Tuberculosis (TB)

Results

Monitoring progress in TB control

Countries reporting to WHO

By the end of 2006, 199 of 212 countries and territories reported case notifications for 2005 and/or treatment outcomes for patients registered in 2004 (Annex 2). These countries include 99.9% of the world’s population. Reports were submitted by all 22 HBCs. The countries that did not report included 10 Caribbean islands, Equatorial Guinea, Monaco and San Marino.

Case notifications and incidence estimates

The 199 countries reporting to WHO notified 5.1 million new and relapse cases, of which 2.4 million (47%) were new smear-positive cases (Table 8; Figure 1). Of these notifications, 4.9 million were from DOTS areas, including 2.3 million new smear-positive cases. A total of 26.5 million new and relapse cases, and 13.0 million new smear-positive cases, were notified by DOTS programmes between 1995 and 2005. Based on surveillance and survey data, we estimate that there were 8.8 million new cases of TB in 2004 (136 per 100 000), including 3.9 million (60 per 100 000) new smear-positive cases (Table 9; Figures 2, 3).

Comparing different parts of the world, the African Region (23%), South-East Asia Region (35%) and Western Pacific Region (25%) together accounted for 83% of all notified new and relapse cases and similar proportions of new smear-positive cases in 2005. Because DOTS has emphasized diagnosis by sputum smear microscopy, 48% of all new and relapse cases were new smear-positive (approximately 45% expected) in DOTS areas, compared with 36% elsewhere. Among new pulmonary cases reported by DOTS programmes, 59% were new smear-positive (a minimum of 65% expected), compared with 46% elsewhere (Table 8). The proportion of smear-positive cases among pulmonary cases reported under DOTS conforms with expectations and so, therefore, does the proportion of smear-negative cases.

In ranking countries by the estimated number of incident cases, 22 countries have been given special attention (Table 8). The magnitude of the TB burden within countries can also be expressed as the incidence rate per 100 000 population. Among the 15 countries with the highest estimated TB incidence rates, 12 are in Africa (Figure 4). The high incidence rates estimated for the African countries in this list are partly explained by the relatively high rates of HIV coinfection. Where HIV infection rates are higher in adult populations, they are also estimated to be higher among new TB patients. Figure 5 maps the distribution of HIV among TB patients, showing the relatively high rates in countries of eastern and southern Africa (subregion African – high HIV). Some countries have small populations but high rates of HIV infection; in Swaziland, for example, 75% of TB patients were estimated to be HIV-positive in 2005. Figure 6 shows how the number of HIV-infected TB patients varies among countries and regions. South Africa, with 0.7% of the world’s population, had 19% of all cases of TB in adult HIV-positive people in 2005, while 10% of cases lived in India. The rest of the African Region accounted for a further 61% of HIV-infected TB cases in 2005.

Using the time series of notifications of all TB cases from countries thought to have reliable data, and scaling by the estimated rates of case detection, we have estimated the trends in TB incidence (all forms of TB) for nine epidemiologically different subregions of the world (subdivisions of the six WHO regions) for the period 1990 to 2005 (Figure 7). In six of the nine subregions the incidence rate was stable or falling for most of this period. In subregions Africa – high HIV and Eastern Europe, incidence rates increased for most of the period since 1990 but now appear to have stabilized or begun to fall.

In subregion Africa – high HIV, the annual change in TB incidence runs almost parallel to the change in HIV prevalence. Since 1990, both HIV prevalence and TB incidence have been increasing more slowly each year and, by 2005, both indicators were falling (rates of change negative; Figure 8). The time series of estimates for some African countries show the expected lag between peak HIV prevalence and peak TB incidence rate. In Zimbabwe, for example, estimated HIV prevalence reached a maximum in 1997, while the TB case notification rate was highest in 2002.

In subregion Africa – low HIV, the TB incidence rate was evidently still increasing in 2005. In eastern Europe, the annual increase in the incidence rate reached nearly 20% in 1995 but had stabilized by year 2000.

The global incidence rate of TB peaked around 2002 and appears now to have stabilized or begun to decline (Figure 7). The incidence rate is now stable or falling in all six WHO regions. However, the slow decline in incidence rates per capita is offset by population growth. Consequently, the number of new cases arising each year is still increasing globally and in the WHO regions of Africa, the Eastern Mediterranean and South-East Asia.

DOTS coverage

The total number of countries implementing DOTS increased steadily from 1995 but had stabilized at about 180 by 2002, rising a little closer to the maximum in 2005 (187 out of 212; Figure 9). All 22 HBCs have had DOTS programmes since 2000; many of which have been established for much longer. DOTS coverage within countries has steadily increased since 1995 (Figure 10; Table 10). By the end of 2005, 89% of the world’s population lived in counties, districts, oblasts and provinces of countries that had adopted DOTS. Geographical coverage was reported to be more than 80% in all regions except Europe (Figure 11).

All but four HBCs had at least 90% of the population living in areas where DOTS has been implemented. Population coverage in the remaining four – Afghanistan, Brazil, Nigeria, and the Russian Federation – was 81%, 68%, 65%, and 83% respectively.

Case notification and case detection

A total of 4.8 million new cases of TB were notified from all sources in 2005 represents 55% of the 8.8 million estimated new cases; the 2.4 million new smear-positive cases notified account for 62% of the 3.9 million estimated (Tables 8, 9; Annex 2).

The detection rate of new smear-positive cases from all sources increased slowly and linearly from 1995 to 2001 and then more quickly from 2002 to 2005 (Figure 12a). The increase from 2002 to 2005 is attributable mostly to increases in the numbers of new smear-positive cases reported in the South-East Asia and Western Pacific regions. The detection rate of all new TB cases, from DOTS and non-DOTS programmes, remained approximately stable from 1995 to 2001 but increased between 2002 and 2005 (Figure 12b).

DOTS programmes detected an estimated 53% of all new cases and 60% of new smear-positive cases in 2005. The detection rate achieved by DOTS programmes, of both smear-positive and all new TB cases, has accelerated sharply since 2000, rising more quickly than the overall (DOTS and non-DOTS) case detection rate (Figure 12). However, the increase in the smear-positive case detection rate under DOTS is slowing: the increment between 2004 (54%) and 2005 (60%) was 7%, which is less than in the two preceding yearly intervals (Table 11, Figure 12).

The point estimate of 60% smear-positive case detection rate by DOTS programmes in 2005 is below the 70% target. There is, however, much uncertainty surrounding this estimate: 95% confidence limits range from 52% to 69%, with a small chance (0.7%) of the true estimate lying at ≥70%.

Since case detection under DOTS has increased faster than the overall rate of case detection, the proportion of all notified new smear-positive cases that were notified by DOTS programmes has increased, reaching 97% in 2005. Almost all TB cases (96%) reported to WHO in 2005 were reported by DOTS programmes (Table 8).

The case detection rate within DOTS areas (measured by the ratio of case detection to population coverage) changed little between 1995 and 2001, averaging 51% worldwide, but had increased to 67% by 2005 (Figure 13). Data from the 22 HBCs show the same pattern of change, where recent increases since 2000 have been driven mainly, but not exclusively, by improvements in Asia: Bangladesh, China, India, Indonesia, Myanmar and the Philippines (Tables 10, 11; Figure 13; Annex 1).

Comparing the WHO regions, new smear-positive case detection rates by DOTS programmes in 2005 were lowest in the European (35%) and Eastern Mediterranean regions (44%) and highest in the Region of the Americas (65%), the South-East Asia Region (64%) and the Western Pacific Region (76%; Table 11, Figure 14). Only the Western Pacific Region met the 2005 target. In the three regions with the highest rates of case detection – South-East Asia, the Americas and the Western Pacific – the increment between 2004 and 2005 was smaller than in the preceding year. Among the HBCs, the deceleration in case detection was most conspicuous in India.

The Region of the Americas and the European Region reported the largest numbers of cases from outside DOTS programmes. Counting all smear-positive cases, the case detection rate in the Region of the Americas exceeded 70% (Table 11, Figure 15a). Counting all new cases, the overall case detection rate in Europe was 68% (Figure 15b).

Estimates of the case detection rates for individual countries suggest that 67 countries met the 70% target by the end of 2005. Of the additional new smear-positive cases reported by DOTS programmes in 2005 (compared with 2004), 39% were in China and 17% were in India (Figure 16). China and India have made big improvements in case detection in recent years, but these two countries still accounted for an estimated 28% of all undetected new smear-positive cases in 2005. However, in 2005, Nigeria had succeeded China as the second largest reservoir of undetected cases. These three countries are among eight that together accounted for 59% of all cases not detected by DOTS programmes in 2005 (Figure 17).

Outcomes of treatment

More than two million new smear-positive cases were registered for treatment in DOTS programmes in 2004, approximately the same number that were notified that year (Table 12). Discrepancies between the numbers of cases notified and registered for treatment were small globally, by region and for most HBCs. The largest proportional difference between notified and registered cases was reported by the Russian Federation.

The cure rate among cases registered under DOTS worldwide was 77%, and a further 7% completed treatment (no laboratory confirmation of cure), giving a reported, overall treatment success rate of 84%, i.e. 1% below the 85% target set for the 2004 cohort (evaluated by the end of 2005; Table 12). An estimated 46% of all smear-positive cases arising in 2004 were treated successfully by DOTS programmes. Of all patients treated under DOTS, 10% had no reported outcome (defaulted, transferred, not evaluated). Treatment results for 11 consecutive cohorts (1994–2004) of new smear-positive patients show that the success rates have been 80% or more in DOTS areas since 1998, even though the number of patients has increased from 240 000 in 1994 to over 2 million in 2004 (Tables 12, Table 13).

The differences in treatment outcomes among WHO regions were similar to those reported in previous years. Documented treatment success rates by DOTS programmes varied from 74% in Europe and Africa, to 87% in South-East Asia and 91% in the Western Pacific, the latter two regions having exceeded the 85% target (Table 12, Figure 18). Death during treatment was most common in the African Region (7%), where a higher fraction of cases are HIV-positive, and in the European Region (7%), where a higher fraction of cases are drug resistant (eastern Europe) or occur among the elderly (western and central Europe). Treatment interruption (default) was most frequent in the African Region (9%) and the Eastern Mediterranean Region (8%). Transfer without follow-up was also especially high in the African Region (5%). Treatment failure was conspicuously high in the European Region (7%), mainly because failure rates were high in eastern Europe.

DOTS treatment success reached or exceeded 85% in eight HBCs (Table 12), and in 57 countries in total. It was under 60% in Zimbabwe and the Russian Federation, and 90% or more in Cambodia, China, and Viet Nam. Treatment results for individual African countries once again point to the effects of HIV and inadequate patient support: cohort death rates were more than 7% in Mozambique, South Africa, UR Tanzania and Zimbabwe. HIV may also have contributed to the high death rate in Thailand (7%) although, among Asian countries, Thailand has a relatively high proportion of elderly patients ( Annex 1).

Treatment outcomes are also poor in some African countries because many patients are lost to follow-up: more than 10% of patients had no recorded outcome in Ethiopia, Kenya, Nigeria, South Africa, Uganda and Zimbabwe (Table 12). The same was true of Brazil, Pakistan, the Philippines and the Russian Federation. Large numbers of patients completed treatment without confirming cure (a final, negative sputum smear) in Brazil (35%) and Uganda (39%).

A total of 496 569 patients were reported to have been re-treated under DOTS in 2004 (Table 14). While some patients remained on treatment (included with those not evaluated), the re-treatment success rate by the end of 2005 was 73%.

When the three registration categories (re-treatment after relapse (post cure), failure and default) are distinguished and compared with new TB patients, three patterns appear. First, the treatment success was lower on average for re-treatment (73%) than for new cases (84%) (Tables 12, 14). In the 2004 cohort of re-treated patients, re-treatment success was higher post-relapse than post-default in eight out of eight HBCs that provided data, and higher post-default than post-failure in four out of seven HBCs (Annex 2). Second, patients who defaulted from their first course of treatment tended to default when treated again. In all eight HBCs that submitted data, patients who were re-treated after default did not complete the subsequent course of treatment more often than patients who were re-treated after relapse or failure. Third, the regional distribution of adverse re-treatment outcomes resembled the pattern observed for new cases. For example, countries in the African Region reported high death rates (11%; Table 14). Countries in the European Region reported high rates of death (10%) and treatment failure (11%). Re-treatment success was much lower than 85% in all regions except the Western Pacific.

For non-DOTS areas, only five of the 12 HBCs that do not have full DOTS coverage provided treatment results for new smear-positive patients in the 2004 cohort. In India, 93% of 23 677 patients were not evaluated. In China, 91% of 7437 patients were treated successfully. Brazil, the Russian Federation and South Africa reported treatment success rates of 70% (of 20 349 patients), 61% (of 18 570) and 55% (of 5921), respectively.

Meeting targets for case detection and cure – results by country, region and worldwide

The data and estimates in this report suggest that the world as a whole narrowly failed to meet the targets for case detection (60%/70%) and treatment success (84%/85%). Both targets were reached in the Western Pacific Region, and the South-East Asia Region achieved more than 85% treatment success. All other WHO regions missed both targets. The European Region performed worst on both indicators.

Data on both treatment success and case detection were provided by 187 DOTS countries. Case detection exceeded 50%, and treatment success exceeded 70%, in 85 countries (Figure 18). Of these countries, 26 appear to have reached both WHO targets. They include the HBCs China, the Philippines and Viet Nam (Figures 19, 20). Of 164 countries that provided data for both the 2003 and the 2004 cohorts, 87 (53%) showed higher treatment success rates for the 2004 cohort, and 59 of 177 (33%) improved case detection by more than 5% between 2004 and 2005.

The country profiles in Annex 1 give more details of progress in each of the 22 HBCs. Annex 2 tabulates case detection and treatment success rates by country over the 11 years for which data are available.

Progress towards the Millennium Development Goals

Trends in incidence, prevalence and mortality

With the 8.8 million new incident TB cases in 2005, there were 14.1 million prevalent cases (218/100 000) on average (Table 9). An estimated 1.6 million people (24/100 000) died from TB in 2005, including those coinfected with HIV (195 000). The sequence of annual estimates suggests that all three major indicators – incidence, prevalence and mortality rates – are now falling globally. Prevalence was already in decline by 1990, mortality peaked before the year 2000, and incidence has begun to fall since 2003 (Figure 21). TB prevalence continued to fall globally between 1990 and 2015 because, in Africa, HIV caused a smaller increase in prevalence than in incidence or mortality. In addition, in Asia, our calculations suggest that DOTS has reduced prevalence more than incidence or mortality.

The fall in the global incidence rate, if confirmed by further monitoring, satisfies MDG 6, target 8. The targets set by the Stop TB Partnership – to halve prevalence and death rates by 2015 (compared with levels in 1990) – are more demanding but have, perhaps, almost been reached in the Region of the Americas (Figure 22).1 Prevalence and death rates have fallen in South-East Asia and the Western Pacific Region at rates that will, if maintained, reach the targets by 2015. Estimates for the Region of the Americas suggest that prevalence and death rates in 2005 had already fallen to approximately half their 1990 values. In the Eastern Mediterranean Region, both indicators are falling, but too slowly to meet the 2015 targets.

In line with the trends in incidence (Figure 7), prevalence and death rates increased in the African and European regions between 1990 and 2005, but most dramatically in the former. Estimates for these two regions in 2005 are very much larger than the 2015 target values. The combined data from all regions suggest that the world as a whole will not meet the 2015 targets at the current rate of progress.

Epidemic trends and the age distribution of TB cases

The specific effects on TB epidemiology of HIV infection, drug resistance, the impact of DOTS and other phenomena cannot easily be disentangled in routinely collected data. One of several reasons is that the time series of case notifications do not always reflect underlying trends in incidence. The true incidence and its trend may be obscured by the variable effort given to case-finding, by changing diagnostic procedures and by fluctuations in the consistency of reporting. However, the age distribution of notified cases is less susceptible to the vagaries of reporting, and trends in the age of TB cases are more likely to reflect underlying epidemiological processes.

Case reports from Viet Nam show no decline in the overall notification rate, even though the NTP has met the WHO targets for case detection and cure for more than a decade (Annex 2). Figure 23a reveals that, while the average age of older men and women with TB (≥55 years) has been rising, as expected when transmission is in decline, the average age of TB patients aged 15–54 years has been falling (left). The same is true in Myanmar (Figure 23b), and in Bangladesh, Sri Lanka and Thailand (not shown). Data from China show that new TB patients aged 55 years and over are getting older on average each year, but this is not true for younger patients (Figure 23c). In Viet Nam, the changes have been faster for women than men, opening up an age gap between male and female patients that already existed during the 1990s in Myanmar, and which has persisted until 2005.

The spread of HIV infection is one possible reason for the shift towards younger adults in these Asian countries. Another is that transmission is continuing among younger adults but not among the elderly. In Viet Nam, the shift is due to an increase in case notification rates among 15–24 years-olds (especially men), coupled with a fall in notifications among people aged 25–54 years (especially women). In Indonesia, the average age of men and women with TB has been falling in both younger and older age classes (Figure 23d). This suggests an explanation other than HIV, at least for people aged 55 years and over. In Morocco, the average age of men with TB aged 15–54 years is increasing, while for women it is decreasing (Figure 23e).

The average age of TB patients is also falling among people aged 15–54 years in the United States of America (Figure 23f). The most likely explanation is the growing proportion of cases among immigrants, although it may be reinforced by the age shift in some high-burden countries. During the period 2001–2005, Viet Nam (Figure 23a) was ranked third (behind Mexico and the Philippines) as a source of TB patients born outside the USA.2

In UR Tanzania and Uganda (Figures 23g, 23h), by contrast, the average TB patient is getting older in both age classes. This finding for younger men and women is consistent with, but not proof of, the view that the HIV epidemics are in decline in these countries3 and that, as a consequence, TB incidence was stable or falling by 2005.

Footnotes

1 See also: Health situation in the Americas - basic indicators. Washington D.C., Pan American Health Organization, 2006 (PAHO/HDM/HA/06.01).

2 Reported tuberculosis in the United States, 2005. Atlanta GA, Centers for Disease Control and Prevention, 2005.

3 AIDS epidemic update: December 2006. Geneva, UNAIDS/WHO, 2006.

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