Measuring tuberculosis burden, trends, and the impact of control programmes.

The targets for tuberculosis control, framed within the United Nations' Millennium Development Goals, are to ensure that the incidence per head of tuberculosis is falling by 2015, and that the 1990 prevalence and mortality per head are halved by 2015. In monitoring progress in tuberculosis control, the ultimate aim for all countries is to count tuberculosis cases (incidence) accurately through routine surveillance. Disease prevalence surveys are costly and laborious, but give unbiased measures of tuberculosis burden and trends, and are justified in high-burden countries where many cases and deaths are missed by surveillance systems. Most countries in which tuberculosis is highly endemic do not yet have reliable death registration systems. Verbal autopsy, used in cause-of-death surveys, is an alternative, interim method of assessing tuberculosis mortality, but needs further validation. Although several new assays for Mycobacterium tuberculosis infection have recently been devised, the tuberculin skin test remains the only practical method of measuring infection in populations. However, this test typically has low specificity and is therefore best used comparatively to assess geographical and temporal variation in risk of infection. By 2015, every country should be able to assess progress in tuberculosis control by estimating the time trend in incidence, and the magnitude of reductions in either prevalence or deaths.

Tuberculosis epidemiology in six provinces of Vietnam after the introduction of the DOTS strategy.

SETTING: Six provinces in Vietnam where the DOTS strategy was introduced in 1989. OBJECTIVE: To assess the impact of improved tuberculosis (TB) control on TB epidemiology in Vietnam. METHODS: Data from the surveillance system in the period 1990-2003 were analysed to assess trends of notification rates and the mean ages of notified cases. Data from repeated tuberculin surveys in the period 1986-2002 were estimated to assess the prevalence of TB infection, the annual risk of infection and its trend using various cut-off points in those with and without bacille Calmette-Guérin (BCG) scar. RESULTS: Age-standardised notification rates in the period 1996-2003 declined significantly, by 2.6% to 5.9% per year, in five provinces. However, in four provinces notification rates in the age group 15-24 years increased significantly, by 4.5% to 13.6% per year, during this period. The mean age of newly diagnosed patients with smear-positive TB increased up to 1995 but decreased thereafter. The annual risk of TB infection showed a significant annual decrease (4.9% per year) in one province in surveys performed between 1986 and 1997, and in two provinces (6.6% and 4.7%) in surveys conducted between 1993 and 2002. CONCLUSION: These data suggest limited impact to date of the DOTS strategy in Vietnam.

Evaluation of sputum smear microscopy in the National Tuberculosis Control Programme in the north of Vietnam.

OBJECTIVE: To assess the yield of sputum smear microscopy and sex differences in the National Tuberculosis Control Programme in the north of Vietnam. METHODS: Review of registers of 30 randomly selected laboratories (26 district, 4 provincial level). RESULTS: The average daily workload per technician was 4.4 examinations in district and 5.3 examinations in provincial laboratories. To find one smear-positive case, 9.7 suspects were examined and 29.3 smears done. The smear-positive rate (mean 10.3%) was higher among men (11.6%) than among women (8.4%, P < 0.001). There were more men than women among tuberculosis (TB) suspects (male:female ratio 1.36, 95%CI 1.19-1.54), but even more so among smear-positive patients (1.89, 95%CI 1.64-2.14), irrespective of specimen quality and number of smears examined. Three smears were examined for 18,055 suspects (61.7%). The incremental gain was 33.5% and 4.9% for the second and third smear examination, respectively; 186 (95%CI 160-221) smears needed to be examined to find one additional case of TB with a third serial examination. CONCLUSION: The diagnostic process seemed generally efficient. The male:female ratios suggest higher TB incidence in men rather than lower access to TB facilities for women. The third smear examination could be omitted.

[An outbreak of multiresistant tuberculosis from Eastern Europe in the Netherlands]. / Een uitbraak van multiresistente tuberculose uit Oost-Europa in Nederland.

Infectious multiresistant pulmonary tuberculosis was diagnosed in a 24-year-old woman from an Eastern European country who resided in the Netherlands illegally. Her chest X-ray showed extensive cavitating lesions in both lungs. The patient was infectious for a long time and contact investigation revealed 2 other cases of multiresistant tuberculosis, her boyfriend aged 39 and his father, aged 58 years. Transmission from the index case was confirmed by DNA fingerprinting. Seven contacts had a latent tuberculosis infection. All 3 tuberculosis patients were successfully treated, while a number of the infected contacts received preventive treatment. Multiresistant tuberculosis is on the rise in Eastern Europe. It is a serious disease with a high mortality rate despite treatment and has considerable social implications. This outbreak emphasises the necessity of maintaining an efficient tuberculosis control network in low incidence countries, such as the Netherlands. This is the first time an outbreak of multiresistant tuberculosis of this magnitude is described in the Netherlands.

Establishment and development of the National Tuberculosis Control Programme in Vietnam.

OBJECTIVE: To describe the establishment and development of the National Tuberculosis Control Programme (NTP) of Vietnam. METHODS: Data were obtained from the surveillance system established by the new NTP in 1986 and based on the principles now described as the WHO DOTS strategy. RESULTS: The proportion of districts covered by the NTP increased from 40% in 1986 to almost 100% in 2000. The proportion of communes applying NTP guidelines increased from 18% in 1986 to 99.8% in 2000. The total number of tuberculosis cases notified increased from 8737 in 1986 to 89 792 in 2000. Most of these are new smear-positive cases. Based on WHO estimations of the incidence rate, the proportion of new smear-positive cases detected and put on short-course treatment has been over 70% since 1996. Reported cure rates with short-course chemotherapy are consistently over 85%. CONCLUSIONS: DOTS is feasible in a low-income, high-burden country. The main reasons for success were political commitment, a well-functioning health network, integration of tuberculosis control into the general health service at district level, a continuous supply of drugs and effective external support. Major challenges are long-term financial support, expansion to remote areas and vulnerable groups, definition of the role of the private sector, and future developments of the HIV epidemic and multidrug resistance.

[Centenary of the Royal Dutch Central Association for the Prevention of Tuberculosis]. / Honderd jaar Koninklijke Nederlandse Centrale Vereniging tot bestrijding der tuberculose (KNCV).

The Royal Dutch Tuberculosis Association (Koninklijke Nederlandse Centrale Vereniging tot bestrijding der Tuberculose (KNCV)) was founded in 1903. Since then various interventions against tuberculosis have been introduced on the basis of medical and technological opportunities and in response to the epidemiological situation. The introduction of effective drugs during the 1940s and 1950s was by far the most important development and led to a sharp decline in the annual rate of infection and to the disappearance of tuberculosis as a common disease. Following the appointment of the independent National Policy Committee for Tuberculosis Control, Royal Dutch Tuberculosis Association could concentrate on its innovating tasks: the development of new interventions based on epidemiological data and scientific research.

European framework for tuberculosis control and elimination in countries with a low incidence. Recommendations of the World Health Organization (WHO), International Union Against Tuberculosis and Lung Disease (IUATLD) and Royal Netherlands Tuberculosis Association (KNCV) Working Group.

As countries approach the elimination phase of tuberculosis, specific problems and challenges emerge, due to the steadily declining incidence in the native population, the gradually increasing importance of the importation of latent tuberculosis infection and tuberculosis from other countries and the emergence of groups at particularly high risk of tuberculosis. Therefore, a Working Group of the World Health Organization (WHO), the International Union Against Tuberculosis and Lung Disease (IUATLD) and the Royal Netherlands Tuberculosis Association (KNCV) have developed a new framework for low incidence countries based on concepts and definitions consistent with those of previous recommendations from WHO/IUATLD Working Groups. In low-incidence countries, a broader spectrum of interventions is available and feasible, including: 1) a general approach to tuberculosis which ensures rapid detection and treatment of all the cases and prevention of unnecessary deaths; 2) an overall control strategy aimed at reducing the incidence of tuberculosis infection (risk-group management and prevention of transmission of infection in institutional settings) and 3) a tuberculosis elimination strategy aimed at reducing the prevalence of tuberculosis infection (outbreak management and provision of preventive therapy for specified groups and individuals). Government and private sector commitment towards elimination, effective case detection among symptomatic individuals together with active case finding in special groups, standard treatment of disease and infection, access to tuberculosis diagnostic and treatment services, prevention (e.g. through screening and bacille Calmette-Guéria immunization in specified groups), surveillance and treatment outcome monitoring are prerequisites to implementing the policy package recommended in this new framework document.

The impact of immigration on the elimination of tuberculosis in The Netherlands: a model based approach.

OBJECTIVE: To determine whether elimination of tuberculosis in the Dutch population can be achieved by the year 2030, taking into account the impact of immigration. METHODS: The incidence of tuberculosis (all forms) in the period 1970 to 2030 was estimated using a life-table model for the Dutch population without the impact of immigration. The influence of immigration on tuberculosis incidence among the Dutch was modelled using four immigrant scenarios, distinguished by the assumed contact rate between immigrants and the Dutch population, and by different projections (middle, upper) of the future size of the immigrant population in The Netherlands. RESULTS: The incidence of smear-positive tuberculosis among the Dutch is projected to be 1.4 per million in the scenario without the influence of immigrant cases, and ranging from 3.8 to 11.8 per million in the four immigrant scenarios. In all immigrant scenarios, the prevalence of tuberculosis infection will continue to decline and be less than 1% by the year 2030. At least 60% of Dutch tuberculosis cases in the year 2030 are expected to be the result of transmission from a foreign source case. CONCLUSION: Using a prevalence of tuberculosis infection of less than 1% as the elimination criterion, tuberculosis will probably be eliminated from the indigenous Dutch population by 2030. However, the incidence of smear-positive tuberculosis is expected to remain higher than 1 per million, and the majority of new tuberculosis cases among the Dutch may be attributable to recent infection from a foreign source case.

Risk of tuberculosis infection and tuberculous meningitis after discontinuation of Bacillus Calmette-Guerin in Beijing.

In Beijing, the notification rate of smear-positive tuberculosis (TB) has been below 20 per 100,000 since 1986, and continues to decline. To accurately measure the risk of TB infection in a population in which the results of tuberculin skin testing were not confounded by vaccination with Bacillus Calmette-Guerin (BCG), BCG vaccination at birth was discontinued from 1988 in Shun-yi County. In 1995, the prevalence of TB infection among 12,836 primary school children aged 6 to 7 yr and without BCG scars was 1.4%, giving an estimated annual risk of infection of 0.19% (95% confidence interval: 0.16 to 0.22%). The prevalence of TB infection in children aged 5 to 9 yr in Beijing in 1950 was 46%. The number of cases of tuberculous meningitis did not increase after discontinuation of BCG. We conclude that discontinuation of BCG had no detectable harmful effects, and that control of TB in Beijing has markedly reduced the prevalence of TB infection since 1950.

Defaulting from tuberculosis treatment in The Netherlands: rates, risk factors and trend in the period 1993-1997.

The aim of this study was to assess the rate of defaulting from treatment among tuberculosis patients diagnosed in the Netherlands in the period 1993-1997, whether risk groups for defaulting can be identified at the start of treatment and the trend of defaulting over time. The Netherlands Tuberculosis Register provided data on all patients diagnosed in the Netherlands during the period 1993-1997. Defaulting probabilities were determined using Kaplan-Meier survival analysis and risk factors were identified with Cox's proportional hazard analysis. Of 7,529 patients with reported treatment outcome, 718 (10%) defaulted or left the country within 1 yr after starting treatment. Defaulting probabilities were 9% (95% confidence interval (CI) 8-10%) among 5,256 patients in low-risk groups, 17% (95% CI 14-19%) among 1,437 asylum seekers and 29% (95% CI 24-34%) among 836 patients in other high-risk groups (other recent immigrants, illegal immigrants, the homeless, prisoners and nationals from Eastern Europe). Defaulting probabilities decreased over time from 12% in 1993 to 7% in 1997. Risk groups for defaulting can be recognized at the start of treatment. The decreasing defaulting probabilities were probably due in part to shortening treatment from 9 to 6 months and improved follow-up of asylum seekers. However, additional measures are needed to reduce defaulting among the homeless, recent immigrants, illegal immigrants and prisoners.

The design of multi-stage tuberculin surveys: some suggestions for sampling.

SETTING: Tuberculin surveys of children to estimate national or regional infection prevalences are commonly designed as multi-stage surveys. These surveys require strategies for the efficient sampling of sub-units at each stage. OBJECTIVES: To develop guidelines for sampling in tuberculin surveys. DESIGN: Sampling theory was used to develop a simple and efficient sampling strategy for planning and analysing tuberculin surveys. The issue of sample sizes is considered. RESULTS: Formulae for the calculation of infection prevalences and their confidence intervals are developed. Sample sizes are discussed. CONCLUSION: We recommend that districts be sampled using sampling proportional to size, in which larger units have a larger probability of being included in the sample. Schools are sampled next using simple random sampling, where each school within a district has the same probability of being included in the sample. In each school all eligible children are Mantoux tested. The number of children tested per district should be approximately constant. Increasing the number of selected districts is usually more efficient for increasing the precision of the estimate than increasing the number of children per district beyond several hundred to a few thousand.

Transmission of tuberculosis between people of different ages in The Netherlands: an analysis using DNA fingerprinting.

SETTING: In the period 1950 to 1980 the risk of tuberculous infection in the Netherlands declined more steeply than tuberculosis incidence. This study aimed at determining whether this might be explained by preferential transmission within age groups. METHODS: Using restriction fragment length polymorphism (RFLP) typing on all Mycobacterium tuberculosis isolates in the Netherlands from 1993 to 1996, clusters with identical fingerprints were identified. The correlation between the ages of people in clusters of two Dutch patients was determined. RESULTS: The mean difference in age between the two people, in 81 clusters of two, was 13.9 years, while the mean age difference between all possible pairs of individuals in this data set was 25.5 years. Fisher's intraclass correlation coefficient was 0.62 (95% confidence interval [CI] 0.46-0.74). CONCLUSION: It is concluded that sources of tuberculosis may preferentially transmit infection to people close to their own age. As the average age of cases has increased in the period 1950-1980, sources may have become less likely to infect children in whom the risk of infection has been measured. The annual risk of infection measured in children and young adults in countries with low levels of tuberculosis may not apply to older members of the population.

The point of view of a low prevalence country: The Netherlands.

The elimination of tuberculosis in the Netherlands is not envisaged before 2025. The evidence presented in this paper suggests that the elimination phase asks for a revision of existing control strategies. In the Netherlands a new role is identified for a voluntary tuberculosis organisation like the Royal Netherlands Tuberculosis Association (KNCV) in the areas of expert consultation, surveillance, post-graduate education and consensus and protocol development. A major challenge for a low prevalence country is the existence of high prevalence countries; KNCV's contribution to the success of the Mutual Assistance Programme of the IUATLD in Tanzania, Malawi, Benin, Kenya and Mali is discussed. A major role is identified for the IUATLD and voluntary organisations like KNCV in WHO's new global programme against tuberculosis. The involvement of a Dutch voluntary organisation, the Medical Committee The Netherlands-Vietnam (MCNV) in support of the national tuberculosis programme in Vietnam illustrates this development.

Tuberculosis and HIV-infection in developing countries.

Tuberculosis is a major public health problem in developing countries. In recent years, a (cost-)effective intervention has been developed in the national programmes of Tanzania and other developing countries. HIV transmission in populations with a high background prevalence of tuberculosis infection will increase the incidence of tuberculosis disease substantially. World Health Organization and World Bank are currently formulating new strategies to revitalise the global efforts against tuberculosis.

PIP: Tuberculosis (TB) has long been recognized as a complication of immune suppression. It poses a particularly major public health threat to developing countries. Many developing countries suffer high prevalence and incidence of TB infection. By suppressing host cell-mediated immunity, HIV exacerbates TB infection by helping to facilitate the transition of latent TB into active disease. Higher prevalence of active disease in population then leads to increasing rates of TB transmission. The World Bank estimates an annual incidence of greater than 7.1 million TB cases in the developing world. Cost-effective interventions have, however, been incorporated as components of national programs in Tanzania and other developing countries. The World Health Organization and World Bank are also working on new strategies to revitalize global efforts against tuberculosis. Finding TB cases early and treating them with chemotherapy are specifically recommended.