26.2 Bacterial diseases of the nervous system  (Page 11/20)

In the human body, M. leprae grows best at the cooler temperatures found in peripheral tissues like the nose, toes, fingers, and ears. Some of the virulence factors that contribute to M. leprae ’s pathogenicity are located on the capsule and cell wall of the bacterium. These virulence factors enable it to bind to and invade Schwann cells , resulting in progressive demyelination that gradually destroys neurons of the PNS. The loss of neuronal function leads to hypoesthesia (numbness) in infected lesions. M. leprae is readily phagocytized by macrophages but is able to survive within macrophages in part by neutralizing reactive oxygen species produced in the oxidative burst of the phagolysosome. Like L. monocytogenes , M. leprae also can move directly between macrophages to avoid clearance by immune factors.

The extent of the disease is related to the immune response of the patient. Initial symptoms may not appear for as long as 2 to 5 years after infection. These often begin with small, blanched, numb areas of the skin. In most individuals, these will resolve spontaneously, but some cases may progress to a more serious form of the disease. Tuberculoid (paucibacillary) Hansen’s disease is marked by the presence of relatively few (three or less) flat, blanched skin lesions with small nodules at the edges and few bacteria present in the lesion. Although these lesions can persist for years or decades, the bacteria are held in check by an effective immune response including cell-mediated cytotoxicity . Individuals who are unable to contain the infection may later develop lepromatous (multibacillary) Hansen’s disease . This is a progressive form of the disease characterized by nodules filled with acid-fast bacilli and macrophages. Impaired function of infected Schwann cells leads to peripheral nerve damage, resulting in sensory loss that leads to ulcers, deformities, and fractures. Damage to the ulnar nerve (in the wrist) by M. leprae is one of the most common causes of crippling of the hand. In some cases, chronic tissue damage can ultimately lead to loss of fingers or toes. When mucosal tissues are also involved, disfiguring lesions of the nose and face can also occur ( [link] ).

Hansen’s disease is diagnosed on the basis of clinical signs and symptoms of the disease, and confirmed by the presence of acid-fast bacilli on skin smears or in skin biopsy specimens ( [link] ). M. leprae does not grow in vitro on any known laboratory media, but it can be identified by culturing in vivo in the footpads of laboratory mice or armadillos. Where needed, PCR and genotyping of M. leprae DNA in infected human tissue may be performed for diagnosis and epidemiology.

Hansen’s disease responds well to treatment and, if diagnosed and treated early, does not cause disability. In the United States, most patients with Hansen’s disease are treated in ambulatory care clinics in major cities by the National Hansen’s Disease program, the only institution in the United States exclusively devoted to Hansen’s disease. Since 1995, WHO has made multidrug therapy for Hansen’s disease available free of charge to all patients worldwide. As a result, global prevalence of Hansen’s disease has declined from about 5.2 million cases in 1985 to roughly 176,000 in 2014. World Health Organization, “Leprosy Fact Sheet,” 2016. Accessed September 13, 2016. http://www.who.int/mediacentre/factsheets/fs101/en/. Multidrug therapy consists of dapsone and rifampicin for all patients and a third drug, clofazimin , for patients with multibacillary disease.