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Hospital outbreak of middle east respiratory syndrome

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MERS CoV

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Hospital outbreak of middle east respiratory syndrome

  1. 1. HOSPITAL OUTBREAK OF MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS JOSE SOCRATES “DEE” M. EVARDONE YEAR LEVEL I IM DEPARTMENT, CDUH
  2. 2. HOSPITAL OUTBREAK OF MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS AUGUST 1, 2013 VOL. 369 NO. 5 PAGES 407-416 ABDULLAH ASSIRI, M.D., ALLISON MCGEER, M.D., TRISH M. PERL, M.D., ET AL JOSE SOCRATES “DEE” M. EVARDONE YEAR LEVEL I IM DEPARTMENT, CDUH
  3. 3. Study Overview A novel coronavirus (MERS-CoV) is causing severe disease in the Middle East. In this report on a hospital outbreak of MERS-CoV infection, 23 confirmed cases and evidence of person-to-person transmission were identified. The median incubation period was 5.2 days.
  4. 4. Objectives: To be able to review about Coronaviruses, Basic Epidemiology To be able to understand about MERS Cov  1) Virology  2) Epidemiology  3) Case definitions  4) Clinical manifestations  5) Diagnosis  6) Treatment  7) Prevention  8) Outcomes  9) Travel Recommendations
  5. 5. Methods
  6. 6. • Setting: • The governorate of Al-Hasa, eastern Saudi Arabia • Serves a mixed urban and rural population of 1.1 million persons. • 1) Hospital A is a 150-bed general hospital in the largest urban area (Al- Hufuf). The dialysis unit, which cares for 43 patients in two shifts per day, is an open unit with 16 beds spaced 1.3 to 1.5 m apart. The intensive care unit (ICU) contains two open 6-bed bays. • 2)Hospitals B and C are also general hospitals in Al-Hufuf. Hospital D is a regional referral hospital located 160 km from Al-Hufuf. METHODS: • The governorate of Al-Hasa, eastern Saudi Arabia • Serves a mixed urban and rural population of 1.1 million persons. • Hospital A is a 150-bed general hospital in the largest urban area (Al- Hufuf). • The dialysis unit: 43 patients, 2 shifts/day, open unit with 16 beds spaced 1.3 to 1.5 m apart. • The ICU contains two open 6-bed bays. • Hospitals B and Hospital C are general hospitals in Al-Hufuf. • Hospital D is a regional referral hospital located 160 km from Al-Hufuf.
  7. 7. METHODS: Definitions: Confirmed case of MERS-CoV infection: 1) laboratory evidence of MERS-CoV 2) either fever and at least one respiratory symptom or two respiratory symptoms without another identifiable cause. Probable case of MERS-CoV infection: 1) if he or she was a household, family, or health care contact of a person with a confirmed case 2) if pneumonia developed without another confirmed cause 3) either laboratory testing for MERS-CoV was not performed or a single test was negative and no other specimens were available for testing.
  8. 8. METHODS: Definitions: The date of onset: • febrile patients: the first day of fever that persisted for more than 48 hours • afebrile patients: the first day of new cough or shortness of breath. Exposed patients: had any face-to-face contact with a symptomatic patient who had a confirmed or probable case, 1) Was in the same hospital room or ward as a symptomatic case patient >1hr 2) Moved into a bed vacated by a symptomatic case patient 3) Was being cared for by a health care worker who was also caring for a symptomatic case patient, or 4) Was sharing hospital equipment with a symptomatic case patient.
  9. 9. METHODS: • Laboratory Surveillance: • September 2012, the Saudi Arabian Ministry of Health requested that all patients with pneumonia requiring admission to the ICU be tested for MERS-CoV. • Throat-swab (Eurotubo, Deltalab), • sputum, • tracheal-aspirate, or • bronchoalveolar- lavage placed in viral transport medium (Vircell), stored at 28°C, and transported within 72 hours to the Ministry of Health regional reference laboratory in Jeddah, Saudi Arabia, where they were subjected to real-time reverse-transcriptase–polymerase- chain-reaction (RT-PCR) assays totest for MERS-CoV.20 • For all patients, the results of RT-PCR tests were confirmed by measuring cycle- threshold values for viral load.
  10. 10. METHODS: Identification of Clusters, Collection of Case Data, and Assessment of Exposure • Hospital A initiated active surveillance for pneumonia on April 20, 2013, and conducted a retrospective review of in-hospital deaths and cases of pneumonia from March 1 through April 19. • They also reviewed the medical charts of patients with confirmed MERS-CoV infection to identify symptoms, laboratory findings, and clinical course. The Ministry of Health interviewed household contacts of patients with confirmed MERS-CoV infection and followed them for 14 days after exposure.
  11. 11. METHODS: Identification of Clusters, Collection of Case Data, and Assessment of Exposure • Mapped confirmed and probable MERSCoV cases in time and in space within health care facilities. • For each case, we identified potential exposures, with the assumption that face-to-face contact or time spent in the same area conferred a greater risk than shared caregivers, which in turn conferred a greater risk than shared equipment. • No assumptions were made about incubation periods. • Three of the authors reviewed potential exposures independently; when more than one potential exposure was possible, • the most likely source of exposure was identified by consensus among those authors and an additional author. • The corresponding author vouches for the accuracy and completeness of the data.
  12. 12. METHODS: Sequencing and Phylogenetic Analysis: • Full-genome sequences were obtained from specimens from four patients (Patients I, J, K, and V)
  13. 13. METHODS: • Statistical Analysis: • They calculated empirical cumulative density functions of the incubation period and serial intervals by computing the cumulative fraction of all observations that fell below each observed value in the respective data sets. • They estimated the incubation period by identifying the earliest and latest time of possible exposure and the time of symptom onset for each case. • Treating these times as interval-censored estimates of the incubation period for each person, we fit a log-normal distribution to these data using maximum-likelihood techniques. • We then examined the robustness of our estimates with multiple definitions of onset and with the exclusion of particular cases.
  14. 14. METHODS: Statistical Analysis: They estimated the serial interval by identifying the times of symptom onset in the patient and in the person who transmitted the infection (infected–infector pairs) and then fitting a lognormal distribution to these interval-censored They estimated the medians and 5th and 95th percentiles of the incubation period and the serial interval using the quantiles of the lognormal distribution fit to each data
  15. 15. Results
  16. 16. RESULTS: • Description of the Outbreak April 1 and May 23, 2013, a total of 23 confirmed cases of human infection with MERSCoV were identified in the eastern province of Saudi Arabia
  17. 17. RESULTS: A: Illness in Patients at Hospital A 1) Community Introductions 2) Hemodialysis Unit 3) ICU 4) Medical Ward B: Illness in Staff Members at Hospital A C: Illness in Family Members D: Illness with Onset in Other health care facilities
  18. 18. RESULTS:
  19. 19. RESULTS: Demographic and Clinical Features
  20. 20. RESULTS: Demographic and Clinical Features • median time from the onset of symptoms to ICU admission = 5 days (range, 1 to 10) • median time to the need for mechanical ventilation = 7 days (range, 3 to 11) • median time to death = 11 days (range, 5 to 27)
  21. 21. RESULTS: Transmission, Incubation Period, and Serial Interval One patient transmitted the infection to seven persons, one patient transmitted the infection to three persons, and four patients transmitted the infection to two persons each. The incubation period of confirmed cases was 5.2 days (95% confidence interval [CI], 1.9 to 14.7); distributions that were fit to our observed data indicated that 95% of infected patients would have an onset of symptoms by day 12.4 (95% CI of 95th percentile, 7.3 to 17.5), whereas 5% would have an onset of symptoms by day 2.2 (95% CI of 5th percentile, 1.2 to 3.1). We estimated that the serial interval was 7.6 days (95% CI, 2.5 to 23.1) (Fig. 3). The distributions that were fit to our observed data indicate that the serial interval was less than 19.4 days in 95% of cases (95% CI of 95th percentile, 11.7 to 27.0) and less than 3.0 days in 5% of cases (95% CI of 5th percentile, 1.8 to 4.2).
  22. 22. RESULTS: Sequencing and Phylogenetic Analysis Phylogenetic analysis of the four MERS-CoV genomes showed that the viruses form a monophyletic clade with a bootstrap support of 100%
  23. 23. Discussion
  24. 24. LABORATORY-CONFIRMED MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS INFECTION, APRIL– MAY 2013.Characteristics Patients with confirmed cases (n=23) Male sex — no. (%) 17 (74) Age — yr Median 56 Range 24–94 Age ≥50 yr — no. (%) 17 (74) Age ≥65 yr — no. (%) 6 (26) Obesity — no./total no. (%)* 5/21 (24) Underlying Illness — no. (%) End-stage renal disease 12 (52) Diabetes mellitus 17 (74) Cardiac disease 9 (39) Lung disease, including asthma 10 (43) Immunosuppressive condition other than renal disease 0 Symptoms before presentation — no. (%) Fever 20 (87) Cough 20 (87) Shortness of breath 11 (48) Gastrointestinal symptoms Any 8 (35) Vomiting 4 (17) Diarrhea 5 (22)
  25. 25. LABORATORY-CONFIRMED MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS INFECTION, APRIL– MAY 2013. 0 39% 43% 52% 74% 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 Immunosuppressive condition other than renal disease Cardiac disease Lung disease, including asthma End Stage Renal Disease Diabetes mellitus Underlying Illness Underlying Illness
  26. 26. LABORATORY-CONFIRMED MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS INFECTION, APRIL– MAY 2013.Characteristics Patients with confirmed cases (n=23) Male sex — no. (%) 17 (74) Age — yr Median 56 Range 24–94 Age ≥50 yr — no. (%) 17 (74) Age ≥65 yr — no. (%) 6 (26) Obesity — no./total no. (%)* 5/21 (24) Underlying Illness — no. (%) End-stage renal disease 12 (52) Diabetes mellitus 17 (74) Cardiac disease 9 (39) Lung disease, including asthma 10 (43) Immunosuppressive condition other than renal disease 0 Symptoms before presentation — no. (%) Fever 20 (87) Cough 20 (87) Shortness of breath 11 (48) Gastrointestinal symptoms Any 8 (35) Vomiting 4 (17) Diarrhea 5 (22)
  27. 27. TABLE 1. CHARACTERISTICS AND SYMPTOMS OF PATIENTS WITH LABORATORY-CONFIRMED MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS INFECTION, APRIL– MAY 2013. 17% 22% 35% 48% 87% 87% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% GI {Vomiting} (4) GI {Diarrhea} (5) GI {Any} (8) Shortness of breath (11) Fever (20) Cough (20) Symptoms before presentation GI {Vomiting} (4) GI {Diarrhea} (5) GI {Any} (8) Shortness of breath (11) Fever (20) Cough (20)
  28. 28. TABLE 1. CHARACTERISTICS AND SYMPTOMS OF PATIENTS WITH LABORATORY-CONFIRMED MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS INFECTION, APRIL– MAY 2013. (CONT..)Characteristics Patients with confirmed cases (n=23) Laboratory testing at presentation — no./total no. (%) Abnormal white-cell count† 5/23 (22) Abnormal platelet count‡ 5/23 (22) Elevated aspartate aminotransferase 3/13 (23) Oxygen saturation <95% while breathing ambient air 7/23 (30) Chest radiographic findings at presentation — no. (%) Normal 3 (13) Increased bronchovascular markings 4 (17) Unilateral infiltrate 10 (43) Bilateral infiltrates 5 (22) Diffuse reticulonodular pattern 1 (4) Clinical course — no. (%) Admitted to hospital 22 (96) Admitted to intensive care unit 18 (78) Received mechanical ventilation 18 (78) Outcome as of June 12, 2013 — no. (%) Recovered 6 (26) Remained in hospital§ 2 (9) Died 15 (65)
  29. 29. DISCUSSION: • Acute viral respiratory tract infections cause considerable morbidity and mortality and pose a risk of outbreaks in health care settings. • We describe a cluster of MERS-CoV infections and report health care–associated human-to-human transmission of MERS-CoV. The 65% case fatality rate in this outbreak is of concern.
  30. 30. DISCUSSION:
  31. 31. DISCUSSION:
  32. 32. DISCUSSION:
  33. 33. Conclusions
  34. 34. Conclusions • Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. • Surveillance and infection-control measures are critical to a global public health response.
  35. 35. EPIDEMIOLOGY Occurrence of infectious diseases: Sporadic - refers to a disease that occurs infrequently and irregularly Endemic - refers to the constant presence and/or usual prevalence of a disease or infectious agent in a population within a geographic area Hyperendemic - refers to persistent, high levels of disease occurrence. Epidemic - refers to an increase, often sudden, in the number of cases of a disease above what is normally expected in that population in that area. Principles of Epidemiology in Public Health Practice, 3rd Edition
  36. 36. EPIDEMIOLOGY Occurrence of infectious diseases: Outbreak- definition of epidemic, but is often used for a more limited geographic area Cluster - an aggregation of cases grouped in place and time that are suspected to be greater than the number expected, even though the expected number may not be known Pandemic - an epidemic that has spread over several countries or continents, usually affecting a large number of people. Principles of Epidemiology in Public Health Practice, 3rd Edition
  37. 37. EPIDEMIOLOGY Outbreaks Definition • Two or more people who experience a similar illness or confirmed infection, and are linked by a common factor, or • When the observed number of cases unaccountably exceeds the expected number for a given place and time. The terms epidemic and outbreak are used interchangeably. Principles of Epidemiology in Public Health Practice, 3rd Edition
  38. 38. EPIDEMIOLOGY Surveillance the continuing scrutiny of all aspects of the occurrence and spread of a disease that are pertinent to effective control. It involves a systematic collection, collation and analysis of data and the prompt dissemination of the resulting information to those who need to know so that action can result Principles of Epidemiology in Public Health Practice, 3rd Edition
  39. 39. CORONAVIRUS
  40. 40. CORONAVIRUS VIROLOGY Coronaviruses are members of the Nidovirus family, viruses that replicate using a nested set of mRNAs (“nido-” for “nest”). The human coronaviruses are classified in two genera: 1) alpha coronaviruses (HCoV-229E and HCoV-NL63) and 2) beta coronaviruses (HCoV-HKU1, HCoV-OC43), a) Middle East respiratory syndrome coronavirus [MERS-CoV], and b) Severe acute respiratory syndrome coronavirus [SARS-CoV]).
  41. 41. CORONAVIRUS • Viral composition — • medium-sized, enveloped, positive-stranded RNA viruses • name derives from their characteristic crown-like appearance in electron micrographs • These viruses have the largest known viral RNA genomes, with a length of 27 to 32 kb. • The host-derived membrane is studded with glycoprotein spikes and surrounds the genome, which is encased in a nucleocapsid that is helical in its relaxed form but assumes a roughly spherical shape in the virus particle
  42. 42. Phylogenetic relationships among members of the subfamily Coronavirinae and taxonomic position of MERS-CoV. de Groot R J et al. J. Virol. 2013;87:7790-7792
  43. 43. CORONAVIRUS VIRAL COMPOSITION • —
  44. 44. CORONAVIRUSWhat is coronavirus?
  45. 45. NOVEL HUMAN CORONAVIRUSES 1) Human coronavirus 229E 2) Human coronavirus OC43 3) SARS-CoV (2003) 4) Human Coronavirus NL63 (HCoV-NL63, New Haven coronavirus) (2003) 5) Human coronavirus HKU1 (2005) 6) Middle East respiratory syndrome coronavirus (MERS-CoV), previously known as Novel coronavirus 2012 and HCoV-EMC(2012)
  46. 46. CORONAVIRUS What is MERS? Middle East Respiratory Syndrome (MERS) -a viral respiratory illness -caused by a coronavirus called “Middle East Respiratory Syndrome Coronavirus” (MERS- CoV).
  47. 47. MERS-COV • Q: What are the symptoms of MERS? • severe acute respiratory illness with symptoms of fever, cough, and shortness of breath. • About half of them died. • Some people were reported as having a mild respiratory illness.
  48. 48. MERS-COV Genetic analysis—sufficient heterogeneity to support multiple separate animal-to-human transfers Cotten M, Watson SJ, Kellam P, et al. Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. Lancet 2013; 382:1993.
  49. 49. Saudi Arabia United Kingdom France Italy Tunisia Jordan Qatar United Arab Emirates Oman Malaysia United States
  50. 50. MERS-COV 1) “Index Patient” June 2012 KSA 2) Sept 2012, Qatar 3) Infected with no Epidemiologic link 4) Oct & Nov 2012 4 Men in 1 Family, Riyadh 2 died 5) Jordan 2 confirmed cases 6) January 2013, U.K. 7) Feb 2013, Px’s son 8) Family member 9) March 2013, Abu Dhabi, UAE 10) April 2013 23 confirmed cases 11 probable cases 11) May 2013, France 2 diagnosed 12) May 2013, Tunisia 3 cases 13) May 2013, Italy 3 cases
  51. 51. MERS-COV Possible sources and modes of transmission: 1) Bats 2) Camels 3) Human-to-Human
  52. 52. MERS-COV • Possible sources and modes of transmission: BATS • Bat Coronavirus RNA sequence closely related to MERS-CoV sequences • Might be a reservoir of MERS-CoV • unlikely that they are the immediate source
  53. 53. MERS-COV • Possible sources and modes of transmission: CAMELS
  54. 54. MERS-COV Possible sources and modes of transmission: CAMELS • Intermediate Hosts • viruses were quite similar and shared several unusual single nucleotide polymorphism • Attempts to isolate viruses were unsuccessful • Serologic studies have also suggested that camels are an important source of MERS-CoV • Using stored serum samples from 1992 to 2010, antibodies to MERS-CoV were detected as early as 1992 • 651 serum samples from dromedary camels (151 from 2003; 500 from 2013), 632 samples (97 percent) had antibodies against MERS-CoV, including all of the samples collected in 2003, prior to the outbreak in humans
  55. 55. MERS-COV What is the significance of the recent finding of MERS-CoV in a camel? The critical questions are : • What is the route by which humans are infected? • In what way are they exposed? Most patients who have tested positive for MERS-CoV • had neither a human source of infection • nor direct exposure to animals, including camels It is still unclear whether camels, even if infected with MERS-CoV, play a role in transmission to humans.
  56. 56. MERS-COV • Possible sources and modes of transmission: • Human-to-human transmission
  57. 57. MERS-COV • Possible sources and modes of transmission: • Human-to-human transmission
  58. 58. REVISED INTERIM CASE DEFINITION FOR REPORTING TO WHO AS OF 3 JULY 2013 CASE DEFINITIONS Confirmed case: A person with laboratory confirmation of infection with MERS-CoV Probable case:  A person with an acute respiratory infection (with or without fever) with clinical, radiographic, or histopathologic evidence of pulmonary parenchymal disease  No possibility of laboratory confirmation for MERS-CoV because either the patient or samples are not available for testing and  Close contact with a laboratory-confirmed case.
  59. 59. REVISED INTERIM CASE DEFINITION FOR REPORTING TO WHO (AS OF 3 JULY 2013) PROBABLE CASE CLINICAL LABORATORY EPIDEMIOLOGICAL acute febrile respiratory illness with clinical, radiological, or histopathological evidence of pulmonary parenchymal disease MERS-CoV is unavailable or negative on a single inadequate specimen direct epidemiologic-link with a confirmed MERS-CoV case acute febrile respiratory illness with clinical, radiological, or histopathological evidence of pulmonary parenchymal disease inconclusive MERS-CoV laboratory test direct epidemiologic-link with a confirmed MERS-CoV case acute febrile respiratory illness of any severity inconclusive MERS-CoV laboratory test resident of or traveler to Middle Eastern countries where MERS-CoV virus is believed to be circulating in the 14 days before onset of illness
  60. 60. CLINICAL MANIFESTATIONS • Incubation period - 5.2 days (1.9-14.7 days) • Clinical features : • 1) severely ill with pneumonia and acute respiratory distress syndrome • 2) some have had acute kidney injury
  61. 61. CORONAVIRUS 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 100% 98% 87% 83% 72% 32% 26% 21% 21% 17% 17% CLINICAL PICTURE
  62. 62. MERS-COV LABORATORY ABNORMALITIES — AMONG 47 CASES OF MERS-COV INFECTION IN SAUDI ARABIA 11% 11% 14% 15% 34% 36% 49% 0% 10% 20% 30% 40% 50% 60% Elevated ALT Lymphocytosis Leukopenia Elevated AST Lymphopenia Thrombocytopenia Elevated LDH .
  63. 63. MERS-COV Diagnosis 1) Polymerase chain reaction and sequencing -real-time reverse-transcriptase polymerase chain reaction (rRT- PCR) testing 2) Serology
  64. 64. MERS-COV DIAGNOSIS rRT-PCR - real-time reverse-transcriptase polymerase chain reaction Lower respiratory tract specimens Serum samples
  65. 65. MERS-COV DIAGNOSIS rRT-PCR Recommendations by WHO and CDC: 1) Lower respiratory tract specimens 2) Combined nasopharyngeal and oropharyngeal swab specimen 3) Acute and convalescent 4) blood, urine, and stool (uncertain) 5) Continued sampling and testing by rRT-PCR is encouraged 6) Nucleic acid sequencing in certain cases
  66. 66. MERS-COV DIAGNOSIS rRT-PCR • false-negative results • specimen was of poor quality, • collected late or very early in the illness, • not handled and shipped appropriately, and • technical problems with the test. • Three rRT-PCR assays for routine detection of MERS-CoV have been developed
  67. 67. MERS-COV DIAGNOSIS SEROLOGY • Detection of MERS-CoV Antibodies: • immunofluorescence assays • protein microarray assay • 2-stage approach by CDC • Screening: enzyme-linked immunosorbent assay (ELISA) • Confirmation: indirect immunofluorescence test or microneutralization test
  68. 68. MERS-COV Treatment NO antiviral agents are recommended for the treatment of MERS-CoV infection. 1) combination therapy with a)Interferon (IFN)-alpha-2b and b) Ribavirin appears promising None of the patients responded to therapy and all died of their illness. 2) Convalescent plasma, 3) Monoclonal antibodies, and 4) Inhibition of the main viral protease
  69. 69. MERS-COV OUTCOMES April 26, 2014 261 36% (93) Laboratory Confirmed Died Overestimate 14 19 (74%) Routine Surveillance 5 24 (21%) Secondary Cases AGE(47 patients) 39% (<50 yo) 48% (<60 yo) 75% (>60 yo)
  70. 70. MERS-COV TRAVEL RECOMMENDATIONS The Ministry of Health of Saudi Arabia recommended that in 2013, the following individuals postpone their plans to travel to Mecca, Saudi Arabia, for Hajj and/or Umrah due to the outbreak of MERS-CoV ●Elderly individuals (>65 years of age) ●Individuals with chronic diseases (eg, heart disease, kidney disease, respiratory disease, diabetes) ●Individuals with immunodeficiency (congenital or acquired) ●Patients with malignancy ●Patients with a terminal illness ●Pregnant women ●Children (<12 years of age)
  71. 71. THANK YOU

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