Along with the systematic studies on the treatment of leproy patients with RFP, which were projected by the Squad of Antileprosy Chemotherapy, the pharmaceutical view of this antibiotics was outlined, in order to provide facility for the clinical field in leprosy study.

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This trial has been carried out by thirteen National Leprosaria and the National Institute for Leprosy Research since October, 1971. Observation has been made clini cally, bacteriologically, histopathologically and serologically at regular intervals through the trial.
Pure lepromatous cases were selected and divided into following five groups, i.e., Group A, B, C (C-1, C-2) and D. Group A consisted of untreated new cases, and Group B relapsed cases. Group C consisted of so-called resistant cases ; and divided into C-1 and C-2 according to the duration of the past treatment. Group C-1 were cases showing poor recovery in B.I. though treated regularly more than five years. Group C-2 were clinically aggravated cases by regular treatment more than one year. Group D were cases which confronted with blindness.
The numbers of cases in this trial were 76 in total. Numbers of cases in each group were as follows ; Group A 4, Group B 9, Group C-1 55, Group C-2 5 and Group D 3.
We administered RFP 450 mg orally before breakfast at a time. Two different methods of administration were compared ; twice a week and six times a week methods. We made a rule to use DDS together with RFP except for the Group D. The dose of DDS was gradually increased and reached the maximum dose, 75 or 100mg daily at the nineth week.
Among 76 cases, 40 cases finished the scheduled administration of RFP for twelve months. 17 cases dropped from the trial by some reasons (Table 14). In the remaining 19 cases the treatment did not reach to twelve months yet. Clinical results of these 40 cases were shown in Table 6-7. As shown in these tables, all of these 40 cases which were administered RFP for twelve months showed effective results. In Group C-1 with poor response for sulfon treatment in the past, RFP was very effective. As for Group 8 9 A, B, C-2 and D, even though their numbers were too small to get a clear conclusion, favourable results were also obtained. We could not find statistically significant differences between two days method and six days method on clinical effect, fall of B. I. and MI., and frequency of ENL.
The reasons of interruption of RFP administration in 17 cases were as follows, ENL or eye complications in 8 cases, borderline reaction in 2 cases, gastric disturbances in 2 cases, extra-medical reason in one case and high fever shortly after the intake of RFP in 4 cases. This symptom of high fever shortly after the intake of RFP was observed mainly in the fifth and sixth month since the start of administration. It is noticeable that these cases were found only in the two days method group. The symptom was suspected of allergic nature to RFP, but in some cases it was difficult to distinguish clini- cally the allergic response from ENL.
Gastric disturbances were the most frequent side effects during the treatment, but they were not so severe. Three cases complained of itching or paresthesia after intake of RFP. Transient increase of S-GOT and GPT values was observed in 2 cases. One case showed thrombocytopenia, which recovered after stop of RFP administr-ation.
The fall of M.I. during the treatment was satisfactory in almost all cases. Decrease of B.I. in twelve months was slight but statistically significant in C-1 Group.

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Seventy-six patients with typical lepromatous leprosy were treated with rifampicin (RFP) and DDS for twelve months, and the morphological index (MI)^a of fifty patients of them have been measured on 0, 1/2 1, 3, 6, 9 and 12 months after the start of treatment.
At the pretreatment, twenty-eight patients (56%) had more than 3% of the solidly stained bacilli in their skin smears, but the granular-formed bacilli, generally, had been prominent on the starting point. Because most of the cases were poor recovery in the bacterial index though treated with sulfones or other anti-leprosy drugs for over five years regularly.
In the greater part of the cases, it has been found that the MI decreased very rapidly, on the other hand, the granular bacilli (GI)^b quickly increased within a month after the start of treatment (table 1, 4, fig. 2 and 3).
After three months of treatment the average value of the GI was 82%, then it was gradually increased and most of the bacilli (92%) had become granular at twelve months (table 2, 3 and 5).
From the results of the MI as an indicator, 9 out of the 50 patients were improved markedly, 21 were moderately, 13 were slightly and 7 were poorly. As a whole, there were more than 85% of patients who were clearly improved the MI, even then including the " resistant cases" in this trial (table 6).
There has been no difference between the six-day method and the two-day method of RFP for the decrease of the MI, and the therapeutic effect has been able to expect satisfactory in both methods.
During the treatment of 12 months, no increase in the MI was found in all cases and the appearence of the RFP-resistant bacilli was not confirmed. Furthermore, the average bacterial index was decreased very slowly but significantly during the treatment.
In conclusion, the decrease of the MI in patients treated with RFP is as rapid as or more rapid than in those treated with other anti-leprosy drugs.
^aEach cases has been prepared two skin smears from different part of the lesions at the same time, and the MI is found by examining the morphology of 400 bacilli.
^bThe granular index means percentage of the granular bacilli in the total.
^cRFP was administered in an oral dosage of 450mg. Two-day method was received twice a week and six-day method was six times a week.

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We have investigated histopathologically a therapeutic effect of rifampicin on biopsies sent from ten leprosaria in Japan. The number of specimens in pretreatment was 70 cases, but it decreased to 40 and 42 cases respectively at sixth month and one year after treatment. Because it was caused by side-effect including the reaction in early stage (see Report 1). Specimens of C-1 group (resistant or incurable case to DDS) were overwhelming majority (65.7%) compared with other group (see table 1 & 2) in pretreatment. Accordingly, the evaluation of the effect of rifampicin was principally carried out on C-1 group rather than comparison with non-treated control group.
As the size of leproma in the pretreatment stage differs in each specimen, it was conveniently devided in five types histopathologically according to the shape, extent and size, i. e. large-nodular type, diffuse-infiltrated type, scattered-infiltrated type, slightinfiltrated type and minimal-infiltrated type.
It was found that these types transformed rapidly toward a smaller one during treatment of RFP+DDS, and the number of Mycobact. leprae in the leproma decreased rapidly and form of bacilli changed to granular, and finally they disappeared conpletely in some cases. So it was considered that effective rate of rifampicin was high (75%), and it went far over the limit of sulfone therapy.
Concerning to the healing process it was noticed that a scar formation or remarkable fibrosis with remnant foci consisted of a few epithelioid cells and/or foamy cells in the corium were observed at the short period considerably (one year after treatment), and in some cases foci enlarged temporally with proliferation of epithelioid cells, lymphocytic infiltration and appearance of giant cells, that is, so-called " epithelioid cell reaction" after six months (Fig. 2).
However, a few case was thought to be resistant to rifampicin from the results of ineffective or worse cases. Therefore in future more strict attention have to be paid to them.

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In order to know the effect of Rifampicin (RFP) on immunological state of leprosy, the sera of lepromatous patients treated with the combined use of RFP and DDS were examined at 3 months intervals, for a period of one year, by the following tests : fluorescent leprosy antibody absorption (FLA-ABS) test, Leproagglutination, i.e., an agglutination of kaolin particles coated with cardiolipin-lecithin (1:1) and the electrophoresis on cellulose-acetate membrane.
The antibody-titer of FLA-ABS test dropped temporarily during the treatment and then tended to rise at 12th month. Such a fall of antibody-titer was more conspicuous in the patients who caused ENL under the treatment than in the cases without ENL. The titer of Leproagglutination test showed similar temporary fall in the latter cases, but not in ENL cases. In 2 cases of patients who caused borderline reaction under the treatment, FLA-ABS titer was on the decline after the reaction subsided. Immunoglobulins M and G were found to participate in this test and the titer of respective immunoglobulins underwent similar changes as described above.
Among serum protein fractions only α2-globulin showed temporary drop of the level in the cases without ENL. No significant difference was found in lepromin reactions examined before and after the treatment. The implcations of these findings were discussed from a view-point on immunology of leprosy.

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In 1931 the leprosy control program by segregation policy came into operetion by local Government according to the Leprosy Prevention Law in Japan. Since then, in 1961 the Ryukyu Government issued the new law to change the policy for leprosy control and started out-patient treatment for the patients at several places in 1962.
From 1931 to 1972, about 3735 leprosy cases have been detected and controlled during 41 years. On the number of the newly-detected patients by each year the analysis has been done epidemiologically by leprosy incidence rate, lepramatous ratio, lepromatous incidence rate, age and sex. The conculusions are as follows ;
1. During the first 5 years when out-patient treatment came into operation since 1962, the number of newly-detected patients has increased from 70 cases in 1962, to 173 cases in 1967. Then the number has decreased from 173 to 70 in 1972 during the 2nd 5 years. The increase during the first 5 years is mainly due to the change poicy on leprosy control. The patients are willing to gather to O.P.D. for treatment. The decrease during the 2nd 5 years cause by the effect of leprosy control policy successfully, because many slight and early cases were detected in O.P.D. or other medical institutions, public health unites, centers, general hospitals and private practitioners.
2. The out-patient treatment of leprosy patients in Okinawa Island for ten years proved to be successful for leprosy control.

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