key: cord-293540-45awgabp
authors: Drancourt, Michel; Gaydos, Charlotte A; Summersgill, James T; Raoult, Didier
title: Point-of-care testing for community-acquired pneumonia
date: 2013-07-23
journal: Lancet Infect Dis
DOI: 10.1016/s1473-3099(13)70165-8
sha: 
doc_id: 293540
cord_uid: 45awgabp

nan

disease, a fi nding that, although not previously noted in infl uenza, has been reported for some viral diseases. 15 During the infl uenza pandemic of 1957, which was caused by the H2N2 subtype, individuals who had previously been infected with the H1N1 virus were less likely to be infected with H2N2 infl uenza than were those who had not. 16 The low incidence of severe H5N1 infections in elderly compared with younger people might be related to the presence of cross-protective antibodies to neuraminidase that are induced by seasonal infl uenza A H1N1 viruses. 17 Overall, we postulate that antibodies to pre-1957 infl uenza A H1N1 viruses protected elderly people against pandemic A H1N1 virus infection, but consequently aff ected the development of heterosubtypic immunity and the disease outcome of H7N9 virus infections. The rate and timing of pandemic A H1N1 virus infections might have revealed the diff erences in H7N9 disease outcome, by contrast with historical infections with seasonal infl uenza A H3N2 viruses. This counterproductive imprinting of immunity might increase susceptibility to H7N9 virus infection. For that reason, older individuals should be given priority for vaccination if sustained person-to-person transmission of H7N9 viruses emerges. To obtain a better understanding of the role of imprinting of the adaptive immune system in H7N9 disease severity, prospective cohort studies in which cross-reactive T-cell immunity and virus-specifi c serum antibodies are tested for are imperative before possible wider spread of the virus. Community-acquired pneumonia is a life-threatening disease. An estimated 8% of patients are admitted to intensive care and overall estimated 30 day mortality is 4-11%. 1 Many bacteria and viruses cause community-acquired pneumonia (and can co-infect), and the causative pathogen (or pathogens) cannot be predicatively identifi ed by any clinical, radiological, or biological methods. 2 Accordingly, antibiotic treatment is empirical, and guidelines recommend a combination of a β lactam with a macrolide. 2,3 Identifi cation of the causative pathogen is usually delayed because clinical specimens are processed in a core laboratory, which is often in a diff erent centre from the patient and the doctor. Culturing, if done, can also take several days.

To avoid this delay, we introduced point-of-care (POC) microbiology laboratories near emergency departments where patients with community-acquired pneumonia are seen fi rst. 4 POC laboratories have a rapid turnaround time (<1·5 h) and deliver results as text messages directly to doctors' mobile phones. 4 POC testing could be implemented in medical centres in large cities, where specimen transport delays diagnosis, and in remote areas without full microbiological facilities. However, it should be noted that not all pathogens that can cause community-acquired pneumonia can be detected by POC tests, and molecular tests for Staphylococus aureus have not been approved by the US Food and Drug Administration (FDA) or the European Conformity (CE).

In the emergency department, communityacquired-pneumonia POC kits, comprising a plastic bag containing prelabelled tubes for clinical samples, prelabelled laboratory forms, and an informed consent form, can be used to take nasal or pharyngeal swabs and urine and serum samples. These samples can be used for the entire panel of POC tests. POC diagnosis of community-acquired pneumonia relies on immunochromatographic assays for the rapid antigen detection of pathogen-specifi c antigen and realtime PCR tests detecting pathogen-specifi c genomic sequences. Three RT-PCR-based POC tests have been approved by the FDA-GeneXpert Flu A/B (Cepheid, Sunnyvale, CA, USA), Simplexa Flu A/B&RSV (Focus Diagnostics, Cypress, CA, USA), and FilmArray RVP (Biofi re, Salt Lake City, UT, USA). The appendix lists FDAapproved and CE-approved tests.

Procalcitonin, a useful biomarker in bacterial community-acquired pneumonia, 5 can be rapidly semiquantifi ed (in 30 min) in serum via immunochromato graphic testing. Urinary rapid anti gen detection of Legionella pneumophila serotype 1 and Streptococcus pneumoniae can be done in 20 min. A metaanalysis 6 showed that urinary detection of L pneumophila had a pooled sensitivity of 0·74 and a specifi city of 0·99. Urinary detection of S pneumoniae had a specifi city of 0·96 and positive predictive value of 0·88-0·96, allowing clinicians to use a narrower spectrum of antibiotics. 7 Rapid antigen detection of the infl uenza virus in nasal or pharyngeal swabs (done in 30 min) has a low sensitivity of less than 0·60; sensitivity correlates with viral load. 8 However, specifi city is around 1·00, resulting in a positive predictive value of more than 0·98-high enough to make a positive result reliable for medical decisions. A negative result does not rule out the presumptive diagnosis of the physician, which should be checked by a second-line molecular test in a core laboratory.

POC tests have to be operator-independent, and thus we do not recommend implementation of microscope-based tests, such as direct fl uorescent antibody tests, for which skilled microscopists are needed. However, a liquid direct fl uorescent antibody format (Fast-Point; Diagnostic Hybrids, Athens, OH, USA) is available for POC testing (appendix). It has not been approved by the FDA or the CE, but detects infl uenza virus, respiratory syncytial virus, adenovirus, coronavirus, and parainfl uenza virus in 25 min. The latest generation real-time PCR kits can complete molecular testing of swabs for bacterial and viral pathogens in 60 min. 9 New generation real-time PCR kits are typically multiplexed assays testing as many as 22 potential pathogens in parallel. 9 This new capacity of POC tests increases the number of diagnoses 11 and underscores that community-acquired pneumonia can result from co-infection with several pathogens, 10 which will challenge common notions about causation and management. For example, we propose that infl uenza and S pneumoniae have to be tested for in parallel irrespective of which one is the presumed causative pathogen. Furthermore, detection by POC testing of an abnormal increase in group A streptococci might suggest co-infection with infl uenza. 11 Procalcitonin concentrations greater than 0·5 ng/mL suggest bacterial co-infection in infl uenza-a major risk factor for death.

POC results could aff ect the major decisions that doctors have to make in emergency departmentseg, whether to admit the patient (the usual action for community-acquired pneumonia), which antibiotic (such as balancing the advantages of β-lactam and macrolides 12 ) or antiviral to prescribe, isolation of contagious patients. Although barriers to the implementation of POC tests in developing countries have been identifi ed, POC tests have been successfully implemented in remote areas-eg, rural Senegal, where patients and health-care providers are in close contact. 13 Furthermore, assessment of the numbers of POC tests done on a weekly basis could help to predict epidemics even before the causative organism is known.

See Online for appendix

In May, 2012, on the Attorney General's order, the police publicised photos and identity details of 18 women working illegally as sex workers in Athens, Greece, who had been arrested and found to be HIV positive. The rationale for this decision was presumably protection of the public-people who had had sexual intercourse with these sex workers might recognise them and seek medical advice and HIV testing, whereas people who pay for sex could avoid contact with these particular workers. Five of the sex workers were prosecuted for intentional grievous harm-ie, transmission of HIV. The case drew media attention and sparked controversy for a brief period, but was forgotten amid pressing problems related to the economic crisis. On March 11, 2013, the fi ve women were acquitted, but this news did not make headlines. Some important ethical issues were raised, which need to be adequately addressed both in Greece and internationally.

Sex work in Greece is legal and regulated; sex workers must register at their local prefecture and carry a medical card that is updated every 2 weeks. However, fewer than 1000 women are estimated to be legally employed as sex workers, whereas roughly 20 000 women, mostly of foreign origin, are thought to be engaged in illegal sex work. 1 Greece is not unique in this regard-by and large, the sex industry evades control worldwide. Notwithstanding the diversity of sex work settings and its many problematic aspects, such as human traffi cking, sex workers' health has gained the attention of policy makers, which is shown by a growing body of published guidelines and strategies. 2 Is the aim of these strategies to protect sex workers or to protect public health via protection of sex workers? If the outcome is the same either way, does the intent make a diff erence?

The Greek authorities' handling of the 18 HIVpositive sex workers shows an obvious diff erence between the two aims. Researchers from other countries have already pointed out that public health offi cials are concerned less about the health of sex workers than about that of the sex workers' clients or the larger community. 3 The public health response to sex workers is often one sided. 4 In breach of key This online publication has been corrected. The corrected version fi rst appeared at thelancet. com/infection on Feb 24, 2014

Systematic review and metaanalysis: urinary antigen tests for Legionellosis

Current and potential usefulness of pneumococcal urinary antigen detection in hospitalized patients with community-acquired pneumonia to guide antimicrobial therapy

Evaluation of fi ve rapid diagnostic kits for infl uenza A/B virus

Respiratory virus detection in immunocompromised patients with FilmArray respiratory panel compared to conventional methods

Associations between pathogens in the upper respiratory tract of young children: interplay between viruses and bacteria

Group A streptococcal infections during the seasonal infl uenza outbreak 2010/11 in south east England

A clinical solution to antimicrobial resistance in communityacquired pneumonia: narrowing the spectrum of antimicrobial therapy: comment on "Current and potential usefulness of pneumococcal urinary antigen detection in hospitalized patients with community-acquired pneumonia to guide antimicrobial therapy

Point-of-care laboratory pathogens diagnosis in rural Senegal