Molecular epidemiology of leprosy: An update

Avanzi, Charlotte; Singh, Pushpendra; Truman, Richard W.; Suffys, Philip Noël

doi:10.1016/j.meegid.2020.104581

Cited by 38 publications

(31 citation statements)

References 162 publications

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“…The age of all directly dated samples is provided in calibrated CE. The listed SNP types are determined according to the new SNP typing system [ 46 ]. Following this new system, a new SNP was determined for the BEL024 sample (labeled with an asterisk), but according to the SNP typing system by Monot and colleagues [ 42 ] the sample would be classified as 3L Sample Sample age ( 14 C dates: non-italics; archeological ages: italics) Location Mean coverage Coverage ≥ 1× in % Coverage ≥ 3× in % Genotype (new) Branch R7546-671 19th–20th century CE St. Petersburg, Russia 16.51 97.16 94.96 2F 2F UF11 18th century CE Sant Llàtzer, Barcelona, Spain 6.71 85.67 61.80 3I-1 3 UF8 16th century CE Sant Llàtzer, Barcelona, Spain 1.46 67.52 18.99 3I-1 3 UF21 1431–1611 cal CE Sant Llàtzer, Barcelona, Spain 4.11 92.14 67.70 3I-1 3 UF25 1423–1466 cal CE Sant Llàtzer, Barcelona, Spain 33.09 97.40 95.73 3K-0 0 JDS097 1231–1384 cal CE Hospital of St. John, Cambridge, UK 12.81 96.89 94.27 3I-1 3 PAVd’09_I.5 1283–1396 cal CE Valle da Gafaria, Lagos, Portugal 96.82 97.40 97.44 3I-1 3 Bergen 1268–1388 cal CE Nonneseter, Bergen, Norway 110.61 97.45 97.44 3I-1 3 UF700 1035–1165 cal CE …”

Section: Resultsmentioning

confidence: 99%

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes

et al. 2021

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Background Hansen’s disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease’s complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period. Results Here, we reconstructed 19 ancient M. leprae genomes to further investigate M. leprae’s genetic variation in Europe, with a dedicated focus on bacterial genomes from previously unstudied regions (Belarus, Iberia, Russia, Scotland), from multiple sites in a single region (Cambridgeshire, England), and from two Iberian leprosaria. Overall, our data confirm the existence of similar phylogeographic patterns across Europe, including high diversity in leprosaria. Further, we identified a new genotype in Belarus. By doubling the number of complete ancient M. leprae genomes, our results improve our knowledge of the past phylogeography of M. leprae and reveal a particularly high M. leprae diversity in European medieval leprosaria. Conclusions Our findings allow us to detect similar patterns of strain diversity across Europe with branch 3 as the most common branch and the leprosaria as centers for high diversity. The higher resolution of our phylogeny tree also refined our understanding of the interspecies transfer between red squirrels and humans pointing to a late antique/early medieval transmission. Furthermore, with our new estimates on the past population diversity of M. leprae, we gained first insights into the disease’s global history in relation to major historic events such as the Roman expansion or the beginning of the regular transatlantic long distance trade. In summary, our findings highlight how studying ancient M. leprae genomes worldwide improves our understanding of leprosy’s global history and can contribute to current models of M. leprae’s worldwide dissemination, including interspecies transmissions.

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Section: Resultsmentioning

confidence: 99%

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes

et al. 2021

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“…While there does now appear to be consensus that M. lepromatosis is a second causal agent of HD (Sharma et al, 2020), a multitude of questions remain. Most of these can be answered using genomic methods to differentiate M. leprae and M. lepromatosis infection (Avanzi et al, 2020;Sharma et al, 2020). The most important immediate question in terms of public health, human disease burden, and HD prevention and control is the extent of M. lepromatosis infection in HD endemic countries and its contribution to HD incidence.…”

Section: Discussionmentioning

confidence: 99%

“…4. Whole genome sequencing of specimens from animal surveys and surveillance studies in Latin American countries to elucidate strains and determine the relatedness of M. lepromatosis (and M. leprae) in animals and humans (Avanzi et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium lepromatosis as a Second Agent of Hansen’s Disease

Deps

Collin

2021

Front. Microbiol.

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Mycobacterium lepromatosis was identified as a new species and second causal agent of Hansen’s disease (HD, or leprosy) in 2008, 150years after the disease was first attributed to Mycobacterium leprae. M. lepromatosis has been implicated in a small number of HD cases, and clinical aspects of HD caused by M. lepromatosis are poorly characterized. HD is a recognized zoonosis through transmission of M. leprae from armadillos, but the role of M. lepromatosis as a zoonotic agent of HD is unknown. M. lepromatosis was initially associated with diffuse lepromatous leprosy, but subsequent case reports and surveys have linked it to other forms of HD. HD caused by M. lepromatosis has been reported from three endemic countries: Brazil, Myanmar, and Philippines, and three non-endemic countries: Mexico, Malaysia, and United States. Contact with armadillos in Mexico was mentioned in 2/21 M. lepromatosis HD case reports since 2008. M. lepromatosis in animals has been investigated only in non-endemic countries, in squirrels and chipmunks in Europe, white-throated woodrats in Mexico, and armadillos in the United States. To date, there have only been a small number of positive findings in Eurasian red squirrels in Britain and Ireland. A single study of environmental samples found no M. lepromatosis in soil from a Scottish red squirrel habitat. Future studies must focus on endemic countries to determine the true proportion of HD cases caused by M. lepromatosis, and whether viable M. lepromatosis occurs in non-human sources.

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“…Furthermore, the lack of an effective diagnostic procedure makes tracking of M. leprae transmission difficult [4][5][6][7]. The genetic predisposition to early leprosy [8] emphasizes the need for an opportune diagnosis and development of low-cost immunotherapies to reduce leprosy incidence in developed countries [9,10]. The spectrum of clinical manifestations in leprosy correlates with the type of immune response elicited.…”

Section: Introductionmentioning

confidence: 99%

Intramuscular Boosting with hIFN-Alpha 2b Enhances BCGphipps-Induced Protection in a Murine Model of Leprosy

Guerrero

Rangel-Moreno

Islas-Trujillo

et al. 2021

Microbiology Research

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Host immunity to Mycobacterium leprae encompasses a spectrum of mechanisms that range from cellular immunity-driven protection to damage associated with humoral immunity as in type-2 leprosy reactions. Although type I interferons (IFNs) participate in eliminating intracellular pathogens, their contribution to the production of antibodies and CD3+ FOXP3+ regulatory T cells (Tregs) in BCG vaccine-mediated protection in leprosy is unknown. BCGphipps (BCGph) priming followed by intramuscular hIFN-α 2b boost significantly reduced lesion size and Mycobacterium lepraemurium growth in the skin. T follicular regulatory cells (TFR), a subset of Tregs induced by immunization or infection, reside in the germinal centers (GCs) and modulate antibody production. We found impaired Treg induction and improved GCs in draining lymph nodes of BCGph primed and hIFN-α 2b boosted mice. Moreover, these mice elicited significant amounts of IL-4 and IL-10 in serum. Thus, our results support the adjuvant properties of hIFN-α 2b in the context of BCGph priming to enhance protective immunity against skin leprosy.

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Molecular epidemiology of leprosy: An update

Cited by 38 publications

References 162 publications

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes

Mycobacterium lepromatosis as a Second Agent of Hansen’s Disease

Intramuscular Boosting with hIFN-Alpha 2b Enhances BCGphipps-Induced Protection in a Murine Model of Leprosy

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