Methods
Monitoring progress in TB control (1995–2005)
Goals, targets and indicators for TB control
The targets and indicators for TB control, defined within the framework of the MDGs, have been supplemented and endorsed by the Stop TB Partnership (Table 1).1 These will be used to measure progress made under the Stop TB Strategy2, which extends and enhances the DOTS strategy (Tables 2, 3). The Global Plan to Stop TB3 describes how the Stop TB Strategy should be implemented over the decade 2006–2015.
This report focuses on the five principal indicators that are used to measure the implementation and impact of TB control: case detection and treatment success, and incidence, prevalence and deaths. The objective of reducing incidence is made explicit by MDG Target 8; the targets of 70% case detection and 85% treatment success were set by WHO’s World Health Assembly;4 the targets for prevalence and deaths are based on a resolution of the year 2000 meeting of the Group of Eight (G8) industrialized countries, held in Okinawa, Japan. The targets for case detection and treatment success should have been reached by the end of 2005. This report presents the best possible assessment, based on case reports to the end of 2005, of whether the targets were reached in the world as a whole, and in each WHO region and country.
Data collection and verification
Every year, WHO requests information from national TB control programmes (NTPs) or relevant public health authorities in 212 countries or territories5 via a standard data collection form.6 The latest form was distributed in mid-2006. The section dealing with monitoring and surveillance asked for data including the following: whether the elements of DOTS and the Stop TB Strategy were being implemented during 2005; DOTS population coverage in 2005; TB case notifications in 2005 (from DOTS and non-DOTS areas, each with 12 categories; new pulmonary smear-positive cases by age and sex); TB patients tested for HIV and MDR-TB in 2005; and treatment outcomes for TB patients registered during 2004 (DOTS, non-DOTS, HIV-infected, each with 7 categories) and MDR-TB patients registered during 2002 (GLC-approved and other, each with 3 categories). The main case definitions are given in Table 5.
The data collection form used in the WHO European Region asked for additional data, including a breakdown of all TB cases by age, geographical origin (e.g. born outside country/non-citizen) and mycobacterial culture result; all TB cases by HIV serostatus and age; and HIV-positive TB cases by sex and age. For NTPs in the 63 countries that account for 98% of all HIV-infected TB patients, the data collection form was extended to obtain further information about TB linked to HIV infection (see Collaborative TB/HIV activities).
As NTPs respond to WHO, they are also asked to update information for earlier years if they are able to do so. As a result of such revisions, the data (case notifications, treatment outcomes, etc.) presented in this report for years preceding 2004 and 2005 may differ from those published in previous reports.
The standard data collection form is used to compile aggregated national data. The process of national and international reporting is distinct from WHO’s recommendations about procedures for recording and reporting data by NTPs within countries, from district level upwards.7
Completed forms are collected and reviewed at all levels of WHO, by country offices, regional offices and at headquarters. An acknowledgement form that tabulates all submitted data is sent back to the NTP correspondent in order to complete any missing responses and to resolve any inconsistencies. Then, using the complete set of data for each country, we construct a profile that tabulates all key indicators, including epidemiological and financial data and estimates, and this too is returned to each NTP for review. In the WHO European Region only, data collection and verification are performed jointly by the regional office and a WHO collaborating centre, EuroTB (Paris). EuroTB subsequently publishes an annual report with additional analyses, using more detailed data for the European Region (www.eurotb.org).
High-burden countries, WHO regions and other subregions of the world
Much of the data submitted to WHO is shown, country by country, in the annexes of this report. The analysis and interpretation that precede these annexes focus on 22 HBCs and the six WHO regions. The 22 HBCs account for approximately 80% of the estimated number of new TB cases (all forms) arising worldwide each year. These countries are the focus of intensified efforts in DOTS expansion (Annex 1). The HBCs are not necessarily those with the highest incidence rates per capita; many of the latter are medium-sized African countries with high rates of TB/HIV coinfection. The WHO regions are the African Region, the Region of the Americas, the Eastern Mediterranean Region, the European Region, the South-East Asia Region and the Western Pacific Region. All essential statistics are summarized for each of these regions and globally. However, to make clear the differences in epidemiological trends within regions, we divide the African Region into countries with low and high rates of HIV infection (“high” is an infection rate of ≥4% in adults aged 15–49 years, as estimated by UNAIDS in 2004). We also distinguish central from eastern Europe (countries of the former Soviet Union plus Bulgaria and Romania), and combine western European countries with the other established market economies. The countries within each of the resulting nine subregions are listed in the legend to Figure 5.
Implementation of DOTS and the Stop TB Strategy
DOTS remains central to the public health approach to TB control, which is now presented as the Stop TB Strategy (Table 2). Before the launch of the strategy during 2006, NTPs reporting to WHO were classified as either DOTS or non-DOTS, based on the elements listed in Tables 2 and 3. To be classified as DOTS in this report, a country must have officially accepted and adopted the strategy in 2005, and must have implemented the four technical components of DOTS in at least part of the country (Annex 2). Based on NTP responses to standard questions about policy – and usually on further discussion with the NTP – we have accepted or revised each country’s own determination of its DOTS status.
DOTS coverage
Coverage is defined as the percentage of the national population living in areas where health services have adopted DOTS. “Areas” are the lowest administrative or basic management units8 in the country (townships, districts, counties, etc.). If an area (with its one or more health facilities) is considered by the NTP to have been a DOTS area in 2005, then all the cases registered and reported by the NTP in that area are considered DOTS cases, and the population living within the boundaries of that area counts towards the national DOTS coverage. In some cases, treatment providers that are not following DOTS guidelines (e.g. private practitioners, or public health services outside the NTP such as those within prisons) notify cases to the NTP. These cases are considered non-DOTS cases, even if they are notified from within DOTS areas. However, when certain groups of patients treated by DOTS services receive special regimens or management (e.g. nomads placed on longer courses of treatment), these are considered DOTS cases. Where possible, additional information about these special groups of patients is provided in the country notes in Annex 2. Ideally, the DOTS coverage in any one year should be calculated by evaluating the number of person-years covered in each quarter, and then summing across the four quarters of the year (although some countries simply report the population coverage achieved by the end of the year).
DOTS coverage calculated as described above is a crude indicator of the actual proportion of people who have access to DOTS services, but it is easy to calculate and is most useful during the early stages of DOTS expansion. As a measure of patient access to diagnosis and treatment under DOTS, coverage is an approximation, and usually an overestimate. Where countries are able to provide more precise information about access to DOTS services, this information is reported in the country notes of Annex 2. The case detection rate (defined below) is a more precise measure of DOTS implementation but is also more demanding of data.
Estimating TB incidence, prevalence and death rates
Estimates of TB incidence, prevalence and deaths are based on a consultative and analytical process. They are revised annually to reflect new information gathered through surveillance (case notifications and death registrations) and from special studies (including surveys of the prevalence of infection and disease). The details of estimation are described elsewhere.9 10 11 In brief, estimates of incidence (number of new cases arising each year) for each country are derived using one or more of four approaches, depending on the available data:
incidence = case notifications/proportion of cases detected (1)
incidence = prevalence/duration of condition (2)
incidence = annual risk of infection x Styblo coefficient (3)
incidence = deaths/proportion of incident cases that die (4)
The Stýblo coefficient in equation (3) is taken to be a constant, with an empirically derived value in the range 40–60, relating risk of infection (% per year) to the incidence of sputum smear-positive cases (per 100 000 per year). Given two of the quantities in any of these equations, we can calculate the third, and these formulae can be rearranged to estimate incidence, prevalence and death rates. The available data differ from country to country, and not all methods can be applied in every country.
Among all new, HIV-negative TB patients, 45% are assumed to be smear-positive (ranging uniformly between 40% and 50% in uncertainty analysis). Among HIV-positive TB patients the fraction is smaller (35%, range 30–40%). Because most NTPs still do not routinely test TB patients for HIV infection, we have used, for all countries, an indirect estimate of the prevalence of HIV among new TB patients, calculated from:
prevalence of HIV in new TB patients = [PHIVX IRR] / [1+PHIV(IRR-1)] (5)
where PHIV is HIV prevalence in the adult population (15–49 years) and IRR is the incidence rate ratio, i.e. the TB incidence rate in HIV-infected adults divided by the TB incidence rate in HIV-uninfected adults. IRR takes values of 30 (range 21–39, with a triangular distribution in uncertainty analysis) for the established market economies and 6.0 (range 3.5–8.0) for all other countries.12
For each country, estimates of incidence for each year during the period 1995–2005 were made as follows. We first selected a reference year for which we have a best estimate of incidence; this may be the year in which a survey was carried out, or the year for which incidence was first estimated. We then use the series of case notifications (all new and relapse cases) to determine how incidence changed before and after that reference year. The time series of estimated incidence rates is constructed from the notification series in one of two ways: if the rate of change of case notifications is roughly constant through time, we fitted exponential trends to the notification series (subregions Africa low-HIV, Latin America, South-East Asia, Western Pacific); if the rate varies through time (subregions Africa high-HIV, Central Europe, Eastern Europe, Eastern Mediterranean, Established Market Economies), we used a three-year moving average of the notification rates. If the notifications for any country are considered to be an unreliable guide to trend (e.g. because reporting effort is known to have changed; or because reports are clearly erratic, changing in a way that cannot be attributed to TB epidemiology), we applied the aggregated trend for all other countries from the same epidemiological region that have reliable data. For some countries, we used an assessment of the trend in incidence based on risk of infection derived from other sources (tuberculin surveys for China and Nepal). For those countries that have no reliable data from which to assess trends in incidence (e.g. for countries such as Iraq and Pakistan, for which data are hard to interpret, and which are atypical within their own regions), we assumed that incidence is stable.
Estimates of incidence form the denominator of the case detection rate. Trends in incidence are governed by underlying epidemiological processes, modified by control programmes. The impact of control on prevalence is determined by the trend in incidence and by the estimated reduction in the duration of the condition, e.g. smear-positive disease.
The prevalence of TB is calculated from the product of incidence and duration of disease (rearranging equation 2), and the TB mortality rate from the product of incidence and case fatality (proportion of incident cases that ever die from TB; equation 4). The duration of disease and the case fatality are estimated, country by country, for patients treated within or outside DOTS programmes and for patients who receive no recognized anti-TB treatment. Because the duration of disease and case fatality are typically shorter for patients treated under DOTS than for patients who are treated elsewhere or untreated, the average duration of disease and average case fatality decrease as the proportion of patients treated under DOTS increases.13 14 15
Where population sizes are needed to calculate TB indicators, we use the latest revision of estimates provided by the United Nations Population Division.16 These estimates sometimes differ from those made by the countries themselves, some of which are based on more recent census data. The estimates of some TB indicators, such as the case detection rate, are derived from data and calculations that use only rates per capita, and discrepancies in population sizes do not affect these indicators. Where rates per capita are used as a basis for calculating numbers of TB cases, these discrepancies sometimes make a difference. Some examples of important differences are given in the country notes in Annex 2.
Because accurate measurement is crucial in the evaluation of epidemic trends, Table 4 provides some methodological guidance, based on a review by a WHO panel of experts in June 2006. Table 4 can be read in conjunction with the list of countries that have done, or are planning, infection (tuberculin) and disease prevalence surveys, and with the set of countries that now register deaths by cause and provide these data to WHO (including TB; Annex 3).
Case notification and case detection
Sputum smear-positive cases are the focus of DOTS programmes because they are the principal sources of infection to others, because sputum smear microscopy is a highly specific (if somewhat insensitive) method of diagnosis, and because patients with smear-positive disease typically suffer higher rates of morbidity and mortality than smear-negative patients. As a measure of the quality of diagnosis, we calculate the proportion of new smear-positive cases out of all new pulmonary cases, which has an expected value of at least 65% in areas with negligible HIV prevalence.17
The term “case notification”, as used here, means that TB is diagnosed in a patient and is reported within the national surveillance system, and then to WHO. While the emphasis is on new smear-positive cases, we also present the numbers of all TB cases reported – smear-positive and smear-negative pulmonary cases – in addition to those in whom extrapulmonary disease is diagnosed. The number of cases notified in any year is the sum of new and relapse cases. Case reports that represent a second registration of the same patient/episode (i.e. re-treatment after failure or default) are presented separately.
The case detection rate is calculated as the number of cases notified divided by the number of cases estimated for that year, expressed as a percentage. Detection is presented in four main ways: (a) for new smear-positive cases (excluding relapses); (b) for all new cases (all clinical forms of TB, excluding relapses); (c) for DOTS programmes only; or (d) for cases notified from all sources (DOTS and non-DOTS areas). For new smear-positive cases aggregated as in (c) and (d):
DOTS case detection rate = annual new smear-positive notifications (DOTS)/estimated annual new smear-positive incidence (country) (6)
Case detection rate = annual new smear-positive notifications (country)/estimated annual new smear-positive incidence (country) (7)
The target of 70% case detection applies to the DOTS case detection rate in formula (6). Even when a country is not 100% DOTS, we use the incidence estimated for the whole country as the denominator of the case detection rate, as in equation (6). The DOTS detection rate and the case detection rate for the whole country are identical when a country reports only from DOTS areas. This generally happens when DOTS coverage is 100%, but in some countries where DOTS is implemented in only part of the country, no TB notifications are received from the non-DOTS areas. Furthermore, in some countries where DOTS coverage is 100%, patients may seek treatment from non-DOTS providers that, in some cases, notify TB cases to the national authorities.
Although these indices are termed “rates”, they are actually ratios. The number of cases notified is usually smaller than the estimated incidence because of incomplete coverage by health services, under-diagnosis, or deficient recording and reporting. However, the calculated detection rate can exceed 100% if case-finding has been intense in an area that has a backlog of existing cases, if there has been over-reporting (e.g. double-counting) or over-diagnosis, or if estimates of incidence are too low. If the expected number of cases per year is very low (e.g. less than one), the case detection rate can vary markedly from year to year because of chance. Whenever this index comes close to or exceeds 100%, we attempt to investigate, as part of the joint planning and evaluation process with NTPs, which of these explanations is correct.
The ratio of the DOTS case detection rate to coverage is an estimate of the case detection rate within DOTS areas (as distinct from the case detection rate nationwide), assuming that the TB incidence rate is homogeneous across counties, districts, provinces or other administrative units. The detection rate within DOTS areas should exceed 70% as DOTS coverage increases within any country. The value of this indicator is low when the DOTS programme has been poorly implemented, when access to DOTS is limited, or when TB incidence in DOTS areas has been overestimated. Changes in the value of this ratio through time are a measure of changes in the quality of TB control, after the DOTS programme has been established.
Outcomes of treatment
Treatment success in DOTS programmes is the percentage of new smear-positive patients who are cured (negative on sputum smear examination), plus the percentage that complete a course of treatment, without bacteriological confirmation of cure (Table 5). Cure and completion are among the six mutually exclusive treatment outcomes.18 The sum of cases assigned to these outcomes, plus any additional cases registered but not assigned to an outcome, adds up to 100% of cases registered (i.e. the treatment cohort).
We also compare the number of new smear-positive cases registered for treatment (for this report, in 2004) with the number of cases notified as smear-positive (also in 2004). All notified cases should be registered for treatment, and the numbers notified and registered should therefore be the same (discrepancies arise, for example, when subnational reports are not received at national level). If the number registered for treatment is not provided, we take as the denominator for treatment outcomes the number notified for that cohort year. If the sum of the six outcome categories is greater than the number registered (or the number notified), we use this sum as the denominator.
The number of patients presenting for a second or subsequent course of treatment, and the outcome of further treatment, are indicative of NTP performance and levels of drug resistance. We present in this report, where data are available, the numbers of patients registered for re-treatment, and the outcomes of re-treatment, for each of four registration categories: smear-positive re-treatment after relapse; failure; default; and other re-treatment (including pulmonary smear-negative and extrapulmonary).
The assessment of treatment outcomes for a given calendar year always lags case notifications by one year, to ensure that all patients registered during that calendar year have completed treatment. For MDR-TB patients, who have longer treatment regimens, the lag is three years. A DOTS country must report treatment outcomes, unless it is newly-classified as DOTS, in which case it would take an additional year to report outcomes from the first cohort of patients treated.
NTPs should ensure high treatment success before expanding case detection. The reason is that a proportion of patients given less than a fully-curative course of treatment remain chronically infectious and continue to spread TB. Thus DOTS programmes must be shown to achieve high cure rates in pilot projects before attempting countrywide coverage.
Footnotes
1 Dye C et al. Targets for global tuberculosis control. International Journal of Tuberculosis and Lung Disease, 2006, 10:460-462.
2 Raviglione MC, Uplekar MW. WHO's new Stop TB Strategy. Lancet, 2006, 367:952-955.
3 The Global Plan to Stop TB, 2006-2015. Geneva, Stop TB Partnership and World Health Organization, 2006, 10:460-462.
4 Resolution WHA44.8. Tuberculosis control programme. In: Handbook of resolutions and decisions of the World Health Assembly and the Executive Board. Volume III, 34d ed. (1985-1992). Geneva, World Health Organization, 1993 (WHA44/1991/REC/1).
5 Serbia and Montenegro were treated as separate countries from 2005 onwards, increasing the 2004 total by one.
6 Posted at www.who.int/tb/country/en/
7 Revised procedures for recording and reporting at district level are described at www.who.int/tb/dots/r_and_r_forms/en/index.html
8 The basic management unit is defined in terms of management, supervision, and monitoring responsibility. It may have several treatment facilities, one or more laboratories, and one or more hospitals. The defining aspect is the presence of a manager or coordinator who oversees TB control activities for the unit and who maintains a master register of all TB patients being treated, which is used to monitor the programme and report on indicators to higher levels.
9 Dye C et al. Global burden of tuberculosis: estimated incidence prevalence and mortality by country. Journal of the American Medical Association, 1999, 282:677-686.
10 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.
11 Dye C et al. Evolution of tuberculosis control and prospects for reducing tuberculosis incidence, prevalence, and deaths globally Journal of the American Medical Association, 2005, 293:2767-2775.
12 Corbet EL et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Archives of Internal Medicine, 2003, 163:1009-1021. The estimated IRR of 30 for the established market economies was reduced from the original estimate of 60 based on 2001 data published by the United States Centers for Disease Control and Prevention. The estimate of 6 for all other countries was reviewed with a new compilation of data, made in January 2007, from approximately 200 studies. The new analysis gave a point estimate of IRR close to 6, on which basis we retained the original estimate used by Corbett et al. Further details are available from tbdocs@who.int
13 Dye C et al. Global burden of tuberculosis: estimated incidence, prevalence and mortality by country. Journal of the American Medical Association, 1999, 282:677-686.
14 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.
15 Dye C et al. Evolution of tuberculosis control and prospects for reducing tuberculosis incidence, prevalence, and deaths globally. Journal of the American Medical Association, 2005, 293:2767-2775.
16 World population prospects - the 2002 revision. New York, United Nations Population Division, 2003.
17 Tuberculosis handbook. Geneva, World Health Organization, 1998 (WHO/TB/98.253).
18 Treatment of tuberculosis: guidelines for national programmes. 3rd ed. Geneva, World Health Organization, 2003 (WHO/CDS/TB/2003.313).