Behind the paper: Striving for zero TB-related mortality in Zambia

In this post, we talk to the authors of Mortality among persons with tuberculosis in Zambian hospitals: A retrospective cohort study, which was recently published in PLOS Global Public Health. The authors of this paper are Josphat Bwembya, Ramya Kumar, Victoria Musonda, Rhehab Chimzizi, Nancy Kasese-Chanda, Lameck Goma, Mushota Kabaso, Reford Mihova, Sulani Nyimbili, Vimbai Makwambeni, Soka Nyirenda, Alwyn Mwinga, and Patrick Lungu.

What led you to decide on this research question?

This research was motivated by the Zambian National Strategic Plan’s goal of zero mortality, aiming to identify factors related to TB death and design targeted interventions to reduce TB-related mortality. The TB program leveraged an operational research training program developed in Zambia, which trained district health workers to design studies using routine TB data, with details published in Public Health Action, and  highlighted by the University of Washington. A significant output from this program was a mortality review in rural Itezhi-tezhi district, published in PLOS Global Public Health last year. The national TB program noted the alarming findings on deaths among people on TB treatment, and leveraged local research teams for a comprehensive mortality review in over 50 facilities nationwide. This initiative demonstrates how small-scale operational research studies that use routine data for local solutions can contribute to national initiatives to end the TB epidemic.

Could you talk us through how you designed your study? What was important for your team as you created the study team?

This is the first nationwide TB mortality review ever undertaken in Zambia, so our study was designed through a collaborative effort between the national TB Program and partners like the USAID Eradicate TB Project, which provided research and programmatic expertise. Our primary focus was to ensure high-quality data, and rigorous methodology to produce reliable results for informing the TB program.

We assembled a multidisciplinary team of TB specialists, epidemiologists, clinicians, and data analysts to design and conduct the study. Regular consultations and ongoing training were conducted to ensure data accuracy and consistency. The collaboration between the USAID Eradicate TB Project’s research expertise and the national TB Program’s operational knowledge was essential for effectively addressing TB mortality and treatment outcomes.

What challenges did you encounter during your study?

The greatest challenge was also the greatest strength of our study — the large sample size drawn from all 10 provinces of Zambia. This was an immense undertaking. The teams reviewed not only TB registers but also medical files, including death certificates for those who died. This enabled us to collect data on comorbidities and probable causes of death that are not routinely captured in TB registers. This would not have been possible without nationwide data collectors who volunteered their time. 

What did you find most striking about your results? How will this research be used?

The most striking finding from our research was that more than half (58.1%) of the 1,063 deaths recorded during the 12 months occurred within the first month of TB treatment, and 75.1% occurred within the first two months. The median time to death was just 21 days (IQR: 6–57). Additionally, a significant proportion of deaths were due to disseminated TB/TB sepsis with or without end-organ damage indicative of a widespread infection that significantly complicates treatment and increases the risk of mortality.  This finding is important because it highlights the severity and systemic spread of TB, indicating that many patients are experiencing advanced stages of the disease by the time they receive treatment.  Taken together, this implies a late diagnosis of TB.

Moreover, the approach to TB management in Zambia is not tailored to different types of TB. Most patients receive the four fixed-dose combination (4FDC) regardless of the extent of their disease. While 4FDC simplifies the treatment regimen by combining four essential anti-TB drugs into a single pill, this uniform approach fails to address the specific needs and conditions of individual patients. Furthermore, frontline health care workers often lack the necessary skills to recognize TB sepsis and disseminated TB.

Contributing to this issue are delayed diagnoses, unconventional health-seeking behaviors, and a low index of suspicion, especially for extrapulmonary TB (EPTB). This alarming concentration of early deaths underscores the critical need for immediate and enhanced interventions at the initiation of TB treatment. Our research will be used to inform the national TB program’s strategies, emphasizing the importance of early support and intensive care during the initial phase of treatment. It highlights the urgent need for targeted measures to reduce mortality rates and improve patient outcomes in the critical first months of TB treatment.

What further research questions need to be addressed in this area?

This study found that early death during TB treatment could be attributed to people not being able to report their symptoms to the health facility earlier. However, our study did not collect information that would have helped us to confirm this claim. Also, we did not capture information on the time between diagnosis and treatment initiation. Future studies should assess the relationship between mortality, the time to TB symptom reporting, and time to treatment initiation. There is also a need for further research into how social and economic factors (such as nutritional status) influence TB mortality in Zambia.

Why did you choose PLOS Global Public Health as a venue for your article?

We chose PLOS Global Public Health for our article due to its equitable pricing for LMICs and its respected status as a global Open Access forum for public health research. The journal’s commitment to addressing major health challenges and its equity, diversity, and inclusion core values align with our goals. The journal’s engagement with diverse voices through various formats made it the ideal platform for our research. Ramya has written for the Speaking of Medicine blog, served as a reviewer, and has built a rapport with the Editors-in-Chief.

Disclaimer: Views expressed by contributors are solely those of individual contributors, and not necessarily those of PLOS.

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