Childhood tuberculosis in Germany between 1985 and 1994: comparison of three selected patient groups.

SETTING: Clinical and epidemiologic features of childhood tuberculosis in Germany are unknown for recent years. The characteristics of patient groups may show typical differences, depending on the source of data. OBJECTIVE: To identify typical features of childhood tuberculosis in Germany, and to relate the characteristics of patient groups to the purpose of the reporting centres. DESIGN: Comparative, retrospective, descriptive analysis of clinical and notification records by standardized data sheet. Evaluation of cases of active tuberculosis in children recorded between 1985 and 1994 at three study centres. RESULTS: One clinical study centre was a referral centre for sick children with an unclear diagnosis, the second specialized in tuberculosis, and the third was a public health office. Almost two thirds (64%) of the 285 evaluated patients were four years of age and under. Between 73% and 96% of children suffered from pulmonary disease and 17% to 58% were culture positive (range between study centres). Source cases had been found for 23% to 52% of children, and the primary reason for clinical evaluation was a positive tuberculin test for between 12% and 57%. Foreign-born children showed characteristic differences. CONCLUSION: The characteristics of reported childhood tuberculosis differ depending on the reporting centre. A significant number of notified cases were probably wrongly diagnosed.

Childhood tuberculosis: an index measuring the ability to detect cases early.

SETTING: Tuberculosis control programmes are conventionally monitored using data from sputum smear positive adult patients. Good overall results may mask significant and avoidable shortcomings with tuberculosis control in children. OBJECTIVE: To develop a specific surveillance tool for child patients, using the ability to detect cases early as a parameter for the impact of control measures. DESIGN: A simple index of early detection was compiled with values ranging from 0 to 100. Three groups of tuberculous children diagnosed in Germany between 1985 and 1994 (n = 303), and five other groups from the literature, were used to make a preliminary assessment of the validity of the index. RESULTS: The index values of 10, 13 and 24 for the German groups correlate well with other analysed patient data and the different functions of the institutions where the patients were diagnosed. Comparable characteristics could be found when applying the index to published data of other cases, with values of between 12 and 74. CONCLUSION: The proposed index seems suitable for monitoring early detection of child cases. Unexpected trends can be disclosed or effects of changed programme activities assessed. Routine use of the index would help the health services focus their attention on problem areas and specific patient groups with extremely low or falling index values. Conclusions can be drawn regarding the overall impact of the control programme.

Efficacy and safety of rifabutin in the treatment of patients with newly diagnosed pulmonary tuberculosis.

The efficacy and safety of rifabutin (RBT) and rifampicin (RMP) were compared in 298 patients with newly diagnosed pulmonary tuberculosis. In the initial 8-wk phase, all patients received isoniazid 400 mg/d, ethambutol 1200 mg/d, and pyrazinamide 2 g/d and were randomly allocated to receive either RMP 600 mg/d or RBT 300 mg/d. In the 16-wk continuation phase, patients received intermittent treatment (twice weekly) with isoniazid 600 mg/d, ethambutol 2400 mg/d and either RMP 600 mg/d or RBT 300 mg/d. Two hundred twenty-five (RMP = 118; RBT = 107) patients completed the 24-wk treatment period (evaluable patient population). Bacteriologic conversion rates in the RMP and RBT groups were 87.7 versus 92.0% at Week 8, 99.1 versus 99.0% at Week 12, 93.5 versus 93.8% at Week 24, and 89.8 versus 95.3% at the last valid observation. The mean time to first bacteriologic conversion was 14.1 wk in the RMP group and 14.3 wk in the RBT group. None of these differences was significant. Adverse events were reported by four patients (five events) in the RMP group and six patients (six events) in the RBT group. Those events thought to be associated with RMP were increased SGOT and leucopenia and, with RBT, increased SGOT and thrombocytopenia. Two hundred four patients entered the follow-up phase, and, of these, 95 (RMP = 49; RBT = 46) completed the scheduled 24-mo period. The overall rate of relapse was 3.8% (4/106) for the RMP group and 5.1% (5/98) for the RBT group. These differences were not significant. All relapsed patients, except for two who could not be traced, were successfully retreated. We conclude that the efficacy and tolerability of RBT is equivalent to that of RMP in the treatment of newly diagnosed uncomplicated tuberculosis, and that RBT can be effectively administered in a part-daily, part-intermittent dosage schedule.

Prepacked kits for diagnosis and treatment of tuberculosis in former Yugoslavia.

SETTING: After the outbreak of armed conflicts in the republics of former Yugoslavia in 1991, basic health services deteriorated and shortages of essential medical supplies occurred. The World Health Organization (WHO) has taken part in emergency relief operations in the area since July 1992. There was a growing concern that poor living conditions and shortages of supplies could rapidly increase the tuberculosis problem. OBJECTIVE: To provide essential supplies, WHO included support of tuberculosis control in the emergency relief operations for former Yugoslavia. DESIGN: WHO designed a prepacked kit with anti-tuberculosis drugs and material for sputum smear examination for use in combination with policy recommendations and a treatment protocol. RESULTS: The initial distribution of the kits was completed by the end of April 1994. Medium term support from May 1994 onwards has included continued distribution of kits, together with assistance in adjusting tuberculosis control programmes according to the recommended WHO policy package. CONCLUSION: Support of tuberculosis control with essential supplies and strictly focusing on priority measures is proposed as the most adequate strategy, when dealing with a developed country dependent on humanitarian assistance.

Use of BCG in high prevalence areas for HIV.

Recommendations state that, where the risk of tuberculosis is high, BCG should be administered to infants as early in life as possible, even if the mother is known to be HIV-infected. BCG should be withheld from individuals with symptomatic HIV infections. However, continuing reports from sub-Saharan Africa and elsewhere of BCG complications in HIV-infected persons call for a re-assessment of current vaccination policies. For HIV-infected infants any benefit of BCG vaccination may be marginal because the prognosis is very poor. It is however not possible to exclude HIV-infected children from BCG vaccination at birth. HIV-uninfected infants born to HIV-infected mothers are at great risk of tuberculosis infection, which justifies routine vaccination. BCG rarely causes serious complications. Theoretically, persons with asymptomatic HIV infection may be at greater risk of complications from BCG vaccines, but available data are inconclusive in that respect. To vaccinate children with BCG at one year of age does not seem feasible and would increase the risk of tuberculosis especially for uninfected infants of HIV seropositive mothers. Available data seem to indicate that routine vaccination of newborns is indeed safe, even in areas with high prevalence of HIV infection.

Random variation in tuberculin sensitivity in schoolchildren. Serial skin testing before and after preventive treatment for tuberculosis.

Schoolchildren were Mantoux-tested with 2 TU freeze-dried PPD RT23, and the strong reactors with indurations of 14.0 mm or more were selected for treatment with one of three different fixed drug combinations containing isoniazid or with placebo for 2 to 6 months. The initial tuberculin test was repeated after 8, 14, and 27 months. Of the 8,934 black schoolchildren initially tested, 5,165 did not react to the skin test, 2,898 had indurations up to 14.0 mm, and 871 reacted strongly. Of these strong reactors, 808 were allocated to four preventive treatment groups. On completion of treatment, the mean tuberculin reaction for all groups was significantly decreased. Because the placebo group showed changes similar to those seen in the other treatment groups, the tuberculin skin test is probably not suitable for monitoring the success of preventive therapy. Differences between skin test results before and after treatment when retesting only strong reactors are caused by a combination of effects that are difficult to distinguish. Assuming random variation in tuberculin sensitivity, the decrease can be explained as a combined effect of regression to the mean and some boosting. The increased reaction sizes in the subsequent Mantoux tests are explained by the booster phenomenon and possibly by reinfection. When using a cutting point for deriving a positive reactor, the chance of being selected for preventive treatment may depend primarily on the moment in time when the test is done. Thus, all reactors with no recent BCG vaccination should equally be considered for treatment.

Importance of rifampicin in combined daily/intermittent chemotherapy for tuberculosis.

Three different partly intermittent regimens were evaluated in order to assess the value of rifampicin (RMP) in the continuation phase of treatment for tuberculosis. Patients suffering from newly diagnosed culture-positive pulmonary tuberculosis were admitted to the trial. All were initially treated daily for 8 weeks with a quadruple combination including RMP. The intensive treatment phase was followed by twice-weekly intermittent treatment for 16 weeks with one of three different combinations, one containing RMP. Of 246 patients, 85 were withdrawn, 7 because of adverse events. At the end of treatment 127 of 135 patients (94,1%) from whom sputum results could be obtained, had negative sputum cultures, and 6 had one colony growth. Of 42 patients who had one or more positive sputum cultures during follow-up of 96 weeks, 6 belonged to the RMP group compared with 20 and 16 of the other groups (P = 0,0244). The results indicate that a combined daily/intermittent regimen containing RMP in both phases can be safely used, whereas a similar regimen with the same duration but not including RMP in the continuation phase, is inferior.

The need for co-operative operational research in tuberculosis control.

Progress in tuberculosis research and control is limited. Present control measures have seldom proved as successful as expected. Most of the problems encountered when implementing tuberculosis programmes are managerial and not technical. The only conceivable way to increase the impact of control measures is more effective application of conventional techniques. The data available seldom allow assessment, comparison and systematic improvement in the quality of control programmes. Similarly, the effectiveness of different techniques under specific conditions is difficult to assess. If the deficiencies in tuberculosis control schemes are to be overcome, research needs to be supplemented by co-operative operational research programmes. The aims of these programmes should always be to provide generally applicable guidelines and models for appropriate tuberculosis control schemes on a district level.