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Background: The Brazilian state of Parana conducted a mass vaccination campaign against dengue with the tetravalent attenuated vaccine CYD-TDV. The campaign targeted thirty endemic municipalities. The objective of this study was to assess the effectiveness of CYD-TDV in preventing symptomatic virologically confirmed dengue cases according to specific age groups in five of the municipalities. Methods: A case-control study was carried out in the five most populous municipalities targeted by the vaccination, with a vaccine uptake of 25%. Symptomatic dengue cases were identified by the municipal health departments. The age groups targeted were 15–18 and 19–27 in four municipalities and 9–14 and 28–44 in one municipality. All cases were confirmed by real time reverse transcription quantitative polymerase chain reaction (RT-qPCR). For each case, two controls were selected: a neighborhood control and a workplace or school/college control, matched by age group. A conditional logistic regression model was used to determine the odds ratio for vaccination and the vaccine effectiveness. Findings: Study participants included 618 RT-qPCR-confirmed dengue cases and 1,236 matched controls (with a non-reactive dengue IgM serologic test). Vaccine effectiveness against dengue due to any serotype was 11·1% (95% CI: –19·0%; 33·6%). Effectiveness against DENV-1 was 33·3% (95% CI: -5·0%; 57·6%) and against DENV-2 was -56·7% (95% CI: -142·2%; -5·0%). No DENV-3 were detected. The vaccine was significantly effective in the prevention of DENV-4 cases (VE = 93·3%; 95% CI: 47·7%; 99·2%). Interpretation: CYD-TDV was effective in the prevention of symptomatic cases due to DENV-4, but not due to any serotype. The low dengue sero-prevalence in the target population could possibly be related to these results. Funding: This study was supported through a grant to the Sabin Vaccine Institute from Sanofi-Pasteur. Sanofi-Pasteur had no role in the study design, protocol development, data collection, analysis, or publication of results. Declaration of Interest: EJA Luna and JC Moraes have received consultancy fees and travel sponsorship from Sanofi-Pasteur. D Garrett, F. Crosewski, I Riediger, F Fantinato and K Ribeiro declare no conflict of interest. Ethical Approval: The Santa Casa de Sao Paulo Research Ethics Committee (Resolution no. 1817892, on November 11, 2016) and Pan American Health Organization Ethics Review Committee – PAHOERC (Resolution PAHO 2016-11-0056) approved the study protocol.

Background: Precise enteric fever disease burden data are needed to inform prevention and control measures, including the use of newly available typhoid vaccines. To inform these strategies, the Surveillance for Enteric Fever in Asia Project (SEAP) conducted prospective, facility-based surveillance for Salmonella Typhi and S . Paratyphi A from 2016-2019. Methods: To generate population-based incidence estimates of enteric fever, we conducted prospective clinical surveillance at five hospitals in pre-determined catchment areas in Dhaka, Bangladesh, Kathmandu and Kavrepalanchok, Nepal, and Karachi, Pakistan. We employed a hybrid surveillance model, pairing facility-based blood culture surveillance with community surveys of healthcare utilization. Blood cultures were performed for enrolled patients. We calculated overall and age-specific typhoid and paratyphoid incidence estimates for each study site. Adjusted estimates accounted for the sensitivity of blood culture, the proportion of eligible individuals who consented and provided blood, the probability of care-seeking at a study facility, and the influence of wealth and education on care-seeking. Findings: Of the 33,136 blood cultures performed on enrolled patients, 8,705 (26%) were positive for typhoidal Salmonella . Adjusted incidence of S . Typhi, expressed per 100,000 person-years, was 1,110 (95% CI: 949-1,305) in Dhaka. In Nepal, the adjusted typhoid incidence rates were 330 (95% CI: 232-476) in Kathmandu and 271 (95% CI:205-365) in Kavrepalanchok. In Pakistan, the adjusted incidence rates per hospital site were 195 (95% CI:163-236) and 126 (95% CI:106-151). Although lower than the rates of typhoid, the adjusted incidence rates of paratyphoid were 150 ( 95% CI: 127-177) in Bangladesh, 49 (95% CI: 38-65) and 82 (95% CI: 57-116) in the Nepal sites, and 25 (95% CI: 21-31) and 1 (95% CI: 1-1) in the Pakistan sites. Adjusted incidence of hospitalization was high across sites, and overall 32% of case patients were hospitalized. Interpretation: Across diverse communities in three South Asian countries, adjusted incidence exceeded the threshold for “high burden” of enteric fever (100 per 100,000 person-years). Incidence was highest among children, although age patterns differed across sites. The substantial disease burden identified highlights the need for control measures, including improvements to water and sanitation infrastructure and the implementation of typhoid vaccines. Funding: This work was supported by a grant from the Bill and Melinda Gates Foundation (grant number INV-008335). Declaration of Interest: None to declare. Ethical Approval: We obtained written informed consent from all eligible participants and the parents/guardians of participants aged