Serotype distribution of remaining pneumococcal meningitis in the mature PCV10/13 period: Findings from the PSERENADE Project

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed

Global landscape review of serotype-specific invasive pneumococcal disease surveillance among countries using PCV10/13: The pneumococcal serotype replacement and distribution estimation (PSERENADE) project

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon

Incorporation of Real-Time PCR into Routine Public Health Surveillance of Culture Negative Bacterial Meningitis in Sao Paulo, Brazil

Real-time (RT)-PCR increases diagnostic yield for bacterial meningitis and is ideal for incorporation into routine surveillance in a developing country. We validated a multiplex RT-PCR assay for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae in Brazil. Risk factors for being culture-negative, RT-PCR positive were determined. The sensitivity of RT-PCR in cerebrospinal fluid (CSF) was 100% (95% confidence limits, 96.0%-100%) for N. meningitidis, 97.8% (85.5%-99.9%) for S. pneumoniae, and 66.7% (9.4%-99.2%) for H. influenzae. Specificity ranged from 98.9% to 100%. Addition of RT-PCR to routine microbiologic methods increased the yield for detection of S. pneumoniae, N. meningitidis, and H. influenzae cases by 52%, 85%, and 20%, respectively. The main risk factor for being culture negative and RT-PCR positive was presence of antibiotic in CSF (odds ratio 12.2, 95% CI 5.9-25.0). RT-PCR using CSF was highly sensitive and specific and substantially added to measures of meningitis disease burden when incorporated into routine public health surveillance in Brazil.Secretary of Health of Sao Paulo State, BrazilBrazilian Council for Science and Technology Development (CNPq)[301340/2007-2]National Institute of Allergy and Infectious Diseases[K24 AI52788]National Institutes of Health (NIH)[D43TW006592

Sensibilidade a antimicrobianos de bactérias isoladas do trato respiratório de pacientes com infecções respiratórias adquiridas na comunidade: resultados brasileiros do Programa SENTRY de Vigilância de Resistência a Antimicrobianos dos anos de 1997 e 1998 Susceptibility to respiratory tract isolated bacteria to antimicrobial agents in patients with community-acquired respiratory tract infections: 1997 and 1998 Brazilian data of the SENTRY surveillance program of resistance to antimicrobial agents

O tratamento da pneumonia adquirida na comunidade (PAC) é habitualmente empírico e o uso de antimicrobianos é baseado em estudos de vigilância. O programa SENTRY foi desenhado para monitorar a resistência a antimicrobianos através de uma rede internacional de laboratórios. Três centros no Brasil participaram do Programa SENTRY em 1997 e em 1998. Métodos: Um total de 344 isolados bacterianos coletados de pacientes com PAC em 1997 e 1998 foram testados contra mais de 20 agentes antimicrobianos pelo método de microdiluição em caldo. Resultados: Entre os S. pneumoniae (176 isolados), 71,6% foram sensíveis à penicilina. Alto nível de resistência à penicilina e resistência à cefotaxima foram encontrados em 2,3 e 4,0%, respectivamente. As novas quinolonas levofloxacina (MIC90, 2mig/mL) e gatifloxacina (MIC90, 0,5mig/mL) foram ativas contra 100% dos isolados testados. Entre os outros antimicrobianos não beta-lactâmicos testados, os mais ativos foram (% de sensibilidade): cloranfenicol (97,5%) > clindamicina (94%) > azitromicina (90,3%) > claritromicina (89,4%) > tetraciclina (76,4%) > sulfametoxazol/trimetoprim (60,2%). A percentagem de Haemophilus influenzae (101 isolados) resistentes à amoxicilina foi de 90,1%, enquanto entre Moraxella catarrhalis (67 isolados) somente 9,0% foram sensíveis. O ácido clavulânico restaurou a atividade de amoxicilina contra H. influenzae e M. catarrhalis. Porém, H. influenzae demonstrou níveis aumentados de resistência para sulfametoxazol/trimetoprim (55,1% de sensibilidade), claritromicina (80,4% de sensibilidade) e cefaclor (88,2% de sensibilidade). Todos os isolados de H. influenzae e M. catarrhalis foram sensíveis à levofloxacina (MIC90, <= 0,5mig/mL para ambos) e gatifloxacina (MIC90, <= 0,06mig/mL para ambos) apresentando MICs muito baixos. Conclusões: Os resultados indicam que a prevalência de S. pneumoniae com alto grau de resistência à penicilina é ainda baixa no Brasil; porém, a prevalência de S. pneumoniae com resistência intermediária à penicilina e resistência cruzada a outras classes de antimicrobianos é relativamente alta em nosso meio. Por outro lado, as novas quinolonas são altamente ativas contra S. pneumoniae e outros patógenos responsáveis por infecções respiratórias adquiridas na comunidade.<br>Background: Antimicrobial treatment of community-acquired respiratory tract infections (CARTI) is usually empiric and antibiotics are chosen on the basis of surveillance studies. The SENTRY Program was designed to monitor antimicrobial resistance via a worldwide surveillance network of sentinel laboratories. Three sites in Brazil participated in the 1997 and 1998 SENTRY Program. Methods: A total of 344 bacterial isolates, collected from patients with CARTI in 1997 and 1998, were tested against more than 20 antimicrobial agents by the broth microdilution method. Results: Among S. pneumoniae (176 isolates), 71.6% were susceptible to penicillin. High level resistance to penicillin and resistance to cefotaxime was found in 2.3 and 4.0%, respectively. The newer quinolones, levofloxacin, (MIC90 of 2 mug/mL) and gatifloxacin (MIC90 of 0.5 mug/mL) were active against 100% of the isolates tested. Among the other non-beta-lactam drugs tested, the rank order of pneumococci activity was (% susceptible): chloramphenicol (97.5%) > clindamycin (94.0%) > azithromycin (90.3%) > clarithromycin (89.4%) > tetracycline (76.4%) > trimethoprim/sulfamethoxazole (60.2%). The percentage of Haemophilus influenzae (101 isolates) susceptible to amoxicillin was 90.1%, whereas among Moraxella catarrhalis (67 isolates) only 9.0% were susceptible. Clavulanic acid restored the activity of amoxicillin against both H. influenzae and M. catarrhalis. However, H. influenzae showed increased levels of resistance to trimethoprim/sulfametoxazole (55.1% susceptibility), clarithromycin (80.4% susceptibility), and cefaclor (88.2%) susceptibility). All H. influenzae and M. catarrhalis isolates were susceptible to levofloxacin (MIC90, < 0.5 mug/mL for both) and gatifloxacin (MIC90, < 0.06 mug/mL for both) with very low MICs. Conclusion: Results indicate that the rate of S. pneumoniae showing high-level penicillin resistance is still low in Brazil. However, intermediate resistance to penicillin associated with resistance to other classes of antimicrobial agents was relatively high. On the other hand, the new quinolones were highly active against 100% of the respiratory pathogens tested