Tuberculosis (TB)

WHO report 2008
Global tuberculosis control

2.3 TB/HIV, MDR-TB and other challenges

2.3.1 Collaborative TB/HIV activities

Globally, there were an estimated 709 000 new HIV-positive TB cases in 2006 (see Chapter 1 for further details). This estimate accounts for the revisions to the global estimates of HIV prevalence in the general population that were published by UNAIDS in December 2007.1 The African Region accounts for 85% of estimated cases, India for 3.3%, the European Region for 1.8% and other countries for 9.4%.

Collaborative TB/HIV activities are essential to ensure that HIV-positive TB patients are identified and treated appropriately, and to prevent TB in HIV-positive people.2 These activities include establishing mechanisms for collaboration between TB and HIV programmes (coordinating bodies, joint TB/HIV planning, monitoring and evaluation, HIV surveillance); for HIV-positive people, intensified TB case-finding and, for those without active TB, IPT; infection control in health-care and congregate settings; HIV testing for TB patients; and, for those TB patients infected with HIV, co-trimoxazole preventive therapy (CPT) and ART.

Mechanisms for collaboration and policy development

Among 63 countries that have been identified as priorities at global level3 and which collectively account for 97% of estimated HIV-positive cases worldwide, around 40 had established coordinating bodies, developed a joint TB/HIV plan and were undertaking HIV surveillance by 2006 (Figure 2.4). Around 50 countries had policies for HIV counselling and testing among TB patients, as well as for provision of CPT and ART to those coinfected with HIV; these countries account for about 90% of the estimated number of HIV-positive TB cases globally. A relatively high number of countries also had policies for intensified case-finding among HIV-positive people. In contrast, a smaller number of countries had policies related to IPT (26 countries) and infection control (31 countries), with these countries accounting for only 66% and 41% respectively of the global number of HIV-positive TB cases. While there was variation in the extent to which mechanisms for collaboration or policies were in place in 2006, in all instances there was an improvement compared with 2005 (table 2.4).

When all countries that reported data are considered, the number of countries with policies is much higher, but the fraction of the global number of HIV-positive TB cases covered is almost the same (Table 2.5).

HIV testing for TB patients

HIV testing for TB patients is a critical entry point to interventions for both treatment and prevention. There was a substantial increase in provision of HIV testing for TB patients between 2002 and 2006, with reported numbers increasing from 21 806 patients across 9 countries in 2002 (less than 1% of notified TB cases) to 687 174 patients across 112 countries in 2006 – equivalent to 12% of notified TB cases (Figure 2.6). In the African Region, 287 945 patients (22% of all notified cases) were tested (Table 2.9).

This increase in numbers of patients tested for HIV may be exaggerated by the increase in the number of countries reporting data and the share of the global number of HIV-positive TB cases accounted for by reporting countries (see numbers and percentages below the bars of Figure 2.6). Stronger and clearer evidence that HIV testing has increased since 2004 is presented in Figure 2.7. This shows the number of TB patients who were tested for HIV in 64 countries that reported data for all three years 2004–2006. The number of TB patients tested for HIV in 11 African countries representing 57% of estimated HIV-positive TB cases globally (and 66% of cases in the African Region, data not shown) increased almost five-fold in three years, while the percentage of all notified cases that were tested increased from 7.5% to 35%. Most of this increase was driven by two countries (Kenya and South Africa) and, to a lesser extent, by Malawi and Zambia (data not shown). Outside the African Region, the number of patients tested for HIV also increased, but by a much smaller amount in absolute terms. The percentage of TB patients tested outside Africa was, however, relatively high (e.g. 56% in 2006).

Across all reporting countries (n=101), testing led to the detection of 186 217 HIV-positive TB patients. These detected cases represent approximately 26% of the number of HIV-positive TB cases estimated to exist in 2006 (Table 2.9). However, there is considerable variation among regions. In the South-East Asia and Western Pacific regions in particular, targeted HIV testing (of patients in specific geographical areas or of patients with specific risk factors) appears to result in a relatively high proportion of the estimated number of HIV-positive TB cases being identified through testing. In South-East Asia, only 4% of notified cases were tested, but this resulted in the detection of 40% of the region’s estimated HIV-positive TB cases. In the Western Pacific Region, the figures were 3% and 12%, respectively.

This progress in the number of TB patients being tested for HIV is impressive. However, there is room for further improvement, as illustrated by the high variability in current testing rates among countries (Figure 2.8). The high testing rates achieved by a few countries show that there is scope for increasing testing rates elsewhere.

Provision of CPT and ART to HIV-positive TB patients

A major reason for promoting HIV testing in TB patients is to facilitate provision of CPT and ART to HIV-positive patients. This seems to be working. The benefits of testing can be seen in the high proportion of TB patients testing positive for HIV who were treated with CPT (78%) and ART (41%) in 2006. These proportions represent a slight improvement from 2005 (Figure 2.9 and Figure 2.10). In absolute terms, the improvement in provision of CPT and ART is much more marked. In 2006, almost 146 586 HIV-positive TB patients were treated with CPT in 46 countries that collectively account for 75% of the global number of HIV-positive TB cases, and 66 601 were started on ART across 54 countries that account for 75% of the global number of HIV-positive TB cases. As with HIV testing, trends are somewhat distorted by the variation in the number of countries reporting data (see figures below bars in both Figure 2.9 and Figure 2.10). However, there has been a large increase in the number of patients benefiting from both treatment interventions since 2004. In Africa specifically, the proportion of patients in whom HIV infection was diagnosed who are started on CPT reached 78% in 2006; the figure for ART was 41% (Table 2.9).

Intensified TB case-finding and provision of IPT among HIV-positive people

Screening for TB among HIV-positive people attending HIV care services increased from 194 718 people in 2005 to 314 394 people in 2006 (Figure 2.11). Among those screened, 84 713 were found to have TB; this number is equivalent to 12% of the 709 000 HIV-positive TB cases estimated to exist globally. This high proportion suggests that if screening for TB was increased beyond its currently low levels (only 0.9% of the estimated 33 million HIV-positive people were screened in 2006), TB case-finding would improve.

Provision of IPT remains at very low levels, with reported numbers treated with IPT reaching only 27 056 in 2006 – equivalent to less than 0.1% of the estimated 33 million people estimated to be infected with HIV globally (Figure 2.11). The low number of people being treated with IPT is inconsistent with policy establishment: while 84 countries reported the existence of an IPT policy, only 25 reported any provision of IPT. Numbers on IPT are also dominated by Botswana, which accounted for 70% of the total number of people reported to be on IPT globally in 2006.

Progress against Global Plan targets

The Global Plan describes the progress required to implement collaborative TB/HIV activities for each year 2006–2015, within the framework of the goal of universal access to ART by 2010. The milestones or targets included for each year in the Global Plan provide a benchmark against which progress in practice can be assessed. A comparison of Global Plan expectations with implementation reported by countries is shown in Table 2.10. This shows that, among the 171 countries considered in the Global Plan, 541 415 TB patients were tested for HIV compared with 1.6 million specified in the Global Plan. The proportions of TB patients tested for HIV were 20% and 47% respectively. A total of 146 581 HIV-positive TB patients were started on CPT in 2006, compared with the 500 000 specified in the Global Plan. In terms of the percentage of TB cases found to be HIV-positive and that were enrolled on CPT, the comparison is much more favourable: 86% of TB cases in whom HIV infection was diagnosed were started on CPT in 2006 based on country reports, compared with the target of 46% for 2006 in the Global Plan. For ART, 66 542 diagnosed HIV-positive TB cases were reported to have been enrolled in 2006, compared with a target of 220 000 in the Global Plan. As for CPT, the figures are more impressive in terms of the percentage of diagnosed HIV-positive cases started on ART; 41% according to country reports compared with 44% in the Global Plan. The bigger differences between the absolute numbers of people receiving CPT and ART compared with similar numbers for the percentage of diagnosed HIV-positive TB cases started on such treatment in both country reports and the Global Plan are attributable to the shortfall in HIV testing. For patients to be treated with either CPT or ART, they must first be diagnosed with HIV, which means that a much higher percentage of TB patients must be tested for HIV.

For ART specifically among TB/HIV interventions, the WHO data collection form requests countries to provide projections of the number of HIV-positive patients who will be started on ART in 2007 and 2008, as well as actual provision of ART in 2006. These data are compared with the Global Plan targets for ART in Figure 2.12. About one third of the countries reported ART projections for 2007 and 2008. Nonetheless, among those countries that did report, anticipated progress is encouraging, with projected numbers higher than the Global Plan targets for those countries in 2007 and 2008.

Activity in HIV care services (intensified case-finding and IPT) is far from Global Plan targets (Table 2.10). The Global Plan target for 2006 was to screen 11 million HIV-positive people for TB; the actual figure reported was 314 211. IPT provision remains at very low levels, although, as noted above, Botswana is an exception.

Overall, implementation of TB/HIV interventions falls short of the Global Plan targets. Importantly, however, data from individual countries show that these targets are achievable if currently less well-performing countries emulate targets that have already been reached or exceeded in several countries.

2.3.2 Diagnosis and treatment of MDR-TB

The most recent estimates suggest that, globally, there were about 489 000 cases of MDR-TB in 2006. These cases are very unevenly spread, with 27 countries (of which 15 are in Eastern Europe) accounting for 86% of the total (Table 2.11). These 27 countries have been identified as priorities for improved diagnosis and management of MDR-TB at global level.

The Global Project on Anti-tuberculosis Drug Resistance Surveillance (DRS) continues to increase the number of countries from which a direct measure of the number of cases of MDR-TB is available. This allows estimates of the number of cases to be refined over time. By 2007, the project had collected data from 117 countries covering areas that contain more than 50% of global smear-positive TB cases. Recently, new data have become available from new areas of three HBCs (China, India, and the Russian Federation) and from three HBCs for the first time: Ethiopia, the Philippines and the United Republic of Tanzania. Furthermore, 33 countries reported information on resistance to second-line drugs among MDR-TB cases in surveys or through routine surveillance systems. Full details are available in the fourth global report on anti-TB drug resistance surveillance.4

Diagnostic services

Diagnosis of MDR-TB depends on the extent to which DST services are available and used (see also section 2.2.3 above on Case detection through quality-assured bacteriology). In 2006, 118 732 diagnostic drug susceptibility tests were reported among 108 countries, with 74% of these tests conducted in the European Region. The proportion of new cases for whom DST was done was also highest in the European Region (24%), followed by the Region of the Americas at 14% (Figure 2.13). The percentage of the regional number of MDR-TB cases accounted for by reporting countries was also relatively high in these regions, particularly for the European Region. In other regions, the proportion of new cases for whom DST was done was low among reporting countries. Figures were higher for all regions for re-treatment cases, ranging from 9% in the African Region to 24% in the European Region.

Among those tested in 2006, 23 353 cases of MDR-TB were diagnosed, of which just over half were in Europe. A total of 2 032 cases (8.7% diagnosed cases) were reported from GLC projects. Among the 27 global priority countries, 19 503 cases were notified, which is only 4.6% of the estimated number of cases in these countries (Table 2.11).

Scaling-up management of MDR-TB

The small number of MDR-TB cases diagnosed compared with the number of cases that are estimated to exist shows that an enormous amount of work remains to be done to improve the availability and provision of diagnosis and treatment for MDR-TB.

For the 27 global priority countries, the latest status of progress in introducing and scaling-up treatment of patients with MDR-TB in mid-2007 is shown in Table 2.12. Six countries have conducted a survey of drug resistance, implemented a GLC-approved pilot project, developed national guidelines for the management of MDR-TB and conducted related training, have scaled-up or are in the process of scaling-up activities, and have fully integrated MDR-TB treatment within the NTP including reporting of data: China, the Democratic Republic of the Congo, Estonia, Kazakhstan, the Republic of Moldova and Uzbekistan. Besides these countries, four others have reported expansion of activities: Azerbaijan, Kyrgyzstan, the Russian Federation and South Africa. Among all countries, the biggest expansion that is projected in absolute terms is in the Russian Federation, which forecasts that the number of MDR-TB cases treated will reach 24 000 in 2008, compared with just under 4 000 notified cases in 2006 (Table 2.11). Elsewhere, the increase in treated cases anticipated by NTPs that report being in the process of scaling-up is small in absolute terms. China is a notable example: while it ranks first globally in terms of estimated cases (130 548), the number of patients projected to be treated in 2008 is 388 (up from 165 cases in 2007), which is only 0.3% of the estimated cases (Table 2.11). At the other end of the spectrum, no activities related to the management of MDR-TB have begun in Nigeria or Pakistan, and, besides a survey of drug resistance, no further activities were reported by Ethiopia (Table 2.12).

Across all countries, increased implementation of MDR-TB treatment was reported by 39 countries. Consistent with this, projections of the number of cases that would be diagnosed and treated globally in 2007 (46 537 cases) were much higher than the 23 353 cases notified in 2006 (Table 2.14). Most of these cases are expected to be treated outside GLC projects, although the number enrolled for treatment in GLC projects is projected to increase more than five-fold by 2008, compared with 2005. Of all those cases notified in 2006 (within and outside GLC projects), it is not known what number were actually enrolled on treatment, and of those treated how many were treated according to WHO guidelines.5 All that can be said for certain is that the 2032 patients who were enrolled on treatment in GLC projects were being treated according to WHO guidelines.

Role of the Green Light Committee

Although many cases of MDR-TB are notified outside GLC projects, the GLC has put in place specific mechanisms to promote more rapid expansion of MDR-TB diagnosis and treatment. These include building partnerships with major funding mechanisms such as the Global Fund and UNITAID, reshaping and streamlining GLC application processes during 2006 and 2007, and facilitating the development of WHO guidelines for the programmatic management of drug-resistant TB in 2006.

By the end of 2007, 67 projects in 52 countries had been approved by the GLC, such that these projects will have access to high-quality and competitively-priced drugs for a cumulative total of over 30 000 patients with MDR-TB. In 2006 specifically, the GLC reviewed and approved applications for a total of 12 604 patients – six times more than in 2005. In 2006–2007, treatment programmes for MDR-TB in 20 countries were newly-approved by the GLC: these countries were Armenia, Bangladesh, Belize, Burkina Faso, Cambodia, China, the Democratic Republic of the Congo, Ecuador, Guatemala, Guinea, Kazakhstan, Lesotho, Mongolia, Paraguay, Rwanda, Samoa, Viet Nam, Uganda, Ukraine and Uruguay. At then end of 2007, most GLC-approved countries were in the Region of the Americas (14 countries) and the European Region (13 countries), followed by the African Region (7 countries), the Western Pacific Region (7 countries), the South-East Asia Region (6 countries) and the Eastern Mediterranean Region (5 countries).

These enhanced efforts by the GLC, however, cover less than 5% of patients with drug-resistant TB worldwide. There is an urgent need for countries to substantially increase the provision of treatment for patients with MDR-TB that meets the standards established in WHO guidelines.

Treatment outcomes

Given that it takes 18–24 months to treat patients with MDR-TB, the most recent year for which treatment outcome data were requested by WHO in 2007 was 2003. While 50 countries reported data, the size of the cohorts was too small (less than 40 in 42 countries; 28 of these countries had cohorts of fewer than 10 patients) to allow any useful analysis. The seven countries with larger cohorts are shown in Table 2.15. The best treatment success rate (70%) was in Latvia, which has a GLC-approved project. Treatment success rates were also relatively high in Brazil (60%) and Germany (63%), neither or which has a GLC-approved project. In contrast, outcomes were especially poor in two other countries without GLC projects: Lithuania and Romania (36% and 26% treatment success rates, respectively, and high death and treatment failure rates). To improve our understanding of treatment outcomes for patients with MDR-TB, more data from more countries, both GLC-approved and outside the GLC framework, are needed.

Progress against Global Plan targets

As with collaborative TB/HIV activities, the Global Plan sets out the progress required in provision of treatment for MDR-TB cases for each year 2006–2015. During 2007, the targets for the number of patients to be diagnosed and treated for MDR-TB were reviewed, and revised to make the targets for 2010 comparable to the goal of universal access to ART by 2010.6 The principal 2010 targets for MDR-TB are: (i) that diagnostic DST should be offered to all previously treated and chronic TB cases as well as to 90% of new TB cases with a high risk of having MDR-TB (e.g. contacts of MDR-TB cases, those for whom treatment is failing after 3 months); and (ii) that all those in whom MDR-TB is diagnosed should be enrolled in GLC-approved or equivalent treatment programmes. Despite the progress that has been made in some countries documented above, the number of MDR-TB patients notified in 2006 and country projections of the number of MDR-TB patients to be treated in 2007 and 2008 fall far behind the expectations of the Global Plan (Figure 2.14 and Table 2.16). In 2007, the Global Plan indicates that 52 000 MDR-TB patients should be diagnosed and treated, while reports from countries representing 80% of MDR-TB cases globally indicate a figure of 46 537. In 2008, the Global Plan indicates that 98 000 patients should be diagnosed and treated, while reports from countries representing 86% of MDR-TB cases globally indicate a figure of 46 227 (little different to 2007).

Differences between Global Plan expectations and country projections vary by region, as shown for 2007 in Figure 2.16. In the African Region, the Eastern Mediterranean Region and the Region of the Americas, country forecasts are higher than Global Plan expectations, with relatively large numbers of patients expected to be treated in Brazil and South Africa in particular (see also Chapter 3, where the high number of patients expected to be treated in South Africa is also reflected in budget data). However, in the three regions with the greatest number of MDR-TB cases (the European, South-East Asia and Western Pacific regions), meeting the expectations of the Global Plan will require substantial efforts to scale-up diagnosis and treatment, especially in China and India.

2.3.3 High-risk groups and special situations

Vulnerable populations such as prisoners, refugees and other high-risk groups are considered in NTP plans in 138 (68%) of 202 reporting countries. Among the 22 HBCs, 19 have included such populations in their plans, including prisoners (20 HBCs), refugees and displaced people (10 HBCs), slum dwellers (9 HBCs), cross-border populations (8 HBCs), migrant workers (5 HBCs) and ethnic minorities (8 HBCs). Other vulnerable groups such as the homeless, alcohol dependent individuals, tobacco smokers, injecting drug users and patients with diabetes have also been considered in a few HBCs.

It is noteworthy that major political instability notwithstanding, NTP structures in Iraq have been maintained at national and governorate levels. TB control services were provided whenever and wherever possible, depending on the security situation. Among other known troubled areas, TB control activities have been successfully implemented in collaboration with various international partners in secured areas of Afghanistan, the eastern region of the Democratic Republic of the Congo and in Somalia. In the earthquake-affected regions of Azad Kashmir in Pakistan, NTP services were re-established quickly and successfully in 2006.

1 2007 AIDS epidemic update. Geneva, Joint United Nations Programme on HIV/AIDS and WHO, 2007 (UNAIDS/07.27E/JC1322E).

2 Interim policy on collaborative TB/HIV activities. Geneva, World Health Organization, 2004 (WHO/HTM/TB/2004.330; WHO/HTM/HIV/2004.1).

3 Refers to 41 countries that were identified as priorities at global level in 2002 and that account for 97% of estimated HIV-positive TB cases globally, plus 22 additional countries that UNAIDS has defined as having a generalized HIV epidemic.

4 The WHO/IUATLD Global Project on Anti-tuberculosis Drug Resistance Surveillance. Anti-tuberculosis drug resistance in the world. Fourth global report. Geneva, World Health Organization, 2008 (WHO/HTM/TB/2008.394).

5 Guidelines for the programmatic management of drug-resistant tuberculosis. Geneva, World Health Organization, 2006 (WHO/HTM/TB/2006.361)

6 The Global MDR-TB and XDR-TB response plan 2007-2008. Geneva, World Health Organization, 2007 (WHO/HTM/STB/2007.387).