Serogroup W meningococcal disease: global spread and current affect on the Southern Cone in Latin America.

Meningococcal serogroup W strains have been emerging throughout the current century with most of the isolates belonging to the sequence type (ST11)/electrophoretic type (ET37) clonal complex (ST11/E37 CC), particularly since the international outbreak following Hajj 2000. That outbreak appears to have triggered off that trend, contributing to the spread of W ST11/ET37 CC strains globally; however, local strains could be also responsible for increases in the percentage and/or incidence rates of this serogroup in some countries. More recently, unexpected increases in the percentage and incidence rate of W has been noticed in different countries located in the South Cone in Latin America, and W ST11/ET37 CC strains now appear as endemic in the region and an extensive immunization programme with tetravalent conjugate vaccine (covering serogroups A, C, Y and W) has been recently implemented in Chile. It is difficult to ascertain whether we are observing the emergence of W ST11 CC strains in different geographical areas or whether the Hajj 2000 strain is still spreading globally. Several aspects of the evolution of that situation are analysed in this paper, reviewing also the implications in immunization programmes. Closely related with the analysis of this potential evolution, it will be very interesting to monitor the evolution of serogroup W in the African meningitis belt after implementation of the extensive immunization programme with serogroup A conjugate vaccine that is currently underway. More data about carriers, transmission, clonal lineages, etc. are needed for taking decisions (target groups, outbreak control, defining the extent, etc.) to adapt the response strategy with potential interventions with broad coverage vaccines against the emergent serogroup W.

Description of the pig production systems, biosecurity practices and herd health providers in two provinces with high swine density in the Philippines.

A cross-sectional study was conducted between October 2011 and March 2012 in two major pig producing provinces in the Philippines. Four hundred and seventy one pig farms slaughtering finisher pigs at government operated abattoirs participated in this study. The objectives of this study were to group: (a) smallholder (S) and commercial (C) production systems into patterns according to their herd health providers (HHPs), and obtain descriptive information about the grouped S and C production systems; and (b) identify key HHPs within each production system using social network analysis. On-farm veterinarians, private consultants, pharmaceutical company representatives, government veterinarians, livestock and agricultural technicians, and agricultural supply stores were found to be actively interacting with pig farmers. Four clusters were identified based on production system and their choice of HHPs. Differences in management and biosecurity practices were found between S and C clusters. Private HHPs provided a service to larger C and some larger S farms, and have little or no interaction with the other HHPs. Government HHPs provided herd health service mainly to S farms and small C farms. Agricultural supply stores were identified as a dominant solitary HHP and provided herd health services to the majority of farmers. Increased knowledge of the routine management and biosecurity practices of S and C farmers and the key HHPs that are likely to be associated with those practices would be of value as this information could be used to inform a risk-based approach to disease surveillance and control.

[Congenital cytomegalovirus infection]. / Infección congénita por citomegalovirus.

INTRODUCTION: Cytomegalovirus (CMV) is the most frequent cause of intrauterine infection and an important cause of auditory system damage and mental retardation in humans. Clinical presentation varies from asymptomatic form to lethal systemic dissemination. OBJECTIVES: To describe clinical and laboratories manifestations, age at the moment of diagnostic, treatment and diagnostic test used in congenital cytomegalovirus infection. POPULATION, MATERIAL AND METHODS: Observational, retrospective and descriptive study. Clinical histories of congenital CMV infected infants evaluated by Infectology Department of the Hospital General de Niños Dr. Ricardo Gutiérrez between January 2002 and December 2006 were analyzed. RESULTS: Seventeen patients were evaluated. Mean age at diagnosis was 2.6 months. The most frequent symptom/sign were hepato-splenomegaly (76 %), jaundice (47 %), petechiae and hearing deficit (41 %). Anemia (53 %) and thrombocytopenia (40 %) were the most common laboratory abnormalities. Diagnosis was made exclusively by polymerase chain reaction (PCR)-CMV in one third of the patients, whereas one third was diagnosed by serology and the other third for both test. Five patients received ganciclovir as treatment. Only one had neutropenia. CONCLUSIONS: Differential diagnosis of all newborns with hepatoesplenomegaly, jaundice and petechiae and anemia and/or thrombocytopenia must include congenital cytomegalo-virus infection. Early diagnosis allows a prompt intervention and a strict audiological follow up.

Hepatitis A vaccination of Argentinean infants: comparison of two vaccination schedules.

BACKGROUND: Early immunization to protect infants against hepatitis A (HA) is recommended in intermediate or high endemic areas of the world, but little is known of the effects of maternal antibodies on the immune response. We studied the immunogenicity and reactogenicity of an inactivated HA vaccine administered in two different schedules to 2-month-old infants in an intermediate/high endemic area in Argentina. METHODS: In this double-blind, randomized study 131 infants received either three doses (at 2, 4, 6 months of age [Group A]) or one dose (at 6 months of age [Group B]) of the pediatric inactivated HA vaccine, Avaxim 80, and a booster dose at 15-18 months. HAV antibodies were measured (ELISA) at 2, 7, 15-18 and 16-19 months of age. Immediate (30 min after injection) and solicited local and systemic reactions were recorded for 7 days after each injection. RESULTS: Of 107/131 subjects (81.6%) who completed the study and who provided final serum samples after booster dose, 94 (87.8%) were seropositive at enrolment (>20 mIU/mL) with geometric mean concentrations (GMC) of 2989 and 3637 mIU/mL in Groups A and B, respectively. One month post-booster GMCs were 8236 mIU/ml (95% CI; 6304, 10760) and 1687 mIU/ml (1148, 2479) in Groups A and B, respectively, with 100% seroprotection. CONCLUSIONS: The HA vaccine was well tolerated and induced immunological priming in both groups during the first year of life in spite of the presence of maternal antibodies. Post-booster GMCs achieved after one or three primary doses suggest a long-term protection against HA.

Safety and immunogenicity of a pediatric formulation of inactivated hepatitis A vaccine in Argentinean children.

BACKGROUND: Children are a reservoir of hepatitis A virus and must be considered as primary targets of any immunization strategy. The safety and immunogenicity were evaluated for a new formulation of an inactivated hepatitis A vaccine, Avaxim 80 units, containing one-half the antigen dose of the adult formulation. METHODS: The safety of two doses of this vaccine given 6 months apart was evaluated in an open study in 537 Argentinean children 12 months to 15 years old. Immunogenicity was evaluated at Weeks 0, 2, 24 and 27 in a subgroup of 120 subjects. RESULTS: Two weeks after the first vaccine dose, >99% of initially seronegative children had seroconverted (titers > or =20 mIU/ml), with a geometric mean titer of 98.5 mIU/ml. Before booster at 24 weeks all subjects had seroconverted. A strong anamnestic response was observed after the second dose at which time the geometric mean titer had increased >35-fold, and antibody titers were consistent with long term protection. Immediate adverse reactions were observed in 3 of 537 (0.6%) subjects after the first dose. Local reactions were mild and transient and did not increase with subsequent doses. Among the systemic events reported during the 7-day follow-up period, 37 cases of fever after the first dose and 22 cases after the second dose were reported. Only 3 cases of fever were clearly related to vaccination (< or =38.2 degrees C) after the first injection, all of which subsided in less than 1 day. CONCLUSIONS: This study demonstrated the safety and immunogenicity of a pediatric formulation of hepatitis A vaccine in children ages 12 months to 15 years in healthy children ages 12 to 47 months.

Shigella and Shiga toxin-producing Escherichia coli causing bloody diarrhea in Latin America.

In Latin America, Shigella and shiga toxin-producing Escherichia coli are the two leading agents in the cause of bloody diarrhea. The already high and increasing antimicrobial resistance of Shigella also is a significant problem. Shiga toxin-producing E. coli is an emerging disease with life-threatening complications: hemolytic uremic syndrome. Although E. coli O157:H7 remains the most commonly recognized serotype, recently emerging, non-O157 bacteria may be the cause of a similar spectrum of disease in humans.

Incomplete hemolytic-uremic syndrome in Argentinean children with bloody diarrhea.

Argentina has an exceptionally high frequency of hemolytic-uremic syndrome (HUS). We sought to define prospectively the role of verocytotoxins (Shiga-like toxins [SLTs]) in 254 Argentinean children with grossly bloody diarrhea during spring and summer. Free fecal SLTs (I/II) and/or DNA probe-positive isolates were found in 99 (39%) of the children. During the follow-up period, HUS developed in 6 patients (4 with evidence of recent SLT infection based on stool studies); another 14 patients had some, but not all, of the abnormalities seen in typical HUS. The development of HUS or incomplete HUS in these children was significantly associated with recent SLT-Escherichia coli infection (p = 0.024). The high incidence of SLT-associated bloody diarrhea in Argentina explains, at least partially, the unusually high frequency of HUS. Our data indicate that incomplete forms of HUS may be common in patients with SLT-associated bloody diarrhea.

Tumor necrosis factor concentrations in hemolytic uremic syndrome patients and children with bloody diarrhea in Argentina.

Hemolytic uremic syndrome (HUS) is thought to be a vascular endothelial injury disease. The mechanism of injury is unknown although verocytotoxins (Shiga-like toxins (SLTs)) are known to be associated with it. Recent evidence suggests that in vitro treatment of some endothelial cells with tumor necrosis factor alpha (TNF-alpha) dramatically increases their susceptibility to SLTs. We studied 25 children with HUS, 63 children with SLT-positive bloody diarrhea, 62 children with bloody diarrhea not associated with SLTs and 39 children admitted for elective surgery, included as an age- and season-matched control group. The TNF-alpha concentrations were found to be significantly elevated in children with HUS (range, 1 to 95 pg/ml; geometric mean, 32.2 pg/ml) compared with the healthy controls (range, 0 to 53 pg/ml; mean, 12.5 pg/ml; P < 0.001). Because it is hypothesized that TNF-alpha elevation might precede development of HUS, we also studied children with blood diarrhea. The TNF-alpha serum concentrations were significantly higher during the first 10 days after onset of bloody diarrhea than after the first 10 days (P < 0.02). Such elevation could be associated with vascular endothelial glycolipid receptor up-regulation and increased susceptibility to the effects of SLTs.

Susceptibility to hemolytic-uremic syndrome relates to erythrocyte glycosphingolipid patterns.

Hemolytic-uremic syndrome (HUS) is usually preceded by enteric infection by Shiga-like toxin-producing Escherichia coli (SLT-EC), but most children with SLT-EC diarrhea do not develop HUS. SLT toxicity depends on entry into the target cell via its host cell glycolipid receptor, globotriaosylceramide (Gb3). The relationship between differential susceptibility to HUS and erythrocyte Gb3 levels, as measured by high-pressure liquid chromatography, was studied. Erythrocytes of children with histories of HUS had lower nonhydroxylated fatty acyl (NFA) Gb3 levels than did erythrocytes of controls (1.6 vs. 2.0 nmol/mL of packed cells); these erythrocytes had lower ratios of NFA-Gb3 to lactosylceramide (0.16) than did erythrocytes of SLT-EC diarrheal patients without subsequent HUS (0.30; P < .003) or of healthy controls (0.28; P < .001). The lower erythrocyte Gb3 levels associated with HUS may reflect a genetic predisposition for differential outcomes of SLT-EC gastroenteritis.

Multiply resistant nontyphoidal Salmonella gastroenteritis in children.

From January, 1990, to December 31, 1990, 75 children with multiply resistant Salmonella gastroenteritis were studied at the Children's Hospital "Ricardo Gutierrez" of Buenos Aires. These children ranged from 1 month to 15 years of age. Infection was community-acquired in 20 (26.6%), nosocomially acquired in 50 (66.7%) and undetermined in 5. Thirty-nine (52%) had grossly bloody stools. Fever occurred at some point in the clinical course in 61 children (81.3%) with a duration of 1 to 33 days (mean, 6.7 days). The duration of diarrhea (1 to 69 days) was longer in those who developed complications (P < 0.001). Six (8%) developed enterocolitis (2 with bowel perforation), 1 had a pulmonary abscess and 8 (11.4%) had bacteremia; 4 children died (5.3%). Salmonella typhimurium was the most common serovar (85.3%). Ninety percent minimum inhibitory concentration studies demonstrated that all strains were resistant to ampicillin (> 128 micrograms/ml), cephalothin (> 128 micrograms/ml), cefuroxime (> 128 micrograms/ml), nalidixic acid (> 256 micrograms/ml), rifampin (> 256 micrograms/ml), gentamicin (> 256 micrograms/ml) and tobramycin (256 micrograms/ml); 77.3% of strains were resistant to ceftazidime (32 micrograms/ml), 97.6% to netilmicin (> 256 micrograms/ml), 92.8% to amikacin (256 micrograms/ml), 24.4% to isepamicin (32 micrograms/ml), 5.3% to chloramphenicol (4 micrograms/ml) and 2.7% to cefoxitin (2 micrograms/ml). The 90% minimum inhibitory concentration of cefotaxime and ceftazidime was reduced by the addition of clavulanate. Aggressive multiply resistant Salmonella strains are a major pediatric problem in Buenos Aires.

Polymerase chain reaction for diagnosis of enterohemorrhagic Escherichia coli infection and hemolytic-uremic syndrome.

Two pairs of oligonucleotide primers were designed to amplify fragments of the genes for Shiga-like toxin I (SLT-I) and SLT-II in a single reaction. A 370-bp segment and a 283-bp segment were amplified for SLT-I and SLT-II, respectively. The specificities of the polymerase chain reaction (PCR) amplification products were confirmed by using radioactively labeled oligonucleotide probes. SLT sequences were amplified from DNA isolated from 13 previously characterized enterohemorrhagic Escherichia coli (EHEC) strains. No amplification product was produced by using DNA from 20 non-EHEC strains. As little as one bacterial genome was detectable. PCR was then applied to DNA isolated directly from stool samples. We had to remove inhibitors of PCR that were present in lysates prepared from stool samples before amplification was achieved. First, we evaluated the sensitivity of PCR for the detection of known numbers of EHEC added to normal stools. Second, three children with SLT in their stools were shown to have SLT sequences in their stools by PCR. Two of these children had hemolytic-uremic syndrome, and a third child was asymptomatic. Stool specimens collected from another 26 asymptomatic children were negative by PCR for SLT sequences. PCR can be used to diagnose EHEC infections without prior culture of stool specimens.

Association between severity of gastrointestinal prodrome and long-term prognosis in classic hemolytic-uremic syndrome.

To determine whether severity of the prodromal gastrointestinal illness is associated with the course and complications of the extraintestinal manifestations of hemolytic-uremic syndrome, we conducted a retrospective review of children (n = 509) hospitalized with hemolytic-uremic syndrome. Those who came to the hospital with colitis and rectal prolapse associated with hemolytic-uremic syndrome (group I, n = 40) were compared with an equal number of time-matched children with hemolytic-uremic syndrome but without prolapse (group II). Children in group I had evidence of more severe colitis than children in group II had, as indicated by increased frequency of bloody diarrhea (p less than 0.001) and longer duration of diarrhea (p less than 0.001). However, they also had more severe extraintestinal manifestations during hemolytic-uremic syndrome, including edema (p less than 0.0001), severe thrombocytopenia (p less than 0.0001), prolonged anuria (p less than 0.001), and seizures (p = 0.036). Long-term prognosis for recovery of renal function was worse for group I than group II. Within group II, patients with bloody diarrhea had milder extraintestinal illness than those with prolapse but more severe extraintestinal illness than those with watery diarrhea. Analysis of Kaplan-Meier survival curves demonstrated a better prognosis for return of normal renal function in the children with watery diarrhea but without prolapse (p = 0.009) than in children with bloody diarrhea or prolapse. These data demonstrate that the severity of the gastrointestinal prodrome reflects the severity of the extraintestinal acute microangiopathic process and the resulting long-term outcome. Widespread vascular damage, often followed by permanent sequelae, is characteristic of patients with the most severe colitis.

The effect of postnatal age on the adherence of enterohemorrhagic Escherichia coli to rabbit intestinal cells.

Enterohemorrhagic Escherichia coli (EHEC) are associated with hemorrhagic colitis and hemolytic uremic syndrome. These illnesses are typically seen in young children, but are rare before 6 mo of age. The cause of this age restriction is unclear. Because bacterial adherence to intestinal mucosa is considered a critical initial event in pathogenesis, we studied the ontogeny of the adherence of EHEC (O157:H7 and other serotypes) isolated from children with diarrhea, hemorrhagic colitis, or hemolytic uremic syndrome. Adherence was quantitatively determined by incubating radiolabeled bacteria with viable rabbit intestinal cells, which were prepared by treating loops of distal ileum and proximal colon with EDTA, DTT, and citrate. Cells obtained from animals of different ages were studied simultaneously. The adherence of the various EHEC strains varied significantly. A non-O157:H7 E. coli strain 43-12 bound best (35 and 32 bacteria/cell to ileal and colonic cells, respectively) with 48-60% inhibition by D-mannose and alpha-methyl mannoside (p less than 0.01) and 20-28% inhibition by L-fucose (p less than 0.05), but no significant inhibition by other carbohydrates. Analysis of variance and polynomial regression showed that postnatal age significantly affected the adherence to ileal and colonic cells. Adherence during the 1st wk of life was 13-19% of that in the adult animal; it increased gradually, reaching the adult level at about 4 wk of age. Our study shows that postnatal age affects the adherence of EHEC to intestinal cells. These findings are compatible with postnatal development of gut receptors and may be relevant to the age-related risk of EHEC disease in children.

Evidence of infection with organisms producing Shiga-like toxins in household contacts of children with the hemolytic uremic syndrome.

We conducted a prospective study in 87 household contacts of 51 children with hemolytic uremic syndrome to determine the frequency of infection with Shiga-like toxin-producing bacteria. Gastrointestinal tract symptoms occurred in only 1 of 87 contacts. Free fecal toxin was detected in 25 of 64 (39%) of the household members. Neutralization with specific antisera to Shiga-like toxins I and II (SLT-I, SLT-II) revealed that in 6 of these household contacts only SLT-I was present in stool, in 10 only SLT-II was present and in 9 both toxins were found. Thirty-three percent of the hemolytic uremic syndrome families in which 2 or more members were studied had more than 1 household member with free fecal toxin in stool. None of the household contacts was found to have E. coli O157:H7 in feces. Serum samples were available in 77 household contacts; 75% (58 of 77) had serum neutralizing titers of greater than or equal to 1:4 to 1 or both toxins. In those contacts for whom paired sera were available, seroconversion was found in 10 of 24 (42%). These data show that household contacts of children with hemolytic uremic syndrome are commonly colonized with Shiga-like toxin-producing E. coli and seroconversion to Shiga-like toxins occurs frequently in family members of children with hemolytic uremic syndrome.

Hemolytic uremic syndrome and diarrhea in Argentine children: the role of Shiga-like toxins.

Shiga-like toxin-producing Escherichia coli have been associated with hemorrhagic colitis and the hemolytic uremic syndrome (HUS). Because Argentina has the highest reported frequency of HUS in the world, Argentine children were prospectively studied during the HUS seasons for evidence of Shiga-like toxin-related diseases. On the basis of serology, fecal cytotoxin neutralization, stool cultures, and DNA hybridization of colony lysates, most children with HUS had evidence of infection with Shiga-like toxin-producing organisms. Children with spring-summer diarrhea also commonly (32%, confidence interval 18%-46%) had clear-cut evidence of such infection. No controls (children without gastrointestinal, renal, or hemolytic disease) had free fecal cytotoxin, positive cultures for E. coli O157:H7, or DNA probe-positive organisms; 20% of them had low serum titers of antibodies to Shiga-like toxins. E. coli O157:H7 was not common in either HUS or diarrhea patients. The high frequency of Shiga-like toxin-induced diarrhea in young children in Argentina probably explains the high incidence of HUS in this country and suggests that HUS is a relatively uncommon complication of Shiga-like toxin-related disease.

Computed tomography in purulent meningitis.

Of 102 patients with bacterial meningitis admitted to the Children's Hospital of Buenos Aires, 25 were selected for computed tomographic (CT) scans on the basis of altered consciousness for more than 96 hours after admission, persistent or recurrent seizures after 72 hours of antibiotic therapy, development of focal neurologic signs, increased intracranial pressure or prolonged fever. Scan findings included hydrocephalus, cerebritis, vasculitis, subdural effusion, cerebral atrophy, abscess, and ependymitis. Serial CT scans demonstrated the progression or regression of some complications. The CT scan was very useful in indicating the need for neurosurgical procedures.