ABSTRACT
BACKGROUND: Schistosomiasis caused by Schistosoma mansoni (Sm) is a chronic, debilitating and potentially deadly neglected tropical disease. The licensure of a vaccine to prevent schistosomiasis would represent a major breakthrough in public health. METHODS: The safety and immunogenicity of a candidate Sm vaccine were assessed in this phase I, double-blind, dose-escalation trial. Seventy-two healthy Sm-naïve 18-50â¯year olds were randomized to receive 3 doses â¼â¯8â¯weeks apart of saline placebo, or 10⯵g, 30⯵g, or 100⯵g of recombinant Sm-Tetraspanin-2 vaccine formulated on aluminum hydroxide adjuvant (Sm-TSP-2/Al) with or without 5⯵g of glucopyranosyl lipid A aqueous formulation (GLA-AF). Clinical and serologic responses were assessed for 1â¯year after dose 3. RESULTS: Vaccines were safe and well-tolerated. The most common reactions were injection site tenderness and pain, and headache and fatigue. Tenderness and pain were more frequent in groups receiving vaccine with GLA-AF than placebo (pâ¯=â¯0.0036 and pâ¯=â¯0.0014, respectively). Injection site reactions among those given Sm-TSP-2/Al with GLA-AF lasted 1.22 and 1.33â¯days longer than those receiving Sm-TSP-2/Al without GLA-AF or placebo (pâ¯<â¯0.001 for both). Dose- and adjuvant-related increases in serum IgG against Sm-TSP-2 were observed. Peak IgG levels occurred 14â¯days after dose 3. Seroresponse frequencies were low among recipients of Sm-TSP-2/Al without GLA-AF, but higher among subjects receiving 30⯵g or 100⯵g of Sm-TSP-2/Al with GLA-AF. More seroresponses were observed among those given 30⯵g or 100⯵g of Sm-TSP-2/Al with GLA-AF compared to placebo (pâ¯=â¯0.023 and pâ¯<â¯0.001, respectively). Seroresponse frequencies were 0%, 30%, 50%, and 89%, respectively, among those given placebo, or 10⯵g, 30⯵g or 100⯵g of Sm-TSP-2/Al with GLA-AF, suggesting a dose-response relationship for Sm-TSP-2/Al with GLA-AF (pâ¯=â¯0.0001). CONCLUSIONS: Sm-TSP-2/Al with or without GLA-AF was safe and well tolerated in a Sm-naïve population. A vaccine like the one under development may represent our best hope to eliminating this neglected tropical disease.
Subject(s)
Antibodies, Helminth/blood , Glucosides/immunology , Immunogenicity, Vaccine , Lipid A/immunology , Schistosomiasis/prevention & control , Vaccines/immunology , Adjuvants, Immunologic/administration & dosage , Adolescent , Adult , Animals , Antigens, Helminth/immunology , Cohort Studies , Cytokines/immunology , Dose-Response Relationship, Drug , Double-Blind Method , Female , Healthy Volunteers , Humans , Immunoglobulin G/blood , Male , Middle Aged , Schistosoma mansoni , Vaccines/adverse effects , Young AdultABSTRACT
Recent studies have suggested that among those receiving seasonal influenza vaccine (SIV), reduced immunogenicity is observed in recently vaccinated (RV; within the past season or 2) persons when compared with those not recently vaccinated (NRV). We performed a meta-analysis to assess the effect of recent immunization with SIV on serum H5 hemagglutination inhibition (HAI) antibody responses after influenza A/H5N1 vaccination using data from a series of randomized controlled trials. The primary outcome was seroconversion measured by HAI assays following receipt of 2 doses of H5N1 vaccine. The geometric mean titer (GMT) of serum HAI antibody after vaccination was the secondary outcome. Analyses were performed using propensity score (PS) matching. The PS for each individual in the meta-analysis cohort was calculated using logistic regression and covariates included age, gender, race, antigen dose, adjuvant, statin use and vaccine manufacturer. 2015 subjects enrolled in 7 clinical trials were eligible for inclusion in the meta-analysis cohort; among these, 915 (45%) were RV. 901 RV subjects were matched (1:1) with replacement to a subject who was NRV. Subjects who received SIV within the previous season were significantly less likely to seroconvert following H5N1 vaccination (adjusted odds ratio 0.76; 95%CI 0.60-0.96; pâ¯=â¯0.024), and the GMT was 18% higher among NRV subjects (GM ratio of HAI antibody 1.18; 95%CI 1.04-1.33; pâ¯=â¯0.008). Further work is needed to better define the effects of, and mechanisms contributing to, reduced immune responses to H5N1 vaccine among RV subjects.
Subject(s)
Antibodies, Viral/immunology , Influenza A Virus, H5N1 Subtype/immunology , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Seasons , Vaccination , Female , Humans , Immunogenicity, Vaccine , Male , Outcome Assessment, Health Care , Propensity ScoreABSTRACT
Case reports describe significant norovirus gastroenteritis morbidity in immunocompromised patients. We evaluated norovirus pathogenesis in prospectively enrolled solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with diarrhea who presented to Texas Children's Hospital and submitted stool for enteric testing. Noroviruses were detected by real-time reverse transcription polymerase chain reaction. Clinical outcomes of norovirus diarrhea and non-norovirus diarrhea patients, matched by transplanted organ type, were compared. Norovirus infection was identified in 25 (22%) of 116 patients, more frequently than other enteropathogens. Fifty percent of norovirus patients experienced diarrhea lasting ≥14 days, with median duration of 12.5 days (range 1-324 days); 29% developed diarrhea recurrence. Fifty-five percent of norovirus patients were hospitalized for diarrhea, with 27% requiring intensive care unit (ICU) admission. One HSCT recipient developed pneumatosis intestinalis. Three HSCT patients expired ≤6 months of norovirus diarrhea onset. Compared to non-norovirus diarrhea patients, norovirus patients experienced significantly more frequent ICU admission (27% vs. 0%, p = 0.02), greater serum creatinine rise (median 0.3 vs. 0.2 mg/dL, p = 0.01), and more weight loss (median 1.6 vs. 0.6 kg, p < 0.01). Noroviruses are an important cause of diarrhea in pediatric transplant patients and are associated with significant clinical complications.
Subject(s)
Caliciviridae Infections/virology , Diarrhea/virology , Hematopoietic Stem Cell Transplantation , Immunocompromised Host , Norovirus/isolation & purification , Organ Transplantation , Caliciviridae Infections/immunology , Child , Diarrhea/diagnosis , Diarrhea/epidemiology , Feces/chemistry , Feces/virology , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Survival , Humans , Male , Prognosis , Prospective Studies , RNA, Viral/genetics , Risk Factors , Texas/epidemiology , Transplant RecipientsABSTRACT
Erythrocyte binding antigen region II (EBA-175) is a conserved antigen of Plasmodium falciparum that is involved in binding of the parasite to the host's erythrocytes. We evaluated the safety and immunogenicity of a recombinant EBA-175 vaccine with aluminum phosphate adjuvant in healthy young adults living in the United States. Eighteen subjects/group received ascending doses (5, 20, 80, or 160 µg) of the vaccine at 0, 1, and 6 months; 8 subjects received placebo. Most of the injection site and systemic reactions were mild to moderate in intensity. After 2 or 3 doses of the vaccine at any concentration, antibody levels measured by enzyme-linked immunosorbent assay were significantly higher than those for the placebo group. Sera from subjects who received 3 doses of the vaccine at any concentration inhibited the growth of erythrocyte-stage P. falciparum at low levels compared to sera from placebo recipients or preimmune sera. In conclusion, the EBA-175 vaccine with adjuvant was safe and immunogenic in malaria-naïve subjects.
Subject(s)
Antigens, Protozoan/adverse effects , Antigens, Protozoan/immunology , Malaria Vaccines/adverse effects , Malaria Vaccines/immunology , Malaria, Falciparum/prevention & control , Protozoan Proteins/adverse effects , Protozoan Proteins/immunology , Adjuvants, Immunologic/administration & dosage , Adolescent , Adult , Aluminum Compounds/administration & dosage , Antibodies, Protozoan/blood , Antigens, Protozoan/administration & dosage , Enzyme-Linked Immunosorbent Assay , Female , Human Experimentation , Humans , Immunization, Secondary/methods , Malaria Vaccines/administration & dosage , Male , Phosphates/administration & dosage , Placebos/administration & dosage , Plasmodium falciparum/growth & development , Plasmodium falciparum/immunology , Protozoan Proteins/administration & dosage , United States , Vaccination/methods , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/immunology , Young AdultABSTRACT
BACKGROUND: Traveler's diarrhea is the most common medical complaint of international visitors to developing regions. Previous findings suggested that noroviruses (NoVs) are an underappreciated cause of traveler's diarrhea. METHODS. In the present study, we sought to define the presence of NoVs in 320 acute diarrheic stool samples collected from 299 US students who traveled to Guadalajara, Cuernavaca, or Puerto Vallarta, Mexico, during the period from 2007 through 2008. Conventional and quantitative real-time polymerase chain reaction assays were used to detect and determine NoV loads in stool samples. NoV strains were characterized by purification of viral RNA followed by sequencing of the viral capsid protein 1 gene. Sequences were compared using multiple sequence alignment, and phylogenetic trees were generated to evaluate the evolutionary relatedness of the viral strains associated with cases of traveler's diarrhea. RESULTS: NoV RNA was detected in 30 (9.4%) of 320 samples. Twelve strains belonged to genogroup I, and 18 strains belonged to genogroup II. NoV prevalence was higher in the winter season than in the summer season (23% vs 7%, respectively; P = .001). The cDNA viral loads of genogroup I viruses were found to be 500-fold higher than those of genogroup II strains. Phylogenetic analysis revealed a diverse population of NoV strains over different locations and years. CONCLUSIONS: NoV strains are important causes of traveler's diarrhea in Mexico, especially during the wintertime, and US students in Mexico may represent a suitable group for future NoV vaccine efficacy trials.
Subject(s)
Caliciviridae Infections/epidemiology , Caliciviridae Infections/virology , Gastroenteritis/epidemiology , Gastroenteritis/virology , Norovirus/isolation & purification , Travel , Adult , Caliciviridae Infections/pathology , Capsid Proteins/genetics , Cluster Analysis , Diarrhea/epidemiology , Diarrhea/pathology , Diarrhea/virology , Feces/virology , Female , Gastroenteritis/pathology , Genotype , Humans , Male , Mexico , Middle Aged , Molecular Epidemiology , Norovirus/classification , Norovirus/genetics , Phylogeny , Polymerase Chain Reaction , RNA, Viral/genetics , Sequence Analysis, DNA , Sequence Homology , United States , Viral Load , Young AdultABSTRACT
We evaluated the safety, reactogenicity and immunogenicity of escalating doses of a new Francisella tularensis Live Vaccine Strain (LVS) lot by scarification (SCAR) or subcutaneously (SQ) in humans. Subjects (N=10/group) received one dose of LVS via SCAR at 10(5),10(7) or 10(9)cfu/ml or SQ at 10(2), 10(3),10(4) or 10(5)cfu/ml; 14 subjects received placebo. All doses/routes were well tolerated. When compared to placebo, vaccination with 10(7) SCAR and 10(9) SCAR resulted in significantly higher serologic response frequencies, as measured by ELISA for IgG, IgM, IgA and microagglutination; whereas vaccination with 10(5) SCAR, 10(7) SCAR 10(9) SCAR and 10(5) SQ elicited a significantly higher interferon-gamma response frequency.
Subject(s)
Bacterial Vaccines/adverse effects , Bacterial Vaccines/immunology , Francisella tularensis/immunology , Adolescent , Adult , Antibodies, Bacterial/blood , Bacterial Vaccines/administration & dosage , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Injections, Subcutaneous , Interferon-gamma/blood , Male , Placebos/administration & dosage , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/immunology , Young AdultABSTRACT
Real-time RT-PCR, combining amplification and detection of virus-specific amplicons, is a promising tool for norovirus detection in environmental or food samples such as shellfish. We developed a real-time RT-PCR assay based on one-step detection using single primer sets and probes for norovirus genogroups I and II. Seventy and seven RT-PCR units of genogroup I and II reference norovirus strains, respectively, were detected in artificially contaminated oysters. Validation of the new method on 150 archived naturally contaminated shellfish confirmed the utility of the genogroup II primer set to detect a large range of different strains circulating in France since 1995, but genogroup I strains were detected infrequently.
Subject(s)
Norovirus/isolation & purification , Ostreidae/virology , Shellfish/virology , Animals , DNA Primers , Norovirus/classification , Norovirus/genetics , RNA, Viral/analysis , RNA, Viral/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and SpecificitySubject(s)
ABO Blood-Group System , Caliciviridae Infections/epidemiology , Cross Infection/epidemiology , Disease Outbreaks , Gastroenteritis/epidemiology , Norovirus/isolation & purification , Caliciviridae Infections/blood , Caliciviridae Infections/etiology , Caliciviridae Infections/prevention & control , Cross Infection/blood , Cross Infection/etiology , Cross Infection/prevention & control , Gastroenteritis/blood , Gastroenteritis/etiology , Gastroenteritis/prevention & control , Germany/epidemiology , Humans , Medical Staff , PatientsABSTRACT
Co-circulating variants of influenza A/H3N2 viruses in children were studied in Houston, Texas between October 1997 and March 1998 to assess the effects of a new variant strain on the severity of clinical illness. Influenza A virus was isolated from the nasal wash or nasal aspirate specimens collected from children at two tertiary care hospitals, and 271 isolates were available for variant-specific subtyping using RT-PCR and restriction fragment length polymorphism (RFLP) analysis. We classified 124 (46%) influenza viruses as A/H3N2/Wuhan/359/95-like and 137 (50%) as A/H3N2/Sydney/05/97-like. Ten (4%) virus isolates could not be classified. Ill contacts in the household were reported more frequently in patients infected with A/Sydney-like viruses than in those infected with A/Wuhan-like viruses (85% vs. 71%, respectively, P=0.02). There were no differences in other demographic variables among children infected with these strains. This study found no increase in illness severity in children infected with a newly emerging strain.
Subject(s)
Communicable Diseases, Emerging/epidemiology , Influenza A Virus, H3N2 Subtype , Influenza A virus/classification , Influenza A virus/genetics , Influenza, Human/epidemiology , Child , Child, Preschool , Communicable Diseases, Emerging/prevention & control , Communicable Diseases, Emerging/virology , Comorbidity , Female , Humans , Infant , Infant, Newborn , Influenza, Human/prevention & control , Influenza, Human/virology , Male , Molecular Epidemiology , Multivariate Analysis , Odds Ratio , Polymorphism, Restriction Fragment Length , Prevalence , Proportional Hazards Models , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , Texas/epidemiologyABSTRACT
The frequency of colonization and intracellular localization of nontypeable Haemophilus influenzae (NTHi) in the lower respiratory tract was determined in healthy adults and in clinically stable and acutely ill chronic bronchitis (CB) patients. NTHi was recovered from bronchial wash or bronchial brush specimens in 6 of 23 (26%) stable CB patients and in 1 of 15 (7%) CB patients with a respiratory exacerbation. No NTHi (0 of 26) was recovered from lower tract specimens of healthy adults undergoing anesthesia for elective surgery. Molecular typing of NTHi strains revealed that five of nine patients with stable CB had different strains in upper respiratory tract and bronchial wash/brush specimens collected simultaneously. Four stable patients with CB had different strains recovered on repeat bronchoscopy. These results demonstrate the frequent colonization of the lower airways of stable CB patients with multiple strains of NTHi. Bronchial biopsies also were examined for intracellular NTHi by in situ hybridization and immunofluorescence microscopy. Intracellular NTHi were found in 0 of 7 healthy adults, 8 of 24 patients with clinically stable CB, and 13 of 15 acutely ill CB patients. This observation suggests a role for intracellular infection by NTHi in the pathogenesis of exacerbations of CB.
Subject(s)
Bronchitis, Chronic/complications , Carrier State/microbiology , Haemophilus Infections/complications , Haemophilus Infections/microbiology , Haemophilus influenzae/classification , Acute Disease , Adult , Aged , Biopsy , Bronchoalveolar Lavage , Bronchoscopy , Case-Control Studies , DNA, Bacterial/analysis , DNA, Bacterial/genetics , Female , Fluorescent Antibody Technique , Haemophilus influenzae/genetics , Humans , In Situ Hybridization , Male , Middle Aged , Phenotype , Polymerase Chain Reaction , Ribotyping , Sputum/microbiologyABSTRACT
The immunogenicity and safety of a chromatographically purified rabies vaccine (CPRV) was evaluated using US veterinary medical students. In the first study, 242 healthy adults were enrolled in a randomized, modified double-blind, multicenter trial and received five doses of either CPRV or human diploid cell vaccine (HDCV) by intramuscular injection on days 0, 3, 7, 14, and 28 concurrently with human rabies immunoglobulin in a simulated post-exposure prophylaxis regimen. Post-immunization titers in the CPRV and HDCV groups reached 0.5 IU/ml (the WHO-recommended minimally acceptable titer) or greater in all subjects in both vaccine groups by day 14 and remained above that level through day 90. In the second study, 438 healthy adults were enrolled in a randomized, double-blind, multicenter trial and assigned to receive five doses from one of three lots of CPRV by intramuscular injection on days 0, 3, 7, 14, and 28 in a simulated post-exposure prophylaxis regimen to evaluate lot consistency. Post-immunization titers rapidly increased to over 0.5 IU/ml by day 14 for all subjects and remained above that level through day 42 when the study was terminated. The three lots were considered equivalent. The percentage of subjects with at least one local reaction during the five-dose regimen was slightly lower in the CPRV group than in the HDCV group (P=0.06). The most frequently reported local reaction for all doses of vaccine was pain at the injection site. Headache, myalgia, and malaise were the most frequently reported systemic events. The percentage of subjects with at least one systemic event was significantly lower for CPRV (P=0.0084). No vaccine-related serious adverse reaction was reported in these studies. The results of these studies indicate that CPRV administered intramuscularly to healthy adults is immunogenic and is associated with fewer local and systemic reactions than HDCV.
Subject(s)
Antibodies, Viral/biosynthesis , Rabies Vaccines/immunology , Rabies virus/immunology , Adult , Animals , Antibodies, Viral/administration & dosage , Chlorocebus aethiops , Chromatography , Double-Blind Method , Erythema/etiology , Female , Headache/etiology , Humans , Immunization Schedule , Injections, Intramuscular , Lymphadenitis/etiology , Male , Pain/etiology , Propiolactone/pharmacology , Prospective Studies , Pruritus/etiology , Rabies Vaccines/administration & dosage , Rabies Vaccines/adverse effects , Rabies Vaccines/isolation & purification , Rabies Vaccines/standards , Rabies virus/drug effects , Rabies virus/growth & development , Safety , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology , Vaccines, Inactivated/isolation & purification , Vaccines, Inactivated/standards , Vero Cells/virology , Virus CultivationABSTRACT
Outbreaks of food- and waterborne gastroenteritis are being increasingly reported throughout the world. The analysis of environmental samples by newer diagnostic techniques such as reverse transcription-PCR (RT-PCR) amplification of nucleic acid has begun to identify human enteric viruses (predominantly "Norwalk-like" viruses [NLVs]) as the cause of many of these outbreaks. To streamline NLV detection from environmental samples such as shellfish, we have developed an RT-PCR-oligoprobe amplification and detection method using several new procedures that enable confirmed RT-PCR amplification and product detection in 1 day. The new steps include replacing reverse transcriptase and Taq polymerase with rTth polymerase, a heat-stable enzyme that functions as both a reverse transcriptase and DNA polymerase, in a single-tube, single-buffer, elevated temperature reaction. An internal standard Norwalk virus (NV) RNA control is added to each RT-PCR to identify sample inhibition, and thermolabile uracil N-glycosylase is incorporated into the reaction to prevent PCR product carryover contamination. Finally, RT-PCR-generated amplicons are detected in microtiter wells using virus-specific biotinylated oligoprobes in an enzyme-linked immunosorbent assay-based format. The DNA enzyme immunoassay is based on the capture of PCR product by biotinylated probes fixed onto individual streptavidin-coated wells. Using this method, low levels of NV were detected in stool and both NLV and hepatitis A virus were detected in bivalve mollusks following bioaccumulation. The method also successfully detected NLV in oysters implicated in an outbreak of NLV gastroenteritis. This method dramatically decreases the time needed for analysis and is amenable to automation.
Subject(s)
Bivalvia/virology , Norwalk virus/isolation & purification , Ostreidae/virology , Reverse Transcriptase Polymerase Chain Reaction , Shellfish/virology , Animals , Caliciviridae Infections/epidemiology , Caliciviridae Infections/virology , DNA, Viral/analysis , Disease Outbreaks , Feces/virology , Gastroenteritis/epidemiology , Gastroenteritis/virology , Hepatitis A/virology , Hepatovirus/genetics , Hepatovirus/isolation & purification , Humans , Immunoenzyme Techniques , Norwalk virus/genetics , Sensitivity and SpecificityABSTRACT
Gastroenteritis is one of the most common illnesses of humans, and many different viruses have been causally associated with this disease. Of those enteric viruses that have been established as etiologic agents of gastroenteritis, only the human caliciviruses cannot be cultivated in vitro. The cloning of Norwalk virus and subsequently of other human caliciviruses has led to the development of several new diagnostic assays. Antigen detection enzyme immunoassays (EIAs) using polyclonal hyperimmune animal sera and antibody detection EIAs using recombinant virus-like particles have supplanted the use of human-derived reagents, but the use of these assays has been restricted to research laboratories. Reverse transcription-PCR assays for the detection of human caliciviruses are more widely available, and these assays have been used to identify virus in clinical specimens as well as in food, water, and other environmental samples. The application of these newer assays has significantly increased the recognition of the importance of human caliciviruses as causes of sporadic and outbreak-associated gastroenteritis.
Subject(s)
Caliciviridae Infections/diagnosis , Caliciviridae/isolation & purification , Gastroenteritis/diagnosis , Immunologic Tests/methods , Caliciviridae/classification , Caliciviridae/ultrastructure , Gastroenteritis/etiology , Gastroenteritis/virology , Genotype , Humans , Microscopy, Electron , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction/standardsABSTRACT
Norwalk virus (NV) is the prototype human virus of the family Caliciviridae. A rapid immunomagnetic capture/reverse transcription-(IMC/RT-)PCR assay was developed for the detection of NV. Immunomagnetic capture (IMC) utilizes paramagnetic beads coupled to a virus-specific antibody and allows separation of virus from contaminating materials and virus concentration in a single step. The detection limit of the developed assay was approximately 250-750 genomic equivalents/ml of 10% stool suspension. The detection limit of the assay was not altered by the presence of excess hepatitis A virus (HAV), although non-specific binding of HAV to the paramagnetic beads was observed. A panel of 100 stools from experimental human infections was screened for NV using a previously described heat release method, an antigen ELISA, or IMC/RT-PCR. NV was detected in 65/100 of these samples by IMC/RT-PCR compared to only 38/99 by heat release and 31/95 by antigen detection ELISA. All samples that were negative by IMC were also negative by both heat release and antigen ELISA. The number of samples in which RT-PCR was inhibited was greatly reduced by the use of IMC/RT-PCR compared to the heat release method (1/100 and 16/95 samples inhibited, respectively). The ability of IMC to concentrate virus (> or =2000-fold greater than heat release) and effectively remove inhibitory substances gives this assay distinct advantages over both the heat release and antigen ELISAs.
Subject(s)
Immunomagnetic Separation , Norwalk virus/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction , Caliciviridae Infections/virology , Feces/virology , Gastroenteritis/virology , Humans , Sensitivity and SpecificityABSTRACT
The viruses associated most frequently with the "common cold" are rhinoviruses and coronaviruses. The first prospective cohort study to determine the prevalence of rhinovirus and coronavirus infections in patients of all ages hospitalized for acute respiratory illnesses is described. Hospital admissions for acute respiratory illnesses were identified, and cell culture for rhinovirus and serologic assays on paired sera for coronaviruses 229E and OC43 were performed. A total of 61 infections with rhinoviruses and coronaviruses were identified from 1198 respiratory illnesses (5.1%); in addition, 9 additional infections associated with >/=1 other respiratory viruses were identified. Of those infected with only rhinovirus or coronavirus, underlying cardiopulmonary diseases were present in 35% of the patients aged <5 years, in 93% aged between 5 and 35 years, and in 73% aged >35 years. The predominant clinical syndromes varied by age: pneumonia and bronchiolitis in children aged <5 years; exacerbations of asthma in older children and young adults; and pneumonia and exacerbations of chronic obstructive pulmonary disease and congestive heart failure in older adults. Therefore, rhinovirus and coronavirus infections in hospitalized patients were associated with lower respiratory tract illnesses in all age groups.
Subject(s)
Common Cold/physiopathology , Coronavirus Infections/epidemiology , Rhinovirus , Adolescent , Adult , Child , Child, Preschool , Common Cold/epidemiology , Common Cold/virology , Coronavirus Infections/virology , Female , Hospitals , Humans , Infant , Male , Prevalence , Prospective StudiesABSTRACT
A longitudinal cohort study of older adults with chronic obstructive pulmonary disease (COPD) who were stratified by FEV(1) at enrollment was done to define the etiology, frequency, severity, and medical-care impact of respiratory tract viral infections (RTVIs). Controls consisted of a group of subjects of comparable age with the patients. RTVIs were documented in 44% of observed acute respiratory illnesses in control subjects and in 27% of COPD subjects, who were followed for mean periods of 35 and 26 mo, respectively. In this heavily influenza-vaccinated cohort ( approximately 90% vaccinated each year), picornaviruses, parainfluenza viruses, and coronaviruses were most commonly identified. Mean time to return to clinical baseline was approximately 2 wk in each group. Control and COPD subjects with mild airways obstruction (baseline FEV(1) >/= 50% predicted) had few emergency-center visits or hospitalizations. Approximately half of COPD subjects with moderate/severe COPD (baseline FEV(1) < 50% predicted) had at least one emergency-center visit and/or hospitalization for acute respiratory illness. RTVIs were documented in 23% of hospitalizations and in 45% of patients admitted between December and March. RTVIs have a major impact on utilization of health care resources for COPD patients with moderate/severe airways obstruction.
Subject(s)
Lung Diseases, Obstructive/complications , Respiratory Tract Diseases/complications , Respiratory Tract Diseases/virology , Virus Diseases/complications , Aged , Female , Hospitalization/statistics & numerical data , Humans , Influenza Vaccines , Longitudinal Studies , Male , Middle Aged , Respiratory Tract Diseases/epidemiology , Respiratory Tract Diseases/prevention & control , Time Factors , Virus Diseases/epidemiologyABSTRACT
In March 1998, an outbreak of acute gastroenteritis occurred among students at a Texas university. Overall, 125 ill students sought medical care. Case-control studies revealed that illness was significantly associated with eating foods from the university's main cafeteria deli bar on 9 and 10 March. Stool specimens from 9 (50%) of 18 ill students and samples of deli ham showed evidence of Norwalk-like viruses (NLVs) by reverse-transcriptase (RT) polymerase chain reaction (PCR) assay. A food handler who prepared sandwiches for lunch on 9 March reported that her infant had been sick with watery diarrhea since just before the outbreak. A stool sample from the infant was positive for NLV by RT-PCR, and the sequence of the amplified product was identical to that of amplified product from deli ham and students' stool specimens. This is the first time RT-PCR and sequence analysis have successfully confirmed viral contamination of a food item likely to have been contaminated by a food handler.
Subject(s)
Caliciviridae Infections/epidemiology , Caliciviridae Infections/virology , Disease Outbreaks , Foodborne Diseases/epidemiology , Foodborne Diseases/virology , Gastroenteritis/epidemiology , Gastroenteritis/virology , Norwalk virus , Adolescent , Adult , Caliciviridae Infections/transmission , Case-Control Studies , Diarrhea/virology , Feces/microbiology , Feces/virology , Female , Food Handling , Humans , Infant , Male , Polymerase Chain Reaction , Texas , UniversitiesABSTRACT
The performance of a new, rapid, easy-to-perform assay based on neuraminidase enzyme activity for detection of influenza virus types A and B was compared to detection by culture, indirect immunofluorescence, and enzyme immunoassay in 479 nasal wash specimens from children with respiratory infections. Compared to isolation of influenza virus by culture, the neuraminidase assay had a sensitivity of 70.1%, specificity of 92.4%, positive predictive value of 76.3%, and negative predictive value of 89.9%. There was a higher sensitivity for the detection of influenza A virus (76.4%) than for influenza B virus (40.9%). Indirect immunofluorescence showed a sensitivity of 59.8% and specificity of 97% compared to culture isolation for detection of influenza A and B viruses. Enzyme immunoassay showed a sensitivity of 89.7% and specificity of 98.1% for the detection of influenza A alone. The quality of the nasal wash specimen had a significant effect on the detection of influenza virus by all of the assays. A strong response of the neuraminidase assay was more likely to represent a culture-confirmed influenza infection. This new rapid neuraminidase assay was useful for the detection of influenza A and B viruses in nasal wash specimens.
Subject(s)
Influenza A virus/isolation & purification , Influenza B virus/isolation & purification , Influenza, Human/diagnosis , Nasal Mucosa/virology , Neuraminidase/analysis , Fluorescent Antibody Technique, Indirect , Humans , Immunoassay , Influenza A virus/enzymology , Influenza B virus/enzymology , Predictive Value of Tests , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and SpecificityABSTRACT
CONTEXT: While hospitalization rates have declined overall, hospitalizations for acute lower respiratory tract infections have increased steadily since 1980. Development of new approaches for prevention of acute respiratory tract conditions requires studies of the etiologies of infections and quantification of the risk of hospitalization for vulnerable patients. OBJECTIVE: To determine the frequency of specific virus infections associated with acute respiratory tract conditions leading to hospitalization of chronically ill patients. DESIGN: Analysis of viral etiology of patients hospitalized with acute respiratory tract conditions between July 1991 and June 1995. SETTING: Four large clinics and related hospitals serving diverse populations representative of Harris County, Texas. PATIENTS: A total of 1029 patients who were hospitalized for pneumonia, tracheobronchitis, bronchiolitis, croup, exacerbations of asthma or chronic obstructive pulmonary disease, and/or congestive heart failure. MAIN OUTCOME MEASURE: Virus infection, defined by culture, antigen detection, and significant rise in serum antibodies, by underlying condition; hospitalization rates by low- vs middle-income status. RESULTS: Ninety-three percent of patients older than 5 years had a chronic underlying condition; a chronic pulmonary condition was most common. Patients with chronic pulmonary disease from low-income populations were hospitalized at a rate of 398.6 per 10000, almost 8 times higher than the rate for patients from middle-income groups (52.2 per 10000; P<.001). Of the 403 patients (44.4% of adults and 32.3% of children) who submitted convalescent serum specimens for antibody testing, respiratory tract virus infections were detected in 181 (44.9%). Influenza, parainfluenza, and respiratory syncytial virus (RSV) infections accounted for 75% of all virus infections. CONCLUSIONS: Our study suggests that respiratory virus infections commonly trigger serious acute respiratory conditions that result in hospitalization of patients with chronic underlying conditions, highlighting the need for development of effective vaccines for these viruses, especially for parainfluenza and RSV.