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1.
BMC Infect Dis ; 20(1): 645, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873242

RESUMO

BACKGROUND: During the outbreak of cutaneous leishmaniasis in the Kurdistan Region of Iraq that started in 2015, the course of the disease and the treatment were not consistent with the available literature. Physicians, particularly dermatologists, faced challenges with treating the cutaneous leishmaniasis lesions with high rates of treatment failure and resistance to treatment. We used Q-methodology to understand the range and diversities of opinions and the practical experiences of dermatologists about the treatment difficulties of cutaneous leishmaniasis. METHODS: This Q-methodology study was carried out in Erbil, Kurdistan Region of Iraq, and involved 37 dermatologists. A set of 40 statements related to different aspects of difficulties and uncertainties of treating cutaneous leishmaniasis was prepared. The dermatologists were requested to distribute the 40 statements into a scaled grid of nine piles from least agree to most agree. We applied by-person factor analysis using PQMethod 2.35 for the data analysis. RESULTS: The analysis revealed two different viewpoints about the treatment of cutaneous leishmaniasis and a consensus viewpoint. The first viewpoint emphasized the use of sodium stibogluconate-based combination therapy, concerns with treatment failure, and lack of compliance with the treatment. The second viewpoint emphasized the lack of standard treatment and advances in the treatment of cutaneous leishmaniasis. There was a consensus between both groups of respondents about many aspects of the treatment of cutaneous leishmaniasis, including considering sodium stibogluconate the first drug of choice for cutaneous leishmaniasis treatment. CONCLUSIONS: This study revealed a diversity of viewpoints and uncertainties about the effectiveness of the available treatment modalities and treatment difficulties and failure. Interrupted supply and poor quality of the available drugs and lack of a standard and advanced treatment are the main problems facing the treatment of cutaneous leishmaniasis. More research is required to determine the best treatment modalities for the different types of cutaneous leishmaniasis. There is a need for the development of treatment guidelines specific to the Iraqi context with a particular focus on the treatment of the resistant and atypical cases of cutaneous leishmaniasis.


Assuntos
Gluconato de Antimônio e Sódio/uso terapêutico , Atitude , Consenso , Dermatologistas/psicologia , Leishmania , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/epidemiologia , Adulto , Terapia Combinada , Análise Fatorial , Feminino , Humanos , Incidência , Iraque/epidemiologia , Leishmaniose Cutânea/parasitologia , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Falha de Tratamento
2.
Am J Trop Med Hyg ; 103(4): 1490-1492, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32720633

RESUMO

Human visceral leishmaniasis (HVL) is a parasitic disease infecting children in the Mediterranean region. Here, we portray a case of a 2-year-old child with an epidemiological description of the situation surrounding the case. The patient was suffering from recurrent fever, weakness, and abdominal discomfort associated with loss of appetite. Routine blood investigations showed pancytopenia, whereas examination revealed hepatomegaly. A diagnosis of HVL was made by demonstrating amastigotes in a Giemsa-stained smear from a bone marrow aspirate followed by genotyping by PCR and sequencing. In conclusion, early detection of VL infection followed by appropriate treatment protocols is essential to saving the patient.


Assuntos
Medula Óssea/parasitologia , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral , Animais , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Pré-Escolar , Reservatórios de Doenças , Cães/parasitologia , Diagnóstico Precoce , Feminino , Humanos , Insetos Vetores , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/patologia , Oriente Médio/epidemiologia , Phlebotomus/parasitologia
3.
Exp Parasitol ; 217: 107948, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32698076

RESUMO

Immunomodulation is an emerging concept to combat infection in recent years. Immunomodulators like arabinosylated-lipoarabinomannan (Ara-LAM) and glycyrrhizic-acid (GA) possess anti-leishmanial property, whereas sodium-antimony-gluconate (SAG) is still considered as the first choice for chemotherapy against leishmaniasis. During infection, invasion of Leishmania donovani needs the potential requirement of Ca2+, which is further responsible for apoptosis in intracellular amastigotes. However, suppression of elevated intracellular calcium by the activation of plasma-membrane-calcium-ATPase (PMCA4) facilitates survival of L. donovani in the host. In the present study, SAG, Ara-LAM, and GA were found to evoke significant increase in intracellular Ca2+ in L. donovani infected macrophages by inhibiting PMCA4. Moreover, PMCA4 inhibition by TFP or PMCA4 siRNA elevated the level of PKCß, whereas calcium-independent upregulation of PKCζ remained unchanged in infected macrophages. Furthermore, application of immunomodulators in infected macrophages resulted in down-regulation of PKCζ, conversion of anti-inflammatory to pro-inflammatory cytokines and inhibition of PMCA4. Plasma membrane-associated ceramide which is known to be elevated during leishmaniasis, triggered upregulation of PMCA4 via PKCζ activation. Interestingly, immunomodulators attenuated ceramide generation, which resulted into reduced PKCζ activation leading to the decreased PMCA expression in infected macrophages. Therefore, our study elucidated the efficacy of SAG, Ara-LAM, and GA in the reduction of parasite burden in macrophages by suppressing PMCA activation through inhibition of ceramide mediated upregulation of PKCζ.


Assuntos
Antiprotozoários/uso terapêutico , ATPases Transportadoras de Cálcio/sangue , Membrana Celular/enzimologia , Fatores Imunológicos/farmacologia , Leishmania donovani/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Animais , Gluconato de Antimônio e Sódio/farmacologia , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/farmacologia , Cálcio/metabolismo , ATPases Transportadoras de Cálcio/efeitos dos fármacos , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Ceramidas/metabolismo , Meios de Cultura Livres de Soro , Densitometria , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Ácido Glicirrízico/farmacologia , Ácido Glicirrízico/uso terapêutico , Imipramina/farmacologia , Immunoblotting , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/uso terapêutico , Macrófagos/fisiologia , Camundongos , RNA de Protozoário/genética , RNA de Protozoário/isolamento & purificação , RNA Interferente Pequeno/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Reversa , Transfecção
4.
PLoS Negl Trop Dis ; 13(11): e0007788, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31693661

RESUMO

INTRODUCTION: Cutaneous leishmaniasis (CL), endemic in Bolivia, mostly affects poor people in rainforest areas. The current first-line treatment consists of systemic pentavalent antimonials (SPA) for 20 days and is paid for by the Ministry of Health (MoH). Long periods of drug shortages and a lack of safe conditions to deliver treatment are challenges to implementation. Intralesional pentavalent antimonials (ILPA) are an alternative to SPA. This study aims to compare the cost of ILPA and SPA, and to estimate the health and economic impacts of changing the first-line treatment for CL in a Bolivian endemic area. METHODS: The cost-per-patient treated was estimated for SPA and ILPA from the perspectives of the MoH and society. The quantity and unit costs of medications, staff time, transportation and loss of production were obtained through a health facility survey (N = 12), official documents and key informants. A one-way sensitivity analysis was conducted on key parameters to evaluate the robustness of the results. The annual number of patients treated and the budget impact of switching to ILPA as the first-line treatment were estimated under different scenarios of increasing treatment utilization. Costs were reported in 2017 international dollars (1 INT$ = 3.10 BOB). RESULTS: Treating CL using ILPA was associated with a cost-saving of $248 per-patient-treated from the MoH perspective, and $688 per-patient-treated from the societal perspective. Switching first-line treatment to ILPA while maintaining the current budget would allow two-and-a-half times the current number of patients to be treated. ILPA remained cost-saving compared to SPA in the sensitivity analysis. CONCLUSIONS: The results of this study support a shift to ILPA as the first-line treatment for CL in Bolivia and possibly in other South American countries.


Assuntos
Antiprotozoários/economia , Orçamentos , Redução de Custos , Leishmaniose Cutânea/tratamento farmacológico , Gluconato de Antimônio e Sódio/economia , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Bolívia , Análise Custo-Benefício , Custos de Medicamentos , Custos de Cuidados de Saúde , Humanos , Antimoniato de Meglumina/economia , Antimoniato de Meglumina/uso terapêutico
5.
Am J Trop Med Hyg ; 101(5): 1111-1113, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31516113

RESUMO

Cutaneous leishmaniasis (CL) is a major health problem worldwide. Although CL is a common disease among children, treatment regimens for the pediatric age group are based on extrapolation of efficacy data in adults. The present study aimed to evaluate the treatment outcome of CL in preschool-age children and the factors influencing the outcome. Two hundred ninety-four children were diagnosed with CL between December 2018 and March 2019 in Sinjar Province, Iraq. All patients were treated with intralesional injections of sodium stibogluconate and followed up for 3 months after the completion of treatment. The treatment success rate was 99% (291/294). A statistically significant association was found between the number of doses per lesion and the number of lesions (P = 0.002; CI = 0.066-0.2875). No association was found between the number of lesions, age, gender, or the presence of livestock and the treatment outcome. In conclusion, treatment success rate was high with the use of intralesional injection of sodium stibogluconate. A significant association was found between the number of lesions and the number of doses. Further studies are required to assess the treatment outcome indicators, including the genotype of leishmania.


Assuntos
Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/epidemiologia , Pré-Escolar , Feminino , Humanos , Iraque/epidemiologia , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/patologia , Masculino
6.
Exp Parasitol ; 204: 107728, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31348915

RESUMO

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.


Assuntos
Anti-Helmínticos/uso terapêutico , Antiprotozoários/uso terapêutico , Comorbidade , Leishmania major/patogenicidade , Leishmaniose Cutânea/complicações , Esquistossomose mansoni/complicações , Análise de Variância , Animais , Anti-Helmínticos/administração & dosagem , Gluconato de Antimônio e Sódio/administração & dosagem , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/administração & dosagem , Quimiocina CCL3/sangue , Modelos Animais de Doenças , Quimioterapia Combinada , Interferon gama/sangue , Leishmania major/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/patologia , Fígado/parasitologia , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Praziquantel/administração & dosagem , Praziquantel/uso terapêutico , Schistosoma mansoni/efeitos dos fármacos , Schistosoma mansoni/patogenicidade , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/patologia
8.
Trop Doct ; 49(2): 141-143, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30602348

RESUMO

Cutaneous leishmaniasis (CL) is a parasitic disease which has a biphasic life cycle; infection by promastigotes from the sandfly reaches a wound where it is phagocytosed by macrophages, producing the amastigote (the Leishmania donovani body) in the host. A protozoan parasite transmitted by the phlebotomous sandfly causes human leishmaniasis. Cutaneous forms include classical cutaneous, mucocutaneous and post-kala-azar dermal leishmaniasis. It affects c. 300 million individuals in more than 90 nations around the globe. The cutaneous form in the Old World is caused at low altitudes mainly by L. major (which has an animal reservoir, rodents such as mouse) and in swampy regions and high altitudes by L. tropica (which has no animal reservoir). L. aethiopica and L. major lead to disseminated ulcers in Saudi Arabia, Yemen, Iraq, Iran, Pakistan, India, Tunisia, Sudan and Ethiopia, whose main electrophoretic isozyme pattern Zymodeme in Saudi Arabia is LON-4.


Assuntos
Pavilhão Auricular/parasitologia , Leishmania donovani/isolamento & purificação , Leishmaniose Cutânea/diagnóstico , Úlcera Cutânea/diagnóstico , Adulto , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Pavilhão Auricular/patologia , Humanos , Leishmania donovani/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Masculino , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/parasitologia , Úlcera Cutânea/patologia , Resultado do Tratamento
9.
BMC Genomics ; 19(1): 843, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30486770

RESUMO

BACKGROUND: Leishmaniasis is a neglected tropical disease with diverse clinical phenotypes, determined by parasite, host and vector interactions. Despite the advances in molecular biology and the availability of more Leishmania genome references in recent years, the association between parasite species and distinct clinical phenotypes remains poorly understood. We present a genomic comparison of an atypical variant of Leishmania donovani from a South Asian focus, where it mostly causes cutaneous form of leishmaniasis. RESULTS: Clinical isolates from six cutaneous leishmaniasis patients (CL-SL); 2 of whom were poor responders to antimony (CL-PR), and two visceral leishmaniasis patients (VL-SL) were sequenced on an Illumina MiSeq platform. Chromosome aneuploidy was observed in both groups but was more frequent in CL-SL. 248 genes differed by 2 fold or more in copy number among the two groups. Genes involved in amino acid use (LdBPK_271940) and energy metabolism (LdBPK_271950), predominated the VL-SL group with the same distribution pattern reflected in gene tandem arrays. Genes encoding amastins were present in higher copy numbers in VL-SL and CL-PR as well as being among predicted pseudogenes in CL-SL. Both chromosome and SNP profiles showed CL-SL and VL-SL to form two distinct groups. While expected heterozygosity was much higher in VL-SL, SNP allele frequency patterns did not suggest potential recent recombination breakpoints. The SNP/indel profile obtained using the more recently generated PacBio sequence did not vary markedly from that based on the standard LdBPK282A1 reference. Several genes previously associated with resistance to antimonials were observed in higher copy numbers in the analysis of CL-PR. H-locus amplification was seen in one cutaneous isolate which however did not belong to the CL-PR group. CONCLUSIONS: The data presented suggests that intra species variations at chromosome and gene level are more likely to influence differences in tropism as well as response to treatment, and contributes to greater understanding of parasite molecular mechanisms underpinning these differences. These findings should be substantiated with a larger sample number and expression/functional studies.


Assuntos
Genoma , Leishmania donovani/genética , Leishmania donovani/patogenicidade , Aneuploidia , Gluconato de Antimônio e Sódio/farmacologia , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Sequência de Bases , Cromossomos/genética , Dosagem de Genes , Ontologia Genética , Heterozigoto , Homozigoto , Humanos , Mutação INDEL/genética , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/isolamento & purificação , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Fases de Leitura Aberta/genética , Filogenia , Polimorfismo de Nucleotídeo Único/genética , Virulência/efeitos dos fármacos , Virulência/genética
10.
Infect Dis Poverty ; 7(1): 108, 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30340519

RESUMO

BACKGROUND: Ethiopia has the highest number of visceral leishmaniasis (VL) cases after Sudan in Sub-Saharan Africa. However, there was lack of comprehensive data on VL treatment outcome despite the huge burden of the diseases in the country. Hence, we aimed to perform a systematic review and meta-analysis on this topic to obtain stronger evidence on treatment outcomes of VL from the existing literature in Ethiopia. METHODS: The Cochrane guidelines to conduct meta-analysis following the Preferred Reporting Items for Systematic review and Meta-Analysis statement was used to conduct a computerized systematic search of the PubMed, Google Scholar, and ScienceDirect databases. Random effects model was used to combine studies showing heterogeneity of Cochrane Q P < 0.10 and I2 > 50. Treatment outcomes were assessed at end of treatment and at 6 months follow-up. Subgroup analyses were performed on treatment outcomes based on the different antileishmanial treatment options and patients' HIV status. RESULTS: Fifteen studies were included in the final analyses. At end of treatment, an overall treatment success rate of 82.6% was noticed. At 6 months follow-up, the overall treatment success rate was 72.2%. For patients treated with sodium stibogluconate (SSG), the treatment success rates at the end of treatment and at six-month follow-up were 81.5% and 80.7%, respectively. Multiple doses of liposomal-amphotericin B (L-AMB) had treatment success rates of 96.7 and 71-100% at the end of treatment and at 6 months follow-up, respectively. The combination of SSG with paromomycin (PM) gave treatment success rates of up to 90.1% at the end of treatment. HIV-infected individuals were found to have a higher mortality (odds ratio = 4.77, 95% CI: 1.30-17.43, P = 0.009) rate at 6 months follow-up. CONCLUSIONS: SSG alone has shown lower treatment efficacy in the management of VL when compared to combination of SSG with PM and multiple doses of L-AMB. The combination of SSG with PM gave good treatment success rates with shorter duration of treatment. Hence, the combination of SSG with PM should be used preferentially over SSG monotherapy. Multiple doses of L-AMB showed great efficacy especially among patients with complications, severe disease, HIV co-infection, and intolerance to the adverse effects of antimonials. HIV-infected individuals had a worse prognosis than their HIV-negative counterparts.


Assuntos
Leishmaniose Visceral/epidemiologia , Gluconato de Antimônio e Sódio/farmacologia , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Coinfecção , Feminino , Infecções por HIV , Humanos , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/mortalidade , Leishmaniose Visceral/parasitologia , Masculino , Razão de Chances , Resultado do Tratamento
11.
Int Immunopharmacol ; 64: 372-385, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30245348

RESUMO

The current treatment approach for leishmaniasis has been questioned in terms of development of the resistance and life threatening side-effects. The utility of the drug can only be confirmed by inspecting its safety window along with its impact against different strains of parasite including the resistant ones. The aim of this study was to evaluate the therapeutic effects of a flavonoid, rutin (RTN) against sodium stibogluconate (SSG) sensitive (S-) and resistant (R-) strain of L. donovani. RTN exhibited its anti-promastigote activity via arresting the cells at sub G0/G1 phase. Further RTN resulted in decline of splenic parasite burden. The parasiticidal activity was associated with the elicitation of cell-mediated immune response in terms of increased DTH response, augmented levels of T cells (CD4+, CD8+), Th1 cytokines, NO and ROS. RTN also up-regulated the expression of NF-ĸB and iNOS gene in S- as well as R- strain infected mice. Where no therapeutic effect of SSG was seen in the R-strain infected mice, the RTN treatment was able to control the disease in even R-strain infected mice. Moreover RTN was found to be devoid of any hepatic or renal toxicity. RTN could control the infection and it even had the capacity to counteract the resistant parasite by restoring the ability of host to produce protective immune response and microbicidal NO via up-regulating NF-ĸB and iNOS gene. This finding elucidates RTN to be a strong candidate in the antileishmanial drug pipeline not only against the sensitive but resistant strains also.


Assuntos
Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmania donovani/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Rutina/uso terapêutico , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Citocinas/análise , Resistência a Medicamentos , Hipersensibilidade Tardia/etiologia , Leishmania donovani/isolamento & purificação , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/patologia , Camundongos , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Baço/imunologia
12.
Am J Trop Med Hyg ; 99(2): 327-330, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29869609

RESUMO

Mucosal leishmaniasis (ML) is associated with progressive tissue destruction and granuloma formation, often after a considerable period of latency from an initial cutaneous infection. We report a case of recurrent epistaxis of 3 years duration and nasopharyngeal obstruction in a woman with treated cutaneous leishmaniasis nearly 30 years before and with no further exposure to Leishmania. Computed tomography revealed nasal septal perforation and histopathology demonstrated chronic inflammation. Microscopy was negative for amastigotes, but molecular testing of nasal mucosa biopsy detected Leishmania (Viannia) braziliensis. The patient underwent 28 days of treatment with IV sodium stibogluconate and her symptoms improved significantly. Sixteen months after treatment, she continues to have episodic epistaxis and detectable parasite load in her nasal lesion. Although ML is known to take years to decades to develop, there are few reported cases in the literature of such a long latency period. This report highlights the importance of considering ML in the differential diagnosis of chronic epistaxis in countries where leishmaniasis is endemic or in immigrants from these countries, even when presentation occurs decades after leaving an endemic region.


Assuntos
Leishmaniose Mucocutânea/complicações , Leishmaniose Mucocutânea/diagnóstico , Mucosa Nasal/parasitologia , Perfuração do Septo Nasal/parasitologia , Adulto , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Diagnóstico Diferencial , Epistaxe/parasitologia , Feminino , Humanos , Inflamação , Leishmania braziliensis/genética , Leishmania braziliensis/isolamento & purificação , Leishmaniose Mucocutânea/tratamento farmacológico , Perfuração do Septo Nasal/diagnóstico por imagem , Septo Nasal/diagnóstico por imagem , Septo Nasal/patologia , Carga Parasitária , Peru , Fatores de Tempo , Tomografia Computadorizada por Raios X
13.
Infect Dis Poverty ; 7(1): 12, 2018 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-29444705

RESUMO

BACKGROUND: The present health economic evaluation in Afghanistan aims to support public health decision makers and health care managers to allocate resources efficiently to appropriate treatments for cutaneous leishmaniasis (CL) elicited by Leishmania tropica or Leishmania major. METHODS: A decision tree was used to analyse the cost and the effectiveness of two wound care regimens versus intra-lesional antimony in CL patients in Afghanistan. Costs were collected from a societal perspective. Effectiveness was measured in wound free days. The incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (NMB) were calculated. The model was parameterized with baseline parameters, sensitivity ranges, and parameter distributions. Finally, the model was simulated and results were evaluated with deterministic and probability sensitivity analyses. Final outcomes were the efficiency of the regimens and a budget impact analysis in the context of Afghanistan. RESULTS: Average costs per patients were US$ 11 (SE = 0.016) (Group I: Intra-dermal Sodium Stibogluconate [IL SSG]), US$ 16 (SE = 7.58) (Group II: Electro-thermo-debridement [ETD] + Moist wound treatment [MWT]) and US$ 25 (SE = 0.48) (Group III: MWT) in patients with a single chronic CL ulcer. From a societal perspective the budget impact analysis shows that the regimens' drug costs are lower than indirect disease cost. Average effectiveness in wound free days are 177 (SE = 0.36) in Group II, 147 (SE = 0.33) in Group III, and 129 (SE = 0.27) in Group I. The ICER of Group II versus Group I was US$ 0.09 and Group III versus Group I US$ 0.77, which is very cost-effective with a willingness-to-pay threshold of US$ 2 per wound free day. Within a Monte-Carlo probabilistic sensitivity analysis Group II was cost-effective in 80% of the cases starting at a willingness-to-pay of 80 cent per wound free day. CONCLUSIONS: Group II provided the most cost-effective treatment. The non-treatment alternative is not an option in the management of chronic CL ulcers. MWT of Group III should at least be practiced. The cost-effectiveness of Group III depends on the number of dressings necessary until complete wound closure.


Assuntos
Análise Custo-Benefício , Leishmaniose Cutânea , Modelos Estatísticos , Cicatrização , Afeganistão/epidemiologia , Gluconato de Antimônio e Sódio/economia , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/economia , Antiprotozoários/uso terapêutico , Desbridamento/economia , Árvores de Decisões , Humanos , Leishmaniose Cutânea/economia , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/terapia , Método de Monte Carlo , Ensaios Clínicos Controlados Aleatórios como Assunto , Úlcera/economia , Úlcera/epidemiologia , Úlcera/terapia
14.
BMC Res Notes ; 10(1): 698, 2017 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-29208030

RESUMO

BACKGROUND: Conventional targeted leishmanicidal chemotherapy has persistently remained prohibitive for most economically deprived communities due to costs, associated time to accessing health services and duration for successful treatment programme. Alternatives are bound to be incorporated in rational management of leishmaniasis by choice or default due to accessibility and cultural beliefs. Therefore, there is need to rigorously investigate and appraise the activity of medicinal compounds that may have anti-leishmanicidal activity especially in the context of products that are already being utilized by the populations for other ailments but have limited information on their therapeutic value and possible cytoxicity. Hence, the study examined both in vivo and in vitro response of L. major infection to Tephrosia vogelii extracts in BALB/c mice as the mouse model. METHODS: A comparative study design was applied for the in vivo and in vitro assays of the extract with Pentostam (GlaxoSmithKline, UK) and Amphotericin B [Fungizone™, X-Gen Pharmaceuticals (US)] as standard drugs. RESULTS: In BALB/c mice where the chemotherapeutic extract was administered intraperitoneally, there was significantly (p < 0.05) larger reduction in lesion size and optimal control of parasite burden than those treated orally. However, standard drugs showed better activity. Tephrosia vogelii had 50% inhibitory concentration (IC50) and IC90 of 12 and 68.5 µg/ml respectively, while the standard drugs had IC50 and IC90 of 5.5 and 18 µg/ml for Pentostam and 7.8 and 25.5 µg/ml for Amphotericin B in that order. In the amastigote assay, the infection rates decreased with increase in chemotherapeutic concentration. The multiplication indices for L. major amastigotes in macrophages treated with 200 µg/ml of the standard drugs and extract were significantly different (p < 0.05). 200 µg/ml of T. vogelii extract showed a multiplication index of 20.57, 5.65% for Amphotericin B and 9.56% for Pentostam. There was also significant difference (p < 0.05) in levels of Nitric oxide produced in the macrophages. CONCLUSIONS: The findings demonstrated that T. vogelii extract has anti-leishmanial activity and further assays should be done to ascertain the active compounds responsible for anti-leishmanial activity.


Assuntos
Modelos Animais de Doenças , Leishmaniose Cutânea/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Tephrosia/química , Anfotericina B/uso terapêutico , Animais , Gluconato de Antimônio e Sódio/uso terapêutico , Peso Corporal/efeitos dos fármacos , Concentração Inibidora 50 , Fígado/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/biossíntese , Tamanho do Órgão/efeitos dos fármacos , Baço/efeitos dos fármacos
15.
PLoS One ; 12(9): e0184777, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28926630

RESUMO

BACKGROUND: The mainstays of cutaneous leishmaniasis (CL) treatment, in several world regions, are pentavalent antimony (Sbv) compounds administered parenterally, despite their recognized toxicity, which requires frequent laboratory monitoring and complicates their use in areas with scarce infrastructure. As result of these drawbacks, the WHO Expert Committee on leishmaniasis has expanded the recommendations for the use of local therapies, including Sbv intralesional infiltration (IL-Sbv), as CL therapy alternatives even in the New World. However, the efficacy of these approaches has never been compiled. The aim of this study was to critically and systematically assess the efficacy of IL-Sbv for CL treatment. METHODOLOGY: The PRISMA guidelines for systematic reviews and the Cochrane manual were followed. The sources used were the MEDLINE and LILACS databases and the International Clinical Trials Registry Platform of the World Health Organization. The outcome of interest was a clinical cure, defined as complete re-epithelialization of all lesions. The IL-Sbv pooled cure rate was estimated for several subgroups and direct comparisons were performed when possible. RESULTS: Thirty nine articles (40 studies) involving 5679 patients treated with IL-Sbv infiltration were included. In direct comparison, only three studies involving 229 patients compared IL-Sbv infiltration versus placebo and no difference was observed (OR: 1,9; 95%IC 0,93 to 3,82) based on cure rate 69.6% (95%CI 17.6-96.1%) and 83,2% (95%CI 66-92.7%) for placebo and IL-Sbv, respectively. In an alternative and non-comparative analysis, gathering all study arms using the intervention, the pooled IL-Sbv efficacy rate was 75% (95%CI 68-81%). In the Old World, the observed overall IL-Sbv efficacy rate was 75% (95%CI 66-82%), and the cure rates were significantly higher with sodium stibogluconate (SSG) than with meglumine antimoniate (MA): 83% (95%CI 75-90%) versus 68% (95%CI 54-79%), p = 0.03. Studies directly comparing IL-Sbv with topical 15% paromomycin ointment, IL hypertonic saline, radiofrequency-induced heat therapy, topical trichloroacetic acid and cryotherapy showed no significant difference in efficacy between the interventions. The analyses suggested a higher efficacy of IL-Sbv combined with cryotherapy (81.8%, 95%IC 62.4-92.4%) when compared with IL-Sbv alone (53.3%, 95%IC 46.1-66%), OR: 3.14 (95%CI 1.1-8.9), p = 0.03. In the New World, the global IL-Sbv efficacy was 77%(95%CI 66-85%). In contrast with the Old World, a significant difference favoring MA in relation to SSG was observed: 61% (95%CI 49-73%) versus 82% (95%CI 70-89%).By comparing IL infiltration schedules, it was determined that patients submitted to IL-Sbv treatments longer than 14 days had higher cure rates. CONCLUSIONS: Despite the high heterogeneity and low methodological quality of studies, an indirect comparison shows that the antimony infiltration efficacy rate is similar to that reported for antimony systemic use. The evidence gathered thus far is insufficient to identify the ideal IL therapeutic regime or estimate the rates of adverse events and mucosal late complications.


Assuntos
Antimônio/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Antimônio/química , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/química , Crioterapia , Bases de Dados Factuais , Humanos , Injeções Intralesionais , Leishmaniose Cutânea/patologia , Meglumina/uso terapêutico , Antimoniato de Meglumina , Compostos Organometálicos/uso terapêutico , Resultado do Tratamento
17.
Am J Trop Med Hyg ; 97(4): 1120-1126, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28820681

RESUMO

Leishmania donovani causes cutaneous leishmaniasis (CL) in Sri Lanka. Standard treatment is multiple, painful doses of intralesional sodium stibogluconate (IL-SSG). Treatment failures are increasingly reported, hence the need to investigate alternatives. Efficacy, safety, and cost-effectiveness of thermotherapy were assessed for the first time for L. donovani CL. A single blinded noninferiority randomized controlled trial was conducted on new laboratory-confirmed CL patients with single lesions (N = 213). Selected patients were randomly assigned to 1) test group (N = 98; single session of radiofrequency-induced heat therapy (RFHT) given at 50°C for 30 seconds) and 2) control group (N = 115; 1-3 mL IL-SSG given weekly, until cure/10 doses). Patients were followed-up fortnightly for 12 weeks to assess clinical cure. Cost of treatment was assessed using scenario building technique. Cure rates by 8, 10, and 12 weeks in RFHT group were 46.5%, 56.5%, and 65.9% as opposed to 28%, 40.8%, and 59.4% in IL-SSG group, with no major adverse events. Cure rate by RFHT was significantly higher at 8 weeks (P = 0.009, odds ratio [OR]: 2.236, confidence interval [CI]: 1.217-4.108) and 10 weeks (P = 0.035, OR: 1.881, CI: 1.044-3.388), but comparable thereafter. Cost of RFHT was 7 times less (USD = 1.54/patient) than IL-SSG (USD = 11.09/patient). A single application of RFHT is safe, cost-effective, and convenient, compared with multiple doses of IL-SSG in the treatment of L. donovani CL. Therefore, RFHT would be considered noninferior as per trial outcome when compared with standard IL-SSG therapy with multiple benefits for the patient and the national health care system.


Assuntos
Hipertermia Induzida , Leishmania donovani , Leishmaniose Cutânea/terapia , Leishmaniose Visceral/terapia , Adolescente , Adulto , Gluconato de Antimônio e Sódio/administração & dosagem , Gluconato de Antimônio e Sódio/uso terapêutico , Criança , Feminino , Humanos , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Leishmaniose Visceral/parasitologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Am J Trop Med Hyg ; 97(5): 1503-1507, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28820714

RESUMO

This study describes the epidemiological and clinical characteristics of leishmaniasis and the pharmacological treatment of this disease in the municipality of Pueblo Rico, Risaralda, between January 2010 and December 2014. An observational study was conducted using information from the clinical records and epidemiological reports of patients diagnosed and confirmed with leishmaniasis of any age and sex, including sociodemographic, clinical, and pharmacological variables of the therapy received. Univariate and bivariate analyses were performed. A total of 539 cases of leishmaniasis were confirmed, with 29.5% occurring in children under 5 years of age. The median age was 10 years, with predominance in males (55.5%). The indigenous Emberá (aboriginal Americans) were the most affected (50.8%), and 93.3% of cases occurred in people living in scattered rural areas. All lesions corresponded to cutaneous leishmaniasis, of which 251 patients had compromise of the upper limbs (46.6%), 221 of the face (41.0%), and 139 of the lower limbs (25.8%). Pentavalent antimony salts (n-methyl glucamine and sodium stibogluconate) were prescribed in 77.6% (N = 418) of the cases; miltefosine was the second most frequently prescribed medication (21.5%, N = 116). The inhabitants of rural areas and the indigenous communities are at a higher risk of acquiring the infection, particularly among infants, which highlights the importance of the biological, social, and demographic factors involved in the disease. There is a need to seek effective public health actions and further research this disease.


Assuntos
Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/epidemiologia , Adolescente , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Criança , Pré-Escolar , Colômbia/epidemiologia , Feminino , Humanos , Masculino , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapêutico , Prevalência , Estudos Retrospectivos , Fatores Socioeconômicos , População Urbana , Adulto Jovem
19.
Trop Med Int Health ; 22(8): 1037-1042, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28594453

RESUMO

OBJECTIVE: To assess the rate of default from treatment in the visceral leishmaniasis (VL) elimination programme and to identify risk factors and its underlying causes. METHODS: Case-control study conducted between December 2009 and June 2012 in three primary health centres (PHCs) of Muzaffarpur district, India. Patients who defaulted from treatment from the PHCs were considered as 'cases' and those who completed their treatment as 'controls'. Two controls were included in the study for each case. Respondents' opinion and satisfaction with the services provided at the PHCs were also elicited. Logistic regression was performed to assess the contribution of sociodemographic variables on patient status, and a discriminant analysis was used (after decomposing the original data) to identify factors that can predict the patient status as defaulter or not, based on factor scores of the components as predictor variables. RESULTS: During the study period, 16.3% (89/544) of patients defaulted; 87 cases and 188 controls were interviewed through a semistructured questionnaire. Women tended to be more at risk for default (OR, 1.6, 95% CI (0.9 -2.9). Treatment received was miltefosine in 55.6% and sodium stibogluconate (SSG) in 44.4%. Most (86%) defaulters completed their treatment at other healthcare facilities; 70% of them preferred non-governmental institutions. Most cited reasons for default were seeking a second opinion for VL treatment and preferring to be treated in specialised VL centres. Discriminant analysis showed only one significant predictor: dissatisfaction with the medical care received in PHCs. CONCLUSION: Efforts are needed to enhance the quality of VL care at PHC level, which will be beneficial in increasing treatment completion rates.


Assuntos
Instalações de Saúde , Leishmaniose Visceral , Programas Nacionais de Saúde , Satisfação do Paciente , Atenção Primária à Saúde , Adulto , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Feminino , Humanos , Índia , Leishmaniose Visceral/tratamento farmacológico , Masculino , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapêutico , Setor Privado , Setor Público , Especialização , Adulto Jovem
20.
Parasite Immunol ; 39(6)2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28370072

RESUMO

Visceral leishmaniasis (VL) in Sudan caused by Leishmania donovani is fatal in susceptible individuals if untreated. Treatment with sodium stibogluconate (SSG) leads to post-kala-azar dermal leishmaniasis (PKDL) in 58% of patients. Here, Affymetrix microarrays were used to identify genes differentially expressed in lymph nodes (N=9 paired samples) pre- and post-treatment with SSG. Using the Bioconductor package limma, 438 genes from 28 869 post-quality-control probe sets were differentially expressed (Pnominal ≤.02) post- vs pretreatment. Canonical pathway analysis using Ingenuity Pathway Analysis™ identified "role of nuclear factor of activated T-cell in regulation of immune response" (Pnominal =1.35×10-5 ; PBH-adjusted =4.79×10-3 ), "B-cell development" (Pnominal =2.04×10-4 ; PBH-adjusted =.024), "Fcγ receptor-mediated phagocytosis in macrophages and monocytes" (Pnominal =2.04×10-4 ; PBH-adjusted =.024) and "OX40 signalling" (Pnominal =2.82×10-4 ; PBH-adjusted =.025) as pathways differentially regulated post- vs pretreatment. Major network hub genes included TP53, FN1, MYC, BCL2, JUN, SYK, RUNX2, MMP1 and ACTA2. Top endogenous upstream regulators included IL-7 (P=2.28×10-6 ), TNF (P=4.26×10-6 ), Amyloid Precursor Protein (P=4.23×10-5 ) and SPI1/PI.1 (P=1.17×10-7 ). Top predicted chemical drug regulators included the flavonoid genistein (P=4.56×10-7 ) and the quinoline alkaloid camptothecin (P=5.14×10-5 ). These results contribute to our understanding of immunopathology associated with VL and response to SSG treatment. Further replication could identify novel therapeutic strategies that improve on SSG treatment and reduce the likelihood of progression to PKDL.


Assuntos
Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmania donovani , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/genética , Transcriptoma/efeitos dos fármacos , Adolescente , Criança , Feminino , Humanos , Leishmaniose Cutânea/imunologia , Leishmaniose Visceral/imunologia , Masculino , Sudão , Adulto Jovem
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