Bacilliferous household contacts adversely influence leprosy reactions

Leprosy Mailing List – March 17th, 2011

Ref: Bacilliferous household contacts adversely influence leprosy reactions.

From: Barreto J A, Bauru, SP, Brazil

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Dear Dr Salvatore,

Thank you very much to Dr Ganapati for his comments (LML, March 13^th 2011).  He refers to my observation that patients with “intractable” recurrent erythema nodosum leprosum (ENL) reaction improve after treating their household contacts for lepromatous leprosy.  What could be the basis of this phenomenon?  He states that there should be a strong scientific reason to conclude that the bacilliferous household contacts will influence the reaction adversely and that the treatment of the contacts will help in any way.  Dr Ganapati asked if some light could be thrown on this hypothesis?

Herewith I am sending some references to support my opinion:
- Martins AC, Miranda A, Oliveira ML, Bührer-Sékula S, Martinez A. Nasal mucosa study of leprosy contacts with positive serology for the phenolic glycolipid 1antigen.Braz J Otorhinolaryngol. 2010;76(5):579-87.
- Job CK, Jayakumar J, Kearney M, Gillis TP. Transmission of leprosy: a study of skin and nasal secretions of household contacts of leprosy patients using PCR. Am J Trop Med Hyg. 2008;78(3):518-21.
- Hatta M, van Beers SM, Madjid B, Djumadi A, de Wit MY, Klatser PR. Distribution and persistence of Mycobacterium leprae nasal carriage among a population in which leprosy is endemic in Indonesia. Trans R Soc Trop Med Hyg. 1995;89(4):381-5.

These papers shine some lights on the likely causes of association between re-exposition and reactions. In the paper of Martins et al., there are many reports (from several authors) which suggest that the reaction (presentation of antigen leading to Th2 DTH and production of IgM antibodies) can start in nasal mucosa, even in not sick individuals.  This same paper shows that there was strong correlation between DNA of M. leprae in nasal mucosa and the levels of anti PGL-1 antibodies in serum.

In the others 2 papers it is suggested that nasal mucosa is the likely main important route of entry of bacilli.  We all know that type 1 or type 2 reactions begin after presentation of antigen, and that the outcome depends on the balance between genetic determined immunity of host and the bacilli load. Similarly to all other diseases caused by intracellular microorganisms.  After initial Th0 reaction, high amounts of antigens cause a shift towards Th2 reaction, while low levels lead to Th1.  This could explain several cases of BL patients developing ENL even before treatment or just after the start of anti-leprosy treatment.

Some (after 1year of treatment or later) present type 1 reaction, probably by the natural decreasing of antigens and consequent recovering of immune-cellular response, mimicking the IRIS phenomenon observed in AIDS.  By analogy with several other diseases, in which hypersensitivity (humoral or cellular) is observed after re-exposure to the same antigen, like rheumatic fever, acute glomerulonephritis, cutaneous tuberculosis, or even in other immunological diseases, like Wegener granulomatosis, Behçet's disease, Erythema Nodosum not related to leprosy, Sweet's syndrome (this latter shows histopathological features almost identical to ENL).  Where antigens of bacteria are implicated on the appearance of manifestations, it is nice to suggest that the same could occur with leprosy, isn't it?

Whether the triggering factors for reactions could be due to dormant bacilli multiplication, re-infection or re-exposure to M. leprae in a previous sensitized patient must be proved, but I think that none of these assumptions can be ruled out.  What I have commonly seen is:

1.cases of treated asymptomatic lepromatous leprosy patients developing ENL just after travelling to hyperendemic areas and;

2. improvement of patients with intractable reactions after diagnosis and treatment of their multibacillary (MB) household contacts.

Best regards,

Jaison A. Barreto
Instituto Lauro de Souza Lima
Bauru SP - Brazil