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1.
PLoS Negl Trop Dis ; 14(12): e0008919, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33382717

RESUMO

BACKGROUND: Ghana is endemic for some neglected tropical diseases (NTDs) including schistosomiasis, onchocerciasis and lymphatic filariasis. The major intervention for these diseases is mass drug administration of a few repeatedly recycled drugs which is a cause for major concern due to reduced efficacy of the drugs and the emergence of drug resistance. Evidently, new treatments are needed urgently. Medicinal plants, on the other hand, have a reputable history as important sources of potent therapeutic agents in the treatment of various diseases among African populations, Ghana inclusively, and provide very useful starting points for the discovery of much-needed new or alternative drugs. METHODOLOGY/PRINCIPAL FINDINGS: In this study, extracts of fifteen traditional medicines used for treating various NTDs in local communities were screened in vitro for efficacy against schistosomiasis, onchocerciasis and African trypanosomiasis. Two extracts, NTD-B4-DCM and NTD-B7-DCM, prepared from traditional medicines used to treat schistosomiasis, displayed the highest activity (IC50 = 30.5 µg/mL and 30.8 µg/mL, respectively) against Schistosoma mansoni adult worms. NTD-B2-DCM, also obtained from an antischistosomal remedy, was the most active against female and male adult Onchocera ochengi worms (IC50 = 76.2 µg/mL and 76.7 µg/mL, respectively). Antitrypanosomal assay of the extracts against Trypanosoma brucei brucei gave the most promising results (IC50 = 5.63 µg/mL to 18.71 µg/mL). Incidentally, NTD-B4-DCM and NTD-B2-DCM, also exhibited the greatest antitrypanosomal activities (IC50 = 5.63 µg/mL and 7.12 µg/mL, respectively). Following the favourable outcome of the antitrypanosomal screening, this assay was selected for bioactivity-guided fractionation. NTD-B4-DCM, the most active extract, was fractionated and subsequent isolation of bioactive constituents led to an eupatoriochromene-rich oil (42.6%) which was 1.3-fold (IC50 <0.0977 µg/mL) more active than the standard antitrypanosomal drug, diminazene aceturate (IC50 = 0.13 µg/mL). CONCLUSION/SIGNIFICANCE: These findings justify the use of traditional medicines and demonstrate their prospects towards NTDs drug discovery.


Assuntos
Filaricidas/farmacologia , Onchocerca/efeitos dos fármacos , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Animais , Gana , Medicina Tradicional Africana , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/parasitologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química
3.
PLoS Negl Trop Dis ; 14(9): e0008353, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32970675

RESUMO

Diseases caused by pathogenic free-living amoebae include primary amoebic meningoencephalitis (Naegleria fowleri), granulomatous amoebic encephalitis (Acanthamoeba spp.), Acanthamoeba keratitis, and Balamuthia amoebic encephalitis (Balamuthia mandrillaris). Each of these are difficult to treat and have high morbidity and mortality rates due to lack of effective therapeutics. Since repurposing drugs is an ideal strategy for orphan diseases, we conducted a high throughput phenotypic screen of 12,000 compounds from the Calibr ReFRAME library. We discovered a total of 58 potent inhibitors (IC50 <1 µM) against N. fowleri (n = 19), A. castellanii (n = 12), and B. mandrillaris (n = 27) plus an additional 90 micromolar inhibitors. Of these, 113 inhibitors have never been reported to have activity against Naegleria, Acanthamoeba or Balamuthia. Rapid onset of action is important for new anti-amoeba drugs and we identified 19 compounds that inhibit N. fowleri in vitro within 24 hours (halofuginone, NVP-HSP990, fumagillin, bardoxolone, belaronib, and BPH-942, solithromycin, nitracrine, quisinostat, pabinostat, pracinostat, dacinostat, fimepinostat, sanguinarium, radicicol, acriflavine, REP3132, BC-3205 and PF-4287881). These compounds inhibit N. fowleri in vitro faster than any of the drugs currently used for chemotherapy. The results of these studies demonstrate the utility of phenotypic screens for discovery of new drugs for pathogenic free-living amoebae, including Acanthamoeba for the first time. Given that many of the repurposed drugs have known mechanisms of action, these compounds can be used to validate new targets for structure-based drug design.


Assuntos
Amebíase/tratamento farmacológico , Amebicidas/farmacologia , Reposicionamento de Medicamentos/métodos , Ensaios de Triagem em Larga Escala/métodos , Acanthamoeba/efeitos dos fármacos , Balamuthia mandrillaris/efeitos dos fármacos , Bases de Dados de Produtos Farmacêuticos , Naegleria fowleri/efeitos dos fármacos , Doenças Negligenciadas/tratamento farmacológico , Bibliotecas de Moléculas Pequenas
4.
PLoS Negl Trop Dis ; 14(9): e0008588, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32925917

RESUMO

BACKGROUND: Significant efforts to control human African trypanosomiasis (HAT) over the two past decades have resulted in drastic decrease of its prevalence in Côte d'Ivoire. In this context, passive surveillance, integrated in the national health system and based on clinical suspicion, was reinforced. We describe here the health-seeking pathway of a girl who was the first HAT patient diagnosed through this strategy in August 2017. METHODS: After definitive diagnosis of this patient, epidemiological investigations were carried out into the clinical evolution and the health and therapeutic itinerary of the patient before diagnosis. RESULTS: At the time of diagnosis, the patient was positive in both serological and molecular tests and trypanosomes were detected in blood and cerebrospinal fluid. She suffered from important neurological disorders. The first disease symptoms had appeared three years earlier, and the patient had visited several public and private peripheral health care centres and hospitals in different cities. The failure to diagnose HAT for such a long time caused significant health deterioration and was an important financial burden for the family. CONCLUSION: This description illustrates the complexity of detecting the last HAT cases due to complex diagnosis and the progressive disinterest and unawareness by both health professionals and the population. It confirms the need of implementing passive surveillance in combination with continued sensitization and health staff training.


Assuntos
Diagnóstico Tardio/economia , Doenças Negligenciadas/diagnóstico , Doenças Negligenciadas/tratamento farmacológico , Tripanossomíase Africana/diagnóstico , Tripanossomíase Africana/tratamento farmacológico , Sangue/parasitologia , Líquido Cefalorraquidiano/parasitologia , Criança , Indicadores de Doenças Crônicas , Costa do Marfim/epidemiologia , Feminino , Humanos , Doenças Negligenciadas/parasitologia , Administração dos Cuidados ao Paciente/economia , Trypanosoma brucei gambiense/isolamento & purificação , Tripanossomíase Africana/parasitologia
6.
Exp Parasitol ; 216: 107940, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32562606

RESUMO

Therapeutic options for the treatment of leishmaniasis are insufficient and need improvements owing to their low efficiency and high toxicity as well as the emergence of resistant strains. The limited number of new drugs for neglected diseases and lack of innovation in your development are still challenges. In this context, the process of discovery and development of biological assays play a pivotal role for the identification of bioactive compounds. The assays currently used for screening of drugs with cytotoxic activity against Leishmania parasites, include different processes that utilize intact parasite (free or intracellular) or specific enzymes of metabolism as a target cell. These assays allow the screening of large numbers of samples followed by more detailed secondary confirmatory assays to confirm the observed activity and assess their toxicity. In the present study, we described the development of a new functional and more complete assay that enables simultaneous assessment of potential anti-Leishmania compounds through evaluation of internalization of fluorescein-labeled L. braziliensis promastigotes by human peripheral blood monocytes and their cytotoxicity by flow cytometry. We standardized the conditions for parasite labeling to achieve better phagocytosis analysis by setting the ratio of number of parasites per cell as 1 to 2, at incubation time of 6h. The cytotoxicity assessment was performed by the quantification of cells undergoing early/late apoptosis and necrosis using a double labelling platform employing 7AAD for late apoptosis and necrosis analysis and Annexin-V for early apoptosis evaluation. Hemolysis analysis was an additional parameter to test cytotoxicity. Two drugs used on clinic (Amphotericin B and Glucantime®) were used to validate the proposed methodology, and the assay was able to detect their known leishmanicidal activity and immunotoxicity properties. This new predictive assay will contribute to the development of translational medicine strategies in drug discovery for neglected diseases such as leishmaniasis.


Assuntos
Alternativas aos Testes com Animais/métodos , Antiprotozoários/toxicidade , Citometria de Fluxo/métodos , Leishmania/efeitos dos fármacos , Doenças Negligenciadas/tratamento farmacológico , Adulto , Anfotericina B/farmacologia , Anfotericina B/toxicidade , Animais , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Fluoresceína-5-Isotiocianato , Corantes Fluorescentes , Humanos , Leishmania braziliensis/efeitos dos fármacos , Leishmaniose/tratamento farmacológico , Leucócitos/efeitos dos fármacos , Leucócitos/parasitologia , Antimoniato de Meglumina/farmacologia , Antimoniato de Meglumina/uso terapêutico , Antimoniato de Meglumina/toxicidade , Microscopia Confocal , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/parasitologia , Fatores de Tempo , Adulto Jovem
7.
Exp Parasitol ; 216: 107943, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32598890

RESUMO

The search for novel therapeutic candidates against animal trypanosomiasis is an ongoing scientific endevour because of the negative impacts of the disease to the African livestock industry. In this study, the in vivo therapeutic potentials of phytol toward Trypanosoma congolense infection and the inhibitory effects on trypanosomal sialidase were investigated. Rats were infected with T. congolense and administered daily oral treatment of 50 and 100 mg/kg BW of phytol. Within the first 10 days of the treatment, no antitrypanosomal activity was recorded but a moderate trypanostatic activity was observed from day 17-day 21 pi. However, at 100 mg/kg BW, phytol demonstrated a significant (p < 0.05) ameliorative potentials toward T. congolense-induced host-associated pathological damages such as anaemia, hepatic and renal damages; and the data was comparable to diminazine aceturate. Moreover, the T. congolense caused a significant (p < 0.05) increase in free serum sialic acid level which was significantly (p < 0.05) prevented in the presence of phytol (100 mg/kg BW). In an in vitro analysis, phytol inhibited partially purified T. congolense sialidase using an uncompetitive inhibition pattern with inhibition binding constant of 261.24 µmol/mL. Subsequently, molecular docking revealed that the compound binds to homology modelled trypanosomal sialidase with a binding free energy of -6.7 kcal/mol which was mediated via a single hydrogen bond while Trp324 and Pro274 were the critical binding residues. We concluded that phytol has moderate trypanostatic activity but with a great potential in mitigating the host-associated cellular damages while the anaemia amelioration was mediated, in part, through the inhibition of sialidase.


Assuntos
Antiprotozoários/uso terapêutico , Inibidores Enzimáticos/farmacologia , Neuraminidase/antagonistas & inibidores , Fitol/uso terapêutico , Trypanosoma congolense/efeitos dos fármacos , Tripanossomíase Africana/veterinária , Animais , Antiprotozoários/farmacologia , Inibidores Enzimáticos/uso terapêutico , Gado , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/veterinária , Neuraminidase/química , Neuraminidase/isolamento & purificação , Fitol/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Trypanosoma congolense/enzimologia , Tripanossomíase Africana/tratamento farmacológico
8.
Am J Trop Med Hyg ; 103(1_Suppl): 5-13, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32400343

RESUMO

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in late 2008 to conduct operational research that would inform practices related to the control and elimination of schistosomiasis. This article traces SCORE's beginnings and underpinnings. These include an emphasis on openness and contributing to the development of a cohesive schistosomiasis control community, building linkages between researchers and national programs, and focusing on answering questions that will help Neglected Tropical Disease program managers to better control and eliminate schistosomiasis. It describes the development and implementation of SCORE's multiple projects. SCORE began by drawing on advice from a broad range of experts by holding wide-ranging meetings that informed the priorities and protocols for SCORE research. SCORE's major efforts included large, multicountry field studies comparing multiple strategies for mass drug administration with praziquantel, assessment of approaches to elimination, evaluation of a point-of-care assay for field mapping Schistosoma mansoni, and increasing the sensitivity of a laboratory-based diagnostic. SCORE also supported studies on morbidity due to schistosomiasis, quantification of vector snails and the detection of schistosome infections in snails, and changes in schistosome population genetics under praziquantel drug pressure. SCORE data and specimens are archived and will remain available for future research. Although much remains to be carried out, our hope is that through the already published articles and SCORE results described in this supplement, we will have provided a body of evidence to assist policy makers in the development of judicious guidelines for the control and elimination of schistosomiasis.


Assuntos
Esquistossomose mansoni , Esquistossomose , Animais , Reservatórios de Doenças , Vetores de Doenças , História do Século XXI , Humanos , Administração Massiva de Medicamentos , Morbidade , Doenças Negligenciadas/diagnóstico , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/prevenção & controle , Parasitologia/história , Praziquantel/uso terapêutico , Prevalência , Schistosoma haematobium , Schistosoma mansoni , Esquistossomose/diagnóstico , Esquistossomose/tratamento farmacológico , Esquistossomose/epidemiologia , Esquistossomose/prevenção & controle , Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/prevenção & controle , Caramujos/parasitologia
9.
Am J Trop Med Hyg ; 103(1_Suppl): 125-134, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32400345

RESUMO

Herein, we summarize what we consider are major contributions resulting from the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) program, including its key findings and key messages from those findings. Briefly, SCORE's key findings are as follows: i) biennial mass drug administration (MDA) with praziquantel can control schistosomiasis to moderate levels of prevalence; ii) MDA alone will not achieve elimination; iii) to attain and sustain control throughout endemic areas, persistent hotspots need to be identified following a minimal number of years of annual MDA and controlled through adaptive strategies; iv) annual MDA is more effective than biennial MDA in high-prevalence areas; v) the current World Health Organization thresholds for decision-making based on the prevalence of heavy infections should be redefined; and vi) point-of-care circulating cathodic antigen urine assays are useful for Schistosoma mansoni mapping in low-to-moderate prevalence areas. The data and specimens collected and curated through SCORE efforts will continue to be critical resource for future research. Besides providing useful information for program managers and revision of guidelines for schistosomiasis control and elimination, SCORE research and outcomes have identified additional questions that need to be answered as the schistosomiasis community continues to implement effective, evidence-based programs. An overarching contribution of SCORE has been increased cohesiveness within the schistosomiasis field-oriented community, thereby fostering new and productive collaborations. Based on SCORE's findings and experiences, we propose new approaches, thresholds, targets, and goals for control and elimination of schistosomiasis, and recommend research and evaluation activities to achieve these targets and goals.


Assuntos
Diretrizes para o Planejamento em Saúde , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose/prevenção & controle , África/epidemiologia , Animais , Anti-Helmínticos/uso terapêutico , Antígenos de Helmintos/imunologia , Biomarcadores/sangue , Criança , Fezes/parasitologia , Glicoproteínas/imunologia , Proteínas de Helminto/imunologia , Humanos , Masculino , Administração Massiva de Medicamentos , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/prevenção & controle , Contagem de Ovos de Parasitas , Praziquantel/uso terapêutico , Prevalência , Saúde Pública , Esquistossomose/diagnóstico , Esquistossomose/tratamento farmacológico , Esquistossomose/epidemiologia , Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/prevenção & controle
10.
Am J Trop Med Hyg ; 103(1_Suppl): 114-124, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32400350

RESUMO

For the past 10 years, the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE), funded by the Bill & Melinda Gates Foundation, has been supporting operational research to provide a stronger evidence base for controlling and moving toward elimination of schistosomiasis. The SCORE portfolio was developed and implemented with engagement from many stakeholders and sectors. Particular efforts were made to include endemic country neglected tropical disease program managers. Examples of the challenges we encountered include the need to balance rigor (e.g., conducting large cluster-randomized trials) with ensuring relevance to real-world settings, allowing for local contexts while standardizing key study aspects, adjusting to evolving technologies, and incorporating changing technologies into multiyear studies. The Schistosomiasis Consortium for Operational Research and Evaluation's findings and data and the collected specimens will continue to be useful in the years to come. Our experiences and lessons learned can benefit both program managers and researchers conducting similar work in the future.


Assuntos
Diretrizes para o Planejamento em Saúde , Esquistossomose/prevenção & controle , África/epidemiologia , Anti-Helmínticos/uso terapêutico , Análise de Dados , Humanos , Administração Massiva de Medicamentos , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/prevenção & controle , Prevalência , Saúde Pública , Esquistossomose/tratamento farmacológico , Esquistossomose/epidemiologia , Resultado do Tratamento , Medicina Tropical/estatística & dados numéricos
11.
Am J Trop Med Hyg ; 103(1_Suppl): 105-113, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32400352

RESUMO

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created to conduct research that could inform programmatic decision-making related to schistosomiasis. SCORE included several large cluster randomized field studies involving mass drug administration (MDA) with praziquantel. The largest of these were studies of gaining or sustaining control of schistosomiasis, which were conducted in five African countries. To enhance relevance for routine practice, the MDA in these studies was coordinated by or closely aligned with national neglected tropical disease (NTD) control programs. The study protocol set minimum targets of at least 90% for coverage among children enrolled in schools and 75% for all school-age children. Over the 4 years of intervention, an estimated 3.5 million treatments were administered to study communities. By year 4, the median village coverage was at or above targets in all studies except that in Mozambique. However, there was often a wide variation behind these summary statistics, and all studies had several villages with very low or high coverage. In studies where coverage was estimated by comparing the number of people treated with the number eligible for treatment, denominator estimation was often problematic. The SCORE experiences in conducting these studies provide lessons for future efforts that attempt to implement strong research designs in real-world contexts. They also have potential applicability to country MDA campaigns against schistosomiasis and other NTDs, most of which are conducted with less logistical and financial support than was available for the SCORE study efforts.


Assuntos
Anti-Helmínticos/uso terapêutico , Administração Massiva de Medicamentos , Esquistossomose/tratamento farmacológico , África , Animais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Moçambique , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/prevenção & controle , Praziquantel/uso terapêutico , Prevalência , Saúde Pública , População Rural , Schistosoma , Esquistossomose/prevenção & controle , Instituições Acadêmicas
12.
PLoS Negl Trop Dis ; 14(4): e0008258, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32310966

RESUMO

Soil-transmitted helminthiases (STH) are one of 17 neglected tropical diseases (NTDs) earmarked for control or elimination by 2020 in the WHO's Roadmap on NTDs. Deworming programs for STH have thus far been focused on treating pre-school and school-aged children; however, there is a growing consensus that to achieve elimination of STH transmission, programs must also target adults, potentially through community-wide mass drug administration (MDA). There is currently a gap in the literature on what components are required to deliver community-wide MDA for STH in order to achieve high intervention reach and uptake. Nested within the TUMIKIA Project, a cluster randomized trial in Kenya evaluating the effectiveness of school-based deworming versus community-wide MDA, we collected qualitative data from program implementers and recipients in eight clusters where community-wide MDA was delivered. Data collection included semi-structured in-depth interviews (n = 72) and focus group discussions (n = 32). A conceptual framework for drug distribution was constructed to help build an analysis codebook. Case memos were developed for each top-level theme. Community-wide MDA for STH was perceived as a complex intervention with key administrative and social mobilization domains. Key actionable themes included: (1) developing an efficient strategy to allocate reasonable workload for implementers to cover all targeted households; (2) maximizing community drug distributors' motivation through promoting belief in the effectiveness of the intervention and providing sufficient financial incentives; (3) developing effective capacity building strategies for implementers; and (4) implementing a context-adapted community engagement strategy that leverages existing community structures and takes into consideration past community experiences of MDAs. Transitioning from STH control to elimination goals requires significant planning and action to ensure community-wide MDA is delivered with sufficient reach and uptake. We present findings that can inform national deworming programs to increase intervention delivery capacity.


Assuntos
Anti-Helmínticos/uso terapêutico , Controle de Doenças Transmissíveis/organização & administração , Transmissão de Doença Infecciosa/prevenção & controle , Helmintíase/tratamento farmacológico , Helmintíase/prevenção & controle , Administração Massiva de Medicamentos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Erradicação de Doenças/organização & administração , Feminino , Humanos , Entrevistas como Assunto , Quênia , Masculino , Pessoa de Meia-Idade , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/prevenção & controle , Resultado do Tratamento , Adulto Jovem
13.
PLoS Negl Trop Dis ; 14(3): e0008106, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32176703

RESUMO

Lymphatic filariasis has remained endemic in Fiji despite repeated mass drug administration using the well-established and safe combination of diethylcarbamazine and albendazole (DA) since 2002. In certain settings the addition of ivermectin to this combination (IDA) remains a safe strategy and is more efficacious. However, the safety has yet to be described in scabies and soil-transmitted helminth endemic settings like Fiji. Villages of Rotuma and Gau islands were randomised to either DA or IDA. Residents received weight-based treatment unblinded with standard exclusions. Participants were actively found and asked by a nurse about their health daily for the first two days and then asked to seek review for the next five days if unwell. Anyone with severe symptoms were reviewed by a doctor and any serious adverse event was reported to the Medical Monitor and Data Safety Monitoring Board. Of 3612 enrolled and eligible participants, 1216 were randomised to DA and 2396 to IDA. Age and sex in both groups were representative of the population. Over 99% (3598) of participants completed 7 days follow-up. Adverse events were reported by 600 participants (16.7%), distributed equally between treatment groups, with most graded as mild (93.2%). There were three serious adverse events, all judged not attributable to treatment by an independent medical monitor. Fatigue was the most common symptom reported by 8.5%, with headache, dizziness, nausea and arthralgia being the next four most common symptoms. Adverse events were more likely in participants with microfilaremia (43.2% versus 15.7%), but adverse event frequency was not related to the presence of scabies or soil-transmitted helminth infection. IDA has comparable safety to DA with the same frequency of adverse events experienced following community mass drug administration. The presence of co-endemic infections did not increase adverse events. IDA can be used in community programs where preventative chemotherapy is needed for control of lymphatic filariasis and other neglected tropical diseases.


Assuntos
Albendazol/efeitos adversos , Antiparasitários/efeitos adversos , Dietilcarbamazina/efeitos adversos , Inseticidas/efeitos adversos , Ivermectina/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Albendazol/administração & dosagem , Antiparasitários/administração & dosagem , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/tratamento farmacológico , Dietilcarbamazina/administração & dosagem , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Filariose Linfática/tratamento farmacológico , Feminino , Fiji , Helmintíase/tratamento farmacológico , Humanos , Lactente , Inseticidas/administração & dosagem , Ivermectina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Doenças Negligenciadas/tratamento farmacológico , População Rural , Escabiose/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem
14.
Parasit Vectors ; 13(1): 138, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32178706

RESUMO

BACKGROUND: Schistosomiasis and infection by soil-transmitted helminths are some of the world's most prevalent neglected tropical diseases. Infection by more than one parasite (co-infection) is common and can contribute to clinical morbidity in children. Geostatistical analyses of parasite infection data are key for developing mass drug administration strategies, yet most methods ignore co-infections when estimating risk. Infection status for multiple parasites can act as a useful proxy for data-poor individual-level or environmental risk factors while avoiding regression dilution bias. Conditional random fields (CRF) is a multivariate graphical network method that opens new doors in parasite risk mapping by (i) predicting co-infections with high accuracy; (ii) isolating associations among parasites; and (iii) quantifying how these associations change across landscapes. METHODS: We built a spatial CRF to estimate infection risks for Ascaris lumbricoides, Trichuris trichiura, hookworms (Ancylostoma duodenale and Necator americanus) and Schistosoma mansoni using data from a national survey of Rwandan schoolchildren. We used an ensemble learning approach to generate spatial predictions by simulating from the CRF's posterior distribution with a multivariate boosted regression tree that captured non-linear relationships between predictors and covariance in infection risks. This CRF ensemble was compared against single parasite gradient boosted machines to assess each model's performance and prediction uncertainty. RESULTS: Parasite co-infections were common, with 19.57% of children infected with at least two parasites. The CRF ensemble achieved higher predictive power than single-parasite models by improving estimates of co-infection prevalence at the individual level and classifying schools into World Health Organization treatment categories with greater accuracy. The CRF uncovered important environmental and demographic predictors of parasite infection probabilities. Yet even after capturing demographic and environmental risk factors, the presences or absences of other parasites were strong predictors of individual-level infection risk. Spatial predictions delineated high-risk regions in need of anthelminthic treatment interventions, including areas with higher than expected co-infection prevalence. CONCLUSIONS: Monitoring studies routinely screen for multiple parasites, yet statistical models generally ignore this multivariate data when assessing risk factors and designing treatment guidelines. Multivariate approaches can be instrumental in the global effort to reduce and eventually eliminate neglected helminth infections in developing countries.


Assuntos
Coinfecção/parasitologia , Doenças Negligenciadas/parasitologia , Doenças Parasitárias/parasitologia , Adolescente , Ancylostomatoidea/fisiologia , Animais , Anti-Helmínticos/uso terapêutico , Ascaris lumbricoides/fisiologia , Criança , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Fezes/parasitologia , Feminino , Humanos , Masculino , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/epidemiologia , Doenças Parasitárias/epidemiologia , Prevalência , Análise de Regressão , Fatores de Risco , Ruanda , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/tratamento farmacológico , Trichuris/fisiologia
16.
BMC Infect Dis ; 20(1): 119, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041552

RESUMO

BACKGROUND: Paracoccidioidomycosis is a neglected tropical disease, endemic in several countries of South America including Colombia. We report a case of a patient with Chronic Multifocal Paracoccidioidomycosis with long-standing symptoms and a delayed diagnosis caused by several barriers to achieve it. We did a review of the papers published in Colombia about this disease, focusing in clinical data and eco-epidemiology with the finding of a lack of new information on this topic since the 2000 in our region. CASE PRESENTATION: We present a 54-year-old man, farmer in his youth, with a chronic ulcerated lesion in the lower lip similar to a lip carcinoma, a deforming lesion in the nose, and respiratory symptoms with emphysematous lung. Lip biopsy with silver methenamine stain revealed small and large budding yeasts that resembles a "mariner's wheel" confirming Chronic Multifocal Paracoccidioidomycosis. He was treated successfully but subsequently lost to follow up. CONCLUSIONS: It is very important to focus attention, reinforce the search and create networks for the study of neglected tropical diseases. The presented case illustrates a usual clinical presentation, but with a delayed diagnosis due to the difficulties that still occur in some regions like ours for the early recognition of a case of chronic multifocal paracoccidioidomycosis.


Assuntos
Doenças Negligenciadas/diagnóstico , Paracoccidioidomicose/diagnóstico , Biópsia , Colômbia/epidemiologia , Diagnóstico Tardio , Humanos , Lábio/microbiologia , Lábio/patologia , Masculino , Pessoa de Meia-Idade , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/microbiologia , Doenças Negligenciadas/parasitologia , Paracoccidioidomicose/tratamento farmacológico , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/patologia
17.
Exp Parasitol ; 210: 107847, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32004535

RESUMO

Leishmaniasis is an infectious disease that has high endemicity and is among the six parasitic diseases of higher occurrence in the world. The current treatments are limited due to their toxicity, treatment resistance and high cost which have increased the search for new substances of natural origin for its therapy. Based on this, an in vitro biological and chemical investigation was carried out to evaluate the potential of Piper marginatum against Leishmania amazonesis. P. marginatum leaves were collected to obtain the essential oil (EO) and the ethanolic extract (CE). The chemical profile of the CE and fractions was obtained by 1H NMR. The analysis of the EO chemical composition was performed by GC-MS. EO, CE and fractions were submitted to antileishmanial and cytotoxicity assays against macrophages. The chromatographic profiles of EO, CE and fractions showed the presence of phenolic compounds and terpenoids, having 3,4-Methylenedioxypropiophenone as a major compound. All P. marginatum samples showed low toxicity to macrophages. The CE and the methanolic, hexane and ethyl acetate fractions had low cytotoxicity when compared to Pentamidine. All tested samples inhibited growth of L. amazonensis promastigotes. The antileishmanial activity of EO, CE and fractions were evaluated in macrophages infected with L. (L.) amazonensis and treated with the concentrations 1, 10 and 100 µg/mL for 48 h. All samples were active, but EO and CE showed superior activity against amastigote forms when compared to the promastigote forms of L. amazonensis. This work describes for the first time the antileishmanial activity of the species P. marginatum and its cytotoxicity against macrophages, suggesting that it can be an alternative source of natural products in the phytotherapeutic treatment of leishmaniasis.


Assuntos
Leishmania mexicana/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Óleos Voláteis/farmacologia , Piper/química , Extratos Vegetais/farmacologia , Animais , Brasil/epidemiologia , Doenças Endêmicas , Cromatografia Gasosa-Espectrometria de Massas , Concentração Inibidora 50 , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/parasitologia , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/parasitologia , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Óleos Vegetais/química , Óleos Vegetais/isolamento & purificação , Óleos Vegetais/farmacologia
18.
Braz J Infect Dis ; 24(2): 170-177, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32105621

RESUMO

Epidermal parasitic skin diseases encompass scabies, pediculosis, cutaneous larva migrans, myiasis, and tungiasis. Tungiasis is probably the most neglected of all Neglected Tropical Diseases (NTD). It occurs in South America, the Caribbean and Sub-Saharan Africa and affects marginalized populations where people live in extreme poverty. In endemic communities the prevalence can be up to 30% in general population and 85% in children. Over time, chronic pathology develops characterized by hyperkeratosis, edema around the nail rim, fissures, ulcers, deformation and loss of nails. This leads to a pattern of disabilities, eventually resulting in impairment of mobility. Dimeticones are a family of silicon oils with a potential to kill parasites located on top or inside the epidermis by a physical mode of action. They are considered the treatment of choice for pediculosis capitis and pediculosis pubis. With regard to tungiasis, the so called rear abdominal cone of the parasites has been identified as a target for treatment with dimeticones. NYDA®, a mixture of two dimeticones with different viscosity, is the only dimeticone product for which data on the mode of action, efficacy and safety with regard to tungiasis exists. The product has been shown highly effective against embedded sand fleas, even in very intense infection with more than 500 parasites situated on top of each other. A randomized controlled trial showed that seven days after a targeted application of NYDA® 97% (95% CI 94-99%) of the embedded sand fleas had lost all signs of viability. Comprehensive toxicological investigations on the dimeticones contained in NYDA® showed that there is practically no risk of embryotoxicity, fetotoxicity, teratogenicity, and other toxicity. The safety of dimeticones was also demonstrated in clinical trials with a total of 106 participants with tungiasis, in which not a single adverse event was observed.


Assuntos
Dimetilpolisiloxanos/uso terapêutico , Doenças Negligenciadas/tratamento farmacológico , Tungíase/tratamento farmacológico , Animais , Criança , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Doenças Negligenciadas/parasitologia , Dermatopatias Parasitárias/tratamento farmacológico , Dermatopatias Parasitárias/parasitologia
19.
BMC Infect Dis ; 20(1): 62, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959113

RESUMO

BACKGROUND: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. METHODS: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. CONCLUSION: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase Multibacilar/tratamento farmacológico , Hanseníase Paucibacilar/tratamento farmacológico , Minociclina/uso terapêutico , Ofloxacino/uso terapêutico , Rifampina/uso terapêutico , Organização Mundial da Saúde , Adolescente , Adulto , Idoso , Criança , Protocolos Clínicos , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Hansenostáticos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Minociclina/efeitos adversos , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/isolamento & purificação , Doenças Negligenciadas/tratamento farmacológico , Ofloxacino/efeitos adversos , Recidiva , Rifampina/efeitos adversos , Falha de Tratamento , Adulto Jovem
20.
PLoS Negl Trop Dis ; 14(1): e0007860, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31999695

RESUMO

In the past two decades there has been a significant expansion in the number of new therapeutic monoclonal antibodies (mAbs) that are approved by regulators. The discovery of these new medicines has been driven primarily by new approaches in inflammatory diseases and oncology, especially in immuno-oncology. Other recent successes have included new antibodies for use in viral diseases, including HIV. The perception of very high costs associated with mAbs has led to the assumption that they play no role in prophylaxis for diseases of poverty. However, improvements in antibody-expression yields and manufacturing processes indicate this is a cost-effective option for providing protection from many types of infection that should be revisited. Recent technology developments also indicate that several months of protection could be achieved with a single dose. Moreover, new methods in B cell sorting now enable the systematic identification of high-quality antibodies from humanized mice, or patients. This Review discusses the potential for passive immunization against schistosomiasis, fungal infections, dengue, and other neglected diseases.


Assuntos
Anticorpos Monoclonais/farmacologia , Doenças Negligenciadas/tratamento farmacológico , Animais , Dengue/tratamento farmacológico , Desenvolvimento de Medicamentos , Humanos , Imunização Passiva , Camundongos , Micoses/tratamento farmacológico , Esquistossomose/tratamento farmacológico , Medicina Tropical
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