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Up to 200 Filipino children risk severe dengue

Aedes Aegypti Mosquitoes (26444925321)based on three numbers: 730K vaccinated, 87% previously infected (link) and 2 of 1000 risk (link) of severe dengue according to Sanofi among those vaccinated but not previously infected: “The increased risk identified from the new analysis translated to two additional cases of ‘severe dengue’ out of 1,000 previously dengue-uninfected people vaccinated over five years of follow-up,” the company said in an emailed statement. Certainly not good, but a far cry from the panic in a video (link) by “major blogger” Sass Rogando Sasot implying that 700 thousand kids were at risk.

Who said what

997 children got sick after vaccination (link) say a Philstar headline – in the article it says that the Department of Health (DOH) reported that between March 18, 2016 and Aug. 20 of the same year, there were 997 “adverse events following immunization, 30 of which were considered serious cases that needed hospitalization.” The 30 serious cases included two deaths. But the DOH said these “were not related to the immunization program,” which was launched in early 2016. Other cases are claimed outside the DOH statistics, and insufficient monitoring is alleged.

There is also a difference between articles that claim WHO recommended Dengvaxia (link) and clarifications by WHO itself that it (linkdid not include a recommendation to countries to introduce the dengue vaccine into their national immunization programs. Rather, WHO outlined a series of considerations national governments should take into account in deciding whether to introduce the vaccine, based on a review of available data at the time, along with possible risks. Among other things recommending to vaccinate in areas with over 70% dengue exposure.

When what happened

Who published its position on the dengue vaccine in July 2016, based on a preliminary advice by an expert group from April 2016. The Philippines started vaccinating in April 2016 (link) – ignoring or setting aside opinions like those of UP College of Medicine Prof. Dr Antonio Dans, who warned that while the vaccine could reduce the number of dengue cases, it could later increase the disease’s severity, a phenomenon known as “antibody- dependent enhancement” – or Dr. Anthony Leachon who said the DOH should first wait for the WHO study – which came out in July 2016.

Further doubts Dr. Leachon had were also about long-term safety (link) especially with previously non-infected persons. Studies in September 2016 (link and link) and articles in CNN (link) and Voice of America (link) in late 2016 also mentioned those risks, but the DOH under a new administration continued the program (link) while having doubts on efficacy. There was a Senate hearing in December 2016 (link) but it seems it was more about the way the program was funded.  The decision to end the program after the third round of vaccination was taken in May 2017 (link).

Still, it seems that 67 thousand kids in the Central Visayas got vaccinated in August 2017 (link). Other countries like Malaysia (link, June 2016) and India (link, Oct. 2016) were more reluctant – even in April 2017 (link) and November 2017 (link). Brazil was the other country that vaccinated, the observations from there are going to be interesting. Sanofi was right to pull the brakes in late November 2017. Imagine if, let us say 20 million Filipinos had been vaccinated at a prevalence of 80% – that would have been 0.2% of 20% of 20 million at risk of severe dengue, meaning 8000.


Science and Risk

ICE4 FrontA major derailment happened in Eschede in 1998 (link) when the German speed train or ICE was hardly a decade old. A train derailed and folded together at high speed due to wheel fracture (link). 101 people died, tabloids reported scenes of horror. Yet no witch-hunts. Causes (link) were analyzed and consequences (link) – also legal ones – were decided upon. The program was not stopped, instead ICE model 1 was improved, later new models came out, new routes were built. This Friday, the Munich-Berlin route (link) shall cross 623 km in about 4 hours. Using ICE 4 (link) trains.

A book I read (link) mentions how the aircraft industry and airlines improved a lot of things by analyzing black boxes from airplane crashes and other incidents – but mentions issues in introducing similar measures in medicine. I wonder if the touch of arrogance attributed to the medical profession in the book also applies to the pharmaceutical industry. Many circles also accuse the pharma industry using third world countries as guinea pigs. But only a modern, evidence-based approach will help prove what is true. And pin down possible accountability. 

Capulet and Montague

There will probably be a hearing in aid of legislation at the Philippine Senate – once again. Which I do not expect much from. The usual political stuff, names of Presidents and Health Secretaries. VACC loudly claiming deaths NOW from last year (link) added to the fray, hardly looking credible.

Better not just allege deaths without proof as in hard evidence. Sanofi might go for an international case. Not like the De Lima case or the wannabe impeachment against Sereno. Real lawyers will be needed – like Sereno for Fraport or Carpio for ITLOS. The kind of talent the country hates (link).

One should also see that around half of the vaccinations were during the Aquino administration, the other half during the Duterte administration. Finding out the entire truth will be a long process – if the Filipino public is really interested in the truth and not just own emotional or group needs.


Galileo and Newton

The modern world is too complex for the petty village mentality on show in Filipino politics, the lack of getting the big picture. India seemed to have dealt with Dengvaxia way more maturely – but then again they send rockets into space (link). How could one deal with this in a rational manner?

200 kids are at risk, if one is to believe a certain set of numbers. What is the solution? First – monitor things. Senator Hontiveros wants that to happen in form of a database (link). Possibly, measures from this experience could be used to improve health monitoring in the Philippines.

Second – all lab data on present alleged cases (link) should be gathered in a transparent manner. Just in case there really was negligence on part of Sanofi, it can be proven in an auditable way. There is a certain self-discipline needed here, as Filipinos very often lack objective attitudes.

The Big Picture - The Noun ProjectThird – look at the big picture. Few newspapers, few experts, few leaders in the Philippines are good at that. Data is not information is not knowledge is not wisdom. This Rappler timeline (link) of what happened locally is at least information. Knowledge? We know a little, need to learn more.

In some papers I read about 3.5 billion being for vaccines only. In some I read it was for the vaccines and the entire program including monitoring for five years. Some state that monitoring was insufficient in the beginning. How was the experience in Brazil? And the more cautious countries?

India wanted to make own tests with monkeys before starting, later on Assam state decided to make a random test to check for at least 70% prevalence before going for vaccination. Malaysia wanted to wait for fourth phase tests. All in the sources quoted above. Where is the best balance?

Finding scapegoats is too easy as well – especially if the issue could be caused by weak institutions with systemic problems (link) that go beyond individual leaders. Maybe Dengvaxia could be an opportunity to learn and reform some things? There is a lot of ground to be covered I think.

Irineo B. R. Salazar
Munich, 6 December 2017

53 comments to Up to 200 Filipino children risk severe dengue

  • https://www.facebook.com/sylvia.claudio.5/posts/10155144664962014

    From Junice L. Demeterio Melgar

    I was at the Senate hearing yesterday to be with former friends and colleagues in the DOH for what was supposed to be an investigation on the use of Dengvaxia. I will be back with another personal assessment of the issue, but before that, here is a balanced, down-on-the-ground, physician’s view on the matter.

    —————–
    Forwarded Post
    from Dr Edcel Salvana:, infectious Disease consultant UP Cm
    So I’m going to stick my head out because I feel there is a lot of confusion going around on the dengue vaccine again. This is my interpretation of the Sanofi release. For the record, I am an infectious diseases physician who deals with dengue on a daily basis. I am not a trained epidemiologist, but I do have some research expertise. I do not work for Sanofi and have never received any money from them. The reason I am speaking up is because I feel this vaccine has been demonized and that the ones who would benefit from it may not take it because of the uncertainty surrounding the interpretation of the recent statement.
    1. First of all, the vaccine was never meant to be given to seronegatives, based on the understanding that it would set up the antibody dependent enhancement (although there was no cytokine evidence of this in the severes). That is why it is only for use in high prevalence countries.
    2. There is a proliferation of igm and igg dengue test kits in the market which are meant for diagnosis of active dengue, not necessarily past dengue infection where the titers are much lower. The best test will be an elisa done in a proper hospital or research lab. The vast majority of lateral flow rapid assays done by diagnostic labs are not designed to detect past infection in someone who does not have active dengue. Therefore, there is no readily accessible reliable way for a physician to diagnose past infection in someone who does not have dengue. If the test is positive then it is useful, but if it is negative it is not certain.
    3. The statement reiterated the efficacy of the vaccine up to 6 years, and this is a good thing. If you have started the series, you probably should complete it otherwise you wont get the full benefit. We need to emphasize this because people may not complete their vaccination because of the uncertainty.
    4. We are talking of a safety SIGNAL, not a statistically significant harm. This is why they used the word “could harm” versus definitely harms. No one has died from this. But lots of people have died from dengue. You decide which is a bigger problem and if your risk of getting dengue is higher you should take the vaccine within the recommended parameters. Put another way, we are talking about definite benefit versus possible harm.
    5. I agree this should not have been used immediately for mass vaccination until after SAGE released its recommendations. Whatever DOH’s reason for going ahead with it, they will have to explain. However this should not discredit the scientific evidence that the vaccine works when used correctly. Based on the seroprevalence studies in the Philippines, the seroprevalence of at least one dengue infection is above 90% in those ages 12 and above. And if you have had at least one episode of dengue (like me), you should absolutely not hesitate to get the vaccine. The vaccine decreases the risk of severe dengue in this group of people by about 90% for sure. Statistically significant.
    Bottom line, this is a GOOD vaccine when used correctly. Talk to your doctor if it is appropriate for you. Only you can make decisions about your health, but you need to make an informed decision.

    • https://www.facebook.com/sander.bondoc/posts/1629305447126750

      PNOY OPENING STATEMENT IN THE SENATE HEARING ON DENGUE VACCINE

      Nagsimula po ang pagtutok ko sa Dengue sa Pilipinas matapos kong matanggap ang memo ni Secretary Ike Ona, dated 23 Aug. 2010. Sa briefing sa akin, lahat ng serotypes o uri ng Dengue narito daw po sa Pilipinas; hindi din daw seasonal ang Dengue, at walang gamot para rito. Malaon po, sasabihin sakin ni Sec. Ona na may nagde-develop ng vaccine para sa lahat ng strain.
      Matagal na ngang problema ang Dengue sa atin. Nung bata pa ako, may sakit na tinatawag na H-Fever. Pag nagkwekwentuhan ang matatanda tungkol sa H-Fever, madalas kasunod nun ang pagsabing may naospital na nangangailangan pa ng blood transfusion. Itong H-Fever, atin pong napag-alaman, ay ang Philippine Hemorrhagic Fever, na mas kilala ngayon bilang Dengue.
      Pag tinamaan ka ng isang serotype ng Dengue, magiging immune ka roon pero hindi sa ibang strain. Naibalita po sakin: May isang dating Speaker of the House na naospital nang 2 beses dahil sa Dengue, at sabi po niyang mukhang nagkaroon pa ng pangatlong uri sa mga taong lumipas. May isa namang European ambassador na na-assign dito sa atin, na sa pagmamahal niya sa Pilipinas ay gumawa ng brochure ng tourist destinations natin para sa mga kababayan niya sa kanilang lenggwahe. Siya po, 2 beses nagka-Dengue. Tayong lahat rito, siguradong may kakilalang na-Dengue ng minsan o ilang ulit.
      Sa memo po ni Sec. Ona, naka-highlight ang 5 rehiyong may pinaka-mataas na ulat ng Dengue. 3 sa 5, higit 100% ang increase. May isa po, 1409.5% increase o 14 na beses ang itinaas. Di po maipaliwanag kung bakit 14 times umangat ang kaso ng Dengue sa Region 8, na di naman kasing congested tulad ng Metro Manila o Metro Cebu. Mas kalat ang populasyon ng Region 8, at mas malayo ang ibyabyahe ng lamok na may Dengue, kumpara rito sa Metro Manila na dikit-dikit ang bahay. Tanong: Kung sa hindi highly urbanized na lugar, 1409.5% increase, paano na sa talagang dense at urbanized?
      Ang nakakatakot dito: Kung tinatayang may 200,000 cases ng Dengue kada taon, at posibleng umangat ng 14 beses ang bilang tulad sa nangyari sa Region, ang potensyal na pwedeng magka-sakit ay 2.8 milyon. Yan po ang dami ng Pilipino na baka kailangan ng blood transfusion, na baka kailangang ipasok sa mga ospital, na baka kailangang suportahan ng ating gobyerno, lalo na kung siya ay matanggal sa trabaho at arawang swelduhan. Diin ko po: Noong panahong iyon, inuumpisahan pa lang natin ang pagsaayos sa Philhealth. Sa kabuuan ng aking termino, sa mga pagkakataong nadadaan ako sa intersection ng Quirino at Osmeña, may nakikita akong electronic billboard na sinasabi: May dengue ka, ang halaga 20,800 na gastos sa ospital; kung wala, kumuha ka ng medical health insurance. Yun pa ay advertisement ng isang health insurance provider. Kung di po maipaliwanag kung bakit sumipa ng 14 times ang Dengue sa Region 8, di po natin masasabi kung paano natin mapipigilan ito. Ang estima para sa isa sa mga worst case scenario: Sa 2.8 million na kataong na-Dengue, i-multiply mo sa 20,800, ang buong gastos: 58.2 billion pesos.
      Ang tugon po ng gobyerno sa mga panahong iyon: Tinigil natin ang indiscriminate fogging na itinataboy ang lamok na may Dengue sa kabilang barangay. Nag-activate ang DOH ng Dengue express lanes sa mga ospital ng gobyerno. Nag-install ang DOST ng Insecticide-Treated Screens at Mosquito Ovicidal/Larvicidal (OL) Traps. Yung National Dengue Prevention and Control Program, malinaw ang resulta: Bumagsak mula sa 1,057 nung 2010 patungong 317 sa Oktubre 2015 ang bilang ng namatay dahil sa Dengue.
      Dec. 2015, nagpunta po ako sa Paris para sa COP21, kumperensya ng mga bansa para tugunan ang climate change. Gaya ng lahat ng byahe natin, kinausap natin ang maraming namumuhunan, partikular na ang Vivapolis, Airbus, Jacobi Carbons, kumpanyang CRH, tumungo sa Usine IO, at pati na rin ang Sanofi. Sinabi sa atin noon na ready na ang Sanofi sa bakuna.
      Yung ganitong uri ng gamot, maraming taon inaabot ang development para masiguro talaga ang efficacy at lalo na ang safety. Naalala ko po bilang halimbawa: Noong 1960s, may gamot na Thalidomide, na ibinenta para sa morning sickness, na nagbunsod sa deformities sa mga sanggol ng mga babaeng kumuha nito. Kaya nagpasa noong 1962 ang U.S. Congress ng Kefauver-Harris amendments para sa Federal Food, Drug, and Cosmetic Act, at naghigpit ng mga proseso ang U.S. FDA. Ang intindi natin sa Dengvaxia, natapos na ang lokal at international processes nito. Tiningnan namin ang U.S. FDA; may 5 steps ito: Discovery and Development, Preclinical Research, Clinical Research, FDA Review, at Post-Market Safety Monitoring. Paliwanag sa akin, dumaan ang Dengvaxia sa isa sa mga phases ng U.S. FDA. Diin ko na rin po: Di lang Pilipinas ang nag-apruba sa Dengvaxia. Nauna sa atin ang Mexico at Brazil. Diin ko lalo: Sa aking pakiwari, at pag-unawa, dumaan na po ito sa lahat ng proseso para malaman ang kanyang efficacy at mas importante ang kanyang safety.
      Nung ilunsad natin ang programa sa Zambales nung April 2016, ipinakita sa akin ang isang presentation na nakasaad ang ilang bakunang dekada nang napapakinabangan ng mga may-kaya pero kailan lang naibigay sa publiko. Gaya po ng bakuna para sa Polio, Rabies, at Pneumonia. Diin ko lang po, ang obligasyon ng gobyerno, na siguruhin, gaya ng sinabi ni President Magsaysay na: “Those who have less in life should have more in law.” Hindi ko po naisip ipagkait sa pinaka-nangangailangan at nanganganib ang proteksyon ng bakuna.
      Sa lahat po ng usapin ngayon ukol sa Dengvaxia, kung di man diretsong sinasabi, ang pakiwari ay kung nagpa-bakuna ka, tila nalalapit ka sa pinaka-malubhang uri ng Dengue. Tila nalalapit ka sa kamatayan. Nung kami po ang namamahala, malinaw sa amin: kung tatakutin mo nang husto ang tao, darating ang punto na di na sila makakakilos dahil sa kaba. Klaro po sa amin noon, trabaho ng gobyerno na pakalmahin at suportahan ang Pilipino. Kaya nung Pangulo ako, kinastigo ko ang mga opisyal na mahilig magpakaba ng sambayanan. Gaya po nung 2014 nung may isyu tayo tungkol sa MERS-Coronavirus. Pinaigting nga po natin ang surveillance at pagtutok sa sakit.
      Diin ko lang po: Bago nagdesisyon ang gobyerno sa Dengvaxia, habang nagdedesisyon, at maski pagkatapos magdesisyon, wala pong nagparating sa akin ng pagtutol sa naturang bakuna. Kaya natin inilunsad ito sa NCR, CALABARZON, at Central Luzon, dahil ayon sa datos ng DOH, ito po ang tatlong pinaka-apektadong mga rehiyon nung 2015 kaugnay ng Dengue.
      Kung di lumabas itong sinabi ng Sanofi, at nagdesisyon akong hayaan na lang na magdusa pa ang karaniwang Pilipino gayong may bakuna na, palagay ko ngayon, iba ang tanong ninyo at asunto sakin: Bakit mo pinabayaan ang kababayan mo? Paano ko ipapaliwanag sa mga nanay ang pagkamatay sa kanilang mga anak, kung meron na palang proteksyon na ipinagkait sa kanila?
      Ulitin ko po: 2010 pa lang po may problema na tayo sa Dengue. 1409% ang paglobo nito sa Region 8, na posible ring mangyari sa buong bansa. Nangako akong iiwan ko ang Pilipinas na mas maganda kesa sa aking dinatnan. Kaakibat noon ang pagbawas sa gastos, kaba, at pasanin ng aking mga Boss, ang sambayanang Pilipino.
      Maraming salamat po.

      • https://www.rappler.com/nation/191364-conflict-janette-garin-fec-dengvaxia-dengue-vaccine?utm_source=facebook&utm_medium=social&utm_campaign=nation

        During the hearing, DOH secretary Janette Garin defended her decision to start vaccinating public school students in the National Capital Region, Central Luzon, and Calabarzon with Dengvaxia in April 2016.

        Senate blue ribbon committee chairperson Richard Gordon pointed out in the hearing that the Formulary Executive Council (FEC) – a panel of top Filipino experts that identifies which medicines and drugs the government may use and procure – never recommended mass use of Dengvaxia.

        “FEC, yes, they are experts in their own fields. But during that time, but even until now, in aid of legislation, your honor, tingnan po natin ang palagi pong paulit-ulit na conflict between FEC and the Department of Health. Dahil doon po sa batas nakasaad na dapat ang FEC pinapatawag ang departamento, ang mga internal and external experts,” said Garin.

        (FEC, yes, they are experts in their own fields. But during that time, since this is an investigation in aid of legislation, let’s look at the longtime conflict between the FEC and the Department of Health. Because the law states the FEC must call for the department as well as internal and external experts.)

        She said she had consulted other experts including DOH’s own program directors as well as Philippine Society for Microbiology and Infectious Diseases and Philippine Pediatric Society Incorporated, which advised her it would be safe to use Dengvaxia in the national immunization program.

        “Ang tiningnan po namin, hindi lang po ‘yong proteksiyon na 65.5% (We checked not just the protection rate 65.5%), but what was very important for us was the 80.8% reduction in hospitalization and the 90.2% reduction in severity,” said Garin.

        She said it “wasn’t true” that the vaccine’s safety and efficacy was being questioned, arguing that the Food and Drug Administration will not approve Dengvaxia’s sale in the country had it been otherwise.

        But the FEC members were not sold on the safety, efficacy, and cost-effectiveness of Dengvaxia when they met on January 7 and 25, 2016, and on February 1, 2016.

        Created by then President Fidel Ramos through Executive Order 49, the FEC is mandated to determine which drugs should be part of the National Formulary, a list of drugs that the government can buy and use.

  • https://www.rappler.com/nation/191334-senate-probe-dengue-vaccine-bad-science?utm_source=facebook&utm_medium=social&utm_campaign=nation

    Antonio Dans, an epidemiologist at the Philippine General Hospital (PGH), said the warning that there could be negative effects on patients with no previous dengue flu was “initially ignored” and was only recognized later on.

    “In my own opinion, the whole problem started with bad science. In our opinion, that’s the root of the problem. And that bad science, there were already signals of harm in seronegative patients. And it was ignored initially and it led to the delayed recognition of that harm. And then we were led to patients who were uninformed,” said Dans, also a scientist at the National Academy of Science and Technology (NAST).

    http://newsinfo.inquirer.net/952403/health-dengue-anti-dengue-vaccination-doh-who-dengvaxia-sanofi-pasteur?utm_campaign=Echobox&utm_medium=Social&utm_source=Facebook#link_time=1513229492

    WHO Country Representative Dr. Gundo Aurel Weiler explained during the hearing of the Senate blue ribbon committee the processes being undertaken by the organization when introducing a new vaccine.

    First, he said, WHO convenes a group of expert called a strategic advisory group, which is tasked to review all available data and make recommendations on the possible use of a vaccine in countries.

    Weiler said the advisory group convened in April 2016 and made recommendations in the middle of the month of the same year. These recommendations, he said, were adopted by the WHO, which was later published in July 2016.

    http://newsinfo.inquirer.net/952379/health-dengue-anti-dengue-vaccine-doh-president-noynoy-aquino-dr-anthony-leachon?utm_campaign=Echobox&utm_medium=Social&utm_source=Facebook#link_time=1513225275

    “How could you blame the President if he was fed (with) wrong information?”

    This was the reaction of a health reform advocate when asked if former President Benigno S. Aquino III should be held liable for the government’s controversial P3.5billion anti-dengue immunization program, which implementation began during his term.

    “I was asked the other day, whether the ex-president and secretary of health is liable for this one. My answer is basically, if the bad science or wrong information has been fed to the president, how could you blame the President if he was fed by wrong information and even WHO (World Health Organization) or even (former Health) Secretary (Janette) Garin?” Dr. Anthony Leachon told the panel.

    Before this, another health expert from the National Academy of Science and Technology (NAST) clarified that the main problem was that “bad science mixed with politics.”

    “Because there was no policy to separate politics and science the FDA is under the DOH (Department of Health), then we lose the check and balances. FDA should be independent from DOH,” Dr. Antonio Dans said.

    http://www.philstar.com/headlines/2017/12/14/1768344/who-release-report-phl-dengue-vaccine-program

    MANILA, Philippines — The World Health Organization is preparing a new position paper to address the dengue vaccine controversy in the Philippines.

    Gundo Aurel Weiler, WHO country representative, said at the resumption of the Senate probe on the Dengvaxia controversy the global organization is “seeking, mobilizing its expert committees, in seeking advice from them” on the vaccination program.

    Two groups composed of experts are looking at the data in the Philippines.

    https://www.reuters.com/article/us-sanofi-dengue-science-insight/did-sanofi-who-ignore-warning-signals-on-dengue-vaccine-idUSKBN1E7072

    Four decades ago, Dr. Scott Halstead, a leading figure in dengue research, first proposed that antibodies from an initial exposure to one of four types of the disease could increase the risk of a potentially lethal complication called severe dengue when a person was infected a second time, a process know as antibody-dependent enhancement or ADE.

    This phenomenon could make development of a dengue vaccine tricky.

    Rather than being protective, a shot given to someone who had never had dengue could act like a first infection, increasing their risk of severe dengue when they were exposed a second time.

    http://www.philstar.com/headlines/2017/12/14/1768343/aquino-no-one-objected-dengvaxia-use

    No one came forward to express their objection against dengue vaccine Dengvaxia when the previous administration decided to roll out its national immunization program, former President Benigno Aquino III said Thursday.

    Facing the Senate Blue Ribbon and Health committees, Aquino defended his administration’s controversial dengue vaccination program, which was launched in April 2016.

    http://www.gmanetwork.com/news/news/nation/636541/noynoy-admits-he-wasn-t-aware-of-sanofi-controversies/story/

    Former President Benigno Aquino III on Thursday said he wasn’t made aware of the controversial issues faced by Sanofi Pasteur, manufacturer of controversial Dengvaxia dengue vaccine, when he met with the pharmaceutical company’s officials twice during his administration.

    Senator Richard Gordon, chairman of the Senate blue ribbon committee investigating the P3.5-billion dengue vaccination program, enumerated a list of charges against Sanofi in other parts of the world.

    • http://newsinfo.inquirer.net/237507/dengue-cases-in-philippines-up-by-16 (2012 article)

      ..More and more Filipinos are infected with the dengue virus, largely disproving President Benigno Aquino’s claim in his State of the Nation Address (Sona) that the Philippines is on its way to managing the deadly mosquito-borne disease.

      The Department of Health (DOH) on Thursday reported a 16-percent spike in dengue cases in the country this year..

      ..The number of deaths from the dengue virus also rose to 328, which is higher than the 293 cases recorded during the same period last year.

      Most of the cases centered in Metro Manila with 11,476. This was followed by Calabarzon with 7,265 and Central Luzon with 7,044…

      In his Sona, Aquino praised the measures made by the DOH and the Department of Science and Technology to curtail dengue, singling out for special mention Health Secretary Enrique Ona and Science and Technology Secretary Mario Montejo.

      • http://www.who.int/immunization/sage/meetings/2016/april/2_Smith_Clinical_Trial_Results_SAGE.pdf

        Status of CYD-TDV (as of 4 April 2016)
        • Licensed by 5 countries
        – 4 in Latin America (Mexico, Brazil, El Salvador, Paraguay)
        – 1 in Asia (Philippines)
        • Indication varies
        – 9-45 years in 4 countries
        – 9-60 years in 1 country (Paraguay)
        • Vaccine introduction in one country (Philippines)
        – Routine, school-based program targeting 4th grade children
        (9-10 year olds) in 3 highly endemic regions (~1,000,000 children)

        CYD 14 Asia – 5 countries, 11 sites, 2-14 years, 10275 volunteers
        CYD 15 Latin America – 5 countries, 22 sites, 9-16 years, 20869 volunteers

        CYD 14 started June 2011, active phase ended December 2013, estimated end date Nov. 2017
        CYD 15 started June 2011, active phase ended April 2014, estimated end date April 2018

        GACVS also emphasized the importance of further monitoring the risk of dengue requiring hospitalization (particularly severe dengue) in older individuals who are serologically naive at the time of vaccination.

        http://www.who.int/immunization/research/development/dengue_q_and_a/en/

        CYD-TDV has been evaluated in two Phase 3 clinical trials (CYD14 in five countries in Asia and CYD15 in five countries in Latin America). Together, these trials included over 35,000 participants aged 2 to 16 years: ages at first vaccination were 2 to 14 years in CYD14, 9 to 16 years in CYD15. In each of these trials, participants were randomized to vaccine and placebo in a 2:1 ratio. The study protocols included an active phase of follow-up for one year after the last dose of vaccine in the series (25 months from dose 1) and include a hospital-based follow-up period of four additional years, which is ongoing.

        http://www.who.int/wer/2016/wer9130.pdf?ua=1

        CYD-TDV has been evaluated in 2 parallel Phase 3 randomized clinical trials, known as CYD14 and CYD15.
        CYD14 was conducted at sites in 5 countries in Asia
        (Indonesia, Malaysia, Philippines, Thailand, and Viet
        Nam), with 10 275 participants aged 2–14 years at first
        vaccination.28 CYD15 was conducted at sites in 5 countries
        in Latin America (Brazil, Colombia, Honduras,
        Mexico, and Puerto Rico (USA)), with 20 869 participants
        aged 9–16 years at first vaccination.29 In each of
        these trials, participants were randomized to receive
        vaccine or placebo (0.9% solution of sodium chloride)
        in a 2:1 ratio. The study protocols included active
        surveillance for 13 months after the last dose of vaccine
        in the series (i.e. 25 months from dose 1) for the primary
        efficacy endpoint and included a hospital-based surveillance
        period of 4 years for additional safety evaluation,
        which is ongoing.

        Detailed analysis of the immune response, including an
        assessment of the serological status at the time of study
        enrollment, was conducted in a subset of both clinical
        trial cohorts. Participants with PRNT50 >10 against one
        or more serotypes were considered seropositive at baseline,
        which was interpreted as evidence of previous
        exposure to at least 1 of the 4 dengue viruses.

        http://www.denguevirusnet.com/vaccine-research.html

        CYD-TDV
        CYD-TDV is a live attenuated tetravalent chimeric vaccine made using recombinant DNA technology by replacing the PrM (pre-membrane) and E (envelope) structural genes of the yellow fever attenuated 17D strain vaccine with those from each of the four dengue serotypes. Ongoing phase III trials in Latin America and Asia involve over 31,000 children between the ages of 2 and 14 years. In the first reports from the trials, vaccine efficacy was 56.5% in the Asian study and 64.7% in the Latin American study in patients who received at least one injection of the vaccine. Efficacy varied by serotype. In both trials vaccine reduced by about 80% the number of severe dengue cases. An analysis of both the Latin American and Asian studies at the 3rd year of follow-up showed that the efficacy of the vaccine was 65.6% in preventing hospitalization in children older than 9 years of age, but considerably greater (81.9%) for children who were seropositive (indicating previous dengue infection) at baseline. The vaccination series consists of three injections at 0, 6 and 12 months. The vaccine was approved in Mexico, Philippines, and Brazil in December 2015, expected to be the first among the 20 countries in the coming weeks. Tradenamed Dengvaxia, it is approved for use for those aged nine and older and can prevent all four serotypes.

        http://business.inquirer.net/215327/ph-plays-key-role-to-fight-dengue-fever

        He said: “The Philippines participated in all three phases of the vaccine’s clinical development and of the 40,000 volunteers from around the world, 3,500 children were from the Philippines, setting up clinical trial sites in Alabang, Muntinlupa City (Phase 1); Barangay Del Remedios in San Pablo City (Phase 2); and Barangay Guadalupe in Cebu City along with Barangay Del Remedios (Phase 3). So researchers and volunteers here already knew its safety profile and effectiveness even before it was cleared for worldwide release.”

        https://www.rappler.com/science-nature/life-health/127318-doh-dengue-vaccine-safety

        Of the total 200,415 dengue cases recorded in the country from January 1, 2015 to December 31, 2015, 94,883 were recorded in these 3 regions: 25,208 from NCR, 35,966 from Central Luzon, and 33,709 from Calabarzon.

        https://www.biopharmadive.com/news/india-may-require-more-clinical-trials-for-sanofis-dengue-vaccine/418674/

        ..A top committee at the Indian Ministry of Health rejected Sanofi’s request to waive further late-stage trials for its dengue vaccine dengvaxia, reports The Economic Times. Two lower panels had supported granting a waiver based on Sanofi’s phase 2 studies..

        Sanofi has conducted phase 3 trials in other countries and sought to waive the requirement for locally conducted trials in India. The so-called apex committee decided evidence was not sufficient to grant an exemption however, according to The Economic Times..

        http://www.nejm.org/doi/full/10.1056/NEJMoa1506223#t=article

        A recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) has been assessed in two phase 3 randomized efficacy trials involving more than 31,000 children between the ages of 2 and 14 years in the Asian–Pacific region (CYD14 trial) and between the ages of 9 and 16 years in Latin America (CYD15 trial).1,2 The vaccine was administered in three doses: at baseline, at 6 months, and at 12 months. Vaccine efficacy against virologically confirmed dengue and safety were assessed during a 25-month efficacy surveillance phase (i.e., until 13 months after the third dose was administered). Reactogenicity and immunogenicity were also assessed in a subgroup of participants.1,2 Vaccination significantly reduced the incidence of virologically confirmed dengue and showed acceptable safety and reactogenicity profiles, findings that were consistent with earlier results.

        In the ongoing longer-term follow-up (from year 3 to year 6) to assess safety, we are monitoring the incidence of hospitalization for dengue as a surrogate end point for disease severity in order to evaluate a potential predisposition in vaccinated persons to increased severity of disease.3 In addition, we invited the 4002 children between the ages of 4 and 11 years from a single-center phase 2b trial (CYD23) in Thailand that had a study design similar to that of the CYD14 and CYD15 trials to participate in a separate study (CYD57) of 4 years of follow-up in which we are assessing safety in a similar way to the way it is being assessed in the two phase 3 trials.4 Here we report the interim analyses of data from the long-term safety phase and integrated analyses of data from the efficacy surveillance phase to provide a global view of the clinical profile of the CYD-TDV dengue vaccine.

        https://www.researchgate.net/publication/51483013_From_research_to_phase_III_Preclinical_industrial_and_clinical_development_of_the_Sanofi_Pasteur_tetravalent_dengue_vaccine – July 2011

        Dengue vaccine development has reached a major milestone with the initiation, in 2010, of the first phase III clinical trial to investigate the Sanofi Pasteur CYD tetravalent dengue vaccine (TDV). The CYD TDV candidate is composed of four recombinant, live, attenuated vaccines (CYD-1-4) based on a yellow fever vaccine 17D (YFV 17D) backbone, each expressing the pre-membrane and envelope genes of one of the four dengue virus serotypes. The vaccine is genetically and phenotypically stable, non-hepatotropic, less neurovirulent than YFV 17D, and does not infect mosquitoes by the oral route. In vitro and in vivo preclinical studies showed that CYD TDV induces controlled stimulation of human dendritic cells, and significant immune responses in monkeys. Scale up and industrialization are being conducted in parallel with preclinical and clinical development to fulfill the needs of phase II/III trials, and to anticipate and facilitate supply and access to vaccine in the countries where the dengue disease burden makes it an urgent public health priority. The vaccine has now been administered to more than 6000 children and adults from dengue endemic and non-endemic areas and no safety concerns have arisen in any of the completed or ongoing trials. A three-dose vaccination regimen induces an immune response against all four serotypes in the large majority of vaccinees. Preexisting flavivirus immunity favors quicker and higher immune responses to CYD TDV, without adversely effecting clinical safety or increasing vaccine viremia. The observed level and nature of the cellular immune responses in humans are consistent with the good safety and immunogenicity profile of the vaccine. Preliminary results of an ongoing, proof-of-concept efficacy and large scale safety study in Thai children are expected by the end of 2012. Here we discuss the different steps and challenges of developing CYD TDV, from research to industrialization, and summarize some of the challenges to the successful introduction of a dengue vaccine into immunization programs.

        https://www.rappler.com/nation/78459-aquino-ona-resignation

        Ona was also taken to task for clinical trials he ordered in September involving the controversial ActRx TriAct, an anti-dengue treatment. The drug has not yet been registered with the Food and Drug Administration as food, drug, or supplement.

        http://opinion.inquirer.net/80793/that-denguemalaria-drug

        One of the issues being raised against Health Secretary (on leave) Enrique Ona was the approval for testing on humans of an experimental drug that uses a combination of herbal drugs artemether, artesunate and berberine, under the name “ActRx TriAct” for the cure of both dengue and malaria.

        https://www.europeanpharmaceuticalreview.com/news/37458/sanofi-pasteurs-dengvaxia-approved-in-the-philippines/

        ..“Approval of the first dengue vaccine in Asia, which bears 70% of global disease burden, is a major milestone in dengue prevention and public health,” notes Olivier Charmeil, President and CEO of Sanofi Pasteur. “Approval of Dengvaxia in the Philippines, following closely the first approval in Mexico, is further evidence of Sanofi Pasteur’s long-standing commitment to introduce this innovative new vaccine first in countries where dengue is a major public health threat.”..

        ..“Prevention of dengue is an urgent and growing medical priority in the Philippines,” says Dr May Book Montellano, President, Philippine Foundation for Vaccination. “Vaccination is widely accepted as one of the most cost-effective ways to reduce the spread of infectious diseases like dengue. The approval of Dengvaxia, the world’s first dengue vaccine, in the Philippines will be a critical addition to the ongoing public education and vector control efforts currently directed towards dengue prevention in our country.”..

        https://www.ncbi.nlm.nih.gov/pubmed/25966916 – Aug. 2015

        BACKGROUND:
        Dengue is a major public health concern in pediatric populations in endemic regions. A recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) is under development for the control of dengue with a 3-dose (0-6-12 month) vaccination schedule.

        METHODS:
        In this controlled phase II trial conducted in the Philippines, 210 toddlers aged 12-15 months were randomized to 4 groups: 3 groups received the CYD-TDV vaccination schedule and a measles, mumps and rubella (MMR) vaccine given either concomitantly with the first CYD-TDV dose or 1 month earlier; 1 group received 3 active control vaccines. Safety and reactogenicity were assessed after each dose. Immunogenicity was assessed 30 days after vaccinations using the plaque reduction neutralization test against dengue and enzyme-linked immunosorbent assay methods against MMR antigens.

        http://www.sciencedirect.com/science/article/pii/S0264410X15014103

        The month of November 2014 saw the successful achievement of a critical phase of an ambitious and challenging program that had been launched 20 years before, supported by an overall investment of more than one billion Euros, and which mobilized more than 1000 people in a large number of countries across different continents: for the first time in human history, a robot successfully landed on a comet. Despite difficulties and uncertainties, Philae and Rosetta so far have achieved most of their initial goals and have already brought a significant contribution to space exploration.

        The development of the Sanofi Pasteur’s recombinant yellow fever-17D–dengue virus, live, attenuated, tetravalent dengue vaccine (TDV), often referred to as the CYD dengue vaccine or CYD-TDV, presents many similarities with the long-standing effort represented by the European Rosetta project, having started at the same time in the mid-90s, required a similar investment, and mobilized similar numbers of collaborators from multigeopgraphic and multidisciplinary teams, within and outside the company, and for which success could only be established at the end of development. While it still represents a large effort necessitating the acquisition of data in pivotal efficacy trials, the present review aims to summarize the different steps of this vaccine’s development, focusing on the clinical data acquired in the last four years from three efficacy trials—one proof-of-concept phase IIb and two pivotal phase III efficacy trials. It will thus update the previous reviews published in Vaccine in 2010 and 2011 [1,2]…

        ..As part of the clinical development of the vaccine, three efficacy trials were undertaken, the results from which have been published in the past two years. These included a proof-of-concept phase IIb efficacy trial in Thailand [3], and two pivotal phase III efficacy trials in Asia [4] and Latin America [5]. Indeed, the first priority was to develop the vaccine in endemic countries of Asia-Pacific, Latin America, and the Caribbean to address the unmet medical need in these regions…

        • http://www.sanofipasteur.com/en/articles/theworld-s-first-large-scale-dengue-vaccine-efficacy-study-successfully-achieved-its-primary-clinical-endpoint.aspx

          Lyon, France, – April 28, 2014 – Sanofi Pasteur, the vaccines division of Sanofi (EURONEXT: SAN and NYSE: SNY), today announced that the first of two pivotal Phase III efficacy studies with its dengue vaccine candidate has achieved its primary clinical endpoint. The efficacy study showed a significant reduction of 56% of dengue disease cases. Initial safety data are consistent with the good safety profile observed in previous studies. Full analysis of the data will be undertaken in the coming weeks and reviewed by external experts prior to disclosure at an upcoming international scientific congress and publication in a peer-reviewed journal later this year.

          https://www.thestar.com.my/news/nation/2014/07/11/dengue-vaccine-trial-shows-promise-french-firm-believes-88-of-haemorrhagic-fever-cases-can-be-reduce/ – 11 July 2014

          Lyon, France, – April 28, 2014 – Sanofi Pasteur, the vaccines division of Sanofi (EURONEXT: SAN and NYSE: SNY), today announced that the first of two pivotal Phase III efficacy studies with its dengue vaccine candidate has achieved its primary clinical endpoint. The efficacy study showed a significant reduction of 56% of dengue disease cases. Initial safety data are consistent with the good safety profile observed in previous studies. Full analysis of the data will be undertaken in the coming weeks and reviewed by external experts prior to disclosure at an upcoming international scientific congress and publication in a peer-reviewed journal later this year.

          https://www.nytimes.com/2014/04/29/business/international/sanofi-says-dengue-vaccine-succeeds-in-late-stage-trial.html April 28, 2014

          The French pharmaceutical company Sanofi said on Monday that its experimental vaccine for dengue fever had succeeded in its first late-stage clinical trial. The results could help pave the way for the introduction of the first vaccine to prevent a disease that afflicts an estimated 50 million to 100 million people a year.

          Sanofi said the vaccine reduced the incidence of dengue fever by 56 percent in a trial involving more than 10,000 children in Southeast Asia.

          Outside experts said they were hoping for even greater effectiveness, but some said the vaccine could still be useful..

          ..A spokesman for Sanofi said that since there was no vaccine now, Sanofi’s product might be welcomed by many countries and help many people. “Fifty-six percent has to be compared to zero today,” said the spokesman, Alain Bernal.

          He said the company would discuss possible licensing of the vaccine after seeing the results from a second Phase 3 trial, this one in Latin America, in the third quarter.

          https://www.asianscientist.com/2015/06/features/dengue-day-2015-interview-dr-joselito-sta-ana/

          ..Sanofi Pasteur has completed the active phase of the two large Phase III clinical studies in Asia and Latin America with results already published in 2014. We are currently in regulatory approval process for the authority to evaluate the data comprehensively. Sanofi Pasteur’s objective with its dengue vaccine is to have a significant impact on public health in endemic countries but the decision to use the vaccine will be made by the country themselves and not by Sanofi Pasteur..

          ..In 2009, prior to Phase III results, Sanofi Pasteur built a dedicated production facility for the dengue vaccine in order to secure adequate supply of quality product in a timely manner to countries upon approval. This facility will have a production capacity of 100 million doses per year from 2016, this means one billion doses in ten years..

          https://www.rappler.com/business/economy-watch/114680-aquino-eu-firms-business-ph – Dec. 2, 2015

          Aquino also had a business meeting with officials of Sanofi Pasteur for the introduction of a dengue vaccine in the Philippines, as the French pharmaceutical company moves toward completing the clinical trials for the vaccine. (READ: Soon: Vaccine from France to help fight dengue in PH)

          Sanofi launched 25 clinical studies (20 completed, 5 ongoing) involving over 40,000 subjects. These are being conducted in 15 dengue-endemic and non-endemic countries, including the Philippines. Here, all 3 research phases were conducted.

          For the possible introduction of the dengue vaccine in the Philippines, the Department of Health is formulating policies and guidelines in cooperation with the private sector. Vaccine registration by the Philippine Food and Drug Administration (FDA) is underway and is expected to be completed soon.

          https://www.asianscientist.com/2012/07/pharma/sanofi-pasteur-dengue-vaccine-thailand-efficacy-trial-2012/

          AsianScientist (Jul. 27, 2012) – Sanofi Pasteur, the vaccines division of Sanofi, announced on Thursday promising efficacy results of its dengue vaccine candidate in an efficacy trial conducted in Thailand. The study was conducted in 4,002 children aged 4 to 11 years, in partnership with the Mahidol University under the patronage of the Thai Ministry of Public Health in Muang district of the Ratchaburi Province. The tetravalent dengue vaccine candidate is a live attenuated vaccine, administered in a vaccination schedule of three doses given six months apart (at 0, 6, and 12 months). Evidence of protection was demonstrated against three of the four virus serotypes circulating in Thailand. Analyses are ongoing to understand the lack of protection for the fourth serotype in the particular epidemiological context of Thailand. Importantly, the results confirm the excellent safety profile of the vaccine candidate. The full data resulting from this first efficacy trial are currently under scientific review, and will be published later this year.

          http://www.philstar.com/headlines/2014/06/15/1334942/doh-agency-says-devt-dengue-vaccine-promising

          According to Rosario Capeding, head of the Department of Microbiology of the Research Institute for Tropical Medicine (RITM), their clinical trial for vaccine development has shown a 56-percent reduction of the disease.

          An agency under the Department of Health, the RITM is doing the independent trials for Sanofi Pasteur, the vaccines division of Sanofi, in San Pablo City in Laguna and Cebu City.
          A total of 2,567 children aged two to 14 are covered by the trials in San Pablo City and more than 900 others in Cebu City. The RITM started vaccinating them against dengue in June 2011 with three doses of vaccines at an interval of six months.

          “The results are promising. It is important to have a vaccine against dengue but, at the same time, we should not set aside the primary control measure against dengue, which is vector control,” Capeding told The STAR at the sidelines of the ASEAN Dengue Summit being hosted by the Philippines here.

          She noted that there are five other pharmaceutical companies doing clinical trials for dengue vaccines, but only Sanofi has reached phase three, the last phase of clinical development before the product is licensed and released to the market.

          http://www.gmanetwork.com/news/news/nation/505906/dengue-vaccine-for-fda-approval-within-this-year-doh/story/

          A vaccine against dengue is being readied for registration with the Philippines’ Food and Drug Administration within the year, health officials said on Wednesday. With the new vaccine, the Department of Health could soon hasten plans for its rollout within months after FDA approval.

          “The results are promising and hopefully matapos ang registration nila within the year, para mapagplanuhan na ang paggamit,” DOH spokesperson Dr. Lyndon Lee Suy said in an interview with GMA News.

          In the first five months of this year, there have been 25,616 cases of dengue in the country, up by about 10 percent from the same period last year, according to latest available DOH data.

          It took 20 years to develop and test the new vaccine, according to the GMA News report on late evening newscast, “Saksi”.

          In an interview with GMA News Online in October 2014, Dr. Rosario Capeding, head of the dengue study group of the Department of Health’s Research Institute for Tropical Medicine, said the potential anti-dengue vaccine being developed by French firm Sanofi Pasteur seemed to be “safe.”

          http://newsinfo.inquirer.net/620019/anti-dengue-vaccine-developed-available-july-2015

          Health Secretary Enrique Ona announced that a dengue vaccine that underwent clinical trial for more than two years has been successfully tested, showing a promising overall efficacy of 56.6 percent.
          This means that the country might be able to reduce the number of dengue cases in the country by half with the help of the vaccine, Ona said.

          • http://business.inquirer.net/174925/first-dengue-vaccine-out-by-july-next-year

            Following the completion of trials that found its efficacy at 56 percent, the first safe and effective dengue vaccine in the world could be out commercially in the country by July next year…

            Health Secretary Enrique Ona said the vaccine, once approved, should significantly contribute to achieving the World Health Organization’s global strategy for dengue prevention and control by reducing mortality by 50 percent and reducing morbidity by 25 percent by 2020.
            In Asia, the Philippines is among the most affected, with an estimated 166,107 cases reported annually. Moreover, dengue infection is the leading cause of childhood hospitalizations, 36 percent of which afflicts Filipinos between one to nine years old.

            https://www.sciencedirect.com/science/article/pii/S1879437815000042 (2015)

            Immunogenicity and safety of a tetravalent dengue vaccine during a five-year follow-up period
            Capeding et. al

            https://www.reuters.com/article/us-sanofi-dengue/sanofi-dengue-vaccine-promising-but-questions-remain-idUSKBN0FF2OO20140711 – July 11, 2014

            The late-stage trial involved 10,275 healthy children aged 2-14 across five countries in Asia, a region that accounts for over two-thirds of the mosquito-borne disease’s global burden.

            The study found the vaccine was safe and reduced the most serious cases of haemorrhagic fever by nearly 90 percent. But it offered poor protection to young children – who are most at risk from dengue – and proved notably inefficient in tackling one of the viral disease’s four strains.

            The results suggest the new vaccine acts best as an immune booster for patients with some previous exposure, and therefore may be most useful in tropical regions where dengue is common, rather than as a vaccination for travellers.

            http://www.bbc.com/news/health-28243587

            In the largest late-stage trial of a vaccine to date, researchers from five centres across Asia treated 6,000 children aged between two and 14 years old.
            Some 56% were seen to have protection against the virus at the end of two years.
            It worked best for children with certain subtypes of the virus and those who had been exposed to it before.
            And the vaccine had an even greater impact on severe forms of the disease, reducing the number of people needing treatment in hospital and preventing 80% of cases of haemorrhagic fever – a potentially life-threatening complication.
            Lead author Dr Maria Rosario Capeding, from the Research Institute for Tropical Medicine in the Philippines, told the BBC: “Given that dengue is a major public health problem in most Asian countries the findings have the potential to have a huge impact on public health.

            http://www.asiaone.com/health/disarming-dengue

            He was confirmed to have dengue type 3.

            But when Juhani’s high fever lasted for more than a week than the average four to five days, and his platelet counts dropped, Dr Capeding was fearful and apprehensive that he might have potentially fatal bleeding.

            “I know that dengue can simply be managed by fluid replacement and this is easy for me to say during my lectures to physicians. I realised that the reality is different, especially when it is your child who is sick,” says Dr Capeding.

            Dr Capeding’s story may not be typical (how many of the estimated 220 million people infected with the dengue virus every year have relatives who are doctors or dengue researchers?) but it contains many lessons about dengue prevention and treatment.

            Without a working vaccine, we cannot actually protect ourselves from dengue.

            The best way to decrease the risk of getting infected is to reduce our chances of getting bitten by a mosquito by destroying mosquito-breeding sites.

            And without specific treatment, doctors can only manage their patients’ symptoms and help their patients stay strong enough to fight the virus from within.

            But most of all, Dr Capeding’s story highlighted the emotional cost that comes with dengue.

            Although she knew that a dengue vaccine is still years away, she couldn’t help but wish it was available earlier..

            ..However, since October last year, the company’s candidate vaccine is the first to enter phase III clinical trials, the last scientific hurdle for the vaccine to prove its worth before health regulatory bodies can decide to approve its use in their respective countries.

            These trials are currently ongoing in six countries from South East Asia (including Malaysia), six from Latin America, the United States, and Australia.

            The vaccine is (simplistically) a concoction of four different, weakened, viruses that each contain a DNA backbone of a Yellow Fever virus that is inserted with a gene that codes for the membrane and envelope of one of the four dengue viruses.

            “So far, there is promising data … and we are hopefully optimistic,” says Lang.

            Published results from Phase I studies funded by Sanofi Pasteur, one in the US and another in the Philippines, have suggested that the vaccine is safe and able to elicit an immune response from almost all adult participants and more than 80% in children and adolescents when given in three doses within a year respectively.

            Phase II results from an efficacy study in Thailand is expected to be available by the end of year 2012..

          • https://mrcdata.dide.ic.ac.uk/_dengue/dengue.php

            The maps show estimates of seroprevalence and are for illustrative purposes. They should not be used as a standalone decision making tool.

            http://pps.org.ph/wp-content/uploads/2017/04/Serological-Testing.pdf

            There is currently no national data documenting dengue seroprevalence in the Philippines. However, in one study involving 1,066 Filipino children aged 2-16 years, dengue seropositivity rates as determined by plaque-reduction sero-neutralization assay were found to increase with increasing age: 58% in those age 2-4 years, 74.9% in those 5-8 years, 88.5% in those 9-12 years, and 93% in those 13-16 years. Subsequently, a prospective longitudinal cohort study conducted in Cebu City among 1,008 children and adults starting from age 6 months and older showed that >98.3% of all those > 15 years developed evidence of multi-typic dengue HAI antibodies during the 12-month study period. However, only 17.5% of dengue infections that occurred were symptomatic; 82.5% developed subclinical infection.10

            In the absence of population-based serologic data, the WHO suggests the use of epidemiologic information (incidence, morbidity and mortality rate among infectious diseases) as an indicator.

            http://agris.fao.org/agris-search/search.do?recordID=US201500139095

            Live-attenuated, tetravalent dengue vaccine in children, adolescents and adults in a dengue endemic country: Randomized controlled phase I trial in the Philippines [2011]

            Capeding, Rosario Z. Luna, Imelda A. Bomasang, Emily Lupisan, Socorro et al.

          • http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004337
            ..The study was conducted in the barangay (i.e., village equivalent) of Punta Princesa, an urban community in Cebu City, capital of Cebu province located within the Visayas region of the Philippines. Punta Princesa encompasses 0.96 sq km with a total population of about 27,000 people. Public outpatient care is available to local residents at the Punta Princesa Health Center with patients who require higher level medical care or hospitalization referred to Cebu City Medical Center, the tertiary public hospital of Cebu City, or to VSMMC, the tertiary public hospital of Cebu province..

            ..Enrolled subjects underwent active community-based surveillance to detect acute febrile illness which was defined as reported fever or measured temperature >38.0°C. Subjects were instructed to report any fevers, and were contacted by study staff once a week through telephone, short message service, and/or home visits. A history of fever within the prior seven days triggered an acute fever investigation consisting of an acute illness visit followed by subsequent visits at 2, 5 and 8 days, and a convalescent visit at 3 weeks. Clinical assessments were performed at all visits, and blood was collected at the acute and 3-week convalescent visits. Blood was processed into serum aliquots within 24 hours of phlebotomy, frozen at approximately -70°C and shipped on dry ice to AFRIMS in Bangkok, Thailand. Acute serum was tested by hemi-nested reverse transcriptase polymerase chain reaction (PCR) to detect DENV RNA. Paired acute/convalescent sera were tested by an in-house DENV IgM/IgG capture enzyme-linked immunosorbent assay (ELISA) and by DENV/JEV HAI..

            https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222740/

            ..Few studies show any analysis of the seroepidemiology of dengue. Nevertheless, a longitudinal prospective cohort study of fever in 4441 infants in San Pablo Laguna conducted from January 2007 to May 2009, showed that 11% of all presenting undifferentiated febrile illness was dengue (40 cases of dengue diagnosed out of 353 cases of fever). All cases of dengue but one were primary dengue (as determined using IgG/IgM and paired sera) and DHF was seen only in infants under 8 months of age. DENV-3 predominated in this cohort (as noted below) and infants with high levels of anti-dengue 3 antibodies at birth developed dengue infections later than infants with low levels of antibody at birth. The overall infection rate (as determined by seroconversion in a subset of this cohort) was nearly 12%, between January 2007 and January 2008, and 87% of these dengue infections were asymptomatic or only mildly symptomatic [44], [46] (Table S1). In a prospective study of children admitted with fever without a clear focus to St Lukes Medical Centre in Quezon City, Metro Manila, from January 1999 to December 2001, 71.4% had dengue (confirmed by IgM and/or RT-PCR) and 1/3 had DHF [47], [48]. Furthermore, in another prospective fever surveillance study of patients with a mean age of 18 years admitted to San Lazaro Hospital, in Manila, Luzon, 87% of those with fever without a clear focus of infection had dengue, 7% of the cases were primary dengue infections (determined by IgM/IgG ELISA) [43]..

            ..Studies published during the review period that observed DENV serotypes were hospital or community based and involved low numbers of cases; no published studies examined national or regional serotype distribution. All four DENV serotypes were reportedly present in the Philippines at some time during the review period ( Figure 4 ) [43]–[50]. DENV-1 and -2 appeared to be more prevalent (2000–2001) in a prospective study of hospitalized paediatric patients in NCR (January 1999 to December 2001) [47], [48] and in isolates from dengue disease outbreaks in the Philippines (1995–2002) [50]. In studies towards the end of the review period DENV-3 became more predominant [43]–[46], [49], DENV-4 was either not present [44], [46]–[48], [50], or was present in up to 7% of the dengue disease cases [45], [49], [50] in the studies included in this review..

            http://www.doh.gov.ph/sites/default/files/statistics/DENGUE%20MW28.pdf

            A total of 66,299 suspect dengue cases were reported nationwide from January 1 to July 16, 2016.
            This is 22.9% higher compared to the same time period last year (53,938).

            Most of the cases were from the following regions: Region IV-A (12.2%), Region VII & X (9.7%),
            Region III & XII (9.1%), Region XI (7.6%) and Region VI (7.2%).

            http://www.gmanetwork.com/news/news/nation/223701/philippines-ranks-4th-in-asean-wide-dengue-incidence/story/ – June 17, 2011

            The Philippines ranks 4th in the list of Association of Southeast Asian Nations (ASEAN) member-countries tormented by dengue, health experts announced this week, prompting calls for concerted efforts in preventing the spread of the potentially fatal ailment.

            The 10-member bloc launched the first ASEAN-wide Dengue Day in Jakarta on June 15 to call for a region-wide action in combating dengue, “one of the most neglected tropical diseases in the world,” Philippine dengue expert Dr. Lyndon Lee Suy said.

            The ASEAN grouping has the highest number of dengue infections in the Asia-Pacific region, which in turn carries 75 percent of the global dengue disease burden, Filipino and international dengue experts said.

            Lee Suy, national program coordinator of the Department of Health (DOH) for dengue prevention and control, said Lao PDR recorded the highest incidence of dengue in the region in 2010 followed by Malaysia, Vietnam, and the Philippines.

            Thailand ranked fifth followed by Cambodia, Indonesia, and Myanmar. No data was available for Brunei and Singapore, he said. It is the first time for comparative dengue statistics in the ASEAN region to be released.

            http://www.philstar.com/opinion/2017/12/11/1767239/past-dengue-probe-headed-nowhere

            Over a year ago, Nov. 18, 2016, five doctors and health activists asked the House of Reps committee on health to stop the vaccinations. Their reasons were clear in the position paper:

            “Alarmed by a DOH program to vaccinate one million children against dengue virus, amidst questions about cost-effectiveness, safety and ethics, we the undersigned individuals hereby declare that:…

            “In view of all these problems, and in the interest of public safety, we strongly recommend that the DOH dengue vaccination program be suspended, pending completion of results of ongoing studies.

            “Signed: Antonio L. Dans, MD, MSc, Academician, National Academy of Science and Technology;

            “Leonila F. Dans, MD, MSc, Professor, University of the Philippines College of Medicine;

            “Anthony Leachon, MD, Independent Director, Philhealth (Representative of the Monetary Board);

            “Ana Maria R. Nemenzo, WomanHealth;

            “Mercedes Fabros, Chairperson, Alternative Budget Initiative”

            The five were special invitees to the committee hearing that day. On agenda was precisely their four objections to Dengvaxia. Yet they suddenly were disallowed from speaking. A last-minute guest, former health secretary Janette Garin who had purchased the vaccines, instead dominated the discussions. Why did that happen?
            Well never know, won’t we?

        • http://cnnphilippines.com/news/2017/12/09/The-Dengvaxia-controversy.html

          2014
          Dengvaxia successfully completes its two parallel Phase 3 clinical studies, which compare the safety and effectiveness of the new treatment.

          The Philippines was among the 10 countries that took part in the study.

          November 9, 2014
          Then-President Benigno Aquino III meets Sanofi Senior Vice President in Asia Region Jean-Luc Lowinski at the Philippine Embassy in Beijing, China.

          June 9, 2015
          Then-Health Secretary Janette Garin negotiates with Sanofi to reduce the cost of buying the vaccines.

          October 29, 2015
          Sanofi Pasteur applies at the DOH for Dengvaxia to be included in the Philippine National Formulary, a list of drugs that all pharmacies in the Philippines must carry, pending approval by the Food and Drug Administration (FDA).

          December 1, 2015
          Aquino and Garin meet Sanofi officials during the UN Conference on Climate Change in Paris, France.

          December 10, 2015
          Garin submits a proposal to the Budget Department to buy three million doses of Dengvaxia.

          December 22, 2015
          The Philippines grants marketing approval to Dengvaxia, making it the first vaccine to be licensed for the prevention of dengue in Asia.

          The Food and Drug Administration (FDA) approves the drug for the prevention of disease caused by all four dengue types in individuals from nine to 45 years old living in high-risk areas.

          December 28, 2015
          The DOH-Family Health Office submits a request to Garin to exempt Dengvaxia from being included in the Philippine National Formulary. This excludes it from review by the Formulary Executive Council (FEC), which determines what drugs are included on the list.

          December 29, 2015
          The Budget Department issues a ₱3.5-billion Special Allotment Release Order to Garin’s office to purchase the vaccines.

          January 21, 2016
          The Philippine Children’s Medical Center (PCMC) makes a ₱3-billion purchase order for the vaccines without approval from the FEC.

          February 3, 2016
          Garin issues a Certificate of Exemption for Dengvaxia vaccines to be utilized in the pilot implementation in the National Capital Region, Region III, and Region IV-A.

          February 11, 2016
          The Philippines, under Health Secretary Janette Garin, hosts the worldwide launch of Dengvaxia.

          Read: World’s first dengue vaccine now available in PH

          March 2016
          The World Health Organization (WHO) releases a paper saying Dengvaxia “may be ineffective or may even increase that risk in those who are seronegative at the time of first vaccination.”

          Seronegative pertains to people who have not yet had dengue.

          The WHO calls for more studies into the vaccine.

          March 8, 2016
          Garin issues a ₱3-billion disbursement voucher to the PCMC to fund the purchase of the vaccines.

          March 9, 2016
          The PCMC issues its purchase order to Zuellig Pharma, the distributor of Dengvaxia.

          April 4, 2016
          The government kicks off its ₱3.5-billion, school-based dengue immunization program. The health department says students would be given three doses, which would be administered every six months.

          Read: DOH starts dengue vaccination program

          July 2016
          The WHO releases another paper, saying Dengvaxia “may act as a silent natural infection that primes seronegative vaccinees to experience a secondary-like infection upon their first exposure to dengue virus.”

          In other words, the body says the vaccine “may be ineffective or may theoretically even increase the future risk of hospitalized or severe dengue illness in those who are seronegative at the time of first vaccination regardless of age.”

          That same month, former Health Secretary Paulyn Ubial issues a Resolution temporarily suspending the school-based dengue immunization program.

          Only the 489,003 pupils who received the first dose would take the second and third doses.

          September 2016
          The health department moves to continue the vaccination program.

          That same month, the Medical Research Council Center FOR Outbreak Analysis and Modelling at Imperial College London releases a study saying Dengvaxia could lead to an increase in the number of cases of the disease if not implemented correctly.

          Read: New dengue vaccine could instead cause more cases, experts warn

          “Unlike most diseases, the second time you get dengue, it’s much more likely to be severe than the first time you get it,” said the center’s director Neil Ferguson.

          October 2016
          The Singapore Health Sciences Authority flags “postulated risk” of Dengvaxia.

          “As the vaccine is more effective in those who had previous dengue infection, and that there is a postulated risk of severe dengue in those who do not have past dengue infections when they become infected,” it said.

          November 2016
          The House of Representatives probes the allegedly anomalous purchase of the Dengvaxia vaccines.

          Its draft report of the Committee on Health, the DOH reported there were 30 cases from March 18 to August 20, 2016 that were “considered as serious cases that needed hospitalization.”

          Of the three deaths it monitored, two were not related to the immunization program.

          The panel directed the DOH to check the medical records of Christine de Guzman who died months after taking the vaccine.

          It also recommended that the DOH temporarily suspend the expansion of the vaccination program, pending completion of data collection, evaluation, and analyses on “adverse effects.”

          Related: House body resumes probe of school-based dengue vaccine program

          December 2016
          The Senate launches its own investigation into the vaccines, saying the project cost was too big and was approved without congressional approval.

          Read: Senate probes dengue vaccine program

          November 29, 2017
          Sanofi Pasteur announces the results of new clinical data analysis, which found that Dengvaxia is more risky for people not previously infected by the virus.

          Read: Drug firm warns of ‘severe disease’ from dengue vaccine for people with no prior infection

          “For those not previously infected by dengue virus, however, the analysis found that in the longer term, more cases of severe disease could occur following vaccination upon a subsequent dengue infection,” it said.

          “For individuals who have not been previously infected by dengue virus, vaccination should not be recommended,” it added.

          December 1, 2017
          Following Sanofi Pasteur’s announcement, Health Secretary Francisco Duque III orders the temporary suspension of the dengue vaccination program.

          Read: Gov’t halts dengue vaccination program due to health risk

          Duque says 733,713 children from Central Luzon, the region of Cavite, Laguna, Batangas, Rizal, and Quezon, and Metro Manila were administered Dengvaxia. Eight to 10 percent or about 70,000 children have not had dengue yet, the DOH added.

          December 4, 2017
          The Justice Department orders the National Bureau of Investigation to look into the dengue vaccination program.

          Read: DOJ orders probe of dengue vaccine program

          December 5, 2017
          The FDA suspends the sale and distribution of Dengvaxia.

          Read: FDA suspends sale, distribution of dengue vaccine Dengvaxia

          The WHO says it never recommended to countries the use Dengvaxia in their national immunization programs.

          Read: WHO denies recommending Dengvaxia for nat’l immunization programs

          December 6, 2017
          The health department says more than 800,000 students received the vaccine, up from the 733,713 figure mentioned by Duque.

          It is now monitoring 40 cases of children who fell seriously ill, up from 30 in 2016, and nine deaths.

          Read: DOH: More than 800,000 children vaccinated with Dengvaxia

          December 7, 2017
          The Health Department says it will return around 800,000 leftover Dengvaxia vaccines, worth P1.4-billion, to Sanofi.

          Read: Health Department to return ₱1.4 billion worth of Dengvaxia vaccines

          December 8, 2017
          The health department calls for a refund of the P3.5 billion it paid for the vaccines, adding it has created a task force to look into the program.

          Read: DOH to demand from Sanofi full refund of P3.5 billion spent on Dengvaxia

          That same day, the House and the Senate announce they will again investigate the dengue vaccination program. It begins on Monday, December 11.

          Read: Senate to open probe on dengue vaccine scare

          December 11, 2017
          The Senate starts its probe into the Dengvaxia issue. Former Health Secretaries Janette Garin and Paulyn Ubial, as well as Health Secretary Francisco Duque III and Sanofi officials, are among those present.

          Before the start of the hearing, former Health Secretary Enrique said Garin, his successor, was “solely responsible” for the Dengvaxia issue.

          Read: Ex-DOH Sec. Ona: Garin solely responsible for Dengvaxia ‘nightmare’

          Meanwhile, Garin says the purchase of the vaccines was “above board.”

          Read: Ex-DOH Secretary Garin: No corruption in Dengvaxia purchase

          This is a developing story. Please refresh the page for updates.

          http://www.healthmap.org/site/diseasedaily/article/dengue-vaccine-candidate-falls-short-clinical-trial-91412 (Phase 2 trial) Sep. 4, 2012

          The vaccine developed by Sanofi Pasteur was only about 30 percent effective in preventing dengue fever during a randomized, controlled trial in Thailand – well below the 70 percent researchers had been expecting. While disappointing, the results were not totally deflating.

          Roughly 4,000 schoolchildren ages 4 to 11 were included in the study in the Muang district, about 100 kilometers (62 miles) west of Bangkok. Of those, 2,452 of them received three doses of the vaccine. Researchers followed students for two years, and took blood samples any time the children fell ill with a fever. The samples were tested to confirm dengue and to identify the dengue virus serotype.

          https://www.nytimes.com/2014/04/29/business/international/sanofi-says-dengue-vaccine-succeeds-in-late-stage-trial.html

          The French pharmaceutical company Sanofi said on Monday that its experimental vaccine for dengue fever had succeeded in its first late-stage clinical trial. The results could help pave the way for the introduction of the first vaccine to prevent a disease that afflicts an estimated 50 million to 100 million people a year.

          Sanofi said the vaccine reduced the incidence of dengue fever by 56 percent in a trial involving more than 10,000 children in Southeast Asia.

          Outside experts said they were hoping for even greater effectiveness, but some said the vaccine could still be useful.

          “I’m looking for something that could potentially do better than this,” said Dr. Robert Edelman, clinical professor of medicine and pediatrics at the University of Maryland. He said ideally a vaccine would be 80 percent effective, which would not only protect vaccinated individuals but also reduce transmission to unvaccinated people.

          But Duane J. Gubler, a dengue expert at the Duke-NUS Graduate School of Medicine in Singapore, called the results “very encouraging.”

          http://www.sanofipasteur.com/en/articles/sanofi-pasteur-s-dengue-vaccine-candidate-successfully-completes-final-landmark-phase-3-clinical-efficacy-study-in-latin-america.aspx

          Lyon, France – 3rd September, 2014 – Sanofi Pasteur, the vaccines division of Sanofi (EURONEXT: SAN and NYSE: SNY), today announced that the final landmark phase III efficacy study of its dengue vaccine candidate in Latin America successfully achieved its primary clinical endpoint. Results showed an overall significant reduction of 60.8 percent* of dengue disease cases in children and adolescents 9-16 years old after a three-dose vaccination schedule. Importantly, efficacy was observed against each of the four dengue serotypes.*

          https://www.reuters.com/article/us-sanofi-dengue/final-trial-confirms-efficacy-of-sanofis-dengue-vaccine-idUSKBN0GY0C520140903

          PARIS (Reuters) – French drugmaker Sanofi, developing the first vaccine against dengue fever, said its product reduced disease cases by 60.8 percent in a large final clinical trial.

          Sanofi has invested more than 1.3 billion euros ($1.7 billion) in the project, undertaking two decades of research on the world’s fastest-growing tropical disease.

          The final study – conducted on 20,875 children aged 9-16 across five countries in Latin America – confirmed that the vaccine was safe, provided high protection against dengue hemorrhagic fever and cut by 80 percent the risk of hospitalization, the Paris-based company said on Wednesday.

          It was 42.3 percent efficient in tackling serotype 2, one of the viral disease’s four strains, compared to 35 percent in a previous Asian trial on some 10,000 children, a relatively weak rate that has puzzled scientists. [ID:nL6N0PM1OV]

          Overall, the findings were consistent and more reliable in the Latin American trial as it had twice as many patients as the Asian trial, said Nicholas Jackson, head of dengue research and development at Sanofi’s vaccines unit Sanofi Pasteur.

          “We’re talking about different regions, different seasons, different demographics, and it’s very important for a vaccine to perform consistently, so these results are extremely pleasing,” he told Reuters in an interview.

          https://www.omicsonline.org/safety-and-immunogenicity-of-recombinant-live-attenuated-tetravalent-dengue-vaccine-cyd-tdv-in-healthy-vietnamese-adults-and-children-2157-7560.1000162.php?aid=10250 – Oct. 5, 2012

          Participants were kept under observation for 30 minutes after each vaccination and were followed-up for safety until 6 months after the last vaccination. Participants or parents were provided with a thermometer, a ruler and a diary card to record any adverse event (AE) following each vaccination. The following AEs were documented and graded using a pre- defined severity scale as reported elsewhere solicited injection site reactions within 7 days (i.e., pain, erythema and swelling), solicited systemic reactions within 14 days (i.e., fever, headache, malaise, myalgia, and asthenia) and unsolicited AEs up to 28 days after each vaccination. All serious adverse events (SAE) were documented up to 6 months after the last vaccination.

          http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0036-46652012000700007

          The first phase III study was initiated in 2010 in Australia to evaluate lot-to-lot consistency. The first efficacy study, including 4,000 children (4-11 years) is ongoing in a highly endemic area of Thailand, and the results are expected for the end of 2012. Positive results from this study, conducted in an area where the force of infection is high would represent the first time clinical efficacy has been demonstrated with a dengue vaccine, and would allow us to consider initial submission to the regulatory authorities in some countries8.

          To expand the efficacy database in different countries, two other phase III efficacy studies are ongoing in Asia (Thailand, Indonesia, Malaysia, Viet Nan, Philippines), with planned inclusion of about 10,000 children (2-14 years) and Latin America (Colombia, Mexico, Honduras, Porto Rico and Brazil) where the number of enrolled children aged 9-16 years is expected to be 20,000.

          https://www.kff.org/news-summary/clinical-trial-results-signal-promise-unresolved-challenges-in-finding-effective-dengue-vaccine/ – Oct. 2012

          The first-ever results from a dengue virus vaccine clinical trial aimed at showing effectiveness “provide signals rather than definitive answers, and a mixture of both promise and unresolved challenges,” Orin Levine, executive director of the International Vaccine Access Center, and Ciro de Quadros, executive vice president of the Sabin Vaccine Institute, write in the Huffington Post “Impact” blog. “To date, these represent the most promising indications that a safe, effective vaccine to prevent dengue is technically feasible,” they continue, adding, “At the same time, the results on protection were inconclusive, somewhat inconsistent with the measured immune responses and uneven across the four strains included in the vaccine.”

          “Fortunately, a much larger trial already underway in 10 different countries is likely to tell us by 2014 if the signals observed in this trial are accurate or not,” Levine and de Quadros note, saying “[i]t will be important to see the results of the larger trial and the effectiveness of the vaccine in different epidemiological settings.” They continue, “We at the Dengue Vaccine Initiative (DVI) will continue to follow the progress of Sanofi’s vaccine as we work to lay the foundations for the adoption and rollout of a licensed dengue vaccine in the future,” concluding, “In the meantime, the dengue virus better look out. A safe, effective vaccine might be right on its tail and about to overtake it” (9/12). Sep. 3, 2012

          http://symbiosisonlinepublishing.blogspot.de/2014/05/promising-outcome-from-cyd-tdv-dengue.html – 27 May 2014

          In the absence of a particular therapy, WHO, in collaboration with other partners; has initiated vaccine research program (IVR, Initiative for vaccine research) for developing a dengue vaccine. Several vaccine candidates are at the pre-clinical and clinical trials.

          The most promising one is the vaccine being developed by Sanofi Pasteur. The CYD-TDV Dengue Vaccine is a tetravalent vaccine that contains live, attenuated, chimeric yellow fever- dengue virus. The phase III clinical trials for this vaccine have shown good results. It can be the vaccine to look for!

      • http://www.gmanetwork.com/news/news/nation/636522/noynoy-s-statement/story/

        Former President Benigno Aquino III on Thursday defended his government’s decision to purchase the now controversial anti-dengue vaccine Dengvaxia.

        Read the full text of the statement read by the former chief executive during the Senate blue ribbon committee probe on the P3.5-billion program.

        https://www.rappler.com/nation/190965-senate-hearing-dengvaxia-dengue-vaccine

        MANILA, Philippines – The Senate is investigating the controversy surrounding the purchase of P3.5 billion worth of dengue vaccine doses for public school students in the country.

        New analysis of clinical data showed Sanofi Pasteur’s Dengvaxia poses more risks for people who have not been infected by the virus before immunization.

        More than 700,000 Filipino children in Luzon have been given the dengue vaccine under the government’s immunization program, according to the Department of Health (DOH).

        http://www.gmanetwork.com/news/news/nation/636551/noynoy-refutes-rushed-purchase-of-dengvaxia-vaccine/story/

        Some Sanofi officials met with Aquino on December 1, 2015 when Aqiuno visited Paris for the UN Conference on Climate Change.

        On December 10,2015, then-Health Secretary Janette Garin submitted a proposal to the Department of Budget and Management (DBM) for health facilities enhancement program (HFEP) funding and procurement of dengue vaccines.

        On December 21, a meeting was held regarding the declaration of savings to augment items of appropriations for various urgent projects. A day later, the FDA approved the marketing of Dengvaxia.

        By December 23, a memorandum was issued by Abad to fund projects from the Miscellaneous Personnel Benefits Fund (MPBF) and Pension Gratuity Fund (PGF) savings. Among the projects indentified was the dengue vaccination program.

        On December 29, a Special Allotment Release Order (SARO) was issued by the DBM to the DOH, obligating P3.5 billion for the vaccination program.

        Aquino explained that savings had to be used so that they can purchase the vaccines already.

        “The end result if that if you do not do this at this point in time, you are practically saying that the first implementation of this vaccine will be in 2017 because it will be for the next budget cycle, which will be under the new administration,” he said. Even then, Aquino added that there was no guarantee the vaccines will be administered considering a “learning curve” at the start of every presidency.

        • https://www.rappler.com/nation/191348-congress-pressured-ubial-dengue-vaccination-program

          According to Ubial, she was very vocal against the proposal to include the dengue vaccine in the national immunization program even while she was Garin’s assistant secretary.

          She said before she became DOH chief, 489,003 children have been vaccinated already.

          In her statement, Ubial mentioned the Formulary Executive Council (FEC), which warned against the widespread use of Sanofi Pasteur’s Dengvaxia and instead only recommended its “phased” implementation and “staged” procurement. The FEC is a panel of top Filipino experts that determines which drugs the government may procure and use.

          “I was very sad to tell the group that I wanted to stick to the first decision of the expert panel that only those who were given the first dose will continue the other doses. After which, we will stop the implementation… look at the data, and decide how to move forward,” said Ubial.

          On July 18, 2016, Ubial signed a resolution recommending the deferment of the program, saying the vaccine is not proven safe. She was criticized for this, however, during the budget hearing at the House of Representatives.

          “But during the budget hearing, there was a lot of pressure in Congress to expand it to other parts of the country with higher [cases] of dengue, which is Region 7. I didn’t give in to the pressure of Congress. I told them I cannot expand to other areas because the recommendation of the expert panel,” she narrated.

          “But I was pushed [and asked], ‘Why can’t you have a 2nd opinion?’” added Ubial.

          She then convened a second panel of experts. But by this time, the World Health Organization (WHO) already published its first position on Dengvaxia.

          WHO said countries should consider the introduction of the dengue vaccine “only in geographic settings (national or subnational) where epidemiological data indicate a high burden of disease.” It also did not recommend the use of the vaccine for children under 9 years of age.

          And so on September 28, 2016, Ubial not only gave the go-signal to continue the dengue vaccination program but even expanded it in Cebu. A total of 123,000 Cebuano kids got the risky vaccine.

          Ubial’s predecessor Garin is the wife of Iloilo 1st District Representative Oscar Garin Jr. Oscar is the older brother of AAMBIS-OWA and House Deputy Speaker Sharon Garin.

          • https://newsinfo.inquirer.net/952347/breaking-news-dengvaxia-dengue-overpricing-grace-poe-senate-hilton-lam-sanofi-pasteur

            https://www.rappler.com/newsbreak/in-depth/190838-mass-use-dengue-vaccine-doh-formulary-executive-council

            MANILA, Philippines – The move to include dengue vaccine Dengvaxia in the national vaccination program did not have the imprimatur of the panel of medical experts that was tasked to review its safety, effectiveness, and even its cost-effectiveness.

            Minutes of a January 25, 2016 meeting of that panel, called the Formulary Executive Council (FEC), said, “Since the safety and efficacy of the vaccine are not yet well-established, the Council suggested a small scale pilot testing of the vaccine through phased implementation rather than vaccinating the target children in the 3 regions all at once.” (READ: W.H.O. didn’t recommend Dengvaxia for PH vaccination program)

            The 3 regions referred to were the National Capital Region, Central Luzon, and Calabarzon (Cavite, Laguna, Batangas, Rizal, Quezon).

            The FEC, according to Executive Order No. 49, is the body mandated to determine which drugs should be part of the National Formulary, a list of drugs that the government can buy and use. Any drug not listed in the formulary cannot be purchased by government.

            Given this restriction, the FEC recommended to the DOH an exemption for Sanofi Pasteur’s Dengvaxia dengue vaccine for only a year, with certain conditions. Any purchases beyond that period were supposed to be subject to another study, according to minutes of meetings obtained by Rappler.

            Under that one-year purchasing period, the FEC also recommended a “staged procurement” of the vaccine.

            All these indicate that then-DOH chief Janette Garin had decided to forego the FEC’s recommendations when she launched the school-based dengue vaccination program in the 3 regions on April 4, 2016. (READ: TIMELINE: Dengue immunization program for public school students)

            http://www.manilatimes.net/congress-scrutinizes-dengue-vaccine-program/300233/ (2016)

            Leachon detailed the timeline of the DOH dengue vaccination program, starting from the meeting between the former president Benigno Aquino III and Sanofi representatives during the Climate Change Summit in Paris on December 2, 2014, then the Food and Drug Administration’s (FDA) approval on December 22, and subsequently the Formulary Executive Council (FEC) defense of the economic study on January 17, 2015.

            This was followed by the signing of the purchase request for two million doses despite the absence or inclusion of the drug in the national drug formulary for the use of public funds on January 21, 2015 and the purchase order made to Zuellig on the same day despite the grant not yet being approved by the Philippine National Drug Formulary (PNDF).

            This was followed by the approval of the budget allotment on January 25, 2015, the approval of the FDA by then-Health Secretary Janette Garin, the actual purchase order on March 9, and the actual purchase and the start of the program last April, despite calls from the scientific community for a more lengthy study first to ensure the safety of the beneficiaries.

            Dr. Antonio Miguel Dans, another health advocate who represented the Philippine College of Physicians (PCP) and National Academy of Science and Technology (NAST), supported the move to suspend the dengue program pending further investigation and until the safety, cost-effectiveness, and preparedness of the recipient students are assured.

            Nela Charade Puno, FDA Executive Director, said that based on their investigation, while the papers are complete, they found what appeared to be a deviation from the usual protocols during the FDA’s approval of the vaccine, under the watch of past officials.

  • https://pr.ricmais.com.br/dia-a-dia/noticias/vacina-contra-a-dengue-podera-custar-ate-r-13463-no-parana-diz-anvisa/

    ..A Agência Nacional de Vigilância Sanitária (Anvisa) definiu, na segunda-feira (25), o preço da dose da vacina da dengue no Brasil. No Paraná, a Dengvaxia poderá custar até R$ 134,63 na rede privada de saúde..

    134.63 BRL = 2,065.01 PHP (per dose of Dengvaxia, according to this Brazilian source)

    • http://www.saude.pr.gov.br/arquivos/File/ManualVacinaDengue03032017.pdf

      ..A Dengue é considerada pelo governo brasileiro como um importante problema de saúde pública. Atualmente as medidas de controle de vetor não têm sido suficientes para a redução do número de casos da doença. Novos casos têm sido notificados no país todo e a maioria dessa população vive em áreas de médio a alto risco para a doença. O Brasil é o primeiro país em número de casos notificados anualmente e somente no ano de 2015, foram registrados 1.649.008 casos prováveis de dengue no país. Entre as semanas epidemiológicas 10 e 17 de 2015, foram notificados mais de 100.000 casos todas as semanas. De acordo com o boletim epidemiológico da semana 52 de 2015, foram confirmados 1.569 casos de dengue grave e 20.329 casos de dengue com sinais de alarme, enquanto no mesmo período de 2014, foram confirmados 764 casos de dengue grave e 8.436 casos de dengue com sinais de alarme. Foram confirmados 863 óbitos por dengue, o que representa um aumento no país de 82,5% em comparação com o mesmo período de 2014, quando foram confirmados 473 óbitos. Entre o grupo de 9 a 45 anos, 1.112.048 casos foram notificados, com 315.233 confirmados laboratorialmente, o que representa que 66% do total de casos em 2015 ocorreram na faixa etária que poderia se beneficiar com a vacina contra dengue (BRASIL, 2016)..

      ..Entre agosto de 2015 e até o dia 19 de julho de 2016, foram notificados no estado do Paraná
      144.936 casos suspeitos de dengue, com 55.260 confirmados, 31.682 por laboratório, sendo 51.583 casos autóctones e 3.677 casos importados. Destes, 62.059 foram descartados (PARANÁ, 2016). Dentre esses casos foram identificados: 751 casos de dengue com sinais de alarme, 92 casos de dengue grave, 61 óbitos confirmados, gerando uma incidência média de 462,09 casos por 100.000 habitantes. É considerada situação de epidemia pelo Ministério da Saúde a incidência igual ou superior a 300 casos por 100.000 habitantes..

  • http://www.gmanetwork.com/news/news/nation/223701/philippines-ranks-4th-in-asean-wide-dengue-incidence/story/ June 7, 2011

    The only way to prevent dengue virus transmission is the removal of the breeding places of disease-carrying mosquitoes, according to Lee Suy of DOH.

    “Vessels containing clear and stagnant water should be emptied regularly. Dengue-carrying mosquitoes lay their larvae in clear and stagnant water such as those found in flower vases, pails, soft drink bottles, cans, and drums,” Lee Suy said.

    • http://www.officialgazette.gov.ph/2014/07/18/dengue-vaccine-successfully-tested-possibly-ready-for-release-july-2015/

      (July 18, 2014) Secretary of Health Enrique T. Ona explained that 56.5% efficacy means that more than half of the subjects did not get dengue compared to the group that did not receive the vaccine.

      The study also showed that after three doses, the vaccine reduced the possibility of a subject developing dengue hemorrhagic fever by 88.5%, according to the World Health Organization (WHO) criteria. Also during the observation period, a 67% reduction in the risk of hospitalization due to dengue was observed.

      Ona added that the study on the dengue vaccine efficacy was performed in five Asian countries, namely Indonesia, Malaysia, Thailand, Vietnam, and the Philippines. The said study involved 10,275 children (2-14 years old). In the Philippines, there were 3,500 children coming from Cebu and San Pablo.

      • http://newsinfo.inquirer.net/237507/dengue-cases-in-philippines-up-by-16 (July 27, 2012)

        Most of the cases centered in Metro Manila with 11,476. This was followed by Calabarzon with 7,265 and Central Luzon with 7,044.

        Sharp rises in dengue incidence were also recorded in the Zamboanga Peninsula from 687 last year to 2,250 (227 percent) this year; Bicol from 576 to 1,369 (137 percent); the Davao region from 1,724 to 4,078 (136 percent), and Western Visayas from 1,634 to 3,668 (124 percent).

        • http://www.philstar.com/headlines/2015/10/07/1508028/dengue-cases-nearing-100000-mark-doh (October 7, 2015.)

          ..The provinces of Bulacan and Cavite have declared a state of calamity in their respective areas due to the rising number of dengue patients and deaths brought about by the disease.

          Sen. Nancy Binay called for an inquiry into the increasing number of dengue cases in the country..

          • http://outbreaknewstoday.com/philippines-reports-more-than-200000-dengue-cases-in-2015/

            The “preliminary” final numbers are finally out and the Philippines saw an increase in dengue fever of nearly 65 percent in 2015 compared to the prior year. Through Dec. 31, the archipelago reported 200,415 suspected cases of dengue, including 598 deaths…

            ..In the past 50 years, the incidence of dengue worldwide has increased 30-fold, largely as a consequence of the growth of cities and increased travel…

          • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222740/

            “..The numbers of dengue disease cases being reported were highest in the most populated urban areas, such as NCR [25], [28], [29], [35]–[40]. However, the incidence of dengue disease per 100,000 population varied by year and by region. The dengue disease incidence rates per 100,000 population were highest in the NCR in 2000, CAR in 2001, Region VI in 2002, Region VII in 2007, Region XI in 2003, 2004, 2008 and 2009, and Region XII in 2005 and 2006 (Table S4) [25], [29]. Incidence rates for 2010 and 2011 were not available. However, in 2010, the highest number of cases by region was in Western Visayas (Region VI; 17,593 cases; 84 deaths; CFR 0.48%) [36]. In 2011, the highest number of cases by region was in NCR (15,427 cases; 93 deaths; CFR 0.60%), and the NCR area with the highest number of cases was Quezon City (4611 cases; 32 deaths; CFR 0.69%) [36]. The highest numbers of fatal dengue disease cases were in the NCR in 2001, 2003, 2004, 2005, and 2006 (121, 148, 131, 185, and 345 cases, respectively) [28]. By contrast, in 2002, the region with the highest number of fatal dengue disease cases was Central Visayas (Region VII; 107 cases) [28]…

            ..Few studies show any analysis of the seroepidemiology of dengue…In a prospective study of children admitted with fever without a clear focus to St Lukes Medical Centre in Quezon City, Metro Manila, from January 1999 to December 2001, 71.4% had dengue (confirmed by IgM and/or RT-PCR) and 1/3 had DHF [47], [48]. Furthermore, in another prospective fever surveillance study of patients with a mean age of 18 years admitted to San Lazaro Hospital, in Manila, Luzon, 87% of those with fever without a clear focus of infection had dengue, 7% of the cases were primary dengue infections (determined by IgM/IgG ELISA) [43].”

      • http://cnnphilippines.com/news/2017/12/09/Dengvaxia-DOH-Sanofi-Garin.html

        “What is obvious is there is collusion between the Philippine government headed then by the secretary of health Garin and the manufacturer of the vaccine Sanofi Pasteur,” Former Health Undersecretary Ted Herbosa said on the sidelines of a forum on Saturday.

        He belied Garin’s claim on Friday that he and Garin’s predecessor, former Health Secretary Enrique Ona, were aware of the government’s plan to administer Dengvaxia through a school-based dengue immunization program in 2016.

        “We never contemplated on using the dengue vaccine kasi experimental pa siya…Ibig sabihin nun hihintayin mo ‘yung final result of the study. Pagkatapos nun, mahaba po ang proseso ng drug development,” Herbosa said.

        [Translation: “We never contemplated on using the dengue vaccine because it’s experimental….This means you have to wait for the final result of the study. What follows is a long process of drug development.”]

        Over 40,000 volunteers participated in the Sanofi Pasteur dengue vaccine clinical study program in three phases in 15 countries in Asia, including the Philippines. A total of 29,000 volunteers received the vaccine. In 2014, Dengvaxia successfully completed phase III clinical studies to evaluate if the vaccine was effective.

      • https://www.reuters.com/article/sanofi-bribery/former-sanofi-employees-convicted-of-bribery-in-germany-idUSL6N0M01V620140303

        (March 3, 2014) A German court convicted two former employees of Sanofi-Aventis on bribery charges 10 months ago and imposed a fine on the French drugmaker last year, prosecutors said on Monday following a newspaper report.

        The court’s ruling also resulted in a 28 million euro fine for Sanofi. A spokeswoman for Sanofi-Aventis Deutschland GmbH confirmed the company had to pay that sum in connection with the case against the two former employees.

        “For Sanofi the matter is closed,” the spokeswoman said, referring to the Winsen court’s rulings. She added the company had cooperated with authorities during the investigation and had since further tightened its compliance system.

        • http://www.manilatimes.net/aquinos-p3-5b-purchase-dengue-vaccine-worst-case-corruption-ever/367353/ (WARNING – TIGLAO ARTICLE, use judgement in reading…)

          WAS there corruption on a massive scale, with former President Aquino 3rd earning hundreds of millions of pesos in dirty money from his administration’s purchase of Sanofi’s dengue vaccine Dengvaxia?

          If indeed it was a case of corruption, it would be among the biggest ever for a single corrupt deal, as just 10 percent of the P3-billion cost of the one million dosages of the vaccine purchased—without any bidding and through secret negotiations—is P350 million. It could have been likely more, considering that Sanofi’s $70 million sale to the Aquino administration gave it the much needed financial and advertising boost for a vaccine it had developed at a cost of $1.8 billion, yet which it could sell only $20 million worth in two years of aggressive marketing.

          • https://www.reuters.com/article/us-sanofi-dengue-philippines/philippines-to-seek-refund-of-59-million-from-sanofi-amid-vaccine-risk-idUSKBN1E2106

            MANILA (Reuters) – The Philippines will seek the return of 3 billion pesos ($59 million) it paid French drugmaker Sanofi for a dengue vaccine used to immunize hundreds of thousands of children that Sanofi has said could worsen the disease in some cases.

            “We will demand the refund of the 3 billion (pesos) paid for the Dengvaxia and (demand) that Sanofi set up an indemnification fund to cover the hospitalization and medical treatment of all children who might have severe dengue,” Health Secretary Francisco Duque told reporters on Friday.

            The Philippines last week suspended a national immunization program after Sanofi’s recent findings that there was a risk of severe dengue occurring in previously uninfected people who were inoculated with Dengvaxia. Manila also halted sale of the vaccine in the country and has ordered a probe into the matter.

            Duque said the number of children, ages 9 and above, inoculated with Dengvaxia has risen to about 830,000 from an initial estimate of nearly 734,000 after further verification by the Department of Health.

            The state program, which was launched in 2016, cost 3.5 billion pesos and Duque earlier said the government has already paid 3 billion pesos to Sanofi.

  • https://www.reuters.com/article/us-sanofi-dengue/trouble-mounts-for-sanofi-dengue-vaccine-over-safety-concerns-idUSKBN1DY26Y

    ..Brazil confirmed it already had recommended restricting use of the vaccine to those previously infected with dengue but had not suspended it entirely.

    Brazilian health regulator Anvisa, in an emailed statement to Reuters, said it had not received any reports of vaccine recipients dying or falling more severely ill because of the drug. It does not know how many people have received the vaccine in Brazil since its 2015 approval..

    ..“As far as we know, as far as we are made aware, there are no reported deaths that are related to dengue vaccination,” said Ruby Dizon, medical director at Sanofi Pasteur Philippines.

    A Philippine health official said the deaths of three children who received Dengvaxia, reported by a non-government organization, were not related to the vaccine.

    Nearly 734,000 children aged 9 and over in the Philippines have received one dose of the vaccine as part of a program that cost 3.5 billion pesos ($69.54 million)…

    • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355209/ 2013 May 28

      Current WHO guidelines recommend that safety assessment of dengue vaccines should include follow-up of dengue-vaccinated and control subjects for at least 3–5 years after completion of primary vaccination in Phase II and Phase III trials [4], [20]. Evidence from settings with different mosquito transmission intensities will be desirable as boosting from natural infection and different circulating serotypes and genotypes may impact on vaccine safety.

      • http://amp-vaccinology.org/sites/default/files/upload/files/CYD-TDV%20Pharmacovigilance_Module%205%20-%20v2(16Dec2016)_Eng.pdf

        Countries should have a dengue safety crisis management plan in place well in advance, including:
        o A frequent, proactive, and transparent review of dengue surveillance data.
        o Ongoing analysis and interpretation of passive data.
        o Giving the public a balanced overview of CYDTDV safety.
        o Preparing clear and efficient guiding principles and plans for communication with the media.
        o Minimizing misuse of data by the media

        • http://pps.org.ph/wp-content/uploads/2017/04/Serological-Testing.pdf

          There is currently no national data documenting dengue seroprevalence in the Philippines.
          However, in one study involving 1,066 Filipino children aged 2-16 years, dengue seropositivity rates as determined by plaque-reduction sero-neutralization assay were found to increase with increasing age: 58% in those age 2-4 years, 74.9% in those 5-8 years, 88.5% in those 9-12 years, and 93% in those 13-16 years.9

          Subsequently, a prospective longitudinal cohort study conducted in Cebu City among 1,008 children and adults starting from age 6 months and older showed that >98.3% of all those > 15 years developed evidence of multi-typic dengue HAI antibodies during the 12-month study period.

          However, only 17.5% of dengue infections that occurred were symptomatic; 82.5% developed subclinical infection.10

          In the absence of population-based serologic data, the WHO suggests the use of epidemiologic information (incidence, morbidity and mortality rate among infectious diseases) as an indicator.

          • http://www.pidsphil.org/download/RECOMMENDATION-DENGUE-VACCINE-MAY2016.pdf

            (PEDIATRIC INFECTIOUS DISEASE SOCIETY OF THE PHILIPPINES)

            A national dengue seroprevalence data is unavailable, except in two areas (Guadalupe, Cebu and San Pablo, Laguna), which showed 58% of children aged 2-4 years old, 75% of children aged 5-8 years, 89% of children aged 9-12 years old and 93% of children aged 13-14 years old, to be seropositive.1

            As part of a public health program, the Committee on Immunization suggests the following:

            1. Enhance the surveillance system that integrates epidemiological, entomological,
            environmental , clinical and laboratory data to include seroprevalence data.

            2. Disseminate information, education and communication materials on dengue vaccination
            for healthcare workers and the public.

            3. Provide enhanced training for healthcare workers on administering the vaccine, including cold chain management, the informed consent process as well as surveillance for Adverse Events Following Immunization (AEFIs).

            4. Emphasize the importance of coordinated strategies for dengue control, including vector control, adequate case management, and community programs to prevent transmission of dengue virus.

            5. Conduct a cost effectiveness study, utilizing local prevalence rates, facility utilization rates, and social costs, in order to justify and prioritize a long term dengue vaccination program.

  • http://www.gmanetwork.com/news/news/regions/635705/tarlac-student-suffers-from-severe-dengue-after-receiving-dengvaxia-shot/story/ – this thread is only for the severe dengue cases… (as always please take whatever is published with a grain of salt in this scrapbook approach)

    A student in Tarlac is suffering from severe dengue after she was immunized with the world’s first dengue vaccine, Dengvaxia.

    According to a report on Unang Balita on Thursday, while the student’s condition was improving, she is still confined in a hospital in Pampanga.

    The student had completed the three doses of Dengvaxia and had not been had dengue before.

    Meanwhile, another student was hospitalized due to dengue in Talisay City. She also received Dengvaxia shots and had no previous history of dengue.

    A Grade 5 student in Mariveles, Bataan was reported to have died of dengue in October last year.

    (does anyone know IF and WHERE this is centrally documented – IF EVER it is..)

  • additional comments from FB:

    1. why is the Philstar report about sicknesses starting from mid-March 2016 when vaccinations started in April 2016? (yes, that should be clarified – when did test phase 3 end?)

    2. 200K cases per year in the Philippines were mentioned (I would be happy to see sources)

    (plus of course local and international groups that approved of the vaccine)

    … the picture is getting bigger and rounder..

  • https://www.facebook.com/edselmaurice.salvana/posts/10204286812445997

    So I’m going to stick my head out because I feel there is a lot of confusion going around on the dengue vaccine again. This is my interpretation of the Sanofi release. For the record, I am an infectious diseases physician who deals with dengue on a daily basis. I am not a trained epidemiologist, but I do have some research expertise. I do not work for Sanofi and have never received any money from them. The reason I am speaking up is because I feel this vaccine has been demonized and that the ones who would benefit from it may not take it because of the uncertainty surrounding the interpretation of the recent statement.
    1. First of all, the vaccine was never meant to be given to seronegatives, based on the understanding that it would set up the antibody dependent enhancement (although there was no cytokine evidence of this in the severes). That is why it is only for use in high prevalence countries.
    2. There is a proliferation of igm and igg dengue test kits in the market which are meant for diagnosis of active dengue, not necessarily past dengue infection where the titers are much lower. The best test will be an elisa done in a proper hospital or research lab. The vast majority of lateral flow rapid assays done by diagnostic labs are not designed to detect past infection in someone who does not have active dengue. Therefore, there is no readily accessible reliable way for a physician to diagnose past infection in someone who does not have dengue. If the test is positive then it is useful, but if it is negative it is not certain.
    3. The statement reiterated the efficacy of the vaccine up to 6 years, and this is a good thing. If you have started the series, you probably should complete it otherwise you wont get the full benefit. We need to emphasize this because people may not complete their vaccination because of the uncertainty.
    4. We are talking of a safety SIGNAL, not a statistically significant harm. This is why they used the word “could harm” versus definitely harms. No one has died from this. But lots of people have died from dengue. You decide which is a bigger problem and if your risk of getting dengue is higher you should take the vaccine within the recommended parameters. Put another way, we are talking about definite benefit versus possible harm.
    5. I agree this should not have been used immediately for mass vaccination until after SAGE released its recommendations. Whatever DOH’s reason for going ahead with it, they will have to explain. However this should not discredit the scientific evidence that the vaccine works when used correctly. Based on the seroprevalence studies in the Philippines, the seroprevalence of at least one dengue infection is above 90% in those ages 12 and above. And if you have had at least one episode of dengue (like me), you should absolutely not hesitate to get the vaccine. The vaccine decreases the risk of severe dengue in this group of people by about 90% for sure. Statistically significant.
    Bottom line, this is a GOOD vaccine when used correctly. Talk to your doctor if it is appropriate for you. Only you can make decisions about your health, but you need to make an informed decision.

    • https://www.facebook.com/jozy.acosta/posts/10155368490493585

      With all the misinformation and politicking about the dengue vaccination program, it’s time to set the record straight.
      1. DOH’s dengue vaccination program was not administered prior to the drug Dengvaxia’s approval for sale.
      Dengvaxia had passed three of four phases of clinical trials. Passing Phase 3, typically the most expensive, time-consuming and difficult phase, means the drug company can already apply for approval to market the product, which Sanofi did and which it obtained.
      Phase 4, called post-marketing suveillance, is in-market monitoring conducted AFTER the drug has already been approved for consumer sale, to determine such things as long-term effects, contraindications in unstudied segments, new uses, dosage adjustments, etc. This is where the Philippines came in and it was not alone – a total of 11 countries approved it for use (source: Rappler), with Mexico licensing it in December 2015 (source: WHO).
      WHO had recommended it for use in areas where data “indicate a high burden of disease”.
      While the regional WHO office responsible for the Philippines clarified that it never recommended use of the drug in national immunization programs, it did “outline a series of considerations national governments should take into account in deciding whether to introduce the vaccine” and notes that the Philippines met those conditions in the three regions where it was initially rolled out. (Source: WHO Western Pacific Region Dec. 5 2017 statement.)
      It’s worth noting that one of those parameters – high proportion of at least 70% of the community already previously exposed to the disease – significantly reduces the risk factor of the vaccine.
      2 Is PNoy to blame?
      Much has been said about who is to blame for the dengue vaccine uproar – the PNoy admin for approving ithe program or the Duterte admin for continuing it despite initially deciding against it, resulting in over half of the 700k+ vaccinations happening during Duterte’s term.
      I would hazard a guess that PNoy’s people did a risk-benefit assessment and made a judgement call, given the gravity of the disease here and the WHO endorsement. The Duterte administration had an opportunity to discontinue the implementation. It’s possible that the current officials didn’t do so because they arrived at the same conclusion that PNoy’s people did.
      The entire finger-pointing is unproductive. Simply put, officials of both admins made the same decision based on information available to them at the time.
      Perhaps the better questions are: How many are at risk and is the risk worth it vis-a-vis the number who were protected? Can we manage that risk? Can Sanofi be enlisted in helping manage that risk?
      3. The drug is not lethal. It does not merit the shrill accusations of genocide nor the facial contortions of not-newsworthy bloggers.
      Dengvaxia increases the severity of expressions of dengue among those who were not previously exposed to dengue and contracts it after being vaccinated. Nothing I read says that it increases susceptibility to the disease nor mortality from it if treated as indicated.
      In fact, in its updated FAQs, WHO maintains that “the vaccine significantly protects against hospitalized and severe dengue” in individuals previously exposed to dengue, and still recommends its use among those who have been previously exposed, emphasizing that this narrowed application is a precautionary and interim measure pending a full review. (Nevertheless, on a country level, WHO supported the precautionary suspension of the vaccination program in the Philippines.)
      Time, money and energy are better spent on managing the risk among those affected. Unfortunately, data does not exist on who these might be, precluding any preemptive action. The most we can do is do what we’ve always done – treat dengue patients the best we can (this time, hopefully with the assistance of Sanofi given their role in this mess).
      The bright spot is that the risk uncovered by the new information can actually be effectively controlled by simple blood-testing and taking of medical histories.
      4. It does not cost P9 a pop.
      Here is where we venture into fake news troll territory.
      Sonza, fact check naman. But you know what’s needed before fact-checking? Logic. It’s that nagging feeling that signals to you that something is not quite correct, and gives you that compulsion to dig deeper.
      Think about it. You’re a drug company in the business of making mega-bucks. You have a patent for a formulation that is the first and so far the only vaccine against a disease that affects millions of people worlwide. Wouldn’t you try to make truckloads of money off of it while you still have a monopoly of the market, to pay for the millions you spent on decades of research and development, not to mention the millions more you’ll spend sending doctors to expensive junkets?
      A troll sent me a meme showing a site where Dengvaxia is purportedly sold at the equivalent of nine pesos a dose, whereas the PNoy admin bought it at P1000. Oh wow, millions pocketed by PNoy!
      But wait. Sanofi, the patent owner, is not listed as the seller. Could Astellas Pharma India, the alleged seller, be an authorized reseller?
      A cursory search for the company unearths a warning from them on unscrupulous persons unlawfully using their name to sell drugs online (it does not mention trolls using it to generate fake news, alas). It states that the only drugs they sell are listed in their site. The list does not included Dengvaxia.
      Sigh. Sabi nga nila, walang maloloko kung walang tanga. Ay, ako pala nagsabi nun.
      Ang mas malala, yung pinamukha na sayo ang katotohanan pero todo depensa ka pa rin sa fake news mo. Walang vaccine sa katangahan. Double sigh.

      • https://www.facebook.com/sylvia.claudio.5/posts/10155125784722014?pnref=story

        Dengue Vaccine
        Here is what the initial accusations were: that the dengue vaccine has been used by the administration of Garin/Pnoy (or the Ubial/Duts, depending on political camp) to place people in danger mainly because the vaccine is unsafe. In truth the vaccination program was started under the Pnoy administration and continued under PDuts. Sorry na lang yung mga tao na may political agenda na “everything Pnoy is horrible and PDuts is the anti-Pnoy.”
        It seems clear to me that they were in compliance with the WHO recommendations at that time, same compliance now in stopping the vaccines for review.
        I do not know what your politics are around the WHO but medical treatments are always contested and I follow the WHO. Call me conservative that way.
        Some people now ask, “show us the data that you were actually following WHO recommendations that it be used in endemic populations.” I suggest you talk to the DOH epidemiology unit who are also competent professionals. As it is, whole populations are panicking because you make accusations about “show us the data”.
        The other accusation is that the drugs are overpriced. That one is yet to be proven. What I know is that people like Gwen Garcia held the DOH budget hostage if they did not implement the vaccine. (See the Pinoy Ako Blog for “resibo”.)
        People accuse me of politicising all the time. As a rebellious sort whose rebelliousness got super validated by being an academic from UP, I am indeed always critical and this has been true whoever sits in Malacañang.
        But part of being critical is holding your “banat” until you get the facts.
        Find out please if Sanofi lobbied and unduly influenced people like Garcia who from all indications has flip-flops on the issue. Regardless of the science of the vaccine, this would not be right.
        Find out if the government paid more for the vaccines. In this regard my sources in DOH are talking with 2 mouths which is always part of the DOH game. But I trust so far those who say this did not happen. I am open to a contrary finding because one journalist I trust says otherwise.
        In the meantime, I suggest we inform ourselves better before we panic people with our certainties which turn out to be maybes.

        • https://www.facebook.com/sylvia.claudio.5/posts/10155128069787014?pnref=story

          More on the dengue vaccine by Junice Junice L. Demeterio Melgar
          Let us do the math on the risks of the Dengue vaccine.
          The seropositivity level, which is an indication of a population’s exposure to dengue, was in the range of 89-98%, based on tests made in San Pablo City. This value was extrapolated to apply to the endemic areas in NCR, Region 3 and a few other places where the vaccine was introduced. WHO requires a minimum level of 70% seropositivity as basis for doing vaccination. The vaccine would be risky to the seronegative population, i.e. those who were not exposed to dengue.
          Applying the WHO’s maximum at-risk value of 30% to the 700,000 population of children vaccinated, there would be 210,000 at elevated risk of severe Dengue. The additional actual severe Dengue, according to Sanofi’s latest estimate,would be 2 per thousand. 210,000 X 2/1000 is 420. So 420 is the number of cases that the health system is expected to handle at severity levels 1 and 2, out of a 4 point scale. Sanofi has said there have been no deaths and no severity level 4.
          Obviously, we need to monitor the 210,000 at risk and take care of the additional 420 who are estimated to present with severe dengue.
          But let us also remember that 70% of the 700,00 population, or 490,000, will benefit from the protection of the vaccine.

          • https://www.facebook.com/sylvia.claudio.5/posts/10155128120632014

            More again from Junice L. Demeterio Melgar:
            There is currently a lot of anxiety regarding the possible “severe effects” of the dengue vaccine in kids given the vaccine in dengue-endemic areas. I was with the Family Health Office of the Dept. of Health in 2016 when the program was started and supported the initiative despite the criticism of some sectors that the vaccine had not been tested enough for safety and that it was too expensive. My own reasoning then -and until now – is that the benefit to public health is greater than the cost. Since then, I know that the Family Health Office and the Epidemiology Bureau of the DOH have been doing due diligence in monitoring all adverse effects from the beginning. As far as I know there have been no “severe” complications nor deaths directly attributable to the vaccine. The Secretary of Health has recently stopped the vaccinations and ordered a thorough review of the impact. Let us support that. But I appeal to fellow health workers to help stop the panic and the anti-vaccine paranoia that will put more people into greater harm.
            Below is the statement from the Brazilian Minister of Health who has deemed it safe and wise to continue with the Dengue vaccination in the localities where endemic dengue was harming and killing citizens prior to the vaccine.
            ———————————————————————————
            Press release of the government of Brazil released Nov 30
            NOTE – DENGUE ANVISA VACCINE
            The Secretary of State for Health will maintain the offer of the vaccine against dengue in the 30 municipalities defined to receive the campaign since 2016. The Anvisa Note, released on Wednesday, 11/29/17, does not interfere with the strategy adopted in Paraná following criteria:
             Anvisa’s statement was motivated by the official notification of the production company, which continues to monitor vaccination results not only in Brazil, but also in other countries that are using the product.
             The decision of the Government of Paraná to adopt the vaccine was based on consistent epidemiological data, following recommendations of the World Health Organization, academic societies and the release of ANVISA. Thus, the campaign was directed only at 30 endemic and epidemic municipalities. 82% of the cases registered in Paraná, 91% of the serious cases and 87% of the dengue deaths in the State, which faced consecutive epidemics, recorded a large number of cases.
             Since 80% of the cases of first dengue infection are asymptomatic, that is, the person does not identify the disease, even those who did not have the diagnosis and live in endemic cities may have had contact with the virus, which reinforces the decision of Paraná to vaccinate in the selected municipalities.
             Scientific evidence clearly demonstrates that the vaccine does not cause dengue and all identified cases of adverse events have been fully recovered with routine treatment.
             Paraná vaccinated 300,000 people against dengue fever in three stages of the campaign: August / September 2016, March / April 2017 and September / October 2017. The State Department of Health monitors those vaccinated in the 30 municipalities that received the campaign and did not report any serious adverse reactions. Only minor local reactions were reported.
             In addition to surveillance for adverse reactions, in which no serious reaction has been reported, the Government is conducting cross-monitoring between vaccinates and new confirmed cases of dengue. Since August 2016, when the vaccination campaign against dengue was defined, 1061 cases of dengue fever in Paraná and no deaths from the disease were confirmed, and only 40 people vaccinated were notified with mild dengue fever without laboratory confirmation, only clinical suspicion. This represents 0.01% of the total vaccinated. In the previous epidemiological period, between August 2015 and July 2016, Paraná registered 56,351 cases and 63 deaths from dengue.
             Effectiveness and safety studies of the vaccine are being carried out in the 30 municipalities that received the campaign. In addition to technicians from the State Department of Health, they participate in the professional studies of the Federal University of Paraná (UFPR), the Pequeno Príncipe Hospital in Curitiba, representatives of the Ministry of Health, Pan American Health Organization (PAHO), Sabin Institute and Santa Casa de São Paulo and University of São Paulo (USP).

  • http://opinion.inquirer.net/109289/whats-stake-dengue-vaccine#ixzz50Wl7SAUr – Gideon Lasco

    The debate over the dengue vaccine is nothing new in the medical community, but it is far more complex than how it is being presented in popular discourse. In the first place, there is actually broad consensus—based on existing data — that the vaccine has benefits among those who’ve had previous dengue and risks among those who haven’t. Doctors also know that every intervention has risks and benefits, and it’s a matter of weighing them — a very difficult task, especially when dealing with large populations, ever-changing medical knowledge, and a particularly complex virology.

    The disagreements lie in whether risks were fully considered at the time the decision was made (critics, citing the haste and lack of prior World Health Organization endorsement, claim they weren’t), whether the economic cost of P3 billion and medical risks justified a mass vaccination program (Sanofi, citing its own research, says the cost of vaccinations is less than the hospitalizations they would prevent), whether vested political and pharmaceutical interests were involved, and whether, in light of new evidence, the program should be continued. Fortunately, the Department of Health seems to be taking a prudent course by suspending the vaccination program and calling on experts to adjudicate the matter…

  • karlgarcia

    In the Philippines it is hard to say who had a previous nfection.

    http://www.philstar.com/headlines/2017/12/05/1765469/dengvaxia-still-beneficial-sanofi

    “…
    important to note, however, is that it depends on which country you might be in. It’s sometimes not easy to really identify who had a previous infection because we saw three out of four cases can have no symptoms,” she said.”

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