Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 50 Records) |
Query Trace: Tam K[original query] |
---|
Reducing hospitalizations and multidrug-resistant organisms via regional decolonization in hospitals and nursing homes
Gussin GM , McKinnell JA , Singh RD , Miller LG , Kleinman K , Saavedra R , Tjoa T , Gohil SK , Catuna TD , Heim LT , Chang J , Estevez M , He J , O'Donnell K , Zahn M , Lee E , Berman C , Nguyen J , Agrawal S , Ashbaugh I , Nedelcu C , Robinson PA , Tam S , Park S , Evans KD , Shimabukuro JA , Lee BY , Fonda E , Jernigan JA , Slayton RB , Stone ND , Janssen L , Weinstein RA , Hayden MK , Lin MY , Peterson EM , Bittencourt CE , Huang SS . Jama 2024 IMPORTANCE: Infections due to multidrug-resistant organisms (MDROs) are associated with increased morbidity, mortality, length of hospitalization, and health care costs. Regional interventions may be advantageous in mitigating MDROs and associated infections. OBJECTIVE: To evaluate whether implementation of a decolonization collaborative is associated with reduced regional MDRO prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California. EXPOSURES: Chlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP). MAIN OUTCOMES AND MEASURES: Baseline and end of intervention MDRO point prevalence among participating facilities; incident MDRO (nonscreening) clinical cultures among participating and nonparticipating facilities; and infection-related hospitalizations and associated costs and deaths among residents in participating and nonparticipating nursing homes (NHs). RESULTS: Thirty-five facilities (16 hospitals, 16 NHs, 3 long-term acute care hospitals [LTACHs]) adopted the intervention. Comparing decolonization with baseline periods among participating facilities, the mean (SD) MDRO prevalence decreased from 63.9% (12.2%) to 49.9% (11.3%) among NHs, from 80.0% (7.2%) to 53.3% (13.3%) among LTACHs (odds ratio [OR] for NHs and LTACHs, 0.48; 95% CI, 0.40-0.57), and from 64.1% (8.5%) to 55.4% (13.8%) (OR, 0.75; 95% CI, 0.60-0.93) among hospitalized patients in CP. When comparing decolonization with baseline among NHs, the mean (SD) monthly incident MDRO clinical cultures changed from 2.7 (1.9) to 1.7 (1.1) among participating NHs, from 1.7 (1.4) to 1.5 (1.1) among nonparticipating NHs (group × period interaction reduction, 30.4%; 95% CI, 16.4%-42.1%), from 25.5 (18.6) to 25.0 (15.9) among participating hospitals, from 12.5 (10.1) to 14.3 (10.2) among nonparticipating hospitals (group × period interaction reduction, 12.9%; 95% CI, 3.3%-21.5%), and from 14.8 (8.6) to 8.2 (6.1) among LTACHs (all facilities participating; 22.5% reduction; 95% CI, 4.4%-37.1%). For NHs, the rate of infection-related hospitalizations per 1000 resident-days changed from 2.31 during baseline to 1.94 during intervention among participating NHs, and from 1.90 to 2.03 among nonparticipating NHs (group × period interaction reduction, 26.7%; 95% CI, 19.0%-34.5%). Associated hospitalization costs per 1000 resident-days changed from $64 651 to $55 149 among participating NHs and from $55 151 to $59 327 among nonparticipating NHs (group × period interaction reduction, 26.8%; 95% CI, 26.7%-26.9%). Associated hospitalization deaths per 1000 resident-days changed from 0.29 to 0.25 among participating NHs and from 0.23 to 0.24 among nonparticipating NHs (group × period interaction reduction, 23.7%; 95% CI, 4.5%-43.0%). CONCLUSIONS AND RELEVANCE: A regional collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in CP was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths. |
Two rotavirus outbreaks caused by genotype G2P[4] at large retirement communities: cohort studies.
Cardemil CV , Cortese MM , Medina-Marino A , Jasuja S , Desai R , Leung J , Rodriguez-Hart C , Villarruel G , Howland J , Quaye O , Tam KI , Bowen MD , Parashar UD , Gerber SI . Ann Intern Med 2012 157 (9) 621-31 BACKGROUND: Outbreaks of rotavirus gastroenteritis in elderly adults are reported infrequently but are often caused by G2P[4] strains. In 2011, outbreaks were reported in 2 Illinois retirement facilities. OBJECTIVE: To implement control measures, determine the extent and severity of illness, and assess risk factors for disease among residents and employees. DESIGN: Cohort studies using surveys and medical chart abstraction. SETTING: Two large retirement facilities in Cook County, Illinois. PATIENTS: Residents and employees at both facilities and community residents with rotavirus disease. MEASUREMENTS: Attack rates, hospitalization rates, and rotavirus genotype. RESULTS: At facility A, 84 of 324 residents (26%) were identified with clinical or laboratory-confirmed rotavirus gastroenteritis (median age, 84 years) and 11 (13%) were hospitalized. The outbreak lasted 7 weeks. At facility B, 90 case patients among 855 residents (11%) were identified (median age, 88 years) and 19 (21%) were hospitalized. The facility B outbreak lasted 9.3 weeks. Ill employees were identified at both locations. In each facility, attack rates seemed to differ by residential setting, with the lowest rates among those in more separated settings or with high baseline level of infection control measures. The causative genotype for both outbreaks was G2P[4]. Some individuals shed virus detected by enzyme immunoassay or genotyping reverse transcription polymerase chain reaction for at least 35 days. G2P[4] was also identified in 17 of 19 (89%) samples from the older adult community but only 15 of 40 (38%) pediatric samples. LIMITATION: Medical or cognitive impairment among residents limited the success of some interviews. CONCLUSION: Rotavirus outbreaks can occur among elderly adults in residential facilities and can result in considerable morbidity. Among older adults, G2P[4] may be of unique importance. Health professionals should consider rotavirus as a cause of acute gastroenteritis in adults. PRIMARY FUNDING SOURCE: None. |
Standard-dose versus MF59-adjuvanted, high-dose or recombinant-hemagglutinin influenza vaccine immunogenicity in older adults: comparison of A(H3N2) antibody response by prior season's vaccine status
Zhong S , Ng TWY , Skowronski DM , Iuliano AD , Leung NHL , Perera Rapm , Ho F , Fang VJ , Tam YH , Ip DKM , Havers FG , Fry AM , Aziz-Baumgartner E , Barr IG , Peiris M , Thompson MG , Cowling BJ . J Infect Dis 2023 BACKGROUND: Annual influenza vaccination is recommended for older adults but repeated vaccination with standard-dose influenza vaccine has been linked to reduced immunogenicity and effectiveness, especially against A(H3N2) viruses. METHODS: Community-dwelling Hong Kong adults aged 65-82 years were randomly allocated to receive 2017/18 standard-dose quadrivalent, MF59-adjuvanted trivalent, high-dose trivalent, and recombinant-HA quadrivalent vaccination. Antibody response to unchanged A(H3N2) vaccine antigen was compared among participants with and without self-reported prior year (2016/17) standard-dose vaccination. RESULTS: Mean fold rise (MFR) in antibody titers from Day 0 to Day 30 by hemagglutination inhibition and virus microneutralization assays were lower among 2017/18 standard-dose and enhanced vaccine recipients with (range, 1.7-3.0) vs. without (range, 4.3-14.3) prior 2016/17 vaccination. MFR was significantly reduced by about one half to four fifths for previously vaccinated recipients of standard-dose and all three enhanced vaccines (β range, 0.21-0.48). Among prior-year vaccinated older adults, enhanced vaccines induced higher 1.43 to 2.39-fold geometric mean titers and 1.28 to 1.74-fold MFR vs. standard-dose vaccine by microneutralization assay. CONCLUSIONS: In the context of unchanged A(H3N2) vaccine strain, prior-year vaccination was associated with reduced antibody response among both standard-dose and enhanced influenza vaccine recipients. Enhanced vaccines improved antibody response among older adults with prior-year standard-dose vaccination. |
Decolonization in nursing homes to prevent infection and hospitalization
Miller LG , McKinnell JA , Singh RD , Gussin GM , Kleinman K , Saavedra R , Mendez J , Catuna TD , Felix J , Chang J , Heim L , Franco R , Tjoa T , Stone ND , Steinberg K , Beecham N , Montgomery J , Walters D , Park S , Tam S , Gohil SK , Robinson PA , Estevez M , Lewis B , Shimabukuro JA , Tchakalian G , Miner A , Torres C , Evans KD , Bittencourt CE , He J , Lee E , Nedelcu C , Lu J , Agrawal S , Sturdevant SG , Peterson E , Huang SS . N Engl J Med 2023 389 (19) 1766-1777 BACKGROUND: Nursing home residents are at high risk for infection, hospitalization, and colonization with multidrug-resistant organisms. METHODS: We performed a cluster-randomized trial of universal decolonization as compared with routine-care bathing in nursing homes. The trial included an 18-month baseline period and an 18-month intervention period. Decolonization entailed the use of chlorhexidine for all routine bathing and showering and administration of nasal povidone-iodine twice daily for the first 5 days after admission and then twice daily for 5 days every other week. The primary outcome was transfer to a hospital due to infection. The secondary outcome was transfer to a hospital for any reason. An intention-to-treat (as-assigned) difference-in-differences analysis was performed for each outcome with the use of generalized linear mixed models to compare the intervention period with the baseline period across trial groups. RESULTS: Data were obtained from 28 nursing homes with a total of 28,956 residents. Among the transfers to a hospital in the routine-care group, 62.2% (the mean across facilities) were due to infection during the baseline period and 62.6% were due to infection during the intervention period (risk ratio, 1.00; 95% confidence interval [CI], 0.96 to 1.04). The corresponding values in the decolonization group were 62.9% and 52.2% (risk ratio, 0.83; 95% CI, 0.79 to 0.88), for a difference in risk ratio, as compared with routine care, of 16.6% (95% CI, 11.0 to 21.8; P<0.001). Among the discharges from the nursing home in the routine-care group, transfer to a hospital for any reason accounted for 36.6% during the baseline period and for 39.2% during the intervention period (risk ratio, 1.08; 95% CI, 1.04 to 1.12). The corresponding values in the decolonization group were 35.5% and 32.4% (risk ratio, 0.92; 95% CI, 0.88 to 0.96), for a difference in risk ratio, as compared with routine care, of 14.6% (95% CI, 9.7 to 19.2). The number needed to treat was 9.7 to prevent one infection-related hospitalization and 8.9 to prevent one hospitalization for any reason. CONCLUSIONS: In nursing homes, universal decolonization with chlorhexidine and nasal iodophor led to a significantly lower risk of transfer to a hospital due to infection than routine care. (Funded by the Agency for Healthcare Research and Quality; Protect ClinicalTrials.gov number, NCT03118232.). |
Minimal transmission in an influenza A (H3N2) human challenge-transmission model within a controlled exposure environment (preprint)
Nguyen-Van-Tam JS , Killingley B , Enstone J , Hewitt M , Pantelic J , Grantham ML , Bueno de Mesquita PJ , Lambkin-Williams R , Gilbert A , Mann A , Forni J , Noakes CJ , Levine MZ , Berman L , Lindstrom S , Cauchemez S , Bischoff W , Tellier R , Milton DK . medRxiv 2020 2019.12.13.19014381 Uncertainty about the importance of influenza transmission by airborne droplet nuclei generates controversy for infection control. Human challenge-transmission studies have been supported as the most promising approach to fill this knowledge gap. Healthy, seronegative volunteer ‘Donors’ (n=52) were randomly selected for intranasal challenge with influenza A/Wisconsin/67/2005 (H3N2). ‘Recipients’ randomized to Intervention (IR, n=40) or Control (CR, n=35) groups were exposed to Donors for four days. IRs wore face shields and hand sanitized frequently to limit large droplet and contact transmission. One transmitted infection was confirmed by serology in a CR, yielding a secondary attack rate of 2.9% among CR, 0% in IR (p=0.47 for group difference), and 1.3% overall, significantly less than 16% (p<0.001) expected based on a proof-of-concept study secondary attack rate and considering that there were twice as many Donors and days of exposure. The main difference between these studies was mechanical building ventilation in the follow-on study, suggesting a possible role for aerosols.Author summary Understanding the relative importance of influenza modes of transmission informs strategic use of preventive measures to reduce influenza risk in high-risk settings such as hospitals and is important for pandemic preparedness. Given the increasing evidence from epidemiological modelling, exhaled viral aerosol, and aerobiological survival studies supporting a role for airborne transmission and the potential benefit of respirators (and other precautions designed to prevent inhalation of aerosols) versus surgical masks (mainly effective for reducing exposure to large droplets) to protect healthcare workers, more studies are needed to evaluate the extent of risk posed airborne versus contact and large droplet spray transmission modes. New human challenge-transmission studies should be carefully designed to overcome limitations encountered in the current study. The low secondary attack rate reported herein also suggests that the current challenge-transmission model may no longer be a more promising approach to resolving questions about transmission modes than community-based studies employing environmental monitoring and newer, state-of-the-art deep sequencing-based molecular epidemiological methods.Competing Interest StatementJSN-V-T and BK declare previous consultancy fees from H-Vivo plc, unrelated to the current work. JSN-V-T is currently seconded to the Department of Health and Social Care (DHSC), England; the views expressed in this paper are not necessarily those of DHSC. RLW, AG and AM are employees of H-Vivo plc each of whom hold shares and /or share options in the company.Clinical TrialNCT01710111Funding StatementThis work was supported by U.S. CDC, Cooperative Agreement: Grant Number 1U01P000497-01. The views expressed in this paper are those of the authors and do not necessarily represent the official position of the funding agency.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData required for reproduction of analyses is available upon request. Scripts and other documentati n to reproduce analyses are available at Digital Repositories at the University of Maryland (13) and https://gitlab.com/jacobbueno/emit_quarantine_main. http://drum.lib.umd.edu/handle/1903/25315 |
Micronutrient powders and diarrhoea risk in infants and young children
Suchdev PS , Jefferds ME , Dewey KG , Zlotkin S , Aguayo VM , de Pee S , Kraemer K , Greig A , Arabi M , De-Regil LM . Lancet Child Adolesc Health 2021 5 (8) e28-e29 Emily Keats and colleagues 1 revisited the evidence base of maternal and child nutrition interventions using updated systematic reviews. The authors recommend micronutrient powders as an effective intervention to reduce childhood anaemia and iron deficiency, in line with WHO recommendations. 2 Using data from a 2020 systematic review by Tam and colleagues, 3 the authors reported a 30% increased risk of diarrhoea (relative risk [RR] 1·30 [95% CI 1·11–1·53) associated with micronutrient powders. This finding contrasts with findings from two Cochrane reviews of micronutrient powders that found no association between micronutrient powder use and diarrhoea in children aged 6–23 months (odds ratio [OR] 1·05 [95% CI 0·82–1·35]) and 2–12 years (RR 0·97 [95% CI 0·53–1·78]). 4 , 5 We raise several points to explain these differences. |
Biomarkers of Potential Harm among Adult Cigarette and Smokeless Tobacco Users in the PATH Study Wave 1 (2013-2014): A Cross-Sectional Analysis
Chang JT , Vivar JC , Tam J , Hammad HT , Christensen CH , van Bemmel DM , Das B , Danilenko U , Chang CM . Cancer Epidemiol Biomarkers Prev 2021 30 (7) 1320-1327 BACKGROUND: While smokeless tobacco (ST) is causes oral cancer and is associated with cardiovascular diseases, less is known about how its effects differ from other tobacco use. Biomarkers of potential harm (BOPH) can measure short-term health effects such as inflammation and oxidative stress. METHOD: We compared BOPH concentrations (interleukin-6 [IL-6], high-sensitivity C-reactive protein, fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1), and F2-isoprostane) across 3,460 adults in Wave 1 of the Population Assessment of Tobacco and Health Study (2013-2014) by tobacco use groups: primary ST users (current exclusive ST use among never smokers), secondary ST users (current exclusive ST use among former smokers), exclusive cigarette smokers, dual users of ST and cigarettes, former smokers, and never tobacco users. We estimated geometric mean ratios (GMRs) using never tobacco users, cigarette smokers, and former smokers as referents, adjusting for demographic and health conditions, creatinine (for F2-isoprostane), and pack-years in smoker referent models. RESULTS: BOPH levels among primary ST users were similar to both never tobacco users and former smokers. Most BOPH levels were lower among ST users compared to current smokers. Compared to never tobacco users, dual users had significantly higher sICAM-1, IL-6 and F2-isoprostane. However, compared to smokers, dual users had similar biomarker levels. Former smokers and secondary ST users had similar levels of all five biomarkers. CONCLUSIONS: ST users have lower levels of inflammatory and oxidative stress biomarkers than smokers. IMPACT: ST use alone and in combination with smoking may result in different levels of inflammatory and oxidative stress levels. |
A longitudinal comparison of alternatives to CDC BMI z-scores for children with very high BMIs
Freedman DS , Goodwin Davies AJ , Kompaniyets L , Lange SJ , Goodman AB , Tam Phan TL , Cole FS , Dempsey A , Pajor N , Eneli I , Christakis DA , Forrest CB . J Pediatr 2021 235 156-162 OBJECTIVE: The current CDC BMI z-scores are inaccurate for BMIs ≥ 97(th) percentile. We, therefore, considered 5 alternatives that can be used across the entire BMI distribution: modified BMIz, %CDC95th percentile, extended BMIz, %median, and %median adjusted for the dispersion of BMIs. STUDY DESIGN: We illustrate the behavior of the metrics among children of different ages and BMIs. We then compared the longitudinal tracking of the BMI metrics in electronic health record (EHR) data from 1.17 million children in PEDSnet using the intraclass correlation coefficient (ICC) to determine if one metric was superior. RESULTS: Our examples show that using CDC BMIz for high BMIs can result in nonsensical results. All alternative metrics showed higher tracking than CDC BMIz among children with obesity. Of the alternatives, modified BMIz performed poorly among children with severe obesity, and %median performed poorly among children who did not have obesity at their first visit. The highest ICCs were generally seen for extended BMIz, adjusted %median, and %CDC95(th) percentile. CONCLUSIONS: Based on the examples of differences in the BMI metrics, the longitudinal tracking results, and current familiarity BMI z-scores and percentiles, extended BMIz and extended BMI percentile may be suitable replacements for the current z-scores and percentiles. These metrics are identical to those in the CDC growth charts for BMIs < 95(th) percentile and are superior for very high BMIs. Researchers' familiarity with the current CDC z-scores and clinicians with the CDC percentiles may ease the transition to the extended BMI scale. |
Estimation of the critical external heat leading to the failure of lithium-ion batteries
Tang W , Tam WC , Yuan L , Dubaniewicz T , Thomas R , Soles J . Appl Therm Eng 2020 179 A detailed experimental investigation on the critical external heat leading to the failure of lithium-ion (Li-ion) batteries was conducted using an Accelerating Rate Calorimeter (ARC) at the National Institute for Occupational Safety and Health (NIOSH). Several types of commercial Li-ion batteries were selected for the study, including an iron phosphate Li-ion battery (LFP), a lithium-titanate battery (LTO), and a lithium-nickel-manganese-cobalt-oxide battery (NMC). Each battery was placed in a specially designed sealed steel canister and heated in the ARC. Battery voltage throughout the test was monitored and used to indicate the time to a battery failure. Three thermocouples, one attached to the battery surface, one measuring air temperature inside the canister, and one attached to the canister's internal surface, were used to record temperature changes during the heating tests. Different thermal behaviors were observed for the various battery types. An analytical model was developed to estimate the total external heat received by the battery using the measured temperatures. Experimental data ranked the batteries tested in terms of the heat to failure as: LFP 26,650 (11 kJ) > LFP 18650 (4.3 kJ) > NMC 18650 MH1 (3.6 kJ) ≈ LTO 18650 (3.6 kJ) > NMC 18650 HG2 (3 kJ). Total heat normalized to the battery nominal energy capacity was also calculated and ranked as: LTO 18650 ≈ LFP 26650 ≈ LFP 18650 > NMC 18650 MH1 ≈ NMC 18650 HG2. The test and analysis method developed can be extended to other types of batteries with a cylindrical shape. Results from this work provide insights to the thermal safety of Li-ion batteries and can help enhance battery thermal design and management. |
Minimal transmission in an influenza A (H3N2) human challenge-transmission model within a controlled exposure environment
Nguyen-Van-Tam JS , Killingley B , Enstone J , Hewitt M , Pantelic J , Grantham ML , Bueno de Mesquita PJ , Lambkin-Williams R , Gilbert A , Mann A , Forni J , Noakes CJ , Levine MZ , Berman L , Lindstrom S , Cauchemez S , Bischoff W , Tellier R , Milton DK . PLoS Pathog 2020 16 (7) e1008704 Uncertainty about the importance of influenza transmission by airborne droplet nuclei generates controversy for infection control. Human challenge-transmission studies have been supported as the most promising approach to fill this knowledge gap. Healthy, seronegative volunteer 'Donors' (n = 52) were randomly selected for intranasal challenge with influenza A/Wisconsin/67/2005 (H3N2). 'Recipients' randomized to Intervention (IR, n = 40) or Control (CR, n = 35) groups were exposed to Donors for four days. IRs wore face shields and hand sanitized frequently to limit large droplet and contact transmission. One transmitted infection was confirmed by serology in a CR, yielding a secondary attack rate of 2.9% among CR, 0% in IR (p = 0.47 for group difference), and 1.3% overall, significantly less than 16% (p<0.001) expected based on a proof-of-concept study secondary attack rate and considering that there were twice as many Donors and days of exposure. The main difference between these studies was mechanical building ventilation in the follow-on study, suggesting a possible role for aerosols. |
High prevalence of multidrug-resistant organism colonization in 28 nursing homes: An "iceberg effect"
McKinnell JA , Miller LG , Singh RD , Gussin G , Kleinman K , Mendez J , Laurner B , Catuna TD , Heim L , Saavedra R , Felix J , Torres C , Chang J , Estevez M , Mendez J , Tchakalian G , Bloomfield L , Ceja S , Franco R , Miner A , Hurtado A , Hean R , Varasteh A , Robinson PA , Park S , Tam S , Tjoa T , He J , Agrawal S , Yamaguchi S , Custodio H , Nguyen J , Bittencourt CE , Evans KD , Mor V , McConeghy K , Weinstein RA , Hayden MK , Stone ND , Steinberg K , Beecham N , Montgomery J , DeAnn W , Peterson EM , Huang SS . J Am Med Dir Assoc 2020 21 (12) 1937-1943 e2 OBJECTIVE: Determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum beta-lactamase producing organisms (ESBLs), and carbapenem-resistant Enterobacteriaceae (CRE) among residents and in the environment of nursing homes (NHs). DESIGN: Point prevalence sampling of residents and environmental sampling of high-touch objects in resident rooms and common areas. SETTING: Twenty-eight NHs in Southern California from 2016 to 2017. PARTICIPANTS: NH participants in Project PROTECT, a cluster-randomized trial of enhanced bathing and decolonization vs routine care. METHODS: Fifty residents were randomly sampled per NH. Twenty objects were sampled, including 5 common room objects plus 5 objects in each of 3 rooms (ambulatory, total care, and dementia care residents). RESULTS: A total of 2797 swabs were obtained from 1400 residents in 28 NHs. Median prevalence of multidrug-resistant organism (MDRO) carriage per NH was 50% (range: 24%-70%). Median prevalence of specific MDROs were as follows: MRSA, 36% (range: 20%-54%); ESBL, 16% (range: 2%-34%); VRE, 5% (range: 0%-30%); and CRE, 0% (range: 0%-8%). A median of 45% of residents (range: 24%-67%) harbored an MDRO without a known MDRO history. Environmental MDRO contamination was found in 74% of resident rooms and 93% of common areas. CONCLUSIONS AND IMPLICATIONS: In more than half of the NHs, more than 50% of residents were colonized with MDROs of clinical and public health significance, most commonly MRSA and ESBL. Additionally, the vast majority of resident rooms and common areas were MDRO contaminated. The unknown submerged portion of the iceberg of MDRO carriers in NHs may warrant changes to infection prevention and control practices, particularly high-fidelity adoption of universal strategies such as hand hygiene, environmental cleaning, and decolonization. |
Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria.
Raj DK , Das Mohapatra A , Jnawali A , Zuromski J , Jha A , Cham-Kpu G , Sherman B , Rudlaff RM , Nixon CE , Hilton N , Oleinikov AV , Chesnokov O , Merritt J , Pond-Tor S , Burns L , Jolly G , Ben Mamoun C , Kabyemela E , Muehlenbachs A , Lambert L , Orr-Gonzalez S , Gnadig NF , Fidock DA , Park S , Dvorin JD , Pardi N , Weissman D , Mui BL , Tam YK , Friedman JF , Fried M , Duffy PE , Kurtis JD . Nature 2020 582 (7810) 104-108 Malaria caused by Plasmodium falciparum remains the leading single-agent cause of mortality in children1, yet the promise of an effective vaccine has not been fulfilled. Here, using our previously described differential screening method to analyse the proteome of blood-stage P. falciparum parasites2, we identify P. falciparum glutamic-acid-rich protein (PfGARP) as a parasite antigen that is recognized by antibodies in the plasma of children who are relatively resistant—but not those who are susceptible—to malaria caused by P. falciparum. PfGARP is a parasite antigen of 80 kDa that is expressed on the exofacial surface of erythrocytes infected by early-to-late-trophozoite-stage parasites. We demonstrate that antibodies against PfGARP kill trophozoite-infected erythrocytes in culture by inducing programmed cell death in the parasites, and that vaccinating non-human primates with PfGARP partially protects against a challenge with P. falciparum. Furthermore, our longitudinal cohort studies showed that, compared to individuals who had naturally occurring anti-PfGARP antibodies, Tanzanian children without anti-PfGARP antibodies had a 2.5-fold-higher risk of severe malaria and Kenyan adolescents and adults without these antibodies had a twofold-higher parasite density. By killing trophozoite-infected erythrocytes, PfGARP could synergize with other vaccines that target parasite invasion of hepatocytes or the invasion of and egress from erythrocytes. |
Comparative immunogenicity of several enhanced influenza vaccine options for older adults: A randomized, controlled trial
Cowling BJ , Perera Rapm , Valkenburg SA , Leung NHL , Iuliano AD , Tam YH , Wong JHF , Fang VJ , Li APY , So HC , Ip DKM , Azziz-Baumgartner E , Fry AM , Levine MZ , Gangappa S , Sambhara S , Barr IG , Skowronski DM , Peiris JSM , Thompson MG . Clin Infect Dis 2019 71 (7) 1704-1714 BACKGROUND: Enhanced influenza vaccines may improve protection for older adults, but comparative immunogenicity data are limited. Our objective was to examine immune responses to enhanced influenza vaccines, compared to standard-dose vaccines, in community-dwelling older adults. METHODS: Community-dwelling older adults aged 65-82 years in Hong Kong were randomly allocated (October 2017-January 2018) to receive 2017-2018 Northern hemisphere formulations of a standard-dose quadrivalent vaccine, MF59-adjuvanted trivalent vaccine, high-dose trivalent vaccine, or recombinant-hemagglutinin (rHA) quadrivalent vaccine. Sera collected from 200 recipients of each vaccine before and at 30-days postvaccination were assessed for antibodies to egg-propagated vaccine strains by hemagglutination inhibition (HAI) and to cell-propagated A/Hong Kong/4801/2014(H3N2) virus by microneutralization (MN). Influenza-specific CD4+ and CD8+ T cell responses were assessed in 20 participants per group. RESULTS: Mean fold rises (MFR) in HAI titers to egg-propagated A(H1N1) and A(H3N2) and the MFR in MN to cell-propagated A(H3N2) were statistically significantly higher in the enhanced vaccine groups, compared to the standard-dose vaccine. The MFR in MN to cell-propagated A(H3N2) was highest among rHA recipients (4.7), followed by high-dose (3.4) and MF59-adjuvanted (2.9) recipients, compared to standard-dose recipients (2.3). Similarly, the ratio of postvaccination MN titers among rHA recipients to cell-propagated A(H3N2) recipients was 2.57-fold higher than the standard-dose vaccine, which was statistically higher than the high-dose (1.33-fold) and MF59-adjuvanted (1.43-fold) recipient ratios. Enhanced vaccines also resulted in the boosting of T-cell responses. CONCLUSIONS: In this head-to-head comparison, older adults receiving enhanced vaccines showed improved humoral and cell-mediated immune responses, compared to standard-dose vaccine recipients. CLINICAL TRIALS REGISTRATION: NCT03330132. |
Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection
Venkatesan S , Myles PR , Bolton KJ , Muthuri SG , Al Khuwaitir T , Anovadiya AP , Azziz-Baumgartner E , Bajjou T , Bassetti M , Beovic B , Bertisch B , Bonmarin I , Booy R , Borja-Aburto VH , Burgmann H , Cao B , Carratala J , Chinbayar T , Cilloniz C , Denholm JT , Dominguez SR , Duarte PAD , Dubnov-Raz G , Fanella S , Gao Z , Gerardin P , Giannella M , Gubbels S , Herberg J , Higuera Iglesias AL , Hoeger PH , Hu XY , Islam QT , Jimenez MF , Keijzers G , Khalili H , Kusznierz G , Kuzman I , Langenegger E , Lankarani KB , Leo YS , Libster RP , Linko R , Madanat F , Maltezos E , Mamun A , Manabe T , Metan G , Mickiene A , Mikic D , Mohn KGI , Oliva ME , Ozkan M , Parekh D , Paul M , Rath BA , Refaey S , Rodriguez AH , Sertogullarindan B , Skret-Magierlo J , Somer A , Talarek E , Tang JW , To K , Tran D , Uyeki TM , Vaudry W , Vidmar T , Zarogoulidis P , Nguyen-Van-Tam JS . J Infect Dis 2019 221 (3) 356-366 BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment. |
Association between HIV-1 subtype and drug resistance in Nigerian infants
Chaplin B , Akanmu AS , Inzaule SC , Samuels JO , Okonkwo P , Ilesanmi O , Adewole IFA , Asadu C , Khamofu H , Mpazanje R , Ndembi N , Odafe S , Sigaloff KCE , Ngige EN , Abatta EO , Akinbiyi G , Dakum P , Rinke de Wit TF , Kanki P . J Antimicrob Chemother 2019 74 (1) 172-176 Background: Many lines of evidence point to HIV-1 subtype-specific differences in the development of drug resistance mutations. While variation between subtype C and others has been extensively explored, there has been less emphasis on subtypes common to West Africa. We examined a previously described national survey of pretreatment drug resistance in HIV-1-infected Nigerian children aged <18 months, to explore the association between subtypes and patterns of resistance. Methods: Five hundred and forty-nine dried blood spots, from 15 early infant diagnostic facilities in Nigeria, were amplified and HIV-1 polymerase was sequenced. Four hundred and twenty-four were analysed for surveillance drug resistance mutations (SDRMs). Associations between subtype and SDRMs were evaluated by Fisher's exact test and logistic regression analysis, controlling for geographical region and exposure. Results: Using the sub-subtypes of HIV-1 G defined by Delatorre et al. (PLoS One 2014. 9: e98908) the most common subtypes were CRF02_AG (174, 41.0%), GWA-I (128, 30.2%), GWA-II (24, 5.7%), GCA (11, 2.6%), A (21, 5.0%) and CRF06_cpx (18, 4.2%). One hundred and ninety infants (44.8%) had >/=1 NNRTI mutation, 92 infants (21.7%) had >/=1 NRTI mutation and 6 infants (1.4%) had >/=1 PI mutation. By logistic regression, 67N was more common in GWA-II/GCA than CRF02_AG (OR 12.0, P = 0.006), as was 70R (OR 23.1, P = 0.007), 184I/V (OR 2.92, P = 0.020), the presence of >/=1 thymidine analogue mutation (TAM) (OR 3.87, P = 0.014), >/=1 type 2 TAM (OR 7.61, P = 0.001) and >/=1 NRTI mutation (OR 3.26, P = 0.005). Conclusions: This dataset reveals differences among SDRMs by subtype; in particular, between the GWA-II and GCA subclades, compared with CRF02_AG and GWA-I. |
The SHIELD Orange County Project - multi drug-resistant organism (MDRO) prevalence in 21 nursing homes and long term acute care facilities in southern California
McKinnell JA , Singh RD , Miller LG , Kleinman K , Gussin G , He J , Saavedra R , Dutciuc TD , Estevez M , Chang J , Heim L , Yamaguchi S , Custodio H , Gohil SK , Park S , Tam S , Robinson PA , Tjoa T , Nguyen J , Evans KD , Bittencourt CE , Lee BY , Mueller LE , Bartsch SM , Jernigan JA , Slayton RB , Stone ND , Zahn M , Mor V , McConeghy K , Baier RR , Janssen L , O'Donnell K , Weinstein RA , Hayden MK , Coady MH , Bhattarai M , Peterson EM , Huang SS . Clin Infect Dis 2019 69 (9) 1566-1573 Background: Multidrug-resistant organisms (MDROs) spread between hospitals, nursing homes (NH), and long-term acute care facilities (LTACs) via patient transfers. SHIELD OC is a regional public health collaborative involving decolonization at 38 healthcare facilities selected based upon their high degree of patient sharing. We report baseline MDRO prevalence in 21 NH/LTACs. Methods: A random sample of 50 adults for 21 NH/LTACs (18 NHs, 3 LTACs) were screened for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum beta-lactamase producing organisms (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE) using nares, skin (axilla/groin), and peri-rectal swabs. Facility and resident characteristics associated with MDRO carriage were assessed using multivariable models clustering by person and facility. Results: Prevalence of MDROs was 65% in NHs and 80% in LTACs. The most common MDROs in NHs were MRSA (42%) and ESBL (34%); in LTACs they were VRE (55%) and ESBL (38%). CRE prevalence was higher in facilities that manage ventilated LTAC patients and NH residents (8% vs. <1%, p<0.001). MDRO status was known for 18% of NH residents and 49% of LTAC patients. MDRO colonized adults commonly harbored additional MDROs (54% MDRO+ NH residents and 62% MDRO+ LTACs patients). History of MRSA [OR=1.7 C.I. (1.2, 2.4),p=0.004], VRE [OR=2.1 C.I.(1.2, 3.8),p=0.01], ESBL [OR=1.6 C.I.(1.1, 2.3),p=0.03] and diabetes [OR=1.3 C.I.(1.0, 1.7),p=0.03] were associated with any MDRO carriage. Conclusions: The majority of NH residents and LTACs patients harbor MDROs. MDRO status is frequently unknown to the facility. The high MDRO prevalence highlights the need for prevention efforts in NH/LTACs as part of regional efforts to control MDRO spread. |
Building a network for multicenter, prospective research of central nervous system infections in South America: Process and lessons learned
Nelson C , Mori N , Ton T , Zunt J , Kochel T , Romero A , Gadea N , Tilley D , Ticona E , Soria J , Celis V , Huanca D , Delgado A , Rivas M , Stiglich M , Sihuincha M , Donayre G , Celis J , Romero R , Tam N , Tipismana M , Espinoza I , Rozas M , Peralta A , Sanchez E , Vasquez L , Muñoz P , Ramirez G , Reyes Ifgt . eNeurologicalSci 2018 13 63-69 Multicenter collaborative networks are essential for advancing research and improving clinical care for a variety of conditions. Research networks are particularly important for central nervous system infections, which remain difficult to study due to their sporadic occurrence and requirement for collection and testing of cerebrospinal fluid. Establishment of long-term research networks in resource-limited areas also facilitates diagnostic capacity building, surveillance for emerging pathogens, and provision of appropriate treatment where needed. We review our experience developing a research network for encephalitis among twelve hospitals in five Peruvian cities since 2009. We provide practical suggestions to aid other groups interested in advancing research on central nervous system infections in resource-limited areas. |
Antiviral treatment for outpatient use during an influenza pandemic: a decision tree model of outcomes averted and cost-effectiveness
Venkatesan S , Carias C , Biggerstaff M , Campbell AP , Nguyen-Van-Tam JS , Kahn E , Myles PR , Meltzer MI . J Public Health (Oxf) 2018 41 (2) 379-390 Background: Many countries have acquired antiviral stockpiles for pandemic influenza mitigation and a significant part of the stockpile may be focussed towards community-based treatment. Methods: We developed a spreadsheet-based, decision tree model to assess outcomes averted and cost-effectiveness of antiviral treatment for outpatient use from the perspective of the healthcare payer in the UK. We defined five pandemic scenarios-one based on the 2009 A(H1N1) pandemic and four hypothetical scenarios varying in measures of transmissibility and severity. Results: Community-based antiviral treatment was estimated to avert 14-23% of hospitalizations in an overall population of 62.28 million. Higher proportions of averted outcomes were seen in patients with high-risk conditions, when compared to non-high-risk patients. We found that antiviral treatment was cost-saving across pandemic scenarios for high-risk population groups, and cost-saving for the overall population in higher severity influenza pandemics. Antiviral effectiveness had the greatest influence on both the number of hospitalizations averted and on cost-effectiveness. Conclusions: This analysis shows that across pandemic scenarios, antiviral treatment can be cost-saving for population groups at high risk of influenza-related complications. |
Susceptibility of paramyxoviruses and filoviruses to inhibition by 2'-monofluoro- and 2'-difluoro-4'-azidocytidine analogs
Lo MK , Jordan PC , Stevens S , Tam Y , Deval J , Nichol ST , Spiropoulou CF . Antiviral Res 2018 153 101-113 Ebolaviruses, marburgviruses, and henipaviruses are zoonotic pathogens belonging to the Filoviridae and Paramyxoviridae families. They exemplify viruses that continue to spill over into the human population, causing outbreaks characterized by high mortality and significant clinical sequelae in survivors of infection. There are currently no approved small molecule therapeutics for use in humans against these viruses. In this study, we evaluated the antiviral activity of the nucleoside analog 4'-azidocytidine (4'N3-C, R1479) and its 2'-monofluoro- and 2'-difluoro-modified analogs (2'F-4'N3-C and 2'diF-4'N3-C) against representative paramyxoviruses (Nipah virus, Hendra virus, measles virus, and human parainfluenza virus 3) and filoviruses (Ebola virus, Sudan virus, and Ravn virus). We observed enhanced antiviral activity against paramyxoviruses with both 2'diF-4'N3-C and 2'F-4'N3-C compared to R1479. On the other hand, while R1479 and 2'diF-4'N3-C inhibited filoviruses similarly to paramyxoviruses, we observed 10-fold lower filovirus inhibition by 2'F-4'N3-C. To our knowledge, this is the first study to compare the susceptibility of paramyxoviruses and filoviruses to R1479 and its 2'-fluoro-modified analogs. The activity of these compounds against negative-strand RNA viruses endorses the development of 4'-modified nucleoside analogs as broad-spectrum therapeutics against zoonotic viruses of public health importance. |
Characterisation of a rare, reassortant human G10P[14] rotavirus strain detected in Honduras.
Quaye O , Roy S , Rungsrisuriyachai K , Esona MD , Xu Z , Tam KI , Banegas DJC , Rey-Benito G , Bowen MD . Mem Inst Oswaldo Cruz 2018 113 (1) 9-16 BACKGROUND: Although first detected in animals, the rare rotavirus strain G10P[14] has been sporadically detected in humans in Slovenia, Thailand, United Kingdom and Australia among other countries. Earlier studies suggest that the strains found in humans resulted from interspecies transmission and reassortment between human and bovine rotavirus strains. OBJECTIVES: In this study, a G10P[14] rotavirus genotype detected in a human stool sample in Honduras during the 2010-2011 rotavirus season, from an unvaccinated 30-month old boy who reported at the hospital with severe diarrhea and vomiting, was characterised to determine the possible evolutionary origin of the rare strain. METHODS: For the sample detected as G10P[14], 10% suspension was prepared and used for RNA extraction and sequence independent amplification. The amplicons were sequenced by next-generation sequencing using the Illumina MiSeq 150 paired end method. The sequence reads were analysed using CLC Genomics Workbench 6.0 and phylogenetic trees were constructed using PhyML version 3.0. FINDINGS: The next generation sequencing and phylogenetic analyses of the 11-segmented genome of the G10P[14] strain allowed classification as G10-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3. Six of the genes (VP1, VP2, VP3, VP6, NSP2 and NSP4) were DS-1-like. NSP1 and NSP5 were AU-1-like and NSP3 was T6, which suggests that multiple reassortment events occurred in the evolution of the strain. The phylogenetic analyses and genetic distance calculations showed that the VP7, VP4, VP6, VP1, VP3, NSP1, NSP3 and NSP4 genes clustered predominantly with bovine strains. NSP2 and VP2 genes were most closely related to simian and human strains, respectively, and NSP5 was most closely related to a rhesus strain. MAIN CONCLUSIONS: The genetic characterisation of the G10P[14] strain from Honduras suggests that its genome resulted from multiple reassortment events which were possibly mediated through interspecies transmissions. |
Improving the selection and development of influenza vaccine viruses - Report of a WHO informal consultation on improving influenza vaccine virus selection, Hong Kong SAR, China, 18-20 November 2015.
Hampson A , Barr I , Cox N , Donis RO , Hirve S , Jernigan D , Katz J , McCauley J , Motta F , Odagiri T , Tami JS , Waddell A , Webby R , Ziegler T , Zhang W . Vaccine 2017 35 (8) 1104-1109 Since 2010 the WHO has held a series of informal consultations to explore ways of improving the currently highly complex and time-pressured influenza vaccine virus selection and development process. In November 2015 experts from around the world met to review the current status of efforts in this field. Discussion topics included strengthening influenza surveillance activities to increase the availability of candidate vaccine viruses and improve the extent, timeliness and quality of surveillance data. Consideration was also given to the development and potential application of newer laboratory assays to better characterize candidate vaccine viruses, the potential importance of antibodies directed against influenza virus neuraminidase, and the role of vaccine effectiveness studies. Advances in next generation sequencing and whole genome sequencing of influenza viruses were also discussed, along with associated developments in synthetic genomics technologies, evolutionary analysis and predictive mathematical modelling. Discussions were also held on the late emergence of an antigenic variant influenza A(H3N2) virus in mid-2014 that could not be incorporated in time into the 2014-15 northern hemisphere vaccine. There was broad recognition that given the current highly constrained influenza vaccine development and production timeline it would remain impossible to incorporate any variant virus which emerged significantly long after the relevant WHO biannual influenza vaccine composition meetings. Discussions were also held on the development of pandemic and broadly protective vaccines, and on associated regulatory and manufacturing requirements and constraints. With increasing awareness of the health and economic burdens caused by seasonal influenza, the ever-present threat posed by zoonotic influenza viruses, and the significant impact of the 2014-15 northern hemisphere seasonal influenza vaccine mismatch, this consultation provided a very timely opportunity to share developments and exchange views. In all areas, a renewed and strengthened emphasis was placed on developing concrete and measurable actions and identifying the key stakeholders responsible for their implementation. |
Occult HIV-1 drug resistance to thymidine analogues following failure of first-line tenofovir combined with a cytosine analogue and nevirapine or efavirenz in sub Saharan Africa: A retrospective multi-centre cohort study
Gregson J , Kaleebu P , Marconi VC , van Vuuren C , Ndembi N , Hamers RL , Kanki P , Hoffmann CJ , Lockman S , Pillay D , de Oliveira T , Clumeck N , Hunt G , Kerschberger B , Shafer RW , Yang C , Raizes E , Kantor R , Gupta RK . Lancet Infect Dis 2016 17 (3) 296-304 BACKGROUND: HIV-1 drug resistance to older thymidine analogue nucleoside reverse transcriptase inhibitor drugs has been identified in sub-Saharan Africa in patients with virological failure of first-line combination antiretroviral therapy (ART) containing the modern nucleoside reverse transcriptase inhibitor tenofovir. We aimed to investigate the prevalence and correlates of thymidine analogue mutations (TAM) in patients with virological failure of first-line tenofovir-containing ART. METHODS: We retrospectively analysed patients from 20 studies within the TenoRes collaboration who had locally defined viral failure on first-line therapy with tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI; nevirapine or efavirenz) in sub-Saharan Africa. Baseline visits in these studies occurred between 2005 and 2013. To assess between-study and within-study associations, we used meta-regression and meta-analyses to compare patients with and without TAMs for the presence of resistance to tenofovir, cytosine analogue, or NNRTIs. FINDINGS: Of 712 individuals with failure of first-line tenofovir-containing regimens, 115 (16%) had at least one TAM. In crude comparisons, patients with TAMs had lower CD4 counts at treatment initiation than did patients without TAMs (60.5 cells per muL [IQR 21.0-128.0] in patients with TAMS vs 95.0 cells per muL [37.0-177.0] in patients without TAMs; p=0.007) and were more likely to have tenofovir resistance (93 [81%] of 115 patients with TAMs vs 352 [59%] of 597 patients without TAMs; p<0.0001), NNRTI resistance (107 [93%] vs 462 [77%]; p<0.0001), and cytosine analogue resistance (100 [87%] vs 378 [63%]; p=0.0002). We detected associations between TAMs and drug resistance mutations both between and within studies; the correlation between the study-level proportion of patients with tenofovir resistance and TAMs was 0.64 (p<0.0001), and the odds ratio for tenofovir resistance comparing patients with and without TAMs was 1.29 (1.13-1.47; p<0.0001) INTERPRETATION: TAMs are common in patients who have failure of first-line tenofovir-containing regimens in sub-Saharan Africa, and are associated with multidrug resistant HIV-1. Effective viral load monitoring and point-of-care resistance tests could help to mitigate the emergence and spread of such strains. FUNDING: The Wellcome Trust. |
The unrecognized burden of typhoid fever
Obaro SK , Iroh Tam PY , Mintz ED . Expert Rev Vaccines 2016 16 (3) 249-260 INTRODUCTION: Typhoid fever (TF), caused by Salmonella enterica serovar Typhi, is the most common cause of enteric fever, responsible for an estimated 129,000 deaths and more than 11 million cases annually. Although several reviews have provided global and regional TF disease burden estimates, major gaps in our understanding of TF epidemiology remain. Areas covered: We provide an overview of the gaps in current estimates of TF disease burden and offer suggestions for addressing them, so that affected communities can receive the full potential of disease prevention offered by vaccination and water, sanitation, and hygiene interventions. Expert commentary: Current disease burden estimates for TF do not capture cases from certain host populations, nor those with atypical presentations of TF, which may lead to substantial underestimation of TF cases and deaths. These knowledge gaps pose major obstacles to the informed use of current and new generation typhoid vaccines. |
Effectiveness of monovalent and pentavalent rotavirus vaccines in Guatemala
Gastanaduy PA , Contreras-Roldan I , Bernart C , Lopez B , Benoit SR , Xuya M , Munoz F , Desai R , Quaye O , Tam KI , Evans-Bowen DK , Parashar UD , Manish Patel , McCracken JP . Clin Infect Dis 2016 62 S121-S126 Background. Concerns remain about lower effectiveness and waning immunity of rotavirus vaccines in resource-poor populations. We assessed vaccine effectiveness against rotavirus in Guatemala, where both the monovalent (RV1; 2-dose series) and pentavalent (RV5; 3-dose series) vaccines were introduced in 2010. Methods. A case-control evaluation was conducted in 4 hospitals from January 2012 to August 2013. Vaccine status was compared between case patients (children with laboratory-confirmed rotavirus diarrhea) and 2 sets of controls: nondiarrhea "hospital" controls (matched by birth date and site) and nonrotavirus "test-negative" diarrhea controls (adjusted for age, birth month/year, and site). Vaccine effectiveness ([1 - odds ratio of vaccination] x 100%) was computed using logistic regression models. Results. We evaluated 213 case patients, 657 hospital controls, and 334 test-negative controls. Effectiveness of 2-3 doses of a rotavirus vaccine against rotavirus requiring emergency department visit or hospitalization was 74% (95% confidence interval [CI], 58%-84%) with hospital controls, and 52% (95% CI, 26%-69%) with test-negative controls. Using hospital controls, no significant difference in effectiveness was observed between infants 6-11 months (74% [95% CI, 18%-92%]) and children >=12 months of age (71% [95% CI, 44%-85%]) (P=.85), nor between complete courses of RV1 (63% [95% CI, 23%-82%]) and RV5 (69% [95% CI, 29%-87%]) (P=.96). An uncommon G12P[8] strain, partially heterotypic to strains in both vaccines, was identified in 89% of cases. Conclusions. RV1 and RV5 were similarly effective against severe rotavirus diarrhea caused by a heterotypic strain in Guatemala. This supports broader implementation of rotavirus vaccination in low-income countries where >90% global deaths from rotavirus occur. |
One-step multiplex real-time RT-PCR assay for detecting and genotyping wild-type group A rotavirus strains and vaccine strains (Rotarix® and RotaTeq®) in stool samples.
Gautam R , Mijatovic-Rustempasic S , Esona MD , Tam KI , Quaye O , Bowen MD . PeerJ 2016 4 e1560 BACKGROUND: Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live-attenuated rotavirus vaccines, RotaTeq(R) and Rotarix(R), has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. METHODS: In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix(R) and RotaTeq(R)) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix(R) NSP2 and RotaTeq(R) VP6 qRT-PCRs for detection of Rotarix(R) and RotaTeq(R) vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. RESULTS: The VP7 qRT-PCRs exhibited 98.8-100% sensitivity, 99.7-100% specificity, 85-95% efficiency and a limit of detection of 4-60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81-92% efficiency and limit of detection of 150-600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98.8-100% sensitivity, 100% specificity, 86-89% efficiency and a limit of detection of 12-400 copies per singleplex reactions. The VP4 qRT-PCRs exhibited 82-90% efficiency and limit of detection of 120-4000 copies in multiplex reaction. DISCUSSION: The one-step multiplex qRT-PCR assay will facilitate high-throughput rotavirus genotype characterization for monitoring circulating rotavirus wild-type strains causing rotavirus infections, determining the frequency of Rotarix(R) and RotaTeq(R) vaccine strains and vaccine-derived reassortants associated with AGE, and help to identify novel rotavirus strains derived by reassortment between vaccine and wild-type strains. |
Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an IPD meta-analysis
Muthuri SG , Venkatesan S , Myles PR , Leonardi-Bee J , Lim WS , Mamun AA , Anovadiya AP , Araujo WN , Azziz-Baumgartner E , Baez C , Bantar C , Barhoush MM , Bassetti M , Beovic B , Bingisser R , Bonmarin I , Borja-Aburto VH , Cao B , Carratala J , Cuezzo MR , Denholm JT , Dominguez SR , Duarte PA , Dubnov-Raz G , Echavarria M , Fanella S , Fraser J , Gao Z , Gerardin P , Giannella M , Gubbels S , Herberg J , Iglesias AL , Hoeger PH , Hoffmann M , Hu X , Islam QT , Jimenez MF , Kandeel A , Keijzers G , Khalili H , Khandaker G , Knight M , Kusznierz G , Kuzman I , Kwan AM , Amine IL , Langenegger E , Lankarani KB , Leo YS , Linko R , Liu P , Madanat F , Manabe T , Mayo-Montero E , McGeer A , Memish ZA , Metan G , Mikic D , Mohn KG , Moradi A , Nymadawa P , Ozbay B , Ozkan M , Parekh D , Paul M , Poeppl W , Polack FP , Rath BA , Rodriguez AH , Siqueira MM , Skret-Magierlo J , Talarek E , Tang JW , Torres A , Torun SH , Tran D , Uyeki TM , van Zwol A , Vaudry W , Velyvyte D , Vidmar T , Zarogoulidis P , Nguyen-Van-Tam JS . Influenza Other Respir Viruses 2015 10 (3) 192-204 BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on Influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta-analysis of individual participant data (IPD) from 20,634 hospitalised patients with laboratory confirmed A(H1N1)pdm09 (n=20,021) or clinically diagnosed (n=613) 'pandemic influenza'. The primary outcome was radiologically confirmed influenza-related pneumonia (IRP). Odds ratios (OR) were estimated using generalized linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Among 20,634 included participants, 5,978 (29.0%) had IRP; conversely, 3,349 (16.2%) had confirmed absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0.83 (95%CI 0.64 - 1.06; p=0.136)]. Among the 5,978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR=0.72 (0.44-1.17; p=0.180)] or likelihood of requiring ventilatory support [adj. OR=1.17 (0.71-1.92; p=0.537)]; but early treatment versus later significantly reduced mortality [adj. OR=0.70 (0.55-0.88; p=0.003)] and likelihood of requiring ventilatory support [adj. OR=0.68 (0.54-0.85; p=0.001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support. |
Multiplexed one-step RT-PCR VP7 and VP4 genotyping assays for rotaviruses using updated primers.
Esona MD , Gautam R , Tam KI , Williams A , Mijatovic-Rustempasic S , Bowen MD . J Virol Methods 2015 223 96-104 The current two-step VP7 and VP4 genotyping RT-PCR assays for rotaviruses have been linked consistently to genotyping failure in an estimated 30% of RVA positive samples worldwide. We have developed a VP7 and VP4 multiplexed one-step genotyping assays using updated primers generated from contemporary VP7 and VP4 sequences. To determine assay specificity and sensitivity, 17 reference virus strains, 6 non-target gastroenteritis viruses and 725 clinical samples carrying the most common VP7 (G1, G2, G3, G4, G9, and G12) and VP4 (P[4], P[6], P[8], P[9] and P[10]) genotypes were tested in this study. All reference RVA strain targets yielded amplicons of the expected sizes and non-target genotypes and gastroenteritis viruses were not detected by either assay. Out of the 725 clinical samples tested, the VP7 and VP4 assays were able to assigned specific genotypes to 711 (98.1%) and 714 (98.5%), respectively. The remaining unassigned samples were re-tested for RVA antigen using EIA and qRT-PCR assays and all were found to be negative. The overall specificity, sensitivity and limit of detection of the VP7 assay were in the ranges of 99.0-100%, 94.0-100% and 8.6x101 - 8.6x102 copies of RNA/reaction, respectively. For the VP4 assay, the overall specificity, sensitivity and limit of detection assay were in the ranges of 100%, 94.0-100% and ≤ 1 - 8.6x102 copies of RNA/reaction, respectively. Here we report two highly robust, accurate, efficient, affordable and documentable gel-based genotyping systems which are capable of genotyping 97.8% of the six common VP7 and 98.3% of the five common VP4 genotypes of RVA strains which are responsible for approximately 88.2% of all RVA infections worldwide. |
Phylodynamics of Enterovirus A71-Associated Hand, Foot and Mouth Disease in Viet Nam.
Geoghegan JL , Van Tan L , Kuhnert D , Halpin RA , Lin X , Simenauer A , Akopov A , Das SR , Stockwell TB , Shrivastava S , Ngoc NM , Uyen LT , Tuyen NT , Thanh TT , Hang VT , Qui PT , Hung NT , Khanh TH , Thinh LQ , Nhan LN , Van HM , Viet DC , Tuan HM , Viet HL , Hien TT , Chau NV , Thwaites G , Grenfell BT , Stadler T , Wentworth DE , Holmes EC , Van Doorn HR . J Virol 2015 89 (17) 8871-9 Enterovirus A71 (EV-A71) is a major cause of hand, foot and mouth disease (HFMD) and is particularly prevalent in parts of Southeast Asia, affecting thousands of children and infants each year. Revealing the evolutionary and epidemiological dynamics of EV-A71 through time and space is central to understanding its outbreak potential. We generated the full genome sequences of 200 EV-A71 strains sampled from various locations in Viet Nam between 2011-2013, and used these sequence data to determine the evolutionary history and phylodynamics of EV-A71 in Viet Nam, providing estimates of the effective reproduction number (Re) of the infection through time. In addition, we described the phylogeography of EV-A71 throughout Southeast Asia, documenting patterns of viral gene flow. Accordingly, our analysis reveals that a rapid genogroup switch from C4 to B5 likely took place during 2012 in Viet Nam. We show that the Re of subgenogroup C4 decreased during the time-frame of sampling, while that of B5 increased and remained >1 at the end of 2013, corresponding to a rise in B5 prevalence. Our study reveals that the subgenogroup B5 virus that emerged into Viet Nam is closely related to variants that were responsible for large epidemics in Malaysia and Taiwan and therefore extends our knowledge regarding its associated endemic area. Subgenogroup B5 evidently has the potential to cause more widespread outbreaks across Southeast Asia. IMPORTANCE: EV-A71 is one of many viruses that cause HFMD, a common syndrome that largely affects infants and children. HFMD usually causes only mild illness with no long-term consequences. Occasionally, however, severe infection may arise, especially in very young children, causing neurological complications and even death. EV-A71 is highly contagious and is associated with the most severe HFMD cases, with large and frequent epidemics of the virus recorded worldwide. Although major advances have been made in the development of a potential EV-A71 vaccine, there is no current prevention and little is known about the patterns and dynamics of EV-A71 spread. In this study we utilize full-length genome sequence data obtained from HFMD patients in Viet Nam, a geographical region where the disease has been endemic since 2003, to characterize the phylodynamics of this important emerging virus. |
Evaluation of BBL Sensi-Discs and FTA cards as sampling devices for detection of rotavirus in stool samples
Tam KI , Esona MD , Williams A , Ndze VN , Boula A , Bowen MD . J Virol Methods 2015 222 41-6 Rotavirus is the most important cause of severe childhood gastroenteritis worldwide. Rotavirus vaccines are available and rotavirus surveillance is carried out to assess vaccination impact. In surveillance studies, stool samples are stored typically at 4 degrees C or frozen to maintain sample quality. Uninterrupted cold storage is a problem in developing countries because of power interruptions. Cold-chain transportation of samples from collection sites to testing laboratories is costly. In this study, we evaluated the use of BBL Sensi-Discs and FTA(R) cards for storage and transportation of samples for virus isolation, EIA, and RT-PCR testing. Infectious rotavirus was recovered after 30 days of storage on Sensi-Discs at room temperature. We were able to genotype 98-99% of samples stored on Sensi-Discs and FTA(R) cards at temperatures ranging from -80 degrees C to 37 degrees C up to 180 days. A field sampling test using samples prepared and shipped from Cameroon, showed that both matrices yielded 100% genotyping success compared with whole stool and Sensi-Discs demonstrated 95% concordance with whole stool in EIA testing. The utilization of BBL Sensi-Discs and FTA(R) cards for stool sample storage and shipment has the potential to have great impact on global public health by facilitating surveillance and epidemiological investigations of rotavirus strains worldwide at a reduced cost. |
Outbreak of Gastroenteritis in Adults Due to Rotavirus Genotype G12P[8].
Pacilli M , Cortese MM , Smith S , Siston A , Samala U , Bowen MD , Parada JP , Tam KI , Rungsrisuriyachai K , Roy S , Esona MD , Black SR . Clin Infect Dis 2015 61 (4) e20-5 BACKGROUND: Rotavirus infection in adults is poorly understood and few rotavirus outbreaks among U.S. adults have been reported in the literature. We describe an outbreak due to genotype G12P[8] rotavirus among medical students, faculty and guests who attended a formal dinner event in April 2013. METHODS: A web-based questionnaire was distributed to event attendees. to collect symptom and exposure data. A clinical case was defined as a person who developed diarrhea after attending the formal event. A laboratory-confirmed case was defined as a clinical case who attended the formal event with rotavirus detected in stool by enzyme immunoassay or reverse transcription-PCR assay. RESULTS: Among 334 formal dinner attendees, 136 (41%) completed a web-based questionnaire; 58 (43%) respondents reported illness. Symptom onset ranged from 1 to 8 days, with peak onset 3 days after the event. In addition to diarrhea, predominant symptoms included fever (91%), abdominal pain (84%) and vomiting (49%). The median duration of illness was 2.5 days. Thirteen (22%) of 58 cases sought medical attention; none were hospitalized. Analysis of food exposures among questionnaire respondents did not identify significant associations between any specific food or drink item and illness. Stool specimens were negative for bacterial pathogens by culture, negative for norovirus by RT-PCR; four specimens were positive for rotavirus by EIA or PCR. G12P[8]-R1-C1-M1-A1-N1-T1-E1-H1 was identified as the causative full-genome genotype. CONCLUSION: Rotavirus outbreaks can occur among adults, including young adults. Health professionals should consider rotavirus as a cause of acute gastroenteritis in adults. |
- Page last reviewed:Feb 1, 2024
- Page last updated:May 13, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure