Special considerations in the design, conduct and analysis of prophylaxis trials.

Methodological considerations in clinical trials apply to prophylaxis studies also. In addition, there are certain aspects that need special attention. These are the identification of a valid group of controls, the choice of the unit of randomization and its impact on subsequent analyses, the specificity and the sensitivity of case diagnosis and their impact on estimated efficacy and its reliability. The ethical aspects of the trial also need special consideration, bearing in mind that the intervention is on healthy individuals, and not patients with disease. These are discussed in the context of community prophylaxis trials of tuberculosis and leprosy undertaken in south India.

Some indices pertaining to the leprosy control programme in Tamil Nadu, based on data from a random sample of fourteen government control units.

From a random sample of 14 Government Leprosy Control Units in Tamil Nadu, information on the profile of the newly-diagnosed leprosy patients and some important aspects of the control programme in 1978-81 was collected when monotherapy with dapsone was the practice. Among the new patients, 55 per cent were males, 24 per cent were children, 6 per cent had lepromatous leprosy and 9 per cent had a deformity. About 65 per cent were detected by active case-finding methods and 25 per cent were voluntary referrals. Of the total diagnosed patients, only 68 per cent started treatment; further, of these, about 40 per cent collected drugs for at least 6 months in the first year of treatment. The average attendance at the clinic was 34 per cent of the due attendance. Coverage in the annual examination of family contacts was 57 per cent. During the 4 yr period, about 70 per cent of the villages had population surveys with a coverage of 75 per cent or more. The introduction of multi-drug therapy has provided a new impetus to the programme and therefore a similar study is called for to provide valuable information about the extent of improvement in completion rates and overall impact.

PIP: Researchers used 1978-1981 data from a random sample of 100 rural subcenters of 14 government leprosy control unites (LCUs) in Tamil Nadu, India to learn the status of indices of the National Leprosy Control Programme. The lepromatous rate stood at 6% (4-10% range) with males having a much higher percentage (8.6% vs. 3.9%) and children having a much lower percentage (.6% vs. 8.3%). It was highest for those who voluntarily reported their condition (10.4%) and lowest for those detected during a routine contact examination (2.5%). Active case finding techniques detected most new cases [65%; population survey (59%) and routine contact examination (6%)] followed by voluntary referrals (25%; 8-44% range) and miscellaneous sources. Only 68% (38-82%) of newly diagnosed cases started treatment in the same calendar year or the next. Indeed 46% of those detected by population survey and 37% of contact examination did not even register. Therefore the active case finding program does not bring full benefits to patients. It should undertake intense efforts to motivate all diagnosed patients to take treatment. Moreover, as many as 60% of patients did not collect the drugs needed for the multidrug therapy for =or + 6 months. Some of these did not even do so in the 1st year of treatment. As time passed, the levels of irregularity rose (65% in 2nd year and 71% in 3rd year). Perhaps LCU staff should use a group approach to motivate patients to collect the needed drugs rather than an individualizes approach. In addition, 18-89% of patients at time of registration had a bacteriological examination in 12 LCUs. The median stood at 69%. The percentage of patients who have a bacteriological examination must improve since the multidrug therapy regimen is dependent on the type of leprosy the patient has (multi or pauci bacillary leprosy).

Association between regularity in dapsone (DDS) treatment and development of deformity.

The existence of an association between regularity in dapsone intake and the development of deformity was investigated in 5746 leprosy patients under treatment in South India. The incidence of deformity, year by year over a 5-year period, increased significantly with increasing levels of drug collection. The excess incidence in "more regular" patients was significant at all ages and in both sexes in nonlepromatous (N) cases. The same was true in intermediate (N?L) cases except in patients under 15 years of age. The evidence in lepromatous (L) cases was not so consistent. Independent confirmation of the presence of the association was sought through a matched case-control type of analysis with 140 N, 48 N?L, and 81 L cases, matching being undertaken with respect to sex, age, type of leprosy, year of starting treatment, and observation period. This showed that the mean regularity in cases (deformed patients) before the development of deformity was significantly higher than the mean regularity in the corresponding matched controls, the differences being particularly large among the N and N?L types. These findings raise the possibility of a causal link between regular dapsone intake and the development of deformity.

A 20-year study of the Leprosy Control Programme at the Hemerijckx Leprosy Centre in Polambakkam in South India.

The Hemerijckx leprosy centre at Polambakkam in South India covers a rural population of about 800,000 and has treated over 40,000 cases of leprosy during the period 1955-75. Based on a stratified random sample of 25% of the case records, information was obtained about the profile of newly-detected cases in various cohorts (1955-57, 1958-60, 1961-64, 1965-69, 1970-75), regularity in drug collection and response to treatment. In newly-detected cases, the ratio of males to females was stable (3:2), but the proportion of adults aged 45 years or more increased from 15% in 1958-60 to 20% in 1970-75 and the lepromatous rate decreased from 9% to 6%; the proportion deformed at the time of diagnosis ranged from 11% to 15%. Regularity in drug collection was unsatisfactory even in the first year of treatment, with less than half the patients making 6 (or more) of the 12 monthly drug collections. The clinical status at 4-6 years was known for 70-75% of the patients who started treatment and of those approximately 60% had inactive or arrested disease. Data from population surveys was sparse; about 60% of the expected numbers were initiated and less than 30% of these had a coverage of 75% or more. The limited evidence, however, showed a decline in the prevalence of about 2 per thousand per annum. Field studies to evolve strategies for better motivation of patients, introduction of short-course regimens, and continuous monitoring of the programme are urgently needed.