Specific Viruses Detected in Nigerian Children in Association with Acute Respiratory Disease

Occurrence of different viruses in acute respiratory tract infections of Nigerian children was examined. Respiratory swabs were collected from 246 children referred to hospital clinics because of acute respiratory symptoms from February through May 2009. Validated real-time RT-PCR techniques revealed nucleic acids of at least one virus group in 189 specimens (77%). Human rhinoviruses and parainfluenza viruses were present each in one third of the children. Adenoviruses, enteroviruses, human metapneumovirus, human bocavirus, and influenza C virus were also relatively common. Possibly due to their seasonal occurrence, influenza A and B virus, and respiratory syncytial virus were detected rarely. We conclude that all major groups of respiratory tract viruses are causing illness in Nigerian children

Predictors of human-infective RNA virus discovery in the United States, China, and Africa, an ecological study

BACKGROUND: The variation in the pathogen type as well as the spatial heterogeneity of predictors make the generality of any associations with pathogen discovery debatable. Our previous work confirmed that the association of a group of predictors differed across different types of RNA viruses, yet there have been no previous comparisons of the specific predictors for RNA virus discovery in different regions. The aim of the current study was to close the gap by investigating whether predictors of discovery rates within three regions—the United States, China, and Africa—differ from one another and from those at the global level. METHODS: Based on a comprehensive list of human-infective RNA viruses, we collated published data on first discovery of each species in each region. We used a Poisson boosted regression tree (BRT) model to examine the relationship between virus discovery and 33 predictors representing climate, socio-economics, land use, and biodiversity across each region separately. The discovery probability in three regions in 2010–2019 was mapped using the fitted models and historical predictors. RESULTS: The numbers of human-infective virus species discovered in the United States, China, and Africa up to 2019 were 95, 80, and 107 respectively, with China lagging behind the other two regions. In each region, discoveries were clustered in hotspots. BRT modelling suggested that in all three regions RNA virus discovery was better predicted by land use and socio-economic variables than climatic variables and biodiversity, although the relative importance of these predictors varied by region. Map of virus discovery probability in 2010–2019 indicated several new hotspots outside historical high-risk areas. Most new virus species since 2010 in each region (6/6 in the United States, 19/19 in China, 12/19 in Africa) were discovered in high-risk areas as predicted by our model. CONCLUSIONS: The drivers of spatiotemporal variation in virus discovery rates vary in different regions of the world. Within regions virus discovery is driven mainly by land-use and socio-economic variables; climate and biodiversity variables are consistently less important predictors than at a global scale. Potential new discovery hotspots in 2010–2019 are identified. Results from the study could guide active surveillance for new human-infective viruses in local high-risk areas. FUNDING: FFZ is funded by the Darwin Trust of Edinburgh (https://darwintrust.bio.ed.ac.uk/). MEJW has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 874735 (VEO) (https://www.veo-europe.eu/)

Outpatient antibiotic use in acute respiratory infections in Ho Chi Minh City, Vietnam

Acute respiratory infections (ART) are among the most frequent infectious diseases in children worldwide, particularly in developing countries. Antibiotics are very often prescribed or purchased without prescription for the treatment of ARl, although viruses are recognised as the predominant pathogens [1-7]. The aim of the work presented in this thesis was to quantify antibiotic use in outpatients with ARI in Children's Hospital 1, Ho Chi Minh City, Vietnam, to identify the viral and bacterial respiratory aetiologic agents and to assess the impact of antibiotic use on the selection of resistant bacteria in the intestinal flora. Two prospective descriptive studies were conducted in the outpatient clinic: one in ARl patients and the other in healthy children. The epidemiology, presentation and treatment characteristics of children with ARI in the outpatient clinic were described. Antibiotics were prescribed in 99.6% of 563 patients while respiratory viruses were detected in 72.5% among these patients with the use of multiplex PCR in respiratory specimens. Antibiotic use was considered inappropriate in 67.7% of cases, according to evidence-based guidelines and detected pathogens. Besides antibiotics, other treatments such as oral bronchodilators, oral corticosteroids, antihistamines, and mucolytic agents were commonly used at the rates of 57.6%, 10.3%, 11 % and 11 %, respectively, and in most of the cases, were not in accordance with the current guidelines. We observed a short-term selection of resistant Enterobacteriaceae in patients' intestinal flora resistant not only to the antibiotic class the patients received but also co-selection of resistance to other rarely used antibiotics. HPLC assays were developed with high sensitivity and specificity to determine the presence of 6 beta- lactam antibiotics in the urine antibiotic use before presentation as determined by HPLC (32%) was significantly higher than that reported by parent interviews (21 %). Antibiotic use in Vietnam is largely unrestricted leading to overuse and overprescription for uncomplicated ARI

Predicción del riesgo de infección bacteriana grave en niños con enfermedad de células falciformes

Los niños con enfermedad de células falciformes (ECF) tienen un riesgo aumentado de infección bacteriana grave (IBG), principalmente debido a la asplenia funcional que presentan. Sin embargo, en las últimas décadas, la incidencia de estas infecciones ha disminuido en estos pacientes, gracias a la instauración de medidas preventivas como la profilaxis antibiótica con penicilina y la vacunación. A pesar de ello, debido a su potencial riesgo, cuando estos pacientes presentan fiebre suelen recibir tratamiento antibiótico de amplio espectro, en muchas ocasiones con ingreso hospitalario. Se han descrito algunos parámetros, tanto clínicos como de laboratorio, como marcadores de IBG en estos pacientes, con distintos resultados. Sin embargo, hasta el momento, ninguno de ellos ha conseguido diferenciar de forma segura la etiología de la fiebre en estos niños. Las citoquinas proinflamatorias han sido estudiadas en pacientes con ECF en situación basal y con crisis vasooclusivas, pero no han sido estudiadas en casos de infección..

Epidemiology of respiratory syncytial virus associated acute lower respiratory infection in young children

Introduction Acute lower respiratory infection (ALRI) remains as a leading cause of childhood morbidity and mortality. With the continued universal vaccination campaign against bacterial pathogens, an increase in relative proportion of respiratory viruses contributing to ALRI is anticipated. Respiratory syncytial virus (RSV) has been recognised as the most common pathogen identified in young children presenting with ALRI as well as an important cause of hospital admission. This thesis aims to estimate the aetiological roles and attributable fractions of common respiratory viruses among ALRI cases and investigate the risk factors for RSV associated ALRI in young children. It also aims to estimate the global and regional incidence of RSV associated ALRI in both community and hospital based settings, and the possible boundaries for RSV associated ALRI mortality in children younger than five years old. Methods Systematic reviews were carried out separately for the following three research questions: aetiological roles of RSV and other common viruses in ALRI cases, risk factors for RSV associated ALRI and global/regional burden of RSV associated ALRI, formulating an overall picture of epidemiology of RSV associated ALRI in young children. They all focused on children younger than five years old. The identified studies were selected according to pre-defined inclusion and exclusion criteria. The whole process was conducted following the PRISMA guidelines for systematic review and meta-analysis. Unpublished data from RSV Global Estimates Network (RSV GEN) were collected from 45 leading researchers on paediatric pneumonia (primarily in developing countries). They either reanalysed data from their already published work with the pre-defined standardised case definitions or shared hitherto unpublished data from ongoing studies. Data from both systematic reviews and RSV GEN working group were included into further meta-analysis. Random effects model was consistently applied in all meta-analyses. Results There were 23 studies identified through literature search satisfying the eligibility criteria, investigated the viral aetiology of ALRI in young children. Strong evidence was observed for RSV in support of its causal contribution in children presenting with ALRI and the association was significant measured in odds ratio: 9.79 (4.98-19.27). Thus, the corresponding attributable fraction among the exposed was estimated as 90% (80%-95%), which means around 90% of RSV associated ALRI cases were in fact attributed to RSV in a causal path. In total, 27 studies (including 4 unpublished studies) were included and contributed to the analysis. Across these studies, 18 risk factors were described and 8 of them were observed to have significant associations with RSV infection: prematurity - gestational age <37 weeks, low birth weight (<2.5 kg), being male, having siblings, maternal smoking, history of atopy, no breastfeeding and crowding - >7 persons in household. Overall, 304 studies met the selection criteria and were included to estimate the global and regional burden of RSV associated ALRI in young children. These included 73 published articles identified through Chinese language databases and 76 unpublished studies provided by RSV GEN working group, mainly from developing countries. It is estimated that in 2015, there were 33.0 (95% CI 20.6-53.2) million episodes of RSV associated ALRI occurring in children younger than 5 years old across the world. 30.5 (95% CI 19.5-47.9) million of them were in developing countries. 3.0 (95% CI 2.2-4.0) million cases were severe enough and warranted hospitalisation. Around 60,000 children died in the hospital settings with 99% of these deaths occurring in developing countries. The overall mortality from RSV associated ALRI was estimated about 131,000. Conclusion This thesis not only enhanced the epidemiological understanding of RSV in young children, but also provided important information for public health decision makers. It incorporated both data through systematic reviews of published articles in the past 20 years and more than 70 unpublished data sets shared by RSV GEN working group. The population based incidence, hospitalisation, mortality and risk factor data are essential to assess the various severity of illness in a specific age group and region, and inform local public health professionals regarding appropriate and prompt cases management, prevention and vaccine allocation strategies. National sentinel systems of RSV surveillance gathering structured and reasonably representative data are needed. Within the surveillance system, a universal definition regarding disease severity in various settings should be developed, and diagnostic methods with higher sensitivity and specificity should be applied

Emerg Infect Dis

PMC4550154611

Epidemiology of emerging human-infective RNA viruses: discovery, geographical extent, and disappearance

Previous investigations into human infectious diseases have revealed RNA viruses as major etiological agents. Given the recent rate of newly detected human-infective RNA viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, Middle East respiratory syndrome coronavirus, and Bundibugyo ebolavirus, targeting virus discovery in high-risk regions, characterizing viruses with the greatest likelihood of spreading and establishing sustained infection in humans would benefit better preparedness for future outbreaks. There is a lack of evidence on determinants of spatio-temporal patterns in the discovery of human-infective RNA viruses, though previous studies have attempted to identify hotspots of emerging infectious diseases caused by various pathogens. There are also no quantitative studies exploring predictors of geographical extent and the disappearance for all currently known human-infective RNA viruses. This thesis aimed to address the following gaps. 1. Identifying predictors discriminating between areas with and without discovery of human-infective RNA viruses and predicting discovery hotspots, at both global and regional scales. Predictors identified include socio-economic, climatic, land use, and biodiversity variables. 2. Prediction of the geographical extent and the disappearance of human-infective RNA viruses, using features such as taxonomy, virus structure, transmission mode, host range, origin, and clinical presentation. 3. Taking SARS-CoV-2 as an example, investigating how predictors related to demographics, socioeconomics, travel, healthcare, co-morbidities, readiness, geography, COVID-19 testing, and interventions have affected the epidemic of the disease it caused—coronavirus disease 2019 (COVID-19)—between countries in the WHO African Region. In order to address the gaps outlined above, I firstly geocoded the first reports of 223 human-infective RNA viruses at the global scale. Using a Poisson boosted regression tree (BRT) model, I identified GDP growth, GDP, and urbanization as top predictors of virus discovery, and predicted discovery hotspots including both historical hotspots—eastern North America, Europe, central Africa, eastern Australia, and north-eastern South America, and new hotspots—East and Southeast Asia, India, and Central America. Stratified analyses suggested discovery of vector-borne viruses and strictly zoonotic viruses was more correlated with climatic variables and biodiversity, whereas the discovery of non-vector-borne viruses and human-transmissible viruses was more strongly correlated with GDP and urbanization. Next, I focused on comparisons of the specific predictors of RNA virus discovery in three different regions with different GDP—United States, China, and Africa. A similar methodology as the global analysis was used on each region separately, the results showed that predictors such as GDP and land use continued to be top predictors in three regions, but climate and biodiversity variables were consistently less important predictors than at a global scale. To identify predictors of the geographical extent and the disappearance (no record of infection in the literature for the past ten years or more), I collated information for 223 human-infective RNA viruses on their geographical extents and persistence in causing human infections from peer-reviewed literature. By fitting Bernoulli BRT models, I observed that viral features that predicted wide geographic extent included transmissibility between humans, a +ssRNA genome, narrow host range [i.e. infecting humans only or humans and other non-human primates (NHP) only], and having a reservoir host in a NHP. Viruses were more likely to disappear if they were incapable of transmission between humans, have had a localised geographic extent, a dsRNA genome, were non-pathogenic and non-fatal, were firstly discovered through active discovery programmes rather than passive investigation of the aetiology, and were transmitted by vectors and direct contact. Results for both geographical extent and virus disappearance did not change after factoring out reporting effort. I concluded that multiple characteristics determined the geographical extent and disappearance of human-infective RNA viruses; however, transmission mode and structure were consistently the most important predictors of the geographical extent and disappearance of human-infective RNA viruses. Host range was an important predictor of geographical extent, though less important for disappearance. Geographical extent, clinical presentation and discovery process all contributed to the probability of a virus disappearing. To understand the differences between epidemics of COVID-19 between countries of the WHO African Region, I selected the timing of the first case and the mortality rate in the first and second waves as the three outcomes. By applying a series of statistical models including Cox proportional hazards regression models, generalized linear mixed models and multinomial logistic regression models, I found that COVID-19 in Africa arrived earlier and caused greater mortality in countries with more pre-pandemic international connectivity and a more urban population. Mortality was exacerbated by high HIV prevalence. The stringency and timing of government restrictions on behaviour were not associated with a lower per capita mortality rate. A more urban population and a higher infectious disease resilience score were associated with more stringent restrictions and/or a higher per capita mortality rate. The predictor set for the first and second waves were similar, and first wave per capita mortality was a significant predictor of second wave per capita mortality. In summary, studies in this thesis showed that there were variations in predictors of discovery both between virus types and geographical regions, and identified high-risk regions for virus discovery beyond their historical extent. The studies also provided proof-of-principle for the prediction of attributes such as mortality, geographical extent, and disappearance for new human-infective RNA viruses. These results help identify priority regions for investment in surveillance systems for new human-infective viruses, and to make risk assessments once they have emerged

Emerging infectious diseases

Emerging Infectious Diseases is providing access to these abstracts on behalf of the ICEID 2012 program committee (www.iceid.org), which performed peer review. Emerging Infectious Diseases has not edited or proofread these materials and is not responsible for inaccuracies or omissions. All information is subject to change. Comments and corrections should be brought to the attention of the authors.Influenza preparedness: lessons learned -- Policy implications and infectious diseases -- Improving preparedness for infectious diseases -- New or rapid diagnostics -- Foodborne and waterborne infections -- Effective and sustainable surveillance platforms -- Healthcare-associated infections -- Molecular epidemiology -- Antimicrobial resistance -- Tropical infections and parasitic diseases -- H1N1 influenza -- Risk Assessment -- Laboratory Support -- Zoonotic and Animal Diseases -- Viral Hepatitis -- E1. Zoonotic and animal diseases -- E2. Vaccine issues -- E3. H1N1 influenza -- E4. Novel surveillance systems -- E5. Antimicrobial resistance -- E6. Late-breakers I -- Antimicrobial resistance -- Influenza preparedness: lessons learned -- Zoonotic and animal diseases -- Improving preparedness for infectious diseases -- Laboratory support -- Early warning systems -- H1N1 influenza -- Policy implications and infectious diseases -- Modeling -- Molecular epidemiology -- Novel surveillance systems -- Tropical infections and parasitic diseases -- Strengthening public health systems -- Immigrant and refugee health -- Foodborne and waterborne infections -- Healthcare-associated infections -- Foodborne and waterborne infections -- New or rapid diagnostics -- Improving global health equity for infectious diseases -- Vulnerable populations -- Novel agents of public health importance -- Influenza preparedness: lessons learned -- Molecular epidemiology -- Zoonotic and animal diseases -- Vaccine-preventable diseases -- Outbreak investigation: lab and epi response -- H1N1 influenza -- laboratory support -- effective and sustainable surveillance platforms -- new vaccines -- vector-borne diseases and climate change -- travelers' health -- J1. Vectorborne diseases and climate change -- J2. Policy implications and infectious diseases -- J3. Influenza preparedness: lessons learned -- J4. Effective and sustainable surveillance platforms -- J5. Outbreak investigation: lab and epi response I -- J6. Late-breakers II -- Strengthening public health systems -- Bacterial/viral coinfections -- H1N1 influenza -- Novel agents of public health importance -- Foodborne and waterborne infections -- New challenges for old vaccines -- Vectorborne diseases and climate change -- Novel surveillance systems -- Geographic information systems (GIS) -- Improving global health equity for infectious diseases -- Vaccine preventable diseases -- Vulnerable populations -- Laboratory support -- Prevention challenges for respiratory diseases -- Zoonotic and animal diseases -- Outbreak investigation: lab and epi response -- Vectorborne diseases and climate change -- Outbreak investigation: lab and epi response -- Laboratory proficiency testing/quality assurance -- Effective and sustainable surveillance platforms -- Sexually transmitted diseases -- H1N1 influenza -- Surveillance of vaccine-preventable diseases -- Foodborne and waterborne infections -- Role of health communication -- Emerging opportunistic infections -- Host and microbial genetics -- Respiratory infections in special populations -- Zoonotic and animal diseases -- Laboratory support -- Antimicrobial resistance -- Vulnerable populations -- Global vaccine initiatives -- Tuberculosis -- Prevention challenges for respiratory diseases -- Infectious causes of chronic diseases -- O1. Outbreak investigation: lab and epi response II -- O2. Prevention challenges for respiratory diseases -- O3. Populations at high risk for infectious diseases -- O4. Foodborne and waterborne infections -- O5. Laboratory support: surveillance and monitoring infections -- O6. Late-breakers IIIAbstracts published in advance of the conference

Community-acquired pneumonia in Malawian adults: Aetiology and predictors of mortality.

Background Community-acquired pneumonia (CAP) is one of the commonest causes of adult hospitalisation in sub-Saharan Africa, but recent data describing its epidemiology, microbial aetiology and outcome are limited. Focusing particularly on Malawi, the overall aim of this thesis was to describe the aetiology and outcome of CAP in sub-Saharan African to determine the key predictors of mortality. Methods Firstly, a systematic review of studies of CAP in adults in sub-Saharan Africa was performed to describe CAP aetiology, estimate the mortality rate and identify risk factors associated with death. Secondly, a prospective observational study of adults hospitalised with clinically diagnosed CAP to Queen Elizabeth Central Hospital, Blantyre, Malawi was completed to describe microbial aetiology using modern diagnostic modalities, determine outcome and identify prognostics factors. Thirdly, having identified in preliminary analyses of the prospective cohort that hypoxaemia was an independent risk factor for mortality, a study of the effectiveness of supplemental oxygen delivery by oxygen concentrator to correct hypoxaemia in adults with suspected CAP was performed. Results In both the systematic review and the prospective cohort the predominant burden of hospitalised CAP was in young (average age 38 and 35, respectively) and HIV-positive (52% and 78%) patients with limited chronic cardiovascular and pulmonary comorbidity. Streptococcus pneumoniae (27% and 21%) and Mycobacterium tuberculosis (19% and 23%) were the most commonly identified causes. The overall mortality rate for hospitalised patients in the systematic review was 9.5%, but data describing prognostic factors were limited. In the prospective cohort (n=459), death by day 30 occurred in 14.6% and was associated with: male sex (aOR 2.57); pre-presentation symptom duration (aOR 1.11 per day increase); inability to stand (aOR 4.28); heart rate (aOR 1.02 per beat/minute rise); oxygen saturations (aOR 0.95 per % rise); white cell count (aOR 0.91 per 109/L rise); haemoglobin (aOR 0.90 per g/dL rise). A newly derived four parameter mortality risk prediction tool based on male sex, oxygen saturations <90%, inability to stand and heart rate ≥125 /min predicted 30-day mortality with reasonable accuracy (area under the receiver-operating curve (AUROC) 0.79) whilst existing tools performed poorly (CURB65: AUROC 0.60; SMRT-CO: AUROC 0.66). Hypoxaemia was corrected in 86.4% (n=59) of adults with suspected CAP with supplemental oxygen at standard flow-rate of 5 litres/minute. Failure to attain normoxaemia was associated with a more than four-fold increase in the risk of death (RR 4.25). Conclusions The major burden of hospitalised CAP in low-resource, sub-Saharan African settings is seen in young and HIV-positive adults, many of whom have TB. Extrapolating CAP assessment and treatment algorithms from well-resourced settings where the epidemiology and aetiology of disease is very different is flawed. If validated, locally derived severity assessment tools may provide a rational basis on which to stratify CAP management. Strategies to increase early detection and treatment of TB and to improve supportive care, in particular the correction of hypoxaemia, hold considerable promise for improving CAP outcomes and should be evaluated in clinical trials