Modeling the cost-effectiveness of maternal acellular pertussis immunization (aP) in different socioeconomic settings: A dynamic transmission model of pertussis in three Brazilian states.

OBJECTIVES: Using dynamic transmission models we evaluated the health and cost outcomes of adding acellular pertussis (aP) vaccination of pregnant women to infant vaccination in three Brazilian states that represent different socioeconomic conditions. The primary objective was to determine whether the same model structure could be used to represent pertussis disease dynamics in differing socioeconomic conditions. METHODS: We tested three model structures (SIR, SIRS, SIRSIs) to represent population-level transmission in three socio-demographically distinct Brazilian states: São Paulo, Paraná and Bahia. Two strategies were evaluated: infant wP vaccination alone versus maternal aP immunization plus infant wP vaccination. Model projections for 2014-2029 include outpatient and inpatient pertussis cases, pertussis deaths, years of life lost, disability-adjusted life-years (DALYs) lost, and costs (in 2014 USD) of maternal aP vaccination, infant vaccination, and pertussis medical treatment. Incremental cost per DALY averted is presented from the perspective of the Brazilian National Health System. RESULTS: Based on goodness-of-fit statistics, the SIRSIs model fit best, although it had only a modest improvement in statistical quantitative assessments relative to the SIRS model. For all three Brazilian states, maternal aP immunization led to higher costs but also saved infant lives and averted DALYs. The 2014 USD cost/DALY averted was $3068 in Sao Paulo, $2962 in Parana, and $2022 in Bahia. These results were robust in sensitivity analyses with the incremental cost-effectiveness ratios exceeding per capita gross regional product only when the probability that a pertussis case is reported was assumed higher than base case implying more overt cases and deaths and therefore more medical costs. CONCLUSIONS: The same model structure fit all three states best, supporting the idea that the disease behaves similarly across different socioeconomic conditions. We also found that immunization of pregnant women with aP is cost-effective in diverse Brazilian states.

The data used to build the models: Pertussis morbidity and mortality burden considering various Brazilian data sources.

BACKGROUND: Pertussis is associated with significant disease burden in children worldwide. In addition to its cyclical nature, resurgences of pertussis cases, hospitalizations and deaths have been reported by many countries. We describe the dynamics of pertussis in Brazil, a middle-income country that has experienced a resurgence and that provides good quality data to allow building a dynamic transmission disease model. METHODS: We conducted a descriptive analysis of pertussis burden considering data from the national disease surveillance system, national hospitalization information system and national mortality registry. Study period was 2000-2016. Absolute numbers and rates per 100,000 inhabitants over time, by age sub-groups and geographical regions are presented. RESULTS: From 2000 to 2016, a total of 37,299 reported pertussis cases, 25,240 hospitalizations, and 601 deaths due to pertussis were reported. Although the outcomes - pertussis cases, hospitalizations, and deaths - come from independent information systems, our results document low disease burden with periodic increases every 3-4 years during the years 2000-2010, followed by a sharp increase which peaked in 2014. In both periods, disease burden is concentrated in young children, while its more serious outcomes - hospitalizations and deaths, are concentrated in infants. Pre-outbreak and outbreak disease burden as well as timing of peak during the outbreak period vary by states and within geographical regions, representing valuable resources of data for modelling purposes. CONCLUSION: Consistent disease burden patterns were observed over time in Brazil using a variety of data sources. Given the scarcity of good epidemiological data on pertussis available from low- and middle-income countries, our reported data provide valuable information for the assessment of the public health impact and cost-effectiveness modelling studies of newer strategies to prevent and control pertussis. These data were used to build and calibrate a national dynamic transmission model, which was used to evaluate the cost-effectiveness of maternal immunization. Clinical Trial registry name and registration number: Not applicable.

Cost-effectiveness of maternal pertussis immunization: Implications of a dynamic transmission model for low- and middle-income countries.

OBJECTIVE: This study evaluates the cost-effectiveness of maternal acellular pertussis (aP) immunization in low- and middle-income countries using a dynamic transmission model. METHODS: We developed a dynamic transmission model to simulate the impact of infant vaccination with whole-cell pertussis (wP) vaccine with and without maternal aP immunization. The model was calibrated to Brazilian surveillance data and then used to project health outcomes and costs under alternative strategies in Brazil, and, after adjusting model parameter values to reflect their conditions, in Nigeria and Bangladesh. The primary measure of cost-effectiveness is incremental cost (2014 USD) per disability-adjusted life-year (DALY). RESULTS: The dynamic model shows that maternal aP immunization would be cost-effective in Brazil, a middle-income country, under the base-case assumptions, but would be very expensive at infant vaccination coverage in and above the threshold range necessary to eliminate the disease (90-95%). At 2007 infant coverage (DTP1 90%, DTP3 61% at 1 year of age), maternal immunization would cost < $4,000 per DALY averted. At high infant coverage, such as Brazil in 1996 (DTP1 94%, DTP3 74% at 1 year), cost/DALY increases to $1.27 million. When the model's time horizon was extended from 2030 to 2100, cost/DALY increased under both infant coverage levels, but more steeply with high coverage. The results were moderately sensitive to discount rate, maternal vaccine price, and maternal aP coverage and were robust using the 100 best-fitting parameter sets. Scenarios representing low-income countries showed that maternal aP immunization could be cost-saving in countries with low infant coverage, such as Nigeria, but very expensive in countries, such as Bangladesh, with high infant coverage. CONCLUSION: A dynamic model, which captures the herd immunity benefits of pertussis vaccination, shows that, in low- and middle-income countries, maternal aP immunization is cost-effective when infant vaccination coverage is moderate, even cost-saving when it is low, but not cost-effective when coverage levels pass 90-95%.

Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H. influenzae type b in Brazil.

Following routine childhood vaccination against Haemophilus influenzae type b (Hib) disease in Brazil in 1999, passive laboratory surveillance reported increasing numbers of non-b serotypes and nontypeable H. influenzae (NTHi) from meningitis cases. To characterize this increase, we analyzed data on 3910 H. influenzae isolated from cerebrospinal fluid or blood from meningitis cases that were sent to the national reference laboratory for serotyping from 1990 to 2008. Hib accounted for 98% of H. influenzae meningitis isolates received during 1990-1999 versus 59% during 2000-2008, while non-b serotypes increased from 1% to 19% and NTHi increased from 2% to 22% of H. influenzae isolates received during the two periods. Higher proportions of non-b serotypes and NTHi than Hib were isolated from blood rather than cerebrospinal fluid. Estimated incidence rates for H. influenzae meningitis for Sao Paulo state remained below 1 case per million population during 2000-2008, although annual incidence of NTHi meningitis (mean, 0.03 cases per 100,000 population) increased in several age groups. Changes in surveillance for H. influenzae following introduction of Hib conjugate vaccine likely contributed to increased numbers of non-b and nontypeable H. influenzae meningitis isolates received at the national reference laboratory.

Selection of family 1 PspA molecules capable of inducing broad-ranging cross-reactivity by complement deposition and opsonophagocytosis by murine peritoneal cells.

PspA is one of the most well studied pneumococcal proteins and a promising candidate for a future protein-based anti-pneumococcal vaccine. Nevertheless, its structural and serological variability suggests the inclusion of more than one PspA molecule in order to broaden protection. Since different PspAs exhibit variable levels of cross-reactivity, the selection of the protein combination with the highest coverage potential is an essential step for PspA-based vaccine development. This work investigated the level of cross-reactivity within family 1 PspAs, and established a complement based antibody mediated opsonophagocytic assay for measuring the level of cross-protection. Among a panel of ten family 1 PspA molecules, two of them, one belonging to clade 1 and another from clade 2, induced antibodies capable of enhancing complement deposition and mediating the phagocytic killing by mouse peritoneal macrophages of all pneumococci bearing PspA family 1 strains tested, regardless of their serotype. Therefore, we suggest the inclusion of either one in a PspA-based vaccine, as a representative of family 1. Furthermore, our results suggest that opsonophagocytosis by mouse peritoneal cells can be an efficient means of evaluating the induction of protective immune responses in mice across a large number of strains.

Selection of family 1 PspA molecules capable of inducing broad-ranging cross-reactivity by complement deposition and opsonophagocytosis by murine peritoneal cells

PspA is one of the most well studied pneumococcal proteins and a promising candidate for a future protein-based anti-pneumococcal vaccine. Nevertheless, its structural and serological variability suggests the inclusion of more than one PspA molecule in order to broaden protection. Since different PspAs exhibit variable levels of cross-reactivity, the selection of the protein combination with the highest coverage potential is an essential step for PspA-based vaccine development. This work investigated the level of cross-reactivity within family 1 PspAs, and established a complement based antibody mediated opsonophagocytic assay for measuring the level of cross-protection. Among a panel of ten family 1 PspA molecules, two of them, one belonging to clade 1 and another from clade 2, induced antibodies capable of enhancing complement deposition and mediating the phagocytic killing by mouse peritoneal macrophages of all pneumococci bearing PspA family 1 strains tested, regardless of their serotype. Therefore, we suggest the inclusion of either one in a PspA-based vaccine, as a representative of family 1. Furthermore, our results suggest that opsonophagocytosis by mouse peritoneal cells can be an efficient means of evaluating the induction of protective immune responses in mice across a large number of strains.

An unusual presentation of leprosy at diagnosis: erythema multiforme-like type 2 reaction

Este estudo descreve um caso de Eritema Multiforme (EM) como a primeira manifestação clínica de Hanseníase (MH) em uma mulher de 35 anos. Quando atendida em um Hospital, a paciente apresentava febre, artralgia, e placas eritematosas em ambos os cotovelos e joelhos bilateralmente, algumas com bolhas e/ou necrose central. O diagnóstico foi confirmado por meio de biópsias de pele, que revelaram um padrão histopatológico compatível com EM, além da presença decélulas de Virchow e bacilos álcool-ácido resistentes (BAAR). Médicos em geral, especialmente os clínicos, devem considerar MH como diagnóstico diferencial de EM, especialmente em regiões endêmicas da doença.

This study describes a case of erythema multiforme (EM) as the first clinical manifestation of leprosy in a 35-year-old woman. She presented at the hospital with fever, arthralgia and erythematous plaques on both elbows and knees, some of them with bullous or necrotic center areas. The diagnosiswas confirmed by skin biopsy, which revealed a well-known EM pattern, and also showed the presence of Virchow cells and acid-fast bacilli. Physicians should be aware that leprosy must beconsidered in the differential diagnosis of EM, especially in endemic regions.

Non-typeable Streptococcus pneumoniae carriage isolates genetically similar to invasive and carriage isolates expressing capsular type 14 in Brazilian infants.

OBJECTIVES: We have recently found a high prevalence of non-typeable pneumococcal isolates (NTPn) circulating in day-care centers in Central Brazil, besides serotype 14 isolates. We therefore examined the genetic relationship among NTPn and serotype 14 from carriage and invasive pneumococcal isolates obtained from children attending emergency rooms enrolled in a population-based surveillance. METHODS: The isolates were characterized by Quellung reaction serotyping, PCR for the presence of pneumolysin and the loci for a capsule gene (cpsA) and the type 14 gene (cps14H) in all NTPn, and by multilocus sequence typing and pulsed field gel electrophoresis. RESULTS: 87.2% of the isolates were clustered into nine clusters. The major cluster included 41 pneumococcal serotype 14 (28 carriage and 13 invasive isolates) and two NTPn related to the global pneumococcal clone Spain(9V)-3. Overall, 95.4% of the NTPn carriage strains were genetically related to carriage or invasive strains expressing serotype 14. A dominant NTPn lineage was found, that grouped 14 pneumococcal strains. Almost half of the multidrug-resistant isolates grouped into the NTPn cluster. CONCLUSION: These findings provide baseline data to assess the impact of the pneumococcal vaccination on the molecular epidemiology of Streptococcus pneumoniae. Changes in frequency of NTPn isolates and also genetic changes should be carefully monitored post vaccination, to detect potential vaccine-escape or replacement disease by capsule switched strains, especially in areas where colonization with NTPn has been frequently observed.

Immunization of mice with single PspA fragments induces antibodies capable of mediating complement deposition on different pneumococcal strains and cross-protection.

PspA is an important candidate for a vaccine with serotype-independent immunity against pneumococcal infections. Based on sequence relatedness, PspA has been classified into three families comprising six clades. We have previously addressed the cross-reactivity of antibodies against PspA fragments containing the N-terminal and proline-rich regions of PspA from clades 1 to 5 (PspA1, PspA2, PspA3, PspA4, and PspA5) by Western blot analysis and reported that anti-PspA4 and anti-PspA5 were able to recognize pneumococci expressing PspA proteins from all of the clades analyzed. We have now analyzed the functional capacity of these antibodies to bind and to mediate complement deposition on intact bacteria in vitro. Our results show that both PspA4 and PspA5 elicit antibodies that are able to bind and to mediate complement deposition efficiently on pneumococcal strains bearing PspA proteins from clades 1 to 5. Moreover, mice immunized with PspA4 and PspA5 were protected against an intranasal lethal challenge with strains expressing PspA proteins from the two major families. PspA4 and PspA5 are thus able to induce antibodies with a high degree of cross-reactivity in vitro, which is reflected in cross-protection of mice. We have also analyzed the contribution of the nonproline (NonPro) block within the conserved proline-rich region to the reactivity of anti-PspA antibodies, and the results indicate that N-terminal alpha-helical region, the blocks of proline repeats, and the NonPro region can influence the degree of cross-reactivity of antibodies to PspA.

Survey of nonsusceptible nasopharyngeal Streptococcus pneumoniae isolates in children attending day-care centers in Brazil.

A survey of nasopharyngeal carriage of penicillin nonsusceptible pneumococcal (PNSp) isolates was conducted among 1192 children attending 62 day care centers in Brazil, where pneumococcal vaccination has not been routinely introduced. Nasopharyngeal pneumococcal carriage was detected in 686 (57.6%) infants, and 178 (25.9%) of them carried PNSp isolates. Being less than 24 months of age, hospitalization in the previous 3 months, and recurrent acute otitis media were independently associated with PNSp. Serotypes 14, 23F, 19A, 6A, 6B and 19F were the most common serotype isolated accounting for 80% of the PNSp. A high proportion (35/332) of non-(sero)typeable isolates was detected, 62.9% of them PNSp. Serotypes coverage projected for the pneumococcal conjugate vaccine (PCV) 13-valent vaccine (72%) was significantly higher compared with PCV7 (58.4%) and PCV 10-valent vaccine (59.3%).

Spatial clusters of violent deaths in a newly urbanized region of Brazil: highlighting the social disparities.

BACKGROUND: Deaths due to homicides and traffic accidents among youth are a public health issue worldwide. Studies of the complex network of cause and effect on this topic point to both poverty and health inequalities. Different investigational approaches to intentional and unintentional deaths combined with socioeconomic variables can help create a better understanding of the association between violence and socioeconomic conditions. This study analyzed the spatial distribution and potential clusters of risk for intentional and unintentional deaths among youths aged 15-24 years in Goiânia, a newly urbanized city in central Brazil. METHODS: Death data and residential addresses were extracted from the national Mortality Information System and validated by household visits. To detect all potential cases, we prospectively investigated every death classified as a transport accident, assault, legal intervention, intentional self-harm, unknown underlying cause, and undetermined intent according to the ICD-10.The Geographical Information System was used to plot residential addresses, and cases were interactively geocoded to the residential address level using a digital map of the municipality. Spatial scan statistic was applied (Poisson model) to identify clusters of census tracts with high mortality due to intentional injuries and traffic accidents. The socioeconomic variables obtained using census data were compared between the most likely cluster and other areas of the municipality. RESULTS: The most violent deaths among young people were due to intentional injuries. Between August 2005 and August 2006, 145 addresses for cases of intentional injuries and traffic accidents were located and geocoded. No significant clusters for deaths due to traffic accidents were found within the municipality. One significant cluster (RR = 4.65; p = 0.029) composed of 14 cases of intentional deaths, mostly homicides, was detected in an emergent, populated, and very poor area on the outskirts of the town. This cluster had a significantly higher proportion of people with the lowest educational status, lowest income, and poor housing conditions in comparison to the remainder of the municipality. CONCLUSION: Our findings highlight the link between social inequalities and intentional deaths, clearly showing the need for urgent social interventions to reduce violence and premature mortality.

Estimating the cost-effectiveness of pneumococcal conjugate vaccination in Brazil / Cálculo de la relación costo-efectividad de la vacuna conjugada antineumocócica en Brasil

OBJECTIVE: To compare the costs and benefits of pneumococcal conjugate vaccination compared with no vaccination from the perspectives of the health care system and society. METHODS: Using data from established sources, we estimated the incidence and mortality due to invasive pneumococcal disease, pneumonia, and acute otitis media (AOM) for a hypothetical birth cohort of children from birth to 5 years. RESULTS: A universal pneumococcal conjugate vaccination program was estimated capable of annually avoiding 1 047 cases of invasive disease, 58 226 cases of pneumonia, and 209 862 cases of AOM. When herd immunity effects were considered, the program prevented 1.3 million cases of pneumococcal disease and over 7 000 pneumococcal deaths. At a vaccination cost of R$ 51.12 (US$ 26.35) per dose, vaccination would cost annually R$ 4 289 (US$ 2,211) per disability-adjusted life years averted. This does not take into account herd immunity effects. CONCLUSIONS: At the current vaccine price, conjugate vaccination could be a cost-effective investment compared to other options to control childhood diseases. Further analysis is required to determine whether vaccination at the current price is affordable to Brazil.

OBJETIVO: Comparar los costos y los beneficios de la aplicación de la vacuna conjugada antineumocócica en comparación con la no vacunación, desde las perspectivas del sistema de salud y la sociedad. MÉTODOS: A partir de fuentes reconocidas, se estimaron la incidencia y la mortalidad por enfermedad neumocócica invasora, neumonía y otitis media aguda (OMA) para una cohorte hipotética de niños desde su nacimiento hasta los 5 años. RESULTADOS: Se estimó que un programa de vacunación universal con una vacuna conjugada antineumocócica sería capaz de evitar anualmente 1 047 casos de la enfermedad invasora, 58 226 casos de neumonía y 209 862 casos de OMA. Si se considera el efecto de la inmunidad de grupo, el programa evitaría 1,3 millones de casos de enfermedad y más de 7 000 muertes por infección neumocócica. A R$ 51,12 (US$ 26,35) por dosis, la vacunación costaría anualmente R$ 4 286 (US$ 2,211) por cada año de vida ajustado por discapacidad evitado, sin tomar en cuenta el efecto de la inmunidad de grupo. CONCLUSIONES: En comparación con otras opciones de control de estas enfermedades infantiles y con los precios actuales de la vacuna conjugada, la vacunación antineumocócica podría ser una inversión efectiva en función del costo. Se requieren más estudios para determinar si la vacunación es costeable para Brasil a los precios actuales.

Estimating the cost-effectiveness of pneumococcal conjugate vaccination in Brazil.

OBJECTIVE: To compare the costs and benefits of pneumococcal conjugate vaccination compared with no vaccination from the perspectives of the health care system and society. METHODS: Using data from established sources, we estimated the incidence and mortality due to invasive pneumococcal disease, pneumonia, and acute otitis media (AOM) for a hypothetical birth cohort of children from birth to 5 years. RESULTS: A universal pneumococcal conjugate vaccination program was estimated capable of annually avoiding 1 047 cases of invasive disease, 58 226 cases of pneumonia, and 209 862 cases of AOM. When herd immunity effects were considered, the program prevented 1.3 million cases of pneumococcal disease and over 7 000 pneumococcal deaths. At a vaccination cost of R$ 51.12 (US$ 26.35) per dose, vaccination would cost annually R$ 4 289 (US$ 2,211) per disability-adjusted life years averted. This does not take into account herd immunity effects. CONCLUSIONS: At the current vaccine price, conjugate vaccination could be a cost-effective investment compared to other options to control childhood diseases. Further analysis is required to determine whether vaccination at the current price is affordable to Brazil.

Recognition of pneumococcal isolates by antisera raised against PspA fragments from different clades.

Pneumococcal surface protein A (PspA) is an important vaccine candidate against pneumococcal infections, capable of inducing protection in different animal models. Based on its structural diversity, it has been suggested that a PspA-based vaccine should contain at least one fragment from each of the two major families (family 1, comprising clades 1 and 2, and family 2, comprising clades 3, 4 and 5) in order to elicit broad protection. This study analysed the recognition of a panel of 35 pneumococcal isolates bearing different PspAs by antisera raised against the N-terminal regions of PspA clades 1 to 5. The antiserum to PspA clade 4 was found to show the broadest cross-reactivity, being able to recognize pneumococcal strains containing PspAs of all clades in both families. The cross-reactivity of antibodies elicited against a PspA hybrid including the N-terminal region of clade 1 fused to a shorter and more divergent fragment (clade-defining region, or CDR) of clade 4 (PspA1-4) was also tested, and revealed a strong recognition of isolates containing clades 1, 4 and 5, and weaker reactions with clades 2 and 3. The analysis of serum reactivity against different PspA regions further revealed that the complete N-terminal region rather than just the CDR should be included in an anti-pneumococcal vaccine. A PspA-based vaccine is thus proposed to be composed of the whole N-terminal region of clades 1 and 4, which could also be expressed as a hybrid protein.

Prevalence and risk factors for nasopharyngeal carriage of Streptococcus pneumoniae among adolescents.

Data on the prevalence of pneumococcal nasopharyngeal carriage and its risk factors among adolescents are scarce. The aim of this study was to provide such information. A cross-sectional, population-based prospective study was conducted. Participants were 1013 adolescents (age range 10-19 years) randomly recruited in 22 public schools. Those schools were randomly chosen among 307 public schools from 11 Sanitary Districts of Salvador, Brazil. Nasopharyngeal samples were assessed by standard procedures to recover and identify Streptococcus pneumoniae. Data on potential risk factors were gathered by confidential interview based on a standardized questionnaire. Pneumococci were recovered from 8.2 % [83/1013, 95 % confidence interval (CI) 6.6-10.0]. By stepwise logistic regression, pneumococcal colonization was independently associated with younger age [odds ratio (OR) 0.85, 95 % CI 0.77-0.94, P=0.001], being male (OR 1.78, 95 % CI 1.11-2.85, P=0.02), exposure to passive smoke in the household (OR 1.76, 95 % CI 1.10-2.79, P=0.02), having an upper respiratory infection during recruitment (OR 2.67, 95 % CI 1.67-4.28, P<0.001) and having a history involving an episode of acute asthma during the last year (OR 2.89, 95 % CI 1.18-7.08, P=0.03). The estimated probability of pneumococcal colonization decreased with age (chi(2) for trend=8.52, P=0.003). These findings provide tools for increasing the use of prevention strategies for pneumococcal diseases, such as pneumococcal vaccination among asthmatic patients and public health measures to stop smoking.

Computer-aided diagnosis in chest radiography for detection of childhood pneumonia.

OBJECTIVES: This article presents a novel approach based on computer-aided diagnostic (CAD) scheme and wavelet transforms to aid pneumonia diagnosis in children, using chest radiograph images. The prototype system, named Pneumo-CAD, was designed to classify images into presence (PP) or absence of pneumonia (PA). MATERIALS AND METHODS: The knowledge database for the Pneumo-CAD comprised chest images confirmed as PP or PA by two radiologists trained to interpret chest radiographs according to the WHO guidelines for the diagnosis of pneumonia in children. The performance of the Pneumo-CAD was evaluated by a subset of images randomly selected from the knowledge database. The retrieval of similar images was made by feature extraction using wavelets transform coefficients of the image. The energy of the wavelet coefficients was used to compose the feature vector in order to support the computational classification of images as PP or PA. Methodology I worked with a rank-weighted 15-nearest-neighbour scheme, while methodology II employed a distance-dependent weighting for image classification. The performance of the prototype system was assessed by the ROC curve. RESULTS: Overall, the Pneumo-CAD using the Haar wavelet presented the best accuracy in discriminating PP from PA for both, methodology I (AUC=0.97) and methodology II (AUC=0.94), reaching sensitivity of 100% and specificity of 80% and 90%, respectively. CONCLUSION: Pneumo-CAD could represent a complementary tool to screen children with clinical suspicion of pneumonia, and so to contribute to gather information on the burden of-pneumonia estimates in order to help guide health policies toward preventive interventions.

Genetic diversity of PspA types among nasopharyngeal isolates collected during an ongoing surveillance study of children in Brazil.

Pneumococcal surface protein A (PspA) has been considered a potential candidate for human vaccines because of its serotype-independent protective immunity. Nasopharyngeal (NP) pneumococcal colonization is highly prevalent in infants and precedes the invasive disease. Thus, prevention of NP colonization may reduce the burden of pneumococcal disease in children. Scarce information focusing on PspA from pneumococcal carriage in humans is available. We examined the genetic diversity of PspA from NP isolates obtained during an ongoing pneumococcal surveillance study with children. PspA families and clades of 183 community-acquired Streptococcus pneumoniae NP isolates from healthy children (n = 97) and children with respiratory tract infections (n = 48), pneumonia (n = 33), or meningitis (n = 5) were investigated. Overall, 79.8% (n = 146) of the pneumococcal isolates were classified as PspA family 1 (35.5%) and family 2 (44.3%), whereas 20.2% of the isolates could not be typed. The distribution of PspA families and clades did not differ significantly according to the clinical status of the children. A dendrogram comparing the genetic relationship between the amino acid sequences of the clade-defining region of PspA from NP strains together with 24 invasive reference strains (GenBank) closely reproduced the profile of the families and clades previously reported for pneumococcal invasive strains. These findings strengthen the idea that the use of PspA as a vaccine antigen may protect children against carriage as well as invasive pneumococcal disease.

Haemophilus influenzae type b vaccination: long-term protection.

OBJECTIVE: To identify evidence of the impact of Haemophilus influenzae type b (Hib) conjugate vaccine on the epidemiology of invasive Hib disease. SOURCES OF DATA: This review was based on a search of MEDLINE, LILACS, technical reports, national and international guidelines (publications from 1991 to 2005). The keywords Haemophilus influenzae type b, immunization, impact, and effectiveness, alone or in combination, were used to retrieve the articles. Studies published before 1991 and cited in the references of the studies reviewed were analyzed for useful information. SUMMARY OF THE FINDINGS: Introduction of the Hib conjugate vaccine produced great decline in the incidence of invasive Hib disease in childhood in countries where this vaccine was introduced into the routine immunization schedule. Nevertheless, the resurgence of invasive Hib disease in some regions has challenged several researchers to identify the reasons for this epidemiological pattern, as well as the measures to be implemented in order to avoid such a phenomenon. CONCLUSIONS: The use of Hib conjugate vaccine on a population scale has been greatly effective; nonetheless, changes in the vaccination scheme seem to be necessary to keep invasive Hib disease under control.

Vacinação contra Haemophilus influenzae tipo b: proteção a longo prazo / Haemophilus influenzae type b vaccination: long term protection

OBJETIVO: Identificar as evidências sobre o impacto da vacina conjugada para Haemophilus influenzae tipo b (Hib) na epidemiologia da doença invasiva por Hib. FONTE DOS DADOS: Pesquisa nas bases de dados do MEDLINE, LILACS, publicações técnicas de organizações internacionais, diretrizes nacionais e internacionais, nos últimos 15 anos (1991-2005), utilizando os seguintes unitermos: Haemophilus influenzae type b, immunization, impact, effectiveness. Foram incluídas as publicações que apresentaram informação para atender o objetivo deste artigo. Artigos publicados em período anterior ao da pesquisa e citados em referências dos artigos incluídos foram analisados quanto à apresentação de informação de interesse. SíNTESE DOS DADOS: A introdução da vacina conjugada para Hib produziu grande declínio na incidência de casos de doença invasiva por Hib nos diversos países em que seu uso foi incorporado à rotina de vacinação das crianças. No entanto, o ressurgimento de casos com doença invasiva por Hib tem mobilizado vários investigadores na busca das possíveis explicações para esses eventos, bem como a identificação das medidas a serem implementadas para evitar o reaparecimento da doença. CONCLUSÕES: O uso da vacina conjugada para Hib em escala populacional tem sido extremamente efetivo. No entanto, mudanças no esquema vacinal poderão ser necessárias para a manutenção do controle da doença invasiva por Hib, frente ao atual cenário epidemiológico das infecções pelo Hib.

Antimicrobial resistance and serotypes of nasopharyngeal strains of Streptococcus pneumoniae in Brazilian adolescents.

The aim of this study was to describe the frequency of antimicrobial-resistance and serotypes of nasopharyngeal pneumococcal isolates from adolescents. Clinical data and nasopharyngeal specimens for culture were collected from 1,013 adolescents as a part of a population-based study. A total of 83 isolates of Streptococcus pneumoniae were identified (8.2%). Seventy-four of the 83 isolates were serotyped. The median age of the 83 adolescents colonized by pneumococci was 14 years (mean 14 +/- 2.2 yrs); 55.4% were males. Intermediate resistance to penicillin was detected in 7.2% (6/83). No strain showed high resistance to penicillin. All isolates were susceptible to clindamycin, chloramphenicol, rifampin, and vancomycin; 37.3%, 18.1%, and 4.8% were resistant to trimethoprim-sulfamethoxazole, tetracycline, and erythromycin, respectively. The most frequent serotypes (5-10% of strains each) were 6B, 6A, 23F, and 18C among 28 serotypes/serogroups identified; 18.9% of the strains were nontypeable (NT). Intermediate resistance to penicillin was detected in serotypes 6B, 14, and NT. The rate of resistance to penicillin of nasopharyngeal isolates is low considering data from other studies about invasive strains recovered from children in Brazil. Serotype patterns are similar, except for type 14, which was unusually infrequent.