Update: Intravenous immune globulin in childrendownloads.hindawi.com/journals/cjidmm/1995/198693.pdf · mu no de fi ciency vi rus (HIV) in fec tion dem on strated that pro - phy lac

Update: Intravenous immuneglobulin in children

T HE INFEC TIOUS DIS EASES AND IMMU NI ZA TION COM MIT TEE OF

the Ca na dian Pae di at ric So ci ety made rec om men da -tions on the use of in tra ve nous im mune globu lin (IgIV) in chil -dren in 1992 (1). Cer tain con di tions were listed in which theef fi cacy of IgIV has been es tab lished in clud ing re place mentther apy in an ti body de fi ciency states, im mune throm bo cy -topenic pur pura and Ka wa saki dis ease. Other con di tionswere listed in which the ef fi cacy of IgIV was not yet es tab -lished. Based on the qual ity of avail able data, these lat ter con -di tions were fur ther di vided into those in which IgIV wouldproba bly or pos si bly prove to be ef fi ca cious. The com mit teere solved to up date the state ment as fur ther stud ies on the use of IgIV be came avail able.

In the three years since pub li ca tion of the guide lines, sev -eral stud ies of the ef fi cacy of IgIV ther apy have been re -ported. These stud ies have led the com mit tee to mod ify itsrec om men da tions. Well con trolled stud ies were pub lishedevalu at ing the use of IgIV in adults with Guillain- Barré syn -drome and other poly neu ro pathies (2,3). In pa tients withGuillain- Barré syn drome, re cov ery was im proved and has -tened by IgIV ther apy, and there were fewer com pli ca tionsand de creased need for ar ti fi cial ven ti la tion. An other well de -signed study in adults showed a sig nifi cant bene fit of IgIV fortreat ment of re frac tory der mato myo si tis (4).

A large mul ti cen tred, pla cebo con trolled, double- blindstudy of IgIV ther apy in chil dren with symp to matic hu man im -mu no de fi ciency vi rus (HIV) in fec tion dem on strated that pro -phy lac tic use of IgIV in creased the time free from se ri ousbac te rial in fec tion and mi nor bac te rial and vi ral in fec tions(5,6). The study was lim ited to chil dren un der 13 years of agewith out he mo philia; most were un der five years of age andhad ac quired HIV in fec tion by ver ti cal trans mis sion from in -fected moth ers. The pro tec tive ef fect of IgIV was lim ited to

chil dren who en tered the study with CD4 counts of 0.2x109/Lor more; there were too few chil dren with lower CD4 counts toshow any bene fi cial ef fect, or there may be no ef fect in thisgroup. Ir re spec tive of CD4 counts, there was no sig nifi cant ef -fect of IgIV ther apy on over all mor tal ity. More re cently, an otherlarge multi centred, ran dom ized, pla cebo con trolled, double- blind study dem on strated a bene fi cial ef fect of pro phy lac ticIgIV ther apy only in HIV-i nfected chil dren who were not re ceiv -ing trimethoprim- sulphamethoxazole ther apy (7). The authors hy pothe sized that lower rates of zi do vu dine use andtrimethoprim- sulphamethoxazole pro phy laxis for Pneu mo -cys tis car inii pneu mo nia in the ear lier study may have con trib -uted to the dif fer ences in the find ings.

Use of IgIV pro phy lac ti cally to pre vent in fec tions in lowbirth weight neo nates re mains con tro ver sial. The re sults offour pla cebo con trolled, double- blind stud ies have re centlybeen re ported. One study dem on strated a de creased risk ofno so comial in fec tion in pre ma ture in fants with birth weightsbe tween 500 and 1750 g, al though mor bid ity and mor tal itywere not af fected (8). Two other smaller stud ies failed to show a bene fi cial ef fect (9,10). The most re cently re ported study, alarge mul ti cen tred pla cebo con trolled study, also showed nobene fit of IgIV in pre vent ing no so comial in fec tions in in fantsweigh ing be tween 500 and 1500 g (11). This study noted alower in ci dence in the rate of no so comial in fec tions in bothtreated and un treated par tici pants than re ported in the ear lierstudy by Baker et al (8). Of par ticu lar con cern is the higher as -so cia tion of ne cro tiz ing en te ro co li tis in neo nates in fused withIgIV re ported in two of the stud ies (9,11).

The use of IgIV in pe di at ric bone mar row trans plant cen -tres is be com ing rou tine (12), al though data sup port ing its use are scarce. Most stud ies have dem on strated a bene fi cial ef -fect of IgIV in the pre ven tion of cy tomega lovi rus (CMV) in fec -tions in CMV-neg ative re cipi ents of bone mar row trans plants; a re cent meta- analysis sup ported these con clu sions (13). How -ever, an other study failed to show any in cre mental bene fit ofIgIV pro phy laxis com pared with use of CMV sero nega tiveblood prod ucts in bone mar row trans plant pa tients, al thoughthe power of the study was small (14). Other bene fits weresug gested in the IgIV treated pa tients in clud ing a de crease inGram- negative sep ti ce mia and lo cal in fec tions (15), non-CMV

vi ral in fec tions and over all deaths re lated to in fec tion (14) andnon-CMV in ter sti tial pneu mo nia (13). A de crease in graft-

11 CAN J INFECT DIS VOL 6 NO 1 JANU ARY/FEB RU ARY 1995

All material presented in Pediatric Infectious DiseaseNotes has been reviewed and approved by the chairperson,Canadian Pediatric Society Board representative andmembers of the Canadian Pediatric Society Committee onInfectious Diseases and Im mu ni za tion

Cor re spon dence and re prints: In fec tious Dis eases and Im -mu ni za tion Com mit tee, Ca na dian Pae di at ric So ci ety, 401Smyth Rd, Ot tawa, ON K1H 8L1. Tele phone (613) 737- 2728,Fax (613) 737-2794

PAEDIATRIC IN FEC TIOUS DIS EASE NOTES

versus- host dis ease was shown in IgIV treated pa tients (14),al though this bene fit was only ob served in pa tients older than20 years (15).

The in creased use of IgIV has height ened our rec og ni tionof the range of as so ci ated ad verse events, sev eral of whichhave been re ported since the origi nal com mit tee rec om men -da tions (1). The in ci dence of asep tic men in gi tis fol low ing IgIVin fu sion may be higher than pre vi ously thought, par ticu larlywith in fu sion at very high doses (2 g/kg) (16,17). Non-A,non-B hepa ti tis had not pre vi ously been re ported in prod uctsli censed in North Amer ica; how ever, cases of hepa ti tis C have now been as so ci ated with IgIV from one manu fac turer in theUnited States dur ing a brief pe riod in 1993 (18). Additionalmeth ods of vi ral in ac ti va tion used by other manufac tur ersshould re duce this risk (19); how ever, be cause of the risk oftrans mis sion of as yet un known blood-borne in fec tions, IgIVshould be used only if there is a clear in di ca tion. Fur ther more,our un der stand ing is in creas ing of the po ten tial ef fect of highdoses of IgIV on the re sponse to live vi rus vac cines, par ticu larlymea sles. In the origi nal com mit tee rec om men da tions, a de lay of mea sles im mu ni za tion for three months af ter IgIV in fu sion wassug gested. More re cent rec om men da tions sug gest a de lay offrom three to 11 months de pend ing on the prod uct and dose ofim mune globu lin given (20,21).

Based on these ad di tional data, the In fec tious Dis easesand Im mu ni za tion Com mit tee be lieves that there is suf fi cientin for ma tion to mod ify the pre vi ously pub lished guide lines (1).The com mit tee now con sid ers IgIV ther apy of prob able(rather than pos si ble) ef fi cacy for treat ment of Guillain- Barrésyn drome, re frac tory der mato myo si tis and for pro phy laxis forCMV in fec tions af ter bone mar row trans plan ta tion. In con trast,re cent data are less sup por tive of rou tine use of IgIV for pro -phy laxis against no so comial in fec tions in low birth weightneo nates; there fore, the com mit tee now con sid ers this use ofpos si ble ef fi cacy (rather than prob able ef fi cacy). Be cause ofcon flict ing data, the com mit tee con tin ues to con sider as prob -able ef fi cacy the use of IgIV in chil dren with HIV in fec tion andin chil dren who re ceive a bone mar row or or gan trans plant.

REF ER ENCES1. Infectious Diseases and Immunization Committee, Canadian

Paediatric Society. Intravenous immune globulin use in children. Can Med Assoc J 1992;146:121-4.

2. van der Meché FGA, Schmitz PIM, The Dutch Guillain-BarréStudy Group. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome. NEngl J Med 1992;326:1123-9.

3. van Doorn PA, Brand A, Strengers PFW, Meulstee J, Vermeulen M. High-dose intravenous immunoglobulin treatment in chronicinflammatory demyelinating polyneuropathy: a double-blind,placebo-controlled, crossover study. Neurology 1990;40:209-12.

4. Dalakas MC, Illa I, Dambrosia JM, et al. A controlled trial ofhigh-dose intravenous immune globulin infusions as treatmentfor dermatomyositis. N Engl J Med 1993;329:1993-2000.

5. The National Institute of Child Health and Human DevelopmentIntravenous Immunoglobulin Study Group. Intravenous immuneglobulin for the prevention of bacterial infections in children withsymptomatic human immunodeficiency virus infection. N Engl JMed 1991;325:73-80.

6. Mofenson LM, Moye J Jr, Bethel J, et al. Prophylactic

intravenous immunoglobulin in HIV-infected children with CD4+

counts of 0.20x109/L or more. JAMA 1992;268:483-8.7. Spector SA, Gelber RD, McGrath N, et al. A controlled trial of

intravenous immune globulin for the prevention of seriousbacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection. N Engl J Med1994;331:1181-7.

8. Baker CJ, Melish ME, Hall RT, et al. Intravenous immuneglobulin for the prevention of nosocomial infection inlow-birth-weight neonates. N Engl J Med 1992;327:213-9.

9. Magny JF, Bremard-Oury C, Brault D, et al. Intravenousimmunoglobulin therapy for prevention of infection in high-riskpremature infants: report of a multicenter, double-blind study.Pediatrics 1991;88:437-43.

10. Kinney J, Mundorf L, Gleason C. Efficacy and pharmacokineticsof intravenous immune globulin administration to high-riskneonates. Am J Dis Child 1991;145:1233-8.

11. Fanaroff AA, Korones SB, Wright LL, et al. A controlled trial ofintravenous immune globulin to reduce nosocomial infections invery low-birth-weight infants. N Engl J Med 1994;330:1107-13.

12. Casper JT, Sedmark G, Harris RE, et al. Intravenousimmunoglobulin: use in pediatric bone marrow transplantation.Semin Hematol 1992;29(Suppl 2):100-5.

13. Bass EB, Powe NR, Goodman SN, et al. Efficacy of immuneglobulin in preventing complications of bone marrowtransplantation: a meta-analysis. Bone Marrow Transplant1993;12:273-82.

14. Winston DJ, Ho WG, Bartoni K, Champlin RE. Intravenousimmunoglobulin and CMV-seronegative blood products forprevention of CMV infection and disease in bone marrowtransplant recipients. Bone Marrow Transplant 1993;12:283-8.

15. Sullivan KM, Kopecky KJ, Jocom J, et al. Immunomodulatoryand antimicrobial efficacy of intravenous immunoglobulin inbone marrow transplantation. N Engl J Med 1990;323:705-12.

16. Sekul EA, Cupler EJ, Dalakas MC. Aseptic meningitis associated with high-dose intravenous immunoglobulin therapy: frequencyand risk factors. Ann Intern Med 1994;121:259-62.

17. Scribner CL, Kapit RM, Phillips ET, Rickles NM. Asepticmeningitis and intravenous immunoglobulin therapy. Ann InternMed 1994;121:305-6.

18. Schneider L, Geha R. Outbreak of hepatitis C associated withintravenous immunoglobulin administration – United States,October 1993–June 1994. MMWR 1994;43;505-9.

19. Edwards CA, Piet NPJ, Chin S, Horowitz B. Tri(n butyl)phosphate detergent treatment of licensed therapeutic andexperimental blood derivatives. Vox Sang 1987;52:53-9.

20. Committee on Infectious Diseases. Recommended timing ofroutine measles immunization for children who have recentlyreceived immune globulin preparations. Pediatrics1994;93:682-5.

21. National Advisory Committee on Immunization. CanadianImmunization Guide, 4th edn. Ottawa: Health Canada,1993:14-5.

Ca na dian Pae di at ric So ci etyIn fec tious Dis eases and Im mu ni za tion Com mit tee

Mem bers: Mi chael Hall (di rec tor re spon si ble) , St John’s, New found land; Noni E Mac Don ald (chair), De part ment of

Pe di at rics, Chil dren’s Hos pi tal of East ern On tario, Ot tawa, On tario; Scott A Halp erin (prin ci pal author), Izaak Wal ton

Kil lam Chil dren’s Hos pi tal, Hali fax, Nova Sco tia; Wil liam Al brit ton, Pro vin cial Labo ra tory of Pub lic Health, Ed mon -ton, Al berta; François Boucher, Dépar te ment de pédia trie, Cen trehos pi tal ier de l’U ni ver sité La val, Ste- Foy, Qué bec; Gil les Delage,

Ad joint médi cal, Serv ice de trans fu sion de sang de la Croix- Rouge ca na di enne, Cen tre de

Mon tréal, Mon tréal, Qué bec; Eliza beth Ford- Jones, Di vi sion of In fec tious Dis ease, The Hos pi tal for Sick Chil dren, To -

ronto, On tario; Su san King, Di vi sion of In fec tious Dis ease,

In fec tious dis ease notes

CAN J INFECT DIS VOL 6 NO 1 JANU ARY/FEB RU ARY 1995 12

The Hos pi tal for Sick Chil dren, To ronto, On tario; David P Speert,Re search Cen tre, Van cou ver, Brit ish Co lum bia.

Ex- Officio Mem bers: Frank R Frie sen (Chair, Com mit tee on Com -mit tees), Mani toba Clinic, Win ni peg, Mani toba.

Con sult ants: Ron ald Gold, Di vi sion of In fec tious Dis ease, TheHos pi tal for Sick Chil dren, To ronto, On tario;

Vic tor Marches sault, De part ment of Pe di at rics, Chil dren’s Hos pi tal of East ern On tario, Ot tawa, On tario.

Li ai sons: Pub lic Health, Jac que line Carl son, Dis ease Con trol and

Epi de mi ol ogy, Pub lic Health Branch, To ronto, On tario; Ameri canAcad emy of Pe di at rics, Larry Pick er ing, East ern

Vir ginia Medi cal School, Chil dren’s Hos pi tal of the King’s Daugh -ters, Nor folk, Vir ginia; Cen tre for Vac cine Evalua tion, David

Scheifele, Di vi sion of In fec tious Dis eases, Re search Cen tre, BC’ s Chil dren’s Hos pi tal, Van cou ver, Brit ish

Co lum bia; Epi de mi ol ogy, John Wa ters, Al berta Health, Com mu ni -ca ble Dis ease Con trol, Ed mon ton, Al berta

In fec tious dis ease notes

13 CAN J INFECT DIS VOL 6 NO 1 JANU ARY/FEB RU ARY 1995

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Update: Intravenous immune globulin in childrendownloads.hindawi.com/journals/cjidmm/1995/198693.pdf · mu no de fi ciency vi rus (HIV) in fec tion dem on strated that pro - phy lac