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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 -
Clinical Medicine (London, England) Oct 2011Leishmaniasis is an uncommon infectious disease in the UK with a variety of clinical presentations. Physicians should remember to consider this diagnosis in patients...
Leishmaniasis is an uncommon infectious disease in the UK with a variety of clinical presentations. Physicians should remember to consider this diagnosis in patients with an appropriate travel history (including the Mediterranean basin) and seek help with diagnostics from a specialised parasitology laboratory. Treatment regimens may be unfamiliar to the general physician, and thus should also be discussed with an expert.
Topics: Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Immunocompromised Host; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Middle Aged
PubMed: 22034715
DOI: 10.7861/clinmedicine.11-5-492 -
Journal of Tropical Medicine 2014In the absence of effective vector control measures and vaccines against leishmaniasis, effective chemotherapy remains the mainstay of treatment. As the armoury of... (Review)
Review
In the absence of effective vector control measures and vaccines against leishmaniasis, effective chemotherapy remains the mainstay of treatment. As the armoury of antileishmanial drugs is limited, strategies should be made to target the emergence of drug resistance. The loss of efficacy of antimonials such as sodium stibogluconate in the Indian subcontinent which has been the mainstay of treatment for more than six decades has raised concern to save the other drugs. In the current review, we highlight various steps which could be implemented to halt the increasing unresponsiveness of drugs such as monitoring of therapy in the form of rational dosing and duration of treatment, understanding the mechanism of action of the drugs and drug resistance, identification of markers of resistance, distribution of drugs free of cost, evolution of effective combination therapy and immunotherapy, and proper management of HIV/VL coinfection and post-kala-azar dermal leishmaniasis (PKDL). Strong support from governmental agencies and local communities in the form of education and orientation programmes for feasibility of implementing these strategies and affordability within the context of their health systems is needed in controlling and preventing leishmaniasis.
PubMed: 24876851
DOI: 10.1155/2014/646932 -
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 -
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 -
The Indian Journal of Medical Research Mar 2006Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani and transmitted by the bite of infected sandfly Phlebotomus argentipes. Nearly half... (Review)
Review
Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani and transmitted by the bite of infected sandfly Phlebotomus argentipes. Nearly half of the VL cases occur in children (childhood or paediatric VL). The clinical manifestations of childhood VL are more or less same as in the adults. Prolonged fever with anorexia and loss of appetite are the major presenting features. Marked enlargement of the spleen and liver (spleen larger than liver) with moderate to severe anaemia and changes in hair take place. Bacterial infection is a common coinfection and intestinal parasitic infestations are very common in children with VL. Liver function tests, blood, urine and stool may show abnormalities. Confirmation of diagnosis is made by demonstration of parasite by microscopic examination and culture of materials obtained by bone marrow aspiration or splenic puncture. Sodium antimony gluconate (stibogluconate) has been the drug of choice for over past 50 yr. Pentamidine isothionate, though effective is relatively toxic. Amphotericin B is the most effective drug for the treatment of VL. Miltefosine is the first-ever oral drug, is highly effective. Post kala-azar dermal leishmaniasis (PKDL) in children poses a therapeutic challenge. In the absence of an ideal vaccine for VL, control measures would essentially include prevention of transmission through vector control and community awareness.
Topics: Administration, Oral; Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Leishmania donovani; Leishmaniasis, Visceral; Phosphorylcholine; Psychodidae
PubMed: 16778316
DOI: No ID Found -
Tropical Medicine & International... Dec 2015Among patients with primary and relapse visceral leishmaniasis (VL) in eastern Sudan, we determined the proportion eligible for treatment with sodium stibogluconate and...
OBJECTIVES
Among patients with primary and relapse visceral leishmaniasis (VL) in eastern Sudan, we determined the proportion eligible for treatment with sodium stibogluconate and paromomycin (SSG/PM) and, of these, their demographic and clinical characteristics; initial treatment outcomes including adverse side effects requiring treatment discontinuation; treatment outcomes by 6 months; and risk factors associated with initial (slow responders) and late treatment failure (relapses and post-kala-azar dermal leishmaniasis, PKDL).
METHODS
A retrospective cohort study in Tabarak Allah Hospital, Gedaref Province, eastern Sudan, from July 2011 to January 2014.
RESULTS
Of 1252 individuals diagnosed with VL (1151 primary and 101 relapses), 65% were eligible for SSG/PM including 83% children, almost half of them malnourished and anaemic. About 4% of individuals discontinued treatment due to side effects; 0.7% died during treatment. Initial cure was achieved in 93% of 774 primary cases and 77% of 35 relapse cases (P < 0.001). Among the 809 patients eligible for SSG/PM, 218 (27%) were lost to follow-up. Outcomes by six months among the 591 patients with available follow-up data were: definitive cure (n = 506; 86%), relapse (n = 38; 6%), treatment discontinuation (n = 33; 6%), PKDL (n = 7; 1%) and death (n = 7; 1%). Among those completing a full course of SSG/PM, relapses and under-fives were at significantly higher risk of early and late treatment failure, respectively.
CONCLUSION
Whether SSG/PM as a first-line regimen is an undeniable progress compared to SSG monotherapy, it excluded a considerable proportion of VL patients due to drug safety concerns. We call for accelerated development of new drugs and treatment regimens to improve VL treatment in Sudan.
Topics: Adolescent; Adult; Anemia; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Leishmaniasis, Visceral; Lost to Follow-Up; Male; Malnutrition; Paromomycin; Patient Selection; Prevalence; Recurrence; Retrospective Studies; Sudan; Treatment Failure
PubMed: 26427033
DOI: 10.1111/tmi.12603 -
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 -
Oncotarget Dec 2011Since sodium stibogluconate (SSG) inhibited phosphatases including SHP-1 and augmented anti-tumor actions of IFN-α2b in vitro and in mice, two Phase I trials of...
Since sodium stibogluconate (SSG) inhibited phosphatases including SHP-1 and augmented anti-tumor actions of IFN-α2b in vitro and in mice, two Phase I trials of SSG/IFN-α2b combination were undertaken to evaluate safety and target inhibition. Escalating doses of SSG (200-1200 mg/m2) and fixed doses of IFN-α2b (3x106 units/m2) with or without chemotherapy (dacarbazine, vinblastine, cisplatin) were evaluated for side effects and impact on SHP-1 phospho-substrates and IFNα-stimulated-genes (ISGs) in peripheral blood in 40 patients with metastatic melanoma, soft tissue sarcomas, gastrointestinal stromal tumors, and breast or colorectal carcinomas who did not have other established treatment options. Common adverse events were bone marrow suppression, fatigue, gastrointestinal upset, and asymptomatic lipase elevation (n=13); the latter was dose related and mostly after 10d of SSG/IFN-α2b in combination. Levels of SHP-1 substrates (pSTAT1, pSTAT3, pLck and pSlp76) were increased (up to 3x) in peripheral blood cells following SSG with no potentiation by combination with IFN-α2b. Representative ISGs in peripheral blood were induced after IFN-α2b at 4 and 24 hrs with selective modulations by combination. The median time on trials was 2.3 months (10-281d) with no objective regression of disease. Alive at 1y were 17/40 (43%) patients and after 2y were 8/40 (20%) following treatment initiation. These data demonstrate that SSG impacted signal molecules consistent with PTP inhibition and was tolerated in combination with IFN-α2b. Phase II investigations of SSG could safely utilize doses of up to 1200 mg/m2 of SSG for up to 10d alone or in combination with IFN-α2b with or without chemotherapy.
Topics: Adult; Aged; Antimony Sodium Gluconate; Antineoplastic Agents; Breast Neoplasms; Cisplatin; Colorectal Neoplasms; Dacarbazine; Drug Therapy, Combination; Enzyme Inhibitors; Female; Gastrointestinal Stromal Tumors; Humans; Interferon alpha-2; Interferon-alpha; Male; Melanoma; Middle Aged; Phosphoric Monoester Hydrolases; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Recombinant Proteins; Sarcoma; Vinblastine
PubMed: 22201704
DOI: 10.18632/oncotarget.563