Comparison of Intralesional Sodium Stibogluconate versus Intralesional Meglumine Antimoniate for the Treatment of Leishmania major Cutaneous Leishmaniasis.

Israel is endemic for Old-World cutaneous leishmaniasis. The most common species is Leishmania major. However, the available treatment options are limited. This study's objective was to compare the authors' experience with different antimony intralesional treatments of Leishmania major cutaneous leishmaniasis. A retrospective evaluation was undertaken for cases of Leishmania major cutaneous leishmaniasis treated by pentavalent antimony in a university-affiliated medical centre in Israel. The previous treatment of intralesional sodium stibogluconate (Pentostam®) was compared with the current treatment of meglumine antimoniate (Glucantime®). One hundred cases of cutaneous leishmaniasis were treated during the study period, of whom 33 were treated with intralesional sodium stibogluconate and 67 were treated with intralesional meglumine antimoniate. The patients were 78 males and 22 females, mean age 24 (range 10-67) and there was a total of 354 skin lesions. Within 3 months from treatment, 91% (30/33) of the intralesional sodium stibogluconate group and 88% (59/67) of the intralesional meglumine antimoniate group had complete healing of the cutaneous lesions after an average of 3 treatment cycles (non-statistically significant). In conclusion, the 2 different medications have the same efficacy and safety for treating cutaneous leishmaniasis. Pentavalent antimoniate intralesional infiltration treatment is safe, effective, and well tolerated with minimal side effects for Old-World cutaneous leishmaniasis.

Antileishmanial efficacy and tolerability of combined treatment with non-ionic surfactant vesicle formulations of sodium stibogluconate and paromomycin in dogs.

Infection with Leishmania infantum causes the disease visceral leishmaniasis (VL), which is a serious clinical and veterinary problem. The drugs used to treat canine leishmaniasis (CanL) do not cause complete parasite clearance; they can be toxic, and emerging drug resistance in parasite populations limits their clinical utility. Therefore, in this study we have evaluated the toxicity and efficacy of joint treatment with a 1:1 mixture of sodium stibogluconate-NIV (SSG-NIV, 10 mg Sbv/day) and paromomycin-NIV (PMM-NIV, 10 mg PMM/kg/day), given intravenously daily for seven days from day 270 post-infection, to nine-month-old female beagle dogs (n = 6) experimentally infected with Leishmania infantum. Treatment significantly improved the clinical symptoms of VL infection in all the treated dogs, reduced parasite burdens in lymph nodes and bone marrow, and all symptomatic treated dogs, were asymptomatic at 90 days post-treatment. Treatment was associated with a progressive and significant decrease in specific IgG anti-Leishmania antibodies using parasite soluble antigen (p < 0.01) or rK39 (p < 0.01) as the target antigen. In addition, all dogs were classified as parasite negative based on Leishmania nested PCR and quantitative real time PCR tests and as well as an inability to culture of promastigote parasites from lymph nodes and bone marrow tissue samples taken at day 90 post-treatment. However, treatment did not cure the dogs as parasites were detected at 10 months post-treatment, indicating that a different dosing regimen is required to cause long term cure or prevent relapse.

Fractional Ablative CO2 Laser Followed by Topical Application of Sodium Stibogluconate for Treatment of Active Cutaneous Leishmaniasis: A Randomized Controlled Trial.

Conventional treatment of cutaneous leishmaniasis often leaves permanent scars with frequent psychosocial sequelae. The aim of this study was to compare the efficacy, safety, associated pain and final cosmetic outcome of fractional carbon dioxide (CO2) laser followed by topical application of sodium stibogluconate vs. sodium stibogluconate injections for the treatment of cutaneous leishmaniasis. A total of 181 lesions (20 patients) were randomly assigned to receive intralesional injections of sodium stibogluconate (control group) or fractional CO2 laser treatment followed by topical application of sodium stibogluconate (study group). The visual analogue scale (VAS) score of the control group was much higher than that of the study group (6.85 vs. 3.5, respectively, p<0.001). Both the patients and 2 blinded dermatologists found the final cosmetic outcome to be superior for laser-treated lesions (p = 0.001 vs. p =0.008 for controls). Fractional CO2 laser treatment followed by topical application of sodium stibogluconate is less painful and leads to a better final cosmetic outcome compared with intralesional injections of sodium stibogluconate.

Combined chemotherapy manifest less severe immunopathology effects in helminth-protozoa comorbidity.

BACKGROUND: Co-infection with Leishmania major and Schistosoma mansoni may have significant consequences for disease progression, severity and subsequent transmission dynamics. Pentavalent antimonials and Praziquantel (PZQ) are used as first line of treatment for Leishmania and Schistosoma infections respectively. However, there is limited insight on how combined therapy with the standard drugs impacts the host in comorbidity. The study aimed to determine the efficacy of combined chemotherapy using Pentostam (P) and PZQ in murine model co-infected with L. major and S. mansoni. METHODS: A 3 × 4 factorial design with three parasite infection groups (Lm, Sm, Lm + Sm to represent L. major, S. mansoni and L. major + S. mansoni respectively) and four treatment regimens [P, PZQ, P + PZQ, and PBS designating Pentostam (GlaxoSmithKline UK), Praziquantel (Biltricide®, Bayer Ag. Leverkusen, Germany), Pentostam + Praziquantel and Phosphate buffered saline] as factors was applied. RESULTS: Significant changes were observed in the serum Interferon gamma (IFN-γ), and Macrophage inflammatory protein-one alpha (MIP-1α) levels among various treatment groups between week 8 and week 10 (p < 0.05). There was increased IFN-γ in the L. major infected mice subjected to PZQ and PBS, and in L. major + S. mansoni infected BALB/c mice treated with P + PZQ. Subsequently, MIP-1α levels increased significantly in both the L. major infected mice under PZQ and PBS and in L. major + S. mansoni infected BALB/c mice undergoing concurrent chemotherapy with P + PZQ between 8 and 10 weeks (p < 0.05). In the comorbidity, simultaneous chemotherapy resulted in less severe histopathological effects in the liver. CONCLUSION: It was evident, combined first line of treatment is a more effective strategy in managing co-infection of L. major and S. mansoni. The findings denote simultaneous chemotherapy compliments immunomodulation in the helminth-protozoa comorbidity hence, less severe pathological effects following the parasites infection. Recent cases of increased incidences of polyparasitism in vertebrates call for better ways to manage co-infections. The findings presented necessitate intrinsic biological interest on examining optimal combined chemotherapeutic agents strategies in helminth-protozoa concomitance and the related infections abatement trends vis-a-vis host-parasite relationships.

Fractional ablative carbon dioxide laser followed by topical sodium stibogluconate application: A treatment option for pediatric cutaneous leishmaniasis.

BACKGROUND: Leishmaniasis is a protozoan zoonotic parasitic infection with cutaneous, mucocutaneous, and visceral manifestations. Israel is endemic for cutaneous leishmaniasis, which is a self-limited disease but is associated with scarring, which is often a source of psychological and social burden for patients. Scars can be especially devastating for children and teenagers. A wide range of physical and medical approaches is used to treat cutaneous leishmaniasis, among which intralesional injections of sodium stibogluconate rank among the most frequently used. Unfortunately, despite being effective, this therapeutic modality can be very painful. Fractional ablative laser creates a controlled mesh-like pattern of tissue ablation in the skin that promotes dermal remodeling and collagen production while at the same time facilitating enhanced delivery of topically applied medications. METHODS: Patients were treated with fractional ablative carbon dioxide laser followed by immediate topical application of sodium stibogluconate. All children were diagnosed with cutaneous leishmaniasis prior to treatment initiation.. RESULTS: Ten children were treated. One leishmania tropica-positive girl failed to respond. The other nine patients achieved clinical cure and demonstrated good to excellent final cosmesis. Self-rated patient satisfaction and tolerance were high No adverse effects were observed or reported during treatment. CONCLUSION: Fractional ablative carbon dioxide laser followed by topical sodium stibogluconate application appears to be a safe and promising treatment for cutaneous leishmaniasis infection in children. Future controlled studies are required to validate these findings and compare this technique with traditional approaches.

Serological signatures of clinical cure following successful treatment with sodium stibogluconate in Ethiopian visceral leishmaniasis.

BACKGROUND: In Ethiopia, visceral leishmaniasis (VL) is a growing public health threat. Among the key challenges in VL control in Ethiopia is lack of an effective test of cure. The recommended test of cure is parasite detection. As sterile cure is not expected with the current widely used drugs, the value of parasite detection as test of cure is questionable. Moreover, the sampling is invasive, requires a well-equipped facility and highly skilled personnel, which are all hardly found in endemic set-ups. OBJECTIVE: Our aim was to assess the value of sCD40L, MMP9 and IL-10 serum levels as signature biomarkers of clinical cure in VL cases from Ethiopia. METHODS: A total of 45 VL cases before and after treatment and 30 endemic healthy controls were included in the study. Sandwich ELISA was used to measure serum levels of sCD40L, MMP9 and IL-10. RESULT: The mean sCD40L, MMP9 and IL-10 serum levels changed significantly at clinical cure. At individual case level sCD40L and MMP9 showed an increasing trend. Yet, the degree of increase in serum level of MMP9 seems to be affected by nutritional status of the individual VL case. The mean IL-10 serum level was significantly reduced at clinical cure. As seen on case by case basis, all demonstrated a declining trend except that two VL cases had a high IL10 level at clinical cure. CONCLUSION: Our result is suggestive of the possibility of developing a signature biomarker to monitor VL treatment in Ethiopia using one or a combination of parameters.

VISCERAL LEISHMANIASIS FROM AN AREA PREVIOUSLY NOT KNOWN TO BE ENDEMIC; DANGUR, BENSHANGUL-GUMUZ, REGIONAL STATE, NORTHWEST ETHIOPIA: A CASE REPORT.

Visceral leishmaniasis (VL) is a ftial and growing public health problem in Ethiopia. VL is recently reported outside the major endemic foci, the lowlands in the northwest and the Omo and Abaroba-plain, Segen and Woito valleys in the southwest. Here, we report a visceral leishmaniasis case from Benishangul-Gumuz Regional state near the Guba area. The patient had no history of travel to known VL endemic areas. The patient is a temporary farm laborer from West Go'jam Zone, Wanbermna District in Amhara Regional State. While in Benishangul-Gumuz, the patient was diagnosed with prolonged and intermittentfever, epistaxis, splenomegaly, skin pallor, diarrhea, cough and oedema. Laboratory diagnosis results showed that he had marked leucopenia, thrombocytopenia and anemia. The patient was suspected of having VL and checked with rK39 immunochromnatography and direct agglutination tests which were positive for anti leishmanial antibodies. After getting full dose of sodium stibogluconate as per the national visceral leishmaniasis treatment guideline, was clinically cured. As the area in Benshangul-Gumuz where this patient contracted visceral leishmaniasis is under social and ecological transformation with large scale projects attracting huge influx of temporary laborers and settlers, due attention is needed with respect to introduction or emergence of VL transmission.

Leishmania tropica in children: a retrospective study.

BACKGROUND: Limited data are available regarding topical and systemic therapies for Leishmania tropica in children. OBJECTIVE: We sought to characterize the clinical presentation and evaluate the efficacy and safety of topical and systemic treatments in pediatric patients infected with L tropica. METHODS: A retrospective study was performed on 47 children with L tropica cutaneous leishmaniasis. Treatments included topical or systemic therapy with liposomal amphotericin B or pentavalent antimony. RESULTS: Seventy patients with L tropica cutaneous leishmaniasis were treated at our center between 2008 and 2012, of which 47 (67%) were children. The average age of the pediatric population was 8.8 years, and the face was the most common site of involvement (76%). The average number of lesions was 2.6. 24 children (51%) required systemic therapy. The patients were treated with 3 to 5 mg/kg/d of intravenous liposomal amphotericin B, and a response was observed in 83% of the patients within 3 months. LIMITATIONS: This was a retrospective study. CONCLUSION: The disease burden of L tropica in children is high, and because of facial involvement and a low response to topical therapies, systemic therapy is often required. In our experience, liposomal amphotericin B treatment in children is safe and effective and is required for a considerably shorter duration than treatment with pentavalent antimony.

[Cutaneous leishmaniasis. Diagnosis and therapy in northern Afghanistan]. / Erfahrungen mit der kutanen Leishmaniasis. Diagnostik und Therapie im Einsatz in Nordafghanistan.

BACKGROUND: The German S1 guidelines from 2009 contain a variety of recommendations for the treatment of cutaneous leishmaniasis. PATIENTS AND METHODS: We report the results of our diagnostic procedures and treatment of 32 international patients in autumn 2010 in northern Afghanistan. RESULTS: Giemsa stain confirmed the clinical diagnosis within 24 hours. Eleven simple lesions and one larger ulcer responded well to cryotherapy and intralesional sodium stibogluconate. More complex lesions in 19 patients responded well to oral miltefosine. One patient refused outpatient therapy. CONCLUSIONS: Cryotherapy and intralesional antimony compounds showed good results in early lesions of cutaneous leishmaniasis in northern Afghanistan. Outpatient treatment of complex lesions with miltefosine was successful in all cases.

Long-term efficacy of single-dose radiofrequency-induced heat therapy vs. intralesional antimonials for cutaneous leishmaniasis in India.

BACKGROUND: Radiofrequency-induced heat therapy (RFHT) has been found to be safe and effective against cutaneous leishmaniasis (CL) in the short term, but its long-term efficacy is unclear. OBJECTIVES: To compare the long-term efficacy of RFHT vs. intralesional sodium stibogluconate (SSG) injections in the treatment of CL in India. METHODS: One hundred patients with a confirmed diagnosis of CL were randomly assigned in a 1 : 1 ratio to receive topical RFHT for 30-60 s or seven intralesional injections of SSG (50 mg cm(-2) of lesion). Improvement and recurrence were monitored every 15 days after the initiation of treatment for 4 months and then at 5, 6, 9, 12 and 18 months post-treatment; the rates of complete cure were compared. RESULTS: Lesions were healed in 47 out of 50 patients (94%) in the RFHT group and in 46 out of 50 patients (92%) in the SSG group at week 12. Time to complete healing was comparable in the two groups. At 6 months post-treatment, cure rates in the RFHT and SSG groups were 98% [95% confidence interval (CI) 94-100%] and 94% (95% CI 86-100%), respectively. Age, sex and lesion size or number had no effect on cure rates. No relapse of infection was recorded in cured patients in either group up to 12-18 months after initiation of treatment. Skin biopsies of cured lesions in eight out of eight (100%) patients from the RFHT group and three of three from the SSG group at 12 months showed minimal fibrosis and were negative for Leishmania tropica by polymerase chain reaction test. CONCLUSIONS: A single application of RFHT is safe, cosmetically acceptable and effective in inducing a long-term cure of CL.

Liposomal amphotericin B in comparison to sodium stibogluconate for Leishmania braziliensis cutaneous leishmaniasis in travelers.

BACKGROUND: New World cutaneous leishmaniasis is mostly acquired in the Amazon Basin of Bolivia where L viannia (V) braziliensis is endemic. Treatment with systemic pentavalent antimonial compounds has been shown to be effective in achieving clinical cure in only 75% of cases. OBJECTIVE: We sought to assess the efficacy and safety of liposomal amphotericin B (L-AmB) treatment for primary infection of cutaneous L (V) braziliensis. METHODS: A prospective observational evaluation was performed for cutaneous leishmaniasis due to L (V) braziliensis which was treated with L-AmB, 3 mg/kg, for 5 consecutive days, and a sixth dose on day 10. This therapy regimen was compared with the treatment regimen of sodium stibogluconate (SSG) 20 mg/kg for 3 weeks. RESULTS: Our study was divided into two groups; 34 patients received L-AmB and 34 received SSG treatment. Almost all patients were infected in Bolivia. In the L-AmB group, 29 patients (85%) had complete cure compared with 70% in the SSG group (P = not significant), 4 other patients were slow healers, and only one patient needed additional treatment with SSG. No relapses were seen during a mean 29-month follow-up period. Failure rate was 3% in the L-AmB versus 29% in the SSG group (P = .006). Treatment was interrupted in 65% of patients taking SSG because of adverse events, whereas all patients receiving L-AmB completed treatment. LIMITATIONS: This was a non-blinded comparative study. CONCLUSIONS: Comparison of L-Amb to SSG treatment for L (V) braziliensis shows that the former is effective, better tolerated, and more cost effective. L-AmB should therefore be considered as the first-line treatment option for cutaneous L (V) braziliensis infection.

Discovery of safe and orally effective 4-aminoquinaldine analogues as apoptotic inducers with activity against experimental visceral leishmaniasis.

Novel antileishmanials are urgently required to overcome emergence of drug resistance, cytotoxic effects, and difficulties in oral delivery. Toward this, we investigated a series of novel 4-aminoquinaldine derivatives, a new class of molecules, as potential antileishmanials. 4-Aminoquinaldine derivatives presented inhibitory effects on L. donovani promastigotes and amastigotes (50% inhibitory concentration range, 0.94 to 127 µM). Of these, PP-9 and PP-10 were the most effective in vitro and demonstrated strong efficacies in vivo through the intraperitoneal route. They were also found to be effective against both sodium antimony gluconate-sensitive and -resistant Leishmania donovani strains in BALB/c mice when treated orally, resulting in more than 95% protection. Investigation of their mode of action revealed that killing by PP-10 involved moderate inhibition of dihydrofolate reductase and elicitation of the apoptotic cascade. Our studies implicate that PP-10 augments reactive oxygen species generation, evidenced from decreased glutathione levels and increased lipid peroxidation. Subsequent disruption of Leishmania promastigote mitochondrial membrane potential and activation of cytosolic proteases initiated the apoptotic pathway, resulting in DNA fragmentation and parasite death. Our results demonstrate that PP-9 and PP-10 are promising lead compounds with the potential for treating visceral leishmaniasis (VL) through the oral route.

Therapeutic glucocorticoid-induced TNF receptor-mediated amplification of CD4+ T cell responses enhances antiparasitic immunity.

Chronic infectious diseases and cancers are often associated with suboptimal effector T cell responses. Enhancement of T cell costimulatory signals has been extensively studied for cancer immunotherapy but not so for the treatment of infectious disease. The few previous attempts at this strategy using infection models have lacked cellular specificity, with major immunoregulatory mechanisms or innate immune cells also being targeted. In this study, we examined the potential of promoting T cell responses via the glucocorticoid-induced TNF receptor (GITR) family-related protein in a murine model of visceral leishmaniasis. GITR stimulation during established infection markedly improved antiparasitic immunity. This required CD4(+) T cells, TNF, and IFN-gamma, but crucially, was independent of regulatory T (Treg) cells. GITR stimulation enhanced CD4(+) T cell expansion without modulating Treg cell function or protecting conventional CD4(+) T cells from Treg cell suppression. GITR stimulation substantially improved the efficacy of a first-line visceral leishmaniasis drug against both acute hepatic infection and chronic infection in the spleen, demonstrating its potential to improve clinical outcomes. This study identifies a novel strategy to therapeutically enhance CD4(+) T cell-mediated antiparasitic immunity and, importantly, achieves this goal without impairment of Treg cell function.

In vitro and in vivo prophylactic and curative activity of the triterpene saponin PX-6518 against cutaneous Leishmania species.

OBJECTIVES: The oleanane triterpene saponin PX-6518, with known potent in vitro and in vivo activity against Leishmania donovani, was investigated for its spectrum against the cutaneous species Leishmania mexicana, Leishmania panamensis and Leishmania major. METHODS: In vitro activity was based on the reduction of amastigotes in primary peritoneal mouse macrophages. BALB/c mice were injected with 2 × 10(6) amastigotes in the base of the tail (L. panamensis and L. major) or the foot (L. mexicana) and subcutaneously treated with PX-6518 [1-10 mg/kg body weight (BW)] or Pentostam(®) (250 mg/kg BW Sb(V) eq). Evolution of skin lesions was monitored in a prophylactic dose-finding study, and early curative [6 weeks post-infection (pi)] and late curative (>8-10 weeks pi) studies. RESULTS: While moderate susceptibility to PX-6518 was obtained in vitro (IC(50): 1-4 µg/mL), excellent in vivo activity was demonstrated. In the prophylactic study (six administrations on alternate days, starting at 1 day pi), PX-6518 was 100% effective at 1 mg/kg BW against L. mexicana and L. panamensis, whereas L. major lesions could be prevented at 2 mg/kg BW. In the early curative (1 mg/kg BW once a week for 4 weeks) and late curative (1 mg/kg BW twice a week for 4 weeks) studies, PX-6518 completely healed L. mexicana and L. panamensis lesions, whereas L. major lesions were reduced by ∼ 50%. CONCLUSIONS: This study demonstrates that PX-6518 possesses potent and broad-spectrum prophylactic and curative efficacy against cutaneous leishmaniasis in the BALB/c mouse model. L. major was the least susceptible species tested and parasitological cure could not be obtained.

New World cutaneous leishmaniasis: current challenges in diagnosis and parenteral treatment.

Many physicians in the United States and other nonendemic countries lack familiarity with New World cutaneous leishmaniasis (CL) and fail to include it in their differential diagnosis when seeing patients with suggestive lesions and recent high-risk travel. Moreover, even when the diagnosis of New World CL is considered and confirmed, physicians in the United States still face obstacles in obtaining appropriate treatment. In this report, we present 3 cases of New World CL that were either initially misdiagnosed or faced significant delays in therapy. We also discuss the optimal approach by which to confirm New World CL and to collaborate with professional colleagues at the Centers for Disease Control and Prevention in treating individual patients. In particular, when pentavalent antimonial treatment is needed for treatment, physicians must obtain appropriate diagnostic studies, communicate with experts at the Centers for Disease Control and Prevention, complete necessary paperwork, and obtain approval from their local institutional review board to administer it.

Efficacy and safety of a combined treatment of sodium stibogluconate at 20mg/kg/day with upper maximum daily dose limit of 850mg and Paromomycin 15mg/kg/day in HIV negative visceral leishmaniasis patients. A retrospective study, northwest Ethiopia.

BACKGROUND: Visceral leishmaniasis (VL) is one of the most neglected tropical infectious diseases. It is fatal if left untreated. The objective of this study was to assess the efficacy and safety of 17-day injections of combined regimen of sodium stibogluconate and paromomycin (SSG/PM) in HIV-negative VL patients. METHODS: A retrospective analysis of medical records of VL patients treated in the University of Gondar Hospital during period 2012-2019 was carried out. RESULTS: A total of 2836 patients were treated for VL from 2012 to 2019. Of these 1233 were treated with SSG-PM, and 1000 of them were included in the study. Initial cure was achieved in 922 (92.2%) patients. The frequency of treatment failure, treatment interruptions, default and deaths respectively were 30 (3%), 20 (2%), 13 (1.3%) and 15 (1.5%). Among 280 patients who completed 6-month follow up, the final cure was 93.9% (263/280), 4 (1.4%) relapsed and 13 (4.6%) developed post-kala-azar dermal leishmaniasis (PKDL). The most common adverse events (AEs) were raised liver transaminases (35.1%; 351 patients), injection site pain (29.1%, 291 patients) and raised serum alpha-amylase (29.1%, 291 patients). Factors associated with poor treatment outcomes were sepsis, pneumonia, and adverse events. CONCLUSION: A combination of SSG at 20mg/kg with upper daily maximum dose of 850mg and PM was effective for achieving initial cure at end of treatment and safe for treatment of HIV negative VL patients in northwestern Ethiopia. Our data are consistent with previous reports and confirms effectiveness of SSG/PM treatment regimen in the Eastern African countries. Efficacy at 6-months (93.9%) was estimated on data derived from patients who completed follow up and needs to be interrogated by future studies.

Clinical and epidemiological study of cutaneous leishmaniasis in two tertiary care hospitals of Jammu and Kashmir: An emerging disease in North India.

BACKGROUND: An increasing number of patients with cutaneous leishmaniasis (CL) are reporting to tertiary care centers in Jammu and Kashmir, an area that has previously been non-endemic for this disease. This merits consideration of CL as a major health problem of considerable epidemiological importance. The aims of this study were firstly to describe the clinico-epidemiological profile, therapeutic characteristics, and outcomes of patients with CL and secondly to highlight this union territory as a new focus of endemicity for CL. METHODS: A two-center hospital-based prospective cohort study was conducted at two tertiary care hospitals in Jammu and Kashmir over a period of 10 years (July 2009 to June 19). All patients presenting to the outpatient departments with lesions suggestive of CL were enrolled for the purpose of this study. Demographic data were recorded on a proforma questionnaire, along with a detailed history and the results of a meticulous examination. Patients diagnosed with CL based on clinical criteria were subjected to slit skin smear (SSS) and histopathological examination for confirmation of the diagnosis. An intralesional pentavalent antimonial, sodium stibogluconate (SSG), was administered at a dose of 0.5 mL/cm2 (100 mg/mL solution) three times weekly to those patients with smaller lesions, and intravenously or intramuscularly at a dose of 20 mg/kg/day to those with larger lesions. The response to treatment was assessed by total re-epithelialization of the lesion and an absence of infiltration and erythema, with or without scarring. Treatment was given until complete resolution of the lesions or for a maximum duration of 10 weeks when given intralesionally and 3 weeks when given systemically. Clinical follow-up was performed twice weekly for the first 2 months and monthly thereafter. The final response to treatment was assessed at 6 months. RESULTS: The study included a total of 1300 patients with a mean age of 26.7 ± 18.5 years. The mean duration of the disease was 28.52 ± 13.5 weeks, ranging from 8 to 64 weeks. Lesions were noted mainly on exposed parts of the body, with the face being the most commonly affected site (89.00%). Nodulo-ulcerative plaques were the predominant lesion type observed (73.92%). The presence of Leishman-Donovan bodies could be demonstrated on SSS and histopathology in 60.69% and 39.54% of patients, respectively. The presence of a recognizable histological pattern conforming to CL and a response to a therapeutic trial of SSG was considered to be confirmatory in the remaining patients. Complete cure was achieved in 84.23% of cases during the study period. Single lesions were more likely to respond to treatment as compared to multiple lesions. The route of administration did not have any significant impact on the final outcome. CONCLUSIONS: With the disease showing an escalating trend in Jammu and Kashmir, the possibility of a new focus of endemicity and its impact on public health need to be contemplated, and appropriate measures should be initiated to contain its spread.

Evaluation of localized and systemic immune responses in cutaneous leishmaniasis caused by Leishmania tropica: interleukin-8, monocyte chemotactic protein-1 and nitric oxide are major regulatory factors.

We have established Leishmania tropica as the causative agent of cutaneous leishmaniasis (CL) in the region of India where the disease is endemic. The association between localized and circulating levels of immune-determinants in CL patients was evaluated. Reverse transcription-polymerase chain reaction analysis revealed up-regulation of interferon-gamma (IFN-gamma), interleukin (IL)-1beta, IL-8, tumour necrosis factor-alpha (TNF-alpha), IL-10 and IL-4 in dermal lesions at the pretreatment stage (n = 31) compared with healthy controls (P < 0.001) and a significant down-regulation after treatment (n = 14, P < 0.05). The results indicated that an unfavourable clinical outcome in CL was not related to an inadequate T helper 1 (Th1) cell response, but rather to impairment in multiple immune functions. Comparative assessment of treatment regimes with rifampicin (RFM) or sodium antimony gluconate (SAG) revealed tissue cytokine levels to be significantly reduced after treatment with RFM (P < 0.005), while no significant decrease was evident in the levels of IFN-gamma, TNF-alpha and IL-10 (P > 0.05) as a result of treatment with SAG. Increased transcripts of monocyte chemoattractant protein-1 (MCP-1) (P < 0.001) and inducible nitric oxide synthase (iNOS) (P < 0.05) were evident before treatment in tissue lesions and remained high after treatment. Immunohistochemistry demonstrated strong expression of myeloperoxidase (MPO) and IL-8, and moderate expression of iNOS in dermal lesions. The expression levels of IL-8, MCP-1 and nitric oxide (NO) were high in patient sera before treatment, as determined using cytokine bead array and enzyme-linked immunosorbent assay (ELISA). At the post-treatment stage, the serum IL-8 levels had decreased; however, the levels of MCP-1 and NO remained high. These data suggest that IL-8 is an effector immune-determinant in the progression of CL, whereas NO facilitates the parasite killing by macrophages via MCP-1-mediated stimulation.

Efficacy of short-duration (twice weekly) intralesional sodium stibogluconate in treatment of cutaneous Leishmaniasis in India.

BACKGROUND: Cutaneous leishmaniasis (CL) is caused by Leishmania major and L. tropica in the old world. Bikaner, the 'Thar Desert', situated in the north-western corner of India, is an endemic pocket for CL caused by L. tropica. Skin lesions of CL heal slowly, causing disfiguring scars if remaining untreated. Current recommended treatment for CL comprises systemic administration of sodium stibogluconate (SSG) for 2-3 weeks. Five to seven injections of SSG intralesionally have also been found to be effective. OBJECTIVES: To determine the efficacy of a short-duration, twice-weekly intralesional SSG treatment for CL. METHODS: Two hundred and twenty patients with CL having 298 lesions were included in the present study. They were divided into groups A and B (110 patients each). Patients were treated with five to seven intralesional injections of SSG in doses of 50 mg cm(-2) of lesion either once (group A) or twice (group B) weekly. Improvement was recorded at 6, 8, 10, 12, 16, 20 and 24 weeks and the rate of complete cure was compared. RESULTS: Complete cure rate at 6, 8 and 10 weeks was higher (20%, 57% and 73%, respectively) in group B as compared with group A (12%, 36% and 62%, respectively). The differences in cure rates at these time points were statistically significant (P < 0.05). The complete cure rate at 24 weeks was similar in both groups (96% in group B and 92% in group A). The remaining 4% and 8% of patients in groups B and A were 'nonresponders', respectively. No major side-effects were observed in either group. In all cured cases, there were no relapses reported up to 2 years after treatment. CONCLUSIONS: A short-duration, twice-weekly intralesional SSG treatment for CL accelerates cure and is highly effective and well tolerated.