Leprosy Mailing List – August 10, 2020
Ref.: (LML) a change in our thinking about the disease leprosy and its epidemiology
From: Ben Naafs, Munnekeburen, the Netherlands
Dear Pieter,
Recently I noticed several papers indicating that at last a change in our thinking about the disease leprosy and its epidemiology is unfolding. I will just cite:
From the group of Maria Cristina Vidal Pessolani: Cristiana Santos de Macedo et al Version 1. F1000Res. 2020; 9: F1000 Faculty Rev-70. Published online 2020 Jan 31. doi: 10.12688/f1000research.21383 New insights into the pathogenesis of leprosy: contribution of subversion of host cell metabolism to bacterial persistence, disease progression, and transmission.
"Chronic infection by the obligate intracellular pathogen Mycobacterium leprae may lead to the development of leprosy. Of note, in the lepromatous clinical form of the disease, failure of the immune system to constrain infection allows the pathogen to reproduce to very high numbers with minimal clinical signs, favouring transmission. The bacillus can modulate cellular metabolism to support its survival, and these changes directly influence immune responses, leading to host tolerance, permanent disease, and dissemination. Among the metabolic changes, upregulation of cholesterol, phospholipids, and fatty acid biosynthesis is particularly important, as it leads to lipid accumulation in the host cells (macrophages and Schwann cells)".
From the group of Claudio Guedes Salgado: Pablo Pinto et al : Scientific Reports | (2020) 10:12648 | https://doi.org/10.1038/s41598-020-69355-7 Leprosy piRnome: exploring new possibilities for an old disease.
". piRNAs function in transposon silencing, epigenetic regulation, and germline development. The functional role of piRNAs and their associated PIWI proteins have started to emerge in the development of human cancers and viral infections, but their relevance to bacterial diseases has not been investigated. The present study reports the piRNome of human skin, revealing that all but one of the piRNAs examined are downregulated in leprosy skin lesions. Considering that one of the best characterized functions of piRNAs in humans is posttranscriptional mRNA silencing, their functions are similar to what we have described for miRNAs, including acting on apoptosis, M. leprae recognition and engulfment, Schwann cell (SC) demyelination, epithelial–mesenchymal transition (EMT), loss of sensation and neuropathic pain".
Adriaty D, Rosita SP C, Iswahyudi , et al. Infectious Disease Reports. PAGEPress Publications. 2020; 12 (S1) : 8748. Leprosy transmission in endemic and non-endemic areas based on the profile of antibody response of PGL-1 and PCR detection of Mycobacterium leprae DNA from nasal swab among healthy children of East Java, Indonesia
"East Java has become one of the provinces that have higher prevalence of leprosy, especially in the coastal region. Environment has also influenced for leprosy transmission and early detection could reduce the incidence rate of new leprosy cases. Epidemiological studies of leprosy in children can give an illustration of the important aspects of the environment. Presence of Mycobacterium leprae (M. leprae) DNA in nasal swabs and seropositivity level among them can describe M. leprae exposure in that area. Results: From 301 students in Pacitan, 25 students (8.3%) are sero-positives and 9 students (2.9%) are PCR positives. from 229 students in Lamongan, 110 (48,3%) students are sero-positives and 49 students (21.4%) are PCR positives."
My comment this are just contacts. Infected with live and in the majority dead bacilli and their antigens. From other publications we know that only less then 10 % will develop disease. In most publications it is written that the positive contacts have subclinical disease. But I doubt whether just contact with antigens may call be subclinical disease. However, in many of the contacts even when they do not develop disease you find subclinical nerve damage. Is this leprosy? If so, do we have to reconsider the definitions of subclinical infection because in the contacts we find this damage.
In February I wrote in LML:
"In 1943 Fite stated that there was no leprosy without nerve damage. In 1977 Shetty and Antia published that nerves in early leprosy and in contacts showed signs of demyelination in nerve conduction studies and in histopathology. In 2017 Diogo Fernandes dos Santos presented during the Brazilian leprosy congress that during nerve conduction studies demyelination in contacts was seen, with and without a positive anti PGL-1 serology. Last year Glauber Voltan and Marco André Frade found enlarged nerves in contacts using ultrasound (personal communication). The enlargement was related to the amount of exposure. In these studies, no clinical symptoms due to nerve dysfunction were demonstrated. However, it is assumed that this damage only can be detected when more than 20% of the nerve fibres do not function properly.
Another observation goes back to just after the second world war. Stanley Browne in Belgian Congo observed that many leprosy contacts had hypopigmented patches with no obvious sensory loss which disappeared in most of the contacts, only a small percentage developed clinical leprosy. Pran Das and Caroline Le Poole suggested that this hypopigmentation in leprosy could be an autoimmune reaction to melanocytes or melanin synthesis as in vitiligo.
For all these observations one does not need live bacteria since contact with antigens is sufficient. It will, however, get worse if the contact is able to sustain M. leprae with the result that the bacilli will multiply. When these patients are treated and the treatment is discontinued, the environment in endemic circumstances will still afford contact with antigens and live bacilli. To make it even worse, after treatment of multibacillary patients there may be persisters who can start a relapse when the right circumstances are present.
It is clear from nature's experiment (HIV infection) that in more than 80 percent of the infected persons even severe depressed Cell Mediated Immunity does not give rise to a leprosy disease. There is obviously more to it than just a not well functioning adaptive immune system.
I ask you, has a nasal carrier a subclinical infection? Has someone with serological or Cell Mediated Immunity evidence of contact a subclinical infection?
Regards,
Ben
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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