Peter White

The rise in gonococcal antibiotic resistance and the threat of untreatable infection are focusing attention on strategies to limit the spread of drug-resistant gonorrhea. Mathematical models provide a framework to link the natural history of infection and patient behavior to epidemiological outcomes and can be used to guide research and enhance the public health impact of interventions. While limited knowledge of key disease parameters and networks of spread has impeded development of operational models of gonococcal transmission, new tools in gonococcal surveillance may provide useful data to aid tracking and modeling. Here, we highlight critical questions in the management of gonorrhea that can be addressed by mathematical models and identify key data needs. Our overarching aim is to articulate a shared agenda across gonococcus-related fields from microbiology to epidemiology that will catalyze a comprehensive evidence-based clinical and public health strategy for management of gonococcal infections and antimicrobial resistance.

United Kingdom has reported the largest documented outbreak of lymphogranuloma venereum (LGV), a re-emerging sexually transmitted infection (STI) which is primarily seen in HIV-positive men who have sex with men (MSM). A diagnostic service was established in response to the outbreak linked to a voluntary LGV Enhanced Surveillance system. We examined the performance of this novel surveillance system to identify utility in tracking a re-emerging infection. We described laboratory data on samples and surveillance data from case reports for LGV from 2004-2010. We performed a cross-sectional analysis comparing clinical and behavioural characteristics of HIV-positive and HIV-negative/unknown LGV cases diagnosed in MSM using multivariable logistic regression models with generalised estimating equations to control for repeat infections. LGV Surveillance data were available for 87% (1,370/1,581) of LGV cases (after de-duplication). There were 1,342 episodes in 1,281 MSM, most of whom were kn...

Linear filter theory based on Wiener filtering is well understood and used widely in many fields of image and signal processing. However, the use of linear filters is generally associated with implicit approximations. Therefore, in this work a series of non-linear filters is developed based on the concepts of Volterra series and these are applied to image interpolation problems. More

Millions of domestic and wild European rabbits (Oryctolagus cuniculus) have died in Europe, Asia, Australia and New Zealand during the past 17 years following infection by Rabbit haemorrhagic disease virus (RHDV). This highly contagious and deadly disease was first identified in China in 1984. Epidemics of RHDV then radiated across Europe until the virus apparently appeared in Britain in 1992. However, this concept of radiation of a new and virulent virus from China is not entirely consistent with serological and molecular evidence. This study shows, using RT-PCR and nucleotide sequencing of RNA obtained from the serum of healthy rabbits stored at 4 degrees C for nearly 50 years, that, contrary to previous opinions, RHDV circulated as an apparently avirulent virus throughout Britain more than 50 years ago and more than 30 years before the disease itself was identified. Based on molecular phylogenetic analysis of British and European RHDV sequences, it is concluded that RHDV has almo...

The middle ear pressure was increased by air injections and the level (pressure opening level = Pol) at which the Eustachian tube (ET) opened was determined in anaesthetized ras. At a rate of pressure increase of 0.7 kPa/s it opened at 4.1 +/- 0.4 kPa. A change of the body and head position from horizontal to almost vertical increased the Pol by about 0.4 kPa (head downwards) and decreased the Pol by about 0.3 kPa (head upwards). Epinephrine tested in a dose-response experiment had no significant effect on Pol (doses from 0.01 to 10 micrograms/kg body weight). A surface-tension-lowering substance, Tween 20, instilled into the middle ear, reduced Pol by about 1 kPa. A change in body and head position had thus a moderate effect on the passive opening of the ET, a strong decongestant had no effect, and a surface-lowering substance, a marked effect. With increasing rates of pressure change in the middle ear, Pol increased. After instillation of Tween 20 there was an almost parallel shif...

An experimental rat model for Streptococcus pneumoniae otitis media was used to investigate passive protection by anti-type 3 capsular antibodies and effects of immunization with pneumococcal surface protein A (PspA). Anti-type 3 antibodies instilled into the middle ear reduced purulent otitis media as compared to control animals (p = 0.015). Secondly, after immunization with PspA, the right middle ear was inoculated with S. pneumoniae type 6A in a dose calibrated to induce purulent otitis media. There was an anti-PspA antibody response in all rats immunized and a reduction in signs of purulent otitis media as compared to control animals (p = 0.026). Thus, purulent (acute) otitis media can be reduced by local application of antibodies in the middle ear and also by immunization with a non-type-specific pneumococcal protein, PspA.

Terbutaline, a beta 2-adrenoceptor agonist, was administered subcutaneously to 10 healthy adult subjects. The pressure opening level (Pol) of the Eustachian tube (ET) and the remaining middle ear pressure when the ET closed (Pcl) after passive equilibration were measured as well as parameters for active tubal function. A quantitative impedance method in combination with a pressure chamber was used. Pol was reduced by 0.29 +/- 0.10 (-7.3%) kPa 90 min after injection of terbutaline 5 micrograms/kg body weight. There was also a decrease in Pcl, 0.17 +/- 0.06 kPa (-14.0%). No such decrease was seen after saline solution injected subcutaneously. It is suggested that terbutaline facilitates the ET opening by stimulating the secretion of surface tension lowering substances.

Currently available antigen tests for norovirus (NoV) have excellent specificity but negative results do not always rule out infection. Real-time reverse transcription polymerase chain reaction (RT-PCR) is a useful method for detecting and genotyping NoV in humans and oysters. An outbreak of NoV associated with oyster consumption in northern New South Wales confirmed the value of real-time RT-PCR where immunochromatography (ICT) tests were negative. Eight cases of gastrointestinal illness in northern NSW, clinically suggestive of NoV infection, were associated with consumption of oysters. A joint environmental investigation was conducted by the New South Wales Food Authority and local council. One human sample was collected and tested for NoV using ICT and real-time RT-PCR. Oyster samples were tested for NoV utilising real-time RT-PCR. The patient with a stool sample had NoV genogroup II (GII) confirmed by real-time RT-PCR after testing negative by ICT. Illness in all cases was cons...

Partner notification is the process of providing support for, informing and treating sexual partners of individuals who have been diagnosed with sexually transmitted infections (STIs). It is traditionally undertaken by specialist sexual health services, and may involve informing a partner on a patient's behalf, with consent. With an increasing proportion of STIs diagnosed in general practice and other community settings, there is a growing need to understand the best way to provide partner notification for people diagnosed with a STI in this setting using a web-based referral system. We aimed to compare three different approaches to partner notification for people diagnosed with chlamydia within general practice. Cluster randomised controlled trial. General practices in England and, within these, patients tested for and diagnosed with genital chlamydia or other bacterial STIs in that setting using a web-based referral system. Three different approaches to partner notification: p...

Higher prices for unprotected sex threaten the high levels of condom use that contributed to the decline in Zimbabwe's human immunodeficiency virus (HIV) epidemic. To improve understanding of financial pressures competing against safer sex, we explore factors associated with the price of commercial sex in rural eastern Zimbabwe. We collected and analyzed cross-sectional data on 311 women, recruited during October-December 2010, who reported that they received payment for their most-recent or second-most-recent sex acts in the past year. Zero-inflated negative binomial models with robust standard errors clustered on female sex worker (FSW) were used to explore social and behavioral determinants of price. The median price of sex was $10 (interquartile range [IQR], $5-$20) per night and $10 (IQR, $5-$15) per act. Amounts paid in cash and commodities did not differ significantly. At the most-recent sex act, more-educated FSWs received 30%-74% higher payments. Client requests for con...

Seroadaptive behaviors are strategies employed by men who have sex with men (MSM) to reduce the transmission risk for human immunodeficiency virus (HIV). It has been suggested that they contribute to the increasing diagnoses of sexually transmitted infections in HIV-diagnosed MSM. To understand the context in which the reemerging sexually transmitted infections appear, we developed a social epidemiological model incorporating the multiple factors influencing seroadaptive behaviors. A literature review of seroadaptive behaviors in HIV-diagnosed MSM was conducted. The literature was synthesized using a social epidemiological perspective. Seroadaptive behaviors are adopted by MSM in high-income countries and are a way for HIV-diagnosed men to manage and enjoy their sexual lives. Influences are apparent at structural, community, interpersonal, and intrapersonal levels. There is little evidence of whether and when the behavior forms part of a premeditated strategy; it seems dependent on ...

In the United Kingdom, human immunodeficiency virus (HIV) transmission among men who have sex with men (MSM) is not under control, despite readily available treatment, highlighting the need to design a cost-effective combination prevention package. MSM report significantly reduced transmission risk behavior following HIV diagnosis. To assess the effectiveness of HIV diagnosis in averting transmission during highly infectious primary HIV infection (PHI), we developed a stochastic individual-based model to calculate the number of HIV-transmission events expected to occur from a cohort of recently infected MSM with and those without the behavior changes reported after diagnosis. The model incorporates different types of sex acts, incorporates condom use, and distinguishes between regular and casual sex partners. The impact on transmission in the 3 months after infection depends on PHI duration and testing frequency. If PHI lasts for 3 months and testing is performed monthly, then behav...

Seventy-one percent of the patients would definitely return, and tory settings have found patient factors and process of care 22% would probably return for a repeat FB. Better health status factors that influence patient satisfaction, including age, race, (odds ratio (OR) 1.4; 95% confidence interval (CI), 1.1-1.7), not gender, wait times, and patient-provider communication (20- being bothered by scope insertion

Insoluble, pure protein particles could be advantageous as single-entity vaccines or as carriers for small peptide epitopes. Dense gas anti-solvent precipitation was employed to produce pure protein particles which were found to be insoluble in water. As particulate and multimerized antigens are more immunogenic and hence more advantageous for vaccination, particles were produced via this method using ovalbumin as a model antigen. The particles produced had a mean diameter of approximately 300nm, and remained as discrete particles at low pH. At neutral pH or in the presence of electrolyte, the particles exhibited predictable flocculation behaviour to produce aggregates 1-5microm in diameter. Immunisation of mice with these flocculates elicited specific ovalbumin antibody production, T-cell proliferation and a cytotoxic T-cell response, all in the absence of adjuvant. Thus, dense gas processing could be used as a generic method to produce pure protein particulate vaccines.

Reliable data on sexual behaviour trends are needed to evaluate HIV interventions in sub-Saharan Africa but are difficult to obtain due inter alia to social desirability bias. The objective of this paper is to assess whether the use of informal confidential voting interviews (ICVI) was associated with greater reporting of socially proscribed behavioural risk factors for HIV infection than were conventional interviewing methods. Comparison of changes in reports of risk behaviours for HIV infection in ICVI versus face to face interviews (FTFIs) between the first two rounds of a large scale, longitudinal, population based survey in Manicaland, Zimbabwe. Examination of factors that could contribute to observed changes in the effect of ICVI, including temporal changes in response error and social desirability, and factors affecting statistical power to detect differences between methods-that is, reductions in the prevalence of risk behaviours and sample size. Enhanced reporting of HIV associated risk behaviours in ICVI interviews was not so apparent in the second round as in the first round of the survey, particularly for less frequently reported behaviours. Levels of reported HIV associated risk behaviour and sample sizes both declined between the two survey rounds. The level of response error was higher in ICVI interviews than in FTFI interviews but did not alter over time. ICVI interviews can reduce social desirability bias in data on HIV associated risk behaviours. The extent and direction of change in net reduction in bias over time remains uncertain and will depend on local circumstances.

To explore how the cost effectiveness of a behaviour-change prevention programme for sexually transmitted infection (STI) varies with the phase of an STI epidemic. A model of STI transmission and standard methods of cost-effectiveness analysis was used to examine the cost effectiveness of a hypothetical, behaviour-change intervention initiated at various phases of an STI epidemic. The intervention was more cost effective when initiated in earlier phases of the epidemic rather than later phases, under a range of scenarios. However, the relative impact of the timing of the initiation of the STI prevention intervention on the cost effectiveness was quite small compared with other important factors, such as the cost and impact of the intervention and the lifetime medical cost of the STI. Earlier initiation of an intervention can improve the cost effectiveness of the intervention, although this result does not hold for all possible scenarios.

Page 1. MICROBIAL DRUG RESISTANCE Volume 5, Number 1, 1999 Mary Ann Liebert, Inc. Immunization and Protection in Pneumococcal Otitis Media Studied in a Rat Model K. PRELLNER,1 A. HERMANSSON,1 P. WHITE,1 À. MELHUS,1 and D. BRILES2 ABSTRACT ...

There is substantial national interest in the widening gap in socio-economic inequalities. The aim of this study was to examine time trends in age-specific mortality in Trent Region comparing rates by socio-economic deprivation from 1988 to 1998. Mortality rates from 1988 to 1998 were calculated for each of five deprivation categories (derived using 1991-based enumeration district level Townsend scores) for men and women aged 45-54, 55-64, 65-74 and 75-84 years. Rate ratios (95 per cent confidence intervals) were calculated for the years 1988-1990 and 1996-1998, comparing the most deprived with the least deprived categories. For men aged 45-54, the rate ratio for the most deprived relative to the least deprived category was 2.42 (2.2-2.67) in 1988-1990 and 2.4 (2.17-2.65) in 1996-1998. Amongst women the ratio fell from 2.14 (1.88-2.42) to 1.67 (1.47-1.88). For men aged 55-64, the rate ratio fell from 2.07 (1.95-2.19) to 1.79 (1.67-1.91). For women the fall was from 1.99 (1.84-2.14) to 1.59 (1.46-1.73). For those aged 65-74, the fall was from 1.65 (1.58-1.72) to 1.33 (1.28-1.39) for men and from 1.55 (1.47-1.63) to 1.37 (1.30-1.45) for women. For people aged 75-84, no clear convergence in rates was seen. There appear to be decreases in socio-economic inequalities in mortality between 1988 and 1998 in Trent Region. These trends run counter to those described in the majority of recent literature.

During my public health specialty training I must admit sometimes to a feeling of apprehension before taking on a task. Being invited to review 'Donaldsons' Essential Public Health', which has been in continuous print for 25 years, would qualify as such a situation. This book is now ...

Norwalk-like viruses (NLVs) were detected using a nested reverse transcriptase-polymerase chain reaction (RT-PCR) with primers directed to the RNA polymerase region. Samples were examined from 11 separate outbreaks of gastroenteritis and five sporadic cases of childhood gastroenteritis between 1997 and 2000. Phylogenetic analysis of the 298 bp sequences showed that all strains belong to NLV genogroup II and the majority of the sequenced isolates (30/36) were members of the 95/96-US subset of strains associated with outbreaks recorded worldwide between 1995 and 1996. This was confirmed by analysis of the full length capsid region of a representative Australian isolate. This study demonstrates the usefulness of targeting primers for NLVs to the predominant circulating genotype(s) and confirms the spread of this subtype globally, including the Southern Hemisphere.

The ability of a target-controlled propofol infusion system to provide sedation for patients undergoing assessment of the upper airway during snoring is presented. This technique provides the desired sedation level for induction of snoring and is short acting and readily controllable. We advocate its use in sedation nasal endoscopy.

The principal role of computed tomography (CT) scanning in rhinosinusitis is as a planning investigation for patients requiring functional endoscopic sinus surgery (FESS). The pre-operative scan is used to highlight any potential surgical hazards, and to delineate the extent of disease reducing unnecessary intervention in disease-free areas. It is inappropriate for CT to be used purely as a diagnostic investigation for chronic rhinosinusitis. As concern has been expressed over the steady rise in the referrals for CT of the sinuses, we conducted a retrospective review of all patients having these scans at two CT scanner sites in Scotland during 1993. Of the 162 scans performed for rhinosinusitis, 58 patients (36 per cent) had not had nasendoscopy performed or had a trial of medical treatment. Subsequently, only 61 patients (38 per cent) went on to FESS. The inappropriate use of CT for these patients can be reduced by insisting that nasendoscopy is performed prior to scanning. Furthermore, radiologists and surgeons should audit the number of patients not having FESS after scanning.

It is postulated here that significant amounts of calcium will be mobilized into the plant by the scorching of one old leaf. This postulate was tested using large (6 m) tomato plants in the glasshouse. Brief scorching with a blowlamp was shown to release some 35% of the leaf's water into the plant. A range of measurements was used to estimate the kinetics and magnitude of this flow. The flow was found to carry a pulse of up to 50% of the leaf's total calcium into the plant, probably via the xylem, and was estimated to increase xylem calcium levels transiently by a factor of about 80. The potential value of scorching treatments in combating calcium-deficiency disorders is discussed.

Recent data indicate that multiple hepatitis C virus (HCV) infections (mixed infection, superinfection, and reinfection) are common among injection drug users (IDUs). In this study, we identified and characterized multiple HCV infection episodes among HCV-seronegative IDU prison inmates (n = 488) enrolled in the Hepatitis C Incidence and Transmission Study cohort. Incident HCV infection with detectable HCV RNA was identified in 87 subjects, 48 of whom completed additional follow-up to screen for reinfection or superinfection. All HCV RNA-detectable samples were tested for multiple infection through a series of specifically designed nested reverse-transcription polymerase chain reaction (nRT-PCR) with sequencing and HCV RNA level measurement. Sequencing revealed that 22 of 87 (25.3%) subjects were infected by two or more viruses. Nine (10.3%) subjects were designated as prevalent cases of incident mixed infection, because two distinct HCV strains were detected at the first viremic time point. Fifteen further cases of multiple HCV infection (superinfection or reinfection) were identified, two of which also showed baseline incident mixed infections. The incidence of new HCV infection (superinfection and reinfection) during follow-up was 40/100 person-years (95% confidence interval, 33-44/100 person-years). Spontaneous clearance of viruses from one subtype and persistence of the other subtype after mixed infection was observed in eight subjects. In these subjects, the virus with higher HCV RNA levels superseded the other. This study comprehensively analyzed frequent multiple HCV infections in a high-risk cohort and provides further insight into infection dynamics and immunity after exposure to variant viral strains. The data presented suggest that HCV RNA levels play an important role in viral competition.

Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease suscepti...

... Below thebaine levels of 25 (ww) the diamorphine absorbance ratios were only weakly influenced by thebaine as shown below: Az7s Az6o Az7s Azas Az,.s Azao Diamorphine 2.20 0.74 0.26 Diamorphine thebaine (75:25) 2.13 0.74 0.27 Thebaine 1.58 0.91 0.46 A275 A260 2. 0 ...

... Gordon Luikart, 1 Marty Kardos, 1 Vanessa Ezenwa, 1 PJ White, 2 Paul Cross, 3 ... Edwards, Robert Garrott, Sara Gregory, Ken Hamlin, Matthew Kauffman, Doug McWhirter, Jarod Rodgerson, Karen Rudolf, Josh Rydalch, Brandon Scurlock, John Stevenson, Rick Wallen, and ...

In November 1973 Newcastle disease suddenly appeared in Northern Ireland, where the viscerotropic disease had not been seen in 3 1/2 years and the two Irelands had been regarded as largely disease free for 30 years. It was successfully controlled with only 36 confirmed affected layer flocks, plus 10 more slaughtered as 'dangerous contacts'. Contemporary investigations failed to reveal the source of the Irish epidemic. Using archival virus samples from most of the affected flocks, RT PCR was conducted with primers selected for all six NDV genes. Phylogenetic analyses of three genes, HN, M and F, confirmed vaccine as the cause of one of the outbreaks. The other six samples were identical and closely related to previous outbreaks in the United States and western Europe initiated by infected imported Latin American parrots. The probable cause of the epidemic followed from the importation from The Netherlands of bulk feed grains contaminated with infected pigeon faeces.

The UK was one of few European countries to document a substantial wave of pandemic (H1N1) 2009 influenza in summer 2009. The First Few Hundred (FF100) project ran from April-June 2009 gathering information on early laboratory-confirmed cases across the UK. In total, 392 confirmed cases were followed up. Children were predominantly affected (median age 15 years, IQR 10-27). Symptoms were mild and similar to seasonal influenza, with the exception of diarrhoea, which was reported by 27%. Eleven per cent of all cases had an underlying medical condition, similar to the general population. The majority (92%) were treated with antiviral drugs with 12% reporting adverse effects, mainly nausea and other gastrointestinal complaints. Duration of illness was significantly shorter when antivirals were given within 48 h of onset (median 5 vs. 9 days, P=0.01). No patients died, although 14 were hospitalized, of whom three required mechanical ventilation. The FF100 identified key clinical and epidemiological characteristics of infection with this novel virus in near real-time.

The United Kingdom implemented a containment strategy for pandemic (H1N1) 2009 through administering antiviral agents (AVs) to patients and their close contacts. This observational household cohort study describes the effect of AVs on household transmission. We followed 285 confirmed primary cases in 259 households with 761 contacts. At 2 weeks, the confirmed secondary attack rate (SAR) was 8.1% (62/761) and significantly higher in persons <16 years of age than in those >50 years of age (18.9% vs. 1.2%, p<0.001). Early (<48 hours) treatment of primary case-patients reduced SAR (4.5% vs. 10.6%, p = 0.003). The SAR in child contacts was 33.3% (10/30) when the primary contact was a woman and 2.9% (1/34) when the primary contact was a man (p = 0.010). Of 53 confirmed secondary case-patients, 45 had not received AV prophylaxis. The effectiveness of AV prophylaxis in preventing infection was 92%.