[Estimation of the incidence of tuberculosis in The Netherlands in 2030]. / Projectie van het aantal tuberculosepatiënten in Nederland in 2030.

OBJECTIVE: To estimate the number of cases of tuberculosis (TB) in 2030 for the purpose of planning future TB control. DESIGN: Statistical modelling in 5-year intervals until 2030. METHOD: The number of Dutch TB cases infected by a Dutch source was estimated using a survival model. The number ofnon-Dutch patients was estimated by calculating the proportion of culture-positive TB patients among first-generation immigrants in 2005 and applying this proportion to the projected size of the non-Dutch population. It was assumed that each non-Dutch TB patient infected by a non-Dutch source would cause one infection in the population in The Netherlands. RESULTS: The estimated number of TB cases is expected to decrease to 877 in 2010. Only a limited decrease in the number of TB patients is expected after 2010 as the number of non-Dutch TB cases increases due to increased immigration. This increase negates the expected decrease in Dutch TB patients infected by a Dutch source. In 2030, non-Dutch TB cases will account for 85% of all TB cases. The proportion of non-Dutch TB cases is greater in the 4 largest cities, i.e. Amsterdam, Rotterdam, The Hague and Utrecht (89%) than in the rest of The Netherlands (76%). CONCLUSION: The decrease in TB incidence observed over the past several years may cease by 2010 due to an increase in non-Dutch TB patients as a result of increased immigration. However, the confidence intervals associated with these estimates were large. Future TB control efforts must be organised in a flexible way so that they can be adapted to changing epidemiological situations.

HIV-related mortality among tuberculosis patients in The Netherlands, 1993-2001.

Human immunodeficiency virus (HIV) infection in tuberculosis (TB) patients in The Netherlands during the period 1993-2001 was associated with an increased risk of death (adjusted odds ratio 4.71, P < 0.002). Age and sex-standardised mortality rates among HIV-infected TB patients decreased significantly over time, from 22.9% in 1993-1995 to 11.8% in 1999-2001 (P < 0.001). No such change was observed for HIV-negative patients. The decrease in mortality is likely due to the more widespread use of highly active antiretroviral therapy (HAART).

[HIV-test policy for tuberculosis patients in the Netherlands]. / Hiv-testbeleid bij tuberculosepatiënten in Nederland.

OBJECTIVE: To compare the proportion of tuberculosis patients tested for HIV infection, before and after introduction of highly active antiretroviral therapy (HAART) in the Netherlands, and to analyse predictive factors for performing an HTV-test in this population. DESIGN: Retrospective. METHOD: Whether patients had been tested for HIV, was investigated in random samples consisting of 200 patients, who were registered in the Netherlands Tuberculosis Register (NTR) in the years 1995 and 2001 respectively. RESULTS: The number of patients tested for HIV was 29 out of 84 (16%) in 1995, and 39 out of 190 (21%) in 2001 (not significant). HIV-tests had been carried out most frequently among homeless patients (71%), drug addicts (56%) and alcohol-abusing patients (60%). Significant predictive factors for HIV testing were place of residence (city), localisation of disease (pulmonary tuberculosis in combination with extrapulmonary tuberculosis) and place of origin (sub-Saharan Africa). CONCLUSION: Despite introduction of HAART during this period, in the Netherlands the proportion of tuberculosis patients tested for HIV did not significantly increase between 1995 and 2001. HIV testing was mainly limited to tuberculosis patients from risk groups.

HIV prevalence among tuberculosis patients in The Netherlands, 1993-2001: trends and risk factors.

OBJECTIVES: To describe the prevalence and predictive factors of human immunodeficiency virus (HIV) infection among tuberculosis (TB) patients in The Netherlands during the period 1993-2001. DESIGN: Data were obtained from the national surveillance register of all patients notified with TB (all forms) during the period of the study. In addition, records or discharge notes were checked of a random sample of 200 TB patients notified in 1995 and another 200 in 2001. RESULTS: Of 13 269 patients diagnosed with TB, 542 were HIV-positive (4.1%). Prevalence was 4.1% in 1993-1995, 3.8% in 1996-1998 and 4.4% in 1999-2001. The highest prevalence was observed among drug users (29.2%), homeless patients (20.1%) and patients residing illegally in the country (9.1%). Compared with the period 1993-1995, the relative risk of HIV infection in the periods 1996-1998 and 1999-2001 decreased significantly for drug using patients (P = 0.006), and increased for patients from African countries (P < 0.001). According to patient records, 29/184 (16%) had been tested for HIV in 1995 and 39/190 (21%) in 2001 (P = 0.289); 18 patients tested positive (4.8%). CONCLUSION: Although the prevalence of HIV among TB patients in The Netherlands remained stable between 1993 and 2001, the distribution of risk groups changed over this period.

Tuberculosis contact investigation and DNA fingerprint surveillance in The Netherlands: 6 years' experience with nation-wide cluster feedback and cluster monitoring.

SETTING: The Netherlands, 1995-2000. OBJECTIVES: To describe the contribution of 6 years of nationwide DNA fingerprint surveillance to tuberculosis control in general and to conventional contact investigations in particular. DESIGN: All Mycobacterium tuberculosis cultures are subjected to standardised IS6110-based RFLP typing, and clustered cases are systematically reported to the regional TB services involved (cluster feedback). Standardised questionnaires are used to collect information on contact investigations and epidemiological links (epi links) at regional level. Revision of the questionnaires for the period 1997-2000 allows comparison of epi linking before and after cluster feedback. RESULTS: Among 2206 clustered cases, 462 (21%) epi links were expected before the RFLP result, whereas an additional 540 (24%) epi links were established after cluster feedback. Epi links based on documented exposure increased by 35%, from 357 to 550 (P < 0.001). Only 1% of contact investigations were extended, however, and relatively few additional persons with active or latent tuberculosis were diagnosed. Reasons for the limited impact on contact investigation outcome were 1) contact took place 1-7 years previously (51%), 2) documented contact involved a subsequent case in the cluster (21%), 3) casual contact (15.5%) and 4) different region (9%). Five per cent of epi links established by contact investigation were contradicted by RFLP data. Epi links were more frequently documented in Dutch (41%) than non-Dutch cases (19%, OR 3.0; 95%CI 1.41-1.91). Cluster monitoring permitted: 1) identification of transmission chains that could not be detected by contact investigations, 2) development and evaluation of targeted interventions, and 3) identification of professional failures and poor programme performance. CONCLUSIONS: RFLP surveillance forms the bridge between conventional contact investigation and other forms of targeted active case finding. Combining both complementary strategies in a comprehensive approach to systematic outbreak monitoring and management allows countries in the elimination phase of the disease to better target and evaluate TB control interventions.

Pyrazinamide use as a method of estimating under-reporting of tuberculosis.

OBJECTIVE: To develop a method of validating the notification of active tuberculosis by physicians in the Netherlands. METHOD: The chemotherapeutic agent pyrazinamide was used as a marker for the occurrence of tuberculosis. On the basis of defined daily doses (DDD) of pyrazinamide dispensed to out-patients, an estimate was made of the number of patients with tuberculosis in the Netherlands in the period 1994-1998. DDD is a technical unit of measurement and does not necessarily reflect the recommended or actual dose used. Usually it is based on the average dosage per day for the main indication in adults with normal organ function. The Dutch Drug Information Project (GIP) of the Health Care Insurance Board (CVZ) provided the DDD data. Based on the notification of tuberculosis patients to the Netherlands Tuberculosis Register (NTR) we calculated how much pyrazinamide (measured in DDDs) these patients would have used depending on their body weight. RESULTS: The number of DDDs prescribed according to the GIP pharmacy records differed by only 8% from the number of DDDs calculated on the basis of notification to the NTR; 6889 patients should have been registered instead of 6349. CONCLUSION: The close correlation between the use of pyrazinamide as measured by the GIP and NTR provides strong evidence that in the Netherlands tuberculosis is reported in conformity with the guidelines for notifiable diseases. The method was simple to apply and may deserve follow-up in other countries.

Density of tuberculin skin reaction and its association with tuberculosis infection as defined by dual tuberculin testing.

OBJECTIVE: To determine whether the density of tuberculin skin reactions is associated with tuberculosis infection. METHODS: In a national tuberculin survey in Tanzania, 1983-1987, all eligible children in a random sub-sample of schools underwent dual tuberculin skin testing with PPD-RT23 and PPD-scrofulaceum. The density of reactions to RT23 was classified as proposed by Palmer. A larger reaction to PPD-scrofulaceum than to PPD-RT23 is suggestive of infection with environmental mycobacteria. Tuberculosis infection was defined based on dual skin test results applying a range of possible definitions. RESULTS: A total of 10,782 children aged 5-14 years and without BCG scar were included in the analysis. Large skin reactions to RT23 were generally firmer than small ones. After taking the size of the skin reaction to RT23 into account, its density was not associated with the size of the skin reaction against PPD-scrofulaceum. In particular, the density of reactions in the range 6-11 mm was not associated with tuberculosis infection according to any of the definitions used. CONCLUSION: This study suggests that the density of reaction was not associated with tuberculosis infection in Tanzanian school children after taking the size of the induration into account.

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.

Tuberculosis and the HIV epidemic: increasing annual risk of tuberculous infection in Kenya, 1986-1996.

OBJECTIVES: The purpose of this study was to assess the impact of the increased incidence of tuberculosis (TB) due to HIV infection on the risk of TB infection in schoolchildren. METHODS: Tuberculin surveys were carried out in randomly selected primary schools in 12 districts in Kenya during 1986 through 1990 and 1994 through 1996. Districts were grouped according to the year in which TB notification rates started to increase. HIV prevalence in TB patients and changes in TB infection prevalence were compared between districts. RESULTS: Tuberculous infection prevalence rates increased strongly in districts where TB notification rates had increased before 1994 (odds ratio = 3.1, 95% confidence interval = 2.3, 4.1) but did not increase in districts where notification rates had increased more recently or not at all. HIV prevalence rates in TB patients were 50% in districts with an early increase in notification rates and 28% in the other study districts. CONCLUSIONS: Countries with an increasing prevalence of HIV infection will need additional resources for TB control, not only for current patients but also for the patients in additional cases arising from the increased risk of TB infection.

Mortality among tuberculosis patients in The Netherlands in the period 1993-1995.

This study aimed to estimate excess mortality among tuberculosis patients in The Netherlands and identify risk factors for tuberculosis-associated mortality. The national tuberculosis register provided data on patients diagnosed in the period 1993-1995. Excess mortality in tuberculosis cases, according to age and sex, was determined by comparison with national mortality rates. Risk factors were identified and adjustment for confounders was carried out using Cox's proportional hazard analysis. Of 4,340 patients alive at diagnosis, 258 died within 1 yr while on treatment. The Kaplan-Meier survival probability after 1 yr was 93%. Tuberculosis patients had a standardized mortality ratio of 8.3. Independent risk factors for mortality were: gender; age; presence of a malignancy or human immunodeficiency virus (HIV) infection; addiction to alcohol or drugs; localization of tuberculosis; and the type of medical officer having made the diagnosis. Of all deaths, 83% occurred in two risk groups comprising 21% of tuberculosis patients: those aged > or =65 yrs and those having HIV infection or a malignancy. Tuberculosis patients in The Netherlands are at a considerably increased risk of death. However, the prognosis is very good for those aged less than 65 yrs and without human immunodeficiency virus infection or a malignancy.