Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-12 (of 12 Records) |
Query Trace: Undurraga EA[original query] |
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Antibiotic consumption during the coronavirus disease 2019 pandemic and emergence of carbapenemase-producing klebsiella pneumoniae lineages among inpatients in a Chilean hospital: A time-series study and phylogenomic analysis
Allel K , Peters A , Conejeros J , Martínez JRW , Spencer-Sandino M , Riquelme-Neira R , Rivas L , Rojas P , Orellana Chea C , García P , Araos R , McGovern O , Patel TS , Arias CA , Lessa FC , Undurraga EA , Munita JM . Clin Infect Dis 2023 77 S20-s28 BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) on antimicrobial use (AU) and resistance has not been well evaluated in South America. These data are critical to inform national policies and clinical care. METHODS: At a tertiary hospital in Santiago, Chile, between 2018 and 2022, subdivided into pre- (3/2018-2/2020) and post-COVID-19 onset (3/2020-2/2022), we evaluated intravenous AU and frequency of carbapenem-resistant Enterobacterales (CRE). We grouped monthly AU (defined daily doses [DDD]/1000 patient-days) into broad-spectrum β-lactams, carbapenems, and colistin and used interrupted time-series analysis to compare AU during pre- and post-pandemic onset. We studied the frequency of carbapenemase-producing (CP) CRE and performed whole-genome sequencing analyses of all carbapenem-resistant (CR) Klebsiella pneumoniae (CRKpn) isolates collected during the study period. RESULTS: Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P < .001), 50.9 to 110.1 (P < .001), and 4.1 to 13.3 (P < .001) for broad-spectrum β-lactams, carbapenems, and colistin, respectively. The frequency of CP-CRE increased from 12.8% pre-COVID-19 to 51.9% after pandemic onset (P < .001). The most frequent CRE species in both periods was CRKpn (79.5% and 76.5%, respectively). The expansion of CP-CRE harboring blaNDM was particularly noticeable, increasing from 40% (n = 4/10) before to 73.6% (n = 39/53) after pandemic onset (P < .001). Our phylogenomic analyses revealed the emergence of two distinct genomic lineages of CP-CRKpn: ST45, harboring blaNDM, and ST1161, which carried blaKPC. CONCLUSIONS: AU and the frequency of CP-CRE increased after COVID-19 onset. The increase in CP-CRKpn was driven by the emergence of novel genomic lineages. Our observations highlight the need to strengthen infection prevention and control and antimicrobial stewardship efforts. |
Evaluation of country infrastructure as an indirect measure of dog-mediated human rabies deaths
Bonaparte SC , Moodie J , Undurraga EA , Wallace RM . Front Vet Sci 2023 10 1147543 BACKGROUND: Rabies is a neglected disease, primarily due to poor detection stemming from limited surveillance and diagnostic capabilities in most countries. As a result, there is limited ability to monitor and evaluate country, regional, and global progress towards the WHO goal of eliminating human rabies deaths by 2030. There is a need for a low-cost, readily reproducible method of estimating rabies burden and elimination capacity in endemic countries. METHODS: Publicly available economic, environmental, political, social, public health, and One Health indicators were evaluated to identify variables with strong correlation to country-level rabies burden estimates. A novel index was developed to estimate infrastructural rabies elimination capacity and annual case-burden for dog-mediated rabies virus variant (DMRVV) endemic countries. FINDINGS: Five country-level indicators with superior explanatory value represent the novel "STOP-R index:" (1) literacy rate, (2) infant mortality rate, (3) electricity access, (4) political stability, and (5) presence/severity of natural hazards. Based on the STOP-R index, 40,111 (95% CI 25,854-74,344) global human rabies deaths are estimated to occur in 2022 among DMRVV-endemic countries and are projected to decrease to 32,349 (95% CI 21,110-57,019) in 2030. INTERPRETATION: The STOP-R index offers a unique means of addressing the data gap and monitoring progress towards eliminating dog-mediated human rabies deaths. Results presented here suggest that factors external to rabies programs influence the successes of rabies elimination, and it is now possible to identify countries exceeding or lagging in expected rabies control and elimination progress based on country infrastructure. |
Cost-effectiveness analysis of integrated bite case management and sustained dog vaccination for rabies control
Taylor E , Prada JM , Del Rio Vilas V , Undurraga EA , Wallace R , Horton DL . Am J Trop Med Hyg 2023 109 (1) 205-213 The successful prevention, control, and elimination of dog-mediated rabies is challenging due to insufficient resource availability and inadequate placement. An integrated dog bite case management (IBCM) system plus dog vaccination can help address these challenges. Based on data from the IBCM system in Haiti, we conducted a cost-effectiveness evaluation of a newly established IBCM system plus sustained vaccination and compared it with 1) a no bite-case management (NBCM) and 2) a non-risk-based (NRB) program, where bite victims presenting at a health clinic would receive post-exposure prophylaxis regardless of risk assessment. We also provide cost-effectiveness guidance for an ongoing IBCM system and for sub-optimal dog vaccination coverages, considering that not all cost-effective interventions are affordable. Cost-effectiveness outcomes included average cost per human death averted (USD/death averted) and per life-year gained (LYG). The analysis used a governmental perspective. Considering a sustained 5-year implementation with 70% dog vaccination coverage, IBCM had a lower average cost per death averted (IBCM: $7,528, NBCM: $7,797, NRB: $15,244) and cost per LYG (IBCM: $152, NBCM: $158, NRB: $308) than NBCM and NRB programs. As sensitivity analysis, we estimated cost-effectiveness for alternative scenarios with lower dog-vaccination coverages (30%, 55%) and lower implementation costs. Our results suggest that better health and cost-effectiveness outcomes are achieved with the continued implementation of an IBCM program ($118 per life-year saved) compared with a newly established IBCM program ($152 per life-year saved). Our results suggest that IBCM is more cost-effective than non-integrated programs to eliminate dog-mediated human rabies. |
Cost-effectiveness of the national dog rabies prevention and control program in Mexico, 1990-2015
González-Roldán JF , Undurraga EA , Meltzer MI , Atkins C , Vargas-Pino F , Gutiérrez-Cedillo V , Hernández-Pérez JR . PLoS Negl Trop Dis 2021 15 (3) e0009130 BACKGROUND: Rabies is a viral zoonosis that imposes a substantial disease and economic burden in many developing countries. Dogs are the primary source of rabies transmission; eliminating dog rabies reduces the risk of exposure in humans significantly. Through mass annual dog rabies vaccination campaigns, the national program of rabies control in Mexico progressively reduced rabies cases in dogs and humans since 1990. In 2019, the World Health Organization validated Mexico for eliminating rabies as a public health problem. Using a governmental perspective, we retrospectively assessed the economic costs, effectiveness, and cost-effectiveness of the national program of rabies control in Mexico, 1990-2015. METHODOLOGY: Combining various data sources, including administrative records, national statistics, and scientific literature, we retrospectively compared the current scenario of annual dog vaccination campaigns and post-exposure prophylaxis (PEP) with a counterfactual scenario without an annual dog vaccination campaign but including PEP. The counterfactual scenario was estimated using a mathematical model of dog rabies transmission (RabiesEcon). We performed a thorough sensitivity analysis of the main results. PRINCIPAL FINDINGS: Results suggest that in 1990 through 2015, the national dog rabies vaccination program in Mexico prevented about 13,000 human rabies deaths, at an incremental cost (MXN 2015) of $4,700 million (USD 300 million). We estimated an average cost of $360,000 (USD 23,000) per human rabies death averted, $6,500 (USD 410) per additional year-of-life, and $3,000 (USD 190) per dog rabies death averted. Results were robust to several counterfactual scenarios, including high and low rabies transmission scenarios and various assumptions about potential costs without mass dog rabies vaccination campaigns. CONCLUSIONS: Annual dog rabies vaccination campaigns have eliminated the transmission of dog-to-dog rabies and dog-mediated human rabies deaths in Mexico. According to World Health Organization standards, our results show that the national program of rabies control in Mexico has been highly cost-effective. |
Costs and effectiveness of alternative dog vaccination strategies to improve dog population coverage in rural and urban settings during a rabies outbreak
Undurraga EA , Millien MF , Allel K , Etheart MD , Cleaton J , Ross Y , Wallace RM . Vaccine 2020 38 (39) 6162-6173 Dog-rabies elimination programs have typically relied upon parenteral vaccination at central-point locations; however, dog-ownership practices, accessibility to hard-to-reach sub-populations, resource limitations, and logistics may impact a country's ability to reach the 70% coverage goal recommended by the World Organization for Animal Health (OIE) and World Health Organization (WHO). Here we report the cost-effectiveness of different dog-vaccination strategies during a dog-rabies outbreak in urban and peri-urban sections of Croix-des-Bouquets commune of the West Department, Haiti, in 2016. Three strategies, mobile static point (MSP), mobile static point with capture-vaccinate-release (MSP+CVR), and door-to-door vaccination with oral vaccination (DDV+ORV), were applied at five randomly assigned sites and assessed for free-roaming dog vaccination coverage and total population coverage. A total of 7065 dogs were vaccinated against rabies during the vaccination campaign. Overall, free-roaming dog vaccination coverage was estimated at 52% (47%-56%) for MSP, 53% (47%-60%) for DDV+ORV, and 65% (61%-69%) for MSP+CVR (differences with MSP and DDV+ORV significant at p<0.01). Total dog vaccination coverage was 33% (95% CI: 26%-43%) for MSP, 49% (95% CI: 40%-61%) for MSP+CVR and 78% (77%-80%) for DDV+ORV (differences significant at p<0.001). Overall, the least expensive campaign was MSP, with an estimated cost of about $2039 per day ($4078 total), and the most expensive was DDV+ORV with a cost of $3246 per day ($6492 total). Despite the relative high cost of an ORV bait, combining DDV and ORV was the most cost-effective strategy in our study ($1.97 per vaccinated dog), largely due to increased efficiency of the vaccinators to target less accessible dogs. Costs per vaccinated dog were $2.20 for MSP and $2.28 for MSP+CVR. We hope the results from this study will support the design and implementation of effective dog vaccination campaigns to achieve the goal of eliminating dog-mediated human rabies deaths by 2030. |
Estimating the effectiveness of vaccine programs in dog populations
Wallace RM , Undurraga EA , Gibson A , Boone J , Pieracci EG , Gamble L , Blanton JD . Epidemiol Infect 2019 147 e247 Dogs harbor numerous zoonotic pathogens, many of which are controlled through vaccination programs. The delivery of these programs can be difficult where resources are limited. We developed a dynamic model to estimate vaccination coverage and cost-per-dog vaccinated. The model considers the main factors that affect vaccination programs: dog demographics, effectiveness of strategies, efficacy of interventions and cost. The model was evaluated on data from 18 vaccination programs representing eight countries. Sensitivity analysis was performed for dog confinement and vaccination strategies. The average difference between modelled vaccination coverage and field data was 3.8% (2.3%-5.3%). Central point vaccination was the most cost-effective vaccination strategy when >88% of the dog population was confined. More active methods of vaccination, such as door-to-door or capture-vaccinate-release, achieved higher vaccination coverage in free-roaming dog populations but were more costly. This open-access tool can aid in planning more efficient vaccination campaigns in countries with limited resources. |
Evaluation of the impact of shigellosis exclusion policies in childcare settings upon detection of a shigellosis outbreak
Carias C , Undurraga EA , Hurd J , Kahn EB , Meltzer MI , Bowen A . BMC Infect Dis 2019 19 (1) 172 BACKGROUND: In the event of a shigellosis outbreak in a childcare setting, exclusion policies are typically applied to afflicted children to limit shigellosis transmission. However, there is scarce evidence of their impact. METHODS: We evaluated five exclusion policies: Children return to childcare after: i) two consecutive laboratory tests (either PCR or culture) do not detect Shigella, ii) a single negative laboratory test (PCR or culture) does not detect Shigella, iii) seven days after beginning antimicrobial treatment, iv) after being symptom-free for 24 h, or v) 14 days after symptom onset. We also included four treatments to assess the policy options: i) immediate, effective treatment; ii) effective treatment after laboratory diagnosis; iii) no treatment; iv) ineffective treatment. Relying on published data, we calculated the likelihood that a child reentering childcare would be infectious, and the number of childcare-days lost per policy. RESULTS: Requiring two consecutive negative PCR tests yielded a probability of onward transmission of < 1%, with up to 17 childcare-days lost for children receiving effective treatment, and 53 days lost for those receiving ineffective treatment. CONCLUSIONS: Of the policies analyzed, requiring negative PCR testing before returning to childcare was the most effective to reduce the risk of shigellosis transmission, with one PCR test being the most effective for the least childcare-days lost. |
Cost-effectiveness of dog rabies vaccination programs in East Africa
Borse RH , Atkins CY , Gambhir M , Undurraga EA , Blanton JD , Kahn EB , Dyer JL , Rupprecht CE , Meltzer MI . PLoS Negl Trop Dis 2018 12 (5) e0006490 BACKGROUND: Dog rabies annually causes 24,000-70,000 deaths globally. We built a spreadsheet tool, RabiesEcon, to aid public health officials to estimate the cost-effectiveness of dog rabies vaccination programs in East Africa. METHODS: RabiesEcon uses a mathematical model of dog-dog and dog-human rabies transmission to estimate dog rabies cases averted, the cost per human rabies death averted and cost per year of life gained (YLG) due to dog vaccination programs (US 2015 dollars). We used an East African human population of 1 million (approximately 2/3 living in urban setting, 1/3 rural). We considered, using data from the literature, three vaccination options; no vaccination, annual vaccination of 50% of dogs and 20% of dogs vaccinated semi-annually. We assessed 2 transmission scenarios: low (1.2 dogs infected per infectious dog) and high (1.7 dogs infected). We also examined the impact of annually vaccinating 70% of all dogs (World Health Organization recommendation for dog rabies elimination). RESULTS: Without dog vaccination, over 10 years there would a total of be approximately 44,000-65,000 rabid dogs and 2,100-2,900 human deaths. Annually vaccinating 50% of dogs results in 10-year reductions of 97% and 75% in rabid dogs (low and high transmissions scenarios, respectively), approximately 2,000-1,600 human deaths averted, and an undiscounted cost-effectiveness of $451-$385 per life saved. Semi-annual vaccination of 20% of dogs results in in 10-year reductions of 94% and 78% in rabid dogs, and approximately 2,000-1,900 human deaths averted, and cost $404-$305 per life saved. In the low transmission scenario, vaccinating either 50% or 70% of dogs eliminated dog rabies. Results were most sensitive to dog birth rate and the initial rate of dog-to-dog transmission (Ro). CONCLUSIONS: Dog rabies vaccination programs can control, and potentially eliminate, dog rabies. The frequency and coverage of vaccination programs, along with the level of dog rabies transmission, can affect the cost-effectiveness of such programs. RabiesEcon can aid both the planning and assessment of dog rabies vaccination programs. |
Tool for eliminating dog-mediated human rabies through mass dog vaccination campaigns
Undurraga EA , Blanton JD , Thumbi SM , Mwatondo A , Muturi M , Wallace RM . Emerg Infect Dis 2017 23 (12) 2114-2116 The World Health Organization and collaborating agencies have set the goal of eliminating dog-mediated human rabies by 2030. Building on experience with rabies endemic countries, we constructed a user-friendly tool to help public health officials plan the resources needed to achieve this goal through mass vaccination of dogs. |
Potential for broad-scale transmission of Ebola virus disease during the West Africa crisis: lessons for the Global Health security agenda
Undurraga EA , Carias C , Meltzer MI , Kahn EB . Infect Dis Poverty 2017 6 (1) 159 BACKGROUND: The 2014-2016 Ebola crisis in West Africa had approximately eight times as many reported deaths as the sum of all previous Ebola outbreaks. The outbreak magnitude and occurrence of multiple Ebola cases in at least seven countries beyond Liberia, Sierra Leone, and Guinea, hinted at the possibility of broad-scale transmission of Ebola. MAIN TEXT: Using a modeling tool developed by the US Centers for Disease Control and Prevention during the Ebola outbreak, we estimated the number of Ebola cases that might have occurred had the disease spread beyond the three countries in West Africa to cities in other countries at high risk for disease transmission (based on late 2014 air travel patterns). We estimated Ebola cases in three scenarios: a delayed response, a Liberia-like response, and a fast response scenario. Based on our estimates of the number of Ebola cases that could have occurred had Ebola spread to other countries beyond the West African foci, we emphasize the need for improved levels of preparedness and response to public health threats, which is the goal of the Global Health Security Agenda. Our estimates suggest that Ebola could have potentially spread widely beyond the West Africa foci, had local and international health workers and organizations not committed to a major response effort. Our results underscore the importance of rapid detection and initiation of an effective, organized response, and the challenges faced by countries with limited public health systems. Actionable lessons for strengthening local public health systems in countries at high risk of disease transmission include increasing health personnel, bolstering primary and critical healthcare facilities, developing public health infrastructure (e.g. laboratory capacity), and improving disease surveillance. With stronger local public health systems infectious disease outbreaks would still occur, but their rapid escalation would be considerably less likely, minimizing the impact of public health threats such as Ebola. CONCLUSIONS: The Ebola outbreak could have potentially spread to other countries, where limited public health surveillance and response capabilities may have resulted in additional foci. Health security requires robust local health systems that can rapidly detect and effectively respond to an infectious disease outbreak. |
Cost-effectiveness evaluation of a novel integrated bite case management program for the control of human rabies, Haiti 2014-2015
Undurraga EA , Meltzer MI , Tran CH , Atkins CY , Etheart MD , Millien MF , Adrien P , Wallace RM . Am J Trop Med Hyg 2017 96 (6) 1307-1317 Haiti has the highest burden of rabies in the Western hemisphere, with 130 estimated annual deaths. We present the cost-effectiveness evaluation of an integrated bite case management program combining community bite investigations and passive animal rabies surveillance, using a governmental perspective. The Haiti Animal Rabies Surveillance Program (HARSP) was first implemented in three communes of the West Department, Haiti. Our evaluation encompassed all individuals exposed to rabies in the study area (N = 2,289) in 2014-2015. Costs (2014 U.S. dollars) included diagnostic laboratory development, training of surveillance officers, operational costs, and postexposure prophylaxis (PEP). We used estimated deaths averted and years of life gained (YLG) from prevented rabies as health outcomes. HARSP had higher overall costs (range: $39,568-$80,290) than the no-bitecase- management (NBCM) scenario ($15,988-$26,976), partly from an increased number of bite victims receiving PEP. But HARSP had better health outcomes than NBCM, with estimated 11 additional annual averted deaths in 2014 and nine in 2015, and 654 additional YLG in 2014 and 535 in 2015. Overall, HARSP was more cost-effective (US$ per death averted) than NBCM (2014, HARSP: $2,891-$4,735, NBCM: $5,980-$8,453; 2015, HARSP: $3,534- $7,171, NBCM: $7,298-$12,284). HARSP offers an effective human rabies prevention solution for countries transitioning from reactive to preventive strategies, such as comprehensive dog vaccination. |
Elimination of dog-mediated human rabies deaths by 2030: Needs assessment and alternatives for progress based on dog vaccination
Wallace RM , Undurraga EA , Blanton JD , Cleaton J , Franka R . Front Vet Sci 2017 4 9 BACKGROUND: Rabies imposes a substantial burden to about half of the world population. The World Health Organization (WHO), World Organization for Animal Health, and the Food and Agriculture Organization have set the goal of eliminating dog-mediated human rabies deaths by 2030. This could be achieved largely by massive administration of post-exposure prophylaxis-in perpetuity-, through elimination of dog rabies, or combining both. Here, we focused on the resources needed for the elimination of dog rabies virus by 2030. MATERIALS AND METHODS: Drawing from multiple datasets, including national dog vaccination campaigns, rabies literature, and expert opinion, we developed a model considering country-specific current dog vaccination capacity to estimate the years and resources required to achieve dog rabies elimination by 2030. Resources were determined based on four factors: (a) country development status, (b) dog vaccination costs, (c) dog rabies vaccine availability, and (d) existing animal health workers. Our calculations were based on the WHO's estimate that vaccinating 70% of the dog population for seven consecutive years would eliminate rabies. FINDINGS: If dog rabies vaccine production remains at 2015 levels, we estimate that there will be a cumulative shortage of about 7.5 billion doses to meet expected demand to achieve dog rabies elimination. We estimated a present cost of $6,300 million to eliminate dog rabies in all endemic countries, equivalent to a $3,900 million gap compared to current spending. To eliminate dog rabies, the vaccination workforce may suffice if all public health veterinarians in endemic countries were to dedicate 3 months each year to dog rabies vaccination. We discuss implications of potential technology improvements, including population management, vaccine price reduction, and increases in dog-vaccinating capacities. CONCLUSION: Our results highlight the resources needed to achieve elimination of dog-mediated human rabies deaths by 2030. As exemplified by multiple successful disease elimination efforts, one size does not fit all. We suggest pragmatic and feasible options toward global dog rabies elimination by 2030, while identifying several benefits and drawbacks of specific approaches. We hope that these results help stimulate and inform a necessary discussion on global and regional strategic planning, resource mobilization, and continuous execution of rabies virus elimination. |
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