Maneig de les infeccions respiratòries per virus emergents. Antonella Francesca Simonetti Servicio de Enfermedades Infecciosas

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1 Maneig de les infeccions respiratòries per virus emergents Antonella Francesca Simonetti Servicio de Enfermedades Infecciosas

2 Virus respiratorios emergentes Enterovirus D68 MERS-CoV

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4 Enterovirus D68 EV D68 first isolated in 1962 in Berkeley, 4children with CAP. 26 cases were confirmed in USA between 1970 and Minor outbreaks of EV D68: 699 cases in Europe, Africa, and southeast Asia between 1970 to In 2014 a large-scale outbreak of EV D68 causing severe respiratory infection mainly in children was noted in the USA and Canada, with subsequent reports from other countries: 2287 cases published. Outbreak reported in Aug-Sept 2016 in Sweden: 74 cases, 44 (59%) children < 5 yrs

5 Xiang Z, Wang J, Semin Respir Crit Care Med 2016

6 Age EV68 positive (30.8%) (34.7%) (14.4%) >16 78 (20%) Total 389 Poelman R et al,ecdc Study, J Clin Vir 2015

7 Schuffenecker I et al., Euro Surveill 2016

8 Dyrdack Ret al., Euro Surveill 2016

9 Clinical presentation Halm-Hansen CC et al., Lancet Inf Dis; 2016

10 Schuffenecker I et al., Euro Surveill 2016

11 Schuffenecker I et al., Euro Surveill 2016

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13 EV-D68 isolated in Spain (2014 outbreak) Age Sex Sample material Underlying disease Symptoms ICU coinfection Outcome 69 yrs Male TA Bronchoaspiration Bronchorrea No Pseudomonas aeruginosa, Candida albicans, candida glabrata Discharge 1 month Female NPA Prematurity Rhinorrea No No Discharge 5 months Female NPA No Bronchiolitis Yes HPV-4, Branhamella catarrhalis Discharge 1 month Female NPA Prematurity Rhinorrea No No Discharge 59 years Female BAL Lung traslpant Decrease lung capacity No Pseudomonas aeruginosa, Granulicatella adiacens Discharge Gimferrer L et al, Enferm Infecc Microbiol Clin 2015

14 Underlying diseases In USA children at least 60/195 (31%) had underlying disorders: 6 (10%) asthma 4 (7%) recurrent wheezing 3 (5%) congenital pulmonary defect 4 (7%) malignancy In 14 European countries: at least 131/389 (34%) had underlying disease: 72 (19%) had underlying respiratory illnesses 26 (7%) were immunocompromised 33 (8%) had non-respiratory illnesses Halm-Hansen CC et al., Lancet Inf Dis; 2016

15 Severe disease for EV-D68 Admission to ICU and MV: % In USA 14 deaths (1% ) of cases reported. Acute flaccid paralysis: not yet been fully established 107 pediatric cases of acute flaccid paralysis related to EV-D68 have been reported in the USA in the autumn 2014 outbreak 2 cases in Norway, 1 case in France, and 25 cases in Colorado and California, of which 12 tested positive for EV-D outbreak Sweden: 3 cases. Halm-Hansen CC et al., Lancet Inf Dis; 2016

16 Treatment No treatment is available for EV-D68 3 antiviral drugs pleconaril, pocapavir, and vapendavir are being clinically tested for enteroviral infections. Fluoxetine also might inhibit the replication of EV-D68. Support treatment Halm-Hansen CC et al., Lancet Inf Dis; 2016

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18 A 60-yr-old Saudi man was admitted on June 13, 2012, with fever X 7 days, cough, expectoration, and shortness of breath; rx oseltamivir, levo, P/T, and micafungin. ICU admission and IMV. On June 24, he died of ARDS and ARF. A new betacoronavirus in lineage C; HCoV-EMC, along with other bat coronavirus Zaki AM. N Engl J Med 2012

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21 Arabi YM et al, NEJM 2017

22 Epidemiology 7:1 direct exposure to dromedaries during the preceding 2 weeks. Infection may be associated with occupational exposures to dromedaries. MERS-CoV seropositivity 15 times higher in shepherds and 23 times higher in slaughterhouse workers than the general population. The routes of transmission remain unclear: contact with infectious nasal or other bodily secretions, and/or consumption of raw dromedary products (milk, meat) Direct exposure to dromedaries has been documented in only 40% of primary cases. Arabi IM et al, NEJM 2017

23 Alhamlan FS et al, BMC Open 2016

24 45 patients in a tertiary care center South Korea from May to July 2015 Ko JH et al, J Infection2016

25 47 individuals from Saudi Arabia with lab-confirmed MERS-CoV were identified between Sep 1, 2012, and June 15, 2013; 60% case-fatality rate Assiri A. Lancet Infect Dis 2013

26 Imaging findings at presentations in Saudi patients with Middle East respiratory syndrome Assiri A. Lancet Infect Dis 2013

27 Meta-analysis of 25 published articles Matsuyama R et al, BMC Public Health 2016

28 45 patients in a tertiary care center South Korea from May to July 2015 Ko JH et al, J Infection2016

29 Arabi IM et al, NEJM 2017

30 23 cases of MERS-CoV in the eastern province of Saudi Arabia The median incubation period was 5.2 days 21 of 23 cases were acquired by person-to-person transmission - hemodialysis units - ICUs - in-patient units 15 patients died (65%) Among 217 household contacts and > than 200 HCW, MERS-CoV infection developed in 5 family members and in 2 HCW. Assiri A. N Engl J Med 2013

31 SOUTH KOREA 2015 OUTBREAK 186 cases 184 nosocomial transmission 25 cases health workers 5 cases: 80% of transmissions 144 cases: no transmissions 37 deaths (19%) Kim SW et al, CID 2017

32 Kim SW et al, CID 2017

33 Investigational Studies in Humans Treatment options MERS Data from randomized clinical trials are lacking. Retrospective observational reports of treatment with ribavirin and interferons do not indicate consistent clinical benefits A meta-analysis of observational studies of passive immunotherapy for SARS and severe influenza suggests a decrease in mortality with serum from convalescent patients Immunomodulatory Agents A retrospective analysis (SARS) suggests that glucocorticoids may be associated with mortality. Preclinical Studies with Licensed and Experimental Drugs Ribavirin: inhibitory effects in vitro. Promising results of ribavirin and interferon alfa-2b among rhesus macaques Marmosets treated with lopinavir ritonavir or interferon beta-1b had substantially lower morbidity and mortality. Various experimental polyclonal and monoclonal antibodies, peptide constructs, and polymerase inhibitors have been tested in animal models One placebo-controlled trial of interferon beta-1b and lopinavir ritonavir has recently begun (ClinicalTrials.gov number NCT ). Arabi IM et al, NEJM 2017

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35 Onset of respiratory symptoms by week, reported by 129 Hajj pilgrims from France during their stay in Saudi Arabia, October 2013 Influenza virus (7.8%) MERS-CoV (0%) Nougairede A. Emerg Infect Dis 2014

36 Hajj associated respiratory infections Meta-analysis of 32 studies: The viruses most commonly isolated from symptomatic patients during the Hajj by PCR were rhinovirus ( % prevalence), followed by influenza virus ( %) and non-mers coronaviruses ( %). MERS coronavirus: 0% (Gautret et al.) India: 977 pts (11%) with respiratory symptoms, 300 participate in the study. 0 patients tested positive for MERS-CoV; however, 33 (11%) tested positive for influenza viruses. (Koul et al). UK: 202 patients with respiratory symptoms. 0 patients had a MERS-CoV infection. A viral aetiology was detected in half (50.3%) of the cases, with rhinoviruses, influenza A (H1N1 and H3N2), and influenza B being most frequent. (Atabani et al).

37 Enterovirus D68 Outbreak in Prevalently in children. High morbidity rate. Respiratory failure, ICU admission. Association with acute flaccid paralysis? 30% of patients with underlying diseases. No specific treatment.

38 MERS-CoV 1905 case reported from 2012; 80% in Saudi Arabia. Zoonosis: camel and dromedaries to human transmission. High morbidity: respiratory failure, ICU admission, MV. 40% mortality. Nosocomial outbreaks. NO specific treatment. Important surveillance and control of in-hospital transmissions.

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