Monday, August 31, 2020

Fw: (LML) Transmission of HD (leprosy) is maintained by covert recurrence

 

 


Leprosy Mailing List – August 31,  2020

 

Ref.: (LML) Transmission of HD (leprosy) is maintained by covert recurrence

 

From:  Pieter Schreuder, Maastricht, the Netherlands

 

Dear colleagues,

 

Something went wrong with the mail of last Fryday, August 28, "Transmission of HD (leprosy) is maintained by covert recurrence" by Joel Almeida.

 

Figure 2. "Newly reported MB patients by year, Shandong (China).  Rapid decline at a time of low income. Decline sustained until eventual near-zero transmission."did not show in the attached file.

 

By this letter the missing file.

 

Best regards,

 

Pieter AM Schreuder

Editor LML


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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Friday, August 28, 2020

Fw: (LML) Transmission of HD (leprosy) is maintained by covert recurrence




Leprosy Mailing List – August 28,  2020

 

Ref.:  (LML) Transmission of HD (leprosy) is maintained by covert recurrence

 

From:  Joel Almeida, London and Mumbai

 

 

Dear Pieter & colleagues,

 

Recent LML contributions (eg., Pai, LML 27 July 2020) have drawn attention to the risk of recurrent HD among patients with LL HD. Evidence from Brazil (Sartori PVU, Penna GO, Bührer-Sékula S et al 2020) lends support to the view that genetic risk factors predispose to re-infection/relapse/recurrence. The evidence below underlines the importance of recurrent HD. Implications for action are discussed.

 

Learning from past successes, and even past failures, can help us more rapidly and surely to end transmission while limiting disability, extreme poverty and exclusion.

 

Joel Almeida

 

= = = = = = = = = = = =

 

Transmission of HD (leprosy) is maintained by covert recurrence among previously treated LLp (polar lepromatous) patients

 

Abstract

 

Long-term follow-up of a cohort after 24 months of MDT (multi-drug therapy) reveals that among LLp HD (polar lepromatous leprosy) patients in an endemic area, recurrence rates are higher than previously believed: >5/100 person-years at risk from year 6 onwards following the end of MDT. Recurrent bacillary multiplication may be due to exogenous re-infection, endogenous relapse or both. Evidence suggests that genetic risk factors predispose individuals to recurrence of HD.

 

By contrast, during the first 5 years after the end of MDT, clinically diagnosed recurrence rates are low (less than 0.5/100 person-years at risk). However, this may be partly because it is not easy promptly to detect multiplication of bacilli. The risk of recurrence is predicted to be higher in hyper-endemic areas than elsewhere.

 

Transmission demonstrably and rapidly can be reduced by deliberate efforts using anti-microbial chemotherapy. This was demonstrated in both Shandong (China) and Uele (DR Congo). A 17% to 20%/year decrease in newly detected MB (multibacillary) HD patients was demonstrated there at a time when those places still had relatively low income. Prolonged anti-microbial protection for persons with LLp genomes was the critical ingredient in both places. In Uele at that time, income not only had been low for some time but also was declining. Low and declining income did not suffice to maintain transmission rates in the face of prolonged anti-microbial protection for LLp HD patients. In Shandong, prolonged anti-microbial protection for LLp HD patients (among others) was maintained until near-zero transmission. This approach, although contrary to global fashions, led to a decline of about 20%/year in newly detected MB patients. This relatively rapid decline was sustained until near-zero transmission.

 

At global level, in contrast to the success described above, the number of newly detected MB patients per year has stagnated compared to the 1980s. HD is known to be an important cause of extreme poverty and social exclusion, in addition to being a putative consequence of poverty. Ending HD and caring for those previously treated therefore makes a useful contribution to ending extreme poverty and breaking the downward spiral of disease leading to poverty leading to still more disease.

 

Persons with LLp genomes and unrecognised/untreated recurrence uniquely are capable of shedding astronomical numbers of highly concentrated viable bacilli. This can maintain transmission despite all other efforts to control HD. Further, active LLp HD is far more prevalent among previously treated MB patients than among the general population, by a factor of about 10,000 (ten thousand times more prevalent). Among previously treated MB patients known to have LLp HD, the excess risk of active LLp HD is likely to be even more frequent still, by several orders of magnitude. 

 

Active case-finding therefore should give top priority to detecting active LLp HD among previously treated MB patients, so as to give them the highest level of protection against destitution, exclusion, further disability, and bacilli. Previously treated patients now experiencing destitution should receive the greatest priority for such protection. 

 

The Sasakawa Health Foundation contributed financially to the rapid success in Shandong, allowing local professionals the elbow room to depart from global fashions in order to improve outcomes. Such respectful partnership between financing organisations and local professionals offers excellent prospects for ending the transmission of HD, because it enables rather than disables scientifically astute local talent that is constantly assimilating subtle front-line clues. 

 

Based on past successes, ending the anti-microbial neglect of previously treated LLp patients is likely to close the critical gap through which HD continues to be transmitted. It would be good to join and assist the people and professionals of endemic countries in closing this critical gap (or at least allow them sufficient elbow room to succeed).  By ending the too-frequent neglect of previously treated LLp HD patients, we are likely to hasten the end of HD transmission.

 

Voices of people afflicted by HD are important catalysts for bringing about the required changes. Words about the desirability of ending all world poverty are not an adequate substitute for actions that remedy the drop in income that too often accompanies disfiguring sequelae of HD.

 

 

 

Recurrence rate after MDT

 

The recurrence rate of clinical HD (leprosy) in years 6 to 20 following the end of MDT (multi-drug therapy) was demonstrably in the region of 5/100 person-years at risk or more, among persons with an initial BI (bacterial index in slit skin smears) of 4+ or greater. (1, 1a) MDT in that study included 24 monthly doses of rifampicin. 5/100 PYAR (person-years at risk) is more than a negligible rate of recurrence.

 

By contrast, during years 0 to 5 following the end of 24-month MDT in that same study, the corresponding risk was less than 0.5/100 PYAR (person-years at risk). Therefore, an insufficient duration of observation can underestimate, by a relatively large margin, the eventual cumulative recurrence rate in this group of patients.

 

The observed recurrence rate in excess of 5/100 PYAR, 6 or more years after the end of MDT, equates to eventual recurrence among 75% to 100% of persons with an initial BI of 4+. That assumes survival of such a treated person for 25 years or more after the end of MDT. Such survival is commonplace. 75% to 100% eventually showing recurrent HD is more than a negligible proportion of such patients.

 

Further, persons with LLp genomes uniquely are capable of shedding astronomical numbers of viable bacilli when left unprotected against bacilli. (2) Such unprotected persons also bear the full weight of (covert or overt) bacillary multiplication and its complications. Therefore, there is good reason for giving top priority to such persons who have ever shown high bacillary loads, and their contacts.

 

A previously treated LLp patient with recurrence of HD will usually take some time to show obvious clinical signs or marked increases in BI. Bacilli easily can multiply and spread to others before recurrence is recognised. Ensuring sufficient care for such patients following MDT not only would respect their human rights and help slow the deterioration of their disabilities, but also would close the critical gap in our efforts to end transmission.

 

The most powerful evidence supporting such action comes from highly successful programmes. A 20%/year decline in new MB patients/year, leading to near-zero transmission, was achieved (in Shandong, with the support of the Sasakawa Health Foundation). (3, 3a, 4) Therefore, such major and lasting success can be achieved again. Even Uele (DRCongo) achieved a 17%/year or greater decline in new MB patients/yr at a time of low and declining GDP per capita. (5, 5a) Prolonged anti-microbial protection for persons with LLp genomes was the critical ingredient in both Shandong and Uele, reducing transmission relatively rapidly.

 

Implications for action

 

In order to end transmission, and protect affected individuals, it seems necessary to include prolonged anti-microbial protection after MDT for persons who have ever shown a high BI.

 

 

 

Underestimates of recurrence risk

 

The risk of recurrence can be underestimated if the denominator of such estimates includes persons unlikely to have LLp (polar lepromatous) genomes. That would be like estimating the risk of ovarian cancer by studying a population of professional footballers, ignoring the fact that most professional footballers are male. Or estimating the risk of ovarian cancer by studying girls under 10 years of age, in whom the risk is very low. Similarly, most persons with even MB (multibacillary) HD starting MDT do not have LLp genomes. Therefore, their risk of recurrent HD following MDT is relatively low. Such underestimates do not justify complacency about the risk.  

 

One study (6) compared 6 months of MDT with 12 months of MDT (historical controls). That study happened to include only three patients with a BI of 6+ at all sites. (Aung & Butlin, personal communication) All three patients happened to be in the 12-month MDT group. These three patients are likely to have had a relatively boosted risk of recurrence, owing to their genomes apparently permitting unrestrained proliferation of bacilli. The 6-month MDT group happened to have no such patients. This under-representation in the 6-month group was unintended and unplanned, but still relevant to the analysis. Accordingly, recurrence rates in the 6-month group are expected to be underestimated relative to the 12-month group. 

 

Further, the 12-month MDT group was reported to have an average duration of 8.3 years of observation, including the 12 months of MDT. This is the same as 7.3 years of observation following the end of MDT. It amounts to an average of only 2.3 years of observation beyond the low-risk initial 5 years. During those 2.3 years the three patients with a BI of 6+ at all sites contributed roughly 7 PYAR. No recurrence of HD was detected among them. Therefore the apparent recurrence rate among these three BI 6+ patients from the sixth year of observation onwards was less than 1 in 7 PYAR . That equates to a risk of less than 14/100 PYAR in years 6 and beyond (upper 95% confidence limit <40/100 PYAR). <14/100 PYAR and <40/100 PYAR are far from trivial recurrence rates, among persons who permitted unrestrained proliferation of bacilli. On the other hand, as mentioned above, the 6-month group included not even a single patient with BI 6+ at all sites. Therefore, not a single PYAR among such patients was available from the 6-month MDT group. Given zero PYAR, the only safe conclusion is that the risk of recurrence among such patients, had any occurred in the 6-month MDT group, would have been less than 100/100 PYAR. 100% recurrence rate, the 95% upper confidence limit in this case, is more than a negligible proportion.

 

Implications for action

 

Ensure an adequate duration of MDT, not less than 12 months, in persons with a high initial BI at all sites.

 

Give prolonged anti-microbial protection after MDT, to persons with a high initial BI at all sites.

 

 

 

Detecting bacillary multiplication after MDT

 

Recurrence after treatment can be defined as multiplication of bacilli. WHO (the World Health Organization) uses this definition for relapse in HD. Further, recurrence may be caused by endogenous relapse or exogenous reinfection, (7, 8) or even both simultaneously. There is some evidence supporting the prediction that the human genome influences susceptibility to MB HD (9) and recurrence of HD. (10)

 

The occurrence and extent of bacillary multiplication can be estimated by quantitative PCR performed on serial dilutions of successive samples of bacilli compared to reference controls. Confirmation of viability can be obtained by inoculation into footpads of immunologically compromised mice. Alternatively, the samples might permit viability PCR, a technique that has apparently yet to be tried or ruled out for these bacilli.  

 

Less sensitive approaches have often been used (understandably so, under routine programme conditions) in assessing multiplication of bacilli among previously treated patients. These include an increase in BI of 2+ (100-fold) at any one site, or the appearance of new lesions. An even less sensitive criterion of bacillary multiplication is an increase in average BI (average of four to six sites) rather than an increase at just one site. This latter criterion is conspicuously insensitive because even a spectacular increase from 0+ to 6+ BI at one skin smear site would fail to increase the average BI by more than about 1.5+. That means many, if not most, instances of early recurrence could be missed by this insensitive criterion. This "low sensitivity" criterion was used in at least one study. (6) "Low sensitivity" approaches can overlook even considerable multiplication of viable bacilli. This allows serious underestimates of the true cumulative recurrence rate, especially if the duration of observation is measured in years (6) rather than decades.(1)

 

Implications for action

 

Research: At least one cohort of patients who have high initial BI at all sites should be followed up using highly sensitive methods of detecting bacillary multiplication starting with the end of MDT and continuing for a duration well beyond 10 years.

 

Treatment: Give prolonged anti-microbial protection after MDT, to persons with a high initial BI at all sites.

 

 

The frequency of LLp patients among previously treated patients vs the general population

 

Roughly 16 million persons have ever been treated with MDT, including over 10 million persons in India. About 1% of them are likely to have genomes that readily permit unrestrained proliferation of bacilli. This is estimated from a field programme of the Schieffelin Centre in Karigiri, India, where meticulous contact tracing was done over decades (11). This would equate roughly to about 100,000 out of 10 million previously treated persons in India with genomes permitting unrestrained bacillary proliferation. They are therefore highly susceptible to re-infection after MDT. These persons are actual or potential sources of astronomical numbers of viable bacilli, as noted above.  

 

Further, each year about 125,000 persons with signs of clinical HD are newly detected in India, including about 1,250 persons likely to have LLp genomes. If we merely treat the 1,250 newly detected while neglecting the 100,000 previously treated but probably with LLp genomes, our epidemiological impact is predicted to be disappointing. Such disappointing impact has been observed.

 

The figures above have implications for case-finding, as discussed now.

 

The incidence rate of new highly bacillated patients among the general population is in the region of (1,250/1.3 billion =) 1 per 100 million population/year.

 

The incidence rate of highly bacillated recurrent HD among previously treated MB patients is about (5/100 x 0.2% =) 1 per 10,000 previously treated MB patients/year.

 

Therefore, to discover one person with probable active LLp HD, it is necessary to examine about 100 million of the general population. Whereas it is sufficient to examine about 10,000 previously treated MB patients. Therefore, it seems important to give priority to previously treated MB patients when looking for persons with active LLp HD.

 

Examination of previously treated MB patients experiencing destitution in two towns of India revealed that 17% of them had positive skin smears. (12) Among those experiencing HD-related destitution, therefore, 1,700 out of 10,000 previously treated MB patients could well have recurrence of HD. They are highly important persons deserving the greatest level of ongoing protection against destitution, exclusion, further disability, and bacilli. Neglecting them would be a serious error of public health, involving also a disregard for their human rights.

 

Just as it is more important to examine previously treated MB patients than to examine the general population for active LLp HD, so it is more important to actually eradicate extreme poverty among destitute previously treated MB patients than to talk about the desirability of a global end to all poverty.

 

Implications for action

 

Active case-finding should give top priority to detecting active LLp HD among previously treated MB patients, so as to give them the highest level of protection against destitution, exclusion, further disability, and bacilli. Previously treated patients now experiencing destitution should receive the greatest priority for such protection.

 

Research: In a sample of previously treated MB patients, highly sensitive molecular techniques can be used to detect even covert bacillary multiplication in serial samples subjected to quantitative serial dilution techniques.

 

 

The consequences of neglecting previously treated LLp patients

 

The number of new MB patients/year has shown little or no decline in recent decades despite our best efforts.

 

 Figure 1. Newly reported MB patients by year, globally.  Relative stagnation.

 See attached file

 Figure 2. Newly reported MB patients by year, Shandong (China).  Rapid decline at a time of low income. Decline sustained until eventual near-zero transmission.

 See attached file

The number of new PB patients/year is highly sensitive to the frequency of case-finding campaigns (13, 13a), but the number of new MB patients/year less so. Similarly, financial incentives to field workers tend artificially to depress the reported proportion of newly detected patients showing grade 2 disability, but the number of new MB patients/year is less sensitive to distortion by such financial incentives. Persons with MB signs rarely self-heal. Sooner or later, they come to the attention of health services. Therefore, the number of newly detected MB patients/year is more useful than the total of all newly detected patients/year.

 

The number of new bacillated patients per year often has failed to decline at 20%/year in hyper-endemic areas where prolonged anti-microbial chemotherapy for LLp patients was omitted or, prior to the sulfones, unavailable. Even dramatic improvement in socio-economic conditions has so far not proved sufficient to achieve a 20%/year decline in newly detected MB patients in hyper-endemic areas. In Norway, where near-zero transmission was reached before the introduction of effective anti-microbial chemotherapy, (14) the rate of decline of newly reported bacillated patients/year remained well below the 17%/year or greater achieved in Uele, DRCongo. Uele, notably, had low and declining income.

 

Interestingly, the frequency of new MB patients/year is often observed to be higher around places to which previously treated LLp patients gravitate (including many institutions that have diligently served HD patients for many decades). Instead of the good work there leading to a marked local decline in transmission, it appears to have led to a local increase in transmission relative to other places. That is probably partly because LLp HD patients gravitating there generally have been denied prolonged anti-microbial protection. This not only exposes the individuals unnecessarily to harm, but also allows HD to keep spreading.

 

Implications for action

 

Give prolonged anti-microbial protection after MDT, to persons who have shown a high BI ever.

 

 

Transforming our outcomes and impact

 

Neglect of previously treated persons with LLp genomes not only seems disrespectful of their human rights, and damaging to those individuals, but also has serious consequences for the population. That is because it allows the spread of viable bacilli to children and others.

 

Prolonged anti-microbial protection of persons with LLp genomes is necessary for rapid decline in new MB patients/population/year. This requires prophylactic anti-microbial protection after MDT in the high-risk group of patients likely to have LLp genomes. Monthly doses of 3 bactericidal drugs are likely to work well for this purpose. (15, 16)

 

Implications for action

 

In endemic areas, patients who have shown a high BI (ever) should be given a full course of MDT followed by monthly doses of 3 bactericidal drugs to protect them against re-infection (eg., Rifampicin + Minocycline + Moxifloxacin or with Clarithromycin in place of Moxifloxacin)

 

 

 

Discussion

 

Prolonged anti-microbial protection for those with LLp genomes is a demonstrably effective way of shutting down a major source of transmission in HD while upholding the right of HD-affected persons to necessary and competent health care.

 

Analogies can aid understanding. When dealing with a flooded bathroom, it is not sufficient to focus on mopping up the water while neglecting to turn off the tap. Similarly, merely trying to protect those exposed is not as effective as interrupting transmission at source. That demonstrably can be achieved by prolonged anti-microbial protection for previously treated LLp HD patients.

 

Previously treated patients with LLp genomes typically have been neglected in recent decades. Using another analogy, refusing them prolonged anti-microbial protection and comprehensive care, merely because they were previously treated, is like firemen refusing to attend a wooden storage shed for inflammable fuels merely because a fire was extinguished there previously. It seems more humane to provide previously treated LLp patients with the anti-microbial protection they require. Anti-microbial neglect of previously treated LLp HD patients emerges also as one of the most important reasons maintaining transmission of HD. It seems not entirely consistent with ethics, human rights and science.

 

The Sasakawa Health Foundation contributed financially to the success in Shandong (China), without requiring local professionals to follow global fashions that turned out to be ineffective. This model of respectful partnership between financing organisations and local experts offers excellent prospects for ending the transmission of HD and reducing its sequelae. That is because it enables rather than disables scientifically astute local talent that is constantly assimilating subtle front-line clues. 

 

Even low-income areas (Uele, DR Congo) rapidly have reduced transmission by using MDT backed up by prolonged anti-microbial protection for persons with LLp genomes. Ending transmission also helps shut down a significant cause of extreme poverty. Such measurable impact against extreme poverty seems worthwhile. It also seems more realistic and effective than mere words decrying global poverty.

 

In the landmark public interest litigation by the great lawyer Pankaj Sinha on behalf of neglected HD-afflicted persons against the Govt. of India, the advocate Colin Gonsalves described to the Supreme Court the predicament of many previously treated HD-afflicted persons: "they are driven to streets and eventually turn to begging" "compelled to live in so-called leprosy homes where they are treated as unpersons or aliens". It is remarkable that Mr. Sinha is physically blind. He apparently can see more clearly than many of us who are not physically blind.

 

Full respect for human rights and open scientific discussion would seem not only highly conducive to ending transmission, but also in keeping with our best selves. We are all explorers and learners, we all make mistakes but correct them eventually. When our eyes, ears and minds are kept open, the wealth of clues from the front-lines can lead us increasingly towards the truth. The truth alone can set people free from the ravages of HD.

 

 

Conclusion

 

We can match past successes in reducing transmission relatively rapidly even in places with as low a per capita income as Uele (DR Congo). A 20%/year decline in newly detected MB patients, leading to near-zero transmission, has been demonstrated by ensuring prolonged anti-microbial protection for highly bacillated MB patients. Such a rapid decline therefore is achievable. The people of endemic countries deserve no less. The noble values we profess permit no less. Let's do it.

 

 

References

 

1. 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. reviewed & analysed further in:

1a. Almeida J, Recurrence rate among MB patients following RFT. LML 2 June 2019

 

2. Davey TF, Rees RJ. The nasal dicharge in leprosy: clinical and bacteriological aspects. Lepr Rev. 1974 Jun;45(2):121-34.

 

3. 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:

3a. Almeida J. What really happened in Shandong? LML 16 Nov 2019

 

4. Shumin Chen, Yunchun Zheng, Min Zheng, Demin Wang. Rapid survey on case detection of leprosy in a low endemic situation, Zhucheng County, Shandong Province, The People's Republic of China. Lepr Rev (2007) 78, 65–69.

 

5.  Tonglet R, Pattyn SR, Nsansi BN et al. The reduction of the leprosy endemicity in northeastern Zaire 1975/1989 J.Eur J Epidemiol. 1990 Dec;6(4):404-6

reviewed in:

5a. Almeida J. Reducing transmission in poor hyperendemic areas - evidence from Uele (DRC). LML 29 Nov 2019

 

6. Butlin CR, Aung KJM, Withington S et al. Levels of disability and relapse in Bangladeshi MB leprosy cases, 10 years after treatment with 6m MB-MDT. Lepr Rev (2019) 90, 388–398.

 

7. Almeida JG, Jesudasan K, Christian M, Chacko CJG. Relapse rates in lepromatous leprosy according to treatment regularity. Int J Lepr 1986 Mar;54(1):16-20.

 

8. Stefani MMA, Avanzi C, Bührer-Sékula S et al. Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases. PLoS Negl Trop Dis (2017) 11(6): e0005598.

 

9. Chakravarti MR, Vogel F. A twin study on leprosy Georg Thieme Publishers, Stuttgart, Germany; 1973

 

10. Sartori PVU, Penna GO, Bührer-Sékula S et al. Human Genetic Susceptibility of Leprosy Recurrence. Scientific Reports (2020) volume 10, Article number: 1284

11. Norman G, Raja Samuel Bhushanam JD, Samuel P. Trends in leprosy over fifty years in Gudiyatham Taluk, Vellore, Tamil Nadu. Indian J Lepr. 2006 Apr-Jun;78(2):167-85.


 12. Rao PS, Mozhi NM, Thomas MV. Leprosy affected beggars as a hidden source for transmission of leprosy. Indian J Med Res. 2000 Aug;112:52-5.

13. Xiang-Sheng Chen, Wen-Zhong Li, Cheng Jiang, & Gan-Yun Ye. Leprosy in China: epidemiological trends between 1949 and 1998. Bull. WHO, 2001, 79: 306–312
reviewed & analysed further in:
13 a. Almeida J, Classification of patients and interruption of transmission. LML 14 Apr 2019

14. Irgens LM. Leprosy in Norway. An epidemiological study based on a national patient registry. Lepr Rev, Volume 51, Supplement 1, March 1980

15. Almeida J. Example protocol for safely interrupting transmission of Hansen's Disease. LML 4 Nov 2019 

16. Pardillo EF, Burgos J, Fajardo TT et al. Powerful Bactericidal Activity of Moxifloxacin in Human Leprosy Antimicrob Agents Chemother. 2008 Sep; 52(9): 3113–3117. doi: 10.1128/AAC.01162-07

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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Saturday, August 22, 2020

Fw: (LML) Dioraphte 2020 - 2021 call all for research proposals on skin-relatedNeglected Tropical Diseases (NTDs).

 


Leprosy Mailing List – August 22,  2020

 

Ref.:  (LML) Dioraphte 2020 - 2021 call all for research proposals on skin-relatedNeglected Tropical Diseases (NTDs).

 

From:  Bouke de Jong, Antwerpen, Belgium

 

 

Dear Dr. Schreuder and colleagues,

 

Dioraphite, a private charitable Foundation established in the Netherlands, has established a fully funded research programme for Neglected Tropical Diseases (NTDs) with a specific focus on Skin NTDs (www.dioraphte.nl). 


This is a call for research proposals on skin-related Neglected Tropical Diseases (NTDs). CfP-NTD2021DIORAPHTE. The Dioraphte Foundation has decided to continue its support for translational and clinical experimental research that underpins the understanding of pathophysiology and pathogenesis of Skin-related NTDs.


The scope includes clinically driven basic research questions that precede clinical trials for improved drugs, treatments, diagnostics or vaccines. Transdisciplinary approaches to research studies designed to be embedded in endemic clinical settings are encouraged.


In this 2nd call for research proposals on the Foundation will give priority to five areas:

-        (i) Immunology, pathophysiology, pathogenesis, or metabolic processes during infection that could lead to improved drugs, treatments, diagnostics or vaccines.

-       (ii) Improved experimental or population models of skin infection to support research into improved drugs, treatments, diagnostics or vaccines.

-       (iii) Innovative approaches to the discovery and development of drugs, diagnostics or vaccines.

-       (iv) Underlying pathology in diverse endemic populations that determines variation in response to diagnostics, drugs or vaccines.

-       (v) Role of skin commensals and co-infections in disease.

 

Proposals linking groups that have expertise in NTDs to those with expertise in skin research, in academic, public or private sectors, are encouraged.

In this 2nd call for 20211.7 million euros will be available to fund 2-4 proposals. Proposals should be for 2 to 4 years with a maximum budget of 850,000 Euros.

 

Bouke de Jong

Unit of Mycobacteriology

Institute of Tropical Medicine

Antwerpen, Belgium


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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Friday, August 21, 2020

Fw: (LML) Summer 2020 Edition of the WHO Goodwill Ambassador's Newsletter


 

 


Leprosy Mailing List �C August 21,  2020

 

Ref.:  (LML) Summer 2020 Edition of the WHO Goodwill Ambassador's Newsletter

 

From:  Takahiro Nanri, Tokyo, Japan

 

Dear Dr Schreuder and Friends,   

 

Warm greetings from Sasakawa Health Foundation in Tokyo. We have pleasure in announcing the publication of the Summer 2020 Edition of the WHO Goodwill Ambassador's Newsletter https://www.shf.or.jp/wsmhfp/wp-content/uploads/2020/05/11th-202005newsletter100-web.pdf?lang=en

 

This issue is being published as a digital magazine and as a PDF, with a print version to be mailed to subscribers in due course. It is the last edition in the current format before the newsletter transitions to a new look in the coming months.   

 

In this issue, we feature:

 

Ambassador's Message 
You Have My Support
In 2019, I made 27 trips abroad in various capacities. 

Report
Helping People to Help Themselves
COVID-19 response projects aim to assist and empower persons affected by leprosy. 

 

Interview
Going Forward Together
Sasakawa-India Leprosy Foundation's new CEO is a strong believer in partnerships. 

 

Viewpoint
Lessons from Brazil
Thoughts on "elimination" in leprosy and some of its ironic consequences. 

Book
A Story Both Tragic and Uplifting
A family secret inspires a book on leprosy, stigma and the fight for justice. 

News  
Special Rapporteur's Term Extended
Persons affected by leprosy will continue to have a voice at Human Rights Council. 

News  
Info Hansen Debuts

A hub for information about Hansen's disease launches from Brazil. 

 

We hope you enjoy our latest issue and welcome your comments and contributions to the newsletter. 

 

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email: shf_55@shf.or.jp

visit our website at https://www.shf.or.jp

 

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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Thursday, August 20, 2020

Fw: (LML) Lack of MDT in Brazil


 

 

Leprosy Mailing List – August 20,  2020

 

Ref.:  (LML) Lack of MDT in Brazil

 

From:  Joel Almeida, London and Mumbai


 

Dear Pieter and colleagues,

 

Thanks to Prof. Claudio Salgado for drawing attention to this critical matter (LML, August 18, 2020). Brazilian colleagues are great and include many of the world's top experts. Not just in HD (Hansen's disease) but also in supply chain management. Everyone wishes Brazil well, and with the combined efforts of all the relevant experts and authorities, the issues will no doubt be resolved urgently.

 

As Novartis' noble donation and maintenance of MDT production continue, aided no doubt by the personal commitment of the great Vas Narasimhan (CEO), the rest of the supply chain will surely catch up. Then no patient will lack MDT. 

 

Otherwise trying to fight HD without MDT is like trying to put out a fire with a hosepipe that lacks water.

 

Best wishes to our esteemed Brazilian colleagues, and gratitude to Dr. Narasimhan and his colleagues for maintaining production despite COVID-19.


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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Wednesday, August 19, 2020

Fw: (LML) a change in our thinking about the disease leprosy and its epidemiology

 


Leprosy Mailing List – August 19,  2020

 

Ref.:  (LML) a change in our thinking about the disease leprosy and its epidemiology

 

From:  Ben Naafs, Munnekeburen, the Netherlands


 

 

Dear Pieter,

 

In answer to the questions of dr Laila de Laquiche, in LML 16th of this month.

 

Thank you for your reaction and I do not know where the line between a healthy carrier and a subclinical patient is. When the bacilli multiply without clinical symptoms, I would call it a subclinical disease. But the "damage" done before to a nerve, which is subclinical, I do not know how to call. There may be, or not be, serological tests which show contact with antigens. Contact with DNA may be shown with PCR but when there is no multiplication too me it is not the subclinical infectious disease: leprosy. May be, you just must call this kind of damage:  Subclinical M. leprae antigen related nerve damage (Su.ML.Rel. ND). Cannot think of a single word.

 

Concerning your doubt: like in Convid-19, tests at present may confuse clinical reasoning. But if we know which parameter goes together with the multiplication of M. leprae and we can test for that parameter it will be a real contribution. For the time being all immunological tests will only help for classification and may be detection of reactions and may be useful for epidemiological research.

 

I hope it answers some if your questions. The questions help me to make my concept clearer for myself.

 

Thanks a lot, I hope more people will contribute. May be to say and explain why it is rubbish.

 

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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Tuesday, August 18, 2020

Fw: (LML) Lack of MDT in Brazil

 


Leprosy Mailing List – August 18,  2020

 

Ref.:  (LML) Lack of MDT in Brazil

 

From:  Claudio Salgado, Belém, Brazil


 

 

Dear Pieter,

 

Last week, the Brazilian Society of Hansen's Disease (SBH) received from its representative in Northeast Brazil, the colleague Francisco Bezerra de Almeida Neto, an important and serious information about the lack of multidrug therapy (MDT) in the country.


The lack of MDT, now officially revealed in the state of Pernambuco, has been reported sporadically in different social media groups that I participate in, at different times in the year 2020 and in different municipalities, including within the closed group of SBH members. What appeared to be restricted to some Brazilian municipalities causes us to anguish now due to the uncertainty of a possible dissemination of the problem to the other States of the Brazilian Federation. Other entities, such as the Movement for the Reintegration of People Affected by Hansen's Disease (MORHAN), also report similar problems in other cities around the country.


Also, according to the Dr. Almeida Neto document, the production of MDT was maintained even during the COVID-19 pandemic, precisely to avoid the lack of MDT for leprosy patients (as disclosed on the web at https://zeroleprosy.org/novartis-kalwe-site-associates-mdt-covid19/). The lack of MDT can cause serious problems not only for the patient itself but also for society in general.


Individually, the untreated patient will evolve with the natural history of the disease to physical disability, perpetuating the stigma of leprosy and prejudice in society, which will be affected by the maintenance of the chain of transmission of the disease. It is also necessary to consider social, economic, emotional, and financial losses due to the lack of medications, not only MDT, but also second-line antibiotics.


While SBH is in solidarity with leprosy patients who are currently not being treated, we request that the Ministry of Health publicly make available the number of drugs scheduled and delivered to the states in 2020.  Besides, it is essential to know the quantity in stock and the quantity of MDT or second-line drugs that will still be received or purchased by the Ministry of Health this year. In this way, society can verify whether the quantity is enough, less, or even greater than the needs of each Brazilian state.


Considering the reach of a high number of experts on the Leprosy Mailing List, I would like to ask here if there are other countries with similar problems, and if there is availability of second-line drugs on the many parts of the world where Hansen's Disease is still notified?

 

Best regards,

 

Claudio Salgado

President SBH

Full Professor

Pará Federal University, Brazil


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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Sunday, August 16, 2020

Fw: (LML) a change in our thinking about the disease leprosy and its epidemiology


 


Leprosy Mailing List – August 16,  2020

 

Ref.:  (LML) a change in our thinking about the disease leprosy and its epidemiology

 

From:  Laila de Laquiche, Parana, Brazil


 

 

Dear colleagues,


The comments of Prof. Naafs in the LML of the 10th of August made me think of the story of Mary Mallon: healthy carrier of Typhoid Fever.

 

What will be the turning point between the healthy carrier and the subclinical patient in Leprosy? What's the definition of disease? Much to learn in Leprology; I have this doubt that haunts me. 

 

Would advances in diagnostic tests be enlightening or a confusing factor in clinical reasoning? 

 

Prof. Naafs thanks for instigating and always making us think about the pathophysiology of the disease!

 

Best regards!

 

 

Os comentários na LML do dia 10 de Agosto fez-me pensar na história de Mary Mallon: portadora saudável de Febre Tifóide...

 

Qual será o "divisor de águas" entre o portador saudável e o doente subclínico na Lepra?

 

Eu que tenho ainda muito a aprender em Leprologia, tenho esta dúvida que me persegue.  Os avanços dos exames diagnósticos seriam esclarecedores ou um fator de confusão do raciocínio clínico?

 

Obrigada por instigar e fazer-nos pensar sempre na fisiopatologia da doença.

 

Cordialmente,

 




Enclosed annual report 2019 of the Alliance Against Leprosy


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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Saturday, August 15, 2020

Fw: (LML) INFORMA HANSENÍASE (iH)



Leprosy Mailing List – August 15,  2020

 

Ref.:  (LML) INFORMA HANSENÍASE (iH)

 

From:  Patricia Deps, Vitória, Brazil


 

 

Dear Pieter.

I would like to introduce you and your colleagues to the INFORMA  HANSENÍASE (iH) project.
 

  • INFORMA HANSENÍASE is an educational project based on the production and dissemination of information about Hansen's disease for academics, researchers, health care workers, persons affected by Hansen's disease and the general public. It is also a project for the dissemination of ideas and good actions targeted at Hansen's disease and the community.

 

  • INFORMA HANSENIASE has a website www.infohansen.org, a YouTube channel and social networks. It is intended for the dissemination of diverse content through electronic books, scientific articles, essays, opinion, and points of view. We have a space for the community - "I want to hear your voice" - to publish interviews, a virtual exhibition, community service, and a board for information about events.


The iH team:
 

  • We are a team of volunteers, professors and students from the Federal University of Espírito Santo who organized ourselves into groups commissioned to produce quality content on the theme chosen for each edition.


The aim of iH:
 

  • We want to spread the word about what is being done in Brazil and the world to improve the lives of persons affected by Hansen's disease, together with new scientific findings and ethical reflections.


The iH launch content:
 

  • We have opened several channels of communication with people from all over the world and we are striving to have information published whenever possible in four languages: Portuguese, Spanish, English and French.

 

 

  • The theme of our first edition of INFORMA HANSENÍASE is stigma.

 

 

 

  • In the Community space - I want to hear your voice - we will show stories of two persons affected by Hansen's disease, and talk about the experience of a child who was separated from his parents by the segregationist health policy of the 1960s.

 

  • Interviews with the UN Special Rapporteur on the Elimination of Discrimination against Persons Afflicted by Hansen's disease, recounting her experience in combatting stigma, and setbacks to Hansen's disease control programmes in Brazil and other countries during the COVID-19 pandemic.

 

 

  • I would also like to highlight the contribution from MORHAN's vice-coordinator, who recalls in a creatively-written text the sad moment of his diagnosis, which also includes tips for health professionals about what not to do during the process of communicating bad news to a person diagnosed with Hansen's disease.

 

 

  • We introduce the Committee for Assistance to the Brazilian Immigrant Afflicted by Hansen's disease - CAIBAH, and invite colleagues and institutions in the international community to build the support network in several countries.


The iH invitation:
 

  • Our project is open to your collaboration, if you have a story to tell us, want to write us something - article, presentation of your book or thesis, interview, display your photos or want to propose us something new, please contact us. 


We will soon announce the theme of the next edition.

For official information about the project and the Brazilian participants, please access the link: https://projetos.ufes.br/#/projetos/1780/informacoes

An editorial about the project is attached in Portuguese, French and Spanish.
 

 

Patricia D. Deps (MD, MSc, PhD)

Full Professor
Medical School and Posgraduate Programe in Infectious Diseases
Federal University of Espirito Santo
Vitória-ES-Brazil
patricia.deps@ufes.br
+55 27 99999 6390
 

 

Patricia D. Deps
Dermatologista
Professora Titular
Departamento de Medicina Social
Programa de Pós-Graduação em Doenças Infecciosas
Centro de Ciências da Saúde
Universidade Federal do Espírito Santo
Vitória-ES-Brasil

ORCID https://orcid.org/0000-0002-9707-1934
CV Lattes: http://lattes.cnpq.br/9820695143683631


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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