Sally Blower

• Lundquist Institute

Multiple phylogenetic studies of HIV in sub-Saharan Africa have shown that mobility-driven transmission frequently occurs: many communities export and import strains. Mobility-driven transmission can result in source-sink dynamics: one community can sustain a micro-epidemic in another community in which transmission is too low to be self-sustaining...

Background: In sub-Saharan Africa, where ~ 25 million individuals are infected with HIV and transmission is predominantly heterosexual, there is substantial geographic variation in the severity of epidemics. This variation has yet to be explained. Here, we propose that it is due to geographic variation in the size of the high-risk group (HRG): the...

UNAIDS has identified the Danish HIV epidemic in men who have sex with men (MSM) as a priority for elimination. Incidence is close to the elimination threshold of one new infection per year per 1,000 individuals. However, surveillance data show that HIV strains are being imported into Denmark, mainly due to travel. We use a transmission model to pr...

Background Approximately 25.5 million individuals are infected with HIV in sub-Saharan Africa (SSA). Epidemics in this region are generalized, show substantial geographic variation in prevalence, and are driven by heterosexual transmission; populations are highly mobile. We propose that generalized HIV epidemics should be viewed as a series of micr...

Detailed geospatial mapping of a generalized HIV epidemic in sub-Saharan Africa shows that implementing the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 strategy could potentially exacerbate urban-rural health care disparities.

Treatment as prevention (TasP) has been proposed by the World Health Organization and the Joint United Nations Programme on HIV/AIDS (UNAIDS) as a global strategy for eliminating HIV. The rationale is that treating individuals reduces their infectivity. We present a geostatistical framework for designing TasP-based HIV elimination strategies in sub...

Background: Worldwide, approximately 35 million individuals are infected with HIV; about 25 million of these live in sub-Saharan Africa. WHO proposes using treatment as prevention (TasP) to eliminate HIV. Treatment suppresses viral load, decreasing the probability an individual transmits HIV. The elimination threshold is one new HIV infection per...

Using census data we identify geographic patterns in residency changes in Lesotho over a decade. Using kriging to spatially interpolate data from 8,510 households we identify regions where households have members temporarily living away from home (divided households). Further, using a multivariate analysis and data from 2,026 couples we determine w...

We analyzed georeferenced data on mobility and HIV infection from the 2009 Demographic and Health Survey of Lesotho. We found; 50% of the population traveled in the preceding year. By constructing gender-specific mobility maps, we discovered that travel is highest in the urban areas bordering South Africa and in the mountainous interior of the coun...

Antiretroviral (ARV)-based pre-exposure HIV interventions may soon be rolled out in resource-constrained Sub-Saharan African countries, but rollout plans have yet to be designed. Here we use geospatial modelling and optimization techniques to compare two rollout plans for ARV-based microbicides in South Africa: a utilitarian plan that minimizes inc...

The most severe HIV epidemics worldwide occur in Lesotho, Botswana and Swaziland. Here we focus on the Lesotho epidemic, which has received little attention. We determined the within-country heterogeneity in the severity of the epidemic, and identified the risk factors for HIV infection. We also determined whether circumcised men in Lesotho have ha...

Treating HIV-infected individuals reduces their viral load, consequently increasing their survival time and decreasing their infectivity. It has been proposed that universal testing and treatment (i.e., universal "test & treat'') could lead to HIV elimination and would be extremely cost-effective. It is now being debated whether to use a universal...

In South Africa (SA) universal access to treatment for HIV-infected individuals in need has yet to be achieved. Currently ∼1 million receive treatment, but an additional 1.6 million are in need. It is being debated whether to use a universal 'test and treat' (T&T) strategy to try to eliminate HIV in SA; treatment reduces infectivity and hence trans...

Flow diagrams describing the structure of the Granich et al. model [1] (a) and our mathematical model (Equations 1–10) in the absence of drug resistance (b). The population is divided into susceptible (S), infected and untreated (I) and infected individuals receiving first-line therapy (A). The relative infectivity in each stage is denoted by λ. Ti...

Description of the mathematical model and derivation of the Control Reproduction Number. (DOCX)

Historical HIV incidence in South Africa generated by our mathematical model. Our mathematical model (Equations 1–10) is parameterized to account for the pre-treatment era as well as for heterogeneity in sexual behavior [1], [4], [5]. (DOCX)

Parameterization of the mathematical model (Equations 1–10) for implementing the universal ‘test and treat’ (T&T) strategy and achieving universal access to treatment for South Africa. (DOCX)

Comparison of historical HIV prevalence data for South Africa and historical HIV prevalence generated by our mathematical model. Our mathematical model (Equations 1–10) is parameterized to account for the pre-treatment era as well as for heterogeneity in sexual behavior. Historical HIV prevalence is based on antenatal clinic data [1], [4], [5]. (DO...

We find interventions targeting serodiscordant couples (SDC) may not be feasible in countries where HIV prevalence is less than 5%, because only 3-19/1000 individuals are HIV-positive/negative and in SDC. Interventions may be feasible in countries where prevalence is greater than 10%, because 34-48/1000 individuals are HIV-positive/negative and in...

Transmission of HIV strains with drug-resistance mutations (DRMs) causes public health problems in resource-rich countries. We use a stochastic model, with data from viral competition experiments, to analyze the effect of fitness costs (FCs) and genetic bottlenecks on limiting transmission of 10 clinically significant DRMs. Transmission of DRMs wit...

Supplementary Information

Clinical trials have recently demonstrated the effectiveness of Pre-Exposure Prophylaxis (PrEP) in preventing HIV infection. Consequently, PrEP may soon be used for epidemic control. We model the dynamic interactions that will occur between treatment programs and potential PrEP interventions in resource-constrained countries. We determine the conse...

Supplementary Info File #1

The HPTN 052 study demonstrated a 96% reduction in HIV transmission in discordant couples using antiretroviral therapy (ART). To predict the epidemic impact of treating HIV-discordant couples to prevent transmission. Mathematical modeling to predict incidence reduction and the number of infections prevented. Demographic and epidemiological data fro...

Mathematical models are useful tools for understanding and predicting epidemics. A recent innovative modeling study by Stehle and colleagues addressed the issue of how complex models need to be to ensure accuracy. The authors collected data on face-to-face contacts during a two-day conference. They then constructed a series of dynamic social contac...

To quantify the potential impact of mass rape on HIV incidence in seven conflict-afflicted countries (CACs), with severe HIV epidemics, in sub-Saharan Africa. Uncertainty analysis of a risk equation model. A mathematical model was used to evaluate the potential impact of mass rape on increasing HIV incidence in women and girls in Burundi, Democrati...

This letter comments on the universal "test and treat" strategy to eliminate HIV in South Africa and stresses that this strategy would be extremely costly in terms of treatment alone but also requires substantial financial resources to pay for extensive prevention interventions and annual testing.

The administration of antiretrovirals before HIV exposure to prevent infection (i.e., preexposure prophylaxis; PrEP) is under evaluation in clinical trials. Because PrEP is based on antiretrovirals, there is considerable concern that it could substantially increase transmitted resistance, particularly in resource-rich countries. Here we use a mathe...

Predicting the impact of Pre-Exposure Prophylaxis Interventions in Botswana V Supervie, T Moeti, G Musuka, L Busang, S Blower Background: Botswana has one of the highest levels of HIV worldwide; by 2008, 25% of the 950,000 adults between 15 and 49 were infected. Effective prevention strategies are urgently needed. The administration of low levels o...

Recently, the promise of a new universal long-term flu vaccine has become more tangible than ever before. Such a vaccine would protect against very many seasonal and pandemic flu strains for many years, making annual vaccination unnecessary. However, due to complacency behavior, it remains unclear whether the introduction of such vaccines would mai...

Transmission of Drug Resistance Understanding the dynamics of drug-resistant strains of HIV and the key determinants affecting their evolution and spread is crucial for predicting future effects of drug treatment. Current models can only track one resistant strain, so Smith? et al. (p. 697 , published online 14 January) used empirical data from San...

In their recent Review (Waves of resistance: Staphylococcus aureus in the antibiotic era. Nature Rev. Microbiol. 7, 629–641 (2009)

Clearly air travel, by transporting infectious individuals from one geographic location to another, significantly affects the rate of spread of influenza A (H1N1). However, the possibility of within-flight transmission of H1N1 has not been evaluated; although it is known that smallpox, measles, tuberculosis, SARS and seasonal influenza can be trans...

Current measures of the clinical efficacy of antiretroviral therapy (ART) in the treatment of HIV include the change in HIV RNA in the plasma and the gain in CD4 cells. We propose new measures for evaluating the efficacy of treatment that is based upon combinations of non-nucleoside and nucleoside reverse transcriptase inhibitors. Our efficacy meas...

Here we present a review of the literature of influenza modeling studies, and discuss how these models can provide insights into the future of the currently circulating novel strain of influenza A (H1N1), formerly known as swine flu. We discuss how the feasibility of controlling an epidemic critically depends on the value of the Basic Reproduction...

Recently Granich et al. at the World Health Organization (WHO) concluded, using mathematical modeling, that HIV epidemics could be eliminated within a decade. They assumed all individuals would be tested annually and every infected individual (regardless of stage of infection) would be put on treatment. Based on this modeling study the WHO is consi...

We re-examine the evidence behind the controversial hypothesis that syphilis epidemics cycle. We used the same methods (spectral analysis) used by the proponents of this hypothesis to reanalyse a longitudinal dataset provided by the US Centers for Disease Control and Prevention (CDC). We also analysed a longitudinal CDC mortality dataset. To invest...

Vaginal microbicides, designed to prevent HIV infection in women, are one of the most promising biomedical interventions. Clinical trials of second-generation microbicides have begun; if shown to be effective, they could be licensed within 5-10 years. Because these microbicides contain antiretrovirals (ARVs), they could be highly effective. However...

Construction of an HIV risk map of Botswana: a spatial-based policy and planning tool J Okano, T Moeti, G Musuka, L Busang, S Blower Background: Botswana has one of the highest levels of HIV worldwide; by 2008, 25% of the 950,000 adults between 15 and 49 were infected. There are signifi cant differences in prevalence based on age and gender; furthe...

In high-income countries after World War II, the widespread availability of effective antimicrobial therapy, combined with expanded screening, diagnosis, and treatment programmes, resulted in a substantial decline in the incidence of syphilis. However, by the turn of the 21st century, outbreaks of syphilis began to occur in different subpopulations...

The objective of this project was to perform an inverse parameter identification study to determine parameter values in a system of ten ordinary differential equations modeling the prediction of the evolutionary spread of syphilis. The goal was to predict infant mortality rates due to syphilis by using this model and match them to actual field data...

The Centers for Disease Control (CDC) is currently attempting to eliminate syphilis in the United States (US); to ensure that their control strategies will be effective it is important to understand the transmission dynamics of syphilis. Epidemics of certain infectious diseases (e.g., influenza) can rise and fall with a well-defined periodicity; th...

Efforts are currently underway to develop therapeutic vaccines for Herpes Simplex Virus type 2 (HSV-2). We use a mathematical model to predict the potential public health impact of imperfect, therapeutic HSV-2 vaccines. We evaluate vaccine effectiveness and efficiency for the general population in the United States where HSV-2 prevalence is current...

Recently we have introduced an inductive reasoning game of voluntary yearly vaccination to establish whether or not a population of individuals acting in their own self-interest would be able to prevent influenza epidemics. Here, we analyze our model to describe the dynamics of the collective yearly vaccination uptake. We discuss the mean-field equ...

To illustrate the usefulness of mathematical models to the microbiology and medical communities, we explain how to construct and apply a simple transmission model of an emerging pathogen. We chose to model, as a case study, a large (>8,000 reported cases) on-going outbreak of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) i...

Rates of reactivation of herpes simplex virus type 2 (HSV-2) change over time and these changes affect transmission and clinical management strategies. We conducted a longitudinal study of HSV-2 infection to quantify rates of change in HSV-2 reactivation, mucosal shedding and recurrences of genital lesions, using a newly available model of HSV with...

Previous modeling studies have identified the vaccination coverage level necessary for preventing influenza epidemics, but have not shown whether this critical coverage can be reached. Here we use computational modeling to determine, for the first time, whether the critical coverage for influenza can be achieved by voluntary vaccination. We constru...

Antiretroviral therapy (ART) has prolonged and improved the lives of persons infected with HIV. Theoretically, it can also be used to prevent the transmission of HIV. The pharmacology of ART in the male and female genital tract can be expected to affect the success of the intervention, and ART agents differ considerably in their ability to concentr...

To predict the potential severity of outbreaks of infectious diseases such as SARS, HIV, TB and smallpox, a summary parameter, the basic reproduction number R(0), is generally calculated from a population-level model. R(0) specifies the average number of secondary infections caused by one infected individual during his/her entire infectious period...

The South African Government has outlined detailed plans for antiretroviral (ART) rollout in KwaZulu-Natal Province, but has not created a plan to address treatment accessibility in rural areas in KwaZulu-Natal. Here, we calculate the distance that People Living With HIV/AIDS (PLWHA) in rural areas in KwaZulu-Natal would have to travel to receive A...

The Botswana antiretroviral program began in 2002 and currently treats 42,000 patients, with a goal of treating 85,000 by 2009. The World Health Organization (WHO) has begun to implement a surveillance system for detecting transmitted resistance that exceeds a threshold of 5%. However, the WHO has not determined when this threshold will be reached....

Inspired by Minority Games, we constructed a novel individual-level game of adaptive decision-making based on the dilemma of deciding whether to participate in voluntary influenza vaccination programs. The proportion of the population vaccinated (i.e., the vaccination coverage) determines epidemic severity. Above a critical vaccination coverage, ep...

Antiretroviral therapy (ART) is becoming available in South Africa. Demand will exceed supply; thus, difficult decisions will have to be made in allocating ART. The majority of those treated for HIV are likely to be in cities, because health infrastructure and personnel are concentrated in urban centers. We predict the epidemiological impact of dru...

We evaluate the potential impact of rectal microbicides for reducing HIV transmission in bathhouses. A new mathematical model describing HIV transmission dynamics among men who have sex with men (MSM) in bathhouses is constructed and analyzed. The model incorporates key features affecting transmission, including sexual role behavior (insertive and...

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We present a novel hypothesis that could explain virological failure to structured treatment interruptions (STI). We analysed a classic mathematical model of HIV within-host viral dynamics and found that non-linear parametric resonance occurs when STI are added to the model; resonance is observed as virological failure. We simulated clinical trial...

We agree with the thesis of Rosen et al. that despite initiatives such as the World Health Organizations "3 by 5" program rationing of HIV/AIDS antiretroviral therapy (ART) will be necessary in the majority of African countries. Difficult choices will need to be made and choices will be constrained due to the limited health infrastructure and lack...

Background: Approximately 40% of adults in Botswana are HIV-infected. The Botswana antiretroviral program began in 2002 and currently treats 34,000 patients with a goal of treating 85,000 patients (~30% of HIV-infected adults) by 2009. We predict the evolution of drug-resistant strains of HIV that may emerge as a consequence of this treatment progr...

We introduce a class of growing network models that are directly applicable to epidemiology. We show how to construct a growing network model (individual-level model) that generates the same epidemic-level outcomes as a population-level ordinary differential equation (ODE) model. For concreteness, we analyze the susceptible-infected (SI) ODE model...

Current HIV vaccines in development appear unlikely to prevent infection, but could provide benefits by increasing survival; such vaccines are described as disease-modifying vaccines. We review the current status of vaccines and modeling vaccines. We also predict the impact that disease-modifying vaccines could have in South Africa, where multiple...

Pilot studies of structured treatment interruptions (STI) in HIV therapy have shown that patients can maintain low viral loads whilst benefiting from reduced treatment toxicity. However, a recent STI clinical trial reported a high degree of virologic failure. Here we present a novel hypothesis that could explain virologic failure to STI and provide...

The seroprevalence of herpes simplex virus (HSV) type 2 in the United States has increased dramatically since the 1970s. Vaccines are being developed to control the epidemic. We determined the potential public health impact that imperfect, preexposure HSV-2 vaccines could have on reducing the incidence of infection. We modeled the future impact of...

The following questions were addressed: would the introduction of vaginal microbicides substantially reduce the risk of female sex workers (FSWs) acquiring HIV? Which factor would it be most important to maximize, microbicide efficacy or microbicide use? What level of microbicide efficacy and use would be necessary to counterbalance a possible redu...

In many chronic conditions, subjects alternate between an active and an inactive state, and sojourns into the active state may involve multiple lesions, infections, or other recurrences with different times of onset and resolution. We present a biologically interpretable model of such chronic recurrent conditions based on a queueing process. The mo...

Recently, a global commitment has been made to expand access to antiretrovirals (ARVs) in the developing world. However, in many resource-constrained countries the number of individuals infected with HIV in need of treatment will far exceed the supply of ARVs, and only a limited number of health-care facilities (HCFs) will be available for ARV dist...

The U.S. Government has pledged to spend $15 billion in Africa and the Caribbean on AIDS. A central focus of this plan is to provide antiretroviral treatment (ART) to millions. Here, we evaluate whether the plan to rollout ART in Africa is likely to generate an epidemic of drug-resistant strains of HIV. We review what has occurred as a result of hi...

Herpes simplex virus type 2 (HSV-2) is the most prevalent sexually transmitted pathogen worldwide. There is considerable biological and epidemiological evidence that HSV-2 infection increases the risk of acquiring HIV infection and may also increase the risk of transmitting HIV. Here, we use a mathematical model to predict the effect of a high-prev...

Classic modeling of sexually transmitted diseases has focused on modeling behavioral heterogeneity and designing epidemic control strategies targeted at behavioral core groups. We analyzed a new mathematical model of herpes simplex virus type 2 (HSV-2) epidemics that includes virological core groups (i.e., groups of individuals with high rates of v...