Effectiveness of Wolbachia-infected mosquito deployments in reducing the incidence of dengue and other Aedes-borne diseases in Niterói,Brazil: A quasi-experimental study

BackgroundThe introduction of the bacterium Wolbachia (wMel strain) into Aedes aegypti mosquitoes reduces their capacity to transmit dengue and other arboviruses. Evidence of a reduction in dengue case incidence following field releases of wMel-infected Ae. aegypti has been reported previously from a cluster randomised controlled trial in Indonesia, and quasi-experimental studies in Indonesia and northern Australia.Methodology/Principal findingsFollowing pilot releases in 2015–2016 and a period of intensive community engagement, deployments of adult wMel-infected Ae. aegypti mosquitoes were conducted in Niterói, Brazil during 2017–2019. Deployments were phased across four release zones, with a total area of 83 km² and a residential population of approximately 373,000. A quasi-experimental design was used to evaluate the effectiveness of wMel deployments in reducing dengue, chikungunya and Zika incidence. An untreated control zone was pre-defined, which was comparable to the intervention area in historical dengue trends. The wMel intervention effect was estimated by controlled interrupted time series analysis of monthly dengue, chikungunya and Zika case notifications to the public health surveillance system before, during and after releases, from release zones and the control zone. Three years after commencement of releases, wMel introgression into local Ae. aegypti populations was heterogeneous throughout Niterói, reaching a high prevalence (>80%) in the earliest release zone, and more moderate levels (prevalence 40–70%) elsewhere. Despite this spatial heterogeneity in entomological outcomes, the wMel intervention was associated with a 69% reduction in dengue incidence (95% confidence interval 54%, 79%), a 56% reduction in chikungunya incidence (95%CI 16%, 77%) and a 37% reduction in Zika incidence (95%CI 1%, 60%), in the aggregate release area compared with the pre-defined control area. This significant intervention effect on dengue was replicated across all four release zones, and in three of four zones for chikungunya, though not in individual release zones for Zika.Conclusions/SignificanceWe demonstrate that wMel Wolbachia can be successfully introgressed into Ae. aegypti populations in a large and complex urban setting, and that a significant public health benefit from reduced incidence of Aedes-borne disease accrues even where the prevalence of wMel in local mosquito populations is moderate and spatially heterogeneous. These findings are consistent with the results of randomised and non-randomised field trials in Indonesia and northern Australia, and are supportive of the Wolbachia biocontrol method as a multivalent intervention against dengue, chikungunya and Zika.     

Routine Pediatric Enterovirus 71 Vaccination in China: a Cost-Effectiveness Analysis

BackgroundChina accounted for 87% (9.8 million/11.3 million) of all hand, foot, and mouth disease (HFMD) cases reported to WHO during 2010–2014. Enterovirus 71 (EV71) is responsible for most of the severe HFMD cases. Three EV71 vaccines recently demonstrated good efficacy in children aged 6–71 mo. Here we assessed the cost-effectiveness of routine pediatric EV71 vaccination in China.ConclusionsCompared to no vaccination, routine pediatric EV71 vaccination would be very cost-effective in China if the cost of immunization (including all logistical, procurement, and administration costs needed to confer 5 y of vaccine protection) is below US$12.0–US$18.3, depending on the choice of vaccine among the three candidates. Given that the annual number of births in China has been around 16 million in recent years, the annual costs for routine pediatric EV71 vaccination at this cost range should not exceed US$192–US$293 million. Our results can be used to determine the optimal vaccine when the prices of the three vaccines are known.     

Cost-effectiveness and budget impact analyses of dengue vaccination in Indonesia

Despite the fact that the incidence and mortality rates due to dengue virus (DENV) infection in Indonesia are relatively high, dengue vaccination has not yet been introduced. This study aimed to analyse the cost-effectiveness and the budget impact of dengue vaccination in Indonesia by taking the potential of pre-vaccination screening into account. An age-structured decision tree model was developed to assess the cost-effectiveness value by applying a single cohort of 4,710,100 children that was followed-up in a 10-year time horizon within a 1-year analytical cycle. The budget impact was analysed in a 5-year period (2020–2024) by considering provinces’ readiness to introduce dengue vaccine and their incidence rate of DENV infection in the last 10 years. Vaccination that was coupled with pre-vaccination screening would reduce dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) by 188,142, 148,089 and 426 cases, respectively. It would save treatment cost at $23,433,695 and $14,091,642 from the healthcare and payer perspective, respectively. The incremental cost-effectiveness ratios (ICERs) would be $5,733 and $5,791 per quality-adjusted-life-year (QALY) gained from both perspectives. The most influential parameters affecting the ICERs were probability of DENV infection, vaccine efficacy, under-reporting factor, vaccine price, case fatality rate and screening cost. It can be concluded that dengue vaccination and pre-vaccination screening would be cost-effective to be implemented in Indonesia. Nevertheless, it seems unaffordable to be implemented since the total required cost for the nationwide vaccination would be 94.44% of routine immunization budget.     

Economic Analysis of Pandemic Influenza Vaccination Strategies in Singapore

Background

All influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares the economic outcomes of vaccination compared with treatment with antiviral agents alone, in Singapore.

Methodology

We analyzed the economic outcomes of pandemic vaccination (immediate vaccination and vaccine stockpiling) compared with treatment-only in Singapore using a decision-based model to perform cost-benefit and cost-effectiveness analyses. We also explored the annual insurance premium (willingness to pay) depending on the perceived risk of the next pandemic occurring.

Principal Findings

The treatment-only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is not cost-effective in most scenarios even with 100% vaccine effectiveness. The annual insurance premium was highest with immediate vaccination, and was lower with increased duration to the next pandemic. The premium was also higher with higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling with case-fatality rates of 0.4–0.6% would be cost-beneficial if vaccine effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost-beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant higher premiums than low-risk sub-groups.

Conclusions

The actual pandemic vaccine effectiveness and lead time is unknown. Vaccine strategy should be based on perception of severity. Immediate vaccination is most cost-effective, but requires vaccines to be available when required. Vaccine stockpiling as insurance against worst-case scenarios is also cost-effective. Research and development is therefore critical to develop and stockpile cheap, readily available effective vaccines.     

Economic impact of dengue illness and the cost-effectiveness of future vaccination programs in Singapore

Background

Dengue illness causes 50–100 million infections worldwide and threatens 2.5 billion people in the tropical and subtropical regions. Little is known about the disease burden and economic impact of dengue in higher resourced countries or the cost-effectiveness of potential dengue vaccines in such settings.

Methods and Findings

We estimate the direct and indirect costs of dengue from hospitalized and ambulatory cases in Singapore. We consider inter alia the impacts of dengue on the economy using the human-capital and the friction cost methods. Disease burden was estimated using disability-adjusted life years (DALYs) and the cost-effectiveness of a potential vaccine program was evaluated. The average economic impact of dengue illness in Singapore from 2000 to 2009 in constant 2010 US$ ranged between $0.85 billion and $1.15 billion, of which control costs constitute 42%–59%. Using empirically derived disability weights, we estimated an annual average disease burden of 9–14 DALYs per 100 000 habitants, making it comparable to diseases such as hepatitis B or syphilis. The proportion of symptomatic dengue cases detected by the national surveillance system was estimated to be low, and to decrease with age. Under population projections by the United Nations, the price per dose threshold for which vaccines stop being more cost-effective than the current vector control program ranged from $50 for mass vaccination requiring 3 doses and only conferring 10 years of immunity to $300 for vaccination requiring 2 doses and conferring lifetime immunity. The thresholds for these vaccine programs to not be cost-effective for Singapore were $100 and $500 per dose respectively.

Conclusions

Dengue illness presents a serious economic and disease burden in Singapore. Dengue vaccines are expected to be cost-effective if reasonably low prices are adopted and will help to reduce the economic and disease burden of dengue in Singapore substantially.     

Cost-effectiveness of dengue vaccination in Puerto Rico

An effective and widely used vaccine could reduce the burden of dengue virus (DENV) around the world. DENV is endemic in Puerto Rico, where the dengue vaccine CYD-TDV is currently under consideration as a control measure. CYD-TDV has demonstrated efficacy in clinical trials in vaccinees who had prior dengue virus infection. However, in vaccinees who had no prior dengue virus infection, the vaccine had a modestly elevated risk of hospitalization and severe disease. The WHO therefore recommended a strategy of pre-vaccination screening and vaccination of seropositive persons. To estimate the cost-effectiveness and benefits of this intervention (i.e., screening and vaccination of seropositive persons) in Puerto Rico, we simulated 10 years of the intervention in 9-year-olds using an agent-based model. Across the entire population, we found that 5.5% (4.6%-6.3%) of dengue hospitalizations could be averted. However, we also found that 0.057 (0.045–0.073) additional hospitalizations could occur for every 1,000 people in Puerto Rico due to DENV-naïve children who were vaccinated following a false-positive test results for prior exposure. The ratio of the averted hospitalizations among all vaccinees to additional hospitalizations among DENV-naïve vaccinees was estimated to be 19 (13–24). At a base case cost of vaccination of 382 USD, we found an incremental cost-effectiveness ratio of 122,000 USD per QALY gained. Our estimates can provide information for considerations to introduce the CYD-TDV vaccine in Puerto Rico.     

Vector competence of Aedes aegypti from Havana,Cuba, for dengue virus type 1, chikungunya,and Zika viruses

BackgroundLike many countries from the Americas, Cuba is threatened by Aedes aegypti-associated arboviruses such as dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viruses. Curiously, when CHIKV was actively circulating in the region in 2013–2014, no autochthonous transmission of this virus was detected in Havana, Cuba, despite the importation of chikungunya cases into this city. To investigate if the transmission ability of local mosquito populations could explain this epidemiological scenario, we evaluated for the first time the vector competence of two Ae. aegypti populations (Pasteur and Párraga) collected from Havana for dengue virus type 1 (DENV-1), CHIKV, and ZIKV.Methodology/Principal findingsMosquito populations were fed separately using blood containing ZIKV, DENV-1, or CHIKV. Infection, dissemination, and transmission rates, were estimated at 3 (exclusively for CHIKV), 7, and 14 days post exposure (dpe) for each Ae. aegypti population-virus combination. Both mosquito populations were susceptible to DENV-1 and ZIKV, with viral infection and dissemination rates ranging from 24–97% and 6–67% respectively. In addition, CHIKV disseminated in both populations and was subsequently transmitted. Transmission rates were low (<30%) regardless of the mosquito population/virus combination and no ZIKV was detected in saliva of females from the Pasteur population at any dpe.Conclusions/SignificanceOur study demonstrated the ability of Ae. aegypti from Cuba to transmit DENV, ZIKV, and CHIKV. These results, along with the widespread distribution and high abundance of this species in the urban settings throughout the island, highlight the importance of Ae. aegypti control and arbovirus surveillance to prevent future outbreaks.     

Cost-Effectiveness of Vaccinating Immunocompetent ≥65 Year Olds with the 13-Valent Pneumococcal Conjugate Vaccine in England

Background

Recently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7) since 2006 and PCV13 since 2010), as well as a 23-valent pneumococcal polysaccharide (PPV23) vaccination programme targeting clinical risk-groups and those ≥65 years.

Method

A static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results.

Results

The childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP), and using recent measures of vaccine efficacy against these endpoints for ≥65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs) and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust.

Conclusions

Vaccinating immunocompetent individuals aged ≥65 years with PCV13 is efficacious. However the absolute incidence of vaccine-type disease will likely become very low due to wider benefits of the childhood PCV13 vaccination programme, such that a specific PCV13 vaccination programme targeting the immunocompetent elderly would not be cost-effective.     

Zika Virus,a New Threat for Europe?

BackgroundSince its emergence in 2007 in Micronesia and Polynesia, the arthropod-borne flavivirus Zika virus (ZIKV) has spread in the Americas and the Caribbean, following first detection in Brazil in May 2015. The risk of ZIKV emergence in Europe increases as imported cases are repeatedly reported. Together with chikungunya virus (CHIKV) and dengue virus (DENV), ZIKV is transmitted by Aedes mosquitoes. Any countries where these mosquitoes are present could be potential sites for future ZIKV outbreak. We assessed the vector competence of European Aedes mosquitoes (Aedes aegypti and Aedes albopictus) for the currently circulating Asian genotype of ZIKV.Conclusions/SignificanceIn combination with the restricted distribution of European Ae. albopictus, our results on vector competence corroborate the low risk for ZIKV to expand into most parts of Europe with the possible exception of the warmest regions bordering the Mediterranean coastline.     

Effectiveness of Ultra-Low Volume Nighttime Applications of an Adulticide against Diurnal Aedes albopictus,a Critical Vector of Dengue and Chikungunya Viruses

Aedes albopictus, the Asian tiger mosquito, continues expanding its geographic range and involvement in mosquito-borne diseases such as chikungunya and dengue. Vector control programs rarely attempt to suppress this diurnal species with an ultra-low volume (ULV) adulticide because for maximum efficacy applications are conducted at night. During 2009–2011 we performed experimental nighttime applications of a novel adulticide (DUET®) against field populations of Ae. albopictus within an urban site composed of approximately 1,000 parcels (home and yard) in northeastern USA. Dual applications at mid label rate of the adulticide spaced one or two days apart accomplished significantly higher control (85.0±5.4% average reduction) than single full rate applications (73.0±5.4%). Our results demonstrate that nighttime ULV adulticiding is effective in reducing Ae. albopictus abundance and highlight its potential for use as part of integrated pest management programs and during disease epidemics when reducing human illness is of paramount importance.     

Effectiveness of the 10-Valent Pneumococcal Conjugate Vaccine (PCV-10) in Children in Chile: A Nested Case-Control Study Using Nationwide Pneumonia Morbidity and Mortality Surveillance Data

BackgroundThe ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Chilean National Immunization Program (NIP) in January 2011 with a 3+1 schedule (2, 4, 6 and 12 months) without catch-up vaccination. We evaluated the effectiveness of PCV10 on pneumonia morbidity and mortality among infants during the first two years after vaccine introduction.MethodsThis is a population-based nested case-control study using four merged nationwide case-based electronic health data registries: live birth, vaccination, hospitalization and mortality. Children born in 2010 and 2011 were followed from two moths of age for a period of two years. Using four different case definitions of pneumonia hospitalization and/or mortality (all-cause and pneumonia related deaths), all cases and four randomly selected matched controls per case were selected. Controls were matched to cases on analysis time. Vaccination status was then assessed. Vaccine effectiveness (VE) was estimated using conditional logistic regression.ResultsThere were a total of 497,996 children in the 2010 and 2011 Chilean live-birth cohorts. PCV10 VE was 11.2% (95%CI 8.5–13.6) when all pneumonia hospitalizations and deaths were used to define cases. VE increased to 20.7 (95%CI 17.3–23.8) when ICD10 codes used to denote viral pneumonia were excluded from the case definition. VE estimates on pneumonia deaths and all-cause deaths were 71.5 (95%CI 9.0–91.8) and 34.8 (95% CI 23.7–44.4), respectively.ConclusionPCV10 vaccination substantially reduced the number of hospitalizations due to pneumonia and deaths due to pneumonia and to all-causes over this study period. Our findings also reinforce the importance of having quality health information systems for measuring VE.     

Estimated impact of RTS,S/AS01 malaria vaccine allocation strategies in sub-Saharan Africa: A modelling study

BackgroundThe RTS,S/AS01 vaccine against Plasmodium falciparum malaria infection completed phase III trials in 2014 and demonstrated efficacy against clinical malaria of approximately 36% over 4 years for a 4-dose schedule in children aged 5–17 months. Pilot vaccine implementation has recently begun in 3 African countries. If the pilots demonstrate both a positive health impact and resolve remaining safety concerns, wider roll-out could be recommended from 2021 onwards. Vaccine demand may, however, outstrip initial supply. We sought to identify where vaccine introduction should be prioritised to maximise public health impact under a range of supply constraints using mathematical modelling.Methods and findingsUsing a mathematical model of P. falciparum malaria transmission and RTS,S vaccine impact, we estimated the clinical cases and deaths averted in children aged 0–5 years in sub-Saharan Africa under 2 scenarios for vaccine coverage (100% and realistic) and 2 scenarios for other interventions (current coverage and World Health Organization [WHO] Global Technical Strategy targets). We used a prioritisation algorithm to identify potential allocative efficiency gains from prioritising vaccine allocation among countries or administrative units to maximise cases or deaths averted. If malaria burden at introduction is similar to current levels—assuming realistic vaccine coverage and country-level prioritisation in areas with parasite prevalence >10%—we estimate that 4.3 million malaria cases (95% credible interval [CrI] 2.8–6.8 million) and 22,000 deaths (95% CrI 11,000–35,000) in children younger than 5 years could be averted annually at a dose constraint of 30 million. This decreases to 3.0 million cases (95% CrI 2.0–4.7 million) and 14,000 deaths (95% CrI 7,000–23,000) at a dose constraint of 20 million, and increases to 6.6 million cases (95% CrI 4.2–10.8 million) and 38,000 deaths (95% CrI 18,000–61,000) at a dose constraint of 60 million. At 100% vaccine coverage, these impact estimates increase to 5.2 million cases (95% CrI 3.5–8.2 million) and 27,000 deaths (95% CrI 14,000–43,000), 3.9 million cases (95% CrI 2.7–6.0 million) and 19,000 deaths (95% CrI 10,000–30,000), and 10.0 million cases (95% CrI 6.7–15.7 million) and 51,000 deaths (95% CrI 25,000–82,000), respectively. Under realistic vaccine coverage, if the vaccine is prioritised sub-nationally, 5.3 million cases (95% CrI 3.5–8.2 million) and 24,000 deaths (95% CrI 12,000–38,000) could be averted at a dose constraint of 30 million. Furthermore, sub-national prioritisation would allow introduction in almost double the number of countries compared to national prioritisation (21 versus 11). If vaccine introduction is prioritised in the 3 pilot countries (Ghana, Kenya, and Malawi), health impact would be reduced, but this effect becomes less substantial (change of <5%) if 50 million or more doses are available. We did not account for within-country variation in vaccine coverage, and the optimisation was based on a single outcome measure, therefore this study should be used to understand overall trends rather than guide country-specific allocation.ConclusionsThese results suggest that the impact of constraints in vaccine supply on the public health impact of the RTS,S malaria vaccine could be reduced by introducing the vaccine at the sub-national level and prioritising countries with the highest malaria incidence.

Alexandra Hogan and colleagues explore strategies to optimize vaccine allocation for maximum public health benefit in the face of potential supply constraints.     

piggybac- and PhiC31-Mediated Genetic Transformation of the Asian Tiger Mosquito,Aedes albopictus (Skuse)

Background

The Asian tiger mosquito, Aedes albopictus (Skuse), is a vector of several arboviruses including dengue and chikungunya. This highly invasive species originating from Southeast Asia has travelled the world in the last 30 years and is now established in Europe, North and South America, Africa, the Middle East and the Caribbean. In the absence of vaccine or antiviral drugs, efficient mosquito control strategies are crucial. Conventional control methods have so far failed to control Ae. albopictus adequately.

Methodology/Principal Findings

Germline transformation of Aedes albopictus was achieved by micro-injection of embryos with a piggyBac-based transgene carrying a 3xP3-ECFP marker and an attP site, combined with piggyBac transposase mRNA and piggyBac helper plasmid. Five independent transgenic lines were established, corresponding to an estimated transformation efficiency of 2–3%. Three lines were re-injected with a second-phase plasmid carrying an attB site and a 3xP3-DsRed2 marker, combined with PhiC31 integrase mRNA. Successful site-specific integration was observed in all three lines with an estimated transformation efficiency of 2–6%.

Conclusions/Significance

Both piggybac- and site-specific PhiC31-mediated germline transformation of Aedes albopictus were successfully achieved. This is the first report of Ae. albopictus germline transformation and engineering, a key step towards studying and controlling this species using novel molecular techniques and genetic control strategies.     

Economic Evaluation of Immunisation Programme of 23-Valent Pneumococcal Polysaccharide Vaccine and the Inclusion of 13-Valent Pneumococcal Conjugate Vaccine in the List for Single-Dose Subsidy to the Elderly in Japan

BackgroundCurrently in Japan, both 23-valent pneumococcal polysaccharide vaccine (PPSV–23) and 13-valent pneumococcal conjugate vaccine (PCV–13) are available for the elderly for the prevention of S. pneumoniae-related diseases. PPSV–23 was approved in 1988, while the extended use of PCV–13 was approved for adults aged 65 and older in June 2014. Despite these two vaccines being available, the recently launched national immunisation programme for the elderly only subsidised PPSV–23. The framework of the current immunisation programme lasts for five years. The elderly population eligible for the subsidised PPSV–23 shot for the 1st year are those aged 65, 70, 75, 80, 85, 90, 95 and ≥100. While from the 2nd year to the 5th year, those who will age 65, 70, 75, 80, 85, 90, 95 and 100 will receive the same subsidised shot.MethodsWe performed economic evaluations to (1) evaluate the efficiency of alternative strategies of PPSV–23 single-dose immunisation programme, and (2) investigate the efficiency of PCV–13 inclusion in the list for single-dose pneumococcal vaccine immunisation programme. Three alternative strategies were created in this study, namely: (1) current PPSV–23 strategy, (2) 65 to 80 (as “65–80 PPSV–23 strategy”), and (3) 65 and older (as “≥65 PPSV–23 strategy”). We constructed a Markov model depicting the S. pneumoniae-related disease course pathways. The transition probabilities, utility weights to estimate quality adjusted life year (QALY) and disease treatment costs were either calculated or cited from literature. Cost of per shot of vaccine was ¥8,116 (US$74; US$1 = ¥110) for PPSV–23 and ¥10,776 (US$98) for PCV–13. The model runs for 15 years with one year cycle after immunisation. Discounting was at 3%.ResultsCompared to current PPSV–23 strategy, 65–80 PPSV–23 strategy cost less but gained less, while the incremental cost-effectiveness ratios (ICERs) of ≥65 PPSV–23 strategy was ¥5,025,000 (US$45,682) per QALY gained. PCV–13 inclusion into the list for single-dose subsidy has an ICER of ¥377,000 (US$3,427) per QALY gained regardless of the PCV–13 diffusion level. These ICERs were found to be cost-effective since they are lower than the suggested criterion by WHO of three times GDP (¥11,000,000 or US$113,636 per QALY gained), which is the benchmark used in judging the cost-effectiveness of an immunisation programmne.ConclusionsThe results suggest that switching current PPSV–23 strategy to ≥65 PPSV–23 strategy or including PCV–13 into the list for single-dose subsidy to the elderly in Japan has value for money.     

Seroepidemiological study of Japanese encephalitis virus in Chiang Mai: Immunity and susceptibility 28 years after introduction of a vaccination programme

BackgroundThailand has introduced a nationwide vaccination against Japanese encephalitis virus (JEV) into National Immunization Programme since the 1990’s. To improve the understanding of immunity and susceptibility of the population after 28 years of a vaccination programme, we conducted a JEV seroepidemiological study in a JEV-endemic area of Thailand.MethodsAn age-stratified, population-based, seroepidemiological study was conducted in Chiang Mai, Thailand–a northern Thai province where is an endemic area of Japanese encephalitis. Nine districts were chosen based on administrative definition: rural (n = 3); urban (n = 3); and peri-urban (n = 3). Within each district, eligible participants were randomly selected from 3 age groups: adolescents (10–20 years); adults (21–50 years); and older adults/elderly (≥51 years) by computer randomization. Plaque reduction neutralization tests (PRNT₅₀ and PRNT₉₀) were performed to measure neutralizing antibodies to JEV. To account for the cross-reactivity of JEV and other flaviviruses, JEV seroprotection was defined according to age, previous history of JEV vaccination, and PRNT₅₀/PRNT₉₀ levels of study participants.ResultsOverall, 279 adolescents, 297 adults, and 297 older adults/elderly were enrolled from nine districts. Age-stratified, protocol-defined, cluster-adjusted JEV seroprotection rates were 61% (95% CI: 48–73%), 43% (95% CI: 31–57%), and 52% (95% CI: 37–67%) for adolescents, adults, and older adults/elderly, respectively. Living in peri-urban districts, having a history of prior dengue virus infection, and previously receiving mouse brain-derived JEV vaccine were significantly associated with seroprotection to JEV in adolescents. Older age and male sex were associated with seroprotection for adults; and only male sex was the associated factor for older adults/elderly (P <0.05).ConclusionsApproximately half of population living in a JEV-endemic area demonstrated seroprotection to JEV. Ongoing nationwide surveillance on JEV seropepidemiology is an important strategy to understand the evolving population-level immunity to JEV, and to help formulating the appropriate recommendations on JE immunization.     

Climatic and socio-economic factors supporting the co-circulation of dengue,Zika and chikungunya in three different ecosystems in Colombia

Dengue, Zika and chikungunya are diseases of global health significance caused by arboviruses and transmitted by the mosquito Aedes aegypti, which is of worldwide circulation. The arrival of the Zika and chikungunya viruses to South America increased the complexity of transmission and morbidity caused by these viruses co-circulating in the same vector mosquito species. Here we present an integrated analysis of the reported arbovirus cases between 2007 and 2017 and local climate and socio-economic profiles of three distinct Colombian municipalities (Bello, Cúcuta and Moniquirá). These locations were confirmed as three different ecosystems given their contrasted geographic, climatic and socio-economic profiles. Correlational analyses were conducted with both generalised linear models and generalised additive models for the geographical data. Average temperature, minimum temperature and wind speed were strongly correlated with disease incidence. The transmission of Zika during the 2016 epidemic appeared to decrease circulation of dengue in Cúcuta, an area of sustained high incidence of dengue. Socio-economic factors such as barriers to health and childhood services, inadequate sanitation and poor water supply suggested an unfavourable impact on the transmission of dengue, Zika and chikungunya in all three ecosystems. Socio-demographic influencers were also discussed including the influx of people to Cúcuta, fleeing political and economic instability from neighbouring Venezuela. Aedes aegypti is expanding its range and increasing the global threat of these diseases. It is therefore vital that we learn from the epidemiology of these arboviruses and translate it into an actionable local knowledge base. This is even more acute given the recent historical high of dengue cases in the Americas in 2019, preceding the COVID-19 pandemic, which is itself hampering mosquito control efforts.     

Understanding COVID-19 vaccine demand and hesitancy: A nationwide online survey in China

BackgroundThis study attempts to understand coronavirus disease 2019 (COVID-19) vaccine demand and hesitancy by assessing the public’s vaccination intention and willingness-to-pay (WTP). Confidence in COVID-19 vaccines produced in China and preference for domestically-made or foreign-made vaccines was also investigated.MethodsA nationwide cross-sectional, self-administered online survey was conducted on 1–19 May 2020. The health belief model (HBM) was used as a theoretical framework for understanding COVID-19 vaccination intent and WTP.ResultsA total of 3,541 complete responses were received. The majority reported a probably yes intent (54.6%), followed by a definite yes intent (28.7%). The perception that vaccination decreases the chances of getting COVID-19 under the perceived benefit construct (OR = 3.14, 95% CI 2.05–4.83) and not being concerned about the efficacy of new COVID-19 vaccines under the perceived barriers construct (OR = 1.65, 95% CI 1.31–2.09) were found to have the highest significant odds of a definite intention to take the COVID-19 vaccine. The median (interquartile range [IQR]) of WTP for COVID-19 vaccine was CNY¥200/US$28 (IQR CNY¥100–500/USD$14–72). The highest marginal WTP for the vaccine was influenced by socio-economic factors. The majority were confident (48.7%) and completely confident (46.1%) in domestically-made COVID-19 vaccine. 64.2% reported a preference for a domestically-made over foreign-made COVID-19 vaccine.ConclusionsThe findings demonstrate the utility of HBM constructs in understanding COVID-19 vaccination intent and WTP. It is important to improve health promotion and reduce the barriers to COVID-19 vaccination.     

The role of urbanisation in the spread of Aedes mosquitoes and the diseases they transmit—A systematic review

BackgroundThis systematic review aims to assess how different urbanisation patterns related to rapid urban growth, unplanned expansion, and human population density affect the establishment and distribution of Aedes aegypti and Aedes albopictus and create favourable conditions for the spread of dengue, chikungunya, and Zika viruses.Methods and findingsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted using the PubMed, Virtual Health Library, Cochrane, WHO Library Database (WHOLIS), Google Scholar, and and the Institutional Repository for Information Sharing (IRIS) databases. From a total of 523 identified studies, 86 were selected for further analysis, and 29 were finally analysed after applying all inclusion and exclusion criteria. The main explanatory variables used to associate urbanisation with epidemiological/entomological outcomes were the following: human population density, urban growth, artificial geographical space, urban construction, and urban density. Associated with the lack of a global definition of urbanisation, several studies provided their own definitions, which represents one of the study’s limitations. Results were based on 8 ecological studies/models, 8 entomological surveillance studies, 7 epidemiological surveillance studies, and 6 studies consisting of spatial and predictive models. According to their focus, studies were categorised into 2 main subgroups, namely “Aedes ecology” and “transmission dynamics.” There was a consistent association between urbanisation and the distribution and density of Aedes mosquitoes in 14 of the studies and a strong relationship between vector abundance and disease transmission in 18 studies. Human population density of more than 1,000 inhabitants per square kilometer was associated with increased levels of arboviral diseases in 15 of the studies.ConclusionsThe use of different methods in the included studies highlights the interplay of multiple factors linking urbanisation with ecological, entomological, and epidemiological parameters and the need to consider a variety of these factors for designing effective public health approaches.     

Assessment of Health Benefits and Cost-Effectiveness of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccination in Kenyan Children

Background

The GAVI Alliance supported10-valent pneumococcal conjugate vaccine (PCV10) introduction in Kenya. We estimated the cost-effectiveness of introducing either PCV10 or the13-valent vaccine (PCV13) from a societal perspective and explored the incremental impact of including indirect vaccine effects.

Methods

The costs and effects of pneumococcal vaccination among infants born in Kenya in 2010 were assessed using a decision analytic model comparing PCV10 or PCV13, in turn, with no vaccination. Direct vaccine effects were estimated as a reduction in the incidence of pneumococcal meningitis, sepsis, bacteraemic pneumonia and non-bacteraemic pneumonia. Pneumococcal disease incidence was extrapolated from a population-based hospital surveillance system in Kilifi and adjustments were made for variable access to care across Kenya. We used vaccine efficacy estimates from a trial in The Gambia and accounted for serotype distribution in Kilifi. We estimated indirect vaccine protection and serotype replacement by extrapolating from the USA. Multivariable sensitivity analysis was conducted using Monte Carlo simulation. We assumed a vaccine price of US$ 3.50 per dose.

Findings

The annual cost of delivering PCV10 was approximately US$14 million. We projected a 42.7% reduction in pneumococcal disease episodes leading to a US$1.97 million reduction in treatment costs and a 6.1% reduction in childhood mortality annually. In the base case analysis, costs per discounted DALY and per death averted by PCV10, amounted to US$ 59 (95% CI 26–103) and US$ 1,958 (95% CI 866–3,425), respectively. PCV13 introduction improved the cost-effectiveness ratios by approximately 20% and inclusion of indirect effects improved cost-effectiveness ratios by 43–56%. The break-even prices for introduction of PCV10 and PCV13 are US$ 0.41 and 0.51, respectively.

Conclusions

Introducing either PCV10 or PCV13 in Kenya is highly cost-effective from a societal perspective. Indirect effects, if they occur, would significantly improve the cost-effectiveness.     

The potential economic value of a Trypanosoma cruzi (Chagas disease) vaccine in Latin America

Background

Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), is the leading etiology of non-ischemic heart disease worldwide, with Latin America bearing the majority of the burden. This substantial burden and the limitations of current interventions have motivated efforts to develop a vaccine against T. cruzi.

Methodology/Principal Findings

We constructed a decision analytic Markov computer simulation model to assess the potential economic value of a T. cruzi vaccine in Latin America from the societal perspective. Each simulation run calculated the incremental cost-effectiveness ratio (ICER), or the cost per disability-adjusted life year (DALY) avoided, of vaccination. Sensitivity analyses evaluated the impact of varying key model parameters such as vaccine cost (range: $0.50–$200), vaccine efficacy (range: 25%–75%), the cost of acute-phase drug treatment (range: $10–$150 to account for variations in acute-phase treatment regimens), and risk of infection (range: 1%–20%). Additional analyses determined the incremental cost of vaccinating an individual and the cost per averted congestive heart failure case. Vaccination was considered highly cost-effective when the ICER was ≤1 times the GDP/capita, still cost-effective when the ICER was between 1 and 3 times the GDP/capita, and not cost-effective when the ICER was >3 times the GDP/capita. Our results showed vaccination to be very cost-effective and often economically dominant (i.e., saving costs as well providing health benefits) for a wide range of scenarios, e.g., even when risk of infection was as low as 1% and vaccine efficacy was as low as 25%. Vaccinating an individual could likely provide net cost savings that rise substantially as risk of infection or vaccine efficacy increase.

Conclusions/Significance

Results indicate that a T. cruzi vaccine could provide substantial economic benefit, depending on the cost of the vaccine, and support continued efforts to develop a human vaccine.