Summary Leishmaniasis is an emergent protozoan disease that afflicts over 12 million people worldwide. After years of working in proximity to the Leishmania parasite, I contracted Leishmaniasis for the first time this year. In this post I share my experience. First, based on my own parasite’s species ID, the geographic ranges of Leishmania appear poorly known. This biogeographic ambiguity does impact diagnoses. Second, treatment in the U.S. is outrageously expensive (>$56k for 84 miltefosine pills), even though public funds paid for much of the R&D. I invite others to share their experiences with Leishmaniasis as a way to spread awareness of the disease and the political factors that keep effective treatments out of the hands of many.
As an intern for the Biological Dynamics of Forest Fragments Project (BDFFP) in the early 1990s, I heard frequent warnings about Leishmaniasis. Leishmaniasis is caused by protozoa (genus Leishmania) that are transmitted to people by phlebotomine sand flies. Like sperm penetrating an egg, flagellate Leishmania enter and reside in the infection-fighting macrophages around wounds. In cases of cutaneous Leishmaniasis, skin wounds expand instead of heal. During the 1990s about one fourth of the long-term workers at BDFFP had contracted cutaneous “leish” (rhyming with rice in Portuguese). It seemed most frequent in disturbed areas and tree canopies where sand flies abound. During my internship and subsequent PhD work I was bitten by hundreds of sand flies – the bite feels like a pinch and leaves a distinctive red mark (see first photo in gallery).
Fast forward 25 years. I returned to the BDFFF in February, this time with Brazilian and U.S. students, to carry out research on the Brazil nut family, Lecythidaceae. We worked in the undisturbed “Km 41” research site in February this year.
On my return to Michigan I received an “alert” email highlighting 4 recent cases of Leishmaniasis at BDFFP. At the same time, I noticed that a sore on my right hand was not healing (see middle photo in gallery) coincidentally (or not) near previous sand fly bites. I met with U-M infectious disease specialists. Based on the geographic ranges of the Leishmania species (see Fig 1) I could have been exposed to L. panamensis, L. guyanensis or L. amazonensis – species that cause cutaneous Leishmaniasis. My doctors advised me to watch the sore. It it was not leish it would just go away. If it was cutaneous leish my body might just heal naturally.
I was fortunately out of the range of L. braziliensis, which can cause mucocutaneous leishmaniasis — or so we had thought. This is an aggressive species that can spread to the mucosal lining of the nose and mouth and in rare cases cause severe disfigurement and death. The range of L. braziliensis was hundreds of kilometers away in the western and eastern Amazon (see figure 1) somehow avoiding central Amazonia (central Amazon + Guyana). (I found out later that L. guyanensis can also cause mucocutaneous Leishmaniasis)
My sore didn’t heal, and a biopsy showed protozoan-like bodies consistent with Leishmania. Tissue samples were sent to the CDC for genetic assays. To my surprise they were identified as L. braziliensis.
Treatment has improved a lot since the 1990s. The older antimony-based treatments took months and dozens of injections, often damaging liver and kidney function. The preferred treatment at U-M is an experimental cancer drug called miltefosine (trade name Impavido) that has the important side effect of killing Leishmania and some other protozoans.
I took the miltefosine (Impavido) prescription to my local drug store and was told “this is above our pay grade” – I’d have to go to specialty pharmacy. It took three weeks working through several intermediaries to get the drug — time that I could have used treating the parasite. The problems were supply and price. It was understocked, and my 84-capsule treatment cost ~$56,000 (my copay was $20, but this is often not covered by insurers). Knight Therapeutics has an agreement to provide Impavido at a reduced price to developing countries. That price is $5.25 per pill (compared with $666 per pill in the U.S.) (Sunyoto et al. 2018).
Why is miltefosine so astronomically expensive? This question is answered in an recent paper by Sunyoto et al. (2018). The concise answer is that Knight Therapeutics has a monopoly over the distribution of miltefosine, so they can charge whatever they want (see related Epipen price scandal). The main consumers of miltefosine in the U.S., besides tourists (see this post) and the occasional tropical biologist, are U.S. veterans returning from the middle east with Leishmaniasis.
I ended my 28-day treatment last week. The side effects included heartburn and nausea, which got worse toward the end. In week 3 I had a swollen foot and thought that I might have broken a toe without knowing it. This was diagnosed as gout (uric acid crystals in the foot joints) that the doctors suspect was caused by the drug. I had two flare-ups of gout, which caused me to limp around campus for a few days. Because of the treatment, I also missed out on doing summer fieldwork in Brazil.
All the while I was dealing with my case, a grad student down the hall was getting treated for L. braziliensis that he had contracted in Peru in December 2017. Peter Cerda‘s symptoms were far worse than mine, as his parasites became systemic and moved from his leg to his face. His 200 mg/day $74k miltefosine treatment did not work (Note: Soto and Soto (2006) report a 35% success rate in treating L. braziliensis in Guatemala). He followed the miltefosine with an intravenous treatment using the antifungal drug ambisome, which now seems to be working.
I’ll be returning to forests that contain Leishmania again (in Brazil, Ecuador and Panama). However, next time I will cover up better (i.e. long sleeved shirts, gloves), lather up with insect repellent, and use a mosquito net around my hammock.
When I posted my story on Facebook I found that many of my friends have dealt with Leishmaniasis over the years, using different kinds of treatments. Their experiences were in most cases more dire than mine. I invite you to share your experiences about Leish in the comments. Where did you contract it? What treatment was prescribed, and how did you respond to the treatment? Is Leishmaniasis on the rise at your field station?
Acknowledgements — thanks to the excellent doctors at U-M who took a special interest in my case. Thanks also to Dr. Naomi Aronson who answered my questions about her 2017 paper. Dr. Aronson is actively researching a vaccination for Leishmaniasis. The papers below are all open access.
Aronson, N. et al. (2017) Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clinical Infectious Diseases 2016:63
Soto, J., and P. Soto (2006) Miltefosina oral para el tratamiento de la leishmaniasis. Biomédica 26(Supl.1):207-17 (abstract in English)
Sunyoto, T., J. Potet, M. Boelaert (2018) Why miltefosine—a life-saving drug for leishmaniasis—is unavailable to people who need it the most. BMJ Glob Health. 2018; 3(3): e000709.