New Emerging Pathogens in blood and blood components transfusion

Risk categories of emerging infections
dengue
HTLV I/II
Chickengunya
covid
corona virus
west nile virus
zika virus
ebola virus
cytomegalovirus
ebstein barr virus
parvovirus
bacteria
Yersinia
Pseudomonas
Staphylococcus epidermidis or Staphylococcus aureus-
Propionibacterium acnes
parasites- Babesia microti, Trypanosoma cruzi, and malaria (Plasmodium species).

1. New Emerging Pathogens Presenter- Dr. Shiny Moderator- Dr. Anshul Gupta

2. Introduction Emerging infections- defined as ‘those whose incidence has increased within the past two decades or threaten to increase in the near future’.  Emergence may be due to the evolution of an existing organism the spread of a new agent the recognition of an infection present in the population but has gone undetected the reappearance of a known infection after a decline in its incidence.

3. Risk categories of emerging infections

4. Emerging Viral Pathogens

5. Dengue Caused by- four arboviruses (DENV 1–4) belonging to the  Flavivirus  genus. Transmission- primarily by  Ae. aegypti   mosquitoes,   Ae. albopictus  is also a competent vector. Symptoms- wide range of outcomes, from asymptomatic infection to a fatal shock syndrome . Presents with onset of fever, rash, a severe headache, lumbosacral aching pain followed by muscle pain, bone pain, anorexia, nausea, vomiting, and weakness. Incubation period- 4 to 7 days following the bite of an infected mosquito. Diagnosis- NAT or viral antigen testing  Treatment & Prevention- Vaccines are in clinical trials. No definitive management, only supportive care. Donor deferral- for 6 months

6. HTLV-I/II C ausative agent of adult T-cell leukemia Prevalence- in Japan and The Caribbean. Has been associated with a neurological disorder called HTLV associated myelopathy Prevalence- among intravenous drug users Transmission- via infected lymphocytes T ransmitted vertically (breastfeeding), sexually (transmission from male to female more common), and parenterally (blood transfusion or IV drug abuse). Screening for HTLV-I began in 1988; a combined HTLV-I/II assay was approved 10 years later in 1998. Diagnosis- IFA and Western blot

7. HTLV-I/II Treatment- does not respond well to chemotherapy; mean survival time with acute ATL is <1 year. However, early treatment with corticosteroids appears to have some effect Donor criteria- There is no approved protocol for donor re-entry involving HTLV-infected donors

8. West Nile virus (WNV) single-stranded RNA lipid-enveloped virion Prevalence- common in S. Africa, Europe, N. America & West Asia Host- arthropod-borne virus involving the natural reservoir host (birds) and the intermediate host (mosquitos), which can infect a human. first detected in the United States in 1999 Symptoms- symptoms ranging from mild fever and headache to extensive rash, eye pain, vomiting, inflamed lymph nodes, prolonged lymphocytopenia, muscle weakness, disorientation, and even acute flaccid paralysis and poliomyelitis . The association of paralysis and poliomyelitis with WNV is recent. Incubation period- 3 to 14 days following the mosquito bite

9. WNV is capable of crossing the blood-brain barrier and can cause what is known as West Nile encephalitis, West Nile meningitis Testing for WNV began in 2003, and in 2009 the FDA published their final guidelines for testing all whole blood and component donor samples. Diagnosis- aMP -NAT or individual donor (ID-NAT) method. Identification by- IgM antibody to the WNV in serum and cerebrospinal fluid Donor criteria- The donor should be deferred from further donations for 120 days. Treatment- Once infected, there is no licensed treatment, only supportive therapy. West Nile virus (WNV)

10. Chikungunya Virus (CHIKV) single-stranded RNA virus of the family Togaviridae Prevalence- common in India and Africa . Transmission- the Aedes family S ymptoms - high fever, severe joint pain, headache, muscle pain, rash, and leukopenia. Meningoencephalitis has been described during an outbreak on Reunion Island in 2005 to 2007 Treatment/ Prevention- No medication for treatment and no vaccine for prevention. Theoretically, CHIKV could be spread through transfusion, but there have been no reported cases of CHIKV transmission through transfusion even during outbreaks.

11. Zika RNA virus and spread by the bite of an infected Aedes aegypti and A. albopictus Prevalence - Southeast Asia, Tropical Africa Transmission- via blood transfusion, from mother to fetus , and by sexual intercourse Symptoms- fever, rash, headache, joint and muscle pain, and redness of eyes. Clinical imp.- ZIKV has been associated with severe neurological complications including increased rates of microcephaly and fetal brain anomalies during pregnancy and Guillain-Barre syndrome. Donor criteria- FDA recommends- who have been infected with Zika not donate blood for 4 weeks. This includes those who have demonstrated symptoms or had sexual contact with people who have traveled to countries associated with transmission.

12. Zika Diagnosis- The Cobas Zika ID-NAT Prevention- Currently, there is no vaccine for Zika. Current trends- The FDA has established ZIKV as a transfusion transmitted infection. In August of 2016, the FDA released an updated guidance for the industry requiring testing of all donations with an individual donor nucleic acid test for ZIKV

13. EBOLA The virus was first described in 1976 near the Ebola River in the Congo. Prevalence- Central and western Africa Transmission- via exposure to blood or body fluids , contaminated needles, and infected primates. I ncubation period- 2 to 21 days. Symptoms- fever, headache, muscle and abdominal pain, fatigue, diarrhea, vomiting, and unexplained hemorrhaging. Prevention- no FDA approved vaccine to prevent Ebola.

14. EBOLA Donor criteria- FDA recommends an indefinite deferral for a donor with disease as well as an 8-week deferral from the date of his departure from an area with widespread transmission of Ebola virus Current trends- The CDC has characterized Ebola as a Category A bioterrorism agent/disease - an outbreak occurred in West Africa with nearly 29,000 suspected cases and 11,325 related deaths.

15. Coronavirus Symptoms- common cold to severe acute respiratory syndrome (SARS- CoV ) Incubation period- 1 to 14 days COVID 19 outbreak- SARS-CoV-2 Infectivity by viral RNA in plasma Donor criteria- donor deferral for 28 days from complete recovery from disease or travel/contact history & 14 days from COVID vaccination

16. Cytomegalovirus member of the herpesvirus group Once an individual is exposed, CMV can remain latent in the tissues and leukocytes for years , with reactivation occurring from a severe immune system impairment Those at the highest risk of a CMV infection are fetuses and immunocompromised individuals receiving allogeneic marrow transplants or solid organ transplants. The neonate may be exposed at the time of delivery, through breastfeeding, or through contact with seropositive individuals. Approximately 1% of all newborns are infected with CMV, but most are asymptomatic at birth

17. Cytomegalovirus Transmission- person to person through contact with infected body fluids , which may include urine, semen, saliva, blood, cervical secretions, and breast milk. CMV is the most frequently transmitted virus from mother to fetus. Detection- Antibodies formed to CMV last a lifetime and can be detected by ELISA Treatment- Currently, no treatment for a healthy individual. Infants are being evaluated using antiviral drug therapy G anciclovir is being used for patients with depressed immunity. Prevent ion - Blood components are not universally screened for CMV because of the generally benign course of this disease and the high percentage of virus carriers. To prevent CMV transmission, LD blood or blood from seronegative donors may be used.

18. Epstein-Barr Virus 95% of the adult population in the United States have been exposed to the virus by the age of 40 years Maintain an asymptomatic latent infection in B lymphocyte s for life. Infections occurring in infants or young children are usually asymptomatic. In adolescence and young adulthood, EBV causes infectious mononucleosis R eactivation usually occurs only in immunocompromised individuals Transmission- EBV has been called the “kissing disease” because the virus usually replicates in the cells of the oropharynx, possibly in infected B cells . The virus is shed in the saliva and is most frequently associated with infectious mononucleosis.

19. Parvovirus B19 Causes a common childhood illness called “fifth disease” Transmission - respiratory secretions. Pathogenesis- B19 parvovirus enters RBC s via the P antigen and replicates in the erythroid progenitor cells . The cytotoxicity of erythroid precursors can lead to serious illness in individuals with chronic hemolytic anemia, such as sickle cell disease and thalassemia Hydrops fetalis and fetal death can occur when the virus is transmitted during pregnancy. The viremic stage occurs shortly after infection. A donor would be asymptomatic but capable of transmitting the virus during this period

20. Parvovirus B19 Symptoms- Fifth disease presents with a mild rash described as “ slapped cheek ” when occurring on the face and a lacy red rash when occurring on the trunk and limbs Current trends- B19 has been implicated in several recent studies, with transmission through factor concentrates, mainly an antithrombin III concentrate H as led some manufacturers and regulatory authorities to require B19 DNA qualification testing of plasma

21. Emerging Bacterial pathogens

22. Bacteria PREVELANCE- According to the CDC, Yersinia enterocolitica is the most common isolate found in RBC units, followed by the Pseudomonas species. These two account for more than 80% of all bacterial infections transmitted by RBCs. Staphylococcus epidermidis or Staphylococcus aureus- most common bacterial contaminants of blood. Propionibacterium acnes , a common isolate of human skin, was the most common bacterial contaminant in RBCs. Slow growing anaerobic bacteria that can go unrecognized if tested in aerobic conditions or by using short-term bacterial cultural methods.

23. Because the bacteria in the unit consume the oxygen, the cells may lyse, resulting in discoloration in the unit as compared with the segments that remain normal in color . It is better to test the component itself and not the segments, as they may be negative CURRENT TRENDS- Bacterial screening of platelets was implemented in the United States from 2003 to 2004 The FDA has approved a psoralen/UV irradiation–based pathogen reduction method for use on apheresis platelets. The 31st edition of the AABB Standards states that “the blood bank or transfusion service shall have methods to detect bacteria or use pathogen reduction technology in all platelet components

24. PREVENTION- Phlebotomy diversion consists of collecting the first 20 to 30 mL of blood in a separate container Water baths used in a blood bank can have high bacterial counts unless disinfected frequently TREATMENT- IV antibiotics and symptomatic management

25. Emergent Parasites

26. Transfusion-Associated Parasites Most common- Babesia microti , Trypanosoma cruzi , and malaria ( Plasmodium species). Several additional parasites have been identified in association with transfusion associated Disease including Leishmania species, other Trypanosoma species, Toxoplasma gondii, and the microfilarial parasites. I nvolve patients who are severely immunocompromised Donor criteria- October 2003, the AABB put forth a recommendation to blood collection facilities that all individuals who had been in Iraq should be deferred for 1 year from the last date of departure. This was done after cases of leishmaniasis were reported in personnel stationed in Iraq.

27. Babesia microti Babesiosis , a zoonotic disease, is usually transmitted by the bite of an infected deer tick. Babesia infects the RBCs , so, infection may also be acquired by blood transfusion and solid organ transplant. Symptoms- usually develop a malaria-type illness characterized by fever, chills, lethargy, and hemolytic anemia. I ncubation period- 1 to 8 weeks after transfusion

28. Babesia microti DONATION CRITERIA- B. microti can survive in refrigerated, uncoagulated blood for 21 to 35 days . Infected persons who donate blood during the asymptomatic period pose the greatest risk to the blood supply Currently there is no licensed screening test for blood donors. IND protocols for antibody and DNA testing are being used by several blood centers. TREATMENT- no specific drug of choice, but quinine and clindamycin are very effective atovaquone and azithromycin can be as effective in patients without a life-threatening illness

29. T. cruzi (Chagas Disease) The i nfection is generally mild, but it persists, without symptoms, throughout the infected individual’s life and can be transmitted through blood transfusions. Symptoms- anemia, weakness, chills, intermittent fever, edema , lymphadenopathy, myocarditis, and gastrointestinal symptoms. Death may occur within a few weeks or months after initial infection. Blood transmission- Following the acute phase, the disease may enter a latent phase, which can last up to 40 years. During this phase, the patient is usually asymptomatic but has parasites circulating in the bloodstream.

30. Chagas disease Transmission- congenitally, transplacentally , or through solid organ transplantation In 2007, some donor centers began testing, and in 2010 the FDA released their final recommendations for donor screening by ELISA Donor criteria- Repeat reactive donors must be deferred indefinitely and the products quarantined and destroyed. Diagnosis- No approved confirmatory tests are available.

31. Emergent Prions

32. Creutzfeldt-Jakob Disease one of the transmissible spongiform encephalopathies Blood transmission- Prion particles have been found in lymphoreticular tissues , including the tonsils, spleen, and lymph nodes. As blood is intimately involved with the lymphoreticular system, concerns arose regarding the ability of vCJD individuals to transmit the prion to recipients of blood or blood products Currently, there is no reliable diagnostic test that can detect asymptomatic individuals. Therefore, donors are deferred indefinitely.

33. Relevance of emergent pathogens in Transfusion practice Examples are Human B19 parvovirus (B19V), which selectively infects erythrocyte progenitor cells, leading to red cell aplasia, aplastic crisis or even generalized pancytopenia in patients with immune compromise or with diseases that result in increased erythropoiesis. Some viruses, including the haemorrhagic fever viruses and dengue virus may cause bleeding disorders, capillary leakage or platelet deficiencies. P arasites such as  Babesia  and  Plasmodium  spp. can lead to haemolytic disorders.

34. Guidelines in India

35. Conclusion The risks of collecting a viraemic blood donation have been calculated for specific outbreaks such as of CHIKV, DENV and WNV. Those responsible for the safety of the blood supply are uneasy with the increasing burden of testing and point out that this incremental approach to the maintenance of safety is neither sustainable nor economically realistic . Many hope for a generic solution to the problem in the form of an effective and accessible pathogen reduction technology for all blood components, but it is unclear whether such an approach can stand alone, or whether it can only supplement other interventions.

36. References DGHS. Tranfusion Medicine Technical Manual 3 rd edition AABB Technical manual 18 th edition Harmening DM. Modern Blood Banking & Transfusion Practices 7 th edition Dodd R. Y. (2012). Emerging pathogens and their implications for the blood supply and transfusion transmitted infections.  British journal of haematology ,  159 (2), 135–142. https://doi.org/10.1111/bjh.12031 THANKYOU