Showing papers in "The Journal of Infectious Diseases in 2005"
TL;DR: The rate of HIV transmission per coital act was highest during early-stage infection, which has implications for HIV prevention and for projecting the effects of antiretroviral treatment on HIV transmission.
Abstract: Background. We estimated rates of human immunodeficiency virus (HIV)‐1 transmission per coital act in HIV-discordant couples by stage of infection in the index partner. Methods. We retrospectively identified 235 monogamous, HIV-discordant couples in a Ugandan populationbased cohort. HIV transmission within pairs was confirmed by sequence analysis. Rates of transmission per coital act were estimated by the index partner’s stage of infection (recent seroconversion or prevalent or late-stage infection). The adjusted rate ratio of transmission per coital act was estimated by multivariate Poisson regression. Results. The average rate of HIV transmission was 0.0082/coital act (95% confidence interval [CI], 0.0039‐ 0.0150) within ∼2.5 months after seroconversion of the index partner; 0.0015/coital act within 6‐15 months after seroconversion of the index partner (95% CI, 0.0002‐0.0055); 0.0007/coital act (95% CI, 0.0005‐0.0010) among HIV-prevalent index partners; and 0.0028/coital act (95% CI, 0.0015‐0.0041) 6‐25 months before the death of the index partner. In adjusted models, early- and late-stage infection, higher HIV load, genital ulcer disease, and younger age of the index partner were significantly associated with higher rates of transmission. Conclusions. The rate of HIV transmission per coital act was highest during early-stage infection. This has implications for HIV prevention and for projecting the effects of antiretroviral treatment on HIV transmission. Model estimates suggest that the rate of heterosexual HIV-1 transmission per coital act follows a U-shaped curve, being highest during the postseroconversion period, lower during latency, and increasing with advancing disease [1‐4]. This is supported by findings that blood HIV load, which is higher during the postseroconversion period and during advanced disease, is the principal predictor of heterosexual transmission [5‐
1,310 citations
TL;DR: The vaccine did not prevent HIV-1 acquisition and there was no overall protective effect, but the efficacy trends in subgroups may provide clues for the development of effective immunization approaches.
Abstract: Background A vaccine is needed to prevent human immunodeficiency virus type 1 (HIV-1) infection. Methods A double-blind, randomized trial of a recombinant HIV-1 envelope glycoprotein subunit (rgp120) vaccine was conducted among men who have sex with men and among women at high risk for heterosexual transmission of HIV-1. Volunteers received 7 injections of either vaccine or placebo (ratio, 2 : 1) over 30 months. The primary end point was HIV-1 seroconversion over 36 months. Results A total of 5403 volunteers (5095 men and 308 women) were evaluated. The vaccine did not prevent HIV-1 acquisition: infection rates were 6.7% in 3598 vaccinees and 7.0% in 1805 placebo recipients; vaccine efficacy (VE) was estimated as 6% (95% confidence interval, -17% to 24%). There were no significant differences in viral loads, rates of antiretroviral-therapy initiation, or the genetic characteristics of the infecting HIV-1 strains between treatment arms. Exploratory subgroup analyses showed nonsignificant trends toward efficacy in preventing infection in the highest risk (VE, 43%; n=247) and nonwhite (VE, 47%; n=914) volunteers (P=.10, adjusted for multiple subgroup comparisons). Conclusions There was no overall protective effect. The efficacy trends in subgroups may provide clues for the development of effective immunization approaches.
955 citations
TL;DR: Non-O157 STEC can cause severe illness that is comparable to the illness caused by STEC O157, and Strains that produce Shiga toxin 2 are much more likely to cause HUS than are those that produceShiga toxin 1 alone.
Abstract: BACKGROUND Shiga toxin-producing Escherichia coli (STEC) O157:H7 is a well-recognized cause of bloody diarrhea and hemolytic-uremic syndrome (HUS). Non-O157 STEC contribute to this burden of illness but have been underrecognized as a result of diagnostic limitations and inadequate surveillance. METHODS Between 1983 and 2002, 43 state public health laboratories submitted 940 human non-O157 STEC isolates from persons with sporadic illnesses to the Centers for Diseases Control and Prevention reference laboratory for confirmation and serotyping. RESULTS The most common serogroups were O26 (22%), O111 (16%), O103 (12%), O121 (8%), O45 (7%), and O145 (5%). Non-O157 STEC infections were most frequent during the summer and among young persons (median age, 12 years; interquartile range, 3-37 years). Virulence gene profiles were as follows: 61% stx(1) but not stx(2); 22% stx(2) but not stx(1); 17% both stx(1) and stx(2); 84% intimin (eae); and 86% enterohemolysin (E-hly). stx(2) was strongly associated with an increased risk of HUS, and eae was strongly associated with an increased risk of bloody diarrhea. STEC O111 accounted for most cases of HUS and was also the cause of 3 of 7 non-O157 STEC outbreaks reported in the United States. CONCLUSIONS Non-O157 STEC can cause severe illness that is comparable to the illness caused by STEC O157. Strains that produce Shiga toxin 2 are much more likely to cause HUS than are those that produce Shiga toxin 1 alone. Improving surveillance will more fully elucidate the incidence and pathological spectrum of these emerging agents. These efforts require increased clinical suspicion, improved clinical laboratory isolation, and continued serotyping of isolates in public health laboratories.
692 citations
TL;DR: The role of social context in heterosexual networks that facilitate the spread of human immunodeficiency virus (HIV) infection and other sexually transmitted infections (STIs), particularly in relation to persistent racial disparities in rates of STIs in the United States is examined.
Abstract: African-Americans have the highest rates of human immunodeficiency virus (HIV) transmission, including heterosexual transmission, in the United States. Although numerous factors probably contribute to the extreme racial disparity, reasons for its persistence remain poorly explained. Mathematical modeling demonstrates that concurrent sexual partnerships speed transmission of HIV through sexual networks more effectively than does serial monogamy, for the same total number of sexual partners. This paper examines the evidence that the social and economic environment for many African-Americans discourages long-term monogamy and promotes concurrent sexual partnerships, which may, in turn, fuel the HIV epidemic in this population.
638 citations
TL;DR: Zygomycosis should be considered in immunosuppressed patients who develop sinusitis while receiving VRC prophylaxis, especially those with diabetes and malnutrition.
Abstract: Background. Anecdotal evidence suggests a rise in zygomycosis in association with voriconazole (VRC) use in immunosuppressed patients. Methods. We performed prospective surveillance of patients with zygomycosis (group A; n = 27) and compared them with contemporaneous patients with invasive aspergillosis (group B; n = 54) and with matched contemporaneous high-risk patients without fungal infection (group C; n = 54). We also performed molecular typing and in vitro susceptibility testing of Zygomycetes isolates. Results. Nearly all patients with zygomycosis either had leukemia (n = 14) or were allogeneic bone marrow transplant recipients (n = 13). The Zygomycetes isolates (74% of which were of the genus Rhizopus) had different molecular fingerprinting profiles, and all were VRC resistant. In multivariate analysis of groups A and C, VRC prophylaxis (odds ratio [OR], 10.37 [95% confidence interval {CI}], 2.76-38.97]; P = .001), diabetes (OR, 8.39 [95% CI, 2.04-34.35]; P = .003), and malnutrition (OR, 3.70 [95% CI, 1.03-13.27]; P = .045) were found to be independent risk factors for zygomycosis. Between patients with zygomycosis (after excluding 6 patients with mixed mold infections) and patients with aspergillosis, VRC prophylaxis (OR, 20.30 [95% CI, 3.85-108.15]; P = .0001) and sinusitis (OR, 76.72 [95% CI, 6.48-908.15]; P = .001) were the only factors that favored the diagnosis of zygomycosis. Conclusions. Zygomycosis should be considered in immunosuppressed patients who develop sinusitis while receiving VRC prophylaxis, especially those with diabetes and malnutrition.
626 citations
TL;DR: Strain surveillance helps to determine whether the most prevalent local strains are likely to be covered by the serotype antigens found in current vaccines, and identified globally (G9) or regionally (G5, G8, and P2A[6]) common serotypes not cover by the reassortant vaccines that have undergone efficacy trials.
Abstract: The development of rotavirus vaccines that are based on heterotypic or serotype-specific immunity has prompted many countries to establish programs to assess the disease burden associated with rotavirus infection and the distribution of rotavirus strains. Strain surveillance helps to determine whether the most prevalent local strains are likely to be covered by the serotype antigens found in current vaccines. After introduction of a vaccine, this surveillance could detect which strains might not be covered by the vaccine. Almost 2 decades ago, studies demonstrated that 4 globally common rotavirus serotypes (G1-G4) represent >90% of the rotavirus strains in circulation. Subsequently, these 4 serotypes were used in the development of reassortant vaccines predicated on serotype-specific immunity. More recently, the application of reverse-transcription polymerase chain reaction genotyping, nucleotide sequencing, and antigenic characterization methods has confirmed the importance of the 4 globally common types, but a much greater strain diversity has also been identified (we now recognize strains with at least 42 P-G combinations). These studies also identified globally (G9) or regionally (G5, G8, and P2A[6]) common serotype antigens not covered by the reassortant vaccines that have undergone efficacy trials. The enormous diversity and capacity of human rotaviruses for change suggest that rotavirus vaccines must provide good heterotypic protection to be optimally effective.
598 citations
TL;DR: Daptomycin was shown to interact in vitro with pulmonary surfactant, resulting in inhibition of antibacterial activity, which represents the first example of organ-specific inhibition of an antibiotic.
Abstract: The lipopeptide daptomycin has been approved for use in skin and skin-structure infections but has failed to meet statistical noninferiority criteria in a clinical trial for severe community-acquired pneumonia. Daptomycin exhibited an unusual pattern of activity in pulmonary animal models: efficacy in Staphylococcus aureus hematogenous pneumonia and inhalation anthrax but no activity against Streptococcus pneumoniae in simple bronchial-alveolar pneumonia. Daptomycin was shown to interact in vitro with pulmonary surfactant, resulting in inhibition of antibacterial activity. This effect was specific to daptomycin and consistent with its known mechanism of action. This represents the first example of organ-specific inhibition of an antibiotic.
486 citations
TL;DR: High baseline pVLs and substantial but imperfect levels of adherence were major predictors of antiretroviral resistance.
Abstract: Objective. The objective of this study was to systematically characterize the incidence and determinants of antiretroviral resistance in the HOMER (Highly Active Antiretroviral Therapy [HAART] Observational Medical Evaluation and Research) cohort of 1191 human immunodeficiency virus-infected, antiretroviral-naive adults initiating HAART in British Columbia, Canada.Methods. All plasma samples with plasma virus loads (pVLs) >1000 copies/mL collected during the first 30 months of follow-up were genotyped for drug resistance. The primary outcome measure was time to the first detection of major drug-resistance mutation(s). Cox proportional hazard regression was used to identify factors significantly associated with the detection of drug-resistance mutations.Results. Drug-resistance mutations were detected in 298 subjects (25%). Factors significantly associated with detection of drug-resistance mutations included high baseline pVL (multivariate hazard ratio [HR], 1.59; P < .001) and adherence (estimated using prescription-refill data and/or untimed plasma drug-concentration measurements). When compared with subjects with low (0%-<20%) prescription-refill percentages, subjects at an elevated risk of harboring drug-resistance mutations were those with relatively high but imperfect prescriptionrefill percentages (80%-<90%; multivariate HR, 4.15; P < .001) and those with essentially perfect (⩾95%) refill percentages but with 2 plasma drug concentrations below the steady-state trough concentration minus 1 standard deviation (multivariate HR, 4.57; P < .001). Initial use of nonnucleoside reverse-transcriptase inhibitor-based HAART was significantly associated with multiclass drug resistance (multivariate HR, 1.84; P = .001).Conclusion. High baseline pVLs and substantial but imperfect levels of adherence were major predictors of antiretroviral resistance.
445 citations
TL;DR: The increase in the risk of TB so soon after infection with HIV was unexpected, suggesting current predictive models of TB incidence underestimate the effect of HIV infection in areas where TB is endemic.
Abstract: The incidence of pulmonary TB was estimated in miners with and those without HIV infection ina retrospective cohort study. HIV test results were linked to routinely collected TB, demographic,andoccupationaldata. The rate ratio (RR) for the association between HIV status and TB was estimated by time since HIV se-roconversion, calendar period, and age.
435 citations
Utrecht University1, University of Foggia2, University of Bergen3, University of Milan4, Pierre-and-Marie-Curie University5, The Catholic University of America6, Katholieke Universiteit Leuven7, Sheba Medical Center8, Robert Koch Institute9, Athens State University10, Centre Hospitalier de Luxembourg11, University of Erlangen-Nuremberg12, Los Alamos National Laboratory13, Swedish Institute14, Carlos III Health Institute15, French Institute of Health and Medical Research16, Geneva College17, University of Vienna18, University of Belgrade19, University of Siena20
TL;DR: In this paper, the authors determined the baseline rate of drug resistance in 2208 therapy-naive patients recently and chronically infected with HIV-1 from 19 European countries during 1996-2002.
Abstract: BackgroundInfection with drug-resistant human immunodeficiency virus type 1 (HIV-1) can impair the response to combination therapy. Widespread transmission of drug-resistant variants has the disturbing potential of limiting future therapy options and affecting the efficacy of postexposure prophylaxispenta increase-spacing 1>MethodsWe determined the baseline rate of drug resistance in 2208 therapy-naive patients recently and chronically infected with HIV-1 from 19 European countries during 1996–2002ResultsIn Europe, 1 of 10 antiretroviral-naive patients carried viruses with ⩾1 drug-resistance mutation. Recently infected patients harbored resistant variants more often than did chronically infected patients (13.5% vs. 8.7%; P=.006). Non-B viruses (30%) less frequently carried resistance mutations than did subtype B viruses (4.8% vs. 12.9%; P<.01). Baseline resistance increased over time in newly diagnosed cases of non-B infection: from 2.0% (1/49) in 1996–1998 to 8.2% (16/194) in 2000–2001ConclusionsDrug-resistant variants are frequently present in both recently and chronically infected therapy-naive patients. Drug-resistant variants are most commonly seen in patients infected with subtype B virus, probably because of longer exposure of these viruses to drugs. However, an increase in baseline resistance in non-B viruses is observed. These data argue for testing all drug-naive patients and are of relevance when guidelines for management of postexposure prophylaxis and first-line therapy are updated
433 citations
TL;DR: The cumulative prevalence of HPV infection in sexually active adolescent women is extremely high, involves numerous HPV types, and frequently results in cervical dysplasia.
Abstract: Background—We performed a study to better characterize the natural history of genital human papillomavirus (HPV) infection in a cohort of closely followed adolescent women. Methods—A cohort of 60 adolescent women was followed over a 2.2-year period, on average. A median of 41.5 self-collected vaginal and clinician-obtained cervical swabs were obtained from each subject Results—HPV was detected in 45.3% of all adequate specimens, by use of a polymerase chain reaction/reverse blot strip assay. Oncogenic—or high-risk (HR)—HPV types were detected in 38.6% of specimens, and nononcogenic—or low-risk (LR)—types were detected in 19.6% of specimens. During the entire study period, 49 of 60 subjects tested positive for HPV (cumulative prevalence, 81.7%). The most frequently detected HR types were HPV types 52, 16, and 59. Infections with multiple HPV types were common. The median duration of persistence of a specific HPV type was 168 days, and HR types were more persistent than LR types. Abnormal cervical cytological results occurred in 37% of the adolescent women and were significantly associated with HR HPV infection. Conclusions—The cumulative prevalence of HPV infection in sexually active adolescent women is extremely high, involves numerous HPV types, and frequently results in cervical dysplasia. The marked upsurge in coital activity, pregnancy, and sexually transmitted infections (STIs) among middle-adolescent women justifies specific focus on this demographic group. Adolescents (10–19 years of age) and young adults (20–24 years of age) account for >65% of all reported STIs [1]. Human papillomavirus (HPV) is an STI of particular interest, because of its high prevalence rates and causal association with cervical malignancy. Our understanding of the epidemiology of HPV infection has grown and shifted immensely during the past 2 decades. It is well understood that infection of the genital tract with HPV leads to a range of pathologic states, including asymptomatic carriage of the virus, genital warts, cervical
TL;DR: Intraepithelial lesions are common early events among women with incident HPV infection, and the interval between incident HPV-16 or HPV-18 infection and biopsy-confirmed CIN grade 2-3 appears to be relatively short.
Abstract: Background To determine the potential value of human papillomavirus (HPV) vaccines, information concerning the incidence and duration of clinically important lesions is needed. Methods A total of 603 female university students were followed for a mean duration of 38.8 months. Triannual gynecologic examinations included cervical and vulvovaginal specimen collection for Pap and HPV DNA testing. Women with cytologic evidence of a high-grade squamous intraepithelial lesion (SIL) were referred for colposcopically directed biopsy. Results Among women with incident HPV infection, the 36-month cumulative incidence of cervical SILs found by cytologic testing (47.2%; 95% confidence interval [CI], 38.9%-56.4%) was higher than that of vaginal SILs (28.8%; 95% CI, 21.3%-38.2%). The median time to clearance of cervical and vaginal SILs was 5.5 and 4.7 months, respectively. Among women with incident HPV-16 or HPV-18 infection, the 36-month cumulative incidence of cervical intraepithelial neoplasia (CIN) grade 2 was 20.0% (95% CI, 10.8%-35.1%), and that of CIN grade 3 was 6.7% (95% CI, 2.5%-17.0%). The 36-month cumulative incidence of clinically ascertained genital warts among women with incident HPV-6 or HPV-11 infection was 64.2% (95% CI, 50.7%-77.4%). Conclusions Intraepithelial lesions are common early events among women with incident HPV infection, and the interval between incident HPV-16 or HPV-18 infection and biopsy-confirmed CIN grade 2-3 appears to be relatively short.
Canadian Science Centre for Human and Animal Health1, Defence Research and Development Canada2, Public Health Agency of Canada3, Toronto Public Health4, North York General Hospital5, University of Toronto6, Mount Sinai Hospital7, Women's College, Kolkata8, Toronto East General Hospital9, Ontario Ministry of Health and Long-Term Care10
TL;DR: These data provide the first experimental confirmation of viral aerosol generation by a patient with SARS, indicating the possibility of airborne droplet transmission, which emphasizes the need for adequate respiratory protection, as well as for strict surface hygiene practices.
Abstract: Severe acute respiratory syndrome (SARS) is characterized by a risk of nosocomial transmission; however, the risk of airborne transmission of SARS is unknown. During the Toronto outbreaks of SARS, we investigated environmental contamination in SARS units, by employing novel air sampling and conventional surface swabbing. Two polymerase chain reaction (PCR)-positive air samples were obtained from a room occupied by a patient with SARS, indicating the presence of the virus in the air of the room. In addition, several PCR-positive swab samples were recovered from frequently touched surfaces in rooms occupied by patients with SARS (a bed table and a television remote control) and in a nurses' station used by staff (a medication refrigerator door). These data provide the first experimental confirmation of viral aerosol generation by a patient with SARS, indicating the possibility of airborne droplet transmission, which emphasizes the need for adequate respiratory protection, as well as for strict surface hygiene practices.
TL;DR: Investigation in !
Abstract: The association between severe bronchiolitis and dual infection by human metapneumovirus (hMPV) and human respiratory syncytial virus (hRSV) was investigated in <2-year-old infants with bronchiolitis who were admitted to the hospital during the 2001-2002 winter season. hMPV in nasopharyngeal aspirate and/or cells and fluid collected by nonbronchoscopic bronchoalveolar lavage was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). hRSV was detected in nasopharyngeal aspirate and/or cells and fluid collected by nonbronchoscopic bronchoalveolar lavage by enzyme immunoassay, tissue culture, and RT-PCR. Dual infection with hMPV and hRSV confers a 10-fold increase in relative risk (RR) of admission to a pediatric intensive-care unit for mechanical ventilation (RR, 10.99 [95% confidence interval, 5.0-24.12]; P<.001, by Fisher exact test). Dual infection by hMPV and hRSV is associated with severe bronchiolitis.
TL;DR: HCV serostatus did not affect the risk of HIV-1 disease progression, but therisk of liver disease-related deaths was markedly increased in HCV-seropositive patients.
Abstract: Objective. To assess hepatitis C virus (HCV) antibody prevalence in the EuroSIDA cohort, along with survival, human immunodeficiency virus (HIV)-1 disease progression, virologic response (plasma HIV -1 RNA load of<500 copies/mL), and CD4 cell count recovery by HCV serostatus in patients initiating highly active antiretroviral therapy (HAART). Results. HCV serostatus at or before enrollment was available for 5957 patients; 1960 (33%) and 3997 (67%) were HCV seropositive and seronegative, respectively. No association between an increased incidence of acquired immunodeficiency syndrome-defining illnesses or death and HCV serostatus was seen after adjustment for other prognostic risk factors known at baseline (adjusted incidence rate ratio [IRR], 0.97 [95% confidence interval {CI}, 0.81-1.16]). However, there was a large increase in the incidence of liver disease-related deaths in HCV-seropositive patients in adjusted models (IRR, 11.71 [95% CI, 6.42-21.34]). Among 2260 patients of known HCV serostatus initiating HAART, after adjustment, there was no significant difference between HCV-seropositive and -seronegative patients with respect to virologic response (relative hazard [RH], 1.13 [95% CI, 0.84-1.51]) and immunologic response, whether measured as a ≥50% increase (RH, 0.94 [95% CI, 0.77-1.16]) or a ≥50 cells/μL increase (RH, 0.92 [95% CI, 0.77-1.11]) in CD4 cell count after HAART initiation. Conclusions. HCV serostatus did not affect the risk of HIV-1 disease progression, but the risk of liver disease-related deaths was markedly increased in HCV-seropositive patients. The overall virologic and immunologic responses to HAART were not affected by HCV serostatus.
TL;DR: A matched case-control study determined that foods containing green onions, which were eaten by 38 (95%) of 40 case patients compared with 30 (50%) of 60 control subjects, were associated with illness and more sensitive methods are needed to detect foodborne hepatitis A.
Abstract: Forty-three cases of serologically confirmed hepatitis A occurred among individuals who ate at restaurant A in Ohio in 1998. Serum samples from all restaurant A employees who worked during the exposure period were negative for IgM antibodies to hepatitis A virus (HAV). A matched case-control study determined that foods containing green onions, which were eaten by 38 (95%) of 40 case patients compared with 30 (50%) of 60 control subjects, were associated with illness (matched odds ratio, 12.7; 95% confidence interval, 2.6-60.8). Genetic sequences of viral isolates from 14 case patients were identical to each other and to those of viral isolates from 3 patients with cases of hepatitis A acquired in Mexico. Although the implicated green onions, which could have come from one of 2 Mexican farms or from a Californian farm, were widely distributed, no additional green onion-associated cases were detected. More sensitive methods are needed to detect foodborne hepatitis A. A better understanding of how HAV might contaminate raw produce would aid in developing prevention strategies.
TL;DR: Overall, HPV acquisition predominated at younger ages, whereas persistent infections gradually became more prominent with age; this latter tendency supports the utility of HPV screening in older women.
Abstract: Background. Cross-sectional human papillomavirus (HPV) DNA prevalence peaks at young ages reflecting sexual acquisition and typically rapid clearance. In some populations HPV prevalence demonstrates a second peak in older women. Longitudinal data may help to explain this second peak. Methods. We followed a population-based cohort of 7237 women in Guanacaste Costa Rica in which we had previously observed a second peak in the baseline HPV prevalence in older women. We tested for >40 HPV types by polymerase chain reaction. We analyzed age-specific patterns of acquisition and persistence 5-7 years after enrollment for individual HPV types. Results. At enrollment and follow-up cross-sectional data revealed U-shaped age-specific HPV prevalence curves for virtually every type with higher prevalences in the younger and older women than in the middle-aged women. Prospectively acquisition of types decreased significantly as women aged (P(-Trend)<.05 for both) with the highest peak in young women and a secondary minor peak in older women. Type-specific persistence of HPV increased with age (P(-Trend)<.0001). Overall HPV acquisition predominated at younger ages whereas persistent infections gradually became more prominent with age (P(-Trend)<.0001). Conclusions. Newly apparent infections decreased whereas persistence increased with age; this latter tendency supports the utility of HPV screening in older women. (authors)
TL;DR: If duration of membrane rupture and internal fetal monitoring are confirmed to be associated with transmission, interventions may be possible to decrease the risk of transmission.
Abstract: P ! .05 HCV RNA negative). In multivariate analysis restricted to HCV RNA‐positive mothers, membrane rupture 6 h (odds ratio [OR], 9.3 [95% CI, 1.5‐179.7]) and internal fetal monitoring (OR, 6.7 [95% CI, 1.1‐35.9]) were associated with transmission of HCV to infants. Conclusion. If duration of membrane rupture and internal fetal monitoring are confirmed to be associated with transmission, interventions may be possible to decrease the risk of transmission.
TL;DR: Evidence of a novel human coronavirus, designated “New Haven coronav virus” (HCoVNH), in respiratory secretions from a 6-month-old infant with classic Kawasaki disease is identified and data suggest that HCoV-NH infection is associated with Kaw Osaka disease.
Abstract: Kawasaki disease is a systemic vasculitis of childhood; its etiology is unknown. We identified evidence of a novel human coronavirus, designated "New Haven coronavirus" (HCoV-NH), in respiratory secretions from a 6-month-old infant with classic Kawasaki disease. To further investigate the possible association between HCoV-NH infection and Kawasaki disease, we conducted a case-control study. Specimens of respiratory secretions from 8 (72.7%) of 11 children with Kawasaki disease and from 1 (4.5%) of 22 control subjects (children without Kawasaki disease matched by age and the time the specimens were obtained) tested positive for HCoV-NH by reverse-transcriptase polymerase chain reaction (Mantel-Haenszel matched odds ratio, 16.0 [95% confidence interval, 3.4-74.4]; P=.0015). These data suggest that HCoV-NH infection is associated with Kawasaki disease.
TL;DR: The bimodal age pattern of HPV infection in Guanacaste and the sexually transmitted nature of both oncogenic and nononcogenic HPV types were confirmed.
Abstract: Background Detailed epidemiologic studies of cervical type-specific human papillomavirus (HPV) infection in large populations are scarce. Methods We recruited a population-based cohort in Guanacaste, Costa Rica. Participants were interviewed, screened for cervical neoplasia, and tested for >40 HPV types by use of MY09/11 L1 consensus primer polymerase chain reaction. We estimated the risk factors for infection and the associations between type-specific HPV infections and cervical intraepithelial neoplasia (CIN) and cancer in 8514 sexually active women who had not undergone a hysterectomy. Results The overall HPV prevalence was 26.5%. The most common type was HPV-16 (3.6% of the population). HPV prevalence showed a U-shaped age-specific curve. Sexual behaviors were the main determinants of oncogenic and nononcogenic infections; age at first sexual intercourse was not independently associated with infection. Barrier contraceptive use was somewhat protective against infection. Oncogenic infections were strongly associated with risk of all grades of CIN and of cancer. Types 16, 18, and 58 were the most common in women diagnosed with CIN3 and cancer. Except for those that included HPV-16, multiple-type infections were associated with an increased risk (compared with that for single-type infections) of all grades of CIN and of cancer. Conclusions We confirmed the bimodal age pattern of HPV infection in Guanacaste and the sexually transmitted nature of both oncogenic and nononcogenic HPV types.
TL;DR: An follow-up clinical trial in Zanzibar points to 86N as a potential marker of lumefantrine resistance in vivo, while suggesting that Coartem is not robust enough to avoid selection of resistance-associated mutations in some malarial settings.
Abstract: Artemisinin derivative-based combination therapy is expected to suppress the development of Plasmodium falciparum drug resistance in Africa. We have performed an artemether-lumefantrine (Coartem; Novartis) follow-up clinical trial in Zanzibar, in which pfcrt K76T and pfmdr1 N86Y frequencies were determined before drug administration and in all recurrent parasites during a follow-up period of 42 days. A significant increase in pfmdr1 86N was observed after exposure to the drug. This points to 86N as a potential marker of lumefantrine resistance in vivo, while suggesting that Coartem is not robust enough to avoid selection of resistance-associated mutations in some malarial settings.
TL;DR: Despite inducing a complex, robust immune response, the vaccine was unable to reduce the incidence of HIV-1, and two interpretations of the correlative results are that the levels of antibodies caused both an increased (low responders) and decreased (high responders) risk of HIV -1 acquisition.
Abstract: Background. An objective of the first efficacy trial of a candidate vaccine containing recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein 120 (rgp120) antigens was to assess correlations between antibody responses to rgp120 and the incidence of HIV-1 infection. Methods. Within the randomized trial (for vaccinees, n = 3598; for placebo recipients, n = 1805), binding and neutralizing antibody responses to rgp120 were quantitated. A case-cohort design was used to study correlations between antibody levels and HIV-1 incidence. Results. Peak antibody levels were significantly inversely correlated with HIV-1 incidence. The relative risk (RR) of infection was 0.63 (95% confidence interval, 0.45-0.89) per log10 higher neutralization titer against HIV-1MN, and the RRs of infection for second-, third-, and fourth-quartile responses of antibody blocking of gp120 binding to soluble CD4 versus first-quartile responses (the lowest responses) were 0.35, 0.28, and 0.22, respectively. Conclusions. Despite inducing a complex, robust immune response, the vaccine was unable to reduce the incidence of HIV-1. Two interpretations of the correlative results are that the levels of antibodies (i) caused both an increased (low responders) and decreased (high responders) risk of HIV-1 acquisition or (ii) represented a correlate of susceptibility to HIV-1 but had no causal effect on susceptibility. Although the data cannot definitively discriminate between these 2 explanations, (ii) appears to be more likely.
TL;DR: Virtual identity in the 36-kb region present in contemporary serotypes M1 and M12 isolates suggests that a serotype M12 strain served as the donor of this region and was associated with significantly increased production of SLO and NADase.
Abstract: To better understand the molecular events involved in the origin of new pathogenic bacteria, we studied the evolution of a highly virulent clone of serotype M1 group A Streptococcus (GAS). Genomic, DNA-DNA microarray, and single-nucleotide polymorphism analyses indicated that this clone evolved through a series of horizontal gene transfer events that involved (1) the acquisition of prophages encoding streptococcal pyrogenic exotoxin A and extracellular DNases and (2) the reciprocal recombination of a 36-kb chromosomal region encoding the extracellular toxins NAD+-glycohydrolase (NADase) and streptolysin O (SLO). These gene transfer events were associated with significantly increased production of SLO and NADase. Virtual identity in the 36-kb region present in contemporary serotype M1 and M12 isolates suggests that a serotype M12 strain served as the donor of this region. Multiple horizontal gene transfer events were a crucial factor in the evolutionary origin and emergence of a very abundant contemporary clone of serotype M1 GAS.
TL;DR: Serotype 19A is, at present, the most important cause of IPD by replacement serotypes, and it is increasingly drug resistant, and some of the increase in rates of infection with serotypes may be due to serotype switching within certain vaccine type strains.
Abstract: Background. The introduction of the 7-valent conjugate pneumococcal vaccine (PCV7) in children may result in serotype replacement. We estimated the rate of increase of invasive pneumococcal disease (IPD) caused by serotype 19A in children <5 years old and determined the genetic composition of these isolates. Methods. Cases of IPD between July 1999 and June 2004 were identified through the Active Bacterial Core Surveillance. Serotype 19A isolates obtained from children <5 years old between January 2003 and June 2004 were characterized by serotyping, antibiotic susceptibility testing, and pulsed-field gel electrophoresis (PFGE). Select isolates representing homologous PFGE clusters were subjected to multilocus sequence typing, and eBURST was used to delineate clonal groups. Results. Between July 1999 and June 2004, the overall rate of IPD decreased from 23.3 to 13.1 cases/100,000 population (P<.00001). In children <5 years old, the rate decreased from 88.7 to 22.4 cases/100,000 population (P<.00001), whereas the rate in persons ≥5 years old decreased from 18.4 to 12.4 cases/100,000 population (P<.0001). The rate of serotype 19A IPD in children <5 years old increased significantly from 2.6 cases/100,000 population in 1999-2000 to 6.5 cases/100,000 population in 2003-2004; this was accompanied by significant increases in penicillin nonsusceptibility (P =.008) and multidrug resistance (P =.002) among serotype 19A isolates. As was observed during the pre-PCV7 era, clonal complex (CC) 199 predominated within serotype 19A, representing ∼70% of invasive serotype 19A isolates from children <5 years old during 2003-2004. New serotype 19A genotypes were observed during 2003-2004, including 6 CCs that were not found among pneumococcal serotype 19A isolates during surveillance in 1999. Conclusion. Serotype 19A is, at present, the most important cause of IPD by replacement serotypes, and it is increasingly drug resistant. CC199 is the predominant CC among type 19A serotypes in children <5 years old. Our data suggest that some of the increase in rates of infection with serotype 19A may be due to serotype switching within certain vaccine type strains.
TL;DR: The present data are useful in that they confirm the mechanisms by which HbAS confers protection against malaria and shed light on the relationships between Hbas, malaria, and other childhood diseases.
Abstract: Background: The gene for sickle hemoglobin (Hbs) is a prime example of natural selection. It is generally believed that its current prevalence in many tropical populations reflects selection for the carrier form (sickle cell trait [HbAS]) through a survival advantage against death from malaria. Nevertheless, >50 years after this hypothesis was first proposed, the epidemiological description of the relationships between HbAS, malaria, and other common causes of child mortality remains incomplete. Methods: We studied the incidence of falciparum malaria and other childhood diseases in 2 cohorts of children living on the coast of Kenya. Results: The protective effect of HbAS was remarkably specific for falciparum malaria, having no significant impact on any other disease. HbAS had no effect on the prevalence of symptomless parasitemia but was 50% protective against mild clinical malaria, 75% protective against admission to hospital for malaria, and almost 90% protective against severe or complicated malaria. The effect of HbAS on episodes of clinical malaria was mirrored in its effect on parasite densities during such episodes. Conclusions: The present data are useful in that they confirm the mechanisms by with HbAS confers protection against malaria and shed light on the relationships between HbAS, malaria, and other childhood diseases.
TL;DR: These data provide the first evidence, to the authors' knowledge, of an important role of the vagus nerve in regulating the innate immune response to a severe bacterial infection.
Abstract: Background The nervous system, through the vagus nerve, can down-regulate inflammation in vivo by decreasing the release of tumor necrosis factor- alpha by endotoxin-stimulated macrophages. This anti-inflammatory effect is mediated by an interaction between acetylcholine, the principal neurotransmitter of the vagus nerve, and cholinergic nicotinic acetylcholine receptors on macrophages. Methods We determined the role of this "cholinergic anti-inflammatory pathway" during septic peritonitis induced in mice by intraperitoneal injection of live Escherichia coli. Septic peritonitis was preceded by inhibition of the cholinergic anti-inflammatory pathway by unilateral cervical vagotomy, by stimulation of this pathway by pretreatment of mice with nicotine, or by a combination of both interventions. Results Initial cytokine release during septic peritonitis was enhanced after previous vagotomy and was decreased after nicotine pretreatment, independently of the integrity of the vagus nerve. Further study established that vagotomy before septic peritonitis resulted in an enhanced influx of neutrophils and a marked increase in proinflammatory cytokine levels and liver damage. Conversely, nicotine pretreatment strongly decreased cell influx, proinflammatory cytokine levels, and liver damage, whereas bacterial clearance and survival were impaired. Discussion These data provide the first evidence, to our knowledge, of an important role of the vagus nerve in regulating the innate immune response to a severe bacterial infection.
TL;DR: Patients with antimicrobial-resistant nontyphoidal Salmonella infection were more likely to have bloodstream infection and to be hospitalized than were patients with pansusceptible infection.
Abstract: Background Nontyphoidal Salmonella is a leading cause of foodborne illness. Few studies have explored the health consequences of antimicrobial-resistant Salmonella. Methods The National Antimicrobial Resistance Monitoring System (NARMS) performs susceptibility testing on nontyphoidal Salmonella isolates. The Foodborne Diseases Active Surveillance Network (FoodNet) ascertains outcomes for patients with culture-confirmed Salmonella infection, in 9 states, each of which participates in NARMS. We analyzed the frequency of bloodstream infection and hospitalization among patients with resistant infections. Isolates defined as resistant to a clinically important agent were resistant to 1 or more of the following agents: ampicillin, ceftriaxone, ciprofloxacin, gentamicin, and/or trimethoprim-sulfamethoxazole. Results During 1996-2001, NARMS received 7370 serotyped, nontyphoidal Salmonella isolates from blood or stool. Bloodstream infection occurred more frequently among patients infected with an isolate resistant to > or =1 clinically important agent (adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2-2.1), compared with patients with pansusceptible infection. During 1996-2001, FoodNet staff ascertained outcomes for 1415 patients who had isolates tested in NARMS. Hospitalization with bloodstream infection occurred more frequently among patients infected with an isolate resistant to > or =1 clinically important agent (adjusted OR, 3.1; 95% CI, 1.4-6.6), compared with patients with pansusceptible infection. Conclusions Patients with antimicrobial-resistant nontyphoidal Salmonella infection were more likely to have bloodstream infection and to be hospitalized than were patients with pansusceptible infection. Mitigation of antimicrobial resistance in Salmonella will likely benefit human health.
TL;DR: Treatment <6 months after seroconversion may facilitate long-term control of cellular reservoirs that maintain HIV-1 infection during treatment, suggesting that patients in whom virologic suppression is achieved with highly active antiretroviral therapy (HAART) retain long-lived cellular reservoirs.
Abstract: Patients in whom virologic suppression is achieved with highly active antiretroviral therapy (HAART) retain long-lived cellular reservoirs of human immunodeficiency virus type 1 (HIV-1); this retention is an obstacle to sustained control of infection. To assess the impact that initiating treatment during primary HIV-1 infection has on this cell population, we analyzed the decay kinetics of HIV-1 DNA and of infectivity associated with cells activated ex vivo in 27 patients who initiated therapy before or <6 months after seroconversion and in whom viremia was suppressed to <50 copies/mL. The clearance rates of cellular reservoirs could not be distinguished by these techniques (median half-life, 20 weeks) during the first year of HAART. The clearance of HIV-1 DNA slowed significantly during the subsequent 3 years of treatment (median half-life, 70 weeks), consistent with heterogeneous cellular reservoirs being present. Total cell-associated infectivity (CAI) after 1 year of treatment was undetectable (<0.07 infectious units/million cells [IUPM]) in most patients initiating treatment during primary infection either before (9/9) or <6 months after (6/8) seroconversion. In contrast, all 17 control patients who initiated HAART during chronic infection retained detectable CAI after 3-6 years of treatment (median reservoir size, 1.1 IUPM; P<.0005). These results suggest that treatment <6 months after seroconversion may facilitate long-term control of cellular reservoirs that maintain HIV-1 infection during treatment.
TL;DR: Human serum samples after immunization with MF59 or nonadjuvanted A/duck/Singapore/97 (H5N3) vaccine were tested for antibody to 1997-2004 human H5N1 viruses and findings have implications for the rational design of pandemic vaccines against influenza H5.
Abstract: Antigenically well-matched vaccines against highly pathogenic avian influenza H5N1 viruses are urgently required. Human serum samples after immunization with MF59 or nonadjuvanted A/duck/Singapore/97 (H5N3) vaccine were tested for antibody to 1997-2004 human H5N1 viruses. Antibody responses to 3 doses of nonadjuvanted vaccine were poor and were higher after MF59-adjuvanted vaccine, with seroconversion rates to A/HongKong/156/97, A/HongKong/213/03, A/Thailand/16/04, and A/Vietnam/1203/04 of 100% (P < .0001), 100% (P < .0001), 71% (P = .0004), and 43% (P = .0128) in 14 subjects, respectively, compared with 27%, 27%, 0%, and 0% in 11 who received nonadjuvanted vaccine. These findings have implications for the rational design of pandemic vaccines against influenza H5.
TL;DR: Recommendations to provide pneumococcal vaccine to persons in these at-risk groups are supported and the need for better prevention strategies for immunocompromised persons is underscore.
Abstract: Pneumococcal disease is more frequent and more deadly in persons with certain comorbidities. We used 1999 and 2000 data from the Active Bacterial Core surveillance (ABCs) and the National Health Interview Survey (NHIS) to determine rates of invasive pneumococcal disease in healthy adults (> or =18 years old) and in adults with various high-risk conditions. The risks of invasive pneumococcal disease in persons with specific chronic illnesses was compared with that in healthy adults, controlling for age, race, and the other chronic illnesses. Overall incidence rates, in cases/100,000 persons, were 8.8 in healthy adults, 51.4 in adults with diabetes, 62.9 in adults with chronic lung disease, 93.7 in adults with chronic heart disease, and 100.4 in adults who abused alcohol. Among the high-risk groups evaluated, risk was highest in adults with solid cancer (300.4), HIV/AIDS (422.9), and hematological cancer (503.1). Incidence rates increased with advancing age in adults with chronic lung disease, diabetes, and solid cancer. Black adults had higher incidence rates than white adults, both in healthy adults and in adults with chronic illnesses. These data support recommendations to provide pneumococcal vaccine to persons in these at-risk groups and underscore the need for better prevention strategies for immunocompromised persons.