Tropical dermatology: bacterial tropical diseases / Tropical dermatology: bacterial tropical diseases

Bacterial infections are common in tropical parts of the world and can include those species also seen regularly in temperate climates. Many tropical bacterial infections, however, are rarely diagnosed in temperate parts of the world and include bartonellosis, tropical ulcer, tropical pyomyositis, granuloma inguinale, lymphogranuloma venereum, yaws, pinta, melioidosis, and glanders. Some tropical bacterial diseases, eg, plague and anthrax, are associated with high mortality rates and are of potential use in bioterrorism. Some tropical bacterial diseases are closely associated with specific activities such as hunting (ie, tularemia) or eating raw seafood (Vibrio vulnificus infection). The bacterial diseases having the most severe medical impact in the tropics are those caused by members of the Mycobacterium genus. Millions of persons throughout the world suffer from tuberculosis and leprosy; Buruli ulcers are common causes of morbidity in many tropical countries. Because of the increasing frequency of travel to tropical parts of the world for tourism and work as well as the increasing number of immigrants and adoptees from these areas, it is imperative that physicians practicing in temperate climates be able to recognize the signs and symptoms of tropical bacterial diseases, carry out the proper diagnostic tests, and initiate appropriate therapy and prevention. LEARNING OBJECTIVE: At the completion of this learning activity, participants should be familiar with the clinical presentations, epidemiologies, diagnoses, therapies, and preventions of bacterial tropical diseases...

Macrophage NRAMP1 and its role in resistance to microbial infections.

The identification and characterization of genetic factors influencing natural susceptibility to infectious diseases in humans and in model organisms, such as the laboratory mouse, can provide new insight into the basic mechanisms of host defense against infections. In the mouse, resistance or susceptibility to infection with intracellular pathogens such as Salmonella, Mycobacterium and Leishmnania is controlled by the Natural resistance associated macrophage protein (Nramp1) gene on chromosome 1, which influences the rate of intracellular replication of these parasites in macrophages. Nramp1 codes for an integral membrane protein, which is expressed exclusively in macrophage/monocytes and polymorphonuclear leukocytes. The protein is localized to the endosomal/lysosomal compartment of the macrophage and is rapidly recruited to the membrane of the particle-containing phagosome upon phagocytosis. Nramp defines a novel family of functionally related membrane proteins including Nramp2, which was recently shown to be the major transferrin-independent uptake system of the intestine in mammals. This observation supports the hypothesis that the phagocyte-specific Nramp1 protein may regulate the intraphagosomal replication of antigenically unrelated bacteria by controlling divalent cation concentrations at that site. Recent genetic studies have found that allelic variants at the human NRAMP1 locus are associated with susceptibility to leprosy (Mycobacterium leprae) and tuberculosis (Mycobacterium tuberculosis) and possibly with the onset of rheumatoid arthritis.

Quinolones in intracellular infections.

Intracellular parasites are those which spend most of their lives within host cells. The fluoroquinolones demonstrate favourable intracellular pharmacokinetics for the treatment of intracellular infections; these agents diffuse and accumulate in the phagocytes, mainly in the cytosol, and do not associate with cellular organelles. The fluoroquinolones are generally active against Salmonella spp. in vitro, and have been used successfully in the treatment of typhoid fever, Salmonella bacteraemia in patients with AIDS, and chronic enteric carriage. Fluoroquinolone monotherapy has also been found satisfactory in the treatment of tularaemia and Mediterranean spotted fever. Quinolones, alone or in combination with other agents, have also shown promise in animal models of legionellosis and in limited clinical studies. Quinolones, particularly ciprofloxacin and ofloxacin, have notable antimycobacterial activity. Both agents have been used in combination with other antimycobacterial drugs in the treatment of infections caused by Mycobacterium tuberculosis, M. avium-intracellulare complex, rapidly growing mycobacteria and M. leprae, and deserve consideration as part of a multi-drug regimen in otherwise untreatable mycobacterial infections. Clinical data regarding fluoroquinolone monotherapy in brucellosis indicate unacceptable failure rates which preclude the use of these agents in this indication. The quinolones have some efficacy in genital chlamydial infections, but may have limitations in this indication also. In conclusion, as a result of the in vitro activity of the quinolones and their favourable pharmacokinetics, these agents are now an important part of the armamentarium against intracellular infections.