Tag Archives: global health

New vaccine shows protection against aerosol tuberculosis infection in monkeys

The new tuberculosis vaccine MTBVAC takes a new step as a candidate for universal vaccination against tuberculosis and an alternative to the current Bacillus Calmette–Guérin (BCG) vaccine, according to the results of the research published in the journal NPJ-Vaccines which shows the protection results of the MTBVAC vaccine compared to the current BCG vaccine in a model of respiratory tuberculosis in rhesus macaques.

The currently used BCG vaccine, based on a live attenuated form of Mycobacterium bovis isolated from cows and which, this year 2021, will make a 100 years since its first use in humans as a tuberculosis vaccine, continues to be the only licensed vaccine against the disease. After decades of research in this field, MTBVAC is the first and only vaccine based on the human pathogen Mycobacterium tuberculosis that has entered human clinical evaluation, a historic milestone in human vaccinology.

MTBVAC has shown its safety in Phase 1 studies in adults in Switzerland and in Phase 1b in newborns in South Africa, where Phase 2 studies are currently being carried out in tuberculosis-infected and uninfected adults and in healthy newborns to select the dose and study its safety and immunogenicity in a larger number of participants in order to support advanced Phase 3 efficacy evaluation in the target age-groups.

MTBVAC is the first and only live attenuated vaccine based on a human isolate of Mycobacterium tuberculosis designed and constructed by the research groups of Carlos Martin of the University of Zaragoza and of Brigitte Gicquel of Institut Pasteur in Paris

In this recently published study led by Dr. Sally Sharpe from Public Health England, a single dose of the MTBVAC vaccine administered intradermally has been found to confer significantly better protection against aerosol exposure to M. tuberculosis in Rhesus macaques when compared to BCG by the same route and dose of administration. Vaccination with MTBVAC resulted in a significant reduction in disease pathology induced by M. tuberculosis infection as measured by medical scan imaging in vivo, macroscopic pathological lesions examination, and pathological anatomy study of the frequency and severity of pulmonary granulomas.

This study consolidates previous preclinical and clinical safety and immunogenicity studies and represents a strong proof of concept of the efficacy of MTBVAC in the macaque model, the most relevant model of efficacy against respiratory tuberculosis, supporting and urging the clinical development of studies to demonstrate the efficacy of MTBVAC as a prophylactic vaccine against respiratory tuberculosis in humans. This would make MTBVAC an essential tool in the fight against tuberculosis.

Despite WHO’s declaration of tuberculosis as “global health emergency” in 1993, today the disease continues to be one of the leading causes of mortality caused by infectious diseases worldwide. The WHO Global tuberculosis report 2020 estimates that 1.4 million people died of tuberculosis in 2019 and it is estimated that as a consequence of the COVID-19 pandemic deaths from tuberculosis could increase by up to twenty per cent (20 %) in the next five years.

Measles infected 10 million, claimed over 142,000 lives last year

After decades of progress against measles, the highly contagious yet vaccine-preventable disease is making a slow and steady comeback. The World Health Organization (WHO) and the U.S. Centers for Diseases Control and Prevention said in a new report that there were nearly 10 million cases of measles and 142,000 deaths, with outbreaks on every continent.

“Our finding is that in 2018, there’s been an increase in both the cases and the deaths that have occurred from measles,” Dr. Kate O’Brien, director of WHO’s immunization program, said in a video release. “In other words, we’re backsliding.”

Poor vaccination coverage and large pockets of unvaccinated children have resulted in devastating measles outbreaks in many parts of the world – including in countries that had high coverage rates or had previously eliminated the disease. In some cases, conflict, security or a breakdown in services are making it hard to reach children in remote or hard-to-reach areas. In others, parents are not vaccinating their children due to complacency, mistrust or misinformation about vaccines. This year, for example, the United States reported its highest number of cases in 25 years, while four countries in Europe — Albania, Czechia, Greece, and the United Kingdom — lost their measles elimination status in 2018 following protracted outbreaks.

Samoa and the Asia Pacific

The latest region to be affected is Asia Pacific, where measles is being reported even in places where the disease had been eliminated such as Australia, Japan, and New Zealand. In Samoa, the Government has declared a state of emergency, and all schools are temporarily closed. According to the latest data released by the Government, measles had already claimed 63 lives, mostly young children.

More than 4,300 cases have been reported among a relatively small population, and new cases are being reported daily. According to estimates from UNICEF and WHO, vaccination coverage in Samoa plummeted from 58 percent in 2017 to just 31 percent in 2018, largely due to misinformation and mistrust among parents.

Five countries account for almost half of measles cases in 2018

Democratic Republic of the Congo (DRC): Immunization services have been hampered since 2018 because of poor infrastructure, violence and insecurity, attacks on health centers, lack of access to healthcare, shortages of vaccines and lack of trust in health workers.

The situation has further deteriorated in 2019, with more than a quarter of a million people infected this year alone, more than three times the number of measles cases in 2018 and more than the number of cases and deaths attributed to Ebola in the country. Most of the 5,000 reported deaths so far this year were among children under five. UNICEF has provided the Ministry of Health with 8 million doses of bundled measles-containing vaccines, and distributed over 1,300 medical kits – containing antibiotics, rehydration salts, Vitamin A and other medicines – to all affected health zones to treat children with complications.

Liberia: The outbreak began in 2017 due to low vaccine coverage. In 2018, the country had recorded the highest number of cases, with outbreaks reported in 5 out of 15 counties, and recorded about 3,948 suspected cases including 16 deaths. The recurrent outbreaks continued through 2019, even though the number of cases has declined.

Madagascar: From August 2018 to November 2019, there were 244,607 cases of measles, and 1,080 died due to measles, of which 91 percent were children under 14 years old. Although the rate of new cases is significantly decreasing, some districts are still reporting cases. UNICEF has helped purchase 8.7 million doses of measles vaccine and supported the government to distribute these vaccines at the local level.

Somalia: In 2018, low vaccination coverage, and crowded living conditions created ideal conditions for the spread of measles and other vaccine-preventable diseases. The number of cases has substantially reduced this year compared to 2018, thanks to immunization campaigns supported by UNICEF and partners of the Measles & Rubella Initiative.

Ukraine: Since the start of the outbreak in 2017, over 115,000 people have been infected with 41 deaths, including 25 children. In 2018 alone, there were over 54,000 cases and 16 deaths. Cases remained at alarming levels in 2019. Over 58,000 cases were registered until 6 November 2019, with 20 deaths. UNICEF has increased its support to the Ministry of Health to vaccinate more children by training health care workers and promoting vaccines. UNICEF has also provided support to accelerate routine immunization across the country and address vaccine hesitancy.

In the Americas, Brazil listed 11,887 cases, most of which were reported in Sao Paulo. Two outbreaks in New York state in the US have been declared over, though the WHO says other outbreaks are occurring throughout the country.

Measles is among the most infectious diseases and can be prevented with two doses of vaccine. Even with the implementation of routine immunization, measles continues to circulate globally due to sub-optimal vaccination coverage and population immunity gaps. Any community with less than 95% population immunity is at risk for an outbreak. If an outbreak response is not timely and comprehensive, the virus will find its way into more pockets of vulnerable individuals and potentially spread within and beyond the affected countries. As long as measles continues to circulate anywhere in the world, no country can be assured to avoid importation. 

New vaccine is incredibly efficient at preventing typhoid

Caused by the bacterium Salmonella Typhi, typhoid is a major cause of fever in children in low- and middle-income countries and is responsible for nearly 11 million cases and more than 116,000 deaths a year worldwide.

It is usually spread through contaminated food or water. Once Salmonella Typhi bacteria are eaten or drunk, they multiply and spread into the bloodstream. Symptoms include prolonged high fever, fatigue, headache, nausea, abdominal pain, and constipation or diarrhoea. Some patients may have a rash. Severe cases may lead to serious complications or even death. Salmonella Typhi lives only in humans.

In 2018, the World Health Organization (WHO) recommended the introduction of typhoid conjugate vaccine (TCV) for infants and children over six months of age in typhoid-endemic countries, and added it to its list of pre-qualified vaccines.

Prior to TCV, two vaccines have been used for many years to protect people from typhoid fever, an injectable vaccine based on the purified antigen for people aged over 2 years and a live attenuated oral vaccine in capsule formulation for people aged over 5 years. These vaccines do not provide long-lasting immunity and are not approved for children younger than 2 years old.

Although TCV has been shown to protect against the disease in studies involving healthy volunteers in the UK, no efficacy studies in endemic populations had been completed. Now, the Typhoid Vaccine Acceleration Consortium (TyVAC), which includes researchers from the University of Oxford, the University of Maryland School of Medicine, and PATH has completed a large field study in Nepal and published the interim analysis in the New England Journal of Medicine.

The study involved 20,000 children aged 9 months to 16 years of age, who were randomly given one of two vaccines: half received TCV and half received the Group A meningococcal (MenA) vaccine – the latter acted as the control group.

Blood tests showed that typhoid occurred in 7 participants who received TCV and 38 receiving Men A vaccine. The researchers noted that these were preliminary results, and that the study will continue to follow-up the participants for two years.

Dr. Andrew Pollard, Professor of Paediatric Infection and Immunity at Oxford University’s Department of Paediatrics, said: “This is the first study to show that a single dose of TCV is safe, immunogenic, and effective, which provides clear evidence that vaccination will help efforts to control this serious disease and is a strong endorsement of the WHO policy for vaccine implementation.”

“The efficacy of these results in an endemic population adds to a growing body of evidence supporting the use of TCV to reduce disease and save lives in populations that lack clean water and improved sanitation,” said Dr. Kathleen Neuzil, MD, MPH director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine and director of TyVAC.

These results show the vaccine has the potential to significantly reduce the burden of typhoid in high-risk populations. This is especially timely with the recent spread of extensively drug-resistant typhoid, which threatens child health in affected regions.

Pakistan’s current typhoid outbreak is the first-ever reported outbreak of ceftriaxone-resistant typhoid and represents an alarming trend in the spread of drug-resistant typhoid. Not only is the strain resistant to ceftriaxone, the standard treatment in many parts of the world, but it is also resistant to most antibiotics commonly used for typhoid, making it increasingly challenging and costly to treat.

TCVs have the potential to overcome many of the challenges that impeded uptake of earlier vaccines, including longer-lasting protection, fewer doses, and suitability for children under two years of age, allowing for inclusion in routine childhood immunization programs.

Measles cases spike globally with a 26% increase from last year

The World Health Organization (WHO) on Wednesday released an update on global measles cases, noting a spike in the number of cases confirmed.

As of Nov. 5, there were more than 440,200 measles cases worldwide reported to WHO, a 26% increase from 350,000 cases in 2018. In 2017, the World Health Organization (WHO) reported 110,000 measles deaths globally, mostly among children under the age of five. The potentially deadly illness, which can be easily prevented with vaccinations, continues to spike globally, with multiple large outbreaks being reported across Africa, Europe, Latin America and the Middle East.

DR Congo posts huge numbers

The most shocking numbers were posted in the Democratic Republic of Congo (DRC), which registered a total of 250,270 cases on November 17, an increase of 8,000 cases over the week prior. Some 5,110 measles-related deaths were registered in the DRC. Elsewhere in Africa, Chad reported 25,596 cases as of November 17, affecting 94% of the country’s districts. Whereas the DRC is currently issuing vaccinations, Chad has yet to do so.

© UNICEF/Thomas Nybo
A nurse prepares to vaccinate an infant during a regularly-scheduled immunization clinic in North Kivu province, Democratic Republic of the Congo

Outbreaks in every corner of the world

In the Americas, Brazil listed 11,887 cases, most of which were reported in Sao Paulo. Two outbreaks in New York state in the US have been declared over, though the WHO says other outbreaks are occurring throughout the country.

Paul Martinka | Bill de Blasio and Dr. Oxiris Barbot during a press conference

In Europe, Ukraine far outpaced other countries, reporting some 56,802 cases, followed by Kazakhstan with 10,126 cases, Georgia with 3,904 cases, Russian Federation with 3,521 cases, Turkey with 2,666 cases, and Kyrgyzstan with 2,228 cases of measles. Some of these outbreaks (e.g. Georgia, Russian Federation, Turkey) have resolved.

A measles epidemic in Samoa has killed 39 people, with the WHO blaming an anti-vaccine messaging campaign for leaving the Pacific island nation vulnerable to the spread of the virus. The UN health agency warned that a steep decline in vaccination rates in Samoa had paved the way for a “huge outbreak”, with almost 3,000 in a country of just 200,000 people.

Measles is among the most infectious diseases and can be prevented with two doses of vaccine. Even with implementation of routine immunization, measles continues to circulate globally due to sub-optimal vaccination coverage and population immunity gaps.

Any community with less than 95% population immunity is at risk for an outbreak. If an outbreak response is not timely and comprehensive, the virus will find its way into more pockets of vulnerable individuals and potentially spread within and beyond the affected countries. As long as measles continues to circulate anywhere in the world, no country can be assured to avoid importation. 

Scientist Ian Mackay, who specializes in virology at the University of Queensland, said the rhetoric peddled on social media was “not correct”. Some claim a suggested alternative to getting vaccinated is high doses of Vitamin A, which experts say cannot prevent getting the measles infection and is not based on evidence. “The only way to prevent getting measles — the disease — is to have the vaccine, and have both doses of it,” he said.

“No other personal medications or vitamin concoction or magical oil will prevent that virus from spreading. It’s only vaccination.”

The World Health Organisation’s Nikki Turner said online misinformation claiming children could be treated with vitamins had “no scientific evidence” behind them, and that such claims were “conning” people from getting correct treatment, the Samoa Observer reported last week.

Polio Type 3 eradicated globally

Humanity has eradicated another enemy (after smallpox in May 1980, and rinderpest or ‘cattle plague’ in October 2010). The independent Global Commission for the Certification of Poliomyelitis Eradication (GCC) has declared wild poliovirus type 3 to be globally eradicated. Announced on World Polio Day, this is a major milestone in the global effort to eradicate all poliovirus strains and ensure that no child will ever again be paralyzed by any poliovirus anywhere.

“This achievement is another giant step towards freeing the world from the crippling disease. The WHO European Region has massively contributed to this since it was declared polio free in 2002,” says Dr Nedret Emiroglu, Director of Health Emergencies and Communicable Diseases, WHO/Europe. “However, despite progress, there is still much left to be done across the globe. Continued work to reach every last child with the polio vaccine, strengthening routine immunization and surveillance, and ensuring safe containment of polio viruses, will be key to keeping polio at bay and protecting the gains achieved.”

Type 2 has been gone since 1999 leaving only Type 1, in Pakistan and Afghanistan. But vaccine resistance there has led to 88 cases so far this year, after only 33 all last year. So while the defeat of Type 3 is a welcome success, the WHO is still calling polio a Public Health Emergency of International Concern – and the emergency is now reaching a crunch point. “We face a very hard twelve months,” says Dr Michel Zaffran, director of polio eradication for the World Health Organization.

That isn’t only due to problems in Pakistan. The Type 2 vaccine virus replicates rapidly in humans, provoking strong immunity which is one of the reasons why wild Type 2 polio has long been wiped out while the other two types persisted.

The oral polio vaccine (OPV) contains an attenuated (weakened) vaccine-virus, activating an immune response in the body. When a child is immunized with OPV, the weakened vaccine-virus replicates in the intestine for a limited period, thereby developing immunity by building up antibodies. During this time, however, the vaccine-virus is also excreted and in areas of inadequate sanitation — this excreted vaccine-virus can spread in the immediate community (and this can offer protection to other children through ‘passive’ immunization), before eventually dying out. On rare occasions, if a population is seriously under-immunized, an excreted vaccine-virus can continue to circulate for an extended period, allowed to survive and mutate. In very rare instances, the vaccine-virus can genetically change into a form that can paralyse – this is what is known as a circulating vaccine-derived poliovirus (cVDPV).

Since 2017, circulating vaccine-derived poliovirus has caused more cases of paralysis than the actual wild poliovirus. To address this challenge, the entire world switched to a live vaccine with only polio Types 1 and 3 in 2016. Kids born since 2016, however, can transmit outbreaks of Type 2 vaccine virus, because they have not been given the live Type 2 vaccine.

There have been more outbreaks than predicted in 2016: ten in Africa this year, including countries such as Zambia, China and the Philippines. In the Philippines, a massive polio vaccine campaign was recently launched with community health workers and volunteers going door-to-door to give kids droplets of the oral vaccine. After being polio-free for almost two decades, polio is back in the Philippines. 

Philippine Health Secretary Francisco Duque III, second from left, administers anti-polio vaccine to a child during the launch of a campaign to end the resurgence of polio Friday, Sept. 20, 2019 at suburban Quezon city, northeast of Manila, Philippines. Philippine health officials declared a polio outbreak in the country on Thursday, nearly two decades after the World Health Organization declared it to be free of the highly contagious and potentially deadly disease. (AP Photo/Bullit Marquez)

The outbreaks can be stopped with live, type 2 vaccines, says Zaffran. The problem is that it seeds more reverted vaccine virus. A novel Type 2 vaccine virus, genetically modified to be even less likely to revert, might be the solution to the vaccine-derived poliovirus dilemma. Earlier this year, virologists in Antwerp reported that the vaccine was safe, well-tolerated, and successfully induced immunity in 30 people – who were isolated for a month in a custom-built “poliopolis” that kept the virus from escaping. Further trials are being done but the new vaccine virus is already being used by an Indonesian firm, Biofarma, to make live Type 2 vaccine.

Another challenge is donor fatigue. “We know that the last mile has proved to be the toughest phase of eradication,” says Zaffran. The Global Polio Eradication Initiative (GPEI) is now seeking $3.27 billion for its next four years of work, with a donor “pledging moment” scheduled for November 19 in Abu Dhabi.

A 10% increase in dog vaccination reduces human deaths by 12.4%

Rabies is a virus that is usually spread by a bite or scratch from an infected animal. The virus attacks the central nervous system and can cause inflammation in the brain, eventually leading to death. In principle, no human today should die from rabies, and yet rabies is responsible for an estimated 59,000 human deaths and over 3.7 million disability-adjusted life years (DALYs) lost every year.

That total is not as high as the death toll from tuberculosis, HIV/AIDS, and malaria; but, unlike those diseases, rabies seems able to infect all and every mammal species we know of. Dogs, the predominant host in most regions, can become infected from any rabid wild animal, and then infect humans. 

The World Health Organization has made it a goal to eliminate human rabies deaths due to dog bites by the year 2030. An increase in dog rabies vaccination rates decreases dog rabies cases, human exposure, and human deaths, according to a new article in PLOS Neglected Tropical Diseases.

Implementing the goal of rabies elimination requires understanding the complex interaction between dog rabies vaccinations and human risk and response. Between 1995 and 2005, there was a rapid decline in dog and human rabies cases in seven Latin American countries following investments in both dog vaccination programs and human post-exposure prophylaxis (PEP) use.

New research by investigators from the School of Economic Sciences and the Paul G. Allen School for Global Animal Health at Washington State University, analyzed data from those seven countries — Brazil, Colombia, Peru, Venezuela, Nicaragua, Dominican Republic and Mexico. The data, compiled from reports published by the Reunión de Directores de los Programas de Rabia de las Américas (REDIPRA) from 1995 through 2006, included rates of dog vaccinations, dog rabies cases, reported human exposures, human PEP use, and human rabies cases.

The researchers found that a 10% increase in dog rabies vaccination rates decreases cases of dog rabies 2.3%. They add that this leads to a decline in how often humans are exposed to cases of rabies. At the same time, however, the reported number of cases of rabies stays constant or even increases — as more people report exposure to the same infected animal “which may result from higher rabies awareness due to anti-rabies campaigns,” the team notes.

While human exposures decline as dog rabies cases decline, exposures per dog rabies case increase, likely due to increased awareness. In addition, a 10% increase in dog vaccination leads to a 2.8% decrease in PEP use, and each 10% increase in PEP use decreases human deaths by 7%. Overall, a 10% increase in dog vaccination reduces human deaths by 12.4%.

“The findings highlight the critical importance of mass dog vaccination, heightened public awareness, treatment access, and the use of clinical algorithms to reduce both false negatives leading to death and false positives leading to costly unnecessary PEP prescriptions,” the researchers say.

World Rabies Day, observed on September 28 every year, aims to raise awareness about rabies prevention as well as highlight progress in defeating this horrifying disease. The day also marks the death anniversary of Louis Pasteur, the French chemist and microbiologist, who developed the first rabies vaccine.

How to prevent dementia, according to new WHO guidelines

Dementia refers to the decline in mental ability that is severe enough to impair a person’s ability to perform everyday activities. It affects memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgement. Around 50 million people worldwide have dementia with Alzheimer’s disease as the most common type. And every year brings 10 million new cases, says the report recently released by the World Health Organization (WHO).

“In the next 30 years, the number of people with dementia is expected to triple,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus. “We need to do everything we can to reduce our risk of dementia. The scientific evidence gathered for these guidelines confirms what we have suspected for some time, that what is good for our heart, is also good for our brain.”

Age is a risk factor so the older you are, the more likely you are to develop dementia. Certain genetic factors are involved with some more unusual forms of dementia — for the most part, dementia develops as a combination of genetic and “environmental” factors (i.e. smoking, lack of regular exercise). Although age is the top risk factor, “dementia is not a natural or inevitable consequence of aging,” the report says.

The report outlined what in WHO’s expert opinion think will and won’t help reduce the risk of dementia. So, if you want to save your brain, here are the do’s and don’ts from the new WHO guidelines for preventing dementia.

The DO’s

Exercise. The role of exercise is especially important. A physically active lifestyle is linked to brain health. A recent study of more than 1,600 people over age 65 found that those who spent more time sitting had the same risk of developing dementia as people who carry a genetic mutation that puts them at higher risk of Alzheimer’s. Weight loss could indirectly reduce the risk of dementia by improving a variety of metabolic factors linked with cognitive impairment and dementia (i.e. glucose tolerance, insulin sensitivity, blood pressure, oxidative stress, and inflammation).

Continue Learning. You’ve heard the saying: “use it or lose it.” Studies show that those who utilize their brains more by learning a new language or musical instrument, or furthering their education tend to have lower rates of dementia and problems with their thinking later in life.

Eat well. A healthy diet contains fruits, vegetables, legumes, nuts, and whole grains. In particular, committing to a Mediterranean diet (plant-based cooking, little meat and a heavy emphasis on olive oil) could help. The Mediterranean diet is the most extensively studied dietary approach, in general as well as in relation to cognitive function. Several systematic reviews of observational studies have concluded that high adherence to this diet is associated with decreased risk of mild cognitive impairment and Alzheimer’s Disease, but modest adherence is not.

Socialize. Socialization is important for all of us. Engaging with other people in social situations help patients suffering from Alzheimer’s disease and other forms of dementia and may even slow the progress of these conditions. The Lancet Commission on Dementia Prevention, Intervention, and Care identified social engagement as an intervention that could be used to prevent dementia

Lower Blood Pressure. Lowering blood pressure may help protect memory and thinking skills later in life. A large blood pressure study, called Systolic Blood Pressure Intervention Trial, or SPRINT, looked at over 9,000 people over the age of 50 years old and found that those who lowered their blood pressure to 120 (systolic blood pressure) were 19 percent less likely to develop cognitive impairment. Results were published in the Journal of the American Medical Association (JAMA).

The DON’TS

Don’t Smoke. There is strong evidence that smoking is associated with an increased risk of dementia. The toxins in cigarette smoke increase oxidative stress and inflammation, which have both been linked to developing of Alzheimer’s disease. Tobacco cessation is associated with reduced depression, anxiety and stress, and improved mood and quality of life compared with continuing to smoke.

Don’t drink too much. Excessive alcohol consumption leads to numerous health problems such as liver damage, stomach issues, impaired cognitive function, and more. If alcoholic beverages are consumed in large quantities over a relatively short period of times, most health problems can be cured relatively easily using special treatment and by quitting drinking. However, if one abuses alcohol throughout many years, this doesn’t only lead to liver cirrhosis, but also a condition called alcoholic dementia. There is extensive evidence on excessive alcohol as a risk factor for dementia and cognitive decline.

Don’t waste money on supplements. There is currently no evidence to show that taking supplements (i.e. B vitamins, antioxidants, omega-3 ginkgo) reduces the risk of cognitive decline and dementia. In fact, scientific evidence shows that in high doses these supplements may be harmful.

These potentially modifiable risk factors mean that prevention of dementia is possible through a public health approach, including key interventions that delay or slow cognitive decline or dementia. Much of the WHO’s advice is common sense and aligns with what the US National Institute on Aging advises.

Dengue vaccine candidate looks promising in Phase 3 Trial

Yellow fever is spread by mosquitos. Image credits: James Gathany.

Dengue is a mosquito-borne disease that causes flu-like symptoms but can be lethal and kill up to 20% of those with severe dengue. In the last five decades, dengue has spread from being present in a handful of countries to being endemic in 128 countries, where about four billion people live. WHO has listed dengue as one of the top global health threats in 2019 alongside Ebola, global flu pandemic, HIV, antimicrobial resistance and many others.

Dengue cases have also increased 30-fold in this time period. In addition, more people are traveling than ever before and millions of travelers to endemic areas are also at risk of being bitten by the disease-carrying mosquitoes. A high number of cases occur in the rainy seasons of countries such as Bangladesh and India. Now, its season in these countries is lengthening significantly (in 2018, Bangladesh saw the highest number of deaths in almost two decades), and the disease is spreading to less tropical and more temperate countries such as Nepal, that have not traditionally seen the disease. An estimated 40% of the world is at risk of dengue fever, and there are around 390 million infections a year.

There is no specific treatment for dengue fever. For severe dengue, medical care by physicians and nurses experienced with the effects and progression of the disease can save lives – decreasing mortality rates from more than 20% to less than 1%. Maintenance of the patient’s body fluid volume is critical to severe dengue care.

(FILES) This file photo taken on April 4, 2016 shows a nurse showing vials of the anti-dengue vaccine Dengvaxia, developed by French medical giant Sanofi, during a vaccination program at an elementary school in suburban Manila.

The first dengue vaccine, Dengvaxia® (CYD-TDV) developed by Sanofi Pasteur was licensed in December 2015 and has now been approved by regulatory authorities in 20 countries for use in endemic areas in persons ranging from 9-45 years of age. In April 2016, WHO issued a conditional recommendation on the use of the vaccine for areas in which dengue is highly endemic as defined by seroprevalence of 70% or higher. In November 2017, the results of an additional analysis to retrospectively determine serostatus at the time of vaccination were released. The analysis showed that the subset of trial participants who were inferred to be seronegative at time of first vaccination had a higher risk of more severe dengue and hospitalizations from dengue compared to unvaccinated participants.

A new vaccine, TAK-003, is based on a live-attenuated dengue serotype 2 virus. Preliminary data through 15 months (Part 1 of the trial) showed that the vaccine met the primary efficacy endpoint of preventing virologically-confirmed dengue fever induced by any of the four dengue serotypes. In addition, the vaccine was found to be well-tolerated with no significant safety concerns.

“We are excited to publish the data in a peer-reviewed journal as quickly as possible,” said Rajeev Venkayya, MD, and President at Takeda. Part 2 of the trial will evaluate secondary outcome measures including vaccine efficacy by serotype, baseline serostatus and severity; long-term safety and efficacy evaluation (an additional 3 years) will be included in the third part of the study.

Takeda expects to file for licensure once Part 2 of the study is complete in each of the eight countries where its clinical trial took place: Brazil, Colombia, Panama, Dominican Republic, Nicaragua, Philippines, Thailand and Sri Lanka. The company plans to file in the U.S. and Europe within a year of filing in dengue-endemic countries, Venkayya said. Takeda and dengue experts are already planning ways to review the latest vaccine data with those regulators.

The Global Dengue & Aedes-Transmitted Diseases Consortium (GDAC), a group funded in part by drugmakers that works closely with WHO, scheduled a meeting for early March in Bangkok with regulators from at least six countries to take a first look at Takeda’s results, said Dr. In-Kyu Yoon, director of GDAC.