Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-30 (of 43 Records) |
Query Trace: Balish A[original query] |
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Seroprevalence of high incidence congenital infections among pregnant women in Coatepeque, Guatemala and surrounding areas, 2017-2018
Hicks VJ , Sánchez C , López MR , Gottschlich A , Grajeda LM , Balish A , Gómez A , Nuñez N , Juárez J , López B , Freitas-Ning M , Cordón-Rosales C , Sagastume M , McCracken JP , Espinosa-Bode A , Cadena L , Lo TQ . PLoS Negl Trop Dis 2023 17 (4) e0011248 Maternal infections during pregnancy can potentially cause birth defects and severe adverse effects in infants. From 2017 to 2018, we investigated the seroprevalence of five antibodies among 436 mother-infant pairs enrolled in a pregnancy cohort study in Coatepeque, Guatemala. Upon enrollment (< 20 weeks gestational age) and shortly after delivery, we measured the prevalence of IgG and IgM antibodies against Toxoplasma gondii (T. gondii), rubella, and cytomegalovirus (CMV) in mothers and newborns and used rapid tests to detect HIV and syphilis (Treponema pallidum) in mothers. The mean cohort age was 24.5 years. Maternal T. gondii IgM and IgG seropositivity was 1.9% and 69.7%, respectively. No women were positive for HIV, syphilis, or rubella IgM. Maternal rubella IgG seropositivity was 80.8% and significantly increased with age. Maternal CMV IgM and IgG seropositivity were 2.3% and 99.5%, respectively. Of the 323 women tested at both timepoints, IgM reactivation occurred in one woman for T. gondii infection and in eight for CMV. No newborn was seropositive for CMV IgM or rubella IgM. One newborn was seropositive for T. gondii IgM. Congenital T. gondii and CMV infections are important public health issues for pregnant women, newborns, and healthcare providers in Coatepeque and Guatemala. |
Incorporating COVID-19 into acute febrile illness surveillance systems, Belize, Kenya, Ethiopia, Peru, and Liberia, 2020-2021
Shih DC , Silver R , Henao OL , Alemu A , Audi A , Bigogo G , Colston JM , Edu-Quansah EP , Erickson TA , Gashu A , Gbelee GB Jr , Gunter SM , Kosek MN , Logan GG , Mackey JM , Maliga A , Manzanero R , Morazan G , Morey F , Munoz FM , Murray KO , Nelson TV , Olortegui MP , Yori PP , Ronca SE , Schiaffino F , Tayachew A , Tedasse M , Wossen M , Allen DR , Angra P , Balish A , Farron M , Guerra M , Herman-Roloff A , Hicks VJ , Hunsperger E , Kazazian L , Mikoleit M , Munyua P , Munywoki PK , Namwase AS , Onyango CO , Park M , Peruski LF , Sugerman DE , Gutierrez EZ , Cohen AL . Emerg Infect Dis 2022 28 (13) S34-s41 Existing acute febrile illness (AFI) surveillance systems can be leveraged to identify and characterize emerging pathogens, such as SARS-CoV-2, which causes COVID-19. The US Centers for Disease Control and Prevention collaborated with ministries of health and implementing partners in Belize, Ethiopia, Kenya, Liberia, and Peru to adapt AFI surveillance systems to generate COVID-19 response information. Staff at sentinel sites collected epidemiologic data from persons meeting AFI criteria and specimens for SARS-CoV-2 testing. A total of 5,501 patients with AFI were enrolled during March 2020-October 2021; >69% underwent SARS-CoV-2 testing. Percentage positivity for SARS-CoV-2 ranged from 4% (87/2,151, Kenya) to 19% (22/115, Ethiopia). We show SARS-CoV-2 testing was successfully integrated into AFI surveillance in 5 low- to middle-income countries to detect COVID-19 within AFI care-seeking populations. AFI surveillance systems can be used to build capacity to detect and respond to both emerging and endemic infectious disease threats. |
Strengthening laboratory biosafety in Liberia during the COVID-19 pandemic: Experience from the Global Laboratory Leadership Programme.
Malik S , Taweh FM , Freeman M , Dogba JB , Gwesa GO , Tokpah M , Gbondin PP , Kohar TH , Hena JY , MaCauley JA , Pierson A , Rayfield MA , Peruski LF , Albetkova A , Balish A . One Health 2022 15 100442 BACKGROUND: The Global Laboratory Leadership Programme (GLLP) has biosafety and biosecurity as one of its core competencies and advocates for a One Health approach involving all relevant sectors across the human-animal-environment interface to empower national laboratory systems and strengthen health security. Decentralization of SARS-CoV-2 testing in Liberia coupled with an increase in the number of COVID-19 infections among laboratory professionals raised biosafety concerns. In response, a set of trainings on laboratory biosafety was launched for lab personnel across the country under the framework of the GLLP. The goal was to deliver a comprehensive package for laboratory biosafety in the context of SARS-CoV-2 through active learning. METHODS: Three one-day workshops were conducted between September and October 2020, training personnel from human, animal and environmental laboratories through a One Health approach. Concepts critical to laboratory biosafety were delivered in an interactive engagement format to ensure effective learning and retention of concepts. Pre- and post-training assessments were performed, and a paired t-test was used to assess knowledge gain. RESULTS: Of the 67 participants, 64 were from the human health sector, one from veterinary sector and two from environmental health sector. The average pre-test score was 41%. The main gaps identified were failure to acknowledge surgical antisepsis as a form of hand hygiene and recognition of PPE as the best risk control measure. The average post-test score was 75.5%. The mean difference of pre-test and post-test scores was statistically significant (p-value <0.001). Participants indicated satisfaction with the workshop content, mode of delivery and trainers' proficiency. CONCLUSIONS: The workshops were impactful as evidenced by significant improvement (34.5%) in the post-test scores and positive participant feedback. Repeated refresher trainings are vital to addressing the gaps, ensuring compliance, and promoting biosafety culture. GLLP's approach to cultivating multisectoral national laboratory leaders ready to take responsibility and ownership for capacity building provides a sustainable solution for attaining strong national laboratory systems better prepared for health emergencies and pandemics like COVID-19. |
Changes in the receptor-binding properties of H3N2 viruses during long-term circulation in humans
Gambaryan AS , Balish A , Klimov AI , Tuzikov AB , Chinarev AA , Pazynina GV , Bovin NV . Biochemistry (Mosc) 2019 84 (10) 1177-1185 It was previously shown that hemagglutinin residues Thrl55, Glul58, and Ser228 are crucial for the recognition of Neu5Gc. In this study, we demonstrated that the ability to bind the Neu5Gc-terminated receptor is related to the amino acid 145: viruses of years 1972–1999 with Lysl45bindto the receptor, whereas viruses with Asnl 45 do not. Sporadic appearance and disappearance of the ability to bind Neu5Gc oligosaccharides and the absence of Neu5Gc in the composition of human glycoconjugates indicate the non-adaptive nature of this ability. It was previously shown that unlike H1N1 viruses, H3N2 viruses of years 1968–1989 did not distinguish between Neu5Acα2-6Galβ1-4Glc (6′SL) and Neu5Acα2-6Galβ1-4GlcNAc (6′SLN). H3N2 viruses isolated after 1993 have acquired the ability to distinguish between 6’SL and 6′SLN, similarly to H1N1 viruses. We found that the affinity for 6′SLN has gradually increased from 1992 to 2003. After 2003, the viruses lost the ability to bind a number of sialosides, including 6′SL, that were good receptors for earlier H3N2 viruses, and retained high affinity for 6′SLN only, which correlated with the acquisition of new glycosylation sites at positions 122, 133, and 144, as well as Glul90Asp and Gly225Asp substitutions, in hemagglutinin. These substitutions are also responsible for the receptor-binding phenotype of human H1N1 viruses. We conclude that the convergent evolution of the receptor specificity of the H1N1 and H3N2 viruses indicates that 6’SLN is the optimal natural human receptor for influenza viruses. |
Avian influenza surveillance in domestic waterfowl and environment of live bird markets in Bangladesh, 2007-2012.
Khan SU , Gurley ES , Gerloff N , Rahman MZ , Simpson N , Rahman M , Haider N , Chowdhury S , Balish A , Zaman RU , Nasreen S , Chandra Das B , Azziz-Baumgartner E , Sturm-Ramirez K , Davis CT , Donis RO , Luby SP . Sci Rep 2018 8 (1) 9396 Avian influenza viruses, including highly pathogenic strains, pose severe economic, animal and public health concerns. We implemented live bird market surveillance in Bangladesh to identify the subtypes of avian influenza A viruses in domestic waterfowl and market environments. We collected waterfowl samples monthly from 4 rural sites from 2007 to 2012 and environmental samples from 4 rural and 16 urban sites from 2009 to 2012. Samples were tested through real-time RT-PCR, virus culture, and sequencing to detect and characterize avian influenza A viruses. Among 4,308 waterfowl tested, 191 (4.4%) were positive for avian influenza A virus, including 74 (1.9%) avian influenza A/H5 subtype. The majority (99%, n = 73) of the influenza A/H5-positive samples were from healthy appearing waterfowl. Multiple subtypes, including H1N1, H1N3, H3N2, H3N6, H3N8, H4N1, H4N2, H4N6, H5N1 (clades 2.2.2, 2.3.2.1a, 2.3.4.2), H5N2, H6N1, H7N9, H9N2, H11N2 and H11N3, H11N6 were detected in waterfowl and environmental samples. Environmental samples tested positive for influenza A viruses throughout the year. Avian influenza viruses, including H5N1 and H9N2 subtypes were also identified in backyard and small-scale raised poultry. Live bird markets could be high-risk sites for harboring the viruses and have the potential to infect naive birds and humans exposed to them. |
Antigenic characterization of highly pathogenic avian influenza A(H5N1) viruses with chicken and ferret antisera reveals clade-dependent variation in hemagglutination inhibition profiles
Thi Nguyen D , Shepard SS , Burke DF , Jones J , Thor S , Nguyen LV , Nguyen TD , Balish A , Hoang DN , To TL , Iqbal M , Wentworth DE , Spackman E , van Doorn HR , Davis CT , Bryant JE . Emerg Microbes Infect 2018 7 (1) 100 Highly pathogenic avian influenza (HPAI) A(H5N1) viruses pose a significant economic burden to the poultry industry worldwide and have pandemic potential. Poultry vaccination against HPAI A(H5N1) viruses has been an important component of HPAI control measures and has been performed in Vietnam since 2005. To systematically assess antigenic matching of current vaccines to circulating field variants, we produced a panel of chicken and ferret antisera raised against historical and contemporary Vietnamese reference viruses representing clade variants that were detected between 2001 and 2014. The antisera were used for hemagglutination inhibition (HI) assays to generate data sets for analysis by antigenic cartography, allowing for a direct comparison of results from chicken or ferret antisera. HI antigenic maps, developed with antisera from both hosts, revealed varying patterns of antigenic relationships and clustering of viruses that were dependent on the clade of viruses analyzed. Antigenic relationships between existing poultry vaccines and circulating field viruses were also aligned with in vivo protection profiles determined by previously reported vaccine challenge studies. Our results establish the feasibility and utility of HPAI A(H5N1) antigenic characterization using chicken antisera and support further experimental and modeling studies to investigate quantitative relationships between genetic variation, antigenic drift and correlates of poultry vaccine protection in vivo. |
Highly Pathogenic Avian Influenza A(H5N1) Viruses at the Animal-Human Interface in Vietnam, 2003-2010.
Creanga A , Hang NLK , Cuong VD , Nguyen HT , Phuong HVM , Thanh LT , Thach NC , Hien PT , Tung N , Jang Y , Balish A , Dang NH , Duong MT , Huong NT , Hoa DN , Tho ND , Klimov A , Kapella BK , Gubareva L , Kile JC , Hien NT , Mai LQ , Davis CT . J Infect Dis 2017 216 S529-s538 Mutation and reassortment of highly pathogenic avian influenza A(H5N1) viruses at the animal-human interface remain a major concern for emergence of viruses with pandemic potential. To understand the relationship of H5N1 viruses circulating in poultry and those isolated from humans, comprehensive phylogenetic and molecular analyses of viruses collected from both hosts in Vietnam between 2003 and 2010 were performed. We examined the temporal and spatial distribution of human cases relative to H5N1 poultry outbreaks and characterized the genetic lineages and amino acid substitutions in each gene segment identified in humans relative to closely related viruses from avian hosts. Six hemagglutinin clades and 8 genotypes were identified in humans, all of which were initially identified in poultry. Several amino acid mutations throughout the genomes of viruses isolated from humans were identified, indicating the potential for poultry viruses infecting humans to rapidly acquire molecular markers associated with mammalian adaptation and antiviral resistance. |
Genetically Diverse Low Pathogenicity Avian Influenza A Virus Subtypes Co-Circulate among Poultry in Bangladesh.
Gerloff NA , Khan SU , Zanders N , Balish A , Haider N , Islam A , Chowdhury S , Rahman MZ , Haque A , Hosseini P , Gurley ES , Luby SP , Wentworth DE , Donis RO , Sturm-Ramirez K , Davis CT . PLoS One 2016 11 (3) e0152131 Influenza virus surveillance, poultry outbreak investigations and genomic sequencing were assessed to understand the ecology and evolution of low pathogenicity avian influenza (LPAI) A viruses in Bangladesh from 2007 to 2013. We analyzed 506 avian specimens collected from poultry in live bird markets and backyard flocks to identify influenza A viruses. Virus isolation-positive specimens (n = 50) were subtyped and their coding-complete genomes were sequenced. The most frequently identified subtypes among LPAI isolates were H9N2, H11N3, H4N6, and H1N1. Less frequently detected subtypes included H1N3, H2N4, H3N2, H3N6, H3N8, H4N2, H5N2, H6N1, H6N7, and H7N9. Gene sequences were compared to publicly available sequences using phylogenetic inference approaches. Among the 14 subtypes identified, the majority of viral gene segments were most closely related to poultry or wild bird viruses commonly found in Southeast Asia, Europe, and/or northern Africa. LPAI subtypes were distributed over several geographic locations in Bangladesh, and surface and internal protein gene segments clustered phylogenetically with a diverse number of viral subtypes suggesting extensive reassortment among these LPAI viruses. H9N2 subtype viruses differed from other LPAI subtypes because genes from these viruses consistently clustered together, indicating this subtype is enzootic in Bangladesh. The H9N2 strains identified in Bangladesh were phylogenetically and antigenically related to previous human-derived H9N2 viruses detected in Bangladesh representing a potential source for human infection. In contrast, the circulating LPAI H5N2 and H7N9 viruses were both phylogenetically and antigenically unrelated to H5 viruses identified previously in humans in Bangladesh and H7N9 strains isolated from humans in China. In Bangladesh, domestic poultry sold in live bird markets carried a wide range of LPAI virus subtypes and a high diversity of genotypes. These findings, combined with the seven year timeframe of sampling, indicate a continuous circulation of these viruses in the country. |
Capacity building in national influenza laboratories - use of laboratory assessments to drive progress
Johnson LE , Muir-Paulik SA , Kennedy P , Lindstrom S , Balish A , Aden T , Moen AC . BMC Infect Dis 2015 15 (1) 501 BACKGROUND: Laboratory testing is a fundamental component of influenza surveillance for detecting novel strains with pandemic potential and informing biannual vaccine strain selection. The United States (U.S.) Centers for Disease Control and Prevention (CDC), under the auspices of its WHO Collaborating Center for Influenza, is one of the major public health agencies which provides support globally to build national capacity for influenza surveillance. Our main objective was to determine if laboratory assessments supported capacity building efforts for improved global influenza surveillance. METHODS: In 2010, 35 national influenza laboratories were assessed in 34 countries, using a standardized tool. Post-assessment, each laboratory received a report with a list of recommendations for improvement. Uptake of recommendations were reviewed 3.2 mean years after the initial assessments and categorized as complete, in-progress, no action or no update. This was a retrospective study; follow-up took place through routine project management rather than at a set time-point post-assessment. WHO data on National Influenza Centre (NIC) designation, External Quality Assessment Project (EQAP) participation and FluNet reporting was used to measure laboratory capacity longitudinally and independently of the assessments. All data was further stratified by World Bank country income category. RESULTS: At follow-up, 81 % of 614 recommendations were either complete (350) or in-progress (145) for 32 laboratories (91 % response rate). The number of countries reporting to FluNet and the number of specimens they reported annually increased between 2005, when they were first funded by CDC, and 2010, the assessment year (p < 0.01). Improvements were also seen in EQAP participation and NIC designation over time and more so for low and lower-middle income countries. CONCLUSIONS: Assessments using a standardized tool have been beneficial to improving laboratory-based influenza surveillance. Specific recommendations helped countries identify and prioritize areas for improvement. Data from assessments helped CDC focus its technical assistance by country and region. Low and lower-middle income countries made greater improvements in their laboratories compared with upper-middle income countries. Future research could include an analysis of annual funding and technical assistance by country. Our approach serves as an example for capacity building for other diseases. |
Generation and Characterization of Live Attenuated Influenza A(H7N9) Candidate Vaccine Virus Based on Russian Donor of Attenuation.
Shcherbik S , Pearce N , Balish A , Jones J , Thor S , Davis CT , Pearce M , Tumpey T , Cureton D , Chen LM , Villanueva J , Bousse TL . PLoS One 2015 10 (9) e0138951 BACKGROUND: Avian influenza A (H7N9) virus has emerged recently and continues to cause severe disease with a high mortality rate in humans prompting the development of candidate vaccine viruses. Live attenuated influenza vaccines (LAIV) are 6:2 reassortant viruses containing the HA and NA gene segments from wild type influenza viruses to induce protective immune responses and the six internal genes from Master Donor Viruses (MDV) to provide temperature sensitive, cold-adapted and attenuated phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: LAIV candidate A/Anhui/1/2013(H7N9)-CDC-LV7A (abbreviated as CDC-LV7A), based on the Russian MDV, A/Leningrad/134/17/57 (H2N2), was generated by classical reassortment in eggs and retained MDV temperature-sensitive and cold-adapted phenotypes. CDC-LV7A had two amino acid substitutions N123D and N149D (H7 numbering) in HA and one substitution T10I in NA. To evaluate the role of these mutations on the replication capacity of the reassortants in eggs, the recombinant viruses A(H7N9)RG-LV1 and A(H7N9)RG-LV2 were generated by reverse genetics. These changes did not alter virus antigenicity as ferret antiserum to CDC-LV7A vaccine candidate inhibited hemagglutination by homologous A(H7N9) virus efficiently. Safety studies in ferrets confirmed that CDC-LV7A was attenuated compared to wild-type A/Anhui/1/2013. In addition, the genetic stability of this vaccine candidate was examined in eggs and ferrets by monitoring sequence changes acquired during virus replication in the two host models. No changes in the viral genome were detected after five passages in eggs. However, after ten passages additional mutations were detected in the HA gene. The vaccine candidate was shown to be stable in the ferret model; post-vaccination sequence data analysis showed no changes in viruses collected in nasal washes present at day 5 or day 7. CONCLUSIONS/SIGNIFICANCE: Our data indicate that the A/Anhui/1/2013(H7N9)-CDC-LV7A reassortant virus is a safe and genetically stable candidate vaccine virus that is now available for distribution by WHO to vaccine manufacturers. |
Detection and Characterization of Clade 1 Reassortant H5N1 Viruses Isolated from Human Cases in Vietnam during 2013.
Thor SW , Nguyen H , Balish A , Hoang AN , Gustin KM , Nhung PT , Jones J , Thu NN , Davis W , Ngoc TN , Jang Y , Sleeman K , Villanueva J , Kile J , Gubareva LV , Lindstrom S , Tumpey TM , Davis CT , Long NT . PLoS One 2015 10 (8) e0133867 Highly pathogenic avian influenza (HPAI) H5N1 is endemic in Vietnamese poultry and has caused sporadic human infection in Vietnam since 2003. Human infections with HPAI H5N1 are of concern due to a high mortality rate and the potential for the emergence of pandemic viruses with sustained human-to-human transmission. Viruses isolated from humans in southern Vietnam have been classified as clade 1 with a single genome constellation (VN3) since their earliest detection in 2003. This is consistent with detection of this clade/genotype in poultry viruses endemic to the Mekong River Delta and surrounding regions. Comparison of H5N1 viruses detected in humans from southern Vietnamese provinces during 2012 and 2013 revealed the emergence of a 2013 reassortant virus with clade 1.1.2 hemagglutinin (HA) and neuraminidase (NA) surface protein genes but internal genes derived from clade 2.3.2.1a viruses (A/Hubei/1/2010-like; VN12). Closer analysis revealed mutations in multiple genes of this novel genotype (referred to as VN49) previously associated with increased virulence in animal models and other markers of adaptation to mammalian hosts. Despite the changes identified between the 2012 and 2013 genotypes analyzed, their virulence in a ferret model was similar. Antigenically, the 2013 viruses were less cross-reactive with ferret antiserum produced to the clade 1 progenitor virus, A/Vietnam/1203/2004, but reacted with antiserum produced against a new clade 1.1.2 WHO candidate vaccine virus (A/Cambodia/W0526301/2012) with comparable hemagglutination inhibition titers as the homologous antigen. Together, these results indicate changes to both surface and internal protein genes of H5N1 viruses circulating in southern Vietnam compared to 2012 and earlier viruses. |
Development of influenza A(H7N9) candidate vaccine viruses with improved hemagglutinin antigen yield in eggs
Ridenour C , Johnson A , Winne E , Hossain J , Mateu-Petit G , Balish A , Santana W , Kim T , Davis C , Cox NJ , Barr JR , Donis RO , Villanueva J , Williams TL , Chen LM . Influenza Other Respir Viruses 2015 9 (5) 263-70 BACKGROUND: The emergence of avian influenza A(H7N9) virus in poultry causing zoonotic human infections was reported on March 31, 2013. Development of A(H7N9) candidate vaccine viruses (CVV) for pandemic preparedness purposes was initiated without delay. Candidate vaccine viruses were derived by reverse genetics using the internal genes of A/Puerto/Rico/8/34 (PR8). The resulting A(H7N9) CVVs needed improvement because they had titers and antigen yields that were suboptimal for vaccine manufacturing in eggs, especially in a pandemic situation. METHODS: Two CVVs derived by reverse genetics were serially passaged in embryonated eggs to improve the hemagglutinin (HA) antigen yield. The total viral protein and HA antigen yields of six egg-passaged CVVs were determined by the BCA assay and isotope dilution mass spectrometry (IDMS) analysis, respectively. CVVs were antigenically characterized by hemagglutination inhibition (HI) assays with ferret antisera. RESULTS: Improvement of total viral protein yield was observed for the six egg-passaged CVVs; HA quantification by IDMS indicated approximately a two-fold increase in yield of several egg-passaged viruses as compared to that of the parental CVV. Several different amino acid substitutions were identified in the HA of all viruses after serial passage; however HI tests indicated that the antigenic properties of two CVVs remained unchanged. CONCLUSIONS: If influenza A(H7N9) viruses were to acquire sustained human to human transmissibility, the improved HA yield of the egg-passaged CVVs generated in this study could expedite vaccine manufacturing for pandemic mitigation. |
Unusually high mortality in waterfowl caused by highly pathogenic avian influenza A(H5N1) in Bangladesh
Haider N , Sturm-Ramirez K , Khan SU , Rahman MZ , Sarkar S , Poh MK , Shivaprasad HL , Kalam MA , Paul SK , Karmakar PC , Balish A , Chakraborty A , Mamun AA , Mikolon AB , Davis CT , Rahman M , Donis RO , Heffelfinger JD , Luby SP , Zeidner N . Transbound Emerg Dis 2015 64 (1) 144-156 Mortality in ducks and geese caused by highly pathogenic avian influenza A(H5N1) infection had not been previously identified in Bangladesh. In June-July 2011, we investigated mortality in ducks, geese and chickens with suspected H5N1 infection in a north-eastern district of the country to identify the aetiologic agent and extent of the outbreak and identify possible associated human infections. We surveyed households and farms with affected poultry flocks in six villages in Netrokona district and collected cloacal and oropharyngeal swabs from sick birds and tissue samples from dead poultry. We conducted a survey in three of these villages to identify suspected human influenza-like illness cases and collected nasopharyngeal and throat swabs. We tested all swabs by real-time RT-PCR, sequenced cultured viruses, and examined tissue samples by histopathology and immunohistochemistry to detect and characterize influenza virus infection. In the six villages, among the 240 surveyed households and 11 small-scale farms, 61% (1789/2930) of chickens, 47% (4816/10 184) of ducks and 73% (358/493) of geese died within 14 days preceding the investigation. Of 70 sick poultry swabbed, 80% (56/70) had detectable RNA for influenza A/H5, including 89% (49/55) of ducks, 40% (2/5) of geese and 50% (5/10) of chickens. We isolated virus from six of 25 samples; sequence analysis of the hemagglutinin and neuraminidase gene of these six isolates indicated clade 2.3.2.1a of H5N1 virus. Histopathological changes and immunohistochemistry staining of avian influenza viral antigens were recognized in the brain, pancreas and intestines of ducks and chickens. We identified ten human cases showing signs compatible with influenza-like illness; four were positive for influenza A/H3; however, none were positive for influenza A/H5. The recently introduced H5N1 clade 2.3.2.1a virus caused unusually high mortality in ducks and geese. Heightened surveillance in poultry is warranted to guide appropriate diagnostic testing and detect novel influenza strains. |
Identification of molecular markers associated with alteration of receptor-binding specificity in a novel genotype of highly pathogenic avian influenza A(H5N1) viruses detected in Cambodia in 2013.
Rith S , Davis CT , Duong V , Sar B , Horm SV , Chin S , Ly S , Laurent D , Richner B , Oboho I , Jang Y , Davis W , Thor S , Balish A , Iuliano AD , Sorn S , Holl D , Sok T , Seng H , Tarantola A , Tsuyuoka R , Parry A , Chea N , Allal L , Kitsutani P , Warren D , Prouty M , Horwood P , Widdowson MA , Lindstrom S , Villanueva J , Donis R , Cox N , Buchy P . J Virol 2014 88 (23) 13897-909 Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L). Discovery of quasispecies at position 222 (Q/L), in addition to absence of the mutations in poultry/environmental samples, suggested the mutations occurred during human infection and did not transmit further. |
Antiviral susceptibility of variant influenza A(H3N2)v viruses isolated in the United States from 2011 to 2013
Sleeman K , Mishin VP , Guo Z , Garten RJ , Balish A , Fry AM , Villanueva J , Stevens J , Gubareva LV . Antimicrob Agents Chemother 2014 58 (4) 2045-51 Since 2011, outbreaks caused by influenza A(H3N2) variant [A(H3N2)v] viruses have become a public health concern in the United States. The A(H3N2)v viruses share the A(H1N1)pdm09 M gene containing the marker of M2 blocker resistance, S31N, but do not contain any known molecular markers associated with resistance to neuraminidase (NA) inhibitors (NAIs). Using a fluorescent NA inhibition (NI) assay, the susceptibilities of recovered A(H3N2)v viruses (n = 168) to FDA-approved (oseltamivir and zanamivir) and other (peramivir, laninamivir, and A-315675) NAIs were assessed. All A(H3N2)v viruses tested, with the exception of a single virus strain, A/Ohio/88/2012, isolated from an untreated patient, were susceptible to the NAIs tested. The A/Ohio/88/2012 virus contained two rare substitutions, S245N and S247P, in the NA and demonstrated reduced inhibition by oseltamivir (31-fold) and zanamivir (66-fold) in the NI assay. Using recombinant NA (recNA) proteins, S247P was shown to be responsible for the observed altered NAI susceptibility, in addition to an approximately 60% reduction in NA enzymatic activity. The S247P substitution has not been previously reported as a molecular marker of reduced susceptibility to the NAIs. Using cell culture assays, the investigational antiviral drugs nitazoxanide, favipiravir, and fludase were shown to inhibit the replication of A(H3N2)v viruses, including the virus with the S247P substitution in the NA. This report demonstrates the importance of continuous monitoring of susceptibility of zoonotic influenza viruses to available and investigational antiviral drugs. |
Genetic characterization of clade 2.3.2.1 avian influenza A(H5N1) viruses, Indonesia, 2012.
Dharmayanti NL , Hartawan R , Wibawa H , Balish A , Donis R , Davis CT , Samaan G . Emerg Infect Dis 2014 20 (4) 677-80 After reports of unusually high mortality rates among ducks on farms in Java Island, Indonesia, in September 2012, influenza A(H5N1) viruses were detected and characterized. Sequence analyses revealed all genes clustered with contemporary clade 2.3.2.1 viruses, rather than enzootic clade 2.1.3 viruses, indicating the introduction of an exotic H5N1 clade into Indonesia. |
Investigating a crow die-off in January-February 2011 during the introduction of a new clade of highly pathogenic avian influenza virus H5N1 into Bangladesh
Khan SU , Berman L , Haider N , Gerloff N , Rahman MZ , Shu B , Rahman M , Dey TK , Davis TC , Das BC , Balish A , Islam A , Teifke JP , Zeidner N , Lindstrom S , Klimov A , Donis RO , Luby SP , Shivaprasad HL , Mikolon AB . Arch Virol 2014 159 (3) 509-18 We investigated unusual crow mortality in Bangladesh during January-February 2011 at two sites. Crows of two species, Corvus splendens and C. macrorhynchos, were found sick and dead during the outbreaks. In selected crow roosts, morbidity was ~1 % and mortality was ~4 % during the investigation. Highly pathogenic avian influenza virus H5N1 clade 2.3.2.1 was isolated from dead crows. All isolates were closely related to A/duck/India/02CA10/2011 (H5N1) with 99.8 % and A/crow/Bangladesh/11rs1984-15/2011 (H5N1) virus with 99 % nucleotide sequence identity in their HA genes. The phylogenetic cluster of Bangladesh viruses suggested a common ancestor with viruses found in poultry from India, Myanmar and Nepal. Histopathological changes and immunohistochemistry staining in brain, pancreas, liver, heart, kidney, bursa of Fabricius, rectum, and cloaca were consistent with influenza virus infection. Through our limited investigation in domesticated birds near the crow roosts, we did not identify any samples that tested positive for influenza virus A/H5N1. However, environmental samples collected from live-bird markets near an outbreak site during the month of the outbreaks tested very weakly positive for influenza virus A/H5N1 in clade 2.3.2.1-specific rRT-PCR. Continuation of surveillance in wild and domestic birds may identify evolution of new avian influenza virus and associated public-health risks. |
Multiple reassortment events among highly pathogenic avian influenza A(H5N1) viruses detected in Bangladesh.
Gerloff NA , Khan SU , Balish A , Shanta IS , Simpson N , Berman L , Haider N , Poh MK , Islam A , Gurley E , Hasnat MA , Dey T , Shu B , Emery S , Lindstrom S , Haque A , Klimov A , Villanueva J , Rahman M , Azziz-Baumgartner E , Ziaur Rahman M , Luby SP , Zeidner N , Donis RO , Sturm-Ramirez K , Davis CT . Virology 2014 450-451 297-307 In Bangladesh, little is known about the genomic composition and antigenicity of highly pathogenic avian influenza A(H5N1) viruses, their geographic distribution, temporal patterns, or gene flow within the avian host population. Forty highly pathogenic avian influenza A(H5N1) viruses isolated from humans and poultry in Bangladesh between 2008 and 2012 were analyzed by full genome sequencing and antigenic characterization. The analysis included viruses collected from avian hosts and environmental sampling in live bird markets, backyard poultry flocks, outbreak investigations in wild birds or poultry and from three human cases. Phylogenetic analysis indicated that the ancestors of these viruses reassorted (1) with other gene lineages of the same clade, (2) between different clades and (3) with low pathogenicity avian influenza A virus subtypes. Bayesian estimates of the time of most recent common ancestry, combined with geographic information, provided evidence of probable routes and timelines of virus spread into and out of Bangladesh. |
Outbreak of variant influenza A(H3N2) virus in the United States
Jhung MA , Epperson S , Biggerstaff M , Allen D , Balish A , Barnes N , Beaudoin A , Berman L , Bidol S , Blanton L , Blythe D , Brammer L , D'Mello T , Danila R , Davis W , de Fijter S , Diorio M , Durand LO , Emery S , Fowler B , Garten R , Grant Y , Greenbaum A , Gubareva L , Havers F , Haupt T , House J , Ibrahim S , Jiang V , Jain S , Jernigan D , Kazmierczak J , Klimov A , Lindstrom S , Longenberger A , Lucas P , Lynfield R , McMorrow M , Moll M , Morin C , Ostroff S , Page SL , Park SY , Peters S , Quinn C , Reed C , Richards S , Scheftel J , Simwale O , Shu B , Soyemi K , Stauffer J , Steffens C , Su S , Torso L , Uyeki TM , Vetter S , Villanueva J , Wong KK , Shaw M , Bresee JS , Cox N , Finelli L . Clin Infect Dis 2013 57 (12) 1703-12 BACKGROUND: Variant influenza virus infections are rare but may have pandemic potential if person-to-person transmission is efficient. We describe the epidemiology of a multistate outbreak of an influenza A(H3N2) variant virus (H3N2v) first identified in 2011. METHODS: We identified laboratory-confirmed cases of H3N2v and used a standard case report form to characterize illness and exposures. We considered illness to result from person-to-person H3N2v transmission if swine contact was not identified within 4 days prior to illness onset. RESULTS: From 9 July to 7 September 2012, we identified 306 cases of H3N2v in 10 states. The median age of all patients was 7 years. Commonly reported signs and symptoms included fever (98%), cough (85%), and fatigue (83%). Sixteen patients (5.2%) were hospitalized, and 1 fatal case was identified. The majority of those infected reported agricultural fair attendance (93%) and/or contact with swine (95%) prior to illness. We identified 15 cases of possible person-to-person transmission of H3N2v. Viruses recovered from patients were 93%-100% identical and similar to viruses recovered from previous cases of H3N2v. All H3N2v viruses examined were susceptible to oseltamivir and zanamivir and resistant to adamantane antiviral medications. CONCLUSIONS: In a large outbreak of variant influenza, the majority of infected persons reported exposures, suggesting that swine contact at an agricultural fair was a risk for H3N2v infection. We identified limited person-to-person H3N2v virus transmission, but found no evidence of efficient or sustained person-to-person transmission. Fair managers and attendees should be aware of the risk of swine-to-human transmission of influenza viruses in these settings. |
Antiviral susceptibility of highly pathogenic avian influenza A(H5N1) viruses isolated from poultry, Vietnam, 2009-2011
Nguyen HT , Nguyen T , Mishin VP , Sleeman K , Balish A , Jones J , Creanga A , Marjuki H , Uyeki TM , Nguyen DH , Nguyen DT , Do HT , Klimov AI , Davis CT , Gubareva LV . Emerg Infect Dis 2013 19 (12) 1963-71 We assessed drug susceptibilities of 125 avian influenza A(H5N1) viruses isolated from poultry in Vietnam during 2009-2011. Of 25 clade 1.1 viruses, all possessed a marker of resistance to M2 blockers amantadine and rimantadine; 24 were inhibited by neuraminidase inhibitors. One clade 1.1 virus contained the R430W neuraminidase gene and reduced inhibition by oseltamivir, zanamivir, and laninamivir 12-, 73-, and 29-fold, respectively. Three of 30 clade 2.3.4 viruses contained a I223T mutation and showed 7-fold reduced inhibition by oseltamivir. One of 70 clade 2.3.2.1 viruses had the H275Y marker of oseltamivir resistance and exhibited highly reduced inhibition by oseltamivir and peramivir; antiviral agents DAS181 and favipiravir inhibited H275Y mutant virus replication in MDCK-SIAT1 cells. Replicative fitness of the H275Y mutant virus was comparable to that of wildtype virus. These findings highlight the role of drug susceptibility monitoring of H5N1 subtype viruses circulating among birds to inform antiviral stockpiling decisions for pandemic preparedness. |
Emergence of multiple clade 2.3.2.1 influenza A (H5N1) virus subgroups in Vietnam and detection of novel reassortants
Creanga A , Thi Nguyen D , Gerloff N , Thi Do H , Balish A , Dang Nguyen H , Jang Y , Thi Dam V , Thor S , Jones J , Simpson N , Shu B , Emery S , Berman L , Nguyen HT , Bryant JE , Lindstrom S , Klimov A , Donis RO , Davis CT , Nguyen T . Virology 2013 444 12-20 Phylogenetic analyses of 169 influenza A(H5N1) virus genomes were conducted for samples collected through active surveillance and outbreak responses in Vietnam between September 2010 and September 2012. While clade 1.1 viruses persisted in southern regions, three genetically distinct subgroups of clade 2.3.2.1 were found in northern and central Vietnam. The identification of each subgroup corresponded with detection of novel reassortants, likely due to their overlapping circulation throughout the country. While the previously identified clade 1.1 and A/Hubei/1/2010-like 2.3.2.1 genotypes remained the predominant viruses detected, four viruses were found to be reassortants between A/Hubei/1/2010-like (HA, NA, PB2, PB1, PA, NP) and A/duck/Vietnam/NCVD-885/2010-like (M, NS) viruses and one virus was identified as having A/duck/Vietnam/NCVD-885/2010-like HA, NA, PB1, and NP with A/Hubei/1/2010-like PB2 and PA genes. Additionally, clade 2.3.2.1 A/Hong Kong/6841/2010-like viruses, first detected in mid-2012, were identified as reassortants comprised of A/Hubei/1/2010-like PB2 and PA and A/duck/Vietnam/NCVD-885/2010-like PB1, NP, NA, M, NS genes. |
A high diversity of Eurasian lineage low pathogenicity avian influenza A viruses circulate among wild birds sampled in Egypt
Gerloff NA , Jones J , Simpson N , Balish A , Elbadry MA , Baghat V , Rusev I , de Mattos CC , de Mattos CA , Zonkle LE , Kis Z , Davis CT , Yingst S , Cornelius C , Soliman A , Mohareb E , Klimov A , Donis RO . PLoS One 2013 8 (7) e68522 Surveillance for influenza A viruses in wild birds has increased substantially as part of efforts to control the global movement of highly pathogenic avian influenza A (H5N1) virus. Studies conducted in Egypt from 2003 to 2007 to monitor birds for H5N1 identified multiple subtypes of low pathogenicity avian influenza A viruses isolated primarily from migratory waterfowl collected in the Nile Delta. Phylogenetic analysis of 28 viral genomes was performed to estimate their nearest ancestors and identify possible reassortants. Migratory flyway patterns were included in the analysis to assess gene flow between overlapping flyways. Overall, the viruses were most closely related to Eurasian, African and/or Central Asian lineage low pathogenicity viruses and belonged to 15 different subtypes. A subset of the internal genes seemed to originate from specific flyways (Black Sea-Mediterranean, East African-West Asian). The remaining genes were derived from a mixture of viruses broadly distributed across as many as 4 different flyways suggesting the importance of the Nile Delta for virus dispersal. Molecular clock date estimates suggested that the time to the nearest common ancestor of all viruses analyzed ranged from 5 to 10 years, indicating frequent genetic exchange with viruses sampled elsewhere. The intersection of multiple migratory bird flyways and the resulting diversity of influenza virus gene lineages in the Nile Delta create conditions favoring reassortment, as evident from the gene constellations identified by this study. In conclusion, we present for the first time a comprehensive phylogenetic analysis of full genome sequences from low pathogenic avian influenza viruses circulating in Egypt, underscoring the significance of the region for viral reassortment and the potential emergence of novel avian influenza A viruses, as well as representing a highly diverse influenza A virus gene pool that merits continued monitoring. |
Analytical detection of influenza A(H3N2)v and other A variant viruses from the USA by rapid influenza diagnostic tests
Balish A , Garten R , Klimov A , Villanueva J . Influenza Other Respir Viruses 2013 7 (4) 491-6 BACKGROUND: The performance of rapid influenza diagnostic tests (RIDTs) that detect influenza viral nucleoprotein (NP) antigen has been reported to be variable. Recent human infections with variant influenza A viruses that are circulating in pigs prompted the investigation of the analytical reactivity of RIDTs with these variant viruses. OBJECTIVES: To determine analytical reactivity of seven FDA-cleared RIDTs with influenza A variant viruses in comparison with the reactivity with recently circulating seasonal influenza A viruses. METHODS: Tenfold serial dilutions of cell culture-grown seasonal and variant influenza A viruses were prepared and tested in duplicate with seven RIDTs. RESULTS: All RIDTs evaluated in this study detected the seasonal influenza A(H3N2) virus, although detection limits varied among assays. All but one examined RIDT identified the influenza A(H1N1)pdm09 virus. However, only four of seven RIDTs detected all influenza A(H3N2)v, A(H1N2)v, and A(H1N1)v viruses. Reduced sensitivity of RIDTs to variant influenza viruses may be due to amino acid differences between the NP proteins of seasonal viruses and the NP proteins from viruses circulating in pigs. CONCLUSIONS: Clinicians should be aware of the limitations of RIDTs to detect influenza A variant viruses. Specimens from patients with influenza-like illness in whom H3N2v is suspected should be sent to public health laboratories for additional diagnostic testing. |
Influenza: propagation, quantification, and storage
Balish AL , Katz JM , Klimov AI . Curr Protoc Microbiol 2013 Chapter 15 Unit15G 1 Influenza viruses are negative-sense, single-stranded, enveloped RNA viruses belonging to the family Orthomyxoviridae. Three types exist, influenza A, B, and C. All infect humans, but only A and B are major human pathogens. Influenza type A viruses are divided into subtypes based on genetic and antigenic differences in the two surface spike proteins, hemagglutinin (HA) and neuraminidase (NA). The appropriate cell lines to be used for isolation of influenza A or B viruses depend on the clinical information and the host of origin. MDCK cells are the preferred cell line for isolation of human influenza viruses from clinical specimens. (Curr. Protoc. Microbiol. 29:15G.1.1-15G.1.24. (c) 2013 by John Wiley & Sons, Inc.) |
Pathogenesis, transmissibility, and ocular tropism of a highly pathogenic avian influenza A (H7N3) virus associated with human conjunctivitis
Belser JA , Davis CT , Balish A , Edwards LE , Zeng H , Maines TR , Gustin KM , Martinez IL , Fasce R , Cox NJ , Katz JM , Tumpey TM . J Virol 2013 87 (10) 5746-54 H7 subtype influenza A viruses, responsible for numerous outbreaks in land-based poultry in Europe and the Americas, have caused over 100 cases of confirmed or presumed human infection over the last decade. The emergence of a highly pathogenic avian influenza H7N3 virus in poultry throughout the state of Jalisco, Mexico, resulting in two cases of human infection, prompted us to examine the virulence of this virus [A/Mexico/InDRE7218/2012 (MX/7218)] and related avian H7 subtype viruses in mouse and ferret models. Several high and low pathogenicity H7N3 and H7N9 viruses replicated efficiently in the respiratory tract of mice without prior adaptation following intranasal inoculation, but only MX/7218 virus caused lethal disease in this species. H7N3 and H7N9 viruses were also detected in the mouse eye following ocular inoculation. Virus from both H7N3 and H7N9 subtypes replicated efficiently in the upper and lower respiratory tract of ferrets, however, only MX/7218 virus infection caused clinical signs and symptoms and was capable of transmission to naive ferrets in a direct contact model. Similar to other highly pathogenic H7 viruses, MX/7218 replicated to high titers in human bronchial epithelial cells, yet downregulated numerous genes related to NF-kappaB-mediated signaling transduction. These findings indicate that the recently isolated North American lineage H7 subtype virus associated with human conjunctivitis is capable of causing severe disease in mice and spreading to naive contact ferrets, while concurrently retaining the ability to replicate within ocular tissue allowing the eye to serve as a portal of entry. |
Microevolution of highly pathogenic avian influenza A(H5N1) viruses isolated from humans, Egypt, 2007-2011
Younan M , Poh MK , Elassal E , Davis T , Rivailler P , Balish AL , Simpson N , Jones J , Deyde V , Loughlin R , Perry I , Gubareva L , Elbadry MA , Truelove S , Gaynor AM , Mohareb E , Amin M , Cornelius C , Pimentel G , Earhart K , Naguib A , Abdelghani AS , Refaey S , Klimov AI , Donis RO , Kandeel A . Emerg Infect Dis 2013 19 (1) 43-50 We analyzed highly pathogenic avian influenza A(H5N1) viruses isolated from humans infected in Egypt during 2007-2011. All analyzed viruses evolved from the lineage of subtype H5N1 viruses introduced into Egypt in 2006; we found minimal evidence of reassortment and no exotic introductions. The hemagglutinin genes of the viruses from 2011 formed a monophyletic group within clade 2.2.1 that also included human viruses from 2009 and 2010 and contemporary viruses from poultry; this finding is consistent with zoonotic transmission. Although molecular markers suggestive of decreased susceptibility to antiviral drugs were detected sporadically in the neuraminidase and matrix 2 proteins, functional neuraminidase inhibition assays did not identify resistant viruses. No other mutations suggesting a change in the threat to public health were detected in the viral proteomes. However, a comparison of representative subtype H5N1 viruses from 2011 with older subtype H5N1 viruses from Egypt revealed substantial antigenic drift. |
Prevalence of seropositivity to pandemic influenza A/H1N1 virus in the United States following the 2009 pandemic
Reed C , Katz JM , Hancock K , Balish A , Fry AM . PLoS One 2012 7 (10) e48187 BACKGROUND: 2009 pandemic influenza A/H1N1 (A(H1N1)pdm09) was first detected in the United States in April 2009 and resulted in a global pandemic. We conducted a serologic survey to estimate the cumulative incidence of A(H1N1)pdm09 through the end of 2009 when pandemic activity had waned in the United States. METHODS: We conducted a pair of cross sectional serologic surveys before and after the spring/fall waves of the pandemic for evidence of seropositivity (titer $40) using the hemagglutination inhibition (HI) assay. We tested a baseline sample of 1,142 serum specimens from the 2007-2008 National Health and Nutrition Examination Survey (NHANES), and 2,759 serum specimens submitted for routine screening to clinical diagnostic laboratories from ten representative sites. RESULTS: The age-adjusted prevalence of seropositivity to A(H1N1)pdm09 by year-end 2009 was 36.9% (95%CI: 31.7-42.2%). After adjusting for baseline cross-reactive antibody, pandemic vaccination coverage and the sensitivity/specificity of the HI assay, we estimate that 20.2% (95%CI: 10.1-28.3%) of the population was infected with A(H1N1)pdm09 by December 2009, including 53.3% (95%CI: 39.0-67.1%) of children aged 5-17 years. CONCLUSIONS: By December 2009, approximately one-fifth of the US population, or 61.9 million persons, may have been infected with A(H1N1)pdm09, including around half of school-aged children. |
Additional diagnostic yield of adding serology to PCR in diagnosing viral acute respiratory infections in Kenyan patients 5 years of age and older
Feikin DR , Njenga MK , Bigogo G , Aura B , Gikunju S , Balish A , Katz MA , Erdman D , Breiman RF . Clin Vaccine Immunol 2012 20 (1) 113-4 The role of serology in the setting of PCR-based diagnosis of acute respiratory infections (ARI) is unclear. We found acute- and convalescent-phase paired serologic testing increased the diagnostic yield beyond PCR of naso/oropharyngeal swabs for influenza virus, RSV, human metapneumovirus, adenovirus and parainfluenza viruses, by 0.4%-10.7%. Although still limited for clinical use, serology, along with PCR, can maximize etiologic diagnosis in epidemiologic studies. |
Evolution of highly pathogenic avian influenza (H5N1) virus populations in Vietnam between 2007 and 2010.
Nguyen T , Rivailler P , Davis CT , Thi Hoa D , Balish A , Hoang Dang N , Jones J , Thi Vui D , Simpson N , Thu Huong N , Shu B , Loughlin R , Ferdinand K , Lindstrom SE , York IA , Klimov A , Donis RO . Virology 2012 432 (2) 405-16 We report on the genetic analysis of 213 highly pathogenic avian influenza (HPAI) H5N1 viruses isolated from poultry in Vietnam between 2007 and 2010. Phylogenetic analyses of the viral genomes revealed 38 distinct viral genotypes, 29 were novel and 9 were reported in Vietnam or neighboring countries in recent years. Viruses from only six genotypes persisted beyond one season or year. Thus, most reassortant viruses were transient, suggesting that such genotypes lacked significant fitness advantages. Viruses with clade 2.3.2.1 HA were re-introduced into Vietnam in 2009 and their prevalence rose steeply towards the end of 2010. Clade 2.3.4-like viruses (genotype V) were predominant in northern Vietnam and caused the majority of zoonotic infections, whereas clade 1.1 (genotype Z) viruses were only detected in the Mekong delta region, in southern Vietnam. Antigenic analysis of representative viruses from the four clades indicated substantial drift. |
Etiology and incidence of viral and bacterial acute respiratory illness among older children and adults in rural western Kenya, 2007-2010
Feikin DR , Njenga MK , Bigogo G , Aura B , Aol G , Audi A , Jagero G , Muluare PO , Gikunju S , Nderitu L , Balish A , Winchell J , Schneider E , Erdman D , Oberste MS , Katz MA , Breiman RF . PLoS One 2012 7 (8) e43656 BACKGROUND: Few comprehensive data exist on disease incidence for specific etiologies of acute respiratory illness (ARI) in older children and adults in Africa. METHODOLOGY/PRINCIPAL FINDINGS: From March 1, 2007, to February 28, 2010, among a surveillance population of 21,420 persons >5 years old in rural western Kenya, we collected blood for culture and malaria smears, nasopharyngeal and oropharyngeal swabs for quantitative real-time PCR for ten viruses and three atypical bacteria, and urine for pneumococcal antigen testing on outpatients and inpatients meeting a ARI case definition (cough or difficulty breathing or chest pain and temperature >38.0 degrees C or oxygen saturation <90% or hospitalization). We also collected swabs from asymptomatic controls, from which we calculated pathogen-attributable fractions, adjusting for age, season, and HIV-status, in logistic regression. We calculated incidence by pathogen, adjusting for health-seeking for ARI and pathogen-attributable fractions. Among 3,406 ARI patients >5 years old (adjusted annual incidence 12.0 per 100 person-years), influenza A virus was the most common virus (22% overall; 11% inpatients, 27% outpatients) and Streptococcus pneumoniae was the most common bacteria (16% overall; 23% inpatients, 14% outpatients), yielding annual incidences of 2.6 and 1.7 episodes per 100 person-years, respectively. Influenza A virus, influenza B virus, respiratory syncytial virus (RSV) and human metapneumovirus were more prevalent in swabs among cases (22%, 6%, 8% and 5%, respectively) than controls. Adenovirus, parainfluenza viruses, rhinovirus/enterovirus, parechovirus, and Mycoplasma pneumoniae were not more prevalent among cases than controls. Pneumococcus and non-typhi Salmonella were more prevalent among HIV-infected adults, but prevalence of viruses was similar among HIV-infected and HIV-negative individuals. ARI incidence was highest during peak malaria season. CONCLUSIONS/SIGNFICANCE: Vaccination against influenza and pneumococcus (by potential herd immunity from childhood vaccination or of HIV-infected adults) might prevent much of the substantial ARI incidence among persons >5 years old in similar rural African settings. |
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