Asia has been endemic for dengue for some time. And by following the World Health Organization (WHO) guidelines, Asian countries have made some significant advances in the fight against the disease. Indonesia, for example, has reduced its case fatality rate from 41% in 1968 (when dengue was first reported) to 0.9% in 2013.
But despite the improved case management, integrated vector control and community participation, the incidence of dengue across Asia is still too high, and spreading very fast.

Eagerly awaiting a dengue vaccine

Prof Sri Rezeki Hadinegoro, paediatrician and senior lecturer at the Dr Cipto Mangunkusumo hospital in Jakarta, hopes the introduction of a dengue vaccine will dramatically reduce the incidence and mortality of dengue across Asian endemic countries. “We are eager to add it to our dengue control and prevention strategy here in Indonesia,” she adds.
The long awaited dengue vaccine has recently made a gigantic leap closer. The analysis into the efficacy and interim long-term safety of Sanofi Pasteur’s dengue vaccine candidate has been made available. Published in The New England Journal of Medicine with the title “Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease” (Hadinegoro et al.), the study pools and analyses data across three clinical trials in dengue-endemic countries within the Asia-Pacific and Latin America.

CYD14 Indonesian Study Team, image courtesy Sri Rezeki Hadinegoro

93.2% protection against severe dengue

As one of the study’s authors, Prof Hadinegoro discussed its results with us. “The pooled study results showed consistently higher efficacy for preventing symptomatic dengue and an acceptable post-vaccination safety profile for individuals aged nine and older,” she reveals. “For this age group the results showed the vaccine provided 65.6% protection against symptomatic dengue of any severity and 93.2% protection against severe dengue. They also showed that it prevented 80.8% of dengue hospitalizations during the 25-month follow-up period.”
Prof Hadinegoro explained the importance of protecting the pre-adolescent to adult population in dengue endemic countries: “The older age groups – of nine years old and above – represent a significant segment of the population experiencing the bulk of dengue cases. The candidate dengue vaccine is expected to provide a positive public health impact on dengue disease burden in these individuals in dengue-endemic areas – contributing to WHO objectives to decrease dengue-related mortality by more than 50% and morbidity by more than 25% by 2020.”

Vaccination, image courtesy, Sri Rezeki Hadinegoro

Ongoing surveillance

The results amongst the younger trial participants were not so spectacular. Efficacy among children younger than nine years was much lower at 44.6%, with 44.5% protection against severe dengue, and 56.1% of dengue hospitalizations prevented. Prof Hadinegoro notes: “Additional surveillance data is needed to provide more information on the overall impact of the vaccination in children in this younger age group.”

Physical examination before vaccination, image courtesy of Prof Sri Rezeki Hadinegoro

She also highlighted that it was important to continue the long-term safety follow-up of the vaccines in the most recent phase three trials.
Another important role played by surveillance – this time during the trials – was in highlighting the under-reporting of dengue cases. Active surveillance during the clinical trials allowed the study teams to confirm the magnitude of under reporting of dengue cases in each participating country. “This highlights the importance of having a good surveillance system in place in each country,” adds Prof Hadinegoro.

The long road ahead

Once the vaccine becomes available, each country must embark on a journey of potentially several years before reaping the benefits of the vaccine. Prof Hadinegoro notes that the most important step will be approval of the vaccine by the National Regulatory Authority in that country. She comments: “Only after the vaccine has been registered and licensed can it go to the market.”
Regulations will be needed before the vaccine can be introduced into national immunization programs. “These regulations will depend on the plan from the Ministry of Health, Ministry of Finance, and Parliament,” reveals Prof Hadinegoro. The first market to use the vaccine once it becomes available will be the private sector, she believes. Unfortunately, it only covers around 10% of the target population. Prof Hadinegoro concludes our discussion by expressing her hopes that the Indonesian government will accept this dengue vaccine and introduce it into a national program faster than other vaccines to help achieve the goal of reducing mortality and morbidity by 2020.
Do you think the dengue vaccine will allow us to win the fight against the growing burden of dengue? Share your thoughts with us!

About Prof Sri Rezeki Hadinegoro:
Prof Sri Rezeki Hadinegoro has been a paediatrician and senior lecturer at Department of Child Health, Division of Infection and Tropical Pediatrics, Faculty of Medicine, University of Indonesia, Dr Cipto Mangunkusumo hospital in Jakarta since 1983. She has since taken an active role in dengue control at the hospital, and the Indonesian Ministry of Health. She has been actively managing the Immunization Task Force at the Indonesian Pediatric Society for 15 years, supporting the government’s national immunization program. The Ministry of Health promoted her to chairman of the Indonesian Technical Advisory Group on Immunization (ITAGI).
In 1996 Prof Hadinegoro earned a PhD from the University of Indonesia, studying “The role of endotoxin in Dengue Hemorrhagic Fever, with focus on cytokine activation”. The university promoted her to professor in 2000. Today she is chairman of the Pediatric Research Center at the Department of Child Health in the university’s hospital. She also gives lectures at many hospitals around Indonesia and has written books for doctors on diagnosing dengue.