Long-term morbidity from severe pneumonia in early childhood in The Gambia, West Africa: a follow-up study

OBJECTIVE: To assess long-term outcomes in severe early childhood pneumonia in The Gambia. DESIGN: Observational cohort study of children hospitalised with severe pneumonia between 1992 and 1 04 compared to age, sex, and neigh bourhood-marched controls on measures of current general and pulmonary health. RESULTS: Of 83 children successfully traced, 68 of the 69 alive at follow-up agreed to participate. Thirteen per Cent of cases and 4% of controls had lung disease clinically or on spirometry. Another 16 (13%) participants had abnormal spirometry but did not meet the American Thoracic Society technical criteria (formally 'inconclusive'). Odds ratios of lung disease among childhood pneumonia cases were 2.93 (95 %CI 0.69-12.48, P = 0.1468) with incon-clusives omitted; 2.53 (95 %CI 0.61-10.59, P = 0.2033) with inconclusives included as normal; and 2.83 (95%CI 1.09-7.36, P = 0.0334) with inconclusives included as lung disease. Among deceased cases, most deaths were reported within weeks of discharge, suggesting a possible connection between admission and subsequent death. CONCLUSION: These African data, while not conclusive, add to previous data suggesting a link between severe early, childhood pneumonia and later chronic lung disease. While larger-scale research is needed, increased awareness of possible long-term morbidity in children with severe pneumonia is warranted to limit its impact and optimise long-term health

Impact of routine vaccination against Haemophilus influenzae type b in The Gambia: 20 years after its introduction

Background: In 1997, The Gambia introduced three primary doses of Haemophilus influenzae type b (Hib) conjugate vaccine without a booster in its infant immunisation programme along with establishment of a population-based surveillance on Hib meningitis in the West Coast Region (WCR). This surveillance was stopped in 2002 with reported elimination of Hib disease. This was re-established in 2008 but stopped again in 2010. We aimed to re-establish the surveillance in WCR and to continue surveillance in Basse Health and Demographic Surveillance System (BHDSS) in the east of the country to assess any shifts in the epidemiology of Hib disease in The Gambia. Methods: In WCR, population-based surveillance for Hib meningitis was re-established in children aged under-10 years from 24 December 2014 to 31 March 2017, using conventional microbiology and Real Time Polymerase Chain Reaction (RT-PCR). In BHDSS, population-based surveillance for Hib disease was conducted in children aged 2-59 months from 12 May 2008 to 31 December 2017 using conventional microbiology only. Hib carriage survey was carried out in pre-school and school children from July 2015 to November 2016. Results: In WCR, five Hib meningitis cases were detected using conventional microbiology while another 14 were detected by RT-PCR. Of the 19 cases, two (11%) were too young to be protected by vaccination while seven (37%) were unvaccinated. Using conventional microbiology, the incidence of Hib meningitis per 100 000-child-year (CY) in children aged 1-59 months was 0.7 in 2015 (95% confidence interval (CI) = 0.0-3.7) and 2.7 (95% CI = 0.7-7.0) in 2016. In BHDSS, 25 Hib cases were reported. Nine (36%) were too young to be protected by vaccination and five (20%) were under-vaccinated for age. Disease incidence peaked in 2012-2013 at 15 per 100 000 CY and fell to 5-8 per 100 000 CY over the subsequent four years. The prevalence of Hib carriage was 0.12% in WCR and 0.38% in BHDSS. Conclusions: After 20 years of using three primary doses of Hib vaccine without a booster Hib transmission continues in The Gambia, albeit at low rates. Improved coverage and timeliness of vaccination are of high priority for Hib disease in settings like Gambia, and there are currently no clear indications of a need for a booster dose

Pneumonia

Pneumonia is an important cause of morbidity and mortality globally. It is the leading cause of death in infants and young children with the majority of these deaths occurring in low income countries. Risk factors affecting incidence and outcome include extremes of age, poor nutrition, immunosuppression, environmental exposures and socioeconomic determinants. Pneumonia can be caused by a wide range of pathogens including bacteria, viruses and fungi, and the etiology varies by epidemiological setting, comorbidities and whether the pneumonia is community-acquired or hospital-acquired. Streptococcus pneumoniae is the major cause of community-acquired bacterial pneumonia while Gram negative bacteria, often resistant to multiple antibiotics, are common causes of hospital-acquired pneumonia and pneumonia in immunosuppressed individuals. Diagnosis is generally clinical and management is based mainly on knowledge of likely causative pathogens as well as clinical severity and presence of known risk factors. Timely and effective antibiotic treatment and oxygen therapy if hypoxemic are critical to patient outcomes. Preventive measures range from improved nutrition and hygiene to specific vaccines that target common causes in children and adults such as the pneumococcal or influenza vaccines

Transthoracic lung aspiration for the aetiological diagnosis of pneumonia: 25 years of experience from The Gambia.

Pneumonia remains the leading cause of death in young children worldwide. Global pneumonia control depends on a good understanding of the aetiology of pneumonia. Percutaneous transthoracic aspiration culture is much more sensitive than blood culture in identifying the aetiological agents of pneumonia. However, the procedure is not widely practised because of lack of familiarity with it and concerns about potential adverse events. We review the diagnostic usefulness and safety of this procedure over 25 years of its use in research and routine practice at the UK Medical Research Council (MRC), The Gambia, and give a detailed description of the procedure itself. Published materials were identified from the MRC's publication database and systematic searches using the PubMed/Medline and Google search engines. Data from a current pneumonia aetiology study in the unit are included together with clinical experience of staff practising at the unit over the period covered in this review. A minimum of 500 lung aspirates were performed over the period of review. Lung aspiration produces a greater yield of diagnostic bacterial isolates than blood culture. It is especially valuable clinically when pathogens not covered by standard empirical antibiotic treatment, such as Mycobacterium tuberculosis and Staphylococcus aureus, are identified. There have been no deaths following the procedure in our setting and a low rate of other complications, all transient. Lung aspiration is currently the most sensitive method for diagnosing pneumonia in children. With appropriate training and precautions it can be safely used for routine diagnosis in suitable referral hospitals

Introduction to the site-specific etiologic results from the pneumonia etiology research for child health (PERCH) study

The Pneumonia Etiology Research for Child Health (PERCH) study evaluated the etiology of severe and very severe pneumonia in children hospitalized in 7 African and Asian countries. Here, we summarize the highlights of in-depth site-specific etiology analyses published separately in this issue, including how etiology varies by age, mortality status, malnutrition, severity, HIV status, and more. These site-specific results impart important lessons that can inform disease control policy implications

Of Lodestars and Lawyers: Incorporating the Duty of Loyalty into the Model Code of Conduct

The “conflicts quartet” of cases decided by the Supreme Court of Canada can be understood as part of a long-standing tension in Anglo-Canadian jurisprudence between two competing conceptions of a lawyer’s professional identity. In the most recent of these cases, C.N. Railway v. McKercher, the Supreme Court conclusively preferred the loyalty-centred conception of the practice of law over the entrepreneurial conception. While the Federation of Law Societies of Canada amended its Model Code of Professional Conduct in 2014 in response to the Supreme Court’s decision in McKercher, this article argues that those amendments did not go far enough. The authors propose a more substantial set of modifications to the Model Code to better entrench the duty of loyalty as a foundational principle of legal ethics. These amendments, they argue, would better reflect the reasoning in McKercher and would provide lawyers with a lodestar to guide their ethical judgement

Discovery and validation of biomarkers to guide clinical management of pneumonia in African children

Background. Pneumonia is the leading cause of death in children globally. Clinical algorithms remain suboptimal for distinguishing between severe pneumonia from other causes of respiratory distress like malaria, and between 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 on 293 Kenyan children with respiratory distress (238 with pneumonia, 41 with P. falciparum malaria and 14 with both). Predictive value was estimated by the area under the receiver operating characteristic curve (AUROC).Results. Lipocalin-2 (Lpc-2) was the best protein biomarker of severe pneumonia (AUROC: 0.71 [95% CI, 0.64-0.79]) and highly predictive of bacteremia (AUROC 78% [95% CI, 64-92%]); pneumococcal bacteremia (AUROC 84% [95% CI, 71-98%]); and ‘probable bacterial etiology’ (AUROC: 91% [95%CI 84-98]). These results were validated in Kenyan children with severe malaria and respiratory distress who also met the WHO 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 (AUROC: 99% [95%CI 99-100%]) and in Kenyan children (AUROC: 82% [95% CI, 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

Should controls with respiratory symptoms be excluded from case-control studies of pneumonia etiology? Reflections from the PERCH study.

Many pneumonia etiology case-control studies exclude controls with respiratory illness from enrollment or analyses. Herein we argue that selecting controls regardless of respiratory symptoms provides the least biased estimates of pneumonia etiology. We review 3 reasons investigators may choose to exclude controls with respiratory symptoms in light of epidemiologic principles of control selection and present data from the Pneumonia Etiology Research for Child Health (PERCH) study where relevant to assess their validity. We conclude that exclusion of controls with respiratory symptoms will result in biased estimates of etiology. Randomly selected community controls, with or without respiratory symptoms, as long as they do not meet the criteria for case-defining pneumonia, are most representative of the general population from which cases arose and the least subject to selection bias