Leprosy Mailing List – October 7, 2020
Ref.: (LML) Realistic epidemiology, Twee Gebroeders, zero transmission/stigma/discrimination
From: Joel Almeida, London and Mumbai
Dear Pieter and colleagues,
Infectious diseases commonly lead to stigmatisation of those presumed infectious, and frequently their families too. Quarantines of those considered infectious often are required by law. Presumed infectious employees are asked to stay away from work, either temporarily or permanently. Screening of entire populations is undertaken to identify persons presumed infectious. Increasingly sensitive methods are used to unmask those infected persons who previously would have escaped detection. Household and neighbouring contacts of those presumed infectious increasingly are targeted for preventive treatment.
All this tends to be multiplied in the case of infections that cause visible disfigurement, such as HD (leprosy). People affected instantly can find themselves unemployable, unmarriageable, untouchable, neglected, segregated, imprisoned, even feared, hated, abused and persecuted. Therefore, it is not surprising that private practitioners, offering confidentiality, are an attractive option for persons who can recognise signs of HD in themselves.
However, does the realistic epidemiology of HD support stigma and discrimination? Important clues from the scientific literature include the following:
· Sufficiently prolonged courses of anti-microbials in even low-income populations have been known to lead to a 20%/year decline in MB HD rapidly leading to near-zero transmission, (1) whereas even Norway showed no greater than 10%/year decline (2)
· Treatment of PB HD patients does not diminish the risk of new HD among their household contacts, (3)
· Treatment of MB HD patients does not reduce the risk of new HD among their household contacts to the same low level as among the general population, (4)
· In affluent countries HD behaves largely as a non-infectious disease, (5)
· HD bacilli isolated from sphagnum moss in Norway almost never produce clinical disease, (6)
· Monozygotic twins with disseminated types of HD were reported to show a 70% concordance of HD type while dizygotic twins showed only a 20% concordance (7)
· Multiple-case "de novo" LL families are known, (8) even though the average incidence rate of "de novo" LL HD in the population remains under 1 in 100,000/population/yr
· Concentrations of environmental HD bacilli never approach that found in the nasal excretions of infected persons with LLp genomes, (9)
· Strong geographical clustering is observed among newly diagnosed HD patients (10)
· The type of the index patient trumps socio-economic variables in predicting HD among contacts, (11)
· etc.
Unless our epidemiology can explain ALL such clues, we are likely to adopt unrealistic assumptions. Mathematical models based on unrealistic epidemiology and biology tend to yield unrealistic predictions and encourage sometimes counter-productive interventions.
A reasonably careful review of clues suggests the following understanding about the epidemiology of HD.
Fig. 1. Only untreated LLp or LL patients have been known to shed astronomical numbers of viable bacilli per day. Most HD patients are non-infectious even without treatment. Nearly ALL patients with well-defined skin patches are non-infectious even without treatment.
Fig. 2. Unprotected persons with LLp genomes are the near-exclusive source of astronomical numbers of highly concentrated viable HD bacilli. Persons with other genomes rarely might shed comparable numbers of viable bacilli in high concentration, but only if they deteriorate to develop LL HD. Armadillos are the only other known natural source of highly concentrated viable bacilli in such astronomical numbers. Persons newly developing signs of HD might wrongly blame any household members or neighbours or co-workers with skin patches. However, the true source of most viable bacilli is usually a previously treated but now unprotected re-infected person with an LLp genome, or a never-diagnosed person with an LLp genome and few or no physical signs of HD. The only proven way so far rapidly to achieve zero transmission is to ensure prolonged anti-microbial protection for ever-diagnosed LLp HD patients. Without that, stagnation in HD control is highly likely regardless of all other interventions.
Fig. 3. Only a minuscule fraction of human populations (to the right of the red line in the schematic diagram above) have the LLp genomes which permit them to be infected rapidly by a relatively modest dose of viable bacilli. Nearly all of the world's remaining population is either completely immune, or has very high ID50s and develops forms of HD that are either completely non-infectious or only trivially infectious. HD clings precariously to human populations. It has been known to die out, slowly but steadily, in many contexts and continents across the ages. Anti-microbials successfully have curtailed many of the worst disfigurements of HD, but unhelpful use of anti-microbials paradoxically has been keeping HD transmission alive and can do so indefinitely (for reasons that deserve full discussion at another time).
The only proven way so far to achieve zero transmission rapidly is to ensure prolonged anti-microbial protection for persons with LLp genomes. The reproductive number R0 of LL HD is the critical parameter in interrupting transmission. We usefully could focus on the R0 of LL HD if we want to emulate and match rapid success.
It is demonstrably more effective to control sources of astronomical numbers of viable bacilli than to let them continue and then try to mop up the consequences among contacts
In 1953 the Netherlands experienced a major flood that covered a significant expanse of land and killed almost 2000 people. Holland already was noted for defensive dykes that kept the sea out of low-lying land. These proved insufficient to keep out storm waters on one particularly stormy night. The waves had started to erode a high sea dyke making a breach almost inevitable. Such a breach would have resulted in swift and complete flooding of a densely populated area. Mayor Vogelaar of Nieuwerkerk requisitioned Arie Evegroen's grain barge Twee Gebroeders to reinforce the weakened dyke. The barge was steered into the breach, and saved the flood defences. This true story is now legendary.
There is no substitute for a solid sea defence, and there is no substitute for the prolonged anti-microbial protection of LL HD patients (ever-diagnosed). The alternative in Holland would have been to blame the floods on gardeners who use watering cans, and to offer hand towels to people around them. That would not have stopped the flood or kept people dry, any more than post-exposure prophylaxis among contacts can stop HD while previously treated LL HD patients are neglected. Further, the hapless gardeners would have been stigmatised wrongly for causing the great flood with their watering cans, just as non-infectious HD patients are presumed wrongly to be infecting their contacts. Esteemed Dutch (and other) colleagues might remember the great flood of 1953 and apply it to the epidemiology of HD. Prolonged anti-microbial protection of ever-diagnosed LL HD patients is equivalent to the Twee Gebroeders barge, and perhaps even to a high sea dyke. It is necessary in order to stop the flood of highly concentrated viable bacilli, in astronomical numbers, from LL HD patients. It is also necessary to protect the patients themselves from the ravages of the bacilli.
Mistaken epidemiology increases transmission through neglect of previously treated LLp HD patients, and increases stigma and discrimination through misinterpretation of surveillance by contacts of non-infectious patients (who mostly have well defined skin patches). There is no epidemiological (or other) reason for stigmatising non-infectious patients, who form the vast majority of patients diagnosed by active case-finding. Further, all known LLp HD patients can be maintained in a non-infectious state, alongside due attention to their general medical/surgical and psycho-socio-economic care. Ending the neglect of previously treated persons with LLp genomes would comply with the Universal Declaration of Human Rights article 25.1. Importantly, it is the surest proven way rapidly to achieve near-zero transmission and near-zero stigma/discrimination.
Wouldn't it be good to succeed rapidly with zero transmission? And to do it in a way consistent with zero stigma/discrimination and due respect for human rights? We know how to do it, thanks to demonstrable successes. Let's help make it happen, or at least allow sufficient elbow room for the people and professionals of endemic countries to succeed.
Joel Almeida
References
1. Li HY, Weng XM, Li T et al. Long-Term Effect of Leprosy Control in Two Prefectures of China, 1955-1993. Int J Lepr Other Mycobact Dis. 1995 Jun;63(2):213-221. reviewed & analysed further in: 11 a. Almeida J. What really happened in Shandong? LML 16 Nov 2019
2. Irgens LM. Leprosy in Norway. An epidemiological study based on a national patient registry. Lepr Rev, Volume 51, Supplement 1, March 1980
3. Butlin CR, Nicholls P, Bowers B et al. Outcome of late healthy household contact examinations in leprosy-affected households in Bangladesh. Lepr Rev (2019) 90, 305 – 320
4. Vijayakumaran P et al. Does MDT Arrest Transmission of Leprosy to Household Contacts? Int. J. Lepr. (1998) 66(2): 125-130.
5. Suárez-García I, Gómez-Barroso D, Fine PEM. Autochthonous leprosy in Spain: Has the transmission of Mycobacterium leprae stopped? PLOS NTD September 16, 2020
6. Kazda J, Irgens LM, Kolk AHJ. Acid-fast bacilli found in sphagnum vegetation of coastal Norway containing Mycobacterium leprae-specific Phenolic glycolipid-I. Int. J. Lepr. 1990;58(2):353-7
7. Chakravarti MR, Vogel F. A twin study on leprosy Georg Thieme Publishers, Stuttgart, Germany; 1973
8. Central Leprosy Division, India. Epidemiological investigation of multiple cases occurring in one family in village Salaunikhurd. NLEP newsletter Vol III, Issue 3, July – Sept 2018
9. Davey TF, Rees RJ. The nasal dicharge in leprosy: clinical and bacteriological aspects. Lepr Rev. 1974 Jun;45(2):121-34.
10. Fontes ANB, Lima LNGC, Mota RMS et al. Genotyping of Mycobacterium leprae for better understanding of leprosy transmission in Fortaleza, Northeastern Brazil. PLoS NTD. 2017 Dec; 11(12): e0006117.
11. Teixeira CSS, Pescarini JM, Alves FJO. Incidence of and Factors Associated With Leprosy Among Household Contacts of Patients With Leprosy in Brazil. JAMA Dermatol. 2020;156(6):640-648. doi:10.1001/jamadermatol.2020.0653
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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