Preliminary estimate of contribution of Arctic nitrogen fixation to the global nitrogen budget

Dinitrogen (N-2) fixation is the source of all biologically available nitrogen on earth, and its presence or absence impacts net primary production and global biogeochemical cycles. Here, we report rates of 3.5-17.2 nmol N L-1 d(-1) in the ice-free coastal Alaskan Arctic to show that N-2 fixation in the Arctic Ocean may be an important source of nitrogen to a seasonally nitrogen-limited system. If widespread in surface waters over ice-free shelves throughout the Arctic, N-2 fixation could contribute up to 3.5 Tg N yr(-1) to the Arctic nitrogen budget. At these rates, N-2 fixation occurring in ice-free summer waters would offset up to 27.1% of the Arctic denitrification deficit and contribute an additional 2.7% to N-2 fixation globally, making it an important consideration in the current debate of whether nitrogen in the global ocean is in steady state. Additional investigations of high-latitude marine diazotrophic physiology are required to refine these N-2 fixation estimates

Treating childhood pneumonia in hard-to-reach areas: A model-based comparison of mobile clinics and community-based care

BACKGROUND: Where hard-to-access populations (such as those living in insecure areas) lack access to basic health services, relief agencies, donors, and ministries of health face a dilemma in selecting the most effective intervention strategy. This paper uses a decision mathematical model to estimate the relative effectiveness of two alternative strategies, mobile clinics and fixed community-based health services, for antibiotic treatment of childhood pneumonia, the world's leading cause of child mortality. METHODS: A "Markov cycle tree" cohort model was developed in Excel with Visual Basic to compare the number of deaths from pneumonia in children aged 1 to 59 months expected under three scenarios: 1) No curative services available, 2) Curative services provided by a highly-skilled but intermittent mobile clinic, and 3) Curative services provided by a low-skilled community health post. Parameter values were informed by literature and expert interviews. Probabilistic sensitivity analyses were conducted for several plausible scenarios. RESULTS: We estimated median pneumonia-specific under-5 mortality rates of 0.51 (95% credible interval: 0.49 to 0.541) deaths per 10,000 child-days without treatment, 0.45 (95% CI: 0.43 to 0.48) with weekly mobile clinics, and 0.31 (95% CI: 0.29 to 0.32) with CHWs in fixed health posts. Sensitivity analyses found the fixed strategy superior, except when mobile clinics visited communities daily, where rates of care-seeking were substantially higher at mobile clinics than fixed posts, or where several variables simultaneously differed substantially from our baseline assumptions. CONCLUSIONS: Current evidence does not support the hypothesis that mobile clinics are more effective than CHWs. A CHW strategy therefore warrants consideration in high-mortality, hard-to-access areas. Uncertainty remains, and parameter values may vary across contexts, but the model allows preliminary findings to be updated as new or context-specific evidence becomes available. Decision analytic modelling can guide needed field-based research efforts in hard-to-access areas and offer evidence-based insights for decision-makers

Effect of Geographical Access to Health Facilities on Child Mortality in Rural Ethiopia: A Community Based Cross Sectional Study

BACKGROUND: There have been few studies that have examined associations between access to health care and child health outcomes in remote populations most in need of health services. This study assessed the effect of travel time and distance to health facilities on mortality in children under five years in a remote area of rural north-western Ethiopia. METHODS AND FINDINGS: This study involved a randomly selected cross sectional survey of 2,058 households. Data were collected during home visits to all resident women of reproductive age (15-49 years). A geographic information system (GIS) was used to map all households and the only health centre in the district. The analysis was restricted to 2,206 rural children who were under the age of five years during the five years before the survey. Data were analysed using random effects Poisson regression. 90.4% (1,996/2,206) of children lived more than 1.5 hours walk from the health centre. Children who lived ≥1.5 hrs from the health centre had a two to three fold greater risk of death than children who lived <1.5 hours from the health centre (children with travel time 1.5-<2.5 hrs adjusted relative risk [adjRR] 2.3[0.95-5.6], travel time 2.5-<3.5 hrs adjRR 3.1[1.3-7.4] and travel time 3.5-<6.5 hrs adjRR 2.5[1.1-6.2]). CONCLUSION: Distance to a health centre had a marked influence on under five mortality in a poor, rural, remote area of Ethiopia. This study provides important information for policy makers on the likely impact of new health centres and their most effective location in remote areas

Measuring Under-Five Mortality: Validation of New Low-Cost Methods

n/

Impact of Lack of Breast Feeding during Neonatal Age on the Development of Clinical Signs of Pneumonia and Hypoxemia in Young Infants with Diarrhea

Hypoxemia is a grave sequel of pneumonia, and an important predictor of a fatal outcome. Pneumonia in the neonatal period is often associated with lack of breast feeding. However, there is no published report on the impact of the cessation of breast feeding in the neonatal period on the development of pneumonia and hypoxemia. The purpose of our study was to assess the impact of non-breast feeding or stopping breast feeding during the neonatal period (henceforth to be referred to as non-breast fed) on clinical features of pneumonia and hypoxemia in 0-6-month-old infants with diarrhea admitted to an urban hospital in Bangladesh.We prospectively enrolled all infants (n = 107) aged 0 to 6 months who were admitted to the Special Care Ward (SCW) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research Bangladesh (ICDDR,B) with diarrhea and pneumonia from September 2007 through December 2007.We compared the clinical features of pneumonia and hypoxemia of breast fed infants (n = 34) with those who were non-breast fed (n = 73).The median (inter-quartile range) duration of hypoxemia (hours) in non-breast-feds was longer than breast-fed infants [0.0 (0.0, 12.0) vs. 12.0 (0.0, 21.75); p = 0.021]. After adjusting for potential confounders such as inability to drink, fever, head nodding, cyanosis, grunting respiration, and lower chest wall in drawing, the non-breast-fed infants with pneumonia along with diarrhea had a higher probability of cough (OR 9.09; CI 1.34-61.71; p = 0.024), hypoxemia (OR 3.32; CI 1.23-8.93; p = 0.017), and severe undernutrition (OR 3.42; CI 1.29-9.12; p = 0.014).Non-breast feeding or cessation of breast feeding during the neonatal period may substantially increase the incidence of severe malnutrition, incidence of cough, and both the incidence and duration of hypoxemia in young infants presenting with pneumonia and diarrhea. The findings emphasize the paramount importance of the continuation of breast feeding in the neonatal period and early infancy

Metabolomic Analysis in Severe Childhood Pneumonia in The Gambia, West Africa: Findings from a Pilot Study

Pneumonia remains the leading cause of death in young children globally and improved diagnostics are needed to better identify cases and reduce case fatality. Metabolomics, a rapidly evolving field aimed at characterizing metabolites in biofluids, has the potential to improve diagnostics in a range of diseases. The objective of this pilot study is to apply metabolomic analysis to childhood pneumonia to explore its potential to improve pneumonia diagnosis in a high-burden setting. and Random Forests (RF). ‘Unsupervised’ (blinded) data were analyzed by Principal Component Analysis (PCA), while ‘supervised’ (unblinded) analysis was by Partial Least Squares-Discriminant Analysis (PLS-DA) and Orthogonal Projection to Latent Structures (OPLS). Potential markers were extracted from S-plots constructed following analysis with OPLS, and markers were chosen based on their contribution to the variation and correlation within the data set. The dataset was additionally analyzed with the machine-learning algorithm RF in order to address issues of model overfitting and markers were selected based on their variable importance ranking. Unsupervised PCA analysis revealed good separation of pneumonia and control groups, with even clearer separation of the groups with PLS-DA and OPLS analysis. Statistically significant differences (p<0.05) between groups were seen with the following metabolites: uric acid, hypoxanthine and glutamic acid were higher in plasma from cases, while L-tryptophan and adenosine-5′-diphosphate (ADP) were lower; uric acid and L-histidine were lower in urine from cases. The key limitation of this study is its small size.Metabolomic analysis clearly distinguished severe pneumonia patients from community controls. The metabolites identified are important for the host response to infection through antioxidant, inflammatory and antimicrobial pathways, and energy metabolism. Larger studies are needed to determine whether these findings are pneumonia-specific and to distinguish organism-specific responses. Metabolomics has considerable potential to improve diagnostics for childhood pneumonia

Neurological manifestations of SARS-CoV-2 infection in hospitalised children and adolescents in the UK: a prospective national cohort study

BACKGROUND: The spectrum of neurological and psychiatric complications associated with paediatric SARS-CoV-2 infection is poorly understood. We aimed to analyse the range and prevalence of these complications in hospitalised children and adolescents. METHODS: We did a prospective national cohort study in the UK using an online network of secure rapid-response notification portals established by the CoroNerve study group. Paediatric neurologists were invited to notify any children and adolescents (age <18 years) admitted to hospital with neurological or psychiatric disorders in whom they considered SARS-CoV-2 infection to be relevant to the presentation. Patients were excluded if they did not have a neurological consultation or neurological investigations or both, or did not meet the definition for confirmed SARS-CoV-2 infection (a positive PCR of respiratory or spinal fluid samples, serology for anti-SARS-CoV-2 IgG, or both), or the Royal College of Paediatrics and Child Health criteria for paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Individuals were classified as having either a primary neurological disorder associated with COVID-19 (COVID-19 neurology group) or PIMS-TS with neurological features (PIMS-TS neurology group). The denominator of all hospitalised children and adolescents with COVID-19 was collated from National Health Service England data. FINDINGS: Between April 2, 2020, and Feb 1, 2021, 52 cases were identified; in England, there were 51 cases among 1334 children and adolescents hospitalised with COVID-19, giving an estimated prevalence of 3·8 (95% CI 2·9-5·0) cases per 100 paediatric patients. 22 (42%) patients were female and 30 (58%) were male; the median age was 9 years (range 1-17). 36 (69%) patients were Black or Asian, 16 (31%) were White. 27 (52%) of 52 patients were classified into the COVID-19 neurology group and 25 (48%) were classified into the PIMS-TS neurology group. In the COVID-19 neurology group, diagnoses included status epilepticus (n=7), encephalitis (n=5), Guillain-Barré syndrome (n=5), acute demyelinating syndrome (n=3), chorea (n=2), psychosis (n=2), isolated encephalopathy (n=2), and transient ischaemic attack (n=1). The PIMS-TS neurology group more often had multiple features, which included encephalopathy (n=22 [88%]), peripheral nervous system involvement (n=10 [40%]), behavioural change (n=9 [36%]), and hallucinations at presentation (n=6 [24%]). Recognised neuroimmune disorders were more common in the COVID-19 neurology group than in the PIMS-TS neurology group (13 [48%] of 27 patients vs 1 [<1%] of 25 patients, p=0·0003). Compared with the COVID-19 neurology group, more patients in the PIMS-TS neurology group were admitted to intensive care (20 [80%] of 25 patients vs six [22%] of 27 patients, p=0·0001) and received immunomodulatory treatment (22 [88%] patients vs 12 [44%] patients, p=0·045). 17 (33%) patients (10 [37%] in the COVID-19 neurology group and 7 [28%] in the PIMS-TS neurology group) were discharged with disability; one (2%) died (who had stroke, in the PIMS-TS neurology group). INTERPRETATION: This study identified key differences between those with a primary neurological disorder versus those with PIMS-TS. Compared with patients with a primary neurological disorder, more patients with PIMS-TS needed intensive care, but outcomes were similar overall. Further studies should investigate underlying mechanisms for neurological involvement in COVID-19 and the longer-term outcomes. FUNDING: UK Research and Innovation, Medical Research Council, Wellcome Trust, National Institute for Health Research

Comparative Economic Evaluation of Haemophilus influenzae Type b Vaccination in Belarus and Uzbekistan

BACKGROUND: Hib vaccine has gradually been introduced into more and more countries during the past two decades, partly due to GAVI Alliance support to low-income countries. However, since Hib disease burden is difficult to establish in settings with limited diagnostic capacities and since the vaccine continues to be relatively expensive, some Governments remain doubtful about its value leading to concerns about financial sustainability. Similarly, several middle-income countries have not introduced the vaccine. The aim of this study is to estimate and compare the cost-effectiveness of Hib vaccination in a country relying on self-financing (Belarus) and a country eligible for GAVI Alliance support (Uzbekistan). METHODS AND FINDINGS: A decision analytic model was used to estimate morbidity and mortality from Hib meningitis, Hib pneumonia and other types of Hib disease with and without the vaccine. Treatment costs were attached to each disease event. Data on disease incidence, case fatality ratios and costs were primarily determined from national sources. For the Belarus 2009 birth cohort, Hib vaccine is estimated to prevent 467 invasive disease cases, 4 cases of meningitis sequelae, and 3 deaths, while in Uzbekistan 3,069 invasive cases, 34 sequelae cases and 341 deaths are prevented. Estimated costs per discounted DALY averted are US$9,323 in Belarus and US$ 267 in Uzbekistan. CONCLUSION: The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden. Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus. However, when seen in the context of the relative ability to pay for public health, the vaccine can be considered cost-effective in both countries

Pneumonia and poverty: a prospective population-based study among children in Brazil

<p>Abstract</p> <p>Background</p> <p>Children in developing country suffer the highest burden of pneumonia. However, few studies have evaluated associations between poverty and pneumonia.</p> <p>Methods</p> <p>A prospective population-based study on pneumonia was carried out as part of the Latin America Epidemiological Assessment of Pneumococcus (LEAP study). Chest x-rays were obtained for children one to 35 months old with suspected pneumonia presenting to emergency care centers and hospital emergency rooms in Goiania, Brazil. Chest radiographs were evaluated according to WHO guidelines. Clustering of radiologically-confirmed pneumonia were evaluated using a Poisson-based spatial scan statistic. Associations between census socioeconomic indicators and pneumonia incidence rates were analyzed using generalized linear models.</p> <p>Results</p> <p>From May, 2007 to May, 2009, chest radiographs were obtained from 11 521 children with clinical pneumonia; 3955 episodes were classified as radiologically-confirmed. Incidence rates were significantly higher in very low income areas (4825.2 per 10⁵) compared to high income areas (1637.3 per 10⁵). Spatial analysis identified clustering of confirmed pneumonia in Western (RR 1.78; p = 0.001) and Southeast (RR 1.46; p = 0.001) regions of the city, and clustering of hospitalized pneumonia in the Western region (RR 1.69; p = 0.001). Lower income households and illiteracy were associated with pneumonia incidence.</p> <p>Conclusions</p> <p>In infants the risk of developing pneumonia is inversely associated with the head of household income and with the woman educational level. Areas with deprived socioeconomic conditions had higher incidence of pneumonia and should be targeted for high vaccination coverage.</p