Dengue and Blood Donors

1. Local Perspective of Dengue &
Hospital Impressions of the
Risk of Transfusion
Transmission
Raul H. Morales-Borges, MD
Medical Director
Puerto Rico Region
Blood Services
American Red Cross

2. INTRODUCTION
• Dengue is an infection caused by an arthropod-borne virus,
in particularly, by four related RNA viruses of the genus
Flavivirus, dengue virus (DENV)-1,-2,-3, and-4.
• The mosquito Aedes aegypti is the principal vector.
• DENV’s are transmitted from person to person and humans
are the main amplifying host.
• The disease spectrum goes from a mild acute febrile illness
to an hemorrhagic fever and severe shock.
• In Puerto Rico, dengue was first recognized in 1915 and the
most recent island-wide outbreak occurred in 2010.
• DENV was identified as one of three high priority infectious
agents with actual or potential risk of transfusion
transmission in the United States or Canada by AABB’s
Transfusion Transmitted Diseases Committee. 2
9/10/2012
PETERR CJ: Infections Caused by Arthropod- and Rodent-Borne Viruses (Chapter 189): In AS Fauci et al (eds.): HARRISON’S Principles of Internal Medicine17th
Edition, McGraw Hill Medical. 2008.
KM Tomashek and HS Margolis: Dengue: a potential transfusion-transmitted disease. Transfusion, 51(8):1654-1660.; August 2011.

3. EPIDEMIOLOGY
• The areas at risk for DENV transmission are Mexico,
Central and South America, the Caribbean including
Puerto Rico and US Virgin Islands, and part of Africa
and Asia continents.
• It exist in USA in the southern areas as well as in the
Mexico border.
• An estimated 50 million cases occur annually, 40% of
the world’s population live in the areas where there is
risk of DENV transmission, and dengue was the
leading cause of febrile illness among 17,353 ill
travelers returning from the Caribbean, South
America, South Central Asia, and Southeast Asia.
3
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KM Tomashek and HS Margolis: Dengue: a potential transfusion-transmitted disease.
Transfusion, 51(8): 1654-1660; August 2011.

4. WEEKLY REPORT FROM DENGUE SURVEILLANCE OFFICE
CDC & DEPARTMENT OF HEALTH OF PUERTO RICO
• By September 9 of 2011, at week 33 there have been
145 presumed cases notified and they are below the
historic average number. There have been 2453 cases
in total so far for year 2011.
• 26 % were confirmed by laboratory.
• 20 % of the municipalities confirmed with an
extended geographic classification.
• Classified by types:
• 63% DENV-1
• 36% DENV-4
• 1% DENV-2
• 0% DENV-3 4
9/10/2012
Provided by Aidsa Rivera, MS – Epidemiologist/Surveillance Officer at CDC, NCEZID, DVBD,
Dengue Branch

5. 1000
900 Dengue Suspected Cases
Reported
800
in Puerto Rico
2007
700
600
2010 1998
is similar to
Cases
500
1998
400
2010
2005
300
2009
200
2008
100
0
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51
1998 2005 2007 2008 2009
Week 2010
Source: Dengue Surveillance Weekly Report
CDC Dengue Branch & Puerto Rico Department of Health

6. 1000
900 Dengue Suspected Cases
Reported
800
in Puerto Rico
2007
700
2011 1998
600
Cases
500
400
2010
2005
300
2009
200
2011
2008
100
0
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51
1998 2005 2007 2008 2009 Week 2010 2011
Source: Dengue Surveillance Weekly Report
CDC Dengue Branch & Puerto Rico Department of Health

7. CLINICAL PICTURE
• 53% to 87% of dengue infections are asymptomatic or mildly symptomatic.
• Dengue infection has a median 5-day viremia, and symptom occurs 1 day after
onset of viremia.
• After an incubation period of 2 – 7 days, the typical patient experiences the
sudden onset of fever, headache, retroorbital pain, and back pain along with the
severe myalgia that gave rise to the colloquial designation “break-bone-fever”.
• There is often a macular rash on the first day as well as adenopathy; palatal
vesicles, and scleral injection.
• The illness may last a week, with additional symptoms usually including anorexia,
nausea or vomiting, marked cutaneous hypersensitivity, and - near the time of
defervescence - a maculopapular rash beginning on the trunk and spreading to
the extremities and the face.
• Epistaxis and scattered petechiae are often noted in uncomplicated dengue.
• Laboratory findings includes:
• Leukopenia
• Thrombocytopenia
• Serum aminotransferase elevations
7
CJ PETERS: INFECTIONS CAUSED BY ARTHROPOD- AND RODENT-BORNE VIRUSES (CHAPTER 189).
In Harrisons Principles of Internal Medicine, 17th Ed., 2008. 9/10/2012
H Mohammed, JM Linnen, JL Munoz-Jordan, K Tomashek, G Foster, AS Broulik, L Petersen, SL Stramer: Dengue virus in blood donations,
Puerto Rico, 2005. Transfusion 48: 1348-1354, July 2008.

8. DIAGNOSIS OF THE DENGUE
• The diagnosis is made by IgM ELISA or paired serology
during recovery or by antigen-detection ELISA or Reverse
Transcription-PCR during the acute phase.
• Virus is readily isolated from blood in the acute phase if
mosquito inoculation or mosquito cell culture is used.
• Detection of DENV is possible using immunoassays that
detect soluble DENV nonstructural protein 1 (NS1) antigen,
which circulates during the course of the viremic phase of
the illness.
• DENV RNA can be detected in serum by a number of
nucleic acid amplification methods, including RT-PCR,
transcription-mediated amplifications (TMA), reverse
transcriptase loop-mediated isothermal amplification, and
nucleic acid sequence-based amplification, but they are not
commercially available yet.
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9. DENGUE IN BLOOD DONATIONS
• One study in PR by ARC from September to December 2005 using
TMA in all blood donors, they found that 12 (0.07%) of 16,521
blood donations tested were TMA-positive, furthermore, live
virus was recovered from three of the 12 TMA(+) donations,
indicating that at least 3 were capable of transmitting infection to
recipients.
• The prevalence of dengue viral nucleic acid in blood donations in
that study was similar to that estimated for WNV in the areas
experiencing outbreaks in the continental United States in 2002
before universal screening using minipool NAT was implemented
in July 2003.
• They recommended further evaluation to asses the risk of dengue
transmission by TMA(+) donations and the cost and benefit of
routine dengue screening in endemic regions.
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H Mohammed et al: Dengue virus in blood donations, Puerto Rico, 2005. Transfusion 48: 1348-1354, July 2008.

10. RECENT TRANSFUSION TRANSMISSION CASES IN PR
• > 92% of Blood components were RBC’s.
• > 92% of the cases were reactive.
• On 2010 all of the components involved were
distributed across the Island.
• On 2011, around one half were distributed out
in USA and the rest in PR.
• Most of the cases of the recipients did no
present symptoms.
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11. DENGUE & BLOOD INVENTORY IN PUERTO RICO
• We stopped exporting blood to USA on May 2009, reinitiated on
March 2010, then stopped by August 23, 2011.
• During the 2010 outbreak, hospitals increased significantly their
demand for platelet products as well as some RBC’s, but in less
proportion.
• This year 2011 we have seen more hemorrhagic manifestations
with thrombocytopenia, so, platelets usage has increased in the
past 2 months, but not at the rate we saw last year.
• No outbreak this year.
• We don’t need to reduce deliveries of orders received and we
can even deliver to non-contracted hospitals. Our collections are
significantly higher than our demand, so we have an excess of
over 1000 units per month which if we can not push them into 14
the local market, we will need to discard.
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12. ISSUES & QUESTIONS IN PR
• We noticed that the cases are lower than in previous years
and they are lower after the storm/hurricane season.
• We are concern about the false positive results with NS-1.
• Can we obtain a more sensitive test than NS-1?
• The Hospitals do not have an idea of how big is this problem
regarding transfusion transmission, but they are
collaborating so far.
• They don’t want to make this a big issue because they don’t
want to develop a risk management case (lawsuit?) from the
patients side.
• Many physicians are unaware of dengue transfusion
transmission.
• Are we responsible of giving them the appropriate education
about this issue?
• How we can get them involved in prevention of transfusion
transmission?

13. MANAGEMENT STRATEGY FOR PUERTO RICO DURING A
DENGUE OUTBREAK
• Assess the risk of dengue transmission by TMA-positive donations &
NS-1 (+) as well as the cost-effectiveness of routine dengue screening.
Look for more sensitive test.
• Evaluate the weather seasons in Puerto Rico and the correlation with the
prevalence and transmission rate to determine when is better to do
blood drives in the Island.
• Defer at-risk donors, e.g. symptoms of fever, travel history to endemic
regions, exposure to dengue patients, etc.
• Continue with the Dengue Follow-Up Study. Track & Receive Plasma
Units associated with Reactive Samples for Confirmatory Testing.
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14. CONCLUSIONS AND RECOMMENDATIONS
• Transfusiontransmission of DENV has
been demonstrated. We need to educate
more the health professionals (e.g.. Nurses,
Physicians).
• There are few options for minimizing
dengue risk in the blood supply, but we still
need more studies in testing and
prevention.
• Guidelines for these cases needs to be
established.
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15. Acknowledgements
• Antonio de Vera, Executive Director, ARC of PR, Blood
Services
• Carmen Merced, Manager, Donor Information, ARC of PR,
Blood Services.
• Aidsa Rivera, MS, Epidemiologist/Surveillance Officer, CDC,
Health Department of PR.

16. Acknowledgements
• Antonio de Vera, Executive Director, ARC of PR, Blood
Services
• Carmen Merced, Manager, Donor Information, ARC of PR,
Blood Services.
• Aidsa Rivera, MS, Epidemiologist/Surveillance Officer, CDC,
Health Department of PR.