|Year : 2013 | Volume
| Issue : 2 | Page : 182-187
Characteristics of hospitalized patients with severe and non-severe pandemic influenza a (H1N1) in Saurashtra Region, India (two waves analysis)
Rajesh K Chudasama1, Umed V Patel2, Pramod B Verma2
1 Department of Community Medicine, Meghji Pethraj Shah Medical College, Jamnagar, Gujarat, India
2 Department of Community Medicine, Government Medical College, Rajkot, Gujarat, India
|Date of Web Publication||31-Aug-2013|
Rajesh K Chudasama
Department of Community Medicine, Vandana Embroidary, Mato Shree Complex, Sardar Nagar Main Road, Rajkot 360 001
Source of Support: None, Conflict of Interest: None
Background: In India, the first case of 2009 pandemic influenza A (H1N1) virus infection was reported in May 2009 and the same in Saurashtra region in August 2009. We describe the epidemiology and factors associated with severe and non-severe cases of 2009 influenza A (H1N1) infection reported in the Saurashtra region. Materials and Methods: From September 2009 to January 2011, we reported 511 patients who were infected with 2009 influenza A (H1N1) virus and admitted in different hospitals of Rajkot city. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing was used to confirm infection. Factors associated with severe cases were determined by comparing with non-severe cases. Results: Out of 511 patients, 140 had severe disease (requiring intensive care or died) and 371 non-severe diseases (admitted in wards and survived). Median age of 30 years; median time of 5 days from onset of illness to diagnosis, and 4 days median time was reported for hospital stay among severe disease patients. More than half (60.7%) were females. Out of the patients with severe disease, 52.1% patients residing in urban area (OR = 1.68, CI = 1.13-2.49). Significant association was reported among severe disease patients for delayed referral from general practitioner/physician after initial treatment. All patients received antiviral drug, however, only 27.1% received within 2 days of illness. Presence of coexisting condition (pregnancy (OR = 0.19, CI = 0.08-0.48) was strongly associated with severe disease. Conclusion: Delayed referral from general practitioner/physician, duration of antiviral treatment, presence of coexisting condition (i.e., pregnancy) were responsible for intensive care or mortality among severe influenza A (H1N1) illness.
Keywords: Epidemiology, influenza A (H1N1), intensive care, pregnancy, reverse transcriptase-polymerase chain reaction, severe disease
|How to cite this article:|
Chudasama RK, Patel UV, Verma PB. Characteristics of hospitalized patients with severe and non-severe pandemic influenza a (H1N1) in Saurashtra Region, India (two waves analysis). J Family Med Prim Care 2013;2:182-7
|How to cite this URL:|
Chudasama RK, Patel UV, Verma PB. Characteristics of hospitalized patients with severe and non-severe pandemic influenza a (H1N1) in Saurashtra Region, India (two waves analysis). J Family Med Prim Care [serial online] 2013 [cited 2019 Oct 18];2:182-7. Available from: http://www.jfmpc.com/text.asp?2013/2/2/182/117397
| Introduction|| |
The novel influenza A (H1N1) virus was first detected in Mexico  during April 2009, and then in United States (US).  The scientists call this a 'quadruple reassortant' virus and hence this new (novel) virus is christened "Influenza A (H1N1) virus". , The World Health Organization (WHO) raised the pandemic level from 5 to 6, the highest level, after the documentation of human to human transmission of the virus in at least three countries in two of the six world regions defined by the WHO. 
India reported first confirmed case of influenza A (H1N1) during May, 2009.  Gujarat state reported first H1N1 positive confirmed case during June 2009.  Saurashtra region is the western part of Gujarat state, reported first case in August 2009.  Although many individuals presented with mild, self-limited illness, no signs of pulmonary involvement; some people required intensive care and received maximal life support measures. , The objective of present study was to identify characteristics associated with severity of disease in 511 confirmed cases of pandemic H1N1 influenza, hospitalized in various hospitals of Rajkot.
| Materials and Methods|| |
Total 511 patients found positive for pandemic Influenza A (H1N1) and admitted in different hospitals of Rajkot from September 1, 2009 to January 31, 2011 combining two waves, were included for analysis. Though no cases were reported after November 2010, the surveillance was continued till February 2011.
Categorization of influenza A (H1N1) case
Ministry of Health and Family Welfare (MOHFW), Government of India (GOI) had issued guidelines for categorization of influenza A (H1N1) cases during screening for home isolation, testing treatment, and hospitalization [Table 1].  Current report describes total 511 patients belonging to category C who were tested and confirmed, hospitalized, monitored, and included in the analysis. A confirmed or suspected case was defined as per the MOHFW guidelines. 
|Table 1: Categorization of influenza A (H1N1) patients as per clinical features |
Click here to view
Criteria for intensive care unit admission
All patients were categorized as: (1) Cases as severe influenza A (H1N1) patients - those patients needed intensive care unit (ICU) or died. Patients with one or more of following feature were admitted in ICU: (a) SpO 2 < 60 mm Hg, (b) Not maintaining SpO 2 with oxygen mask, (c) tachypnea and dyspnea, (d) respiratory rate > 40/min, (e) with altered sensorium, (f) patchy consolidation on X ray chest.
(2) Controls as non-severe influenza A (H1N1) patients - those admitted in wards survived and not needed intensive care. Patients not fulfilling any of above criteria were admitted in wards for clinical management.
For patients below 15 years of age following criteria were used to categorize as severe influenza A (H1N1) patients - PaO 2 < 60 mm of Hg, hypercapnoea (pCO 2 > 55 mm of Hg, severe metabolic acidosis (pH < 7.2), severe respiratory distress (respiratory rate > 70/min), severe lower chest wall indrawing, altered sensorium, grasping or apnea, and shock.
Several types of data was collected from the patients: Date and time of admission to hospital/ICU, age, sex, residential status, co-existing conditions, date, and time of first symptoms. Also, as mentioned, data for other variables were collected [Table 2].
|Table 2: Baseline characteristics of 2009 influenza A (H1N1) infected patients in Saurashtra region from September 2009 to January 2011 |
Click here to view
All patients' admission history and their medical records were assessed from swine flu ward for initial clinico-epidemiological details, and from medical record and statistics department after patient discharge/death from various hospitals of Rajkot city. Line list number was given to every patient to avoid duplication at any time during study period. Approval by institutional review board was not required because the present infectious disease was covered under epidemic act and the State Health Department  has implemented the Epidemic Disease Control Act, 1897.
Laboratory confirmation of infection
The influenza A (H1N1) virus was detected with the use of real time reverse transcriptase polymerase chain reaction (RT-PCR) assay by collecting two swabs from naso-pharynx and one from pharynx, in accordance with the protocol from the US centers for Disease Control and Prevention, as recommended by the WHO. 
All data was entered in MS Excel, and analyzed by using Epi Info software (version 3.5.1) from CDC.  Bivariate analysis was done using χ2 test or Fisher`s exact test for analysis. Variables that showed P < 0.20 in bivariate analysis were selected for logistic regression to examine the relation between variables of interest and severity of disease. Results from logistic regression analyses expressed as odds ratio (OR), and 95% confidence intervals (CIs). The P values and CIs reported here reflect a two tailed α level of 0.05.
| Results|| |
Demographic and clinical characteristics of patients
Out of 511 cases of influenza A (H1N1), 140 patients (27.4%) reported with severe disease and 371 patients (72.6%) as non-severe disease [Table 2]. Among 140 severe disease patients, mortality was reported in majority (90.7%) patients, while only 9.3% patients needed intensive care and survived. Month-wise distribution of influenza A (H1N1) infected patients for two waves is shown in [Figure 1].
|Figure 1: Month wise distribution of infected influenza A (H1N1) cases from September 2009 to January 2011 in Saurashtra region|
Click here to view
The median age of 30 years was reported in both severe (range 4 months to 68 years) and non-severe disease patients (range 1 month to 70 years). More females (60.7%; OR = 0.53, CI = 0.36-0.79) needed intensive care than males. Total 47 (31.3%) cases had an underlying medical condition [Table 3], reported more among severe disease patients (33.6%). Diabetes mellitus (DM) (10.2%) and/or hypertension (11.9%) was mainly reported underlying condition among non-severe disease. However, pregnancy (10.0%; P < 0.05) was reported mainly among patients with severe disease [Table 3]. Among reported female patients, 14 were pregnant with a range of 4 to 9 months of amenorrhea, A significant risk of severe disease was reported with pregnancy (OR = 0.19, CI = 0.08-0.48) . Various laboratory and radiological findings were reported [Table 4].Pneumonia was reported more among patients with severe disease (86.7%; OR = 0.30, CI = 0.16-0.53) [Table 5].
|Table 3: Clinical features and coexisting conditions among influenza A (H1N1) infected patients |
Click here to view
|Table 4: Laboratory and radiological findings of influenza A (H1N1) infected patientsa |
Click here to view
|Table 5: Correlates of disease severity among severe (N=140) and non-severe (N=371) influenza A (H1N1) patients|
Click here to view
More than half of the patients with severe disease, that is, 58.6% and 44.5% non-severe disease patients were first treated by general practitioner/physician and then referred to a higher centre (OR = 0.56, CI = 0.38-0.83). Among 140 severe disease patients who needed intensive care, 90.7% reported mortality and 9.3% survived.
All patients received the antiviral drug, oseltamivir [Table 2]. Out of 140 severe disease patients, 27.1% received antiviral drug within 2 days of onset of illness. Median time of 3 days for ventilator support, more than 5 days hospitalization (P < 0.05), and antiviral drug administration (P < 0.05) has been reported among severe disease patients.
| Discussion|| |
Present study mentions severe influenza A (H1N1) virus infection in residents of Saurashtra region. A total of 511 patients reported confirmed and were hospitalized during the study period, and categorized as patients having severe (N = 140) and non-severe disease (N = 371).
Patients with severe diseases reported median age of 30 years which is higher than that of Portugal (23)  and South Korea (11),  but lower than that was observed in a study from Canada (37).  Two-third patients with severe disease were above the age group of 25 years in which 60.7% were females. It indicates that adults and females  (OR = 0.53, CI = 0.36-0.79) appear to be at higher risk of death due to pandemic influenza A (H1N1) virus infection compared to children or teenagers. More cases of severe influenza were reported from the urban area (OR = 1.68, CI = 1.13-2.49) than rural area.  This may be because of dense population in urban area favors spread of virus infection.
Among all the patients, a median time of 5 days was reported from onset of illness to diagnosis of influenza A (H1N1). More than half (58.6%) of the patients with severe disease were treated first at general practitioner/physician (OR = 0.56, CI = 0.38-0.83) and then referred to a higher center. The time duration between onset of illness and hospital admission and diagnosis was more than other countries. , The possible justification is that patients seek treatment at local level from general practitioners and physicians, but with no or little improvement after initial treatment, they were referred to a higher center for further investigation and management. Present study reported median time of 4 days for hospital stay among severe disease patients (OR = 0.24, CI = 0.16-0.37) with 65.7% patients having less than 5 days of hospital stay; compared to 7 days median time and 32.4% non-severe disease patients. It also indirectly reflects that patients with more severe disease with delayed referral, reaches to higher center at critical stage.
Current interim CDC guidelines for pandemic and seasonal influenza recommended the use of either oseltamivir or zanamivir for hospitalized patients.  Indian government authorities have recommended and supplied oseltamivir to the state governments for distribution in tertiary care centers and district. In the present study area, all the influenza A (H1N1) infected fatal cases received oseltamivir after hospital admission. However, only 27.1% severe disease patients received it within 2 days of onset of illness which when compared was higher in China (12.8%),  but lower than in United States (38-50%).  Initial primary treatment at general practitioners or local physician level and delayed referral to higher center and investigation, may be a possible explanation for delayed start of oseltamivir in suspected or confirmed influenza A (H1N1) patients. When started early, antiviral drug has beneficial effect. Study reported that patients admitted to ICU or died were less likely to receive such therapy within 48 hours after onset of symptoms.  After complete course of oseltamivir therapy (OR = 0.38, CI = 0.22-0.67), the present study shows 90.7% mortality in severe disease patients which when compared is higher than that reported in Turkey (50.8%).  This is possibly because of delayed referral and initiation of antiviral drug.
Month wise distribution shows two different waves. During the first wave, number of cases increases rapidly from December 2009 onwards. Highest positive cases (124) were reported during January, followed by decline upto March 2010. It signifies the relationship between influenza virus and cold season, as maximum number of cases occurs during these months of winter season. , Second wave starts from August, 2010 to November 2010. No cases were reported thereafter. The second wave had started in monsoon season, suggesting that high humidity may favor the spread of influenza A (H1N1).
Present study reported that majority of the patients in both categories had cough, fever, shortness of breathing, and sore throat, likewise patients of US  and Canada.  Current study reported that 42.5% severe influenza A (H1N1) patients have any one coexisting condition (OR = 0.53. CI = 0.31-0.90), which was 53% in France,  and 57.7% in China.  Pregnancy was a well documented risk factor for severe infection and death in seasonal influenza and in previous pandemics. , In this study, pregnancy was reported as a risk factor (OR = 0.22, CI = 0.06-0.76) in 11.5% severe influenza A (H1N1) cases than among non-severe influenza A (H1N1) cases. ,, Out of ten severe disease pregnant cases, two were in second trimester and eight were in third trimester.
Pneumonia was reported more among patients with severe disease (86.7%; OR = 0.30, CI = 0.16-0.53), higher than that reported in Korea (70.7%)  and Brazil.  In absence of accurate diagnostic methods, patients who were hospitalized with suspected influenza and lung infiltrates on chest radiography should be considered for treatment with both antibiotics and antiviral drugs. 
Our study also has some limitations. The data was taken only from hospitalized patients. Therefore, patients who were infected in the community and did not go to the hospital were not included in our study. All diagnostic testing was clinically driven, and other investigations were not obtained in a standardized fashion. Despite the use of a standardized data collection form, not all information was collected for all patients.
Considering association between coexisting condition and severity of disease, it is possible that the presence of a coexisting condition that makes ICU admission more likely might also have made ascertainment of virologic infection, thus producing an inflated estimate of any potential association. With regards to the present study, the relative impact of the direction of this type of selection bias, known as Berksonian bias, is uncertain.
| Conclusion|| |
The severity of illness among influenza A (H1N1) infected patients was associated with delayed referral from general practitioner/physician, duration of antiviral treatment, and presence of coexisting condition, especially pregnancy. These findings may be different during the future waves, owing to the timely deployment of an effective vaccine, to viral mutation, and resistance to antiviral drugs.
| Acknowledgment|| |
Authors are thankful to Chief Medical Officer, Civil Hospital, Rajkot and other private hospitals for providing the necessary data. Authors are also thankful to the staff members of community medicine department, nursing staff of swine flu ward, and medical record department of Medical College and Civil Hospital, Rajkot for helping in providing necessary records and information.
| References|| |
|1.||Neumann G, Noda T, Kawaoka Y. Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 2009;459:931-9. |
|2.||Swine influenza A (H1N1) infection in two children: Southern California, March-April 2009. Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep 2009;58:400-2. |
|3.||Ministry of Health and Family Welfare, Government of India: Factsheet Influenza A (H1N1) 2010. Available from: http://pib.nic.in/h1n1/h1n1.asp. [Last accessed on 2012 May 21]. |
|4.||Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, et al. Antigenic and genetic characteristics of swine origin 2009 A (H1N1) influenza viruses circulating in humans. Science 2009;325:197-201. |
|5.||World Health Organization. Influenza A (H1N1) - update 14. Geneva (2009). Available from: http://www.who.int/csr/don/2009_05_04a/en/index.html. [Last accessed on 2012 May 21]. |
|6.||Transmission dynamics and impact of pandemic influenza A (H1N1) 2009 virus. Wkly Epidemiol Rec 2009;84:481-4. |
|7.||The Times of India. First swine flu case surfaces in Gujarat. 18 th June, 2009. Available from: http://timesofindia.indiatimes.com/city/ahmedabad/First-swine-flu-case-surfaces-in-Gujarat/articleshow/4669250.cms. [Last accessed on 2012 May 21]. |
|8.||The Indian Express. Saurashtra's first confirmed swine flu case detected. 19 th August, 2010. Available from: http://www.expressindia.com/latest-news/saurashtras- first-confirmed- swine-flu-case- detected-in- bhavnagar/503678/. [Last accessed on 2012 May 22]. |
|9.||Gutiérrez-Cuadra M, González-Fernández JL, Rodríguez-Cundin P, Fariñas-Álvarez C, San Juan MV, Parra JA, et al. Clinical characteristics and outcome of patients with pandemic 2009 Influenza A (H1N1) v virus infection admitted to hospitals with different levels of health-care. Rev Esp Quimioter 2012;25:56-64. |
|10.||Kumar A, Zarychanski R, Pinto R, Cook DJ, Marshall J, Lacroix J, et al. Critically ill patients with 2009 influenza A (H1N1) infection in Canada. JAMA 2009;302:1872-9. |
|11.||Ministry of Health and Family Welfare, Government of India: Guidelines on categorization of influenza A H1N1. May, 2009. Available from: http://www.mohfw-h1n1.nic.in/Guidelines.html. [Last accessed on 2010 Jan 15]. |
|12.||Human swine influenza: A pandemic threat. Director General of Health Services. Government of India. CD Alert 2009;12:1-8. |
|13.||Ministry of Health and Family Welfare, Government of Gujarat: Epidemic Disease Control Act, 1897. Available from: http://www.expressindia.com/latest-news/epidemic-control-act- invoked-to-thwart-h1n1-scare-in-state/504144/. [Last accessed on 2012 May 22]. |
|14.||World Health Organization: CDC protocol of realtime RT-PCR for swine influenza A (H1N1). Geneva. April 28, 2009. Available from: http://www.who.int/csr/resources/publications/swineflu/CDCrealtimeRTPCRprotocol_20090428.pdf. [Last accessed on 2012 May 21]. |
|15.||Centers for Disease Control and Prevention: Epi Info version 3.5.1, 2008. Available from: www.cdc.gov/epiinfo/. [Last accessed on 2012 May 21]. |
|16.||Duque V, Vaz J, Mota V, Morais C, Da Cunha S, Meliço-Silvestre A. Clinical manifestations of pandemic (H1N1) 2009 in the ambulatory setting. J Infect Dev Ctries 2011;14:658-63. |
|17.||Rhim JW, Go EJ, Lee KY, Youn YS, Kim MS, Park SH, et al. Pandemic 2009 H1N1 virus infection in children and adults: A cohort study at a single hospital throughout the epidemic. Int Arch Med 2012;5:13. Available from: http://www.intarchmed.com/content/5/1/13. [Last accessed on 2012 May 23]. |
|18.||Helferty M, Vachon J, Tarasuk J, Rodin R, Spika J, Pelletier L. Incidence of hospital admissions and severe outcomes during the first and second waves of pandemic (H1N1) 2009. CMAJ 2010;182:1981-7. |
|19.||Zarychanski R, Stuart TL, Kumar A, Doucette S, Elliott L, Kettner J, et al. Correlates of severe disease in patients with 2009 pandemic influenza (H1N1) virus infection. CMAJ 2010;182:257-64. |
|20.||Jain S, Schmitz AM, Louie J, Druckenmiller JK, Chugh R, Deutscher M, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 2009;361:1935-44. |
|21.||Centers for Disease Control and Prevention: Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009-2010 seasons. Atlanta. Available from: http://www.cdc.gov/h1n1flu/recommendations.htm. [Last accessed on 2012 May 21]. |
|22.||Xi X, Xu Y, Jiang L, Li A, Duan J, Du B, et al. Hospitalized adult patients with 2009 influenza A (H1N1) in Beijing, China: Risk factors for hospital mortality. BMC Infect Dis 2010;10:256. |
|23.||Truelove SA, Chitnis AS, Heffernan RT, Karon AE, Haupt TE, Davis JP. Comparison of patients hospitalized with pandemic 2009 influenza A (H1N1) virus infection during the first two pandemic waves in Wisconsin. J Infect Dis 2011;203:828-37. |
|24.||Teke T, Coskun R, Sungur M, Guven M, Becki TT, Maden E, et al. 2009 H1N1 influenza and experience in three critical care units. Int J Med Sci 2011;8:270-7. |
|25.||Vaillant L, La Ruche G, Tarantola A, Barboza P, epidemic intelligence team at InVS. Epidemiology of fatal cases associated with pandemic H1N1 influenza 2009. Euro Surveill 2009;14:19309. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19309. [Last accessed on 2012 May 22]. |
|26.||Deng LH, Zeng YL, Feng P, Liu YL, Wang LC, Bai Y, et al. Clinical characteristics of critical patients with pandemic influenza A (H1N1) virus infection in Chengdu, China. J Zhejiang Univ Sci B 2012;13:49-55. |
|27.||Jamieson DJ, Honein MA, Rasmussen SA, Williams JL, Swerdlow DL, Biggerstaff MS, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009;374:451-8. |
|28.||Wilking H, Buda S, von der Lippe E, Altmann D, Krause G, Eckmanns T, et al. Mortality of 2009 pandemic influenza A (H1N1) in Germany. Euro Surveill 2010;15:19741. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19741. [Last accessed on 2012 May 21]. |
|29.||Oh WS, Lee SJ, Lee CS, Hur JA, Hur AC, Park YS, et al. A prediction rule to identify severe cases among adult patients hospitalized with pandemic influenza A (H1N1) 2009. J Korean Med Sci 2011;26:499-506. |
|30.||Lenzi L, Mello ÂM, Silva LR, Grochocki MH, Pontarolo R. Pandemic influenza A (H1N1) 2009: Risk factors for hospitalization. J Bras Pneumol 2012;38:57-65. |
|31.||Harper SA, Bradley JS, Englund JA, File TM, Gravenstein S, Hayden FG, et al. Seasonal influenza in adults and children-diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: Clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009;48:1003-32. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
|This article has been cited by|
||Safety and effectiveness of neuraminidase inhibitors in situations of pandemic and/or novel/variant influenza: a systematic review of the literature, 2009–15
| ||C. Boikos,C. Caya,M. K. Doll,H. Kraicer-Melamed,M. Dolph,G. Delisle,N. Winters,G. Gore,C. Quach |
| ||Journal of Antimicrobial Chemotherapy. 2017; |
|[Pubmed] | [DOI]|
||A study of an influenza A (H1N1)pdm09 outbreak in pregnant women in Rajasthan, India
| ||Abhishek Agrawal,Sujata Agarwal,Vinay Kumar,Chuttan L. Nawal,Pradeep Mital,Radheyshyam Chejara |
| ||International Journal of Gynecology & Obstetrics. 2016; 132(2): 146 |
|[Pubmed] | [DOI]|
||Sex-based differences in immune function and responses to vaccination
| ||S. L. Klein,I. Marriott,E. N. Fish |
| ||Transactions of the Royal Society of Tropical Medicine and Hygiene. 2015; 109(1): 9 |
|[Pubmed] | [DOI]|