key: cord-0006509-e2xgrya6 authors: Örnek, Tacettin; Yalçın, Funda Demirtaş; Ekin, Selami; Yalçın, Şaban; Yemişen, Mücahit title: Pneumonia in patients with novel influenza A (H1N1) virus in Southeastern Turkey date: 2011-02-01 journal: Wien Klin Wochenschr DOI: 10.1007/s00508-011-1537-z sha: 65e058593f16a20803e316d83520aed17b8319b9 doc_id: 6509 cord_uid: e2xgrya6 The objective of this study was to describe the clinical characteristics and the radiological and laboratory findings of the hospitalised patients who had novel, laboratory-confirmed, swine-origin influenza A virus (S-OIV) infection with pneumonia. Between October and December 2009, 56 patients hospitalised for pneumonia who were tested for S-OIV infection were retrospectively evaluated. Thirty-three patients had positive S-OIV infections. In addition, 23 of the 56 patients who had negative test results for S-OIV infection were compared with the positive group. The mortality rate amongst the patients with S-OIV infection was 24.2%. Of the 33 patients, 42.4% had at least one underlying medical condition and 4 (12%) patients were pregnant or postpartum. Fourteen patients (42.4%) with S-OIV infection were followed up in an intensive care unit. The most common symptom was dyspnea. The mean peak body temperature during hospital stay (39.42 ± 0.70) was higher in this group than in the negative group (38.51 ± 1.05) (p = 0.001). Thrombocytopenia, increased creatine kinase and elevated lactate dehydrogenase levels were statistically significant. Bilateral infiltration was more common in the patients with S-OIV infection. Although some laboratory, radiological and clinical data show a significant difference between the patients with S-OIV pneumonia and the negative group, each patient presenting with signs of pneumonia during pandemia should be tested for Influenza A. Swine infl uenza (H1N1) is a novel infl uenza A virus comprising a reassortment of four distinct genetic elements, swine, human, avian, and Eurasian swine genetic components, which combine to form a single infl uenza virus [1] . Th e fi rst human infections with the new swine-origin infl uenza A virus (S-OIV) were confi rmed in April 2009 in Mexico and the United States. Since then, Turkey and several other countries experienced outbreaks of respiratory illness caused by S-OIV. On 11 June 2009, WHO announced a global 2009 infl uenza pandemic [2] . On 16 May 2009, the fi rst infection by S-OIV in Turkey was reported. Outbreak spread throughout the country during the winter wave; the fi rst death due to S-OIV infection in Turkey occurred on 24 October 2009. Previous studies have reported that a prominent clinical feature of S-OIV infection is severe pneumonia [3] [4] [5] . In this report, we aim to describe the clinical characteristics and the radiological and laboratory fi ndings of patients with H1N1 virus pneumonia who lived in the southeastern region of Turkey. Attempts to defi ne specifi c clinical or laboratory parameters to distinguish S-OIV from other types of pneumonia might facilitate early suspicion of S-OIV infection. Th is study was performed at Şanlıurfa Education and Research Hospital, which is located in the southeastern region of Turkey. We retrospectively reviewed medical charts and radiological and laboratory fi ndings of the patients who were followed up at the hospital between 27 October 2009 and 26 December 2009. We enrolled all hospitalised patients with pneumonia for whom nasopharyngeal swab specimens were collected due to suspected S-OIV infection. We separated the patients into two groups. In the positive group, 33 patients had laboratory-confi rmed S-OIV infection. Twenty-three patients without an S-OIV infection (confi rmed by laboratory tests) were used to document the diff erences between the patients with or without S-OIV infection. Nasopharyngeal swab specimens were collected upon admission and kept at a temperature ranging from 4 to 8°C. Specimens were sent to a Turkish government health ministry laboratory centre called "Refi k Saydam Hıfsızsıhha Center Presidency" (RSHCP). Specimens were tested using real-time reverse-transcriptasepolymerase-chain-reaction (rRT-PCR), in accordance with the guidelines provided by the WHO. At the national infl uenza centre of RSHCP, diagnosis of infl uenza and viruses-forming infl uenzalike illness was achieved using primers and probe sequence provided by the U.S. Centers for Disease Control (CDC) [6] . Data analysis was conducted using SPSS 11.5 statistical software. Continuous variables were summarised as means (± SD) or medians (with interquartile ranges). A P value of less than 0.05 was considered statistically signifi cant. Mann-Whitney U-test, Chisquare test, or Fisher's exact test was used as appropriate. All values were two-sided. Demographic characteristics of the patients with S-OIV infection are shown in Table 1 . Th e minimum and maximum ages of the positive group were 13 and 70 years, respectively, with a median age of 30 years. Th e median age of the negative group was 34 years, with a range of 15-80 years; 57.6% of the positive group and 69.6% of the negative group had no comorbidities. In the positive group, 9 of 33 patients had pulmonary disease, such as chronic obstructive pulmonary disease (COPD) or asthma, 3 patients were pregnant, 2 patients had type 2 diabetes mellitus and 1 patient was postpartum. Other comorbidities in the positive group were Down syndrome (n = 1), hypertension (n = 1) and congestive heart failure (n = 1). Th ere were no pregnant or postpartum patients in the negative group, and 4 of 23 patients had pulmonary disease, such as chronic obstructive pulmonary disease (COPD) or asthma. Fourteen patients (42.4%) in the positive group and 8 patients (34.8%) in the negative group were followed up in the intensive care unit (ICU). Th e duration of hospital stay (6.42 ± 4.56 days) and ICU stay (6.0 ± 6.0) in the positive group was lower than in the negative group (8.0 ± 5.50 days, 7.37 ± 7.55 days, respectively), but this difference was not statistically signifi cant (p = 0.296 and 0.810, respectively). A comparison of the symptoms between the groups during admission is shown in Table 2 . Th e most common symptom was dyspnea in the positive group. Dyspnea and sore throat were more common in the positive group (p = 0.015 and 0.039, respectively). In auscultation, crackles were identifi ed in 63.6% (n = 21) of the positive group. 54.5% of the crackles were bilateral. Cyanosis and mental confusion were seen more frequently in the positive group (n = 11, 33.3% and n = 15, 45.5%, respectively) than in the negative group (n = 3, 13.0% and n = 7, 30.4%, respectively) but this diff erence was not statistically signifi cant (p = 0.258 and 0.120, respectively). Th e mean highest body temperature during the hospital stay of the positive group (39.42 ± 0.70) was higher than that of the negative group (38.51 ± 1.05) (p = 0.001). Th e frequency of mechanical ventilation (MV), Acute Respiratory Distress Syndrome (ARDS) and death was higher than in the negative group, but this diff erence was not statistically signifi cant (p = 0.496, 1 and 0.172, respectively) ( Table 3 ). Neither patients in the positive group with ARDS nor those who underwent MV survived. A complete blood cell count was performed on all 33 patients and on the negative group. Th e results of the blood cell count and other biochemical parameters are shown in Table 4 . Th rombocytopenia, increased creatine kinase and elevated lactate dehydrogenase levels were observed in the patients with S-OIV infection (p = 0.007, 0.014 and 0.019, respectively). Th e mean value of platelet count was 202.575 ± 129.600 and 283.608 ± 133.290 in the positive group and negative group, respectively (p = 0.002). Th e mean value of creatine kinase and serum creatinin was higher in the positive group (337.40 ± 385.14 and 0.82 ± 0.31, respectively) than in the negative group (191.89 ± 327.63 and 0.67 ± 0.19, respectively) (p = 0.033 and 0.026, respectively). Th e mean arterial PO 2 of the patients with S-OIV and the S-OIV negative group was 50.5 ± 8.81 (n = 11) and 56.8 ± 11.06 (n = 6), respectively (p = 0.262). Th e mean pH of arterial blood was 7.34 ± 0.06 (n = 11) and 7.34 ± 0.18 (n = 6) in the positive group and negative group, respectively (p = 0.288). In 11 patients with S-OIV infection, bacterial cultures of sputum or bronchial aspirate samples were obtained during the hospital stay. Specimens were negative, with the exception of two samples, which were positive for Pseudomonas aeruginosa. Each of the blood specimen cultures taken from 10 patients was negative. Each of the blood specimen cultures, bronchial aspirate samples or bacterial cultures of sputum taken from 11 of 23 patients belonging to the negative group was also negative. All patients had opacities on a chest radiograph. Bilateral infi ltration was seen more frequently in the patients with S-OIV infection (n = 19, 57.6%) as compared to the negative group (n = 7, 30.4%) (p = 0.044). In 27.3% (n = 9) of the positive group, bilateral expansive infi ltration on upper, medial and lower zones was observed, but there were no patients in whom infi ltration extended throughout the lung zones in the negative group (p = 0.007). Pneumothorax and pleural eff usion were seen in two diff erent patients. All of the patients received oseltamivir upon admission, at a dose of 75 mg twice a day. Oseltamavir treatment was maintained for 5 days in the patients with S-OIV infection, but in the negative group, the duration of oseltamivir treatment was limited by the time required to obtain negative laboratory test results for S-OIV. After admission, 17 patients with S-OIV received ceftriaxone and others received ceftriaxone combined with other antibiotics (13 received clarithromycin, 1 received levofl oxacin, 1 received moxifl oxacin). Other initial treatments were imipenem or meropenem for 7 patients (one combined with vancomycin), moxifl oxacin for 2 patients, piperacillin-tazobactam combined with ciprofl oxacin for 2 patients, sulbactam-ampicillin for 2 patients, cefazolin sodium for 2 patients and sulbactam-cefoperazon for 1 patient. Additional antibiotics were prescribed for several patients, on the basis of their clinical course: four were given imipenem or meropenem (combined with vancomycin in two patients); one, piperacillin-tazobactam + vancomycin and one, sulbactamcefoperazon + vancomycin. We describe the clinical, radiological and laboratory features of pneumonia that developed in the patients with S-OIV infection. Th e most common symptom was dyspnea. Th e mean peak body temperature during hospital stay amongst patients with S-OIV infection was higher than in the negative group (p = 0.001). Th rombocytopenia, increased creatine kinase and elevated lactate dehydrogenase levels were observed in the patients with S-OIV infection. Bilateral infi ltration was seen more frequently in the patients with S-OIV infection (p = 0.044). Swine infl uenza pneumonia was seen in 66% of hospitalised patients with S-OIV infection [7] . Th is number varied in some studies [3, [8] [9] [10] [11] [12] , as did the number of hospitalised patients associated with patient characteristics. All of the patients were living in the Şanlıurfa province of Turkey and were followed at Şanlıurfa Education and Research Hospital, located in the southeastern region of Turkey. Th e mean age of the patients with swine infl uenza pneumonia was lesser than the patients with communityacquired pneumonia. Th e frequency of comorbidity in the patients with swine infl uenza pneumonia was similar to that reported by Perez-Padilla et al. [4] . Most of the studies suggest that some younger and healthy people, especially middle-aged adults and pregnant women, were severely aff ected by S-OIV infection [3] [4] [5] [13] [14] [15] [16] . One study showed that the new H1N1 virus causes pneumonia in ferrets, which is moderate in severity compared to that caused by seasonal H1N1 virus [17] . If we assume that the severity is the same as observed for patients admitted to the ICU in our study, there is no diff erence between healthy and comorbid patients with regard to severity. Extremes in age and multiple and debilitating underlying medical conditions might be contributing to the severity of illness in these patients. Primary viral pneumonia is the most common fi nding in the patients with severe S-OIV infection [11] . Th e onset of swine infl uenza pneumonia is often abrupt. In adults with S-OIV, pneumonia presents as an infl uenza-like illness with a temperature higher than 39°C (102°F) accompanied by prominent myalgia [1] . Th e most consistent symptoms were cough, sore throat, sputum, dyspnea and fever that varied in diff erent studies [4, 13, 18, 19] . In our study, dyspnea and sore throat were most common in swine infl uenza pneumonia. Th e most consistent laboratory characteristics in our patients with S-OIV infection were thrombocytopenia, increased creatine kinase and elevated lactate dehydrogenase levels. Venkata et al. [20] demonstrated that thrombocytopenia was common in ICU patients. In the reports from Chile [21] and Italy [12] , 20% and 27% of the patients with S-OIV had thrombocytopenia, respectively. More commonly reported in children, myositis associated with infl uenza A and B has been well documented and appears to occur most often during the convalescent phase of illness [22] . Th e elevation of lactate dehydrogenase and creatine kinase levels in swine infl uenza pneumonia is consistent with previous reports of pneumonia associated with S-OIV in Mexico, most likely due to myositis [4] . In our study, the mortality rate of swine infl uenza pneumonia (24.2%) was higher than in the negative group (8.7%), but this fi nding was not statistically signifi cant (p = 0.172). We do not currently know whether our patients had coinfection with other respiratory viruses. During the 1918 pandemic, a large number of deaths were associated with bacterial infection [23] , but concurrent bacterial infection does not appear to be a major contributing factor to the severity of illness in our patients, possibly in part because most received antibiotics during hospitalisation. Delayed admission, delayed initiation of oseltamivir therapy and coinfection with other respiratory viruses could be contributing factors for death in our patients. Higher mortality rates and higher frequency of ARDS and MV as well as lower mean PO2 values in the patients with swine infl uenza pneumonia show that there was a tendency towards severe illness, as compared with community-acquired pneumonia. In a study from California, 102 of 227 mechanically ventilated patients with S-OIV infection died [7] . In our study, the small number of mechanically ventilated patients may have skewed the results. In a report from Mexico, most deaths occurred in patients with S-OIV pneumonia who required MV on admission [4] . Another possible cause of high mortality amongst our patients who required MV could be that 8 of 8 patients had transitioned to MV on the fi rst day of admission. Perez-Padilla et al. [4] reported the clinical and ep idemiological features of the fi rst 18 patients with laboratory-confi rmed S-OIV in Mexico. All 18 patients had radio logically confi rmed pneumonia with bilateral patchy alveolar opacities (predominantly basal), aff ecting three or four lung quadrants in 11 patients. Bilateral infi ltrates were seen in 66% (66/100) of the patients in a report from the United States [3] , 94% (64/68) of the patients in a report from China [24] and 59% (10/17) of the patients in a report from Korea [25] . Prachi et al. [26] demonstrated that 71% (20/28) of the patients with S-OIV infection had bilateral Fig. 1 . Axial images from chest computed tomography examination in a patient with swine infl uenza pneumonia. Images show bilateral patchy infiltration on admission day. The patient was discharged from hospital as cured. Bilateral infiltration was seen more frequently in the patients with S-OIV infection (n = 19, 57.6%) than negative group (n = 7, 30.4%) (p = 0.044) involvement on chest radiograph. In this report, 93% of patients that required ICU admission had extensive disease involving ≥ 3 lung zones and all of them had bilateral opacities. Champunot et al. [13] reported that 79.2% (19/24) of the patients had multilobular or bilateral diff use infi ltrate on chest X-ray. Th e report from New Zealand showed that 48% of the patients had multi-lobar infi ltrates [27] . One of the remarkable fi ndings in our study was that 27% of the patients with swine infl uenza pneumonia had infi ltration extending throughout the lung zone, whereas there was not any infi ltration of the entire lung zone in the negative group. Bilateral infi ltration (Fig. 1) was seen more frequently in swine infl uenza pneumonia than in the negative group (p = 0.044). Based on these fi ndings, widespread infi ltrations should alert physicians about distinguishing swine infl uenza pneumonia from community-acquired pneumonia. Our study has several limitations. Firstly, most of the patients were adult (only 3 patients were less than 16 years of age). Secondly, the numbers of patients with and without S-OIV infection were too small to acquire strong statistical data. S-OIV pneumonia is a complication of S-OIV infection and can cause serious illness. 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No fi nancial or other potential confl icts of interest exist. Pneumonia in patients with novel infl uenza A (H1N1) virus wkw 3-4/2011 © Springer-Verlag