This document covers: 1. Chickenpox post exposure prophylaxis 2. Chickenpox treatment in immunosuppressed/on treatment patients 3. Management of immunosuppressed exposed to Measles All children with suspected malignant disease must have their immune status checked with regard to viral infections on admission as a new patient prior to any blood transfusions. The immunisation history should be documented as part of the new patient admission clerking. The agreed immune status screen for a new paediatric haematology/oncology patient is CMV IgG, HSV IgG, VZV IgG, Measles IgG and long term storage. Results from these tests must be recorded in the summary sheet at the front of the haematology/oncology notes and in the discharge summary written after the first admission. Chickenpox Incubation period: 11-20 days Contagious: 2 days prior to the onset of the rash until spots are dry, may be prolonged in immunosuppressed children Peak incidence: March May and Autumn Chickenpox is highly infectious and is transmitted by personal contact or droplet spread. Incidence is seasonal with peaks in. Vesicles appear on the face and scalp, spreading to trunk and abdomen and eventually to the limbs. Susceptible individuals can develop varicella on direct contact with open shingles: either if exposed to ophthalmic shingles, or if in contact with an immunosuppressed person with shingles in whom viral shedding is greater than in an immunocompetent individual. Risk of infection from contact with an immunocompetent person with non-exposed shingles is low. 1. Prophylaxis management of patient exposed to Chickenpox: At risk immunosuppressed patients: Varicella zoster virus (VZV) antibody negative at diagnosis being treated for malignant disease for at least 6 months after completing such treatment. Post bone marrow transplant (BMT) patients (regardless of VZV status prior to BMT) until at least 12 months after finishing all immunosuppressive treatment, or longer if the individual has developed graft versus host disease. VZV negative and high dose steroids: until at least 3 months after the treatment stopped. VZV negative and immunosuppressive drugs (e.g. methotrexate) until 6 months after treatment stopped. Page 1 of 7
Algorithm for post exposure prophylaxis management of at risk patient: VZV status of patient If antibody status not known: Can test be done and results given within seven days of exposure? If yes, wait for results and treat appropriately If not, give VZIG without testing Antibody status known and negative: Give VZIG providing it can still be given within ten days of exposure (ideally within seven days but may attenuate up to ten days) If antibody status known and positive: VZIG is not indicated 1. Confirm VZV status of Haem/Onc patient 2. Confirm diagnosis and extent of infection in index case: disseminated zoster immunocompetent individual with exposed lesions immunosuppressed individual with localised zoster on any part of the body 3. Assess whether exposure is significant, the following are classed as significant contact if they have occurred between 48 hours before onset of a chickenpox rash and crusting of all lesions: a. in the same room (e.g. house, classroom or 2-4 bedded hospital bay for 15 minutes or more) or b. face-to-face i.e. playing together etc (kissing contact) 4. Decide whether patient requires treatment 5. If the patient meets the requirements for VZIG, this will be prescribed by the microbiology team. In all such cases contact the virology Consultant or the microbiology SpR to discuss the case and arrange urgent VZV antibody testing. 6. Inform Paediatric infectious diseases team. Page 2 of 7
Varicella Zoster Immune Globulin (VZIG) VZIG Doses (as per CBNF) via deep intramuscular injection using a 21G needle as the preparation is viscous. Because of the relatively large volume, consider giving half the volume in each leg. In patients with clotting disorders VZIG can be given subcutaneous. Neonate - 6 years 250mg 6-11 years 500mg 11-15 years 750mg 15-18 years 1000mg About half of susceptible immunosuppressed home contacts will develop clinical chickenpox despite VZIG prophylaxis, and a further 15% will be infected sub-clinically (Evans et al., 1980). Severe or fatal varicella can occur despite VZIG prophylaxis. Immunocompromised contacts given VZIG should therefore be monitored and aciclovir should be used at the first signs of illness. If a second contact occurs after 3 weeks, VZV antibody testing should be repeated. A second dose of Varicella Zoster Immune Globulin (VZIG) is required if the patient remains seronegative. NB: the administration of VZIG does not lead to serum antibody levels detectable by routine laboratory tests. Alternatives to VZIG: Aciclovir is another alternative to VZIG and is given orally at a prophylactic dose of 10mg/kg 6 hourly for 7 days starting 1 week after exposure. Valaciclovir 20mg/kg bd orally discuss with Dr Pollard or Dr Jeffrey. Intravenous immunoglobulin infusion dose: 0.4g/kg. Follow drug monograph for administration details. This should be used in patients with bleeding disorders/on anticoagulant therapy where deep IM injections may be problematic. Whichever method of prophylaxis is used the patient and family should be instructed to contact the specialist unit immediately if any suspicious skin lesions develop so that early treatment with intravenous aciclovir may be considered. Page 3 of 7
2. Management of patient with suspected Chickenpox First line treatment for chickenpox is inpatient intravenous aciclovir IV aciclovir dose (confirm doses in latest edition of CBNF): Neonate - 3 months 10mg/kg 8 hourly for at least 7 days. 3 months - 12 years 500mg/m 2 8 hourly usually for 5 days. Over 12 years 10mg/kg 8 hourly usually for 5 days. Discuss all patients with suspected chickenpox infection with a senior staff member. If the diagnosis is in doubt, admit and initiate treatment (which can be terminated if chickenpox subsequently becomes unlikely). Confirm suspected chickenpox infection in an immunosuppressed child take a swab from the base of a vesicular lesion (i.e. to include both vesicular fluid and cells from the base of the vesicle), place in virus transport medium, and send to the laboratory for VZV PCR. Caution: aciclovir is nephrotoxic: In obese patients, calculate on the basis of ideal weight for height. Maintain adequate hydration Monitor daily U&E, creatinine (may see a decline in renal function necessitating a dose adjustment). Give IV fluids for at least the first 24 hours. Usually treat for 10 days (usually at least 7 days being IV treatment) Dosing changes (as per CBNF): o Creatinine clearance 25-50 ml/min/1.73m 2 give dose 12 hourly o Creatinine clearance 10-25 ml/min/1.73m 2 give dose 24 hourly. In well patients, treatment may be completed at home on oral treatment only after discussion with a senior member of staff: Oral aciclovir treatment dose (CBNF): o 1 month - 12 years 20mg/kg (max 800mg) 4 times daily. o 12 18 years 800mg 5 times daily. Oral valaciclovir treatment (CBNF) o Patients within 6 months of completing chemotherapy and not considered very high risk, or who develop chickenpox post VZIG may be treated with oral valaciclovir on recommendation by Dr Jeffery or Prof Pollard only. (Dose 20mg/kg tds for 7-10 days or for children 12-18 years 1g tds for 7-10 days.) Page 4 of 7
Shingles (Herpes Zoster) Shingles is caused by a reactivation of the patient s varicella virus. Immunocompromised patients who develop shingles can usually treated on an outpatient basis with oral aciclovir (doses as for chickenpox) and chemotherapy may be continued provided the patient is kept under regular review. Treatment should be initiated within 72 hours of the onset of the rash, and continued for 7-10 days. If the patient is particularly high risk, if lesions do not heal or the condition progresses, consider stopping chemotherapy and treating with IV aciclovir. Shingles Prophylaxis: primary/secondary Post BMT/autologous rescue patients are treated with acyclovir to prevent recurrence of VZV or HSV (herpes simplex virus). Patients who have experienced recurrent or persistent chickenpox in treatment. Varicella Vaccine Recommendations The Varicella Vaccine is not routinely recommended for use in children with malignancies, but may be used on a compassionate basis in children with leukaemia. 85% of children with ALL during maintenance therapy have serologic evidence of an immune response after receiving one dose, and more that 90% after two doses, independent of whether chemotherapy is withheld or not. Immunocompromised children have a higher incidence of vaccine associated varicella than healthy children (up to 40% versus <5%); however, the vaccine associated illness usually has an extremely mild, often sub clinical course. Also, the vaccine provides a protective effect against zoster and, with a booster, reduces the risk from 15% to 3%. If a decision is taken to administer: It should be administered to susceptible children with ALL during maintenance, 12 months after documented remission. Give 2 doses (first confers immunity, second dose given 3 months later boosts the antibody titre). Check antibody titre at least 8 weeks later. How to give the vaccine Chemotherapy should be interrupted for 1 week before and 1 week after the patient receives the vaccine i.e. in a 4 week cycle of vincristine and dexamethasone, stop oral 6-Mercaptopurine and methotrexate 1 week after vincristine and dexamethasone. (It is not necessary to interrupt therapy for the second injection). Page 5 of 7
A full blood count should be checked at the time of vaccination, and the absolute lymphocyte count should be at least 0.7 x 10 9 /l. OUH uses Varilrix vaccine, given subcutaneous, preferably into the deltoid region. Vaccinated children should be kept in isolation from other immunocompromised children for 4-5 weeks after the vaccine due to the possibility of vaccine associated varicella. Cases of varicella zoster are reported after immunisation these maybe treated with aciclovir given intravenously if clinically severe. Attempts should be made to culture the virus and establish whether it is vaccine or wild type. NB it is highly recommended that siblings and carers who have not had chickenpox and are VZV negative be offered vaccination via the GP. 3. Management of immunosuppressed exposed to measles Measles Incubation period: Approximately 10 days (7 18 days) Contagious: onset of prodromal symptoms until four days after the appearance of the rash. Peak incidence: Autumn Diagnostic investigation: IgM in the saliva between 3 days - 6 weeks after the onset of the rash or parotid swelling Measles can be fatal in immunocompromised children, usually as a result of encephalitis or pneumonia. The following children fall into this group: Still receiving chemotherapy Post BMT (bone marrow transplant) patients until at least 12 months after finishing all immunosuppressive treatment or longer if the individual has developed graft versus host disease. All patients receiving high dose steroids until at least 3 months after the treatment has stopped. Patients receiving other types of immunosuppressive drugs (e.g. methotrexate) until 6 months after treatment Page 6 of 7
Regardless of antibody status (neither previous vaccination nor a low level of antibody will guarantee protection in the profoundly immunosuppressed). 1. Confirm diagnosis in index case: Clinically diagnosed or virologically confirmed disease if possible (do not wait confirmation if delay expected). 2. Significant contact would be: a. play or direct contact for 15 minutes with index case. b. contact during the infectious period i.e. between 5 day prior to until 4 day after the onset of the rash. 3. Passive immunisation with Human Immunoglobulin: As soon as possible if within 14 days of contact (ideally within 6 days but most effective if within 72 hours). Use Human Normal Immunoglobulin administered intramuscularly in the upper outer quadrant of the buttock or anterolateral thigh. If more than 3ml is to be given to a young child, or more than 5ml to older child, the immunoglobulin should be divided into smaller amounts and given in different sites. Dose: under 1 year 250mg 1 3 years 500mg over 3 years 750mg Alternatively if thrombocytopenia give intravenous immunoglobulin infusion. The dose is 0.4g/kg. Follow drug monograph for administration details. This will provide approximately four weeks protection. NB there is no specific drug treatment for measles nurse in isolation off the oncology unit. Review Name Revision Date Version Review date Dr Sheila Lane, New doc June 2010 1.0 June 2012 Paed Oncology Consultant Dr Shaun Wilson, Paed Oncology Consultant Format change Significant process update Sept 2015 Sept 2017 Page 7 of 7