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High levels of naturally occurring IgG antibodies to mucin 1 (MUC1), a membrane-bound glycoprotein that is overexpressed in patients with breast cancer, are associated with good prognosis. This suggests that endogenous anti-MUC1 antibodies have a protective effect and, through antibody-mediated host immunosurveillance mechanisms, might contribute to a cancer-free state. To test this possibility, we characterized a large number of multiethnic patients with breast cancer and matched controls for IgG antibodies to MUC1. We also aimed to determine whether the magnitude of anti-MUC1 antibody responsiveness was associated with particular immunoglobulin GM (γ marker), KM (κ marker), and Fcγ receptors (FcγR) genotypes. After adjusting for the confounding variables in a multivariate analysis, we found no significant difference in the levels of anti-MUC1 IgG antibodies between patients and cancer-free controls. However, in patients and controls, particular GM, KM, and FcγR genotypes-individually or epistatically-were significantly associated with the levels of anti-MUC1 IgG antibodies in a racially restricted manner. These findings, if confirmed in an independent investigation, could help identify individuals most likely to benefit from a MUC1-based therapeutic or prophylactic vaccine for MUC1-overexpressing malignancies., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Biotinidase deficiency is an inherited metabolic disorder characterized by neurological and cutaneous symptoms. Fortunately, it can be treated and the symptoms prevented by oral administration of the vitamin biotin. Using dried blood-soaked filter paper cards, biotinidase activity was determined in the sera of 225,136 newborns in Brazil. Mutation analysis performed on DNA from 21 babies with low serum biotinidase activity confirmed that 3 had profound biotinidase deficiency (less than 10% of mean normal sera biotinidase activity), 10 had partial biotinidase deficiency (10 to 30% of mean normal serum activity), 1 was homozygous for partial biotinidase deficiency, 4 were heterozygous for either profound or partial deficiency, and 3 were normal. Variability in serum enzyme activities and discrepancies with mutation analyses were probably due to inappropriate handling and storage of samples sent to the laboratory. Obtaining an appropriate control serum at the same time as that of the suspected child will undoubtedly decrease the false-positive rate (0.09%). Mutation analysis can be used to confirm the genotype of these children. The estimated incidence of biotinidase deficiency in Brazil is about 1 in 9,000, higher than in most other countries. Screening and treatment of biotinidase deficiency are effective and warranted. These results strongly suggest that biotinidase deficiency should be included in the newborn mass screening program of Brazil.

The susceptibility of nasopharyngeal Streptococcus pneumoniae to eight antibiotics was studied in 482 children under 5 years of age with community-acquired pneumonia and in 429 healthy pneumococci carriers in Fortaleza, Brazil. Serotyping of strains with pooled and type-specific antisera was also performed. Overall, S. pneumoniae was isolated from 499/911 (55%) children. The carriage rate in children attending day-care centres was higher (72%) than in children with pneumonia (50%) (P<0.001). MIC determination in 441 strains revealed 45% to be intermediate penicillin-resistant and 4% high penicillin-resistant strains. Resistance rates to co-trimoxazole and erythromycin were 42 and 23%, respectively. Serotyping of 211 penicillin-resistant and 58 randomly selected penicillin-susceptible isolates showed that 78% of the strains belonged to paediatric serogroups 6, 14, 19 and 23 (86% of the penicillin-resistant and 51% of the penicillin-susceptible strains, P=0.001). Resistance rates of S. pneumoniae to penicillin and co-trimoxazole in Fortaleza were higher than previously reported in Brazil and associated with paediatric serogroups 6, 14, 19 and 23.

Background: Gram-negative bacilli are not infrequently encountered as etiologic organisms of pneumonia in children in warm-climate countries., Objectives: To investigate the nasopharyngeal carriage rate and antimicrobial susceptibility patterns of gram-negative bacilli colonizing children with community-acquired pneumonia in Fortaleza, Brazil., Methods: A single nasopharyngeal specimen was collected from children 2 months to 5 years of age presenting at one of the three children's hospitals in Fortaleza and fulfilling the World Health Organization criteria for pneumonia. Randomly recruited healthy children from public daycare centers and immunization clinics served as controls., Results: The study included 912 children, 482 (53%) with pneumonia and 430 (47%) controls. Aerobic gram-negative bacilli were seen in 79 (16%) of the 482 children with pneumonia and 51 (12%) of the 430 healthy controls. Nonfermentative gram-negative bacilli were seen in 85 (18%) of children with pneumonia and 54 (13%) of healthy controls. Neither gender, nutritional status, season, previous hospital admission nor antibiotic use was associated with carriage with gram-negative bacilli. However, pneumonia was associated with increased carriage, whereas concomitant colonization with Streptococcus pneumoniae or Haemophilus influenzae was associated with decreased carriage with gram-negative bacilli. Only 36% of all Escherichia species and 76% of all Klebsiella isolates were susceptible to cotrimoxazole; 90% of all Acinetobacter species were susceptible to gentamicin., Conclusion: Nasopharyngeal carriage with gram-negative bacilli, in particular with Acinetobacter species, is common and associated with a clinical diagnosis of community-acquired pneumonia in children in Fortaleza, Brazil.

To study clonal diversity of penicillin-resistant Streptococcus pneumoniae, 161 randomly selected isolates with reduced susceptibility to penicillin, collected from the nasopharynx of children under 5 years of age with community-acquired pneumonia and healthy controls from public day-care and immunization centres in Fortaleza, Brazil, were characterized by microbiological and serological techniques and automated ribotyping. Also included were 44 randomly selected penicillin-susceptible strains and three international reference strains. With automated ribotyping 75 ribopatterns were observed: 50 ribogroups were unique and 25 ribogroups were represented by two or more isolates. Genetic diversity was extensive but some degree of genetic homogeneity was found in strains from children with pneumonia, strains from children in day-care centres, isolates with reduced susceptibility to penicillin and isolates expressing 'paediatric' serogroups. Fourteen (56%) clusters contained both isolates with reduced penicillin susceptibility and penicillin-susceptible isolates, suggesting emergence of penicillin resistance. In general, there was a good correlation between ribogroups and serogroups, but 12 (48%) clusters contained isolates with alternative serogroups. Isolates with such alternative serogroups were more often encountered in penicillin-susceptible strains (41%) than in strains with reduced susceptibility to penicillin (7%). Thirty-eight (19%) isolates (including seven penicillin-susceptible strains) showed ribotypes indistinguishable from those of two international epidemic clones of S. pneumoniae: ribogroup 54-S-1 (15 isolates) with a ribopattern characteristic of the 23F multiresistant 'Spanish/USA' clone and ribogroup 74-S-3 (23 isolates) with a pattern similar to that of the 6B multiresistant 'Spanish' clone.

The present study describes the carriage patterns and genetic variability of Moraxella catarrhalis strains isolated from children living in different countries. Moraxella catarrhalis is genetically heterogeneous, but little is known about its geographic distribution and phenotypic and genetic diversity in warm-climate countries. A collection of 99 isolates from 30 Brazilian, 19 Angolan and 50 Dutch healthy children, all less than 5 years of age, was investigated for phenotypic and genotypic relatedness. The isolates from the three countries were similar where biochemical reactivity was concerned: 89 strains were beta-lactamase-producing and 87 were complement-resistant as determined by phenotype. There was no geographical difference in the prevalence of beta-lactamase-producing isolates, but the carriage rate of complement-resistant strains was significantly higher in Dutch than in Angolan children (P=0.004). Complement resistance of 66 randomly selected strains was genetically confirmed in a Southern hybridization assay by a novel DNA probe that is specific for complement-resistant strains and that demonstrated a sensitivity of 97% and a specificity of 100%. PCR amplification based on the probe sequence had a sensitivity of 98% and a specificity of 57% when compared to the outcome of a conventional culture spot test. PCR restriction fragment length polymorphism analysis of the MU 46 locus and pulsed-field gel electrophoresis of SpeI DNA macrorestriction fragments revealed genetic heterogeneity of strains from within and between the three countries, and no geographical clustering could be established. In conclusion, similar phenotypic characteristics but genotypic heterogeneity was found among Moraxella catarrhalis strains colonizing children in three different continents.

Community-acquired pneumonia from enteric gram-negative bacilli is more common in developing than in industrialized countries. We investigated the nasopharyngeal flora in healthy children from Angola, Brazil and The Netherlands to see whether enteric gram-negative bacilli are more often part of the commensal flora in developing countries. Nasopharyngeal specimens were collected from children aged between 4 months and 5 years in day-care centres and immunization clinics. Children who had received antibiotics or were malnourished were excluded. Brazilian and Angolan children had a higher number of household members than Dutch children (5.5 and 7 vs 3.9 mean number of household members, respectively) (p < 0.0001). Enteric and non-fermentative gram-negative bacilli were much more prevalent in Brazilian (50%) and Angolan (57%) children than in Dutch (4%) children (p < 0.0001). By univariate analysis, carriage of enteric gram-negative bacilli was associated with the number of household members (r = 0.26; p < 0.001). The high carriage rate of enteric gram-negative bacilli in children from Angola and Brazil may explain why enteric gram-negative bacilli are a common cause of pneumonia in developing countries.