Leptospirosis: predictores de mala evolución clínica en pacientes hospitalizados, 25 años de experiencia / Leptospirosis: predictors of poor outcomes in hospitalized patients, 25 years of experience

Introducción: La leptospirosis es una zoonosis que cons-tituye un problema emergente de salud pública. La insufi-ciencia renal, plaquetopenia y compromiso respiratorio se describen como predictores de mortalidad.Objetivos: Describir características clínicas, radiológicas y de laboratorio de individuos hospitalizados por leptos-pirosis y evaluar los predictores de mala evolución clínica (MEC).Materiales y métodos: Estudio de cohorte de inclusión ambispectiva de pacientes con leptospirosis internados en un hospital de la ciudad de Santa Fe entre 1997 y 2022. Se definió MEC como la admisión a Unidad de Cuidados Intensivos (UCI), requerimiento de asistencia respiratoria mecánica (ARM) y/o muerte. Se utilizaron las pruebas de Chi2, test T de Student o la U de Mann-Whitney, según co-rrespondiera. Se construyó una regresión logística binaria con las variables con p<0,05.Resultados: 101 pacientes, 87,1% (n=88) hombres, media-na de edad de 29 (RIC 20-44) años. La fiebre fue el síntoma más frecuente [83,2% (n=84)], seguido del compromiso di-gestivo [62,4% (n=63)]. Las alteraciones de laboratorio más frecuentes fueron: eritrosedimentación elevada [91,9% (n=79)] y leucocitosis [61% (n=61)]. Se observó MEC en el 25,7% (n=26). El 25,7% (n=26) fue admitido en UCI, el 13,9% (n=14) requirió ARM y el 5% (n=5) falleció. La presencia de plaquetopenia (OR=13,3, IC95% 2-80), las alteraciones en la radiografía de tórax (OR=33,5, IC95% 5-225) y la ausencia de cefalea (OR=6,8, IC95% 1-32) fueron predictores inde-pendientes de MEC.Conclusiones: En concordancia con la bibliografía, la afec-tación pulmonar y plaquetopenia son factores de riesgo para la mala evolución clínica. En nuestra serie, la cefalea constituyó un síntoma protector

Introduction: Leptospirosis is an emerging zoonotic di-sease that poses a public health problem. Renal failu-re, thrombocytopenia, and respiratory involvement have been described as predictors of mortality.Objectives: To describe the clinical, radiological, and la-boratory characteristics of hospitalized individuals with leptospirosis and evaluate predictors of poor clinical outcomes (PCO).Materials and methods: A prospective cohort study was conducted including patients with leptospirosis admit-ted to a hospital in the city of Santa Fe between 1997 and 2022. PCO was defined as admission to the Intensive Care Unit (ICU), requirement for mechanical respiratory assistance (MRA), and/or death. The chi-square test, Student>s t-test, or Mann-Whitney U test were used as appropriate. A binary logistic regression was performed with variables having p<0.05.Results: Out of the 101 patients included, 87.1% (n=88) were male, with a median age of 29 (IQR 20-44) years. Fever was the most common symptom [83.2% (n=84)], followed by digestive involvement [62.4% (n=63)]. The most frequent laboratory abnormalities were elevated erythrocyte sedimentation rate [91.9% (n=79)] and leuko-cytosis [61% (n=61)]. PCO was observed in 25.7% (n=26) of patients, with 25.7% (n=26) admitted to the ICU, 13.9% (n=14) requiring MRA, and 5% (n=5) resulting in death. The presence of thrombocytopenia (OR=13.3, 95% CI 2-80), abnormalities in chest X-rays (OR=33.5, 95% CI 5-225), and absence of headache (OR=6.8, 95% CI 1-32) were predictors of PCO. Conclusions: Consistent with the literature, pulmonary involvement and thrombocytopenia are independent risk factors for poor clinical outcomes. In our series, the pre-sence of headache was a protective symptom

Comprehensive evaluation of the effectiveness of endemic disease prevention and control in Jiangsu Province, China, 2013-2022.

As a strong economic and populous province in China, Jiangsu is home to four endemic diseases. Despite efforts in the past decade, the prevention and control of these four endemic diseases are not uniform because of the different etiological chains and influencing factors of these diseases. Among the evaluation methodologies for endemic disease control, only one method is currently available for each disease. In this study, we selected 14 indicators to comprehensively evaluate the effectiveness of endemic disease control in Jiangsu between 2013 and 2022. We improved the method for calculating the weights of the indicators and established a fuzzy comprehensive evaluation model based on the weighted Technique for Order Preference by Similarity to an Ideal Solution model and a weighted grey relational analysis model. The results of the comprehensive evaluation showed that the progress of endemic disease control in Jiangsu was not always in line with our expectations of improvement, with the top five years of better control occurring in 2015, 2013, 2021, 2022, and 2014. The results of the sensitivity analysis confirm the reliability and accuracy of these findings. We discovered that measures such as the reform of the salt industry, use of thyroid ultrasound, and new water supply projects for residents in Jiangsu affected the progress of endemic disease prevention and control. The tracking of endemic disease status should consider the potential effects of changes in policies implemented in other industries on endemic disease prevention and control. Additionally, the results of this study provide a theoretical basis for enhancing prevention and control practices in other regions of China.

A participatory approach to understand the attitudes and perceptions towards priority endemic cattle diseases among dairy farmers and animal health experts in Henan province, China.

The dairy industry is threatened by a variety of endemic diseases and emerging diseases, and various control programs have been initiated in China. The increased application of evidence to policymaking can help improve the efficiency of disease control programs; however, the relevant research literature is currently lacking. The objective of this study was to gain an in-depth understanding of the attitudes and perceptions towards priority endemic diseases among dairy farmers and animal health experts by taking Henan province of China as the example and using semi-structured interviews and focus group discussions, respectively. This study involved 24 farmers and 27 animal health experts from December 2019 to January 2021. The diseases considered by farmers to be of significance to their animals are different from those considered priorities by the participating experts and the government list. From the perspective of the individual farmers, the effects of zoonotic disease risks such as bovine brucellosis and tuberculosis appear to be less pronounced than "visible" losses at the farm level, contrary to the opinion of experts. Participating experts believed that poor on-farm biosecurity measures posed challenges to the control and eradication of priority endemic diseases; however, there are gaps in farmers' understanding of biosecurity principles, and low motivations to take such disease prevention measures. Several other challenges to the control and eradication of priority endemic diseases also emerged in the data, including the lack of diagnostic tools applicable in the field as well as differential diagnostic tools to differentiate natural infection from vaccination, lack of effective and commercially available vaccines against single or multiple pathogen(s) or new genotypes/serotypes, weak early warning and information networks and insufficient economic compensation. A holistic understanding of people's perceptions of disease control would facilitate the implementation of inclusive and engaging disease control strategies, thereby increasing the efficiency of disease control.

[Progress of schistosomiasis control in People's Republic of China in 2022].

This report presented the endemic status of schistosomiasis and analyzed the data collected from the national schistosomiasis prevention and control system and national schistosomiasis surveillance program in the People's Republic of China in 2022. Among the 12 provinces (municipality and autonomous region) endemic for schistosomiasis, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to maintain the achievements of schistosomiasis elimination, and Sichuan and Jiangsu provinces maintained the criteria of transmission interruption, while Yunnan, Hubei, Anhui, Jiangxi and Hunan provinces maintained the criteria of transmission control by the end of 2022. A total of 452 counties (cites, districts) were found to be endemic for schistosomiasis in China in 2022, with 27 434 endemic villages covering 73 424 400 people at risk of infections. Among the 452 endemic counties (cities, districts), 75.89% (343/452), 23.45% (106/452) and 0.66% (3/452) achieved the criteria of elimination, transmission interruption and transmission control of schistosomiasis, respectively. In 2022, 4 317 356 individuals received serological tests for schistosomiasis, and 62 228 were sero-positive. A total of 208 646 individuals received stool examinations for schistosomiasis, with one positive and another two cases positive for urine microscopy, and these three 3 cases were imported schistosomiasis patients from Africa. There were 28 565 cases with advanced schistosomiasis documented in China by the end of 2022. Oncomelania hupensis snail survey was performed in 18 891 endemic villages in China in 2022 and O. hupensis snails were found in 6 917 villages (36.62% of all surveyed villages), with 8 villages identified with emerging snail habitats. Snail survey was performed at an area of 655 703.01 hm2 and 183 888.60 hm2 snail habitats were found, including 110.58 hm2 emerging snail habitats and 844.35 hm2 re-emerging snail habitats. There were 477 200 bovines raised in the schistosomiasis endemic areas of China in 2022, and 113 946 bovines received serological examinations for schistosomiasis, with 204 sero-positives detected. Among the 131 715 bovines received stool examinations, no positives were identified. In 2022, there were 19 726 schistosomiasis patients receiving praziquantel chemotherapy, and expanded chemotherapy was performed in 714 465 person-time for humans and 234 737 herd-time for bovines in China. In 2022, snail control with chemical treatment was performed at an area of 119 134.07 hm2, and the actual area of chemical treatment was 65 825.27 hm2, while environmental improvements were performed at an area of 1 163.96 hm2. Data from the national schistosomiasis surveillance program of China showed that the mean prevalence of Schistosoma japonicum infections was both zero in humans and bovines in 2022, and no S. japonicum infection was detected in O. hupensis snails. These data demonstrated that the endemic status of schistosomiasis continued to decline in China in 2022, with 3 confirmed schistosomiasis patients that had a foreign nationality and all imported from Africa, and the areas of snail habitats remained high. Further improvements in the construction of the schistosomaisis surveillance and forecast system, and reinforcement of O. hupensis survey and control are required to prevent the re-emerging schistosomiasis.

The right strategy for you: Using the preferences of beef farmers to guide biosecurity recommendations for on-farm management of endemic disease.

Effective on-farm biosecurity measures are crucial to the post-border protection of emerging agricultural diseases and are the foundation of endemic disease control. Implementation of on-farm biosecurity measures are contingent on the priorities of individual producers, which can often be neglected for other aspects of the farming enterprise. The on-farm approach to prevention of endemic diseases, like bovine viral diarrhoea virus (BVDV), is inconsistent between farms and it is not realistic to assume that farmers take an entirely normative approach to on-farm decision making. Multi-criteria decision analysis (MCDA) has been used for disease prioritisation and national disease control in human and animal health; however, it is yet to be used as a decision tool for disease control at the farm level. This study used MCDA to determine the most appropriate biosecurity combinations for management of BVDV, based on the preferences of Australian beef producers. Beef producer preferences were obtained from an online survey using indirect collection methods. Point of truth calibration was used to aggregate producer preferences and the performance scores of 23 biosecurity combinations for control of BVDV based on four main criteria: the probability of BVDV introduction, the on-farm impact of BVDV, the off-farm impact of BVDV and the annual input cost of the practice. The MCDA found that biosecurity combinations that included "double-fencing farm boundaries" used in conjunction with "vaccination against BVDV" were most appropriate for management of BVDV in an initially naïve, self-replacing seasonal single-calving beef herd over a 15-year period. Beef producers prioritised practices that preserved the on-farm health of their cattle more than any other criteria, a finding that was persistent regardless of demographic or farming type. Consequently, combinations with "vaccination against BVDV" were consistently ranked higher than those that included "strategic exposure of a persistently infected cow," which is sometimes used by Australian beef producers instead of vaccination. Findings of this study indicate that the benefits of "double-fencing farm boundaries" and "vaccination against BVDV" outweigh the relatively high cost associated with these practices based on the priorities of the Australian beef producer and may be used to demonstrate the benefits of on-farm biosecurity during discussions between livestock veterinarians and beef farmers.

Ámbito biológico, social, tecnológico, económico, normativo y político del plan hacia la eliminación de la malaria en el Perú 2022-2030 / Biological, social, technological, economic, regulatory and political scope of the plan towards the elimination of malaria in Peru 2022-2030

La malaria es producida por parásitos del género Plasmodium y transmitida por Anopheles. Es considerada un problema de salud pública; a pesar de la reducción significativa de los casos, a nivel mundial, persisten tasas de morbi-mortalidad elevadas. En las Américas, recientemente, se registró brotes palúdicos importantes en seis países, el Perú fue uno de ellos, generando la iniciativa para crear el Plan hacia la Eliminación de la Malaria en el Perú (PEMP), partiendo de la experiencia en el Departamento de Loreto en marco del Plan Malaria Cero. El PEMP, tiene la finalidad de reducir el 90% los casos de malaria antes de 2030, con un enfoque comunitario. El objetivo de este estudio fue evaluar la integralidad del PEMP referidas a los ámbitos biológico, social, tecnológico, económico, normativo y político. Se conformó un grupo de expertos, quienes realizaron la validez aparente de cada uno de los conceptos (DDP< 2,4). Posteriormente, la congruencia de causas por ámbitos y, la contribución por objetivos específicos dentro de cada ámbito. Encontrándose coherencias entre los objetivos específicos, planes y/o acciones dentro de cada ámbito. Se corroboró el enfoque integral del PEMP, encaminando en trabajo multidisciplinario y de comprensión integral de los desafíos actuales para la eliminación de la malaria. Se identifica como debilidad la falta de abordaje de los reservorios de malaria; se recomienda realizar búsqueda activa de casos e investigaciones en hospedadores no humano, especialmente en zonas de alta transmisión; e implementarse un diseño de enfoque holístico como parte del abordaje integral(AU)

Malaria is produced by parasites of the genus Plasmodium and transmitted by Anopheles. It is considered a public health problem; Despite the significant reduction in cases, worldwide, high morbidity and mortality rates persist. In the Americas, important malaria outbreaks were recently registered in six countries, Peru was one of them, generating the initiative to create the Plan for the Elimination of Malaria in Peru (PEMP), based on the experience in the Department of Loreto within the framework of the Zero Malaria Plan. The PEMP aims to reduce malaria cases by 90% before 2030, with a community approach. The objective of this study was to evaluate the integrality of the PEMP referring to the biological, social, technological, economic, regulatory and political fields. A group of experts was formed, who carried out the apparent validity of each one of the concepts (DDP < 2.4). Subsequently, the congruence of causes by areas and the contribution by specific objectives within each area. Finding coherence between the specific objectives, plans and/or actions within each area. The integral approach of the PEMP was confirmed, leading to multidisciplinary work and a comprehensive understanding of the current challenges for the elimination of malaria. The lack of approach to malaria reservoirs is identified as a weakness; It is recommended to carry out active search for cases and investigations in non-human hosts, especially in areas of high transmission; and a holistic approach design implemented as part of the comprehensive approach(AU)

Combining epidemiology and economics to assess control of a viral endemic animal disease: Porcine Reproductive and Respiratory Syndrome (PRRS).

Porcine reproductive and respiratory syndrome (PRRS) is an extremely contagious disease that causes great damage to the U.S. pork industry. PRRS is not subject to official control in the U.S., but most producers adopt control strategies, including vaccination. However, the PRRS virus mutates frequently, facilitating its ability to infect even vaccinated animals. In this paper we analyze how increased vaccination on sow farms reduces PRRS losses and when vaccination is profitable. We develop a SIR model to simulate the spread of an outbreak between and within swine farms located in a region of Minnesota. Then, we estimate economic losses due to PRRS and calculate the benefits of vaccination. We find that increased vaccination of sow farms increases the private profitability of vaccination, and also transmits positive externalities to farms that do not vaccinate. Although vaccination reduces industry losses, a low to moderate vaccine efficacy implies that large PRRS losses remain, even on vaccinated farms. Our approach provides useful insight into the dynamics of an endemic animal disease and the benefits of different vaccination regimens.

Knowledge, attitudes, and practices regarding schistosomiasis infection and prevention: A mixed-methods study among endemic communities of western Uganda.

INTRODUCTION: In Uganda, schistosomiasis (re)infections have continued to remain high despite the implementation of mass drug administration and sensitization campaigns aimed at controlling the disease. This could imply that there are some barriers to the implemented preventive measures. We conducted a mixed-methods study in Kagadi and Ntoroko districts around Lake Albert to assess knowledge, attitudes, and practices regarding schistosomiasis and to explore and understand perspectives regarding the disease. MATERIALS AND METHODS: Semi-structured survey questionnaires were administered to 337 household adults selected through systematic random sampling. We also interviewed 12 participants and held 28 focus-group discussion sessions with 251 individuals respectively. Quantitative data was analysed using frequencies, percentages, and chi-square tests for associations, while themes and sub-themes were used to analyse qualitative data respectively. FINDINGS: A total of 98.5%, 81.3%, and 78.5% had heard about schistosomiasis, and knew the main transmission modes and symptoms, respectively. The majority (75.8%) said avoiding contact with water was a preventative way, while 67.5% said observing signs and symptoms was a form of diagnosis. Furthermore, 98.4% and 73.4% said it was important to defecate in latrines and to avoid contact with contaminated water respectively. However, it is difficult to avoid contact with lake water because it is the only source of livelihood, especially for fisher communities. Open defecation is commonly practiced along the lake due to insufficient space and difficulties in the construction of latrines. Myths and misconceptions reported include; lake water is safe, gassing in water causes transmission, fetching water early in the morning and from deep water is safe, and feces in the lake water act as a bait for catching fish. CONCLUSIONS AND RECOMMENDATIONS: Despite adequate knowledge of schistosomiasis and a positive attitude towards its prevention, existing myths and misconceptions, coupled with persistent risky water, sanitation, and hygiene practices still pose a challenge. A more robust community-based awareness intervention using bottom-up participatory approaches, accompanied by the provision of clean and safe water sources and increasing latrine coverage, could provide lasting solutions to these barriers.

The cost of tsetse control using 'Tiny Targets' in the sleeping sickness endemic forest area of Bonon in Côte d'Ivoire: Implications for comparing costs across different settings.

BACKGROUND: Work to control the gambiense form of human African trypanosomiasis (gHAT), or sleeping sickness, is now directed towards ending transmission of the parasite by 2030. In order to supplement gHAT case-finding and treatment, since 2011 tsetse control has been implemented using Tiny Targets in a number of gHAT foci. As this intervention is extended to new foci, it is vital to understand the costs involved. Costs have already been analysed for the foci of Arua in Uganda and Mandoul in Chad. This paper examines the costs of controlling Glossina palpalis palpalis in the focus of Bonon in Côte d'Ivoire from 2016 to 2017. METHODOLOGY/PRINCIPAL FINDINGS: Some 2000 targets were placed throughout the main gHAT transmission area of 130 km2 at a density of 14.9 per km2. The average annual cost was USD 0.5 per person protected, USD 31.6 per target deployed of which 12% was the cost of the target itself, or USD 471.2 per km2 protected. Broken down by activity, 54% was for deployment and maintenance of targets, 34% for tsetse surveys/monitoring and 12% for sensitising populations. CONCLUSIONS/SIGNIFICANCE: The cost of tsetse control per km2 of the gHAT focus protected in Bonon was more expensive than in Chad or Uganda, while the cost per km2 treated, that is the area where the targets were actually deployed, was cheaper. Per person protected, the Bonon cost fell between the two, with Uganda cheaper and Chad more expensive. In Bonon, targets were deployed throughout the protected area, because G. p. palpalis was present everywhere, whereas in Chad and Uganda G. fuscipes fuscipes was found only the riverine fringing vegetation. Thus, differences between gHAT foci, in terms of tsetse ecology and human geography, impact on the cost-effectiveness of tsetse control. It also demonstrates the need to take into account both the area treated and protected alongside other impact indicators, such as the cost per person protected.

Measles.

Measles is a highly contagious, potentially fatal, but vaccine-preventable disease caused by measles virus. Symptoms include fever, maculopapular rash, and at least one of cough, coryza, or conjunctivitis, although vaccinated individuals can have milder or even no symptoms. Laboratory diagnosis relies largely on the detection of specific IgM antibodies in serum, dried blood spots, or oral fluid, or the detection of viral RNA in throat or nasopharyngeal swabs, urine, or oral fluid. Complications can affect many organs and often include otitis media, laryngotracheobronchitis, pneumonia, stomatitis, and diarrhoea. Neurological complications are uncommon but serious, and can occur during or soon after the acute disease (eg, acute disseminated encephalomyelitis) or months or even years later (eg, measles inclusion body encephalitis and subacute sclerosing panencephalitis). Patient management mainly involves supportive therapy, such as vitamin A supplementation, monitoring for and treatment of secondary bacterial infections with antibiotics, and rehydration in the case of severe diarrhoea. There is no specific antiviral therapy for the treatment of measles, and disease control largely depends on prevention. However, despite the availability of a safe and effective vaccine, measles is still endemic in many countries and causes considerable morbidity and mortality, especially among children in resource-poor settings. The low case numbers reported in 2020, after a worldwide resurgence of measles between 2017 and 2019, have to be interpreted cautiously, owing to the effect of the COVID-19 pandemic on disease surveillance. Disrupted vaccination activities during the pandemic increase the potential for another resurgence of measles in the near future, and effective, timely catch-up vaccination campaigns, strong commitment and leadership, and sufficient resources will be required to mitigate this threat.

HIV/AIDS-Pneumonia Codynamics Model Analysis with Vaccination and Treatment.

In this paper, we proposed and analyzed a realistic compartmental mathematical model on the spread and control of HIV/AIDS-pneumonia coepidemic incorporating pneumonia vaccination and treatment for both infections at each infection stage in a population. The model exhibits six equilibriums: HIV/AIDS only disease-free, pneumonia only disease-free, HIV/AIDS-pneumonia coepidemic disease-free, HIV/AIDS only endemic, pneumonia only endemic, and HIV/AIDS-pneumonia coepidemic endemic equilibriums. The HIV/AIDS only submodel has a globally asymptotically stable disease-free equilibrium if ℛ 1 < 1. Using center manifold theory, we have verified that both the pneumonia only submodel and the HIV/AIDS-pneumonia coepidemic model undergo backward bifurcations whenever ℛ 2 < 1 and ℛ 3 = max{ℛ 1, ℛ 2} < 1, respectively. Thus, for pneumonia infection and HIV/AIDS-pneumonia coinfection, the requirement of the basic reproduction numbers to be less than one, even though necessary, may not be sufficient to completely eliminate the disease. Our sensitivity analysis results demonstrate that the pneumonia disease transmission rate ß 2 and the HIV/AIDS transmission rate ß 1 play an important role to change the qualitative dynamics of HIV/AIDS and pneumonia coinfection. The pneumonia infection transmission rate ß 2 gives rises to the possibility of backward bifurcation for HIV/AIDS and pneumonia coinfection if ℛ 3 = max{ℛ 1, ℛ 2} < 1, and hence, the existence of multiple endemic equilibria some of which are stable and others are unstable. Using standard data from different literatures, our results show that the complete HIV/AIDS and pneumonia coinfection model reproduction number is ℛ 3 = max{ℛ 1, ℛ 2} = max{1.386, 9.69 } = 9.69 at ß 1 = 2 and ß 2 = 0.2 which shows that the disease spreads throughout the community. Finally, our numerical simulations show that pneumonia vaccination and treatment against disease have the effect of decreasing pneumonia and coepidemic disease expansion and reducing the progression rate of HIV infection to the AIDS stage.

Oral manifestations of systemic fungal infections: 25-year experience in an endemic region

Some mycoses are endemic. They develop through hematogenous spread, causing a generalized infection, usually with secondary mucosal involvement.The aim of this observational and retrospective study was to report the prevalence and characteristics of oral lesions in patients diagnosed with systemic fungal infections (SFI) over a 25-year period in southern Brazil. Demographic (age, sex, ethnicity, occupation) and clinical (anatomical location, symptoms,histopathological diagnosis and management) data from the medical records of patients with SFI were collected from 1995 to 2019. 34 cases of SFI were found, of which 31 (91.18%) were diagnosed as paracoccidioidomycosis (PCM) and 3 (8.82%) as histoplasmosis. Men were much more affected (n = 31; 91.18%), with an average age of 46.9 years. Most patients (n = 18; 58.06%) were Caucasian; 48% (n = 15) were farm/rural workers and the most affected region was the jugal mucosa (n = 13; 25.49%) followed by the alveolar ridge (n = 12; 23.52%). All patients with histoplasmosis were immunocompetent men (mean age: 52.67 years), and the palate was the most affected. All patients underwent incisional biopsy and were referred to an infectologist. The dentist has an essential role in the recognition of SFI, whose oral manifestations may be the first sign. SFI should be included in differential diagnosis in patients from endemic areas. In addition, the inevitable human mobility and globalization make knowledge of these mycosesnecessary worldwide, especially since advanced cases in immunocompromised patients can be fatal.

Loiasis is endemic in the Ndikinimeki Health District (Centre Region, Cameroon) but does not represent a hindrance to onchocerciasis elimination.

Community-Directed Treatment with Ivermectin (CDTI) is the strategy of choice to fight onchocerciasis in Africa. In areas where loiasis is endemic, onchocerciasis control and/or elimination is hindered by severe adverse events (SAEs) occurring after ivermectin mass treatments. This study aimed at (i) investigating the impact of two decades of CDTI on L. loa clinical and parasitological indicators in the Ndikinimeki Health District, and (ii) assessing the risk of SAEs after this long-term preventive chemotherapy. A cluster-based cross-sectional survey was conducted in the six Health Areas of the Ndikinimeki Health District. All volunteers underwent day-time calibrated thick blood smears to search for L. loa microfilariae, as well as an interview to assess the history of migration of eye worm and Calabar swelling. The overall prevalence of L. loa microfilaraemia was 2.2 % (95% CI: 1.3-3.7%), and the proportions of individuals who had already experienced eye worm and/or Calabar swelling were 1.0% and 0.5%, respectively. The mean microfilarial density was 63.55 (SD: 559.17; maximum: 9220.0) mf/mL. These findings indicate that (i) the long-term ivermectin-based preventive chemotherapy against onchocerciasis significantly reduced L. loa clinical and parasitological indicators, and (ii) the risk of developing neurologic and potentially fatal SAE after ivermectin mass treatment is zero in the Ndikinimeki Health District.

A comprehensive review on endemic and experimental fluorosis in sheep: Its diverse effects and prevention.

Fluoride is a natural element widely distributed in the environment and plays an important role in the growth of humans and animals. However, in many species, high concentrations of fluoride induce several problems, such as dental, skeletal, and non-skeletal fluorosis. Sheep living in endemic areas are sensitive to the chronic toxicity of fluoride, and they have been found to suffer not only from teeth and bone problems but also from other organs. Studies indicating the chronic harmful effects of fluoride on teeth, bones, blood biochemical parameters, kidney, liver, heart, reproductive system and growth in sheep have been clearly summarized in this review. Besides, this work also includes updated progress in terms of prevention or reduction of fluoride toxicity in this species.

Planejamento, síntese e avaliação biológica de candidatos a fármacos: busca de inibidores epigenéticos da Sirtuína 2 Sir2 / Design, synthesis and biological evaluation of drug candidates: search for Sirtuin 2 (Sir 2) epigenetic inhibitors

As doenças negligenciadas são causadas por agentes infecciosos e parasitários, como vírus, bactérias, protozoários e helmintos. Essas doenças são prevalentes em populações de baixa renda que vivem em países em desenvolvimento e são responsáveis por incapacitar e levar milhares de pessoas à morte. Este nome se dá pois, apesar de sua grande relevância médica, recebem pouca atenção dos governos e indústrias farmacêuticas. Dentre essas doenças podemos destacar a Doença de Chagas, doença infecciosa causada pelo parasita hemoflagelado Trypanosoma cruzi. Endêmica em 21 países, com 6 a 7 milhões de pessoas infectadas resultando em 7500 mortes por ano. A quimioterapia disponível contra essa parasitose é baseada em apenas dois medicamentos, o benznidazol e o nifurtimox, ativos principalmente na fase aguda da doença e com efeitos adversos graves que comprometem a adesão ao tratamento e, além disso, apesar dos enormes esforços na pesquisa de novos agentes antichagásicos em nível nacional e internacional, na maioria realizada academicamente, ainda não foram encontradas alternativas terapêuticas para a doença, persistindo, assim, a necessidade de descoberta e desenvolvimento de novos fármacos. O início de um planejamento de um novo fármaco se dá pela definição de um alvo bioquímico a ser utilizado na busca de moléculas que possam exercer a função de inibidores ou moduladores, conforme a atividade biológica desejada. Neste sentido, as sirtuínas 2 (Sir2) são enzimas que se mostraram essenciais para o crescimento in vitro do T. cruzi em suas formas amastigota e epimastigota. No caso de tripanossomatídeos, em geral, a superexpressão de Sir2 está relacionada à sobrevivência de formas amastigotas. Assim, essas evidências indicam que a Sir2 de tripanosomatídeos tem grande potencial como alvo biológico na busca e desenvolvimento de novos fármacos antichagásicos. O objetivo principal deste projeto foi identificar moléculas que apresentaram atividade inibitória para a sirtuína 2 de T. cruzi por meio da utilização da estratégia de Planejamento de Fármacos Baseada no Ligante - Ligand Based Drug Design (LBDD) e o desenvolvimento de análogos dos inibidores da Sir2. A modificação molecular está entre algumas das técnicas tradicionais usadas no desenvolvimento racional de um fármaco, e é usada principalmente no desenvolvimento de análogos, e busca melhorar as propriedades farmacocinéticas e/ou farmacodinâmicas de um protótipo, obter propriedades de interação semelhantes ao alvo e, em alguns casos, revelar uma atividade biológica. Com este intuito, análogos do sirtinol e da salermida foram sintetizados e uma nova rota sintética utilizando o microrreator em fluxo contínuo foi desenvolvida e apresentou rendimento superior quando comparado à síntese em bancada. A partir desta metodologia foram obtidos 20 compostos. Os ensaios in vitro contra formas amastigotas do T. cruzi indicaram que 8 compostos inibiram a atividade parasitária em mais de 50%, na dose de 10 µM, sendo que alguns destes apresentaram maior inibição parasitária quando comparados ao benznidazol, o fármaco de referência e único disponível no Brasil. Com estes resultados preliminares, novos ensaios estão sendo realizados para identificar potência e mecanismo de ação destes candidatos a agentes tripanomicidas

Neglected diseases are caused by infectious and parasitic agents such as viruses, bacteria, protozoa and helminths. These diseases are prevalent in low-income populations living in developing countries and are responsible for disabling and killing thousands of people. They get this name because, despite their great medical relevance, they end up receiving little attention from governments and pharmaceutical industries. Among these diseases, we can highlight Chagas disease, an infectious endemic disease caused by the hemoflagellate parasite Trypanosoma cruzi. This disease is endemic in 21 countries, with 6 to 7 million people infected resulting in 7,500 deaths per year. Chemotherapy is based on just two drugs, benznidazole and nifurtimox, which are mainly active in the acute phase of the disease. These drugs have adverse effects that compromise adherence, even more, considering that they are not effective from the point of view of the chronic phase of the disease. Despite the enormous efforts in researching new anti-chagasic agents at the national and international level, and mostly carried out academically, therapeutic alternatives for the disease have not yet been found, thus, the need for the discovery and development of new drugs persists. Sirtuins 2 (Sir2) are enzymes that have been shown to be essential for the in vitro growth of T. cruzi in its amastigote and epimastigote forms. In the case of trypanosomatids in general, Sir2 overexpression is related to the survival of amastigote forms. Sir2 inhibitors, such as sirtinol, have shown efficacy in leishmanicides. Thus, these evidences indicate that Sir2 from trypanosomatids can be considered as a biological target in the search and development of new anti-chagasic drugs. The beginning of a new drug planning study is the definition of a biochemical target to be used in the search for molecules that can play the role of inhibitors or modulators, according to the desired biological activity. The main objective of this project was to identify molecules that presented inhibitory activity to sirtuin 2 of T. cruzi using the Ligand Based Drug Design (LBDD) strategy of planning and the development of analogues of Sir2 inhibitors. Molecular modification is a traditional technique used in the rational development of a drug, as well as the use of natural products, combinatorial chemistry, high-throughput screening (HTS), among others. Mainly used in the development of analogues, molecular modification is applied for different purposes, among them, it seeks to improve the pharmacokinetic and/or pharmacodynamic properties of a prototype, obtain target-like interaction properties and, in some cases, reveal an activity biological. For this purpose, analogues of sirtinol and salermide were synthesized and a new synthetic route using the microreactor in continuous flow was developed and presented superior yield when compared to benchtop synthesis. From this methodology, 20 compounds were obtained. in vitro assays against amastigote forms of T. cruzi indicated that 8 compounds inhibited parasitic activity by more than 50% at a dose of 10 µM, and some of these showed greater parasitic inhibition when compared to benznidazole, the reference drug, and only available in Brazil. With these preliminary results, new assays are being carried out to identify the potency and mechanism of action of these candidate trypanocidal agents