Viral Infections in the oncology patient
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Shared care information
Children under the care of oncology units vary in their degree of immunosuppression. Some children will have near normal immunity and responses to common viral infections while others will have severe immuno-compromise. All patients presenting with a viral infection should be discussed with the paediatric oncologist on call. This can be via the oncology unit the next day for well children or urgently if they are unwell or have an oxygen requirement. Children who are exposed to measles or varicella should have prophylaxis if they meet the criteria listed.
CMV infection in oncology patients may be primary infection or reactivation of latent CMV. It is most commonly seen after allogeneic stem cell transplantation but can also occur in other patients especially those on lymphosuppressive therapy such as ALL.
- Hepatosplenomegaly/abnormal LFTs
- Atypical mononuclear cells on blood film
- Retinitis (rare)
- Pneumonitis (rare except after HSCT)
- PCR for CMV from urine and serum
- nasopharyngeal aspirate or BAL for PCR.
- Ganciclovir 5 mg/kg/dose IV bd. Use may be limited by myelosuppresssion.
- Foscarnet 90 mg/kg/dose bd
- Cidofovir(2) (second line therapy for treatment failure) 5 mg/kg/week for 2 weeks then 5 mg/2 weeks
- Immune globulin. Use is controversial as several studies have suggested that IVIg does not improve outcome.
- Valgancyclovir as maintenance therapy.
Herpes Simplex Virus
Shared care information
HSV infections can disseminate in oncology patients. Patients with uncomplicated "cold sores" can be treated with PO acyclovir but all patients should be discussed with the paediatric oncologist on call during working hours. More significant infections should be admitted for IV acyclovir.
Children may present with discrete "cold sores" or with more generalised oral ulceration (especially when associated with mucositis). This can progress to herpes oesophagitis. Dissemination can occur to the CNS (herpes encephalitis) or occasionally to the respiratory system.
Diagnosis is with viral PCR and culture on tissue fluid or swabs, usually with a background of previous known HSV IgG positivity.
Patients on therapy or for 3-6 months after completion of treatment who present with HSV should be treated with:
- Discrete "cold sores" in patients who are thought to be at low risk of dissemination may be treated with acyclovir 200mg (< 2yrs) or 400mg (>2 years) PO 5 x/day.
- Valacyclovir is available which has a BD dosing schedule but is more expensive and use should be decided by the treating paediatric oncologist on a case by case basis.
This is used for patients undergoing stem cell transplant who have had previous cold sores and are known to be HSV positive at diagnosis:
- 250mg/m2/dose q8h until N >1.0 then acyclovir 200mg (< 2yrs) or 400mg (>2 years) PO 4 x/day until 3 months post transplant (continue if there is GVHD).
For use in patients who develop recurrent HSV infection on treatment:
- Acyclovir 200mg (< 2yrs) or 400mg (>2 years) PO 4 x/day
The incubation period for Influenza is 1 - 7 days.
Uncomplicated influenza presents with:
- nasal congestion, sore throat
- Assessments should be done in isolation cubicles to prevent viral spread.
- Nasopharyngeal aspirate for respiratory viruses (clearly labelled "Urgent - child cancer patient ?influenza").
- BAL may be required if there are lower respiratory symptoms
- CXR if diagnosis of influenza is confirmed.
Please discuss treatment and prophylactic use of oseltamivir and other neuraminidase inhibitors with Infectious Diseases.
The most common complications of influenza include pneumonitis and/or hepatitis. The National Centre for Clinical Excellence (NHS UK) recommends neuraminidase inhibitors (e.g., oseltamivir) for the prevention and treatment of influenza A and B in "at-risk" children. Immunocompromise defines patients as "at-risk" and, hence, all our patients receiving chemotherapy or haemopoietic stem cell transplantation qualify for intervention under this category.
Treatment of Influenza
Most strains of Influenza A and B respond to oseltamivir. Many of the strains in the 2008 year were resistant to oseltamivir and the recommended treatment was with combination therapy of other neuraminidase inhibitors. The current susceptibility patterns of influenza strains should be discussed with infectious disease consultant or virologist when deciding on therapy.
Safety data for Oseltamivir in <1 year is limited. Discuss use in this age group with infectious diseases regarding dosage.
During peak season Oseltamivir suspension can be in short supply. If unavailable, dissolve the 75 mg capsule in 10 mls water to give a 7.5 mg/ml solution. Discard left-over solution after dose is given.
Treatment Dose of Oseltamivir
Start therapy < 48 hours of onset of symptoms.
|Bodyweight (kg)||Dosage (suspension 7.5 mg/ml)|
|9 - 12||24 mg (3.5 mls) bd|
|12 - 15||30 mg (4.0 mls) bd|
|15 - 23||45 mg (6 mls) bd|
|23 - 40||60 mg (8 mls) bd|
|> 40||75 mg (10 mls or 1 capsule) bd|
The most effective strategy is immunisation which prevents influenza in 70% of contacts (see Immunisation Policy).
Despite immunisation, immunosuppressed patients may not seroconvert and, therefore, remain at risk of infection. Randomised controlled trials in adults have demonstrated that oseltamivir significantly reduced the risk of influenza during a community epidemic. When administered promptly for household prophylaxis (i.e., starting within 48 hours of onset of symptoms on an infected individual), 7 days treatment significantly reduced the risk of illness by 89% compared with placebo.
- has confirmed influenza, and
- has been in close contact (> 30 mins) with the "at-risk" patient
- the "at risk patient" has (a) not received the influenza vaccine or (b) has received the vaccine within 2 weeks of contact.
Treat for 7 days.
Prevention Dose of Oseltamivir
Start therapy < 48 hours of onset of symptoms in the infected contact.
|Bodyweight (kg)||Dosage (suspension 7.5 mg/ml)|
|< 15||30 mg (4.0 mls) once daily|
|15 - 23||45 mg (6 mls) once daily|
|23 - 40||60 mg (8 mls) once daily|
|> 40||75 mg (10 mls or 1 capsule) once daily|
All patients should have had measles antibodies recorded at the time of diagnosis. Patients with detectable antibodies are at minimal risk of infection unless they have had ablative therapy (stem cell transplant).
Measles is infective from 4 days before the onset of rash (1 day before the onset of prodomal symptoms) until 4 days after. If an oncology child may have been in contact with measles, rapidly establish a firm diagnosis for the contact before treating as measles.
Most immunosuppressed children with serious measles present with pneumonia or encephalitis and do not have a rash or the other typical signs of measles. Consider in patients with atypical pneumonia especially if they have not been vaccinated or if measles is currently prevalent.
- nasopharyngeal aspirate for measles PCR
- urine for measles PCR
- measles IgM (may also need a convalescent sample).
Contact Infectious Diseases (and infection control for contact tracing).
There is no effective treatment for measles pneumonia.
A randomised study has shown fewer complications in children with measles who received 200,000 IU of vitamin A (retinyl palmitate) given orally daily for 2 consecutive days after admission.
Measles encephalopathy may occur several months after the original illness. Complex and intractable seizures are usually followed by severe brain damage/death.
Following definite exposure give Normal Human Immunoglobulin (CSL 16% w/v 0.6 ml/kg by deep IM injection, maximum volume of 15 mls in 3 x 5 ml injections) as soon as possible.
Alternatively, administer IVIg 0.15 g/kg for confirmed contacts who have a central venous access or for those where large doses are required:
- This must be given regardless of the measles IgG status of the patient because measles in a patient receiving chemotherapy is often fatal.
- Preferably administer within 72 hours of exposure but give up to 6 days of exposure
- Encourage vaccination of siblings and playmates; by doing this, there is no established risk to the patient.
A known cause of pure red cell aplasia in patients with chronic haemolysis but now recognised as causing chronic anaemia (and sometimes pancytopenia) in immunosuppressed children including those with ALL in remission.
- Classical "slapped cheek" may not be present.
- There may be nonspecific viral features
- Anaemia with reticulocytopenia or occasionally pancytopenia.
- Serology IgM and IgG
- Parvovirus PCR (may be positive in patients with suppressed serological responses).
- Parvovirus can be tested on BMAT samples
High dose IV immunoglobulin.
Respiratory Syncytial Virus
Younger children often present with bronchiolitis while older
children will usual initially present with URTI symptoms.
Untreated, they may develop LRT symptoms and signs with progressive
Risk factors(7,9) for severe disease are:
- Young age ( < 2 yrs)
- Lymphopenia (not neutropenia)
- > = 2 of:
- Acute GVHD > = grade 2
- HSCT < 6 months prior
- T cell depletion < 3 months prior
- Pre engraftment
- B cell depletion < 3 months prior
Nasopharyngeal aspirate for direct immunofluorescence or PCR and culture.
- Supportive care
- Avoid fluid overload
- Nebulised ribavirin(8) (in Christchurch, contact the respiratory technician on call). Pregnant women should avoid contact with ribavirin. There is no evidence on the effectiveness of IV ribavirin.
- Standard therapy - 20 mg/ml in 300 ml administered over 18 hours via SPAG
- High dose short course (duration) - 60 mg/ml in 100 ml/day over 2 hours q8h (6 hours total).
Currently patients on high dose therapy or with 12 months of allogeneic transplant close contacts of proven RSV should be considered for IVIg prophylaxis. Special consideration should be given to those most at risk (i.e,. < 2 years with lymphopenia). Palivizumab has also been used for prophylaxis overseas.
A significant contact is defined as:
- Any close contact with an infectious child
- Infectious period is defined as 48 hours before the rash develops until crusting of all vesicles
- In immucompromised patients, VZV transmission can rarely occur after transmission from close contact with a patient with shingles. Discuss with Infectious Diseases.
Parents of at-risk patients need to be advised at the time of diagnosis about the risk and severity of chickenpox while their child is on chemotherapy. It is imperative that the school and friends are informed of the need to report outbreaks of chickenpox.
The usual incubation period for chickenpox is 10-21 days, but after ZIG the incubation period of chickenpox can be prolonged to 28 days. Appropriate isolation should be arranged for day ward or inpatient stays over this time.
- Antibody status should be available from the time of diagnosis on all patients.
- Serology varicella IgM and IgG
- PCR testing on blood or lesional fluid.
Treatment of primary infection
For possible or proven chicken pox:
- Aciclovir IV for 5 days and then PO if responding.
- For shingles (reactivation VZV):
Treat severe infection as for primary chicken pox. Less severe infection may be treated with oral medication alone
Who needs preventive treatment after exposure?
VZV IgG -ve patients:
- Until 3 months after completing chemotherapy
- Patients who have received ATG/Campath or other T cell immunomodulation or Fludarabine previously should be discussed with the paediatric oncologist.
Regardless of VZV IgG status:
- all children on chemotherapy (note this differs from the current NZBS guidelines)
- 12 months after allogeneic stem cell transplantation. (May be longer if chronic GVHD present.)
- 6 months after autologous stem cell transplant.
Prophylactic Treatment after Exposure
Please see section on Page 2 of the document "Immunisation of children during and after cancer therapy". Note that while this refers to children on maintenance therapy for ALL this guide should be used for all children currently receiving chemotherapy or recent immunosuppressive therapy for conditions such as Aplastic anaemia. If there are any queries as to whether a patient should receive treatment please discuss with the paediatric oncologist on call at your local centre.
Primary prevention (vaccination)
Chickenpox Vaccination for siblings and close contacts
Vaccination of siblings and close contacts of the patient to 'ring fence' the immunocompromised individual should be encouraged.
Healthy children receiving the varicella vaccine are unlikely to transmit the virus. Some children developed vesicles between day 5 - 26 following vaccination.
Recommendations from the Center for Disease Control (USA) states that "if a susceptible, immunocompromised person is inadvertently exposed to a person who has a vaccine-related rash, VZIG need not be administered because disease associated with this type of transmission is expected to be mild". But if the vacinee develops a rash, we advise isolation of the immunocompromised child from the vacinee until lesions are crusted.
Acute lymphoblastic leukaemia patients can now be vaccinated with a LOW TITRE live varicella vaccine during continuation chemotherapy. This should be discussed with the paediatric oncologist and ID physician.
- Boeckh M, Lgungman P. How I treat Cytomegalovirus in haematopoetic cell transplant recipients. Blood 2009;113(23):5711-5719
- Steininger C. Novel therapies for cytomegalovirus disease. Recent patents on antiinfective drug discovery.2007;2:53-72.
- Caspar C, Englund J, Boeckh M. How I treat influenza in patients with haematological malignancies. Blood 2010;115(7):1331-1341.
- Hussey GD, Klein M. A randomized controlled trial of vitamin A in children with severe measles. NEJM 323:160-164,1990.
- Ministry of Health document: Active and Passive Prophylaxis for contacts of measles
- Florea AV, Ionescu DN, Melhem MF. Parvovirus B19 infection in the immunocompromised host. Arch Pathol Lab Med;2007;131:799-804.
- El Saleeby CM et al. Risk factors for severe respiratory syncytial virus disease in children with cancer: the importance of lymphopenia and young age. Ped 2008;121(2):235-243
- Englund et al. High-dose, short-duration ribavirin aerosol therapy compared with standard ribavirin therapy in children with suspected respiratory syncytial virus infection. J Ped; 1994;125(4):635-641
- Kanna N et al. Respiratory Syncytial Virus infection in patients with haematological diseases:single centre study and review of the literature. CID 2008:46:402-412.
- Chavez-Bueno S et al.Intravenous Palivizumab and ribavirin combination for Respiratory syncytial virus disease in high risk pediatric patients.Paediat Inf Dis J;2007;26:1089-1093.
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- Date last published: 03 March 2014
- Document type: Clinical Guideline
- Services responsible: National Child Cancer Network
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