RESUMO
Canine Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and transmitted by insect triatomine vectors known as kissing bugs. The agent can cause cardiac damage and long-term heart disease and death in humans, dogs, and other mammals. In laboratory settings, treatment of dogs with systemic insecticides has been shown to be highly efficacious at killing triatomines that feed on treated dogs. Method We developed compartmental vector-host models of T. cruzi transmission between the triatomine and dog population accounting for the impact of seasonality and triatomine migration on disease transmission dynamics. We considered a single vector-host model without seasonality, and model with seasonality, and a spatially coupled model. We used the models to evaluate the effectiveness of the insecticide fluralaner with different durations of treatment regimens for reducing T. cruzi infection in different transmission settings. Results In low and medium transmission settings, our model showed a marginal difference between the 3-month and 6-month regimens for reducing T. cruzi infection among dogs. The difference increases in the presence of seasonality and triatomine migration from a sylvatic transmission setting. In high transmission settings, the 3-month regimen was substantially more effective in reducing T. cruzi infections in dogs than the other regimens. Our model showed that increased migration rate reduces fluralaner effectiveness in all treatment regimens, but the relative reduction in effectiveness is minimal during the first years of treatment. However, if an additional 10% or more of triatomines killed by dog treatment were eaten by dogs, treatment could increase T. cruzi infections in the dog population at least during the first year of treatment. Conclusion Our analysis shows that treating all peridomestic dogs every three to six months for at least five years could be an effective measure to reduce T. cruzi infections in dogs and triatomines in peridomestic transmission settings. However, further studies at the local scale are needed to better understand the potential impact of routine use of fluralaner treatment on increasing dogs' consumption of dead triatomines.
Assuntos
Rhodnius , Mortalidade , Doença de Chagas , Dieta , CãesRESUMO
BACKGROUND: The World Health Organization's 2020 Goals for Chagas disease include access to antiparasitic treatment and care of all infected/ill patients. Policy makers need to know the economic value of identifying and treating patients earlier. However, the economic value of earlier treatment to cure and prevent the Chagas' spread remains unknown. METHODS: We expanded our existing Chagas disease transmission model to include identification and treatment of Chagas disease patients. We linked this to a clinical and economic model that translated chronic Chagas disease cases into health and economic outcomes. We evaluated the impact and economic outcomes (costs, cost-effectiveness, cost-benefit) of identifying and treating different percentages of patients in the acute and indeterminate disease states in a 2,000-person village in Yucatan, Mexico. RESULTS: In the absence of early treatment, 50 acute and 22 new chronic cases occurred over 50 years. Identifying and treating patients in the acute stage averted 0.5-5.4 acute cases, 0.6-5.5 chronic cases, and 0.6-10.8 disability-adjusted life years (DALYs), saving $694-$7,419 and $6,976-$79,950 from the third-party payer and societal perspectives, respectively. Treating in the indeterminate stage averted 2.2-4.9 acute cases, 6.1-12.8 chronic cases, and 11.7-31.1 DALYs, saving $7,666-$21,938 from the third-party payer perspective and $90,530-$243,068 from the societal perspective. Treating patients in both stages averted ≤9 acute cases and ≤15 chronic cases. Identifying and treating patients early was always economically dominant compared to no treatment. Identifying and treating patients earlier resulted in a cumulative cost-benefit of $7,273-$224,981 at the current cost of identification and treatment. CONCLUSIONS: Even when identifying and treating as little as 5% of cases annually, treating Chagas cases in the acute and indeterminate stages reduces transmission and provides economic and health benefits. This supports the need for improved diagnostics and access to safe and effective treatment.
Assuntos
Antiprotozoários/economia , Doença de Chagas/tratamento farmacológico , Doença de Chagas/economia , Prevenção Secundária/economia , Animais , Antiprotozoários/uso terapêutico , Doença de Chagas/parasitologia , Doença de Chagas/transmissão , Análise Custo-Benefício , Humanos , México , Resultado do Tratamento , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/fisiologiaRESUMO
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.
Assuntos
Vacinação em Massa/métodos , Complicações Infecciosas na Gravidez/prevenção & controle , Infecção por Zika virus/prevenção & controle , Adolescente , Adulto , Fatores Etários , América/epidemiologia , Criança , Feminino , Humanos , Imunidade Coletiva , Incidência , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Mosquitos Vetores , Densidade Demográfica , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Porto Rico/epidemiologia , Adulto Jovem , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/transmissãoRESUMO
BACKGROUND: The 2020 Sustainable Development goals call for 100% certified interruption or control of the three main forms of Chagas disease transmission in Latin America. However, how much will achieving these goals to varying degrees control Chagas disease; what is the potential impact of missing these goals and if they are achieved, what may be left? METHODS: We developed a compartmental simulation model that represents the triatomine, human host, and non-human host populations and vector-borne, congenital, and transfusional T. cruzi transmission between them in the domestic and peridomestic settings to evaluate the impact of limiting transmission in a 2,000 person virtual village in Yucatan, Mexico. RESULTS: Interruption of domestic vectorial transmission had the largest impact on T. cruzi transmission and prevalence in all populations. Most of the gains were achieved within the first few years. Controlling vectorial transmission resulted in a 46.1-83.0% relative reduction in the number of new acute Chagas cases for a 50-100% interruption in domestic vector-host contact. Only controlling congenital transmission led to a 2.4-8.1% (30-100% interruption) relative reduction in the total number of new acute cases and reducing only transfusional transmission led to a 0.1-0.3% (30-100% reduction). Stopping all three forms of transmission resulted in 0.5 total transmission events over five years (compared to 5.0 with no interruption); interrupting all forms by 30% resulted in 3.4 events over five years per 2,000 persons. CONCLUSIONS: While reducing domestic vectorial, congenital, and transfusional transmission can successfully reduce transmission to humans (up to 82% in one year), achieving the 2020 goals would still result in 0.5 new acute cases per 2,000 over five years. Even if the goals are missed, major gains can be achieved within the first few years. Interrupting transmission should be combined with other efforts such as a vaccine or improved access to care, especially for the population of already infected individuals.
Assuntos
Doença de Chagas/epidemiologia , Doença de Chagas/transmissão , Vetores de Doenças , Trypanosoma cruzi/isolamento & purificação , Animais , Animais Domésticos/parasitologia , Humanos , México/epidemiologia , Modelos EstatísticosRESUMO
BACKGROUND: Brazil has the second highest annual number of new leprosy cases. The aim of this study is to formally compare predictions of future new case detection rate (NCDR) trends and the annual probability of NCDR falling below 10/100,000 of four different modelling approaches in four states of Brazil: Rio Grande do Norte, Amazonas, Ceará, Tocantins. METHODS: A linear mixed model, a back-calculation approach, a deterministic compartmental model and an individual-based model were used. All models were fitted to leprosy data obtained from the Brazilian national database (SINAN). First, models were fitted to the data up to 2011, and predictions were made for NCDR for 2012-2014. Second, data up to 2014 were considered and forecasts of NCDR were generated for each year from 2015 to 2040. The resulting distributions of NCDR and the probability of NCDR being below 10/100,000 of the population for each year were then compared between approaches. RESULTS: Each model performed well in model fitting and the short-term forecasting of future NCDR. Long-term forecasting of NCDR and the probability of NCDR falling below 10/100,000 differed between models. All agree that the trend of NCDR will continue to decrease in all states until 2040. Reaching a NCDR of less than 10/100,000 by 2020 was only likely in Rio Grande do Norte. Prediction until 2040 showed that the target was also achieved in Amazonas, while in Ceará and Tocantins the NCDR most likely remain (far) above 10/100,000. CONCLUSIONS: All models agree that, while incidence is likely to decline, achieving a NCDR below 10/100,000 by 2020 is unlikely in some states. Long-term prediction showed a downward trend with more variation between models, but highlights the need for further control measures to reduce the incidence of new infections if leprosy is to be eliminated.
Assuntos
Hanseníase/diagnóstico , Hanseníase/epidemiologia , Modelos Estatísticos , Brasil/epidemiologia , Previsões , Humanos , IncidênciaRESUMO
BACKGROUND: Mathematical models can help aid public health responses to Chagas disease. Models are typically developed to fulfill a particular need, and comparing outputs from different models addressing the same question can help identify the strengths and weaknesses of the models in answering particular questions, such as those for achieving the 2020 goals for Chagas disease. METHODS: Using two separately developed models (PHICOR/CIDMA model and Princeton model), we simulated dynamics for domestic transmission of Trypanosoma cruzi (T. cruzi). We compared how well the models targeted the last 9 years and last 19 years of the 1968-1998 historical seroprevalence data from Venezuela. RESULTS: Both models were able to generate the T. cruzi seroprevalence for the next time period within reason to the historical data. The PHICOR/CIDMA model estimates of the total population seroprevalence more closely followed the trends seen in the historic data, while the Princeton model estimates of the age-specific seroprevalence more closely followed historic trends when simulating over 9 years. Additionally, results from both models overestimated T. cruzi seroprevalence among younger age groups, while underestimating the seroprevalence of T. cruzi in older age groups. CONCLUSION: The PHICOR/CIDMA and Princeton models differ in level of detail and included features, yet both were able to generate the historical changes in T. cruzi seroprevalence in Venezuela over 9 and 19-year time periods. Our model comparison has demonstrated that different model structures can be useful in evaluating disease transmission dynamics and intervention strategies.
Assuntos
Doença de Chagas/epidemiologia , Doença de Chagas/transmissão , Modelos Teóricos , Doença de Chagas/prevenção & controle , Humanos , Reprodutibilidade dos Testes , Estudos Soroepidemiológicos , Trypanosoma cruzi , Venezuela/epidemiologiaRESUMO
BACKGROUND: Because of the risk for Zika virus infection in the Americas and the links between infection and microcephaly, other serious neurologic conditions, and fetal death, health ministries across the region have advised women to delay pregnancy. However, the effectiveness of this policy in reducing prenatal Zika virus infection has yet to be quantified. OBJECTIVE: To evaluate the effectiveness of pregnancy-delay policies on the incidence and prevalence of prenatal Zika virus infection. DESIGN: Vector-borne Zika virus transmission model fitted to epidemiologic data from 2015 to 2016 on Zika virus infection in Colombia. SETTING: Colombia, August 2015 to July 2017. PATIENTS: Population of Colombia, stratified by sex, age, and pregnancy status. INTERVENTION: Recommendations to delay pregnancy by 3, 6, 9, 12, or 24 months, at different levels of adherence. MEASUREMENTS: Weekly and cumulative incidence of prenatal infections and microcephaly cases. RESULTS: With 50% adherence to recommendations to delay pregnancy by 9 to 24 months, the cumulative incidence of prenatal Zika virus infections is likely to decrease by 17% to 44%, whereas recommendations to delay pregnancy by 6 or fewer months are likely to increase prenatal infections by 2% to 7%. This paradoxical exacerbation of prenatal Zika virus exposure is due to an elevated risk for pregnancies to shift toward the peak of the outbreak. LIMITATION: Sexual transmission was not explicitly accounted for in the model because of limited data but was implicitly subsumed within the overall transmission rate, which was calibrated to observed incidence. CONCLUSION: Pregnancy delays can have a substantial effect on reducing cases of microcephaly but risks exacerbating the Zika virus outbreak if the duration is not sufficient. Duration of the delay, population adherence, and the timing of initiation of the intervention must be carefully considered. PRIMARY FUNDING SOURCE: National Institutes of Health.
Assuntos
Política de Saúde , Infecção por Zika virus/prevenção & controle , Teorema de Bayes , Colômbia/epidemiologia , Anormalidades Congênitas/prevenção & controle , Feminino , Morte Fetal/prevenção & controle , Humanos , Incidência , Masculino , Microcefalia/prevenção & controle , Modelos Estatísticos , Gravidez , Complicações Infecciosas na Gravidez/virologia , Prevalência , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Fatores de Tempo , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/transmissãoRESUMO
BACKGROUND: As Zika virus continues to spread, decisions regarding resource allocations to control the outbreak underscore the need for a tool to weigh policies according to their cost and the health burden they could avert. For example, to combat the current Zika outbreak the US President requested the allocation of $1.8 billion from Congress in February 2016. METHODOLOGY/PRINCIPAL FINDINGS: Illustrated through an interactive tool, we evaluated how the number of Zika cases averted, the period during pregnancy in which Zika infection poses a risk of microcephaly, and probabilities of microcephaly and Guillain-Barré Syndrome (GBS) impact the cost at which an intervention is cost-effective. From Northeast Brazilian microcephaly incidence data, we estimated the probability of microcephaly in infants born to Zika-infected women (0.49% to 2.10%). We also estimated the probability of GBS arising from Zika infections in Brazil (0.02% to 0.06%) and Colombia (0.08%). We calculated that each microcephaly and GBS case incurs the loss of 29.95 DALYs and 1.25 DALYs per case, as well as direct medical costs for Latin America and the Caribbean of $91,102 and $28,818, respectively. We demonstrated the utility of our cost-effectiveness tool with examples evaluating funding commitments by Costa Rica and Brazil, the US presidential proposal, and the novel approach of genetically modified mosquitoes. Our analyses indicate that the commitments and the proposal are likely to be cost-effective, whereas the cost-effectiveness of genetically modified mosquitoes depends on the country of implementation. CONCLUSIONS/SIGNIFICANCE: Current estimates from our tool suggest that the health burden from microcephaly and GBS warrants substantial expenditures focused on Zika virus control. Our results justify the funding committed in Costa Rica and Brazil and many aspects of the budget outlined in the US president's proposal. As data continue to be collected, new parameter estimates can be customized in real-time within our user-friendly tool to provide updated estimates on cost-effectiveness of interventions and inform policy decisions in country-specific settings.
Assuntos
Custos de Cuidados de Saúde , Política de Saúde , Infecção por Zika virus/economia , Infecção por Zika virus/prevenção & controle , Aedes/genética , Aedes/virologia , Animais , Animais Geneticamente Modificados , Brasil/epidemiologia , Região do Caribe/epidemiologia , Efeitos Psicossociais da Doença , Análise Custo-Benefício/legislação & jurisprudência , Costa Rica/epidemiologia , Surtos de Doenças/economia , Surtos de Doenças/legislação & jurisprudência , Surtos de Doenças/prevenção & controle , Feminino , Custos de Cuidados de Saúde/legislação & jurisprudência , Humanos , Incidência , Lactente , Microcefalia/etiologia , Microcefalia/prevenção & controle , Microcefalia/virologia , Gravidez , Complicações Infecciosas na Gravidez/economia , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/virologia , Zika virus/isolamento & purificação , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/virologiaRESUMO
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.
Assuntos
Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/transmissão , Vírus Chikungunya , Controle de Doenças Transmissíveis , Controle de Mosquitos , Aedes/virologia , Algoritmos , Animais , Surtos de Doenças , Geografia , Humanos , Insetos Vetores/virologia , Avaliação de Programas e Projetos de Saúde , Características de Residência , América do Sul , VacinasRESUMO
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.
Assuntos
Febre de Chikungunya/epidemiologia , Febre de Chikungunya/transmissão , Vírus Chikungunya/fisiologia , Adulto , Febre de Chikungunya/virologia , Análise por Conglomerados , Dominica/epidemiologia , Feminino , Sistemas de Informação Geográfica , Humanos , Masculino , Pessoa de Meia-Idade , Análise Espacial , Análise Espaço-Temporal , Adulto JovemRESUMO
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.