| Status | Medical Researcher |
|---|---|
| Country | USA |
Dr Louis Levy’s contribution to leprosy work has involved extensive research into the chemotherapy of drugs, especially dapsone, but also rifampin and clofazimine. In the process he has investigated the viability of M. leprae extensively, using the mouse footpad model.
Born in New Jersey in 1927, Dr Levy gained his BA in 1947 at the University of Pennsylvania, in Philadelphia. Between 1950-51, as a Life Insurance Medical Research Fund Predoctoral Fellow, at the Department of Biological Chemistry, in the School of Medicine, at the University of Pennsylvania, he conducted research into an aspect of “intermediary metabolism” which resulted in the following publications: L Levy and MJ Coon, "The role of formate in the biosynthesis of histidine", J Biol Chem 192(1951): 807 and L Levy and MJ Coon,"Biosynthesis of histidine from radioactive acetate and glucose" J Biol Chem 208 (1954): 691.
After he completed his MD in 1952, at the University of Pennsylvania, he was assigned to an Indian Service tuberculosis hospital in South Dakota. He served as the Medical Officer in Charge of the Sioux Sanatorium, situated in the Black Hills, near Mount Rushmore (1953-1956). He subsequently accepted a residency in internal medicine at the Public Health Service (PHS) Hospital, Staten Island, New York and was then assigned to the PHS Hospital (a general hospital), in San Francisco.
Between 1959-1962 and 1964-1965, he worked as Assistant Chief in the medical service at the Public Health Service Hospital, in San Francisco, and between 1965-1976, he was Assistant, then Associate Professor in Residence, in the Department of Pharmacology, at the University of California, San Francisco. In the interim, he completed his doctorate at the Department of Pharmacology gaining his PhD in Pharmacology in 1965 from the University of California. This research took place in the laboratory of Prof. T.N. Burbridge examining the possibility that chlorpromazine inhibited the conjugation of bilirubin in the liver. The thesis was titled Inhibition of uridine diphosphoglucose dehydrogenase by a free radical formed from chlorpromazine.
In this period, in collaboration with Dr Paul Fasal, a Vienna-trained dermatologist, he followed up O’Byrne’s report in the International Journal of Leprosy that purported to show that hypothyroidism was beneficial to patients with leprosy. As a result of this work with methimazole in leprosy, Dr Levy became interested in developing an objective and quantitative technique for measuring the response of leprosy patients to chemotherapy.
The interest led to a project with Dr CC Shepard which involved treating leprosy patients in San Francisco, performing biopsies at intervals during treatment with dapsone, and air-expressing the biopsy-specimens to Atlanta. In Dr. Shepard’s laboratory, the M. leprae were extracted from the specimens and inoculated into mice. This was a collaboration that was to endure until Dr. Shepard’s death more than 20 years later. At this time, Dr. C.C. Shepard was screening drugs for activity against Mycobacterium leprae by “cultivating” the organisms in the mouse foot pad, and administering the drugs to the infected mice, in order to determine if the drugs could prevent multiplication of the organisms in the mice. He was also working intensively on development of the “solid ratio” – the determination of the proportion of viable M. leprae by careful examination under optimal microscopic conditions.
In the mid-1960s, President Lyndon B Johnson and the then prime minister of Japan established the U.S. – Japan Cooperative Medical Science Program. Dr Levy submitted an application for funds to establish a mouse foot pad laboratory in San Francisco, and was awarded a large grant. This became the Leprosy Research Unit at the San Francisco PHS Hospital, and Dr Levy became the Chief of the Leprosy Research Unit, at the Public Health Service Hospital, San Francisco, 1965-1976.
In the course of the next 11 years, the Leprosy Research Unit carried on activities in several areas. Primary was the mouse foot pad laboratory itself, in which important clinical trials were carried out, drugs were screened for activity against M. leprae, and both the M. leprae-infected mouse and the mouse foot pad technique itself were studied. In addition, the Leprosy Research Unit participated in clinical trials carried out in Cebu that were funded by the U.S. Leprosy Panel. Also, a number of graduate students and postdoctoral fellows carried out their research in the Unit. Finally, collaborations with other scientists in the San Francisco Bay Area, primarily at the Stanford Research Institute and the Palo Alto Medical Research Foundation, were undertaken.
After Dr Levy moved to Israel, he became involved, at Dr Sansarricq's invitation, with the development of THELEP which he chaired from its beginning in 1977 to 1984. Funds for his research at the Faculty of Medicine of the Hebrew University of Jerusalem were provided initially by the Canadian and Belgian members of ILEP with the help of Prof. Michel Lechat, and later THELEP, USAID, the French Follereau Foundation, and two binational research organizations – one U.S.-Israel, and the other Germany-Israel. The work carried out here was done primarily on M. marinum and M. lepraemurium.
After the Orlando Congress, Dr Levy assisted the Sasakawa Memorial Health Foundation (SMHF) reorganise research activities at the Sasakawa Research Building in Bangkok. He supervised the mouse foot pad laboratory and assumed responsibility for editing the proceedings of several workshops that had been organized by the SMHF. He continues to carry out research in collaboration with Prof. Patrick J. Brennan and Prof. Sang-Nae Cho.
Treatment Used/Researched:
Sulphones Dr Levy conducted extensive research into the metabolism of dapsone and also into dapsone resistance, using the foot pad model.
Research Institute(s) associated with:
Leprosy Research Unit, San Francisco, California, USA
The LRU was headed by Louis Levy, M.D., Ph.D. (1965 - 1976)
Some of Dr Levy's publications are as follows:
L Levy, P Fasal, JM Vogel. "The mechanism of the anti-leprosy action of methimazole: a preliminary report", Military Med 128 (1963): 987.
L Levy, LJ Higgins. "Dapsone assay based on Schiff base formation", Int J Leprosy 34 (1966): 411.
P Fasal, E Fasal, L Levy. "Leprosy prophylaxis", J Am Med Assoc 199 (1967): 905.
L Levy, P Fasal, LP Murray. "Morphology of Mycobacterium leprae in tissue sections", Arch Derm 95 (1967): 451.
L Levy, LP Murray, P Fasal. "The lack of effect of methimazole therapy in lepromatous leprosy. Reassessment by examination of bacterial morphology", Int J Leprosy 35 (1967): 149.
L Levy, LP Murray. "Analysis of a trial of dapsone vs. placebo in lepromatous leprosy", Int J Leprosy 35 (1967): 393.
L Levy. "The efficacy of sulfone therapy in leprosy", Int J Leprosy 35 (1967): 563.
CC Shepard, L Levy, P Fasal. The death of Mycobacterium leprae during treatment with 4,4'-diaminodiphenylsulfone (DDS). Initial rate in patients. Am J Trop Med Hyg 17(1968)769.
CC Shepard, L Levy, P Fasal. "The sensitivity to dapsone of Mycobacterium leprae from patients with and without previous treatment", AJTMH 18 (1969): 258.
L Levy. "The effect of several rates of freezing and thawing on the viability of Mycobacterium leprae", Cryobiol 6 (1969): 42.
JH Peters, SC Lin, L Levy. "A rapid qualitative spot test for the detection of dapsone in urine", Int J Leprosy 37 (1969): 46.
L Levy, LP Murray. "Uniformity of the solid ratio of Mycobacterium leprae from lesion to lesion. Int J Leprosy 37 (1969): 416.
L Levy, CC Shepard, LP Murray."A comparative study of mouse foot pad inoculation of skin biopsy specimens from patients with lepromatous leprosy in San Francisco and Atlanta", Int J Leprosy 38 (1970): 54.
L Levy. "Death of Mycobacterium leprae in mice, and the additional effect of dapsone administration", Proc Soc Exp Biol Med 135 (1970): 745.
L Levy, HP Randall. "A study of skin pigmentation by clofazimine", Int J Leprosy 38(404)1970.
RH Gelber, JH Peters, GR Gordon, AJ Glazko, L Levy. "The polymorphic acetylation of dapsone in man", Clin Pharmacol Therap 12 (1971): 225.
JT Biggs, L Levy." Binding of dapsone and monoacetyldapsone by human plasma proteins", Proc Soc Exp Biol Med 137 (1971): 692.
JH Peters, L Levy. "Dapsone acetylation in man: another example of polymorphic acetylation", Ann NY Acad Sci 179 (1971): 660.
L Levy. "The effect of freezing and storage at -60oC on the viability of Mycobacterium leprae", Crybiol 8 (1971): 574.
L Levy. "Prolongation of the lag phase of Mycobacterium leprae by dapsone", Proc Soc Exp Biol Med 139 (1972): 263.
MJ Evans, L Levy."Ultrastructural changes in cells of the mouse foot pad infected with Mycobacterium leprae", Infect Immun 5 (1972): 238.
L Levy, CC Shepard, P Fasal. "Clofazimine therapy of lepromatous leprosy caused by dapsone-resistant Mycobacterium leprae", Am J Trop Med Hyg 21 (1972): 315.
L Levy, JT Biggs, GR Gordon, JH Peters. "Disposition of the anti-leprosy drug, dapsone, in the mouse", Proc Soc Exp Biol Med 140 (1972): 937.
CC Shepard, L Levy, P Fasal. "The death rate of Mycobacterium leprae during treatment of lepromatous leprosy with acedapsone (DADDS)", Am J Trop Med Hyg 21 (1972): 440.
CC Shepard, L Levy, P Fasal. "Rapid bactericidal effect of rifampin on Mycobacterium leprae" Am J Trop Med Hyg 21 (1972): 446.
JH Peters, GR Gordon, DC Ghoul, JG Tolentino, GP Walsh, L Levy. "The disposition of the antileprotic drug dapsone (DDS) in Philippine subjects", Am J Trop Med Hyg 21(1972)450.
L Levy, N Moon. "Inhibition of the multiplication of Mycobacterium leprae by methimazole", Am Rev Resp Dis 106 (1972): 917.
MJ Evans, HE Newton, L Levy. "Early response of the mouse foot pad to Mycobacterium leprae", Infect Immun 7(1973)76.
RW Riley, L Levy. "Characteristics of the binding of dapsone and monoacetyldapsone by serum albumin", Proc Soc Exp Biol Med 142 (1973): 1168.
L Levy, P Fasal, NE Levan, RI Freedman. "Erythema nodosum leprosum", Lancet 2 (1973): 324.
H Ng, PL Jacobsen, L Levy. Analogy of Mycobacterium marinum disease to Mycobacterium leprae infection in foot pads of mice", Infect Immun 8 (1973): 860.
DJ Drutz, MJ Cline, L Levy." Leucocyte antimicrobial function in patients with leprosy", J Clin Invest 53 (1974): 380.
JH Peters, GR Gordon, L Levy, MA Storkan, RR Jacobson, CD Enna, WF Kirchheimer. "Metabolic disposition of dapsone in patients with dapsone-resistant leprosy", Am J Trop Med Hyg 23 (1974): 222.
CC Shepard, L Levy, P Fasal. "Further experience with the rapid bactericidal effect of rifampin on Mycobacterium leprae", Am J Trop Med Hyg 23 (1974): 1120.
L Levy, N Moon, LP Murray, SM O'Neill, LE Gustafson, MJ Evans. "Studies of the mouse foot pad technic for cultivation of Mycobacterium leprae 1. Fate of inoculated organisms", Int J Leprosy 42 (1974): 165.
L Levy. "Pharmacological studies of clofazimine", Am J Trop Med Hyg 23 (1974): 1097.
DJ Drutz, SM O'Neill, L Levy. "The viability of blood-borne Mycobacterium leprae", J Infect Dis 130 (1974): 288.
JL Krahenbuhl, L Levy, JS Remington. "Resistance to Mycobacterium leprae in mice infected with Toxoplasma gondii and Besnoitia jellisoni", Infect Immun 10 (1974): 1068.
RG Navalkar, PJ Patel, RR Dalvi, L Levy." Immune response to Mycobacterium leprae. Plaque-forming cells in mice", Infect Immun 10 (1974): 1302.
JH Peters, GR Gordon, JT Biggs, L Levy. "The disposition of dapsone and monoacetyldapsone in the dog" Proc Soc Exp Biol Med 148 (1975): 251.
L Levy, NM Ullmann. "Inhibition of multiplication of Mycobacterium leprae by several antithyroid drugs", Am Rev Resp Dis 111 (1975): 651.
CC Shepard, L Levy, P Fasal. "Rifampicin's rapid bactericidal action on M. leprae", Ain Shams Med J 25 (Suppl) (1974): 279.
L Levy. "Superinfection in mice previously infected with Mycobacterium leprae", Infect Immun 11 (1975): 1094.
L Levy, H Ng, MJ Evans, JL Krahenbuhl." Susceptibility of thymectomized and irradiated mice to challenge with several organisms, and the effect of dapsone on infection with Mycobacterium leprae", Infect Immun 11 (1975): 1122.
L Levy."The activity of chaulmoogra acids against Mycobacterium leprae", Am Rev Resp Dis 111 (1975): 703.
"Collaborative effort of the US Leprosy Panel (US-Japan Cooperative Medical Science Program) and the Leonard Wood Memorial. Rifampin therapy of lepromatous leprosy", Am J Trop Med Hyg 24 (1975): 475.
L Levy, LP Murray. "Studies of the mouse foot-pad technique for cultivation of Mycobacterium leprae. 2. The relationship between incubation period and generation time", Leprosy Rev 47 (1976): 13.
L Levy. "Studies of the mouse foot-pad technique for cultivation of Mycobacterium leprae. 3. Doubling time during logarithmic multiplication", Leprosy Rev 47 (1976): 103.
L Levy." Bactericidal action of dapsone against Mycobacterium leprae in mice", Antimicrob Ag Chemother 9 (1976): 614.
"Collaborative effort of the US Leprosy Panel (US-Japan Cooperative Medical Science Program) and the Leonard Wood Memorial. Spaced clofazimine therapy of lepromatous leprosy", Am J Trop Med Hyg 25 (1976): 437.AH Fieldsteel, L Levy." Dapsone chemotherapy of Mycobacterium leprae infection of the neonatally thymectomised Lewis rat", Am J Trop Med Hyg 25 (1976): 854.
L Levy." Activity of a thiadiazole on Mycobacterium leprae" Proc Soc Exp Biol Med 153 (1976): 34.
AH Fieldsteel, L Levy. "Neonatally thymectomized Lewis rats infected with Mycobacterium leprae: response to primary infection, secondary challenge, and large inocula", Infect Immun 14 (1976): 736.
"Committee on experimental chemotherapy. Experimental chemotherapy in leprosy", Bull WHO 53 (1976): 425.
L Levy, CC Shepard, P Fasal. "The bactericidal effect of rifampicin on M. leprae in man", Int J Leprosy 44 (1976): 183.
WM Krushat, KE Schilling, SA Edlavitch, L Levy. "Studies of the mouse foot-pad technique for cultivation of Mycobacterium leprae. 4. Statistical analysis of harvest data", Leprosy Rev 47 (1976): 275.
RH Gelber, L Levy. "The effect of dihydrofolate reductase inhibitors on Mycobacterium leprae in the mouse foot pad", Int J Leprosy 44 (1976): 124.
L Levy. "Treatment failure in leprosy", Int J Leprosy 44(1976)177.
TM Welch, L Levy. "Preliminary studies with the lymph node lymphocytes ofM. leprae infected mice", Int J Leprosy 44 (1976): 199.
JL Krahenbuhl, TM Welch, L Levy. "The presence of systemic and local activated macrophages in mice infected in the foot pad with Mycobacterium leprae and M. marinum", Int J Leprosy 44 (1976): 206.
L Levy, TC Merigan. "Inhibition of multiplication of Mycobacterium leprae by polyinosinic:polycytidylic acid", Antimicrob Ag Chemother 11 (1977): 122.
MJ Evans, L Levy." Failure of Mycobacterium leprae to incorporate 3H-thymidine administered in vivo", Leprosy Rev 48 (1977): 27.
"Collaborative effort of the US Leprosy Panel (US-Japan Cooperative Medical Science Program) and the Leonard Wood Memorial. A statistical analysis of two chemotherapy trials in lepromatous leprosy. The response to therapy as measured by mouse inoculation", Am J Trop Med Hyg 27 (1978): 1005.
"Collaborative effort of the US Leprosy Panel (US-Japan Cooperative Medical Science Program) and the Leonard Wood Memorial. A statistical analysis of two chemotherapy trials in lepromatous leprosy. II. Interactions among patient variables", Am J Trop Med Hyg 27 (1978): 1015.
TM Welch, RH Gelber, LP Murray, H Ng, SM O'Neill, L Levy. "Viability of Mycobacterium leprae after multiplication in mice", Infect Immun 30(1980): 325.
L Levy. "The THELEP program", Star 5 (1980): 39.
L Levy." Evolution of the modern chemotherapy of leprosy", Leprosy Rev Special Issue (1983): 69S.
"Subcommittee on clinical trials of the Chemotherapy of Leprosy (THELEP) Scientific Working Group of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. THELEP controlled clinical trials in lepromatous leprosy", Leprosy Rev 54 (1983): 167.
"Subcommittee on clinical trials of the Chemotherapy of Leprosy (THELEP) Scientific Working Group of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. Primary resistance to dapsone among untreated lepromatous patients in Bamako and Chingleput", Leprosy Rev 54 (1983): 177.
T Godal, L Levy. Chapter 45. Mycobacterium leprae, in The Mycobacteria: A Source Book. Eds GP Kubica, LG Wayne. Marcel Dekker. (1984): 598.
L Levy. The Kellersberger Memorial Lecture, 1984:" Chemotherapy of leprosy--a tool for leprosy control" Ethiopian Med J 23 (1985): 31.
CC Shepard, RJW Rees, L Levy, SR Pattyn, Ji Baohong, E de la Cruz." Susceptibility of strains of Mycobacterium leprae isolated prior to 1977 from patients with previously untreated lepromatous leprosy", Int J Leprosy 54 (1986): 11.
L Levy."Clofazimine-resistant M. leprae", Int J Leprosy 54 (1986): 137.
"Subcommittee on clinical trials of the Chemotherapy of Leprosy (THELEP) Scientific Working Group of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. Characteristics of patients in the THELEP trials of chemotherapy of leprosy in Bamako and Chingleput", Leprosy Rev 58 (1987): 7.
M Resnick, H Bercovier, F Aizer, N Mor, L Levy. Death of Mycobacterium lepraemurium in CBA, BALB/c and nude mice", Ann Microbiol Pasteur 138 (1987): 15.
"Subcommittee on clinical trials of the Chemotherapy of Leprosy (THELEP) Scientific Working Group of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. Primary dapsone-resistance in Bamako and Chingleput--final report", Leprosy Rev 58 (1987): 209.
H Bercovier, M Resnick, D Kornitzer, L Levy. "Rapid method for testing drug-susceptibility of Mycobacteria spp. and gram-positive bacteria using rhodamine 123 and fluorescein diacetate", J Microbiol Meth 7 (1987) 139.
"Subcommittee on clinical trials of the Chemotherapy of Leprosy (THELEP) Scientific Working Group of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. Persisting Mycobacterium leprae among THELEP trial patients in Bamako and Chingleput", Leprosy Rev 58 (1987): 325.
"Subcommittee on clinical trials of the Chemotherapy of Leprosy (THELEP) Scientific Working Group of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. The THELEP controlled clinical drug trials", Int J Leprosy 55 (1987): 864.
"Workshop on Experimental Chemotherapy", Ed. L Levy. Int J Leprosy 56 (1987).
B Ji, E de la Cruz, L Levy, SR Pattyn, RJW Rees. "Dapsone susceptibility of Mycobacterium leprae isolated before 1977", Int J Leprosy 56 (1988): 328.
"Subcommittee on clinical trials of the Chemotherapy of Leprosy (THELEP) Scientific Working Group of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. Characteristics of the multiplication of dapsone-resistant strains of Mycobacterium leprae in mice", Leprosy Rev 59 (1988): 5.
L Levy. Chapter 114. Leprosy. In Infectious Diseases, 4th Edition. Eds PD Hoeprich, MC Jordan. Harper & Row. (1989): 1013.
L Levy." Primum non nocere, the ethics of trials of leprosy chemotherapy", Lepr Rev 64 (1993): 185.
"Subcommittee on clinical trials of the chemotherapy of leprosy (THELEP) Scientific Working Group of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. Response to treatment by multi-drug regimens in the THELEP controlled clinical drug trials", Lepr Rev 67 (1996): 260.
B Ji, L Levy, J-H Grosset."Chemotherapy of leprosy: progress since the Orlando Congress, and prospects for the future", Int J Leprosy 64 (Supplement) (1996): S80.
"International Workshop on Leprosy Research", Ed. L Levy. Int J Leprosy 64 (Supplement) (1996): S1-S92
"Workshop on the Prevention of Leprosy", Ed. L Levy. Int J Leprosy 67 (Supplement) (1999): S1-S82.
The THELEP Controlled Clinical Trials in Lepromatous Leprosy. Ed. L Levy. World Health Organization, Geneva, 1999.
B Ji, L Levy. Chapter 38. Models of leprosy infection in mice. In Handbook of Animal Models of Infection, Academic Press, (1999): 337.
"Workshop on Leprosy Research at the New Millenium", Ed. L Levy. Leprosy Rev 71 (Supplement) (2000): S1-S192.
M Ngamying, P Varachit, P Phaknilrat, L Levy, PJ Brennan, S-N Cho. "Effects of vaccination with several mycobacterial proteins and lipoproteins on Mycobacterium leprae infection of the mouse", IJL 69 (2001): 43.