eTable 1. Summary of included studies listed by WHO region.

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eTable 1. Summary of included studies listed by WHO region.

Author & date Study location Study period

Data source Sample size

Event studied Seasonal amplitude African Region (AFR)

Shennan, 1993 [42]

Ciskei (now in South Africa)

1988-1991 National TB register

5,783 Registration of sputum-smear positive PTB

26.2%

Schaaf et al.,

1996 [57] Western Cape Province, South Africa

1983-1993 Tertiary

hospital 1,204 Presentation (submission date of first positive culture) of culture-positive TB in children (<13yo)

30.6%

Ane-Anyangwe et al., 2006 [59]

Fako district, Cameroon

2002-2004 Hospital (level not specified)

652 Diagnosis of sputum-smear positive PTB

-

Desalu, 2011 [74]

Nigeria 2006-2009 Tertiary hospital

68 Hospitalization due to PTB -

Martineau et al., 2011 [9]

Cape Town, South Africa

2005-2010 Local TB register

~150,995 Notification of TB 9.1%

Visser et al., 2013 [63]

Cape Town, South Africa

2000-2005 Tertiary hospital

189 Hospitalization of lab- or clinically-confirmed tuberculous meningitis in children (<13yo)

-

Dangor et al., 2014 [17]

Soweto, South Africa

2005-2008 Hospital (level not specified)

667 Hospitalization of culture- positive PTB in children (<15yo)

-

Burke et al.,

2014 [75] Zimbabwe 1995-2012 Hospital (rural mission hospitals)

16,784 Diagnosis of radiologically or laboratory confirmed sputum- smear positive TB

-

Liu et al., 2015 [24]

Dar es Salaam, Tanzania

2004-2012 Prospective cohort study

7,602 Diagnosis of sputum-smear positive or radiologically confirmed TB or prescription of anti-TB medication during follow-up among HIV positive adults (>14 years old)

-

Walaza et al., 2015 [18]

South Africa 1999-2009 National mortality register

63,596 Deaths related to PTB -

Ade et al., 2016 [62]

Benin 2000-2014 National TB

register

54,303 Notification of

bacteriologically or clinically confirmed TB

2.7%

Azeez et al.,

2016 [56] Eastern Cape,

South Africa 2010-2015 Local TB

register ~430,500 Notification of laboratory confirmed sputum-smear positive PTB

16.3%

Region of the Americas (AMR) Chen et al., 2012

[46]

USA 2000-2010 National TB

register

~136,400 Notification of laboratory- confirmed or clinically diagnosed TB cases

33.6%

Parrinello et al., 2012 [22]

New York City, USA

31,071 Notification of laboratory or clinically diagnosed TB

10.2%

Willis et al.,

2012 [14] USA 1993-2008 National TB

register 243,432 Notification of sputum-smear positive or culture-positive TB

-

Wingfield et al., 2014 [4]

Ventanilla (northern Lima), Peru

2003-2006 Cohort study of TB

determinants

852 Diagnosis of sputum-smear positive or culture-positive PTB in adults (>16 years old)

-

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Eastern Mediterranean Region (EMR) Akhtar and

Mohammad, 2008 [51]

Kuwait 1997-2006 National TB

register 4,608 Diagnosis of sputum-smear and culture-positive PTB among migrant workers

18.6%

Rafei et al., 2012 [76]

Iran 2005-2011 National TB

register

29,186 Notification of sputum-smear positive PTB

-

Moosazadeh et al., 2013 [48]

Mazandaran Province, Iran

3,313 Diagnosis of TB 20.8%

Moosazadeh et al., 2014 [50]

Iran 2005-2011 National TB

register

10,587 Notification of TB among migrants

13.3%

Khaliq et al., 2015 [77]

Lahore, Pakistan 2006-2013 DOTS register 55,636 Registration to DOTS of sputum-smear positive PTB patients

22.0%

Moosazadeh et

al., 2015 [23] Iran 2005-2012 National TB

register 34,012 Notification of sputum-smear

positive PTB 15.0%

Margalit et al., 2016 [66]

Israel 2001-2011 National TB register

2,653 Notification of culture- positive or sputum-smear positive TB

10.2%

European Region (EUR) Douglas et al.,

1996 [3]

England and Wales, UK

57,713 Notification of TB 12.4%

Douglas et al., 1998 [12]

England, Wales and Scotland, UK

Ríos et al., 2000 [78]

Spain 1971-1996 National TB

register

~238,862 Notification of PTB -

Atun et al., 2005 [40]

Samara region, Russia

~1,800 Notification of TB -

Ustianowski et al., 2005 [13]

London, UK 1998-2001 Hospital (infectious disease unit)

207 Diagnosis of TB and commencement of anti-TB treatment among patients with recorded plasma 25(OH)D3

level

-

Luquero et al., 2008 [44]

Spain 1996-2004 National TB

register

71,553 Notification of PTB -

Koh et al., 2012

[11] Birmingham,

UK 1981-2009 National TB

register 9,739 Notification of TB in adults

(>16 years old) 10.5%

Korthals Altes et al., 2012 [10]

Netherlands 1993-2008 National TB register

12,830 Presentation of culture- positive TB (submission date of first positive culture)

29.2%

Soetens et al., 2013 [35]

Netherlands 1993-2004 National TB register

4,746 Notification of culture- positive TB, limited to clustered cases with known TB localization

25.7%

Top et al., 2013

[16] Netherlands 1993-2008 National TB

register 9,979 Notification of culture- positive TB, limited to cases with known TB localization, clustered status, and either PTB or EPTB

24.5%

Bras et al., 2014 [64]

Portugal 2000-2010 National TB register

28,615 Notification of PTB -

Padberg et al., 2015 [15]

Germany 2001-2012 National TB register

4,021 Notification of TB -

Álvaro-Meca et al., 2016 [20]

Spain 1997-2012 Hospital (all public hospitals)

5,712 (First) hospitalization among HIV+ adults (>16 years old) with a PTB diagnosis

13.3%

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South-East Asia Region (SEAR) Thorpe et al.,

2004 [58] India 1996-2001 National TB

register 11,101 Diagnosis of TB 12.7%

Behera and Sharma, 2011 [52]

Delhi, India 2002-2008 Tertiary hospital

28,161 Diagnosis of TB 21.5%

Kumar et al., 2014 [53]

Delhi, India 2007-2012 DOTS register 417 Presentation of sputum-smear positive PTB (submission date of first positive smear)

85.5%

Narula et al., 2015 [28]

India 2006-2011 National TB

register

~5,300,000 Notification of sputum-smear positive TB

9.6%

Western Pacific Region (WPR) Leung et al.,

2005 [54]

Hong Kong 1991-2002 Local TB register

Yang et al., 2008 [43]

Sichuan Province, China

445,557 Notification of laboratory or clinically confirmed PTB

42.9%

Naranbat et al., 2009 [29]

Mongolia 1998-2006 National TB register

14,905 Notification of sputum-smear positive PTB

43.4%

Liao et al., 2012 [27]

Taiwan 2004-2008 Local TB

register

~74,903 Notification of TB 17.1%

MacLachlan et al., 2012 [55]

Australia 2002-2011 National TB register

Cao et al., 2013 [47]

China 2005-2011 National TB

register

10,233,022 Notification of laboratory or clinically confirmed TB

19.4%

Li et al., 2013 [2]

China 2005-2012 National TB

register

7,780,000 Notification of TB -

Zhang et al., 2013 [79]

Hubei, China 2004-2011 Local TB register

465,960 Notification of TB -

Luo et al., 2014 [19]

Wuhan, China 2006-2010 Local TB register

35,875 Notification of PTB 24.9%

Yang et al., 2014 [21]

Wuhan, China 2004-2013 National TB register

-

Wah et al., 2014 [41]

Singapore 1995-2011 National TB register

40,046 Notification of culture- positive TB

-

Onozuka and Hagihara, 2015 [61]

Fukouka, Japan 2008-2012 National TB register

5,904 Diagnosis of laboratory or clinically confirmed TB

-

Kohei et al., 2016 [65]

Japan 1998-2013 National TB

register

470,590 Notification of laboratory or clinically confirmed TB

-

Rao et al., 2016 [26]

Qinghai Province, China

25.5%

Yang et al., 2016 [49]

Shaanxi Province, China

273,305 Notification of PTB 32.1%

You et al., 2016

[45] Beijing and

Hong Kong, China

2012-2014 Local TB

register ~38,200 Notification of laboratory or

clinically confirmed TB 18.2%

Ge et al., 2016 [80]

Zhejiang Province, China

147,941 Diagnosis of TB -

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eFigure A. Normalized seasonal amplitude is half the peak observed value (for a given time period) minus trough observed value as a

percent of the mean observed value. Unweighted regression with quadratic latitude term is shown with 95% confidence interval. For

studies reporting results at the regional or national level, the mean latitude was applied. 95% confidence intervals for both linear and

quadratic regression coefficients include zero.

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eFigure B. Normalized seasonal amplitude of diagnoses/notifications with respect to seasonal forcing in transmission or reactivation at varying levels of baseline annual incidence. Seasonal forcing is implemented with the formula x

_t

= x

₀

α^cos(2 (t/12)) where x

_t

is the rate at month t, x

₀

is the baseline parameter and α is the seasonal multiplier depicted in the figure. Baseline incidence was varied by scaling the transmission rate β by a constant; the y-axis shown in this figure represents constants of 1 to 10 in increments of 0.25.

Over the range shown, baseline annual incidence scales exponentially with this constant.

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eFigure C. Heatmap displaying month of notification peak with normalized seasonal amplitude (color scale and exact value in

parentheses) with respect to changes in average diagnosis delay and length of early disease compared to baseline. Seasonal

multipliers for reactivation, transmission and primary progressive rate are set at 1.3 in this simulation in order to recreate the

weighted observed seasonal amplitude average of 17%. Rates x for month t are determined by the equation x

_t

= x

₀

α^cos(2 (t/12))

where x

₀

is the baseline parameter and α is the seasonal multiplier. Base case is noted with gray outline.

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Additional References

74. Desalu OO. Seasonal variation in hospitalisation for respiratory diseases in the tropical rain forest of South Western Nigeria. Niger Postgrad Med J. 2011;18(1):39–43.

75. Burke SJ, Lass E, Thistle P, Katumbe L, Jetha A, Schwarz D, et al. Increased incidence of tuberculosis in Zimbabwe, in association with food insecurity, and economic collapse: An ecological analysis. PLoS One. 2014;9(2).

76. Rafei A, Pasha E, Orak RJ. Tuberculosis Surveillance Using a Hidden Markov Model.

2012;41(10):87–96.

77. Khaliq A, Batool SA, Chaudhry MN. Seasonality and trend analysis of tuberculosis in Lahore, Pakistan from 2006 to 2013. J Epidemiol Glob Health. 2015;5(4):397–403.

78. Ríos M, García JM, Sánchez JA, Pérez D. A statistical analysis of the seasonality in pulmonary tuberculosis. Eur J Epidemiol. 2000;16(5):483–8.

79. Zhang G, Huang S, Duan Q, Shu W, Hou Y, Zhu S, et al. Application of a hybrid model for predicting the incidence of tuberculosis in Hubei, China. PLoS One. 2013;8(11):1–7.

eTable 1. Summary of included studies listed by WHO region.