Ref.: (LML) Super-spreaders and polar LL HD
From: Joel Almeida, London and Mumbai
Dear Pieter and colleagues,
You might be interested in these articles that highlight why super-spreaders require attention if we are to beat infectious diseases.
https://www.ijidonline.com/article/S1201-9712(11)00024-5/fulltext
https://www.nature.com/articles/d41586-021-00460-x
(CC.BY 4.0 licence)
Detailed studies have been done in viral diseases transmitted by droplet infection/aerosol, quantifying over-dispersion (where a large proportion of infected people infect no others, or only a few others, whereas a small minority infect many.) (1) This is quantified in the "k value". The smaller the k value, the smaller the proportion of infected persons who infect several others. The k value is fairly small in COVID, which is another way of saying that super-spreaders are responsible for a significant proportion of new cases.
The k value is several orders of magnitude smaller in HD (leprosy), possibly the smallest of any disease. How so? Polar LL (lepromatous) patients unprotected against HD bacilli can shed as many as tens of millions of viable bacilli per day. This is in marked contrast to even BL (borderline lepromatous) patients (2) It would take tens of millions of unprotected BL patients, to equal a single unprotected polar LL patient in terms of viable bacilli shed per day (unless the BL patients remain untreated and downgrade to LL HD). And probably billions of PB (paucibacillary) HD patients. The importance of LL HD in transmission is accentuated by the good natural immunity in most people. This means that heroic doses of concentrated viable bacilli are required to infect a typical human who is not in the grip of extreme poverty. Unprotected polar LL patients can provide astronomical numbers of concentrated viable bacilli, making them overwhelmingly important in transmission.
Polar LL patients also are exceptionally prone to excruciatingly painful ENL episodes if MDT is withdrawn after 12 months. If polar LL patients do not receive special attention, not only do they suffer but also transmission continues. Transmission has devastating consequences for too many people in endemic areas.
The incubation period of signs of reinfection is typically 6 years or more after withdrawal of anti-microbial protection, (3) and LLp patients are the most susceptible of all patients to (re)infection. Claims of low recurrence rates after 12 or 24 months of MDT in LL patients tend to be clouded by a few errors. The most common error is to include years zero to five after MDT in the denominator, and to mix LLp patients with others in the analysis. Also, to disregard changes in BI (bacillary index) at a single site, and to rely on inexpert (albeit trained) observers for diagnosis of recurrence. Such errors lead to underestimates of the critical risk, that of LLp patients being reinfected in endemic areas.
For those not from a biological or statistical background, such errors are akin to underestimating the incidence rate of dysmenorrhea by including pre-pubertal girls, or any males, in the denominator. Dysmenorrhea, of course, is not transmitted nor does it lead to irreversible damage. How much more important it is, then, to avoid errors when estimating the risk of reinfection among LLp patients in endemic areas.
Neglecting super-spreaders because they are a minority of patients would be an epidemiologically disastrous approach. To the HD bacilli, the human population and any susceptible hosts are nothing more than a culture plate. The priority is not to withhold anti-microbials from this culture plate, the human population, but to extinguish the infection before it blights more lives and before it develops resistance to affordable drugs.
Anti-microbial neglect of polar LL patients after 12 months of MDT is the central reason why 200,000 new cases have been detected every year (pre COVID), why huge areas remain entrapped in HD transmission, why LL patients suffer the excruciating pain of ENL, and why even otherwise well-run programmes fail to match the dramatic successes of Karigiri and Shandong. Those latter programmes relied on prolonged anti-microbial protection of LL patients, greatly reducing (re)infections and transmission. Their achievements hold important lessons.
As a community of science, compassion and justice, we aspire to end transmission and prevent ENL. To succeed, it is necessary to end the widespread anti-microbial neglect of polar LL patients who have completed 12 months of MDT. The evidence has been presented here at some length previously and can be rehearsed again at some length, in due course.
Fortunately, LML has hundreds of experts capable of reviewing claims and refuting errors fairly rapidly. Errors can survive a handful of reviewers, or even committees, as frequently happens. However, the half-life of errors tends to be shorter on LML than almost anywhere else, because it is an open platform enabling rapid open publication, with a membership that includes nearly all the world's most knowledgeable experts. Esteemed colleagues here typically are keen to assist others so that we all can keep improving our understanding of why some control programmes succeed but too many fail even if they are well-run.
We have the power to stop the infectiousness of genomically anergic super-spreaders (polar LL patients) in HD endemic areas, simply by adding sufficient anti-microbial protection against re-infection. We could champion quality care, not anti-microbial neglect. Prolonged anti-microbial protection of LL HD patients is a central pillar of quality care for them. It helps the patients avoid reinfection and evade the excruciating pain of ENL, as well as shutting down a major source of concentrated viable bacilli. It has transformed outcomes and impact in some formerly high endemic areas, and can do so in every endemic area.
Wouldn't it be good to match the achievements of highly successful programmes by interrupting transmission? We can facilitate this in endemic areas simply by preventing re-infection among any patients likely to have LL HD. Prompt diagnosis and prolonged anti-microbial protection of genomically anergic polar LL HD patients are probably the most important and indispensable actions we can take to interrupt transmission in endemic areas. Otherwise anti-microbial neglect before and after MDT reduces them to unwitting and unwilling super-spreaders.
Joel Almeida
References
1. Endo A, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Abbott S et al. Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China [version 3; peer review: 2 approved]. Wellcome Open Res 2020, 5:67 (https://doi.org/10.12688/wellcomeopenres.15842.3)
2. Davey TF, Rees RJ. The nasal dicharge in leprosy: clinical and bacteriological aspects. Lepr Rev. 1974 Jun;45(2):121-34.
3. Balagon MF, Cellona RV, dela Cruz E et al. Long-Term Relapse Risk of Multibacillary Leprosy after Completion of 2 Years of Multiple Drug Therapy (WHO-MDT) in Cebu, Philippines. American Journal of Tropical Medicine and Hygiene, 2009; 81, 5: 895-9. analysed in LML 2 June 2019
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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