Showing papers in "The Journal of Infectious Diseases in 2002"
TL;DR: Information on age- and sex-specific prevalence of herpes simplex virus (HSV) types 2 and 1 infections is essential to optimize genital herpes control strategies, which increase in importance because accumulating data indicate that HSV-2 infection may increase acquisition and transmission of human immunodeficiency virus.
Abstract: Information on age- and sex-specific prevalence of herpes simplex virus (HSV) types 2 and 1 infections is essential to optimize genital herpes control strategies, which increase in importance because accumulating data indicate that HSV-2 infection may increase acquisition and transmission of human immunodeficiency virus. This review summarizes data from peer-reviewed publications of type-specific HSV seroepidemiologic surveys. HSV-2 prevalence is, in general, highest in Africa and the Americas, lower in western and southern Europe than in northern Europe and North America, and lowest in Asia. HSV-2 and -1 prevalence, overall and by age, varies markedly by country, region within country, and population subgroup. Age-specific HSV-2 prevalence is usually higher in women than men and in populations with higher risk sexual behavior. HSV-2 prevalence has increased in the United States but national data from other countries are unavailable. HSV-1 infection is acquired during childhood and adolescence and is markedly more widespread than HSV-2 infection. Further studies are needed in many geographic areas.
813 citations
TL;DR: These results expand published findings demonstrating that immunization by exposure to thousands of mosquitoes carrying radiation-attenuated Pf sporozoites is safe and well tolerated and elicits strain-transcendent protective immunity that persists for at least 42 weeks.
Abstract: During 1989-1999, 11 volunteers were immunized by the bites of 1001-2927 irradiated mosquitoes harboring infectious sporozoites of Plasmodium falciparum (Pf) strain NF54 or clone 3D7/NF54. Ten volunteers were first challenged by the bites of Pf-infected mosquitoes 2-9 weeks after the last immunization, and all were protected. A volunteer challenged 10 weeks after the last immunization was not protected. Five previously protected volunteers were rechallenged 23-42 weeks after a secondary immunization, and 4 were protected. Two volunteers were protected when rechallenged with a heterologous Pf strain (7G8). In total, there was protection in 24 of 26 challenges. These results expand published findings demonstrating that immunization by exposure to thousands of mosquitoes carrying radiation-attenuated Pf sporozoites is safe and well tolerated and elicits strain-transcendent protective immunity that persists for at least 42 weeks.
722 citations
TL;DR: Stx2c-positive STEC isolates can cause HUS, but the presence of stx2d or stX2e may predict a milder disease with a minimal risk of HUS.
Abstract: Shiga toxin (Stx)-producing Escherichia coli (STEC) from patients with hemolytic-uremic syndrome (HUS), patients with diarrhea without HUS, or asymptomatic subjects were genotyped to assess associations between stx2 variants and clinical manifestations of infection. Neither stx2d nor stx2e was found in 268 STEC isolates from patients with HUS. Of 262 STEC isolates from patients with diarrhea, stx(2d) was found in 41 (15.6%; P<.000001), and stx2e was found in 12 (4.6%; P=.0004). The stx2c genotype frequency was similar among isolates from patients with HUS (3.7%) and diarrhea (5.0%). The frequencies of stx2c, stx2d, and stx2e among 96 STEC isolates from asymptomatic subjects were comparable to those among isolates from patients with diarrhea. None of the 626 STEC isolates contained stx2f. All stx2d-positive or stx2e-positive STEC isolates were eae negative and originated from subjects older than those with STEC isolates with stx2c. stx2c-positive STEC isolates can cause HUS, but the presence of stx2d or stx2e may predict a milder disease with a minimal risk of HUS.
720 citations
TL;DR: Control strategies for HSV-2 need to be incorporated into control of sexually transmitted infections as a strategy for HIV prevention.
Abstract: To determine the contribution of herpes simplex type 2 (HSV-2) infection to the risk of human immunodeficiency virus (HIV) acquisition, a systematic review of literature and data synthesis were done. Thirty-one studies addressed the risk of HIV infection in HSV-2-seropositive persons. For 9 cohort and nested case-control studies that documented HSV-2 infection before HIV acquisition, the risk estimate was 2.1 (95% confidence interval, 1.4-3.2). Thus, the attributable risk percentage of HIV to HSV-2 was 52%, and the population attributable risk percentage was 19% in populations with 22% HSV-2 prevalence but increased to 47% in populations with 80% HSV-2 prevalence. For 22 case-control and cross-sectional studies, the risk estimate was 3.9 (95% confidence interval, 3.1-5.1), but the temporal sequence of the 2 infections cannot be documented. Control strategies for HSV-2 need to be incorporated into control of sexually transmitted infections as a strategy for HIV prevention.
695 citations
TL;DR: In this paper, the secreted dengue virus nonstructural protein NS1 (sNS1) was measured daily in 32 children with Dengue-2 virus infections participating in a prospective, hospital-based study.
Abstract: Infection with any 1 of 4 dengue viruses produces a spectrum of clinical illness ranging from a mild undifferentiated febrile illness to dengue fever (DF) to dengue hemorrhagic fever (DHF), a potentially life-threatening disease. The morbidity and mortality of DHF can be reduced by early hospitalization and careful supportive care. To determine its usefulness as a predictor of DHF, plasma levels of the secreted dengue virus nonstructural protein NS1 (sNS1) were measured daily in 32 children with dengue-2 virus infections participating in a prospective, hospital-based study. Free sNS1 levels in plasma correlated with viremia levels and were higher in patients with DHF than in those with DF. An elevated free sNS1 level (> or =600 ng/mL) within 72 h of illness onset identified patients at risk for developing DHF.
646 citations
TL;DR: This international collaborative survey identified culture-confirmed Legionellosis in 508 patients with sporadic community-acquired legionellosis and identified the Legionella species most commonly isolated in Australia and New Zealand.
Abstract: This international collaborative survey identified culture-confirmed legionellosis in 508 patients with sporadic community-acquired legionellosis. Legionella pneumophila constituted 91.5% of the isolates. Serogroup 1 was the predominant serogroup (84.2%), and serogroups 2-13 (7.4%) accounted for the remaining serogroups. The Legionella species most commonly isolated were L. longbeachae (3.9%) and L. bozemanii (2.4%), followed by L. micdadei, L. dumoffii, L. feeleii, L. wadsworthii, and L. anisa (2.2% combined). L. longbeachae constituted 30.4% of the community-acquired Legionella isolates in Australia and New Zealand.
637 citations
TL;DR: Fecal specimens from 284 outbreaks of nonbacterial gastroenteritis were submitted to the Centers for Disease Control and Prevention for testing for "Norwalk-like viruses" (NLVs), and 217 of these were positive for NLVs.
Abstract: Between July 1997 and June 2000, fecal specimens from 284 outbreaks of nonbacterial gastroenteritis were submitted to the Centers for Disease Control and Prevention for testing for "Norwalk-like viruses" (NLVs). Specimens were examined by reverse-transcription polymerase chain reaction and direct electron microscopy for the presence of NLVs. Adequate descriptive data were available from 233 of the outbreaks, and, of these, 217 (93%) were positive for NLVs. Restaurants and events with catered food were the most common settings, and contaminated food was the most common mode of transmission. Genogroup II (GII) strains were the predominant type (73%), with genogroup I strains causing 26% of all NLV-positive outbreaks. Certain GII clusters (GII/1,4,j) were more commonly associated with outbreaks in nursing home settings than with outbreaks in other settings. Strain diversity was great: one potential new sequence cluster was implicated in multiple outbreaks, and strains belonging to a tentative new genogroup were identified.
599 citations
TL;DR: Findings indicate that hTLR4 mutations are associated with an increased incidence of gram-negative infections in critically ill patients in a surgical setting.
Abstract: Human toll-like receptor 4 (hTLR4) and CD14 are known to be components of the lipopolysaccharide receptor complex. Our study investigated the association between TLR4 mutations (Asp299Gly and Thr399Ile) and CD14 polymorphism(s) with outcome in an intensive care unit (ICU) population at risk for sepsis. By use of a polymerase chain reaction-based restriction fragment-length polymorphism analysis technique, the hTLR4 gene was altered in 14 (18%) of 77 ICU patients (all positive for systemic inflammatory response syndrome) and in 5 (13%) of 39 volunteers. There was a significantly higher incidence of gram-negative infection among patients with the mutations (11 [79%] of 14), compared with that in the wild-type population (11 [17%] of 63; P=.004). No association between CD14 polymorphism(s) and the incidence of infection or outcome was observed. These findings indicate that hTLR4 mutations are associated with an increased incidence of gram-negative infections in critically ill patients in a surgical setting.
575 citations
TL;DR: The virological features and clinical findings associated with the new human metapneumovirus (HMPV) were examined retrospectively in Canadian patients hospitalized for various respiratory conditions since 1993 and suggest that HMPV can be associated with severe lower-respiratory-tract infections in very young children, the elderly, and immunocompromised patients.
Abstract: The virological features and clinical findings associated with the new human metapneumovirus (HMPV) were examined retrospectively in Canadian patients hospitalized for various respiratory conditions since 1993 Thirty-eight previously unidentified respiratory viruses isolated from rhesus monkey kindey (LLC-MK2) cells were found to be positive for HMPV by reverse-transcription polymerase chain reaction, and those strains clustered in 2 phylogenetic groups Children aged 65 years represented 351% and 459% of the HMPV-infected cases, respectively In hospitalized children, the most frequent diagnoses were pneumonitis (667%) and bronchiolitis (583%), whereas bronchitis and/or bronchospasm (60%) and pneumonitis (40%) were most commonly seen in elderly subjects Of the 15 patients with pneumonitis, 4 (267%) had immunosuppressive conditions and 6 (40%) were infants aged <15 months These findings suggest that HMPV can be associated with severe lower-respiratory-tract infections in very young children, the elderly, and immunocompromised patients
555 citations
TL;DR: Infections caused by parasites with 3 DHFR mutations and 2 DHPS mutations (the "quintuple mutant") were associated with sulfadoxine-pyrimethamine treatment failure but not with chlorproguanil-dapsone treatment failure.
Abstract: Molecular assays for monitoring sulfadoxine-pyrimethamine-resistant Plasmodium falciparum have not been implemented because of the genetic and statistical complexity of the parasite mutations that confer resistance and their relation to treatment outcomes. This study analyzed pretreatment dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genotypes and treatment outcomes in a double-blind, placebo-controlled trial of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment for uncomplicated P. falciparum malaria. Multiple logistic regression was used to identify mutations that were predictive of treatment failure and to identify interactions and confounding factors. Infections caused by parasites with 3 DHFR mutations and 2 DHPS mutations (the "quintuple mutant") were associated with sulfadoxine-pyrimethamine treatment failure but not with chlorproguanil-dapsone treatment failure. The presence of a single DHFR mutation (Arg-59) with a single DHPS mutation (Glu-540) accurately predicted the presence of the quintuple mutant. If this model is validated in other populations, it will finally be possible to use molecular markers for surveillance of antifolate-resistant P. falciparum malaria in Africa.
502 citations
TL;DR: Functional activity of Combination B against P. falciparum is demonstrated in individuals with previous malaria exposure and the specific effects on parasites with particular msp2 genotypes suggest that the MSP2 component, at least in part, accounted for the activity.
Abstract: The malaria vaccine Combination B comprises recombinant Plasmodium falciparum ring-infected erythrocyte surface antigen and 2 merozoite surface proteins (MSP1 and MSP2) formulated in oil-based adjuvant. A phase 1-2b double-blind, randomized, placebo-controlled trial in 120 children (5-9 years old) in Papua New Guinea demonstrated a 62% (95% confidence limits: 13%, 84%) reduction in parasite density in children not pretreated with sulfadoxine-pyrimethamine. Vaccinees had a lower prevalence of parasites carrying the MSP2-3D7 allelic form (corresponding to that in the vaccine) and a higher incidence of morbid episodes associated with FC27-type parasites. These results demonstrate functional activity of Combination B against P. falciparum in individuals with previous malaria exposure. The specific effects on parasites with particular msp2 genotypes suggest that the MSP2 component, at least in part, accounted for the activity. The vaccine-induced selection pressure exerted on the parasites and its consequences for morbidity strongly argue for developing vaccines comprising conserved antigens and/or multiple components covering all important allelic types.
TL;DR: Quantitative differences in virus burden and host immune responses, and the timing of type 1 cytokine responses, have differing influences on the severity of disease manifestations during secondary dengue-3 virus infections.
Abstract: Dengue hemorrhagic fever (DHF), the most severe form of illness following infection with a dengue virus, is characterized by plasma leakage, thrombocytopenia, and hepatic inflammation. The interrelationships among virus burden, immune activation, and development of DHF were examined in 54 children with secondary dengue-3 virus infections participating in a prospective, hospital-based study. DHF was associated with higher mean plasma viremia early in illness and earlier peak plasma interferon-γ levels. Maximum plasma viremia levels correlated with the degree of plasma leakage and thrombocytopenia. Maximum plasma levels of interleukin (IL)-10 and soluble tumor necrosis factor receptor-II correlated with the degree of thrombocytopenia, independently of viremia levels. Hepatic transaminase elevation correlated with plasma soluble IL-2 receptor levels and not with viremia levels. Quantitative differences in virus burden and host immune responses, and the timing of type 1 cytokine responses, have differing influences on the severity of disease manifestations during secondary dengue-3 virus infections.
TL;DR: Ind isolation of influenzavirus was associated with an estimated 95 health care visits for children with symptoms of influenza, 46 episodes of acute otitis media, and 8 episodes of lower respiratory tract disease per 1000 children yearly.
Abstract: Many respiratory viruses cause morbidity in young children, but a licensed vaccine and effective oral therapy are available only for influenzavirus. To determine the incidence of laboratory-confirmed influenza illness, we prospectively followed up 1665 healthy children aged <5 years who were enrolled in the Vanderbilt Vaccine Clinic at some point from 1974 through 1999. Viral cultures were obtained when the children presented with clinical illness. The isolation of influenzavirus was associated with an estimated 95 health care visits for children with symptoms of influenza, 46 episodes of acute otitis media, and 8 episodes of lower respiratory tract disease per 1000 children yearly. Rates of acute otitis media and lower respiratory tract disease were highest among children aged <2 years. Hospitalizations associated with culture-positive influenza occurred at an annual rate of 3-4 per 1000 children aged <2 years. Influenza is associated with substantial morbidity in otherwise healthy children aged <5 years.
TL;DR: To study the influence of Toxoplasma gondii genotypes on the severity of human congenital toxoplasmosis (asymptomatic, benign, or severe infection or newborn or fetal death), 8 microsatellite markers were used and type II isolates were largely predominant.
Abstract: To study the influence of Toxoplasma gondii genotypes on the severity of human congenital toxoplasmosis (asymptomatic, benign, or severe infection or newborn or fetal death), 8 microsatellite markers were used to analyze 86 T. gondii isolates collected from patients with congenital toxoplasmosis. Seventy-four different genotypes were detected, some identical genotypes originating probably from the same source of contamination. The 3 less polymorphic microsatellite markers associated with 6 isoenzymatic markers allowed a classification of isolates into the 3 classical types and detected atypical genotypes. Whatever the clinical findings, type II isolates were largely predominant (84.88% in the whole collection and 96.49% in 57 consecutive cases). Type I and atypical isolates were not found in asymptomatic or benign congenital toxoplasmosis. However, in 4 cases in which children were not infected despite isolation of T. gondii from placenta, only type I isolates were found.
TL;DR: A summary of the laboratory tests currently available at TSL-PAMFRI for the diagnosis of infection and disease caused by the parasite is presented here.
Abstract: For the past 40 years, the Toxoplasma Serology Laboratory at the Palo Alto Medical Foundation Research Institute (TSL-PAMFRI) has been dedicated to the laboratory diagnosis of Toxoplasma gondii infection and toxoplasmosis. TSL-PAMFRI is the "brain child" of Jack S. Remington. Jack's ceaseless devotion to objectivity and uncompromising excellence has made TSL-PAMFRI the Toxoplasma reference laboratory for the Centers for Disease Control and Prevention, the US Food and Drug Administration, and health care providers and clinical laboratories in the United States and other countries. Jack's leadership and vision created, defined, and significantly contributed to the development of laboratory methods for the diagnosis of the infection and diseases caused by T. gondii. A summary of the laboratory tests currently available at TSL-PAMFRI for the diagnosis of infection and disease caused by the parasite is presented here.
TL;DR: It is concluded that TLR4-defective C3H/HeJ mice are more susceptible to C. albicans infection, and this is associated with impaired chemokine expression and neutrophil recruitment.
Abstract: Toll-like receptors (TLRs) represent the main class of pattern-recognition receptors involved in sensing pathogenic microorganisms. The aim of the present study was to assess the role of TLR4 in the defense against Candida albicans infection. The outgrowth of C. albicans was 10-fold higher in TLR4-defective C3H/HeJ mice, compared with that in control C3H/HeN mice (P<.05). Production of tumor necrosis factor (TNF) and interleukin (IL)-1alpha and IL-1beta by mouse macrophages in response to C. albicans stimulation was not affected by TLR4, and the candidacidal capacities of the neutrophils and macrophages of C3H/HeJ mice were normal. In contrast, production of the CXC chemokines KC and macrophage inhibitory protein-2 was 40%-60% lower by the macrophages of C3H/HeJ mice (P<.05), which resulted in a 40% decrease in neutrophil recruitment to the site of infection. Candida-induced TNF and IL-1beta production by human peripheral blood mononuclear cells was significantly inhibited by blocking anti-TLR2 antibodies in vitro. In conclusion, TLR4-defective C3H/HeJ mice are more susceptible to C. albicans infection, and this is associated with impaired chemokine expression and neutrophil recruitment.
TL;DR: The relationship between a person's ABO histo-blood group type and the risk of NV infection and symptomatic disease after clinical challenge is investigated, demonstrating the first report demonstrating an association between a genetic factor and therisk ofNV infection and symptomomatic disease.
Abstract: Some people are resistant to Norwalk virus (NV) infection; however, the factor(s) responsible for resistance or susceptibility to NV infection has not been identified. This study investigated the relationship between a person's ABO histo-blood group type and the risk of NV infection and symptomatic disease after clinical challenge. ABO phenotypes were identified by using serum samples from volunteers who participated in an NV challenge study (n=51). Individuals with an O phenotype were more likely to be infected with NV (odds ratio [OR], 11.8; 95% confidence interval [CI], 1.3-103), whereas persons with a B histo-blood group antigen had decreased risk of infection (OR, 0.096; 95% CI, 0.16-0.56) and symptomatic disease (OR, 0; 95% CI, 0-0.999). This is the first report demonstrating an association between a genetic factor and the risk of NV infection and symptomatic disease.
TL;DR: Data suggest that PAFr-independent pathways are operative in the model, prompting further study of receptor interactions during pneumonia and bacteremia, and the model of lethal synergism will be a useful tool for exploring this and other mechanisms underlying viral-bacterial interactions.
Abstract: A lethal synergism exists between influenza virus and pneumococcus, which likely accounts for excess mortality from secondary bacterial pneumonia during influenza epidemics. Characterization of a mouse model of synergy revealed that influenza infection preceding pneumococcal challenge primed for pneumonia and led to 100% mortality. This effect was specific for viral infection preceding bacterial infection, because reversal of the order of administration led to protection from influenza and improved survival. The hypothesis that influenza up-regulates the platelet-activating factor receptor (PAFr) and thereby potentiates pneumococcal adherence and invasion in the lung was examined in the model. Groups of mice receiving CV-6209, a competitive antagonist of PAFr, had survival rates similar to those of control mice, and lung and blood bacterial titers increased during PAFr inhibition. These data suggest that PAFr-independent pathways are operative in the model, prompting further study of receptor interactions during pneumonia and bacteremia. The model of lethal synergism will be a useful tool for exploring this and other mechanisms underlying viral-bacterial interactions.
TL;DR: CMV serostatus remains associated with mortality; neutropenia due to ganciclovir administration and CMV disease explain the association with mortality among seropositive recipients; in D(+)/R(-) subjects, mortality appears to be associated with bacterial and fungal infection, indicating a possible immunomodulatory effect of primary CMV infection that was undetected despite intensive monitoring.
Abstract: The impact of cytomegalovirus (CMV) serostatus (seropositive [(+)] or seronegative [(-)]) of the donor (D) and recipient (R) on mortality after allogeneic non-T cell-depleted stem cell transplantation (SCT) in the era of preemptive therapy was assessed among 1750 patients by means of multivariable Cox regression models. In an analysis that included only pre-SCT variables, D(+)/R(+) and D(+)/R(-) patients had the highest risk for mortality. After neutropenia or the occurrence of CMV disease was controlled for, only D(+)/R(-) patients remained at a significantly higher risk for mortality. Mortality due to bacteremia or invasive fungal infection was higher among D(+)/R(-) (18.3%) than D(-)/R(-) (9.7%) patients (P <.001). Thus, CMV serostatus remains associated with mortality; neutropenia due to ganciclovir administration and CMV disease explain the association with mortality among seropositive recipients. However, in D(+)/R(-) subjects, mortality appears to be associated with bacterial and fungal infection, indicating a possible immunomodulatory effect of primary CMV infection that was undetected despite intensive monitoring.
TL;DR: Sequence studies of the nucleocapsid, fusion, and polymerase genes identified 2 main lineages of HMPV and cocirculation of both lineages during the same year.
Abstract: Human metapneumovirus (HMPV) was recently identified in The Netherlands and was linked to acute respiratory tract illness. In this study, 11 isolates from 10 patients with respiratory disease from Quebec, Canada, were tested by a reverse-transcriptase polymerase chain reaction based on the fusion protein gene. Identified sequences were consistent with HMPV. The patients were 2 months to 87 years of age (median age, 58 years) and presented with acute respiratory tract illness during the winter season. Sequence studies of the nucleocapsid, fusion, and polymerase genes identified 2 main lineages of HMPV and cocirculation of both lineages during the same year. These findings support a previous finding that HMPV is a human respiratory pathogen that merits further study.
TL;DR: A double-blind, randomized study involving 264 toddlers attending day care centers was conducted to document the effect of a 9-valent pneumococcal conjugate vaccine on the carriage rate of pneumococci, finding protection against carriage of S. pneumoniae serotypes 6B, 9V, 14, 19F, and 23F.
Abstract: A double-blind, randomized study involving 264 toddlers attending day care centers was conducted to document the effect of a 9-valent pneumococcal conjugate vaccine on the carriage rate of pneumococci. Of 3750 cultures done on nasopharyngeal samples obtained from subjects during a 2-year follow-up period after vaccination, 65% were positive for Streptococcus pneumoniae. In all age windows, the rate of carriage of vaccine-type pneumococci was lower among subjects who received the pneumococcal vaccine than among control subjects, because the acquisition rate was lower in the former group. The effect was most pronounced among subjects aged < or =36 months. The sample size enabled us to study protection against carriage of S. pneumoniae serotypes 6B, 9V, 14, 19F, and 23F; significant protection against all serotypes except 19F was seen in the pneumococcal-vaccine group. The rate of carriage of serotype 6A (not included in the vaccine) was also reduced significantly, but the rate of carriage of serotype 19A (not included in the vaccine) was not. The rate of carriage of non-vaccine-type pneumococci (excluding serotype 6A) was higher in the pneumococcal-vaccine group than in the control group.
TL;DR: Although varicella is most often a relatively benign and self-limited childhood illness, the disease can be associated with a variety of serious and potentially lethal complications in both immunocompetent and Immunocompromised persons.
Abstract: Varicella-zoster virus (VZV) is the etiologic agent of varicella (primary infection) and herpes zoster (reactivation of latent infection). Although varicella is most often a relatively benign and self-limited childhood illness, the disease can be associated with a variety of serious and potentially lethal complications in both immunocompetent and immunocompromised persons. One complication of varicella that appears to be increasing in frequency is serious bacterial soft tissue infections caused by group A streptococci. Issues related to management of varicella become especially complex when varicella involves pregnant women or susceptible neonates. Herpes zoster can be associated with a variety of neurologic complications, including a syndrome of delayed contralateral hemiparesis. Neurologic complications of herpes zoster, including chronic encephalitis, occur with increased frequency in AIDS patients. VZV retinitis is a potentially sight-threatening complication that occurs in both immunocompetent and immunocompromised persons. Current knowledge regarding pathogenesis and antiviral therapy is reviewed.
TL;DR: This large study in children with HUS underlines the rising importance of non-O157:H7 serotypes, and, despite increased public awareness, the number of patients remained unchanged.
Abstract: Hemolytic-uremic syndrome (HUS) is mainly associated with foodborne infections by Shiga toxin-producing Escherichia coli (STEC). From January 1997 through December 2000, 394 children with HUS were evaluated in a prospective multicenter surveillance study in Germany and Austria (incidences, 0.7/100,000 and 0.4/100,000 children <15 years old, respectively). Blood leukocytosis was associated with increased detection of STEC in stool cultures (P<.01) and a more severe disease course. Risk of death was associated with cerebral involvement (P<.01). Most strikingly, non-O157:H7 STEC were detected in 43% of stool cultures of patients with HUS: O26 was detected in 15%, sorbitol-fermenting O157:H(-) in 10%, O145 in 9%, O103 in 3%, and O111 in 43%. Patients with O157:H7 serotypes required dialysis for a longer time and had bloody diarrhea detected more frequently, compared with patients with non-O157:H7 serotypes (P<.05). This large study in children with HUS underlines the rising importance of non-O157:H7 serotypes, and, despite increased public awareness, the number of patients remained unchanged.
TL;DR: Ubiquitous behaviors among young IDUs, such as the forming of injecting or sexual partnerships and consequent sharing of needles and drug preparation equipment, are risk factors for HCV.
Abstract: The present study examined reasons for the high incidence of hepatitis C virus (HCV) infection among young injection drug users (IDUs). IDUs !30 years old who tested negative for HCV antibody were enrolled in a prospective cohort. Risk factors for seroconversionwere examined using time-dependent regression analyses: 48 of 195 IDUs seroconverted to HCV, for an incidence rate of 25.1/100 person-years (95% confidence interval, 18.7‐32.9/100 personyears). Independent risk factors included sharing needles with an HCV-infected sex partner (borderline statistical significance, ) or a person who was not a sex partner, sharing P p .11 nonsterile drug-preparation equipment, pooling money with another IDU to buy drugs, and exchanging sex for money. Ubiquitous behaviors among young IDUs, such as the forming of injecting or sexual partnerships and consequent sharing of needles and drug preparation equipment, are risk factors for HCV. InterventionstoreduceHCVtransmissionmustrecognize the importance of relationships on injecting risk. Hepatitis C virus (HCV) infection is highly prevalent (50%– 95%) among injection drug users (IDUs) and is transmitted via contaminated needles and syringes. Although the frequency of injecting with a needle and syringe previously used by someone else (“needle borrowing” or “needle sharing”) has decreased during the past 15 years [1–6], HCV incidence rates continue to be high [7–14].
TL;DR: Prospective screening for galactomannan allows earlier diagnosis of aspergillosis than do conventional diagnostic criteria, and detection was especially useful when patients were receiving steroid treatment or when coexisting conditions masked the diagnosis of invasive asperGillosis.
Abstract: Screening for galactomannan (GM) has been adopted by many European centers as part of the management plan for allogeneic stem cell transplant recipients. However, the temporal onset of GM antigenemia remains unknown. A series of allogeneic stem cell transplant recipients were monitored prospectively, and the relationship between antigenemia and other diagnostic triggers for initiation of antifungal therapy was analyzed. GM detection had a sensitivity of 94.4% and a specificity of 98.8%. Positive and negative predictive values were 94.4% and 98.8%, respectively. This statistical profile was better than that of other triggers, including unexplained fever, new pulmonary infiltrates, isolation of Aspergillus species, and abnormalities seen on computed tomography. Antigenemia preceded diagnosis on the basis of radiologic examination or Aspergillus isolation by 8 and 9 days in 80% and 88.8% of patients, respectively. Antigenemia preceded therapy in 83.3% of patients. Detection of GM was especially useful when patients were receiving steroid treatment or when coexisting conditions masked the diagnosis of invasive aspergillosis. Prospective screening for GM allows earlier diagnosis of aspergillosis than do conventional diagnostic criteria.
TL;DR: Mathematical modeling suggests that culling programs fail because of high incidence of infection and infectiousness, the insensitivity of the diagnostic test to detect infectious dogs, and time delays between diagnosis and culling.
Abstract: The elimination of seropositive dogs in Brazil has been used to control zoonotic visceral leishmaniasis but with little success. To elucidate the reasons for this, the infectiousness of 50 sentinel dogs exposed to natural Leishmania chagasi infection was assessed through time by xenodiagnosis with the sandfly vector, Lutzomyia longipalpis. Eighteen (43%) of 42 infected dogs became infectious after a median of 333 days in the field (105 days after seroconversion). Seven highly infectious dogs (17%) accounted for >80% of sandfly infections. There were positive correlations between infectiousness and anti-Leishmania immunoglobulin G, parasite detection by polymerase chain reaction, and clinical disease (logistic regression, r2=0.08-0.18). The sensitivity of enzyme-linked immunosorbent assay to detect currently infectious dogs was high (96%) but lower in the latent period (<63%), and specificity was low (24%). Mathematical modeling suggests that culling programs fail because of high incidence of infection and infectiousness, the insensitivity of the diagnostic test to detect infectious dogs, and time delays between diagnosis and culling.
TL;DR: The lack of TLR2 was associated with earlier death from meningitis, which was not due to sepsis but to reduced brain bacterial clearing, followed by increased intrathecal inflammation.
Abstract: Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacterial wall components. TLR2 function was investigated in a murine Streptococcus pneumoniae meningitis model in wild-type (wt) and TLR2-deficient (TLR2(-/-)) mice. TLR2(-/-) mice showed earlier time of death than wt mice (P<.02). Plasma interleukin-6 levels and bacterial numbers in blood and peripheral organs were similar for both strains. With ceftriaxone therapy, none of the wt but 27% of the TLR2(-/-) mice died (P<.04). Beyond 3 hours after infection, TLR2(-/-) mice had higher bacterial loads in brain than did wt mice, as assessed with luciferase-tagged S. pneumoniae by means of a Xenogen-CCD (charge-coupled device) camera. After 24 h, tumor necrosis factor activity was higher in cerebrospinal fluid of TLR2(-/-) than wt mice (P<.05) and was related to increased blood-brain barrier permeability (Evans blue staining, P<.02). In conclusion, the lack of TLR2 was associated with earlier death from meningitis, which was not due to sepsis but to reduced brain bacterial clearing, followed by increased intrathecal inflammation.
TL;DR: A novel genetic element, designated staphylococcal cassette chromosome mec (SCCmec) type IV, was found in 2 CA-MRSA isolates, and its relatively small size and presence in isolates of diverse genetic backgrounds suggest that it may spread among S. aureus isolates.
Abstract: Until recently, it has been unclear whether community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates represent the spread of hospital MRSA isolates into the community. In 2 CA-MRSA isolates, a novel genetic element, designated staphylococcal cassette chromosome mec (SCCmec) type IV, was found; it differs from SCCmec types I-III in its small size and absence of non-beta-lactam genetic-resistance determinants. To study the prevalence of type IV SCCmec, polymerase chain reaction characterization of SCCmec was performed on DNA from 12 CA-MRSA isolates. The 12 CA-MRSA isolates were from diverse genetic backgrounds, as evidenced by their stratification into 5 pulsed-field gel electrophoresis types, 4 coagulase types, and 2 ribotypes. Eleven of the 12 isolates contained the novel SCCmec type IV element. Ten were resistant only to beta-lactam antibiotics. SCCmec type IV is present on the genome of CA-MRSA isolates. Its relatively small size and presence in isolates of diverse genetic backgrounds suggest that it may spread among S. aureus isolates.
TL;DR: Future therapeutic strategies must target common mechanisms such as oxidative stress and dysregulation of intracellular calcium involved in virotoxin-mediated neurotoxicity involved in HIV infection of the nervous system.
Abstract: Human immunodeficiency virus (HIV) infection of the nervous system is unique when compared with other viral encephalitides. Neuronal cell loss occurs in the absence of neuronal infection. Viral proteins, termed virotoxins, are released from the infected glial cells that initiate a cascade of positive feedback loops by activating uninfected microglial cells and astrocytes. These activated cells release a variety of toxic substances that result in neuronal dysfunction and cell loss. The virotoxins act by a hit and run phenomenon. Thus, a transient exposure to the proteins initiates the neurotoxic cascade. High concentrations of these proteins likely occur in tight extracellular spaces where they may cause direct neurotoxicity as well. The emerging concepts in viral protein-induced neurotoxicity are reviewed as are the neurotoxic potential of each protein. Future therapeutic strategies must target common mechanisms such as oxidative stress and dysregulation of intracellular calcium involved in virotoxin-mediated neurotoxicity.
TL;DR: Patients with human immunodeficiency virus (HIV) type 1 infection who are starting to receive highly active antiretroviral therapy (HAART) and HBV-coinfected patients using 3TC should be considered, even if 3TC-resistant HIV strains develop.
Abstract: This retrospective cohort study investigated whether particular antiretroviral agents are associated with a higher risk for developing grade 4 liver enzyme elevations (LEEs) in patients with human immunodeficiency virus (HIV) type 1 infection who are starting to receive highly active antiretroviral therapy (HAART) Grade 4 LEE was defined as aminotransferase levels >10 times the upper limit of normal and >200 U above baseline levels A multivariate Cox model was used to identify risk factors The incidence of LEE was 63% No patients died of LEE consequences Risk factors were higher baseline alanine aminotransferase levels, chronic hepatitis B or C virus infection, antiretroviral therapy-naive patients undergoing their first HAART regimen, recent start of a regimen of nevirapine or high-dose ritonavir, and female sex In hepatitis B virus (HBV)-coinfected patients, discontinuing lamivudine (3TC) use was a risk factor In 97% of cases, >or=1 risk factor was present In HBV-coinfected patients using 3TC, continued use of 3TC should be considered, even if 3TC-resistant HIV strains develop