Prospective evaluation of a model of prediction of invasive bacterial infection risk among children with cancer, fever, and neutropenia.

A risk prediction model for invasive bacterial infection (IBI) was prospectively evaluated among children presenting with cancer, fever, and neutropenia. The model incorporated assessment of 5 previously identified risk factors: serum level of C-reactive protein (CRP) >/=90 mg/L, hypotension, identification of relapse of leukemia as the cancer type, platelet count of

Rotavirus-associated medical visits and hospitalizations in South America: a prospective study at three large sentinel hospitals.

BACKGROUND: Knowledge of the impact of rotavirus-associated disease on the health care systems of South America can aid in defining strategies for diagnosis, management and prevention. Up to date information on the impact of rotavirus disease in South America is scarce. AIM: To determine prospectively the impact of rotavirus disease as a cause of medical visits and hospitalizations at three large sentinel pediatric hospitals in Argentina, Chile and Venezuela. METHODS: A 2-year prospective surveillance for rotavirus-associated medical visits and hospitalizations was conducted during 1997 through 1998 at three large sentinel public hospitals, one each in Argentina, Chile and Venezuela. A common surveillance protocol was implemented at the three sites, and a representative number of nonbloody diarrhea stool samples from children <36 months of age were tested for rotavirus by enzyme-linked immunosorbent assay. RESULTS: For our target age group, acute diarrhea-associated medical visits/hospitalizations represented 41%/2%, 5%/6% and 9%/13% of all medical visits/all hospitalizations at the Argentinean, Chilean and Venezuelan sites, respectively (P < 0.001 for difference among the three sites). Rotavirus detection rates among a total of 5,801/1,256 medical visit/hospitalization diarrhea stool samples tested were 39%/71% in Argentina, 34%/47% in Chile and 29%/38% in Venezuela (P < 0.01 by chi square for difference among the three sites). Rotavirus was associated with a mean of 1.5, 1.8 and 3% of total medical visits and 1.6, 2.8 and 5% of hospitalizations among children <36 months of age at the Argentinean, Chilean and Venezuelan sites, respectively. Seasonality was evident for medical visits at all three sites (although less striking in Chile) with peak activity occurring between November and May. Rotavirus-associated hospitalizations had a marked peak in Venezuela, represented largely by short stays, but not in Argentina and Chile. CONCLUSIONS: Rotavirus was a significant cause of medical visits at all three sentinel sites. Rotavirus caused less hospitalizations than previously reported in Argentina and Chile. On the basis of our findings we estimate that approximately 106,000/ 21,000, 48,000/8,000 and 98,000/31,000 rotavirus-associated medical visits/hospitalizations occur yearly in Argentina, Chile and Venezuela, respectively.

Prospective, multicenter evaluation of risk factors associated with invasive bacterial infection in children with cancer, neutropenia, and fever.

PURPOSE: To identify clinical and laboratory parameters present at the time of a first evaluation that could help predict which children with cancer, fever, and neutropenia were at high risk or low risk for an invasive bacterial infection. PATIENTS AND METHODS: Over a 17-month period, all children with cancer, fever, and neutropenia admitted to five hospitals in Santiago, Chile, were enrolled onto a prospective protocol. Associations between admission parameters and risk for invasive bacterial infection were assessed by univariate and logistic regression analyses. RESULTS: A total of 447 febrile neutropenic episodes occurred in 257 children. Five parameters were statistically independent risk factors for an invasive bacterial infection. Ranked by order of significance, they were as follows: C-reactive protein levels of 90 mg/L or higher (relative risk [RR], 4.2; 95% confidence interval [CI], 3.6 to 4.8); presence of hypotension (RR, 2.7; 95% CI, 2.3 to 3.2); relapse of leukemia as cancer type (RR, 1.8, 95% CI, 1.7 to 2.3); platelet count less than or equal to 50,000/mm(3) (RR, 1.7; 95% CI, 1.4 to 2.2); and recent (< or = 7 days) chemotherapy (RR, 1.3; 95% CI, 1.1 to 1.6). Other previously postulated risk factors (magnitude of fever, monocyte count) were not independent risk factors in this study population. CONCLUSION: In a large population of children, common clinical and laboratory admission parameters were identified that can help predict the risk for an invasive bacterial infection. These results encourage the possibility of a more selective management strategy for these children.

Cefepime in the empiric treatment of meningitis in children.

BACKGROUND: Because the introduction of extended spectrum cephalosporins into pediatric practice offers a number of choices for treatment, we review efficacy studies of cefepime monotherapy in the treatment of bacterial meningitis in children. METHODS: Two open, randomized, comparative studies assessed the efficacy of cefepime empiric monotherapy in the treatment of bacterial meningitis in 345 pediatric patients. These studies were conducted in Latin America and compared cefepime (50 mg/kg/dose every 8 h) with either cefotaxime (50 mg/kg/dose every 6 h) or ceftriaxone (50 mg/kg/dose every 12 h). Patients 2 months to 14 years old who had clinical signs and symptoms consistent with a central nervous system infection were enrolled. Efficacy was based on clinical and bacteriologic response. RESULTS: Integrated results from the Latin American studies indicated a 75% cure rate with cefepime vs. a 78% cure rate with comparator, among evaluable patients. Overall the rate of treatment failure was 12%. Haemophilus influenzae had the highest bacterial eradication rate (97% overall), and rates were comparable in cefepime and comparator arms. Eradication rates for Neisseria meningitidis were equally high in both treatment arms (95% overall), and the eradication rate for Streptococcus pneumoniae was 92% overall. Of the patients with S. pneumoniae isolated during pretreatment (from either cerebrospinal fluid or blood), 11 (16 isolates in total) had their isolates tested against penicillin and all were susceptible. Presence or absence of seizures, level of consciousness, Glasgow Coma Score and duration of signs and symptoms were strong predictors of outcome. Collectively no specific safety concerns were identified. CONCLUSION: Cefepime represents an important therapeutic option for the empiric treatment of bacterial meningitis in children, based on the good clinical response and bacteriologic eradication rates observed in this review.

[Achievements and challenges of the expanded immunization program in the Americas]. / Logros y desafíos del programa ampliado de inmunizaciones en la región de las Américas.

The Expanded Program on Immunization (EPI) was initiated in 1974 in The Americas, based on the WHA 2757 resolution passed by the World Assembly of Health. Its purpose was to improve immunization coverage and to decrease morbidity and mortality caused by vaccine preventable diseases through vaccination. Specific goals were to eradicate in determined time periods poliomyelitis, measles, neonatal tetanus, to eliminate tuberculous meningitis in children four years and younger, diphtheria, and tetanus. This article presents up to date information on vaccination coverage trends between 1990 and 1998 in 13 countries of the American Region, briefly describes implementation of surveillance programs required for appropriate monitoring of vaccine impact, and discusses the changes observed in morbidity attributable to vaccine preventable disease in these countries during four periods, 1968 before the existence of EPI, 1978, four years after its introduction, 1988 and 1998. Although much remains to be done, the impact of EPI in the Americas has been outstanding in decreasing morbidity caused by vaccine preventable diseases.

Human caliciviruses are a significant pathogen of acute sporadic diarrhea in children of Santiago, Chile.

Human caliciviruses (HuCVs) are increasingly recognized as common pathogens that cause acute sporadic diarrhea in children; however, regional antigenic and genetic diversity complicate detection techniques. Stool samples from children seeking medical attention in 2 outpatient clinics, a large emergency department, and 2 hospital wards were evaluated for HuCVs by reverse transcription-polymerase chain reaction, using primers based on a conserved sequence of the polymerase region of a previously sequenced Chilean strain. HuCVs were detected in 53 (8%) of 684 children 1 month to 5 years of age (mean, 13 months). Detection occurred year-round without a clear seasonal peak, and detection frequency declined from 16% in 1997 to 2% in 1999. The decline may have been due to a change in virus genotype. HuCVs are a significant pathogen of acute sporadic diarrhea in Chilean children, and continuous characterization of genetic diversity will be crucial for appropriate detection.

Genomic and antigenic variation among rotavirus strains circulating in a large city of Argentina.

Knowledge of the antigenic diversity of rotaviruses circulating in a region should be acquired before introducing a rotavirus vaccine. In a collection of 151 rotavirus-positive samples from Mendoza, Argentina, strain diversity was evaluated utilizing G-typing monoclonal antibodies (MAbs), reverse-transcriptase-polymerase chain reaction (RT-PCR) G and P typing, and electropherotyping (PAGE). The G type of 137 (91%) specimens was determined. Typing MAb reactivity with the homologous type ranged from 25-94%. For the seven G1 MAbs utilized, 28 patterns of reactivity among 68 G1 strains occurred. For the 48 G2 strains, six patterns of reactivity occurred utilizing three G2-specific MAbs. Of the 92 samples G- and P-typed by reverse-transcriptase-polymerase chain reaction, 89% had single G/P combinations: eight G1[P4], one G1[P6], twelve G1[P8], 58 G2 [P4], and two G2 [P6]. Nine samples had more than one G type with a single P type, one sample had two P types associated with one G type, and one sample contained multiple G and P types. Twenty-nine PAGE patterns occurred for all G types, but differences of antigenic reaction did not predict differences in migration of gene segments 7, 8, and 9. For three specimens showing discordant results between G type by enzyme-linked immunosorbent assay (EIA) and RT-PCR, we observed unexpected electropherotypes. Complementary evaluation by RT-PCR and MAb-based EIA with multiple typing MAbs revealed genetic and antigenic diversity of circulating rotaviruses, including extensive intratypic variation of the G1 and G2 neutralization antigens, in Mendoza during a single season of rotavirus activity.

Variability of human milk neutral oligosaccharides in a diverse population.

BACKGROUND: A complex array of free oligosaccharides is a distinctive compositional feature of human milk. Although these oligosaccharides have been studied for several years, their variability and distribution have not been systematically studied, and their nutritional and functional roles have not been elucidated. This report describes a study in which a large number of human milk samples were analyzed for the presence and content of nine neutral oligosaccharides. The resultant data were used to probe for distribution trends by donor groups and stage of lactation. METHODS: Milk samples from 435 women residing in 10 countries were analyzed using a simple preparation procedure, gel filtration, and high-performance anion-exchange chromatography. RESULTS: All samples contained structures based on lacto-N-neotetraose and lacto-N-tetraose. This contrasts with the fucosyloligosaccharides tested, none of which was detected in 100% of the samples. Unexpected distribution trends were observed. For example, 100% of the samples from Mexico (n = 156) contained 2'-fucosyllactose, whereas only 46% of the samples from the Philippines (n = 22) contained this structure. Concentration ranges for the analyzed oligosaccharides revealed quantitative and qualitative distribution trends. CONCLUSIONS: The oligosaccharide composition of human milk varied among samples. The geographical origin of the donors was one of the factors that accounted for this variability. This can be explained by genetically determined traits that are not uniformly distributed. Results indicated that further systematic studies are needed to ascertain the effect of other factors, such as lactation stage or diet.

Genotypic survey of recent beta-lactam-resistant pneumococcal nasopharyngeal isolates from asymptomatic children in Chile.

To assess pneumococcal strain variability among young asymptomatic carriers in Chile, we used serotyping, antibiotic susceptibility testing, and genotyping to analyze 68 multidrug-resistant pneumococcal isolates recovered from 54 asymptomatic children 6 to 48 months of age. The isolates represented capsular serotypes 19F (43 isolates), 14 (14 isolates), 23F (7 isolates), 6B (3 isolates), and 6A (1 isolate). Genotypic analysis, which included pulsed-field gel electrophoresis (PFGE) of chromosomal digests, penicillin binding protein (PBP) gene fingerprinting, and dhf gene fingerprinting, revealed that the isolates represented six different genetic lineages. Clear circumstantial evidence of capsular switching was seen within each of four of the genetically related sets. The majority of the isolates, consisting of the 43 19F isolates and 2 type 6B isolates, appeared to represent a genetically highly related set distinct from previously characterized pneumococcal strains. Each of three other genetically defined lineages was closely related to one of the previously characterized clones Spain(6B)-2, France(9V)-3, or Spain(23F)-1. A fifth lineage was comprised of four type 23F isolates that, by the techniques used for this study, were genetically indistinguishable from three recent type 19F sterile-site isolates from the United States. Finally, a sixth lineage was represented by a single type 23F isolate which had a unique PFGE type and unique PBP and dhf gene fingerprints.

[Detection of Norwalk and Mexico viruses, two human Caliciviruses in stools of Chilean children]. / Detección de virus Norwalk y México, dos calicivirus humanos en deposiciones de niños chilenos.

BACKGROUND: Human calciviruses (HuCVs) cause diarrhea outbreaks associated with consumption of contaminated food and water. Seroepidemiological studies in developing countries, suggest that HuCVs can cause acute gastroenteritis in children. AIM: To study the presence of Norwalk (NV) and Mexico (MX) virus, two HuCVs, in stools of Chilean children from different settings. SUBJECTS AND METHODS: ELISA tests for NV and MX were performed in 677 stool samples for children aged 0 to 132 years old, with acute diarrhea occurring in day care centers or consulting in outpatient clinics or emergency rooms. We also studied eight samples from children involved in a diarrhea outbreak that occurred in a rural community in 1992. A subset of samples was tested with polymerase chain reactions using different primers. RESULTS: Only one sample from a child with acute diarrhea occurring in a day care center was positive for HuCV by polymerase chain reaction. Three samples from the outbreak were positive by the latter method and by ELISA. The HuCV obtained from the day care center was genetically different from other known HuCV. CONCLUSIONS: Despite the high seroprevalence, NV and MX viruses were detected in a very low proportion of Chilean children stools.

Seroprevalence of Norwalk virus and Mexico virus in Chilean individuals: assessment of independent risk factors for antibody acquisition.

Norwalk virus (NV) and Mexico (MX) virus represent distinct genetic clusters within the same genus of human caliciviruses (CVs), a major cause of diarrhea in adults. The magnitude and potential risk factors of human CV infection in populations from Santiago and Punta Arenas, Chile, were assessed. Individuals (n = 1,864) gave a blood sample and answered a questionnaire during a household survey. Sera were tested for antibody to NV and MX virus with use of recombinant capsid antigens. Overall, NV and MX virus seroprevalence rates were 83% and 91% in Santiago vs. 67% and 90% in Punta Arenas, respectively (P < .001 for NV virus). Lower socioeconomic status and increasing age were risk factors for infection with both viruses (P < .001). Consumption of seafood, consumption of vegetables, and child care center attendance were population risk factors for infection, but the association of a factor with a virus depended on the city. Prevention of human CV infections will require individual assessment in different communities.

Prevalence of astrovirus infection among Chilean children with acute gastroenteritis.

The frequency of astrovirus infection in 456 Chilean children with diarrhea was determined by enzyme-linked immunosorbent assay, reverse transcriptase PCR, and cell culture. Astrovirus was detected in 16.5% of rotavirus-negative and 7% of rotavirus-positive samples obtained from emergency rooms or hospitals and in 11% of samples from day care centers. HAst-1 was the predominant serotype identified.

Molecular epidemiology of human rotaviruses in Santiago, Chile.

BACKGROUND: Protective immunity against rotavirus infection is directed against antigenic epitopes on the outer capsid proteins VP7 and VP4. Our aim was to characterize the epidemiology of rotavirus antigenic types over time in Santiago, Chile. METHODS: We prospectively obtained 2097 stool samples for rotavirus testing, VP7 (G1 to G4) and VP4 (P4, P6, P8, P9) typing from children with diarrhea evaluated in emergency rooms of 5 base hospitals of Santiago. In addition 256 rotavirus-positive samples collected between 1985 and 1987 in the north health care area of Santiago were studied. RESULTS: Of 995 rotavirus-positive samples obtained 825 (82%) were typable for 1 or more VP7 types. G1 represented 81% of the G-typed samples during 1993 through 1995 and 77% during 1985 through 1987, predominating in all health care areas. G2 was next most common in all 5 areas, representing 6 to 23% of typed samples, with 1 area, the Southeast concentrating a significantly higher number of G2 infections. G2 declined from 35% of rotavirus-positive samples in 1993 to 0% in 1995 (P < 0.001), and from 25% to 2% in the north health care area from 1985 to 1987 (P < 0.001). G4 was uncommon and significantly more prevalent in 1985 through 1987 than in 1993 through 1995 (7% vs. 3%, P = 0.015). G3 was not detected. G1P8 (53%) and G2P4 (16%) combinations were by far the most commonly detected G-P associations. CONCLUSIONS: In Santiago, Chile, rotavirus antigenic type G1P8 has been highly prevalent and G2P4 has circulated in cycles. Differences in epidemiology of rotavirus antigenic types worldwide may prove to be relevant in efficacy of rotavirus vaccines.

Effect of maternal rotavirus immunization on milk and serum antibody titers.

This prospective study evaluated human milk and serum antirotavirus antibody concentrations following maternal rotavirus immunization. Postpartum women (33) were randomized into 3 groups and received a single oral dose of rhesus rotavirus monovalent reassortant vaccine (10(4) pfu), tetravalent vaccine (10(4) pfu), or placebo. Milk (secretory [s] IgA) and serum (IgA and IgG) specimens were tested for antirotavirus isotype-specific antibody. Sera also were tested for G1- to G4-specific antibody. Prevaccine milk and serum isotype-specific antibody concentrations were not significantly different in the 3 groups. Postvaccine sIgA log titers were significantly greater in the 2 vaccine groups than the placebo group (P = .002). Mean log10 titers at 1 week were 2.1 (95% confidence interval [CI], 2.0-2.3) in the 2 vaccine groups and 1.7 (95% CI, 1.5-1.9) in the placebo group. Milk titers did not differ between vaccine groups. There was no difference in reactogenicity between groups. The significantly higher milk concentrations of antibody to rotavirus in postpartum women who received rotavirus immunization persisted for 4 months.

[Antigenic types of circulating rotavirus in children with acute diarrhea in Santiago de Chile]. / Tipos antigénicos de rotavirus circulantes en niños con diarrea aguda en Santiago de Chile.

Protective immunity against rotavirus infection is directed against antigenic epitopes on the outer capsid proteins VP7 and VP4. The aim of this study was to characterize the VP7 and VP4 antigenic types circulating in different hospital areas of Santiago, Chile, over different time periods. Between April 1993 and April 1994 a total of 1206 stool samples were obtained from children consulting for acute no bloody diarrhea in 5 hospitals representative of the 5 major health areas of Santiago. In addition, 256 rotavirus positive samples, obtained from children with acute diarrhea consulting in the north health area of Santiago between 1985-1987 were studied. All samples were processed for rotavirus by an ELISA and all rotavirus positive samples were VP7 typed (types G1-G4) by a monoclonal antibody based ELISA. 50 rotavirus positive samples were selected for VP4 typing by PCR (types P1-P4). A total of 782 rotavirus positive samples were obtained of which 618 (79%) were typable for one specific VP7 type. VP7 type G1 represented 63% of the rotavirus positive samples and predominated in all areas evaluated throughout the entire period of observation. VP7 type G2 represented 13% of rotavirus samples, following G1 in predominance. G2 types decreased progressively in all areas in both study periods. G4 types were detected mainly during 1985-1987, and G3 types have so far not been detected. Preliminary analysis of VP4 types suggests that P1 types are predominant and closely associated with VP7 G1 type. These results are relevant for the adoption of appropriate preventive strategies for rotavirus infection, specifically aimed to the development of effective vaccines.