A two wave comparison of clinical and epidemiological characteristics of 2009 pandemic Influenza A (H1N1) in hospitalized pediatric patients of Saurashtra region, India Chudasama RK, Patel UV, Verma PB, Patel RR, Amin CD, Buch P

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ORIGINAL ARTICLE

Year : 2013 | Volume : 2 | Issue : 3 | Page : 207-213

A two wave comparison of clinical and epidemiological characteristics of 2009 pandemic Influenza A (H1N1) in hospitalized pediatric patients of Saurashtra region, India

Rajesh K Chudasama¹, Umed V Patel¹, Pramod B Verma¹, Ravikant R Patel¹, Chikitsa D Amin¹, Pankaj Buch²
¹ Department of Community Medicine, Pandit Deendayal Upadhyay Medical College, Rajkot, India
² Pediatrics Department, M P Shah Medical College, Jamnagar, Gujarat, India

Date of Web Publication

14-Feb-2014

Correspondence Address:
Rajesh K Chudasama
Vandana Embroidary, Mato Shree Complex, Sardar Nagar Main Road, Rajkot - 360 001, Gujarat
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/2278-0521.127072

Abstract

Objective: To study and compare clinical and epidemiological characteristics of pediatric patients hospitalized with 2009 pandemic Influenza A (H1N1) infection during two waves. Materials and Methods: From September 2009 to February 2011, 62 children were admitted in pediatric ward of the hospitals during 1 ^st wave and 55 during 2 ^nd wave, infected with 2009 Influenza A (H1N1) virus in Rajkot city. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm infection. The clinico-epidemiological features of the disease were closely compared and monitored. Results: First wave reported median age of 2.5 years, which was 2 years during second wave in positive cases. The median duration of diagnosis of infection was reported 5 days after onset of illness, and 7-day median time for hospital stay in both the waves. Majority of patients reported with cough and fever. Total 16.1% patients during 1 ^st wave and 27.3% in 2 ^nd wave reported some underlying condition. All admitted patients received oseltamivir drug, but only 9.7% (1 ^st season) and 12.7% (2 ^nd season) cases received it within 2 days of onset of illness. In both seasons, more than one-fourth (29.0%) of admitted patients expired. Pneumonia was reported in 97.1% patients (1 ^st wave) and in 60.0% (2 ^nd wave) with chest radiography. Conclusion: Influenza A (H1N1)-related illness affects children, including infants with survival of about 71% patients during both waves. The median time from the onset of illness to diagnosis was 5 days. Delayed referral, presence of any coexisting condition, pneumonia and receiving corticosteroid treatment were associated with severe Influenza A (H1N1).

Keywords: Antiviral drug, pediatric group, epidemiology, Influenza A (H1N1), reverse-transcriptase-polymerase-chain-reaction (RT-PCR)

How to cite this article:
Chudasama RK, Patel UV, Verma PB, Patel RR, Amin CD, Buch P. A two wave comparison of clinical and epidemiological characteristics of 2009 pandemic Influenza A (H1N1) in hospitalized pediatric patients of Saurashtra region, India. Saudi J Health Sci 2013;2:207-13

How to cite this URL:
Chudasama RK, Patel UV, Verma PB, Patel RR, Amin CD, Buch P. A two wave comparison of clinical and epidemiological characteristics of 2009 pandemic Influenza A (H1N1) in hospitalized pediatric patients of Saurashtra region, India. Saudi J Health Sci [serial online] 2013 [cited 2023 Mar 22];2:207-13. Available from: https://www.saudijhealthsci.org/text.asp?2013/2/3/207/127072

Introduction

A novel swine origin Influenza A (H1N1) virus has become 21 ^st century's first pandemic. ^[1] The new Influenza virus of H1N1 strain underwent triple reasserting and contains genes from avian, swine, and human viruses. ^[2],[3] In early April 2009, cases of human infection with 2009 pandemic Influenza A (H1N1) virus were identified in the Mexico ^[4] and then in United States (US). ^[5] The World Health Organization (WHO) raised the pandemic level from five to six, which was the highest level after 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. ^[6],[7] The first confirmed case of Influenza A (H1N1) infection in India was documented in May, 2009. ^[8] Saurashtra region is a western most part of Gujarat state in India. Gujarat state reported first H1N1 positive confirmed case during June 2009 ^[9] and in Saurashtra region during August 2009. ^[10] The symptoms of 2009 H1N1 Influenza were expected to be similar to the symptoms of regular human seasonal Influenza, including fever, cough, sore throat, and myalgia. ^[11] The objective of present study is to compare clinical and epidemiological characteristics of confirmed pediatric cases of 2009 pandemic Influenza A (H1N1) virus infection admitted in various hospitals of Rajkot city. The study included two waves of Influenza A (H1N1)-first wave from September 2009 to February 2010 (reported 62 cases) ^[12] and second wave from August 2010 to February 2011 (reported 55 cases).

Materials and Methods

Data sources and study period

From the first reported case of Influenza A (H1N1) in May 2009 in India, the Central Government started preparation regarding the management of infected patients. Gujarat state, including Saurashtra region, had started monitoring and surveillance activities as soon as the positive cases were reported from August 2009 onwards. Due to availability of all treating facilities, including intensive and ventilator support, state government established 80 beds swine flu isolation ward in Pandit Dindayal Upadhyay (PDU) Medical College and Civil Hospital at Rajkot city for admission of suspected/confirmed patients for diagnosis, treatment, and monitoring. Total 117 pediatric patients found positive and admitted by Pediatric Department of Civil Hospital and two other pediatric hospitals of Rajkot city from September 2009 to February 2011 were included for analysis. The first wave from September 2009 to February 2010 reported 62 patients and second wave from August 2010 to October 2010 reported 55 patients. Though no pediatric case was reported from November 2010, surveillance was continued up to February 2011.

Categorization of Influenza A (H1N1) cases

Ministry of Health and Family Welfare, Government of India issued guidelines ^[13] for categorization of Influenza A (H1N1) cases during screening for home isolation, testing treatment, and hospitalization [Table 1]. Different categories were defined including 1) category A, 2) category B (1), 3) category B (2), and 4) category C. Patients were monitored or treated in first three category, while patients belonging to category C were hospitalized and treated. In the present study, total 117 pediatric patients belonging to category C were tested, confirmed, hospitalized, monitored and included in the analysis.

Table 1: Baseline characteristics, disease history, and outcomes of hospitalized children infected with 2009 pandemic Influenza A (H1N1) virus in Saurashtra region

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Clinical case/suspected case definition ^[7]

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 7 days or an 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. 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.

Data variables, records, and analysis

Several types of data were collected from the pediatric patients and their records: Date and time of admission to hospital/intensive care units (ICU), age sex, religion, residential status, co-existing conditions, date and time of first symptoms, and various others from medical record and statistics department of different hospitals. The children were grouped into two categories as (1) severe Influenza A (H1N1) cases-those who needed intensive care or died, and (2) non severe Influenza A (H1N1) cases-those who don't need intensive care and survived. ^[14] For intensive care, following signs were used by treating pediatricians- PAO ₂ <<sub> 60 mmHg, hypercapnia (PCO ₂ > 55 mmHg, 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.

Line list number was given to every patient to avoid duplication at any time during the study period. We made no assumptions regarding missing data; all proportions were calculated as percentages of the patients with available data. Ethical clearance and approval by an institutional review board were not required because this infectious disease was covered under epidemic act and state health department ^[15] has implemented Epidemic Disease Control Act, 1897 from August 18, 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 viral infection

The 2009 H1N1 virus was detected with the use of a real time RT-PCR assay in accordance with the protocol from the US centers for Disease Control and Prevention, as recommended by the WHO. ^[16] Person suspected of being infected and persons identified as close contacts were investigated by taking two swabs from naso-pharynx and one from pharynx for detection of virus by a real time RT-PCR assay, as per. ^[13] The test was conducted 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 a master mix for testing of Influenza A (H1N1). The decision for different clinical and laboratory tests was made by the treating pediatrician.

Statistical analysis

For categorical variables, the percentages of patients in each category and median time of various variables were calculated and appropriate statistical test (Chi-square test or Fisher's exact test) was applied. We calculated descriptive statistics for all study variables. All data was entered in MS Excel, and analyzed by using Epi Info software (version 3.5.1) from Centers for Disease Control and Prevention (CDC). ^[17]

Results

Demographic and clinical characteristics

Total 62 pediatric cases from September 2009 to February 2010 and 55 cases from August 2010 to February 2011 were infected and hospitalized with 2009 H1N1 Influenza A [Table 1] in pediatric ward of different hospitals in Rajkot. Positive cases were reported from the Rajkot city (40.3%), Rajkot district (29.0%), and from other districts (30.6%) of Saurashtra region during first season compare to 29.1% in Rajkot city and 34.5% in Rajkot district during second season [Table 1].

Month-wise distribution [Figure 1] of Influenza A (H1N1) infected patients in Saurashtra region showed that during first wave, number of cases increased from November 2009 (16) to January 2010, with highest cases during December 2009 (31). In second wave, cases were reported from August 2010 up to October 2010.

Figure 1: Month wise distribution of hospitalized children infected with Influenza A (H1N1) from September 2009 to February 2011 in Saurashtra region

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The median age of 2.5 years was reported during 1 ^st wave and 2 years during 2 ^nd wave. The median duration of diagnosis of infection was 5 days after the onset of illness during both the seasons. During second wave, patients mainly reported cough, fever, shortness/difficulty in breathing, and sore throat [Table 2]. Presence of co-existing condition reported in 15 (27.3%) cases during 2 ^nd season compare to 10 (16.1%) in 1 ^st season. Patients reported with seizure disorder, thalassemia, anemia, and mainly asthma.

Table 2: Clinical features and coexisting conditions of Influenza A (H1N1)-infected hospitalized children in Saurashtra region

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Laboratory and radiographic findings

Leukopenia was observed in 22.8% of patients in first wave compare to 6.1% in second wave [Table 3]. Anemia was reported in more than three fourth children during both the waves. Anemia was defined according to WHO criteria of a hemoglobin level <11 gm/dl in children. It was further classified into categories of mild anemia (10-10.9 gm/dl), moderate anemia (8-9.9 gm/dl), and severe anemia (<8 gm/dl). Thrombocytopenia was found in 22.4% cases during 1 ^st wave and 27.9% in 2 ^nd wave. Chest X-ray was done in 54.8% cases during first season, which was increased to 72.7% during second season. However, pneumonia was reported more among those undergone for chest X-ray, during first season (97.1%) than in second season (60.0%).

Table 3: Laboratory and radiographic findings on hospital admission in Influenza A (H1N1)-infected children in Saurashtra region*

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Treatment outcome

For both the seasons, median time for hospital stay was 7 days for Influenza A (H1N1)-infected children. Duration of hospital stay 6 days or more was observed in 35 (63.6%) patients during second season. All admitted patients received antiviral drug oseltamivir [Table 1] during both waves, but only 9.7% cases during 1 ^st wave and 12.7% during 2 ^nd wave received it within two days of onset of illness. After hospital admission, about 71% cases survived and discharged during both the waves, while 29% cases died even after receiving treatment, including antiviral drugs and life-saving support.

Children with severe Influenza A (H1N1) were more likely to have cough, fever, shortness of breath, presence of coexisting conditions, pneumonia on chest radiography on admission, receiving corticosteroids [Table 4] than non severe cases. Statistical significance was not found when comparison was made regarding under 5 year age group, initiation of antiviral treatment within 2 days of onset of illness, among severe Influenza A (H1N1) patients.

Table 4: Two wave comparison of characteristics of non severe and severe Influenza A (H1N1) hospitalized pediatric patients in Saurashtra region, India

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Discussion

The 2009, Influenza A (H1N1) pandemic was reported in Saurashtra region in two distinct waves. Present study reports all pediatric patients with confirmed 2009 Influenza A (H1N1) belonging to category C, ^[13] who were hospitalized in Rajkot, including two waves from September 2009 and February 2011. Major difference of affected age groups was not reported during both the waves compared to the other. ^[18] Large study population affected during 1 ^st wave belonged to urban area but during 2 ^nd wave mainly affected population was from blocks and rural area. These findings may be because of development of immunity among urban population during 1 ^st wave exposure and spread of virus to blocks and rural area during second wave.

The median age of pediatric patients was 2.5 years during 1 ^st wave and 2 years in 2 ^nd wave, which was lower than similar studies reported from Canada (4.8 yrs) ^[19] and Argentina (10 yrs). ^[20] The median time for hospital stay was 7 days during both the waves in the present study (range < 1 day-30 days), compare to 4 days (range 2-7 days) in Canada ^[21] and 8.1 days (range 6-16 days) in China. ^[22] For both the waves, 5 days median time interval from the onset of illness to hospital admission and diagnosis of infection was reported compared to 4 days in Argentina. ^[19] In present the study, almost all children died during both waves, after 5 days of illness compared to 3 days in Influenza-associated deaths reported in US. ^[23]

Current interim CDC guidelines for pandemic and seasonal Influenza recommend the use of either oseltamivir or zanamivir for hospitalized patients with suspected or confirmed Influenza and for outpatients who are at high risk for complications. ^[24] 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 the reported region also. ^[25] In the present study, all the Influenza A (H1N1)-infected children received oseltamivir after hospitalization but only 9.7% cases during 1 ^st wave and 12.7% during 2 ^nd wave received it within 2 days of the onset of illness, like in Argentina (12%). ^[20] Underutilization of oseltamivir inspite of its free availability was reported in neighbor country like Bangladesh. ^[26] Early initiation of oseltamivir administration after symptom onset significantly reduced occurrence and severity of pneumonia and shortened hospitalization due to pandemic Influenza A (H1N1). ^[27],[28] Initial primary treatment by general practitioners or pediatrician, delayed referral to higher center and investigation, inadequate knowledge about the Influenza A (H1N1) among general population, may be possible explanations for a delayed start of oseltamivir in suspected or confirmed Influenza A (H1N1) patients. ^[29] Under an Emergency Use Authorization in US, oseltamivir therapy was recommended for 2009 H1N1 infection even if it was initiated more than 48 hours after the onset of illness and also approved its use in children under the age of 1 year. ^[30]

Month-wise distribution of Influenza A (H1N1)-infected patients in Saurashtra region showed that during first wave, number of cases increased from November 2009 (16) reached highest (31) in December 2009 and then fell to 9 in January 2010. ^[31] In second wave, cases reported from August 2010 up to October 2010. The atmospheric temperature remains lowest in December, correlating increase in the reported number of infected patients with Influenza A (H1N1). It was continued in January and February. By the end of February, no positive case was reported from study area. It signifies the Influenza virus relationship with cold as the maximum number of cases occurred during months of winter season, as also reported by other studies. ^[32],[33] The monsoon season starts from July and ends by October every year. The second wave reported cases during this monsoon season from August to October, which may suggest that high humidity may favor the spread of infection during monsoon. Further studies may provide some more information about it.

Likewise, in patients from other countries and within a country, ^{[20],[21],[34],[35],[36]} majority of patients reported cough and fever, though cases were reported more with such complaints during second wave. The patients reported with low prevalence (16.1% in 1 ^st wave and 27.3% in 2 ^nd wave) of underlying medical conditions than in United States (67%-73%), ^[33],[37] Turkey (56%), ^[38] and Argentina (35%). ^[20] Various studies reported that, 44 to 84% of patients hospitalized with seasonal Influenza had an underlying condition ^[30],[39] and our reported prevalence is even less than the reported studies.

Leukopenia found in 22.8% cases during first wave, which was reduced to 6.1% during second wave; 18.5% and 16.7% children with lymphopenia during first season and second season respectively, which was higher than patients in Argentina. ^[20] Laboratory investigations were clinically driven. It was not possible to check for other pathogens among the study patients due to limited resources. Risk of mortality may be aggravated by other co infections. Significant number of patients with severe Influenza A (H1N1) reported pneumonia (P < 0.05) on chest radiography during 1 ^st and 2 ^nd wave. All hospitalized children with evidence of pneumonia received antibiotics and antiviral drugs, similar to other countries. ^[33],[40] In the 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. ^[41] In the present study, significant number of children with severe Influenza A (H1N1) received corticosteroids (P < 0.05) after hospitalization during both the seasons. 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. ^{[42],[43],[44]}

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. ^[45]

Our study also has some limitations. The data was taken from only hospitalized children, so patients who become infected in the community and did not go to the hospital were not included in our study. Also, patients belonging to category B (i) or B (ii), who were treated on outpatient basis and not being tested, were not included in present study. All diagnostic testing was clinically driven, and other investigations were not obtained in a standardized fashion. Few investigations were not done like Creatine Phosphokinase (CPK), C-reactive Protein (CRP), Respiratory Syncitial Virus (RSV) as the kits were not available in the study institute for same. 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

Influenza A (H1N1)-related illness affects children, including infants, with survival of about 71% patients during both waves. The median time from the onset of illness to virus detection with use of real-time RT-PCR was 5 days. Delayed referral, presence of any coexisting condition, pneumonia, and receiving corticosteroid treatment were associated with severe Influenza A (H1N1).

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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