BackgroundAmong people with pulmonary tuberculosis (PTB), culture conversion (bacterial clearance) after two months of treatment is a good indicator of response. However, predictors of culture conversion at two months are difficult to define and can be context specific. In this study, we evaluated how two PTB severity grading metrics, the chest Xray (CXR) Score and the Bandim TBScore associate with and predict two-month culture conversion.MethodsThe cohort contained 718 index PTB cases enrolled in “The Kawempe Community Health Study (KCHS)”. We analyzed severity metrics, demographics, clinical, microbiological, radiological, household and behavioral data for their association with culture conversion using logistic regression.ResultsSixty-eight percent of participants culture converted at two months. The highest CXR Score category [odds ratio (OR) 0.51, 95% Confidence Interval (CI) 0.31, 0.84], smear grade at diagnosis [OR 0.43, 95% CI; 0.27, 0.64], pleural thickening [OR 0.43, 95% CI 0.18, 0.99] and current smoking [OR 0.31, 95% CI 0.09, 0.99] inversely associated with conversion. Both severity measures and the most parsimonious model poorly predicted culture conversion (all AUCs<0.70).ConclusionCXR Score, higher smear grade at diagnosis, pleural thickening and current tobacco smoking inversely associated with culture conversion. Our analyses indicated that all measures used provide limited utility for prediction.

Abstract Background U.S. vaccination rates fall short, with social vulnerabilities hindering access to preventive care. The influence of social determinants on vaccine uptake is a critical public health concern. This study explored the connection between the social vulnerability index (SVI), race, and vaccination rates for Influenza, SARS-CoV2, and RSV.Figure 1:Geospatial Distribution of Social Vulnerability Index and Vaccination Rates for Influenza, SARS-CoV-2, and RSV across Ohio Census Tracts with Patients to the University Hospital Healthcare Network. Geospatial representation of A) Public Social Vulnerability Index (SVI) for Ohio census tracts in 2020, B) Percentage of influenza vaccination, C) Percentage of SARS-CoV-2 vaccination, and D) Percentage of RSV vaccination for individuals aged 60 years and above. Figures B, C, and D show census tracts with a minimum of 10 patients presenting with mild to moderate respiratory infections to the University Hospital Healthcare network. The color scale for SVI ranges from 0 to 1, with the darkest red indicating the most vulnerable (SVI = 1) and the brightest cyan representing the least vulnerable (SVI = 0). The color scale for vaccination percentages spans from 0 to 100, with the darkest red denoting 0% vaccinated and the brightest cyan signifying 100% vaccinated. Methods We analyzed data from patients with acute respiratory infections treated at University Hospitals of Cleveland from October 2023 to April 2024. Patient demographics and vaccination statuses were collected from health records and matched with SVI census tract-level public data, which was geocoded and segmented into quartiles. We employed the Kruskal-Wallis and Pearson's Chi-squared tests for statistical analysis, and multivariate logistic regression adjusted for age and sex to assess vaccination odds. Results were depicted using geospatial methods to show the distribution of vaccinations and SVI across Ohio.Figure 2:Vaccinations Rates across race and social vulnerability index quantiles A comparison of vaccination rates for A) influenza, B) SARS-CoV-2, and C) RSV between White and Black populations across 10 quantiles of the Social Vulnerability Index (SVI). The SVI quantiles are represented on the x-axis, range from 0 to 1, with quantile 1 (SVI ≤ 0.2) representing the least vulnerable population and quantile 10 (SVI ≥ 0.8) representing the most vulnerable population. The y-axis shows the vaccination rates for each respective quantile. The color scheme used in the figure shows the White population in blue and the Black population in red. The summary statistics provide insights into the disparities in vaccination rates between White and Black individuals across varying levels of social vulnerability. Results The study analyzed a diverse population of 341,029 individuals, with 60% female and 38% male participants, and primarily consisted of white individuals (81%). Black individuals made up 14% of the population and were disproportionately represented in the highest vulnerability quartile (Q4) at 37%, which was significantly higher than the 3.2% in the lowest quartile (Q1). As the SVI quartile increased, vaccination rates decreased, particularly among Black individuals. Additionally, emergency visits for ARIs increased, while primary care visits decreased with higher SVI quartiles. The likelihood of vaccination decreased as the SVI quartile increased, especially among the Black group. The odds of receiving a flu vaccine were lower for Black individuals compared to White individuals in all SVI quartiles, with the greatest disparity in SVI Q5. Similarly, the odds of receiving the SARS-CoV-2 vaccine and the RSV vaccine were also lower for Black individuals compared to White individuals in all SVI quartiles. Detailed results are presented in the associated tables and figures.Table 1:Study Population Characteristics Across Social Vulnerability Index Quartiles Conclusion Socioeconomic vulnerability and race impact vaccination behaviors, emphasizing the need for tailored interventions to reduce disparities in vaccination rates among diverse populations.Table 2:Multivariate associations between Social Vulnerability Index (SVI) and Vaccination within White and Black Race Population Multivariate logistic regression models were used to evaluate the combined association between the SVI and race with the likelihood of vaccination for A) Influenza, B) SARS-CoV-2, and C) RSV. The models were adjusted for age and gender. The reference group for the combined race-SVI predictor was White individuals in the least vulnerable SVI quintile (Q1). Odds ratios, 95% confidence intervals, and p-values are presented for each race-SVI combination. Disclosures Elie Saade, MD, MPH, FIDSA, Janssen Global Services: Advisor/Consultant|Janssen Research and Development: Advisor/Consultant

Annual mass drug administration (MDA) is currently recommended for the local elimination of lymphatic filariasis (LF). Modeling studies of LF transmission suggest that conducting MDA twice a year could accelerate LF elimination. To test this idea, we compared the effects of 3 rounds of yearly MDA and 5 rounds of semiannual MDA using diethylcarbamazine with albendazole on LF infection measures in Papua New Guinea (PNG) across 2 treatment areas with high LF prevalence. From 2013 to 2018, we conducted 4 annual community surveys at 4 sentinel sites in each treatment area. We sampled 2,854 people at the start and 2,746, 2,339, and 2,569 people at 13, 27, and 40 months, respectively, with a similar number of participants in each area. Yearly MDA reduced microfilariae (Mf) prevalence from 24.0% at baseline (95% confidence interval [CI] 22.9-26.1%) to zero (CI, 0-0.4%) at 40 months. Similarly, semiannual MDA lowered Mf prevalence from 23.3% (CI, 21.4-25.4%) to 0.3% (CI, 0.1-0.7%). The circulating filarial antigen (CFA) prevalence decreased from 46.4% at baseline (CI, 43.5-49.3%) to 29.5% (CI, 26.9-32.3%) after 40 months with yearly treatment and from 53.4% (CI, 51.0-55.9%) to 35.2% (CI, 32.7-37.8%) with semiannual MDA. Using a generalized estimating equation model that accounted for age, sex, bednet use, and sentinel site, we found no significant difference in the effectiveness of the two treatment approaches (p = 0.845 for Mf and p = 0.332 for CFA). Therefore, annual and semiannual MDA were equally effective in reducing LF prevalence in this high-endemic setting.

Background WHO recommends two annual rounds of mass drug administration (MDA) with ivermectin, diethylcarbamazine, and albendazole (IDA) for lymphatic filariasis (LF) elimination in treatment naïve areas that are not co-endemic for onchocerciasis such as Papua New Guinea (PNG). Whether two rounds of MDA are necessary or sufficient and the optimal sampling strategies and endpoints for stopping MDA remain undefined. Methods and findings Two cross-sectional studies were conducted at baseline (N = 49 clusters or villages) and 12 months after mass drug administration (MDA) with IDA (N = 47 villages) to assess lymphatic filariasis (LF) by circulating filarial antigenemia (CFA) and microfilariae (Mf). Before MDA, children aged 6–9 years (N~50) and those ≥ 10 years (N~50) in each village were randomly sampled. Before MDA, the population mean prevalence of LF in East New Britain Province (ENBP), Papua New Guinea, was estimated using population proportionate sampling (PPS, N = 30) to be 59/2,561 (2.3%) CFA positive and 14/2,561 (0.6%) Mf positive. No children were Mf positive. However, LF infection was highly heterogeneous; 8 villages (26.7%) had a CFA prevalence >2%, and 7 villages (23.3%) had an Mf prevalence >1%. To identify sentinel villages with LF in areas under-sampled by PPS, 19 additional villages suspected to have LF were sampled, with 15 (79%) having >2% CFA prevalence and 7 (38%) >1% Mf (range 1–22%). Twenty-four villages were evaluated before and after MDA in age-matched adults ( ≥ 18 years). Treatment reduced CFA prevalence by 34% and Mf prevalence by 90%. Post-MDA model-based geostatistics efficiently selected an additional 23 villages, of which 20 (87%) had a CFA prevalence > 2%. None of these villages had >1% Mf. Post-MDA, two of four districts had no villages with >1% Mf. Conclusions Model-based geostatistics was more effective than PPS in sampling high-risk LF sites in a heterogeneous area. Low LF prevalence and partial reduction of CFA limit children’s effectiveness as sentinels. A single round of high-coverage MDA with IDA achieved elimination targets in low-prevalence villages in PNG. Higher-prevalence areas will need additional MDA rounds, which could be targeted to smaller evaluation units to cut costs. Trial registration Clinicaltrials.gov NCT04124250

This paper allays concerns that the commitment to protect fundamental rights in democracies has made them less effective in combatting COVID-19 than non-democracies. Our findings show that democracies have prevented more deaths per capita from COVID-19, controlling for other factors, than non-democracies. We demonstrate that the extent of political corruption drives this relationship.All regime types adopted pandemic mitigation measures but in countries with hybrid regimes, and to a lesser extent authoritarian regimes, corruption by government officials and public sector employees undermined mitigation efforts hindering infection control and treatment and thus contributing to deaths. Democracies have the lowest levels of corruption, and this helped them save lives. These conclusions are based on global statistical analyses and three mini-case studies. Theoretically, we advance the study of regime types’ impact by demonstrating how policy (non)implementation, not only policymaking, shapes societal outcomes.

Background Motor vehicle crashes (MVCs) are a leading cause of traumatic death and injury. Police traffic stops (PTS) are a common approach to enforcing motor vehicle laws intended to prevent MVCs. However, it is unclear which types of PTS are most effective. This study examined the relationship of PTS subtypes among municipal police patrols on non-interstate roads and MVCs and MVC-related deaths. Methods PTS subtype data were characterized from six North Carolina cities: Charlotte, Durham, Fayetteville, Greensboro, Raleigh, and Winston-Salem. The primary outcomes of this study were yearly non-interstate MVC and MVC-related death rates per 100 population. The data were analyzed as balanced time-series cross-sectional data. The statistical analysis accounted for time-dependent and city-dependent confounding. We used a two-way fixed effects model to analyze the relationship between PTS and MVC or MVC-related deaths. We also utilized the difference in difference (DID) analysis to analyze if the reduction of PTS following a 2012 policing administrative change in Fayetteville had an association with MVC or MVC-related deaths. Results We found no significant overall association between non-interstate PTS and MVCs (Coeff: -0.00006; p = 0.43) or MVC-related deaths (Coeff: -0.00011; p = 0.15). Panel regression suggested no significant relationship between MVCs and MVC-related deaths and PTS related to driving while impaired (p = 0.36), safe movement violation (p = 0.43), or seatbelt violations (p = 0.17). However, speed limit violations (Coeff: -0.00025; p = 0.032) and stop-light/sign violations (Coeff: -0.00147; p = 0.017) related to PTS significantly reduced MVC-related deaths. The DID regression showed no significant impact on MVCs (p = 0.924) or MVC-related deaths (0.706) before and after the police reform period. Conclusions The evidence regarding the absence of an overall association and any association with most PTS subtypes suggest that PTS are not effective for MVC death prevention. Policymakers may proceed with exploring modifications to policing efforts without detriments to public safety as defined by MVC and MVC-related deaths. Level of evidence Retrospective epidemiological study, level IV

Abstract Background Negative influenza-associated outcomes disproportionately impact non-White individuals. Targeted influenza vaccine coverage could improve outcomes in minority groups. This study examined the role of race-ethnicity and resource inequity in vaccine coverage. Methods We analyzed data from all outpatient visits at University Hospitals CMC from October 01, 2022 to February 28, 2023. Race, ethnicity, age, sex, income, home address, ICD diagnosis, and influenza immunization records were collected. Patients who received an influenza vaccine between July 01, 2022 and February 28, 2023 were considered immunized. A 9-digit patient zip code was used to obtain state Area Depravity Index (ADI) data provided by University of Wisconsin School of Medicine and Public Health. The state ADI ranges from 1 to 10, with group 1 being the least disadvantaged and 10 being the most disadvantaged. We used logistic regression analysis to estimate the odds for being vaccinated predicted by race-ethnicity, state ADI, age, and sex. Results Out of 301,572 hospitalizations, 59.0% were women, 81.2% were White non-Hispanic, 16.0% were Black non-Hispanic, and 2.7% were Hispanic. Black non-Hispanics were most disadvantaged with a mean State ADI of 7.54, followed by Hispanics at 5.64. White non-Hispanics were least disadvantaged with a mean State ADI of 3.99 (p< 0.001)(Table 1). Black non-Hispanics were disproportionately represented in the most disadvantaged areas (27.93%). Black non-Hispanics were 38% less likely to be vaccinated than White non-Hispanics. After ADI, sex, and age adjustment, Black non-Hispanics were 11% less likely to be vaccinated (OR: 0.89; 95% CI: 0.868 - 0.912). With each point increase in State ADI, vaccination rate decreased by 7% (OR: 0.93; 95% CI: 0.928 – 0.933)(Table 3). Regression analysis suggested significant interaction between race-ethnicity and State ADI. Influenza Vaccination by individual characteristics within overall population and race-ethnicity Influenza vaccination by race-ethnicity adjusting for State ADI, age, and sex Influenza vaccination by race-ethnicity adjusting for State ADI and sex, and stratified by age groups Conclusion This cross-sectional study found racial and ethnic disparities in rates of influenza vaccination. The effect of race-ethnicity on vaccination rate is dependent on ADI. These data identified subgroups on which to focus future influenza prevention efforts. The generalization of the study is limited and similar analysis from other areas and vaccines would be beneficial. Disclosures Elie Saade, MD, MPH, FIDSA, Envision Pharma: Speaker, Presenter|Johnson and Johnson: Speaker, Travel, Lodging|Protein Sciences Corp: Grant/Research Support|Sanofi Pasteur: Speaker, Travel and Lodging

Background Papua New Guinea (PNG) has a high burden of lymphatic filariasis (LF) caused by Wuchereria bancrofti , with an estimated 4.2 million people at risk of infection. A single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) has been shown to have superior efficacy in sustained clearance of microfilariae compared to diethylcarbamazine and albendazole (DA) in small clinical trials. A community-based cluster-randomised trial of DA versus IDA was conducted to compare the safety and efficacy of IDA and DA for LF in a moderately endemic, treatment-naive area in PNG. Methodology All consenting, eligible residents of 24 villages in Bogia district, Madang Province, PNG were enrolled, screened for W . bancrofti antigenemia and microfilaria (Mf) and randomised to receive IDA (N = 2382) or DA (N = 2181) according to their village of residence. Adverse events (AE) were assessed by active follow-up for 2 days and passive follow-up for an additional 5 days. Antigen-positive participants were re-tested one year after MDA to assess treatment efficacy. Principal findings Of the 4,563 participants enrolled, 96% were assessed for AEs within 2 days after treatment. The overall frequency of AEs were similar after either DA (18%) or IDA (20%) treatment. For those individuals with AEs, 87% were mild (Grade 1), 13% were moderate (Grade 2) and there were no Grade 3, Grade 4, or serious AEs (SAEs). The frequency of AEs was greater in Mf-positive than Mf-negative individuals receiving IDA (39% vs 20% p<0.001) and in Mf-positive participants treated with IDA (39%), compared to those treated with DA (24%, p = 0.023). One year after treatment, 64% (645/1013) of participants who were antigen-positive at baseline were re-screened and 74% of these participants (475/645) remained antigen positive. Clearance of Mf was achieved in 96% (52/54) of infected individuals in the IDA arm versus 84% (56/67) of infected individuals in the DA arm (relative risk (RR) 1.15; 95% CI, 1.02 to 1.30; p = 0.019). Participants receiving DA treatment had a 4-fold higher likelihood of failing to clear Mf (RR 4.67 (95% CI: 1.05 to 20.67; p = 0.043). In the DA arm, a significant predictor of failure to clear was baseline Mf density (RR 1.54; 95% CI, 1.09 to 2.88; p = 0.007). Conclusion IDA was well tolerated and more effective than DA for clearing Mf. Widespread use of this regimen could accelerate LF elimination in PNG. Trial registration Registration number NCT02899936 ; https://clinicaltrials.gov/ct2/show/NCT02899936 .

At the start of the Coronavirus Disease of 2019 (COVID-19) pandemic, the risk of cases in childcare programs was unknown. Thus, a rapid-response research approach was launched in Ohio childcare settings. Passive surveillance data from a state-operated incident reporting system were evaluated to estimate the number of COVID-19 cases from 15 August 2020 to 1 January 2021. Additionally, active surveillance with self-administered reverse transcriptase–polymerase chain reaction (RT-PCR) tests were conducted among staff at 46 childcare programs. Finally, six zoom-based focus groups with program administrators were used to gain feedback. Staff and children in childcare settings contributed 0.38% and 0.15% of the COVID-19 cases in Ohio during this timeframe, respectively. RT-PCR testing identified 3 unrecognized cases (0.88% of tests), and all occurred when the statewide positivity rate was >5%. Focus groups revealed that access to affordable cleaning supplies, masks, and reliable staffing were critical. Perhaps most importantly, we conclude that expanding the incident reporting system to include a childcare census would allow for the tracking of future health problems with highly valuable incidence rate estimations.

BACKGROUND:A single co-administered dose of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) has been shown to be safe and more efficacious for clearing Wuchereria bancrofti microfilariae than the standard two-drug regimen of diethylcarbamazine plus albendazole in clinical trials. However, the effectiveness of mass drug administration with the triple-drug regimen compared with the two-drug regimen is unknown. We compared the effectiveness of mass drug administration with the triple-drug and two-drug regimens for reducing microfilariae prevalence to less than 1% and circulating filarial antigen prevalence to less than 2%, levels that are unlikely to sustain transmission of lymphatic filariasis, in Papua New Guinea. METHODS:This open-label, cluster-randomised study was done in 24 villages in a district endemic for lymphatic filariasis in Papua New Guinea. Villages paired by population size were randomly assigned to receive mass drug administration with a single dose of the triple-drug oral regimen of ivermectin (200 μg per kg of bodyweight) plus diethylcarbamazine (6 mg per kg of bodyweight) plus albendazole (400 mg) or a single dose of the two-drug oral regimen of diethylcarbamazine (6 mg per kg of bodyweight) plus albendazole (400 mg). This is a follow-on study of a previously reported safety study (ClinicalTrials.govNCT02899936). All residents aged 5 years or older and non-pregnant women were asked to participate. After cross-sectional night blood microfilariae and circulating filarial antigen surveys, mass drug administration was provided at baseline and repeated 12 months later. The primary outcomes were mean prevalence of microfilariae and circulating filarial antigen at 12 months and 24 months, assessed in all residents willing to participate at each timepoint. This study is registered with ClinicalTrials.gov, NCT03352206. FINDINGS:Between Nov 18, 2016, and May 26, 2017, 4563 individuals were enrolled in 24 clusters; 12 clusters (2382 participants) were assigned to the triple-drug regimen and 12 clusters (2181 participants) to the two-drug regimen. Mean drug ingestion rates (of residents aged ≥5 years) were 66·1% at baseline and 63·2% at 12 months in communities assigned to the triple-drug regimen and 65·9% at baseline and 54·9% at 12 months in communities assigned to the two-drug regimen. Microfilariae prevalence in the triple-drug regimen group decreased from 105 (4·4%) of 2382 participants (95% CI 3·6-5·3) at baseline to nine (0·4%) of 2319 (0·1-0·7) at 12 months and four (0·2%) of 2086 (0·1-0·5) at 24 months. In the two-drug regimen group, microfilariae prevalence decreased from 93 (4·3%) of 2181 participants (95% CI 3·5-5·2) at baseline to 29 (1·5%) of 1963 (1·0-2·1) at 12 months and eight (0·4%) of 1844 (0·2-0·9) at 24 months (adjusted estimated risk ratio 4·5, 95% CI 1·4-13·8, p=0·0087, at 12 months; 2·9, 95% CI 1·0-8·8, p=0·058, at 24 months). The prevalence of circulating filarial antigen decreased from 523 (22·0%) of 2382 participants (95% CI 20·3-23·6) at baseline to 378 (16·3%) of 2319 (14·9-17·9) at 12 months and 156 (7·5%) of 2086 (6·4-8·7) at 24 months in the triple-drug regimen group and from 489 (22·6%) of 2168 participants (20·7-24·2) at baseline to 358 (18·2%) of 1963 (16·7-20·1) at 12 months and 184 (10·0%) of 1840 (8·7-11·5) at 24 months in the two-drug regimen group; after adjustment, differences between groups were not significant. INTERPRETATION:Mass administration of the triple-drug regimen was more effective than the two-drug regimen in reducing microfilariae prevalence in communities to less than the target level of 1%, but did not reduce circulating filarial antigen prevalence to less than 2%. These results support the use of mass drug administration with the triple-drug regimen to accelerate elimination of lymphatic filariasis. FUNDING:Bill & Melinda Gates Foundation.

We performed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antinucleocapsid IgG testing on 5,557 healthcare providers and found a seroprevalence of 3.9%. African Americans were more likely to test positive than Whites, and HCWs with household exposure and those working on COVID-19 cohorting units were more likely to test positive than their peers.

Despite the narratives of authoritarian states, the concerns of journalists and public intellectuals in democracies, and the results of some early studies, this paper shows that democracies fare no worse than authoritarian regimes in combating the Covid-19 pandemic. Democracy is not associated with higher Covid-19 death rates, nor is it associated with lower vaccination rates. Moreover, among many democratic countries, high levels of key democratic components -such as fundamental rights and impartial administration—seem to help prevent deaths and boost vaccination rates. These conclusions are based on statistical analyses of democracy components, as measured by International IDEA’s Global State of Democracy (GSoD) Indices, and the reported Covid-19 death rates and Covid-19 vaccination rates in all countries of the world with a population of at least one million people.

To what extent do particular regime types provide tangible benefits? During this era of declining faith in democracy globally and assertive alternatives to democracy, identifying democracy’s tangible benefits is particularly important. This paper reveals a benefit of democracy, relative to other regime types, in one issue area—epidemics. The paper demonstrates that democracy, compared to other regime types, lowers epidemic deaths in countries by approximately 70 percent, ceteris paribus. This result is driven by particular democratic components—free and fair elections and legislative and executive constraints on the executive—and by democracy at both the national and local levels. These findings support our argument that democracies’ relative success in reducing epidemics deaths is due to the incentives for and constraints on executives at different levels of government to act rapidly in pursuit of the public good. Our novel methodological approaches of investigating democracy’s components and different levels of government allows us to begin to develop a theoretical framework of regime types’ effects in different issue areas. These approaches generate more useful advice to policymakers and practitioners: they need guidance about which democratic institutions and practices and which levels of government to invest in for the greatest benefits.

Following the scale-up of intervention efforts, malaria burden has decreased dramatically in Solomon Islands (SI). Submicroscopic and asymptomatic Plasmodium vivax infections are now the major challenge for malaria elimination in this country. Since children have higher risk of contracting malaria, this study investigated the dynamics of Plasmodium spp. infections among children including the associated risk factors of residual P. vivax burden.

BACKGROUND:The Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. Recent trials have shown that a single-dose, triple-drug treatment (ivermectin with diethylcarbamazine and albendazole [IDA]) is superior to a two-drug combination (diethylcarbamazine plus albendazole [DA]) that is widely used in LF elimination programs. This study was performed to assess the safety of IDA and DA in a variety of endemic settings.METHODS AND FINDINGS:Large community studies were conducted in five countries between October 2016 and November 2017. Two studies were performed in areas with no prior mass drug administration (MDA) for filariasis (Papua New Guinea and Indonesia), and three studies were performed in areas with persistent LF despite extensive prior MDA (India, Haiti, and Fiji). Participants were treated with a single oral dose of IDA (ivermectin, 200 μg/kg; diethylcarbamazine, 6 mg/kg; plus albendazole, a fixed dose of 400 mg) or with DA alone. Treatment assignment in each study site was randomized by locality of residence. Treatment was offered to residents who were ≥5 years of age and not pregnant. Adverse events (AEs) were assessed by medical teams with active follow-up for 2 days and passive follow-up for an additional 5 days. A total of 26,836 persons were enrolled (13,535 females and 13,300 males). A total of 12,280 participants were treated with DA, and 14,556 were treated with IDA. On day 1 or 2 after treatment, 97.4% of participants were assessed for AEs. The frequency of all AEs was similar after IDA and DA treatment (12% versus 12.1%, adjusted odds ratio for IDA versus DA 1.15, 95% CI 0.87-1.52, P = 0.316); 10.9% of participants experienced mild (grade 1) AEs, 1% experienced moderate (grade 2) AEs, and 0.1% experienced severe (grade 3) AEs. Rates of serious AEs after DA and IDA treatment were 0.04% (95% CI 0.01%-0.1%) and 0.01% (95% CI 0.00%-0.04%), respectively. Severity of AEs was not significantly different after IDA or DA. Five of six serious AEs reported occurred after DA treatment. The most common AEs reported were headache, dizziness, abdominal pain, fever, nausea, and fatigue. AE frequencies varied by country and were higher in adults and in females. AEs were more common in study participants with microfilaremia (33.4% versus 11.1%, P < 0.001) and more common in microfilaremic participants after IDA than after DA (39.4% versus 25.6%, P < 0.001). However, there was no excess of severe or serious AEs after IDA in this subgroup. The main limitation of the study was that it was open-label. Also, aggregation of AE data from multiple study sites tends to obscure variability among study sites.CONCLUSIONS:In this study, we observed that IDA was well tolerated in LF-endemic populations. Posttreatment AE rates and severity did not differ significantly after IDA or DA treatment. Thus, results of this study suggest that IDA should be as safe as DA for use as a MDA regimen for LF elimination in areas that currently receive DA.TRIAL REGISTRATION:Clinicaltrials.gov registration number: NCT02899936.