A sequential study of circulating immune complexes, complement and immunoglobulins in borderline tuberculoid leprosy patients with and without reactions.

Sequential estimates of the levels of circulating immune complexes (CIC), complement catabolic fragment C3d, complement-mediated immune complex solubilization (CMS) and immunoglobulins were made in 24 newly diagnosed with borderline tuberculoid leprosy over a 20 month period after initiation of chemotherapy. Fourteen of these patients had not suffered from reversal reactions either at the time of presentation or during the follow-up. The levels of CIC were evaluated in them from the third to the eleventh month after starting chemotherapy and immunoglobulin G (IgG) levels were evaluated up to eight months. The concentrations of C3d and immunoglobulins A (IgA) and M (IgM) were normal in these patients. The other ten patients had reversal reaction at the time of diagnosis which subsided by the third month after starting treatment. They did not have reversal reactions later. The levels of CIC and IgG were elevated and those of CMS were depressed throughout the study period. Serum C3d level was initially elevated but came down to normal by the third month while IgA and IgM levels were within normal limits. The relevance of these findings to the genesis of reversal reaction is discussed in this communication.

A sequential study of circulating immune complexes, complement and immunoglobulins in borderline tuberculoid leprosy patients with and without reactions

Sequential estimates of the levels of circulating immune complexes (CIC), complement catabolic fragment C3d, complement-mediated immune complex solubilization (CMS) and immunoglobulins were made in 24 newly diagnosed with borderline tuberculoid leprosy over a 20 month period after initiation of chemotherapy. Fourteen of these patients had not suffered from reversal reactions either at the time of presentation or during the follow-up. The levels of CIC were evaluated in them from the third to the eleventh month after starting chemotherapy and immunoglobulin G (IgG) levels were evaluated up to eight months. The concentrations of C3d and immunoglobulins A (IgA) and M (IgM) were normal in these patients. The other ten patients had reversal reaction at the time of diagnosis which subsided by the third month after starting treatment. They did not have reversal reactions later. The levels of CIC and IgG were elevated and those of CMS were depressed throughout the study period. Serum C3d level was initially elevated but came down to normal by the third month while IgA and IgM levels were within normal limits. The relevance of these findings to the genesis of reversal reaction is discussed in this communication.

Psychosocial aspects of deformed leprosy patients undergoing surgical correction.

A psychosocial study was conducted on 25 randomly selected leprosy patients undergoing corrective surgical procedures for their deformities. High anxiety and depression levels found preoperatively, reduced significantly after operation. Psychiatric assistance is needed for these patients in order to clear their psychic aberrations, create awareness, boost morale and to give self-confidence. Only 50-75% of preoperative expectations were satisfied but that was only in 40% of patients. This calls for a preoperative counselling session with the patients to help them reach the realistic goals that they can achieve. They should be told what benefits surgery can offer them and be made aware of the problems which will persist after operation, such as anaesthesia and analgesia.

Persistent reduced solubilization of immune complexes in lepromatous leprosy patients with reactions.

It is held that immune complexes (IC) play a vital role in the pathogenesis of some of the reactions in leprosy. The complement system is known to solubilize and render IC innocuous. We have previously shown that patients undergoing lepra reactions had lowered complement-mediated IC solubilization (CMS). We, therefore, undertook a prospective study of untreated multibacillary leprosy patients and monitored their CMS levels sequentially while on therapy. In addition, the concentrations of the complement component C3d, immunoglobulins G, A and M, and circulating immune complexes (CIC) were also estimated. A total of 26 patients were included in the study and were investigated at 3-month intervals for 3 years. Thirteen of the 14 patients who did not develop reactions at all had normal CMS values, although all of them showed elevated CIC. From the inception of treatment, 10 of the 12 patients who developed lepra reactions had low CMS values which remained below normal levels even after evidence of complement activation disappeared and long after the subsidence of reaction. It is suggested that this defective CMS acts as a predisposing cause of lepra reactions.

Effect of chemotherapy on viability of Mycobacterium leprae as determined by ATP content, morphological index and FDA-EB fluorescent staining.

Viable bacterial populations were estimated in bacilli purified from 105 biopsies from 40 untreated and 65 multibacillary leprosy patients treated with multidrug therapy (MDT) for varying periods. The bacilli were purified and viability was determined by ATP content, morphological index (MI), and fluorescein diacetate-ethidium bromide (FDA-EB) staining. Viable populations were calculated, taking 3.58 x 10(-15) g/solid bacillus as the mean ATP content of a viable unit of Mycobacterium leprae. The proportion of viable bacilli was also estimated in the same specimens using solid-staining (MI) and green-staining bacilli by the FDA-EB method. In the untreated cases, the positive viability by ATP assay was 100%, 92% by MI, and 100% by FDA-EB. ATP content per solid bacillus was relatively constant, which was not the case with ATP content per green-staining bacillus. While the MI was zero in all cases, viable bacilli could still be detected by ATP estimations in 5 of the 32 (16%) patients after 2 years of MDT and in 1 of the 20 (5%) patients after 3 years of MDT. No viable bacilli could be detected even by this method beyond 3 years of MDT. On the other hand, green-staining bacilli were demonstrable in 7/32 (22%) of cases after 2 years of MDT, 2/20 (10%) after 3 years of MDT, and 1/13 (8%) after more than 3 years of treatment, indicating that the FDA-EB staining and ATP assay did not detect the same populations. A determination of the ATP content of M. leprae could be used as a reliable and sensitive tool for determining viability of the bacilli.

Relapses in paucibacillary patients after treatment with three short-term regimens containing rifampin.

Three multidrug regimens all containing rifampin and dapsone have been tried for the treatment of 278 cases of paucibacillary leprosy. Regimen I was the one recommended by the WHO Study Group. Regimen II was the same as Regimen I with depsone alone continued for a further 6 months. Regimen III was the same as Regimen II but rifampin was given daily for the first 7 days. The patients were comparable with regard to disease classification, lepromin status, bacteriological status, and number of lesions. As reported earlier, the disease inactivity rates by 1 year of treatment were much greater with Regimens II and III than with Regimen I (94% and 97% vs 76%). Early reaction was seen in 6% of those in Regimen III and in none in Regimens I and II. Late reaction was observed in 9% of those in Regimen I and none in Regimens II and III. During 3 1/2 years of follow up, 13% of the cases in Regimen I, 1% in Regimen II, and 2% in Regimen III relapsed. Since the patients in the three regimens were otherwise comparable, it is concluded that the high inactivity rate, low relapse rate (1%-2%), and no early or late reaction as observed in Regimen II patients were because of adequate treatment.

Results of a modified WHO regimen in highly bacilliferous BL/LL patients.

A regimen consisting of 600 mg of rifampin once a month, 100 mg of clofazimine on alternate days, and 100 mg of dapsone daily was used in 56 untreated, highly bacillated borderline lepromatous/lepromatous (BL/LL) patients with an average bacterial index (BI) of 4.45. Treatment was continued until skin-smear negativity. After 2 years of therapy, none of the patients had become smear negative and the average BI was 2.56. There was no growth on inoculation of skin-tissue biopsies in the normal mouse foot pad after 6 months of therapy. Bacillemia was still detectable in 11/50 patients, and significant ATP levels were detected in Mycobacterium leprae from skin-tissue biopsies in 16% of the cases. After 3 years of therapy, three patients had become smear negative. The average BI was 1.30. None of the patients had detectable bacillemia, and 5% of the cases showed detectable ATP levels in M. leprae from tissue biopsies. After 4 years of therapy, 41.7% of the patients had become smear negative. The average BI was 0.66, and no ATP was detected in any of the purified bacillary suspensions. The fall in BI was accelerated, and more patients on continued treatment became negative earlier compared to those having treatment for a limited duration, as reported by others.

Pyrazinamide as a part of combination therapy for BL and LL patients--a preliminary report.

Pyrazinamide in a dose of 1500 mg was given to 63 borderline lepromatous (BL) and lepromatous (LL) leprosy patients on different drug regimens for the initial 2 months of therapy. Fifty-one BL and LL patients were put on the same drug regimens without pyrazinamide. There was a rapid and good clinical improvement in the patients in both of the groups. At the end of 2 years, the patients who received pyrazinamide had a morphological index (MI) of zero as compared to those patients who did not receive pyrazinamide, some of whom still had solidly staining bacilli. One out of 20 (5%) scrotal (smooth muscle) biopsies of the patients who received pyrazinamide had growth in the mouse foot pad as compared to 9 out of 38 (23.7%) smooth muscle biopsies of the patients who did not receive pyrazinamide. At the end of 5 years, the patients who received pyrazinamide had slightly better results compared with the non-pyrazinamide group. Pyrazinamide appears to have some effect against persisters in multibacillary leprosy. A well-controlled, randomized trial with longer duration of pyrazinamide therapy in a larger group of patients needs to be carried out to unequivocally determine the exact role of pyrazinamide in leprosy.

Comparison of three regimens containing rifampin for treatment of paucibacillary leprosy patients.

Three regimens containing rifampin have been tried in paucibacillary leprosy patients. The patients were selected according to the criteria laid down by the World Health Organization (WHO). In Regimen I, rifampin 600 mg is given once a month for 6 months with dapsone 100 mg daily. Treatment is stopped at the end of 6 months. Regimen II is the same as Regimen I, and is supplemented with an additional 6 months' treatment with dapsone 100 mg daily. Regimen III is the same as Regimen II, except that rifampin is administered daily for the first 7 days. At the end of the scheduled treatment period, 72.2% of the patients in Regimen I, 94.9% of the patients in Regimen II, and 97.1% in Regimen III became inactive. Eighteen out of the 25 active cases at the time Regimen I treatment was stopped had to be restarted on drug therapy since they showed a worsening of their disease, as indicated by an increase in their bacterial index, the appearance of new lesions, renewed activity in old lesions, an increase in the size of old lesions, or development of nerve abscesses. The remaining seven cases regressed without further treatment. All four Regimen II patients and two Regimen III patients who had evidence of activity at the time treatment was stopped did not require any further treatment. On follow-up for 1 1/2 years, three Regimen I patients and none of the Regimen II or Regimen III patients showed relapses. It is thus apparent that rifampin helps to shorten the time duration and to increase the cost effectiveness of treatment of paucibacillary leprosy cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Follow up of BL/LL patients on a slightly modified WHO regimen of multidrug therapy.

56 lepromatous leprosy patients with an initial average BI of 4.45 were administered once a month 600 mg of Rifampicin, 100 mg of Clofazimine on alternate days and 100 mg of Dapsone daily. None of these patients became smear negative in 2 years, and the same regimen was continued further. Two patients have become negative in 3 years and treatment has been stopped in them. The study indicates that highly bacilliferous LL/BL patients are likely to need 3 years or more of MDT for achieving bacterial negativity.

Dermatoglyphics in leprosy (II Metric analysis of palms).

A group of 100 leprosy patients consisting of 50 lepromatous (BL/LL) and 50 tuberculoid (BT/TT) were investigated for metric analysis of the patterns present on their palms. Hundred normal persons were also selected from the families of patients to serve as controls. BT/TT patients and controls did not show any significant difference in their palmar patterns. On the other hand, significant differences were observed in the patterns between BL/LL patients and controls.

Chemotherapeutic trials with different regimens containing rifampicin in paucibacillary type of leprosy cases--a preliminary report.

Different regimens containing Rifampicin have been tried in treating paucibacillary leprosy patients. In our study we have studied three regimens. Regimen I consists of treating patients with Rifampicin 600 mg once a month for six months combined with Dapsone 100mg daily and treatment is stopped at six months. Regimen II is same as regimen I except that instead of stopping treatment at the end of six months the treatment was continued with dapsone 100 mg daily for another six months and treatment was stopped at one year. Regimen III is the same as recommended by I.A.L. in which treatment is started with Rifampicin 600 mg daily for seven days in the first month to be followed by Rifampicin 600 mg once a month for five more months. This is combined with dapsone 100mg daily for one year. Treatment in this group is also stopped at one year. Eighty one patients in Regimen I, thirty five patients in Regimen II and sixty three patients in Regimen III completed the six month treatment. It was found that the inactivation index in all the three regimens was nearly the same.

A study of the cause of irregularity of patients attending the out patient department of Cjil, Agra.

A study of 195 patients attending the out patient department with regard to regularity is reported. 71 patients or 36.41% were found to be irregular. The causes of irregularity were found to be predominently socio-economic factors. Since irregularity may lead to emergence of drug resistance due to irregular, inadequate and interrupted drug compliance, socio-economic factor require amelioration.

Dermatoglyphics in leprosy (I. Finger patterns).

Finger dermatoglyphic patterns were studied in leprosy families selecting patients and controls from each family. A total of 100 leprosy cases (50 of TT/BT types and 50 of BL/LL types) and 100 control subjects were investigated. While a statistically significant association was noted with some finger patterns (loop ulnar, loop radial, loop twin and loop central pocket) in the lepromatous type, no such association was observed with the finger patterns in the tuberculoid type.

Attitude of doctors to working in leprosy.

A study was conducted to assess the attitude of Doctors to working in leprosy. 35 subjects were studied using a questionnaire to tap the various areas of leprosy work. The results indicated that although a majority of the doctors were interested in the specialty and considered that they had been trained well there was evidence of inadequate knowledge in 33% of them. Fears of being socially stigmatised and facing poor job prospects while working in this field were also revealed. It is suggested that training in the under-graduate and, post-graduate levels and improving job prospects would remove the disincentives which hamper anti-leprosy work.

Solid, fragmented and granular index as one of the parameters in drug trials.

A bacteriological study of the skin smears of 108 bacteriologically positive cases of leprosy, 30 of them untreated, has been undertaken. In each case solid, fragmented and granular (SFG) index, bacteriological index (BI) and morphological index (MI) of skin smears from 4 sites were calculated. The results show that SFG index together with BI can be used as one of the parameters in drug trials. The importance of SFG index in research and as a routine laboratory procedure in leprosy control units undertaking multi drug therapy is discussed.