Iceberg phenomenon in cutaneous leishmaniasis: A sporotrichoid clue.

Interventions for American cutaneous and mucocutaneous leishmaniasis.

Multiple ulcerated lesions in a patient from Amazon, Brazil

Leishmaniasis is currently considered a re-emerging or emerging infection based on the geographic region. The outcome of leishmaniasis vastly depends on Leishmania-host interaction. This preliminary study aimed to show the association of human leukocyte antigen (HLA) class I and II genes with healed and non-healed cutaneous leishmaniasis (CL), and symptomatic and asymptomatic visceral leishmaniasis (VL) compared with control groups in Iran. Ninety-five people, including 31 patients versus 64 individuals in the control group, were enrolled. Among them, 20 patients had confirmed CL based on amastigote observation, 10 had improved CL and 10 non-healed CL. Eleven patients were suffering from confirmed VL based on direct agglutination test (Five asymptomatic and six symptomatic VL cases). Besides, they were residents in an endemic area of VL in the northwest of Iran. To select a control group, it was ensured that they had no history of leishmaniasis. Peripheral blood samples were collected from each patient. After DNA extraction, HLA typing was conducted using polymerase chain reaction - sequence-specific priming (PCR-SSP). Subsequently, data were statistically analyzed by SPSS. There was a statistical relationship between the presence of HLA-A26 and CL, healed CL and the existence of the B38 allele, C1 allele and symptomatic VL, as well as B1.4 allele and asymptomatic VL (P<0.05). This primary finding indicates that several HLA genes have a potential role in the susceptibility of Iranian people to CL and VL.

Dear Editor, Literature data on the use of fluconazole in cutaneous leishmaniasis (CL) by Leishmania braziliensis are poor and conflicting.1-4 We present four patients with severe CL by L. braziliensis who were successfully treated with fluconazole (Supplementary Table 1). The patients were four Caucasians who acquired CL after trips to Brazil, Bolivia, and Colombia. All patients were previously, but unsuccessfully, treated with different drugs. All patients were subjected to general and dermatologic examination, laboratory tests, cytologic, and histopathologic examinations, culture in Novy-MacNeal-Nicolle medium and polymerase chain reaction (PCR). In all patients CL was characterized by ulcerative lesions (Figure 1A). Laboratory tests were within normal ranges. Cytologic and histopathologic examinations revealed the presence of Leishmania spp. Culture was positive for Leishmania spp. PCR was positive for L. braziliensis. Leishmanin Skin/Montenegro test was carried out in three patients, who resulted to be positive. Fluconazole was used at the dosage of 400 mg/day for 6–11 months. All patients were examined every month. Laboratory examinations were performed every 2 months. The first clinical improvement was observed 4–6 weeks after the beginning of the therapy. In all patients, complete remission was obtained (Figure 1A–F). Follow-up (≤7 years and 11 months) was negative in all patients. Side effects were local itching, weakness, arthralgia, myalgia and gastralgia (one patient), and local pain and weakness (one patient). In one patient mild increase in azotaemia was detected. In all patients it was unnecessary to stop the therapy. Azole and triazole drugs inhibit the growth of Leishmania spp. by inhibiting the cytochrome P-450–mediated 14α-demethylation of lanosterol, blocking ergosterol synthesis, and causing accumulation of 14α-methyl sterols.5 A recent study demonstrated that L. braziliensis is sensitive in vitro to fluconazole.6 The first report on the use of fluconazole in CL by L. braziliensis was published in 2007: no clinical results were observed in three Austrian soldiers who acquired the infection in Belize.1 Sousa et al.2 successfully used fluconazole in 28 patients. They started with a dosage of 5 mg−1kg−1day−1 and reached 8 mg−1kg−1day−1. The duration of the therapy was 4–12 weeks. With the low dosage, 75% patients recovered; with 8 mg−1kg−1day−1, the cure rate was 100%. The drug was well tolerated. A randomized, controlled study was carried out to compare the efficacy and safety of fluconazole (6.5–8 mg−1kg−1day−1 for 28 days) versus pentavalent antimony (20 mg−1kg−1day−1 for 20 days). A total of 53 patients were included: 27 patients were treated with fluconazole and 26 with antimony. Initial cure rates (two months after treatment) were of 22.2% (6/27 patients) in the fluconazole group and 53.8% (14/26 patients) in the antimony group. No relapses were observed. The frequency of adverse events in the antimony and fluconazole groups was similar: 34.6% versus 37%, respectively. In the group of patients treated with fluconazole, dizziness was observed in 22.2% of them, nausea in 11.1% and headache in 7.4%. One patient discontinued the treatment because of headache and dizziness. According to this study, fluconazole was not considered as an effective therapy.4 Our experience on the use of fluconazole in CL is based on approximately 30 patients: we successfully treated patients with CL by L. panamensis7 and L. infantum.8, 9 Fluconazole was also successfully used in pediatric patients with CL caused by L. major and L. tropica. Furthermore, no important side effects were observed.10, 11 It is possible that the duration of the therapy is important. As previously mentioned, we used fluconazole for 6–11 months: in the first 4–6 weeks of therapy clinical results were slow and partial. In the previously cited study,4 fluconazole was used for only 28 days. We also observed that a long therapy induced neither important side effects nor laboratory abnormalities. In spite of the small number of patients treated, we think that fluconazole can be taken into consideration in patients with CL by L. braziliensis in those countries where pentavalent antimony is no more marketed. The authors declare no potential conflict of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. Supplementary Table 1 Patients' characteristics. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is characterized by a single ulcer or multiple cutaneous lesions with raised borders. Cure rates <60% are observed in response to meglumine antimoniate therapy. We investigated the impact of obesity on CL clinical presentation and therapeutic response. A total of 90 age-matched patients with CL were included (30 obese, 30 overweight, and 30 with normal body mass index [BMI]). CL was diagnosed through documentation of L. braziliensis DNA by polymerase chain reaction or identification of amastigotes in biopsied skin-lesion samples. Serum cytokine levels were determined by chemiluminescence. Antimony therapy with Glucantime (Sanofi-Aventis; 20 mg/kg/day) was administered for 20 days. Obese CL patients may present hypertrophic ulcers rather than typical oval, ulcerated lesions. A direct correlation between BMI and healing time was noted. After 1 course of antimony, cure was achieved in 73% of patients with normal BMI, 37% of overweight subjects, yet just 18% of obese CL patients (P < .01). Obese CL cases additionally presented higher leptin levels than overweight patients or those with normal BMI (P < .05). Obesity modifies the clinical presentation of CL and host immune response and is associated with greater failure to therapy.

Cutaneous Leishmaniasis (CL) is a skin infection caused by various species of Leishmania parasites, which is transmitted by infected Phlebotomus sandfly bites. Pentavalent antimonials (meglumine antimoniate and sodium stibogluconate) are used for the treatment of adult CL patients as an effective and safe method. Liposomal amphotericin B is an alternative for the treatment of choice in cutaneous leishmaniasis cases which pentavalan antimony contraindicated or unresponsive to pentavalent antimony therapy. In this study, successful treatment with systemic liposomal amphotericin B of a cutaneous leishmaniasis case developing local side effects related both systemic and intralesional meglumine antimonate treatment was presented.

A Seven-Month-Old Infant With Acute Onset of Neurologic Deterioration

Localized cutaneous leishmaniasis (CL) typically presents as papules, crusted nodules, plaques, or noduloulcerative lesions. Atypical CL does not show these features or mimic malignant lesion. In atypical forms, CL may be overlooked because of its similarity to other dermal diseases. To compare conventional, molecular, and immunohistochemical methods in the diagnosis of typical and atypical CL. The kinetoplast DNA, nested, polymerase chain reaction assay and immunohistochemical methods were compared and validated against conventional methods, including cytology and pathology, using 100 specimens of typical and atypical lesions of suspected CL. Compared with other methods, polymerase chain reaction of the kinetoplast DNA showed the highest sensitivity (typical positive, 100%, 67 of 67; atypical positive, 94%, 31 of 33) and specificity (100%), followed by immunohistochemistry (typical positive, 97%, 65 of 67, with 100% specificity; atypical positives, 94%, 31 of 33, with 100% specificity), and cytology (typical positive, 79%, 53 of 67, with 100% specificity; atypical positive, 58%, 19 of 33, with 100% specificity), followed by pathology (typical positive, 70%, 47 of 67, with 100% specificity; atypical positive, 42%, 14 of 33, with 100% specificity). In addition, polymerase chain reaction enabled identification of 98% (98 of 100) of the positive samples that included strains of Leishmania major (99% [99 of 100] cases) and Leishmania tropica (1% [1 of 100] cases). Because cytology is cheap and easy to perform with high sensitivity, it is the preferred, primary approach for typical CL, but cytology and pathology do not have sufficient sensitivity for diagnosis of atypical CL cases. Nested polymerase chain reaction and immunohistochemistry are sensitive tests for diagnosis of both typical and atypical CL and are recommended as complementary tests in suspected CL with negative conventional microscopy results.

&#x0D; &#x0D; Background&#x0D; Cutaneous leishmaniasis (CL) remains a serious public health concern in some parts of Iraq. The aims of this study to report of CL in some parts of Iraq, by different parasitological, cultural, and molecular methods and evaluate sex differences among infected patients. This is the first study conducted to characterize Leishmania species causing CL among Iraqi patients using the sequence analysis of Internal Transcribed Spacer1(ITS1) at Wasit Province.&#x0D; Methods&#x0D; A total of 700 cases of suspected CL were referred to the Iraqi clinics and health centres and they checked for Leishmania amastigote using a Giemsa-stain; however, the Novy Macneal Nicolle (NNN) culture led to the growth of promastigotes in all samples, then the samples were examined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP)-PCR methods.&#x0D; Results&#x0D; The present study indicated that the prevalence of CL as follow: AL-Diwaniyah 88(15.1%), Wasit 85 (14.5%), Najaf 79 (13.6%), Thi-Qar76 (13.1%), Basrah 67 (11.5%), Baghdad 65 (11.2%), Diyala 63(10.8%), and Salah-Edin province which recorded lower infection 60 (10.3%), and it appeared in 83.3% by using Giemsa- smeared stain. The highest infection rate (100%) appeared using PCR while the lowest infection (68%) appeared by culture on NNN media. The present study was revealed that the highest infection (60%) was caused by L.major rather than L.tropica (40%). Our results showed that 368 (52.6%) of CL patients were had single lesion and 215 (30.7%) had multiple lesions, and the ulcerative wet type lesions were present in 49.6%, while the nodule dry type lesions were present in 33.7%. The overall prevalence of cutaneous leishmaniasis in the study area was very high (83.3%) having a statistically significant association with sex; males are more prone (56.4%) to CL as compared to females (43.6%)&#x0D; &#x0D; Conclusions&#x0D; A clear and reliable bias toward males exists in some tropical diseases, such as leishmaniasis. CL is a major health problem in Iraq and CL caused by many countries including Iraq. Health authorities should be aware of the fact that war and terrorist activities induce expansion of the disease and increase the incidence rate in the situation that access to medical treatment is not easy especially in poor conditions in leishmaniasis endemic areas.&#x0D; &#x0D; &#x0D;

Autochthonous<i>Leishmania siamensis</i>in Horse, Florida, USA

Leishmaniasis is a common parasitic disease seen in many parts of the world, especially in areas where current U.S. and international forces are deployed. Approximately 350 million people are thought to be at risk of cutaneous leishmaniasis (CL) with an annual incidence of 1.5 million cases. Over 90% of cutaneous infections with Leishmania occur in the Middle East, Brazil, and Peru. Outbreaks of CL may occur in military personnel deployed to endemic areas. Since the incubation period for symptomatic CL ranges from weeks to months, symptoms may not appear until well after returning to the United States. As operations continue to expand globally, the exposure and concern for leishmaniasis persists for military physicians. We describe localized CL in a previously healthy male in an effort to help medical personnel identify leishmaniasis on the basis of cutaneous lesions alone, as well as increase diagnostic suspicion when treating patients in nonendemic areas. A previously healthy 30-year-old Saudi Arabian male presented to the emergency department with a 1-month history of four well-demarcated nonhealing, painless ulcers on his left ear, hand, and foot. Symptoms began shortly after arriving in the United States. He had been treated with trimethoprim/sulfamethoxazole, oral clindamycin, mupirocin ointment, and vancomycin for suspected infection without improvement of lesions. Upon presentation to dermatology, physical examination revealed a firm erythematous plaque with central ulceration on his left ear. Two shallow indurated ulcers were also found on his left fourth dorsal finger and left dorsal foot. Biopsy of the foot revealed granulomatous inflammation with predominantly lymphoplasmacytic infiltrate and multinucleated giant cells. Parasitized histiocytes were identified on hematoxylin and eosin stain and focally on Giemsa stain. Polymerase chain was consistent with a diagnosis of leishmaniasis and outpatient treatment was initiated with fluconazole 200 mg daily for 6 weeks. At 2-week follow-up, lesions were noted to be stabilized. CL has a wide variety of presentations. The classic lesion appears as a papule that will enlarge, often developing into a nodule or plaque-like lesion with central ulceration. The lesion may be covered with an eschar or by fibrinous material. This presentation can mimic many disease processes resulting in an extensive differential diagnosis that includes bacterial, fungal, and viral infections, cutaneous malignancy, and insect bites. The clinical course, treatment options, response to therapy, and prognosis are all highly variable and dependent on the causative species. Local therapy options, oral systemic agents, and parenteral agents have all shown varying results in the treatment of leishmaniasis. The difficulty with standardizing treatment options for CL stems from the lack of well-controlled studies and the lack of standardized outcome measures. This deficiency in comparative studies of treatment hinders consensual recommendations. However, the choice of the correct therapy often depends on the experience of the clinician, burden of disease, preferences of patients, and cost-effectiveness considerations for the patient and/or the health care system.

Background: A combination treatment of cutaneous leishmaniasis (CL) that hastens the healing and reduces the chance of scarring, especially in aesthetically receptive sites, is required.Objectives: To evaluate if a combination of intralesional sodium stibogluconate (SSG) injection and topical imiquimod 5% cream (IMI) accelerates healing and improves the quality of scars from CL.Patients and Methods: A prospective, placebo-controlled, randomized clinical trial was conducted at Basrah Teaching Hospital, Basrah, southern Iraq from 2017 to 2019 on a cohort of patients with CL. Eligible patients were injected intralesionally with sodium stibogluconate (SSG) weekly for six weeks and randomized to receive either topical imiquimod 5% cream (IMI group) or topical emollient cream (placebo group). The healing rate and scar quality were assessed at week six.Results: One hundred twenty-one patients completed the trial (66 [55%] males, mean age SD: 34.1 years). The clinical healing rate was significantly higher in the IMI group than in the placebo group (94% versus 74%, p <0.05). A high rate of scars was noticed in both groups (66.6% in the IMI group and 91.2% in the placebo group). However, superficial non-atrophic scars were more frequent in the IMI group (40% versus 26%), while deep atrophic scars were more evident in the placebo group than in the IMI group (65.2% versus 26.6%, p<0.05).Conclusions: Combined intralesional SSG plus topical imiquimod was beneficial in accelerating CL healing and improving scar quality, and should be considered when CL is located in aesthetically sensitive areas.

Visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) are seen endemically in Turkey and CL caused by Leishmania tropica is an important public health problem in southeastern as well as other regions of Turkey. The diagnosis has been usually made by clinical view of lesion and/or parasitologically using lesion aspiration smears. Histological examination does not, always reveal the parasite in the skin biopsy, particularly in chronic lesions. Besides this, due to CL infections caused by different species in endemic areas, diagnostic methods enabling species identification are in great need. Species identification, in the time of diagnosis, is an important procedure for helping the clinicians in the planning of treatment as well as control measures. Polymerase chain reaction (PCR) is a specific and sensitive diagnostic tool that can also identify the parasite at species level. Kinetoplast DNA (kDNA) is one of the genetic regions that can be used for the detection of Leishmania parasites in clinical specimens, kDNA PCR is reported as one of the most sensitive methods related to species-specific variable regions in mini-circle long time ago. It has been considered as one of the most ideal targets for the diagnosis of leishmaniasis. The aim of the study was to perform PCR targeting kDNA by using the primers of Uni21/Lmj4 in clinical samples and compare the results with other parasitological methods like smear and culture, for the diagnosis of CL. The kDNA PCR, parasite culture and microscopical evaluation of stained smears of 62 specimens from suspected CL cases who have referred to Cutaneous Leishmaniasis Diagnosis and Treatment Center in Sanliurfa, Turkey were included in the study. The kDNA PCR showed the highest sensitivity 100% of the samples (35/35) among all diagnostic assays, followed by the microscopy (25/35 positive, 71.4% sensitivity) and culture (19/35 positive, 54.3% sensitivity). The sensitivity of combination of culture and microscopy was 88.6% (31/35 positive). These results suggested that performing kDNA PCR in addition to conventional techniques is important for improving the true diagnosis of CL to the species level and also important for establishing treatment regimens and designing appropriate precautions in highly endemic area like the southeastern region of Turkey.

Cutaneous leishmaniasis (CL) is a neglected tropical disease with diverse clinical manifestations, ranging from localized CL to severe forms such as diffuse CL and mucocutaneous leishmaniasis. Borderline disseminated CL (BDCL), an intermediate form, is characterized by multiple disseminated lesions and poses unique diagnostic and therapeutic challenges, especially in pediatric patients. This study explores pediatric BDCL to better understand its clinical presentation, diagnostic approaches and treatment outcomes. We report 4 pediatric cases of BDCL from Panama, identified through polymerase chain reaction and histopathological analysis. Species identification utilized polymerase chain reaction and heat shock protein 70 gene sequencing. Treatment included amphotericin B, meglumine antimoniate and miltefosine, with follow-up evaluations assessing lesion progression and treatment outcomes. All patients exhibited multiple disseminated ulcerative and nodular lesions, with some involving mucosal sites. Species identification confirmed Leishmania guyanensis and Leishmania panamensis as causative agents. Two patients received meglumine antimoniate, achieving complete lesion resolution. Due to better tolerability, miltefosine was used in the remaining 2 patients, resulting in slower but complete lesion resolution over time. Amphotericin B demonstrated limited efficacy. Pediatric BDCL presents significant diagnostic and therapeutic challenges due to variable immune responses, clinical presentations and species-related treatment resistance. While meglumine antimoniate and miltefosine showed promising results, amphotericin B was less effective. Further research is needed to establish optimized treatment protocols for pediatric BDCL, considering species-specific responses and pharmacokinetic and pharmacodynamic differences in children.

Cutaneous leishmaniasis (CL) is a parasitic cutaneous infection caused by Leishmania parasite. The histopathology is usually granulomatous in nature. The aim of the present study is to elucidate the histology of CL and evaluate the presence and the frequency of panniculitis among the affected patients. Case series interventional study. Thirty-five patients with CL were diagnosed clinically between December-2012 and May-2013. Diagnostic confirmation established by smears, culture, and polymerase chain reaction (PCR). The histopathological assessment was carried out to study the general pathology and to look for the presence of panniculitis. Simple statistics utilized via SPSS version 16.0 (SPSS, Inc., Chicago, USA). Eighteen women and 17 men with CL were enrolled in the present work with a mean duration of their disease was 3 months. The results of the diagnostic tests were as follow: The smear was positive in 21 (60%) of cases, Leishman-Donovan (LD) bodies were seen in 7 (20%) patients, culture was positive in 24 (68%), and PCR was positive in 32 (91.4%) patients. The epidermal changes included acanthosis, pseudoepitheliomatous hyperplasia, ulceration, focal spongiosis, and interface dermatitis while the dermal changes were dependent on the spectrum of the disease, so in the ulcerative lesions there was lymphohistiocytic infiltration with foci of plasma cells and sometimes aggregate of LD bodies, whereas in the dry lesions the pathology is mainly of epithelioid granuloma. Panniculitis was seen in 16 (46%) cases as a diffuse lymphohistiocytic infiltration of both the septum and lobules of the subcutaneous layer of the skin. Panniculitis is an important feature of CL that must be differentiated from other diseases that can simulate CL such as chronic skin infections, Discoid lupus erythematosus, and cutaneous lymphoma.