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1.
Exp Parasitol ; 220: 108033, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33166530

RESUMO

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.


Assuntos
Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmania donovani/efeitos dos fármacos , Leishmania infantum/efeitos dos fármacos , Paromomicina/uso terapêutico , Administração Intravenosa , Análise de Variância , Animais , Gluconato de Antimônio e Sódio/administração & dosagem , Gluconato de Antimônio e Sódio/farmacologia , Antiprotozoários/administração & dosagem , Antiprotozoários/farmacologia , Contagem de Células Sanguíneas , Análise Química do Sangue , Medula Óssea/parasitologia , Cricetinae , Reservatórios de Doenças , Cães , Feminino , Leishmania donovani/imunologia , Leishmania donovani/isolamento & purificação , Leishmania infantum/imunologia , Leishmania infantum/isolamento & purificação , Fígado/parasitologia , Linfonodos/parasitologia , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Paromomicina/administração & dosagem , Paromomicina/farmacologia , Pele/parasitologia , Baço/parasitologia
3.
Int J Infect Dis ; 98: 166-175, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32579907

RESUMO

OBJECTIVES: With the increasing number of people suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a dire need to look for effective remedies against this pandemic. Drug repurposing seems to be the solution for the current situation. METHODS: In a quest to find a potential drug against this virus, 15 antimalarial drugs (including chloroquine) and 2413 US Food and Drug Administration-approved drugs were investigated for activity against both the protease and spike proteins of SARS-CoV-2 using an in silico approach. Molecular docking analysis followed by molecular dynamics simulation was performed to estimate the binding and stability of the complexes. RESULTS: This study identified a single drug - paromomycin - with activity against two targets of SARS-CoV-2, i.e., spike protein (S1) and protease domain. Paromomycin was found to have strong binding affinity for both targets of coronavirus. The results also showed that no antimalarial drug exhibited effective binding for either S1 or protease. CONCLUSIONS: This study found that paromomycin may be an effective dual targeting drug against coronavirus, as it binds not only to the protease domain of the virion, but also to the spike domain, with high stability. Furthermore, none of the antimalarial drugs showed strong binding affinity for either protease or the receptor binding domain (RBD).


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Paromomicina/uso terapêutico , Peptídeo Hidrolases/metabolismo , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Betacoronavirus/metabolismo , Simulação por Computador , Reposicionamento de Medicamentos , Humanos , Simulação de Acoplamento Molecular , Pandemias , Peptídeo Hidrolases/química , Ligação Proteica
4.
Exp Parasitol ; 214: 107903, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32360142

RESUMO

The aim of this 6-month, randomized, blinded, controlled clinical trial was to compare the efficacy and safety of aminosidine-allopurinol combination with that of meglumine antimoniate-allopurinol combination for the treatment of leishmaniosis in dogs without stage III or IV chronic kidney disease. Forty client-owned dogs were randomly assigned to group A [n = 20; aminosidine (15 mg/kg, subcutaneously, once daily, for 28 days) and allopurinol (10 mg/kg, per os, twice daily, for 6 months)] or group B [(n = 20; meglumine antimoniate (100 mg/kg SC, once daily, for 28 days) and allopurinol (10 mg/kg, per os, twice daily, for 6 months)]. Clinical and clinicopathological evaluations, parasitic load measurement (lymph node and bone marrow microscopy, bone marrow real-time PCR), specific serology and leishmanin skin test (LST) were performed at baseline (time 1) and after 14 (time 2), 28 (time 3), 60 (time 4) and 180 (time 5) days. Both treatments were safe and resulted in significant clinical and clinicopathological improvement, reduction of parasitic load and of indirect immunofluorescence antibody test (IFAT) titer and induction of positive LST. There was no significant difference between groups with regards to the primary outcome measures of the trial that included the proportion of dogs that presented severe treatment-related side effects, were cured and were parasitologically negative at time 5. However, some (proportion of dogs that presented no clinical signs, no hyperglobulinemia and negative serology at time 5) secondary outcome measures showed significant differences in favor of the meglumine antimoniate-allopurinol treatment arm. Treatment-related death occurred in one dog in each group, while injection site reactions appeared at a similar frequency in both groups. Due to the differences in some secondary outcome measures in association with the low power of this trial, it cannot be definitively concluded that the two treatments are equally effective. Therefore, the aminisodine-allopurinol combination cannot be proposed as a first-line treatment of CanL but rather as a second-line treatment that may be particularly useful to avoid repeated administration of meglumine antimoniate and in countries where the latter is not available or registered.


Assuntos
Alopurinol/uso terapêutico , Doenças do Cão/tratamento farmacológico , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Antimoniato de Meglumina/uso terapêutico , Paromomicina/uso terapêutico , Tripanossomicidas/uso terapêutico , Animais , Cães , Quimioterapia Combinada , Feminino , Injeções Subcutâneas/veterinária , Masculino
5.
Turkiye Parazitol Derg ; 44(1): 12-16, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32212583

RESUMO

Objective: Meglumine antimoniate (Glucantime®) and Sodium stibogluconate (Pentostam®) are used for the treatment of cutaneous leismaniasis in Turkey. There is a reported resistance to these drugs in recent years. The aim of the present study was to compare the in vitro sensitivities of resistant Leishmania isolates against Amphotericin B, Miltefosine, Meglumine Antimoniate, Paromomycin and Sodium Stibogluconate. Methods: Five Leishmania isolates of patients with cutaneous leishmaniasis, who showed no clinical recovery despite two consecutive meglumine antimoniate treatments, which were stored in the Parasite Bank in Manisa Celal Bayar University Medical Faculty were selected. They were genotyped with Real-Time PCR using specific primers and probes to ITS1 region. Drug resistance levels of each Leishmania isolate were analysed for Amphotericin B, Miltefosine, Meglumine Antimoniate, Paromomycin, and Sodium Stibogluconate at concentrations of 500, 250, 125, 50, 25 µg/mL with XTT method and hemocytometer. Results: It was observed that the resistant Leishmania tropica isolates showed no resistance to Amphotericin B, and were sensitive to Miltefosine, Sodium Stibogluconate, Paromomycin and Meglumin Antimonate, respectively. In addition, Leishmania tropica (MHOM/AZ/1974/SAF-K27) isolate of the control group could stay viable in none of the drug concentrations of five agents in the study. Conclusion: It was determined that none of the selected resistant L. tropica isolates showed resistance to Amphotericin B and that was also shown statistically (p<0.05). The results of this study are important in guiding clinicians and researchers who conduct studies on drugs and search for new drug molecules.


Assuntos
Antiprotozoários/farmacologia , Leishmania/efeitos dos fármacos , Leishmaniose Cutânea/parasitologia , Anfotericina B/administração & dosagem , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Animais , Gluconato de Antimônio e Sódio/administração & dosagem , Gluconato de Antimônio e Sódio/farmacologia , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Resistência a Medicamentos , Feminino , Técnicas de Genotipagem , Humanos , Leishmania/classificação , Leishmania/genética , Leishmaniose Cutânea/tratamento farmacológico , Masculino , Antimoniato de Meglumina/farmacologia , Antimoniato de Meglumina/uso terapêutico , Paromomicina/administração & dosagem , Paromomicina/farmacologia , Paromomicina/uso terapêutico , Fosforilcolina/administração & dosagem , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Turquia
6.
Diagnosis (Berl) ; 7(1): 69-73, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31256063

RESUMO

Background Liver abscess is the most common extraintestinal manifestation of Entamoeba histolytica. Clinical manifestations could appear after returning from an endemic area or several years after the exposure. The diagnosis usually requires microbiological confirmation. Case presentation We present a case of a 55-year-old woman diagnosed with Crohn's disease treated with immunosuppressive drugs, who was admitted to the Emergency Service with liver parenchyma abscesses. Computed tomography (CT)-guided puncture showed pus, and both Gram staining and fresh parasite visualization were negative. Hepatic pus bacteriological culture was reported as negative and parasite multiplex polymerase chain reaction (PCR) was performed, being positive for E. histolytica. The same PCR was performed on blood, pleural fluid and stool samples, all of them being positive for E. histolytica. Conclusions Reviewing the clinical history of this patient, it was observed that parasite detection in three stool samples was negative 2 months before the current admission. Due to the lack of sensitivity of the microscopy techniques, we propose to routinely perform parasite detection in stools using molecular techniques, especially in immunocompromised patients.


Assuntos
Entamoeba histolytica/genética , Fezes/parasitologia , Abscesso Hepático/parasitologia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Cefotaxima/administração & dosagem , Cefotaxima/uso terapêutico , Feminino , Humanos , Hospedeiro Imunocomprometido , Enteropatias Parasitárias/complicações , Abscesso Hepático/diagnóstico por imagem , Abscesso Hepático/terapia , Metronidazol/administração & dosagem , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Paromomicina/administração & dosagem , Paromomicina/uso terapêutico , Reação em Cadeia da Polimerase/métodos , Punções/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
7.
Artigo em Inglês | MEDLINE | ID: mdl-31759244

RESUMO

Dientamoeba fragilis is a trichomonad parasite of the human intestine that is found worldwide. However, the biological cycle and transmission of this parasite have yet to be elucidated. Although its pathogenic capacity has been questioned, there is increasing evidence that clinical manifestations vary greatly. Different therapeutic options with antiparasitic drugs are currently available; however, very few studies have compared the effectiveness of these drugs. In the present longitudinal study, we evaluate 13,983 copro-parasitological studies using light microscopy of stools, during 2013-2015, in Terrassa, Barcelona (Spain). A total of 1150 (8.2%) presented D. fragilis. Of these, 739 episodes were finally analyzed: those that involved a follow-up parasitology test up to 3 months later, corresponding to 586 patients with gastrointestinal symptoms (53% under 15 years of age). Coinfection by Blastocystis hominis was present in 33.6% of the subjects. Our aim was to compare therapeutic responses to different antiparasitic drugs and the factors associated with the persistence of D. fragilis post-treatment. Gender, age, and other intestinal parasitic coinfections were not associated with parasite persistence following treatment. Metronidazole was the therapeutic option in most cases, followed by paromomycin: 65.4% and 17.5% respectively. Paromomycin was found to be more effective at eradicating parasitic infection than metronidazole (81.8% vs. 65.4%; p = 0.007), except in children under six years of age (p = 0.538). Although Dientamoeba fragilis mainly produces mild clinical manifestations, the high burden of infection means we require better understanding of its epidemiological cycle and pathogenicity, as well as adequate therapeutic guidelines in order to adapt medical care and policies to respond to this health problem.


Assuntos
Antiprotozoários/uso terapêutico , Dientamebíase/tratamento farmacológico , Metronidazol/uso terapêutico , Paromomicina/uso terapêutico , Adolescente , Adulto , Criança , Dientamoeba/efeitos dos fármacos , Fezes/parasitologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Espanha , Resultado do Tratamento , Adulto Jovem
8.
PLoS Negl Trop Dis ; 13(9): e0007726, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31557162

RESUMO

BACKGROUND: An earlier open label, prospective, non-randomized, non-comparative, multi-centric study conducted within public health facilities in Bihar, India (CTRI/2012/08/002891) measured the field effectiveness of three new treatment regimens for visceral leishmaniasis (VL): single dose AmBisome (SDA), and combination therapies of AmBisome and miltefosine (AmB+Milt) and miltefosine and paromomycin (Milt+PM) up to 6 months follow-up. The National Vector Borne Disease Control Program (NVBDCP) recommended an extended follow up at 12 months post-treatment of the original study cohort to quantify late relapses. METHODS: The 1,761 patients enrolled in the original study with the three new regimens were contacted and traced between 10 and 36 months following completion of treatment to determine their health status and any occurrence of VL relapse. RESULTS: Of 1,761 patients enrolled in the original study, 1,368 were traced at the extended follow-up visit: 711 (80.5%), 295 (83.2%) and 362 (71.5%) patients treated with SDA, AmB+Milt and Milt+PM respectively. Of those traced, a total of 75 patients were reported to have relapsed by the extended follow-up; 45 (6.3%) in the SDA, 25 (8.5%) in the AmB+Milt and 5 (1.4%) in the Milt+PM arms. Of the 75 relapse cases, 55 had already been identified in the 6-months follow-up and 20 were identified as new cases of relapse at extended follow-up; 7 in the SDA, 10 in the AmB+Milt and 3 in the Milt+PM arms. CONCLUSION: Extending follow-up beyond the standard 6 months identified additional relapses, suggesting that 12-month sentinel follow-up may be useful as a programmatic tool to better identify and quantify relapses. With limited drug options, there remains an urgent need to develop effective new chemical entities (NCEs) for VL.


Assuntos
Antiprotozoários/uso terapêutico , Leishmaniose Visceral/tratamento farmacológico , Adolescente , Anfotericina B/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Índia , Masculino , Paromomicina/uso terapêutico , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapêutico , Recidiva , Resultado do Tratamento
9.
Exp Parasitol ; 206: 107768, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31539540

RESUMO

Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I-V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.


Assuntos
Alopurinol/efeitos adversos , Doenças do Cão/tratamento farmacológico , Audição/efeitos dos fármacos , Rim/efeitos dos fármacos , Leishmaniose Visceral/veterinária , Paromomicina/efeitos adversos , Alopurinol/administração & dosagem , Alopurinol/uso terapêutico , Animais , Cóclea/efeitos dos fármacos , Creatinina/sangue , Doenças do Cão/parasitologia , Cães , Método Duplo-Cego , Combinação de Medicamentos , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Perda Auditiva/induzido quimicamente , Perda Auditiva/veterinária , Injeções Subcutâneas/veterinária , Leishmania infantum , Leishmaniose Visceral/tratamento farmacológico , Masculino , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/efeitos adversos , Antimoniato de Meglumina/uso terapêutico , Exame Neurológico/veterinária , Paromomicina/administração & dosagem , Paromomicina/uso terapêutico , Distribuição Aleatória , Vestíbulo do Labirinto/efeitos dos fármacos
10.
Acta Trop ; 197: 105045, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158341

RESUMO

Cutaneous leishmaniasis is the most common form of leishmaniasis caused by different species of Leishmania parasites. The emergence of resistance, toxicity, long term treatment, high cost of the current drugs, and intracellular nature of the parasite are the major difficulties for the treatment of leishmaniasis. Although the therapeutic effect of paromomycin (PM) on leishmaniasisLeishmania parasite). PM-loaded into mannosylated CS (MCS) nanoparticles using dextran (PM-MCS-dex-NPs) was prepared by ionic gelation and then characterized. The particle size and Zeta potential of PM-MCS-dex-NPs were obtained as 246 nm and + 31 mV, respectively. Mannosylation of CS was qualitatively evaluated by Fourier-transform infrared spectroscopy and quantitatively measured by CHNO elemental analysis; also, a mannosylation level of 17% (w) was attained. Encapsulation efficiency (EE), drug release profile, and THP-1 cell uptake potential were determined. A value of 83.5% for EE and a higher release rate in acidic media were achieved. THP-1 cell uptake level of PM-MCS-dex-NPs after 6 h was ˜2.8 and ˜3.9 times of non-mannosylated CS nanoparticles (PM-CS-dexIn vitroGlucantim, PM-CS-dex-NPs, and PM-MCS-dex-NPs after 48 h were obtained as 1846 ±â€¯158, 1234 ±â€¯93, 784 ±â€¯52 and 2714 ±â€¯126 µg mL-1Glucantim, PM-CS-dex-NPs, and PM-MCS-dex-NPs after 48 h were obtained as 105.0 ±â€¯14.0, 169.5 ±â€¯9.8, 65.8 ±â€¯7.3 and 17.8 ±â€¯1.0 µg mL-1Glucantim, PM-CS-dex-NPs and PM-MCS-dexGlucantim, PM-CS-dex-NPs, and PM-MCS-dex-NPs at a typical concentration of 20 µg mL-1 were 71.78, 69.94, 83.14 and 33.41%, respectively. While the effect of PM-CS-dex-NPs was more salient on amastigotes, PM-MCS-dex-NPs effectively affected both stages of the parasite, especially the amastigote one. This indicated that the mannosylated formulation acts as a targeted delivery system. The findings of this study revealed that this novel targeted formulation represented a strong anti-leishmanial activity.


Assuntos
Quitosana , Sistemas de Liberação de Medicamentos , Leishmaniose/tratamento farmacológico , Nanopartículas , Paromomicina/administração & dosagem , Paromomicina/uso terapêutico , Animais , Quitosana/síntese química , Quitosana/química , Nanopartículas/química , Espectroscopia de Infravermelho com Transformada de Fourier
11.
Infez Med ; 27(1): 58-67, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30882380

RESUMO

Five-nitroimidazole (5-NI) compounds are among the most commonly used medications in the treatment of giardiasis. However, after more than five decades of their initial indication for such treatment, there are some concerns about the efficacy of 5-NIs in giardiasis. This study sought to compare the efficacy of any 5-NI with any other antigiardial drug for the treatment of Cuban children with giardiasis. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched CUMED, EBSCOhost and PubMed databases. Two reviewers independently assessed trial eligibility, trial quality and extracted appropriate data. The primary outcome was the parasitological cure. The effect estimate was the pooled relative risk (RR) with 95% confidence intervals (CI). We included seven RCTs in the systematic review, involving a total of 1046 children. When the effect of 5-NIs was compared with that of benzimidazole compounds, the pooled effect was significant and favored 5-NIs [the relative risk (RR) is 1.35, 95% CI =1.05 to 1.75], with high heterogeneity (4 studies, I2 =79%). Compared with chloroquine, the pooled effects of the 5-NIs were not significant [RR is 0.96, 95% CI=0.79 to 1.18, (2 studies, I2=68%)]. Our results support the use of 5-NIs (mainly tinidazole) as first-line therapy for Cuban pediatric patients infected with Giardia and may continue being used as reference drugs in future RCTs of giardiasis. These data could help inform policy decisions in Cuba. Caution is needed in extrapolating such data in other settings.


Assuntos
Antiprotozoários/uso terapêutico , Benzimidazóis/uso terapêutico , Giardíase/tratamento farmacológico , Nitroimidazóis/uso terapêutico , Criança , Cloroquina/uso terapêutico , Cuba , Humanos , Paromomicina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tiazóis/uso terapêutico , Tinidazol/uso terapêutico , Resultado do Tratamento
12.
Exp Anim ; 68(3): 285-292, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-30814394

RESUMO

There are few effective antimicrobial agents against Balantidium coli infection. The effect of paromomycin sulfate (PS) against B. coli was confirmed in this study of 596 captive cynomolgus monkeys. In several trials, the minimum dose and duration of oral administration of PS were 25 mg/day for 5 + 5 days, with a 2-day withdrawal interval. To facilitate daily PS administration, pumpkin cakes supplemented with PS were made, which not only resulted in precise effects but also increased the efficiency of preparation and administration of PS by the animal care staff. No cysts or trophozoites were detected at 14 or 16 days after the last treatments. There were no obvious differences in blood and biochemical parameters between before and after administration of PS. These results indicate that PS is effective for elimination of B. coli without hematological side effects. These data could contribute to the control of microbiological pathogens during veterinary care and colony management in primate facilities.


Assuntos
Antiprotozoários/uso terapêutico , Balantidíase/tratamento farmacológico , Macaca fascicularis , Doenças dos Macacos/tratamento farmacológico , Paromomicina/uso terapêutico , Animais , Balantidium/efeitos dos fármacos , Fezes/parasitologia , Feminino , Masculino
13.
Nanomedicine (Lond) ; 14(4): 387-406, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30688557

RESUMO

AIM: The present study evaluates the efficacy of paromomycin (PM)-loaded mannosylated thiomeric nanoparticles for the targeted delivery to pathological organs for the oral therapy of visceral leishmaniasis. MATERIALS & METHODS: Mannosylated thiolated chitosan (MTC)-coated PM-loaded PLGA nanoparticles (MTC-PLGA-PM) were synthesized and evaluated for morphology, drug release, permeation enhancing and antileishmanial potential. RESULTS: MTC-PLGA-PM were spherical in shape with a size of 391.24 ± 6.91 nm and an encapsulation efficiency of 67.16 ± 14%. Ex vivo permeation indicated 12.73-fold higher permeation of PM with MTC-PLGA-PM against the free PM. Flow cytometry indicated enhanced macrophage uptake and parasite killing in Leishmania donovani infected macrophage model. In vitro antileishmanial activity indicated 36-fold lower IC50 for MTC-PLGA-PM as compared with PM. The in vivo studies indicated 3.6-fold reduced parasitic burden in the L. donovani infected BALB/c mice model. CONCLUSION: The results encouraged the concept of MTC-PLGA-PM nanoparticles as promising strategy for visceral leishmaniasis.


Assuntos
Leishmaniose Visceral/tratamento farmacológico , Nanopartículas/química , Paromomicina/química , Paromomicina/uso terapêutico , Animais , Antiprotozoários/administração & dosagem , Antiprotozoários/química , Antiprotozoários/uso terapêutico , Células Cultivadas , Citometria de Fluxo , Lectinas Tipo C/metabolismo , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/patogenicidade , Leishmaniose Visceral/metabolismo , Lectinas de Ligação a Manose/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Paromomicina/administração & dosagem , Receptores de Superfície Celular/metabolismo
15.
Am J Trop Med Hyg ; 100(2): 306-310, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30628567

RESUMO

Local therapies have been proposed as safe and effective alternatives to systemic drugs in cutaneous leishmaniasis (CL), especially among less severe cases. However, they are not widely available and used in endemic places, including Colombia, which has a high burden of disease. Further complicating the uptake of local therapies is that different treatment guidelines have been established by the World Health Organization (WHO) and Pan American Health Organization (PAHO). Using data from a large referral center in Colombia, we determined the proportion of patients who would be eligible for and potentially benefit from local therapies according to both international guidelines. The sample included 1,891 confirmed cases of CL aged ≥ 12 years, mostly infected with Leishmania Viannia panamensis (91%, n = 601/660), between 2004 and 2014. Overall, 57% of the sample had one lesion, whereas another 31% had two to three lesions. For 74% of patients, all lesions were in an area other than head or neck. The maximum lesion size was ≤ 3 cm for 58% and < 5 cm for 88% of the sample. Based on our data, up to 56% of patients could have been eligible for local therapies according to the WHO criteria. By contrast, only 23% were eligible according to the more restrictive PAHO criteria. Regardless, these data suggest that a substantial proportion of CL patients in Colombia may benefit from local therapies given their relatively mild presentation of disease and low risk of complications. Individualized risk-benefit assessment and guideline adjustments may increase local therapy eligibility and benefit a large number of patients.


Assuntos
Antimônio/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmania braziliensis/efeitos dos fármacos , Leishmania guyanensis/efeitos dos fármacos , Leishmaniose Cutânea/terapia , Paromomicina/uso terapêutico , Pentamidina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Colômbia/epidemiologia , Estudos Transversais , Crioterapia/métodos , Feminino , Humanos , Hipertermia Induzida/métodos , Leishmania braziliensis/crescimento & desenvolvimento , Leishmania braziliensis/patogenicidade , Leishmania guyanensis/crescimento & desenvolvimento , Leishmania guyanensis/patogenicidade , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/parasitologia , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Índice de Gravidade de Doença
16.
Enferm Infecc Microbiol Clin ; 37(5): 290-295, 2019 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30274823

RESUMO

INTRODUCTION: The characteristics of D. fragilis infection are described, with special focus on the clinical and epidemiological aspects. MATERIALS AND METHODS: A retrospective and descriptive study was performed, including all the patients with Dientamoeba fragilis infection who attended a specialized unit between January 2012 and December 2017. PCR was used to diagnose D. fragilis. Patients were treated with metronidazole or paromomycin and reviewed at four and eight weeks post-treatment. Cure was defined as the negativization of all parasitological tests, in absence of symptoms. RESULTS: 163 patients were diagnosed. The most frequent symptoms were abdominal pain (36.2%), chronic diarrhoea (12.3%), anal itching (10.4%), abdominal discomfort (9.2%), skin disease (8%), acute diarrhoea (4.3%) and vomiting (4.3%). Fifty patients were asymptomatic. Forty-two patients had eosinophilia in blood. Thirty-eight cases (23.3%) had a coinfection by Enterobius vermicularis. One hundred and seven patients received treatment, sixty-one of them with metronidazole and the rest with paromomycin. Ninety-nine patients (91%) were cured. The rate of cure was 100% in the paromomycin group versus 86.8% in the metronidazole group (p=0.005; OR: 1.173 [1.057-1.302]). The absence of cure was associated with E. vermicularis coinfection (p=0.014; OR: 6.167 [1.432-26.563] and with longer duration of the symptoms (175 [±159SD]) versus 84 [±88SD] days, p=0.014) but multivariable analysis did not confirm these associations. CONCLUSION: Dientamoeba fragilis is an important and underestimated cause of gastrointestinal disease in both the autochthonous and immigrant or traveller population. More studies are needed to clarify its optimal treatment and the role played by E. vermicularis in its transmission and maintenance.


Assuntos
Dientamebíase , Adulto , Antiprotozoários/uso terapêutico , Dientamebíase/diagnóstico , Dientamebíase/tratamento farmacológico , Dientamebíase/epidemiologia , Feminino , Humanos , Masculino , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Paromomicina/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
17.
Clin Infect Dis ; 68(5): 844-849, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30260376

RESUMO

BACKGROUND: Cutaneous leishmaniasis (CL) presents as 1 or more skin lesions, which makes local therapy inherently attractive compared to systemic therapy that exposes the whole body to a drug. For 30 years, 15% paromomycin topical formulations have been in clinical experimentation. Recently, 15% paromomycin in Aquaphilic, a complex base to facilitate adsorption into the lesion, was found superior to aquaphilic vehicle for Old World Leishmania major disease. METHODS: We performed a randomized trial of 15% paromomycin in Aquaphilic (40 patients) vs Aquaphilic vehicle (20 patients) vs a positive control (intralesional pentamidine; 20 patients) against L. braziliensis CL in Bolivia. RESULTS: Cure rates after 6 months of follow-up were 31 of 40 (77.5%, 95% confidence interval [CI] 62.5-88%) for paromomycin-Aquaphilic, 2 of 20 (10%, 95% CI 3-30%) for Aquaphilic vehicle (P < .0001 vs paromomycin-Aquaphilic), and 14 of 20 (70%, 95% CI 48-85.5%) for intralesional pentamidine. Both paromomycin-Aquaphilic and the Aquaphilic vehicle were very well tolerated, with only grade 1 adverse reactions in 5-10% of patients. CONCLUSIONS: Against L. braziliensis CL, a prevalent, aggressive form of New World CL, 15% paromomycin-aquaphilic was vastly superior to a negative vehicle control and was comparable in efficacy to a positive control. This study enlarges the potential use of 15% paromomycin-Aquaphilic from one form of Old World CL to CL more generally. CLINICAL TRIALS REGISTRATION: NCT03096457.


Assuntos
Antiprotozoários/uso terapêutico , Leishmania braziliensis , Leishmaniose Cutânea/tratamento farmacológico , Paromomicina/uso terapêutico , Administração Tópica , Adulto , Antiprotozoários/administração & dosagem , Humanos , Paromomicina/administração & dosagem , Pentamidina/administração & dosagem , Pentamidina/uso terapêutico , Adulto Jovem
19.
Sex Transm Dis ; 46(1): e1-e2, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30106840

RESUMO

Metronidazole-resistant trichomoniasis is an uncommon condition that presents significant therapeutic challenges. Combination therapy with high-dose oral tinidazole and vaginal paromomycin cream has been uniformly successful. We present a case report of a patient who responded to combination therapy with high-dose oral tinidazole and intravaginal paromomycin.


Assuntos
Metronidazol/uso terapêutico , Tinidazol/uso terapêutico , Vaginite por Trichomonas/tratamento farmacológico , Trichomonas vaginalis/efeitos dos fármacos , Administração Intravaginal , Administração Oral , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Paromomicina/uso terapêutico , Resultado do Tratamento , Vaginite por Trichomonas/diagnóstico , Vagina/parasitologia
20.
J Zoo Wildl Med ; 49(4): 1061-1063, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30592920

RESUMO

Feces collected from a wild-caught, young adult king cobra ( Ophiophagus hannah) were repeatedly positive for Cryptosporidium on both direct immunofluorescent antibody (DFA) and polymerase chain reaction (PCR), and sequencing identified the organism as Cryptosporidium serpentis. Infection was subclinical, as the snake was in good body condition and active, and readily consumed dead rats that were scented with snake skin. A course of paromomycin, inserted in feeder rats, was initiated at 360 mg/kg, orally, twice weekly for 6 wk. Feces collected at the end of treatment were negative for Cryptosporidium on PCR, as were feces collected 3 wk, 6 mo, 12 mo, and 18 mo later. At higher dosages, paromomycin may prove useful and may be curative for early gastric and intestinal cryptosporidiosis in squamate reptiles.


Assuntos
Antiprotozoários/uso terapêutico , Criptosporidiose/tratamento farmacológico , Cryptosporidium/isolamento & purificação , Ophiophagus hannah , Paromomicina/uso terapêutico , Animais , Animais de Zoológico , Criptosporidiose/parasitologia , Resultado do Tratamento
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