Tuberculosis (TB)

Methods

Monitoring progress in TB Control

Goals, target and indicators for TB control

The target 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 Strategy, 2 which extends and enhances the DOTS strategy (Tables 2, 3 ). The Global Plan 3 describes how the Stop TB Strategy should be implemented over the next 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 for case detection and treatment success have been 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.

Data collection and verification

Every year, WHO requests information from national TB control programmes (NTPs) or relevant public health authorities in 211 countries or territories via a standard data collection form. The latest form was distributed in mid-2005. The section dealing with monitoring and surveillance asked for data including the following: whether DOTS was implemented during 2004; DOTS population coverage in 2004; TB case notifications in 2004; TB patients tested for HIV and MDR-TB in 2003–2004, and treatment outcomes for TB patients registered during 2003, following definitions given in Table 4. The most recent form can be found here.

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 2003 and 2004 could 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. 5

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 DOTS classification

Much of the data submitted to WHO is shown, country by country, in the annexes of this report. The analysis and interpretation that precedes 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 greater than an estimated infection rate of 4% in adults aged 15–49 years). 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 regions are listed in the legend to Figure 5.

DOTS classification

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 classified their programmes as either DOTS or non-DOTS, referring to 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 2004, 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 – WHO has 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 management units 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 2004, 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, 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 and from special studies, such as surveys of the prevalence of infection and disease. The details of estimation are described elsewhere.) 6 7 8 In brief, estimates of incidence (number of new cases per 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 but include case notifications and death records (from routine surveillance and vital registration), and measures of the prevalence of infection and disease (from population-based surveys).

For each country, estimates of incidence for each year during the period 1995–2004 are made as follows. We first select 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 incidence is roughly constant through time, we fit exponential trends to the notifications; if the rate varies through time (eastern Europe, central Europe and high-HIV Africa), we use 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 apply the aggregated trend for all other countries from the same epidemiological region that have reliable data. For some countries (China, Indonesia and Nepal), we have used an assessment of the trend in incidence based on risk of infection derived from other sources (tuberculin surveys for China and Nepal; disease prevalence surveys for Indonesia). For those countries that have no reliable data from which to assess trends in incidence (e.g. for countries such as Iraq, for which data are hard to interpret, and which are atypical within their own regions), we assume that incidence is stable. Further details are available at www.who.int/tb .

Since most countries have not yet measured HIV infection rates in TB patients directly, we have used, for all countries, an indirect estimate derived from estimates of the HIV prevalence in the general population, and from the incidence rate ratio (the TB incidence rate in HIV-infected people divided by the incidence rate in HIV-uninfected people). 9 The prevalence of MDR-TB among untreated and previously treated TB patients has also been estimated in separate studies. 10 11

Estimates of incidence form the denominator of the case detection rate. Trends in incidence are determined by underlying epidemiological processes, modified by control programmes.

The prevalence of TB is calculated from the product of incidence and duration of disease, and the TB mortality rate from the product of incidence and case fatality (proportion of incident cases that ever die from TB). 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 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. 12 13 14

Where population sizes are needed to calculate TB indicators, we use the latest revision of estimates provided by the United Nations Population Division. 15 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.

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 65–80% in areas with negligible HIV prevalence. 16

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 given primarily as the sum of new and relapse cases, i.e. the sum of new (or presumed to be new) episodes of TB. Case reports that represent a second registration of the same patient/episode (i.e. re-treatment after failure or default) are presented separately.

The term “case detection”, as used here, means that TB is diagnosed in a patient and is reported within the national surveillance system, and then to WHO. 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: (i) for new smear-positive cases (excluding relapses), (ii) for all new and relapse cases (i.e. all forms of TB), (iii) for DOTS programmes only, or (iv) for cases notified from all sources. The next section describes, as part of a special investigation carried out for this report, case detection based on diagnosis by culture. For new smear-positive cases aggregated as in (iii) and (iv):

DOTS case detection rate = annual new smear-positive notifications (DOTS)/estimated annual new smear-positive incidence (country) (5)

case detection rate = annual new smear-positive notifications (country)/estimated annual new smear-positive incidence (country) (6)

The target of 70% case detection applies to the DOTS case detection rate in formula (5). 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 (5). 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 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 chronic 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 (especially if it is 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. Where the value of this indicator is much lower, it is clear that the DOTS programme has been poorly implemented, at least in some parts of the designated DOTS area. 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.

Comparison of methods for evaluating case detection

Since sputum smear microscopy is an insensitive method of diagnosing pulmonary TB, and since culture and other new diagnostic methods are likely to be used more frequently in the near future, we have continued to explore alternative methods of evaluating case detection and the outcome of treatment. 17

We compared case detection rates based on smears and cultures in two steps. First, by examining the results of smears and cultures for individual patients with pulmonary TB in 25 European countries, we obtained an estimate of the proportion of culture-positive patients that are also smear-positive. Second, we used this estimate in the following formula to derive culture-positive incidence rates for European countries:

culture-positive incidence = smear-positive incidence/proportion culture-positive patients that are also smear-positive (7)

These estimated incidence rates are the denominators of the culture-positive case detection rates for countries in the European region. The numerators are the numbers of pulmonary TB patients reported to be positive by culture.

Broadening the analysis, we also compared the smear-positive detection rates (for countries in the European and other regions) with the detection rates of all laboratory-confirmed cases of TB (i.e. smear-positive and/or culture-positive) and the detection rates of all cases of TB (new and relapse, pulmonary and extrapulmonary, diagnosed by smear, culture, radiography or by clinical examination).

Outcomes of treatment

Treatment success in DOTS programmes is the percentage of new smear-positive patients that are cured (negative on sputum smear examination), plus the percentage that complete a course of treatment, without bacteriological confirmation of cure (Table 4). 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 2003) with the number of cases notified as smear-positive (also in 2003). 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 the numbers of patients registered for re-treatment, and the outcomes of re-treatment, for each of three registration categories: re-treatment after relapse, failure and default. However, some countries do not yet compile data on cases registered for re-treatment after failure and default separately at national level. Furthermore, some countries do not have outcome data for each of these re-treatment case categories.

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. 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

1Dye C et al. Targets for global tuberculosis control. International Journal of Tuberculosis and Lung Disease, 2006 [in press].

2Raviglione MC, Uplekar MW. The new Stop TB Strategy of WHO. Lancet 2006; 367: 877-78 - Register free to download articles.

3The Global Plan to Stop TB, 2006–2015 . Geneva, World Health Organization, 2006 (WHO/HTM/STB/2006.35).

4Resolution WHA44.8. Tuberculosis control programme. In: Handbook of resolutions and decisions of the World Health Assembly and the Executive Board. Volume III, 3rd ed. (1985–1992). Geneva, World Health Organization, 1993 (WHA44/1991/REC/1).

5Revised procedures for recording and reporting at district level, to be field-tested during 2006, are described at www.who.int/tb/publications/recording_and_reporting_draft/en/index.html

6Dye C et al. Global burden of tuberculosis: estimated incidence, prevalence and mortality by country. Journal of the American Medical Association, 1999, 282:677–686.

7Corbett EL et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Archives of Internal Medicine, 2003, 163:1009–1021.

8Dye 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.

9Corbett EL et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Archives of Internal Medicine, 2003, 163:1009–1021.

10Dye C et al. Worldwide incidence of multidrug-resistant tuberculosis. Journal of Infectious Diseases 2002, 185:1197–1202.

11Zignol M et al. Global incidence of multidrug-resistant tuberculosis [submitted for publication].

12Dye C et al. Global burden of tuberculosis: estimated incidence, prevalence and mortality by country. Journal of the American Medical Association, 1999, 282:677–686.

13Corbett EL et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Archives of Internal Medicine, 2003, 163:1009–1021.

14Dye 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.

15World population prospects – the 2002 revision. New York, United Nations Population Division, 2003.

16Tuberculosis handbook. Geneva, World Health Organization, 1998 (WHO/TB/98.253).

17A comparison of treatment outcomes evaluated by smear and culture conversion is in Global tuberculosis control. WHO report 2001. Geneva, World Health Organization (WHO/CDS/TB/2001.287), p.22.

18Treatment of tuberculosis: guidelines for national programmes. 3rd ed. Geneva, World Health Organization, 2003 (WHO/CDS/TB/2003.313).

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