RITM Responds to MERS-CoV Threat in the Country

RITM is now ISO 9001:2008 certified

An imported case of MERS-CoV in the country proved RITM’s

preparedness for emerging infectious disease threats.

As the Department of Health’s (DOH) National Referral Center for Emerging and Reemerging Infectious Diseases, the Research Institute for Tropical Medicine (RITM) responds to the threat of the Middle East Respiratory Syndrome-Corona Virus (MERS-CoV) in the Philippines. On April 15 , 2014, the arrival of a 45-year-old male Filipino nurse who initially tested positive for the MERS-CoV in the United Arab Emirates (UAE) put RITM’s response to test.

RITM immediately activated its Emergency Operations Center (EOC) and ensured effi cient hospital containment of suspected cases and rapid laboratory response. RITM performed rapid testing of samples obtained from passengers of the Etihad fl ight EY 0424,

The Research Institute for Tropical Medicine (RITM) received its

International Organization for Standardization certifi cate on Quality Management System (ISO 9001:2008) after undergoing a rigid application process. RITM obtained the certifi cate on July 11.

RITM is now an ISO certifi ed institution for the provision of Administrative, Medical, and Research and Development Services, including Knowledge and Technology Transfer.

RITM met the criteria of an organization with quality management system including policies such as strong customer focus, top management support, organizational process strategy, and continual improvement. Furthermore, RITM successfully complied with and showed evidence for documentation and implementation of mandatory ISO 9001:2008 requirements: control of documents, control of records, internal audit, control of nonconforming product, corrective action, and preventive action.

The fi rst stage of the audit was conducted on February 7. It was followed by the second stage audit on April 11, before certifi cation was granted.

RITM adopted ISO 9001:2008 standards in compliance with the Executive Order No. 605 which directs all government departments and agencies to institutionalize Quality Management Systems as part of a government-wide quality management program.

the plane which carried the male Filipino nurse. Among the 414 passengers of EY 0424, 410 were tracked and tested for MERS-CoV including the male Filipino nurse who initially tested positive in UAE. All of them tested negative for the infectious disease.

“We immediately coordinated the results to the DOH Central Offi ce, National Epidemiological Center and Regional Epidemiology and Surveillance Units as soon as the laboratory tests were released,” explained Rowena Capistrano of the RITM Surveillance Unit.

Meanwhile, all of the four remaining passengers who were not traced had already left the country when the surveillance for the MERS-CoV was activated.

>RITM Celebrates 33rd Anniversary

p6

>RITM Labs Receive WHO Accreditation

p2

>Message from the RITM Director

p2

>Feature: In the Time of Dengue Mitigation

p4

>Infographic: RITM’s Response to MERS-CoV

p3

>Staff Updates

p8

>> continued on page 2

WHAT’S INSIDE >>

An RITM molecular biologist performs MERS-CoV molecular testing of samples from the Etihad fl ight EY0 424’s passengers.

2 RITM UPDATE APRIL-JUNE 2014

RITM has updated rapid detection methods, well-equipped laboratory and hospital facilities, and trained personnel in responding to the threat of new infectious disease agents. RITM currently uses molecular detection methods which ensure sensitive and rapid diagnosis. RITM can also detect the virus by electron microscopy and histopathology. RITM is also part of a global network of laboratories which provide mutual support for confi rmation and further characterization of new infectious agents.

“The laboratory procedures that RITM follows are recommended by the World Health Organization,” added Edelwisa Mercado, Head of the RITM Molecular Biology Laboratory.

Three national reference laboratories of RITM, namely the National Polio Laboratory, the National Measles Laboratory, and the National Japanese Encephalitis Laboratory, all under the Department of Virology, were accredited by the World Health Organization (WHO) in terms of their capability and capacity to detect, identify, and promptly report target pathogens.

As part of the WHO Laboratory Network for Polio, Measles and Japanese Encephalitis, the laboratories’ performance is evaluated annually through several mechanisms: confi rmatory testing, profi ciency testing and site visit. Accreditation confi rms that the laboratories’ operations and procedures met the WHO standards.

“Confi rmatory testing is done by regularly sending clinical samples from the national reference laboratory (NRL) to the

RITM Responds...(from page 1) MESSAGE

From the RITM Director

Dear RITM Colleagues and Partners,

We are very happy that the fi rst issue of RITM Update is out. This quarterly newsletter will serve to inform RITM staff and partners on the Institute’s continuing contribution to the prevention and control of infectious and tropical diseases in the Philippines.

For the maiden issue, we are announcing that RITM is now ISO certifi ed. We are also featuring RITM’s signifi cant research and surveillance activities, including clinical studies on dengue vaccine in the country where RITM researchers are at the forefront. We are also sharing how the Institute responded effi ciently to the threat of the Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) in the Philippines.

We look forward for RITM Update as a means for RITM to stay connected as a community and to engage externally with our partners. We are also coming up with an annual report so this newsletter will serve as a preview.

With warm regards,

Socorro P. Lupisan, MDDirector IV, RITM

Mercado also stated that the patient who initially tested positive at UAE tested negative at RITM, denoting that the virus probably has been cleared while the patient was recovering on his way home.

The threat of emerging infectious diseases like MERS-CoV is no longer new to RITM. In the past, RITM has successfully responded to global public health emergencies such as the Severe Acute Respiratory Syndrome (SARS) in 2003, the Pandemic Infl uenza H1N1 (Swine Flu), and Ebola-Reston Vrus Infection in 2009.

RITM continues to receive specimens referred for testing by the National Epidemiology Center and by other institutions. To date, there has been no new recorded MERS-CoV case in the country.

RITM Labs Receive WHO Accreditation

designated regional reference laboratory for re-testing. The regional reference laboratory sends the result of their re-testing to NRL. Concordance with the results of the regional reference laboratory is monitored,” explained Dr. Amado Tandoc, head of the Department of Virology .

In profi ciency testing, the regional reference laboratory sends pre-tested panels to NRL for testing. The results of the regional reference laboratory is not revealed to NRL until after the latter has sent results from its own testing.

Finally, WHO sends laboratory experts to NRL for site visits at least once a year to review the performance for the preceding 12 months. Using a comprehensive checklist –from laboratory requirements

With warm regards,

Socorro P. Lupisan, MDDirector IV, RITM

A laboratory technician from RITM’s National Measles Laboratory performs measles IgM enzyme immunoassay.

>> continued on page 8

RITM UPDATE APRIL-JUNE 2014 3

4 RITM UPDATE APRIL-JUNE 2014

In the Time of Dengue MitigationRITM’s Contributions to the World’s Fight against the Disease

Nelia Dinulos, 51, is a mother of one. A few years ago, she encountered her biggest

challenge as a parent. Her nine-year-old daughter developed dengue.

At fi rst, Nelia thought it was just an ordinary fever. The fever though, would go on and off for a week. She fi nally decided to bring her daughter to the hospital. Laboratory tests confi rmed that her daughter was suff ering from dengue fever. Fortunately, the disease was detected early and proper medical attention led to her daughter’s recovery.

Dinulos shares this nightmare with the rest of 500, 000 parents every year - parents of children hospitalized because of serious cases of dengue. The World Health Organization (WHO) further accounts that around 50 to 100 million people are affl icted by dengue annually, and over 2.5 billion people (over 40% of the world’s population) are at risk to be infected. This makes dengue the world’s fastest-spreading mosquito-borne disease. Of those affl icted by the disease, 22,000 die.

Considered by WHO as a ‘neglected disease’, dengue is primarily transmitted to humans by two mosquito species—Aedes aegypti and Aedes albopictus. The virus can be transferred through the bites of infected female mosquitoes. Also, a dengue-affl icted human can indirectly

transmit the virus to other persons through the vector mosquitos. Studies suggest that female Aedes aegypti mosquitoes, the most common dengue vector in the world, tend to permanently stay in or around the houses where they emerge as adults. This may imply that people’s mobility could be more responsible in spreading the virus rather than the mosquitos.

A lot of preventive actions and control measures are being implemented to avoid the massive burden of the disease. These include early warning systems; vector control; environmental, epidemiological and disease surveillance; laboratory support; clinical case management; environmental controls; and social mobilization. Experts, however, fi rmly

believe that the availability of an eff ective vaccine is still ‘the holy grail’ of dengue prevention.

CYD-TDV Clinical Trial’s Promising ResultIn the Philippines, the clinical development of the world’s fi rst dengue vaccine to complete the initial Phase III effi cacy trial is conducted by the Research Institute for Tropical Medicine, with Dr. Rosario Capeding as the principal investigator. This potential vaccine is a live-attenuated tetravalent vaccine developed by the French pharmaceutical company Sanofi Pasteur (CYD-TDV).

The clinical trial included 10,275 children aged 2 to 14 in Indonesia, Malaysia, the Philippines, Thailand, and Vietnam. CYD-TDV yielded a promising result as it showed a signifi cant reduction of 56.5% of dengue disease cases in the fi ve countries combined.

A total of 3,500 children from the Philippines (with San Pablo City, Laguna and Cebu City as study sites) participated in the said clinical study of CYD-TDV. This makes the Philippines the country in Southeast Asian leg of the study with the highest number of enrollees. Capeding added that the Philippines, through RITM, is the only country which has been actively involved in all three phases of clinical development of CYD-TDV.

Asked what will be the implication of the study’s promising results, Capeding stated that it will have a big impact even if the Phase III study only showed moderate effi cacy, considering the high burden of the disease not only in the Philippines but also in Asia. The vaccine also showed a clinically important reduction of dengue hemorrhagic fever and the risk of hospitalization. Above all, its safety profi le is consistent with the result of the previous clinical studies assessing vaccine’s safety.

The Long Wait for an Eff ective Vaccine Against the Dengue Virus It actually took about 70 years to come up with a potentially-eff ective vaccine against dengue. Capeding cited various reasons on the slow progress of dengue vaccine development. One of the primary problems is the challenge to develop four combined immunogens since dengue is caused by four diff erent serotypes. In other words, the vaccine must be tetravalent to induce

“around 50 to 100 million people are affl icted by dengue annually, and over 2.5 billion people (over 40% of the world’s population) are at risk to be infected. Of those affl icted by the disease, 22,000 die”

A clinical trial staff of the Dengue Vaccine Study conducts a group orientation to study study participants and their guardians.

RITM UPDATE APRIL-JUNE 2014 5

a protective immune response against all four viruses.

“Another challenge is the absence of suitable animal model for dengue. Monkeys can be susceptible to dengue virus but they can only demonstrate viraemia (presence of virus in the blood) and does not actually present clinical disease. Thus, you really have to test the vaccine in humans,” explained Capeding

Furthermore, WHO, in their released guidelines for dengue diagnosis and control, inferred that there may have a possibility that a dengue vaccine could potentially cause severe disease (including Dengue Hemorrhagic Fever) in vaccine recipients if solid immunity was not established against all four serotypes. Therefore, vaccine design really requires intensive research to ensure that the dengue vaccine to be developed is safe and effi cient.

Also, since there is lack of a validated correlates of protection, clinical effi cacy studies are critical to fully understand the mechanism of protective immunity against dengue virus and confi rm that the candidate vaccines induce a protective immune response.

CYD-TDV Still a Work in Progress Despite the positive result of the Phase III clinical trial of CYD-TDV, Capeding clarifi ed that the candidate vaccine is still a work in progress.

“There is a very important component in this clinical trial which is the surveillance phase. Aside from the active surveillance phase, we also have the hospital surveillance phase where we will follow up the hospitalized dengue cases. It will run until 2017,” she explained.

Furthermore, the developer of the vaccine

is still waiting for the the Latin American leg of the clinical trial which was conducted among 9-16 year old children in Colombia, Mexico, Honduras, Puerto Rico and Brazil. It is expected to complement the Southeast Asian study.

Continuous monitoring will also be implemented even after the commercial release of the vaccine.

“There will be post-marketing surveillance and this is an SOP for all vaccines and drugs,’” added Capeding.

Other RITM Research Activities on Dengue Prevention and ControlAside from CYD-TDV effi cacy study, RITM performs other research projects on dengue control and prevention.

Another study headed by Capeding aims to identify protective and pathogenic immune responses against dengue virus (DENV) among infants. Studies show that primary DENV infection during infancy is more likely to lead to Dengue Hemorrhagic Fever and severe illness than during childhood or adulthood.

A study headed by Ms. Edelwisa Mercado and Dr. Fe Espino seeks to understand the genetic factors among humans that may aff ect the severity of dengue fever among

“CYD-TDV yielded a promising result as it showed a signifi cant reduction of 56.5% of dengue disease cases in the fi ve countries combined ”

FEATURE

Filipino children. The study focuses on association of dengue infection to the variation of human leukocyte antigens (HLA), a group of genes which are responsible for regulation of the human immune system.The Department of Medical Entomology is conducting a research to determine the insecticide susceptibility profi le of Aedes aegypti and Aedes albopictus and the possible development of resistance in these dengue vectors to ensure that all insecticide-based control strategies remain optimally eff ective.

A descriptive study, headed by Dr. Nelia Salazar, is also being conducted to describe the implementation of a Department of Interior and Local Government Memorandum which created an inter-agency cooperation strategy to reduce dengue cases in the country and to assess the outcome of the said dengue control interventions in six highly urbanized cities.

RITM’s Commitment to Combat DengueIn a tropical country like the Philippines where dengue is endemic, the situation could be worse if no appropriate research initiatives are conducted to complement the present control measures against the virus. Research activities on dengue are expected to inform measures to alleviate, if not immediately eliminate the burden of dengue in the country.

RITM, as the country’s lead agency for research in infectious diseases, is committed to conduct extensive and multidisciplinary research with the hope of contributing to the world’s fi ght against dengue.

As RITM joins the international community in the goal of eliminating the disease, the Institute hopes that the stories like those of Nelia’s would be less likely to be heard in the near future.

Dr. Rosario Capeding, principal investigator of the Dengue Vaccine Trial in the Philippines, gives an inspirational talk on the potential impact of the candidate dengue vaccine to the community of San Pablo City, Laguna.

6 RITM UPDATE APRIL-JUNE 2014

RITM Celebrates 33rd Anniversary

The Research Institute for Tropical Medicine (RITM) celebrated its anniversary on April 21, marking its 33rd year as the country’s lead institute for infectious disease

research.

A holy mass commenced the line-up of activities for the institute’s anniversary celebration. Recognitions for RITM staff were also given, including Loyalty Awards, Achievement Awards and Service Awards. Afterwhich, Drs. Leilani Senador, Ma. Teresita Gabriel, and Gracia Teodisio of the Department of Dermatology gave lectures on Leprosy. RITM staff enjoyed free movie screening of Frozen and Superman Returns and raffle prizes.

RITM was established in 1981 as the research laboratory of the Department of Health through the Executive Order No. 674, in order to conduct efficient and economical implementation of research programs on diagnosis control and treatment of tropical and infectious diseases.

1

4

5

6

7

8

2 3

Dr. Eric Tayag and Dr. Socorro Lupisan awarding plaque of recognition to former RITM Director, Dr. Olveda Dr. Gabriel, Dr. Socorro Lupisan, Dr. Eric Tayag strutting their dance moves for the program finale RITM Staff gamely grooving with Dr. Eric Tayag to the tune of Walk in the Club RITM Staff lining up to satisfy their sweet tooth with the free ice cream RITM Staff showing off their tickets to the free movie screenings Dr. Leilani Senador from the Department of Dermatology giving a lecture on Leprosy RITM staff receiving Loyalty Award to recognize their years of service in the Institute RITM staff receiving Service Award to recognize their efforts during the Post-Yolanda Emergency Response in the Visayas area

1

2

3

4

5

6

7

8

RITM UPDATE APRIL-JUNE 2014 7

The Medical Entomology Department and the Communication and Engagement Offi ce of RITM facilitated the Department of Health’s workshop on the development of dengue vector surveillance plan for the National Dengue Prevention and Control Program. The workshop was held at Ciudad Christia Resort, San Mateo Rizal, May 27-29.

This was the fi rst session of the three-series workshop that aims to come up with a policy that will support the national implementation of dengue vector surveillance in the Philippines. The workshop was attended by

RITM, in collaboration with the National Center for Disease Prevention and Control (DOH-NCDPC), the National Epidemiology Center and the Regional Epidemiology Surveillance Unit conducted the Dengue Surveillance Strakeholders’ Meeting at the Mariott Hotel, Pasay City on April 14-16.

The meeting aimed to develop active and sentinel-based dengue surveillance in all regions of the Philippines and to establish a framework for implementation of future plans of the National Dengue Control Program.

Among the topics discussed were the current dengue situation in the Philippines, partnership for National Dengue Surveillance and dengue research updates. A Regional Microplanning Session for dengue surveillance was also conducted. Dr. Lyndon Lee Suy, DOH-NCDPC’s Program Manager for Emerging and Re-emerging Diseases facilitated the session.

RITM Facilitates Workshop on Nat’l Dengue Vector Surveillance Plan

the Regional Health Offi ce coordinators. During the workshop, the participants identifi ed the gaps and issues on implementation of dengue vector surveillance in their regions; proposed solutions to their identifi ed problems and developed an action plan to eff ectively roll out the dengue vector surveillance activity across the country.

The drafted action plan will be the basis of discussion forthe next workshop with LGU offi cials and staff on November.

RITM Operationalizes its Communication and Engagement Office

RITM Sets up Clinical Trial Unit

To optimize RITM’s communication eff orts to its partners and the public, the Communication and Engagement Offi ce (CE Offi ce) was created through RITM Offi ce Order No. 213, S. 2013.

The CE Offi ce, under the Offi ce of the RITM Director, is tasked to implement RITM’s communication strategy. The strategy includes the implementation of campaigns that will establish and communicate RITM’s institutional identity, and highlight RITM’s contribution to public health

Tasked to develop and implement policies and procedures for the conduct of clinical trials in the institute, RITM created the Clinical Trial Unit (CTU) through the Offi ce Order No. 192, S. 2014. CTU will work in coordination with RITM’s other divisions and study groups, the Institutional Review Board and the newly established Research and Innovation Offi ce (RIO).

RITM Surveillance Unit FinalizesManual of Procedures

RITM holds Dengue Surveillance Stakeholders’ Meeting

To improve the public health impact of surveillance activities at RITM, the Institute’s Surveillance Unit (SU) organized a workshop for the development of the SU Manual of Procedures.

The workshop was held at the Bayleaf Hotel, Intramuros, Manila last June 10-11.

Dr. Eric Tayag, Director of DOH’s National Epidemiology Center highlighted the role of the RITM-SU in the surveillance eff orts of DOH especially during the outbreak of emerging infectious diseases.

The workshop was facilitated by Dr. Beatriz Quiambao, RITM’s Assistant Director and Head of SU, and Ms. Rowena Capistrano, Surveillance Unit Offi cer.

NEWSBITSRITM-CTU is further assigned to maintain a registry of the institute’s clinical trials and the trials’ personnel; ensure regular calibration of all clinical trial equipment maintained by RITM; and serve as liaison between the administration and clinical trial proponents. Dr. Mari Rose de los Reyes and Dr. Cristina Ambas were appointed as CTU Head and CTU Coordinator, respectively.

The CE Offi ce is further tasked with generation of content and execution of projects for RITM institutional marketing activities; development and distribution of RITM offi cial public information materials; and designing and implementation of internal communication activities.

4

5

6

7

8

Mr. Aldrin Reyes, Supervising Health Program Offi cer of the Department of Health gives the workshop’s opening remarks

8 RITM UPDATE APRIL-JUNE 2014

Maria Rosario Capeding, MD, head of the Microbiology Department and Principal Investigator of the Dengue Vaccine Clinical Trial in the Philippines is this year’s Dr. Jose P. Rizal Memorial Awardee for Research. The said recognition was awarded by the Philippine Medical Association. Dr. Capeding received a trophy designed by National Artist Napoleon V. Abueva, a gold medallion, free trip to the United States to attend the convention of the American Academy of Family Physicians, and P150, 000 worth of medicines that she can share with a civic organization of her choice.

Eleonor Fundan Avenido of the Immunology Department is one of the recipients of the Japanese Government-funded Monbukagakusho Scholarship for 2014. She is currently taking her Master’s Degree in Pharmaceutical Science at Nagasaki University, Japan.

Arthur Dessi E. Roman, MD of the Medical Department received a Joint Japan/World Bank Graduate Scholarship (JJ/WBGSP) for a Master’s Degree in Tropical Medicine at Nagasaki University, Japan.

Jun Ryan C. Orbina of the Molecular Biology Laboratory and Communication and Engagement Offi ce is one of the participant-scholars for the Global Leaders for Innovation and Knowledge Program of the Fujitsu-Japan-America Institute of Management Sciences. The program is a multi-campus course where the participants learn knowledge management in Japan; Hawaii, United States; Thailand; and Singapore.

RITMEA-AHW Elects New Officers

The RITM Employees Association-Alliance of Health Workers elected new offi cers for 2014

to 2017. The election was held on May 28-29. Gar-nering 220 votes, Rodolfo Perez was elected as President while Edgardo Damicog won as Vice President with 215 votes. Below is the complete list of the association’s new offi cers:

President: Rodolfo PerezVice President: Edgardo DamicogSecretary: Maria Charmaine RomuloTreasurer: Lennie AzoresAuditor: Pacita PimentelPRO: Ireneo Rayos Bernardo Garcia Edgardo Linsangan Carol TorresSgt. At Arms: Ricardo PrudencioBoard of Directors:Portia Alday Gloria June Quiñes Ruby Catubig Erminia Torio Mila Aligato Cristina Bustamante

RITMEA-AHW Officers for 2014-2016

Got a knack for writing? Do you have a story that you want to share with our colleagues and partners? Then be an RITM Update Contributor! Send your articles and/or photographs to ritmupdate@gmail.com and we will feature them in the next issue of RITM UPDATE.

Produced by:

RITM Update

Web: www.ritm.gov.ph Mail: 9002 Research Drive, Filinvest Corporate City Alabang, Muntinlupa City 1781 PhilippinesTel: (632) 809-7599 / 807-2628 to 32 Fax: (632) 842-2245

RITM Update is a quarterly newsletter published by the Research Institute for Tropical Medicine - Department of Health (RITM-DOH). For your feedback, e-mail us at ritmupdate@gmail.com.

to equipment standard and personnel training, the WHO commissioned expert will determine if the laboratory performs its regular operation according to WHO standard.

WHO conducts laboratory accreditation of the laboratories that test vaccine preventable diseases as part of global or regional program eff orts to eradicate, eliminate or control disease. This is to ensure maintenance of standards and reliability of the national reference laboratories around the world.

Tandoc added that “the process further provides a mechanism for identifying resource and training needs. Moreover, the accreditation process builds a strong relationship between the participating laboratory and the WHO laboratory network, which is composed of international experts – it is, thus a valuable learning opportunity for the participating laboratory.”

RITM Labs Receive...(from page 2)

Dr. Rosario Cepeding, head of Microbilogy Dept., receives the Dr. Jose P. Rizal Award trophy and gold medallion for research.

Sonia B. Sia, MD, head of the Antimicrobial Resistance Surveillance Laboratory received a full scholarship from the Department of Health for a Master’s Degree in Public Management at the Ateneo de Manila University.

Wilfredo Aure of the Medical Entomology Department was accepted to pursue his PhD in Entomology at the Universiti Sabah in Malaysia through a grant from Monkeybar Project, a multidisciplinary collaborative research project on zoonotic malaria, where Aure is also involved. The grant was funded by the London School of Hygiene & Tropical Medicine, a partner institution of the Monkeybar Project.

Cristino Narciso of the National TB Reference Laboratory and Neil Yabut of the Molecular Biology Laboratory had completed the one-year Training Program for Advanced Biorisk Offi cers (ABOT2). The training was organized by the University of the Philippines Manila Institutional Biosafety and Biosecurity Committee (UPM- IBBC), in partnership with the US Department of State Biosecurity Engagement Programme (BEP) and Philippine Biosafety and Biosecurity Association (PhBBA) to promote and strengthen laboratory biosafety and biosecurity.