Prospects for worldwide tuberculosis control under the WHO DOTS strategy. Directly observed short-course therapy.

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.

Sampling biases and missing data in explorations of sexual partner networks for the spread of sexually transmitted diseases.

The structures of sexual partner networks are important in determining patterns of transmission of STDs including HIV. Empirical data on sexual partnerships and sexual partner networks collected through sampling individuals are a non-random sample of partnerships and network structures even if individuals are sampled randomly. This has the potential to bias estimates of measures describing the sexual partner network.

Mathematical models of Haemophilus influenzae type b.

A review of empirical studies and the development of a simple theoretical framework are used to explore the relationship between Haemophilus influenzae type b (Hib) carriage and disease within populations. The models emphasize the distinction between asymptomatic and symptomatic infection. Maximum likelihood methods are used to estimate parameter values of the models and to evaluate whether models of infection and disease are satisfactory.

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 natural history of syphilis. Implications for the transmission dynamics and control of infection.

Background: Syphilis remains a significant cause of morbidity in many developing countries and in some areas within North America and Europe. Mathematical models of the transmission dynamics of sexually transmitted infections have provided insights of relevance both to the interpretation of observed epidemiological patterns and to the design of control programs. Their use for the study of syphilis has been limited to date.

Heterogeneities in the transmission of infectious agents: implications for the design of control programs.

From an analysis of the distributions of measures of transmission rates among hosts, we identify an empirical relationship suggesting that, typically, 20% of the host population contributes at least 80% of the net transmission potential, as measured by the basic reproduction number, R0. This is an example of a statistical pattern known as the 20/80 rule. The rule applies to a variety of disease systems, including vector-borne parasites and sexually transmitted pathogens.

The role of sexual partnership networks in the epidemiology of gonorrhea.

Background: Empirical studies have the potential to collect data on patterns of sexual mixing and network structures.

Goal: To explore the contribution of different network measures in sexually transmitted disease epidemiology.

Study Design: Individual-based stochastic simulations of a network of sexual partnerships and sexually transmitted disease transmission are analyzed using logistic regression.

Sexual partner networks in the transmission of sexually transmitted diseases. An analysis of gonorrhea cases in Sheffield, UK.

Background And Objectives: Routine contact tracing data on patients with gonorrhea are used to identify sexual partner networks. These are combined with gonococcal typing data to study patterns of transmission. The role of persons in transmission is discussed.

Low-efficacy HIV vaccines: potential for community-based intervention programmes.

To combat the spread of HIV, progress on vaccine development is eagerly awaited. Haynes in this series has described the progress made so far with various vaccine types. This article describes how mathematical modelling techniques can be used to predict the likely impact of low-efficacy vaccines in community transmission of the virus.

Sexually transmitted diseases and sexual behavior: insights from mathematical models.

The major role of mathematical models of transmission dynamics and population biology of sexually transmitted diseases is helping understand the influence of the many biologic, social, and behavioral factors that influence the incidence or prevalence of infection. Various models can examine heterogeneity in sexual behavior and determine how individual variation influences epidemiologic pattern within a population. In the cases of heterogeneity in sex acts and in sex partner numbers, heterogeneity acts to enhance the likelihood of the persistence of infection.

Mass vaccination to control chickenpox: the influence of zoster.

The impact of transmission events from patients with shingles (zoster) on the epidemiology of varicella is examined before and after the introduction of mass immunization by using a stochastic mathematical model of transmission dynamics. Reactivation of the virus is shown to damp stochastic fluctuations and move the dynamics toward simple annual oscillations. The force of infection due to zoster cases is estimated by comparison of simulated and observed incidence time series.

Antiviral therapy and the transmission dynamics of HIV-1.

The factors influencing the transmission dynamics of HIV are discussed in the context of the community wide use of antiviral therapy. A mathematical framework is constructed to examine the impact of chemotherapy on transmission, based on a description of the progressive decline of CD4 counts in infected patients. Treatment which acts to increase the incubation period before the onset of serious immunodeficiency, but has no impact on the infectiousness of a patient, is obviously beneficial to the individual.

Sexual mixing patterns of patients attending sexually transmitted diseases clinics.

Background: Theorectical studies have highlighted the importance of patterns of choice of sex partner in the transmission and persistence of sexually transmitted diseases (STDs).

Goal: To describe reported patterns of sexual mixing according to numbers of sex partners in STD clinics.

Study Design: Patients attending public health clinics in Seattle, Washington were interviewed about their own and their partners' behaviors.

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.

Strategies for limiting the spread of HIV in developing countries: conclusions based on studies of the transmission dynamics of the virus.

Possible interventions to reduce the spread of human immunodeficiency virus (HIV) include actions that attempt to alter sexual behaviour, such as education aimed at reducing the rate at which individuals acquire new sexual partners, and methods that reduce the probability of transmission between partners, such as the promotion of condom use and the treatment of so-called "cofactor" sexually transmitted diseases. A mathematical model of HIV transmission that is able to mimic different approaches to the control of HIV transmission is employed to study the relative values of different approaches, either used in isolation, or in combination. The nonlinear nature of the term that describes the per capita rate of transmission dictates that for a given degree of intervention, the benefit accruing in terms of reduced HIV spread depends on the prevalence of infection before the introduction of control.

Revealing the history of infectious disease epidemics through phylogenetic trees.

Phylogenetic trees play an increasing role in molecular epidemiology, where they have been used to understand the forces that shape patterns of viral sequence diversity. Phylogenetic trees can also be used to trace the dynamics of viral transmission within populations. Case studies document the worldwide spread of Human Immunodeficiency Virus type 1 (HIV-1) and hepatitis C virus (HCV).

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.

Genes, trees and infections: Molecular evidence in epidemiology.

Molecular phylogenies constitute an important new way of tracking the progress of viral epidemics. The phylogenetic analysis of viral sequence data provides information on the origin, spread and maintenance of infections and can be used to reconstruct contact networks of infected individuals. Analysis of the branching structure of phylogenetic trees also allows inferences to be made about the rate of transmission and the distinction between endemic and epidemic infections, and provides estimates of the numbers of infected individuals.

Balancing sexual partnerships in an age and activity stratified model of HIV transmission in heterosexual populations.

A mathematical model of the transmission dynamics of HIV-1 in a heterosexual population stratified by age, sex, and sexual activity (defined by rates of sexual partner acquisition) is presented. The model represents an extension of previous studies with a special focus on patterns of mixing or contact between sexual activity and different age classes of the two sexes. A range of mixing patterns between these groups is specified for both sexes.

Determinants of the demographic impact of HIV-1 in sub-Saharan Africa: the effect of a shorter mean adult incubation period on trends in orphanhood.

Recent evidence suggests that the adult HIV-1 incubation period may be shorter in some sub-Saharan African populations than in Western populations. In this article we use mathematical-model-based simulations to show that, other things being equal, a shorter incubation period can result in smaller but more pronounced HIV-1 epidemics and faster, more acute, changes in demographic features, such as adult mortality, orphanhood and population structure. Empirical studies of orphanhood reveal similar patterns to those found in the simulations, but suggest that migration patterns and structural factors can give rise to greater concentrations of orphans in areas of relatively low HIV-1 prevalence.