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This guidelines provides information for the use of anti-virals in children who have received a human stem cell transplant.
This guideline has been developed to be used for children with haemato-oncology conditions.
Viral infection in the immunocompromised patient can be life threatening despite the use of prophylaxis. Patients thought to be infected should be assessed rapidly and treatment initiated promptly. It must be remembered that immunocompromised patients can present atypically without pyrexia and without any localising features indicating the source of the infection. The possibility of infection with opportunistic organisms such as PCP and reactivation of previous infections e.g. CMV, VZV should always be considered. Viruses such as those responsible for the common cold can cause pneumonitis and death in recipients of allogeneic stem cell transplants. Small children may be particularly vulnerable to viral infection because of lack of previous exposure. Adenovirus is amongst the commonest causes of Haemopoietic Stem Cell Transplant (HSCT) procedure related mortality in children.
Viruses can cause many different symptoms and should always form part of a differential diagnosis for any immunocompromised patient. The viruses listed below are examples of the commonest identified in HSCT patients. For other viral infections see related documentation.
|LRTI (pneumonia)||CRV, CMV, Adenovirus|
|Oesophagitis/Gastritis/Colitis||HSV, CMV, Adenovirus|
|Diarrhoea||Rotavirus, Adenovirus, Norovirus, Sapovirus, Astrovirus, CMV|
|Haemorrhagic Cystitis||Polyomavirus, Adenovirus|
|Hepatitis||HAV, HBV, HCV, CMV, EBV, Adeno (HSV, VZV, HHV6, Enteroviruses)|
|PUO||CMV, EBV, Adenovirus, HHV6|
|Meningitis||HSV, VZV, Enteroviruses|
|Encephalitis||HSV, CMV, EBV, HHV6, VZV|
See 'related guidelines' section at the bottom of this guideline
3.1 The diagnosis and management of viral disease will be directed by the Consultant/Associate Specialist or a senior member of the medical team.
3.2 The Medical/nursing team will be responsible for the monitoring & investigation of viruses. Microbiology/Virology staff will inform of recent virology results as they become positive.
4.1 IV/Oral Drug Kardex
4.2 IV Fluid Prescription Chart
For further information including clinical features see Pulmonary Complications Pre & Post HSCT SOP (YBMT-CLIN-0016)
At Risk Group
Patients with respiratory symptoms or signs within any of the listed risk groups should be discussed with the HSCT Consultant or HSCT Associate Specialist. The decision to start treatment will be based on the patient’s clinical condition, previous treatment etc:
This list is not exhaustive and other patients can develop pneumonitis although this is less common. It should be remembered that the presence of a virus may not be the cause of the patient’s symptoms.
RSV has a 15-20% mortality from pneumonitis in the allograft population. Patients who are RSV positive pre-allogeneic transplant should not begin conditioning until symptoms have settled and viral shedding ceased.
Pre HSCT assessment, which includes nasopharyngeal aspirate (NPA) and throat swab for respiratory viruses.
Refer to Respiratory Syncytial Virus (RSV) NHSGG&C Control of Infection Committee Policy www.nhsggc.org.uk/infectioncontrol
If an allograft patient is in the same room as a known case, the patient must be screened.
Ribavirin IV Dosing is not recommended for treatment of infants with RSV - SIGN guidelines 2006
|33mg/kg||Loading dose, then|
|16mg/kg||6hrly for 4 days, then|
|8mg/kg||8hrly for 3 days, then review|
Parainfluenza 3 has mortality from pneumonitis of about 5-10% in the allograft population.
Patients who are positive pre-allogeneic transplant should not begin conditioning until symptoms have settled and viral shedding ceased.
LRTI should be discussed with HSCT consultant or HSCT associate specialist. IV Ribavirin is a treatment option which may be used (see above dosing table) for a maximum of 10 days, however there is little evidence to support its efficacy.
Flu A has a higher mortality than flu B from pneumonitis.
If a patient on the HSCT Unit or a patient attending as an outpatient is Flu A/B positive consider giving HSCT patients who have been in prolonged contact prophylactic treatment. Current recommendations are that severely immunocompromised patients should receive Zanamivir as first line therapy, with Oseltamivir as second line therapy where Zanamivir is not a suitable option (see below for details).
Treatment for Influenza A and B and H1N1
Influenza A and B
NB: This MUST be initiated by the HSCT Consultant/Associate Specialist.
Severely immunocompromised patients should receive inhaled Zanamivir as first line therapy.
Inhalation of powder
|Prevention during an epidemic of Influenza (prophylaxis)||5-18 years||10mg once daily for up to 28 days|
|Treatment of Influenza||5-18 years||10mg twice daily for 5 days|
|Post Exposure prophylaxis of Influenza||5-18 years||10mg once daily for 10 days|
Zanamivir is not licensed for children under 5 years old. For these children, and for any child unable to use the diskhaler, prescribe Oseltamivir. However, severely immunocompromised patients are at increased risk of developing oseltamivir-resistant influenza, therefore need close monitoring.
Oseltamivir may also be appropriate for any HSCT patients no longer considered to be severely immunocompromised.
Oseltamivir (Tamiflu) Dosing: (give once daily for 10 days for prophylaxis and twice daily for 5 days for treatment):
|3mo - 1 year||3mg/kg|
*Follow up testing may also be indicated in outbreak situations. During an epidemic prophylaxis may be used up to 6 weeks.
NB: For severely immunocompromised patients who are unable to receive Zanamivir via diskhaler and/or in cases of suspected or confirmed oseltamivir resistance, an aqueous solution of Zanamivir is available for nebulisation or IV administration. This is an unlicensed preparation which is only available on a named patient basis direct from GSK. Contact details are available in HPS Guidance document (2013)
Severely immunocompromised patients should receive inhaled Zanamivir as first line therapy (see 5.1.3).
If the patient is not considered severely immunocomprimised treat initially with Oseltamivir (see 5.1.3). If no response to treatment with Oseltamivir consider the possibility of drug resistance. Zamanivir is an alternative viral neuraminidase inhibitor, which may be used following discussion with the virologist.
Post exposure PROPHYLAXIS: as per dosing guidelines in 5.1.3 at using prophylactic regimen.
This is a recognised cause of idiopathic pneumonia in immunocompromised children, putting them at risk of severe disease and hospitalisation. Patients develop rapidly spreading infiltrates and hypoxia. There are no large published studies to guide treatment. IVIgG has been used and Ribavirin demonstrates some in vitro activity.
HHV6 is a ß herpes virus with similarities to CMV and HHV7. It is widespread in the human population, and persists in the lymphocytes and salivary glands. It can be reactivated during times of immunosuppression.
NB: This MUST be initiated by the HSCT Consultant/Associate Specialist
Duration: Until patient improves
100-200mg four times daily orally
200-400mg four times daily orally
At Risk Group
Pre HSCT assessment, which includes serological testing
1st line: ACICLOVIR IV
Child 1 - 3 months
20mg/kg three times daily for 14 days (21 days if CNS involvement)
500mg/m2 three times daily for 5 days (21 days if CNS involvement)
10mg/kg three times daily for 5 days (21 days if CNS involvement)
NB: Commence IV maintenance fluids during IV aciclovir administration. In renal impairment see dose adjustment table (Section 5.3).
If aciclovir resistance is suspected, a swab in viral transport medium
should be sent to virology.
2nd line GANCICLOVIR see dosing and administration in Diagnosis & Management of CMV SOP (YBMT-CLIN-0014)
3rd line: FOSCARNET IV infusion 40mg/kg three times a day for 2 - 3 weeks or until lesions heal (see dosing & administration).
NB: VZV titres should be assessed for of all at risk patients prior to commencement of immunosuppressive treatment. See Chickenpox & Measles in the HSCT Setting SOP (YBMT-CLIN-0018)
|Aciclovir||Oral prophylaxis:||Estimated GFR 10-20||HSV: normal dose 3-4 times/day
VZV: normal dose 8 hourly
|Estimated GFR < 10ml/min give normal dose every 12 hours|
|IV therapy:||Estimated GFR 25-50ml/min give normal dose every 12 hours
Estimated GFR 10-25ml/min give normal dose every 24 hours
Estimated GFR <10 ml/min give 50% dose every 24 hours
|Oseltamivir||Reduce dose if:||Estimated GFR <30 ml/min give 50% dose
Estimated GFR <10 ml/min - not recommended
|Ganciclovir||See Diagnosis and Management of CMV SOP|
|Foscarnet||See Diagnosis and Management of CMV SOP|
Last reviewed: 01 March 2015
Next review: 01 March 2017
Author(s): Dr A M Ewins
Approved By: Clinical Effectiveness