Transmission parameters of the 2001 foot and mouth epidemic in Great Britain.

Despite intensive ongoing research, key aspects of the spatial-temporal evolution of the 2001 foot and mouth disease (FMD) epidemic in Great Britain (GB) remain unexplained. Here we develop a Markov Chain Monte Carlo (MCMC) method for estimating epidemiological parameters of the 2001 outbreak for a range of simple transmission models. We make the simplifying assumption that infectious farms were completely observed in 2001, equivalent to assuming that farms that were proactively culled but not diagnosed with FMD were not infectious, even if some were infected. We estimate how transmission parameters varied through time, highlighting the impact of the control measures on the progression of the epidemic. We demonstrate statistically significant evidence for assortative contact patterns between animals of the same species. Predictive risk maps of the transmission potential in different geographic areas of GB are presented for the fitted models

Clinical implications of Plasmodium resistance to atovaquone/proguanil: a systematic review and meta-analysis.

Background: Atovaquone/proguanil, registered as Malarone®, is a fixed-dose combination recommended for first-line treatment of uncomplicated Plasmodium falciparum malaria in non-endemic countries and its prevention in travellers. Mutations in the cytochrome bc1 complex are causally associated with atovaquone resistance. Methods: This systematic review assesses the clinical efficacy of atovaquone/proguanil treatment of uncomplicated malaria and examines the extent to which codon 268 mutation in cytochrome b influences treatment failure and recrudescence based on published information. Results: Data suggest that atovaquone/proguanil treatment efficacy is 89%-98% for P. falciparum malaria (from 27 studies including between 18 and 253 patients in each case) and 20%-26% for Plasmodium vivax malaria (from 1 study including 25 patients). The in vitro P. falciparum phenotype of atovaquone resistance is an IC50 value >28 nM. Case report analyses predict that recrudescence in a patient presenting with parasites carrying cytochrome b codon 268 mutation will occur on average at day 29 (95% CI: 22, 35), 19 (95% CI: 7, 30) days longer than if the mutation is absent. Conclusions: Evidence suggests atovaquone/proguanil treatment for P. falciparum malaria is effective. Late treatment failure is likely to be associated with a codon 268 mutation in cytochrome b, though recent evidence from animal models suggests these mutations may not spread within the population. However, early treatment failure is likely to arise through alternative mechanisms, requiring further investigation

Predictors of mortality in primary antiphospholipid syndrome. A single-centre cohort study.

The vascular mortality of antiphospholipid syndrome (APS) ranges from 1.4 % to 5.5 %, but its predictors are poorly known. It was the study objective to evaluate the impact of baseline lupus anticoagulant assays, IgG anticardiolipin (aCL), plasma fibrinogen (FNG) and von Willebrand factor (VWF), platelets (PLT) and of genetic polymorphisms of methylenetetrahydrofolate reductase C677T, of prothrombin G20210A and of paraoxonase-1 Q192R on mortality in primary APS (PAPS). Cohort study on 77 thrombotic PAPS and 33 asymptomatic carriers of aPL (PCaPL) seen from 1989 to 2015 and persistently positive for aPL as per annual review. At baseline all participants were tested twice for the ratios of kaolin clotting time (KCTr), activated partial thromboplastin time (aPTTr), dilute Russell viper venom time (DRVVTr), IgG aCL, FNG, VWF and once for PLT. All thrombotic PAPS were on warfarin with regular INR monitoring. During follow-up 11 PAPS deceased (D-PAPS) of recurrent thrombosis despite adequate anticoagulation yielding an overall vascular mortality of 10 %. D-PAPS had the strongest baseline aPTTr and DRVVTr and the highest mean baseline IgG aCL, FNG, VWF and PLT. Cox proportional hazards model identified baseline DRVVTr and FNG as main predictors of mortality with adjusted hazard ratios of 5.75 (95 % confidence interval [CI]: 1.5, 22.4) and of 1.03 (95 %CI: 1.01, 1.04), respectively. In conclusion, plasma DRVVTr and FNG are strong predictors of vascular mortality in PAPS; while FNG lowering agents exist further research should be directed at therapeutic strategies able to dampen aPL production

The dynamics and outcomes of AKI progression during the COVID-19 pandemic.

PURPOSE: Acute kidney injury (AKI) associated with COVID-19 is associated with poor prognosis. This study assessed the hitherto uninvestigated impact of COVID-19 on the progression and clinical outcomes of patients with AKI. METHODS: Data from 576 patients with AKI admitted between 13/3/20 and 13/5/20 were studied. Increasingly complex analyses, from logistic regressions to competing-risk and multi-state models, have revealed insights into AKI progression dynamics associated with PCR-confirmed COVID-19 acquisition and death. Meta-analyses of case fatality ratios among patients with AKI were also conducted. RESULTS: The overall case-fatality ratio was 0.33 [95% CI (0.20-0.36)]; higher in COVID-19 positive (COVID+) patients 0.52 [95% CI (0.46-0.58)] than in their negative (COVID-) counterparts 0.16 [95% CI (0.12-0.20)]. In AKI Stage-3 patients, that was 0.71 [95% CI (0.64-0.79)] among COVID+ patients with 45% dead within 14 days and 0.35 [95% CI (0.25-0.44)] in the COVID- group and 28% died within 14 days. Among patients diagnosed with AKI Stage-1 within 24 h, the probability of progression to AKI Stage-3 on day 7 post admission was 0.22 [95% CI (0.17-0.27)] among COVID+ patients, and 0.06 [95% CI (0.03, 0.09)] among those who tested negative. The probability of discharge by day 7 was 0.71 [95% CI (0.66, 0.75)] in COVID- patients, and 0.27 [95% CI (0.21, 0.32)] in COVID+ patients. By day 14, in AKI Stage-3 COVID+ patients, that was 0.35 [95% CI (0.25, 0.44)] with little change by day 10, that is, 0.38 [95% CI (0.29, 0.47)]. CONCLUSION: These results are consistent with either a rapid progression in severity, prolonged hospital care, or high case fatality ratio among AKI Stage-3 patients, significantly exacerbated by COVID-19 infection

The epidemiology of soil-transmitted helminth infections in children up to 8 years of age: Findings from an Ecuadorian birth cohort.

BACKGROUND: There are few prospective longitudinal studies of soil-transmitted helminth (STH) infections during early childhood. We studied the epidemiology of and risk factors for soil-transmitted helminth infections from birth to 8 years of age in tropical Ecuador. METHODS: 2,404 newborns were followed to 8 years of age with periodic stool sample collections. Stool samples were collected also from household members at the time of the child's birth and examined by microscopy. Data on social, environmental, and demographic characteristics were collected by maternal questionnaire. Associations between potential risk factors and STH infections were estimated using generalized estimated equations applied to longitudinal binary outcomes for presence or absence of infections at collection times. RESULTS: Of 2,404 children, 1,120 (46.6%) were infected with at least one STH infection during the first 8 years of life. The risk of A. lumbricoides (16.2%) was greatest at 3 years, while risks of any STH (25.1%) and T. trichiura (16.5%) peaked at 5 years. Factors significantly associated with any STH infection in multivariable analyses included age, day-care (OR 1.34, 95% CI 1.03-1.73), maternal Afro-Ecuadorian ethnicity (non-Afro vs. Afro, OR 0.55, 95% CI 0.43-0.70) and lower educational level (secondary vs. illiterate, OR 0.31, 95% CI 0.22-0.45)), household overcrowding (OR 1.53, 95% CI 1.21-1.94)), having a latrine rather than a water closet (WC vs. latrine, OR 0.77, 95% CI 0.62-0.95)), and STH infections among household members (OR 2.03, 95% CI 1.59-2.58)). T. trichiura was more associated with poverty (high vs. low socioeconomic status, OR, 0.63, 95% CI 0.40-0.99)] and presence of infected siblings in the household (OR 3.42, 95% CI 2.24-5.22). CONCLUSION: STH infections, principally with A. lumbricoides and T. trichiura, peaked between 3 and 5 years in this cohort of children in tropical Ecuador. STH infections among household members were an important determinant of infection risk and could be targeted for control and elimination strategies

Differences in symptoms and cardiopulmonary responses to Treadmill versus Cycle cardiopulmonary exercise testing and comparison with the 6MWT in ILD

Aims: Cardiopulmonary exercise testing (CPET) is used for diagnostic and prognostic reasons in Interstitial Lung Disease (ILD). Our aims were to compare symptoms and cardiopulmonary responses between a) cycle and treadmill walking and b) between CPET and the 6MWT. Methods: 18 ILD patients (6 IPF; 12M), mean (SD) age 65.4 (12.6), FVC% pred. 72.7 (20.7), DLCO% pred. 42.2 (13.4) underwent CPET by cycle ergometry (C-CPET) and treadmill walking (T-CPET) in random order, with 30-45 min rest between tests, on a single session. On a second session 3-7 days apart, patients performed the 6MWT. Oxygen saturation (SpO2), heart rate (HR), breathlessness (BORG score) and leg fatigue/exertion (RPE scale) were recorded at rest, peak and at each minute of the 3-min recovery. We used the sign rank test with the null hypothesis of no difference between responses to the 3 tests of multiple CPET and symptom parameters. Results: Data were consistent with no differences between C-CPET and T-CPET in cardiopulmonary parameters (PeakVO2 p value=0.4, AT_VO2 p= 0.5, Peak VE/VCO2 p= 0.5, Peak VE/VO2 = 0.8). Desaturation (∆SpO2) was similar between T- CPET and C-CPET (p= 0.4) or 6MWT (0.7) but differed between C-CPET and 6MWT (p=0.03). The 3-minute SpO2 recovery was slower in T-CPET than the other tests. Change in HR (∆HR) and 3-min recovery was similar between CPET modes (p=0.1) but statistically lower in the 6MWT (p= 0.001). Breathlessness was greater in T-CPET than C-CPET (∆BORG p= 0.04) and recovery slower than the other two tests. Patients with CTD-ILD reported a preference for T-CPET. Summary/Conclusions: Cardiopulmonary parameters can be derived accurately from both types of CPET. The drop in oxygen saturation at the 6MWT was similar to that of the maximal T-CPET so, it can be used in ILD patients to estimate level of desaturation, even though the 6MWT underestimates the delay in SpO2 recovery. Funding source: This abstract presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-1112-29067). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health, UK

A prospective seroepidemiological study of toxocariasis during early childhood in coastal Ecuador: potential for congenital transmission and risk factors for infection.

BACKGROUND: Although Toxocara spp. infection has a worldwide distribution, to our knowledge, no data from birth cohorts have been reported in published studies on the potential for congenital transmission and determinants of infection in early childhood. METHODS: We followed 290 mother-infant pairs from birth to 5 years of age through periodic collection of data and samples at birth, 7 and 13 months and 2, 3 and 5 years of age. Data on potential risk factors and confounders were collected by maternal questionnaire. Blood for plasma was collected from the mother at time of birth and periodically from the child for detection of anti-Toxocara spp. immunoglobulin G (IgG) antibodies using a Toxocara canis larval excretory-secretory antigen-based enzyme-linked immunosorbent assay. Stool samples were collected from the mother around the time of birth and periodically from the child for microscopic detection of soil-transmitted helminths (STH). Associations between potential risk factors and Toxocara spp. seroprevalence and seroconversion were estimated using multivariable logistic regression and generalized estimating equations. RESULTS: Toxocara spp. seroprevalence was 80.7% in mothers and in children was 0%, 9.3%, 48.4%, 64.9%, and 80.9% at 7 months, 13 months, 2, 3 and 5 years, respectively. Risk factors significantly associated with increases in seroprevalence over the first 5 years of life in multivariable analyses were age [Odds ratio (OR) 2.06, 95% confidence interval (CI) 1.39-2.27, P < 0001], male sex (female vs. male: OR 0.66, 95% CI 0.48-0.89, P = 0.006), maternal ethnicity (non-Afro vs. Afro-Ecuadorian: OR 0.65, 95% CI 0.47-0.91, P = 0.011), lower maternal educational and socioeconomic level, and childhood STH (OR 2.29, 95% CI 1.51-3.47, P < 0.001). Seroconversion rates for infection were greatest at 2 years of age (3.8%/month). Factors associated significantly with seroconversion at 2, 3 or 5 years were childhood STH infection, male sex, and more frequent domestic cat exposure. CONCLUSIONS: Our data, from an area of high Toxocara spp. endemicity, indicate no congenital transmission but high rates of seroconversion after 13 months of age reaching maternal levels of seroprevalence by 5 years of age. Factors associated with seroprevalence and seroconversion included STH infections, domestic cats, maternal ethnicity, male sex, STH infections, and markers of greater poverty

The Spread of Bluetongue Virus Serotype 8 in Great Britain and Its Control by Vaccination

Bluetongue (BT) is a viral disease of ruminants transmitted by Culicoides biting midges and has the ability to spread rapidly over large distances. In the summer of 2006, BTV serotype 8 (BTV-8) emerged for the first time in northern Europe, resulting in over 2000 infected farms by the end of the year. The virus subsequently overwintered and has since spread across much of Europe, causing tens of thousands of livestock deaths. In August 2007, BTV-8 reached Great Britain (GB), threatening the large and valuable livestock industry. A voluntary vaccination scheme was launched in GB in May 2008 and, in contrast with elsewhere in Europe, there were no reported cases in GB during 2008.Here, we use carefully parameterised mathematical models to investigate the spread of BTV in GB and its control by vaccination. In the absence of vaccination, the model predicted severe outbreaks of BTV, particularly for warmer temperatures. Vaccination was predicted to reduce the severity of epidemics, with the greatest reduction achieved for high levels (95%) of vaccine uptake. However, even at this level of uptake the model predicted some spread of BTV. The sensitivity of the predictions to vaccination parameters (time to full protection in cattle, vaccine efficacy), the shape of the transmission kernel and temperature dependence in the transmission of BTV between farms was assessed.A combination of lower temperatures and high levels of vaccine uptake (>80%) in the previously-affected areas are likely to be the major contributing factors in the control achieved in England in 2008. However, low levels of vaccination against BTV-8 or the introduction of other serotypes could result in further, potentially severe outbreaks in future

Impact of early life geohelminths on wheeze, asthma, and atopy in Ecuadorian children at 8 years.

BACKGROUND: Early-lifeexposures to geohelminths may protect against development of wheeze/asthma and atopy. OBJECTIVE: Study effect of maternal geohelminths and infections in children during the first 5 years on atopy, wheeze/asthma, and airways reactivity/inflammation at 8 years. METHODS: Birth cohort of 2,404 neonates followed to 8 years in rural Ecuador. Data on wheeze/asthma were collected by questionnaire and atopy by skin prick test (SPT) reactivity to 9 allergens. We measured airways reactivity to bronchodilator, fractional exhaled nitric oxide (FeNO), and nasal eosinophilia. Stool samples were examined for geohelminths by microscopy. RESULTS: 1,933 (80.4%) children were evaluated at 8 years. Geohelminths were detected in 45.8% of mothers and 45.5% of children to 5 years. Frequencies of outcomes at 8 years were: wheeze (6.6%), asthma between 5 and 8 years (7.9%), SPT (14.7%), airways reactivity (10%), and elevated FeNO (10.3%) and nasal eosinophilia (9.2%). Any maternal geohelminth was associated with reduced SPT prevalence (OR 0.72).Childhood Trichuris trichiura infectionsduring the first 5 years were associated with reduced wheeze (OR 0.57) but greater parasite burdens with Ascaris lumbricoidesat 5 years were associated with increased wheeze (OR 2.83) and asthma (OR 2.60). Associations between maternal geohelminths and wheeze/asthma were modified by atopy. Parasite-specificeffects on wheeze/asthma and airways reactivity and inflammation were observed in non-atopic children. CONCLUSIONS: Our data provide novel evidence for persistent effects of in utero geohelminth exposures on childhood atopy but highlight the complex nature of the relationship between geohelminths and the airways. Registered as an observational study (ISRCTN41239086)

The characteristics, dynamics and risk of death in COVID-19 positive dialysis patients in London, UK

Background: Dialysis patients, with frequent co-morbidities, advanced age and frailty, visiting treatment facilities frequently are perhaps more prone to SARS-Cov-2 infection and related death - the risk-factors and dynamics of which are unknown. The aim of this study was to investigate the hospital outcomes in SARS-CoV-2 infected dialysis patients. Methods: Data on 224 hemodialysis patients between 02/29/2020 and 05/15/2020 with confirmed SARS-CoV-2 were analyzed for outcomes and potential risk factors for death, using competing risk regression model assessed by sub-distribution hazards ratio (SHR). Results: Crude data analyses suggest an overall case fatality ratio of 22.7(95%CI(17.3-28.3)%) overall but that varies across age groups from 11.4(95%CI(0.9-9.2)) in 80 years; with 60% of deaths occurring in the first 15 days and 80% within 21 days indicating a rapid deterioration towards death after admission. Almost 90% of surviving patients were discharged within 28 days. Death was more likely than hospital discharge in more frail (WHO performance status 3-4) [SHR=2.16(1.25-3.74);p=0.006)], ischemic heart disease [SHR=2.28(1.32-3.94),p=0.003], cerebrovascular disease [SHR=2.11(1.20-3.72),p=0.010], smoking history [SHR=2.69(1.33-5.45),p=0.006], and (completely or partially) hospitalized patients [SHR=10.26.(3.10-33.94),p<.001]; and in patients with high CRP [SHR=1.35(1.10-1.67)] and high neutrophil:lymphocyte ratio [SHR=1.03(1.01-1.04),p<0.001]. Our data did not support differences in the risk of death associated with gender, ethnicity, dialysis vintage or other comorbidities. However, comparison with the entire dialysis population attending these hospitals, and 12.9% being affected, revealed that non-Caucasians (62% vs. 52% in all patients, p=0.001) and diabetic patients (54% vs. 22%, p<0.001) were disproportionately affected. Conclusion: This report discusses the outcomes of a large cohort of dialysis patients with SARS-CoV-2, infection affecting more diabetics and non-Caucasians; with a high case fatality ratio, which increased significantly with age, frailty, smoking, increasing CRP and neutrophil:lymphocyte ratio at presentation