Skip to main content
SpringerLink
Log in

Neglected Tropical Bacterial Diseases

  • Chapter
  • First Online:
Book cover Communicable Diseases of the Developing World

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 29))

Abstract

Neglected tropical diseases (NTDs) belong to a diverse group of communicable diseases caused by pathogens including helminthes, protozoa, bacteria, and viruses. The NTDs prevail in tropical and subtropical conditions in 149 countries and affect billions of people, resulting in an economic burden of billions of dollars every year. The major neglected tropical bacterial diseases (NTBDs) are Leprosy, Buruli ulcer, and Trachoma. Leprosy and Buruli ulcer are caused by members of the Mycobacterium genus viz M. leprae and M. ulcerans and are responsible for the most severe medical impact in the tropics. Trachoma is the result of infection of the eye with Chlamydia trachomatis and it is responsible for the visual impairment of about 1.8 million people, of whom 0.5 million are irreversibly blind. In this chapter the above major NTBDs are discussed in terms of their epidemiology, pathogenic vector, metabolism, genomic and immunological analysis, classification, treatment, resistance, and vaccine development.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Abbreviations

BB:

Borderline borderline

BL:

Borderline lepromatous

BT:

Borderline tuberculoid

BU:

Buruli ulcer

CMI:

Cell-mediated immunity

DC:

Dendritic cell

DC-SIGN:

DC specific intercellular adhesion molecule-grabbing nonintegrin

DDS:

Dapsone

DF5HT:

Deoxyfructo-5-hydroxytryptamine

DHPS:

Dihydropteroate synthase

EB:

Elementary body

ENL:

Erythema nodosum leprosum

Hsp:

Heat shock protein

IL-12:

Ligand-associated interleukin 12

LL:

Lepromatous leprosy

MB:

Multibacillary leprosy

MDT:

Multidrug therapy

MHC:

Major histocompatibility complex

MOMP:

Major outer membrane protein

NK cells:

Natural killer cells

NTBD:

Neglected tropical bacterial disease

NTD:

Neglected tropical disease

ORF:

Open reading frame

PB:

Paucibacillary leprosy

PBMC:

Peripheral blood mononuclear cell

PGL:

Phenolic glycolipid

PmpD:

Polymorphic membrane protein D

PSSHE:

Persistent serpentine supravenous hyperpigmented eruption

RB:

Reticulate body

TCA:

Tricarboxylic acid

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TSC:

Thiosemicarbazone

TT:

Tuberculoid leprosy

WHO:

World Health Organization

References

  1. Fenwick A (2012) The global burden of neglected tropical diseases. Public Health 126:233–236

    Article  CAS  PubMed  Google Scholar 

  2. Lupi O, Madkan V, Tyring SK (2006) Tropical dermatology: bacterial tropical diseases. J Am Acad Dermatol 54:559–578

    Article  PubMed  Google Scholar 

  3. Browne SG (1985) The history of leprosy. In: Leprosy. Longman Group, Edinburgh, pp 1–14

    Google Scholar 

  4. Monot M, Honoré N, Garnier T, Araoz R, Coppée J-Y, Lacroix C, Sow S, Spencer JS, Truman RW, Williams DL (2005) On the origin of leprosy. Science 308:1040–1042

    Article  CAS  PubMed  Google Scholar 

  5. Trautman JR (1984) A brief history of Hansen’s disease. Bull N Y Acad Med 60:689

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Frank G (1991) Leprosy, racism, and public health: social policy in chronic disease control. ZACHARY GUSSOW. Am Ethnol 18:383–384

    Article  Google Scholar 

  7. Walker SL, Lockwood DNJ (2007) Leprosy. Clin Dermatol 25:165–172

    Article  PubMed  Google Scholar 

  8. Avula B, Khan SI, Tekwani BL, Dhammika Nanayakkara N, McChesney JD, Walker LA, Khan IA (2011) Analysis of primaquine and its metabolite carboxyprimaquine in biological samples: enantiomeric separation, method validation and quantification. Biomed Chromatogr 25:1010–1017

    Article  CAS  PubMed  Google Scholar 

  9. Hansen GA, Looft C (1895) Leprosy: in its clinical and pathological aspects. Am J Med Sci 110:586

    Article  Google Scholar 

  10. Meyers W (1995) Mycobacterial infections of the skin. In: Tropical pathology. Springer, Berlin, pp 291–377

    Chapter  Google Scholar 

  11. Guerrant RL, Walker DH, Weller PF (2011) Tropical infectious diseases: principles, pathogens and practice. Elsevier, Edinburgh

    Google Scholar 

  12. Hatta M, van Beers SM, Madjid B, Djumadi A, de Wit MY, Klatser PR (1995) Distribution and persistence of Mycobacterium leprae nasal carriage among a population in which leprosy is endemic in Indonesia. Trans R Soc Trop Med Hyg 89:381–385

    Article  CAS  PubMed  Google Scholar 

  13. Rees R, McDougall A (1977) Airborne infection with Mycobacterium leprae in mice. J Med Microbiol 10:63–68

    Article  CAS  PubMed  Google Scholar 

  14. Brandsma J, Yoder L, Macdonald M (2005) Leprosy acquired by inoculation from a knee injury. Lepr Rev 76:175–179

    CAS  PubMed  Google Scholar 

  15. Walsh G, Storrs E, Meyers W, Binford C (1977) Naturally acquired leprosy-like disease in the nine-banded armadillo (Dasypus novemcinctus): recent epizootiologic findings. J Reticuloendothel Soc 22:363–367

    CAS  PubMed  Google Scholar 

  16. Donham KJ, Leininger JR (1977) Spontaneous leprosy-like disease in a chimpanzee. J Infect Dis 136:132–136

    Article  CAS  PubMed  Google Scholar 

  17. Meyers WM, Gormus BJ, Walsh GP, Baskin GB, Hubbard GB (1991) Naturally acquired and experimental leprosy in nonhuman primates. Am J Trop Med Hyg 44:24–27

    Article  CAS  PubMed  Google Scholar 

  18. Wolf RH, Gormus BJ, Martin LN, Baskin GB, Walsh GP, Meyers WM, Binford CH (1985) Experimental leprosy in three species of monkeys. Science 227:529–531

    Article  CAS  PubMed  Google Scholar 

  19. Lumpkin LR, Cox GF, Wolf JE (1983) Leprosy in five armadillo handlers. J Am Acad Dermatol 9:899–903

    Article  PubMed  Google Scholar 

  20. West BC, Todd JR, Lary CH, Blake LA, Fowler ME, King JW (1988) Leprosy in six isolated residents of northern Louisiana: time-clustered cases in an essentially nonendemic area. Arch Intern Med 148:1987–1992

    Article  CAS  PubMed  Google Scholar 

  21. World Health Organization (2015) Global leprosy update, 2014: need for early case detection. Wkly Epidemiol Rec 90(36): 461–476

    Google Scholar 

  22. Rastogi N, Legrand E, Sola C (2001) The mycobacteria: an introduction to nomenclature and pathogenesis. Rev Sci Tech 20:21–54

    Article  CAS  PubMed  Google Scholar 

  23. Scollard DM, Truman RW, Ebenezer GJ (2015) Mechanisms of nerve injury in leprosy. Clin Dermatol 33:46–54

    Article  PubMed  Google Scholar 

  24. White C, Franco-Paredes C (2015) Leprosy in the 21st century. Clin Microbiol Rev 28:80–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Polycarpou A, Walker SL, Lockwood DN (2013) New findings in the pathogenesis of leprosy and implications for the management of leprosy. Curr Opin Infect Dis 26:413–419

    CAS  PubMed  Google Scholar 

  26. Truman RW, Krahenbuhl JL (2001) Viable M. leprae as a research reagent. Int J Lepr Other Mycobact Dis 69:1–12

    CAS  PubMed  Google Scholar 

  27. Ng V, Zanazzi G, Timpl R, Talts JF, Salzer JL, Brennan PJ, Rambukkana A (2000) Role of the cell wall phenolic glycolipid-1 in the peripheral nerve predilection of Mycobacterium leprae. Cell 103:511–524

    Article  CAS  PubMed  Google Scholar 

  28. Zu Bentrup KH, Miczak A, Swenson DL, Russell DG (1999) Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis. J Bacteriol 181:7161–7167

    Google Scholar 

  29. McKinney JD, Höner zu Bentrup K, Muñoz-Elías EJ, Miczak A, Chen B, Chan W-T, Swenson D, Sacchettini JC, Jacobs WR, Russell DG (2000) Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406:735–738

    Article  CAS  PubMed  Google Scholar 

  30. Cole S, Eiglmeier K, Parkhill J, James K, Thomson N, Wheeler P, Honore N, Garnier T, Churcher C, Harris D (2001) Massive gene decay in the leprosy bacillus. Nature 409:1007–1011

    Article  CAS  PubMed  Google Scholar 

  31. Wheeler PR (2003) Leprosy–clues about the biochemistry of Mycobacterium leprae and its host-dependency from the genome. World J Microbiol Biotechnol 19:1–16

    Article  CAS  Google Scholar 

  32. Eiglmeier K, Parkhill J, Honore N, Garnier T, Tekaia F, Telenti A, Klatser P, James KD, Thomson NR, Wheeler PR (2001) The decaying genome of Mycobacterium leprae. Lepr Rev 72:387–398

    CAS  PubMed  Google Scholar 

  33. Monot M, Honoré N, Garnier T, Zidane N, Sherafi D, Paniz-Mondolfi A, Matsuoka M, Taylor GM, Donoghue HD, Bouwman A (2009) Comparative genomic and phylogeographic analysis of Mycobacterium leprae. Nat Genet 41:1282–1289

    Article  CAS  PubMed  Google Scholar 

  34. Cole ST (1998) Comparative mycobacterial genomics. Curr Opin Microbiol 1:567–571

    Article  CAS  PubMed  Google Scholar 

  35. Wheeler PR (2001) The microbial physiologist’s guide to the leprosy genome. Lepr Rev 72:399–407

    CAS  PubMed  Google Scholar 

  36. Ribeiro-Rodrigues R (2012) Host response to M. leprae. Springer, Mailand

    Book  Google Scholar 

  37. Gulia A, Fried I, Massone C (2010) New insights in the pathogenesis and genetics of leprosy. F1000 Med Rep 2: 30. doi: 10.3410/M2-30

  38. Maeda Y, Gidoh M, Ishii N, Mukai C, Makino M (2003) Assessment of cell mediated immunogenicity of Mycobacterium leprae-derived antigens. Cell Immunol 222:69–77

    Article  CAS  PubMed  Google Scholar 

  39. Hashimoto K, Maeda Y, Kimura H, Suzuki K, Masuda A, Matsuoka M, Makino M (2002) Mycobacterium leprae infection in monocyte-derived dendritic cells and its influence on antigen-presenting function. Infect Immun 70:5167–5176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kimura H, Maeda Y, Takeshita F, Takaoka L, Matsuoka M, Makino M (2004) Upregulation of T‐cell‐stimulating activity of mycobacteria‐infected macrophages. Scand J Immunol 60:278–286

    Article  CAS  PubMed  Google Scholar 

  41. Sieling PA, Jullien D, Dahlem M, Tedder TF, Rea TH, Modlin RL, Porcelli SA (1999) CD1 expression by dendritic cells in human leprosy lesions: correlation with effective host immunity. J Immunol 162:1851–1858

    CAS  PubMed  Google Scholar 

  42. Gimenez M, GIGLI I, Tausk F (1989) Differential expression of Langerhans cells in the epidermis of patients with leprosy. Br J Dermatol 121:19–26

    Article  CAS  PubMed  Google Scholar 

  43. Krutzik SR, Ochoa MT, Sieling PA, Uematsu S, Ng YW, Legaspi A, Liu PT, Cole ST, Godowski PJ, Maeda Y (2003) Activation and regulation of toll-like receptors 2 and 1 in human leprosy. Nat Med 9:525–532

    Article  CAS  PubMed  Google Scholar 

  44. Massone C, Nunzi E, Ribeiro-Rodrigues R, Talhari C, Talhari S, Schettini APM, Parente JNT, Brunasso AM, Puntoni M, Clapasson A (2010) T regulatory cells and plasmocytoid dendritic cells in Hansen disease: a new insight into pathogenesis? Am J Dermatopathol 32:251–256

    Article  PubMed  Google Scholar 

  45. Schlesinger L (1993) Macrophage phagocytosis of virulent but not attenuated strains of Mycobacterium tuberculosis is mediated by mannose receptors in addition to complement receptors. J Immunol 150:2920–2930

    CAS  PubMed  Google Scholar 

  46. van Kooyk Y, Geijtenbeek TB (2003) DC-SIGN: escape mechanism for pathogens. Nat Rev Immunol 3:697–709

    Article  PubMed  CAS  Google Scholar 

  47. Kissenpfennig A, Aït-Yahia S, Clair-Moninot V, Stössel H, Badell E, Bordat Y, Pooley JL, Lang T, Prina E, Coste I (2005) Disruption of the langerin/CD207 gene abolishes Birbeck granules without a marked loss of Langerhans cell function. Mol Cell Biol 25:88–99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Brightbill HD, Libraty DH, Krutzik SR, Yang R-B, Belisle JT, Bleharski JR, Maitland M, Norgard MV, Plevy SE, Smale ST (1999) Host defense mechanisms triggered by microbial lipoproteins through Toll-like receptors. Science 285:732–736

    Article  CAS  PubMed  Google Scholar 

  49. Underhill DM, Ozinsky A, Smith KD, Aderem A (1999) Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc Natl Acad Sci 96:14459–14463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Schlesinger LS, Horwitz MA (1991) Phenolic glycolipid-1 of Mycobacterium leprae binds complement component C3 in serum and mediates phagocytosis by human monocytes. J Exp Med 174:1031–1038

    Article  CAS  PubMed  Google Scholar 

  51. Modlin RL, Melancon-Kaplan J, Young S, Pirmez C, Kino H, Convit J, Rea TH, Bloom BR (1988) Learning from lesions: patterns of tissue inflammation in leprosy. Proc Natl Acad Sci 85:1213–1217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Modlin RL, Hofman FM, Taylor CR, Rea TH (1983) T lymphocyte subsets in the skin lesions of patients with leprosy. J Am Acad Dermatol 8:182–189

    Article  CAS  PubMed  Google Scholar 

  53. Sieling P, Chatterjee D, Porcelli S, Prigozy T, Mazzaccaro R, Soriano T, Bloom B, Brenner M, Kronenberg M, Brennan P et al (1995) CD1-restricted T cell recognition of microbial lipoglycan antigens. Science 269:227–230

    Article  CAS  PubMed  Google Scholar 

  54. Hancock GE, Molloy A, Kale AB, Kiessling R, Becx-Bleumink M, Cohn ZA, Kaplan G (1991) In vivo administration of low-dose human interleukin-2 induces lymphokine-activated killer cells for enhanced cytolysis in vitro. Cell Immunol 132:277–284

    Article  CAS  PubMed  Google Scholar 

  55. Chiplunkar S, De Libero G, Kaufmann S (1986) Mycobacterium leprae-specific Lyt-2+ T lymphocytes with cytolytic activity. Infect Immun 54:793–797

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Kaleab B, Ottenoff T, Converse P, Halapi E, Tadesse G, Rottenberg M, Kiessling R (1990) Mycobacterial‐induced cytotoxic T cells as well as nonspecific killer cells derived from healthy individuals and leprosy patients. Eur J Immunol 20:2651–2659

    Article  CAS  PubMed  Google Scholar 

  57. Shi L, Kraut R, Aebersold R, Greenberg A (1992) A natural killer cell granule protein that induces DNA fragmentation and apoptosis. J Exp Med 175:553–566

    Article  CAS  PubMed  Google Scholar 

  58. Sibley LD, Franzblau SG, Krahenbuhl JL (1987) Intracellular fate of Mycobacterium leprae in normal and activated mouse macrophages. Infect Immun 55:680–685

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Sibley LD, Krahenbuhl JL (1988) Induction of unresponsiveness to gamma interferon in macrophages infected with Mycobacterium leprae. Infect Immun 56:1912–1919

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Chiplunkar S, Deshmukh M, Samson P, Butlin R, Bhatki W, Chulawalla R, Deo M, Gangal S (1990) Natural killer-cell-mediated and antibody-dependent cellular cytotoxicity in leprosy. Int J Lepr Other Mycobact Dis 58:334–341

    CAS  PubMed  Google Scholar 

  61. Steinhoff U, Wand-Württenberger A, Bremerich A, Kaufmann S (1991) Mycobacterium leprae renders Schwann cells and mononuclear phagocytes susceptible or resistant to killer cells. Infect Immun 59:684–688

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Ramasesh N, Adams L, Franzblau S, Krahenbuhl J (1991) Effects of activated macrophages on Mycobacterium leprae. Infect Immun 59:2864–2869

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357

    CAS  PubMed  Google Scholar 

  64. Salgame P, Abrams JS, Clayberger C, Goldstein H, Convit J, Modlin RL, Bloom BR (1991) Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science 254:279–282

    Article  CAS  PubMed  Google Scholar 

  65. Ridley D (1987) Skin biopsy in leprosy. Histological interpretation and clinical application, 2nd edn. Ciba, Basle, p 63

    Google Scholar 

  66. World Health Organization (1998) WHO model prescribing information: drugs used in leprosy. World Health Organization, Geneva

    Google Scholar 

  67. Shimoji Y, Ng V, Matsumura K, Fischetti VA, Rambukkana A (1999) A 21-kDa surface protein of Mycobacterium leprae binds peripheral nerve laminin-2 and mediates Schwann cell invasion. Proc Natl Acad Sci 96:9857–9862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Rambukkana A (2001) Molecular basis for the peripheral nerve predilection of Mycobacterium leprae. Curr Opin Microbiol 4:21–27

    Article  CAS  PubMed  Google Scholar 

  69. Schlesinger L, Horwitz M (1991) Phagocytosis of Mycobacterium leprae by human monocyte-derived macrophages is mediated by complement receptors CR1 (CD35), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) and IFN-gamma activation inhibits complement receptor function and phagocytosis of this bacterium. J Immunol 147:1983–1994

    CAS  PubMed  Google Scholar 

  70. Schlesinger LS, Kaufman TM, Iyer S, Hull SR, Marchiando LK (1996) Differences in mannose receptor-mediated uptake of lipoarabinomannan from virulent and attenuated strains of Mycobacterium tuberculosis by human macrophages. J Immunol 157:4568–4575

    CAS  PubMed  Google Scholar 

  71. Knight JC, Keating BJ, Kwiatkowski DP (2004) Allele-specific repression of lymphotoxin-α by activated B cell factor-1. Nat Genet 36:394–399

    Article  CAS  PubMed  Google Scholar 

  72. Hagge DA, Robinson SO, Scollard D, McCormick G, Williams DL (2002) A new model for studying the effects of Mycobacterium leprae on Schwann cell and neuron interactions. J Infect Dis 186:1283–1296

    Article  CAS  PubMed  Google Scholar 

  73. Job CK (1989) Nerve damage in leprosy. Int J Lepr Other Mycobact Dis 57:532–539

    CAS  PubMed  Google Scholar 

  74. Scollard DM (2008) The biology of nerve injury in leprosy. Lepr Rev 79:242–253

    PubMed  Google Scholar 

  75. Spierings E, de Boer T, Wieles B, Adams LB, Marani E, Ottenhoff TH (2001) Mycobacterium leprae-specific, HLA class II-restricted killing of human Schwann cells by CD4+ Th1 cells: a novel immunopathogenic mechanism of nerve damage in leprosy. J Immunol 166:5883–5888

    Article  CAS  PubMed  Google Scholar 

  76. Oliveira RB, Ochoa MT, Sieling PA, Rea TH, Rambukkana A, Sarno EN, Modlin RL (2003) Expression of toll-like receptor 2 on human Schwann cells: a mechanism of nerve damage in leprosy. Infect Immun 71:1427–1433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Harboe M, Aseffa A, Leekassa R (2005) Challenges presented by nerve damage in leprosy. Lepr Rev 76:5–13

    PubMed  Google Scholar 

  78. Save M, Shetty V, Shetty K, Antia N (2004) Alterations in neurofilament protein (s) in human leprous nerves: morphology, immunohistochemistry and Western immunoblot correlative study. Neuropathol Appl Neurobiol 30:635–650

    Article  CAS  PubMed  Google Scholar 

  79. Lee H, Jo E-K, Choi S-Y, Oh SB, Park K, Kim JS, Lee SJ (2006) Necrotic neuronal cells induce inflammatory Schwann cell activation via TLR2 and TLR3: implication in Wallerian degeneration. Biochem Biophys Res Commun 350:742–747

    Article  CAS  PubMed  Google Scholar 

  80. Khanolkar‐Young S, Rayment N, Brickell P, Katz D, Vinayakumar S, Colston M, Lockwood D (1995) Tumour necrosis factor‐alpha (TNF‐α) synthesis is associated with the skin and peripheral nerve pathology of leprosy reversal reactions. Clin Exp Immunol 99:196–202

    Article  PubMed  PubMed Central  Google Scholar 

  81. Lockwood D, Suneetha L, Sagili KD, Chaduvula MV, Mohammed I, van Brakel W, Smith W, Nicholls P, Suneetha S (2011) Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort. PLoS Negl Trop Dis 5:e1327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Shetty V, Antia N (1988) Nerve damage in leprosy. Int J Lepr Other Mycobact Dis 56:619

    CAS  PubMed  Google Scholar 

  83. Reibel F, Cambau E, Aubry A (2015) Update on the epidemiology, diagnosis, and treatment of leprosy. Med Mal Infect 45:383–393

    Article  CAS  PubMed  Google Scholar 

  84. Skinsnes O (1972) Origin of chaulmoogra oil--another version. Int J Lepr Other Mycobact Dis 40:172

    CAS  PubMed  Google Scholar 

  85. Jacobsen PL, Levy L (1973) Mechanism by which hydnocarpic acid inhibits mycobacterial multiplication. Antimicrob Agents Chemother 3:373–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Bennett BH, Parker DL, Robson M (2008) Leprosy: steps along the journey of eradication. Public Health Rep 123:198

    Article  PubMed  PubMed Central  Google Scholar 

  87. Singh R (2002) Synthetic drugs. Mittal, New Delhi

    Google Scholar 

  88. Lowe J (1950) Treatment of leprosy with diamino-diphenyl sulphone by mouth. Lancet 255:145–150

    Article  Google Scholar 

  89. Wozel G, Barth J (1988) Current aspects of modes of action of dapsone. Int J Dermatol 27:547–552

    Article  CAS  PubMed  Google Scholar 

  90. Dallas WS, Gowen J, Ray PH, Cox M, Dev I (1992) Cloning, sequencing, and enhanced expression of the dihydropteroate synthase gene of Escherichia coli MC4100. J Bacteriol 174:5961–5970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Williams DL, Spring L, Harris E, Roche P, Gillis TP (2000) Dihydropteroate synthase of Mycobacterium leprae and dapsone resistance. Antimicrob Agents Chemother 44:1530–1537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Kettle AJ, Winterbourn CC (1991) Mechanism of inhibition of myeloperoxidase by anti-inflammatory drugs. Biochem Pharmacol 41:1485–1492

    Article  CAS  PubMed  Google Scholar 

  93. Uetrecht J (1994) Myeloperoxidase as a generator of drug free radicals. Biochem Soc Symp 61:163–170

    Article  Google Scholar 

  94. Diaz‐Ruiz A, Zavala C, Montes S, Ortiz‐Plata A, Salgado‐Ceballos H, Orozco‐Suarez S, Nava‐Ruiz C, Pérez‐Neri I, Perez‐Severiano F, Ríos C (2008) Antioxidant, antiinflammatory and antiapoptotic effects of dapsone in a model of brain ischemia/reperfusion in rats. J Neurosci Res 86:3410–3419

    Article  PubMed  CAS  Google Scholar 

  95. Bukirwa H, Garner P, Critchley J (2004) Chlorproguanil-dapsone for treating uncomplicated malaria. Cochrane Database Syst Rev CD004387 doi: 10.1002/14651858.CD004387.pub2

  96. Pettit J, Rees R (1964) Sulphone resistance in leprosy: an experimental and clinical study. Lancet 284:673–674

    Article  Google Scholar 

  97. Pearson T, Rees R, Waters M (1975) Sulphone resistance in leprosy: a review of one hundred proven clinical cases. Lancet 306:69–72

    Article  Google Scholar 

  98. Perlman D (1977) Structure-activity relationships among the semisynthetic antibiotics. Academic, New York

    Google Scholar 

  99. Corcoran JW, Hahn FE (1975) Mechanism of action of antimicrobial and antitumor agents. Springer, New York

    Book  Google Scholar 

  100. Rees R, Pearson J, Waters M (1970) Experimental and clinical studies on rifampicin in treatment of leprosy. Br Med J 1:89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Levy L, Shepard C, Fasal P (1975) The bactericidal effect of rifampicin on M. leprae in man: a) single doses of 600, 900 and 1200 mg; and b) daily doses of 300 mg. Int J Lepr Other Mycobact Dis 44:183–187

    Google Scholar 

  102. Calvori C, Frontali L, Leoni L, Tecce G (1965) Effect of rifamycin on protein synthesis. Nature 207:417–418

    Article  CAS  PubMed  Google Scholar 

  103. Jin DJ, Gross CA (1988) Mapping and sequencing of mutations in the Escherichia coli rpoB gene that lead to rifampicin resistance. J Mol Biol 202:45–58

    Article  CAS  PubMed  Google Scholar 

  104. Campbell EA, Korzheva N, Mustaev A, Murakami K, Nair S, Goldfarb A, Darst SA (2001) Structural mechanism for rifampicin inhibition of bacterial RNA polymerase. Cell 104:901–912

    Article  CAS  PubMed  Google Scholar 

  105. Feklistov A, Mekler V, Jiang Q, Westblade LF, Irschik H, Jansen R, Mustaev A, Darst SA, Ebright RH (2008) Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center. Proc Natl Acad Sci 105:14820–14825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Hastings R, Richard V, Jacobson R (1984) Ansamycin activity against rifampicin-resistant Mycobacterium leprae. Lancet 323:1130

    Article  Google Scholar 

  107. Pattyn S, Saerens E (1977) Activity of three new rifamycin derivates on the experimental infection by Mycobacterium leprae. Ann Soc Belg Med Trop 57:169–173

    CAS  PubMed  Google Scholar 

  108. Pattyn S (1987) Rifabutin and rifapentine compared with rifampin against Mycobacterium leprae in mice. Antimicrob Agents Chemother 31:134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Ji B, Chen J, Lu X, Wang S, Ni G, Hou Y, Zhou D, Tang Q (1986) Antimycobacterial activities of two newer ansamycins, R-76-1 and DL 473. Int J Lepr Other Mycobact Dis 54:563–577

    CAS  PubMed  Google Scholar 

  110. Tomioka H, Saito H, Hidaka T (1993) In vivo antileprosy activity of the newly synthesized benzoxazinorifamycin, KRM-1648. Int J Lepr Other Mycobact Dis 61:255–258

    CAS  PubMed  Google Scholar 

  111. Saito H, Tomioka H, Sato K, Dekio S (1994) Therapeutic efficacy of benzoxazinorifamycin, KRM-1648, in combination with other antimicrobials against Mycobacterium leprae infection induced in nude mice. Int J Lepr Other Mycobact Dis 62:43

    CAS  PubMed  Google Scholar 

  112. Hasanoor Reja A, Biswas N, Biswas S, Lavania M, Chaitanya VS, Banerjee S, Maha Patra P, Gupta UD, Patra PK, Sengupta U (2015) Report of rpoB mutation in clinically suspected cases of drug resistant leprosy: a study from Eastern India. Indian J Dermatol Venereol Leprol 81:155

    Article  PubMed  Google Scholar 

  113. Williams DL, Gillis TP (2012) Drug-resistant leprosy: monitoring and current status. Lepr Rev 83:269

    PubMed  Google Scholar 

  114. Saxena M, Bhunia SS, Saxena AK (2012) Docking studies of novel pyrazinopyridoindoles class of antihistamines with the homology modelled H1-receptor. SAR QSAR Environ Res 23:311

    Article  CAS  PubMed  Google Scholar 

  115. Bhunia SS, Roy KK, Saxena AK (2011) Profiling the structural determinants for the selectivity of representative factor-Xa and thrombin inhibitors using combined ligand-based and structure-based approaches. J Chem Inf Model 51:1966

    Article  CAS  PubMed  Google Scholar 

  116. Bhunia SS, Singh S, Saxena S, Saxena AK (2015) Pharmacophore modeling, docking and molecular dynamics studies on caspase-3 activators binding at β-tubulin site. Curr Comput Aided Drug Des 11:72

    Article  CAS  PubMed  Google Scholar 

  117. Azad CS, Bhunia SS, Krishna A, Shukla PK, Saxena AK (2015) Novel glycoconjugate of 8‐fluoro norfloxacin derivatives as gentamicin‐resistant Staphylococcus aureus inhibitors: synthesis and molecular modelling studies. Chem Biol Drug Des 86:440

    Article  CAS  PubMed  Google Scholar 

  118. Saxena M, Bhunia SS, Saxena AK (2015) Molecular modelling studies on 2-substituted octahydropyrazinopyridoindoles for histamine H2 receptor antagonism. SAR QSAR Environ Res 26:739

    Article  CAS  PubMed  Google Scholar 

  119. Nisha J, Shanthi V (2015) Computational simulation techniques to understand rifampicin resistance mutation (S425L) of rpoB in M. leprae. J Cell Biochem 116:1278–1285

    Article  CAS  PubMed  Google Scholar 

  120. Van Rensburg C, Gatner E, Imkamp F, Anderson R (1982) Effects of clofazimine alone or combined with dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy. Antimicrob Agents Chemother 21:693–697

    Article  PubMed  PubMed Central  Google Scholar 

  121. Anderson R, Smit MJ (1993) Clofazimine and B669 inhibit the proliferative responses and Na+, K+-adenosine triphosphatase activity of human lymphocytes by a lysophospholipid-dependent mechanism. Biochem Pharmacol 46:2029–2038

    Article  CAS  PubMed  Google Scholar 

  122. Mohd A, Parwaz Khan AA, Bano S, Siddiqi K (2011) Interaction of clofazimine with divalent metal ions: a fluorescence quenching study. J Dispers Sci Technol 32:1465–1469

    Article  CAS  Google Scholar 

  123. Kashyap A, Sehgal VN, Sahu A, Saha K (1992) Anti-leprosy drugs inhibit the complement-mediated solubilization of pre-formed immune complexes in vitro. Int J Immunopharmacol 14:269–273

    Article  CAS  PubMed  Google Scholar 

  124. Faouzi M, Starkus J, Penner R (2015) State‐dependent blocking mechanism of Kv1. 3 channels by the antimycobacterial drug clofazimine. Br J Pharmacol 172:5161–5173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Chuaprapaisilp T, Piamphongsant T (1978) Treatment of pustular psoriasis with clofazimine. Br J Dermatol 99:303–305

    Article  CAS  PubMed  Google Scholar 

  126. Podmore P, Burrows D (1986) Clofazimine: an effective treatment for Melkersson‐Rosenthal syndrome or Miescher’s cheilitis. Clin Exp Dermatol 11:173–178

    Article  CAS  PubMed  Google Scholar 

  127. Kelleher D, O’Brien S, Weir D (1982) Preliminary trial of clofazimine in chronic inflammatory bowel-disease. Gut 23:A449–A450

    Google Scholar 

  128. Bellera CL, Balcazar DE, Vanrell MC, Casassa AF, Palestro PH, Gavernet L, Labriola CA, Gálvez J, Bruno-Blanch LE, Romano PS (2015) Computer-guided drug repurposing: identification of trypanocidal activity of clofazimine, benidipine and saquinavir. Eur J Med Chem 93:338–348

    Article  CAS  PubMed  Google Scholar 

  129. Koval A, Vlasov P, Shichkova P, Khunderyakova S, Markov Y, Panchenko J, Volodina A, Kondrashov F, Katanaev V (2014) Anti-leprosy drug clofazimine inhibits growth of triple-negative breast cancer cells via inhibition of canonical Wnt signaling. Biochem Pharmacol 87:571–578

    Article  CAS  PubMed  Google Scholar 

  130. Arbiser JL, Moschella SL (1995) Clofazimine: a review of its medical uses and mechanisms of action. J Am Acad Dermatol 32:241–247

    Article  CAS  PubMed  Google Scholar 

  131. Yoon GS, Sud S, Keswani RK, Baik J, Standiford TJ, Stringer KA, Rosania GR (2015) Phagocytosed clofazimine biocrystals can modulate innate immune signaling by inhibiting TNFα and boosting IL-1RA secretion. Mol Pharm 12:2517–2527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Fukutomi Y, Maeda Y, Makino M (2011) Apoptosis-inducing activity of clofazimine in macrophages. Antimicrob Agents Chemother 55:4000–4005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Pourgholami MH, Lu Y, Wang L, Stephens RW, Morris DL (2004) Regression of Novikoff rat hepatocellular carcinoma following locoregional administration of a novel formulation of clofazimine in lipiodol. Cancer Lett 207:37–47

    Article  CAS  PubMed  Google Scholar 

  134. Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer TW, Spitzer GM et al (2011) Identification of novel functional inhibitors of acid sphingomyelinase. PLoS One 6:e23852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Franzblau S, O'sullivan J (1988) Structure-activity relationships of selected phenazines against Mycobacterium leprae in vitro. Antimicrob Agents Chemother 32:1583–1585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Franzblau SG, White KE, O'Sullivan JF (1989) Structure-activity relationships of tetramethylpiperidine-substituted phenazines against Mycobacterium leprae in vitro. Antimicrob Agents Chemother 33:2004–2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Van Landingham RM, Walker LL, O'Sullivan JF, Shinnick TM (1993) Activity of phenazine analogs against Mycobacterium leprae infections in mice. Int J Lepr Other Mycobact Dis 61:406

    PubMed  Google Scholar 

  138. Walker SL, Withington SG, Lockwood DNJ (2014) Leprosy. In: Farrar J, Hotez PJ, Junghanss T, Kang G, Lalloo D, White N (eds) Manson’s tropical diseases, 23rd edn. Elsevier Saunders, Philadelphia, pp 506–518

    Google Scholar 

  139. Saunderson PR (2015) Drug-resistant M. leprae. Clin Dermatol. doi:10.1016/j.clindermatol.2015.1010.1019

    Article  PubMed  Google Scholar 

  140. Andries K, Villellas C, Coeck N, Thys K, Gevers T, Vranckx L, Lounis N, de Jong BC, Koul A (2014) Acquired resistance of Mycobacterium tuberculosis to bedaquiline. PLoS One 9:e102135

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Hartkoorn RC, Uplekar S, Cole ST (2014) Cross-resistance between clofazimine and bedaquiline through upregulation of MmpL5 in Mycobacterium tuberculosis. Antimicrob Agents Chemother 58:2979–2981

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Zhang S, Chen J, Cui P, Shi W, Zhang W, Zhang Y (2015) Identification of novel mutations associated with clofazimine resistance in Mycobacterium tuberculosis. J Antimicrob Chemother 70:2507–2510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Franzblau SG, White KE (1990) Comparative in vitro activities of 20 fluoroquinolones against Mycobacterium leprae. Antimicrob Agents Chemother 34:229–231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Guelpa-Lauras C-C, Perani EG, Giroir A-M, Grosset JH (1987) Activities of pefloxacin and ciprofloxacin against Mycobacterium leprae in the mouse. Liver 1:17–28

    Google Scholar 

  145. Franzblau SG, Parrilla MLR, Chan GP (1993) Sparfloxacin is more bactericidal than ofloxacin against Mycobacterium leprae in mice. Int J Lepr Other Mycobact Dis 61:66

    CAS  PubMed  Google Scholar 

  146. Chan GP, Garcia-Ignacio BY, Chavez VE, Livelo J, Jimenez C, Parrilla M, Franzblau S (1994) Clinical trial of sparfloxacin for lepromatous leprosy. Antimicrob Agents Chemother 38:61–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Pardillo FEF, Burgos J, Fajardo TT, Cruz ED, Abalos RM, Paredes RMD, Andaya CES, Gelber RH (2008) Powerful bactericidal activity of moxifloxacin in human leprosy. Antimicrob Agents Chemother 52:3113–3117

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  148. Dhople AM, Namba K (2003) In-vitro activity of sitafloxacin (DU-6859a), either singly or in combination with rifampin analogs, against Mycobacterium leprae. J Infect Chemother 9:12–15

    Article  CAS  PubMed  Google Scholar 

  149. Keating GM (2011) Sitafloxacin. Drugs 71:731–744

    Article  CAS  PubMed  Google Scholar 

  150. Dhople AM, Ibanez MA (1995) The in-vitro activities of novel benzoxazinorifamycins against Mycobacterium leprae. J Antimicrob Chemother 35:463–471

    Article  CAS  PubMed  Google Scholar 

  151. Gelber R, Iranmanesh A, Murray L, Siu P, Tsang M (1992) Activities of various quinolone antibiotics against Mycobacterium leprae in infected mice. Antimicrob Agents Chemother 36:2544–2547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Aldred KJ, Kerns RJ, Osheroff N (2014) Mechanism of quinolone action and resistance. Biochemistry 53:1565–1574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Suto MJ, Domagala JM, Roland GE, Mailloux GB, Cohen MA (1992) Fluoroquinolones: relationships between structural variations, mammalian cell cytotoxicity and antimicrobial activity. J Med Chem 35:4745–4750

    Article  CAS  PubMed  Google Scholar 

  154. Owens RC, Ambrose PG (2005) Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis 41:S144–S157

    Article  CAS  PubMed  Google Scholar 

  155. Sarro A, Sarro G (2001) Adverse reactions to fluoroquinolones. An overview on mechanistic aspects. Curr Med Chem 8:371–384

    Article  PubMed  Google Scholar 

  156. FDA (2015) Joint Meeting of the Antimicrobial Drugs Advisory Committee (AMDAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM), 5 November 2015. www.fda.gov. Retrieved Dec 2015

  157. Cambau E, Sougakoff W, Jarlier V (1994) Amplification and nucleotide sequence of the quinolone resistance-determining region in the gyrA gene of mycobacteria. FEMS Microbiol Lett 116:49–54

    Article  CAS  PubMed  Google Scholar 

  158. Takiff HE, Salazar L, Guerrero C, Philipp W, Huang WM, Kreiswirth B, Cole ST, Jacobs WR, Telenti A (1994) Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations. Antimicrob Agents Chemother 38:773–780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Redin G (1966) Antibacterial activity in mice of minocycline, a new tetracycline. Antimicrob Agents Chemother 6:371

    CAS  PubMed  Google Scholar 

  160. Gelber RH (1987) Activity of minocycline in Mycobacterium leprae-infected mice. J Infect Dis 156:236–239

    Article  CAS  PubMed  Google Scholar 

  161. Ji B, Sow S, Perani E, Lienhardt C, Diderot V, Grosset J (1998) Bactericidal activity of a single-dose combination of ofloxacin plus minocycline, with or without rifampin, against Mycobacterium leprae in mice and in lepromatous patients. Antimicrob Agents Chemother 42:1115–1120

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Ji B, Jamet P, Perani EG, Bobin P, Grosset JH (1993) Powerful bactericidal activities of clarithromycin and minocycline against Mycobacterium leprae in lepromatous leprosy. J Infect Dis 168:188–190

    Article  CAS  PubMed  Google Scholar 

  163. Taylor DE, Chau A (1996) Tetracycline resistance mediated by ribosomal protection. Antimicrob Agents Chemother 40:1

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Regen F, Hildebrand M, Le Bret N, Herzog I, Heuser I, Hellmann‐Regen J (2015) Inhibition of retinoic acid catabolism by minocycline: evidence for a novel mode of action? Exp Dermatol 24:473–476

    Article  CAS  PubMed  Google Scholar 

  165. Sadowski T, Steinmeyer J (2001) Minocycline inhibits the production of inducible nitric oxide synthase in articular chondrocytes. J Rheumatol 28:336–340

    CAS  PubMed  Google Scholar 

  166. Chaudhry IB, Hallak J, Husain N, Minhas F, Stirling J, Richardson P, Dursun S, Dunn G, Deakin B (2012) Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment. J Psychopharmacol 26:1185–1193

    Article  PubMed  CAS  Google Scholar 

  167. Giuliani F, Hader W, Yong VW (2005) Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction. J Leukoc Biol 78:135–143

    Article  CAS  PubMed  Google Scholar 

  168. SAKIA UN (2015) Persistent serpentine supravenous hyperpigmented eruption in lepromatous leprosy after minocycline. Lepr Rev 86:191–194

    PubMed  Google Scholar 

  169. Speer BS, Shoemaker NB, Salyers AA (1992) Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance. Clin Microbiol Rev 5:387–399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Gelber RH (1995) Successful treatment of a lepromatous patient with clarithromycin. Int J Lepr Other Mycobact Dis 63:113

    CAS  PubMed  Google Scholar 

  171. Sturgill MG, Rapp RP (1992) Clarithromycin: review of a new macrolide antibiotic with improved microbiologic spectrum and favorable pharmacokinetic and adverse effect profiles. Ann Pharmacother 26:1099–1108

    Article  CAS  PubMed  Google Scholar 

  172. Rapp RP, McCraney SA, Goodman NL, Shaddick DJ (1994) New macrolide antibiotics: usefulness in infections caused by mycobacteria other than Mycobacterium tuberculosis. Ann Pharmacother 28:1255–1263

    Article  CAS  PubMed  Google Scholar 

  173. Vester B, Douthwaite S (2001) Macrolide resistance conferred by base substitutions in 23S rRNA. Antimicrob Agents Chemother 45:1–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Meier A, Heifets L, Wallace RJ, Zhang Y, Brown BA, Sander P, Bottger EC (1996) Molecular mechanisms of clarithromycin resistance in Mycobacterium avium: observation of multiple 238 rDNA mutations in a clonal population. J Infect Dis 174:354–360

    Article  CAS  PubMed  Google Scholar 

  175. You E-Y, Kang TJ, Kim S-K, Lee S-B, Chae G-T (2005) Mutations in genes related to drug resistance in Mycobacterium leprae isolates from leprosy patients in Korea. J Infect 50:6–11

    Article  PubMed  Google Scholar 

  176. Gidoh M (1999) [The control leprous peripheral neuropathy and chemotherapy]. Nihon Hansenbyo Gakkai Zasshi 68:83–86

    Article  CAS  PubMed  Google Scholar 

  177. Illarramendi X, de Oliveira MLWR, Sales AM, da Costa Nery JA, Sarno EN (2013) Considerations on clinical trials of leprosy treatment: need of novel drug combinations. Clin Invest 3:617–635

    Article  CAS  Google Scholar 

  178. Franzblau SG, Biswas AN, Harris EB (1992) Fusidic acid is highly active against extracellular and intracellular Mycobacterium leprae. Antimicrob Agents Chemother 36:92–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Franzblau SG, Chan GP, Garcia-Ignacio BG, Chavez VE, Livelo JB, Jimenez CL, Parrilla M, Calvo RF, Williams DL, Gillis TP (1994) Clinical trial of fusidic acid for lepromatous leprosy. Antimicrob Agents Chemother 38:1651–1654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Baker D, Beddell C, Champness J, Goodford P, Norrington F, Smith D, Stammers D (1981) The binding of trimethoprim to bacterial dihydrofolate reductase. FEBS Lett 126:49–52

    Article  CAS  PubMed  Google Scholar 

  181. Seydel J, Rosenfeld M, Sathish M, Wiese M, Schaper K-J, Hachtel G, Haller R, Kansy M, Dhople A (1986) Strategies in the development of new drugs and drug combinations against leprosy, demonstrated on the example of folate and gyrase inhibitors. Lepr Rev 57:235–253

    PubMed  Google Scholar 

  182. Seydel JK, Wiese M, Walter R, Kansy M, Schaper KJ, Sethi N, Chandra S, Dhople AM, Saxena AK (1994) In: Sushil Kumar, Sen AK, Dutta GP, Sharma RN (eds) Tropical diseases molecular biology and control strategies. Publication & Information Directorate, New Delhi, p 214

    Google Scholar 

  183. Dhople AM (1999) In vitro activity of epiroprim, a dihydrofolate reductase inhibitor, singly and in combination with brodimoprim and dapsone, against Mycobacterium leprae. Int J Antimicrob Agents 12:319–323

    Article  CAS  PubMed  Google Scholar 

  184. Seydel J (1993) In vitro and in vivo results of brodimoprim and analogues alone and in combination against E. coli and mycobacteria. J Chemother 5:422–429

    CAS  PubMed  Google Scholar 

  185. Dhople AM (2002) In vivo activity of epiroprim, a dihydrofolate reductase inhibitor, singly and in combination with dapsone, against Mycobacterium leprae. Int J Antimicrob Agents 19:71–74

    Article  CAS  PubMed  Google Scholar 

  186. Gaugas J (1967) Antimicrobial therapy of experimental human leprosy (Myco. leprae) infection in the mouse foot pad. Lepr Rev 38:225–230

    CAS  PubMed  Google Scholar 

  187. Baker RJ (1990) The need for new drugs in the treatment and control of leprosy. Int J Lepr Other Mycobact Dis 58:78–97

    CAS  PubMed  Google Scholar 

  188. Schaper K-J, Seydel J, Rosenfeld M, Kazda J (1986) Development of inhibitors of mycobacterial ribonucleotide reductase. Lepr Rev 57:254–264

    PubMed  Google Scholar 

  189. Mester L, Szabados L, Mester M, Yadav N (1980) Maillard type carbonyl-amine reactions in vivo and their physiological effects. Prog Food Nutr Sci 5:295–314

    Google Scholar 

  190. Antia N, Upleker M, Ambrose E, Mahadevan P, Mester L (1988) Effect of deoxyfructoserotonin (DFS) on lepromatous leprosy. Lancet 331:619–622

    Article  Google Scholar 

  191. Ambrose E, Antia N, Birdi T, Mahadevan P, Mester L, Mistry N, Mukherjee R, Shetty V (1985) The action of deoxyfructose serotonin on intracellular bacilli and on host response in leprosy. Lepr Rev 56:199–208

    CAS  PubMed  Google Scholar 

  192. Mester de Parajd L, Balakrishnan S, Saint-Andre P, Mester de Parajd M (1981) Deoxyfructo-serotonin: a new drug with anti-leprosy activity. Ann Microbiol 133:427–432

    Google Scholar 

  193. Faget G, Erickson P (1946) Use of streptomycin in the treatment of leprosy. Int J Lepr 15:146–153

    Google Scholar 

  194. DREISBACH J, Cochrane R (1958) A study of the effect of streptohydrazid on lepromatous leprosy over a period of about three years. Lepr Rev 29:136–142

    CAS  PubMed  Google Scholar 

  195. Gelber R, Gibson J (1979) Killing potential of various aminoglycoside antibiotics for Mycobacterium-leprae. Int J Lepr Other Mycobact Dis 47:684–685

    Google Scholar 

  196. Gelber R, Henika P, Gibson J (1984) The bactericidal activity of various aminoglycoside antibiotics against Mycobacterium leprae in mice. Lepr Rev 55:341–347

    CAS  PubMed  Google Scholar 

  197. Gelber RH (1987) Further studies of the killing of M. leprae by aminoglycosides: reduced dosage and frequency of administration. Int J Lepr Other Mycobact Dis 55:78–82

    CAS  PubMed  Google Scholar 

  198. Ebenezer G, Norman G, Joseph G, Daniel S, Job C (2001) Drug resistant-Mycobacterium leprae--results of mouse footpad studies from a laboratory in South India. Indian J Lepr 74:301–312

    Google Scholar 

  199. Honoré N, Roche PW, Grosset JH, Cole ST (2001) A method for rapid detection of rifampicin-resistant isolates of Mycobacterium leprae. Lepr Rev 72:441–448

    PubMed  Google Scholar 

  200. Musser JM (1995) Antimicrobial agent resistance in mycobacteria: molecular genetic insights. Clin Microbiol Rev 8:496–514

    CAS  PubMed  PubMed Central  Google Scholar 

  201. Sampaio LH, Stefani MM, Oliveira RM, Sousa AL, Ireton GC, Reed SG, Duthie MS (2011) Immunologically reactive M. leprae antigens with relevance to diagnosis and vaccine development. BMC Infect Dis 11:26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Stefani MM, Guerra JG, Sousa AL, Costa MB, Oliveira ML, Martelli CT, Scollard DM (2009) Potential plasma markers of type 1 and type 2 leprosy reactions: a preliminary report. BMC Infect Dis 9:75

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  203. Zodpey S, Bansod B, Shrikhande S, Maldhure B, Kulkarni S (1999) Protective effect of Bacillus Calmette Guerin (BCG) against leprosy: a population-based case-control study in Nagpur, India. Lepr Rev 70:287–294

    CAS  PubMed  Google Scholar 

  204. Zodpey S, Ambadekar N, Thakur A (2005) Effectiveness of Bacillus Calmette Guerin (BCG) vaccination in the prevention of leprosy: a population-based case-control study in Yavatmal District, India. Public Health 119:209–216

    Article  CAS  PubMed  Google Scholar 

  205. Rodrigues LC, Pereira SM, Cunha SS, Genser B, Ichihara MY, de Brito SC, Hijjar MA, Cruz AA, Sant'Anna C, Bierrenbach AL (2005) Effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: the BCG-REVAC cluster-randomised trial. Lancet 366:1290–1295

    Article  PubMed  Google Scholar 

  206. Nakanaga K, Yotsu RR, Hoshino Y, Suzuki K, Makino M, Ishii N (2013) Buruli ulcer and mycolactone-producing mycobacteria. Jpn J Infect Dis 66:83–88

    Article  PubMed  Google Scholar 

  207. Cook AR (1897) Mengo hospital notes. Makerere Medical School Library, Kampala

    Google Scholar 

  208. MacCallum P, Tolhurst JC, Buckle G, Sissons H (1948) A new mycobacterial infection in man. J Pathol Bacteriol 60:93–122

    Article  CAS  PubMed  Google Scholar 

  209. Clancey J, Dodge O, Lunn H, Oduori M (1961) Mycobacterial skin ulcers in Uganda. Lancet 278:951–954

    Article  Google Scholar 

  210. Wansbrough-Jones M, Phillips R (2006) Buruli ulcer: emerging from obscurity. Lancet 367:1849–1858

    Article  PubMed  Google Scholar 

  211. WHO (2008) Buruli ulcer: progress report: 2004–2008. Wkly Epidemiol Rec 83:144–154

    Google Scholar 

  212. Aujoulat I, Johnson C, Zinsou C, Guédénon A, Portaels F (2003) Psychosocial aspects of health seeking behaviours of patients with Buruli ulcer in Southern Benin. Trop Med Int Health 8:750–759

    Article  PubMed  Google Scholar 

  213. Debacker M, Aguiar J, Steunou C, Zinsou C, Meyers WM, Guédénon A, Scott JT, Dramaix M, Portaels F (2004) Mycobacterium ulcerans disease (Buruli ulcer) in rural hospital, Southern Benin, 1997-2001. Emerg Infect Dis 10:1391–1398

    Article  PubMed  PubMed Central  Google Scholar 

  214. Moran M, Guzman J, Ropars A-L, McDonald A, Jameson N, Omune B, Ryan S, Wu L (2009) Neglected disease research and development: how much are we really spending. PLoS Med 6:e1000030

    Article  PubMed Central  Google Scholar 

  215. Johnson P, Azuolas J, Lavender CJ, Wishart E, Stinear TP, Hayman JA, Brown L, Jenkin GA, Fyfe J (2007) Mycobacterium ulcerans in mosquitoes captured during outbreak of Buruli ulcer, Southeastern Australia. Emerg Infect Dis 13:1653–1660

    Article  PubMed  PubMed Central  Google Scholar 

  216. Portaels F, Elsen P, Guimaraes-Peres A, Fonteyne P-A, Meyers WM (1999) Insects in the transmission of Mycobacterium ulcerans infection. Lancet 353:986

    Article  CAS  PubMed  Google Scholar 

  217. Marsollier L, Robert R, Aubry J, Saint André J-P, Kouakou H, Legras P, Manceau A-L, Mahaza C, Carbonnelle B (2002) Aquatic insects as a vector for Mycobacterium ulcerans. Appl Environ Microbiol 68:4623–4628

    Article  PubMed  PubMed Central  Google Scholar 

  218. Portaels F, Meyers WM, Ablordey A, Castro AG, Chemlal K, de Rijk P, Elsen P, Fissette K, Fraga AG, Lee R (2008) First cultivation and characterization of Mycobacterium ulcerans from the environment. PLoS Negl Trop Dis 2:e178

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  219. The Uganda Buruli Group (1971) Epidemiology of Mycobacterium ulcerans infection (Buruli ulcer) at Kinyara, Uganda. Trans R Soc Trop Med Hyg 65:763–775

    Article  Google Scholar 

  220. Trubiano JA, Lavender CJ, Fyfe J, Bittmann S, Johnson P (2013) The incubation period of Buruli ulcer (Mycobacterium ulcerans infection). PLoS Negl Trop Dis 7:e2463

    Article  PubMed  PubMed Central  Google Scholar 

  221. Carson C, Lavender CJ, Handasyde KA, O'Brien CR, Hewitt N, Johnson PD, Fyfe JA (2014) Potential wildlife sentinels for monitoring the endemic spread of human Buruli ulcer in South-East Australia. PLoS Negl Trop Dis 8:e2668

    Article  PubMed  PubMed Central  Google Scholar 

  222. O'Brien CR, Handasyde KA, Hibble J, Lavender CJ, Legione AR, McCowan C, Globan M, Mitchell AT, McCracken HE, Johnson PD (2014) Clinical, microbiological and pathological findings of Mycobacterium ulcerans infection in three Australian Possum species. PLoS Negl Trop Dis 8:e2666

    Article  PubMed  PubMed Central  Google Scholar 

  223. Huang GKL, Johnson PD (2014) Epidemiology and management of Buruli ulcer. Expert Rev Anti Infect Ther 12:855–865

    Article  CAS  PubMed  Google Scholar 

  224. Junghanss T, Johnson RC, Pluschke G (2014) Mycobacterium ulcerans disease. In: Farrar J, Hotez PJ, Junghanss T, Kang G, Lalloo D, White N (eds) Manson’s tropical diseases, 23rd edn.Elsevier Saunders, Philadelphia, pp 519–531

    Google Scholar 

  225. WHO (2015) Buruli ulcer (Mycobacterium ulcerans infection) fact sheet N° 199, World Health Organization, Geneva. http://www.who.int/mediacentre/factsheets/fs199/en/

  226. Portaels F, Johnson P, Meyers WM (2001) Buruli ulcer: diagnosis of Mycobacterium ulcerans disease. World Health Organization, Geneva. https://extranet.who.int/iris/restricted/handle/10665/67000. Accessed December 2015

  227. Merritt RW, Walker ED, Small PL, Wallace JR, Johnson PD, Benbow ME, Boakye DA (2010) Ecology and transmission of Buruli ulcer disease: a systematic review. PLoS Negl Trop Dis 4:e911

    Article  PubMed  PubMed Central  Google Scholar 

  228. Stienstra Y, Van Der Graaf W, Te Meerman G, The T, De Leij L, Van der Werf T (2001) Susceptibility to development of Mycobacterium ulcerans disease: review of possible risk factors. Trop Med Int Health 6:554–562

    Article  CAS  PubMed  Google Scholar 

  229. Meyers WM, Shelly WM, Connor DH, Meyers EK (1974) Human Mycobacterium ulcerans infections developing at sites of trauma to skin. Am J Trop Med Hyg 23:919–923

    Article  CAS  PubMed  Google Scholar 

  230. Portaels F, Chemlal K, Elsen P, Johnson P, Hayman J, Hibble J, Kirkwood R, Meyers W (2001) Mycobacterium ulcerans in wild animals. Rev Sci Tech 20:252–264

    Article  CAS  PubMed  Google Scholar 

  231. Stinear TP, Seemann T, Pidot S, Frigui W, Reysset G, Garnier T, Meurice G, Simon D, Bouchier C, Ma L (2007) Reductive evolution and niche adaptation inferred from the genome of Mycobacterium ulcerans, the causative agent of Buruli ulcer. Genome Res 17:192–200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Daffé M, Varnerot A, Lévy-Frébault VV (1992) The phenolic mycoside of Mycobacterium ulcerans: structure and taxonomic implications. J Gen Microbiol 138:131–137

    Article  PubMed  Google Scholar 

  233. Stinear TP, Seemann T, Harrison PF, Jenkin GA, Davies JK, Johnson PD, Abdellah Z, Arrowsmith C, Chillingworth T, Churcher C (2008) Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis. Genome Res 18:729–741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Stinear TP, Mve-Obiang A, Small PL, Frigui W, Pryor MJ, Brosch R, Jenkin GA, Johnson PD, Davies JK, Lee RE (2004) Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans. Proc Natl Acad Sci USA 101:1345–1349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. George KM, Chatterjee D, Gunawardana G, Welty D, Hayman J, Lee R, Small P (1999) Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence. Science 283:854–857

    Article  CAS  PubMed  Google Scholar 

  236. George KM, Pascopella L, Welty DM, Small P (2000) A Mycobacterium ulcerans toxin, mycolactone, causes apoptosis in guinea pig ulcers and tissue culture cells. Infect Immun 68:877–883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Eddyani M, Fraga AG, Schmitt F, Uwizeye C, Fissette K, Johnson C, Aguiar J, Sopoh G, Barogui Y, Meyers WM (2009) Fine-needle aspiration, an efficient sampling technique for bacteriological diagnosis of nonulcerative Buruli ulcer. J Clin Microbiol 47:1700–1704

    Article  PubMed  PubMed Central  Google Scholar 

  238. Tian J, Bryk R, Itoh M, Suematsu M, Nathan C (2005) Variant tricarboxylic acid cycle in Mycobacterium tuberculosis: identification of α-ketoglutarate decarboxylase. Proc Natl Acad Sci USA 102:10670–10675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. Muñoz-Elías EJ, McKinney JD (2005) Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence. Nat Med 11:638–644

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  240. Brosch R, Pym AS, Gordon SV, Cole ST (2001) The evolution of mycobacterial pathogenicity: clues from comparative genomics. Trends Microbiol 9:452–458

    Article  CAS  PubMed  Google Scholar 

  241. Portevin D, de Sousa-D'Auria C, Houssin C, Grimaldi C, Chami M, Daffé M, Guilhot C (2004) A polyketide synthase catalyzes the last condensation step of mycolic acid biosynthesis in mycobacteria and related organisms. Proc Natl Acad Sci 101:314–319

    Article  CAS  PubMed  Google Scholar 

  242. Daffe M, Laneelle M, Lacave C (1991) Structure and stereochemistry of mycolic acids of Mycobacterium marinum and Mycobacterium ulcerans. Res Microbiol 142:397–403

    Article  CAS  PubMed  Google Scholar 

  243. Daffe M, Laneelle M, Roussel J, Asselineau C (1983) Specific lipids from Mycobacterium ulcerans. Ann Microbiol 135:191–201

    Google Scholar 

  244. Onwueme KC, Vos CJ, Zurita J, Soll CE, Quadri LE (2005) Identification of phthiodiolone ketoreductase, an enzyme required for production of mycobacterial diacyl phthiocerol virulence factors. J Bacteriol 187:4760–4766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. Reed MB, Domenech P, Manca C, Su H, Barczak AK, Kreiswirth BN, Kaplan G, Barry CE (2004) A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response. Nature 431:84–87

    Article  CAS  PubMed  Google Scholar 

  246. Rohdich F, Bacher A, Eisenreich W (2004) Perspectives in anti-infective drug design. The late steps in the biosynthesis of the universal terpenoid precursors, isopentenyl diphosphate and dimethylallyl diphosphate. Bioorg Chem 32:292–308

    Article  CAS  PubMed  Google Scholar 

  247. Yip MJ, Porter JL, Fyfe JA, Lavender CJ, Portaels F, Rhodes M, Kator H, Colorni A, Jenkin GA, Stinear T (2007) Evolution of Mycobacterium ulcerans and other mycolactone-producing mycobacteria from a common Mycobacterium marinum progenitor. J Bacteriol 189:2021–2029

    Article  CAS  PubMed  Google Scholar 

  248. Demangel C, Stinear TP, Cole ST (2009) Buruli ulcer: reductive evolution enhances pathogenicity of Mycobacterium ulcerans. Nat Rev Microbiol 7:50–60

    Article  CAS  PubMed  Google Scholar 

  249. Abdallah AM, van Pittius NCG, Champion PAD, Cox J, Luirink J, Vandenbroucke-Grauls CM, Appelmelk BJ, Bitter W (2007) Type VII secretion—mycobacteria show the way. Nat Rev Microbiol 5:883–891

    Article  CAS  PubMed  Google Scholar 

  250. Brodin P, Rosenkrands I, Andersen P, Cole ST, Brosch R (2004) ESAT-6 proteins: protective antigens and virulence factors? Trends Microbiol 12:500–508

    Article  CAS  PubMed  Google Scholar 

  251. Mishra KC, De Chastellier C, Narayana Y, Bifani P, Brown AK, Besra GS, Katoch VM, Joshi B, Balaji KN, Kremer L (2008) Functional role of the PE domain and immunogenicity of the Mycobacterium tuberculosis triacylglycerol hydrolase LipY. Infect Immun 76:127–140

    Article  CAS  PubMed  Google Scholar 

  252. Fortune S, Jaeger A, Sarracino D, Chase M, Sassetti C, Sherman D, Bloom B, Rubin E (2005) Mutually dependent secretion of proteins required for mycobacterial virulence. Proc Natl Acad Sci USA 102:10676–10681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. Huber CA, Ruf M-T, Pluschke G, Käser M (2008) Independent loss of immunogenic proteins in Mycobacterium ulcerans suggests immune evasion. Clin Vaccine Immunol 15:598–606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. Hong H, Demangel C, Pidot SJ, Leadlay PF, Stinear T (2008) Mycolactones: immunosuppressive and cytotoxic polyketides produced by aquatic mycobacteria. Nat Prod Rep 25:447–454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  255. Mve-Obiang A, Lee RE, Portaels F, Small P (2003) Heterogeneity of mycolactones produced by clinical isolates of Mycobacterium ulcerans: implications for virulence. Infect Immun 71:774–783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  256. Oswald E, Nougayrède J-P, Taieb F, Sugai M (2005) Bacterial toxins that modulate host cell-cycle progression. Curr Opin Microbiol 8:83–91

    Article  CAS  PubMed  Google Scholar 

  257. Simmonds RE, Lali FV, Smallie T, Small PL, Foxwell BM (2009) Mycolactone inhibits monocyte cytokine production by a posttranscriptional mechanism. J Immunol 182:2194–2202

    Article  CAS  PubMed  Google Scholar 

  258. Walsh DS, Meyers WM, Portaels F, Lane JE, Mongkolsirichaikul D, Hussem K, Gosi P, Myint KSA (2005) High rates of apoptosis in human Mycobacterium ulcerans culture-positive Buruli ulcer skin lesions. Am J Trop Med Hyg 73:410–415

    Article  PubMed  Google Scholar 

  259. Kishi Y (2011) Chemistry of mycolactones, the causative toxins of Buruli ulcer. Proc Natl Acad Sci 108:6703–6708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  260. Stinear TP, Pryor MJ, Porter JL, Cole ST (2005) Functional analysis and annotation of the virulence plasmid pMUM001 from Mycobacterium ulcerans. Microbiology 151:683–692

    Article  CAS  PubMed  Google Scholar 

  261. Goto M, Nakanaga K, Aung T, Hamada T, Yamada N, Nomoto M, Kitajima S, Ishii N, Yonezawa S, Saito H (2006) Nerve damage in Mycobacterium ulcerans-infected mice: probable cause of painlessness in Buruli ulcer. Am J Pathol 168:805–811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  262. En J, Goto M, Nakanaga K, Higashi M, Ishii N, Saito H, Yonezawa S, Hamada H, Small PL (2008) Mycolactone is responsible for the painlessness of Mycobacterium ulcerans infection (Buruli ulcer) in a murine study. Infect Immun 76:2002–2007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  263. Marion E, Song O-R, Christophe T, Babonneau J, Fenistein D, Eyer J, Letournel F, Henrion D, Clere N, Paille V (2014) Mycobacterial toxin induces analgesia in Buruli ulcer by targeting the angiotensin pathways. Cell 157:1565–1576

    Article  CAS  PubMed  Google Scholar 

  264. Guenin-Macé L, Veyron-Churlet R, Thoulouze M-I, Romet-Lemonne G, Hong H, Leadlay PF, Danckaert A, Ruf M-T, Mostowy S, Zurzolo C (2013) Mycolactone activation of Wiskott-Aldrich syndrome proteins underpins Buruli ulcer formation. J Clin Invest 123:1501–1502

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  265. Zimmermann R, Eyrisch S, Ahmad M, Helms V (2011) Protein translocation across the ER membrane. Biochim Biophys Acta Biomembr 1808:912–924

    Article  CAS  Google Scholar 

  266. Sarfo FS, Phillips R, Wansbrough‐Jones M, Simmonds RE (2015) Recent advances: role of mycolactone in the pathogenesis and monitoring of Mycobacterium ulcerans infection/Buruli ulcer disease. Cell Microbiol. doi:10.1111/cmi.12547

    Article  PubMed Central  Google Scholar 

  267. Scherr N, Gersbach P, Dangy J-P, Bomio C, Li J, Altmann K-H, Pluschke G (2013) Structure-activity relationship studies on the macrolide exotoxin mycolactone of Mycobacterium ulcerans. PLoS Negl Trop Dis 7:e2143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  268. Adusumilli S, Mve‐Obiang A, Sparer T, Meyers W, Hayman J, Small PLC (2005) Mycobacterium ulcerans toxic macrolide, mycolactone modulates the host immune response and cellular location of M. ulcerans in vitro and in vivo. Cell Microbiol 7:1295–1304

    Article  CAS  PubMed  Google Scholar 

  269. Schütte D, Um-Boock A, Mensah-Quainoo E, Itin P, Schmid P, Pluschke G (2007) Development of highly organized lymphoid structures in Buruli ulcer lesions after treatment with rifampicin and streptomycin. PLoS Negl Trop Dis 1:e2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  270. Torrado E, Fraga AG, Castro AG, Stragier P, Meyers WM, Portaels F, Silva MT, Pedrosa J (2007) Evidence for an intramacrophage growth phase of Mycobacterium ulcerans. Infect Immun 75:977–987

    Article  CAS  PubMed  Google Scholar 

  271. Torrado E, Fraga AG, Logarinho E, Martins TG, Carmona JA, Gama JB, Carvalho MA, Proença F, Castro AG, Pedrosa J (2010) IFN-γ–dependent activation of macrophages during experimental infections by Mycobacterium ulcerans is impaired by the toxin mycolactone. J Immunol 184:947–955

    Article  CAS  PubMed  Google Scholar 

  272. Hall BS, Hill K, McKenna M, Ogbechi J, High S, Willis AE, Simmonds RE (2014) The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER. PLoS Pathog 10:e1004061

    Article  PubMed  PubMed Central  Google Scholar 

  273. Coutanceau E, Decalf J, Martino A, Babon A, Winter N, Cole ST, Albert ML, Demangel C (2007) Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin mycolactone. J Exp Med 204:1395–1403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  274. Boulkroun S, Guenin-Macé L, Thoulouze M-I, Monot M, Merckx A, Langsley G, Bismuth G, Di Bartolo V, Demangel C (2010) Mycolactone suppresses T cell responsiveness by altering both early signaling and posttranslational events. J Immunol 184:1436–1444

    Article  CAS  PubMed  Google Scholar 

  275. Phillips R, Sarfo FS, Guenin-Macé L, Decalf J, Wansbrough-Jones M, Albert ML, Demangel C (2009) Immunosuppressive signature of cutaneous Mycobacterium ulcerans infection in the peripheral blood of patients with Buruli ulcer disease. J Infect Dis 200:1675–1684

    Article  CAS  PubMed  Google Scholar 

  276. Guenin-Macé L, Carrette F, Asperti-Boursin F, Le Bon A, Caleechurn L, Di Bartolo V, Fontanet A, Bismuth G, Demangel C (2011) Mycolactone impairs T cell homing by suppressing microRNA control of L-selectin expression. Proc Natl Acad Sci 108:12833–12838

    Article  PubMed  PubMed Central  Google Scholar 

  277. Ham O, Lee S-Y, Lee CY, Park J-H, Lee J, Seo H-H, Cha M-J, Choi E, Kim S, Hwang K-C (2015) Let-7b suppresses apoptosis and autophagy of human mesenchymal stem cells transplanted into ischemia/reperfusion injured heart 7by targeting caspase-3. Stem Cell Res Ther 6:1–11

    Article  CAS  Google Scholar 

  278. En J, Ishii N, Goto M (2011) Role of mycolactone in the nerve damage of Buruli ulcer (Mycobacterium ulcerans infection). Nihon Hansenbyo Gakkai Zasshi 80:5–10

    Article  PubMed  Google Scholar 

  279. World Health Organization (2012) Treatment of Mycobacterium ulcerans disease (Buruli ulcer): guidance for health workers. World Health Organization, Geneva. http://www.who.int/buruli/information/antibiotics/en

  280. Debacker M, Aguiar J, Steunou C, Zinsou C, Meyers WM, Portaels F (2005) Buruli ulcer recurrence, Benin. Emerg Infect Dis 11:584–589

    Article  PubMed  PubMed Central  Google Scholar 

  281. Van der Werf TS, Van der Graaf WT, Tappero JW, Asiedu K (1999) Mycobacterium ulcerans infection. Lancet 354:1013–1018

    Article  PubMed  Google Scholar 

  282. Teelken M, Stienstra Y, Ellen D, Quarshie E, Klutse E, van der Graaf W, van der Werf TS (2003) Buruli ulcer: differences in treatment outcome between two centres in Ghana. Acta Trop 88:51–56

    Article  CAS  PubMed  Google Scholar 

  283. O’Brien DP, Walton A, Hughes AJ, Friedman ND, McDonald A, Callan P, Rhadon R, Holten I, Athan E (2013) Risk factors for recurrent Mycobacterium ulcerans disease after exclusive surgical treatment in an Australian cohort. Med J Aust 198:436–439

    Article  PubMed  Google Scholar 

  284. Thangaraj H, Adjei O, Allen B, Portaels F, Evans M, Banerjee D, Wansbrough-Jones M (2000) In vitro activity of ciprofloxacin, sparfloxacin, ofloxacin, amikacin and rifampicin against Ghanaian isolates of Mycobacterium ulcerans. J Antimicrob Chemother 45:231–233

    Article  CAS  PubMed  Google Scholar 

  285. Saito H, Ishii N (2001) Antibacterial activities of new fluoroquinolones against Mycobacterium ulcerans. J Antimicrob Chemother 47:30

    Google Scholar 

  286. O'Brien DP, McDonald A, Callan P, Robson M, Friedman ND, Hughes A, Holten I, Walton A, Athan E (2012) Successful outcomes with oral fluoroquinolones combined with rifampicin in the treatment of Mycobacterium ulcerans: an observational cohort study. PLoS Negl Trop Dis 6:e1473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  287. Friedman ND, Athan E, Hughes AJ, Khajehnoori M, McDonald A, Callan P, Rahdon R, O’Brien DP (2013) Mycobacterium ulcerans disease: experience with primary oral medical therapy in an Australian cohort. PLoS Negl Trop Dis 7:e2315

    Article  PubMed  PubMed Central  Google Scholar 

  288. O'Brien DP, Athan E, Hughes A, Johnson PD (2008) Successful treatment of Mycobacterium ulcerans osteomyelitis with minor surgical debridement and prolonged rifampicin and ciprofloxacin therapy: a case report. J Med Case Rep 2:123

    Article  PubMed  PubMed Central  Google Scholar 

  289. Ji B, Chauffour A, Robert J, Lefrançois S, Jarlier V (2007) Orally administered combined regimens for treatment of Mycobacterium ulcerans infection in mice. Antimicrob Agents Chemother 51:3737–3739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  290. Marsollier L, Prévot G, Honoré N, Legras P, Manceau A-L, Payan C, Kouakou H, Carbonnelle B (2003) Susceptibility of Mycobacterium ulcerans to a combination of amikacin/rifampicin. Int J Antimicrob Agents 22:562–566

    Article  CAS  PubMed  Google Scholar 

  291. Nienhuis WA, Stienstra Y, Thompson WA, Awuah PC, Abass KM, Tuah W, Awua-Boateng NY, Ampadu EO, Siegmund V, Schouten JP (2010) Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial. Lancet 375:664–672

    Article  CAS  PubMed  Google Scholar 

  292. Klis S, Stienstra Y, Phillips RO, Abass KM, Tuah W, van der Werf TS (2014) Long term streptomycin toxicity in the treatment of Buruli ulcer: follow-up of participants in the BURULICO drug trial. PLoS Negl Trop Dis 8:e2739

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  293. Omansen TF, Porter JL, Johnson PD, van der Werf TS, Stienstra Y, Stinear TP (2015) In-vitro activity of avermectins against Mycobacterium ulcerans. PLoS Negl Trop Dis 9:e0003549

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  294. Meyers WM, Shelly WM, Connor DH (1974) Heat treatment of Mycobacterium ulcerans infections without surgical excision. Am J Trop Med Hyg 23:924–929

    Article  CAS  PubMed  Google Scholar 

  295. Junghanss T, Boock AU, Vogel M, Schuette D, Weinlaeder H, Pluschke G (2009) Phase change material for thermotherapy of Buruli ulcer: a prospective observational single centre proof-of-principle trial. PLoS Negl Trop Dis 3:e380

    Article  PubMed  PubMed Central  Google Scholar 

  296. Phillips R, Adjei O, Lucas S, Benjamin N, Wansbrough-Jones M (2004) Pilot randomized double-blind trial of treatment of Mycobacterium ulcerans disease (Buruli ulcer) with topical nitrogen oxides. Antimicrob Agents Chemother 48:2866–2870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  297. Phillips R, Kuijper S, Benjamin N, Wansbrough-Jones M, Wilks M, Kolk A (2004) In vitro killing of Mycobacterium ulcerans by acidified nitrite. Antimicrob Agents Chemother 48:3130–3132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  298. Adjei O, Evans M, Asiedu A (1998) Phenytoin in the treatment of Buruli ulcer. Trans R Soc Trop Med Hyg 92:108–109

    Article  CAS  PubMed  Google Scholar 

  299. Krieg R, Wolcott J, Confer A (1975) Treatment of Mycobacterium ulcerans infection by hyperbaric oxygenation. Aviat Space Environ Med 46:1241–1245

    CAS  PubMed  Google Scholar 

  300. Krieg R, Wolcott J, Meyers W (1979) Mycobacterium ulcerans infection: treatment with rifampin, hyperbaric oxygenation, and heat. Aviat Space Environ Med 50:888–892

    CAS  PubMed  Google Scholar 

  301. Portaels F, Aguiar J, Debacker M, Guedenon A, Steunou C, Zinsou C, Meyers W (2004) Mycobacterium bovis BCG vaccination as prophylaxis against Mycobacterium ulcerans osteomyelitis in Buruli ulcer disease. Infect Immun 72:62–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  302. Horwitz MA, Harth G, Dillon BJ, Masleša-Galić S (2005) Enhancing the protective efficacy of Mycobacterium bovis BCG vaccination against tuberculosis by boosting with the Mycobacterium tuberculosis major secretory protein. Infect Immun 73:4676–4683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  303. Magalhaes I, Sizemore DR, Ahmed RK, Mueller S, Wehlin L, Scanga C, Weichold F, Schirru G, Pau MG, Goudsmit J (2008) rBCG induces strong antigen-specific T cell responses in rhesus macaques in a prime-boost setting with an adenovirus 35 tuberculosis vaccine vector. PLoS One 3:e3790

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  304. Von Eschen K, Morrison R, Braun M, Ofori-Anyinam O, De Kock E, Pavithran P, Koutsoukos M, Moris P, Cain D, Dubois M-C (2009) The candidate tuberculosis vaccine Mtb72F/AS02A: tolerability and immunogenicity in humans. Hum Vaccin 5:475–482

    Article  Google Scholar 

  305. Skeiky YA, Dietrich J, Lasco TM, Stagliano K, Dheenadhayalan V, Goetz MA, Cantarero L, Basaraba RJ, Bang P, Kromann I (2010) Non-clinical efficacy and safety of HyVac4: IC31 vaccine administered in a BCG prime–boost regimen. Vaccine 28:1084–1093

    Article  CAS  PubMed  Google Scholar 

  306. Van Dissel JT, Soonawala D, Joosten SA, Prins C, Arend SM, Bang P, Tingskov PN, Lingnau K, Nouta J, Hoff ST (2011) Ag85B–ESAT-6 adjuvanted with IC31® promotes strong and long-lived Mycobacterium tuberculosis specific T cell responses in volunteers with previous BCG vaccination or tuberculosis infection. Vaccine 29:2100–2109

    Article  PubMed  CAS  Google Scholar 

  307. McShane H, Pathan AA, Sander CR, Keating SM, Gilbert SC, Huygen K, Fletcher HA, Hill AV (2004) Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat Med 10:1240–1244

    Article  CAS  PubMed  Google Scholar 

  308. Einarsdottir T, Huygen K (2011) Buruli ulcer. Hum Vaccin 7:1198–1203

    Article  CAS  PubMed  Google Scholar 

  309. Tanghe A, Van Vooren J-P, Portaels F, Huygen K (2001) Protective efficacy of a DNA vaccine encoding antigen 85A from Mycobacterium bovis BCG against Buruli ulcer. Infect Immun 69:5403–5411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  310. Tanghe A, Dangy J-P, Pluschke G, Huygen K (2008) Improved protective efficacy of a species-specific DNA vaccine encoding mycolyl-transferase Ag85A from Mycobacterium ulcerans by homologous protein boosting. PLoS Negl Trop Dis 2:e199

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  311. Coutanceau E, Legras P, Marsollier L, Reysset G, Cole ST, Demangel C (2006) Immunogenicity of Mycobacterium ulcerans Hsp65 and protective efficacy of a Mycobacterium leprae Hsp65-based DNA vaccine against Buruli ulcer. Microbes Infect 8:2075–2081

    Article  CAS  PubMed  Google Scholar 

  312. Nguyen TTH, Bezouska K, Vavrincova P, Sedlacek P, Hromadnikova I (2008) Humoral response against Mycobacterium bovis Hsp65 derived fragments in children and young people with various disorders. J Immunoass Immunochem 29:281–298

    Article  CAS  Google Scholar 

  313. Dawson CR, Schachter J (2013) Trachoma. Oxford University Press, Oxford

    Google Scholar 

  314. Bechtle M, Chen S, Efferth T (2010) Neglected diseases caused by bacterial infections. Curr Med Chem 17:42–60

    Article  CAS  PubMed  Google Scholar 

  315. Bryan CP (1930) The papyrus Ebers. Bles, London (translated from the German version)

    Google Scholar 

  316. WHO (2014) Visual impairment and blindness. Fact sheet N°282. World Health Organization, Geneva. http://www.who.int/mediacentre/factsheets/fs282/en/

  317. WHO (2013) Blinding trachoma fact sheet N°382. World Health Organization, Geneva. http://www.who.int/mediacentre/factsheets/fs382/en/

  318. Tabbara KF, Al-Omar OM (1997) Trachoma in Saudi Arabia. Ophthalmic Epidemiol 4:127–140

    Article  CAS  PubMed  Google Scholar 

  319. Khandekar R, Mohammed AJ (2007) The prevalence of trachomatous trichiasis in Oman (Oman eye study 2005). Ophthalmic Epidemiol 14:267–272

    Article  PubMed  Google Scholar 

  320. Taylor HR (2008) Trachoma: a blinding scourge from the Bronze Age to the twenty-first century. Centre for Eye Research Australia, East Melbourne

    Google Scholar 

  321. West S, Muñoz B, Lynch M, Kayongoya A, Chilangwa Z, Mmbaga B, Taylor HR (1995) Impact of face-washing on trachoma in Kongwa, Tanzania. Lancet 345:155–158

    Article  CAS  PubMed  Google Scholar 

  322. Emerson PM, Bailey RL, Mahdi OS, Walraven GE, Lindsay SW (2000) Transmission ecology of the fly Musca sorbens, a putative vector of trachoma. Trans R Soc Trop Med Hyg 94:28–32

    Article  CAS  PubMed  Google Scholar 

  323. Miller K, Pakpour N, Yi E, Melese M, Alemayehu W, Bird M, Schmidt G, Cevallos V, Olinger L, Chidambaram J (2004) Pesky trachoma suspect finally caught. Br J Ophthalmol 88:750–751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  324. Emerson PM, Lindsay SW, Alexander N, Bah M, Dibba S-M, Faal HB, Lowe K, McAdam KP, Ratcliffe AA, Walraven GE (2004) Role of flies and provision of latrines in trachoma control: cluster-randomised controlled trial. Lancet 363:1093–1098

    Article  PubMed  Google Scholar 

  325. Smith JL, Flueckiger RM, Hooper PJ, Polack S, Cromwell EA, Palmer SL, Emerson PM, Mabey DC, Solomon AW, Haddad D (2013) The geographical distribution and burden of trachoma in Africa. PLoS Negl Trop Dis 7:e2359

    Article  PubMed  PubMed Central  Google Scholar 

  326. Solomon AW, Pavluck AL, Courtright P, Aboe A, Adamu L, Alemayehu W, Alemu M, Alexander ND, Kello AB, Bero B (2015) The global trachoma mapping project: methodology of a 34-country population-based study. Ophthalmic Epidemiol 22:214–225

    Article  PubMed  PubMed Central  Google Scholar 

  327. Burton MJ, Mabey D (2009) The global burden of trachoma: a review. PLoS Negl Trop Dis 3:e460

    Article  PubMed  PubMed Central  Google Scholar 

  328. West SK, Munoz B, TURNER VM, Mmbaga B, TAYLOR HR (1991) The epidemiology of trachoma in central Tanzania. Int J Epidemiol 20:1088–1092

    Article  CAS  PubMed  Google Scholar 

  329. Ngondi J, Onsarigo A, Adamu L, Matende I, Baba S, Reacher M, Emerson P, Zingeser J (2005) The epidemiology of trachoma in Eastern Equatoria and Upper Nile States, Southern Sudan. Bull World Health Organ 83:904–912

    PubMed  Google Scholar 

  330. Ngondi J, Gebre T, Shargie EB, Adamu L, Ejigsemahu Y, Teferi T, Zerihun M, Ayele B, Cevallos V, King J (2009) Evaluation of three years of the SAFE strategy (surgery, antibiotics, facial cleanliness and environmental improvement) for trachoma control in five districts of Ethiopia hyperendemic for trachoma. Trans R Soc Trop Med Hyg 103:1001–1010

    Article  PubMed  Google Scholar 

  331. Courtright P, Sheppard J, Schachter J, Said M, Dawson C (1989) Trachoma and blindness in the Nile Delta: current patterns and projections for the future in the rural Egyptian population. Br J Ophthalmol 73:536–540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  332. Halberstaedter L, von Prowazek S (1907) Ueber Zelleinschlüsse parasitärer Natur beim trachom. Arb K GesundhAmte 26:44–47

    Google Scholar 

  333. Tang F, Chang H, Huang Y, Wang K (1957) Studies on the etiology of trachoma with special reference to isolation of the virus in chick embryo. Chin Med J (Engl) 75:429–447

    CAS  Google Scholar 

  334. Collier L, Duke-Elder S, Jones BR (1958) Experimental trachoma produced by cultured virus. Br J Ophthalmol 42:705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  335. Cho N-J, Potroz MG (2015) Natural products for the treatment of trachoma and Chlamydia trachomatis. Molecules 20:4180–4203

    Article  PubMed  CAS  Google Scholar 

  336. Byrne GI (2003) Chlamydia uncloaked. Proc Natl Acad Sci 100:8040–8042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  337. Burton MJ (2007) Trachoma: an overview. Br Med Bull 84:99–116

    Article  PubMed  Google Scholar 

  338. Andreasen AA, Burton MJ, Holland MJ, Polley S, Faal N, Mabey DC, Bailey RL (2008) Chlamydia trachomatis ompA variants in trachoma: what do they tell us? PLoS Negl Trop Dis 2:e306

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  339. Grayston JT, Wang S-P, Yeh L-J, Kuo C-C (1985) Importance of reinfection in the pathogenesis of trachoma. Rev Infect Dis 7:717–725

    Article  CAS  PubMed  Google Scholar 

  340. Ortiz L, Angevine M, Kim S-K, Watkins D, DeMars R (2000) T-cell epitopes in variable segments of Chlamydia trachomatis major outer membrane protein Elicit Serovar-specific immune responses in infected humans. Infect Immun 68:1719–1723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  341. Clarke IN (2011) Evolution of Chlamydia trachomatis. Ann N Y Acad Sci 1230:E11–E18

    Article  PubMed  Google Scholar 

  342. Matsumoto A (1988) Structural characteristics of chlamydial bodies. In: Barron AL (ed) Microbiology of Chlamydia. CRC, Boca Raton

    Google Scholar 

  343. Moulder JW (1991) Interaction of chlamydiae and host cells in vitro. Microbiol Rev 55:143

    CAS  PubMed  PubMed Central  Google Scholar 

  344. AbdelRahman YM, Belland RJ (2005) The chlamydial developmental cycle. FEMS Microbiol Rev 29:949–959

    Article  CAS  PubMed  Google Scholar 

  345. Brunham RC, Rey-Ladino J (2005) Immunology of Chlamydia infection: implications for a Chlamydia trachomatis vaccine. Nat Rev Immunol 5:149–161

    Article  CAS  PubMed  Google Scholar 

  346. Chen JC-R, Stephens RS (1997) Chlamydia trachomatis glycosaminoglycan-dependent and independent attachment to eukaryotic cells. Microb Pathog 22:23–30

    Article  CAS  PubMed  Google Scholar 

  347. Hackstadt T, Todd W, Caldwell H (1985) Disulfide-mediated interactions of the chlamydial major outer membrane protein: role in the differentiation of chlamydiae? J Bacteriol 161:25–31

    CAS  PubMed  PubMed Central  Google Scholar 

  348. Beatty WL, Morrison RP, Byrne GI (1994) Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis. Microbiol Rev 58:686–699

    CAS  PubMed  PubMed Central  Google Scholar 

  349. Kalayoglu MV (2002) Ocular chlamydial infections: pathogenesis and emerging treatment strategies. Curr Drug Targets Infect Disord 2:85–91

    Article  CAS  PubMed  Google Scholar 

  350. Hatch T, Al-Hossainy E, Silverman J (1982) Adenine nucleotide and lysine transport in Chlamydia psittaci. J Bacteriol 150:662–670

    CAS  PubMed  PubMed Central  Google Scholar 

  351. Iliffe‐Lee ER, McClarty G (1999) Glucose metabolism in Chlamydia trachomatis: the ‘energy parasite’ hypothesis revisited. Mol Microbiol 33:177–187

    Article  PubMed  Google Scholar 

  352. McClarty G (1999) Chlamydial metabolism as inferred from the complete genome sequence. In: Chlamydia: intracellular biology, pathogenesis, and immunity. American Society for Microbiology, Washington, pp 69–100

    Chapter  Google Scholar 

  353. Stephens RS, Kalman S, Lammel C, Fan J, Marathe R, Aravind L, Mitchell W, Olinger L, Tatusov RL, Zhao Q (1998) Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282:754–759

    Article  CAS  PubMed  Google Scholar 

  354. Kalman S, Mitchell W, Marathe R, Lammel C, Fan J, Hyman RW, Olinger L, Grimwood J, Davis RW, Stephens R (1999) Comparative genomes of Chlamydia pneumoniae and C. trachomatis. Nat Genet 21:385–389

    Article  CAS  PubMed  Google Scholar 

  355. Carlson JH, Porcella SF, McClarty G, Caldwell HD (2005) Comparative genomic analysis of Chlamydia trachomatis oculotropic and genitotropic strains. Infect Immun 73:6407–6418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  356. Thomson NR, Holden MT, Carder C, Lennard N, Lockey SJ, Marsh P, Skipp P, O’Connor CD, Goodhead I, Norbertzcak H (2008) Chlamydia trachomatis: genome sequence analysis of lymphogranuloma venereum isolates. Genome Res 18:161–171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  357. Weiss E, Neptune E, Gaugler R (1968) Influence of gas environment on catabolic activities and on reoxidation of reduced nicotinamide adenine dinucleotide phosphate in Chlamydia. J Bacteriol 96:1567–1573

    CAS  PubMed  PubMed Central  Google Scholar 

  358. Weiss E (1967) Transaminase activity and other enzymatic reactions involving pyruvate and glutamate in Chlamydia (psittacosis-trachoma group). J Bacteriol 93:177–184

    CAS  PubMed  PubMed Central  Google Scholar 

  359. Cecchini G (2003) Function and structure of complex II of the respiratory chain. Annu Rev Biochem 72:77–109

    Article  CAS  PubMed  Google Scholar 

  360. Lancaster CRD (2013) The di-heme family of respiratory complex II enzymes. Biochim Biophys Acta Bioenerg 1827:679–687

    Article  CAS  Google Scholar 

  361. Yao J, Abdelrahman YM, Robertson RM, Cox JV, Belland RJ, White SW, Rock CO (2014) Type II fatty acid synthesis is essential for the replication of Chlamydia trachomatis. J Biol Chem 289:22365–22376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  362. Saka HA, Valdivia RH (2010) Acquisition of nutrients by Chlamydiae: unique challenges of living in an intracellular compartment. Curr Opin Microbiol 13:4–10

    Article  CAS  PubMed  Google Scholar 

  363. Sixt BS, Siegl A, Müller C, Watzka M, Wultsch A, Tziotis D, Montanaro J, Richter A, Schmitt-Kopplin P, Horn M (2013) Metabolic features of Protochlamydia amoebophila elementary bodies—a link between activity and infectivity in Chlamydiae. PLoS Pathog 9:e1003553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  364. Haider S, Wagner M, Schmid MC, Sixt BS, Christian JG, Häcker G, Pichler P, Mechtler K, Müller A, Baranyi C (2010) Raman microspectroscopy reveals long‐term extracellular activity of chlamydiae. Mol Microbiol 77:687–700

    Article  CAS  PubMed  Google Scholar 

  365. Collingro A, Tischler P, Weinmaier T, Penz T, Heinz E, Brunham RC, Read TD, Bavoil PM, Sachse K, Kahane S (2011) Unity in variety—the pan-genome of the Chlamydiae. Mol Biol Evol 28:3253–3270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  366. Thomas N, Lusher M, Storey C, Clarke I (1997) Plasmid diversity in Chlamydia. Microbiology 143:1847–1854

    Article  CAS  PubMed  Google Scholar 

  367. Pickett MA, Everson JS, Pead PJ, Clarke IN (2005) The plasmids of Chlamydia trachomatis and Chlamydophila pneumoniae (N16): accurate determination of copy number and the paradoxical effect of plasmid-curing agents. Microbiology 151:893–903

    Article  CAS  PubMed  Google Scholar 

  368. Rockey DD (2011) Unraveling the basic biology and clinical significance of the chlamydial plasmid. J Exp Med 208:2159–2162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  369. Seth-Smith HM, Harris SR, Persson K, Marsh P, Barron A, Bignell A, Bjartling C, Clark L, Cutcliffe LT, Lambden PR (2009) Co-evolution of genomes and plasmids within Chlamydia trachomatis and the emergence in Sweden of a new variant strain. BMC Genomics 10:239

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  370. Fredlund H, Falk L, Jurstrand M, Unemo M (2004) Molecular genetic methods for diagnosis and characterisation of Chlamydia trachomatis and Neisseria gonorrhoeae: impact on epidemiological surveillance and interventions. APMIS 112:771–784

    Article  CAS  PubMed  Google Scholar 

  371. Gaynor B, Chidambaram J, Cevallos V, Miao Y, Miller K, Jha H, Bhatta R, Chaudhary J, Holm SO, Whitcher J (2005) Topical ocular antibiotics induce bacterial resistance at extraocular sites. Br J Ophthalmol 89:1097–1099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  372. Rasmussen SJ, Eckmann L, Quayle AJ, Shen L, Zhang Y-X, Anderson DJ, Fierer J, Stephens RS, Kagnoff MF (1997) Secretion of proinflammatory cytokines by epithelial cells in response to Chlamydia infection suggests a central role for epithelial cells in chlamydial pathogenesis. J Clin Investig 99:77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  373. El-Asrar AMA, Tabbara KF, Al-Kharashi SA, Geboes K, Missotten L, Desmet V (1998) Immunopathogenesis of conjunctival scarring in trachoma. Eye 12:453–460

    Article  Google Scholar 

  374. Ingalls RR, Rice PA, Qureshi N, Takayama K, Lin JS, Golenbock DT (1995) The inflammatory cytokine response to Chlamydia trachomatis infection is endotoxin mediated. Infect Immun 63:3125–3130

    CAS  PubMed  PubMed Central  Google Scholar 

  375. Prebeck S, Kirschning C, Dürr S, da Costa C, Donath B, Brand K, Redecke V, Wagner H, Miethke T (2001) Predominant role of toll-like receptor 2 versus 4 in Chlamydia pneumoniae-induced activation of dendritic cells. J Immunol 167:3316–3323

    Article  CAS  PubMed  Google Scholar 

  376. Prebeck S, Brade H, Kirschning CJ, da Costa CP, Dürr S, Wagner H, Miethke T (2003) The gram-negative bacterium Chlamydia trachomatis L 2 stimulates tumor necrosis factor secretion by innate immune cells independently of its endotoxin. Microbes Infect 5:463–470

    Article  CAS  PubMed  Google Scholar 

  377. Heine H, Müller‐Loennies S, Brade L, Lindner B, Brade H (2003) Endotoxic activity and chemical structure of lipopolysaccharides from Chlamydia trachomatis serotypes E and L2 and Chlamydophila psittaci 6BC. Eur J Biochem 270:440–450

    Article  CAS  PubMed  Google Scholar 

  378. Kol A, Bourcier T, Lichtman AH, Libby P (1999) Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. J Clin Investig 103:571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  379. Kol A, Lichtman AH, Finberg RW, Libby P, Kurt-Jones EA (2000) Cutting edge: heat shock protein (HSP) 60 activates the innate immune response: CD14 is an essential receptor for HSP60 activation of mononuclear cells. J Immunol 164:13–17

    Article  CAS  PubMed  Google Scholar 

  380. Vabulas RM, Ahmad-Nejad P, da Costa C, Miethke T, Kirschning CJ, Häcker H, Wagner H (2001) Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem 276:31332–31339

    Article  CAS  PubMed  Google Scholar 

  381. Bulut Y, Faure E, Thomas L, Karahashi H, Michelsen KS, Equils O, Morrison SG, Morrison RP, Arditi M (2002) Chlamydial heat shock protein 60 activates macrophages and endothelial cells through toll-like receptor 4 and MD2 in a MyD88-dependent pathway. J Immunol 168:1435–1440

    Article  CAS  PubMed  Google Scholar 

  382. Costa CPD, Kirschning CJ, Busch D, Dürr S, Jennen L, Heinzmann U, Prebeck S, Wagner H, Miethke T (2002) Role of chlamydial heat shock protein 60 in the stimulation of innate immune cells by Chlamydia pneumoniae. Eur J Immunol 32:2460–2470

    Article  PubMed  Google Scholar 

  383. Bulut Y, Shimada K, Wong MH, Chen S, Gray P, Alsabeh R, Doherty TM, Crother TR, Arditi M (2009) Chlamydial heat shock protein 60 induces acute pulmonary inflammation in mice via the toll-like receptor 4-and MyD88-dependent pathway. Infect Immun 77:2683–2690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  384. Abdul-Sater AA, Koo E, Häcker G, Ojcius DM (2009) Inflammasome-dependent caspase-1 activation in cervical epithelial cells stimulates growth of the intracellular pathogen Chlamydia trachomatis. J Biol Chem 284:26789–26796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  385. Boncompain G, Schneider B, Delevoye C, Kellermann O, Dautry-Varsat A, Subtil A (2010) Production of reactive oxygen species is turned on and rapidly shut down in epithelial cells infected with Chlamydia trachomatis. Infect Immun 78:80–87

    Article  CAS  PubMed  Google Scholar 

  386. D'Autréaux B, Toledano MB (2007) ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8:813–824

    Article  PubMed  CAS  Google Scholar 

  387. Rank RG, Bowlin AK, Kelly KA (2000) Characterization of lymphocyte response in the female genital tract during ascending Chlamydial genital infection in the guinea pig model. Infect Immun 68:5293–5298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  388. Rank RG, Whittimore J, Bowlin AK, Dessus‐Babus S, Wyrick PB (2008) Chlamydiae and polymorphonuclear leukocytes: unlikely allies in the spread of chlamydial infection. FEMS Immunol Med Microbiol 54:104–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  389. Rank RG, Lacy HM, Goodwin A, Sikes J, Whittimore J, Wyrick PB, Nagarajan UM (2010) Host chemokine and cytokine response in the endocervix within the first developmental cycle of Chlamydia muridarum. Infect Immun 78:536–544

    Article  CAS  PubMed  Google Scholar 

  390. Tseng C-TK, Rank RG (1998) Role of NK cells in early host response to chlamydial genital infection. Infect Immun 66:5867–5875

    CAS  PubMed  PubMed Central  Google Scholar 

  391. Mabey DC, Solomon AW, Foster A (2003) Trachoma. Lancet 362:223–229

    Article  PubMed  Google Scholar 

  392. Fan T, Lu H, Hu H, Shi L, McClarty GA, Nance DM, Greenberg AH, Zhong G (1998) Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation. J Exp Med 187:487–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  393. Jendro MC, Fingerle F, Deutsch T, Liese A, Köhler L, Kuipers JG, Raum E, Martin M, Zeidler H (2004) Chlamydia trachomatis-infected macrophages induce apoptosis of activated T cells by secretion of tumor necrosis factor-α in vitro. Med Microbiol Immunol 193:45–52

    Article  CAS  PubMed  Google Scholar 

  394. Zhong G, Liu L, Fan T, Fan P, Ji H (2000) Degradation of transcription factor Rfx5 during the inhibition of both constitutive and interferon γ–inducible major histocompatibility complex class I expression in chlamydia-infected cells. J Exp Med 191:1525–1534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  395. WHO (2015) Trachoma grading card (side 1). World Health Organization, Geneva. http://www.who.int/blindness/publications/trachoma_english.jpg?ua=1. Accessed December 2015

  396. WHO (2015) Trachoma grading card (side 2). World Health Organization, Geneva. http://www.who.int/blindness/publications/trachoma_english1.jpg?ua=1. Accessed December 2015

  397. Reacher MH, Muñoz B, Alghassany A, Daar AS, Elbualy M, Taylor HR (1992) A controlled trial of surgery for trachomatous trichiasis of the upper lid. Arch Ophthalmol 110:667–674

    Article  CAS  PubMed  Google Scholar 

  398. WHO (2006) Blinding trachoma: progress towards global elimination by 2020. World Health Organization, Geneva. http://www.who.int/mediacentre/news/notes/2006/np09/en/.Accessed December 2015

  399. Rajak SN, Collin JRO, Burton MJ (2012) Trachomatous trichiasis and its management in endemic countries. Surv Ophthalmol 57:105–135

    Article  PubMed  Google Scholar 

  400. Burton M, Bowman R, Faal H, Aryee E, Ikumapayi U, Alexander N, Adegbola R, West S, Mabey D, Foster A (2005) Long term outcome of trichiasis surgery in the Gambia. Br J Ophthalmol 89:575–579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  401. WHO (1998) Global elimination of blinding trachoma: 51st World Health Assembly: Resolution 51.11.1998. World Health Organization, Geneva

    Google Scholar 

  402. Prüss A, Mariotti SP (2000) Preventing trachoma through environmental sanitation: a review of the evidence base. Bull World Health Organ 78:267–273

    Google Scholar 

  403. Emerson PM, Lindsay SW, Walraven GE, Faal H, Bøgh C, Lowe K, Bailey RL (1999) Effect of fly control on trachoma and diarrhoea. Lancet 353:1401–1403

    Article  CAS  PubMed  Google Scholar 

  404. Thylefors B (1985) Development of trachoma control programs and the involvement of national resources. Rev Infect Dis 7:774–776

    Article  CAS  PubMed  Google Scholar 

  405. Schachter J (1983) Rifampin in chlamydial infections. Rev Infect Dis 5:S562–S564

    Article  PubMed  Google Scholar 

  406. Darougar S, Jones B, Viswalingam N, Poirier R, Allami J, Houshmand A, Farahmandian M, Gibson J (1980) Family-based suppressive intermittent therapy of hyperendemic trachoma with topical oxytetracycline or oral doxycycline. Br J Ophthalmol 64:291–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  407. Hoshiwara I, Ostler HB, Hanna L, Cignetti F, Coleman VR, Jawetz E (1973) Doxycycline treatment of chronic trachoma. JAMA 224:220–223

    Article  CAS  PubMed  Google Scholar 

  408. Tabbara KF, Summanen P, Taylor PB, Burd EM, Al Omar O (1988) Minocycline effects in patients with active trachoma. Int Ophthalmol 12:59–63

    Article  CAS  PubMed  Google Scholar 

  409. Tabbara KF (2001) Blinding trachoma: the forgotten problem. Br J Ophthalmol 85:1397–1399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  410. Bailey R, Arullendran P, Mabey D, Whittle H (1993) Randomised controlled trial of single-dose azithromycin in treatment of trachoma. Lancet 342:453–456

    Article  CAS  PubMed  Google Scholar 

  411. Cochereau I, Goldschmidt P, Goepogui A, Afghani T, Delval L, Pouliquen P, Bourcier T, Robert P-Y (2007) Efficacy and safety of short duration azithromycin eye drops versus azithromycin single oral dose for the treatment of trachoma in children: a randomised, controlled, double-masked clinical trial. Br J Ophthalmol 91:667–672

    Article  PubMed  Google Scholar 

  412. Dawson C, Schachter J, Sallam S, Sheta A, Rubinstein R, Washton H (1997) A comparison of oral azithromycin with topical oxytetracycline/polymyxin for the treatment of trachoma in children. Clin Infect Dis 24:363–368

    Article  CAS  PubMed  Google Scholar 

  413. Nelson ML (2002) The chemistry and biology of the tetracyclines. Annu Rep Med Chem 37:105–114

    CAS  Google Scholar 

  414. Genilloud O, Vicente F (2013) Tetracycline antibiotics and novel analogs. Springer, Berlin

    Google Scholar 

  415. Chopra I, Hawkey P, Hinton M (1992) Tetracyclines, molecular and clinical aspects. J Antimicrob Chemother 29:245–277

    Article  CAS  PubMed  Google Scholar 

  416. Nikaido H, Thanassi D (1993) Penetration of lipophilic agents with multiple protonation sites into bacterial cells: tetracyclines and fluoroquinolones as examples. Antimicrob Agents Chemother 37:1393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  417. Schnappinger D, Hillen W (1996) Tetracyclines: antibiotic action, uptake, and resistance mechanisms. Arch Microbiol 165:359–369

    Article  CAS  PubMed  Google Scholar 

  418. Goldman RA, Hasan T, Hall CC, Strycharz WA, Cooperman BS (1983) Photoincorporation of tetracycline into Escherichia coli ribosomes. Identification of the major proteins photolabeled by native tetracycline and tetracycline photoproducts and implications for the inhibitory action of tetracycline on protein synthesis. Biochemistry 22:359–368

    Article  CAS  PubMed  Google Scholar 

  419. Zakeri B, Wright GD (2008) Chemical biology of tetracycline antibiotics. Biochem Cell Biol 86:124–136

    Article  CAS  PubMed  Google Scholar 

  420. Chiu LM, Amsden GW (2002) Current trachoma treatment methodologies. Drugs 62:2573–2579

    Article  CAS  PubMed  Google Scholar 

  421. Baltussen RM, Sylla M, Frick KD, Mariotti SP (2005) Cost-effectiveness of trachoma control in seven world regions. Ophthalmic Epidemiol 12:91–101

    Article  PubMed  Google Scholar 

  422. Hoepelman I, Schneider M (1995) Azithromycin: the first of the tissue-selective azalides. Int J Antimicrob Agents 5:145–167

    Article  CAS  PubMed  Google Scholar 

  423. Greenwood D (2008) Antimicrobial drugs: chronicle of a twentieth century medical triumph. Oxford University Press, New York

    Google Scholar 

  424. Hirsch R, Deng H, Laohachai M (2012) Azithromycin in periodontal treatment: more than an antibiotic. J Periodontal Res 47:137–148

    Article  CAS  PubMed  Google Scholar 

  425. Mao JC, Robishaw EE (1972) Erythromycin, a peptidyltransferase effector. Biochemistry 11:4864–4872

    Article  CAS  PubMed  Google Scholar 

  426. Gaynor M, Mankin AS (2003) Macrolide antibiotics: binding site, mechanism of action, resistance. Curr Top Med Chem 3:949–960

    Article  CAS  PubMed  Google Scholar 

  427. Garza-Ramos G, Xiong L, Zhong P, Mankin A (2001) Binding site of macrolide antibiotics on the ribosome: new resistance mutation identifies a specific interaction of ketolides with rRNA. J Bacteriol 183:6898–6907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  428. Sugie M, Asakura E, Zhao YL, Torita S, Nadai M, Baba K, Kitaichi K, Takagi K, Takagi K, Hasegawa T (2004) Possible involvement of the drug transporters P glycoprotein and multidrug resistance-associated protein Mrp2 in disposition of azithromycin. Antimicrob Agents Chemother 48:809–814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  429. Ballow CH, Amsden GW, Highet VS, Forrest A (1998) Pharmacokinetics of oral azithromycin in serum, urine, polymorphonuclear leucocytes and inflammatory vs non-inflammatory skin blisters in healthy volunteers. Clin Drug Investig 15:159–167

    Article  CAS  PubMed  Google Scholar 

  430. Amacher D, Schomaker S, Retsema J (1991) Comparison of the effects of the new azalide antibiotic, azithromycin, and erythromycin estolate on rat liver cytochrome P-450. Antimicrob Agents Chemother 35:1186–1190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  431. Drugs.com (2015) Azithromycin side effects. http://www.drugs.com/sfx/azithromycin-side-effects.html. Accessed December 2015

  432. Dawson CR, Daghfous T, Hoshiwara I, Ramdhane K, Kamoun M, Yoneda C, Schachter J (1982) Trachoma therapy with topical tetracycline and oral erythromycin: a comparative trial. Bull World Health Organ 60:347

    CAS  PubMed  PubMed Central  Google Scholar 

  433. Suchland R, Sandoz K, Jeffrey B, Stamm W, Rockey D (2009) Horizontal transfer of tetracycline resistance among Chlamydia spp. in vitro. Antimicrob Agents Chemother 53:4604–4611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  434. West SK, Moncada J, Munoz B, Mkocha H, Storey P, Hardick J, Gaydos CA, Quinn TC, Schachter J (2014) Is there evidence for resistance of ocular Chlamydia trachomatis to azithromycin after mass treatment for trachoma control? J Infect Dis 210:65–71

    Article  CAS  PubMed  Google Scholar 

  435. Leach AJ, Shelby-James TM, Mayo M, Gratten M, Laming AC, Currie BJ, Mathews JD (1997) A prospective study of the impact of community-based azithromycin treatment of trachoma on carriage and resistance of Streptococcus pneumoniae. Clin Infect Dis 24:356–362

    Article  CAS  PubMed  Google Scholar 

  436. Keenan JD, Sahlu I, McGee L, Cevallos V, Vidal JE, Chochua S, Hawkins P, Gebre T, Tadesse Z, Emerson PM et al (2015) Nasopharyngeal pneumococcal serotypes before and after mass azithromycin distributions for trachoma. J Pediatr Infect Dis Soc. doi:10.1093/jpids/piu1143

    Article  Google Scholar 

  437. Kuper H, Solomon AW, Buchan J, Zondervan M, Foster A, Mabey D (2003) A critical review of the SAFE strategy for the prevention of blinding trachoma. Lancet Infect Dis 3:372–381

    Article  PubMed  Google Scholar 

  438. Beagley KW, Timms P (2000) Chlamydia trachomatis infection: incidence, health costs and prospects for vaccine development. J Reprod Immunol 48:47–68

    Article  CAS  PubMed  Google Scholar 

  439. Kim S-K, DeMars R (2001) Epitope clusters in the major outer membrane protein of Chlamydia trachomatis. Curr Opin Immunol 13:429–436

    Article  CAS  PubMed  Google Scholar 

  440. Stephens RS, Wagar EA, Schoolnik G (1988) High-resolution mapping of serovar-specific and common antigenic determinants of the major outer membrane protein of Chlamydia trachomatis. J Exp Med 167:817–831

    Article  CAS  PubMed  Google Scholar 

  441. Baehr W, Zhang Y-X, Joseph T, Su H, Nano FE, Everett K, Caldwell HD (1988) Mapping antigenic domains expressed by Chlamydia trachomatis major outer membrane protein genes. Proc Natl Acad Sci 85:4000–4004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  442. Campos M, Pal S, O'Brien TP, Taylor HR, Prendergast RA, Whittum-Hudson JA (1995) A chlamydial major outer membrane protein extract as a trachoma vaccine candidate. Investig Ophthalmol Vis Sci 36:1477

    CAS  Google Scholar 

  443. Taylor HR, Whittum-Hudson J, Schachter J, Caldwell H, Prendergast R (1988) Oral immunization with chlamydial major outer membrane protein (MOMP). Investig Ophthalmol Vis Sci 29:1847–1853

    CAS  Google Scholar 

  444. Zhang D-J, Yang X, Berry J, Shen C, McClarty G, Brunham RC (1997) DNA vaccination with the major outer-membrane protein gene induces acquired immunity to Chlamydia trachomatis (mouse pneumonitis) infection. J Infect Dis 176:1035–1040

    Article  CAS  PubMed  Google Scholar 

  445. Kari L, Whitmire WM, Crane DD, Reveneau N, Carlson JH, Goheen MM, Peterson EM, Pal S, Luis M, Caldwell HD (2009) Chlamydia trachomatis native major outer membrane protein induces partial protection in nonhuman primates: implication for a trachoma transmission-blocking vaccine. J Immunol 182:8063–8070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  446. Swanson KA, Crane DD, Caldwell HD (2007) Chlamydia trachomatis species-specific induction of ezrin tyrosine phosphorylation functions in pathogen entry. Infect Immun 75:5669–5677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  447. Wehrl W, Brinkmann V, Jungblut PR, Meyer TF, Szczepek AJ (2004) From the inside out–processing of the Chlamydial autotransporter PmpD and its role in bacterial adhesion and activation of human host cells. Mol Microbiol 51:319–334

    Article  CAS  PubMed  Google Scholar 

  448. Crane DD, Carlson JH, Fischer ER, Bavoil P, Hsia R-C, Tan C, Kuo C-C, Caldwell HD (2006) Chlamydia trachomatis polymorphic membrane protein D is a species-common pan-neutralizing antigen. Proc Natl Acad Sci USA 103:1894–1899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  449. Liu MA, Wahren B, Hedestam GBK (2006) DNA vaccines: recent developments and future possibilities. Hum Gene Ther 17:1051–1061

    Article  CAS  PubMed  Google Scholar 

  450. Zhang D, Yang X, Shen C, Brunham R (1999) Characterization of immune responses following intramuscular DNA immunization with the MOMP gene of Chlamydia trachomatis mouse pneumonitis strain. Immunology 96:314–321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  451. Penttilä T, Vuola JM, Puurula V, Anttila M, Sarvas M, Rautonen N, Mäkelä PH, Puolakkainen M (2000) Immunity to Chlamydia pneumoniae induced by vaccination with DNA vectors expressing a cytoplasmic protein (Hsp60) or outer membrane proteins (MOMP and Omp2). Vaccine 19:1256–1265

    Article  PubMed  Google Scholar 

  452. Ramshaw IA, Ramsay AJ (2000) The prime-boost strategy: exciting prospects for improved vaccination. Immunol Today 21:163–165

    Article  CAS  PubMed  Google Scholar 

  453. Hajek R, Butch A (2000) Dendritic cell biology and the application of dendritic cells to immunotherapy of multiple myeloma. Med Oncol 17:2–15

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow, 226031, India

    Anil Kumar Saxena

  2. “Hygeia” Centre of Excellence in Pharmaceutical Sciences (CEPS), GGS Indraprastha University, Sec. 16-C, Dwarka, New Delhi, 110078, India

    Chandra Sourabh Azad

Authors
  1. Anil Kumar Saxena
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chandra Sourabh Azad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anil Kumar Saxena .

Editor information

Editors and Affiliations

  1. Division of Medicinal & Process Chemistry, Central Drug Research Institute, Lucknow, Uttar Pradesh, India

    Anil Kumar Saxena

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Saxena, A.K., Azad, C.S. (2016). Neglected Tropical Bacterial Diseases. In: Saxena, A. (eds) Communicable Diseases of the Developing World. Topics in Medicinal Chemistry, vol 29. Springer, Cham. https://doi.org/10.1007/7355_2016_5

Download citation

Publish with us

Policies and ethics

Search

Navigation