the common viral infections in immunocomprimised patients

1. PRSESENTED BY :TASNEEM ABDUL GAFOOR
PHARMD INTERN

2. INTRODUCTION
 Immunosuppressive therapy (IMT) is the cornerstone of treatment in the
posttransplantation setting.
 Immunosuppressive drugs used following transplantation to reduce the risk of
rejection results in increased risk of infection

3. Most commonly seen viral infections in Post transplant recipients or
immuncomprimised patients
 HBV
 VARICELLA ZOSTER VIRUS
 HERPES SIMPLEX VIRUS
 HCV
 RESPIRATORY VIRUSES
 HUMAN PAPILOMA VIRUS
 BK POLYOMA VIRUS VIRUS
 CYTOMEGALOVIRUS
 EPSTEIN-BARR VIRUS

4.  Viruses can establish persistent infections in immunocompetent hosts, which can be
divided into.
chronic latent
Continuous prolonged viral replication maintenance of the viral genome without
and shredding are observed replication(herpesvirus and
polyomaviruses)
(e.g., HBV and HCV)
 Constant host immune surveillance are able to block reactivation of latent infections.
 Receiving immunosuppressive agents following solid organ transplantation (SOT) can
cause viral reactivation, particularly in the first six months after transplant.

5.  CMV infection can directly and indirectly affect the kidney allograft.
Sources of CMV infection in transplant recipients include
 latent reactivation
 donor-transmitted virus,
 and virus present in donor leukocytes.
Direct effects Indirect effects
CMV syndrome (e.g., fever,
fatigue, myalgia, and leucopenia)
or
CMV diseases (e.g., pneumonitis,
gastritis, duodenitis, or colitis).
 acute or chronic graft injuries,
 allograft rejection,
 poor graft survival, and
 Opportunistic infections
especially invasive fungal
infections

6. The risk factors for CMV infection are:
 Low lymphocyte count/complement /NK count ,
 Low IgG hypogammaglobulinemia ,
 donor-recipient CMV serology mismatch, and
 use of lymphocyte-depleting agents .
 Most cases of symptomatic CMV infection can be characterized by
 a episodic fever attacks for a period of 2 to 4 weeks,
 arthralgias,
 fatigue,
 anorexia,
 abdominal pain and diarrhea.
 Current diagnostic strategies rely on the detection of CMV viremia; antibody testing
and culture

7.  The two major strategies for CMV prevention are:
 Antiviral prophylaxis
 Preemptive therapy
Therapeutic options for ganciclovir resistant CMV are limited.
 Foscarnet -1st line treatment
 Cidofovir – 2nd line treatment.
Antiviral prophylaxis Preemptive therapy
• valganciclovir (900
mgOD)
• IV ganciclovir (5 mg/kg
every 24 h).
• oral ganciclovir 1g TDS)
•Intravenous immunoglobulin
(IVIG)
• valganciclovir (900 mg
twice daily)
•IV ganciclovir (5 mg/kg
every 12 h)

8.  Gamma herpesvirus and it maintains latency.
 uncontrolled EBV-driven B-cell proliferation
 posttransplant lymphoproliferative disease (PTLD).
 EBV infection causes a mononucleosis-type syndrome presenting as a lymphocytosis
with or without lymphadenopathy or pharyngitis .
 PTLD has increased extranodal involvement
 Risk factors for PTLD include
 type of transplanted organ;
 EBV mismatch; and
 Type of induction immunosuppressive therapy( antithymocyte globulin, muromonab-
CD3, and belatacept

9.  Treatment: Combinations of
 anti-B cell therapy (anti-CD20; Rituximab)
 chemotherapy (CHOP)
 irradiation (for central nervous system disease)
 and/or adoptive immunotherapy with stimulated T cells.
 BKV remains latent in renal tubular epithelial cells.
BKV infection after transplantation can cause
 hemorrhagic cystitis
 tubulointerstitial nephritis
 ureteric stricture,
 BKVassociated nephropathy (BKVAN), and
 premature graft failure.

10. Risk factors
 Deceased donor
 mismatched BKV-specific antibody of donor/recipient (D+/R-),
 older age of the recipient
 tacrolimus-mycophenolic(MFA>1g/day) use,
 or retransplantation after graft loss due to BKVAN
Diagnosis:
 BK viruria is sensitive for detecting active BKV infection
 BKV DNA in plasma may represent a better indicator for nephropathy, (when
plasma BKV load is >4 log10 copies/mL or when there is impaired renal allograft
function)
 The gold standard for diagnosing BKVAN is kidney histology including
tubulointerstitial nephritis with cytopathic changes and positive antibodies generally
targeting BKV antigens

11.  Treatment for BKVAN is to reduce immunosuppressive drugs.
This can be done by
 withdrawing mycophenolate mofetil or tacrolimus,
 replacing tacrolimus with cyclosporine
 Cidofovir(0.25 to 1.0 mg/ kg)has been effectively used to treat BKVAN in kidney
transplant recipients at 1 wk -3wk intervals .
 Leflunomide is another alternative
 Ciprofloxacin has antiviral activity against BKV
 Also Intravenous Ig (IVIG) preparations administeration(0.2-2.0 g/kg) in
conjunction with reduced immunosuppressive drugs , leflunomide, ciprofloxacin.

12.  First line
CIDOFOVIR :
0.5-1.5mg/kg/dose1-3times/week
3-5mg/kg/dose every 1-2 wk with
concomitant probencid)
• LD-100mg/day
for 5d;
• MD-40mg/d
LEFLUNOMIDE
• 250mg BD for 1
month
CIPROFLOXACINN
• 0.2-2.0 g/kg
IVIG
BKVAN–KIDNEY
TRANSPLANT
0.25 to 1.0 mg/ kg 1 wk
-3wk intervals
ALTERNATIVES

13.  The HBV vaccine should be offered to patients with negative results for all
serological markers for HBV infection.( HBsAg, anti-HBc and HBV surface
antibody (anti-HBs) )
 If patients are already on IMT, vaccination and testing for serological immunity is
recommended 1–2 months after administration of the vaccines last dose.
 Anti-HBs concentration of ≥10 mIU/ml is considered as a reliable indicator of
protection against infection
According to the current guidelines produced by ECCO, AASLD and (EASL)
 antiviral prophylaxis is not required in recipients with anti-HBs titer above 10 IU/L;
 however, one-year lamivudine prophylaxis may be considered in recipients with
negative antiHBs. and patients who are HBsAgpositive

14.  Optimal therapy -use of at least one antiviral active against Hepatitis B; currently
lamivudine is most commonly used.
 Alternative include
 IFN
 Adefovir
 entecavir and telbivudine.
 HBsAgnegative/anti-HBc-positive patients should be monitored with
aminotransferase and HBV-DNA levels
 Antiviral therapy should be introduced when HBV-DNA levels become detectable.
 The consensus guidelines still recommend
 indefinite entecavir or tenofovir prophylaxis in all recipients
 hepatitis B immune globulin (HBIG) should be considered in recipients with anti-
HBs < 100 U/L

16.  Liver disease /Viral Diseases in Transplant and Immunocompromised Patients
secondary to chronic HCV infection is an important cause of morbidity and
mortality in dialysis patients and kidney transplant recipients.
 Initial screening for anti-HCV should be performed in all transplant candidates.
 If the patient has a positive anti HCV result, then HCV viral load should be
done.
 The prolonged suppressive therapy aggravates liver function
 All immunosuppressed and HIV infected patients should be screened for HCV
infection using sensitive immunoassay(ELISA)

17.  HCV +ve patients should be tested for HCV RNA using RT PCR. (confirm active
infection)
 In the past, the treatment options for HCV in transplant recipients were limited
because pegylated-interferon based regimens increased the rate of acute allograft
rejection.
 Currently, the standard treatment –
DAAs

NS5B polymerase
inhibitors
NS5Ainhibitors NS3/4A protease
inhibitors
Sofosbuvir
Dasabuvir
Daclatasvir
Elbasvir
Ledipasvir
Ombitasvir
Pibrentasvir
velpatasvir
Glecaprevir
Grazoprevir
Paritaprevir
Simeprevir
voxilaprevir

18.  DAA REGIMEN
LDV/SOF ±
RBV
SOF/VEL/VOX
EBR/GZR ±
RBV
GLE/PIB
SOF/VEL ±
RBV

19.  VZV is alpha herpes viruses.
 Infection is caused by reactivation of latent virus.
 VZV occurs as early as 1 to 6 month post transplant.
 Primary infection with varicella zoster virus (VZV) causes chickenpox,
characterized by vesicular cutaneous lesions and fever.
 Reactivation of latent VZV results in herpes zoster virus (HZV), producing a
painful, vesicular dermatomal rash .
 Immunosuppression and age > 50 years old increases the risk of disseminated
disease, chronic mucocutaneous infection and can lead to HZV encephalitis,
pneumonia, hepatitis
 Herpes zoster is characterized by vesicular rash units all over the corresponding
nerve

20.  It is a frequent infectious complication during the first four years after the
transplantation
 VZV-related complications :disseminated disease and postherpetic neuralgia.
 To determine the risks of VZV primary infection or, all patients considered to
undergo serologic testing (ELISA anti VZV IgG)
 Viral culture is specific and can help distinguish VZV from other herpesvirus
pathogens (HSV).
 To prevent complicated VZV infection:
 post-exposure passive antibody prophylaxis in the form of varicella zoster
immunoglobulin (VZIG)
 active vaccination

21.  Primary varicella should be treated with IV Acyclovir, especially within 24 hours of
rash onset.
 VZV immunoglobulin (VZIG) have been used in severe infection.
 Patients with disseminated or organ invasive herpes zoster should be treated with IV
acyclovir.
 Active immunization with a two-dose series of live varicella vaccine is advised by
ECCO, at least 3 weeks before introducing IMT.
 Localized nonsevere dermatomal herpes zoster can be treated with oral acyclovir,
valacyclovir or famcyclovir .

22.  Herpes simplex virus type 1 (HSV1) –childhood
 herpes simplex virus type 2 (HSV2)-sexual contact
 HSV occurs in 1st month of post transplant period
 Symptomatic disease : 1st episode that heals in 10–21 days,
establishment of latency
risk of subsequent episodes of reactivation.
 Mucocutaneous lesions are the majority of HSV disease, mainly with orolabial and
anogenital localizations

23.  Diagnosis
 ELISA anti HSV1 IgG and anti HSV2 IgG to document prior exposure to the viruses.
 Viral culture
 Direct fluorescent antibody test
 Treatment:
 Acyclovir is the drug of choice for treatment of HSV infections
 Transplant patients with mucocutaneous lesions :IV acyclovir (5 mg/kg/dose given
every 8 hours) for 7–14 days, or oral acyclovir
 alternative like valacyclovir or famcyclovir.
 Disseminated infections / herpes simplex encephalitis :IV acyclovir (10 mg/ kg/dose
given every 8 hours) for 7–14 days.
 Acyclovir can also be used for prophylaxis of the infection to prevent reactivation

24. The respiratory viruses, including
 Adenovirus
 Respiratory Syncytial virus (RSV)
 Influenza virus
 Rhinovirus (HRV
 Parainfluenza virus (PIV)
 Human Metapneumovirus (hMPV)
 Immunocompromized patients often have atypical presentation of respiratory infections
and viral shedding can be prolonged.
 Adenoviruses are usually in latent condition becomes clinically manifested after
reactivation .
 HRV is probably the most common respiratory viral pathogen in the upper and lower
respiratory tract in transplant recipients
 Diagnosis of the respiratory viruses can be achieved by the combination of serology,
virus culture, antigen detection, nucleic acid testing, and histopathology.

25.  Rapid antigen detection using several different techniques is available for Influenza,
RSV, and Adenovirus
 Treatment depends on the etiological agent.
 RSV Infection: combination therapy with aerosolized ribavirin and IVIG appears
to have the greatest benefit .
 PIV and hMPV infections :oral, aerosolized, or IV ribavirin with IVIG
 Adenovirus infections :Cidofovir, Vidarabin, and Gancyclovir.
 Rhinovirus infections :Pleconaril and 3C-protease inhibitors. Topical interferon
might be efficacious in moderating viral shedding and symptoms .
 severe Influenza :both M2 inhibitors (Rimantadin and Amantadin) and
Neuraminidase inhibitors (Relenza and Tamiflu)

26. • aerosolized RIBAVIRIN(mechanically ventilated continous 6g over
12-18hrs daily;
• non mechanically ventilated:intermittent 6 g over 2-6hr q8hrs) and
IVIG appears to have the greatest benefit .
RSV
INFECTION:
• :oral, aerosolized, or IV ribavirin(600-800mg BD/TDS daily)
with IVIG
PIV AND HMPV
INFECTIONS
• CIDOFOVIR(5mg/kg/dose once weekly-5mg/kg/dose every
other week)
• RIBAVARIN
ADENOVIRUS
INFECTIONS
RHINOVIRUS
INFECTIONS
:PLECONARIL 400mg OD 5 DAYS
Topical interferon might be efficacious in moderating viral shedding and
symptoms
M2 inhibitors (RIMANTADIN 100mg BD 5-7days and
AMANTADIN200mg OD 5 days)
Neuraminidase inhibitors (OSELTAMIVIR 75mg BD 10days
ZANAMAVIR IV 600mg)
INFLUENZA

27.  In HIV-positive patients -Corticosteroids CD4 population and HIV viral load .
 Calcineurin inhibitors (tacrolimus/cyclosporine) and antiproliferative agent
(MMF)have well-documented antiretroviral effects
 ECCO guidelines; testing for HIV active infection by HIV p24 antigen and antibody,
prior to immunomodulators and anti-TNF agents .
 If active infection is diagnosed, HAART(highly active antiretroviral therapy) should
be started before IMT .
 Treatment of rejection with cytolytic agents such as thymoglobulin may result in
prolonged depression of CD4 counts and significant infection-related morbidity.
 Treatment for liver transplant HIV+ HBV:HBIG (first 5-7 Post T)_and antivirals
used in HBV(Lamivudine/Emtricitabane with Tenofovir)

30.  HPV infections :oral, skin, genital, and rectal lesions ranging from warts and
dysplasia to malignancy.
 The infection can be low risk, associated with anogenital warts or mild dysplasia, or
high risk, associated with cervical or anal neoplasia.
 Immunosuppressed post-transplant patients and those infected with HIV : risk
benign and malignant anogenital tumours mediated by HPV
 Thiopurines and cyclosporine -viral warts in organ transplant recipients.
 Women receiving IMT are high-risk according to the American college of
Obstetricians and Gynecologists (ACOG)
 Two prophylactic vaccines are available:
 Bivalent vaccine (Cervarix) for HPV16-18 subtypes
 Quadrivalent (Gardasil) for HPV6-11-16-18 genotypes.

31.  Treatment requires decreasing immunosuppression, topical, or surgical treatment.
 Topical immunotherapies such as imiquimod should be used.
 Cryotherapy: cutaneous warts using liquid nitrogen.
 Keratolytics: salicyluc acid and lactic acid
 Cidofovir limits HPV induced epithelial cell proliferation
 The 2012 CDC guidelines recommend either vaccinate routinely for females aged
11–12 years and between 13 and 26 years if missed at an earlier stage, and also for
males of the same age group.
 Only the quadrivalent vaccine has been approved for males.