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Case Report

Indian Pediatr 2011;48: 971-973

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.

 

 

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.


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,
  cytosine arabinoside methotrexate D+31 daunorubicin and L-asparaginase
  (3+7 regimen)    
WBC/ANC (X109/L) 8.5/0.6 0.2/0 1.7/1.0
Clinical features
 
high grade fever, dry cough, dyspnea high grade fever, dry cough
and dyspnea
dry cough and high grade fever
 
Radiological findings
(HRCT Chest)
 
bilateral multiple nodular
patchy consolidation with ground glass opacities.
 
HRCT chest not done as
radiograph was normal.

 
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
 
piperacillin-tazobactum, imipenem, vancomycin, cefoperazone-sulbactum,
amikacin, vancomycin,
amphotericin B
imipenem, amikacin, vancomycin, amphotericin B, voriconazole 
 
  amphotericin B,    
  voriconazole    
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.

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.

References

1. Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza, Bautista E, Chotpitayasunondh T, Gao Z, Harper SA, Shaw M, et al. Clinical Aspects of Pandemic 2009 Influenza A (H1N1) Virus Infection. N Engl J Med. 2010;362:1708-19.

2. Press Release from Press Information Bureau, Press Release. Government of India, May 26,2010, http://pib.nic.in/h1n1/h1n1.asp.

3. Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) – United States, May-August 2009. MMWR Morb Mortal Wkly Rep. 2009;58:1071-4.

4. Seiter K, Nadelman RB, Liu D, Ahmad T,Montecalvo MA. Novel influenza A (H1N1) in patients with hematologic malignancies. J Clin Oncol. 2010; 28: e27-e29.

5. Saurez JG, Martin Y, Callejas M, Rodriguez-Dominguez M, Galán JC, Burgaleta C, et al . Favourable outcome of pneumonia due to novel influenza A/H1N1 2009 virus in a splenectomised adult patient undergoing therapy for non Hodgkin lymphoma. Br J Haematol. 2010;148: 805-14.

6. Patel P, Sweiss K, Shatavi S, Peace D, Clark N, Rondelli D. The impact of novel influenza A (H1N1) after hematopoietic SCT. Bone Marrow Transplant. 2010; 45:1756-7.

7. Redelman-Sidi G, Sepkowitz KA,Huang CK, Park S, Stiles J, Eagan J, et al. 2009 H1N1 influenza infection in cancer patients and hematopoietic stem cell transplant recipients. J Infect. 2010;60:257-63.
 

 

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