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Arenas C.J.V.,University of Sao Paulo | Botelho A.C.,Laboratory of Pediatric Infectious Diseases | Passos S.D.,Laboratory of Pediatric Infectious Diseases | Zanotto P.M.A.,University of Sao Paulo
Revista da Associacao Medica Brasileira | Year: 2012

Objective: To study the antibody prevalence against dengue in the municipality of Jundiaí, São Paulo, Brazil, due to the low number of official confirmed autochthonous cases. Methods: A serological study on dengue infection was conducted during January 2010 and previous reports on dengue and entomological surveillance during that period were reviewed. Results: A prevalence of 7.8% IgG positive (68:876) was found. Furthermore, based on the detection of IgM antibodies in five samples, it was observed that the incidence of dengue in the city at the time of the survey contrasts with the absence of notifications by local health authorities over the same period of time. Conclusion: These results highlight the discrepancies between the actual and the detected number of dengue infections, possibly due to significant numbers of asymptomatic infections aggravated by difficulties with dengue clinical diagnosis. © 2012 Elsevier Editiora Ltda. All right reserved.

Van Der Maten E.,Laboratory of Pediatric Infectious Diseases | Van Selm S.,Laboratory of Pediatric Infectious Diseases | Langereis J.D.,Laboratory of Pediatric Infectious Diseases | Bootsma H.J.,Laboratory of Pediatric Infectious Diseases | And 7 more authors.
Journal of Infectious Diseases | Year: 2016

Streptococcus pneumoniae is a major cause of life-threatening infections. Complement activation plays a vital role in opsonophagocytic killing of pneumococci in blood. Initial complement activation via the classical and lectin pathways is amplified through the alternative pathway amplification loop. Alternative pathway activity is inhibited by complement factor H (FH). Our study demonstrates the functional consequences of the variability in human serum FH levels on host defense. Using an in vivo mouse model combined with human in vitro assays, we show that the level of serum FH correlates with the efficacy of opsonophagocytic killing of pneumococci. In summary, we found that FH levels determine a delicate balance of alternative pathway activity, thus affecting the resistance to invasive pneumococcal disease. Our results suggest that variation in FH expression levels, naturally occurring in the human population, plays a thus far unrecognized role in the resistance to invasive pneumococcal disease. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Cremers A.J.H.,Laboratory of Pediatric Infectious Diseases | Lut J.,Laboratory of Pediatric Infectious Diseases | Hermans P.W.M.,Laboratory of Pediatric Infectious Diseases | Hermans P.W.M.,Crucell | And 3 more authors.
Clinical and Vaccine Immunology | Year: 2014

The incidence of invasive pneumococcal disease (IPD) rises with age. Among adult IPD patients, the avidity of antipneumococcal polysaccharide antibodies against the infecting serotype increased with age and severity of disease, indicating that susceptibility to IPD in the elderly may rather be due to flaws in other aspects of opsonophagocytosis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Cremers A.J.H.,Laboratory of Pediatric Infectious Diseases | Zomer A.L.,Laboratory of Pediatric Infectious Diseases | Zomer A.L.,Center for Molecular and Biomolecular Informatics Bacterial Genomics | Ferwerda G.,Laboratory of Pediatric Infectious Diseases | And 10 more authors.
Microbiome | Year: 2014

Background: Several cohort studies have indicated associations between S. pneumoniae and other microbes in the nasopharynx. To study causal relationships between the nasopharyngeal microbiome and pneumococcal carriage, we employed an experimental human pneumococcal carriage model. Healthy adult volunteers were assessed for pneumococcal carriage by culture of nasal wash samples (NWS). Those without natural pneumococcal carriage received an intranasal pneumococcal inoculation with serotype 6B or 23F. The composition of the nasopharyngeal microbiome was longitudinally studied by 16S rDNA pyrosequencing on NWS collected before and after challenge.Results: Among 40 selected volunteers, 10 were natural carriers and 30 were experimentally challenged. At baseline, five distinct nasopharyngeal microbiome profiles were identified. The phylogenetic distance between microbiomes of natural pneumococcal carriers was particularly large compared to non-carriers. A more diverse microbiome prior to inoculation was associated with the establishment of pneumococcal carriage. Perturbation of microbiome diversity upon pneumococcal challenge was strain specific. Shifts in microbiome profile occurred after pneumococcal exposure, and those volunteers who acquired carriage more often diverted from their original profile. S. pneumoniae was little prominent in the microbiome of pneumococcal carriers.Conclusion: Pneumococcal acquisition in healthy adults is more likely to occur in a diverse microbiome and appears to promote microbial heterogeneity. © 2014 Cremers et al.

Cremers A.J.H.,Laboratory of Pediatric Infectious Diseases | Hagen F.,Canisius Wilhelmina Hospital | Hermans P.W.M.,Laboratory of Pediatric Infectious Diseases | Hermans P.W.M.,Crucell | And 2 more authors.
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2014

Detection of pneumococcal DNA in blood could be a fast alternative for blood culture in invasive pneumococcal disease (IPD). In this study we compared the diagnostic value of the serum pneumococcal DNA load between different clinical syndromes in adults with bacteremic pneumococcal infections, also after initiation of antibiotic treatment. Adults hospitalized with a blood culture proven pneumococcal infection between December 2008 and June 2013 were retrospectively included. Pneumococcal DNA loads in corresponding serum samples were determined by qPCR. Data on clinical diagnosis, course of disease and antibiotic treatment were extracted from medical records. For 53 IPD cases eligible stored serum samples were retrieved. The proportion of samples positive in qPCR was lower in uncomplicated pneumonia compared with other clinical syndromes (59.5 % vs. 100 %, p=0.005). The pneumococcal DNA load was higher in cases other than uncomplicated pneumonia (p=0.043) as well as in more severe disease (p-values 0.018, 0.029 and 0.003 for PSI Risk Class IV/V, ICU admission and mortality, respectively). Both detection of pneumococcal DNA and distribution of load did not significantly change over the first days of hospitalization despite treatment with appropriate antibiotics. Detection of pneumococcal DNA in serum was more sensitive in clinical syndromes other than uncomplicated pneumonia. Furthermore, the pneumococcal DNA load was associated with the type of IPD and severity of disease. Since the serum pneumococcal DNA load seemed unaffected by antibiotic treatment during the first days of IPD, it may offer an alternative for culture methods after prior antibiotic use. © 2014 Springer-Verlag.

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