Design and Modification of COVID-19 Case Investigation and Contact Tracing Interview Scripts Used by Health Departments Throughout the COVID-19 Pandemic.

OBJECTIVES: We sought to (1) document how health departments (HDs) developed COVID-19 case investigation and contact tracing (CI/CT) interview scripts and the topics covered, and (2) understand how and why HDs modified those scripts. DESIGN: Qualitative analysis of CI/CT interview scripts and in-depth key informant interviews with public health officials in 14 HDs. Collected scripts represent 3 distinct points (initial, the majority of which were time stamped May 2020; interim, spanning from September 2020 to August 2021; and current, as of April 2022). SETTING: Fourteen state, local, and tribal health jurisdictions and Centers for Disease Control and Prevention (CDC). PARTICIPANTS: Thirty-six public health officials involved in leading CI/CT from 14 state, local, and tribal health jurisdictions (6 states, 3 cities, 4 counties, and 1 tribal area). MAIN OUTCOME MEASURE: Interview script elements included in CI/CT interview scripts over time. RESULTS: Many COVID-19 CI/CT scripts were developed by modifying questions from scripts used for other communicable diseases. Early in the pandemic, scripts included guidance on isolation/quarantine and discussed symptoms of COVID-19. As the pandemic evolved, the length of scripts increased substantially, with significant additions on contact elicitation, vaccinations, isolation/quarantine recommendations, and testing. Drivers of script changes included changes in our understanding of how the virus spreads, risk factors and symptoms, new treatments, new variants, vaccine development, and adjustments to CDC's official isolation and quarantine guidance. CONCLUSIONS: Our findings offer suggestions about components to include in future CI/CT efforts, including educating members of the public about the disease and its symptoms, offering mitigation guidance, and providing sufficient support and resources to help people act on that guidance. Assessing the correlation between script length and number of completed interviews or other quality and performance measures could be an area for future study.

Adapting COVID-19 Contact Tracing Protocols to Accommodate Resource Constraints, Philadelphia, Pennsylvania, USA, 2021.

Because of constrained personnel time, the Philadelphia Department of Public Health (Philadelphia, PA, USA) adjusted its COVID-19 contact tracing protocol in summer 2021 by prioritizing recent cases and limiting staff time per case. This action reduced required staff hours to prevent each case from 21-30 to 8-11 hours, while maintaining program effectiveness.

Home-Based Testing and COVID-19 Isolation Recommendations, United States.

Using a nationally representative panel survey, we examined isolation behaviors among persons in the United States who had positive SARS-CoV-2 test results during January 2021-March 2022. Compared with persons who received provider-administered results, persons with home-based results had 29% (95% CI 5%-47%) lower odds of following isolation recommendations.

Use of High-Resolution Geospatial and Genomic Data to Characterize Recent Tuberculosis Transmission, Botswana.

Combining genomic and geospatial data can be useful for understanding Mycobacterium tuberculosis transmission in high-burden tuberculosis (TB) settings. We performed whole-genome sequencing on M. tuberculosis DNA extracted from sputum cultures from a population-based TB study conducted in Gaborone, Botswana, during 2012-2016. We determined spatial distribution of cases on the basis of shared genotypes among isolates. We considered clusters of isolates with ≤5 single-nucleotide polymorphisms identified by whole-genome sequencing to indicate recent transmission and clusters of ≥10 persons to be outbreaks. We obtained both molecular and geospatial data for 946/1,449 (65%) participants with culture-confirmed TB; 62 persons belonged to 5 outbreaks of 10-19 persons each. We detected geospatial clustering in just 2 of those 5 outbreaks, suggesting heterogeneous spatial patterns. Our findings indicate that targeted interventions applied in smaller geographic areas of high-burden TB identified using integrated genomic and geospatial data might help interrupt TB transmission during outbreaks.

Isolation and Quarantine for Coronavirus Disease 2019 in the United States, 2020-2022.

BACKGROUND: Public health programs varied in ability to reach people with coronavirus disease 2019 (COVID-19) and their contacts to encourage separation from others. For both adult case patients with COVID-19 and their contacts, we estimated the impact of contact tracing activities on separation behaviors from January 2020 until March 2022. METHODS: We used a probability-based panel survey of a nationally representative sample to gather data for estimates and comparisons. RESULTS: An estimated 64 255 351 adults reported a positive severe acute respiratory syndrome coronavirus 2 test result; 79.6% isolated for ≥5 days, 60.2% isolated for ≥10 days, and 79.2% self-notified contacts. A total of, 24 057 139 (37.7%) completed a case investigation, and 46.2% of them reported contacts to health officials. More adults who completed a case investigation isolated than those who did not complete a case investigation (≥5 days, 82.6% vs 78.2%, respectively; ≥10 days, 69.8% vs 54.8%; both P < .05). A total of 84 946 636 adults were contacts of a COVID-19 case patient. Of these, 73.1% learned of their exposure directly from a case patient; 49.4% quarantined for ≥5 days, 18.7% quarantined for ≥14 days, and 13.5% completed a contact tracing call. More quarantined among those who completed a contact tracing call than among those who did not complete a tracing call (≥5 days, 61.2% vs 48.5%, respectively; ≥14 days, 25.2% vs 18.0%; both P < .05). CONCLUSIONS: Engagement in contact tracing was positively correlated with isolation and quarantine. However, most adults with COVID-19 isolated and self-notified contacts regardless of whether the public health workforce was able to reach them. Identifying and reaching contacts was challenging and limited the ability to promote quarantining, and testing.

Experiences with COVID-19 case investigation and contact tracing: A qualitative analysis.

Case investigation and contact tracing (CI/CT) is a critical part of the public health response to COVID-19. Individuals' experiences with CI/CT for COVID-19 varied based on geographic location, changes in knowledge and guidelines, access to testing and vaccination, as well as demographic characteristics including age, race, ethnicity, income, and political ideology. In this paper, we explore the experiences and behaviors of adults with positive SARS-CoV-2 test results, or who were exposed to a person with COVID-19, to understand their knowledge, motivations, and facilitators and barriers to their actions. We conducted focus groups and one-on-one interviews with 94 cases and 90 contacts from across the United States. We found that participants were concerned about infecting or exposing others, which motivated them to isolate or quarantine, notify contacts, and get tested. Although most cases and contacts were not contacted by CI/CT professionals, those who were reported a positive experience and received helpful information. Many cases and contacts reported seeking information from family, friends, health care providers, as well as television news and Internet sources. Although participants reported similar perspectives and experiences across demographic characteristics, some highlighted inequities in receiving COVID-19 information and resources.

Estimated Cases Averted by COVID-19 Digital Exposure Notification, Pennsylvania, USA, November 8, 2020-January 2, 2021.

We combined field-based data with mathematical modeling to estimate the effectiveness of smartphone-enabled COVID-19 exposure notification in Pennsylvania, USA. We estimated that digital notifications potentially averted 7-69 cases/1,000 notifications during November 8, 2020-January 2, 2021. Greater use and increased compliance could increase the effectiveness of digital notifications.

Influence of COVID-19 for delaying the diagnosis and treatment of pulmonary tuberculosis-Tianjin, China.

Background: The COVID-19 pandemic has disrupted the diagnosis, treatment, and care for tuberculosis (TB). Delays in seeking TB care may result in increased community transmission and unfavorable treatment outcomes. We sought to understand the influence of the COVID-19 pandemic on the proportion of patients with TB who delayed seeking the diagnosis and care for TB and explore the reasons for their postponement. Methods: We surveyed a representative sample of outpatients treated for pulmonary TB from June to November 2020 using an anonymous standardized questionnaire. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) of factors associated with the postponement of TB care. We used routinely collected surveillance data to assess trends of TB reports before and after the emergence of COVID-19 (2017-2019 vs. 2020-2022) in Tianjin, China. Results: Among 358 participants who were diagnosed with pulmonary TB during the COVID-19 response, 61 (17%) postponed seeking TB diagnosis due to COVID-19, with 39 (64%) citing fear as the primary reason. Female sex (aOR:2.0; 95% CI: 1.1-3.7), previous antituberculosis treatment (aOR:3.2; 95%CI: 1.4-7.6), and TB diagnosis during the first-level response (aOR = 3.2, 1.7-6.2) were associated with the postponement. Among all 518 participants receiving antituberculosis treatment, 57 (11%) had postponed their regular healthcare visits due to COVID-19, 175 (34%) received no treatment supervision, and 32 (6%) experienced treatment interruption. Compared to 2017-2019, reported pulmonary TB declined by 36.8% during the first-level response to COVID-19, 23.5% during the second-level response, 14% during the third-level response in 2020, and 4.3% in 2021. Conclusion: The COVID-19 response reduced the number of people who sought and received diagnosis, treatment, and care for TB in Tianjin, China. Integrative programs to ensure access and continuity of TB services should be considered and dual testing for SARS-CoV-2 and M. tuberculosis may facilitate finding cases.

High Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Associated With Decreased Contact Tracing Effectiveness for Identifying Persons at Elevated Risk of Infection-Vermont.

Vermont contact tracing consistently identified people at risk for coronavirus disease 2019 (COVID-19). However, the prevalence ratio (PR) of COVID-19 among contacts compared with noncontacts when viral transmission was high (PR, 13.5 [95% confidence interval {CI}, 13.2-13.9]) was significantly less than when transmission was low (PR, 49.3 [95% CI, 43.2-56.3]).

Characterizing tuberculosis transmission dynamics in high-burden urban and rural settings.

Mycobacterium tuberculosis transmission dynamics in high-burden settings are poorly understood. Growing evidence suggests transmission may be characterized by extensive individual heterogeneity in secondary cases (i.e., superspreading), yet the degree and influence of such heterogeneity is largely unknown and unmeasured in high burden-settings. We conducted a prospective, population-based molecular epidemiology study of TB transmission in both an urban and rural setting of Botswana, one of the highest TB burden countries in the world. We used these empirical data to fit two mathematical models (urban and rural) that jointly quantified both the effective reproductive number, [Formula: see text], and the propensity for superspreading in each population. We found both urban and rural populations were characterized by a high degree of individual heterogeneity, however such heterogeneity disproportionately impacted the rural population: 99% of secondary transmission was attributed to only 19% of infectious cases in the rural population compared to 60% in the urban population and the median number of incident cases until the first outbreak of 30 cases was only 32 for the rural model compared to 791 in the urban model. These findings suggest individual heterogeneity plays a critical role shaping local TB epidemiology within subpopulations.

Isoniazid-associated pellagra during mass scale-up of tuberculosis preventive therapy: a case-control study.

BACKGROUND: Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population. METHODS: We did a matched case-control study to evaluate the association between daily, continuous isoniazid exposure and pellagra. We matched sequentially enrolled patients with pellagra each with four control participants by sex and age from referral dermatology centres in three IPT scale-up districts in Malawi (Lilongwe, Blantyre, and Zomba) to evaluate isoniazid as a risk for pellagra using multivariable conditional logistic regression. We established a community clinic referral system surrounding the dermatology clinic in each district to enhance case-finding and included all patients with pellagra, regardless of referral status. The primary outcome was dermatologist-diagnosed pellagra. We calculated the interval between isoniazid initiation and rash onset and assessed 30-day clinical outcomes after multi-B vitamin treatment containing 300 mg nicotinamide daily. FINDINGS: Between Feb 5 and Aug 9, 2019, we enrolled 197 patients with pellagra and 781 matched controls. Isoniazid exposure was associated with an increased risk of pellagra (adjusted odds ratio 42·6 [95% CI 13·3-136·6]). Significant covariates included HIV infection, referral status, food insecurity, underweight, excess alcohol consumption, and, among women, lactation. The median time from isoniazid initiation to rash onset was shorter during the season of food scarcity (5 months [IQR 3-7]) compared with the harvest season (9 months [8-11]; hazard ratio 7·2 [95% CI 3·2-16·2], log-rank p<0·0001). Those with isoniazid-associated pellagra who discontinued isoniazid and adhered to multi-B vitamin treatment showed 30-day clinical improvement. INTERPRETATION: Continuous IPT scale-up and the annual period of food scarcity both increased the risk of pellagra in Malawi. Use of shorter rifamycin-based regimens for tuberculosis prevention and food fortification in populations with undernutrition might reduce this risk. Niacin-containing multi-B vitamin co-administration with isoniazid as pellagra prevention is worth exploring further. FUNDING: This study was supported by the President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention under project 7173.

Tuberculosis attributed to transmission within healthcare facilities, Botswana-The Kopanyo Study.

OBJECTIVE: Healthcare facilities are a well-known high-risk environment for transmission of M. tuberculosis, the etiologic agent of tuberculosis (TB) disease. However, the link between M. tuberculosis transmission in healthcare facilities and its role in the general TB epidemic is unknown. We estimated the proportion of overall TB transmission in the general population attributable to healthcare facilities. METHODS: We combined data from a prospective, population-based molecular epidemiologic study with a universal electronic medical record (EMR) covering all healthcare facilities in Botswana to identify biologically plausible transmission events occurring at the healthcare facility. Patients with M. tuberculosis isolates of the same genotype visiting the same facility concurrently were considered an overlapping event. We then used TB diagnosis and treatment data to categorize overlapping events into biologically plausible definitions. We calculated the proportion of overall TB cases in the cohort that could be attributable to healthcare facilities. RESULTS: In total, 1,881 participants had TB genotypic and EMR data suitable for analysis, resulting in 46,853 clinical encounters at 338 healthcare facilities. We identified 326 unique overlapping events involving 370 individual patients; 91 (5%) had biologic plausibility for transmission occurring at a healthcare facility. A sensitivity analysis estimated that 3%-8% of transmission may be attributable to healthcare facilities. CONCLUSIONS: Although effective interventions are critical in reducing individual risk for healthcare workers and patients at healthcare facilities, our findings suggest that development of targeted interventions aimed at community transmission may have a larger impact in reducing TB.

Estimated COVID-19 Cases and Hospitalizations Averted by Case Investigation and Contact Tracing in the US.

Importance: Evidence of the impact of COVID-19 case investigation and contact tracing (CICT) programs is lacking, but policy makers need this evidence to assess the value of such programs. Objective: To estimate COVID-19 cases and hospitalizations averted nationwide by US states' CICT programs. Design, Setting, and Participants: This decision analytical model study used combined data from US CICT programs (eg, proportion of cases interviewed, contacts notified or monitored, and days to case and contact notification) with incidence data to model outcomes of CICT over a 60-day period (November 25, 2020, to January 23, 2021). The study estimated a range of outcomes by varying assumed compliance with isolation and quarantine recommendations. Fifty-nine state and territorial health departments that received federal funding supporting COVID-19 pandemic response activities were eligible for inclusion. Data analysis was performed from July to September 2021. Exposure: Public health case investigation and contact tracing. Main Outcomes and Measures: The primary outcomes were numbers of cases and hospitalizations averted and the percentage of cases averted among cases not prevented by vaccination and other nonpharmaceutical interventions. Results: In total, 22 states and 1 territory reported all measures necessary for the analysis. These 23 jurisdictions covered 42.5% of the US population (approximately 140 million persons), spanned all 4 US Census regions, and reported data that reflected all 59 federally funded CICT programs. This study estimated that 1.11 million cases and 27 231 hospitalizations were averted by CICT programs under a scenario where 80% of interviewed cases and monitored contacts and 30% of notified contacts fully complied with isolation and quarantine guidance, eliminating their contributions to future transmission. As many as 1.36 million cases and 33 527 hospitalizations could have been prevented if all interviewed cases and monitored contacts had entered into and fully complied with isolation and quarantine guidelines upon being interviewed or notified. Across both scenarios and all jurisdictions, CICT averted an estimated median of 21.2% (range, 1.3%-65.8%) of the cases not prevented by vaccination and other nonpharmaceutical interventions. Conclusions and Relevance: These findings suggest that CICT programs likely had a substantial role in curtailing the pandemic in most jurisdictions during the 2020 to 2021 winter peak. Differences in outcomes across jurisdictions indicate an opportunity to further improve CICT effectiveness. These estimates demonstrate the potential benefits from sustaining and improving these programs.

Overseas Treatment of Latent Tuberculosis Infection in US-Bound Immigrants.

Seventy percent of tuberculosis (TB) cases in the United States occur among non-US-born persons; cases usually result from reactivation of latent TB infection (LTBI) likely acquired before the person's US arrival. We conducted a prospective study among US immigrant visa applicants undergoing the required overseas medical examination in Vietnam. Consenting applicants >15 years of age were offered an interferon-γ release assay (IGRA); those 12-14 years of age received an IGRA as part of the required examination. Eligible participants were offered LTBI treatment with 12 doses of weekly isoniazid and rifapentine. Of 5,311 immigrant visa applicants recruited, 2,438 (46%) consented to participate; 2,276 had an IGRA processed, and 484 (21%) tested positive. Among 452 participants eligible for treatment, 304 (67%) initiated treatment, and 268 (88%) completed treatment. We demonstrated that using the overseas medical examination to provide voluntary LTBI testing and treatment should be considered to advance US TB elimination efforts.

Estimates of Cases and Hospitalizations Averted by COVID-19 Case Investigation and Contact Tracing in 14 Health Jurisdictions in the United States.

CONTEXT: The implementation of case investigation and contact tracing (CICT) for controlling COVID-19 (caused by SARS-CoV-2 virus) has proven challenging due to varying levels of public acceptance and initially constrained resources, especially enough trained staff. Evaluating the impacts of CICT will aid efforts to improve such programs. OBJECTIVES: Estimate the number of COVID-19 cases and hospitalizations averted by CICT and identify CICT processes that could improve overall effectiveness. DESIGN: We used data on the proportion of cases interviewed, contacts notified or monitored, and days from testing to case and contact notification from 14 jurisdictions to model the impact of CICT on cumulative case counts and hospitalizations over a 60-day period. Using the Centers for Disease Control and Prevention's COVIDTracer Advanced tool, we estimated a range of impacts by assuming either contacts would quarantine only if monitored or would do so upon notification of potential exposure. We also varied the observed program metrics to assess their relative influence. RESULTS: Performance by jurisdictions varied widely. Jurisdictions isolated between 12% and 86% of cases (including contacts that became cases) within 6 to 10 days after infection. We estimated that CICT-related reductions in transmission ranged from 0.4% to 32%. For every 100 remaining cases after other nonpharmaceutical interventions were implemented, CICT averted between 4 and 97 additional cases. Reducing time to case isolation by 1 day increased averted case estimates by up to 15 percentage points. Increasing the proportion of cases interviewed or contacts notified by 20 percentage points each resulted in at most 3 or 6 percentage point improvements in averted cases. CONCLUSIONS: We estimated that CICT reduced the number of COVID-19 cases and hospitalizations among all jurisdictions studied. Reducing time to isolation produced the greatest improvements in impact of CICT.

COVID-19 Contact Tracing Outcomes in Washington State, August and October 2020.

Introduction: Case investigation and contact tracing are important tools to limit the spread of SARS-CoV-2, particularly when implemented efficiently. Our objective was to evaluate participation in and timeliness of COVID-19 contact tracing and whether these measures changed over time. Methods: We retrospectively assessed COVID-19 case investigation and contact tracing surveillance data from the Washington State centralized program for August 1-31, 2020 and October 1-31, 2020. We combined SARS-CoV-2 testing reports with contact tracing data to compare completeness, reporting of contacts, and program timeliness. Results: For August and October respectively, 4,600 (of 12,521) and 2,166 (of 16,269) individuals with COVID-19 were referred to the state program for case investigation. Investigators called 100% of referred individuals; 65% (August) and 76% (October) were interviewed. Of individuals interviewed, 33% reported contacts in August and 45% in October, with only mild variation by age, sex, race/ethnicity, and urbanicity. In August, 992 individuals with COVID-19 reported a total of 2,584 contacts (mean, 2.6), and in October, 739 individuals reported 2,218 contacts (mean, 3.0). Among contacts, 86% and 78% participated in interviews for August and October. The median time elapsed from specimen collection to contact interview was 4 days in August and 3 days in October, and from symptom onset to contact interview was 7 days in August and 6 days in October. Conclusions: While contact tracing improved with time, the proportion of individuals disclosing contacts remained below 50% and differed minimally by demographic characteristics. The longest time interval occurred between symptom onset and test result notification. Improving elicitation of contacts and timeliness of contact tracing may further decrease SARS-CoV-2 transmission.

Use of SMS-linked electronic surveys for COVID-19 case investigation and contact tracing - Marin County, CA, USA.

OBJECTIVES: We sought to quantify the proportion of contacts reported by persons with COVID-19 through a short message service (SMS)-linked survey in comparison to the proportion of contacts reported during a follow-up phone-interview. We also sought to assess improvement in contact tracing timeliness associated with sending SMS-linked surveys. STUDY DESIGN: During December 4-15, 2020, persons identified as COVID-19 cases whose data was entered into Marin County's contact tracing database on even days received a SMS-linked survey and persons whose data was entered on odd days did not; all were called for case investigation and contact tracing. Chi-square test and Fisher's exact test were used to compare demographic data. Chi-square test was used to contrast categorical outcomes, and Wilcoxon's rank-sum test was used for continuous outcomes. RESULTS: Among 350 SMS-linked survey recipients, 85 (24%) responded and 4 (1%) reported contacts using the survey; an additional 303 contacts were reported during phone interviews. Without phone interviews, 99% of reported contacts would have been missed. There was no meaningful difference between study arms in the proportion of contacts notified within 48 h. CONCLUSIONS: This SMS-linked survey had low participation and was not useful for identifying contacts. Phone interviews remained crucial for COVID-19 contact tracing.

COVID-19 Case Investigation and Contact Tracing in the US, 2020.

Importance: Contact tracing is a multistep process to limit SARS-CoV-2 transmission. Gaps in the process result in missed opportunities to prevent COVID-19. Objective: To quantify proportions of cases and their contacts reached by public health authorities and the amount of time needed to reach them and to compare the risk of a positive COVID-19 test result between contacts and the general public during 4-week assessment periods. Design, Setting, and Participants: This cross-sectional study took place at 13 health departments and 1 Indian Health Service Unit in 11 states and 1 tribal nation. Participants included all individuals with laboratory-confirmed COVID-19 and their named contacts. Local COVID-19 surveillance data were used to determine the numbers of persons reported to have laboratory-confirmed COVID-19 who were interviewed and named contacts between June and October 2020. Main Outcomes and Measures: For contacts, the numbers who were identified, notified of their exposure, and agreed to monitoring were calculated. The median time from index case specimen collection to contact notification was calculated, as were numbers of named contacts subsequently notified of their exposure and monitored. The prevalence of a positive SARS-CoV-2 test among named and tested contacts was compared with that jurisdiction's general population during the same 4 weeks. Results: The total number of cases reported was 74 185. Of these, 43 931 (59%) were interviewed, and 24 705 (33%) named any contacts. Among the 74 839 named contacts, 53 314 (71%) were notified of their exposure, and 34 345 (46%) agreed to monitoring. A mean of 0.7 contacts were reached by telephone by public health authorities, and only 0.5 contacts per case were monitored. In general, health departments reporting large case counts during the assessment (≥5000) conducted smaller proportions of case interviews and contact notifications. In 9 locations, the median time from specimen collection to contact notification was 6 days or less. In 6 of 8 locations with population comparison data, positive test prevalence was higher among named contacts than the general population. Conclusions and Relevance: In this cross-sectional study of US local COVID-19 surveillance data, testing named contacts was a high-yield activity for case finding. However, this assessment suggests that contact tracing had suboptimal impact on SARS-CoV-2 transmission, largely because 2 of 3 cases were either not reached for interview or named no contacts when interviewed. These findings are relevant to decisions regarding the allocation of public health resources among the various prevention strategies and for the prioritization of case investigations and contact tracing efforts.

Early-phase scale-up of isoniazid preventive therapy for people living with HIV in two districts in Malawi (2017).

BACKGROUND: Isoniazid preventive therapy (IPT) against tuberculosis (TB) is a life-saving intervention for people living with HIV (PLHIV). In September 2017, Malawi began programmatic scale-up of IPT to eligible PLHIV in five districts with high HIV and TB burden. We measured the frequency and timeliness of early-phase IPT implementation to inform quality-improvement processes. METHODS AND FINDINGS: We applied a two-stage cluster design with systematic, probability-proportional-to-size sampling of six U.S. Centers for Disease Control and Prevention (CDC)-affiliated antiretroviral therapy (ART) centers operating in the urban areas of Lilongwe and Blantyre, Malawi (November 2017). ART clinic patient volume determined cluster size. Within each cluster, we sequentially sampled approximately 50 PLHIV newly enrolled in ART care. We described a quality-of-care cascade for intensive TB case finding (ICF) and IPT in PLHIV. PLHIV newly enrolled in ART care were eligibility-screened for hepatitis and peripheral neuropathy, as well as for TB disease using a standardized four-symptom screening tool. Among eligible PLHIV, the overall weighted IPT initiation rate was 70% (95% CI: 46%-86%). Weighted IPT initiation among persons aged <15 years (30% [95% CI: 12%-55%]) was significantly lower than among persons aged ≥15 years (72% [95% CI: 47%-89%]; Rao-Scott chi-square P = 0.03). HIV-positive children aged <5 years had a weighted initiation rate of only 13% (95% CI: 1%-79%). For pregnant women, the weighted initiation rate was 67% (95% CI: 32%-90%), similar to non-pregnant women aged ≥15 years (72% [95% CI: 49%-87%]). Lastly, 95% (95% CI: 92%-97%) of eligible PLHIV started ART within one week of HIV diagnosis, and 92% (95% CI: 73%-98%) of patients receiving IPT began on the same day as ART. CONCLUSIONS: Early-phase IPT uptake among adults at ART centers in Malawi was high. Child uptake needed improvement. National programs could adapt this framework to evaluate their ICF-IPT care cascades.