Tuberculosis Transmission Robin Wood, University of Cape Town, South Africa

Transcription

1 Tuberculosis Transmission Robin Wood, University of Cape Town, South Africa Tuberculosis Pavilion, Riverside Hospital, New York

2 A Century of Tuberculosis Epidemiology in the Northern and Southern Hemisphere: The Differential Impact of Control Interventions Sabine Hermans, C. Robert Horsburgh, Jr., Robin Wood PLoS ONE 2015; 10(8): e doi: /journal.pone Age-stratified TB notification rates per decade over time. Y-axes are on a logarithmic scale (base 10). Age-stratified rates in Cape Town were not available prior to Cape Town rates for 2002 and 2010 include TB in HIV-infected persons.

3 TB Incidence: 20 Highest Burdened Countries South Africa Lesotho DPR Korea Mozambique Namibia Indonesia Zambia CAR Cambodia Congo Angola Myamar DR Congo Phillipines Nigeria Liberia Sierra Leone Tanzania Pakistan Zimbabwe Estimated TB incidence WHO Global TB Report 2016

4 Current Burden of Tuberculosis Cape Town, United States, United Kingdom, France & Canada Annual TB notifications Cases notified per year Cape Town USA UK France Canada Data WHO Global TB Report 2016

5 Cape Town TB Control Measures Edinburgh TB management scheme 1. Dispensary for diagnosis & triage 2. Sanatorium admission for early cases 3. Hospitalization for advanced cases 1997 DOTS. directly observed therapy 1899 City Hospital for Infectious Diseases Mass Radiography Total 3,3 million radiographs 1988 Fixed dose TB combination therapy 1911 Founding of Society for Prevention of Consumption 1959 BCG vaccination for all newborns Compulsory notification of TB cases and deaths 1924 Nelspoort Sanatorium opened by Prince of Wales 1983 Rifampin based short course chemotherapy 2002 Public sector antiretroviral therapy 1908 Tuberculin testing of cattle 1952 Mandatory milk pasteurisation 1953 Combination TB therapy Strep/PAS/INH

6 Cape Town, TST+ve Prevalence by Age (TBD-ve) School entry 20% Sexual debut 55% Peak HIV Prevalence 88% N.B By 40yrs>10% have had TB disease 80 Population percentage Age Wood et al IJTLD. 2010; 14(4):

7 Airborne Component of M.tuberculosis Life Cycle Wells & Riley Equation C=S(1-e -iptq/q )

8 Generalised Version of Wells-Riley Equation The Wells-Riley Equation can be modified to model the transmission of MTB, spread within a given population Force of infection C/S = 1-e -(ftp*tbi*δ*βθdf) f *t*p is the volume of air breathed from others. f is fraction of air breathed from others t is time p is breathing rate tbi*δ is the population prevalence of infectious cases tbi is TB incidence rate Δ is the period of infectiousness β*θ*df is the infectivity of prevalent TB cases β is respirable TB organisms per exhaled volume θ is the organism survival function df is the deposition fraction in alveoli

9 Annual Risk of TB Infection is Determined by Number of Inhaled TB Infectious Quanta per Year Annual Risk of TB Infection P inf = 1-e -(ftp*tbi*δ*βθdf) Generalised version of Wells & Riley Equation C=S(1-e -iptq/q ) Volume of shared air f*t*p Prevalence of TB cases TBI*Δ Infectious quanta concentration Β*θ*δf Social mixing & environment TB control programme TB case infectiousness

10 Modeling the risk of airborne infectious disease using exhaled air Total amount of rebreathed air inhaled from others is proportional to C (T) the area under the curve between times T A and T D corrected for number of people in the room (n-1/n) V= room volume, Q= ventilation, C a = CO 2 production rate Issarowa CM, Mulder N, Wood R. Journal of Theoretical Biology 372 (2015)

11 Continuous Personal CO 2 Monitor & GPS GPS Antenna USB interface CO 2, RH and Temp Monitor (CoZIR) Thermostat Power Supply

12 Variable Positioning of the Personal CO 2 Monitor Y = CO 2 levels ppm, X = time Monitor Positions: Forehead, Throat, Room, Chest, Lanyard and Waist

13 TB conference attendees 70 liters of shared air Net CO 2 (ppm) Time

14 An Adolescent s Day at School

15 C 2 D H G F A B E C Rebreathed litres per minute A B C A 1 D E F G C 2 H 8:00 8:30 9:00 9:30 10:00 10:30 11:00 11:30 12:00 12:30 13:00 13:30 14:00 14:30 15:00 Time of Day Richardson ET et al. Plos one 2014

16 Total House School Trans Other Total House School Trans Other Figure 4 A: Volumes of rebreathed air recorded in summer months. The figure shows median, inter-quartile ranges and maximum and minimum volumes of rebreathed air from others for 28 weekdays recorded between November and April together with volume contributions from households, school attendance, transport and various other locations. Figure 4 B: Volumes of rebreathed air recorded in winter months. The figure shows weekdays recorded between May and October. volumes of rebreathed air from others for 63

17 Patterson B et al. Science of the Total Environment 583 (2017)

18 GPS locations with rebreathed air volumes of 100 ml/min or greater. Patterson B et al. Science of the Total Environment 583 (2017)

19 Integrating Social Contact and Environmental Data in Evaluating Tuberculosis Transmission in a South African Township Figure 3. Estimated proportion of tuberculosis infections acquired in each setting, according to age group. Abbreviation: HH, household. Jason Andrews et al. JID 2014;210:

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21 Mean CO 2 above atmospheric = 930ppm Maximum = 1350 ppm The Journal of Hygiene, Vol. 22, No. 2 (Jan., 1924), pp

22 Correlation between the mean indoor CO2 concentrations in 62 naturally ventilated classrooms and air flow per person. Red line represents idealized steady-state values. Adapted from M. Santamouris et al. (2008).

23 Recommended ventilation rates in classrooms by country [41 45].

24 Drivers of TB Transmission Air volumes exchanged Social mixing Environmental conditions Prevalence of TB transmitters TB control program removal of prevalent cases Infectiousness of TB transmitters Outbreaks from MTB super-spreaders Endemic TB from spectrum of MTB infectiousness

25 UCT TB Aerobiology Team Desmond Tutu HIV Centre Robin Wood Carl Morrow Melitta Gqada Keren Middelkoop Juane Leukes Morne Smidt Microbiology Digby Warner Valerie Mizrahi Vinayak Singh Sophia Gessner Ryan Dinkele Anastasia Koch Kedebone Oliver Immunology Thomas Scriba Melissa Murphy Electron Microscopy Jeremy Woodward Computational Biology Nicola Mulder Chacha Issarow Electronic Engineering Samuel Ginsberg Computational Fluid Dynamics Arnaud Malan Stewart Swan