Makito Yaegashi

Serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumococcal pneumonia in adults aged 65 years or older: a multicentre, prospective, test-negative design study

BACKGROUND The serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal pneumonia has not been established in people aged 65 years or older. We assessed the effectiveness of PPV23 in this population. METHODS For this multicentre, prospective study, we enrolled all individuals aged 65 years or older with community-onset pneumonia who visited four study hospitals in Japan between Sept 28, 2011, and Aug 23, 2014. Streptococcus pneumoniae was isolated from sputum and blood samples, and serotyped by the capsular Quellung method. Sputum samples were further tested by PCR assay to identify pneumococcal DNA, and positive samples were examined for 50 serotypes by a nanofluidic real-time PCR assay. Urine samples were tested by a urinary antigen test. Serotype-specific vaccine effectiveness was estimated using the test-negative design. FINDINGS 2621 eligible patients visited the study hospitals, of whom 585 did not have sputum samples available and were excluded from our analysis. 419 (21%) of 2036 patients were positive for pneumococcal infection (232 by sputum culture, 317 by sputum PCR, 197 by urinary antigen test, and 14 by blood culture). 522 (26%) patients were judged to be vaccinated in the analyses. Effectiveness of PPV23 was 27·4% (95% CI 3·2 to 45·6) against all pneumococcal pneumonia, 33·5% (5·6 to 53·1) against PPV23 serotypes, and 2·0% (-78·9 to 46·3) against non-PPV23 serotypes. Although no significant differences between subgroups were seen, higher protection was noted in people younger than 75 years, women, and individuals with lobar pneumonia or health-care-associated pneumonia. INTERPRETATION PPV23 showed low to moderate effectiveness against vaccine serotype pneumococcal pneumonia in people aged 65 years or older. To improve the current pneumococcal vaccination programme, the variability of PPV23 effectiveness in different groups of older people must be further investigated. FUNDING Pfizer and Nagasaki University.

The low-dose ACTH test in the ICU: Not ready for prime time

Measurements and main results: In each test, serum cortisol levels were measured before (T0) and 30 (T30), 60 (T60), and 90 (T90) mins after corticotropin injection. The maximal increase in cortisol (∆max) was calculated as the difference between T0 and the highest cortisol value at T30, T60, or T90 and considered as adequate if >9 μg/dL (250 nmol/L). Nonresponders to the low dose test had a lower survival rate than responders to both tests (27 vs. 47%, p = .06; Kaplan Meier curves). Interestingly, nonresponders to high-dose test received hydrocortisone treatment and had a similar survival to responders. Multivariable logistic regression disclosed that the response to the combined lowdose test and high-dose test was an independent predictor of survival (odds ratio 28.91, 95% confidence interval 1.81– 462.70, p = .017), whereas basal or maximal cortisol levels in both tests were not. Conclusion

Early Stage Relapsing Polychondritis Diagnosed by Nasal Septum Biopsy

Relapsing polychondritis is a rare inflammation of cartilaginous tissues, the diagnosis of which is usually delayed by a mean period of 2.9 years from symptom onset. We present the case of a 36-year-old man with nasal pain and fever. Physical examination of the nose was grossly unremarkable, but there was significant tenderness of the nasal bridge. Acute sinusitis was initially diagnosed due to thickened left frontal sinus mucosa on computed tomography (CT); however, there was no improvement after antibiotic intake. Repeat CT showed edematous inflammation of the nasal septum; biopsy of this site demonstrated erosion and infiltration of lymphocytes, plasma cells, eosinophils, and neutrophils in the hyaline cartilage. Relapsing polychondritis was confirmed by the modified McAdams criteria and can be diagnosed at an early stage by nasal septum biopsy; it should be considered as a differential diagnosis in patients presenting with nasal symptoms alone or persistent sinus symptoms.

Severe Community-acquired Pneumonia Caused by Acinetobacter baumannii Successfully Treated with the Initial Administration of Meropenem Based on the Sputum Gram Staining Findings: A Case Report

A 62-year-old man with diabetes mellitus and a two-day history of fever and dyspnea presented at our hospital. He was diagnosed with community-acquired pneumonia (CAP), septic shock, and respiratory failure. Sputum Gram staining revealed Gram-negative coccobacilli. Based on the Gram staining findings and history, Acinetobacter baumannii was considered as one of the causative organisms of his CAP. Consequently, he was successfully treated with the initial administration of meropenem. We suggest that A. baumannii should be considered as one of the possible causative organisms of CAP based on a fulminant clinical course, and the presence of Gram-negative coccobacilli.

Effectiveness of inactivated influenza vaccine against laboratory-confirmed influenza pneumonia among adults aged ≥65 years in Japan

Abstract Background The effectiveness of inactivated influenza vaccine (IIV) against laboratory-confirmed influenza pneumonia in older adults remains to be established. Methods Pneumonia patients aged ≥65 years who visited a study hospital in Chiba, Japan, were prospectively enrolled from February 2012 to January 2014. Sputum samples were collected from participants and tested for influenza virus by polymerase chain reaction assays. Influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza pneumonia was estimated by a test-negative design. Results Among a total of 814 pneumonia patients, 42 (5.2%) tested positive for influenza: 40 were positive for influenza A virus, and two were positive for influenza B virus. The IVE against laboratory-confirmed influenza pneumonia was 58.3% (95% confidence interval, 28.8–75.6%). The IVE against influenza pneumonia hospital admission, severe pneumonia, and death was 60.2% (95% CI, 22.8–79.4%), 65.5% (95% CI, 44.3–78.7%), and 71% (95% CI, −62.9% to 94.8%), respectively. In the subgroup analyses, the IVE against influenza pneumonia was higher for patients with immunosuppressive conditions (85.9%; 95% CI, 67.4–93.9%) than for those without (48.7%; 95% CI, 2.7–73%) but did not differ by patients’ statin use status. Conclusion IIV effectively reduces the risk of laboratory-confirmed influenza pneumonia in older adults.

Immunogenicity of simultaneous versus sequential administration of a 23-valent pneumococcal polysaccharide vaccine and a quadrivalent influenza vaccine in older individuals: A randomized, open-label, non-inferiority trial

ABSTRACT It is unclear whether simultaneous administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a quadrivalent influenza vaccine (QIV) produces immunogenicity in older individuals. This study tested the hypothesis that the pneumococcal antibody response elicited by simultaneous administration of PPSV23 and QIV in older individuals is not inferior to that elicited by sequential administration of PPSV23 and QIV. We performed a single-center, randomized, open-label, non-inferiority trial comprising 162 adults aged ≥65 years randomly assigned to either the simultaneous (simultaneous injections of PPSV23 and QIV) or sequential (control; PPSV23 injected 2 weeks after QIV vaccination) groups. Pneumococcal immunoglobulin G (IgG) titers of serotypes 23F, 3, 4, 6B, 14, and 19A were assessed. The primary endpoint was the serotype 23F response rate (a ≥2-fold increase in IgG concentrations 4–6 weeks after PPSV23 vaccination). With the non-inferiority margin set at 20% fewer patients, the response rate of serotype 23F in the simultaneous group (77.8%) was not inferior to that of the sequential group (77.6%; difference, 0.1%; 90% confidence interval, −10.8% to 11.1%). None of the pneumococcal IgG serotype titers were significantly different between the groups 4–6 weeks after vaccination. Simultaneous administration did not show a significant decrease in seroprotection odds ratios for H1N1, H3N2, or B/Phuket influenza strains other than B/Texas. Additionally, simultaneous administration did not increase adverse reactions. Hence, simultaneous administration of PPSV23 and QIV shows an acceptable immunogenicity that is comparable to sequential administration without an increase in adverse reactions. (This study was registered with ClinicalTrials.gov [NCT02592486]).

Distinguishing Japanese Spotted Fever and Scrub Typhus, Central Japan, 2004– 2015

Japanese spotted fever (JSF) and scrub typhus (ST) are endemic to Japan and share similar clinical features. To document the clinical and epidemiologic characteristics that distinguish these 2 rickettsial diseases, during 2004–2015 we recruited 31 JSF patients, 188 ST patients, and 97 nonrickettsial disease patients from the southern Boso Peninsula of Japan. JSF occurred during April–October and ST during November–December. Patients with JSF and ST were significantly older and more likely to reside in wooded areas than were patients with nonrickettsial diseases. Spatial analyses revealed that JSF and ST clusters rarely overlapped. Clinical findings more frequently observed in JSF than in ST patients were purpura, palmar/plantar rash, hyponatremia, organ damage, and delayed defervescence after treatment. Although their clinical features are similar, JSF and ST differ in seasonality, geographic distribution, physical signs, and severity. Because a considerable percentage of patients did not notice rash and eschar, many rickettsial diseases might be underdiagnosed in Japan.

Case Report: Concurrent Sympatric Scrub Typhus and Japanese Spotted Fever in Japan

Scrub typhus and Japanese spotted fever-both rickettsial diseases-are endemic and notifiable in Japan and may cause a fatal outcome without prompt treatment. Here we present the first case of a concurrent sympatric infection of both diseases with grade II evidence. A 67-year-old woman, after a single event of potential exposure to the pathogens, presented with a 12-day history of fever, pharyngeal pain, papulo-erythematous rash, and pronounced fatigue. Her erythematous rash was distributed on her trunk and extremities, palms, and soles and eventually progressed to purpura. Fever persisted until doxycycline was administered on day 12. A significant > 4-fold increase in immunoglobulin G and immunoglobulin M titers against multiple serotypes of Orientia tsutsugamushi and Rickettsia japonica were revealed by indirect immunoperoxidase assays. These clinical and serological data, even in the absence of molecular or isolation evidence, provided grade II evidence that this was a concurrent infection of sympatric scrub typhus and Japanese spotted fever.

Influenza Vaccine Effectiveness Against Influenza-Associated Pneumonia and Pneumococcal Pneumonia in Older Adults: A Prospective Test-Negative Design Study

Abstract Background Studies have shown that influenza vaccines are effective in preventing influenza-associated acute respiratory illnesses in older adults. However, the influenza vaccine effectiveness (IVE) against influenza-associated pneumonia in this age group has not been established. No study has formally investigated the IVE against pneumococcal pneumonia. Methods This study was conducted as part of a multicenter prospective investigation of adult pneumonia by the Adult Pneumonia Study Group-Japan (APSG-J). All community-onset pneumonia patients aged 65 years or older who visited a community-based hospital in Chiba, central Japan were enrolled to the study from December 2012 to January 2014. Sputum samples were tested for 13 viruses and 6 bacteria by multiplex PCR assays. Patients were diagnosed as influenza-associated pneumonia if sputum PCR assays were positive for influenza A or B. Patients were diagnosed as pneumococcal pneumonia if sputum culture yielded pneumococcus, sputum PCR assays were positive for both ply and lytA genes, or a urinary antigen test showed a positive result. Patients were considered vaccinated if they had received at least one dose of seasonal inactivated influenza vaccine in the 12 months before the hospital visit. A test-negative design was applied to estimate the IVE for influenza-associated pneumonia and pneumococcal pneumonia. IVEs were calculated as (1 – odds ratio) × 100%. Results A total of 1044 patients were enrolled to the study. Among them, 49 (4.7%) were influenza-associated pneumonia, and 168 (16.1%) were pneumococcal pneumonia. The adjusted IVE against influenza-associated pneumonia was 57.2% (95% CI, 17.9% to 76.8%). The adjusted IVE against pneumococcal pneumonia was 31.7% (0.6% to 53.1%); the estimate did not change before and after controlling for pneumococcal vaccination history. Conclusion Influenza vaccines effectively prevent influenza-associated pneumonia in older adults. Influenza vaccines are also associated with decreased risk of pneumococcal pneumonia in this age group, while some residual confounding may remain. Disclosures All authors: No reported disclosures.

A case of tracheo-innominate artery fistula successfully treated with endovascular stent of the innominate artery

Tracheo‐innominate artery fistula (TIF) is a rare but life‐threatening complication of tracheostomy. We describe a 44‐year‐old man who was admitted for a pressure ulcer infection with a third tracheostomy in place. He showed massive hemoptysis from the TIF, followed by cardiopulmonary arrest. The cuff of the tube was hyperinflated; however, even a slight movement of the tube resulted in recurrent massive hemorrhage. Thus, an endovascular stent graft was placed. Our case shows that sentinel bleeding may be found prior to TIF, and an endovascular repair can be a lifesaving temporizing option, when the hemorrhage was not controlled by hyperinflating the cuff of the tube.