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Early impact of 10-valent pneumococcal conjugate Vaccine, Amsterdam in childhood pneumonia hospitalizations using primary data from an active population-based surveillance
(2016) Andrade, Sabrina Sgambatti de; Minamisava, Ruth; Bierrenbach, Ana Luiza de Souza; Toscano, Cristiana Maria; Vieira, Maria Aparecida da Silva; Policena, Gabriela Moreira; Andrade, Ana Lúcia Sampaio Sgambatti de
Background In Brazil, 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in 2010 in the childhood routine immunization program. We used primary data to evaluate the effect of PCV10 on the reduction of hospital admissions due to community-acquired pneumonia (CAP). Methods Active population-based surveillance studies on pneumonia hospitalizations in children aged <36 months were conducted before and after PCV10 introduction in Central Brazil. The surveillances comprised all 17 pediatric hospitals of the study area, which provide assistance for public and private health insurances. Linear regression was performed to detect any trend in pneumonia monthly rates previously to vaccine introduction. PCV10 post-vaccination impact (Nov/2011 to Oct/2013) on clinical and X-Ray confirmed pneumonia was estimated as the relative and the absolute reduction (prevented burden) in pneumonia admission rates, taking as baseline the pre-vaccination period (May/2007 to Apr/2009). Results Overall, males presented higher rates of pneumonia hospitalization, compared to females. The relative rate reduction for clinical and X-Ray confirmed pneumonia was 13.1%, and 25.4%, respectively for children aged 2–23 months. The highest prevented burden was observed in age-groups 2–11 months, respectively 853/100,000 (from 6788/100,000 to 5935/100,000), and 729/100,000 (from 2871/100,000 to 2142/100,000), for clinical and X-Ray confirmed pneumonia. Conclusions This study provides evidence for the impact of PCV10 in clinical and X-Ray confirmed pneumonia in routine vaccination program in Brazil, after 3 years of vaccine introduction. Extended follow-up studies should confirm the benefit of vaccination through herd effect given the high burden of pneumonia in our setting.
Increased risk of death and readmission after hospital discharge of critically ill patients in a developing country: a retrospective multicenter cohort study
(2018) Lima, Vanessa Chaves Barreto Ferreira de; Bierrenbach, Ana Luiza de Souza; Alencar, Gizelton Pereira; Andrade, Ana Lúcia Sampaio Sgambatti de; Azevedo, Luciano Cesar Pontes de
Purpose To describe long-term mortality and hospital readmissions of patients admitted to Brazilian intensive care units (ICU). Methods Retrospective cohort study of adult patients admitted to Brazilian hospitals affiliated to the Public Healthcare System from 10 state capitals. ICU patients were paired to non-ICU patients by frequency matching (ratio 1:2), according to postal code and admission semester. Hospitalization records were linked through deterministic linkage to national mortality data. Primary outcome was mortality up to 1 year. Other outcomes were mortality and readmissions at 30 and 90 days and 3 years. Multiple Cox regressions were used adjusting for age, sex, cancer diagnosis, type of hospital, and surgical status. Results We included 324,594 patients (108,302 ICU and 216,292 non-ICU). ICU patients had increased hospital length of stay [9 (5–17) vs. 3 (1–6) days, p < 0.001] and mortality (18.5 vs. 3.6%, p < 0.001) versus non-ICU patients. One year after discharge, ICU patients were more frequently readmitted to hospital (25.4 vs. 17.4%, p < 0.001) and to ICU (31.4 vs. 7.3%, p < 0.001) than controls. Mortality up to 1 year was also higher for ICU patients (14.3 vs. 3.9%, p < 0.001). A significant interaction between surgical status and mortality was found, with adjusted hazard ratios (HRs) up to 1 year of 2.7 [95% confidence interval (CI) 2.5–2.9] for surgical patients, and 3.4 (95%CI 3.3–3.5) for medical patients. The risk for death and readmission diminished over time up to 3 years. Conclusions In a public healthcare system of a developing country, ICU patients have excessive long-term mortality and frequent readmissions. The ICU burden tended to reduce over time after hospital discharge.
Correction models of pneumonia mortality rates in the elderly in Brazil from 2005 to 2016
(2020) Miranda, Denismar Borges de; Policena, Gabriela Moreira; Minamisava, Ruth; Bierrenbach, Ana Luiza de Souza; Andrade, Ana Lúcia Sampaio Sgambatti de; Morais Neto, Otaliba Libânio de
Objective: To estimate the burden of pneumonia (PNM) mortality in the elderly in Brazil using different methodologies for rate correction. Method: A time-series study of mortality rates from PNM in the elderly from 2005- 2016. For the correction of the rates, two strategies were used: 1-correction by active search (CBA) and 2-correction by active search more redistribution (CBAR). In addition, a methodology for comparing corrected rates, calculated lower respiratory tract infection rates (ITRi) using estimates from the Global Burden Disease study. Trend was assessed using regression models. Result: From 2005 to 2016, 546,068 deaths were registered, which, after using the CBAR correction strategy, left 501,380, a reduction of 8.2%. There was an increasing trend of PNM mortality rates for all regions of Brazil and for the elderly population. The largest linear increase in mortality rate due to CBAR pneumonia was observed in the Northeast. Conclusion: These estimates of the magnitude and trend presented make it possible to analyze the behavior of mortality rates due to pneumonia in the elderly in Brazil and to subsidize the National Immunization Program on the need to include a specific pneumococcal vaccine for the entire elderly population.
Qualifying information on deaths and serious injuries caused by road traffic in five Brazilian capitals using record linkage
(2017) Mandacaru, Polyana Maria Pimenta; Andrade, Ana Lúcia Sampaio Sgambatti de; Rocha, Marli Souza; Aguiar, Fernanda Pinheiro; Nogueira, Maria Sueli M.; Girodo, Anne Marielle; Pedrosa, Ana Amélia Galas; Oliveira, Vera Lídia Alves de; Alves, Marta Maria Malheiros; Paixão, Lúcia Maria Miana Mattos
Introduction Road traffic crashes (RTC) are an important public health problem, accounting for 1.2 million deaths per year worldwide. In Brazil, approximately 40,000 deaths caused by RTC occur every year, with different trends in the Federal Units. However, these figures may be even greater if health databases are linked to police records. In addition, the linkage procedure would make it possible to qualify information from the health and police databases, improving the quality of the data regarding underlying cause of death, cause of injury in hospital records, and injury severity. Objective This study linked different data sources to measure the numbers of deaths and serious injuries and to estimate the percentage of corrections regarding the underlying cause of death, cause of injury, and the severity injury in victims in matched pairs from record linkage in five representative state capitals of the five macro-regions of Brazil. Methods This cross-sectional, population-based study used data from the Hospital Information System (HIS), Mortality Information System (MIS), and Police Road Traffic database of Belo Horizonte, Campo Grande, Curitiba, Palmas, and Teresina, for the year 2013 for Teresina, and 2012 for the other capitals. RecLink III was used to perform probabilistic record linkage by identifying matched pairs to calculate the global correction percentage of the underlying cause of death, the circumstance that caused the road traffic injury, and the injury severity of the victims in the police database. Results There was a change in the cause of injury in the HIS, with an overall percentage of correction estimated at 24.4% for Belo Horizonte, 96.9% for Campo Grande, 100.0% for Palmas, and 33.2% for Teresina. The overall percentages of correction of the underlying cause of death in the MIS were 29.9%, 11.9%, 4.2%, and 33.5% for Belo Horizonte, Campo Grande, Curitiba, and Teresina, respectively. The correction of the classification of injury severity in police database were 100.0% for Belo Horizonte and Teresina, 48.0% for Campo Grande, and 51.4% for Palmas after linkage with hospital database. The linkage between mortality and police database found a percentage of correction of 29.5%, 52.3%, 4.4%, 74.3 and 72.9% for Belo Horizonte, Campo Grande, Palmas, Curitiba and Teresina, respectively in the police records. Conclusions The results showed the importance of linking records of the health and police databases for estimating the quality of data on road traffic injuries and the victims in the five capital cities studied. The true causes of death and degrees of severity of the injuries caused by RTC are underestimated in the absence of integration of health and police databases. Thus, it is necessary to define national rules and standards of integration between health and traffic databases in national and state levels in Brazil.
Direct and indirect impact of 10-valent pneumococcal conjugate vaccine introduction on pneumonia hospitalizations and economic burden in all age-groups in Brazil: a time-series analysis
(2017) Andrade, Ana Lúcia Sampaio Sgambatti de; Afonso, Eliane Terezinha; Minamisava, Ruth; Bierrenbach, Ana Luiza de Souza; Broche Cristo, Elier; Morais Neto, Otaliba Libânio de; Policena, Gabriela Moreira; Domingues, Carla Magda Allan Santos; Toscano, Cristiana Maria
Combined effect of PCV10 and meningococcal C conjugate vaccination on meningitis mortality among children under five years of age in Brazil
(2018) Bierrenbach, Ana Luiza de Souza; Minamisava, Ruth; Alencar, Airlane Pereira; Alencar, Gizelton Pereira; Andrade, Ana Lúcia Sampaio Sgambatti de
The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in the Brazilian National Immunization Program in March 2010, scheduled at 2, 4, and 6 months, with a booster at 12–15 months of age. The meningococcal C conjugate vaccine (MCC) was introduced in November 2010, scheduled at 3 and 5 months, with a booster dose at 12–15 months of age and no catch-up for older age groups. In this interrupted time-series analysis study, we used Brazilian mortality data from 2005 to 2015 for children under five years of age (excluding data from the state of Bahia) to assess the combined impact of these vaccines on the overall burden of meningitis mortality among children aged 0–23 months and 2–4 years, as defined using meningitis and meningococcemia specific International Classification of Diseases - tenth revision codes. Secular trends and seasonality were taken into account. We found significant reductions for both age groups relative to those observed for the comparison group of diseases, with immediate effects after the transition period (2010-2011) of 29.2% and 27.5% for children aged 0–23 months and 2–4 years, respectively. These immediate effects were sustained throughout the post-vaccination period (2012–2015). In total, 337 deaths were averted by the combined effect of both vaccines, 238 (95%CI 169- 319) for children aged 0–23 months and 99 (95%CI 56–144) for those aged 2–4 years. These results add strong evidence in support of investments in these vaccines by low and middle-income countries.
Cost of management of severe pneumonia in young children: systematic analysis
(2016) Shanshan, Zhang; Sammon, Peter M.; Andrade, Ana Lúcia Sampaio Sgambatti de; Toscano, Cristiana Maria; Nunes , Sheila Elke Araujo; Sinha, Anushua; Madhi, Shabir A.; Khandaker, Gulam; Jiehui , Kevin Yin
Background Childhood pneumonia is a major cause of childhood illness and the second leading cause of child death globally. Understanding the costs associ ated with the management of childhood pneumonia is essential for resource allocation and priority setting for child health. Methods We conducted a systematic review to iden tify studies reporting data on the cost of management of pneumonia in children younger than 5 years old. We collected unpublished cost data on non–severe, severe and very severe pneumonia through collabora tion with an international working group. We extract ed data on cost per episode, duration of hospital stay and unit cost of interventions for the management of pneumonia. The mean (95% confidence interval, CI) and median (interquartile range, IQR) treatment costs were estimated and reported where appropriate. Results We identified 24 published studies eligible for inclusion and supplemented these with data from 10 unpublished studies. The 34 studies included in the cost analysis contained data on more than 95000 chil dren with pneumonia from both low– and–middle in come countries (LMIC) and high–income countries (HIC) covering all 6 WHO regions. The total cost (per episode) for management of severe pneumonia was US$ 4.3 (95% CI 1.5–8.7), US$ 51.7 (95% CI 17.4– 91.0) and US$ 242.7 (95% CI 153.6–341.4)–559.4 (95% CI 268.9–886.3) in community, out–patient fa cilities and different levels of hospital in–patient set tings in LMIC. Direct medical cost for severe pneumo nia in hospital inpatient settings was estimated to be 26.6%–115.8% of patients’ monthly household in come in LMIC. The mean direct non–medical cost and indirect cost for severe pneumonia management ac counted for 0.5–31% of weekly household income. The mean length of stay (LOS) in hospital for children with severe pneumonia was 5.8 (IQR 5.3–6.4) and 7.7 (IQR 5.5–9.9) days in LMIC and HIC respectively for these children. Conclusion This is the most comprehensive review to date of cost data from studies on the management of childhood pneumonia and these data should be help ful for health services planning and priority setting by national programmes and international agencies.
Reduction in all-cause otitis media-related outpatient visits in children after PCV10 introduction in Brazil
(2017) Sartori, Ana Lucia; Minamisava, Ruth; Bierrenbach, Ana Luiza de Souza; Toscano, Cristiana Maria; Afonso, Eliane Terezinha; Morais Neto, Otaliba Libânio de; Antunes, José Leopoldo Ferreira; Broche Cristo, Elier; Andrade, Ana Lúcia Sampaio Sgambatti de
Few studies have reported the effect of 10-valent pneumococcal conjugate vaccine (PCV10) on otitis media (OM) in infants. In particular, no population-based study in upper-middle income countries is available. In 2010, Brazil introduced PCV10 into its routine National Immunization Program using a 3+1 schedule. We measured the impact of PCV10 on all-cause OM in children. An interrupted time-series analysis was conducted in Goiânia/Brazil considering monthly rates (per 100,000) of all-cause OM outpatient visits in children aged 2–23 months. We used case-based data from the Outpatient Visits Information System of the Unified Health System coded for ICD-10 diagnosis for the period of August/2008 to July/2015. As a comparator, we used rates of outpatient visits due to all-other causes. The relative reduction of all-cause OM and all-other causes of outpatient visits were calculated as the difference between the predicted and observed cumulative rates of the PCV10 post-vaccination period. We then subtracted the relative reduction of all-other causes of outpatient visits from all-cause OM to obtain the impact of PCV10 on OM. In total, 6,401 OM outpatient visits were recorded in 4,793 children aged 2–23 months. Of these, 922 (19.2%) children had more than one OM episode. A significant reduction in all-cause OM visits was observed (50.7%; 95%CI: 42.2–59.2%; p = 0.013), while the reduction in visits due to all-other causes was 7.7% (95% CI 0.8–14.7%; p<0.001). The impact of PCV10 on all-cause OM was thus estimated at 43.0% (95%CI 41.4–44.5). This is the first study to show significant PCV10 impact on OM outpatient visits in infants in a developing country. Our findings corroborate the available evidence from developed countries.
Regional disparities in road traffic injuries and their determinants in Brazil, 2013
(2016) Morais Neto, Otaliba Libânio de; Andrade, Ana Lúcia Sampaio Sgambatti de; Guimarães, Rafael Alves; Mandacarú, Polyana Maria Pimenta; Tobias, Gabriela Camargo
Background: In recent decades middle-income countries have experienced a rapid increase in the number of cars and motorcycles. Increased deaths and hospitalizations due to road traffic injuries (RTI) has been observed in several countries as a result. In this study we assessed the determinants of RTIs in Brazil by mode of transportation and compared differences in RTI rates among macro-regions. Methods: We used data from the National Health Survey (NHS) conducted in 2013 by the Brazilian Institute of Geography and Statistics and the Ministry of Health. NHS is a comprehensive household survey which includes a representative sample (N = 60,198) of individuals aged 18 years or older. The prevalence and determinants of RTI were estimated according to different modes of transport (car/van, motorcycle, and other) and regions of the country. Bivariate and multivariable logistic regression models were applied to assess crude and adjusted odds ratios, respectively, and their 95 % CI for RTI determinants. Results: The prevalence of RTI for the Southeast, South, Central-West, Northeast and North regions of Brazil was 2.4 %, 2.9 %, 4.4 %, 3.4 % and 4.8 %, respectively, pointing to important differences among regions. High percentages of motorcyclists were observed in the Northeast and North regions. For motorcyclists, factors associated with RTIs were being male (OR = 2.6;95 % CI:2.3;3.0), aged 18–29 (OR = 3.2; 95 % CI:2.7;3.8) and 30–39 years (OR = 2.0;95 % CI:1.7;2.5), black (OR = 1.4;95 % CI:1.1;1.7), having elementary educational (OR = 1.5;95 % CI:1.1;1.9), reporting binge drinking behavior (OR = 1.3;95 % CI:1.1;1.5), and living in the Central-West (OR = 2.0;95 % CI:1.6;2.5), Northeast (OR = 1.8;95 % CI: 1.5;2.1) and North (OR = 2.0;95 % CI:1.6; 2.5) regions of the country. The independent variables associated with RTI for car/van occupants were being male (OR = 1.7;95 % CI:1.4;2.1), aged 18–29 (OR = 1.5;95 % CI:1.1;2.0) and 30–39 years (OR = 2.5;95 % CI:1.9;3.2), reporting binge drinking behavior (OR = 2.0;95 % CI:1.6;2.5) and living in the South region (OR = 1.6;95 % CI:1.3;2.1). Conclusions: There were considerable regional disparities in RTI rates across Brazil’s regions. Motorcyclists contributed to the high RTI rates in these regions as did demographic factors and behaviors such as alcohol use. These findings can help guide interventions to reduce the burden of RTIs in Brazil.
Effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae among children in São Paulo, Brazil
(2016) Brandileone, Maria Cristina de Cunto; Ramos, Rosemeire Cobo Zanella; Almeida, Samanta Cristine Grassi; Brandão, Angela Pires; Ribeiro, Ana Freitas
In March 2010, Brazil introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in the routine infant immunization program using a 4-dose schedule and catch-up for children <23 months. We inves tigated PCV10 effect on nasopharyngeal carriage with vaccine-type Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) among children in São Paulo city. Cross-sectional surveys were conducted in 2010 (baseline) and 2013 (post-PCV10). Healthy PCV-naïve children aged 12–23 months were recruited from primary health centers during immunization campaigns. Nasopharyngeal swabs were collected and tested for Hi; for Spn, all baseline and a stratified random sam ple of 400 post-PCV10 swabs were tested. We compared vaccine-type Spn and NTHi carriage prevalence pre-/post-PCV10, and used logistic regression to estimate PCV10 effectiveness (1-adjusted odds ratio 100%). Overall 501 children were included in the baseline and 1167 in the post-PCV10 survey (including 400 tested for Spn). Spn was detected in 40.3% of children at baseline and 48.8% post PCV10; PCV10 serotypes were found in 19.8% and 1.8% respectively, representing a decline of 90.9% (p < 0.0001). Carriage of vaccine-related serotypes increased (10.8–21.0%, p < 0.0001), driven primarily by a rise in serotype 6C (1.8–11.2%, p < 0.0001); carriage of serotypes 6A and 19A did not significantly change. PCV10 effectiveness (4 doses) against vaccine-type carriage was 97.3% (95% confidence interval 88.7–99.3). NTHi prevalence increased from 26.0% (130/501) to 43.6% (509/1167, p < 0.0001); PCV10 vac cination seemed significantly associated with NTHi carriage, even after adjusting for other known risk factors. Carriage with PCV10 serotypes among toddlers declined dramatically following PCV10 introduc tion in São Paulo, Brazil. No protection of PCV10 against NTHi was observed. Our findings contribute to a growing body of evidence of PCV10 impact on vaccine-type carriage and highlight the importance of PCV10 as a tool to reduce the burden of pneumococcal disease in Brazil and globally.
Timeliness and risk factors associated with delay for pneumococcal conjugate 10-valent routine immunization in Brazilian children
(2017) Sartori, Ana Lucia; Minamisava, Ruth; Afonso, Eliane Terezinha; Policena, Gabriela Moreira; Pessoni, Grécia Carolina; Bierrenbach, Ana Luiza de Souza; Andrade, Ana Lúcia Sampaio Sgambatti de
Background: Vaccination coverage is the usual metrics to evaluate the immunization programs perfor mance. For the 10-valent pneumococcal conjugate (PCV10) vaccine, measuring the delay of vaccination is also important, particularly as younger children are at increased risk of disease. Routinely collected administrative data was used to assess the timeliness of PCV10 vaccination, and the factors associated with delay to receive the first and second doses, and the completion of the PCV10 3 + 1 schedule. Methods: A population-based retrospective cohort study was conducted with children born in 2012 in Central Brazil. Children who received the PCV10 first dose in public health services were followed-up until 23 months of age. Timeliness of receiving each PCV10 dose at any given age was defined as receiving the dose within 28 days grace period from the recommended age by the National Immunization Program. Log-binomial regression models were used to examine risk factors for delays of the first dose and the completion PCV10 3 + 1 schedule. Results: In total, 14,282 children were included in the cohort of study. Delayed vaccination occurred in 9.4%, 23.8%, 36.8% and 39.9% children for the first, second, third and the booster doses, respectively. A total of 1912 children (12.8% of the cohort) were not adequately vaccinated at the 6 months of life; 1,071 (7%) received the second dose after 6 months of age, 784 (5.4%) did not receive the second dose, and 57 (0.4%) received the first dose after six months of life. Conclusion: A considerable delay was found in PCV10 third and booster doses. Almost 2 thousand chil dren had not received the recommended PCV10 doses at 6 months of age. Timeliness of vaccination is an issue in Brazil although high vaccination coverages.
Distribution of invasive Streptococcus pneumoniae serotypes before and 5 years after the introduction of 10-valent pneumococcal conjugate vaccine in Brazil
(2018) Brandileone, Maria Cristina de Cunto; Almeida, Samanta Cristine Grassi; Andrade, Ana Lúcia Sampaio Sgambatti de
Background: In March 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine immunization program in Brazil. We describe the pneumococcal serotypes that caused inva sive pneumococcal diseases (IPD) before and after the introduction of PCV10 using data from a national laboratory-based surveillance system. Method: We compared the prevalence of vaccine types (VT) and non-vaccine types (NVT) of Streptococcus pneumoniae in three periods, pre-PCV10 (January/2005-December/2009), early post-PCV10 (January/2010-December/2013), and late post-PCV10 (January/2014-December/2015), by episode in meningitis and non-meningitis cases and by age group. Changes in serotype prevalence in the early and late post-PCV10 periods were determined using pre-PCV10 period as a reference. Results: A total of 8971 IPD isolates from patients aged 2 months to 99 years were analyzed. In the late post PCV10 period, the VT-IPD reduction in the 2-month to 4-year age group was 83.4% for meningitis and 87.4% for non-meningitis cases; in the age groups 5–17 years, 18–64 years, and 65 years, VT declined by 56.1%, 54.1%, and 47.4%, respectively, in meningitis cases, and by 60.9%, 47.7%, and 53.4%, respectively, in non meningitis cases. NVT-IPD increased throughout the study period, driven mainly by serotypes 3, 6C, and 19A, which remained the predominant types causing IPD in the late post-PCV10 period. Conclusion: We observed direct and indirect PCV10 protection against IPD caused by VT and a shift in the distribution of serotypes 5 years after the introduction of PCV10. Continued IPD surveillance is needed to evaluate the sustainability of the high prevalence of serotypes 3, 6C, and 19A, which were not included in PCV10.
Nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in a Brazilian elderly cohort
(2019) Ramos, Rosemeire Cobo Zanella; Brandileone, Maria Cristina de Cunto; Almeida, Samanta Cristine Grassi; Lemos, Ana Paula Silva de; Sacchi, Claudio Tavares; Gonçalves, Claudia Regina; Gonçalves, Maria Gisele; Fukasawa, Lucila Okuyama; Saraiva, Marcos Daniel Cabral; Rangel, Luis Fernando; Andrade, Ana Lúcia Sampaio Sgambatti de
We aimed to investigate the nasopharyngeal colonization (NPC) by Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in the elderly population and to assess the demographic factors associated with NPC. This was an observational cohort study in which outpatients aged ≥60 years were enrolled from April to August 2017, with a follow-up visit from September through December 2017. Nasopharyngeal (NP) swabs were collected, bacteria were detected and isolated, and isolates were subjected to phenotypic and molecular characterization using standard microbiological techniques. At enrolment, the rates of S. aureus, methicillin-resistant S. aureus (MRSA), H. influenzae, and S. pneumoniae among 776 elderly outpatients were 15.9%, 2.3%, 2.5%, and 2.2%, respectively. Toxin production was detected in 21.1% of methicillin-susceptible S. aureus, and three SCCmec types were identified: II/IIb, IVa, and VI. At the follow-up visit, all carriage rates were similar (p > 0.05) to the rates at enrolment. Most of S. pneumoniae serotypes were not included in pneumococcal conjugate vaccines (PCVs), except for 7F, 3, and 19A. All strains of H. influenzae were non-typeable. Previous use of antibiotics and 23-valent pneumococcal polysaccharide vaccination (p < 0.05) were risk factors for S. aureus and MRSA carriage; S. aureus colonization was also associated with chronic kidney disease (p = 0.021). S. pneumoniae carriage was associated with male gender (p = 0.032) and an absence of diabetes (p = 0.034), while not receiving an influenza vaccine (p = 0.049) and chronic obstructive pulmonary disease (p = 0.031) were risk factors for H. influenzae colonization. The frailty of study participants was not associated with colonization status. We found a higher S. aureus carriage rate compared with the S. pneumoniae- and H. influenzae-carriage rates in a well-attended population in a geriatric outpatient clinic. This is one of the few studies conducted in Brazil that can support future colonization studies among elderly individuals.
Long-term effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae in children in Brazil
(2019) Brandileone, Maria Cristina de Cunto; Ramos, Rosemeire Cobo Zanella; Almeida, Samanta Cristine Grassi; Cassiolato, Ana Paula; Salgado, Maristela Marques; Higa, Fábio Takenori; Minamisava, Ruth; Andrade, Ana Lúcia Sampaio Sgambatti de
program (NIP) in March 2010. In 2017, we investigated the effects of PCV10 on nasopharyngeal carriage of vaccine-types (VT) and non-vaccine-types (NVT) of Streptococcus pneumoniae (Spn) among children liv ing in São Paulo city. We also compared the prevalence of VT and NVT with previous carriage surveys per formed in 2010 (baseline) and 2013. Method: The carriage survey was conducted among 531 children, aged 12 months to <24 months, recruited from public Primary Health Units during the immunization campaign, using previous surveys methodology, except for qPCR, which was performed in the 2017 survey only. Results: No statistical difference was found in the prevalence of Spn either by culture (59.7%) or by qPCR (61.2%). Spn carriage increased from 40.3% (baseline) to 59.7% (2017 survey) (p < 0.001). Colonization by VT isolates significantly decreased by 90.9% (19.8–1.8%) and 95.5% (19.8–0.9%) in the 2013 and 2017 surveys, respectively, compared to that at baseline. NVT isolates increased significantly by 128% (19.6–44.8%) and 185% (19.6–55.9%) in the respective post-PCV10 surveys, most led to high prevalence of serotypes 6C (27%), 15B (9.8%), 19A (9.2%), 15A (6.0%), and 16F (5.7%). In 2017, reduction in serotype 6A (4.2–0.6%, p < 0.001) and increase in serotype 19A (1.8–6.0%, p = 0.001) were found; serotype 3 isolate was not detected in the present survey. We identified the emergence of 19A isolates CC320, associated with high penicillin (MIC 2.0 mg/L) and cefotaxime (MIC 1.0 mg/L) values. Conclusion: After 7 years of PCV10 introduction in the NIP, colonization by VT among toddlers decreased substantially to a residual level, along with substantial serotype replacement by novel serotypes not present in any current conjugated pneumococcal vaccine and serotype 19A. The present findings can assist policy decisions in Brazil.
Course of serological tests in treated subjects with chronic Trypanosoma cruzi infection: a systematic review and meta-analysis of individual participant data
(2018) Sguassero, Yanina; Roberts, Karen N.; Harvey, Guillermina B.; Comandé, Daniel; Ciapponi, Agustín; Cuesta, Cristina B.; Aguiar, Camila; Castro, Ana Maria de; Danesi, Emmaría; Andrade , Ana Lúcia Sampaio Sgambatti de
Objective: To determine the course of serological tests in subjects with chronic Trypanosoma cruzi infection treated with anti-trypanosomal drugs. Methods: A systematic review and meta-analysis was conducted using individual participant data. Survival analysis and the Cox proportional hazards regression model with random effects to adjust for covariates were applied. The protocol was registered in the PROSPERO database (http://www.crd.york.ac. uk/PROSPERO; CRD42012002162). Results: A total of 27 studies (1296 subjects) conducted in eight countries were included. The risk of bias was low for all domains in 17 studies (63.0%). Nine hundred and thirteen subjects were assessed (149 seroreversion events, 83.7% censored data) for enzyme-linked immunosorbent assay (ELISA), 670 subjects (134 events, 80.0% censored) for indirect immunofluorescence assay (IIF), and 548 subjects (99 events, 82.0% censored) for indirect hemagglutination assay (IHA). A higher probability of seroreversion was observed within a shorter time span in subjects aged 1–19 years compared to adults. The chance of seroreversion also varied according to the country where the infection might have been acquired. For instance, the pooled adjusted hazard ratio between children/adolescents and adults for the IIF test was 1.54 (95% confidence interval 0.64–3.71) for certain countries of South America (Argentina, Bolivia, Chile, and Paraguay) and 9.37 (95% confidence interval 3.44–25.50) for Brazil. Conclusions: The disappearance of anti-T. cruzi antibodies was demonstrated along the course of follow up. An interaction between age at treatment and country setting was found. © 2018 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases
Single-dose varicella vaccine effectiveness in Brazil: a case-control study
(2018) Andrade, Ana Lúcia Sampaio Sgambatti de; Vieira, Maria Aparecida da Silva; Minamisava, Ruth; Toscano, Cristiana Maria; Souza, Menira Borges de Lima Dias e; Fiaccadori, Fabíola Souza; Figueiredo, Cristina Adelaide; Curti, Suely Pires; Nerger, Maria Ligia Bacciotte Ramos; Bierrenbach, Ana Luiza de Souza
Background: Varicella vaccine was introduced into the Brazilian Immunization Program in October 2013, as a single-dose schedule administered at 15 months of age. Its effectiveness had not yet been assessed in the country. Methods: A matched case-control study was carried out in São Paulo and Goiânia (Southeast and Midwest regions, respectively), Brazil. Suspected cases, were identified through a prospective surveillance estab lished in the study sites. All cases had specimens from skin lesion collected for molecular laboratory test ing. Cases were confirmed by either clinical or PCR of skin lesions and classified as mild, moderate, and severe disease. Methods: Two neighborhood controls were selected for each case. Cases and controls were aged 15–32 months and interviewed at home. Evidence of prior vaccination was obtained from vaccination cards. Univariate and multivariate logistic regression models were used, and odds ratio and its respective 95% confidence intervals were estimated. Vaccine effectiveness was estimated by comparing de odds of having received varicella vaccine among cases and controls. Results: A total of 168 cases and 301 controls were enrolled. Moderate and severe illness, was found in 33.3% and 9.9% of the cases. Effectiveness of a single dose varicella vaccine was 86% (95%CI 72–92%) against disease of any severity and 93% (95%CI 82–97%) against moderate and severe disease. Out of 168 cases, 81.8% had positive PCR results for wild-type strains, and 22.0% were breakthrough varicella cases. Breakthrough cases were milder compared to non-breakthrough cases (p < .001). Conclusions: Effectiveness of single dose varicella vaccine in Brazil is comparable to that in other coun tries where breakthrough varicella cases have also been found to occur. The goal of the varicella vaccina tion program, along with disease burden and affordability should be taken into consideration when considering the adoption of a second dose of varicella vaccine into national immunization programs. 2017 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Impact of meningococcal C conjugate vaccination four years after introduction of routine childhood immunization in Brazil
(2017) Andrade, Ana Lúcia Sampaio Sgambatti de; Minamisava, Ruth; Tomich, Lísia Gomes Martins de Moura; Lemos, Ana Paula Silva de; Gorla, Maria Cecilia Outeiro; Brandileone, Maria Cristina de Cunto; Domingues, Carla Magda Allan Santos; Moraes, Camile de; Policena, Gabriela Moreira; Bierrenbach, Ana Luiza de Souza
Background: Routine infant immunization with meningococcal C conjugate (MCC) vaccination started in Brazil in November 2010, scheduled at three and five months plus a booster at 12–15 months of age. No catch-up was implemented. We assessed the impact of vaccination on meningococcal C disease (MenC) four years after vaccination start in the National Immunization Program. Methods: We performed an ecological quasi-experimental design from 2008 to 2014 using a determinis tic linkage between the National Notification and the National Reference Laboratory databases for menin gitis. We conducted an interrupted time-series analysis considering Brazil except for Salvador municipality, because an epidemic of serogroup C disease occurred in this city, which prompted a mass vaccination campaign with catch-up for adolescents in 2010. Observed MenC rates in the post vaccination period were compared to expected rates calculated from the pre-vaccination years. Results for Salvador were presented as descriptive data. An additional time-series analysis was performed for the state of São Paulo. Results: A total of 18,136 MenC cases were analyzed. The highest incidence rates were observed for infants aged <12 months and no second incident peak was observed for adolescents. For Brazil, MenC rates were reduced by 67.2% (95%CI 43.0–91.4%) for infants <12 months of age, 92.0% (77.3–106.8%) for the age-group 12–23 months, and 64.6% (24.6–104.5%) for children aged 2–4 years. For children 5– 9 years old, MenC rates reduced 19.2% (9.5–28.9%). Overall, 955 MenC cases were averted in Brazil in individuals aged <40 years after MCC vaccination. Results from São Paulo State, mirror the patterns seen in Brazil. Conclusion: After four years of infants and toddlers vaccination start, MenC invasive disease reduced in the target population. This investigation provide a robust baseline to ascertain how much the upcoming catch-up dose in 12–13 years of age will accelerate the decrease in MenC incidence rates among youths in Brazil.
Genomic surveillance of Neisseria meningitidis serogroup B invasive strains: diversity of vaccine antigen types, Brazil, 2016-2018
(2020) Lemos, Ana Paula Silva de; Sacchi, Claudio Tavares; Gonçalves, Claudia Regina; Camargo, Carlos Henrique; Andrade, Ana Lúcia Sampaio Sgambatti de
Background Neisseria meningitidis serogroup B remains a prominent cause of invasive meningococcal disease (IMD) in Brazil. Because two novel protein-based vaccines against serogroup B are available, the main purpose of this study was to provide data on the diversity and distribution of meningococcal vaccine antigen types circulating in Brazil. Methodology Genetic lineages, vaccine antigen types, and allele types of antimicrobial-associated resistance genes based on whole-genome sequencing of a collection of 145 Neisseria meningitidis serogroup B invasive strains recovered in Brazil from 2016 to 2018 were collected. Results A total of 11 clonal complexes (ccs) were identified among the 145 isolates, four of which were predominant, namely, cc461, cc35, cc32, and cc213, accounting for 72.0% of isolates. The most prevalent fHbp peptides were 24 (subfamily A/variant 2), 47 (subfamily A/variant 3), 1 (subfamily B/variant 1) and 45 (subfamily A/variant 3), which were predominantly associated with cc35, cc461, cc32, and cc213, respectively. The NadA peptide was detected in only 26.2% of the isolates. The most frequent NadA peptide 1 was found almost exclusively in cc32. We found seven NHBA peptides that accounted for 74.5% of isolates, and the newly described peptide 1390 was the most prevalent peptide exclusively associated with cc461. Mutated penA alleles were detected in 56.5% of the isolates, whereas no rpoB and gyrA mutant alleles were found. Conclusion During the study period, changes in the clonal structure of circulating strains were observed, without a predominance of a single hyperinvasive lineage, indicating that an epidemiologic shift has occurred that led to a diversity of vaccine antigen types in recent years in Brazil.
Effectiveness of pneumococcal vaccine on otitis media in children: a systematic review
(2022) Marra, Lays Pires; Sartori, Ana Lucia; Silveira, Martha Silvia Martinez; Toscano, Cristiana Maria; Andrade, Ana Lúcia Sampaio Sgambatti de
Objectives: We aimed to determine the effectiveness of pneumococcal vaccines on otitis media (OM) and acute otitis media (AOM) in children. Methods: We conducted a systematic search in databases PubMed (MEDLINE), Embase, Lilacs, and Web of Science. We included observational studies that evaluated any pneumococcal vaccine – including 7, 10, and 13-valent pneumococcal conjugate vaccines (PCV7, PCV10, and PCV13) and 23-valent polysaccharide vaccines (PPSV23) as the intervention, in children aged less than five years. Results: Out of the 2112 screened studies, 48 observational studies complied with the eligibility criteria and therefore were included in this review. Of the included studies, 30 (63%) were before-after, eleven (23%) cohort, six (13%) time series, and one (2%) case-control study designs. Vaccine effectiveness (VE) in preventing OM or AOM varied by vaccine type. In children under 24 months VE ranged from 8% and 42.7% (PCV7), 5.6% to 84% (PCV10) and 2.2% to 68% (PCV13). In children aged less than 60 months, VE ranged between 13.2% and 39% for PCV7, 11% to 39% for PCV10 (only children under 48 months), and 39% to 41% (PCV13). Conclusions: Our results demonstrate significant effect of pneumococcal vaccination in decreasing OM or AOM in children under five years old in several countries supporting the public health value of introducing PCVs in national immunization programs.
Cost-effectiveness of maternal pertussis immunization: implications of a dynamic transmission model for low- and middle-income countries
(2021) Sun-Young, Kim; Kyung-Duk, Min; Russell, Louise B.; Toscano, Cristiana Maria; Minamisava, Ruth; Andrade, Ana Lúcia Sampaio Sgambatti de; Sanderson, Colin; Sinha, Anushua
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%.

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