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Tidsskrift For Den Norske Laegeforening... Feb 2021Leishmaniasis is a rare but potentially severe tropical infectious disease, and Norwegian clinicians are generally unfamiliar with its diagnosis and treatment. This...
BACKGROUND
Leishmaniasis is a rare but potentially severe tropical infectious disease, and Norwegian clinicians are generally unfamiliar with its diagnosis and treatment. This study aimed to investigate the number of cases diagnosed, performance of diagnostic methods and treatment of leishmaniasis at five university hospitals in Norway.
MATERIAL AND METHOD
The number of cases, diagnosis and treatment of suspected leishmaniasis were registered prospectively in the period March 2014 - September 2017 at the university hospitals of Bergen, Oslo, Stavanger, Trondheim and Tromsø.
RESULTS
A total of 13 patients with leishmaniasis were registered in the period. Visceral leishmaniasis was diagnosed in two patients infected in the Mediterranean region, after 7 and 8 weeks with symptoms. The diagnosis was made by serology as well as microscopy and/or polymerase chain reaction tests (PCR) on spleen, blood and bone marrow. Both patients were treated effectively with liposomal amphotericin B. Cutaneous leishmaniasis was diagnosed in 11 patients, and samples from 10 of these tested positive with PCR. Two patients were infected with potentially mucotropic species. Liposomal amphotericin B was the first-line choice for all those who received treatment, but one patient recovered only after local therapy with sodium stibogluconate.
INTERPRETATION
Assessment of visceral leishmaniasis was undertaken according to international guidelines. The patients were diagnosed late in the disease course, presumably because the disease is rare and not well known in Norway. Cutaneous leishmaniasis was diagnosed with PCR, but none of the patients received local treatment as the first-line choice, as recommended in suitable cases, presumably because the drugs are not readily available in Norway and many clinicians are unfamiliar with the route of administration with local infiltration.
Topics: Antiprotozoal Agents; Bone Marrow; Humans; Leishmaniasis, Visceral; Mediterranean Region; Norway
PubMed: 33624958
DOI: 10.4045/tidsskr.19.0171 -
Journal of Clinical Laboratory Analysis Aug 2022Pentavalent antimonials (Sb(V)) such as meglumine antimoniate (Glucantime®) and sodium stibogluconate (Pentostam®) are used as first-line treatments for leishmaniasis,... (Review)
Review
BACKGROUND
Pentavalent antimonials (Sb(V)) such as meglumine antimoniate (Glucantime®) and sodium stibogluconate (Pentostam®) are used as first-line treatments for leishmaniasis, either alone or in combination with second-line drugs such as amphotericin B (Amp B), miltefosine (MIL), methotrexate (MTX), or cryotherapy. Therapeutic aspects of these drugs are now challenged because of clinical resistance worldwide.
METHODS
We reviewedthe recent original studies were assessed by searching in electronic databases such as Scopus, Pubmed, Embase, and Web of Science.
RESULTS
Studies on molecular biomarkers involved in drug resistance are essential for monitoring the disease. We reviewed genes and mechanisms of resistance to leishmaniasis, and the geographical distribution of these biomarkers in each country has also been thoroughly investigated.
CONCLUSION
Due to the emergence of resistant genes mainly in anthroponotic Leishmania species such as L. donovani and L. tropica, as the causative agents of ACL and AVL, respectively, selection of an appropriate treatment modality is essential. Physicians should be aware of the presence of such resistance for the selection of proper treatment modalities in endemic countries.
Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Biomarkers; Drug Resistance; Humans; Leishmaniasis; Leishmaniasis, Cutaneous; Meglumine Antimoniate
PubMed: 35808933
DOI: 10.1002/jcla.24599 -
Brazilian Journal of Biology = Revista... 2022Current cross-sectional study was carried out between September 2019 to January 2020 at the Department of Pathology, Mardan Medical Complex (MMC), Mardan, and District...
Current cross-sectional study was carried out between September 2019 to January 2020 at the Department of Pathology, Mardan Medical Complex (MMC), Mardan, and District Headquarter Hospital North Waziristan, Khyber Pakhtunkhwa (KP), Pakistan. The objectives of the current study were to determine the prevalence of leishmaniasis and its associated risk factors in selected districts of KP province, Pakistan. Altogether, three hundred and seventy-four (n=374) leishmaniosis patients were included in the current study. Skin specimen from the ulcer border were collected. The slides were stained by Giemsa stain and examined for the presence of amastigote. The prevalence of leishmania infected patients in different region of KP were as follows: North Waziristan region 53.7 (n=201) District Mardan 34.7% (n=130); District Nowshera 6.7% (n=25), District Swabi 1.1% (n=4) and other Districts i.e. Dir, Malakand, Buner and Bajawarr were 3.7% (n=14). The frequency of leishmaniasis were more in male and majority of the infected patients were in the age group of <10 years. Among n=374 patients 95.7% (n= 358) had cutaneous leishmaniasis while 3% (n= 11) had mucocutaneous type of infection and 1.3% (n= 5) patients had both cutaneous and mucocutaneous infection. Upon treatment by Sodium stibogluconate (SSG) 97% (n=362) showed clinical signs of complete or partial recovery of their skin lesions. Conclusively, highest incidence of leishmania infection occurred during short study period and majority of the cases showed positive response to treatment.
Topics: Child; Cross-Sectional Studies; Female; Humans; Leishmaniasis, Cutaneous; Male; Pakistan; Prevalence; Risk Factors
PubMed: 35946727
DOI: 10.1590/1519-6984.249124 -
Journal of Ayub Medical College,... 2020Leishmaniasis is an endemic disease and a major public health problem throughout the world. Its geographic distribution has been extended over the past few years in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Leishmaniasis is an endemic disease and a major public health problem throughout the world. Its geographic distribution has been extended over the past few years in Pakistan. The available treatment options of Leishmaniasis are limited and mostly parenteral, and hence a nontoxic oral alternative therapy is urgently needed to overcome the problem. The objective of this study was to evaluate the synergistic effect of Allopurinol as an adjunct therapy along with conventional intra-lesional sodium Stibogluconate in the treatment of cutaneous Leishmaniasis.
METHODS
This single blinded randomized controlled trial was carried out at the tertiary care hospitals of district Peshawar, Pakistan. A total of one hundred and sixty-four (164) patients of age range from 19-56 years, consisting of both genders were included in this study. All subjects were randomly allocated to Group-1 and Group-2 where each group had 82 patients of comparable age and genders. Group-1 patients were given an intra-lesional injection of sodium Stibogluconate at a dose of 1-5 ml depending on the lesion size, where one ml injection contained 100 mg of the drug. Group-2 patients were given combination therapy of oral Allopurinol (20 mg/kg/day in divided doses) along with the same intra-lesional sodium Stibogluconate dose as group-1 until complete cure of the lesion.
RESULTS
Combination therapy of sodium Stibogluconate along with Allopurinol was found superior to sodium Stibogluconate alone in terms of duration of treatment. Group-1, patients who received only sodium Stibogluconate required prolonged treatment duration of 6-9 weeks depending upon the lesion size, while group-2 patients who received combination therapy of sodium Stibogluconate and Allopurinol responded more quickly and their lesions cured in 3-6 weeks depending upon the lesion size.
CONCLUSIONS
Oral Allopurinol has a synergistic effect when used with intra-lesional sodium Stibogluconate and effectively reduces the treatment duration required for complete cure of cutaneous Leishmaniasis. Treatment duration was reduced by 3 weeks in the present study when combination therapy was given to the patients of cutaneous Leishmaniasis.
Topics: Administration, Oral; Adult; Allopurinol; Antimony Sodium Gluconate; Antiprotozoal Agents; Drug Synergism; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Middle Aged; Single-Blind Method; Young Adult
PubMed: 33225663
DOI: No ID Found -
Acta Dermato-venereologica May 2022The effectiveness of systemic treatment for Leishmania tropica cutaneous leishmaniasis remains unclear. The purpose of the study is to evaluate the efficacy and safety...
The effectiveness of systemic treatment for Leishmania tropica cutaneous leishmaniasis remains unclear. The purpose of the study is to evaluate the efficacy and safety of systemic treatments for L. tropica cutaneous leishmaniasis. This retrospective study was performed in 114 patients. Systemic treatments included liposomal amphotericin B and sodium stibogluconate. All patients underwent systemic treatment for L. tropica cutaneous leishmaniasis. Favourable treatment responses were recorded in 72.5% and 70.2% of the patients in the liposomal amphotericin B and sodium stibogluconate groups, respectively; 25.3% and 46% of those in the liposomal amphotericin B and sodium stibogluconate groups respectively, experienced at least one adverse effect. Lesions in cartilaginous areas were associated with higher treatment failure. Prior topical or systemic treatment increased the chance of future systemic treatment success. Liposomal amphotericin B was associated with a shorter intravenous treatment duration and better safety profile. Thus, liposomal amphotericin B is the treatment of choice for L. tropica cutaneous leishmaniasis.
Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmania tropica; Leishmaniasis, Cutaneous; Retrospective Studies
PubMed: 35229163
DOI: 10.2340/actadv.v102.2079 -
Cureus Mar 2022A combination treatment of cutaneous leishmaniasis (CL) that hastens the healing and reduces the chance of scarring, especially in aesthetically receptive sites, is...
Evaluating the Efficacy of Combined Intralesional Sodium Stibogluconate Plus Topical Imiquimod on Healing and Risk of Scarring of Cutaneous Leishmaniasis: A Case-Control Study.
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.
PubMed: 36158521
DOI: 10.7759/cureus.23200 -
Experimental Parasitology Jan 2021Infection with Leishmania infantum causes the disease visceral leishmaniasis (VL), which is a serious clinical and veterinary problem. The drugs used to treat canine...
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 Sb/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.
Topics: Administration, Intravenous; Analysis of Variance; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Blood Cell Count; Blood Chemical Analysis; Bone Marrow; Cricetinae; Disease Reservoirs; Dogs; Female; Leishmania donovani; Leishmania infantum; Liver; Lymph Nodes; Male; Mesocricetus; Mice; Mice, Inbred BALB C; Paromomycin; Skin; Spleen
PubMed: 33166530
DOI: 10.1016/j.exppara.2020.108033 -
Blood Advances Apr 2022Anti-CD20 antibodies such as rituximab are broadly used to treat B-cell malignancies. These antibodies can induce various effector functions, including immune...
Anti-CD20 antibodies such as rituximab are broadly used to treat B-cell malignancies. These antibodies can induce various effector functions, including immune cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Neutrophils can induce ADCC toward solid cancer cells by trogoptosis, a cytotoxic mechanism known to be dependent on trogocytosis. However, neutrophils seem to be incapable of killing rituximab-opsonized B-cell lymphoma cells. Nevertheless, neutrophils do trogocytose rituximab-opsonized B-cell lymphoma cells, but this only reduces CD20 surface expression and is thought to render tumor cells therapeutically resistant to further rituximab-dependent destruction. Here, we demonstrate that resistance of B-cell lymphoma cells toward neutrophil killing can be overcome by a combination of CD47-SIRPα checkpoint blockade and sodium stibogluconate (SSG), an anti-leishmaniasis drug and documented inhibitor of the tyrosine phosphatase SHP-1. SSG enhanced neutrophil-mediated ADCC of solid tumor cells but enabled trogoptotic killing of B-cell lymphoma cells by turning trogocytosis from a mechanism that contributes to resistance into a cytotoxic anti-cancer mechanism. Tumor cell killing in the presence of SSG required both antibody opsonization of the target cells and disruption of CD47-SIRPα interactions. These results provide a more detailed understanding of the role of neutrophil trogocytosis in antibody-mediated destruction of B cells and clues on how to further optimize antibody therapy of B-cell malignancies.
Topics: Antibody-Dependent Cell Cytotoxicity; Antimony Sodium Gluconate; CD47 Antigen; Neutrophils; Rituximab
PubMed: 34942000
DOI: 10.1182/bloodadvances.2021005367 -
Indian Dermatology Online Journal 2021There has been an upsurge in the cases of cutaneous leishmaniasis over the past few years in the pediatric population of Jammu and Kashmir, hitherto a nonendemic area...
BACKGROUND
There has been an upsurge in the cases of cutaneous leishmaniasis over the past few years in the pediatric population of Jammu and Kashmir, hitherto a nonendemic area for the disease., The aim of this study was to describe the clinico-epidemiological profile and therapeutic outcome of pediatric cutaneous leishmaniasis (PCL) over a 10-year period in J and K.
MATERIALS AND METHODS
An observational study was conducted at two tertiary care hospitals of Jammu and Kashmir over a period of 10 years (July 2010-June 20). Children presenting to the outpatient department with lesions suggestive of CL were enrolled. Patients suspected of having CL based on clinical criteria were subjected to slit skin smears (SSS) and histopathological examination (HPE) for validation of the diagnosis. Intralesional or systemic sodium stibogluconate (SSG) was the treatment modality used for the management of patients. Clinical follow-up was done at intervals of 2 weeks for the first 2 months and monthly thereafter.
RESULTS
A total of 376 cases of CL in children aged 1.5-15 years (mean age 8.4 ± 1.4 years) were included in the study. The duration of the disease ranged from 8 to 52 weeks (mean 22.52 ± 1.5 weeks). Lesions were noted mainly on exposed parts of the body, with face being the most commonly affected site (89.0%). Nodulo-ulcerative plaques were the predominant clinical presentation (62.76%). The diagnosis was confirmed by the demonstration of Leishman Donovan (LD) bodies in 54.25% on SSS- and 25.79% on hematoxylin and eosin -stained tissue sections. In cases where diagnosis could not be confirmed by demonstration of LD body, a histological pattern conforming to CL and response to a therapeutic trial of SSG provided evidence of leishmanial infection. Complete healing was achieved in 95.02% of the cases at the end of treatment.
CONCLUSION
CL is an emerging health problem in the pediatric population of Jammu and Kashmir. Awareness among pediatric health workers regarding this disease and recognition among the differential diagnosis of ulcerated papules or plaques in the pediatric population is imperative.
PubMed: 34934721
DOI: 10.4103/idoj.IDOJ_49_21 -
CNS Neuroscience & Therapeutics Apr 2024Although programmed cell death protein 1 (PD-1) typically serves as a target for immunotherapies, a few recent studies have found that PD-1 is expressed in the nervous...
AIMS
Although programmed cell death protein 1 (PD-1) typically serves as a target for immunotherapies, a few recent studies have found that PD-1 is expressed in the nervous system and that neuronal PD-1 might play a crucial role in regulating neuronal excitability. However, whether brain-localized PD-1 is involved in seizures and epileptogenesis is still unknown and worthy of in-depth exploration.
METHODS
The existence of PD-1 in human neurons was confirmed by immunohistochemistry, and PD-1 expression levels were measured by real-time quantitative PCR (RT-qPCR) and western blotting. Chemoconvulsants, pentylenetetrazol (PTZ) and cyclothiazide (CTZ), were applied for the establishment of in vivo (rodents) and in vitro (primary hippocampal neurons) models of seizure, respectively. SHR-1210 (a PD-1 monoclonal antibody) and sodium stibogluconate (SSG, a validated inhibitor of SH2-containing protein tyrosine phosphatase-1 [SHP-1]) were administrated to investigate the impact of PD-1 pathway blockade on epileptic behaviors of rodents and epileptiform discharges of neurons. A miRNA strategy was applied to determine the impact of PD-1 knockdown on neuronal excitability. The electrical activities and sodium channel function of neurons were determined by whole-cell patch-clamp recordings. The interaction between PD-1 and α-6 subunit of human voltage-gated sodium channel (Nav1.6) was validated by performing co-immunostaining and co-immunoprecipitation (co-IP) experiments.
RESULTS
Our results reveal that PD-1 protein and mRNA levels were upregulated in lesion cores compared with perifocal tissues of surgically resected specimens from patients with intractable epilepsy. Furthermore, we show that anti-PD-1 treatment has anti-seizure effects both in vivo and in vitro. Then, we reveal that PD-1 blockade can alter the electrophysiological properties of sodium channels. Moreover, we reveal that PD-1 acts together with downstream SHP-1 to regulate sodium channel function and hence neuronal excitability. Further investigation suggests that there is a direct interaction between neuronal PD-1 and Nav1.6.
CONCLUSION
Our study reveals that neuronal PD-1 plays an important role in epilepsy and that anti-PD-1 treatment protects against seizures by suppressing sodium channel function, identifying anti-PD-1 treatment as a novel therapeutic strategy for epilepsy.
Topics: Humans; Epilepsy; Hippocampus; Programmed Cell Death 1 Receptor; Seizures; Sodium Channels; Antibodies, Monoclonal, Humanized; NAV1.6 Voltage-Gated Sodium Channel
PubMed: 37904722
DOI: 10.1111/cns.14504