Cutaneous responses to lepromin and to other mycobacterial antigens. (Human, avian and battey tuberculins, and human and avian tubercle bacilli)

A comparative study has been made of the reactions in healthy Cebu children to lepromin, to human, avian and Battey PPD's, and to heat-killed suspensions of whole M. tuberculosis and M. avium. The bacillary suspensions were given only to nonreactors to the homologous tuberculins to avopid violent reactions and on the assumption that all tuberculin reactors would have responded to the homologous whole bacillus antigen. Of the 746 children in the study, 15.3 per cent gave positive early lepromin (Fernandez) reactions, while 74.1 per cent showed positive late lepromin (Mitsuda) reactions. Of these children 194 had been vaccinated with BCG at some time in the past; there was no difference between these children and others with respect to the frequency of either early or late reactions ....

The epidemiology of leprosy present status and problems

Wemay conclude that our knowledge of leprosy has been substantially extended since the day eighty years ago when Hirsch could see little that was hopeful. Additional and more convincing evidence of its contagiousness has been obtained. Although direct proof is still lacking that M. leprae is the etiological agent, the evidence is strongly in that direction and promising experimental studies are under way. A great deal has been learned concerning the clinical varieties, and especially concerning the frequency and importance of the tuberculoid type. The lepromin test now provides helpful information as to the resistance of the individual. Field studies have defined, much more precisely than before, the relative risk of household association with persons sufffering from the lepromatous and nonlepromatous forms, respectively, and the influence of sex and of age. There is much more that could be learned, and some suggestions regarding future field studies have been made. Perhaps the major difference between the present and the past is that we now have a good working hypothesis, admittedly with many weak points, but one that is coherent and in accordance with current biologic thought.

Clinical evaluation studies in lepromatous leprosy fourth series: 4, Butoxy-4dimethylaminodiphenyl thiourea (DPT), amodiaquin, and 4-4 diaminodiphenyl sulfone (DDS) 2.5 mgm. and 4 mgm. per kg. of body weight

In a duplicate experiment on lepromatous leprosy carried out at two leprosaria in the Philippines, Central Luzon Sanitarium near Manila and Eversley Childs Sanitarium near Cebu City, four groups of patients were treated respectively with 4 butoxy - 4' dimethylaminodiphenyl thiourea (SU 1906), amodiaquin (camoquin), a higher dose of DDS (4 mgm. per kgm. of body weight) and a lower dose of DDS (2.5 mgm. per kgm.) Treatment was continued for 96 weeks, except in the amodiaquin group in which the drug was discontinued at 72 weeks; most of the patients of this group were continued on DDS. At both institutions the superiority of DDS over amodiaquin was evident from the physical examinations at 72 weeks, and this was confirmed at 96 weeks in spite of the fact that most of the amodiaquin patients had received DDS from the 73rd week. SU 1906 likewise was superior to amodiaquin. In comparison with both higher and lower doses of DDS, however, SU 1906 showed consistently lower rates of improvement at each examination, but the differences were small. The patients on the higher dosage of DDS did not improve in greater proportion than those in the lower dose, as far as the clinical evidence goes. As had been found in our previous studies, healing of ulceration of the nasal septum took longer than is usually supposed, and new ulcerations occurred under continuous therapy with either DDS or SU 1906. At Eversley Childs, where the treatment schedules were more closely adhered to than at Central Luzon the value of sulfone treatment was indicated by a higher percentage of healing and a lower frequency of patients developing new ulcerations...

The need for study of the potentials of surgery and physiotherapy in leprosy

The problem may be summarized as follows: The number of persons suffering from leprosy is very large - certainly several millions, scattered over a wide geographic area but for the most part in warmer climates. Disability is present in more than one-half of existent cases, and occurs ultimately in nearly all. This varies from a slight handicap with only contractures of the fingers to total physical disability with extensive loss of distal parts of the limbs. Disability occurs earlier in the tuberculoid than the lepromatous type, but in the end it is equally frequent in both types It is accompained and contributed to by loss of perception of pain, light touch, and change in temperature in the areas supplied by the affected nerves. Involvement of the temporal and zygomatic branches of the facial nerve is very common and frequently bilateral, leading to inability to close the eyelids tightly with consequent exposure of the cornea to injury. Invasion of the eye, infiltration and nodulation of the skin of the face and ears, ulceration, and scarring add to the deformity in the lepromatous type. Absorption of the bones of the hands and feet has long been considered and inevitable consequence. Recently a more hopeful outlook for prevention has been presented. It is claimed that in a substantial proportion of patients the shortening and eventual loss of difits is caused by secondary infection of wounds or abrasions, to which the anesthetic hand and foot are especially subject. If this view is correct, the prevention of infection becomes a matter of greatest importance. Final considerations which add to the seriousness of the problem are that nerve damage is present in many patients on discovery, and that present-day chemotherapy cannot bu counted on to reverse, and probably not to limit, the degenerative process in the nerves. This latter statement should not be interpreted as implying that early sulfone treatment may not have a beneficial effect, but only that such an effect has not yet been demonstrated.

The origin of natural reactivity to lepromin. The association between the Mitsuda reaction and reactions to graded doses of tuberculin

This study deals with lepromin reactivity of the Mitsuda type, observed in apparently healthy children on MActan Island, Cebu, Philippines. The principal theories which have been offered to explain this type of reactivity are prior infection with M. leprae, with M. tuberculosis, or with some other species of mycobacteria. It is improbable that the majority of these children, and especially those under three years of age, could have been exposed to leprosy. Although there is a positive correlation between reactivity to tuberculin and that to lepromin, the excess of lepromin reactors among tuberculin positives over the number e´xpected if there were no association comprises a very small fraction of the total number reacting to lepromin. This is true both for small doses of tuberculin, reaction to which is regarded as specific for infection with M. tuberculosis, and for larger doses which may indicate prior infection with other species of Mycobacterium. This suggests that lepromin reactivity among these children is caused in most instances by some factor other than infection with M. tuberculosis or any related species. The theory that the test dose of lepromin is the responsible sensitizing factor is not in itself adequate as far as can be judget from the effect of a second lepromin test in a controlled study...

Clinical evaluation studies in lepromatous leprosy. Third series: nicotinamide, and BCG vaccination as supplements to diaminodiphenyl sulfone (DDS)

In a triplicate therapeutic experiment on lepromatous leprosy carried out at two leprosaria in the Philippines and one in the Union of South Africa, two major groups of patients at each institution were treated respectively with diaminodiphenyl sulfone (DDS), and with DDS plus nicotinamide. Tuberculin-negative patients of each group were divided into two subclasses. The patients of one subclass were vaccinated at least once with BCG; those of the other were left unvaccinated. Treatment was continued for 48 weeks. No evidence was found that either supplementary therapy with nicotinamide or vaccination with BCG was advantagenous. Patients of all subclasses showed clinical and bacteriologic improvement, but those treated only with DDS and not vaccinated showed about the same progress as others. Observed clinical improvement was limited to dermatologic lesions; there were no significant changes in the extent of anesthesis associated with any of the therapies. Only 6 of 434 patients at all institutions developed lepromin reactivity of the MItsuda type, and in all of these the size of the reaction was small. The occurrence of the reactional condition, erythema nodosum leprosum, was not associated with either clinical or bacteriologic improvement. It was equally frequent in the two principal therapy groups, was not evoked by BCG vaccination, and was not associated with reactivity to PPD (0.0001 mgm.).

Clinical evaluation studies in lepromatous leprosy second series: isoniazid and diasone (diamidin) isoniazid and dihydrostreptomycin also a pilot study with streptohydrazid

1- There is described a controllled therapeutic study of lepromatous leprosy which was carried out concurrently at the Central Luzon Sanitarium and the Eversley Childs Sanitarium in the PHilippines, and the Westfort Institution in South Africa. At Central Luzon, 213 patients commenced and 187 completed 48 weeks of treatment; at Eversley Childs, 234 commenced and 202 completed; and at Westfort, 119 commenced and 111 completed. 2- At each institution the patients were dicided into three matched groups, A, B, and C, taking into consideration sex, age, stage of disease, prior sulfone therapy and certain other factors. Group A received diasone (diamidin) in the Standard dosage; Group B received diasone in the same dosage as A, plus isoniazid (INH), 10 mgm. daily per kgm. of body weight; Group C received the same dosage of INH as B, plus 1 gm. dihydrostreptomycin (DHSM) intramuscularly twice weekly. 3- All therapies were well tolerated. The principal cause for discontinuance of treatment was departure from the institution without permission. As the groups were constituted at the end, however, they were comparable to one another inasfar as this could be determined. 4- On completion of treatment the proportion of each group, at each institution, showing clinical improvement was approximately the same. This was true of general improvement and of improvement in specified lesions such as infiltration, ulcers, nodules and others. A very small proportion became worse, and in this respect there was no evident relationship to any particular therapy. 5- No evidence was obtained that clinical improvement may be related to age, sex or other background factors, except prior sulfone therapy and stage of the disease. At all institutions, patients who had received little or no sulfone therapy before entering the study showed a higher clinical improvement rate than those who had been treated for a year or more. Also at all institutions the L2 and L3 patients taken together showed higher proportions of improvemment than those classed as L1. The patients in whom the disease was more advanced, however, were likewise those who on the average had received less sulfones before entering the study. Unfortunately the numbers of cases were too small to yield improvement rates for patients in various stages of the disease classified as to amount of prior sulfone therapy...

Effect of BCG vaccination, lepromin testing and natural causes in inducing reactivity to lepromin and to tuberculin

1- A report is made of an effort to determine the relative importance of natural causes, initial lepromin testing, and vaccination with BCG in producing reactivity to lepromin and to tuberculin. The possibility is admitted that the final lepromin test may itself cause reactivity of the Mitsuda type but there is no available means of separating this efffect from that of natural causes. 2- The subjects were 550 apparently healthy children, 6 months to 35 months of age, having no known contact with leprosy, living in their homes on Mactan Island, Cebu, Philippines, of whom 483 completed all requirements of the study. 3- A random sample of one-fifth constituted a basic control group, given initially only a tuberculin test (PPD-S, 0.0001 mgm.). The remainder were tested with lepromin and PPD-S, and those negative to both were divided at random into four subgroups. Two were vaccinated intradermally with BCG, one with a fresh preparation and the other with a lyophilized one. The other subgroups were given diphtheria toxoid and saline, respectively. Ninety to 100 days after the BCG and other inoculations, and, on the average, 143 days after the initial tests, all children including the basic controls were tested with lepromin and PPD-S of the same lots, and in the same dosages, as those used at the outset...