This document summarizes the radiological and CT findings from a study of 13 patients in Mexico diagnosed with H1N1/09 influenza between March 2009 and March 2010. The most common patterns observed on CT were interstitial changes and consolidations appearing as ground-glass opacities or nodules, distributed bilaterally and predominantly in the basal regions of the lungs in a multifocal or diffuse manner. Younger patients were more likely to show no abnormalities on initial chest x-rays. Follow-up imaging in some patients demonstrated progression of disease within 24-48 hours.

1. PandemicMexican H1N1/09 Influenzae: Radiological & CT findings. This presentation participated in the last RSNA meeting

2. PandemicMexican H1N1/09 Influenzae: Radiological & CT findings. Gaspar-Alberto Motta-Ramírez, MD gamottar@ yahoo.com.mx Erika Alonso-Blancas, MD eri_alo_bla@hotmail.com Carlos Rodríguez-Treviño & José-Luis Ramírez-Arias, MD Departamento de Radiología e Imagen Hospital Ángeles del Pedregal. México City, MEXICO.

3. INTRODUCTION HA PB2 = Avian polymerase PB1 = Avian or human polymerase PA = Avian polymerase HA = Human or swine origin NP = Swine origin NA = Human or swine origin M – NS =Swine origin NA* = neuraminidase (binds to receptors on host cells) HA = hemagglutinin (helps initiate infection NA* PB2 PB1 PA HA NP NA M NS Viral Characteristics: In April 2009, the Mexican Secretariat of Health reported an outbreak of respiratory disease. In the affected patients, a novel swine origin influenza A (H1N1) virus (S-OIV) with molecular features of North American and Eurasian swine, avian, and human influenza viruses was found. Belongs to the genus orthomyxovirus under the family orthomyxoviridae, the genome consists of RNA molecules by single-stranded divided into eight segments. Thanks to replicate RNA polymerase consists of three subunits (PA, PB1 AND PB2), in surface sample virus hemagglutinin (HA) and amneuroaminidasa (NA). N Engl J Med. 2009 Jul 9;361(2):115-9. N Engl J Med 2010; May 362:1708-1719..

4. INTRODUCTION POST PANDEMIC PHASE 4 POST PEAK PHASE 5-6 PHASE 1-3 SUSTAINED HUMAN TO HUMAN TRANSMISSION POSSIBILITY OF RECURRENT EVENTS WIDESPREAD HUMAN INFECTION PREDOMINANTLY ANIMAL INFECTIONS:FEW HUMAN INFECTIONS DISEASE ACTIVITY AT SEASONAL LEVEL Epidemiology: In the same month, the World Health Organization (WHO) classified the global spread of this virus as a public health event of international concern. After documentation of human to human transmission of the virus in at least three countries of two WHO regions, The World Health Organization (WHO) has raised the level of influenza pandemic alert from phase 5 to phase 6 since June 11, 2009. Engl J Med. 2009 Aug 13;361(7):728-9.. and http://healthmap.org/en/es.php

5. INTRODUCTION Figure 1. Distribution of Reports of Cases of H1N1 Influenza. Data were collected by HealthMap during the first wave of the 2009 epidemic (April 1 through August 29, 2009) and were classified according to World Health Organization (WHO) phase. N Engl J Med 2010; May 6 362:1708-1719.

7. INTRODUCTION Figure 2a Figure 2c Figure 2b Figures 2 a-c Physicalbarriers Physical barriers to prevent the spread of the virus were: washing hands, use of mask, and isolation of potentially infected patients admitted primarily, these physical barriers were effective in preventing the spread of the virus. (figures 2 a-b) BMJ 2009; 339:367 and http://portal.salud.gob.mx /

8. EVALUATION. Unilateral Multifocal Bilateral Diffuse Consolidated Interstitial Figure 3 Unifocal Pleural fluid We performed a retrospective, descriptive analysis of the findings observed by radiography & thoracic CT with a lower respiratory tract illness initially classified as atypical pneumonia, from March 2009 to March 2010. The diagnosis was established H1N1 influenza / 09 pandemic with RT-PCR positive. It describes the type of condition (unilateral or bilateral), distribution (focal, multifocal or diffuse), the predominant site (basal, medial, apical) and the CT pattern (interstitial, consolidated or ground-glass opacity) and pleural fluid identification (Figure 3)

10. EVALUATION. Figure 4. Ageporcentage Figure 5. Agerange The records were obtained from 13 patients: 11 male/2 female (Figure 4) with maximum age 65, minimum 12, average of 36 years (Figure 5), with RT-PCR positive. All of them have radiography at admission and only 5 were carried out to chest CT.

11. EVALUATION. 3 Days after Image 1a Image 1b 4 Daysafter Image 2b Image 2a We found 4 patients with no radiographic evidence of lung disease. Lung disease was observed in 9/12 (7 bilateral and 2 unilateral), predominantly basal in 8 and 1 medial; 5 with multifocal distribution, 3 with diffuse affection and 1 with focal pattern. None with pleural fluid. The CT pattern observed was consolidation affection and ground glass attenuation pattern 4 patients had radiographic and 1 patient CT follow-up during hospital stay (Images 1a,b & 2a,b).

12. DISCUSSION Table.1 Total of confirmed cases bymonth of March,2009 to March,2010 in Mexico. The first cases of influenza in Mexico were detected in April, 2009 appearing 4,167 suspicious cases and 313 confirmed cases. On March 24, 2010 the Office of Health of the Government has reported of 72.265 confirmed cases and 11.136 deaths (Table 1), http://portal.salud.gob.mx/contenidos/noticias/influenza/estadisticas.html

13. DISCUSSION Few studies describe the radiological pattern seen in patients with pandemic influenza H1N1/09. Influenzae H1N1 epidemic in our country was a challenge in the detection and treatment. It`s important to consider to characterize the disease by imaging methods. There are few publications that could characterize the radiographic and CT findings. In our 12 patients we diagnosed with H1N1 Influenzaeadmitted to our hospital using both radiographic and CT findings and laboratories results, as we show. Perez, Zamboni et al. (2009) published a series of 18 cases, of H1N1 in Mexico. Investigators reported that patchy bilateral opacities were seen on radiography in all patients and that one CT image showed ground-glass air-space density. Although that report provided a limited description of the radiologic features. N Engl J Med. 2009 13;361(7):680-9.

14. DISCUSSION Abella H.A. (2009) describes a rapidly progressive (24 to 72hrs) condition characterized by basal interstitial pattern of consolidation and ground-glass opacities, similar findings to SARS radiological patterns, but did not report a total number of cases analyzed. It was only a summary of the findings cited by private and public hospitals. Diagnostic Imaging. 2009 30;1-2 Mollura D.J. (2009) describesperipheralradiopacitiespulmonary by x-ray, & CT scanshowed in one patient a condition in peribronchialground-glass opacities . AJR2009,193:1494-1499 and 1500-1503

15. DISCUSSION The study most similar to our experience and with which we can make the comparison of our findings was performed by Ajlanet al (2009). They published the radiographic and CT findings of 7 patients diagnosed with H1N1. Investigators reported 4/7 patients witch initial chest radiography was normal. In 2/4 patients, the follow-up radiograph 2 days later showed the development of bilateral symmetric lower lobar ground-glass opacities and consolidations. The most common MDCT findings in 3 patients with infection was ground-glass opacities and areas of consolidation with a predominant peribronchovascular and subpleural distribution, resembling organizing pneumonia. AJR2009; 193:1494-1499

16. DISCUSSION Our population: 4/13 young patients with (+) positive lab test, had no radiographic evidence of disease. They were treated quickly with antiviral and follow-up without radiographics changes. 3/13 patients had pulmonary x-rayfindings: Consolidation and interstitial (septal linear opacity nodular) with rapid progression of the disease (24-48 hours). The most common MDCT results in 6/13 patients showed interstitial affection and consolidation (ground-glass opacity or nodular), bilateral, predominantly basal with multifocal and diffuse distribution. There wasn´t pleural effusion. Similarsdata was obtained by the Ajlan et al.The number of patients is higher in our study as well as the tracking number and MDTC studies.

17. DISCUSSION The most common MDCT showed interstitial affection and consolidation (ground-glass opacity or nodular), bilateral, predominantly basal with multifocal and diffuse distribution which persisted in the follow with MDCT in just one case. (Images 3a to f) a b c d e f

18. A B C EXAMPLES OF RADIOGRAPHIC PATTERNS OF PULMONARY AFFECTION: Images: (A and B) patients with normal radiography, (C) patient with basal interstitial affection, (D and E) patient with consolidation and Interstitial (linear septal and opacity nodular ) multifocal y (F) patient with interstitial pattern (linear septal and opacity nodular ) diffuse and bilateral. D E F

19. A B EXAMPLES OF CT PATTERNS OF PULMONARY AFFECTION: Images: (A and B) patients with interstitial and consolidation affection (linear septal and ground- glass opacity) diffuse and bilateral, (C) patient with consolidation (ground-glass opacity or nodular), bilateral and multifocal y (D) patient with interstitial affection Interstitial (linear septal and ground- glass opacity) bilateral. C D

20. PandemicMexican H1N1/09 Influenzae: Radiological & CT findings. Cases presentation

21. Cases 1-4. of patients with Influenzae H1N1/09 with normal Chest radiography obtained at hospital admission. 1 2 3 4

22. B A Case 5. 43-year-old man with Influenzae H1N1/09 (A ) Chest X-ray obtained at hospital admission shows subtle diffuse unilateral Increase in density (blue circle). (B) Chest X-rad obtained 4 day after. (C) MDCT obtained 10 day after shows affection linear septal and ground- glass opacity (red arrow). C

23. A B C Case 6. 48-year-old woman with Influenzae H1N1/09. (A and D) Chest X-ray and MDCT obtained at hospital admission shows extensive ground-glass opacities multifocal (red arrow ) and bilateral consolidation. (B) Chest X-ray obtained 4 day after shows extensive ground-glass diffusean bilateral. D

24. Case 7. 54-year-old man with Influenzae H1N1/09 (A and B ) Chest X-ray and MDCT obtained at hospital admission shows consolidation (ground-glass opacity), bilateral and multifocal. (red arrow) A B

25. A Case 8. 65-year-old man with Influenzae H1N1/09. (A) Chest MDCT obtained at hospital admission shows interstitial affection and consolidation (linear septal and ground- glass opacity) bilateral. (B) Chest MDCT obtained 1 year after shows interstitial (ground-glass), bilateral. B

26. Case 9. 60-year-old women with Influenzae H1N1/09. (A) Chest X-ray obtained at hospital admission shows interstitial affection (blue circle) (B) Chest X-ray obtained 4 days after shows consolidation (linear septal and ground-glass opacity) bilateral y (C) Chest MDCT obtained 5 days after shows interstitial and consolidation bilateral (ground-glass) (red arrow). A B C

27. CONCLUSION. PandemicMexican H1N1/09 Influenzae: Radiological & CT findings.

28. CONCLUSION. Chest radiographs were normal in young patients. Others patients had radiographic abnormalities such as: Consolidation and interstitial, linear septal and opacity nodular. MDCT can help clinicians monitor changes causedfor H1N1 infection. We observed that the predominant pattern was Interstitial and Consolidation (ground-glass opacity or nodular).

29. References Trifonov V, Khiabanian H, Rabadan R ; Geographic dependence, surveillance, and origins of the 2009 influenza A (H1N1) virus, N Engl J Med. 2009 Jul 9;361(2):115-9. Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza; Clinical Aspects of Pandemic 2009 Influenza A (H1N1) Virus Infection N Engl J Med 2010; May 362:1708-1719. Blyth CC, Iredell JR, Dwyer DE; Rapid-test sensitivity for novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009 Aug 13;361(7):728-9. http://healthmap.org/en/es.php. Jefferson T, Del Mar C, Liz Dooley L et al; Physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review BMJ 2009; 339:367. SistemaNacional de Información en Salud [National System of Health Care Information]. Mexico City: General Directorate of Health Care Information. (Accessed July 20, 2009, at http://sinais.salud.gob.mx/http://healthmap.org/en/es.php Sistema Nacional de Vigilancia Epidemiológica (SINAVE). Mexico City: MexicoMinistry of Health. (Available at http://www.dgepi.salud.gob.mx/sinave/index.htm http://portal.salud.gob.mx. http://portal.salud.gob.mx/contenidos/noticias/influenza/estadistic. PerezPR, Zamboni DR, De Leon PS, et al; INER WorkingGroupon Influenza. Pneumonia and respiratoryfailurefromswine-origin influenza A (H1N1) in Mexico. N Engl J Med 2009; 361:680 –689. Abella HA; X-rays and CT offerpredictivepowerforswineflu diagnosis; DiagnosticImaging. Vol. No. June 30, 2009 Mollura JD, Deborah S. Asnis, et al; ImagingFindings in a Fatal Case of PandemicSwine-Origin Influenza A (H1N1) Am. J. Roentgenol.,2009; 193: 1500 – 1503 Ajlan MA, Quiney B, Nicolaou S, et al; Swine-Origin Influenza A (H1N1) Viral Infection: Radiographic and CT Findings Am. J. Roentgenol. 2009; 193: 1494 - 1499. . l

30. PandemicMexican H1N1/09 Influenzae: Radiological & CT findings. Gaspar-Alberto Motta-Ramírez, MD gamottar@ yahoo.com.mx Erika Alonso-Blancas, MD eri_alo_bla@hotmail.com Carlos Rodríguez-Treviño & José-Luis Ramírez-Arias, MD Departamento de Radiología e Imagen Hospital Ángeles del Pedregal. México City, MEXICO.

31. PandemicMexican H1N1/09 Influenzae: Radiological & CT findings. This presentation participated in the last RSNA meeting