Why a Few People Develop Dangerous Dengue Infections

Have you ever wondered why only a few people develop dangerous Dengue infections?

“Patients with severe secondary disease have high levels of a particular type of antibody that triggers a forceful immune response. This distinctive signature did not show up in patients with more mild illness,” says senior author Jeffrey V. Ravetch, Theresa and Eugene M. Lang Professor and head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology.

“Our work sheds new light on the way in which the dengue virus co-opts antibodies produced as a result of the previous infection, using them to inflict more damage the second time around,” Ravetch adds.

Dengue virus image
Dengue virus image

Uncommon, but dangerous

Known as “breakbone fever” for the intense aches it causes, dengue is transmitted by mosquitos in the tropics and subtropics. In the more severe form of the disease, which typically occurs among people who have been infected before, patients can develop hemorrhagic fever, which causes them to leak fluid from their blood vessels and bleed abnormally, sometimes from the nose, gums, and under the skin. In extreme cases, people lose so much blood that they develop a critical condition known as shock.

Researchers have long thought this happens because, when it infects a second time, the virus somehow takes advantage of antibodies the immune system is still producing as a result of the first infection. But this doesn’t explain why less than 15 of percent people who catch dengue for the second time develop full-blown hemorrhagic fever or shock.

Previous work in Ravetch’s lab suggested differences in antibodies might account for why only some develop severe secondary infections. These Y-shaped proteins help the body defend itself against viruses and other intruders by latching onto infected cells with their arms. Meanwhile, their stems, known as Fc regions, bind to immune cells and tell them how to respond. Ravetch’s lab has shown that the structure of the Fc region can influence an immune response by, for example, promoting inflammation versus calming it.

An answer in architecture

For the current study, first author Taia Wang, then a postdoc in the lab, and her collaborators took a close look at the Fc regions of antibodies in blood collected from patients with mild and severe secondary dengue infections at Siriraj Hospital in Bangkok, Thailand. These people’s immune systems were still producing antibodies as a result of their first encounter with the virus, but the structure of these antibodies varied between individuals.

They found that the dengue patients with more serious disease had high levels of antibodies whose Fc regions lack a particular sugar, a variation known to strongly activate immune cells.

The researchers showed that activating signals from these antibodies aggravated the disease by leading to the destruction of blood-clotting cells called platelets. When their platelet levels plummet, patients bleed abnormally — a hallmark of hemorrhagic fever. The lower a patient’s platelet count, the more of these distinctive antibodies he or she tended to have.

“We found that some people’s immune systems respond to dengue infection by producing elevated levels of these pathogenic antibodies, which make them more vulnerable to a severe secondary dengue infection,” says Wang, who is now an assistant professor at Stanford School of Medicine. “It’s not yet clear if they produce more of these highly activating antibodies even before they encounter the virus.”

Ravetch and an international team of scientists identified a sign or signature of the misdirected antibodies that can lead to hemorrhagic dengue. The finding was published in the journal Science.

“So it can be a diagnostic tool,” he said. “We know who is at risk. We can see the patients coming in [to the hospital] with dengue fever and say, ‘Gee, you’re at risk to develop hemorrhagic fever. You can get really sick.’ So, we can take preventive measures. We can put you into a more intensive care-like environment. We can make sure your fluids are controlled. If we can do better care for these patients, you know, waiting for them to come in with shock.”

There is currently no treatment for severe dengue, only supportive care.

The discovery of this antibody signature could help fight the disease in a number of ways. “Because we now know what to look for, it may become possible to identify patients at risk of severe illness, so they can receive intensive, supportive care early on,” Ravetch says.

“It could also aid in the development of safe dengue vaccines that stimulate the immune system without triggering a secondary, potentially harmful response, and of new drugs designed to help patients recover by blocking the antibody signaling,” he adds.

From Rockefeller University..

My Dengue Story

My Dengue Story: It’s Not The Dengue That Sucks, It’s The Constant Comparison To Everybody Else’s Dengue

I got my dengue fever from the slum that houses the 101 India office. Yes, we work out of a slum. I’m typing this, Odomos-ed up, from a slum. I look out my window, and it’s a slum. The smell is of a slum, the sounds are of a slum (eee-oh-ay practise), it’s a slum. I go to the toilet, and it’s a slum toilet; “No poop, only pee” the sign reads, because I shit you not, in our slum, if you shit in the toilets, the toilets shit you back.

A whole new third world. A dazzling place I never knew

“How can you be so sure it was one of our slum mosquitoes,” my constipated Human Resources Manager argues.

Dengue fever – the worst two weeks of my life. It started with fatigue – sudden and overwhelming; I could barely move. I was running a slight fever as well. Most 101ers would have used this as an excuse to skip work. My amazing work ethic didn’t let me. Nothing keeps me from work my project manager. Three hours, two paracetamols, and zero attention (from said project manager) later, I was on my way home. My parents’ home. It was my mother’s birthday.

When it rains…

“Happy Birthday, Mama!” I greeted her at the door. “Get a dozen chicken patties,” she greeted me back, “we’re having guests.” A couple of hours later, halfway into my mother’s birthday dinner, my fever rose to a 104°. I was taken to the emergency room. “Let’s hope it’s not dengue,” a doctor with great bedside manner said. I hoped it was. Because while I was waiting for my test results, someone came in, dead on arrival. Death is a hard act to follow. I had to have more than just a fever.

So I had dengue. Illustration by Eshna Goenka

Platelet Count 2,00,000

“Go home,” they told me, “you don’t need hospitalisation.” They said the same thing to ‘dead on arrival’ too. How bad does one have to be to get a bed around here? But, it wasn’t my mother’s birthday anymore, so I did go home. I slept well knowing I’d wake up to pity, so much pity. People feeling sorry for me. Terminal illness privileges without the terminal illness.

But I woke up to this: 2 Lakh? Bro, my platelets were at 10,000! Why are you even home?

Platelet Count 1,40,000

I had 1,29,999 platelets to lose, and I had to do it quickly. The hospital seemed like the best place to  do it; they only had beds in the general ward.

The problem: 1 Lakh 40 Thousand? Bro, hit 5,000 and we’re talking.

The bigger problem: Caripill – Papaya extract pills. Even swallowers spit Caripill.

The biggest problem: Medical insurance doesn’t cover you unless your platelet count is below 1,00,000.

I had to get sicker.

Platelet Count 50,000

Success! I was nauseated, because of the Caripill. I couldn’t eat or stomach anything; not even the liquids I was told to sip on. The 10 IVs I was hooked on to all day weren’t helping my Worst Hunger Headache In The World.

I was sicker. Much, much sicker. Phew!

But are you bleeding from your orifices, bro? Clearly not, bro.

Platelet Count 35,000

I was finally moved out of the general ward. Not to a private room, but private-er, at least. A four-bed sharing room. My roomies were: a 90 y.o. ex-war veteran, a 70 y.o. family man, and a 35 y.o. who was admitted on his birthday. Every one of them was sicker than me. Bro, suck it up. Look at 90 y.o. uncle. So brave, fighting organ failure at this age…

I had to die.

Platelet Count 15,000

I was dying. Finally. I was also moved to a private room. Deluxe, FYI: Television, air conditioning, a desk, a view, hot water, thicker dal, more than one bhaaji, and a nun to come pray over me every morning. What a way to go.

A taste of my own medicine

I started bequeathing the little things I owned to the people I loved most – my Tazo collection to my kid brother, my tissue collection to my project manager, my laptop password to my creative director, and an inside joke for you, reader – but then…

Platelet Count 20,000

My platelet count was on the rise. As far as all my ex-dengued friends were concerned, I didn’t have dengue at all. ‘Tis but a scratch, bro. From 20,000, my platelet count rose to 50,000, to 1,00,000, to 2,10,000. I was discharged. I lost.

Save for a little weakness, and a backache that lasted me a couple of weeks, I came out all right. I’m a 100% now. I’m a 101% now. And back at 101. No battle scars, no pity-party bragging rights. I survived. And they celebrated my birthday before my birthday. Just in case I don’t last.

101 Dengue

1. Relax. Dengue’s not as bad as the news makes it out to be.

2. Hydrate. Sip on fluids as much as possible.

3. Water first, Caripill later. Wash your hands after you touch a Caripill.

4. You will have acidity, and you will have gas. Pass the gas. Nobody cares.

5. Don’t exert yourself. And if you do, don’t let your shortness of breath worry you.

6. If anybody asks about your platelet count, remember, it’s in the minus.

Disclaimer: The views expressed in this article are independent views solely of the author(s) expressed in their private capacity and do not in any way represent or reflect the views of 101India.com.

By Dominic S

Photographs by Dominic S

Subscribe to 101India

Spray Prevents Mosquito Reproduction

Spray Prevents Mosquito Reproduction

Credit: Wikimedia Commons.

Spray Prevents Mosquito Reproduction Can it halt the spread of dengue, malaria?

Though malaria infections have dramatically fallen since 2010, 91 countries and areas around the globe still have ongoing malaria transmission which causes half a million deaths annually. Moreover, the progress we’ve made so far risks becoming undone in face of rising insecticide resistance.  Luckily, humans are cleverer than mosquitoes, as one team from Harvard University recently demonstrated.

The researchers from the Harvard Chan School found that a non-toxic chemical can stop the spread of malaria just as effectively as insecticides.

Malaria is caused by the malaria parasite, Plasmodium falciparum, which is carried by Anopheles mosquitoes. When these mosquitoes were sprayed with a synthetic chemical called DBH (dibenzoylhydrazine), the females’ reproductive cycles became disrupted. DBH mimics the action of the steroid hormone  “20E” (20-hydroxyecdysone), which like estrogen in humans, plays a key role in the female mosquito’s reproductive cycle.

Experiments suggest the females which came in contact with the spray laid fewer eggs, didn’t mate successfully, and died faster than non-treated mosquitoes. The higher the DBH dose, the more pronounced the effects on the mosquitoes’ reproductive cycle. The DBH-treated mosquitoes were also less likely to be infected by Plasmodium f. 

The chemical was expelled both as a spray and in bed nets, with both methods proving equally effective at treating the mosquitoes. Because DBH is non-toxic, the chemical is not only suitable for use in bed nets where non-toxicity is of the essence but it’s also inert to other forms of wildlife or food crops.

“The study demonstrates the importance of basic research on mosquito biology for developing new tools against malaria,” said Caroline Buckee, co-senior author and assistant professor of epidemiology at Harvard Chan School.

“Modeling the impact of these effects on Anopheles population dynamics and Plasmodium transmission predicts that disrupting steroid hormone signaling using 20E agonists would affect malaria transmission to a similar extent as insecticides. Manipulating 20E pathways therefore provides a powerful new approach to tackle malaria transmission by the mosquito vector, particularly in areas affected by the spread of insecticide resistance,” the authors wrote in the journal PLOS Pathogens.

In 2015, nearly half of the world’s population was at risk of malaria. Most malaria cases and deaths occur in sub-Saharan Africa, and it is here that DBH might reap the most benefits. Before that happens, more tests are necessary before the chemical is deemed completely harmless to animals other than mosquitoes.

Truth About Zika?

 The Washington Post reports that, almost nine months after Zika was declared a global health emergency, the virus has infected at least 650,000 people in Latin America and the Caribbean, including tens of thousands of expectant mothers.

But to the great bewilderment of scientists, the epidemic has not produced the wave of fetal deformities so widely feared when the images of misshapen infants first emerged from Brazil.

Instead, Zika has left a puzzling and distinctly uneven pattern of damage across the Americas. According to the latest U.N. figures, of the 2,175 babies born in the past year with undersize heads or other congenital neurological damage linked to Zika, more than 75 percent have been clustered in a single region: northeastern Brazil.

The pattern is so confounding that health officials and scientists have turned their attention back to northeastern ­Brazil to understand why Zika’s toll has been so much heavier there. They suspect that other, underlying causes may be to blame, such as the presence of another ­mosquito-borne virus like chikungunya or dengue. Or that environmental, genetic or immunological factors combined with Zika to put mothers in the area at greater risk.

 

“We don’t believe that Zika is the only cause,” Fatima Marinho, director of the noncommunicable disease department at Brazil’s Ministry of Health, said in an interview.

Brazilian officials were bracing for a flood of fetal deformities as Zika spread this year to other regions of the country, Marinho said. However, “we are not seeing a big increase.”

Researchers and health officials remain cautious about the lower-than-expected numbers. The latest studies have found more evidence than ever that the virus can inflict severe damage on the developing infant brain, some of which may not be evident until later in childhood.

New York’s Aedes Mosquito Program

New York’s health department has and Aedes mosquito eradiction program and is investing in new technologies to halt the rapid spread of dengue fever in the densely populated city.

An Asian tiger mosquito. Credit: CDC/Wikimedia Commons                          Asian tiger mosquito: CDC/Wikimedia

If you haven’t spent a summer in New York you may not know how tropical its climate can be. Months of sultry heat and cloudbursts make mosquito outbreaks common. Mosquitos and mosquito-borne diseases have been part of New York life for centuries but the recent establishment of Aedes Aegypti has raised new problems.  Health department trucks have been spraying pesticide in the streets and flyers on street corners urge people to stay indoors.

New York Health Department has been using a mosquito “adulticide” this year: pesticides which kill flying insects rather than their larvae. It’s  usually done as a last resort when other methods have failed but this year, New York has been spraying aggressively to eliminate Aedes albopictus, a carrier of the Zika virus, and switching to a new insecticide that specifically targets Aedes.

Like Delhi, Singapore and Miami, New York is struggling to contain Dengue outbreaks caused by Aedes aegypti, the primary carrier for a host of viruses like chikungunya and Zika. Delhi’s chikungunya outbreak resulted in more than a thousand new cases reported last week. In New York, Aedes cousing, Aedes albopictus (aka Asian tiger mosquito) has not infected anyone yet but the health department is treating the mosquito like a disease carrier. NYHD announced a three-year, $21 million Zika prevention campaign and much of that is being spent on mosquito control. At a recent event, NYHD health commissioner Dr. Mary Bassett said, “We’re just trying to kill the Aedes mosquito.”

Aedes albopictus is known to carry more than 20 viruses and was responsible for a global chikungunya epidemic ten years ago. A native of Southeast Asia, it has spread far and wide and is on the list of 100 most invasive species on the planet. The Asian tiger was first discovered in the USA in a mosquito trap in a Memphis cemetery in 1983. Since then it’s spread to 40 states and today can be found as far north as Maine. Investigators suspect it arrived in the US in used auto tires from Japan or Taiwan.

Many New Yorkers have felt its bite at a backyard barbeque. “The entire metropolitan area is infested,” says Dr. Laura Harrington, Chair of the Department of Entomology at Cornell University. She and her students are  mapping Aedes albopictus spread in the Hudson valley and have been picking up dead mosquitos from back yards across Westchester County. Long, hot summers and unpredictable weather have contributed to the growth of the mosquito in the New York area, Harrington says.

NYHD is aware that mosquito-borne diseases can spread rapidly in densely populated urban areas (Aedes is an urban, indoor mosquito) and is experimenting with the novel the BG-Sentinel trap, which has  proven useful in capturing Aedes and tracking mosquitoes in their natural habitat like back yards, cemeteries and public parks. A collapsible, fabric container the size of an ice bucket, it releases ammonia, lactic acid and a  chemical cocktail that mimic the scent of human skin. The New Yorker says the traps “smell like a hot subway car during rush hour.” The traps’ contents, a heap of dead mosquitoes, are sent to a public health lab where they are tested for the presence of Zika virus.

NYHD made a user-friendly mosquito map based on tracking data with  orange dots marking Aedes hotspots and blue dots for the Culex mosquito (West Nile virus carrier). The department is sharing this information with the public for the first time this year. The northern Queens neighbourhood of College Point, which was “ground zero” for the West Nile epidemic of 1999,  has the highest mosquito counts because local wetlands and marshes are an ideal breeding ground for Culex but now there are signs that the Asian tiger presence is growing. “I’ve picked lots of Aedes in College Point,” says Dr. James Cervino, a Queens-based marine biologist who’s been examining neighborhood mosquitoes in as part of his research on climate change. Queens, he says has a number of  “blighted areas” with thriving mosquito populations and the interactive map hotspots are just the tip of the iceberg.

Forested and swampy areas in Queens, Brooklyn, the Bronx and Staten Island are the focus of mosquito control efforts early in the season. Ponds and lakes are treated with larvicide dropped by helicopter.

Because Aedes albopictus hides in tree holes and stumps, sprayed insecticides which kill adult mosquitoes are less effective in there . The new pesticides this year may help overcome this.  Duet (the commercial name for the pesticide) has an added an ingredient, which acts as an irritant to draw mosquitoes out of their hard-to-reach spots and forces them to fly around. Once airborne, the mosquito comes in contact with an ultra-low volume spray of a synthetic pyrethroid called sumithrin, which kills them on contact. Duet was tested at the Center for Vector Biology at Rutgers University and found to be almost  100% effective on a sample of Asian Tiger mosquitoes from New Jersey.

New York has the largest outbreak of Zika cases in the US: 599 people have the disease, tough all contracted the virus overseas. Mayor Bill de Blasio pointed out that the city is home to a large Caribbean and Latin American community: “Right now, the central challenge is people who bring it back”.  Pregnant women are urged not to travel to these regions as the virus can cause severe birth defects including microcephaly. In some Bronx immigrant neighborhoods the virus is already a concern. “We have quite a few cases of pregnant women from the Dominican Republic with Zika.” said Dr. Tammy R. Gruenberg, an obstetrician at the Women’s Health Pavilion at Morris Heights Health Center.  Doctors there have been handing out prevention kits to pregnant women planning trips to a Zika-affected countries. The kit contains insect repellent spray, condoms and two donut-shaped “dunks” that kill mosquito larvae in standing water.

With temperatures dropping, the threat of locally transmitted Zika in New York is dropping but the Asian tiger mosquito is still a concern. To truly defeat Aedes, Laura Harrington feels big cities cannot just rely on larvicides and pesticides: “We’ve been spraying for decades. We need new ways to target mosquitoes, safer insecticides and rapid development of vaccines.”

 

Dengue Zika Mosquitoes

The Dengue mosquito is aedes aegypti and the zika mosquito is aedes albopictus, usually called ‘The Asian tiger mosquito’Aegypti feeds mornings and evenings, while albopictus feeds during the day. This is the dengue mosquito, Aedes Aegypti:

Dengue Pandemic Vector
Dengue Pandemic Vector

The Asian tiger mosquito particularly bites in forests during the day, so has been known as the forest day mosquito. This is Aedes Albopictus:

Aedes Albopictus the Zika Mosquito
Aedes Albopictus the Zika Mosquito

It takes an expert to tell the difference!

Depending upon region and biotype, activity peaks differ, but for the most part, they rest during the morning and night hours. They search for their hosts inside and outside of human dwellings, but are particularly active outside. The size of the blood meal depends upon the size of the mosquito, but it is usually around 2 μl. Their bites are not necessarily painful, but they are more noticeable than those from other kinds of mosquitoes. Tiger mosquitoes generally tend to bite a human host more than once if they are able to.[22][24]

Ae. albopictus also bites other mammals besides humans, as well as birds.[22][24] The females are always on the search for a host and are persistent but cautious when it comes to their blood meal and host location. Their blood meal is often broken off before enough blood has been ingested for the development of their eggs, so Asian tiger mosquitoes bite multiple hosts during their development cycle of the egg, making them particularly efficient at transmitting diseases. The mannerism of biting diverse host species enables the Asian tiger mosquito to be a potential bridge vector for certain pathogens that can jump species boundaries, for example the West Nile virus.

Here’s a video explaining the two mosquitoes’ habits:

Dengue Health Insurance?

Holy cow, now we’ve got dengue health insurance!

Dengue Mosquito Net: insurance?
Dengue Mosquito Net: insurance?

“We have now moved into digital under the overall ambit of protection focus that we have. We could have easily gone digital with a term plan or ULIPs. That was not our idea of going digital. We wanted to use a very relevant product as our strategy to go digital”, Anoop Pabby, Managing Director & CEO, DPLI told Business Line here.

DHFL Dengue Shield is an affordable Dengue Insurance Policy with premium as low as ₹ 1 per day. It is fixed benefits policy and no detailed bills at the time of claim.

An individual has the option to choose sum insured from ₹ 25,000 to ₹ 50,000. Options of both Single and annual premium payment exist in Dengue Shield where a customer can enjoy a discount of up to 21 per cent on Single Premium payment.

Pabby also said that group version of Dengue Shield would soon be available.

DPLI has signed an agreement with Itz Cash to provide customer awareness about Dengue Shield through their 20,000 plus retail touch points in Delhi for the initial phase.

Meanwhile, Pabby said that DPLI was aiming at a new business premium of ₹ 1,000 crore this fiscal. This aim represents 36 per cent increase over new business premium of ₹ 736 crore recorded in 2015-16.

srivats.kr@thehindu.co.in

Dengue Shock Syndrome

What is Dengue Shock Syndrome?

Dengue Shock Syndrome is a collection of symptoms resulting from a dengue infection. Its symptoms – including hemorrhaging – resemble those you’d see after an accident, when someone is ‘in shock’. Typically, older children or adults suffer 2–7 days of high fever and show two or more of the following symptoms:

  • severe headache,
  • retro-orbital eye pain,
  • myalgias,
  • arthralgias,
  • a diffuse erythematous maculo-papular rash, and
  • mild hemorrhagic manifestation.
  • Subtle, minor epithelial hemorrhage, in the form of petechiae, are often found on the lower extremities (but may occur on buccal mucosa, hard and soft palates and or subconjunctivae as well), easy bruising on the skin, or the patient may have a positive tourniquet test.
  • Other forms of hemorrhage such as epistaxis, gingival bleeding, gastrointestinal bleeding, or urogenital bleeding can also occur, but are rare.
  • Leukopenia is frequently found and may be accompanied by varying degrees of thrombocytopenia.
  • Children may also present with nausea and vomiting.
  • Patients with DF do not develop substantial plasma leak (hallmark of DHF and DSS, see below) or extensive clinical hemorrhage.
Dengue virus image
Dengue virus: Dengue Shock Syndrome

Serological testing for anti-dengue IgM antibodies or molecular testing for dengue viral RNA or viral isolation can confirm the diagnosis, but these tests often provide only retrospective confirmation, as lab results are typically not available until well after the patient has recovered.

Clinical presentation of DF and the early phase of DHF are similar, and therefore it can be difficult to differentiate between the two forms early in the course of illness. With close monitoring of key indicators, the development of DHF can be detected at the time of defervescence so that early and appropriate therapy can be initiated.

The key to successfully managing patients with dengue infection and lowering the probability of medical complications or death due to DHF or DSS is early recognition and anticipatory treatment(For more detailed guidance on management for DF please see the recommended treatment courses for DHF in the links listed below.)

Dengue Hemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS): The third clinical presentation results in the development of DHF, which in some patients progresses to DSS. Vigilant is critical for identifying warning signs of progressing illness and early symptoms of DHF which are very similar to those of DF. Case Definitions Page

There are three phases of DHF:

  1. the Febrile Phase;
  2. the Critical (Plasma Leak) Phase; and
  3. the Convalescent (Reabsorption) Phase.

The Febrile Phase: Early in the course of illness, patients with DHF can present much like DF, but they may also have hepatomegaly without jaundice (later in the Febrile Phase). The hemorrhagic manifestations that occur in the early course of DHF most frequently consist of mild hemorrhagic manifestations as in DF. Less commonly, epistaxis, bleeding of the gums, or frank gastrointestinal bleeding occur while the patient is still febrile (gastrointestinal bleeding may commence at this point, but commonly does not become apparent until a melenic stool is passed much later in the course). Dengue viremia is typically highest in the first three to four days after onset of fever but then falls quickly to undetectable levels over the next few days. The level of viremia and fever usually follow each other closely, and anti-dengue IgM anti-bodies increase as fever abates.

The Critical (Plasma Leak) Phase: About the time when the fever abates, the patient enters a period of highest risk for developing the severe manifestations of plasma leak and hemorrhage. At this time, it is vital to watch for evidence of hemorrhage and plasma leak into the pleural and abdominal cavities and to implement appropriate therapies replacing intravascular losses and stabilizing effective volume. If left untreated, this can lead to intravascular volume depletion and cardiovascular compromise. Evidence of plasma leak includes sudden increase in hematocrit (≥20% increase from baseline), presence of ascites, a new pleural effusion on lateral decubitus chest x-ray, or low serum albumin or protein for age and sex. Patients with plasma leak should be monitored for early changes in hemodynamic parameters consistent with compensated shock such as increased heart rate (tachycardia) for age especially in the absence of fever, weak and thready pulse, cool extremities, narrowing pulse pressure (systolic blood pressure minus diastolic blood pressure <20 mmHg), delayed capillary refill (>2 seconds), and decrease in urination (i.e., oliguria). Patients exhibiting signs of increasing intravascular depletion, impending or frank shock, or severe hemorrhage should be admitted to an appropriate level intensive care unit for monitoring and intravascular volume replacement. Once a patient experiences frank shock he or she will be categorized as having DSS. Prolonged shock is the main factor associated with complications that can lead to death including massive gastrointestinal hemorrhage. Interestingly, many patients with DHF/DSS remain alert and lucid throughout the course of the illness, even at the tipping point of profound shock. CDC:

Doctors: See case definition for DHF and DSS. Adobe PDF fileExternal Web Site IconThere are no good videos about dengue shock syndrome, but this text video might help:

Dengue Bribery in Philippines?

Was there Dengue bribery in Philippines? Questions hover over Asia’s first dengue vaccination program in Philippines.

Dengue Mosquito
Dengue Mosquito: Asian Tiger

The Aedes aegypti mosquito carries the dengue virus, Zika virus, and other mosquito-borne illnesses as it travels from person to person.

Asia’s first dengue vaccine has been distributed in a mass school-based immunization program in the Philippines. So far, the program appears to be running without difficulties, but some health professionals are concerned that the vaccine was released before researchers could ensure its long-term safety.

From the beginning, the vaccine’s French manufacturer Sanofi Pasteur has been concerned about a potential problem with the vaccine — that while it could help prevent dengue initially, it could later increase the severity of the disease, according to Dr. Antonio Dans, a professor at the University of the Philippines College of Medicine.

“The real dengue we are afraid of is severe dengue, not the mild ones,” Dans said in a statement. “If a vaccine prevents mild disease but causes severe dengue, we shouldn’t be using it at all.”

This possibility is being monitored by the vaccine’s developer, Dans said in a news release; and since the phenomenon may happen a full three years after immunization occurs, it will take some time to study the vaccine’s long term effects.

However, as the virus infects as many as 400 million people annually, the vaccine for dengue has been awaited with increasing impatience. In an effort to stem the spread of the virus in regions heavily burdened by the disease, the WHO recommended that the drug be introduced in dengue-endemic sites while awaiting prequalification.

According to the organization, the WHO is now waiting on an application from the vaccine’s manufacturer.

The vaccine, Dengvaxia, has also been registered in Mexico, Brazil and El Salvador. Now, the Philippines — which in 2015 saw an almost 60 percent increase in dengue cases from the year prior — has become the first to make the vaccine commercially available.

“This initiative sends a strong message to the rest of the … world that dengue vaccination is a critical addition to integrated disease prevention efforts,” according to a statement from the vaccine’s developer Sanofi Pasteur.

The official launch of the school-based immunization program on April 4 sidestepped a prequalification procedure by the WHO, as is standard for new vaccines to ensure safety and effectiveness. This raised additional concern from some medical professionals, according to Philippine media network GMA, who say the immunization program should not have skipped the prequalification process, especially considering such limited knowledge of the vaccine’s long-term side effects.

Still, the company said the Dengvaxia vaccine, which took 20 years and $1.8 billion to develop, should prevent 80 percent of dengue-related hospitalizations and up to 93 percent of cases of severe hemorrhagic dengue fever. The vaccine is designed for people ages 9 to 45, and is administered in three separate doses over a six-month period.

Since the start of the immunization program last month, Dengvaxia has been administered to more than 200,000 grade-school students in the capital city of Manila. Of 17,000 people who were injected with the vaccine in the Philippines in February as part of the clinical study, just 27 developed side effects, Health Undersecretary Vicente Belizario told reporters.

According to Health Minister Janette Garin, the $103 million program aims to administer the first dose of the vaccine to 1 million children by June.

The history of developing a vaccine for dengue has been wrought with challenges. An effective vaccine must protect against four closely related viruses that can cause the disease, and researchers have had limited understanding of how the virus affects the immune system. Among other barriers making vaccine development more difficult, there are no easily measurable sign (such as antibodies) that a person is immune to the disease.

The WHO estimates that dengue fever, the world’s most common mosquito-borne virus, infects an estimated 390 million people around the world each year. So far this year, more than 33,000 dengue cases have been recorded in the Philippines alone. Read more…

 

India’s Botanical Dengue Drug

India’s botanical Dengue drug is getting world wide attention. At last! India, the home of ayurvedic medicine, has begun work to develop, test and market a botanical drug to treat of dengue, with drug major Sun Pharma announcing its collaborative effort with the International Centre for Genetic Engineering and Biotechnology (ICGEB).
The move follows a March announcement of success in the drug’s initial development stage through a joint project between the ICGEB, the Department of Biotechnology (DBT).

Dengue Mosquito: Aedes Aegypti
Dengue Mosquito: Aedes Aegypti

Sun Pharma will fund entire development programme of Cissampelos pariera (Cipa), the botanical drug to treat all strains of dengue. While the pharma giant will pay royalty following commercialisation of the drug, the ICGEB will provide the technical know-how and pre-clinical expertise.
“Using the knowledge of traditional Indian medicine, we explored the indigenous herbal bio-resource to identify plants with pan-DENV inhibitory activity and identified CIPA as a safe, affordable and effective solution,” said Dr Dinakar M Salunke, director, ICGEB, New Delhi.
Given the densely-populated cities and the high prevalence of the mosquito that spreads dengue — aedes aegypti — India is home to close to 50% of the global population estimated to be at risk of dengue. Severe dengue, which can potentially kill, correlates with very high-virus load, reduction in platelet counts and haemorrhage.
The new drug is expected to reduce high-virus load and make the disease milder, leading to fewer hospitalisations. The collaboration aims to explore how the extract prepared from Cipa Linn can inhibit the replication of virus in living cells against dengue infection.
The terms of this agreement permits Sun Pharma’s access to all the intellectual properties of this drug cross 17 countries.
“In tropical countries like India, where dengue outbreaks are significantly intense, a drug for dengue is an unmet public health need. Our partnership with ICGEB aims to develop Cipa as a safe, effective & affordable botanical drug for treatment of dengue,” said Kirti Ganorkar, senior V-P, business development and portfolio management, Sun Pharma, the world’s fifth largest generic pharmaceutical company.
The ICGEB will establish assay systems for development of Cipa for treatment of dengue infection for a pre-defined period of time. The ICGEB will work exclusively with Sun Pharma for the development of this drug, and clinical treatment strategies based on botanical and phyto-pharmaceuticals. Sun Pharma will pay royalties on sales post commercialisation. Other financial details of this agreement are confidential.
Dengue is estimated to costs India over $1.1 billion (about Rs 7,260 crore) annually, with the cost of medical care being nearly $550 million and the indirect cost, in terms of lost wages, being another $550 million. Read more..