172 results on '"Agoti, Charles N"'
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152. Genomic epidemiology of human adenovirus F40 and F41 in coastal Kenya: A retrospective hospital-based surveillance study (2013-2022)
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Arnold W Lambisia, Timothy O Makori, Martin Mutunga, Robinson Cheruiyot, Nickson Murunga, Joshua Quick, George Githinji, D James Nokes, Charlotte J Houldcroft, Charles N Agoti, Lambisia, Arnold W [0000-0001-5312-0960], Makori, Timothy O [0000-0003-4482-9729], Githinji, George [0000-0001-9640-7371], Nokes, D James [0000-0001-5426-1984], Houldcroft, Charlotte J [0000-0002-1833-5285], Agoti, Charles N [0000-0002-2160-567X], and Apollo - University of Cambridge Repository
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Virology ,human adenovirus F ,Microbiology ,Kenya ,F40/41 ,recombination - Abstract
IntroductionHuman adenoviruses type F (HAdV-F) are leading cause of childhood diarrhoeal deaths. Genomic analysis would be key for understanding their potential drivers of disease severity, transmission dynamics, and for vaccine development. However, currently there is only limited data on HAdV-F genomes globally.MethodsHere, we sequenced and analysed HAdV-F from stool samples collected in coastal Kenya between 2013 and 2022. The samples were collected at Kilifi County Hospital in Kilifi, Kenya, from children < 13 years of age who reported a history of ≥ 3 loose stools in the previous 24hrs. The genomes were compared with data from the rest of the world by phylogenetic analysis and mutational profiling. Genotypes and lineages were assigned based on clustering on the global phylogenetic tree and from previously described nomenclature. Participant clinical and demographic data were linked to genotypic data.ResultsOf 91 cases identified using real-time PCR, 83 near-complete genomes were assembled, and these classified into HAdV-F40 and F41. These genotypes cocirculated throughout the study period. Three and four distinct lineages were observed for HAdV-F40 (Lineage 1-3) and F41 (Lineage 1, 2A, 3A, 3C and 3D). Genotype F40 and F41 coinfections were observed in five samples, and F41 and B7 in one sample. Two children with F40 and 41 coinfections were also infected with rotavirus and had moderate and severe disease, respectively. Intratypic recombination was found in 4 HAdV-F40 sequences occurring between lineages 1 and 3. None of the HAdV-F41 cases had jaundice.InterpretationThis study provides evidence of extensive genetic diversity, coinfections and recombination within HAdV-F40 in a high adenovirus transmission setting that will inform public health policy, vaccine development that includes the locally circulating lineages, and molecular diagnostic assay development. We recommend future comprehensive studies elucidating on HAdV-F genetic diversity and immunity for rational vaccine development.
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- 2023
153. The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.
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Tegally H, San JE, Cotten M, Moir M, Tegomoh B, Mboowa G, Martin DP, Baxter C, Lambisia AW, Diallo A, Amoako DG, Diagne MM, Sisay A, Zekri AN, Gueye AS, Sangare AK, Ouedraogo AS, Sow A, Musa AO, Sesay AK, Abias AG, Elzagheid AI, Lagare A, Kemi AS, Abar AE, Johnson AA, Fowotade A, Oluwapelumi AO, Amuri AA, Juru A, Kandeil A, Mostafa A, Rebai A, Sayed A, Kazeem A, Balde A, Christoffels A, Trotter AJ, Campbell A, Keita AK, Kone A, Bouzid A, Souissi A, Agweyu A, Naguib A, Gutierrez AV, Nkeshimana A, Page AJ, Yadouleton A, Vinze A, Happi AN, Chouikha A, Iranzadeh A, Maharaj A, Batchi-Bouyou AL, Ismail A, Sylverken AA, Goba A, Femi A, Sijuwola AE, Marycelin B, Salako BL, Oderinde BS, Bolajoko B, Diarra B, Herring BL, Tsofa B, Lekana-Douki B, Mvula B, Njanpop-Lafourcade BM, Marondera BT, Khaireh BA, Kouriba B, Adu B, Pool B, McInnis B, Brook C, Williamson C, Nduwimana C, Anscombe C, Pratt CB, Scheepers C, Akoua-Koffi CG, Agoti CN, Mapanguy CM, Loucoubar C, Onwuamah CK, Ihekweazu C, Malaka CN, Peyrefitte C, Grace C, Omoruyi CE, Rafaï CD, Morang'a CM, Erameh C, Lule DB, Bridges DJ, Mukadi-Bamuleka D, Park D, Rasmussen DA, Baker D, Nokes DJ, Ssemwanga D, Tshiabuila D, Amuzu DSY, Goedhals D, Grant DS, Omuoyo DO, Maruapula D, Wanjohi DW, Foster-Nyarko E, Lusamaki EK, Simulundu E, Ong'era EM, Ngabana EN, Abworo EO, Otieno E, Shumba E, Barasa E, Ahmed EB, Ahmed EA, Lokilo E, Mukantwari E, Philomena E, Belarbi E, Simon-Loriere E, Anoh EA, Manuel E, Leendertz F, Taweh FM, Wasfi F, Abdelmoula F, Takawira FT, Derrar F, Ajogbasile FV, Treurnicht F, Onikepe F, Ntoumi F, Muyembe FM, Ragomzingba FEZ, Dratibi FA, Iyanu FA, Mbunsu GK, Thilliez G, Kay GL, Akpede GO, van Zyl GU, Awandare GA, Kpeli GS, Schubert G, Maphalala GP, Ranaivoson HC, Omunakwe HE, Onywera H, Abe H, Karray H, Nansumba H, Triki H, Kadjo HAA, Elgahzaly H, Gumbo H, Mathieu H, Kavunga-Membo H, Smeti I, Olawoye IB, Adetifa IMO, Odia I, Ben Boubaker IB, Muhammad IA, Ssewanyana I, Wurie I, Konstantinus IS, Halatoko JWA, Ayei J, Sonoo J, Makangara JC, Tamfum JM, Heraud JM, Shaffer JG, Giandhari J, Musyoki J, Nkurunziza J, Uwanibe JN, Bhiman JN, Yasuda J, Morais J, Kiconco J, Sandi JD, Huddleston J, Odoom JK, Morobe JM, Gyapong JO, Kayiwa JT, Okolie JC, Xavier JS, Gyamfi J, Wamala JF, Bonney JHK, Nyandwi J, Everatt J, Nakaseegu J, Ngoi JM, Namulondo J, Oguzie JU, Andeko JC, Lutwama JJ, Mogga JJH, O'Grady J, Siddle KJ, Victoir K, Adeyemi KT, Tumedi KA, Carvalho KS, Mohammed KS, Dellagi K, Musonda KG, Duedu KO, Fki-Berrajah L, Singh L, Kepler LM, Biscornet L, de Oliveira Martins L, Chabuka L, Olubayo L, Ojok LD, Deng LL, Ochola-Oyier LI, Tyers L, Mine M, Ramuth M, Mastouri M, ElHefnawi M, Mbanne M, Matsheka MI, Kebabonye M, Diop M, Momoh M, Lima Mendonça MDL, Venter M, Paye MF, Faye M, Nyaga MM, Mareka M, Damaris MM, Mburu MW, Mpina MG, Owusu M, Wiley MR, Tatfeng MY, Ayekaba MO, Abouelhoda M, Beloufa MA, Seadawy MG, Khalifa MK, Matobo MM, Kane M, Salou M, Mbulawa MB, Mwenda M, Allam M, Phan MVT, Abid N, Rujeni N, Abuzaid N, Ismael N, Elguindy N, Top NM, Dia N, Mabunda N, Hsiao NY, Silochi NB, Francisco NM, Saasa N, Bbosa N, Murunga N, Gumede N, Wolter N, Sitharam N, Ndodo N, Ajayi NA, Tordo N, Mbhele N, Razanajatovo NH, Iguosadolo N, Mba N, Kingsley OC, Sylvanus O, Femi O, Adewumi OM, Testimony O, Ogunsanya OA, Fakayode O, Ogah OE, Oludayo OE, Faye O, Smith-Lawrence P, Ondoa P, Combe P, Nabisubi P, Semanda P, Oluniyi PE, Arnaldo P, Quashie PK, Okokhere PO, Bejon P, Dussart P, Bester PA, Mbala PK, Kaleebu P, Abechi P, El-Shesheny R, Joseph R, Aziz RK, Essomba RG, Ayivor-Djanie R, Njouom R, Phillips RO, Gorman R, Kingsley RA, Neto Rodrigues RMDESA, Audu RA, Carr RAA, Gargouri S, Masmoudi S, Bootsma S, Sankhe S, Mohamed SI, Femi S, Mhalla S, Hosch S, Kassim SK, Metha S, Trabelsi S, Agwa SH, Mwangi SW, Doumbia S, Makiala-Mandanda S, Aryeetey S, Ahmed SS, Ahmed SM, Elhamoumi S, Moyo S, Lutucuta S, Gaseitsiwe S, Jalloh S, Andriamandimby SF, Oguntope S, Grayo S, Lekana-Douki S, Prosolek S, Ouangraoua S, van Wyk S, Schaffner SF, Kanyerezi S, Ahuka-Mundeke S, Rudder S, Pillay S, Nabadda S, Behillil S, Budiaki SL, van der Werf S, Mashe T, Mohale T, Le-Viet T, Velavan TP, Schindler T, Maponga TG, Bedford T, Anyaneji UJ, Chinedu U, Ramphal U, George UE, Enouf V, Nene V, Gorova V, Roshdy WH, Karim WA, Ampofo WK, Preiser W, Choga WT, Ahmed YA, Ramphal Y, Bediako Y, Naidoo Y, Butera Y, de Laurent ZR, Ouma AEO, von Gottberg A, Githinji G, Moeti M, Tomori O, Sabeti PC, Sall AA, Oyola SO, Tebeje YK, Tessema SK, de Oliveira T, Happi C, Lessells R, Nkengasong J, and Wilkinson E
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- Africa epidemiology, Genomics, Humans, COVID-19 epidemiology, COVID-19 virology, Epidemiological Monitoring, Pandemics, SARS-CoV-2 genetics
- Abstract
Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century.
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- 2022
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154. Epidemiology of COVID-19 infections on routine polymerase chain reaction (PCR) and serology testing in Coastal Kenya.
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Nyagwange J, Ndwiga L, Muteru K, Wamae K, Tuju J, Testing Team C, Kutima B, Gitonga J, Karanja H, Mugo D, Kasera K, Amoth P, Murunga N, Babu L, Otieno E, Githinji G, Nokes DJ, Tsofa B, Orindi B, Barasa E, Warimwe G, Agoti CN, Bejon P, and Ochola-Oyier LI
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Background: There are limited studies in Africa describing the epidemiology, clinical characteristics and serostatus of individuals tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We tested routine samples from the Coastal part of Kenya between 17
th March 2020 and 30th June 2021. Methods: SARS-CoV-2 infections identified using reverse transcription polymerase chain reaction (RT-PCR) and clinical surveillance data at the point of sample collection were used to classify as either symptomatic or asymptomatic. IgG antibodies were measured in sera samples, using a well validated in-house enzyme-linked immunosorbent assay (ELISA). Results: Mombasa accounted for 56.2% of all the 99,694 naso-pharyngeal/oro-pharyngeal swabs tested, and males constituted the majority tested (73.4%). A total of 7737 (7.7%) individuals were SARS-CoV-2 positive by RT-PCR. The majority (i.e., 92.4%) of the RT-PCR positive individuals were asymptomatic. Testing was dominated by mass screening and travellers, and even at health facility level 91.6% of tests were from individuals without symptoms. Out of the 97,124 tests from asymptomatic individuals 7,149 (7%) were positive and of the 2,568 symptomatic individuals 588 (23%) were positive. In total, 2458 serum samples were submitted with paired naso-pharyngeal/oro-pharyngeal samples and 45% of the RT-PCR positive samples and 20% of the RT-PCR negative samples were paired with positive serum samples. Symptomatic individuals had significantly higher antibody levels than asymptomatic individuals and become RT-PCR negative on repeat testing earlier than asymptomatic individuals. Conclusions: In conclusion, the majority of SARS-CoV-2 infections identified by routine testing in Coastal Kenya were asymptomatic. This reflects the testing practice of health services in Kenya, but also implies that asymptomatic infection is very common in the population. Symptomatic infection may be less common, or it may be that individuals do not present for testing when they have symptoms., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Nyagwange J et al.)- Published
- 2022
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155. Seroprevalence of Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 Among Healthcare Workers in Kenya.
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Etyang AO, Lucinde R, Karanja H, Kalu C, Mugo D, Nyagwange J, Gitonga J, Tuju J, Wanjiku P, Karani A, Mutua S, Maroko H, Nzomo E, Maitha E, Kamuri E, Kaugiria T, Weru J, Ochola LB, Kilimo N, Charo S, Emukule N, Moracha W, Mukabi D, Okuku R, Ogutu M, Angujo B, Otiende M, Bottomley C, Otieno E, Ndwiga L, Nyaguara A, Voller S, Agoti CN, Nokes DJ, Ochola-Oyier LI, Aman R, Amoth P, Mwangangi M, Kasera K, Ng'ang'a W, Adetifa IMO, Wangeci Kagucia E, Gallagher K, Uyoga S, Tsofa B, Barasa E, Bejon P, Scott JAG, Agweyu A, and Warimwe GM
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- Antibodies, Viral, Bayes Theorem, Health Personnel, Humans, Kenya epidemiology, Seroepidemiologic Studies, Spike Glycoprotein, Coronavirus, COVID-19, SARS-CoV-2
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Background: Few studies have assessed the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among healthcare workers (HCWs) in Africa. We report findings from a survey among HCWs in 3 counties in Kenya., Methods: We recruited 684 HCWs from Kilifi (rural), Busia (rural), and Nairobi (urban) counties. The serosurvey was conducted between 30 July and 4 December 2020. We tested for immunoglobulin G antibodies to SARS-CoV-2 spike protein, using enzyme-linked immunosorbent assay. Assay sensitivity and specificity were 92.7 (95% CI, 87.9-96.1) and 99.0% (95% CI, 98.1-99.5), respectively. We adjusted prevalence estimates, using bayesian modeling to account for assay performance., Results: The crude overall seroprevalence was 19.7% (135 of 684). After adjustment for assay performance, seroprevalence was 20.8% (95% credible interval, 17.5%-24.4%). Seroprevalence varied significantly (P < .001) by site: 43.8% (95% credible interval, 35.8%-52.2%) in Nairobi, 12.6% (8.8%-17.1%) in Busia and 11.5% (7.2%-17.6%) in Kilifi. In a multivariable model controlling for age, sex, and site, professional cadre was not associated with differences in seroprevalence., Conclusion: These initial data demonstrate a high seroprevalence of antibodies to SARS-CoV-2 among HCWs in Kenya. There was significant variation in seroprevalence by region, but not by cadre., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)
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- 2022
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156. Global disparities in SARS-CoV-2 genomic surveillance.
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Brito AF, Semenova E, Dudas G, Hassler GW, Kalinich CC, Kraemer MUG, Ho J, Tegally H, Githinji G, Agoti CN, Matkin LE, Whittaker C, Howden BP, Sintchenko V, Zuckerman NS, Mor O, Blankenship HM, de Oliveira T, Lin RTP, Siqueira MM, Resende PC, Vasconcelos ATR, Spilki FR, Aguiar RS, Alexiev I, Ivanov IN, Philipova I, Carrington CVF, Sahadeo NSD, Gurry C, Maurer-Stroh S, Naidoo D, von Eije KJ, Perkins MD, van Kerkhove M, Hill SC, Sabino EC, Pybus OG, Dye C, Bhatt S, Flaxman S, Suchard MA, Grubaugh ND, Baele G, and Faria NR
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Genomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes >21 days after sample collection, and 77% of low and middle income countries sequenced <0.5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT <21 days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness.
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- 2021
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157. Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Immunoglobulin G Antibody Seroprevalence Among Truck Drivers and Assistants in Kenya.
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Kagucia EW, Gitonga JN, Kalu C, Ochomo E, Ochieng B, Kuya N, Karani A, Nyagwange J, Karia B, Mugo D, Karanja HK, Tuju J, Mutiso A, Maroko H, Okubi L, Maitha E, Ajuck H, Mukabi D, Moracha W, Bulimu D, Andanje N, Aman R, Mwangangi M, Amoth P, Kasera K, Ng'ang'a W, Nyaguara A, Voller S, Otiende M, Bottomley C, Agoti CN, Ochola-Oyier LI, Adetifa IMO, Etyang AO, Gallagher KE, Uyoga S, Barasa E, Bejon P, Tsofa B, Agweyu A, Warimwe GM, and Scott JAG
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In October 2020, anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G seroprevalence among truck drivers and their assistants (TDA) in Kenya was 42.3%, higher than among healthcare workers and blood donors. Truck drivers and their assistants transport essential supplies during the coronavirus disease 2019 pandemic, placing them at increased risk of being infected and of transmitting SARS-CoV-2 over a wide geographical area., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2021
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158. Near-Complete Genome Sequences of Eight Human Astroviruses Recovered from Diarrheal Stool Samples of Hospitalized Children in Coastal Kenya in 2019.
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Lambisia AW, Phan MVT, de Laurent ZR, Cotten M, Nokes DJ, and Agoti CN
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Here, using a sequence-independent sequencing approach (M. V. Phan, P. Hong Anh, N. Van Cuong, B. Oude Munnink, et al., Virus Evol 2:vew027, 2016, https://doi.org/10.1093/ve/vew027), we determined human astrovirus (HAstV) genome sequences from eight diarrheal stool samples collected in coastal Kenya in 2019. Phylogenetic analysis identified the following 4 genotypes: HAstV-1 ( n = 4), HAstV-2 ( n = 1), HAstV-3 ( n = 1), and HAstV-5 ( n = 2)., (Copyright © 2021 Lambisia et al.)
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- 2021
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159. Endemic chikungunya fever in Kenyan children: a prospective cohort study.
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Nyamwaya DK, Otiende M, Omuoyo DO, Githinji G, Karanja HK, Gitonga JN, R de Laurent Z, Otieno JR, Sang R, Kamau E, Cheruiyot S, Otieno E, Agoti CN, Bejon P, Thumbi SM, and Warimwe GM
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- Adolescent, Chikungunya Fever diagnosis, Chikungunya virus classification, Chikungunya virus genetics, Chikungunya virus isolation & purification, Child, Child, Preschool, Cross-Sectional Studies, Female, Fever diagnosis, Fever epidemiology, Fever virology, Genotype, Humans, Incidence, Infant, Kenya epidemiology, Male, Phylogeny, Prevalence, Prospective Studies, Recurrence, Chikungunya Fever epidemiology, Chikungunya Fever virology
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Background: Chikungunya fever (CHIKF) was first described in Tanzania in 1952. Several epidemics including East Africa have occurred, but there are no descriptions of longitudinal surveillance of endemic disease. Here, we estimate the incidence of CHIKF in coastal Kenya and describe the associated viral phylogeny., Methods: We monitored acute febrile illnesses among 3500 children visiting two primary healthcare facilities in coastal Kenya over a 5-year period (2014-2018). Episodes were linked to a demographic surveillance system and blood samples obtained. Cross-sectional sampling in a community survey of a different group of 435 asymptomatic children in the same study location was done in 2016. Reverse-transcriptase PCR was used for chikungunya virus (CHIKV) screening, and viral genomes sequenced for phylogenetic analyses., Results: We found CHIKF to be endemic in this setting, associated with 12.7% (95% CI 11.60, 13.80) of all febrile presentations to primary healthcare. The prevalence of CHIKV infections among asymptomatic children in the community survey was 0.7% (95% CI 0.22, 2.12). CHIKF incidence among children < 1 year of age was 1190 cases/100,000-person years and 63 cases/100,000-person years among children aged ≥10 years. Recurrent CHIKF episodes, associated with fever and viraemia, were observed among 19 of 170 children with multiple febrile episodes during the study period. All sequenced viral genomes mapped to the ECSA genotype albeit distinct from CHIKV strains associated with the 2004 East African epidemic., Conclusions: CHIKF may be a substantial public health burden in primary healthcare on the East African coast outside epidemic years, and recurrent infections are common.
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- 2021
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160. Integrating epidemiological and genetic data with different sampling intensities into a dynamic model of respiratory syncytial virus transmission.
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Kombe IK, Agoti CN, Munywoki PK, Baguelin M, Nokes DJ, and Medley GF
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- Adolescent, Bayes Theorem, Child, Child, Preschool, Family Characteristics, Female, Humans, Infant, Infant, Newborn, Kenya epidemiology, Male, Models, Theoretical, Respiratory Syncytial Virus, Human pathogenicity, Respiratory Syncytial Viruses pathogenicity, Stochastic Processes, Respiratory Syncytial Virus Infections epidemiology, Respiratory Syncytial Virus Infections genetics, Respiratory Syncytial Virus Infections transmission
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Respiratory syncytial virus (RSV) is responsible for a significant burden of severe acute lower respiratory tract illness in children under 5 years old; particularly infants. Prior to rolling out any vaccination program, identification of the source of infant infections could further guide vaccination strategies. We extended a dynamic model calibrated at the individual host level initially fit to social-temporal data on shedding patterns to include whole genome sequencing data available at a lower sampling intensity. The study population was 493 individuals (55 aged < 1 year) distributed across 47 households, observed through one RSV season in coastal Kenya. We found that 58/97 (60%) of RSV-A and 65/125 (52%) of RSV-B cases arose from infection probably occurring within the household. Nineteen (45%) infant infections appeared to be the result of infection by other household members, of which 13 (68%) were a result of transmission from a household co-occupant aged between 2 and 13 years. The applicability of genomic data in studies of transmission dynamics is highly context specific; influenced by the question, data collection protocols and pathogen under investigation. The results further highlight the importance of pre-school and school-aged children in RSV transmission, particularly the role they play in directly infecting the household infant. These age groups are a potential RSV vaccination target group.
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- 2021
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161. Evolution of respiratory syncytial virus genotype BA in Kilifi, Kenya, 15 years on.
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Kamau E, Otieno JR, Lewa CS, Mwema A, Murunga N, Nokes DJ, and Agoti CN
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- Amino Acid Sequence, Conserved Sequence, Epidemics, Genetic Variation, Genotype, Glycosylation, Humans, Kenya epidemiology, Markov Chains, Phylogeny, Protein Domains, Respiratory Syncytial Virus Infections epidemiology, Respiratory Syncytial Virus Infections virology, Viral Proteins chemistry, Biological Evolution, Respiratory Syncytial Virus, Human genetics
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Respiratory syncytial virus (RSV) is recognised as a leading cause of severe acute respiratory disease and deaths among infants and vulnerable adults. Clinical RSV isolates can be divided into several known genotypes. RSV genotype BA, characterised by a 60-nucleotide duplication in the G glycoprotein gene, emerged in 1999 and quickly disseminated globally replacing other RSV group B genotypes. Continual molecular epidemiology is critical to understand the evolutionary processes maintaining the success of the BA viruses. We analysed 735 G gene sequences from samples collected from paediatric patients in Kilifi, Kenya, between 2003 and 2017. The virus population comprised of several genetically distinct variants (n = 56) co-circulating within and between epidemics. In addition, there was consistent seasonal fluctuations in relative genetic diversity. Amino acid changes increasingly accumulated over the surveillance period including two residues (N178S and Q180R) that mapped to monoclonal antibody 2D10 epitopes, as well as addition of putative N-glycosylation sequons. Further, switching and toggling of amino acids within and between epidemics was observed. On a global phylogeny, the BA viruses from different countries form geographically isolated clusters suggesting substantial localized variants. This study offers insights into longitudinal population dynamics of a globally endemic RSV genotype within a discrete location.
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- 2020
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162. Rotavirus group A genotype circulation patterns across Kenya before and after nationwide vaccine introduction, 2010-2018.
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Mwanga MJ, Owor BE, Ochieng JB, Ngama MH, Ogwel B, Onyango C, Juma J, Njeru R, Gicheru E, Otieno GP, Khagayi S, Agoti CN, Bigogo GM, Omore R, Addo OY, Mapaseka S, Tate JE, Parashar UD, Hunsperger E, Verani JR, Breiman RF, and Nokes DJ
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- Child, Child, Preschool, Enzyme-Linked Immunosorbent Assay, Feces virology, Female, Gastroenteritis etiology, Humans, Immunization Schedule, Infant, Kenya epidemiology, Male, Phylogeny, Prevalence, Rotavirus Infections virology, Rotavirus Vaccines adverse effects, Rotavirus Vaccines immunology, Vaccines, Attenuated adverse effects, Vaccines, Attenuated immunology, Vaccines, Attenuated therapeutic use, Genotype, Rotavirus genetics, Rotavirus immunology, Rotavirus Infections epidemiology, Rotavirus Infections prevention & control, Rotavirus Vaccines therapeutic use, Vaccination
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Background: Kenya introduced the monovalent G1P [8] Rotarix® vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010-June 2014) and post- (July 2014-December 2018) RVA vaccine introduction., Methods: Stool samples were collected from children aged < 13 years from four surveillance sites across Kenya: Kilifi County Hospital, Tabitha Clinic Nairobi, Lwak Mission Hospital, and Siaya County Referral Hospital (children aged < 5 years only). Samples were screened for RVA using enzyme linked immunosorbent assay (ELISA) and VP7 and VP4 genes sequenced to infer genotypes., Results: We genotyped 614 samples in pre-vaccine and 261 in post-vaccine introduction periods. During the pre-vaccine introduction period, the most frequent RVA genotypes were G1P [8] (45.8%), G8P [4] (15.8%), G9P [8] (13.2%), G2P [4] (7.0%) and G3P [6] (3.1%). In the post-vaccine introduction period, the most frequent genotypes were G1P [8] (52.1%), G2P [4] (20.7%) and G3P [8] (16.1%). Predominant genotypes varied by year and site in both pre and post-vaccine periods. Temporal genotype patterns showed an increase in prevalence of vaccine heterotypic genotypes, such as the commonly DS-1-like G2P [4] (7.0 to 20.7%, P < .001) and G3P [8] (1.3 to 16.1%, P < .001) genotypes in the post-vaccine introduction period. Additionally, we observed a decline in prevalence of genotypes G8P [4] (15.8 to 0.4%, P < .001) and G9P [8] (13.2 to 5.4%, P < .001) in the post-vaccine introduction period. Phylogenetic analysis of genotype G1P [8], revealed circulation of strains of lineages G1-I, G1-II and P [8]-1, P [8]-III and P [8]-IV. Considerable genetic diversity was observed between the pre and post-vaccine strains, evidenced by distinct clusters., Conclusion: Genotype prevalence varied from before to after vaccine introduction. Such observations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full genome sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity.
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- 2020
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163. Correction to: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia.
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Kamau E, Oketch JW, de Laurent ZR, Phan MVT, Agoti CN, Nokes DJ, and Cotten M
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Following the publication of this article [1], it was noted that due to a typesetting error the figure legends were paired incorrectly.
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- 2020
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164. Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia.
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Kamau E, Oketch JW, de Laurent ZR, Phan MVT, Agoti CN, Nokes DJ, and Cotten M
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- Amino Acid Sequence, Genotype, Humans, Kenya epidemiology, Metapneumovirus pathogenicity, Paramyxoviridae Infections epidemiology, Paramyxoviridae Infections virology, Phylogeny, Viral Proteins genetics, Zambia epidemiology, Genome, Viral genetics, Metapneumovirus genetics, Paramyxoviridae Infections genetics, Whole Genome Sequencing
- Abstract
Background: Human metapneumovirus (HMPV) is an important cause of acute respiratory illness in young children. Whole genome sequencing enables better identification of transmission events and outbreaks, which is not always possible with sub-genomic sequences., Results: We report a 2-reaction amplicon-based next generation sequencing method to determine the complete genome sequences of five HMPV strains, representing three subgroups (A2, B1 and B2), directly from clinical samples. In addition to reporting five novel HMPV genomes from Africa we examined genetic diversity and sequence patterns of publicly available HMPV genomes. We found that the overall nucleotide sequence identity was 71.3 and 80% for HMPV group A and B, respectively, the diversity between HMPV groups was greater at amino acid level for SH and G surface protein genes, and multiple subgroups co-circulated in various countries. Comparison of sequences between HMPV groups revealed variability in G protein length (219 to 241 amino acids) due to changes in the stop codon position. Genome-wide phylogenetic analysis showed congruence with the individual gene sequence sets except for F and M2 genes., Conclusion: This is the first genomic characterization of HMPV genomes from African patients.
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- 2020
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165. Human metapneumovirus prevalence and patterns of subgroup persistence identified through surveillance of pediatric pneumonia hospital admissions in coastal Kenya, 2007-2016.
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Oketch JW, Kamau E, Otieno GP, Otieno JR, Agoti CN, and Nokes DJ
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- Age of Onset, Child, Preschool, Epidemics, Female, Genotype, Hospitals, Pediatric statistics & numerical data, Humans, Infant, Infant, Newborn, Kenya epidemiology, Male, Metapneumovirus genetics, Patient Admission statistics & numerical data, Phylogeny, Population Surveillance, Prevalence, Real-Time Polymerase Chain Reaction, Seasons, Metapneumovirus classification, Metapneumovirus isolation & purification, Paramyxoviridae Infections epidemiology, Paramyxoviridae Infections virology, Pneumonia epidemiology, Pneumonia virology
- Abstract
Background: Human metapneumovirus (HMPV) is an important respiratory pathogen that causes seasonal epidemics of acute respiratory illness and contributes significantly to childhood pneumonia. Current knowledge and understanding on its patterns of spread, prevalence and persistence in communities in low resource settings is limited., Methods: We present findings of a molecular-epidemiological analysis of nasal samples from children < 5 years of age admitted with syndromic pneumonia between 2007 and 2016 to Kilifi County Hospital, coastal Kenya. HMPV infection was detected using real-time RT-PCR and positives sequenced in the fusion (F) and attachment (G) genes followed by phylogenetic analysis. The association between disease severity and HMPV subgroup was assessed using Fisher's exact test., Results: Over 10 years, 274/6756 (4.1%) samples screened were HMPV positive. Annual prevalence fluctuated between years ranging 1.2 to 8.7% and lowest in the recent years (2014-2016). HMPV detections were most frequent between October of one year to April of the following year. Genotyping was successful for 205/274 (74.8%) positives revealing clades A2b (41.0%) and A2c (10.7%), and subgroups B1 (23.4%) and B2 (24.9%). The dominance patterns were: clade A2b between 2007 and 11, subgroup B1 between 2012 and 14, and clade A2c in more recent epidemics. Subgroup B2 viruses were present in all the years. Temporal phylogenetic clustering within the subgroups for both local and global sequence data was seen. Subgroups occurring in each epidemic season were comprised of multiple variants. Pneumonia severity did not vary by subgroup (p = 0.264). In both the F and G gene, the sequenced regions were found to be predominantly under purifying selection., Conclusion: Subgroup patterns from this rural African setting temporally map with global strain distribution, suggesting a well-mixed global virus transmission pool of HMPV. Persistence in the local community is characterized by repeated introductions of HMPV variants from the global pool. The factors underlying the declining prevalence of HMPV in this population should be investigated.
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- 2019
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166. Continuous Invasion by Respiratory Viruses Observed in Rural Households During a Respiratory Syncytial Virus Seasonal Outbreak in Coastal Kenya.
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Munywoki PK, Koech DC, Agoti CN, Cane PA, Medley GF, and Nokes DJ
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- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Coinfection epidemiology, Family Characteristics, Female, Humans, Infant, Kenya epidemiology, Male, Middle Aged, Multiplex Polymerase Chain Reaction, Nasopharynx virology, Public Health Surveillance, Respiratory Syncytial Virus Infections transmission, Respiratory Syncytial Virus, Human isolation & purification, Respiratory Tract Infections epidemiology, Respiratory Tract Infections transmission, Seasons, Viruses genetics, Viruses isolation & purification, Young Adult, Coinfection virology, Disease Outbreaks, Respiratory Syncytial Virus Infections epidemiology, Respiratory Tract Infections virology, Rural Population
- Abstract
Background: Households are high-intensity close-contact environments favorable for transmission of respiratory viruses, yet little is known for low-income settings., Methods: Active surveillance was completed on 47 households in rural coastal Kenya over 6 months during a respiratory syncytial virus (RSV) season. Nasopharyngeal swabs (NPSs) were taken from 483 household members twice weekly irrespective of symptoms. Using molecular diagnostics, NPSs from 6 households were screened for 15 respiratory viruses and the remainder of households only for the most frequent viruses observed: rhinovirus (RV), human coronavirus (HCoV; comprising strains 229E, OC43, and NL63), adenovirus (AdV), and RSV (A and B)., Results: Of 16928 NPSs tested for the common viruses, 4259 (25.2%) were positive for ≥1 target; 596 (13.8%) had coinfections. Detection frequencies were 10.5% RV (1780), 7.5% HCoV (1274), 7.3% AdV (1232), and 3.2% RSV (537). On average, each household and individual had 6 and 3 different viruses detected over the study period, respectively. Rhinovirus and HCoV were detected in all the 47 households while AdV and RSV were detected in 45 (95.7%) and 40 (85.1%) households, respectively. The individual risk of infection over the 6-month period was 93.4%, 80.1%, 71.6%, 61.5%, and 37.1% for any virus, RV, HCoV, AdV, and RSV, respectively. NPSs collected during symptomatic days and from younger age groups had higher prevalence of virus detection relative to respective counterparts. RSV was underrepresented in households relative to hospital admission data., Conclusions: In this household setting, respiratory virus infections and associated illness are ubiquitous. Future studies should address the health and economic implications of these observations.
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- 2018
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167. Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya.
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Kiyuka PK, Agoti CN, Munywoki PK, Njeru R, Bett A, Otieno JR, Otieno GP, Kamau E, Clark TG, van der Hoek L, Kellam P, Nokes DJ, and Cotten M
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- Adolescent, Adult, Biological Evolution, Child, Child, Preschool, Coronavirus Infections virology, Coronavirus OC43, Human genetics, Female, Hospitalization, Humans, Infant, Infant, Newborn, Kenya epidemiology, Male, Molecular Epidemiology, Phylogeny, Prevalence, Prospective Studies, Respiratory Tract Infections epidemiology, Respiratory Tract Infections virology, Young Adult, Coronavirus Infections epidemiology, Coronavirus NL63, Human genetics
- Abstract
Background: Human coronavirus NL63 (HCoV-NL63) is a globally endemic pathogen causing mild and severe respiratory tract infections with reinfections occurring repeatedly throughout a lifetime., Methods: Nasal samples were collected in coastal Kenya through community-based and hospital-based surveillance. HCoV-NL63 was detected with multiplex real-time reverse transcription PCR, and positive samples were targeted for nucleotide sequencing of the spike (S) protein. Additionally, paired samples from 25 individuals with evidence of repeat HCoV-NL63 infection were selected for whole-genome virus sequencing., Results: HCoV-NL63 was detected in 1.3% (75/5573) of child pneumonia admissions. Two HCoV-NL63 genotypes circulated in Kilifi between 2008 and 2014. Full genome sequences formed a monophyletic clade closely related to contemporary HCoV-NL63 from other global locations. An unexpected pattern of repeat infections was observed with some individuals showing higher viral titers during their second infection. Similar patterns for 2 other endemic coronaviruses, HCoV-229E and HCoV-OC43, were observed. Repeat infections by HCoV-NL63 were not accompanied by detectable genotype switching., Conclusions: In this coastal Kenya setting, HCoV-NL63 exhibited low prevalence in hospital pediatric pneumonia admissions. Clade persistence with low genetic diversity suggest limited immune selection, and absence of detectable clade switching in reinfections indicates initial exposure was insufficient to elicit a protective immune response.
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- 2018
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168. Spread and Evolution of Respiratory Syncytial Virus A Genotype ON1, Coastal Kenya, 2010-2015.
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Otieno JR, Kamau EM, Agoti CN, Lewa C, Otieno G, Bett A, Ngama M, Cane PA, and Nokes DJ
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- Amino Acid Substitution, Child, Preschool, Female, Genetic Variation, History, 21st Century, Humans, Infant, Infant, Newborn, Kenya epidemiology, Male, Odds Ratio, Phylogeny, Public Health Surveillance, Respiratory Syncytial Virus Infections diagnosis, Respiratory Syncytial Virus Infections history, Respiratory Syncytial Virus, Human classification, Sequence Analysis, DNA, Viral Envelope Proteins genetics, Evolution, Molecular, Genotype, Respiratory Syncytial Virus Infections epidemiology, Respiratory Syncytial Virus Infections virology, Respiratory Syncytial Virus, Human genetics
- Abstract
In February 2012, the novel respiratory syncytial virus (RSV) group A, genotype ON1, was detected in Kilifi County, coastal Kenya. ON1 is characterized by a 72-nt duplication within the highly variable G gene (encoding the immunogenic attachment surface protein). Cases were diagnosed through surveillance of pneumonia in children at the county hospital. Analysis of epidemiologic, clinical, and sequence data of RSV-A viruses detected over 5 RSV seasons (2010/2011 to 2014/2015) indicated the following: 1) replacement of previously circulating genotype GA2 ON1, 2) an abrupt expansion in the number of ON1 variants detected in the 2014/2015 epidemic, 3) recently accumulation of amino acid substitutions within the ON1 duplicated sequence, and 4) no clear evidence of altered pathogenicity relative to GA2. The study demonstrates the public health importance of molecular surveillance in defining the spread, clinical effects, and evolution of novel respiratory virus variants.
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- 2017
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169. Frequent Asymptomatic Respiratory Syncytial Virus Infections During an Epidemic in a Rural Kenyan Household Cohort.
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Munywoki PK, Koech DC, Agoti CN, Bett A, Cane PA, Medley GF, and Nokes DJ
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- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Family Characteristics, Female, Humans, Infant, Infant, Newborn, Kenya epidemiology, Male, Middle Aged, Prospective Studies, Rural Population statistics & numerical data, Young Adult, Asymptomatic Infections epidemiology, Epidemics statistics & numerical data, Respiratory Syncytial Virus Infections epidemiology
- Abstract
Background: The characteristics, determinants, and potential contribution to transmission of asymptomatic cases of respiratory syncytial virus (RSV) infection have not been well described., Methods: A cohort of 47 households (493 individuals) in coastal Kenya was recruited and followed for a 26-week period spanning a complete RSV season. Nasopharyngeal swab specimens were requested weekly, during the first 4 weeks, and twice weekly thereafter from all household members, regardless of illness status. The samples were screened for a range of respiratory viruses by multiplex real-time polymerase chain reaction., Results: Tests on 16,928 samples yielded 205 RSV infection episodes in 179 individuals (37.1%) from 40 different households. Eighty-six episodes (42.0%) were asymptomatic. Factors independently associated with an increased risk of asymptomatic RSV infection episodes were higher age, shorter duration of infection, bigger household size, lower peak viral load, absence of concurrent RSV infections within the household, infection by RSV group B, and no prior human rhinovirus infections. The propensity of RSV spread in households was dependent on symptom status and amount (duration and load) of virus shed., Conclusions: While asymptomatic RSV was less likely to spread, the high frequency of symptomless RSV infection episodes highlights a potentially important role of asymptomatic infections in the community transmission of RSV., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)
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- 2015
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170. The source of respiratory syncytial virus infection in infants: a household cohort study in rural Kenya.
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Munywoki PK, Koech DC, Agoti CN, Lewa C, Cane PA, Medley GF, and Nokes DJ
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- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Family, Family Characteristics, Female, Humans, Infant, Infant, Newborn, Kenya epidemiology, Male, Phylogeny, Respiratory Syncytial Virus Infections transmission, Respiratory Syncytial Virus Infections virology, Respiratory Syncytial Viruses genetics, Rural Population, Young Adult, Nasopharynx virology, Respiratory Syncytial Virus Infections epidemiology, Respiratory Syncytial Viruses isolation & purification
- Abstract
Background: Respiratory syncytial virus (RSV) vaccine development for direct protection of young infants faces substantial obstacles. Assessing the potential of indirect protection using different strategies, such as targeting older children or mothers, requires knowledge of the source of infection to the infants., Methods: We undertook a prospective study in rural Kenya. Households with a child born after the preceding RSV epidemic and ≥ 1 elder sibling were recruited. Nasopharyngeal swab samples were collected every 3-4 days irrespective of symptoms from all household members throughout the RSV season of 2009-2010 and tested for RSV using molecular techniques., Results: From 451 participants in 44 households a total of 15 396 nasopharyngeal swab samples were samples were collected, representing 86% of planned sampling. RSV was detected in 37 households (84%) and 173 participants (38%) and 28 study infants (64%). The infants acquired infection from within (15 infants; 54%) or outside (9 infants; 32%) the household; in 4 households the source of infant infection was inconclusive. Older children were index case patients for 11 (73%) of the within-household infant infections, and 10 of these 11 children were attending school., Conclusion: We demonstrate that school-going siblings frequently introduce RSV into households, leading to infection in infants.
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- 2014
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171. Examining strain diversity and phylogeography in relation to an unusual epidemic pattern of respiratory syncytial virus (RSV) in a long-term refugee camp in Kenya.
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Agoti CN, Mayieka LM, Otieno JR, Ahmed JA, Fields BS, Waiboci LW, Nyoka R, Eidex RB, Marano N, Burton W, Montgomery JM, Breiman RF, and Nokes DJ
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- Child, Preschool, Female, Genetic Variation, Genotype, Humans, Infant, Kenya epidemiology, Male, Phylogeography, Respiratory Syncytial Viruses classification, Respiratory Syncytial Viruses genetics, Epidemics, Refugees statistics & numerical data, Respiratory Syncytial Virus Infections epidemiology, Respiratory Syncytial Virus Infections virology, Respiratory Syncytial Viruses isolation & purification
- Abstract
Background: A recent longitudinal study in the Dadaab refugee camp near the Kenya-Somalia border identified unusual biannual respiratory syncytial virus (RSV) epidemics. We characterized the genetic variability of the associated RSV strains to determine if viral diversity contributed to this unusual epidemic pattern., Methods: For 336 RSV positive specimens identified from 2007 through 2011 through facility-based surveillance of respiratory illnesses in the camp, 324 (96.4%) were sub-typed by PCR methods, into 201 (62.0%) group A, 118 (36.4%) group B and 5 (1.5%) group A-B co-infections. Partial sequencing of the G gene (coding for the attachment protein) was completed for 290 (89.5%) specimens. These specimens were phylogenetically analyzed together with 1154 contemporaneous strains from 22 countries., Results: Of the 6 epidemic peaks recorded in the camp over the period, the first and last were predominantly made up of group B strains, while the 4 in between were largely composed of group A strains in a consecutive series of minor followed by major epidemics. The Dadaab group A strains belonged to either genotype GA2 (180, 98.9%) or GA5 (2, < 1%) while all group B strains (108, 100%) belonged to BA genotype. In sequential epidemics, strains within these genotypes appeared to be of two types: those continuing from the preceding epidemics and those newly introduced. Genotype diversity was similar in minor and major epidemics., Conclusion: RSV strain diversity in Dadaab was similar to contemporaneous diversity worldwide, suggested both between-epidemic persistence and new introductions, and was unrelated to the unusual epidemic pattern.
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- 2014
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172. Genetic relatedness of infecting and reinfecting respiratory syncytial virus strains identified in a birth cohort from rural Kenya.
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Agoti CN, Mwihuri AG, Sande CJ, Onyango CO, Medley GF, Cane PA, and Nokes DJ
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- Child, Cluster Analysis, Cohort Studies, Epidemics, Genetic Variation, Genotype, Humans, Kenya epidemiology, Likelihood Functions, Molecular Sequence Data, Phylogeny, Prevalence, RNA, Viral chemistry, Recurrence, Respiratory Syncytial Virus Infections epidemiology, Respiratory Syncytial Viruses classification, Rural Population, Respiratory Syncytial Virus Infections virology, Respiratory Syncytial Viruses genetics
- Abstract
Background: Respiratory syncytial virus (RSV) reinfects individuals repeatedly. The extent to which this is a consequence of RSV antigenic diversity is unclear., Methods: Six-hundred thirty-five children from rural Kenya were closely monitored for RSV infection from birth through 3 consecutive RSV epidemics. RSV infections were identified by immunofluorescence testing of nasal washing samples collected during acute respiratory illnesses, typed into group A and B, and sequenced in the attachment (G) protein. A positive sample separated from a previous positive by ≥14 days was defined as a reinfection a priori., Results: Phylogenetic analysis was undertaken for 325 (80%) of 409 identified infections, including 53 (64%) of 83 reinfections. Heterologous group reinfections were observed in 28 episodes, and homologous group reinfections were observed in 25 episodes; 10 involved homologous genotypes, 5 showed no amino acid changes, and 3 were separated by 21-24 days and were potentially persistent infections. The temporal distribution of genotypes among reinfections did not differ from that of single infections., Conclusions: The vast majority of infection and reinfection pairs differed by group, genotype, or G amino acid sequence (ie, comprised distinct viruses). The extent to which this is a consequence of immune memory of infection history or prevalent diversity remains unclear.
- Published
- 2012
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