Results
Progress towards the Millennium Development Goals
Countries reporting to WHO
By the end of 2004, 199 (94%) of 211 countries and territories reported case notifications for 2003 and/or treatment outcomes for patients registered in 2002. These countries include 99% of the world’s population. WHO received reports from all 22 HBCs.
Case notifications and incidence
The 199 countries reporting to WHO in 2003 notified 4.4 million new and relapse cases, of which 1.9 million (44%) were new sputum smear-positive (Table 3; Figure 1). Among these notifications, 3.7 million were from DOTS areas, including 1.8 million smear-positives. A total of 17.1 million cases, and 8.6 million smear-positives, were notified by DOTS programmes between 1995 and 2003. Based on surveillance and survey data, we estimate that there were 8.8 million new cases of TB in 2003 (140 per 100 000), including 3.9 million (62 per 100 000) smear-positive cases (Table 4; Figure 2).
The African Region (24%), South-East Asia Region (35%), and Western Pacific Region (22%) together accounted for 82% of all notified cases and similar proportions of new smear-positive cases. Because DOTS emphasizes diagnosis by sputum smear microscopy, 47% of all new and relapse cases were smear-positive (45–60% expected) in DOTS areas, compared with 29% elsewhere. Similarly, 58% of new pulmonary cases were smear-positive under DOTS (55–70% expected), compared with 35% elsewhere (Table 3).
The ranking of countries by number of incident TB cases has drawn attention to the 22 HBCs, but the magnitude of the TB burden in individual countries is better expressed as the incidence rate per capita. Among the 15 countries with the highest estimated TB incidence rates per capita, 12 are in Africa (Figure 3).
Case notifications from African countries show other patterns that are likely to be associated with HIV infection. First, women aged 15–24 years make up a higher proportion of TB cases in countries with higher rates of HIV infection (Figure 4a). This is consistent with the observation that HIV prevalence tends to be higher in women than men in this age range, and the difference between the sexes is bigger where HIV infection rates are higher. Second, the average age of smear-positive TB cases is typically lower where HIV infection rates are higher, especially for women (Figure 4b). This is another sign that younger rather than older women are more likely to be infected with HIV. Third, the proportion of smear-negative cases among all pulmonary TB cases tends to be higher in African countries with higher rates of HIV infection (data not shown). However, this last association is weak (R2 = 0.16, P = 0.02) and could be confounded by the quality of diagnosis if, for example, smear microscopy has become less reliable where the number of HIV-infected TB patients has increased substantially.
Some patterns in the case notification data are striking, but not easy to explain. For example, the number of extrapulmonary TB cases as a proportion of the total reported is consistently different among WHO regions. Between 1995 and 2003, the proportion was lowest in the Western Pacific Region (mostly <5%) and highest in the Eastern Mediterranean Region (20–30%; see Figure 5). We do not know whether these are real epidemiological differences, or due to regional diagnostic biases. Surprisingly, the proportion of cases diagnosed as extrapulmonary disease has not increased in the African Region, despite the growing impact of HIV on the TB epidemic. This raises the question of whether NTPs in Africa are missing extrapulmonary cases.
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 distinct regions of the world (Figure 6). In six of these regions, the trend in the incidence rate has been downward.
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 HIV infection, incidence has been pushed upwards by the spread of HIV, but the rate of increase has fallen from a maximum exceeding 15% per year in the early 1990s (Figure 6). In African countries with lower rates of HIV infection, the rate of increase in TB has never been as high (2–3% per year), but neither are there signs that the increase is slowing. In eastern Europe, the rate of increase reached nearly 15% annually by 1995, but the increase now appears to have been halted, and incidence is once again in decline.
The global trend is obtained by summing the estimated numbers of TB cases across all nine regions (Figure 7). Worldwide, the incidence rate of TB was growing at a maximum of around 1.5% per year in 1995, but less than 1% per year by 2003.
TB and HIV
Some countries have carried out surveys of the prevalence of HIV in TB patients, either nationally or locally, and the results have been reported via the data collection form or the supplementary TB/HIV questionnaire. Although the accuracy of the data is not known because, for example, the design of the surveys has not been fully described, a growing number of countries are testing TB patients for HIV infection.
The prevalence of HIV infection in TB patients can be derived from the incidence rate ratio (IRR). IRR is estimated from the relationship between HIV prevalence in adult TB patients and HIV prevalence in the adult population, where both have been measured together (Figure 8). The IRR derived from the national surveys in this set of data is 8.3 (95% CI, 6.1–10.8), which is higher than, but not significantly different from, the previously published estimate of 6.0 (3.1–8.0). 24
Further HIV surveys among TB patients will give, once the data have been validated, better direct measures of the TB/HIV association for the countries surveyed and, through the IRR, better indirect estimates for countries that do not yet test TB patients for HIV infection, thereby improving the distribution map in Figure 9.
DOTS coverage
The total number of countries implementing DOTS increased by two during 2003, bringing the total to 182 out of 211 (Figure 10). All 22 HBCs have had DOTS programmes since 2000; many of these programmes have been established for much longer.
DOTS coverage within countries has steadily increased since 1995 (Figure 11; Table 5). By the end of 2003, 77% 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 70% in all regions except Europe (Figure 12).
Case detection
The 4.4 million cases of TB (new and relapse) notified in 2003 represent half (50%) of the 8.8 million estimated new cases; the 1.9 million new smear-positive cases notified also account for half (50%) of the 3.9 million estimated (Table 3, Table 4). In parallel with trends in case notifications, the detection rate of all TB cases, from DOTS and non-DOTS programmes, has remained stable since 1995, while the detection rate of smear-positive cases has slowly increased (Figure 13). Therefore, the proportion of all cases diagnosed as smear-positive has been rising.
DOTS programmes detected an estimated 43% of all new and relapse cases, and 45% of new smear-positive cases, in 2003. The detection rate achieved by DOTS programmes has been rising more quickly than the overall case detection rate, and has accelerated since 2000. The 7.5% increase in DOTS case detection between 2002 and 2003, an additional 324 000 smear-positive cases, is the largest annual increase so far reported. If this rate of increase is maintained, the estimated detection rate will be 60% in 2005. To reach the 70% target by 2005, DOTS programmes must find and treat an extra 488 000 cases in each of the two remaining years.
Because case detection under DOTS has increased faster than the overall rate of case detection, the proportion of notified smear-positive cases that were notified by DOTS programmes has also increased, reaching 90% in 2003. DOTS programmes have continued to recruit largely from the pool of patients that would have been detected anyway in the public sector.
Although more cases are recruited to DOTS programmes each year, the case detection rate within DOTS areas (measured by the ratio of case detection to population coverage) has changed little, averaging 52% worldwide between 1996 and 2003 (Figure 14). There are signs of a slow rise in the HBCs, from 35% in 1995 to 56% in 2003, due mostly to improvements in Bangladesh, India, Indonesia, Myanmar and the Philippines.
Smear-positive case detection rates by DOTS programmes in 2003 were lowest in the European Region (23%) and highest in the African Region, Region of the Americas and Western Pacific Region (all 50%; see Figure 15, Table 6). The rate of improvement in case detection by DOTS programmes has been roughly the same in all WHO regions except the South-East Asia Region, where the acceleration in case-finding has been visible since 1998, driven mainly by DOTS expansion in India.
In the Region of the Americas, European Region and South-East Asia Region, significant numbers of smear-positive cases were reported, as usual, from outside DOTS programmes (Figure 16a). In the Region of the Americas, the estimated proportion of smear-positive cases detected from all sources exceeded 70%. 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. There were similar differences among regions in the detection rates of all TB cases (Figure 16b).
Of the additional smear-positive cases reported by DOTS programmes in 2003 (compared with 2002), 63% were in India (39%) and China (24%; Figure 17). Although China and India have made big improvements in case detection, these two countries still account for an estimated 36% of all undetected smear-positive cases (Figure 18). They are among eight countries that together account for two thirds (67%) of all undetected cases in 2003. In order of importance, these are: India, China, Indonesia, Nigeria, Bangladesh, Pakistan, Ethiopia and the Russian Federation.
Outcomes of treatment
More than 1.4 million new sputum smear-positive cases were registered for treatment in DOTS programmes in 2002, approximately the same number that were notified that year (Table 7, Annex 2). 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 and the Philippines (where about 10% of notified cases were not registered for treatment) and Afghanistan (where 20% of cases registered for treatment were not notified).
The cure rate among all cases registered under DOTS was 73%, and a further 9% completed treatment (no laboratory confirmation of cure), giving a reported, overall treatment success rate of 82%. An estimated 30% of all smear-positive cases arising in 2002 were treated successfully by DOTS programmes. In non-DOTS areas, the quality of reporting was worse: only four HBCs provided data for the 2002 cohort (Table 8).
By WHO region, the documented treatment success rates by DOTS programmes varied from 73% in the African Region to 85% in the South-East Asia Region and 91% in the Western Pacific Region, the latter two regions having met the 85% target (Table 7, Figure 19). 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 Europe). Treatment interruption (default) was most frequent in the African Region (11%) and the Eastern Mediterranean Region (8%). Transfer without follow-up was also especially high in the African Region (7%). Treatment failure was conspicuously high in the European Region (6%), mainly because a high proportion of patients in eastern Europe are recorded as failures.
DOTS treatment success exceeded 85% in seven HBCs (Table 7). It was under 70% in 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 9% or more in Mozambique, South Africa, the United Republic of Tanzania and Zimbabwe. But programme performance also remains poor in some African countries. For example, more than 15% of patients were lost to follow-up in Ethiopia, Kenya, South Africa, Uganda and Zimbabwe. Large proportions of patients completed treatment without confirming cure (a final, negative sputum smear) in Ethiopia (17%) and Uganda (31%). Uganda reported the lowest proportion of successful treatments among the 22 HBCs (60%). The aggregated treatment results for the European Region are strongly influenced by the performance in the Russian Federation, where 13% of patients died, 9% failed treatment and 11% were lost to follow-up.
A comparison of treatment results for nine consecutive cohorts (1994–2002) shows that the overall success rates have been 80% or more in DOTS areas since 1998 (Table 9). Treatment success rates have been persistently poor outside DOTS programmes in all regions, principally because large fractions of cases are not registered or evaluated.
In DOTS areas, about 250 000 cases were registered for re-treatment in 2002 (Table 10; Annex 2). Some patients remain on treatment (included with those “not evaluated”), but the latest data give an overall treatment success rate of 72%. When the three registration types (re-treatment after relapse, failure and default) are distinguished and compared with new TB patients, three patterns emerge. First, the comparative success of re-treatment was consistent with expectations: lower on average for re-treatment (72%) than for new cases (82%), but higher for relapses (71%), intermediate for defaulters (68%) and lowest for failures (58%). The rank order relapse > default > failed held for six out of eight HBCs that provided data, and for five out of six WHO regions. Second, patients who defaulted from their first course of treatment tended to default when treated again (17% of patients that were re-treated after default failed to complete the subsequent course of treatment, compared with 11% among all re-treated patients and 7% of patients on their first course of treatment). This was true in all six WHO regions. Third, the regional distribution of adverse re-treatment outcomes resembled the pattern observed for new cases. Thus, countries in the African Region reported high death rates (10%), and many patients were lost to follow-up (28%). Countries in the European Region reported high rates of death (10%) and treatment failure (12%).
Trends in case detection and treatment success: overview of national DOTS programmes
Data on both treatment success and case detection were provided by 177 DOTS countries. Case detection exceeded 50%, and treatment success exceeded 70%, in 75 countries (Figure 20). They include the HBCs Cambodia, the Democratic Republic of the Congo, Myanmar, the Philippines, Thailand and Viet Nam. Of these countries, 22 appear to have reached the WHO targets, but together the 75 countries accounted for only 17% of all new smear-positive cases in 2003. Viet Nam was still the only member of the current group of HBCs to have reached targets for both case detection (>70%) and treatment success (>85%), although Myanmar and the Philippines are close to these targets (Figure 21). Three HBCs – Brazil, the Russian Federation and Uganda – had low rates of both case detection (<50%) and treatment success (<70%). More details of progress in each of the 22 HBCs can be found in the profiles (Annex 1).
Of 161 countries that provided data for both the 2001 and 2002 cohorts, 91 (57%) showed higher treatment success rates for the 2002 cohort, and 68 of 172 (40%) improved case detection by more than 5%. Annex 2 tabulates case detection and treatment success rates by country over the nine years for which there are data.
Trends in prevalence and death rates
The trends in prevalence and mortality for each region are calculated from the trend in incidence (Figure 6) and from estimates of the duration of illness (e.g. time smear-positive) and the case-fatality rate. Summing estimates from across the regions gives the global trends in prevalence and deaths, which are shown in Figure 22a with and without the contribution of HIV-positive TB patients, and in comparison with the trends in incidence (Figure 7). Although the global incidence rate was still increasing in 2003, prevalence and death rates had already begun to fall. Excluding HIV-positive TB patients, the incidence rate increased 0.6% between 2002 and 2003, prevalence fell by 5.7% and mortality by 3.5%. When TB patients coinfected with HIV are included, the incidence rate increased by 1.0%, and prevalence and mortality fell by 5.5% and 2.5%, respectively. The differential effects of HIV on incidence, prevalence and mortality are also visible, and magnified, in the trends for countries of eastern and southern Africa, where all three indicators were still increasing in 2003 (Figure 22b). Among the nine regions defined in Figure 6, TB prevalence and death rates increased between 2002 and 2003 only in the two African regions; as for incidence rates, prevalence and deaths were falling or stable in the other seven regions.
Footnote
24 Corbett EL et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Archives of Internal Medicine, 2003, 163:1009–1021.