Impact of an effective multidrug-resistant tuberculosis control programme in the setting of an immature HIV epidemic: system dynamics simulation model

This study sought to determine the impact of an effective programme of multidrug resistant tuberculosis control (MDRTB) on a population that is witnessing an explosive HIV epidemic among injecting drug users (IDUs), where the prevalence of MDRTB is already high. A transmission model was constructed that represents the dynamics of the drug-susceptible tuberculosis (DSTB), MDRTB and HIV spread among the adult population of Samara Oblast, Russia: from official notifications of tuberculosis and of HIV infection, estimates of MDRTB derived from surveillance studies, population data from official regional statistics, data on transmission probabilities from peer-reviewed publications and informed estimates, and policy-makers' estimates of IDU populations. Two scenarios of programme effectiveness for MDRTB were modelled and run over a period of 10 years to predict cumulative deaths. In a population of 3.3 million with a high prevalence of MDRTB, an emerging epidemic of HIV among IDUs, and a functioning directly observed therapy-short course (DOTS) programme, the model predicts that under low cure rates for MDRTB the expected cumulative deaths from tuberculosis will reach 6303 deaths including 1900 deaths from MDRTB at 10 years. Under high cure rate for MDRTB 4465 deaths will occur including 134 deaths from MDRTB. At 10 years there is little impact on HIV-infected populations from the MDRTB epidemic, but as the HIV epidemic matures the impact becomes substantial. When the model is extended to 20 years cumulative deaths from MDRTB become very high if cure rates for MDRTB are low and cumulative deaths in the HIV-infected population, likewise, are profoundly affected. In the presence of an immature HIV epidemic failure to actively control MDRTB may result in approximately a third more deaths than if effective treatment is given. As the HIV epidemic matures then the impact of MDRTB grows substantially if MDRTB control strategies are ineffective. The epidemiological starting point for these scenarios is present in many regions within the former Soviet Union and this analysis suggests control of MDRTB should be an urgent priority.

[1]  P E Fine,et al.  Interpreting the decline in tuberculosis: the role of secular trends in effective contact. , 1999, International journal of epidemiology.

[2]  T. Frieden,et al.  Controlling multidrug-resistant tuberculosis and access to expensive drugs: a rational framework. , 2002, Bulletin of the World Health Organization.

[3]  Y. Balabanova,et al.  Rifampin- and Multidrug-Resistant Tuberculosis in Russian Civilians and Prison Inmates: Dominance of the Beijing Strain Family , 2002, Emerging infectious diseases.

[4]  Brian Dangerfield,et al.  Optimisation as a statistical estimation tool: an example in estimating the AIDS treatment‐free incubation period distribution , 1999 .

[5]  J. Forrester Industrial Dynamics , 1997 .

[6]  D Alland,et al.  Transmission of tuberculosis in New York City. An analysis by DNA fingerprinting and conventional epidemiologic methods. , 1994, The New England journal of medicine.

[7]  R. May,et al.  The transmission dynamics of human immunodeficiency virus (HIV). , 1988, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[8]  Sonya S. Shin,et al.  The dilemma of MDR-TB in the global era. , 1998, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[9]  Christopher Dye,et al.  Prospects for worldwide tuberculosis control under the WHO DOTS strategy , 1998, The Lancet.

[10]  G W Comstock,et al.  The prognosis of a positive tuberculin reaction in childhood and adolescence. , 1974, American journal of epidemiology.

[11]  J. Gerberding,et al.  Understanding, predicting and controlling the emergence of drug-resistant tuberculosis: a theoretical framework , 1998, Journal of Molecular Medicine.

[12]  D. Alland,et al.  Improved outcomes for patients with multidrug-resistant tuberculosis. , 1995, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[13]  R. Coker Should tuberculosis programmes invest in second-line treatments for multidrug-resistant tuberculosis (MDR-TB)? , 2002, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[14]  Matthew Hickman,et al.  Explosive spread and high prevalence of HIV infection among injecting drug users in Togliatti City, Russia , 2002, AIDS.

[15]  George P. Richardson,et al.  Loop polarity, loop dominance, and the concept of dominant polarity (1984) , 1995 .

[16]  R. Coker,et al.  Tuberculosis transmission and the impact of intervention on the incidence of infection. , 2002, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[17]  E. Nardell,et al.  Molecular epidemiology of tuberculosis: achievements and challenges to current knowledge. , 2002, Bulletin of the World Health Organization.

[18]  R. Coker,et al.  Review: Multidrug‐resistant tuberculosis: public health challenges , 2004, Tropical medicine & international health : TM & IH.

[19]  S. Blower,et al.  Control Strategies for Tuberculosis Epidemics: New Models for Old Problems , 1996, Science.

[20]  H. H. Richardson,et al.  Introduction to system dynamics , 1967 .

[21]  W. Hall,et al.  A mathematical model of HIV transmission in NSW prisons. , 1998, Drug and alcohol dependence.

[22]  C. Murray,et al.  Modeling the impact of global tuberculosis control strategies. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[23]  M. Espinal,et al.  Should tuberculosis programmes invest in second-line treatments for multidrug-resistant tuberculosis (MDR-TB)? , 2001, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[24]  G. Schoolnik,et al.  The epidemiology of tuberculosis in San Francisco. A population-based study using conventional and molecular methods. , 1994, The New England journal of medicine.

[25]  P. Hopewell,et al.  The results of 9-month isoniazid-rifampin therapy for pulmonary tuberculosis under program conditions in San Francisco. , 1988, The American review of respiratory disease.

[26]  Jr Young Tuberculosis: Case Finding and Chemotherapy: Questions and Answers , 1981 .

[27]  P E Fine,et al.  Lifetime risks, incubation period, and serial interval of tuberculosis. , 2000, American journal of epidemiology.

[28]  Tuberculosis in a rural population of South India: a five-year epidemiological study. , 1974, Bulletin of the World Health Organization.

[29]  Nicholas C. Grassly,et al.  Modelling emerging HIV epidemics: the role of injecting drug use and sexual transmission in the Russian Federation, China and India , 2003 .

[30]  B G Williams,et al.  Criteria for the control of drug-resistant tuberculosis. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[31]  A. Wallgren The time-table of tuberculosis. , 1948, Tubercle.

[32]  Brian G. Williams,et al.  Erasing the World's Slow Stain: Strategies to Beat Multidrug-Resistant Tuberculosis , 2002, Science.

[33]  C. Dye,et al.  Feasibility and cost-effectiveness of standardised second-line drug treatment for chronic tuberculosis patients: a national cohort study in Peru , 2002, The Lancet.

[34]  Donna Neuberg,et al.  Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru. , 2003, The New England journal of medicine.

[35]  David N. Ford A behavioral approach to feedback loop dominance analysis , 1999 .

[36]  P. Sonnenberg,et al.  HIV-1 and recurrence, relapse, and reinfection of tuberculosis after cure: a cohort study in South African mineworkers , 2001, The Lancet.

[37]  P. Kvale,et al.  Respiratory disease trends in the Pulmonary Complications of HIV Infection Study cohort. Pulmonary Complications of HIV Infection Study Group. , 1997, American journal of respiratory and critical care medicine.

[38]  R. Atun,et al.  Tuberculosis control in Samara Oblast, Russia: institutional and regulatory environment. , 2003, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[39]  Valerie Isham,et al.  Models for Infectious Human Diseases: Their Structure and Relation to Data , 1996 .

[40]  L. Karasulu,et al.  The treatment of multidrug-resistant tuberculosis in Turkey. , 2001, The New England journal of medicine.

[41]  S. Blower,et al.  Amplification Dynamics: Predicting the Effect of HIV on Tuberculosis Outbreaks , 2001, Journal of acquired immune deficiency syndromes.

[42]  B. Dangerfield,et al.  Model-based scenarios for the epidemiology of HIV/AIDS: the consequences of highly active antiretroviral therapy , 2001 .

[43]  C. Dye,et al.  The resurgence of tuberculosis in Russia. , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[44]  Timothy R Sterling,et al.  Impact of DOTS compared with DOTS-plus on multidrug resistant tuberculosis and tuberculosis deaths: decision analysis , 2003, BMJ : British Medical Journal.

[45]  K. McAdam,et al.  The effect of human immunodeficiency virus type-1 on the infectiousness of tuberculosis. , 1994, Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[46]  C. Guérin,et al.  Treatment of Pulmonary Tuberculosis with Isoniazid , 1952 .

[47]  Steffen Bayer,et al.  Business dynamics: Systems thinking and modeling for a complex world , 2004 .

[48]  H. Rieder,et al.  Epidemiologic basis of tuberculosis control , 1999 .