**7. Photodynamic therapy on the treatment of old world tegumentary Leishmaniasis**

There are several reports on the literature dealing with the treatment of leishmaniasis by PDT [5,6,33,34]. The first report was conducted by Enk's group in 2003 [5,6]. Both studies reported the use ALA and MAL, combined with red light. These authors performed the treatment of 32 TL lesions from 11 Israeli patients. The diagnostic was accomplished by verifying the amasti‐ gote presence in direct smear from the lesions [5]. This work showed that about 96% of the lesions healed, leaving some mild scars and pigment in place of the old lesions. Just one lesion presented amastigotes forms after PDT. Gardlo *et al.* published the case of a patient, aged 34, with CL confirmed by histology. According to the authors, the patient developed resistance to the treatment with sodium stibogluconate and presented 10 lesions, which were treated five times with PDT and five times with paromomycin sulfate ointment [6]. The result obtained is similar to the previous work and showed that the five ulcers treated with PDT healed without signs of amastigotes, while two ulcers treated with paromomycin partially responded to the drug, one of them did not respond and two lesions were shown to have no amastigotes. The ulcers that did not responded to paromomycin ointment were subsequently treated with PDT successfully.

Asilian and Davami developed a placebo-controlled, randomized clinical trial that provided definitive evidence of the efficacy of PDT in the treatment of CL [34]. 60 patients with confirmed CL by clinical and parasitological diagnosis were separated in 3 groups with different treatments. Group 1 was treated with PDT once a week, group 2 received twice daily para‐ momycin plus methylbenzethonium chloride ointment and in group 3 was used a paraffinbased ointment without active ingredients with same application time of the group 2. During four weeks, the groups received the treatments described above. At the end of the study healing was present in 93.5% of the patients of group 1, 41.2% of group 2 and 13.3% of group 3. At the same time, 100%, 64.7% and 20% of the lesions had parasitological cure in group 1, 2 and 3, respectively.

Other studies accomplished in Iran and German corroborated with the results described above. According to the authors, PDT showed to have the capacity to treat wounds caused by Old Word *Leishmania* species. We emphasize that most of the reports claim that this therapeutical modality can achieve results above 90% healing of wounds, however, a caveat must be held since some of these studies indicate that not all healed wounds become free of parasite [35,56]. The mechanism of ALA PDT in the case of leishmaniasis was shown to be due to the killing of infected host-cell killing (macrophages) instead of direct parasite killing (see further discussion about this issue on section 8).

One CL case of the New World leishmaniasis is described in the literature. Song *et al.* reported the case of a Brazilian patient presenting cutaneous leishmaniasis confirmed by smear stained by Giemsa. PDT was carried out using MB. In this specific case because of ethical concerns of possible development of evolution to mucocutaneou disease, the patient received at the same time a low dose of pentavalent antimony and PDT. The patient had two ulcers. One receive PDT and the other was only being treated with the low-dose pentavalent [27]. The treatment

13

showed 100% of cure in both lesions, but the lesion treated with PDT presented a faster wound recovery compared to the antimony alone (Table 2).

**7. Photodynamic therapy on the treatment of old world tegumentary**

There are several reports on the literature dealing with the treatment of leishmaniasis by PDT [5,6,33,34]. The first report was conducted by Enk's group in 2003 [5,6]. Both studies reported the use ALA and MAL, combined with red light. These authors performed the treatment of 32 TL lesions from 11 Israeli patients. The diagnostic was accomplished by verifying the amasti‐ gote presence in direct smear from the lesions [5]. This work showed that about 96% of the lesions healed, leaving some mild scars and pigment in place of the old lesions. Just one lesion presented amastigotes forms after PDT. Gardlo *et al.* published the case of a patient, aged 34, with CL confirmed by histology. According to the authors, the patient developed resistance to the treatment with sodium stibogluconate and presented 10 lesions, which were treated five times with PDT and five times with paromomycin sulfate ointment [6]. The result obtained is similar to the previous work and showed that the five ulcers treated with PDT healed without signs of amastigotes, while two ulcers treated with paromomycin partially responded to the drug, one of them did not respond and two lesions were shown to have no amastigotes. The ulcers that did not responded to paromomycin ointment were subsequently treated with PDT

Asilian and Davami developed a placebo-controlled, randomized clinical trial that provided definitive evidence of the efficacy of PDT in the treatment of CL [34]. 60 patients with confirmed CL by clinical and parasitological diagnosis were separated in 3 groups with different treatments. Group 1 was treated with PDT once a week, group 2 received twice daily para‐ momycin plus methylbenzethonium chloride ointment and in group 3 was used a paraffinbased ointment without active ingredients with same application time of the group 2. During four weeks, the groups received the treatments described above. At the end of the study healing was present in 93.5% of the patients of group 1, 41.2% of group 2 and 13.3% of group 3. At the same time, 100%, 64.7% and 20% of the lesions had parasitological cure in group 1, 2 and 3,

Other studies accomplished in Iran and German corroborated with the results described above. According to the authors, PDT showed to have the capacity to treat wounds caused by Old Word *Leishmania* species. We emphasize that most of the reports claim that this therapeutical modality can achieve results above 90% healing of wounds, however, a caveat must be held since some of these studies indicate that not all healed wounds become free of parasite [35,56]. The mechanism of ALA PDT in the case of leishmaniasis was shown to be due to the killing of infected host-cell killing (macrophages) instead of direct parasite killing (see further

One CL case of the New World leishmaniasis is described in the literature. Song *et al.* reported the case of a Brazilian patient presenting cutaneous leishmaniasis confirmed by smear stained by Giemsa. PDT was carried out using MB. In this specific case because of ethical concerns of possible development of evolution to mucocutaneou disease, the patient received at the same time a low dose of pentavalent antimony and PDT. The patient had two ulcers. One receive PDT and the other was only being treated with the low-dose pentavalent [27]. The treatment

**Leishmaniasis**

402 Leishmaniasis - Trends in Epidemiology, Diagnosis and Treatment

successfully.

respectively.

discussion about this issue on section 8).


\* First compound in the porphyrin synthesis pathway, precursor of Protoporphyrin IX (PpIX)

\* First compound in the porphyrin synthesis pathway, precursor of Protoporphyrin IX (PpIX)

TABLE 2: Parameters used in PDT on the treatment of Old World and New World tegumentary leishmaniasis in humans

**Table 2.** Parameters used in PDT on the treatment of Old World and New World tegumentary leishmaniasis in humans

This brief account of the use of PDT for the treatment of CL demonstrates the ability of this therapeutic modality and encourages its use. It also stimulates research in the pur‐ suit of new protocols with new PS, which could ensure not only healing but also clinical and parasitological cure of these patients.

Details of parameters from scientific studies using PDT on the treatment of Old World and New World tegumentary leishmaniasis in humans are described in Table 2.
