A pilot assessment of miltefosine's efficacy and tolerability for treating cutaneous Leishmania tropica in Afghanistan

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Cutaneous leishmaniasis (CL) is a skin disease that has been around since biblical times. The disease is caused by the leishmaniasis parasite, which is transmitted by sand flies between humans or between small animals or dogs to humans. Historically, CL is divided into Old and New World leishmaniasis (OW or NWCL). OWCL stretches from the Mediterranean Sea, across the Middle East and Caucasus region, to western India. There are also affected areas in east and west Africa. NWCL is found in Mexico, central and most countries in South America (except Chile, Argentina and Uruguay).The World Health Organization (WHO) estimates that the number of CL cases per year in the world is 600-900,000 with 90% occurring in seven countries: Afghanistan, Algeria, Brazil, Iran, Peru, Saudi Arabia, and Syria. CL thrives where there is poverty, war and large population displacements. This is particularly the case in Syria and Afghanistan. CL results in ulcers, nodules, and dry scaling of the skin especially on the face which patients find upsetting. NWCL may also invade the mouth, nose and throat leading to a more unsightly and severe disease. This form is rare in OWCL but has been reported in Syrian refugees because they have not been able to receive early treatment. Treatment for CL is limited to toxic drugs because there is little interest by drug companies and governments to conduct research. This is why leishmaniasis is a WHO-designated neglected tropical disease. We plan to conduct a small pilot study to see if a drug called miltefosine is effective in OWCL in Afghanistan. Miltefosine is effective for treating visceral leishmaniasis (leishmaniasis affecting our internal organs) and some types of NWCL. It can be given by mouth, a big advantage over currently used treatments, but over 28 days which may be a challenge for patients. In Afghanistan, CL is caused by the Leishmania tropica species which is transmitted between humans. This explains the high number of cases in Afghanistan and Syria and why the WHO recommends treatment. Sodium stibogluconate (SSB) is the only drug available for treating CL in Afghanistan. It has to be given over 20 days by injection into the skin, vein or muscle which is painful and distressing, especially for small children who make up about 25% of cases. SSB is toxic and may affect the liver, kidneys, pancreas, blood, and heart. As a result, some patients have to stop it early. Better alternatives are needed. Our pilot study will give miltefosine and SSB, using recommended doses, and follow patients for six months to see if their skin is cured; a long follow up is needed because CL can return even though the skin appears healed. We will also measure miltefosine levels in the blood and the leishmania parasites in the skin over time and examine the relationship between the two. This has never been done before for L. tropica. We will also ask patients about their knowledge of CL, how it affects their life, and how much they are willing to pay for a treatment that they prefer to SSB. If our study shows miltefosine has promise, we will apply for more money to do a large study comparing 14 and 28 days of miltefosine with SSB. A large study will give us confidence in the results. We are willing to accept a lower miltefosine cure rate (e.g. 5-10%) over SSB if it is more popular with patients. If 14 days of miltefosine is also very effective, this would be a big plus because miltefosine is expensive; the WHO price is about 70 and 100 pounds for children and adults, respectively. Having an effective and popular oral treatment, especially over 14 days, would be so much more convenient for clinics and patients and will improve access to treatment for many people with OWCL.