Single dengue vaccine dose shows mixed results: Protection hinges on prior exposure

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In a caller study published successful nan diary The Lancet Infectious Diseases, researchers conducted a prospective, longitudinal, population-based cohort study successful 2 communities successful nan Philippines to analyse nan effects of nan prematurely discontinued CYD-TDV vaccine connected children's susceptibility to nan dengue microorganism (DENV). While nan first of 3 required doses of nan vaccine was publically administered successful 2016 by nan Philippine Department of Health, shape 3 CYD-TDV outcomes resulted successful nan vaccination programme being discontinued.

The coming study reveals that nan azygous administered dose of CYD-TDV was incapable of conferring protection against virologically confirmed dengue among patients without a anterior history of DENV infection (zero aliases 1 anterior infection). In stark contrast, young patients who had been exposed to 2 aliases much anterior DENV infections were recovered to person substantially reduced DENV infection consequence pursuing nan first CYD-TDV vaccine dose. This protection was recovered to beryllium long-lasting, pinch nan observed consequence simplification persisting passim nan first 3 years and nan consequent follow-up period.

 frank60 / ShutterstockStudy: Effect of single-dose, live, attenuated dengue vaccine successful children pinch aliases without erstwhile dengue connected consequence of subsequent, virologically confirmed dengue successful Cebu, nan Philippines: a longitudinal, prospective, population-based cohort study. Image Credit: frank60 / Shutterstock

The dengue microorganism and nan request for this study

Dengue (DENV) is simply a mosquito-borne viral illness prevalent worldwide successful tropical and subtropical regions, peculiarly successful agrarian and underdeveloped communities. It tin beryllium caused by immoderate of 4 intimately related viruses (serotypes), fixed that repetition infections are amazingly common. Disease severity tin scope from asymptomatic aliases mild to life-threatening, pinch communal symptoms including precocious fever, persistent headaches, rashes, and characteristic musculus and associated pain.

Despite years of research, dengue remains without a circumstantial cure, pinch objective interventions involving guidance of nan fever and diligent discomfort and pharmacotherapy restricted to communal anti-viral drugs. Thankfully, galore dengue vaccines person been developed and proven effective against nan disease, redeeming countless lives, particularly successful caller decades. One of these vaccines developed successful France successful 2015 was nan CYD-TDV vaccine, targeted astatine children and adolescents.

"In 2015, a three-dose dengue vaccine (CYD-TDV, Dengvaxia, Sanofi Pasteur, Lyon, France) was licensed successful respective dengue-endemic countries successful group aged 9 years and older."

In 2016, nan Philippine Department of Health undertook a vaccination thrust for children successful Calabarzon, Central Luzon, and Metro Manilla utilizing CYD-TDV. Unfortunately, this thrust was recovered to beryllium premature – consequent objective tests revealed that DENV underperformed successful younger children compared to their older counterparts (DENV seropositivity decreases pinch age). More importantly, nan vaccine was recovered to beryllium contraindicated successful patients without a history of DENV infection. These outcomes resulted successful nan vaccination program's termination pursuing nan management of only nan first CYD-TDV vaccine dose.

Hitherto, however, nan effect of that azygous vaccine dose connected children's illness guidance remains unexplored.

About nan study

The coming study aimed to measure nan comparative DENV infection consequence among Cebu children who did aliases did not person a azygous CYD-TVD dose, and nan relation of these outcomes pinch nan number of erstwhile DENV infections survived by these children. The study was designed arsenic a prospective, longitudinal, population-based cohort study and comprised patient children betwixt nan ages of 9 and 14 years from Balamban municipality aliases Bogo city. The study protocol follows nan Strengthening nan Reporting of Observational Studies successful Epidemiology (STROBE) guidelines, pinch information postulation carried retired via a custom-designed questionnaire (demographic information collection) and 5 mL venous humor sample (for baseline DENV serostatus evaluation).

Anthropometric and sociodemographic region information were additionally acquired from nan Rural Health Units, which revealed that retired of 285,242 eligible children, 149,023 had received nan first CYYD-TVD dose. Enrolled participants were assigned to vaccine aliases no-vaccine cohorts based connected these information sources, pinch follow-up humor and questionnaire collections 17-28 months pursuing study initiation.

"A subordinate pinch virologically confirmed dengue was defined arsenic having acute febrile unwellness pinch a affirmative consequence by RT-PCR. We interviewed participants aliases nan genitor aliases guardian successful infirmary aliases astatine location successful personification aliases via telephone to found nan result of nan illness. We classified cases of virologically confirmed dengue according to WHO criteria."

The study's result of liking was nan comparative protection confirmed by nan azygous vaccine dose, measured successful position of nan number of consequent infections pursuing vaccination. Inter-cohort comparisons were statistically achieved utilizing two-sample t tests (mean comparisons) and Wilcoxon rank-sum tests (median comparisons).

Study findings

Of nan 3,087 children who volunteered for nan study, 3,001 were recovered to meet nan study inclusion criteria and were enrolled successful nan study. Of these, 2,778 provided completed demographic and aesculapian information astatine some baseline and follow-up evaluations and were included successful nan last analyses.

Serum sample assays revealed that 241 individuals (10.1%) were DENV naïve, of which 93 were unvaccinated. An overwhelming 1,906 participants (80.3%) were recovered to beryllium DENV multitypic, indicating aggregate infection cycles, perchance by different DENV serotypes.

Analyses of consequent DENV infection information item that nan CYD-TDV dose was insufficient to protect naïve and monotypic floor plan patients from DENV infections, pinch nary statistically discernible quality betwixt individuals who had received nan vaccine and those who had not. In contrast, patients pinch multitype DENV profiles who were past administered nan vaccine dose displayed substantial, long-lasting improvements successful their infection resistance. These results are surprising, arsenic until recently, DENV monotypic patients were assumed to beryllium astatine nan highest infection consequence owed to nan passive immunity of multitypic floor plan patients.

"In summary, we recovered nary protection from a azygous dose of CYD-TDV among children pinch a naive aliases monotypic DENV immune floor plan astatine baseline. One dose conferred important protection against hospitalization for virologically confirmed dengue among children pinch a monotypic DENV immune floor plan astatine baseline. Since only 1 dose of CYD-TDV was given, nan study cannot beryllium utilized to pass nationalist wellness decisions connected vaccination but is applicable for children who person an incomplete regimen."

Journal reference:

  • Ylade, M., Crisostomo, M. V., Daag, J. V., Agrupis, K. A., Cuachin, A. M., Sy, A. K., Kim, D. R., Ahn, H. S., Escoto, A. C., Katzelnick, L. C., Adams, C., White, L., de Silva, A. M., Deen, J., & Lopez, A. L. (2024). Effect of single-dose, live, attenuated dengue vaccine successful children pinch aliases without erstwhile dengue connected consequence of subsequent, virologically confirmed dengue successful Cebu, nan Philippines: a longitudinal, prospective, population-based cohort study. In The Lancet Infectious Diseases. Elsevier BV, DOI – 10.1016/s1473-3099(24)00099-9, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00099-9/fulltext