Neisseria meningitidis infection in humans usually manifests as meningitis and septicemia with skin manifestations. Infections of the respiratory tract with N meningitidis have been documented in the past, but often this organism is not routinely considered in the differential diagnosis of pneumonia. The pathogenic role of N meningitidis in lower respiratory tract infections may be underestimated because its isolation is difficult, particularly when oropharyngeal flora are present. We profile 2 elderly patients with primary meningococcal pneumonia to show the importance of Gram stain and culture in early diagnosis. These modalities helped guide treatment and prophylactic measures.

Treatment of Pseudomonas aeruginosa remains challenging, despite the availability ceftolozane-tazobactam. We report a treatment failure with ceftolozane-tazobactam salvage therapy for pneumonia complicated by lung abscess. Drug resistance, dose selection, and source control are possible contributing factors. Ceftolozane-tazobactam susceptibility testing should precede therapy and consideration should be given to dosing selection.

Background: Community acquired pneumonia causes 5,9% of deaths in elderly South Africans. Mortality rates are increased in those in whom initiation of therapy with an appropriate agent has been delayed. Whereas Mycoplasma pneumoniae and Legionella pneumophila are sensitive to the macrolides or tetracycline, they do not respond to the currently recommended first-line agents for community acquired pneumonia, penicillin or a cephalosporin. It was therefore necessary to assess the prevalence of exposure to these 2 organisms in the elderly in order to determine whether a modification in the recommendations may be justified. Methods: Study population and survey: Subjects were residents of 4 old age homes in Cape Town who were older than 60 years and willing to participate. Written consent was obtained, a demographic and medical history questionnaire was completed, and a sample of blood was drawn. Laboratory methods: The indirect fluorescent antibody tests (Zeus Scientific Inc, New Jersey, USA) were used to detect the presence of antibodies to Mycoplasma pneumoniae and Legionella pneumophila. Results: The participation rate in this study was high, with 88,4% (677/766) taking part. Seropositivity for both of these organisms was low. There were 17 participants (2, 51 %) with antibodies to mycoplasma (IgG only in 8, IgM only in 1, and both IgG and IgM in the remaining 8). Titres were low with only 1 IgM titre of 16, and only 3 IgG titres of 64. Antibodies to Legionella were demonstrated in only 9 participants (1,33%). All these titres were 128 or above. Conclusions: It is concluded that first-line therapy for community acquired pneumonia should adhere to the current guidelines published by the South African Pulmonology Society. There is no indication for the routine use of agents active against Legionella or mycoplasma. Clearly, these antibiotics should be introduced if specific pointers to infection with one of these organisms are found. Because of the low seropositivity rate, the indirect fluorescent antibody test for these 2 agents has a high specificity in this population. This may be of use in making a diagnosis in an acute infection Further studies are required to elucidate the immunological response to these organisms in elderly persons. A further survey should be done to determine the seropositivity rate to these agents in community dwelling elderly.

Objective: The purpose of this study was to investigate pneumonia readmissions of older adults with dementia. Readmission rates and predictive factors of older adults with and without dementia were compared in this study. Subjects: A nationally representative sample of 389,198 discharge records, representing 370,003 patients, was extracted from the 2013 Nationwide Readmission Database. Methods: Descriptive statistics were utilized to describe the demographics of the sample population. Differences between groups were analyzed using chi-square or t test statistics as appropriate. A generalized linear model was used to examine predictive factors for pneumonia readmissions. Results: Older adults with dementia had a readmission rate of 23.52% and were 2.9 times more likely to experience a pneumonia readmission than older adults without dementia. Significant differences in characteristics were found when comparing (a) older adults with and without dementia, (b) older adults with and without dementia who were readmitted, and (c) older adults with dementia who were and were not readmitted. Factors that significantly interacted with dementia included (a) discharge disposition, (b) number of chronic conditions, (c) risk of mortality, and (d) median household income. Conclusions: Classifying older adults with dementia as a high-risk group for pneumonia readmissions is supported by the findings of this study. More over, dementia diagnoses significantly affect discharge disposition, there are characteristic differences among older adults with dementia, and comorbidities and risk of mortality significantly affect pneumonia readmissions. Development of strategies to reduce pneumonia readmissions that are tailored to individuals with dementia should be considered.

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第20288号 / 社医博第77号 / 社新制||医||9(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 川上 浩司, 教授 一山 智, 教授 伊達 洋至 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DGAM

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13220号 / 論医博第2167号 / 新制||医||1033(附属図書館) / (主査)教授 高橋 淳, 教授 宮本 享, 教授 伊佐 正 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

IV. ABSTRACT The human metapneumovirus is a novel paramyxovirus associated with acute respiratory infections in children, adults, elderly and immunocompromised individuals. It has a worldwide distribution and the prevalence range between 1.5% to 25% in individuals with respiratory infections. Based on phylogenetic analysis 2 distinct genetic groups (A and B) that are sub-divided into four subgroups (A1, A2, B1 and B2) have been shown to circulate. Until recently, there was no information on the molecular epidemiology and the clinical characteristics of the hMPV in Africa, including South Africa, a region with a high prevalence of paediatric human immunodeficiency virus type-1 (HIV) infection. The molecular epidemiology and clinical characteristics of the hMPV in South Africa was investigated over a three period (2000-2002) in children hospitalized with lower respiratory tract infection. The children were part of a cohort participating in a phase 3 clinical trial investigating the efficacy of a 9-valent-pneumocococcal protein-polysaccharide conjugate vaccine (PCV). The objectives of the study were: i. to investigate the molecular epidemiology of hMPV in South Africa; ii. characterize the burden of hMPV disease and determine the clinical features of hMPV-LRTI in children infected and not infected by HIV; iii. probe the role of Streptococcus pneumoniae in the pathogenesis of hMPV-LRTI. The overall prevalence of hMPV in children hospitalized with lower respiratory tract infections (LRTI) was 7.4%. The mean age of children with hMPV associated LRTI (hMPV-LRTI) in South Africa was 13.3 months (range 1.4-49.2 months), with HIV infected children being older than children not infected with HIV (mean [range] 17.6 [4.5-44.3] vs. 12.3 [1.4-49.2] months; P=0.007). The incidence of hMPV-LRTI was 5.0 (95%C.I.3.3-7.5) fold greater in HIV infected children (incidence rate: 2 504 [95%C.I. 1 683-3 577] per 100 000) than in HIV uninfected children (incidence rate: 505 [95%C.I. 409-618] per 100 000, P<0.0001). Human metapneumovirus was identified less frequently than RSV but more commonly than other studied respiratory viruses. The double-blind PCV-9 vs. placebo controlled trial was used to probe the role of pneumococcal co-infections contributing to the pathogenesis of severe hMPV-LRTI. The incidence of hospitalization for hMPV-LRTI was reduced by 46% (95%, CI, 25-63; P=0.0002) in PCV-9 vaccinees compared to placebo recipients. This inferred that coinfection with Streptococcus pneumoniae was integral to the pathogenesis of hMPV-LRTI requiring hospitalization. Both groups of the hMPV circulated during the three year period including concurrent circulation of multiple subtypes of the virus. There was a transition from group B to group A subtype virus as the dominant circulating virus over sequential years. Sequence analysis of the two attachment glycoproteins (F and G), showed the F gene protein to be highly conserved, in contrast the attachment protein gene (G protein) was highly variable particularly in the extracellular domain between lineages. Repeat hMPV-LRTI by either homologous or heterologous strains within 3 months of each other suggested that natural infection did not confer complete immunity to hMPV. The present study demonstrated that hMPV is a leading pathogen associated with LRTI among children in Africa and indicated that occult pneumococcal co-infections’ were integral in the pathogenesis of hMPV-LRTI requiring hospitalization. Additionally, this is the first study to have characterized the molecular epidemiology of hMPV in Africa and provides insight as to issues that may exist regarding the design of an hMPV vaccine.

No description available.

Background Machine learning techniques, such as convolutional networks, have shown promise in medical image analysis, including the detection of pediatric pneumonia. However, the interpretability of these models is often lacking, compromising their trustworthiness and acceptance in medical applications. The interpretability of machine learning models in medical applications is crucial for trust and bias identification. Aim The aim is to create a locally interpretable neural network that performs comparably to black-box models while being inherently interpretable, enhancing trust in medical machine learning models. Method An MLP ReLU network is trained with Guangzhou Women and Children's Medical Center pediatric chest x-ray image dataset and utilize Aletheia unwrapper for interpretability. A 5-fold cross-validation assesses the network's performance, measuring accuracy and F1 score. The average accuracy and F1 score are 0.90 and 0.91, respectively. To assessthe interpretability results are compared against a CNN network aided with LIME and SHAP to generate explanations. Results Despite lacking convolutional layers, the MLP network satisfactorily categorizes pneumonia images and explanations align with relevant areas of interest from previous studies. Moreover, by comparing it with a state of the art network aided with LIME and SHAP explanations, the local explanations demonstrate to be consistent within areas of the lungs while the post-hoc alternatives often highlighted areas not relevant for the specific task. Conclusion The developed locally interpretable neural network demonstrates promising performance and interpretability. However, additional research and implementation are required for it to outperform the so-called black box models. In a medical setting, a more accurate model despite the score could be crucial, as it could potentially save more lives, which is the ultimate goal of healthcare.

The rise in antibiotic resistant strains of bacteria has led to the need for new methods of combatting bacterial infection. Since the surfaces of bacteria are covered in uniquely patterned capsular polysaccharides, vaccines targeting these polysaccharides have become a popular field of research for protection against pathogenic bacteria. Though licensed polysaccharide vaccines are commercially available, they lack the efficiency to protect patients that are immunocompromised or at high risk because they elicit T cell independent immune responses, resulting in low-affinity antibodies. To elicit a T cell dependent response and thereby recruit B cells that produce high-affinity antibodies, a vaccine was developed consisting of a short target oligosaccharide antigen of no more than four carbohydrate units, a virus-like particle that the antigen is conjugated to, and an NKT cell adjuvant that recruits T cell help. Previously the vaccine utilized in this work successfully elicited the T cell dependent adaptive immune response desired, and B cells were isolated producing high-affinity antibodies to our specific targets. The previous results were from using tetrasaccharide antigens for serotypes 14 and 3 of Streptococcus pneumonia (Sp). To further optimize this vaccine, disaccharides were tested as minimal epitopes for high-affinity antibody production to specific serotypes of Sp. Four disaccharides were synthesized for serotypes 3, 4, 7F, and 9v, one for each serotype. The synthesis of each disaccharide is described. These disaccharides were tested using the vaccine platform we developed. Reactive B cells were isolated producing high-affinity antibodies to the serotype 3 disaccharide antigen. For the other disaccharides only weak antibody responses were observed.