1. Middle East Respiratory Syndrome (MERS-COV) Done by : Fatimah Al-Shehri Intern pharmacist Supervised by : Dr . SahalKhoshhal Infectious disease clinical pharmacy specialist

7. Outline: • Case review . • Definition • Signs and symptoms • Transmission pathway • Epidemiology • Complications • Treatment. • Case follow up . • Prevention and control.

8. Case review : • 28 years old male admitted to the hospital on 30/3/2014 complaining of productive cough , generalized body pain , nausea , vomiting , sever headache, high grade fever, dysphasia and sever respiratory failure . • PMH: • Hx of glucose 6 phosphate deficiency (G6PD) . • Mild sulpha drugs allergy . • Medically free. • The patient is an orthopedic resident and he has a history of working in environment (KFH ) in which CORONA virus was detected. • After admission: • pneumonia was suspected since the X-ray was done that day and showed right middle zone infiltration and right middle lob pneumonia but then PCR was done and the viral DNA of CORONA VIRUS was extracted from the patient’s plasma so MERS-coV was confirmed . • The patient developed acute kidney injury , rhabdomyolysis , sever respiratory distress ,liver injury , increase in cardiac enzymes .

9. X-ray on 3/4/2014 FINDINGS: Examination compared with 28 March 2014. Interval development of bilateral air-space disease involving both middle lungs and the left lower lung likely related to chest infection, for clinical correlation and follow-up..

10. X-ray 4/4/2014 . FINDINGS: -Comparison was made to the previous study done yesterday. -Appearance of airspace opacity is noted in the middle zone of the right lung and middle zone of left lung.

11. X-ray16/4/2014 • FINDINGS: • -Comparison was made to the previous study dated April 16, 2014. • Redemonstration of the previously seen bilateral diffuse scattered consolidation with better aeration of both lungs. • -Bilateral interval decrease of pleural effusion. • Tubes and lines are noted in satisfactory position.

12. The laboratory value and vital signs since confirmation of MERS COV :

13. The laboratory value and vital signs since confirmation of MERS COV :

14. The laboratory value and vital signs since confirmation of MERS COV :

15. Medications:

16. CORONAVIRUSIS : • MERS (middle east respiratory syndrome): It’s a viral respiratory illness first reported in Saudi Arabia in 2012. • SARS ( Severe acute respiratory syndrome): It’s caused by a virus that was first identified in 2003. It causes acute respiratory distress and sometimes death.

17. Signs and symptoms : • Fever • Cough • Sneezing • Shortness of breath • Generalized body pain • Vomiting • Mayalgia

18. Transmission pathway:

19. Viruses classification

20. Classification of corona viruses:

21. Distribution of cases of MERS-CoV reported worldwide by month of disease onset, outcome and place of infection, as of 14 May 2013.

22. Distribution of cases of MERS-CoV by gender and age, April 2012 – 13 May 2013.

23. MERS- coV cases in KSA June 2012-June2013

24. Cases of MERS-CoV reported in the Arabian Peninsula and Jordan, April 2012 to 15 May 2013 .

25. Distribution of confirmed cases of MERS-CoVbyreporting country, 1 – 30 April 2014 .

26. Distribution of confirmed cases of MERS-CoV by age and sex, March 2012 – 31 March 2014 (n=206*) and 01 April - 30 April 2014.

27. Distribution of confirmed cases of MERS-CoV by month of onset* and place of reporting, March 2012 – 30 April 2014 .

28. Distribution of confirmed cases of MERS-CoV by reporting country, March 2012 – 30 April 2014 (n=424)

29. - Middle East:-Saudi Arabia: 342 cases / 105 deaths-UAE: 49 cases / 9 deaths-Qatar: 7 cases / 4 deaths-Jordan: 5 cases / 3 deaths-Oman: 2 cases / 2 deaths-Kuwait: 3 cases / 1 death-Egypt: 1 case/ 0 deaths Europe: -UK: 4 cases / 3 deaths-Germany: 2 cases / 1 death-France: 2 cases / 1 death-Italy: 1 case / 0 deaths-Greece: 1 case/ 0 deaths Africa:-Tunisia: 3 cases / 1 death

30. Complications: • Multi-organ damage .

31. Treatment:

32. Treatment : • Supportive care . • Chloroquine: • which has potent antiviral activity against the SARS-CoV (HCoV-229E and against HCoV-OC43 both in cultured cells and in a mouse model).

33. Treatment: • Respiratory aids. • Antivirals . • Patients in ICU (FAST HUG MAIDENS). • Monitoring of the kidney, liver, heart functions. • Monitoring of myoglobin ??

34. Respiratory aids: • Mechanical ventilation . • ECMO.

35. ECMO: Extracorporeal membrane oxygenation Indications: • Respiratory distress syndrome. • Primary pulmonary hypertension in newborn. • Congenital diaphragmatic hernia(CDH).

36. Antivirals : • Ribavirin : Antihepaciviral, Nucleoside (Anti-HCV) • Mechanism of action:

37. Ribavirin

38. Ribavirin • Doses : - Recommended therapy duration: - Genotype 1: 48 weeks. - Genotypes 2,3: 24 weeks. - <66 kg: 800 mg daily (400 mg in the morning and evening) - 66-80 kg: 1000 mg daily (400 mg in the morning, 600 mg in the evening) - 81-105 kg: 1200 mg daily (600 mg in the morning, 600 mg in the evening) - >105 kg: 1400 mg daily (600 mg in the morning, 800 mg in the evening).

39. Ribavirin • Ribavirin : • 2000 mg as loading dose then: • 1200mg q 8 hrs for 4 days . • 600 mg po q 8hrs for 4-6 days . • Peginterferon : • 1.5 mg/kg once /w for 2 doses.

40. Ribavirin: • Use : • Treatment of hospitalized infants and young children with respiratory syncytial virus (RSV) specially indicated for treatment of severe lower respiratory tract RSV infections in patients with an underlying compromising condition. - In combination with interferon alfa 2b (pegylated or nonpegylated) injection for the treatment of chronic hepatitis C . • Use - Unlabeled: - Treatment for RSV in adult hematopoietic stem cell or heart/lung transplant recipients. - Used in other viral infections including influenza A and B and adenovirus.

41. Interferon alpha: Interferons (IFNs):   proteins made and released by host cells in response to the presence of pathogens such as viruses ,bacteria, parasites or tumor cells.

42. Interferon alpha: Mechanism of action :

43. Treatment:

44. Replication of novel human corona virus hCoV-EMC/2012 in response to combined treatment with interferon alpha and Ribavirin in vetro cells.

48. Results :

49. Effects of (a) mycophenolic acid, (b) ribavirin, and (c) interferons (Intron A, Avonex, Rebif, and Betaferon) on MERS-CoV replication in Vero cells.

50. Effects of (a) mycophenolic acid, (b) ribavirin, and (c) interferons (Intron A, Avonex, Rebif, and Betaferon) on MERS-CoV replication in Vero cells.