Leprosy Mailing List – March 25, 2025
Ref.: (LML) Kindness as a key ingredient of HD control
From: Joel Almeida, Mumbai, India
Dear Pieter and colleagues,
It turns out that household incomes in Maranhão, Brazil, increased dramatically from 2022 onwards. This was accompanied by reported declines in the annual rate of newly detected LL (lepromatous) HD (leprosy) with G2D (visible deformity at diagnosis). (Ministry of Health, Brazil) Programs such as Bolsa Familia and Fome Zero in Brazil tend to decrease nutritional deficiencies. Otherwise Vit D deficiency can reduce the likelihood of safe self-healing .
There are many ingredients of effective HD control and care. Kindness is usually not mentioned in guidelines. However, most people value kindness, especially if it is shown towards themselves. In the case of exemplars such as Jozef Damien de Veuster, kindness is deeply valued by many because it was shown towards others (persons who experience(d) HD).
Brazil is not alone in respecting people at the bottom of the heap. Several endemic countries do so. What happens when kindness and respect become drivers of public policy? Maranhão offers some clues.
People in Maranhão do not necessarily have the best training in Brazil. They do not necessarily have the most advanced technology. They certainly do not have the highest incomes. All that needs to keep improving. Despite the room for improvement, they managed to decrease the reported new case detection rate of LL HD with G2D steadily during 2021 to 2023. That suggests steadily fewer LL HD patients had delayed diagnosis. This implies a steady reduction in an important source of astronomical numbers of viable bacilli, given the importance of the nasal mucosa in LL HD. (1) Also, the reported percentage of newly diagnosed HD patients with G2D decreased between 2023 and 2024, suggesting more intensive case-finding in 2024.
Despite all the more intensive case-finding in 2024 than in 2023, 17% fewer HD cases (all classifications) were found in 2024 compared to 2023, and 28% fewer child HD cases. Even though these figures might be updated, this could turn out to be the start of a beneficial trend. That is because new LL HD with G2D is one of the most important predictors of the subsequent incidence rate of HD.
Maranhão, despite its promising outcomes, still shows an increase in recurrent HD. This is a threat. Genomically susceptible LL HD persons who were previously treated can again become a major source of viable bacilli. Once recurrence and reinfection are reduced to negligible levels by kinder and more enlightened case management policies, there is every chance that the 2021-2023 decrease of LL HD G2D in Maranhão will ripen into a relentless decline in the incidence rate of all HD. Such sustained achievement, not inconceivable, could match the rapid decline of HD achieved in Malta, Weifang/Shandong (China), Karigiri (India), Pakistan, Thailand, Vietnam, Ecuador etc. HD and its deforming sequelae are an important cause of destitution. The sustained decline of HD in low-income states such as Maranhão therefore would be particularly beneficial. Maranhão shows what is possible despite all the known disadvantages.
Brazilian science is a world leader in HD. It is fitting that kindness in public policy, alongside this scientific leadership, is producing world-leading declines in the endemicity of HD. How can Maranhão further improve its clinical and epidemiological impact? According to the data, the typical person with newly diagnosed LL HD and G2D (visible deformity) in Maranhão is an adult male with no more than 4 years of schooling,. Men with little or no schooling probably deserve the most focus. Fortunately, in untreated LL HD bacilloscopy of skin smears or nasal smears tends to show astronomical numbers of bacilli. That permits prompt diagnosis especially in high-endemic neighbourhoods or workplaces. These bacilli are the main driver of the endemic. Finding these persons before they develop visible deformity and ensuring good treatment and respectful case management is not only kind to them, but also can switch off a major source of concentrated viable bacilli.
A brief burst of anti-microbials is far from kind. The opportunity for safe self-healing is removed. That is because anti-microbials can activate surviving dormant bacilli in perineural macrophages, release TR9 ligands leading to a cytokines storm, remove the helpful anti-apoptotic effect of live M. leprae, reduce the helpful secretion of insulin-like growth factor-1 by macrophages, switch off the diversion by live M. leprae of host citrate to lipid synthesis within macrophages which otherwise helpfully reduces host mitochondrial membrane potential and damaging reactive oxygen species etc. (2-9) Most of this important knowledge comes from world-leading Brazilian research. Only a full course of anti-microbials with regular nerve function monitoring and good case management can adequately protect the recipient's nerves, limbs and eyes once the opportunity for safe self-healing is removed by giving a dose of anti-microbials to an infected contact. Fortunately Brazil has independent policies that are both scientifically enlightened and kind.
Without kindness, everything can fall apart. Even the Universal Declaration of Human Rights (UDHR) at its heart is based on respect and kindness: "Whereas disregard and contempt for human rights have resulted in barbarous acts which have outraged the conscience of mankind ...". (from preamble to UDHR) Wherever human rights are disregarded, needless suffering can be inflicted on persons who experience(d) HD and their family members. That was not the approach of Jozef Damien de Veuster, and it need not be our approach.
At the level of the individual patient and individual health worker we have many heroes and heroines who demonstrate kindness. May their number grow.
With all sincerity,
Joel Almeida
REFERENCES
1. Davey TF, Rees RJ. The nasal dicharge in leprosy: clinical and bacteriological aspects. Lepr Rev. 1974 Jun;45(2):121-34.
2. Medeiros RCA, Girardi KdCdV, Cardoso FKL et al. Subversion of Schwann Cell Glucose Metabolism by Mycobacterium leprae. J Biol Chem. 2016 Aug 23;291(41):21375–21387. doi:10.1074/jbc.M116.725283
3. Rodrigues LS, da Silva Maeda E, Moreira ME et al. Mycobacterium leprae induces insulin-like growth factor and promotes survival of Schwann cells upon serum withdrawal. Cell.Microbiol. (2010) 12: 42–54
4. Souza BJd, Mendes MA, Sperandio da Silva GM et al. Gene Expression Profile of Mycobacterium leprae Contribution in the Pathology of Leprosy Neuropathy. Front. Med. (2022) 9:861586. doi: 10.3389/fmed.2022.861586
5. Salgado CG, Pinto P, Bouth RC, Gobbo AR, Messias ACC, Sandoval TV et al. miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology. Front Immunol. (2018) 9:463. doi: 10.3389/fimmu.2018.00463. PMID: 29593724; PMCID: PMC5854644.
6. Machado D, Lecorche E, Mougari F et al. Insights on Mycobacterium leprae Efflux Pumps and Their Implications in Drug Resistance and Virulence. Front. Microbiol. (2018) 9:3072. doi: 10.3389/fmicb.2018.03072
7. Madigan CA, Cambier CJ, Kelly-Scumpia et al. A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy. Cell (2017) 170(5):973-985. e10. doi: 10.1016/j.cell.2017.07.030.
8. Dias AA, Silva CO, Santos JPS, Batista-Silva LR, Acosta CCD, Fontes ANB, et al. DNA sensing via TLR-9 constitutes a major innate immunity pathway activated during erythema nodosum leprosum. J Immunol (2016) 197:1905–13. 10.4049/jimmunol.1600042
9. Brugger LMdO, Monnerat M, dos Santos L, Lara FA, Mietto BS. What happens when Schwann cells are exposed to Mycobacterium leprae - A systematic review. IBRO Neuroscience Reports. (2023) 15:11-16
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LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << editorlml@gmail.com
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