Category: Vector-Borne Disease

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

by pragmaticsolidarity, posted in APHA IH Section, Vector-Borne Disease

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.

Malaria-2015 and beyond

by abbhirami, posted in APHA IH Section, Vector-Borne Disease

One of the mosquito-borne illness (we have been hearing about these a lot lately in the news, heard of Zika virus anyone?) that the global community has been trying to eradicate for a long time now is malaria. Malaria is caused by Plasmodium, a parasitic protozoan, that is transmitted from the bites of infected female anopheles mosquitoes.

Early this month, the WHO released a video describing the progress that has been made toward reducing/eradicating malaria globally and the challenges that exist in the fight against malaria. The disease is widespread in Sub-Saharan Africa, Asia and Latin America. 214 million cases were reported in 2015. A multi-pronged approach of coordinated responses that include timely diagnosis through Rapid Diagnostic Testing (RDT), treatment using artemisinin-based combination therapy (ACT), distribution of long-lasting insecticide-treated bed nets (LLIN) and targeted insecticide spraying, the global mortality rates have decreased by 60% between 2000-2015. The malaria incidence rates also fell by 37% between 2000 and 2015.

Childhood mortality due to malaria fell by 65% worldwide and by 71% in Africa. This is particularly impressive and an important win since children under five years of age are highly susceptible to malaria infection and death.

In 2015, the global burden of malaria is highly concentrated in 17 countries, mostly in Africa and progress in reducing malaria incidence in these high burden countries has lagged behind other countries.
These data thus far are dramatic and encouraging but given the many challenges including poorly functioning health systems, climate change and global economy, a coordinated, multi-pronged global response with continued investment is needed. The Global Technical Strategy for Malaria was approved by the WHO in 2015. This strategy follows the timeline of the sustainable development goals and aims to reduce both malaria incidence and mortality by 90%. The framework provided in the technical strategy consists of 3 pillars, that could be used as a foundation for anti-malaria strategies and programs. The three pillars are a) ensure universal access to malaria prevention, diagnosis and treatment; b) accelerate efforts towards elimination and attainment of malaria-free status; and c) transform malaria surveillance into a core intervention. The framework aims to provide clear defined paths to achieve the lofty goals of malaria reduction and elimination.

Now is the time for consistent financial support from national governments and other donors to keep the momentum going in our fight against malaria. Together we can end malaria!