Vaccines for dengue patients soon - Director General Health Services | Sunday Observer

Vaccines for dengue patients soon - Director General Health Services

Promising results from trials on vaccines to fight dengue, are likely to see the introduction of the long awaited dengue vaccine, and hopefully mitigate morbidity and mortality from the disease that until last month had the country in its grip.

“We looked at three vaccines from France, USA and Japan. Regarding the French vaccine, certain issues have to be resolved. The other two have so far had promising results. The US vaccine has been produced in an Indian manufacturing plant . They have requested Sri Lanka to be included in the phase 3 trial. These two have been found to be definitely effective and suitable for young children and other vulnerable patients,” Director General Health Services ( DGHS) Dr Jayasundera Bandara told the Sunday Observer , Wednesday.

Asked when it was likely the vaccine would be released to the public health program, he said ,,” Perhaps by next year. As I said, the trials carried out using these vaccines from the USA and Japan, have now reached phase 2. We are expecting to do phase 3 which is the final stage. In fact, Sri lanka is already in phase 3 for the Japanese vaccine and expected to be included in the phase 3 trial of the Us vaccine. Thereafter, it is left to the National Medicinal Regulatory Authority ( NMRA) to register them.”

Registering the vaccines however, is not likely to be done overnight, even after approval from the scholarly panel of experts currently checking the vaccine for possible flaws.

As Dr Jayasundara points out, “ Before registration, there are many issues that have to be sorted. In addition, doctors using the vaccine need to be one hundred percent certain that the vaccine is absolutely safe and effective, with no side effects. If not, it could have adverse effects on our vaccination program”.

What were the chances of moving on to registering the drugs and releasing them to the public health program? Could he predict a date in the near future?

“It is unlikely that the registration of the vaccine will happen for some time. You must remember we are dealing with vulnerable people like sick children and pregnant mothers etc. who are at risk when stricken by the more severe form of dengue. Then, there is the problem of costs, which has also to be considered”.

Canour developing nation bear the cost alone? , we asked.

“The Committee will have to decide who is to get the vaccine and in what order. But, one thing I can be sure. We will be putting the vaccine out according to the recommendations of the World Health Organization (W.H.O)”, he said.

WHO’s role in the dengue vaccine development

With its goal of reducing the dengue burden by 2020 looming perilously close, what we wondered was the current role the WHO played in the development of the dengue vaccine.Take a look at its report of April 2016 which answers some questions uppermost in our minds :

“There is a growing public health need for effective preventive interventions against dengue, a disease caused by four viruses, termed serotypes 1-4. A safe, effective and affordable dengue vaccine against the four strains would represent a major advance for the control of the disease and could be an important tool for reaching the WHO goal of reducing dengue morbidity by at least 25% and mortality by at least 50% by 2020. One dengue vaccine has been licensed, Dengvaxia® (CYD-TDV), developed by Sanofi Pasteur. Approximately, five additional dengue vaccine candidates are in clinical development, with two candidates (developed by Butantan and Takeda) expected to begin Phase III trials in early 2016.

CYD-TDV is the first dengue vaccine to be licensed. It was first licensed in Mexico in December 2015 for use in individuals 9-45 years of age living in endemic areas. CYD-TDV is a live recombinant tetravalent dengue vaccine developed by Sanofi Pasteur (CYD-TDV), given as a 3-dose series on a 0/6/12month schedule.

What are the results from the Phase 3 trials?

CYD-TDV has been evaluated in two Phase 3 clinical trials (CYD14 in five countries in Asia and CYD15 in five countries in Latin America). Together, these trials included over 35,000 participants aged 2 to 16 years: ages at first vaccination were 2 to 14 years in CYD14, 9 to 16 years in CYD15. In each of these trials, participants were randomized to vaccine and placebo in a 2:1 ratio. The study protocols included an active phase of follow-up for one year after the last dose of vaccine in the series (25 months from dose 1) and include a hospital-based follow-up period of four additional years, which is ongoing.

Results have been published for each trial separately, as well as pooled. Trial results include children aged below 9, which is an age group that is not included in the current indication. This is due to results that were observed during the Phase 3 trials in the youngest age group in the CYD14 Phase 3 trial.

Vaccine efficacy against confirmed dengue pooled across both trials was 59.2% in the year following the primary series (per protocol analysis). During this initial time period, pooled vaccine efficacy against severe dengue was 79.1%. Efficacy varied by serotype: vaccine efficacy was higher against serotypes 3 and 4 (71.6% and 76.9%, respectively) than for serotypes 1 and 2 (54.7% and 43.0%). Vaccine efficacy also varied by age at vaccination and serostatus at baseline (i.e., previous exposure to dengue prior to vaccination).

When limited to older age groups (ages included in the current licensure), pooled vaccine efficacy among all participants aged 9 or over was 65.6%, and in participants aged below 9 it was 44%.

What are WHO’s recommendations related to CYD-TDV?

WHO recommends that countries should consider introduction of the dengue vaccine CYD-TDV only in geographic settings (national or subnational) where epidemiological data indicate a high burden of disease. Complete recommendations may be found in the WHO position paper on dengue vaccines.

Views of the Epidemiology Unit

What has the Epidemiology Unit of the Health Ministry to say regarding the vaccine?

On the applicability of the dengue vaccine the Weekly Epidemiology Report Vol 4 of March 18-24, 2017, states, “ At present one dengue vaccine , a live attenuated recombinant tetravalent vaccine has been registered in several countries while several other candidates are in clinical development. There are 2 other candidates currently under evaluation in Phase III trials which are also tetravalent live attenuated (recombinant) vaccines.

Based on data collected from Phase II studies, the majority of sero-positive subjects have a tetravalent response after two doses. In sero-negative subjects, the proportion with a tetravalent response is lower than in the sero-positive subjects. The 3-dose series increased the proportion of subjects with a tetravalent response as compared to the 2-dose series, although many sero-negative subjects still did not have a tetravalent response after 3 doses. However, sero-conversion alone does not predict protection. Additional investigations are ongoing to further characterize the relationship between immunologic markers and protection against disease.

Vaccine efficacy was higher in individuals who were sero-positive at baseline compared to those who were sero-negative at baseline. Age and sero-positivity were highly correlated in the trials. Efficacy varied from country to country in the studies, ranging from 31.3% (95% CI 1.3%–51.9%) in Mexico to 79.0% (95% CI 52.3%–91.5%) in Malaysia. This variability in efficacy likely reflects, at least in part, the baseline sero-positivity and circulating serotypes, both of which affect the performance of the vaccine.

During the vaccine studies, an increased risk of hospitalized dengue was identified in one age group (2–5 years) which was unlikely to be due to chance. Several hypotheses suggested to explain this, including that in sero-negative children, of whom there is a higher percentage in the youngest age groups, the vaccine may act as a silent natural infection that primes sero-negative vaccines to experience a secondary-like infection upon their first exposure to dengue virus. Therefore, it was decided to start the indicated age range for vaccination at 9 years. Vaccination may be ineffective or may theoretically even increase the future risk of dengue illness in those who are sero-negative at the time of first vaccination regardless of age. If this is the case, even in high transmission settings there may be increased risk among sero-negative persons despite a reduction in dengue illness at the population level. Mathematical models have been developed to predict the dosage.”

Current dengue situation

Asked to comment on the current dengue situation in the country and his prediction for the future, Dr Jayasundara said, the latest epidemiology figures had shown a drastic reduction in the number of suspected cases across the country. ‘ June was the peak month when it reached a record high . But, thanks to the hard work and support of all , we have been able to bring down the figures by more than we expected. When we started our Dengue Prevention programs we expected to see a fifty percent reduction. But now there is an 80% reduction . However, we cannot afford to be complacent since the next monsoon is expected in October. We need to minimize the breeding sites of the dengue carrying vector by keeping our neighbourhoods and gardens clean. If not, there could be another epidemic”. he warned..

Community based study

Conflicting estimates of the disease burden of dengue have often left health authorities battling the disease, confused. Now, the Epidemiology Unit of the Health Ministry has stepped in to remove that gap.

Unit sources said, in order to understand the prevalence of dengue in the country, especially, in high risk areas like the Western Province, a Community based descriptive study of dengue sero epidemiology had been initiated in the Colombo district. “Age specific and rural population in the Colombo district will be assessed in the study “, a spokesman said. “The outcome will be useful to obtain more accurate estimates of the disease burden both, serologically and epidemiologically . Another component of the study will also look at the burden of the disease through disability. Adjusted Life Years of DALYS will be attempted for the first time in Sri Lanka”.

Current dengue cases islandwide

During the last 9 months of year 2017, 151,330 suspected dengue cases have been reported to the Epidemiology Unit from all over the island.

Approximately, 43.55% of dengue cases were reported from the Western Province. The highest numbers of dengue cases were reported during the 29 week of 2017.

In this respect, Epidemiology Chief Dr S.Ginige has this advice to offer the public: “ Regularly remove possible mosquito breeding sites from the environment. Seek medical attention in the event of fever by day three of the illness. Refrain from taking any medication other than paracetamol as advised by the doctor”. 

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