|Year : 2014 | Volume
| Issue : 2 | Page : 123-131
A two wave comparison of characteristics of hospitalized patients with severe and non-severe pandemic influenza A (H1N1) 2009 (H1N1pdm09) in Saurashtra Region, India
Rajesh K Chudasama, Umed V Patel, Ravikant R Patel, Ankit Viramgami, Mayur Vala, Sandeep Sharma
Department of Community Medicine, P. D. U. Medical College, Rajkot, Gujarat, India
|Date of Web Publication||11-Aug-2014|
Rajesh K Chudasama
Vandana Embroidary, Mato Shree Complex, Sardar Nagar Main Road, Rajkot - 360 001, Gujarat
Source of Support: None, Conflict of Interest: None
Objective: The primary objective of the following study was to determine and secondarily to compare the clinical and epidemiological characteristics of hospitalized patients with severe and non-severe pandemic influenza A (H1N1) during two waves from September 2009 to January 2011. Materials and Methods: A total of 274 cases were hospitalized during the first wave from September 2009 to March 2010 and from June 2010 to February 2011, 237 cases hospitalized in different hospitals of Rajkot during the second wave. Real-time reverse-transcriptase-polymerase-chain-reaction testing was used to confirm infection. Two wave's comparison was made for factors associated with disease severity. Results: During the first wave 87 (31.8%) patients had severe disease with mortality of 81.6% while during the second wave there were 53 (22.36%) patients having severe disease with higher mortality (94.3%) than the first wave. There were more children up to 15 years of age that required intensive care during the second wave (30.2%) compared to the first wave (20.7%). First wave reported more females and cases from an urban area. Presence of co-existing condition, especially pregnancy was a significant risk factor during the first wave, but not during the second wave. All patients have received antiviral drug oseltamivir during both waves. During the second wave, 39.6% of patients with severe cases received it within 2 days of onset of illness. This was higher than the first wave (19.5%). Conclusion: Higher mortality was reported during the second wave of pandemic influenza A (H1N1) 2009 (H1N1pdm09). There were more cases among the younger age group than adults during the second wave.
Keywords: Disease severity waves, epidemiologic characteristics, influenza A (H1N1)
|How to cite this article:|
Chudasama RK, Patel UV, Patel RR, Viramgami A, Vala M, Sharma S. A two wave comparison of characteristics of hospitalized patients with severe and non-severe pandemic influenza A (H1N1) 2009 (H1N1pdm09) in Saurashtra Region, India. J Mahatma Gandhi Inst Med Sci 2014;19:123-31
|How to cite this URL:|
Chudasama RK, Patel UV, Patel RR, Viramgami A, Vala M, Sharma S. A two wave comparison of characteristics of hospitalized patients with severe and non-severe pandemic influenza A (H1N1) 2009 (H1N1pdm09) in Saurashtra Region, India. J Mahatma Gandhi Inst Med Sci [serial online] 2014 [cited 2019 Oct 21];19:123-31. Available from: http://www.jmgims.co.in/text.asp?2014/19/2/123/138432
| Introduction|| |
The United States (US) Centers for Disease Prevention and Control (CDC) during spring 2009 reported an occurrence of 2009 influenza A (H1N1) in Mexico and California , This virus spreads from human to human and caused world-wide influenza disease. 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.  A variable proportion of patients with pandemic influenza A (H1N1) 2009 (H1N1pdm09) infection were hospitalized. 
During May 2009, India reported first confirmed case of pandemic influenza A (H1N1) 2009 (H1N1pdm09).  Few cases were reported up to August 2009, but thereafter large numbers of positive cases were reported throughout India. First H1N1 positive confirmed case was reported in Gujarat state during June 2009.  Saurashtra region a western part of Gujarat state, reported the first case in August 2009.  Many patients presented with mild, self-limited illness with no signs of pulmonary involvement while some people required intensive care and maximal life support measures. , Initial reports have suggested that, in addition to many of the previously known risk factors, underlying co-morbidities may be the risk factors for severe disease. ,,,,,,,
In severe cases of pandemic influenza A (H1N1) 2009 (H1N1pdm09), the clinical picture is markedly different from the disease pattern seen during epidemics of seasonal influenza, in that many of those affected were previously healthy young people. Current predictions estimate that, during a pandemic wave, 12-30% of the population will develop clinical influenza (compared with 5-15% for seasonal influenza) with 4% of those patients requiring hospital admissions and one in five requiring critical care.  Intensive care units (ICU) play a fundamental role in first pandemic of influenza A (H1N1) virus infection. During the pandemic, a significant number of patients became critically ill primarily because of respiratory failure. Most of these patients required intubation and mechanical ventilation. 
The objective of the present study was to identify and compare clinical and epidemiological characteristics associated with severity of disease in 511 hospitalized cases of confirmed pandemic influenza A (H1N1) 2009 (H1N1pdm09) in Rajkot city, Saurashtra region during two waves from September 2009 to February 2011.
| Materials and Methods|| |
As soon as the first case was reported in May 2009, the Ministry of Health and Family Welfare, Government of India, started preparations for the management of infected patients. Gujarat state (including Saurashtra region) participated in active surveillance for pandemic influenza A (H1N1) 2009 (H1N1pdm09) from August 2009. All those government and private hospitals having advanced ICU were involved in admitting and managing pandemic influenza A (H1N1) 2009 (H1N1pdm09) positive patients in Rajkot. During the first wave from September 2009 to March 2010, total 274 patients found positive and admitted in different hospitals of Rajkot.  Second wave reported from June 2010 to February 2011 with 237 positive patients' hospitalized. Although, there was no confirmed cases reported from December, 2010 onwards, the surveillance was continued up to February 2011.
Categorization of influenza A (H1N1) case
Ministry of Health and Family Welfare, Government of India issued guidelines for categorization of influenza A (H1N1) cases during screening for home isolation, testing treatment and hospitalization as under  :
- Category A: Patients with mild fever plus cough/sore throat with or without body ache, headache, diarrhea and vomiting. These patients don't require oseltamivir and should be treated for the symptoms only; no testing required for H1N1; and monitored for their progress and reassessed at 24-48 h
- Category B
- In addition to all the signs and symptoms mentioned under Category A, these patients have high grade fever and severe sore throat, may require home isolation and oseltamivir; no testing required for H1N1;
- In addition to Category A signs and symptoms, individuals having one or more of the following high risk conditions shall be treated with oseltamivir: Children will mild illness but with predisposing risk factors; pregnant women; persons aged 65 years or older; patient with lung diseases, heart disease, liver disease, kidney disease, blood disorders, diabetes, neurological disorders, cancer and human immunodeficiency virus infection/acquired immunodeficiency syndrome; patients on long-term steroid therapy; no testing required for H1N1;
- Category C: In addition to the above signs and symptoms of Category A and B, these patients have one or more of the following: Breathlessness, chest pain, drowsiness, fall in blood pressure, sputum mixed with blood, bluish discoloration of nails; children with influenza like illness who had a severe disease as manifested by the red flag signs (somnolence, high and persistent fever, inability to feed well, convulsions, shortness of breath, difficulty in breathing, etc.); worsening of underlying chronic conditions; all these patients require testing, immediate hospitalization and treatment. Patients belonged to Category C were enrolled during both waves for the study.
Clinical case/suspected case definition
A suspected case was defined as influenza like illness (temperature >38.0°C and at least one of the following symptoms: Sore throat, cough, rhinorrhea, or nasal congestion) and either a history of travel to a country where infection had been reported or epidemiologic link to a person with confirmed or suspected infection in the previous 7 days. A confirmed case was defined by a positive result of a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay performed at a laboratory operated under the auspices of the state government. 
Criteria for ICU admission
All patients were categorized as:
- Cases as severe pandemic influenza A (H1N1) 2009 (H1N1pdm09) patients - these patients required ICU care or died. Patients with one or more of the following feature were admitted in ICU
- SpO 2 < 60 mm of Hg,
- Not maintaining SpO 2 with an oxygen mask,
- Tachypnea and dyspnea,
- Respiratory rate >40/min,
- Altered sensorium,
- Patchy consolidation on X-ray chest.
- Controls made of non-severe pandemic influenza A (H1N1) 2009 (H1N1pdm09) patients-those admitted into the wards who survived without intensive care. For patients below 15 years of age the following criteria were used to categorize as severe pandemic influenza A (H1N1) 2009 (H1N1pdm09): PaO 2 < 60 mm Hg, hypercapnoea (pCO 2 > 55 mm 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.
The following data were collected from the hospitalized patients: Date and time of admission to hospital/ICU, age, sex, residential status, co-existing conditions, date and time of first symptoms presence and type of influenza syndrome; duration of treatment in hospitals and ICU; duration between the onset of illness and diagnosis; kept on ventilator support; outcome of hospital/ICU admission; time from the onset of illness to death; time from antiviral drug started to death.
All patients' admission history and their medical records were assessed from swine flu ward for initial clinico-epidemiological details and from the 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 the study period. Approval by the institutional review board was not required because of, this infectious disease was covered under epidemic act and state health department  has implemented Epidemic Disease Control Act, 1897 from 18 th August, 2009 and issued a notification that it was in the interest of the public health to collect data on an emerging pathogen.
Laboratory confirmation of infection
The pandemic influenza A (H1N1) 2009 (H1N1pdm09) virus was detected with the use of real-time RT-PCR assay in accordance with the protocol from the US CDC, as recommended by the WHO.  Two swabs from naso-pharynx and one from pharynx were collected from suspected patients and their contacts for detection of pandemic influenza A (H1N1) 2009 (H1N1pdm09) virus by real-time RT-PCR assay.  The test was conducted by using Applied Biosystem PCR machine. The test was conducted by using TaqMan polymerase enzyme (combination of RT and DNA polymerase enzyme) with probe by preparing master mix for testing of influenza A (H1N1). The decision for different clinical and laboratory tests was made by the treating physician.
All data was entered in Kingsoft spreadsheet 2013 (Kingsoft Office Software co. Ltd, USA) and analyzed by using Epi Info software (version 3.5.1) from CDC, Atlanta.  Bivariate analysis was performed using χ2 test or Fisher's exact as appropriate.
| Results|| |
Demographic and clinical characteristics of patients
A total of 511 cases infected with pandemic influenza A (H1N1) 2009 (H1N1pdm09) [Table 1] were diagnosed and hospitalized in different hospitals in Rajkot. Of the 511 cases of pandemic influenza A (H1N1) 2009 (H1N1pdm09), 274 cases reported during the first wave and 237 during the second wave.
Of the 274 cases seen during the first wave, 87 (31.8%) had severe disease and 187 (68.2%) had the non-severe disease [Table 1]. Among the 87 severe disease patients during the first wave, mortality was reported in the majority (81.6%) of patients. During the second wave, there were 53 (22.36%) patients with severe with mortality of 94.3%.
|Table 1: Baseline characteristics of pandemic influenza A (H1N1) 2009 (H1N1pdm09) infected patients in Saurashtra region from September, 2009 to February, 2011 |
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First wave reported severe cases more among adults (>25 years) (69%). More number of children up to 15 years needed intensive care during the second wave (30.2%) compare to the first wave (20.7%). There were significantly higher numbers of patients from an urban area with severe cases during the first wave (P < 0.05) [Table 1]. Second wave was different by reporting significant number of severe cases (P < 0.05). The median duration of diagnosis of infection was 5 days after the onset of illness during both waves.
Majority of patients presented mainly with cough, fever, sore throat and shortness/difficulty in breathing [Table 2]. First wave reported a significant number of patients with severe disease have a presence of the underlying condition than during the second wave. Both waves reported patients with diabetes mellitus, hypertension, chronic pulmonary diseases and pregnancy [Table 2].
|Table 2: Clinical features and co-existing conditions among pandemic influenza A (H1N1) 2009 (H1N1pdm09) infected patients |
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Laboratory and radiological findings
Various laboratory findings including leukopenia, anemia, lymphopenia and thrombocytopenia were reported in patients with severe disease during both the waves [Table 3].
|Table 3: Laboratory and radiological findings of pandemic influenza A (H1N1) 2009 (H1N1pdm09) infected patients* |
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More than half of patients with severe disease (56.3%) during the first wave and 62.3% during the second wave were first treated by general practitioner/physician and then referred to the higher center. For both reported waves, the median time for the hospital stay was 7 days for non-severe cases and 4 days for severe cases. Five days median time from the onset of illness to diagnosis and hospitalization was reported in both waves. Mortality was high (94.3%) among severe cases requiring intensive care during the second wave, compare to the first wave (81.6%).
All patients have received antiviral drug oseltamivir during both waves. During the second wave, 39.6% severe cases received it within 2 days of onset of illness, higher than the first wave (19.5%).
| Discussion|| |
The present study reports hospitalized patients of pandemic influenza A (H1N1) 2009 (H1N1pdm09) belonging to Category C  in Rajkot for two waves - first wave (274 cases) from September 2009 to March 2010 and then second wave (237 cases) from June 2010 to February 2011.
There was no major difference observed between median age of severe disease patients during the first and second waves. Various studies from other countries reported overall higher median age (37-47 years) ,, indicating the involvement of the younger population in the present study. A study from Canada reported a large increase in admissions during the second wave among 45-64 years of age and the smallest increase among school aged children.  Similarly, present study also reports increased admissions during the second wave among 45-64 years age and among school aged children. The reported pattern is consistent with the pattern of influenza transmission in communities from school aged children to the older population. , Additional number of severe cases reported during the second wave among female in the present study. It indicates that adults and females , appear to be at a higher risk of death due to pandemic influenza A (H1N1) virus infection compared to children and teenagers. Severe cases were reported significantly (P < 0.05) during the first wave from an urban area than rural area  which may be due to the dense population in an urban area favoring spread of virus infection.  Second wave reported significant (P < 0.05) cases from a rural area than urban area, may suggest the further spread of infection from urban to a rural area involving new susceptible population.
Median time of 5 days was reported from the onset of illness to diagnosis of pandemic influenza A (H1N1) 2009 (H1N1pdm09) among all the patients during both waves. More than half (56.3%) of the patients during the first wave and 62.3% during the second wave with severe disease were treated first at general practitioner/physician and then referred to higher center. The time duration between the onset of illness and hospital admission and the diagnosis was more than other countries. , The possible justification was that patients seek treatment at the local level from general practitioners and physicians, but with no or little improvement after initial treatment, they were referred to higher center for further investigation and management. Present study reported median time of 4 days for a hospital stay among severe disease patients with 60% patients having less than 5 days hospital stay; compare to 7 days median time and 33% non-severe disease patients. It also indirectly reflects that patients with more severe disease with delayed referral, reaches to higher center at a critical stage. 
Ministry of Health and Family Welfare, Government of India has recommended and supplied oseltamivir to the state governments for distribution in tertiary care centers and district hospitals in adequate quantity and was available in reported region also. In the present study area, all the pandemic influenza A (H1N1) 2009 (H1N1pdm09) infected cases received oseltamivir after hospital admission. During the first wave 19.5% severe disease patients and during the second wave 39.6% received it within 2 days of onset of illness, while in United States, 45% infected patients received oseltamivir within 2 days of onset of illness.  During the second wave, may be due to increased awareness and availability of antiviral drug oseltamivir within the community and hospitals, more severe cases received it within 2 days of onset of illness. When started early, antiviral drug has a beneficial effect. Study reported that patients admitted to ICU or died were less likely to receive such therapy within 48 h after the onset of symptoms. 
Present study reported majority patients in both categories had cough, fever, shortness of breathing and sore throat, likewise patients of other countries. ,, Current study reported 42.5% severe pandemic influenza A (H1N1) 2009 (H1N1pdm09) patients during the first wave and 18.9% severe cases during the second wave have any one co-existing condition, which was 52-74% as reported in other studies. ,,, Study reported no difference according to co-morbidities between survived and died patients,  but the current study reported a significant difference during the first wave. However, second wave did not have such difference. Hypertension and diabetes mellitus were the most common underlying conditions in the patients we studied, followed by chronic pulmonary diseases during both the waves. Several studies reported hypertension, diabetes mellitus and chronic pulmonary diseases as common co-morbid condition. ,, Pregnancy was a well-documented risk factor for severe infection and death in seasonal influenza and in previous pandemics. ,, In this study, pregnancy as a risk factor reported in 11.5% (P < 0.05) severe cases during the first wave and in 7.5% during the second wave.
Pneumonia was reported more during both the waves among patients with severe disease than among non-severe cases. All patients with reported pneumonia on chest radiography received antiviral drug. Similar findings were also reported by several studies. ,, In the present study, 62.1% severe cases received corticosteroids during the first wave (P < 0.05) and 22.6% during the second wave. Various studies reported that early use of corticosteroids in patients with influenza A (H1N1) did not result in better outcomes and may be associated with increased risk of superinfection or lung injury ,, or may prevent progression to severe pneumonia if treated with antiviral drugs.  Further studies are required to determine the effect of corticosteroids on the outcome of a severe pandemic influenza A (H1N1) 2009 (H1N1pdm09) cases.
The data was taken from only hospitalized patients, so patients who become infected in the community and did not go to the hospital were not included in our study. Furthermore, patients belonging to Category B (i) or B (ii) who were treated on an outpatient basis and not being tested were not included in the present 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.
We were also unable to assess factors relating to education level or household size. Considering association between co-existing condition and severity of disease, it is possible that the presence of a co-existing condition that makes ICU admission more likely might also have made ascertainment of virologic infection more likely, thus producing an inflated estimate of any potential association. Analysis as per APACHE score of severe patients kept on mechanical ventilation was not done due to inadequate data availability for same. With regard to present study, the relative impact of the direction of this type of selection bias, known as Berksonian bias, is uncertain. The overall findings may be different during future waves, owing to the timely deployment of an effective vaccine, to viral mutation and resistance to antiviral drugs.
| Conclusion|| |
High mortality was reported during the second wave. More cases reported among younger age group than adults during the second wave. Presence of co-existing conditions was a significant risk factor during the first wave but not so for the second wave. These findings may be different during future waves, owing to the timely deployment of an effective vaccine, to viral mutation and resistance to antiviral drugs.
| Acknowledgements|| |
Authors are thankful to Chief Medical Officer, Civil Hospital, Rajkot and other private hospitals for providing the necessary data. Authors are also thankful to nursing staff of swine flu ward and Medical Record Department of Civil Hospital, Rajkot for helping in providing necessary records and information.
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[Table 1], [Table 2], [Table 3]