Leprosy: Evidence supporting safe diagnosis and monitoring of contacts
Authors: Silvana Margarida Benevides Ferreira1,3, Fabiane Verônica da Silva 1, Juliana Salomão Rocha de Oliveira2, Juliana Akie Takahashi2,3, Maristela Santini Martins2,3
1. Federal University of Mato Grosso (UFMT), Graduate Program in Nursing, Cuiabá, MT, Brazil.
2. University of São Paulo (USP), School of Nursing, São Paulo, SP, Brazil.
3. Brazilian Centre for Evidence-Based Health Care: JBI Centre of Excellence, São Paulo, Brazil.
Introduction
The COVID-19 pandemic affected the quality of health services worldwide, but it also boosted scientific research aimed at strengthening sustainable health initiatives. In the context of leprosy, this translates into the search for evidence to ensure safety in diagnosing and monitoring patient contacts. In 2021, we published an article titled "Post-exposure prophylaxis with single-dose rifampicin: From evidence to World Health Organization (WHO) guidelines," based on a systematic review published in JBI Evidence Synthesis (Ferreira et al. 2017). Today, we revisit leprosy as an ancient and neglected disease, addressing the question: can we count on evidence to support the safety of diagnosis and monitoring of contacts with the disease? We need to join forces to meet the health needs of people with leprosy, especially in countries with the highest disease burden (WHO 2024). Leprosy is a chronic, transmissible disease with high disabling potential, caused by infection with Mycobacterium leprae (M. leprae). Early detection and safe diagnosis, along with contact surveillance, are priorities—particularly in countries with a high disease burden, such as India and Brazil (WHO 2024). The WHO recommends single-dose rifampicin (SDR) prophylaxis for contacts, aiming to eliminate leprosy as a public health problem (Ferreira et al. 2017; WHO 2018).
Social inequalities can determine the persistence of leprosy and create difficulties in controlling the disease, as well as other neglected diseases. This emphasizes the predominance of leprosy in regions with high socio-economic vulnerability, where access to health services and other essential services is poor. Poverty is a determining factor for the occurrence and transmission of leprosy, and variables such as poor living conditions; lack of access to public services such as sanitation, waste collection, and safe drinking water; and lack of hygiene are commonly present among cases. In light of this, it is clear that strategies to control leprosy must be intersectoral ( Cardoso et al. 2023; Jesus et al. 2023; Santos et al. 2019).
Intersectorality between health and social policies regarding populations affected by leprosy is essential to meet the goals outlined in the Global Strategy for a World Free of Leprosy. In Brazil, the Interministerial Committee for the Elimination of Tuberculosis, Leprosy, and Other Socially Determined Diseases (Ciedds) was established through Decree No. 11,494 in April 2023. Coordinated by the Ministry of Health, the strategy articulates intersectoral public policies aimed at health. The strategy involves nine other ministries and aims to achieve health equity and reduce social inequalities, which are directly linked to the causes of diseases that more severely affect populations with higher social vulnerability (Ministry of Health 2024).
Evidence shows that biomarkers with higher bacillary loads in leprosy patients are associated with a greater risk of illness. Rapid and accurate diagnosis is critical for the formulation of effective public policies for disease control and contact surveillance ( Espinosa et al. 2018; Gama et al. 2019; Penna et al. 2016; Steinman et al. 2017). Household contacts of leprosy patients have nearly four times the risk of developing the disease compared with the general population, especially children, who are more exposed to illness (Moet et al. 2006; Rodrigues et al. 2020).
The WHO has set three basic criteria for the diagnosis of leprosy: (1) hypopigmented or reddish skin patches with loss of sensation; (2) thickening or enlargement of peripheral nerves with loss of sensation and/or muscle weakness; and (3) the presence of acid-fast bacilli (AFB) in skin smears. When these criteria are met, the accuracy of the diagnosis can reach up to 95%, contrasting with inadequate or delayed diagnoses, which may perpetuate disease transmission, especially among household contacts (Huang, Su & Chen, 2023; WHO, 2018).
The problem
Although leprosy is predominantly diagnosed based on clinical criteria, its clinical and epidemiological manifestations are broad, presenting a significant challenge for health professionals in terms of effective diagnosis and treatment. This highlights the need for laboratory support to complement clinical findings, both for new cases and relapses, as relapse is an indicator of multidrug therapy efficacy. The persistence of the disease in the community is linked not only to aspects of early diagnosis and treatment but also to the socio-economic conditions to which the population is exposed, which favor re-exposure to the bacillus and the occurrence of multidrug-resistant bacilli. This presents an intersectoral challenge, with greater complexity in its resolution.
The search for answers
Currently, there are advances in the development of tests that assist in diagnosis and contact surveillance, such as the rapid IgM antibody test, real-time polymerase chain reaction (RT-PCR), and serological tests such as Phenolic Glycolipid-I (PGL-1) and leprosy IDRI diagnostic-1 (LID-1). These tests are important for identifying individuals at higher risk of contracting the disease and are significant strategies for contact surveillance and early diagnosis of leprosy. Studies in molecular diagnosis have shown promising results, such as the use of quantitative real-time PCR (qPCR) to improve detection in difficult-to-diagnose cases, such as pure neural leprosy or indeterminate paucibacillary leprosy. Immunological studies have also identified protective factors and greater sensitivity in the preclinical phase with PGL-1 and LID-1 tests, especially when combined with heme oxygenase 1 (HO-1) and arginase 1 ( Espinosa et al. 2018; Gama et al. 2019; Manta et al. 2022; Penna et al. 2016; Prata et al. 2022; Steinman et al. 2017).
With the aim of providing robust evidence to support good clinical practices, we are developing a project funded by the National Council for Scientific and Technological Development (CNPq) of Brazil (Universal call for funding/2023). The project, titled "Biomarkers of Mycobacterium leprae infection in the prediction and protection of new cases of leprosy among household contacts," is linked to the PhD program in Nursing at the School of Nursing, Federal University of Mato Grosso (UFMT). The project is run by Professor Silvana Margarida Benevides Ferreira and involves collaboration with the leprosy laboratory at FIOCRUZ and the School of Nursing, University of São Paulo.
Right diagnosis, safe patient
September 17 is World Patient Safety Day. Every year, the World Health Organization sets a theme for the day. In 2024, the theme is “Improving diagnosis for patient safety” and the campaign slogan is “Get it right, make it safe!”
In the context of leprosy, correct and timely diagnosis is critical to ensuring patient safety and improving health outcomes. An accurate diagnosis identifies the patient’s health problem and is essential for access to appropriate and timely care and treatment. Errors in leprosy diagnosis, such as delayed, incorrect, or missed diagnoses, or failure to communicate the diagnosis to the patient, can lead to serious consequences, perpetuating disease transmission and increasing the risk of disability (WHO 2024b).
Diagnostic safety in leprosy can be significantly improved by addressing the systems-based issues and cognitive factors that contribute to diagnostic errors. Systemic factors include communication failures among health care professionals and between professionals and patients, as well as work overload and ineffective teamwork. Cognitive factors include clinician training and experience, as well as biases, fatigue, and stress, which can negatively affect diagnosis. Addressing these challenges is crucial for the safe and timely diagnosis of leprosy, especially in endemic areas where contact surveillance and early treatment are essential to interrupt disease transmission and improve patients’ quality of life (WHO 2024b).
Intersectoral actions are also crucial for improving diagnostic safety in leprosy by addressing systemic challenges beyond health care settings. Factors such as public education, social determinants of health, workplace conditions, and legal frameworks play a vital role in ensuring timely and accurate diagnosis. Collaboration between sectors such as education, housing, labor, and government is essential to reduce stigma, encourage early health-seeking behavior, and improve access to health care. Community engagement and policy support further enhance diagnostic efforts, particularly in endemic areas, where these actions can significantly reduce disease transmission and improve patient outcomes.
Potential global impact
Ensuring the diagnostic safety of leprosy cases and contacts will allow us to break the cycle of active bacilli transmission in the community. This will enable contact immunoprophylaxis and early treatment at the onset of symptoms, reducing the costs of prolonged, incorrect treatments and the sequelae of late treatment. Additionally, it will contribute to more effective and assertive public policies, improving patients' quality of life and reducing the social stigma associated with the disease.
Alongside the strategies for early diagnosis and treatment of leprosy, it is essential to develop social initiatives to disseminate information about the disease across various sectors of society (such as awareness campaigns in schools, businesses, community meetings, churches, etc.). This helps to dispel misconceptions, considering that social stigma predominantly arises from misinformation about the modes of transmission of the disease.
Challenges and lessons learned
The determinants of the infection and illness process of leprosy can be incorporated into predictive models. However, it is crucial to develop not only diagnostic tests but also to establish standards for serological re-evaluations. It is essential to train health care professionals in the use and interpretation of these tests, integrating them with other contact follow-up strategies. This approach will enhance surveillance and the effectiveness of primary health care services, especially in high-endemicity areas.
Next steps
The next steps for ensuring the safe diagnosis of leprosy include improving education for health care teams to equip professionals with the skills for early detection, accurate diagnosis, and humanized care, all of which improve health outcomes. Humanized care should focus on treating patients with empathy, respect, and consideration of their individual needs, ensuring clear communication, and involving them in health decisions.
Encouraging active patient participation is essential, and health care service managers must create spaces for health education, promote self-care, and ensure discriminatory practices are addressed to foster an inclusive care environment. Strengthening the health care network is also vital, integrating pharmaceutical and laboratory services with health surveillance to enhance patient safety. To overcome social stigma, public education campaigns should be implemented to challenge misconceptions and promote a discrimination-free health care setting. Lastly, cross-sector collaboration, involving partnerships with education and social services, will be crucial in integrating resources and delivering effective, inclusive care.
References
Cardoso, G. C. P. , Santos, E. M., Oliveira, E. A., Abreu, M. A, Souza, M. S., Soares, B. C., & Coriolano, C. R. F. (2023). Capacitação para o controle da hanseníase: avaliação e contribuições para a gestão. Saúde Em Debate, 47(137), 90-100.
da Silva Prata, R. B., Mendes, M. A., Soares, V. C., França-Costa, J., Sales, A. M., Duppré, N. C., de Matos Borges, V., da Silva, T. P., Bozza, P. T., Bozza, M. T., Sarno, E. N., Moraes, M. O., Sperandio da Silva, G. M., & Pinheiro, R. O. (2022). Arginase 1 is a marker of protection against illness in contacts of leprosy patients. Scientific Reports, 12(1), 7850. https://doi.org/10.1038/s41598-022-11944-9
Espinosa, O. A., Benevides Ferreira, S. M., Longhi Palacio, F. G., Cortela, D. D. C.B., & Ignotti, E. (2018). Accuracy of Enzyme-Linked Immunosorbent Assays (ELISAs) in detecting antibodies against Mycobacterium leprae in leprosy patients: A systematic review and meta-analysis. Canadian Journal of Infectious Diseases and Medical Microbiology, 9828023. doi: 10.1155/2018/9828023.
Ferreira, S. M. B., Yonekura, T., Ignotti, E., Oliveira, L. B., Takahashi, J., & Soares, C. B. (2017). Effectiveness of rifampicin chemoprophylaxis in preventing leprosy in patient contacts: a systematic review of quantitative and qualitative evidence. JBI Database of Systematic Reviews and Implementation Reports, 15(10), 2555–2584. https://doi.org/10.11124/JBISRIR-2016-003301
Gama, R. S., Souza, M. L. M., Sarno, E. N., Moraes, M. O., Gonçalves, A., Stefani, M. M. A., Garcia, R. M. G., & Fraga, L. A. O. (2019). A novel integrated molecular and serological analysis method to predict new cases of leprosy amongst household contacts. PLoS Neglected Tropical Diseases, 13(6), e0007400. https://doi.org/10.1371/journal.pntd.0007400
Huang, C. Y., Su, S. B., Chen, & K.T. (2023). An update of the diagnosis, treatment, and prevention of leprosy: a narrative review. Journal of Microbiology and Immunological Infections, 56(1), 1-10. doi:10.1016/j.jmii.2022.01.011
Jesus, I. L. R., Montagner, M. I., Montagner, M. Â., Alves, S. M. C., & Delduque, M. C. (2023). Hanseníase e vulnerabilidade: uma revisão de escopo. Ciênc Saúde Coletiva, 28(1), 143-154.
Ministério da Saúde (BR). Boletim Epidemiológico: Hanseníase. Brasília, DF: Ministério da Saúde; 2024. Número Especial, 22 Jan. 2024.
Moet, F. J., Pahan, D., Schuring, R. P., Oskam, L., & Richardus, J. H. (2006). Physical distance, genetic relationship, age, and leprosy classification are independent risk factors for leprosy in contacts of patients with leprosy. The Journal of Infectious Diseases, 193(3), 346–353. https://doi.org/10.1086/499278
Manta, F. S. N., Jacomasso, T., Rampazzo, R. C. P., Moreira, S. J. M., Zahra, N. M., Cole, S. T., Avanzi, C., Leal-Calvo, T., Vasconcellos, S. E. G., Suffys, P., Ribeiro-Alves, M., Krieger, M. A., Costa, A. D. T., & Moraes, M. O. (2022). Development and validation of a multiplex real-time qPCR assay using GMP-grade reagents for leprosy diagnosis. PLoS Neglected Tropical Diseases, 16(2), e0009850. https://doi.org/10.1371/journal.pntd.0009850
Penna, M. L., Penna, G. O., Iglesias, P. C., Natal, S., & Rodrigues, L. C. (2016). Anti-PGL-1 Positivity as a Risk Marker for the Development of Leprosy among Contacts of Leprosy Cases: Systematic Review and Meta-analysis. PLoS Neglected Tropical Diseases, 10(5), e0004703. https://doi.org/10.1371/journal.pntd.0004703
Rodrigues, T. S. V., Gomes, L. C., Cortela, D. C. B., Silva, E. A., Silva, C. A. L., & Ferreira, S. M. B. (2020). Factors associated with leprosy in children contacts of notified adults in an endemic region of Midwest Brazil. Jornal de Pediatria, 96(5), 593–599. https://doi.org/10.1016/j.jped.2019.04.004
Santos, K. C. B. dos ., Corrêa, R. da G. C. F., Rolim, I. L. T. P., Pascoal, L. M., & Ferreira, A. G. N. (2019). Estratégias de controle e vigilância de contatos de hanseníase: revisão integrativa. Saúde Em Debate, 43(121), 576–591. https://doi.org/10.1590/0103-1104201912122
Steinman, H. M. et al. (2017). Strategies for the interruption of disease transmission and care for infected individuals: early detection and accurate diagnosis. Infectious Disease Reports, 9(2), 65-73.
World Health Organization. Department of Control of Neglected Tropical Diseases. (2018). Guidelines for the diagnosis, treatment and prevention of leprosy. New Delhi, WHO.
World Health Organization. Global leprosy update, 2023: reducing the disease burden. https://www.who.int/publications/i/item/wer-9909-95-104.
World Health Organization. World Patient Safety Day, 17 September 2024: “Improving diagnosis for patient safety”. https://www.who.int/news-room/events/detail/2024/09/17/default-calendar/world-patient-safety-day-17-september-2024-improving-diagnosis-for-patient-safety.
To link to this article - DOI: https://doi.org/10.70253/ICMI3809
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