Pneumococcal carriage among indigenous Warao children in Venezuela: serotypes, susceptibility patterns, and molecular epidemiology.

Little attention has been paid to pneumococcal carriage and disease in Amerindians from Latin America. The Warao people, an indigenous population from Venezuela, live in the delta of the Orinoco River in geographically isolated communities with difficult access to medical care. To obtain insight into pneumococcal carriage and the theoretical coverage of pneumococcal vaccines in this population, we investigated pneumococcal colonization, serotype, and genotype distribution among Warao children in 9 distinct, geographically isolated communities in the Delta Amacuro area in the northeast of Venezuela. From April 2004 through January 2005, a total of 161 Streptococcus pneumoniae isolates were recovered from single nasopharyngeal swab samples obtained from 356 children aged 0-72 months. The overall pneumococcal carriage rate was 49%, ranging from 13% to 76%, depending on the community investigated and the age of the children (50% among children aged <2 years and 25% among children aged >2 years). The most frequent serotypes were 23F (19.5% of isolates), 6A (19.5%), 15B (10.4%), 6B (9.1%), and 19F (7.2%). The theoretical coverage of the 7-valent pneumococcal conjugate vaccine, including the cross-reactive nonvaccine serotype 6A, was 65%. A total of 26% of the isolates were resistant to first-line antibiotics, with 70% of these strains being covered by the 7-valent pneumococcal conjugate vaccine. Restriction fragment end labelling analysis revealed 65 different genotypes, with 125 (80%) of the isolates belonging to 27 different genetic clusters, suggesting a high degree of horizontal spread of pneumococcal strains in and between the villages. The high colonization rates and high (registered) acute respiratory tract infection morbidity and mortality in this part of Venezuela suggest that Warao children are at increased risk for pneumococcal disease and, therefore, benefit from vaccination.     

Short stature caused by SHOX gene haploinsufficiency: from diagnosis to treatment

Studies involving patients with short stature and partial deletion of sex chromosomes identified SHOX gene in the pseudoautosomal region of the X and Y chromosomes. SHOX haploinsufficiency is an important cause of short stature in a diversity of clinical conditions. It explains 2/3 of short stature observed in Turner syndrome (TS) patients. Heterozygous mutations in SHOX are observed in 77% of patients with Leri-Weill dyschondrosteosis, a common dominant inherited skeletal dysplasia and in 3% of children with idiopathic short stature, indicating that SHOX defects are the most frequent monogenetic cause of short stature. The sitting height/height ratio (SH/H) standard deviation score is a simple way to assess body proportions and together with a careful exam of other family members, effectively selected a group of patients that presented a high frequency of SHOX mutations. Growth hormone treatment of short stature due to TS is well established and considering the common etiology of short stature in patients with isolated defects of SHOX gene, this treatment is also proposed for these patients. Here, we review clinical, molecular and therapeutic aspects of SHOX haploinsufficiency.     

Impacto pronóstico diferencial del infarto de miocardio comparado con la gravedad de la hemorragia sobre la mortalidad en pacientes contemporáneos con síndrome coronario agudo

Introduction and objectives

The impact on mortality of myocardial infarction (MI) compared with the specific degree of bleeding severity occurring after discharge in acute coronary syndrome is poorly characterized. Defining this relationship may help to achieve a favorable therapeutic risk-benefit balance.

Complete Genome Analysis of a Rabbit Rotavirus Causing Gastroenteritis in a Human Infant

Group A rotaviruses (RVA) are responsible for causing infantile diarrhea both in humans and animals. The molecular characteristics of lapine RVA strains are only studied to a limited extent and so far G3P[14] and G3P[22] were found to be the most common G/P-genotypes. During the 2012-2013 rotavirus season in Belgium, a G3P[14] RVA strain was isolated from stool collected from a two-year-old boy. We investigated whether RVA/Human-wt/BEL/BE5028/2012/G3P[14] is completely of lapine origin or the result of reassortment event(s). Phylogenetic analyses of all gene segments revealed the following genotype constellation: G3-P[14]-I2-R2-C2-M3-A9-N2-T6-E5-H3 and indicated that BE5028 probably represents a rabbit to human interspecies transmission able to cause disease in a human child. Interestingly, BE5028 showed a close evolutionary relationship to RVA/Human-wt/BEL/B4106/2000/G3P[14], another lapine-like strain isolated in a Belgian child in 2000. The phylogenetic analysis of the NSP3 segment suggests the introduction of a bovine(-like) NSP3 into the lapine RVA population in the past 12 years. Sequence analysis of NSP5 revealed a head-to-tail partial duplication, combined with two short insertions and a deletion, indicative of the continuous circulation of this RVA lineage within the rabbit population.     

Streptococcus salivarius K12 Limits Group B Streptococcus Vaginal Colonization

Streptococcus agalactiae (group B streptococcus [GBS]) colonizes the rectovaginal tract in 20% to 30% of women and during pregnancy can be transmitted to the newborn, causing severe invasive disease. Current routine screening and antibiotic prophylaxis have fallen short of complete prevention of GBS transmission, and GBS remains a leading cause of neonatal infection. We have investigated the ability of Streptococcus salivarius, a predominant member of the native human oral microbiota, to control GBS colonization. Comparison of the antibacterial activities of multiple S. salivarius strains by use of a deferred-antagonism test showed that S. salivarius strain K12 exhibited the broadest spectrum of activity against GBS. K12 effectively inhibited all GBS strains tested, including disease-implicated isolates from newborns and colonizing isolates from the vaginal tract of pregnant women. Inhibition was dependent on the presence of megaplasmid pSsal-K12, which encodes the bacteriocins salivaricin A and salivaricin B; however, in coculture experiments, GBS growth was impeded by K12 independently of the megaplasmid. We also demonstrated that K12 adheres to and invades human vaginal epithelial cells at levels comparable to GBS. Inhibitory activity of K12 was examined in vivo using a mouse model of GBS vaginal colonization. Mice colonized with GBS were treated vaginally with K12. K12 administration significantly reduced GBS vaginal colonization in comparison to nontreated controls, and this effect was partially dependent on the K12 megaplasmid. Our results suggest that K12 may have potential as a preventative therapy to control GBS vaginal colonization and thereby prevent its transmission to the neonate during pregnancy.     

Complete form of androgen insensitivity syndrome in Brazilian patients due to P766A mutation in the androgen receptor

Androgen insensitivity syndrome (AIS) is a rare X-linked disorder, caused by mutations in the androgen receptor gene (AR), associated with a variety of phenotypes in 46,XY individuals. We studied two 23 year-old twin-sisters with female social sex referred due to primary amenorrhea, who exhibited bilateral palpable gonads in the inguinal region and a 46,XY karyotype. The uterus was absent in pelvic sonograms. Basal LH levels were elevated (35 and 42 U/L), with normal FSH (7.9 and 7.8 U/L) and high testosterone levels (1330 and 1660 ng/dl). The molecular analysis identified a missense mutation in exon 5 of AR gene that changed a proline to an alanine at position 766 of the protein. Proline 766 is a highly conserved amino acid in the AR of several species and is located in the androgen binding domain.     

Nelson's Syndrome: a case report

The aim of this article is to present and discuss several aspects of the pathogenesis, the clinical, hormonal, and imaging diagnosis, and the treatment of Nelson's syndrome, based on a typical patient's report, in whom several therapeutic approaches were shown to be ineffective.     

Polymorphisms identified in the upstream core polyadenylation signal of IGF1 gene exon 6 do not cause pre- and postnatal growth impairment

BACKGROUND: Few children born small for gestational age (SGA) with IGF1 mutations have been reported. One of these patients presented a mutation at 3' untranslated region (UTR) at exon 6, probably affecting the polyadenylation process. OBJECTIVE: The objective of the study was to sequence the IGF1 gene of children born SGA. PATIENTS AND METHODS: IGF1 (exons 1-6) was directly sequenced in 53 SGA children without catch-up growth. Allelic variant frequency of the identified IGF1 polymorphisms was assessed in a total of 145 SGA children and in 180 controls born with adequate weight and length and adult height sd score greater than -2. RESULTS: No mutations were identified in the IGF1 coding regions in SGA children. In contrast, six allelic variants were identified in the upstream core polyadenylation signal located in IGF1 3' UTR at exon 6. The frequency of the different allelic variants was similar in SGA children and controls. It is noteworthy that the same allelic variant, previously described as causing severe IGF1 deficiency, was also observed in homozygous (n = 4) and heterozygous state (n = 6) in normal height controls, corresponding to 4% of studied alleles. The three most frequently identified allelic variants of IGF1 3' UTR showed no effect on height sd score of adult controls as well as on birth characteristics in SGA children. CONCLUSION: The polymorphisms identified in the upstream core polyadenylation signal at IGF1 exon 6 do not cause IGF1 deficiency as well as pre- and postnatal growth impairment, in contrast to previously reported data.