|
Indian Pediatr 2011;48:
373-378 |
|
Clinical Profile and Outcome of Swine Flu in
Indian Children |
Rashmi Ranjan Das, Abdus Sami, Rakesh Lodha, Richa Jain, S Broor*, S
Kaushik*, BB Singh*,
M Ahmed*, Rachna Seth And Sushil K Kabra
From the Departments of Pediatrics and *Microbiology, All
India Institute of Medical Sciences, New Delhi 110029, India.
Correspondence to: Dr SK Kabra, Department of Pediatrics,
All India Institute of Medical Sciences,
New Delhi 110029, India.
Email: [email protected]
Received: February 08, 2010;
Initial review: February 24, 2010;
Accepted: May 3, 2010.
Published online. 2010 August 1.
PII: S097475590900125-1
|
Objective: To describe the clinical characteristics and outcome
of Indian children infected with 2009 H1N1 influenza virus.
Study design: Retrospective chart review.
Setting: Outpatient department and hospitalized
patients in a tertiary care hospital.
Methods: Clinical details of 85 children
(positive for the 2009 H1N1 virus infection tested by real-time
reverse-transcriptase–polymerase-chain-reaction assay) were analyzed from
medical charts.
Results: Of the 85 (55 boys) children positive for
2009 H1N1 virus infection, 64.7% were between 5 years to 16 years, and
35.3% were below 5 years age. The mean age of these children was 7.5±3.5
yr. Contact history was positive only in 22 (26%) cases. High grade fever
was the most common symptom, followed by cough and rhinorrhea. Twenty-nine
(34%) patients had an underlying co-morbid condition. Of the 34 patients
who underwent chest radiography during evaluation, 18 children (52.9%) had
findings consistent with lower respiratory tract infection. Antiviral
therapy was initiated in 76 patients. Hospitalization was required in 30
(35.3%) children. Risk factors for hospitalization included underlying
co-morbid condition, respiratory distress, vomiting, wheezing, diarrhea,
hypotension and infiltrates/consolidation on chest radiograph. Mean length
of hospitalization was 131+76 hours, irrespective of underlying
disease. Three children developed Acute Respiratory Distress Syndrome and
died.
Conclusions: Clinical features and routine
laboratory investigations in children with swine origin influenza were
non-specific. Children with co-morbid condition, respiratory distress,
vomiting, wheezing, diarrhea, hypotension and infiltrates/consolidation on
chest radiograph were at higher risk of hospitalization.
Key words: Acute lung injury, ARDS, H1N1
influenza, Pandemic influenza, Swine origin influenza.
|
Swine origin influenza has become the first
pandemic of the 21st century [1]. The currently circulating strain of
swine origin influenza virus of the H1N1 strain has undergone triple
reassortment and contains genes from the avian, swine and human viruses
[2,3]. It is believed to be a legacy of the influenza pandemic of
1918-1919 the virus having adapted over the last 91 years and has now
acquired the ability to not only infect but also spread within the human
host [4]. The symptoms of 2009 H1N1 influenza are expected to be similar
to the symptoms of regular human seasonal influenza and include fever,
cough, sore throat and myalgia. A feature seen more frequently with 2009
H1N1 influenza is gastrointestinal upset with almost a quarter of patients
presenting with vomiting and diarrhea [1,5].
The epidemic of 2009 H1N1 influenza is spreading
rapidly in the Indian subcontinent with more than 23727 cases and 782
deaths [6]. There have been sporadic reports about swine flu in pediatric
population [7-9]. We hereby share our experience with 2009 H1N1 influenza
in children seen between August and December 2009.
Methods
We conducted a retrospective chart review of patients
who were seen at our hospital from August to December 2009. Eligible
patients were infants and children under the age of 16 years who were
admitted to pediatric wards and intensive care unit (ICU) with a diagnosis
of acute respiratory infection or fever; all such eligible children were
tested for influenza viruses. In the out-patient department, children
under the age of 16 years presenting with features of acute respiratory
infection or fever were screened; children of the hospital employees
underwent testing for influenza viruses in our center, while other
children were referred to the government designated centers for the
diagnostic test as per the government guidelines. The diagnosis of 2009
H1N1 influenza was confirmed by testing of combined nasal and throat swabs
with the use of a real-time reverse transcriptase polymerase chain
reaction (RT-PCR) assay. Children were treated with oseltamivir as per the
available guidelines issued by the Ministry of Health, Government of
India, which were periodically revised [10]. In children presenting with
mild symptoms, the medication was administered if the RT-PCR assay
confirmed the diagnosis. In children who were admitted with a suspicion of
swine flu, medication was started after sending the sample for the RT-PCR
test for 2009 H1N1 influenza; it was continued in those who tested
positive.
The study was conducted as a retrospective analysis of
de-identified data. We obtained demo-graphic, clinical, laboratory,
epidemiologic, and radiologic data from a chart review. Hypoxemia was
defined as an oxygen saturation of less than 93% while the patient was
breathing ambient air.
Statistical analysis: The data were managed on
Microsoft Excel and analyzed on Stata 9.0 (Stata Inc, College Station,
TX). The chi-square test or Fisher’s exact test was used to assess the
statistical significance of differences in categorical variables, and the
Wilcoxon ranksum test was used to compare continuous variables. A P
value of less than 0.05 was considered to indicate statistical
significance.
Results
Of the 260 children tested, a total of 85 (55 boys)
children were found to have 2009 H1N1 infection during study period
(August to December 2009) (Table I). Twenty-nine (34%)
patients had significant pre-existing disorders including asthma (9),
chronic respiratory illness (6), neurological problems (4), malignancy
(2), immunodeficiency (1), disseminated tuberculosis (1), chronic liver
disease (1), chronic kidney disease (1), and restrictive cardiomyopathy
(1).
TABLE I
Demographic Profile of Children With 2009 H1N1 Influenza (N=85)
Characteristics |
Number (%) |
Males |
55 (64.7) |
Age (mean) |
7.5 ± 3.5 years |
≤ 2 years |
06 |
2-5 years |
25 |
5- 9 years |
25 |
9-16 years |
29 |
History of contact |
22 (26) |
History of foreign travel |
2 (3) |
After fever, cough and coryza were the most common
symptoms. Other symptoms included sore-throat, vomiting, headache,
diarrhea, respiratory distress, myalgia, lethargy, decreased oral
acceptance, hypotension, wheezing, croup, flushed face. Mean (± SD)
duration of symptoms was 3.9 (± 2) days and median duration was 5 days
(range, 1-15).
Antiviral therapy (oseltamivir) was initiated in 76
(89%) patients at a mean of 5.3 ± 1.8 days after the onset of illness.
Fifty two patients (68%) started showing response to oseltamivir (in form
of being afebrile and improved subjective wellbeing) within 24 hours. Out
of 85 children, 9 recovered without administration of oseltamivir or
antibiotic. In 44 (51.8%) children, antibiotics were started either due to
severe upper respiratory or chest symptoms or possible infection/sepsis.
Twenty six children received oseltamivir alone for recovery.
Thirty (35.3%) children required hospitalization for
various reasons. Among 20 children having respiratory distress, 17
children were hypoxic at admission and required oxygen therapy. Of these
17 children, 6 children required mechanical ventilation as well as
vasoactive medication support for shock. Mean length of hospitalization
was 131±76 hours.
Three children developed ARDS and succumbed to the
illness, all other children recovered. Of the 3 children who died, one (12
years old) had underlying steroid resistant nephrotic syndrome with
chronic kidney disease and he was admitted with diagnosis of severe
pneumonia and tested positive for H1N1 influenza infection; the child died
within 24 hours of admission. Another (age 9 years) had diagnosis of
refractory epilepsy with developmental delay and he was admitted with
severe pneumonia. The third child (2.5 years) who died had diagnosis of
tuberous sclerosis with Lennoux-Gastaut syndrome and presented with ARDS
with refractory shock and died of refractory hypoxemia.
Mean (SD) total leukocyte count was 7915 (3908)/mm3
and mild leucopenia (<5000/mm3) was observed in 35% children (includes 2
children with febrile neutropenia). Mean (SD) hemoglobin level (n =
41) was 10.9 (1.3) g/dL with low level (<10 g/dL) observed in 8 children.
Mean (SD) platelet count (n=41) was 2.01 (1.09) lakh/mm3 with thrombocytopenia (platelets <150000/mm3) being observed in 37.5% children
(15/41). Four children (out of 30) had elevated total serum bilirubin
(>1mg/dL) and among these 2 had underlying chronic liver disease. Fourteen
children (out of 30) had elevated ALT and AST, with 10 children having
elevation of both ALT and AST >2 times upper normal limit (0- 40 IU/L).
Abnormalities in chest radiography were detected in 18 (out of 34)
children on presentation/admission or during hospitalization. The most
common features were infiltrates either unilateral or bilateral (41.2%)
followed by consolidation patch involving one or both lung fields (11.8%).
Few bacterial co-infections were detected as bacterial
diagnostic tests were not performed in all patients; blood samples for
cultures were taken only in hospitalized children. Only one of the
hospitalized children had blood culture positive sepsis (Klebsiella
pneumoniae).
The risk factors for hospitalization are shown in
Table II. The mean age of children who required hospitalization
was lower than those who received ambulatory care. The risk factors for
hospitalization were: children with underlying co-morbid condition, and
children with symptoms like-respiratory distress, vomiting, wheezing, or
diarrhea. Children having infiltrates/consolidation patch on chest
radio-graph were also more prone for hospitalization. Children who were
hospitalized had a longer duration of symptoms and also a longer interval
between onset of symptoms and initiation of oseltamivir.
TABLE II
Risk Factors for Hospitalization in the Study Population
Characteristics |
Group A |
Group B |
P |
|
n = 55 |
n = 30 |
value |
Age (y) (mean ± SD) |
8.2 ± 3.3 |
6.4 ± 3.8 |
0.018 |
Sex; male (%) |
31 (56.4) |
24 (80) |
0.029 |
Underlying co-morbid condition (%) |
8 (14.5) |
21 (70) |
<0.001 |
Symptoms (%) |
Respiratory distress |
0 |
20 (66.7) |
<0.001 |
Vomiting |
9 |
8 (26.7) |
<0.001 |
Wheezing |
1 |
7 (23.3) |
0.002 |
Diarrhea |
0 |
3 (10) |
0.04 |
Duration of symptoms at presentation (d) (mean ± SD) |
3.5 ± 1.3 |
4.7 ± 2.6 |
0.03 |
Interval between onset of symptoms and initiation of oseltamivir (d)
(mean ± SD) |
4.8 ± 1.3 |
6.1 ± 2.1 |
0.007 |
Infiltrates/consolidation on chest radiograph (%) |
1/13 (7.7) |
17/21 (80.9) |
<0.001 |
Antibiotic treatment (%) |
24 (43.6) |
20 (66.7) |
0.042 |
SD = standard deviation; Group A received ambulatory treatment; Group B received hospitalization.
Number in parentheses are
|
Discussion
As of 10 January 2010, worldwide more than 208
countries and overseas territories or communities have reported laboratory
confirmed cases of pandemic influenza (H1N1) 2009, including at least
13554 deaths [11]. But in the Indian
subcontinent, there are more than 23727 laboratory confirmed cases with
more than 782 (3.3%) deaths [6]. Our experience of the pediatric 2009 H1N1
influenza infection in New Delhi, India, shows that presentations can be
atypical, severity is associated with underlying disease, and rates of
secondary bacterial infection are low.
The proportion of children who had an underlying
condition in our study (38%) was similar to that reported in children with
seasonal influenza (31-43%) [12-14].
As in patients with seasonal influenza, asthma was the most common
underlying conditions in our patients [12]. Antiviral drugs were
administered to most patients (89.4%), but such therapy was started more
than 48 hours after the onset of illness in a majority of the patients.
The interval between the onset of symptoms and the initiation of
oseltamivir was longer in children who were hospitalized than those who
received ambulatory care. This is similar to that reported in other series
[15,16]. Due to non-specific symptomatology children who had not received
oseltamivir timely had high probability of hospitalization, thus adding to
the impression of delayed administration of oseltamivir in hospitalized
children. Secondly, being a tertiary care hospital, children referred from
outside with severe illness (without obvious cause) were tested only after
getting admitted to our hospital; there was a time gap for administration
of oseltamivir after onset of illness.
While the risk factors/groups are not well defined for
the 2009 H1N1 influenza, they are likely to be similar to those for
seasonal influenza. Patients susceptible to severe disease are – those
younger than five years and over sixty five years of age, pregnant women,
those with systemic illnesses, adolescents on aspirin, residents of
nursing homes and immune suppressed. Among these, children younger than 4
years have the highest complication and death rates [16].
Pediatric data for severe disease include: chronic respiratory illness
including asthma, neuromuscular disorders, cerebral palsy, developmental
delay, immunodeficiency, heart disease, and prematurity [7,9,16].
Majority of children with underlying disease fully
recovered, which may be explained by seeking medical attention before
serious complications as many were children of parents who are employed in
our hospital, this group also includes children in follow up clinics for
major illnesses. Hospitalized children were more likely to receive
antibiotics in view of possible sepsis/infection or complications.
Patients who expired came to hospital in an advanced stage of illness. Out
of three deaths, two occurred in children who presented with serious
complication of acute lung injury and one had profound shock at
presentation. All expired within 24 hours of hospitalization.
We found history of contact in only 26% children; this
suggests that H1N1 flu was widespread in the community. Travel history was
also not significant now as only two children had history of foreign
travel. Clinical features and routine laboratory investigations were
non-specific and also could not be distinguished from other viral
infections, as described previously. The clinical features of patients who
were hospitalized with 2009 H1N1 influenza were generally similar to those
reported during peak periods of seasonal influenza and past pandemics with
an acute onset of respiratory illness [17-20]. Whereas diarrhea or
vomiting have occasionally been reported in children during peak periods
of seasonal influenza [18], these symptoms were reported in 10-27% of
patients in our study. Incidence of diarrhea was reported to be between
8-20% and vomiting in 10-40% in children infected with swine origin H1N1
infection [9,16]. In one report incidence of diarrhea or vomiting was
reported to be in 42% of children [15]. As found in other studies,
occasional case may present without respiratory symptoms. Recovery was
very fast in all the patients irrespective of underlying illness, which is
in contrast to other studies. Some patients recovered without
complications even without antiviral therapy, so antiviral therapy may not
be required in all cases. Few complications in the patients including
those with underlying high risk illness tells that majority of children
will have a benign course.
Our study has several limitations. In this
retrospective chart review, majority of the patients we evaluated were
children of hospital employees, who may seek early evaluation and
treatment. The number of children evaluated was also small (though it is
the largest data on pediatric H1N1 flu from a single centre). We evaluated
only patients with confirmed 2009 H1N1 influenza virus infection, so the
group may not be representative of patients who may not have been tested.
Finally, despite the use of a standardized data-collection form, not all
information could be collected for all patients.
Clinicians should consider H1N1 influenza in the
differential diagnosis of children with pre-existing disorders who present
acutely to health services even if there are no classic flu like symptoms
or an alternative diagnosis is suspected, especially if there are severe
symptoms or underlying disease. It is imperative that further data are
collected prospectively on the clinical presentations and predictors of
severity in H1N1 influenza.
To conclude, H1N1 infection should be considered in the
differential diagnosis for patients presenting with fever and respiratory
illness or pneumonia. Majority will have a benign course. As the 2009 H1N1
pandemic evolves, continued investigation is needed to better define the
clinical spectrum of disease and risk factors for an increased severity of
illness, which will allow for improvements in treatment guidance.
Acknowledgments: We acknowledge the help provided
by CDC, Atlanta (USA), National Institute of Virology, Pune, and Indian
Council of Medical Research (ICMR), New Delhi, in training of laboratory
personnel for RT PCR and reagents.
Contributors: RRD, AS, RL, RJ, RS and SKK:
collected data. SK, BBS, MA and SB performed laboratory tests. RRD, RL and
SKK analyzed data and wrote the manuscript. All authors reviewed and
decided to submit the manuscript for publication.
Funding: Training for RT PCR and reagents
were provided by CDC, Atlanta (USA); National Institute of
Virology, Pune, India; and Indian Council of Medical Research, New Delhi,
India.
Competing interest: None stated.
What Is Already Known?
• The clinical features of the ongoing
Swine origin influenza pandemic are non-specific and are similar to
other viral infections.
What This Study Adds?
• Clinical features and routine laboratory
investigations in children with swine origin influenza were
non-specific.
• Risk factors for hospitalization include:
underlying co-morbid condition, respiratory distress, vomiting,
wheezing, diarrhea, or hypotension, infiltrates/consolidation on
chest radiograph.
• Majority of the children with swine origin
influenza had a benign course and a good outcome.
|
References
1. Chang LY, Shih SR, Shao PL, Huang DT, Huang LM.
Novel swine-origin influenza virus A (H1N1): the first pandemic of the
21st century. J Formos Med Assoc. 2009; 108: 526-32.
2. Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S,
Garten RJ, et al. Emergence of a novel swine-origin influenza A
(H1N1) virus in humans. N Engl J Med. 2009; 360:2605-15. [Erratum, N Engl
J Med. 2009; 361: 102.]
3. 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.
4. Morens DM, Taubenberger JK, Fauci AS. The persistent
legacy of the 1918 influenza virus. NEJM.2009;361: 225 -9.
5. Clinical management of human infection with new
influenza A (H1N1) virus: initial guidance. World Health Organization:
Global alert and response. 21 May 2009. Available from: http://www.who.int/csr/resources/publications/swineflu/clinical_management/en/index.html.
Accessed on 15 February, 2010.
6. Epidemiological Trends of Pandemic Influenza A
(H1N1). Ministry of Health and Family Welfare, Government of India.
Available from: http://mohfw-h1n1.nic.in/Epidemiological.html. Accessed on
January 15, 2010.
7. Lister P, Reynolds F, Parslow R, Chan A, Cooper M,
Plunkett A, et al. Swine-origin influenza virus H1N1, seasonal
influenza virus, and critical illness in children. Lancet. 2009;374:605-7.
8. Surveillance for pediatric deaths associated with
2009 pandemic influenza A (H1N1) virus infection - United States,
April-August 2009. MMWR Morb Mortal Wkly Rep.2009;58:941-7.
9. Hackett S, Hill L, Patel J, Ratnaraja N, Ifeyinwa A,
Farooqi M, et al. Clinical characteristics of paediatric H1N1
admissions in Birmingham, UK. Lancet. 2009;374:605.
10. Directorate General of Health Services, Ministry of
Health and Family Welfare, Government of India. Pandemic Influenza A H1N1-
Clinical management Protocol and Infection Control Guidelines. Available
at: http://mohfw-h1n1.nic.in/documents/pdf/5.%20Clinical%20Management%20ProtocolPandemic%20influenza%20A%20H1N1.pdf. Accessed on
15 February, 2010.
11. Pandemic (H1N1) 2010 - update 83. Geneva: World
Health Organization. Available from: http://www. who.int/csr/don/2010_01_15/en/index.html.
Accessed on January 15, 2010.
12. Schrag SJ, Shay DK, Gershman K, Thomas A, Craig AS,
Schaffner W, et al. Multistate surveillance for laboratory
confirmed, influenza-associated hospitalizations in child-ren: 2003-2004.
Pediatr Infect Dis J. 2006; 25:395-400.
13. Keren R, Zaoutis TE, Bridges CB, Herrera G, Watson
BM, Wheeler AB, et al. Neurological and neuromuscular disease as a
risk factor for respiratory failure in children hospitalized with
influenza infection. JAMA.2005;294: 2188-94.
14. Ampofo K, Gesteland PH, Bender J, Mills M, Daly J,
Samore M, et al. Epidemiology, complications, and cost of
hospitalization in children with laboratory - confirmed influenza
infection. Pediatrics 2006; 118: 2409 - 2417.
15. Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit
SR, Louie J, et al. Hospitalized patients with 2009 H1N1 influenza
in the United States, April–June 2009. N Engl J Med.2009;361:1935-44.
16. Libster R, Bugna J, Coviello S, Hijano DR,
Dunaiewsky M, Reynoso N, et al. Pediatric hospitalizations
associated with 2009 pandemic influenza A (H1N1) in Argentina. N Engl J
Med.2010;362:45-55.
17. Nicholson KG. Clinical features of influenza. Semin
Respir Infect.1992;7:26-37.
18. Cox NJ, Subbarao K. Influenza.
Lancet.1999;354:1277-82.
19. Moore DL, Vaudry W, Scheifele DW, Halperin SA, Dery
P, Ford-Jones E, et al. Surveillance for influenza admissions among
children hospitalized in Canadian immunization monitoring program active
centers, 2003-2004. Pediatrics.2006;118: e610-19.
20. Louria DB, Blumenfield HL, Ellis JT, Kilbourne ED,
Rogers DE. Studies on influenza in the pandemic of 1957-1958. II.
Pulmonary complications of influenza. J Clin Invest.1959;38:213-65.
|
|
|
|