Primary dapsone-resistant leprosy in Cebu, Philippines.

A survey of the prevalence of primary dapsone-resistant leprosy in Cebu, Philippines, has yielded an estimate of 3.6 per 100. Fifty-three of 55 patients proved to have M. leprae fully susceptible to dapsone. The organisms of two patients multiplied in mice administered the minimal effective dose of dapsone; and those of one of these patients also multiplied in mice administered dapsone in a 10-fold larger dose.

Evaluation of a new blood test for its potential to indicate leprosy infection prior to the appearance of clinical symptoms.

A test is described that utilized a laser nephelometric measure of the interaction between human serum and a leprosy biopsy suspension to demonstrate household contact with a leprosy index case. None of the test sera was from persons with clinical evidence of the disease. There was a 5:1 ratio of higher level reactors in sera from household contacts vs high level reactors in sera from persons in the surrounding community. This did not appear to be a result of age, sex, family relationship to the index case, or clinical character of the index case. Some index cases had high level serum reactors among their contacts; others did not. This phenomenon was not a function of the clinical classification of the index case. The reason is unknown. This test should provide another practical means to study leprosy.

The association between age of onset and mortality in lepromatous leprosy.

A life-table approach was employed to estimate expectation of survival of the non-leprous members of a population in which leprosy is endemic. The observed survival of members who developed lepromatous leprosy at different ages was compared with that expected after having attained the age at which onset occurred. Those whose onset occurred at later, as opposed to earlier, ages more frequently lived their expected remaining years of life. Survival was not decreased in those whose onset occurred after age 20. It is hypothesized that those whose onset occurs after maturity are more resistant to complications arising from infection with M. leprae which can lead prematurely to death.

Sensitivity and specificity of skin reactivity to Brugia malayi and Dirofilaria immitis antigens in Bancroftian and Malayan filariasis in the Philippines.

Saline antigen extracts of microfilariae, adult worms and third-stage larvae of subperiodic Brugia malayi maintained in gerbils were prepared for use as skin test reagents. Patients were studied on three different islands in the Philippines, one endemic for Bancroftian filariasis (Sorsogon, Luzon), another endemic for Malayan filariasis (Palawan) and the third without endemic filariasis (Cebu). A dose-response curve was established initially in patients with Bancroftian filariasis: thereafter 1.0 microng of the B. malayi antigens and 0.05 microng of Dirofilaria immitis FST antigen (obtained from Dr. T. Sawada) were used. Sizes of reactions were measured by recording the diameters of wheals at 20 minutes, 24 and 48 hours. There was a very high correlation in immediate hypersensitivity reactions among the three B. malayi antigens. Reaction sizes followed a normal distribution. When an area of an antigen-induced wheal 3 X that of the saline control was considered a positive reaction, 99% of 150 patients with Bancroftian filariasis and 96% of 45 subjects with Malayan filariasis reacted to B. malayi larval antigen. Only 68% of patients with Bancroftian filariasis but 90% of those with Malayan filariasis reacted to D. immitis FST antigen. There was no relationship between skin reactivity and age, sex, microfilaremia or severity of clinical disease. Approximately half of 50 patients who lived in an endemic area for W. bancrofti but had neither patent infection nor clinical disease reacted to B. malayi antigens. A maximum of 7% of 120 age- and sex-matched controls from Cebu gave false positive reactions with any of the antigens. Only a small proportion of patients gave 24- and 48-hour reactions. It is concluded that the use of antigens prepared from a human parasite, subperiodic B. malayi, which is easily maintained in a laboratory animal host, improves the ability to diagnose filarial infections by immunological means.

Some recent laboratory findings on Mycobacterium leprae. Implications for the therapy, epidemiology and control of leprosy.

From changes in the morphology and viability of Mycobacterium leprae in infected mice, some authors have concluded that the majority of smear-positive human lepromatous patients become non-infectious within 3-4 months of the beginning of regular treatment with sulfones, even at dosages equivalent to only one-hundredth of the conventional daily dose-namely, 1 mg daily. These very low dosages have, however, not been advocated because of the risk that resistant strains of Myco. leprae might develop. The laboratory findings have already been applied to human leprosy by some leprologists; if they were more widely adopted, leprosy programmes could be seriously affected and the consequences could be serious in endemic areas. Contrary to the results of laboratory tests, the shortcomings of clinical sulfone therapy are evident all over the world from the long times required for lepromatous cases to become bacteriologically negative, from the high proportion of relapses and from chemoprophylaxis trials in child contacts. Final proof of the relationship between the morphological index, i.e., the proportion of solidly staining bacilli present, and contagiousness can come only from prolonged and well-planned epidemiological studies. It appears that leprosy may develop in appreciable numbers of child contacts exposed to index cases already bacteriologically negative, with or without prophylactic dapsone treatment.The results of controlled BCG trials now in progress are not consistent although laboratory trials in mice have indicated that BCG vaccination confers a high degree of protection. However, the results that have been obtained in the mouse, an unnatural host, may not be obtainable in man.It is considered premature to apply laboratory findings to human leprosy before clinical and epidemiological studies have been made in man.

Lepromin vs purified bacillus suspension. II. Comparative tests with a purified bacillus suspension

Comparative tests of Wade's "purified acillus suspension" and the standard lepromin prepared from the same pool of leproma have been made in the Philippiones, Netherlands New Guinea, East Africa and South Africa. Consistently in the comparisons the standard lepromin gave more positive Mitsuda reactions, or more strong reactions, than the suspension; and in the healthy children tested the PBS sometimes gave negative results when the reactions to lepromin were positive. For this reason alone it would not be satisfactory for use in field work in which children are involved. Lepromin gave more early reactions than the suspension in the cases for which that effect was reported (Philippines), suggesting that in the preparation of the latter the immediately-available antigenic elements had partly been eliminated. The suspension on the whole caused somewhat less ulceration of the reaction lesions, which is a point in its favor. However, contrary findings were not infrequent, so use of the product could not be advocated strongly on that ground. The results in tuberculoid cases permit comparison of the reactivities of the four different regional groups, whether considering average sizes of the reaction lesions or the percentage of the stronger reactions. Despite the high percentages of positive reactors in the Philippine subjects, the New Guinea people proved to be distinctly more so, and the East African cases the most reactive of all. The South African cases were much less reactive in comparison. The question of why people living in different environments differ materially in reactivity remains an intriguing problem.