Last data update: May 06, 2024. (Total: 46732 publications since 2009)
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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 seroprevalence and longitudinal antibody response following natural infection in pregnancy: a prospective cohort study (preprint)
Drake AL , Escudero JN , Aurelio MC , Ellington SR , Zapata LB , Galang RR , Snead MC , Yamamoto K , Salerno C , Richardson BA , Greninger AL , Kachikis AB , Englund JA , LaCourse SM . medRxiv 2022 30 Importance: Antenatal care provides unique opportunities to assess SARS-CoV-2 seroprevalence and antibody response duration after natural infection detected during pregnancy; transplacental antibody transfer may inform peripartum and neonatal protection. Objective(s): Estimate seroprevalence and durability of antibodies from natural infection (anti-nucleocapsid (anti-N) IgG) among pregnant people, and evaluate transplacental transfer efficiency. Design(s): Seroprevalence study: cross-sectional SARS-CoV-2 antibody screening among pregnant people December 9, 2020-June 19, 2021. Cohort study: Pregnant people screened anti-N IgG+ by Abbott Architect chemiluminescent immunoassay in seroprevalence study or identified through medical records with RT-PCR+ or antigen positive results enrolled in a prospective cohort December 9, 2020-June 30, 2022 to longitudinally measure anti-N IgG responses. We collected cord blood and assessed transplacental transfer of maternally-derived anti-N antibodies. Setting(s): Three hospitals and 14 affiliated clinics providing antenatal and delivery care, Seattle, Washington metropolitan area. Participant(s): Seroprevalence study: pregnant people were screened for SAR-CoV-2 anti-N IgG during routine care. Cohort study: Pregnant people with evidence of prior SARS-CoV-2 infection (screened anti-N IgG+ from seroprevalence study or identified with a RT-PCR+ or antigen positive result from medical records) were enrolled in a cohort study to longitudinally measure anti-N IgG responses. Exposure(s) (for observational studies): COVID-19 diagnosis, symptoms, and disease severity. Main Outcome(s) and Measure(s): Presence and durability of SARS-CoV-2 anti-N IgG, transplacental transfer of maternally-derived anti-N IgG. Result(s): Of 1289 pregnant people screened in the seroprevalence study, 5% (65) tested SARS-CoV-2 anti-N IgG+, including 39 (60%) without prior RT-PCR+ or antigen positive results and 53 (82%) without symptoms. Among 89 participants enrolled in the cohort study, 73 (82%) had anti-N IgG+ results during pregnancy. Among 49 participants with delivery samples 33 (67%) were anti-N IgG negative by delivery. Of 24 remaining anti-N IgG+ at delivery with paired cord blood samples, 12 (50%) had efficient transplacental anti-N IgG antibody transfer. Median time from first anti-N IgG to below positive antibody threshold was 17 weeks and did not differ by prior RT-PCR+ or antigen positive status. Conclusions and Relevance: Maternally-derived SARS-CoV-2 antibodies to natural infection may wane before delivery. Vaccines are recommended for pregnant persons to reduce severe illness and confer protection to infants. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
National burden of influenza-associated hospitalizations in Cambodia, 2015 and 2016
Ieng V , Tolosa MX , Tek B , Sar B , Sim K , Seng H , Thyl M , Dara C , Moniborin M , Stewart RJ , Bell LC , Theocharopoulos G , Chin S , Chau D , Iuliano AD , Moen A , Tsuyuoka R , Dueger EL , Sullivan SG , Ly S . Western Pac Surveill Response J 2018 9 44-52 INTRODUCTION: The burden of influenza in Cambodia is not well known, but it would be useful for understanding the impact of seasonal epidemics and pandemics and to design appropriate policies for influenza prevention and control. The severe acute respiratory infection (SARI) surveillance system in Cambodia was used to estimate the national burden of SARI hospitalizations in Cambodia. METHODS: We estimated age-specific influenza-associated SARI hospitalization rates in three sentinel sites in Svay Rieng, Siem Reap and Kampong Cham provinces. We used influenza-associated SARI surveillance data for one year to estimate the numerator and hospital admission surveys to estimate the population denominator for each site. A national influenza-associated SARI hospitalization rate was calculated using the pooled influenza-associated SARI hospitalizations for all sites as a numerator and the pooled catchment population of all sites as denominator. National influenza-associated SARI case counts were estimated by applying hospitalization rates to the national population. RESULTS: The national annual rates of influenza-associated hospitalizations per 100 000 population was highest for the two youngest age groups at 323 for < 1 year and 196 for 1-4 years. We estimated 7547 influenza-associated hospitalizations for Cambodia with almost half of these represented by children younger than 5 years. DISCUSSION: We present national estimates of influenza-associated SARI hospitalization rates for Cambodia based on sentinel surveillance data from three sites. The results of this study indicate that the highest burden of severe influenza infection is borne by the younger age groups. These findings can be used to guide future strategies to reduce influenza morbidity. |
Genomic epidemiology of SARS-CoV-2 in Cambodia, January 2020 to February 2021.
Su YCF , Ma JZJ , Ou TP , Pum L , Krang S , Raftery P , Kinzer MH , Bohl J , Ieng V , Kab V , Patel S , Sar B , Ying WF , Jayakumar J , Horm VS , Boukli N , Yann S , Troupin C , Heang V , Garcia-Rivera JA , Sengdoeurn Y , Heng S , Lay S , Chea S , Darapheak C , Savuth C , Khalakdina A , Ly S , Baril L , Manning JE , Simone-Loriere E , Duong V , Dussart P , Sovann L , Smith GJD , Karlsson EA . Virus Evol 2023 9 (1) veac121 The first case of coronavirus disease 2019 (COVID-19) in Cambodia was confirmed on 27 January 2020 in a traveller from Wuhan. Cambodia subsequently implemented strict travel restrictions, and although intermittent cases were reported during the first year of the COVID-19 pandemic, no apparent widespread community transmission was detected. Investigating the routes of severe acute respiratory coronavirus 2 (SARS-CoV-2) introduction into the country was critical for evaluating the implementation of public health interventions and assessing the effectiveness of social control measures. Genomic sequencing technologies have enabled rapid detection and monitoring of emerging variants of SARS-CoV-2. Here, we detected 478 confirmed COVID-19 cases in Cambodia between 27 January 2020 and 14 February 2021, 81.3 per cent in imported cases. Among them, fifty-four SARS-CoV-2 genomes were sequenced and analysed along with representative global lineages. Despite the low number of confirmed cases, we found a high diversity of Cambodian viruses that belonged to at least seventeen distinct PANGO lineages. Phylogenetic inference of SARS-CoV-2 revealed that the genetic diversity of Cambodian viruses resulted from multiple independent introductions from diverse regions, predominantly, Eastern Asia, Europe, and Southeast Asia. Most cases were quickly isolated, limiting community spread, although there was an A.23.1 variant cluster in Phnom Penh in November 2020 that resulted in a small-scale local transmission. The overall low incidence of COVID-19 infections suggests that Cambodia's early containment strategies, including travel restrictions, aggressive testing and strict quarantine measures, were effective in preventing large community outbreaks of COVID-19. |
Test-to-Stay Implementation in Four Pre-K-12 School Districts.
Lammie SL , Ford L , Swanson M , Guinn AS , Kamitani E , van Zyl A , Rose CE , Marynak K , Shields J , Donovan CV , Holman EJ , Mark-Carew M , Welton M , Thomas ES , Neatherlin J . Pediatrics 2022 150 (4) OBJECTIVE: Globally, COVID-19 has affected how children learn. We evaluated the impact of Test to Stay (TTS) on secondary and tertiary transmission of SARS-CoV-2 and potential impact on in-person learning in four school districts in the United States from September 13-November 19, 2021. METHODS: Implementation of TTS varied across school districts. Data on index cases, school-based close contacts, TTS participation, and testing results were obtained from four school districts in diverse geographic regions. Descriptive statistics, secondary and tertiary attack risk, and a theoretical estimate of impact on in-person learning were calculated. RESULTS: Fifty-one schools in four school districts reported 374 COVID-19 index cases and 2,520 school-based close contacts eligible for TTS. The proportion participating in TTS ranged from 22%-79%. By district, the secondary attack risk (SAR) and tertiary attack risk (TAR) among TTS participants ranged between 2.2%-11.1% and 0%-17.6%, respectively. Nine clusters were identified among secondary cases and two among tertiary cases. The theoretical maximum number of days of in-person learning saved by using TTS was 976-4,650 days across jurisdictions. CONCLUSIONS: TTS preserves in-person learning days. Decisions to participate in TTS may have been influenced by ease of access to testing, communication between schools and families, testing logistics, and school resources. TAR determination became more complicated when numbers of close contacts increased. Minimizing exposure through continued implementation of layered prevention strategies is imperative. To ensure adequate resources for implementation of TTS, community transmission levels should be considered. |
SARS-CoV-2 incidence, transmission, and reinfection in a rural and an urban setting: results of the PHIRST-C cohort study, South Africa, 2020-21.
Cohen C , Kleynhans J , von Gottberg A , McMorrow ML , Wolter N , Bhiman JN , Moyes J , du Plessis M , Carrim M , Buys A , Martinson NA , Kahn K , Tollman S , Lebina L , Wafawanaka F , du Toit JD , Gómez-Olivé FX , Dawood FS , Mkhencele T , Sun K , Viboud C , Tempia S . Lancet Infect Dis 2022 22 (6) 821-834 BACKGROUND: By August, 2021, South Africa had been affected by three waves of SARS-CoV-2; the second associated with the beta variant and the third with the delta variant. Data on SARS-CoV-2 burden, transmission, and asymptomatic infections from Africa are scarce. We aimed to evaluate SARS-CoV-2 burden and transmission in one rural and one urban community in South Africa. METHODS: We conducted a prospective cohort study of households in Agincourt, Mpumalanga province (rural site) and Klerksdorp, North West province (urban site) from July, 2020 to August, 2021. We randomly selected households for the rural site from a health and sociodemographic surveillance system and for the urban site using GPS coordinates. Households with more than two members and where at least 75% of members consented to participate were eligible. Midturbinate nasal swabs were collected twice a week from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time RT-PCR (RT-rtPCR). Serum was collected every 2 months and tested for anti-SARS-CoV-2 antibodies. Main outcomes were the cumulative incidence of SARS-CoV-2 infection, frequency of reinfection, symptomatic fraction (percent of infected individuals with ≥1 symptom), the duration of viral RNA shedding (number of days of SARS-CoV-2 RT-rtPCR positivity), and the household cumulative infection risk (HCIR; number of infected household contacts divided by the number of susceptible household members). FINDINGS: 222 households (114 at the rural site and 108 at the urban site), and 1200 household members (643 at the rural site and 557 at the urban site) were included in the analysis. For 115 759 nasal specimens from 1200 household members (follow-up 92·5%), 1976 (1·7%) were SARS-CoV-2-positive on RT-rtPCR. By RT-rtPCR and serology combined, 749 of 1200 individuals (62·4% [95% CI 58·1-66·4]) had at least one SARS-CoV-2 infection episode, and 87 of 749 (11·6% [9·4-14·2]) were reinfected. The mean infection episode duration was 11·6 days (SD 9·0; range 4-137). Of 662 RT-rtPCR-confirmed episodes (>14 days after the start of follow-up) with available data, 97 (14·7% [11·9-17·9]) were symptomatic with at least one symptom (in individuals aged <19 years, 28 [7·5%] of 373 episodes symptomatic; in individuals aged ≥19 years, 69 [23·9%] of 289 episodes symptomatic). Among 222 households, 200 (90·1% [85·3-93·7]) had at least one SARS-CoV-2-positive individual on RT-rtPCR or serology. HCIR overall was 23·9% (195 of 817 susceptible household members infected [95% CI 19·8-28·4]). HCIR was 23·3% (20 of 86) for symptomatic index cases and 23·9% (175 of 731) for asymptomatic index cases (univariate odds ratio [OR] 1·0 [95% CI 0·5-2·0]). On multivariable analysis, accounting for age and sex, low minimum cycle threshold value (≤30 vs >30) of the index case (OR 5·3 [2·3-12·4]) and beta and delta variant infection (vs Wuhan-Hu-1, OR 3·3 [1·4-8·2] and 10·4 [4·1-26·7], respectively) were associated with increased HCIR. People living with HIV who were not virally supressed (≥400 viral load copies per mL) were more likely to develop symptomatic illness when infected with SAR-CoV-2 (OR 3·3 [1·3-8·4]), and shed SARS-CoV-2 for longer (hazard ratio 0·4 [95% CI 0·3-0·6]) compared with HIV-uninfected individuals. INTERPRETATION: In this study, 565 (85·3%) SARS-CoV-2 infections were asymptomatic and index case symptom status did not affect HCIR, suggesting a limited role for control measures targeting symptomatic individuals. Increased household transmission of beta and delta variants was likely to have contributed to successive waves of SARS-CoV-2 infection, with more than 60% of individuals infected by the end of follow-up. FUNDING: US CDC, South Africa National Institute for Communicable Diseases, and Wellcome Trust. |
Human infection with avian influenza A(H9N2) virus, Cambodia, February 2021
Um S , Siegers JY , Sar B , Chin S , Patel S , Bunnary S , Hak M , Sor S , Sokhen O , Heng S , Chau D , Sothyra T , Khalakdina A , Mott JA , Olsen SJ , Claes F , Sovann L , Karlsson EA . Emerg Infect Dis 2021 27 (10) 2742-2745 In February 2021, routine sentinel surveillance for influenza-like illness in Cambodia detected a human avian influenza A(H9N2) virus infection. Investigations identified no recent H9N2 virus infections in 43 close contacts. One chicken sample from the infected child's house was positive for H9N2 virus and genetically similar to the human virus. |
SARS-CoV-2 transmission in a Georgia school district - United States, December 2020-January 2021.
Gettings JR , Gold JAW , Kimball A , Forsberg K , Scott C , Uehara A , Tong S , Hast M , Swanson MR , Morris E , Oraka E , Almendares O , Thomas ES , Mehari L , McCloud J , Roberts G , Crosby D , Balajee A , Burnett E , Chancey RJ , Cook P , Donadel M , Espinosa C , Evans ME , Fleming-Dutra KE , Forero C , Kukielka EA , Li Y , Marcet PL , Mitruka K , Nakayama JY , Nakazawa Y , O'Hegarty M , Pratt C , Rice ME , Rodriguez Stewart RM , Sabogal R , Sanchez E , Velasco-Villa A , Weng MK , Zhang J , Rivera G , Parrott T , Franklin R , Memark J , Drenzek C , Hall AJ , Kirking HL , Tate JE , Vallabhaneni S . Clin Infect Dis 2021 74 (2) 319-326 BACKGROUND: To inform prevention strategies, we assessed the extent of SARS-CoV-2 transmission and settings in which transmission occurred in a Georgia public school district. METHODS: During December 1, 2020-January 22, 2021, SARS-CoV-2-infected index cases and their close contacts in schools were identified by school and public health officials. For in-school contacts, we assessed symptoms and offered SARS-CoV-2 RT-PCR testing; performed epidemiologic investigations and whole-genome sequencing to identify in-school transmission; and calculated secondary attack rate (SAR) by school setting (e.g., sports, elementary school classroom), index case role (i.e., staff, student), and index case symptomatic status. RESULTS: We identified 86 index cases and 1,119 contacts, 688 (63.1%) of whom received testing. Fifty-nine (8.7%) of 679 contacts tested positive; 15 (17.4%) of 86 index cases resulted in ≥2 positive contacts. Among 55 persons testing positive with available symptom data, 31 (56.4%) were asymptomatic. Highest SAR were in indoor, high-contact sports settings (23.8%, 95% confidence interval [CI] 12.7, 33.3), staff meetings/lunches (18.2%, CI 4.5-31.8), and elementary school classrooms (9.5%, CI 6.5-12.5). SAR was higher for staff (13.1%, CI 9.0-17.2) versus student index cases (5.8%, CI 3.6-8.0) and for symptomatic (10.9%, CI 8.1-13.9) versus asymptomatic index cases (3.0%, CI 1.0-5.5). CONCLUSIONS: Indoor sports may pose a risk to the safe operation of in-person learning. Preventing infection in staff members, through measures that include COVID-19 vaccination, is critical to reducing in-school transmission. Because many positive contacts were asymptomatic, contact tracing should be paired with testing, regardless of symptoms. |
Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis
Lafond KE , Porter RM , Whaley MJ , Suizan Z , Ran Z , Aleem MA , Thapa B , Sar B , Proschle VS , Peng Z , Feng L , Coulibaly D , Nkwembe E , Olmedo A , Ampofo W , Saha S , Chadha M , Mangiri A , Setiawaty V , Ali SS , Chaves SS , Otorbaeva D , Keosavanh O , Saleh M , Ho A , Alexander B , Oumzil H , Baral KP , Huang QS , Adebayo AA , Al-Abaidani I , von Horoch M , Cohen C , Tempia S , Mmbaga V , Chittaganpitch M , Casal M , Dang DA , Couto P , Nair H , Bresee JS , Olsen SJ , Azziz-Baumgartner E , Nuorti JP , Widdowson MA . PLoS Med 2021 18 (3) e1003550 BACKGROUND: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. METHODS AND FINDINGS: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. CONCLUSIONS: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide. |
An influenza A(H3N2) virus outbreak during the COVID-19 pandemic, Kingdom of Cambodia, 2020.
Sovann L , Sar B , Kab V , Yann S , Kinzer M , Raftery P , Albalak R , Patel S , Long Hay P , Seng H , Um S , Chin S , Chau D , Khalakdina A , Karlsson E , Olsen SJ , Mott JA . Int J Infect Dis 2020 103 352-357 BACKGROUND: Coinciding with the COVID-19 pandemic, global influenza virus circulation decreased, possibly due to widespread community mitigation measures. Cambodia eased some COVID-19 mitigation measures in June and July 2020. On Aug 20th a cluster of respiratory illnesses among residents of a pagoda included persons that had tested positive for influenza A, and none that were positive for SARS-CoV-2. METHODS: On Aug 25, a response team deployed. Persons with influenza-like illness (ILI) were asked questions on demographics, illness, personal prevention measures, and residential arrangements. Respiratory swabs were tested for influenza and SARS-Cov-2 by RT-PCR; viruses were sequenced. Sentinel surveillance data were analyzed to assess recent trends in influenza circulation in the community. RESULTS: Influenza A(H3N2) viruses were identified in sentinel surveillance in Cambodia in July 2020, prior to the reported pagoda outbreak. Among the 362 pagoda residents, 73(20.2%) ILI cases were identified; 40 were tested with 33/40 (82.5%) confirmed positive for influenza A(H3N2). All 40 were negative for SARS-CoV-2. Among 73 residents with ILI, none were vaccinated against influenza, 47 (64%) clustered in 3 of 8 sleeping quarters; 20 (27%) reported often wearing a mask; 27 (36%) reported often washing hands; and 11 (15%) reported practicing social distancing. All viruses clustered within clade 3c2.A1 close to strains circulating in Australia in 2020. CONCLUSIONS: Circulation of influenza viruses began in the community following a relaxing of national COVID-19 mitigation measures, and prior to this outbreak in a pagoda with limited social distancing. Continued surveillance and influenza vaccination remain needed to limit the impact of influenza globally. |
Severe Coronavirus Infections in Pregnancy: A Systematic Review.
Galang RR , Chang K , Strid P , Snead MC , Woodworth KR , House LD , Perez M , Barfield WD , Meaney-Delman D , Jamieson DJ , Shapiro-Mendoza CK , Ellington SR . Obstet Gynecol 2020 136 (2) 262-272 OBJECTIVE: To inform the current coronavirus disease 2019 (COVID-19) outbreak, we conducted a systematic literature review of case reports of Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, during pregnancy and summarized clinical presentation, course of illness, and pregnancy and neonatal outcomes. DATA SOURCES: We searched MEDLINE and ClinicalTrials.gov from inception to April 23, 2020. METHODS OF STUDY SELECTION: We included articles reporting case-level data on MERS-CoV, SARS-CoV, and SARS-CoV-2 infection in pregnant women. Course of illness, indicators of severe illness, maternal health outcomes, and pregnancy outcomes were abstracted from included articles. TABULATION, INTEGRATION, AND RESULTS: We identified 1,328 unique articles, and 1,253 articles were excluded by title and abstract review. We completed full-text review on 75, and 29 articles were excluded by full-text review. Among 46 publications reporting case-level data, eight described 12 cases of MERS-CoV infection, seven described 17 cases of SARS-CoV infection, and 31 described 98 cases of SARS-CoV-2 infection. Clinical presentation and course of illness ranged from asymptomatic to severe fatal disease, similar to the general population of patients. Severe morbidity and mortality among women with MERS-CoV, SARS-CoV, or SARS-CoV-2 infection in pregnancy and adverse pregnancy outcomes, including pregnancy loss, preterm delivery, and laboratory evidence of vertical transmission, were reported. CONCLUSION: Understanding whether pregnant women may be at risk for adverse maternal and neonatal outcomes from severe coronavirus infections is imperative. Data from case reports of SARS-CoV, MERS-CoV, and SAR-CoV-2 infections during pregnancy are limited, but they may guide early public health actions and clinical decision-making for COVID-19 until more rigorous and systematically collected data are available. The capture of critical data is needed to better define how this infection affects pregnant women and neonates. This review was not registered with PROSPERO. |
From H5N1 to HxNy: An epidemiologic overview of human infections with avian influenza in the Western Pacific Region, 2003-2017
Hamid S , Arima Y , Dueger E , Konings F , Bell L , Lee CK , Luo D , Otsu S , Olowokure B , Li A . Western Pac Surveill Response J 2018 9 53-67 Since the first confirmed human infection with avian influenza A(H5N1) virus was reported in Hong Kong Special Administrative Region SAR (China) in 1997, sporadic zoonotic avian influenza viruses causing human illness have been identified globally with the World Health Organization (WHO) Western Pacific Region as a hotspot. A resurgence of A(H5N1) occurred in humans and animals in November 2003. Between November 2003 and September 2017, WHO received reports of 1838 human infections with avian influenza viruses A(H5N1), A(H5N6), A(H6N1), A(H7N9), A(H9N2) and A(H10N8) in the Western Pacific Region. Most of the infections were with A(H7N9) (n = 1562, 85%) and A(H5N1) (n = 238, 13%) viruses, and most (n = 1583, 86%) were reported from December through April. In poultry and wild birds, A(H5N1) and A(H5N6) subtypes were the most widely distributed, with outbreaks reported from 10 and eight countries and areas, respectively. |
Probing the effects of pyrimidine functional group switches on acyclic fleximer analogues for antiviral activity
Yates MK , Chatterjee P , Flint M , Arefeayne Y , Makuc D , Plavec J , Spiropoulou CF , Seley-Radtke KL . Molecules 2019 24 (17) Due to their ability to inhibit viral DNA or RNA replication, nucleoside analogues have been used for decades as potent antiviral therapeutics. However, one of the major limitations of nucleoside analogues is the development of antiviral resistance. In that regard, flexible nucleoside analogues known as "fleximers" have garnered attention over the years due to their ability to survey different amino acids in enzyme binding sites, thus overcoming the potential development of antiviral resistance. Acyclic fleximers have previously demonstrated antiviral activity against numerous viruses including Middle East Respiratory Syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and, most recently, flaviviruses such as Dengue (DENV) and Yellow Fever Virus (YFV). Due to these interesting results, a Structure Activity Relationship (SAR) study was pursued in order to analyze the effect of the pyrimidine functional group and acyl protecting group on antiviral activity, cytotoxicity, and conformation. The results of those studies are presented herein. |
Circulation and characterization of seasonal influenza viruses in Cambodia, 2012-2015
Horwood PF , Karlsson EA , Horm SV , Ly S , Heng S , Chin S , Darapheak C , Saunders D , Chanthap L , Rith S , Y P , Chea KL , Sar B , Parry A , Ieng V , Tsuyouka R , Deng YM , Hurt AC , Barr IG , Komadina N , Buchy P , Dussart P . Influenza Other Respir Viruses 2019 13 (5) 465-476 BACKGROUND: Influenza virus circulation is monitored through the Cambodian influenza-like illness (ILI) sentinel surveillance system and isolates are characterized by the National Influenza Centre (NIC). Seasonal influenza circulation has previously been characterized by year-round activity and a peak during the rainy season (June-November). OBJECTIVES: We documented the circulation of seasonal influenza in Cambodia for 2012-2015 and investigated genetic, antigenic, and antiviral resistance characteristics of influenza isolates. PATIENTS/METHODS: Respiratory samples were collected from patients presenting with influenza-like illness (ILI) at 11 hospitals throughout Cambodia. First-line screening was conducted by the National Institute of Public Health and the Armed Forces Research Institute of Medical Sciences. Confirmation of testing and genetic, antigenic and antiviral resistance characterization was conducted by Institute Pasteur in Cambodia, the NIC. Additional virus characterization was conducted by the WHO Collaborating Centre for Reference and Research on Influenza (Melbourne, Australia). RESULTS: Between 2012 and 2015, 1,238 influenza-positive samples were submitted to the NIC. Influenza A(H3N2) (55.3%) was the dominant subtype, followed by influenza B (30.9%; predominantly B/Yamagata-lineage) and A(H1N1)pdm09 (13.9%). Circulation of influenza viruses began earlier in 2014 and 2015 than previously described, coincident with the emergence of A(H3N2) clades 3C.2a and 3C.3a, respectively. There was high diversity in the antigenicity of A(H3N2) viruses, and to a smaller extent influenza B viruses, during this period, with some mismatches with the northern and southern hemisphere vaccine formulations. All isolates tested were susceptible to the influenza antiviral drugs oseltamivir and zanamivir. CONCLUSIONS: Seasonal and year-round co-circulation of multiple influenza types/subtypes were detected in Cambodia during 2012-2015. |
Antimicrobial resistance in Cambodia: a review
Reed TAN , Krang S , Miliya T , Townell N , Letchford J , Bun S , Sar B , Osbjer K , Seng S , Chou M , By Y , Vanchinsuren L , Nov V , Chau D , Phe T , de Lauzanne A , Ly S , Turner P . Int J Infect Dis 2019 85 98-107 OBJECTIVES: Following the launch of the Global Antimicrobial Resistance Surveillance System (GLASS), antimicrobial resistance (AMR) rates in many countries remain poorly described. This review provides an overview of published AMR data from Cambodia in the context of recently initiated national human and food-animal surveillance. METHODS: PubMed and the Cochrane Database of Systematic Reviews were searched for articles published from 2000 to 2018, which reported antimicrobial susceptibility testing (AST) data for GLASS specific organisms isolated from Cambodia. Articles were screened using strict inclusion/exclusion criteria. AST data was extracted, with medians and ranges of resistance rates calculated for specific bug-drug combinations. RESULTS: Twenty-four papers were included for final analysis, with 20 describing isolates from human populations. Escherichia coli was the most commonly described organism, with median resistance rates from human isolates of 92.8% (n=6 articles), 46.4% (n=4), 55.4% (n=8), and 46.4% (n=5) to ampicillin, 3(rd) generation cephalosporins, fluoroquinolones, and gentamicin respectively. CONCLUSIONS: Whilst resistance rates are high for several GLASS organisms, there were insufficient data to draw robust conclusions about the AMR situation in Cambodia. The recently implemented national AMR surveillance systems will begin to address this data gap. |
Analysis of IgG anti-HEV antibody protective levels during hepatitis E virus reinfection in experimentally infected rhesus macaques
Choi Y , Zhang X , Skinner B . J Infect Dis 2018 219 (6) 916-924 Background: Secondary spread of hepatitis E virus (HEV) infection occurs often in endemic settings in developing countries. The host immune signatures contributing to protection against subsequent HEV reinfection are unknown. Methods: Twelve seroconverted rhesus macaques were re-inoculated with homologous HEV genotype 1 (gt1, Sar-55) and followed for 115 days. HEV RNA, HEV-specific T-cell responses, IgG anti-HEV antibody, and the IgG anti-HEV avidity index were tested. Results: Four animals with baseline IgG anti-HEV levels from 1.5 to 13.4 WHO U/ml evidenced reinfection as determined by HEV RNA in stool, and increase in IgG anti-HEV levels between 63- and 285-fold (P= 0.003). Eight animals with baseline IgG anti-HEV levels from 2.8 to 90.7 WHO U/ml did not develop infection or shed virus in feces, and IgG anti-HEV antibody levels were unchanged (P= 0.017). The four reinfected animals showed a lower HEV-IgG avidity index (average 35.5%) than the 8 protected animals (average 62.1%). HEV-specific IFN- producing T cells were 2-fold higher in reinfected animals (P= 0.018). Conclusions: Pre-existing antibody and high IgG avidity index (>50%) are important factors for protection against HEV reinfection. HEV-specific T cell responses were elevated in reinfected animals after subsequent exposure to HEV. |
Using a hospital admission survey to estimate the burden of influenza-associated severe acute respiratory infection in one province of Cambodia - methods used and lessons learned
Stewart RJ , Ly S , Sar B , Ieng V , Heng S , Sim K , Machingaidze C , Roguski K , Dueger E , Moen A , Tsuyuoka R , Iuliano AD . Influenza Other Respir Viruses 2018 12 (1) 104-112 BACKGROUND: Understanding the burden of influenza-associated severe acute respiratory infection (SARI) is important for setting national influenza surveillance and vaccine priorities. Estimating influenza-associated SARI rates requires hospital-based surveillance data and a population-based denominator, which can be challenging to determine. OBJECTIVES: We present an application of the World Health Organization's recently developed manual (WHO Manual) including hospital admission survey (HAS) methods for estimating the burden of influenza-associated SARI, with lessons learned to help others calculate similar estimates. METHODS: Using an existing SARI surveillance platform in Cambodia, we counted influenza-associated SARI cases during 2015 at one sentinel surveillance site in Svay Rieng Province. We applied WHO Manual-derived methods to count respiratory hospitalizations at all hospitals within the catchment area, where 95% of the sentinel site case-patients resided. We used HAS methods to adjust the district-level population denominator for the sentinel site and calculated the incidence rate of influenza-associated SARI by dividing the number of influenza-positive SARI infections by the adjusted population denominator and multiplying by 100 000. We extrapolated the rate to the provincial population to derive a case count for 2015. We evaluated data sources, detailed steps of implementation, and identified lessons learned. RESULTS: We estimated an adjusted influenza-associated 2015 SARI rate of 13.5/100 000 persons for the catchment area of Svay Rieng Hospital and 77 influenza-associated SARI cases in Svay Rieng Province after extrapolation. CONCLUSIONS: Methods detailed in the WHO Manual and operationalized successfully in Cambodia can be used in other settings to estimate rates of influenza-associated SARI. |
The unwelcome houseguest: secondary household transmission of norovirus
Marsh ZA , Grytdal SP , Beggs JC , Leshem E , Gastanaduy PA , Rha B , Nyaku M , Lopman BA , Hall AJ . Epidemiol Infect 2017 146 (2) 1-9 Norovirus is the leading cause of acute gastroenteritis in the USA. Although secondary household transmission of norovirus is frequently reported in outbreaks, little is known about specific risk factors for susceptibility and infectiousness in the household. Three norovirus outbreaks were investigated and data were collected on individuals exposed in the primary outbreak setting and their household members. Potential individual- and household-level risk factors for susceptibility and infectiousness were assessed using univariate and multivariate generalised linear mixed models. In the univariate models, the secondary attack rate (SAR) was significantly higher when living in a household with two or more primary cases (incidence rate ratio (IRR) = 2.1; 95% confidence interval (CI) 1.37-3.29), more than one primary case with vomiting (IRR = 1.9; CI 1.11-3.37), and at least one primary case with diarrhoea (IRR = 3.0; CI 1.46-6.01). After controlling for other risk factors in the multivariate models, the SAR was significantly higher among those living in a household with two or more primary cases (adjusted IRR = 2.0; CI 1.17-3.47) and at least one primary case with diarrhoea (adjusted IRR = 2.8; CI 1.35-5.93). These findings underscore the importance of maintaining proper hygiene and isolating ill household members to prevent norovirus transmission in the household. |
Combating Enhanced intracellular survival (Eis)-mediated kanamycin resistance of Mycobacterium tuberculosis by novel pyrrolo[1,5-a]pyrazine-based Eis inhibitors
Garzan A , Willby MJ , Ngo HX , Gajadeera CS , Green KD , Holbrook SY , Hou C , Posey JE , Tsodikov OV , Garneau-Tsodikova S . ACS Infect Dis 2017 3 (4) 302-309 Tuberculosis (TB) remains one of the leading causes of mortality worldwide. Hence, the identification of highly effective antitubercular drugs with novel modes of action is crucial. In this paper, we report the discovery and development of pyrrolo[1,5-a]pyrazine-based analogues as highly potent inhibitors of the Mycobacterium tuberculosis (Mtb) acetyltransferase enhanced intracellular survival (Eis), whose up-regulation causes clinically observed resistance to the aminoglycoside (AG) antibiotic kanamycin A (KAN). We performed a structure-activity relationship (SAR) study to optimize these compounds as potent Eis inhibitors both against purified enzyme and in mycobacterial cells. A crystal structure of Eis in complex with one of the most potent inhibitors reveals that the compound is bound to Eis in the AG binding pocket, serving as the structural basis for the SAR. These Eis inhibitors have no observed cytotoxicity to mammalian cells and are promising leads for the development of innovative AG adjuvant therapies against drug-resistant TB. |
Establishing seasonal and alert influenza thresholds in Cambodia using the WHO method: implications for effective utilization of influenza surveillance in the tropics and subtropics
Ly S , Arashiro T , Ieng V , Tsuyuoka R , Parry A , Horwood P , Heng S , Hamid S , Vandemaele K , Chin S , Sar B , Arima Y . Western Pac Surveill Response J 2017 8 (1) 22-32 OBJECTIVE: To establish seasonal and alert thresholds and transmission intensity categories for influenza to provide timely triggers for preventive measures or upscaling control measures in Cambodia. METHODS: Using Cambodia's influenza-like illness (ILI) and laboratory-confirmed influenza surveillance data from 2009 to 2015, three parameters were assessed to monitor influenza activity: the proportion of ILI patients among all outpatients, proportion of ILI samples positive for influenza and the product of the two. With these parameters, four threshold levels (seasonal, moderate, high and alert) were established and transmission intensity was categorized based on a World Health Organization alignment method. Parameters were compared against their respective thresholds. RESULTS: Distinct seasonality was observed using the two parameters that incorporated laboratory data. Thresholds established using the composite parameter, combining syndromic and laboratory data, had the least number of false alarms in declaring season onset and were most useful in monitoring intensity. Unlike in temperate regions, the syndromic parameter was less useful in monitoring influenza activity or for setting thresholds. CONCLUSION: Influenza thresholds based on appropriate parameters have the potential to provide timely triggers for public health measures in a tropical country where monitoring and assessing influenza activity has been challenging. Based on these findings, the Ministry of Health plans to raise general awareness regarding influenza among the medical community and the general public. Our findings have important implications for countries in the tropics/subtropics and in resource-limited settings, and categorized transmission intensity can be used to assess severity of potential pandemic influenza as well as seasonal influenza. |
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. |
Isolation of H5N6, H7N9 and H9N2 avian influenza A viruses from air sampled at live poultry markets in China, 2014 and 2015
Zhou J , Wu J , Zeng X , Huang G , Zou L , Song Y , Gopinath D , Zhang X , Kang M , Lin J , Cowling BJ , Lindsley WG , Ke C , Peiris JS , Yen HL . Euro Surveill 2016 21 (35) Zoonotic infections by avian influenza viruses occur at the human-poultry interface, but the modes of transmission have not been fully investigated. We assessed the potential for airborne and fomite transmission at live poultry markets in Guangzhou city and in Hong Kong Special Administrative Region (SAR), China, during 2014 and 2015. Viral genome and infectious avian influenza A viruses of H5N6, H7N9, and H9N2 subtypes were detected predominantly from particles larger or equal to 1 mum in diameter in the air sampled with cyclone-based bioaerosol samplers at the live poultry markets in Guangzhou. Influenza A(H9N2) viruses were ubiquitously isolated every month during the study period from air and environmental swabs, and different lineages of H9N2 virus were isolated from markets where chickens and minor land-based poultry were sold. The use of de-feathering devices increased the quantity of virus-laden airborne particles while market closure reduced the amount of such particles. The results highlight the possibility of airborne transmission of avian influenza viruses among poultry or from poultry to humans within such settings. This may explain epidemiological observations in which some patients with H7N9 infection reported being in markets but no direct contact with live poultry or poultry stalls. |
Gang membership and marijuana use among African American female adolescents in North Carolina
Wechsberg WM , Doherty IA , Browne FA , Kline TL , Carry MG , Raiford JL , Herbst JH . Subst Abuse Rehabil 2015 6 141-150 The southeastern US sustains the highest high school dropout rates, and gangs persist in underserved communities. African American female adolescents who drop out of school and are gang members are at substantial risk of exposure to severe violence, physical abuse, and sexual exploitation. In this study of 237 female African American adolescents 16-19 years of age from North Carolina who dropped out or considered dropping out, 11% were current or past gang members. Adolescents who reported gang membership began smoking marijuana at a mean age of 13, whereas those who reported no gang membership began at a mean age of 15 years (P<0.001). The mean ages of first alcohol use were 14 years and 15 years for gang members and non-gang members, respectively (P=0.04). Problem alcohol use was high in both groups: 40% and 65% for non-gang and gang members, respectively (P=0.02). Controlling for frequent marijuana use and problem alcohol use, adolescents who reported gang membership were more likely than non-gang members to experience sexual abuse (odds ratio [OR] =2.60, 95% confidence interval [CI] [1.06, 6.40]), experience physical abuse (OR =7.33, 95% CI [2.90, 18.5]), report emotional abuse from their main partner (OR =3.55, 95% CI [1.44, 8.72]), run away from home (OR =4.65, 95% CI [1.90, 11.4]), get arrested (OR =2.61, 95% CI [1.05, 6.47]), and report violence in their neighborhood including murder (OR =3.27, 95% CI [1.35, 7.96]) and fights with weapons (OR =3.06, 95% CI [1.15, 8.11]). Gang members were less likely to receive emotional support (OR =0.89, 95% CI [0.81, 0.97]). These findings reinforce the urgent need to reach young African American women in disadvantaged communities affiliated with gangs to address the complexity of context and interconnected risk behaviors. |
Natural co-infection of influenza A/H3N2 and A/H1N1pdm09 viruses resulting in a reassortant A/H3N2 virus.
Rith S , Chin S , Sar B , Y P , Horm SV , Ly S , Buchy P , Dussart P , Horwood PF . J Clin Virol 2015 73 108-111 BACKGROUND: Despite annual co-circulation of different subtypes of seasonal influenza, co-infections between different viruses are rarely detected. These co-infections can result in the emergence of reassortant progeny. STUDY DESIGN: We document the detection of an influenza co-infection, between influenza A/H3N2 with A/H1N1pdm09 viruses, which occurred in a 3 year old male in Cambodia during April 2014. Both viruses were detected in the patient at relatively high viral loads (as determined by real-time RT-PCR CT values), which is unusual for influenza co-infections. As reassortment can occur between co-infected influenza A strains we isolated plaque purified clonal viral populations from the clinical material of the patient infected with A/H3N2 and A/H1N1pdm09. RESULTS: Complete genome sequences were completed for 7 clonal viruses to determine if any reassorted viruses were generated during the influenza virus co-infection. Although most of the viral sequences were consistent with wild-type A/H3N2 or A/H1N1pdm09, one reassortant A/H3N2 virus was isolated which contained an A/H1N1pdm09 NS1 gene fragment. The reassortant virus was viable and able to infect cells, as judged by successful passage in MDCK cells, achieving a TCID50 of 104/ml at passage number two. There is no evidence that the reassortant virus was transmitted further. The co-infection occurred during a period when co-circulation of A/H3N2 and A/H1N1pdm09 was detected in Cambodia. CONCLUSIONS: It is unclear how often influenza co-infections occur, but laboratories should consider influenza co-infections during routine surveillance activities. |
Case-ascertained study of household transmission of seasonal influenza - South Africa, 2013
Iyengar P , von Mollendorf C , Tempia S , Moerdyk A , Valley-Omar Z , Hellferscee O , Martinson N , Chhagan M , McMorrow M , Gambhir M , Cauchemez S , Variava E , Masonoke K , Cohen AL , Cohen C . J Infect 2015 71 (5) 578-86 OBJECTIVES: The household is important in influenza transmission due to intensity of contact. Previous studies reported secondary attack rates (SAR) of 4-10% for laboratory-confirmed influenza in the household. Few have been conducted in middle-income countries. METHODS: We performed a case-ascertained household transmission study during May-October 2013. Index cases were patients with influenza like illness(cough and self-reported or measured fever (≥38 degrees C)) with onset in the last 3 days and no sick household contacts, at clinics in South Africa. Household contacts of index cases with laboratory-confirmed influenza were followed for 12 days. RESULTS: Thirty index cases in 30 households and 107/110 (97%) eligible household contacts were enrolled. Assuming those not enrolled were influenza negative, 21/110 household contacts had laboratory-confirmed influenza (SAR 19%); the mean serial interval was 2.1 days (SD = 0.35, range 2-3 days). Most (62/82; 76%) household contacts who completed the risk factor questionnaire never avoided contact and 43/82 (52%) continued to share a bed with the index case after illness onset. CONCLUSION: SAR for laboratory-confirmed influenza in South Africa was higher than previously reported SARs. Household contacts did not report changing behaviors to prevent transmission. These results can be used to understand and predict influenza transmission in similar middle-income settings. |
Mapping influenza transmission in the ferret model to transmission in humans
Buhnerkempe MG , Gostic K , Park M , Ahsan P , Belser JA , Lloyd-Smith JO . Elife 2015 4 The controversy surrounding 'gain-of-function' experiments on high-consequence avian influenza viruses has highlighted the role of ferret transmission experiments in studying the transmission potential of novel influenza strains. However, the mapping between influenza transmission in ferrets and in humans is unsubstantiated. We address this gap by compiling and analyzing 240 estimates of influenza transmission in ferrets and humans. We demonstrate that estimates of ferret secondary attack rate (SAR) explain 66% of the variation in human SAR estimates at the subtype level. Further analysis shows that ferret transmission experiments have potential to identify influenza viruses of concern for epidemic spread in humans, though small sample sizes and biological uncertainties prevent definitive classification of human transmissibility. Thus, ferret transmission experiments provide valid predictions of pandemic potential of novel influenza strains, though results should continue to be corroborated by targeted virological and epidemiological research. |
Impact of intensive handwashing promotion on secondary household influenza-like illness in rural Bangladesh: findings from a randomized controlled trial
Ram PK , DiVita MA , Khatun EJannat K , Islam M , Krytus K , Cercone E , Sohel BM , Ahmed M , Rahman AM , Rahman M , Yu J , Brooks WA , Azziz-Baumgartner E , Fry AM , Luby SP . PLoS One 2015 10 (6) e0125200 RATIONALE: There is little evidence for the efficacy of handwashing for prevention of influenza transmission in resource-poor settings. We tested the impact of intensive handwashing promotion on household transmission of influenza-like illness and influenza in rural Bangladesh. METHODS: In 2009-10, we identified index case-patients with influenza-like illness (fever with cough or sore throat) who were the only symptomatic person in their household. Household compounds of index case-patients were randomized to control or intervention (soap and daily handwashing promotion). We conducted daily surveillance and collected oropharyngeal specimens. Secondary attack ratios (SAR) were calculated for influenza and ILI in each arm. Among controls, we investigated individual risk factors for ILI among household contacts of index case-patients. RESULTS: Among 377 index case-patients, the mean number of days between fever onset and study enrollment was 2.1 (SD 1.7) among the 184 controls and 2.6 (SD 2.9) among 193 intervention case-patients. Influenza infection was confirmed in 20% of controls and 12% of intervention index case-patients. The SAR for influenza-like illness among household contacts was 9.5% among intervention (158/1661) and 7.7% among control households (115/1498) (SAR ratio 1.24, 95% CI 0.92-1.65). The SAR ratio for influenza was 2.40 (95% CI 0.68-8.47). In the control arm, susceptible contacts <2 years old (RRadj 5.51, 95% CI 3.43-8.85), those living with an index case-patient enrolled ≤24 hours after symptom onset (RRadj 1.91, 95% CI 1.18-3.10), and those who reported multiple daily interactions with the index case-patient (RRadj 1.94, 95% CI 1.71-3.26) were at increased risk of influenza-like illness. DISCUSSION: Handwashing promotion initiated after illness onset in a household member did not protect against influenza-like illness or influenza. Behavior may not have changed rapidly enough to curb transmission between household members. A reactive approach to reduce household influenza transmission through handwashing promotion may be ineffective in the context of rural Bangladesh. TRIAL REGISTRATION: ClinicalTrials.gov NCT00880659. |
Detecting spread of avian influenza A(H7N9) virus beyond China
Millman AJ , Havers F , Iuliano AD , Davis CT , Sar B , Sovann L , Chin S , Corwin AL , Vongphrachanh P , Douangngeun B , Lindblade KA , Chittaganpitch M , Kaewthong V , Kile JC , Nguyen HT , Pham DV , Donis RO , Widdowson MA . Emerg Infect Dis 2015 21 (5) 741-9 During February 2013-March 2015, a total of 602 human cases of low pathogenic avian influenza A(H7N9) were reported; no autochthonous cases were reported outside mainland China. In contrast, since highly pathogenic avian influenza A(H5N1) reemerged during 2003 in China, 784 human cases in 16 countries and poultry outbreaks in 53 countries have been reported. Whether the absence of reported A(H7N9) outside mainland China represents lack of spread or lack of detection remains unclear. We compared epidemiologic and virologic features of A(H5N1) and A(H7N9) and used human and animal influenza surveillance data collected during April 2013-May 2014 from 4 Southeast Asia countries to assess the likelihood that A(H7N9) would have gone undetected during 2014. Surveillance in Vietnam and Cambodia detected human A(H5N1) cases; no A(H7N9) cases were detected in humans or poultry in Southeast Asia. Although we cannot rule out the possible spread of A(H7N9), substantial spread causing severe disease in humans is unlikely. |
Application of pharmacokinetic modelling for 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure assessment
Ruiz P , Aylward LL , Mumtaz M . SAR QSAR Environ Res 2014 25 (11) 873-90 Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and mono- and non-ortho polychlorinated biphenyls (dioxin-like PCBs) are identified as a family or group of organic compounds known as 'dioxins' or dioxin-like chemicals (DLCs). The most toxic member of this group is 2,3,7,8-tetrachlorodibenzo-(p)-dioxin (TCDD). Historically, DLCs have caused a variety of negative human health effects, but a disfiguring skin condition known as chloracne is the only health effect reported consistently. As part of translational research to make computerized models accessible to health risk assessors, the Concentration- and Age-Dependent Model (CADM) for TCDD was recoded in the Berkeley Madonna simulation language. The US Agency for Toxic Substances and Disease Registry's computational toxicology laboratory used the recoded model to predict TCDD tissue concentrations at different exposure levels. The model simulations successfully reproduced the National Health and Nutrition Examination Survey (NHANES) 2001-2002 TCDD data in age groups from 6 to 60 years and older, as well as in other human datasets. The model also enabled the estimation of lipid-normalized serum TCDD concentrations in breastfed infants. The model performed best for low background exposures over time compared with a high acute poisoning case that could due to the large dose and associated liver toxicity. Hence, this model may be useful for interpreting human biomonitoring data as a part of an overall DLC risk assessment. |
Epidemiological and virological characteristics of influenza viruses circulating in Cambodia from 2009 to 2011.
Horm SV , Mardy S , Rith S , Ly S , Heng S , Vong S , Kitsutani P , Ieng V , Tarantola A , Ly S , Sar B , Chea N , Sokhal B , Barr I , Kelso A , Horwood PF , Timmermans A , Hurt A , Lon C , Saunders D , Ung SA , Asgari N , Roces MC , Touch S , Komadina N , Buchy P . PLoS One 2014 9 (10) e110713 BACKGROUND: The Cambodian National Influenza Center (NIC) monitored and characterized circulating influenza strains from 2009 to 2011. METHODOLOGY/PRINCIPAL FINDINGS: Sentinel and study sites collected nasopharyngeal specimens for diagnostic detection, virus isolation, antigenic characterization, sequencing and antiviral susceptibility analysis from patients who fulfilled case definitions for influenza-like illness, acute lower respiratory infections and event-based surveillance. Each year in Cambodia, influenza viruses were detected mainly from June to November, during the rainy season. Antigenic analysis show that A/H1N1pdm09 isolates belonged to the A/California/7/2009-like group. Circulating A/H3N2 strains were A/Brisbane/10/2007-like in 2009 before drifting to A/Perth/16/2009-like in 2010 and 2011. The Cambodian influenza B isolates from 2009 to 2011 all belonged to the B/Victoria lineage represented by the vaccine strains B/Brisbane/60/2008 and B/Malaysia/2506/2004. Sequences of the M2 gene obtained from representative 2009-2011 A/H3N2 and A/H1N1pdm09 strains all contained the S31N mutation associated with adamantanes resistance except for one A/H1N1pdm09 strain isolated in 2011 that lacked this mutation. No reduction in the susceptibility to neuraminidase inhibitors was observed among the influenza viruses circulating from 2009 to 2011. Phylogenetic analysis revealed that A/H3N2 strains clustered each year to a distinct group while most A/H1N1pdm09 isolates belonged to the S203T clade. CONCLUSIONS/SIGNIFICANCE: In Cambodia, from 2009 to 2011, influenza activity occurred throughout the year with peak seasonality during the rainy season from June to November. Seasonal influenza epidemics were due to multiple genetically distinct viruses, even though all of the isolates were antigenically similar to the reference vaccine strains. The drug susceptibility profile of Cambodian influenza strains revealed that neuraminidase inhibitors would be the drug of choice for influenza treatment and chemoprophylaxis in Cambodia, as adamantanes are no longer expected to be effective. |
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