Akitsugu Furumoto

Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease

To determine the clinical efficacy of combined vaccination with 23-valent pneumococcal vaccine (PV) and influenza vaccine (IV) against pneumonia and acute exacerbation of chronic lung diseases (CLD), we conducted an open-label, randomized, controlled study among 167 adults with CLD over a 2-year period. Subjects were randomly assigned to a PV+IV group (n=87) or an IV group (n=80). The number of patients with CLD experiencing infectious acute exacerbation (P=0.022), but not pneumonia (P=0.284), was significantly lower in the PV+IV group compared with the IV group. When these subjects were divided into subgroups, an additive effect of PV with IV in preventing infectious acute exacerbation was significant only in patients with chronic obstructive pulmonary diseases (P=0.037). In patients with CLD, the Kaplan-Meier survival curves demonstrated a significant difference for infectious acute exacerbation (P=0.016) between the two groups. An additive effect of PV with IV on infectious acute exacerbation was found during the first year after vaccination (P=0.019), but not during the second year (P=0.342), and was associated with serotype-specific immune response in sera of these patients who used PV during the same period.

Induction of opsonophagocytic killing activity with pneumococcal conjugate vaccine in human immunodeficiency virus-infected Ugandan adults.

The levels of IgG determined by ELISA may have limited relevance in human immunodeficiency virus (HIV)-infected adults because of non-functional antibodies. 58 HIV-1-infected and 29 HIV-uninfected Ugandan adults were immunized with conjugate vaccine (CV) followed by polysaccharide vaccine (PV) after a 2-month interval, and the opsonophagocytic killing (OPK) titers against serotype 4 or 14 pneumococcal strains as well as the levels of serotype-specific IgG in sera were determined. Significant increases were found in the OPK titers and IgG levels for both serotypes after CV vaccination irrespective of HIV status. Increases in IgG levels and OPK titers were largely dependent on the CD4(+) cell counts, except for increases in the IgG levels for serotype 4. The proportions with serum OPK titer equal to or greater than 8 were 0-4.3% for serotype 4 and 26.7-42.9% for serotype 14 before vaccination, but the proportions increased up to 43.3-86.2% for serotype 4 and 63.3-96.6% for serotype 14 in all three groups 2 months after CV vaccination. The serum OPK titers remained at levels higher than the pre-vaccination level for at least 8 months after CV vaccination. A single dose of CV could afford some protective immunity in HIV-infected African adults before the introduction of antiretroviral therapy.

Comparative immune responses of patients with chronic pulmonary diseases during the 2-year period after pneumococcal vaccination.

ABSTRACT Antibody responses to a 23-valent pneumococcal vaccine for Streptococcus pneumoniae serotypes 6B, 14, 19F, and 23F in 84 patients with chronic pulmonary diseases over a 2-year period after vaccination were examined by using a third-generation enzyme-linked immunosorbent assay. Of these patients, 28 (31%) were low responders who had developed increases of at least twofold in the levels of serotype-specific immunoglobulin G (IgG) in sera for none of the four serotypes at 1 month after vaccination. Although no specific clinical features of low responders were evident, their prevaccination levels of IgG for all serotypes were higher than those of responders. In responders, the levels of IgG specific for serotypes 14 and 23F in sera were greatly increased 1 month after vaccination and those specific for serotypes 6B and 19F were moderately increased. In contrast, no significant increases in the levels of IgG specific for serotypes 6B, 19F, and 23F in the low responders during the same period were found, but the levels of IgG specific for serotype 14 did increase. Although a rapid decline in the levels of IgG for all serotypes in responders between 1 month and 6 months after vaccination was found, the levels of IgG specific for serotypes 14 and 23F in sera remained higher than the prevaccination levels for at least 2 years after vaccination. These data suggest the need for the revaccination of responders but not low responders among patients with chronic pulmonary diseases. Revaccination as early as 3 years postvaccination is recommended for responders to increase the reduced levels of IgG in sera, especially those specific for the weak vaccine antigens.

Usefulness of the Japanese Respiratory Society guidelines for community pneumonia: a retrospective analysis of community-acquired pneumonia between 2000 and 2002 in a general hospital†

Objective:  The aim of this study was to investigate the causative organisms of community‐acquired pneumonia (CAP) diagnosed between 2000 and 2002 and to evaluate the Japanese Respiratory Society (JRS) guidelines.

Antimicrobial Susceptibility and Genetic Characteristics of Streptococcus pneumoniae Isolates Indicating Possible Nosocomial Transmission Routes in a Community Hospital in Japan

ABSTRACT A clinical study was designed to study Streptococcus pneumoniae isolates recovered from a community hospital in Japan from April 2001 to November 2002. A total of 73 isolates were defined as derived from inpatient, outpatient, and hospital staff groups. The MIC results showed that 20 strains (27.4%) were susceptible to penicillin G, 39 strains (53.4%) had intermediate resistance, and 14 strains (19.2%) had full resistance. Low susceptibility to macrolides was also detected: 32.9%, 32.9%, and 34.2% of all strains were resistant to erythromycin, clarithromycin, and azithromycin, respectively. Thirty strains (41%) were resistant to at least two different kinds of antibiotics. Nineteen disparate serotypes were detected besides two nontypeable strains, and the predominant serotypes were 19F and 23F. Pulsed-field gel electrophoresis (PFGE) pattern A was dominant in the serotype 19F group; this pattern was similar to that of the international clone Taiwan 19F. A total of 10 different patterns were detected in the 23F group and were distinguishable from those of the international clones Spain 23F and Taiwan 23F. Pattern b strains were identified in the same ward, and pattern d strains were found both in patients with nosocomial pneumococcal infections (NPI) and in outpatients. In conclusion, drug-resistant S. pneumoniae was spreading rapidly, especially isolates of the serotype 19F and 23F groups. PFGE data revealed interpatient transmission and suggested that there might be some association between NPI patient strains and outpatient strains.

The relationship between biofilm formations and capsule in Haemophilus influenzae

To evaluate the biofilm formation of non-typeable Haemophilus influenzae (NTHi) and H. influenzae type b (Hib) clinical isolates, we conducted the following study. Serotyping and polymerase chain reaction were performed to identify β-lactamase-negative ampicillin (ABPC)-susceptible (BLNAS), β-lactamase-negative ABPC-resistant (BLNAR), TEM-1 type β-lactamase-producing ABPC-resistant (BLPAR)-NTHi, and Hib. Biofilm formation was investigated by microtiter biofilm assay, as well as visually observation with a scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) in a continuous-flow chamber. As a result, totally 99 strains were investigated, and were classified into 4 groups which were 26 gBLNAS, 22 gBLNAR, 28 gBLPAR-NTHi and 23 Hib strains. The mean OD600 in the microtiter biofilm assay of gBLNAS, gBLNAR, gBLPAR-NTHi, and Hib strains were 0.57, 0.50, 0.34, and 0.08, respectively. NTHi strains were similar in terms of biofilm formations, which were observed by SEM and CLSM. Five Hib strains with the alternated type b cap loci showed significantly increased biofilm production than the other Hib strains. In conclusion, gBLNAS, gBLNAR, and gBLPAR-NTHi strains were more capable to produce biofilms compared to Hib strains. Our data suggested that resistant status may not be a key factor but capsule seemed to play an important role in H. influenzae biofilm formation.

Refractory chylothorax in HIV/AIDS-related disseminated mycobacterial infection

A 38-year-old man presented to a previous hospital in December 2011 with a high fever and acute abdominal pain. He was found to have abdominal lymphadenopathy and was diagnosed with HIV infection. His CD4 count was 25/mm3 and viral load was 490 000 copies/mL. He was transferred to our department for further investigations and treatment. Whole body CT revealed bulky, widespread lymphadenopathy, especially in the abdomen, but no ascites or pleural effusion (figure 1A, B). Stool, bone marrow and an abdominal lymph node specimen were positive for acid-fast bacillus stain. A diagnosis of disseminated non-tuberculous mycobacterial …

Accuracy of High-Throughput Nanofluidic PCR-Based Pneumococcal Serotyping and Quantification Assays Using Sputum Samples for Diagnosing Vaccine Serotype Pneumococcal Pneumonia: Analyses by Composite Diagnostic Standards and Bayesian Latent Class Models

ABSTRACT The lack of reliable diagnostic tests for detecting vaccine serotype pneumococcal pneumonia (VTPP) remains a challenging issue in pneumococcal vaccine studies. This study assessed the performances of high-throughput nanofluidic PCR-based pneumococcal serotyping and quantification assay methods using sputum samples (the nanofluidic sputum quantitative PCR [Sp-qPCR] assay) to diagnose 13-valent pneumococcal conjugate VTPP compared with the performance of the serotype-specific urinary antigen detection (UAD) assay using urine samples. Adult pneumonia patients from Japan were enrolled in this study between September 2012 and August 2014. Sputum samples were subjected to the nanofluidic Sp-qPCR assay, quantitatively cultured, and serotyped by the Quellung reaction (SpQt). Urine samples were tested by the UAD method. The diagnostic performances of these tests were assessed using composite reference standards and Bayesian latent class models (BLCMs). Among 244 total patients, 27 (11.1%) tested positive with the UAD assay, while 16 (6.6%) and 34 (13.9%) tested positive with the SpQt and nanofluidic Sp-qPCR assays, respectively, with a cutoff value of ≥104 DNA copies/ml, which showed the maximum value of the Youden index. Using BLCMs, the estimated prevalence for VTPP was 12.9%, and the nanofluidic Sp-qPCR assay demonstrated the best performance (sensitivity, 90.2%; specificity, 96.9%), followed by UAD (sensitivity, 75.6%; specificity, 97.9%) and SpQt (sensitivity, 45.8%; specificity, 99.5%). However, when a higher cutoff value of ≥107 DNA copies/ml was applied, the performance of UAD became comparable to that of Sp-qPCR. The vaccine serotype-specific pneumococcal DNA load in sputum among UAD-positive patients was 3 logs higher than that among UAD-negative patients (P = 0.036). The nanofluidic Sp-qPCR assay may be accurate and useful for detecting VTPP among adults.

A case series of histoplasmosis patients with elevated serum soluble interleukin-2 receptor levels

Histoplasmosis is a common endemic mycosis that is usually asymptomatic but occasionally results in severe illness. Histoplasmosis and its causative agent, Histoplasma capsulatum, are found worldwide but rarely in Japan. In recent years, however, the number of histoplasmosis patients in Japan has increased. In addition, to our knowledge, there are no previous reports of increased serum soluble interleukin-2 receptor (sIL-2R) levels in patients with histoplasmosis. We report a case series of histoplasmosis in three Japanese temporary workers in Manzanillo, Mexico. All three patients developed a persistent high fever and general fatigue. Laboratory tests showed increased C-reactive protein levels and mild liver dysfunction. All patients also showed increased soluble interleukin-2 receptor (sIL-2R) levels. Chest computed tomography revealed multiple nodules in both lung fields. All patients were positive for serum anti-Histoplasma antibodies, and two patients were positive for Histoplasma on polymerase chain reaction tests. After treatment that included antifungals, their conditions gradually improved and laboratory data normalized. Although one patient developed respiratory failure, this patient recovered with antifungal therapy in combination with methylprednisolone. Serum sIL-2R levels in all patients gradually declined to normal levels, indicating their recovery from Histoplasma infection. From our experience with these patients, sIL-2R levels may be a useful biomarker for patients with histoplasmosis.