High and variable mortality of leatherback turtles reveal possible anthropogenic impacts.

The number of nesting leatherback turtles (Dermochelys coriacea) in the eastern Pacific Ocean has declined dramatically since the late 1980s. This decline has been attributed to egg poaching and interactions with fisheries. However, it is not clear how much of the decline should also be ascribed to variability in the physical characteristics of the ocean. We used data on individually marked turtles that nest at Playa Grande, Costa Rica, to address whether climatic variability affects survival and inter-breeding interval. Because some turtles might nest undetected, we used capture-recapture models to model survival probability accounting for a detection failure. In addition, as the probability of reproduction is constrained by past nesting events, we formulated a new parameterization to estimate inter-breeding intervals and contrast hypotheses on the role of climatic covariates on reproductive frequency. Average annual survival for the period 1993-2011 was low (0.78) and varied over time ranging from 0.49 to 0.99 with a negative temporal trend mainly due to the high mortality values registered after 2004. Survival probability was not associated with the Multivariate ENSO Index of the South Pacific Ocean (MEI) but this index explained 24% of the temporal variability in the reproductive frequency. The probability of a turtle to permanently leave after the first encounter was 26%. This high proportion of transients might be associated with a high mortality cost of the first reproduction or with a long-distance nesting dispersal after the first nesting season. Although current data do not allow separating these two hypotheses, low encounter rate at other locations and high investment in reproduction, supports the first hypothesis. The low and variable annual survival probability has largely contributed to the decline of this leatherback population. The lack of correlation between survival probability and the most important climatic driver of oceanic processes in the Pacific discards a climate-related decline and point to anthropogenic sources of mortality as the main causes responsible for the observed population decline.

Excess risk of hip fractures attributable to the use of antidepressants in five European countries and the USA.

SUMMARY: The association between antidepressant use and hip fracture remains unclear. We conducted a systematic review to estimate Population Attributable Risks (PAR) for France, Germany, Italy, Spain, UK, and the USA. We report a heterogeneous prevalence of antidepressant use and related PARs, both lowest for Italy and highest for the USA. INTRODUCTION: Antidepressant use has been associated with an increased hip fracture risk in observational studies. However, the potential contribution of antidepressant consumption on the population rate of hip fractures has not been described. Our aim was to estimate the impact of the use of different classes of antidepressants on the rate of hip fracture at a population-level in France, Germany, Italy, Spain, the UK, and the USA. METHODS: We conducted a systematic literature review to estimate the pooled relative risk (RR) of hip fracture according to use of antidepressants. Prevalence rates of antidepressant use (Pe) in 2009 were calculated for each country using the The Intercontinental Medical Statistics database and three public databases from Denmark, the Netherlands, and Norway. Both the RR and Pe were used to calculate PAR of hip fractures associated with antidepressant use. RESULTS: The literature review showed an increased risk of hip fractures in antidepressant users (RR, 1.7; 95 % confidence interval (CI), 1.5-2.0). Rates of antidepressant use showed considerable differences between countries, ranging from 4.4 % (Italy) to 11.2 % (USA) in the year 2009. The estimated PAR of antidepressants on hip fracture rates were 3.0 % (95 % CI, 2.0-4.1; Italy), 3.1 % (95 % CI, 2.1-4.3; Germany), 3.8 % (95 % CI, 2.6-5.3; France), 4.8 % (95 % CI, 3.3-6.5; Spain), 4.9 % (95 % CI, 3.4-6.8; UK), and 7.2 % (95 % CI, 5.0-9.9; USA). PARs differed for different types of antidepressants, with highest attributable risks for selective serotonin reuptake inhibitors. CONCLUSIONS: These findings suggest that the potential contribution of antidepressant use to the population rate of hip fractures in the five large EU countries and the USA varies between 3 and 7 %.

Potential impact of benzodiazepine use on the rate of hip fractures in five large European countries and the United States.

Benzodiazepine use increases the risk of falls and has been associated with an increased risk of hip fractures. Our aim was to estimate the possible population impact of the use of benzodiazepines on the rate of hip fracture in France, Germany, Italy, Spain, the United Kingdom, and the United States. We conducted a literature review to estimate the pooled relative risk (RR) for hip fractures and use of benzodiazepines. Prevalence rates of benzodiazepine use in 2009 were calculated for each country using the IMS MIDAS database and three public databases in Denmark, the Netherlands, and Norway. Both the RR and prevalence rates were used for calculation of population attributable risks (PARs) of hip fractures associated with benzodiazepine use. The literature review showed an increased risk of hip fractures in benzodiazepine users (RR = 1.4, 95 % CI 1.2-1.6). Rate of benzodiazepine use showed considerable differences between countries, ranging from 4.7 % to 22.3 % of population ever in a 1-year period. These are reflected in results for the PARs; estimated attributions of benzodiazepines to the rate of hip fractures were 1.8 %, 95 % CI 1.1-2.6 (Germany); 2.0 %, 95 % CI 1.2-2.8 (United Kingdom); 5.2 %, 95 % CI 3.2-7.3 (Italy); 7.4 %, 95 % CI 4.5-10.0 (France); 8.0 %, 95 % CI 4.9-11.0 (United States); and 8.2 %, 95 % CI 5.1-12.0 (Spain). PAR estimates suggest that the potential attribution of benzodiazepine use on the population rate of hip fractures in the five specified European countries and the United States varies between 1.8 % and 8.2 %. During the next phase of the IMI-PROTECT study, a comparison with individual patient data will show whether this approach is valid.

A randomised placebo-controlled trial to explore the effect of suppressive therapy with acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 among Zimbabwean sex workers.

OBJECTIVES: To determine the effect of daily acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 (HSV-2) in a randomised placebo-controlled trial among rural Zimbabwean sex workers. METHODS: 214 women were recruited and tested for HIV-1 and HSV-2 antibodies, HIV plasma viral load, CD4 lymphocyte count and genital swabs for qualitative detection of HIV-1 and HSV-2 genital shedding. Women were randomly assigned to acyclovir 400 mg twice a day for 12 weeks or matching placebo and were followed weekly to detect HIV-1 or HSV-2 genital shedding. Shedding analyses were only undertaken on 125 women co-infected with HSV-2 and HIV-1. Data were analysed using logistic regression, with random effects modelling used to account for repeated measurements on the same women. RESULTS: All women were randomly assigned to acyclovir or placebo; 125 of whom were co-infected with HIV-1 and HSV-2. 69 women were randomly assigned to acyclovir and 56 to placebo. Although twice daily acyclovir reduced rates of HSV-2 genital shedding, (adjusted odds ratio (AOR) 0.24; 95% CI 0.12 to 0.48; less than p<0.001), it had no effect on the proportion of visits at which HIV-1 shedding was detected (AOR 1.08; 95% CI 0.48 to 2.42; p = 0.9). Adherence varied between participants but even when adherence was high (as determined by pill count and extent of HSV-2 suppression) HIV-1 shedding was not reduced. CONCLUSION: Among these HIV-1 and HSV-2-seropositive women, suppressive acyclovir therapy had no effect on the rate of HIV genital shedding despite a reduction in genital HSV-2. Treatment adherence and its measurement clearly affect the interpretation of these results.

Measuring the success of canine and feline preventative healthcare consultations: A systematic review.

Preventative healthcare consultations account for a large proportion of the veterinary caseload. This novel study is the first to methodically review all literature on canine and feline preventative healthcare consultations. Previous research has found these consultations to be different from health problem consultations in terms of communication style and content. Identifying relevant evidence and previously validated methods of measuring the success of these consultations will be useful when implementing strategies for optimisation. The aim of this study was to identify and assess the quality of existing literature which describes and/or measures the success of preventative healthcare consultations. Database searches of CAB Abstracts and Medline were conducted to identify published literature. Google searches were then conducted to identify any additional published or grey literature. Results were systematically screened to determine whether the returned sources were about cats and/or dogs, whether they related to preventative healthcare, and whether they described and/or measured the success of preventative healthcare consultations. For primary research citations which only described preventative healthcare consultations, data were extracted on the aspects of the consultations described. For citations which additionally measured the success of the consultations, the measures used, sampling technique, key results and key weaknesses were also extracted. Of 17,538 citations identified in total during the database searches, a total of seven relevant primary research citations were identified. All of these citations described aspects of the preventative healthcare consultation, such as consultation length, health problems discussed, actions taken and communication style. Only one primary research citation measured success of the consultation, using veterinarian satisfaction to determine success. In addition, 30 narrative citations, including expert opinion pieces, textbooks, guidelines without transparent methodology and conference presentations were identified. Google searches identified 224 relevant narrative citations, and five of the seven primary research citations identified by the database searches, but did not identify any additional relevant primary research citations. The results suggest that, despite accounting for around a third of all consultations, there is relatively little evidence describing preventative healthcare consultations and only one measure of success has been described for these consultations. This presents potential challenges when implementing strategies to optimise these consultations, as measures which are useful and relevant to veterinary practice should first be identified. Identifying useful measures of success will allow future strategies designed to maximise the benefits of these consultations to be meaningfully assessed for efficacy.

Common decisions made and actions taken during small-animal consultations at eight first-opinion practices in the United Kingdom.

In order for veterinary surgeons to undertake an evidence-based approach to making decisions about their patients, it is important that new evidence is generated to support the clinical decision-making process. Many of the decisions are likely to be around the actions taken to treat or manage health problems discussed during the consultation, and little is currently known about the factors which affect the type of action taken. The aim of this study was to determine the decisions made and actions taken for health problems discussed during first-opinion small-animal consultations, as well as identifying factors which may affect the decision-making process. Data were gathered during direct observation of small-animal consultations conducted by 62 veterinary surgeons in eight first-opinion practices in the United Kingdom. For each patient presented, data were gathered on all health problems discussed during the consultation. The decision made (whether an action was taken or not) and the action taken where applicable (e.g. therapeutic treatment with antibiotics) was also recorded. A three-level multivariable logistic-regression model was developed, with problem (Level 1) nested within patient (Level 2) nested within consulting veterinary surgeon (Level 3), and a binary outcome variable of action versus no action. At least one action was taken for 69% (n=2203/3192) of all problems discussed. Therapeutic treatment was the most common action taken (n=1286/3192 problems; 40.3%), followed by management advice (n=1040/3192; 32.6%) and diagnostic work-up (n=323/3192; 10.1%). The most common therapeutic treatment was antibiotics (n=386/1286; 30%), while the most common management advice given was dietary advice (n=509/1040; 48.9%). The three explanatory variables remaining in the final model were whether the problem was a presenting or non-presenting problem, the type of diagnosis made, and the body system affected. Explanatory variables which did not remain in the final model were patient signalment, problem history, consultation type, clinical examination type, and who raised the problem (veterinary surgeon or owner). For over two-thirds of problems discussed, an action was taken which suggests these problems may be seen as important by the veterinary surgeon and/or pet owner. No action was taken for almost a third of cases which could represent 'watchful waiting', which has been highlighted as important in human healthcare. Future research should focus on the common actions taken, further exploring the complex decision-making process, and examining the effect of the decisions made on long-term patient outcomes.

Investigating preventive-medicine consultations in first-opinion small-animal practice in the United Kingdom using direct observation.

Preventive-medicine consultations account for a large proportion of the veterinary caseload and previous research has suggested these consultations are fundamentally different from those in which the animal is presented for a specific health problem. There has been recent controversy around some aspects of preventive medicine for cats and dogs, and the full health benefits of the preventive-medicine consultation remain unclear. The aim of this study was to compare characteristics of the consultation and the problems discussed during the consultation between preventive-medicine consultations and other types of consultations. Data were gathered during direct observation of small-animal consultations in seven first-opinion practices in the United Kingdom. Data collected included type of clinical examination performed, patient signalment, and details of all problems discussed (including whether the problem was presenting or non-presenting, new or pre-existing, who had raised the problem, body system affected and whether an action was taken). A two-level multivariable logistic-regression model was developed, with canine and feline patients at Level 1 nested within consulting veterinary surgeons at Level 2, and a binary outcome variable of preventive-medicine consultation versus specific health-problem consultation. A total of 1807 patients were presented, of which 690 (38.2%) presented for a preventive-medicine consultation. Dogs were the most frequently presented species (n=1168; 64.6%) followed by cats (n=510; 28.2%), rabbits (n=86; 4.8%) and patients of other species (n=43; 2.4%). The five variables remaining in the multi-level model were whether multiple patients were presented, patient age, clinical examination type, weighing and number of problems discussed. Species, breed, sex, neutering status and practice did not remain in the final model. Many non-presenting problems, including both preventive-medicine problems and specific-health problems, were discussed and acted upon during all types of consultations. Dental and behavioural non-presenting problems were discussed more frequently during preventive-medicine consultations compared with specific health-problem consultations. Preventive-medicine consultations represent an opportunity for veterinary surgeons to discuss other aspects of preventive medicine, and to detect and manage new and ongoing health problems. A greater evidence base is needed to understand whether detecting and managing underlying disease during the preventive-medicine consultation has a positive impact on lifelong patient health and welfare.

Factors influencing common diagnoses made during first-opinion small-animal consultations in the United Kingdom.

It is currently unclear how frequently a diagnosis is made during small-animal consultations or how much of a role making a diagnosis plays in veterinary decision-making. Understanding more about the diagnostic process will help direct future research towards areas relevant to practicing veterinary surgeons. The aim of this study was to determine the frequency with which a diagnosis was made, classify the types of diagnosis made (and the factors influencing these) and determine which specific diagnoses were made for health problems discussed during small-animal consultations. Data were gathered during real-time direct observation of small-animal consultations in eight practices in the United Kingdom. Data collected included characteristics of the consultation (e.g. consultation type), patient (e.g. breed), and each problem discussed (e.g. new or pre-existing problem). Each problem discussed was classified into one of the following diagnosis types: definitive; working; presumed; open; previous. A three-level multivariable logistic-regression model was developed, with problem (Level 1) nested within patient (Level 2) nested within consulting veterinary surgeon (Level 3). Problems without a previous diagnosis, in cats and dogs only, were included in the model, which had a binary outcome variable of definitive diagnosis versus no definitive diagnosis. Data were recorded for 1901 animals presented, and data on diagnosis were gathered for 3192 health problems. Previous diagnoses were the most common diagnosis type (n=1116/3192; 35.0%), followed by open (n=868/3192; 27.2%) then definitive (n=660/3192; 20.7%). The variables remaining in the final model were patient age, problem history, consultation type, who raised the problem, and body system affected. New problems, problems in younger animals, and problems raised by the veterinary surgeon were more likely to result in a definitive diagnosis than pre-existing problems, problems in older animals, and problems raised by the owner. The most common diagnoses made were overweight/obese and periodontal disease (both n=210; 6.6%). Definitive diagnoses are rarely made during small-animal consultations, with much of the veterinary caseload involving management of ongoing problems or making decisions around new problems prior to a diagnosis being made. This needs to be taken into account when considering future research priorities, and it may be necessary to conduct research focused on the approach to common clinical presentations, rather than purely on the common diagnoses made. Examining how making a diagnosis affects the actions taken during the consultation may shed further light on the role of diagnosis in the clinical decision-making process.

Microbial metallothioneins.

Bacterial metallothioneins bind, sequester and buffer excess intracellular zinc. At present, the vast majority of the available experimental data relate to cyanobacterial metallothionein, SmtA, from Synechococcus PCC 7942. SmtA is required for normal resistance to zinc and smtA-mediated zinc resistance has been used as a selectable marker. The imidazole groups of histidine residues, in addition to the thiol groups of cysteine residues, co-ordinate zinc in bacterial metallothioneins. The structure of bacterial metallothionein must facilitate some discrimination between 'adventitious' and 'adventageous' zinc-binding sites such that under excess zinc conditions metal is predominantly scavenged from the former. It remains unclear whether or not bacterial metallothionein also acts as a zinc store that supplies zinc-requiring proteins or if under some conditions it deactivates a subset of proteins via zinc removal. Expression of smtA is induced in response to elevated concentrations of zinc via the action of SmtB. SmtB has some sequence similarity to the arsenic responsive repressor ArsR and genes encoding related proteins are present in many bacterial genomes. Metal perception by SmtB differs from ArsR. The latter contains a characteristic Cys-Val-Cys motif associated with a DNA-binding helix-turn-helix (the ArsR motif), while the former contains metal-binding motifs associated with a carboxyl-terminal alpha-helix that forms the interface between SmtB dimers (the SmtB motif). Some SmtB-ArsR family proteins, including the zinc sensor ZiaR from the cyanobacterium Synechocystis PCC 6803, have the metal-sensory motifs of both SmtB and ArsR. The mechanisms of action, and the features that allow discrimination between different metal ions by these sensors, are discussed.

Investigating common clinical presentations in first opinion small animal consultations using direct observation.

Understanding more about the clinical presentations encountered in veterinary practice is vital in directing research towards areas relevant to practitioners. The aim of this study was to describe all problems discussed during a convenience sample of consultations using a direct observation method. A data collection tool was used to gather data by direct observation during small animal consultations at eight sentinel practices. Data were recorded for all presenting and non-presenting specific health problems discussed. A total of 1901 patients were presented with 3206 specific health problems discussed. Clinical presentation varied widely between species and between presenting and non-presenting problems. Skin lump, vomiting and inappetence were the most common clinical signs reported by the owner while overweight/obese, dental tartar and skin lump were the most common clinical examination findings. Skin was the most frequently affected body system overall followed by non-specific problems then the gastrointestinal system. Consultations are complex, with a diverse range of different clinical presentations seen. Considering the presenting problem only may give an inaccurate view of the veterinary caseload, as some common problems are rarely the reason for presentation. Understanding the common diagnoses made is the next step and will help to further focus questions for future research.

Capturing the complexity of first opinion small animal consultations using direct observation.

Various different methods are currently being used to capture data from small animal consultations. The aim of this study was to develop a tool to record detailed data from consultations by direct observation. A second aim was to investigate the complexity of the consultation by examining the number of problems discussed per patient. A data collection tool was developed and used during direct observation of small animal consultations in eight practices. Data were recorded on consultation type, patient signalment and number of problems discussed. During 16 weeks of data collection, 1901 patients were presented. Up to eight problems were discussed for some patients; more problems were discussed during preventive medicine consultations than during first consultations (P<0.001) or revisits (P<0.001). Fewer problems were discussed for rabbits than cats (P<0.001) or dogs (P<0.001). Age was positively correlated with discussion of specific health problems and negatively correlated with discussion of preventive medicine. Consultations are complex with multiple problems frequently discussed, suggesting comorbidity may be common. Future research utilising practice data should consider how much of this complexity needs to be captured, and use appropriate methods accordingly. The findings here have implications for directing research and education as well as application in veterinary practice.

Modelling the impact of alternative HIV intervention strategies in rural Uganda.

OBJECTIVE: To assess the likely impact on HIV incidence of increased condom use, a reduction in casual sexual partners, treatment programmes for other sexually transmitted diseases (STD) and combinations of these in rural Uganda. METHODS: A simulation model for the transmission dynamics of HIV infection and STD was employed, drawing on data from a rural population cohort in South-West Uganda with an HIV prevalence of 9% among adults in 1990. RESULTS: For the scenario most consistent with data from the study population, 39% of all adult HIV infections were averted, in the 10 years from 1990, when condoms were used consistently and effectively by 50% of men in their contacts with one-off sexual partners (such as bar girls and commercial sex workers). Reducing by 50% the frequency of men's sexual contacts with one-off partners averted 68% of infections. Reducing by 50% the duration of all STD episodes averted 43% of infections. Combining these three interventions averted 82% of all adult infections in the 10 years from 1990. CONCLUSION: A substantial proportion of HIV infections may be averted in general populations through interventions targeted only on less regular sexual partnerships.

PIP: Simulation modelling was used to improve understanding of the transmission of human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs) in rural Uganda and assess the effectiveness of various preventive interventions. Each individual in the simulated population was represented by a set of characteristics (e.g., age, sex, HIV and STD status, type of sexual relationship, identity of all sexual partners) existent in a rural population cohort in South West Uganda in 1990 with an adult HIV prevalence rate of 9%. HIV transmission per sexual contact was assumed to be enhanced 10-fold (low co-factor scenario) or 100-fold (high co-factor scenario) during episodes of ulcerative STD. Even under the high co-factor conditions, 50% condom use resulted in a 39% reduction in HIV over 10 years. A 50% reduction in the frequency of sexual contacts with one-off partners (e.g., prostitutes) averted 68% of infections. When the duration of all STD episodes was reduced by 50%, 43% of infections were averted by the year 2000. If all three of these interventions were combined, 82% of HIV incidence was averted by the year 2000. These findings suggest that a substantial proportion of HIV disease can be prevented through interventions that target only casual sexual partners.

The epidemiology of gonorrhoea, chlamydial infection and syphilis in four African cities.

OBJECTIVES: To compare the epidemiology of gonorrhoea, chlamydial infection and syphilis in four cities in sub-Saharan Africa; two with a high prevalence of HIV infection (Kisumu, Kenya and Ndola, Zambia), and two with a relatively low HIV prevalence (Cotonou, Benin and Yaoundé, Cameroon). DESIGN: Cross-sectional study, using standardized methods, including a standardized questionnaire and standardized laboratory tests, in four cities in sub-Saharan Africa. METHODS: In each city, a random sample of about 2000 adults aged 15-49 years was taken. Consenting men and women were interviewed about their socio-demographic characteristics and their sexual behaviour, and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection, and (women only) Trichomonas vaginalis infection. Risk factor analyses were carried out for chlamydial infection and syphilis seroreactivity. RESULTS: The prevalence of gonorrhoea ranged between 0% in men in Kisumu and 2.7% in women in Yaoundé. Men and women in Yaoundé had the highest prevalence of chlamydial infection (5.9 and 9.4%, respectively). In the other cities, the prevalence of chlamydial infection ranged between 1.3% in women in Cotonou and 4.5% in women in Kisumu. In Ndola, the prevalence of syphilis seroreactivity was over 10% in both men and women; it was around 6% in Yaoundé, 3-4% in Kisumu, and 1-2% in Cotonou. Chlamydial infection was associated with rate of partner change for both men and women, and with young age for women. At the population level, the prevalence of chlamydial infection correlated well with reported rates of partner change. Positive syphilis serology was associated with rate of partner change and with HSV-2 infection. The latter association could be due to biological interaction between syphilis and HSV-2 or to residual confounding by sexual behaviour. At the population level, there was no correlation between prevalence of syphilis seroreactivity and reported rates of partner change. CONCLUSION: Differences in prevalence of chlamydial infection could be explained by differences in reported sexual behaviour, but the variations in prevalence of syphilis seroreactivity remained unexplained. More research is needed to better understand the epidemiology of sexually transmitted infections in Africa.

The epidemiology of trichomoniasis in women in four African cities.

OBJECTIVES: To describe the epidemiology of Trichomonas vaginalis infection and its association with HIV infection, in women in four African cities with different levels of HIV infection. DESIGN: Cross-sectional study, using standardized methods, including a standardized questionnaire and standardized laboratory tests, in four cities in sub-Saharan Africa: two with a high prevalence of HIV infection (Kisumu, Kenya and Ndola, Zambia), and two with a relatively low prevalence of HIV (Cotonou, Benin and Yaoundé, Cameroon). METHODS: In each city, a random sample of about 2000 adults aged 15-49 years was taken. Consenting men and women were interviewed about their socio-demographic characteristics and their sexual behaviour, and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection, and (women only) T. vaginalis infection. Risk factor analyses were carried out for trichomoniasis for each city separately. Multivariate analysis, however, was only possible for Yaoundé, Kisumu and Ndola. RESULTS: The prevalence of trichomoniasis was significantly higher in the high HIV prevalence cities (29.3% in Kisumu and 34.3% in Ndola) than in Cotonou (3.2%) and Yaoundé (17.6%). Risk of trichomoniasis was increased in women who reported more lifetime sex partners. HIV infection was an independent risk factor for trichomonas infection in Yaoundé [adjusted odds ratio (OR) = 1.8, 95% confidence interval (CI) = 0.9-3.7] and Kisumu (adjusted OR = 1.7, 95% CI = 1.1-2.7), but not in Ndola. A striking finding was the high prevalence (40%) of trichomonas infection in women in Ndola who denied that they had ever had sex. CONCLUSION: Trichomoniasis may have played a role in the spread of HIV in sub-Saharan Africa and may be one of the factors explaining the differences in levels of HIV infection between different regions in Africa. The differences in prevalence of trichomoniasis between the four cities remain unexplained, but we lack data on the epidemiology of trichomoniasis in men. More research is required on the interaction between trichomoniasis and HIV infection, the epidemiology of trichomoniasis in men, and trichomonas infections in women who deny sexual activity.

Ecological and individual level analysis of risk factors for HIV infection in four urban populations in sub-Saharan Africa with different levels of HIV infection.

OBJECTIVE: To identify factors that could explain differences in rate of spread of HIV between different regions in sub-Saharan Africa. DESIGN: Cross-sectional study. METHODS: The study took place in two cities with a relatively low HIV prevalence (Cotonou, Benin and Yaoundé, Cameroon), and two cities with a high HIV prevalence (Kisumu, Kenya and Ndola, Zambia). In each of these cities, a representative sample was taken of about 1000 men and 1000 women aged 15-49 years. Consenting men and women were interviewed about their socio-demographic background and sexual behaviour; and were tested for HIV, herpes simplex virus type 2 (HSV-2), syphilis, Chlamydia trachomatis and Neisseria gonorrhoea infection, and (women only) Trichomonas vaginalis. Analysis of risk factors for HIV infection was carried out for each city and each sex separately. Adjusted odds ratios (aOR) were obtained by multivariate logistic regression. RESULTS: The prevalence of HIV infection in sexually active men was 3.9% in Cotonou, 4.4% in Yaoundé, 21.1% in Kisumu, and 25.4% in Ndola. For women, the corresponding figures were 4.0, 8.4, 31.6 and 35.1%. High-risk sexual behaviour was not more common in the high HIV prevalence cities than in the low HIV prevalence cities, but HSV-2 infection and lack of circumcision were consistently more prevalent in the high HIV prevalence cities than in the low HIV prevalence cities. In multivariate analysis, the association between HIV infection and sexual behavioural factors was variable across the four cities. Syphilis was associated with HIV infection in Ndola in men [aOR = 2.7, 95% confidence interval (CI) = 1.5-4.91 and in women (aOR = 1.7, 95% CI = 1.1-2.6). HSV-2 infection was strongly associated with HIV infection in all four cities and in both sexes (aOR ranging between 4.4 and 8.0). Circumcision had a strong protective effect against the acquisition of HIV by men in Kisumu (aOR = 0.25, 95% CI = 0.12-0.52). In Ndola, no association was found between circumcision and HIV infection but sample sizes were too small to fully adjust for confounding. CONCLUSION: The strong association between HIV and HSV-2 and male circumcision, and the distribution of the risk factors, led us to conclude that differences in efficiency of HIV transmission as mediated by biological factors outweigh differences in sexual behaviour in explaining the variation in rate of spread of HIV between the four cities.

The epidemiology of HSV-2 infection and its association with HIV infection in four urban African populations.

OBJECTIVES: To estimate age- and sex-specific herpes simplex virus type-2 (HSV-2) prevalence in urban African adult populations and to identify factors associated with infection. DESIGN AND METHODS: Cross-sectional, population-based samples of about 2000 adults interviewed in each of the following cities: Cotonou, Benin; Yaoundé, Cameroon; Kisumu, Kenya and Ndola, Zambia. Consenting study participants were tested for HIV, HSV-2 and other sexually transmitted infections. RESULTS: HSV-2 prevalence was over 50% among women and over 25% among men in Yaoundé, Kisumu and Ndola, with notably high rates of infection among young women in Kisumu and Ndola (39% and 23%, respectively, among women aged 15-19 years). The prevalence in Cotonou was lower (30% in women and 12% in men). Multivariate analysis showed that HSV-2 prevalence was significantly associated with older age, ever being married, and number of lifetime sexual partners, in almost all cities and both sexes. There was also a strong, consistent association with HIV infection. Among women, the adjusted odds ratios for the association between HSV-2 and HIV infections ranged from 4.0 [95% confidence interval (CI) = 2.0-8.0] in Kisumu to 5.5 (95% CI = 1.7-18) in Yaoundé, and those among men ranged from 4.6 (95% CI = 2.7-7.7) in Ndola to 7.9 (95% CI = 4.1-15) in Kisumu. CONCLUSIONS: HSV-2 infection is highly prevalent in these populations, even at young ages, and is strongly associated with HIV at an individual level. At a population level, HSV-2 prevalence was highest in Kisumu and Ndola, the cities with the highest HIV rates, although rates were also high among women in Yaoundé, where there are high rates of partner change but relatively little HIV infection. The high prevalence of both infections among young people underlines the need for education and counselling among adolescents.

Multicentre study on factors determining differences in rate of spread of HIV in sub-Saharan Africa: methods and prevalence of HIV infection.

OBJECTIVE: The objective of this study was to explore whether the differences in rate of spread of HIV in different regions in sub-Saharan Africa could be explained by differences in sexual behaviour and/or factors influencing the probability of HIV transmission during sexual intercourse. METHODS: A cross-sectional, population-based study was conducted in two cities with a high HIV prevalence (Kisumu in Kenya and Ndola in Zambia) and two cities with a relatively low HIV prevalence (Cotonou in Benin and Yaoundé in Cameroon). In each of these cities, approximately 1000 men and 1000 women, aged 15-49 years, were randomly selected from the general population. Consenting men and women were interviewed and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection and trichomoniasis (the latter for women only). In addition, a survey was conducted on a random sample of 300 sex workers in each city. The research instruments, including the questionnaires and the laboratory procedures, were standardized to permit comparison of results. RESULTS: The numbers of men interviewed were 1021 in Cotonou, 973 in Yaoundé, 829 in Kisumu, and 720 in Ndola. The corresponding figures for women were 1095, 1116, 1060 and 1130. In Yaoundé, Kisumu and Ndola, the response rates for men were lower than for women due to failure to make contact with eligible men. The proportion of eligible women who were interviewed was 86% in Yaoundé, and 89% in Kisumu and Ndola. In Yaoundé, 76% of eligible men were interviewed, along with 82% in Kisumu and 75% in Ndola. The prevalence of HIV infection in men was 3.3% in Cotonou, 4.1% in Yaoundé, 19.8% in Kisumu and 23.2% in Ndola. For women, the respective figures were 3.4, 7.8, 30.1 and 31.9%. The prevalence of HIV infection among women aged 15-19 years was 23.0% in Kisumu and 15.4% in Ndola. Among women in Kisumu who had their sexual debut 5 years before the interview, the prevalence of HIV infection was 46%; in Ndola, it was 59%. Among sex workers, the prevalence of HIV infection was 57.5% in Cotonou, 34.4% in Yaoundé, 74.7% in Kisumu and 68.7% in Ndola. CONCLUSIONS: The HIV prevalence rates in the general population confirmed our preliminary assessment of the level of HIV infection in the four cities, which was based on estimates of HIV prevalence from sentinel surveillance among pregnant women. The very high prevalence of HIV infection among young women in Kisumu and Ndola calls for urgent intervention.

Cyanobacterial metallothionein gene expressed in Escherichia coli. Metal-binding properties of the expressed protein.

The recently isolated Synechococcus gene smtA encodes the only characterised prokaryotic protein designated to be a metallothionein (MT). To examine the metal-binding properties of its product the smtA gene was expressed in Escherichia coli as a carboxyterminal extension of glutathione-S-transferase. The pH of half dissociation of Zn, Cd and Cu ions from the expressed protein was determined to be 4.10, 3.50, 2.35, respectively, indicating a high affinity for these ions (in particular for Zn in comparison to mammalian MT). E. coli expressing this gene showed enhanced (ca. 3-fold) accumulation of Zn.

A gene from pea (Pisum sativum L.) with homology to metallothionein genes.

While searching for 'organ-specific' genes in pea (Pisum sativum L.) we have isolated a gene (designated PsMTA) which has an ORF encoding a predicted protein with some similarity to metallothioneins (MTs). The PsMTA transcript is abundant in roots which have not been exposed to elevated concentrations of trace metals.