Control Strategies for Tuberculosis Epidemics: New Models for Old Problems

Blower, Sally; Small, Peter M.; Hopewell, Philip C.

doi:10.1126/science.273.5274.497

Cited by 287 publications

(200 citation statements)

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“…Mathematical models have been used to project the effect of treating latent TB infections in populations with (22,(33)(34)(35)(36)(37) and without concurrent HIV epidemics (19,38). We have extended these models to evaluate the potential impact of programs for community-wide IPT on the dynamics of drug-resistant TB.…”

Section: Discussionmentioning

confidence: 99%

“…To assess the impact of community-wide IPT on the dynamics of drug-resistant TB, we constructed a simple deterministic model of TB transmission based on a structure previously developed for the evaluation of control policies (19)(20)(21)(22)(23). The TB infection process was linked to a dynamic model of HIV transmission, and the model thus included interacting subpopulations of HIV-infected and noninfected individuals.…”

Section: Modelmentioning

confidence: 99%

See 1 more Smart Citation

Beneficial and perverse effects of isoniazid preventive therapy for latent tuberculosis infection in HIV–tuberculosis coinfected populations

Cohen

Lipsitch

Walensky

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

108

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In sub-Saharan Africa, where the emergence of HIV has caused dramatic increases in tuberculosis (TB) case notifications, new strategies for TB control are necessary. Isoniazid preventive therapy (IPT) for HIV-TB coinfected individuals reduces the reactivation of latent Mycobacterium tuberculosis infections and is being evaluated as a potential community-wide strategy for improving TB control. We developed a mathematical model of TB͞HIV coepidemics to examine the impact of community-wide implementation of IPT for TB-HIV coinfected individuals on the dynamics of drugsensitive and -resistant TB epidemics. We found that communitywide IPT will reduce the incidence of TB in the short-term but may also speed the emergence of drug-resistant TB. We conclude that community-wide IPT in areas of emerging HIV and drug-resistant TB should be coupled with diagnostic and treatment policies designed to identify and effectively treat the increasing proportion of patients with drug-resistant TB.mathematical model ͉ AIDS ͉ prophylaxis T uberculosis (TB) incidence and mortality in sub-Saharan Africa have reached alarming levels and continue to rise. TB control in this region has been hindered by the emergence of HIV (1); in areas most affected, annual TB case notifications have quadrupled over the past 15 years (2). In August 2005, 46 regional Ministers of Health declared that the TB epidemic is an emergency in Africa.HIV significantly affects the progression of Mycobacterium tuberculosis infection. Whereas M. tuberculosis infection in immunocompetent hosts usually results in latent nontransmissible infection, individuals coinfected with HIV͞TB are at high risk of progressing from latent infection to active TB. Because of this interaction, most public health authorities have concluded that the World Health Organization's Stop TB Strategy will fail to curb the epidemic in areas where HIV is prevalent. This strategy emphasizes the rapid diagnosis of TB and the reliable availability and administration of antibiotics to those affected. Although this approach has been successful in areas of low HIV prevalence, additional measures are necessary to reduce TB incidence in high HIV-burden regions (3).To identify such measures, investigators are conducting several large studies of the community impact of preventive therapy to interrupt progression from latent infection to active TB among HIV-TB coinfected individuals. This strategy, called isoniazid (INH) preventive therapy (IPT), uses INH monodrug therapy for coinfected patients. Clinical trials in the 1950s showed that IPT reduced the incidence of active TB in immunocompetent individuals infected with M. tuberculosis (4); more recent studies have also demonstrated its efficacy among HIV-TB coinfected individuals (5-7). The World Health Organization currently recommends that HIV͞AIDS programs include IPT as part of their package of care for the HIV infected.Despite evidence that IPT reduces TB incidence among HIV-TB coinfected individuals, it is not clear that communitywide IPT will prove ef...

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Section: Discussionmentioning

confidence: 99%

Section: Modelmentioning

confidence: 99%

Beneficial and perverse effects of isoniazid preventive therapy for latent tuberculosis infection in HIV–tuberculosis coinfected populations

Cohen

Lipsitch

Walensky

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

108

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“…We developed an age-structured mathematical model similar to previous TB models (11)(12)(13)(14) described by a series of differential equations (Fig. 1, SI Appendix, and SI Technical Appendix).…”

Section: Methodsmentioning

confidence: 99%

“…Although other groups have modeled potential effects of new technologies (7)(8)(9)(10), none has specifically assessed and compared the benefits of the vaccines, drug regimens, and diagnostics under development. Here, we report on research using a mathematical model of TB transmission based on previous TB models (11)(12)(13)(14) to investigate potential epidemiological benefits of the novel interventions (Fig. 1).…”

mentioning

confidence: 99%

Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics

Abu‐Raddad

Sabatelli

Achterberg

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

324

303

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The Bill and Melinda Gates Foundation supports an ambitious portfolio of novel vaccines, drug regimens, and diagnostic tools for tuberculosis (TB). We elicited the expected efficacies and improvements of the novel interventions in discussions with the foundations managing their development. Using an age-structured mathematical model of TB, we explored the potential benefits of novel interventions under development and those not yet in the portfolio, focusing on the WHO Southeast Asia region. Neonatal vaccination with the portfolio vaccine decreases TB incidence by 39% to 52% by 2050. Drug regimens that shorten treatment duration and are efficacious against drug-resistant strains reduce incidence by 10 -27%. New diagnostics reduce incidence by 13-42%. A triple combination of a portfolio vaccine, drug regimen, and diagnostics reduces incidence by 71%. A short mass vaccination catch-up campaign, not yet in the portfolio, to augment the triple combination, accelerates the decrease, preventing >30% more cases by 2050 than just the triple combination. New vaccines and drug regimens targeted at the vast reservoir of latently infected people, not in the portfolio, would reduce incidence by 37% and 82%, respectively. The combination of preventive latent therapy and a 2-month drug treatment regimen reduces incidence by 94%. Novel technologies in the pipeline would achieve substantial reductions in TB incidence, but not the Stop TB Partnership target for elimination. Elimination will require new delivery strategies, such as mass vaccination campaigns, and new products targeted at latently infected people. latent infection ͉ novel interventions ͉ transmission model ͉ latent therapy T he Bill and Melinda Gates Foundation (BMGF) supports an ambitious portfolio of novel vaccines, treatment regimens, and diagnostic tools for tuberculosis (TB). Funded by BMFG and other sources, the Aeras Global TB Vaccine Foundation oversees vaccine development (1), the TB Alliance seeks novel drug regimens (2), and the Foundation for Innovative New Diagnostics (FIND) looks for new diagnostic tools (3). The current cornerstone of TB intervention is directly observed short-course therapy (DOTS), lasting generally 6 months and prone to dropout (4). DOTS is currently implemented in the 184 countries where 99% of all estimated TB cases occurred and 93% of the world population lived in 2006 (5). Cases are passively ascertained. Sputum smear light microscopy has been the mainstay of TB diagnosis for more than a century, but has important limitations (3). Delays between the patient visit to the clinic and diagnosis often lead to delays in treatment. Neonatal vaccination with bacillus Calmette-Guérin (BCG) vaccine is part of the expanded program of immunization in many countries, but its efficacy against pulmonary TB is poor (1). Despite these efforts, in large parts of Asia, Africa, Eastern Europe, and Latin America, incidence remains 2 orders of magnitude (5) above the Stop TB Partnership goal to eliminate TB as a public health problem, defined as Ͻ1 ...

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“…Mathematical modeling has proven a valuable tool for understanding TB dynamics (Blower et al, 1995;Vynnycky and Fine, 1997;Feng et al, 2000;Singer and Kirschner, 2004) and has served as the basis for establishing control targets and assessing policy strategies (Blower et al, 1996;Dye et al, 1998;Cohen et al, 2006). However, most such models, with occasional exceptions (Schinazi, 1999), have been differential equation susceptible-exposed-infected-recovered (SEIR) models that assume a homogenously mixed population.…”

Section: Introductionmentioning

confidence: 99%

Emergent heterogeneity in declining tuberculosis epidemics

Colijn

Cohen

Murray

2007

Journal of Theoretical Biology

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Tuberculosis is a disease of global importance: over 2 million deaths are attributed to this infectious disease each year. Even in areas where tuberculosis is in decline, there are sporadic outbreaks which are often attributed either to increased host susceptibility or increased strain transmissibility and virulence. Using two mathematical models, we explore the role of the contact structure of the population, and find that in declining epidemics, localized outbreaks may occur as a result of contact heterogeneity even in the absence of host or strain variability. We discuss the implications of this finding for tuberculosis control in low incidence settings.

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Control Strategies for Tuberculosis Epidemics: New Models for Old Problems

Cited by 287 publications

References 12 publications

Beneficial and perverse effects of isoniazid preventive therapy for latent tuberculosis infection in HIV–tuberculosis coinfected populations

Beneficial and perverse effects of isoniazid preventive therapy for latent tuberculosis infection in HIV–tuberculosis coinfected populations

Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics

Emergent heterogeneity in declining tuberculosis epidemics

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