Fw: (LML) Fact-based accounts are helpful in HD

 

Leprosy Mailing List – February 26, 2021

 

Ref.:  (LML) Fact-based accounts are helpful in HD

 

From:  Joel Almeida, London and Mumbai

 

 

Dear Pieter & colleagues,

The main opportunities for better healing and more respectful attitudes towards people affected by HD, from diagnosis to end of life, seem to flow from facts. Esteemed colleagues can feel free to improve this account.

1. A single, small, well-defined anaesthetic skin patch, with no enlarged nerves and no other signs of HD, typically predicts self-healing and non-infectiousness. In good conscience, such a person cannot be accused of spreading bacilli. 

Because this sign has a very short natural duration, it usually subsides spontaneously before the next case-finding campaign, without any sequelae. But frequent door to door surveys in endemic areas typically demonstrate it to be the most frequent sign. During the COVID-19 pandemic, the observed incidence rate of this sign is predicted and observed to fall dramatically. This is an artefact, attributable to less frequent surveys. Whenever the frequency of surveys increases, the observed incidence rate of this transient sign increases dramatically. This was predicted and observed during the intensive surveys in the years leading up to 2000, when the highest ever incidence rate of such signs was recorded. These transient signs are of much less consequence than types of HD that lack specific immunity and significant bacillary loads.

It seems desirable for a single small, transient, anaesthetic macule to be given a neutral, non-stigmatising label, even when brief treatment is given. In India, some enlightened professionals have been known to use terms such as "maculo-anaesthetic lesion", helping to shield people from ostracism, job loss, divorce, interruption of education etc.

 

Alongside such steps to protect persons with transient macules, it is still necessary to find and treat damaging types of HD before permanent deformity occurs. The pandemic has dealt a blow to those worthy efforts.

2. A complete contrast to transient macules is "de novo" lepromatous HD, so named because it arises without any earlier signs of HD. It is easily treatable with MDT. However, the signs are easily missed, because often there is no anaesthesia, no skin patches, and not even markedly enlarged or painful nerves. But a subtle induration of the skin is often discernible by experienced clinicians. Nasal smears or skin smears typically reveal astronomical numbers of acid fast bacilli. (1) The subtlety of signs suggest that the bacilli and the patient live in temporary harmony. Such patients, if left untreated, can shed tens of millions of viable bacilli per day in nasal discharges. The viability of bacilli in nasal discharges reduces spectacularly with the very first dose of MDT. Thereafter infectiousness remains at trivial or zero levels. This favourable situation continues for as long as LL patients are protected against reinfection. MDT, when continued beyond 12 months, protects against reinfection.

"De novo" LL disease does not self-heal. Such patients, if overlooked by inexperienced personnel, simply accumulate in the population. This is true especially where bacilloscopy is unavailable. Persons with "de novo" HD are frequently misclassified as being free from HD. Sometimes they are even pressed to take extremely short chemotherapy as prophylaxis. Such short treatment merely kills drug-susceptible bacilli. When a single drug is used, such as rifampicin on its own, the frequency of drug-resistant mutant bacilli is boosted among the surviving viable bacilli. Nasal discharges then pose a more sinister threat. That is why prophylaxis with single drugs is so highly dangerous. Drug resistance could again make HD a fearsome disfiguring disease that is difficult to treat. Drug combinations delay the selection of drug-resistant mutant bacilli, and therefore deserve to be used without exception. Always drug combinations, never single drugs.

Reinfected LL patients unprotected against bacilli, and "de novo" LL patients missed by inexpert personnel, are forced to continue shedding millions of viable bacilli per day, unknowingly. Bacilloscopy of nasal discharges shows densely packed clumps of acid fast bacilli.(1) BL patients, even before treatment, do not typically show such high concentrations of bacilli. Unprotected LL patients, before or after MDT, form the only known source of highly concentrated viable bacilli for people in endemic areas. Bacilli are an important driver also of ENL episodes, permanent nerve damage, serious disfiguration, and distressing socio-economic consequences. This is easily preventable, with the following practices:

a) Continued MDT, for patients with a high initial BI (eg., 4+ or more), beyond the customary 12 months. 

 

Alternatively, for patients who can afford it, monthly doses of bactericidal drugs in combination (eg., rifampicin + moxifloxacin + minocycline, or rifapentine + moxifloxacin + minocycline). Again, continued beyond 12 months. Some enlightened private practitioners and centres of excellence in India, Brazil and other endemic countries already use monthly doses of bactericidal drugs in combination, continued beyond 12 months.

b) More competent case-finding, with reliable bacilloscopy of nasal and skin smears.

Signs of reinfection/recurrence can be subtle. This explains the report that expert clinicians recognised reinfection/recurrence three times as frequently as well trained but less expert personnel. (2) Therefore, it seems wise to prevent reinfection by continuing MDT beyond 12 months in LL patients. The alternative is to allow the continued spread of bacilli to children and others, with the unprotected patients themselves suffering a greatly multiplied risk of ENL episodes.

Colleagues in endemic countries (eg., India and Brazil) see relatively many patients and are often astute clinicians. Expert clinicians running general skin camps are unlikely to miss "de novo" lepromatous HD. Teleconsultation is another important option for improving the quality of diagnosis by inexpert personnel. Governments and NGOs usefully could sponsor and compensate expert clinicians in endemic countries to devote part of their time to teleconsultations for people in poorly served areas. This will reinforce the ongoing worthy efforts to equip peripheral health workers with illustrated charts, online training, and mobile technology.


3. LL patients can be protected against re-infection also by reducing the main sources of bacilli in an area. Mass administration of a drug combination (eg, rifampicin + ofloxacin + minocycline, ROM, as was previously used in the Federated States of Micronesia) seems the most effective way of reducing sources of infection almost instantly, in a high endemic area. A 92% reduction in new cases of HD is demonstrable among those who received a single dose of ROM, by comparison with those who did not. (3) This was during the time when LL patients were allowed continuation of MDT beyond 12 monthly doses. Repeated mass multi-drug administration in high endemic areas (eg., every 6 to 9 months), when combined with MDT continued beyond 12 monthly doses for LL patients, is likely instantly to suppress nearly all human sources of bacilli. It is the surest known way to reduce transmission rapidly. Repeating the intervention at an intervals of months is much more effective than a single dose, because people are immediately re-exposed to infection after a single dose. With periodic mass multi-drug administration, children and others need no longer be exposed to astronomically high concentrations of viable bacilli. 

How about other sources of bacilli? Armadillos too are known to develop astronomically high concentrations of bacilli, on par with full blown LL disease in humans. Other extra-human reservoirs of bacilli have not been known to achieve such high concentrations of bacilli. In continents without armadillos, unprotected persons with LL disease are the only sources of highly concentrated viable bacilli. This maintains transmission. It explains why exemplary programmes which continued MDT till smear negativity achieved near-zero transmission, in even low income areas. 

 

Repeated mass multi-drug administration in high endemic zones can improve on those achievements. Mass multi-drug administration has been used successfully against lymphatic filariasis and other diseases, reducing transmission at hitherto unprecedented rates. HD need not remain excluded from such highly effective approaches. Nor is there any real justification for burdening low income countries with single drug use, with the accompanying selection of drug-resistant mutant bacilli. Multi-drug combinations, instead of single drugs, delay the selection of drug-resistant mutant bacilli.

Other diseases continue the search for re-purposed or new anti-microbial agents, and HD need not remain the exception. Multiple drug resistance is already upon us,(3) and closing our eyes is not a helpful response. The good work of testing drugs against M. leprae, continued sporadically in some centres, (4) deserves high priority.

 

 

4. Between the extremes of self-healing and relentless worsening (in the absence of treatment) are patients who require MDT as well as regular monitoring of nerve function. Otherwise the frequency of visible deformity increases from less than 10% of patients at diagnosis to more than 25% of the patients some years later. The demonstrable difference of over 15% in visible deformity arises owing to neglect of patients, especially during MDT. Skilled mobile teams travelling over a wide area can bring the necessary quarterly nerve monitoring to patients' doorsteps. They can also monitor and encourage the regular ingestion of MDT. It seems desirable for noble-minded NGOs to step in and provide these skilled mobile services, as was done formerly. Some NGOs and government services have resumed such skilled mobile services, with workers equipped with two-wheeled or four-wheeled vehicles. This allows early detection of nerve function impairment. Anti-inflammatory treatment can then be given promptly enough to restore and protect nerve function. Otherwise people continue to develop visible deformity despite early diagnosis and MDT. This unfortunately reinforces the public perception of HD as a dreaded, disfiguring disease. 

 

 

 

5.  The least fortunate persons affected probably are those excluded from family, community, mainstream opportunities, with visible deformity, suffering repeated reinfections and ENL episodes as a consequence, destitute, and abandoned by even health professionals. Many of these persons affected are invisible in even health statistics, wiped out of sight and out of mind. We have grown used to condoning, and occasionally even championing, anti-microbial neglect and wider neglect of such people. The pretext for neglect is that these people once received MDT. We usefully could enlarge our horizons beyond the killing of bacilli to the healing of people. Then we will start seeing the world more through the eyes of persons affected. That might well encourage us to act more effectively and humanely instead of abandoning people to reinfection, ENL episodes and nerve damage. A survey of destitute former HD patients, in two Indian towns, found positive skin smears in 17% of them.(5)

 

Persons affected want healing, inclusion and opportunities to make a good life. Not merely killing of bacilli, which are in any case invisible. Deformities are visible. A person whose bacilli are killed, who is well protected against reinfection because sources of concentrated bacilli have been shut down, who has escaped deformity, and in whose life HD has no long-term consequences, might well consider themselves healed.  We could widen our horizons to champion true healing. Ending the neglect of persons affected happens to be critical for ending transmission, because covert reinfection is frequent in endemic areas. But true healing is a worthy goal in itself, especially because it affirms the intrinsic dignity of every human being. 

 

 

Conclusion

More fact-based accounts allow informed actions while reducing baseless prejudices or harmful practices. We usefully could educate the public even as we keep improving our own understanding and practices. Our appeal and promise to the world could be along the following lines:

We are going to help restore the respect and inclusion that is due to every human being, including every person affected by HD. No more allowing people to languish without education, training, disability allowances, access to real opportunities. No tolerance for outdated laws that go contrary to the Universal Declaration of Human Rights, and run contrary to the UN Resolution on the elimination of discrimination against persons affected and their family members.

We are going to step up skin camps and other efforts to find persons affected by HD, to heal and protect them fully, testing and protecting their nerve function regularly, going beyond merely giving 12 months of MDT.

 

We are going to prevent drug resistance especially in low income countries by using multiple drugs always, and never single drugs. We are going to test a wider range of molecules against M. leprae in animal models, so that drug resistance will not defeat us.

 

We are going to end transmission of this disease that was formerly dreaded but is easily treatable and preventable using well-informed microbiology and epidemiology. This builds on the measurable epidemiological impact of MDT continued beyond 12 months, augmented with mass multi-drug administration in high endemic areas.

For the first time in history, we can be confident of freeing people and countries from transmission, disfiguration and devastating socio-economic consequences. The successes created at the frontline by great colleagues can be spread everywhere.

Joel Almeida

 

References

 

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

2. Cellona RV, Balagon MFV, dela Cruz EC et al. Long-term efficacy of 2 year WHO multiple drug therapy (MDT) in multibacillary (MB) leprosy patients Int J Lepr. 2003;71(4):308-19.,

 

3. Rosa PS, D'Espindula HRS, Melo ACL et al. Emergence and transmission of drug/multidrug-resistant Mycobacterium leprae in a former leprosy colony in the Brazilian Amazon. Clinical Infectious Diseases. 1 July 2019, ciz570, https://doi.org/10.1093/cid/ciz570

 

4. Arumugam S, Joseph P, Ponnaiya J et al. Murine Model to Identify Short Duration Alternative Chemotherapy for Leprosy. Indian Journal of Leprosy 2016, 88 (3): 159-76

 

5. 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

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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