RESUMO
Human schistosomiasis is a parasitic disease caused by an infection with trematodes of the genus Schistosoma. The disease mainly affects impoverished populations. Around 800 million people are exposed to the infection, which is a public health problem in the tropical and subtropical regions of Africa, Asia, the Caribbean and South America. In Brazil, Schistosoma mansoni is the only species that causes schistosomiasis and the disease is widely distributed. Conventional diagnosis of the disease is carried out by detecting eggs using parasitological methods, such as the Kato-Katz test. Schistosomiasis has been reported in all regions of Brazil and is characterized as endemic in seven states in the Northeast Region and two states in the Southeast Region. In 2015, 78,7% of all cases reported in Brazil occurred in the Northeast Region. It is estimated that 1,5 million people is infected with this disease in Brazil and more than 25 millions live in areas with a high risk of transmission. Despite the reduction in mortality and morbidity, schistosomiasis was responsible for 8,756 deaths between 2000 and 2011 and 2,517 deaths between 2015 and 2019 in Brazil and it remains an important public health problem. In the state of Rio de Janeiro, some areas have low endemicity or isolated foci of Schistosoma mansoni and the majority of infected individuals have mild infections. The last survey of the disease in the state of Rio de Janeiro was carried out between 2010 and 2015 in students aged 7 to 17.Schistosomiasis was reported in 10 of the 21 municipalities studied. Of the 5,111 school children screened for S. mansoni infection, 46 (1,65%) were tested positive. Studies carried out in areas of low endemicity in Rio de Janeiro showed that among the 205 patients infected by S. mansoni in Sumidouro, around 84% were aged 14 or over and all, except one individual, had the intestinal form (91,2%) or hepato-intestinal (8,3%) of schistosomiasis. Another study carried out in Sumidouro showed that with tests based on patent Schistosoma egg infection determined by the Kato-Katz test, active infections were diagnosed in eight (8/108) individuals. The intensity of infection expressed by parasite loads ranged from 6 to 72 eggs per gram of feces/individual. The results showed DNA amplification in 32 of the 100 individuals tested by real-time PCR. All individuals with patent ovo infection showed positive DNA amplification. These studies showed that if we only analyzed school-age children using the Kato-Katz test, the majority of the infected population would never be diagnosed with S. mansoni infection. In situations of low endemicity, with low intensities of infection, with low severity in the population and in the most affected age groups, schistosomiasis requires a more sensitive diagnostic approach (e.g. screening by PCR rather than Kato test), otherwise many infected individuals will remain invisible to the healthcare system.
A esquistossomose humana é uma doença parasitária causada por uma infecçâo por vermes sanguíneos do gènero Schistosoma. A doença afeta principalmente populaçoes empobrecidas. Cerca de 800 milhoes de pessoas estâo expostas à infecçâo, sendo um problema de saúde pública nas regioes tropicais e subtropicais de África, Ásia, Caribe e América do Sul. No Brasil, o Schistosoma mansoni é a única espécie causadora da esquistossomose e a doença é amplamente distribuida. O diagnóstico convencional da doença é realizado pela detecçâo dos ovos através de métodos parasitológicos, como o teste de Kato-Katz. A esquistossomose foi notificada em todas as regioes do Brasil, e é caracterizada como endèmica em sete estados da Regiâo Nordeste e dois estados da Regiâo Sudeste. Em 2015, 78,7% de todos os casos notificados no Brasil ocorreram na Regiâo Nordeste. Estima-se que 1,5 milhâo de pessoas estejam infectadas com esta doença no Brasil e mais de 25 milhoes vivam em áreas com alto risco de transmissâo. Apesar da reduçâo da mortalidade e morbidade, a esquistossomose foi relatada em 8.756 mortes entre 2000 e 2011 e em 2.517 mortes entre 2015 e 2019 no Brasil e continua sendo um importante problema de saúde pública. No Estado do Rio de Janeiro, algumas áreas apresentam baixa endemicidade ou focos isolados de Schistosoma mansoni e a maioria dos individuos infectados apresenta infecçoes leves. O último levantamento da doença no Estado do Rio de Janeiro foi realizado entre 2010 e 2015 em estudantes de 7 a 17 anos. A esquistossomose foi relatada em 10 dos 21 municipios estudados. Das 5.111 crianças escolares triadas para infecçâo por S. mansoni, 46 (1,65%) testaram positivo. Estudos realizados em áreas de baixa endemicidade no Rio de Janeiro mostraram que dentre os 205 pacientes infectados por S. mansoni em Sumidouro, cerca de 84% tinham 14 anos ou mais e todos, exceto um individuo, tinham a forma intestinal (91,2%) ou hepato-intestinal (8,3%) da esquistossomose. Outro estudo realizado em Sumidouro, mostrou que testes baseados em infecçâo patente de ovo de Schistosoma determinada pelo teste de Kato-Katz, infecçoes ativas foram diagnosticadas em oito (8/108) individuos. A intensidade de infecçâo expressa pelas cargas parasitárias variou de 6 a 72 ovos por grama de fezes/individuo. Os resultados mostraram amplificaçâo do DNA em 32 dos 100 individuos testados por PCR em tempo real. Todos os indivíduos com infecçâo ovo-patente apresentaram amplificaçâo de DNA positiva. Tais estudos mostraram que se analisarmos apenas crianças em idade escolar pelo teste de Kato-Katz, a maioria da populaçâo infectada nunca seria diagnosticada com infecçâo pelo S. mansoni. Em situaçoes de baixa endemicidade, com baixas intensidades de infecçâo, com baixa gravidade na populaçâo e nas faixas etárias mais afetadas, a esquistossomose requer uma abordagem diagnóstica mais sensivel (por exemplo, triagem por PCR em vez do teste de Kato), caso contràrio, muitos individuos infectados permanecerâo invisiveis para o sistema de saúde.
Assuntos
Doenças Endêmicas , Doenças Negligenciadas , Schistosoma mansoni , Esquistossomose mansoni , Humanos , Brasil/epidemiologia , Animais , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/transmissão , Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/parasitologia , Doenças Endêmicas/estatística & dados numéricos , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/parasitologia , Doenças Negligenciadas/diagnóstico , Esquistossomose/epidemiologia , Esquistossomose/parasitologia , Esquistossomose/diagnóstico , Esquistossomose/transmissãoRESUMO
INTRODUCTION: Chagas disease is spreading faster than expected in different countries, and little progress has been reported in the discovery of new drugs to combat Trypanosoma cruzi infection in humans. Recent clinical trials have ended with small hope. The pathophysiology of this neglected disease and the genetic diversity of parasites are exceptionally complex. The only two drugs available to treat patients are far from being safe, and their efficacy in the chronic phase is still unsatisfactory. AREAS COVERED: This review offers a comprehensive examination and critical review of data reported in the last 10 years, and it is focused on findings of clinical trials and data acquired in vivo in preclinical studies. EXPERT OPINION: The in vivo investigations classically in mice and dog models are also challenging and time-consuming to attest cure for infection. Poorly standardized protocols, availability of diagnosis methods and disease progression markers, the use of different T. cruzi strains with variable benznidazole sensitivities, and animals in different acute and chronic phases of infection contribute to it. More synchronized efforts between research groups in this field are required to put in evidence new promising substances, drug combinations, repurposing strategies, and new pharmaceutical formulations to impact the therapy.
Assuntos
Doença de Chagas , Desenvolvimento de Medicamentos , Tripanossomicidas , Trypanosoma cruzi , Animais , Cães , Humanos , Camundongos , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/parasitologia , Nitroimidazóis/farmacologia , Nitroimidazóis/administração & dosagem , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Recent developments in the use of natural product-based molecules as antiparasitic agents for Malaria, leishmaniasis (LE), Chagas disease (CD), and Human African trypanosomiasis (HAT) are reviewed. The role of diverse plants in developing bioactive species is discussed in addition to analyzing the structural diversity of natural products as active agents and the diverse biological applications in CD, HAT, LE, and Malaria. This review focuses on medicinal chemistry, emphasizing the structural characteristics of natural molecules as bioactive agents against parasitic infections caused by Leishmania, Trypanosoma, and Plasmodium parasites.
Assuntos
Antiprotozoários , Produtos Biológicos , Doença de Chagas , Leishmaniose , Malária , Tripanossomíase Africana , Animais , Humanos , Antiparasitários/farmacologia , Antiparasitários/uso terapêutico , Antiparasitários/química , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Antiprotozoários/química , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/química , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/parasitologia , Tripanossomíase Africana/tratamento farmacológico , Leishmaniose/tratamento farmacológico , Doença de Chagas/tratamento farmacológico , Malária/tratamento farmacológicoRESUMO
BACKGROUND: Neglected tropical diseases affect the most vulnerable populations and cause chronic and debilitating disorders. Socioeconomic vulnerability is a well-known and important determinant of neglected tropical diseases. For example, poverty and sanitation could influence parasite transmission. Nevertheless, the quantitative impact of socioeconomic conditions on disease transmission risk remains poorly explored. METHODS: This study investigated the role of socioeconomic variables in the predictive capacity of risk models of neglected tropical zoonoses using a decade of epidemiological data (2007-2018) from Brazil. Vector-borne diseases investigated in this study included dengue, malaria, Chagas disease, leishmaniasis, and Brazilian spotted fever, while directly-transmitted zoonotic diseases included schistosomiasis, leptospirosis, and hantaviruses. Environmental and socioeconomic predictors were combined with infectious disease data to build environmental and socioenvironmental sets of ecological niche models and their performances were compared. RESULTS: Socioeconomic variables were found to be as important as environmental variables in influencing the estimated likelihood of disease transmission across large spatial scales. The combination of socioeconomic and environmental variables improved overall model accuracy (or predictive power) by 10% on average (P < 0.01), reaching a maximum of 18% in the case of dengue fever. Gross domestic product was the most important socioeconomic variable (37% relative variable importance, all individual models exhibited P < 0.00), showing a decreasing relationship with disease indicating poverty as a major factor for disease transmission. Loss of natural vegetation cover between 2008 and 2018 was the most important environmental variable (42% relative variable importance, P < 0.05) among environmental models, exhibiting a decreasing relationship with disease probability, showing that these diseases are especially prevalent in areas where natural ecosystem destruction is on its initial stages and lower when ecosystem destruction is on more advanced stages. CONCLUSIONS: Destruction of natural ecosystems coupled with low income explain macro-scale neglected tropical and zoonotic disease probability in Brazil. Addition of socioeconomic variables improves transmission risk forecasts on tandem with environmental variables. Our results highlight that to efficiently address neglected tropical diseases, public health strategies must target both reduction of poverty and cessation of destruction of natural forests and savannas.
Assuntos
Doença de Chagas , Doenças Transmissíveis , Animais , Humanos , Ecossistema , Pobreza , Zoonoses/epidemiologia , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/parasitologiaRESUMO
Neglected tropical diseases are a diverse group of communicable diseases that are endemic in low- or low-to-middle-income countries located in tropical and subtropical zones. The number and availability of drugs for treating these diseases are low, the administration route is inconvenient in some cases, and most of them have safety, efficacy, or adverse/toxic reaction issues. The need for developing new drugs to deal with these issues is clear, but one of the most drastic consequences of this negligence is the lack of interest in the research and development of new therapeutic options among major pharmaceutical companies. Positive changes have been achieved over the last few years, although the overall situation remains alarming. After more than one decade since the original work reviewing antiprotozoal agents came to light, now it is time to question ourselves: How has the scenario for the treatment of protozoal diseases such as malaria, leishmaniasis, human African trypanosomiasis, and American trypanosomiasis changed? This review covers the last decade in terms of the drugs currently available for the treatment of these diseases as well as the clinical candidates being currently investigated.
Assuntos
Antiprotozoários/farmacologia , Doenças Negligenciadas/tratamento farmacológico , Infecções por Protozoários/tratamento farmacológico , Animais , Desenvolvimento de Medicamentos/tendências , Humanos , Doenças Negligenciadas/parasitologia , Infecções por Protozoários/parasitologiaRESUMO
The severity of chronic schistosomiasis has been mainly associated with the intensity and extension of the inflammatory response induced by egg-secreted antigens in the host tissue, especially in the liver and intestine. During acute schistosomiasis, eosinophils account for approximately 50% of the cells that compose the liver granulomas; however, the role of this cell-type in the pathology of schistosomiasis remains controversial. In the current study, we compared the parasite burden and liver immunopathological changes during experimental schistosomiasis in wild-type (WT) BALB/c mice and BALB/c mice selectively deficient for the differentiation of eosinophils (ΔdblGATA). Our data demonstrated that the absence of eosinophil differentiation did not alter the S. mansoni load or the liver retention of parasite eggs; however, there were significant changes in the liver immune response profile and tissue damage. S. mansoni infection in ΔdblGATA mice resulted in significantly lower liver concentrations of IL-5, IL-13, IL-33, IL-17, IL-10, and TGF-ß and higher concentrations of IFN-γ and TNF-α, as compared to WT mice. The changes in liver immune response observed in infected ΔdblGATA mice were accompanied by lower collagen deposition, but higher liver damage and larger granulomas. Moreover, the absence of eosinophils resulted in a higher mortality rate in mice infected with a high parasite load. Therefore, the data indicated that eosinophils participate in the establishment and/or amplification of liver Th-2 and regulatory response induced by S. mansoni, which is necessary for the balance between liver damage and fibrosis, which in turn is essential for modulating disease severity.
Assuntos
Eosinófilos/imunologia , Imunidade/imunologia , Hepatopatias/imunologia , Fígado/imunologia , Doenças Negligenciadas/imunologia , Esquistossomose mansoni/imunologia , Animais , Citocinas/imunologia , Modelos Animais de Doenças , Eosinófilos/parasitologia , Feminino , Fibrose/imunologia , Fibrose/parasitologia , Granuloma/imunologia , Granuloma/parasitologia , Intestinos/imunologia , Intestinos/parasitologia , Fígado/parasitologia , Hepatopatias/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Doenças Negligenciadas/parasitologiaRESUMO
BACKGROUND: Envenomation by the South American Lonomia saturniid caterpillars, named lonomism, constitutes an emerging and somewhat neglected public health issue in Argentina and neighboring countries. Considering that there is an intricate relationship between environment and human health in such cases, this study aimed to analyze the eco-epidemiological profile of 40 accidents and 33 occurrences of Lonomia spp. in Misiones (Argentina) between January 2014 and May 2020. METHODOLOGY/PRINCIPAL FINDINGS: We described the eco-epidemiological variables and characterized the abiotic scenario of such cases. Additionally, we obtained a density map that shows the punctual intensity of Lonomia records throughout Misiones. Most of the accidents occurred in the Department of Guaraní and involved male victims younger than 20 years old. The accidental/occasional occurrence of Lonomia spp. (considering both adult and caterpillar stages together) was significantly higher in the rural area, whereas only adult specimens were found in urban areas. We determined that the presence of this insect in Misiones is positively related to higher temperatures and solar radiation, and larger precipitation and evapotranspiration throughout the year. CONCLUSION/SIGNIFICANCE: This study represents an initial step towards the global understanding of lonomism as a public health problem in Argentina. It provides a map of the risk level for this envenomation in Misiones, which could help authorities address public health policy efforts to implement sustainable strategies for prevention and response to this threat in Northeastern Argentina and neighboring regions.
Assuntos
Venenos de Artrópodes/toxicidade , Mordeduras e Picadas de Insetos/parasitologia , Larva/fisiologia , Mariposas/fisiologia , Adolescente , Adulto , Idoso , Animais , Argentina/epidemiologia , Criança , Pré-Escolar , Ecossistema , Feminino , Humanos , Lactente , Mordeduras e Picadas de Insetos/epidemiologia , Larva/classificação , Masculino , Pessoa de Meia-Idade , Mariposas/classificação , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/parasitologia , Saúde Pública , Adulto JovemRESUMO
Control of human ascariasis, the most prevalent neglected tropical disease globally affecting 450 million people, mostly relies on mass drug administration of anthelmintics. However, chemotherapy alone is not efficient due to the high re-infection rate for people who live in the endemic area. The development of a vaccine that reduces the intensity of infection and maintains lower morbidity should be the primary target for infection control. Previously, our group demonstrated that immunization with crude Ascaris antigens in mice induced an IgG-mediated protective response with significant worm reduction. Here, we aimed to develop a multipeptide chimera vaccine based on conserved B-cell epitopes predicted from 17 common helminth proteomes using a bioinformatics algorithm. More than 480 B-cell epitopes were identified that are conserved in all 17 helminths. The Ascaris-specific epitopes were selected based on their reactivity to the pooled sera of mice immunized with Ascaris crude antigens or infected three times with A. suum infective eggs. The top 35 peptides with the strongest reactivity to Ascaris immune serum were selected to construct a chimeric antigen connected in sequence based on conformation. This chimera, called ASCVac-1, was produced as a soluble recombinant protein in an Escherichia coli expression system and, formulated with MPLA, was used to immunize mice. Mice immunized with ASCVac-1/MPLA showed around 50% reduced larvae production in the lungs after being challenged with A. suum infective eggs, along with significantly reduced inflammation and lung tissue/function damage. The reduced parasite count and pathology in infected lungs were associated with strong Th2 immune responses characterized by the high titers of antigen-specific IgG and its subclasses (IgG1, IgG2a, and IgG3) in the sera and significantly increased IL-4, IL-5, IL-13 levels in lung tissues. The reduced IL-33 titers and stimulated eosinophils were also observed in lung tissues and may also contribute to the ASCVac-1-induced protection. Taken together, the preclinical trial with ASCVac-1 chimera in a mouse model demonstrated its significant vaccine efficacy associated with strong IgG-based Th2 responses, without IgE induction, thus reducing the risk of an allergic response. All results suggest that the multiepitope-based ASCVac-1 chimera is a promising vaccine candidate against Ascaris sp. infections.
Assuntos
Antígenos de Helmintos/administração & dosagem , Ascaríase/prevenção & controle , Ascaris suum/imunologia , Doenças Negligenciadas/prevenção & controle , Vacinas Protozoárias/administração & dosagem , Animais , Antígenos de Helmintos/imunologia , Ascaríase/imunologia , Ascaríase/parasitologia , Ascaríase/patologia , Ascaris suum/isolamento & purificação , Feminino , Humanos , Pulmão/imunologia , Pulmão/parasitologia , Pulmão/patologia , Camundongos , Doenças Negligenciadas/imunologia , Doenças Negligenciadas/parasitologia , Doenças Negligenciadas/patologia , Vacinas Protozoárias/imunologia , Células Th2/imunologia , Eficácia de Vacinas , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologiaRESUMO
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. During the chronic phase of disease, while most infected people do not present symptoms, characterizing the asymptomatic form, some patients develop the cardiac form or chronic chagasic cardiomyopathy, which is considered the most severe manifestation of this disease. Considering that the activation of the PI3Kγ signaling pathway is essential for an efficient immune response against T. cruzi infection, we evaluated the PIK3CG C > T (rs1129293) polymorphism in exon 3 of this gene, which encodes the catalytic subunit of PI3Kγ. The PIK3CG CT and TT genotypes were found to be associated with an increased risk of developing the cardiac form of the disease rather than the asymptomatic or digestive forms. In conclusion, the presence of the T allele at single or double doses may differentiate the cardiac from other clinical manifestations of Chagas disease. This finding should help in further studies to evaluate the mechanisms underlying the differential association of PIK3CG in Chagas disease.
Assuntos
Domínio Catalítico/genética , Cardiomiopatia Chagásica/genética , Doença de Chagas/genética , Doença de Chagas/parasitologia , Classe Ib de Fosfatidilinositol 3-Quinase/genética , Polimorfismo de Nucleotídeo Único , Trypanosoma cruzi , Cardiomiopatia Chagásica/parasitologia , Classe Ib de Fosfatidilinositol 3-Quinase/metabolismo , Variação Genética , Genótipo , Coração/parasitologia , Interações Hospedeiro-Parasita , Humanos , Doenças Negligenciadas/genética , Doenças Negligenciadas/parasitologia , Transdução de SinaisRESUMO
Cutaneous Leishmaniasis (CL) is a vector-borne disease caused by Leishmania species and transmitted by infected female sand flies. CL is widely distributed in Brazil, but knowledge about vectors and transmission cycles could be complex according to localities. The sand fly fauna in Rondônia State is extensive, diverse, and largely unexplored. Although the state records a mean of 1,000 CL cases per year, the vectors of CL are unknown. The aim of this study was to assess phlebotomine sand fly fauna composition using diversity indexes (Shannon [H'] and Simpson [1/D]) and to detect the prevalence of Leishmania infection to verify potential vectors in three ecotopes: (i) forest fragment (FF), (ii) forest edge (FE), and (iii) peridomicile (PE). Captures were performed in four rural districts in the municipality of Porto Velho. A total of 7,026 specimens were captured comprising 72 species, and individuals classified in subgenus level. Overall, the most abundant species were Lutzomyia davisi (n: 1,105), Lutzomyia melloi (n: 760), Lutzomyia auraensis (n: 738) and Lutzomyia antunesi (n: 479). Fauna was most diverse in the FF ecotope (H' = 20.2, 1/D = 11.2), followed by the FE (H' = 18.0, 1/D = 10.1) and PE (H' = 16.6, 1/D = 10.1) ecotopes. Leishmania DNA was detected in 24 of 232 pools. In every ecotope, Leishmania naiffi DNA was identified in the following sand fly species: Lu. antunesi, Lu. davisi, Lu. hirsuta hirsuta, Lu. shawi, Lu. sordellii and Lu. (Trichophoromyia) spp. This observation may indicate that a Le. naiffi transmission focus is present in the study localities. In addition, Leishmania lainsoni was detected in Lutzomyia (Trichophoromyia) spp. Our findings show that sand fly fauna in the study localities is diverse, that Leishmania parasites are circulating in all three ecotopes, and that some sand fly species may be implicated in the transmission of Leishmania to humans in localities evaluated.
Assuntos
Insetos Vetores/parasitologia , Leishmania/isolamento & purificação , Leishmaniose Cutânea/transmissão , Doenças Negligenciadas/parasitologia , Psychodidae/parasitologia , Animais , Brasil/epidemiologia , Feminino , Florestas , Humanos , Leishmania/genética , Leishmaniose Cutânea/epidemiologia , Doenças Negligenciadas/epidemiologiaRESUMO
The World Health Organisation (WHO) has placed twenty diseases into a group known as neglected tropical diseases (NTDs), twelve of them being parasitic diseases: Chagas' disease, cysticercosis/taeniasis, echinococcosis, food-borne trematodiasis, human African trypanosomiasis (sleeping sickness), leishmaniasis, lymphatic filariasis, onchocerciasis (river blindness), schistosomiasis, soil-transmitted helminthiasis (ascariasis, hookworm, trichuriasis), guinea-worm and scabies. Such diseases affect millions of people in developing countries where one of the main problems concerning the control of these diseases is diagnosis-based due to the most affected areas usually being far from laboratories having suitable infrastructure and/or being equipped with sophisticated equipment. Advances have been made during the last two decades regarding standardising and introducing techniques enabling diagnoses to be made in remote places, i.e., the loop-mediated isothermal amplification (LAMP) technique. This technique's advantages include being able to perform it using simple equipment, diagnosis made directly in the field, low cost of each test and the technique's high specificity. Using this technique could thus contribute toward neglected parasite infection (NPI) control and eradication programmes. This review describes the advances made to date regarding LAMP tests, as it has been found that even though several studies have been conducted concerning most NPI, information is scarce for others.
Assuntos
Técnicas de Diagnóstico Molecular/métodos , Doenças Negligenciadas/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/métodos , Parasitos/isolamento & purificação , Doenças Parasitárias/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Animais , Humanos , Doenças Negligenciadas/parasitologia , Doenças Parasitárias/parasitologiaRESUMO
OBJECTIVE: to describe schistosomiasis control actions and its epidemiological situation in Pernambuco, Brazil, 2010-2016. METHODS: this was a descriptive study using data from the Schistosomiasis Surveillance and Control Program Information System for 116 municipalities, including indicators related to control actions (population surveyed, tests performed, treatment coverage) and epidemiological actions (positivity, parasite load, other helminthiases). RESULTS: Health Regions II, III, IV, V and XII, which are traditionally endemic, registered higher average percentages for control actions (population surveyed [6.5%, 6.0%, 2.0%, 12.0%, and 13.0%], tests performed [75.0%, 75.5%, 74.0%, 74.0%, and 68.5%], and treatment coverage [71.0%, 82.5%, 82.0%, 91.0%, and 73.0%], respectively), and higher average percentages for epidemiological variables (positivity [3.5%, 8.0%, 1.0%, 2.0%, and 6.5%], high parasite load [0.1%, 0.7%, 0.02%, 0.03%, and 0.5%], and other helminthiases [4.0%, 11.0%, 4.0%, 6.0%, and 8.0%], respectively). CONCLUSION: control actions need to be expanded in traditionally endemic regions.
Assuntos
Helmintíase/epidemiologia , Vigilância em Saúde Pública , Esquistossomose/epidemiologia , Brasil/epidemiologia , Humanos , Sistemas de Informação , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/parasitologiaRESUMO
BACKGROUND: Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials. METHODS/DESIGN: MULTIBENZ is a phase II, randomized, noninferiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018. CONCLUSION: This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03191162. Registered on 19 June 2017.
Assuntos
Doença de Chagas/tratamento farmacológico , Doenças Negligenciadas/parasitologia , Nitroimidazóis/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/isolamento & purificação , Adulto , Assistência ao Convalescente , Argentina/epidemiologia , Brasil/epidemiologia , Estudos de Casos e Controles , Doença de Chagas/parasitologia , Doença Crônica , Colômbia/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Nitroimidazóis/farmacocinética , Carga Parasitária/estatística & dados numéricos , Segurança , Espanha/epidemiologia , Resultado do Tratamento , Tripanossomicidas/farmacocinética , Trypanosoma cruzi/genéticaRESUMO
ABSTRACT 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
Animais , Criança , Feminino , Humanos , Masculino , Dimetilpolisiloxanos/uso terapêutico , Tungíase/tratamento farmacológico , Doenças Negligenciadas/tratamento farmacológico , Dermatopatias Parasitárias/parasitologia , Dermatopatias Parasitárias/tratamento farmacológico , Ensaios Clínicos como Assunto , Doenças Negligenciadas/parasitologiaRESUMO
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 de Plantas/química , Óleos de Plantas/isolamento & purificação , Óleos de Plantas/farmacologiaRESUMO
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/patologiaRESUMO
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/parasitologiaRESUMO
Visceral leishmaniasis (VL) is a highly neglected disease that is present in several countries worldwide. Present-day treatments against this disease are unsuitable, mainly due to the toxicity and/or high cost of drugs. In addition, the development of vaccines is still insufficient. In this scenario, a prompt VL diagnosis was deemed necessary, although sensitivity and/or specificity values of the tests have been. In this context, new antigenic candidates should be identified to be employed in a more precise diagnosis of canine and human VL. In this light, the present study evaluated the diagnostic efficacy of the Leishmania infantum pyridoxal kinase (PK) protein, applied in its recombinant version (rPK). In addition, one specific B-cell epitope derived of the PK sequence was predicted, synthetized, and evaluated as diagnostic marker. Results in ELISA tests showed that the antigens were highly sensitive to VL identification in dogs and human sera, presenting a low reactivity with VL-related disease samples. The recombinant A2 (rA2) protein and L. infantum antigenic preparation (SLA), used as controls, also proved to be highly sensitive in detecting symptomatic cases, although a low sensitivity was found when asymptomatic sera were analyzed. High cross-reactivity was also found when these antigens were evaluated against VL-related disease samples. The post-therapeutic serological follow-up showed that anti-rPK and anti-peptide IgG antibody levels decreased in significant levels after treatment. By contrast, the presence of high levels of the anti-rA2 and anti-SLA antibodies was still detected after therapy. In conclusion, rPK and its specific B-cell epitope should be considered for future studies as a diagnostic marker for canine and human VL.
Assuntos
Anticorpos Antiprotozoários/sangue , Doenças do Cão/diagnóstico , Leishmania infantum/enzimologia , Leishmaniose Visceral/diagnóstico , Doenças Negligenciadas/diagnóstico , Proteínas de Protozoários/imunologia , Piridoxal Quinase/imunologia , Sequência de Aminoácidos , Animais , Antígenos de Protozoários/química , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Reações Cruzadas , Doenças do Cão/parasitologia , Cães , Ensaio de Imunoadsorção Enzimática , Epitopos de Linfócito B/química , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Humanos , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/veterinária , Doenças Negligenciadas/parasitologia , Doenças Negligenciadas/veterinária , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Piridoxal Quinase/química , Piridoxal Quinase/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Sensibilidade e Especificidade , Testes SorológicosRESUMO
Resumo Objetivo: descrever as ações de controle e a situação epidemiológica da esquistossomose, em Pernambuco, Brasil, 2010-2016. Métodos: estudo descritivo, com dados do Sistema de Informação do Programa de Vigilância e Controle da Esquistossomose em 116 municípios, incluindo indicadores relacionados às ações de controle (população trabalhada, exames realizados, cobertura de tratamento) e epidemiológicas (positividade, carga parasitária, outras helmintoses). Resultados: as II, III, IV, V e XII regiões de saúde do estado, tradicionalmente endêmicas, registraram maiores percentuais médios para ações de controle (população trabalhada [6,5%, 6,0%, 2,0%, 12,0% e 13,0%], exames realizados [75,0%, 75,5%, 74,0%, 74,0% e 68,5%] e cobertura de tratamento [71,0%, 82,5%, 82,0%, 91,0% e 73,0%], respectivamente), e maiores percentuais médios para variáveis epidemiológicas (positividade [3,5%, 8,0%, 1,0%, 2,0% e 6,5%], alta carga parasitária [0,1%, 0,7%, 0,02%, 0,03% e 0,5%] e outras helmintoses [4,0%, 11,0%, 4,0%, 6,0% e 8,0%], respectivamente). Conclusão: deve-se ampliar as ações de controle nas regiões tradicionalmente endêmicas.
Resumen Objetivo: describir las acciones de control y la situación epidemiológica de la esquistosomiasis, Pernambuco, Brasil, 2010-2016. Métodos: estudio descriptivo utilizando datos del Sistema de Información del Programa de Vigilancia y Control de Esquistosomiasis en 116 municipios, incluyendo indicadores relacionados con acciones de control (población trabajada, pruebas realizadas, cobertura del tratamiento) y epidemiológicas (positividad, carga parasitaria, otros helmintos). Resultados: las regiones de salud II, III, IV, V y XII del estado, tradicionalmente endémicas, registraron porcentajes promedios más altos para las acciones de control (población trabajada [6,5%, 6,0%, 2,0%, 12,0% y 13,0%], exámenes [75,0%, 75,5%, 74,0%, 74,0% y 68,5%] y tratamiento [71,0%, 82,5%, 82,0%, 91,0% y 73,0%], respectivamente), y porcentajes promedios más altos para variables epidemiológicas (positividad [3,5%, 8,0%, 1,0%, 2,0% y 6,5%], alta carga parasitaria [0,1%, 0,7%, 0,02%, 0,03% y 0,5%] y otros helmintos [4,0%, 11,0%, 4,0%, 6,0% y 8,0%], respectivamente). Conclusión: ampliar las acciones de control en regiones tradicionalmente endémicas.
Abstract Objective: to describe schistosomiasis control actions and its epidemiological situation in Pernambuco, Brazil, 2010-2016. Methods: this was a descriptive study using data from the Schistosomiasis Surveillance and Control Program Information System for 116 municipalities, including indicators related to control actions (population surveyed, tests performed, treatment coverage) and epidemiological actions (positivity, parasite load, other helminthiases). Results: Health Regions II, III, IV, V and XII, which are traditionally endemic, registered higher average percentages for control actions (population surveyed [6.5%, 6.0%, 2.0%, 12.0%, and 13.0%], tests performed [75.0%, 75.5%, 74.0%, 74.0%, and 68.5%], and treatment coverage [71.0%, 82.5%, 82.0%, 91.0%, and 73.0%], respectively), and higher average percentages for epidemiological variables (positivity [3.5%, 8.0%, 1.0%, 2.0%, and 6.5%], high parasite load [0.1%, 0.7%, 0.02%, 0.03%, and 0.5%], and other helminthiases [4.0%, 11.0%, 4.0%, 6.0%, and 8.0%], respectively). Conclusion: control actions need to be expanded in traditionally endemic regions.