Tuberculosis (TB)

Results

Monitoring progress in TB control

Countries reporting to WHO

By the end of 2004, 200 (95%) of 211 countries and territories reported case notifications for 2004 and/or treatment outcomes for patients registered in 2003 (Annex 2). These countries include 99.9% of the world’s population. Reports were submitted by all 22 HBCs.

Case notifications and incidence estimates

The 200 countries reporting to WHO in 2004 notified 4.9 million new and relapse cases, of which 2.2 million (46%) were new smear-positive (Table 5; Figure 1). Among these notifications, 4.4 million were from DOTS areas, including 2.1 million new smear-positives. A total of 21.5 million new and relapse cases, and 10.7 million new smear-positives, were notified by DOTS programmes between 1995 and 2004. Based on surveillance and survey data, we estimate that there were 8.9 million new cases of TB in 2004 (140 per 100 000), including 3.9 million (62 per 100 000) new smear-positive cases (Table 6; Figures 2, 3).

Comparing different parts of the world, the African Region (24%), South-East Asia Region (35%) and Western Pacific Region ( 24%) together accounted for 83% of all notified new and relapse cases and similar proportions of new smear-positive cases in 2004. Since DOTS emphasizes diagnosis by sputum smear microscopy, 47% of all new and relapse cases were new smear-positive (45–60% expected) in DOTS areas, compared with 30% elsewhere. Among new pulmonary cases reported by DOTS programmes, 58% were new smear-positive (55–70% expected), compared with 40% elsewhere (Table 5).

The ranking of countries by number of incident TB cases has given prominence to the 22 HBCs, but the magnitude of the TB burden in individual countries can also be expressed as the incidence rate per capita. Among the 15 countries with the highest estimated TB incidence rates per capita, 11 are in Africa (Figure 4).

Using the 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 rate (all forms) for nine epidemiologically different regions of the world (which are subdivisions of the six WHO regions) for the period 1990 to 2004. In six of these regions, the incidence rate was stable or falling (Figure 5). As reported in 2005, incidence rates have been increasing for most of the period since 1990 in African countries with low and high rates of HIV infection, and in eastern Europe, although the patterns of change in the three regions are quite different. In African countries with high rates of HIV infection, incidence has been driven upwards by the spread of HIV, but the rate of increase has fallen from a maximum exceeding 14% per year in the early 1990s to less than 3% per year by 2004 (Figure 5). In African countries with lower rates of HIV infection, TB incidence has increased more slowly (1–2% per year), but there are no signs that the increase is slowing. Where HIV infection rates are higher in adult populations, they are also estimated to be higher among new TB patients. Figure 6 maps the distribution of HIV among TB patients, showing the relatively high rates in countries of eastern and southern Africa.

In eastern Europe, the rate of increase reached nearly 14% annually by 1995, but the increase appears to have halted around year 2000, and incidence is once again in decline. The resurgence of TB in eastern Europe during the 1990s has been associated with (but primarily not caused by) relatively high rates of MDR-TB among new and previously treated patients.

Worldwide, the incidence rate of TB was growing at a maximum of 1.2% per year in 1997, but at 0.6% per year by 2004 (Figure 5).

DOTS coverage

The total number of countries implementing DOTS increased steadily since 1995 and is approaching a limit at 183 in 2004 (Figure 7). 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 8; Table 7). By the end of 2004, 83% of the world’s population lived in counties, districts, oblasts and provinces of countries that had adopted DOTS. Coverage was reported to be more than 80% in all regions except Europe (Figure 9).

Case detection

The 4.9 million new and relapse cases of TB notified in 2004 represent 54% of the 8.9 million estimated new cases; the 2.2 million new smear-positive cases notified account for 56% of the 3.9 million estimated (Tables 5, 6). The detection rate of all TB cases, from DOTS and non-DOTS programmes, remained approximately stable from 1995 to 2001, but increased between 2002 and 2004 (Figure 10b). The detection rate of new smear-positive cases from all sources slowly increased from 1995 to 2001, and then more quickly from 2002 to 2004 (Figure 10a). The increase from 2002 to 2004 is attributable mostly to increases in the numbers of new smear-positive cases reported in the South-East Asia and Western Pacific regions.

DOTS programmes detected an estimated 50% of all new and relapse cases and 53% of new smear-positive cases in 2004. The detection rate achieved by DOTS programmes, of both smear-positive and all TB cases, has accelerated sharply since 2000, rising more quickly than the overall (DOTS and non-DOTS) case detection rate (Figure 10). The key observation in relation to the WHA target is that DOTS case detection increased from 45% in 2003 to 53% in 2004 – an additional 350 000 new smear-positive cases – the largest annual increase so far reported. In order to reach the target of 70% by the end of 2005, DOTS programmes must find 2 805 000 new smear-positive cases during 2005; that is, 716 000 more than the 2004 total.

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 94% in 2004. Thus, almost all (91%) TB cases reported to WHO in 2004 were reported by DOTS programmes.

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 64% by 2004 (Figure 11). Similarly, the detection rate within DOTS areas in the HBCs was roughly stable from 1997 to 2001 (average 48%), but increased to 62% in 2004, mostly because of improvements in Bangladesh, Brazil, China, India, Indonesia, Myanmar and the Philippines (Figure 11).

Returning to national detection rates, and comparing the WHO regions, new smear-positive case detection rates by DOTS programmes in 2004 were lowest in the European (26%) and Eastern Mediterranean regions (33%) and highest in the Region of the Americas (59%) and the Western Pacific Region (65%; Figure 12, Table 8).

The rate of improvement in case detection by DOTS programmes has been roughly the same in the African Region, the Eastern Mediterranean Region and the European Region. None of these three regions is on course to reach the 70% target by the end of 2005.

Case-finding in the South-East Asia Region has been accelerating since 1998, mainly as a result of the rapid implementation of DOTS in India, supported by improvements more recently in Bangladesh, Indonesia and Myanmar. There were marked increases in case detection in the Region of the Americas and the Western Pacific Region between 2003 and 2004 attributable mostly to improvements, respectively, in Brazil and China. If the rate of improvement in case-finding is maintained in these three regions, all will reach the 70% target by the end of 2005.

In the Region of the Americas and the European Region, significant numbers of smear-positive cases were reported, as usual, from outside DOTS programmes. In the Region of the Americas, and especially in Brazil, the estimated proportion of smear-positive cases detected from all sources exceeded 70% (Table 8, Figure 13a). Thus, the target for case detection would have been reached in this region if all patients in whom TB had been diagnosed had been treated under DOTS. The Region of the Americas and the European Region also reported significant numbers of new and relapse TB cases from outside DOTS programmes, and the total detected exceeded 70% in the European Region (Figure 13b).

Of the additional new smear-positive cases reported by DOTS programmes in 2004 (compared with 2003), 34% were in China and 30% were in India (Figure 14). Although China and India have made big improvements in case detection, these two countries still account for an estimated 31% of all undetected new smear-positive cases. They are among eight countries that together account for 61% of all cases that were not detected under DOTS in 2004 (Figure 15).

Comparison of methods for evaluating case detection

To estimate the proportion of culture-positive patients that are also smear-positive, we want, ideally, to compare smears and cultures for every patient, knowing whether each test for each patient was positive or negative. In fact, TB was diagnosed in some patients by smear but not culture, or vice versa, and the missing data could generate biased estimates. Figure 16 shows the ratio of smear-positive to culture-positive TB patients, reported from all sources in 25 countries of the European Region in 2004, where the proportion of patients that were classified by both smear and culture was (a) more than 75% (n = 6), (b) 50% to 75% (n = 13), or (c) less than 50% (n = 6). Because the data in group (a) are most reliable, and because the ratios calculated for countries in groups (b) and (c) mostly do not differ significantly from those in (a),1 we have used the ratio estimated from countries in group (a), which is 0.59 (95% CL +/- 0.04).

This calibration ratio allows us to estimate culture-positive incidence rates (formula 7) and culture-positive case detection rates for each country, so that the latter can be compared with the smear-positive case detection rates. In the European Region, the case detection rates based on culture alone were seldom better than those based on smears, and commonly much worse. Each point in Figure 17a represents a different country, and most points lie under the line of equality. Some countries reported no culture-positive TB cases (points on horizontal axis). By contrast, the case detection rates for all laboratory-confirmed cases were not systematically different from those calculated from smears (Figure 17b).

The diagnosis of all forms of TB by all methods (smear, culture, radiography, clinical examination), when compared with diagnosis by smear, shows a different pattern. The case detection rates for all TB patients in European countries are almost always higher than the detection rates based on smears (filled circles representing European countries lie above the line of equality in Figure 17c). This pattern is unique to the European Region, and different from countries in the Region of the Americas, for which points lie mostly below the line of equality in Figure 17c. Figure 17c shows, for the countries of the Americas and Europe, a difference that is also visible in the aggregated data in Figures 13a and 13b. For the other four WHO regions, there is no systematic difference between the detection rates of smear-positive and all forms of TB cases (Figure 17d).

Outcomes of treatment

More than 1.7 million new smear-positive cases were registered for treatment in DOTS programmes in 2003, approximately the same number that were notified that year (Table 9). Discrepancies between the numbers of cases notified and registered for treatment were small globally, by region and for most HBCs, the largest differences being in Kenya, the,Philippines and South Africa (Table 9).

The cure rate among all cases registered under DOTS was 75%, and a further 7% completed treatment (no laboratory confirmation of cure), giving a reported, overall treatment success rate of 82%. An estimated 36% of all smear-positive cases arising in 2003 were treated successfully by DOTS programmes. For non-DOTS areas, only 4 of the 13 HBCs that do not have full DOTS coverage provided data for the 2003 cohort (Table 11).

Comparing WHO regions, the documented treatment success rates by DOTS programmes varied from 72% in the African Region to 85% in the South-East Asia Region and 92% in the Western Pacific Region, the latter two regions having apparently met the 85% target (Table 9, Figure 18). Fatal outcomes were most common in the African Region (7%), where a higher fraction of cases are HIV-positive, and in the European Region (6%), 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 (10%) and the Eastern Mediterranean Region (9%). 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 exceeded 85% in eight HBCs (Table 9). It was under 70% in Nigeria, the Russian Federation, South Africa, Uganda and Zimbabwe. Treatment results for individual African countries once again point to the effects of HIV: cohort death rates were more than 7% in Mozambique, South Africa, the United Republic of Tanzania and Zimbabwe. HIV may also have contributed to the high death rate in Thailand (10%) although, among Asian countries, Thailand has a relatively high proportion of elderly patients (Annex 1).

Treatment outcomes are persistently poor in some African countries. For example, 15% or more patients were lost to follow-up in Ethiopia, Kenya, Nigeria, South Africa, Uganda and Zimbabwe. Large proportions of patients completed treatment without confirming cure (a final, negative sputum smear) in Ethiopia (16%), Uganda and Brazil (36%). The aggregated treatment results for the European Region are strongly influenced by the performance in the Russian Federation, where 10% of patients died, 12% failed treatment and 16% were lost to follow-up. These relatively poor results are undoubtedly linked to the high prevalence of MDR-TB.

A comparison of treatment results for 10 consecutive cohorts (1994–2003) of new smear-positive patients shows 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 1.7 million in 2003 (Tables 9, 10). Globally, treatment success rates since 1998 have been close to, but persistently below, the 85% target. The rates are mostly low outside DOTS programmes; the explanation, as in previous years, is that large fractions of registered cases are not evaluated, especially in South-East Asia (Figure 11). Furthermore, a smaller proportion of notified cases were registered for treatment (65% globally for non-DOTS compared with 98% for DOTS).

About 323 000 re-treated patients were monitored under DOTS in 2003 (Table 12). Some patients remain on treatment (included with those not evaluated), but the latest data give an overall treatment success rate of 73%. When the three registration categories (re-treatment after relapse (post cure), failure and default) are distinguished and compared with new TB patients, we see three patterns that have been noted in previous WHO reports. First, the treatment success was lower on average for re-treatment (73%) than for new cases (82%). In the 2002 cohort of re-treated patients, we found that success was highest for those re-treated after relapse, intermediate for previous defaulters and lowest for previous failures. Similarly, in the 2003 cohort, re-treatment success was higher post-relapse than post-default in 8 out of 9 HBCs that provided data, and higher post-default than post-failure in 5 out of 8 HBCs (Annex 2).

Second, patients who defaulted from their first course of treatment tended to default when treated again. In all 9 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 12). Countries in the European Region reported high death rates (11%) and treatment failure (16%). Re-treatment success was much lower than 85% in all regions except the Western Pacific.

Trends in case detection and treatment success: overview of national DOTS programmes

Data on both treatment success and case detection were provided by 172 DOTS countries. Case detection exceeded 50%, and treatment success exceeded 70%, in 82 countries (Figure 19). They include the HBCs Cambodia, China, Democratic Republic of the Congo, India, Indonesia, Myanmar, the Philippines, Thailand and Viet Nam. Of these countries, 26 appear to have reached the WHO targets, but together they accounted for only 9% of all new smear-positive cases reported in 2003. Among the HBCs, Viet Nam has exceeded both targets since 1997. Based on the cohort data for 2003 (treatment success 88%) and case notifications for 2004, the Philippines is the second HBC to have reached both targets (Figure 20). Cambodia, China and Myanmar are approaching these targets. Two HBCs (Uganda and Zimbabwe) had low rates of both case detection (<50%) and treatment success (<70%). Of 166 countries that provided data for both the 2002 and the 2003 cohorts, 93 (56%) showed higher treatment success rates for the 2003 cohort, and 62 of 176 (35%) improved case detection by more than 5%.

Annex 1 has more details of progress in each of the 22 HBCs. Annex 2 tabulates case detection and treatment success rates by country over the 10 years for which data are available.

Trends in prevalence and death rates

In 2004, there were 14.6 million prevalent cases (229/100 000), of which 6.1 million were smear-positive (95/100 000). An estimated 1.7 million people (27/100 000) died from TB in 2004, including those coinfected with HIV (248 000).

Figure 21 compares estimates of the prevalence and deaths rates in 1990 (baseline year for the MDGs) and 2004, for each of the six WHO regions. Consistent with trends in incidence (Figure 5), prevalence and death rates have increased over this period in the African and European regions, but most dramatically in the former. Estimates for these two regions in 2004 are very much larger than the 2015 MDG target values (which are half the 1990 rates). Prevalence and death rates have fallen in the other four WHO regions, and the rate of decline between 1990 and 2004 suggests that the MDG targets can be reached in these regions of the world.


Footnotes

1 Outliers are Italy, Portugal, Romania, Slovakia and Switzerland. A full account of the methods underpinning this analysis is given in an unpublished technical note available from WHO: Estimating smear-positive and culture-positive case detection rates in Europe.

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