Local Perspective of Dengue & Hospital Impressions of the

Risk of Transfusion Transmission

Raul H. Morales-Borges, MDMedical Director

Puerto Rico RegionBlood Services

American Red Cross

• 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.

INTRODUCTION

PETERR CJ: Infections Caused by Arthropod- and Rodent-Borne Viruses (Chapter 189): In AS Fauci et al (eds.): HARRISON’S Principles of Internal Medicine17 th Edition, McGraw Hill Medical. 2008.KM Tomashek and HS Margolis: Dengue: a potential transfusion-transmitted disease. Transfusion, 51(8):1654-1660.; August 2011.

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• 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.

EPIDEMIOLOGY

KM Tomashek and HS Margolis: Dengue: a potential transfusion-transmitted disease. Transfusion, 51(8): 1654-1660; August 2011.

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• 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

WEEKLY REPORT FROM DENGUE SURVEILLANCE OFFICECDC & DEPARTMENT OF HEALTH OF PUERTO RICO

Provided by Aidsa Rivera, MS – Epidemiologist/Surveillance Officer at CDC, NCEZID, DVBD, Dengue Branch

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Source: Dengue Surveillance Weekly ReportCDC Dengue Branch & Puerto Rico Department of Health

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Dengue Suspected Cases Reported

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Source: Dengue Surveillance Weekly ReportCDC Dengue Branch & Puerto Rico Department of Health

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2011

• 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

CLINICAL PICTURE

CJ PETERS: INFECTIONS CAUSED BY ARTHROPOD- AND RODENT-BORNE VIRUSES (CHAPTER 189). In Harrisons Principles of Internal Medicine, 17th Ed., 2008.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.

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• 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.

DIAGNOSIS OF THE DENGUE

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• 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.

H Mohammed et al: Dengue virus in blood donations, Puerto Rico, 2005. Transfusion 48: 1348-1354, July 2008.

DENGUE IN BLOOD DONATIONS

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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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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 the local market, we will need to discard.

• 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?

ISSUES & QUESTIONS IN PR

MANAGEMENT STRATEGY FOR PUERTO RICO DURING A DENGUE OUTBREAK

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• 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.

CONCLUSIONS AND RECOMMENDATIONS

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• Transfusion transmission 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.

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.

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.