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Fulltext Potential impact of dengue vaccination: Insights from two large-scale phase III trials with a tetravalent dengue vaccine

Coudeville L, Baurin N, L'Azou M, Guy B

Vaccine, 2016 12 07;34(50):6426-6435.
PMID: 27601343 DOI: 10.1016/j.vaccine.2016.08.050

BACKGROUND: A tetravalent dengue vaccine demonstrated its protective efficacy in two phase III efficacy studies. Results from these studies were used to derive vaccination impact in the five Asian (Indonesia, Malaysia, Philippines, Thailand, Vietnam) and the five Latin American countries (Brazil, Colombia, Honduras, Mexico and Puerto Rico) participating in these trials.
METHODS: Vaccination impact was investigated with an age-structured, host-vector, serotype-specific compartmental model. Parameters related to vaccine efficacy and levels of dengue transmission were estimated using data collected during the phase III efficacy studies. Several vaccination programs, including routine vaccination at different ages with and without large catch-up campaigns, were investigated.
RESULTS: All vaccination programs explored translated into significant reductions in dengue cases at the population level over the first 10years following vaccine introduction and beyond. The most efficient age for vaccination varied according to transmission intensity and 9years was close to the most efficient age across all settings. The combination of routine vaccination and large catch-up campaigns was found to enable a rapid reduction of dengue burden after vaccine introduction.
CONCLUSION: Our analysis suggests that dengue vaccination can significantly reduce the public health impact of dengue in countries where the disease is endemic.
Fulltext Epidemiology of dengue disease in Malaysia (2000-2012): a systematic literature review

Mohd-Zaki AH, Brett J, Ismail E, L'Azou M

PLoS Negl Trop Dis, 2014;8(11):e3159.
PMID: 25375211 DOI: 10.1371/journal.pntd.0003159

A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Malaysia between 2000 and 2012. Published literature was searched for epidemiological studies of dengue disease, using specific search strategies for each electronic database; 237 relevant data sources were identified, 28 of which fulfilled the inclusion criteria. The epidemiology of dengue disease in Malaysia was characterized by a non-linear increase in the number of reported cases from 7,103 in 2000 to 46,171 in 2010, and a shift in the age range predominance from children toward adults. The overall increase in dengue disease was accompanied by a rise in the number, but not the proportion, of severe cases. The dominant circulating dengue virus serotypes changed continually over the decade and differed between states. Several gaps in epidemiological knowledge were identified; in particular, studies of regional differences, age-stratified seroprevalence, and hospital admissions.
PROTOCOL REGISTRATION: PROSPERO #CRD42012002293.
Fulltext Symptomatic dengue in children in 10 Asian and Latin American countries

L'Azou M, Moureau A, Sarti E, Nealon J, Zambrano B, Wartel TA, et al.

N Engl J Med, 2016 Mar 24;374(12):1155-66.
PMID: 27007959 DOI: 10.1056/NEJMoa1503877

BACKGROUND: The control groups in two phase 3 trials of dengue vaccine efficacy included two large regional cohorts that were followed up for dengue infection. These cohorts provided a sample for epidemiologic analyses of symptomatic dengue in children across 10 countries in Southeast Asia and Latin America in which dengue is endemic.
METHODS: We monitored acute febrile illness and virologically confirmed dengue (VCD) in 3424 healthy children, 2 to 16 years of age, in Asia (Indonesia, Malaysia, the Philippines, Thailand, and Vietnam) from June 2011 through December 2013 and in 6939 children, 9 to 18 years of age, in Latin America (Brazil, Colombia, Honduras, Mexico, and Puerto Rico) from June 2011 through April 2014. Acute febrile episodes were determined to be VCD by means of a nonstructural protein 1 antigen immunoassay and reverse-transcriptase-polymerase-chain-reaction assays. Dengue hemorrhagic fever was defined according to 1997 World Health Organization criteria.
RESULTS: Approximately 10% of the febrile episodes in each cohort were confirmed to be VCD, with 319 VCD episodes (4.6 episodes per 100 person-years) occurring in the Asian cohort and 389 VCD episodes (2.9 episodes per 100 person-years) occurring in the Latin American cohort; no trend according to age group was observed. The incidence of dengue hemorrhagic fever was less than 0.3 episodes per 100 person-years in each cohort. The percentage of VCD episodes requiring hospitalization was 19.1% in the Asian cohort and 11.1% in the Latin American cohort. In comparable age groups (9 to 12 years and 13 to 16 years), the burden of dengue was higher in Asia than in Latin America.
CONCLUSIONS: The burdens of dengue were substantial in the two regions and in all age groups. Burdens varied widely according to country, but the rates were generally higher and the disease more frequently severe in Asian countries than in Latin American countries. (Funded by Sanofi Pasteur; CYD14 and CYD15 ClinicalTrials.gov numbers, NCT01373281 and NCT01374516.).
Note: Malaysia is a study site (CYD14 Primary Study Group authors: HIHJMI, Pediatric Institute, Kuala Lumpur Hospital, Kuala Lumpur; RN, Department of Paediatrics, Hospital Pulau Pinang, Pulau Pinang, Malaysia)
Fulltext Symptomatic Dengue Disease in Five Southeast Asian Countries: Epidemiological Evidence from a Dengue Vaccine Trial

Nealon J, Taurel AF, Capeding MR, Tran NH, Hadinegoro SR, Chotpitayasunondh T, et al.

PLoS Negl Trop Dis, 2016 Aug;10(8):e0004918.
PMID: 27532617 DOI: 10.1371/journal.pntd.0004918

Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2-14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14's active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions.