Post-Exposure Rabies Regimens for Immunodeficiency Patients · 2016. 9. 13. · receive rabies...
Transcript of Post-Exposure Rabies Regimens for Immunodeficiency Patients · 2016. 9. 13. · receive rabies...
Post-Exposure Rabies Regimens for
Immunodeficiency Patients
Suda Punrin, MD.
Immunodeficiency
• Primary
• Secondary
Chinen J, Shearer WT. J Allergy Clin Immunol 2010;125:S195-203
Secondary (acquired) immunodeficiency
Rabies vaccination
• HIV infection
• Malignancy
• Transplantation
• Immunosuppressive drugs
Rabies vaccination
• HIV infection
• Malignancy
• Transplantation
• Immunosuppressive drugs
Deshpande, 1999 ESSEN IM
57% of symptomatic HIV-infected pts had
Nab 0.5
Jaijareonsup, 1999 TRC-ID + ERIG
4/9 of HIV-infected pts (CD4+ 316-950)
had Nab 0.5
Thisayakorn, 2000 IM PrEP in HIV-
infected children CD4+ < 15% had
lower Nab
Tantawichien, 2001 Double TRC-ID +
HRIG HIV-infected pts
(CD4+ 25 – 199)had Nab < 0.5
Tantawichien, 2009
Double ESSEN+adjuvant HIV-infected pts CD4+ < 100 had
Nab < 0.5
Sirikwin, 2009
Modified 8-sites ID HIV-infected pts CD4+ 69-190 on
HAART All had Nab 0.5
Gelinck, 2009 IM Day 0,84
HIV-infected pts CD4+ 353 -772
All had Nab 0.5
Azzoni, 2012
IM Day 0,7,42,378 HIV-infected pts
on regular HAART had Nab 0.5
Clinical trials
1999 2000 2009 2012
HIV & Rabies vaccination
Nab; neutralizing antibody
Regimens Nab < 0.5 IU/mL Nab ≥ 0.5 IU/mL
5-dose IM (ESSEN)
- 43% symptomatic (CD4+ < 400) - 24% asymptomatic CD4+ ? Anti-retroviral therapy (ARV) ?
TRC-ID (2-2-2-0-1-1) + ERIG
55 % of CD4+ < 300
CD4+ > 300
Double doses TRC-ID (4-4-4-0-2-2) + HRIG
43% of CD4+ < 200
CD4+ > 200 All on ARV
Double doses ESSEN-IM (2-2-2-2-2) + Aluminium adjuvanted TT
5/7 (71 %) of CD4+ < 100 (4/7 patient on ARV)
CD4+ > 250 2/7 (29%) of CD4+ > 100 (One patient on ARV)
Modified 8-site ID (8-8-8-8-8)
81% on ARV 66% had CD4+ > 200 One had CD4+ 69
HIV on ARV
Thai &WHO-approved regimens
Double doses (x2)
Modified 8-site ID
Double doses ESSEN +
aluminium adjuvanted
CD4+ > 300
CD4+ 200-300
CD4+ 100-200
NA
CD4+ < 100
?
โดนกัดมาอีกแล้ว !
Booster Re-start
Abbas AK et al. Cellular and Molecular immunology. Eighth Edition
0
5
10
15
20
25
30
35
D0 D7 D14 D28 D90 D180 D360
HIV Booster IM day 0,3
0.5
Nab ≥ 0.5 IU/mL since day 7 - 360 97% on HAART
Median CD4+ = 489
(range 94 – 1120)
GMT (IU/mL)
Punrin S, et. al. Proceedings of the 22th ECCMID. 31 March - 3 April 2012, London, United Kingdom.
Remarks
• One AIDS participants, who was vaccinated since seronegativity, had anamnestic response to booster injection
• One patients who had CD4+ count < 100, somehow, had the remaining seroprotective titers from the prior immunization
Remarks
• An AIDS patient who antecedently failed to seroconvert after PEP could evoke the immunologic memory response after quantitative CD4+ count recovery by HAART
Cell-mediated immune responses to intradermal rabies vaccination
Phanuphak P et al. Asian Pacific Journal of Allergy and Immunology 1987;5:33-7 Ratanavongsiri J, et. al. Asian Pac J Allergy Immunol 1985;3:187-90
Intradermal Intramuscular
0
5
10
15
20
25
30
35
D 0 D 7 D 14
Gr 1: 4 site-ID
Gr 2: IM Day 0,3
GMT (IU/mL)
Esp, CD4+ ≥ 500 (p=0.03)
100 % on HAART, median CD4+ = 622, HIV RNA < 20 copies/mL
Serrano-Villar S, et. al. Lancet HIV 2015;2:76-7 Lu W, et. al. J Int AIDS Soc 2015;18:20052
CD4/CD8 ratio: a re-emerging biomarker for HIV
A low ratio is associated with T cell activation, senescence, dysfunction and chronic inflammation
CD8+
CD4+
CD4+/CD8+ ratio & Nab day 7
Being primary rabies immunized during AIDS conditions had affected subsequent booster vaccination despite quantitative CD4+ T-cell recovery
Remarks
• Concept of pre-immunization of HIV-infected persons before the immunosuppression progressed might be considerably applicable to those at greatest risk
Longevity of Nab in HIV
• Four years interval from the latest immunization, 86.8% of patients had Nab > 0.5 IU/ml
• One volunteer had found endurance of seroconversion for 15 years
• However, a few patients who recently got rabies vaccine within one year could not maintain acceptable seroprotective level
Selected cases of HIV patients might receive rabies booster vaccination if…
• Asymptomatic, on HAART, CD4+ > 200
• No opportunistic infections
• No severe chronic medical conditions
• No other immunosuppressive conditions
• Received complete post-exposure rabies prophylaxis with cell-cultured vaccine within 10 years
Suggestion for rabies booster vaccination
• Only single visit 4-site ID and conventional IM day 0 and 3 regimens could be used
• Booster with full schedule regimens for every exposure
• Wound treatment is still the mandatory
Safety of rabies vaccination in HIV-infected patients
• Inactivated vaccine
• No serious adverse reactions
• No long term effect to CD4+ and HIV RNA level
• No effect to HIV progression
WHO Expert Consultation on Rabies. Second report. 2013;1-139
WHO recommendation
• Wound treatment
• Local infiltration of RIG
• Five IM doses of rabies vaccine
(asymptomatic, on HAART, recent CD4+ > 300)*
• Check rabies neutralizing antibody
• Observe responsible cat or dog for 10 days*
• When in doubt, consult specialist
* Suda’s opinions
Rabies vaccination
• HIV infection
• Malignancy
• Transplantation
• Immunosuppressive drugs
Hay E, et. al. JAMA 2001;285:166-7 Rahimi P, et. al. PLoS One 2015;10:e0139171
Kopel E, et. al. Emerg Infect Dis 2012;18:1493-5 Wiwanitkit V. Iran J Cancer Prev 2014;7:105-6
Malignancy Regimens
Lymphoma (4) ESSEN IM + HRIG ± Double doses ESSEN + HRIG
Acute myeloid leukemia (1) Double dose IM day 0 2-1-1-1-1 (no Nab)
Malignancy (non-specific) (5) ESSEN IM
CA Breast stage IV (Brain & bone metastasis)
On radiation & received corticosteroids
I ESSEN IM + HRIG II Booster IM Day 0,3
Nab (IU/ml)
D 0 = negative
D 7 = 0.53
D 14 = 0.28 **
D 28 = 0.28 **
D 60 = > 0.5
D 74 = > 0.5
D 120 = > 0.5
Stop radiation, Prednisolone 10 mg/day
Suda Punrin, et. al. Proceedings of 23th ECCMID, 27 - 30 April 2013, Berlin, Germany
Non-Hodgkin lymphoma stage IV, in remission
- Completed R-CHOP course 3 mo ago
- Received PEP x2 times before diagnosis of NHLs
I Booster IM Day 0,3 II Booster IM Day 0,3
Nab (IU/ml) D 0 = 2.41 D 14 = 2.52 D 90 = 2.73 D 104 = 3.22
Recurrence of NHLs in the next 4 months
Suda Punrin, et. al. Proceedings of 23th ECCMID, 27 - 30 April 2013, Berlin, Germany
Severity
Stage Treatment
Immune status
Rabies vaccination
• HIV infection
• Malignancy
• Transplantation
• Immunosuppressive drugs
Rubin LG. et. al. Clin Infect Dis 2013:1-57 Eibl M., Wolf H. Immunotherapy 2015;7:1273–92
Vora M. et. al. Transpl Infect Dis 2015;17:389–95
ESSEN IM (1-1-1-1-1) + RIG
Rabies vaccination
• HIV infection
• Malignancy
• Transplantation
• Immunosuppressive drugs
Rubin LG. et. al. Clin Infect Dis 2013:1-57 Eibl M., Wolf H. Immunotherapy 2015;7:1273–92
อรพิน เลิศวรรณวิทย์ วิทยานิพนธ์ปริญญามหาบัณฑิต ภาควิชาอายุรศาสตร์ คณะแพทยศาสตร์ จุฬาลงกรณ์มหาวิทยาลัย 2555
การตอบสนองทางภูมิคุ้มกันต่อการได้รับวัคซีนป้องกันโรคพิษสุนัขบ้า ในอาสาสมัครที่ได้รับยาสเตียรอยด ์
Modified TRC-ID (2-2-2-0-2) On prednisolone ≥ 20 mg/day at least 3 weeks or
accumulative dose ≥ 700 mg & receiving 10 mg/day Autoimmune hemolytic anemia, nephrotic syndrome, hypereosinophilia, Pemphigus vulgaris, Pemphigus foliaceus, Alopecia areata, ITP, COPD, Lupus profundus, Evan syndrome and bullous LE, SLE, rheumatoid arthritis
81.3% of pateints had Nab > 0.5 IU/mL โรคประจ าตัวในกลุ่มโรคผิวหนัง และ ระยะเวลาในการรับประทานยาสเตียรอยด์ที่มากกว่า 1 ปี สัมพันธ์กับระดับ Nab ที่น้อยกว่า 0.5 IU/mL
U.S. ACIP recommendation
• Immunosuppressive agents should not be administered during PEP
• Nab should be checked to ensure that acceptable antibody response has developed
Manning SE, et al. MMWR Recomm Rep 2008;57:1-28
WHO Expert Consultation on Rabies. Second report. 2013;1-139
WHO recommendation
• Wound treatment
• Local infiltration of RIG
• Five IM doses of rabies vaccine
• Check rabies neutralizing antibody
• When in doubt, consult specialist
Acknowledgements
Thank you for your attention