BACKGROUND: The control of cutaneous leishmaniasis (CL) is facilitated by knowledge of factors associated with the treatment failures in endemic countries. The aim of this evaluation was to identify the potential risk determinants which might affect the significance of demographic and clinical characteristics for the patients with anthroponotic CL (ACL) and the outcome of meglumine antimoniate (MA) (Glucantime) treatment. METHODOLOGY/PRINCIPAL FINDINGS: This current was executed as a cohort spanning over a period of 5 years which centered in southeastern part of Iran. Altogether, 2,422 participants were evaluated and 1,391 eligible volunteer patients with ACL caused by Leishmania tropica were included. Overall, 1,116 (80.2%) patients received MA intraleisionally (IL), once a week for 12 weeks along with biweekly cryotherapy, while 275 (19.8%) patients received MA alone (20 mg/kg/day for 3 weeks) (intramuscular, IM). The treatment failure rate in ACL patients was 11% using IL combined with cryotherapy plus IM alone, whilst 9% and 18.5% by IL along with cryotherapy or IM alone, respectively. Multivariate logistic regression model predicted 5 major associated-risk determinants including male (odds ratio (OR) = 1.54, confidence interval (CI) = 1.079-2.22, p = 0.018), lesion on face (OR = 1.574, CI = 1.075-2.303, p = 0.02), multiple lesions (OR = 1.446, CI = 1.008-2.075, p = 0.045), poor treatment adherence (OR = 2.041, CI = 1.204-3.46, p = 0.008) and disease duration > 4 months (OR = 2.739, CI = 1.906-3.936, p≤0.001). CONCLUSIONS/SIGNIFICANCE: The present study is the original and largest cohort of ACL patients who treated with MA. A comprehensive intervention and coordinated action by the health authorities and policy-makers are crucial to make sure that patients strictly follow medical instructions. Early detection and effective therapy < 4 months following the onset of the lesion is critical for successful treatment of the patients. Since a significant number of patients are still refractory to MA, reducing man-vector exposure and development of new effective alternative drugs are essential measures against ACL due to L. tropica.
- MeSH
- antiprotozoální látky terapeutické užití MeSH
- dítě MeSH
- dospělí MeSH
- kohortové studie MeSH
- kojenec MeSH
- kryoterapie metody MeSH
- Leishmania tropica izolace a purifikace MeSH
- leishmanióza kožní farmakoterapie epidemiologie mikrobiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- meglumin antimoniát terapeutické užití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- neúspěšná terapie MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Írán epidemiologie MeSH
- Názvy látek
- antiprotozoální látky MeSH
- meglumin antimoniát MeSH
Leishmaniasis is one of the most important parasitic diseases after malaria. The standard treatment of leishmaniasis includes pentavalent antimonials (SbV); however, these drugs are associated with serious adverse effects. There have been very few studies pertaining to their side effects and mechanism of action in the fetus. This investigation examines the effects of meglumine antimoniate (MA) on the survival rate, angiogenesis and cellular apoptosis in the human umbilical vein endothelial cells (HUVECs). HUVECs were treated with varying doses of MA (100-800 μg/ml) for 24, 48 and 72 h and the survival rate was studied by colorimetric assay, flow cytometry, immunocytochemistry, migration (scratch) assay and tube formation assay. The results of quantitative real-time PCR (qPCR) studies indicated that the most important genes involved in presenting angiogenesis included VEGF and its receptors (Kdr and Flt-1), NP1 and Hif-1α genes including the anti-apoptotic gene of Bcl2, were significantly reduced compared to the control group (p < 0.05). In contrast, the most leading genes involved in the phenomenon of apoptosis were P53, Bax, Bak, Apaf-1 and caspases 3, 8 and 9, which were significantly up regulated compared to the control group (p < 0.05).
- Klíčová slova
- Angiogenesis, Apoptosis, HUVECs, Meglumine antimoniate, Toxicity,
- MeSH
- antiprotozoální látky toxicita MeSH
- apoptóza účinky léků MeSH
- C-reaktivní protein genetika MeSH
- endoteliální buňky pupečníkové žíly (lidské) účinky léků fyziologie MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa genetika MeSH
- fyziologická neovaskularizace účinky léků MeSH
- kultivované buňky MeSH
- lidé MeSH
- meglumin antimoniát toxicita MeSH
- nádorový supresorový protein p53 genetika MeSH
- pohyb buněk účinky léků MeSH
- proteiny nervové tkáně genetika MeSH
- proteiny regulující apoptózu genetika MeSH
- vaskulární endoteliální růstový faktor A genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiprotozoální látky MeSH
- C-reaktivní protein MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
- meglumin antimoniát MeSH
- nádorový supresorový protein p53 MeSH
- neuronal pentraxin MeSH Prohlížeč
- proteiny nervové tkáně MeSH
- proteiny regulující apoptózu MeSH
- vaskulární endoteliální růstový faktor A MeSH
- VEGFA protein, human MeSH Prohlížeč
Currently, there is no satisfactory treatment modality available for cutaneous leishmaniasis (CL). The major objective of the present study was to explore the effect of immunomodulator-levamisole in combination with Glucantime in end-stage unresponsive patients with anthroponotic CL (ACL). Twenty end-stage unresponsive patients with ACL were identified for participation in this single-group trial study. Simultaneously, each patient was received a combination of levamisole pills along with Glucantime during the remedy course. Several in vitro complementary experiments were performed to evaluate the mode of action of levamisole and Glucantime alone and in combination using a macrophage model, in vitro MTT assay, flow cytometry and quantitative real time PCR (qPCR). Overall, 75% of the patients showed complete clinical cure, 10% partially improved and the remaining (15%) had underlying chronic diseases demonstrated no response to the treatment regimen. In in vitro studies, there was no cytotoxic effect associated with these drugs in the range of our experiments. The findings by the flow cytometric analysis represented that the highest apoptotic values corresponded to the drugs combination (32.23%) at 200 μg/ml concentration. Finally, the gene expression level of IL-12 p40, iNOS and TNF-α promoted while the level of IL-10 and TGF-β genes reduced as anticipated. The findings clearly indicated that the combination of levamisole and Glucantime should be considered in end-stage unresponsive patients with ACL who have not responded to basic treatments. The immunomodulatory role of levamisole in mounting immune system as documented by the in vitro experiments and further substantiated by this single-group trail study was highlighted.
- Klíčová slova
- Cutaneous leishmaniasis, End-stage patients, Glucantime, Levamisole, Treatment,
- MeSH
- antiprotozoální látky farmakologie terapeutické užití MeSH
- buněčné linie účinky léků MeSH
- chronická nemoc terapie MeSH
- dítě MeSH
- dospělí MeSH
- fixní kombinace léků MeSH
- interleukin-10 metabolismus MeSH
- interleukin-12 - podjednotka p40 metabolismus MeSH
- kombinovaná farmakoterapie MeSH
- Leishmania tropica účinky léků patogenita MeSH
- leishmanióza kožní farmakoterapie MeSH
- levamisol aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágy účinky léků MeSH
- meglumin antimoniát aplikace a dávkování farmakologie terapeutické užití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- myši MeSH
- senioři MeSH
- synthasa oxidu dusnatého, typ II metabolismus MeSH
- TNF-alfa metabolismus MeSH
- transformující růstový faktor beta metabolismus MeSH
- viabilita buněk účinky léků MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- myši MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiprotozoální látky MeSH
- fixní kombinace léků MeSH
- IL10 protein, human MeSH Prohlížeč
- interleukin-10 MeSH
- interleukin-12 - podjednotka p40 MeSH
- levamisol MeSH
- meglumin antimoniát MeSH
- NOS2 protein, human MeSH Prohlížeč
- synthasa oxidu dusnatého, typ II MeSH
- TNF-alfa MeSH
- transformující růstový faktor beta MeSH
Leishmaniasis is an infectious disease caused by parasitic flagellates of the genus Leishmania. The authors present a case of 44-year-old man with Crohn's disease treated successfully with infliximab. This case report shows rare visceral leishmaniasis with cutaneous symptoms in an immunocompromised patient. Skin manifestations may occur before or after the visceral infection and they are often diverse.
- Klíčová slova
- immunosuppression, skin manifestation, visceral leishmaniasis,
- MeSH
- antiflogistika škodlivé účinky MeSH
- antiprotozoální látky škodlivé účinky MeSH
- Crohnova nemoc diagnóza farmakoterapie imunologie MeSH
- dospělí MeSH
- fatální výsledek MeSH
- gastrointestinální látky škodlivé účinky MeSH
- imunokompromitovaný pacient MeSH
- infliximab MeSH
- leishmanióza kožní chemicky indukované diagnóza farmakoterapie imunologie parazitologie MeSH
- leishmanióza viscerální chemicky indukované diagnóza farmakoterapie imunologie parazitologie MeSH
- lidé MeSH
- meglumin antimoniát MeSH
- meglumin škodlivé účinky MeSH
- monoklonální protilátky škodlivé účinky MeSH
- organokovové sloučeniny škodlivé účinky MeSH
- srdeční arytmie chemicky indukované MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiflogistika MeSH
- antiprotozoální látky MeSH
- gastrointestinální látky MeSH
- infliximab MeSH
- meglumin antimoniát MeSH
- meglumin MeSH
- monoklonální protilátky MeSH
- organokovové sloučeniny MeSH
