Review 4: "Strong Effect of Demographic Changes on Tuberculosis Susceptibility in South Africa"

Najwa A. Mhmoud

Strong Effect of Demographic Changes on Tuberculosis Susceptibility in South Africa

by Oshiomah Oyageshio, Justin Myrick, Jamie Saayman, Lena van der Westhuizen, Dana Al-Hindi, Austin W Reynolds, Noah Zaitlen, Caitlin Uren, Marlo Möller, and Brenna Henn

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Published on Nov 04, 2023
www.medrxiv.org

Description

Abstract South Africa is among the world’s top eight TB burden countries, and despite a focus on HIV-TB co-infection, most of the population living with TB are not HIV co-infected. The disease is endemic across the country with 80-90% exposure by adulthood. We investigated epidemiological risk factors for tuberculosis (TB) in the Northern Cape Province, South Africa: an understudied TB endemic region with extreme TB incidence (645/100,000) and the lowest provincial population density. We leveraged the population’s high TB incidence and community transmission to design a case-control study with population-based controls, reflecting similar mechanisms of exposure between the groups. We recruited 1,126 participants with suspected TB from 12 community health clinics, and generated a cohort of 878 individuals (cases =374, controls =504) after implementing our enrollment criteria. All participants were GeneXpert Ultra tested for active TB by a local clinic. We assessed important risk factors for active TB using logistic regression and random forest modeling. Additionally, a subset of individuals were genotyped to determine genome-wide ancestry components. Male gender had the strongest effect on TB risk (OR: 2.87 [95% CI: 2.1-3.8]); smoking and alcohol consumption did not significantly increase TB risk. We identified two interactions: age by socioeconomic status (SES) and birthplace by residence locality on TB risk (OR = 3.05, p = 0.016) – where rural birthplace but town residence was the highest risk category. Finally, participants had a majority Khoe-San ancestry, typically greater than 50%. Epidemiological risk factors for this cohort differ from other global populations. The significant interaction effects reflect rapid changes in SES and mobility over recent generations and strongly impact TB risk in the Northern Cape of South Africa. Our models show that such risk factors combined explain 16% of the variance (r2) in case/control status.

RR:C19 Evidence Scale rating by reviewer:

Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review:

In this manuscript, the main claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision. The following details comments of aspects of the paper:

Title & Abstract

Do the title and abstract cover the main aspect of the work?
The title and abstract are relevant to the study.
Does the introduction provide background and information relevant to the study?
Yes, it provides sufficient information.

Material and Methods

Are the methods clear and replicable? Do all the results presented match the methods described?
Yes, the results are clear.

Results

If relevant, are the results novel? Does the study provide an advance in the field? Is the data plausible?
Result are clear and it is a new finding in South African population

Discussion

Do the findings described by the author correlate with the results? Are the findings relevant?
Yes, there are relevant findings and they correlate with the result.

Conclusion

Do the conclusions correlate to the results found?
Yes, there are relevant findings and they correlate with the result.

Figures & Tables

If the author has provided figures and tables are the figures and tables clear and legible? Are the figures free from unnecessary modification?
Authors make clear tables - it is understandable.

Review 4: "Strong Effect of Demographic Changes on Tuberculosis Susceptibility in South Africa"

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