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

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)

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.

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

Hacia un mundo libre de malaria: Utopía o realidad / Towards a malaria-free world: Utopia or reality

La Malaria es una enfermedad causada por un parásito que se transmite a los humanos a través de la picadura de mosquito hembra Anophele. Reportando la WHO en el 2019, 229 millones de casos y 409.000 muertes por la enfermedad en 87 paises del mundo, Existen seis especies de este párasito: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale wallickeri, Plasmodium ovale curtisi, Plasmodium malariae y Plasmodium knowlesi. Siendo la especie P. falciparum la causante de mayor morbilidad, con tasa entre 10 y 50% de mortalidad por malaria complicada. Alrededor de 108 países han declarado la malaria como enfermedad endémica, pudiendo padecer la enfermedad en cualquier época del año. Sin embargo, en el caso de América Latina hoy en día se vive un estancamiento de la enfermedad, reportándose en países menos de 100 casos autóctonos entre el 2000 y 2019, con algunas excepciones. Esta situación de vulnerabilidad de países como Brasil, Colombia, la frontera Perú-Ecuador, Venezuela, se incrementan ante la presencia activa de la pandemia producto del Covid -19 aunado a restricciones económicas, incremento de la actividad minera, o políticas públicas que ponen en riesgo la sostenibilidad del programa de control de la enfermedad. Para el 2021 la OMS corrobora que existen 87 países con malaria a nivel mundial, de los cuales 24 de ellos habían interrumpido su transmisión autóctona por 3 años. Realidad que consolidad la propuesta tras la experiencia adquirida, que cualquiera que sea la situación epidemiológica de entrada, el trabajo hacia la erradicación de la malaria debe entenderse y atenderse como un proceso continuo donde los propios Estados deben desde su realidad y estrategias propias se articulen con el Plan Estratégico Técnico Mundial Contra la Malaria 2016-2030 propuesto por la OMS(AU)

Malaria is a disease caused by a parasite that is transmitted to humans through the bite of the female Anophele mosquito. Reporting the WHO in 2019, 229 million cases and 409,000 deaths from the disease in 87 countries of the world, There are six species of this parasite: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale wallickeri, Plasmodium ovale curtisi, Plasmodium malariae and Plasmodium knowlesi. The species P. falciparum is the cause of greatest morbidity, with a rate between 10 and 50% of mortality from complicated malaria. About 108 countries have declared malaria as an endemic disease, and the disease can occur at any time of the year. However, in the case of Latin America today there is a stagnation of the disease, with fewer than 100 indigenous cases reported in countries between 2000 and 2019, with some exceptions. This situation of vulnerability of countries such as Brazil, Colombia, the Peru-Ecuador border, Venezuela, increases in the face of the active presence of the pandemic product of the Covid -19 coupled with economic restrictions, increased mining activity, or public policies that put at risk the sustainability of the disease control programme. By 2021, WHO confirms that there are 87 countries with malaria worldwide, of which 24 had interrupted their indigenous transmission for 3 years. Reality that consolidates the proposal after the experience acquired, that whatever the epidemiological situation of entry, The work towards the eradication of malaria must be understood and addressed as a continuous process where the States themselves must from their own reality and strategies articulate with the Global Technical Strategic Plan Against Malaria 2016-2030 proposed by the WHO(AU)

Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings.

Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of this debilitating disease. As some promising schistosomiasis vaccine candidates are moving through pre-clinical and clinical testing, we review the immunological challenges that these vaccine candidates may encounter in transitioning through the clinical trial phases in endemic settings. Prior exposure of the target population to schistosomes and other infections may impact vaccine response and efficacy and therefore requires considerable attention. Schistosomes are known for their potential to induce T-reg/IL-10 mediated immune suppression in populations which are chronically infected. Moreover, endemicity of schistosomiasis is focal whereby target and trial populations may exhibit several degrees of prior exposure as well as in utero exposure which may increase heterogeneity of vaccine responses. The age dependent distribution of exposure and development of acquired immunity, and general differences in the baseline immunological profile, adds to the complexity of selecting suitable trial populations. Similarly, prior or concurrent infections with other parasitic helminths, viral and bacterial infections, may alter immunological responses. Consequently, treatment of co-infections may benefit the immunogenicity of vaccines and may be considered despite logistical challenges. On the other hand, viral infections leave a life-long immunological imprint on the human host. Screening for serostatus may be needed to facilitate interpretation of vaccine responses. Co-delivery of schistosome vaccines with PZQ is attractive from a perspective of implementation but may complicate the immunogenicity of schistosomiasis vaccines. Several studies have reported PZQ treatment to induce both transient and long-term immuno-modulatory effects as a result of tegument destruction, worm killing and subsequent exposure of worm antigens to the host immune system. These in turn may augment or antagonize vaccine immunogenicity. Understanding the complex immunological interactions between vaccine, co-infections or prior exposure is essential in early stages of clinical development to facilitate phase 3 clinical trial design and implementation policies. Besides well-designed studies in different target populations using schistosome candidate vaccines or other vaccines as models, controlled human infections could also help identify markers of immune protection in populations with different disease and immunological backgrounds.

Detection of dengue, chikungunya, and Zika RNA in blood donors from Southeast Asia.

BACKGROUND: Chikungunya (CHIKV), dengue (DENV), and Zika (ZIKV) viruses are of concern due to the potential of transfusion transmission in blood, especially in regions such as Southeast Asia where the viruses are endemic. The recent availability of nucleic acid testing (NAT) to screen blood donations on an automated platform provides the opportunity to detect potentially infectious units in asymptomatic donors. STUDY DESIGN AND METHODS: Three thousand blood donations from Vietnam and 6000 from Thailand were screened with a real-time polymerase chain reaction (PCR) test (cobas CHIKV/DENV, Roche Diagnostics, Indianapolis, IN) and equal numbers on cobas Zika (Roche Diagnostics). Reactive samples were tested by alternative NAT with resolution of discordant results by heminested PCR. Throughput of simultaneous testing of the two assays on the cobas 8800 system (Roche Diagnostics) was evaluated. RESULTS: In Vietnam, 9 of 3045 samples were reactive for DENV and all were confirmed, for a prevalence (with 95% confidence interval [CI]) of 0.296% (0.135-0.560). In Thailand, 2 of 6000 samples were reactive for CHIKV, 4 of 6000 for DENV, and 1 of 6005 for ZIKV, and all confirmed. The prevalence of CHIKV is 0.033% (0.004-0.120), DENV 0.067% (0.018-0.171), and ZIKV 0.017% (0.000-0.093). The overall specificity for the cobas CHIKV/DENV and cobas Zika tests was 100% (99.959-100). For the simultaneous assay testing, 960 test results were available in 7 hours and 53 minutes. CONCLUSION: Detection of CHIKV, DENV, and ZIKV RNA in donor samples in Vietnam and Thailand indicate the presence of the virus in asymptomatic blood donors. The cobas 6800/8800 systems (Roche Molecular Systems, Pleasanton, CA) enable screening blood donations in endemic areas for these viruses together or separately.

A Model of Care Optimized for Marginalized Remote Population Unravels Migration Pattern in India.

BACKGROUND AND AIMS: Access to basic health needs remains a challenge for most of world's population. In this study, we developed a care model for preventive and disease-specific health care for an extremely remote and marginalized population in Arunachal Pradesh, the northeasternmost state of India. APPROACH AND RESULTS: We performed patient screenings, performed interviews, and obtained blood samples in remote villages of Arunachal Pradesh through a tablet-based data collection application, which was later synced to a cloud database for storage. Positive cases of hepatitis B virus (HBV) were confirmed and genotyped in our central laboratory. The blood tests performed included liver function tests, HBV serologies, and HBV genotyping. HBV vaccination was provided as appropriate. A total of 11,818 participants were interviewed, 11,572 samples collected, and 5,176 participants vaccinated from the 5 westernmost districts in Arunachal Pradesh. The overall hepatitis B surface antigen (HBsAg) prevalence was found to be 3.6% (n = 419). In total, 34.6% were hepatitis B e antigen positive (n = 145) and 25.5% had HBV DNA levels greater than 20,000 IU/mL (n = 107). Genotypic analysis showed that many patients were infected with HBV C/D recombinants. Certain tribes showed high seroprevalence, with rates of 9.8% and 6.3% in the Miji and Nishi tribes, respectively. The prevalence of HBsAg in individuals who reported medical injections was 3.5%, lower than the overall prevalence of HBV. CONCLUSIONS: Our unique, simplistic model of care was able to link a highly resource-limited population to screening, preventive vaccination, follow-up therapeutic care, and molecular epidemiology to define the migratory nature of the population and disease using an electronic platform. This model of care can be applied to other similar settings globally.

The Botfly, A Tropical Menace: A Distinctive Myiasis Caused by Dermatobia hominis.

Dermatobia hominis, also known as the human botfly, is native to tropical and subtropical Central and South America and seen in travelers from endemic to temperate regions including the United States and Europe. Cutaneous infestation botfly myiasis involves the development of D. hominis larvae in the skin and is common in tropical locations. The distinct appearance of a cutaneous D. hominis infestation facilitates early diagnosis and intervention where cases are common. However, the identification of D. hominis in temperate regions may prove challenging due to its rarity. D. hominis may be misdiagnosed as folliculitis, an epidermal cyst, or an embedded foreign object with secondary impetigo. One should have a heightened suspicion in someone returning from a vacation in an endemic area, such as Belize. Here we describe the presentation, differential diagnosis, and treatment and encourage enhanced preventative measures among tourists when visiting tropical and subtropical regions. Additionally, we propose a novel classification system for assessing the various stages of infestation and suggest that patients reporting travel to Latin America and experiencing pain disproportionate to an insect bite should lead physicians to consider myiasis caused by D. hominis.

Integração do agente de combate às endemias na Estratégia Saúde da Família, Campo Grande, Mato Grosso do Sul, 2017* / Integración del agente de combate a las endemias en la Estrategia Salud Familiar, Campo Grande, Mato Grosso do Sul, Brasil, 2017 / Integration of endemic disease control workers in the Family Health Strategy, Campo Grande, Mato Grosso do Sul, Brazil, 2017

Objetivo: Descrever o processo de integração do agente de combate às endemias (ACE) na Estratégia Saúde da Família (ESF). Métodos: Estudo transversal descritivo. Os dados foram coletados por questionário semiestruturado autoaplicável, de fevereiro a maio de 2017, em quatro unidades de Saúde da Família na região urbana de Campo Grande, Mato Grosso do Sul, Brasil. Resultados: Participaram 57 agentes comunitários de saúde (ACS) e 8 ACEs. Todos os participantes informaram realizar orientações ao morador e 58 realizavam controle mecânico durante a vistoria de imóveis, visando evitar e eliminar possíveis criadouros do Aedes aegypti. Quanto à integração dos ACEs na ESF, 18 participantes destacaram o trabalho em equipe como aspecto positivo, enquanto 15 referiram falta de autonomia para intervenções legais como aspecto negativo. Conclusão: A integração do ACE na ESF é viável; contudo, ajustes devem ser realizados para potencializar as atividades, na perspectiva do trabalho compartilhado em uma mesma base territorial.

Objetivo: Describir el proceso de integración del Agente de Combate a las Endemias (ACE) en la Estrategia de Salud Familiar (ESF). Métodos: Estudio descriptivo transversal. Los datos se recopilaron por un cuestionario semiestructurado autoadministrado, de febrero a mayo de 2017, en cuatro Unidades de Salud Familiar en la región urbana de Campo Grande, Mato Grosso do Sul, Brasil. Resultados: Participaran 57 Agentes de Salud Comunitaria (ACS) y 8 ACE. Todos informaron que proporcionaron orientación a los habitantes y 58 realizaron control mecánico durante la inspección de las propiedades, buscando evitar y eliminar posibles sitios de reproducción para Aedes aegypti. En cuanto a la integración de los ACE en la ESF, 18 participantes destacaron el trabajo en equipo como un aspecto positivo, y 15, la falta de autonomía para las intervenciones legales como un aspecto negativo. Conclusión: La integración de los ACE en la ESF es factible, sin embargo, son necesarios ajustes para mejorar las actividades en la perspectiva del trabajo compartido sobre la misma base territorial.

Objective: To describe the process of Endemic Disease Control Worker (EDCW) integration into the Family Health Strategy. Methods: This was a descriptive cross-sectional study. Data were collected through a self-administered semi-structured questionnaire, from February to May 2017, in four Family Health centers in the urban region of Campo Grande, Mato Grosso do Sul, Brazil. Results: 57 Community Health Agents (CHW) and eight EDCWs participated. All participants reported providing guidance to property dwellers and 58 carried out mechanical vector control during the inspection of properties, in order to avoid and eliminate possible Aedes aegypti breeding sites. With regard to EDCW integration in the Family Health Strategy, 18 participants highlighted teamwork as a positive aspect; while 15 highlighted lack of autonomy to undertake legal interventions as a negative aspect. Conclusion: EDCW integration in the Family Health Strategy is feasible, however, adjustments need to be made to optimize activities within the perspective of shared work in the same territorial area.

Decreased risk of cholangiocarcinoma in diabetic patients treated with metformin.

BACKGROUND: Cholangiocarcinoma is an important biliary tract cancer. The high incidence of this cancer is observed in tropical Asia. Several underlying factors are mentioned for this cancer including to diabetes mellitus. The use of the antidiabetic drug, metformin, is mentioned for possibility for decreasing risk for cholangiocarcinoma. METHODS: The work is aimed to estimate the change in risk of local people in the endemic area of cholangiocarcinoma in scenario that diabetic patients are treated with metformin in the highly endemic area of cancer in Thailand. RESULTS: In this study, the authors estimated the change in risk of local people in the endemic area of cholangiocarcinoma in scenario that diabetic patients are treated with metformin. CONCLUSION: The results show a slight decreased risk of cholangiocarcinoma in that scenario.

The impact of mass drug administration on Schistosoma haematobium infection: what is required to achieve morbidity control and elimination?

BACKGROUND: Schistosomiasis remains an endemic parasitic disease causing much morbidity and, in some cases, mortality. The World Health Organization (WHO) has outlined strategies and goals to combat the burden of disease caused by schistosomiasis. The first goal is morbidity control, which is defined by achieving less than 5% prevalence of heavy intensity infection in school-aged children (SAC). The second goal is elimination as a public health problem (EPHP), achieved when the prevalence of heavy intensity infection in SAC is reduced to less than 1%. Mass drug administration (MDA) of praziquantel is the main strategy for control. However, there is limited availability of praziquantel, particularly in Africa where there is high prevalence of infection. It is therefore important to explore whether the WHO goals can be achieved using the current guidelines for treatment based on targeting SAC and, in some cases, adults. Previous modelling work has largely focused on Schistosoma mansoni, which in advance cases can cause liver and spleen enlargement. There has been much less modelling of the transmission of Schistosoma haematobium, which in severe cases can cause kidney damage and bladder cancer. This lack of modelling has largely been driven by limited data availability and challenges in interpreting these data. RESULTS: In this paper, using an individual-based stochastic model and age-intensity profiles of S. haematobium from two different communities, we calculate the probability of achieving the morbidity and EPHP goals within 15 years of treatment under the current WHO treatment guidelines. We find that targeting SAC only can achieve the morbidity goal for all transmission settings, regardless of the burden of infection in adults. The EPHP goal can be achieved in low transmission settings, but in some moderate to high settings community-wide treatment is needed. CONCLUSIONS: We show that the key determinants of achieving the WHO goals are the precise form of the age-intensity of infection profile and the baseline SAC prevalence. Additionally, we find that the higher the burden of infection in adults, the higher the chances that adults need to be included in the treatment programme to achieve EPHP.

Status of parasitological indicators and morbidity burden of onchocerciasis after years of successive implementation of mass distribution of ivermectin in selected communities of Yeki and Asosa districts, Ethiopia.

BACKGROUND: Control and elimination of onchocerciasis requires regular follow-up and evaluation of community directed treatment with ivermectin (CDTi) program implementation. This research was aimed to assess the epidemiological status of onchocerciasis in disease endemic communities of Asosa and Yeki districts of Ethiopia after 5 and 15 years of successive CDTi respectively, and to evaluate the decline in infection and morbidity burden. METHODS: A community-based cross-sectional study was conducted from August 2017 to January 2018 (i.e. within 2-7 months since the last treatment) using interview, physical and parasitological examinations. Pre-CDTi epidemiological data were obtained from studies conducted prior to the launch of CDTi. RESULTS: A total of 3002 individuals (1567 from Asosa and 1435 from Yeki) were included. No infection was detected from Yeki. In Asosa, the prevalence of infection was 1.6%. The geometric mean intensity of infection was 0.02 mf/mg of skin snip. The prevalence rates of dermatitis, depigmentation, nodule, and atrophy in Yeki were 33(2.3%), 57(4%), 37(2.6%) and 11(0.7%), respectively. The prevalence rates of papular dermatitis, depigmentation, palpable nodule, atrophy, and blindness in Asosa were 94(6%), 38(2.4%), 30(1.9%), 28(1.8%) and 2(0.1%), respectively. Five years of CDTi had significantly reduced prevalence and intensity of infection by 91.8% (p < 0.001) and 99.7% (p < 0.001), respectively. Moreover, CDTi reduced prevalence of papular dermatitis by 95.9% (p < 0.001), palpable nodule by 90.5% (p < 0.001), and atrophy by 30% (p = 0.6) in Yeki. Similarly, CDTi reduced prevalence of papular dermatitis by 88.6% (p < 0.001), depigmentation by 90.3% (p < 0.001), atrophy by 89.5% (p < 0.001), and blindness by 90% (p < 0.001) in Asosa. CONCLUSIONS: Fifteen years of successive CDTi had brought the infection from high to zero in Yeki. However, thorough entomological and serological data need to be generated to ascertain whether complete interruption of parasite transmission has been attained, and for considerations of an evidence-based CDTi cessation. Five years of CDTi in Asosa has significantly reduced the infection and morbidity of onchocerciasis to very low level. We, hereby, recommend biannual CDTi to continue in Asosa and its surroundings until the infection transmission is fully interrupted.

Fiabilidad y validación del instrumento de conocimientos, actitudes y prácticas en la enfermedad de Chagas / Reliability and validation of an instrument to measure knowledge, attitudes and practices in response to Chagas disease

RESUMEN Introducción: La enfermedad de Chagas es de alta endemia en Colombia y es considerada un problema de salud pública por la morbilidad y mortalidad que ocasiona. Conocer la percepción de las comunidades frente a esta enfermedad es relevante en cuanto a las estrategias oportunas que se pueden establecer para su prevención. Objetivo: Evaluar la fiabilidad y validez de un instrumento que permita medir los conocimientos, actitudes y prácticas frente a la enfermedad de Chagas en comunidades endémicas. Métodos: Se desarrolló un estudio de corte transversal para la validación del contenido de un instrumento, diseñado con base en la literatura, el cual se sometió a la valoración por un panel de expertos que determinaron la eficiencia, relevancia, claridad y coherencia de cada uno de los ítems. Se determinó el índice Kappa de Randolph para evaluar concordancia. Luego se aplicó a 135 personas de áreas endémicas y se estableció el alfa de Cronbach para determinar consistencia interna. Resultados: El instrumento estudiado demostró concordancia según el índice de Randolph con una Kappa entre 0,7-0,8 para los ítems evaluados, con un alfa de Cronbach de 0,855 lo cual denota una consistencia adecuada. El cuestionario finalmente se estructuró con un total de 27 ítems que abordan: factores epidemiológicos y conocimientos de la enfermedad junto con actitudes y prácticas frente a esta. Conclusiones: El instrumento tiene un nivel adecuado de consistencia interna y concordancia, que permitiría su aplicación en áreas endémicas con poblaciones en riesgo a adquirir la enfermedad de Chagas.

ABSTRACT Introduction: Chagas disease is highly endemic in Colombia and considered to be a public health problem due to its morbidity and mortality. Learning about community perception of this disease is relevant to devise timely strategies for its prevention. Objective: Evaluate the reliability and validity of an instrument to measure knowledge, attitudes and practices in response to Chagas disease in endemic communities. Methods: A cross-sectional study was conducted to validate the content of a tool based on the literature and assessed by an expert panel to determine the efficiency, relevance, clarity, and coherence of each of its items. Determination was made of Randolph's kappa index to evaluate agreement. Then it was applied to 135 people from endemic areas and Cronbach's alpha was established to determine internal consistency. Results: The tool studied showed agreement by Randolph's index with a kappa between 0.7 and 0.8 for the items evaluated and a Cronbach's alpha of 0.855, denoting appropriate consistency. The questionnaire was finally structured with a total 27 items addressing epidemiological factors and knowledge about the disease as well as attitudes and practices in response to it. Conclusions: The tool has an adequate level of internal consistency and agreement, which makes its application advisable in endemic areas with populations at risk of acquiring Chagas disease.

Does mass drug administration affect Schistosoma mansoni infection trends in West Dembia district, Northwest Ethiopia?

INTRODUCTION: Schistosomiasis is one of the Neglected Tropical Diseases in Ethiopia. Since 2015, yearly school-based mass drug administration (MDA) using praziquantel has become the major control strategy. This study aimed to assess trends of Schistosoma mansoni infection in a high-endemic area in Northwest Ethiopia. METHODOLOGY: Data were extracted from routine laboratory logbooks at two health centers in West Dembia district, Amhara region, for the period 2013-2018. Wet-mount direct microscopy was used to diagnose intestinal parasites. Chi-square test was used to compare proportions of S. mansoni-positive results before and after the start of MDA with praziquantel, across sex, age groups, and seasons. RESULTS: Data of 8002 stool tests was extracted. The proportion of S. mansoni progressively decreased from 9.6% in 2013 to 4.1% in 2018 in the overall patient population and from 20.3% in 2013 to 8.8% in 2018 in school-aged children. However, a declining trend of S. mansoni was observed before the launch of MDA and remained constant after the start of the MDA. The positivity rate was significantly higher in males and in the 5-14 years age group. S .mansoni infection in school aged children showed significant seasonal variation. CONCLUSIONS: The declined trend of S. mansoni positivity rate is encouraging and may be related to the existence of intervention packages. Although the timing of MDA was related with low positivity rate of S. mansoni infection, it has not resulted in the expected beneficial effect. Therefore, the district health office should work on both MDA and other interventions.

Contributions and achievements on schistosomiasis control and elimination in China by NIPD-CTDR.

Being a zoonotic parasitic disease, schistosomiasis was widely spread in 12 provinces of Southern China in the 1950s, severly harming human health and hindering economic development. The National Institute of Parasitic Diseases at the Chinese Center for Diseases Control and Prevention, and Chinese Center for Tropical Diseases Research (NIPD-CTDR), as the only professional institution focussing on parasitic diseases at the national level, has played an important role in schistosomiasis control in the country. In this article, we look back at the changes of schistosomiasis endemicity and the contribution of NIPD-CTDR to the national schistosomiasis control programme. We review NIPD-CTDR's activities, including field investigations, design of control strategies and measures, development of diagnostics and drugs, surveillance-response of endemic situation, and monitoring & evaluation of the programme. The NIPD-CTDR has mastered the transmission status of schistosomiasis, mapped the snail distribution, and explored strategies and measures suitable for different types of endemic areas in China. With a good understanding of the life cycle of Schistosoma japonicum and transmission patterns of the disease, advanced research carried out in the NIPD-CTDR based on genomics and modern technology has made it possible to explore highly efficient and soft therapeutic drugs and molluscicides, making it possible to develop new diagnostic tools and produce vaccine candidates. In the field, epidemiological studies, updated strategies and targeted intervention measures developed by scientists from the NIPD-CTDR have contributed significantly to the national schistosomiasis control programme. This all adds up to a strong foundation for eliminating schistosomiasis in China in the near future, and recommendations have been put forward how to reach this goal.

Control of taeniasis and cysticercosis in China.

National surveys suggest that the prevalence of taeniasis has considerably decreased in China, while reported cases indicated T. solium cysticercosis was historically highly endemic in northeastern, central and southwestern China. The high prevalence of taeniasis and cysticercosis there was driven by socio-ecological determinants. Cysticercosis may occur in the central nervous system, spinal cord, subcutaneous muscle, eyes, heart and oral cavity. Neurocysticercosis, the clinically most important type, causes epilepsy, increased intracranial pressure and neuropsychiatric symptoms. New molecular diagnostic techniques have been introduced for high sensitivity and discrimination of Taenia species. Immunological methods remain useful in the diagnosis of cysticercosis, especially neurocysticercosis. The introduction of imaging techniques including computed tomography and magnetic resonance imaging has significantly improved the diagnosis of neurocysticercosis. Recently, a combination of pumpkin seeds and areca nut has been explored against taeniasis, while praziquantel and albendazole are administrated simultaneously against cysticercosis, with promising efficacy and low side-effects. The widespread adoption of deworming protocols and techniques for inspection, management and treatment of pigs as well as improved sewage management has contributed to the significant decrease of taeniasis and cysticercosis in northern China. The positive results of these techniques should now be extended to highly endemic areas in western China to achieve the national elimination target for taeniasis and cysticercosis. Elimination of taeniasis and cysticercosis in China will not only benefit public health within China but also set an important example for less developed countries.