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Streptococcus pneumoniae is one of the leading causes of morbidity and mortality in children under 5. Low-income countries are disproportionally affected and data in these settings are lacking. Effective strategies to control disease include infant immunisation with pneumococcal protein-polysaccharide conjugate vaccines. However, ongoing surveillance of carriage and disease are important to understand the impact of vaccination within communities. This thesis evaluated nasopharyngeal (NP) carriage in 3 generations, following introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the UK. NP carriage was also compared between rural and urban Nepalese children and a novel method of delayed culture and transport was assessed. Finally, the immunogenicity of a 10-valent pneumococcal conjugate vaccine administered in a 2-dose priming schedule without a booster was compared to a 3-dose priming schedule with a booster in Nepalese infants. Key findings include carriage rates in UK children being similar to pre-PCV7 (7 valent pneumococcal conjugate vaccine) carriage rates at 47% with low carriage rates in seen in adults. PCV7 serotypes accounted for 1.5% of carriage isolates in children, 0% in parents and 15.4% in older adults. In Nepalese children carriage was higher in a rural (69.2%) compared to an urban setting (40.9%) and delayed culture and transport using silica desiccant packets (SDP) provided a reliable, albeit underestimated, estimate of carriage. Finally this author demonstrated that following primary immunisation and boosting, there was no difference in immune responses to serotypes 1, 5 and 14 with a 2 dose priming schedule compared to a 3-dose schedule. At 2-4 years of age a significantly higher proportion of vaccinees in the 2+1 group had ≥0·2µg/mL IgG for serotypes 1, 5, 6B and 18C compared to vaccinees in the 3+0 group.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree Master of Medicine in Paediatrics (MMed) Johannesburg 2013 / Introduction Invasive pneumococcal disease, including meningitis, caused by Streptococcus pneumoniae is a major cause of morbidity and mortality world-wide. The introduction of pneumococcal polysaccharide-protein conjugate vaccine (PCV) in the United States has resulted in a reduction in incidence of pneumococcal meningitis. PCV was introduced into the South African expanded programme on immunization (EPI) in 2009. Objective We evaluated the temporal association which the introduction of PCV into the South African EPI had on the incidence of pneumococcal meningitis in children. Methods The study was undertaken in Soweto. All children admitted to Chris Hani Baragwanath Academic Hospital (CHBAH) <14 years of age with meningitis from January 2006 to November 2011 were identified through an electronic database and their microbiological records reviewed to identify the causative bacteria. The results were time framed into two groups: prior to introduction of PCV 1 January 2006 to 31 March 2009 (pre-vaccine era) and post PCV-introduction 1 April 2009 to 30 November 2011 (post-vaccine era). Results 783 patients were admitted with suspected meningitis during the study period, of these 243 (31.0%) met the criteria for bacterial meningitis. The incidence of pneumococcal meningitis was decreasing in the CHBAH in-patient paediatric population by 4.7% per annum prior to the introduction of the vaccine in April 2009. The decline in incidence after PCV introduction accelerated to 18% per annum post-vaccine introduction (P=0.391). In the population most at risk for pneumococcal meningitis, children <1 year of age, the annual reduction in incidence of pneumococcal meningitis accelerated from 1.1% in the pre-vaccine era to 43.4% following PCV introduction (P= 0.011). Conclusions The introduction of PCV resulted in a decline in the incidence of pneumococcal meningitis in all age groups. This decline was most dramatic in the <1 year age group.

M.Med. (Diagnostic Radiology), Faculty of Health Sciences, University of the Witwatersrand, 2011 / Pneumocystis jirovecci pneumonia (PJP) in HIV/AIDS is a significant opportunistic infection. As CD4 counts decrease, so does specificity of chest X-ray (CXR). AIM: To determine the proportion of bronchoscopically proven PJP in HIV infected adults, CD4 counts, CXR signs and compare PJP to TB. METHODS: The proportion of bronchoscopically proven PJP and co-infection was determined. Sensitivity and specificity of CXR for the diagnosis of PJP and TB, and frequency of CXR signs were determined. RESULTS: PJP was present in 26.6% and co-infection 19%. Median CD4 (13 cell/mm3) was significantly lower for PJP patients (p = 0.0089). CXR sensitivity for PJP was 33% and specificity was 100%. Bilateral, multilobar and diffuse disease, bronchopneumonia, nodules and cavitation overlapped for PJP and TB. Unilateral and unilobar disease indicated TB over PJP. Effusions and lymphadenpopathy were not seen with PJP. CONCLUSION: PJP makes up a quarter of indeterminate diagnoses in HIV infected adults. Sensitivity of diagnosis on CXR is low. The CXR diagnosis of TB is made more confidently, but is overcalled. In patients with low CD4 levels, a diagnosis of PJP should be considered as important as TB.

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

Influenza (IV) and pneumococcal polysaccharide vaccination (PPV) may reduce hospitalization and mortality but the effectiveness of these vaccines in older adults (≥65 years) is controversial. This thesis includes seven parts with a total of ten studies studying different aspects regarding IV and PPV in institutionalized older adults - the group with the highest infection-related morbidity and mortality. 　　 　　In Part I, we presented the controversies about effectiveness of influenza and pneumococcal vaccination in institutionalized older adults. 　　 　　In Part II, we studied a retrospective cohort of 1737 older adults showing that nursing home residence is independent risk factor of infection-related mortality and hospitalization. 　　 　　In Part III, the second and third studies were systematic reviews showing that IV and PPV could reduce pneumonia and death.. 　　 　　In Part IV, we evaluated the effectivenss of IV and PPV through prospective cohorts. The fourth study was a prospective cohort study of 1859 institutionalized older adults showing that IV significantly reduced mortality and hospitalization. The fifth study was a prospective cohort study of 532 institutionalized older adults showing that when the IV strain does not match the circulating strain, PPV provided additional protection in reducing mortality. 　　 　　In Part V, the sixth study was a randomized controlled trial of 100 institutionalized older adults showing that intradermal IV has better immunogenicity than intramuscular vaccination without compromising safety. 　　 　　In Part VI, we identified factors that may affect clinical effectiveness of IV. The seventh and eighth studies were prospective cohort studies of 711 institutionalized older adults showing that vaccine efficacy declined with increasing impaired functional status and renal function. 　　 　　In Part VII, we identified determinants of receiving IV and PPV in institutionalized older adults. The ninth study was a cross-sectional study of 155 institutionalized older adults showing that encouragement from nHCWs was a major facilitator of receiving vaccination. The tenth study was a cross-sectional study of 1300 nHCWs showing that 40.2% of nHCWs had encouraged residents to receive vaccination. 　　 　　In conclusion, ten studies from this thesis demonstrated that IV and PPV are effective in preventing hospitalization and reducing mortality in institutionalized older adults. Different strategies in improving its effectivenss and acceptance were suggested. / published_or_final_version / Medicine / Master / Doctor of Medicine

Thesis (M.Sc. in Microbiol.) -- Mahidol University, 1970.

MSc (MED) RESEARCH REPORT UNIVERSITY OF THE WITWATERSRAND, JOHANNESBURG. / The research report represents a study to determine the prevalence of antibiotic-resistance of pneumococcal and their scrotypes in Maputo, Mozambique in children under 5 years of age, who were admitted with pneumonia in the Paediatric Unit at the Hospital Central de Maputo. The children included in the study were from suburbs surrounding central Maputo. [Abbreviated Abstract. Open document to view full version] / AC2017

Source: Masters Abstracts International, Volume: 47-06, page: 3554. Adviser: David W. Smith. Includes bibliographical references.