Abstract
Mycobacterium leprae cells extracted from the skin biopsies of 14 bacilliferous lepromatous patients were maintained in human-murine macrophage cultures for 3 weeks in the presence of [3H]thymidine and DDS (4,4'-diaminodiphenyl sulfone). All cultures except one containing freshly extracted viable bacilli showed significant incorporation of [3H]thymidine as compared to control cultures containing heat-killed bacilli of the corresponding strain. Six susceptible strains of M. leprae obtained from untreated, freshly diagnosed patients showed significant inhibition of the uptake of the radiolabel in the presence of 3 and 10 ng of DDS per ml per culture. Eight strains of M. leprae obtained from patients clinically suspected of DDS resistance were tested in a similar manner. These strains were also concurrently inoculated in the footpads of mice given orally 10(-2), 10(-3), and 10(-4) g of DDS per 100 g of body weight for 9 months. Concordant results were obtained by both methods: five strains were found to be resistant, one was susceptible, and one was partially resistant. Strain VIII did not incorporate [3H]thymidine in the macrophage cultures and proved to be resistant in the mouse footpad. The macrophage culture system provides a sensitive, rapid screening method for the early diagnosis of DDS resistance.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ambrose E. J., Antia N. H., Khonolkar S. R. Uptake of radioactive DOPA by M. leprae. Nature. 1974 Jun 28;249(460):854–855. doi: 10.1038/249854a0. [DOI] [PubMed] [Google Scholar]
- Ambrose E. J., Khanolkar S. R., Chulawalla R. G. A rapid test for bacillary resistance to dapsone. Lepr India. 1978 Apr;50(2):131–143. [PubMed] [Google Scholar]
- Desikan K. V. Viability of Mycobacterium leprae outside the human body. Lepr Rev. 1977 Dec;48(4):231–235. [PubMed] [Google Scholar]
- Drutz D. J., Cline M. J. Incorporation of tritiated thymidine by leprosy bacilli in cultures of human lepromatous macrophages. J Infect Dis. 1972 Apr;125(4):416–419. doi: 10.1093/infdis/125.4.416. [DOI] [PubMed] [Google Scholar]
- Ellard G. A., Gammon P. T., Rees R. J., Waters M. F. Studies on the determination of the minimal inhibitory concentration of 4,4'-diamino-diphenyl-sulphone (Dapsone, DDS) against Mycobacterium leprae. Lepr Rev. 1971 Jun;42(2):101–117. doi: 10.5935/0305-7518.19710013. [DOI] [PubMed] [Google Scholar]
- Girdhar B. K., Sreevatsa, Desikan K. V. Primary sulphone resistance. A preliminary report. Lepr India. 1978 Jul;50(3):352–355. [PubMed] [Google Scholar]
- Gorczynski R. M., Miller R. G., Phillips R. A. In vivo requirement for a radiation-resistant cells in the immune response to sheep erythrocytes. J Exp Med. 1971 Nov 1;134(5):1201–1221. doi: 10.1084/jem.134.5.1201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holmes I. B., Hilson G. R. The effect of rifampicin and dapsone on experimental Mycobacterium leprae infections: minimum inhibitory concentrations and bactericidal action. J Med Microbiol. 1972 May;5(2):251–261. doi: 10.1099/00222615-5-2-251. [DOI] [PubMed] [Google Scholar]
- Khanolkar S. R., Ambrose E. J., Chulawala R. G., Bapat C. V. Autoradiographic and metabolic studies of Mycobacterium leprae. Lepr Rev. 1978 Sep;49(3):187–198. [PubMed] [Google Scholar]
- Khanolkar S. R., Antia N. H. Autoradiographic studies of Mycobacterium leprae. Lepr Rev. 1976 Dec;47(4):267–273. [PubMed] [Google Scholar]
- Levy L., Peters J. H. Susceptibility of Mycobacterium leprae to dapsone as a determinant of patient response to acedapsone. Antimicrob Agents Chemother. 1976 Jan;9(1):102–112. doi: 10.1128/aac.9.1.102. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ozawa T., Shepard C. C., Karat A. B. Application of spectrophotofluorometric procedures to some problems in Mycobacterium leprae infections in mice and man treated with dapsone (DDS), diacetyl-DDS (DADDS), and di-formyl-DDS (DFD). Am J Trop Med Hyg. 1971 Mar;20(2):274–281. doi: 10.4269/ajtmh.1971.20.274. [DOI] [PubMed] [Google Scholar]
- PETTIT J. H., REES R. J. SULPHONE RESISTANCE IN LEPROSY. AN EXPERIMENTAL AND CLINICAL STUDY. Lancet. 1964 Sep 26;2(7361):673–674. doi: 10.1016/s0140-6736(64)92482-1. [DOI] [PubMed] [Google Scholar]
- Pearson J. M., Rees R. J., Waters M. F. Sulphone resistance in leprosy. A review of one hundred proven clinical cases. Lancet. 1975 Jul 12;2(7924):69–72. doi: 10.1016/s0140-6736(75)90508-5. [DOI] [PubMed] [Google Scholar]
- Peters J. H., Gordon G. R., Murray J. F., Jr, Fieldsteel A. H., Levy L. Minimal inhibitory concentration of dapsone for Mycobacterium leprae in rats. Antimicrob Agents Chemother. 1975 Nov;8(5):551–557. doi: 10.1128/aac.8.5.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peters J. H., Shepard C. C., Gordon G. R., Rojas A. V., Elizondo D. S. The incidence of DDS resistance in lepromatous patients in Costa Rica: their metabolic disposition of DDS. Int J Lepr Other Mycobact Dis. 1976 Jan-Jun;44(1-2):143–151. [PubMed] [Google Scholar]
- Prasad H. K., Nath I. Incorporation of 3H-thymidine in Mycobacterium leprae within differentiated human macrophages. J Med Microbiol. 1981 Aug;14(3):279–293. doi: 10.1099/00222615-14-3-279. [DOI] [PubMed] [Google Scholar]
- Rees R. J. Enhanced susceptibility of thymectomized and irradiated mice to infection with Mycobacterium leprae. Nature. 1966 Aug 6;211(5049):657–658. doi: 10.1038/211657a0. [DOI] [PubMed] [Google Scholar]
- Rees R. J. Leprosy. A preliminary review of the experimental evaluation of drugs for the treatment of leprosy. Trans R Soc Trop Med Hyg. 1967;61(4):581–595. doi: 10.1016/0035-9203(67)90111-3. [DOI] [PubMed] [Google Scholar]
- Ridley D. S., Hilson G. R. A logarithmic index of bacilli in biopsies. I. Method. Int J Lepr Other Mycobact Dis. 1967 Apr-Jun;35(2):184–186. [PubMed] [Google Scholar]
- Samuel D. R., Godal T., Myrvang B., Song Y. K. Behavior of Mycobacterium leprae in human macrophages in vitro. Infect Immun. 1973 Sep;8(3):446–449. doi: 10.1128/iai.8.3.446-449.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sathish M., Nath I. The uptake of 3H-thymidine in Mycobacterium leprae inoculated mouse macrophage cultures as a rapid indicator of bacillary viability. Factors influencing the specificity of the in vitro assay. Int J Lepr Other Mycobact Dis. 1981 Jun;49(2):187–193. [PubMed] [Google Scholar]
- Shepard C. C. A survey of the drugs with activity against M. leprae in mice. Int J Lepr Other Mycobact Dis. 1971 Apr-Jun;39(2):340–348. [PubMed] [Google Scholar]
- Shepard C. C., McRae D. H. A method for counting acid-fast bacteria. Int J Lepr Other Mycobact Dis. 1968 Jan-Mar;36(1):78–82. [PubMed] [Google Scholar]
- Shepard C. C., McRae D. H., Habas J. A. Sensitivity of Mycobacterium leprae to low levels of 4,4'-diaminodiphenyl sulfone. Proc Soc Exp Biol Med. 1966 Jul;122(3):893–896. doi: 10.3181/00379727-122-31282. [DOI] [PubMed] [Google Scholar]
- Talwar G. P., Krishnan A. D., Gupta P. D. Quantitative evaluation of the progress of intracellular infection in vitro: incorporation of 3H-thymidine into deoxyribonucleic acid by Mycobacterium leprae in cultivated blood monocytes. Infect Immun. 1974 Jan;9(1):187–191. doi: 10.1128/iai.9.1.187-191.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]