Indigenous leishmaniasis in Taiwan: report of a case

Authors



Yue-Zon Kuan, md Department of Dermatology Chang Gung Memorial Hospital 199, Tun Hwa North Road Taipei Taiwan
E-mail: derma0006@adm.cgmh.org.tw

Abstract

Taiwan is not considered an endemic area of leishmaniasis. Imported cases are encountered infrequently, and only two cases of indigenous cutaneous leishmaniasis have been reported.1 We found one new case in the past 20 years. The patient presented with erythematous plaques on the nasal bridge and right thumb. Skin biopsy specimens from both sites revealed numerous Leishman–Donovan bodies in macrophages. There was no history of travel outside the country, and the diagnosis of indigenous cutaneous leishmaniasis was made. Polymerase chain reactions (PCR) identified the species as Leishmania tropica. The route of infection in this patient is unclear. Because pentavalent antimony, the drug of choice for leishmaniasis, is not available in Taiwan, the patient was treated with levamisole and potassium iodide, with an excellent response.

Introduction

Leishmaniasis is a protozoan disease caused by the parasite Leishmania and transmitted by infected phlebotomine sand flies. The parasite has a digenetic life cycle shuttling between a flagellated promastigote in the gut of a sand fly and an intracellular amastigote in mammalian macrophages, which are the obligate hosts of the parasite. The term leishmaniasis includes cutaneous, mucocutaneous, and visceral types.2

Case Report

In May 2005, a 57-year-old woman presented with a 1-month history of an erythematous plaque on the nasal bridge (Fig. 1), and a 1-week history of a papule involving her right thumb. The lesions were mildly pruritic but not painful. The patient had chronic diabetes mellitus and Graves disease. She has worked as a fruit farmer on Mount Takuan in northern Taiwan, but she had not contacted exotic fruit or traveled outside the country. There was no history of trauma or insect bite. She had an apparently healthy dog and previously had a dog that died from an unknown disease.

Figure 1.

A poorly demarcated, indurated erythematous plaque involving the nasal bridge

The skin lesions measured 1.2 cm and 0.5 cm in diameter, respectively. There was no nasal deformity, lymphadenopathy, or hepatosplenomegaly. Biopsy was obtained from the nasal bridge lesion, and the papule of the right thumb was excised completely. Histologic examination of both lesions revealed multiple small granulomas on a background of heavy lymphoplasmacytic dermal infiltrates (Fig. 2a). There were numerous small organisms in histiocytes, compatible with Leishman–Donovan bodies on Giemsa-stained sections (Fig. 2b). Because the history was negative for travel outside the country, a diagnosis of indigenous cutaneous leishmaniasis was made.

Figure 2.

(a) Multiple small granulomas embedded in a dense lymphoplasmacytic infiltrate, and numerous small cellular organisms within histiocytes (hematoxylin and eosin, ×100). (b) Giemsa-stained section demonstrates the intracellular organisms consistent with Leishman-Donovan bodies (×400)

Western blot analysis, using the patient's serum as an immuno-probe, showed strong reactivity to Leishmania tropica (BTO11) and Leishmania infantum (Bman), but not to Leishmania donovani (Jeddah) and Leishmania major (LH32) (Fig. 3). Total DNA was extracted from a fresh nasal skin biopsy specimen. PCR primers [5′ LITSR (5′-CTGGATCATTTTCCGATG-3′) and 3′ L5.8S (5′-TGATACCACTTATCGCACTT-3′)] were designed to amplify a 300–350-bp region in the ribosomal internal transcribed spacer 1 (ITS1) flanking between the genes coding for SSU and 5.8S rRNA gene. Amplification reactions were performed in 50 µL containing the following: 1.5 mm MgCl2; 200 µm each of dNTPs; 500 nm primers; and 2 units of Taq DNA polymerase. Amplification was performed by a GenAmp PCR System 9700 (Applied Biosystems) with an initial step of denaturation for 3 min at 96 °C, followed by 35 cycles, with each cycle consisting of 30 s at 94 °C, 1 min at 53 °C, and 2 min at 72 °C, and finally, a final extension for 5 min at 72 °C. PCR products were analyzed by DNA gel electrophoresis on a 2% (wt/vol) agarose gel, stained with ethidium bromide, and visualized on a UV transilluminator (Fig. 4). The sequencing result was comparable with the ITS1 region of L. tropica deposited in GenBank (accession no. AJ000301 to AJ000302).

Figure 3.

Western blot result. Serum of the patient showed no reactivity to L. amazonensis (Promastigote) (1), L. amazonensis (Amastigote) (2), L. major (3) and L. donovani (4) while strong reactivity to L. tropica (5) and L. infantum (6)

Figure 4.

Leishmania PCR result. 1: DNA extracted from skin lesion of patient, 2: DNA extracted from normal human skin, 3: negative control

Ketoconazole 400 mg daily for 8 weeks was prescribed because pentavalent antimony, the drug of choice for leishmaniasis, was not available in Taiwan. After a poor clinical response to ketoconazole, subtotal excision of the nasal lesion was performed, and systemic fluconazole 150 mg daily for 8 weeks was prescribed. However, the nasal lesion enlarged. Levamisole hydrochloride 50 mg t.i.d. for 3 days every 2 weeks and potassium iodide 300 mg orally t.i.d. were then prescribed. In 1 month, the lesion appeared smaller, softer, and less erythematous.

Discussion

In 1903, Leishman and Donovan, working separately, described the protozoan Leishmania. Leishmaniasis is a collective term used to describe the diseases caused by 20 Leishmania species pathogenic to mammals. Worldwide, approximately 12 million people have leishmaniasis, with 1.5–2 million new cases reported each year.3 Leishmaniasis is widespread in 22 countries in the New World and in 66 countries in the Old World. The disease is not found in Southeast Asia, except in Vietnam; kala-azar was diagnosed in three HIV-positive women in Vietnam in 2002.4 Leishmaniasis is transmitted by the female phlebotomine sand fly. Thirty out of 500 phlebotomine species have been identified as vectors of the disease.

Leishmaniasis is an important infectious disease in mainland China, especially the regions north of the Yangtze River, such as Xinjiang, Sichuan, Gansu, Shanxi, Shaanxi, Neimenggu, and Shandong.5 Taiwan is not considered to be an endemic area, and leishmaniasis was not seen in Taiwan prior to World War II. About 100 imported cases of kala-azar were observed in civilians and military personnel from mainland China during and after the civil war. The first report of autochthonous leishmaniasis in Taiwan was published in 1985 by John and colleagues.1 They described two native born aboriginal Taiwanese, with cutaneous leishmaniasis, who were from the same village in Hsinchu County of northern Taiwan and had never traveled far from home.1 Although a human-bite sand fly species Phlebotomus kiangsuensis had been identified in Taiwan in 1970,6 John and colleagues could identify only the sand fly Phlebotomus iyengari taiwanensis that feeds on animals in the area. No disease was found in other humans, dogs, cats, rodents, birds, reptiles, and amphibians in the region.

The infectious route in our patient was not clear. Since the possible species was L. tropica, the source of infection probably did not come from mainland China where kala-azar and post-kala-azar dermal leishmaniasis are caused most commonly by L. donovani.1 Because sand flies have been found in Taiwan, physical transmission by sand flies was possible, with village animals as a reservoir, although serum from the patient's dog was negative for leishmania. There probably are unrecognized autochthonous foci, such as wild animals, in the remote mountains of Taiwan.

Treatment of leishmaniasis varies according to the infecting species and clinical severity (Table 1). Lesions of Old World cutaneous leishmaniasis may resolve spontaneously. Intervention is necessary only in the following conditions: cosmetically unacceptable lesions, chronic and large lesions, mucosal disease, multiple lesions, worsening lesions, and lesions in immunosuppressed patients.3 Levamisole and potassium iodide were beneficial in our patient. Levamisole is a levo-isomer of tetramisole, a potent antihelmintic agent. In 1971, its immunomodulatory effects were documented.7 Levamisole is capable of inducing T-cell differentiation and restoring depressed effector function of peripheral lymphocytes and phagocytes. Potassium iodide is used to treat inflammatory dermatoses such as Sweet's syndrome, erythema nodosum, subacute nodular migratory panniculitis, and some cutaneous infection,9 but its mechanism of action is unknown. These drugs also may be useful in other countries where pentavalent antimony is unavailable. More data are needed to establish the roles of levamisole and potassium iodide in the treatment of leishmaniasis.

Table 1.  Treatment of leishmaniasis
 CategoryType of treatmentSpeciesOld WorldNew World
Local treatmentPhysicalCryotherapy11L. tropica L. brasiliensis
L. ethiopica 
Local heat12  
Surgery  
OintmentParomomycinL. major13L. mexicana14
Paromomycin with methylbenzethonium L. panamensis15
Imiquimod16  
Local infiltrationPentavalent antimonyL. major17L. mexicana
L. tropica18 
Photodynamic therapy L. donovani19 
Systemic treatmentIntravenousPentavalent antimony (Sodium stibogluconate)L. major L. guyanensis
L. tropica L. panamensis
L. donovaniL. brasiliensis
Pentamidine L. guyanensis20
Amphotericin B1  
OralKetoconazoleL. major21L. Mexicana22
 L. panamensis23
FluconazoleL. major24 (no response to L. tropica25) 
Other: Rifampin26; Dapsone1; Allopurinol1; Pentoxifiline27; Miltefosine28  
ImmunotherapyVaccination29  
Interferone-γ30  
OtherSitamaquine (WR6026)31  
Phytotherapy32  

Ancillary