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...

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.).

Erythema induratum leprosum, a deep nodular form of reaction in lepromatous leprosy

A chronic form of nodular lepra reaction in the lepromatous type of leprosy is described, characterized clinically by the presence of deep coalescing nodules on the forearms, hands, and thighs, and histologically by a proliferative vasculitis involving both arteries and veins of the hypoderm. There is also a massive leprotic panniculitis, more exaggerated than that commonly seen in the typical lepromatous nodule or in erythema nodosum leprosum.

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...

Mortality of persons with leprosy prior to sulfone therapy, Cordova and Talisay, Cebu, Philippines

1- A study is reported of the mortality of leprosy patients in Cordova and Talisay, Cebu Province, Philippines. The data are regarded as exceptionally accurate, having been derived from records of households inncluded in three surveys of Cordova (1933, 1941 and 1948) and two of Talisay (1936-37 and 1950-51), all made by the staff of the Leonard Wood Memorial in cooperation with the Department of Health of the Philippines. For Cordova, there are included 15 years of experience, 1933 to 1948, and for Talisay, 14 years, 1936-37 to 1950-51. Most of the bacteriologically positive patients had been treated for some years at the Eversley Childs Sanitarium. Sulfones were rarely used in therapy at that institution before 1947, and only for a few selected patients until 1951. 2- Standardized death rates have been computed for persons 15 years of age and over for each community and for both combined, by sex, for the total population, and for persons suffering from lepromatous or from nonlepromatous (tuberculoid or indeterminate) leprosy. For Cordova the second survey fortunately divided the experience at a critical point, and rates were obtained for the period 1933 to 1941, which are compared with those of the World War II period and the years immediately following, 1941 to 1948. 3- During the intervals between the initial and last surveys, for both communities combined, the average annual mortality for persons with lepromatous leprosy was 5.1 times that of the general population; for male patients the ratio was 5.1:1.0, and for females 4.4:1.0. Excess mortality over that of the general population was 71.7 per 1000 per year for patients of both sexes - 78.2 for male patients, and 53.3 for female. A larger experience is necessary to determine whether the observed greater excess mortality in males is a genuine characteristics or a chance variation. Patients suffering from the nonlepromatous forms did not have appreciably higher death rates than the general population. 4- Among lepromatous patients of both communities, the ratio of actual deaths to those expected at age specific rates prevailing in the general population. 4- Among lepromatous patients of both communities, the ratio of actual deaths to those expected at age specific rates prevailing in the general population was 4.0:1.0 for patients 15 to 29 years of age, 7.2:1.0 for those 30 to 49 years old, and 2.5:1.0 for those 50 years and over...

A field study of leprosy in Cordova, Philippines resurvey in 1941 after eight years

1- In 1933, a field study of leprosy was made in Corodova, Cebu, during which 99.6 per cent of the enumerated population of 6,063 inhabitants were examined. This includes 62 missed in the first survey but examined during a follow-up in 1935. Including patients already in segregation, the total prevalence in 1933 was found to be 19.0 per 1,000, 64 or 57.7 per cent of the 115 cases being of that type. 2- In 1941 after an eight-year interval, during which the population was kept under observation, a resurvey of the same area was made along lines similar to those followed in the first survey. Of an enumerated population of 7,026.98.9 per cent were examined. For total leprosy the prevalence rate was found to be 17.9 per 1,000, but for lepromatous leprosy it had decreased to 8.0 per 1,000, and lepromatous cases constituted only 44 per cent of the total of 126 cases found. 3- Of 49 patients with active lepromatous lesions in 1933, in segregation at the start of the study or found in the survey, 7 or 14 per cent became bacteriologically negative and were paroled during the eight-year period between the two surveys. Of 15 paroled before 1933, 4, or 27 per cent, lapsed during the same period, and 2 others of the 7 paroled after 1933 are known to have relapsed before 1941. The rate at which paroled lepromatous patients relapsed thus appears to be higher than the rate of parole over the same lenght of time...

Historical inquiry as a method of estimating the trend of leprosy

The records of Cordova and Talisay, Cebu, Philippine Islands, which have been the basis of several previous studies, have been utilized to illustrate the value of the historical method (as opposed to prolonged observation) in determining trend. A modified life table method of analysis was used. When the total experience of both communities was divided into years of life lived prior to and subsequent to January 1, 1915 and the study was limited also to the incidence of lepromatous leprosy only, it was found that there was evidence of a downward trend. The ratio of the incidence rate for the earlier to that for the later period was found to be, for males 1.3 to 1 and, for females, 2.0 to 1. Since in this comparison the later life experience of many persons exposed in the first period was included in the second, two groups of individuals were selected in such a manner that the life experiences of the groups were mutually exclusive. For the earlier period individuals born between 1896 and 1910 were selected and their life experience was included only to the year 1920. For the later period those born between 1911 and 1925 were chosen and their experience was included up to the year 1935. Thus, no individual in the first group was included in the second. Also all individuals, except those residing in the community less than ten years, had a minimum period of ten years of observation between entrance and termination of observation and none had more than twenty-five years of life experience. The downward trend of lepromatous leprosy was more strikingly evident in this second comparison than in the first. The ratio of the incidence rate for the earlier period to that for the later is for males, 2.0 to 1, and for females, 2.4 to 1. Evidently incidence had declined in the communities taken as a whole. The next question that arose was whether this downward trend could be detected in the experience of those who were known to have lived in the same household as a person with leprosy. Comparison was again made between the experience of those born between 1896 and 1910 and those born between 1911 and 1925. Only those who were known to have been living in household association with lepromatous leprosy were considered as exposed and their experience was contrasted with that of those for whom no history of exposure to any type of leprosy could be ascertained...

Risk of attack in leprosy in relation to age at exposure

A study of the life experience of 1520 individuals living in the province of Cebu, P. I., and exposed in the household to lepromatous leprosy reveals the following facts: 1- There is a clear relationship between age at the time of exposure and the risk of developing lepromatous leprosy. It is highest for those exposed before the age of 5 years, decreasing progressively as the age at time of exposure increases. This is true for both males and females. 2- The ratio of the incidence rates for males to those for females, for those exposed before 5 years of age, varies from 4.7:1 for rates in the age band of 5 to 10 years to 1.4:1 for those of 20 years and over. 3- The average interval between exposure and development of lepromatous leprosy was 10.5 years for those exposed under 10 years of age but only 6.0 years for those exposed after the age of 10 years.