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1.
J Mol Cell Cardiol ; 140: 42-55, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32105665

RESUMEN

The Drosophila heart provides a simple model to examine the remodelling of muscle insertions with growth, extracellular matrix (ECM) turnover, and fibrosis. Between hatching and pupation, the Drosophila heart increases in length five-fold. If major cardiac ECM components are secreted remotely, how is ECM "self assembly" regulated? We explored whether ECM proteases were required to maintain the morphology of a growing heart while the cardiac ECM expanded. An increase in expression of Drosophila's single tissue inhibitor of metalloproteinase (TIMP), or reduced function of metalloproteinase MMP2, resulted in fibrosis and ectopic deposition of two ECM Collagens; type-IV and fibrillar Pericardin. Significant accumulations of Collagen-IV (Viking) developed on the pericardium and in the lumen of the heart. Congenital defects in Pericardin deposition misdirected further assembly in the larva. Reduced metalloproteinase activity during growth also increased Pericardin fibre accumulation in ECM suspending the heart. Although MMP2 expression was required to remodel and position cardiomyocyte cell junctions, reduced MMP function did not impair expansion of the heart. A previous study revealed that MMP2 negatively regulates the size of the luminal cell surface in the embryonic heart. Cardiomyocytes align at the midline, but do not adhere to enclose a heart lumen in MMP2 mutant embryos. Nevertheless, these embryos hatch and produce viable larvae with bifurcated hearts, indicating a secondary pathway to lumen formation between ipsilateral cardiomyocytes. MMP-mediated remodelling of the ECM is required for organogenesis, and to prevent assembly of excess or ectopic ECM protein during growth. MMPs are not essential for normal growth of the Drosophila heart.


Asunto(s)
Drosophila melanogaster/crecimiento & desarrollo , Matriz Extracelular/metabolismo , Corazón/crecimiento & desarrollo , Larva/metabolismo , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Miocardio/metabolismo , Animales , Animales Modificados Genéticamente , Colágeno Tipo IV/metabolismo , Proteínas de Drosophila/metabolismo , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/genética , Organogénesis/genética , Inhibidores Tisulares de Metaloproteinasas/genética , Inhibidores Tisulares de Metaloproteinasas/metabolismo
2.
Epidemiol Infect ; 147: e233, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-31364572

RESUMEN

We conducted probabilistic data linkage of three population datasets for the Northern Territory (NT), Australia, to describe the incidence of preterm births, stillbirths, low birthweight and small for gestational age (SGA) per 1000 NT births; and influenza and pertussis hospitalisations per 1 00 000 NT births in infants <7 months of age, in a pre-maternal vaccination era. The Perinatal Trends dataset (1994-2014) formed the cohort of 78 382 births. Aboriginal mother-infant pairs (37%) had disproportionately higher average annual rates (AR) for all adverse birth outcomes compared to their non-Aboriginal counterparts; rate ratios: preterm births 2.2 (AR 142.4 vs. 64.7); stillbirths 2.3 (AR 10.8 vs. 4.6); low birthweight 2.9 (AR 54 vs. 19); and SGA 1.7 (AR 187 vs. 111). Hospitalisation (2000-2015) and Immunisation Register datasets (1994-2015), showed that influenza hospitalisations (n = 53) and rates were 42.3 times higher in Aboriginal infants (AR 254 vs. 6); and that pertussis hospitalisations (n = 37) were 7.1 times higher in Aboriginal infants (AR 142.5 vs. 20.2) compared to non-Aboriginal infants. These baseline data are essential to assess the safety and effectiveness of influenza and pertussis vaccinations in pregnant women from the NT. Remote living Aboriginal women and infants stand to benefit the most from these vaccines.


Asunto(s)
Control de Enfermedades Transmisibles , Hospitalización/estadística & datos numéricos , Gripe Humana/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Vacunación/estadística & datos numéricos , Tos Ferina/prevención & control , Adulto , Australia , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/epidemiología , Almacenamiento y Recuperación de la Información , Masculino , Northern Territory , Vacuna contra la Tos Ferina/administración & dosificación , Embarazo , Nacimiento Prematuro , Estudios Retrospectivos , Tos Ferina/epidemiología
3.
Math Biosci ; 309: 163-173, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30149021

RESUMEN

Infections with Sarcoptes scabiei, or scabies, remain common in many disadvantaged populations. Mass drug administration (MDA) has been used in such settings to achieve a rapid reduction in infection and transmission, with the goal of eliminating the public health burden of scabies. While prevalence has been observed to fall substantially following such an intervention, in some instances resurgence of infection to baseline levels has occurred over several years. To explore the biology underpinning this phenomenon, we have developed a theoretical model of scabies life-cycle and transmission dynamics in a homogeneously mixing population, and simulate the impact of mass drug treatment strategies acting on egg and mite life cycle stages (ovicidal) or mites alone (non-ovicidal). In order to investigate the dynamics of the system, we first define and calculate the optimal interval between treatment doses. We calculate the probability of eradication as a function of the number of optimally-timed successive treatment doses and the number of years over which a program is run. For the non-ovicidal intervention, we first show that at least two optimally-timed doses are required to achieve eradication. We then demonstrate that while more doses over a small number of years provides the highest chance of eradication, a similar outcome can be achieved with fewer doses delivered annually over a longer period of time. For the ovicidal intervention, we find that doses should be delivered as close together as possible. This work provides a platform for further research into optimal treatment strategies which may incorporate heterogeneity of transmission, and the interplay between MDA and enhancement of continuing scabies surveillance and treatment strategies.


Asunto(s)
Antiparasitarios/administración & dosificación , Modelos Biológicos , Sarcoptes scabiei , Escabiosis , Animales , Humanos , Sarcoptes scabiei/efectos de los fármacos , Sarcoptes scabiei/patogenicidad , Escabiosis/tratamiento farmacológico , Escabiosis/prevención & control , Escabiosis/transmisión
4.
Epidemiol Infect ; 146(9): 1194-1201, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29734959

RESUMEN

Prevalence of skin sores and scabies in remote Australian Aboriginal communities remains unacceptably high, with Group A Streptococcus (GAS) the dominant pathogen. We aim to better understand the drivers of GAS transmission using mathematical models. To estimate the force of infection, we quantified the age of first skin sores and scabies infection by pooling historical data from three studies conducted across five remote Aboriginal communities for children born between 2001 and 2005. We estimated the age of the first infection using the Kaplan-Meier estimator; parametric exponential mixture model; and Cox proportional hazards. For skin sores, the mean age of the first infection was approximately 10 months and the median was 7 months, with some heterogeneity in median observed by the community. For scabies, the mean age of the first infection was approximately 9 months and the median was 8 months, with significant heterogeneity by the community and an enhanced risk for children born between October and December. The young age of the first infection with skin sores and scabies reflects the high disease burden in these communities.


Asunto(s)
Nativos de Hawái y Otras Islas del Pacífico , Salud Rural , Escabiosis/transmisión , Úlcera Cutánea/microbiología , Infecciones Estreptocócicas/transmisión , Streptococcus pyogenes , Factores de Edad , Preescolar , Costo de Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Modelos Biológicos , Northern Territory/epidemiología , Prevalencia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Escabiosis/etnología , Úlcera Cutánea/etnología , Infecciones Estreptocócicas/etnología
5.
Vaccine ; 36(19): 2650-2656, 2018 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-29627233

RESUMEN

BACKGROUND: Most studies use indirect cohort or case-control methods to estimate vaccine effectiveness (VE) of 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) against invasive pneumococcal disease (IPD). Neither method can measure the benefit vaccination programs afford the unvaccinated and many studies were unable to estimate dose-specific VE. We linked Australia's national immunisation register with health data from two states to calculate IPD incidence by vaccination status and VE for a 3 + 0 PCV schedule (doses at 2, 4, 6 months, no booster) among a cohort of 1.4 million births. METHODS: Births records for 2001-2012 were probabilistically linked to IPD notifications, hospitalisations, deaths, and vaccination history (available until December 2013). IPD rates in vaccinated and unvaccinated children <2 years old were compared using Cox proportional hazards models (adjusting for potential confounders), with VE = (1 - adjusted hazard ratio) × 100. Separate models were performed for all-cause, PCV7, PCV13 and PCV13-non-PCV7 serotype-specific IPD, and for Aboriginal and non-Aboriginal children. RESULTS: Following introduction of universal PCV7 in 2005, rates of PCV7 serotype and all-cause IPD in unvaccinated children declined 89.5% and 61.4%, respectively, to be similar to rates in vaccinated children. Among non-Aboriginal children, VEs for 3 doses were 94.2% (95%CI: 81.9-98.1) for PCV7 serotype-specific IPD, 85.6% (95%CI: 60.5-94.8) for PCV13-non-PCV7 serotype-specific IPD and 80.1% (95%CI: 59.4-90.3) for all-cause IPD. There were no statistically significant differences between the VEs for 3 doses and for 1 or 2 doses against PCV13 and PCV13-non-PCV7 serotype-specific IPD, or between Aboriginal and non-Aboriginal children. CONCLUSION: Our population-based cohort study demonstrates that >90% coverage in the first year of a universal 3 + 0 PCV program provided high population-level protection, predominantly attributable to strong herd effects. The size of the cohort enabled calculation of robust dose-specific VE estimates for important population sub-groups relevant to vaccination policies internationally.


Asunto(s)
Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Australia/epidemiología , Estudios de Cohortes , Vacuna Neumocócica Conjugada Heptavalente/administración & dosificación , Vacuna Neumocócica Conjugada Heptavalente/uso terapéutico , Humanos , Programas de Inmunización , Esquemas de Inmunización , Lactante , Infecciones Neumocócicas/epidemiología , Vacunas Neumococicas/uso terapéutico , Estudios Retrospectivos , Serogrupo , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/patogenicidad , Cobertura de Vacunación
6.
Hum Mol Genet ; 27(3): 440-450, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29186532

RESUMEN

Depression and anxiety are the most common mental health conditions during pregnancy and can impair the normal development of mother-infant interactions. These adversities are associated with low birth weight and increased risk of behavioural disorders in children. We recently reported reduced expression of the imprinted gene PATERNALLY EXPRESSED GENE 3 (PEG3) in placenta of human infants born to depressed mothers. Expression of Peg3 in the brain has previously been linked maternal behaviour in rodents, at least in some studies, with mutant dams neglecting their pups. However, in our human study decreased expression was in the placenta derived from the fetus. Here, we examined maternal behaviour in response to reduced expression of Peg3 in the feto-placental unit. Prenatally we found novelty reactivity was altered in wild-type females carrying litters with a null mutation in Peg3. This behavioural alteration was short-lived and there were no significant differences the transcriptomes of either the maternal hypothalamus or hippocampus at E16.5. In contrast, while maternal gross maternal care was intact postnatally, the exposed dams were significantly slower to retrieve their pups and displayed a marked increase in anxiety. We also observed a significant reduction in the isolation-induced ultrasonic vocalizations (USVs) emitted by mutant pups separated from their mothers. USVs are a form of communication known to elicit maternal care suggesting Peg3 mutant pups drive the deficit in maternal behaviour. These data support the hypothesis that reduced placental PEG3 in human pregnancies occurs as a consequence of prenatal depression but leaves scope for feto-placental Peg3 dosage, during gestation, influencing aspects of maternal behaviour.


Asunto(s)
Factores de Transcripción de Tipo Kruppel/metabolismo , Ultrasonido , Vocalización Animal/fisiología , Animales , Animales Recién Nacidos , Ansiedad/genética , Depresión/genética , Femenino , Hipocampo/metabolismo , Hipotálamo/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Conducta Materna/fisiología , Ratones , Ratones Noqueados , Embarazo
7.
Epidemiol Infect ; 146(2): 207-217, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29208060

RESUMEN

Pertussis morbidity is highest in infants too young to be fully protected by routine vaccination schedules. Alternate vaccine strategies are required to maximise protection in this age-group. To understand baseline pertussis epidemiology prior to the introduction of the maternal pertussis vaccination program in 2014, we conducted a retrospective case series analyses of 53 901 notifications and temporal trends from 1997 to 2014. Notifications were highest in infants younger than 4 months of age and highest annual notification rates in infants younger than 1 month of age (308/100 000 per year). Amongst Aboriginal and Torres Strait Islander infants aged younger than 1 month, this rate was 576/100 000 per year. Notification rates were 40% higher amongst women 15-44 years, 62·4/100 000 population compared with men (44·5/100 000) and 90% higher in Aboriginal and Torres Strait Islander women of the same age (38·2/100 000) compared with men (19·7/100 000). Six infant deaths were identified, all younger than 2 months of age. Monitoring epidemiology in at-risk groups - infants too young to be vaccinated, women of childbearing age and Aboriginal and Torres Strait Islander peoples - following implementation of the maternal pertussis vaccination program will be important to assess its impact and safety.


Asunto(s)
Etnicidad/estadística & datos numéricos , Madres/estadística & datos numéricos , Tos Ferina/epidemiología , Adolescente , Adulto , Factores de Edad , Femenino , Humanos , Programas de Inmunización , Lactante , Recién Nacido , Masculino , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Vacuna contra la Tos Ferina/uso terapéutico , Queensland/epidemiología , Estudios Retrospectivos , Población Blanca/estadística & datos numéricos , Tos Ferina/prevención & control , Adulto Joven
8.
Int J Popul Data Sci ; 2(1): 406, 2017 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-32934996

RESUMEN

INTRODUCTION: Several countries have developed national immunisation registers, but only the Nordic countries have linked their registers to other health data in order to comprehensively evaluate the `real world' effectiveness of vaccines. Nordic countries can link datasets deterministically using the national person identifier, but most countries, including Australia, don't have such an identifier to enable this type of linkage. OBJECTIVES: To describe the process for assembling a linked study cohort that will enable the conduct of population-based studies related to immunisation and immunisation policy. METHODS: National death and immunisation databases along with state health data (notifications of vaccine preventable diseases, perinatal data, hospital admissions and emergency department presentations) up until December 2013 were probabilistically linked (using demographic details) for children born between 1996 and 2012 in two states: Western Australia and New South Wales (42% of Australia's population, combined). RESULTS: After exclusions there were 1.95 million children in the study cohort (live born children with both a birth and perinatal record which represents 97.5% of all live births in the state perinatal data collections - our source population) and 18.0 million person years of follow up (mean: 9.2 years per child). The characteristics of children in the cohort were generally similar to those only included in state perinatal databases and outcome measures were in keeping with expected figures from unlinked data sources. However, the lack of a dynamic national population register meant immigrants could not be included. CONCLUSIONS: We have been able to develop a similarly comprehensive system to the Nordic countries based on probabilistic linkage methods. Our experience should provide encouragement to other countries with national immunisation registers looking to establish similar systems.

9.
Eye (Lond) ; 30(6): 843-9, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27034203

RESUMEN

PurposeThe purpose of this study is to present the outcomes of a series of patients with choroidal neovascular membrane (choroidal neovascularisation (CNV)) secondary to a choroidal osteoma undergoing anti-VEGF monotherapy.Patients and methodsRetrospective series of patients with choroidal neovascularization secondary to choroidal osteoma. All patients underwent clinical and imaging assessment (fundus photo, B-scan ultrasonography, fluorescein angiography, and optical coherence tomography-where available), and were managed with intravitreal anti-VEGF injections (Bevacizumab). Visual acuity and central retinal thickness were recorded pre treatment and at the end of the follow-up period.ResultsEight patients were included in this study. Of this, 6/8 had predominantly classic or classic and 2/8 patients had minimally classic or occult CNV. Each patient received 3-10 injections of bevacizumab. Median follow-up was 9 months (3-15 months). Visual acuity improved in 5 patients, by 2-6 Snellen lines. CNV completely regressed in 5 cases and partially regressed in 3 cases. Mean CRT reduction was 122 µm (6 to -230 µm).ConclusionIntravitreal bevacizumab can be an effective treatment modality in the management of vision threatening CNV secondary to choroidal osteoma.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Coristoma/tratamiento farmacológico , Neoplasias de la Coroides/tratamiento farmacológico , Neovascularización Coroidal/tratamiento farmacológico , Osteoma , Adolescente , Adulto , Anciano , Coristoma/complicaciones , Neoplasias de la Coroides/complicaciones , Neoplasias de la Coroides/diagnóstico , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/etiología , Femenino , Angiografía con Fluoresceína , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
10.
Hum Vaccin Immunother ; 12(4): 848-56, 2016 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-26857450

RESUMEN

Maternal immunization has the potential to reduce the burden of infectious diseases in the pregnant woman and her infant. Many countries now recommend immunization against influenza at any stage of pregnancy and against pertussis in the third trimester. Despite evidence of the safety and effectiveness of these vaccines when administered during pregnancy, uptake generally remains low for influenza and moderate for pertussis vaccine. Enhancing confidence in both immunization providers and pregnant women by increasing the evidence-base for the safety and effectiveness of vaccines during pregnancy, improving communication and access by incorporating immunization into standard models of antenatal care are likely to improve uptake. Developing a framework for implementation of vaccines for pregnant women which is cognizant of local and national cultural, epidemiological, behavioral and societal factors will enable a smooth transition and high uptake for new vaccines currently in development for pregnant women.


Asunto(s)
Vacunas contra la Influenza , Vacuna contra la Tos Ferina , Complicaciones Infecciosas del Embarazo/prevención & control , Mujeres Embarazadas , Vacunas , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Femenino , Humanos , Lactante , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/efectos adversos , Gripe Humana/prevención & control , Vacuna contra la Tos Ferina/administración & dosificación , Vacuna contra la Tos Ferina/efectos adversos , Embarazo , Tercer Trimestre del Embarazo , Vacunación , Vacunas/administración & dosificación , Vacunas/efectos adversos , Tos Ferina/prevención & control
11.
Clin Infect Dis ; 52(2): 191-9, 2011 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-21288843

RESUMEN

UNLABELLED: The human rotavirus vaccine was evaluated during an outbreak of rotavirus G2P[4] infection in central Australia. No overall protective effect against hospitalization was demonstrated, raising concerns over the durability of vaccine protection against heterotypic strains. BACKGROUND: Two and a half years after commencing routine vaccination with human rotavirus vaccine, an outbreak of rotavirus G2P[4] infection occurred in central Australia. Vaccine effectiveness against a P[8]-containing strain (G9P[8]) had been demonstrated previously in this setting. This subsequent outbreak provided the opportunity to evaluate vaccine effectiveness against hospitalizations for a non-vaccine-related genotype in the same population. METHODS: A case-control study was nested within a cohort of vaccine-eligible children listed on a population-based immunization register. Children with rotavirus-confirmed gastroenteritis were individually matched by date of birth and Indigenous status with 4 control subjects. RESULTS: Forty-one cases met the inclusion criteria, and 21 were severe cases among infants aged <12 months. Nineteen (46%) of 41 case patients had received 2 doses of human rotavirus vaccine, compared with 87 (53%) of 164 control subjects. Vaccine effectiveness against rotavirus-related hospitalization was 19% (odds ratio, .81; 95% confidence interval, .32-2.05) for 2 doses compared with none. On secondary analysis, there was evidence of a protective effect against disease complicated by acidosis in the subset of infants aged <12 months (odds ratio, .15; 95% confidence interval, .03-.84). CONCLUSIONS: Evidence was not found for an overall protective effect of human rotavirus vaccine against hospitalization for rotavirus disease in this setting. Post hoc analyses suggested a protective effect against severe disease in young infants.


Asunto(s)
Brotes de Enfermedades , Hospitalización/estadística & datos numéricos , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/prevención & control , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Australia/epidemiología , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Lactante , Masculino , Rotavirus/clasificación , Rotavirus/genética , Rotavirus/aislamiento & purificación
12.
Rural Remote Health ; 10(3): 1464, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20795756

RESUMEN

INTRODUCTION: Uptake of penicillin prophylaxis to prevent recurrent rheumatic fever and its sequela rheumatic heart disease (RHD) is not optimal in the Northern Territory of Australia. The Full Moon Strategy (the Strategy) was introduced in the Central Australian region in June 2006 to improve the uptake of prophylactic penicillin: clients and healthcare workers were encouraged to use the full moon as a cue for the timing of the 4 weekly prophylactic penicillin injection. OBJECTIVE: To determine the impact and effectiveness of the Strategy on knowledge and uptake of benzathine penicillin prophylaxis for clients at risk of RHD, and for primary healthcare workers in Central Australia. METHODS: Clients at risk of RHD in four remote Aboriginal communities and the town camps of Alice Springs were identified from the RHD database. Consenting clients or their carers were interviewed about their knowledge of the Strategy and the health promotional tools used. Their healthcare records were then reviewed for prophylaxis uptake 2 years prior to and 2 years following the introduction of the Strategy. Primary healthcare workers in the four remote communities who were available at the time of the study visit were interviewed about their knowledge and use of the Strategy and the health promotional tools. RESULTS: Fifty RHD clients and 19 healthcare workers were interviewed. Most were aware of the flipchart but less than half knew of the calendar poster, hand-held card or radio advertisement. Prophylaxis uptake increased significantly from 47% in the 2 years prior to the introduction of the Strategy, to 57% 2 years after the Strategy was introduced. CONCLUSION: Introduction of the Strategy coincided with an improvement in uptake of prophylaxis but not around the time of the full moon. Uptake of benzathine penicillin remains inadequate and further innovative measures are needed to control rheumatic fever and its sequela in Aboriginal and Torres Strait Islander people.


Asunto(s)
Antibacterianos/uso terapéutico , Profilaxis Antibiótica/métodos , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Penicilina G Benzatina/uso terapéutico , Fiebre Reumática/prevención & control , Servicios de Salud Rural/organización & administración , Adolescente , Adulto , Prescripciones de Medicamentos/estadística & datos numéricos , Revisión de la Utilización de Medicamentos , Femenino , Estudios de Seguimiento , Adhesión a Directriz/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Promoción de la Salud/organización & administración , Humanos , Masculino , Persona de Mediana Edad , Northern Territory , Fiebre Reumática/epidemiología , Factores de Riesgo , Adulto Joven
13.
Bull World Health Organ ; 88(2): 139-46, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20428371

RESUMEN

OBJECTIVE: To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) in preventing pneumonia, diagnosed radiologically according to World Health Organization (WHO) criteria, among indigenous infants in the Northern Territory of Australia. METHODS: We conducted a historical cohort study of consecutive indigenous birth cohorts between 1 April 1998 and 28 February 2005. Children were followed up to 18 months of age. The PCV7 programme commenced on 1 June 2001. All chest X-rays taken within 3 days of any hospitalization were assessed. The primary endpoint was a first episode of WHO-defined pneumonia requiring hospitalization. Cox proportional hazards models were used to compare disease incidence. FINDINGS: There were 526 pneumonia events among 10,600 children - an incidence of 3.3 per 1000 child-months; 183 episodes (34.8%) occurred before 5 months of age and 247 (47.0%) by 7 months. Of the children studied, 27% had received 3 doses of vaccine by 7 months of age. Hazard ratios for endpoint pneumonia were 1.01 for 1 versus 0 doses; 1.03 for 2 versus 0 doses; and 0.84 for 3 versus 0 doses. CONCLUSION: There was limited evidence that PCV7 reduced the incidence of radiologically confirmed pneumonia among Northern Territory indigenous infants, although there was a non-significant trend towards an effect after receipt of the third dose. These findings might be explained by lack of timely vaccination and/or occurrence of disease at an early age. Additionally, the relative contribution of vaccine-type pneumococcus to severe pneumonia in a setting where multiple other pathogens are prevalent may differ with respect to other settings where vaccine efficacy has been clearly established.


Asunto(s)
Nativos de Hawái y Otras Islas del Pacífico , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Neumonía Neumocócica/diagnóstico por imagen , Neumonía Neumocócica/prevención & control , Factores de Edad , Australia , Estudios de Cohortes , Femenino , Humanos , Incidencia , Lactante , Masculino , Neumonía Neumocócica/etnología , Radiografía , Factores de Tiempo , Vacunas Conjugadas
14.
J Med Genet ; 47(2): 120-5, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19581274

RESUMEN

BACKGROUND: Primary open angle glaucoma is a progressive optic neuropathy characterised by the selective loss of retinal ganglion cells, pathological optic disc cupping and visual field defects. The OPA1 gene encodes an inner mitochondrial membrane protein crucial for normal mitochondrial function, and pathogenic mutations cause autosomal dominant optic atrophy by specifically targeting retinal ganglion cells. This raises the distinct possibility that more subtle genetic variations in OPA1 could alter the risk of developing glaucoma. METHODS: 137 patients with primary open angle glaucoma (67 patients with high-tension glaucoma (HTG), 70 patients with normal-tension glaucoma (NTG)) and 75 controls from the North East of England were studied. Three single-nucleotide polymorphisms in intron 8 (IVS8+4c-->t and IVS8+32t-->c) and exon 4 (c.473A-->G) of the OPA1 gene were genotyped in the study group. In addition, the entire OPA1 coding region was sequenced in 24 individuals with the CT/TT compound genotype using standard BigDye chemistries. RESULTS: There was no difference in either allele or genotype frequency for the IVS8+32t-->c single-nucleotide polymorphisms between patients and controls, but there was a significant association between the T allele at IVS8+4c-->t and the risk of developing NTG (OR=2.04, 95% CI=1.10 to 3.81, p=0.004), but not HTG. Logistic regression analysis also confirmed a strong association between the CT/TT compound genotype at IVS8+4 and IVS8+32 with NTG (OR=29.75, 95% CI=3.83 to 231.21, p=0.001). CONCLUSIONS: The CT/TT compound genotype at IVS8+4 and IVS8+32 is a strong genetic risk determinant for NTG but not HTG.


Asunto(s)
GTP Fosfohidrolasas/genética , Glaucoma de Ángulo Abierto/genética , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Intrones , Modelos Logísticos , Datos de Secuencia Molecular , Polimorfismo de Nucleótido Simple , Alineación de Secuencia
15.
Epidemiol Infect ; 137(2): 194-202, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18559126

RESUMEN

This study describes the epidemiology of community-acquired pneumonia (CAP) in elderly Australians for the first time. Using a case-cohort design, cases with CAP were in-patients aged > or = 65 years with ICD-10-AM codes J10-J18 admitted over 2 years to two tertiary hospitals. The cohort sample was randomly selected from all hospital discharges, frequency-matched to cases by month. Logistic regression was used to estimate risk ratios for factors predicting CAP or associated mortality. A total of 4772 in-patients were studied. There were 1952 cases with CAP that represented 4% of all elderly admissions: mean length of stay was 9.0 days and 30-day mortality was 18%. Excluding chest radiograph, 520/1864 (28%) cases had no investigations performed. The strongest predictors of CAP were previous pneumonia, history of other respiratory disease, and aspiration. Intensive-care-unit admission, renal disease and increasing age were the strongest predictors of mortality, while influenza vaccination conferred protection. Hospitalization with CAP in the elderly is common, frequently fatal and a considerable burden to the Australian community. Investigation is ad hoc and management empirical. Influenza vaccination is associated with reduced mortality. Patient characteristics can predict risk of CAP and subsequent mortality.


Asunto(s)
Infecciones Comunitarias Adquiridas/epidemiología , Neumonía/epidemiología , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Estudios de Cohortes , Infecciones Comunitarias Adquiridas/mortalidad , Femenino , Hospitalización , Humanos , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Tiempo de Internación , Masculino , Neumonía/mortalidad , Factores de Riesgo
16.
Cochrane Database Syst Rev ; (1): CD000422, 2008 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-18253977

RESUMEN

BACKGROUND: Diseases caused by Streptococcus pneumoniae(S. pneumoniae) continue to cause substantial morbidity and mortality throughout the world. Whilst pneumococcal polysaccharide vaccines (PPV) have the potential to prevent disease and death, the degree of protection afforded against various clinical endpoints and within different populations is uncertain. OBJECTIVES: To assess the effectiveness of PPV in preventing disease or death in adults. Adverse events were not assessed. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2); MEDLINE (January 1966 to June 2007); and EMBASE (1974 to June 2007). SELECTION CRITERIA: A) Randomised controlled trials (RCTs) comparing PPV with placebo, control vaccines, or no intervention.B) Non-RCTs assessing PPV effectiveness against invasive pneumococcal disease (IPD). DATA COLLECTION AND ANALYSIS: A) RCTs: trial quality assessment was conducted by two review authors and data extracted by three authors; odds ratios (OR) and 95% confidence intervals (CI) were estimated using a random-effects model.B) Non-RCTs: study quality, including measures to control for confounding, was assessed and data extracted by two review authors; OR and 95% CI were calculated using a random-effects model following the conversion of each study outcome to a log OR and standard error. MAIN RESULTS: Twenty-two studies met our inclusion criteria (15 RCTs involving 48,656 participants and 7 non-RCTs involving 62,294 participants). Meta-analysis of the RCTs found strong evidence of PPV efficacy against IPD with no statistical heterogeneity (OR 0.26, 95% CI 0.15 to 0.46; random-effects model, I-squared (I(2)) = 0%). Efficacy against all cause pneumonia was inconclusive with substantial statistical heterogeneity (OR 0.71, 95% CI 0.52 to 0.97; random-effects model, I(2) = 87.3%). PPV was not associated with substantial reductions in all-cause mortality (OR 0.87, 95% CI 0.69 to 1.10; random-effects model, I(2) = 75.3%). Vaccine efficacy against primary outcomes appeared poorer in adults with chronic illness but the difference was not statistically significant. Non-RCTs provided evidence for protection against IPD in populations for whom the vaccine is currently utilised (OR 0.48, 95% CI 0.37 to 0.61; random-effects model, I(2) = 31.4%). AUTHORS' CONCLUSIONS: This meta-analysis provides evidence supporting the recommendation for PPV to prevent IPD in adults. The evidence from RCTs is less clear with respect to adults with chronic illness. This might be because of lack of effect or lack of power in the studies. The meta-analysis does not provide compelling evidence to support the routine use of PPV to prevent all-cause pneumonia or mortality.


Asunto(s)
Vacunas Neumococicas/uso terapéutico , Neumonía Neumocócica/prevención & control , Adulto , Anciano , Estudios de Casos y Controles , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Epidemiol Infect ; 136(2): 232-40, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17445319

RESUMEN

This study examines the validity of using ICD-10 codes to identify hospitalized pneumonia cases. Using a case-cohort design, subjects were randomly selected from monthly cohorts of patients aged > or = 65 years discharged from April 2000 to March 2002 from two large tertiary Australian hospitals. Cases had ICD-10-AM codes J10-J18 (pneumonia); the cohort sample was randomly selected from all discharges, frequency matched to cases by month. Codes were validated against three comparators: medical record notation of pneumonia, chest radiograph (CXR) report and both. Notation of pneumonia was determined for 5098/5101 eligible patients, and CXR reports reviewed for 3349/3464 (97%) patients with a CXR. Coding performed best against notation of pneumonia: kappa 0.95, sensitivity 97.8% (95% CI 97.1-98.3), specificity 96.9% (95% CI 96.2-97.5), positive predictive value (PPV) 96.2% (95% CI 95.4-97.0) and negative predictive value (NPV) 98.2% (95% CI 97.6-98.6). When medical record notation of pneumonia is used as the standard, ICD-10 codes are a valid method for retrospective ascertainment of hospitalized pneumonia cases and appear superior to use of complexes of symptoms and signs, or radiology reports.


Asunto(s)
Clasificación Internacional de Enfermedades/estadística & datos numéricos , Neumonía/epidemiología , Vigilancia de la Población/métodos , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Femenino , Hospitales , Humanos , Masculino , Registros Médicos/estadística & datos numéricos , Valor Predictivo de las Pruebas , Radiografía Torácica/estadística & datos numéricos , Sensibilidad y Especificidad
18.
Epidemiol Infect ; 136(2): 225-31, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17359564

RESUMEN

Invasive pneumococcal disease (IPD) notifications are used to monitor IPD vaccination programmes. We conducted sequential deterministic data-linkage between IPD notifications and hospitalization data in Victoria, Australia, in order to determine whether all diagnosed cases were being reported. The proportion of each relevant hospital admission ICD-10-AM code that could be linked to notified cases was calculated. Total and age-specific annual rates were calculated and compared for notified and non-notified cases. Total incidence was estimated using data-linkage results and application of a two-source capture-recapture method. The first 2 years of IPD surveillance in Victoria missed at least one-sixth of laboratory-confirmed IPD cases. Estimated annual IPD rate increased from 9.0 to 10.7/100,000 and rose even higher, to 11.5/100,000, with age-specific rates possibly reaching 90.0/100,000 children aged <2 years, when using capture-recapture. Strategies to improve notification and coding of hospitalized cases of IPD are required.


Asunto(s)
Notificación de Enfermedades/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Infecciones Neumocócicas/epidemiología , Vigilancia de la Población/métodos , Adulto , Factores de Edad , Investigación sobre Servicios de Salud , Humanos , Incidencia , Lactante , Recién Nacido , Victoria/epidemiología
19.
Rural Remote Health ; 7(3): 687, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17650060

RESUMEN

INTRODUCTION: Although parents in developed market economies regard head lice infections (pediculosis) as a significant problem, health departments generally rate pediculosis as a low priority health issue, encouraging parents to manage and control it. But how well equipped and willing are parents to manage the infections? There do not appear to be any studies in the literature addressing these issues. This article presents the results of a survey conducted in Australia that aimed to answer these questions. METHODS: A cross-sectional survey of parents of primary school aged children in Victoria (Vic) and north Queensland (NQ) was conducted using a self-administered questionnaire. The study investigated the knowledge, attitudes and practices of parents regarding head lice infections. RESULTS: Only 7.1% of 1338 who completed the questionnaire answered all 10 knowledge questions correctly and more than one-third failed to answer half correctly. There was a weak negative correlation between parents' knowledge and the prevalence of active pediculosis in the school. Almost all parents wanted the responsibility for treating pediculosis and more than three-quarters saw it as a health concern. A higher proportion of parents in NQ used preventative strategies (67% vs 41%). Most parents spent less than AU$50 per year on treatments. Alarmingly, however, the proportion of children missing school as a result of pediculosis was 24.4% and 30.3% in Vic and NQ, respectively. In Vic there was a positive correlation (r = 0.39) between missing school in the previous 12 months and prevalence of pediculosis in the school. CONCLUSIONS: This appears to be the most comprehensive study of parental knowledge, beliefs, and practices regarding head lice infections. Although parents wanted responsibility for the management of pediculosis, deficiencies in their knowledge indicate they may be inadequately equipped to do so. Given the high proportion of children in both states who have missed school as a result of head lice, it is recommended that health departments in Australia should work to ensure that consistent and accurate messages about pediculosis are disseminated, and that relevant legislation is amended to prevent children being excluded from school.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Infestaciones por Piojos/prevención & control , Padres , Pediculus , Dermatosis del Cuero Cabelludo/prevención & control , Absentismo , Animales , Niño , Estudios Transversales , Costos de la Atención en Salud , Humanos , Infestaciones por Piojos/economía , Queensland , Dermatosis del Cuero Cabelludo/economía , Estudiantes , Victoria
20.
Epidemiol Infect ; 135(8): 1363-8, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17352839

RESUMEN

For jurisdictions implementing measles elimination strategies, a minimum surveillance benchmark of 1/100 000 population per year measles-like illness (MLI) cases initially notified, but then rejected based on laboratory testing was proposed. We used this standard to assess the quality of the Victorian enhanced measles surveillance between 1998 and 2003. Victorian enhanced measles surveillance includes interviews with notified cases and confirmatory laboratory testing for notifications. We found 72% (918/1281) of measles notifications were discarded after testing. The median annual rate of discard was 2.9/100 000. The annual discard rate was inversely associated with the age of the notifications, and measles negative with no other diagnosis made was the most common laboratory outcome. The annual rates of discarded notifications in Victoria were consistently above the minimum recommended standard. The rate of discarded MLIs as a surveillance threshold should be useful in measles endemic regions, but may require modification where disease elimination has occurred.


Asunto(s)
Notificación de Enfermedades/estadística & datos numéricos , Investigación sobre Servicios de Salud , Sarampión/epidemiología , Sarampión/prevención & control , Humanos , Sarampión/diagnóstico , Victoria/epidemiología
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