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Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease has been subjected to laboratory-based surveillance in Latin American and Caribbean countries since 1993. Invasive pneumococcal diseases remain a major cause of death and disability worldwide, particularly in children. We therefore aimed to assess the direct effect of pneumococcal conjugate vaccines (PCVs) on the distribution of pneumococcal serotypes causing invasive pneumococcal disease in children younger than 5 years before and after PCV introduction.We did a multicentre, retrospective observational study in eight countries that had introduced PCV (ie, PCV countries) in the Latin American and Caribbean region: Argentina, Brazil, Chile, Colombia, Dominican Republic, Mexico, Paraguay, and Uruguay. Cuba and Venezuela were also included as non-PCV countries. Isolate data for Streptococcus pneumoniae were obtained between 2006 and 2017 from children younger than 5 years with an invasive pneumococcal disease from local laboratories or hospitals. Species' confirmation and capsular serotyping were done by the respective national reference laboratories. Databases from the Sistema Regional de Vacunas (SIREVA) participating countries were managed and cleaned in a unified database using Microsoft Excel 2016 and the program R (version 3.6.1). Analysis involved percentage change in vaccine serotypes between pre-PCV and post-PCV periods and the annual reporting rate of invasive pneumococcal diseases per 100 000 children younger than 5 years, which was used as a population reference to calculate percentage vaccine type reduction.Between 2006 and 2017, 12 269 isolates of invasive pneumococcal disease were collected from children younger than 5 years in the ten Latin American and Caribbean countries. The ten serotypes included in ten-valent pneumococcal conjugate vaccine (PCV10) decreased significantly (p0·0001) after any PCV introduction, except for the Dominican Republic. The percentage change for the ten vaccine serotypes in PCV10 countries was -91·6% in Brazil (530 [72·9%] of 727 before, 27 [6·1%] of 441 after); -85·0% in Chile (613 [72·6%] of 844 before, 44 [10·9%] of 404] after); -84·7% in Colombia (231 [63·1%] of 366 before, 34 [9·7%] of 352 after); and -73·8% in Paraguay (127 [77·0%] of 165 before, 22 [20·2%] of 109 after). In the 13-valent pneumococcal conjugate vaccine (PCV13) countries, the percentage change for the 13 vaccine serotypes was -59·6% in Argentina (853 [85·0%] of 1003 before, 149 [34·3%] of 434 after); -16·5% in the Dominican Republic (95 [80·5%] of 118 before, 39 [67·2%] of 58 after); -43·7% in Mexico (202 [73·2%] of 276 before, 63 [41·2%] of 153 after); and -45·9% in Uruguay (138 [80·7%] of 171 before, 38 [43·7%] of 87 after). Annual reporting rates showed a reduction from -82·5% (6·21 before vs 1·09 after per 100 000, 95% CI -61·6 to -92·0) to -94·7% (1·15 vs 0·06 per 100 000, -89·7 to -97·3) for PCV10 countries, and -58·8% (2·98 vs 1·23 per 100 000, -21·4 to -78·4) to -82·9% (7·80 vs 1·33 per 100 000, -76·9 to -87·4) for PCV13 countries. An increase in the amount of non-vaccine types was observed in the eight countries after PCV introduction together with an increase in their percentage in relation to total invasive strains in the post-PCV period.SIREVA laboratory surveillance was able to confirm the effect of PCV vaccine on serotypes causing invasive pneumococcal disease in the eight PCV countries. Improved monitoring of the effect and trends in vaccine type as well as in non-vaccine type isolates is needed, as this information will be relevant for future decisions associated with new PCVs.None.For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

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: Sao Paulo, Parana 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.

Background: In Latin America, few studies have been carried out on methicillin-resistant Staphylococcus aureus carriage in the pediatric population. We conducted a survey of nasal S. aureus carriage in neonates and in children attending the pediatric outpatient clinics in a large Brazilian city with high antimicrobial consumption. Methods: Pernasal swabs of neonates were collected upon admission and at discharge in four neonatal intensive care units and of children less than five years of age during outpatient visits. Methicillin-resistant S. aureus isolates were characterized for antibiotic susceptibility, mec gene presence, pulsed-field gel electrophoresis, spa type, SCCmec-type, multilocus sequence type, and presence of Panton-Valentine leukocidin genes. Results: S. aureus was carried by 9.1% and 20.1% of the 701 neonates and of 2034 children attending the outpatient clinics, respectively; methicillin-resistant S. aureus carriage was detected in 0.6% and 0.2%, of the these populations, respectively. Healthcare-associated methicillin-resistant S. aureus strains found in neonates from neonatal intensive care units and outpatients were genetically related to the Brazilian (SCCmec-III, ST239) and to the Pediatric (SCCmec-IV, ST5) clones. Community-associated methicillin-resistant S. aureus was only detected in outpatients. None of the methicillin-resistant S. aureus strains contained the Panton-Valentine leukocidin gene. Methicillin-resistant S. aureus strains related to the Brazilian clone showed multidrug resistance pattern. Conclusions: Despite the high antibiotic pressure in our area, and the cross transmission of the healthcare-associated methicillin-resistant S. aureus clones between neonatal intensive care units and outpatients, the prevalence of methicillin-resistant S. aureus carriage is still low in our setting. Keywords: Staphylococcus aureus carriage, Methicillin-resistant Staphylococcus aureus, Neonates, Children

Tenofovir disoproxil fumarate (TDF) is a first-line drug used in patients with highly active retroviral disease; however, it can cause renal failure associated with many tubular anomalies that may be due to down regulation of a variety of ion transporters. Because rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist induces the expression of many of these same transporters, we tested if the nephrotoxicity can be ameliorated by its use. High doses of TDF caused severe renal failure in rats accompanied by a reduction in endothelial nitric-oxide synthase and intense renal vasoconstriction; all of which were significantly improved by rosiglitazone treatment. Low-dose TDF did not alter glomerular filtration rate but produced significant phosphaturia, proximal tubular acidosis, polyuria and a reduced urinary concentrating ability. These alterations were caused by specific downregulation of the sodium-phosphorus cotransporter, sodium/hydrogen exchanger 3 and aquaporin 2. A Fanconi's-like syndrome was ruled out as there was no proteinuria or glycosuria. Rosiglitazone reversed TDF-induced tubular nephrotoxicity, normalized urinary biochemical parameters and membrane transporter protein expression. These studies suggest that rosiglitazone treatment might be useful in patients presenting with TFV-induced nephrotoxicity especially in those with hypophosphatemia or reduced glomerular filtration rate.

Pneumococcal protein vaccine based on pneumococcal surface protein A (PspA) is in development with the potential to offer broad range of protection against different strains. We have investigated the frequency of PspA family 1 (Fam1) and family 2 (Fam2) proteins among Streptococcus pneumoniae recovered from ongoing surveillance in Brazil. Fam1 and Fam2 were expressed in comparable rates among 366 isolates, with the potential coverage of 94.3%. PspA families were not associated to age group or source of isolates. However, considering the significant tendency of increasing prevalence of Fam2 associated to widespread dissemination of the genetically-related resistant strains, the monitoring of the PspA families derived from population-based data may be necessary in the context of vaccine development.

Positive effect of the induction of p21 WAF1/CIP1 on the course of ischemic acute renal failure. Background The p21 protein is found in the nucleus of most cells where it modulates cell cycle activity. At low levels, p21 stabilizes interactions between D cyclins and their cyclin-dependent kinases (cdks), but at high levels after induction by several different stress pathways, it causes cell cycle arrest. The p21 mRNA is induced in murine kidney after several types of acute renal failure, including cisplatin administration, ischemia-reperfusion, and ureteral obstruction. We reported that after cisplatin injection, mice with a p21 gene deletion developed much more severe renal damage than wild-type mice. To dissociate the effects of cisplatin-induced DNA damage and subsequent initiation of DNA damage-dependent cell death pathways from effects of acute renal failure, we have now examined mice after ischemia-reperfusion, a model of renal failure not associated with genotoxin-induced DNA damage early after the injury. Methods Wild-type and p21(-/-) mice were made ischemic by clamping both renal hila for 30 or 50 minutes. At various times after reflow, mortality and parameters of renal function and morphology were quantified. Also, the nuclear proteins p21 and proliferating cell nuclear antigen (PCNA) were localized in kidney sections by immunohistochemistry. Results Kidney function was more impaired and mortality increased significantly in p21(-/-) mice as compared with p21(+/+) mice. We found more cell cycle activity, indicated by increased number of mitotic cells and nuclear PCNA-positive cells, in kidney of p21(-/-) mice. Conclusions In this study, p21(-/-) mice were more susceptible to ischemia-induced acute renal failure, with similarly elevated levels of parameters of cell cycle activity. We propose that the increased and inappropriate cell cycle activity in kidney cells is responsible for the increased kidney impairment and mortality.