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Pediatric pneumococcal conjugate vaccines (PCVs) introduction has directly and indirectly reduced pneumococcal pneumonia and invasive disease caused by PCV-covered serotypes among children and adults globally. In Japan, both PCV7 and PCV13 were introduced into the national immunization program (NIP) for children in 2013. However, the long-term impact of PCV use in children on adult pneumococcal pneumonia in Japan remains unclear.We assessed serotypes isolated from adult pneumococcal pneumonia patients (in- and outpatients) in two multicenter observational studies in Japan: 2011-2014 and 2016-2020. The latter study period was divided into two periods to evaluate changes after PCV introduction in children. The Quellung reaction was used to determine serotypes. We evaluated trends of individual and vaccine-covered serotypes over three periods and assessed the difference in changes by patient group before and after the introduction of pediatric PCVs.A total of 650 patients were enrolled: 224, 322, and 104 in 2011-2014, 2016-2017, and 2018-2020, respectively. The median age was 73 years; 59.7% (388/650) were male; 86.9% (565/650) had comorbidities; and 10.2% (66/650) were nursing-home residents. The proportion of PCV13 serotypes decreased from 52.7% in 2011-2014 to 30.4% in 2016-2017 (p 0.001) after PCV13 introduction for children. However, PCV13, PCV15, and PCV20 serotypes still accounted for 38.5, 43.3, and 59.6% of total pneumococcal pneumonia in 2018-2020, respectively. Decline of PCV13 serotypes was more marked in patients aged ≥65 (-23.5%; p 0.001) than those aged 65 (-12.3%; p = 0.104) from 2011-2014 to 2016-2020. The proportion of PPSV23 non-PCV13 serotypes didn't change over time.The proportion of adult pneumococcal pneumonia caused by PCV13 serotypes in Japan declined after pediatric PCVs introduction into NIP, possibly due to indirect effects of pediatric PCVs. However, use of new PCVs in Japanese adults may potentially prevent additional pneumococcal pneumonia cases. Now, pneumococcal vaccination strategy for older adults requires discussion.

Respiratory rate measurement is one of the core nursing skills for early detection of deterioration of a patient's condition. Nevertheless, it is sometimes bothersome to visually measure respiratory rate over 1 min. Respiratory rate measurement using a mobile phone application "RRate" has been reported to be accurate and completed in a short time. However, it has only been investigated in children. The aim of this study was to validate the "RRate" compared with the 1-min method in adult patients.This was a cross-sectional study in the setting of a nursing school. Videos of the movement of the thorax during respiration of adult patients were made. Nursing students watched these videos and measured respiratory rate with each method. Bland-Altman analysis was used to calculate bias and limits of agreement. The times taken for the measurements were compared using a t test.A total of 59 nursing students participated. When compared to the reference measurement, the one measured using "RRate" and the one measured over 1 min showed a bias of 0.40 breaths per minute and 0.65 breaths per minute, limits of agreement of -2.86 to 3.67 breaths per minute and -2.11 to 3.41 breaths per minute, respectively. The mean measurement time for "RRate" was 22.8 s (95% CI 13.9-36.6), which was significantly shorter than the 65.8 s (95% CI 61.0-73.2) for the measurement over 1 min (p .001).Respiratory rate can be measured accurately in a shorter time using a mobile phone application in adult patients.

The pediatric 13-valent pneumococcal conjugate vaccine (PCV13) was included in the pediatric immunization programme in Japan in late 2013. The impact of vaccination on the serotype distribution and clinical characteristics of pneumococcal pneumonia has not been described.The first phase of this multicentre prospective study was conducted at community-based hospitals in Japan from 2011 to 2014. The second phase was conducted from 2016 to 2017. Pneumococcal isolates and clinical data were collected from patients with community-acquired pneumonia who were ≥15 years of age. Patients were classified by pneumococcal serotype to PCV13 serotype, 23-valent pneumococcal polysaccharide vaccine (PPV23) non-PCV13 serotype, and non-vaccine serotype.A total of 484 patients were enrolled, 241 in the first phase and 243 in the second. The proportion of PCV13 serotypes decreased from 53% to 33% (p 0.001), whereas PPV23 non-PCV13 serotypes did not change (p = 0.754). PCV13 serotypes were associated with increased risk of elevated blood urea nitrogen (adjusted odds ratio 2.49; 95% confidence interval: 1.49-4.16) and hospitalization (adjusted odds ratio 1.74; 95% confidence interval: 1.02-2.95). These associations were not observed in patients with PPV23 non-PCV13 serotypes.The occurrence of pneumococcal pneumonia caused by vaccine-covered serotypes dramatically decreased following the introduction of pediatric PCV13. The PCV13 serotypes were associated with pneumonia severity.

Background Eosinophilic meningitis (EM) is a rare clinical syndrome caused by both infectious and noninfectious diseases. In tropical pacific countries, Angiostrongylus cantonensis is the most common cause. However, the EM definition varies in the literature, and its relation to parasitic meningitis (PM) remains unclear. Methodology/Principal findings Adult and adolescent patients of 13 years old or above with suspected central nervous system (CNS) infections with abnormal CSF findings were prospectively enrolled at a tertiary referral hospital in Hanoi, Vietnam from June 2012 to May 2014. Patients with EM or suspected PM (EM/PM) were defined by the presence of either ≥10% eosinophils or an absolute eosinophil cell counts of ≥10/mm3 in the CSF or blood eosinophilia (>16% of WBCs) without CSF eosinophils. In total 679 patients were enrolled: 7 (1.03%) had ≥10% CSF eosinophilia, 20 (2.95%) had ≥10/mm3 CSF eosinophilia, and 7 (1.03%) had >16% blood eosinophilia. The patients with ≥10% CSF eosinophilia were significantly younger (p = 0.017), had a lower body temperature (p = 0.036) than patients with ≥10/mm3 CSF eosinophilia among whom bacterial pathogens were detected in 72.2% (13/18) of those who were tested by culture and/or PCR. In contrast, the characteristics of the patients with >16% blood eosinophilia resembled those of patients with ≥10% CSF eosinophilia. We further conducted serological tests and real-time PCR to identify A. cantonensis. Serology or real-time PCR was positive in 3 (42.8%) patients with ≥10% CSF eosinophilia and 6 (85.7%) patients with >16% blood eosinophilia without CSF eosinophils but none of patients with ≥10/mm3 CSF eosinophilia. Conclusions The etiology of PM in northern Vietnam is A. cantonensis. The eosinophil percentage is a more reliable predictor of parasitic EM than absolute eosinophil count in the CSF. Patients with PM may present with a high percentage of eosinophils in the peripheral blood but not in the CSF., Author summary Eosinophilic meningitis (EM) is a rare meningitis accompanied by eosinophils in the CSF and caused by multiple etiologies. Angiostrongylus cantonensis, which is a rat lungworm parasite, is the most common cause in tropical Asia. Previous papers have defined EM as CSF eosinophils ≥10% or CSF eosinophils ≥10/mm3. However, the relationship of EM to parasitic meningitis (PM) remains unclear. This prospective study enrolled 679 patients with suspected CNS infection who were admitted to a tertiary referral hospital in Hanoi, Vietnam from June 2012 to May 2014. The characteristics of patients with ≥10% CSF eosinophilia resembled those of patients with >16% blood eosinophilia without CSF eosinophils, whereas those of patients with ≥10/mm3 CSF eosinophilia were comparable with those of patients with typical bacterial meningitis. Serology or real-time PCR for A. cantonensis was positive in 3 out of 7 patients with ≥10% CSF eosinophilia and 6 out of 7 patients with > 16% blood eosinophilia without CSF eosinophils but none of patients with ≥10/mm3 CSF eosinophilia. The percentage, in contrast to the absolute eosinophil count in CSF, is reliable for predicting parasitic EM. Patients with PM may present with eosinophilia in the peripheral blood but not in the CSF.

A woman aged 45 years with a 1.5-year history of violaceous plaques on the forehead and chest presented with fever, weight loss and aggravation of the plaques. Inflammatory markers and interleukin-6 level were elevated, and superficial lymphadenopathies and splenomegaly were identified by CT scan. Immunohistochemical findings of the lymph node and the skin showed polyclonal plasmacytosis and follicular hyperplasia, leading to the diagnosis of idiopathic multicentric Castleman disease (iMCD) after human herpesvirus-8 infection was excluded. The patient was successfully treated with anti-interleukin-6 receptor antibody, tocilizumab, following relapse after prednisolone therapy.Our literature review found 11 case reports of pathologically confirmed iMCD preceded by cutaneous plasmacytosis. The median duration of asymptomatic phase with only skin lesions was 7.5 years, whereas the phase lasted only for 1.5 years in our case. iMCD can develop shortly after asymptomatic cutaneous plasmacytosis. Tocilizumab can be a treatment of choice for this type of iMCD.

Background Mortality prediction of pneumonia by severity scores in patients with multiple underlying health conditions has not fully been investigated. This prospective cohort study is to identify mortality-associated underlying health conditions and to analyse their influence on severity-based pneumonia mortality prediction. Methods Adult patients with community-acquired pneumonia or healthcare-associated pneumonia (HCAP) who visited four community hospitals between September 2011 and January 2013 were enrolled. Candidate underlying health conditions, including demographic and clinical characteristics, were incorporated into the logistic regression models, along with CURB (confusion, elevated urea nitrogen, tachypnoea, and hypotension) score as a measure of disease severity. The areas under the receiver operating characteristic curves (AUROC) of the predictive index based on significant underlying health conditions was compared to that of CURB65 (CURB and age ≥ 65) score or Pneumonia severity index (PSI). Mortality association between disease severity and the number of underlying health conditions was analysed. Results In total 1772 patients were eligible for analysis, of which 140 (7.9%) died within 30 days. Six underlying health conditions were independently associated: home care (adjusted odds ratio, 5.84; 95% confidence interval, CI, 2.28–14.99), recent hospitalization (2.21; 1.36–3.60), age ≥ 85 years (2.15; 1.08–4.28), low body mass index (1.99, 1.25–3.16), neoplastic disease (1.82; 1.17–2.85), and male gender (1.78; 1.16–2.75). The predictive index based on these conditions alone had a significantly or marginally higher AUROC than that based on CURB65 score (0.78 vs 0.66, p = 0.02) or PSI (0.78 vs 0.71, p = 0.05), respectively. Compared to this index, the AUROC of the total score consisting of six underlying health conditions and CURB score (range 0–10) did not improve mortality predictions (p = 0.3). In patients with one or less underlying health conditions, the mortality was discretely associated with severe pneumonia (CURB65 ≥ 3) (risk ratio: 7.24, 95%CI: 3.08–25.13), whereas in patients with 2 or more underlying health conditions, the mortality association with severe pneumonia was not detected (risk ratio: 1.53, 95% CI: 0.94–2.50). Conclusions Mortality prediction based on pneumonia severity scores is highly influenced by the accumulating number of underlying health conditions in an ageing society. The validation using a different cohort is necessary to generalise the conclusion. Electronic supplementary material The online version of this article (10.1186/s12890-018-0648-y) contains supplementary material, which is available to authorized users.

BACKGROUND: Scrub typhus (ST) is a leading cause of non-malarial febrile illness in Southeast Asia, but evidence of its true disease burden is limited because of difficulties of making the clinical diagnosis and lack of adequate diagnostic tests. To describe the epidemiology and clinical characteristics of ST, we conducted an observational study using multiple diagnostic assays at a national tertiary hospital in Hanoi, Vietnam. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 1,127 patients hospitalized with documented fever between June 2012 and May 2013. Overall, 33 (2.9%) patients were diagnosed with ST by PCR and/or screening of ELISA for immunoglobulin M (IgM) with confirmatory tests: 14 (42.4%) were confirmed by indirect immunoperoxidase assay (IIP), and 19 (57.6%) were by IIP and PCR. Living by farming, conjunctival injection, eschar, aspartate aminotransferase elevation, and alanine aminotransferase elevation were significantly associated with ST cases (adjusted odds ratios (aORs): 2.8, 3.07, 48.8, 3.51, and 4.13, respectively), and having a comorbidity and neutrophilia were significantly less common in ST cases (aORs: 0.29 and 0.27, respectively). The majority of the ST cases were not clinically diagnosed with rickettsiosis (72.7%). Dominant IIP reactions against a single antigen were identified in 15 ST cases, whereas indistinguishably high reactions against multiple antigens were seen in 11 ST cases. The most frequently observed dominant IIP reaction was against Karp antigen (eight cases) followed by Gilliam (four cases). The highest diagnostic accuracy of IgM ELISA in acute samples was 78%. In a phylogenetic analysis of the 56-kDa type-specific antigen gene, the majority (14 cases) were located in the Karp-related branch followed by the Gilliam-related (two cases), Kato-related (two cases), and TA763-related clades (one case). CONCLUSIONS/SIGNIFICANCE: Both the clinical and laboratory diagnoses of ST remain challenging at a tertiary hospital. Implementation of both serological and nucleic acid amplification assays covering endemic O. tsutsugamushi strains is essential., PLoS neglected tropical diseases, 13(12), e0007928; 2019

Zoonotic potential of a rat-derived hepatitis E virus (HEV), designated as HEV-C1, remains unknown. To evaluate the risk for HEV-C1 infection in humans, paired sera of 208 hospitalized febrile patients collected from 2001 to 2003 in Hanoi, Vietnam, were examined for IgG antibodies to HEV-C1 and genotype 1 HEV (HEV-1), which is common in humans. IgG antibodies to virus-like particles (VLPs) of HEV-C1 and/or HEV-1 were detected from 99 of the 208 convalescent sera in enzyme-linked immunosorbent assay (ELISA). IgG antibody titers to HEV-C1 antigen in 3 of the 99 sera were more than 8-fold higher than those to HEV-1 antigen. IgM antibodies to HEV-C1 antigen were detected in acute sera from 2 of the 3 patients in ELISA and Western blotting. However, no HEV genome was detected. Clinical information was available for 1 of the 2 patients. Hepatic enzymes, aspartate aminotransferase and alanine aminotransferase, were mildly elevated (156 IU/l and 68 IU/l, respectively), and hepatomegaly was detected by ultrasonography. The patient recovered from the illness after 17 days. These results indicated that HEV-C1 or its variants infect humans in Vietnam and may cause acute febrile illness with mild liver dysfunction.

Background In Western clinical training, formulation of a summary statement (SS) is a core exercise for articulation, evaluation, and improvement of clinical reasoning (CR). In Japanese clinical training, structured guidance in developing CR, including opportunity for SS practice, is uncommon, and the present status of case summarization skills is unclear. We used Virtual Patients (VPs) to explore Japanese junior residents’ SS styles and the effectiveness of VPs on improving SS quality. Methods All first-year junior resident physicians at 4 residency programs (n = 54) were assigned randomized sequences of 5 VP modules, rolled out at 6 day intervals. During each module, participants free-texted a case summary and then reviewed a model summary. Thematic analysis was used to identify SS styles and each SS was categorized accordingly. Frequency of SS styles, and SS CR quality determined by 1) an internally developed Key Feature rubric and 2) demonstration of semantic qualification, were compared across modules. Results Four SS styles were identified: numbered features matched to differential diagnoses, differential diagnoses with supportive comments, feature listing, and narrative summarization. From module #1 to #5, significant increases in the narrative summarization SS style (p = 0.016), SS CR quality score (p = 0.021) and percentage of semantically driven SS (p = 0.003) were observed. Conclusions Our study of Japanese junior residents identified distinct clinical case summary statement styles, and observed adoption of the narrative summarization style and improvement in the CR quality of summary statements during a series of VP cases. Electronic supplementary material The online version of this article (doi:10.1186/s12909-016-0571-y) contains supplementary material, which is available to authorized users.

A descriptive study on rickettsiosis was conducted at the largest referral hospital in Hanoi, Vietnam, to identify epidemiological and clinical characteristics of specific rickettsiosis. Between March 2001 and February 2003, we enrolled 579 patients with acute undifferentiated fever (AUF), excluding patients with malaria, dengue fever, and typhoid fever, and serologically tested for Orientia tsutsugamushi and Rickettsia typhi. Of the patients, 237 (40.9%) and 193 (33.3%) had scrub and murine typhus, respectively, and 149 (25.7%) had neither of them (non-scrub and murine typhus [non-ST/MT]). The proportion of murine typhus was highest among patients living in Hanoi whereas that of scrub typhus was highest in national or regional border areas. The presence of an eschar, dyspnea, hypotension, and lymphadenopathy was significantly associated with a diagnosis of scrub typhus (OR = 46.56, 10.90, 9.01, and 7.92, respectively). Patients with murine typhus were less likely to have these findings but more likely to have myalgia, rash, and relative bradycardia (OR = 1.60, 1.56, and 1.45, respectively). Scrub typhus and murine typhus were shown to be common causes of AUF in northern Vietnam although the occurrence of spotted fever group rickettsiae was not determined. Clinical and epidemiological information may help local clinicians make clinical diagnosis of specific rickettsioses in a resource-limited setting.

Background: The rapid urease test and touch cytology have been used for the rapid detection of Helicobacter pylori infection. Recently, a modified rapid urease (MRU) test, which provides results in 20 min has been available on a commercial basis. To date, few reports have evaluated the accuracy of this test. This study evaluated the sensitivity, specificity, and accuracy of the MRU test and touch cytology to detect H. pylori in relation to the density of H. pylori infection determined semi-quantitatively by using immunohistochemical stains. Methods: Biopsy specimens obtained from a total of 60 patients who underwent endoscopy for evaluation of gastroduodenal diseases were studied by using the MRU test, Giemsa stain for touch smear tissue and histological methods. An immunohistochemical stain was used as a standard, and the density of H. pylori infection was graded according to the number of individual bacteria seen as follows: grade 0 = 0; grade 1+ = 1–9; grade 2+ = 10–29; grade 3+ = 30–99; grade 4+ ≥ 100. The severity of gastritis was evaluated histologically in each specimen and compared with the density of H. pylori infection. Results: The MRU test had an overall sensitivity of 73%, specificity of 100% and accuracy of 85%. The Giemsa stain had a sensitivity of 91%, specificity of 100% and accuracy of 95%. The sensitivities of the MRU test and Giemsa stain decreased in mild H. pylori infection. In the MRU test, the sensitivity was 47% when the density of H. pylori infection was 1+, while 80–100% sensitivities were obtained when the densities of infection were ≥ 2+. With the Giemsa stain, the sensitivity was 80% when the density was 1+, while the sensitivity increased to 100% when the densities were ≥ 2+. The severity of gastritis determined by the Rauws scores showed a positive correlation with the density of H. pylori infection as evaluated by immunohistochemical staining. Conclusions: The MRU test had high sensitivity and specificity for moderate to severe H. pylori infection, but it may result in false-negative results in tests for mild infection. As the MRU test has the advantages of shorter incubation times and low cost, a combination of the MRU test and the Giemsa stain for touch cytology may be the most time- and cost-efficient tests in a clinical setting for the diagnosis of H. pylori infection.