Risk TB
Risk TB
Risk TB
Background: The increasing global burden of tuberculosis (TB) is linked to human immunodeficiency virus (HIV) infection.
Methods: We reviewed data from notifications of TB
cases, cohort treatment outcomes, surveys of Mycobacterium tuberculosis infection, and HIV prevalence in patients with TB and other subgroups. Information was collated from published literature and databases held by the
World Health Organization (WHO), the Joint United Nations Programme on HIV/Acquired Immunodeficiency
Syndrome (UNAIDS), the US Census Bureau, and the US
Centers for Disease Control and Prevention.
Results: There were an estimated 8.3 million (5th-
UMAN immunodeficiency
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Formulas
Definitions
N = Population
2. P = tI and Ps = ts Is
P = Prevalence of TB Disease
3. Is /N = k
4. D = fI and Ds = fIs
IRR = TB Incidence Rate Ratio (TB Incidence Rate in Human Immunodeficiency Virus
[HIV]-Positive Persons/TB Incidence Rate in HIV-Negative Persons)
5. I = I +a + I a + In
or
I = m +a r +aN +a + m a r aN a + mnrnNn
m +r + I + /N +
6. IRR = a a = a a
m ar a I a /N a
7.
I +a
IRR (N +a /Na )
=
Ia I + (N +a /Na ) (IRR I)
A literature and database search was conducted for data on HIV prevalence in patients with TB (I a+ / I a ) that could be
matched with adult HIV prevalence (N a+ /
N a ) in the same region and time period. Equation 7 in Figure 1 (derived
from equation 6) relates these 2 sets of
data to IRR, which can then be estimated by maximum likelihood of fit.
Equation 6 makes it clear that IRR depends on both relative MTB infection
rates (m a+ / m a ) and rates of progression
to active disease (r a+ / r a ). Since relative
MTB infection rates are likely to vary
from country to country, as may progression rates, IRR is expected to vary,
too. 41 We attempted to identify regional IRR variations within limits set
by the quality of data.
9. D a = D +a f (I + I a )
+ = HIV Positive
TB Attributable to HIV
= HIV Negative
Figure 1. Formulas for estimating tuberculosis (TB) incidence, prevalence, and deaths.
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notified, but non-DOTS ones not necessarily so.37 Patients treated in the private sector, of whom many receive nonstandard drug regimens,42 are included
among non-DOTS patients.
In our estimation of the proportions of HIV-positive and HIV-negative patients with TB who received TB
treatment, the proportion of those who
received TB treatment was taken to
be independent of HIV status. This probably underestimated the proportion of
HIV-associated TB patients who were
left untreated in resource-poor settings.16-20,22-26
TB PREVALENCE AND
HIV-ASSOCIATED TB
TRANSMISSION
Estimates of TB prevalence were calculated from the product of incidence and
the estimated duration of illness (equation 2), as previously described.34 The exception was China, where the prevalence rate of smear-positive TB was
measured directly by a survey carried out
in 2000. We assumed that duration of illness differed when patients were smear
positive or smear negative, HIV infected
or not, treated through DOTS or other
programs, or untreated (Table 1).34
The point prevalence of active,
smear-positive disease is closely correlated with current TB transmission.53,70
We used the HIV-infected proportion of
prevalent smear-positive cases as a measure of the proportion of TB transmission events that were likely to be from
HIV-positive patients. This assumes that
the impact of HIV on TB infectivity is related to likelihood and duration of
smear-positive disease, but that infectivity per unit of time is independent of
HIV status.
TB DEATHS AND PROPORTION
ATTRIBUTABLE TO HIV
The number of TB deaths is the product
of incidence by the case fatality rate (CFR)
(equation 4). Tuberculosis deaths include those of patients who die without
ever being treated or while receiving treatment, as well as late deaths from relapse
or posttuberculous complications.
A literature search was conducted
for mortality during treatment; risk of TB
relapse and late complications; and autopsy series for the cause of death in patients with TB according to HIV status,
smear status, and regimen.47,48,56-69,71-84
These data, along with treatment results reported to WHO and revised country-specific estimates calculated for
1997,34 were used to estimate CFRs for
patients with TB.34 In nonindustrialized countries the estimated CFRs for pa-
Value
Range
References
60
6.0
41-77
3.5-8.0
43-46
10, 36, 39, 47-52
0.4-0.5
0.3-0.4
38
9, 34, 53
30-70
40-80
54, 55
54, 55
0.45
0.35
50
60
0.7
0.2
0.81
0.76
0.5
0.55-0.75
0.1-0.3
0.7-0.99
0.63-0.9
0.4-0.67
1.0
1.27
2.0
3.3
0.5-1.5
0.5-3
0.5-3
2-10
2.0
0.5
1.5-2.5
0.25-1
54, 56, 57
56, 58
59-62
59-62
63-66
48, 67-69
Assumed: no data
48, 69
Assumed: no data
54, 56, 57
59
Abbreviations: DOTS, the internationally recommended strategy for TB control; HIV, human
immunodeficiency virus; MTB, Mycobacterium tuberculosis; TB, tuberculosis.
*Parameters in this table are those used for all countries; parameters with values specific to different
countries or groups of countries are available at www.who.int/gtb/tbestimates or from the corresponding
author.
In industrialized countries, where risk of infection is falling steeply, infection prevalence was
estimated from surveys intead.
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between parameters that varied globally (ie, in the same way across different countries during each simulation)
and those that varied for each country
independently. Fifth and 95th centiles
were used as lower and upper bounds.
RESULTS
ESTIMATES OF REGIONAL
IRRs FOR TB
Paired HIV prevalence data from patients with TB and general populations were obtained from previous
publications,10,42,43,46-51,98,99 the US
Centers for Disease Control and Prevention,45,46 the HIV database kept
by the US Census Bureau,102 and
UNAIDS.36
Mostdatawerefromsub-Saharan
Africa, as shown in Figure 2A and
B. Data from countries outside Africa
being insufficient to permit IRR estimations for each WHO global region, we divided the remaining data
into data from nonindustrialized
countries outside Africa and data
from established market economies. Relevant data are shown in
Figure 2C and D. The average for 6
groups of developing countries (3 of
which are shown in Figure 2) was an
IRR of 5.9, with group averages ranging from 3.5 to 8.0. On this basis, we
have used an IRR of 6 for all nonindustrialized countries, with a range
of 3.5 to 8 for uncertainty analysis.
However, the choice of an IRR
of 6 greatly underestimates HIV
prevalence for TB patients in industrialized countries.42-44 We derived
a better IRR estimate of 60 for the
United States from national statistics on adult HIV prevalence and on
HIV prevalence in TB patients aged
25 to 44 years (Figure 2D, 1998
data).44,45 This estimate is the approximate midpoint of a lower
bound (IRR = 41) obtained by assuming that the 60% of TB patients
tested for HIV infection in 1998 included all those who were HIV infected, and an upper bound
(IRR=77) derived from the assumption that those tested were a representative sample of all patients with
TB.45 No other industrialized country monitors HIV prevalence in TB
patients systematically, but single nationally representative estimates of
HIV prevalence in TB patients have
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0.8
1.0
0.8
0.6
0.6
0.4
0.4
0.2
0.2
0
0
0.8
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.8
0.6
0.6
0.4
0.4
0.2
0.2
0.1
0.2
0.3
0.4
0.5
0.6
0
0
0.02
0.04
0.06
0.08
0.10
0.12
0.002
0.004
0.006
0.0008
Figure 2. Human immunodeficiency virus (HIV) prevalence in patients with tuberculosis (TB) vs HIV prevalence in the adult (15-49 years old) population. A,
Matched data where x and y variables were measured in the same study populations. B-D, Data were obtained from the same part of each country, but not
necessarily the same populations. A and B, African countries. C, Nonindustrialized countries outside Africa. D, 12 states of the United States. Black circles indicate
the weighted average for these states; open circles, lower and upper estimates of the national average of HIV prevalence in adult patients with TB; and , the
weighted average for the 12 states. Regression lines in A-D were obtained from the maximum likelihood estimate of incidence rate ratio derived by fitting equation
6 of Figure 1 to data represented by the points. This assumes that incidence rate ratio is constant for each region.
been published for the United Kingdom (3.3%)44 and Spain (15%).43
When paired with general population estimates for HIV (0.11% and
0.6%, respectively),36 these give IRRs
of 31 and 29, respectively. In the absence of better information we used
an IRR of 60 (range, 41-77), a ratio
based on US data, for all industrialized countries.
ESTIMATES
OF THE TB BURDEN AND
THE IMPACT OF HIV
Here we present an overview of the
TB burden that focuses on the impact of HIV. Statistics are given for the
world as a whole; for each of the 6
WHO regions (Table 2); and for
each of 22 high-burden countries with
the largest numbers of cases, which
together account for approximately
80% of the worlds new TB cases
(Table 3 and Figures 3, 4, and 5).
These 22 countries include 5 of the
15 countries with the highest incidence rates per capita (Figure 6). A
list of estimates for all countries, together with updates, can be found at
www.who.int/gtb/tbestimates, or
obtained from the corresponding
author.
There were an estimated 8.3 million (7.3-9.2 million) new TB cases
in 2000, or 137 (121-151) per 100000
population; 3.7 million (3.1-4.0 million) were smear positive, ie, 61 (5166) per 100000 population. Most new
cases were in adults aged 15 to 49
years (5.4 million; 172/100 000).
Among WHO regions, the African Region (essentially sub-Saharan Africa)
had by far the highest annual incidence rates (290/100000), while the
South-East Asian Region had the largest number of cases (3.0 million). Half
the new cases (4.4 million) were in
the top 5 countries, all in Asia. Of 15
countries with the highest incidence
rates per capita, 13 were in Africa
(Figure 6).
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Africa
Population, millions
New cases of TB, all forms
No. of cases, thousands
Incidence rate per 100 000 population
Change in incidence rate 1997-2000, %/y
Prevalence of HIV in new adult
cases (15-49 years old), %
Attributable to HIV, thousands
Attributable to HIV, % of adult cases
New smear-positive cases of TB
No. of cases, thousands
Prevalence rate of SS+ TB, per 100 000 population
Proportion of prevalence of SS+ cases infected with HIV, %
Infection prevalence among adults
Prevalence of MTB infection, %
Prevalence of MTB-HIV coinfection, %
Deaths from TB
Deaths from TB, thousands
Deaths from TB, per 100 000 population
Deaths from TB in HIV-positive adults,
thousands
Adult AIDS deaths due to TB, %
TB deaths attributable to HIV, %
640
Americas
Eastern
Mediterranean
Europe
South-East
Asia
Western
Pacific
Global
832
485
874
1536
1688
6053
1857
290
3.9
38
382
46
4.1
5.9
587
121
1.4
1.8
468
54
2.8
2.8
2986
194
1.3
3.2
2031
120
0.0
1.3
8311
137
0.4
11
421
31
12
5.1
5.2
1.5
8.2
2.6
53
2.7
13
1.1
511
9
785
185
7.5
169
27
1.0
264
103
0.2
210
35
0.5
1338
209
0.3
913
117
0.1
3679
122
1.4
31
2.7
15
0.1
27
0.1
14
0.0
46
0.3
32
0.0
30
0.4
482
75
203
55
6.6
3.9
135
28
3.0
72
8.3
1.6
12
39
4.1
6.5
11
2.0
10
2.1
727
47
29
8.1
3.7
368
22
5.7
1839
30
246
17
1.4
11
12
Abbreviations: AIDS, acquired immunodeficiency syndrome; HIV, human immunodeficiency virus; MTB, Mycobacterium tuberculosis; SS+, smear-positive
sputum; TB, tuberculosis; WHO, World Health Organization.
Assuming lifelong MTB infection, and excluding effects on transmission of the recent increases in incidence in Africa and the former
Soviet Union, 30% of the world
population (1.8 billion people) carried MTB in 2000. Assuming no
shared risk factors, the prevalence of
MTB-HIV coinfection among adults
aged 15 to 49 years was 0.36%, or
11.4 million people. Coinfection
prevalence in adults aged 15 to 49
years equaled or exceeded 5% in 8
countries, all on the African continent. The largest numbers of coinfected adults were in South Africa
(2.0 million), India (1.7 million),
and Nigeria (0.9 million).
COMMENT
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India
South Russian
China Indonesia Bangladesh Nigeria Pakistan Philippines Africa Federation Ethiopia
Population, millions
1009
1275
New TB cases, all forms
No. of cases, thousands
1816
1437
Incidence rate per 100 000
180
113
population
Change in incidence rate
1.3
0.0
1997-2000, %/y
HIV prevalence in new adult
4.0
0.4
cases (15-49 years old), %
Attributable to HIV, thousands
41
3.1
Attributable to HIV, % of adult
3.4
0.4
cases
New smear-positive cases of TB
No. of cases, thousands
813
646
Prevalence rates of SS+ TB,
201
122
per 100 000 population
Prevalence of SS+, HIV-positive
0.6
0.1
cases, %
Infection prevalence among adults
Prevalence of MTB infection, %
46
31
Prevalence of MTB-HIV
0.3
0.0
coinfection, %
Deaths from TB
Deaths from TB, thousands
453
268
Deaths from TB per 100 000
45
21
population
Deaths from TB in HIV-positive
24
1.4
adults, thousands
Adult AIDS deaths due to TB, %
10
8.6
TB deaths attributable to HIV, %
4.8
0.5
Democratic
Republic
of Congo
212
137
114
141
76
43
145
63
51
582
274
325
237
261
230
245
173
230
304
220
509
183
126
178
284
150
294
1.3
1.3
0.3
0.1
0.8
0.2
0.2
0.1
261
325
2.4
146
214
1.5
1.0
24
0.6
0.4
60
1.0
42
24
38
20
0.7
0.5
0.5
0.3
80
50
1.1
0.9
45
35
22
20
75
186
65
185
113
192
110
181
104
232
0.0
0.0
4.5
0.1
0.1
52
0.0
46
0.0
36
1.8
37
0.0
52
0.0
79
57
76
67
65
46
44
58
146
69
8.7
5.9
90
219
82
88
21
42
8.3
60
139
2.9
2.9
0.3
9.5
5.8
12
0.0
27
2.8
36
1.8
33
23
47
74
36
70
0.5
0.1
23
0.5
0.2
38
0.4
21
11
18
0.3
13
0.1
11
28
8.0
0.7
23
0.5
18
59
35
1.2
10
41
15
28
United
Republic of
Vietnam Kenya Tanzania Brazil Thailand Myanmar Zimbabwe Uganda Cambodia Afghanistan Mozambique
Population, millions
New TB cases, all forms
No. of cases, thousands
Incidence rate, per 100 000
population
Change in incidence rate
1997-2000, % / y
HIV prevalence in new adult
cases, %
Attributable to HIV, thousands
Attributable to HIV, % of adult
cases
New smear-positive cases of TB
No. of cases, thousands
Prevalence rates of SS+ TB,
per 100 000
Prevalence of SS+ HIV-positive
cases, %
Infection prevalence among adults
Prevalence of MTB infection, %
Prevalence of MTB-HIV
coinfection, %
Deaths from TB
Deaths from TB, thousands
Deaths from TB, per 100 000
population
Deaths from TB in HIV-positive
adults, thousands
Adult AIDS deaths due to TB, %
TB deaths attributable to HIV, %
78
31
35
170
63
48
13
23
13
22
18
143
183
138
449
117
335
114
67
86
137
78
164
76
604
75
323
75
573
69
319
48
262
1.0
14
1.4
49
35
1.0
1.2
41
41
25
29
57
253
50
207
64
96
0.5
3.9
1.3
1.3
3.3
12
11
1.8
2.8
5.1
10
51
46
38
101
4.8
9.1
35
115
3.9
0.3
0.0
48
31
56
16
29
7.7
17
0.0
0.0
14
40
31
282
32
187
2.5
33
2.7
19
0.1
43
0.9
41
0.8
35
115
27
77
15
8.8
13
21
19
40
0.3
19
11
0.6
1.8
2.6
9.7
7.9
12
1.6
12
48
11
36
3.2
3.4
3.0
12
6.2
13
7.5
53
8.1
38
21
20
5.0
16
130
34
548
20
124
3.5
0.0
15
1.3
76
3.1
56
0.0
25
3.3
20
92
13
70
19
82
16
121
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31
310
9.1
1.0
20
2.5
19
24
1.5
35
0.7
23
3.2
2.0
67
8.4
44
0.1
13
2.8
3.6
30
21
15
0.0
6.8
0.0
0.0
9.8
49
Ranges
<1000
1000-9999
10 000-99 999
100 000-999 999
100 000
No Estimate
Ranges of Rates
(per 100 000 Population)
<1
1-9
10-99
100-199
200
No Estimate
Figure 4. Estimated numbers of human immunodeficiency virusinfected tuberculosis cases per 100 000 population (all ages) by country in 2000.
clearly a major burden for these countries, many of which are in Africa.
Our results indicate that the HIV
epidemic is exacerbating TB transmission, although on a case-by-case
basis disproportionately few infections come from HIV-infected patients. This is because TB patients with
HIV are less likely to be smearpositive than patients without HIV,
and the duration of infectiousness is
relatively brief in them because they
have a relatively rapid progression of
disease. Our results in this respect are
qualitatively consistent with those of
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Ranges, %
<1
1-9
10-19
20-49
50
No Estimate
Figure 5. Proportions of adult tuberculosis cases attributable to human immunodeficiency virus by country in 2000.
14
All TB
TB With HIV Infection
800
10
14
600
3
8
3
400
6
1
200
i
a
e
a
o
ca
ut
nd
bia
dia
th
ibi
an
bw
fri
ila
m
m
bo
ibo
so
ba
az
tsw
Za
m
hA
Dj
Le
Na
t
m
a
i
u
Bo
Sw
C
Z
So
a
ny
Ke
a
wi
ali
ala
m
M
So
iti
e
ia
on
an
Le
nz
Ta
ra
r
f
e
Si
co
bli
pu
e
dR
ite
Un
Ha
Figure 6. Fifteen countries with the highest estimated tuberculosis (TB) incidence rates per capita (all
ages) and corresponding incidence rates of human immunodeficiency virus (HIV)infected TB. Numbers
above the bars are percentages of Mycobacterium tuberculosisHIV coinfection.
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Estimated TB Incidence
per 100 000 Population
1000
800
600
400
200
0
0
10
20
30
40
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4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
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