Spatial analysis of pneumococcal meningitis in São Paulo in the pre- and post-immunization era

ABSTRACT OBJECTIVE To analyze the pneumococcal meningitis incidence rates in the State of São Paulo, Brazil, by age group, municipalities and micro-regions, as well as the spatial distribution of pneumococcal meningitis incidence rates among children under 5 years old in the pre- (2005-2009) and post-vaccination (2011-2013) periods and its associations with socioeconomic variables and vaccination coverage. METHODS The data source was the Brazilian Notifiable Diseases Information System. For the pre- and post-vaccination periods, thematic maps were built for pneumococcal meningitis incidence in under-5 children, by São Paulo state micro-regions, vaccination coverage and socioeconomic variables, using QGIS 2.6.1 software. Scan statistics performed by the SatScan 9.2 software were used to analyze spatial and spatiotemporal clusters in São Paulo municipalities and micro-regions. A Bayesian inference for latent Gaussian model with zero-inflated Poisson model through the integrated nested Laplace approximation was used in the spatial analysis to evaluate associations between pneumococcal meningitis incidence rates and socioeconomic variables of interest in São Paulo micro-regions. RESULTS From 2005 to 2013, 3,963 pneumococcal meningitis cases were reported in São Paulo. Under-5 children were the most affected in the whole period. In the post-vaccination period, pneumococcal meningitis incidence rates decreased among this population, particularly among infants (from 4.17/100,000 in 2005 to 2.54/100,000 in 2013). Two clusters were found in pre-vaccination - one of low risk for pneumococcal meningitis, in the northwest of the state (OR = 0.45, p = 0.0003); and another of high risk in the southeast (OR = 1.62, p = 0.0000). In the post-vaccination period, only a high-risk cluster remained, in the southeast (RR = 1.97, p = 0.0570). In Bayesian analysis, wealth was the only variable positively associated to pneumococcal meningitis (RR = 1.026, 95%CI 1.002-1.052). CONCLUSIONS Pneumococcal meningitis is probably underdiagnosed and underreported in São Paulo. Differentiated rates of pneumococcal meningitis diagnosis and reporting in each microregion, according to the São Paulo Index of Social Responsibility, might explain our results.

Increased Risk of Late-onset Streptococcus pneumoniae Meningitis in Adults With Prior Head or Spine Surgeries.

In a case-control study within the Kaiser Permanente Northern California adult population, prior head or spine surgery was associated with increased Streptococcus pneumoniae meningitis outside of the postoperative period (no prior head or spine surgery; odds ratio, 6.0 [95% confidence interval, 1.9-18.6]). Among the cases, only 33.3% had received any prior pneumococcal vaccinations.

Pneumococcal Meningitis in Adults after Introduction of PCV7 and PCV13, Israel, July 2009-June 20151.

The indirect effect of pneumococcal conjugate vaccine on adult pneumococcal meningitis has not been thoroughly investigated. We present data from active surveillance on pneumococcal meningitis in adults in Israel occurring during July 2009-June 2015. Pneumococcal meningitis was diagnosed for 221 patients, 9.4% of all invasive pneumococcal disease (IPD) cases. Although overall IPD incidence decreased during the study period, meningitis increased nonsignificantly from 0.66 to 0.85 cases/100,000 population. Incidence of vaccine type (VT) pneumococcal meningitis (VT13) decreased by 70%, but non-VT13 pneumococcal meningitis increased from 0.32 to 0.75 cases/100,000 population (incident rate ratio 2.35, 95% CI 1.27-4.35). Pneumococcal meningitis patients were younger and healthier than nonmeningitis IPD patients, and 20.2% had a history of previous head surgery or cerebrospinal fluid leak compared with <2.0% of nonmeningitis patients (p<0.0001). Non-VT13 types that rarely cause IPD (15B/C, 6C, 23A, 23B, 24F) seem to be emerging as common causes of meningitis.

Meningitis neumocócica en Cantabria (España) en la era de las vacunas conjugadas antineumocócicas (2001-2015) / Pneumococcal meningitis in Cantabria (Spain) in the pneumococcal conjugate vaccine era (2001-2015)

Objetivo. Analizar las características de la meningitis neumocócica en < 14 años tras la comercialización de vacunas antineumocócicas conjugadas en nuestra comunidad. Métodos. Estudio retrospectivo de los casos de meningitis neumocócica en el que se analizaron dos períodos: pre vacuna antineumocócica trecevalente (VNC13v) (2001-2010) y post-VNC13v (2010-2015). Se recogieron datos demográficos y clínicos de los pacientes y datos microbiológicos. Resultados. Se diagnosticaron 18 casos. La incidencia media pre-VNC13v fue de 2,3/100 000, y disminuyó a 0,5/100 000 tras la VNC13v. Los serotipos más frecuentemente identificados fueron 6A y 10A (pre-VNC13v); 6B y 15B (post-VNC13v, solo dos casos). Trece de dieciocho pacientes ingresaron en la Unidad de Cuidados Intensivos. Todos los casos fueron tratados con cefotaxima y recibieron dexametasona 14/18. Seis pacientes sobrevivieron con secuelas y uno falleció. Conclusión. Se observa un importante descenso en la incidencia de meningitis neumocócica desde la comercialización de la VNC13v, por lo que cabe esperar que tras su introducción sistemática se produzca un descenso aún mayor.

Objective. To analyze the characteristics of pneumococcal meningitis in children < 14 years old following the market introduction of pneumococcal conjugate vaccines in our community. Methods. Retrospective study of pneumococcal meningitis cases with a two-period analysis: pre-13-valent pneumococcal conjugate vaccine (PCV13) (2001-2010) and post-PCV13 (2010-2015). Patient demographic and clinical data, and microbiological data were collected. Results. Eighteen cases were diagnosed. The mean incidence in the pre-PCV13 period was 2.3/100 000, which reduced to 0.5/100 000 after the PCV13 introduction. The most commonly identified serotypes were 6A and 10A (pre-PCV13); 6B and 15B (post-PCV13, only 2 cases). Out of 18 patients, 13 were admitted to the intensive care unit. All cases were treated with cefotaxime, and 14/18 received dexamethasone. Six patients survived with sequelae, and 1 died. Conclusion. A major reduction has been observed in the incidence of pneumococcal meningitis since the introduction of the PCV13 to the market, so an even greater reduction is expected following its systematic introduction.

Determination of Characteristics of Erythromycin Resistant Streptococcus pneumoniae with Preferred PCV Usage in Iran.

Amongst 100 Streptococcus pneumoniae isolated from clinical cases and nasopharynx of healthy individuals, 60 erythromycin resistant strains were isolated and characterized using MLST, PFGE, transposon analysis and Quellung reaction. Most of the S. pneumoniae erythromycin resistant (80%) were found to be attributable to the ermB-edncoded ribosome methylase activity which differs from the dominant mechanism of macrolide resistance seen in North America. The most predominant transposons were; Tn1545/6003 (27%), Tn6002 (22%), Tn2009 (20%), Tn2010 (17%). Number of the clinical isolates carrying Tn2010 was more significant than the normal flora. The serotypes found were; 14 (33%), 3 (22%), 23F (15%), 19F (15%), 19A (7%), 6A (3%), 9V (3%) and 6B (2%). The most prevalent serotypes among the clinical (n = 28) and normal flora (n = 32) isolates were serotypes 14 (46%) and 3 (31%), respectively. The most prevalent vaccine serotypes amongst the clinical isolates and the healthy individuals were pneumococcal conjugate vaccines (PCV) 13 and PCV10, respectively. PFGE revealed 34 pulsotypes with 9 common and 25 single types. Significant number of the normal isolates belonged to CT5 and CT6. On the other hand, significant number of clinical isolates belonged to CT8 as compared to the normal flora isolates. MLST showed 2 dominant sequence types. ST3130 (23%) and ST180 (22%) were the most predominant sequence types in the clinical and normal isolates, respectively. There was no significant difference in other sequence types between clinical and normal flora isolates. Three polyclonal complexes including Sweden15A -25, Spain23F-1 and Spain9V-3 constituted 58% of the isolates. Our results suggest that the genetic diversity and transposon distribution were high among S. pneumoniae, particularly in the isolates containing erm(B) and double antibiotic resistant genes (erm/mef). The results presented here could influence the change in the current vaccination practices in Iran which currently calls for vaccination with PCV7 or PCV10.

Cigarette Smoke Attenuates the Nasal Host Response to Streptococcus pneumoniae and Predisposes to Invasive Pneumococcal Disease in Mice.

Streptococcus pneumoniae is a leading cause of invasive bacterial infections, with nasal colonization an important first step in disease. While cigarette smoking is a strong risk factor for invasive pneumococcal disease, the underlying mechanisms remain unknown. This is partly due to a lack of clinically relevant animal models investigating nasal pneumococcal colonization in the context of cigarette smoke exposure. We present a model of nasal pneumococcal colonization in cigarette smoke-exposed mice and document, for the first time, that cigarette smoke predisposes to invasive pneumococcal infection and mortality in an animal model. Cigarette smoke increased the risk of bacteremia and meningitis without prior lung infection. Mechanistically, deficiency in interleukin 1α (IL-1α) or platelet-activating factor receptor (PAFR), an important host receptor thought to bind and facilitate pneumococcal invasiveness, did not rescue cigarette smoke-exposed mice from invasive pneumococcal disease. Importantly, we observed cigarette smoke to attenuate nasal inflammatory mediator expression, particularly that of neutrophil-recruiting chemokines, normally elicited by pneumococcal colonization. Smoking cessation during nasal pneumococcal colonization rescued nasal neutrophil recruitment and prevented invasive disease in mice. We propose that cigarette smoke predisposes to invasive pneumococcal disease by suppressing inflammatory processes of the upper respiratory tract. Given that smoking prevalence remains high worldwide, these findings are relevant to the continued efforts to reduce the invasive pneumococcal disease burden.

Clinical and bacteriological characteristics of invasive pneumococcal disease after pneumococcal 10-valent conjugate vaccine implementation in Salvador, Brazil

Abstract Invasive pneumococcal disease is a relevant public health problem in Brazil, especially among children and the elderly. In July/2010 a 10-valent pneumococcal conjugate vaccine was introduced to the immunization schedule of Brazilian children under two years of age. Between July/2010 and December/2013 we conducted a case-series study on invasive pneumococcal disease in Salvador, Brazil to describe the clinical and bacteriological profile of invasive pneumococcal disease cases during the post-implementation period. Eighty-two cases were eligible. Mean age was 31 years (interquartile range, 3–42); 17.1% and 30.5% were under 2 years and 5 years, respectively. Pneumococcal meningitis (n = 64, 78.1%), bacteraemic pneumococcal pneumonia (n = 12, 14.6%) and bacteraemia (n = 6, 7.3%) were the clinical syndromes identified. Thirty-three different serotypes were found. Of these, serotype 14 (n = 12, 14.6%) was the most common, followed by 23F (n = 10, 12.2%), 12F (n = 8, 9.8%), 18 C (n = 5, 6.1%) and 6B (n = 5, 6.1%). Investigations conducted in Salvador in the pre-vaccine period did not identify serotype 12F as one of the most prevalent serotypes. Increase of serotype 12F was observed in different regions of Brazil, in the post-vaccine period. Among children under two years of age, the target group for 10-valent pneumococcal conjugate vaccine, 11 (78.6%) of the 14 isolated strains of Streptococcus pneumoniae belonged to vaccine serotypes; at least 50% of these children were not vaccinated. The relatively recent implementation of 10-valent pneumococcal conjugate vaccine in Brazil reinforces the need to maintain an active surveillance of invasive pneumococcal disease cases, considering the possible increase of invasive pneumococcal disease cases related to non-vaccine serotypes and the changes on the clinical presentation of the disease.

Invasive Bacterial Infection in Patients with Interleukin-1 Receptor-associated Kinase 4 Deficiency: Case Report.

Interleukin-1 receptor-associated kinase 4 (IRAK4) deficiency (OMIM #607676) is a rare primary immunodeficiency of innate immune defect. We identified 10 patients from 6 families with IRAK4 deficiency in Japan, and analyzed the clinical characteristics of this disease. Nine patients had homozygous c.123_124insA mutation, and 1 patient had c.123_124insA and another nonsense mutation (547C>T). Umbilical cord separation occurred on the 14th day after birth or thereafter. Two patients had no severe infections owing to the prophylactic antibiotic treatment. Severe invasive bacterial infections occurred before the age of 3 in the other 8 patients. Among them, 7 patients had pneumococcal meningitis. Five patients died of invasive bacterial infection during infancy, although intravenous antibiotic treatment was started within 24 hours after onset in 4 patients among them. Analysis of cerebrospinal fluid of the patients who had fatal meningitis revealed very low glucose levels with only mild pleocytosis. The clinical courses of invasive bacterial infections were often rapidly progressive despite the early, appropriate antibiotic treatment in IRAK4 deficiency patients. The early diagnosis and appropriate prophylaxis of invasive bacterial infections are necessary for the patients.

Impact of 10-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children up to two years of age in Brazil / Impacto de la vacuna neumocócica conjugada 10-valente en la meningitis neumocócica en niños de hasta dos años de edad en Brasil / Impacto da vacina pneumocócica conjugada 10-valente na meningite pneumocócica em crianças com até dois anos de idade no Brasil

The objective of this study was to analyze the impact of vaccination against Streptococcus pneumoniae on the morbidity and mortality from pneumococcal meningitis in children ≤ 2 years in Brazil, from 2007 to 2012. This is a descriptive study and ecological analysis using data from the Information System on Notifiable Diseases. Pre-vaccination (2007-2009) and post-vaccination (2011-2012) periods were defined to compare incidence rates and mortality. A total of 1,311 cases and 430 deaths were reported during the study period. Incidence decreased from 3.70/100,000 in 2007 to 1.84/100,000 in 2012, and mortality decreased from 1.30/100,000 to 0.40/100,000, or 50% and 69% respectively, with the greatest impact in the 6-11 month age group. This decrease in Pneumococcal meningitis morbidity and mortality rates two years after introduction of the 10-valent pneumococcal conjugate vaccine suggests its effectiveness.

El objetivo de este estudio fue analizar el impacto de la vacunación contra el Streptococcus pneumoniae en la morbilidad y mortalidad de la meningitis neumocócica en niños ≤ 2 años en Brasil, 2007-2012. Se trata de un estudio descriptivo ecológico que analiza los datos del Sistema de Información Enfermedades de Notificación Obligatoria en Brasil. El período previo (2007-2009) y posterior a la vacunación (2011-2012) fueron examinados para comparar las tasas de incidencia y mortalidad. 1.311 casos de meningitis neumocócica con 430 muertes se registraron durante el período de estudio. Hubo una disminución de la incidencia de 3,70 casos por 100.000 habitantes en 2007, a 1,84/100.000 en 2012, mientras que la tasa de mortalidad cayó 1,30 a 0,40 óbitos/100.000, se produjeron reducciones del 50% y 69%, respectivamente, con mayores impactos identificados entre los niños de 6-11 meses de edad. Los resultados indican una reducción en la morbilidad y mortalidad por meningitis neumocócica dos años después de la introducción de la vacuna conjugada antineumocócica 10-valente, lo que sugiere su eficacia.

O objetivo deste trabalho foi analisar o impacto da vacinação contra o Streptococcus pneumoniae na morbidade e mortalidade por meningite pneumocócica em crianças ≤ 2 anos, no Brasil, entre 2007-2012. Este é um estudo descritivo com análise ecológica, utilizando dados do Sistema de Informação de Agravos de Notificação. Foram definidos os períodos pré-vacinal (2007-2009) e pós-vacinal (2011-2012) para comparar as taxas de incidência e mortalidade. Foram identificados 1.311 casos e 430 óbitos no período do estudo. A taxa de incidência diminuiu de 3,70/100.000 no ano de 2007 para 1,84/100.000 em 2012, e a mortalidade reduziu de 1,30/100.000 para 0,40/100.000, o que significa uma redução de 50% e 69%, respectivamente, com maior impacto identificado na faixa etária de 6 a 11 meses. Os resultados indicam uma diminuição nos indicadores de morbidade e mortalidade de meningite pneumocócica, observados dois anos após a introdução da vacina pneumocócica conjugada 10-valente, sugerindo sua efetividade.

Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types.

Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored. Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes. Invasive disease potential for pneumococcal serotypes were calculated using 165 invasive and 550 carriage isolates from children. The invasive disease potential was lower for non-PCV13 compared to vaccine-type strains. Patients infected with non-PCV13 strains had more underlying diseases, were less likely to have pneumonia and, in adults, tended to have a higher mortality. Furthermore, patients infected with pneumococci belonging to clonal serotypes only expressing non-PCV13 capsules had a higher risk for septicaemia and mortality. PCV vaccination will probably lead to a decrease in invasive pneumococcal disease but an alteration in the clinical manifestation of invasive pneumococcal disease. Genetic lineages causing invasive pneumococcal disease in adults often express non-vaccine serotypes, which can expand after vaccination with an increased risk of infection in patients with underlying diseases.

Vaccination recommendations and risk of meningitis following cochlear implantation.

PURPOSE OF REVIEW: The Centers for Disease Control and Prevention has established vaccination guidelines for cochlear implant recipients to address the concern for implant-associated bacterial meningitis. Since their inception in 2002, these guidelines have undergone several revisions. We review the rationale and development of the current vaccination schedule. RECENT FINDINGS: Bacterial meningitis is a rare yet potentially life-threatening complication of cochlear implantation. The recommendations for pneumococcal vaccination have evolved to a state in which nearly all cochlear implant patients receive a combination of both the PCV7 or PCV13 and PPSV23. SUMMARY: Streptococcus pneumoniae vaccinations have dramatically decreased the incidence of serotype-specific invasive pneumococcal disease across all age groups. However, the optimal timing of immunization remains unclear in cochlear implant candidates.

Meningitis neumocócica: experiencia de 12 años en un hospital pediátrico, previa a la inmunización universal con vacuna conjugada / Pneumococcal meningitis: A 12 year experience in a children's hospital prior to the universal immunization with a conjugate vaccine

Introducción. La meningitis por Streptococcus pneumoniae provoca frecuentemente elevada morbimortalidad. El objetivo del presente estudio fue identificar las características epidemiológicas y clínicas, la susceptibilidad antibiótica y la evolución de los niños con meningitis por neumococo antes de la introducción de la vacuna en Argentina. Métodos. Se incluyeron pacientes menores de 18 años internados en el Hospital J. P. Garrahan entre 1999 y 2010. Se revisaron los registros del laboratorio de microbiología y las historias clínicas de los niños. Resultados. Se identificaron 111 niños con meningitis por S. pneumoniae. En el período 1999-2002, hubo 40 casos, 35 en 2003-2006 y 36 en 2007-2010. La media de edad fue 7 meses (r: 1-191). Eran inmunocompetentes 104 pacientes (94%). Solo 20 pacientes (18%) tenían enfermedad de base. La presentación clínica más frecuente fue el compromiso neurológico en 80 pacientes (75%) y la sepsis en 59 pacientes (53%). Requirieron admisión en terapia intensiva 49 pacientes (44%). Otro foco clínico de infección estuvo presente en 24 pacientes (22%); en la mitad de ellos, neumonía. El cultivo de líquido cefalorraquídeo fue positivo en 103 pacientes (93%) y los hemocultivos en 88 pacientes (79%). Se identificó resistencia a la penicilina en 15% de los casos y en el 5% resistencia a cefotaxima. La resistencia antibiótica disminuyó a lo largo de los años. Presentaron complicaciones 56 pacientes (50%), y 11 pacientes (10%) fallecieron por la infección. Conclusión. La resistencia de S. pneumoniae a los antimicrobianos disminuyó a lo largo de los años. Es importante mantener la vigilancia epidemiológica para evaluar el impacto de la vacunación en Argentina

Introduction. Pneumococcal meningitis is caused by Streptococcus pneumoniae and has high morbidity and mortality rates. The objective of this study was to identify the epidemiological and clinical characteristics, antibiotic sensitivity and evolution of pneumococcal meningitis in children prior to the introduction of the vaccine in Argentina. Methods. Patients younger than 18 years old hospitalized at Hospital J. P. Garrahan between 1999 and 2010 were included. Children's microbiology lab records and case records were reviewed. Results. One hundred and eleven children with S. pneumoniae meningitis were identified. Forty cases were found in the 1999-2002 period, 35 in the 2003-2006 period, and 36 in the 2007- 2010 period. The mean age was 7 months old (range: 1-191). One hundred and four patients were immunocompetent (94%). Only 20 patients (18%) had an underlying disease. The most commonly observed clinical presentation was neurological involvement in 80 patients (75%), and sepsis in 59 (53%). Forty-nine patients (44%) had to be admitted to the ICU. A second clinical source of infection was identified in 24 patients (22%); half of these cases corresponded to pneumonia. Positive findings were observed in the cerebrospinal fluid culture of 103 patients (93%) and in the blood culture of 88 (79%). Resistance to penicillin was identified in 15% of cases, while 5% showed resistance to cefotaxime. Antibiotic resistance was reduced over the years. Complications occurred in 56 patients (50%), and 11 (10%) died because of the infection. Conclusion. Antimicrobial resistance by S. pneumoniae was reduced over time. It is important to maintain epidemiological surveillance to assess the impact of immunization in Argentina.

Meningitis neumocócica en niños menores de 15 años: Dieciséis años de vigilancia epidemiológica en Misiones, Argentina / Pneumococcal meningitis in children under 15 years of age in Misiones (Argentina): Sixteen year's epidemiological surveillance

Se presentan en este trabajo los resultados de 16 años de vigilancia epidemiológica de meningitis neumocócica llevada a cabo en el Hospital Provincial de Pediatría de Misiones (Argentina), antes de la introducción de la vacuna conjugada al calendario nacional. En el período que va de enero de 1994 a diciembre de 2009 se diagnosticaron 167 casos de meningitis por Streptococcus pneumoniae en niños (1 mes-15 años). La tasa de ataque cada 100 000 niños varió entre 19,2 (1997) y 4,3 (2009), con una media de 10,6 y una tendencia en disminución (y = ""0,689x + 16,52). Esto fue a expensas del grupo de niños entre 1 y 11 meses (94/167, 56 %), en el que disminuyó de 146,6 a 34,8 casos cada 100 000 niños. El 30,7 % de los aislamientos (46/150) fueron resistentes a penicilina y el 16,7 % (25/150) no sensibles a cefotaxima. La resistencia a β-lactámicos se incrementó a partir de 1997 y comenzó a disminuir en 2005. Se detectaron 19 serotipos, predominó el 14 (32 %; 40/125). El 84,8 % de los aislamientos quedaron circunscriptos a nueve serotipos: 14, 5, 1, 7F, 18C, 6B, 9N, 9V y 4. La cobertura teórica en los niños < 2 años y > 2 años fue de 84,1 % (74/88) y 83,8 % (31/37) con la vacuna 10-valente, y de 89,8 % (79/88) y 83,8 % (31/37) con la vacuna 13-valente, respectivamente. La resistencia a penicilina estuvo circunscripta a 8 serotipos (14, 6B, 6A, 9V, 4, 23B, 1 y 19A), y la no sensibilidad a cefotaxima a 3 serotipos (14, 9V y 1), el más importante fue en ambos casos el serotipo 14. Este estudio permitirá evaluar el impacto de la implementación de las vacunas conjugadas en nuestra zona.

We report the results of pneumococcal meningitis surveillance conducted at the Provincial Pediatric Hospital of Posadas, Misiones (Argentina), before the conjugate vaccine was introduced into the national vaccination schedule. Between January 1994 and December 2009, 167 cases of Streptococcus pneumoniae meningitis were diagnosed in children aged 1 month to 15 years. The attack rate/100,000 children ranged from 19.2 (1997) to 4.3 (2009), with a mean of 10.6 and a tendency to decrease (y=""0.689x+16.52). The number of cases per 100,000 children decreased from 146.6 to 34.8 and particularly involved the group of children aged 1 to 11 months (94/167, 56%). Thirty point seven percent (30.7%) (46/150) of the isolates were resistant to penicillin whereas 16.7% (25/150) were non-susceptible to cefotaxime. β-lactam resistance increased as from 1997 and began to decline in 2005. Nineteen serotypes were detected; type 14 was predominant and accounted for 32% (40/125). Eighty four point eight percent (84.8%) of the isolates were circumscribed to nine serotypes: 14, 5, 1, 7F, 18C, 6B, 9N, 9V and 4. Theoretical coverage for patients aged <2 years and >2 years was 84.1% (74/88) and 83.8% (31/37) for the 10-valent vaccine and 89.8 % (79/88) and 83.8% (31/37) for the 13-valent vaccine respectively. Penicillin resistance was restricted to 8 serotypes (14, 6B, 6A, 9V, 4, 23B, 19A1) and nonsusceptibility to cefotaxime was circumscribed to 3 serotypes (14, 9V and 1). This study will allow to evaluate the impact of the implementation of conjugate vaccines on our area.

Cost-effectiveness of new adult pneumococcal vaccination strategies in Italy.

Community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) are very relevant pathologies among elderly people (≥ 65 y old), with a consequent high disease burden. Immunization with the 23-valent pneumococcal polysaccharide vaccine (PPV23) has been differently implemented in the Italian regions in the past years, reaching overall low coverage rates even in those with medical indications. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) became available and recommended in the universal Italian infant immunization program. Since October 2012, indications for use of PCV13 were extended to subjects ≥ 50 y to prevent invasive pneumococcal diseases. The Italian decision makers should now revise regional indications for the prevention of pneumococcal diseases in the elderly. Pharmaco-economic analyses represent a useful tool to value the feasibility of new immunization programs and their sustainability. Therefore, an ad hoc population model was developed in order to value the clinical and economic impact of an adult pneumococcal vaccination program in Italy.   Particularly, different immunization scenarios were modeled: vaccination of 65 y-olds (1 cohort strategy), simultaneous vaccination of people aged 65 and 70 y (double cohort strategy) and, lastly, immunization of people aged 65, 70 and 75 y (triple cohort strategy), thus leading to the vaccination of 5, 10 and 15 cohorts during the 5 y of the program. In addition, the administration of a PPV23 dose one year after PCV13 was evaluated, in order to verify the economic impact of the supplemental serotype coverage in elderly people. The mathematical model valued the clinical impact of PCV13 vaccination on the number of bacteraemic pneumococcal pneumonia (BPP) and pneumococcal meningitis (PM) cases, and related hospitalizations and deaths. Although PCV13 is not yet formally indicated for the prevention of pneumococcal CAP by the European Medicine Agency (differently from FDA, whose indications include all pneumococcal diseases in subjects ≥ 50 y), the model calculated also the possible impact of vaccination on CAP cases (non-bacteraemic), considering the rate of this disease due to S. pneumoniae. The results of the analysis show that, in Italy, an age-based PCV13 vaccination program in elderly people is cost-effective from the payer perspective, with costs per QALY ranging from 17,000 to 22,000 Euro, according to the adopted vaccination strategy. The subsequent PPV23 offer results in an increment of costs per QALY (from 21,000 to 28,000 Euro, according to the vaccination strategy adopted). Pneumococcal vaccination using the conjugate vaccine turned out to be already favorable in the second year of implementation, with incremental costs per QALY comparable to those of other already adopted prevention activities in Italy (for instance, universal HPV vaccination of 12 y-old girls), with further benefits obtained when extending the study period beyond the 5-y horizon of our analysis.

Implantation of the common cavity malformation may prevent meningitis.

UNLABELLED: OBJECTIVES AND IMPORTANCE: Children with certain congenital malformations of the inner ear, including those with a common cavity defect, have a higher incidence of spontaneous cerebrospinal fluid (CSF) leak and resulting meningitis. However, they may also benefit from cochlear implantation. We suggest that surgical management may be possible that both prevents meningitis and provides hearing rehabilitation during the same procedure. CLINICAL PRESENTATION: A 2-year-old girl with bilateral common cavity defects who had previously undergone cochlear implantation developed contralateral CSF leak resulting in meningitis. INTERVENTION: After resolution of the infection, cochlear implantation was performed at the same time as definitive CSF leak repair. Simultaneous cochlear implantation and repair of the CSF leak successfully decreased the chance of recurrent meningitis in this case. She has been deriving hearing benefit from the bilateral implants. CONCLUSION: This case suggests a role for cochlear implantation to be combined with simultaneous CSF leak repair in children with a cochlear malformation. Furthermore, bilateral cochlear implantation at an early age may be warranted in these patients before CSF leaks and meningitis have occurred.

Invasive pneumococcal disease after routine pneumococcal conjugate vaccination in children, England and Wales.

We assessed known risk factors, clinical presentation, and outcome of invasive pneumococcal disease (IPD) in children 3-59 months of age after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in England and Wales. During September 2006-March 2010, a total of 1,342 IPD episodes occurred in 1,332 children; 14.9% (198/1,332) had comorbidities. Compared with IPD caused by PCV7 serotypes (44/248; 17.7%), comorbidities were less common for the extra 3 serotypes in the 10-valent vaccine (15/299; 5.0%) but similar to the 3 additional PCV13 serotypes (45/336; 13.4%) and increased for the 11 extra serotypes in 23-valent polysaccharide vaccine (PPV23) (39/186; 21.0%) and non-PPV23 serotypes (38/138; 27.5%). Fifty-two (3.9%) cases resulted from PCV7 failure; 9 (0.7%) case-patients had recurrent IPD. Case-fatality rate was 4.4% (58/1,332) but higher for meningitis (11.0%) and children with comorbidities (9.1%). Thus, comorbidities were more prevalent in children with IPD caused by non-PCV13 serotypes and were associated with increased case fatality.

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...

Optimizing pneumococcal vaccination for paediatric cochlear implant recipients using the cochlear implant pneumococcal vaccination flowchart.

INTRODUCTION: Cochlear implant recipients are known to be at an increased risk of meningitis. It is routine practice to check that pneumococcal vaccinations have been received prior to surgery. Recent changes in United Kingdom national guidelines mean that children who were previously thought to be fully immunized may in fact not be optimally protected. We present a simple, robust audit tool that can be used in both primary care and tertiary centres to identify those children at risk. METHODS: The pneumococcal immunization status of 63 paediatric cochlear implant recipients was assessed using a unique and comprehensive flowchart-style audit tool. The data collected included age at implantation, details of previous immunizations, and whether or not further vaccinations were required. RESULTS: Fifty-four per cent of children were not optimally immunized prior to implantation. Seventy per cent of children required further vaccinations following surgery. The commonest reason for an incomplete immunization history was failure to administer the 23-valent vaccine after the second birthday. CONCLUSION: The pneumococcal immunization schedule for high-risk children is complicated and nationally available guidance can be difficult to interpret. There are multiple types of vaccines and their use is not standardized across the UK. Cochlear implant programmes may find that a large proportion of their patients are in fact not optimally vaccinated, particularly in light of recent changes in the national guidelines. Our audit tool allows health professionals, in both primary care and implant centres, to accurately assess the status and immunization requirements for both new and old patients.