Human rhinoviruses and Influenza

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1 Human rhinoviruses and Influenza 3 rd Annual ANISE Meeting at Crowne Plaza-Nairobi Clayton Onyango, PhD KEMRI-Wellcome Trust Programme, Kilifi

2 Paediatric IP respiratory virus surveillance at KDH 60 Multiplex Results 100 Cumulative No. of Viruses / Samples Tested Proportion Positive Week RSV Flu Parainfluenza Coronavirus Rhinovirus Adenovirus M. Pneumonia hmpv

3 Respiratory virus incidence KDH Incidence (/100,000/year) <1 yr <5 yr <13 yr Flu RSV Adeno PIV hcov HRV hmpv Virus

4 Age-distribution respiratory virus pneumonia admissions hmpv (128) 0.30 Rhino (550) 0.30 Adeno (131) Proportion of cases RSV (1195) Proportion of cases RSV Proportion of cases RSV hcorona (132) 0.30 Flu (125) 0.30 PIV (172) Proportion of cases RSV Proportion of cases RSV Proportion of cases RSV Age in months

5 Disease Association hmpv PIV Flu Adeno Odds ratio 30 0 % positive RSV HMPV PIV Flu Adeno hrhino Corona Well controls Pneumonia cases Series2

6 HRV by severity - KDH Severity category Species (%) Total HRV-A HRV-B HRV-C Non-ARI 8 (61.54) 1 (7.69) 4 (30.77) 13 URTI 6 (28.57) 4 (19.05) 11 (52.38) 21 Mild 18 (51.43) 2 (5.71) 15 (42.86) 35 Severe 96 (44.86) 7 (3.27) 111 (51.87) 214 V. Severe 27 (55.1) 4 (8.16) 18 (36.73) 49 Total 155 (46.69) 18 (5.42) 159 (47.89) 332

7 Co-infecting viruses Co-infections Total infect Virus n % n % n % RSV HRV Flu Coinfections / % vs pneumonia 0 1+ P (1 tail) RSV 52/419 12% 10/ % HRV 72/327 22% 10/ % Flu 18/72 25% 5/27 19% 0.347

8 Influenza 10 Flu C Flu B Flu A H1N1 8 No of Patients Week

9 Human rhinovirus (HRV) HRV is the primary causative agent of the common cold Studies suggest that HRV infection is associated with asthma and chronic obstructive pulmonary disease (Gwaltney et al., 1996, Nicholson et al., 1993, Johnston et al., 1996 and Varkey et al., 2008) Early HRV infection also appears to be a major risk factor for asthma in later life (Jackson et al., 2008) These lower airway effects represent significant morbidity and mortality associated with HRV

10 HRV capsid and viral classification Capsid proteins Non structural proteins HRV-A susceptible to WIN51711 HRV-B susceptible to chalone, dichloroflavin and R61837 VP1 genetic classification Recently, use of genetic sequences from the VP4/VP2 junction

11 HH 40: Rhinovirus Infection Patterns Mum 29 yo HH members B2 B1 S Start of home visits 9 yo 6 yo 2 yo Inf 1 mo 1 dec'09 1 jan 1 feb 1 mar 1 apr 1 may 1 jun'10 Legend Collected samples HRV positive Sample date

12 B2-04 Mum-04 Mum-04 B2-03 S-03 Inf-04 B2-04 Inf-04 Inf-05 S-04 S-04 B1-04 Inf-03 Inf-05 HRVAb HRVAc B1-10 B1-09 B1-11 B1-17* S-20 B2-07 B1-07 S-12 Inf-07 S-08 Inf-08 S-12 HRVAa Inf-52 Inf-53 HRVBc HRVBa HRVBb HRVCb HRVCc HRVCa B1-19 B2-18 Inf-18 S-18 Inf-18 B2-19 Inf-14 Mum-15 B2-13 B1-13 S-14 B1-12 S-14 B1-12 B HRV-A HRVA-1 HRVA-2 HRVA-3 HRV-B HRVB-1 HRVC-1 HRVC-2 HRV-C HRV species in HH 40

13 HRV HH40 infection patterns Mum B2 B1 S VL Ct values Inf Dec '09 Jan Feb Mar Apr May Jun '10 Sample date Key: HRV variants A1 A2 A3 A4 A5 B1 C1 C2 Untyped

14 HH 51: Rhinovirus Infection Patterns HH members Start of Home visits =>50y <50y <15y <5y VL Ct values dec'09 1 jan 1 feb 1 mar 1 apr 1 may 1 jun'10 HRV species/epitypes A1 A2 A3 A4 C1 C2 C3 C4 C5 C6 Un-typed

15 HRV HH5 infection patterns HH members Start of Home visits =>50y <50y <15y <5y VL Ct values dec'09 1 jan 1 feb 1 mar 1 apr 1 may 1 jun'10 Sample date HRV species/epitypes A1 A2 A3 A4 A5 A6 B1 C1 C2 C3 C4 C5 Untyped

16 HH 19: Rhinovirus Infection Patterns HH members Start of Home visits =>50y <50y <15y <5y VL Ct values dec'09 1 jan 1 feb 1 mar 1 apr 1 may 1 jun'10 HRV species/epitypes A1 A2 A3 B1 B2 C1 C2 C3 Un-typed

17 HH 34: Rhinovirus Infection Patterns HH members Start of Home visits <50y <15y <5y VL Ct values dec'09 1 jan 1 feb 1 mar 1 apr 1 may 1 jun'10 HRV species/epitypes A1 A2 A3 B1 B2 C1 Un-typed

18 Characteristics of household members HH5 HH19 HH34 HH40 HH51 Species-Epitype (N=31) Family size No. positive Prop. Positive(%) Median age-yrs (Range) ( ) ( ) ( ) ( ) ( )

19

20 HH51 HH34 HH19 HH40 HRV-A1 HRV-A2 HRV-A3 HRV-A4 HRV-A5 HRV-A6 HRV-A7 HRV-A8 HRV-A9 HRV-A10 HRV-A11 HH5 HRV-B1 HRV-B2 HRV-B3 1 dec'09 1 jan 1 feb 1 mar 1 apr 1 may 1 jun'10 Sample date HRV-C1 HRV-C2 HRV-C3 HRV-C4 HRV-C5 HRV-C6 HRV-C7 HRV-C8

21

22

23 Conclusions On average 8 (6-11) epitypes infect households over 6 month period - Up to 6 different infections per individual per house hold Multiple epitypes can infect subjects over relatively short periods, but do not cause re-infection Similar findings to those of a serological study by Monto et al., 1987 i.e. the Tecumseh virus watch Data from the 5 HHs, suggest multiplicity of epitypes in the Matsangoni area What seemed as prolonged viral shedding is actually due to the introduction of multiple species and epitypes Clear model of the involvement of molecular biology in epidemiology

24 Acknowledgements Prof. James Nokes Prof. Pat Cane Patience Kiyuka Patrick Munywoki Charles Agoti Moses Kiti Anne Ashitiva James Tuju VEC Lab staff ANISE meeting organizers Clinic staff

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