RESUMO
The interplay between cellular and molecular determinants that lead to severe malaria in adults is unexplored. Here, we analyzed parasite virulence factors in an infected adult population in India and investigated whether severe malaria isolates impair endothelial protein C receptor (EPCR), a protein involved in coagulation and endothelial barrier permeability. Severe malaria isolates overexpressed specific members of the Plasmodium falciparum var gene/PfEMP1 (P. falciparum erythrocyte membrane protein 1) family that bind EPCR, including DC8 var genes that have previously been linked to severe pediatric malaria. Machine learning analysis revealed that DC6- and DC8-encoding var transcripts in combination with high parasite biomass were the strongest indicators of patient hospitalization and disease severity. We found that DC8 CIDRα1 domains from severe malaria isolates had substantial differences in EPCR binding affinity and blockade activity for its ligand activated protein C. Additionally, even a low level of inhibition exhibited by domains from two cerebral malaria isolates was sufficient to interfere with activated protein C-barrier protective activities in human brain endothelial cells. Our findings demonstrate an interplay between parasite biomass and specific PfEMP1 adhesion types in the development of adult severe malaria, and indicate that low impairment of EPCR function may contribute to parasite virulence.
Assuntos
Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidade , Proteínas de Protozoários/genética , Adulto , Antígenos CD/genética , Antígenos CD/metabolismo , Biomassa , Receptor de Proteína C Endotelial , Feminino , Humanos , Aprendizado de Máquina , Malária Falciparum/genética , Malária Falciparum/metabolismo , Masculino , Pessoa de Meia-Idade , Proteína C/metabolismo , Domínios Proteicos , Proteínas de Protozoários/química , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Virulência , Adulto JovemRESUMO
BACKGROUND: Culture-adapted Plasmodium falciparum parasites can offer deeper understanding of geographic variations in drug resistance, pathogenesis and immune evasion. To help ground population-based calculations and inferences from culture-adapted parasites, the complete range of parasites from a study area must be well represented in any collection. To this end, standardized adaptation methods and determinants of successful in vitro adaption were sought. METHODS: Venous blood was collected from 33 P. falciparum-infected individuals at Goa Medical College and Hospital (Bambolim, Goa, India). Culture variables such as whole blood versus washed blood, heat-inactivated plasma versus Albumax, and different starting haematocrit levels were tested on fresh blood samples from patients. In vitro adaptation was considered successful when two four-fold or greater increases in parasitaemia were observed within, at most, 33 days of attempted culture. Subsequently, parasites from the same patients, which were originally cryopreserved following blood draw, were retested for adaptability for 45 days using identical host red blood cells (RBCs) and culture media. RESULTS: At a new endemic area research site, ~65% of tested patient samples, with varied patient history and clinical presentation, were successfully culture-adapted immediately after blood collection. Cultures set up at 1% haematocrit and 0.5% Albumax adapted most rapidly, but no single test condition was uniformly fatal to culture adaptation. Success was not limited by low patient parasitaemia nor by patient age. Some parasites emerged even after significant delays in sample processing and even after initiation of treatment with anti-malarials. When 'day 0' cryopreserved samples were retested in parallel many months later using identical host RBCs and media, speed to adaptation appeared to be an intrinsic property of the parasites collected from individual patients. CONCLUSIONS: Culture adaptation of P. falciparum in a field setting is formally shown to be robust. Parasites were found to have intrinsic variations in adaptability to culture conditions, with some lines requiring longer attempt periods for successful adaptation. Quantitative approaches described here can help describe phenotypic diversity of field parasite collections with precision. This is expected to improve population-based extrapolations of findings from field-derived fresh culture-adapted parasites to broader questions of public health importance.
Assuntos
Plasmodium falciparum/citologia , Células Cultivadas , Criopreservação , Eritrócitos/parasitologia , Técnicas de Genotipagem , Humanos , Plasmodium falciparum/genéticaRESUMO
BACKGROUND: Malaria remains an important cause of morbidity and mortality in India. Though many comprehensive studies have been carried out in Africa and Southeast Asia to characterize and examine determinants of Plasmodium falciparum and Plasmodium vivax malaria pathogenesis, fewer have been conducted in India. METHODS: A prospective study of malaria-positive individuals was conducted at Goa Medical College and Hospital (GMC) from 2012 to 2015 to identify demographic, diagnostic and clinical indicators associated with P. falciparum and P. vivax infection on univariate analysis. RESULTS: Between 2012 and 2015, 74,571 febrile individuals, 6287 (8.4%) of whom were malaria positive, presented to GMC. The total number of malaria cases at GMC increased more than two-fold over four years, with both P. vivax and P. falciparum cases present year-round. Some 1116 malaria-positive individuals (mean age = 27, 91% male), 88.2% of whom were born outside of Goa and 51% of whom were construction workers, were enroled in the study. Of 1088 confirmed malaria-positive patients, 77.0% had P. vivax, 21.0% had P. falciparum and 2.0% had mixed malaria. Patients over 40 years of age and with P. falciparum infection were significantly (p < 0.001) more likely to be hospitalised than younger and P. vivax patients, respectively. While approximately equal percentages of hospitalised P. falciparum (76.6%) and P. vivax (78.9%) cases presented with at least one WHO severity indicator, a greater percentage of P. falciparum inpatients presented with at least two (43.9%, p < 0.05) and at least three (29.9%, p < 0.01) severity features. There were six deaths among the 182 hospitalised malaria positive patients, all of whom had P. falciparum. CONCLUSION: During the four year study period at GMC, the number of malaria cases increased substantially and the greatest burden of severe disease was contributed by P. falciparum.
Assuntos
Malária Falciparum/patologia , Malária Vivax/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Demografia , Feminino , Humanos , Incidência , Índia/epidemiologia , Lactente , Malária Falciparum/diagnóstico , Malária Falciparum/epidemiologia , Malária Vivax/diagnóstico , Malária Vivax/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Centros de Atenção Terciária , Adulto JovemRESUMO
Kikuchi's disease is a rare condition that mainly presents in young females along with lymphadenitis. Involvement of the nervous system is rare. We report a young female who presented with fever, headache, vomiting, lymphadenopathy and neurological manifestations in the form of aseptic meningitis, ataxia and paraparesis. Since the disease can be mistaken clinically and histologically for SLE, lymphoma and tuberculosis it is important to differentiate it from these conditions. Also our case emphasizes the importance of recognising this disorder in diagnosing patients with meningitis.
Assuntos
Ataxia/etiologia , Linfadenite Histiocítica Necrosante/complicações , Linfonodos/patologia , Meningite Asséptica/etiologia , Paraparesia/etiologia , Adolescente , Ataxia/diagnóstico , Biópsia , Diagnóstico Diferencial , Feminino , Linfadenite Histiocítica Necrosante/diagnóstico , Humanos , Meningite Asséptica/diagnóstico , Paraparesia/diagnósticoRESUMO
Drug hypersensitivity with myocarditis is known to occur with many drugs especially with antiepileptics, sulpha-compounds and daposne. Dapsone (4, 4 diaminodiphenyl sulphone) induced hypersensitivity is known to occur in about 2% of leprosy patients on treatment and an incidence of 1.66% in non-leprosy patients. We report this rare case of dapsone hypersensitivity syndrome in a girl on dapsone who presented with fever, anaemia, jaundice, skin rash, lymphadenopathy, and hepatomegaly and later developed myocarditis. The drug was withdrawn and the patient was treated with steroids. She improved and was discharged. She relapsed after the corticosteroids were discontinued at home.
Assuntos
Dapsona/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Miocardite/etiologia , Adolescente , Hipersensibilidade a Drogas/complicações , Feminino , HumanosRESUMO
Over the last decade, novel tobacco and nicotine product experimentation and use have dramatically increased among the youth, even in countries with strong tobacco control and anti-smoking social norms. We performed an online questionnaire-based cross-sectional study in March-June 2021, targeting students from the University of Beira Interior, Portugal. The aim was to assess the experimentation and use of tobacco and nicotine products and students' beliefs towards these products. Of the 452 participants, 67.0% were female; the mean age was 21.9 ± 3 years. Most students (60.4%) reported experimenting with tobacco/nicotine products; 31.2% were current users; polyconsumption was common. Of the current users, all used cigarettes, 41.1% used heated tobacco, 20.6% e-cigarettes, and 14.9% used water pipes. Our multivariate analysis showed that being male, being in the third year of study, and cohabiting or socializing with smokers were strongly associated with tobacco/nicotine use. While most students agree that heated tobacco and e-cigarettes are addictive, that they are not less harmful than cigarettes, and that second-hand exposure may cause health problems, few tobacco/nicotine users are ready to quit, and few students support a smoke-free university campus. These findings indicate high experimentation and the regular dual use of novel tobacco and nicotine products and suggest a pro-smoking social norm among university students.
Assuntos
Estudantes , Humanos , Feminino , Masculino , Portugal/epidemiologia , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Universidades , Adulto Jovem , Estudos Transversais , Adulto , Inquéritos e Questionários , Adolescente , Produtos do Tabaco , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , COVID-19/psicologia , COVID-19/epidemiologiaRESUMO
The South Asia International Center of Excellence for Malaria Research, an NIH-funded collaborative program, investigated the epidemiology of malaria in the Indian state of Goa through health facility-based data collected from the Goa Medical College and Hospital (GMC), the state's largest tertiary healthcare facility, between 2012 and 2021. Our study investigated region-specific spatial and temporal patterns of malaria transmission in Goa and the factors driving such patterns. Over the past decade, the number of malaria cases, inpatients, and deaths at the GMC decreased significantly after a peak in 2014-2015. However, the proportion of severe malaria cases increased over the study period. Also, a trend of decreasing average parasitemia and increasing average gametocyte density suggests a shift toward submicroscopic infections and an increase in transmission commitment characteristic of low-transmission regions. Although transmission occurred throughout the year, 75% of the cases occurred between June and December, overlapping with the monsoon (June-October), which featured rainfall above yearly average, minimal diurnal temperature variation, and high relative humidity. Sociodemographic factors also had a significant association with malaria cases, with cases being more frequent in the 15-50-year-old age group, men, construction workers, and people living in urban areas within the GMC catchment region. Our environmental model of malaria transmission projects almost negligible transmission at the beginning of 2025 (annual parasitic index: 0.0095, 95% CI: 0.0075-0.0114) if the current control measures continue undisrupted.
Assuntos
Malária , Humanos , Índia/epidemiologia , Adolescente , Feminino , Adulto , Masculino , Criança , Pessoa de Meia-Idade , Adulto Jovem , Pré-Escolar , Lactente , Malária/transmissão , Malária/epidemiologia , Malária/prevenção & controle , Idoso , Estações do Ano , Hospitais/estatística & dados numéricos , Erradicação de Doenças , Malária Falciparum/epidemiologia , Malária Falciparum/transmissão , Malária Falciparum/prevenção & controleRESUMO
BACKGROUND & OBJECTIVES: Scrub typhus is one of the differential diagnoses of haemorrhagic fevers especially if associated with jaundice and/or renal failure. Goa State in the western region of India has been witnessing increased incidence of such fevers, therefore, the present study was undertaken to identify whether scrub typhus is the aetiological agent. METHODS: Adult patients presenting with undiagnosed febrile illness between June 2009 to October 2010, were evaluated. Testing was done using a commercial ELISA kit for specific IgM antibodies against Orientia tsutsugamushi. RESULTS: Of the 44 patients included in the study, 15 (34%) were found to be positive for IGM antibodies against O. tsutsugamushi. The cases were seen mainly in the months between July to November. The common symptoms noted were fever, myalgias, gastrointestinal complaints, followed by breathlessness, rash and jaundice. The pathognomonic features such as eschar and lymphadenopathy were seen only in two patients. Nearly two third of the patients had leukocytosis (67%) and low serum albumin (60%). The most common complication noticed was hepatitis (80%) followed by acute respiratory distress syndrome (ARDS) (60%), thrombocytopenia (40%) and acute renal failure (33%). Five patients died in the course of illness. INTERPRETATION & CONCLUSIONS: Our results showed that scrub typhus should be considered in the differential diagnosis of acute febrile illness associated with gastrointestinal symptoms, rash, myalgia , including those with organ dysfunctions such as hepatorenal syndrome, coagulopathy or ARDS. Empirical treatment with doxycycline or macrolides may be given in cases with strong suspicion of scrub typhus.
Assuntos
Febre/etiologia , Orientia tsutsugamushi/imunologia , Tifo por Ácaros/epidemiologia , Tifo por Ácaros/patologia , Adulto , Diagnóstico Diferencial , Doxiciclina/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina M/sangue , Incidência , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Tifo por Ácaros/diagnóstico , Tifo por Ácaros/tratamento farmacológicoRESUMO
The clinical presentation of severe Plasmodium falciparum malaria differs between children and adults, but the mechanistic basis for this remains unclear. Contributing factors to disease severity include total parasite biomass and the diverse cytoadhesive properties mediated by the polymorphic var gene parasite ligand family displayed on infected erythrocytes. To explore these factors, we performed a multicohort analysis of the contribution of var expression and parasite biomass to severe malaria in two previously published pediatric cohorts in Tanzania and Malawi and an adult cohort in India. Machine learning analysis revealed independent and complementary roles for var adhesion types and parasite biomass in adult and pediatric severe malaria and showed that similar var profiles, including upregulation of group A and DC8 var, predict severe malaria in adults and children. Among adults, patients with multiorgan complications presented infections with significantly higher parasite biomass without significant differences in var adhesion types. Conversely, pediatric patients with specific complications showed distinct var signatures. Cerebral malaria patients showed broadly increased expression of var genes, in particular group A and DC8 var, while children with severe malaria anemia were classified based on high transcription of DC8 var only. This study represents the first large multisite meta-analysis of var expression, and it demonstrates the presence of common var profiles in severe malaria patients of different ages across distant geographical sites, as well as syndrome-specific disease signatures. The complex associations between parasite biomass, var adhesion type, and clinical presentation revealed here represent the most comprehensive picture so far of the relationship between cytoadhesion, parasite load, and clinical syndrome.IMPORTANCEP. falciparum malaria can cause multiple disease complications that differ by patient age. Previous studies have attempted to address the roles of parasite adhesion and biomass in disease severity; however, these studies have been limited to single geographical sites, and there is limited understanding of how parasite adhesion and biomass interact to influence disease manifestations. In this meta-analysis, we compared parasite disease determinants in African children and Indian adults. This study demonstrates that parasite biomass and specific subsets of var genes are independently associated with detrimental outcomes in both childhood and adult malaria. We also explored how parasite var adhesion types and biomass play different roles in the development of specific severe malaria pathologies, including childhood cerebral malaria and multiorgan complications in adults. This work represents the largest study to date of the role of both var adhesion types and biomass in severe malaria.
Assuntos
Variação Genética , Genótipo , Malária Falciparum/patologia , Malária Falciparum/parasitologia , Plasmodium falciparum/classificação , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Índia , Lactente , Aprendizado de Máquina , Malaui , Masculino , Carga Parasitária , TanzâniaRESUMO
Background & objectives: Scrub typhus is one of the differential diagnoses of haemorrhagic fevers especially if associated with jaundice and/or renal failure. Goa State in the western region of India has been witnessing increased incidence of such fevers, therefore, the present study was undertaken to identify whether scrub typhus is the aetiological agent. Methods: Adult patients presenting with undiagnosed febrile illness between June 2009 to October 2010, were evaluated. Testing was done using a commercial ELISA kit for specific IgM antibodies against Orientia tsutsugamushi. Results: Of the 44 patients included in the study, 15 (34%) were found to be positive for IGM antibodies against O. tsutsugamushi. The cases were seen mainly in the months between July to November. The common symptoms noted were fever, myalgias, gastrointestinal complaints, followed by breathlessness, rash and jaundice. The pathognomonic features such as eschar and lymphadenopathy were seen only in two patients. Nearly two third of the patients had leukocytosis (67%) and low serum albumin (60%). The most common complication noticed was hepatitis (80%) followed by acute respiratory distress syndrome (ARDS) (60%), thrombocytopenia (40%) and acute renal failure (33%). Five patients died in the course of illness. Interpretation & conclusions: Our results showed that scrub typhus should be considered in the differential diagnosis of acute febrile illness associated with gastrointestinal symptoms, rash, myalgia , including those with organ dysfunctions such as hepatorenal syndrome, coagulopathy or ARDS. Empirical treatment with doxycycline or macrolides may be given in cases with strong suspicion of scrub typhus.
RESUMO
A obesidade é uma doença multifatorial de prevalência crescente e vem adquirindo proporções alarmantemente epidêmicas, sendo um dos principais problemas de saúde pública da sociedade moderna. É uma doença crônica não transmissível caracterizada pelo acúmulo excessivo de energia, sob a forma de triglicerídeos, no tecido adiposo distribuído pelo corpo, podendo gerar prejuízos à saúde dos indivíduos. A orientação dietética, a programação de atividade física e o uso de fármacos são os pilares principais do tratamento. A cirurgia bariátrica tem sido utilizada como recurso, com a intenção de promover a redução da ingestão energética, perda de peso, melhoria da qualidade de vida e comorbidades associadas. Após a realização desse procedimento, ocorre importante redução no consumo alimentar, principalmente de calorias, proteínas, vitaminas e minerais, podendo ser inferior a 50% das suas necessidades nutricionais. Um dos efeitos colaterais após a cirurgia é a intolerância alimentar, ocasionando os sintomas comuns do pós-operatório como vômito, diarreia, constipação e síndrome de Dumping. Desta maneira, faz-se necessária adequada avaliação das intolerâncias alimentares a fim de minimizar as deficiências nutricionais e melhorar aceitação da dieta e qualidade de vida do paciente pós-operatório de cirurgia bariátrica.
Obesity is a multifactorial disorder and prevalence is increasing at an alarming rate. Today this disease is one of the main public health problems. It is non communicable chronic disease (NCD) characterized by excess fat accumulation in the form of triglycerides in adipose tissue distributed throughout body, and can cause serious damage to health. Many different type of treatment has been used as dietary guidance, physical activity and drugs. Bariatric surgery is a procedure used to promote reduction of energy intake, weight loss, quality of life and associated comorbidities. Afterwards surgery, there is a significant reduction in food consumption, especially of calories, protein, vitamins and minerals may be less than 50% of their nutritional requirements. After surgery, food intolerance is one of the most common side effects, leading to common symptoms of postoperative as vomiting, diarrhea, constipation and Dumping Syndrome. Thus, it is necessary appropriate evaluate of food intolerances in order to minimize nutritional deficiencies and improve acceptance of food and quality of life after bariatric surgery.