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Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

In the CYD14 trial of the CYD-TDV dengue vaccine in 2-14 year-olds, neutralizing antibody (nAb) titers to the vaccine-insert dengue strains correlated inversely with symptomatic, virologically-confirmed dengue (VCD). Also, vaccine efficacy against VCD was higher against dengue prM/E amino acid sequences closer to the vaccine inserts. We integrated the nAb and sequence data types by assessing nAb titers as a correlate of sequence-specific VCD separately in the vaccine arm and in the placebo arm. In both vaccine and placebo recipients the correlation of nAb titer with sequence-specific VCD was stronger for dengue nAb contact site sequences closer to the vaccine (p = 0.005 and p = 0.012, respectively). The risk of VCD in vaccine (placebo) recipients was 6.7- (1.80)-fold lower at the 90th vs 10th percentile of nAb for viruses perfectly matched to CYD-TDV, compared to 2.1- (0.78)-fold lower at the 90th vs 10th percentile for viruses with five amino acid mismatches. The evidence for a stronger sequence-distance dependent correlate of risk for the vaccine arm indicates departure from the Prentice criteria for a valid sequence-distance specific surrogate endpoint and suggests that the nAb marker may affect dengue risk differently depending on whether nAbs arise from infection or also by vaccination. However, when restricting to baseline-seropositive 9-14 year-olds, the correlation pattern became more similar between the vaccine and placebo arms, supporting nAb titers as an approximate surrogate endpoint in this population. No sequence-specific nAb titer correlates of VCD were seen in baseline-seronegative participants. Integrated immune response/pathogen sequence data correlates analyses could help increase knowledge of correlates of risk and surrogate endpoints for other vaccines against genetically diverse pathogens. Trial registration: EU Clinical Trials Register 2014-001708-24; registration date 2014-05-26., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Objective: Cervical cancer is the second most common malignancy affecting females in Southeast Asia. Human Papillomavirus (HPV) vaccines have been available since 2006. Several Association of Southeast Asian Nations (ASEAN) member countries have since introduced and/or piloted the HPV vaccine with adolescent females. This systematic review was conducted to understand what factors influence parents' acceptance of the HPV vaccine in the region., Methods: Seven databases were searched for qualitative and quantitative studies published up to 16 April 2020. Papers were included if they were peer-reviewed, in English, available in full text, and had a focus on parents' knowledge, beliefs, attitudes and acceptance of the HPV vaccine. Findings were integrated to answer the review question using framework analysis based on the Theory of Planned Behaviour., Results: Sixteen publications were included and synthesised under the Theory of Planned Behaviour domains: 1) Knowledge, attitudes and acceptance, 2) subjective norms, and 3) perceived behavioural control. Parents' attitudes to HPV vaccination were positive and acceptance to vaccinate their daughters against HPV was high. The uptake was high when the vaccine was offered for free., Conclusion: Parents' acceptance and uptake of the HPV vaccine in ASEAN member-countries was high when the vaccine was offered for free even though their knowledge of cervical cancer and HPV was poor. Further research is needed to see how uptake and acceptance can be maintain when the vaccine is not offered for free., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Incomplete childhood vaccination is associated with caregiver vaccine hesitancy, conceptualized by "3 Cs": high complacency, low confidence, and low convenience. To expand on existing evidence drawn primarily from the Americas and Europe, and develop culturally appropriate interventions, this research explored drivers of vaccine hesitancy in the Central Asian country of Tajikistan., Methods: In twelve diverse districts, clinic-based immunization record abstraction identified purposive samples of children who were up-to-date (N = 300) or not (N = 300) on all first year vaccines. Using a modified case-control design, the structured face-to-face in-home survey of 600 caregivers compared knowledge, attitudes and practices regarding childhood vaccination by up-to-date status. Socio-demographic and psychological factors associated with hesitancy were identified, using a 22-item vaccine hesitancy scale, with subscales measuring complacency, confidence, and convenience. Overall contribution of vaccine hesitancy to up-to-date status was modeled, adjusting for other significant covariates., Results: Caregivers of not up-to-date children were more likely to report their child's health as poor, and report many logistical barriers to vaccination. Knowledge of vaccine-preventable illnesses was low, and complacency regarding vaccination was high among not up-to-date caregivers. In final multivariable models of predisposing, enabling and reinforcing influences on vaccination status, urban children, those with transportation and employed mothers were more likely to be up-to-date, while not up-to-date children included those born at home, seen as having fair or poor health, or reportedly told by clinicians to avoid immunization. Reinforcing factors included having a "vaccine passport", receiving useful information from medical providers, and believing that vaccine-preventable illnesses are serious and that most in their community are vaccinated. Additionally, vaccine hesitancy was negatively associated with up-to-date status (odds ratio 0.15, 95% C.I. 0.08, 0.26)., Conclusions: Results confirm that in this traditional culture, there is a strong need for tailored communication campaigns to address vaccine hesitancy, while continuing to address systems-level barriers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Influenza is a disease responsible for thousands of deaths every year. Although healthcare workers (HCWs) represent a way of contagion for patients, vaccination coverage among them is low. Mandatory vaccination has been proposed, but controversies remain. This systematic review and meta-analysis aimed to assess the acceptance of mandatory vaccination by HCWs, and to investigate associated characteristics. MEDLINE, Scopus, Embase, PsycInfo, CINAHL and Web of Science were used to search for studies assessing the topic. PRISMA statements were followed. Of the 13,457 univocal records found, 52 studies were included in the systematic review and 40 in the meta-analysis. The pooled proportion of HCWs accepting the policy was of 61% (95% CI: 53%- 68%) but with great heterogeneity between continents (from 54% in Europe to 69% in Asia) and in different professionals (from 40% in nurses to 80% in students). Vaccinated HCWs agreed more frequently with mandatory vaccination than non-vaccinated ones. More studies that consider mandatory vaccination acceptance as the main outcome are needed, but the results of this study confirm that in some settings the majority of HCWs favour mandatory vaccination. This, combined with effects that a flu epidemic could have if overlapped to pandemics with similar symptoms, requires renewed considerations on mandatory vaccination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A vaccine for COVID-19 is urgently needed. Several vaccine trial designs may significantly accelerate vaccine testing and approval, but also increase risks to human subjects. Concerns about whether the public would see such designs as ethical represent an important roadblock to their implementation; accordingly, both the World Health Organization and numerous scholars have called for consulting the public regarding them. We answered these calls by conducting a cross-national survey (n = 5920) in Australia, Canada, Hong Kong, New Zealand, South Africa, Singapore, the United Kingdom, and the United States. The survey explained key differences between traditional vaccine trials and two accelerated designs: a challenge trial or a trial integrating a Phase II safety and immunogenicity trial into a larger Phase III efficacy trial. Respondents' answers to comprehension questions indicate that they largely understood the key differences and ethical trade-offs between the designs from our descriptions. We asked respondents whether they would prefer scientists to conduct traditional trials or one of these two accelerated designs. We found broad majorities prefer for scientists to conduct challenge trials (75%) and integrated trials (63%) over standard trials. Even as respondents acknowledged the risks, they perceived both accelerated trials as similarly ethical to standard trial designs. This high support is consistent across every geography and demographic subgroup we examined, including vulnerable populations. These findings may help assuage some of the concerns surrounding accelerated designs., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The heat-stable live-attenuated classical swine fever virus (CSFV) vaccine is an urgent need in many countries of Asia, Europe and Latin America. In this study, the thermostability of lyophilized live-attenuated CSFV vaccine formulations were investigated using accelerated stability at 37 °C for 10 days. The freeze-dried heat-stable formulation ST16, containing excipient combinations of trehalose, glycine, thiourea and phosphate buffer shows the superior thermostability. Moreover, the lyophilized vaccine with formula ST16 kept loss of viral activity less than 0.5 log 10 during 24 months at storage temperatures of 2-8 °C. In thermal study, ST16 stabilized the vaccine within 1.0 log 10 loss after storage at up to 25 °C for 6 months and room temperature for 7 months. Even under the harshest storage conditions of 37 °C for 25 days and 45 °C for 2 weeks, the virus titer dropped less than 1.0 log 10 using ST16. Besides, it is notable that ST16 excluded gelatin and exogenous proteins, which might cause allergic reactions, thus avoiding immune side effects. The vaccine formulated ST16 proved to be safe and effective when immunized to piglets in vivo. The characteristics of dried vaccines were analyzed by X-ray powder diffraction, residual water measurements, differential scanning calorimetry and it was found that vaccine antigen were preserved in an amorphous matrix with high glass transition temperature above 60 °C and low residual water content below 2%, which made the vaccine more stable during storage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Development of multivalent hand, foot, and mouth disease (HFMD) vaccines against enterovirus A71 (EV-A71) and several non-EV-A71 enteroviruses is needed for this life-threatening disease with a huge economic burden in Asia-Pacific countries. Comprehensive studies on the molecular epidemiology and genetic and antigenic characterization of major causative enteroviruses will provide information for rational vaccine design. Compared with molecular studies on EV-A71, that for non-EV-A71 enteroviruses remain few and limited in Vietnam. Therefore, we conducted a 10-year study on the circulation and genetic characterization of coxsackievirus A16 (CV-A16) and CV-A6 isolated from patients with HFMD in Northern Vietnam between 2008 and 2017. Enteroviruses were detected in 2228 of 3212 enrolled patients. Of the 42 serotypes assigned, 28.4% and 22.4% accounted for CV-A6 and CV-A16, being the second and the third dominant serotypes after EV-A71 (31.7%), respectively. The circulation of CV-A16 and CV-A6 showed a wide geographic distribution and distinct periodicity. Phylogenetic analyses revealed that the majority of Vietnamese CV-A6 and CV-A16 strains were located within the largest sub-genotypes or sub-genogroups. These comprised strains isolated from patients with HFMD worldwide during the past decade and the Vietnamese strains have been evolving in a manner similar to the strains circulating worldwide. Amino acid sequences of the putative functional loops on VP1 and other VPs among Vietnamese CV-A6 and CV-A16 isolates were highly conserved. Moreover, the functional loop patterns of VP1 were similar to the dominant patterns found worldwide, except for the T164K substitution on the EF loop in Vietnamese CV-A16. The findings suggest that the development of a universal HFMD vaccine, at least in Vietnam, must target CV-A6 and CV-A16 as two of the three major HFMD-causing serotypes. Vietnamese isolates or their genome sequences can be considered for rational vaccine design., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Japanese encephalitis (JE) virus is an important cause of neurological disease in Asia. JE vaccine is recommended for travelers with higher JE risk itineraries. Inactivated Vero cell culture-derived JE vaccine (JE-VC) is the only JE vaccine currently available in the United States. An inactivated mouse brain-derived JE vaccine (JE-MB) previously was available but production was discontinued. One JE-VC dose administered to adults previously vaccinated with ≥3 doses of JE-MB provides good short-term protection for at least one month, but data on longer-term protection are limited. We evaluated non-inferiority of the JE virus neutralizing antibody response at 12-23 months in JE-MB-vaccinated adults administered one JE-VC dose compared with JE vaccine-naïve adults administered a JE-VC two-dose primary series., Methods: We obtained archived sera from U.S. military personnel and performed a 50% plaque reduction neutralization test for anti-JE virus neutralizing antibodies. We compared the geometric mean titer (GMT) and seroprotection rate at 12-23 months after one JE-VC dose in previously JE-MB-vaccinated personnel and after the second JE-VC dose in previously JE vaccine-naïve personnel. Non-inferiority was concluded if the lower bound of the two-sided 95% confidence interval (CI) of the GMT ratio in previously vaccinated to vaccine-naïve personnel was >1/1.5., Results: The GMT in previously JE-MB-vaccinated persons was 75 (95% CI 63-90) and in previously JE vaccine-naïve persons was 12 (95% CI 11-14), and seroprotection rates were 94% (235/250) and 54% (135/250), respectively. The ratio of GMTs was 6.3 (95% CI: 5.0-7.7), satisfying the criterion for non-inferiority., Conclusions: One JE-VC dose in previously JE-MB-vaccinated military personnel provides good protection for at least 1-2 years. The benefits of administration of a single JE-VC dose in previously JE-MB-vaccinated adults include a shorter time to completion of re-vaccination before travel, a decrease in the risk of adverse events, and reduced costs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Background: Two rotavirus vaccines (RV1 and RV5) are available on the private market in Taiwan, not included in national immunization program. Scanty reports evaluated the rotavirus vaccine effectiveness (VE) in Asian countries., Methods: From February 2014-July 2017, we conducted a prospective case-control study in ten hospitals in Taiwan. Case-patients included children aged 8-59 months, and hospitalized with laboratory-confirmed rotavirus acute gastroenteritis (AGE). For each case patient, up to four controls, rotavirus-negative AGE or non-AGE illnesses, respectively, were matched by gender, age and enrolled date. Vaccination history was confirmed through vaccination card or hospital record. VE was calculated as (1 - odds ratio of vaccination) × 100%., Results: Totally 4248 AGE patients and 2242 non-AGE controls were enrolled. A total of 330 case-patients with rotavirus AGE, 1226 rotavirus-negative AGE controls and 1122 non-AGE controls were included for analysis. Unvaccinated rate was 85.15% for rotavirus-positive cases, 42.9% for rotavirus-negative controls, and 34.31% for non-AGE controls. VE of two-dose RV1 was 84.9% (95% confidence interval [CI]:77.7%, 90.1%) for rotavirus-negative AGE and 88.9% (95% CI: 83.4%, 92.8%) for non-AGE controls, while VE of three-dose RV5 was 92.5% (95% CI: 85.1%, 96.7%) and 96.4% (95% CI: 91.9%, 98.6%), respectively. For respective vaccine, VEs were not significantly different in term of rotavirus genotypes. VEs of both vaccines declined <80% in children aged three years by combined controls., Conclusions: Both vaccines provided excellent and sustained protection against rotavirus AGE hospitalization in children in Taiwan, but the effectiveness declined slightly in children aged three years., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Reducing the number of doses required for pre-exposure prophylaxis (PrEP) would make it more feasible and cost-effective to implement in children at the highest risk of rabies exposure in Asia. We studied immune response of 2-site intradermal (ID) injection of rabies vaccine on days 0 and 28 for rabies PrEP simultaneously administrated with live-attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) for children living in endemic area., Research Design and Methods: Seronegative children (n = 49) aged 12-16 months were randomized 2:1 into two groups: Group A subjects were vaccinated with 0.1-mL ID injection of purified Vero cell rabies vaccine (PVRV), each at two sites on day (D) 0 and D28; Group B subjects were vaccinated with conventional 0.5-mL intramuscular PVRV on D0, D7 and D28. Both groups received one dose of JE-CV subcutaneously on D0 and D365. Rabies virus neutralizing antibody (RVNA) titers were measured on D0, D42 and D365 after vaccination; Japanese Encephalitis (JE) neutralizing antibody titers were determined on D0, D42, D365 and D379., Results: All children had RVNA ≥ 0.5 IU/mL on D42 (geometric mean titers [GMTs] of RVNA 14.35 IU/mL [Group A] and 14.83 IU/mL [Group B], p > 0.05]). On D365, RVNA GMTs of subjects in group A and B were 1.50 IU/mL and 2.00 IU/mL (p > 0.05), respectively. All children had seroprotection following booster dose of JE-CV. There were no vaccine-related SAEs observed., Conclusion: The 2-site ID PrEP with PVRV on days 0 and 28 co-administrated with JE-CV are safe and immunogenic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Typhoid fever remains an important public health problem in developing countries and is endemic in many parts of Asia and Africa where the incidence of disease typically peaks in school-aged children. Age restrictions and other limitations of existing oral live-attenuated typhoid and parenteral Vi polysaccharide vaccines have triggered the development of Vi conjugate vaccines with improved immunological properties, use in younger age range, and longer durability of protection. We present the safety, reactogenicity, and immunogenicity data from a Phase II study after a single dose of Vi polysaccharide conjugated to diphtheria toxoid (Vi-DT) conducted in 6-23-month old Filipino children., Methods: This is a randomized, observer-blinded Phase II study to assess the immunogenicity, safety and reactogenicity of Vi-DT compared to placebo, conducted in Muntinlupa City, The Philippines. Participants aged 6-23 months were enrolled and randomized to Vi-DT (25 µg) or placebo (0.9% sodium chloride) and evaluated for immunogenicity and overall safety 28 days post vaccination., Results: A total of 285 participants were enrolled and age-stratified: 6 to < 9 months, 9-12 months, and 13-23 months. Seventy-six (76) participants received Vi-DT and 19 received placebo per each strata. All participants seroconverted after a single dose of Vi-DT versus 7% of placebo recipients. Anti-Vi IgG GMT was 444.38 [95% CI (400.28; 493.34)] after a single dose of Vi-DT; there was no change in GMT after placebo administration, 0.41 [95% CI (0.33; 0.51), p < 0.0001]. A similar pattern of immunogenicity was reported across all age strata. The vaccine reported to be safe and well tolerated., Conclusions: Vi-DT vaccine was immunogenic, safe, and well tolerated in children aged 6-23 months. ClinicalTrials.gov registration number: NCT03527355., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflicts of Interest Maria Rosario Capeding received research grant. Seon-young Yang, Dong Soo Ham, Ji Hwa Ryu, and Hun Kim are employees of SK bioscience. Dr. Jerome Kim has consulted for Takeda and served as an unpaid consultant for GSK. All other authors declare having no conflict of interest., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A conference on «ARBOVIRUSES, A GLOBAL PUBLIC HEALTH THREAT» was organized on June 20-22, 2018 at the Merieux Foundation Conference Center in Veyrier du Lac, France, to review and raise awareness to the global public health threat of epidemic arboviruses, and to advance the discussion on the control and prevention of arboviral diseases. The presentations by scientists and public health officials from Asia, the Americas, Europe and Africa strengthened the notion that arboviral diseases of both humans and domestic animals are progressively becoming dominant public health problems in the world. The repeated occurrence of recent deadly epidemics strongly reinforces the call for action against these viral diseases, and the need for developing effective vaccines, drugs, vector control tools and strong prevention programs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020.)

CYD-TDV is a live, attenuated, tetravalent dengue vaccine licensed in 21 countries. We undertook a post-hoc analysis of the long-term efficacy of CYD-TDV during the surveillance expansion phase (SEP) of two Phase III studies (CYD14 in the Asia-Pacific region; CYD15 in Latin America). The SEP included approximately Year 5 and the entire Year 6 of follow-up after the first study injection. Vaccine efficacy against symptomatic virologically-confirmed dengue (VCD) was assessed by participant age (any age, ≥9, <9, 2-5, and 6-8 years at the time of the first injection) and baseline dengue serostatus using a case-cohort framework. Baseline dengue serostatus was estimated by several methods including logistic regression-based multiple imputation (MI) to predict PRNT 50 with key predictor being Month 13 (M13) anti-non-structural protein (NS1) titers; superlearner-based imputation by targeted minimum loss based estimation (TMLE); and M13 anti-NS1 titer threshold 9 EU/mL (NS1 M13). There were 436 symptomatic VCD cases (CYD14: n = 360; CYD15: n = 76) during the SEP. Vaccine efficacy in seropositive participants aged ≥9 years was assessed by MI (47.9% [95% CI 19.4; 66.3]), TMLE (53.0% [95% CI 23; 71]), and NS1 M13 (52.4% [95% CI 30.8; 67.3]). Vaccine efficacy estimates were lower in seropositive individuals aged <9 years compared with individuals ≥9 years. Among seropositive individuals aged 2-5 and 6-8 years, vaccine efficacy across the different approaches for assessing serostatus ranged from between -25.7 to 36.9% and 44.4 to 64.7% during the SEP, respectively. In the pooled CYD14/15 data of seronegatives, vaccine efficacy was null to modest. In conclusion, CYD-TDV was shown to maintain efficacy against symptomatic VCD in seropositive participants aged ≥9 years up to six years after the first dose. Persistence of efficacy was also observed in seropositive participants aged 6-8 years., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Sanofi Pasteur. Published by Elsevier Ltd.. All rights reserved.)

Background: Japanese encephalitis (JE) virus is the leading vaccine-preventable cause of encephalitis in Asia. For most travelers, JE risk is very low but varies based on several factors, including travel duration, location, and activities. To aid public health officials, health care providers, and travelers evaluate the worth of administering/ receiving pre-travel JE vaccinations, we estimated the numbers-needed-to-treat to prevent a case and the cost-effectiveness ratios of JE vaccination for U.S. travelers in different risk categories., Methods: We used a decision tree model to estimate cost per case averted from a societal and traveler perspective for hypothetical cohorts of vaccinated and unvaccinated travelers. Risk Category I included travelers planning to spend ≥1 month in JE-endemic areas, Risk Category II were shorter-term (<1 month) travelers spending ≥20% of their time doing outdoor activities in rural areas, and Risk Category III were all remaining travelers. We performed sensitivity analyses including examining changes in cost-effectiveness with 10- and 100-fold increases in incidence and medical treatment costs., Results: The numbers-needed-to-treat to prevent a case and cost per case averted were approximately 0.7 million and $0.6 billion for Risk Category I, 1.6 million and $1.2 billion for Risk Category II, and 9.8 million and $7.6 billion for Risk Category III. Increases of 10-fold and 100-fold in disease incidence proportionately decreased cost-effectiveness ratios. Similar levels of increases in medical treatment costs resulted in negligible changes in cost-effectiveness ratios., Conclusion: Numbers-needed-to-treat and cost-effectiveness ratios associated with preventing JE cases in U.S. travelers by vaccination varied greatly by risk category and disease incidence. While cost effectiveness ratios are not the sole rationale for decision-making regarding JE vaccination, the results presented here can aid in making such decisions under very different risk and cost scenarios., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Cholera has been eliminated as a public health problem in high-income countries that have implemented sanitation system separating the community's fecal waste from their drinking water and food supply. These expensive, highly-engineered systems, first developed in London over 150 years ago, have not reached low-income high-risk communities across Asia. Barriers to their implementation in communities at highest risk for cholera include the high capital and operating costs for this technological approach, limited capacity and perverse incentives of local governments, and a decreasing availability of water. Interim solutions including household level water treatment, constructing latrines and handwashing promotion have only marginally reduced the risk of cholera and other fecally transmitted diseases. Increased research to develop and policy flexibility to implement a new generation of solutions that are designed specifically to address the physical, financial and political constraints of low-income communities offers the best prospect for reducing the burden of cholera across Asia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The economic burden data can provide a basis to inform investments in cholera control and prevention activities. However, treatment costs and productivity loss due to cholera are not well studied., Methods: We included Asian countries that either reported cholera cases to the World Health Organization (WHO) in 2015 or were considered cholera endemic in 2015 global burden of disease study. Public health service delivery costs for hospitalization and outpatient costs, out-of-pocket costs to patients and households, and lost productivity were extracted from literature. A probabilistic multivariate sensitivity analysis was conducted for key outputs using Monte Carlo simulation. Scenario analyses were conducted using data from the WHO cholera reports and conservative and liberal disease burden estimates., Results: Our analysis included 14 Asian countries that were estimated to have a total of 850,000 cholera cases and 25,500 deaths in 2015 While, the WHO cholera report documented around 60,000 cholera cases and 28 deaths. We estimated around $20.2 million (I$74.4 million) in out-of-pocket expenditures, $8.5 million (I$30.1 million) in public sector costs, and $12.1 million (I$43.7 million) in lost productivity in 2015. Lost productivity due to premature deaths was estimated to be $985.7 million (I$3,638.6 million). Our scenario analyses excluding mortality costs showed that the economic burden ranged from 20.3% ($8.3 million) to 139.3% ($57.1 million) in high and low scenarios when compared to the base case scenario ($41 million) and was least at 10.1% ($4.1 million) when estimated based on cholera cases reported to WHO., Conclusion: The economic burden of cholera in Asia provides a better understanding of financial offsets that can be achieved, and the value of investments on cholera control measures. With a clear understanding of the limitations of the underlying assumptions, the information may be used in economic evaluations and policy decisions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cholera is an ancient disease that remains a public health problem in many impoverished locations around the world. Seven pandemics of cholera have been recorded since the first pandemic in 1817, the last of which is on going. Overcrowding, poverty, insufficient water and sanitation facilities increase the risk for cholera outbreaks. The epidemiology of cholera in the areas in Asia, Africa and the Americas where the disease occurs continues to evolve., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)