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Indian Pediatr 2011;48: 971-973 |
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H1N1 Infection in children with Hematological
Malignancies |
Prabhat S Malik, *Shobha Broor and Sameer Bakhshi
From the Departments of Medical Oncology and
*Microbiology, Dr BRA Institute Rotary Cancer Hospital, and All India
Institute of Medical Sciences4, New Delhi 110 029, India.
Correspondence to: Dr Sameer Bakhshi, Additional
Professor of Pediatric Oncology, Department of Medical Oncology,
Dr BRA Institute Rotary Cancer Hospital, AIIMS, New Delhi 110029, India.
Email: [email protected]
Received: June 22, 2010;
Initial Review: July 14, 2010;
Accepted: August 5, 2010.
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In the recent pandemic of H1N1 infection, pediatric
patients with haematological malignancies were considered high risk
for severe illness. There is paucity of data regarding course of H1N1
infection in this subgroup. We describe H1N1 infection in 3 children
with acute leukemia. All three patients presented with neutropenic
fever; 2 had probable fungal pneumonia based on chest imaging and
galactomanan estimation. Diagnosis of H1N1 infection was delayed in
all 3 patients as it was not suspected initially. One patient died
despite treatment. H1NI infection may coexist with other infections in
febrile neutropenia.
Key words : H1N1 infection, Hematological malignancies,
Pneumonia.
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Risk factors for severe illness and death due
to H1N1 infection include young children, obesity, chronic lung
disease, pregnancy, heart disease, neurocognitive disorders and
immunosuppression [1].
In India, till now there have been 31866 confirmed cases and 1517
deaths of lab confirmed cases [2]. We describe the diagnostic
challenges, course and outcome of H1N1 infection in three children
with different hematological malignancies.
Case Report
We had three patients with different
haematological malignancies in varied phases of treatment who were
found to have H1N1 infection between December 2009 and March 2010.
The clinical details are shown in Table I. Diagnosis of H1N1
infection was based on quantitative polymerase chain reaction from
nasopharyngeal swabs. Chest radiological findings mimicked invasive
aspergillosis in two patients. Galactomanan assay was also
supporting fungal infection in these patients thereby suggesting a
diagnosis of probable invasive aspergillosis. Bronchoalveolar lavage
could be performed in only one patient (patient 3) who grew
Pseudomonas species in the lavage fluid. All children were
neutropenic at the onset of symptoms. One patient (patient 1) died
due to respiratory failure and shock. In this patient, there was a
delay of more than 10 days to initiate treatment with oseltamivir,
H1N1 infection was not suspected initially. The diagnosis and
treatment of H1N1 infection was delayed in patient 3 also, but he
improved with treatment as his disease was in remission and total
leucocyte counts and neutrophil counts were showing on improving
trend.
TABLE I Children with H1N1 Infection and Leukemia
Parameter |
Patient 1 |
Patient 2 |
Patient 3 |
Age/Sex |
17 year/male |
7 year/female |
14 year/male |
Underlying diagnosis |
AML |
Pre B ALL |
Pre B ALL |
Disease status |
active disease |
remission |
Remission |
Phase of treatment
|
day of onset of induction with daunorubicin and |
maintenance therapy with 6-mercaptopurine and |
day 27 of reinduction protocol of ALL comprising pre-dnisone,
vincristine, |
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cytosine arabinoside |
methotrexate D+31 |
daunorubicin and L-asparaginase |
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(3+7 regimen) |
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WBC/ANC (X109/L) |
8.5/0.6 |
0.2/0 |
1.7/1.0 |
Clinical features
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high grade fever, dry cough, dyspnea |
high grade fever, dry cough
and dyspnea |
dry cough and high grade fever
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Radiological findings
(HRCT Chest)
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bilateral multiple nodular
patchy consolidation with ground glass opacities.
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HRCT chest not done as
radiograph was normal.
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areas of confluent consolidation in left
upper lobe along with ground glass haziness and consolidation
in superior
segment of left lower lobe |
Galactomanan assay,
(positive OD index >0.5) |
Positive |
not done |
positive |
Treatment apart from
oseltamivir
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piperacillin-tazobactum, imipenem, vancomycin, |
cefoperazone-sulbactum,
amikacin, vancomycin,
amphotericin B |
imipenem, amikacin, vancomycin, amphotericin B, voriconazole
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amphotericin B, |
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voriconazole |
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Duration between
presentation and
diagnosis of H1N1 |
12 days |
4 days |
15 days |
Duration of oseltamivir |
2 days |
5 days |
5 days |
Dose of oseltamivir |
75 mg BD |
75 mg OD |
75 mg BD |
Response to oseltamivir |
no improvement |
improved |
no improvement |
Final outcome |
Died |
improved |
improved with continued antibiotics & antifungals |
AML – acute myeloid leukemia; ALL – acute lymphoblastic leukemia; WBC – white blood cell count;
ANC- absolute neutrophil count; HRCT – high resolution CT; OD index – optical density index.
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Discussion
It is interesting to study the course of this
infection during the recent pandemic in this subgroup of patients as
pediatric age group and malignancies both are considered to be risk
factors for severe illness due to this infection. Patients with
hematological malignancies are expected to have more morbidity and
mortality due to the already compromised immunity, associated
neutropenia, and coexistent bacterial and fungal infections. Usually
a diagnosis of bacterial infection is considered in the setting of
neutropenic fever and thereafter a fungal infection is considered if
fever persists. It is for this reason that the diagnosis of H1N1
infection was not considered initially in our patients. The
diagnosis was further delayed due to the radiological features being
suggestive of invasive fungal infection in two patients. It is
possible that H1N1 could have been a coexistent infection with other
usual infections seen in our patients rather than isolated H1N1
infection. Interestingly, bacterial co-infections have been
previously observed in lung tissues of 29% of fatal cases of H1N1
[3].
There is paucity of data on the course and
outcome of this novel infection in patients with haematological
malignancies [4-7]. Sidi, et al. [7] found in their series of
45 patients of different malignancies that H1N1 was more common in
hematological malignancies than solid tumors; however, it was not
associated with severe illness or death in any of their patients.
There is no published data so far about this infection in pediatric
patients with hematological malignancies.
In view of our findings, we suggest that in the
setting of hematological malignancies, H1N1 infection should be
considered and tested by PCR in all such children, with cough or
upper respiratory symptoms during an epidemic; whether the patient
is neutropenic or not, and even when radiology is suggestive of
classical bacterial or fungal pneumonia. Further, empiric treatment
with oseltamivir should be initiated early in these patients as this
infection appears to have an adverse outcome either due to its own
course or by having an additive effect on an underlying coexistent
pulmonary infection.
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