J Infect Dis

The prognostic relevance of the nonstructural 5A gene interferon sensitivity determining region is different in infections with genotype 1b and 3a isolates of hepatitis C virus.

Year 1998
Saiz JC. Lopez-Labrador FX. Ampurdanes S. Dopazo J. Forns X. Sanchez-Tapias JM. Rodes J.
Hospital Clinic, Department of Medicine, Facultad de Medicina, Universidad de Barcelona, Spain. JCSAIZ@medicina.ub.es
Hepatitis C virus (HCV) RNA serum concentration, quasispecies complexity, and sequence and phylogenetic analysis of the nonstructural 5A gene (NS5A) interferon sensitivity determining region (ISDR) were determined in pretreatment serum samples from 47 patients with chronic hepatitis C (36 infected by HCV genotype 1b and 11 by 3a). Among HCV genotype 1b-infected patients, virus load was lower (P = .003) and the number of NS5A-ISDR amino acid changes was higher (P = .001) in long-term responders than in non-long-term responders, but there were no differences in quasispecies complexity. Multivariate analysis showed a close association between response to interferon and NS5A-ISDR phenotype. Phylogenetic analysis showed that isolates from non-long-term responders clustered apart from the majority of isolates from long-term responders. There was no association between virologic features and therapeutic response in HCV genotype 3a-infected patients. In conclusion, low virus load and mutant NS5A-ISDR phenotype are closely associated with long-term response to interferon in HCV genotype 1b- but probably not in 3a-infected patients.

Virulence and colonization-associated properties of Helicobacter pylori isolated from children and adolescents.

Celik J. Su B. Tiren U. Finkel Y. Thoresson AC. Engstrand L. Sandstedt B. Bernander S. Normark S.
Swedish Institute of Infectious Disease Control, and Department of Women and Child Health, St. Goran's Children's Hospital, Stockholm.
Helicobacter pylori isolates from 32 children and adolescents were characterized with respect to putative virulence and colonization-associated properties. Only 3 of the subjects had duodenal ulcer. All but 2 of the remaining 29 had various degrees of chronic gastric inflammation. No significant correlation between degree of inflammation and presence of the cag-pathogenicity island, cytotoxin production, vacA alleles associated with cytotoxin expression, and binding ability to the Lewis(b) (Le[b]) oligosaccharide was found. Only 4 isolates expressed the Le(b)-specific adhesin, of which 3 were also cag region-positive. This is in contrast to adults with gastritis or peptic ulcer disease (or both), in whom most of the H. pylori isolates bind Le(b). In an in situ binding assay H. pylori were less able to adhere to gastric surface mucous cells in biopsies taken from children compared with adults, suggesting a lower expression of the Le(b) oligosaccharide in the children.

Enteroaggregative Escherichia coli produce intestinal inflammation and growth impairment and cause interleukin-8 release from intestinal epithelial cells.

Steiner TS. Lima AA. Nataro JP. Guerrant RL.
Division of Geographic and International Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Enteroaggregative E. coli (EAggEC) are emerging as an important cause of persistent diarrhea, especially in children in the developing world, yet the pathogenesis of EAggEC infection is poorly understood. In an ongoing prospective study of childhood diarrhea in an urban Brazilian slum, EAggEC are the leading cause of persistent diarrhea. Children from this study with EAggEC and persistent diarrhea had significant elevations in fecal lactoferrin, interleukin (IL)-8, and IL-1beta. Moreover, children with EAggEC without diarrhea had elevated fecal lactoferrin and IL-1beta concentrations. The children with EAggEC in their stool had significant growth impairment after their positive culture, regardless of the presence or absence of diarrhea. Finally, 2 EAggEC strains were shown to cause IL-8 release from Caco-2 cells, apparently via a novel heat-stable, high-molecular-weight protein. These findings suggest that EAggEC may contribute to childhood malnutrition, trigger intestinal inflammation in vivo, and induce IL-8 secretion in vitro.

Hospitalizations associated with rotavirus diarrhea in the United States, 1993 through 1995: surveillance based on the new ICD-9-CM rotavirus-specific diagnostic code.

Parashar UD. Holman RC. Clarke MJ. Bresee JS. Glass RI.
Epidemic Intelligence Service, Epidemiology Program Office, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. UAP2@CDC.GOV
The introduction of a specific International Classification of Diseases code for rotavirus diarrhea in 1992 prompted examination of the National Hospital Discharge Survey (NHDS) for trends in rotavirus-associated hospitalizations among US children aged 1 month through 4 years. During 1993-1995, 13.5% of hospitalizations were associated with diarrhea (n = 162,478/year). Rotavirus was the most common pathogen identified, coded in 16.5% of diarrhea cases (n = 26,798/year), and increased from 13.3% in 1993 to 18.9% in 1995. The age distribution and seasonality of hospitalizations of presumed noninfectious and viral etiology resembled those associated with rotavirus. Rotavirus was reported as a cause of diarrhea more frequently by hospitals that were large (> or =100 beds), proprietary-owned, or in the West/Midwest. Although these findings suggest incomplete detection of rotavirus diarrhea cases, the large number of rotavirus-associated hospitalizations underscores the need for vaccines and indicates that NHDS data could be used to monitor the impact of a US rotavirus immunization program.

Association of antibody to GB virus C (hepatitis G virus) with viral clearance and protection from reinfection.

Year 1998
Thomas DL. Vlahov D. Alter HJ. Hunt JC. Marshall R. Astemborski J. Nelson KE.
Division of Infectious Diseases, Johns Hopkins Medical School, Baltimore, Maryland, USA.
GB virus C (GBV-C) RNA and envelope antibody were assessed in a median of 4 samples collected over 6.5 years among injection drug users (IDUs). A marker of GBV-C infection was detected in 110 (94.8%) of 116 IDUs. GBV-C RNA was detected at all visits in 32, was never detected in 70, was acquired in 7, and was cleared in 8. The odds of detecting anti-GBV-C were 103-fold higher in participants without detectable RNA (64 of 70) than in IDUs with persistent RNA (3 of 32; P < 10(-7)). Anti-GBV-C was detected in all 8 instances of RNA clearance. GBV-C RNA never reappeared once it was cleared, and there were no new GBV-C infections among 61 anti-GBV-C-positive IDUs observed for 382 person-years, though all had ongoing drug use. Studies using RNA testing alone may significantly underestimate the occurrence of GBV-C infection. Anti-GBV-C is highly associated with viral clearance and protection from reinfection.

Milk immunoglobulin with specific activity against purified colonization factor antigens can protect against oral challenge with enterotoxigenic Escherichia coli.

Year 1998
Freedman DJ. Tacket CO. Delehanty A. Maneval DR. Nataro J. Crabb JH.
ImmuCell Corp., Portland, Maine 04103, USA.
Enterotoxigenic Escherichia coli (ETEC) is the most commonly isolated pathogen responsible for travelers' diarrhea and the cause of up to 650 million cases of pediatric diarrhea per year in the developing world. As a safe alternative to the prophylactic use of antibiotics, a hyperimmune bovine milk antibody product with specific activity against purified colonization factor antigens (CFAs) was developed and evaluated in a human challenge study. Twenty-five healthy adult volunteers were challenged orally with 10(9) cfu of a virulent CFA/I-bearing ETEC. In the randomized double-blind trial, 7 of 10 volunteers receiving a lactose-free placebo developed clinical diarrhea after challenge, compared with only 1 of 15 cases in volunteers receiving active product (Fisher's exact test, P < .0017). It is concluded that antibodies against CFAs alone are sufficient for protection and that prophylaxis with milk-derived immunoglobulin is a feasible alternative to existing drug interventions.

Delayed treatment with recombinant human tissue factor pathway inhibitor improves survival in rabbits with gram-negative peritonitis.

Year 1998
Camerota AJ. Creasey AA. Patla V. Larkin VA. Fink MP.
Department of Anesthesia, Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
To determine whether treatment with recombinant human tissue factor pathway inhibitor (TFPI), an inhibitor of the extrinsic coagulation pathway, can improve survival in a clinically relevant model of gram-negative sepsis, rabbits were given an intraperitoneal inoculation of a suspension containing hemoglobin (40 microg/mL), porcine mucin (150 microg/mL), and viable Escherichia coli O18:K1 (1.0 +/- 0.5 x 10(5) cfu/kg). Treatment with gentamicin (5 mg/kg every 12 h for five doses) was instituted 4 h after induction of peritonitis. At the same time point, rabbits were randomized to receive a 24-h infusion of vehicle or one of three different doses of TFPI. Treatment groups, 7-day survival rates, and significance versus control were as follows: control, 1 of 20; TFPI(LOW DOSE) (0.1 mg/kg, then 1 microg/kg/min), 3 of 12 (P = .14); TFPI(MID DOSE), (0.5 mg/kg, then 5 microg/kg/min), 7 of 12 (P = .002); TFPI(HIGH DOSE) (10 mg/kg, then 10 microg/kg/min), 4 of 13 (P = .04). Thus, delayed treatment with TFPI improves survival in septic rabbits.

Cryptosporidiosis in northeastern Brazilian children: association with increased diarrhea morbidity.

Year 1998
Agnew DG. Lima AA. Newman RD. Wuhib T. Moore RD. Guerrant RL. Sears CL.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
To evaluate the impact of Cryptosporidium infection on diarrheal disease burden and nutrition status, a nested case-control study was done among children who were followed from birth in Fortaleza, Brazil. The diarrhea history and growth records of 43 children with a symptomatic diarrhea episode of cryptosporidiosis (case-children) were compared with those of 43 age-matched controls with no history of cryptosporidiosis. After Cryptosporidium infection, case-children < or = 1 year old experienced an excessive and protracted (nearly 2 years) diarrheal disease burden. Case-children < or = 1 year old with no history of diarrhea prior to their Cryptosporidium infection also experienced a subsequent increased diarrheal disease burden with an associated decline in growth. Control subjects experienced no change in their diarrhea burden over time. This study suggests that an episode of symptomatic Cryptosporidium infection in children < or = 1 year of age is a marker for increased diarrhea morbidity.

Impact of treatment with human immunodeficiency virus (HIV) protease inhibitors on hepatitis C viremia in patients coinfected with HIV.

Year 1998
Rutschmann OT. Negro F. Hirschel B. Hadengue A. Anwar D. Perrin LH.
Division of Infectious Diseases and of Gastroenterology, University Hospital, Geneva, Switzerland. Rutschma@dminov1.hcuge.ch
The impact of human immunodeficiency virus (HIV) protease inhibitors on hepatitis C (HCV) viremia was assessed in 19 patients infected with both HIV and HCV. HIV and HCV RNA levels were measured before and during treatment with protease inhibitors. Before treatment, mean levels of HCV RNA were 5.3 log for HCV RNA and 5.0 log for HIV RNA. CD4 lymphocyte counts were 63/mm3. After 6 weeks of treatment, a mean reduction of 2.1 log10 in HIV RNA (P < .001) and a mean (+/-SE) increase of 73 (+/-21) CD4 and 296 (+/-70) CD8 cells were observed (P < .05). In contrast, both HCV viremia (+0.4 log +/- 0.1) and alanine aminotransferase increased (P < .04). HCV RNA levels returned to baseline after 17 and 32 weeks of treatment. Thus, potent anti-HIV regimens with protease inhibitors may temporarily worsen HCV status despite improvement of HIV parameters.

Absence of hepatitis C virus and detection of hepatitis G virus/GB virus C RNA sequences in the semen of infected men.

Year 1998
Semprini AE. Persico T. Thiers V. Oneta M. Tuveri R. Serafini P. Boschini A. Giuntelli S. Pardi G. Brechot C.
Department of Obstetrics and Gynecology, San Paolo Biomedical Institute, University of Milan Medical School, Italy. reprodun@tin.it
The identification of hepatitis C virus (HCV) in semen remains controversial and that of hepatitis G virus (HGV) or GB virus C (GBV-C) has never been investigated. Serum and semen from 90 anti-HCV-positive drug users were tested (27 infected with HIV) for HCV and HGV/GBV-C RNAs by polymerase chain reaction (PCR) assay, hybridization, and sequence analysis. Semen was processed into round cells, seminal plasma, and spermatozoa. Fifty-six patients were HCV-viremic, but HCV-RNA was not identified in their seminal fractions. However, PCR inhibitors were found in the semen of 34 of these men. Twenty-eight patients had HGV/GBV-C RNA in their blood and for 24 of them, ejaculates were available for analysis. HGV/GBV-C RNA was found in the seminal plasma of 6 of 12 samples free from PCR inhibitors. These results agree with the low risk of sexual transfer of HCV and provide preliminary evidence for the presence of HGV/GBV-C in semen.

Pathogen transmission in child care settings studied by using a cauliflower virus DNA as a surrogate marker.

Year 1998
Jiang X. Dai X. Goldblatt S. Buescher C. Cusack TM. Matson DO. Pickering LK.
Center for Pediatric Research, Children's Hospital of The King's Daughters, Eastern Virginia Medical School, Norfolk 23510-1001, USA. jjiang@chkd.com
Two regions of cauliflower mosaic virus DNA were designed as markers to study pathogen transmission in a child care home (CCH) and child care center (CCC) and in homes of CCC children. The DNA markers were stable for 1 month in the environment. The DNA markers were introduced into the environment through sensitized objects, and spread in the environment was traced by detection of the markers with polymerase chain reaction. The DNA markers spread rapidly in both the CCH and CCC after introduction and spread more rapidly in the toddler room than in the infant room of the CCC. Hand touching of contaminated areas was the major factor leading to spread of the markers. Hand washing and surface wiping decreased spread of the markers. The markers spread minimally from room to room in the CCC but were detected in the children's homes after introduction of markers in the CCC.

A nationwide case-control study of Escherichia coli O157:H7 infection in the United States.

Year 1998
Slutsker L. Ries AA. Maloney K. Wells JG. Greene KD. Griffin PM.
Foodborne and Diarrheal Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. lms5@cdc.gov
Risk factors for Escherichia coli O157:H7 infection were investigated in a case-control study at 10 medical centers throughout the United States. Among 73 case-patients and 142 matched controls, exposures in the 7 days before illness associated with E. coli O157:H7 infection in univariate analysis included consumption of hamburger (matched odds ratio [MOR], 3.8; 95% confidence interval [CI], 1.9-7.9), undercooked hamburger (MOR, 4.5; 95% CI, 1.6-12.2), or hot dogs (MOR, 2.2; 95% CI, 1.1-4.4); eating at a fast-food restaurant (MOR, 2.3; 95% CI, 1.1-4.6); drinking unchlorinated well water (MOR, 2.4; 95% CI, 1.1-5.7); swimming in a pond (MOR, 5.4; 95% CI, 1.1-26.0); and having a household member with diarrhea (MOR, 11.9; 95% CI, 2.7-53.5). In multivariate analysis, only eating undercooked hamburger remained associated with infection. Seven (8%) of 93 patients developed hemolytic uremic syndrome and 1 died. Prevention strategies aimed at modifying risk factors may help to reduce the risk of infection with E. coli O157:H7.

Persistent infection with small colony variant strains of Staphylococcus aureus in patients with cystic fibrosis.

Year 1998
Kahl B. Herrmann M. Everding AS. Koch HG. Becker K. Harms E. Proctor RA. Peters G.
Institute of Medical Microbiology and Department of Pediatrics, University of Muenster Hospital and Clinics, Germany.
In a 34-month prospective study to determine the prevalence of Staphylococcus aureus small colony variants (SCVs) in cystic fibrosis (CF) patients, S. aureus SCVs or SCVs plus normal S. aureus were recovered from 26 of 78 patients; 27 patients harbored only normal S. aureus. By pulsed-field gel electrophoresis, clonal identity was demonstrated of SCV and normal strains isolated at the same time and of multiple S. aureus SCV and normal strains in consecutive specimens from individual patients. All S. aureus SCVs were resistant to antifolate antibiotics, while the corresponding parent strains were susceptible, and in 11 of 12 SCV/normal pairs, gentamicin was less active against S. aureus with the SCV phenotype than against the normal isolate. Analysis of the underlying auxotrophism of SCVs revealed hemin, thymidine, and/or menadione dependencies. Thus, S. aureus SCVs are highly prevalent in respiratory secretions of CF patients, persist over extended periods, and may contribute to S. aureus persistence in CF patients.

An outbreak of Brainerd diarrhea among travelers to the Galapagos Islands.

Year 1998
Mintz ED. Weber JT. Guris D. Puhr N. Wells JG. Yashuk JC. Curtis M. Tauxe RV.
Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. edm1@cdc.gov
In 1992, an outbreak of chronic diarrhea occurred among passengers on a cruise ship visiting the Galapagos Islands, Ecuador. Passengers (548) were surveyed, and stool and biopsy specimens from a sample who reported chronic diarrhea were examined. On completed questionnaires, returned by 394 passengers (72%), 58 (15%) reported having chronic diarrhea associated with urgency (84%), weight loss (77%), fatigue (71%), and fecal incontinence (62%). Illness began 11 days (median) after boarding the ship and lasted 7 to >42 months. Macroscopic and histologic abnormalities of the colon were common, but extensive laboratory examination revealed no etiologic agent. No one responded to antimicrobial therapy. Patients were more likely than well passengers to have drunk the ship's unbottled water or ice before onset of illness and to have eaten raw sliced fruits and vegetables washed in unbottled water. Water handling and chlorination on the ship were deficient. Outbreaks of a similar illness, Brainerd diarrhea, have been reported in the United States. Although its etiology remains unknown, Brainerd diarrhea may also occur among travelers.

The individual and joint contributions of Helicobacter pylori infection and family history to the risk for peptic ulcer disease.

Year 1998
Brenner H. Rothenbacher D. Bode G. Adler G.
Department of Epidemiology, University of Ulm, Germany.
Family history of peptic ulcer and infection with Helicobacter pylori have been identified as major risk factors for peptic ulcer disease. It is unclear, however, to what degree their impacts are independent of each other. This question was addressed in a cross-sectional study among 299 consecutive out-patients (25-54 years old) of a general practitioner. Adjusted odds ratios (95% confidence intervals) for gastroscopically verified peptic ulcer disease were 3.8 (1.4-10.1) for persons with H. pylori infection, 8.4 (2.9-24.1) for persons with a family history of ulcer, and 29.5 (6.1-143.9) for persons with both risk factors compared with persons without these risk factors. These results suggest strong, multiplicative contributions of both factors to the risk for peptic ulcer disease.

Neonatal fulminant hepatitis B: structural and functional analysis of complete hepatitis B virus genomes from mother and infant.

Year 1998
Sterneck M. Kalinina T. Otto S. Gunther S. Fischer L. Burdelski M. Greten H. Broelsch CE. Will H.
Department of Medicine, Surgery, and Pediatrics, University Hospital Eppendorf, Hamburg, Germany. sterneck@uke.uni-hamburg.de
Transmission of hepatitis B virus (HBV) from anti-hepatitis B e (anti-HBe)-positive carrier mothers to their infants may result in neonatal fulminant hepatitis B (FHB). We investigated whether HBV variants with a particular DNA sequence and functional phenotype, responsible for FHB, are selected during transmission. Full-length HBV genomes from a mother-infant pair were completely sequenced and transfected into human hepatoma cells. The dominant neonatal and maternal HBV populations were nearly identical (homology 99.8%) and showed a precore stop codon mutation, T-1762 and A-1764 substitutions in the core promoter region, and pre-S2 start codon mutations. Cells transfected with variants from mother and child, compared with wild-type virus, synthesized and released a similar number or fewer HBV DNA-containing particles. In conclusion, no particular HBV strain emerged during neonatal FHB. In this case, a de novo infection with variants showing a defect in HBe antigen and pre-S2 protein synthesis but not a high replication competence probably contributed to the fulminant disease course.

Identification of more than one mutation in the hepatitis B virus polymerase gene arising during prolonged lamivudine treatment.

Year 1998
Niesters HG. Honkoop P. Haagsma EB. de Man RA. Schalm SW. Osterhaus AD.
Department of Gastroenterology, University Hospital Rotterdam, The Netherlands. niesters@viro.fgg.eur.nl
Lamivudine has been shown to be a potent and nontoxic inhibitor of hepatitis B virus (HBV) replication in chronically infected patients. During prolonged treatment, drug resistance may develop, related to a mutation of Met to Val or Ile in the YM552DD motif of the HBV DNA polymerase gene. Analysis of the HBV DNA polymerase gene from 8 chronic hepatitis B patients with suspected resistance to lamivudine showed that in addition to a mutation in the YM552DD motif, a second mutation located in the B domain of this gene, a Leu528-to-Met528 change, was consistently and exclusively found in 4 patients showing the YV552DD motif. This suggests a functional or structural relationship between these domains. Since the presence of both the YI552DD and YV552DD motif sometimes preceded the exclusive presence of the YV552DD motif, we conclude that the YI552DD motif could occur as a temporal intermediate. After cessation of therapy, the wild type sequences reemerged.

A prolonged outbreak of Shigella sonnei infections in traditionally observant Jewish communities in North America caused by a molecularly distinct bacterial subtype.

Year 1998
Sobel J. Cameron DN. Ismail J. Strockbine N. Williams M. Diaz PS. Westley B. Rittmann M. DiCristina J. Ragazzoni H. Tauxe RV. Mintz ED.
Foodborne and Diarrheal Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. qzs32@cdc.gov
During 1994-1996, Shigella sonnei outbreaks occurred in 8 North American traditionally observant Jewish communities. These communities remain relatively separate from neighboring populations while maintaining close contact by travel with coreligionists in other cities. Epidemiologic investigations suggested community-to-community transmission via travel. Outbreak-related and control isolates of S. sonnei from each city were subtyped by pulsed-field gel electrophoresis (PFGE) to confirm an epidemiologic linkage between outbreaks. Forty-three (94%) of 46 outbreak-related isolates had closely related PFGE patterns, constituting a single subtype; 33 (94%) of 35 control isolates demonstrated unrelated PFGE patterns. Several patterns differing by < or = 3 bands were identified within the outbreak subtype; one of these accounted for 65% of outbreak isolates. Hence, a single subtype of S. sonnei caused an international outbreak involving 8 traditionally observant Jewish communities, but not neighboring populations, over a 2-year period, suggesting sustained propagation of the epidemic strain between communities.

Enteroaggregative Escherichia coli strains as a cause of travelers diarrhea: a case-control study.

Year 1998
Gascon J. Vargas M. Quinto L. Corachan M. Jimenez de Anta MT. Vila J.
Servei Microbiologia i Parasitologia, Unitat Epidemiologia, Hospital Clinic, University of Barcelona, School of Medicine, Spain.
To elucidate the importance of enteroaggregative Escherichia coli (EAggEC) strains as a cause of traveler's diarrhea in Spanish travelers, a prospective case-control 1:1 study was done in a university hospital clinic for travelers. EAggEC strains were isolated from 23 of 165 case-patients and from 4 of 165 controls (P = .0003). In 16 patients, this was the only isolate recovered. Six of the EAggEC-positive isolates from the case-patients and 2 from the controls were positive for the enteroaggregative stable toxin type 1 gene. Other enteropathogens were also isolated. Shigella and enterotoxigenic E. coli strains showed significant differences between cases and controls (P = .0023 and P < .0001, respectively). Geographic distribution of the EAggEC strains was homogeneous, and the clinical symptom, secretory diarrhea, did not differ statistically with that for the enterotoxigenic E. coli strains. EAggEC strains are a cause of secretory diarrhea in Spaniards traveling to developing countries.

Chemotactic factors in bronchial secretions of cystic fibrosis patients.

Year 1998
Dayer Pastore F. Schlegel-Haueter SE. Belli DC. Rochat T. Dudez TS. Suter S.
Department of Pediatrics and Pulmonary Division of the Department of Medicine, University Hospitals of Geneva, Switzerland. Fabienne.Dayer@hcuge.ch
To understand chronic neutrophil attraction into cystic fibrosis airways, both global chemotactic activity and individual chemotactic factors were studied in bronchial secretions. Bronchial secretions of 8 cystic fibrosis patients, collected on the first day of admission for antibiotic treatment, showed a high chemotactic index (19.4 +/- 5.7, n = 8). Fractionation by gel filtration of bronchial secretions resulted in three chemotactic fractions. The first factor corresponded to interleukin-8, and the second activated neutrophils via the FMLP receptor. The third factor, which was of lower molecular weight, did not activate FMLP or leukotriene B4 receptors, and its nature is still under investigation. Treating patients with antibiotics reduced global chemotactic activity, mainly by reducing the activity due to stimulation of the FMLP receptor.

Direct isolation of DNA from patient stools for polymerase chain reaction detection of Cryptosporidium parvum.

Year 1998
Zhu G. Marchewka MJ. Ennis JG. Keithly JS.
Wadsworth Center, New York State Department of Health, Albany 12208, USA.
Although polymerase chain reaction (PCR) can sensitively detect parasitic or other infections, its use with fecal samples is extremely limited, primarily because of the presence of substances that inhibit DNA extension. Here an improved protocol is reported for directly isolating DNA from aged or fresh formalin-fixed stools, which can then be used to detect Cryptosporidium parvum by nested PCR. This method is highly reproducible, sensitive, and specific. It detects

Dynamics of hepatitis C viremia following interferon-alpha administration.

Year 1998
Yasui K. Okanoue T. Murakami Y. Itoh Y. Minami M. Sakamoto S. Sakamoto M. Nishioji K.
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Knowledge of the dynamics of hepatitis C virus (HCV) in vivo is important for elucidation of its pathogenesis and the establishment of therapeutic guidelines. The aim of this study was to obtain kinetic information about virus load following interferon-alpha (IFN-alpha) administration. Serial serum HCV core protein and HCV RNA levels were measured. IFN-alpha exponentially reduced serum HCV levels. The mean (+/-SD) viral half-life was 7.0 +/- 2.6 h in HCV core protein assay and 7.2 +/- 3.1 h in HCV RNA assay on the first day of therapy. This initial rapid decrease was followed by a slower decrease in serum HCV levels thereafter. Thus, the biphasic reduction in virus load during IFN-alpha therapy was demonstrated.

Perinatal transmission of hepatitis C virus from human immunodeficiency virus type 1-infected mothers. Women and Infants Transmission Study.

Year 1998
Thomas DL. Villano SA. Riester KA. Hershow R. Mofenson LM. Landesman SH. Hollinger FB. Davenny K. Riley L. Diaz C. Tang HB. Quinn TC.
Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Antepartum plasma hepatitis C virus (HCV) RNA was quantified in 155 mothers coinfected with HCV and human immunodeficiency virus type 1 (HIV-1), and HCV RNA was serially assessed in their infants. Of 155 singleton infants born to HCV antibody-positive mothers, 13 (8.4%) were HCV infected. The risk of HCV infection was 3.2-fold greater in HIV-1-infected infants compared with HIV-1-uninfected infants (17.1% of 41 vs. 5.4% of 112, P = .04). The median concentration of plasma HCV RNA was higher among the 13 mothers with HCV-infected infants (2.0 x 10(6) copies/mL) than among the 142 mothers with HCV-negative infants (3.5 x 10(5) copies/mL; P < .001), and there were no instances of HCV transmission from 40 mothers with HCV RNA concentrations of < 10(5) copies/mL. Women dually infected with HIV-1 and HCV but with little or no detectable HCV RNA should be reassured that the risk of perinatal transmission of HCV is exceedingly low.

Enteric infections in an endemic area induce a circulating antibody-secreting cell response with homing potentials to both mucosal and systemic tissues.

Year 1998
Qadri F. Makela PH. Holmgren J. Albert MJ. Mannoor K. Kantele A. Saha D. Salam MA. Kantele JM.
International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka.
Enteric infections induce a response of circulating pathogen-specific antibody-secreting cells (ASC). The expression of homing receptors (HRs) on these cells was studied in patients with diarrhea caused by Vibrio cholerae in Bangladesh, an area in which cholera is endemic. The gut HR, alpha4beta7, was expressed by approximately 80% of the ASC, indicating mucosal homing of these cells. However, the peripheral lymph node HR, L-selectin, was also expressed by approximately 80% of the ASC specific to either cholera toxin or O antigen. In earlier findings after oral immunization in nonendemic areas, alpha4beta7 has been expressed by approximately 100% and L-selectin by approximately 50% of the ASC. In comparison, the present data speak for a more systemic targeting of the immune response associated with long-lasting immunity in an endemic area. The results thus provide insight for the continued development and evaluation of vaccines.

Glycine-valine dimorphism at the 86th amino acid of HLA-DRB1 influenced the prognosis of postschistosomal hepatic fibrosis.

Year 1998
Hirayama K. Chen H. Kikuchi M. Yin T. Itoh M. Gu X. Zhang S. Yuan H.
Department of Medical Zoology, Saitama Medical School, Moroyama, Japan. hiraken@saitama-med.ac.jp
Chinese patients (n = 113) with schistosomal hepatic fibrosis diagnosed by ultrasonography (grade I, II, or III) and 184 age- and sex-matched persons with no clinical information of schistosomal infection were typed for their HLA-DRB1 alleles by DNA typing. There was no single allele that conferred susceptibility or resistance to fibrosis. However, there were three groups of alleles that showed decreased (resistant), increased (susceptible), or neutral frequency in the patients with fibrosis. The susceptible alleles, DRBI *1202, DRB1 *1404, and DRBI *1405, shared a valine at amino acid residue 86, whereas the resistant alleles, DRB1*11011, DRB1*0409, and DRB1*0701, all had glycine at position 86. Therefore, this study focused on the glycine-valine dimorphism at aa 86, which influences the depth of the P1 pocket in the antigen binding groove, and found that the 86th valine allele was significantly increased in the patients with fibrosis (odds ratio = 2.2; 95% CI = 1.34-3.61, corrected P < .05).

GB virus C infection in patients with primary antibody deficiency.

Year 1998
Morris A. Webster AD. Brown D. Harrison TJ. Dusheiko G.
Department of Clinical Immunology, Medical Research Council Immunodeficiency Clinic, Royal Free Hospital, London, United Kingdom.
Sera from 77 patients with common variable immunodeficiency (CVID) were tested for GB virus C (GBV-C) RNA, because they are prone to unexplained chronic hepatitis, and from 28 patients with X-linked agammaglobulinemia (XLA) who have a similar primary antibody deficiency but are not prone to hepatitis. Eight CVID and 8 XLA patients were positive; 6 positive CVID and 3 XLA patients had abnormal liver enzymes, explained in 3 by either hepatitis B or C virus infection. Most patients tested had antibodies to the E2 antigen of GBV-C, apparently passively acquired from their immunoglobulin therapy. The high prevalence of GBV-C viremia in CVID and XLA patients is probably explained by their long-term exposure to blood products. Our data indicate that GBV-C does not cause chronic hepatitis in immunocompromised XLA patients and is not the cause of chronic non-B or -C hepatitis in the majority of CVID patients.

GB virus C/hepatitis G virus infection: a favorable prognostic factor in human immunodeficiency virus-infected patients?

Year 1998
Heringlake S. Ockenga J. Tillmann HL. Trautwein C. Meissner D. Stoll M. Hunt J. Jou C. Solomon N. Schmidt RE. Manns MP.
Department of Gastroenterology, Medizinische Hochschule, Hannover, Germany.
To investigate a possible influence of GB virus C (GBV-C) in immunocompromised patients, the prevalences of GBV-C RNA and anti-E2 antibody in 197 human immunodeficiency virus (HIV)-infected patients and in 120 control blood donors were studied. GBV-C RNA was detected in 33 of 197 HIV-infected patients (16.8%) compared with 1 in 120 blood donors (0.8%) (P < .001). Previous exposure to GBV-C (anti-E2 antibody-positive) was shown in 56.8% of HIV patients and in 9% of blood donors. GBV-C viremia was not associated with hepatitis. Despite approximately equal duration of HIV infection in all subgroups, the CD4 cell counts were significantly higher in GBV-C-viremic patients (344 cells/microL) compared with exposed (259 cells/microL) and unexposed (170 cells/microL) patients (P = .017 and P < .001). Furthermore, Kaplan-Meier analysis demonstrated significantly better cumulative survival in GBV-C RNA-positive HIV-infected patients, suggesting that GBV-C might be a favorable prognostic factor in HIV disease.

Mother-to-infant transmission of GB virus C/hepatitis G virus: the role of high-titered maternal viremia and mode of delivery.

Year 1998
Lin HH. Kao JH. Yeh KY. Liu DP. Chang MH. Chen PJ. Chen DS.
Department of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei.
To study mother-to-infant transmission of GB virus C/hepatitis G virus (GBV-C/HGV), blood samples of infants born to carrier mothers were collected beginning 3 months after birth and were tested for GBV-C/HGV RNA until 1 year of age. Of 2046 mothers, 2.1% were positive for GBV-C/HGV RNA, and 25 of their infants were followed for a median of 12 months. Thirteen infants (52%) were viremic, and infection became persistent in all. Maternal GBV-C/HGV RNA levels of this group were >10(7) copies/mL. Nucleotide sequence comparison in 5 viremic mother-infant pairs revealed a homology of 93%-98.2%, and none delivered by elective cesarean section. In comparison, of the 12 uninfected infants' mothers, 10 had lower GBV-C/HGV RNA levels (mean, 5 x 10(4) copies/mL), and the remaining 2 high-titered mothers had elective cesarean section. Thus, high-titered maternal viremia and mode of delivery are closely associated with the mother-to-infant transmission of GBV-C/HGV to infants, and the infection usually becomes persistent.