Clinical aspects of leprosy.

Leprosy is a chronic, infectious disease caused by Mycobacterium leprae. It mainly affects the peripheral nervous system, skin, and certain other tissues such as the reticulo-endothelial system, bones and joints, mucous membranes, eyes, testes, muscles, and adrenals. Leprosy clinical presentation varies from few to widespread lesions. In most patients, early leprosy presents as macular and hypopigmented lesions. This initial clinical presentation is known as indeterminate leprosy and occurs in individuals who have not developed cell-mediated immunity against M. leprae yet. The number of lesions depends on the genetically determined cellular immunity of the patient. Individuals presenting a vigorous cellular immune response and limited humoral immune responses to M. leprae, usually present few skin lesions. Without treatment, those patients tend to evolve into the polar tuberculoid or borderline tuberculoid form of leprosy. Due to the inability to mount an effective cellular-mediated response to M. leprae and the consequent hematogenous spread of the bacilli, some patients may present with numerous and symmetrically distributed hypochromic lesions. Without treatment these patients evolve to a nonresistant form of leprosy, polar lepromatous.

Human genetic susceptibility to intracellular pathogens.

Intracellular pathogens contribute to a significant proportion of infectious disease morbidity and mortality worldwide. Increasing evidence points to a major role for host genetics in explaining inter-individual variation in susceptibility to infectious diseases. A number of monogenic disorders predisposing to infectious disease have been reported, including susceptibility to intracellular pathogens in association with mutations in genes of the interleukin-12/interleukin-23/interferon-γ axis. Common genetic variants have also been demonstrated to regulate susceptibility to intracellular infection, for example the CCR5Δ32 polymorphism that modulates human immunodeficiency virus-1 (HIV-1) disease progression. Genome-wide association study approaches are being increasingly utilized to define genetic variants underlying susceptibility to major infectious diseases. This review focuses on the current state-of-the-art in genetics and genomics as pertains to understanding the genetic contribution to human susceptibility to infectious diseases caused by intracellular pathogens such as tuberculosis, leprosy, HIV-1, hepatitis, and malaria, with a particular emphasis on insights from recent genome-wide approaches. The results from these studies implicate common genetic variants in novel molecular pathways involved in human immunity to specific pathogens.

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...