Studies on mode of detection of leprosy in China during the years 1981-1998.

Along with the nationwide economic reform initiated in the early 1980s and the rapid decrease of leprosy endemic after the implementation of multi-drug therapy (MDT), the leprosy programme changed from 'vertical' to 'horizontal'. An evolution in the mode of detection of leprosy cases has consequently taken place. Based on the nationwide registration of newly detected cases, the profile of patients at detection has been studied. The proportions of cases corrected significantly with calendar years in detection by dermatological clinics, contact checks, 'clue survey' and mass survey, showing a significant increase in percentage of cases detected through dermatological clinics and contact checks, and decreases through 'clue survey' and mass survey. Detection of cases through dermatological clinics and voluntary reporting have become the main modes of case-finding during 1997-1998, accounting for 37.3% and 28.6%, respectively, where contact check accounts for only 9.1%. In areas with good dermatological services, a significantly higher proportion (75.9%) of cases was detected through dermatological clinics, where voluntary reporting and 'clue survey' were the main modes of detection in endemic areas. As regards confirmation of diagnosis, the great majority of cases were confirmed by leprosy units, even though they were detected in various other situations. Only 6.5% of leprosy cases were detected and subsequently confirmed by doctors in dermatologic clinics. The present modes of detection and their relation to demographical, epidemiological, clinical factors and health services are discussed. This study emphasizes the cardinal importance of the dermatological clinics in the detection of leprosy cases in China at the present time and hence the need to strengthen the training of doctors in these clinics, while continuously encourage their involvement in leprosy control.

Leprosy in China: epidemiological trends between 1949 and 1998.

OBJECTIVE: To report the epidemiological trends of leprosy in China from 1949 to 1998. METHOD: Data for the study were obtained from the computerized database of the National System of Leprosy Surveillance. FINDINGS: A total of 474,774 leprosy patients were detected during this 50-year period. Case detection rates per 100,000 population were highest in the 1950s and 1960s, with peaks appearing in 1957-58, 1963-66, 1969-70, and 1983-84, corresponding to mass surveys or screening surveys carried out in most areas or selected areas of the country. While the duration of the disease at the time of detection fell over the period, the disability rates, which were > 50% in the early 1950s, have decreased gradually to 20.8% by 1997-98 but are still too high. More than 50% of cases were found through active methods in the periods 1955-58, 1965-66, and 1969-76, but in recent years cases are mostly detected through dermatological clinics or by voluntary reporting. The peak prevalences of the 1960s (i.e. > 2 per 10,000 population) decreased annually from the 1970s onwards. By the end of 1998 the prevalence was 0.05 per 10,000 population. CONCLUSIONS: This study shows that leprosy was well controlled in China and that the WHO goal of elimination of leprosy as a public health problem has been achieved at the national and subnational levels. However, leprosy is still unevenly distributed in the country. According to the criterion for leprosy elimination in China--defined as a prevalence of < 1 per 100,000 in county or city--there are still more than 10% of counties or cities where this target has not yet been reached. Special attention must therefore be given to achieve elimination and final eradication of leprosy in China.

Leprosy in children: a retrospective study in China, 1986-1997.

Leprosy in children forms an important link in the natural evolution and the epidemic profile of the disease. The study was undertaken on 1208 child cases detected during the years 1986-1997 in China. The number of child cases constituted 3-4 per cent of the total during this period although the incidence rates decreased dramatically. The detection rate significantly increased with age, and the average rate of 0.027 per 100,000 population was much lower than that in adults. In the pediatric cases, children in the younger age group had a higher prevalence of solitary lesions and lower prevalence of reactions and disabilities than the older group. A total of 70.01 per cent of the affected cases were infected by intra-familial contact, 35.60 per cent were detected by contact examination, and another 22.86 per cent by active surveys. The results of the study suggest that leprosy in children is not a public health problem at the present in China, but the regular screening of children in the family of patients is still one of the important ways to detect child cases and should be recommended.

Leprosy in China: delay in the detection of cases.

In a national survey in China, 27,928 cases of leprosy detected by the health authorities between 1984 and 1998 were investigated. The delay between onset of symptoms (estimated from each case's recall) and confirmed diagnosis was < or = 2 years for 55.1% of the new patients but > 10 years for 7.0%, with a median value, overall, of 22.0 months. The median delay was longer: (1) for the multibacillary cases than the paucibacillary; (2) among farmers than among factory workers; (3) among some nationalities than among others (being longest among the Tu and shortest among the Wei); and (4) for some methods of case-detection than for others. Over the study period, the mean delay decreased with time. The delay was greatest in the areas where leprosy was endemic and/or where access to health services was poor. The later the cases were detected the more likely they were to show disability. Leprosy cases are still going undetected in China, although, over the last 14 years, case-finding has significantly improved. Age, occupation, nationality, leprosy type and detection method all appear to affect the delay.

Prediction of elimination of leprosy in leprosy endemic areas of China.

A study was carried out based upon the data from the National System for Leprosy Surveillance and using appropriate mathematical models. The results showed that of 337 counties where the national goal of basic eradication of leprosy had not been reached and in 40 counties where the WHO goal of leprosy elimination had not been achieved in 1996, the detection rates in calendar years followed exponential models with significant goodness-of-fit. In the 67 counties with downward trends of detection rates, the national goal can be met in terms of detection rate in 6% of counties before the year 2000 or 34.4% before the year 2010, or, in terms of prevalence rate in 31.3% before the year 2010. In the 11 counties with downward trends of the detection rates, the WHO target can be met in eight to ten counties within this century when the duration of disease was determined with the WHO definition. If the MB proportion among new cases increased by 10%, the target would be met one year later. However, at the same MB proportion, the change of fixed treatment schedules from PB six months and MB two years to PB nine months and MB three years will cause achievement of the goal to be postponed by two to ten years.

Studies on risk of leprosy relapses in China: relapses after treatment with dapsone monotherapy.

Based upon the data from the Chinese National System for Leprosy Surveillance, this paper reports on the relapses in 297,343 leprosy patients [multibacillary (MB) 106,518, paucibacillary (PB) 190,825] cured by dapsone monotherapy. A total of 11,055 (MB 8675, PB 2380) patients relapsed during an accumulated follow-up period of 4,229,050 patient-years (PY), giving an overall relapse rate of 3.72 per 100 cases or 2.61 per 1000 PY, i.e., 8.14% or 5.91 per 1000 PY over an average follow-up period of 13.8 +/- 8.4 years in MB patients and 1.25% or 0.86 per 1000 PY over an average period of 14.5 +/- 8.9 years in PB patients. For either the overall relapse rate per 100 cases or per 1000 PY, the differences between MB and PB patients were statistically significant, except during 36-40 years of follow up. For both MB and PB patients, the relapse rates showed consistently significant decreases year by year, particularly in PB patients whose relapse rate per 1000 PY was 1.21 in year 10 of follow up; whereas it remained more than 10 per 1000 PY in MB patients. In view of that, the overall relapse rates in MB and PB patients cured by dapsone monotherapy were acceptably low, and most of these patients have been followed up for more than a mean incubation period of observed dapsone relapse. Along with the further extension of follow up, the risk of relapse in dapsone-cured patients will not be expected to increase. This conclusion should be considered when planning policy for the management of patients released from dapsone monotherapy.

Studies on risk of leprosy relapses in China: relapses after treatment with multidrug therapy.

Based upon the data from the Chinese National System for Leprosy Surveillance, this paper reports on the relapses in 47,276 leprosy patients cured by or released from WHO-recommended multidrug therapy (WHO/MDT). The overall relapse rate was 0.73/1000 patient-years (PY). There was a statistically significant difference in the relapse rates of WHO/MDT-MB (0.61/1000 PY) and WHO/MDT-PB (1.04/1000 PY) (chi 2 = 15.7, p < 0.01) patients. For multibacillary (MB) patients, the relapse rate in patients treated with fixed-duration MDT (0.56/1000 PY) was comparable with that in patients treated with MDT until skin-smear negativity (0.73/1000 PY) (chi 2 = 2.20, p > 0.05). Our present study suggests that fixed-duration MDT is a cost-effective regimen for the treatment of leprosy in China. The present results also show that relapse of leprosy is acceptably low and has not yet become a serious clinical or public health problem but, based upon the incubation of relapse in MDT patients, it is necessary to encourage annual follow up for at least 5 years for paucibacillary (PB) and 10 years for MB patients after being released from WHO/MDT.

An investigation of attitudes, beliefs and behaviour of leprosy patients, family members and PHC workers towards multidrug therapy in Yangzhou and Dongtai Districts of China.

To improve the operational efficiency of multidrug therapy (MDT) implementation in rural areas, an investigation into the attitudes, beliefs and behaviour of leprosy patients and their family members as well as primary health care (PHC) workers towards MDT was carried out in Yangzhou and Dongtai Districts of China. A sample of 370 leprosy patients, 594 family members and 730 PHC workers was interviewed or investigated individually using questionnaires. The results showed that: 1, the presently used MDT is acceptable to a wide range of patients although a small number of patients have various problems in their treatment; 2, the patients' habit in daily drug administration, their awareness of the risk of default and confidence in MDT have a positive influence in increasing drug compliance; and 3, the supervision and encouragement of family members to patients' treatment which is associated with their knowledge on MDT is also beneficial to patients' drug compliance. However, only half of the PHC workers had a basic knowledge of MDT and a desire to participate in MDT implementation, a finding which clearly calls for urgent attention and improvement. In order to ensure the effective implementation of MDT, there is a need to educate leprosy patients and their family members as well as PHC workers to establish the patients' correct awareness of MDT, obtain the family support and motivate the PHC workers.

The susceptibility testing of 13 strains of Mycobacterium leprae to rifampicin and the determination of minimal effective dosage.

By use of the mouse footpad technique, the susceptibility testing of 13 strains of Mycobacterium leprae to rifampicin (RFP) and the determination of minimal effective dosage (MED) were carried out. Among these strains of M. leprae, 8 were obtained from previously untreated multibacillary leprosy patients and 5 from relapsed leprosy patients without using RFP previously. The results showed that the MED of all strains to RFP were less than or equal to 0.001% FRP in the diet, 5 strains being equal to 0.001%, 5 less than or equal to 0.0001%, 2 greater than or equal to 0.0003% and 1 less than or equal to 0.0003%. The results indicated that the MED value of RFP could be lower than that of other reports. Because the critical concentration of RFP for assessment of RFP-resistant strains is not well established a further study would be worthwhile. The results of the determination of sera RFP concentrations in mice administered the RFP diet were identical with that of Holmes' report. Five of the 13 strains also showed that the growth of bacilli were suppressed by 10 mg/kg RFP using the gavage method.

Rapid serodiagnosis for leprosy--a preliminary study on latex agglutination test.

In this study, we have developed two latex agglutination tests (LATs) with phenolic glycolipid-I (PGL-I) and natural disaccharide-octyl-bovine serum albumin (ND-O-BSA) as antigens in 110 leprosy patients (LL = 30, BL = 30, BT = 30, and TT = 20), 50 tuberculosis cases, and 30 normal controls. These two LATs were compared with corresponding ELISAs (ND-O-BSA ELISA and PGL-I ELISA) and analyzed by the chi-squared test. There were no significant differences between the two LATs (PGL-I LAT and ND-O-BSA LAT) and their corresponding ELISAs. There was an increase in the proportion of positive cases detectable which coincided with the clinical classification of leprosy, i.e., lepromatous cases were more likely to be positive than tuberculoid cases. LATs are more simple and rapid than ELISAs and have high sensitivity (77% in ND-O-BSA LAT, 80.5% in PGL-I LAT) and specificity (99% in both LATs). LATs may become useful tools for the immunodiagnosis of leprosy in the field. The stability and repeatability of LATs are discussed in detail.

Evaluation of fluorescent leprosy antibody absorption test versus enzyme-linked immunosorbent assay with phenolic glycolipid 1 and their use in immuno-epidemiological studies on leprosy.

We systematically conducted comparative studies on the validity, reliability and practicality of FLA-ABS.T/PGI-ELISA in large samples. Namely, 284 leprosy patients, 20 tuberculosis patients, 172 normal controls (from nonendemic area of leprosy), 425 leprosy household contacts (HC) and 2573 random samples from the general population (RS) were involved. The results indicated that FLA-ABS.T/PGI-ELISA are highly sensitive and specific for detecting antibodies against M. leprae. Their Youden's indexes (YI) are greater than 90%, and the positive predicative and negative values are 90%. The test results agreed with immuno-epidemiological studies: 1. The positive rates using FLA-ABS.T/PGI-ELISA increased gradually from TT to LL leprosy patients (in HC, the positive rates of PGI-ELISA were much higher in contacts of multibacillary patients than in contacts of paucibacillary patients); 2. The positive rates detected by FLA-ABS.T were identical to those of PGI-ELISA both in HC and in RS; 3. Among RS, the positive rates detected by FLA-ABS. T/PGI-ELISA were similar in each district and were in concordance with the general prevalence rates. Thus, both FLA-ABS.T and PGI-ELISA are useful tests in diagnosing leprosy and detecting subclinical infection with M. leprae. However, because the PGI-ELISA is simple, it will be more practical than FLA-ABS.T in the future. The authors emphasize that the methodology of obtaining dried blood from ear lobes is important for the immuno-epidemiological study of leprosy on a large scale.

Studies on social medicine and leprosy in east China.

Leprosy is a disease in which the social, economic, cultural and environmental factors play an important role in occurrence, spread, control, eradication and rehabilitation. Eliminating the unfavourable factors hindering leprosy control can make achieving the goal of basic eradication of leprosy in China before the end of this century possible. For this reason, since 1984 we have carried out systematic studies of the social aspects of leprosy in Baoying County, a former high-endemic area in Jiangsu Province of East China, where the endemicity of leprosy is nearing full control.

Serological activity of natural disaccharide octyl bovine serum albumin (ND-O-BSA) in sera from patients with leprosy, tuberculosis, and normal controls.

We studied the natural disaccharide-octyl-bovine serum albumin (ND-O-BSA) enzyme-linked immunosorbent assay (ELISA) in sera from 151 leprosy patients, 20 tuberculosis patients, and 42 normal persons from a nonendemic area. The three ELISAs, whole Mycobacterium leprae (WML), phenolic glycolipid-I (PGL-I), and ND-O-BSA, are all highly sensitive for detecting antibodies against M. leprae. The results indicate that the serological activity has highly significant, positive correlations among the three types of antigens used. Their positivity rates are 100% with PGL-I and 97.4% with WML and ND-O-BSA in leprosy patients, and 0% with any antigen used in normal persons at NV-a (a supposed theoretical normal value). However, all three antigens show crossreactivity with tuberculosis patients at different levels. At NV-c (a supposed practical normal value, PNV), this crossreaction significantly decreased in the WML ELISA (PNV = 0.28) and the PGL-I ELISA (PNV = 0.16), and disappeared in the ND-O-BSA ELISA (PNV = 0.20). Under the same conditions, the positivity rates did not decrease significantly in leprosy patients, especially in multibacillary patients. Therefore, we suggest that the PGL-I ELISA in combination with the ND-O-BSA ELISA may be very useful for clinical applications, serodiagnosis, and for the study of subclinical infection in leprosy.

Determination of antibodies in dried blood from earlobes of leprosy patients by enzyme-linked immunosorbent assay--a preliminary report.

An enzyme-linked immunosorbent assay (ELISA) was used with soluble antigens of Mycobacterium leprae. All blood samples collected from the earlobes of 109 leprosy patients and 100 healthy controls (from a non-endemic area of leprosy) were absorbed with M. vaccae, BCG, cardiolipin, and lecithin according to the technology of the FLA-ABS test before being tested in the ELISA. The results (at a 1:200 blood dilution) showed that antibody activity gradually increased from TT to LL (mean OD values: TT = 0.43, BT = 0.62, BB = 0.72, BL = 0.84, LL = 0.89), and the rates of positive reactions were 100% in all classifications of patients except TT (66.6%). Antibody activity in the controls was less pronounced than in leprosy patients, their mean OD value being only 0.15. We suggest that the ELISA is highly sensitive and specific for the determination of anti-M. leprae antibodies, and is useful for clinical serodiagnosis and for the study of subclinical infections in leprosy.