Dengvaxia’s FDA Priority Review: Is the global health community settling on a Dengue vaccine?

The Food and Drug Administration (FDA) announced on October 30th that Dengvaxia’s, Sanofi Pasteur’s dengue vaccine, file has been accepted for priority review within the regulatory agency. With this announcement, the FDA will ensure that a decision will be declared on approval in the United States within six months for the world’s first licensed vaccine protecting against this flavivirus. While this declaration by the FDA displays an improved pragmatic approach to addressing neglected tropical diseases (NTDs), this vaccine has created controversy throughout the global health community. This vaccine is licensed in twenty countries to date and implemented into country wide vaccination programs. However, the concerns accompanying this recombinant, live, attenuated, tetravalent dengue vaccination have led to a discontinuation of this technology with a loss of confidence in several nation states. The Philippines, the first country to complement their vaccination program with this vaccine, has even instructed Sanofi to reimburse the $70 million the country spent to vaccinate 830,000 children. This has caused many global health experts to doubt the impact this vaccine can have throughout the world – causing many to wonder if the global health community is settling on a dengue vaccine.

The dengue virus is estimated to cause 400 million infections each year spanning each of the World Health Organization’s (WHO) regions. This arbovirus belongs to Flaviviridae family and is spread to humans through the bite of an infected female Aedes aegypti mosquito and to a lesser extent from the Aedes albopictus species. The dengue virus has four unique serotypes, DEN-1, DEN-2, DEN-3, and DEN-4, which has caused an effective vaccine to be eluded for centuries. When a person is infected with one certain serotype, the person gains life-long immunity to that serotype. However, if that person contracts a different serotype, it increases the risk of the person developing severe dengue. This phenomenon is called antibody-dependent enhancement (ADE) which allows the different serotype to enter cells more efficiently due to the previously created antibodies from the initial serotype. The symptoms that dengue causes depend on primary or secondary infection. Primary infection results in an acute febrile illness that is typically cleared by the immune system within seven days, while secondary infection can lead to dengue hemorrhagic fever or dengue shock syndrome causing serious morbidity and mortality. The dengue virus currently has no approved treatments – highlighting the importance of an effective and safe vaccine for children and adults alike.  

The significant setbacks for Dengvaxia first arose when Sanofi Pasteur released interim studies concerning children aged 2 to 16 receiving the vaccine who were seronegative. This information was released on November 29, 2017 and revealed that among dengue-seronegative participants, recipients had increased rates of hospitalization for virologically confirmed dengue (VCD) and severe VCD in the vaccine group than in the group not administered the vaccine. These risks were significantly elevated in patients who were aged 2 to 8 years of age and became evident earlier than those aged 9 to 16 years of age. When this data became available, it led to the Strategic Advisory Group of Experts on Immunization (SAGE) of the WHO to reconvene and update their guidance on Dengvaxia. On April 18, 2018, SAGE recommended that for countries considering implementing Dengvaxia, every individual should be screened to determine their serological status with only seropositive persons receiving the vaccine.

The flavivirus genus includes other NTDs including the Zika virus, Japanese Encephalitis, West Nile Fever and Yellow Fever in addition to the Dengue Virus. The symptoms of each these ailments can present almost identically, especially in their milder forms, seeming almost flu-like in nature. When considering these identical disease presentations and the WHO’s recommendation to prescreen individuals for Dengvaxia, health care professionals must turn to dengue serological testing to ensure best practice – if the vaccine is accidentally given to a person with, for example, the Zika virus with no previous case of dengue due to a misdiagnosis from medical history, this would increase the risk of morbidity and mortality if dengue was contracted subsequently. The gold standard for serological testing is isolation and characterization of the virus, like PCR; however, this typically takes six or more days to receive the results and can be burdensome with it’s cost on a public health care system. A more common approach is enzyme immunoassay (ELISA) which is cost effective and less time consuming. However, in areas where two or more of the aforementioned flaviviruses exist, there is IgG cross reactivity between the viruses causing false positives for the dengue virus when ELISA is used. This often rules out the use of ELISA due to a common vector, Aedes aegypti, being able to spread two or more of these viruses within the same zone. Since the dengue virus is endemic throughout the developing world, dedicated health care professionals in these areas often don’t have funds, technology, or training in order to utilize the gold standard, PCR, in dengue testing — further highlighting the health disparities that exist on this earth. This leaves a major barrier to giving proper care to a large portion of humanity including administering this vaccine safely.

With the addition of rapid, accurate dengue test for the serological status of individuals that is in the pipelines (although no estimate of how soon it will be developed has been released yet), this vaccine will certainly find its niche in the global health society. However, this niche will exclude an enormous percentage of humans that would benefit from a safe and effective dengue vaccine. Those individuals that are currently seronegative and those who don’t have access to well-funded public health care system will continue to be at risk for developing the fatal consequences of the dengue virus. Global health leaders need to continue to promote and demand a vaccine that will ensure protection for a greater majority of people. Although this vaccine will serve some well, health care professionals must not settle until the dengue virus and each neglected tropical disease is properly addressed.

Global Health Weekly News Round-Up

  • National HIV testing day is Wednesday.

Politics and Policies

  • Health care proposal gives Louisiana more Medicaid spending flexibility.
  • Azerbaijan can prohibit abortion.

Programs

  • U.S. forces support anti-malaria health campaign in Africa.
  • Commonwealth to tackle non-communicable disease in West Africa. Meetings will explore plans to deal with NCD’s such as diabetes, cardiovascular diseases and chronic respiratory diseases.
  • Scientists at the University of Saskatchewan have teamed up with researchers in Ethiopia and Kenya in the two innovative projects to help deliver safer and more nutritious food in Africa through better plant breeding and soil management and a state-of-art vaccine for cattle.
  • McCann Health pledges to help end preventable child deaths; joins USAID’s new public-private partnership. It has announced $5 million commitment of in-kind resources and technical assistance to accelerate progress towards ending this problem.
  • United Nations and its partners have made a global appeal for $1.6 billion to provide humanitarian relief to Nigeria, Burkina Faso, Mali, Mauritania, Chad, Niger, Cameroon, Gambia and Senegal.
  • The United Nations Children’s Fund (UNICEF) office in Gambia has recently supported the government of Gambia to respond to the severe malnutrition of children, by providing highly nutritious products.
  • DHL (Gambia office) donates 150 cartons of long lasting insecticide treated mosquito nets (LLINS) to the Ministry of Health and Social Welfare as a part of contribution towards the fight against malaria in this country.
  • The government and donors have finalized plans for a Sh400 million cancer treatment and chronic diseases center in Eldoret (Kenya).
  • Council of Ministers in South Sudan has approved U.S. $173 million to construct 100 health units.
  • The Global Fund has resumed support to Zambia with a $100 million grant to help the country to fight AIDS.
  • India to receive Rs 20 crore healthcare grant from Norway to improve rural health services to further reduce child and maternal mortality.
  • Recall stops New Zealand tuberculosis vaccinations.

Research

  •  The scientists from the University of Cambridge Metabolic Research Laboratories at the Institute of Metabolic Science, UK, have found the genes responsible for a disease in which parts of the body grow disproportionately. They found this disorder was linked to a mutation that drives cell growth.
  • According to recent study done by the researchers from Glasgow outdoor physical activities like walking, running, biking had a 50 percent greater positive effect on mental health than going to gym. They found that the activities through green space lowered the stress level.
  • A study published recently describes the biodiversity and epidemiology of drug-susceptible and drug-resistant tuberculosis in Ibadan, Nnewi and Abuja, using 409 DNAs extracted from culture positive TB isolates.
  • A research published in BMC Public Health by the researchers from the London School of Hygiene and Tropical Medicine indicates global weight gain more damaging than rising numbers. They say if the increasing levels of fatness are replicated globally it could mean the equivalent of an extra billion people on the planet.
  • A study brings forward unwanted pregnancy and associated factors among the pregnant married women in Hosanna town in Southern Ethiopia.
  • A survey named as ‘Integrated Biological and Behavioral Surveillance among Migrant Female Sex Workers in Nairobi’ indicates that female sex workers from Somalia have a little knowledge about the deadly HIV/AIDS.
  • A new research at MIT could improve the ability of untrained workers to perform basic ultrasound tests, while allowing trained workers to much more accurately track the development of mental conditions such as the growth of a tumor or the buildup of plaque in arteries.
  • A study indicated that the oral health status of patients with mental disorders in Southwest Ethiopia is poor. There is a need to impart education about the oral hygiene to them.
  • A study shows how easily pandemic H5N1 bird flu could evolve. Their main conclusion was that this virus can acquire the ability of aerosol transmission between mammals. Mutations as low as 5 (but certainly less than 10) are sufficient to make H5N1 virus airborne.
  • A study reveals that the teens that spend more time indoors in front of screens are more likely to feel lonely and shy, while those who spend their time outdoors are much happier.
  • Study shows that the genetically modified cows produce healthier milk. This milk can be consumed by the lactose intolerant people. One more study shows that this milk contains healthy fat like that found in fishes. Chinese have produced this milk which has same properties as human breast milk.
  • A study suggests that cauterization of a peculiar population of stem-like sells in a part of cervix when infected by human papilloma virus can be a method of prevention of this deadly infection.
  • A team of scientists in Singapore have discovered a human antibody that can kill the dengue virus within two hours.
  • According to a study, to reduce the diabetes risk we should eat slowly.

Diseases and Disasters

  • Two fatal cases of Vibrio vulnificus infection investigated in Hong Kong.

Global Health Weekly News Round-Up

  • April 7th is celebrated every year as World Health Day to mark the founding anniversary of World Health Organization (WHO).

Politics and Policies:

  • Food and Drug Administration (FDA) warns against Japanese weight loss pills. The product contains a suspected cancer-causing agent – Phenolphthalein.
  • Indonesia has won a tobacco dispute with the United States after the World Trade Organization (WTO) ruled in its favor saying that the US ban on clove cigarettes was discriminatory.
  • The 126th Inter-Parliamentary Union (IPU) Assembly in Kampala, Uganda, adopts Resolution on “Access to Health as Basic Right”.
  • World politicians meeting in the capital of Uganda, Kampala, have agreed on the need to repeal laws discriminating against HIV/AIDS which they say have contributed to an increase in the rate of new infections.
  • Dharamsala (in India) based Central Tibetan Administration (CTA) has launched a Medicare system for Tibetans in Exile.
  • The Department of Health (DH) of Hong Kong has appealed the public not to buy or consume an oral product called “Ling Zhi She Xiang Tong Mai Dan”.
  • The Chilean Senate has rejected three bills that would have eased the country’s absolute ban on abortions.

Programs

  • An emergency funding of $26 million has been authorized by President Barack Obama to the United Nations High Commissioner for the Sudanese refugees. This will help to respond to the crisis of health, water and food.
  • Bill Gates- Backed Alliance prepares to fight cervical cancer in the developing world. This program is planned to protect 20 million women in thirty countries by the end of decade.
  • Palmcroft Church of Arizona is organizing a campaign to raise thousands of dollars to bring clean water to the poorest of poor in Haiti and Ethiopia.
  • United States Fund for UNICEF President and CEO, Ceryl Stern joins Royal delegation to UNICEF emergency center.
  • The Kenya Aids Vaccination Initiative (KAVI) is collaborating with Uganda, Rwanda, Zambia, Tanzania, South Africa and Gambia to carry out its research to develop biological marker for understanding the diseases among the people in Africa.
  • The Arab bank for Economic Development in Africa (BADEA) has signed loan agreements worth US$ 10 million to improve health services and expanding its coverage in West African region.
  • A meeting organized by the interest groups together for a Stakeholders Consultation on Tuberculosis in the mining sector under the auspices of the South African Development Community (SADC), with the World Bank support.
  • The Primate’s World Relief and Development Fund (PWRF) and the Canadian International Development Agency (CIDA) will together begin US$ 10.8 million health care program that will focus on maternal and child health in fifty nine villages in Burundi, Mozambique and Tanzania.
  • The HIV Early Infant Diagnosis Project funded by the Clinton Foundation and Mozambique’s Ministry of Health has saved an estimated 20,000 babies from infection in the first six months of its launch. Sequoia Technology and Telit Wireless Solutions- providers of technology for this project- has developed a way for the rural medical clinics in Africa to wirelessly receive HIV test results of the expectant mothers within days of testing.
  • The UK government is planning to develop a smartphone natural disaster application, to help victims of flood, famines and earthquake.
  • The first Czech clinic of addictology, focused on the treatment and prevention of alcohol and illegal drug addictions and research into them was opened in Prague.

Research

  • Researchers say that fish along the Orange County coast may have been affected by radioactivity that fell in California in the days after Japan’s 2011 nuclear disaster. They also say that small levels of radioactive isotope have accumulated in seaweed along the local shoreline.
  • A research suggests link between an injectable form of progestin-only birth control and an increased risk of breast cancer.
  • A universal cancer vaccine has been developed by a group of researchers. The early clinical trial has shown that it triggers an immune response and targets a molecule found in 90% of all cancers.
  • A remedy consisting of phytonutrients extracted from eggplant have been confirmed to treat and basal cell and squamous cell carcinoma.
  • A study on females in China revealed that the vegetables like mustard and turnip greens, bok choy, cauliflower and green cabbage are protective against breast cancer.
  • According to a study malaria stain resistant to the most effective drug used to treat the disease has spread along the Thai-Myanmar border. If ways are not found to contain it, it might reach India and Africa.
  • According to a recent survey Delhi (in India) has the highest number of corporate employees afflicted with insomnia due to high stress level and demanding schedules in offices. This city is followed by Mumbai, Ahmedabad, Chandigarh, Hyderabad, Pune and Chennai.
  • Type 2 diabetes rising sharply in China. About 30 percent increase in cases in only seven years.
  • Data from 2010 Basic Health Research (Riskesdas) shows that 27.1% of obese people above the age of eighteen years with BMI greater than 27.The same data shows obesity among kids below five years olds has increased to 14% from 11% in 2007.
  • Scientists from Duke-NUS Graduate Medical School in Singapore and the National Cancer Center Singapore have identified more than 600 genes that are mutated in stomach cancer, the second most lethal cancer in the world.
  • The blood-pressure medication prazosin was found to be an effective treatment to curb nightmares related to post-traumatic stress disorder (PTSD).
  • A study shows that most of the fat people think they are not fat.
  • Researchers have demonstrated the effectiveness of hypnotism in reducing severe symptoms of Irritable Bowel Syndrome.
  • A new study suggests a link between obesity during pregnancy and autism.
  • The dengue virus may make mosquitoes even thirstier for human blood according to a study conducted at the John Hopkins Bloomberg School of Public Health.
  • According to a new study, waist size helps to predict heart disease risk in teenagers.

Diseases & Disasters

  • The eastern horn of Africa is in famine crisis. About 750,000 people are at a risk of death.
  • H1N1 was detected in a Hong Kong’s slaughter house during regular influenza virus surveillance for pigs.
  • Avalanche in Siachen glacier region claims life of people in India and Pakistan.
  • Nine miners trapped in collapsed mine in Peru.