Last data update: Sep 23, 2024. (Total: 47723 publications since 2009)
Records 1-14 (of 14 Records) |
Query Trace: Raz K [original query] |
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Characterizing the etiology of recurrent tuberculosis using whole genome sequencing-Alaska, USA, 2008-2020
Springer YP , Tompkins ML , Newell K , Jones M , Burns S , Chandler B , Cowan LS , Kammerer JS , Posey JE , Raz KM , Rothoff M , Silk BJ , Vergnetti YL , McLaughlin JB , Talarico S . J Infect Dis 2024 BACKGROUND: Understanding the etiology of recurrent tuberculosis (rTB) is important for effective TB control. Prior to the advent of whole genome sequencing (WGS), attributing rTB to relapse or reinfection using genetic information was complicated by the limited resolution of conventional genotyping methods. METHODS: We applied a systematic method of evaluating whole genome single nucleotide polymorphism (wgSNP) distances and results of phylogenetic analyses to characterize the etiology of rTB in American Indian and Alaska Native (AIAN) persons in Alaska during 2008-2020. We contextualized our findings through descriptive analyses of surveillance data and results of a literature search for investigations that characterized rTB etiology using WGS. RESULTS: The percentage of TB cases in AIAN persons in Alaska classified as recurrent episodes (11.8%) was three times the national percentage (3.9%). Of 38 recurrent episodes included in genetic analyses, we attributed 25 (65.8%) to reinfection based on wgSNP distances and phylogenetic analyses; this proportion was the highest among 16 published point estimates identified through the literature search. By comparison, we attributed 11 of 38 (28.9%) and 6 of 38 (15.8%) recurrent episodes to reinfection based on wgSNP distances alone and on conventional genotyping methods, respectively. CONCLUSIONS: WGS and attribution criteria involving genetic distances and patterns of relatedness can provide an effective means of elucidating rTB etiology. Our findings indicate that rTB occurs at high proportions among AIAN persons in Alaska and is frequently attributable to reinfection, reinforcing the importance of active surveillance and control measures to limit the spread of TB disease in Alaskan AIAN communities. |
Survey of invasive mosquito surveillance and control capacity in Southeastern USA reveals training and resource needs
Nguyen V , Weaver-Romero AL , Wang X , Tavares Y , Bauer A , McDowell RC , Dorsainvil C , Eason MD , Malcolm AN , Raz CD , Byrd BD , Riegel C , Clark M , Ber J , Harrison RL , Evans CL , Zohdy S , Allen B , Campbell LP , Killingsworth D , Grey EW , Riles MT , Lee Y , Giordano BV . J Am Mosq Control Assoc 2023 39 (2) 108-121 Several invasive mosquito species that are nuisances or of medical and veterinary importance have been introduced into the Southeastern region of the USA, posing a threat to other species and the local ecosystems and/or increasing the risk of pathogen transmission to people, livestock, and domestic pets. Prompt and effective monitoring and control of invasive species is essential to prevent them from spreading and causing harmful effects. However, the capacity for invasive mosquito species surveillance is highly variable among mosquito control programs in the Southeast, depending on a combination of factors such as regional geography and climate, access to resources, and the ability to interact with other programs. To facilitate the development of invasive mosquito surveillance in the region, we, the Mosquito BEACONS (Biodiversity Enhancement and Control of Non-native Species) working group, conducted a survey on the capacities of various public health agencies and pest control agencies engaged in mosquito surveillance and control in seven Southeastern states (Alabama, Florida, Georgia, Louisiana, Mississippi, North Carolina, and South Carolina). Ninety control programs completed the survey, representing an overall response rate of 25.8%. We report key findings from our survey, emphasizing the training and resource needs, and discuss their implications for future invasive mosquito surveillance and control capacity building. By increasing communication and collaboration opportunities (e.g., real-time sharing of collection records, coordinated multistate programs), the establishment of Mosquito BEACONS and the implementation of this survey can accelerate knowledge transfer and improve decision support capacity in response to or in preparation for invasive mosquito surveillance and can establish infrastructure that can be used to inform programs around the world. |
Molecular surveillance for large outbreaks of tuberculosis in the United States, 2014-2018.
Raz KM , Talarico S , Althomsons SP , Kammerer JS , Cowan LS , Haddad MB , McDaniel CJ , Wortham JM , France AM , Powell KM , Posey JE , Silk BJ . Tuberculosis (Edinb) 2022 136 102232 OBJECTIVE: This study describes characteristics of large tuberculosis (TB) outbreaks in the United States detected using novel molecular surveillance methods during 2014-2016 and followed for 2 years through 2018. METHODS: We developed 4 genotype-based detection algorithms to identify large TB outbreaks of ≥10 cases related by recent transmission during a 3-year period. We used whole-genome sequencing and epidemiologic data to assess evidence of recent transmission among cases. RESULTS: There were 24 large outbreaks involving 518 cases; patients were primarily U.S.-born (85.1%) racial/ethnic minorities (84.1%). Compared with all other TB patients, patients associated with large outbreaks were more likely to report substance use, homelessness, and having been diagnosed while incarcerated. Most large outbreaks primarily occurred within residences among families and nonfamilial social contacts. A source case with a prolonged infectious period and difficulties in eliciting contacts were commonly reported contributors to transmission. CONCLUSION: Large outbreak surveillance can inform targeted interventions to decrease outbreak-associated TB morbidity. |
Tuberculosis Outbreaks in State Prisons, United States, 2011-2019.
Stewart RJ , Raz KM , Burns SP , Kammerer JS , Haddad MB , Silk BJ , Wortham JM . Am J Public Health 2022 112 (8) 1170-1179 Objectives. To understand the frequency, magnitude, geography, and characteristics of tuberculosis outbreaks in US state prisons. Methods. Using data from the National Tuberculosis Surveillance System, we identified all cases of tuberculosis during 2011 to 2019 that were reported as occurring among individuals incarcerated in a state prison at the time of diagnosis. We used whole-genome sequencing to define 3 or more cases within 2 single nucleotide polymorphisms within 3 years as clustered; we classified clusters with 6 or more cases during a 3-year period as tuberculosis outbreaks. Results. During 2011 to 2019, 566 tuberculosis cases occurred in 41 state prison systems (a median of 3 cases per state). A total of 19 tuberculosis genotype clusters comprising 134 cases were identified in 6 state prison systems; these clusters included a subset of 5 outbreaks in 2 states. Two Alabama outbreaks during 2011 to 2017 totaled 20 cases; 3 Texas outbreaks during 2014 to 2019 totaled 51 cases. Conclusions. Only Alabama and Texas reported outbreaks during the 9-year period; only Texas state prisons had ongoing transmission in 2019. Effective interventions are needed to stop tuberculosis outbreaks in Texas state prisons. (Am J Public Health. 2022;112(8):1170-1179. https://doi.org/10.2105/AJPH.2022.306864). |
Mutation of Mycobacterium tuberculosis and Implications for Using Whole-Genome Sequencing for Investigating Recent Tuberculosis Transmission.
Nelson KN , Talarico S , Poonja S , McDaniel CJ , Cilnis M , Chang AH , Raz K , Noboa WS , Cowan L , Shaw T , Posey J , Silk BJ . Front Public Health 2021 9 790544 Tuberculosis (TB) control programs use whole-genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) for detecting and investigating TB case clusters. Existence of few genomic differences between Mtb isolates might indicate TB cases are the result of recent transmission. However, the variable and sometimes long duration of latent infection, combined with uncertainty in the Mtb mutation rate during latency, can complicate interpretation of WGS results. To estimate the association between infection duration and single nucleotide polymorphism (SNP) accumulation in the Mtb genome, we first analyzed pairwise SNP differences among TB cases from Los Angeles County, California, with strong epidemiologic links. We found that SNP distance alone was insufficient for concluding that cases are linked through recent transmission. Second, we describe a well-characterized cluster of TB cases in California to illustrate the role of genomic data in conclusions regarding recent transmission. Longer presumed latent periods were inconsistently associated with larger SNP differences. Our analyses suggest that WGS alone cannot be used to definitively determine that a case is attributable to recent transmission. Methods for integrating clinical, epidemiologic, and genomic data can guide conclusions regarding the likelihood of recent transmission, providing local public health practitioners with better tools for monitoring and investigating TB transmission. |
A Cluster-based Method to Quantify Individual Heterogeneity in Tuberculosis Transmission.
Smith JP , Gandhi NR , Silk BJ , Cohen T , Lopman B , Raz K , Winglee K , Kammerer S , Benkeser D , Kramer M , Hill AN . Epidemiology 2021 33 (2) 217-227 BACKGROUND: Recent evidence suggests transmission of Mycobacterium tuberculosis (Mtb) may be characterized by extreme individual heterogeneity in secondary cases (i.e., few cases account for the majority of transmission). Such heterogeneity implies outbreaks are rarer but more extensive and has profound implications in infectious disease control. However, discrete person-to-person transmission events in TB are often unobserved, precluding our ability to directly quantify individual heterogeneity in TB epidemiology. METHODS: We used a modified negative binomial branching process model to quantify the extent of individual heterogeneity using only observed transmission cluster size distribution data (i.e., the simple sum of all cases in a transmission chain) without knowledge of individual-level transmission events. The negative binomial parameter k quantifies the extent of individual heterogeneity (generally, k<1 indicates extensive heterogeneity, and as k→∞ transmission becomes more homogenous). We validated the robustness of the inference procedure considering common limitations affecting cluster-size data. Finally, we demonstrate the epidemiologic utility of this method by applying it to aggregate United States molecular surveillance data from the U.S. Centers for Disease Control and Prevention. RESULTS: The cluster-based method reliably inferred k using TB transmission cluster data despite a high degree of bias introduced into the model. We found that the TB transmission in the United States was characterized by a high propensity for extensive outbreaks (k=0.09; 95% confidence interval: 0.09, 0.10). CONCLUSION: The proposed method can accurately quantify critical parameters that govern TB transmission using simple, more easily obtainable cluster data to improve our understanding of TB epidemiology. |
Logically Inferred Tuberculosis Transmission (LITT): A Data Integration Algorithm to Rank Potential Source Cases.
Winglee K , McDaniel CJ , Linde L , Kammerer S , Cilnis M , Raz KM , Noboa W , Knorr J , Cowan L , Reynolds S , Posey J , Sullivan Meissner J , Poonja S , Shaw T , Talarico S , Silk BJ . Front Public Health 2021 9 667337 Understanding tuberculosis (TB) transmission chains can help public health staff target their resources to prevent further transmission, but currently there are few tools to automate this process. We have developed the Logically Inferred Tuberculosis Transmission (LITT) algorithm to systematize the integration and analysis of whole-genome sequencing, clinical, and epidemiological data. Based on the work typically performed by hand during a cluster investigation, LITT identifies and ranks potential source cases for each case in a TB cluster. We evaluated LITT using a diverse dataset of 534 cases in 56 clusters (size range: 2-69 cases), which were investigated locally in three different U.S. jurisdictions. Investigators and LITT agreed on the most likely source case for 145 (80%) of 181 cases. By reviewing discrepancies, we found that many of the remaining differences resulted from errors in the dataset used for the LITT algorithm. In addition, we developed a graphical user interface, user's manual, and training resources to improve LITT accessibility for frontline staff. While LITT cannot replace thorough field investigation, the algorithm can help investigators systematically analyze and interpret complex data over the course of a TB cluster investigation. Code available at: https://github.com/CDCgov/TB_molecular_epidemiology/tree/1.0; https://zenodo.org/badge/latestdoi/166261171. |
Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020.
Stokes EK , Zambrano LD , Anderson KN , Marder EP , Raz KM , El Burai Felix S , Tie Y , Fullerton KE . MMWR Morb Mortal Wkly Rep 2020 69 (24) 759-765 The coronavirus disease 2019 (COVID-19) pandemic resulted in 5,817,385 reported cases and 362,705 deaths worldwide through May, 30, 2020,(dagger) including 1,761,503 aggregated reported cases and 103,700 deaths in the United States.( section sign) Previous analyses during February-early April 2020 indicated that age >/=65 years and underlying health conditions were associated with a higher risk for severe outcomes, which were less common among children aged <18 years (1-3). This report describes demographic characteristics, underlying health conditions, symptoms, and outcomes among 1,320,488 laboratory-confirmed COVID-19 cases individually reported to CDC during January 22-May 30, 2020. Cumulative incidence, 403.6 cases per 100,000 persons,( paragraph sign) was similar among males (401.1) and females (406.0) and highest among persons aged >/=80 years (902.0). Among 599,636 (45%) cases with known information, 33% of persons were Hispanic or Latino of any race (Hispanic), 22% were non-Hispanic black (black), and 1.3% were non-Hispanic American Indian or Alaska Native (AI/AN). Among 287,320 (22%) cases with sufficient data on underlying health conditions, the most common were cardiovascular disease (32%), diabetes (30%), and chronic lung disease (18%). Overall, 184,673 (14%) patients were hospitalized, 29,837 (2%) were admitted to an intensive care unit (ICU), and 71,116 (5%) died. Hospitalizations were six times higher among patients with a reported underlying condition (45.4%) than those without reported underlying conditions (7.6%). Deaths were 12 times higher among patients with reported underlying conditions (19.5%) compared with those without reported underlying conditions (1.6%). The COVID-19 pandemic continues to be severe, particularly in certain population groups. These preliminary findings underscore the need to build on current efforts to collect and analyze case data, especially among those with underlying health conditions. These data are used to monitor trends in COVID-19 illness, identify and respond to localized incidence increase, and inform policies and practices designed to reduce transmission in the United States. |
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. |
Influence of county sampling on past estimates of latent tuberculosis infection prevalence
Haddad MB , Raz KM , Hill AN , Navin TR , Castro KG , Winston CA , Gandhi NR , Lash TL . Ann Am Thorac Soc 2019 16 (8) 1069-1071 The National Health and Nutrition Examination Survey (NHANES) has tested for Mycobacterium tuberculosis infection three times: in 1971–1972, 1999–2000, and 2011–2012. Based on tuberculin skin test results, the estimated national prevalence of latent tuberculosis infection (LTBI) among adults was 11–18% in 1971–1972 but has remained less than or equal to 6% in subsequent NHANES cycles (1–4). A single 2-year NHANES cycle is designed to produce accurate and stable estimates for conditions with at least 10% prevalence in the noninstitutionalized civilian U.S. population (5–7), suggesting that NHANES might no longer be as nationally representative for LTBI as it is for more common health conditions. Approximately 30 counties were selected for each 2-year cycle (5). We wished to examine whether persons in selected counties might have been systematically more or less likely to have a positive tuberculin skin test result than their counterparts in the approximately 3,100 counties that were not selected for NHANES participation. |
Simple estimates for local prevalence of latent tuberculosis infection, United States, 2011-2015
Haddad MB , Raz KM , Lash TL , Hill AN , Kammerer JS , Winston CA , Castro KG , Gandhi NR , Navin TR . Emerg Infect Dis 2018 24 (10) 1930-1933 We used tuberculosis genotyping results to derive estimates of prevalence of latent tuberculosis infection in the United States. We estimated <1% prevalence in 1,981 US counties, 1%-<3% in 785 counties, and >3% in 377 counties. This method for estimating prevalence could be applied in any jurisdiction with an established tuberculosis surveillance system. |
Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication.
Aghamohammadi A , Abolhassani H , Kutukculer N , Wassilak SG , Pallansch MA , Kluglein S , Quinn J , Sutter RW , Wang X , Sanal O , Latysheva T , Ikinciogullari A , Bernatowska E , Tuzankina IA , Costa-Carvalho BT , Franco JL , Somech R , Karakoc-Aydiner E , Singh S , Bezrodnik L , Espinosa-Rosales FJ , Shcherbina A , Lau YL , Nonoyama S , Modell F , Modell V , Ozen A , Berlin A , Chouikha A , Partida-Gaytán A , Kiykim A , Prakash C , Suri D , Ayvaz DC , Peláez D , da Silva EE , Deordieva E , Pérez-Sánchez EE , Ulusoy E , Dogu F , Seminario G , Cuzcanci H , Triki H , Shimizu H , Tezcan I , Ben-Mustapha I , Sun J , Mazzucchelli JTL , Orrego JC , Pac M , Bolkov M , Giraldo M , Belhaj-Hmida N , Mekki N , Kuzmenko N , Karaca NE , Rezaei N , Diop OM , Baris S , Chan SM , Shahmahmoodi S , Haskologlu S , Ying W , Wang Y , Barbouche MR , McKinlay MA . Front Immunol 2017 8 685 Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame. |
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. |
Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data
Muthuri SG , Venkatesan S , Myles PR , Leonardi-Bee J , Al Khuwaitir TS , Al Mamun A , Anovadiya AP , Azziz-Baumgartner E , Baez C , Bassetti M , Beovic B , Bertisch B , Bonmarin I , Booy R , Borja-Aburto VH , Burgmann H , Cao B , Carratala J , Denholm JT , Dominguez SR , Duarte PA , Dubnov-Raz G , Echavarria M , Fanella S , Gao Z , Gerardin P , Giannella M , Gubbels S , Herberg J , Iglesias AL , Hoger PH , Hu X , Islam QT , Jimenez MF , Kandeel A , Keijzers G , Khalili H , Knight M , Kudo K , Kusznierz G , Kuzman I , Kwan AM , Amine IL , Langenegger E , Lankarani KB , Leo YS , Linko R , Liu P , Madanat F , Mayo-Montero E , McGeer A , Memish Z , Metan G , Mickiene A , Mikic D , Mohn KG , Moradi A , Nymadawa P , Oliva ME , Ozkan M , Parekh D , Paul M , Polack FP , Rath BA , Rodriguez AH , Sarrouf EB , Seale AC , Sertogullarindan B , Siqueira MM , Skret-Magierlo J , Stephan F , Talarek E , Tang JW , To KK , Torres A , Torun SH , Tran D , Uyeki TM , Van Zwol A , Vaudry W , Vidmar T , Yokota RT , Zarogoulidis P , Nguyen-Van-Tam JS . Lancet Respir Med 2014 2 (5) 395-404 BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS: We included data for 29 234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0.81; 95% CI 0.70-0.93; p=0.0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0.48; 95% CI 0.41-0.56; p<0.0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0.50; 95% CI 0.37-0.67; p<0.0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1.23] [95% CI 1.18-1.28]; p<0.0001 for the increasing HR with each day's delay). INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING: F Hoffmann-La Roche. |
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