[The Dutch contribution to worldwide tuberculosis control: Royal Netherlands Association for the Prevention of Tuberculosis (KNCV) Tuberculosis Foundation]. / De Nederlandse bijdrage aan de wereldwijde tuberculosebestrijding: Koninklijke Nederlandse Centrale Vereniging tot bestrijding der Tuberculose (KNCV) Tuberculosefonds.

During the 1960s and 1970s tuberculosis was severely neglected in developing countries. Less than 50% of patients diagnosed were cured. However, an international breakthrough occurred in the 1980s with the excellent results from a short-course treatment: 80% cured. This was first achieved in Tanzania. Since 1993, this innovative approach has been known throughout the world as the 'directly observed treatment, short-course' (DOTS) strategy. Over the past 15 years the interest in international tuberculosis control has substantially improved. There has been a strong increase in the number of initiatives to rapidly extend the use of DOTS so that internationally set targets for tuberculosis control can be met (by 2005, 70% of infectious patients detected and 85% of these cured). The highest priority has been given to the 22 countries with the highest incidence of tuberculosis. There has been a significant increase in the number of countries implementing DOTS. The average rate of cure using DOTS is 80%. Since the 1970s the Royal Netherlands Tuberculosis Association (Koninklijke Nederlandse Centrale Vereniging tot Bestrijding der Tuberculose (KNCV)) has been involved in many international initiatives, such as the Stop TB Partnership, and it has participated in the development and implementation of policies for tuberculosis and tuberculosis-HIV control. However, there are still causes for concern: the number of tuberculosis patients is increasing in particular due to the tuberculosis-HIV co-epidemic and it is estimated that only 1 in 4 infectious tuberculosis patients were detected and treated in DOTS programmes during the year 2000.

High tuberculosis notification and treatment success rates through community participation in central Sulawesi, Republic of Indonesia.

SETTING: Central Sulawesi Province, Republic of Indonesia. OBJECTIVE: To increase tuberculosis case notification and maintain high treatment success rates through community participation in a tuberculosis field programme. DESIGN: Comparison of tuberculosis case notification and treatment results in a community based tuberculosis programme (CBTP), before and after introduction of the programme and between areas where the programme was and was not introduced. RESULTS: During 1998, the CBTP was introduced in two of the four rural districts of the Central Sulawesi province, covering 224 (29%) of the 772 villages and 362,700 (33%) of the 1,109,100 population in these districts. In the CBTP villages the notification rate of new smear-positive patients per 100,000 population increased from SI in 1996 and 48 in 1997 to 166 in 1998. In the 548 non-CBTP villages the rates were 62, 60 and 70, respectively. The sputum conversion rate at the end of the first 2 months of the treatment was over 85% in both the CBTP and the non-CBTP villages. In the CBTP villages the treatment success rate (cure and treatment completion) was 90.4%, 89.5% and 93.7% in 1996, 1997, and 1998. For the non-CBTP villages these rates were respectively 85.4%, 86.8% and 85.9%. In 1998 the sputum conversion and treatment success rates were significantly higher in the CBTP villages than in the non-CBTP villages. CONCLUSION: Through community participation, the notification of new smear-smear positive patients increased substantially, while sputum conversion and treatment success rates remained high.

Short-course instead of long-course chemotherapy for smear-negative patients in sub-Saharan Africa.

The use of short-course chemotherapy (SCC) in directly-observed treatment, short-course (DOTS) programmes in sub-Saharan Africa was often restricted to patients with infectious and serious forms of tuberculosis, because of high costs of such regimens. With reduced drug prices and wide-scale substitution of thiacetazone by ethambutol in the continuation phase of treatment, various short-course regimens are now available at the same or even lower costs than long-course regimens. Several DOTS programmes are considering extending access to short-course chemotherapy to non-infectious patients, or have done so already. The authors provide an overview of the issues regarding the debate on the introduction of universal SCC in national tuberculosis control programmes in low-income countries in sub-Saharan Africa. They advise on a low-risk strategy to avoid the emergence of rifampicin resistance as a consequence of the wide availability of rifampicin associated with universal short-course, and strengthening of the health system to maintain high performance levels in diagnosis and treatment.

High cure rates in smear-positive tuberculosis patients using ambulatory treatment with once-weekly supervision during the intensive phase in Sulawesi, Republic of Indonesia.

SETTING: The four provinces of Sulawesi, Republic of Indonesia. OBJECTIVE: Treatment of smear-positive pulmonary tuberculosis patients using ambulatory treatment with supervision once weekly during the intensive phase and once fortnightly during the continuation phase. DESIGN: Pilot projects with gradual expansion of activities according to defined quantitative criteria. RESULTS: During the period January 1993-December 1997, 11,879 new smear-positive and 320 smear-positive previously treated patients, of whom 259 were relapses, were placed on short-course chemotherapy. At the end of the intensive phase, 87.5% of new patients and 80.0% of retreatment patients had become sputum smear-negative. During the period January 1993-December 1996, of 7,251 new smear-positive patients placed on treatment 85.2% were cured and an additional 7.9% had completed treatment, giving a total success rate of 93.1%. For 239 patients placed on retreatment the total success rate was 86.6%. CONCLUSION: The treatment results show that the policy introduced in Sulawesi is effective. In two provinces priority will now be given to increasing case detection, while in the other two provinces the emphasis will be on reaching full coverage. The reasons for the success of the projects are discussed, as are the prerequisites for introducing the policy in other areas.

Evaluation and planning in national tuberculosis control programmes: the usefulness of the standardised patient treatment card.

Through systematic evaluation of information contained in tuberculosis patients treatment cards, we present an example of a rapid operations evaluation method for identifying issues important to a national tuberculosis programme (NTP). Analysis of all 279 treatment cards of patients scheduled to attend one specific clinic day was made ((Kinondoni district in Dar es Salaam, Tanzania). Two hundred and twenty five patients (81%) were diagnosed as having pulmonary tuberculosis. Males accounted for 61% of cases. Ninety two per cent were cases without prior history of treatment. Of all patients, those under 15 years and those aged 25 to 54 years were more likely to be sputum smear-negative compared with other age groups. A chest radiograph was obtained as recommended to support the diagnosis in only 61 (38%) of 160 cases diagnosed as sputum smear-negative pulmonary tuberculosis. Initial drug dosing based on weight (mg/kg) revealed frequent dosing errors of isoniazid (97%) and pyrazinamide (65%), almost exclusively overdosing, in sputum smear-positive patients. Systematic examination of patient treatment cards provided usefull information and raises issues important to NTP planning and operations. Weaknesses in the execution of the national programme in Dar es Salaam were identified: the under-utilisation of chest radiography to diagnose sputum smear-negative tuberculosis and overdosing of certain drugs.

PIP: The tuberculosis (TB) patient treatment card proposed by the International Union Against Tuberculosis and Lung and Disease provides both patient and protocol-specific information. In addition to data on age and gender, the cards contain information on body weight, drug dosing, sputum smear microscopy results, and the use of chest radiography for diagnosis. All 279 treatment cards of patients scheduled to attend one specific TB clinic day in Kinondoni district, Dar es Salaam, Tanzania, were analyzed as an example of a rapid operations evaluation method for identifying issues important to a national tuberculosis program (NTP). 225 patients were diagnosed with pulmonary TB, of which males comprised 61%. 92% were cases with no prior history of treatment. Patients under age 15 years and those aged 25-54 were more likely than other age groups to be sputum smear-negative. A chest radiograph was obtained to support the diagnosis in 61 of 160 cases diagnosed as sputum smear-negative pulmonary TB. Initial drug dosing based upon patient's weight revealed frequent dosing errors of isoniazid and pyrazinamide in sputum smear-positive patients. Observed error was almost exclusively overdosing.

Eliminating leprosy as a public health problem--is the optimism justified?

Systematic use of multidrug therapy has proved to be so effective that leprosy can be eliminated as a public health problem by the end of the century. However, because of the long incubation period of this disease, together with the time-lag in case detection, the factors involved in achieving and sustaining its elimination have to be very carefully defined.

Relapses among leprosy patients treated with multidrug therapy: experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia; practical difficulties with diagnosing relapses; operational procedures and criteria for diagnosing relapses.

Multidrug therapy (MDT), according to the recommendations of a WHO Study Group of 1982, was introduced in the leprosy control program of the All African Leprosy and Rehabilitation Training Center (ALERT), Ethiopia, in January 1983. Paucibacillary (PB) patients are treated with 6 months of MDT. Multibacillary (MB) patients are treated with at least 2 years of MDT and until skin-smear negativity. An analysis was made of the relapses which had been diagnosed among self-reporting patients in four rural districts and Addis Ababa. Among 3065 PB patients, 34 relapses (1.1%) were diagnosed during an average period of 6.1 years after stopping MDT (range 2 1/2 to 7 1/2 years). Among 2379 MB patients, 24 relapses (1.0%) were diagnosed during an average period of 4.7 years after stopping MDT (range 2 1/2 to 6 years). The estimated relapse rate per 1000 patient-years after release from MDT was 2.1 for PB patients and 2.4 for MB patients. From the analysis of the clinical, bacteriological, and histopathological findings, it was concluded that there was strong positive evidence for the diagnosis for 16 of the 34 relapses in the PB patients and for 0 of the 24 relapses in the MB patients. The main cause for overdiagnosis of MB relapses was that too much reliance had been put on skin-smear results, without a careful comparison of the results with those from before, during, and at completion of MDT; the diagnosis was based on the finding of positive smears in one set of smears only; insufficient attention was given to finding solid-staining bacilli; and findings in biopsies, if these were examined, did not confirm the diagnosis. The main cause of overdiagnosis of PB relapses was that too much reliance was put on histological findings, while these are often inconclusive for differentiating between a relapse and late reversal reaction. Recommendations are made on how to limit overdiagnosis of relapses. Operational procedures and criteria for making the diagnosis under conditions where facilities for back-up histological and mouse foot pad investigations are not available are proposed.

Duration of multidrug therapy in paucibacillary leprosy patients; experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

Multidrug therapy (MDT), according to the recommendations of a WHO Study Group of 1982, was introduced in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT), Ethiopia, in January 1983. Of 6042 paucibacillary patients who were put on MDT during a period of 7 years, 5485 patients (90.8%) completed the course of MDT; 437 patients (7.2%) did not fulfill the requirement for clinic attendance and either discontinued MDT themselves or the treatment was discontinued by the service. The remaining 120 patients (2.0%) either died, were transferred, left the control area or continued MDT after 9 months. The urine spot test for the presence of dapsone showed a significantly higher proportion of positive results for patients on MDT than for patients on dapsone. The analysis of the compliance with the prescribed doses of MDT showed that of 963 patients, 81.9% received six doses of MDT and 18.1%, more than six doses; 82.6% of these 963 patients attended with 100% regularity, 12.7%, 3.6%, and 1.1% missed one, two, or three clinic appointments, respectively, while fulfilling the requirement for overall clinic attendance. Of the 429 patients who had not been treated with dapsone before MDT, the skin lesions were clinically active at the time of stopping MDT in 130 patients (30.3%). In all, except one of the 114 patients (0.9%) who attended for follow-up examinations, the skin lesions had become clinically inactive within 2 years after stopping MDT. The recommended duration of MDT is discussed based on findings in the ALERT leprosy control programs and observations by others.

Relapses in leprosy patients after release from dapsone monotherapy; experience in the leprosy control program of the all Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

Before implementation of multidrug therapy (MDT), leprosy patients who were clinically inactive, skin-smear negative and had been treated with dapsone monotherapy for at least 5 years (paucibacillary patients) or for at least 10 years (multibacillary patients) were released from treatment. An analysis was made of self-reporting relapses in 1081 paucibacillary (PB) patients and 1123 multibacillary (MB) patients who had been released in Addis Ababa and two rural districts of the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT). During an average period of 6.6 years after stopping dapsone, 44 relapses were diagnosed among the PB patients and 148 relapses among the MB patients. The overall relapse rate was 4.1% or 7.2 per 1000 patient-years after release from treatment for PB patients and 13.2% and 24.8, respectively, for MB patients. The annual relapse rate in PB patients did not differ significantly from year to year. However the relapse rate for MB patients was significantly lower during the fifth to seventh years after stopping treatment compared with the first 4 years. Based on clinical findings there was a strong suspicion of relapse with dapsone-resistant bacilli in 40.4% of MB relapses. It is concluded that the relapse rate for PB patients is acceptable. However, the relapse rate for MB patients is considered too high. It is strongly recommended to administer to all MB patients, including those who have been on long-term treatment with dapsone and have become clinically and bacteriologically inactive, a 2-year course of MDT.

Occurrence of reactions, their diagnosis and management in leprosy patients treated with multidrug therapy; experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

This paper reports on reactions in leprosy patients who were treated with multidrug therapy (MDT) in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia. Only those reactions which occurred in patients who had not been treated with dapsone before MDT and which required treatment with prednisolone were included. Until the end of the second year of MDT a reversal reaction had been diagnosed in 43.6% of 266 borderline lepromatous (BL) patients and in 19.2% of 109 lepromatous leprosy (LL) patients, and an erythema nodosum leprosum (ENL) reaction in 2.7% and 11.1% of the patients, respectively. The reversal reactions were observed in 4.9% of the BL patients and in 0% of the LL patients at the time of diagnosis of leprosy, in 26.3% and 12.8% of the patients during the first year of MDT, and in 12.4% and 6.4% during the second year of MDT. ENL reactions were seen in 0.8% of BL patients at diagnosis, 1.1% in the first year and 0.8% in the second year and 2.8% at diagnosis, 5.5% in the first year, and 2.8% in the second year for LL patients. During a 3 1/2-year period, a total of 405 reactions were diagnosed among multibacillary (MB) patients on MDT; 365 of these reactions (90.1%) were reversal reactions and only 40 (9.9%) were ENL reactions. The point in time of the reversal reactions showed that the risk of reversal reaction is highest during the first year of MDT. Thereafter there is a gradual decline, although reactions were still observed during the fifth year of MDT. A reversal reaction was diagnosed in 21.0% of 438 BT patients; in 3.4% of the patients the reaction was present at the time of diagnosis of leprosy; in 10.3% it occurred during MDT, and in 7.3% during the first year after release from MDT. During a period of 3 1/2 years a total of 183 reversal reactions were diagnosed among BT patients. The point in time showed a declining trend in the risk of reversal reaction after starting MDT. The risk is highest during MDT, followed by the first 6 months after stopping MDT. However, reactions, although few, still occurred during the fourth year after stopping MDT. The analysis of the results of prednisolone treatment in 161 patients who were treated for nerve function loss in the field showed that 142 patients (88.2%) regained complete or partial recovery of the nerve function(s), while no improvement was observed in 19 patients (11.8%).(ABSTRACT TRUNCATED AT 400 WORDS)