Emergence of the M phenotype of erythromycin-resistant pneumococci in South Africa.

Erythromycin-resistant pneumococci have been isolated in South Africa since 1978; however, from 1987 to 1996, resistance to macrolides was only detected in 270 (2.7%) of 9,868 blood or cerebrospinal fluid (CSF) pneumococcal isolates, most of which were obtained from the public sector. In South Africa, macrolide use in the public sector is estimated at 56% of that in the private sector. Most erythromycin-resistant strains (89%) exhibited resistance to erythromycin and clindamycin (macrolide-lincosamide-streptogramin B phenotype). In the United States, most erythromycin-resistant pneumococci exhibit the newly described M phenotype (resistance to erythromycin alone), associated with the mefE gene. The M phenotype in South Africa increased significantly in the last 10 years, from 1 of 5,115 to 28 of 4,735 of blood and CSF isolates received from 1987 to 1991 compared with 1992 to 1996 (p = 5 x 10(-7)). These data suggest that, although macrolide resistance in pneumococci remains low in the public sector, the mefE gene is rapidly emerging in South Africa

Novel Approaches to the Identification of Streptococcus pneumoniae as the Cause of Community-Acquired Pneumonia

Current diagnostic tests lack sensitivity for the identification of the bacterial etiology of pneumonia. Attempts during the past 2 decades to improve sensitivity of detection of bacterial constituents in blood by use of antibody-antigen complexes and polymerase chain reaction have been disappointing. Recent data using pneumococcal conjugate vaccines as probes suggest that increased levels of both C-reactive protein and procalcitonin may be useful adjuncts to chest radiographs in the selection of patients with presumed bacterial pneumonia for inclusion in clinical trials. Among pneumococcal diagnostics currently under investigation, quantitative real-time polymerase chain reaction of respiratory secretions, as well as urinary antigen detection and pneumococcal surface adhesin A serological analysis for adults, are candidates for use in future clinical trials of antibiotic

Use of Procalcitonin and C-Reactive Protein to Evaluate Vaccine Efficacy against Pneumonia

BACKGROUND: Pneumonia remains the leading cause of death in young children. The poor specificity of chest radiographs (CXRs) to diagnose pneumococcal pneumonia may underestimate the efficacy of pneumococcal conjugate vaccine in preventing pneumococcal pneumonia. METHODS AND FINDINGS: The efficacy of nine-valent pneumococcal conjugate vaccine among children not infected with HIV (21%; 95% confidence interval, 1%–37%) increased when CXR-confirmed pneumonia was associated with serum C-reactive protein of 120 mg/l (12mg/dl) or more and procalcitonin of 5.0 ng/ml or more (64%; 95% confidence interval, 23%–83%). Similar results were observed in children infected with HIV. CONCLUSION: C-reactive protein and procalcitonin improve the specificity of CXR to diagnose pneumococcal pneumonia and may be useful for the future evaluation of the effectiveness of pneumococcal conjugate vaccine in preventing pneumococcal pneumonia

Interrelationship of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus colonization within and between pneumococcal-vaccine naïve mother-child dyads

Background: A high prevalence of bacterial nasopharyngeal co-infections has been reported in children, however, such data is limited in adults. We examined the interaction of Haemophilus influenzae, Staphylococcus aureus and Streptococcus pneumoniae pharyngeal colonization in mother-child dyads. Methods: Pneumococcal-vaccine naïve children and their mothers had pharyngeal swabs undertaken at 1.6, 2.5, 3.5, 4.5, 7.4, 9.5, 12.5, 16.2 and 24.2 months of child’s age. Swabs were cultured for S. pneumoniae, H. influenzae and S. aureus using standard microbiologic methods. Multivariate generalized estimating equation-models were used to explore the associations of the three bacteria within and between children and their mothers. Results: In children, the observed probability of co-colonization was higher than expected. Well-defined associations in colonization between the bacteria were observed in children but not among mothers. In children, a synergistic association was observed between S. pneumoniae and H. influenzae (Adjusted odds ratio (AOR): 1.75, 95% CI: 1.32-2.32) and a negative association between S. pneumoniae and S. aureus (AOR: 0.51, 95% CI: 0.39-0.67) or H. influenzae and S. aureus (AOR: 0.24, 95% CI: 0.16-0.34) colonization. Additionally, all three bacteria had a higher likelihood of concurrent colonization. There was a strong association in colonization by the bacteria in children and their mothers, including increased likelihood of maternal colonization if the child was colonized by S. pneumoniae (AOR: 1.84, 95% CI: 1.28-2.63) and H. influenzae (AOR: 6.34, 95% CI: 2.24-18.0). Conclusions: The effects of immunization of children with pneumococcal-conjugate-vaccine in settings such as ours needs monitoring with regard to potential changes of pharyngeal bacterial ecology which could occur in vaccinated and –unvaccinated age-groups

The case for launch of an international DNA-based birth cohort study

The global health agenda beyond 2015 will inevitably need to broaden its focus from mortality reduction to the social determinants of deaths, growing inequities among children and mothers, and ensuring the sustainability of the progress made against the infectious diseases. New research tools, including technologies that enable high-throughput genetic and ‘-omics’ research, could be deployed for better understanding of the aetiology of maternal and child health problems. The research needed to address those challenges will require conceptually different studies than those used in the past. It should be guided by stringent ethical frameworks related to the emerging collections of biological specimens and other health related information. We will aim to establish an international birth cohort which should assist low- and middle-income countries to use emerging genomic research technologies to address the main problems in maternal and child health, which are still major contributors to the burden of disease globally

The Battle against Emerging Antibiotic Resistance: Should Fluoroquinolones Be Used to Treat Children?

Inappropriate use of antibiotic drugs in humans and animals has led to widespread resistance among microbial pathogens. Resistance is the phenotypic expression corresponding to genetic changes caused by either mutation or acquisition of new genetic information. In some cases, multidrug resistance occurs. Streptococcus pneumoniae is one of the most important respiratory pathogens, playing a major role in both upper and lower respiratory tract infections. Pneumococcal resistance to antimicrobials may be acquired by means of horizontal transfer followed by homologous recombination of genetic material from the normal flora of the human oral cavity or by means of mutation. Resistance to penicillins and macrolides has been increasing for some time, but, recently, fluoroquinolone resistance has become an issue as well. We are concerned that, if fluoroquinolones are approved for use in children, their widespread use will result in rapid emergence of pneumococcal resistance, because children are more often colonized in the nasopharynx with high-density populations of pneumococci than are adult

Imputing direct and indirect vaccine effectiveness of childhood pneumococcal conjugate vaccine against invasive disease by surveying temporal changes in nasopharyngeal pneumococcal colonization

The limited capabilities in most low-middle income countries to study the benefit of pneumococcal conjugate vaccine (PCV) against invasive pneumococcal disease (IPD), calls for alternate strategies to assess this. We used a mathematical model, to predict the direct and indirect effectiveness of PCV by analyzing serotype specific colonization prevalence and IPD incidence prior to and following childhood PCV immunization in South Africa. We analyzed IPD incidence from 2005-2012 and colonization studies undertaken in HIV-uninfected and HIV-infected child-mother dyads from 2007-2009 (pre-PCV era), in 2010 (7-valent PCV era) and 2012 (13-valent PCV era). We compared the model-predicted to observed changes in IPD incidence, stratified by HIV-status in children >3 months to 5 years and also in women aged >18-45 years. We observed reductions in vaccine-serotype colonization and IPD due to vaccine serotypes among children and women after PCV introduction. Using the changes in vaccine-serotype colonization data, the model-predicted changes in vaccine-serotype IPD incidence rates were similar to the observed changes in PCV-unvaccinated children and adults, but not among children <24 months. Surveillance of colonization prior and following PCV use can be used to impute PCVs' indirect associations in unvaccinated age groups, including in high HIV-prevalence settings

Extended Generalised Pareto Models for Tail Estimation

The most popular approach in extreme value statistics is the modelling of threshold exceedances using the asymptotically motivated generalised Pareto distribution. This approach involves the selection of a high threshold above which the model fits the data well. Sometimes, few observations of a measurement process might be recorded in applications and so selecting a high quantile of the sample as the threshold leads to almost no exceedances. In this paper we propose extensions of the generalised Pareto distribution that incorporate an additional shape parameter while keeping the tail behaviour unaffected. The inclusion of this parameter offers additional structure for the main body of the distribution, improves the stability of the modified scale, tail index and return level estimates to threshold choice and allows a lower threshold to be selected. We illustrate the benefits of the proposed models with a simulation study and two case studies.Comment: 18 pages, 7 figure