User:Projectdengue/controlling the Disease of the Future

PHP 2013: Controlling the Disease of the Future
Dengue is the World's most important arbovirus with 2.5 billion people at risk globally and estimates of 100 million infections annually, 2 million of which develop into dengue hemorrhagic fever, a more severe form of the disease, resulting in 21,000 deaths. The disease is caused by four serotypes,meaning re-infection is possible, making control harder. A vaccine preventing infection from all serotypes is needed.

Epidemiology
The dengue virus is mainly vectored by the mosquito, Aedes aegypti and due to increasing urbanization and populations, dengue epidemiology is fast evolving: expanding and increasing outbreak frequency. Unsatisfactory sanitisation and water storage, within urban areas allow for proliferation of the Aedes mosquito and thus increased spread of the virus. The maximum burden of dengue is borne by the Asia-Pacific Region, approximately 1.8 billion (over 70%) of the 2.5 billion individuals at risk globally, reside there. Dengue also has the potential to re-establish in areas such as the United States.

Infection with any of the four serotypes (DEN 1–4) leads to dengue fever. While recovery from an infection of one serotype provides life-long immunity against that serotype, it does not protect against the others. During the infection, presence of maternally acquired heterologous antibodies or those from a previous infection, increase the risk of severe disease (dengue haemorrhagic fever and dengue shock syndrome). Therefore, recovery from an infection with one serotype, means a secondary case is likely to be worse.

Recently a vaccine admixture (TV003) has been developed and undergone trials, entering further clinical development and evaluation. TV003 induced a trivalent or greater neutralizing antibody response in 90% of flavivirus-naive adult vaccinees. With such positive results the vaccine has been licensed for in-country production and use by manufacturers in multiple countries.

Global burden of disease
Dengue is one of the World Health Organisation's 17 neglected tropical diseases. Its incidence has increased 30-fold in the past 50 years. Annual estimates suggest up to 50-100 million infections occur in over 100 endemic countries, therefore nearly half of the world's population is at risk. Dengue is also spreading and has been found in: the Middle East and the states of Texas and Hawaii. This spread increases the need for an effective control programme.

Current funding situation
As one of the 17 neglected tropical diseases, funding for dengue is very limited. Internationally the funding for dengue prevention and control is very limited and the increasing funding gap between dengue and other dieases affects outbreak preparedness and response. The baseline disease burden of dengue in South-East Asia is approximately 0.42 DALYs (Disability-Adjusted life year) per 1000 population, of which 52% is due to premature mortality and 48% to acute morbidity. The baseline cost of treatment is US$99 per 1000 population per year.

Controlling the Disease of the Future
As funding is so poor for dengue, £1 billion would greatly benefit the development and distribution of a vaccine, which can provide lifelong immunity and reduce dengue's significant impact.

Background
Vector control appears incapable of giving long term protection against dengue, let alone eradicating it. Therefore Controlling the Disease of the Future aims to tackle dengue using a large-scale vaccination programme. With vaccine candidates in later trials and having shown positive early results (trivalent or greater antibody response in 90% of candidates) this programme appears possible. Due to the large scale spread of the disease the project aims to target the Pacific South-East, namely Cambodia, Indonesia, Philippines and Vietnam due to feasibility, endemicity, large populations and where financial constraints limit large-scale programmes.

Justification
Despite prolonged efforts for effective vector control in dengue and other diseases, such as Malaria, evidence suggests that community-based control programmes, alone and in combination, only very weakly control dengue, particularly as mosquitoes become insecticide resistant. On the other hand vaccines are showing promising results and have been licensed for production and in-country use in Brazil, Vietnam and India.

Proposal
The project aims to control the spread of the disease through a multi-year immunising programme of all 15 month old infants through existing immunization schedules. In total this would lead to 10,760,000 vaccination per year, (10% adjusted to account for error) if 100% coverage is achieved. While achieving 100% coverage is practically impossible and vaccines are not 100% effective, aiming for it gives a higher feasibility to achieving the 70% coverage necessary for herd immunity.

By working with current programmes the cost and logistics of a new initiative are greatly reduced, 15 months was chosen as this is the age of measles vaccination. Furthermore, the severe cases of dengue (shock syndrome and haemorrhagic fever) are more common in the under-fifteens and most individuals are immune to a majority of the serotypes by age fifty. The vaccine has been costed at 22p (needle, syringe and drug, in a multidose vial), and through further examination non-vaccination costs have been estimated at £9.38. . This is likely to be an overestimate, due to saving through utilising pre-established programmes. A budget of £1 Billion will fund this programme for ten years, by which time it will be possible to analyse results and implement further steps.

Due to the vaccine still being in trial stages there will be a time lag of 1-2 years before large-scale vaccination could be implemented. However this gives time to coordinate with the governments and set up the logistics, including ensuring manufacturing capabilities are present. If further problems were encountered it is hopeful that another vaccine could be implemented, as multiple candidate vaccines now exist,.

Goals
The overall aims of the project are to see a yearly reduction in the number of dengue cases in the four target countries, within the vaccinated group. Over a ten year period it is is hoped that the majority of the most vulnerable group will become immune and therefore cases should drop significantly, particularly the most severe ones. At the end of the period, it is hoped that further funding will be secured to continue the programme and roll it out across other countries.