Pi Is 2666606523000883

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Tuberculosis in older adults: challenges and best practices in

the Western Pacific Region
Alvin Kuo Jing Teo,a,b,c,o,∗ Fukushi Morishita,d,o Tauhid Islam,d Kerri Viney,e,p Catherine W. M. Ong,f ,g,h Seiya Kato,i HeeJin Kim,j Yuhong Liu,k
Kyung Hyun Oh,d Takashi Yoshiyama,i Akihiro Ohkado,i Kalpeshsinh Rahevar,d Lisa Kawatsu,i Manami Yanagawa,d Kiesha Prem,a,l Siyan Yi,a,m,n
Huong Thi Giang Tran,d,p and Ben J. Maraisb,c,p
a
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore,
Singapore
b
Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
c
The University of Sydney Institute for Infectious Diseases (Sydney ID) and the Centre of Research Excellence in Tuberculosis (TB-CRE),
Sydney, NSW, Australia
d
World Health Organization, Regional Office for the Western Pacific, Manila, Philippines
e
World Health Organization, Global Tuberculosis Programme, Geneva, Switzerland
f
Infectious Diseases Translational Research Programme, Department of Medicine, National University of Singapore, Singapore,
Singapore
g
Division of Infectious Diseases, Department of Medicine, National University Hospital, Singapore, Singapore
h
Institute of Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore
i
Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan
j
Korean National Tuberculosis Association, Seoul, Republic of Korea
k
Beijing Chest Hospital, Capital Medical University, Beijing, China
l
Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
m
KHANA Center for Population Health Research, Phnom Penh, Cambodia
n
Center for Global Health Research, Public Health Program, Touro University California, Vallejo, CA, USA
Summary The Lancet Regional

Health - Western Pacific
The Western Pacific has one of the fastest-growing older adult populations globally, and tuberculosis (TB) remains
2023;36: 100770
one of the foremost infectious causes of disease and death in the region. Older adults are at higher risk of TB due to
Published Online 20 April
immunosenescence, comorbidities, and increased institutionalisation. Atypical symptoms and reduced access to 2023
health services may delay care-seeking and TB diagnosis, while co-morbidity and increased risk of adverse drug https://doi.org/10.
reactions complicate TB treatment. Post-TB sequelae and socioeconomic challenges may decrease the quality of life 1016/j.lanwpc.2023.
after TB treatment completion. Despite their high disease burden and special challenges, there is a lack of regionally 100770
coordinated policies and guidelines to manage TB among older adults. Routine TB screening at aged-care facilities,
age-friendly infrastructure and services, awareness of atypical TB features, integration of TB and non-communicable
diseases services, and person-centred approaches to treatment support could improve TB management among older
adults. Addressing these challenges and adopting the best practices identified should inform policy formulation and
implementation.
Funding This project was funded by 1) the World Health Organization Regional Office for the Western Pacific, with
financial contributions from the Government of the Republic of Korea through the Korean Disease Control and
Prevention Agency and the Government of Japan through the Ministry of Health, Labour and Welfare, and 2) NUS
Start-up Grant. The funders had no role in the paper design, collection, analysis, and interpretation of data and in
writing of the paper.
Copyright © 2023 World Health Organization. Published by Elsevier Ltd. This is an open access article under the CC
BY IGO license (http://creativecommons.org/licenses/by/3.0/igo/).
Keywords: Tuberculosis; Aged; Policy
*Corresponding author.
E-mail addresses: [email protected] (A.K.J. Teo), [email protected] (F. Morishita), [email protected] (T. Islam), [email protected] (K. Viney),
[email protected] (C.W.M. Ong), [email protected] (S. Kato), [email protected] (H. Kim), [email protected] (Y. Liu), ohk@
who.int (K.H. Oh), [email protected] (T. Yoshiyama), [email protected] (A. Ohkado), [email protected] (K. Rahevar), kawatsu@jata.
or.jp (L. Kawatsu), [email protected] (M. Yanagawa), [email protected] (K. Prem), [email protected] (S. Yi), [email protected]
(H.T.G. Tran), [email protected] (B.J. Marais).
o
These authors contributed equally to this work.
p
These authors are joint senior authors.
www.thelancet.com Vol 36 July, 2023 1

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Background where enhanced TB management has reduced TB

The Western Pacific Region, home to 1.9 billion people in transmission within communities, leading to a relative
37 countries and areas, has one of the largest and fastest- increase in reactivation disease among older people in the
growing populations of older adults globally. The average coming decades.17 Given various TB disease burdens in
life expectancy of people in the region was 77.7 years in the Western Pacific Region,18 both reactivation pathway
2019, 4 years above the global estimate (73.3 years).1,2 The and exogenous infection/re-infection pathway should be
increased TB risk of this ageing population poses a major considered, especially in households and congregate
public health challenge. While TB deaths have gradually settings such as aged care facilities and hospitals.13,16,19,20
declined across all age groups since the 1990s, TB remains Institutional transmission among residents and staff
one of the leading infectious causes of death worldwide, within and between aged-care and health facilities has
with increasing age recognised as a major risk factor for been reported,13,20,21 posing a major infection control
TB-related death.3,4 In 2021, the estimated incidence in the challenge, particularly if disease detection is delayed.
Western Pacific Region was the highest among persons Increasing immunosenescence in older individuals, a
aged ≥65 years (men—255,000 and women—116,000), process of age-associated immune dysfunction, increases
accounting for 19.5% of the total TB incidence.5 Between the risk of TB reactivation.19,22,23 In addition, the presence of
2020 and 2021, people with TB aged ≥65 years made up a other comorbidities that increase with age, such as dia-
large proportion of the notified TB cases in countries and betes, could experience ≥1.5-folds increased risk of
areas such as Japan (69%), the Republic of Korea (51%), developing TB.24–26 The prevalence and severity of chronic
and Hong Kong Special Administrative Region, China respiratory disease, including chronic obstructive pulmo-
(hereinafter Hong Kong SAR) (45%).5 nary disease (COPD) and bronchiectasis, increase as a
Failure to control and manage TB among older person ages.27 The relationship between chronic respira-
adults places them at risk and could also perpetuate tory disease and TB, both as a cause and a consequence, is
transmission to other age groups. Given the absence of more significant in high TB incidence settings.28 Another
regional guidance on how best to deal with this chal- condition prevalent among older adults is undernutri-
lenge, a careful assessment of the situation is required tion,29 especially among those living in aged care facil-
to assist countries in meeting ambitious End TB Strat- ities.30 Undernutrition leads to impaired immune
egy targets.6 In this article, we describe the risk factors function, thereby increasing the risk of TB reactivation and
for TB disease and transmission and the clinical disease the risk that a new infection will rapidly progress to TB
manifestations of TB in older adults, with a focus on the disease.31,32 The detrimental synergistic effect of ageing,
Western Pacific Region. We also highlight key chal- diabetes, and undernutrition on the immune system ele-
lenges, relevant strategies, and associated research pri- vates the vulnerability of older adults to develop TB,
orities related to TB transmission, detection, diagnosis, including from drug-resistant strains.24,33 With improved
treatment, and post-TB health (See on-line health care, people living with HIV are also ageing and
Supplementary Material for a detailed description of therefore are at risk of similar age-related comorbidities.34
the literature search methods and limitations).
Clinical disease manifestations
Contextual heterogeneity Typical pulmonary TB symptoms such as prolonged
The Western Pacific Region includes a diverse range of cough, haemoptysis, night sweats, chills, fatigue, and
countries and areas with different population structures, loss of appetite are less prominent in older adults with
cultural beliefs and social norms, economic resources, TB,35,36 while those with extrapulmonary TB usually
and healthcare systems. This heterogeneity reflects dif- experience symptoms localised to the site of disease.
ferences in TB transmission risk, as well as risk factors Disseminated TB, which more frequently occurs in
for disease development, which contributes to variable immunocompromised individuals or people with
disease burden observed among older adults in different immunosenescence, is associated with non-specific
countries and states (Table 1). symptoms such as unexplained fever and weight loss.35
In settings with a lower TB burden and limited The presentation of TB-associated symptoms may also
community transmissions, such as Hong Kong SAR, be confounded by concurrent comorbidities, making TB
Japan, and Singapore, TB incidence among older adults more challenging to diagnose in older adults. Radio-
is mainly driven by increased rates of reactivation logical features also differ between younger and older
disease.12–14 In high-burden settings such as Cambodia adults,37 with older adults less likely to have lung nod-
and Viet Nam with evidence of ongoing community ules or consolidation on computed tomography (CT)38 or
transmission, older adults are at risk of developing TB typical apical lung cavities on the chest radiograph.39–41
disease through both reactivations of past TB infection The presence of lung nodules and soft tissue masses
and disease progression following recent primary or re- is also more likely to indicate malignancies in older
infection.15,16 China demonstrates a country in transition adults, which may co-exist with TB disease.
2 www.thelancet.com Vol 36 July, 2023

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Countries and areas Country UHC indices of TB incidence rate Epidemiological Estimated Estimated TB % of incident BCG
income service per 100,000 classification9 for TB TB case incidence in TB cases in coverage10,c
7,f
classification coverage population per based on incidence load5,e,f older adults5,e,f older adults5,f
20198,d year5,e,f rate5,e,f
Western Pacific Region 8011 98 1,900,000 371,000 19.5% 89.0%
a
Philippines Lower-middle 55 650 Severely endemic 741,000 78,000 10.5% 47.0%
Marshall Islands Upper-middle N/A 483 Highly endemic 200 10 5.0% 83.0%
Mongoliaa Lower-middle 63 428 Highly endemic 14,000 1080 7.7% 99.4%
Papua New Guineaa Lower-middle 33 424 Highly endemic 42,000 920 2.2% 42.0%
Kiribati Lower-middle 51 424 Highly endemic 550 35 6.4% 96.0%
Tuvalu Upper-middle N/A 296 Endemic 33 6 18.2% 100.0%
Cambodiab Upper-middle 61 288 Endemic 48,000 8900 18.5% 92.0%
Nauru High N/A 193 Endemic 24 2 8.3% 100.0%
Viet Nama Lower-middle 70 173 Endemic 169,000 41,000 24.3% 87.9%
Lao People’s Democratic Republic Lower-middle 50 143 Endemic 11,000 2010 18.3% 81.4%
Malaysia Upper-middle 76 97 Upper moderate 33,000 5400 16.4% 99.0%
Northern Mariana Islands High N/A 81 Upper moderate 40 7 17.5% 13.0% (2010)
Micronesia (Federated States of) Lower-middle 48 80 Upper moderate 90 0 0.0% 59.2%
Fiji Upper-middle 61 66 Upper moderate 610 49 8.0% 99.6% (2020)
Solomon Islands Lower-middle 50 65 Upper moderate 460 40 8.7% 83.5%
Brunei Darussalam High 77 61 Upper moderate 270 58 21.5% 99.9%
China, Macao SAR High N/A 57 Upper moderate 390 143 36.7% 99.7%
China, Hong Kong SAR High N/A 57 Upper moderate 4300 1920 44.7% 95.0%
Chinaa Upper-middle 82 55 Upper moderate 780,000 210,000 26.9% 99.7%
Palau Upper-middle N/A 51 Upper moderate 9 0 0.0% N/A
Niue N/A N/A 48 Lower moderate 0 0 0.0% 88.0%
Singapore High 86 48 Lower moderate 2800 720 25.7% 98.0% (2018)
Republic of Korea High 87 44 Lower moderate 23,000 11,700 50.9% 98.0% (2019)
Guam High N/A 39 Lower moderate 67 10 14.9% N/A
Vanuatu Lower-middle 52 34 Lower moderate 110 9 8.2% 76.0%
Tokelau N/A N/A 19 Upper moderate 0 0 0.0% 100.0%
French Polynesia High N/A 13 Lower moderate 39 8 20.5% 96.0% (2019)
Cook Islands N/A N/A 13 Lower moderate 2 0 0.0% 100.0%
Japan High 85 11 Lower moderate 13,000 9200 70.8% 95.0% (2020)
New Caledonia High N/A 10 Lower moderate 29 14 48.3% 95.0% (2018)
Tonga Upper-middle 56 7.6 Low incidence 8 2 25.0% 100.0%
New Zealand High 86 6.8 Low incidence 350 54 15.4% 9.9%
Samoa Lower-middle 53 6.8 Low incidence 15 3 20.0% 92.0%
Australia High 87 6.5 Low incidence 1700 290 17.1% N/A
American Samoa Upper-middle N/A 4.1 Low incidence 2 1 50.0% 91.0% (1998)
Wallis and Futuna Islands N/A N/A 1.9 Low incidence 0 0 0.0% 97.0% (2016)
Pitcairn Islands N/A N/A N/A N/A N/A N/A N/A N/A
BCG; Bacillus Calmette–Guérin, N/A; data not available, SAR; special administration region, TB; tuberculosis, UHC; Universal health coverage. aWHO high TB burden country. bRecently removed from the
WHO high TB burden list and was included on a global TB watchlist. cLatest data (2021) is presented unless otherwise stated. If official, administrative, and WHO/UNICEF estimates are provided for the
same year, official data is presented. dAverage coverage of essential services based on tracer interventions that include reproductive, maternal, newborn and child health, infectious diseases, non-
communicable diseases and service capacity and access, among the general and the most disadvantaged population. The indicator is an index reported on a unitless scale of 0–100, with 0 being the worst,
and 100 the best. eThese estimates (including those used for grouping) have uncertainty ranges but only best estimates are provided in the table and were used for calculating % of incidence TB cases (age
≥65 years). fAll data for 2021 (as stated in heading, unless otherwise specified).
Table 1: Epidemiological profiles and variable TB incidence among older adults in countries and areas in the Western Pacific Region (2021).
Key challenges in addressing TB among older TB infection management

adults Aged-care facilities where TB infection is common in
Fig. 1 and Supplementary Table S1 provide an overview older people represent congregate settings with a high
of key challenges along the TB care cascade with a brief risk of TB transmission. In general, the WHO recom-
description of the best practices identified to overcome mends the traditional tuberculin skin test (TST) and
them. newer interferon-gamma-releasing assays (IGRAs) to

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Fig. 1: Key challenges faced by older adults along the TB care pathway and the corresponding best practices identified to overcome these
barriers. Red boxes represent key challenges, and blue boxes reflect best practices to address them. TB; tuberculosis, TPT; TB preventive
treatment.
test for TB infection. Nonetheless, age-related immu- toxicity in older adults is acknowledged with uncertain
nosenescence may reduce overall sensitivity,42–45 risk-benefit ratios.57 TPT has important short- and long-
although newer generation IGRAs have reported better term benefits in preventing TB disease among those
performance in detecting TB infection among older with TB infection or re-infection.57 TB infection testing
adults.46 The utility of TST for TB infection testing and TPT were also recommended for other household
might also be affected by Bacillus Calmette–Guérin contacts of people with bacteriologically confirmed TB
(BCG) vaccination status (BCG coverage by countries and other at-risk populations, such as those receiving
and areas is provided in Table 1),47 and nutritional sta- tumour necrosis factor inhibitors, dialysis, and organ/
tus.48 The systematic screening of older adults for TB haematological transplants. Consideration should also
infection using TST or IGRA is not currently recom- be given to incarcerated people, health workers, home-
mended by the WHO. less people, and people who use drugs.57 In general,
A recent study among aged-care residents favoured however, systematic treatment of older adults for TB
IGRA over TST in predicting future TB disease.38,49 In infection is not recommended by WHO at present. The
practice, the preferred test will depend on local avail- adverse effects of the TPT regimen, such as the hepatic
ability, accessibility, and cost,50,51 especially in low- adverse effects of isoniazid, the most commonly used
income settings. The adoption of TB infection TPT drug, in older adults, remain a concern.58,59 More-
screening strategies among older adults in the national over, in a survey among national TB programs of high-
policies also relies on the availability of evidence, burden countries (including lower-middle-income
including risk-benefit assessments, which are currently economies in the region: Philippines, Papua New
lacking. Guinea, Cambodia, and Viet Nam), the lack of time and
Apart from the residents, the caretakers and staff at funding for procurement and implementation of the
these facilities are also at risk of TB infection and dis- safer and shorter TPT regimen was reported as barriers
ease, contributing to TB transmission.52–56 In China, TB to their inclusion in the national policies.60
preventive treatment (TPT) among older adults was
projected to be the single most impactful intervention to TB diagnosis and detection
reduce TB incidence and mortality.17 The WHO now Delayed TB care-seeking
conditionally recommends expanded TPT for children Older adults may face significant challenges in access-
≥5 and adults (in addition to children <5 years) in ing TB services, which can be attributed to various socio-
household contact with someone who has bacteriologi- economic and health system challenges. Challenges
cally confirmed pulmonary TB who does not have active include a lack of comprehensive support systems to help
TB disease. However, the greater risk of drug-related manage the complex health issues that

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disproportionately affect this population, as well as of those with initial missed diagnosis were aged >60
physical and financial barriers that impede healthcare years.77 Clinicians’ lack of responsiveness to health
access.61–66 In situations where social security and pro- concerns expressed by older adults has also been
tection schemes are inadequate, older adults with perceived as a barrier to health care delivery.78
limited financial means or independence may be A critical factor in determining the validity of any
reluctant to impose on others to initiate the care-seeking sputum-based test is the quality of the sputum specimen
process.66 This could potentially result in more advanced provided, and older adults may struggle to produce an
disease at the time of diagnosis, making treatment more adequate expectorated sputum sample.15 An assessment
difficult and expensive, and incurring a greater cost of sputum smear results in four countries (including
burden on the person and household affected by TB. For Mongolia) reported higher proportions of low-grade
instance, in China, the median time from symptom positive smears reported in populations at the ex-
onset to TB disease diagnosis was >90 days among older tremes of ages.79 Samples with low bacillary load reduce
adults,67 and this population has 4 times the odds of the sensitivity of microscopic examination, resulting in
experiencing catastrophic costs due to TB compared to missed cases of TB.79,80 Delays in TB diagnosis and
younger adults.68 treatment initiation, as well as inappropriate isolation
A systematic review that assessed healthcare access facilitates nosocomial TB transmission.31 There is a wide
among older females living in rural settings reported spectrum of TB disease risk and presentation across
long waiting times (reported by studies in Nigeria, In- finer age groups,81 with the extent of delay in care-
dia, the United States of America, and China), limited seeking, diagnosis and treatment and the outcomes of
medical resources (reported by studies in Ghana and TB treatment generally worse in the older age groups.41
South Africa), and poor attitude of healthcare staff to- This may have implications for aged-based surveillance
wards older adults (reported by studies in South Africa, and tailored treatment.
India, and China), as barriers to health service uti-
lisation.69 In Cambodia, private healthcare-seeking was TB treatment and adherence
common upon falling ill with TB, as it was perceived to Drug–drug interactions due to the treatment of existing
provide better care and higher quality medicines.70 comorbidities
However, access to TB diagnostics in the Cambodian Polypharmacy, often defined as the simultaneous use of
private sector was reported to be limited. ≥5 medications, is common among older adults. A
Older adults are more likely to dismiss TB symptoms recent systematic review reported a pooled prevalence of
due to concurrent medical conditions, such as existing 37% (36% among studies conducted in Asia).82 A sepa-
cough due to smoking-induced chronic lung disease, rate systematic review conducted among residents of
misconceptions of TB disease risk, and fear of aged-care facilities reported the prevalence of poly-
discrimination, leading to delayed care-seeking and TB pharmacy ranging from 38% to 91%.83 The pooled
diagnosis.62,64,71 Inadequate TB awareness and knowl- prevalence of polypharmacy among older adults in
edge were also documented among older adults who China was estimated to be 48%, with three-quarters
reported lower TB knowledge, attitude, and practice occurring in in-patient settings.84
scores in China.72 However, few studies explored care- For older adults with TB, the co-administration of TB
seeking behaviours and other predictors of delayed TB treatment with drugs used to manage co-morbid con-
diagnosis among older adults in the Western Pacific ditions frequently lead to drug–drug interactions that
Region. In general, TB care-seeking behaviour is influ- may adversely affect clinical outcomes. For instance,
enced by local cultural practices, beliefs, and social rifampicin could reduce the therapeutic levels of some
norms,73 as well as universal challenges related to drugs, such as the antiarrhythmic drug amiodarone, the
healthcare cost, accessibility and perceived levels of care. anticoagulant warfarin and other novel oral anticoagu-
lants, and anti-diabetic drug rosiglitazone.85 Isoniazid
Delayed diagnosis may cause increased hepatotoxicity if used with para-
On presentation to health facilities, TB is often mis- cetamol, alcohol, or valproic acid.85 The use of common
diagnosed due to atypical presentation in older over-the-counter medications, such as antacids, could
adults.55,74,75 TB diagnosis in older adults is further also reduce the concentrations of isoniazid and
complicated by challenges related to advanced age, such rifampicin.85
as cognitive impairment, hearing loss, and communi-
cation difficulties.71 Non-specific TB symptoms and low Higher risk of TB drug toxicities
awareness among health practitioners,76 especially in In general, older adults are at higher risk of adverse
lower TB incidence settings, also contribute to delayed drug events than younger people. Increasing age is a
diagnosis. Between 2012 and 2016, data from the na- risk factor for hepatotoxicity associated with isoniazid
tional health insurance system in the Republic of Korea and rifampicin.31 The risk of pyrazinamide-related
showed that 7186 people diagnosed with TB were not adverse events also increases with age, with liver
recognised on initial hospitalisation; the majority (64%) toxicity and gastrointestinal intolerance being the most

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commonly reported side effects.86,87 For older adults who Post-TB health and rehabilitation
are unlikely to tolerate pyrazinamide, a treatment While TB is curable, TB survivors often experience long-
regimen of 9 months without pyrazinamide (2 months term health sequelae, including the risk of future TB
of ethambutol, rifampicin, and isoniazid; and 7 months recurrence and ongoing socioeconomic challenges even
of rifampicin and isoniazid) has been used.88 However, after being cured. Studies conducted among older adults
studies in Japan reported that pyrazinamide-containing reported decreased lung functions and higher severity of
TB regimens did not lead to significantly higher treat- COPD among TB survivors in the Republic of Ko-
ment discontinuation rates, liver toxicity, or death than rea.108,109 The risk of TB-related chronic lung disease is
regimens without pyrazinamide among older adults.89–91 highest in high TB burden countries and among ciga-
Nevertheless, even in the absence of pyrazinamide, the rette smokers.28 TB survivors also experience a signifi-
frequency of treatment-related adverse events was cantly increased risk of death compared to the general
generally higher in older adults with TB.92 Ethambutol, population post-treatment, with most deaths attributed
for instance, has been reported to be the most common to cardiovascular disease.110–113 TB and disabilities asso-
drug responsible for major adverse events (e.g., ciated with it may have multiple negative impacts on a
dermatologic, gastrointestinal, arthralgia, liver injuries, survivor’s quality of life114–116 and mental health, com-
and visual changes) among older adults in the Republic pounded by TB-associated stigma.117 Apart from direct
of Korea.93 Its potential effect on visual acuity should be health impacts, the socioeconomic implications of TB
considered in the presence of other age-related eye may also endure post-treatment completion. TB-affected
problems such as retinopathy and cataracts.31 Among households report ongoing income loss and lack of
second-line TB drugs,94 fluoroquinolone use among employment beyond TB treatment completion, which
older adults has been associated with a higher risk of also affects older adults in these households.118
hepatoxicity, tendinopathy, neuropsychiatric reactions,
and QT prolongation.95 There is a lack of safety and ef-
ficacy data on bedaquiline use in older adults,96 and the Key interventions in addressing TB among
use of linezolid (the third group A drug) has been older adults
associated with a higher risk of serious adverse events, TB transmission and infection management
particularly if used for longer periods.94 In general, there Testing for TB infection, disease monitoring, and infection
is a lack of safety data on linezolid among older control
adults.97,98 Most group B and C second-line TB drugs94 Pre-admission screening of risk factors for TB could
have also been reported to be either less tolerable facilitate early TB case finding.119 In Hong Kong SAR,
among older adults or to lack age-specific data.74,99 systematic screening of new admissions to the aged-care
Traditional, complementary, and herbal medicines facilities for TB infection using IGRA and for TB disease
are ubiquitously used in this region.100 A meta-analysis using chest X-rays, was highly cost-effective at
of randomised controlled trials in 2020 reported that US$19,712 and US$29,951 per quality-adjusted life-year
combination therapy of various traditional Chinese (QALY) gained; compared to TB screening using Gen-
medicines and standard TB treatment regimens had eXpert® MTB/RIF and no screening. Further to the
120
higher pulmonary lesion absorption and cavity closure screening of residents, environmental control measures
rates than the control group (standard anti-TB such as improved ventilation and selective use of ultra-
regimen).101 However, the evaluated studies lacked violet germicidal irradiation in aged-care facilities could
rigour and were poorly standardised. The use of con- reduce TB transmission risk.121 Given the risk of infec-
current herbal medicines is generally discouraged, given tion among residents and staff in aged-care facilities, it
their association with drug-induced liver injury.100 is critical to generate evidence and establish clear
Ironically, its use as a ‘liver protector’ is pervasive guidelines for TB infection and disease screening, as
among people on TB treatment, especially in China, well as ongoing TB disease monitoring in settings with
despite a lack of evidence to support the practice.102 high rates of TB infection. Minimum infection control
Further systematic evaluation is required. criteria require consideration, with regular reporting
and review of practices to limit TB disease and trans-
Poor adherence due to health issues and inadequate support mission risk.
TB treatment adherence is vital in ensuring a favourable
outcome. However, loss to follow-up103 and treatment TB preventive treatment (TPT)
adherence are often an issue among older adults due to Compared to isoniazid-monotherapy for 6–9 months,
poor health understanding and general disability, as well rifamycin-based combination TPT for 3–4 months has
as more frequent adverse events and drug–drug similar efficacy, lower risk of liver injury, and better
interactions.31,104–106 Cognitive impairment, mostly de- treatment adherence.122 Given that the risk of hepato-
mentia, has also been associated with poor adherence to toxicity associated with isoniazid use in older adults ≥65
TB treatment.107 All these factors justify additional and years remains a concern,59 4-month rifampicin mono-
tailored support to facilitate safe treatment completion.31 therapy, endorsed by the WHO for HIV-negative

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individuals,57 could provide a safer alternative for older other forms of immunocompromise has not been eval-
adults.123 While there is empirical evidence on TPT uated and requires more formal exploration.
administration, tolerability, and a TPT completion rate
(isoniazid and rifampin-based) of >80% among older Social protection
adults in the Republic of Korea,124 there remains a Social protection in the form of income replacement
paucity of data and specific guidance on TPT use in this and financial grants may reduce TB incidence and
population. The risk of adverse events associated with mortality in older adults.133 In Cambodia, the provision
TPT remains a concern (including the shorter of health equity funds to support the poor improved
regimen).125 Therefore, further assessments on ap- access to healthcare services and reduced the overall
proaches to systematically manage TB infection and medical financial burden.134 More specifically, the pro-
TPT in this population are necessary. vision of free TB services, prioritisation of the needs of
Older adults who might be eligible (e.g., at-risk groups high-TB risk groups, and reduction of out-of-pocket
such as immunocompromised or documented TB con- payments on healthcare under the universal health
tact) should be carefully assessed, tested for TB infection, coverage framework are critical to ensure those affected
and carefully monitored for adverse effects if TPT is by the disease have access to the required TB care and
initiated. Monitoring should extend beyond TPT admin- rehabilitation.135 Interventions are also required to
istration, and a TPT register should provide an overview reduce the risk of falling into poverty after a TB diag-
of the complete care cascade.126 If thorough risk-benefit nosis.136 It is noteworthy that progress toward UHC
assessments and emerging evidence recommend TPT differs by country and area in the region (UHC indices
to eligible older adults, timely and effective referrals and range from 33 in Papua New Guinea to 87 in Australia).
the integration of TB infection testing and treatment with Therefore, intensified efforts are required by individual
other health services for chronic diseases should be countries to develop a strong and more inclusive health
explored as a pathway to administer TPT effectively.127,128 systems for all, including those affected by TB.
It is important that the design of relevant policies and
programs should be evidence-based and adhere to the Active case finding
clinical standards for managing TB infection.126 Interventions to actively seek and diagnose TB disease
among older adults are more effective than traditional
TB diagnosis and detection passive case-finding (PCF).137 Targeted screening of spe-
Timely diagnosis cific risk groups (e.g., people with diabetes or a history of
WHO-approved NAATs are recommended as the initial TB) using chest radiography as a screening tool helps to
test of choice to diagnose TB given improved sensitivity detect previously undiagnosed patients among older
(compared to smear microscopy) and rapid turnaround adults.138–140 In Cambodia, the use of computer aided
time (∼2 h to perform the test) with simultaneous drug detection (CAD) has resulted in an increased yield of TB
resistance prediction.129 Therefore, increasing the avail- detection among older adults.141 Incorporating novel
ability and accessibility of NAATs could facilitate timely technology combining ultra-mobile digital chest radio-
diagnosis and treatment initiation. graphs and CAD is a promising area for further research
The incorporation of NAATs in the field, particularly and scale-up to improve TB detection. Community-based
for ACF, was feasible yet resource intensive. Their effi- active case-finding models that target older adults can be
ciency hinges on the availability of a comprehensive effective in settings with variable TB burden.141–143 The
laboratory and healthcare ecosystem such as workforce experience in the Republic of Korea and Cambodia
capacity, sample transportation, test results communi- demonstrated an increased TB yield among older adults
cations and follow-up.130 A lack thereof, especially in compared to expected case notification rates.141,143,144
under-resourced settings, could pose a challenge in Beyond older adults-specific approaches, community-
timely TB diagnosis and treatment.80 wide screening for TB using NAAT in high-incidence
Interventions should also be implemented to settings such as Viet Nam was also shown to lower the
improve the quality of sputum samples collected from prevalence and transmission of TB in the population as a
older adults, especially those who are frail. More inva- whole.145 Contact investigation in settings like the
sive approaches to obtain specimens from the respira- Philippines, where TB disease and infection are highly
tory system and early morning gastric aspirates could be prevalent among TB-exposed household members,
used, but the potential benefit should be weighed demonstrated the value of contact investigation for active
against the risks of more invasive procedures.35,131 case finding and prevention of future disease among
Among people living with HIV, lateral flow urine lip- individuals and affected families.146 However, its impact
oarabinomannan assay (LF-LAM) could be considered a on community transmission has not been demonstrated.
complementary tool to assist TB disease diagnosis, Furthermore, aged-care facilities could consider moni-
especially when sputum collection is impossible or toring and screening healthcare staff and institutionalised
disseminated disease is considered.132 LF-LAM’s poten- older adults for TB disease at regular intervals. Apart
tial value in older adults with immune senescence or from the major benefits of active case finding in high-risk

Personal View
groups, negative aspects related to potential stigma and improves knowledge, attitude, and beliefs regarding TB,
misdiagnosis should be considered as well.147 positively impacting TB treatment adherence and out-
comes.157,158 In China, a comprehensive system that
TB and healthcare services organisation and governance included health education and peer support groups
To improve the quality of healthcare for older adults, the improved the outcomes of older adults treated for TB.159
WHO has introduced a set of age-friendly healthcare
principles that seek to enhance the quality of life for the Improve digital literacy and access to virtual support
ageing population.61 The adoption of such a framework A more person-centred approach could also benefit from
through training in the core competencies of managing the innovative use of new technology. The use of tele-
geriatric conditions, enhancing the facility’s physical medicine, both synchronous (observed live through a
environment, reducing waiting times, introducing an video camera) and asynchronous (recorded and sent to
appointment system, and other service improvements treatment observers or health workers for documentation
should be considered to improve healthcare accessibility and verification), has been shown to be cost-effective and
for older adults.61 user-provider friendly in treatment observation.160–163 As
The decentralisation of TB services to primary health smartphone and mobile internet connectivity becomes
care was also instrumental in increasing access to health more accessible than before, the feasibility of technology-
services.62 In China, systematic screening of TB disease enabled solutions increases. This was demonstrated by
is done in tandem with the annual health screening the COVID-19-induced health crisis, where the adoption
offered to older adults at their local hospital free of of digital innovations allowed TB care to continue with
charge, increasing the efficiency of active TB case- minimal disruptions.164,165 Beyond direct observation and
finding.17,138,148,149 It has been estimated that the inclusion supervision, technological solutions such as electronic
of active TB case finding during annual health checks in medication monitoring devices could be implemented to
China would result in a 48% and 58% decline in TB support and monitor treatment adherence.166,167 However,
disease incidence and mortality, respectively.17 Beyond uptake of these technology-dependent approaches is
TB case finding, the integration of services also facili- likely less favourable among older adults.166 As technol-
tates screening for other diseases and risk factors, ogy adoption differs widely across the region, it is vital to
particularly co-morbid conditions like undernutrition, understand the contextual determinants of acceptability
cigarette smoking, diabetes, and excessive alcohol use.150 and access to new technology,168 as well as its uptake and
Such linkages encourage person-centred care and utility among older adults.
should improve clinical management for TB and other
diseases, with better overall health outcomes.150 Post-TB health and rehabilitation
Recognition of the long-term physical and mental health
TB treatment and adherence impacts of TB identifies a need to identify, manage and
Person-centred approaches to treatment monitoring, and prevent these ramifications.116 Post-TB rehabilitation should
support be guided by a careful assessment of ongoing physical and
Person-centred TB care models should include tailored psychological needs at the end of TB treatment.
interventions and comprehensive care plans that
improve adherence and limit loss to follow-up. These Better linkages between health services to assist in
may include customised treatment support that extends monitoring and follow-up
beyond directly observed therapy (DOT), as well as ed- Considering the growing population of people who have
ucation, social and psychological support for people with survived TB, better linkages between TB, non-
TB and their close family members.151 Facility-based communicable diseases, and social and psychological
treatment support requires TB patients to visit a support programs are essential.169 If required, post-TB care
health facility daily to administer medications, which should include follow-up visits with appropriate healthcare
can be challenging for older adults.152 Use of family or professionals to manage ongoing TB-related complica-
community treatment support has been associated with tions. Ideally, all older adults should have a regular medical
lower default rates,153 higher treatment success rates, follow-up to assess their general health after TB treatment
and reduced death compared with facility-based treat- completion, including the possibility of TB recurrence and
ment support.154,155 Better health services integration appropriate management of all co-morbidities.
would facilitate the monitoring of TB treatment and the
management of relevant co-morbidities, improving both Data on post-TB outcomes and care needs in older adults
the quality and efficiency of care.156 A better understanding of the severity, frequency, and
While social protection seeks to address the socioeco- risk factors of adverse post-TB health outcomes113,170 is
nomic risk factors for TB and facilitates access to health needed to inform potential interventions. The feasibility
care, a strong social support system is important to assist of conducting post-TB assessment under routine pro-
recognition of TB symptoms, early diagnosis and treat- grammatic conditions has been demonstrated in China,
ment completion. Studies have shown that social support and the experience could be adapted to other settings.171

Personal View
Future research adults with past infection, given that age-associated

Given the rapid growth of the ageing population in the immune dysfunction increases the risk of TB reac-
Western Pacific Region and the vulnerability of older tivation. Older adults exhibit atypical features of TB and
adults to TB, more research is required to generate the often present with multiple comorbidities, which may
evidence needed to better prevent and manage TB in this delay TB diagnosis, while their care-seeking behaviour
population. Table 2 provides an overview of key knowl- may be influenced by reduced mobility and more diffi-
edge gaps. As aged-care facilities are high-risk environ- cult interaction with the health care system. Existing
ments for TB transmission, the feasibility, effectiveness, comorbidities also complicate TB treatment, due to the
and cost-effectiveness of TB screening strategies among higher risk of adverse drug reactions and drug–drug
institutionalised older adults and their caregivers must be interactions. Post-TB sequelae and ongoing socioeco-
investigated. Beyond aged-care facilities, understanding nomic hardship may decrease the quality of life after TB
the access barriers and facilitators of TB service uti- treatment completion.
lisation among older adults is important to assist case Age-friendly healthcare infrastructure and services,
finding, treatment adherence and post-treatment follow- increased awareness of atypical TB manifestations, and
up. Understanding all risk factors associated with TB integration of TB case-finding strategies with comorbidity
diagnostic delay and poor treatment outcome is essential management may assist earlier case detection. Treatment
for improving care. For TB diagnosis, a key challenge is adherence and adverse event monitoring requires
developing an accurate non-sputum-based test. For TB increased vigilance and careful consideration of age-
treatment, shorter and safer regimens and more user- considerate technology. Effective infection control mea-
friendly approaches to treatment delivery and moni- sures and routine screening may reduce TB transmission
toring are needed. Further down the care cascade, the full risk, particularly in aged care facilities or other congregate
range of post-TB sequelae requires better description to settings.
enable tailored interventions and care plans for TB sur- Further research and innovation, as well as current
vivors. It is also important to consider broader issues best practices, should inform the formulation of policies
such as social protection and relevant ethical principles, and programmatic guidance to improve TB prevention,
with a particular need for more research in low-and- detection, and care practices among older adults.
middle-income countries that are also experiencing a Considering the Western Pacific Region’s rapidly ageing
demographic transition. population and the increasing TB burden observed
among older adults, it seems pertinent and timely to
develop a roadmap for TB care focussed on this
Conclusion population.
The TB burden is generally reduced in populations with
Contributors
increased life expectancy, mainly through improved T.I., B.J.M., K.R., F.M., K.H.O., K.V., C.W.M.O., S.K., H.K., Y.L., S.Y.,
socioeconomic conditions. However, the risk of TB H.T.G.T. conceptualised and designed the study. A.K.J.T. conducted the
disease in these settings may be increased among older literature search. B.J.M., C.W.M.O., L.K., F.M., K.V., K.R., M.Y.
Domains Priorities
Transmission and infection 1. Effectiveness and cost-effectiveness (including risk-benefit analysis) of TB infection testing and TPT for healthcare workers caring for older adults in
management nursing facilities or healthcare settings
Diagnosis and case-finding 2. Barriers and facilitators in access to and utilisation of health care, particularly TB services
3. Effectiveness and cost-effectiveness of TB screening strategies, including diagnostic tools and frequency, as well as safety of TPT, among institu-
tionalised older adults
4. Quantification of the time to TB diagnosis and treatment initiation
5. Risk factors for delayed care-seeking, diagnosis, and treatment initiation
6. Knowledge, awareness, and practices of healthcare providers on TB screening, detection, and diagnosis among older adults
7. Development of non-sputum-based TB diagnostics
8. Optimal coverage and breadth of social protection services for older adults
9. Ethics, equity, and human rights issues in TB among older adults
Treatment 10. Shorter and safer TB regimens for both TB infection and TB disease for the older adults
11. Effectiveness, cost-effectiveness, and implementation science of innovative approaches, including but not limited to the use of mobile digital
technologies and community engagement, in TB treatment administration (e.g., treatment support) and monitoring (adherence, adverse effects,
and outcomes) among older adults
Post-TB health and rehabilitation 12. Severity, frequency, risk factors, and costs of post-TB health, including psychological, and social sequelae
13. Effectiveness and cost-effectiveness of practices and interventions to improve post-TB health and wellbeing
14. Palliative and end-of-life care for older adults where TB cure is not feasible
TB; tuberculosis, TPT; TB preventive treatment.
Table 2: TB research domains and priorities in older adults.

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script. B.J.M., K.V., K.H.O., T.I., K.R., S.Y., C.W.M.O., S.K., T.Y., A.O., transmission among elderly persons, Yamagata Prefecture, Japan,
L.K., H.J.K., Y.L., M.Y., K.P., H.T.G.T. critically revised the manuscript. 2009–2015. Emerg Infect Dis. 2017;23:448–455.
14 Chee CBE, James L. The Singapore Tuberculosis Elimination
All authors contributed to the final version of the manuscript, reviewed,
Programme: the first five years. Bull World Health Organ.
and approved the manuscript. 2003;81(3):217–221.
15 Negin J, Abimbola S, Marais BJ. Tuberculosis among older adults–
Data sharing statement time to take notice. Int J Infect Dis. 2015;32:135–137.
All data included in this paper are available from the reference list. 16 Cruz-Hervert LP, García-García L, Ferreyra-Reyes L, et al. Tuber-
culosis in ageing: high rates, complex diagnosis and poor clinical
Declaration of interests outcomes. Age Ageing. 2012;41:488–495.
The authors declare that they have no competing interests. 17 Huynh GH, Klein DJ, Chin DP, et al. Tuberculosis control strate-
gies to reach the 2035 global targets in China: the role of changing
demographics and reactivation disease. BMC Med. 2015;13:88.
Acknowledgements 18 Morishita F, Viney K, Lowbridge C, et al. Epidemiology of tuber-
The authors wish to thank Dr Philippe Glaziou and Dr Ernesto Jaramillo culosis in the Western Pacific Region: progress towards the 2020
for their critical review of the research priorities. This project was fun- milestones of the end TB strategy. Western Pac Surveill Response J.
ded by 1) the World Health Organization Regional Office for the 2020;11:10–23.
Western Pacific, with financial contributions from the Government of 19 Mori T, Leung CC. Tuberculosis in the global aging population.
the Republic of Korea through the Korean Disease Control and Pre- Infect Dis Clin North Am. 2010;24:751–768.
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The funders did not play any role in the paper design, data collection, 22 Shaw AC, Joshi S, Greenwood H, Panda A, Lord JM. Aging of the
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prevalence. Gerontology. 1996;42:155–162.
Supplementary data related to this article can be found at https://doi.
24 Menon S, Rossi R, Nshimyumukiza L, Wusiman A, Zdraveska N,
org/10.1016/j.lanwpc.2023.100770. Eldin MS. Convergence of a diabetes mellitus, protein energy
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Tuberculosis in older adults: challenges and best practices in

Summary The Lancet Regional

Keywords: Tuberculosis; Aged; Policy

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Background where enhanced TB management has reduced TB

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Key challenges in addressing TB among older TB infection management

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Future research adults with past infection, given that age-associated

Table 2: TB research domains and priorities in older adults.

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