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PURPOSE OF REVIEW: This review aims at highlighting the need to better understand the pathogenesis and natural history of endomyocardial fibrosis when set against its changing endemicity and disease burden, improvements in diagnosis, and new options for clinical management. RECENT FINDINGS: Progress in imaging diagnostic techniques and availability of new targets for drug and surgical treatment of heart failure are contributing to earlier diagnosis and may lead to improvement in patient survival. Endomyocardial fibrosis was first described in Uganda by Davies more than 70 years ago (1948). Despite its poor prognosis, the etiology of this neglected tropical restrictive cardiomyopathy still remains enigmatic nowadays. Our review reflects on the journey of scientific discovery and construction of the current guiding concepts on this mysterious and fascinating condition, bringing to light the contemporary knowledge acquired over these years. Here we describe novel tools for diagnosis, give an overview of the improvement in clinical management, and finally, suggest research themes that can help improve patient outcomes focusing (whenever possible) on novel players coming into action.
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Fibrose Endomiocárdica , Insuficiência Cardíaca/terapia , Doenças Negligenciadas , Cardiomiopatia Restritiva/diagnóstico , Cardiomiopatia Restritiva/etiologia , Cardiomiopatia Restritiva/patologia , Cardiomiopatia Restritiva/terapia , Efeitos Psicossociais da Doença , Países em Desenvolvimento , Progressão da Doença , Fibrose Endomiocárdica/diagnóstico , Fibrose Endomiocárdica/epidemiologia , Fibrose Endomiocárdica/etiologia , Fibrose Endomiocárdica/terapia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Humanos , Doenças Negligenciadas/diagnóstico , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/etiologia , Doenças Negligenciadas/terapia , PobrezaRESUMO
Herbs are commonly used worldwide for the treatment of various diseases, constituting a multi-billion dollar market. Unfortunately, hepatotoxicity induced by herbs is also common. The true incidence and prevalence are not known. There is need for more strict regulations andexperimental and pre-clinical studies regarding its efficacy and safety. There is no gold standard for the diagnosis of herbs-induced liver injury (HILI) and it constitutes a diagnostic challenge for the clinician, whereestablishing causality could be cumbersome. Clinical presentation varies from asymptomatic cases with mildly abnormal liver tests to fulminant liver failure requiring liver transplantation. In this review, we will discuss the epidemiology, clinical manifestations, challenges and diagnostic approach of HILI and will also present some exemplary cases from the University of Miami, Division of Hepatology.
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Doença Hepática Induzida por Substâncias e Drogas , Suplementos Nutricionais/efeitos adversos , Doenças Negligenciadas , Preparações de Plantas/efeitos adversos , Plantas Medicinais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Humanos , Doenças Negligenciadas/diagnóstico , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/etiologia , Estados Unidos/epidemiologiaRESUMO
We present a case of primary infertility with features of hypogonadism in a male patient with lepromatous leprosy who had remained undiagnosed for 3 years. On investigation, azoospermia and deranged gonadotropin levels with normal serum testosterone were noted and the patient was initiated on multibacillary-multidrug therapy with the primary aim of treating the disease. Although the cutaneous lesions improved within 6 weeks, remarkably infertility was reversed in 2 months-with concomitant normalization of luteinizing hormone, follicle stimulating hormone, and sperm count-an outcome that was unexpected. While reiterating leprosy as a cause of infertility, we discuss the probable mechanism for the efficacy of multidrug therapy in what seemed to be an irreversible outcome of advanced lepromatous leprosy.
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Infertilidade , Hanseníase Virchowiana , Adulto , Quimioterapia Combinada , Hormônio Foliculoestimulante/uso terapêutico , Humanos , Hipogonadismo/tratamento farmacológico , Hipogonadismo/etiologia , Hipogonadismo/microbiologia , Infertilidade/tratamento farmacológico , Infertilidade/etiologia , Hansenostáticos/uso terapêutico , Hanseníase/complicações , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/patologia , Hormônio Luteinizante/uso terapêutico , Masculino , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/etiologia , Doenças Negligenciadas/microbiologia , Testosterona/sangueRESUMO
The E3 deubiquitinating enzyme ubiquitin-specific proteolytic enzyme 21 (USP21) plays vital roles in physiological activities and is required for Treg-cell-mediated immune tolerance. Using a murine model infected with Schistosoma japonicum, we observed that there were more cercariae developed into adults and more eggs deposited in the livers of the USP21fl/flFOXP3Cre (KO) mice. However, immunohistochemistry showed that the degree of egg granuloma formation and liver fibrosis was reduced. In USP21fl/flFOXP3Cre mice, levels of IFN-gamma, IL-4, anti-soluble egg antigen (SEA) IgG and anti-soluble worm antigen preparation (SWAP) IgG increased in blood, as determined using ELISAs and multiplex fluorescent microsphere immunoassays, while the levels of IL-10, lL-17A, IL-23, IL-9, and anti-SEA IgM decreased. In addition, the levels of the USP21 protein and mRNA in the liver and spleen of KO mice decreased. We further observed increased Th1 responses amplified by Tregs (regulatory T cells) and compromised Th17 responses, which alleviated the liver immunopathology. We speculated that these changes were related to polarization of Th1-like Tregs. Our results revealed the roles of USP21 in Treg-cell-mediated regulation of immune interactions between Schistosoma and its host. USP21 may have potential for regulating hepatic fibrosis in patients with schistosomiasis.
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Suscetibilidade a Doenças , Esquistossomose Japônica/etiologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Ubiquitina Tiolesterase/genética , Animais , Citocinas/sangue , Citocinas/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Predisposição Genética para Doença , Imunofenotipagem , Fígado/imunologia , Fígado/parasitologia , Fígado/patologia , Camundongos , Camundongos Knockout , Doenças Negligenciadas/etiologia , Doenças Negligenciadas/imunologia , Baço/imunologia , Baço/parasitologia , Baço/patologiaRESUMO
January 30, 2020 is the first-ever World Neglected Tropical Diseases Day (World NTD Day), a day when we celebrate the achievements made towards control of the world's NTDs, yet recognize the daunting challenges we face in the control and elimination of these conditions.
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Infecções Bacterianas/prevenção & controle , Saúde Global , Doenças Negligenciadas/epidemiologia , Doenças Parasitárias/prevenção & controle , Viroses/prevenção & controle , Organização Mundial da Saúde/organização & administração , Erradicação de Doenças , Doenças Negligenciadas/etiologia , Clima TropicalRESUMO
BACKGROUND: Neglected tropical diseases (NTDs) affect more than one billion people living in vulnerable conditions. In spite of initiatives recently contributing to fill NTDs gaps on national and local prevalence and distribution, more epidemiological data are still needed for effective control and elimination interventions. MAIN TEXT: Mozambique is considered one of the countries with highest NTDs burden although available data is scarce. This study aims to conduct a systematic review on published available data about the burden and distribution of the different NTDs across Mozambique since January 1950 until December 2018. We identified manuscripts from electronic databases (Pubmed, EmBase and Global Health) and paper publications and grey literature from Mozambique Ministry of Health. Manuscripts fulfilling inclusion criteria were: cross-sectional studies, ecological studies, cohorts, reports, systematic reviews, and narrative reviews capturing epidemiological information of endemic NTDs in Mozambique. Case-control studies, letters to editor, case reports and case series of imported cases were excluded. A total of 466 manuscripts were initially identified and 98 were finally included after the revision following PRISMA guidelines. Eleven NTDs were reported in Mozambique during the study span. Northern provinces (Nampula, Cabo Delgado, Niassa, Tete and Zambezia) and Maputo province had the higher number of NTDs detected. Every disease had their own report profile: while schistosomiasis have been continuously reported since 1952 until nowadays, onchocerciasis and cysticercosis last available data is from 2007 and Echinococcosis have never been evaluated in the country. Thus, both space and time gaps on NTDs epidemiology have been identified. CONCLUSIONS: This review assembles NTDs burden and distribution in Mozambique. Thus, contributes to the understanding of NTDs epidemiology in Mozambique and highlights knowledge gaps. Hence, the study provides key elements to progress towards the control and interruption of transmission of these diseases in the country.
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Doenças Negligenciadas/epidemiologia , Humanos , Moçambique/epidemiologia , Doenças Negligenciadas/classificação , Doenças Negligenciadas/etiologiaRESUMO
Reducing the burden of neglected tropical diseases (NTDs) is one of the key strategic targets advanced by the Sustainable Development Goals. Despite the unprecedented effort deployed for NTD elimination in the past decade, their control, mainly through drug administration, remains particularly challenging: persistent poverty and repeated exposure to pathogens embedded in the environment limit the efficacy of strategies focused exclusively on human treatment or medical care. Here, we present a simple modelling framework to illustrate the relative role of ecological and socio-economic drivers of environmentally transmitted parasites and pathogens. Through the analysis of system dynamics, we show that periodic drug treatments that lead to the elimination of directly transmitted diseases may fail to do so in the case of human pathogens with an environmental reservoir. Control of environmentally transmitted diseases can be more effective when human treatment is complemented with interventions targeting the environmental reservoir of the pathogen. We present mechanisms through which the environment can influence the dynamics of poverty via disease feedbacks. For illustration, we present the case studies of Buruli ulcer and schistosomiasis, two devastating waterborne NTDs for which control is particularly challenging.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'.
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Saúde Global , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/prevenção & controle , Medicina Tropical , Conservação dos Recursos Naturais , Meio Ambiente , Humanos , Doenças Negligenciadas/etiologia , PobrezaRESUMO
BACKGROUND: Large numbers of people are suffering from a group of diseases that mainly affect developing countries, as there are no available or affordable products for prevention or treatment. Research and development (R&D) for these diseases is still a low priority on the health agenda. Brazil, Russia, India, China and South Africa (BRICS) are quickly growing economies and having more and more positive impact on global health. Additionally, their R&D capacity is believed to be enhanced through decades of investment in education and life science research. The BRICS, as a group of emerging and developing countries, are expected to make greater contributions to solving the problem that mainly affects the entire developing countries community. However, there has been little research to provide a macroscopic overview of BRICS' effort in R&D for neglected diseases. The aim of this study is to investigate scientific production in BRICS countries in this area and their main research hotspots. METHODS: Global relevant literature was searched without time limits through PubMed and high yield countries were identified using GoPubMed. Literature up to the end of 2013 from the BRICS was obtained and high frequency words were extracted and clustered using Bibliography Item Co-occurrence Mining System 2.0 (BICOMS) and Graphical Clustering Toolkit 1.0 (gCLUTO). RESULTS: In total, 32, 47, 51, 31 and 44 high frequency words from Brazil, Russia, India, China and South Africa respectively were extracted for clustering analysis. The clustering indicated that eight diseases were research hotspots in BRICS countries. India had the most extensive hotspots and Brazil came in second. The other three countries shared common research foci: helminthiasis, Human Immunodeficiency Virus infection and Acquired Immune Deficiency Syndrome (HIV/AIDS) and tuberculosis. CONCLUSIONS: Developed countries still make the majority of contributions to R&D on neglected diseases, but BRICS countries are playing a growing role. Instead of the "big three diseases" (HIV/AIDS, malaria and tuberculosis) recognized by WHO, the BRICS focus more on major causes of disease burden in their own countries. Disease burden and domestic policy, especially patent law, exert primary influence on the research focus.
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Bibliometria , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/etiologia , China , Humanos , Índia , Projetos de Pesquisa , Federação Russa , África do SulRESUMO
Neglected diseases are infectious diseases that affect poor people of tropical countries. Drug resistance, lower availability of funds and research hinder the opportunities for the development of new drugs. The need for new drugs will persist until pathogens are eradicated. This calls for understanding the disease prognosis to initiate research for new drug targets and thus development of new drugs. As drug development is complex and expensive process, in silico drug development can aid in this regard by reducing time, effort and capital for the quest of a "better drug" for such neglected diseases. Recent knowledge about the genome and proteome has increased enthusiasm for the quest of new drug targets. One such potential target can be lipases which are involved in the lipid metabolism of pathogens. Lipases of pathogens have multitude of functions in many patho-physiological processes including virulence, transmission, life cycle development, modulation of host lipids and host immune responses. Thus the aim of this review is to describe the significance of lipases in the life cycle and pathogenesis of the pathogen and whether they can be used as drug targets. The development of research in this direction has also been brought forward. This may help in finding new drug targets for neglected disease.
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Descoberta de Drogas/métodos , Lipólise/efeitos dos fármacos , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/enzimologia , Animais , Humanos , Lipase/metabolismo , Terapia de Alvo Molecular , Doenças Negligenciadas/etiologiaAssuntos
Doenças Transmissíveis/etiologia , Suscetibilidade a Doenças/imunologia , Imunidade Inata , Doenças Negligenciadas/etiologia , Medicina Tropical , Biomarcadores , Doenças Transmissíveis/metabolismo , Interações Hospedeiro-Parasita , Interações Hospedeiro-Patógeno , Humanos , Doenças Negligenciadas/metabolismo , Clima Tropical , Medicina Tropical/tendênciasAssuntos
Doenças Musculares , Doenças Negligenciadas , Doenças Neuromusculares , Doenças Raras , França , Humanos , Pesquisa Interdisciplinar , Doenças Musculares/diagnóstico , Doenças Musculares/etiologia , Doenças Negligenciadas/diagnóstico , Doenças Negligenciadas/etiologia , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/etiologia , Doenças Neuromusculares/genética , Doenças Raras/diagnóstico , Doenças Raras/etiologia , Sociedades MédicasAssuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Transtornos do Espectro Alcoólico Fetal/prevenção & controle , Exposição Materna/efeitos adversos , Doenças Negligenciadas/prevenção & controle , Consumo de Bebidas Alcoólicas/epidemiologia , Inglaterra/epidemiologia , Feminino , Transtornos do Espectro Alcoólico Fetal/epidemiologia , Transtornos do Espectro Alcoólico Fetal/etiologia , Humanos , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/etiologia , Gravidez , PrevalênciaRESUMO
BACKGROUND: In Ethiopia, lymphatic filariasis and podoconiosis are the two neglected tropical diseases planned to be mapped together within the recently launched Ethiopian neglected tropical diseases master plan (2013-2015). However, other disorders cause tropical lymphedema, and this report aims to identify clinical epidemiological aspects of limb swelling in northern Ethiopia and to provide an algorithm orienting the clinical diagnosis. METHODS: Medical records of patients with lower limb elephantiasis attending the Italian Dermatological Centre of Mekele, Tigray capital city, over a 4-year period (2005-2009) were retrospectively analyzed. Nine variables were collected from the charts comprising demographic data, job, origin, literacy, clinical, histopathologic, microscopic, and cultural findings. RESULTS: Over a total of 511 patients, lymphedema resulted from trauma (40.7%), chronic venous insufficiency (12.5%), deep mycoses (10.8%), lymphatic filariasis (9.2%), elephantiasis nostras verrucosa (7.0%), tropical ulcer (6.3%), leprosy (4.9%), recurrent infections (3.1%), podoconiosis (1.8%), tuberculosis (1.0%), malignancy (1.3%), Kaposi's sarcoma (1.0%), leishmaniasis (0.2%), and neurofibromatosis (0.2%). CONCLUSIONS: Advanced-stage elephantiasis, chronic osteomyelitis, and podoconiosis not previously reported in Tigray were observed. Further epidemiological investigation and training programs addressed to healthcare providers at the peripheral level are needed to detect elephantiasis early, prevent disabilities, and improve patients' quality of life.
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Elefantíase/epidemiologia , Elefantíase/etiologia , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/etiologia , Adolescente , Adulto , Escolaridade , Elefantíase/diagnóstico , Filariose Linfática/diagnóstico , Filariose Linfática/epidemiologia , Etiópia/epidemiologia , Feminino , Humanos , Leishmaniose/complicações , Hanseníase/complicações , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Micoses/complicações , Doenças Negligenciadas/diagnóstico , Neurofibromatoses/complicações , Ocupações/estatística & dados numéricos , Estudos Retrospectivos , Sarcoma de Kaposi/complicações , Tuberculose/complicações , Insuficiência Venosa/complicações , Ferimentos e Lesões/complicações , Adulto JovemRESUMO
Buruli ulcer (BU), or Mycobacterium ulcerans infection, is a new emerging infectious disease which has been reported in over 33 countries worldwide. It has been noted not only in tropical areas, such as West Africa where it is most endemic, but also in moderate non-tropical climate areas, including Australia and Japan. Clinical presentation starts with a papule, nodule, plaque or edematous form which eventually leads to extensive skin ulceration. It can affect all age groups, but especially children aged between 5 and 15 years in West Africa. Multiple-antibiotic treatment has proven effective, and with surgical intervention at times of severity, it is curable. However, if diagnosis and treatment is delayed, those affected may be left with life-long disabilities. The disease is not yet fully understood, including its route of transmission and pathogenesis. However, due to recent research, several important features of the disease are now being elucidated. Notably, there may be undiagnosed cases in other parts of the world where BU has not yet been reported. Japan exemplifies the finding that awareness among dermatologists plays a key role in BU case detection. So, what about in other countries where a case of BU has never been diagnosed and there is no awareness of the disease among the population or, more importantly, among health professionals? This article will revisit BU, reviewing clinical features as well as the most recent epidemiological and scientific findings of the disease, to raise awareness of BU among dermatologists worldwide.
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Úlcera de Buruli/diagnóstico , Úlcera de Buruli/etiologia , Úlcera de Buruli/terapia , Doenças Transmissíveis Emergentes/diagnóstico , Doenças Transmissíveis Emergentes/etiologia , Doenças Transmissíveis Emergentes/terapia , Humanos , Doenças Negligenciadas/diagnóstico , Doenças Negligenciadas/etiologia , Doenças Negligenciadas/terapiaRESUMO
BACKGROUND: Elimination of blinding trachoma by 2020 can only be achieved if affected areas have effective control programs in place before the target date. Identifying risk factors for active disease that are amenable to intervention is important to successfully design such programs. Previous studies have linked sleeping by a cooking fire to trachoma in children, but not fully explored the mechanism and risks. We propose to determine the risk for active trachoma in children with exposure to cooking fires by severity of trachoma, adjusting for other known risk factors. METHODS: Complete census of 52 communities in Kongwa, Tanzania, was conducted to collect basic household characteristics and demographic information on each family member. Information on exposure to indoor cooking fires while the mother was cooking and while sleeping for each child was collected. 6656 randomly selected children ages 1-9 yrs were invited to a survey where both eyelids were graded for follicular (TF) and intense trachoma (TI) using the WHO simplified grading scheme. Ocular swab were taken to assess the presence of Chlamydia trachomatis. FINDINGS: 5240 (79%) of the invited children participated in the study. Overall prevalence for trachoma was 6·1%. Odds for trachoma and increased severity were higher in children sleeping without ventilation and a cooking fire in their room (TF OR = 1·81, 1·00-3·27 and TI OR 4·06, 1·96-8·42). Children with TF or TI who were exposed were more likely to have infection than children with TF or TI who were not exposed. There was no increased risk with exposure to a cooking fire while the mother was cooking. CONCLUSIONS: In addition to known risk factors for trachoma, sleeping by an indoor cooking fire in a room without ventilation was associated with active trachoma and appears to substantially increase the risk of intense inflammation.
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Poluição do Ar em Ambientes Fechados/efeitos adversos , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/etiologia , Fumaça/efeitos adversos , Tracoma/epidemiologia , Tracoma/etiologia , Criança , Pré-Escolar , Culinária , Pálpebras/patologia , Incêndios , Humanos , Lactente , Modelos Estatísticos , Prevalência , Fatores de Risco , Tanzânia/epidemiologiaRESUMO
Podoconiosis, mossy foot or endemic non-filarial elephantiasis, is a geochemical disease that causes lower limb lymphedema; it is directly related to walking barefoot over soils of volcanic origin, in areas with a high pluviometric annual index. It has a specific geographical distribution, affecting around 5% population in areas where it is endemic. It is debilitating and disfiguring disease, which frequently leads to social margination. Podoconiosis is totally preventable and, once a diagnosis is established, it may improve with simple therapeutic measures.
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Elefantíase , Doenças Negligenciadas , Diagnóstico Diferencial , Elefantíase/diagnóstico , Elefantíase/epidemiologia , Elefantíase/etiologia , Elefantíase/terapia , Saúde Global , Humanos , Doenças Negligenciadas/diagnóstico , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/etiologia , Doenças Negligenciadas/terapia , Fatores de RiscoRESUMO
Diverse aetiologies of viral and bacterial encephalitis are widely recognized as significant yet neglected public health issues in the Mekong region. A robust analysis of the corresponding health burden is lacking. We retrieved 75 articles on encephalitis in the region published in English or in French from 1965 through 2011. Review of available data demonstrated that they are sparse and often derived from hospital-based studies with significant recruitment bias. Almost half (35 of 75) of articles were on Japanese encephalitis virus (JEV) alone or associated with dengue. In the Western Pacific region the WHO reported 30,000-50,000 annual JEV cases (15,000 deaths) between 1966 and 1996 and 4,633 cases (200 deaths) in 2008, a decline likely related to the introduction of JEV vaccination in China, Vietnam, or Thailand since the 1980s. Data on dengue, scrub typhus and rabies encephalitis, among other aetiologies, are also reviewed and discussed. Countries of the Mekong region are undergoing profound demographic, economic and ecological change. As the epidemiological aspects of Japanese encephalitis (JE) are transformed by vaccination in some countries, highly integrated expert collaborative research and objective data are needed to identify and prioritize the human health, animal health and economic burden due to JE and other pathogens associated with encephalitides.
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Encefalite Viral/epidemiologia , Encefalite Viral/etiologia , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/etiologia , Animais , China/epidemiologia , Controle de Doenças Transmissíveis/métodos , Humanos , Tailândia/epidemiologia , Vietnã/epidemiologiaRESUMO
A esporotricose é uma micose subcutânea de distribuição mundial, sendo observada em surtos de proporções variáveis, com predominância em áreas de clima temperado e tropical. Algumas áreas de endemicidade já foram relatadas. No Brasil, seus agentes etiológicos encontraram não só condições climáticas e estruturais ideais, mas também fontes de infecções extremamente eficientes. Nas últimas décadas, o país tem observado um aumento exponencial no número de casos de esporotricose humana e animal. Esse aumento e o surgimento de resistência aos antifúngicos tornam a situação alarmante. Apesar de essa epidemia se perpetuar há anos, existem poucas políticas de saúde no Brasil para o controle dos casos de esporotricose humana e animal, principalmente na atenção primária à saúde. Assim, intervenções sociais, ambientais e populacionais devem ser feitas para conter essa epidemia negligenciada.
Sporotrichosis is a subcutaneous mycosis with a worldwide distribution, which has been observed in outbreaks of variable proportions in all continents, with predominance in temperate and tropical climate zones. Some areas of endemicity have already been reported. In Brazil, its etiological agents found not only ideal climatic and structural conditions, but also extremely efficient sources of infections. In the last decades, the country has suffered an exponential increase in the number of human and animal cases of sporotrichosis. This increase, combined with the emergence of antifungal resistance makes the situation alarming. Although this epidemic has been perpetuating for years, there are few health policies in Brazil to control it/the disease, especially in primary health care. Therefore, social, environmental and population-based interventions should be organized in order to contain this neglected epidemic.