Epidemiological information on leprosy in the Singu area of Upper Burma.

In the course of a WHO trial designed to evaluate the possible protective action of BCG vaccine against leprosy, a longitudinal epidemiological study of the whole population was carried out in an area of very high endemicity in Burma from 1964 to 1976. Two mass surveys of the whole population with an interval of 4 years and annual re-examination of the 28 000 children (0-14 years) in the BCG trial were carried out. The data collected yielded important information about general prevalence and yearly incidence of the disease as well as on sex, age, and classification of cases. The general prevalence rate declined from 32.6 per 1000 in the first survey to 25.2 per 1000 in the second. The number of cases among males was significantly higher than among females. Incidence rate among contacts of already known cases was 9.8 per 1000 person-years. The estimated yearly incidence among non-contacts was 5.9 per 1000. Prevalence rates reached a peak in the 20-39-year age group. The prevalence rate of multibacillary patients also reached a peak in the same age bracket. It is stressed that a further period of epidemiological surveillance will be essential in order to have a correct estimate of the expected number of new infections, especially multibacillary cases, in the 20-39-year group. The value of this information is considered unique for planning and programming of future control activities.

Proposed method for estimating leprosy prevalence based on rates in children.

The authors suggest that, where leprosy prevalence data for the entire population are lacking, the prevalence in schoolchildren may be a valuable index for estimating the magnitude of the problem in areas where leprosy is endemic.

Some epidemiological data on leprosy collected in a mass survey in Burma.

In the WHO Leprosy BCG Trial in Burma a mass survey was undertaken to determine whether children had been exposed to patients with leprosy and, if so, the form of the index case. This paper presents the most important epidemiological data collected in this survey. The prevalence rate was 31.6 per 1 000. It seems that even if the prevalence rate is very high the L rate does not increase accordingly. The high T rates in areas of high endemicity seem to be related mainly to the degree of spreading of leprosy, even to persons who react to lepromin. Comparison of the results with data available for the area before the survey was made shows that 87% of the L cases had already been detected and that 54% of the T cases had not. There was a tendency for high L rates to be associated with high prevalence rates. The results do not suggest that any particular age group has greater susceptibility or resistance; the prevalence rates seemed to be related mainly to the age when exposure occurred. A higher prevalence of leprosy in males started to appear in the 10-14-year age group, and after the age of 15 the difference became impressive. Biological, socio-economic, and environmental factors seem to be responsible for the level of endemicity, which does not seem to be essentially or primarily related to ethnic origin.

BCG vaccination of children against leprosy: seven-year findings of the controlled WHO trial in Burma.

A controlled study of the efficacy of BCG vaccination for the prevention of leprosy began in Burma at the end of August 1964. This paper presents the findings after 7 years-i.e., the results of 6 annual follow-up examinations up to the end of June 1971. The incidence rate in BCG-vaccinated children 0-4 years of age at intake was lower than that in children in the control group. The protection conferred by BCG was relatively low (44%) and applied only to early cases of leprosy, the great majority tuberculoid cases. BCG vaccination did not protect household contacts or children 5-14 years of age who were not exposed in the household. This reduction must be interpreted in the light of several factors: form of leprosy, bacterial status, lepromin reactivity, evolution of cases, and level of endemicity. Consequently it does not seem probable that the reduction in incidence would substantially affect the pattern or trend of the disease in an area similar to that where the study is being carried out; the probability would be much lower if not nil in regions of relatively low endemicity (1-2 per 1 000 or less).

WHO co-ordinated short-term double-blind trial with thalidomide in the treatment of acute lepra reactions in male lepromatous patients.

The treatment of lepra reactions constitutes one of the most serious problems in leprosy. For this reason, the first reports in 1965 of the favourable results obtained with thalidomide aroused considerable interest and led WHO, in 1967, to carry out a trial with the co-operation of four centres. A short-term double-blind trial was designed to study the effect of thalidomide, in comparison with acetylsalicylic acid, in the treatment of acute lepra reactions in male lepromatous patients. Acetylsalicylic acid was used instead of a placebo because of its antipyretic and analgesic activity. Because of the severe adverse reactions that may be caused by thalidomide, mainly the teratogenic effects, only males were included in the trial.The results of this short-term study seem to confirm previous reports of the efficacy of thalidomide and indicate that acetylsalicylic acid also seems to be helpful in the management of certain symptoms of lepra reactions.

BCG vaccination of children against leprosy. Preliminary findings of the WHO-controlled trial in Burma.

The use of BCG vaccine in the prevention of leprosy has been one of the most important subjects of investigation in the field of leprology in the last 25 years. The action of the vaccine was for many years investigated by determining its effect on the lepromin reaction. Field studies were later considered essential to determine whether BCG vaccination would be useful to leprosy contacts, to the child population probably exposed to infection, or to persons persistently lepromin-negative.The interest of the World Health Organization in this matter began in 1952 and, following the recommendations of certain advisory committees, it was decided to institute a field trial in Singu township in Burma. The main purpose of the investigation was to observe, in a highly endemic area, the protective effect, if any, of BCG vaccine against leprosy in the child population not exposed to Mycobacterium leprae at home but possibly exposed to the infection elsewhere.Field operations began at the end of August 1964 and the preliminary findings obtained up to the end of June 1968 relate to 3 annual re-examinations. So far, from the material studied, it appears that, under the conditions prevailing in Singu township, no significant effect of BCG vaccine can be seen within a period of 3 years. When children in both trial groups are followed-up for much longer periods, mainly children aged 0-4 years at intake, it is possible that a significant difference may emerge. However, to be operationally desirable, a merely significant difference is not enough; the protective effect of BCG should be substantial to warrant its large-scale use as an immunization procedure against leprosy.

Therapy of leprosy.

The latest developments and ideas in the therapy of leprosy are discussed, the need for long-term studies being stressed. The therapeutic efficacy and effective dosages of some sulfones (especially diaphenylsulfone), thiambutosine and long-acting sulfonamides such as sulfamethoxine and sulfalene, are considered. The possibilities for two newer drugs, 4,4'-diacetyldiaminodiphenylsulfone and clofazimine (B-663), both still in the early stages of evaluation, are also described and the potential value of thalidomide in treatment of the lepra reaction is discussed. The authors make a number of recommendations for controlled trials and lines of investigation and, in particular, favour a biochemical approach to the correction of defective host defences. Diaphenylsulfone is still considered the drug of choice for use in the therapy of leprosy.

Studies towards the standardization of lepromin. Progress and prospects.

Because of the wide range of concentrations of Mycobacterium leprae in existing lepromins the authors studied methods of producing a standardizable lepromin containing 160 million bacilli/ml. The effects of using different dilutions of lepromin on the incidence of false-positive reactions were also studied.Progress reported includes a convenient method for preparing large batches of non-sedimenting lepromin, which is directly suitable for microscopic counting of Myco. leprae cells; and a validation of current methods for microscopic enumeration of Myco. leprae. Skin tests with diluted lepromins have demonstrated that dilutions up to 1:16 increase progressively the ability to distinguish between lepromatous and tuberculoid leprosy. This work has provided further evidence that 20 million bacilli/ml (a 1:8 dilution of the initial lepromin) should produce adequate Mitsuda reactions in general populations, provided that 3-mm reactions are taken as the criterion for 1+ positivity. The net effect of these findings is equivalent to expanding the world supply of lepromin by 8 times.Recommendations for further research are proposed.