Studies on risk of leprosy relapses in China: Relapses after treatment with Dapsone monotherapy

International Journal of Leprosy and Other Mycobacterial Diseases, Dec 1999 by Chen, Xiang-Sheng, Li, Wen-Zhong, Jiang, Cheng, Ye, Gan-Yun

Studies on Risk of Leprosy Relapses in China: Relapses After Treatment with Dapsone Monotherapy1

The organized leprosy control program was launched in China in the mid-1950s. Dapsone (DDS) administration as monotherapy remained the mainstay of leprosy treatment until 1986 when the World Health Organization-recommended multidrug therapy (WHO/MDT) was introduced nationwide. However, many of the patients reaching clinical cure were still kept on maintenance therapy with regular or irregular dapsone 50-100 mg daily for 5-10 years for multibacillary (MB) patients and 2-5 years for paucibacillary (PB) patients, and even in some patients the treatment duration was life-long. Between 1949 and 1997, 472,771 leprosy patients were detected of whom approximately 80% had been treated with DDS monotherapy, 11% with MDT recommended by WHO, 3.3% with other regimens, mainly including various durations of dapsone plus rifampin, during 1979-1984 in some areas, and the remaining 5.7% of the patients had never received any formal treatment. Since 1949 a total of more than 310,000 patients have been treated with DDS monotherapy and declared as clinically cured. The patients treated with DDS were declared as clinically cured when they achieved clinical, bacteria] index and histopathological negativity. For the purpose of evaluating the long-term efficiency of DDS monotherapy and providing some light on the surveillance and management for the patients cured by DDS monotherapy, relapses among the patients who had been cured by DDS monotherapy and followed up for up to 40 years are reported as follows.

MATERIALS AND METHODS

This study is part of a large project covering the whole of China for the purpose of establishing a national system for the epidemiological study and surveillance of leprosy. Based upon this project, the National System for Leprosy Surveillance was initiated in 1989 by the Ministry of Public Health and established in the National Center for STD and Leprosy Control located in Nanjing. Excluding three nonendemic areas (Beijing, Inner Mongolia and Shanxi) as well as Taiwan Province and the Hong Kong Special Administrative Region, this system covers 27 provinces, municipalities or autonomous regions (PMRs) in China. The present study on the relapses of leprosy was made in these 27 PMRs.

Patients and follow up. The patients enrolled in the present study were those who had been treated with DDS monotherapy and declared as clinically cured with clinical, bacteriological and histological negativity, and then followed up for more than half a year, For most of these cured patients, the long-tenn follow up was passive, but at the county and even sub-county levels the network of leprosy control was so powerful that they can almost immediately update the changes (i.e., relapse, death, etc.) in these patients. In addition, a retrospective sifting for the data of all cured, dead and defaulted patients carried out nationide was collected with specialized forms by the local leprosy workers in 1990 and then sent to the National Center for STD and Leprosy Control after having been checked by the prefectural and provincial authorities. For the patients who were clinically cured by DDS before 1990 and still alive after 1990, the deadline for them to be excluded from the cohort of follow up was determined on the basis of the life expectancy of the population. A total of 297,343 leprosy cases cured by DDS monotherapy met the criteria of follow up for the present study and 11,055 relapse patients were used for the analysis.

Criteria of relapses. The diagnosis of relapse after DDS monotherapy was based on the criteria defined in Practical Leprology (4), i.e., a "case of relapse" is defined as a clinical and bacteriological reactivation of the disease in a person who has been declared as clinically cured through the strict clinical, bacteriological and pathological evaluations. The criteria were revised in the Handbook of Leprosy Control (8). The presence of one or more of the following features was considered as evidence for relapse: a) an insidious appearance of new lesions and/or reactivity of lesions that had previously disappeared; b) a reappearance of bacilli (fresh multiplication of surviving leprosy bacilli), i,e., positive reappearance of acid-fast bacilli (AFB) after skin-smear negativity; and c) the specific evidence of relapse and/or positive AFB in the histopathology of a suspected lesion. Operationally, the diagnosis of relapses mainly depends upon bacteriological examination in combination with clinical and histopathological examinations. Relapses after DDS monotherapy can be diagnosed and confirmed by leprosy workers at the district level.

Statistical analysis. The number of patients who relapsed during follow up was used as the numerator and the number of patients who reached clinical cure by DDS monotherapy and their total follow-up duration in terms of patient-years (PY) were used as the denominators for calculation of relapse rates per 100 patients or per 1000 PY. The period in years of follow up was defined as the duration between the calendar year of clinical cure and the year of the patient's exclusion from the cohort of follow up or the end of 1997. The incubation period was made as the duration from the declaration of clinical cure to the diagnosis of relapse. For statistical significance, the chi-squared (chi^sup 2^) test was used for comparison between the percentages or relapse rates. The mean periods of follow up or the mean incubation of relapses were compared using the Student's t test. All statistical tests were done by means of the STATA v.3.0 or Epi-Info 5.0 program. Differences were considered significant at the 95% level of confidence (p