Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-30 (of 38 Records) |
Query Trace: Pang H[original query] |
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Complete genome sequences of nine double recombinant vaccine-derived novel oral poliovirus type 2 genomes from Nigeria 2023-2024
Castro CJ , Oderinde BS , Poston KD , Mawashi KY , Bullard K , Akinola M , Meade C , Liu H , Hu F , Bullows JE , Gonzalez Z , Pang H , Sarris S , Agha C , Dybdahl-Sissoko N , Perry DB , McDuffie L , Henderson E , Burns CC , Jorba J , Baba M . Microbiol Resour Announc 2024 e0088124 We report the complete genome sequences of nine double recombinant vaccine-derived novel oral poliovirus type 2 genomes from acute flaccid paralysis (AFP) cases (n = 3), AFP case contacts (n = 4), and environmental surveillance sampling (n = 2) in Nigeria. |
Household transmission dynamics of asymptomatic SARS-CoV-2-infected children: A multinational, controlled case-ascertained prospective study
Funk A , Florin TA , Kuppermann N , Finkelstein Y , Kazakoff A , Baldovsky M , Tancredi DJ , Breslin K , Bergmann KR , Gardiner M , Pruitt CM , Liu DR , Neuman MI , Wilkinson M , Ambroggio L , Pang XL , Cauchemez S , Malley R , Klassen TP , Lee BE , Payne DC , Mahmud SM , Freedman SB . Clin Infect Dis 2024 BACKGROUND: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described. METHODS: In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls. After 14 days' follow-up we assessed the clinical (ie, symptomatic) and combined (ie, test-positive, or symptomatic) secondary attack rates (SARs) among household contacts. Additionally, post-COVID-19 condition (PCC) was assessed in SARS-CoV-2-positive participating children after 90 days' follow-up. RESULTS: A total of 111 test-positive and 256 SARS-CoV-2 test-negative asymptomatic children were enrolled between January 2021 and April 2022. After 14 days, excluding households with co-primary cases, the clinical SAR among household contacts of SARS-CoV-2-positive and -negative index children was 10.6% (19/179; 95% CI: 6.5%-16.1%) and 2.0% (13/663; 95% CI: 1.0%-3.3%), respectively (relative risk = 5.4; 95% CI: 2.7-10.7). In households with a SARS-CoV-2-positive index child, age <5 years, being pre-symptomatic (ie, developed symptoms after test), and testing positive during Omicron and Delta circulation periods (vs earlier) were associated with increased clinical and combined SARs among household contacts. Among 77 asymptomatic SARS-CoV-2-infected children with 90-day follow-up, 6 (7.8%; 95% CI: 2.9%-16.2%) reported PCC. CONCLUSIONS: Asymptomatic SARS-CoV-2-infected children, especially those <5 years, are important contributors to household transmission, with 1 in 10 exposed household contacts developing symptomatic illness within 14 days. Asymptomatic SARS-CoV-2-infected children may develop PCC. |
SARS-CoV-2 susceptibility of cell lines and substrates commonly used in diagnosis and isolation of influenza and other viruses (preprint)
Wang L , Fan X , Bonenfant G , Cui D , Hossain J , Jiang N , Larson G , Currier M , Liddell J , Wilson M , Tamin A , Harcourt J , Ciomperlik-Patton J , Pang H , Dybdahl-Sissoko N , Campagnoli R , Shi PY , Barnes J , Thornburg NJ , Wentworth DE , Zhou B . bioRxiv 2021 2021.01.04.425336 Coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses is inevitable as the COVID-19 pandemic continues. This study aimed to evaluate cell lines commonly used in virus diagnosis and isolation for their susceptibility to SARS-CoV-2. While multiple kidney cell lines from monkeys were susceptible and permissive to SARS-CoV-2, many cell types derived from human, dog, mink, cat, mouse, or chicken were not. Analysis of MDCK cells, which are most commonly used for surveillance and study of influenza viruses, demonstrated that they were insusceptible to SARS-CoV-2 and that the cellular barrier to productive infection was due to low expression level of the angiotensin converting enzyme 2 (ACE2) receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by over-expression of canine ACE2 in trans. Moreover, SARS-CoV-2 cell tropism did not appear to be affected by a D614G mutation in the spike protein.Competing Interest StatementThe authors have declared no competing interest. |
Mild and asymptomatic influenza B virus infection among unvaccinated pregnant persons: Implication for effectiveness of non-pharmaceutical intervention and vaccination to prevent influenza
Chen L , Levine MZ , Zhou S , Bai T , Pang Y , Bao L , Tan Y , Cui P , Zhang R , Millman AJ , Greene CM , Zhang Z , Wang Y , Zhang J . Vaccine 2023 41 (3) 694-701 BACKGROUND: We estimated symptomatic and asymptomatic influenza infection frequency in community-dwelling unvaccinated pregnant persons to inform risk communication. METHODS: We collected residue sera from multiple antenatal-care blood draws during October 2016-April 2017. We determined influenza infection as seroconversion with ≥ 4-fold rise in antibody titers between any two serum samples by improved hemagglutinin-inhibition assay including ether-treated B antigens. The serology data were linked to the results of nuclei acid testing (rRT-PCR) based on acute respiratory illness (ARI) surveillance. RESULTS: Among all participants, 43 %(602/1384) demonstrated serology and/or rRT-PCR evidenced infection, and 44 %(265/602) of all infections were asymptomatic. ARI-associated rRT-PCR testing identified only 10 %(61/602) of total infections. Only 1 %(5/420) of the B Victoria cases reported ARI and had a rRT-PCR positive result, compared with 33 %(54/165) of the H3N2 cases. Among influenza ARI cases with multiple serum samples, 19 %(11/58) had seroconversion to a different subtype prior to the illness. CONCLUSIONS: The incidence of influenza B infection in unvaccinated pregnant persons is under-estimated substantially. Non-pharmaceutical intervention may have suboptimal effectiveness in preventing influenza B transmission due to the less clinical manifestation compared to influenza A. The findings support maternal influenza vaccination to protect pregnant persons and reduce consequent household transmission. |
Influence of COVID-19 for delaying the diagnosis and treatment of pulmonary tuberculosis-Tianjin, China.
Zhang G , Yu Y , Zhang W , Shang J , Chen S , Pang X , Oeltmann JE , Moonan PK , Chen M , Zhang F . Front Public Health 2022 10 937844 BACKGROUND: The COVID-19 pandemic has disrupted the diagnosis, treatment, and care for tuberculosis (TB). Delays in seeking TB care may result in increased community transmission and unfavorable treatment outcomes. We sought to understand the influence of the COVID-19 pandemic on the proportion of patients with TB who delayed seeking the diagnosis and care for TB and explore the reasons for their postponement. METHODS: We surveyed a representative sample of outpatients treated for pulmonary TB from June to November 2020 using an anonymous standardized questionnaire. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) of factors associated with the postponement of TB care. We used routinely collected surveillance data to assess trends of TB reports before and after the emergence of COVID-19 (2017-2019 vs. 2020-2022) in Tianjin, China. RESULTS: Among 358 participants who were diagnosed with pulmonary TB during the COVID-19 response, 61 (17%) postponed seeking TB diagnosis due to COVID-19, with 39 (64%) citing fear as the primary reason. Female sex (aOR:2.0; 95% CI: 1.1-3.7), previous antituberculosis treatment (aOR:3.2; 95%CI: 1.4-7.6), and TB diagnosis during the first-level response (aOR = 3.2, 1.7-6.2) were associated with the postponement. Among all 518 participants receiving antituberculosis treatment, 57 (11%) had postponed their regular healthcare visits due to COVID-19, 175 (34%) received no treatment supervision, and 32 (6%) experienced treatment interruption. Compared to 2017-2019, reported pulmonary TB declined by 36.8% during the first-level response to COVID-19, 23.5% during the second-level response, 14% during the third-level response in 2020, and 4.3% in 2021. CONCLUSION: The COVID-19 response reduced the number of people who sought and received diagnosis, treatment, and care for TB in Tianjin, China. Integrative programs to ensure access and continuity of TB services should be considered and dual testing for SARS-CoV-2 and M. tuberculosis may facilitate finding cases. |
Nearly Complete Genome Sequences of Type 2 Sabin-Like Polioviruses from Northern Nigerian Poliovirus Surveillance, 2016 to 2018.
Zhao K , Schmidt A , Tang K , Castro CJ , Liu H , Pang H , Chen Q , Baba M , Soji OB , Bukbuk D , Akinola M , Adeniji JA , Marine RL , Ng TFF , Jorba J , Burns CC . Microbiol Resour Announc 2022 12 (1) e0073522 We sequenced 109 type 2 Sabin-like poliovirus isolates that had been collected from acute flaccid paralysis patients or healthy children in Nigeria. Understanding the genetic makeup of these viruses may contribute to polio eradication efforts. |
Discovery of substituted benzyloxy-benzylamine inhibitors of acetyltransferase Eis and their anti-mycobacterial activity
Pang AH , Green KD , Chandrika NT , Garzan A , Punetha A , Holbrook SYL , Willby MJ , Posey JE , Tsodikov OV , Garneau-Tsodikova S . Eur J Med Chem 2022 242 114698 A clinically significant mechanism of tuberculosis resistance to the aminoglycoside kanamycin (KAN) is its acetylation catalyzed by upregulated Mycobacterium tuberculosis (Mtb) acetyltransferase Eis. In search for inhibitors of Eis, we discovered an inhibitor with a substituted benzyloxy-benzylamine scaffold. A structure-activity relationship study of 38 compounds in this structural family yielded highly potent (IC(50) 1M) Eis inhibitors, which did not inhibit other acetyltransferases. Crystal structures of Eis in complexes with three of the inhibitors showed that the inhibitors were bound in the aminoglycoside binding site of Eis, consistent with the competitive mode of inhibition, as established by kinetics measurements. When tested in Mtb cultures, two inhibitors (47 and 55) completely abolished resistance to KAN of the highly KAN-resistant strain Mtb mc(2) 6230 K204, likely due to Eis inhibition as a major mechanism. Thirteen of the compounds were toxic even in the absence of KAN to Mtb and other mycobacteria, but not to non-mycobacteria or to mammalian cells. This, yet unidentified mechanism of toxicity, distinct from Eis inhibition, will merit future studies along with further development of these molecules as anti-mycobacterial agents. |
Structure-based design of haloperidol analogues as inhibitors of acetyltransferase Eis from Mycobacterium tuberculosis to overcome kanamycin resistance
Punetha A , Green KD , Garzan A , Thamban Chandrika N , Willby MJ , Pang AH , Hou C , Holbrook SYL , Krieger K , Posey JE , Parish T , Tsodikov OV , Garneau-Tsodikova S . RSC Med Chem 2021 12 (11) 1894-1909 Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a deadly bacterial disease. Drug-resistant strains of Mtb make eradication of TB a daunting task. Overexpression of the enhanced intracellular survival (Eis) protein by Mtb confers resistance to the second-line antibiotic kanamycin (KAN). Eis is an acetyltransferase that acetylates KAN, inactivating its antimicrobial function. Development of Eis inhibitors as KAN adjuvant therapeutics is an attractive path to forestall and overcome KAN resistance. We discovered that an antipsychotic drug, haloperidol (HPD, 1), was a potent Eis inhibitor with IC(50) = 0.39 ± 0.08 μM. We determined the crystal structure of the Eis-haloperidol (1) complex, which guided synthesis of 34 analogues. The structure-activity relationship study showed that in addition to haloperidol (1), eight analogues, some of which were smaller than 1, potently inhibited Eis (IC(50) ≤ 1 μM). Crystal structures of Eis in complexes with three potent analogues and droperidol (DPD), an antiemetic and antipsychotic, were determined. Three compounds partially restored KAN sensitivity of a KAN-resistant Mtb strain K204 overexpressing Eis. The Eis inhibitors generally did not exhibit cytotoxicity against mammalian cells. All tested compounds were modestly metabolically stable in human liver microsomes, exhibiting 30-60% metabolism over the course of the assay. While direct repurposing of haloperidol as an anti-TB agent is unlikely due to its neurotoxicity, this study reveals potential approaches to modifying this chemical scaffold to minimize toxicity and improve metabolic stability, while preserving potent Eis inhibition. |
Culture-Independent Detection of Poliovirus in Stool Samples by Direct RNA Extraction.
Harrington C , Sun H , Jeffries-Miles S , Gerloff N , Mandelbaum M , Pang H , Collins N , Burns CC , Vega E . Microbiol Spectr 2021 9 (3) e0066821 Laboratory surveillance for poliovirus (PV) relies on virus isolation by cell culture to identify PV in stool specimens from acute flaccid paralysis (AFP) cases. Although this method successfully identifies PV, it is time-consuming and necessitates the additional biorisk of growing live virus in an increasingly polio-free world. To reduce the risk of culturing PV, the Global Polio Laboratory Network (GPLN) must switch to culture-independent diagnostic methods with sensitivity at least equivalent to that of cell culture procedures. Five commercial nucleic acid extraction kits and one enrichment method were tested for PV extraction efficiency. RNA yield was measured using real-time reverse transcription (RT)-PCR. Based on greater RNA yield, compared with the other kits, the Quick-RNA viral kit was selected for further testing and was optimized using an RNA extraction procedure for stool suspensions. RNA extraction was retrospectively tested with 182 stool samples that had previously tested positive for PVs, in parallel with the standard GPLN virus isolation algorithm. After virus isolation or RNA extraction, real-time RT-PCR assays were performed. RNA extraction was significantly more sensitive than virus isolation (McNemar's test, P < 0.001). Thereafter, the RNA extraction method was tested in parallel for 202 prospective samples; RNA extraction and virus isolation were not significantly different from each other (McNemar's test, P = 0.13). Direct RNA extraction was noninferior to current cell culture methods for detecting PV in stool samples. Our results show that direct RNA extraction can make downstream manipulation safer and can reduce the risk of accidental posteradication viral release. The method is amenable to implementation in a wide variety of polio laboratories. IMPORTANCE Successfully identifying poliovirus from acute flaccid paralysis (AFP) cases is a vital role of the Global Polio Laboratory Network to achieve the goals of the Global Polio Eradication Initiative. Currently, laboratory surveillance relies on virus isolation by cell culture to test for PV present in stool samples. Although this method can identify polioviruses, laboratories must switch to culture-independent methods to reduce the risk associated with growing live viruses in a soon-to-be polio-free world. By implementing this streamlined method, in combination with real-time RT-PCR, laboratories can quickly screen for and type polioviruses of programmatic importance to support the final stages of global polio eradication. |
Direct detection of polioviruses using a recombinant poliovirus receptor.
Gerloff N , Mandelbaum M , Pang H , Collins N , Brown B , Sun H , Harrington C , Hecker J , Agha C , Burns CC , Vega E . PLoS One 2021 16 (11) e0259099 Polioviruses are positive-sense, single-stranded RNA picornaviruses and the principal cause of poliomyelitis. Global poliovirus surveillance has relied on poliovirus isolation in cells, which may take a minimum of 10 days, involves maintaining two cell lines, and propagates virus in high titers. With eradication underway, a major objective of the Global Polio Eradication Initiative (GPEI) is to develop culture-independent detection of polioviruses as an alternative method to complement the current virus isolation technique. A culture-independent method on poliovirus-positive stool suspensions was assessed with commercially available recombinant soluble poliovirus receptor (PVR) coupled to Histidine (His) tags. Viral RNA was screened by quantitative real-time reverse transcription PCR using the poliovirus intratypic differentiation kit. Poliovirus recovery was optimized with PVR-His-tagged protein and buffers supplemented with polyethylene glycol. To validate the poliovirus-PVR-His tag purification assay, 182 poliovirus-positive stools of programmatic importance were parallel tested against the GPLN-accepted virus isolation method. The PVR-His tag enrichment method detected poliovirus in 164 of 171 poliovirus-positive stools, whereas the virus isolation method misidentified 38 stools as poliovirus-negative (McNemar χ2 p<0.0001). Using this method in combination with RNA extraction, viral RNA recovery increased and showed similar (WPV1) or higher (Sabin 1) sensitivity than the World Health Organization accredited variation of the virus isolation method. The PVR-His enrichment method could be a viable addition to poliovirus surveillance; similar methods have the potential to capture other human pathogens such as EV71 using an appropriate soluble His tag receptor. |
Detection and Clinical Implications of Monovalent Rotavirus Vaccine-Derived Virus Strains in Children with Gastroenteritis in Alberta, Canada.
Zhuo R , Tarr G , Xie J , Freedman SB , Payne DC , Lee BE , McWilliams C , Chui L , Ali S , Pang X . J Clin Microbiol 2021 59 (11) Jcm0115421 Background: While rotavirus vaccine programs effectively protect against severe rotavirus gastroenteritis, rotavirus vaccine strains have been identified in the stool of vaccinated children and their close contacts suffering from acute gastroenteritis. The prevalence of vaccine strains, the emergence of vaccine-derived strains and their role in acute gastroenteritis are not well studied. Methods: We developed a Locked Nucleic Acid Reverse Transcription real-time PCR assay (LNA-RTqPCR) to detect the monovalent rotavirus vaccine (RV1) Rotarix non-structural protein 2 in children with acute gastroenteritis and healthy controls and validated it using sequence confirmed RV1 strains. The association between RV1-derived strains and gastroenteritis was determined using logistic regression. Results: The new assay exhibited 100% (95%CI: 91.7%, 100%) diagnostic sensitivity and 99.4% (95%CI: 96.2%, 100%) diagnostic specificity, with a detection limit of 9.86 copies/reaction and qPCR efficiency of 99.7%. Using this assay, we identified the presence of RV1-derived NSP2 sequences in 7.7% of rotavirus gastroenteritis cases and 98.6% of rotavirus positive healthy children (94.4% had previously received the RV1). Among gastroenteritis cases, those whose stool contained RV1-derived strains had milder gastroenteritis symptoms compared to that of natural rotavirus infections. We observed no significant association between RV1-derived strains and gastroenteritis (OR 0.98; 95% CI 0.60, 1.72). Conclusion: Our study demonstrated that the new assay is suitable for monitoring RV1-derived rotavirus strain circulation and that the RV1-derived strains are not associated with development of gastroenteritis symptoms. |
Incidence rates of influenza illness during pregnancy in Suzhou, China, 2015-2018
Chen L , Zhou S , Bao L , Millman AJ , Zhang Z , Wang Y , Tan Y , Song Y , Cui P , Pang Y , Liu C , Qin J , Zhang P , Thompson MG , Iuliano AD , Zhang R , Greene CM , Zhang J . Influenza Other Respir Viruses 2021 16 (1) 14-23 BACKGROUND: Data on influenza incidence during pregnancy in China are limited. METHODS: From October 2015 to September 2018, we conducted active surveillance for acute respiratory illness (ARI) among women during pregnancy. Nurses conducted twice weekly phone and text message follow-up upon enrollment until delivery to identify new episodes of ARI. Nasal and throat swabs were collected ≤10 days from illness onset to detect influenza. RESULTS: In total, we enrolled 18 724 pregnant women median aged 28 years old, 37% in first trimester, 48% in second trimester, and 15% in third trimester, with seven self-reported influenza vaccination during pregnancy. In the 18-week epidemic period during October 2015 to September 2016, influenza incidence was 0.7/100 person-months (95% CI: 0.5-0.9). In the cumulative 29-week-long epidemic during October 2016 to September 2017, influenza incidence was 1.0/100 person-months (95% CI: 0.8-1.2). In the 11-week epidemic period during October 2017 to September 2018, influenza incidence was 2.1/100 person-months (95% CI: 1.9-2.4). Influenza incidence was similar by trimester. More than half of the total influenza illnesses had no elevated temperature and cough. Most influenza-associated ARIs were mild, and <5.1% required hospitalization. CONCLUSIONS: Influenza illness in all trimesters of pregnancy was common. These data may help inform decisions regarding the use of influenza vaccine to prevent influenza during pregnancy. |
Global Trends in Norovirus Genotype Distribution among Children with Acute Gastroenteritis.
Cannon JL , Bonifacio J , Bucardo F , Buesa J , Bruggink L , Chan MC , Fumian TM , Giri S , Gonzalez MD , Hewitt J , Lin JH , Mans J , Muñoz C , Pan CY , Pang XL , Pietsch C , Rahman M , Sakon N , Selvarangan R , Browne H , Barclay L , Vinjé J . Emerg Infect Dis 2021 27 (5) 1438-1445 Noroviruses are a leading cause of acute gastroenteritis (AGE) among adults and children worldwide. NoroSurv is a global network for norovirus strain surveillance among children <5 years of age with AGE. Participants in 16 countries across 6 continents used standardized protocols for dual typing (genotype and polymerase type) and uploaded 1,325 dual-typed sequences to the NoroSurv web portal during 2016-2020. More than 50% of submitted sequences were GII.4 Sydney[P16] or GII.4 Sydney[P31] strains. Other common strains included GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses. In total, 22 genotypes and 36 dual types, including GII.3 and GII.20 viruses with rarely reported polymerase types, were detected, reflecting high strain diversity. Surveillance data captured in NoroSurv enables the monitoring of trends in norovirus strains associated childhood AGE throughout the world on a near real-time basis. |
Susceptibility to SARS-CoV-2 of Cell Lines and Substrates Commonly Used to Diagnose and Isolate Influenza and Other Viruses.
Wang L , Fan X , Bonenfant G , Cui D , Hossain J , Jiang N , Larson G , Currier M , Liddell J , Wilson M , Tamin A , Harcourt J , Ciomperlik-Patton J , Pang H , Dybdahl-Sissoko N , Campagnoli R , Shi PY , Barnes J , Thornburg NJ , Wentworth DE , Zhou B . Emerg Infect Dis 2021 27 (5) 1380-1392 Co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses has been reported. We evaluated cell lines commonly used to isolate viruses and diagnose related diseases for their susceptibility to SARS-CoV-2. Although multiple kidney cell lines from monkeys were susceptible to SARS-CoV-2, we found many cell types derived from humans, dogs, minks, cats, mice, and chicken were not. We analyzed MDCK cells, which are most commonly used for surveillance and study of influenza viruses, and found that they were not susceptible to SARS-CoV-2. The low expression level of the angiotensin converting enzyme 2 receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by overexpression of canine angiotensin converting enzyme 2 in trans, strengthened the cellular barrier to productive infection. Moreover, a D614G mutation in the spike protein did not appear to affect SARS-CoV-2 cell tropism. Our findings should help avert inadvertent propagation of SARS-CoV-2 from diagnostic cell lines. |
Trends in the incidence of diagnosed diabetes: a multicountry analysis of aggregate data from 22 million diagnoses in high-income and middle-income settings
Magliano DJ , Chen L , Islam RM , Carstensen B , Gregg EW , Pavkov ME , Andes LJ , Balicer R , Baviera M , Boersma-van Dam E , Booth GL , Chan JCN , Chua YX , Fosse-Edorh S , Fuentes S , Gulseth HL , Gurevicius R , Ha KH , Hird TR , Jermendy G , Khalangot MD , Kim DJ , Kiss Z , Kravchenko VI , Leventer-Roberts M , Lin CY , Luk AOY , Mata-Cases M , Mauricio D , Nichols GA , Nielen MM , Pang D , Paul SK , Pelletier C , Pildava S , Porath A , Read SH , Roncaglioni MC , Lopez-Doriga Ruiz P , Shestakova M , Vikulova O , Wang KL , Wild SH , Yekutiel N , Shaw JE . Lancet Diabetes Endocrinol 2021 9 (4) 203-211 BACKGROUND: Diabetes prevalence is increasing in most places in the world, but prevalence is affected by both risk of developing diabetes and survival of those with diabetes. Diabetes incidence is a better metric to understand the trends in population risk of diabetes. Using a multicountry analysis, we aimed to ascertain whether the incidence of clinically diagnosed diabetes has changed over time. METHODS: In this multicountry data analysis, we assembled aggregated data describing trends in diagnosed total or type 2 diabetes incidence from 24 population-based data sources in 21 countries or jurisdictions. Data were from administrative sources, health insurance records, registries, and a health survey. We modelled incidence rates with Poisson regression, using age and calendar time (1995-2018) as variables, describing the effects with restricted cubic splines with six knots for age and calendar time. FINDINGS: Our data included about 22 million diabetes diagnoses from 5 billion person-years of follow-up. Data were from 19 high-income and two middle-income countries or jurisdictions. 23 data sources had data from 2010 onwards, among which 19 had a downward or stable trend, with an annual estimated change in incidence ranging from -1·1% to -10·8%. Among the four data sources with an increasing trend from 2010 onwards, the annual estimated change ranged from 0·9% to 5·6%. The findings were robust to sensitivity analyses excluding data sources in which the data quality was lower and were consistent in analyses stratified by different diabetes definitions. INTERPRETATION: The incidence of diagnosed diabetes is stabilising or declining in many high-income countries. The reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program. |
A prospective comparative study of children with gastroenteritis: emergency department compared with symptomatic care at home
Vanderkooi OG , Xie J , Lee BE , Pang XL , Chui L , Payne DC , MacDonald J , Ali S , MacDonald S , Drews S , Osterreicher L , Kim K , Freedman SB . Eur J Clin Microbiol Infect Dis 2019 38 (12) 2371-2379 Little is known about the epidemiology and severity of gastroenteritis among children treated at home. We sought to compare illness severity and etiology between children brought for emergency department (ED) care to those managed at home (i.e., community). Prospective cohort study of children enrolled between December 2014 and December 2016 in two pediatric EDs in Alberta, Canada along with children treated at home after telephone triage (i.e., community). Primary outcomes were maximal frequency of vomiting and diarrhea in the 24-h pre-enrollment period; secondary outcomes included etiologic pathogens, dehydration severity, future healthcare visits, and treatments provided. A total of 1613 patients (1317 ED, 296 community) were enrolled. Median maximal frequency of vomiting was higher in the ED cohort (5 (3, 10) vs. 5 (2, 8); P < 0.001). Proportion of children with diarrhea and its 24-h median frequency were lower in the ED cohort (61.3 vs. 82.8% and 2 (0, 6) vs. 4 (1, 7); P < 0.001, respectively). In regression analysis, the ED cohort had a higher maximum number of vomiting episodes pre-enrollment (incident rate ratio (IRR) 1.25; 95% CI 1.12, 1.40) while the community cohort had higher maximal 24-h period diarrheal episodes (IRR 1.20; 95% CI 1.01, 1.43). Norovirus was identified more frequently in the community cohort (36.8% vs. 23.6%; P < 0.001). Children treated in the ED have a greater number of vomiting episodes; those treated at home have more diarrheal episodes. Norovirus is more common among children treated symptomatically at home and thus may represent a greater burden of disease than previously thought. |
Infectious disease-specific health literacy in Tibet, China
Yang P , Dunzhu C , Widdowson MA , Wu S , Ciren P , Duoji D , Pingcuo W , Dun B , Ma C , Li J , Pang X , Wang Q . Health Promot Int 2018 33 (1) 84-91 This study was aimed to develop an instrument to assess infectious disease-specific health literacy (IDSHL) in the general population of Tibet, China and identify the association between IDSHL and reported infectious disease-related symptoms. A survey using a standardized questionnaire, which included 25 questions on knowledge, behaviors and skills regarding infectious diseases, was conducted in the general population of Tibet, China between September 2011 and November 2011. The 25 questions formed the index system of the instrument assessing IDSHL (total scores: 25 scores). Factors associated with index scores of IDSHL were identified by general linear model. The association between the index score of IDSHL and the occurrence of the five selected infectious disease symptoms (fever, diarrhea, rash, jaundice or conjunctivitis) were investigated using multivariate unconditional logistic regression. Among 5717 eligible participants in the survey, 4631 participants completed all of the 25 questions in the instrument. The instrument was reliable and valid as measured by the Cronbach's alpha coefficient and split-half coefficient, and the confirmatory factor analysis. Only 1.0% (48/4631) answered >/=80% of the 25 questions correctly (score >/= 20). Significant factors associated with lower health literacy score included female gender, older age, Tibetan group, lower education level, underlying diseases and more undeveloped area. For each increasing score of IDSHL, reports of fever, diarrhea or jaundice in the prior year were significantly decreased by 3% (p = 0.015), 4% (p = 0.004) and 16% (p < 0.001), respectively. Accurately measuring IDSHL could help identify those individuals with poor IDSHL, who could be targeted with specific interventions to improve health. |
Strategic Response to an Outbreak of Circulating Vaccine-Derived Poliovirus Type 2 - Syria, 2017-2018.
Mbaeyi C , Wadood ZM , Moran T , Ather F , Stehling-Ariza T , Nikulin J , Al Safadi M , Iber J , Zomahoun L , Abourshaid N , Pang H , Collins N , Asghar H , Butt OUI , Burns CC , Ehrhardt D , Sharaf M . MMWR Morb Mortal Wkly Rep 2018 67 (24) 690-694 Since the 1988 inception of the Global Polio Eradication Initiative (GPEI), progress toward interruption of wild poliovirus (WPV) transmission has occurred mostly through extensive use of oral poliovirus vaccine (OPV) in mass vaccination campaigns and through routine immunization services (1,2). However, because OPV contains live, attenuated virus, it carries the rare risk for reversion to neurovirulence. In areas with very low OPV coverage, prolonged transmission of vaccine-associated viruses can lead to the emergence of vaccine-derived polioviruses (VDPVs), which can cause outbreaks of paralytic poliomyelitis. Although WPV type 2 has not been detected since 1999, and was declared eradicated in 2015,* most VDPV outbreaks have been attributable to VDPV serotype 2 (VDPV2) (3,4). After the synchronized global switch from trivalent OPV (tOPV) (containing vaccine virus types 1, 2, and 3) to bivalent OPV (bOPV) (types 1 and 3) in April 2016 (5), GPEI regards any VDPV2 emergence as a public health emergency (6,7). During May-June 2017, VDPV2 was isolated from stool specimens from two children with acute flaccid paralysis (AFP) in Deir-ez-Zor governorate, Syria. The first isolate differed from Sabin vaccine virus by 22 nucleotides in the VP1 coding region (903 nucleotides). Genetic sequence analysis linked the two cases, confirming an outbreak of circulating VDPV2 (cVDPV2). Poliovirus surveillance activities were intensified, and three rounds of vaccination campaigns, aimed at children aged <5 years, were conducted using monovalent OPV type 2 (mOPV2). During the outbreak, 74 cVDPV2 cases were identified; the most recent occurred in September 2017. Evidence indicates that enhanced surveillance measures coupled with vaccination activities using mOPV2 have interrupted cVDPV2 transmission in Syria. |
Acetylation by Eis and deacetylation by Rv1151c of Mycobacterium tuberculosis HupB: Biochemical and structural insight
Green KD , Biswas T , Pang AH , Willby MJ , Reed MS , Stuchlik O , Pohl J , Posey JE , Tsodikov OV , Garneau-Tsodikova S . Biochemistry 2018 57 (5) 781-790 Bacterial nucleoid-associated proteins (NAPs) are critical to genome integrity and chromosome maintenance. Post-translational modifications of bacterial NAPs appear to function similarly to their better studied mammalian counterparts. The histone-like NAP HupB from Mycobacterium tuberculosis (Mtb) was previously observed to be acetylated by the acetyltransferase Eis, leading to genome reorganization. We report biochemical and structural aspects of acetylation of HupB by Eis. We also found that the SirT-family NAD(+)-dependent deacetylase Rv1151c from Mtb deacetylated HupB in vitro and characterized the deacetylation kinetics. We propose that activities of Eis and Rv1151c could regulate the acetylation status of HupB to remodel the mycobacterial chromosome in response to environmental changes. |
Global Spread of Norovirus GII.17 Kawasaki 308, 2014-2016
Chan MCW , Hu Y , Chen H , Podkolzin AT , Zaytseva EV , Komano J , Sakon N , Poovorawan Y , Vongpunsawad S , Thanusuwannasak T , Hewitt J , Croucher D , Collins N , Vinjé J , Pang XL , Lee BE , de Graaf M , van Beek J , Vennema H , Koopmans MPG , Niendorf S , Poljsak-Prijatelj M , Steyer A , White PA , Lun JH , Mans J , Hung TN , Kwok K , Cheung K , Lee N , Chan PKS . Emerg Infect Dis 2017 23 (8) 1359-1354 Analysis of complete capsid sequences of the emerging norovirus GII.17 Kawasaki 308 from 13 countries demonstrated that they originated from a single haplotype since the initial emergence in China in late 2014. Global spread of a sublineage SL2 was identified. A new sublineage SL3 emerged in China in 2016. |
Potential impact of B lineage mismatch on trivalent influenza vaccine effectiveness during the 2015-2016 influenza season among nursery school children in Suzhou, China
Wang Y , Chen L , Cheng Y , Zhou S , Pang Y , Zhang J , Greene CM , Song Y , Zhang T , Zhao G . Hum Vaccin Immunother 2017 14 (3) 0 BACKGROUND: We actively followed a cohort of nursery school children in Suzhou, China to assess the impact of vaccination with trivalent influenza vaccine on the prevention of influenza like illness (ILI). METHODS: We enrolled children aged 36 to 72 months from 13 nursery schools in Suzhou starting two weeks after vaccination during October 2015-February 2016. Every school-day, teachers reported the names of students with ILI to study clinicians, who collected the student's nasopharyngeal swab or throat swab, either at a study clinic or the child's home. Swabs were sent to the Suzhou Center for Disease Control and Prevention's laboratory for influenza testing by RT-PCR. RESULTS: In total, 3278 children were enrolled; 83 (3%) were lost to follow-up, while 3195 (vaccinated: 1492, unvaccinated: 1703) were followed for 24 weeks. During the study, 40 samples tested positive; 17 in the vaccinated (B Victoria: 12; A(H1N1)pdm09: 5) and 23 in the unvaccinated group (B Victoria: 10; B Yamagata: 2; A(H1N1)pdm09: 11). The VE estimates were: 16% overall (95%CI:-58%,56%), 48% (-47%,84%) for influenza A(H1N1)pdm09, 43% (-650%,98%) for influenza B Yamagata, and -37% (-227%,42%) for influenza B Victoria. Data were analyzed by vaccinated and unvaccinated groups based on enrollees' vaccination records. CONCLUSIONS: The VE for A(H1N1)pdm09 was moderate but not significant. Mismatching of B lineage may have compromised trivalent influenza vaccine effectiveness during the 2015-2016 influenza season among nursery school children in Suzhou, China. Additional larger studies are warranted to inform policy related to quadrivalent influenza vaccine licensure in China in the future. |
Estimating the full public health value of vaccination
Gessner BD , Kaslow D , Louis J , Neuzil K , O'Brien KL , Picot V , Pang T , Parashar UD , Saadatian-Elahi M , Nelson CB . Vaccine 2017 35 (46) 6255-6263 There is an enhanced focus on considering the full public health value (FPHV) of vaccination when setting priorities, making regulatory decisions and establishing implementation policy for public health activities. Historically, a therapeutic paradigm has been applied to the evaluation of prophylactic vaccines and focuses on an individual benefit-risk assessment in prospective and individually-randomized phase III trials to assess safety and efficacy against etiologically-confirmed clinical outcomes. By contrast, a public health paradigm considers the population impact and encompasses measures of community benefits against a range of outcomes. For example, measurement of the FPHV of vaccination may incorporate health inequity, social and political disruption, disruption of household integrity, school absenteeism and work loss, health care utilization, long-term/on-going disability, the development of antibiotic resistance, and a range of non-etiologically and etiologically defined clinical outcomes. Following an initial conference at the Fondation Merieux in mid-2015, a second conference (December 2016) was held to further describe the efficacy of using the FPHV of vaccination on a variety of prophylactic vaccines. The wider scope of vaccine benefits, improvement in risk assessment, and the need for partnership and coalition building across interventions has also been discussed during the 2014 and 2016 Global Vaccine and Immunization Research Forums and the 2016 Geneva Health Forum, as well as in numerous publications including a special issue of Health Affairs in February 2016. The December 2016 expert panel concluded that while progress has been made, additional efforts will be necessary to have a more fully formulated assessment of the FPHV of vaccines included into the evidence-base for the value proposition and analysis of unmet medical need to prioritize vaccine development, vaccine licensure, implementation policies and financing decisions. The desired outcomes of these efforts to establish an alternative framework for vaccine evaluation are a more robust vaccine pipeline, improved appreciation of vaccine value and hence of its relative affordability, and greater public access and acceptance of vaccines. |
US public sexually transmitted disease clinical services in an era of declining public health funding: 2013-14
Leichliter JS , Heyer K , Peterman TA , Habel MA , Brookmeyer KA , Arnold Pang SS , Stenger MR , Weiss G , Gift TL . Sex Transm Dis 2017 44 (8) 505-509 BACKGROUND: We examined the infrastructure for US public sexually transmitted disease (STD) clinical services. METHODS: In 2013 to 2014, we surveyed 331 of 1225 local health departments (LHDs) who either reported providing STD testing/treatment in the 2010 National Profile of Local Health Departments survey or were the 50 local areas with the highest STD cases or rates. The sample was stratified by jurisdiction population size. We examined the primary referral clinics for STDs, the services offered and the impact of budget cuts (limited to government funding only). Data were analyzed using SAS, and analyses were weighted for nonresponse. RESULTS: Twenty-two percent of LHDs cited a specialty STD clinic as their primary referral for STD services; this increased to 53.5% of LHDs when combination STD-family planning clinics were included. The majority of LHDs (62.8%) referred to clinics providing same-day services. Sexually transmitted disease clinics more frequently offered extragenital testing for chlamydia and/or gonorrhea (74.7%) and gonorrhea culture (68.5%) than other clinics (52.9%, 46.2%, respectively; P < 0.05). The majority of LHDs (61.5%) reported recent budget cuts. Of those with decreased budgets, the most common impacts were fewer clinic hours (42.8%; 95% confidence interval [CI], 24.4-61.2), reduced routine screening (40.2%; 95% CI, 21.7-58.8) and reductions in partner services (42.1%; 95% CI, 23.6-60.7). One quarter of those with reduced STD budgets increased fees or copays for clients. CONCLUSIONS: Findings demonstrate gaps and reductions in US public STD services including clinical services that play an important role in reducing disease transmission. Furthermore, STD clinics tended to offer more specialized STD services than other public clinics. |
Varicella outbreak in a highly-vaccinated school population in Beijing, China during the voluntary two-dose era
Suo L , Lu L , Wang Q , Yang F , Wang X , Pang X , Marin M , Wang C . Vaccine 2017 35 (34) 4368-4373 BACKGROUND: Two-dose varicella vaccination has been available in Beijing since 2012 in the private sector. We investigated a varicella outbreak in a highly vaccinated elementary school population. METHODS: A cohort study was carried out and a varicella case was defined as an acute onset of generalized maculopapulovesicular rash without other apparent cause in a student attending the school from March 29 through May 17, 2015. Breakthrough varicella was defined as varicella >42days after the last vaccine dose among both 1- or 2-dose varicella vaccine recipients. Vaccination information was collected from immunization records; information on prior varicella and clinical presentations was collected by surveying students' parents. RESULTS: Of the 1056 students in the school, 1027 (97.3%) reported no history of varicella. Prior to the outbreak, 98.6% of students had received ≥1 dose of varicella vaccine, and most (63.2%) students received two doses. Twenty varicella cases were identified for an overall attack rate of 2.0%. Half of the cases occurred in the classroom of the index case-patient, a two-dose recipient who was not isolated after symptom onset. Breakthrough varicella accounted for 95% of cases (19/20) with attack rates of 14.3% (1/7), 1.6% (6/362) and 2.0% (13/649) among unvaccinated, one-dose, and two-dose students, respectively. Most case-patients (18/20, 90%) had <50 lesions. No difference in clinical presentations was found between one-dose and two-dose recipients with breakthrough varicella. CONCLUSION: Moderate two-dose varicella vaccine coverage was insufficient to prevent a varicella outbreak. Two-dose recipients with breakthrough varicella are contagious. High two-dose varicella vaccine coverage and timely isolation of cases may be needed for varicella outbreak prevention in the two-dose era. |
A case control study on family history as a risk factor for herpes zoster and associated outcomes, Beijing, China.
Suo L , Lu L , Li J , Sun M , Wang H , Peng X , Yang F , Pang X , Marin M , Wang C . BMC Infect Dis 2017 17 (1) 334 BACKGROUND: Hospital-based case control studies have found family history of herpes zoster (HZ) was associated with risk of HZ, but the role of family history is not fully examined for other HZ-associated outcomes such as recurrent HZ, occurrence of postherpetic neuralgia (PHN), and HZ with different pain severities. METHODS: We conducted a population-based matched case control study. HZ cases that occurred during December 1, 2011 to November 30, 2012 were identified by face-to-face interview with all residents of eight selected communities/villages from three districts of Beijing, China. Medical records were reviewed for those who sought healthcare for HZ. For each case-patient, three, age-matched controls (+/-5 years) without HZ were enrolled from the same community/village of the matched case. Data on family history of HZ were collected by interview and only defined among first-degree relatives. RESULTS: A total of 227 case-patients and 678 matched controls were enrolled. Case-patients were more likely to report a family history of HZ [odds ratio (OR) =2.4, P = 0.002]. Compared with controls, association of family history decreased from HZ with PHN to HZ without PHN (OR = 6.0 and 2.3, respectively; P = 0.002 for trend), from recurrent HZ to primary HZ (OR = 9.4 and 2.2, respectively; P = 0.005 for trend), and from HZ with moderate or severe pain to HZ with mild or no pain (OR = 3.2 and 0.8, respectively; P < 0.001 for trend). CONCLUSIONS: Family history of HZ was associated with HZ occurrence and was more likely in HZ case-patients with PHN, recurrences, and painful HZ. |
The transmission and antibiotic resistance variation in a multiple drug resistance clade of Vibrio cholerae circulating in multiple countries in Asia
Pang B , Du P , Zhou Z , Diao B , Cui Z , Zhou H , Kan B . PLoS One 2016 11 (3) e0149742 Vibrio cholerae has caused massive outbreaks and even trans-continental epidemics. In 2008 and 2010, at least 3 remarkable cholera outbreaks occurred in Hainan, Anhui and Jiangsu provinces of China. To address the possible transmissions and the relationships to the 7th pandemic strains of those 3 outbreaks, we sequenced the whole genomes of the outbreak isolates and compared with the global isolates from the 7th pandemic. The three outbreaks in this study were caused by a cluster of V. cholerae in clade 3.B which is parallel to the clade 3.C that was transmitted from Nepal to Haiti and caused an outbreak in 2010. Pan-genome analysis provided additional evolution information on the mobile element and acquired multiple antibiotic resistance genes. We suggested that clade 3.B should be monitored because the multiple antibiotic resistant characteristics of this clade and the 'amplifier' function of China in the global transmission of current Cholera pandemic. We also show that dedicated whole genome sequencing analysis provided more information than the previous techniques and should be applied in the disease surveillance networks. |
A Large-Scale Community-Based Outbreak of Paratyphoid Fever Caused by Hospital-Derived Transmission in Southern China.
Yan M , Yang B , Wang Z , Wang S , Zhang X , Zhou Y , Pang B , Diao B , Yang R , Wu S , Klena JD , Kan B . PLoS Negl Trop Dis 2015 9 (7) e0003859 BACKGROUND: Since the 1990s, paratyphoid fever caused by Salmonella Paratyphi A has emerged in Southeast Asia and China. In 2010, a large-scale outbreak involving 601 cases of paratyphoid fever occurred in the whole of Yuanjiang county in China. Epidemiological and laboratory investigations were conducted to determine the etiology, source and transmission factors of the outbreak. METHODOLOGY/PRINCIPAL FINDINGS: A case-control study was performed to identify the risk factors for this paratyphoid outbreak. Cases were identified as patients with blood culture-confirmed S. Paratyphi A infection. Controls were healthy persons without fever within the past month and matched to cases by age, gender and geography. Pulsed-field gel electrophoresis and whole-genome sequencing of the S. Paratyphi A strains isolated from patients and environmental sources were performed to facilitate transmission analysis and source tracking. We found that farmers and young adults were the populations mainly affected in this outbreak, and the consumption of raw vegetables was the main risk factor associated with paratyphoid fever. Molecular subtyping and genome sequencing of S. Paratyphi A isolates recovered from improperly disinfected hospital wastewater showed indistinguishable patterns matching most of the isolates from the cases. An investigation showed that hospital wastewater mixed with surface water was used for crop irrigation, promoting a cycle of contamination. After prohibition of the planting of vegetables in contaminated fields and the thorough disinfection of hospital wastewater, the outbreak subsided. Further analysis of the isolates indicated that the origin of the outbreak was most likely from patients outside Yuanjiang county. CONCLUSIONS: This outbreak is an example of the combined effect of social behaviors, prevailing ecological conditions and improper disinfection of hospital wastewater on facilitating a sustained epidemic of paratyphoid fever. This study underscores the critical need for strict treatment measures of hospital wastewater and the maintenance of independent agricultural irrigation systems in rural areas. |
Mortality hazard and survival after tuberculosis treatment
Miller TL , Wilson FA , Pang JW , Beavers S , Hoger S , Sharnprapai S , Pagaoa M , Katz DJ , Weis SE . Am J Public Health 2015 105 (5) e1-e8 OBJECTIVES: We compared mortality among tuberculosis (TB) survivors and a similar population. METHODS: We used local health authority records from 3 US sites to identify 3853 persons who completed adequate treatment of TB and 7282 individuals diagnosed with latent TB infection 1993 to 2002. We then retrospectively observed mortality after 6 to 16 years of observation. We ascertained vital status as of December 31, 2008, using the Centers for Disease Control and Prevention's National Death Index. We analyzed mortality rates, hazards, and associations using Cox regression. RESULTS: We traced 11 135 individuals over 119 772 person-years of observation. We found more all-cause deaths (20.7% vs 3.1%) among posttreatment TB patients than among the comparison group, an adjusted average excess of 7.6 deaths per 1000 person-years (8.8 vs 1.2; P < .001). Mortality among posttreatment TB patients varied with observable factors such as race, site of disease, HIV status, and birth country. CONCLUSIONS: Fully treated TB is still associated with substantial mortality risk. Cure as currently understood may be insufficient protection against TB-associated mortality in the years after treatment, and TB prevention may be a valuable opportunity to modify this risk. |
Epidemiology of tuberculosis in young children in the United States
Pang J , Teeter LD , Katz DJ , Davidow AL , Miranda W , Wall K , Ghosh S , Stein-Hart T , Restrepo BI , Reves R , Graviss EA . Pediatrics 2014 133 (3) e494-504 OBJECTIVES: To estimate tuberculosis (TB) rates among young children in the United States by children's and parents' birth origins and describe the epidemiology of TB among young children who are foreign-born or have at least 1 foreign-born parent. METHODS: Study subjects were children <5 years old diagnosed with TB in 20 US jurisdictions during 2005-2006. TB rates were calculated from jurisdictions' TB case counts and American Community Survey population estimates. An observational study collected demographics, immigration and travel histories, and clinical and source case details from parental interviews and health department and TB surveillance records. RESULTS: Compared with TB rates among US-born children with US-born parents, rates were 32 times higher in foreign-born children and 6 times higher in US-born children with foreign-born parents. Most TB cases (53%) were among the 29% of children who were US born with foreign-born parents. In the observational study, US-born children with foreign-born parents were more likely than foreign-born children to be infants (30% vs 7%), Hispanic (73% vs 37%), diagnosed through contact tracing (40% vs 7%), and have an identified source case (61% vs 19%); two-thirds of children were exposed in the United States. CONCLUSIONS: Young children who are US born of foreign-born parents have relatively high rates of TB and account for most cases in this age group. Prompt diagnosis and treatment of adult source cases, effective contact investigations prioritizing young contacts, and targeted testing and treatment of latent TB infection are necessary to reduce TB morbidity in this population. |
Epidemiology of human infections with avian influenza A(H7N9) virus in China
Li Q , Zhou L , Zhou M , Chen Z , Li F , Wu H , Xiang N , Chen E , Tang F , Wang D , Meng L , Hong Z , Tu W , Cao Y , Li L , Ding F , Liu B , Wang M , Xie R , Gao R , Li X , Bai T , Zou S , He J , Hu J , Xu Y , Chai C , Wang S , Gao Y , Jin L , Zhang Y , Luo H , Yu H , Gao L , Pang X , Liu G , Shu Y , Yang W , Uyeki TM , Wang Y , Wu F , Feng Z . N Engl J Med 2013 370 (6) 520-32 BACKGROUND: The first identified cases of avian influenza A (H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to characterize the epidemiologic characteristics of H7N9 cases in China as of April 17, 2013. METHODS: Field investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts in whom symptoms developed and were tested for the presence of the H7N9 virus testing by means of real-time RT-PCR. RESULTS: Among 82 persons with confirmed H7N9 virus infection, the median age was 63 years (range, 2 to 89), 73% were male, and 84% were urban residents. Confirmed cases occurred in six areas of China. Of 77 persons with available data, 4 were poultry workers, and 77% had a history of exposure to live animals, including chickens (76%). A total of 17 persons (21%) died after a median duration of illness of 11 days, 60 remain critically ill, and 4 with clinically mild cases were discharged from the hospital; 1 pediatric patient was not admitted to the hospital. In two family clusters, human-to-human transmission of H7N9 virus could not be ruled out. A total of 1251 of the 1689 close contacts of case patients completed the monitoring period; respiratory symptoms developed in 19 of them (1.5%), all of whom tested negative for the H7N9 virus. CONCLUSIONS: Most persons with confirmed H7N9 virus infection were critically ill and epidemiologically unrelated. Laboratory-confirmed human-to-human H7N9 virus transmission was not documented among close contacts, but such transmission could not be ruled out in two families. |
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