The transmission dynamics of tuberculosis in a recently developed Chinese city.
ABSTRACT Hong Kong is an affluent subtropical city with a well-developed healthcare infrastructure but an intermediate TB burden. Declines in notification rates through the 1960s and 1970s have slowed since the 1980s to the current level of around 82 cases per 100 000 population. We studied the transmission dynamics of TB in Hong Kong to explore the factors underlying recent trends in incidence.
We fitted an age-structured compartmental model to TB notifications in Hong Kong between 1968 and 2008. We used the model to quantify the proportion of annual cases due to recent transmission versus endogenous reactivation of latent infection, and to project trends in incidence rates to 2018. The proportion of annual TB notifications attributed to endogenous reactivation increased from 46% to 70% between 1968 and 2008. Age-standardized notification rates were projected to decline to approximately 56 per 100 000 in 2018.
Continued intermediate incidence of TB in Hong Kong is driven primarily by endogenous reactivation of latent infections. Public health interventions which focus on reducing transmission may not lead to substantial reductions in disease burden associated with endogenous reactivation of latent infections in the short- to medium-term. While reductions in transmission with socio-economic development and public health interventions will lead to declines in TB incidence in these regions, a high prevalence of latent infections may hinder substantial declines in burden in the longer term. These findings may therefore have important implications for the burden of TB in developing regions with higher levels of transmission currently.
- SourceAvailable from: Martien W Borgdorff[show abstract] [hide abstract]
ABSTRACT: This study assessed progress towards tuberculosis (TB) elimination in the Netherlands by using DNA fingerprinting. Mycobacterium tuberculosis strains were defined as new if the IS6110 restriction fragment length polymorphism pattern had not been observed in any other patient during the previous 2 years. Other cases were defined as clustered and attributed to recent transmission. In the period 1995-2002, the incidence of TB with new strains was stable among non-Dutch residents and declined among the Dutch. However, the decline among the Dutch was restricted to those >or=65 years of age. Moreover, the average number of secondary cases per new strain did not change significantly over time. We conclude that the decline of TB in the Netherlands over the past decade was mainly the result of a cohort effect: older birth cohorts with high infection prevalence were replaced by those with lower infection prevalence. Under current epidemiologic conditions and control efforts, TB may not be eliminated.Emerging infectious diseases 04/2005; 11(4):597-602. · 5.99 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Foreign-born persons accounted for 57% of all tuberculosis (TB) cases in the United States in 2006. Current TB control strategies have not sufficiently addressed the high levels of TB disease and latent TB infection in this population. To determine the risk of TB disease and drug-resistant TB among foreign-born populations and the potential impact of adding TB culture to overseas screening procedures for foreign-born persons entering the United States. Descriptive epidemiologic analysis of foreign-born persons in the United States diagnosed with TB from 2001 through 2006. TB case rates, stratified by time since US entry, country of origin, and age at US entry; anti-TB drug-resistance patterns; and characteristics of TB cases diagnosed within 3 months of US entry. A total of 46,970 cases of TB disease were reported among foreign-born persons in the United States from 2001 through 2006, of which 12,928 (28%) were among recent entrants (within 2 years of US entry). Among the foreign-born population overall, TB case rates declined with increasing time since US entry, but remained higher than among US-born persons--even more than 20 years after arrival. In total, 53% of TB cases among foreign-born persons occurred among the 22% of the foreign-born population born in sub-Saharan Africa and Southeast Asia. Isoniazid resistance was as high as 20% among recent entrants from Vietnam and 18% for recent entrants from Peru. On average, 250 individuals per year were diagnosed with smear-negative, culture-positive TB disease within 3 months of US entry; 46% of these were from the Philippines or Vietnam. The relative yield of finding and treating latent TB infection is particularly high among individuals from most countries of sub-Saharan Africa and Southeast Asia.JAMA The Journal of the American Medical Association 07/2008; 300(4):405-12. · 29.98 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The Singapore Tuberculosis Elimination Programme (STEP) was launched in 1997 because the incidence of the disease had remained between 49 and 56 per 100,000 resident population for the preceding 10 years. STEP involves the following key interventions: directly observed therapy (DOT) in public primary health care clinics; monitoring of treatment progress and outcome for all cases by means of a National Treatment Surveillance Registry; and preventive therapy for recently infected close contacts of infectious tuberculosis cases. Among other activities are the revamping of the National Tuberculosis Notification Registry, the discontinuation of BCG revaccination for schoolchildren, the tightening up of defaulter tracing, and the education of the medical community and the public. Future plans include an outreach programme for specific groups of patients who are unable to attend their nearest public primary care clinics for DOT, the detention of infectious recalcitrant defaulters for treatment under the Infectious Diseases Act, the molecular fingerprinting of tuberculosis isolates, and targeted screening of high-risk groups. The incidence of tuberculosis fell from 57 per 100,000 population in 1998 to 48 per 100,000 in 1999 and continued to decline to 44 per 100,000 in 2001. With political will and commitment and the support of the medical community and the public it is hoped that STEP will achieve further progress towards the elimination of tuberculosis in Singapore.Bulletin of the World Health Organisation 02/2003; 81(3):217-21. · 5.25 Impact Factor
The Transmission Dynamics of Tuberculosis in a Recently
Developed Chinese City
Peng Wu1, Eric H. Y. Lau1, Benjamin J. Cowling1*, Chi-Chiu Leung2, Cheuk-Ming Tam2, Gabriel M. Leung1
1Department of Community Medicine and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China, 2Tuberculosis
and Chest Service, Department of Health, Government of the Hong Kong SAR, Hong Kong SAR, China
Background: Hong Kong is an affluent subtropical city with a well-developed healthcare infrastructure but an intermediate
TB burden. Declines in notification rates through the 1960s and 1970s have slowed since the 1980s to the current level of
around 82 cases per 100 000 population. We studied the transmission dynamics of TB in Hong Kong to explore the factors
underlying recent trends in incidence.
Methodology/Principal Findings: We fitted an age-structured compartmental model to TB notifications in Hong Kong
between 1968 and 2008. We used the model to quantify the proportion of annual cases due to recent transmission versus
endogenous reactivation of latent infection, and to project trends in incidence rates to 2018. The proportion of annual TB
notifications attributed to endogenous reactivation increased from 46% to 70% between 1968 and 2008. Age-standardized
notification rates were projected to decline to approximately 56 per 100 000 in 2018.
Conclusions/Significance: Continued intermediate incidence of TB in Hong Kong is driven primarily by endogenous
reactivation of latent infections. Public health interventions which focus on reducing transmission may not lead to
substantial reductions in disease burden associated with endogenous reactivation of latent infections in the short- to
medium-term. While reductions in transmission with socio-economic development and public health interventions will lead
to declines in TB incidence in these regions, a high prevalence of latent infections may hinder substantial declines in burden
in the longer term. These findings may therefore have important implications for the burden of TB in developing regions
with higher levels of transmission currently.
Citation: Wu P, Lau EHY, Cowling BJ, Leung C-C, Tam C-M, et al. (2010) The Transmission Dynamics of Tuberculosis in a Recently Developed Chinese City. PLoS
ONE 5(5): e10468. doi:10.1371/journal.pone.0010468
Editor: Ludovic Tailleux, Institut Pasteur, France
Received December 9, 2009; Accepted April 10, 2010; Published May 3, 2010
Copyright: ? 2010 Wu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the Research Fund for the Control of Infectious Disease, Food and Health Bureau, Government of the Hong Kong SAR (ref:
09080802) and the US National Institute of General Medical Sciences (grant no. 1 U54 GM088558, MIDAS Harvard Center for Communicable Disease Dynamics).
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: email@example.com
While tuberculosis (TB) remains a leading cause of death in
many developing countries , some developed countries with low
incidence and prevalence have begun to investigate measures to
eliminate TB [2–4]. Hong Kong is an affluent subtropical city with
a well-developed healthcare infrastructure but a relatively high TB
burden with around 82 cases per 100 000 population in 2008 .
Medical developments, demographic changes and socio-economic
improvements led to dramatic declines in local age-standardized
TB notifications and mortality rates by 56% and 84% between
1960 and 1980, however the decline in notifications has slowed
since the late 1980s [5,6]. We constructed a mathematical model
to study the transmission dynamics of TB in Hong Kong between
1968 and 2008 and to explore the potential factors underlying the
attenuating declines in incidence. Transmission in our model
varies dynamically in proportion to the number of infectious cases,
and we estimate key uncertain parameters including the
transmission coefficients. By specifically accounting in our model
for the routes by which active TB disease developed, we
differentiate notifications due to recent exogenous transmission
versus endogenous reactivation, with implications for control
measures and trends in disease burden in the short- to medium-
Materials and Methods
Sources of Data
Tuberculosis has been a notifiable infectious disease in Hong
Kong since 1939. Annual age- and sex-specific TB notifications
from 1968 to 2008 were obtained from the Department of Health
of the Hong Kong government. The TB notification system was
re-organized in 1967 , leading to a temporary artefactual
fluctuation in notification rates in the late 1960s. Annual age- and
sex-specific mid-year populations, annual birth rates, and age-,
time- and sex-specific death rates from 1961 to 2007 were
obtained from official statistics published by the Census and
Statistics Department (CSD) of the Hong Kong government. We
also adopted the population projections from 2008 to 2018
compiled by CSD [7–10]. Data on local recovery rates of newly
diagnosed TB cases were reported by the TB and Chest Service of
the Hong Kong government . For consistency with local
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statistics, age-specific incidence rates were standardized to the
World Standard Population .
We specified a compartmental model for TB  and
developed the model to explicitly incorporate age structure. The
model is composed of eight compartments or states (Figure 1).
Individuals are born without infection and are assumed susceptible
(S) to infection. An individual who is infected with TB may
develop active TB disease (infectious or non-infectious) immedi-
ately or may have latent TB infection without presenting any
clinical symptoms or signs of active disease. In the latter case, an
individual is described by the model as having recent latent TB
infection (RLTBI). RLTBI is a transient state and after 5 years of
infection the individual in RLTBI transits to the long-term latent
TB infection (LLTBI) state. This structure allows individuals in the
RLTBI state to have a different rate of progression to active TB
disease from those in the LLTBI state.
The route by which active TB disease develops can be classified
into one of the two categories, namely recent exogenous infected/
reinfected and endogenous reactivated TB disease. Active TB
disease which develops within 5 years of first infection or an
infection that was not the first ever infection (i.e. a reinfection) is
classified as recent infected/reinfected infectious TB (RIITB) or
noninfectious TB (RINTB) disease. Active TB disease which
develops from an infection which occurred at least five years
earlier is classed as reactivated infectious TB (RAITB) or
noninfectious TB (RANTB) disease . The progression rate to
active TB disease varies for individuals being infected for no more
than 5 years or more than 5 years [15,16]. The separate pathways
through RLTBI and LLTBI to, RIITB, RAITB, RINTB or
RANTB allow us to quantify the number of active TB cases due to
endogenous reactivation and exogenous recent transmission. The
force of infection is assumed to be frequency-dependent in the
model (Text S1), which is a typical assumption in studying disease
transmission dynamics with heterogeneous contacts [17,18].
Individuals who have had active TB disease, have completed a
full course of treatment and have remained free from relapse for at
least 24 months are classified as recovered (R). Individuals in the
recovered state do not have protective immunity and may later
develop active TB disease either via endogenous reactivation or by
exogenous reinfection with TB. Individuals in every state may die,
represented in the model as an absorbing state - death, with a risk
that varies with age and time.
1. TB transmission varies within and between individuals of
different age groups to reflect the age structure in the mixing
pattern. In our model we classify individuals into three age
groups: children (aged from 0 to 15 years), younger adults (aged
from 16 to 30 years), and older adults (aged 31 years or older).
We used this classification since individuals aged 16–30 years
old may be the most active group with more social contacts
with each other than any other age groups.
2. The disease progression rates differs for infected individuals in
different age groups (Text S1 and Figure S1)
3. Individuals who recover from active TB disease do not have
protective immunity against subsequent reinfection .
Figure 1. The schematic framework of the TB transmission dynamic model. The absorbing death state is not shown.
TB Dynamics in Hong Kong
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4. Individuals with active TB disease (infectious or non-infectious)
cannot be re-infected before recovering from the current
5. Individuals in the RLTBI state (having been infected not more
than 5 years without an active disease episode) cannot be re-
infected before recovering from the current infection, while
individuals in the LLTBI state (having been infected more than
5 years without an active disease episode) have the same risk of
reinfection as susceptible individuals.
Model Parameterization, Estimation and Validation
We constructed a demographically appropriate model of the
Hong Kong population from 1961 through 2008 by incorporating
local data on annual birth rates and death rates, as well as on age-
and time-specific changes in the population via immigration and
emigration (Text S1). Table 1 defines the fixed parameters of our
transmission model, listing the values and ranges that are based on
local data where available and otherwise based on data from the
literature. Further details of the variables and notations used in the
model are provided in Text S1 and Table S1.
In addition to the fixed parameters, we estimated six key
parameters for which the values could not be derived from historical
data or the literature and were likely to be specific to the local
situation (Table 2), namely the infection parameter (b), the
proportion of new infections directly developing into infectious or
non-infectious TB disease (a), disease progression rate within the first
5 years after infection (pr) and after being infected for more than 5
years (pl) for the reference group (aged 24), and two relative
transmission factors in the transmission matrix represented by M1
and M2, indicating the relative transmission risk within children and
within younger adults, respectively, compared to the transmission
within older adults (Text S1). We initialized the model in 1961,
assumed the prevalence of TB infection in different age groups
following a logistic distribution (Text S1 and Figure S2), and used a
likelihood function based on a negative binomial distribution to fit
the model to age-specific annual TB notification rates from 1968
burn-in period to minimize the influence of the initial state. We used
maximum likelihood to estimate the six parameters inthe model and
evaluated the information matrix numerically to estimate marginal
95% confidence intervals. The model was validated by comparing
TB incidence predicted by the fitted model with observed age-
specific TB notifications from 2004 through 2008 and by the
consistent correlation with the TB transmission dynamics showed in
the correlation matrix of the estimated parameters (Table S2). We
used the model to project future age-specific TB notifications from
2009 through 2018, with 95% prediction intervals.
We performed one-way sensitivity analyses to examine the
influence of each of the fixed parameters on the trends in TB
notifications predicted by the model. We varied the proportion of
active TB disease which is infectious (h), the proportion of active
TB disease from latent TB infection (RLTBI or LLTBI) which is
infectious (c), the probability of relapse for recovered patients (v),
Table 1. Summary of fixed parameter values used in the model.
ParameterUnits Parameter value
Range of sensitivity
Period-specific birth rate (d(t))/year 
All-cause death rate (m(a,t)) /person/year
Recovery rate for infectious or non-infectious TB patients in 1961 (w (0))/person/year0.20.1–0.5
Proportion of developing infectious TB directly from the susceptible,
LLTBI or recovered state (h)
Proportion of developing infectious TB from latent TB infection (c)0.85 0.50–1.00
Probability of relapse for recovered patients (v) /person/year0.017 0.016–0.018
The prevalence of latent TB in 1961 (PL0) 0.70.1–0.9
Ratio of TB prevalence to incidence cases in 1961 (pT0) 2.50.1–5.0
Relative risk of disease progression in different age groups (k(a))See Appendix Figure 2 [15,16]
Table 2. Summary of parameters estimated in the model.
ParameterUnit Estimated value95% confidence interval (CI)
Infection parameter (b)/person/year14.7(14.1, 15.7)
Relative transmission factor (M2) 7.1 (6.4, 7.9)
Relative transmission factor (M1)0.19(0.17, 0.21)
Proportion of new infections directly developing infectious or non-infectious TB from
susceptible, LLTBI or recovered state (a)
0.013 (0.011, 0.015)
Disease progress rate within the first 5 years after infection for the reference group (aged 24) (pr) /person/year0.0018(0.0015, 0.0022)
Disease progress rate after being infected for more than 5 years for the reference group
(aged 24) (pl)
TB Dynamics in Hong Kong
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TB Dynamics in Hong Kong
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the recovery rate for TB patients in 1961 (w(0)), the prevalence of
latent TB in 1961 (PL0), and the ratio of TB prevalence to
incidence cases in 1961 (pT0). Each parameter was varied between
minimum and maximum plausible values as determined from local
data or the literature (Table 1).
We performed a multivariate sensitivity analysis based on Latin
hypercube sampling to examine the influence of all the fixed
each parameter (Table 1) into 100 equiprobable intervals. We then
simulated 100 sets of samples in which each variable was drawn
randomlyand withoutreplacementfromtheseintervals. Eachofthe
100 sets of fixed parameters was used in place of the original values
in the model to explore uncertainties in the total number of
notifications, and the proportion due to recent transmission or
endogenous reactivation. We also tested the plausibility of
alternative relative transmission risk matrix across age groups.
Table 2 lists the parameter estimates and 95% confidence
intervals for the six estimated parameters in the model fitted to
notifications from 1968 through 2003. The annual number of
newly developed active TB cases predicted by the best-fitting
model closely matched the trends in total TB notifications as well
as the age-standardized notification rates in Hong Kong from
1968 through 2008 (Figure 2). After the 1970s the number of cases
due to recent transmission declined much more rapidly than the
number of cases due to endogenous reactivation. Between 1968
and 2008 the proportion of annual TB notifications attributed to
endogenous reactivation increased from 46% to 70% (Figure 2a).
Under the fitted model, notification rates are projected to continue
to decline slowly after 2008, with age-standardized incidence rates
approaching 56 per 100 000 in 2018.
The model was able to closely match age-specific TB incidence
to trends in local notifications from 1968 through 2008 (Figure 3).
Throughout the period, most notifications in the older age groups
were estimated to be a result of endogenous reactivation, while
most cases among teenagers and younger adults were estimated to
be attributable to recent transmission. Allowing for age depen-
dency in the risk of disease progression, the estimated lifetime risk
of TB disease for infected individuals was around 1%–2%.
In one-way sensitivity analyses, none of the parameters had a
substantial influence on the predicted number of TB notifications
when varied within plausible ranges (data not shown). In the
multivariate sensitivity analysis we found that the main inferences
remain unchanged, while the proportion of cases due to recent
transmission in 1968 and 2008 ranged from 29% to 65% and 22%
to 34%, respectively (Figure 4). Models based on alternative
relative transmission risk matrices could not fit the notified TB
cases better, as shown by much higher values of AIC, however, the
proportion of cases due to recent transmission did not change
substantially compared with the previous model, decreasing from
around 40% to 20% in 1968–2008.
The relative importance of recent exogenous infection/
reinfection and endogenous reactivation on TB epidemics has
been a controversial issue [21–23]. While at diagnosis it may be
difficult to determine whether an individual case has resulted from
recent exogenous infection/reinfection or endogenous reactivation
of a long-term latent infection, the distinction is important for TB
control. In this study we examined TB transmission dynamics in
Hong Kong using a mathematical model  extended to
incorporate age-structure which allowed us to attribute new cases
to either recent transmission or endogenous reactivation. We
found that the dominant force responsible for the attenuating
declines in local TB incidence is a substantial proportion of
notifications arising from endogenous reactivation of latent
infections, even with a low estimated progression rate to active
TB disease [24,25]. A previous study of TB transmission dynamics
in Hong Kong used a model fitted to notifications from 1967
through 1978 where the risk of infection was independent of the
number of infectious cases and independent of age . In that
study, a scenario with a relatively high risk of disease and relatively
low transmission was most similar to observed trends in
notifications, suggesting that local trends are being driven by
endogenous reactivation, and estimated a high risk of disease. In
our model we allowed transmission to vary dynamically with the
number of infectious cases, and we estimated the progression rate
to active TB disease to be relatively low, with a lifetime risk of 1%–
2% which is lower than the reported 5%–10% for individuals
infected in the pre-chemotherapy era  perhaps due to general
health improvements at the societal level since the 1970s or
suggestive of different risks of disease progression in different
Under our model, the proportion of TB cases attributable to
recent transmission has substantially decreased since the 1970s.
This decline may be attributed to the improvement of TB control
measures in Hong Kong since the 1960s, in particular the
implementation of directly observed treatment short-course
(DOTS) in the late 1970s . The reduction of infectious TB
cases via effective treatment appears to have had a substantial
impact on transmission . Endogenous reactivation, however,
develops from possibly long-term latent infection, and may be
greatly influenced by longer-term demographic and socio-
economic changes . Hong Kong has been largely an immigrant
community. The majority of older local residents were born and
grew up in southern China, where risks of TB may have been
quite different . Endogenous reactivation of latent disease is
also likely to be affected by rates of comorbidities including
diabetes . behavioural factors such as smoking , as well as
immunosenescence . Hong Kong has a long life expectancy
and an aging population, many of whom may have latent
infection, and therefore the burden of TB from endogenous
reactivation may not be substantially reduced by the current focus
on effective treatment of active TB cases with DOTS as a primary
The transmission of TB primarily depends on the infectiousness
of active TB cases, the susceptibility of individuals, and contact
patterns between susceptible individuals and infectious TB
patients. Given the potential for different contact patterns within
and between different groups, we divided the Hong Kong
population into children, younger adults and older adults in our
model. The estimated parameters from the model suggest that the
Figure 2. TB incidence in Hong Kong. (a) Observed TB notifications from 1968 through 2008 (black) compared to fitted total (blue), recently
transmitted (green) and reactivated (red) TB cases from 1968 through 2003, and predicted total (blue dashed), recently transmitted (green dashed)
and reactivated (red dashed) TB cases from 2004 through 2018, with 95% prediction interval (blue dotted). (b) Observed age-standardized TB
notification rates from 1968 through 2008 compared to fitted (blue) and age-standardized TB notification rates from 1968 through 2003, and
predicted (blue dashed) TB notification rates from 2004 through 2018.
TB Dynamics in Hong Kong
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TB Dynamics in Hong Kong
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transmission of TB is highest within younger adults and is lowest
within children in Hong Kong. The estimated force of
transmission in our model reflects not only contact patterns but
also the transmissibility of TB within different age groups (Text
S1). Although effective contacts within children in Hong Kong
may not be less frequent than other age groups, and may even be
more frequent, we estimated that the force of transmission of TB
within children is still lower than other age groups. One possible
explanation of this is that incident disease in children may be more
likely to be primary disease which is less infectious than post-
primary TB often observed in adults . In the period studied in
our model, more than 99% of children in Hong Kong received
BCG vaccination at birth [5,33], which prevents the haematog-
enous dissemination of tubercle bacilli in infected children .
Therefore another possible explanation is that BCG vaccine has
led to reductions in transmission in children.
There are some limitations in our analyses. First, we assumed
that the progression rates to develop active TB were constant
throughout the whole study period, which might underestimate
the progression rates in the earlier years and overestimate it more
recently, due to socio-economic improvements or other factors.
There are few data in the literature on progression rates, and
without such information it is difficult to include additional
parameters in our model, although we have specifically allowed for
the risk of progression to be higher in the first five years after
infection. Nevertheless assuming constant rates in our model was
sufficient to describe TB dynamics in Hong Kong in the past four
decades; in further work we may examine the support for more
complicated assumptions such as period-specific progression rates.
Second, we did not include partial immunity into the model,
which might have led us to underestimate the role of endogenous
reactivation on the transmission of TB in Hong Kong. If
reinfection is less common due to partial immunity, a greater
proportion of cases in older individuals would be associated with
endogenous reactivation and the estimates from our model on the
role of reactivation may be slightly conservative. However with
low incidence rates, reinfection was relatively rare and if we had
included partial immunity it is unlikely that the conclusions of our
study regarding the relative importance of endogenous reactiva-
tion would have changed substantially. Third, although in Hong
Kong around 65% of cases are in males , we neglected
potentially different transmission dynamics between males and
females because in our model we aimed to understand the most
important elements affecting the population dynamics of TB.
There are few data to explain the differences between males and
females, particularly in the potentially different contact patterns
Figure 3. Observed TB age-specific notifications compared to fitted and predicted total (blue), recently transmitted (green) and
reactivated (red) TB cases at 5 year intervals from 1968 through 2008, and model predictions for 2011 and 2016.
Figure 4. Multivariate sensitivity analysis. (a) observed TB notifications, (b) estimated reactivated TB notifications, and (c) estimated recently
parameters under Latin hypercube resampling; (d) proportion of new notifications due to recent transmission at 5 year intervals from 1968 through 2018.
TB Dynamics in Hong Kong
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historically, while there is some evidence that differential smoking
rates or access to healthcare may be partially responsible
[30,35,36]. Fourth, we allowed for age-specific mixing in our
model, however if TB dynamics in Hong Kong are more complex
we may have underestimated the role of re-infection in some
groups . The pattern of age-specific TB incidence in adults
was bimodal in the 1970s and 1980s but incidence became more
similar across ages after the mid-1990s. We tried to use a
parsimonious model to explain the general trends in age-specific
TB incidence, but we may not have fully incorporated all sources
of time varying factors to capture more subtle changes in
incidence. Hence the predicted fluctuations in the age-specific
incidence rate under our model should not be interpreted as excess
incidence at certain ages. Lastly, we fitted our model by comparing
predicted cases to observed notifications, essentially assuming a
100% detection rate, which might underestimate the actual
burden of TB in Hong Kong. Nevertheless, this is not likely to
lead to substantial bias since Hong Kong has had a well-
established TB control system for decades, and in a detailed audit
the detection rate was estimated to be around 95% .
In conclusion, endogenous reactivation of long-term latent
infection is an important component in the intermediate burden of
TB in Hong Kong, currently accounting for more than 80% of
new notifications. In line with the Millennium Development Goals
proposed by the United Nations, the Stop TB Partnership
launched the Global Plan to Stop TB in 2006 aiming to decrease
TB morbidity and mortality by 50% by 2015 compared with the
levels in 1990, and to eliminate TB worldwide by 2050 [39,40].
The primary proposed means to achieve the 2015 target is an
expansion of DOTS and construction and improvement of
healthcare infrastructure. While a well-implemented effective
treatment programme and active disease detection system may
be effective in settings with high transmission, in the long-term and
in developed settings it may also be important to focus on early
detection of potentially reactivated disease, and screening to
identify individuals with latent TB infection followed by treatment
to prevent endogenous reactivation to active disease. Hong Kong
has experienced rapid development since 1945, and our findings
have important implications for the burden of TB in developing
regions with higher levels of transmission currently. While
reductions in transmission with socio-economic development and
public health interventions will lead to declines in TB incidence in
these regions, a high prevalence of latent infections may hinder
substantial declines in burden in the longer term.
Found at: doi:10.1371/journal.pone.0010468.s001 (0.09 MB
Summary of the variables and notation used in the
on data from 2003–2018.
Found at: doi:10.1371/journal.pone.0010468.s002 (0.03 MB
Correlation matrix of the estimated parameters based
infected individuals in different age groups.
Found at: doi:10.1371/journal.pone.0010468.s003 (0.23 MB TIF)
The relative risk of disease progression for TB-
infection in the initial state in 1961. L1, L2, L3, L4 and L5
represent the prevalence of individuals who have been infected
with TB for over 1, 2, 3, 4, 5 years but had not developed active
TB disease in Hong Kong prior to 1961.
Found at: doi:10.1371/journal.pone.0010468.s004 (0.31 MB
The age-specific prevalence of latent tuberculosis
Found at: doi:10.1371/journal.pone.0010468.s005 (0.10 MB
Technical details of the model.
We acknowledge technical support from Vicky Fang and Lincoln Lau.
Conceived and designed the experiments: BJC GML. Performed the
experiments: PW EHYL. Analyzed the data: PW EHYL BJC CCL CMT.
Wrote the paper: PW EHYL BJC CCL CMT GML.
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