen. The BTX compounds were individually but simultaneously modeled, allowing explicit modeling of specific contaminant biodegradation properties (e.g., toluene and xylene are assumed to degrade sequentially and benzene is assumed to degrade aerobically only). Although simulations presented here can reproduce trends observed at the Laurel Bay site, inclusion of additional electron acceptors and additional model calibration to data from this and other sites is necessary to improve and verify the model's capability to predict the efficacy of intrinsic biodegradation of petroleum hydrocarbon contaminants in groundwater.
Basic haematological values were obtained in the field from shot, clinically normal, wild East African ungulates. The species studied were: Thomson's gazelle (Gazella thomsonii), Grant's gazelle (Gazella grantii), blue wildebeest (Conochaetes taurinus), Coke's hartebeest (Alcelaphus buselaphus cokii), impala (Aepyceros melampus) and Burchell's zebra (Equus burchelli). Red cell parameters compared well with previous reports although the mean cell haemoglobin concentrations were higher. The white cell counts were considerably lower in all species. The red and white cells of all species studied had standard mammalian morphology. Generally, the field equipment used worked well under the conditions encountered, although the field microscope made cell counting troublesome and the heat made the preservation of fixed slides difficult.
The relationship between halflife (t1/2, minutes) of oxytetracycline and bodyweight (W, kg) between species of mammals and birds was examined using data collected from the literature. Linear regression of the logarithm of the halflife of the elimination phase of oxytetracycline following intravenous injection on the logarithm of bodyweight for a variety of species of mammals and birds revealed a significant correlation between species (r = 0.602, n = 13, P less than 0.05). The interspecies relationship was described by the allometric equation; t1/2 = 160 W0.20. This suggests that there is about a 14-fold variation in t1/2 across the size range of terrestrial homoeotherms, and provides a guide to dosage regime for species in which oxytetracycline kinetics have not been studied.
A cross-sectional survey for seropositivity to cysticercosis of pigs in the Yucatan Peninsula, Mexico, was carried out in 1996 together with a standardized questionnaire on predetermined individual pig and household risk factors for porcine infection. Serum samples from 697 pigs were analysed by immunoblot for antibodies to Taenia solium cysticercosis and questionnaires from 227 households in 18 villages were collected. All the data were analysed using multivariate analytical techniques taking household clustering into account. The overall porcine seroprevalence in the area was found to be 29%. The most important risk factors for seropositivity in pigs were presence versus absence of a toilet (adjusted odds ratio [adj. OR] 2.37, P = 0.005), crowded households (adj. OR 1.75, P = 0.034) and both corralling (adj. OR 2.14, P = 0.017) and letting pigs loose (adj. OR 2.32, P = 0.035) versus tying them up. There was evidence of clustering at household level and that possible risk factors at municipal or village level may also interact with higher risk management practices such as allowing pigs to run loose.
A three-dimensional solute transport model with biological reactions is presented for simulating the natural attenuation study (NATS) at the Columbus Air Force Base in eastern Mississippi. NATS consisted of the release of a petroleum-based nonaqueous phase liquid (NAPL) and subsequent monitoring of BTEX (benzene, toluene, ethylbenzene, p-xylene), naphthalene, decane, and bromide in a shallow, unconfined aquifer. Conceptual and mathematical models were developed for NAPL source release, sequential aerobic/anaerobic biodegradation, and sorption during NATS. A multiple species, solute transport code (SEAM3D) was used to simulate fully three-dimensional transport and aerobic, nitrate-reducing, ferrogenic, and methanogenic hydrocarbon biodegradation. Simulation results matched individual BTEX concentration distributions collected five- and nine-months following NAPL release. SEAM3D mass-balance calculations at t = nine months indicated that 49% of the hydrocarbon mass that dissolved into the aqueous phase was consumed by biodegradation, 13% of this mass was sorbed, and the remaining 38% was present in the aqueous phase. Mass calculations at t = nine months further indicated that aerobic biodegradation accounted for the majority of hydrocarbon biodegradation (46% of the biodegraded mass), followed by ferrogenesis (28%), nitrate-reduction (21%), and methanogenesis (5%). Model results were particularly sensitive to the NAPL release rate, the initial ferric iron (Fe[III]) concentration, hydrocarbon utilization rates, initial condition for the anaerobic microbial populations, and dispersivity.