The potential role of artificial intelligence in the clinical management of Hansen's disease (leprosy).

Missed and delayed diagnoses of Hansen's disease (HD) are making the battle against it even more complex, increasing its transmission and significantly impacting those affected and their families. This strains public health systems and raises the risk of lifelong impairments and disabilities. Worryingly, the three countries most affected by HD witnessed a growth in new cases in 2022, jeopardizing the World Health Organization's targets to interrupt transmission. Artificial intelligence (AI) can help address these challenges by offering the potential for rapid case detection, customized treatment, and solutions for accessibility challenges-especially in regions with a shortage of trained healthcare professionals. This perspective article explores how AI can significantly impact the clinical management of HD, focusing on therapeutic strategies. AI can help classify cases, ensure multidrug therapy compliance, monitor geographical treatment coverage, and detect adverse drug reactions and antimicrobial resistance. In addition, AI can assist in the early detection of nerve damage, which aids in disability prevention and planning rehabilitation. Incorporating AI into mental health counseling is also a promising contribution to combating the stigma associated with HD. By revolutionizing therapeutic approaches, AI offers a holistic solution to reduce the burden of HD and improve patient outcomes.

Steps towards eliminating Hansen's disease stigma.

Persons affected by Hansen's disease (PAHD) can develop long-term physical disabilities and psychological problems if the disease is not managed promptly and correctly. The complex and multi-faceted nature of stigma related to Hansen's Disease, and the discrimination arising from it, demands multiple parallel steps to improve the health, well-being and lived experience of People Affected by Hansen's Disease, including: 1) adoption and pursuance of a human rights based approach; 2) revocation of discriminatory laws; 3) education and training for healthcare workers; 4) new techniques and therapies to diagnose and treat HD without side-effects and to reduce risk of disabilities; 5) elimination of stigmatising terminology.

Systematic Review of Hansen Disease Attributed to Mycobacterium lepromatosis.

In 2008, bacilli from 2 Hansen disease (leprosy) cases were identified as a new species, Mycobacterium lepromatosis. We conducted a systematic review of studies investigating M. lepromatosis as a cause of HD. Twenty-one case reports described 27 patients with PCR-confirmed M. lepromatosis infection (6 dual M. leprae/M. lepromatosis): 10 case-patients in the United States (7 originally from Mexico), 6 in Mexico, 3 in the Dominican Republic, 2 each in Singapore and Myanmar, and 1 each in Indonesia, Paraguay, Cuba, and Canada. Twelve specimen surveys reported 1,098 PCR-positive findings from 1,428 specimens, including M. lepromatosis in 44.9% (133/296) from Mexico, 3.8% (5/133) in Colombia, 12.5% (10/80) in Brazil, and 0.9% (2/224) from the Asia-Pacific region. Biases toward investigating M. lepromatosis as an agent in cases of diffuse lepromatous leprosy or from Mesoamerica precluded conclusions about clinicopathologic manifestations and geographic distribution. Current multidrug treatments seem effective for this infection.

Clinical and radiological evaluation of maxillofacial and otorhinolaryngological manifestations of Hansen's disease.

To characterize maxillofacial, otorhinolaryngological and oral manifestations of Hansen's disease (HD), we conducted a cross-sectional study in 21 current patients attending the Unidade Básica de Saúde de Jardim América, Espírito Santo, Brazil and 16 former patients resident at Pedro Fontes Hospital using data from computed tomography imaging, rhinoscopy, and oroscopy. Maxillofacial characteristics were compared with 37 controls. Differences in bone alterations across the three groups were determined mainly by severe resorption/atrophy being more frequent in former HD patients, with severe resorption/atrophy of the anterior alveolar process of maxilla in 50.0% (8/16) of former patients, 28.6% (6/21) of current patients and 10.8% (4/37) of controls and of nasal bones and aperture in 31.3% (5/16) of former patients compared with 0/21 current patients and two controls. There were no substantial differences in otorhinolaryngological and oroscopic findings between the two patient groups. HD patients had more tooth loss than the age-matched control group. Maxillofacial, otorhinolaryngological and oroscopic finding scores were strongly correlated only in current HD patients. Correlation between otorhinolaryngological and maxillofacial scores suggests that protocols for HD patient assessment and follow-up could include otorhinolaryngological evaluation, with radiological imaging where necessary, subject to replication of our findings in a larger study.

Hansen's disease and COVID-19 co-infection in Brazil.

BACKGROUND: The implications of COVID-19 co-infection in patients under treatment for Hansen's disease (HD, leprosy) remain uncertain. We aimed to describe clinical characteristics, treatments, and outcomes in patients with HD and COVID-19 in Brazil. METHODS: Cross-sectional study recruiting adult HD patients with PCR-confirmed COVID-19 from five HD treatment centers in Brazil between March 1, 2020, and March 31, 2021. At the time of this study, no patient had received COVID-19 vaccine. RESULTS: Of 1377 patients under treatment for HD, 70 (5.1%) were diagnosed with COVID-19. Of these, 41 (58.6%) had PCR-confirmed COVID-19, comprising 19 men and 22 women, aged 24-67 (median 45) years. HD was multibacillary in 39/41 patients. Eight patients ceased WHO Multi-Drug Therapy for HD, three for lack of drugs, two because of COVID-19, and three for other reasons. Of the 33 who continued treatment, 26 were on the standard regimen and seven an alternative regimen. Seventeen patients were receiving oral prednisone, including nine patients with type 1 reaction, four with type 2 reaction, three with neuritis, and one with rheumatologic disease. Twelve patients were hospitalized for COVID-19, and six patients died, of whom three had hypertension and one also had type 2 diabetes and obesity. CONCLUSIONS: COVID-19 and Hansen's disease co-infection did not appear to change the clinical picture of either disease in this cross-sectional study. The wider impact of the pandemic on persons affected by HD requires follow-up and monitoring.

Clinical and radiological assessment of rhinomaxillary syndrome in Hansen's disease.

Background More than four million people today live with Hansen's disease, and 200,000 new cases are diagnosed every year. Lifetime effects of Hansen's disease manifest as changes to bones of the face, hands and feet, resulting in physical impairment, secondary complications and facial changes that can be detrimental to quality of life, particularly among the elderly. Aims This study aimed to perform a detailed characterization of rhinomaxillary syndrome and its clinical manifestations in older persons treated in the past for Hansen's disease. Methods This was a cross-sectional study to characterize rhinomaxillary syndrome among older persons (age 60+ years) resident at Pedro Fontes Hospital, Cariacica, Espírito Santo, Brazil. Computed tomography images were examined with three-dimensional reconstructions to assess alterations to maxillofacial bones according to criteria for radiological rhinomaxillary syndrome. Participants were examined to assess facial alterations according to criteria for clinical rhinomaxillary syndrome. Results Rhinomaxillary syndrome was investigated in 16 participants (ten females and six males), median age 70 (range 60-89) years, age at diagnosis 20 (6-43) years and time since diagnosis 46 (26-70) years. Four participants fully met radiological rhinomaxillary syndrome criteria, four partially. All participants with full radiological rhinomaxillary syndrome presented with facial changes which met criteria for clinical rhinomaxillary syndrome, including "saddle nose" (loss of nasal dorsal height and shortened length of nose, due to cartilaginous and/or bone collapse), concave middle third of the face with sunken nose, maxillary retrognathia and inverted upper lip. Limitations Clinical histories were incomplete for some participants because records were lost at the hospital over time. Conclusion Until Hansen's disease is eliminated from endemic countries, persons affected will continue to present with rhinomaxillofacial alterations caused by Mycobacterium leprae infection. Clinical protocols for assessment and long-term care need to include otorhinolaryngological evaluation, mainly to prevent secondary complications. When rhinomaxillofacial bone changes are suspected, this evaluation should be supported by computed tomography imaging, if available.

Mycobacterium lepromatosis as a Second Agent of Hansen's Disease.

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.

The influence of leprosy-related clinical and epidemiological variables in the occurrence and severity of COVID-19: A prospective real-world cohort study.

BACKGROUND: Protective effects of Bacillus Calmette-Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19. METHODOLOGY/PRINCIPAL FINDINGS: We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93-13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04-4.06) were significant risk factors for COVID-19. CONCLUSIONS/SIGNIFICANCE: Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.

Consensus in Brazil on the renaming of leprosy to Hansen's disease.

Brazil has been at the forefront in replacing the stigmatising term 'leprosy' with the non-pejorative alternative 'Hansen's disease' ('hanseníase'), with use of the former word prohibited by law since 1995. This change followed decades of advocacy, including by civil society organisations representing people affected by the disease. A survey of people affected by Hansen's disease in Brazil found that 111/112 respondents preferred the alternative term, supporting the view that consideration of non-stigmatising terminology that respects the wishes of people affected by the disease should be part of the WHO Global Leprosy (Hansen's disease) Strategy to achieve 'zero stigma' by 2030.

Zoonotic risk of Hansen's disease from community contact with wild armadillos: A systematic review and meta-analysis.

Understanding and quantifying the risk of Hansen's disease (HD) through zoonotic transmission of Mycobacterium leprae infection from wild armadillos is important because hunting, handling and consumption of these animals is widespread in communities where HD is endemic, posing a potential threat to the health of individuals and to HD elimination. We conducted a systematic review (PROSPERO CRD42019159891) of publications in MEDLINE, EMBASE, Global Health, Scopus, LILACS, Biblioteca Digital Brasileira de Teses e Dissertações, Catálogo de Teses e Dissertações de CAPES, and Biblioteca Virtual em Saúde up to 09/05/2020 using Mesh and text terms in English, Portuguese, Spanish and French. Random effects meta-analyses were performed including of subgroups by endemicity and type of exposure. Seven of the nine included studies were case-control, four from Brazil and three from the USA, comprising 1,124 cases and 2,023 controls in total. The other two studies, one from Brazil and one from Colombia, were cross-sectional. The overall summary estimate (odds ratio, OR) for the relative odds of HD comparing people who had direct contact with armadillos and/or had eaten armadillo meat with those who had not was OR = 2.60 (95% CI 1.78-3.80, p < .001) with a predictive interval of OR = 1.10-6.17. Summary odds ratios for specific exposures were as follows: indirect contact, OR = 1.39 (95% CI 1.02, 1.89) (p = .04); eating, OR = 2.29 (95% CI 1.13, 4.66) (p = .02); hunting, OR = 2.54 (95% CI 1.21, 5.33) (p = .01). Most of the included studies had moderate risk of bias. Crude estimates were reduced by up to 24% when adjusted for confounders (where reported). Direct contact with wild armadillos was strongly associated with an increased risk of HD, whilst evidence for an increased risk of HD from indirect contact was weaker. The fraction of HD in endemic countries attributable to zoonotic transmission from armadillos remains unknown, but the precautionary principle needs to be adopted to protect public health.

Case Report: Leprosy Osteoarticular Alterations Mimicking Rheumatoid Arthritis.

Deformities of bones of the face and extremities are markers of leprosy (Hansen's disease) which contribute to stigma associated with this disease. Among these deformities are articular alterations that can mimic rheumatoid arthritis (RA). In this case, a 64-year-old man presented with a history of having been treated for lepromatous leprosy and erythema nodosum leprosum episodes, which evolved with joint alterations similar to those of RA. Most cases of leprosy-related arthritis are associated with reactional episodes, of which a large number do not respond to conventional therapy for leprosy reactions. In cases of chronic arthritis not associated with leprosy reactions, although patients show considerable relief with anti-leprosy therapy, arthritis is not completely resolved. This emphasizes the need for early diagnosis and treatment of leprosy to prevent the development of osteoarticular alterations.

Prevalence of Mycobacterium leprae in armadillos in Brazil: A systematic review and meta-analysis.

Understanding the prevalence of M. leprae infection in armadillos is important because of evidence from Brazil and other countries of an association between contact with armadillos and the development of Hansen's Disease (leprosy). Our aim was to characterize studies which have investigated natural M. leprae infection in wild armadillos in Brazil, and to quantify and explore variability in the reported prevalence of infection. We conducted a systematic review (PROSPERO CRD42019155277) of publications in MEDLINE, EMBASE, Global Health, Scopus, LILACS, Biblioteca Digital Brasileira de Teses e Dissertações, Catálogo de Teses e Dissertações de CAPES, and Biblioteca Virtual em Saúde up to 10/2019 using Mesh and text search terms (in English, Portuguese, Spanish, and French). The 10 included studies represented a total sample of 302 armadillos comprising 207 (69%) Dasypus novemcinctus, 67 (22%) Euphractus sexcinctus, 16 (5%) Priodontes maximus, 10 (3%) Cabassous unicinctus, and 2 (1%) Cabassous tatouay from 7 different states. Methods used included histopathology (4 studies), PGL-1 and LID-1 antigen detection (4 studies) and examination for clinical signs of disease (4 studies). Eight studies used PCR of which 7 targeted the RLEP repetitive element and 3 tested for inhibitory substances. M. leprae prevalence by PCR ranged from 0% (in 3 studies) to 100% in one study, with a summary estimate of 9.4% (95% CI 0.4% to 73.1%) and a predictive interval of 0-100%. The average prevalence is equivalent to 1 in 10 armadillos in Brazil being infected with M. leprae, but wide variation in sample estimates means that the prevalence in any similar study would be entirely unpredictable. We propose instead that future studies aim to investigate transmission and persistence of M. leprae within and between armadillo populations, meanwhile adopting the precautionary principle to protect human health and an endangered species in Brazil.

Why we should stop using the word leprosy.

Leprosy is endemic in more than 100 countries worldwide, with over 200 000 new diagnoses each year and more than 4 million people living with some form of impairment related to leprosy. The term leprosy, as used in the Bible, designated a multitude of diseases with skin manifestations. Biblical leprosy carried huge stigma and was considered synonymous with impurity and divine punishment. Global actions to eliminate leprosy have been implemented but have yet to succeed, with stigmatisation and discrimination against people affected by the disease being recognised as two of the biggest obstacles. In Brazil, leprosy was officially renamed hanseníase (Hansen's disease) in 1975, and the Brazilian experience of renaming leprosy during the past four decades has given clear signs of the benefit of this measure in fighting stigma and discrimination. More recent actions by WHO and many years of advocacy by patient organisations have followed, but concrete and effective measures to dignify language and terminology need to be implemented as soon as possible.

Leprosy in skulls from the Paris Catacombs.

Background: The Paris Catacombs contain the remains of approximately 6 million people dating back to the 15th century, when leprosy was endemic in France.Aims: The aim of this palaeopathological study was to identify the presence of leprosy in skulls from the Paris Catacombs.Subjects and methods: Macroscopic examination of skulls in situ for bone changes secondary to oronasal soft tissue infection by leprosy. Skulls were categorised as having "probable" signs of leprosy if they had an enlarged nasal (pyriform) aperture, resorption of the anterior nasal spine, and resorption of the alveolar processes of maxilla, and as having "possible" signs of leprosy if they met one of these three criteria.Results: Skulls from 123 sections within the Catacombs (approximately 1500 remains in total) were triaged, with 367 skulls identified as suitable for examination. Of these, 74 had central facial bone alterations/abnormalities and underwent detailed examination, yielding 0.5% (2/367) classified as having probable, and 5.7% (21/367) possible signs of leprosy.Conclusions: The proportion of skulls with probable signs of leprosy gives an approximate estimate (0.5%) for the prevalence of this disease in the population of Paris (or districts of Paris) during the 15-18th centuries.