Global scabies control: An interview with Andrew Steer and Lucia Romani

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David Flood
David Flood, MD, MSc, is a physician with the Guatemalan NGO Wuqu' Kawoq | Maya Health Alliance and resident in Medicine-Pediatrics at the University of Minnesota. He received his medical degree from Harvard Medical School and an MSc in international health policy from the London School of Economics.
Scabies illustration from a 1904 medical textbook. (Image rotated and cropped; source.)

Scabies illustration from a 1904 medical textbook. (Image rotated and cropped; source.)

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Andrew Steer

Andrew Steer is a pediatric infectious diseases physician at the Royal Children’s Hospital in Melbourne and a senior researcher at the University of Melbourne and Murdoch Children’s Research Institute. Lucia Romani is a PhD candidate in epidemiology at the University of New South Wales who has been involved in research on scabies control since 2007. In December 2015, they and their co-authors published in the New England Journal of Medicine the results of the SHIFT trial. Using an “elegant randomized [design] involving island communities in Fiji,” they demonstrate the high efficacy of ivermectin-based mass drug administration in reducing scabies infections and complications in a population with endemic disease.

What was the background history of the trial you conducted?

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Lucia Romani

Lucia Romani: My involvement started in 2007 when I met a dermatologist in Sydney named Margot Whitfeld, as well as Andrew Steer, who were trying to determine the prevalence of scabies in Fiji. During a workshop in Fiji, the majority of local doctors and nurses named scabies as the main health problem they were facing in their day-to-day clinical practice. Dr. Whitfeld became interested in this problem. The Fiji Ministry of Health suggested conducting a national study to understand the burden of disease, which we carried out in 2007. We surveyed over 10,000 people across the country, and we found a scabies prevalence of about 24%–and approximately 50% of children having the disease. We presented the data to the Ministry of Health and began thinking about finding a solution to control scabies. And the SHIFT trial [Skin Health Intervention Fiji Trial] was born.

Andrew Steer: We did some other studies as part of our National Institutes of Health grant to look at Group A Strep disease in Fiji. One of them was looking at the incidence of skin infections. We had a cohort of 450 children that we followed over a ten-month period. Essentially, we found that 50% of kids in a year would get a new episode of scabies; that’s a huge burden. We also developed some guidelines to add on to IMCI [Integrated Management of Childhood Illness], validating a skin disease algorithm to go within the existing IMCI program in Fiji and also taken up in other Pacific Island countries.

We know that we could provide guidelines for treatment, but even if those guidelines were followed, our concern was that the children would go back to their schools or homes—where other people infested with scabies lived—and the cycle would just start again. That’s where this idea of mass drug administration (MDA) came. A study by David Taplin and colleagues in Panama from the early 1990s very nicely showed that mass administration with permethrin could bring down prevalence. We also knew from a study in the Solomon Islands that ivermectin could also work. But the two had never been compared. So that’s the thinking behind the SHIFT trial.

Scabies causes intense itching that can affect sleep and quality of life, but it has other complications too. Andrew, can you explain those from your perspective as an infectious disease doctor?

AS: In endemic areas, scabies skin infections are a very common portal of entry for bacteria. The two main bacteria are gram positives like Staph aureus and Group A Strep (or Streptococcus pyogenes). This often leads to impetigo, which is a superficial bacterial skin infection. We have shown from our studies that scabies is a very important risk factor for impetigo, and we found in the SHIFT trial that when you get rid of scabies that you also reduce the prevalence of impetigo by about two-thirds. And then impetigo can turn into severe skin and soft tissue infections with those bacteria, which are very common in tropical areas. The bacteria can cross into the blood and cause dangerous bloodstream infections and invasive bacterial infections. Additionally, scabies outbreaks are associated with impetigo outbreaks leading to endemic glomerulonephritis, which contributes to end-stage renal failure in tropical countries. And there is circumstantial evidence that the Group A Strep in skin from scabies infections contributes to rheumatic heart disease.

Scabies under the microscope. (Source.)

Scabies under the microscope. (Source.)

Your results in the ivermectin arm showed a relative decline in scabies prevalence of 94% and in impetigo of 32%. Did these outcomes exceed your expectation when you designed and conducted the trial?

AS: We had conservative estimates for the purposes of sample size calculations. Still, it would be fair to say that we were thrilled with the results. In the ivermectin arm, the results are consistent with what had previously been seen in the Solomon Islands trial. But the great value is that, for the first time, in a controlled way, we were able to compare mass administration of ivermectin with standard of care and with permethrin. We provide evidence that this oral medicine is superior to other interventions.

In a separate, long-term follow-up study of that Solomon Islands trial, you showed that ivermectin might even have the potential for long-term scabies control, or near-eradication.

AS: That study is really interesting. The obvious limitation is that we don’t really know what happened in the intervening 15 years between 1997-2000 when the mass treatment with ivermectin was administered and 2015 when we did our follow-up study. But it is fascinating to think that a relatively simple intervention might lead to a long-term reduction in scabies. So that’s really important research question: What is the durability of mass drug administration of scabies on long-term outcomes?

The SHIFT trial found that the prevalence of scabies initially declined from baseline when ivermectin was administered to 3 months. But then prevalence declined even further from 3 months until 12 months even though no further treatment was given. What do you make of this finding?

AS: It was a little surprising. There is the concept that you treat the mite, the mite goes way, but you’re left with an inflammatory response. And the duration of the inflammatory response is not well described but can certainly last 3 months. I guess that’s why the 12-month outcome measure was a good choice because none of that potential confounding measurement would be present. The other thing about that 3-month measurement was that it was only 20% of the population, so although the population was randomly selected there was some skewing in the standard group towards younger male children in whom scabies is more common. So I think we have to take it with a little bit of a grain of salt and really focus on the primary outcome measure at 12 months.

In my experience, there are significant practical challenges with clinical treatment of scabies with topical agents like permethrin cream or benzyl benzoate. What are your thoughts on the advantages of using an oral drug like ivermectin? 

LR: It was a challenge even in our study in Fiji to get kids and parents to apply the permethrin cream because it has to be applied from head to toe and be left on for 8 hours. And you can imagine how hot and humid it can be in Fiji! I certainly wouldn’t be too keen on the cream myself. An additional advantage of oral ivermectin is that Fijians are very familiar with the concept of oral mass drug administration because they already do that with the lymphatic filariasis program. It wasn’t difficult to consent people to take ivermectin.

Patients waiting at a health clinic in rural Guatemala, one of many global settings where scabies is endemic. (Photo from Rob Tinworth.)

Patients waiting at a health clinic in rural Guatemala, one of many global settings where scabies is endemic. (Photo from Rob Tinworth.)

Had ivermectin been used for lymphatic filariasis before in Fiji?

LR: No, for filariasis, Fiji uses a combination of albendazole and DEC (diethylcarbamazine). Ivermectin wasn’t used before our study.

AS: That’s actually one of the things that got me thinking about ivermectin for scabies was my first foray into the Pacific to Samoa in the mid 1990s. When I was there, I did a small survey of skin disease in schools. The year before, there had been an MDA for lymphatic filariasis that included ivermectin. What was fascinating was that the prevalence of scabies was very low, and the people in the villages were telling me how they used to have lots of itchy scabies but that it went away with the MDA for lymphatic filariasis.

You are both involved in global scabies control efforts through your work with the International Alliance for the Control of Scabies (IACS). What kind of feedback have you received after SHIFT was published regarding scaling-up ivermectin therapy within communities and health systems?

AS: One of the things that has happened since SHIFT’s publication is that we are finishing another study called AIM. I can’t give you the results yet, but I can tell you what the study is about. AIM stands for “azithromycin-ivermectin mass” drug administration. We’ve conducted the study in collaboration with the Solomon Islands’ Ministry of Health, which has been running a trachoma control program with azithromycin. We essentially piggybacked on the MDA infrastructure for trachoma with an ivermectin-based MDA in a population of over 26,000 people in September 2015. The primary outcome of that study is the feasibility and coverage, and we’re still analyzing the data. But I think the approach in this study speaks to one way of integrating MDA public health delivery, monitoring, and evaluation not only for one vertical disease program but across multiple programs.

The WHO now considers scabies a neglected tropical disease (NTD). At the same time, as explained by the New England Journal editorial accompanying your article, there is no formal roadmap for scabies control like with other NTDs. What’s the way forward? 

AS: There are a few jobs for IACS. One of them is thinking about that roadmap on a global level, and also providing resources for ministries of health and other interested parties to move forward for scabies control. There are things like diagnostic criteria for field assessments, for example, among many other resources that IACS is working towards.

Lucia, how did you become involved in scabies research?

LR: As I mentioned, since 2007 I’ve been involved in public health control of scabies in the Pacific region, mostly in Fiji and the Solomon Islands. I’m a PhD student due to finish in March.

Congratulations! My last question for you is that we’ve discussed the paradigm of mass drug administration for scabies, lymphatic filariasis, and trachoma; are you interested in other diseases for which this model might be an effective strategy?

AS: We’ve been very interested in integrating public health control of skin diseases. We organized a symposium at the American Society of Tropical Medicine and Hygiene last year in Philadelphia on this theme. One of the challenges is bringing the groups together, and we’ve had some conversations with the Strongyloides group, for example, which is also a potential target for MDA ivermectin. This is another important topic as this area moves forward.