Epidemiology of Tuberculosis and HIV Coinfections in Singapore, 2000 2014

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DOI: 10.1111/hiv.

12529
2017 British HIV Association HIV Medicine (2017)
SHORT COMMUNICATION

Epidemiology of tuberculosis and HIV coinfections in


Singapore, 2000 2014
K Nandar,1 LW Ang,1 J Tey,1 L James,1 KM Kyi Win,2 CBE Chee,2 OT Ng,2 JL Cutter1 and YT Wang2
1
Ministry of Health, Singapore, and 2Tan Tock Seng Hospital, Singapore

Cross-matching of records between Singapores tuberculosis and HIV registries showed that 3.3%
of individuals with tuberculosis (TB) were coinfected with HIV (2000 2014), the TB incidence
among individuals with HIV infection was 1.65 per 100 person-years, and 53% of coinfections
were diagnosed within 1 month of each other. The findings supported joint prevention
programmes for early diagnosis and treatment.
Keywords: coinfection, demography, HIV infections, registries, Singapore, tuberculosis
Accepted 3 May 2017

Introduction HIV/AIDS cases are notified to the National Public


Health Unit of the Ministry of Health (MOH). HIV screen-
Tuberculosis (TB) and HIV pose a dual epidemic threat ing is performed using enzyme immunoassays or rapid
to global health [1]. Trends of these two diseases in diagnostic tests, followed by a confirmatory western blot
Singapore indicate that TB and HIV coinfection poses a test for positive results.
potential public health threat. The TB incidence rate in Both registries contain information on demographics,
Singapore residents has markedly declined in the past such as age at diagnosis, gender, ethnicity, occupation,
decades, and is the lowest rate among South-East Asian country of birth and year of immigration to Singapore.
countries [2]. However, it is still much higher than that The TB registry tracks the progress and treatment out-
in many developed countries [3]. The HIV prevalence come of each case, while the HIV registry captures CD4
among Singaporean adults ( 15 years old) in 2014 was cell counts, stage of HIV infection at diagnosis and mode
0.15% [4] compared to 0.3% and 0.1% in the South- of HIV detection.
East Asia and Western Pacific regions, respectively [5]. Our study received ethics approval from the Singapore
In our study, we describe the demographic and clinical National Healthcare Group Domain Specific Review Board
characteristics of TB and HIV coinfections in Singapore, (NHG DSRB reference number 2015/00702). We retro-
and discuss the implications related to public health pol- spectively matched records between the HIV registry from
icy and disease surveillance. 1985 to 2014 and the TB registry from 2000 to 2014. For
TB cases with more than one notification, the first
Methods episodes were included in the study. The date of TB diag-
nosis is the earliest of the following dates: date treatment
In Singapore, TB and HIV are notifiable under the Infec- started, registration date, date of first positive smear, and
tious Diseases Act. All suspected and confirmed TB cases date of first positive culture.
are notified to the national TB registry within 72 hours This study was confined to Singapore citizens and per-
of starting TB treatment and/or receiving laboratory con- manent residents. We defined TB and HIV coinfections as
firmation by acid-fast bacillus smear followed by cases where the patient was diagnosed with HIV infection
mycobacterial culture [2]. First-line drug-susceptibility within 1 year of TB diagnosis, or diagnosed with HIV infec-
testing (DST) (i.e. susceptibility to streptomycin, rifampi- tion followed by TB. Of 798 matched records, 34 TB cases
cin, isoniazid and ethambutol) is performed for positive in which the patient had an HIV diagnosis > 1 year after
TB isolates. Isolates resistant to isoniazid and/or rifampi- TB diagnosis were excluded; none of them had multi-drug-
cin are subjected to second-line DST. resistant TB (MDR-TB), i.e. resistance to both rifampicin
and isoniazid. Data analysis was confined to 764 coinfected
cases. The TB incidence density rate (IDR) was defined as
the number of TB cases occurring per 100 person-years of
Correspondence: Dr Khine Nandar, Ministry of Health, 16 College Road,
Singapore 169854. Tel: +65 6325 5679; fax: +65 6325 4679; e-mail: observation with follow-up censored at TB diagnosis, death
[email protected] or 31 December 2014, whichever was the earliest date.

1
2 K Nandar et al.

A chi-square test or Fishers exact test was used to cases with TB, respectively (P = 0.088). The proportion of
analyse differences between groups where appropriate. cases with MDR-TB was significantly higher in coinfected
SPSS software, version 23 (IBM Corp., Armonk, NY, USA) cases (0.9%) than in non-HIV-infected TB cases (0.4%)
was used for statistical analyses. A P-value < 0.05 was (P = 0.04) (Table 1).
considered statistically significant. Between 1985 and 2014, a total of 6685 cases of HIV
infection were reported; 603 of them had a TB diagnosis
on the same day or later, giving a TB IDR of 1.65 per
Results 100 person-years. The proportion of coinfections among
Between 2000 and 2014, a total of 23 150 TB cases HIV-infected cases was highest in 2001, at 24.1%, and
(15 259 laboratory confirmed and 7891 clinically diag- thereafter it declined continuously to 5.9% in 2014 (test
nosed) were reported, of which 764 (3.3%) were HIV posi- for trend, P < 0.0005).
tive (annual range, 2.6 4.7%) (Fig. 1). Adults aged Compared with non-TB infected HIV cases, TB and
between 30 and 49 years contributed 55.5% of coinfec- HIV-coinfected cases were significantly more likely to
tions, while men and Chinese contributed 94.1% and have advanced HIV infection and a CD4 count
82.1%, respectively. Younger age, male gender, Chinese < 200 cells/lL. They were more likely to have an HIV
ethnicity and being Singapore-born were significantly diagnosis through medical care and screening than non-
associated with coinfection (all P < 0.0005) (Table 1). TB infected HIV cases (82.1% versus 69.6%, respectively)
About half (52.5%) of coinfected cases had both infec- and to have been infected via heterosexual contact
tions diagnosed within 1 month; 49.5% had only pul- (79.3% versus 56.5%, respectively) and injecting drug use
monary TB; and 95.3% were newly diagnosed with TB. (4.6% versus 1.4%, respectively) (all P < 0.0005)
Compared with non-HIV-infected cases with TB, TB and (Table 1).
HIV-coinfected cases were more likely to have extrapul-
monary TB (EPTB) or both pulmonary and extrapul-
Discussion
monary TB, and a higher proportion were newly
diagnosed with TB (all P < 0.0005). About 29.7% of EPTB Our study is one of the first in South East Asia to report
cases were laboratory confirmed. The lymphatic system TB and HIV coinfections by cross-matching 15 years of
and pleura were the most common sites of infection in data from two national registries [6,7]. The proportion of
coinfected cases with EPTB and non-HIV-infected cases coinfections (2.9%) among TB cases between 2012 and
with EPTB, respectively. First-line DSTs were conducted 2014 was lower compared with that of countries in Asia
in 650 TB and HIV-coinfected cases and 16 358 non- with a high TB burden [8]. No particular trend in the
HIV-infected cases with TB in whom Mycobacterium annual proportion of coinfections was observed. The
tuberculosis complex (MTC) was detected, and resistance overall TB IDR among HIV-infected patients, at 1.65 per
to isoniazid without rifampicin resistance was detected in 100 person-years, was similar to that reported in the
3.8% and 2.7% of coinfected cases and non-HIV-infected Asia-Pacific region (1.98 per 100 person-years) [9].

Fig. 1 Tuberculosis (TB) incidence per 100 000 population and proportion of TB and HIV coinfections by year of TB notification in Singapore,
2000 2014.

2017 British HIV Association HIV Medicine (2017)


TB/HIV coinfections in Singapore 3

Table 1 Characteristics of tuberculosis (TB) and HIV-coinfected cases, non-HIV-infected TB and non-TB-infected HIV cases in Singapore

TB and HIV-coinfected Non-HIV-infected TB Non-TB-infected HIV


cases (n = 764) cases (n = 22 386) cases (n = 5921)
Characteristic n (%) n (%) n (%)

Gender
Male 719 (94.1) 15 578 (69.6) 5357 (90.5)
Female 45 (5.9) 6808 (30.4) 564 (9.5)
Ethnic group
Chinese 627 (82.1) 16 185 (72.3) 4643 (78.4)
Malay 101 (13.2) 4218 (18.8) 790 (13.3)
Indian 26 (3.4) 1376 (6.2) 300 (5.1)
Other 10 (1.3) 607 (2.7) 188 (3.2)
Time of TB diagnosis
Before HIV diagnosis
1 12 months 47 (6.2)
< 1 month 114 (14.9)
After HIV diagnosis
< 1 month* 287 (37.6)
1 3 months 46 (6.0)
4 6 months 26 (3.4)
7 12 months 27 (3.5)
13 24 months 36 (4.7)
25 48 months 60 (7.9)
> 48 months 121 (15.8)
All TB cases
Age at TB diagnosis
0 9 years 1 (0.1) 164 (0.7)
10 19 years 0 (0.0) 650 (2.9)
20 29 years 35 (4.6) 1928 (8.6)
30 39 years 151 (19.8) 2536 (11.3)
40 49 years 273 (35.7) 3607 (16.1)
50 59 years 167 (21.9) 4347 (19.4)
60 years 137 (17.9) 9154 (40.9)
Period of TB notification
20002002 156 (20.4) 4818 (21.5)
20032005 142 (18.6) 4342 (19.4)
20062008 166 (21.7) 4113 (18.4)
20092011 167 (21.9) 4581 (20.5)
20122014 133 (17.4) 4532 (20.2)
Born in Singapore
Yes 726 (95.0) 18 535 (82.8)
No 38 (5.0) 3851 (17.2)
Clinical characteristics
Site of disease
Pulmonary alone 378 (49.5) 17 656 (78.9)
Extrapulmonary alone 131 (17.1) 2933 (13.1)
Both pulmonary and extrapulmonary 255 (33.4) 1797 (8.0)
Category of TB
New 728 (95.3) 20 625 (92.1)
Relapse 36 (4.7) 1761 (7.9)

TB and HIV-coinfected Non-HIV-infected cases


cases (n = 650) with TB (n = 16 358)
n (%) n (%)

Patients with TB with MTC detected


Drug resistance
INH but not RMP 25 (3.8) 446 (2.7)
INH and RMP 6 (0.9) 65 (0.4)
RMP but not INH 4 (0.6) 23 (0.1)
Other drugs 21 (3.2) 463 (2.8)

2017 British HIV Association HIV Medicine (2017)


4 K Nandar et al.

Table 1 (Continued )

TB and HIV-coinfected Non-HIV-infected TB Non-TB-infected HIV


cases (n = 764) cases (n = 22 386) cases (n = 5921)
Characteristic n (%) n (%) n (%)

All HIV-infected patients


Age at HIV diagnosis
0 9 years 1 (0.1) 30 (0.5)
10 19 years 3 (0.4) 68 (1.2)
20 29 years 60 (7.9) 1080 (18.2)
30 39 years 173 (22.6) 1802 (30.4)
40 49 years 242 (31.7) 1508 (25.5)
50 59 years 162 (21.2) 902 (15.2)
60+ years 123 (16.1) 531 (9.0)
Period of HIV notification
19851999 82 (10.7) 1054 (17.8)
20002002 151 (19.8) 546 (9.2)
20032005 135 (17.7) 735 (12.4)
20062008 147 (19.2) 1091 (18.4)
20092011 117 (15.3) 1248 (21.1)
20122014 132 (17.3) 1247 (21.1)
Stage of HIV diagnosis
Not late stage 202 (26.4) 3057 (51.6)
Late stage 562 (73.6) 2864 (48.4)
Baseline CD4 count
< 50 cells/lL 177 (23.2) 1121 (18.9)
50 199 cells/lL 161 (21.1) 872 (14.7)
200 500 cells/lL 76 (9.9) 1367 (23.1)
> 500 cells/lL 19 (2.5) 422 (7.1)
Unknown 331 (43.3) 2139 (36.1)
Mode of HIV detection
Medical care and screening 627 (82.1) 4120 (69.6)
Own request 33 (4.3) 733 (12.4)
Contact tracing 24 (3.1) 283 (4.8)
Prisons/Drug Rehabilitation Centre/halfway house 34 (4.5) 209 (3.5)
Life insurance 12 (1.6) 120 (2.0)
Blood donation 6 (0.8) 104 (1.7)
Other 20 (2.6) 318 (5.4)
Unknown 8 (1.0) 34 (0.6)
Mode of HIV transmission
Heterosexual 606 (79.3) 3346 (56.5)
Homosexual/bisexual 105 (13.7) 2274 (38.4)
Injecting drug use 35 (4.6) 81 (1.4)
Blood transfusion 0 (0.0) 3 (0.1)
Renal transplant overseas 0 (0.0) 5 (0.1)
Perinatal (mother to child) 1 (0.1) 30 (0.5)
Uncertain 17 (2.2) 182 (3.1)

INH, isoniazid; MTC, Mycobacterium tuberculosis complex; RMP, rifampin.


*Includes 56 patients diagnosed with TB and HIV on the same day.

The patient category is defined as follows: new, patient who never previously received treatment for > 1 month; relapse, patient who previously com-
pleted treatment or was treated and declared cured prior to developing active TB again.

Late-stage HIV infection was defined as having a CD4 count of < 200 cells/lL or developing AIDS-defining opportunistic infections at first diagnosis
or within 1 year after HIV diagnosis.

The proportion of coinfections among HIV cases plum- Singapore-born residents constituted the vast majority
meted from 24.1% in 2001 to 5.9% in 2014. In the same of coinfected cases, unlike some Europe countries where
period, among all coinfections, the annual proportion of foreign-born individuals have played an increasingly
coinfections diagnosed within 1 month of each other important role in the TB and HIV coinfection epidemiol-
increased, while that of cases having a TB diagnosis more ogy [10,11]. However, a local study reported increases in
than 1 month after an HIV diagnosis decreased. These the number and proportion of foreign-born individuals
findings suggest that the significant decline in the pro- with TB among long-term pass holders and permanent
portion of coinfections among HIV-infected patients residents between 2000 and 2009 [12]. The impact of TB
could be attributable to early HIV diagnosis and highly epidemiology on TB and HIV coinfections should be
active antiretroviral therapy (HAART). monitored closely.

2017 British HIV Association HIV Medicine (2017)


TB/HIV coinfections in Singapore 5

More than a third (39.8%) of coinfected patients were Health Unit, Ministry of Health, Singapore for providing
aged 50 years, and these patients were reported to have HIV data and cross-matching the data from the two reg-
lower CD4 counts at HIV diagnosis and a higher rate of istries, and the Policy and Control Branch, Communicable
active TB, and were more likely to have adverse clinical Diseases Control Division, Ministry of Health, Singapore for
outcomes [13,14]. Our findings reinforce the need to their input on policies and measures for prevention and
increase HIV awareness and improve prevention measures control of TB and HIV infections in Singapore.
and screening services in this older age group. Funding: This research did not receive any specific
About half of coinfected patients (53%) had diagnoses grant from funding agencies in the public, commercial,
of TB and HIV infection within 1 month of each other. or not-for-profit sectors.
At the Tuberculosis Control Unit (TBCU), where nearly
70% of all Singapore residents with TB undergo treat-
ment, more than 90% of patients with TB were screened
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2017 British HIV Association HIV Medicine (2017)

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