Human enterovirus 68 (EV-D68) is a historically rarely reported virus linked with respiratory disease. In the past 3 years, a large increase in respiratory disease associated with EV-D68 has been ...reported, with documented outbreaks in North America, Europe and Asia. In several outbreaks, genetic differences were identified among the circulating strains, indicating the presence of multiple clades. In this report, we analyse archived and novel EV-D68 strains from Africa and the USA, obtained from patients with respiratory illness. Phylogenetic analysis of all EV-D68 sequences indicates that, over the past two decades, multiple clades of the virus have emerged and spread rapidly worldwide. All clades appear to be currently circulating and contributing to respiratory disease.
To determine paediatric blood sample volume limits that are consistent with physiological "minimal risk."
A literature review was performed to search for evidence concerning the adverse effects of ...blood sampling in children and for guidelines on sampling volume in paediatric research. The search included Medline, EMBASE, other web-based and non-web-based sources and the bibliographies of the sources identified. Experts were also consulted.
Five studies and nine guidelines were identified. Existing guidelines specify paediatric blood sample volume limits ranging from 1% to 5% of total blood volume (TBV) over 24 hours and up to 10% of TBV over 8 weeks. The evidence available is limited and includes findings from non-randomized studies showing a minimal risk with one-off sampling of up to 5% of TBV.
The evidence available is consistent with the conclusion that all identified guidelines are within the limits of "minimal risk." However, more and better evidence is required to draw firmer conclusions. Researchers and institutional review boards need to take into account the total sampling volume needed for both clinical care and research rather than for each alone. The child's general state of health should be considered and extra caution should be observed particularly with children whose illness can deplete blood volume or haemoglobin or hinder their replenishment. Local policies must also address the appropriateness and local acceptability of collection procedures and of the blood volumes drawn.
In response, WHO's Integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea has set targets and a framework for tackling this challenge, an important component being to ...measure progress.1 In The Lancet Infectious Diseases, the Global Burden of Disease (GBD) 2016 Lower Respiratory Infections Collaborators provide further estimates of the morbidity and mortality from lower respiratory infections, principally pneumonia and bronchiolitis.2 They also provide estimates for lower respiratory infections caused by four microorganisms—Streptococcus pneumoniae, Haemophilus influenzae type b, influenza, and respiratory syncytial virus. According to the models presented, S pneumoniae was the leading cause of lower respiratory infection morbidity and mortality globally, contributing to more than 1 million deaths, more than the other three aetiologies combined. Interventions to enhance access to health care are needed to augment preventive measures. ...a greater understanding is needed of the role of individual respiratory pathogens (more than just the four included in this study), to provide more accurate estimates of disease burden and to better target interventions.
The Pneumonia Etiology Research for Child Health (PERCH) project is a 7-country, standardized, comprehensive evaluation of the etiologic agents causing severe pneumonia in children from developing ...countries. During previous etiology studies, between one-quarter and one-third of patients failed to yield an obvious etiology; PERCH will employ and evaluate previously unavailable innovative, more sensitive diagnostic techniques. Innovative and rigorous epidemiologic and analytic methods will be used to establish the causal association between presence of potential pathogens and pneumonia. By strategic selection of study sites that are broadly representative of regions with the greatest burden of childhood pneumonia, PERCH aims to provide data that reflect the epidemiologic situation in developing countries in 2015, using pneumococcal and Haemophilus influenzae type b vaccines. PERCH will also address differences in host, environmental, and/or geographic factors that might determine pneumonia etiology and, by preserving specimens, will generate a resource for future research and pathogen discovery.
The death of a mother is a tragedy in itself but it can also have devastating effects for the survival of her children. We aim to explore the impact of a mother's death on child survival in rural ...Gambia, West Africa.
We used 25 years of prospective surveillance data from the Farafenni Health and Demographic surveillance system (FHDSS). Mortality rates per 1,000 child-years up to ten years of age were estimated and Kaplan-Meier survival curves plotted by maternal vital status. Cox proportional hazard models were used to examine factors associated with child survival.
Between 1st April 1989 and 31st December 2014, a total of 2, 221 (7.8%) deaths occurred during 152,906 child-years of follow up. Overall mortality rate was 14.53 per 1,000 child-years (95% CI: 13.93-15.14). Amongst those whose mother died, the rate was 25.89 (95% CI: 17.99-37.25) compared to 14.44 (95% CI: 13.84-15.06) per 1,000 child-years for those whose mother did not die. Children were 4.66 (95% CI: 3.15-6.89) times more likely to die if their mother died compared to those with a surviving mother. Infants whose mothers died during delivery or shortly after were up to 7 times more likely to die within the first month of life compared to those whose mothers survived. Maternal vital status was significantly associated with the risk of dying within the first 2 years of life (p-value <0.05), while this was no longer observed for children over 2 years of age (P = 0.872). Other factors associated with an increased risk of dying were living in more rural areas, and birth spacing and year of birth.
Mother's survival is strongly associated with child survival. Our findings highlight the importance of the continuum of care for both the mother and child not only throughout pregnancy, and childbirth but beyond 6 weeks post-partum.
The global burden of pediatric severe respiratory illness is substantial, and influenza viruses contribute to this burden. Systematic surveillance and testing for influenza among hospitalized ...children has expanded globally over the past decade. However, only a fraction of the data has been used to estimate influenza burden. In this analysis, we use surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide.
We aggregated data from a systematic review (n = 108) and surveillance platforms (n = 37) to calculate a pooled estimate of the proportion of samples collected from children hospitalized with respiratory illnesses and positive for influenza by age group (<6 mo, <1 y, <2 y, <5 y, 5-17 y, and <18 y). We applied this proportion to global estimates of acute lower respiratory infection hospitalizations among children aged <1 y and <5 y, to obtain the number and per capita rate of influenza-associated hospitalizations by geographic region and socio-economic status. Influenza was associated with 10% (95% CI 8%-11%) of respiratory hospitalizations in children <18 y worldwide, ranging from 5% (95% CI 3%-7%) among children <6 mo to 16% (95% CI 14%-20%) among children 5-17 y. On average, we estimated that influenza results in approximately 374,000 (95% CI 264,000 to 539,000) hospitalizations in children <1 y-of which 228,000 (95% CI 150,000 to 344,000) occur in children <6 mo-and 870,000 (95% CI 610,000 to 1,237,000) hospitalizations in children <5 y annually. Influenza-associated hospitalization rates were more than three times higher in developing countries than in industrialized countries (150/100,000 children/year versus 48/100,000). However, differences in hospitalization practices between settings are an important limitation in interpreting these findings.
Influenza is an important contributor to respiratory hospitalizations among young children worldwide. Increasing influenza vaccination coverage among young children and pregnant women could reduce this burden and protect infants <6 mo.
Background. Pneumonia is the leading cause of death in children globally. Clinical algorithms remain suboptimal for distinguishing severe pneumonia from other causes of respiratory distress such as ...malaria or distinguishing bacterial pneumonia and pneumonia from others causes, such as viruses. Molecular tools could improve diagnosis and management. Methods. We conducted a mass spectrometry–based proteomic study to identify and validate markers of severity in 390 Gambian children with pneumonia (n = 204) and age-, sex-, and neighborhood-matched controls (n = 186). Independent validation was conducted in 293 Kenyan children with respiratory distress (238 with pneumonia, 41 with Plasmodium falciparum malaria, and 14 with both). Predictive value was estimated by the area under the receiver operating characteristic curve (AUC). Results. Lipocalin 2 (Lpc-2) was the best protein biomarker of severe pneumonia (AUC, 0.71 95% confidence interval, .64–.79) and highly predictive of bacteremia (78% 64%–92%), pneumococcal bacteremia (84% 71%–98%), and "probable bacterial etiology" (91% 84%—98%). These results were validated in Kenyan children with severe malaria and respiratory distress who also met the World Health Organization definition of pneumonia. The combination of Lpc-2 and haptoglobin distinguished bacterial versus malaria origin of respiratory distress with high sensitivity and specificity in Gambian children (AUC, 99% 95% confidence interval, 99%–100%) and Kenyan children (82% 74%–91%). Conclusions. Lpc-2 and haptoglobin can help discriminate the etiology of clinically defined pneumonia and could be used to improve clinical management. These biomarkers should be further evaluated in prospective clinical studies.
To evaluate the coverage and timeliness of the Expanded Programme on Immunisation (EPI) in The Gambia.
Vaccination data were obtained between January 2005 and December 2012 from the Farafenni Health ...and Demographic Surveillance System (FHDSS), the Basse Health and Demographic Surveillance System (BHDSS), the Kiang West Demographic surveillance system (KWDSS), a cluster survey in the more urban Western Health Region (WR) and a cross sectional study in four clinics in the semi-urban Greater Banjul area of WR. Kaplan-Meier survival function was used to estimate the proportion vaccinated by age and to assess timeliness to vaccination.
BCG vaccine uptake was over 95% in all regions. Coverage of DPT1 ranged from 93.2% in BHDSS to 99.8% in the WR. Coverage decreased with increasing number of DPT doses; DPT3 coverage ranged from 81.7% in BHDSS to 99.0% in WR. Measles vaccination coverage ranged from 83.3% in BHDSS to 97.0% in WR. DPT4 booster coverage was low and ranged from 43.9% in the WR to 82.8% in KWDSS. Across all regions, delaying on previous vaccinations increased the likelihood of being delayed for the subsequent vaccination.
The Gambia health system achieves high vaccine coverage in the first year of life. However, there continues to be a delay to vaccination which may impact on the introduction of new vaccines. Examples of effectively functioning EPI programmes such as The Gambia one may well be important models for other low income countries struggling to achieve high routine vaccination coverage.
Introduction of pneumococcal conjugate vaccines (PCVs) of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by ...serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural Gambia.
A cluster-randomized (by village) trial of the impact of PCV-7 on pneumococcal nasopharyngeal carriage was conducted in 21 Gambian villages between December 2003 to June 2008 (5,441 inhabitants in 2006). Analysis was complemented with data obtained before vaccination. Because efficacy of PCV-9 in young Gambian children had been shown, it was considered unethical not to give PCV-7 to young children in all of the study villages. PCV-7 was given to children below 30 mo of age and to those born during the trial in all study villages. Villages were randomized (older children and adults) to receive one dose of PCV-7 (11 vaccinated villages) or meningococcal serogroup C conjugate vaccine (10 control villages). Cross-sectional surveys (CSSs) to collect nasopharyngeal swabs were conducted before vaccination (2,094 samples in the baseline CSS), and 4-6, 12, and 22 mo after vaccination (1,168, 1,210, and 446 samples in CSS-1, -2, and -3, respectively). A time trend analysis showed a marked fall in the prevalence of vaccine-type pneumococcal carriage in all age groups following vaccination (from 23.7% and 26.8% in the baseline CSS to 7.1% and 8.5% in CSS-1, in vaccinated and control villages, respectively). The prevalence of vaccine-type pneumococcal carriage was lower in vaccinated than in control villages among older children (5 y to <15 y of age) and adults (≥15 y of age) at CSS-2 (odds ratio OR = 0.15 95% CI 0.04-0.57 and OR = 0.32 95% CI 0.10-0.98, respectively) and at CSS-3 (OR = 0.37 95% CI 0.15-0.90 for older children, and 0% versus 7.6% for adults in vaccinated and control villages, respectively). Differences in the prevalence of non-vaccine-type pneumococcal carriage between vaccinated and control villages were small.
Vaccination of Gambian children reduced vaccine-type pneumococcal carriage across all age groups, indicating a "herd effect" in non-vaccinated older children and adults. No significant serotype replacement was detected. Please see later in the article for the Editors' Summary.
Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus ...pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae.
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