Geoffrey P. Garnett

A systematic review of the epidemiologic interactions between classic sexually transmitted diseases and HIV: how much really is known?

Background Many studies have explored the role of “classic” sexually transmitted diseases (STDs) in determining the pattern of HIV epidemics. However, the many different STDs may contribute in different ways, at different magnitudes. Goal To review available studies on the bidirectional interactions of HIV and STDs to explore the extent of current knowledge on the different influences of the varied STDs in heterosexual HIV epidemics. Methods Longitudinal studies on susceptibility and controlled studies on infectiousness and duration of disease identified on electronic databases through reference lists and citation indices up to the end of 1999 were systematically reviewed, including meta-analyses assessing the influence of STDs on susceptibility to HIV. Results Studies have a clear publication bias with a significant result that hinders robust interpretation. However, genital ulcerative disease appears to have a greater impact than nonulcerative disease, and men are more affected than women by the effects of STDs on susceptibility to HIV. There is evidence that STDs increase the infectiousness of HIV from men to women, whereas the evidence is more equivocal for the infectiousness of women. Few studies identify the impact of different STDs, and there is a marked lack of studies investigating the impact of HIV infection on the transmission of other STDs. Conclusions A large body of work has measured the association between STDs and HIV. However, publication bias and gaps in the focus of studies mean that a detailed, quantitative understanding of the interaction requires much more attention.

Prospects for worldwide tuberculosis control under the WHO DOTS strategy

BACKGROUND WHO advocates the use of directly observed treatment with a short-course drug regimen as part of the DOTS strategy, but the potential effect of this strategy worldwide has not been investigated. METHODS We developed an age-structured mathematical model to explore the characteristics of tuberculosis control under DOTS, and to forecast the effect of improved case finding and cure on tuberculosis epidemics for each of the six WHO regions. FINDINGS In countries where the incidence of tuberculosis is stable and HIV-1 absent, a control programme that reaches the WHO targets of 70% case detection and 85% cure would reduce the incidence rate by 11% (range 8-12) per year and the death rate by 12% (9-13) per year. If tuberculosis has been in decline for some years, the same case detection and cure rates would have a smaller effect on incidence. DOTS saves a greater proportion of deaths than cases, and this difference is bigger in the presence of HIV-1. HIV-1 epidemics cause an increase in tuberculosis incidence, but do not substantially reduce the preventable proportion of cases and deaths. Without greater effort to control tuberculosis, the annual incidence of the disease is expected to increase by 41% (21-61) between 1998 and 2020 (from 7.4 million to 10.6 million cases per year). Achievement of WHO targets by 2010 would prevent 23% (15-30) or 48 million cases by 2020. INTERPRETATION The potential effect of chemotherapy (delivered as DOTS) on tuberculosis is greater in many developing countries now than it was in developed countries 50 years ago. To exploit this potential, case detection and cure rates urgently need to be improved in the main endemic areas.

Towards an improved investment approach for an effective response to HIV/AIDS

Substantial changes are needed to achieve a more targeted and strategic approach to investment in the response to the HIV/AIDS epidemic that will yield long-term dividends. Until now, advocacy for resources has been done on the basis of a commodity approach that encouraged scaling up of numerous strategies in parallel, irrespective of their relative effects. We propose a strategic investment framework that is intended to support better management of national and international HIV/AIDS responses than exists with the present system. Our framework incorporates major efficiency gains through community mobilisation, synergies between programme elements, and benefits of the extension of antiretroviral therapy for prevention of HIV transmission. It proposes three categories of investment, consisting of six basic programmatic activities, interventions that create an enabling environment to achieve maximum effectiveness, and programmatic efforts in other health and development sectors related to HIV/AIDS. The yearly cost of achievement of universal access to HIV prevention, treatment, care, and support by 2015 is estimated at no less than US

An estimate of the global prevalence and incidence of herpes simplex virus type 2 infection

22 billion. Implementation of the new investment framework would avert 12·2 million new HIV infections and 7·4 million deaths from AIDS between 2011 and 2020 compared with continuation of present approaches, and result in 29·4 million life-years gained. The framework is cost effective at

Role of Herd Immunity in Determining the Effect of Vaccines against Sexually Transmitted Disease

1060 per life-year gained, and the additional investment proposed would be largely offset from savings in treatment costs alone.

Declines in HIV prevalence can be associated with changing sexual behaviour in Uganda, urban Kenya, Zimbabwe, and urban Haiti

OBJECTIVE To estimate the global prevalence and incidence of herpes simplex virus type 2 (HSV-2) infection in 2003. METHODS A systematic review was undertaken of published seroprevalence surveys describing the prevalence or incidence of HSV-2 by age and gender. For each of 12 regions, pooled prevalence values by age and gender were generated in a random-effect model. HSV-2 incidence was then estimated from these pooled values using a constant-incidence model. Values of the HSV-2 seroprevalence from the model fits were applied to the total population to estimate the numbers of people infected. FINDINGS The total number of people aged 15-49 years who were living with HSV-2 infection worldwide in 2003 is estimated to be 536 million, while the total number of people who were newly infected with HSV-2 in 2003 is estimated to be 23.6 million. While the estimates are limited by poor availability of data, general trends are evident. For example, more women than men were infected, and the number infected increased with age. Although prevalence varied substantially by region, predicted prevalence was mostly higher in developing regions than developed regions. CONCLUSION The prevalence of HSV-2 is relatively easy to measure since infection is lifelong and has a specific serological test. The burden of disease is less easy to quantify. Despite the often sparse data on which these estimates are based, it is clear that HSV-2 infection is widespread. The dramatic differences in prevalence between regions are worthy of further exploration.

Host immunity and synchronized epidemics of syphilis across the United States

BACKGROUND Vaccination programs provide both direct protection to those immunized and herd immunity, which is indirect protection of those who remain susceptible, owing to a reduced prevalence of infections. METHODS The well-understood impact of vaccination against ubiquitous childhood infections is compared with that of vaccination against sexually transmitted infections (STIs), and theoretical insights are derived from a review of mathematical modeling studies. RESULTS Typically, a large fraction of cases of STIs are acquired by those with modest risk, and these cases could be prevented by low-efficacy vaccines. If coverage is good, vaccination of only one sex can protect the other sex. Candidate vaccines against human papillomavirus (HPV) and genital herpes are in the final stages of testing. The former is likely to be highly efficacious for a limited number of disease-causing HPV types, and the latter has provided protection against disease in women who initially were seronegative for both herpes simplex virus (HSV) type 1 and HSV-2, with 73% efficacy. In models, this vaccine had a substantial impact when infectiousness was assumed to be reduced along with incidence of disease. CONCLUSION With such vaccines on the horizon, the requirements for vaccine delivery need to be considered, particularly who should be vaccinated and at what age.

HIV infection and reproductive health in teenage women orphaned and made vulnerable by AIDS in Zimbabwe

Objective: To determine whether observed changes in HIV prevalence in countries with generalised HIV epidemics are associated with changes in sexual risk behaviour. Methods: A mathematical model was developed to explore the relation between prevalence recorded at antenatal clinics (ANCs) and the pattern of incidence of infection throughout the population. To create a null model a range of assumptions about sexual behaviour, natural history of infection, and sampling biases in ANC populations were explored to determine which factors maximised declines in prevalence in the absence of behaviour change. Modelled prevalence, where possible based on locally collected behavioural data, was compared with the observed prevalence data in urban Haiti, urban Kenya, urban Cote d’Ivoire, Malawi, Zimbabwe, Rwanda, Uganda, and urban Ethiopia. Results: Recent downturns in prevalence observed in urban Kenya, Zimbabwe, and urban Haiti, like Uganda before them, could only be replicated in the model through reductions in risk associated with changes in behaviour. In contrast, prevalence trends in urban Cote d’Ivoire, Malawi, urban Ethiopia, and Rwanda show no signs of changed sexual behaviour. Conclusions: Changes in patterns of HIV prevalence in urban Kenya, Zimbabwe, and urban Haiti are quite recent and caution is required because of doubts over the accuracy and representativeness of these estimates. Nonetheless, the observed changes are consistent with behaviour change and not the natural course of the HIV epidemic.

Modeling the impact of HIV chemoprophylaxis strategies among men who have sex with men in the United States: HIV infections prevented and cost-effectiveness

A central question in population ecology is the role of ‘exogenous’ environmental factors versus density-dependent ‘endogenous’ biological factors in driving changes in population numbers. This question is also central to infectious disease epidemiology, where changes in disease incidence due to behavioural or environmental change must be distinguished from the nonlinear dynamics of the parasite population. Repeated epidemics of primary and secondary syphilis infection in the United States over the past 50 yr have previously been attributed to social and behavioural changes. Here, we show that these epidemics represent a rare example of unforced, endogenous oscillations in disease incidence, with an 8–11-yr period that is predicted by the natural dynamics of syphilis infection, to which there is partially protective immunity. This conclusion is supported by the absence of oscillations in gonorrhoea cases, where a protective immune response is absent. We further demonstrate increased synchrony of syphilis oscillations across cities over time, providing empirical evidence for an increasingly connected sexual network in the United States.

Effects of unconditional and conditional cash transfers on child health and development in Zimbabwe: a cluster-randomised trial

Abstract AIDS has increased the number of orphans and vulnerable children (OVCs) in sub-Saharan Africa who could suffer detrimental life experiences. We investigated whether OVCs have heightened risks of adverse reproductive health outcomes including HIV infection. Data on HIV infection, sexually transmitted infection (STI) symptoms and pregnancy, and common risk factors were collected for OVCs and non-OVCs in a population survey of 1523 teenage children in eastern Zimbabwe between July 2001 and March 2003. Multivariate logistic regression was used to test for statistical association between OVC status, adverse reproductive health outcomes and suspected risk factors. Amongst women aged 15–18 years, OVCs had higher HIV prevalence than non-OVCs (3.2% versus 0.0%; p=0.002) and more common experience of STI symptoms (5.9% versus 3.3%; adjusted odds ratio = 1.75, 95% CI 0.80–3.80) and teenage pregnancy (8.3% versus 1.9%; 4.25, 1.58–11.42). OVCs (overall), maternal orphans and young women with an infected parent were more likely to have received no secondary school education and to have started sex and married, which, in turn, were associated with poor reproductive health. Amongst men aged 17–18 years, OVC status was not associated with HIV infection (0.5% versus 0.0%; p=1.000) or STI symptoms (2.7% versus 1.6%; p=0.529). No association was found between history of medical injections and HIV risk amongst teenage women and men. High proportions of HIV infections, STIs and pregnancies among teenage girls in eastern Zimbabwe can be attributed to maternal orphanhood and parental HIV. Many of these could be averted through further female secondary school education. Predicted substantial expanded increases in orphanhood could hamper efforts to slow the acquisition of HIV infection in successive generations of young adults, perpetuating the vicious cycle of poverty and disease.