The resumption of consumption - A review on tuberculosis

Rodrigo G. Ducati, Antonio Ruffino-Netto, Luiz Augusto Basso, Diógenes Santiago Santos

Research output: Contribution to journalReview article

124 Citations (Scopus)

Abstract

Among all infectious diseases that afflict humans, tuberculosis (TB) remains the deadliest. At present, epidemiologists estimate that one-third of the world population is infected with tubercle bacilli, which is responsible for 8 to 10 million new cases of TB and 3 million deaths annually throughout the world. Approximately 95% of new cases and 98% of deaths occur in developing nations, generally due to the few resources available to ensure proper treatment and where human immunodeficiency virus (HIV) infections are common. In 1882, Dr Robert Koch identified an acidfast bacterium, Mycobacterium tuberculosis, as the causative agent of TB. Thirty-nine years later, BCG vaccine was introduced for human use, and became the most widely used prophylactic strategy to fight TB in the world. The discovery of the properties of first-line antimycobacterial drugs in the past century yielded effective chemotherapies, which considerably decreased TB mortality rates worldwide. The later introduction of some additional drugs to the arsenal used to treat TB seemed to provide an adequate number of effective antimicrobial agents. The modern, standard short-course therapy for TB recommended by the World Health Organization is based on a four-drug regimen that must be strictly followed to prevent drug resistance acquisition, and relies on direct observation of patient compliance to ensure effective treatment. Mycobacteria show a high degree of intrinsic resistance to most antibiotics and chemotherapeutic agents due to the low permeability of its cell wall. Nevertheless, the cell wall barrier alone cannot produce significant levels of drug resistance. M. tuberculosis mutants resistant to any single drug are naturally present in any large bacterial population, irrespective of exposure to drugs. The frequency of mutants resistant to rifampicin and isoniazid, the two principal antimycobacterial drugs currently in use, is relatively high and, therefore, the large extra-cellular population of actively metabolizing and rapidly growing tubercle bacilli in cavitary lesions will contain organisms which are resistant to a single drug. Consequently, monotherapy or improperly administered two-drug therapies will select for drug-resistant mutants that may lead to drug resistance in the entire bacterial population. Thereby, despite the availability of effective chemotherapy and the moderately protective vaccine, new anti-TB agents are urgently needed to decrease the global incidence of TB. The resumption of TB, mainly caused by the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains and HIV epidemics, led to an increased need to understand the molecular mechanisms of drug action and drug resistance, which should provide significant insight into the development of newer compounds. The latter should be effective to combat both drugsusceptible and MDR/XDR-TB.

Original languageEnglish (US)
Pages (from-to)697-714
Number of pages18
JournalMemorias do Instituto Oswaldo Cruz
Volume101
Issue number7
StatePublished - 2006
Externally publishedYes

Fingerprint

Tuberculosis
Pharmaceutical Preparations
Drug Resistance
Mycobacterium tuberculosis
Drug Therapy
Cell Wall
Bacillus
Population
Chemotherapy
Bacilli
HIV
Viruses
BCG Vaccine
Multidrug-Resistant Tuberculosis
Isoniazid
Virus Diseases
Cells
Rifampin
Mycobacterium
Patient Compliance

Keywords

  • Chemotherapy
  • Drug action
  • Epidemiology
  • Mechanism of resistance
  • Mycobacterium tuberculosis
  • Vaccine

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology
  • Immunology
  • Microbiology (medical)
  • Clinical Biochemistry

Cite this

Ducati, R. G., Ruffino-Netto, A., Basso, L. A., & Santos, D. S. (2006). The resumption of consumption - A review on tuberculosis. Memorias do Instituto Oswaldo Cruz, 101(7), 697-714.

The resumption of consumption - A review on tuberculosis. / Ducati, Rodrigo G.; Ruffino-Netto, Antonio; Basso, Luiz Augusto; Santos, Diógenes Santiago.

In: Memorias do Instituto Oswaldo Cruz, Vol. 101, No. 7, 2006, p. 697-714.

Research output: Contribution to journalReview article

Ducati, RG, Ruffino-Netto, A, Basso, LA & Santos, DS 2006, 'The resumption of consumption - A review on tuberculosis', Memorias do Instituto Oswaldo Cruz, vol. 101, no. 7, pp. 697-714.
Ducati RG, Ruffino-Netto A, Basso LA, Santos DS. The resumption of consumption - A review on tuberculosis. Memorias do Instituto Oswaldo Cruz. 2006;101(7):697-714.
Ducati, Rodrigo G. ; Ruffino-Netto, Antonio ; Basso, Luiz Augusto ; Santos, Diógenes Santiago. / The resumption of consumption - A review on tuberculosis. In: Memorias do Instituto Oswaldo Cruz. 2006 ; Vol. 101, No. 7. pp. 697-714.
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