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Electrical excitability-the ability to fire and propagate action potentials-is a signature feature of neurons. How neurons become excitable during development and whether excitability is an intrinsic property of neurons remain unclear. Here, we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development. We find that Schwann cells secrete prostaglandin E2, which is necessary and sufficient to induce developing somatosensory neurons to express normal levels of genes required for neuronal function, including voltage-gated sodium channels, and to fire action potential trains. Inactivating this signaling pathway in Schwann cells impairs somatosensory neuron maturation, causing multimodal sensory defects that persist into adulthood. Collectively, our studies uncover a neurodevelopmental role for prostaglandin E2 distinct from its established role in inflammation, revealing a cell non-autonomous mechanism by which glia regulate neuronal excitability to enable the development of normal sensory functions.
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Potenciales de Acción , Dinoprostona , Células de Schwann , Células Receptoras Sensoriales , Animales , Células de Schwann/metabolismo , Dinoprostona/metabolismo , Ratones , Células Receptoras Sensoriales/metabolismo , Transducción de SeñalRESUMEN
In Vietnam and the Philippines, viral hepatitis is the leading cause of cirrhosis and liver cancer. This study aims to understand the barriers and enablers of people receiving care for hepatitis B and C to support both countries' efforts to eliminate viral hepatitis as a public health threat by 2030. Retrospective, semi-structured interviews were conducted with a purposive, quota-based sample of 63 people living with hepatitis B or C in one province of Vietnam and one region of the Philippines. A rapid deductive approach to thematic analysis produced key findings among the three phases of care: (1) pre-awareness and testing, (2) linkage and treatment initiation and (3) ongoing treatment and recovery. The research found that participants followed five typical journeys, from a variety of entry points. Barriers during the pre-awareness and testing phase included limited awareness about hepatitis and its management, stigma and psychological impacts. Enablers included being familiar with the health system and/or patients benefiting from social connections within the health systems. During the linkage and treatment initiation phase, barriers included difficult physical access, complex navigation and inadequate counselling. In this phase, family support emerged as a critical enabler. During the ongoing treatment and recovery phase, the cost of care and socially and culturally informed perceptions of the disease and medication use were both barriers and enablers. Exploring peoples' journeys with hepatitis B and C in Vietnam and the Philippines revealed many similarities despite the different cultural and health system contexts. Insights from this study may help generate a contextualized, people-centred evidence base to inform the design and improvement of primary care services for hepatitis in both research sites.
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Accesibilidad a los Servicios de Salud , Humanos , Vietnam/epidemiología , Filipinas/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Anciano , Hepatitis B , Entrevistas como Asunto , Adulto Joven , Hepatitis C/epidemiología , Hepatitis C/tratamiento farmacológicoRESUMEN
Background: This study aimed to evaluate the clinical characteristics, patient's management approaches, and outcomes of the COVID-19 patients in Phu Tho Province, Vietnam. Methods: A retrospective, multicenter study of 2166 COVID-19 patients in 13 hospitals in Phutho Province, Vietnam. The subjects were divided into 3 groups based on vaccination status: unvaccinated group, 1st dose of vaccine group, 2nd dose of vaccine group. The clinical characteristics, management approaches, and outcomes were collected and compared between the 3 groups. Results: The hospitalization rate of the 3 groups decreased from the unvaccinated group, the 1st dose of vaccinated group, to the 2nd dose of vaccinated group, 42.61%; 30,24% and 27,15% respectively. The 19-40 years old group had the highest hospitalization rate (38,1%) together with the group that had not accepted the full COVID 19 vaccination dose (57,64%). The 2nd dose of vaccinated group had the lowest percentages of high temperature, cough, dyspnea, chest pain and sore throat. The unvaccinated group had the highest heart rate, respiratory rate and SpO2 compared to the two other groups. The percentage needing Immunomodulation and Anticoagulant Therapy was highest (6.8% and 1.4 % respectively) in the unvaccinated group. The percentage receiving Antiviral Therapy was highest (42,5%) in those who had received the 2nd dose of vaccine. Conclusions: COVID-19 vaccination improved the symptoms of the patients and should be accepted in all ages.
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COVID-19 , Hospitalización , SARS-CoV-2 , Humanos , Vietnam/epidemiología , COVID-19/epidemiología , Masculino , Adulto , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Hospitalización/estadística & datos numéricos , Adulto Joven , Vacunas contra la COVID-19/administración & dosificación , Anciano , Adolescente , Vacunación/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricosRESUMEN
BACKGROUND: Several nations around the world have utilized autologous immune enhancement therapy in the treatment of cancer, with initial positive outcomes. This study describes our experience with autologous gamma delta T cell immunotherapy for the treatment of non-small cell lung cancer patients in Vietnam, a developing nation. METHODS: Five patients with non-small cell lung cancer at stages III - IV were enrolled in the study. Each patient received six infusions of autologous γδT cells, separated by two weeks. Before, during, at the end of treatment, and three and six months after treatment, a comprehensive evaluation of clinical, laboratory, quality of life, and adverse events related to the method was conducted. RESULTS: At the time of culture seeding, the total number of cells ranged from 2.9 to 18.2 x 106, with γδT cells ranging in number from 10.7 to 19.6 x 104. On day 14 of the culture, the number of γδT cells ranged from 3.1 to 8.3 x 108. Regarding the safety of therapy in a total of 30 infusions, two (fever), one (myalgia), and one (joint pain) were graded as 1 by CTCAE criteria. After the course, no toxicity was observed in the hematopoietic system, kidney function, or liver function. Evaluation of the patient's response in accordance with the RECIST 1.1 criteria: 20% of patients (one patient) had partial response disease, and 80% of patients (four patients) had stable disease at the end of treatment. During the follow-up period of the study, three patients were still alive, and the disease remained stable. The patient's quality of life improved after treatment in most functional measures (activity, cognitive, and social), but physical and emotional scores decreased slightly. Two patients' fatigue symptoms increased, but after six months of treatment, the average value dropped from 25.3 to 8.3. Dyspnea symptoms decreased gradually from 33.3 at the start of treatment to 8.3 six months later. CONCLUSIONS: The initial results we obtained regarding the efficacy and safety of autologous γδT cell immunotherapy for patients with non-small cell lung cancer are extremely encouraging and comparable to those of previous studies.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Ácido Zoledrónico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Calidad de Vida , Inmunoterapia/métodos , Linfocitos TRESUMEN
OBJECTIVE: To assess the nutritional status, growth parameters and lifestyle behaviours of children between 0·5 and 12 years in nationally representative samples in Malaysia, Indonesia, Thailand and Vietnam. DESIGN: A cross-sectional study was conducted in the four countries, between May 2019 and April 2021. Data collected can be categorised into four categories: (1) Growth - anthropometry, body composition, development disorder, (2) nutrient intake and dietary habits - 24-h dietary recall, child food habits, breast-feeding and complementary feeding, (3) socio-economic status - food insecurity and child health status/environmental and (4) lifestyle behaviours - physical activity patterns, fitness, sunlight exposure, sleep patterns, body image and behavioural problems. Blood samples were also collected for biochemical and metabolomic analyses. With the pandemic emerging during the study, a COVID-19 questionnaire was developed and implemented. SETTING: Both rural and urban areas in Malaysia, Indonesia, Thailand and Vietnam. PARTICIPANTS: Children who were well, with no physical disability or serious infections/injuries and between the age of 0·5 and 12 years old, were recruited. RESULTS: The South East Asian Nutrition Surveys II recruited 13 933 children. Depending on the country, data collection from children was conducted in schools and commune health centres, or temples, or sub-district administrative organisations. CONCLUSIONS: The results will provide up-to-date insights into nutritional status and lifestyle behaviours of children in the four countries. Subsequently, these data will facilitate exploration of potential gaps in dietary intake among Southeast Asian children and enable local authorities to plan future nutrition and lifestyle intervention strategies.
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COVID-19 , Estilo de Vida , Encuestas Nutricionales , Estado Nutricional , Humanos , Estudios Transversales , Femenino , Masculino , Preescolar , Niño , Lactante , Vietnam/epidemiología , Indonesia/epidemiología , COVID-19/epidemiología , SARS-CoV-2 , Asia Sudoriental , Malasia/epidemiología , Conducta Alimentaria , Tailandia/epidemiología , Dieta/estadística & datos numéricos , Fenómenos Fisiológicos Nutricionales Infantiles , Pueblos del Este de AsiaRESUMEN
OBJECTIVE: Vietnam is an LMIC in Asia that is experiencing rising cases of Alzheimer's disease and related dementias (ADRD). Many Vietnamese adults at risk of ADRD have experienced early-life war exposures, which may have negative impacts on their cognitive function in later years. METHODS: Our study uses the Vietnam Health and Aging Study (VHAS) to investigate the impact of early-life war exposure on cognitive function in later life while also considering variations in social engagement. The sample consists of 2352 adults aged 60 and older from northern and central Vietnam. Cognitive function, measured by questions from the Mini Mental State Examination (MMSE), and self-rated memory are our dependent variables and five measures related to social engagement serve as independent variables. RESULTS: Our results show an association between PTSD symptoms and poorer cognitive function (0.0704, p < 0.05) and self-rated memory (OR = 0.904, p < 0.001; 95%). Similar results are also found among for individuals with lower level of social engagement. Furthermore, several sociodemographic factors exhibit attenuated effects on cognitive function due to variations in social engagement. CONCLUSION: Social engagement is generally beneficial for cognitive health amongst those with early-life war exposure, but it does not necessarily attenuate the effects of trauma.
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Omicron and its subvariants have steadily gained greater capability of immune escape compared to other variants of concern, resulting in an increased incidence of reinfections even among vaccinated individuals. We evaluated the antibody response to Omicron BA.1, BA.2, and BA.4/5 in US military members vaccinated with the primary 2-dose series of Moderna mRNA-1273 in a cross-sectional study. While nearly all vaccinated participants had sustained spike (S) IgG and neutralizing antibodies (ND50) to the ancestral strain, only 7.7% participants had detectable ND50 to Omicron BA.1 at 8 months postvaccination. The neutralizing antibody response to BA.2 and BA.5 was similarly reduced. The reduced antibody neutralization of Omicron correlated with the decreased antibody binding to the receptor-binding domain. The participants' seropositivity to the nuclear protein positively correlated with ND50. Our data emphasizes the need for continuous vigilance in monitoring for emerging variants and the need to identify potential alternative targets for vaccine design.
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COVID-19 , Personal Militar , Humanos , Vacuna nCoV-2019 mRNA-1273 , Formación de Anticuerpos , Estudios Transversales , SARS-CoV-2/genética , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
Current antibody (Ab) therapies require development of stable formulations and an optimal delivery system. Here, we present a new strategy to create a single-administration long-lasting Ab-delivery microarray (MA) patch, which can carry high doses of thermally stabilized Abs. The MA fabricated by an additive three-dimensional manufacturing technology can be fully embedded into the skin via a single application to deliver doses of Abs at multiple programmable time points, thus sustaining Ab concentrations in systemic circulation. We developed an MA formulation that stabilized and delivered human immunoglobulins (hIg) in a time-controlled manner while maintaining their structure and functionality. As an example, the b12 Abâa broadly neutralizing Ab against HIV-1âmaintained antiviral activity in vitro after MA manufacturing and heat exposure. Pharmacokinetic studies of MA patch-delivered hIg in rats successfully provided a proof of concept for concurrent and time-delayed Ab delivery. These MA patches codeliver different Abs, providing a tool for expanded protection against viral infections or combination HIV therapy and prevention.
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Anticuerpos , Infecciones por VIH , Humanos , Ratas , Animales , Piel , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & controlRESUMEN
OBJECTIVE: Fluid shear stress (FSS) is known to mediate multiple phenotypic changes in the endothelium. Laminar FSS (undisturbed flow) is known to promote endothelial alignment to flow, which is key to stabilizing the endothelium and rendering it resistant to atherosclerosis and thrombosis. The molecular pathways responsible for endothelial responses to FSS are only partially understood. In this study, we determine the role of PGC1α (peroxisome proliferator gamma coactivator-1α)-TERT (telomerase reverse transcriptase)-HMOX1 (heme oxygenase-1) during shear stress in vitro and in vivo. Approach and Results: Here, we have identified PGC1α as a flow-responsive gene required for endothelial flow alignment in vitro and in vivo. Compared with oscillatory FSS (disturbed flow) or static conditions, laminar FSS (undisturbed flow) showed increased PGC1α expression and its transcriptional coactivation. PGC1α was required for laminar FSS-induced expression of TERT in vitro and in vivo via its association with ERRα(estrogen-related receptor alpha) and KLF (Kruppel-like factor)-4 on the TERT promoter. We found that TERT inhibition attenuated endothelial flow alignment, elongation, and nuclear polarization in response to laminar FSS in vitro and in vivo. Among the flow-responsive genes sensitive to TERT status, HMOX1 was required for endothelial alignment to laminar FSS. CONCLUSIONS: These data suggest an important role for a PGC1α-TERT-HMOX1 axis in the endothelial stabilization response to laminar FSS.
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Células Endoteliales/enzimología , Hemo-Oxigenasa 1/metabolismo , Mecanotransducción Celular , Proteínas de la Membrana/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Telomerasa/metabolismo , Animales , Células Cultivadas , Células Endoteliales/patología , Transición Epitelial-Mesenquimal , Femenino , Regulación Enzimológica de la Expresión Génica , Hemo-Oxigenasa 1/genética , Células Endoteliales de la Vena Umbilical Humana/enzimología , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Masculino , Proteínas de la Membrana/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Flujo Sanguíneo Regional , Estrés Mecánico , Telomerasa/genéticaRESUMEN
The formation of silicate oligomers in the early stages is key to zeolite synthesis. The pH and the presence of hydroxide ions are important in regulating the reaction rate and the dominant species in solutions. This paper describes the formation of silicate species, from dimers to 4-membered rings, using ab initio molecular dynamics simulations in explicit water molecules with an excess hydroxide ion. The thermodynamic integration method was used to calculate the free energy profile of the condensation reactions. The hydroxide group's role is not only to control the pH of the environment, but also to actively participate in the condensation reaction. The results show that the most favorable reactions are linear-tetramer and 4-membered-ring formation, with overall barriers of 71 kJ mol-1 and 73 kJ mol-1, respectively. The formation of trimeric silicate, with the largest free-energy barrier of 102 kJ mol-1, is the rate-limiting step under these conditions. The excess hydroxide ion aids in the stabilization of the 4-membered-ring structure over the 3-membered-ring structure. Due to a relatively high free-energy barrier, the 4-membered ring is the most difficult of the small silicate structures to dissolve in the backward reaction. This study is consistent with the experimental observation that silicate growth in zeolite synthesis is slower in a very-high-pH environment.
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Piezoelectric materials, a type of "smart" material that generates electricity while deforming and vice versa, have been used extensively for many important implantable medical devices such as sensors, transducers, and actuators. However, commonly utilized piezoelectric materials are either toxic or nondegradable. Thus, implanted devices employing these materials raise a significant concern in terms of safety issues and often require an invasive removal surgery, which can damage directly interfaced tissues/organs. Here, we present a strategy for materials processing, device assembly, and electronic integration to 1) create biodegradable and biocompatible piezoelectric PLLA [poly(l-lactic acid)] nanofibers with a highly controllable, efficient, and stable piezoelectric performance, and 2) demonstrate device applications of this nanomaterial, including a highly sensitive biodegradable pressure sensor for monitoring vital physiological pressures and a biodegradable ultrasonic transducer for blood-brain barrier opening that can be used to facilitate the delivery of drugs into the brain. These significant applications, which have not been achieved so far by conventional piezoelectric materials and bulk piezoelectric PLLA, demonstrate the PLLA nanofibers as a powerful material platform that offers a profound impact on various medical fields including drug delivery, tissue engineering, and implanted medical devices.
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Implantes Absorbibles , Sistemas Microelectromecánicos/instrumentación , Nanofibras/química , Transductores , Sistemas de Liberación de Medicamentos , Electricidad , Electrónica , Diseño de Equipo , Monitoreo Fisiológico/instrumentación , Presión , Prótesis e Implantes , Ingeniería de Tejidos , UltrasonidoRESUMEN
The objective of this study was to propose a new coating film for biodegradable polymers and environmentally friendly processing. Here, a novel implementation of solid lipid nanoparticles (SLN) into a biodegradable alginate (ALG) film composition created a new gastric-resistant film for an enteric-release tablet. Experiments were performed on a water-soluble substance (thiamine nitrate) to characterize the effects of SLN upon the addition of the ALG coating formulation. The coated tablets or cast films were characterized based on delayed-release properties, surface morphology, moisture resistance, and chemical interactions. The SLN-ALG film displayed gastric-resistant properties (< 10% drug substance dissolved at pH 1.2) and rapid disintegration in the intestinal medium (pH 6.8). Morphological analysis using a microscope and scanning electron microscope confirmed the uniformity and smoothness of the SLN-ALG film, which improved the mechanical properties of the film. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated that SLN contributed to the formation of the film, which maintained free carboxylic groups, making the SLN-ALG film a higher acid resistance, but soluble in pH 6.8 buffer. These promising results suggest a novel nanotechnology-based coating formulation for various enteric-release dosage forms. Because of their biodegradability, the proposed ingredients and processes are safe and environment-friendly.
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Alginatos , Polímeros , Alginatos/química , Comprimidos , Agua/química , Ácidos , Comprimidos Recubiertos/químicaRESUMEN
The COVID-19 outbreak has had serious impact on remote education and service-learning implementation in Taiwan. To alleviate these impacts, the Digital Learning Companion, an online tutoring project, was proposed to bridge the digital divide and learning gap among remote children, while offering university students an online service-learning environment. This project recruited international students as tutors for local children. To explore tutors' perceptions of this project during the COVID-19 pandemic, qualitative research, particularly a case study, was conducted. Adopting purposive sampling, 15 participants were chosen for interviews at the end of the project, and 10 reflective videos were used to reveal further information to supplement the interview results. Content analysis was employed to analyse the data. The findings implied that using JoinNet and tutoring journals significantly facilitated the tutoring process, which led to tutors' remarkable development in skills, social relationships, multicultural experience, altruism, social responsibility, self-efficacy, and affective values. However, they encountered some challenges, such as technical problems, communication barrier, lack of tutee information, and short tutoring duration. The solutions to these challenges and insightful suggestions for the project development are pointed out. The results of this study contribute to tutors' cognitive, social, and motivational development, and support the online service-learning-integrated curriculum, which can become a reference for further studies regarding online service-learning implementation to bridge the research gap.
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Poly-ADP-ribosyltransferases play a critical role in DNA repair and cell death, and poly(ADP-ribosyl) polymerase 1 (PARP1) is a particularly important therapeutic target for the treatment of breast cancer because of its synthetic lethal relationship with breast cancer susceptibility proteins 1 and 2. Numerous PARP1 inhibitors have been developed, and their efficacy in cancer treatment is attributed to both the inhibition of enzymatic activity and their ability to trap PARP1 on to the damaged DNA, which is cytotoxic. Of the clinical PARP inhibitors, talazoparib is the most effective at trapping PARP1 on damaged DNA. Biochemically, talazoparib is also suspected to be a potent inhibitor of PARP5a/b (tankyrase1/2 [TNKS1/2]), which is an important regulator of Wnt/ß-catenin pathway. Here we show using competition experiments in cell lysate that, at a clinically relevant concentration, talazoparib can potentially bind and engage TNKS1. Using surface plasmon resonance, we measured the dissociation constants of talazoparib, olaparib, niraparib, and veliparib for their interaction with PARP1 and TNKS1. The results show that talazoparib has strong affinity for PARP1 as well as uniquely strong affinity for TNKS1. Finally, we used crystallography and hydrogen deuterium exchange mass spectroscopy to dissect the molecular mechanism of differential selectivity of these PARP1 inhibitors. From these data, we conclude that subtle differences between the ligand-binding sites of PARP1 and TNKS1, differences in the electrostatic nature of the ligands, protein dynamics, and ligand conformational energetics contribute to the different pharmacology of these PARP1 inhibitors. These results will help in the design of drugs to treat Wnt/ß-catenin pathway-related cancers, such as colorectal cancers.
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Neoplasias de la Mama/tratamiento farmacológico , Poli(ADP-Ribosa) Polimerasa-1/genética , Tanquirasas/genética , Antineoplásicos/farmacología , Bencimidazoles/farmacología , Sitios de Unión/efectos de los fármacos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Daño del ADN/efectos de los fármacos , Reparación del ADN/genética , Femenino , Humanos , Indazoles/farmacología , Ligandos , Ftalazinas/farmacología , Piperidinas/farmacología , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
BACKGROUND: Malaria rapid diagnostic tests (RDTs) remain the main point-of-care tests for diagnosis of symptomatic Plasmodium falciparum malaria in endemic areas. However, parasites with gene deletions in the most common RDT target, histidine rich protein 2 (pfhrp2/HRP2), can produce false-negative RDT results leading to inadequate case management. The objective of this study was to determine the prevalence of hrp2/3 deletions causing false-negative RDT results in Vietnam (Gia Lai and Dak Lak provinces). METHODS: Individuals presenting with malaria symptoms at health facilities were screened for P. falciparum infection using light microscopy and HRP2-RDT (SD Bioline Malaria Antigen Pf/Pv RDT, Abbott). Microscopically confirmed P. falciparum infections were analysed for parasite species by 18S rRNA qPCR, and pfhrp2 and pfhrp3 exon2 deletions were investigated by nested PCR. pfhrp2 amplicons were sequenced by the Sanger method and HRP2 plasma levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The prevalence of false-negative RDT results among symptomatic cases was 5.6% (15/270). No pfhrp2 and pfhrp3 deletions were identified. False-negative RDT results were associated with lower parasite density (p = 0.005) and lower HRP2 plasma concentrations (p < 0.001), as compared to positive RDT. CONCLUSIONS: The absence of hrp2/3 deletions detected in this survey suggests that HRP2-based malaria RDTs remain effective for the diagnosis of symptomatic P. falciparum malaria in Central Vietnam.
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Malaria Falciparum , Plasmodium falciparum , Humanos , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Eliminación de Gen , Vietnam/epidemiología , Pruebas Diagnósticas de Rutina/métodos , Malaria Falciparum/diagnóstico , Malaria Falciparum/epidemiología , Malaria Falciparum/genética , Antígenos de Protozoos/genética , Antígenos de Protozoos/metabolismo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Malaria elimination by 2030 is an aim of many countries in the Greater Mekong Sub-region, including Vietnam. However, to achieve this goal and accelerate towards malaria elimination, countries need to determine the extent and prevalence of asymptomatic malaria as a potential reservoir for malaria transmission and the intensity of malaria transmission. The purpose of this study was to determine the prevalence of asymptomatic malaria and seropositivity rate in several districts of Gia Lai province in the Central Highlands of Vietnam. METHODS: A cross-sectional survey of asymptomatic malaria and serological testing was conducted in 3283 people living at 14 communes across seven districts in Gia Lai province in December 2016 to January 2017. Finger prick capillary blood samples were tested for malaria using rapid diagnostic testing and polymerase chain reaction (PCR), as well as detecting antibodies against 3 Plasmodium falciparum and 4 Plasmodium vivax antigens by indirect enzyme-linked immunosorbent assay (ELISA). Age-seroprevalence curves were fitted using reverse catalytic models with maximum likelihood. RESULTS: The study population was predominantly male (65.9%, 2165/3283), adults (88.7%, 2911/3283) and of a minority ethnicity (72.2%, 2371/3283), with most participants being farmers and outdoor government workers (90.2%, 2960/3283). Using a small volume of blood (≈ 10 µL) the PCR assay revealed that 1.74% (57/3283) of the participants had asymptomatic malaria (P. falciparum 1.07%, P. vivax 0.40%, Plasmodium malariae 0.15% and mixed infections 0.12%). In contrast, the annual malaria prevalence rates for clinical malaria in the communities where the participants lived were 0.12% (108/90,395) in 2016 and 0.22% (201/93,184) in 2017. Seropositivity for at least one P. falciparum or one P. vivax antigen was 38.5% (1257/3262) and 31.1% (1022/3282), respectively. Age-dependent trends in the proportion of seropositive individuals in five of the districts discriminated the three districts with sustained low malaria prevalence from the two districts with higher transmission. CONCLUSIONS: Asymptomatic Plasmodium carriers were found to be substantially more prevalent than clinical cases in seven districts of Gia Lai province, and a third of the population had serological evidence of previous malaria exposure. The findings add knowledge on the extent of asymptomatic malaria and transmission for developing malaria elimination strategies for Vietnam.
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Malaria Falciparum , Malaria Vivax , Malaria , Adulto , Infecciones Asintomáticas/epidemiología , Estudios Transversales , Humanos , Malaria/epidemiología , Malaria Falciparum/epidemiología , Malaria Vivax/epidemiología , Masculino , Plasmodium falciparum , Plasmodium vivax , Prevalencia , Estudios Seroepidemiológicos , Vietnam/epidemiologíaRESUMEN
BACKGROUND: A global pandemic has been declared for coronavirus disease 2019 (COVID-19), which has serious impacts on human health and healthcare systems in the affected areas, including Vietnam. None of the previous studies have a framework to provide summary statistics of the virus variants and assess the severity associated with virus proteins and host cells in COVID-19 patients in Vietnam. METHOD: In this paper, we comprehensively investigated SARS-CoV-2 variants and immune responses in COVID-19 patients. We provided summary statistics of target sequences of SARS-CoV-2 in Vietnam and other countries for data scientists to use in downstream analysis for therapeutic targets. For host cells, we proposed a predictive model of the severity of COVID-19 based on public datasets of hospitalization status in Vietnam, incorporating a polygenic risk score. This score uses immunogenic SNP biomarkers as indicators of COVID-19 severity. RESULT: We identified that the Delta variant of SARS-CoV-2 is most prevalent in southern areas of Vietnam and it is different from other areas in the world using various data sources. Our predictive models of COVID-19 severity had high accuracy (Random Forest AUC = 0.81, Elastic Net AUC = 0.7, and SVM AUC = 0.69) and showed that the use of polygenic risk scores increased the models' predictive capabilities. CONCLUSION: We provided a comprehensive analysis for COVID-19 severity in Vietnam. This investigation is not only helpful for COVID-19 treatment in therapeutic target studies, but also could influence further research on the disease progression and personalized clinical outcomes.
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Tratamiento Farmacológico de COVID-19 , COVID-19 , Infecciones por Coronavirus , Neumonía Viral , Betacoronavirus , COVID-19/epidemiología , Estudio de Asociación del Genoma Completo , Humanos , SARS-CoV-2/genética , Vietnam/epidemiologíaRESUMEN
BACKGROUND: The composition of the digestive microbiota may be associated with outcome and infections in patients admitted to the intensive care unit (ICU). The dominance by opportunistic pathogens (such as Enterococcus) has been associated with death. However, whether this association remains all throughout the hospitalization are lacking. METHODS: We performed a single-center observational prospective cohort study in critically ill patients admitted with severe SARS-CoV-2 infection. Oropharyngeal and rectal swabs were collected at admission and then twice weekly until discharge or death. Quantitative cultures for opportunistic pathogens were performed on oropharyngeal and rectal swabs. The composition of the intestinal microbiota was assessed by 16S rDNA sequencing. Oropharyngeal and intestinal concentrations of opportunistic pathogens, intestinal richness and diversity were entered into a multivariable Cox model as time-dependent covariates. The primary outcome was death at day 90. RESULTS: From March to September 2020, 95 patients (765 samples) were included. The Simplified Acute Physiology Score 2 (SAPS 2) at admission was 33 [24; 50] and a Sequential Organ Failure Assessment score (SOFA score) at 6 [4; 8]. Day 90 all-cause mortality was 44.2% (42/95). We observed that the oropharyngeal and rectal concentrations of Enterococcus spp., Staphylococcus aureus and Candida spp. were associated with a higher risk of death. This association remained significant after adjustment for prognostic covariates (age, chronic disease, daily antimicrobial agent use and daily SOFA score). A one-log increase in Enterococcus spp., S. aureus and Candida spp. in oropharyngeal or rectal swabs was associated with a 17% or greater increase in the risk of death. CONCLUSION: We found that elevated oropharyngeal/intestinal Enterococcus spp. S. aureus and Candida spp. concentrations, assessed by culture, are associated with mortality, independent of age, organ failure, and antibiotic therapy, opening prospects for simple and inexpensive microbiota-based markers for the prognosis of critically ill SARS-CoV-2 patients.
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COVID-19 , SARS-CoV-2 , Adulto , Antibacterianos , Candida , Enfermedad Crítica , ADN Ribosómico , Humanos , Unidades de Cuidados Intensivos , Estudios Prospectivos , Staphylococcus aureusRESUMEN
Azole-resistant environmental Aspergillus fumigatus presents a threat to public health but the extent of this threat in Southeast Asia is poorly described. We conducted environmental surveillance in the Mekong Delta region of Vietnam, collecting air and ground samples across key land-use types, and determined antifungal susceptibilities of Aspergillus section Fumigati (ASF) isolates and azole concentrations in soils. Of 119 ASF isolates, 55% were resistant (or non-wild type) to itraconazole, 65% to posaconazole and 50% to voriconazole. Azole resistance was more frequent in A. fumigatus sensu stricto isolates (95%) than other ASF species (32%). Resistant isolates and agricultural azole residues were overrepresented in samples from cultivated land. cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus sensu stricto isolates carried known resistance mutations, with TR34 /L98H most frequent (34/38).
Asunto(s)
Aspergillus fumigatus , Azoles , Antifúngicos/farmacología , Azoles/farmacología , Farmacorresistencia Fúngica/genética , Proteínas Fúngicas/genética , Pruebas de Sensibilidad Microbiana , VietnamRESUMEN
The increasing incidence of carbapenemase-producing Gram-negative bacilli (C-PGNB) represents a major public health challenge. Rapid detection of digestive colonization with C-PGNB is fundamental to control their spread. We performed the validation of a rapid protocol for C-PGNB detection directly on rectal swabs. We developed a protocol combining enrichment by a rapid selective subculture of the rectal swab medium and realization of a Resist-4 O.K.N.V. K-SeT test on the bacterial pellet obtained. The limit of detection and performances of this protocol were validated in vitro on 52 C-PGNB strains spiked on a calibrated sample suspension and confirmed in clinical settings on 144 rectal swabs sampled from patients with C-PGNB digestive colonization (n = 48) and controls (patients with extended-spectrum beta-lactamase [ESBL] colonization [n = 48] and without carbapenemase/ESBL [n = 48]). The protocol detected, with 100% sensitivity, the presence of the 15 OXA-48-, 14 KPC-, 13 NDM-, and 10 VIM-producing GNB from 103 CFU/ml. The limit of detection was 2 × 102 CFU/ml. Among the 48 C-PGNB-containing rectal swabs of the validation cohort, 46 were accurately detected. False negative were observed for 1 NDM-producing Acinetobacter baumannii strain and 1 OXA-48-producing Escherichia coli strain. The 96 control swabs were negative. Sensitivity and specificity for C-PGNB detection were 97.7% (95% confidence interval [CI], 87.7 to 100) and 100% (95% CI, 96.2 to 100). The negative likelihood ratio was 0.04 (95% CI, 0.01 to 0.16). Considering a C-PGNB digestive colonization prevalence between 0.01% and 0.1%, positive and negative predictive values were 100%. Our protocol is a rapid and low-cost method detecting accurately the digestive colonization with carbapenemase-producing Enterobacteriaceae in 4 h without any requirement for specific equipment.