Interim Guidelines on Investigating Deaths related to Dengvaxia Immunization

February 28, 2018

DOH ADMINISTRATIVE ORDER NO. 2018-0007

 

I. RATIONALE

From 2016 to 2017, the Department of Health (DOH) piloted the implementation of the Dengvaxia Vaccine in areas where there were high prevalence of Dengue, specifically in the provinces of Region III, Region IV-A, National Capital Region (NCR) and Region VII. The said vaccines were administered to students, aged nine (9) years old and above. Consequently, there were children who reportedly died of Dengue after being vaccinated with Dengvaxia.

In December 2017, DOH created a Technical Committee, the Dengue Task Force, to attend to technical and operational concerns after it was reported that the vaccine could lead to severe infection for those who have not had previous Dengue infection.

Subsequently, the DOH partnered with the University of the Philippines-Philippine General Hospital (UP-PGH) to validate deaths related to Dengvaxia, in which a Dengue Investigative Task Force (DITF) was created, consisting of independent body of expert physicians from the Philippine General Hospital, tasked to evaluate the cause of deaths associated with Dengvaxia.

The Presidential Decree No. 856, otherwise known as the "Code on Sanitation of the Philippines" authorizes the Secretary of Health to promulgate rules and regulations in the implementation of the said Code, where Section 95 of the same law provides for the conditions and requirements in the conduct of autopsies. Correspondingly, in March 2013, a User Manual on "Causality Assessment of an Adverse Event Following Immunization" was issued by the World Health Organization (WHO) as a guide to a systematic, standardized global causality assessment process for serious adverse events following immunization (AEFI).

With the current gaps in scientific evidence regarding Dengvaxia and its effects to the targeted population, the formulation of an interim policy is warranted to formalize the process of investigating the deaths for scientific purposes, and allowing autopsy to substantiate conclusions from documentary analysis of deaths.

II. OBJECTIVE

To institute standard operating procedures in the conduct of autopsy and in the investigation of cases of deaths associated with Dengvaxia vaccines.

III. SCOPE

This Administrative Order applies to:

1. The documentary analysis of deaths related to Dengvaxia immunization by the DITF.

2. Autopsies to be performed in all public and private hospitals and other health facilities for deaths among Dengvaxia vaccinees.

IV. DEFINITION OF TERMS

1. Anatomic pathologist — is a medical specialist board-certified in anatomic pathology concerned with the diagnosis of disease through the examination of specimens derived from autopsy and surgical procedures. The specimen can be in the form of an organ or, tissue assessed by gross and microscopic analysis and complemented by biochemical, immunohistochemical and molecular tests.

2. Autopsy — an examination of a body after death to determine the cause of death or the character and extent of changes produced by disease. This includes the external and internal examination of the body and its organs and supplemented by microscopic examination when necessary.

3. Causal Association — an agent is said to have a causal association with a particular disease when it can be shown that it plays some role in producing the occurrence of the disease.

4. Complete Autopsy — autopsy of the thoracoabdominal region and the brain.

5. Dengue Investigative Task Force (DITF) — served as the independent body of expert physicians from the University of the Philippines-Philippine General Hospital (UP-PGH) to evaluate deaths among Dengvaxia vaccinees.

6. Exhumation — the removal or disinterment of remains from places of interment.

7. Forensic Pathologist — is a pathologist with subspecialty training in forensic pathology who specializes in the legal aspects of pathology using scientific and medical technology to determine the cause of death.

8. Limited Autopsy — includes post-mortem examination of certain/specific organs of the body.

9. Local Health Authority — an official or employee responsible for the application of a prescribed health measure in a local political subdivision.

10. Local Health Officer — the provincial, city or municipal health officer.

11. Partial Autopsy — autopsy limited to the thoracoabdominal region.

V. GENERAL GUIDELINES

1. All cases of deaths among Dengvaxia vaccinees must be reported based on Administrative Order No. 2018-004 entitled, "Interim Guidelines on the Surveillance of Adverse Events among Dengvaxia Vaccinees (AEDV Surveillance)"

2. All medical documents of Dengvaxia-related deaths shall be submitted to UP-PGH DITF within 24 hours after death, for assessment of causality.

3. All Dengvaxia related deaths shall be advised for autopsy, including those who have already been buried, provided the required consent of the next of kin of the deceased, and the local health officer were obtained, accordingly.

VI. SPECIFIC GUIDELINES

1. Submission of Clinical Records to UP-PGH DITF

All public and private hospitals are required to submit within 24 hours to UP-PGH DITF the complete clinical records of the deaths related to Dengvaxia vaccines, for assessment.

2. Consent before the Conduct of Autopsy

a. All deaths associated with Dengvaxia will be advised to undergo autopsy, provided that consent shall be secured from the next of kin. The order of priority for obtaining consent from the next of kin of the deceased child vaccinated with Dengvaxia, viz.:

i. Parents

ii. Siblings (18 years old and older)

iii. Grandparents

iv. Guardian (at time of death)

b. For those unwilling to give consent to a complete autopsy, a consent for partial or limited autopsy shall be secured from the next of kin.

c. For those completely unwilling to give consent to autopsy, the clinical records of the Dengvaxia related deaths shall be submitted to UP-PGH DITF for assessment of causality. As soon as causal association with Dengvaxia is established, an exhumation of the body of the deceased shall be undertaken for further review/study, provided that consent from the next of kin shall be obtained and a disinterment or exhumation permit shall be issued by the local health officer in accordance with the requirements specified hereof.

d. In case the deceased has no next of kin, permission from the local health officer shall be secured.

3. Institutions/Persons Authorized to Perform Autopsy:

a. DOH shall designate select DOH Level 3 Hospital in Regions III, IV-A, VII and NCR or DOH Reference Hospitals for Autopsy of Dengvaxia-related deaths. (Annex A)

b. DOH shall assign UP-PGH as the "APEX" Hospital, responsible for the following to establish causality thru the UP-PGH DITF:

i. Documentary Review of all clinical records of Dengvaxia-related deaths;

ii. Receipt and Analysis of all Autopsy Findings of deaths related to Dengvaxia from DOH-Reference Hospitals;

iii. Correlation of Documentary Review and Autopsy Findings to establish causality or non-causality of deaths to Dengvaxia Vaccines;

iv. Endorse to DOH all reports for the investigation;

v. Settle all disputes related to the conduct of investigation among Dengvaxia-related deaths;

vi. Maintain utmost confidentiality in the performance of their function; and

vii. Endorse to DOH all request for reports or interview.

c. All certified Anatomic Pathologists in DOH Reference Hospital for autopsy shall be authorized to perform autopsy of the remains of Dengvaxia vaccinees, using the standard procedures in autopsy, provided they have undergone orientation on uniform implementation of autopsy conducted by the UP-PGH DITF.

d. For deaths occurring in hospitals not identified as DOH Reference Hospitals or deaths in private hospitals, the designated Autopsy Team shall conduct the autopsy in the nearest government hospital, or in the National Bureau of Investigation (NBI) — accredited morgue (Annex B), within the locality.

e. The Autopsy Team shall be composed of the following from the DOH Reference Hospital:

i. One (1) Anatomical Pathologist

ii. Two (2) Mortician trained in evisceration

 DOH may invite a foreign pathology expert as resource person in the Autopsy Team, if deemed necessary.

4. Personnel Permitted at Autopsy

The pathologist is responsible for deciding who can be present during the autopsy. The next of kin shall be informed of their right to have a physician of their choice to be present as observer during the performance of the autopsy.

To ensure the proper documentation and for transparency, list of attendees and assistants shall be maintained as witnesses during the conduct of autopsy.

5. Analysis of remains should be based on but not limited to the following information:

a. History of Dengvaxia immunization

b. Medical records

c. Specific sample or specimen to be collected

d. Necessary laboratory tests to be conducted

6. Requirements for autopsies of patients:

a. The director or medical chief of the hospital shall notify in writing the next of kin of the deceased and request permission to perform autopsy.

b. Autopsy can be performed when the permission is granted or no objection is raised to such autopsy within 48 hours after death.

c. In cases where the deceased has no next of kin, the permission shall be secured from the local health authority.

Before the autopsy is started, the autopsy permit (authorization) must be reviewed carefully ensuring that the name of the decedent specified therein matches the identification of the body that is subjected to autopsy. It is also essential to note in the autopsy permit the limitations, if any, that the next of kin wishes to undertake in the autopsy procedure. (Annex C)

7. All pathologic examinations of tissues obtained from autopsy shall be done in all DOH reference hospitals, results of which and other autopsy findings shall be submitted to DITF for correlation with documentary review of clinical records.

8. Requirements for Exhumation

a. The disinterment or exhumation permit shall be issued by the local health officer and all disinterment of remains shall be under his supervision.

i. Exhumation of bodies or remains of persons of Dengvaxia vaccinees may be granted within three (3) days from the approval of the DOH-Regional Director concerned;

ii. The remains upon exhumation shall be properly identified as to the name of the deceased, date and cause of death and place of origin;

iii. Exhumation and transfer permits shall be secured from the point of origin;

iv. Death certificate shall be obtained, for reference; and

v. Reburial permit shall be secured at the place of reinterment.

9. Risk Communication to Bereaved Family

a. Interventions should be made that involve strengthening the bereaved family's coping mechanisms and establishing a caring presence and using effective communication strategies to encourage them to comfortably share their feelings.

b. After ascertaining stability of the family of the deceased, the family should be reassured that a properly standard autopsy will be performed to determine and confirm the cause of death of the deceased and the possible connection to Dengvaxia, which could likewise be used for either documentation purposes or presentation of evidence in judicial investigation or both, as the case may be.

c. Any proprietary or confidential information obtained during the autopsy shall not be disclosed without prior consent or clearance from DOH.

10. Referral Facilities Authorized to Conduct Autopsy

a. All DOH Reference Hospitals in Regions III, IV-A, NCR and VII will conduct autopsy.

b. If patient died in a lower level facility or at home, the autopsy may be conducted by the autopsy team in a NBI-accredited morgue.

11. Securing Records and Evidence

a. The following information of the deceased patient may be secured from the health facility, after consents are obtained from the attending physician and the next of kin:

i. Clinical abstract

ii. Laboratory result

iii. Doctor's order

iv. Discharge summary

b. Without court order, release of information shall be pursuant to hospital policy otherwise, patient records shall not be released or disclosed.

c. The Anatomic Pathologists and the Autopsy Team shall preserve all evidence that they accumulate in the course of the autopsy that confirms the cause of death of the deceased. Their findings shall be submitted to UP PGH DITF for further assessment.

d. Evidence of cause of death of the deceased acquired in the performance of autopsy as certified by the UP-PGH DITF shall be endorsed to the DOH for decision-making and if warranted, endorsed to the appropriate law enforcement agency.

VII. FUNDING

1. Expenses relating to the investigation of deaths among Dengvaxia vaccinees shall be chargeable against the DOH — Disease Prevention and Control Bureau (DPCB) funds.

2. Specifically, all expenses related to the process of conducting Autopsy of deaths among Dengvaxia Vaccinees shall be charged against the specific DOH Reference Hospital.

3. The OSEC-DOH shall transfer P500,000.00 for each DOH Reference Hospital as initial funding for the conduct of autopsy.

4. All expenses are subject to the usual accounting and auditing rules and regulations.

VIII. SEPARABILITY CLAUSE

If any section or part of these Operational Guidelines is held invalid or unconstitutional, the remainder not otherwise affected shall remain valid and subsisting.

IX. EFFECTIVITY

This Order shall take effect fifteen (15) days after its approval and publication in a newspaper of general circulation.

(SGD.) FRANCISCO T. DUQUE III, MD, MSc

Secretary of Health

ANNEX A

DOH Reference Hospitals

Name

Location

Region III

1. Dr. Paulino J. Garcia Memorial Research and Medical Center	Cabanatuan City, Nueva Ecija
2. Jose B. Lingad Memorial Regional Hospital	San Fernando, Pampanga

Region IV-A

1. Batangas Medical Center

Kumintang Ibaba, Batangas

NCR

1. East Avenue Medical Center	East Ave., Diliman, Quezon City
2. Jose R. Reyes Memorial Medical Center	Sta. Cruz, Manila
3. National Kidney and Transplant Institute	East Ave., Diliman, Quezon City
4. Philippine Children's Medical Center	Diliman, Quezon City
5. Philippine Heart Center	Diliman, Quezon City
6. Quirino Memorial Medical Center	Project 4, Quezon City
7. Rizal Medical Center	Pasig Blvd., Pasig City
8. Tondo Medical Center	Lopez Blvd., Tondo, Manila

Region VII

1. Governor Celestino Gallares Memorial Hospital	Tagbilaran City, Bohol
2. Vicente Sotto Memorial Medical Center	Cebu City, Cebu

ANNEX B

NBI-Accredited Morgue

Name

Location

Region III

1. St. Louise Funeral Parlor	Porac
2. St. Louise Funeral Parlor	Lubao
3. St. Louise Funeral Parlor	San Fernando
4. Enriquez Funeral Homes	Tarlac City
5. Angelinos Memorial Chapels	Angeles City

Region IV-A (None)

NCR

1. Almo Funeral and Mortuary Services	Phase 4, Package 4, Powerline Bagong Silang, Caloocan City
2. Amore Funeral Homes	Block 5, Lot 12, MRT Avenue, Central Signal Village, Taguig City
3. Arlington Memorial Chapels, Inc.	12 G. Araneta Avenue, Quezon City
4. Atienza Funeral Services Corp.	296 Ligas II, Bacoor City, Cavite
5. C.G. Flores Funeral Home, Inc.	219 Gen. Luna St. Brgy. Conception, Malabon City
6. Dayao Funeral Home	2 & 4 Bayani St. Galas, Quezon City
7. Dulce Memorial Service	Jose Abad Santos Avenue, Manuguit, Manila
8. Eastern Funeral Services	423 East Service Road Alabang, Muntinlupa
9. Eliseum Memorial Chapels	2994 Maliklik Cor. Juan Luna St. Gagalangin, Tondo Manila
10. Floresco Funeral Homes	511 A. Mabini St. Caloocan City
11. Funeraria Cruz	2620 Severino Reyes St. Sta. Cruz Manila
12. Funeraria Filipinas, Inc.	187 Real St. Pamplona 1 Las Piñas City
13. Funeraria Filipinas, Inc.	865 J.P Rizal Ave., Makati City
14. Funeraria L.A. Vasquez	6 Real St. Manuyo 1, Las Piñas City
15. Funeraria Malaya	159 Libertad St. Pasay, Metro Manila
16. Funeraria Mesina	Blk 2, Lot 11, Greenvalley, Molino III, Bacoor City, Cavite
17. Guevara Funeral Home	5967 Tramo St. San Dionisio, Parañaque City
18. Holy Trinity Memorial Chapels and Crematorium	Dr. A. Santos Ave. Parañaque City
19. Ilagan Memorial Homes	2364 Onyx St. San Andres Bukid, Manila
20. King Harold Memorial and Funeral Services	15 National Road Alabang, Muntinlupa City
21. La Bien Memorial Chapel, Inc.	9003 Gen. Evangelista St. Maliksi II, Bacoor, Cavite
22. La Funeraria Paz-Sucat, Inc.	Manila Memorial Park, Dr. A. Santos Ave., Parañaque City
23. La Funeraria Real	1 M.L. Quezon St. Bambang, Taguig City
24. La Funeraria Rey	2385 Laura St. Pandacan, Manila
25. LG Flores Memorial Chapels	1569 Pedro Gil St. Paco, Manila
26. Maven Funeral Homes	200 Commonwealth Ave. Brgy., Commonwealth, Fairvew, Quezon City
27. Nateh Funeral Homes, Inc.	1194 M. Naval St. Daang Hari, Navotas City
28. Norsam Memorial Chapels	170 Tandang Sora Ave., Banlat, Quezon City
29. People Funeral Service, Inc.	Blk 2, Lot 12, Rafael St. San Antonio Valley, Pulang Lupa 2, Las Piñas City
30. Prestige Memorial Chapels	Block 1, Lot 21, J.P. Rizal Street Concepcion 1, Marikina City
31. Roca Funeral Homes	145 Quirino Ave., Baclaran, Parañaque
32. Royalty Funeral Homes	Unit 8, Mikesell Compound Marcos Alvarez Ave., Talon 5, Las Piñas City
33. San Fernando Funeral Homes and Crematory	167 Kaingin Road, Balintawak, Quezon City
34. St. Mark Memorial Chapel	1615 G. Tuazon Corner Loreto St. Sampaloc, Manila
35. St. Mary Magdalene Funeral Home	59 Ilaya St. Niog III, Bacoor City, Cavite
36. St. Peter Memorial Chapels	296 Quezon Ave., Quezon City
37. Yeyo Sabino Funeral Service	Norma Sabino Compound, Maysan, Valenzuela City

Region VII

1. Cosmopolitan Funeral Parlor

Cebu City

As of January 2018

ANNEX C

Summary of Specimen Collection, Storage, and Transport from A.O No. 2018-0006

Sample Type

Timing of Collection

Quantity

Storage prior to transport

Transport

For vaccine recipients who are admitted and ill:

Serum

Upon first contact with patient

3 ml

Refrigerator, 2 to 8°C

• Transport within 48 hours or 2 days after collection • Use the prescribed transport box with gel or ice packs

For vaccine recipients with severe Dengue:

Serum-Acute Phase	Less than 5 days after onset of fever (< 5 days) or upon first contact with the patient	3 ml	Refrigerator, 2 to 8°C	• Transport within 48 hours or 2 days after collection • Use theprescribed transport box with gel or ice packs
Serum-Convalescent Phase	More than 5 days from onset of fever (> 5 days) or upon discharge	3 ml	Refrigerator, 2 to 8°C	• Transport within 48 hours or 2 days after collection • Use the prescribed transport box with gel or ice packs
Whole Blood-using Heparin as anticoagulant (Green Top)	Upon first contact with the patient	12 ml	Room Temperature	• Transport within 12 hours upon collection • Use the prescribed transport box with 1 gel or ice pack

For vaccine recipients who died:

Formalin-fixed tissues (Embalmed remains):     Post-mortem tissues from all major organs should be submitted for evaluation. Specimens should include: a. Heart (right ventricle, septum, and left ventricle). b. CNS (cerebral cortex, thalamus, basal ganglia, midbrain, pons, medulla, cerebellum, and spinal cord). Representative sections from the ff: a. Right & left lungs b. Right & left kidneys c. Spleen d. Liver e. Bone marrow f. Lymph nodes g. Any other organ showing significant gross pathology. h. Effusion: pleural and pericardial fluids     For limited autopsy, liver should at least be included; collect multiple slabs of tissue.	Collect specimen, as soon as possible after death	At least three pieces from each organ, each measuring at least 5.0 x 5.0 x 1.0 cm     Additional samples from the larger organs like the liver, kidneys, lungs and brain would be helpful.     Place each specimen in a wide-mouthed container/jar, submerged in 10% NEUTRAL BUFFERED FORMALIN (Label should include: patient's name, specimen type, laterality, date and time collected)     At least 5 to 10 mL fixed in 95% Ethanol (1:1 ratio)	Room temperature	• Transport immediately in a well-sealed container. • Store and ship at room temperature. • Specimens should not be frozen.
Fresh tissues:   Post-mortem tissues from all major organs should be submitted for evaluation. Specimens should include: a. Heart (right ventricle, septum, and left ventricle) b. CNS (cerebral cortex, thalamus, basal ganglia, midbrain, pons, medulla, cerebellum, and spinal cord) Representative sections from the ff: a. right & left lung b. right & left kidney c. Spleen d. Liver e. Bone marrow f. Lymph nodes g. Any other organ showing significant gross pathology h. Effusion: pleural and pericardial fluids     For limited autopsy, liver should at least be included; collect multiple slabs of tissue.	Collect specimen FRESH, as soon as possible after death	At least three (3) pieces from each organ, each piece measuring at least 2.0 cm.     All specimens (including effusion fluid) should be collected aseptically. Use a separate sterile instrument for each collection site. Place each specimen in sterile wide-mouthed container/jar (Label should include patient's name, specimen type, laterality, date and time collected).     At least 5 to 10 ml without any fixative.	Frozen at — 20°C prior to shipping; If unavailable, store at the refrigerator, 2 to 8°C	• Transport immediately in a well-sealed container. • Use the prescribed transport box with gel or ice packs • Avoid repetitive freezing and thawing of specimens.