Search

Introduction Yellow fever (YF) is primarily transmitted by Haemagogus species of mosquitoes. Under climate change, mosquitoes and the pathogens that they carry are expected to develop faster, potentially impacting the case count and duration of YF outbreaks. The aim of this study was to determine how YF virus outbreaks in Brazil may change under future climate, using ensemble simulations from regional climate models under RCP4.5 and RCP8.5 scenarios for three time periods: 2011–2040 (short-term), 2041–2070 (mid-term), and 2071–2100 (long-term). Methods A compartmental model was developed to fit the 2017/18 YF outbreak data in Brazil using least squares optimization. To explore the impact of climate change, temperature-sensitive mosquito parameters were set to change over projected time periods using polynomial equations fitted to their relationship with temperature according to the average temperature for years 2011–2040, 2041–2070, and 2071–2100 for climate change scenarios using RCP4.5 and RCP8.5, where RCP4.5/RCP8.5 corresponds to intermediate/high radiative forcing values and to moderate/higher warming trends. A sensitivity analysis was conducted to determine how the temperature-sensitive parameters impacted model results, and to determine how vaccination could play a role in reducing YF in Brazil. Results Yellow fever case projections for Brazil from the models varied when climate change scenarios were applied, including the peak clinical case incidence, cumulative clinical case incidence, time to peak incidence, and the outbreak duration. Overall, a decrease in YF cases and outbreak duration was observed. Comparing the observed incidence in 2017/18 to the projected incidence in 2070–2100, for RCP4.5, the cumulative case incidence decreased from 184 to 161, and the outbreak duration decreased from 21 to 20 weeks. For RCP8.5, the peak case incidence decreased from 184 to 147, and the outbreak duration decreased from 21 to 17 weeks. The observed decrease was primarily due to temperature increasing beyond that suitable for Haemagogus mosquito survival. Conclusions Climate change is anticipated to have an impact on mosquito-borne diseases. We found outbreaks of YF may reduce in intensity as temperatures increase in Brazil; however, temperature is not the only factor involved with disease transmission. Other factors must be explored to determine the attributable impact of climate change on mosquito-borne diseases.

Of the 3,500 species of mosquitoes worldwide, only a small portion carry and transmit the mosquito-borne diseases (MBDs) that cause approximately half a million deaths annually worldwide. The most common exotic MBDs, such as malaria and dengue, are not currently established in Canada, in part because of our relatively harsh climate; however, this situation could evolve with climate change. Mosquitoes native to Canada may become infected with new pathogens and move into new regions within Canada. In addition, new mosquito species may move into Canada from other countries, and these exotic species may bring exotic MBDs as well. With high levels of international travel, including to locations with exotic MBDs, there will be more travel-acquired cases of MBDs. With climate change, there is the potential for exotic mosquito populations to become established in Canada. There is already a small area of Canada where exotic Aedes mosquitoes have become established although, to date, there is no evidence that these carry any exotic (or already endemic) MBDs. The increased risks of spreading MBDs, or introducing exotic MBDs, will need a careful clinical and public health response. Clinicians will need to maintain a high level of awareness of current trends, to promote mosquito bite prevention strategies, and to know the laboratory tests needed for early detection and when to report laboratory results to public health. Public health efforts will need to focus on ongoing active surveillance, public and professional awareness and mosquito control. Canadians need to be aware of the risks of acquiring exotic MBDs while travelling abroad as well as the risk that they could serve as a potential route of introduction for exotic MBDs into Canada when they return home.

Background: Aedes aegypti and Ae. albopictus are mosquito vectors of more than 22 arboviruses that infect humans. Objectives: Our objective was to develop regional ecological niche models for Ae. aegypti and Ae. albopictus in the conterminous United States and Canada with current observed and simulated climate and land-use data using boosted regression trees (BRTs). Methods: We used BRTs to assess climatic suitability for Ae. albopictus and Ae. aegypti mosquitoes in Canada and the United States under current and future projected climates. Results: Models for both species were mostly influenced by minimum daily temperature and demonstrated high accuracy for predicting their geographic ranges under the current climate. The northward range expansion of suitable niches for both species was projected under future climate models. Much of the United States and parts of southern Canada are projected to be suitable for both species by 2100, with Ae. albopictus projected to expand its range north earlier this century and further north than Ae. aegypti. Discussion: Our projections suggest that the suitable ecological niche for Aedes will expand with climate change in Canada and the United States, thus increasing the risk of Aedes-transmitted arboviruses. Increased surveillance for these vectors and the pathogens they carry would be prudent. https://doi.org/10.1289/EHP5899

Introduction Zika virus (ZIKV) is primarily transmitted byAedes aegypti and Aedes albopictus mosquitoes between humans and non-human primates. Climate change may enhance virus reproduction in Aedes spp. mosquito populations, resulting in intensified ZIKV outbreaks. The study objective was to explore how an outbreak similar to the 2016 ZIKV outbreak in Brazil might unfold with projected climate change. Methods A compartmental infectious disease model that included compartments for humans and mosquitoes was developed to fit the 2016 ZIKV outbreak data from Brazil using least squares optimization. To explore the impact of climate change, published polynomial relationships between temperature and temperature-sensitive mosquito population and virus transmission parameters (mosquito mortality, development rate, and ZIKV extrinsic incubation period) were used. Projections for future outbreaks were obtained by simulating transmission with effects of projected average monthly temperatures on temperature-sensitive model parameters at each of three future time periods: 2011–2040, 2041–2070, and 2071–2100. The projected future climate was obtained from an ensemble of regional climate models (RCMs) obtained from the Co-Ordinated Regional Downscaling Experiment (CORDEX) that used Representative Concentration Pathways (RCP) with two radiative forcing values, RCP4.5 and RCP8.5. A sensitivity analysis was performed to explore the impact of temperature-dependent parameters on the model outcomes. Results Climate change scenarios impacted the model outcomes, including the peak clinical case incidence, cumulative clinical case incidence, time to peak incidence, and the duration of the ZIKV outbreak. Comparing 2070–2100 to 2016, using RCP4.5, the peak incidence was 22,030 compared to 10,473; the time to epidemic peak was 12 compared to 9 weeks, and the outbreak duration was 52 compared to 41 weeks. Comparing 2070–2100 to 2016, using RCP8.5, the peak incidence was 21,786 compared to 10,473; the time to epidemic peak was 11 compared to 9 weeks, and the outbreak duration was 50 compared to 41weeks. The increases are due to optimal climate conditions for mosquitoes, with the mean temperature reaching 28 °C in the warmest months. Under a high emission scenario (RCP8.5), mean temperatures extend above optimal for mosquito survival in the warmest months. Conclusion Outbreaks of ZIKV in locations similar to Brazil are expected to be more intense with a warming climate. As climate change impacts are becoming increasingly apparent on human health, it is important to quantify the effect and use this knowledge to inform decisions on prevention and control strategies.

In Bordetella pertussis, two serologically distinct fimbriae, FIM2 and FIM3, undergo on/off phase variation independently of each other via variation in the lengths of C stretches in the promoters for their major subunit genes, fim2 and fim3. These two promoters are also part of the BvgAS virulence regulon and therefore, if in an on configuration, are activated by phosporylated BvgA (BvgA~P) under normal growth conditions (Bvg+ mode) but not in the Bvg− mode, inducible by growth in medium containing MgSO4 or other compounds, termed modulators. In the B. pertussis Tohama I strain (FIM2+ FIM3−), the fim3 promoter is in the off state. However, a high level of transcription of the fim3 gene is observed in the Bvg− mode. In this study, we provide an explanation for this anomalous behavior by defining a Bvg-repressed promoter (BRP), located approximately 400 bp upstream of the Pfim3 transcriptional start. Although transcription of the fim3 gene in the Bvg− mode resulted in Fim3 translation, as measured by LacZ translational fusions, no accumulation of Fim3 protein was detectable. We propose that Fim3 protein resulting from translation of mRNA driven by BRP in the Bvg− mode is unstable due to a lack of the fimbrial assembly apparatus encoded by the fimBC genes, located within the fha operon, and therefore is not expressed in the Bvg− mode. IMPORTANCE In Bordetella pertussis, the promoter Pfim3-15C for the major fimbrial subunit gene fim3 is activated by the two-component system BvgAS in the Bvg+ mode but not in the Bvg− mode. However, many transcriptional profiling studies have shown that fim3 is transcribed in the Bvg− mode even when Pfim3 is in a nonpermissive state (Pfim3-13C), suggesting the presence of a reciprocally regulated element upstream of Pfim3. Here, we provide evidence that BRP is the cause of this anomalous behavior of fim3. Although BRP effects vrg-like transcription of fim3 in the Bvg− mode, it does not lead to stable production of FIM3 fimbriae, because expression of the chaperone and usher proteins FimB and FimC occurs only in the Bvg+ mode.

The two-component response regulator RisA, encoded by open reading frame BP3554 in the Bordetella pertussis Tohama I genomic sequence, is a known activator of vrg genes, a set of genes whose expression is increased under the same environmental conditions (known as modulation) that result in repression of the bvgAS virulence regulon. Here we demonstrate that RisA is phosphorylated in vivo and that RisA phosphorylation is required for activation of vrg genes. An adjacent histidine kinase gene, risS , is truncated by frameshift mutation in B. pertussis but not in Bordetella bronchiseptica or Bordetella parapertussis . Neither deletion of risS ′ or bvgAS nor phenotypic modulation with MgSO 4 affected levels of phosphorylated RisA (RisA∼P) in B. pertussis . However, RisA phosphorylation did require the histidine kinase encoded by BP3223, here named RisK (cognate histidine kinase of RisA). RisK was also required for expression of the vrg genes. This requirement could be obviated by the introduction of the phosphorylation-mimicking RisA D60E mutant, indicating that an active conformation of RisA, but not phosphorylation per se , is crucial for vrg activation. Interestingly, expression of vrg genes is still modulated by MgSO 4 in cells harboring the RisA D60E mutation, suggesting that the activated RisA senses additional signals to control vrg expression in response to environmental stimuli. IMPORTANCE In B. pertussis , the BvgAS two-component system activates the expression of virulence genes by binding of BvgA∼P to their promoters. Expression of the reciprocally regulated vrg genes requires RisA and is also repressed by the Bvg-activated BvgR. RisA is an OmpR-like response regulator, but RisA phosphorylation was not expected because the gene for its presumed, cooperonic, histidine kinase is inactivated by mutation. In this study, we demonstrate phosphorylation of RisA in vivo by a noncooperonic histidine kinase. We also show that RisA phosphorylation is necessary but not sufficient for vrg activation but, importantly, is not affected by BvgAS status. Instead, we propose that vrg expression is controlled by BvgAS through its regulation of BvgR, a cyclic di-GMP (c-di-GMP) phosphodiesterase.

Background: Chikungunya virus (CHIKV) is a reemerging pathogen transmitted by Aedes aegypti and Aedes albopictus mosquitoes. The ongoing Caribbean outbreak is of concern due to the potential for infected travelers to spread the virus to countries where vectors are present and the population is susceptible. Although there has been no autochthonous transmission of CHIKV in Canada, there is concern that both Ae. albopictus and CHIKV will become established, particularly under projected climate change. We developed risk maps for autochthonous CHIKV transmission in Canada under recent (1981–2010) and projected climate (2011–2040 and 2041–2070). Methods: The risk for CHIKV transmission was the combination of the climatic suitability for CHIKV transmission potential and the climatic suitability for the presence of Ae. albopictus; the former was assessed using a stochastic model to calculate R0 and the latter was assessed by deriving a suitability indicator (SIG) that captures a set of climatic conditions known to influence the ecology of Ae. albopictus. R0 and SIG were calculated for each grid cell in Canada south of 60°N, for each time period and for two emission scenarios, and combined to produce overall risk categories that were mapped to identify areas suitable for transmission and the duration of transmissibility. Findings: The risk for autochthonous CHIKV transmission under recent climate is very low with all of Canada classified as unsuitable or rather unsuitable for transmission. Small parts of southern coastal British Columbia become progressively suitable with short-term and long-term projected climate; the duration of potential transmission is limited to 1–2 months of the year. Interpretation: Although the current risk for autochthonous CHIKV transmission in Canada is very low, our study could be further supported by the routine surveillance of Ae. albopictus in areas identified as potentially suitable for transmission given our uncertainty on the current distribution of this species in Canada. https://doi.org/10.1289/EHP669

Zika virus (ZIKV) infection is emerging globally, currently causing outbreaks in the Caribbean, and Central and South America, and putting travellers to affected countries at risk. Model-based estimates for the basic reproduction number (R 0 ) of ZIKV in affected Caribbean and Central and South American countries, obtained from 2015 to 2016 human case surveillance data, were compared by logistic regression and Receiver-Operating Characteristic (ROC), with the prevalence of ZIKV-positive test results in Canadians who travelled to them. Estimates of R 0 for each country were a good predictor of the ZIKV test result (ROC area under the curve = 0.83) and the odds of testing positive was 11-fold greater for travellers visiting countries with estimated R 0 ≥ 2.76, compared to those visiting countries with R 0

Ross River virus (RRV) disease is the most widespread mosquito-borne disease in Australia. The disease is maintained in enzootic cycles between mosquitoes and reservoir hosts. During outbreaks and in endemic regions, RRV transmission can be sustained between vectors and reservoir hosts in zoonotic cycles with spillover to humans. Symptoms include arthritis, rash, fever and fatigue and can persist for several months. The prevalence and associated morbidity make this disease a medically and economically important mosquito-borne disease in Australia.Climate, environment, and RRV vector and reservoir host information were used to develop predictive models in four regions in NSW over a 13-year period (1991-2004). Polynomial distributed lag (PDL) models were used to explore long-term influences of up to 2 years ago that could be related to RRV activity.Each regional model consisted of a unique combination of predictors for RRV disease highlighting the differences in the disease ecology and epidemiology in New South Wales (NSW). Events up to 2 years before were found to influence RRV activity. The shorter-term associations may reflect conditions that promote virus amplification in RRV vectors whereas long-term associations may reflect RRV reservoir host breeding and herd immunity. The models indicate an association between host populations and RRV disease, lagged by 24 months, suggesting two or more generations of susceptible juveniles may be necessary for an outbreak. Model sensitivities ranged from 60.4% to 73.1%, and model specificities ranged from 57.9% to 90.7%. This was the first study to include reservoir host data into statistical RRV models; the inclusion of host parameters was found to improve model fit significantly.The research presents the novel use of a combination of climate, environment, and RRV vector and reservoir host information in statistical predictive models. The models have potential for public health decision-making.

Chikungunya virus (CHIKV) has caused several major epidemics globally over the last two decades and is quickly expanding into new areas. Although this mosquito-borne disease is self-limiting and is not associated with high mortality, it can lead to severe, chronic and disabling arthritis, thereby posing a heavy burden to healthcare systems. The two main vectors for CHIKV are Aedes aegypti and Aedes albopictus (Asian tiger mosquito); however, many other mosquito species have been described as competent CHIKV vectors in scientific literature. With climate change, globalization and unfettered urban planning affecting many areas, CHIKV poses a significant public health risk to many countries. A scoping review was conducted to collate and categorize all pertinent information gleaned from published scientific literature on a priori defined aspects of CHIKV and its competent vectors. After developing a sensitive and specific search algorithm for the research question, seven databases were searched and data was extracted from 1920 relevant articles. Results show that CHIKV research is reported predominantly in areas after major epidemics have occurred. There has been an upsurge in CHIKV publications since 2011, especially after first reports of CHIKV emergence in the Americas. A list of hosts and vectors that could potentially be involved in the sylvatic and urban transmission cycles of CHIKV has been compiled in this scoping review. In addition, a repository of CHIKV mutations associated with evolutionary fitness and adaptation has been created by compiling and characterizing these genetic variants as reported in scientific literature.

Cryptosporidium is a waterborne parasite that causes diarrheal disease in humans and in cattle. Risk factors for human illness include contact with surface water such as lakes and rivers, exposure to contaminated municipal drinking water, as well as zoonotic transmission from livestock and agriculture. The objectives of this study are twofold: 1) to describe the temporal distribution of cryptosporidiosis in Southwestern Ontario; and 2) to determine the distribution of human cryptosporidiosis, in relation to exposures such as cryptosporidium positive cattle farms, weather events, and hydrological factors. Seasonal trends in 214 bovine and 87 human cases were assessed using regression models that predicted monthly case counts in relation to observed monthly case counts. A case-crossover approach was used to evaluate acute associations between daily environmental exposures, such as weather, hydrology, the presence of Cryptosporidium positive cattle farms within the region, and the risk of human Cryptosporidium infection. Annual seasonality was found for both human cases and bovine cases with human cases peaking in mid-summer and bovine cases peaking in late winter to early spring. Bovine cases that occurred 21 days prior to human cases were associated with a three-fold increase in the odds of human case occurrence. At both 9 and 14 days prior to human case onset, the odds of a human case increased twofold per 10-degree Celsius increase in air temperature. These results provide a preliminary hypothesis for the zoonotic transmission of cryptosporidiosis from cattle to humans via the environment and suggest that the timing of environmental conditions in relation to case occurrence is biologically plausible.

Identifying geographic distribution can improve surveillance and clinical testing procedures., The water-borne pathogen Legionella pneumophila serogroup 1 (Lp1) is the most commonly reported etiologic agent of legionellosis. To examine the genetic diversity, the long-term epidemiology, and the molecular evolution of Lp1 clinical isolates, we conducted sequence-based typing on a collection of clinical isolates representing 3 decades of culture-confirmed legionellosis in Ontario, Canada. Analysis showed that the population of Lp1 in Ontario is highly diverse and combines lineages identified worldwide with local strains. Identical types were identified in sporadic and outbreak-associated strains. In the past 15 years, the incidence of some lineages distributed worldwide has tended to decrease, and local endemic clones and lineages have emerged. Comparative geographic distribution analysis suggests that some lineages are specific to eastern North America. These findings have general clinical implications for the study of Lp1 molecular evolution and for the identification of Lp1 circulating strains in North America.

Legionella species are increasingly recognized as a cause of both healthcare- and community-acquired pneumonia (so-called "Legionnaire's disease"). These pathogens are ubiquitous in the environment, but environmental factors in the occurrence of sporadic legionellosis remain poorly understood. We analyzed all legionellosis cases identified in the Greater Toronto Area of Ontario from 1978 to 2006, and evaluated seasonal and environmental patterns in legionellosis case occurrence by using both negative binomial models and case-crossover analysis. A total of 837 cases were reported during the study period. After adjusting for seasonal effects, changes in the local watershed, rather than weather, were the strongest contributors to legionellosis risk. A 3.6-fold increase (95% confidence interval (CI), 2.4-5.3) in odds of disease was identified with decreasing watershed levels approximately 4 weeks before case-occurrence. We also found a 33% increase (95% CI, 8-64%) in odds of disease with decreasing lake temperature during the same period and a 34% increase (95% CI, 14-57%) with increasing humidity 5 weeks before case-occurrence. We conclude that local watershed ecology influences the risk of legionellosis, notwithstanding the availability of advanced water treatment capacity in Toronto. Enhancement of risk might occur through direct contamination of water sources or via introduction of micronutrients or commensal organisms into residential and hospital water supplies. These observations suggest testable hypotheses for future empiric studies.

"A disease is also farther on the road to being cured when it breaks forth from concealment and manifests its power" (Seneca, ca. 4 bc-65 ad) [1]. Legionella pneumophila burst onto the medical scene ~3 decades ago as the causative pathogen in a respiratory disease outbreak among American Legion conventioneers at Philadelphia's grand Bellevue Stratford Hotel [2]. As a result of the outbreak, 182 people became sick, 29 died, the hotel went out of business, and, ultimately, clinicians were introduced to a novel, virulent pathogen. The initial identification of legionellosis in the context of a large and virulent outbreak and the subsequent recognition of case clusters associated with cooling towers, fountains, and grocery store mist machines [3] did much to cement the perception of L pneumophila as an agent of respiratory outbreaks associated with inhalation of contaminated droplets. In the nosocomial field, such outbreaks have been associated with case-fatality rates exceeding 40% [4]. However, many clinicians now recognize that legionellosis is an important cause of sporadic community-acquired pneumonia and a relatively common cause of community-acquired pneumonia requiring admission to the intensive care unit [5]. As sensitive and noninvasive diagnostic options have expanded, so has the perceived spectrum of illness associated with Legionella species. A recent article by von Baum and colleagues [6] suggested that, when individuals with ambulatory communityacquired pneumonia are tested for legionellosis by urine antigen testing, nearly 4% may receive a diagnosis of legionellosis. Understanding of the links between the physical environment and legionellosis risk has undergone a parallel evolution. Legionella species are present in surface waters and ground water [7], and pathogenic species of Legionella frequently can be isolated from home and hospital waterdistribution systems, even in the presence of chlorine (and in the absence of identified outbreaks). The finding that monochloramination of potable water supplies (which is far more effective at killing Legionella species than is chlorination) is associated with a reduction in nosocomial legionellosis outbreaks [8] suggests that exposure to this "uncommon" pathogen via drinking water may actually be common. The association among advanced age, deficient immune status, and severe legionellosis likely results from a high frequency of microaspiration and the inability to clear aspirated organisms in individuals with these characteristics. In this issue of Clinical Infectious Diseases, Neil and Berkelman [9] provide a succinct and thought-provoking summary of recent trends in legionellosis in the United States. They report that the incidence of legionellosis increased markedly in the United States from 2002 through 2005. Should we be concerned that the incidence of a virulent infectious disease

BackgroundZoonoses account for over half of all communicable diseases causing illness in humans. As there are limited resources available for the control and prevention of zoonotic diseases, a framework for their prioritization is necessary to ensure resources are directed into those of highest importance. Although zoonotic outbreaks are a significant burden of disease in North America, the systematic prioritization of zoonoses in this region has not been previously evaluated.Methodology/principal findingsThis study describes the novel use of a well-established quantitative method, conjoint analysis (CA), to identify the relative importance of 21 key characteristics of zoonotic diseases that can be used for their prioritization in Canada and the US. Relative importance weights from the CA were used to develop a point-scoring system to derive a recommended list of zoonoses for prioritization in Canada and the US. Over 1,500 participants from the general public were recruited to complete the online survey (761 from Canada and 778 from the US). Hierarchical Bayes models were fitted to the survey data to derive CA-weighted scores. Scores were applied to 62 zoonotic diseases of public health importance in Canada and the US to rank diseases in order of priority.Conclusions/significanceThis was the first study to describe a systematic and quantitative approach to the prioritization of zoonoses in North America involving public participants. We found individuals with no prior knowledge or experience in prioritizing zoonoses were capable of producing meaningful results using CA as a novel quantitative approach to prioritization. More similarities than differences were observed between countries suggesting general agreement in disease prioritization between Canadians and Americans. We demonstrate CA as a potential tool for the prioritization of zoonoses; other prioritization exercises may also consider this approach.

Background Zoonotic diseases account for over 60% of all communicable diseases causing illness in humans and 75% of recently emerging infectious diseases. As limited resources are available for the control and prevention of zoonotic diseases, it is necessary to prioritize diseases in order to direct resources into those with the greatest needs. The selection of criteria for prioritization has traditionally been on the basis of expert opinion; however, details of the methods used to identify criteria from expert opinion often are not published and a full range of criteria may not be captured by expert opinion. Methodology/Principal Findings This study used six focus groups to identify criteria for the prioritization of zoonotic diseases in Canada. Focus groups included people from the public, animal health professionals and human health professionals. A total of 59 criteria were identified for prioritizing zoonotic diseases. Human-related criteria accounted for the highest proportion of criteria identified (55%), followed by animal-related criteria (26%) then pathogen/disease-related criteria (19%). Similarities and differences were observed in the identification and scoring of criteria for disease prioritization between groups; the public groups were strongly influenced by the individual-level of disease burden, the responsibility of the scientific community in disease prioritization and the experiences of recent events while the professional groups were influenced by the societal- and population-level of disease burden and political and public pressure. Conclusions/Significance This was the first study to describe a mixed semi-quantitative and qualitative approach to deriving criteria for disease prioritization. This was also the first study to involve the opinion of the general public regarding disease prioritization. The number of criteria identified highlights the difficulty in prioritizing zoonotic diseases. The method presented in this paper has formulated a comprehensive list of criteria that can be used to inform future disease prioritization studies.