Interaction of Vaccination and Reduction of Antibiotic Use Drives Unexpected Increase of Pneumococcal Meningitis.

Antibiotic-use policies may affect pneumococcal conjugate-vaccine effectiveness. The reported increase of pneumococcal meningitis from 2001 to 2009 in France, where a national campaign to reduce antibiotic use was implemented in parallel to the introduction of the 7-valent conjugate vaccine, provides unique data to assess these effects. We constructed a mechanistic pneumococcal transmission model and used likelihood to assess the ability of competing hypotheses to explain that increase. We find that a model integrating a fitness cost of penicillin resistance successfully explains the overall and age-stratified pattern of serotype replacement. By simulating counterfactual scenarios of public health interventions in France, we propose that this fitness cost caused a gradual and pernicious interaction between the two interventions by increasing the spread of nonvaccine, penicillin-susceptible strains. More generally, our results indicate that reductions of antibiotic use may counteract the benefits of conjugate vaccines introduced into countries with low vaccine-serotype coverages and high-resistance frequencies. Our findings highlight the key role of antibiotic use in vaccine-induced serotype replacement and suggest the need for more integrated approaches to control pneumococcal infections.

Caracterização molecular de sorotipos não-vacinais de Streptococcus pneumoniae isolados de pacientes com meningite em Salvador, antes e após a implementação da vacina conjugada PCV-10 / Molecular characterization of non-vaccine serotypes of Streptococcus pneumoniae isolates from meningitis patients in Salvador, before and after implementation of the conjugate vaccine PCV-10

O advento das vacinas pneumocócicas conjugadas veio contribuir de forma decisiva para a redução da incidência dos casos de doença invasiva por S. pneumoniae em vários países do mundo. Em contrapartida, tem-se verificado um aumento de casos decorrentes de sorotipos não vacinais, que escapam da vacina e reduzem o seu efeito a partir da expansão de clones pré-existentes com consequente substituição de sorotipos e/ou do fenômeno de troca capsular (capsular switching). No Brasil, a vacina conjugada 10-valente (PCV10) foi introduzida no calendário nacional de imunização a partir de 2010. Este estudo teve como objetivo caracterizar através de técnicas fenotípicas e moleculares os sorotipos não-vacinais (SNVT) de S.pneumoniae, isolados de pacientes com meningite nos períodos anterior (janeiro/2008 - junho/2010) e posterior (julho/2010 - dezembro/2012) à implementação da vacina pneumocócica conjugada 10-valente (PCV10), na cidade de Salvador, Bahia. Os isolados de S. pneumoniae foram identificados através de métodos microbiológicos clássicos e a determinação do tipo capsular foi realizada através da técnica de Multiplex-PCR e/ou reação de Quellung. A sensibilidade a oito antimicrobianos foi realizada através da técnica de microdiluição em caldo e a caracterização genotípica por intermédio das técnicas de PFGE e MLST...

The licensure and subsequent widespread use of pneumococcal conjugate vaccines have contributed for the reduction in the overall incidence of invasive pneumococcal disease worldwide. However, the emergence of Streptococcus pneumoniae nonvaccine serotypes (SNVT), which escape from the vaccine by the expansion of pre-existing clones following serotype replacement and/or by capsular switching is a matter of concern. In 2010, Brazil introduced the 10-valent conjugate pneumococcal vaccine (PCV10) into its routine National Immunization Program. Our aim was to characterize the phenotypic and genotypic profile of S. pneumoniae non-vacine serotypes (SNVT) isolated from patients with meningitis before (January 2008 – June 2010) and after (July 2010 – December 2012) the introduction of PCV10 in Salvador, Bahia. The pneumococcal isolates were identified by classical microbiological methods and submitted to capsular deduction by multiplex-PCR and/or Quellung reaction. The antimicrobial susceptibility was performed the broth microdilution method. The genotypic profile was assessed by PFGE and MLST...

Molecular epidemiological investigation to determine the source of a fatal case of serotype 22F pneumococcal meningitis.

A child's death due to pneumococcal meningitis after contracting the disease in an after-school programme prompted an investigation to assess nasopharyngeal (NP) carriage among her contacts. The serotype of the meningitis case isolate was determined, together with the serotypes of the NP specimens of contacts, comprising the case patient's brother, the case patient's after-school programme contacts and the brother's day-care centre (DCC) contacts. NP swabs from 155 children and 69 adults were obtained. Real-time PCR and conventional multiplex PCR (CM-PCR) assays were used to detect pneumococcal carriage and determine serotypes. Broth-enriched culture of NP specimens followed by pneumococcal isolation and Quellung-based serotyping were also performed. DNA extracts prepared from cerebrospinal fluid of the index case and from the NP strain isolated from the brother and from one attendee of the brother's DCC were subjected to genotyping. Pneumococcal carriage assessed by real-time PCR and culture was 49.6 and 36.6%, respectively (P<0.05). Twenty-three serotypes were detected using CM-PCR, with serotypes 6A/6B, 14, 19F, 6C/6D, 22F/22A, 23F and 11A/11D being the most frequent. All eight serotype 22F/22A NP specimens recovered were from children attending the brother's DCC. The meningitis case isolate and the NP carriage isolate from the patient's brother were both serotype 22F and shared the same new multilocus sequence type (ST6403) with the attendee of the brother's DCC. CM-PCR proved to be useful for assessing carriage serotype distribution in a setting of high-risk pneumococcal transmission. The causal serotype appeared to be linked to the brother of the case patient and attendees of his DCC.

Protecting the herd: the remarkable effectiveness of the bacterial meningitis polysaccharide-protein conjugate vaccines in altering transmission dynamics.

Interrupting human-to-human transmission of the agents (Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae) of bacterial meningitis by new capsular polysaccharide-protein conjugate vaccines (PPCVs) has proven to be a remarkable (and unanticipated) contributor to vaccine effectiveness. Herd immunity accounts for ∼50% of the protection by meningococcal serogroup C PPCVs, pneumococcal PPCV7, and H. influenzae b PPCVs. Nasopharyngeal carriage can be reduced ≥75% for vaccine serotypes; the decrease in carriage is correlated with disease reduction in unvaccinated individuals, and the impact of herd immunity lasts for years. Based on these data, models for using herd immunity in vaccine-based prevention strategies are underway for control of meningitis in sub-Saharan Africa. Although the immunologic basis of herd immunity and impact on microbial biology need more study, protecting the unvaccinated by altering pathogen transmission dynamics is a powerful effect of PPCVs and increasingly important in vaccine introduction, implementation, and evaluation strategies.

[Vaccination against pneumococci and influenza. How good is the evidence?]. / Impfungen gegen Pneumokokken und Influenza. Wie groß ist die Evidenz?

Diseases caused by pneumococci and influenza viruses can lead to severe complications in children, in older, chronically ill and immunosuppressed patients. In an aging population in western countries they present an important cause of morbidity and mortality. Additionally, antibiotic resistance may complicate a therapy. Consequently, the need of an effective vaccine is obvious. The 23-valent polysaccharide pneumococcal vaccine has been discussed critically. New meta-analyses do not show an efficacy in preventing invasive pneumococcal disease or death of all cause. However, a very recent study has shown a significant reduction of pneumonias and death due to pneumococcal disease in nursing-home residents. The 7-valent conjugated vaccine is more immunogenic and efficient in children and first studies demonstrate its efficacy in immunosuppressed persons. In Switzerland this latter vaccine is used in children, in Germany the 7-valent vaccine has been replaced by the 13-valent conjugated vaccine since December 2009. Influenza-vaccines are effective, while vaccines with an adjuvance seem more immunogenic, in particular in older persons. The 2010/2011 influenza vaccine has been adapted and includes the pandemic influenza H1N1 2009 strain. The influenza vaccine often does not provide protection against infection, however, it does provide good efficacy against severe complications related to influenza.

[Community-acquired bacterial meningitis in the Loire-Atlantic region: evolution of pneumococcal and meningococcal sensitivity to penicillin]. / Les méningites bactériennes communautaires en Loire-Atlantique: évolution de la sensibilité à la pénicilline des pneumocoques et méningocoques.

OBJECTIVES: An epidemiological study of community-acquired bacterial meningitis was conducted in Loire-Atlantique in subjects aged over 1 month. Risk factors and changes in pneumococcal and meningococcal susceptibility to betalactams were analyzed. PATIENTS AND METHODS: All cases of proven or presumed bacterial meningitis registered by Loire-Atlantic bacteriology laboratories between May 1995 and April 1998 were analyzed. RESULTS: One hundred two cases were registered (annual incidence: 3.12 cases per 100,000 inhabitants). In children (33 cases) the main germs were meningococci (51%), pneumococci (24%) and Haemophilus influenzae (6%). In adults (69 cases), pneumococci (49%), meningococci (14%) and Listeria (4%) predominated. An underlying disease was noted 44% of the cases. Mortality was 17.6%. Sequellae were observed in 9.5%. Some degree of penicillin resistance was observed in 45% of the pneumococcal strains and in 50% of the meningococcal strains. Half of the pneumococcal strains were also resistant to third generation cephalosporins (C3G). No risk factor was significantly related to resistant strains. Susceptibility to antibiotics was not correlated with mortality for either pneumococcal or meningococcal strains, but sequellae were more frequent after meningitis caused by resistant pneumococci. CONCLUSION: For cases of community-acquired meningococcal meningitis diagnosed in 1999, it would be advisable to prescribe a combination C3G-vancomycin regimen as the first line empirical treatment while waiting for results of susceptibility tests. Certain guidelines proposed by the February 1996 consensus conference on community-acquired purulent meningitis would thus need to be amended.

[Pneumococcal meningitis resistant to penicillin and nosocomial transmission in pediatric hospitals confirmed by genomic analysis]. / Méningite à la pneumocoque résistant à la pénicilline et transmission nosocomiale en milieu hospitalier pédiatrique confirmée par analyse génomique.

BACKGROUND: Careful epidemiological studies and sophisticated diagnostic procedures are necessary to prove that bacterial infection is nosocomial in origin. DNA finger printing method can be useful with this aim in view. CASE REPORTS: A 11 month-old girl suffered from a febrile pneumonia. She developed acute meningitis 15 days later; culture of CSF grew Streptococcus pneumoniae, serotype 23 F, resistant to beta-lactamines, erythromycin and cotrimoxazole. She died 24 hours later. Five days after this death, a 5 month-old infant hospitalized in the next bed developed an acute pulmonary infection due to the same strain with the same bacterial characteristics; this patient was cured with cefotaxime plus vancomycin and gentamicin. Randomly amplified polymorphic DNA analysis showed an identical profile of both strains. CONCLUSION: This is the first case of meningitis due to penicillin-resistant Streptococcus pneumoniae (PRSP) associated with nosocomial spread between two children in adjacent beds. This case suggests that it is necessary to isolate patients with PRSP infection during hospitalization.

Streptococcus pneumoniae invasive disease in the neonatal period: an increasing problem?

UNLABELLED: A series of 11 cases of invasive infection with Streptococcus pneumoniae, occurring over an 11-year period, is reported. Eight of the 11 cases occurred during the final 2 years of the study suggesting that the incidence of infection may be increasing. Infection carries a high mortality (3/11). Morbidity includes meningitis, convulsions and respiratory failure. In one case S. pneumoniae meningitis occurred in both mother and newborn. Most mothers who carried the organism were asymptomatic at the time of delivery. CONCLUSION: S. pneumoniae should be specifically sought in swabs taken from the pregnant mother and newborn and if isolated, even in the absence of symptoms, antibiotic therapy against the organism should be strongly considered.

[The epidemiology of neonatal meningitis]. / Epidemiologiia neonatal'nykh meningitov.

The epidemiological features of meningitides in newborns have been studied and criteria making it possible to distinguish the cases of intrauterine and postnatal infection have been proposed. The overwhelming majority of these infections has been found to occur due to hospital infections caused by enterobacteria and nonfermenting bacteria. In meningitides of this etiology the sources of infection are newborns colonized by these microorganisms. Infection is transmitted through everyday contacts through the hands of the medical staff. Besides, moist environmental objects serve as the additional reservoir of infection.