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Final Report Summary - TECOARTE (Epidemiology and control of tuberculosis in the antiretroviral therapy era: towards a mathematical model for Cape Town, South Africa)

The resurgence of tuberculosis (TB) has been underway for almost 20 years, and despite increasingly implemented comprehensive control strategies, the epidemic in sub-Saharan Africa is continuing to expand. There is an urgent need to elucidate the reasons underlying the failing of TB control and to develop innovative public health approaches.

This project aimed to use a variety of epidemiologic methods to describe the local TB epidemic and its drivers, and to determine the potential impact of different public health interventions in Cape Town, South Africa. State-of-the-art statistical techniques would be used to perform an in-depth analysis of all TB cases in Cape Town in the last decade. These results were to be used to develop and validate a mathematical model of the local TB epidemic, and projections of this model would then be used to estimate the future impact of new and redesigned public health strategies for TB control. In addition, the fellowship would provide an opportunity for me, the researcher, to expand my epidemiological and statistical skills, to broaden my expertise in TB and HIV co-infection research, to gain experience in multidisciplinary collaborations including with regional health authorities and to further develop my transferable skills.

The project has been completed. The outgoing phase consisted of 2 years at the Desmond Tutu HIV Centre at the University of Cape Town in South Africa. The return phase consisted of 1 year at the Amsterdam Institute for Global Health and Development at the University of Amsterdam, the Netherlands. Below is an overview of the work performed, the results and achievements during these 3 years.

All data required were successfully collected and almost all analyses were completed. The mathematical model of TB in Cape Town was developed and validated. These achievements have led to a total of eight presentations of the results at international conferences (for an example, see Figure 1), two presentations at local or regional meetings and five publications in peer-reviewed journals. An additional eight publications emanated from a supervisory or collaboratory role of the postdoctoral researcher. Three manuscripts are still in the process of write-up or peer review.

My research found that the trajectory of TB incidence in Cape Town over the last 100 years, compared to London and New York, has been very different. The introduction of chemotherapy did not reduce the TB epidemic in Cape Town. In addition, even before the advent of the HIV epidemic, TB rates were already at the level of the beginning of the century (Figure 2). The surge following the HIV epidemic has led to the life-time incidence of TB among the population in Cape Town to further increase over the 25% before HIV.

The most important finding of my research is that the burden of recurrent TB in Cape Town is very high with over 30% of TB patients developing one or more additional episodes over a period of 12 years. The risk of another episode of TB increased greatly with every subsequent episode (Figure 3). Looking further in depth at the last 13 years, our analyses show a reduction in TB rates over the last five years (Figure 4). This reduction may be due to antiretroviral therapy roll-out, however the ecological study design did not allow for attribution of causality. An alternative or complementary explanation may be a decline in empirical treatment rates, which we identified in an evaluation of the impact of the roll-out of a new rapid molecular diagnostic test. We developed an age-stratified mathematical model of TB in Cape Town, which confirmed that the TB burden is determined by the underlying age structure, but that a protective effect of latent infection by previous TB strains as well as rates of progression to active TB disease after a prior episode of TB also play an important role.

There has been excellent progress on the training objectives of the fellowship. I was able to successfully establish myself at my host institute during the outgoing phase which led to a productive 2 years. I developed fruitful collaborations with local stakeholders as well as gained in-depth understanding of the local TB epidemic by working alongside local HIV doctors in the Gugulethu ART clinic. Upon my return to the Netherlands I established myself within the group of epidemiologists and set up collaborations with various local and national institutions.

Throughout the fellowship I was able to hone my technical and analytical skills, in particular my experience in working with large databases, time-series analysis, deterministic record linkage and mathematical modelling. There were ample opportunities to further develop my transferable skills, such as the presentations and publications mentioned above, and grant writing. During the last year of the fellowship I wrote and submitted three funding proposals, of which one was successful (TB Reach, Stop TB Department) and one was awarded a Seal of Excellence by the European Research Council (not funded due to the funding ceiling having been reached).

My teaching involvement during the outgoing phase included formal teaching of primary care practitioners all over South Africa in an online TB/HIV course, day to day mentorship of clinicians at the Gugulethu antiretroviral therapy clinic and mentorship of a number of students. Teaching and mentorship duties increased upon my return to the Netherlands, and included teaching in the BSc Medicine Global Health track and the residents in Internal Medicine and supervision of 6 BSc and PhD students.

I was involved in the Eh!Woza programme, a public engagement project involving disseminating high impact TB research to outstanding high school students from under-privileged areas. I collaborated with the adolescent programme and the staff at the Gugulethu ART clinic to develop a comprehensive programme surrounding the World AIDS Day celebrations in 2015 and 2016 (Figure 4).

Throughout the project we collaborated closely with the Cape Town TB programme. During a dissemination meeting I presented our main findings and discussed plans for future collaborative work into elucidating the mechanisms underlying and interventions to reduce the large burden of recurrent TB. Throughout this process I will continue to collaborate closely with the TB programme, to ensure relevance and uptake of our results into local policy and practice.

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