RCE/RBC-primed (n = 8) on blood viscosity and RBC rheology. A low incidence of complications was observed in the 65 RCE sessions with only seven episodes of transient grade 2 AEs. Post-apheresis Hct and FCR reached expected values with the RCE/RBC-primed method. Both the automatic and priming procedures improved RBC deformability and decreased the sickling tendency during deoxygenation. Blood rheological features improved in both RCE/RBC-primed and automatic RCE without priming conditions. The RCE/RBC-primed procedure provides blood rheological benefits, and is safe and efficient to treat, notably in young children with SCA in prophylactic programs or curatively when a SCA complication occurs.Red blood cell exchanges are frequently used to treat and prevent cerebrovascular complications in patients with sickle cell anemia (SCA). However, the low weight of young children represents serious concerns for this procedure. The Spectra Optia device can perform automatic priming using red blood cells (RBCs) (RCE/RBC-primed) which could allow RBC exchanges (RCE) to be performed in young children without hypovolemic complications, but this method requires evaluation. We prospectively analyzed the clinical safety of the RCE/RBC-primed procedure in 12 SCA low-weight children under either a chronic RCE program or emergency treatment over 65 sessions. We monitored grade 2 adverse events (AEs) such as a decrease in blood pressure, increase in heart rate, fainting sensation, or transfusion reactions and identified the critical times during the sessions in which AEs could occur. Post-apheresis hematocrit (Hct) and a fraction of cell remaining (FCR) values were compared to the expected values. We also compared the impact of automatic RCE ( Sickle cell anemia is caused by a point mutation in the seventh position of the β-globin gene leading to the production of abnormal hemoglobin called HbS. When deoxygenated, polymerization of HbS may occur, leading to mechanical distortion of red blood cells (RBC), i.e., sickling . DecreasReplacement of sickle RBCs containing HbS with healthy RBCs containing normal hemoglobin improves the outcome of patients with SCA. This replacement can be achieved by transfusions associated with manual bloodletting. However, this methodology allows a limited exchange of abnormal RBCs and may generate blood hyperviscosity, which in turn may result in vascular complications, and does not prevent iron overload . RBC excHowever, the extracorporeal volume (EV) (160–185 ml depending on the device) of the RCE circuit limits its use in low-weight children –13. Tran® device was replaced by Spectra Optia®, which was the first device relying on a completely automatic priming procedure using RBC during RCE (RCE/RBC-primed). RCE/RBC-primed could allow RCE to be performed in young children without hypovolemic complications but this method requires evaluation. The main goal of this study was to assess the feasibility and safety of RCE/RBC-primed in low-weight children with SCA. In addition, we evaluated the impact of RCE/RBC-primed on RBC rheology and blood viscosity and compared the responses to the ones obtained with RCE without RBC priming.A few years ago, the Cobe SpectraThis prospective study was conducted in accordance with the Declaration of Helsinki and approved by the Hospices Civils de Lyon ethics committee (L14-127). Twelve children with SCA were included after obtaining parental written informed consent. The inclusion criterion was a body weight < 20 kg and the exclusion criterion was hemodynamic instability with mean systolic blood pressure (sBP) < 50 mmHg.In chronic programs, RCE sessions were performed every 6 weeks. Otherwise, RCE sessions were performed when an acute SCA complication occurred. Venous access was short-term central venous access in all cases.Irregular agglutinin research was performed before RCE sessions. Transfused RBC units (RBCUs) were sickle-negative, leuco-reduced, crossmatch-compatible, and phenotypically matched for the C, E, c, e, and K (JK2 and MNS3 when possible) antigens. All the RBCUs transfused were heated to 37°C in a water bath.® software (version 7.2) calculates the volume of transfused RBCs required to reach the predictive fraction of cell remaining (pFCR) and the predictive Hct (pHct). To perform RBC priming, a supplementary compatible RBCU  was ordered and completed with ABO-compatible fresh frozen plasma to obtain a reconstituted RBCU. To prevent hemoconcentration during the critical session stage, i.e., after infusion of 185 ml of concentrated RBCs while the device has not removed significant amounts of abnormal RBCs, we primed the circuit with RBCU diluted with ABO-compatible fresh frozen plasma targeting an Hct close to the blood level of the patient, i.e., with an Hct of 28%, based on our clinical experience.Considering the low weight of the children, the TBV was calculated using the initial and simplified formulae of Glicher: TBV (ml) = weight (kg) × 75 . The num® (Terumo BCT) device circuit ranges from 141 to 185 ml (After discontinuation of the priming circuit (volume 200 ml and flow 60 ml/min), the reconstituted RBCU was removed, and the RBC-primed circuit was connected to the central venous access. Depending on the degree of filling of the infusion chamber, the EV of the RCE for the Spectra Optiao 185 ml , 15 ml/kAnticoagulation of the circuit was performed using acid citrate dextrose solution A (ACD-A), and a significant decrease in blood calcium concentration was prevented by continuous intravenous calcium infusion.The clinical tolerance of RCE using RCE/RBC-primed in low-weight children was divided into three periods: during the first 10 min of the RCE/RBC-primed sessions, corresponding to the time between the blood intake of the patient and the infusion of normal RBCs , and during two consecutive 40-min periods. Systolic BP and heart rate (HR) were monitored every 2 min during the critical time of priming reinfusion and every 10 min during the remaining session. According to the National Cancer Institute Common Terminology Criteria for Adverse Events guidelines , grade 2At the end of the RCE sessions, post-apheresis Hct was assessed to obtain actual Hct (aHct). In parallel, the post-apheresis percentage of HbS  was assessed to calculate actual FCR (aFCR). The aFCR was calculated as follows: aFCR = aHbS)/pre-apheresis HbS . We also noted the predictive FCR (pFCR) which is recorded on the device before the sessions and the final FCR (fFCR), which corresponds to the FCR recorded by the device at the end of the sessions. In parallel, we noted pre-apheresis or native Hct (nHct), predictive Hct , and final Hct .Changes in factors prone to influence hemostasis parameters were assessed, i.e., ratio of ACD-A/calcium infused and decrease in platelet blood levels .n = 8 sessions in 5 of the 12 patients followed) vs. automatic RCE  on blood viscosity and RBC rheology. The two groups of patients were assessed during RCE programs. Measurements were performed before RCE/RBC-primed, at the end of the critical time of priming reinfusion (10–15 first min) and the end of the sessions  and expressed in centipoises (cP). RBC deformability was determined at 37°C, in isotonic conditions and 3 Pa by laser diffraction analysis (ektacytometry), using the Laser-assisted Optical Rotational Cell Analyzer . In addition, ektacytometry was carried out with the oxygenscan module  to measure RBC deformability over an oxygen gradient as previously described (2) was gradually decreased from 160 to 20 mmHg (deoxygenation) and then increased to normoxic values. The diffraction pattern obtained by ektacytometry was analyzed with a camera and a computer and the elongation index (EI), which reflects RBC deformability, was also calculated. The Point of Sickling (PoS) was obtained during deoxygenation and corresponds to the pO2 at which RBC deformability decreases below 5% of the maximal deformability reached during normoxia . All measurements were standardized as recommended  after adjustment of the Hct to 40%.We also analyzed the impact of RBC-priming by comparing RCE/RBC-primed  for the device to reinfuse the volume of RBC-primed while the blood of the patient was still being removed. No significant grade 2 AEs  were observed during that time in the 65 RCE/RBC-primed sessions performed .The mean pFCR was 19 ± 4% , which cThe exchange step lasted 80 ± 11 min. All complications occurred during the last 30 min or in the first 5 min after the end of the session . SystoliWe analyzed the ability of the RCE/RBC-primed method to obtain the Hct required, and the ability to replace sufficient amounts of RBC in the blood of patients. No difference was observed between aHct, pHct, and fHct, or aFCR, pFCR, and fFCR , indicatThe ratio ACD-A/calcium infused was around 10 in most of the patients , as obseThe use of an RBCU during the priming raised the question of transient blood hyperviscosity during the priming and at the end of the sessions that could promote complications in SCA. Indeed, blood rheological parameters were investigated in 8 young low-weight children with SCA  having the RCE/RBC-primed procedure and compared to the blood rheological responses of seven older children with SCA  who were having the classical automatic RCE procedure without RBC-priming . Of noteInitial blood viscosity was lower in the RCE-RBC-primed group compared to the group having RCE without RBC priming. Blood viscosity remained unchanged in the patients having RCE/RBC-primed . HoweverThe indications of RCE during curative and prophylactic treatments of SCA are well-known . The priOur work showed that the RCE/RBC-primed method was well tolerated both during the priming and during the RCE step itself. The incidence of complications was thus very low and rapidly self-limiting. The method was safe without any risk of increasing blood viscosity during and after the sessions. Moreover, the RCE/RBC-primed method was efficient. i.e., allowed to reach the targeted post-apheresis FCR and Hct.The main problem when performing RCE in very young children is the risk of hypovolemia due to a high EV compared to a low TBV. Indeed, the study of Dedeken et al. switched from manual exchange transfusion to RCE (using the Optia Spectra system) only in children who weighed 30 kg or more, this threshold having been decided to avoid priming of the circuit . RCE tecThe performances of all types of RCE sessions, and here of RCE/RBC, had to be assessed to verify the efficiency and safety of this treatment in low-weight children. The main objective of RCE is to replace abnormal SCA-RBC with non-sickle RBC, which was evaluated by the FCR; the lower the FCR, the higher the replacement of SCA-RBC. Our results showed that the RCE/RBC-primed procedure was efficient since fFCR was similar to aFCR. Moreover, aHct was similar to both fHct and pHCt, excluding an increased risk for post-RCE stroke. Manual RBC exchange can cause a rise in Hct without improvement in blood viscosity , 28. TheOther factors need to be analyzed, in particular, hemostasis parameters as another blood product is transfused; this priming could influence the blood changes after sessions. Additional analysis of biological parameters showed a 60% decrease in platelet levels after RCE/RBC-priming. This decrease was in accordance with previous studies investigating the effects of RCE , 31. HowIn conclusion, the usage of RBC-priming in low-weight children appears necessary and safe when performing RCE. RBC-priming did not modify the performances of RCE. Altogether, these results should encourage apheresis and pediatric hematological teams to perform RCE in these low-weight children while considering many precautions. In patients with higher body weight (20–30 kg) or low body weight (15–20 kg) but low Hct, another possibility would be to perform albumin-priming. However, this therapeutic possibility has yet to be evaluated.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Hospices Civils de Lyon Ethics Commitee (L14-127). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Rotavirus vaccination was introduced into the Australian National Immunisation Program in mid-2007. We aimed to assess the impact of the rotavirus vaccination program on the burden of hospitalizations associated with all-cause acute gastroenteritis (including rotavirus gastroenteritis and non-rotavirus gastroenteritis) in the Aboriginal and non-Aboriginal population in Western Australia.We identified all hospital records, between July 2004 and June 2012, with a discharge diagnosis code for all-cause gastroenteritis. Age-specific hospitalization rates for rotavirus and non-rotavirus acute gastroenteritis before and after the introduction of the rotavirus vaccination program were compared. Interrupted time-series models were used to examine differences in the annual trends of all-cause gastroenteritis hospitalization between the two periods.Between July 2004 and June 2012, there were a total of 106,974 all-cause gastroenteritis-coded hospitalizations . Following rotavirus vaccination introduction, significant reductions in rotavirus-coded hospitalization rates were observed in all children aged <5 years . Among adults aged ≥65 years, rotavirus-coded hospitalizations were 89%  higher in the rotavirus vaccination program period. The time-series analysis suggested reductions in all-cause gastroenteritis hospitalizations in the post-vaccination period among both vaccinated and unvaccinated (age-ineligible) children, with increases observed in adults aged ≥45 years.Rotavirus vaccination has been associated with a significant decline in gastroenteritis hospitalizations among children. The increase in the elderly requires further evaluation, including assessment of the cost-benefits of rotavirus vaccination in this population. Since July 2007, rotavirus vaccination has been included in Australia’s National Immunisation Program (NIP) for all children born on or after May 1, 2007.5 The programme in Western Australia provided RV1 at ages 2 and 4 months from July 2007, and then switched to RV5 at ages 2, 4, and 6 months from July 2009. In pre- and post-licensure studies, both RV1 and RV5 have demonstrated efficacy and effectiveness against severe rotavirus gastroenteritis and all-cause gastroenteritis requiring medical attention among children in both developed and developing countries.6Globally, rotavirus is the most common cause of severe dehydrating gastroenteritis in young children.3 However, to our knowledge, the impact of the rotavirus vaccination program on the burden and epidemiology of acute gastroenteritis (including rotavirus gastroenteritis) in the Western Australian population (in both adults and children) has not been quantified. This study aimed to describe the impact of the rotavirus vaccination program on the burden of hospitalizations associated with all-cause acute gastroenteritis (including rotavirus gastroenteritis and non-rotavirus acute gastroenteritis) in the Aboriginal and non-Aboriginal population in Western Australia. Also, we conducted an interrupted time-series analysis to examine differences in the annual trends in hospital admissions for gastroenteritis between the pre-rotavirus and rotavirus vaccination periods.Our group has previously reported on the temporal trends of gastroenteritis-coded hospitalizations in Western Australian-born children aged less than 5 years, in particular noting the much greater incidence of hospitalizations among Aboriginal children.2. As of June 2016, approximately 3.9% of Western Australia’s population of 2.6 million identified as Aboriginal.7 Hospitalization data were sourced from the Western Australian Hospital Morbidity Data Collection (HMDC), which contains information on all inpatient admissions from public and private hospitals across Western Australia.8 The information includes socio-demographic details, dates of admission and separation (discharge) and discharge diagnosis codes  using the International Classification of Diseases and Related Health problems, Tenth Revision, Australian Modification (ICD-10-AM) coding system.8Western Australia is Australia’s largest state geographically, with a total land area of more than 2.5 million km9The study outcome was all-cause acute gastroenteritis-coded hospitalizations. We included all hospital records having an ICD-10-AM diagnosis code for rotavirus (A08.0) or other non-rotavirus acute gastroenteritis (A01 to A09 [excluding A08.0] and K52.9) in the principal or additional diagnosis fields. Only admission and separation dates between July 2004 and June 2012 were included. Admissions from the same person having the same diagnosis code within 14 days of a previous admission were grouped together and classified as a single episode of illness. Aboriginal status of the individual was identified using the derived Aboriginal status provided by Western Australian Data linkage branch.Using Australian Bureau of Statistics derived annual estimated resident population estimates , crude age-specific rates and crude incidence rate ratios (IRRs) for the periods prior to (July 2004–June 2007) and post (July 2007–June 2012) introduction of rotavirus onto the NIP were calculated. Estimates were calculated separately for rotavirus and non-rotavirus gastroenteritis hospitalizations for the different age groups among both Aboriginal and non-Aboriginal individuals. Exact 95% confidence intervals (CIs) and IRRs were calculated using EpiBasic .post-hoc analysis, we also modelled rotavirus-coded hospitalizations for the <12 months, 12–23 months, and 2-year age groups—the rotavirus data was too sparse to model for all age groups.Interrupted time-series models were used to evaluate changes in the all-cause gastroenteritis-coded and rotavirus-coded hospitalization rates from July 1, 2004 through November 30, 2012. For the time series, January 1, 2007 through December 31, 2007  was considered as the vaccine rollout period, July 1, 2004 to December 31, 2006 was considered as the pre-rotavirus vaccination or pre-rollout period, and January 1, 2008 onwards as the post-rotavirus vaccination or post-rollout period. Hospitalization data for rotavirus and non-rotavirus gastroenteritis were combined to assess all-cause gastroenteritis in each age group. Also, due to low absolute monthly numbers of hospitalizations in the Aboriginal population, the time-series analysis was not stratified by Aboriginal status. As 10–12 We fitted an impact model to each series using the Generalized Linear Autoregressive Moving Average (GLARMA) framework.13 We adopted negative binomial distributional assumptions when the data were over-dispersed and Poisson distributional assumptions otherwise. Equation 1 below provides the specification of the linear predictor linear predictor.Our approach is based on published recommendations and example analyses for applying segmented regression in interrupted time series.Equation 1t = 1…T withty denoting the counts of hospitalizations,t and ϕ the location and scale parameters,μtn being the exposure (population at time t),t being modelled by the exponentiated linear predictor,θk denoting the parameter for the thk regressor andβI denoting indicator variables.13 and likelihood ratio tests (LRT). Further detail on the methods is provided in the supplementary document , a pre-intervention linear trend, a change in linear trend during the rollout period , a change in linear trend during the post-rollout stage, and changes in level during the winter, spring and summer seasons. When outbreaks were known to have occurred, we introduced an additional indicator variable to model them and we included autoregressive (AR) terms in the models if the residual diagnostics suggested temporal dependence in the auto-correlation function (ACF) plots. We visually assessed residual diagnostics including residual partial-autocorrelation and autocorrelation functions to see whether modelling assumptions had been violated. We conservatively retained the full specification for all series and did not undertake model reduction. That is, we assumed that the direct effects associated with the vaccine and the indirect effects associated with herd protection, would follow the impact model. In instances where we compared models, goodness-of-fit was evaluated using Akaike Information Criterion (AIC)document .Ethical approvals were obtained from the Western Australian Department of Health Human Research Ethics Committee and the University of Western Australia. As per the request of the data custodians, individual table cell sizes of less than 5 have been suppressed.n = 200) occurred among the Aboriginal population. Rotavirus-coded hospitalization rates were highest in children aged <24 months in both population groups in the pre-rotavirus vaccination and rotavirus vaccination period  occurred among the Aboriginal population. In both the Aboriginal and non-Aboriginal population, the highest rates for these hospitalizations were associated with children aged <24 months in both time periods followed by adults aged ≥65 years . Additionally, both the 12–23 months and 2 years age group models showed seasonal effects with uplifts in the hospitalization rates during the winter and spring seasons (P ≥ 0.05), the <12 months and 2 years age group series showed statistically significant reductions in the post-rollout level relative to the pre-rollout period (P < 0.001) in the <12 months, 36%  in the 12–23 months and 43%  in the 2 years age groups  among those aged 3 years, 62%  among those aged 4 years, and 38%  in those aged 5–9 years in the post-rollout period.P-values 0.92 and 0.35, respectively). Relative to the pre-rollout rate, the model estimates for the 10–19 years age group did suggest a reduction of 29%  in the post-rollout hospitalization rate. We also note that seasonality was suggested by the data . The model for the 45–64 years age group suggested a positive trend across the whole study period with a rate ratio of 1.01  corresponding to a 1% increase in the hospitalization rate per month. However, the parameter that described the change in the pre-rollout trend in the post-rollout period had a rate ratio of 0.99 , which mostly offset the growth associated with the global trend term. Finally, among adults aged ≥65 years, the variability in this series was not as extreme as in the younger age groups and we did not find any evidence of seasonality. However, compared to the pre-rollout period, the estimate for the change in level suggested an instantaneous increase in hospitalization rates of 7%  in the post-rollout period relative to the pre-intervention period and rates have continued increase through to 2012.For the older children and adults in the 10–19, 20–44, and 45–64 years age groups, visual inspection suggested mild positive trends over the entire study period. Qualitatively, seasonality was less apparent as were level shifts between the pre-rollout and post-rollout periods. The 10–19 and the 20–44 years age groups did not show any residual temporal correlation . The magnitude of these observed declines are similar to declines observed in other countries with low child mortality wherein hospitalizations and emergency department visits due to laboratory-confirmed rotavirus gastroenteritis declined by a median of 71% following the introduction of infant rotavirus vaccination program.14–19 This suggests that many episodes of rotavirus-related hospitalizations are assigned non-specific gastroenteritis diagnostic codes.20 An Australian study has shown that only a third of all hospitalizations that tested positive for rotavirus had a rotavirus-specific diagnostic code and only 62% of all all-cause gastroenteritis-coded hospitalizations that tested positive for rotavirus had a rotavirus-specific code, with no significant differences noted in the sensitivity and specificity of the coding in the pre and post-vaccine periods.21In the period following rotavirus vaccination program introduction, significant reductions (of up to 44%) in non-rotavirus acute gastroenteritis-coded hospitalizations were also observed in children age-eligible for vaccination. Similar declines have been noted in other settings in Australia and elsewhere.16,18,22–24 A distinct increase in all-cause gastroenteritis- and rotavirus-coded hospitalization rates was observed in 2010. Rotavirus disease, like many infectious diseases, exhibits annual/seasonal cycles and studies have demonstrated an increase in the interepidemic period following the introduction of rotavirus vaccination programs.25–27 In 2010, it appears that the increase was confined to older children, suggesting this occurred in those too old to have been eligible for vaccination and who may have escaped natural infection in their earlier years due to the vaccine program.In the time-series analysis, reductions in all-cause gastroenteritis-coded hospitalizations were observed after 2007 with the introduction of the rotavirus vaccination program, even among children who were not age-eligible to be vaccinated. This suggests an indirect protective effect of the vaccination program among unvaccinated children , similar to those reported in other settings in Australia and other countries with universal rotavirus vaccination programs.Salmonella typhimurium and Salmonella enteritidis.28 Among adults aged ≥65 years, rotavirus-coded hospitalizations were 1.89 times higher in the rotavirus vaccination program period. Increase in rotavirus-related hospitalization in those aged ≥65 years following introduction of rotavirus vaccination has been observed at a national level in Australia,16,29 but this finding contrasts with studies elsewhere which have shown indirect effects among adults.30,31 As with children, reduction in rotavirus circulation in the community following vaccine introduction could have resulted in minimal exposure to the virus leading to decreased immune boosting against the virus in this population. In a randomized controlled trial, RV5 has been demonstrated to be safe and immunogenic in healthy elderly adults aged 65–80 years.32 Keeping in mind the burden of rotavirus disease in the elderly, the value and cost-benefit of rotavirus vaccination in this population needs to be evaluated.Compared to the pre-rotavirus vaccine era, all-cause gastroenteritis rates were higher in the rotavirus vaccination program period among adults. Notifications for several non-rotavirus gastroenteritis have shown a steady increase in Western Australia since 2007, especially notifications for non-typhoidal salmonella relating to foodborne outbreaks caused by The strength of this study is that it is based on a large comprehensive population-based analysis of 8 years of hospitalization data spanning pre- and post-rotavirus vaccination periods. This enabled us to analyze the age-specific burden of rotavirus-coded and non-rotavirus acute gastroenteritis-coded hospitalizations prior to and after the introduction of rotavirus vaccination. Also, because we have reliable data on Aboriginal status, we were able to analyze hospitalization rates separately for Aboriginal and non-Aboriginal children. An important limitation of our study is that we lacked information on individual immunization status and therefore, the impact of rotavirus vaccination on the vaccinated and unvaccinated cohort could not be elicited. Also, we relied on discharge diagnosis codes to identify rotavirus-coded hospitalizations and information on the temporal changes in testing practices for rotavirus in the hospital setting in Western Australia over the study period was not available. This could have underestimated the true burden of rotavirus-related hospitalization in the population.In conclusion, our findings demonstrate substantial reductions in rotavirus-specific and all-cause gastroenteritis-coded hospitalizations in children in Western Australia following the introduction of the rotavirus vaccination program. However, despite the implementation of a vaccine program with demonstrated herd immunity in children, this study did not find evidence of herd immunity among adults; our results showed a significant increase in rotavirus-coded and all-cause gastroenteritis-coded hospitalizations among adults aged ≥65 years denoting the susceptibility of this population to rotavirus. This increase in the elderly need further research to determine whether this is due to a real increase in disease with inadequate herd protection from the infant program or due to temporal changes in diagnostics practices. Continued population-level surveillance is warranted to assess the impact of rotavirus vaccination on the epidemiology of age-specific acute gastroenteritis across different age-groups and subpopulations.


Background: Robust dog vaccination coverage is the primary way to eliminate canine rabies. Haiti conducts annual canine mass vaccination campaigns, but still has the most human deaths in the Latin American and Caribbean region. We conducted an evaluation of dog vaccination methods in Haiti to determine if more intensive, data-driven vaccination methods, using smartphones for data reporting and geo-communication, could increase vaccination coverage to a level capable of disrupting rabies virus transmission.Methods: Two cities were designated into “Traditional” and “Technology-aided” vaccination areas. Traditional areas utilized historical methods of vaccination staff management, whereas Technology-aided areas used smartphone-supported spatial coordination and management of vaccination teams. Smartphones enabled real time two-way geo-communication between campaign managers and vaccinators. Campaign managers provided geographic instruction to vaccinators by assigning mapped daily vaccination boundaries displayed on phone handsets, whilst vaccinators uploaded spatial data of dogs vaccinated for review by the campaign manager to inform assignment of subsequent vaccination zones. The methods were evaluated for vaccination effort, coverage, and cost.Results: A total of 11,420 dogs were vaccinated during the 14-day campaign. The technology-aided approach achieved 80% estimated vaccination coverage as compared to 44% in traditional areas. Daily vaccination rate was higher in Traditional areas (41.7 vaccinations per team-day) compared to in technology-aided areas (26.8) but resulted in significantly lower vaccination coverages. The cost per dog vaccinated increased exponentially with the associated vaccination coverage, with a cost of $1.86 to achieve 25%, $2.51 for 50% coverage, and $3.19 for 70% coverage.Conclusions: Traditional vaccination methods failed to achieve sufficiently high vaccination coverages needed to interrupt sustained rabies virus transmission, whilst the technology-aided approach increased coverage above this critical threshold. Over successive campaigns, this difference is likely to represent the success or failure of the intervention in eliminating the rabies virus. Technology-aided vaccination should be considered in resource limited settings where rabies has not been controlled by Traditional vaccination methods. The use of technology to direct health care workers based on near-real-time spatial data from the field has myriad potential applications in other vaccination and public health initiatives. Rabies is one of the most lethal infectious diseases, and is responsible for an estimated 59,000 human deaths worldwide each year . Bites fThe Caribbean nation of Haiti has the highest poverty rate of all countries in the Americas. The resultant socio-economic instability has severely limited the capacity of health and veterinary institutions to respond to public needs . Haiti hAnnual dog vaccination campaigns in Haiti have historically immunized an estimated 100,000–300,000 dogs per year. These campaigns have traditionally consisted of vaccination teams operating temporary vaccination clinics in high-profile locations for a short time . Only restrained dogs presented by owners are vaccinated before the team moves to another location as attendance wanes. Whilst requiring minimal operational resources to implement, this method likely overlooks a sizable proportion of Haiti's free-roaming dog population.Traditional vaccination approaches rarely collect operational data to inform subsequent campaigns and make them more effective and efficient. In Haiti, the Traditional vaccination approach relies on vaccinator self-reported daily dog vaccination records. These daily totals are then aggregated for each vaccination locality, then at each department, and finally at the national level. The Traditional approach practiced in Haiti and many other low- and middle-income countries (LMICs) results in poor quality data that can take months to years before it is available for evaluation and to inform future vaccination efforts. This system does not allow for accurate data collection, timely review of data or identification of communities where vaccination rates may have failed to reach intended thresholds. In addition to questionable data quality in many LMIC vaccination campaigns, vaccination coverages are rarely assessed through field-based methods, as recommended by the World Organization for Animal Health (OIE). The combination of poor data and lack of validation of vaccination coverages can lead to chronic under-vaccination and persistent rabies endemicity.www.wvsapp.org and http://www.missionrabies.com/app) has been developed to enable efficient, scalable microplan implementation for mass dog vaccination. The system has coordinated the delivery of over one million doses of rabies vaccine to dogs in Africa and Asia  areas in the Artibonite Department of Haiti: Gonaives and Saint Marc were selected to conduct a case-control evaluation of the use of a smartphone application to implement a microplanning vaccination approach  . The VacA smartphone-web system was used to collect and aggregate vaccination data from all vaccination teams during the study. The system consists of two components: (1) a field smartphone app (WVS App) and (2) a backend website interface. The WVS app was used by vaccination teams to collect vaccination data, which were then uploaded at the completion of each vaccination day to a secure server where it could be accessed by campaign managers via the website platform for data review and campaign management [A vaccination team consisted of one veterinary technician and one assistant, with veterinary technicians having at least 2 years of experience operating rabies vaccination campaigns under the direction of the Ministère de l'Agriculture, des Ressources Naturelles et du Développement Rural (MARNDR). Vaccination teams underwent a half-day training on use of the WVS app prior to the campaign. Teams could choose between three vaccination strategies; (1) Static vaccination point (SVP) strategy where community members are encouraged to bring dogs to a fixed location where a temporary vaccination clinic has been established, (2) Door-to-door (DD) strategy where vaccination teams walked through communities inquiring if there were dogs to be vaccinated at each house, (3) Capture-vaccinate-release (CVR) strategy was available on request of the field managers using vaccination teams with additional training and equipment. Teams could switch strategies at their discretion, for example beginning DD vaccinations when attendance at SVP sites began to wane. Vaccinations were performed by trained technicians administering 1.0 mL dose of inactivated cell culture vaccine  subcutaneously. Vaccinated dogs were marked with a temporary wax crayon on the forehead and elastic gauze collar for identification in post-vaccination surveys and prevention of repeated vaccination. Each team received a unique wax color to ensure that dogs were attributed to the correct vaccination method during post-vaccination field surveys.Vaccination teams were directed by field managers; veterinary agents from the Department of Agriculture Office. These field managers were responsible for the daily management of vaccination teams, including reviewing the area vaccinated each day, managing bite exposures and ensuring vaccination data upload within the WVS App.The four study sites were assigned either Traditional (control) or Technology-aided management methodologies (case), resulting in an effective case-control study for the purpose of methodological comparison. Gonaives North and Saint-Marc North were assigned to the Traditional method and Gonaives South and Saint-Marc South were assigned to the technology-aided method; local coordinators considered these cities to have homogenous human populations and identified no concerning differences in population density, economic disparities, or dog ownership characteristics across the regions. Upon completion of the vaccination campaign, post-vaccination surveys were conducted to ensure adequate coverages had been met. In study sites assigned Traditional method, additional vaccination using a Technology-aided method was conducted if post-vaccination evaluation determined that adequate coverage had not been met. Therefore, in total three vaccination methods were evaluated in this study:1) Traditional vaccination method (Gonaives North and Saint Marc North)2) Technology-aided vaccination method (Gonaives South and Saint Marc South)3) Technology-aided after traditional vaccination method (Gonaives North and Saint Marc North)The campaign was scheduled to run for up to 14 days. Field managers at Traditional vaccination campaigns were able to stop vaccination early if they felt their respective study sites had reached adequate coverages (70%), but were told that there were funds, supplies, and staff available for the entire 14-day period.Vaccination Zones in Traditional vaccination study sites were vaccinated using campaign management methods that have been used in Haiti for over 10 years, whereby local coordinators selected vaccination sites and directed vaccination teams to community geographic landmarks  until the full 14-day vaccination campaign was completed or until post-vaccination surveys found that adequate coverages had been met.Vaccination Zones for the whole campaign area were loaded as a KML file into the web platform before the beginning of the campaign. During the Technology-aided and TA-after-traditional vaccination campaigns, central coordinators assigned Vaccination Zones to vaccination teams following a daily review of electronic records. Teams were assigned a new Vaccination Zone if the following criteria were met (i) fewer than 20 dogs per team were vaccinated in a given day, (ii) geographic visualization of vaccination points indicated homogenous vaccinations within the zone, and (iii) the teams indicated that the Vaccination Zone was complete.All communities were informed of the vaccination campaign from amplified public announcements broadcast by local coordinators while driving through the area several days before vaccination began. Additionally, 600,000 SMS messages were purchased from a major national cellular network provider and distributed to all active customers registered in the two cities at the onset  and midpoint  of the campaign. The message, in the Haitian Creole language, encouraged residents to bring all dogs to the free vaccination campaign. An evaluation of the SMS-based communication campaign has been published elsewhere . VaccinaVaccination coverage was estimated in each study site using three methods; dog sight surveys, household surveys, and human:dog ratio (HDR).Dog sight surveys were conducted in a sample of Vaccination Zones to estimate vaccination coverage in the free-roaming dog population. A two-stage cluster-sampling design was used to randomly select 33% of Vaccination Zones for post-vaccination surveys. Dog sight surveys were completed over 2 consecutive days to allow for a sight/re-sight analysis using the Lincoln-Petersen formula, which has been described in detail in other publications , 22. FreDog sight surveys were not conducted after the TA-after-traditional vaccinations. To approximate this coverage, we applied the following equation:N = Number, TAaT = Technology-aided after Traditional, and TA = Technology-AidedWhere Household surveys were conducted in regions selected for dog sight surveys to estimate vaccination coverage in the owned dog population. Vaccination coverage and human-dog-ratios (HDR) were determined from household interviews using a standardized questionnaire administered to consenting adults (>18 years). Post-vaccination household surveys were initiated in a Vaccination Zone once the field managers indicated they were complete. Owned-dog vaccination coverage was the total number of dogs reported as vaccinated during the campaign by the owner, out of the total dog population reported as owned by survey respondents. Proof of vaccination was not required.The sample size for the household interviews was calculated from an estimated human population of 291,500 in the full campaign area. It was estimated that 50% of households in Haiti own dogs . The houThe mean city-wise HDR estimate from household surveys was used to estimate the total dog population in each study site. Dog vaccination coverage was estimated using the total number of vaccinations by study site as the numerator and the HDR estimated dog population as the denominator.All manipulation and analysis of geographic information was performed using ArcMap 10.5 . At the completion of the campaign, a final dataset was aggregated from all data uploaded to the web platform and checked for accuracy against paper records. Daily and hourly vaccination rates for teams were calculated from the timestamps associated from each vaccination record using Microsoft Excel 2016 . Tests of significance for comparisons of daily mean vaccinations by area and method were calculated with an ANOVA in EpiInfo 7 . A CSV file containing the geographic coordinates of all vaccination points were spatially joined to a layer containing vaccination zone boundaries in ArcMap 10.5 to determine population-based vaccination coverage estimates.Costs were calculated for the following categories: education/awareness, transportation/logistics, vaccines/consumables, and vaccinator salary. Since vaccination study sites were not of equal sizes, the overall costs attributed to each site were adjusted based on the study site human populations and calculated as follows:Daily Campaign Cost: C(Daily Awareness)*(Site Population / Full Study Population) + C*(Site Teams / Full Study Teams) + C*N(Site Teams) + N(Vaccinated Dogs)*C(Vaccines)Costs per dog vaccinated were calculated for each study site. The cost per 1% increase in the field-based dog vaccination coverage achieved was calculated by dividing the total in-category vaccination costs by the total vaccination coverage. This is meant to approximate the program expenditures to reach a desired vaccination coverage level. Since the coverage was not assessed for TA-after-traditional vaccination, the field-based vaccination coverage was adjusted proportionally with the number of additional dogs vaccinated by this method. The average cost per dog vaccinated to achieve 70% coverage was calculated and compared across methods.2 (range 0.06–1.65 km2) and an average dog population estimate of 408 (range 257–574) based on reported human population and human-to-dog ratio of 14:1 derived from study results. On average, 29 teams (58 vaccination staff) were active each day and the entire vaccination campaign involved 422 vaccination team-days from May 20 to June 5, 2017.Vaccination Zones had a mean area of 0.33 kmn = 10,503). The door-to-door (DD) vaccination strategy accounted for 80.7%  of all vaccinations, with static vaccination point (SVP) and capture-vaccinate-release (CVR) accounting for 19.6%  and 1.2% (n = 160), respectively.A total of 11,420 dogs were vaccinated during the campaign, an overall average of 816 vaccinations per day  . On 19 oField managers declared areas assigned the Traditional vaccination method of Gonaives and Saint Marc complete after seven and three campaign days (67 and 15 team-days), respectively. The mean rate of vaccination by the Traditional method was 41.7 dogs per team-day.Teams in the technology-aided regions vaccinated for all 14 days of the campaign, representing 135 and 84 vaccination team-days in Gonaives and Saint Marc, respectively. Teams conducting the technology-aided vaccination method vaccinated 26.8 dogs per team-day .After local coordinators declared Traditional study sites complete, the Technology-aided method was implemented for the remaining campaign days to increase vaccination coverage in deficient zones (7 days in Gonaives and 11 days in Saint Marc) . The ratn = 210), followed by partially confined  with only 8.3% (n = 27) of dogs reported to be always confined at home or on a leash.Household survey teams visited 992 households and completed surveys from 682 eligible households (participation rate 68.8%) with 219 households (32.1%) reporting dog ownership. Households reported owning 325 dogs and had a human household population of 4,682, resulting in a study-derived HDR of 14:1 (95% CI 12.6–15.7). The most common confinement status was free roaming  of the 87 dog-owning households surveyed in the Traditional method area reported vaccinating their dogs in the current campaign . In TechUsing the HDR of 14:1 from the household surveys, dog population estimates yielded a mean estimated vaccination coverage of 37.2% following the Traditional vaccination method  . After tIn Traditional study sites 2-day post-vaccination field surveys sighted 383 free-roaming dogs in the 11 selected Vaccination Zones. Of these dogs, 43.9% (95% CI 39.0–48.9%) had evidence of vaccination . After tP = 0.89). Overall, the Technology-aided study sites had significantly higher population-based and free-roaming dog vaccination coverages as compared to the Traditional vaccination sites (p < 0.001). After implementing TA-after-traditional, an additional 2,128 dogs were vaccinated; a 62% increase in the number of dogs vaccinated resulting in a significantly higher dog vaccination coverage as measured by the HDR evaluation methods .When comparing between respective study sites and post-vaccination evaluation methods, the Technology-aided method resulted in higher vaccination coverages as compared to the Traditional method. In Gonaives, the Technology-aided method resulted in 1.2-fold greater overall vaccination coverage as measured by the population-based and 1.3-fold greater free-roaming dog vaccination coverage as measured by field surveys. In Saint Marc, the Technology-aided method resulted in 2.1-fold greater overall vaccination coverage as measured by the population-based and 1.8-fold greater free-roaming dog vaccination coverage as measured by field surveys. There was no difference in reported owned-dog vaccination coverage as measured by the household survey method in Saint Marc or Gonaives . Approximately $10,721 (43%) of the dog vaccination budget was spent on awareness (primarily text messages) . The remaining $14,211 was spent on consumables ($0.30 per dog), transportation ($50–$89 per team-day), and labor ($16.00 per team-day). In addition to these routine costs, the cost for data over the 2-week campaign period was $2 USD per team, or $0.14 per team-day). This cost is less than one penny per dog recorded in the App ($0.005 USD). Furthermore, the mobile phones ($80 per phone) were used for the duration of the national campaign, which recorded 330,000 dog vaccination, for a cell-phone related cost of $0.024 per dog vaccinated. The technology-related costs for this campaign totaled $0.03 USD per dog vaccinated.Among the Traditional method sites, Gonaives North averaged $1.66 per dog vaccinated by the Traditional method to achieve a coverage of 63%; this increased to $3.68 per dog vaccination after switching to TA-after-traditional, to increase the vaccination coverage to 86% . At thisAmong Technology-aided sites, Gonaives South averaged $2.19 per dog vaccinated to achieve a coverage of 82%. This site cost an average of $99 for each 1% increase in dog vaccination coverage. Saint Marc South averaged $2.42 per dog vaccinated to achieve a coverage of 76%. This site cost an average of $67 for each 1% increase in dog vaccination coverage.R2-values of 0.74 and 0.58 for Gonaives and Saint Marc, respectively. Technology-aided sites showed a polynomial association, likely reflective of the microplanning approach that was enacted. The R2 of the polynomial functions was 0.63 and 0.34 for Gonaives and Saint Marc, respectively.Overall, the association between the cost per dog vaccinated and the vaccination coverage had an exponential association, with higher coverages coming at greater relative costs . The TraThis study demonstrates that using technology-aided vaccination is feasible in a resource-limited country and can lead to significant improvement in vaccination coverage while reducing the cost per dog vaccinated to consistently achieve at least 70% vaccination coverage.Annual dog vaccination campaigns to prevent rabies have been routinely conducted in Haiti for decades, but the persistence of human rabies cases justifies the continued evaluation and improvement in the dog vaccination methods used, and their resulting coverage in the susceptible dog population. This study demonstrates that vaccination coverages achieved by Traditional vaccination methods fell far short of that needed to control rabies, a similar finding to other studies conducted in Haiti , 25. HowThe Technology-aided method evaluated in this study leveraged the improved communication afforded by smartphone-technology to direct vaccination teams on the ground based on incoming dog vaccination data. The result was a more thorough, intentional deployment of resources based on the distribution of the dog population, ultimately achieving considerably higher vaccination coverages. The daily cost per dog vaccinated using the Technology-aided method was relatively constant and fluctuated approximately every 3 days in-line with team movements . While iCompensating for areas of low coverage in Traditional vaccination study sites through follow-up Technology-aided methods was more expensive per dog vaccinated than Technology-aided methods alone. Furthermore, returning to re-vaccinate in these areas with more intensive methods can be operationally complex. Reduced efficiencies result from difficulties in identifying previously vaccinated dogs when returning to a community a second time, waning community sensitization over time, and logistical challenges to identify and redeploy vaccination teams in the community. In this study, reaching the recommended coverage level of 70% among free roaming dogs was only achieved when the Technology-aided method was implemented and suggests that planning and implementing a Technology-aided approach from the start would be more efficient than first conducting Traditional methods, followed by Technology-aided approaches to mop-up areas of low coverage.Besides overall mean vaccination coverage, the spatial distribution of vaccine across a population has been shown to be significant to the probability of achieving rabies virus elimination. Heterogeneous vaccination coverage creates an environment where rabies virus transmission can continue in pockets of low vaccination coverage, thwarting the success of the campaign in achieving rabies virus elimination , 28. TheTraditional campaigns used fewer than half of the total allotted vaccination-days, despite coordinator awareness that there were supplies, staff, and funding available for the full campaign period, an indication that coordinators thought Traditional methods yielded an acceptable coverage level. This highlights the importance of periodic post-vaccination surveys to confirm vaccine program operator decisions on when coverages have been met, as is recommended by OIE. The vaccination program in Gonaives North  achieved good coverage by the Traditional method, alone. However, this campaign still failed to achieve the goal of 70% coverage at the time in which the coordinator ended the campaign. This indicates that in certain settings, Traditional vaccination approaches may perform quite well and at a relatively low cost. In the absence of mobile technology to track vaccinations, post-vaccination surveys are required to elucidate the vaccination coverages achieved. This study shows the heterogeneity and unreliability in Traditional vaccination approaches in Haiti, which can be overcome by the implementation of mobile technologies.Robust evaluation of dog vaccination coverage is a challenge in resource-limited settings like Haiti. To start, even establishing a denominator for determining accurate coverage estimates in areas where dog population data is incorrect or missing is a difficult task . This stVaccination coverages calculated from field dog-sight surveys, which reflect coverage in the free roaming dog population and are a direct measure of the vaccination efforts, were consistently higher when using the Technology-aided vaccination method and exceeded the target vaccination coverage (70%) in both cities where it was conducted. The field survey method for estimating vaccination coverage is a direct observation method and should result in a more accurate assessment of the coverage in the dog population that is highest priority to vaccinate. The household survey method, which represents the owned dog population, was similar between the Technology-aided and Traditional vaccination methods. This could indicate that owned dogs are just as likely to be vaccinated by each method. It could also suggest that dog owners inaccurately report their participation in dog vaccination campaigns either due to confusion, concern about legal implications, or embarrassment for not vaccinating their dogs. Several studies have conducted household post-vaccination surveys in which owners are required to show proof of vaccination to verify the coverage estimates, which can eliminate this potential bias , 30. HaiFinal vaccination coverage by dog enumeration in technology-aided vaccination areas was almost twice what was seen in the Traditional areas, 80.2 and 43.9%, respectively. This difference may be due to the principle that the Traditional vaccination strategy mainly targets owned dogs which are confined at the time vaccinators present in the community and are readily able to be presented to the vaccination teams. Traditional methods bias vaccine access to well-owned, primarily confined dogs. As a result, this method may reach relatively high numbers of dogs, while still failing to achieve herd immunity in the dog populations that are primarily responsible for dog-to-dog enzootic rabies virus transmission. The technology-aided strategy involves returning to the same communities over multiple days, which we believe would allow more opportunities for vaccinating owned, free-roaming dogs that might not have been available for initial vaccination but later confined by owners until vaccination teams returned. The goal of mass dog vaccination campaigns is to establish a high level of herd immunity among the susceptible dog population, that is, dogs that can interact with each other. In this sense, vaccination coverages among the free-roaming dog population are likely the best indicator of a successful campaign, and support that the Technology-aided method described here is more effective at controlling dog-mediated rabies in Haiti.Routine recording of the GPS location of every vaccination enabled a degree of transparency and accountability impossible to achieve through paper-based records. In addition to recording data, the app allowed the teams to communicate and provide feedback to coordinators regarding the successes and challenges they faced each day. For example, teams could indicate to coordinators when they thought the Vaccination Zone was completed, or could alert coordinators of notable events, such as a dog bite incident. While this data is often communicated during Traditional methods, systematic collection enabled coordinators to access this data more readily in daily plans and to distribute this workload across multiple coordinators who have computer and internet access. Micro-planning vaccination campaigns requires that teams were able to both visualize their Vaccination Zones as well as provide this daily communication to coordinators; a process that was much more feasible with the use of a smartphone app.Integrating smartphone data collection into a dog vaccination campaign created several logistical challenges. Purchasing the phones increased the costs associated with running the campaign and required additional training time for the vaccination teams to become proficient with the software. However, the same phones were reused for the remainder of the national campaign, which logged over 300,000 dog vaccination records over the following 12 months and are intended to be used for multiple years thereby reducing this cost long term. The discounted cost of phones for large-scale dog vaccination campaigns makes the cost practically negligible compared to the logistical complexities of managing paper-based records. Vaccinators reported that it was sometimes difficult to read the screen in bright daylight and the phones had to be recharged every night for use the next day, creating additional logistical considerations for the campaign coordinators in communities where electricity is inconsistent. Many vaccinators had not navigated using web-based maps and initially found it difficult to find and stay within the boundaries of their assigned Vaccination Zone. When considering the cost to operate the Technology-aided program, the cost of Study Coordinator's time to review daily vaccination records was not considered, nor are the costs to develop or maintain the App. Mission Rabies offers the App free-to-use to collaborators, so it would be unlikely that these costs would be passed on to a low-income country's dog vaccination program. Technical experts time to review and advise on the campaign can be done remotely and could leverage international experts that volunteer their time to assist in vaccination campaigns. The cost for this component is dependent on the design of the campaign and contributions from collaborators, but in certain situations there could be added costs to the program that are not reflected in this analysis. Despite these problems experienced when introducing a new technology-driven approach to dog vaccination, the campaign experienced few problems and a low rate of vaccine data upload failure.At the conclusion of this evaluation, national coordinators from MARNDR opted to utilize the WVS App and Technology-aided micro-planning method for the remainder of the annual dog vaccination campaign in other departments of Haiti. As of February 2019, 330,000 dogs in Haiti were vaccinated using this method with periodic post-vaccination surveys finding coverage levels similar to what was reported here . For theThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This project was deemed non-research by the CDC NCEZID IACUC and IRB offices and approved by authorities at MARNDR. All animals were handled by trained MARNDR staff. Informed consent was obtained from all participants prior to beginning household surveys.This study design and protocol were developed by BM, AG, FLo, JB, EP, MN, MM, and RW. This study was performed by BM, AG, FLu, PD, KC, ME, MM, and RW. Data analysis was performed by BM, FLu, JC, and RW. This manuscript was written by BM, AG, MN, BM-F, and RW. Review and editing involved by FLo, JB, MN, BM-F, and MM. All authors contributed to the article and approved the submitted version.Merck Animal Health provided funding for distributing mobile phone SMS messages announcing the campaign.This manuscript was prepared by the authors in their personal capacity. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, the Department of Health and Human Services, or the United States Government.AG was project lead for the development of the WVS App as a part of employment for Mission Rabies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The authors found that when mitigation measures are in place, transmission within schools is limited and infection rates mirror that of the surrounding community.Severe COVID-19 in children is rare, but many schools remain closed because the transmission risk that school contact poses to adults and the wider community is unknown. Observing the heterogeneity of approaches taken among U.S. school districts, Lessler Science, abh2939, this issue p. 1092 COVID-19 rates were elevated for those connected to schools that implemented few or no mitigation measures. In-person schooling has proved contentious and difficult to study throughout the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Data from a massive online survey in the United States indicate an increased risk of COVID-19–related outcomes among respondents living with a child attending school in person. School-based mitigation measures are associated with significant reductions in risk, particularly daily symptoms screens, teacher masking, and closure of extracurricular activities. A positive association between in-person schooling and COVID-19 outcomes persists at low levels of mitigation, but when seven or more mitigation measures are reported, a significant relationship is no longer observed. Among teachers, working outside the home was associated with an increase in COVID-19–related outcomes, but this association is similar to that observed in other occupations . Although in-person schooling is associated with household COVID-19 risk, this risk can likely be controlled with properly implemented school-based mitigation measures. The role of schools in transmission—and the value of school closure—has been one of the most contentious issues of the COVID-19 pandemic. There is ongoing debate about exactly how much severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) risk is posed to individuals and communities by in-person schooling. Although there is general consensus that it should be possible to open schools safely with adequate mitigation measures, there are few data and even less agreement as to what level of mitigation is needed.Many ecological studies have shown an association between in-person schooling and the speed and extent of community SARS-CoV-2 transmission  are less susceptible to infection when exposed  through 12th-grade students are in private or charter schools—and rarely can data be linked with individual- or household-level outcomes.The COVID-19 Symptom Survey provides an opportunity to collect and analyze data on schooling behaviors and SARS-CoV-2–related outcomes from households throughout the US. This survey is administered through Facebook in partnership with Carnegie Mellon University and yields ~500,000 survey responses in the US weekly . Of 2,142,887 total respondents in the 50 US states and Washington, DC, during this period, 576,051 (26.9%) reported at least one child in pre-K through high school living in their household , living in a household with a child engaged in full-time in-person schooling is associated with a substantial increase in the odds  of reporting COVID-19–like illness , loss of taste or smell , or a positive SARS-CoV-2 test result within the previous 14 days  , loss of taste or smell , and reporting a positive test . Among those reporting part-time schooling, the association between grade and COVID-19–related outcomes is less clear . For students engaged in any form of in-person learning, the most common mitigation measure reported was student mask mandates , followed by teacher mask mandates (80%), restricted entry  (66%), and extra space between desks (63%) (see table S5 for survey-weighted rates). The distribution of mitigation measures reported was similar between those reporting full- and part-time in-person schooling, though most measures were slightly more likely to be reported in the part-time setting . BesidesOverall, respondents reporting a household child engaged in in-person school reported a mean of 6.7  mitigation measures in place at any school attended. Those reporting only children in part-time schooling reported more mitigation measures  than those reporting only children in full-time schooling . There is substantial geographic heterogeneity in the number of mitigation measures reported , an 8% decrease in the odds of loss of taste or smell , and a 7% decrease in the odds of a recent positive SARS-CoV-2 test  (table S8). Regression treating each individual mitigation measure as having an independent effect shows that daily symptom screening is clearly associated with greater risk reductions than the average measure . The confidence interval summarizing the elevation of risk overlapped with corresponding intervals that are associated with working in health care  and office work .The results presented here provide evidence that in-person schooling poses a risk to those living in the households of students but that this risk can be managed through commonly implemented school-based mitigation measures. This is consistent with findings from Sweden, where authors found risk to parents and teachers using a quasi-experimental approach  did not reveal substantial sensitivity to the levels of factors investigated, nor did examining alternative measures of individual and household COVID-19 occurrence (figs. S20 to S22), which alleviates some of these concerns. Still, more formal studies that span schools with multiple policies and approaches would enhance insights into these questions.Additionally, cross-sectional internet-based surveys have limitations and are subject to response biases. Although results are qualitatively consistent across COVID-19 outcomes , self-report has numerous limitations—for example, we cannot robustly assess asymptomatic spread. We were also unable to evaluate compliance with or investment in reported mitigation measures, and there is potential for mitigation measures to be reported inaccurately on the survey. Survey respondents may not be representative of the full US population, and although survey weights help account for nonresponse and coverage biases, weights calculated on the basis of the Facebook user base were adjusted for representativeness of the wider population on the basis of only age and gender—thus, these weights may not ensure representativeness across all covariates. However, the sample size of the survey and consistency of our findings across subanalyses allay some of these concerns, as does the assessment of non–COVID-19 outcomes (figs. S23 and S24). Further, any response biases would have to be differential based on schooling status to bias our results away from the null.The debate around in-person schooling in the US has been intense and has exacerbated differences in approach between independent school systems and individual families nationally. This lack of coordination has provided an opportunity to learn about the risks of in-person schooling and the degree to which mitigation measures may reduce risk. The results presented here provide one dimension of evidence for decision makers to consider in the context of a complex policy landscape, with many competing risks and priorities. Although online surveys have their specific limitations, the wide reach of the COVID-19 Symptom Survey has allowed us to gather data from households engaged in heterogeneous schooling activities throughout the country in a way that few other studies could. In analyzing these data, we find support for the idea that in-person schooling carries with it increased COVID-19 risk to household members, but we also find also evidence that common, low-cost mitigation measures can reduce this risk.


Trauma is ubiquitous and associated with negative effects on physical and mental health. Trauma-informed care (TIC) is a framework for mitigating these health effects and improving patients’ engagement with medical care. Despite these clinical benefits, TIC is not routinely taught in undergraduate medical education.We designed a session for first-year medical and dental students to introduce TIC principles and their application in patient care. The session focused on screening for and inquiring about trauma and responding to disclosures of trauma. Using live patient interviews, small-group discussions, and case-based role-plays, the session offered expert instruction and hands-on practice. Students completed pre- and postsession surveys and a 5-month follow-up survey. Students reported their comfort with screening for trauma and responding to disclosures of trauma before and after the session and at 5 months following the session.Of the 164 student participants, 76% completed surveys during the session, and 50% completed the follow-up survey. More than one-third (34%) of respondents reported having received at least one disclosure of trauma from a patient within the first 5 months of medical school. Students’ comfort with screening for trauma increased from 30% to 56%, and their comfort with responding to disclosure of trauma increased from 35% to 55%. These improvements persisted on reevaluation at 5 months.We present a model for teaching trauma-informed communication skills to first-year medical and dental students. The intervention significantly increased students’ comfort level and self-reported clinical skills, and benefits persisted at 5 months. A review of 26 World Health Organization World Mental Health Surveys conducted in 24 countries of various income levels found that roughly 70% of respondents had experienced at least one traumatic event in their lifetime.3 A US study found almost 90% of adults reported at least one traumatic event in their lifetime as defined by the Diagnostic and Statistical Manual of Mental Disorders-5.4Trauma is defined by the Substance Abuse and Mental Health Services Administration (SAMHSA) as “an event, series of events, or set of circumstances that is experienced by an individual as physically or emotionally harmful or life-threatening and that has lasting adverse effects on the individual's functioning and mental, physical, social, emotional, or spiritual well-being.”5 Trauma can lead to the development of posttraumatic stress disorder, which has a lifetime prevalence of 6% for men and 13% for women.4 Trauma can overwhelm coping mechanisms, elevate or exacerbate stress, and alter health-seeking behaviors.6 Specific traumas that occur in childhood, known as adverse childhood experiences, exhibit a dose-response relationship with negative mental and physical health outcomes in adulthood.7 For example, adults with the highest levels of childhood trauma were found to be 12 times more likely to attempt suicide and twice as likely to suffer from cardiovascular disease.7 Exposure to trauma has been linked to higher rates of substance use, depression, anxiety, chronic pain, and cancer.8A traumatic event may cause acute physical injuries with associated sequelae and poor long-term mental and physical health outcomes.1 TIC focuses on six key principles as defined by SAMHSA: safety ; trustworthiness and transparency (making decisions with transparency to build and maintain trust); peer support ; collaboration and mutuality ; empowerment, voice, and choice ; and cultural, historical, and gender issues .1 Given their professional values and mission, health care providers and institutions must avoid adding to the trauma burden of their patients, providers, and trainees. They can advance this goal by adopting a universal, systematic, trauma-informed approach.9Trauma-informed care (TIC) provides a framework for addressing and mitigating these health effects. TIC encourages health care providers, institutions, and systems to realize the impact of trauma; recognize the signs and symptoms of trauma; respond by integrating knowledge about trauma into policies, procedures, and practice; and seek to avoid retraumatization.9 including primary care,10 psychiatry,11 pediatrics,12 and dentistry.13 Within UME, trauma-informed medical education (TIME) has been proposed as a way to integrate trauma-informed concepts  in a trauma-informed manner .14 For example, TIME advocates introducing topics that some students might find distressing, such as intimate partner violence (IPV) or taking a sexual history , in a learning environment that applies the principles of TIC , such as offering peer support for students after a session with distressing material. TIME aims to increase the trauma competency of medical school graduates and improve learner engagement through trauma-informed learning environments.14In recent years, health care organizations have begun to incorporate TIC into clinical settings,15 Given the ubiquity of trauma, students encounter traumatic disclosures early on and need skills to respond to them. For this reason, an HMS student-faculty interest group advocated for the inclusion of TIC in multiple areas of the HMS curriculum. Members of the group worked with faculty from the interviewing and communications skills component of the first-year clinical skills course to design a new learning session to provide first-year medical and dental students with explicit instruction in trauma-informed communication skills during the medical interview and a framework to screen for and respond to disclosures of trauma.In the curriculum at Harvard Medical School (HMS), medical and dental students interview patients as early as their first month of school and begin practicing physical examination the following month.MedEdPORTAL provided several examples of UME-level education around TIC including trauma-informed approaches to the physical exam,16 instruction on adverse childhood experiences,17 and trauma-informed approaches to the care of female sexual assault survivors.18 Several additional resources have been published recently regarding teaching medical students how to conduct IPV screening, but none that introduced TIC.21 This is the first session to teach first-year medical and dental students how to screen universally for diverse experiences of trauma and how to respond to disclosures of trauma in a trauma-informed manner.A review of 14We developed a 3.5-hour session to introduce TIC communication skills to all 164 first-year medical and dental students who matriculated during the 2018–2019 school year. Our group consisted of students and faculty at HMS in collaboration with multidisciplinary faculty at Brigham and Women's Hospital (BWH), including nurse practitioners and social workers. We presented the session within the interview and communication skills component of the first-year clinical skills course in January 2019. The session included three 1-hour segments: a live interview demonstration with a patient, a discussion session in small groups, and case-based role-plays. The session's design and implementation followed TIME principles of content and context: We codesigned all aspects of the session in collaboration with senior students and multidisciplinary clinicians with expertise in TIC; we empowered senior students to take on a variety of leadership roles; and we incorporated peer supports throughout the session.Groups of two or three student-facilitators and faculty-facilitators coled the small-group discussion and role-play sessions as described below. We assumed neither the student-facilitators nor faculty-facilitators had expertise in TIC. Before the session, we provided all facilitators with a guide  that sug22 The preparatory assignment included a series of didactic concept videos and simulated patient interview videos  model used in the HMS curriculum.w videos  totalingw videos  to proviThe first concept video defined trauma, identified its health effects, and introduced the theory of TIC . The sec1.○Introduction and didactic review (10 minutes)○Live interview demonstration (50 minutes)Large-group session (60 minutes)2.Break (15 minutes)3.Small-group discussion and reflection session (60 minutes)4.Break (15 minutes)5.○Student A as provider, Student B as patient (15 minutes)○Reflection (10 minutes)○Student B as provider, Student A as patient (15 minutes)○Reflection (10 minutes)Small-group role-plays (50 minutes)6.Wrap-up and postsession survey (10 minutes)7.Student-only healing space We structured the session as follows:The first hour began in a lecture hall with a 10-minute didactic review of TIC principles. Students then observed a clinician with expertise in TIC inquire about trauma, respond to the patient's disclosure, apply universal trauma education, and provide further counseling in a live interview demonstration. Following the observed interview, students had an opportunity to ask questions of the patient and/or clinician.The patient interviewed was known to one of our faculty and had previously expressed an interest in teaching medical students about trauma. To address the educational context and prepare for the session, the clinician interviewer and patient met twice beforehand, once by phone and once in person. In these meetings, our clinician interviewer obtained informed consent, reviewed what to expect during the session, previewed the questions that would be asked, and established strategies to use if the patient became distressed . The patient's primary care physician was also in the audience within the patient's line of sight for additional support. Following the session, one of our student-facilitators made themselves available to debrief with the patient.Following the large-group session, there was a 15-minute break, in which we encouraged students to seek guidance or additional support, as needed.Following this break, students moved into small groups. Small groups comprised six to eight students along with one to three faculty. These small groups had been working together for 5 months in the interview and communication skills course. Along with their usual faculty educators, most groups had additional facilitation from a TIC expert from a multidisciplinary pool recruited from four HMS-affiliated hospitals, as well as a third- or fourth-year medical student-facilitator. Student-facilitators led discussions and served as a peer support throughout the session. In the end, each group had at least one faculty-facilitator and one student-facilitator for the small-group discussions.To promote safety and attend to the educational context, facilitators began the reflection session by outlining expectations: confidentiality, assuming positive intent while attending to impact, and respect (no/limited technology). Next, facilitators encouraged students to share any reflections on the preparatory assignment or the live interview demonstration. Finally, facilitators asked students to identify how the provider in the live interview demonstration highlighted the principles of TIC. Groups discussed the assigned reflection questions, and in the remaining time, they created an agenda of topics and reflection questions associated with the video demonstrations for discussion.Following a second 15-minute break, students spent the last hour of the session in the same small groups with the same facilitators. Students participated in two case-based role-plays  designedIn a final effort to attend to the educational context and offer peer support, the medical students in our working group organized an optional, confidential, student-only healing space for first-year students immediately following the session. The healing space lasted for 1 hour and was facilitated by third- and fourth-year medical students with a background in TIC. It was open-ended, and student-facilitators invited first-year students to share reflections and reactions from the session.To assess the session's effectiveness, students completed pre- and postsession surveys. We embedded the surveys into the session's online course page. The presession survey asked students to assess their knowledge of TIC and their self-reported comfort with screening for and responding to disclosures of trauma, and to identify if they had received a disclosure of trauma before the session . The posnot at all comfortable, 100 = completely comfortable). We calculated means and standard deviations for students’ self-reported comfort scores and compared them by a two-tailed paired Student t-test analysis (α = .05). We analyzed free text for thematic content. Coauthor Taylor Brown manually read through all survey responses. For questions asking about the strengths and areas of improvement, Taylor Brown recorded how many responses commented on specific aspects of the session. For free-text items related to trauma disclosure, Taylor Brown recorded the types of trauma using prespecified categories: childhood abuse; sexual violence; physical violence, violence, or abuse toward a loved one; and structural violence. The postsession survey used a 5-point Likert scale to determine satisfaction with the session and effectiveness of the session at meeting learning objectives . We collected 5-month follow-up data on self-reported comfort and practice changes. The data collected from these surveys were part of educational quality improvement and therefore qualified for an institutional review board waiver based on institutional standards at HMS.We used Qualtrics software (Core XM) to collect presession, postsession, and follow-up survey data. We linked data through anonymous survey identifiers. We used 100-point scales for questions regarding comfort with screening for and responding to disclosures . For the 5-month follow-up data, 82 students completed the survey (50% response rate).not at all comfortable, 100 = completely comfortable), students’ self-reported baseline mean comfort levels with screening for trauma, responding to trauma disclosure, and counseling patients with positive IPV screens were 30 points (SD = 24), 35 points (SD = 25), and 25 points (SD = 22), respectively.Before the session, 34% of students reported having received at least one disclosure of trauma from a patient within the first 5 months of medical school. Types of disclosure included the following: sexual violence (29%); physical violence and abuse (25%); childhood sexual abuse (24%); and loss of a loved one (14%). Rated on a 100-point scale . Students’ mean comfort level with responding to disclosures increased to 55 points , and their mean comfort level with counseling patients who screened positive for IPV increased to 50 points . Students expressed high overall satisfaction with the session, with 87% of students reporting that the session was very effective or extremely effective at meeting the educational objectives. When asked about the most effective session elements, students identified in their free-text responses the live interview demonstration , the case-based role-play exercises (29%), the video demonstrations in the preparatory materials (8%), and the role of student and faculty facilitators (5%).After the intervention, students’ mean comfort level with trauma screening increased to 56 points , as did the observed increase in comfort with responding to disclosures . The number of students who received at least one disclosure of trauma nearly doubled to 64% at 5 months postintervention (10 months after matriculation) compared to 34% when the initial TIC session took place (5 months after matriculation). Of responding students, 73% reported changes in their clinical practices following the session. These changes included the use of standard language for trauma screening (30% of survey responses), including a ubiquity statement before discussing trauma , and minimizing the details shared about a trauma , also known as containment.The results of the follow-up survey administered 5 months after the intervention indicated that the observed increase in comfort with trauma screening persisted  of students received at least one trauma disclosure before receiving training on how to respond to such disclosures, and that 10 months after matriculation, the percentage of students that received at least one trauma disclosure nearly doubled to 64%.The development of this session relied heavily on student advocacy, which remained one of the session's greatest strengths. Through coproduction of course material with senior students and multidisciplinary TIC experts, we created a robust library of TIC curricular content. We recommend that all institutions seeking to develop a similar session coproduce it with students and multidisciplinary clinicians. Additionally, our session relied heavily on the HMS curricular structure in both recruiting faculty facilitators and creating cohesive small groups. For our intervention to be successfully implemented at other medical schools, educators would need to identify similarly cohesive small groups within their own curricular structure. Other institutions may also find it challenging to recruit and train the number of facilitators required for small-group sessions.24 Embodying or pretending to be a patient with lived experience of trauma can be distressing for students, particularly for students with their own experiences with adversity. Ideally, students should practice responding to disclosures with professional standardized patients. The next best alternative would be faculty and near-peer senior medical students assuming the patient role during practice role-plays. If neither of the aforementioned options are feasible, we encourage facilitators to empower small groups to choose the role-play methods that work best for their learners. One example of this would be to allow students to self-select into groups in which at least one student is comfortable in the patient role. Facilitators must be careful to normalize opting out of the patient role. Whatever the arrangement, students should be encouraged to verbally practice responding to disclosures. Finally, we have updated the role-plays to include standardized patient instructions. This will help to standardize the exchanges so that different students have similar learning experiences, as well as preventing participants from having to imagine how to disclose trauma.An important consideration in teaching TIC content is how to minimize distress for students. We know that teaching trauma content without a trauma-informed approach is potentially traumatic for students and faculty.This session served as an introduction to TIC not only for first-year students but also for many of our teaching faculty. Faculty development was key to the success of the initial session and will be key to the integration of TIC curricular content and context moving forward. As a result, we are currently designing a standardized faculty development curriculum in the format of asynchronous online modules to support our faculty in teaching TIC clinical skills. In the future, we hope to share these faculty development modules to assist with TIC content integration across other institutions.25 One main difference between screening and inquiry is that when pursuing trauma inquiry, the goal is not a disclosure of trauma. Trauma inquiry focuses on the symptoms and impacts of trauma experiences on one's health and well-being and seeks to prevent the retraumatization that may accompany the act of recounting a traumatic experience. Inquiry follows a tiered approach that allows patients to control whether and how much to disclose and only advises continued questioning when an immediate safety risk is present. Our original session used a similar open-ended question approach, but still called the technique screening. Therefore, the term screening is reflected in the teaching material and our survey results. Using the materials provided, instructors can nevertheless teach trauma inquiry. In subsequent iterations of the session, we have emphasized that disclosure is not the goal of trauma inquiry and have recommended screening only as a means of safety assessment, such as the case of ongoing IPV. Students are instructed to be mindful of how many times a patient must retell their story, avoid asking for details if not treating acutely, and encourage patients to disclose only as much as they feel comfortable sharing. As students’ skills progress, they can begin to explore the effects of trauma on a patient's health.One limitation of the session is that the field has moved away from trauma screening and now embraces trauma inquiry.Another limitation of our study is that student assessment relied on self-reported impressions without applying objective measures of learning, such as knowledge questions. Additionally, the survey items did not allow us to assess our stated learning objectives. Finally, for the questions asking students to report on their comfort with TIC clinical skills, we do not know the effect of using a 100-point scale as opposed to a more standard 5-point Likert scale. In future iterations of the session, we plan to use knowledge-based questions to assess each stated learning objective and convert 100-point scales to more standard 5-point Likert scales. We developed a TIC communication performance assessment  to assis14 We hope this work represents a step toward the creation of a trauma-informed educational context via trauma-informed session facilitation and explicit teaching on self-care and peer-support strategies for students facing the sequelae of trauma in their patients, their colleagues, and themselves.To our knowledge, this publication is the first to describe a session introducing first-year medical and dental students to a trauma-informed approach to obtaining the patient history, screening for and inquiring about trauma, and responding to trauma disclosures. This session represents one of several efforts at our institution to increase students’ understanding of the definition and health effects of trauma and the importance of adopting TIC as a universal approach to patient care.Facilitator Guide.docxTIC Introduction.mp4TIC Intimate Partner Violence and Screening.mp4Video Demonstrations.mp4Student Guide.docxTrauma-Informed Care Role-Play Cases.docxConversation Guide.docxPre-, Post-, and Follow-Up Surveys.docxTIC Communication Performance Assessment.docxAll appendices are peer reviewed as integral parts of the Original Publication.