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

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.

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.

[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.

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.

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.

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.

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.

[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.

[Characterization of antigenic types of circulating rotaviruses in Mendoza, Argentina based on typing of the external VP7 capsid protein]. / Caracterización de tipos antigenícos de rotavirus circulantes en Mendoza, Argentina en base a tipificación de la proteina de la capside externa VP7.

Rotavirus is one of the most common etiologic agents of acute diarrhea in childhood. Understanding the immunologic mechanisms involved in rotavirus diseases, including knowledge on seasonal and geographic antigenic variations may be crucial for vaccine development. A monoclonal antibody based ELISA specific for antigenic domains on the outer capsid protein VP7 has been developed and used widely in the past years. We studied the rotavirus VP7-serotype epidemiology causing diarrhea in children who consulted at two main hospitals of Mendoza, Argentina over a 20 month period. A total of 227 cases of diarrhea were identified, 45 of which (20%) were rotavirus positive. We're able to serotype 43 viruses (96%), 42 VP7-type 1 and one VP7-type 3. The VP7-type 3 was detected towards the end of the second year, possibly representing a new incoming VP7-type. Three electropherotype patterns were identified, two corresponding to VP7-type epidemiology in Mendoza, Argentina seems to be characterized by a relatively homogeneous pattern of circulation with a strong predominance of VP7-type 1 viruses, at least during the 20 month period studied, in contrast to what has been reported in larger, more cosmopolitan cities like Buenos Aires.

Caracterización de tipos antigenícos de rotavirus circulantes en Mendoza, Argentina, en base a tipificación de la proteína de la capside externa VP7 / Characterization of antigenic types of circulating rotavirus in Mendoza, Argentina with base to typing of external VP7 capsid protein

El rotavirus es uno de los agentes etiológicos más comunes de la diarrea aguda de la infancia. La compresión de los mecanismos inmunológicos involucrados en las enfermedades por rotavirus incluso el conocimiento de las variaciones antigénicas, estacionales y geográficas pueden ser cruciales para el desarrollo de la vacuna. Un anticuerpo monoclonal, basado en ELISA, específico para el dominio antigénico sobre la cápside exterior proteica VP7, ha sido desarrollado y usado ampliamente durante los últimos años. Estudiamos la epidemiología del rotavirus VP7, causante de diarrea en niños que consultaron en los dos hospitales principales de Mendoza, Argentina, durante un período de 20 meses. Fueron identificados 227 casos de diarrea, 45 de los cuales (20 por ciento) fueron rotavirus positivas. Pudimos determinar el serotipo de 43 virus (96 por ciento), 42 tipo VP7 y 1 tipo VP7-3. Este último fue detectado hacia el final del segundo año representando posiblemente un tipo VP7 nuevo, que llegaba. Se identificaron 3 patrones electroforéticos, dos correspondientes a la epidemia de tipo VP7 en Mendoza, parecían caracterizados por un patrón relativamente homogéneo de circulación con fuerte predominancia del virus VP7-tipo 1,por lo menos durante el período estudiado de 20 meses, en contraste con lo que se ha informado en ciudades más grandes y cosmopolitas, tales como Buenos Aires

Outbreaks of human enteric adenovirus types 40 and 41 in Houston day care centers.

OBJECTIVE: Human enteric adenovirus (EAd) types 40 and 41 cause diarrhea in young children, but little is known about their association with outbreaks of diarrhea in the child care setting. This study evaluated EAd as a cause of outbreaks of diarrhea among infants and toddlers in day care centers. DESIGN: Stool specimens were collected weekly regardless of symptoms during four periods from January 1986 to April 1991, from children 6 to 24 months of age enrolled in prospective studies of diarrhea in day care centers. All diarrhea stool specimens were tested for bacterial enteropathogens, rotavirus, and Giardia lamblia. A total of 131 outbreaks occurred during the study. No etiologic agent was identified in 77 outbreaks. Stool specimens from 75 of these 77 outbreaks and from another 21 outbreaks of diarrhea with a known cause were evaluated for EAd with a monoclonal antibody-based enzyme immunoassay. RESULTS: A total of 4402 stool specimens from 613 children from these 96 outbreaks was tested for EAd. The virus was detected in specimens collected during 10 outbreaks, 3 of which occurred in 1986, 3 in 1988, 1 in 1989, 1 in 1990, and 2 in 1991. Of 249 children, 94 (38%) in these 10 EAd outbreaks were infected with EAd. In 51 children (54%) the infection was symptomatic and in 43 (46%) it was asymptomatic. Outbreaks lasted 7 to 44 days (mean 24.5 days). Duration of EAd excretion ranged from 1 to 14 days (mean 3.9 days), with excretion occurring from 7 days (mean 2.6) before diarrhea began to 11 days (mean 5.3 days) after diarrhea stopped. CONCLUSION: Enteric adenovirus types 40 and 41 are an important cause of outbreaks of diarrhea among children attending day care centers, often involve children in more than one room, and frequently produce asymptomatic infection.

Bismuth subsalicylate in the treatment of acute diarrhea in children: a clinical study.

Bismuth subsalicylate (BSS) and placebo were evaluated in a double-blind, placebo-controlled study as adjunct to rehydration therapy in 123 children, aged 4 to 28 months, hospitalized with acute diarrhea. The dosing regimen was 20 mg/kg five times daily for 5 days. Significant benefits were noted in the BSS group compared with placebo as manifested by decreases in stool frequency and stool weights and an improvement in stool consistency, significant improvement in clinical well-being, and shortening of the disease duration. Patients treated with BSS had a significant reduction in duration of hospital stay (6.9 days) compared with placebo-treated patients (8.5 days). Also, intravenous fluid requirements decreased significantly more rapidly and to a greater degree in the BSS-treated group. Bismuth subsalicylate was associated with clearance of pathogenic Escherichia coli from the stools in 100% of cases but was not different from placebo in rotavirus elimination. Bismuth subsalicylate was well tolerated with no reported adverse effects. Blood bismuth and serum salicylate levels were well below levels considered toxic. In this study, BSS provided effective adjunctive therapy for acute diarrhea, allowing children to get well sooner with less demand on the nursing and hospital staff.

[Cutaneous response to 2 and 10 units of tuberculin in infants]. / Respuesta cutánea de lactantes a 2 y 10 unidades de tuberculina.

A study was done in 322 healthy, well nourished infants, 3 to 18 months old from day care centers of metropolitan Santiago, Chile, that were given BCG immunization in their neonatal period: 304 (94.4%) of them showed BCG scars and were included in a double blind open study, to determine the cutaneous responses to 2 TU and 10 TU tuberculin (PPD). There were no differences in the mean size of cutaneous reactions nor in percent positive responses (greater than or equal to 10 mm), but cutaneous reactions greater than or equal to 15 mm were more frequent in infants tested with PPD 10 TU. In 184 out of 304 infants (60.5%) tuberculin reactions were negative (less than or equal to 10 mm). Eighteen out of 322 infants (5.6%) that didn't show BCG scars were injected with PPD 2 TU: tuberculin reactions sized 6 to 9 mm were recorded in 3/18 of these infants but none of them attained 10 mm. Fifty five infants whose tuberculin reactions were 5 mm or less were retested: a booster effect was likely from the appearance of enhanced dermal response after a second tuberculin test done with the same or higher tuberculin strength than the first one in 12/47 of these infants with BCG scar (25%) and in only 1/8 such subjects without BCG scar.

Use of bismuth subsalicylate in acute diarrhea in children.

Results of a pilot study suggest that bismuth subsalicylate (BSS) favorably altered the course of rotavirus-associated diarrhea in children. This was more evident in those who also had a bacterial pathogen. Subsequently, 123 infants and children with acute diarrhea were admitted to a randomized, parallel, double-blind, placebo-controlled clinical trial. Patients received either BSS at a dosage of 100 mg/(kg.d) for 5 days or a placebo. Patients in the two groups were comparable with respect to age, sex, weight, height, and baseline disease parameters. Compared with subjects treated with placebo, those who received BSS had significantly lower stool weight sooner; improved stool consistency sooner; shorter hospital stay; lower number of stools; decreased need for intravenous fluids; and better evolution of clinical condition. The maximum mean serum level of salicylate occurred on day 3, and the mean blood level of bismuth on the last day of dosing (day 5) was 5.8 ppb.

[Pathogenic agents in acute non-enterocolic diarrheal syndrome]. / Agentes patógenos en el síndrome diarreico agudo no enterocólico.

Along a one year period 112 infants admitted with non enterocolic acute diarrhea were studied for isolation of potentially ethiologic agents, namely enteropathogenic bacteria (Salmonella, Shigella, Campylobacter, classic enteropathogenic, enteroinvasive and enterotoxigenic Escherichia coli), Rotavirus (viral RNA electrophoresis) and enteroparasites (Telemann and PAFS). The most frequently identified pathogen was rotavirus (57.8%), followed by thermo labile toxin producing Escherichia coli (19.7%). The frequency of classic enteropathogenic Escherichia coli was 13.9%, that of thermo stable toxin producing Escherichia coli 5.7%, Shigella 4.1%, Campylobacter 3.3% and Salmonella 1.6%. Bacteriae were isolated from 40.2%, of patients, predominantly in summer. Enteroparasites were detected in 13.1% of the cases, Entamoeba histolytica being the most frequent. In 32.8% of the cases more than one pathogen was isolated.