Prevention and control of dengue and chikungunya in Colombia: A cost-effectiveness analysis

BackgroundChikungunya and dengue are emerging diseases that have caused large outbreaks in various regions of the world. Both are both spread by Aedes aegypti and Aedes albopictus mosquitos. We developed a dynamic transmission model of chikungunya and dengue, calibrated to data from Colombia (June 2014 –December 2017).Methodology/Principal findingsWe evaluated the health benefits and cost-effectiveness of residual insecticide treatment, long-lasting insecticide-treated nets, routine dengue vaccination for children aged 9, catchup vaccination for individuals aged 10–19 or 10–29, and portfolios of these interventions. Model calibration resulted in 300 realistic transmission parameters sets that produced close matches to disease-specific incidence and deaths. Insecticide was the preferred intervention and was cost-effective. Insecticide averted an estimated 95 chikungunya cases and 114 dengue cases per 100,000 people, 61 deaths, and 4,523 disability-adjusted life years (DALYs). In sensitivity analysis, strategies that included dengue vaccination were cost-effective only when the vaccine cost was 14% of the current price.Conclusions/SignificanceInsecticide to prevent chikungunya and dengue in Colombia could generate significant health benefits and be cost-effective. Because of limits on diagnostic accuracy and vaccine efficacy, the cost of dengue testing and vaccination must decrease dramatically for such vaccination to be cost-effective in Colombia. The vectors for chikungunya and dengue have recently spread to new regions, highlighting the importance of understanding the effectiveness and cost-effectiveness of policies aimed at preventing these diseases.     

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.     

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.     

Dengue,Zika, and Chikungunya viral circulation and hospitalization rates in Brazil from 2014 to 2019: An ecological study

BackgroundIn addition to their direct pathogenic effects, arthropod-borne (arboviruses) have been hypothesized to indirectly contribute to hospitalizations and death through decompensation of pre-existing comorbidities. Using nationwide data routinely collected from 1 January 2014 to 31 December 2019 in Brazil, we investigated whether local increases in arbovirus notifications were associated with excess hospitalization.MethodsWe estimated the relative risks for the association between municipality- and state-level increases in arboviral case notifications and age-standardized hospitalization rates (i.e., classified as direct or indirect based on ICD-10 codes) using Bayesian multilevel models with random effects accounting for temporal and geographic correlations. For municipality-level analyses, we excluded municipalities with <200 notifications of a given arbovirus and further adjusted the models for the local Gini Index, Human Development Index, and Family Healthcare Strategy (Estratégia de Saúde da Família) coverage. Models for dengue, Zika, and chikungunya were performed separately.ResultsFrom 2014 to 2019, Brazil registered 7,566,330 confirmed dengue cases, 159,029 confirmed ZIKV cases, and 433,887 confirmed CHIKV cases. Dengue notifications have an endemic and seasonal pattern, with cases present in 5334 of the 5570 (95.8%) Brazilian municipalities and most (69.5%) registered between February and May. Chikungunya notifications followed a similar seasonal pattern to DENV but with a smaller incidence and were restricted to 4390 (78.8%) municipalities. ZIKV was only notified in 2581 (46.3%) municipalities. Increases in dengue and chikungunya notifications were associated with small increases in age-standardized arbovirus-related hospitalizations, but no consistent association was found with all-cause or other specific indirect causes of hospitalization. Zika was associated to increases in hospitalizations by neurological diseases.ConclusionsAlthough we found no clear association between increased incidence of the three arboviruses and excess risks of all-cause or indirect hospitalizations at the municipality- and state-levels, follow-up investigations at the individual-level are warranted to define any potential role of acute arbovirus infection in exacerbating risks of hospitalization from underlying conditions.     

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.     

Assessing the reporting of Dengue,Chikungunya and Zika to the National Surveillance System in Colombia from 2014–2017: A Capture-recapture analysis accounting for misclassification of arboviral diagnostics

BackgroundChikungunya, dengue, and Zika are three different arboviruses which have similar symptoms and are a major public health issue in Colombia. Despite the mandatory reporting of these arboviruses to the National Surveillance System in Colombia (SIVIGILA), it has been reported that the system captures less than 10% of diagnosed cases in some cities.Methodology/Principal findingsTo assess the scope and degree of arboviruses reporting in Colombia between 2014–2017, we conducted an observational study of surveillance data using the capture-recapture approach in three Colombian cities. Using healthcare facility registries (capture data) and surveillance-notified cases (recapture data), we estimated the degree of reporting by clinical diagnosis. We fit robust Poisson regressions to identify predictors of reporting and estimated the predicted probability of reporting by disease and year. To account for the potential misclassification of the clinical diagnosis, we used the simulation extrapolation for misclassification (MC-SIMEX) method. A total of 266,549 registries were examined. Overall arboviruses’ reporting ranged from 5.3% to 14.7% and varied in magnitude according to age and year of diagnosis. Dengue was the most notified disease (21–70%) followed by Zika (6–45%). The highest reporting rate was seen in 2016, an epidemic year. The MC-SIMEX corrected rates indicated underestimation of the reporting due to the potential misclassification bias.ConclusionsThese findings reflect challenges on arboviruses’ reporting, and therefore, potential challenges on the estimation of arboviral burden in Colombia and other endemic settings with similar surveillance systems.     

Early warning systems (EWSs) for chikungunya,dengue, malaria,yellow fever,and Zika outbreaks: What is the evidence? A scoping review

BackgroundEarly warning systems (EWSs) are of increasing importance in the context of outbreak-prone diseases such as chikungunya, dengue, malaria, yellow fever, and Zika. A scoping review has been undertaken for all 5 diseases to summarize existing evidence of EWS tools in terms of their structural and statistical designs, feasibility of integration and implementation into national surveillance programs, and the users’ perspective of their applications.MethodsData were extracted from Cochrane Database of Systematic Reviews (CDSR), Google Scholar, Latin American and Caribbean Health Sciences Literature (LILACS), PubMed, Web of Science, and WHO Library Database (WHOLIS) databases until August 2019. Included were studies reporting on (a) experiences with existing EWS, including implemented tools; and (b) the development or implementation of EWS in a particular setting. No restrictions were applied regarding year of publication, language or geographical area.FindingsThrough the first screening, 11,710 documents for dengue, 2,757 for Zika, 2,706 for chikungunya, 24,611 for malaria, and 4,963 for yellow fever were identified. After applying the selection criteria, a total of 37 studies were included in this review. Key findings were the following: (1) a large number of studies showed the quality performance of their prediction models but except for dengue outbreaks, only few presented statistical prediction validity of EWS; (2) while entomological, epidemiological, and social media alarm indicators are potentially useful for outbreak warning, almost all studies focus primarily or exclusively on meteorological indicators, which tends to limit the prediction capacity; (3) no assessment of the integration of the EWS into a routine surveillance system could be found, and only few studies addressed the users’ perspective of the tool; (4) almost all EWS tools require highly skilled users with advanced statistics; and (5) spatial prediction remains a limitation with no tool currently able to map high transmission areas at small spatial level.ConclusionsIn view of the escalating infectious diseases as global threats, gaps and challenges are significantly present within the EWS applications. While some advanced EWS showed high prediction abilities, the scarcity of tool assessments in terms of integration into existing national surveillance systems as well as of the feasibility of transforming model outputs into local vector control or action plans tends to limit in most cases the support of countries in controlling disease outbreaks.     

Co-circulation and misdiagnosis led to underestimation of the 2015–2017 Zika epidemic in the Americas

During the 2015–2017 Zika epidemic, dengue and chikungunya–two other viral diseases with the same vector as Zika–were also in circulation. Clinical presentation of these diseases can vary from person to person in terms of symptoms and severity, making it difficult to differentially diagnose them. Under these circumstances, it is possible that numerous cases of Zika could have been misdiagnosed as dengue or chikungunya, or vice versa. Given the importance of surveillance data for informing epidemiological analyses, our aim was to quantify the potential extent of misdiagnosis during this epidemic. Using basic principles of probability and empirical estimates of diagnostic sensitivity and specificity, we generated revised estimates of reported cases of Zika that accounted for the accuracy of diagnoses made on the basis of clinical presentation with or without laboratory confirmation. Applying this method to weekly reported case data from 43 countries throughout Latin America and the Caribbean, we estimated that 944,700 (95% CrI: 884,900–996,400) Zika cases occurred when assuming all confirmed cases were diagnosed using molecular methods versus 608,400 (95% CrI: 442,000–821,800) Zika cases that occurred when assuming all confirmed cases were diagnosed using serological methods. Our results imply that misdiagnosis was more common in countries with proportionally higher reported cases of dengue and chikungunya, such as Brazil. Given that Zika, dengue, and chikungunya appear likely to co-circulate in the Americas and elsewhere for years to come, our methodology has the potential to enhance the interpretation of passive surveillance data for these diseases going forward. Likewise, our methodology could also be used to help resolve transmission dynamics of other co-circulating diseases with similarities in symptomatology and potential for misdiagnosis.     

A recent chikungunya outbreak associated with the occurrence of Aedes vectors (Diptera: Culicidae) in Kassala state,eastern Sudan in 2018

Aedes aegypti and Ae. albopictus (Diptera: Culicidae) are primary vectors of human arboviral diseases such as dengue, chikungunya, yellow fever, and Zika viruses. Aedes aegypti is well distributed in Sudan, except in Northern and Khartoum states, while Ae. albopictus has not been previously reported. Recently, Eastern Sudan witnessed an unprecedented large outbreak of chikungunya fever between 31 May 2018 and 30 March 2019. The outbreak was composed of four waves; one of them was in Kassala state. Aedes survey in localities of Kassala state (rather than Kassala city) is carried out to assess the possible expansion of the disease in the state. The results showed the presence of immature stages of Aedes spp. in four localities from ten localities. From the four localities that recorded Aedes spp., two localities (Rural Kassala and West Kassala) were reported with chikungunya cases. From this investigation, Ae. albopictus was reported for the first time in Sudan. Also, this investigation showed the importance of conducting entomological surveys with epidemiological surveys during outbreaks of arboviral diseases.     

Evaluation of the public health risk for autochthonous transmission of mosquito-borne viruses in southern Switzerland

Epidemics of mosquito-borne diseases such as chikungunya and dengue fever are becoming more frequent around the world. In Switzerland, autochthonous cases have not been reported so far, although the presence of the vector Aedes albopictus in urban areas of southern Switzerland increases the risk of indigenous transmissions subsequent to imported cases. In 2018, the potential risk of an outbreak of arboviral diseases was assessed in five municipalities of southern Switzerland. The population abundance of Ae. albopictus was evaluated during the mosquito active season by the mean number of Ae. albopictus bites per day per person (estimated using the human landing collection method) and the risk of outbreak in the case of the introduction of chikungunya, dengue or Zika viruses was estimated. In the five localities investigated, no epidemic risk appeared to be present for any of the arboviruses taken into consideration in the initial months (i.e. mid-May to end of July) of Ae. albopictus activity. In the case of the introduction of chikungunya (mutated or not), dengue (serotype 1) or Zika (African lineage) viruses during mid-end August, an epidemic could have occurred in all the municipalities investigated. In mid-end September, the introduction of same arboviruses could have led to an epidemic in three of the five municipalities investigated.     

The Aedes aegypti siRNA pathway mediates broad-spectrum defense against human pathogenic viruses and modulates antibacterial and antifungal defenses

The mosquito’s innate immune system defends against a variety of pathogens, and the conserved siRNA pathway plays a central role in the control of viral infections. Here, we show that transgenic overexpression of Dicer2 (Dcr2) or R2d2 resulted in an accumulation of 21-nucleotide viral sequences that was accompanied by a significant suppression of dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) replication, thus indicating the broad-spectrum antiviral response mediated by the siRNA pathway that can be applied for the development of novel arbovirus control strategies. Interestingly, overexpression of Dcr2 or R2d2 regulated the mRNA abundance of a variety of antimicrobial immune genes, pointing to additional functions of DCR2 and R2D2 as well as cross-talk between the siRNA pathway and other immune pathways. Accordingly, transgenic overexpression of Dcr2 or R2d2 resulted in a lesser proliferation of the midgut microbiota and increased resistance to bacterial and fungal infections.

This study shows that transgenic overexpression of siRNA pathway factors in mosquitoes mediates a broad-spectrum antiviral action against human pathogenic viruses such as dengue, Zika and Chikungunya virus, with implications for novel arbovirus control strategies; the siRNA pathway also regulates antimicrobial immune responses against bacterial and fungal infections.     

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.     

Unsuspected Dengue as a Cause of Acute Febrile Illness in Children and Adults in Western Nicaragua

BackgroundDengue is an emerging infectious disease of global significance. Suspected dengue, especially in children in Nicaragua’s heavily-urbanized capital of Managua, has been well documented, but unsuspected dengue among children and adults with undifferentitated fever has not.Conclusions/SignificanceDengue is an important and largely unrecognized cause of fever in rural western Nicaragua. Since Zika virus is transmitted by the same vector and has been associated with severe congenital infections, the population we studied is at particular risk for being devastated by the Zika epidemic that has now reached Central America.     

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.     

Seroprevalence of dengue,Zika, chikungunya and Ross River viruses across the Solomon Islands

Across the Pacific, and including in the Solomon Islands, outbreaks of arboviruses such as dengue, chikungunya, and Zika are increasing in frequency, scale and impact. Outbreaks of mosquito-borne disease have the potential to overwhelm the health systems of small island nations. This study mapped the seroprevalence of dengue, Zika, chikungunya and Ross River viruses in 5 study sites in the Solomon Islands. Serum samples from 1,021 participants were analysed by ELISA. Overall, 56% of participants were flavivirus-seropositive for dengue (28%), Zika (1%) or both flaviviruses (27%); and 53% of participants were alphavirus-seropositive for chikungunya (3%), Ross River virus (31%) or both alphaviruses (18%). Seroprevalence for both flaviviruses and alphaviruses varied by village and age of the participant. The most prevalent arboviruses in the Solomon Islands were dengue and Ross River virus. The high seroprevalence of dengue suggests that herd immunity may be a driver of dengue outbreak dynamics in the Solomon Islands. Despite being undetected prior to this survey, serology results suggest that Ross River virus transmission is endemic. There is a real need to increase the diagnostic capacities for each of the arboviruses to support effective case management and to provide timely information to inform vector control efforts and other outbreak mitigation interventions.     

Impact of the introduction of chikungunya and zika viruses on the incidence of dengue in endemic zones of Mexico

BackgroundWith the arrival of chikungunya (CHIKV) and zika (ZIKV) viruses in Mexico, there was a decrease in diagnosed dengue virus (DENV) cases. During the first years of cocirculation (2015–2017), the algorithms established by epidemiological surveillance systems and the installed capacity limited us to one diagnostic test per sample, so there was an underestimation of cases until September 2017, when a multiplex algorithm was implemented. Therefore, the objective of this study was determine the impact of the introduction of CHIKV and ZIKV on the incidence of diagnosed DENV in endemic areas of Mexico, when performing the rediagnosis, using the multiplex algorithm, in samples from the first three years of co-circulation of these arboviruses.Methodology and principal findingsFor this, 1038 samples received by the Central Laboratory of Epidemiology between 2015 and 2017 were selected for this work. Viruses were identified by multiplex RT-qPCR, and the χ² test was used to compare categorical variables. With the new multiplex algorithm, we identified 2.4 times the rate of arbovirosis as originally reported, evidencing an underestimation of the incidence of the three viruses. Even so, significantly less dengue was observed than in previous years. The high incidence rates of chikungunya and Zika coincided with periods of dengue decline. The endemic channel showed that the cases caused by DENV rose again after the circulation of CHIKV and ZIKV decreased. In addition, 23 cases of coinfection were identified, with combinations between all viruses.Conclusions and significanceThe results obtained in this study show for the first time the real impact on the detected incidence of dengue after the introduction of CHIKV and ZIKV in Mexico, the degree of underestimation of these arboviruses in the country, as well as the co-infections between these viruses, whose importance clinical and epidemiological are still unknown.     

A conceptual model for optimizing vaccine coverage to reduce vector-borne infections in the presence of antibody-dependent enhancement

Background

Many vector-borne diseases co-circulate, as the viruses from the same family are also transmitted by the same vector species. For example, Zika and dengue viruses belong to the same Flavivirus family and are primarily transmitted by a common mosquito species Aedes aegypti. Zika outbreaks have also commonly occurred in dengue-endemic areas, and co-circulation and co-infection of both viruses have been reported. As recent immunological cross-reactivity studies have confirmed that convalescent plasma following dengue infection can enhance Zika infection, and as global efforts of developing dengue and Zika vaccines are intensified, it is important to examine whether and how vaccination against one disease in a large population may affect infection dynamics of another disease due to antibody-dependent enhancement.

Methods

Through a conceptual co-infection dynamics model parametrized by reported dengue and Zika epidemic and immunological cross-reactivity characteristics, we evaluate impact of a hypothetical dengue vaccination program on Zika infection dynamics in a single season when only one particular dengue serotype is involved.

Results

We show that an appropriately designed and optimized dengue vaccination program can not only help control the dengue spread but also, counter-intuitively, reduce Zika infections. We identify optimal dengue vaccination coverages for controlling dengue and simultaneously reducing Zika infections, as well as the critical coverages exceeding which dengue vaccination will increase Zika infections.

Conclusion

This study based on a conceptual model shows the promise of an integrative vector-borne disease control strategy involving optimal vaccination programs, in regions where different viruses or different serotypes of the same virus co-circulate, and convalescent plasma following infection from one virus (serotype) can enhance infection against another virus (serotype). The conceptual model provides a first step towards well-designed regional and global vector-borne disease immunization programs.

     

Global patterns of aegyptism without arbovirus

The world’s most important mosquito vector of viruses, Aedes aegypti, is found around the world in tropical, subtropical and even some temperate locations. While climate change may limit populations of Ae. aegypti in some regions, increasing temperatures will likely expand its territory thus increasing risk of human exposure to arboviruses in places like Europe, Northern Australia and North America, among many others. Most studies of Ae. aegypti biology and virus transmission focus on locations with high endemicity or severe outbreaks of human amplified urban arboviruses, such as dengue, Zika, and chikungunya viruses, but rarely on areas at the margins of endemicity. The objective in this study is to explore previously published global patterns in the environmental suitability for Ae. aegypti and dengue virus to reveal deviations in the probability of the vector and human disease occurring. We developed a map showing one end of the gradient being higher suitability of Ae. aegypti with low suitability of dengue and the other end of the spectrum being equal and higher environmental suitability for both Ae. aegypti and dengue. The regions of the world with Ae. aegypti environmental suitability and no endemic dengue transmission exhibits a phenomenon we term ‘aegyptism without arbovirus’. We then tested what environmental and socioeconomic variables influence this deviation map revealing a significant association with human population density, suggesting that locations with lower human population density were more likely to have a higher probability of aegyptism without arbovirus. Characterizing regions of the world with established populations of Ae. aegypti but little to no autochthonous transmission of human-amplified arboviruses is an important step in understanding and achieving aegyptism without arbovirus.     

Spatial and temporal invasion dynamics of the 2014–2017 Zika and chikungunya epidemics in Colombia

Zika virus (ZIKV) and chikungunya virus (CHIKV) were recently introduced into the Americas resulting in significant disease burdens. Understanding their spatial and temporal dynamics at the subnational level is key to informing surveillance and preparedness for future epidemics. We analyzed anonymized line list data on approximately 105,000 Zika virus disease and 412,000 chikungunya fever suspected and laboratory-confirmed cases during the 2014–2017 epidemics. We first determined the week of invasion in each city. Out of 1,122, 288 cities met criteria for epidemic invasion by ZIKV and 338 cities by CHIKV. We analyzed risk factors for invasion using linear and logistic regression models. We also estimated that the geographic origin of both epidemics was located in Barranquilla, north Colombia. We assessed the spatial and temporal invasion dynamics of both viruses to analyze transmission between cities using a suite of (i) gravity models, (ii) Stouffer’s rank models, and (iii) radiation models with two types of distance metrics, geographic distance and travel time between cities. Invasion risk was best captured by a gravity model when accounting for geographic distance and intermediate levels of density dependence; Stouffer’s rank model with geographic distance performed similarly well. Although a few long-distance invasion events occurred at the beginning of the epidemics, an estimated distance power of 1.7 (95% CrI: 1.5–2.0) from the gravity models suggests that spatial spread was primarily driven by short-distance transmission. Similarities between the epidemics were highlighted by jointly fitted models, which were preferred over individual models when the transmission intensity was allowed to vary across arboviruses. However, ZIKV spread considerably faster than CHIKV.