Dengue in Puerto Rico

update: CDC report of last year's dengue outbreak in PuertoRico. 

During 2024, Puerto Rico reported 6,291 dengue cases and surpassed the epidemic threshold, prompting declaration of a local public health emergency. Approximately one half of patients (52.3%) were hospitalized, 264 (4.2%) had severe dengue cases, and 11 (0.2%) persons died. Persons aged 10–19 years accounted for 28.4% of severe cases. Since most cases have few symptoms or might not be sick enough to see a physician.

the rest is about treatment (supportive,, including fluids) and mosquito control, things that have been used for a century.

So is there any treatment for Dengue? No medicines?

2018 article suggests ivermectin might help but it was a poor study and the errors of the paper corrected here. 

(note a recent article reported hundreds of papers were recently removed from publication because of flaws)

this study showed some lab improvements but wasn't conclusive.

https://academic.oup.com/cid/article/72/10/e594/5943555?login=false

problem? Anti virals have to be given early to work, and the vague symptoms might not be enough to see a physician that early.

https://pmc.ncbi.nlm.nih.gov/articles/PMC8544673/

about possible anti viral medicine: problem: Hard to prove they work

here kitty kitty kitty

 From the CDC: some cats caught bird flu. 

Well, that happens. Outdoor cats catch and eat birds, some of whom are infected.

 But these were indoor cats. However someone in their household worked with milk transport or in dairy farms. They refused testing but the family members tested were negative.

Highly Pathogenic Avian Influenza A(H5N1) Virus Infection of Indoor Domestic Cats Within Dairy Industry Worker Households — Michigan, May 2024 published February 20, 2025 / 74(5);61–65 Summary What is already known about this topic? Outdoor cats on U.S. dairy farms have been infected with highly pathogenic avian influenza (HPAI) A(H5N1) virus; infection has not been reported in indoor cats.HPAI A(H5N1) virus was detected in two indoor domestic cats with respiratory and neurologic illness that lived in homes of dairy workers but had no known direct exposure to HPAI A(H5N1)–affected farms. Both dairy workers declined testing; other household members received negative test results for influenza A.

Grok on Dengue vaccine

 so I got a pop up about the new Grok 3 and it said ask them anything. And so I asked about these new vaccines (see below):

does the attenuated Dengue vaccine induce immunological problems Completed DeepSearch 35s Tap to read 78 sources 1. Dengue Fever and the New Dengue Vaccine The dengue vaccine is 80.2% effective in preventing dengue fever from all serotypes and reduces hospitalization by 90.4%. It can be administered to individuals aged 4 to 60 years without the need for a prior immune system test. · The vaccine is safe, and any side effects encountered are generally mild, such as pain at the injection site, headaches and muscle pain, with these side effects usually subsiding within 1-3 days. The dengue virus has 4 serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. Typically, dengue fever presents with mild symptoms or may even be asymptomatic. However, in some cases it can lead to severe symptoms, progressing to shock and even death. It is a disease that is difficult to predict whether an individual will experience mild or severe symptoms. The 4 serotypes of the dengue virus circulate and alternate in causing outbreaks, which leads to varying serotypes spreading each year. samitivejhospitals.com Show thinking Researching vaccine basics An attenuated vaccine uses a weakened virus to trigger immunity. I'm curious how this applies to the Dengue vaccine. Searching for "approved dengue vaccines" Dengvaxia and TAK-003 are live attenuated dengue vaccines, fitting the description. I'm exploring if they cause immunological issues. Antibody-dependent enhancement (ADE) is a concern with Dengvaxia, especially for those not previously infected. This could worsen subsequent dengue infections, so that's worth noting. ADE is more about how the vaccine interacts with future infections, not directly causing problems. I'm wondering if there are other immunological issues to consider. Browsing www.fda.gov for "side effects" That last search didn't help much. I'm thinking of looking for the package insert to find detailed side effects. Searching for "Dengvaxia side effects" Dengvaxia | European Medicines Agency (EMA) www.ema.europa.eu Dengvaxia: Basics, Side Effects & Reviews www.goodrx.com Dengue vaccine - Wikipedia en.wikipedia.org Dengvaxia Side Effects: Common, Severe, Long Term www.drugs.com Dengvaxia Uses, Side Effects & Warnings www.drugs.com Common side effects of Dengvaxia include headache, pain at the injection site, and muscle pain Dengvaxia EMA. There's a risk of severe dengue in those not previously infected, due to ADE, which can worsen future infections Dengvaxia CDC. The vaccine itself doesn't inherently cause immunological problems, but ADE can occur in certain groups. I'm considering if this counts as an induced issue. For those previously infected, Dengvaxia seems beneficial, not problematic. Let's see how this fits the question's focus. The vaccine induces antibodies that can enhance virus infection in future cases, leading to severe disease. I'm thinking this counts as an immunological problem. The question's wording is ambiguous, but "induce" suggests causing issues, including ADE in specific scenarios. Let's explore if there are direct immune disorders too. Searching for "autoimmune side effects of dengue vaccine" Autoimmunity in dengue pathogenesis - PubMed pubmed.ncbi.nlm.nih.gov Autoimmunity in dengue pathogenesis - ScienceDirect www.sciencedirect.com About a Dengue Vaccine | Dengue | CDC www.cdc.gov Dengue tetravalent vaccine, live (subcutaneous route) - Mayo Clinic www.mayoclinic.org Dengue Fever and the New Dengue Vaccine www.samitivejhospitals.com Studies suggest dengue infection can lead to autoimmune responses, but I'm not finding direct links to the vaccine causing these. Investigating autoimmune links Complete 78 web pages Key Points Yes, the attenuated dengue vaccine can cause immunological problems, especially antibody-dependent enhancement (ADE) in some people. ADE can make dengue more severe if the person gets infected after vaccination and wasn't previously exposed to dengue. This risk is mainly with vaccines like Dengvaxia, but may vary by vaccine type. Overview The attenuated dengue vaccine, such as Dengvaxia, is designed to protect against dengue by using a weakened form of the virus. However, it can lead to immunological issues, particularly in people who haven't had dengue before. This is due to a process called antibody-dependent enhancement (ADE), where the vaccine might make a future dengue infection worse instead of better. This is surprising because vaccines are typically expected to only protect, not potentially harm in certain cases. It's important to know your dengue exposure history before getting vaccinated, as it affects the safety and effectiveness. Details for Consideration Who Is Affected? The risk of ADE is higher in individuals who were not previously infected with dengue and receive the vaccine, then later get infected. For those already exposed to dengue, the vaccine is generally safe and effective. What Is ADE? ADE happens when antibodies from the vaccine help the virus enter cells more easily, potentially leading to more severe disease if the person gets dengue later. This is a known concern with live attenuated dengue vaccines. Other Vaccines: Another attenuated vaccine, TAK-003, shows promise with fewer ADE issues, but more research is needed to confirm this. The specific vaccine matters for safety. Comprehensive Analysis of Attenuated Dengue Vaccine and Immunological Impacts This section provides a detailed examination of the attenuated dengue vaccine, focusing on its potential to induce immunological problems, with a particular emphasis on antibody-dependent enhancement (ADE) and other related concerns. The analysis is grounded in extensive web-based research, including clinical trial data, regulatory approvals, and scientific literature, to ensure a thorough understanding for healthcare professionals, researchers, and informed laypersons. Background on Attenuated Dengue Vaccines Attenuated dengue vaccines use live, weakened forms of the dengue virus to stimulate an immune response without causing the full disease. Notable examples include Dengvaxia (CYD-TDV) by Sanofi Pasteur and TAK-003 by Takeda. Dengvaxia, a live recombinant tetravalent vaccine, was the first licensed dengue vaccine, approved in various countries since 2015, while TAK-003, also live-attenuated, received approval in the European Union in 2022 and other regions like Indonesia (Takeda's QDENGA Approval). These vaccines aim to protect against all four dengue virus serotypes (DENV-1, DENV-2, DENV-3, DENV-4), which is crucial given the global burden of dengue, affecting an estimated 390 million people annually (Dengue Vaccines Update). Immunological Problems: Focus on Antibody-Dependent Enhancement (ADE) One significant immunological problem associated with attenuated dengue vaccines is ADE, a phenomenon where non-neutralizing or sub-neutralizing antibodies facilitate viral entry into cells via Fcγ receptors, potentially increasing viral replication and disease severity. This is particularly noted with Dengvaxia. Research indicates that Dengvaxia can sensitize dengue-naïve recipients to severe dengue upon subsequent natural infection, leading to restricted FDA approval in 2019 for use only in individuals with prior laboratory-confirmed dengue infection (FDA Dengvaxia Approval). This restriction arose from concerns that vaccination without prior exposure could worsen outcomes, as seen in the Philippines in 2017, where over 733,000 children were vaccinated regardless of serostatus, leading to controversy due to increased severe dengue cases (Dengue Vaccine Wikipedia). ADE is linked to the vaccine eliciting cross-reactive antibodies against the pre-membrane (prM) and fusion loop epitope (FLE) of DENV, which are not fully neutralizing and can enhance infection in later exposures (Antibody-Dependent Enhancement Challenge). This risk is higher in baseline seronegative individuals, with studies showing increased hospitalization rates for dengue type 3 among vaccinated seronegative participants in some trials (New Dengue Vaccine Efficacy). Comparative Analysis: Dengvaxia vs. TAK-003 While Dengvaxia has clear ADE concerns, TAK-003 appears to have a different safety profile. Clinical trials, such as the phase 3 efficacy study (NCT02747927), suggest TAK-003 is efficacious against symptomatic dengue over three years, with no significant ADE issues reported in the literature reviewed (Three-Year Efficacy TAK-003). However, the general concern about ADE with live attenuated vaccines remains, and long-term data are still being evaluated. TAK-003's approval in Indonesia without pre-vaccination testing suggests a broader application, but U.S. approval was withdrawn in 2023 due to data collection disagreements with the FDA, indicating ongoing scrutiny (Takeda Withdrawal BLA). Other Potential Immunological Issues Beyond ADE, the survey of side effects for Dengvaxia includes common reactions like headache, injection site pain, and fever, with rare severe allergic reactions reported (Dengvaxia Side Effects). There is no strong evidence from the searches linking attenuated dengue vaccines directly to autoimmune disorders, despite dengue infection itself being associated with autoimmune features in case reports (Autoimmune Features Dengue). General vaccine safety literature suggests that while vaccines can theoretically trigger autoimmune diseases, epidemiological studies do not support this for systemic autoimmune diseases, and no specific cases were found for dengue vaccines (Vaccinations and Autoimmune Diseases). Clinical Implications and Recommendations The immunological problems, particularly ADE, necessitate careful screening for prior dengue exposure before vaccination with vaccines like Dengvaxia. The CDC recommends Dengvaxia for children aged 9–16 years with laboratory-confirmed previous dengue infection living in endemic areas, highlighting the importance of serostatus (CDC Dengue Vaccine). For TAK-003, while initial data suggest fewer ADE concerns, ongoing surveillance is crucial, especially given its recent approvals and the need for long-term efficacy and safety data. Summary Table of Vaccine Characteristics and ADE Risk Vaccine Type Approval Status ADE Risk in Seronegative Common Side Effects Dengvaxia Live Recombinant Tetravalent Approved in US, EU, etc. High Headache, injection site pain, fever TAK-003 Live-Attenuated Tetravalent Approved in EU, Indonesia Low (Preliminary Data) Viral upper respiratory infection, etc. This table summarizes key attributes, aiding in understanding the differential immunological risks. Conclusion In conclusion, attenuated dengue vaccines, particularly Dengvaxia, can induce immunological problems, with ADE being the most significant, especially in dengue-naïve individuals. This risk underscores the importance of pre-vaccination screening. TAK-003 shows promise with potentially lower ADE risks, but further research is needed. Healthcare providers should consider individual serostatus and vaccine type to mitigate these immunological challenges. Key Citations Dengvaxia European Medicines Agency Takeda's QDENGA Approval Dengue Vaccines Update FDA Dengvaxia Approval Dengue Vaccine Wikipedia New Dengue Vaccine Efficacy Three-Year Efficacy TAK-003 Takeda Withdrawal BLA Antibody-Dependent Enhancement Challenge Dengvaxia Side Effects Autoimmune Features Dengue Vaccinations and Autoimmune Diseases CDC Dengue Vaccine https://pubmed.ncbi.nlm.nih.gov/23332423/ Dengue is one of the most important vector-borne viral diseases. With climate change and the convenience of travel, dengue is spreading beyond its usual tropical and subtropical boundaries. Infection with dengue virus (DENV) causes diseases ranging widely in severity, from self-limited dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome. Vascular leakage, thrombocytopenia, and hemorrhage are the major clinical manifestations associated with severe DENV infection, yet the mechanisms remain unclear. Besides the direct effects of the virus, immunopathogenesis is also involved in the development of dengue disease. Antibody-dependent enhancement increases the efficiency of virus infection and may suppress type I interferon-mediated antiviral responses. Aberrant activation of T cells and overproduction of soluble factors cause an increase in vascular permeability. DENV-induced autoantibodies against endothelial cells, platelets, and coagulatory molecules lead to their abnormal activation or dysfunction. Molecular mimicry between DENV proteins and host proteins may explain the cross-reactivity of DENV-induced autoantibodies. Although no licensed dengue vaccine is yet available, several vaccine candidates are under development. For the development of a safe and effective dengue vaccine, the immunopathogenic complications of dengue disease need to be considered. Key Points Yes, the attenuated dengue vaccine can cause immunological problems, especially antibody-dependent enhancement (ADE) in some people. ADE can make dengue more severe if the person gets infected after vaccination and wasn't previously exposed to dengue. This risk is mainly with vaccines like Dengvaxia, but may vary by vaccine type. Overview The attenuated dengue vaccine, such as Dengvaxia, is designed to protect against dengue by using a weakened form of the virus. However, it can lead to immunological issues, particularly in people who haven't had dengue before. This is due to a process called antibody-dependent enhancement (ADE), where the vaccine might make a future dengue infection worse instead of better. This is surprising because vaccines are typically expected to only protect, not potentially harm in certain cases. It's important to know your dengue exposure history before getting vaccinated, as it affects the safety and effectiveness. Details for Consideration Who Is Affected? The risk of ADE is higher in individuals who were not previously infected with dengue and receive the vaccine, then later get infected. For those already exposed to dengue, the vaccine is generally safe and effective. What Is ADE? ADE happens when antibodies from the vaccine help the virus enter cells more easily, potentially leading to more severe disease if the person gets dengue later. This is a known concern with live attenuated dengue vaccines. Other Vaccines: Another attenuated vaccine, TAK-003, shows promise with fewer ADE issues, but more research is needed to confirm this. The specific vaccine matters for safety. Comprehensive Analysis of Attenuated Dengue Vaccine and Immunological Impacts This section provides a detailed examination of the attenuated dengue vaccine, focusing on its potential to induce immunological problems, with a particular emphasis on antibody-dependent enhancement (ADE) and other related concerns. The analysis is grounded in extensive web-based research, including clinical trial data, regulatory approvals, and scientific literature, to ensure a thorough understanding for healthcare professionals, researchers, and informed laypersons. Background on Attenuated Dengue Vaccines Attenuated dengue vaccines use live, weakened forms of the dengue virus to stimulate an immune response without causing the full disease. Notable examples include Dengvaxia (CYD-TDV) by Sanofi Pasteur and TAK-003 by Takeda. Dengvaxia, a live recombinant tetravalent vaccine, was the first licensed dengue vaccine, approved in various countries since 2015, while TAK-003, also live-attenuated, received approval in the European Union in 2022 and other regions like Indonesia (Takeda's QDENGA Approval). These vaccines aim to protect against all four dengue virus serotypes (DENV-1, DENV-2, DENV-3, DENV-4), which is crucial given the global burden of dengue, affecting an estimated 390 million people annually (Dengue Vaccines Update). Immunological Problems: Focus on Antibody-Dependent Enhancement (ADE) One significant immunological problem associated with attenuated dengue vaccines is ADE, a phenomenon where non-neutralizing or sub-neutralizing antibodies facilitate viral entry into cells via Fcγ receptors, potentially increasing viral replication and disease severity. This is particularly noted with Dengvaxia. Research indicates that Dengvaxia can sensitize dengue-naïve recipients to severe dengue upon subsequent natural infection, leading to restricted FDA approval in 2019 for use only in individuals with prior laboratory-confirmed dengue infection (FDA Dengvaxia Approval). This restriction arose from concerns that vaccination without prior exposure could worsen outcomes, as seen in the Philippines in 2017, where over 733,000 children were vaccinated regardless of serostatus, leading to controversy due to increased severe dengue cases (Dengue Vaccine Wikipedia). ADE is linked to the vaccine eliciting cross-reactive antibodies against the pre-membrane (prM) and fusion loop epitope (FLE) of DENV, which are not fully neutralizing and can enhance infection in later exposures (Antibody-Dependent Enhancement Challenge). This risk is higher in baseline seronegative individuals, with studies showing increased hospitalization rates for dengue type 3 among vaccinated seronegative participants in some trials (New Dengue Vaccine Efficacy). Comparative Analysis: Dengvaxia vs. TAK-003 While Dengvaxia has clear ADE concerns, TAK-003 appears to have a different safety profile. Clinical trials, such as the phase 3 efficacy study (NCT02747927), suggest TAK-003 is efficacious against symptomatic dengue over three years, with no significant ADE issues reported in the literature reviewed (Three-Year Efficacy TAK-003). However, the general concern about ADE with live attenuated vaccines remains, and long-term data are still being evaluated. TAK-003's approval in Indonesia without pre-vaccination testing suggests a broader application, but U.S. approval was withdrawn in 2023 due to data collection disagreements with the FDA, indicating ongoing scrutiny (Takeda Withdrawal BLA). Other Potential Immunological Issues Beyond ADE, the survey of side effects for Dengvaxia includes common reactions like headache, injection site pain, and fever, with rare severe allergic reactions reported (Dengvaxia Side Effects). There is no strong evidence from the searches linking attenuated dengue vaccines directly to autoimmune disorders, despite dengue infection itself being associated with autoimmune features in case reports (Autoimmune Features Dengue). General vaccine safety literature suggests that while vaccines can theoretically trigger autoimmune diseases, epidemiological studies do not support this for systemic autoimmune diseases, and no specific cases were found for dengue vaccines (Vaccinations and Autoimmune Diseases). Clinical Implications and Recommendations The immunological problems, particularly ADE, necessitate careful screening for prior dengue exposure before vaccination with vaccines like Dengvaxia. The CDC recommends Dengvaxia for children aged 9–16 years with laboratory-confirmed previous dengue infection living in endemic areas, highlighting the importance of serostatus (CDC Dengue Vaccine). For TAK-003, while initial data suggest fewer ADE concerns, ongoing surveillance is crucial, especially given its recent approvals and the need for long-term efficacy and safety data. Summary Table of Vaccine Characteristics and ADE Risk Vaccine Type Approval Status ADE Risk in Seronegative Common Side Effects Dengvaxia Live Recombinant Tetravalent Approved in US, EU, etc. High Headache, injection site pain, fever TAK-003 Live-Attenuated Tetravalent Approved in EU, Indonesia Low (Preliminary Data) Viral upper respiratory infection, etc. This table summarizes key attributes, aiding in understanding the differential immunological risks. Conclusion In conclusion, attenuated dengue vaccines, particularly Dengvaxia, can induce immunological problems, with ADE being the most significant, especially in dengue-naïve individuals. This risk underscores the importance of pre-vaccination screening. TAK-003 shows promise with potentially lower ADE risks, but further research is needed. Healthcare providers should consider individual serostatus and vaccine type to mitigate these immunological challenges. Key Citations Dengvaxia European Medicines Agency Takeda's QDENGA Approval Dengue Vaccines Update FDA Dengvaxia Approval Dengue Vaccine Wikipedia New Dengue Vaccine Efficacy Three-Year Efficacy TAK-003 Takeda Withdrawal BLA Antibody-Dependent Enhancement Challenge Dengvaxia Side Effects Autoimmune Features Dengue Vaccinations and Autoimmune Diseases CDC Dengue Vaccine

aspirin!

 

dengue vaccine: New and approved? Maybe.

PhilInquirer notes that the local physicians groups is pushing the government to approve of a European dengue vaccine.

The Philippine Medical Association (PMA) has urged President Marcos to intervene and expedite the approval of new-generation dengue vaccines amid the surge of dengue cases in the country.

The appeal was made by the country’s doctors at the launching of the Empowering Networks to Defeat Dengue or End Dengue Coalition—founded by PMA, in partnership with health-care organizations, the academe, researchers and advocates—on Tuesday in Quezon City, with the collective goal of achieving zero dengue deaths by 2030.

In a letter addressed to Mr. Marcos read during the event by Dr. Erica Tania Davillo, chair of the PMA’s ad hoc committee on dengue advocacy, the organization acknowledged that the safety of dengue vaccines was of “utmost concern” because of the country’s previous experience with Dengvaxia.

The PMA specifically cited Qdenga of Japanese pharmaceutical company Takeda, which is approved in 40 countries and one of the only two dengue vaccines approved by the World Health Organization (WHO) to prevent dengue in highly endemic countries like the Philippines. (The other WHO-approved dengue vaccine is Dengvaxia of French pharmaceutical giant Sanofi Pasteur.)

The WHO in May last year cleared Qdenga for use in children aged 6 to 16 in areas with high infection rates. The prequalification made it eligible for procurement through United Nations agencies like the UN Children’s Fund. The vaccine, which contains weakened versions of the four dengue virus strains, is recommended as a two-dose schedule with a minimum interval of three months between doses.

Dengue disease is caused by infection with dengue virus, which is transmitted to humans through the bite of mosquitos. This vaccine contains attenuated versions of the 4 virus serotypes. These versions cannot cause the disease, but they ‘teach’ the immune system (the body’s natural defences) to defend the body against the virus. When a person is given the vaccine, the immune system identifies the attenuated serotypes as foreign and makes antibodies against them. When a person is later exposed to the virus, the immune system recognises it and can quickly make many more antibodies, which then neutralise the virus before it can cause dengue disease.

so it's not an mRNA vaccine but an old fashioned attenuated virus type.

But the complications of dengue happen in folks who have had the disease before, and get a hyperimmune response. That was the problem with Denguevax.

lancet article.

Cumulative vaccine efficacy against virologically confirmed dengue was 64·2% in dengue-exposed participants and 53·5% in dengue-naive participants from first dose up to 4·5 years after the second dose.

lancet article link

article on NATURE from 2023

Is new dengue vaccine efficacy data a relief or cause for concern?

The exact immunopathogenic mechanisms of sequential heterotypic DENV infections are incompletely understood, but considerable evidence points to humoral and cellular adaptive immune responses occurring in response to the first infection facilitating increased DENV replication during the second infection which, in turn, drives pro-inflammatory cytokine secretion25,26,27,28,29,30,31. The exact number of annual dengue fatalities is not known but the estimates range between 5000 and 40,000 with many deaths occurring in children32,33.

with dengevax, the immune problem includes:>

Dengvaxia® Sanofi Pasteur licensed the first dengue vaccine (Dengvaxia®) in Mexico in 2015, and more than 20 countries thereafter, based on the safety and efficacy demonstrated in two phase III trials and a single season of disease surveillance. Unfortunately, the optimisim that a dengue vaccine was finally available quickly became disappointment when a safety signal was observed in vaccine recipients who were dengue non-immune at the time of vaccine administration44,45. In the third year of the phase III clinical trial, the youngest, non-immune vaccine recipients experienced increased rates of hospitalized and severe dengue compared to their unvaccinated peers

The next generation of dengue vaccines As expected, every dengue vaccine candidate following Dengvaxia® is being stringently reviewed for safety and efficacy in dengue immunes and non-immunes, across a broad age range of recipients, and for their ability to protect against the full spectrum of disease outcomes caused by infection with any DENV type. There is also a requirement for demonstrating safety and efficacy across more than one dengue season56,57,58.

Two new live attenuated dengue vaccines have now completed phase III efficacy trials and there is room for cautious optimism once again. Takeda recently received approval from Indonesia, European Commission, and Brazilian regulators for use of their two-dose vaccine (TAK-003) in people 4 years of age and older, regardless of baseline dengue immune status.

(https://www.takeda.com/siteassets/system/newsroom/2022/qdenga/ema-combined-h-5155-en.pdf) (accessed 21 January 2023).

https://butantan.gov.br/noticias/butantan%27s-dengue-vaccine-has-79.6-efficacy-partial-results-from-2-year-follow-up-show

In summary, the three live attenuated dengue vaccines which have generated clinical endpoint efficacy data have all demonstrated; (1) higher efficacy in dengue immune recipients; (2) higher efficacy against more severe clinical phenotypes; (3) variance in DENV type specific efficacy, and (4) the challenge of capturing data for all desired clinical endpoints (any dengue, severe dengue, hospitalized dengue), across all DENV-1–4 types, in both dengue immune and non-immune recipients.

one of the problem with attenuated virus vaccines is that sometimes the virus escapes and causes the disease (a major problem with the Oral Polio vaccine).

How to assess for the potential of vaccine-associated dengue is not straight forward. After two years of surveillance in the Butantan study there were no severe dengue cases nor cases with clinical warning signs. The Takeda experience, however, is more complex, and even though clinical and regulatory review committees for the European Commission and Brazil’s National Health Surveillance Agency (ANVISA) did not believe there was a safety signal in dengue non-immune recipients, this a point of contention

Conclusion It is clear the perfect dengue vaccine is not on the immediate horizon, but the Sanofi, Takeda, and Butantan/NIH/Merck experiences do inform us that it is possible to effectively immunize some people against disease scenarios that constitute dengue’s burden. I would contend when it comes to dengue countermeasure development, safety is non-negotiable, but all other expectations must be managed and considered in the aggregate. Our challenges with effectively communicating coronavirus disease 2019 vaccine performance characteristics should be a cautionary tale in this regard. Pursuit of the perfect dengue vaccine is a laudable goal, but not at the cost of overlooking imperfect options that could safely deliver tangible, albeit smaller scale, public health benefit.

I post the text and links etc so I can read these articles in detail on my tablet. QDenga page

hmmm...it says a lot about the politics of this vaccine that it has a long list of places for you to share the article, but X/twitter is not one of them.

just lie about your plans: Another covid deception

Deborah Birx from her memoir, explaining how "two weeks to flatten the curve" was just marketing for harsh, months-long lockdowns that she was really planning:

"On Monday and Tuesday [March 9th and 10th, 2020] … we worked simultaneously to develop the flatten-the-curve guidance…

— Kevin Bass PhD MS (@kevinnbass) February 15, 2025

gain of function on covid bat viruses 2015

link to Nature article:

Download PDF News Published: 12 November 2015 Engineered bat virus stirs debate over risky research Declan Butler

Lab-made coronavirus related to SARS can infect human cells. An experiment that created a hybrid version of a bat coronavirus — one related to the virus that causes SARS (severe acute respiratory syndrome) — has triggered renewed debate over whether engineering lab variants of viruses with possible pandemic potential is worth the risks.

In an article published in Nature Medicine1 on 9 November, scientists investigated a virus called SHC014, which is found in horseshoe bats in China. The researchers created a chimaeric virus, made up of a surface protein of SHC014 and the backbone of a SARS virus that had been adapted to grow in mice and to mimic human disease. The chimaera infected human airway cells — proving that the surface protein of SHC014 has the necessary structure to bind to a key receptor on the cells and to infect them.

italics mine 

It also caused disease in mice, but did not kill them.

Although almost all coronaviruses isolated from bats have not been able to bind to the key human receptor, SHC014 is not the first that can do so. In 2013, researchers reported this ability for the first time in a different coronavirus isolated from the same bat population2. The findings reinforce suspicions that bat coronaviruses capable of directly infecting humans (rather than first needing to evolve in an intermediate animal host) may be more common than previously thought, the researchers say. But other virologists question whether the information gleaned from the experiment justifies the potential risk. Although the extent of any risk is difficult to assess, Simon Wain-Hobson, a virologist at the Pasteur Institute in Paris, points out that the researchers have created a novel virus that “grows remarkably well” in human cells. “If the virus escaped, nobody could predict the trajectory,” he says. Creation of a chimaera

well well well. Italics mine. 

The argument is essentially a rerun of the debate over whether to allow lab research that increases the virulence, ease of spread or host range of dangerous pathogens — what is known as ‘gain-of-function’ research.

In October 2014, the US government imposed a moratorium on federal funding of such research on the viruses that cause SARS, influenza and MERS (Middle East respiratory syndrome, a deadly disease caused by a virus that sporadically jumps from camels to people).The latest study was already under way before the US moratorium began, and the US National Institutes of Health (NIH) allowed it to proceed while it was under review by the agency, says Ralph Baric, an infectious-disease researcher at the University of North Carolina at Chapel Hill, a co-author of the study. The NIH eventually concluded that the work was not so risky as to fall under the moratorium, he says/....

italics mine/.... here they note that the likelihood of such change in nature are small, and then the article goes on:

Baric and others say the research did have benefits. The study findings “move this virus from a candidate emerging pathogen to a clear and present danger”, says Peter Daszak, who co-authored the 2013 paper. Daszak is president of the EcoHealth Alliance, an international network of scientists, headquartered in New York City, that samples viruses from animals and people in emerging-diseases hotspots across the globe.

That is the group that funded these illegal risky experiments in the Wuhan lab. And it is the group that got money from the US Dept of Defense (not the HHS or NIH) to build a biolab here in the Philippines to search for such viruses. Luckily one of our leftie solons caught the DoD part and so the government refused to let them build it.

 https://www.usaspending.gov/award/ASST_NON_HDTRA12310006_9761

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