Moe H. Kyaw

The Changing Epidemiology of Bacterial Meningitis and Invasive Non-meningitic Bacterial Disease in Scotland During the Period 1983-99

We reviewed population-based laboratory reports of invasive meningococcal, pneumococcal, Haemophilus influenzae, Group B Streptococcus (GBS) and Listeria monocytogenes isolates in order to examine the changing epidemiology of meningitis and invasive non-meningitic disease (INMD) caused by these 5 pathogens in the 2 periods before (1983-91) and after (1992-99) routine use of H. influenzae type B conjugate vaccine (Hib) in Scotland. Neissieria meningitidis was the most common cause of meningitis, accounting for 39.2% of cases of meningitis in 1983-91 and 47% of cases in 1992-99, followed by H. influenzae (31%), Streptococcus pneumoniae (22.4%), GBS (3.9%) and L. monocytogenes (3.5%) in 1983-91 and S. pneumoniae (36.3%), H. influenzae (7.8%), GBS (6.1%) and L. monocytogenes (2.8%) in 1992-99. The important epidemiological features of meningitis and INMD caused by these 5 pathogens between 1983-91 and 1992-99 include: 1. The incidence of bacterial meningitis due to S. pneumoniae and GBS was stable; 2. S. pneumoniae was the predominant cause of INMD in both periods; 3. The incidences of INMD caused by N. meningitidis, GBS and S. pneumoniae increased, by 27%, 55% and 56%, respectively; 4. Decreases in the incidences of bacterial meningitis (by 50%) and INMD (by 50%) due to L. monocytogenes were detected; and 5. There were dramatic reductions in the proportions of bacterial meningitis (by 92%) and INMD (by 56%) due to H. influenzae in vaccinated and non-vaccinated individuals. Continued surveillance is necessary to monitor the disease trend, population at risk, serotype distribution and antimicrobial susceptibility in order to implement appropriate public health interventions against invasive bacterial disease.

Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era: A systematic review and meta-analysis

Background Routine immunisation with pneumococcal conjugate vaccines (PCV7/10/13) has reduced invasive pneumococcal disease (IPD) due to vaccine serotypes significantly. However, an increase in disease due to non-vaccine types, or serotype replacement, has been observed. Serotypes’ individual contributions to IPD play a critical role in determining the overall effects of PCVs. This study examines the distribution of pneumococcal serotypes in children to identify leading serotypes associated with IPD post-PCV introduction. Methods A systematic search was performed to identify studies and surveillance reports (published between 2000 and December 2015) of pneumococcal serotypes causing childhood IPD post-PCV introduction. Serotype data were differentiated based on the PCV administered during the study period: PCV7 or higher valent PCVs (PCV10 or PCV13). Meta-analysis was conducted to estimate the proportional contributions of the most frequent serotypes in childhood IPD in each period. Results We identified 68 studies reporting serotype data among IPD cases in children. We analysed data from 38 studies (14 countries) where PCV7 was administered and 20 (24 countries) where PCV10 or PCV13 have been introduced. Studies reported early and late periods of PCV7 administration (range: 2001∓13). In these settings, serotype 19A was the most predominant cause of childhood IPD, accounting for 21.8% (95%CI 18.6∓25.6) of cases. In countries that have introduced higher valent PCVs, study periods were largely representative of the transition and early years of PCV10 or PCV13. In these studies, the overall serotype-specific contribution of 19A was lower (14.2% 95%CI 11.1∓18.3). Overall, non-PCV13 serotypes contributed to 42.2% (95%CI 36.1∓49.5%) of childhood IPD cases. However, regional differences were noted (57.8% in North America, 71.9% in Europe, 45.9% in Western Pacific, 28.5% in Latin America, 42.7% in one African country, and 9.2% in one Eastern Mediterranean country). Predominant non-PCV13 serotypes overall were 22F, 12F, 33F, 24F, 15C, 15B, 23B, 10A, and 38 (descending order), but their rank order varied by region. Conclusion Childhood IPD is associated with a wide number of serotypes. In the early years after introduction of higher valent PCVs, non-PCV13 types caused a considerable proportion of childhood IPD. Serotype data, particularly from resource-limited countries with high burden of IPD, are needed to assess the importance of serotypes in different settings. The geographic diversity of pneumococcal serotypes highlights the importance of continued surveillance to guide vaccine design and recommendations.

Burden of respiratory syncytial virus infections in China: systematic review and meta-analysis.

Background Respiratory syncytial virus (RSV) is the most important cause of acute respiratory tract infection (ARTI) related morbidity and mortality worldwide. However, the disease burden due to RSV has not been systematically summarized in China. Method A systematic search was performed in the Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and PubMed to identify available published RSV studies in China. Results A total of 489 641 patients with ARTIs from 135 studies were included in the analysis. Among patients with ARTIs, RSV accounted for 18.7% (95% confidence interval CI 17.1–20.5%). The prevalence of RSV was highest in infants (26.5%, 95% CI 23.7–29.5%) and lowest in those aged ≥16 years (2.8%, 95% CI 1.3–6.1). A higher prevalence of RSV was seen in inpatients (22%, 95% CI 19.9–24.2%) than in outpatients (14%, 95% CI 9.6–19.9%). RSV type A accounted for 63.1% (95% CI 52.3–72.8%) of all RSV infections. RSV infections occurred mainly in winter and spring. The most common clinical manifestations were cough, production of sputum, wheezing and fever. Conclusion RSV is the leading cause of viral ARTIs in China, particularly in infants and young children. Our findings are valuable for guiding the selection of appropriate therapies for ARTIs and implementation of preventive measures against RSV infections. Our data further supports the development of a successful RSV vaccine as a high priority.

Infection prevention and control of Clostridium difficile – a global review of guidelines, strategies, and recommendations

Background Clostridium difficile is the leading cause of health care–associated infections. Given the high incidence of C. difficile infection (CDI) and the lack of primary prevention through immunization, health care professionals should be aware of the most current guidance, as well as strengths and limitations of the evidence base underpinning this guidance. Methods We identified publicly available national or organizational guidelines related to CDI infection and prevention control (IPC) published between 2000 and 2015 and for any health care setting through an internet search using the Google search engine. We reviewed CDI–targeted IPC recommendations and describe the assessment of evidence in available guidelines. Results We identified documents from 28 countries/territories, mainly from acute care hospitals in North America, the Western Pacific, and Europe (18 countries). We identified only a few specific recommendations for long–term care facilities (LTCFs) and from countries in South America (Uruguay and Chile), South East Asia (Thailand), and none for Africa or Eastern Mediterranean. Of 10 IPC areas, antimicrobial stewardship was universally recognized as essential and supported by high quality evidence. Five other widely reported “strong” recommendations were: effective environment cleaning (including medical equipment), case isolation, use of personal protective equipment, surveillance, and education. Several unresolved and emerging issues were documented and currently available evidence was classified mainly as of mixed quality. Conclusion Our review underlines the need for targeted CDI IPC guidelines in several countries and for LTCFs. International harmonisation on the assessment of the evidence for best practices is needed as well as more robust evidence to support targeted recommendations.

Invasive Meningococcal Disease in Scotland, 1994 to 1999, with Emphasis on Group B Meningococcal Disease

ABSTRACT A review was carried out on 774 invasive meningococcal isolates reported to the active meningococcal surveillance system in Scotland from 1994 to 1999. This showed that serogroups B (51.7%) and C (39.2%) caused the majority of disease. The six common PorB proteins (4, 1, 15, 2B, 12, and 21) and PorA proteins (serosubtypes) (P1.4, P1.15, P1.9, P1.14, P1.7, and P1.16) accounted for 50 and 51% of all group B isolates, respectively, during the study period.

Risk factors for Clostridium difficile infections - an overview of the evidence base and challenges in data synthesis

Background Recognition of a broad spectrum of disease and development of Clostridium difficile infection (CDI) and recurrent CDI (rCDI) in populations previously considered to be at low risk has renewed attention on differences in the risk profile of patients. In the absence of primary prevention for CDI and limited treatment options, it is important to achieve a deep understanding of the multiple factors that influence the risk of developing CDI and rCDI. Methods We conducted a review of systematic reviews and meta–analyses on risk factors for CDI and rCDI published between 1990 and October 2016. Results 22 systematic reviews assessing risk factors for CDI (n = 19) and rCDI (n = 6) were included. Meta–analyses were conducted in 17 of the systematic reviews. Over 40 risk factors have been associated with CDI and rCDI and can be classified into three categories: pharmacological risk factors, host–related risk factors, and clinical characteristics or interventions. Most systematic reviews and meta–analyses have focused on antibiotic use (n = 8 for CDI, 3 for rCDI), proton pump inhibitors (n = 8 for CDI, 4 for rCDI), and histamine 2 receptor antagonists (n = 4 for CDI) and chronic kidney disease (n = 4 for rCDI). However, other risk factors have been assessed. We discuss the state of the evidence, methods, and challenges for data synthesis. Conclusion Several studies, synthesized in different systematic review, provide valuable insights into the role of different risk factors for CDI. Meta–analytic evidence of association has been reported for factors such as antibiotics, gastric acid suppressants, non–selective NSAID, and some co–morbidities. However, despite statistical significance, issues of high heterogeneity, bias and confounding remain to be addressed effectively to improve overall risk estimates. Large, prospective primary studies on risk factors for CDI with standardised case definitions and stratified analyses are required to develop more accurate and robust estimates of risk effects that can inform targeted–CDI clinical management procedures, prevention, and research.

Burden of Neisseria meningitidis infections in China: a systematic review and meta-analysis

Background Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia in children and young adults worldwide. The disease burden associated with N. meningitidis infections has not been systematically assessed in China. Therefore, we undertook this study to determine the burden of meningococcal disease in China. Method We performed a systematic review and meta–analysis of articles on N. meningitidis incidence, carriage, seroprevalence and mortality rates in China by searching the Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and PubMed for publications from January 2005 to Aug 2015. Results In total, 50 articles were included in our analysis. The overall incidence of meningococcal disease and associated mortality were estimated to be 1.84 (95% confidence interval (CI) 0.91–3.37) per 100 000 persons per year and 0.33 (95% CI 0.12–0.86) per 100 000 persons per year, respectively. N. meningitidis carriage rate among the healthy population was estimated to be 2.7% (95% CI 2.0–3.5%). Prevalence of antibodies against N. meningitidis serogroup A and C were estimated to be 77.3% (95% CI 72.4%–81.6%) and 33.5% (95% CI 27.0%–40.8%), respectively. No studies were found for serogroup specific disease burden. Conclusions The overall incidence of meningococcal disease in China is low. The lower seroprevalence of serogroup C within the population suggests that it may pose a greater risk for meningococcal disease outbreak than serogroup A. The lack of data on serogroup disease burden by age groups suggests the implementation of laboratory based meningococcal surveillance systems are urgently needed in China.

Prevalence of penicillin non-susceptible invasive pneumococcal disease in the elderly in Scotland, 1992-99

Penicillin resistance of Pneumococci is a problem in several European countries. Therefore, we examined 510 invasive pneumococcal isolates, collected between 1992 and 1999 via a national network of diagnostic laboratories covering the entire population of Scotland, for penicillin susceptibility, in order to determine the prevalence, site of infection and serogroup/type distribution of penicillin-resistant Pneumococci in the elderly (≥ 65 y). Of the 510 isolates, 91.6% (n = 467) were from blood, 4.7% (n = 24) from other sterile sites and 3.7% (n = 19) from cerebrospinal fluid. The prevalence of penicillin non-susceptible isolates during the study period was 9%. An increase in the proportion of Pneumococci non-susceptible to penicillin was detected from 1996 onwards, from 10.8% in 1996 to 14.3% in 1999. There were 2 isolates with high-level penicillin resistance, both of which were of serotype 14, accounting for 4.3% (2/46) of all non-susceptible isolates. Penicillin non-susceptible isolates belonged to the following serogroups: 14 (32.6%); 9 (30.4%); 6 (19.6%); 23 (10.9%); and 19 (6.5%). The leading non-susceptible serotype/group varied according to the specimen type: serotype 14 for blood and serogroup 9 for all other sterile sites. Current polysaccharide and new 7-, 9- and 11-valent conjugate vaccine formulations included the serogroups responsible for all the penicillin non-susceptible isolates detected. Therefore vaccination represents the most effective strategy for decreasing the burden of drug resistance. Constant surveillance of the patterns of antibiotic non-susceptible isolates, the site of infection and the serogroup/type are necessary in order to select antibiotic therapy and establish vaccination policy for the prevention of invasive pneumococcal disease.

Global etiology of bacterial meningitis: A systematic review and meta-analysis

Bacterial meningitis is a global public health concern, with several responsible etiologic agents that vary by age group and geographical area. The aim of this systematic review and meta-analysis was to assess the etiology of bacterial meningitis in different age groups across global regions. PubMed and EMBASE were systematically searched for English language studies on bacterial meningitis, limited to articles published in the last five years. The methodological quality of the studies was assessed using a customized scoring system. Meta-analyses were conducted to determine the frequency (percentages) of seven bacterial types known to cause meningitis: Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, group B Streptococcus agalactiae, Staphylococcus aureus, and Listeria monocytogenes, with results being stratified by six geographical regions as determined by the World Health Organization, and seven age groups. Of the 3227 studies retrieved, 56 were eligible for the final analysis. In all age groups, S. pneumoniae and N. meningitidis were the predominant pathogens in all regions, accounting for 25.1–41.2% and 9.1–36.2% of bacterial meningitis cases, respectively. S. pneumoniae infection was the most common cause of bacterial meningitis in the ‘all children’ group, ranging from 22.5% (Europe) to 41.1% (Africa), and in all adults ranging from 9.6% (Western Pacific) to 75.2% (Africa). E. coli and S. pneumoniae were the most common pathogens that caused bacterial meningitis in neonates in Africa (17.7% and 20.4%, respectively). N. meningitidis was the most common in children aged ±1–5 years in Europe (47.0%). Due to paucity of data, meta-analyses could not be performed in all age groups for all regions. A clear difference in the weighted frequency of bacterial meningitis cases caused by the different etiological agents was observed between age groups and between geographic regions. These findings may facilitate bacterial meningitis prevention and treatment strategies.

The relative invasive disease potential of Streptococcus pneumoniae among children after PCV introduction: A systematic review and meta-analysis

OBJECTIVES Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV). METHODS We conducted a systematic review, supplemented by unpublished data, to identify data on the frequency of pneumococcal serotypes in carriage and invasive pneumococcal disease (IPD). We estimated the invasive disease potential of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI) compared with 19A (reference serotype) by meta-analysis. We report results based on a random effects model for children aged 0-23, 24-29, and 0-59 months and by invasive clinical syndromes. RESULTS In comparison with 19A, serotypes 1, 7F, and 12F had a significantly higher invasive disease potential in children aged 0-23 and 0-59 months for all IPD and clinical syndromes (OR > 5). Several non-vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a lower invasive disease potential than 19A (OR 0.1-0.3). NVTs 8, 12F, 24F, and 33F were at the upper end of the invasiveness spectrum. CONCLUSIONS There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines.