published_or_final_version / Medicine / Master / Master of Medical Sciences

Invasive pneumococcal disease (IPD) coursed many deaths worldwide according to World Health Organization. Disease burden of IPD among adults were estimated in western countries. However, relative information is lacking in Asia, which occupies over 60% of global population. The objective of this review is to address the disease burden of IPD among adults in Asian and totally 15 articles was reviewed in this paper. The burden of IPD in Asia among adults is hard to estimate but generally in the high level. The highest case fatality rate was occurred in Taiwan about 30.2% in 2007. The most common antibiotic resistance is penicillin and serotypes among Asian countries is similarly; the most common types are 23F, 3, 6B following by 14, 19F, 4, 18C. The factors affect disease burdens are complexity. In the same time, these reference papers only cover 7 regions or countries among Asian; data from other countries and regions was not enough for analysis. Further study about disease burden of IPD among Asian population in adults is necessarily. / published_or_final_version / Public Health / Master / Master of Public Health

Pneumonia is one of the top causes of deaths in children younger than 5 years of age. According to WHO estimation, globally there are nearly 2 millions young children who die from pneumonia every year, and more than 70% of these deaths occurred in Africa and Southeast Asia. Pneumonia caused by Streptococcus pneumoniae (also called pneumococcus) is a vaccine preventable disease, accounting for 39% of community-acquired pneumonia. There are two types of pneumococcal vaccines that are pneumococcal polysaccharide vaccine (PPV) and pneumococcal conjugate vaccines (PCV). The latter one is routinely advised for children younger than five years. The aims of this paper are to review the global disease burden caused by Streptococcus pneumoniae in children younger than 5 years and to gather vaccine program information globally. For narrative review and policy analysis, WHO websites, other websites of health organizations or institutions, and literatures from Pubmed were reviewed, using key words “children pneumonia”, “Streptococcus pneumoniae”, “pneumonia vaccine”, “pneumococcal conjugate vaccine ”, “PCV-7”, “7-valent PCV”, “PCV-13”, “13-valent PCV”. Numerous literatures have reported that obvious incidence decrease of invasive pneumococcal diseases (IPD) in young children after PCV vaccination. In July 2000 PCV-7 (“7-valent pneumococcal conjugate vaccine”) was incorporated into National Immunization Program (NIP) in United States. Although since then the incidence of IPD caused by vaccine-covered serotypes markedly decreased, those caused by non-vaccine-covered serotypes were found substantially increased. In February 2010, PCV-13 (“13-valent pneumococcal conjugate vaccine”) replaced PCV-7 in NIP in United States. With a wider range of serotypes, PCV-13 was expected to be more effective than PCV-7 in children under 5. Using modeling method, many scholars estimated that PCV-13 was likely to be more cost-effective in reported settings when herd immunity was taken into consideration. Schedule of vaccine was another issue that needs to be investigated. There are three schedules commonly adopted by health authorities: 2 primary doses with 1 booster dose (2p+1), and 3 primary doses with 1 booster (3p+1) or without 1 booster dose (3p+0). In individual report, it seems three schedules were all effective. From result of systematic review, more evidence supported to use 3p+0 schedule (and 3p+1 schedule). However, emerging evidences are in support of 2p+1 schedule tool. WHO recommended both 3p+0 and 2p+1 schedule. If the country with high incidence rate in young infant (less than 32 weeks) 2p+1 schedule may not provide adequate protection for special individual serotype. In addition 2p+1 schedule may also lead to lower antibody level between the second primary dose and the booster dose, but the booster dose could induce higher antibody level, which is important for protecting certain serotypes. Countries should consider local factors and choose suitable vaccine schedule accordingly. In terms of global PCV programs, around 80 countries have already added PCV into their NIP, 58 countries (30%) were planning to introduce the program; nevertheless remaining 51 countries (26%) of countries have no schedule to introduce it yet. Most countries that have implemented PCV programs were western industrialized countries. With support from Global Alliance for Vaccines and Immunization (GAVI), 15 eligible African countries have had routine PCV programs. Comparatively, in Asia, India and China, two countries with the largest population and largest number of IPD cases in the world, have no PCV program to the children. Even industrialized economies like Japan and Taiwan have not implemented yet. Asia was lagging behind for decades. PCV program needs to be prioritized in Asian countries. Asian governments should consider investing more in PCV programs (high-income countries) and/or cooperating with other organizations such as GAVI (low-income countries) to increase the coverage of PCVs in children under 5 and to protect them from pneumococcal diseases. / published_or_final_version / Public Health / Master / Master of Public Health

Objectives: By summarizing and comparing the pattern of invasive pneumococcal disease (IPD) in the 4 areas (namely Hong Kong, other parts of China, United States and Thailand) at different stages of implementation of universal pneumococcal vaccination, a snapshot picture could be obtained to visualize how pneumococcal vaccination has impacted upon various important measures, including the burden of IPD, prevalent serotypes, antimicrobial resistance, risk factors of IPD, to guide us on the next step to optimize our ability to combat against IPD. Methods: To achieve the objective, a systematic search through PubMed, Medline, Cochrane Library, EmBase, CINAHL, and the China Journal Net (for Chinese journal articles to obtain a more comprehensive data for “other parts of mainland) has been performed. Articles were selected according to the inclusion and exclusion criteria, and in straight accordance to the literature search and article retrieval steps as described in the methodology. The quality of the articles was assessed by the STROBE (Strengthening the Reporting of Observational studies in Epidemiology) checklists. Results: In general, there was decline in IPD incidence after PCV vaccination, but the problem of serotype replacement and antimicrobial resistance was still an ongoing problem, which differs geographically. Conclusion: From the above data, we could see the significant impact on PCV on reduction of incidence in IPD as shown in United States, however, it was also very clear that unless development of non-serotype specific vaccine become available to us, we are still facing the problem of serotype replacement and that we need to have regular surveillance, as in the case of United States, to supply the data for timely replacement of new PCV combating the emerging serotypes, such that we would still be in the safe ground. In Hong Kong, the statutory reporting of IPD to Centre for Health and Protection (CHP) has been effective since 2/1/201443, after the start of universal immunization since October 2008, followed by PCV10 in 2009 and PCV13 in December 2011, we seems lacking behind on the surveillance. With the surveillance started by CHP, we hope to understand the Hong Kong situation better and with more published data for our local burden and serotype pattern of IPD. It is interesting to note that the antimicrobial pattern does vary geographically, even in US with universal immunization. This suggests that while PCV was helping us to reduce the penicillin resistant strain, another more important factor – the practice of use of antibiotics- is still operating to effect on the overall antibiotic resistance. The pattern that rural Thailand was having much much less penicillin resistance as compared to urban Bangkok, where antibiotic is more readily available, also supports this explanation. / published_or_final_version / Public Health / Master / Master of Public Health

Uncontrolled oxygen is often administered to breathless patients regardless of whether hypoxaemia is present. In acute exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) this may result in carbon dioxide (CO2) retention and worsening respiratory failure in some patients. In AECOPD the main mechanism is the release of hypoxic pulmonary vasoconstriction and an increase in the physiological dead space to tidal volume ratio (VD/VT). Acute asthma and pneumonia have features in common with AECOPD, namely significant ventilation – perfusion mismatch; and there is the potential for CO2 retention to occur if uncontrolled high concentration oxygen is given. There have been no randomised controlled trials of oxygen therapy in pneumonia and only one in asthma. The potential mechanisms of any change in arterial CO2 that may occur with oxygen therapy in respiratory disorders other than COPD remain uncertain. This thesis presents work from three clinical studies. In two randomised controlled trials, high concentration oxygen was compared to titrated oxygen therapy in patients with either acute severe asthma and suspected community acquired pneumonia. Oxygen was administered for one hour in conjunction with standard medical treatment. Transcutaneous CO2 (PtCO2) was continuously monitored and the number of patients with pre-specified increases in PtCO2 were calculated. The proportion of patients with a rise in PtCO2 4 mmHg was significantly higher in the high concentration oxygen groups of both studies. In the pneumonia study 36/72 (50.0%) vs 11/75 (14.7%) met this endpoint, with a relative risk of 3.4 (95% CI 1.9 to 6.2; P <0.001), and in the asthma study 22/50 (44%) vs 10/53 (18.9%) met this endpoint, with a relative risk of 2.3 (95% CI 1.2 to 4.3; P=0.009). Similarly, a rise in PtCO2 8 mmHg was more common with high concentration oxygen. In the pneumonia study 11/72 (15.3%) vs 2/75 (2.7%) of patients met this endpoint, with a relative risk of 5.7 (95% CI 1.3 to 25.0; P=0.007), and 10/50 (20%) vs 3/53 (5.7%) of asthma patients met this endpoint, with a relative risk of 3.6 (95% CI 1.1 to 12.3; P=0.03). A third study measured the physiological response to 20 minutes of 100% oxygen in chronic severe asthma, with comparison to a group of negative controls (normal subjects) and positive controls (COPD patients). There was a significant rise in PtCO2 of similar magnitude in the asthma and COPD groups compared with the normal controls. The mechanism of the PtCO2 rise was similar in asthma and COPD, with an increase in VD/VT but no change in minute ventilation. These studies demonstrate than uncontrolled high concentration oxygen has the potential to cause CO2 retention in respiratory diseases other than COPD, and that in asthma the mechanism of hypercapnia is similar to that in AECOPD. In acute asthma and community-acquired pneumonia oxygen should be administered only to those patients with evidence of arterial hypoxaemia in a dose that relieves hypoxaemia without causing hyperoxia, thereby achieving the benefits of oxygen therapy while reducing the potential for harm.

<I>Streptococcus pneumoniae</I> is a serious pathogen, responsible for a large proportion of cases of pneumonia, bacteraemia and meningitis. Restriction endonuclease analysis (REA) using <I>Taq </I>I and <I>Hae</I> III was evaluated to analyse the genetic relationships among 51 isolates of <I>S. pneumoniae</I> in four different serotypes. This method was used together with pulsed-field gel electrophoresis (PFGE) in the analysis of clinical isolates of bacteraemic <I>S. pneumoniae</I> in the Grampian region of Scotland during a two year period from 1993-5. A total of 104 isolates were collected, of which 93 were analysed by REA and 94 by PFGE. Sensitivities to eight commonly used antibiotics were determined for 99 isolates, and serotyping was performed by the relevant reference laboratory. Records were available for 92 patients and details of past medical history, primary site of infection and outcome were abstracted. Of the clinical isolates analysed, 1% were fully resistant to penicillin and 12% were resistant to erythromycin. The three most common serotypes were 14(23.5%), 4 (12.2%) and 23F (9.2%). The current vaccine, Pneumovax II, was calculated to provide 99.8% cover for the serotypes isolated. The overall incidence of bacteraemic infection was 10.3 per 100,000 population per year, and the mortality was 21.2%. Both the incidence and mortality increased exponentially with respect to age. In both serotype and clinically based studies, when analysed by REA and PFGE, isolates were primarily grouped into closely associated clusters of single serotypes. Some serotypes, such as 3, 6B and 14, were divided into genetically distinct subgroups. The genetics structure of the population was defined as being primarily clonal with evidence of a serotype change in one instance. An erythromycin resistant serotype 14 clone was described, and later discovered to be of the M phenotype. This clone was significantly associated with bacteraemic disease in the under 5 age group, and was demonstrated to be the current major cause of erythromycin resistance in the U.K.

Pneumocystis is a diverse group of fungi found in the lungs of mammals, and can cause a fatal pneumonia in immunosuppressed humans. The project focussed on two main areas of Pneumocystis biology. The first part investigated the transmission of P. jiroveci between humans and comprised three studies. The first study demonstrated direct transmission between a mother and her infant who had Pneumocystis pneumonia, PCP, contemporaneously. The second investigated transmission of P. jiroveci between health care workers and patients with PCP. P. jiroveci was identified in HCW samples but the genotyping data did not demonstrate direct transmission between the HCW and the patients. The third study examined a representative distribution of P. jiroveci genotypes within a whole human lung and identified two foci of infection. The second main area of research investigated PRT1, a multigene family, encoding a protein with homology to KEX-like proteases. The first part of this study attempted to identify the original single-copy PRT1 gene that encodes the progenitor kexin-like protease. Inconclusive sequence data was obtained. The second part of this study examined regulation of PRT1 gene expression, initially using an assay that characterised the length polymorphisms within the proline rich region of the PRT1 gene. In the complex populations of rat-derived Pneumocystis used it was difficult to distinguish reliable differences between the cDNA (expressed) and genomic DNA proline rich region profiles. Subsequent investigations used simple rat-derived Pneumocystis populations that were derived from inocula of 10 Pneumocystis organisms intratracheally injected into nude rats. The catalytic domain of PRT1 was sequenced from cDNA and genomic copies from each of the five low-dose populations. Two majority sequence types were identified, one genomic and the other cDNA. Three of the populations contained a cDNA majority sequence type, implying that some form of regulation of expression was occurring. This hypothesis was further investigated using a second set of simple populations, hybridisation techniques and 5' RACE.

Thesis (M. Sc.)--University of Adelaide, 1984. / Mounted illus. Includes bibliographical references (leaves 283-317).

Thesis (M. P. H.)--University of Hong Kong, 2006. / Also available in print.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.