Leprosy Mailing List – May 22, 2021
Ref.: (LML) The world's most impactful intervention against HD (leprosy) transmission
From: Joel Almeida, London and Mumbai
Dear Pieter and colleagues,
The measured outcomes and impact of the mass multi-drug administration with ROM (rifampicin + ofloxacin + minocycline) in FSM (Federated States of Micronesia), are the best ever achieved. An 84% decline in new HD cases was achieved within 2 years. Those who received ROM showed a 92% reduction in incidence rate of HD compared to those who did not receive ROM. The intervention was discontinued prematurely. However, when all deliberate interventions against HD (leprosy) are analysed throughout history, this ROM intervention in FSM emerges as the most impactful. No segregation was involved. We gained important clues about what is achievable..
What were the elements of the intervention?
a) Polar LL (lepromatous) patients received prolonged anti-microbial protection, beyond 12 months of MDT. This protected them against re-infection and very painful ENL (Erythema Nodosum Leprosum) episodes.
Prolonged anti-microbial protection (MDT beyond 12 months) was a critical component of the success. Otherwise polar LL patients are forced to accept re-infection. Simply protecting polar LL patients against reinfection (in endemic areas) is capable of achieving a sustained 16%/year to 20%/year decline in new LL and MB (multibacillary) HD cases. This was demonstrated in Karigiri (a low income population, India) and Shandong (China) in the 1980s. Karigiri then switched from prolonged anti-microbial protection to 2 year and 1 year MDT (multi-drug therapy) in the 1990s. This again allowed the polar LL patients to be reinfected after MDT. Recurrent LL HD is an important source of concentrated viable bacilli, and the near-zero incidence rate of LL HD was lost. Yunnan (China) always used only 2 years or 1 year of MDT. Despite steady increases in income levels and "HD villages", Yunnan is still achieving only about 6%/year decline in new HD cases. This is a much slower decline than Karigiri or Shandong.
Reinfection of polar LL patients allows the bacilli to cause hard-to-diagnose recurrent HD and to keep infecting children and others. It also multiplies the risk of excruciatingly painful ENL episodes among the polar LL patients, driving some of them to suicidal ideation. In FSM, the end of the project was accompanied by the switch from prolonged MDT to 1 year MDT for even LL patients. This allowed the bacilli to cause recurrent HD and so to maintain a supply of highly concentrated viable bacilli. This problem can be solved simply by prolonging MDT for polar LL patients who rely on free-of-charge MDT, or by offering monthly post-MDT chemoprophylaxis with 3 bactericidal drugs to LLp patients who can afford to pay. Sub-polar LL patients respond well to MIP vaccine, and 24 months of MDT probably suffices for them once they receive such immunoprophylaxis. But polar LL patients in an endemic area require prolonged protection against ENL and bacillary proliferation, regardless of immunoprophylaxis.
b) Polar LL patients were diagnosed during skin camps, for all skin conditions, with experienced clinicians assisting less qualified personnel. This reduced the number of missed LL patients.
Polar LL patients can shed tens of millions of viable bacilli per day, but too often show few or no visible signs of HD. Microscopy of skin smears or nasal smears shows globi packed densely with acid-fast bacilli. Expert clinicians know how to detect the subtle physical signs even while waiting and campaigning for microscopy services to be restored. Participation of an expert clinician was a critical component of the success in FSM/ROM. Otherwise, even a single missed LL patient is forced to keep spreading millions of viable bacilli per day, infecting children and others.
This problem can be solved by encouraging experienced clinicians to participate in skin camps, and having smear technicians travelling from camp to camp to collect nasal or skin smears for transport to a quality-controlled microscopy centre. Experienced clinicians have busy lives. But in India many clinicians donate some of their valuable time to this noble cause. Telemedicine allows experienced clinicians to assist in even remote, hard-to-reach areas. Perhaps more formal arrangements and reasonable compensation can be offered to experienced clinicians for participation in integrated skin camps. Skin camps deal with all skin conditions, not just HD. Therefore they also help reduce stigma.
c) ROM was offered at intervals to everyone in this high endemic area. This is now called mass multi-drug administration. It is used for many diseases, and repeated relentlessly at intervals until transmission is interrupted.
Mass multi-drug administration was a critical component of the temporary success in FSM. Nearly all sources of concentrated viable bacilli were shut down temporarily. The impact was immediate. The use of a multiple drug combination delayed the selection of drug-resistant mutant bacilli.
When would be the right time to withdraw such an intervention? After no child case was detected for several years. Two annual rounds of ROM was too short for lasting victory.
What would be the right frequency for mass multi-drug administration? Probably more frequently than once a year. Every 9 months, and in hyperendemic "hot spots" even more frequently. Probably every 6 months.
What would be the most convenient way to administer it? Probably together with skin camps and mass drug administration (MDA) for other diseases. Many of the MDA diseases co-exist in the same populations, and campaigns of MDA are already in operation in several HD-endemic countries.
In summary, the components that enable 84% reduction of new HD cases within 2 years are:
1) Prolonged anti-microbial protection for polar LL patients, to interrupt transmission at source
2) Expert skin camps for all conditions, aided by smear microscopy, to detect even those previously undiagnosed polar LL patients who have only subtle signs of HD
3) Mass multi-drug administration using ROM or equivalent at intervals of less than a year, to reduce the incidence rate of HD to near-zero levels within a very short time. All the complications of HD, from disfigurement to painful ENL to social exclusion, are therefore avoided.
Financing
What would be the best way to raise financing for such highly impactful campaigns? Probably to do what we did for TB at WHO in the 1990s, when TB was under-financed with only about 100 million USD annual financing globally. Now TB has been adopted by the whole world as a major initiative with billions of USD in annual financing. HD is not a killer, and most people are naturally immune (unlike in TB). The investments required are correspondingly lower.
What did we do, as the small WHO TB team in the 1990s?
We identified the most impactful intervention (which we defined as the DOTS strategy). Then we set up demonstration projects in endemic countries. When great measurable outcomes were shown repeatedly, the governments and donors all became enthusiastic about contributing finance to spread the great outcomes. Money chases great outcomes.
(In HD, by contrast, some organisations have been trying to promote demonstrably ineffective and harmful interventions that are far inferior to the FSM ROM intervention, and less effective even than MDT given till smear negativity. It would be good to avoid single drug use that can increase drug-resistance and drag us back to the days of hard-to-treat HD.)
The best outcomes are available from the Sasakawa Health Foundation (SHF)/WHO intervention in FSM. This demonstrated dramatic, rapid impact. It is the kind of success that can start a snowball of great outcomes, great impact, attracting adequate investment to spread the success everywhere.
Starting the snowball of success
Where would be a good place to demonstrate such rapid success? Perhaps former "HD colonies" are prime locations for once again demonstrating the impact of mass multi-drug administration used together with integrated skin camps and prolonged MDT for those with LL HD. Too many of these colonies suffer anti-microbial neglect and become hyperendemic "hot spots" where people still experience the excruciating pain of ENL episodes plus recurrent HD. Such settlements rapidly could become examples of "near zero transmission". No child who lives in such a colony need develop HD, and nobody here who has experienced HD need develop avoidable disability or suffer neglect. Former "HD colonies" could become beacons of "zero transmission", zero neglect, zero new sequelae, free from extreme poverty and emboldened to advance socio-economically with full participation in mainstream life. Demonstrable success is the best answer to scepticism, as we found in TB. Former "HD colonies" that have a high incidence rate of HD could become islands of success. This success can spread to hyperendemic "hot spots" across the globe.
Finance for exemplary demonstration projects is already available from some noble-minded philanthropic organisations. As dramatic successes accumulate, governments of endemic countries tend to become enthusiastic about investment. There is no reason for delay.
Avoiding drug resistance
It seems important, however, to avoid drug resistance. It has compromised efforts in TB greatly. We need not let drug resistance derail our victory in HD. We aim for the mountain-top of zero HD transmission, but we walk along the cliff-edge of drug resistance. It is easy to push endemic countries over the edge by using or promoting single drug use (e.g., promoting SDR PEP instead of the highly impactful SHF/WHO ROM intervention). We are all life-long students, open to learning from unexpected disappointments and unexpected successes alike. It would be good if all of us could learn from this impactful and world-leading SHF/WHO ROM intervention.
Conclusion
It seems sensible to use multi-drugs invariably, instead of single drugs, whether for prophylaxis or treatment. The SHF/WHO ROM project in FSM shows that we can succeed, and rapidly, while delaying drug resistance. We too can achieve 84% decline of new HD cases within 2 years. We could implement this mass multi-drug intervention relentlessly in hot spots, until every child is free from the threat of HD transmission. In other areas a 20% annual decline in the incidence rate of MB HD is available by ensuring prolonged anti-microbial protection for polar LL patients.
A world with near-zero HD transmission is within our reach, providing we avoid drug resistance. Let's open our minds, learn from programmes with huge epidemiological impact, and reach for success.
Joel Almeida
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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