Table 2.

A potential research and policy roadmap to reduce leprosy transmission

Categories	Key considerations	Suggestions
Understanding pathogenic mycobacterial ecosystems	M. tuberculosis complex, M. leprae and M. ulcerans are phylogenetically closely related These three pathogenic species cause three major diseases: tuberculosis, leprosy, and Buruli ulcer, respectively Mycobacterium ulcerans transmission cycle involves aquatic insect vectors, aquatic plants, and aquatic animals. Buruli ulcer is transmitted by aquatic fleas (Naucoridae) Insect vectors or plants may have played a role in much earlier transmission of tuberculosis to humans that that occurring during the neolithic revolution, where the disease spread likely from human to human and from humans to domesticated dairy animals Armadillos are responsible for the majority of autochthonous cases of human leprosy in the Southeast USA	Further studies to address zoonotic transmission by armadillos in Latin America Assess the role of armadillo control strategies to reduce leprosy transmission Potential role for household-insecticide spraying or other vector-prevention or vector-control strategies for vector control among patients diagnosed with multibacillary leprosy
Epidemiological clues linked to historical population migration events	There are important associations between the spread of leprosy to migration patterns of earlier human societies and trade routes (i.e., the Silk Road that United Europe to China contributed to the spread of leprosy); or to historical events corresponding to the returning expeditionary forces of antiquity spreading the pathogen from the Middle-Eastern strain of M. leprae to Medieval Europe Subsequently, European explorers spread the disease westward to the New World and through the Atlantic Slave Trade	Evaluate transmission networks Historical reassessments of important population migrations to identify potentially missed epidemiologic clues
Early diagnosis, treatment and prevention of neurologic disability	Early identification of subclinical cases may assist in interrupting the course of the natural history of the disease by preventing the occurrence of clinical manifestations including and its associated nerve injury; and from a public health perspective to potentially decrease spillage of M. leprae by instituting chemophrophylaxis of contacts; treatment of those with latent infection; or preemptive treatment of those with subclinical disease	Epidemiologic mapping of hot zones of transmission Rigorous contact investigation of patients with leprosy Development of a diagnostic test for early-stage or subclinical infectiona Early identification of leprosy cases in endemic areas through school-based surveys Implement post-exposure treatment of contacts, latent infection, or subclinical infection (chemoprophylaxis versus latent treatment versus preemptive treatment)
Preventing leprosy reactions	Leprosy reactions may occur during multi-drug therapy (MDT) or even after completing MDT Leprosy reactions are often precipitated by stress (e.g., surgery, infections, trauma) or after the initiation of MDT Herpes viruses reactive in the human host during stress Leprosy reactions exacerbate peripheral nerve injury and therefore may lead to neurologic sequelae Herpes viruses have host immunomodulatory properties and there is increasing evidence that the reactivation of some herpes viruses is responsible for drug reactions (i.e., Epstein-Barr virus (EBV) infection reaction to amoxicillin during an episode of infectious mononucleosis; or herpes human virus 6 reactivation linked to drug reaction eosinophilic systemic syndrome (HHV-6); or cytomegalovirus (CMV) causing immunologic rejection in transplant recipients	Early diagnosis of leprosy cases Close clinical follow-up of patients initiating MDT Long-term period follow up of patients that completed MDT, particularly those with borderline and lepromatous forms of leprosy Effective management of leprosy reactions to prevent further nerve injury Research to confirm the association between herpes viruses and the occurrence of leprosy reactions: evaluate patients presenting with newly diagnosed leprosy reactions with molecular testing (i.e., PCR) for herpes virus reactivation including HHV-6, Epstein-Barr virus, Varicella-Zoster virus, cytomegalovirus or others Evaluate the potential role for the institution of antiviral suppressive therapy among those with evidence of herpes virus reactivation

^a Mycobacterium leprae has the ability to reprogram the Schwann cell into a stem-cell-like cell that carries the bacilli into other tissues to ensure its dissemination. Given this systemic dissemination it seems feasible to search for the development of assays such as an interferon—assay employing a similar approach to the one used for detection of cytokine-production patterns by M. tuberculosis