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Adjuvant corticosteroids in hospitalized patients with CAP
When is it appropriate to treat?
Case
A 55-year-old male with a history of tobacco use disorder presents with 2 days of productive cough, fever, chills, and mild shortness of breath. T 38.4, HR 89, RR 32, BP 100/65, 02 sat 86% on room air. Exam reveals diminished breath sounds and positive egophony over the right lung base. WBC is 16,000 and BUN 22. Chest x-ray reveals right lower lobe consolidation. He is given ceftriaxone and azithromycin.
Brief overview of the issue
Community-acquired pneumonia (CAP) is the leading cause of infectious disease–related death in the United States. Mortality associated with CAP is estimated at 57,000 deaths annually and occurs largely in patients requiring hospitalization.1 The 30-day mortality rate in patients who are hospitalized for CAP is approximately 10%-12%.2 After discharge from the hospital, about 18% of patients are readmitted within 30 days.3 An excessive inflammatory cytokine response may be a major contributor to the high mortality rate in CAP and systemic corticosteroids may reduce the inflammatory response from the infection by down-regulating this proinflammatory cytokine production.
Almost all of the major decisions regarding management of CAP, including diagnostic and treatment issues, revolve around the initial assessment of severity of illness. Between 40% and 60% of patients who present to the emergency department with CAP are admitted4 and approximately 10% of hospitalized patients with CAP require ICU admission.5 Validated instruments such as CURB-65, the pneumonia severity index (PSI), and guidelines from the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) may predict severity of illness but should always be supplemented with physician determination of subjective factors when determining treatment.5 Although there is no census definition of severe pneumonia, studies generally define the condition in the following order of preference: PSI score of IV or V followed by CURB-65 score of two or greater. If these scoring modalities were not available, the IDSA/ATS criteria was used (1 major or 3 minor). Others define severe CAP as pneumonia requiring supportive therapy within a critical care environment.
Overview of the data
The use of corticosteroids in addition to antibiotics in the treatment of CAP was proposed as early as the 1950s and yet only in the last decade has the body of evidence grown significantly.5 There is evidence that corticosteroids suppress inflammation without acutely impairing the immune response as evidenced by a rapid and sustained decrease in circulating inflammatory markers such as C-reactive protein and interleukin 6 and no effect on the anti-inflammatory interleukin 10.6 Within the last year, three meta-analyses, one by the Cochrane Library, one by the IDSA, and a third in the American Journal of Emergency Medicine, addressed the role of routine low dose (20-60 mg of prednisone or equivalent), short-course (3-7 days) systemic corticosteroids in hospitalized patients with CAP of varying severities.
The Cochrane meta-analysis, the largest and most recent dataset, included 13 trials with a combined 1,954 adult patients and found that corticosteroids significantly lowered mortality in hospitalized patients with severe CAP with a number needed to treat of 19.7 In this group with severe CAP, mortality was lowered from 13% to 8% and there were significantly fewer episodes of respiratory failure and shock with the addition of corticosteroids. No effect was seen on mortality in patients with less severe CAP. In those patients who received adjuvant corticosteroids, length of hospital stay decreased by 3 days, regardless of CAP severity.7
The IDSA meta-analysis was similar and included 1,506 patients from six trials.8 In contrast with the Cochrane study, this analysis found corticosteroids did not significantly lower mortality in patients with severe CAP but did reduce time to clinical stability and length of hospital stay by over 1 day. This study also found significantly more CAP-related, 30-day rehospitalizations (5% vs. 3%; defined as recurrent pneumonia, other infection, pleuritic pain, adverse cardiovascular event, or diarrhea) in patient with non-severe CAP treated with corticosteroids.
The study in the American Journal of Emergency Medicine involved ten trials involving more than 700 patients admitted with severe CAP and found in-hospital mortality was cut in half (RR 0.49) and length of hospital stay was reduced when patients were treated with corticosteroids in addition to standard antibiotic therapy.9
In 2015, two randomized clinical trials, one in the Lancet and the other in JAMA, and a meta-analysis in Annals of Internal Medicine assessed the impact of adjuvant corticosteroids in the treatment of hospitalized patients with CAP. The Lancet study of 785 patients hospitalized with CAP of any severity found shortened time to clinical stability (3.0 vs. 4.4 days) as defined by stable vital signs, improved oral intake, and normalized mental status for greater than 24 hours when oral prednisone 50 mg for 7 days was added to standard therapy.10 Patients in the treatment group were also discharged 1 day earlier compared with the placebo control group.
The study in JAMA was small, with only 100 patients at three teaching hospitals in Spain, but found that patients hospitalized with severe CAP and high inflammatory response based on elevated C-reactive protein were less likely to experience a treatment failure, defined as shock, mechanical ventilation, death, or radiographic progression, when intravenous methylprednisolone 0.5 mg/kg was added to standard antibiotic therapy.11
Finally, the meta-analysis in Annals of Internal Medicine assessed 13 randomized controlled placebo trials of 1,974 patients and found that adjuvant corticosteroids in a dose of 20-60 mg of prednisone or equivalent total daily dose significantly lowered mortality in patients with severe CAP and incidence of respiratory distress syndrome, and need for mechanical ventilation in all patients hospitalized with CAP.12
Importantly, nearly all of the described studies showed a significantly higher incidence of hyperglycemia in patients who received corticosteroids.
Application of the data to our patients
The benefit of adjuvant corticosteroids is most clear in hospitalized patients with severe CAP. Recent, strong evidence supports decreased mortality, decreased time to clinical stability, and decreased length of stay in our patient, with severe CAP, if treated with 20-60 mg of prednisone or equivalent total daily dose for 3-7 days. For patients with non-severe CAP, we suggest taking a risk-benefit approach based on other comorbidities, as the risk for CAP-related rehospitalizations may be higher.
For patients with underlying lung disease, specifically COPD or reactive airway disease, we suggest a low threshold for adding corticosteroids. This approach is more anecdotal than data driven, though corticosteroids are a mainstay of treatment for COPD exacerbations and a retrospective analysis of more than 20,000 hospitalized children with CAP and wheezing revealed decreased length of stay with corticosteroid treatment.13 Furthermore, a number of the studies described above included patients with COPD. Our threshold rises significantly in patients with poorly controlled diabetes mellitus.
Bottom line
For patients hospitalized with severe community-acquired pneumonia, recent evidence supports the use of low dose, short-course, systemic corticosteroids in addition to standard therapy.
Dr. Parsons is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center in Charlottesville, Va. Dr. Miller is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center. Dr. Hoke is Associate Director of Hospital Medicine and Faculty Development at the University of Virginia.
References
1. Ramirez J et al. Adults hospitalized with pneumonia in the United States: Incidence, epidemiology, and mortality. Clin Infect Dis. 2017 Dec 1:65(11):1806-12.
2. Musher D et al. Community-acquired pneumonia: Review article. N Engl J Med. 2014 Oct 23;371:1619-28.
3. Wunderink R et al. Community-aquired pneumonia: Clinical practice. N Engl J Med. 2014 Feb 6;370:543-51.
4. Mandell L et al. Infectious Diseases Society America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007;44:S27-72.
5. Wagner HN et al. The effect of hydrocortisone upon the course of pneumococcal pneumonia treated with penicillin. Bull Johns Hopkins Hosp. 1956;98:197-215.
6. Polverino E et al. Systemic corticosteroids for community-acquired pneumonia: Reasons for use and lack of benefit on outcome. Respirology. 2013. Feb;18(2):263-71 (https://doi.org/10.1111/resp.12013).
7. Stern A et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13; 12:CD007720 (https://doi.org/10.1002/14651858.CD007720.pub3).
8. Briel M et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1;66:346 (https://doi.org/10.1093/cid/cix801).
9. Wu W-F et al. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A meta-analysis. Am J Emerg Med. 2017 Jul 15; [e-pub] (http://dx.doi.org/10.1016/j.ajem.2017.07.050).
10. Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015 Jan 18; [e-pub ahead of print] (http://dx.doi.org/10.1016/S0140-6736[14]62447-8).
11. Torres A et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA 2015 Feb 17; 313:677 (http://dx.doi.org/10.1001/jama.2015.88).
12. Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6;163:519 (http://dx.doi.org/10.7326/M15-0715).
13. Simon LH et al. Management of community-acquired pneumonia in hospitalized children. Current Treat Options Peds (2015) 1:59 (https://doi:.org/10.1007/s40746-014-0011-3).
Key points
• For patients hospitalized with severe CAP, recent evidence supports the use of low-dose, short-course, systemic corticosteroids in addition to standard therapy.
• Among hospitalized patients with non-severe CAP, the benefit is not well defined. Studies suggest these patients may benefit from reduced time to clinical stability and reduced length of hospital stay. However, they may be at risk for significantly more CAP-related, 30-day rehospitalizations and hyperglycemia.
• Further prospective, randomized controlled studies are needed to further delineate the patient population who will most benefit from adjunctive corticosteroids use, including dose and duration of treatment.
QUIZ
Which of the following is FALSE regarding community acquired pneumonia?
A. CAP is the leading cause of infectious disease related death in the United States.
B. An excessive inflammatory cytokine response may contribute to the high mortality rate in CAP.
C. Adjunctive steroid therapy has been shown to decrease mortality in all patients with CAP.
D. Hyperglycemia occurs more frequently in patients receiving steroid therapy.
E. Reasons to avoid adjunctive steroid therapy in CAP include low risk for mortality, poorly controlled diabetes, suspected viral or fungal etiology, and elevated risk for gastrointestinal bleeding.
ANSWER: C. The patient population that may benefit most from the use of adjuvant corticosteroids is poorly defined. However, in patients with severe pneumonia, the use of adjuvant steroids has been shown to decrease mortality, time to clinical stability, and length of stay.
Additional reading
Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6; 163:519. (http://dx.doi.org/10.7326/M15-0715).
Briel M et al. Corticosteroids in patients hospitalized with community-acquired Pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1; 66:346 (https://doi.org/10.1093/cid/cix801).
Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015 Jan 18; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(14)62447-8).
Feldman C et al. Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials. J Thorac Dis. 2016 Mar; 8(3):E162-E171.
Wan YD et al. Efficacy and safety of corticosteroids for community-acquired pneumonia: A systemic review and meta-analysis. Chest. 2016 Jan;149(1):209-19.
When is it appropriate to treat?
When is it appropriate to treat?
Case
A 55-year-old male with a history of tobacco use disorder presents with 2 days of productive cough, fever, chills, and mild shortness of breath. T 38.4, HR 89, RR 32, BP 100/65, 02 sat 86% on room air. Exam reveals diminished breath sounds and positive egophony over the right lung base. WBC is 16,000 and BUN 22. Chest x-ray reveals right lower lobe consolidation. He is given ceftriaxone and azithromycin.
Brief overview of the issue
Community-acquired pneumonia (CAP) is the leading cause of infectious disease–related death in the United States. Mortality associated with CAP is estimated at 57,000 deaths annually and occurs largely in patients requiring hospitalization.1 The 30-day mortality rate in patients who are hospitalized for CAP is approximately 10%-12%.2 After discharge from the hospital, about 18% of patients are readmitted within 30 days.3 An excessive inflammatory cytokine response may be a major contributor to the high mortality rate in CAP and systemic corticosteroids may reduce the inflammatory response from the infection by down-regulating this proinflammatory cytokine production.
Almost all of the major decisions regarding management of CAP, including diagnostic and treatment issues, revolve around the initial assessment of severity of illness. Between 40% and 60% of patients who present to the emergency department with CAP are admitted4 and approximately 10% of hospitalized patients with CAP require ICU admission.5 Validated instruments such as CURB-65, the pneumonia severity index (PSI), and guidelines from the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) may predict severity of illness but should always be supplemented with physician determination of subjective factors when determining treatment.5 Although there is no census definition of severe pneumonia, studies generally define the condition in the following order of preference: PSI score of IV or V followed by CURB-65 score of two or greater. If these scoring modalities were not available, the IDSA/ATS criteria was used (1 major or 3 minor). Others define severe CAP as pneumonia requiring supportive therapy within a critical care environment.
Overview of the data
The use of corticosteroids in addition to antibiotics in the treatment of CAP was proposed as early as the 1950s and yet only in the last decade has the body of evidence grown significantly.5 There is evidence that corticosteroids suppress inflammation without acutely impairing the immune response as evidenced by a rapid and sustained decrease in circulating inflammatory markers such as C-reactive protein and interleukin 6 and no effect on the anti-inflammatory interleukin 10.6 Within the last year, three meta-analyses, one by the Cochrane Library, one by the IDSA, and a third in the American Journal of Emergency Medicine, addressed the role of routine low dose (20-60 mg of prednisone or equivalent), short-course (3-7 days) systemic corticosteroids in hospitalized patients with CAP of varying severities.
The Cochrane meta-analysis, the largest and most recent dataset, included 13 trials with a combined 1,954 adult patients and found that corticosteroids significantly lowered mortality in hospitalized patients with severe CAP with a number needed to treat of 19.7 In this group with severe CAP, mortality was lowered from 13% to 8% and there were significantly fewer episodes of respiratory failure and shock with the addition of corticosteroids. No effect was seen on mortality in patients with less severe CAP. In those patients who received adjuvant corticosteroids, length of hospital stay decreased by 3 days, regardless of CAP severity.7
The IDSA meta-analysis was similar and included 1,506 patients from six trials.8 In contrast with the Cochrane study, this analysis found corticosteroids did not significantly lower mortality in patients with severe CAP but did reduce time to clinical stability and length of hospital stay by over 1 day. This study also found significantly more CAP-related, 30-day rehospitalizations (5% vs. 3%; defined as recurrent pneumonia, other infection, pleuritic pain, adverse cardiovascular event, or diarrhea) in patient with non-severe CAP treated with corticosteroids.
The study in the American Journal of Emergency Medicine involved ten trials involving more than 700 patients admitted with severe CAP and found in-hospital mortality was cut in half (RR 0.49) and length of hospital stay was reduced when patients were treated with corticosteroids in addition to standard antibiotic therapy.9
In 2015, two randomized clinical trials, one in the Lancet and the other in JAMA, and a meta-analysis in Annals of Internal Medicine assessed the impact of adjuvant corticosteroids in the treatment of hospitalized patients with CAP. The Lancet study of 785 patients hospitalized with CAP of any severity found shortened time to clinical stability (3.0 vs. 4.4 days) as defined by stable vital signs, improved oral intake, and normalized mental status for greater than 24 hours when oral prednisone 50 mg for 7 days was added to standard therapy.10 Patients in the treatment group were also discharged 1 day earlier compared with the placebo control group.
The study in JAMA was small, with only 100 patients at three teaching hospitals in Spain, but found that patients hospitalized with severe CAP and high inflammatory response based on elevated C-reactive protein were less likely to experience a treatment failure, defined as shock, mechanical ventilation, death, or radiographic progression, when intravenous methylprednisolone 0.5 mg/kg was added to standard antibiotic therapy.11
Finally, the meta-analysis in Annals of Internal Medicine assessed 13 randomized controlled placebo trials of 1,974 patients and found that adjuvant corticosteroids in a dose of 20-60 mg of prednisone or equivalent total daily dose significantly lowered mortality in patients with severe CAP and incidence of respiratory distress syndrome, and need for mechanical ventilation in all patients hospitalized with CAP.12
Importantly, nearly all of the described studies showed a significantly higher incidence of hyperglycemia in patients who received corticosteroids.
Application of the data to our patients
The benefit of adjuvant corticosteroids is most clear in hospitalized patients with severe CAP. Recent, strong evidence supports decreased mortality, decreased time to clinical stability, and decreased length of stay in our patient, with severe CAP, if treated with 20-60 mg of prednisone or equivalent total daily dose for 3-7 days. For patients with non-severe CAP, we suggest taking a risk-benefit approach based on other comorbidities, as the risk for CAP-related rehospitalizations may be higher.
For patients with underlying lung disease, specifically COPD or reactive airway disease, we suggest a low threshold for adding corticosteroids. This approach is more anecdotal than data driven, though corticosteroids are a mainstay of treatment for COPD exacerbations and a retrospective analysis of more than 20,000 hospitalized children with CAP and wheezing revealed decreased length of stay with corticosteroid treatment.13 Furthermore, a number of the studies described above included patients with COPD. Our threshold rises significantly in patients with poorly controlled diabetes mellitus.
Bottom line
For patients hospitalized with severe community-acquired pneumonia, recent evidence supports the use of low dose, short-course, systemic corticosteroids in addition to standard therapy.
Dr. Parsons is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center in Charlottesville, Va. Dr. Miller is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center. Dr. Hoke is Associate Director of Hospital Medicine and Faculty Development at the University of Virginia.
References
1. Ramirez J et al. Adults hospitalized with pneumonia in the United States: Incidence, epidemiology, and mortality. Clin Infect Dis. 2017 Dec 1:65(11):1806-12.
2. Musher D et al. Community-acquired pneumonia: Review article. N Engl J Med. 2014 Oct 23;371:1619-28.
3. Wunderink R et al. Community-aquired pneumonia: Clinical practice. N Engl J Med. 2014 Feb 6;370:543-51.
4. Mandell L et al. Infectious Diseases Society America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007;44:S27-72.
5. Wagner HN et al. The effect of hydrocortisone upon the course of pneumococcal pneumonia treated with penicillin. Bull Johns Hopkins Hosp. 1956;98:197-215.
6. Polverino E et al. Systemic corticosteroids for community-acquired pneumonia: Reasons for use and lack of benefit on outcome. Respirology. 2013. Feb;18(2):263-71 (https://doi.org/10.1111/resp.12013).
7. Stern A et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13; 12:CD007720 (https://doi.org/10.1002/14651858.CD007720.pub3).
8. Briel M et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1;66:346 (https://doi.org/10.1093/cid/cix801).
9. Wu W-F et al. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A meta-analysis. Am J Emerg Med. 2017 Jul 15; [e-pub] (http://dx.doi.org/10.1016/j.ajem.2017.07.050).
10. Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015 Jan 18; [e-pub ahead of print] (http://dx.doi.org/10.1016/S0140-6736[14]62447-8).
11. Torres A et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA 2015 Feb 17; 313:677 (http://dx.doi.org/10.1001/jama.2015.88).
12. Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6;163:519 (http://dx.doi.org/10.7326/M15-0715).
13. Simon LH et al. Management of community-acquired pneumonia in hospitalized children. Current Treat Options Peds (2015) 1:59 (https://doi:.org/10.1007/s40746-014-0011-3).
Key points
• For patients hospitalized with severe CAP, recent evidence supports the use of low-dose, short-course, systemic corticosteroids in addition to standard therapy.
• Among hospitalized patients with non-severe CAP, the benefit is not well defined. Studies suggest these patients may benefit from reduced time to clinical stability and reduced length of hospital stay. However, they may be at risk for significantly more CAP-related, 30-day rehospitalizations and hyperglycemia.
• Further prospective, randomized controlled studies are needed to further delineate the patient population who will most benefit from adjunctive corticosteroids use, including dose and duration of treatment.
QUIZ
Which of the following is FALSE regarding community acquired pneumonia?
A. CAP is the leading cause of infectious disease related death in the United States.
B. An excessive inflammatory cytokine response may contribute to the high mortality rate in CAP.
C. Adjunctive steroid therapy has been shown to decrease mortality in all patients with CAP.
D. Hyperglycemia occurs more frequently in patients receiving steroid therapy.
E. Reasons to avoid adjunctive steroid therapy in CAP include low risk for mortality, poorly controlled diabetes, suspected viral or fungal etiology, and elevated risk for gastrointestinal bleeding.
ANSWER: C. The patient population that may benefit most from the use of adjuvant corticosteroids is poorly defined. However, in patients with severe pneumonia, the use of adjuvant steroids has been shown to decrease mortality, time to clinical stability, and length of stay.
Additional reading
Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6; 163:519. (http://dx.doi.org/10.7326/M15-0715).
Briel M et al. Corticosteroids in patients hospitalized with community-acquired Pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1; 66:346 (https://doi.org/10.1093/cid/cix801).
Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015 Jan 18; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(14)62447-8).
Feldman C et al. Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials. J Thorac Dis. 2016 Mar; 8(3):E162-E171.
Wan YD et al. Efficacy and safety of corticosteroids for community-acquired pneumonia: A systemic review and meta-analysis. Chest. 2016 Jan;149(1):209-19.
Case
A 55-year-old male with a history of tobacco use disorder presents with 2 days of productive cough, fever, chills, and mild shortness of breath. T 38.4, HR 89, RR 32, BP 100/65, 02 sat 86% on room air. Exam reveals diminished breath sounds and positive egophony over the right lung base. WBC is 16,000 and BUN 22. Chest x-ray reveals right lower lobe consolidation. He is given ceftriaxone and azithromycin.
Brief overview of the issue
Community-acquired pneumonia (CAP) is the leading cause of infectious disease–related death in the United States. Mortality associated with CAP is estimated at 57,000 deaths annually and occurs largely in patients requiring hospitalization.1 The 30-day mortality rate in patients who are hospitalized for CAP is approximately 10%-12%.2 After discharge from the hospital, about 18% of patients are readmitted within 30 days.3 An excessive inflammatory cytokine response may be a major contributor to the high mortality rate in CAP and systemic corticosteroids may reduce the inflammatory response from the infection by down-regulating this proinflammatory cytokine production.
Almost all of the major decisions regarding management of CAP, including diagnostic and treatment issues, revolve around the initial assessment of severity of illness. Between 40% and 60% of patients who present to the emergency department with CAP are admitted4 and approximately 10% of hospitalized patients with CAP require ICU admission.5 Validated instruments such as CURB-65, the pneumonia severity index (PSI), and guidelines from the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) may predict severity of illness but should always be supplemented with physician determination of subjective factors when determining treatment.5 Although there is no census definition of severe pneumonia, studies generally define the condition in the following order of preference: PSI score of IV or V followed by CURB-65 score of two or greater. If these scoring modalities were not available, the IDSA/ATS criteria was used (1 major or 3 minor). Others define severe CAP as pneumonia requiring supportive therapy within a critical care environment.
Overview of the data
The use of corticosteroids in addition to antibiotics in the treatment of CAP was proposed as early as the 1950s and yet only in the last decade has the body of evidence grown significantly.5 There is evidence that corticosteroids suppress inflammation without acutely impairing the immune response as evidenced by a rapid and sustained decrease in circulating inflammatory markers such as C-reactive protein and interleukin 6 and no effect on the anti-inflammatory interleukin 10.6 Within the last year, three meta-analyses, one by the Cochrane Library, one by the IDSA, and a third in the American Journal of Emergency Medicine, addressed the role of routine low dose (20-60 mg of prednisone or equivalent), short-course (3-7 days) systemic corticosteroids in hospitalized patients with CAP of varying severities.
The Cochrane meta-analysis, the largest and most recent dataset, included 13 trials with a combined 1,954 adult patients and found that corticosteroids significantly lowered mortality in hospitalized patients with severe CAP with a number needed to treat of 19.7 In this group with severe CAP, mortality was lowered from 13% to 8% and there were significantly fewer episodes of respiratory failure and shock with the addition of corticosteroids. No effect was seen on mortality in patients with less severe CAP. In those patients who received adjuvant corticosteroids, length of hospital stay decreased by 3 days, regardless of CAP severity.7
The IDSA meta-analysis was similar and included 1,506 patients from six trials.8 In contrast with the Cochrane study, this analysis found corticosteroids did not significantly lower mortality in patients with severe CAP but did reduce time to clinical stability and length of hospital stay by over 1 day. This study also found significantly more CAP-related, 30-day rehospitalizations (5% vs. 3%; defined as recurrent pneumonia, other infection, pleuritic pain, adverse cardiovascular event, or diarrhea) in patient with non-severe CAP treated with corticosteroids.
The study in the American Journal of Emergency Medicine involved ten trials involving more than 700 patients admitted with severe CAP and found in-hospital mortality was cut in half (RR 0.49) and length of hospital stay was reduced when patients were treated with corticosteroids in addition to standard antibiotic therapy.9
In 2015, two randomized clinical trials, one in the Lancet and the other in JAMA, and a meta-analysis in Annals of Internal Medicine assessed the impact of adjuvant corticosteroids in the treatment of hospitalized patients with CAP. The Lancet study of 785 patients hospitalized with CAP of any severity found shortened time to clinical stability (3.0 vs. 4.4 days) as defined by stable vital signs, improved oral intake, and normalized mental status for greater than 24 hours when oral prednisone 50 mg for 7 days was added to standard therapy.10 Patients in the treatment group were also discharged 1 day earlier compared with the placebo control group.
The study in JAMA was small, with only 100 patients at three teaching hospitals in Spain, but found that patients hospitalized with severe CAP and high inflammatory response based on elevated C-reactive protein were less likely to experience a treatment failure, defined as shock, mechanical ventilation, death, or radiographic progression, when intravenous methylprednisolone 0.5 mg/kg was added to standard antibiotic therapy.11
Finally, the meta-analysis in Annals of Internal Medicine assessed 13 randomized controlled placebo trials of 1,974 patients and found that adjuvant corticosteroids in a dose of 20-60 mg of prednisone or equivalent total daily dose significantly lowered mortality in patients with severe CAP and incidence of respiratory distress syndrome, and need for mechanical ventilation in all patients hospitalized with CAP.12
Importantly, nearly all of the described studies showed a significantly higher incidence of hyperglycemia in patients who received corticosteroids.
Application of the data to our patients
The benefit of adjuvant corticosteroids is most clear in hospitalized patients with severe CAP. Recent, strong evidence supports decreased mortality, decreased time to clinical stability, and decreased length of stay in our patient, with severe CAP, if treated with 20-60 mg of prednisone or equivalent total daily dose for 3-7 days. For patients with non-severe CAP, we suggest taking a risk-benefit approach based on other comorbidities, as the risk for CAP-related rehospitalizations may be higher.
For patients with underlying lung disease, specifically COPD or reactive airway disease, we suggest a low threshold for adding corticosteroids. This approach is more anecdotal than data driven, though corticosteroids are a mainstay of treatment for COPD exacerbations and a retrospective analysis of more than 20,000 hospitalized children with CAP and wheezing revealed decreased length of stay with corticosteroid treatment.13 Furthermore, a number of the studies described above included patients with COPD. Our threshold rises significantly in patients with poorly controlled diabetes mellitus.
Bottom line
For patients hospitalized with severe community-acquired pneumonia, recent evidence supports the use of low dose, short-course, systemic corticosteroids in addition to standard therapy.
Dr. Parsons is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center in Charlottesville, Va. Dr. Miller is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center. Dr. Hoke is Associate Director of Hospital Medicine and Faculty Development at the University of Virginia.
References
1. Ramirez J et al. Adults hospitalized with pneumonia in the United States: Incidence, epidemiology, and mortality. Clin Infect Dis. 2017 Dec 1:65(11):1806-12.
2. Musher D et al. Community-acquired pneumonia: Review article. N Engl J Med. 2014 Oct 23;371:1619-28.
3. Wunderink R et al. Community-aquired pneumonia: Clinical practice. N Engl J Med. 2014 Feb 6;370:543-51.
4. Mandell L et al. Infectious Diseases Society America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007;44:S27-72.
5. Wagner HN et al. The effect of hydrocortisone upon the course of pneumococcal pneumonia treated with penicillin. Bull Johns Hopkins Hosp. 1956;98:197-215.
6. Polverino E et al. Systemic corticosteroids for community-acquired pneumonia: Reasons for use and lack of benefit on outcome. Respirology. 2013. Feb;18(2):263-71 (https://doi.org/10.1111/resp.12013).
7. Stern A et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13; 12:CD007720 (https://doi.org/10.1002/14651858.CD007720.pub3).
8. Briel M et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1;66:346 (https://doi.org/10.1093/cid/cix801).
9. Wu W-F et al. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A meta-analysis. Am J Emerg Med. 2017 Jul 15; [e-pub] (http://dx.doi.org/10.1016/j.ajem.2017.07.050).
10. Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015 Jan 18; [e-pub ahead of print] (http://dx.doi.org/10.1016/S0140-6736[14]62447-8).
11. Torres A et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA 2015 Feb 17; 313:677 (http://dx.doi.org/10.1001/jama.2015.88).
12. Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6;163:519 (http://dx.doi.org/10.7326/M15-0715).
13. Simon LH et al. Management of community-acquired pneumonia in hospitalized children. Current Treat Options Peds (2015) 1:59 (https://doi:.org/10.1007/s40746-014-0011-3).
Key points
• For patients hospitalized with severe CAP, recent evidence supports the use of low-dose, short-course, systemic corticosteroids in addition to standard therapy.
• Among hospitalized patients with non-severe CAP, the benefit is not well defined. Studies suggest these patients may benefit from reduced time to clinical stability and reduced length of hospital stay. However, they may be at risk for significantly more CAP-related, 30-day rehospitalizations and hyperglycemia.
• Further prospective, randomized controlled studies are needed to further delineate the patient population who will most benefit from adjunctive corticosteroids use, including dose and duration of treatment.
QUIZ
Which of the following is FALSE regarding community acquired pneumonia?
A. CAP is the leading cause of infectious disease related death in the United States.
B. An excessive inflammatory cytokine response may contribute to the high mortality rate in CAP.
C. Adjunctive steroid therapy has been shown to decrease mortality in all patients with CAP.
D. Hyperglycemia occurs more frequently in patients receiving steroid therapy.
E. Reasons to avoid adjunctive steroid therapy in CAP include low risk for mortality, poorly controlled diabetes, suspected viral or fungal etiology, and elevated risk for gastrointestinal bleeding.
ANSWER: C. The patient population that may benefit most from the use of adjuvant corticosteroids is poorly defined. However, in patients with severe pneumonia, the use of adjuvant steroids has been shown to decrease mortality, time to clinical stability, and length of stay.
Additional reading
Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6; 163:519. (http://dx.doi.org/10.7326/M15-0715).
Briel M et al. Corticosteroids in patients hospitalized with community-acquired Pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1; 66:346 (https://doi.org/10.1093/cid/cix801).
Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015 Jan 18; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(14)62447-8).
Feldman C et al. Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials. J Thorac Dis. 2016 Mar; 8(3):E162-E171.
Wan YD et al. Efficacy and safety of corticosteroids for community-acquired pneumonia: A systemic review and meta-analysis. Chest. 2016 Jan;149(1):209-19.
FDA warns about fecal microbiota for transplantation
Officials at the Food and Drug Administration have issued a safety alert regarding the use of fecal microbiota for transplantation and the risk of serious adverse reactions because of transmission of multidrug-resistant organisms (MDROs).
According to the alert, which was issued on June 13, 2019, the agency became aware of two immunocompromised adult patients who received investigational fecal microbiota for transplantation (FMT) and developed extended-spectrum beta-lactamase (EBSL)–producing Escherichia coli. One of the patients died.
“This is certainly a theoretical risk that we’ve known about,” Lea Ann Chen, MD, a gastroenterologist at New York University, said in an interview. “This announcement is important, because we probably don’t counsel patients specifically about this risk. We say there is a risk for transmission of infectious agents in general, but I think that probably very few counsel patients about a risk for transmission of MDROs.”
The donor stool and FMT used in the two patients were not tested for ESBL-producing gram-negative organisms prior to use.
As a result of these serious adverse reactions, the FDA has determined that the following donor screening and stool testing protections are needed for any investigational use of FMT.
- Donor screening with questions that specifically address risk factors for colonization with MDROs, and exclusion of individuals at higher risk of colonization with MDROs.
- MDRO testing of donor stool and exclusion of stool that tests positive for MDRO. FDA scientists have determined the specific MDRO testing and frequency that should be implemented.
On June 14, the American Gastroenterological Association sent a communication about the FDA alert to its members, which stated that the AGA “is committed to advancing applications of the gut microbiome. Our top priority is ensuring patient safety from microbiome-based therapeutics, such as FMT. Through the AGA FMT National Registry, AGA is working with physicians and patients to track FMT usage, patient outcomes and adverse events. Associated with the registry is a biorepository of donor and patient stool samples, which will allow further investigation of unexpected events such as those described in FDA’s safety alert.”
Dr. Chen, who received the AGA Research Foundation’s 2016 Research Scholar Award for her work on the gut microbiome and inflammatory bowel disease, pointed out that FMT has also been studied as a way to prevent colonization and infection with certain drug resistant organisms, such as vancomycin-resistant Enterococcus.
“Therefore, it’s not that FMT is ‘bad;’ we just have to be more diligent about optimizing the safety of the procedure by screening for of multidrug-resistant organisms,” she said. “We also need to study the use of FMT more, so that we can fully understand the risks associated with the procedure. It’s an important and potentially lifesaving procedure for some, but it’s important that everyone go into the procedure understanding fully what the risks and benefits are.”
Suspected adverse events related to the administration of FMT products can be reported to the FDA at 1-800-332-1088 or via MedWatch.
Officials at the Food and Drug Administration have issued a safety alert regarding the use of fecal microbiota for transplantation and the risk of serious adverse reactions because of transmission of multidrug-resistant organisms (MDROs).
According to the alert, which was issued on June 13, 2019, the agency became aware of two immunocompromised adult patients who received investigational fecal microbiota for transplantation (FMT) and developed extended-spectrum beta-lactamase (EBSL)–producing Escherichia coli. One of the patients died.
“This is certainly a theoretical risk that we’ve known about,” Lea Ann Chen, MD, a gastroenterologist at New York University, said in an interview. “This announcement is important, because we probably don’t counsel patients specifically about this risk. We say there is a risk for transmission of infectious agents in general, but I think that probably very few counsel patients about a risk for transmission of MDROs.”
The donor stool and FMT used in the two patients were not tested for ESBL-producing gram-negative organisms prior to use.
As a result of these serious adverse reactions, the FDA has determined that the following donor screening and stool testing protections are needed for any investigational use of FMT.
- Donor screening with questions that specifically address risk factors for colonization with MDROs, and exclusion of individuals at higher risk of colonization with MDROs.
- MDRO testing of donor stool and exclusion of stool that tests positive for MDRO. FDA scientists have determined the specific MDRO testing and frequency that should be implemented.
On June 14, the American Gastroenterological Association sent a communication about the FDA alert to its members, which stated that the AGA “is committed to advancing applications of the gut microbiome. Our top priority is ensuring patient safety from microbiome-based therapeutics, such as FMT. Through the AGA FMT National Registry, AGA is working with physicians and patients to track FMT usage, patient outcomes and adverse events. Associated with the registry is a biorepository of donor and patient stool samples, which will allow further investigation of unexpected events such as those described in FDA’s safety alert.”
Dr. Chen, who received the AGA Research Foundation’s 2016 Research Scholar Award for her work on the gut microbiome and inflammatory bowel disease, pointed out that FMT has also been studied as a way to prevent colonization and infection with certain drug resistant organisms, such as vancomycin-resistant Enterococcus.
“Therefore, it’s not that FMT is ‘bad;’ we just have to be more diligent about optimizing the safety of the procedure by screening for of multidrug-resistant organisms,” she said. “We also need to study the use of FMT more, so that we can fully understand the risks associated with the procedure. It’s an important and potentially lifesaving procedure for some, but it’s important that everyone go into the procedure understanding fully what the risks and benefits are.”
Suspected adverse events related to the administration of FMT products can be reported to the FDA at 1-800-332-1088 or via MedWatch.
Officials at the Food and Drug Administration have issued a safety alert regarding the use of fecal microbiota for transplantation and the risk of serious adverse reactions because of transmission of multidrug-resistant organisms (MDROs).
According to the alert, which was issued on June 13, 2019, the agency became aware of two immunocompromised adult patients who received investigational fecal microbiota for transplantation (FMT) and developed extended-spectrum beta-lactamase (EBSL)–producing Escherichia coli. One of the patients died.
“This is certainly a theoretical risk that we’ve known about,” Lea Ann Chen, MD, a gastroenterologist at New York University, said in an interview. “This announcement is important, because we probably don’t counsel patients specifically about this risk. We say there is a risk for transmission of infectious agents in general, but I think that probably very few counsel patients about a risk for transmission of MDROs.”
The donor stool and FMT used in the two patients were not tested for ESBL-producing gram-negative organisms prior to use.
As a result of these serious adverse reactions, the FDA has determined that the following donor screening and stool testing protections are needed for any investigational use of FMT.
- Donor screening with questions that specifically address risk factors for colonization with MDROs, and exclusion of individuals at higher risk of colonization with MDROs.
- MDRO testing of donor stool and exclusion of stool that tests positive for MDRO. FDA scientists have determined the specific MDRO testing and frequency that should be implemented.
On June 14, the American Gastroenterological Association sent a communication about the FDA alert to its members, which stated that the AGA “is committed to advancing applications of the gut microbiome. Our top priority is ensuring patient safety from microbiome-based therapeutics, such as FMT. Through the AGA FMT National Registry, AGA is working with physicians and patients to track FMT usage, patient outcomes and adverse events. Associated with the registry is a biorepository of donor and patient stool samples, which will allow further investigation of unexpected events such as those described in FDA’s safety alert.”
Dr. Chen, who received the AGA Research Foundation’s 2016 Research Scholar Award for her work on the gut microbiome and inflammatory bowel disease, pointed out that FMT has also been studied as a way to prevent colonization and infection with certain drug resistant organisms, such as vancomycin-resistant Enterococcus.
“Therefore, it’s not that FMT is ‘bad;’ we just have to be more diligent about optimizing the safety of the procedure by screening for of multidrug-resistant organisms,” she said. “We also need to study the use of FMT more, so that we can fully understand the risks associated with the procedure. It’s an important and potentially lifesaving procedure for some, but it’s important that everyone go into the procedure understanding fully what the risks and benefits are.”
Suspected adverse events related to the administration of FMT products can be reported to the FDA at 1-800-332-1088 or via MedWatch.
U.S. travelers to Europe need up to date measles immunization
researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.
More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.
France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.
“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.
But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.
Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.
“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”
“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.
In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.
“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.
“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”
Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.
Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.
The statement was funded by the CDC. The authors reported no relevant financial disclosures.
SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.
researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.
More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.
France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.
“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.
But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.
Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.
“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”
“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.
In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.
“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.
“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”
Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.
Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.
The statement was funded by the CDC. The authors reported no relevant financial disclosures.
SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.
researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.
More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.
France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.
“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.
But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.
Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.
“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”
“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.
In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.
“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.
“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”
Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.
Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.
The statement was funded by the CDC. The authors reported no relevant financial disclosures.
SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.
FROM PEDIATRICS
Booster vaccines found largely safe in children on immunosuppressive drugs
MADRID – Administration of live attenuated booster of the MMR vaccine with or without varicella (MMR/V) was not associated with serious adverse events in children on immunosuppressive therapy for a rheumatic disease, according to data presented at the European Congress of Rheumatology.
“The study implies that patients can receive booster vaccinations regardless of age, diagnosis, or therapy,” reported Veronica Bergonzo Moshe, MD, a pediatric rheumatologist at Meir Medical Center, Kfar Saba, Israel.
In the absence of safety data, the vaccination of children with rheumatic diseases taking immunosuppressive therapies has been controversial. Although these children face communicable and sometimes life-threatening diseases without vaccination, many clinicians are not offering this protection because they fear adverse consequences.
Current Paediatric Rheumatology European Society (PReS) guidelines have been equivocal, recommending that vaccines be considered on a “case-by-case basis” in children with a rheumatic disease if they are taking high doses of disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, or any dose of biologics.
“The fear is that a state of immune suppression might decrease response to the vaccine or lead to a flare of the rheumatologic disease,” Dr. Moshe said.
In the retrospective study presented by Dr. Moshe, data were collected on 234 children with rheumatic diseases who received a live attenuated MMR/V booster. The children were drawn from 12 pediatric rheumatology centers in 10 countries.
In this relatively large series, 82% of the children had oligoarticular or polyarticular juvenile idiopathic arthritis (JIA). A range of other rheumatic diseases, including juvenile dermatomyositis, localized scleroderma, and isolated idiopathic uveitis were represented among the remaining patients. All were taking medication, and 48% were in remission.
When broken down by therapy, there were three localized reactions in 110 (2.7%) children who received the booster while on methotrexate. No other adverse events, including disease flare, were observed.
Similarly, six of the seven adverse events observed in 76 (8%) patients who were taking methotrexate plus a tumor necrosis factor (TNF) inhibitor biologic at the time of vaccination were local reactions. Fever was reported in one patient. All of these events were transient.
In the 39 patients taking a TNF inhibitor alone, there was a single case of transient fever. There were no adverse events reported in the three patients vaccinated while on tocilizumab, seven patients while on anakinra, or five patients while on canakinumab.
Following vaccination, there were no signs of symptoms of the diseases that the vaccines are designed to prevent. In the minority of patients who did develop localized reactions or fever in this series, there was no apparent relationship with disease activity, age, or sex when compared to those who did not develop an adverse event.
These retrospective data are not definitive, but they are reassuring, according to Dr. Moshe. A larger prospective study by the PReS vaccination study group is now planned. The issue of leaving children unvaccinated is topical due to the recent outbreaks of measles in the United States.
“We must have clear guidelines on how to deal with the administration of live vaccines in this patient population so that we can provide the safest and most effective practice,” Dr. Moshe said.
These data are a first step.
“This large retrospective study demonstrates that live attenuated booster vaccine is probably safe in children with rheumatic diseases,” said Dr. Moshe, but she deferred to the PReS guidelines in suggesting that the decision to vaccinate still might best be performed on a case-by-case basis.
MADRID – Administration of live attenuated booster of the MMR vaccine with or without varicella (MMR/V) was not associated with serious adverse events in children on immunosuppressive therapy for a rheumatic disease, according to data presented at the European Congress of Rheumatology.
“The study implies that patients can receive booster vaccinations regardless of age, diagnosis, or therapy,” reported Veronica Bergonzo Moshe, MD, a pediatric rheumatologist at Meir Medical Center, Kfar Saba, Israel.
In the absence of safety data, the vaccination of children with rheumatic diseases taking immunosuppressive therapies has been controversial. Although these children face communicable and sometimes life-threatening diseases without vaccination, many clinicians are not offering this protection because they fear adverse consequences.
Current Paediatric Rheumatology European Society (PReS) guidelines have been equivocal, recommending that vaccines be considered on a “case-by-case basis” in children with a rheumatic disease if they are taking high doses of disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, or any dose of biologics.
“The fear is that a state of immune suppression might decrease response to the vaccine or lead to a flare of the rheumatologic disease,” Dr. Moshe said.
In the retrospective study presented by Dr. Moshe, data were collected on 234 children with rheumatic diseases who received a live attenuated MMR/V booster. The children were drawn from 12 pediatric rheumatology centers in 10 countries.
In this relatively large series, 82% of the children had oligoarticular or polyarticular juvenile idiopathic arthritis (JIA). A range of other rheumatic diseases, including juvenile dermatomyositis, localized scleroderma, and isolated idiopathic uveitis were represented among the remaining patients. All were taking medication, and 48% were in remission.
When broken down by therapy, there were three localized reactions in 110 (2.7%) children who received the booster while on methotrexate. No other adverse events, including disease flare, were observed.
Similarly, six of the seven adverse events observed in 76 (8%) patients who were taking methotrexate plus a tumor necrosis factor (TNF) inhibitor biologic at the time of vaccination were local reactions. Fever was reported in one patient. All of these events were transient.
In the 39 patients taking a TNF inhibitor alone, there was a single case of transient fever. There were no adverse events reported in the three patients vaccinated while on tocilizumab, seven patients while on anakinra, or five patients while on canakinumab.
Following vaccination, there were no signs of symptoms of the diseases that the vaccines are designed to prevent. In the minority of patients who did develop localized reactions or fever in this series, there was no apparent relationship with disease activity, age, or sex when compared to those who did not develop an adverse event.
These retrospective data are not definitive, but they are reassuring, according to Dr. Moshe. A larger prospective study by the PReS vaccination study group is now planned. The issue of leaving children unvaccinated is topical due to the recent outbreaks of measles in the United States.
“We must have clear guidelines on how to deal with the administration of live vaccines in this patient population so that we can provide the safest and most effective practice,” Dr. Moshe said.
These data are a first step.
“This large retrospective study demonstrates that live attenuated booster vaccine is probably safe in children with rheumatic diseases,” said Dr. Moshe, but she deferred to the PReS guidelines in suggesting that the decision to vaccinate still might best be performed on a case-by-case basis.
MADRID – Administration of live attenuated booster of the MMR vaccine with or without varicella (MMR/V) was not associated with serious adverse events in children on immunosuppressive therapy for a rheumatic disease, according to data presented at the European Congress of Rheumatology.
“The study implies that patients can receive booster vaccinations regardless of age, diagnosis, or therapy,” reported Veronica Bergonzo Moshe, MD, a pediatric rheumatologist at Meir Medical Center, Kfar Saba, Israel.
In the absence of safety data, the vaccination of children with rheumatic diseases taking immunosuppressive therapies has been controversial. Although these children face communicable and sometimes life-threatening diseases without vaccination, many clinicians are not offering this protection because they fear adverse consequences.
Current Paediatric Rheumatology European Society (PReS) guidelines have been equivocal, recommending that vaccines be considered on a “case-by-case basis” in children with a rheumatic disease if they are taking high doses of disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, or any dose of biologics.
“The fear is that a state of immune suppression might decrease response to the vaccine or lead to a flare of the rheumatologic disease,” Dr. Moshe said.
In the retrospective study presented by Dr. Moshe, data were collected on 234 children with rheumatic diseases who received a live attenuated MMR/V booster. The children were drawn from 12 pediatric rheumatology centers in 10 countries.
In this relatively large series, 82% of the children had oligoarticular or polyarticular juvenile idiopathic arthritis (JIA). A range of other rheumatic diseases, including juvenile dermatomyositis, localized scleroderma, and isolated idiopathic uveitis were represented among the remaining patients. All were taking medication, and 48% were in remission.
When broken down by therapy, there were three localized reactions in 110 (2.7%) children who received the booster while on methotrexate. No other adverse events, including disease flare, were observed.
Similarly, six of the seven adverse events observed in 76 (8%) patients who were taking methotrexate plus a tumor necrosis factor (TNF) inhibitor biologic at the time of vaccination were local reactions. Fever was reported in one patient. All of these events were transient.
In the 39 patients taking a TNF inhibitor alone, there was a single case of transient fever. There were no adverse events reported in the three patients vaccinated while on tocilizumab, seven patients while on anakinra, or five patients while on canakinumab.
Following vaccination, there were no signs of symptoms of the diseases that the vaccines are designed to prevent. In the minority of patients who did develop localized reactions or fever in this series, there was no apparent relationship with disease activity, age, or sex when compared to those who did not develop an adverse event.
These retrospective data are not definitive, but they are reassuring, according to Dr. Moshe. A larger prospective study by the PReS vaccination study group is now planned. The issue of leaving children unvaccinated is topical due to the recent outbreaks of measles in the United States.
“We must have clear guidelines on how to deal with the administration of live vaccines in this patient population so that we can provide the safest and most effective practice,” Dr. Moshe said.
These data are a first step.
“This large retrospective study demonstrates that live attenuated booster vaccine is probably safe in children with rheumatic diseases,” said Dr. Moshe, but she deferred to the PReS guidelines in suggesting that the decision to vaccinate still might best be performed on a case-by-case basis.
REPORTING FROM EULAR 2019 CONGRESS
Rapid assay distinguishes viral from bacterial infection
LJUBLJANA, SLOVENIA – assessing RNA expression of a single patient gene, according to a proof-of-concept study presented by Ruth Barral-Arca at the annual meeting of the European Society for Paediatric Infectious Diseases.
The gene of interest – IFI44L – is entwined in a child’s response to infection. It’s upregulated in the presence of viral infection and suppressed in bacterial infection, explained Ms. Barral-Arca, a PhD student at the University of Santiago de Compostela (Spain).
This investigational real-time PCR assay could provide a major advance over current routine practice, which is to admit a sick febrile child to the hospital, order bacterial cultures, and start parenteral antibiotics presumptively while awaiting the culture results, which usually don’t come back for more than 24 hours. This practice is a step backwards in terms of antibiotic stewardship, because the majority of febrile children have a self-resolving viral infection.
“This is a big problem because a lot of children with viral infections are inappropriately given antibiotics, leading to antimicrobial resistance,” she noted.
Also, misleadingly false-negative bacterial cultures can occur if the causative pathogen wasn’t included in the test, the infection is in a nonaccessible site, or the child has recently been on antibiotics.
All of these shortcomings have led to a new diagnostic strategy based upon measuring the pattern of key host genes upregulated or suppressed during the inflammatory response.
“We’ve seen that, instead of analyzing the bugs, analyzing the host transcriptome response during infection is proving to be a promising tool for disease biomarker identification. And it’s faster. An early differentiation between viral and bacterial patients will help improve triage in emergency departments, decrease the misuse of antibiotics, and guide clinics to a more precise diagnosis. A lot of big hospitals are already doing PCR. They could quickly adopt this kind of analysis,” Ms. Barral-Arca continued.
She presented a pilot study in which the assay was put to the test using multiple blood samples from 14 febrile infants and children up to 6 years of age with microbiologically confirmed bacterial infection, 11 febrile children with confirmed viral infection, and 10 healthy controls.
“I know the numbers seem small, but we did a sample-size power calculation and it’s just fine,” according to the researcher.
The initial study goal was to confirm earlier promising findings from a study of 370 febrile children in the United Kingdom, Spain, and the United States, conducted by the Immunopathology of Respiratory, Inflammatory and Infectious Disease Study (IRIS) Consortium, a study in which several of Ms. Barral-Arca’s senior coinvestigators participated. The IRIS investigators demonstrated that the combined expression pattern of two genes – IFI44L and FAM89A – distinguished the bacterial from viral infections with impressive sensitivity and specificity (JAMA. 2016 Aug 23-30;316[8]:835-45).
The two-gene signature performed similarly well in Ms. Barral-Arca’s study. However, when she and her coinvestigators tested the discriminatory power of the two genes individually, they got a surprise: The real-time PCR analysis assessing expression of IFI44L alone performed even better than the two-gene combination, discriminating viral from bacterial infections with 91% sensitivity, 93% specificity, and an area under the curve of 94%. In contrast, the two-gene signature based upon IFI44L and FAM89A had a sensitivity of 91%, a specificity of 86%, and an area under the curve of 92%. While those differences in performance are small, a single-gene assay saves time, work, and cost, according to Ms. Barral-Arca.
Her group then validated their findings regarding the performance of the IFI44L single-gene signature in two independent cohorts: stored blood samples from the children in the earlier IRIS study, and a group of children with diarrhea of viral or bacterial etiology.
“One gene seems to be enough,” she said. “We have demonstrated in a real-life scenario that host gene expression microarray data can be successfully translated into a fast, highly accurate, and relatively inexpensive in vitro assay that could be implemented in the clinical routine.”
Planned future work includes investigation of how the gene expression evolves over time from fever onset, the possible utility of the assay in noninfectious febrile illnesses such as rheumatoid arthritis, and whether the test discriminates viral from bacterial infection in adults.
Ms. Barral-Arca reported having no financial conflicts regarding her study, supported by institutional funding.
LJUBLJANA, SLOVENIA – assessing RNA expression of a single patient gene, according to a proof-of-concept study presented by Ruth Barral-Arca at the annual meeting of the European Society for Paediatric Infectious Diseases.
The gene of interest – IFI44L – is entwined in a child’s response to infection. It’s upregulated in the presence of viral infection and suppressed in bacterial infection, explained Ms. Barral-Arca, a PhD student at the University of Santiago de Compostela (Spain).
This investigational real-time PCR assay could provide a major advance over current routine practice, which is to admit a sick febrile child to the hospital, order bacterial cultures, and start parenteral antibiotics presumptively while awaiting the culture results, which usually don’t come back for more than 24 hours. This practice is a step backwards in terms of antibiotic stewardship, because the majority of febrile children have a self-resolving viral infection.
“This is a big problem because a lot of children with viral infections are inappropriately given antibiotics, leading to antimicrobial resistance,” she noted.
Also, misleadingly false-negative bacterial cultures can occur if the causative pathogen wasn’t included in the test, the infection is in a nonaccessible site, or the child has recently been on antibiotics.
All of these shortcomings have led to a new diagnostic strategy based upon measuring the pattern of key host genes upregulated or suppressed during the inflammatory response.
“We’ve seen that, instead of analyzing the bugs, analyzing the host transcriptome response during infection is proving to be a promising tool for disease biomarker identification. And it’s faster. An early differentiation between viral and bacterial patients will help improve triage in emergency departments, decrease the misuse of antibiotics, and guide clinics to a more precise diagnosis. A lot of big hospitals are already doing PCR. They could quickly adopt this kind of analysis,” Ms. Barral-Arca continued.
She presented a pilot study in which the assay was put to the test using multiple blood samples from 14 febrile infants and children up to 6 years of age with microbiologically confirmed bacterial infection, 11 febrile children with confirmed viral infection, and 10 healthy controls.
“I know the numbers seem small, but we did a sample-size power calculation and it’s just fine,” according to the researcher.
The initial study goal was to confirm earlier promising findings from a study of 370 febrile children in the United Kingdom, Spain, and the United States, conducted by the Immunopathology of Respiratory, Inflammatory and Infectious Disease Study (IRIS) Consortium, a study in which several of Ms. Barral-Arca’s senior coinvestigators participated. The IRIS investigators demonstrated that the combined expression pattern of two genes – IFI44L and FAM89A – distinguished the bacterial from viral infections with impressive sensitivity and specificity (JAMA. 2016 Aug 23-30;316[8]:835-45).
The two-gene signature performed similarly well in Ms. Barral-Arca’s study. However, when she and her coinvestigators tested the discriminatory power of the two genes individually, they got a surprise: The real-time PCR analysis assessing expression of IFI44L alone performed even better than the two-gene combination, discriminating viral from bacterial infections with 91% sensitivity, 93% specificity, and an area under the curve of 94%. In contrast, the two-gene signature based upon IFI44L and FAM89A had a sensitivity of 91%, a specificity of 86%, and an area under the curve of 92%. While those differences in performance are small, a single-gene assay saves time, work, and cost, according to Ms. Barral-Arca.
Her group then validated their findings regarding the performance of the IFI44L single-gene signature in two independent cohorts: stored blood samples from the children in the earlier IRIS study, and a group of children with diarrhea of viral or bacterial etiology.
“One gene seems to be enough,” she said. “We have demonstrated in a real-life scenario that host gene expression microarray data can be successfully translated into a fast, highly accurate, and relatively inexpensive in vitro assay that could be implemented in the clinical routine.”
Planned future work includes investigation of how the gene expression evolves over time from fever onset, the possible utility of the assay in noninfectious febrile illnesses such as rheumatoid arthritis, and whether the test discriminates viral from bacterial infection in adults.
Ms. Barral-Arca reported having no financial conflicts regarding her study, supported by institutional funding.
LJUBLJANA, SLOVENIA – assessing RNA expression of a single patient gene, according to a proof-of-concept study presented by Ruth Barral-Arca at the annual meeting of the European Society for Paediatric Infectious Diseases.
The gene of interest – IFI44L – is entwined in a child’s response to infection. It’s upregulated in the presence of viral infection and suppressed in bacterial infection, explained Ms. Barral-Arca, a PhD student at the University of Santiago de Compostela (Spain).
This investigational real-time PCR assay could provide a major advance over current routine practice, which is to admit a sick febrile child to the hospital, order bacterial cultures, and start parenteral antibiotics presumptively while awaiting the culture results, which usually don’t come back for more than 24 hours. This practice is a step backwards in terms of antibiotic stewardship, because the majority of febrile children have a self-resolving viral infection.
“This is a big problem because a lot of children with viral infections are inappropriately given antibiotics, leading to antimicrobial resistance,” she noted.
Also, misleadingly false-negative bacterial cultures can occur if the causative pathogen wasn’t included in the test, the infection is in a nonaccessible site, or the child has recently been on antibiotics.
All of these shortcomings have led to a new diagnostic strategy based upon measuring the pattern of key host genes upregulated or suppressed during the inflammatory response.
“We’ve seen that, instead of analyzing the bugs, analyzing the host transcriptome response during infection is proving to be a promising tool for disease biomarker identification. And it’s faster. An early differentiation between viral and bacterial patients will help improve triage in emergency departments, decrease the misuse of antibiotics, and guide clinics to a more precise diagnosis. A lot of big hospitals are already doing PCR. They could quickly adopt this kind of analysis,” Ms. Barral-Arca continued.
She presented a pilot study in which the assay was put to the test using multiple blood samples from 14 febrile infants and children up to 6 years of age with microbiologically confirmed bacterial infection, 11 febrile children with confirmed viral infection, and 10 healthy controls.
“I know the numbers seem small, but we did a sample-size power calculation and it’s just fine,” according to the researcher.
The initial study goal was to confirm earlier promising findings from a study of 370 febrile children in the United Kingdom, Spain, and the United States, conducted by the Immunopathology of Respiratory, Inflammatory and Infectious Disease Study (IRIS) Consortium, a study in which several of Ms. Barral-Arca’s senior coinvestigators participated. The IRIS investigators demonstrated that the combined expression pattern of two genes – IFI44L and FAM89A – distinguished the bacterial from viral infections with impressive sensitivity and specificity (JAMA. 2016 Aug 23-30;316[8]:835-45).
The two-gene signature performed similarly well in Ms. Barral-Arca’s study. However, when she and her coinvestigators tested the discriminatory power of the two genes individually, they got a surprise: The real-time PCR analysis assessing expression of IFI44L alone performed even better than the two-gene combination, discriminating viral from bacterial infections with 91% sensitivity, 93% specificity, and an area under the curve of 94%. In contrast, the two-gene signature based upon IFI44L and FAM89A had a sensitivity of 91%, a specificity of 86%, and an area under the curve of 92%. While those differences in performance are small, a single-gene assay saves time, work, and cost, according to Ms. Barral-Arca.
Her group then validated their findings regarding the performance of the IFI44L single-gene signature in two independent cohorts: stored blood samples from the children in the earlier IRIS study, and a group of children with diarrhea of viral or bacterial etiology.
“One gene seems to be enough,” she said. “We have demonstrated in a real-life scenario that host gene expression microarray data can be successfully translated into a fast, highly accurate, and relatively inexpensive in vitro assay that could be implemented in the clinical routine.”
Planned future work includes investigation of how the gene expression evolves over time from fever onset, the possible utility of the assay in noninfectious febrile illnesses such as rheumatoid arthritis, and whether the test discriminates viral from bacterial infection in adults.
Ms. Barral-Arca reported having no financial conflicts regarding her study, supported by institutional funding.
REPORTING FROM ESPID 2019
Key clinical point: A novel real-time single-gene–expression PCR test quickly distinguishes viral from bacterial infection in febrile children.
Major finding: The expression signature of the IFI44L gene rapidly distinguished bacterial from viral infection in febrile children with 91% sensitivity and 93% specificity.
Study details: This translational study included 25 febrile children with definite bacterial or viral infections and 10 healthy controls.
Disclosures: The presenter reported having no financial conflicts regarding her study, supported by institutional funding.
Get patients vaccinated: Avoid unwelcome international travel souvenirs
Summer officially began June 21, 2019, but many of your patients already may have departed or will soon be headed to international destinations. Reasons for travel are as variable as their destinations and include but are not limited to family vacations, mission trips, study abroad, parental job relocation, and visiting friends and relatives. The majority of the trips are planned at least 3 months in advance; however, for many travelers and their parents, they suddenly get an aha moment and realize there is/are specific vaccines required to obtain a visa or entry to their final destination. Unfortunately, too much emphasis is focused on required vaccines. The well-informed traveler knows that they may be exposed to multiple diseases and many are vaccine preventable.
The accompanying table lists vaccines traditionally considered to be travel vaccines. Several require multiple doses administered over 21-28 days to provide protection. Others such as cholera and yellow fever must be completed at least 10 days prior to departure to be effective. Typhoid has two formulations: The oral and injectable typhoid vaccines should be completed 1 and 2 weeks, respectively, prior to travel. Several vaccines have age limitations. Routine immunization of all infants against hepatitis A was recommended in 2006. Depending on your region, there may be adolescents who have not been immunized. Fortunately, hepatitis A vaccine works immediately.
One of the challenges you face is identifying someone in your area that provides travel medicine advice and immunizations to children and adolescents. Most children and teens travel with their parents, but today many adolescents travel independently with organized groups. Most of the vaccines listed are not routinely administered at your office, yet you most likely will be the first call a parent makes seeking travel advice.
Let me tell you about a few vaccines in particular.
Japanese encephalitis
This is most common cause of encephalitis in Asia and parts of the western Pacific. Risk generally is limited to rural agricultural areas where the causative virus is transmitted by a mosquito. Fatality rates are 20%-30%. Among survivors, 30%-50% have significant neurologic, cognitive, and psychiatric sequelae. Candidates for this vaccine are long-term travelers and short-term travelers with extensive outdoor rural activities.
Meningococcal conjugate vaccines (MCV4)
All travelers to the Hajj Pilgrimage (Aug. 9-14, 2019) and/or Umrah must show proof of immunization. Vaccine must be received at least 10 days prior to and no greater than 5 years prior to arrival to Saudi Arabia. Conjugate vaccine must clearly be documented for validity of 5 years. For all health entry requirements, go to www.moh.gov.sa/en/hajj/pages/healthregulations.aspx.
Measles
The Advisory Committee on Immunization Practices recommends all infants 6-11 months old receive one dose of MMR prior to international travel regardless of the destination. This should be followed by two additional countable doses. All persons at least 12 months of age and born after 1956 should receive two doses of MMR at least 28 days apart prior to international travel.
Rabies
Rabies is a viral disease endemic in more than 150 countries with approximately 60,000 fatal cases worldwide each year. Asia and Africa are the areas with the highest risk of exposure, and dogs are the principal hosts. Human rabies is almost always fatal once symptoms develop. Preexposure vaccine is recommended for persons with prolonged and/or remote travel to countries where rabies immunoglobulin is unavailable and the occurrence of animal rabies is high. Post exposure vaccination on days 0 and 3 still would be required.*
Typhoid
A bacterial infection caused by Salmonella enterica serotype Typhi and Paratyphi manifests with fever, headache, abdominal pain, diarrhea, or constipation. When bacteremia occurs, it usually is referred to as enteric fever. It is acquired by consumption of food/water contaminated with human feces. Highest risk areas include Africa, Southern Asia, and Southeast Asia
Yellow fever
Risk is limited to sub-Saharan Africa and the tropical areas of South America. It is transmitted by the bite of an infected mosquito. The vaccine is required for entry into at least 16 countries. In a country where yellow fever is present, persons transiting through for more than 12 hours to reach their final destination may actually cause a change in the entry requirements for the destination country. For example, travel from the United States to Tanzania requires no yellow fever vaccine while travel from the United States to Nairobi (more than 12 hours) to Tanzania requires yellow fever vaccine for entry into Tanzania. Travel sequence and duration is extremely important. Check the Centers for Disease Control and Prevention yellow fever site and/or the consulate for the most up-to-date yellow fever vaccine requirements.
YF-Vax (yellow fever vaccine) produced by Sanofi Pasteur in the United States currently is unavailable. The company is building a new facility, and vaccine will not be available for the remainder of 2019. To assure vaccine for U.S. travelers, Stamaril, a yellow fever vaccine produced by Sanofi Pasteur in France has been made available at more than 250 sites nationwide. Because Stamaril is offered at a limited number of locations, persons in need of vaccine should not delay seeking it. Because of increased demand related to summer travel, travelers in some areas have reported delays of several weeks in scheduling an appointment. To locate a Stamaril site in your area, go to wwwnc.cdc.gov/travel/page/search-for-stamaril-clinics.
There are several other diseases transmitted by mosquitoes and ticks including malaria, dengue, Zika and rickettsial diseases. Vigilant use of mosquito repellents is a must. Prophylactic medication is available for only malaria and should be initiated prior to exposure. Frequency and duration depends on the medication selected.
So how do you assist your patients?
Once you’ve identified a travel medicine facility in your area, encourage them to seek pretravel advice 4-6 weeks prior to international travel and make sure their routine immunizations are up to date. Generally, this is not an issue. One challenge is the early administration of MMR. While most practitioners know that early administration for international travel has been recommended for years, many office staff are accustomed to administration at only the 12 month and 4 year visit. When parents call requesting immunization, they often are informed that is it unnecessary and the appointment denied. This is a challenge, especially when coordination of administration of another live vaccine, such as yellow fever, is planned. Familiarizing all members of the health care team with current vaccine recommendations is critical.
For country-specific information, up-to-date travel alerts, and to locate a travel medicine clinic, visit www.cdc.gov/travel.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Email her at [email protected].
*This article was updated 6/18/2019.
Summer officially began June 21, 2019, but many of your patients already may have departed or will soon be headed to international destinations. Reasons for travel are as variable as their destinations and include but are not limited to family vacations, mission trips, study abroad, parental job relocation, and visiting friends and relatives. The majority of the trips are planned at least 3 months in advance; however, for many travelers and their parents, they suddenly get an aha moment and realize there is/are specific vaccines required to obtain a visa or entry to their final destination. Unfortunately, too much emphasis is focused on required vaccines. The well-informed traveler knows that they may be exposed to multiple diseases and many are vaccine preventable.
The accompanying table lists vaccines traditionally considered to be travel vaccines. Several require multiple doses administered over 21-28 days to provide protection. Others such as cholera and yellow fever must be completed at least 10 days prior to departure to be effective. Typhoid has two formulations: The oral and injectable typhoid vaccines should be completed 1 and 2 weeks, respectively, prior to travel. Several vaccines have age limitations. Routine immunization of all infants against hepatitis A was recommended in 2006. Depending on your region, there may be adolescents who have not been immunized. Fortunately, hepatitis A vaccine works immediately.
One of the challenges you face is identifying someone in your area that provides travel medicine advice and immunizations to children and adolescents. Most children and teens travel with their parents, but today many adolescents travel independently with organized groups. Most of the vaccines listed are not routinely administered at your office, yet you most likely will be the first call a parent makes seeking travel advice.
Let me tell you about a few vaccines in particular.
Japanese encephalitis
This is most common cause of encephalitis in Asia and parts of the western Pacific. Risk generally is limited to rural agricultural areas where the causative virus is transmitted by a mosquito. Fatality rates are 20%-30%. Among survivors, 30%-50% have significant neurologic, cognitive, and psychiatric sequelae. Candidates for this vaccine are long-term travelers and short-term travelers with extensive outdoor rural activities.
Meningococcal conjugate vaccines (MCV4)
All travelers to the Hajj Pilgrimage (Aug. 9-14, 2019) and/or Umrah must show proof of immunization. Vaccine must be received at least 10 days prior to and no greater than 5 years prior to arrival to Saudi Arabia. Conjugate vaccine must clearly be documented for validity of 5 years. For all health entry requirements, go to www.moh.gov.sa/en/hajj/pages/healthregulations.aspx.
Measles
The Advisory Committee on Immunization Practices recommends all infants 6-11 months old receive one dose of MMR prior to international travel regardless of the destination. This should be followed by two additional countable doses. All persons at least 12 months of age and born after 1956 should receive two doses of MMR at least 28 days apart prior to international travel.
Rabies
Rabies is a viral disease endemic in more than 150 countries with approximately 60,000 fatal cases worldwide each year. Asia and Africa are the areas with the highest risk of exposure, and dogs are the principal hosts. Human rabies is almost always fatal once symptoms develop. Preexposure vaccine is recommended for persons with prolonged and/or remote travel to countries where rabies immunoglobulin is unavailable and the occurrence of animal rabies is high. Post exposure vaccination on days 0 and 3 still would be required.*
Typhoid
A bacterial infection caused by Salmonella enterica serotype Typhi and Paratyphi manifests with fever, headache, abdominal pain, diarrhea, or constipation. When bacteremia occurs, it usually is referred to as enteric fever. It is acquired by consumption of food/water contaminated with human feces. Highest risk areas include Africa, Southern Asia, and Southeast Asia
Yellow fever
Risk is limited to sub-Saharan Africa and the tropical areas of South America. It is transmitted by the bite of an infected mosquito. The vaccine is required for entry into at least 16 countries. In a country where yellow fever is present, persons transiting through for more than 12 hours to reach their final destination may actually cause a change in the entry requirements for the destination country. For example, travel from the United States to Tanzania requires no yellow fever vaccine while travel from the United States to Nairobi (more than 12 hours) to Tanzania requires yellow fever vaccine for entry into Tanzania. Travel sequence and duration is extremely important. Check the Centers for Disease Control and Prevention yellow fever site and/or the consulate for the most up-to-date yellow fever vaccine requirements.
YF-Vax (yellow fever vaccine) produced by Sanofi Pasteur in the United States currently is unavailable. The company is building a new facility, and vaccine will not be available for the remainder of 2019. To assure vaccine for U.S. travelers, Stamaril, a yellow fever vaccine produced by Sanofi Pasteur in France has been made available at more than 250 sites nationwide. Because Stamaril is offered at a limited number of locations, persons in need of vaccine should not delay seeking it. Because of increased demand related to summer travel, travelers in some areas have reported delays of several weeks in scheduling an appointment. To locate a Stamaril site in your area, go to wwwnc.cdc.gov/travel/page/search-for-stamaril-clinics.
There are several other diseases transmitted by mosquitoes and ticks including malaria, dengue, Zika and rickettsial diseases. Vigilant use of mosquito repellents is a must. Prophylactic medication is available for only malaria and should be initiated prior to exposure. Frequency and duration depends on the medication selected.
So how do you assist your patients?
Once you’ve identified a travel medicine facility in your area, encourage them to seek pretravel advice 4-6 weeks prior to international travel and make sure their routine immunizations are up to date. Generally, this is not an issue. One challenge is the early administration of MMR. While most practitioners know that early administration for international travel has been recommended for years, many office staff are accustomed to administration at only the 12 month and 4 year visit. When parents call requesting immunization, they often are informed that is it unnecessary and the appointment denied. This is a challenge, especially when coordination of administration of another live vaccine, such as yellow fever, is planned. Familiarizing all members of the health care team with current vaccine recommendations is critical.
For country-specific information, up-to-date travel alerts, and to locate a travel medicine clinic, visit www.cdc.gov/travel.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Email her at [email protected].
*This article was updated 6/18/2019.
Summer officially began June 21, 2019, but many of your patients already may have departed or will soon be headed to international destinations. Reasons for travel are as variable as their destinations and include but are not limited to family vacations, mission trips, study abroad, parental job relocation, and visiting friends and relatives. The majority of the trips are planned at least 3 months in advance; however, for many travelers and their parents, they suddenly get an aha moment and realize there is/are specific vaccines required to obtain a visa or entry to their final destination. Unfortunately, too much emphasis is focused on required vaccines. The well-informed traveler knows that they may be exposed to multiple diseases and many are vaccine preventable.
The accompanying table lists vaccines traditionally considered to be travel vaccines. Several require multiple doses administered over 21-28 days to provide protection. Others such as cholera and yellow fever must be completed at least 10 days prior to departure to be effective. Typhoid has two formulations: The oral and injectable typhoid vaccines should be completed 1 and 2 weeks, respectively, prior to travel. Several vaccines have age limitations. Routine immunization of all infants against hepatitis A was recommended in 2006. Depending on your region, there may be adolescents who have not been immunized. Fortunately, hepatitis A vaccine works immediately.
One of the challenges you face is identifying someone in your area that provides travel medicine advice and immunizations to children and adolescents. Most children and teens travel with their parents, but today many adolescents travel independently with organized groups. Most of the vaccines listed are not routinely administered at your office, yet you most likely will be the first call a parent makes seeking travel advice.
Let me tell you about a few vaccines in particular.
Japanese encephalitis
This is most common cause of encephalitis in Asia and parts of the western Pacific. Risk generally is limited to rural agricultural areas where the causative virus is transmitted by a mosquito. Fatality rates are 20%-30%. Among survivors, 30%-50% have significant neurologic, cognitive, and psychiatric sequelae. Candidates for this vaccine are long-term travelers and short-term travelers with extensive outdoor rural activities.
Meningococcal conjugate vaccines (MCV4)
All travelers to the Hajj Pilgrimage (Aug. 9-14, 2019) and/or Umrah must show proof of immunization. Vaccine must be received at least 10 days prior to and no greater than 5 years prior to arrival to Saudi Arabia. Conjugate vaccine must clearly be documented for validity of 5 years. For all health entry requirements, go to www.moh.gov.sa/en/hajj/pages/healthregulations.aspx.
Measles
The Advisory Committee on Immunization Practices recommends all infants 6-11 months old receive one dose of MMR prior to international travel regardless of the destination. This should be followed by two additional countable doses. All persons at least 12 months of age and born after 1956 should receive two doses of MMR at least 28 days apart prior to international travel.
Rabies
Rabies is a viral disease endemic in more than 150 countries with approximately 60,000 fatal cases worldwide each year. Asia and Africa are the areas with the highest risk of exposure, and dogs are the principal hosts. Human rabies is almost always fatal once symptoms develop. Preexposure vaccine is recommended for persons with prolonged and/or remote travel to countries where rabies immunoglobulin is unavailable and the occurrence of animal rabies is high. Post exposure vaccination on days 0 and 3 still would be required.*
Typhoid
A bacterial infection caused by Salmonella enterica serotype Typhi and Paratyphi manifests with fever, headache, abdominal pain, diarrhea, or constipation. When bacteremia occurs, it usually is referred to as enteric fever. It is acquired by consumption of food/water contaminated with human feces. Highest risk areas include Africa, Southern Asia, and Southeast Asia
Yellow fever
Risk is limited to sub-Saharan Africa and the tropical areas of South America. It is transmitted by the bite of an infected mosquito. The vaccine is required for entry into at least 16 countries. In a country where yellow fever is present, persons transiting through for more than 12 hours to reach their final destination may actually cause a change in the entry requirements for the destination country. For example, travel from the United States to Tanzania requires no yellow fever vaccine while travel from the United States to Nairobi (more than 12 hours) to Tanzania requires yellow fever vaccine for entry into Tanzania. Travel sequence and duration is extremely important. Check the Centers for Disease Control and Prevention yellow fever site and/or the consulate for the most up-to-date yellow fever vaccine requirements.
YF-Vax (yellow fever vaccine) produced by Sanofi Pasteur in the United States currently is unavailable. The company is building a new facility, and vaccine will not be available for the remainder of 2019. To assure vaccine for U.S. travelers, Stamaril, a yellow fever vaccine produced by Sanofi Pasteur in France has been made available at more than 250 sites nationwide. Because Stamaril is offered at a limited number of locations, persons in need of vaccine should not delay seeking it. Because of increased demand related to summer travel, travelers in some areas have reported delays of several weeks in scheduling an appointment. To locate a Stamaril site in your area, go to wwwnc.cdc.gov/travel/page/search-for-stamaril-clinics.
There are several other diseases transmitted by mosquitoes and ticks including malaria, dengue, Zika and rickettsial diseases. Vigilant use of mosquito repellents is a must. Prophylactic medication is available for only malaria and should be initiated prior to exposure. Frequency and duration depends on the medication selected.
So how do you assist your patients?
Once you’ve identified a travel medicine facility in your area, encourage them to seek pretravel advice 4-6 weeks prior to international travel and make sure their routine immunizations are up to date. Generally, this is not an issue. One challenge is the early administration of MMR. While most practitioners know that early administration for international travel has been recommended for years, many office staff are accustomed to administration at only the 12 month and 4 year visit. When parents call requesting immunization, they often are informed that is it unnecessary and the appointment denied. This is a challenge, especially when coordination of administration of another live vaccine, such as yellow fever, is planned. Familiarizing all members of the health care team with current vaccine recommendations is critical.
For country-specific information, up-to-date travel alerts, and to locate a travel medicine clinic, visit www.cdc.gov/travel.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Email her at [email protected].
*This article was updated 6/18/2019.
Crossword: HIV PrEP
How to have ‘the talk’ with vaccine skeptics
LJUBLJANA, SLOVENIA – An effective strategy in helping vaccine skeptics to come around to accepting immunizations for their children is to pivot the conversation away from vaccine safety and focus instead on the disease itself and its potential consequences, Saad B. Omer, MBBS, PhD, asserted at the annual meeting of the European Society for Paediatric Infectious Diseases.
“Why do we cede ground by focusing too much on the vaccine itself? I call it the disease salience approach,” said Dr. Omer, professor of global health, epidemiology, and pediatrics at Emory University in Atlanta.
It’s a strategy guided by developments in social psychology, persuasion theory, and communication theory. But if applied incorrectly, the disease salience approach can backfire, causing behavioral paralysis and an inability to act, he cautioned.
Dr. Omer explained that it’s a matter of framing.
“Always include a solution to promote self-efficacy and response-efficacy. After you inform parents of disease risks, provide them with actions they can take. Now readdress the vaccine, pointing out that this is the single best way to protect yourself and your baby,” he said. “The lesson is that since vaccines are a social norm, reframe nonvaccination as an active act, rather than vaccination as an active act.”
Don’t attempt to wow parents with statistics on how vaccine complication rates are dwarfed by the disease risk if left unvaccinated, he advised. Studies have shown that‘s generally not effective. What actually works is to provide narratives of disease severity.
“We are excellent linguists, but really, really poor statisticians,” Dr. Omer observed.
Is it ethical to talk to parents about disease risks to influence their behavior? Absolutely, in his view.
“We’re not selling toothpaste. We are in the business of life-saving vaccines. And I would submit that if it’s done correctly it’s entirely ethical to talk about the disease, and sometimes even the severe risks of the disease, instead of the vaccine,” said Dr. Omer.
If parents cite a myth about vaccines, it’s necessary to address it head on without lingering on it. But debunking a myth is tricky because people tend to remember negative information they received earlier.
“If you’re going to debunk a myth, clearly label it as a myth in the headline as you introduce it. State why it’s not true. Replace the myth with the best alternative explanation. Think of it like a blank space where the myth used to reside. That space needs to be filled with an alternative explanation or the myth will come back,” Dr. Omer said.
He is a coauthor of a book titled, ‘The Clinician’s Vaccine Safety Resource Guide: Optimizing Prevention of Vaccine-Preventable Diseases Across the Lifespan.’
LJUBLJANA, SLOVENIA – An effective strategy in helping vaccine skeptics to come around to accepting immunizations for their children is to pivot the conversation away from vaccine safety and focus instead on the disease itself and its potential consequences, Saad B. Omer, MBBS, PhD, asserted at the annual meeting of the European Society for Paediatric Infectious Diseases.
“Why do we cede ground by focusing too much on the vaccine itself? I call it the disease salience approach,” said Dr. Omer, professor of global health, epidemiology, and pediatrics at Emory University in Atlanta.
It’s a strategy guided by developments in social psychology, persuasion theory, and communication theory. But if applied incorrectly, the disease salience approach can backfire, causing behavioral paralysis and an inability to act, he cautioned.
Dr. Omer explained that it’s a matter of framing.
“Always include a solution to promote self-efficacy and response-efficacy. After you inform parents of disease risks, provide them with actions they can take. Now readdress the vaccine, pointing out that this is the single best way to protect yourself and your baby,” he said. “The lesson is that since vaccines are a social norm, reframe nonvaccination as an active act, rather than vaccination as an active act.”
Don’t attempt to wow parents with statistics on how vaccine complication rates are dwarfed by the disease risk if left unvaccinated, he advised. Studies have shown that‘s generally not effective. What actually works is to provide narratives of disease severity.
“We are excellent linguists, but really, really poor statisticians,” Dr. Omer observed.
Is it ethical to talk to parents about disease risks to influence their behavior? Absolutely, in his view.
“We’re not selling toothpaste. We are in the business of life-saving vaccines. And I would submit that if it’s done correctly it’s entirely ethical to talk about the disease, and sometimes even the severe risks of the disease, instead of the vaccine,” said Dr. Omer.
If parents cite a myth about vaccines, it’s necessary to address it head on without lingering on it. But debunking a myth is tricky because people tend to remember negative information they received earlier.
“If you’re going to debunk a myth, clearly label it as a myth in the headline as you introduce it. State why it’s not true. Replace the myth with the best alternative explanation. Think of it like a blank space where the myth used to reside. That space needs to be filled with an alternative explanation or the myth will come back,” Dr. Omer said.
He is a coauthor of a book titled, ‘The Clinician’s Vaccine Safety Resource Guide: Optimizing Prevention of Vaccine-Preventable Diseases Across the Lifespan.’
LJUBLJANA, SLOVENIA – An effective strategy in helping vaccine skeptics to come around to accepting immunizations for their children is to pivot the conversation away from vaccine safety and focus instead on the disease itself and its potential consequences, Saad B. Omer, MBBS, PhD, asserted at the annual meeting of the European Society for Paediatric Infectious Diseases.
“Why do we cede ground by focusing too much on the vaccine itself? I call it the disease salience approach,” said Dr. Omer, professor of global health, epidemiology, and pediatrics at Emory University in Atlanta.
It’s a strategy guided by developments in social psychology, persuasion theory, and communication theory. But if applied incorrectly, the disease salience approach can backfire, causing behavioral paralysis and an inability to act, he cautioned.
Dr. Omer explained that it’s a matter of framing.
“Always include a solution to promote self-efficacy and response-efficacy. After you inform parents of disease risks, provide them with actions they can take. Now readdress the vaccine, pointing out that this is the single best way to protect yourself and your baby,” he said. “The lesson is that since vaccines are a social norm, reframe nonvaccination as an active act, rather than vaccination as an active act.”
Don’t attempt to wow parents with statistics on how vaccine complication rates are dwarfed by the disease risk if left unvaccinated, he advised. Studies have shown that‘s generally not effective. What actually works is to provide narratives of disease severity.
“We are excellent linguists, but really, really poor statisticians,” Dr. Omer observed.
Is it ethical to talk to parents about disease risks to influence their behavior? Absolutely, in his view.
“We’re not selling toothpaste. We are in the business of life-saving vaccines. And I would submit that if it’s done correctly it’s entirely ethical to talk about the disease, and sometimes even the severe risks of the disease, instead of the vaccine,” said Dr. Omer.
If parents cite a myth about vaccines, it’s necessary to address it head on without lingering on it. But debunking a myth is tricky because people tend to remember negative information they received earlier.
“If you’re going to debunk a myth, clearly label it as a myth in the headline as you introduce it. State why it’s not true. Replace the myth with the best alternative explanation. Think of it like a blank space where the myth used to reside. That space needs to be filled with an alternative explanation or the myth will come back,” Dr. Omer said.
He is a coauthor of a book titled, ‘The Clinician’s Vaccine Safety Resource Guide: Optimizing Prevention of Vaccine-Preventable Diseases Across the Lifespan.’
EXPERT ANALYSIS FROM ESPID 2019
Scabies rates plummeted with community mass drug administration
MILAN – In a region where scabies is endemic, a , findings that may have implications for future treatment of scabies or other infestations in other regions, dermatologist Margot Whitfield, MD, said at the World Congress of Dermatology.
“Mass drug administration is highly effective and safe in the treatment of endemic scabies,” she said.
Using a strategy of directly observed treatment (DOT) with oral ivermectin or topical permethrin for all residents of two separate island groups in Fiji, Dr. Whitfield, together with epidemiologist Lucia Romani, PhD, both of the University of New South Wales, Sydney, and coinvestigators, demonstrated large and sustained decreases in the rates of scabies and impetigo (N Engl J Med. 2015 Dec 10;373[24]:2305-13).
Across study arms, which included a usual care arm, the baseline rate for scabies ranged from 30% to 40%. With usual care, the rate dropped from 36.6% to 18.8% at the end of 12 months, a relative reduction of 49%. However, the 15.8% prevalence rate 12 months after permethrin DOT (from 41.7%), and the 1.9% rate 12 months after ivermectin DOT (from 32.1%) – reductions of 62% and 94%, respectively – represented much larger decreases, “especially since these reductions were seen without any further interventions,” Dr. Whitfield said. “This was extremely exciting, and a game-changer as far as the management of endemic scabies is concerned.”
At baseline, impetigo rates hovered around 20%-25%, and usual care resulted in a 32% reduction at 12 months. With permethrin DOT, the impetigo rate dropped by 54%; with ivermectin DOT, the impetigo rate dropped by 67%. “The community level of impetigo went down, purely as a result of treating the scabies,” Dr. Whitfield said.
The outcomes of this study, she noted, “have contributed to the global discussion of the treatment of scabies.”
Two years after the mass drug administration (MDA) campaign, scabies prevalence remained much lower than at baseline, with clinical scabies diagnosed in 15.2% of the usual care group, 13.5% of the permethrin group, and just 3.6% of the ivermectin group. “The exciting thing for us was that these levels ... were able to be sustained at 2 years,” Dr. Whitfield noted.
The islands that had received ivermectin saw a continued decline in impetigo prevalence as well: By 24 months, impetigo was seen in 2.6% of participants in that arm.
Scabies is a neglected – but highly treatable – tropical disease, she noted. It is associated with intense pruritus, which results in reduced quality of life, and excoriations predispose those affected to bacterial superinfections, commonly impetigo in the young.
In Fiji, the scabies mite infests nearly 40% of those aged 5-9 years, and over one-third of those younger than 5 years. Rates drop steeply with increasing age and then climb again for the elderly; still, prevalence tops 10% for all Fijian age groups, Dr. Whitfield pointed out. Overall, scabies prevalence is 23% in Fiji, with resultant impetigo affecting 19% of the population.
Providing more details about the study, she said that she and her collaborators – working in conjunction with the Fijian Ministry of Health – took advantage of the geography of the island country, whose 850,000 residents live on 300 islands, to compare mass drug treatment with either ivermectin or permethrin with usual care. “We actually didn’t look for ‘infected scabies,’ ” she explained. “We looked for scabies as one outcome, and infection as another.”
The study was designed to take advantage of lessons from previous public health work addressing filariasis and soil-transmitted helminths, and addressed the following question: In Fiji, could a single round of MDA for scabies control lead to sustained reductions in scabies and impetigo prevalence 12 months later, compared with standard care?
The study applied standard-of-care scabies treatment to residents of one island; here, all residents of the island were assessed for scabies, and those who received a clinical diagnosis of scabies, along with family members and close contacts, were treated. Another group of three small islands received permethrin MDA. A third pair of neighboring islands received ivermectin MDA.
For one MDA arm, island residents received oral ivermectin via DOT. A second DOT dose was administered for those with clinically diagnosed scabies. For pregnant and breastfeeding women, children weighing less than 15 kg, and those with ivermectin hypersensitivity, permethrin was used, Dr. Whitfield said.
The individuals in the permethrin MDA arm received one topical dose via DOT, with a second round of topical permethrin for those with topical scabies.
In all, 803 Fijians were assigned to receive standard of care, 532 permethrin MDA, and 716 ivermectin MDA. Of these, 623 received ivermectin DOT, and 93 received permethrin. In all, DOT was achieved for 96% of those receiving the first dose. At baseline, 230 patients had scabies, with 200 receiving ivermectin and 30 permethrin; the DOT rate was 100% for the second dose.
For the permethrin arm, just 307 of 532 participants (58%) had DOT, though all were given permethrin. Scabies was present at baseline for 222 participants, and of these, 181 had DOT. “It’s much easier to do the direct observed therapy with an oral medication than with a cream,” Dr. Whitfield said. Data were not collected for the Fijians who received usual care at community health centers.
Outcomes were clinically determined via the child skin assessment algorithm of the World Health Organization’s International Management of Childhood Illness (IMCI) guidelines.
Dr. Whitfield acknowledged that the study was not a true cluster-randomized trial, and differences existed between the communities studies. Also, “dermatoscopy was not a practical option” for this real-world trial in a resource-limited setting, but validated clinical criteria were used, she said.
Going forward, she and her colleagues are continuing to track durability of reduced scabies rates, as well as downstream sequelae such as impetigo and septicemia. Also, “we need to see whether this community- and island-based project could be scaled up to a national or regional level,” she said.
The burden of disease from scabies globally is probably underestimated, and changing migration patterns may bring endemic scabies to the doorsteps of more developed nations, prompting consideration of MDA as a strategy in expanded circumstances.
Dr. Whitfield reported that she had no relevant conflicts of interest.
MILAN – In a region where scabies is endemic, a , findings that may have implications for future treatment of scabies or other infestations in other regions, dermatologist Margot Whitfield, MD, said at the World Congress of Dermatology.
“Mass drug administration is highly effective and safe in the treatment of endemic scabies,” she said.
Using a strategy of directly observed treatment (DOT) with oral ivermectin or topical permethrin for all residents of two separate island groups in Fiji, Dr. Whitfield, together with epidemiologist Lucia Romani, PhD, both of the University of New South Wales, Sydney, and coinvestigators, demonstrated large and sustained decreases in the rates of scabies and impetigo (N Engl J Med. 2015 Dec 10;373[24]:2305-13).
Across study arms, which included a usual care arm, the baseline rate for scabies ranged from 30% to 40%. With usual care, the rate dropped from 36.6% to 18.8% at the end of 12 months, a relative reduction of 49%. However, the 15.8% prevalence rate 12 months after permethrin DOT (from 41.7%), and the 1.9% rate 12 months after ivermectin DOT (from 32.1%) – reductions of 62% and 94%, respectively – represented much larger decreases, “especially since these reductions were seen without any further interventions,” Dr. Whitfield said. “This was extremely exciting, and a game-changer as far as the management of endemic scabies is concerned.”
At baseline, impetigo rates hovered around 20%-25%, and usual care resulted in a 32% reduction at 12 months. With permethrin DOT, the impetigo rate dropped by 54%; with ivermectin DOT, the impetigo rate dropped by 67%. “The community level of impetigo went down, purely as a result of treating the scabies,” Dr. Whitfield said.
The outcomes of this study, she noted, “have contributed to the global discussion of the treatment of scabies.”
Two years after the mass drug administration (MDA) campaign, scabies prevalence remained much lower than at baseline, with clinical scabies diagnosed in 15.2% of the usual care group, 13.5% of the permethrin group, and just 3.6% of the ivermectin group. “The exciting thing for us was that these levels ... were able to be sustained at 2 years,” Dr. Whitfield noted.
The islands that had received ivermectin saw a continued decline in impetigo prevalence as well: By 24 months, impetigo was seen in 2.6% of participants in that arm.
Scabies is a neglected – but highly treatable – tropical disease, she noted. It is associated with intense pruritus, which results in reduced quality of life, and excoriations predispose those affected to bacterial superinfections, commonly impetigo in the young.
In Fiji, the scabies mite infests nearly 40% of those aged 5-9 years, and over one-third of those younger than 5 years. Rates drop steeply with increasing age and then climb again for the elderly; still, prevalence tops 10% for all Fijian age groups, Dr. Whitfield pointed out. Overall, scabies prevalence is 23% in Fiji, with resultant impetigo affecting 19% of the population.
Providing more details about the study, she said that she and her collaborators – working in conjunction with the Fijian Ministry of Health – took advantage of the geography of the island country, whose 850,000 residents live on 300 islands, to compare mass drug treatment with either ivermectin or permethrin with usual care. “We actually didn’t look for ‘infected scabies,’ ” she explained. “We looked for scabies as one outcome, and infection as another.”
The study was designed to take advantage of lessons from previous public health work addressing filariasis and soil-transmitted helminths, and addressed the following question: In Fiji, could a single round of MDA for scabies control lead to sustained reductions in scabies and impetigo prevalence 12 months later, compared with standard care?
The study applied standard-of-care scabies treatment to residents of one island; here, all residents of the island were assessed for scabies, and those who received a clinical diagnosis of scabies, along with family members and close contacts, were treated. Another group of three small islands received permethrin MDA. A third pair of neighboring islands received ivermectin MDA.
For one MDA arm, island residents received oral ivermectin via DOT. A second DOT dose was administered for those with clinically diagnosed scabies. For pregnant and breastfeeding women, children weighing less than 15 kg, and those with ivermectin hypersensitivity, permethrin was used, Dr. Whitfield said.
The individuals in the permethrin MDA arm received one topical dose via DOT, with a second round of topical permethrin for those with topical scabies.
In all, 803 Fijians were assigned to receive standard of care, 532 permethrin MDA, and 716 ivermectin MDA. Of these, 623 received ivermectin DOT, and 93 received permethrin. In all, DOT was achieved for 96% of those receiving the first dose. At baseline, 230 patients had scabies, with 200 receiving ivermectin and 30 permethrin; the DOT rate was 100% for the second dose.
For the permethrin arm, just 307 of 532 participants (58%) had DOT, though all were given permethrin. Scabies was present at baseline for 222 participants, and of these, 181 had DOT. “It’s much easier to do the direct observed therapy with an oral medication than with a cream,” Dr. Whitfield said. Data were not collected for the Fijians who received usual care at community health centers.
Outcomes were clinically determined via the child skin assessment algorithm of the World Health Organization’s International Management of Childhood Illness (IMCI) guidelines.
Dr. Whitfield acknowledged that the study was not a true cluster-randomized trial, and differences existed between the communities studies. Also, “dermatoscopy was not a practical option” for this real-world trial in a resource-limited setting, but validated clinical criteria were used, she said.
Going forward, she and her colleagues are continuing to track durability of reduced scabies rates, as well as downstream sequelae such as impetigo and septicemia. Also, “we need to see whether this community- and island-based project could be scaled up to a national or regional level,” she said.
The burden of disease from scabies globally is probably underestimated, and changing migration patterns may bring endemic scabies to the doorsteps of more developed nations, prompting consideration of MDA as a strategy in expanded circumstances.
Dr. Whitfield reported that she had no relevant conflicts of interest.
MILAN – In a region where scabies is endemic, a , findings that may have implications for future treatment of scabies or other infestations in other regions, dermatologist Margot Whitfield, MD, said at the World Congress of Dermatology.
“Mass drug administration is highly effective and safe in the treatment of endemic scabies,” she said.
Using a strategy of directly observed treatment (DOT) with oral ivermectin or topical permethrin for all residents of two separate island groups in Fiji, Dr. Whitfield, together with epidemiologist Lucia Romani, PhD, both of the University of New South Wales, Sydney, and coinvestigators, demonstrated large and sustained decreases in the rates of scabies and impetigo (N Engl J Med. 2015 Dec 10;373[24]:2305-13).
Across study arms, which included a usual care arm, the baseline rate for scabies ranged from 30% to 40%. With usual care, the rate dropped from 36.6% to 18.8% at the end of 12 months, a relative reduction of 49%. However, the 15.8% prevalence rate 12 months after permethrin DOT (from 41.7%), and the 1.9% rate 12 months after ivermectin DOT (from 32.1%) – reductions of 62% and 94%, respectively – represented much larger decreases, “especially since these reductions were seen without any further interventions,” Dr. Whitfield said. “This was extremely exciting, and a game-changer as far as the management of endemic scabies is concerned.”
At baseline, impetigo rates hovered around 20%-25%, and usual care resulted in a 32% reduction at 12 months. With permethrin DOT, the impetigo rate dropped by 54%; with ivermectin DOT, the impetigo rate dropped by 67%. “The community level of impetigo went down, purely as a result of treating the scabies,” Dr. Whitfield said.
The outcomes of this study, she noted, “have contributed to the global discussion of the treatment of scabies.”
Two years after the mass drug administration (MDA) campaign, scabies prevalence remained much lower than at baseline, with clinical scabies diagnosed in 15.2% of the usual care group, 13.5% of the permethrin group, and just 3.6% of the ivermectin group. “The exciting thing for us was that these levels ... were able to be sustained at 2 years,” Dr. Whitfield noted.
The islands that had received ivermectin saw a continued decline in impetigo prevalence as well: By 24 months, impetigo was seen in 2.6% of participants in that arm.
Scabies is a neglected – but highly treatable – tropical disease, she noted. It is associated with intense pruritus, which results in reduced quality of life, and excoriations predispose those affected to bacterial superinfections, commonly impetigo in the young.
In Fiji, the scabies mite infests nearly 40% of those aged 5-9 years, and over one-third of those younger than 5 years. Rates drop steeply with increasing age and then climb again for the elderly; still, prevalence tops 10% for all Fijian age groups, Dr. Whitfield pointed out. Overall, scabies prevalence is 23% in Fiji, with resultant impetigo affecting 19% of the population.
Providing more details about the study, she said that she and her collaborators – working in conjunction with the Fijian Ministry of Health – took advantage of the geography of the island country, whose 850,000 residents live on 300 islands, to compare mass drug treatment with either ivermectin or permethrin with usual care. “We actually didn’t look for ‘infected scabies,’ ” she explained. “We looked for scabies as one outcome, and infection as another.”
The study was designed to take advantage of lessons from previous public health work addressing filariasis and soil-transmitted helminths, and addressed the following question: In Fiji, could a single round of MDA for scabies control lead to sustained reductions in scabies and impetigo prevalence 12 months later, compared with standard care?
The study applied standard-of-care scabies treatment to residents of one island; here, all residents of the island were assessed for scabies, and those who received a clinical diagnosis of scabies, along with family members and close contacts, were treated. Another group of three small islands received permethrin MDA. A third pair of neighboring islands received ivermectin MDA.
For one MDA arm, island residents received oral ivermectin via DOT. A second DOT dose was administered for those with clinically diagnosed scabies. For pregnant and breastfeeding women, children weighing less than 15 kg, and those with ivermectin hypersensitivity, permethrin was used, Dr. Whitfield said.
The individuals in the permethrin MDA arm received one topical dose via DOT, with a second round of topical permethrin for those with topical scabies.
In all, 803 Fijians were assigned to receive standard of care, 532 permethrin MDA, and 716 ivermectin MDA. Of these, 623 received ivermectin DOT, and 93 received permethrin. In all, DOT was achieved for 96% of those receiving the first dose. At baseline, 230 patients had scabies, with 200 receiving ivermectin and 30 permethrin; the DOT rate was 100% for the second dose.
For the permethrin arm, just 307 of 532 participants (58%) had DOT, though all were given permethrin. Scabies was present at baseline for 222 participants, and of these, 181 had DOT. “It’s much easier to do the direct observed therapy with an oral medication than with a cream,” Dr. Whitfield said. Data were not collected for the Fijians who received usual care at community health centers.
Outcomes were clinically determined via the child skin assessment algorithm of the World Health Organization’s International Management of Childhood Illness (IMCI) guidelines.
Dr. Whitfield acknowledged that the study was not a true cluster-randomized trial, and differences existed between the communities studies. Also, “dermatoscopy was not a practical option” for this real-world trial in a resource-limited setting, but validated clinical criteria were used, she said.
Going forward, she and her colleagues are continuing to track durability of reduced scabies rates, as well as downstream sequelae such as impetigo and septicemia. Also, “we need to see whether this community- and island-based project could be scaled up to a national or regional level,” she said.
The burden of disease from scabies globally is probably underestimated, and changing migration patterns may bring endemic scabies to the doorsteps of more developed nations, prompting consideration of MDA as a strategy in expanded circumstances.
Dr. Whitfield reported that she had no relevant conflicts of interest.
EXPERT ANALYSIS FROM WCD2019
CDC activates Emergency Operations Center for Congo Ebola outbreak
in the Democratic Republic of the Congo (DRC). With over 2,000 confirmed cases, the outbreak is the second largest ever recorded.
It recently spread to neighboring Uganda, by a family who crossed the border from the DRC.
As of June 11, 187 CDC staff have completed 278 deployments to the DRC, Uganda, and other neighboring countries, as well as to the World Health Organization in Geneva.
“We are activating the Emergency Operations Center at CDC headquarters to provide enhanced operational support to our” Ebola response team in the Congo. The level 3 activation – the lowest level – “allows the agency to provide increased operational support” and “logistics planning for a longer term, sustained effort,” CDC said in a press release.
Activation “does not mean that the threat of Ebola to the United States has increased.” The risk of global spread remains low, CDC said.
The outbreak is occurring in an area of armed conflict and other problems that complicate public health efforts and increase the risk of disease spread.
in the Democratic Republic of the Congo (DRC). With over 2,000 confirmed cases, the outbreak is the second largest ever recorded.
It recently spread to neighboring Uganda, by a family who crossed the border from the DRC.
As of June 11, 187 CDC staff have completed 278 deployments to the DRC, Uganda, and other neighboring countries, as well as to the World Health Organization in Geneva.
“We are activating the Emergency Operations Center at CDC headquarters to provide enhanced operational support to our” Ebola response team in the Congo. The level 3 activation – the lowest level – “allows the agency to provide increased operational support” and “logistics planning for a longer term, sustained effort,” CDC said in a press release.
Activation “does not mean that the threat of Ebola to the United States has increased.” The risk of global spread remains low, CDC said.
The outbreak is occurring in an area of armed conflict and other problems that complicate public health efforts and increase the risk of disease spread.
in the Democratic Republic of the Congo (DRC). With over 2,000 confirmed cases, the outbreak is the second largest ever recorded.
It recently spread to neighboring Uganda, by a family who crossed the border from the DRC.
As of June 11, 187 CDC staff have completed 278 deployments to the DRC, Uganda, and other neighboring countries, as well as to the World Health Organization in Geneva.
“We are activating the Emergency Operations Center at CDC headquarters to provide enhanced operational support to our” Ebola response team in the Congo. The level 3 activation – the lowest level – “allows the agency to provide increased operational support” and “logistics planning for a longer term, sustained effort,” CDC said in a press release.
Activation “does not mean that the threat of Ebola to the United States has increased.” The risk of global spread remains low, CDC said.
The outbreak is occurring in an area of armed conflict and other problems that complicate public health efforts and increase the risk of disease spread.