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Genomic profiles were obtained for 76 strains of Campylobacter jejuni isolated from bacteraemic patients in England and Wales over the period 1981–94. Genotyping was performed by restriction fragment length polymorphism (RFLP) analysis using a random cloned DNA probe, and by ribotyping with a PCR-generated C. jejuni 16S ribosomal DNA probe. Phenotypic characterization was achieved by heat-stable (HS) and heat-labile (HL) serogrouping, and Preston phagetyping and biotyping. The blood isolates were genomically heterogenous, with 24 RFLP/16S profiles occurring within the 76 strains. Forty-four percent of isolates belonged to one of three RFLP/16S genotypes, reflecting the patterns seen in faecal isolates, except that genotypes usually associated with the HS 1 antigen were uncommon. The two most prevalent genotypes, characteristic of HS 2 and HS 4 strains, showed similarity by cluster analysis. Further evidence was seen of associations between phenotypic and genotypic characters within some HS serogroups. Chromosomal profiling by RFLP analysis does not indicate that particular genotypes have a predisposition to invade the bloodstream.
Cattle were vaccinated with differing doses of an equal mixture of capripox-rinderpest recombinant viruses expressing either the fusion protein (F) or the haemagglutinin protein (H) of rinderpest virus. Animals vaccinated with 2 × 104 p.f.u. or greater of the combined viruses were completely protected against challenge, 1 month later, with both virulent rinderpest and lumpy skin disease viruses. Vaccination with any of the doses did not induce any adverse clinical response in the animals or transmission of the vaccine virus between animals. All cattle challenged 6 or 12 months after vaccination with 2 × 105 p.f.u. of the mixture of recombinant viruses were protected from severe rinderpest disease. Ten out of 18 were completely protected while the remaining 8 developed mild clinical signs of rinderpest. Cattle vaccinated with the recombinant vaccines after prior infection with the parental capripox virus showed more marked clinical signs of rinderpest after challenge with virulent rinderpest, but 9 out of 10 recovered, compared with 80% mortality in the unvaccinated controls.
An anonymized point-prevalence survey of methicillin-resistant Staphylococcus aureus (MRSA) carriage was conducted amongst a stratified random sample of nursing home residents in Birmingham, UK, during 1994. Microbiological sampling from noses, fingers and the environment was undertaken. Information about potential risk factors for the acquisition of MRSA was gathered. MRSA was isolated from cultures of the nose or fingers of 33 of the 191 residents who took part in the study (17%) but only 1 of the 33 positive residents had a clinical infection. Although just 10 of the 87 environmental samples were MRSA positive, there was some environmental contamination in most homes. Risk factors for MRSA carriage were hospital admission within the last year (relative prevalence 2·09, 95% CI 1·13–3·88; P < 0·05) and surgical procedures within the last year (relative prevalence 4·02, 95% CI 2·18–7·43; P = 0·002). Phage-typing of the strains revealed similarities with those circulating in Birmingham hospitals. These findings suggest that the prevalence of MRSA in nursing homes in Birmingham was high, and that the strains may have originated in hospitals.
Laboratory-based surveillance of invasive pneumococcal infections in adults in Finland from 1983 to 1992 identified 862 episodes of pneumococcal bacteraemia and 97 episodes of meningitis. The overall incidence of invasive pneumococcal infections was 9·1 per 100000 for all adults per year, but 27·1, 35·8, and 44·5 per 100000 in those aged 65 years or over, 75 years or over, and 85 years or over, respectively. Most (99·7%) of the pneumococcal strains were sensitive to penicillin. Ninety-five percent of the strains belonged to serogroups/types present in the 23-valent pneumococcal polysaccharide vaccine. Group/type distribution was different in patients aged 16–64 years compared to those 65 years or over (P < 0·001), in bacteraemia compared to meningitis (P < 0·001), and in the years 1983–7 compared to 1988–92 (P < 0·05).
Variations in the sero-prevalence of antibody to brucella infection by cow, farm and area factors were investigated for three contrasting districts in Kenya: Samburu, an arid and pastoral area; Kiambu, a tropical highland area; and Kilifi, a typical tropical coastal area. Cattle were selected by a two-stage cluster sampling procedure and visited once between August 1991 and 1992.
Schall's algorithm, a statistical model suitable for multi-level analysis was used. Using this model, older age, free grazing and large herd size ([ges ] 31) were associated with higher seroprevalence. Also, significant farm-to-farm, area-to-area and district-to-district variations were estimated. The patterns of high risk districts and areas seen were consistent with known animal husbandry and movement risk factors, but the larger than expected farm-to-farm variation within high risk areas and districts could not be explained. Thus, a multi-level method provided additional information beyond conventional analyses of sero-prevalence data.
A dairy herd associated with Escherichia coli O157 infection in humans was studied for the 15 months following the outbreak to examine seasonal, age and management factors affecting faecal excretion of the organism and to determine the mode and frequency of milk contamination with the organism. Between May 1993 and July 1994, 28 visits were made to the farm to collect a total of 3593 rectal swabs from cows, heifers and calves and 329 milk samples. E.coli O157:H7 was isolated from 153 (4·3%) of 3593 bovine rectal swabs. The maximum prevalence at any one visit was 14% in lactating cows, 40% in non-lactating cows, 56% in calves and 68% in heifers. The prevalence in lactating cows, which was significantly lower than in the other groups, peaked during May–July 1993 and again briefly after the cattle were housed during November 1993 and then again during May 1994. Excretion rates of E. coli O157:H7 in lactating cows were highest during the first month after calving, falling during lactation and rising to another peak at 7 months postpartum. Between November 1993 and May 1994 there was no evidence of excretion in any group. Eighty-seven (74%) of the animals which excreted E. coli O157:H7 did so on only one occasion but 23 (32%) of 73 cows and heifers and 7 (16%) of 44 calves which excreted the organism did so on more than one occasion. E. coli O157:H7 was not isolated from milk taken from the bulk tank but it was isolated from individual milk samples (one milk jar and one fore-milk) from two animals previously shown to be faecal excretors of the organism. All isolates of E. coli O157:H7 obtained were of the same phage type, toxin genotype and plasmid profile.
In order to evaluate prophylaxis and therapy for individuals infected with pathogens by the airborne route, we have designed and built a simple apparatus in which small laboratory animals may be exposed to aerosols of infectious microorganisms. Animals are kept in a chamber closed by a HEPA filter and exposed to the pathogen aerosolized using a Collison nebulizer. Air in the exposure chamber may be sampled to show that the infectious agent is present but the dose of agent must be expressed as 50% effective doses determined by titration. An effective dose may be defined by whatever criteria are chosen to judge disease. Using this apparatus we have shown that St Louis encephalitis (SLE) virus is infectious for mice by the airborne route. These data support the idea that there may be significant hazard to personnel exposed to aerosols of infectious SLE after a laboratory accident.
Viruses from the recent epidemic of swine vesicular disease (SVD) in Europe have been isolated and characterized by antigenic and genetic methods to examine the likely epidemiological origins of the disease. Antigenic analysis was performed on 77 SVD viruses (SVDV) isolated in Europe between 1966 and 1994 using two panels of monoclonal antibodies (MAb) in a trapping ELISA. Genetic analysis of 33 of the SVD viruses by reverse transcription-polymerase chain-reaction (RT-PCR) amplification and nucleotide sequencing of the 1D (VP1) coding region was also performed. Comparison of the nucleotide sequences with each other and with three other previously published SVDV sequences revealed four distinct groups which correlated exactly with the results of the pattern of reactivity with MAbs. The first group consisted solely of the earliest SVD virus isolated (ITL/1/66) while the second group comprised viruses present in Europe and Japan between 1972 and 1981. The third group consisted of viruses isolated from outbreaks of SVD in Italy between December 1988 and June 1992. Viruses isolated between 1987 and 1994 from Romania, the Netherlands, Italy and Spain formed a fourth group. The genetic and antigenic similarity of the most recent virus isolates from Western Europe to a virus isolated in Romania 5 years previously suggests that the possible origin of the recent epidemic of swine vesicular disease in Western Europe was in Eastern Europe.
The prevalence of African horse sickness (AHS) serotypes in zebra foals from the Kruger National Park, South Africa was examined for possible associations between serotypes and to estimate the basic reproduction number, R0. The distributions of serotypes between zebra were not independent in the 6- and 7–8-month-old age classes (P < 0·005). This does not necessarily imply biological interactions between serotypes, as heterogeneity in host-vector transmission rates can generate non-independent distributions of serotypes. Both age and month of capture were significant factors in the number of serotypes infecting each zebra (P < 0·0001). Pairwise, positive associations between non-cross-reacting serotypes were found in the 7–8-month-old class only. For AHS overall, estimates of R0 ranged from 31–68. Assuming serotypes are transmitted independently, estimates of R0 for individual serotypes ranged from 10 for serotype 1 to 23 for serotype 6. The wide range of estimates emphasizes the need for a better understanding of serotype transmission and interactions in AHS.
The effectiveness of influenza vaccine in reducing hospital admissions for pneumonia, influenza, bronchitis, or emphysema was assessed by a case-control study of people aged 16 years and older who were admitted to 10 Leicestershire hospitals between 1 December 1989 and 31 January 1990. Hospital and general practitioners' records for 156 admissions (the cases) and 289 controls matched for age and sex were reviewed. Information was collected on demography, the usual place of residence (institutional or non-institutional), the existence of chronic illness, and vaccination during the 5 years before admission. The odds ratio for hospital admission among vaccinees was 0·67 (95% CI 0·39–1·12) giving an estimate of vaccine effectiveness in this setting of 33% (95% CI 0–61). However, multivariate logistic regression, adjusting for the effects of institutional care and chronic illness, revealed that influenza vaccination reduced hospital admissions by 63% (95% CI 17–84%). There was a strong trend towards improved vaccine effectiveness when used in institutional settings. Influenza vaccine is effective in reducing hospital admissions for influenza, pneumonia, bronchitis and emphysema, and effectiveness is comparable to that observed for influenza and pneumonia admissions in North America.
We propose a novel model for the interaction between HIV and the immune system. Two differential equations describe the interactions between one strain of virus and one clone of T-lymphocytes. We employ the model to generalize earlier results on the AIDS diversity threshold (Nowak et al. 1990, Nowak et al. 1991). Virus diversity is implemented in the model by assuming that all virus strains and all T-cell clones are identical. Given this assumption, diversity is represented as a parameter.
First we confirm the earlier results by showing that our model has a diversity threshold corresponding to a saddle-node bifurcation. We derive an analytical expression for the local bifurcation point in terms of the parameters. This shows that the diversity threshold corresponds to a linear combination of the diversity, infectivity, and antigenicity of the virus quasi-species. The mechanism by which an increase in diversity causes AIDS is by increasing the total virus concentration.
Secondly we derive a ‘virulence’ threshold corresponding to a global bifurcation involving the basins of attraction. Here ‘virulence’ is defined as the infectivity and antigenicity of a virus strain. We derive an analytical expression for the global bifurcation point in terms of the parameters. A numerical study of the relation between the diversity and virulence thresholds suggests that the condition for the development of AIDS is a linear combination of diversity and virulence.
Acquired immunity is a particular type of density-dependent process that may affect the establishment, mortality or fecundity of parasitic helminths, as functions both of current infection and of past infection; that is, a densitydependent process with ‘memory’. This type of process is likely to have complicated impacts on parasite population dynamics because of this memory component (Woolhouse 1992a). The epidemiological impact of acquired immunity will also depend on which parasite life-cycle stage provides the antigen stimulating a protective response and on which stage is the target of the response. For human schistosomes (the main example used here), the relevant life cycle stages are larvae (cercariae and schistosomulae) (L), adult worms (A), and eggs (E). The evidence for different forms of immunity to schistosomes has been elegantly reviewed in Hagan and Wilkins (1993); possible combinations of target and response are: larval antigen/anti-larval response (an LL process); adult antigen/anti-larval response (an AL process); and adult antigen/antiadult response (an AA process).
Mathematical models
The models used here are described in detail elsewhere (Woolhouse 1992b, 1993, 1994) and are based on earlier elaborations of a simple immigrationdeath process (Anderson and May 1985, Roberts and Grenfell 1991). The models describe the dynamics of the worm burden, experience of infection, and level of resistance for a set of individuals in a population. Worm burden is self explanatory. Experience of infection corresponds to the (discounted) cumulative exposure to parasite antigens and can be interpreted as related to the numbers of specific memory cells.
Models of the transmission dynamics of sexually acquired infections have recently turned greater attention to the importance of sexual mixing patterns and sexual networks in the spread of such diseases (Hethcote and Yorke 1984, Ramstedt et al. 1992, Haraldsdottir et al. 1992). Apart from the theoretical problems of constructing models which can adequately characterise the complexity of human sexual partnership formation, there remain practical problems in obtaining sufficiently robust empirical data to measure parameters of interest for use by modellers. This paper addresses some aspects of empirical measurement and discusses the validity of some basic parameter estimates commonly used in models of sexually transmitted disease (STD) transmission, particularly where they are used to demonstrate quantitative rather than qualitative considerations.
Key parameters of interest in deterministic models include the population ‘rate of partner change’ and its variance, the probability of transmission per sexual partnership (or per act of intercourse) and the duration of infectiousness of the organism under consideration (Hethcote and Yorke 1984, Anderson and May 1988).
Recent studies of sexual behaviour (Johnson et al. 1992, ACSF investigators 1992, Catania et al 1992, MMWR. 1988) have emphasised the marked heterogeneity in sexual behaviour in human communities as measured by numbers of sexual partners in different time intervals. These distributions suggest that models need to take account not only of simple population means, but also to consider stratification of the population into high- and low-activity classes (Hethcote and Yorke 1984). This can, in part, be achieved by considering the demographic correlates of variability in sexual behaviour. These include, for example, varying effects in different cultures of age cohort, lifecourse, gender, marital and socio-economic status (Johnson et al. 1992).
This paper is concerned with evaluation of vaccination programs for viral diseases such as measles, mumps, rubella and hepatitis A. For such diseases an individual starts off susceptible, at some stage catches the disease and after a short infectious period becomes permanently immune. Vaccines for measles, mumps and rubella are currently in use and vaccines for hepatitis A are not yet widely available but are currently undergoing testing. The aim of this paper is to look at the evaluation of vaccination programs and their sensitivity to different mixing assumptions.
Mathematical models which accurately describe the spread of a disease must take into account the age-structure of the population amongst whom the disease is spreading. Anderson and May (1985) describe an age-structured mathematical model using partial differential equations, which is the basis of the one which we shall use. Age-structured data for these diseases is available in the form of case reports, or more reliably age-serological profiles. Anderson and May divide the population into discrete age classes and use computer simulation methods to evaluate different vaccination programs for measles, mumps and rubella.
Method
The force of infection at time t, λ(a, t), is defined as the probability per unit time that a susceptible individual of age a will become infected. We follow Keiding's non-parametric maximum likelihood method to estimate the force of infection assuming that the disease has settled down to its longterm equilibrium value. We use age-structured serological profiles for hepatitis A in Bulgaria given by Keiding (1991).
Individuals who are infected with the HIV virus, may or may not have had a positive HIV antibody test. From a public health point of view it is important to know the rate at which infected individuals have their infection diagnosed, that is, when they have their first positive antibody test. We will call this the rate of HIV diagnosis. Only HIV diagnosis prior to one year before AIDS diagnosis will be considered, since HIV tests close to AIDS diagnosis may possibly be closely linked to disease development.
One approach to estimating the rate of HIV diagnosis, is through information on the time of first HIV-diagnosis among individuals who develop AIDS. Such information has been made available for England and Wales by the Public Health Laboratory Service (PHLS) AIDS Centre at the Communicable Disease Surveillance Centre. For the period 1981–91, data are available on the number of AIDS cases diagnosed in each quarter, and reported by mid 1992, and, furthermore, on the number who had an earlier HIV-diagnosis, and on the quarter of this diagnosis.
We have defined an extended backcalculation method to incorporate the HIV diagnosis information. Three exposure groups are considered: homo/ bisexuals, injecting drug users, heterosexuals. For the first two groups the infection curve is assumed to have a quadratic exponential form up to a specified time (the knot) and constant thereafter; the knot has been taken at the beginning of 1987 and 1988 respectively. For the heterosexuals a quadratic exponential infection curve has been used.
A Weibull incubation period is assumed for the homo/bisexuals and heterosexuals, and a gamma incubation period for the injecting drug users.
This paper shows that the time trend of HIV infections among gay men could be forecast from persuasive information in the press. The principal methodologies are detailed in Fan (1993). The mainstream press was likely to be a good gauge of the persuasive information acting on the public for AIDS related topics because the news media could be used to forecast time trends of public opinion and behavior for over a dozen topics (e.g. Fan 1988, Fan and McAvoy 1989, Fan 1993). The analysis began with the electronic retrieval from the NEXIS commercial database of the texts of 2462 out of 8728 AIDS stories in the New York Times and the Washington Post from January 1, 1981 to February 12, 1992. The chosen stories contained the word ‘AIDS’ within five words of one of the word roots ‘disease’, ‘illness’ or ‘immune’. The 8.0 million characters of retrieved text were scored by computer using the Info Trend computer programs previously described (Fan 1988). The algorithm depended on the occurrence of key words, their orders in paragraphs and the distances between them. For the scoring, the analyst enters a topic specific dictionary and a set of word relationship rules, usually about 50 in number. The resulting scores are in the form of numbers of paragraphs containing user specified ideas at specific times.
The computer first discarded all paragraphs except those containing the word AIDS' or the word pair ‘acquired immune’. Then, the AIDS paragraphs were scored by machine for their views on HIV transmission through: sex, blood, nonsterile needles, the mother, casual contact, not through casual contact, and miscellaneous including mosquitos.