|Year : 2012 | Volume
| Issue : 3 | Page : 158-165
Clinical and epidemiological features among hospitalized patients of pandemic influenza A (H1N1) in Saurashtra region, India: A two wave comparison
Rajesh K Chudasama1, Umed V Patel2, Pramod B Verma2, Ravikant R Patel2, Priyanka K Patel3
1 Department of Community Medicine, M. P. Shah Medical College, Jamnagar, India
2 Department of Community Medicine, P. D. U. Medical College, Rajkot, Jamnagar, India
3 Department of Microbiology, M. P. Shah Medical College, Jamnagar, India
|Date of Web Publication||26-Dec-2012|
Rajesh K Chudasama
Vandana Embroidery, Mato Shree Complex, Sardar Nagar Main Road, Rajkot, Gujarat
Source of Support: None, Conflict of Interest: None
Objective: To study and compare clinical and epidemiological characteristics of patients who were hospitalized with influenza A (H1N1) infection for two waves in Saurashtra region. Materials and Methods: Total 274 patients admitted during the first wave from September 2009 to March 2010 and 237 during the second wave from June 2010 to February 2011 with 2009 influenza A (H1N1) virus were admitted in different hospitals in Rajkot city. Real-time reverse-transcriptase-polymerase-chain-reaction (RRRT-PCR) testing was used to confirm infection; the clinical and epidemiological features of the disease were closely monitored. Results: The median age of positive cases reported was 27 years in the first wave and 29 years in the second wave, respectively. The median duration of diagnosis of infection was reported five days after onset of illness in both the waves. Majority of patients were reported with cough and fever. Total 160 patients were reported with at least one underlying condition. Hypertension and diabetes mellitus either alone or together was mainly reported as the underlying condition during both season, followed by chronic pulmonary diseases and pregnancy. More number of pregnant women were reported with a range of 5 to 9 months of amenorrhea during first wave (5.5%) compare to second wave (3.0%). Conclusion: We have demonstrated that during two waves, infection-related illness affects both children including infants and adults with survival of 77.2% patients in second wave. Pregnancy was found as a significant (P < 0.05) risk factor for severe disease. Significant number of patients with severe influenza A (H1N1) received antiviral treatment within two days of onset of illness.
Keywords: Clinical features, epidemiology, influenza A (H1N1), RT-PCR, antiviral drug, intensive care
|How to cite this article:|
Chudasama RK, Patel UV, Verma PB, Patel RR, Patel PK. Clinical and epidemiological features among hospitalized patients of pandemic influenza A (H1N1) in Saurashtra region, India: A two wave comparison. Int J Health Allied Sci 2012;1:158-65
|How to cite this URL:|
Chudasama RK, Patel UV, Verma PB, Patel RR, Patel PK. Clinical and epidemiological features among hospitalized patients of pandemic influenza A (H1N1) in Saurashtra region, India: A two wave comparison. Int J Health Allied Sci [serial online] 2012 [cited 2020 Apr 8];1:158-65. Available from: http://www.ijhas.in/text.asp?2012/1/3/158/105079
| Introduction|| |
In April 2009, pandemic influenza A (H1N1) 2009 virus emerged in Mexico  and United States.  Very soon the virus spread to other countries of the world, which lead World Health Organization (WHO) to raise 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 its first pandemic influenza A (H1N1) case during May, 2009,  but large numbers of cases were reported after the August, 2009.  From Gujarat state in India, first H1N1 positive confirmed case was reported in June 2009. Saurashtra region is a western part of Gujarat state, reported first case in August 2009.  All patients with confirmed infection were quarantined in isolation ward to prevent spread in the general population.
Influenza pandemic has created tremendous hardship on already overburdened health system in developing nations but unprecedented surveillance has also provided opportunity to study different epidemiological parameters including disease severity of influenza viruses in country like India. There are many studies reported worldwide for first wave of the 2009 pandemic influenza A (H1N1) and very few studies reported second wave findings. ,, The present study summarizes the clinical and epidemiological characteristics of confirmed cases of 2009 pandemic influenza A (H1N1) virus infection, hospitalized in various hospitals of Rajkot city of Saurashtra region from September 2009 to February 2011. The study covers two waves of pandemic influenza A (H1N1) - first wave from September 2009 to March 2010 and second wave from June 2010 to February 2011.
| Materials and Methods|| |
During the study period, total 511 patients found positive for pandemic influenza A (H1N1) and admitted in different hospitals of Rajkot from 1 st September, 2009 to 28 th February, 2011 combining two waves were included for analysis. The first wave from September 2009 to March 2010 reported 274 confirmed cases and second wave from June 2010 to February 2011 reported 237 confirmed cases of 2009 pandemic influenza A (H1N1). Though cases were not reported from November, 2010 onwards, the surveillance was continued up to February 2011.
Categorization of Influenza A (H1N1) cases:  Ministry of Health and Family Welfare, Government of India had issued guidelines for categorization of influenza A (H1N1) cases during screening for home isolation, testing treatment and hospitalization. Current report describes 274 patients of first wave and 237 of second wave belonging to category C who were tested and confirmed, hospitalized, monitored and included in the analysis.
Clinical case/suspected case definition:  A suspected case was defined as an influenza like illness (temperature >37.5°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 in the previous seven days or an epidemiologic link to a person with confirmed or suspected infection in the previous seven days. A confirmed case was defined by a positive result of a real-time reverse-transcriptase-polymerase-chain-reaction (RRRT-PCR) assay performed at a laboratory operated under the auspices of the state government, run under Microbiology department, P D U Medical College, Rajkot. A close contact was defined as a person who lived with or was exposed to the respiratory secretions or other bodily fluids of patients with suspected or confirmed influenza A (H1N1) infection.
Several types of data collected from the patients, including socio-demography, any coexisting conditions, regarding onset of illness and treatment, were taken. Data regarding hospitalization, whether intensive care needed, duration of antivirus drug and disease outcome were collected from medical records and statistics departments of various hospitals.
Data collection and analysis were coordinated by the Community Medicine Department, P D U Medical College, Rajkot. All admitted patients' admission history and their medical records were assessed from swine flu ward for initial clinical and epidemiological details and from medical records and statistics departments after patient discharge/death from Civil Hospital and various other private hospitals of Rajkot city. Line list number was given to every patient to avoid duplication at any time during study period. We made no assumptions regarding missing data; all proportions were calculated as percentages of the patients with available data. Approval by institutional review board was taken. 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 2009 H1N1 virus was detected with the use of a real-time RRRT-PCR assay in accordance with the protocol from the US centers for Disease Control and Prevention, as recommended by the WHO.  Two swabs from nasopharynx and one from pharynx were collected from suspected patients and their contacts for detection of influenza A (H1N1) virus by real-time RRRT-PCR assay by using Applied Biosystem PCR machine. The test was conducted by using TaqMan polymerase enzyme (combination of reverse transcriptase and DNA polymerase enzyme) with probe by preparing master mix for testing of influenza A (H1N1).
Continuous variables were summarized as means (+SD). For categorical variables, the percentages of patients in each category were calculated and appropriate statistical test (Chi-square test) was applied when required. We calculated descriptive statistics for all study variables. All data was entered in MS Excel and analyzed using Epi Info software (version 3.5.1) from CDC. 
| Results|| |
Demographic and clinical characteristics of patients
During first wave from September 2009 to March 2010, total 274 patients were diagnosed with pandemic influenza A (H1N1) and admitted in the hospital, while during second wave from June 2010 to February 2011, total 237 patients were diagnosed and admitted [Table 1]. Positive cases were reported mainly from Rajkot city (40.9%), followed by Rajkot district (28.6%), while 30.5% cases were from other seven districts of Saurashtra region during the first wave. During second wave, more cases were reported from Rajkot district (30.8%) and other districts (36.3%).
|Table 1: Two wave comparison of baseline characteristics, disease history, and outcomes of patients infected with 2009 pandemic influenza A (H1N1) virus in Saurashtra region, India|
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First wave reported median age of 27 years, which was little more (29 years) during second wave in positive cases. However, the median duration of diagnosis of infection was reported five days after onset of illness (1-28 days range) in both the waves. During both the waves, majority of patients reported with cough, fever followed by other complaints like shortness/difficulty in breathing, sore throat and nasal catarrh [Table 2]. Total 160 patients reported at least one underlying condition during the whole study period, including 90 patients during first wave and 70 during second wave. Hypertension and diabetes mellitus either alone or together were mainly reported as the underlying condition during both season, followed by chronic pulmonary diseases, pregnancy, chronic heart diseases and seizure diseases [Table 2]. More number of pregnant women were reported with a range of 5 to 9 months of amenorrhea during first wave (5.5%) compare to second wave (3.0%).
|Table 2: Clinical features and coexisting conditions of influenza A (H1N1) infected patients in Saurashtra region, India|
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Laboratory and radiographic findings
Leukopenia was observed in 25% patients during first wave compared to 16% during the second wave [Table 3]. More cases of mild-to-moderate anemia were reported during second wave. Lymphopenia was reported more during first season of influenza A (H1N1). During second wave, chest x-ray was done in 95% patients compared to 83% in first wave. Patients with pneumonia were reported more during the first wave (93%).
|Table 3: Laboratory and radiographic findings on hospital admission in influenza A (H1N1) infected patients*|
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During both the waves, the median time for hospital stay was six days for influenza A (H1N1) patients. All the reported positive patients had received antiviral drug oseltamivir [Table 2] during both the waves, though 16.1% patients received it within two days of onset of symptoms in first wave compared to 13.5% in second wave. The survival rate was more during second wave (77.2%) with mortality of 22.8% compared to first wave mortality (25.9%) after receiving treatment including antiviral drugs and life-saving support.
Age 15 years or less, presence of any one coexisting condition, pregnancy, radiologically confirmed pneumonia on admission during first wave, while receiving antiviral treatment within two days of onset of symptoms during second wave, were significantly associated (P < 0.05) with severe influenza A (H1N1) patients who needed either intensive care or died then among non-severe cases [Table 4].
|Table 4: Two wave comparison of characteristics of non-severe and severe influenza A (H1N1) hospitalized patients in Saurashtra region, India|
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| Discussion|| |
The 2009 influenza A (H1N1) pandemic occurred in Saurashtra region as two distinct waves. The study reports two waves of 2009 pandemic influenza A (H1N1) - first wave from September 2009 to March 2010 and then second wave from June 2010 to February 2011. Cases were not reported from December 2010 onwards but the surveillance was continued up to February 2011. This study reports total 511 patients (274 in first wave and 237 in second wave) with confirmed 2009 influenza A (H1N1) belonging to category C,  who were hospitalized in various super specialty hospitals in Rajkot from September 2009 to February 2011. The median age of patients was 27 years during first wave, which was 29 years during second wave indicating little change in affected age. Significant association was found for severe influenza A (H1N1) and age 15 years or less during first wave like others ,, but not during second wave. Present study reported only 0.2% patients having history of travel to infected origin country during first wave compared to other (76.5%). 
Present study reports no major difference of affected age groups during both the waves compared to other.  The majority of population affected during first wave was of urban area but during second wave mainly affected population was from blocks and rural areas. These findings may be because of development of immunity among urban population during the first wave exposure and spread of virus to blocks and rural areas during the second wave.
The median time of hospitalization from admission to discharge or death was six days (range <1 to 52 days) during both waves. Present study reported five days median time interval during two waves, more than in other countries, , from onset of illness to diagnosis of infection and hospital admission. The possible justification for that is patients from rural areas and small town areas were initially treated at local level by general practitioners, but with no or little improvement after initial treatment and later they were referred to higher center.
Most of 2009 H1N1 viruses were susceptible to two neuraminidase inhibitors, oseltamivir and zanamivir, and resistant to two adamantines, amantadine and rimantadine, as tested and reported by CDC to date.  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 during both the waves. Although the evidence of benefit from antiviral therapy is strongest when treatment is initiated within 48 h after the onset of illness, a study with oseltamivir in hospitalized patients reported reduction in mortality even after 48 h of onset of illness.  In present study area, all the influenza A (H1N1) infected patients received oseltamivir as one capsule containing 75 mg oseltamivir, twice a day for five days after hospital admission, but in first wave only 14.9% had received it within two days of onset of illness, which was even reduced to 13.5% during the second wave (P < 0.05). Underutilization of oseltamivir in spite of its free availability was reported in neighboring country like Bangladesh.  When initiated early, use of antiviral drug is beneficial, since critical patients were less likely to receive such therapy within 48 h after the onset of symptoms,  while our study suggest about 40% mortality even after complete course of oseltamivir therapy, possibly because of delayed referral and initiation of antiviral drug and also underutilization of drug. 
Month-wise distribution shows two different waves-first wave from September 2009 to March 2010 and second wave from June 2010 to November 2010 [Figure 1]. During first wave, number of cases increases rapidly from December 2009 onwards. Highest positive cases (124) were reported during January, followed by decline up to March 2010. Cases reported were nil to few from March to July, 2010. The atmospheric temperature remains lowest in December and January, correlating to the increase in reported number of infected patients with influenza A (H1N1). It signifies the relationship between influenza virus and cold season, as maximum number of cases occurs during these months of winter season. ,
|Figure 1: Month-wise distribution of infected influenza A (H1N1) cases for two waves from, September 2009 to February 2011 in Saurashtra region|
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Second wave starts during June 2010 and reports 71 cases in August, followed by 113 in September, which then decreases to 3 by November 2010. No cases were reported thereafter. The second wave was started in monsoon season, suggesting high humidity may favor the spread of influenza A (H1N1). Further studies are needed to prove the association.
All through both the waves' majority of the patients reported cough and fever similar to other countries. ,,, Our study reported underlying medical conditions as 32.8% prevalent during the first wave and 29.5% during the second wave like other,  but lower than in US (73%),  with a range of 52 to 74% as reported in other studies. ,, Hypertension (10.4%) and diabetes mellitus (9.4%) were the most common underlying conditions in the patients we studied during first wave, followed by chronic obstructive pulmonary diseases (4.3%). Several studies reported hypertension, diabetes mellitus and chronic pulmonary diseases as common co-morbid condition. ,,
The 5.5% prevalence of pregnancy (P < 0.05) during first wave in this study was higher than the expected prevalence in the general population (1%),  which was lower than that reported in New Zealand (11%)  and Lithuania (26%).  Pregnancy as a risk factor is more strongly associated (P < 0.05) with severe disease than non-severe influenza. During periods of seasonal influenza and past pandemics, pregnant women have been at higher risk for influenza associated morbidity and mortality. , Significant number of patients with severe influenza A (H1N1) reported pneumonia (P < 0.05) on chest radiography during first wave, received antiviral drugs and antibiotics. Similar findings were also reported by other studies. , In the absence of accurate diagnostic methods, patients who are hospitalized with suspected influenza and lung infiltrates on chest radiography should be considered for treatment with both antibiotics and antiviral drugs. 
Planning for continued pandemic H1N1 transmission and for future influenza pandemics should consider the vulnerability of immunologically naïve urban and rural populations. To identify these populations, surveillance system must provide sufficient coverage and geographic detail to detect local and regional outbreaks and changes in influenza activity. Identifying communities and subpopulations that escaped substantial impact during a pandemic wave should be as important to public health planning as identifying those that were severely affected.  Whether continued transmission of pandemic H1N1 will be associated with another wave of infection or with more typical seasonal transmission is currently unknown. Because of changing characteristics and impacts of successive influenza pandemic waves, comprehensive surveillance is necessary to guide influenza vaccination efforts and pandemic response planning, thereby reducing the morbidity and mortality associated with 2009 pandemic influenza A (H1N1) and future influenza pandemics.
The data was taken only from hospitalized patients for both the waves of influenza A (H1N1). Patients belonging to category B, treated on outpatient basis and not being tested, were not included. 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. The findings may be different during future waves, owing to the timely deployment of an effective vaccine, to viral mutation, and to resistance to antiviral drugs.
| Conclusion|| |
We have demonstrated that during two waves, infection-related illness affects both children including infants and adults with survival of 77.2% patients in second wave. The median time from onset of illness to virus detection with use of real-time RRRT-PCR is five days. Pregnancy was found as a significant (P < 0.05) risk factor for severe disease. Significant number of patients with severe influenza A (H1N1) received antiviral treatment within two days of onset of illness.
| Acknowledgments|| |
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], [Table 4]