Posted on Authorea 14 Aug 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. neihla el n aiiae h eerto ftevrsit h otcell host the into virus expressed the receptor NS2, chemokine of CX3CR1 NS1, penetration the the the to virus facilitates proteins: the and 11 of attachment cells for the epithelial code in that involved on proteins is genes L G 10 and glycoprotein contains The M2-2 genome M1-2, antibodies The F, neutralising G, of (bp). SH, pairs M, base P, in N, 000 million 15 about 20 of including 1995-2010, species order between winter the the worldwide the to deaths during belongs countries million particularly RSV tropical 90 pneumonia, in than and season alone more bronchiolitis rainy Africa for of the sub-Saharan cause responsible during leading be and second countries to the temperate is in months It 1956 infants. in characterized in first (RSV), virus syncytial Respiratory Introduction genetic This burden, Conclusion: RSV into insights observed. first were of provides ON1 predominance and country. CAF to alternating in the NA1 an RSV in from with of seasonality 2015, replacement analysis RSV-B and in epidemiological diversity genotype and in-depth seasons RSV-A RSV-A first RSV incidence the temporal of RSV While represents and circulation higher study significant Concomitant strains significantly fluctuations. with with RSV-B shown, season) patterns earlier. was and overall dry months 2015-2018 the RSV-A in 3-5 of from deviations 3.0% incidence period showed the vs peak 2017 in similar, and season 8.0% relatively rainy were of in 2018 RSV and (12.7% of 2016 prevalence seasonal overall and of An presence sequencing. (6.4%-10.6%) 6.4%). Sanger The annual vs and infants typing (9.5% strains. in –B patients RSV higher and male characterise RSV-A significantly in by to was followed RT-PCR, as incidence by 2018 well RSV assessed December as was to Results: samples severity 2015 nasopharyngeal disease January in and from RNA in of (ILI, recruited seasonality viral advantage illness infections were RSV prevalence, Taking influenza-like definitions the RSV respiratory Methods: case matching annual years 31.5%) (CAF). acute 5 determine (SARI, Republic under causing infection to African children respiratory Central pathogens 3903 acute of in viral severe total studied or a main been CAF, 68.5%) in seldom the network has surveillance of influenza but national age, one the of is years (RSV) 5 under virus children syncytial Respiratory Background: Abstract 2020 14, August 3 2 1 Muller 2018 KOMOYO to Giscard 2015 Republic, in African infections Central virus in syncytial children respiratory of severity and Prevalence uebugIsiueo Health of Bangui Institute de Luxembourg Universitaire Hospitalier National Centre Bangui de Pasteur Institut 3 uihHuebschen Judith , ua orthopneumovirus Human 1 rc YAMBIYO Brice , 7,8 9 h rti oen h uino h ia neoewt h elmembrane. cell the with envelope viral the of fusion the governs protein F The . Mononegavirales . 3 maulNakoun´e Emmanuel , ti nevlpdvrs ihalna,ngtv-es N genome RNA negative-sense linear, a with virus, enveloped an is It . h family the , 1 lxnr Manirakiza Alexandre , 5 h ufc lcpoen n r h antargets main the are F and G glycoproteins surface The . < ots(34) nhsiaie hlrn(33 s55)and 5.5%) vs (13.3% children hospitalized in (13.4%), months 6 1 Pneumoviridae 1 n hna Snoeck Chantal and , 1 fe asslwrrsiaoytatinfections tract respiratory lower causes often , h genus the , 1 enGody Jean , 10 2-6 h aiblt fthe of variability The . 3 Orthopneumovirus S a estimated was RSV . 2 Claude , and Posted on Authorea 14 Aug 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. S oiiesmlswr hntpda S- r- ytreigfso rti yasemi-nested U/ a 5 by with out F carried protein was fusion μ amplification targeting round (5’-GTTATGACACTGGTATACCAACC-3’) by first F164 The -B primer anti-sense or the RSV-A and as USA) (Invitrogen, typed before described then as were PCR samples positive RSV sequencing and typing RSV a by performed B 94 was influenza of detection and cycles RSV A 40 by influenza before protocol. metapneumovirus, described manufacturer’s human as detecting the virus RT-PCR to one-step according multiplex USA) conventional 140 (QIAGEN, a kit from Mini RT-PCR extracted by was detection RNA RSV and extraction acid for acids recorded Nucleic nucleic were of data extraction epidemiological culture, questionnaire. and sample virus standardised clinical Each influenza a sent demographic, diagnosis. for using or Social, for patient 4degC tubes -80degC. Influenza each at Eppendorf at for stored mL storage (NRC) a and 1.5 Centre long-term in Italy) four Reference and placed cough into Copan, National was and the aliquoted swab (UTM; [?]38degC to The then Medium fever [?]38 box was Transport 2018). of cold Universal fever al., history a of et of or in mL (Fitzner history fever immediately hospitalization) 3 (measured were or requiring with SARI days swabs influenza-like fever tube 10 or nasopharyngeal an (measured labelled last days) 3903 for the ILI 10 of within sites last for onset total the sentinel criteria with consultation a within other WHO for 2018, onset four the Complex with December to Paediatric cough meeting to or Bangui patients 2015 were the syndrome from January Samples From to (SARI) collected CAF. came illness syndrome. in who respiratory programme (ILI) age surveillance acute illness of influenza severe years national a the 5 for of under part children as from out collected carried was study This collection Sample CAF. sentinel in Methods 5 severity in disease recruited and not, seasonality or prevalence, aged hospitalized RSV children age, into of of insights years (10/329) first 5 3.0% provide under and in children sites from RSV 2010 strains December reported nt RSV to study characterised 60 January and preliminary a from a carry enrolled (CAF), years and 0-15 worldwide Republic circulating African corresponding RSV-B Central frequent sequence predominant In most gene the duplication the the become known in is now largest duplication have and the (nt) duplication protein, 1999, Canada nucleotide G in in the 72 detected 2010 of a first in the region contains BA1-BA14) described in C-terminal It and first the genotypes THB to was date. 37 genotype to JAB1, and ON1 genotype CBB, ON1) RSV-A the CB1, and sub-group, URU1-URU2, NA1-NA4, RSV-A SAB1-SAB4, CB-A, the B SAA1-SAA2, (GB1-GB13, and (GA1-GA7, sub-group A classified sub-group B have sub-groups protein RSV-A phylogenetic G the divergent the of in highly variability genetic two and into antigenic the complicates RSV on and studies life molecular and throughout Epidemiological re-infections allowing response, immune the development of vaccine evasion facilitates protein G fec rmr B40(’AGTWCTTAGGT-’ n 14 w einse PCRs semi-nested Two F164. and (5’-ATGATTWYCYTTTGAAGTGTTC-3’) ABG490 primer, each of M 18,19 . ° o 0sc 55 sec, 30 for C 11 . 22 21 DAsnhsswscridotuigteSprcitIIFrtSrn enzyme First-Strand III SuperScript the using out carried was synthesis cDNA . yln odtoswr sflos 50 follows: as were conditions Cycling . μ ° o 0sc 72 sec, 30 for C aohrnelsa apeaiutuigteQAm ia RNA Viral QIAamp the using aliquot sample swab nasopharyngeal L ° o i,adafia xeso t72 at extension final a and min, 1 for C 20 2 ee eaaye pdmooia n lncldata clinical and epidemiological analysed we Here, . μ a N oyeae(rmg,UA n 10 and USA) (Promega, polymerase DNA Taq L 3,12,13 ° o 0mn 94 min, 30 for C odt,teeae1 genotypes 15 are there date, To . 2,4 nRVB h Agenotypes, BA the RSV-B, In . ° o 5mnfollowed min 15 for C ° o 0min. 10 for C 22 . 14-17 ° and C In . Posted on Authorea 14 Aug 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. iiat eeol nlddi h td fe bann eblcnetfo h hl’ aet rlegal or parents envelope. child’s sealed were a the results in The from practitioner rights. consent medical privacy verbal regular patient Par- with child’s obtaining compliance the after 2002). strict to in study August sent experts pseudo-anonymised, the 5 of were composed Data in of committee 0277/MSPP/CAB/DGSPP/DMPM/SMEE included guardians. ethics (Decree only an Health by were approved of ticipants was Ministry CAF the in out from carried programme surveillance The considerations Ethical continuous for tests sum rank Mann-Whitney χ using identi- v12.5, SigmaPlot in variables, were performed were acid analyses protein Statistical amino any G is X analyses the where Statistical N-X-S/T, of on server occur part sites 4.0 (P). glycosylation proline NetOGlyc hypervariable (N)-linked and than nitrogen (S) and other serine and second on (http://www.cbs.dtu.dk/services/NetNGlyc) (T) occur sites server threonine the glycosylation (O)-linked 1.0 Oxygen in NetNGlyc (http://www.cbs.dtu.dk/services/NetOGlyc). using sites fied glycosylation Potential G the Ar- sites of AY333364, part Glycosylation hypervariable (BA9: second the strains prototype in RSV-B the variability and amino-acid from the im- Canada) those visualise code with AB470478, to protein. genetic compared used NA1: was were standard BioEdit Canada; sequences the gentina). JN257693, amino-acid using The sequences (ON1: amino-acid software. RSV-A into BioEdit translated in were plemented sequences nucleotide The v6.06. MEGA analysis in Amino-acid implemented nucleotide as best iterations The bootstrap site. 1000 per with substitutions v6.06 method nucleotide MEGA Likelihood of BLAST with Maximum number selected with the was as analysed model expressed substitution and are and 2.5) model (version Likelihood v7.2.5 software BioEdit in SeqScape implemented using generated ( were sequences Consensus xxx. to xxx numbers analysis accession Phylogenetic the under GenBank in deposited were sequences study Unique sequencer. capillary the QIAquick 3130 ABI in availability the an bp using Data on 645 purified Purified primers and then PCR protocol. pb manufacturer’s were corresponding the 585 the amplicons the to between using in These according sequenced band band Netherlands) were a bp the RSV-B. products Venlo, 450 with (QIAGEN, as a samples kit with typed Purification and Samples were PCR RSV-A gel. PCR as agarose semi-nested typed 1.5% second were a PCR on electrophoresis semi-nested by first separated were products (5’- PCR BG517 primer or (5’-GATCYCAAACCTCAAACCAC-3’) antisense AG655 F164 the and with primers sample TTYGTTCCCTGTAGTATATGTG-3’) each sense on performed then were http://www.ncbi.nlm.nih.gov.BLAST/ -etwt h ae correction. Yates the with 2-test χ -etfrctgrclvralso -etfrlwpootos dsrto eecluae with calculated were ratios Odds proportions. low for z-test or variables categorical for 2-test 23 vltoaydsacswr acltduigteMxmmComposite Maximum the using calculated were distances Evolutionary . o iiaiysace.Alsqecswr lge sn ClustalW using aligned were sequences All searches. similarity for ) 24 n sdt aclt h hlgntcteswt the with trees phylogenetic the calculate to used and , 3 22 . Posted on Authorea 14 Aug 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. n21 a infiatyhge oprdt 05(=.0) 06(=.0)ad21 (p=0.031). 2018 and Prevalence (p=0.002) 2). 2016 (Table (p=0.002), 2017 in 2015 10.6% to to compared 2015 in higher 6.4% significantly from was ranged 2017 and years in across varied rates detection RSV RSV of circulation Seasonal S2). (Table patients 5 in ainsadicue antiin aai n ogntlhatdsae hnmaue 58,oxygen (5/8), measured When for disease. reported 0-7 were heart catarrhalis from Co-morbidities congenital Moraxella ranged these days. and hospitalisation For were 0-9 malaria had and levels from malnutrition, (p=0.162). onset males) ranged saturation included observed death symptom six and was and between females, patients hospitalisation death delay two 4 until and months, (13.8%; delay infection 24 the 8 RSV while than which days between younger among association all died, patients no enrolled 8 but patients infection, the RSV of neg, a (p (1.5%) (RSV hospitalisation 58/3903 levels of total duration saturation In bronchopneumonia increased oxygen with or on associated bronchiolitis influence was was significant of and RSV a n=874) diagnosis children, had SaO a hospitalized RSV median with 3), In n=294, (Table children 3). pneumonia in Table to detected (p=0.752; compared frequently convulsion more or OR=2.62, (p=0.816) significantly 5.5%, lethargy vs (p=0.107), (13.3% iting patients hospitalized among (p detected frequently more p were cases positive deaths RSV related RSV and severity Disease was p (6.4%) (4.0-7.5%; females groups to age compared other all (9.5%) to males compared in positive detection p RSV RSV-B, and 1.53, increased 40 cases. (OR= cases the observed SARI cases, ILI Of (67.5%) from RSV-positive 2017. were 27/40 the in (33.5%) with Among cases 52/155 compared SARI samples, patients of sub-group, overrepresentation RSV-A ILI RSV-B an were 155 the 2). with the (32.5%) (Table to cases, Of 13/40 RSV (12.8%) SARI of 40 from typed. presence were and be (66.4%) sub-group the not 103/155 RSV-A for could RT-PCR the (37.5%) by to positive 117 belonged tested while (49.7%) were 155 patients cases, all these of Among sex (312/3903) and 8.0% total, age In with association and of detection years RSV 4 had older the months to across 6 compared and recruited distribution hospitalization 0 were sex necessitating between S1). cases and symptoms Table aged severe SARI age p=0.014; Children more the of sites. with in 16.5% (p study presenting children differences to between of variability little 3.8 risk Complex, some were increased between Paediatric was an Bangui There while there the care, but at centers. study, (56.1%) pediatric 4 the recruited recruited in mainly other mainly clinical were specialized were the cases and cases ILI is in SARI demographic that 0.9:1). centers. The of hospital sentinel the ratio 5 a male study. to collected of female: were the out corresponding samples (48.1%; 4 in nasopharyngeal patients syndrome more at female included Slightly than respiratory were 1. (51.9%) Table a male definitions in from given with case are patients patients (68.5%) enrolled 3903 for ILI characteristics 2018, or December (31.5%) to SARI 2015 January patients From of characteristics clinical and Demographic Results < < .0;Tbe3.RVwsascae ihdsna(p dyspnea with associated was RSV 3). Table 0.001; .0)adiaiiyt ed(=.0)btntwt hnrhe p093,daroa(=.8) vom- (p=0.983), diarrhoea (p=0.993), rhinorrhoea with not but (p=0.002) feed to inability and 0.001) < .0) hl eae a oe iko rsnigwt AIcmae oml (OR=0.84, male to compared SARI with presenting of risk lower a had females while 0.001), 2 =96% , < < tetccu pneumoniae Streptococcus 5.Bceilc-netoswith co-infections Bacterial 95%. .0;Tbe3.Cide gd06mnh 1.% a nicesdrs ob RSV be to risk increased an had (13.4%) months 0-6 aged Children 3). Table 0.001; vs S o,n6,mda SaO median n=64, pos, RSV n/rc-netoswt nunaAvrswr detected were virus A influenza with co-infections and/or 4 < .0;Tbe3). Table 0.001; tpyoocsaureus Staphylococcus < 2 .0) heig(p wheezing 0.001), 9% =.4;SaO p=0.049; =92%; < 0.001). , < ampiu influenzae Haemophilus 2 .0) hs indrawing chest 0.001), eesntdetermined, not levels , Posted on Authorea 14 Aug 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. nRVtp slts e -lcsltdst NTcd)apae ntedpiaeae taioacid amino at area duplicate the in appeared code) S3; strains. (NTT prototype fig. site S5). the N-glycosylated genotype, to (Fig. new NA1 of identical 273 a of were 245 isolates, position 302 S4) position B and type acid fig. 259 RSV amino genotype, In (position at ON1 sites of appeared N-glycosylated 318 code) other and (NTT 247 The site position N-glycosylated genotypes. new NA1 a of isolates isolates A CAF type among RSV sites Among glycosylation of patterns distinct showed sites O-glycosylated isolates. and N- T290N, potentials H287Y, of sites Analysis S285F, O-glycosylated S5). and (I281T, Fig. (T270I, N region codon; region potentials stop duplication duplication of Q313 Profile the the T312N, in from P306S, four E305K, downstream K218T, T254I), T302A, 11 (P216L, (S247P, S297P, region and E292K, region duplication were conserved D273N) the substitutions the L272P, from amino-acid in 22 upstream V271A, two five of total including K233I), conserved A sequences L223P, the BA9 L219P, in S4). studied six Fig. the and the region, S283F; T259I) in duplication in Y280H, G254R, observed mutations L274P, the observed L248I/F, Y273H, Eleven from T245I, were L265H, upstream (I243S, (E262K, S307P/F) strains. region T320A) region duplication T319N/I, ON1 Y304H, total the S311L, the V303A, A from L310P, downstream of P300L, S3). (E308K, six region six Y297H, (Fig. and studied AB470478 E295K, region the strain identified H290Y, duplication prototype were in L289F, the identified K305I) to E286G, were and compared (G284S, E292K substitutions genotype L282P, amino-acid NA1 N281Y, the 29 N268S, of of gene (D245N, sequences G study substitutions the amino-acid the in six of of region total hypervariable A second the in in diversity sequences Genetic 18 novel, to represented sequences (corresponding CAF strains Most were four strains unique transmission. only unique local 6 strains. Four suggested on unpublished other which years previously local S2). the cluster, clustered suggest two separate while Fig. might a sequences or 43.5%; which genotype, formed nucleotide 2017-2018 one total) (10/23, BA9 in identified unique over the and found were Twenty-six found within was observed sequences were (n=79) interspersed BA9 were S1). strains strains unique identical 29.4%) Ten same of for (Fig. (5/17, cluster transmission. The 0-6.3% 2017 large sequences a NA1, to NA1 21.7%). while RSV-A 2015 unique (26/120, occasions, for in Five genotype 0-1.4% found ON1 BA9. from was within RSV-B ranged strain 2016 for genotype same of same 0-6.4% the as the and NA1 of ON1 replaced strains RSV-A was ON1 between genotype genotype NA1 distances RSV-A RSV-A Genetic while 3). 120 88.2%) NA1, (Fig. (15/17, RSV-A identified 3). genotype 2015 were RSV-B 17 (Fig. in sequences or analyses BA9 detected phylogenetic RSV-A genotype on exclusively as RSV-B Based almost typed 23 sequences. successfully and gene samples ON1 G partial genotype positive 160 for in attempted resulted and was sequencing gene Glycoprotein in 2). Table predominant 3; was Fig. and 68.1%; analysis 2015-2017 (32/47, Phylogenetic 93.7%), in cases (30/32, detected RSV-positive 2015 was the in RSV-B of observed half was 100%). than the circulation (40/40, more RSV-A to 2018 representing high compared other 2016, and typed, season the be 92.1%) rainy during could (70/76, the than that in 2017 earlier strains detected months RSV p frequently 5 the 3.0%; more to Among 57/1892, significantly 3 vs also June, 12.7% was in cases (255/1756, and RSV of occurred season in number 1 incidence 2). dry higher peaked RSV significantly circulation (Fig. (Fig. a of RSV years to December peak and addition 3 until the In August 2017, lasted to (2018). in November March-April and reported or between March-April (2016) recorded in October were (2015), started detections September detections Sporadic RSV 2). period, Fig. study the During < 0.001). 5 Posted on Authorea 14 Aug 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. nCF hl A a h oiatgntp n21,isdtcinrtsdcesdadi a not was it and decreased rates documented detection well its is replacement 2015, genotype in temporal genotype RSV dominant 2018. the replacement in genotype was longer RSV-A any NA1 an found revealed While sequences, G CAF. glycoprotein in understand partial on better based country. countries to analyses, the between needed Phylogenetic in differs is duration that CAF and dominance in peak B surveillance was onset, and RSV-B RSV season (p=0.345), earlier RSV-A Long-term allowing 2018 of thus 2017. or seasons and periodicity in RSV-A (p=0.931) dominated the against circulation 2015 immunity RSV-B from RSV-A herd affecting differ than wider diversity. likely not longer and year, genetic did that lasted RSV in CAF subtype and/or and in predominant 2016 seasons earlier the in previous started incidence during seasons RSV in developed dominated Although earlier immunity RSV-A start as herd that China, of season outbreaks In incidence with level RSV year-cycle the disease the 2 by higher a of influenced with to start alternate linked earlier months start season 3-5 later an be the and peak Germany, to incidence a In lower tends with with higher average previously. seasons significantly the documented was D incidence to been the vitamin RSV have compared of where influence usual, CAF levels that than in lower radiation 2017 earlier to in UV due observed and winter as patterns, in temperature aerosols diseases humidity, of infectious stability relative and to as particles such viral of factors infectivity climatic Kenya in on as such depends climate, annual tropical significant climates circulation a with RSV temperate with 2015-2018, While countries 38 in of African fluctuations. winter season) period in dry the season the in in during 3.0% vs 8.0% high season of rainy is RSV in (12.7% of seasonal prevalence and overall (6.4%-10.6%) previously an infections. showed reported respiratory study already to Our as susceptibility 6.4%), in vs differences 29.6% (9.5% sex vs that system infection to showed (33.3% immune contribute RSV also the hospitalisation to analyses on to susceptible Our influence leading more CAF). Hormonal symptoms were in severe and (4.0-7.5% more female) incidence frequently in lower more with developed protection. albeit full patients response confer groups, immune male to age humoral enough older boost high in not then likely detected will are mother that titers the reinfections antibody of the allows but infants exposure This during decreased young RSV rates and in recent also infection — less response shown higher or group immune was shown more age birth by have of month elicited month reports 0–6 antibodies infections the Previous of the to primary rate according in old. to detection risk years linked 13.4% hospitalization the life 4-5 — had and of children birth months status, year in after 0-6 infection first 4.0% months aged to (RSV) to children first their due age, groups, the of infections, with age during regardless respiratory other high hospitalized the on was being to studies RSV of Compared surveillance risk system. in increased immune represented an their under often children of in more immaturity infections the usually respiratory severe are CAF and infants in mild of Young age cause of important an years is 5 RSV that showed study Our Discussion 0.5-0.7. O-glycosylated of potential score 77 a to with up of predicted residues score RSV-B threonine a of and strains with serine 7 O-glycosylated of predicted of be sites sites profile would acid and O-glycosylation amino O-glycosylated threonine The of and Analysis analyzed. serine and NA1) were protein for G protein sites genotype G 102 ON1 genotype and 0.5-0.7. the NA1 ON1 for CAF for sequences sites the acid (402 for amino acids 22 when amino similar 3 was profile O-glycosylation The loi A otcsswr eotdi oebri td rm2010 from study a in November in reported were cases most CAF in Also . 43,44 aeahge niec n nrae optlsto rates hospitalisation increased and incidence higher a have , 2,22,25 n stefis oepoei eal h pdmooyo S ntecountry. the in RSV of epidemiology the details in explore to first the is and 35 7,12,26-28 n/rara ntmcldifferences anatomical airway and/or 12 ihRVicdneuulycicdswt h rainy the with coincides usually incidence RSV high a , 39 ihntefis ero ie infiatdffrnein difference significant a life, of year first the Within . 6 rhs atr uha vrl nrae susceptibility increased overall as such factors host or 29 ikdt nataeadlvl fmaternal of levels and age infant to linked , 40-42 36 eitosfo vrl seasonality overall from Deviations . 30,31 Cameroon , 32,33 12 S neto ed ohumoral to leads infection RSV . 43 45-47 n xliigwyRVi still is RSV why explaining and nSizradadFinland, and Switzerland In . ubekproiiyi likely is periodicity Outbreak . n orfiedt nRSV on data refine to and , 20 31 S esnlt likely seasonality RSV . 37 Senegal , aebe rpsdto proposed been have 48-50 n sfacilitated is and 25 n Ghana and 31,34 45 . . Posted on Authorea 14 Aug 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. S ekicdne hudb osdrd oprn pdmooia aawt ete aamyprovide may data infections. weather RSV with of data of seasonality months epidemiological the 6 Comparing into within campaigns Given considered. born Awareness insight children be early additional infections. of genotypes. should and mothers RSV incidence, circulating target deadly awareness which peak and the vaccine, infection, RSV severe RSV licensed of preventing of for a impact manifestations options clinical for clinical concerning best waiting the the understand while remain assess care better molecular and to clinical to This costs and data administration ON1. multiyear CAF palivizumab to of in preventive NA1 comparisons patterns future from for replacement transmission reference genotype RSV RSV- a RSV-A and constitutes and RSV-A study of predominance circulation epidemiological alternating concomitant showed an CAF in with RSV B on study epidemiological in-depth first This future. the screening Conclusion in RT-PCR country real-time the in sensitive detection more RSV a of and sensitivity the criteria USA improve surveillance the will RSV approach in extended revised found were and combining rates ARI Therefore, detection (23%; Using similar Germany While definitions. RT-PCR. in case real-time SARI our using and identification of by (6.1%, case ILI improved limitation RSV greatly the a for be of sensitivity constituting can part increase surveillance, is should influenza definitions symptom SARI for this while developed fever, definitions develop case WHO of study use before the reported respiratory to as lower and feed upper potentially to both might of inability symptoms glycosylation include N-linked can 318-320 of and vary (positions infections strains) infections loss RSV BA9 or of 3 manifestations strains) Clinical in BA9 310-312 unique or 3 296-298 in antigenicity D273N strains, affect and ON1 NA1 unique unique 4 antibodies 3 in H287Y from in substitution substitution and evasion L274P (D245N I281T strain, RSV Gain S247P, prototype L223P, the the to substitutions to compared genotype-specific strains linked CAF been ON1 the has in observed substitutions polymorphism 33 help limited the will showed country. CAF CAF length, the in in in sequence detected circulation elimination the while genotype strain and are countries NA1 imported strains the neighbouring strains versus of While in local RSV number as of new the well importance that as concerning the maintain CAF characterize both suggesting may in to effort, re-introduction abroad, seasons, surveillance sequencing virus from Maintaining RSV the for country. strains main need increasing the RSV the the in with outside without introduced country outbreaks, interspersed season, also the two in strains dry between maintained the CAF were sustained population strains However, during the suggested these detected in 2017-2018 that transmission suggested cases (2016-2017 in also RSV seasons Sporadic strains 2018 consecutive and identical two time. 2016 during 79 in over identified of detected strains or cluster identical protein 2017-2018) of large or clusters G one Smaller the ON1, transmission. of Within local region CAF. hypervariable in continents second duplication different occurred the across the by predominant in conferred become advantage located have duplication They nt selection worldwide. 60 immune or and 72 evolution viral by 25 62 ned usata ubro S netdptet,epcal on infants young especially patients, infected RSV of number substantial a Indeed, . ri ey (8%; Kenya in or ) 60 norsuy S a infiatyascae ihdsna heig hs nrwn and indrawing chest wheezing, dyspnea, with associated significantly was RSV study, our In . 58,59 12 12 . n nGaa(23%; Ghana in and ) h N n A A tan hwdahge ereo oyopim Among polymorphism. of degree higher a showed strains CAF BA9 and ON1 the , 36 hnuigcnetoa TPR uhhge eeto ae eereported were rates detection higher much RT-PCR, conventional using when ) 26 hl t soito ihfvro og ol o easse due assessed be not could cough or fever with association its while , 53 nadto,tmoa tanrpaeetwti eoyealso genotype a within replacement strain temporal addition, In . 51 oal,RVAO1adRVBB eoye,wt a with genotypes, BA RSV-B and ON1 RSV-A Notably, . 38 ,we sn oesniiera-ieR-C assays RT-PCR real-time sensitive more using when ), 7 2 mn h 3mttosi A tan,the strains, BA9 in mutations 23 the Among . 56,57 eeas dnie nCFstrains. CAF in identified also were 26,61 2,4,19,38,50,52 14,55 oevr cenn efficiency screening Moreover, . oetal otiuigt its to contributing potentially ieydet fitness a to due likely , 4,19,50 aespread have , 26,61 onot do , 63 54 . . Posted on Authorea 14 Aug 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. iue hthv asdrpae netosi hlrnfo ua India. rural from children in infections repeated 665. caused have that viruses 11. glycoprotein. G virus syncytial respiratory City. Paulo Sao 10. in Bronchiolitis with systematic Infants a Hospitalized among 2015: in children young 9. in virus syncytial study. respiratory modelling to and due review meta-analysis. infections respiratory and lower review acute systematic a 8. children: young in 2016. 2010;375(9725):1545-1555. virus Study Disease syncytial of respiratory Burden Global the for 7. analysis systematic a Dis. Infect 1990-2016: Lancet countries, 195 in infections 6. virus. duplication. syncytial gene respiratory G of nucleotide 72 a with 5. genotype novel a Ontario: in culating Korea. 4. in 2014. children hospitalized during in Arabia (RSV) virus Saudi Riyadh, in 3. Strains (RSV) Virus Syncytial 2016;11(11):e0166145. Respiratory B Group 2. 1956;104(4):555-576. 1 Oct 1. References interests. of conflict no have they that declare authors The interest Luxembourg the of by Conflict funded fellowship MAE-IV training [grants Lux- PhD the Health a by of Affairs. by USA, European Institute supported of and Luxembourg also (DHHS) Foreign and R. was of Service Affairs and Ministry Komoyo Human Sausy G.F. and European A. Health MAE-V]. and Selekon, of Foreign and B. Department of CPB, the Ministry by the embourg supported from was samples study the This taking for Ngombi help. technical L. for thank Sinner to wish authors The Acknowledgments sah ,DvuiV,LiR ta.Gntcvraiiyo ua eprtr ycta iu tan cir- strains A virus syncytial respiratory human of variability Genetic al. et R, Lai VR, Duvvuri A, Eshaghi he ,Hie H ave ,e l oCruaino 2pDpiainGopAad6b Duplication 60bp and A Group Duplication 72bp of Co-Circulation al. et S, Parveen SH, Haider A, Ahmed agsiKA b lGayM as G esnA,Hl-aton A oeua epidemiology Molecular GA. Hill-Cawthorne AM, Kesson MG, Walsh M, Ghany El Abd KNA, Pangesti siae ftegoa,rgoa,adntoa obdt,mraiy n eilge flwrrespiratory lower of aetiologies and mortality, morbidity, national and regional, global, the of Estimates hnc M soito fanwtp fctptoei yoiu ihifniecroup. infantile with myxovirus cytopathogenic of type new a of Association RM. Chanock iiaS,Toael M ePui ,e l netosCue yHS N r Predominant Are ON1 A HRSV by Caused Infections al. et M, Paulis de LM, Thomazelli SE, Vieira akY,Co H ogM,e l rvlneadgntccaatrzto frsiaoysyncytial respiratory of characterization genetic and Prevalence al. et MS, Song EH, Choi YH, Baek h ,MAlse A ’re L ta.Goa,rgoa,adntoa ies udnetmtsof estimates burden disease national and regional, Global, al. et KL, O’Brien DA, McAllister T, Shi arH oe J ese D ta.Goa udno ct oe eprtr netosdeto due infections respiratory lower acute of burden Global al. et BD, Gessner DJ, Nokes H, Nair ave ,BorS aorS,Fwe ,SledrW.Gntcdvriyaogrsiaoysyncytial respiratory among diversity Genetic WM. Sullender K, Fowler SK, Kapoor S, Broor S, Parveen rp A oe P ansL,ZegH upyP,Adro J XCceoiemmcyby mimicry chemokine CX3C LJ. Anderson PM, Murphy H, Zheng LM, Haynes LP, Jones RA, Tripp o 2018;18(11):1191-1210. Nov Lancet. e e Virol. Med Rev e 2017;390(10098):946-958. 2 Sep a Immunol. Nat a 2018;28(2). Mar rhVirol. Arch 8 u 2001;2(8):732-738. Aug u 2012;157(6):1039-1050. Jun imdRsInt. Res Biomed e Virol. Med J LSOne. PLoS 2017:3459785. a 2006;78(5):659- May 2012;7(3):e32807. Lancet. x Med. Exp J LSOne. PLoS a 1 May Posted on Authorea 14 Aug 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. ycta iu optlzto ncide nnrhr Spain. northern in children in hospitalization virus syncytial Kenya. Dadaab, Camp, 29. Hagadera in Older and Years 2015;93(6):1371-1376. 5 Aged Refugees Among Ghana. in infection 28. tract respiratory lower acute for hospitalized surveillance virus syncytial respiratory 27. global WHO the from results pilot. definition-Interim 2012-2015. case Surveillance, of performance of Years Consecutive 26. Four after Senegal in 2016;11(6):e0157163. Virus Syncytial piratory 25. 6.0. version Analysis 24. 95/98/NT. 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South in seasons genotypes. consecutive B four and over virus syncytial respiratory 2007. 13. to 1998 from Germany in lating 12. oae A he A aaoN ta.Eilg n niec fVrlAueRsiaoyInfections Respiratory Acute Viral of Incidence and Etiology al. et N, Marano JA, Ahmed GA, Mohamed alT.Bodt srfinl ilgclsqec lgmn dtradaayi rga o Windows for program analysis and editor alignment sequence biological user-friendly a BioEdit: TA. Hall ave ,SledrW,Fwe ,LfoizE,Kpo K ro .Gntcvraiiyi h pro- G the in variability Genetic S. Broor SK, Kapoor EJ, Lefkowitz K, Fowler WM, Sullender S, Parveen e ,Xa ,Zo ,XaQ i .Mlclrcaatrzto fhmnrsiaoysnyilvirus syncytial respiratory human of characterization Molecular E. Liu Q, Xia L, Zhou Q, Xiao L, Ren he ,PrenS lHsia M lAeyS.A vriwo eprtr ycta iu infec- virus syncytial respiratory of overview An SF. Al-Amery SM, Al-Hassinah S, Parveen A, Ahmed iui ,Mrie-a ,Mrn-aarg ,Serssmg ,SleoB atlaJ Respiratory J. 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No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. rzn,2010-2014. Arizona, Brazil. 47. Southern in infections pediatric 2014;11:36. community-acquired 24 and nosocomial among genotypes 46. mariPOC(R) multianalyte Dis. and Infect automated an from 45. obtained 2014 and test. 2010 pathogen respiratory between Finland in infections 44. Switzerland. in epidemics virus 43. expression. gene peptide antimicrobial of 42. 456. 41. 2006;134(6):1129-1140. 40. virus. syncytial analysis, respiratory of epidemiological activity molecular A infection: 39. tract respiratory lower 2013-2014. acute and with 2006 Ghana from children epidemic in consecutive three during 38. 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Melero B, Garcia-Barreno FX, Real C, Franci I, Martinez R, Garcia-Beato a 2004;78(9):4675-4683. May Pediatr. J eiti netDsSoc. Dis Infect Pediatric J Virology. c Rep. Sci u 2005;41(3):345-351. 1 Aug o 03135Suppl):S112-117. 2003;143(5 Nov u 1988;164(2):458-466. Jun e 72019;9(1):20097. 27 Dec lnMicrobiol. Clin J e 52019;8(4):325-333. 25 Sep e 2010;48(9):3423-3427. Sep 11 netGntEvol. Genet Infect LSOne. PLoS Virol. J LSOne. PLoS netDis. Infect J 2014;9(10):e109191. u 2010;84(15):7500- Aug u 2018;60:140-150. Jun netDis. Infect J 2013;8(9):e75020. Virology. e 52013;208 15 Dec netDis. Infect J Virol. J u 15 Jul May Aug J Posted on Authorea 14 Aug 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. 088/08(.)2 64/1(94 /1(.)4/1(50.6) 41/81 (33.9) (26.6) 39/115 (0.0) (38.5) 17/64 0/81 20/52 (37.5) 117/312 (50.0) (12.8) (5.2) 32/64 40/312 6/115 (3.8) 2/52 0 typed Not 21 27 6 0 0 11 13 0 (49.4) (49.7) 40/81 155/312 2 (23.4) 15/64 (60.9) 70/115 103 (57.7) 16 30/52 9 64 14 52 RSV-B 24 6 6 16 (8.0) 312/3903 (7.8) 81/1038 Total (10.6) 115/1084 2018 (6.6) 64/968 2017 (6.4) 52/813 2016 2015 RSV-A detections RSV Total Year type 2: Table 1: Table Tables (n=195). counted are RSV-B or RSV-A as typed be could that strains 3 Fig. distinction 2 Fig. 1 Fig. legends Figure AI13(25 4 3.)48(41 2 2.)13 (31.5) (68.5) 1231 2672 (21.7) (78.3) 225 813 (24.7) 965 (44.1) (55.9) 478 (16.9) 606 660 (22.6) (35.6) 235 (64.4) 345 623 (22.6) (22.5) 235 879 (22.5) (77.5) 183 (22.3) 630 (14.8) (8.4) 242 579 327 (21.6) 224 (8.0) 87 (24.5) (15.8) 237 164 (29.0) (8.4) 314 (9.7) (13.3) 87 (30.9) 379 (21.0) 129 251 820 (21.9) (25.7) (8.6) 212 209 93 (10.3) (16.6) 107 (17.3) 646 180 (8.2) 89 (21.3) (15.9) 830 129 (17.9) (17.0) 173 663 (18.7) (27.1) (32.1) 194 1058 348 (8.4) (48.1) 91 (21.0) (18.3) (51.9) 1877 (9.0) 218 149 2026 87 (19.8) 206 (22.4) (15.7) (21.8) 217 170 226 (10.3) 100 (48.6) (22.0) SARI (51.4) 504 239 534 (7.9) (16.3) 64 177 (15.9) ILI (%) (29.3) 154 N (9.2) 318 (10.0) 75 case, 81 (22.3) (45.4) Clinical (54.6) 216 492 592 (15.5) (15.7) Joseph 150 128 Saint (27.0) 261 (19.3) 157 (51.9) Pissa (48.1) (16.0) 502 466 130 Complex (31.1) Paediatric 253 Bangui 3903) (46.6) Total (53.4) = 379 434 Bossemb´el´e (N Boali =1038) (N (%) N Sites, =1084) (N months 49-60 2018 968) months = 37-48 (N months 25-36 =813) (N months 13-24 2017 months 7-12 months 0-6 (%) N Age, Female 2016 Male (%) N Sex, number Total 2015 characteristics Demographic itiuino S ae ymnhoe h oryaso h study the of years four the over month by cases RSV of Distribution : atrso S- n S- eoyecruaini eta fia eulc 0521.Only 2015-2018. Republic, African Central in circulation genotype RSV-B and RSV-A of Patterns : vra fRVsaosoe h oryas(0521)o h td n vrl r/an season dry/rainy overall and study the of (2015-2018) years four the over seasons RSV of Overlap : / % / % / % / (%) n/N (%) n/N n n (%) n/N n n (%) n/N eorpi hrceitc fptet nlddi h td yyear by study the in included patients of characteristics Demographic itiuino h S u-rus(S- n S-)acrigt td eradsyndrome and year study to according RSV-B) and (RSV-A sub-groups RSV the of Distribution L AITtlIISR oa Total Total SARI ILI Total SARI ILI 12 Posted on Authorea 14 Aug 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. rnhoii 331(03 .2(.7-24)p=0.030 2.46) - (1.07 1.62 ref (20.3) 63/311 (13.6) 45/332 - p=0.006 5.63) - (1.32 2.79 - (30.4) 14/46 (7.7) 42/542 others or determined Not Bronchopneumonia others or determined Not Bronchiolitis admission* Bronchopneumonia upon Diagnosis Pneumonia admission* upon Diagnosis convulsion p 3.31) - ref (2.08 2.62 feed to inability (13.3) (5.5) 164/1231 148/2672 p p 0.48) - lethargy (0.15 0.27 p 0.61) - (0.24 0.38 p 0.56) - (0.26 p 0.38 p 0.58) (4.0) - vomiting 13/327 (0.30 0.74) 0.41 - 1.94) (5.5) (0.38 - 21/379 0.53 (1.21 1.53 (5.6) 36/646 ref (6.0) (9.5) ref diarrhoea 50/830 192/2026 (7.5) value 50/663 (6.4) p (13.4) 120/1877 142/1058 CI) (95% indrawing OR chest wheezing (%) n/N dyspnea rhinorrhoea symptoms Clinical SARI ILI case Clinical months 49-60 months 37-48 months 25-36 months 13-24 months 7-12 months 0-6 group Age M F Sex Variable detection RSV 3 Table S rvlnei hlrnadeauto fcaatrsisascae ihicesdod of odds increased with associated characteristics of evaluation and children in prevalence RSV : e 824(.)11 06 .5 p=0.752 1.85) - (0.68 1.12 ref p=0.002 (8.8) 18/204 2.27) - (7.9) (1.22 294/3699 p=0.816 1.66 2.82) ref - (0.16 0.68 (11.8) 54/456 (7.5) 258/3447 p=0.107 ref 1.74) (5.6) - 2/36 (0.96 (8.0) 1.29 310/3867 p=0.983 ref 1.30) (9.7) - 59/608 (0.76 (7.7) 0.99 253/3295 ref p yes (8.0) 74/930 3.24) no - (8.0) (1.69 238/2973 2.34 ref p yes (15.6) 50/321 4.47) no - (7.3) (2.61 262/3582 3.41 ref yes p (19.2) 88/459 no (6.5) 3.19) 224/3444 - (1.98 2.51 ref yes p=0.993 (14.1) 129/916 no (6.1) 1.48) 183/2987 - (0.65 ref 0.98 yes (8.0) 285/3571 no (8.1) 27/332 yes no yes no yes no yes no 13 < < < < < < < < < < 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 Posted on Authorea 14 Aug 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. central-african-republic-2015-to-2018 prevalence-and-severity-of-respiratory-syncytial-virus-infections-in-children-in- Fig2.eps Komoyo_Supplementary file Hosted central-african-republic-2015-to-2018 475456-prevalence-and-severity-of-respiratory-syncytial-virus-infections-in-children-in- Fig1(1).eps Komoyo_Supplementary file Hosted only children hospitalized for * vial at available vial at available https://authorea.com/users/350658/articles/475456- 14 https://authorea.com/users/350658/articles/ Posted on Authorea 14 Aug 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159741398.81741923 — This a preprint and has not been peer reviewed. Data may be preliminary. 15