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Drivers of Seasonal Variation in Tuberculosis Incidence

Insights from a Systematic Review and Mathematical Model

Tedijanto, Christinea; Hermans, Sabineb; Cobelens, Frankb; Wood, Robinc; Andrews, Jason R.d

doi: 10.1097/EDE.0000000000000877
Infectious Diseases

Background: Seasonality in tuberculosis incidence has been widely observed across countries and populations; however, its drivers are poorly understood. We conducted a systematic review of studies reporting seasonal patterns in tuberculosis to identify demographic and ecologic factors associated with timing and magnitude of seasonal variation.

Methods: We identified studies reporting seasonal variation in tuberculosis incidence through PubMed and EMBASE and extracted incidence data and population metadata. We described key factors relating to seasonality and, when data permitted, quantified seasonal variation and its association with metadata. We developed a dynamic tuberculosis natural history and transmission model incorporating seasonal differences in disease progression and/or transmission rates to examine magnitude of variation required to produce observed seasonality in incidence.

Results: Fifty-seven studies met inclusion criteria. In the majority of studies (n=49), tuberculosis incidence peaked in spring or summer and reached a trough in late fall or winter. A standardized seasonal amplitude was calculated for 34 of the studies, resulting in a mean of 17.1% (range: 2.7–85.5%) after weighting by sample size. Across multiple studies, stronger seasonality was associated with younger patients, extrapulmonary disease, and latitudes farther from the Equator. The mathematical model was generally able to reproduce observed levels of seasonal case variation; however, substantial variation in transmission or disease progression risk was required to replicate several extreme values.

Conclusions: We observed seasonal variation in tuberculosis, with consistent peaks occurring in spring, across countries with varying tuberculosis burden. Future research is needed to explore and quantify potential gains from strategically conducting mass screening interventions in the spring.

From the aDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA

bDepartment of Global Health, Academic Medical Center, Amsterdam, North Holland, The Netherlands

cDesmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Western Cape, South Africa

dDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA.

Submitted October 8, 2017; accepted May 31, 2018.

All data was obtained or extracted from published articles, as described in the Methods. Please contact the corresponding author for computing code.

This work was supported by grant K01 AI104411 (to J.R.A.) from the National Institutes of Health.

The authors report no conflicts of interest.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (

Correspondence: Christine Tedijanto, Harvard T.H. Chan School of Public Health, Department of Epidemiology, 677 Huntington Avenue, Suite 506, Boston, MA 02115. E-mail:

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