Tuberculosis screening of migrants to low-burden nations: insights from evaluation of UK practice.

Tuberculosis (TB) primarily occurs in the foreign-born in European countries, such as the UK, where increasing notifications and the high proportion of foreign-born cases has refocused attention on immigrant (new entrant) screening. We investigated how UK primary care organisations (PCOs) screen new entrants and whether this differs according to TB burden in the PCOs (incidence < 20 or ≥ 20 cases per 100,000 per annum). An anonymous, 20-point questionnaire was sent to all 192 UK PCOs asking which new entrants are screened, who is screened for active TB/latent TB infection (LTBI) and the methods used. Descriptive analyses were undertaken. Categorical responses were compared using the Chi-squared test. 177 (92.2%) out of 192 PCOs responded; all undertook screening action in response to abnormal chest radiographs, but only 107 (60.4%) screened new entrants for LTBI. Few new entrants had active TB diagnosed (median 0.0%, interquartile range (IQR) 0.0-0.5%) but more were identified with LTBI (median 7.85%, IQR 4.30-13.50%). High-burden PCOs were significantly less likely to screen new entrants for LTBI (OR 0.26, 95% CI 0.12-0.54; p<0.0001). Among PCOs screening for LTBI, there was substantial deviation from national guidance in selection of new entrant subgroups and screening method. Considerable heterogeneity and deviation from national guidance exist throughout the UK new entrant screening process, with high-burden regions undertaking the least screening. Forming an accurate picture of current front-line practice will help to inform future development of European new entrant screening policy.

Estimating the resources required in the roll-out of universal access to antiretroviral treatment in Zimbabwe.

OBJECTIVES: To develop projections of the resources required (person-years of drug supply and healthcare worker time) for universal access to antiretroviral treatment (ART) in Zimbabwe. METHODS: A stochastic mathematical model of disease progression, diagnosis, clinical monitoring and survival in HIV infected individuals. FINDINGS: The number of patients receiving ART is determined by many factors, including the strategy of the ART programme (method of initiation, frequency of patient monitoring, ability to include patients diagnosed before ART became available), other healthcare services (referral rates from antenatal clinics, uptake of HIV testing), demographic and epidemiological conditions (past and future trends in incidence rates and population growth) as well as the medical impact of ART (average survival and the relationship with CD4 count when initiated). The variations in these factors lead to substantial differences in long-term projections; with universal access by 2010 and no further prevention interventions, between 370 000 and almost 2 million patients could be receiving treatment in 2030-a fivefold difference. Under universal access, by 2010 each doctor will initiate ART for up to two patients every day and the case-load for nurses will at least triple as more patients enter care and start treatment. CONCLUSIONS: The resources required by ART programmes are great and depend on the healthcare systems and the demographic/epidemiological context. This leads to considerable uncertainty in long-term projections and large variation in the resources required in different countries and over time. Understanding how current practices relate to future resource requirements can help optimise ART programmes and inform long-term public health planning.

Men who have sex with men and women in Bangalore, South India, and potential impact on the HIV epidemic.

OBJECTIVE: The aim of this study was to quantify differences in patterns of sexual behaviour among men who have sex with men and women (MSMW) compared with men who have sex with men only (MSMO), and to examine the extent to which bisexual behaviour may act as a bridge for introducing HIV infection into the general population. METHODS: A cross-sectional survey in Bangalore city in 2006, which sampled men seeking sex with men in public places and hammams (bath houses where transgender individuals sell sex to men). RESULTS: Among a sample of 357 men reporting same-sex behaviour; 41% also reported sex with a woman in the past year and 14% were currently married to a woman, only two of whom had informed their wives about having sex with men. Condom use was very inconsistent with all male partners, while 98% reported unprotected vaginal sex with their wives. MSMW reported lower rates of risky behaviour with other men than MSMO: fewer reported selling sex (17% vs 58%), or receptive anal sex with known (28% vs 70%) or unknown (30% vs 59%) non-commercial partners. CONCLUSION: Bisexual behaviour was common among men seeking sex with men sampled in this survey. Although MSMW reported lower rates of risky sexual behaviour with male partners than MSMO, inconsistent condom use with both male and female partners indicates a potential means of HIV transmission into the general population. HIV prevention programmes and services should reach bisexual men who potentially expose their male and female partners to HIV.

Measuring trends in age at first sex and age at marriage in Manicaland, Zimbabwe.

OBJECTIVE: To identify reporting biases and to determine the influence of inconsistent reporting on observed trends in the timing of age at first sex and age at marriage. METHODS: Longitudinal data from three rounds of a population-based cohort in eastern Zimbabwe were analysed. Reports of age at first sex and age at marriage from 6837 individuals attending multiple rounds were classified according to consistency. Survival analysis was used to identify trends in the timing of first sex and marriage. RESULTS: In this population, women initiate sex and enter marriage at younger ages than men but spend much less time between first sex and marriage. Among those surveyed between 1998 and 2005, median ages at first sex and first marriage were 18.5 years and 21.4 years for men and 18.2 years and 18.5 years, respectively, for women aged 15-54 years. High levels of reports of both age at first sex and age at marriage among those attending multiple surveys were found to be unreliable. Excluding reports identified as unreliable from these analyses did not alter the observed trends in either age at first sex or age at marriage. Tracing birth cohorts as they aged revealed reporting biases, particularly among the youngest cohorts. Comparisons by birth cohorts, which span a period of >40 years, indicate that median age at first sex has remained constant over time for women but has declined gradually for men. CONCLUSIONS: Although many reports of age at first sex and age at marriage were found to be unreliable, inclusion of such reports did not result in artificial generation or suppression of trends.

Fewer partners or more condoms? Modelling the effectiveness of STI prevention interventions.

BACKGROUND: Some advocates of HIV prevention have counterposed programmes aimed at reducing numbers of sex partners to programmes aimed at increasing condom use. In this polarised debate, arguments about their relative effectiveness have been based on limited evidence. OBJECTIVES: To explore the theoretical impact of changing partner acquisition rates and condom use on the population level incidence of sexually transmitted infections different in different populations. METHODS: A standard deterministic compartmental model of the transmission dynamics of a sexually transmitted disease is solved numerically. The change in behaviour required to prevent a single case of infection is calculated for a range of scenarios. RESULTS: When the transmission probability per sex act is low across partnerships, the incidence of infection responds similarly to changes in partner numbers and numbers of unprotected sex acts. High transmission probabilities alter the relationships, with the effectiveness of increasing condom use improving as the background number of unprotected sex acts decreases. The divergence in patterns of impact is marked when there is heterogeneity in the transmission probability per act across partnerships. CONCLUSIONS: Both reducing numbers of sex partners and increasing condom use can lower the incidence of sexually transmitted infections. Unfortunately, there is no simple and general rule that will allow the efficiency of interventions to be calculated. Heterogeneity in transmission probability across infections, which may occur for both bacterial and viral infections, can reduce the effectiveness of condom use as an intervention if that use is inconsistent.

Interpreting declines in HIV prevalence: impact of spatial aggregation and migration on expected declines in prevalence.

BACKGROUND: Declines in the prevalence of HIV might occur due to natural epidemic dynamics rather than changes in risk behaviour. Determining the cause of an observed decline is important in understanding the epidemiology of HIV. OBJECTIVE: To explore how patterns of recruitment and interactions between subpopulations in different areas influence the predicted decline in the prevalence of HIV in the absence of reductions in risk behaviour. METHODS: A deterministic mathematical model of the heterosexual transmission of HIV in high prevalence endemic settings incorporating various patterns of recruitment to high-risk behaviour groups, population growth and migration was solved numerically. The possibility that apparent trends are generated or obscured through aggregating data from across areas experiencing different epidemics is also considered. RESULTS: Declines in the prevalence of HIV can occur even if individuals do not change behaviour, raising the possibility that epidemic downturns could be wrongly attributed to interventions. This effect is greatest when individuals do not enter higher risk groups to compensate for reductions in size caused by deaths from AIDS and when migration is non-random with respect to risk or infectious status and migration patterns change as the epidemic matures. In contrast, aggregating prevalence data from subregions with different epidemic profiles tends to mask declines in prevalence. CONCLUSIONS: Interpreting surveillance data is important in understanding widespread responses to HIV epidemics. The results show that understanding patterns of adoption of risk behaviours and patterns of migration is important in interpreting declines in the prevalence of HIV.

Demographic impact of the HIV epidemic in Thailand.

OBJECTIVE: To assess the impact of the HIV epidemic on the demographic development of the Thai population. METHODS: A deterministic mathematical model was used to predict simultaneously epidemiological and demographic processes. Partial differential equations express the relationships between biological, behavioural and demographic variables. The model allows the evaluation of different sexual mixing patterns, variable transmission probabilities and incubation times. Validity analysis was performed by generating antecedent HIV prevalence patterns among military recruits and pregnant women. RESULTS: On the national level in Thailand we predict that the cumulative number of people in Thailand with HIV infection will exceed 1 million by 1999; the number of deaths from AIDS will be 555000 by the year 2000 but will not reach 1 million until after the year 2014. Without the HIV epidemic the population growth rate was estimated at 1.3% per annum until 1995, after which a decline to 0.9% by 2005 is predicted. The HIV epidemic started to affect the population growth rate by 0.026% per year in 1991, and the difference is predicted to rise to about 0.12% per year during the period 1995-2000, to decline to 0.06% in 2005 and then to disappear. In the mid-1990s HIV affected mainly the 15-35-year-old age group, but over time younger and older age groups have been affected as a result of perinatal transmission, and a decline in fertility as well as ageing of the 15-35-year-old birth cohort. Because of HIV, in 2000 there will be 612000 (1%) fewer people than expected and by 2010, 1140000 fewer (1.6%). We predict that the demographic impact of the HIV epidemic in the northern region will follow the same pattern, but with greater severity. Here, the effect on the population growth rate and the population age distribution is likely to be twice as high as at the national level. CONCLUSIONS: It is estimated that 1 million Thais will be infected with HIV by the year 2000 and an almost equal number will have died of AIDS by the year 2014. Although these numbers seem high, their direct and indirect effects on the demographic structure of the Thai population are small. However, at a regional level, for example in the northern region, the effect of the HIV epidemic may be more severe.

Reductions in risk behaviour provide the most consistent explanation for declining HIV-1 prevalence in Uganda.

OBJECTIVE: To monitor the HIV-1 epidemic in Western Uganda and the possible impact of interventions. DESIGN: Results from sentinel surveillance of HIV-1 seroprevalence were compared with cross-sectional serosurvey data and model simulations. METHODS: Age-specific trends in HIV-1 prevalence between 1991 and 1997 amongst antenatal clinic (ANC) attenders in the town of Fort Portal, where a comprehensive AIDS control programme has been implemented since 1991, were analysed. Results were compared with outputs from a mathematical model simulating the HIV-1 epidemic in Uganda. Two scenarios were modelled: one without and one with behaviour change. Sentinel surveillance data were compared with data from a population-based HIV-1 serosurvey at the study site, which was carried out in early 1995. RESULTS: Data from 3271 ANC attenders identified greater education and being single as risk factors for HIV-1 infection. A significant decrease of risk for women with secondary school education over time was observed, whereas the risk for illiterate women remained high. Among women aged 15-19 years (n = 1045) education and marital status-adjusted HIV-1 prevalence declined steadily from 32.2% in 1991 to 10.3% in 1997. For 20-24-year-old women (n = 1010) HIV-1 prevalence increased until 1993 from 19.9% to 31.7% and decreased thereafter (21.7% in 1997). These trends closely follow the prediction of the model simulation assuming behaviour change, and for 1995-1997, confidence intervals of the HIV-1 prevalence estimate exclude the model output for an uninfluenced epidemic. No clear trends of HIV-1 prevalence were found in older women (n = 1216) and comparisons with the model were ambiguous. Sentinel surveillance data at the time of the population survey closely reflected results for the female general population sample for the two younger age-groups (15-19 and 20-24 years). In contrast, pregnant women aged 25-29 years showed significantly lower rates than the population sample (20.8% versus 45.1%). CONCLUSION: HIV-1 prevalence amongst ANC attenders aged 15-24 years can be used to monitor the HIV-1 epidemic in the given setting. Declining trends of HIV-1 prevalence in women aged 15-19 and 20-24 years most likely correspond to a reduced HIV-1 incidence attributable to changes in behaviour. Our data also show that sentinel surveillance data need to be age-stratified to give useful information.

Magic bullets need accurate guns--syphilis eradication, elimination, and control.

When cases of early syphilis are treated promptly, the spread of the bacteria within a population is interrupted. However, if complacency is induced by successful control, then upsurges in syphilis incidence can occur. The methods and aims of syphilis control in industrialised countries are reviewed in the light of the potential for regional elimination and global eradication programmes. While the medical means to eliminate syphilis are at hand, acceptable means for finding and treating cases that transmit infection need to be developed, particularly in the marginalized communities with limited access to care.

Is HIV-1 likely to become a leading cause of adult mortality in sub-Saharan Africa?

Concerns are sometimes expressed at the extent to which HIV-1 is prioritized within international and national health budgets and as a research issue, on the grounds that much larger numbers of people in developing countries currently die from other diseases, such as malaria and tuberculosis. We use a previously described mathematical model to explore how the HIV-1 epidemic could develop within a sub-Saharan African context and investigate the trends and patterns of adult mortality which could follow. Two contrasting scenarios are studied, one which turns population growth rates negative and another which does not. In both cases, HIV-1-related disease accounts for over 75% of annual deaths among men and women aged 15-60 years by year 25 of the epidemic. Relatively little change in mortality is seen in the early years of the simulated epidemics. However, by year 15, expectation of life at age 15 has fallen from 50 to below 30 years. The fragmentary evidence now available from empirical studies supports the impression that HIV-1 is rapidly emerging as a leading cause of adult deaths in areas of sub-Saharan Africa. Observed patterns of age-dependent mortality reflect those projected in the model simulations.

Potential impact of low efficacy HIV-1 vaccines in populations with high rates of infection.

A safe and effective HIV vaccine to prevent infection and/or to moderate disease is urgently needed. Research progress has been slower than anticipated for a variety of reasons including uncertainty over which immunogen to use (i.e. recombinant subunit envelope proteins or whole HIV-1 products), confusion on which immunological markers best correlate with protection, the relevance of the HIV-1 chimpanzee model to infection in humans and the significance of the rapid evolution of HIV-1, with different clades of the virus emerging in different parts of the world. However, what some would interpret as encouraging results, from Phase I and II trials of recombinant envelope glycoprotein vaccines, have raised the question of whether the time is right to start Phase III trials in humans with immunogens that may have low to moderate efficacy. By using mathematical models and data from epidemiological studies, we examine the potential impact of such vaccines within heterosexual communities with high rates of infection. Analyses suggest that it will be difficult to block HIV-1 transmission even with very high levels of mass vaccination. The cost of sustaining high levels of herd immunity with a vaccine of short protection duration is likely to be high. However, assessments of impact over the long duration of an HIV-1 epidemic indicate that many cases of HIV infection and associated mortality can be prevented by immunogens with efficacy of 50% or less and a five year protection duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Gonococcal infection and human fertility in sub-Saharan Africa.

An analysis is presented of the influence of Neisseria gonorrhoeae on human population growth in regions of sub-Saharan Africa where gonococcal infections are prevalent in sexually active adults. Combining epidemiological and demographic data within the framework of a mathematical model, we show that gonorrhoea has a major impact on fertility and, concomitantly, on net population growth in areas with a high prevalence of untreated infections. Specifically, a 20% prevalence in sexually active adults is predicted to induce a 50% reduction in net population growth. Model predictions are in good agreement with observed data from Uganda, and the sensitivity of the prediction to various complications, such as heterogeneity in sexual behaviour, is assessed. The analysis suggests that the predicted increase in fertility arising from expanded sexually transmitted disease (STD) control programmes in Africa to help combat the spread of human immunodeficiency viruses (HIV-1 and HIV-2) will help to offset the predicted demographic impact of AIDS in the worst afflicted areas. In other areas the rise in fertility associated with effective STD control will need to be countered by the linkage of STD control programmes with family planning initiatives.

Public health paradoxes and the epidemiological impact of an HPV vaccine.

BACKGROUND: our understanding of human papilloma virus (HPV) and cervical cancer has improved dramatically, with a vaccine against the viral infection being a real possibility in the near future. AIMS: the goal of an HPV vaccine would be to reduce the prevalence of infection and hence the risk of cervical abnormalities. However, questions arise as to how this would interact with an existing intervention, screening, which reduces the progress of cervical abnormalities to serious disease. Furthermore, will a vaccine against one genotype influence the other types within a population and will the patterns of infection and disease remain the same if the vaccine alters the timing and type of HPVs experienced within a population? What would a vaccine that only worked in one sex achieve and how widespread would the use of such a vaccine have to be? CONCLUSION: the above-given questions can be addressed within a theoretical framework that describes the transmission dynamics of human papilloma virus.

No reason for complacency about the potential demographic impact of AIDS in Africa.

Much uncertainty surrounds the likely demographic impact of AIDS in the worst afflicted regions of the developing world such as sub-Saharan Africa. Various research groups have published projections of future trends but these differ widely with respect to potential impact on net population growth rates. Pessimistic forecasts suggest that AIDS may reverse the sign of a 3% to 4% population growth rate before the establishment of HIV, over time periods of a few to many decades. Optimistic forecasts suggest a decline in population growth rates, but predict that a 3% growth rate before AIDS may be reduced by only about 50% over a period of a few decades. This paper reports new analyses of the demographic impact of AIDS, based on observed age-stratified prevalences of HIV-1 infection amongst women of child bearing age. It is assumed that the observed patterns reflect the final endemic state and the implications of this assumption for adult and infant mortality and female reproductive life expectancy are assessed. It is concluded that a variety of scenarios is possible, depending on the detail of assumptions concerning life expectancy before the arrival of AIDS, the incubation period of the disease, and the rate of vertical transmission. Realistic assumptions do suggest, however, that the observed prevalences of infection in the worst afflicted regions of sub-Saharan Africa are sufficient to reduce current population growth rates to close to, or below, zero in the coming decades.

The seasonal pattern of dengue in endemic areas: mathematical models of mechanisms.

In dengue-endemic areas such as Thailand, there is clear seasonality in the number of reported cases of dengue virus disease. However, the roles of different entomological and biological variables in determining this pattern have not been ascertained. To investigate this, seasonally-varying parameters were introduced in a step-wise fashion into a mathematical model of the transmission dynamics of dengue viruses. The predicted prevalence of infection was then compared to observed seasonal patterns of disease. The strongest influences on the pattern of infection and its seasonal variation were duration of infectiousness of the host, vector mortality, and biting rate. However, seasonally-varying parameters such as the latent period of infection in the vector had to be incorporated into the model to generate the correct timing of peak infection prevalence. A few limiting variables usually control the prevalence of an infectious disease because small changes in their values can carry the infection beyond the threshold at which its basic reproductive number is one. It was changes in such parameters (vector biting and mortality rate) which caused seasonal prevalence, but the timing of peak prevalence was a result of time delays within the system.

A rural HIV epidemic in Zimbabwe? Findings from a population-based survey.

The aim of the study was to use population-based data from 689 adults to describe the socio-demographic, behavioural and biomedical correlates of HIV infection and aid identification of effective HIV control strategies for rural Zimbabwe. Dried blood spot and urine samples were collected for HIV and sexually transmitted disease (STD) testing and participants were interviewed on socio-demographic characteristics, sexual behaviour and experience of STD symptoms. HIV seroprevalence was 23.3% and was higher in females, divorcees, widows, working men, estate residents, and respondents reporting histories of STD symptoms. Female HIV seroprevalence rises sharply at ages 16-25. A third of sexually-active adults had experienced STD-associated symptoms but there were delays in seeking treatment. Herpes simplex virus type 2 (HSV-2) and Trichomonas vaginalis are more common causes than syphilis, gonorrhoea, and chlamydia, and are strongly associated with HIV infection. Local programmes promoting safer sexual behaviour and fast and effective STD treatment among young women, divorcees and working men could reduce the extensive HIV transmission in rural communities.

The basic reproductive rate of infection and the course of HIV epidemics.

The basic reproductive rate is a measure of the potential for growth of an infectious disease epidemic and depends on the pattern of infectious contacts within the host population, the likelihood of infection being transmitted during a contact, and the duration of infectiousness. These three variables are reviewed along with the surveillance data that records the progress of the epidemic, with an emphasis on the HIV-1 epidemic in heterosexual populations in developing countries. The problems with sentinel surveillance data for HIV infection mean that our knowledge of HIV incidence is poor. However, what is clear is that HIV has spread widely in heterosexual populations in sub-Saharan Africa. The scale of the demographic impact seen here will depend on the local AIDS incubation period with a shorter period generating a more acute demographic impact. Heterogeneity in sexual behaviour is vital to generate a high sexual activity "core group" within which HIV spreads rapidly. How far out of this core group the virus will spread depends on the patterns of mixing within populations. Interventions to reduce the incidence of HIV work through reducing the reproductive rate of the virus. To be efficient, these interventions have to be targeted at those most likely to spread the virus.