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1.
J Neurovirol ; 29(6): 706-712, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37902948

RESUMEN

The significance of Epstein-Barr virus (EBV) detection in the cerebrospinal spinal fluid (CSF) in people living with HIV (PLWH) is not entirely understood. The detection of EBV DNA may represent active central nervous system (CNS) infection, reactivation in the setting of another CNS pathogen or due to impaired immunity, or detection of quiescent virus. We screened 470 adult PLWH in Zambia with neurological symptoms for the presence of EBV DNA in the CSF. We performed quantitative EBV PCR on the CSF and blood. We then performed quantitative EBV DNA PCR on the blood of controls with documented HIV viral suppression without CNS symptoms. The prevalence of EBV DNA in the CSF of patients with CNS symptoms was 28.9% (136/470). EBV DNA positivity was associated with younger age, shorter duration of HIV diagnosis, lower CSF glucose levels, higher CSF protein and white blood cell levels, and a positive CSF Mycobacterium tuberculosis result. The median EBV DNA load was 8000 cps/mL in both the CSF and blood with a range of 2000-2,753,000 cps/mL in the CSF and 1000 to 1,871,000 cps/mL in the blood. Molecular screening of CSF for other possible causes of infection identified Mycobacterium tuberculosis in 30.1% and cytomegalovirus (CMV) in 10.5% of samples. EBV DNA load in the blood and CSF was not associated with mortality. Our results suggest that even though EBV DNA was commonly detected in the CSF of our population, it appears to have limited clinical significance regardless of EBV DNA load.


Asunto(s)
Infecciones del Sistema Nervioso Central , Infecciones por Virus de Epstein-Barr , Infecciones por VIH , Adulto , Humanos , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Herpesvirus Humano 4/genética , Zambia/epidemiología , ADN Viral , Infecciones del Sistema Nervioso Central/complicaciones , Sistema Nervioso Central , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico
2.
Chemistry ; 29(7): e202202881, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36351205

RESUMEN

Photodynamic therapy (PDT) is currently limited by the inability of photosensitizers (PSs) to enter cancer cells and generate sufficient reactive oxygen species. Utilizing phosphorescent triplet states of novel PSs to generate singlet oxygen offers exciting possibilities for PDT. Here, we report phosphorescent octahedral molybdenum (Mo)-based nanoclusters (NC) with tunable toxicity for PDT of cancer cells without use of rare or toxic elements. Upon irradiation with blue light, these molecules are excited to their singlet state and then undergo intersystem crossing to their triplet state. These NCs display surprising tunability between their cellular cytotoxicity and phototoxicity by modulating the apical halide ligand with a series of short chain fatty acids from trifluoroacetate to heptafluorobutyrate. The NCs are effective in PDT against breast, skin, pancreas, and colon cancer cells as well as their highly metastatic derivatives, demonstrating the robustness of these NCs in treating a wide variety of aggressive cancer cells. Furthermore, these NCs are internalized by cancer cells, remain in the lysosome, and can be modulated by the apical ligand to produce singlet oxygen. Thus, (Mo)-based nanoclusters are an excellent platform for optimizing PSs. Our results highlight the profound impact of molecular nanocluster chemistry in PDT applications.


Asunto(s)
Compuestos Inorgánicos , Fotoquimioterapia , Fotoquimioterapia/métodos , Oxígeno Singlete/química , Ligandos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/química , Especies Reactivas de Oxígeno/química , Molibdeno
3.
World J Surg ; 46(7): 1669-1677, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35397678

RESUMEN

BACKGROUND: The normal healing of surgical wounds can be disrupted by infection and/or dehiscence, leading to development of chronic, non-healing wounds (NHW). Diagnosis of NHWs is via clinical acumen and analysis of microbiology wound swabs. Volatile organic compounds (VOCs) are emitted generally by human subjects and specifically as products of bacterial metabolism and are detected in the wound area. This systematic review will assess the potential use of VOCs released by surgical wounds as a non-invasive method for identifying bacterial species and the progression to NHW. METHOD: A systematic search of studies, via PRISMA guidelines, was conducted. Of 220 papers screened, seven studies were included. Outcome data were extracted on methods for VOC analysis and wound/bacterial VOC profiles. RESULTS: The studies have shown that VOC profiles are identified by two methods: gas chromatography-mass spectrometry and electronic nose. There are VOC profiles associated with causative bacterial species, with early indications that they could be anatomically specific or could monitor treatment effects. CONCLUSION: VOC profiling of bacterial species within wounds is possible and could become a point of care test. More research is needed on specific VOC profiles to wound location and whether these profiles may predict progression to NHW.


Asunto(s)
Herida Quirúrgica , Compuestos Orgánicos Volátiles , Bacterias , Diagnóstico Precoz , Humanos , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/metabolismo
4.
Emerg Infect Dis ; 26(4): 811-814, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32187004

RESUMEN

We detected West Nile virus (WNV) nucleic acid in crocodiles (Crocodylus niloticus) in Zambia. Phylogenetically, the virus belonged to lineage 1a, which is predominant in the Northern Hemisphere. These data provide evidence that WNV is circulating in crocodiles in Africa and increases the risk for animal and human transmission.


Asunto(s)
Caimanes y Cocodrilos , Fiebre del Nilo Occidental , Virus del Nilo Occidental , Animales , Humanos , Fiebre del Nilo Occidental/epidemiología , Fiebre del Nilo Occidental/veterinaria , Virus del Nilo Occidental/genética , Zambia/epidemiología
5.
Clin Infect Dis ; 69(8): 1360-1367, 2019 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-30596901

RESUMEN

BACKGROUND: Sepsis is a leading cause of neonatal mortality in low-resource settings. As facility-based births become more common, the proportion of neonatal deaths due to hospital-onset sepsis has increased. METHODS: We conducted a prospective cohort study in a neonatal intensive care unit in Zambia where we implemented a multifaceted infection prevention and control (IPC) bundle consisting of IPC training, text message reminders, alcohol hand rub, enhanced environmental cleaning, and weekly bathing of babies ≥1.5 kg with 2% chlorhexidine gluconate. Hospital-associated sepsis, bloodstream infection (BSI), and mortality (>3 days after admission) outcome data were collected for 6 months prior to and 11 months after bundle implementation. RESULTS: Most enrolled neonates had a birth weight ≥1.5 kg (2131/2669 [79.8%]). Hospital-associated mortality was lower during the intervention than baseline period (18.0% vs 23.6%, respectively). Total mortality was lower in the intervention than prior periods. Half of enrolled neonates (50.4%) had suspected sepsis; 40.8% of cultures were positive. Most positive blood cultures yielded a pathogen (409/549 [74.5%]), predominantly Klebsiella pneumoniae (289/409 [70.1%]). The monthly rate and incidence density rate of suspected sepsis were lower in the intervention period for all birth weight categories, except babies weighing <1.0 kg. The rate of BSI with pathogen was also lower in the intervention than baseline period. CONCLUSIONS: A simple IPC bundle can reduce sepsis and death in neonates hospitalized in high-risk, low-resource settings. Further research is needed to validate these findings in similar settings and to identify optimal implementation strategies for improvement and sustainability. CLINICAL TRIALS REGISTRATION: NCT02386592.


Asunto(s)
Antiinfecciosos Locales/administración & dosificación , Bacteriemia/prevención & control , Clorhexidina/análogos & derivados , Control de Infecciones , Sepsis/prevención & control , Bacteriemia/epidemiología , Bacteriemia/microbiología , Peso al Nacer , Clorhexidina/administración & dosificación , Estudios de Cohortes , Mortalidad Hospitalaria , Hospitales , Humanos , Lactante , Mortalidad Infantil , Recién Nacido , Control de Infecciones/métodos , Unidades de Cuidado Intensivo Neonatal , Muerte Perinatal/prevención & control , Estudios Prospectivos , Sepsis/epidemiología , Sepsis/microbiología , Sepsis/mortalidad , Zambia/epidemiología
6.
Int J Sports Med ; 40(2): 125-132, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30605923

RESUMEN

The present study evaluated reproducibility of the inert gas rebreathing method to estimate cardiac output at rest and during cardiopulmonary exercise testing. Thirteen healthy subjects (10 males, 3 females, ages 23-32 years) performed maximal graded cardiopulmonary exercise stress test using a cycle ergometer on 2 occasions (Test 1 and Test 2). Participants cycled at 30-watts/3-min increments until peak exercise. Hemodynamic variables were assessed at rest and during different exercise intensities (i. e., 60, 120, 150, 180 watts) using an inert gas rebreathing technique. Cardiac output and stroke volume were not significantly different between the 2 tests at rest 7.4 (1.6) vs. 7.1 (1.2) liters min-1, p=0.54; 114 (28) vs. 108 (15) ml beat-1, p=0.63) and all stages of exercise. There was a significant positive relationship between Test 1 and Test 2 cardiac outputs when data obtained at rest and during exercise were combined (r=0.95, p<0.01 with coefficient of variation of 6.0%), at rest (r=0.90, p<0.01 with coefficient of variation of 5.1%), and during exercise (r=0.89, p<0.01 with coefficient of variation 3.3%). The mean difference and upper and lower limits of agreement between repeated measures of cardiac output at rest and peak exercise were 0.4 (-1.1 to 1.8) liter min-1 and 0.5 (-2.3 to 3.3) liter min-1, respectively. The inert gas rebreathing method demonstrates an acceptable level of test-retest reproducibility for estimating cardiac output at rest and during cardiopulmonary exercise testing at higher metabolic demands.


Asunto(s)
Gasto Cardíaco , Prueba de Esfuerzo , Adulto , Pruebas Respiratorias , Femenino , Humanos , Masculino , Gases Nobles , Intercambio Gaseoso Pulmonar , Reproducibilidad de los Resultados , Descanso , Volumen Sistólico , Adulto Joven
7.
Indian Pacing Electrophysiol J ; 19(3): 84-89, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30914382

RESUMEN

BACKGROUND: Catheter-tissue contact force is an important factor influencing lesion size and efficacy and thereby potential for arrhythmia recurrence following accessory pathway (AP) radiofrequency ablation. We aim to evaluate adequacy and perception of catheter contact on the tricuspid and mitral annuli. METHODS: Data were collected from 42 patients undergoing catheter ablation. Operators were blinded to contact force information and reported perceived contact (poor, moderate, or good) while positioning the catheter at four tricuspid annular sites (12, 9, 6 and 4 o'clock positions; abbreviated as TA12, TA9, TA6 and TA4) and three mitral annular sites (3, 5 and 7 o'clock positions; abbreviated as MA3, MA5 and MA7) through long vascular sheaths. RESULTS: The highest and lowest mean contact forces were obtained at MA7 (13.3 ±â€¯1.7 g) and TA12 (3.6 g ±â€¯1.3 g) respectively. Mean contact force on tricuspid annulus (6.1 g ±â€¯0.9 g) was lower than mitral annulus (9.8 ±â€¯0.9 g) locations (p = 0.0036), with greater proportion of sites with <10 g contact force (81.7% vs 60.4%; p = 0.0075). Perceived contact had no impact on measured mean contact force for both mitral and tricuspid annular positions (p = 0.959 and 0.671 respectively). There was correlation of both impedance and atrial electrogram amplitude with contact force, though insufficient to be clinically applicable. CONCLUSION: A high proportion of annular catheter applications have low contact force despite being performed with long vascular sheaths in the hands of experienced operators. In addition, there was no impact of operator perceived contact force on actual measured contact force. This may carry implications for success of AP ablation.

8.
J Med Virol ; 90(11): 1757-1764, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30011348

RESUMEN

BACKGROUND: Human herpesvirus 6B (HHV-6B) is the causative agent of Roseola infantum, and has also been suggested to play a role in the pathogenesis of febrile seizures in young children, a percentage of whom go on to develop febrile status epilepticus (FSE), but the existing data is conflicting and inconclusive. HHV-6A is a distinct species, rarely detected in most parts of the world, but prior studies suggest a higher prevalence in febrile African children. We describe a case-control study comparing the frequency of HHV-6A and/or HHV-6B infections in children with febrile seizures (including FSE) and a control group of febrile children without seizures. METHODS: We recruited children aged 6 to 60 months admitted with a febrile illness with (cases) or without (controls) seizures presenting within 48 hours of commencement of fever. Three milliliters of whole blood was centrifuged and plasma stored at -80°C for pooled screening for HHV-6B and HHV-6A by Taqman real-time polymerase chain reaction. RESULTS: 102 cases and 95 controls were recruited. The prevalence of HHV-6B DNA detection did not differ significantly between cases (5.8% (6/102)) and controls (10.5% (10/95)) but HHV-6B infection was associated with FSE (OR, 15; 95% CI, [1.99-120]; P= 0.009). HHV-6A was not detected. CONCLUSION: Prevalence of HHV-6B was similar among cases and controls. Within the FS group, HHV-6B infection was associated with FSE, suggesting HHV-6B infections could play a role in the pathogenesis of FSE.


Asunto(s)
Exantema Súbito/complicaciones , Exantema Súbito/patología , Herpesvirus Humano 6/aislamiento & purificación , Convulsiones Febriles/epidemiología , Estado Epiléptico/epidemiología , Estudios de Casos y Controles , Preescolar , Exantema Súbito/virología , Femenino , Herpesvirus Humano 6/genética , Hospitales , Humanos , Lactante , Masculino , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Zambia/epidemiología
9.
Infection ; 45(6): 831-839, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28779436

RESUMEN

PURPOSE: The purpose of this study was to establish a baseline for measuring the impact of the programmatic management of drug-resistant TB program by following up on outcomes of all patients diagnosed with multidrug-resistant tuberculosis in Zambia between 2012 and 2014. METHODS: A cohort study of all the MDR-TB patients diagnosed at the national TB reference laboratory from across Zambia. MDR-TB was diagnosed by culture and DST, whereas outcome data were collected in 2015 by patient record checks and home visits. RESULTS: The total number of patients diagnosed was 258. Of those, 110 (42.6%) patients were traceable for this study. There were 67 survivor participants (60.9%); 43 (39.1%) were deceased. Out of the 110 patients who were traced, only 71 (64.5%) were started on second-line treatment. Twenty-nine (40.8%) patients were declared cured and 16.9% were still on treatment; 8.4% had failed treatment. The survival rate was 20.2 per 100 person-years of follow-up. Taking ARVs was associated with a decreased risk of dying (hazard ratio 0.12, p = 0.002). Sex, age, marital status and treatment category were not important predictors of survival in MDR-TB patients. CONCLUSIONS: More than half of the patients diagnosed with MDR-TB were lost to follow-up before second-line treatment was initiated.


Asunto(s)
Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Mycobacterium tuberculosis/fisiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Insuficiencia del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/mortalidad , Adulto Joven , Zambia/epidemiología
10.
Rev Med Virol ; 26(6): 446-454, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27593704

RESUMEN

Lujo virus is a novel Old World arenavirus identified in Southern Africa in 2008 as the cause of a viral hemorrhagic fever (VHF) characterized by nosocomial transmission with a high case fatality rate of 80% (4/5 cases). Whereas this outbreak was limited, the unprecedented Ebola virus disease outbreak in West Africa, and recent Zika virus disease epidemic in the Americas, has brought into acute focus the need for preparedness to respond to rare but potentially highly pathogenic outbreaks of zoonotic or arthropod-borne viral infections. A key determinant for effective control of a VHF outbreak is the time between primary infection and diagnosis of the index case. Here, we review the Lujo VHF outbreak of 2008 and discuss how preparatory measures with respect to developing diagnostic capacity might be effectively embedded into existing national disease control networks, such as those for human immunodeficiency virus, tuberculosis, and malaria.


Asunto(s)
Infecciones por Arenaviridae/epidemiología , Defensa Civil , Brotes de Enfermedades , Fiebres Hemorrágicas Virales/epidemiología , Lujo virus/aislamiento & purificación , África Austral/epidemiología , Infecciones por Arenaviridae/transmisión , Infecciones por Arenaviridae/virología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/transmisión , Infección Hospitalaria/virología , Transmisión de Enfermedad Infecciosa/prevención & control , Fiebres Hemorrágicas Virales/transmisión , Fiebres Hemorrágicas Virales/virología , Humanos , Control de Infecciones/métodos
11.
BMC Med ; 14: 99, 2016 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-27363601

RESUMEN

BACKGROUND: Autopsy studies are the gold standard for determining cause-of-death and can inform on improved diagnostic strategies and algorithms to improve patient care. We conducted a cross-sectional observational autopsy study to describe the burden of respiratory tract infections in inpatient children who died at the University Teaching Hospital in Lusaka, Zambia. METHODS: Gross pathology was recorded and lung tissue was analysed by histopathology and molecular diagnostics. Recruitment bias was estimated by comparing recruited and non-recruited cases. RESULTS: Of 121 children autopsied, 64 % were male, median age was 19 months (IQR, 12-45 months). HIV status was available for 97 children, of whom 34 % were HIV infected. Lung pathology was observed in 92 % of cases. Bacterial bronchopneumonia was the most common pathology (50 %) undiagnosed ante-mortem in 69 % of cases. Other pathologies included interstitial pneumonitis (17 %), tuberculosis (TB; 8 %), cytomegalovirus pneumonia (7 %) and pneumocystis Jirovecii pneumonia (5 %). Comorbidity between lung pathology and other communicable and non-communicable diseases was observed in 80 % of cases. Lung tissue from 70 % of TB cases was positive for Mycobacterium tuberculosis by molecular diagnostic tests. A total of 80 % of TB cases were comorbid with malnutrition and only 10 % of TB cases were on anti-TB therapy when they died. CONCLUSIONS: More proactive testing for bacterial pneumonia and TB in paediatric inpatient settings is needed.


Asunto(s)
Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/microbiología , Autopsia , Niño , Trastornos de la Nutrición del Niño/epidemiología , Preescolar , Comorbilidad , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Zambia/epidemiología
12.
Environ Sci Technol ; 50(1): 349-58, 2016 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-26580228

RESUMEN

Emerging technologies present significant challenges to researchers, decision-makers, industry professionals, and other stakeholder groups due to the lack of quantitative risk, benefit, and cost data associated with their use. Multi-criteria decision analysis (MCDA) can support early decisions for emerging technologies when data is too sparse or uncertain for traditional risk assessment. It does this by integrating expert judgment with available quantitative and qualitative inputs across multiple criteria to provide relative technology scores. Here, an MCDA framework provides preliminary insights on the suitability of emerging technologies for environmental remediation by comparing nanotechnology and synthetic biology to conventional remediation methods. Subject matter experts provided judgments regarding the importance of criteria used in the evaluations and scored the technologies with respect to those criteria. The results indicate that synthetic biology may be preferred over nanotechnology and conventional methods for high expected benefits and low deployment costs but that conventional technology may be preferred over emerging technologies for reduced risks and development costs. In the absence of field data regarding the risks, benefits, and costs of emerging technologies, structuring evidence-based expert judgment through a weighted hierarchy of topical questions may be helpful to inform preliminary risk governance and guide emerging technology development and policy.


Asunto(s)
Restauración y Remediación Ambiental , Técnicas de Apoyo para la Decisión , Restauración y Remediación Ambiental/economía , Restauración y Remediación Ambiental/métodos , Restauración y Remediación Ambiental/tendencias , Medición de Riesgo
13.
Heart Lung Circ ; 25(11): e152-e154, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27523463

RESUMEN

Deglutition-induced atrial tachycardia is a rare arrhythmia with a poor response to medical therapy. Electrophysiological study is challenging due to the dependence of induction on swallowing. We present a novel approach to management of deglutition-induced atrial tachycardia arising from right superior pulmonary vein. Use of minimal conscious sedation and repeated swallow challenge inductions, together with contact force-guided mapping were key determinants of success. We review published cases, discussing potential mechanisms including oesophageal distension and neural reflexes.


Asunto(s)
Deglución , Técnicas Electrofisiológicas Cardíacas , Taquicardia/fisiopatología , Taquicardia/terapia , Anciano , Humanos , Masculino
14.
Clin Infect Dis ; 60(3): 423-31, 2015 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-25352585

RESUMEN

BACKGROUND: Betaherpesviruses are established causes of morbidity and mortality in immunosuppressed patient groups but have been little studied in sub-Saharan Africa, the epicenter of the human immunodeficiency virus (HIV) pandemic. In this region, primary infections with human cytomegalovirus (HCMV) and human herpesvirus type 6 (HHV-6) type 6 are endemic in infancy, but the clinical impact of these infections among pediatric inpatient groups is poorly characterized and assumptive, based largely on data from Western populations. METHODS: We used TaqMan polymerase chain reaction to screen sera from a group of 303 pediatric inpatients aged between 3 weeks and 2 years, at the University Teaching Hospital in Lusaka, Zambia. We report the prevalence of DNAemia and viral loads within this patient group, and evaluate possible clinical associations/risk factors for betaherpesvirus infections in these hospitalized children. RESULTS: We detected betaherpesvirus DNAemia in 59.1% (179/303) of children. HCMV was the most prevalent (41.3%), followed by HHV-6B (20.5%), HHV-7 (20.1%), and HHV-6A (0.3%). HIV infection (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.37-3.90; P = .002), being underweight (OR, 1.82; 95% CI, 1.06-3.12; P = .03), and an admission diagnosis of suspected meningitis (OR, 5.72; 95% CI, 1.07-30.5; P = .041) were independently associated with an increased odds of HCMV DNAemia. Conversely, HHV-6B and HHV-7 DNAemia were not associated with HIV, underweight, or admission diagnosis. Median HCMV viral load was moderately but significantly higher in HIV-infected children. CONCLUSIONS: Highly prevalent HCMV DNAemia was independently associated with HIV infection and being underweight across all age groups, and was also associated with meningitis, with previously underappreciated implications for the health and development of African children.


Asunto(s)
Infecciones por Citomegalovirus/epidemiología , Citomegalovirus/aislamiento & purificación , Herpesvirus Humano 6/aislamiento & purificación , Herpesvirus Humano 7/aislamiento & purificación , Infecciones por Roseolovirus/epidemiología , Preescolar , Citomegalovirus/genética , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/virología , ADN Viral/sangre , Femenino , Infecciones por VIH/complicaciones , Herpesvirus Humano 6/genética , Herpesvirus Humano 7/genética , Hospitales de Enseñanza , Hospitales Universitarios , Humanos , Huésped Inmunocomprometido , Lactante , Recién Nacido , Masculino , Prevalencia , Derivación y Consulta , Factores de Riesgo , Infecciones por Roseolovirus/etiología , Infecciones por Roseolovirus/virología , Delgadez , Carga Viral , Zambia
15.
Clin Infect Dis ; 61Suppl 3: S102-18, 2015 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-26409271

RESUMEN

Despite concerted efforts over the past 2 decades at developing new diagnostics, drugs, and vaccines with expanding pipelines, tuberculosis remains a global emergency. Several novel diagnostic technologies show promise of better point-of-care rapid tests for tuberculosis including nucleic acid-based amplification tests, imaging, and breath analysis of volatile organic compounds. Advances in new and repurposed drugs for use in multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis have focused on development of several new drug regimens and their evaluation in clinical trials and now influence World Health Organization guidelines. Since the failure of the MVA85A vaccine 2 years ago, there have been no new tuberculosis vaccine candidates entering clinical testing. The current status quo of the lengthy treatment duration and poor treatment outcomes associated with MDR/XDR tuberculosis and with comorbidity of tuberculosis with human immunodeficiency virus and noncommunicable diseases is unacceptable. New innovations and political and funder commitment for early rapid diagnosis, shortening duration of therapy, improving treatment outcomes, and prevention are urgently required.


Asunto(s)
Antituberculosos/uso terapéutico , Vacunas contra la Tuberculosis , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Antituberculosos/química , Antituberculosos/clasificación , Ensayos Clínicos como Asunto , Tuberculosis Extensivamente Resistente a Drogas/diagnóstico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/prevención & control , Infecciones por VIH/complicaciones , Humanos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Sistemas de Atención de Punto/economía , Tuberculosis/complicaciones , Tuberculosis/prevención & control , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/prevención & control , Vacunas de ADN , Organización Mundial de la Salud
16.
Eur Respir J ; 46(3): 761-70, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26113682

RESUMEN

We evaluated the diagnostic performance of two tests based on the release of lipoarabinomannan (LAM) into the urine, the MTB-LAM-ELISA assay and the Determine TB-LAM-strip assay, in children with suspected tuberculosis (TB) in a high TB/HIV-prevalence setting.In a prospective study, 132 children with suspected active TB were assigned to diagnostic subgroups. Urine samples were subjected to testing by both assays to ascertain sensitivity and specificity. Host factors associated with positive LAM results were investigated and LAM excretion monitored after antituberculous treatment initiation.18 (13.6%) children had culture-confirmed pulmonary TB. The assays' sensitivity was higher in HIV-positive versus HIV-negative children: 70% (95% confidence interval 35-93%) versus 13% (0-53%) for MTB-LAM-ELISA and 50% (19-81%) versus 0% (0-37%) for Determine TB-LAM. In 35 (27%) children with excluded active TB, both assays showed a specificity of 97.1% (85-100%). Proteinuria and low body mass index were independently associated with LAM positivity. In most patients, LAM excretion declined to zero during or at conclusion of antituberculous treatment.HIV/TB co-infected children might benefit from LAM-based tests to aid early TB diagnosis and subsequent positive impact on morbidity and mortality. Using LAM as a rule-in and treatment-monitoring tool may also show further potential.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/orina , Lipopolisacáridos/orina , Tuberculosis/epidemiología , Tuberculosis/orina , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Niño , Preescolar , Estudios de Cohortes , Países en Desarrollo , Enfermedades Endémicas , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Incidencia , Lipopolisacáridos/análisis , Masculino , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Esputo/microbiología , Tanzanía/epidemiología , Tuberculosis/diagnóstico , Urinálisis/métodos
17.
Clin Infect Dis ; 58(5): 728-35, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24265360

RESUMEN

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the major infectious cause of birth defects and hearing loss globally. There is a growing recognition of the potential clinical impact of congenital CMV infections in high-seroprevalence settings. METHODS: A cross-sectional study of neonatal admissions at a large referral center in sub-Saharan Africa to determine the prevalence of both symptomatic and asymptomatic congenital CMV infection was performed. Real-time polymerase chain reaction was used to screen DNA-extracted sera, urine, and saliva, and an enzyme-linked immunosorbent assay was used to screen serum samples for anti-CMV immunoglobulin M. Multivariate binary logistic regression was used to identify risk factors associated with increased odds of congenital CMV infection. RESULTS: Congenital CMV was detected in 3.8% (15/395) of neonates. Among these infants, 6 of 15 (40%) presented with jaundice, 1 of whom also had petechiae. Congenital CMV infection was detected in 9 of 79 (11.4%; 95% confidence interval [CI], 6.1%-20.3%) neonates born to human immunodeficiency virus (HIV)-infected mothers, and both maternal HIV (odds ratio [OR], 6.661 [95% CI, 2.126-20.876], P = .001) and jaundice (OR, 5.701 [95% CI, 1.776-18.306], P = .003) were independently linked with significantly increased odds of congenital CMV infection. CONCLUSIONS: Congenital and early infant CMV infections may have important consequences for child health in sub-Saharan Africa and other high HIV and CMV seroprevalence populations globally.


Asunto(s)
Infecciones por Citomegalovirus/congénito , Infecciones por Citomegalovirus/epidemiología , Infecciones por VIH/complicaciones , Hospitalización , Complicaciones Infecciosas del Embarazo/epidemiología , África del Sur del Sahara , Anticuerpos Antivirales/sangre , Estudios Transversales , ADN Viral/análisis , Ensayo de Inmunoadsorción Enzimática , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Inmunoglobulina M/sangre , Recién Nacido , Masculino , Embarazo , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Saliva/virología , Suero/virología , Centros de Atención Terciaria , Orina/virología
18.
Environ Sci Technol ; 48(19): 11543-50, 2014 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-25209330

RESUMEN

Assessing the best options among emerging technologies (e.g., new chemicals, nanotechnologies) is complicated because of trade-offs across benefits and risks that are difficult to quantify given limited and fragmented availability of information. This study demonstrates the integration of multicriteria decision analysis (MCDA) and life cycle assessment (LCA) to address technology alternative selection decisions. As a case study, prioritization of six lumber treatment alternatives [micronized copper quaternary (MCQ); alkaline copper quaternary (ACQ); water-borne copper naphthenate (CN); oil-borne copper naphthenate (CNo); water-borne copper quinolate (CQ); and water-borne zinc naphthenate (ZN)] for military use are considered. Multiattribute value theory (MAVT) is used to derive risk and benefit scores. Risk scores are calculated using a cradle-to-gate LCA. Benefit scores are calculated by scoring of cost, durability, and corrosiveness criteria. Three weighting schemes are used, representing Environmental, Military and Balanced stakeholder perspectives. Aggregated scores from all three perspectives show CQ to be the least favorable alterative. MCQ is identified as the most favorable alternative from the Environmental stakeholder perspective. From the Military stakeholder perspective, ZN is determined to be the most favorable alternative, followed closely by MCQ. This type of scoring and ranking of multiple heterogeneous criteria in a systematic and transparent way facilitates better justification of technology selection and regulation.


Asunto(s)
Técnicas de Apoyo para la Decisión , Medición de Riesgo/métodos , Algoritmos , Corrosión , Costos y Análisis de Costo , Ambiente , Combustibles Fósiles/análisis , Medición de Riesgo/economía , Estados Unidos , United States Environmental Protection Agency , Madera
19.
Environ Sci Technol ; 48(16): 9478-85, 2014 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-24957130

RESUMEN

Effective management of contaminated sediments is important for long-term human and environmental health, but site-management decisions are often made under high uncertainty and without the help of structured decision support tools. Potential trade-offs between remedial costs, environmental effects, human health risks, and societal benefits, as well as fundamental differences in stakeholder priorities, complicate decision making. Formal decision-analytic tools such as multicriteria decision analysis (MCDA) move beyond ad hoc decision support to quantitatively and holistically rank management alternatives and add transparency and replicability to the evaluation process. However, even the best decisions made under uncertainty may be found suboptimal in hindsight, once additional scientific, social, economic, or other details become known. Value of information (VoI) analysis extends MCDA by systematically evaluating the impact of uncertainty on a decision. VoI prioritizes future research in terms of expected decision relevance by helping decision makers estimate the likelihood that additional information will improve decision confidence or change their selection of a management plan. In this study, VoI analysis evaluates uncertainty, estimates decision confidence, and prioritizes research to inform selection of a sediment capping strategy for the dibenzo-p-dioxin and -furan contaminated Grenland fjord system in southern Norway. The VoI model extends stochastic MCDA to model decisions with and without simulated new information and compares decision confidence across scenarios with different degrees of remaining uncertainty. Results highlight opportunities for decision makers to benefit from additional information by anticipating the improved decision confidence (or lack thereof) expected from reducing uncertainties for each criterion or combination of criteria. This case study demonstrates the usefulness of VoI analysis for environmental decisions by predicting when decisions can be made confidently, for prioritizing areas of research to pursue to improve decision confidence, and for differentiating between decision-relevant and decision-irrelevant differences in evaluation perspectives, all of which help guide meaningful deliberation toward effective consensus solutions.


Asunto(s)
Toma de Decisiones , Sedimentos Geológicos , Contaminantes Químicos del Agua , Benzofuranos/análisis , Benzofuranos/toxicidad , Técnicas de Apoyo para la Decisión , Dioxinas/análisis , Dioxinas/toxicidad , Ambiente , Humanos , Difusión de la Información , Noruega , Probabilidad , Salud Pública , Procesos Estocásticos , Incertidumbre , Contaminación del Agua
20.
Environ Sci Technol ; 48(18): 10531-8, 2014 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-25121583

RESUMEN

Current research policy and strategy documents recommend applying life cycle assessment (LCA) early in research and development (R&D) to guide emerging technologies toward decreased environmental burden. However, existing LCA practices are ill-suited to support these recommendations. Barriers related to data availability, rapid technology change, and isolation of environmental from technical research inhibit application of LCA to developing technologies. Overcoming these challenges requires methodological advances that help identify environmental opportunities prior to large R&D investments. Such an anticipatory approach to LCA requires synthesis of social, environmental, and technical knowledge beyond the capabilities of current practices. This paper introduces a novel framework for anticipatory LCA that incorporates technology forecasting, risk research, social engagement, and comparative impact assessment, then applies this framework to photovoltaic (PV) technologies. These examples illustrate the potential for anticipatory LCA to prioritize research questions and help guide environmentally responsible innovation of emerging technologies.


Asunto(s)
Conservación de los Recursos Naturales/métodos , Contaminación Ambiental/prevención & control , Materiales Manufacturados , Modelos Teóricos , Tecnología/normas , Conservación de los Recursos Naturales/estadística & datos numéricos , Conservación de los Recursos Naturales/tendencias , Contaminación Ambiental/estadística & datos numéricos , Humanos , Formulación de Políticas , Riesgo , Tecnología/estadística & datos numéricos , Tecnología/tendencias
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