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To aid understanding of the effect of antiviral treatment on population-level influenza transmission, we used a novel pharmacokinetic–viral kinetic transmission model to test the correlation between nasal viral load and infectiousness, and to evaluate the impact that timing of treatment with the antivirals oseltamivir or baloxavir has on influenza transmission. The model was run under three candidate profiles whereby infectiousness was assumed to be proportional to viral titer on a natural-scale, log-scale, or dose–response model. Viral kinetic profiles in the presence and absence of antiviral treatment were compared for each individual (N = 1000 simulated individuals); subsequently, viral transmission mitigation was calculated. The predicted transmission mitigation was greater with earlier administration of antiviral treatment, and with baloxavir versus oseltamivir. When treatment was initiated 12–24 hours post symptom onset, the predicted transmission mitigation was 39.9–56.4% for baloxavir and 26.6–38.3% for oseltamivir depending on the infectiousness profile. When treatment was initiated 36–48 hours post symptom onset, the predicted transmission mitigation decreased to 0.8–28.3% for baloxavir and 0.8–19.9% for oseltamivir. Model estimates were compared with clinical data from the BLOCKSTONE post-exposure prophylaxis study, which indicated the log-scale model for infectiousness best fit the observed data and that baloxavir affords greater reductions in secondary case rates compared with neuraminidase inhibitors. These findings suggest a role for baloxavir and oseltamivir in reducing influenza transmission when treatment is initiated within 48 hours of symptom onset in the index patient.

This cohort study evaluates the first 22 months of implementation of the Cherokee Nation Heath Services community-based program designed to eliminate hepatitis C virus (HCV) infection., Key Points Question Can a community-based tribal hepatitis C virus (HCV) elimination program be implemented successfully in a rural setting? Findings In this cohort study, first-time HCV screening coverage increased from 20.9% to 38.2% from 3 years before to 22 months into implementation of the Cherokee Nation Health Services HCV elimination program. Identification, treatment, and cure of newly identified current HCV infections increased. Meaning In this study, implementation of a community-based HCV elimination program was associated with an improved cascade of care; this information may serve other organizations planning to implement similar programs in large rural areas., Importance In 2019, hepatitis C virus (HCV) infection contributed to more deaths in the US than 60 other notifiable infectious diseases combined. The incidence of and mortality associated with HCV infection are highest among American Indian and Alaska Native individuals. Objective To evaluate the association of the Cherokee Nation (CN) HCV elimination program with each element of the cascade of care: HCV screening, linkage to care, treatment, and cure. Design, Setting, and Participants This cohort study used data from the CN Health Services (CNHS), which serves approximately 132 000 American Indian and Alaska Native individuals residing in the 14-county CN reservation in rural northeastern Oklahoma. Data from the first 22 months of implementation (November 1, 2015, to August 31, 2017) of an HCV elimination program were compared with those from the pre–elimination program period (October 1, 2012, to October 31, 2015). The analysis included American Indian and Alaska Native individuals aged 20 to 69 years who accessed care through the CNHS between October 1, 2012, and August 31, 2017. Cure data were recorded through April 15, 2018. Exposure The CN HCV elimination program. Main Outcomes and Measures The main outcomes were the proportions of the population screened for HCV, diagnosed with current HCV infection, linked to care, treated, and cured during the initial 22 months of the elimination program period and the pre–elimination program period. Data from electronic health records and an HCV treatment database were analyzed. The cumulative incidence of HCV infection in this population was estimated using bayesian analyses. Results Among the 74 039 eligible individuals accessing care during the elimination program period, the mean (SD) age was 36.0 (13.5) years and 55.9% were women. From the pre–elimination program period to the elimination program period, first-time HCV screening coverage increased from 20.9% to 38.2%, and identification of current HCV infection and treatment in newly screened individuals increased from a mean (SD) of 170 (40) per year to 244 (4) per year and a mean of 95 (133) per year to 215 (9) per year, respectively. During the implementation period, of the 793 individuals with current HCV infection accessing the CNHS, 664 were evaluated (83.7%), 394 (59.3%) initiated treatment, and 335 (85.0%) had documented cure. In less than 2 years, the 85% 3-year goal was reached for cure (85.0%), and the goal for linkage to care was nearly reached (83.7%), whereas screening (44.1%) and treatment initiation (59.3%) required more time and resources. Conclusions and Relevance This cohort study found that after 22 months of implementation, the CNHS community-based HCV elimination program was associated with an improved cascade of care. The facilitators and lessons learned in this program may be useful to other organizations planning similar programs.

Purpose: In the wake of a nuclear detonation, individuals with acute radiation syndrome will be a significant source of morbidity and mortality. Mathematical modeling can compare response strategie...

Treating macaques with an anti-α4β7 antibody under the umbrella of combination antiretroviral therapy (cART) during early SIV infection can lead to viral remission, with viral loads maintained at < 50 SIV RNA copies/ml after removal of all treatment in a subset of animals. Depletion of CD8+ lymphocytes in controllers resulted in transient recrudescence of viremia, suggesting that the combination of cART and anti-α4β7 antibody treatment led to a state where ongoing immune responses kept the virus undetectable in the absence of treatment. A previous mathematical model of HIV infection and cART incorporates immune effector cell responses and exhibits the property of two different viral load set-points. While the lower set-point could correspond to the attainment of long-term viral remission, attaining the higher set-point may be the result of viral rebound. Here we expand that model to include possible mechanisms of action of an anti-α4β7 antibody operating in these treated animals. We show that the model can fit the longitudinal viral load data from both IgG control and anti-α4β7 antibody treated macaques, suggesting explanations for the viral control associated with cART and an anti-α4β7 antibody treatment. This effective perturbation to the virus-host interaction can also explain observations in other nonhuman primate experiments in which cART and immunotherapy have led to post-treatment control or resetting of the viral load set-point. Interestingly, because the viral kinetics in the various treated animals differed—some animals exhibited large fluctuations in viral load after cART cessation—the model suggests that anti-α4β7 treatment could act by different primary mechanisms in different animals and still lead to post-treatment viral control. This outcome is nonetheless in accordance with a model with two stable viral load set-points, in which therapy can perturb the system from one set-point to a lower one through different biological mechanisms., Author summary Some macaques treated with an anti-α4β7 monoclonal antibody along with antiretroviral therapy during the early stages of simian immunodeficiency virus infection had their viral load become undetectable (below 50 SIV RNA copies/ml) after all treatment was stopped, whereas animals not given the antibody all had their viral loads rebound to high levels. Using a mathematical model, we examined four potential ways in which the antibody could have altered the balance between viral growth and immune control to maintain an undetectable viral load. We show that a shift to controlled infection can occur through multiple biologically reasonable mechanisms of action of the anti-α4β7 antibody.

In addition to physical ailments and the possibility of viral persistence in reproductive organs, female Ebola survivors face significant stigma and associated psychological health issues. Programs to meet the varied reproductive health needs of female Ebola survivors are critical, but lack historical models. This chapter, therefore, identifies successful programs to address the needs of young adult women with other communicable diseases, namely HIV and hepatitis.

Empirical quantification of transmission dynamics for all settings is needed when evaluating interventions and control strategies., To quantify the effect of hospital and community-based transmission and control measures on Clostridium difficile infection (CDI), we constructed a transmission model within and between hospital, community, and long-term care-facility settings. By parameterizing the model from national databases and calibrating it to C. difficile prevalence and CDI incidence, we found that hospitalized patients with CDI transmit C. difficile at a rate 15 (95% CI 7.2–32) times that of asymptomatic patients. Long-term care facility residents transmit at a rate of 27% (95% CI 13%–51%) that of hospitalized patients, and persons in the community at a rate of 0.1% (95% CI 0.062%–0.2%) that of hospitalized patients. Despite lower transmission rates for asymptomatic carriers and community sources, these transmission routes have a substantial effect on hospital-onset CDI because of the larger reservoir of hospitalized carriers and persons in the community. Asymptomatic carriers and community sources should be accounted for when designing and evaluating control interventions.

Summary Background Oral pre-exposure prophylaxis (PrEP) prevents HIV infection in men who have sex with men (MSM); however, adherence is an ongoing concern. Long-acting injectable PrEP is being tested in phase 3 trials and could address challenges associated with adherence. We examined the potential effectiveness of long-acting injectable PrEP compared with oral PrEP in MSM. Methods We used an agent-based model to simulate HIV transmission in a dynamic network of 11 245 MSM in Atlanta, GA, USA. We used raw data from studies in macaque models and pharmacokinetic data from safety trials to estimate the time-varying efficacy of long-acting injectable PrEP. The effect of long-acting injectable PrEP on the cumulative number of new HIV infections over 10 years (2015–24) was compared with no PrEP and daily oral PrEP across a range of coverage levels. Sensitivity analyses were done with varying maximum efficacy and drug half-life values. Findings In the absence of PrEP, the model predicted 2374 new HIV infections (95% simulation interval [SI] 2345–2412) between 2015 and 2024. The cumulative number of new HIV infections was reduced in all scenarios in which MSM received long-acting injectable PrEP compared with oral PrEP. At a coverage level of 35%, compared with no PrEP, long-acting injectable PrEP led to a 44% reduction in new HIV infections (1044 new infections averted [95% SI 1018–1077]) versus 33% (792 infections averted [763–821]) for oral PrEP. The relative benefit of long-acting injectable PrEP was sensitive to the assumed efficacy of injections received every 8 weeks, discontinuation rates, and terminal drug half-life. Interpretation Long-acting injectable PrEP has the potential to produce larger reductions in HIV transmission in MSM than oral PrEP. However, the real-world, population-level impact of this approach will depend on uptake of this prevention method and its effectiveness, as well as retention of patients in clinical care. Funding National Institute on Drug Abuse and National Institute of Mental Health.

Background Mosquito-borne and sexually transmitted Zika virus has become widespread across Central and South America and the Caribbean. Many Zika vaccine candidates are under active development. Objective To quantify the effect of Zika vaccine prioritization of females aged 9 to 49 years, followed by males aged 9 to 49 years, on incidence of prenatal Zika infections. Design A compartmental model of Zika transmission between mosquitoes and humans was developed and calibrated to empirical estimates of country-specific mosquito density. Mosquitoes were stratified into susceptible, exposed, and infected groups; humans were stratified into susceptible, exposed, infected, recovered, and vaccinated groups. Age-specific fertility rates, Zika sexual transmission, and country-specific demographics were incorporated. Setting 34 countries and territories in the Americas with documented Zika outbreaks. Target Population Males and females aged 9 to 49 years. Intervention Age- and sex-targeted immunization using a Zika vaccine with 75% efficacy. Measurements Annual prenatal Zika infections. Results For a base-case vaccine efficacy of 75% and vaccination coverage of 90%, immunizing females aged 9 to 49 years (the World Health Organization target population) would reduce the incidence of prenatal infections by at least 94%, depending on the country-specific Zika attack rate. In regions where an outbreak is not expected for at least 10 years, vaccination of women aged 15 to 29 years is more efficient than that of women aged 30 years or older. Limitation Population-level modeling may not capture all local and neighborhood-level heterogeneity in mosquito abundance or Zika incidence. Conclusion A Zika vaccine of moderate to high efficacy may virtually eliminate prenatal infections through a combination of direct protection and transmission reduction. Efficiency of age-specific targeting of Zika vaccination depends on the timing of future outbreaks. Primary Funding Source National Institutes of Health.

Background The effectiveness of interferon-free direct-acting antivirals (DAA) in treating chronic hepatitis C virus (HCV) is limited by low screening and treatment rates, particularly among people who inject drugs (PWIDs). Methods To evaluate the levels of screening and treatment with interferon-free DAAs that are required to control HCV incidence and HCV-associated morbidity and mortality, we developed a transmission model, stratified by age and by injection drug use, and calibrated it to epidemiological data in the United States from 1992 to 2014. We quantified the impact of administration of DAAs at current and at enhanced screening and treatment rates, focusing on outcomes of HCV incidence, prevalence, compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplants, and mortality from 2015 to 2040. Results Increasing annual treatment of patients 4-fold-from the approximately 100 000 treated historically to 400 000-is predicted to prevent 526 084 (95% confidence interval, 466 615-593 347) cases of cirrhosis and 256 315 (201 589-316 114) HCV-associated deaths. By simultaneously increasing treatment capacity and increasing the number of HCV infections diagnosed, total HCV prevalence could fall to as low as 305 599 (222 955-422 110) infections by 2040. Complete elimination of HCV transmission in the United States through treatment with DAAs would require nearly universal screening of PWIDs, with an annual treatment rate of at least 30%. Conclusions Interferon-free DAAs are projected to achieve marked reductions in HCV-associated morbidity and mortality. Aggressive expansion in HCV screening and treatment, particularly among PWIDs, would be required to eliminate HCV in the United States.

Several dengue vaccines are under development, and some are expected to become available imminently. Concomitant with the anticipated release of these vaccines, vaccine allocation strategies for dengue endemic countries in Southeast Asia and Latin America are currently under development. We developed a model of dengue transmission that incorporates the age-specific distributions of dengue burden corresponding to those in Thailand and Brazil, respectively, to determine vaccine allocations that minimize the incidence of dengue hemorrhagic fever, taking into account limited availability of vaccine doses in the initial phase of production. We showed that optimal vaccine allocation strategies vary significantly with the demographic burden of dengue hemorrhagic fever. Consequently, the strategy that is optimal for one country may be sub-optimal for another country. More specifically, we showed that, during the first years following introduction of a dengue vaccine, it is optimal to target children for dengue mass vaccination in Thailand, whereas young adults should be targeted in Brazil.

The use of poor quality antimalarial medicines, including the use of non-recommended medicines for treatment such as sulfadoxine-pyrimethamine (SP) monotherapy, undermines malaria control and elimination efforts. Furthermore, the use of subtherapeutic doses of the active ingredient(s) can theoretically promote the emergence and transmission of drug resistant parasites.We developed a deterministic compartmental model to quantify the impact of antimalarial medicine quality on the transmission of SP resistance, and validated it using sensitivity analysis and a comparison with data from Kenya collected in 2006. We modelled human and mosquito population dynamics, incorporating twoThe model predicted that an increase in human malaria cases, and among these, an increase in the proportion of SP-resistant infections, resulted from an increase in poor quality SP antimalarial use, whether it was full- or half-dose SP monotherapy.Our findings suggest that an increase in poor quality antimalarial use predicts an increase in the transmission of resistance. This highlights the need for stricter control and regulation on the availability and use of poor quality antimalarial medicines, in order to offer safe and effective treatments, and work towards the eradication of malaria.

Recent Phase 2b dengue vaccine trials have demonstrated the safety of the vaccine and estimated the vaccine efficacy with further trials underway. In anticipation of vaccine roll-out, cost-effectiveness analysis of potential vaccination policies that quantify the dynamics of disease transmission are fundamental to the optimal allocation of available doses. We developed a dengue transmission and vaccination model and calculated, for a range of vaccination costs and willingness-to-pay thresholds, the level of vaccination coverage necessary to sustain herd-immunity, the price at which vaccination is cost-effective and is cost-saving, and the sensitivity of our results to parameter uncertainty. We compared two vaccine efficacy scenarios, one a more optimistic scenario and another based on the recent lower-than-expected efficacy from the latest clinical trials. We found that herd-immunity may be achieved by vaccinating 82% (95% CI 58-100%) of the population at a vaccine efficacy of 70%. At this efficacy, vaccination may be cost-effective for vaccination costs up to US$ 534 (95% CI $369-1008) per vaccinated individual and cost-saving up to $204 (95% CI $39-678). At the latest clinical trial estimates of an average of 30% vaccine efficacy, vaccination may be cost-effective and cost-saving at costs of up to $237 (95% CI $159-512) and $93 (95% CI $15-368), respectively. Our model provides an assessment of the cost-effectiveness of dengue vaccination in Brazil and incorporates the effect of herd immunity into dengue vaccination cost-effectiveness. Our results demonstrate that at the relatively low vaccine efficacy from the recent Phase 2b dengue vaccine trials, age-targeted vaccination may still be cost-effective provided the total vaccination cost is sufficiently low.

Every year in the United States more than 12,000 women are diagnosed with cervical cancer, a disease principally caused by human papillomavirus (HPV). Bivalent and quadrivalent HPV vaccines protect against 66% of HPV-associated cervical cancers, and a new nonavalent vaccine protects against an additional 15% of cervical cancers. However, vaccination policy varies across states, and migration between states interdependently dilutes state-specific vaccination policies. To quantify the economic and epidemiological impacts of switching to the nonavalent vaccine both for individual states and for the nation as a whole, we developed a model of HPV transmission and cervical cancer incidence that incorporates state-specific demographic dynamics, sexual behavior, and migratory patterns. At the national level, the nonavalent vaccine was shown to be cost-effective compared with the bivalent and quadrivalent vaccines at any coverage despite the greater per-dose cost of the new vaccine. Furthermore, the nonavalent vaccine remains cost-effective with up to an additional 40% coverage of the adolescent population, representing 80% of girls and 62% of boys. We find that expansion of coverage would have the greatest health impact in states with the lowest coverage because of the decreasing marginal returns of herd immunity. Our results show that if policies promoting nonavalent vaccine implementation and expansion of coverage are coordinated across multiple states, all states benefit both in health and in economic terms.

Chikungunya, a re-emerging arbovirus transmitted to humans by Aedes aegypti and Ae. albopictus mosquitoes, causes debilitating disease characterized by an acute febrile phase and chronic joint pain. Chikungunya has recently spread to the island of St. Martin and subsequently throughout the Americas. The disease is now affecting 42 countries and territories throughout the Americas. While chikungunya is mainly a tropical disease, the recent introduction and subsequent spread of Ae. albopictus into temperate regions has increased the threat of chikungunya outbreaks beyond the tropics. Given that there are currently no vaccines or treatments for chikungunya, vector control remains the primary measure to curtail transmission. To investigate the effectiveness of a containment strategy that combines disease surveillance, localized vector control and transmission reduction measures, we developed a model of chikungunya transmission dynamics within a large residential neighborhood, explicitly accounting for human and mosquito movement. Our findings indicate that prompt targeted vector control efforts combined with measures to reduce transmission from symptomatic cases to mosquitoes may be highly effective approaches for controlling outbreaks of chikungunya, provided that sufficient detection of chikungunya cases can be achieved.

It is anticipated that the next generation of computational epidemic models will simulate both infectious disease transmission and dynamic human behaviour change. Individual agents within a simulation will not only infect one another, but will also have situational awareness and a decision algorithm that enables them to modify their behaviour. This paper develops such a model of behavioural response, presenting a mathematical interpretation of a well-known psychological model of individual decision making, the health belief model, suitable for incorporation within an agent-based disease-transmission model. We formalize the health belief model and demonstrate its application in modelling the prevalence of facemask use observed over the course of the 2003 Hong Kong SARS epidemic, a well-documented example of behaviour change in response to a disease outbreak.

Introduction Schistosomiasis is a chronic parasitic trematode disease that affects over 240 million people worldwide. The Schistosoma lifecycle is complex, involving transmission via specific intermediate-host freshwater snails. Predictive mathematical models of Schistosoma transmission have often chosen to simplify or ignore the details of environmental human-snail interaction in their analyses. Schistosome transmission models now aim to provide better precision for policy planning of elimination of transmission. This heightens the importance of including the environmental complexity of vector-pathogen interaction in order to make more accurate projections. Methodology and principal findings We propose a nonlinear snail force of infection (FOI) that takes into account an intermediate larval stage (miracidium) and snail biology. We focused, in particular, on the effects of snail force of infection (FOI) on the impact of mass drug administration (MDA) in human communities. The proposed (modified) model was compared to a conventional model in terms of their predictions. A longitudinal dataset generated in Kenya field studies was used for model calibration and validation. For each sample community, we calibrated modified and conventional model systems, then used them to model outcomes for a range of MDA regimens. In most cases, the modified model predicted more vigorous post-MDA rebound, with faster relapse to baseline levels of infection. The effect was pronounced in higher risk communities. When compared to observed data, only the modified system was able to successfully predict persistent rebound of Schistosoma infection. Conclusion and significance The observed impact of varying location-specific snail inputs sheds light on the diverse MDA response patterns noted in operational research on schistosomiasis control, such as the recent SCORE project. Efficiency of human-to-snail transmission is likely to be much higher than predicted by standard models, which, in practice, will make local elimination by implementation of MDA alone highly unlikely, even over a multi-decade period., Author summary Infection with blood fluke Schistosoma parasites is a major cause of disease burden around the world. Control of schistosomiasis, which is transmitted through intermediate host freshwater snails, is a priority for national and global health programs working in at-risk regions of Africa, the Mideast, Asia, the Philippines, and South America. Program planning often relies on mathematical models to project the impact of different schedules of mass drug administration (MDA) of the anti-schistosomal drug, praziquantel, in these areas. In practice, though, recent projections of standard models have failed to capture the variability of MDA program impact on community levels of infection, especially in high-risk zones. In the present study, we developed a modification of the conventional modeling approach that takes more detailed account of human-to-snail transmission. Inclusion of a revised, nonlinear form for the model’s snail infection function had profound effects on long term predictions of the impact of MDA programs for Schistosoma control. In specific, our proposed snail parameters helped to explain the persistent rebound of Schistosoma prevalence in certain high risk communities. The efficiency of human-to-snail transmission is likely to be much higher than predicted in standard models, which makes local elimination by implementation of MDA, alone, highly unlikely.

Probability distributions for carbon burning, atmospheric CO2, and global average temperature are produced by time series calibration of models of utility optimization and carbon and heat balance using log-linear production functions. Population growth is used to calibrate a logistically evolving index of development that influences production efficiency. Energy production efficiency also includes a coefficient that decreases linearly with decreasing carbon intensity of energy production. This carbon intensity is a piecewise linear function of fossil carbon depletion. That function is calibrated against historical data and extrapolated by sampling a set of hypotheses about the impact on the carbon intensity of energy production of depleting fluid fossil fuel resources and increasing cumulative carbon emissions. Atmospheric carbon balance is determined by a first order differential equation with carbon use rates and cumulative carbon use as drivers. Atmospheric CO2 is a driver in a similar heat balance. Periodic corrections are included where required to make residuals between data and model results indistinguishable from independently and identically distributed normal distributions according to statistical tests on finite Fourier power spectrum amplitudes and nearest neighbor correlations. Asymptotic approach to a sustainable non-fossil energy production is followed for a global disaggregation into a tropical/developing and temperate/more-developed region. The increase in the uncertainty of global average temperature increases nearly quadratically with the increase in the temperature from the present through the next two centuries.

Background. The degree of cross-immunity between human papillomavirus (HPV) types is fundamental both to the epidemiological dynamics of HPV and to the impact of HPV vaccination. Epidemiological data on HPV infections has been repeatedly interpreted as inconsistent with cross-immunity. Methods. We reevaluate the epidemiological data using a model to determine the odds ratios of multiple to single infections expected in the presence or absence of cross-immunity. We simulate a virtual longitudinal survey to determine the effect cross-immunity has on the prevalence of multiple infections. We calibrate our model to epidemiological data and estimate the extent of type replacement following vaccination against specific HPV types. Results. We find that cross-immunity can produce odds ratios of infection comparable with epidemiological observations. We show that the sample sizes underlying existing surveys have been insufficient to identify even intense cross-immunity. We also find that the removal of HPV type 16, type 18, and types 6 and 11 would increase the prevalence of nontargeted types by 50%, 29%, and 183%, respectively. Conclusions. Cross-immunity between HPV types is consistent with epidemiological data, contrary to previous interpretations. Cross-immunity may cause significant type replacement following vaccination, and therefore should be considered in future vaccine studies and epidemiological models.

In this paper, we demonstrate how public opinion surveys can be designed to collect information pertinent to computational behavior modeling, and we present the results of a public opinion and behavior survey conducted during the 2009–2010 H1N1 influenza pandemic. The results are used to parameterize the Health Belief Model of individual health-protective decision making. Survey subjects were asked questions about their perceptions of the then-circulating influenza and attitudes towards two personal protective behaviors: vaccination and avoidance of crowds. We empirically address two important issues in applying the Health Belief Model of behavior to computational infectious disease simulation: (1) the factors dynamically influencing the states of the Health Belief Model variables and (2) the appropriateness of the Health Belief Model in describing self-protective behavior in the context of pandemic influenza.

In this article we derive a mathematical expression characterizing the tendency for Yersinia pestis, the etiologic agent of plague, to become established in an urban rat population upon introduction, and evaluate this risk for several cities. The expression gives a threshold condition for the persistence of Y. pestis transmission in terms of measurable attributes of a local urban rat population: the average flea density and the rat colony size. If the local rat and flea populations exceed this threshold, plague circulation is predicted to continue; if not, it will burn out of its own accord. This expression may be used to evaluate both the vulnerability of a specific neighborhood and the effect of pest control strategies upon that vulnerability.

Using geo-referenced case data, we present spatial and spatio-temporal cluster analyses of the early spread of the 2013–2015 chikungunya virus (CHIKV) in Dominica, an island in the Caribbean. Spatial coordinates of the locations of the first 417 reported cases observed between December 15th, 2013 and March 11th, 2014, were captured using the Global Positioning System (GPS). We observed a preponderance of female cases, which has been reported for CHIKV outbreaks in other regions. We also noted statistically significant spatial and spatio-temporal clusters in highly populated areas and observed major clusters prior to implementation of intensive vector control programs suggesting early vector control measures, and education had an impact on the spread of the CHIKV epidemic in Dominica. A dynamical identification of clusters can lead to local assessment of risk and provide opportunities for targeted control efforts for nations experiencing CHIKV outbreaks., Author Summary Chikungunya is a disease transmitted by mosquitoes. Currently, there is an epidemic of chikungunya in several islands and countries in the Americas. Despite efforts at understanding and predicting spread, there have been no studies assessing the spatio-temporal spread of chikungunya in any of the Caribbean islands, mainly due to a lack of data. Here, we present a spatio-temporal analysis of the spread of chikungunya virus in Dominica, an island in the Western Hemisphere, using geo-referenced case data. The findings in this study suggest that females are at higher risk for chikungunya virus transmission in Dominica. In addition, there is statistically significant clustering of cases in densely populated areas. Lack of data prevented additional analyses on the impact of mosquito population density, environmental factors and housing conditions on the location and timing of the clusters. This study is relevant for chikungunya control in Dominica, and other regions can use similar methods to assess chikungunya risk at the local level.

Background A. aegypti production and human density may vary considerably in dengue endemic areas. Understanding how interactions between these factors influence the risk of transmission could improve the effectiveness of the allocation of vector control resources. To evaluate the combined impacts of variation in A. aegypti production and human density we integrated field data with simulation modeling. Methodology/Principal Findings Using data from seven censuses of A. aegypti pupae (2007–2009) and from demographic surveys, we developed an agent-based transmission model of the dengue transmission cycle across houses in 16 dengue-endemic urban ‘patches’ (1–3 city blocks each) of Armenia, Colombia. Our field data showed that 92% of pupae concentrated in only 5% of houses, defined as super-producers. Average secondary infections (R0) depended on infrequent, but highly explosive transmission events. These super-spreading events occurred almost exclusively when the introduced infectious person infected mosquitoes that were produced in super-productive containers. Increased human density favored R0, and when the likelihood of human introduction of virus was incorporated into risk, a strong interaction arose between vector production and human density. Simulated intervention of super-productive containers was substantially more effective in reducing dengue risk at higher human densities. Significance/Conclusions These results show significant interactions between human population density and the natural regulatory pattern of A. aegypti in the dynamics of dengue transmission. The large epidemiological significance of super-productive containers suggests that they have the potential to influence dengue viral adaptation to mosquitoes. Human population density plays a major role in dengue transmission, due to its potential impact on human-A. aegypti contact, both within a person's home and when visiting others. The large variation in population density within typical dengue endemic cities suggests that it should be a major consideration in dengue control policy., Author Summary In the urban dengue system the life history of the mosquito vector, Aedes aegypti, transpires mainly inside and around human residences. In this study we integrated field data from an endemic city of Colombia into a simulation model to assess how natural variation in A. aegypti production and household human density influence dengue transmission. Contrary to traditional models, we show that the basic reproductive rate of dengue (Ro) is more likely to be positively correlated with human density. Moreover, the natural regulatory pattern of A. aegypti production, where a few super-productive houses dominate vector recruitment, caused a "super-spreading" pattern, whereby the large majority of viral introductions did not generate secondary infections, and Ro depended on sporadic, highly explosive transmission events. These events were dependent on the introduced infectious human infecting mosquitoes produced in super-productive vessels. When the likelihood of human introduction was incorporated into our risk indicator, a significant interaction emerged between human density and A. aegypti super production, such that removal of these containers had a much larger impact on reducing dengue in areas of higher human density. These results show that knowledge of interactions between human population density, social interactions and the natural regulatory pattern of A. aegypti can improve the design of dengue control efforts.