Background Takeda’s dengue vaccine is under evaluation in an ongoing phase 3 efficacy study; we p... more Background Takeda’s dengue vaccine is under evaluation in an ongoing phase 3 efficacy study; we present a 2-year update. Methods Children (20 099, 4–16 years old) were randomized to receive 2 doses of TAK-003 or placebo 3 months apart and are under surveillance to detect dengue by serotype-specific RT-PCR. Results Cumulative efficacy against dengue approximately 27 months since first dose was 72.7% (95% confidence interval [CI], 67.1%–77.3%), including 67.0% (95% CI, 53.6%–76.5%) in dengue-naive and 89.2% (95% CI, 82.4%–93.3%) against hospitalized dengue. In the second year, decline in efficacy was observed (56.2%; 95% CI, 42.3%–66.8%) with the largest decline in 4–5 year olds (24.5%; 95% CI, −34.2% to 57.5%); efficacy was 60.6% (95% CI, 43.8%–72.4%) in 6–11 year and 71.2% (95% CI, 41.0%–85.9%) in 12–16 year age groups. As TAK-003 efficacy varies by serotype, changes in serotype dominance partially contributed to efficacy differences in year-by-year analysis. No related serious adve...
Here, we present the complete genome sequences of two Zika virus (ZIKV) strains, Zika virus/Homo ... more Here, we present the complete genome sequences of two Zika virus (ZIKV) strains, Zika virus/Homo sapiens-tc/THA/2014/SV0127-14 and Zika virus/H. sapiens-tc/PHL/2012/CPC-0740, isolated from the blood of patients collected in Thailand, 2014, and the Philippines, 2012, respectively. Sequencing and phylogenetic analysis showed that both strains belong to the Asian lineage.
Background Takeda’s live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evalu... more Background Takeda’s live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across eight dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year post-vaccination. This exploratory analysis provides an update with cumulative and third year data. Methods Healthy 4–16 year-olds (n=20,099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific RT-PCR. Results Cumulative efficacy after three years was 62.0% (95% confidence interval: 56.6%, 66.7%) against virologically-confirmed dengue (VCD) and 83.6% (76.8%, 88.4%) against hospitalized VCD. Efficacy was 54.3% (41.9%, 64.1%) against VCD and...
To establish a new method for the diagnosis of dengue secondary infection, 187 serum samples from... more To establish a new method for the diagnosis of dengue secondary infection, 187 serum samples from the patients with dengue secondary infection, 40 serum samples from the patients with dengue primary infection, and 44 serum samples from the healthy volunteers were tested using the dengue IgG indirect enzyme-linked immunosorbent assay (DEN IgG ELISA). The results of the test were compared with those from the dengue hemagglutination inhibition (DEN HI) test, which has been recommended as the gold standard by the World Health Organization (WHO, 1997). Japanese encephalitis IgG indirect ELISA (JE IgG ELISA) was also performed to measure anti-flavivirus IgG, which cross-reacts with the Japanese encephalitis virus, to test the possibility of an alternative to DEN IgG ELISA. The results of DEN IgG and JE IgG ELISAs were highly correlated with those of the DEN HI test. In the DEN IgG ELISA, a titer of 1:29,000 was the cut-off value for the diagnosis of dengue secondary infection (91.5% accuracy [95% confidence interval, CI], 90.9% sensitivity [95%CI], and 92.9% specificity [95%CI]). A titer of 1:52,000 was the cut-off value for dengue secondary infection using JE IgG ELISA (95.6% accuracy [95%CI], 98.9% sensitivity [95%CI], and 88.1% specificity [95%CI]). In conclusion, this study confirmed that the results of both DEN IgG and JE IgG ELISAs were highly correlated with the results of DEN HI test. Thus, these ELISAs are simple, rapid, sensitive, and quantitative tests that can be used in the determination of dengue secondary infection.
Background Takeda’s dengue vaccine is under evaluation in an ongoing phase 3 efficacy study; we p... more Background Takeda’s dengue vaccine is under evaluation in an ongoing phase 3 efficacy study; we present a 2-year update. Methods Children (20 099, 4–16 years old) were randomized to receive 2 doses of TAK-003 or placebo 3 months apart and are under surveillance to detect dengue by serotype-specific RT-PCR. Results Cumulative efficacy against dengue approximately 27 months since first dose was 72.7% (95% confidence interval [CI], 67.1%–77.3%), including 67.0% (95% CI, 53.6%–76.5%) in dengue-naive and 89.2% (95% CI, 82.4%–93.3%) against hospitalized dengue. In the second year, decline in efficacy was observed (56.2%; 95% CI, 42.3%–66.8%) with the largest decline in 4–5 year olds (24.5%; 95% CI, −34.2% to 57.5%); efficacy was 60.6% (95% CI, 43.8%–72.4%) in 6–11 year and 71.2% (95% CI, 41.0%–85.9%) in 12–16 year age groups. As TAK-003 efficacy varies by serotype, changes in serotype dominance partially contributed to efficacy differences in year-by-year analysis. No related serious adve...
Here, we present the complete genome sequences of two Zika virus (ZIKV) strains, Zika virus/Homo ... more Here, we present the complete genome sequences of two Zika virus (ZIKV) strains, Zika virus/Homo sapiens-tc/THA/2014/SV0127-14 and Zika virus/H. sapiens-tc/PHL/2012/CPC-0740, isolated from the blood of patients collected in Thailand, 2014, and the Philippines, 2012, respectively. Sequencing and phylogenetic analysis showed that both strains belong to the Asian lineage.
Background Takeda’s live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evalu... more Background Takeda’s live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across eight dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year post-vaccination. This exploratory analysis provides an update with cumulative and third year data. Methods Healthy 4–16 year-olds (n=20,099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific RT-PCR. Results Cumulative efficacy after three years was 62.0% (95% confidence interval: 56.6%, 66.7%) against virologically-confirmed dengue (VCD) and 83.6% (76.8%, 88.4%) against hospitalized VCD. Efficacy was 54.3% (41.9%, 64.1%) against VCD and...
To establish a new method for the diagnosis of dengue secondary infection, 187 serum samples from... more To establish a new method for the diagnosis of dengue secondary infection, 187 serum samples from the patients with dengue secondary infection, 40 serum samples from the patients with dengue primary infection, and 44 serum samples from the healthy volunteers were tested using the dengue IgG indirect enzyme-linked immunosorbent assay (DEN IgG ELISA). The results of the test were compared with those from the dengue hemagglutination inhibition (DEN HI) test, which has been recommended as the gold standard by the World Health Organization (WHO, 1997). Japanese encephalitis IgG indirect ELISA (JE IgG ELISA) was also performed to measure anti-flavivirus IgG, which cross-reacts with the Japanese encephalitis virus, to test the possibility of an alternative to DEN IgG ELISA. The results of DEN IgG and JE IgG ELISAs were highly correlated with those of the DEN HI test. In the DEN IgG ELISA, a titer of 1:29,000 was the cut-off value for the diagnosis of dengue secondary infection (91.5% accuracy [95% confidence interval, CI], 90.9% sensitivity [95%CI], and 92.9% specificity [95%CI]). A titer of 1:52,000 was the cut-off value for dengue secondary infection using JE IgG ELISA (95.6% accuracy [95%CI], 98.9% sensitivity [95%CI], and 88.1% specificity [95%CI]). In conclusion, this study confirmed that the results of both DEN IgG and JE IgG ELISAs were highly correlated with the results of DEN HI test. Thus, these ELISAs are simple, rapid, sensitive, and quantitative tests that can be used in the determination of dengue secondary infection.
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Papers by Maria Theresa Alera