DOCSLIB.ORG

“Radiologically-Confirmed Pneumonia” May Under-Estimate the True Public

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
“Radiologically-Confirmed Pneumonia” May Under-Estimate the True Public Vaccine 25 (2007) 2413–2419 World Health Organisation definition of “radiologically-confirmed pneumonia” may under-estimate the true public health value of conjugate pneumococcal vaccines Shabir A. Madhi ∗, Keith P. Klugman University of the Witwatersrand/Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, South Africa Available online 18 September 2006 Abstract The public health benefit of conjugate pneumococcal vaccine (PCV) in preventing pneumonia would only be appreciated if the tool used for measuring “pneumococcal pneumonia” had good sensitivity. Exploratory studies in South Africa indicate that the sensitivity of “radiologically-confirmed pneumonia” (CXR-AC) underestimates the burden of pneumococcal pneumonia prevented by PCV by as much as 63%. The use of alternate markers such as C-reactive protein enhance the ability of measuring the burden of pneumonia preventable by PCV. A broadened definition of “pneumococcal pneumonia” which includes episodes of pneumonia associated with CXR-AC and those associated with an abnormal chest radiograph other than CXR-AC associated with a CRP of ≥40 mg/l should be considered an a priori outcome in future PCV efficacy trials. © 2006 Elsevier Ltd. All rights reserved. Keywords: Pneumonia; Pneumococcal conjugate vaccine; Prevention; Pneumococcus; Chest radiographs; C-reactive protein 1. Burden of pneumonia and challenges in not vaccinated with H. influenzae type b conjugate vaccine, diagnosing bacterial etiology and Moraxella catarrhalis [6]. These very same bacteria are commonly implicated in the bacterial etiology of community- Over 90% of the estimated 1.8 million annual deaths due acquired pneumonia in children. Due to the high level of to acute respiratory infections in children less than 5 years colonization it is however difficult to distinguish asymp- of age occur in developing countries and are mainly due to tomatic carriage pathogens from true etiological pathogens. bacterial infections [1]. It is estimated that globally 11–20 million of the 146 million annual childhood episodes of pneumonia, 90% of which also occur in developing countries, require hospitalization [2]. A major obstacle to determining 2. Challenges in evaluating the benefits of conjugate pathogen-specific causes of pneumonia is the lack of a sen- pneumococcal pneumonia against pneumonia sitive test for diagnosing bacterial pneumonia [3]. Common bacteria colonizing the nasopharynx in children include Recent advances in vaccinology have resulted in the devel- Streptococcus pneumoniae (25–50%) [4], Staphylococcus opment and introduction of conjugate bacterial vaccines that aureus (20%) [5], Haemophilus influenzae mainly unen- are able to prevent invasive disease as well as mucosal infec- capsulated, but also 6–12% H. influenzae type b in children tions [7–9]. A major impediment to evaluating the efficacy and burden of pneumonia preventable by conjugate bacterial ∗ vaccines is the absence of a validated sensitive and specific Correspondence to: PO Bertsham; Chris Hani-Baragwanath Hospi- method for confirming the pathogen-specific bacterial etiol- tal, Respiratory and Meningeal Pathogens Research Unit; New Nurses Residence-1st Floor West Wing; Bertsham, 2013, South Africa. ogy of pneumonia [10]. Alternate indicators of the disease Tel.: +27 11 989 9885; fax: +27 11 989 9886. targeted by the vaccine are therefore required for measuring E-mail address: [email protected] (S.A. Madhi). the effect of the vaccines against pneumonia. The sensitivity 0264-410X/$ – see front matter © 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2006.09.010 2414 S.A. Madhi, K.P. Klugman / Vaccine 25 (2007) 2413–2419 and specificity of any morphological feature on chest radio- 3. Importance of measuring vaccine preventable graphs in diagnosing non-bacteremic bacterial pneumonia disease and not only vaccine efficacy is uncertain. Some studies suggest that chest radiograph features are unhelpful in discriminating between bacterial Whereas the specificity of the outcome would influence and viral infections in children [11–13]. These studies may the vaccine efficacy calculation in a clinical trial, an outcome however be flawed as the tool for diagnosing “bacterial” with a high specificity but low sensitivity may yield a high pneumonia was not validated for sensitivity or specificity “vaccine efficacy” but underestimate the burden of disease regarding non-bacteremic pneumonia. Many children with that is prevented by the vaccine. As an example (Fig. 1), con- pneumonia in whom a virus but no bacteria were identified sider the scenario where pneumococci were identified in 80% may have had unrecognized bacterial co-infections [14]. of episodes of children with CXR-AC, whereas pneumococci A study in The Gambia demonstrated the efficacy of were identified in only 20% of pneumonia episodes in which H. influenzae type b conjugate vaccine in preventing non- the chest radiograph was categorized as not having CXR-AC. bacteremic radiographically confirmed pneumonia as well In this example CXR-AC would have a higher specificity for as invasive disease [15]. This led to a working-group of the diagnosing “pneumococcal pneumonia” than pneumonia not World Health Organisation proposing to using a chest radio- associated with CXR-AC. graphic outcome as a benchmark for evaluating the efficacy The accurate measurement of the burden of preventable of PCV against pneumococcal pneumonia [16]. The defi- pneumococcal pneumonia would however also depend on nition of radiographically confirmed alveolar consolidation the sensitivity of the outcome used. This is pertinent as only (CXR-AC) agreed upon was: “presence of a dense opacity 16.5–19% of lower respiratory tract episodes among placebo that may be a fluffy consolidation of a portion or whole of a recipients participating in the PCV efficacy trials in The Gam- lobe or of the entire lung, often containing air bronchograms bia and among HIV uninfected children in South Africa had and sometimes associated with pleural effusion, or a pleural evidence of CXR-AC [18,19]. A more recent hospital-based effusion in the lateral pleural space associated with a pul- study on community-acquired pneumonia, the first to use the monary infiltrate, or an effusion large enough to obscure such WHO recommendations for interpreting chest radiographs, an opacity”. showed that 34% of children hospitalized for severe lower The uncertain sensitivity and specificity of CXR-AC respiratory tract infections had CXR-AC [20]. for diagnosing vaccine-serotype specific pneumococcal Continuing with the example, consider that for every 20 pneumonia is further confounded by the potential of pneu- episodes of radiologically-confirmed pneumonia there were mococcal pneumonia to be caused by non-vaccine serotypes. 80 episodes of pneumonia in which the chest radiographs The complexity of determining the effect of a vaccine in the did not show evidence of CXR-AC. The absolute burden of absence of a gold-standard outcome-measure for diagnos- pneumococcal pneumonia prevented would equal the sum of ing bacterial pathogen-specific pneumonia has been reviewed the product of [(number of episodes of specific radiograph [17]. pattern of pneumonia) × (specificity of outcome) × (efficacy Fig. 1. Illustration of effect of specificity and sensitivity of chest radiographs in detecting the burden of pneumococcal pneumonia prevented by conjugate pneumococcal vaccination (PCV). Legend: CXR-AC = World Health Organisation defined radiologically-confirmed pneumonia. Non-CXR-AC = any CXR feature other than presence of CXR-AC. SP = Streptococcus pneumoniae. Non-SP = non-pneumococcal pneumonia episodes. S.A. Madhi, K.P. Klugman / Vaccine 25 (2007) 2413–2419 2415 of vaccine against specific radiographic pattern of pneu- 5. Natural histopathological and radiologic monia)]. Therefore, as illustrated in Fig. 1 assuming that progression in individuals with pneumococcal PCV prevents 50% of pneumococcal pneumonia irrespec- pneumonia tive of the chest radiograph features, the burden of CXR-AC prevented would be (20 episodes × 80% [specificity] × 50% Although most reviews indicate that a homogenous infil- [percentage reduction]) 8 episodes compared with the same trate of a segment or more of a lobe is suggestive of number of pneumococcal pneumonia episodes prevented (i.e. pneumococcus and possibly other bacteria, in all likelihood 80 episodes × 20% [specificity] × 50% [percentage reduc- there is a continuum in the spectrum of the radiographic fea- tion] in which the chest radiograph did not have evidence tures of pneumococcal pneumonia [11,22]. In one study, an of CXR-AC. Hence, the use of CXR-AC alone in such a set- equal number of adult subjects in whom pneumococcal pneu- ting would have under-estimated the burden of pneumonia monia were diagnosed presented with lobar consolidation or prevented by PCV by 50%. bronchopneumonia chest radiographic infiltrates [23]. Measuring the burden of vaccine preventable disease has That there is a spectrum in the radiographic presentation of become all the more important during the course of the eval- pneumococcal pneumonia is expected when considering the uation of conjugate bacterial vaccines since one of the key histopathological changes observed following establishment limitations to the introduction of these vaccines into devel- of pneumococcal infection in the lung. In a susceptible host oped and more so into developing countries would be the in whom there is an imbalance between the host immunity relatively high costs of these vaccines. Therefore, an accu-
Load more

Recommended publications
  • IDSA/ATS Consensus Guidelines on The
    SUPPLEMENT ARTICLE Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults Lionel A. Mandell,1,a Richard G. Wunderink,2,a Antonio Anzueto,3,4 John G. Bartlett,7 G. Douglas Campbell,8 Nathan C. Dean,9,10 Scott F. Dowell,11 Thomas M. File, Jr.12,13 Daniel M. Musher,5,6 Michael S. Niederman,14,15 Antonio Torres,16 and Cynthia G. Whitney11 1McMaster University Medical School, Hamilton, Ontario, Canada; 2Northwestern University Feinberg School of Medicine, Chicago, Illinois; 3University of Texas Health Science Center and 4South Texas Veterans Health Care System, San Antonio, and 5Michael E. DeBakey Veterans Affairs Medical Center and 6Baylor College of Medicine, Houston, Texas; 7Johns Hopkins University School of Medicine, Baltimore, Maryland; 8Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; 9Division of Pulmonary and Critical Care Medicine, LDS Hospital, and 10University of Utah, Salt Lake City, Utah; 11Centers for Disease Control and Prevention, Atlanta, Georgia; 12Northeastern Ohio Universities College of Medicine, Rootstown, and 13Summa Health System, Akron, Ohio; 14State University of New York at Stony Brook, Stony Brook, and 15Department of Medicine, Winthrop University Hospital, Mineola, New York; and 16Cap de Servei de Pneumologia i Alle`rgia Respirato`ria, Institut Clı´nic del To`rax, Hospital Clı´nic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biome`diques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain. EXECUTIVE SUMMARY priate starting point for consultation by specialists. Substantial overlap exists among the patients whom Improving the care of adult patients with community- these guidelines address and those discussed in the re- acquired pneumonia (CAP) has been the focus of many cently published guidelines for health care–associated different organizations, and several have developed pneumonia (HCAP).
    [Show full text]
  • Lung Abscess Due to Streptococcus Pneumoniae: a Case Series and Brief Review of the Literature Ropień Płuca Wywołany Przez S
    PRACAPRACA KAZUISTYCZNA ORYGINALNA Antonello Nicolini1, Catia Cilloniz2, Renata Senarega3, Gianluca Ferraioli4, Cornelius Barlascini5 1Respiratory Diseases Unit, General Hospital, Sestri Levante, Italy 2Department of Pneumology, Institut Clinic del Tórax, Hospital Clinic of Barcelona – Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB) – SGR 911 – Ciber de Enfermedades Respiratorias (Ciberes) Barcelona, Spain 3Radiology Department, General Hospital, Sestri Levante, Italy 4Emergency Department ASL4 Chiavarese, Italy 5Forensic Medicine ASL4 Chiavarese, Italy Lung abscess due to Streptococcus pneumoniae: a case series and brief review of the literature Ropień płuca wywołany przez S. pneumoniae: opis przypadków i przegląd literatury The authors declare no conflict of interest Abstract Anaerobes used to be the most common cause of community-acquired lung abscess, and Streptococcus species used to be the second most common cause. In recent years, this has been changing. Klebsiella pneumoniae is now an increasing cause of commu- nity-acquired lung abscess, but Streptococcus species continue to be major pathogens. Necrotizing pneumonia has generally been regarded as a rare complication of pneumococcal infection in adults. Type 3 Streptococcus pneumoniae was the single most com- mon type implicated in necrosis; however, many other serotypes were implicated. This entity predominately infects children, but is present also in adults. Lung abscess in adults due to Streptococcus pneumoniae is not common. In this regard we present a case series of pulmonary cavitation due to Streptococcus pneumoniae and discuss the possible pathogenic mechanism of the disease. Key words: lung abscess, Streptococcus pneumoniae, pathogenic mechanism Pneumonol. Alergol. Pol. 2014; 82: 276–285 Streszczenie Bakterie beztlenowe stanowiły w przeszłości najczęstszy czynnik etiologiczny pozaszpitalnego ropnia płuca, Streptococcus był na kolejnej pozycji pod względem częstości.
    [Show full text]
  • Is It Influenza Or Pneumonia . . .Or Both?
    Is it Influenza or Pneumonia . .or Both? Norman Moore, Ph.D. Director of Scientific Affairs [email protected] Objectives Discuss the health impacts of pneumonia and influenza in the United States Discuss the diagnostic options available for influenza and pneumonia Discuss the biology of how an influenza infection can predispose a person to pneumococcal pneumonia Infectious Disease in the US 1970: William Stewart, the Surgeon General of the United States declared the U.S. was “ready to close the book on infectious disease as a major health threat”; modern antibiotics, vaccination, and sanitation methods had done the job. 1995: Infectious disease had again become the third leading cause of death, and its incidence is still growing! Current Number of Pneumonia Cases (US) 37 million ambulatory care visits per year for acute respiratory infections (physician and ER visits combined) • Each year 2 - 3 million cases of CAP result in ~ 10 million Community-Acquired physician visits & 500,000 hospitalizations in the US Pneumonia (CAP) • Average mortality is 10-25% in hospitalized patients with CAP • Standard definition: onset of symptoms occurs approx 3 days after admission Hospital-Acquired • 250,000 - 350,000 cases of nosocomial pneumonia per year Pneumonia • 25 - 50% mortality rate Treating Respiratory Diseases in the Emergency Department Influenza and Is the pathogen pneumonia bacterial or symptoms can viral? overlap dramatically If it is flu season, Who do you do you test for test? other pathogens? Different age What do you groups are linked test them for? to different pathogens. Can treatment Stop indiscriminate be impacted if use broad the appropriate spectrum testing is done? antibiotics.
    [Show full text]
  • Animal Models of Pneumococcal Pneumonia
    International Journal of Molecular Sciences Review Animal Models of Pneumococcal pneumonia Noemi Borsa 1,2, Marta Di Pasquale 1 and Marcos I. Restrepo 2,3,* 1 Department of Pathophysiology and Transplantation, University of Milan, Internal Medicine Department, Respiratory unit and Adult Cystic Fibrosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy 2 Division of Pulmonary Diseases and Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA 3 South Texas Veterans Health Care System; San Antonio, TX 78229, USA * Correspondence: [email protected] Received: 14 August 2019; Accepted: 26 August 2019; Published: 28 August 2019 Abstract: Streptococcus pneumoniae remains the most common bacterial pathogen causing lower respiratory tract infections and is a leading cause of morbidity and mortality worldwide, especially in children and the elderly. Another important aspect related to pneumococcal infections is the persistent rate of penicillin and macrolide resistance. Therefore, animal models have been developed to better understand the pathogenesis of pneumococcal disease and test new therapeutic agents and vaccines. This narrative review will focus on the characteristics of the different animal pneumococcal pneumonia models. The assessment of the different animal models will include considerations regarding pneumococcal strains, microbiology properties, procedures used for bacterial inoculation, pathogenesis, clinical characteristics, diagnosis,
    [Show full text]