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1.
Clin Microbiol Rev ; 37(2): e0003423, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38690871

RESUMO

SUMMARYIn 2023, the World Health Organization designated eumycetoma causative agents as high-priority pathogens on its list of fungal priority pathogens. Despite this recognition, a comprehensive understanding of these causative agents is lacking, and potential variations in clinical manifestations or therapeutic responses remain unclear. In this review, 12,379 eumycetoma cases were reviewed. In total, 69 different fungal species were identified as causative agents. However, some were only identified once, and there was no supporting evidence that they were indeed present in the grain. Madurella mycetomatis was by far the most commonly reported fungal causative agent. In most studies, identification of the fungus at the species level was based on culture or histology, which was prone to misidentifications. The newly used molecular identification tools identified new causative agents. Clinically, no differences were reported in the appearance of the lesion, but variations in mycetoma grain formation and antifungal susceptibility were observed. Although attempts were made to explore the differences in clinical outcomes based on antifungal susceptibility, the lack of large clinical trials and the inclusion of surgery as standard treatment posed challenges in drawing definitive conclusions. Limited case series suggested that eumycetoma cases caused by Fusarium species were less responsive to treatment than those caused by Madurella mycetomatis. However, further research is imperative for a comprehensive understanding.


Assuntos
Antifúngicos , Micetoma , Micetoma/microbiologia , Micetoma/tratamento farmacológico , Micetoma/diagnóstico , Humanos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Madurella/efeitos dos fármacos , Resultado do Tratamento
2.
Proc Biol Sci ; 291(2024): 20240449, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38864320

RESUMO

The WHO aims to eliminate schistosomiasis as a public health problem by 2030. However, standard morbidity measures poorly correlate to infection intensities, hindering disease monitoring and evaluation. This is exacerbated by insufficient evidence on Schistosoma's impact on health-related quality of life (HRQoL). We conducted community-based cross-sectional surveys and parasitological examinations in moderate-to-high Schistosoma mansoni endemic communities in Uganda. We calculated parasitic infections and used EQ-5D instruments to estimate and compare HRQoL utilities in these populations. We further employed Tobit/linear regression models to predict HRQoL determinants. Two-thirds of the 560 participants were diagnosed with parasitic infection(s), 49% having S. mansoni. No significant negative association was observed between HRQoL and S. mansoni infection status/intensity. However, severity of pain urinating (ß = -0.106; s.e. = 0.043) and body swelling (ß = -0.326; s.e. = 0.005), increasing age (ß = -0.016; s.e. = 0.033), reduced socio-economic status (ß = 0.128; s.e. = 0.032), and being unemployed predicted lower HRQoL. Symptom severity and socio-economic status were better predictors of short-term HRQoL than current S. mansoni infection status/intensity. This is key to disentangling the link between infection(s) and short-term health outcomes, and highlights the complexity of correlating current infection(s) with long-term morbidity. Further evidence is needed on long-term schistosomiasis-associated HRQoL, health and economic outcomes to inform the case for upfront investments in schistosomiasis interventions.


Assuntos
Qualidade de Vida , Schistosoma mansoni , Esquistossomose mansoni , Esquistossomose mansoni/epidemiologia , Uganda/epidemiologia , Humanos , Estudos Transversais , Feminino , Masculino , Animais , Schistosoma mansoni/fisiologia , Adulto , Adolescente , Criança , Pessoa de Meia-Idade , Adulto Jovem
3.
Proc Natl Acad Sci U S A ; 118(11)2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33836584

RESUMO

Temperature constrains the transmission of many pathogens. Interventions that target temperature-sensitive life stages, such as vector control measures that kill intermediate hosts, could shift the thermal optimum of transmission, thereby altering seasonal disease dynamics and rendering interventions less effective at certain times of the year and with global climate change. To test these hypotheses, we integrated an epidemiological model of schistosomiasis with empirically determined temperature-dependent traits of the human parasite Schistosoma mansoni and its intermediate snail host (Biomphalaria spp.). We show that transmission risk peaks at 21.7 °C (Topt ), and simulated interventions targeting snails and free-living parasite larvae increased Topt by up to 1.3 °C because intervention-related mortality overrode thermal constraints on transmission. This Topt shift suggests that snail control is more effective at lower temperatures, and global climate change will increase schistosomiasis risk in regions that move closer to Topt Considering regional transmission phenologies and timing of interventions when local conditions approach Topt will maximize human health outcomes.


Assuntos
Biomphalaria/fisiologia , Biomphalaria/parasitologia , Schistosoma mansoni , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/transmissão , Animais , Interações Hospedeiro-Parasita , Humanos , Temperatura
4.
Molecules ; 29(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338378

RESUMO

Repurposing is a universal mechanism for innovation, from the evolution of feathers to the invention of Velcro tape. Repurposing is particularly attractive for drug development, given that it costs more than a billion dollars and takes longer than ten years to make a new drug from scratch. The COVID-19 pandemic has triggered a large number of drug repurposing activities. At the same time, it has highlighted potential pitfalls, in particular when concessions are made to the target product profile. Here, we discuss the pros and cons of drug repurposing for infectious diseases and analyze different ways of repurposing. We distinguish between opportunistic and rational approaches, i.e., just saving time and money by screening compounds that are already approved versus repurposing based on a particular target that is common to different pathogens. The latter can be further distinguished into divergent and convergent: points of attack that are divergent share common ancestry (e.g., prokaryotic targets in the apicoplast of malaria parasites), whereas those that are convergent arise from a shared lifestyle (e.g., the susceptibility of bacteria, parasites, and tumor cells to antifolates due to their high rate of DNA synthesis). We illustrate how such different scenarios can be capitalized on by using examples of drugs that have been repurposed to, from, or within the field of anti-infective chemotherapy.


Assuntos
COVID-19 , Doenças Transmissíveis , Animais , Humanos , Reposicionamento de Medicamentos , Pandemias , Doenças Transmissíveis/tratamento farmacológico , Bactérias
5.
Molecules ; 29(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38675665

RESUMO

In the search for new bioactive agents against the infectious pathogen responsible for the neglected tropical disease (NTD) mycetoma, we tested a collection of 27 essential oils (EOs) in vitro against Madurella mycetomatis, the primary pathogen responsible for the fungal form of mycetoma, termed eumycetoma. Among this series, the EO of Santalum album (Santalaceae), i.e., East Indian sandalwood oil, stood out prominently with the most potent inhibition in vitro. We, therefore, directed our research toward 15 EOs of Santalum species of different geographical origins, along with two samples of EOs from other plant species often commercialized as "sandalwood oils". Most of these EOs displayed similar strong activity against M. mycetomatis in vitro. All tested oils were thoroughly analyzed by GC-QTOF MS and most of their constituents were identified. Separation of the sandalwood oil into the fractions of sesquiterpene hydrocarbons and alcohols showed that its activity is associated with the sesquiterpene alcohols. The major constituents, the sesquiterpene alcohols (Z)-α- and (Z)-ß-santalol were isolated from the S. album oil by column chromatography on AgNO3-coated silica. They were tested as isolated compounds against the fungus, and (Z)-α-santalol was about two times more active than the ß-isomer.


Assuntos
Madurella , Micetoma , Óleos Voláteis , Óleos de Plantas , Santalum , Sesquiterpenos , Madurella/efeitos dos fármacos , Óleos de Plantas/farmacologia , Óleos de Plantas/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Micetoma/microbiologia , Micetoma/tratamento farmacológico , Santalum/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Antifúngicos/farmacologia , Antifúngicos/química , Testes de Sensibilidade Microbiana
6.
Parasite Immunol ; 45(6): e12981, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37038837

RESUMO

Schistosomiasis affects nearly 240 million people in predominately low- and middle-income countries and ranks second in the number of cases and socio-economic burden among all parasitic diseases. Despite the enormous burden posed by schistosomes, our understanding of how schistosomiasis impacts infected human tissues remains limited. Intestinal schistosomiasis in animal models leads to goblet cell hyperplasia, likely increasing mucus production and reflecting an intestinal type 2 immune response. However, it is unknown whether these same changes occur in schistosome-infected humans. Using immunofluorescence and light microscopy, we compared the abundance and morphology of goblet cells in patients diagnosed with schistosomiasis to uninfected controls. The mucin-containing vesicles in goblet cells from schistosome-infected patients were significantly larger (hypertrophic) than uninfected individuals, although goblet cell hyperplasia was absent in chronic human schistosomiasis. In addition, we examined tuft cells in the large intestinal epithelium of control and schistosome-infected patients. Tuft cell numbers expand during helminth infection in mice, but these cells have not been characterized in human parasite infections. We found no evidence of tuft cell hyperplasia during human schistosome infection. Thus, our study provides novel insight into schistosome-associated changes to the intestinal epithelium in humans, suggesting an increase in mucus production by large intestinal goblet cells but relatively minor effects on tuft cell numbers.


Assuntos
Esquistossomose , Humanos , Animais , Camundongos , Hiperplasia/metabolismo , Hiperplasia/patologia , Células Caliciformes/metabolismo , Mucosa Intestinal/metabolismo , Mucinas/metabolismo
7.
Parasitology ; 150(11): 1052-1062, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37927101

RESUMO

Effective supply chain management is a critical pillar of well-functioning health systems ensuring that medical commodities reach those in need. In Liberia, the national neglected tropical disease (NTD) programme supports health systems strengthening for case management of NTDs. Integration of NTD commodities into the national health system supply chain is central to the integrated approach; however, there is minimal evidence on enablers and barriers. Drawing on qualitative evaluation data, we illustrate that perceived benefits and strengths to integrating NTD commodities into the supply chain include leveraged storage and management capacities capitalized at lower system levels; the political will to integrate based on cost-saving and capacity strengthening potential and positive progress integrating paper-based reporting tools. Challenges remain, specifically the risk of reliance on donor funding; difficulty in accessing commodities due to bureaucratic bottlenecks; lack of inclusion of NTD commodities within electronic data tools and poor coordination leading to an inability to meet demand. Collectively, the negative consequences of ineffective integration of NTD commodities into the supply chain has a detrimental impact on health workers (including community health workers) unable to deliver the quality of care to patients. Trust between affected populations and the health system is compromised when treatments are unavailable.


Assuntos
Doenças Negligenciadas , Medicina Tropical , Humanos , Libéria , Doenças Negligenciadas/prevenção & controle
8.
J Infect Chemother ; 29(8): 800-802, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37075979

RESUMO

Leptospirosis, a zoonotic disease characterized by a spectrum of influenza-like symptoms, can manifest as severe cases so called Weil's disease. Early diagnosis and treatment are crucial to avoid the potentially fatal course of the disease. Within 24 hours of the initial administration of antibiotics, patients may experience the Jarisch-Herxheimer reaction (JHR), characterized by chills, fever, hypotension, and impaired consciousness. The Okinawa Prefecture, where our hospital is situated, boasts the highest incidence rate of leptospirosis among all regions in Japan. This reports our encounter with the initial leptospirosis case after a period of 16 years within the Okinawa Prefecture. This case exhibited JHR and required the utilization of noradrenaline (NA). Despite evidence indicating that JHR does not correlate with mortality, we contend that diagnosis of Weil's disease necessitates admission to an intensive care unit (ICU) and vigilant monitoring for JHR, as it may result in impairment of general condition and fatal outcome, as observed in our case.


Assuntos
Leptospirose , Doença de Weil , Humanos , Doença de Weil/tratamento farmacológico , Leptospirose/diagnóstico , Leptospirose/tratamento farmacológico , Antibacterianos/efeitos adversos , Norepinefrina/uso terapêutico , Japão/epidemiologia
9.
BMC Public Health ; 23(1): 1834, 2023 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-37730592

RESUMO

Community engagement strategies provide tools for sustainable vector-borne disease control. A previous cluster randomized control trial engaged nine intervention communities in seven participatory activities to promote management of the domestic and peri-domestic environment to reduce risk factors for vector-borne Chagas disease. This study aims to assess the adoption of this innovative community-based strategy, which included chickens' management, indoor cleaning practices, and domestic rodent infestation control, using concepts from the Diffusion of Innovations Theory. We used questionnaires and semi-structured interviews to understand perceptions of knowledge gained, intervention adoption level, innovation attributes, and limiting or facilitating factors for adoption. The analysis process focused on five innovation attributes proposed by the Diffusion of Innovations Theory: relative advantage, compatibility, complexity, trialability, and observability. Rodent management was highly adopted by participants, as it had a relative advantage regarding the use of poison and was compatible with local practices. The higher complexity was reduced by offering several types of trapping systems and having practical workshops allowed trialability. Observability was limited because the traps were indoors, but information and traps were shared with neighbors. Chicken management was not as widely adopted due to the higher complexity of the method, and lower compatibility with local practices. Using the concepts proposed by the Diffusion of Innovations Theory helped us to identify the enablers and constraints in the implementation of the Chagas vector control strategy. Based on this experience, community engagement and intersectoral collaboration improve the acceptance and adoption of novel and integrated strategies to improve the prevention and control of neglected diseases.


Assuntos
Galinhas , Colaboração Intersetorial , Animais , Humanos , Conhecimento , Doenças Negligenciadas , Fatores de Risco
10.
Parasitol Res ; 123(1): 41, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38095735

RESUMO

Schistosomiasis remains a major public health concern affecting approximately 12 million people in the Philippines due to inadequate information about the disease and limited prevention and control efforts. Schistosoma japonicum, one of the causative agents of the disease, requires an amphibious snail Oncomelania hupensis quadrasi (O. h. quadrasi) to complete its life cycle. Using the geographical information system (GIS) and maximum entropy (MaxEnt) algorithm, this study aims to predict the potential high-risk habitats of O. h. quadrasi driven by environmental factors in the Philippines. Based on the bioclimatic determinants, a very high-performance model was generated (AUC = 0.907), with the mean temperature of the driest quarter (25.3%) contributing significantly to the prevalence of O. h. quadrasi. Also, the snail vector has a high focal distribution, preferring areas with a pronounced wet season and high precipitation throughout the year. However, the findings provided evidence for snail adaptation to different environmental conditions. High suitability of snail habitats was found in Quezon, Camarines Norte, Camarines Sur, Albay, Sorsogon, Northern Samar, Eastern Samar, Leyte, Bohol, Surigao del Norte, Surigao del Sur, Agusan del Norte, Davao del Norte, North Cotabato, Lanao del Norte, Misamis Occidental, and Zamboanga del Sur. Furthermore, snail habitat establishment includes natural and man-made waterlogged areas, with the progression of global warming and climate change predicted to be drivers of increasing schistosomiasis transmission zones in the country.


Assuntos
Gastrópodes , Schistosoma japonicum , Esquistossomose , Animais , Humanos , Filipinas/epidemiologia , Entropia , Ecossistema , China
11.
Health Res Policy Syst ; 21(1): 29, 2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37055758

RESUMO

BACKGROUND: Neglected tropical diseases (NTDs) are associated with high levels of morbidity and disability as a result of stigma and social exclusion. To date, the management of NTDs has been largely biomedical. Consequently, ongoing policy and programme reform within the NTD community is demanding the development of more holistic disease management, disability and inclusion (DMDI) approaches. Simultaneously, integrated, people-centred health systems are increasingly viewed as essential to ensure the efficient, effective and sustainable attainment of Universal Health Coverage. Currently, there has been minimal consideration of the extent to which the development of holistic DMDI strategies are aligned to and can support the development of people-centred health systems. The Liberian NTD programme is at the forefront of trying to establish a more integrated, person-centred approach to the management of NTDs and provides a unique learning site for health systems decision makers to consider how shifts in vertical programme delivery can support overarching systems strengthening efforts that are designed to promote the attainment of health equity. METHODS: We use a qualitative case study approach to explore how policy and programme reform of the NTD programme in Liberia supports systems change to enable the development of integrated people-centred services. RESULTS: A cumulation of factors, catalysed by the shock to the health system presented by the Ebola epidemic, created a window of opportunity for policy change. However, programmatic change aimed at achieving person-centred practice was more challenging. Deep reliance on donor funding for health service delivery in Liberia limits the availability of flexible funding, and the ongoing funding prioritization towards specific disease conditions limits flexibility in health systems design that can shape more person-centred care. CONCLUSION: Sheikh et al.'s four key aspects of people centred health systems, that is, (1) putting peoples voices and needs first; (2) people centredness in service delivery; (3) relationships matter: health systems as social institutions; and (4) values drive people centred health systems, enable the illumination of varying push and pull factors that can facilitate or hinder the alignment of DMDI interventions with the development of people-centred health systems to support disease programme integration and the attainment of health equity.


Assuntos
Medicina Tropical , Humanos , Libéria , Doenças Negligenciadas/terapia
12.
Chem Biodivers ; 20(5): e202300151, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37067830

RESUMO

Eumycetoma, the fungal form of the neglected tropical disease mycetoma, is a crippling infectious disease with low response rates to currently available antifungal drugs. In this study, a series of natural naphthoquinones and anthraquinones was evaluated for their activity against Madurella mycetomatis, which is the most common causative agent of eumycetoma. The metabolic activity of Madurella mycetomatis as well as the viability of Galleria mellonella larvae upon treatment with quinones was investigated. Several hydroxy-substituted naphthoquinones exhibited activity against Madurella mycetomatis. In particular, naphthazarin (5,8-dihydroxy-1,4-naphthoquinone) was identified as a considerably active antifungal compound against Madurella mycetomatis (IC50 =1.4 µM), while it showed reduced toxicity to Galleria mellonella larvae, which is a well-established in vivo invertebrate model for mycetoma drug studies.


Assuntos
Besouros , Madurella , Mariposas , Micetoma , Naftoquinonas , Animais , Antifúngicos/farmacologia , Micetoma/tratamento farmacológico , Micetoma/microbiologia , Antraquinonas/farmacologia , Larva , Naftoquinonas/farmacologia
13.
Wilderness Environ Med ; 34(3): 366-371, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37179190

RESUMO

Snakebite envenoming is a neglected tropical disease disproportionately affecting the rural and marginalized population in low-middle-income countries. The saw-scaled viper (Echis carinatus) is a clinically important snake that causes serious morbidity and mortality in the Indian subcontinent. Even though it is within the so-called big-four snakes against which polyvalent antivenom is available throughout India, reports of antivenom ineffectiveness are emerging in saw-scaled viper envenoming, especially around Jodhpur, Rajasthan, India. This case report highlights a patient with saw-scaled viper envenoming with an ineffective antivenom response complicated by acute kidney injury as well as local and systemic bleeding complications, which subsequently resulted in a pelvic hematoma that compressed the lumbosacral nerves, causing lower-limb weakness and sensory deficits. He was successfully managed with hematoma aspiration and supportive care. This case brings into focus the challenges of managing saw-scaled viper envenoming in this region with antivenom ineffectiveness, resulting in delayed and significant coagulopathy and its complications leading to prolonged hospital stay and morbidity. Our report spotlights less emphasized aspects of long-term morbidity in snakebite survivors, such as loss of working days and productivity. We also highlight the need for an organized system of long-term follow-up of snakebite survivors to screen for possible complications and manage them early.


Assuntos
Mordeduras de Serpentes , Viperidae , Masculino , Animais , Antivenenos/uso terapêutico , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/terapia , Mordeduras de Serpentes/epidemiologia , Venenos de Víboras , Índia
14.
J Infect Dis ; 225(6): 994-1004, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33034349

RESUMO

BACKGROUND: To eliminate trachoma as a public health problem, the World Health Organization recommends the SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. As part of the SAFE strategy in the Amhara Region, Ethiopia, the Trachoma Control Program distributed >124 million doses of antibiotics between 2007 and 2015. Despite this, trachoma remained hyperendemic in many districts and a considerable level of Chlamydia trachomatis (Ct) infection was evident. METHODS: We utilized residual material from Abbott m2000 Ct diagnostic tests to sequence 99 ocular Ct samples from Amhara and investigated the role of Ct genomic variation in continued transmission of Ct. RESULTS: Sequences were typical of ocular Ct at the whole-genome level and in tissue tropism-associated genes. There was no evidence of macrolide resistance in this population. Polymorphism around the ompA gene was associated with village-level trachomatous inflammation-follicular prevalence. Greater ompA diversity at the district level was associated with increased Ct infection prevalence. CONCLUSIONS: We found no evidence for Ct genomic variation contributing to continued transmission of Ct after treatment, adding to evidence that azithromycin does not drive acquisition of macrolide resistance in Ct. Increased Ct infection in areas with more ompA variants requires longitudinal investigation to understand what impact this may have on treatment success and host immunity.


Assuntos
Gonorreia , Doenças do Recém-Nascido , Tracoma , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Chlamydia trachomatis/genética , Farmacorresistência Bacteriana/genética , Etiópia/epidemiologia , Genômica , Gonorreia/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Macrolídeos/uso terapêutico , Prevalência , Tracoma/tratamento farmacológico , Tracoma/epidemiologia , Tracoma/prevenção & controle
15.
Med Mycol ; 60(2)2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35064672

RESUMO

Eumycetoma is a neglected tropical disease, and Madurella mycetomatis, the most common causative agent of this disease forms black grains in hosts. Melanin was discovered to be one of the constituents in grains. Melanins are hydrophobic, macromolecular pigments formed by oxidative polymerisation of phenolic or indolic compounds. M. mycetomatis was previously known to produce DHN-melanin and pyomelanin in vitro. These melanin was also discovered to decrease M. mycetomatis's susceptibility to antifungals itraconazole and ketoconazole in vitro. These findings, however, have not been confirmed in vivo. To discover the melanin biosynthesis pathways used by M. mycetomatis in vivo and to determine if inhibiting melanin production would increase M. mycetomatis's susceptibility to itraconazole, inhibitors targeting DHN-, DOPA- and pyomelanin were used. Treatment with DHN-melanin inhibitors tricyclazole, carpropamid, fenoxanil and DOPA-melanin inhibitor glyphosate in M. mycetomatis infected Galleria mellonella larvae resulted in presence of non-melanized grains. Our finding suggested that M. mycetomatis is able to produce DOPA-melanin in vivo. Inhibiting DHN-melanin with carpropamid in combination with the antifungal itraconazole also significantly increased larvae survival. Our results suggested that combination treatment of antifungals and melanin inhibitors can be an alternative treatment strategy that can be further explored. Since the common black-grain eumycetoma causing agents uses similar melanin biosynthesis pathways, this strategy may be applied to them and other eumycetoma causative agents. LAY SUMMARY: Melanin protects fungi from environmental stress and antifungals. We have discovered that Madurella mycetomatis produces DHN-, pyomelanin and DOPA-melanin in vivo. Inhibiting M. mycetomatis DHN-melanin biosynthesis increases therapeutic value of the antifungal itraconazole in vivo.


Assuntos
Madurella , Micetoma , Animais , Antifúngicos/farmacologia , Di-Hidroxifenilalanina/análogos & derivados , Itraconazol/farmacologia , Micetoma/tratamento farmacológico , Micetoma/veterinária
16.
Parasitology ; 149(1): 1-9, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34694217

RESUMO

Human toxocariasis is a neglected tropical disease, which is actually global in distribution and has a significant impact on global public health. The infection can lead to several serious conditions in humans, including allergic, ophthalmic and neurological disorders such as epilepsy. It is caused by the common roundworm species Toxocara canis and Toxocara cati, with humans becoming accidentally infected via the ingestion of eggs or larvae. Toxocara eggs are deposited on the ground when infected dogs, cats and foxes defecate, with the eggs contaminating crops, grazing pastures, and subsequently food animals. However, transmission of Toxocara to humans via food consumption has received relatively little attention in the literature. To establish the risks that contaminated food poses to the public, a renewed research focus is required. This review discusses what is currently known about food-borne Toxocara transmission, highlighting the gaps in our understanding that require further attention, and outlining some potential preventative strategies which could be employed to safeguard consumer health.


Assuntos
Doenças do Sistema Nervoso , Toxocara canis , Toxocaríase , Animais , Encéfalo , Cães , Humanos , Toxocara , Toxocaríase/epidemiologia , Toxocaríase/prevenção & controle , Toxocaríase/transmissão , Zoonoses
17.
Bioorg Chem ; 120: 105621, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35074578

RESUMO

Biology-Oriented Drug Synthesis (BIODS) deals with the simple chemical transformations on the commercially available drugs in order to enhance their new and diversified pharmacological profile. It opens new avenues for the rapid development of drug candidates for neglected tropical diseases (NTDs). Leishmaniasis is one of the NTDs which spread by the bite of sandflies (plebotomine). It ranges from cutaneous self-healing leishmaniasis to life threatening visceral leishmaniasis, known as kala-azar. The current treatment options include the use of pentamidine, miltefosine, and amphotericin B drugs. Unfortunately, all currently available drugs are associated with adverse effects, such as severe nephron- and cardiotoxicity, pancreatitis, and hepatotoxicity. This warrants the development of new drugs against leishmaniasis. Moreover, emergence of resistance against the current medications further worsens the conditions. With this objective, new N, N'-disubstituted benzylamine derivatives of ampyrone (4-aminoantipyrine) were synthesized by using ultrasonication, and microwave assistance. All derivatives were found to be new, except 1, 4, and 11. All the compounds were evaluated for their anti-leishmanial activity, and cellular cytotoxicity. Among them, compounds 4, 5, 8, and 9 showed a significant anti-leishmanial activity in vitro, in comparison to standard drug, miltefosine (IC50 = 25.78 ± 0.2 µM). These compounds were also docked against various metabolic enzymes to predict their interactions and mechanism of action, and were found to act via targeting important enzymes of various metabolic pathways.


Assuntos
Antiprotozoários , Leishmania donovani , Leishmaniose Visceral , Leishmaniose , Ampirona , Antiprotozoários/química , Benzilaminas/farmacologia , Biologia , Humanos , Leishmaniose/tratamento farmacológico , Leishmaniose Visceral/tratamento farmacológico , Micro-Ondas
18.
Dermatol Ther ; 35(9): e15699, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35808917

RESUMO

Cutaneous leishmaniasis (CL) is a skin disease caused by intracellular protozoa, which is endemic in Iran. The goal of this study was to compare biophysical characteristics in CL lesions with uninvolved skin. Stratum corneum hydration, transepidermal water loss, surface friction, pH, sebum, melanin, erythema, temperature, elasticity parameters (R0, R2, and R5), thickness and echo-density of epidermis and dermis were measured on the active erythematous indurated part of a typical CL lesion in 20 patients, and compared with the same location on the other side of the body as control. Paired t-test was used for statistical analyses and a p < 0.05 was considered significant. Melanin content, R2 and echo-density of dermis were significantly lower, whereas transepidermal water loss, friction index, pH, erythema index, temperature, and the thickness of dermis were significantly higher in CL lesions. There was no significant difference in stratum corneum hydration, sebum, R0, R5, thickness of epidermis, and density of epidermis between CL and normal skin. CL lesions are characterized by certain changes in biophysical and ultrasonographic properties, which are mostly correlated with histological features. These changes are likely to be useful in the non-invasive early detection of CL and also as treatment outcome measures for clinical trials of new treatment modalities for CL in the future.


Assuntos
Leishmaniose Cutânea , Melaninas , Eritema , Humanos , Leishmaniose Cutânea/diagnóstico por imagem , Leishmaniose Cutânea/patologia , Avaliação de Resultados em Cuidados de Saúde , Pele/diagnóstico por imagem , Pele/patologia , Água
19.
BMC Health Serv Res ; 22(1): 792, 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35717193

RESUMO

BACKGROUND: Recent evidence suggests that community-wide mass drug administration (MDA) may interrupt the transmission of soil-transmitted helminths (STH), a group of intestinal worms that infect 1.5 billion individuals globally. Although current operational guidelines provide best practices for effective MDA delivery, they do not describe which activities are most essential for achieving high coverage or how they work together to produce effective intervention delivery. We aimed to identify the various packages of influential intervention delivery activities that result in high coverage of community-wide MDA for STH in Benin, India, and Malawi. METHODS: We applied coincidence analysis (CNA), a novel cross-case analytical method, to process mapping data as part of the implementation science research of the DeWorm3 Project, a Hybrid Type 1 cluster randomized controlled trial assessing the feasibility of interrupting the transmission of STH using bi-annual community-wide MDA in Benin, India, and Malawi. Our analysis aimed to identify any necessary and/or sufficient combinations of intervention delivery activities (i.e., implementation pathways) that resulted in high MDA coverage. Activities were related to drug supply chain, implementer training, community sensitization strategy, intervention duration, and implementation context. We used pooled implementation data from three sites and six intervention rounds, with study clusters serving as analytical cases (N = 360). Secondary analyses assessed differences in pathways across sites and over intervention rounds. RESULTS: Across all three sites and six intervention rounds, efficient duration of MDA delivery (within ten days) singularly emerged as a common and fundamental component for achieving high MDA coverage when combined with other particular activities, including a conducive implementation context, early arrival of albendazole before the planned start of MDA, or a flexible community sensitization strategy. No individual activity proved sufficient by itself for producing high MDA coverage. We observed four possible overall models that could explain effective MDA delivery strategies, all which included efficient duration of MDA delivery as an integral component. CONCLUSION: Efficient duration of MDA delivery uniquely stood out as a highly influential implementation activity for producing high coverage of community-wide MDA for STH. Effective MDA delivery can be achieved with flexible implementation strategies that include various combinations of influential intervention components.


Assuntos
Anti-Helmínticos , Helmintíase , Helmintos , Animais , Anti-Helmínticos/uso terapêutico , Helmintíase/tratamento farmacológico , Helmintíase/epidemiologia , Helmintíase/prevenção & controle , Humanos , Administração Massiva de Medicamentos/métodos , Prevalência , Solo/parasitologia
20.
Parasitol Res ; 121(1): 1-10, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34993634

RESUMO

Trichuriasis is one of the most common soil-transmitted helminth (STH) infections, affecting populations globally. The condition is particularly prevalent in tropical and subtropical areas with low levels of sanitation and poor living conditions. The objective of this systematic review and meta-analysis was to evaluate the prevalence of Trichuris trichiura infection in Asia at the country and region level. Multiple databases/academic search engines (Web of Science, PubMed, ProQuest, Scopus, and Google Scholar) were searched for literature on T. trichiura prevalence in Asia published through January 2021. Pooled prevalence was determined using the meta-package in R (version 3.6.1). Out of 13,836 articles, 226 studies (5,439,500 individuals) from 26 countries met the inclusion criteria. Of the 226 studies, 151 were community-based studies that included individuals across the age spectrum, while 75 studies focused on school children (typically in the 5-16 years age range). The overall T. trichiura pooled prevalence was 15.3% (95% CI: 12.4-19.1%), with a pooled prevalence of 13.3% (95% CI: 10.0-17.1%) for the community studies and 20.9% (95% CI: 14.7-27.9%) for the studies only including school children. For studies including all age groups, individuals in the 1-15 years age group had the highest pooled prevalence at 23.4% (95% CI: 1.7-49.4%). There was a significant difference found in overall pooled prevalence by sex (p < 0.001) and community type (rural versus urban) (p < 0.001). Although prevalence appears to be decreasing, study findings suggest that T. trichiura infection continues to be a public health problem in Asia. Therefore, control programs focused on at-risk individuals in endemic areas are needed.


Assuntos
Ascaríase , Helmintíase , Tricuríase , Adolescente , Animais , Ascaríase/epidemiologia , Ascaris lumbricoides , Ásia , Criança , Pré-Escolar , Fezes , Helmintíase/epidemiologia , Humanos , Lactente , Prevalência , Saneamento , Solo , Tricuríase/epidemiologia , Trichuris
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